PMID- 8280521
TI  - Balloon dilatation (valvoplasty) as first line treatment for severe stenosis of
      the aortic valve in early infancy: medium term results and determinants of
      survival.
AB  - OBJECTIVE: To assess the results of balloon dilatation of the aortic valve as
      first line treatment for infants presenting in the first two months of life with
      cardiac failure caused by severe aortic stenosis. DESIGN: A prospective study of
      all such infants presenting to a single centre over a three year period.
      PATIENTS: Of 14 consecutive infants aged < 2 months presenting with heart failure
      due to severe stenosis of the aortic valve, 12 underwent balloon dilatation of
      the valve. Two infants with hypoplastic left heart syndrome were excluded. Six
      patients had other significant cardiac malformations, nine had endocardial
      fibroelastosis. Four infants were moribund at presentation. INTERVENTIONS:
      Balloon dilatation was performed through the femoral artery under general
      anaesthetic, with heparin and antibiotic prophylaxis. Maximum inflated balloon
      size was selected as equal to or slightly less than the diameter of the aortic
      valve measured echocardiographically. In two infants balloon dilatation of
      coexistent severe coarctation was performed at the same time. RESULTS: Dilatation
      was achieved in all cases. Early survival rate (up to one month) was 75%; 50%
      survive up to three years. The two deaths occurring < 24 hours after dilatation
      probably related to the infants' poor condition at presentation and the presence
      of significant left ventricular hypoplasia. The other early death was due to
      severe mitral regurgitation from papillary muscle dysfunction. All later deaths
      were related to associated malformations. The difference in left ventricular size
      (diameter and length) measured echocardiographically at presentation between
      survivors and those that died is significant (p < or = 0.002). 83% of deaths
      occurred in infants with associated malformations. Cusp perforation occurred in
      one infant, which may have contributed to this patient's death. Left ventricular
      perforation and cardiac tamponade were treated successfully by prompt
      pericardiocentesis in another. CONCLUSIONS: Balloon dilatation of the aortic
      valve is an acceptable first line treatment for neonates with severe symptomatic
      stenosis of the aortic valve. Outcome depends principally on left ventricular
      size and on the presence, severity, and timing of treatment of associated
      malformations. Severe endocardial fibroelastosis was not a risk factor for early
      death but may have implications for long term survival. The survival rate for
      this high risk group might be improved by a stratified approach where patients
      with adequate left ventricular size have balloon dilatation whereas those with
      severe ventricular hypoplasia are managed like patients with the hypoplastic left
      heart syndrome.

PMID- 8280522
TI  - Recurrence of Churg Strauss vasculitis in a transplanted heart.

PMID- 8280523
TI  - Vascular access in previously catheterised children and adolescents: a
      prospective study of 131 consecutive cases.
AB  - BACKGROUND: Vascular access for cardiac catheterisation of children and young
      adults who have had previous catheter procedures is often difficult. OBJECTIVE:
      To assess the influence of age at and type and technique of previous cardiac
      catheterisation on the ease of vascular access for subsequent study of paediatric
      and adolescent patients. SETTING: Tertiary referral centre for paediatric
      cardiology. PATIENTS: 478 Consecutive patients aged 1 day to 19 years undergoing
      cardiac catheterisation over a 12 month period, including 131 patients who had
      had previous catheterisation(s). METHODS: Prospective study, recording for each
      patient the age, weight, diagnosis, vascular access (artery, vein, or both),
      vessels eventually catheterised, access time, total duration of the procedure,
      and details of any previous catheter studies. RESULTS: Of 131 patients who had
      had previous catheterisations, 80 (61%) had been studied once previously, 38
      (29%) twice, and 13 (10%) on three or more occasions. The right femoral vessels
      were cannulated without difficulty in 72 cases (55%). Elective cannulation of
      left femoral vessels (because of scar tissue on the right side) or upper body
      vessels was undertaken in 18 cases (14%). Problems cannulating the right femoral
      vessels were encountered in 41 cases (31%); the vein was blocked in 29, the
      artery in six and the femoral veins were blocked bilaterally in six cases. The
      mean (SD) access time was significantly prolonged in these 41 children (41(18) v
      21(13) minutes, p < 0.001) as was total duration of the procedure (116(31) v
      94(34) minutes, p < 0.001). Children who had had a saphenous vein cut down as
      neonates subsequently had a blocked ipsilateral femoral vein in 10/15 cases
      (67%). Risk factors for problematic cannulation also included a higher number of
      previous catheterisation procedures. CONCLUSIONS: Difficulties with vascular
      access are common in children and adolescents who have had previous cardiac
      catheterisations. In those who have had cut down or multiple previous studies,
      elective entry to the left femoral vessels should be undertaken and procedure
      time may be prolonged. Such cases should therefore be performed under general
      anaesthesia.

PMID- 8280524
TI  - Intercoronary collateral flow detected by Doppler colour flow mapping is an
      additional diagnostic sign in children with anomalous origin of the left coronary
      artery from the pulmonary artery.
AB  - Intercoronary collateral flow within septal collaterals was detected by colour
      coded Doppler echocardiography in three children with anomalous origin of the
      left coronary artery from the pulmonary artery. In each of the three patients
      angiography confirmed the presence of septal collaterals.

PMID- 8280525
TI  - Amyloid, thrombosis, and acute myocardial infarction in association with a
      bicuspid aortic valve.
AB  - A 34 year old man presented with an inferior non-Q-wave myocardial infarction.
      Echocardiography showed a bicuspid aortic valve with aortic outflow obstruction.
      Left coronary cusp morphology was normal but the right coronary cusp was grossly
      distorted and replaced by a mobile echodense mass encroaching upon the aortic
      valve orifice. The aortic valve was replaced and pathological analysis of the
      excised valve showed primary amyloid infiltration of the right coronary cusp but
      a normal left coronary cusp. The mass adherent to the right coronary leaflet had
      the histological appearances of organised thrombus and this was assumed to be the
      source of coronary embolism. This is the first reported case of primary valvar
      amyloid presenting with clinical sequelae and it illustrates the need for careful
      clinical assessment in young patients presenting with acute ischaemic syndromes.

PMID- 8280526
TI  - Transient cortical blindness after coronary angiography.
AB  - Transient visual loss lasting three days developed after transfemoral coronary
      angiography in a 62 year old man. Computed tomography (CT) showed bilateral
      leakage of contrast medium into the occipital cortex. A repeat CT scan after his
      sight recovered showed clearance of contrast with no underlying infarction. A
      breakdown of the blood-brain barrier with direct neurotoxicity of the contrast
      media seemed to be the cause of these neurological changes after coronary
      angiography which apparently have not been reported before.

PMID- 8280527
TI  - Histoplasma endocarditis on a stenosed aortic valve presenting as dysphagia and
      weight loss.
AB  - A 40-year-old man with aortic stenosis and disseminated histoplasmosis did not
      respond to treatment with itraconazole. Though there was no haemodynamic
      deterioration, valvar regurgitation, or embolic phenomena a presumptive diagnosis
      of infective endocarditis was made. This was confirmed at aortic valve
      replacement. Antifungal treatment was continued for 18 months after valve
      replacement and serological tests for Histoplasma became progressively more
      negative during a three year follow up.

PMID- 8280528
TI  - Out-of-hospital resuscitation in East Sussex: 1981 to 1989.
AB  - OBJECTIVE: To assess the impact of extended training in advanced life support on
      the outcome of resuscitation. DESIGN: Analysis of the successful resuscitations
      from 1981 to 1989. SETTING: Brighton and East Sussex. RESULTS: 248 patients were
      resuscitated from cardiac or respiratory arrest in the community and subsequently
      survived to leave hospital. Their mean age was 64 years and one year survival was
      77%. In most cases the cause of collapse was cardiac but 38 (15%) suffered a
      respiratory arrest. In 140 of the successful resuscitations (56%) collapse
      occurred before the arrival of the ambulance. Basic life support, with
      ventilation and chest compression where necessary, was sufficient to revive 35
      (14%) of the patients. Defibrillation was also required in 107 patients (43%),
      and in a further 106 patients (43%) who had prolonged cardiorespiratory arrest
      requiring endotracheal intubation and the use of several drugs. Review of
      ambulance forms and case notes showed that in 87 cases (35%) the abilities of the
      paramedical ambulance staff in advanced resuscitation techniques contributed
      decisively to the success of resuscitation. These skills are illustrated by eight
      case reports. CONCLUSIONS: Extended training for ambulance staff increases the
      likelihood of successful resuscitation from out-of-hospital cardiopulmonary
      arrest. Though instruction in defibrillation must have the highest priority, full
      paramedical training can bring appreciable additional benefits.

PMID- 8280529
TI  - Intractable chest pain in cardiomyopathy: treatment by a novel technique of
      cardiac cryodenervation with quantitative immunohistochemical assessment of
      success.
AB  - A novel method of cardiac denervation by cryoablation has been developed
      experimentally. The technique uses liquid nitrogen delivered under pressure to
      ablate the principal sources of cardiac innervation--namely, the adventitia
      surrounding the aorta, pulmonary arteries, and veins. The technique has been
      verified experimentally both in vivo by physiological means and in vitro by
      quantitative immunohistochemistry and the measurement of myocardial noradrenaline
      concentrations. A 35 year old woman presented with intractable precordial pain,
      normal epicardial coronary arteries, and hypertrophic cardiomyopathy. Her
      symptoms were refractory to maximal medical treatment and she was thought to be
      unsuitable for either conventional myocardial revascularisation,
      autotransplantation, or allografting with the concomitant risk of transplant
      coronary artery disease. She therefore underwent cardiac denervation by the
      method developed in the laboratory. There was quantitative immunohistochemical
      evidence of extrinsic cardiac denervation associated with a considerable
      improvement in her symptoms. This improvement persisted during a follow up period
      of over 16 months.

PMID- 8280530
TI  - Ventricular pacing from the coronary sinus of a patient with a Fontan
      circulation.
AB  - Permanent pacing of the left ventricle was achieved by transvenous implantation
      of a steroid-eluting electrode into the coronary sinus in a patient who had
      undergone a Fontan operation. This approach to endocardial pacemaker implantation
      is potentially of considerable value in patients who do not have transvenous
      access to the right ventricle.

PMID- 8280531
TI  - Results of a comparative study of low energy direct current with radiofrequency
      ablation in patients with the Wolff-Parkinson-White syndrome.
AB  - OBJECTIVE: To compare two new power sources for catheter ablation in patients
      with the Wolff-Parkinson-White syndrome. DESIGN: 120 consecutive patients with
      accessory pathways had catheter ablation. Low energy direct current (DC) was used
      in the first 60 patients and radio-frequency current in the next 60 patients.
      SETTING: Electrophysiological laboratory of a large heart institute. PATIENTS: 72
      men and 48 women (mean (SD) age 35 (14) years (range 9-75)). The accessory
      pathways were in the left free wall in 73 patients. They were posteroseptal in 35
      patients, in the right free wall in five, and anteroseptal in seven. There was no
      significant difference in the clinical or electrophysiological variables between
      the two ablation groups. RESULTS: Catheter ablation with low energy direct
      current was successful in 55/60 patients (92%) and radiofrequency energy was
      successful in 52/60 patients (87%). Low energy direct current was also successful
      in four of the eight patients in whom radiofrequency ablation had failed.
      Radiofrequency ablation was successful in two of the five patients in whom low
      energy direct current ablation had failed. The mean (SD) procedure and
      fluoroscopy times for successful ablation were 3.2 (1.5) h and 61 (40) min
      respectively. These times were similar for both power sources. Accessory pathway
      conduction recurred in 17 patients (28%) who had low energy direct current and
      four patients (7%) who received radiofrequency energy (p < 0.004). All patients
      with recurrence of an accessory pathway had successful re-ablation. CONCLUSIONS:
      Both new power sources successfully ablated accessory pathways, (overall success
      rate 94% (113/120 patients)). Radiofrequency ablation, however, did not require
      general anaesthesia and was associated with a significantly lower rate of
      recurrence of accessory pathway conduction. Therefore radiofrequency should be
      used initially for ablation. Low energy direct current may be most useful as a
      back-up in patients in whom radiofrequency ablation fails.

PMID- 8280532
TI  - Antibiotic prophylaxis for cardiac surgery: current United Kingdom practice.
AB  - A questionnaire was sent to 120 United Kingdom cardiac surgeons to ask for
      information on their use of prophylactic antibiotics in adult cardiac surgical
      patients. Data on type and duration of antibiotic were specifically sought. The
      response rate was 91%. All respondents used prophylactic antibiotics: 32% used
      single agents (second and third generation cephalosporins were the most commonly
      used) and 68% used either two (89%) or three (11%) antibiotics in combination.
      The total duration of prophylactic antibiotic treatment was less than 48 hours
      for 89% of respondents. Single dose antibiotics were used by only 6%. The use of
      prophylactic antibiotics has changed in the past few years, with a trend away
      from combinations of antibiotics to single agents. The duration of use of
      antibiotics has shortened and the use of single dose agents has increased.

PMID- 8280533
TI  - How John Parkinson did the post mortem on Sir James Mackenzie.

PMID- 8280534
TI  - Permanent pacing after cardiac transplantation.

PMID- 8280535
TI  - Spontaneous ventricular defibrillation.

PMID- 8280536
TI  - Cost effectiveness of prophylaxis in dental practice to prevent infective
      endocarditis.

PMID- 8280537
TI  - Choice of route for insertion of temporary pacing wires: recommendations of the
      Medical Practice Committee and Council of the British Cardiac Society.

PMID- 8280538
TI  - Awareness during total i.v. anaesthesia.
AB  - Five cases of awareness have been identified during total i.v. anaesthesia with
      mechanically controlled ventilation and neuromuscular block. Two of the cases
      resulted from inability to deliver the target dose of anaesthetics, while the
      patient's need for anaesthetics was greater than anticipated in three. It is
      concluded that all cases were caused primarily by lack of experience, and could
      have been prevented. These five cases occurred in experience from approximately
      2500 patients anaesthetized with this technique. Pre-, per- and postoperative
      data on the most recent 1727 patients have been entered into a database and may
      serve to provide data on the group of patients in whom the five cases of
      awareness occurred.

PMID- 8280539
TI  - Re-expansion of atelectasis during general anaesthesia: a computed tomography
      study.
AB  - Formation of atelectasis is one mechanism of impaired gas exchange during general
      anaesthesia. We have studied manoeuvres to re-expand such atelectasis in 16
      consecutive, anaesthetized adults with healthy lungs. In group 1 (10 patients),
      the lungs were inflated stepwise to an airway pressure (Paw) of 10, 20, 30 and 40
      cm H2O. In group 2 (six patients), three repeated inflations up to Paw = 30 cm
      H2O were followed by one inflation to 40 cm H2O. Atelectasis was assessed by
      analysis of computed x-ray tomography (CT). In group 1 the mean area of
      atelectasis in the CT scan at the level of the right diaphragm was 6.4 cm2 at Paw
      = 0 cm H2O, 5.9 cm2 at 20 cm H2O, 3.5 cm2 at 30 cm H2O and 0.8 cm2 at 40 cm H2O.
      A Paw of 20 cm H2O corresponds approximately to inflation with twice the tidal
      volume. In group 2 the mean area of atelectasis was 9.0 cm2 at Paw = 0 cm H2O and
      4.2 cm2 after the first inflation to 30 cm H2O. Repeated inflations did not add
      to re-expansion of atelectasis. The final inflation (Paw = 40 cm H2O) virtually
      eliminated the atelectasis. We conclude that, after induction of anaesthesia, the
      amount of atelectasis was not reduced by inflation of the lungs with a
      conventional tidal volume or with a double tidal volume ("sigg"). An inflation to
      vital capacity (Paw = 40 cm H2O), however, re-expanded virtually all atelectatic
      lung tissue.

PMID- 8280540
TI  - Fresh gas flow requirements during spontaneous ventilation: fresh gas flow to
      total ventilation ratio or ml kg-1 min-1?
AB  - Both the performance of breathing systems and recommendations for the fresh gas
      flows to be used in patients breathing spontaneously can be expressed in ml kg-1
      min-1 or fresh gas: total ventilation ratio (VF:VE). We have examined the
      relationship between these two descriptions. The data of 106 subjects (awake
      volunteers and anaesthetized patients) were retrieved from the archives of
      previous work performed in our department. The two methods of describing the
      requisite fresh gas produced different results, with correlation coefficients (r)
      between the methods of r = 0.69 and r = 0.49 for the awake and anaesthetized
      groups, respectively. The results of the multiple regression models suggest that
      both baseline total ventilation and body weight may be used to predict the fresh
      gas flow requirements, but residual analysis did not discriminate which method
      was a better predictor.

PMID- 8280541
TI  - Effect of cricoid pressure on ease of insertion of the laryngeal mask airway.
AB  - We have evaluated the effects of cricoid pressure on laryngeal mask airway (LMA)
      insertion after an elective rapid sequence induction in 100 patients allocated
      randomly to two groups. An attempt was made to insert the LMA after application
      of cricoid pressure in one group and with no pressure in the other. The
      anaesthetist was blinded to the application of cricoid pressure. Insertion was
      successful in 45 of 50 patients in the cricoid pressure group and in 49 of 50
      patients in the non-cricoid group (P < 0.1) We discuss the implications of these
      findings for failed intubation in the nonfasted patient.

PMID- 8280542
TI  - Radiological examination of the intrathecal position of microcatheters in
      continuous spinal anaesthesia.
AB  - There have been few studies of the intrathecal position of spinal catheters in
      continuous spinal anaesthesia. This prospective study was designed to examine
      radiologically the intrathecal position of 28-gauge spinal catheters. We studied
      the entry into the subarachnoid space and the intrathecal position of 68 spinal
      catheters. In 50%, the catheters passed in a cranial direction, in 34% the
      catheters remained at the level of the puncture site and in 16% the catheters
      were directed caudally. The intrathecal position of the catheters did not depend
      on the level of the lumbar puncture (P = 0.6246), but was dependent on the
      position of the patient during insertion of the catheter (P = 0.0093), and on the
      depth of insertion (P = 0.0099). Our study suggests that patients should be in a
      sitting position during insertion of a subarachnoid microcatheter and that the
      depth of insertion should not exceed 4 cm.

PMID- 8280543
TI  - Effect of late posture change on the level of spinal anaesthesia with plain
      bupivacaine.
AB  - We studied 40 patients, 18-60 yr, undergoing orthopaedic surgery of the lower
      limb under spinal anaesthesia. A midline lumbar puncture was performed in the L3
      4 interspace using a 27-gauge needle with the patient in the lateral horizontal
      position. Plain bupivacaine 3 ml at room temperature was injected. The cephalad
      level of analgesia was assessed by pinprick 60 min after injection of local
      anaesthetic, at the end of surgery and again after the patient was moved into
      bed. All patients had a segmental level of the block of L1-T5 at the beginning of
      the study. The upper half of the patient's body was then tilted to a 30 degrees
      head-up position. Segmental spread was subsequently assessed by pinprick at 5-min
      intervals for 30 min. In six of the 40 patients (15%), increased cephalad spread
      of spinal analgesia occurred. The mean time from induction of spinal anaesthesia
      was shorter in these six patients (mean 92 min, range 80-115 min) than in the
      patients whose block did not change or was decreasing during the 30-min test
      (mean 119 min, range 83-210 min) (P < 0.05). We conclude that the patient should
      remain in the supine horizontal position until recovery from the spinal block.

PMID- 8280544
TI  - Effect of extradural diamorphine on analgesia after caesarean section under
      subarachnoid block.
AB  - We have examined the efficacy, duration of action and side effects of extradural
      diamorphine alone and in combination with 1:200,000 adrenaline in a randomized,
      double-blind controlled study of 45 patients who underwent Caesarean section
      under spinal anaesthesia. Saline 10 ml, diamorphine 2.5 mg in saline 10 ml or
      diamorphine 2.5 mg in 1:200,000 adrenaline 10 ml were administered via the
      extradural route at delivery of the baby. Both diamorphine and diamorphine with
      adrenaline provided significantly prolonged analgesia compared with control (mean
      time to next analgesia (95% confidence interval) 17.3 h (12.0, 22.1 h), 15.9 h
      (10.6, 21.1 h), 5.7 h (1.5, 9.9 h), respectively) (P < 0.01). The addition of
      adrenaline increased the quality of analgesia 8 h after operation, but had no
      effect on the total amount of i.m. morphine administered during the first 24 h.
      The incidence of side effects was similar in all groups.

PMID- 8280545
TI  - Oral bromfenac 10 and 25 mg compared with sublingual buprenorphine 0.2 and 0.4 mg
      for postoperative pain relief.
AB  - The aim of this single-dose, randomized, positive control, double-dummy, double
      blind, parallel group study was to compare oral bromfenac 10 and 25 mg with
      sublingual buprenorphine 0.2 and 0.4 mg for treatment of postoperative pain. We
      studied 91 patients with moderate or severe pain after general surgical or
      orthopaedic operations, using pain intensity, pain relief, adverse effect, mood
      and sedation outcomes. There was a significant analgesic dose-response for
      buprenorphine, showing study sensitivity, but not for bromfenac. The two
      bromfenac treatments were significantly superior to the two buprenorphine
      treatments. Significantly more patients reported nausea with buprenorphine. There
      was evidence of a ceiling effect for analgesia with bromfenac.

PMID- 8280546
TI  - Patient-controlled analgesia with low dose background infusions after lower
      abdominal surgery in children.
AB  - Forty-five children (aged 6-12 yr) undergoing appendicectomy received one of
      three analgesic regimens using patient-controlled analgesia (PCA) with morphine:
      no background infusion (BO); background infusion 4 micrograms kg-1 h-1 (B4);
      background infusion 10 micrograms kg-1 h-1 (B10). Total consumption of morphine
      was greater in group B10 compared with groups B0 (P < 0.01) and B4 (P < 0.05).
      There was no significant difference in morphine consumption in groups B0 and B4.
      All three groups self-administered similar amounts of morphine and there were no
      significant differences in pain scores or incidence of excessive sedation. Group
      B4 suffered less hypoxaemia compared with groups B0 (P < 0.01) and B10 (P <
      0.001). Group B10 suffered more nausea and vomiting than groups B0 (P < 0.001)
      and B4 (P < 0.001), but there was no significant difference in the incidence of
      nausea and vomiting between groups B0 and B4. Groups B4 and B10 spent more time
      at night asleep than group B0 (P < 0.05). There were no significant differences
      between the groups in the amount of time spent asleep during the day. Inclusion
      of a background infusion of morphine 4 micrograms kg-1 h-1 in a PCA regimen for
      children did not increase the incidence of side effects and was associated with
      less hypoxaemia and a better sleep pattern than no background infusion.

PMID- 8280547
TI  - Pharmacokinetics of i.v. and rectal pethidine in children undergoing ophthalmic
      surgery.
AB  - We have studied the pharmacokinetics of i.v. and rectal pethidine in 20 children
      age 4-8 yr undergoing ophthalmic surgery. After i.v. administration, the
      clearance of pethidine was mean 10.4 (SD 1.7) ml kg-1 min-1, volume of
      distribution at steady state 2.8 (0.6) litre kg-1 and elimination half-life 3.0
      (0.5) h. After rectal administration, plasma pethidine concentrations varied
      greatly and peak concentrations appeared late, at 147 (44) min. The mean systemic
      bioavailability after rectal administration was approximately 55%. Because the
      bioavailability of rectal pethidine varies greatly, this route is not encouraged
      in the management of acute pain.

PMID- 8280548
TI  - Influence of Crohn's disease on the pharmacokinetics and pharmacodynamics of
      alfentanil.
AB  - We have compared the dose requirements, pharmacokinetics and pharmacodynamics of
      alfentanil in 12 patients with Crohn's disease and 10 control patients undergoing
      abdominal surgery. Plasma concentrations of alpha 1-acid glycoprotein (AAG) and
      alfentanil protein binding were also measured. Anaesthesia was induced with
      alfentanil 100 micrograms kg-1 and thiopentone, and maintained with nitrous oxide
      in oxygen and alfentanil 25-200 micrograms kg-1 h-1. Arterial blood samples were
      obtained before and after each change in the alfentanil infusion rate and for 6 h
      after stopping the infusion. Pharmacokinetic data were derived using non
      compartmental methods. Alfentanil concentration-effect data were evaluated by non
      linear regression, where effect was either response or no response to surgical
      stimulation. Mean intraoperative alfentanil requirement was greater in patients
      with Crohn's disease (2.48 micrograms kg-1 min-1) than in control patients (1.35
      micrograms kg-1 min-1) (P < 0.01). Mean elimination half-life, total plasma
      clearance and steady state distribution volume in patients with Crohn's disease
      were comparable to those in control patients (80 vs 81 min, 5.7 vs 6.4 ml kg-1
      min-1 and 0.70 vs 0.68 litre kg-1, respectively). Mean plasma concentration at
      which the probability of no response was 50% for the intra-abdominal period of
      surgery was greater in the Crohn group (359 ng ml-1) than in the control group
      (199 ng ml-1) (P < 0.02). Plasma AAG concentrations were greater in the Crohn
      group, but the free fraction of alfentanil was similar in both groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8280549
TI  - Electroacupuncture in anaesthesia for hysterectomy.
AB  - We have studied the effects of electroacupuncture at classical acupuncture
      points, applied before and during surgery in patients undergoing hysterectomy, on
      postoperative pain and metabolic stress responses in a prospective, randomized
      and patient-blinded manner. Fifty otherwise healthy women were allocated randomly
      to receive or not receive electroacupuncture. Electroacupuncture was begun 20 min
      before skin incision and continued to the end of surgery. All patients received
      similar general anaesthesia and all received patient-controlled analgesia (PCA)
      after operation. Postoperative pain in the two groups was evaluated by recording
      analgesic requirements by PCA and by pain-rating performed by patients and
      nursing staff. There were no significant differences between the two groups in
      postoperative analgesic requirements, pain-rating or metabolic stress responses.

PMID- 8280550
TI  - Effects of small concentrations of isoflurane on some psychometric measurements.
AB  - We have investigated the effects of 9.5% and 14.1% MAC concentrations of
      isoflurane on some psychometric measurements. Both concentrations depressed peak
      saccadic velocity (P < 0.01), choice reaction time (P < 0.05) and visual analogue
      scores for sedation (P < 0.05), but not the critical flicker fusion threshold.
      The incidence of errors in saccade tasks increased in a dose-related fashion,
      which made analysis of peak saccadic velocity less accurate at more than 10% MAC.
      The percentage error itself was an indicator of the depth of sedation. All the
      objective measures correlated highly with the estimated brain tension of
      isoflurane (r2 = 0.86-0.96), but not the visual analogue score for sedation (r2 =
      0.51). This suggests that a combination of peak saccadic velocity, percentage
      error and choice reaction time is a potentially useful batch of tests to measure
      recovery from anaesthesia.

PMID- 8280551
TI  - Antiemetic efficacy of prophylactic ondansetron in laparoscopic surgery:
      randomized, double-blind comparison with metoclopramide.
AB  - In a randomized, double-blind study, we have compared the prophylactic antiemetic
      efficacy of ondansetron with that of metoclopramide in 123 patients undergoing
      general anaesthesia for day-case gynaecological laparoscopic surgery. The
      patients received either i.v. ondansetron 4 mg or metoclopramide 10 mg
      immediately before a standard anaesthetic. The number of patients with no nausea
      or vomiting in the ondansteron group was 50 (82%) compared with 29 (47%) in the
      metoclopramide group (P < 0.001). In those patients with a previous history of
      postoperative nausea and vomiting, nausea was less severe in those receiving
      ondansetron compared with those receiving metoclopramide (P < 0.05). We conclude
      that preoperative prophylactic administration of i.v. ondansetron was superior to
      metoclopramide in preventing nausea and vomiting after general anaesthesia for
      day-case gynaecological laparoscopic surgery.

PMID- 8280552
TI  - Effect of thiopentone on motor evoked potentials induced by transcranial magnetic
      stimulation in humans.
AB  - We have studied the effect of repeated doses of thiopentone on motor evoked
      potentials (MEP) after transcranial magnetic stimulation in 13 patients.
      Thiopentone was administered i.v. in an initial dose of 2 mg kg-1, followed by
      repeated doses (1 mg kg-1 every 3 min) until the appearance of burst suppression
      on the EEG. The total dose administered was mean 10.7 (SD 2.6) mg kg-1. The
      magnetic coil was placed over the MEP scalp stimulation region and evoked
      electromyographic responses were recorded from the contralateral abductor
      pollicis brevis. After an initial dose of thiopentone, reproducible MEP responses
      were recorded in all patients, but amplitudes were reduced to 42.8% of baseline
      values. Further administration of repeated doses of thiopentone produced a dose
      dependent decrease in success rate of MEP recordings and a significant reduction
      in MEP amplitude (P < 0.01). Latency did not change significantly, although there
      was a tendency to increase. During burst suppression on the EEG, MEP was not
      recorded successfully in all patients. We conclude that MEP recording during the
      administration of thiopentone is feasible only at a minimum dose, with a marked
      reduction in MEP amplitude.

PMID- 8280553
TI  - Blood loss during repair of craniosynostosis.
AB  - Surgical repair of craniosynostosis carries a high risk with large blood losses.
      Over a 2-yr period, we have managed 115 patients undergoing craniosynostosis
      repair with peroperative haemodilution to achieve a final PCV of 0.28-0.35.
      Measurements of PCV allowed calculation of estimated blood losses and transfused
      volumes in terms of red blood cell mass. Total estimated red cell volume lost was
      91 +/- 66% of patient's estimated red blood cell volume during the peroperative
      period. The type of skull deformation and surgical procedure determined the
      extent of peroperative bleeding. Peroperative transfusion was satisfactory in 48%
      of patients and slight overtransfusion was noted in 32%. During the postoperative
      period, liberal administration of blood led to overtransfusion and possibly
      unnecessary transfusion in 74% of patients. Because of the well known risks of
      transmission of infectious disease, strict volume compensation with development
      of haemodilution and autotransfusion procedures should be used to limit these
      risks.

PMID- 8280554
TI  - Postoperative multiple organ dysfunction syndrome associated with gut mucosal
      hypoperfusion, increased neutrophil degranulation and C1-esterase inhibitor
      depletion.
AB  - We have examined the relationship between gut mucosal perfusion, as determined by
      gastric intramucosal pH (pHi), changes in plasma neutrophil elastase
      concentrations and components of the contact system during elective major surgery
      and related these findings to patient outcome. Of the 26 patients studied, 16
      developed gut mucosal hypoperfusion (pHi < 7.32) by the end of surgery; four of
      these developed multiple organ dysfunction syndrome; three of these died. In this
      group there was a significant increase in neutrophil elastase (P < 0.005) and
      significant reductions in plasma components of the contact system from
      immediately before surgery to 24 h later. Ten patients maintained gut mucosal
      perfusion (pHi > or = 7.32); none of these developed life threatening
      complications. In this group there was no significant increase in neutrophil
      elastase and, although there were significant reductions in some plasma
      components of the contact system, concentrations of C1-esterase inhibitor (the
      main inhibitor of the contact system) were not significantly reduced. We conclude
      that gut mucosal hypoperfusion, neutrophil degranulation and activation of the
      contact system to the extent that C1-esterase inhibitor becomes depleted are
      associated with a poor outcome after major surgery.

PMID- 8280555
TI  - Lung management during cardiopulmonary bypass: is continuous positive airways
      pressure beneficial?
AB  - It is not clear if the use of continuous positive airway pressure (CPAP) during
      cardiopulmonary bypass (CPB) improves lung function after cardiac surgery. We
      have measured alveolar-arterial oxygen partial pressure difference (PAO2-PaO2) in
      61 patients undergoing elective coronary artery bypass surgery. We studied three
      groups of patients: in group 1 the lungs were disconnected from the breathing
      system (no CPAP) during CPB; in group 2, 5 cm H2O CPAP with air was applied to
      the lungs; in group 3, 5 cm H2O of CPAP was applied with 100% oxygen. (PAO2-PaO2)
      was measured before CPB and then at 30 min, 4 h and 8 h after CPB. Compared with
      group 1 (no CPAP), (PAO2-PaO2) was significantly smaller in groups 2 and 3 at 30
      min (P = 0.036), but not at 4 h and 8 h after CPB (P = 0.32, P = 0.96). The time
      to extubation (P = 0.42) and early extubation (P = 0.87) were not affected by the
      use of CPAP. The results of this study do not support the use of CPAP during CPB
      as a mechanism of improving lung function after cardiac surgery.

PMID- 8280556
TI  - Comparison of the haemodynamic effects of enoximone and piroximone in patients
      after cardiac surgery.
AB  - We have compared the haemodynamic effects of the imidazole derivative
      phosphodiesterase inhibitors enoximone and piroximone in patients with low
      cardiac output after cardiac surgery. Ten patients (group E) received enoximone
      and 10 patients (group P) received piroximone, both at a loading dose of 0.5 mg
      kg-1 followed by an infusion of 5 micrograms kg-1 min-1. In both groups the main
      changes with time were increases in cardiac index (maximum 24.5% in group E,
      25.8% in group P) and decreases in systemic vascular resistance (maximum 26.8% in
      group E and 24.8% in group P). There were moderate increases in heart rate
      (maximum 11.3% in group E and 13% in group P) but a greater percentage decrease
      in mean arterial pressure in group E (maximum 11.9% vs 7.9%) with time. One
      patient in group E developed hypertension during the loading dose. Two patients
      in group E and two in group P developed hypotension during the loading dose. One
      patient in group E developed ventricular extrasystoles which may have been
      related to the drug being studied.

PMID- 8280557
TI  - Isoflurane inhibits insulin secretion from isolated rat pancreatic islets of
      Langerhans.
AB  - We have investigated the effects of isoflurane on insulin secretion in vitro from
      rat isolated islets of Langerhans and found a significant, dose-related and
      reversible inhibition of insulin secretion. Isoflurane 2% decreased insulin
      secretion stimulated by glucose 20 mmol litre-1 to basal, nonstimulated values.
      In other studies to identify the stage in the stimulus secretion pathway for
      insulin at which the anaesthetic may exert an inhibitory action, we have
      stimulated insulin release using glyceraldehyde and a phorbol ester. Insulin
      secretion induced by these secretagogues was also blocked by isoflurane. This
      suggests that the inhibitory effect of the anaesthetic agent may be at a site
      distal to stimulation of insulin secretion by glyceraldehyde and phorbol esters.

PMID- 8280558
TI  - Effects of fentanyl on the rat aorta are mediated by alpha-adrenoceptors rather
      than by the endothelium.
AB  - We have assessed if fentanyl interacts with the endothelium to affect vessel
      tone. In the presence or absence of endothelium, fentanyl in concentrations
      greater than 10(-7) mol litre-1 decreased the sensitivity of the rat aortic rings
      to phenylephrine, but fentanyl in smaller concentrations had no significant
      effect. Rings, with or without endothelium, and pre-contracted by phenylephrine
      were relaxed by fentanyl, and this relaxation was not inhibited by the opioid
      receptor antagonist, naloxone. Pretreatment of the rings with either fentanyl or
      phentolamine protected alpha-adrenoceptors from block by the alpha-adrenoceptor
      antagonist, phenoxybenzamine. We conclude that, in the rat aorta, fentanyl
      induced relaxation was mediated by alpha-adrenergic receptors, and that the
      endothelium modulated, but did not mediate, this relaxation.

PMID- 8280559
TI  - Improvement of brain electrical activity during treatment of porcine malignant
      hyperthermia with dantrolene.
AB  - Three months before this study, susceptibility for malignant hyperthermia (MH)
      had been tested in 15 pigs. In all pigs, MH was triggered by administration of 1%
      halothane. Brain electrical activity was examined during therapy of MH with and
      without administration of dantrolene. From the EEG, power densities in selected
      frequencies and the median frequency of the power spectrum were calculated.
      Therapy was started when severe respiratory changes were observed (PaCO2 > 10
      kPa, mixed venous oxygen tension (PvO2) < 4 kPa). At this time, heart rate
      exceeded 150 beat min-1, mean arterial pressure (MAP) was less than 60 mm Hg and
      median frequency was less than 2 Hz. EEG was isoelectric (n = 6) or showed slow
      polymorphic delta-activity. For therapy, administration of all anaesthetics was
      terminated, 100% oxygen was delivered and ventilation was increased four-fold.
      Acidosis was treated by administration of sodium bicarbonate 2-4 mmol litre-1 kg
      1. Animals were allocated randomly to one of two groups: group I (control, n = 7)
      received no dantrolene; group II (n = 8) received dantrolene 2.5 mg kg-1 i.v. All
      variables were measured over a period of 60 min after therapy: EEG, HR and MAP
      were recorded continuously and blood-gas tensions, arterial potassium and glucose
      concentrations and pH were measured every 150 s. In group I (no dantrolene)
      minor, transient improvements in EEG activity were noted, but all animals died
      within 15-25 min after the start of therapy. In dantrolene-treated animals, EEG
      total power and median frequency increased within 5 min.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8280560
TI  - Anaesthesia of animals for biomedical research.

PMID- 8280561
TI  - Comparison of propofol with enflurane during hypotensive anaesthesia for middle
      ear surgery.
AB  - Forty patients undergoing middle ear surgery were allocated randomly to receive
      propofol induction and maintenance, or thiopentone induction and enflurane
      maintenance for anaesthesia. Both groups also received fentanyl, alcuronium,
      nitrous oxide and oxygen. If this did not reduce systolic arterial pressure to 70
      mm Hg, labetalol, glyceryl trinitrate (GTN), or both, was administered. Fifteen
      control patients had enflurane anaesthesia without hypotension. Pre- and
      postoperative psychometric tests were performed in all groups. The propofol group
      received significantly more labetalol (P = 0.014) and GTN (P = 0.004) than the
      enflurane group. There was a greater increase in reaction times after operation
      in the study groups (P < 0.05) compared with controls. There was no difference
      between the propofol and enflurane groups in control of arterial pressure,
      recovery from anaesthesia or psychometric testing.

PMID- 8280562
TI  - Complications of tracheotomy.
AB  - A patient underwent elective tracheotomy before resection of the floor of the
      mouth. After operation, several life-threatening complications arose from this
      tracheotomy, including surgical emphysema of the tracheal mucosa which has not
      been described previously.

PMID- 8280563
TI  - Compartment syndrome after use of an automatic arterial pressure monitoring
      device.
AB  - A case of compartment syndrome is reported as a rare complication of the use of a
      continuous arterial pressure monitoring device. For surgical procedures of very
      long duration, the way in which these monitoring devices are used may need to be
      modified, or alternative forms of pressure monitoring used.

PMID- 8280564
TI  - Plasma drug concentrations: description and interpretation of the biexponential
      decay.
AB  - Information about the time course of the plasma concentrations of a drug after
      its i.v. bolus injection is necessary for understanding the time course of the
      effect of the drug. If an investigator has established that the time course of
      the plasma concentrations conforms to a biexponential function, understanding the
      data is facilitated by description of the time course which simply summarizes the
      data in a quantitative fashion and interpretation of the findings based on
      certain assumptions. Interpretation may be based on the assumption of
      compartments, or on a "whole body" approach. The experimentally obtained plasma
      concentrations of a drug may be described quantitatively by an equation and, if
      the "whole body" interpretation is selected in preference tot he compartmental
      interpretation, the four parameters are: the initial and the terminal volumes of
      distribution (Vc and Vterm) and the rate constants for the loss from Vc and for
      the dilution within the whole body (k(loss) and k(mix), respectively).

PMID- 8280565
TI  - Prediction of arterial PCO2 from end-tidal PCO2.

PMID- 8280566
TI  - Suxamethonium in day-case anaesthesia.

PMID- 8280567
TI  - Correlation of child's age with infusion rates of mivacurium.

PMID- 8280568
TI  - Fentanyl and the extradural sieve.

PMID- 8280569
TI  - Ivox, oxygen balance and the heart.

PMID- 8280570
TI  - Venous air embolism with a water jet dissector.

PMID- 8280571
TI  - Spin label techniques for the detection of malignant hyperthermia.

PMID- 8280572
TI  - Defining right lower quadrant pain in the AIDS patient.

PMID- 8280573
TI  - Dollar costs of prostatectomy and TURP.

PMID- 8280574
TI  - Ovarian cancer risk counseling: a guide for the practitioner.
AB  - Epithelial ovarian cancer is the most common gynecologic cancer diagnosed in
      women in the United States, with over 20,000 newly diagnosed cases per year. Over
      70% of these patients present with advanced, stage III or IV disease, resulting
      in more than 13,000 deaths each year. This figure is all the more tragic given
      the long-term disease-free survival of approximately 85% for early stage disease.
      The natural history of the disease is poorly understood but is characterized by
      an insidious onset with vague, non-specific symptoms (which are commonly
      overlooked), and a high but often transient response to current surgical and
      chemotherapeutic approaches. It is commonly associated with a prolonged and
      painful death accompanied by repeat bowel obstructions, malnutrition, and
      immunologic compromise. In addition to the pain and suffering and loss of life of
      those affected with the disease, there is a profound and long-lasting impact on
      the entire family who experience the loss.

PMID- 8280576
TI  - Newly identified estrogen source may give clues to breast tumor development.

PMID- 8280575
TI  - Abnormalities in chest X-rays in children with AIDS and PCP.

PMID- 8280577
TI  - Current status of operative laparoscopy in gynecologic oncology.
AB  - The role of laparoscopy in gynecologic oncology has expanded in the last few
      years to include a variety of situations and cancers. Patients with invasive
      cervical carcinoma can be spared radical hysterectomy if laparoscopy documents
      positive lymph nodes. Therapeutic laparoscopic pelvic lymphadenectomy has been
      performed successfully in patients with small cervical lesions. Laparoscopy can
      be used for staging in patients with advanced cervical cancer who are scheduled
      for definitive radiotherapy. Laparoscopically assisted surgical staging is also
      feasible, safe, and adequate in patients with clinical stage I endometrial
      cancer, and is being investigated in patients with stage I ovarian cancer. Second
      look laparoscopy is proving useful in ovarian cancer patients who are candidates
      for a second-look procedure. Laparoscopic pelvic lymphadenectomy is being
      investigated in patients with small stage I vaginal carcinoma who are being
      considered for treatment with brachytherapy alone.

PMID- 8280578
TI  - Clinical trials referral resource. Extensive-stage small-cell lung cancer.

PMID- 8280579
TI  - Management of gestational trophoblastic disease.
AB  - Gestational trophoblastic disease (GTD) embraces a spectrum of neoplasms of the
      placenta. Hydatidiform moles are managed by molar evacuation and expectant
      surveillance of quantitative serum hCG levels. Approximately 80% of complete
      moles and more than 90% to 95% of partial moles will enter complete remission
      without further therapy. Malignant GTD can occur after any type of pregnancy. The
      prognosis is determined by several clinical risk factors, including anatomic
      site(s) of disease, duration of disease, hCG level, and type of antecedent
      pregnancy. Patients with nonmetastatic and low-risk metastatic GTD have an
      excellent outcome when treated with single-agent chemotherapy. Even patients with
      high-risk disease may have survival rates of approximately 80%, but only if
      patients in this category are treated with initial aggressive multiagent
      chemotherapy. Combined modality therapy is often required to optimize outcome in
      high-risk patients. Most women with malignant GTD can be cured and retain
      reproductive function.

PMID- 8280580
TI  - Future directions in 3-dimensional radiation treatment planning.
AB  - In recent years, computed tomography data have been used to build three
      dimensional (3D) patient models for radiation treatment planning. The strength of
      3D treatment planning systems lies in their ability to substantially improve the
      precision of radiation therapy and provide some of the tools needed to improve
      dose conformation. This article describes the V2 virtual simulation system used
      at the University of North Carolina at Chapel Hill. The virtual simulator allows
      the patient model to be rotated to determine the best beam angles and calculates
      the positions of the table, gantry, and collimator necessary to achieve desired
      beam orientations. Considerable disagreement remains as to how to produce an
      optimal radiation treatment plan using 3D systems. The University of North
      Carolina's VISTAnet project provides real-time 3D radiation dose calculation and
      display, allowing the user to search for the optimal plan.

PMID- 8280581
TI  - Global programme on AIDS.

PMID- 8280583
TI  - Diarrhoeal Disease Control (CDD) Programme.

PMID- 8280582
TI  - Expanded programme on immunization (EPI).

PMID- 8280584
TI  - Prisoners in France are to be treated in general hospitals.

PMID- 8280585
TI  - An agenda for change.

PMID- 8280586
TI  - Europe: the challenge of the treaty.

PMID- 8280587
TI  - Small cell lung cancer (continuing education credit).

PMID- 8280588
TI  - Community placement: auditing the quality.
AB  - The second article in this two-part series analyses the development of an
      educational audit tool to examine the quality of the learning environment for
      student nurses undergoing community placement. Deficits in existing tools are
      identified and rationales suggested to overcome perceived problems. The article
      also discusses the issues which emerged during the piloting of the tool and its
      value as an audit instrument.

PMID- 8280590
TI  - The Clay interview. Yvonne Moores: a unique nurse. Interview by Trevor Clay.

PMID- 8280589
TI  - Diabetes education in Grampian: a study.
AB  - In a widely scattered area such as Grampian, patients' needs, staffing
      requirements and methods of delivery of health care are different from those
      found in a densely populated urban area. Although this may be seen as desirable
      from the point of view of meeting the individual needs of patients from diverse
      backgrounds, there are also problems in that consistency of quality of care may
      fluctuate. Recognising that the quantity and quality of patient education offered
      to diabetic patients in Grampian may vary according to their geographical
      location, the author and her colleagues set out to investigate the provision and
      quality of education on diabetes for both patients and nurses. The results
      indicated that there were significant gaps in patients', relatives' and nurses'
      knowledge of diabetes. Introducing a standard diabetes education system was found
      to be one way of improving levels of knowledge in the Grampian area.

PMID- 8280591
TI  - Community care. Community? What community is that?

PMID- 8280592
TI  - Disneycare.

PMID- 8280593
TI  - Health promotion: slimline tonic.

PMID- 8280595
TI  - One minute wisdom. Named doctoring should be made mandatory.

PMID- 8280594
TI  - Workwise. Nursing's rites and wrongs of passage.

PMID- 8280596
TI  - Dame Margot Turner. Distinguished survivor.

PMID- 8280597
TI  - The role of DNA topoisomerases II in drug resistance.
AB  - The essential nuclear enzyme DNA topoisomerase II is required for the action of a
      significant number of cytotoxic compounds. Resistance mechanisms identified in
      cell lines include down-regulation of protein expression, by gene methylation or
      down-regulation of mRNA, altered drug-DNA-protein interaction or ATP binding,
      post translational modification of the protein and alteration in expression of
      the isoenzymes. There is a lack of data relating the findings from these cell
      lines to observations from clinical practice and the evolution of specific drug
      resistance in patients. For leukaemias, several studies using different in vitro
      chemosensitivity assays show a correlation between the clinical response and the
      in vitro sensitivity (Sargent & Taylor, 1989; Pieters et al, 1989; Larsson et al,
      1992; Bosanquet, 1991). From this data, outcome may be related to the mechanism
      of resistance and allow the development of strategies to overcome them. This
      includes the use of colony stimulating factors or antimetabolites or the
      development of new drugs to utilize topoisomerases as their target but which are
      not transported by P-glycoprotein. Thus an understanding of these mechanisms may
      help in the optimal use of the topoisomerase II inhibitors.

PMID- 8280598
TI  - Pure red cell aplasia in childhood and adolescence: pathogenesis and approaches
      to diagnosis.

PMID- 8280599
TI  - Growth factor-induced process formation of megakaryocytes derived from CFU-MK.
AB  - The extended cytoplasmic processes from megakaryocytes (MK) are believed to be
      structural intermediates between MK and platelets. We could observe
      differentiation of purified rat CFU-MK toward mature MK to form extended
      cytoplasmic processes. Recombinant rat interleukin-3 (IL-3), human erythropoietin
      (Epo), and human interleukin-6 (IL-6) each was able to stimulate process
      formation although they varied somewhat in their potential. Electron microscopic
      observations showed that these processes were very similar to those from mature
      MK so far reported. The combination of IL-6 with IL-3 or Epo synergistically
      increased the number of MK forming processes without further increase in the
      number of total MK formed in the presence of IL-3 or Epo alone. In addition, IL-6
      significantly increased the megakaryocytic diameter and DNA content of MK induced
      by IL-3 or Epo and shortened the MK transit time to hasten the process formation
      of MK. These findings suggest that IL-6 promotes further maturity in both the
      cytoplasm and ploidy of MK to form extended cytoplasmic processes. The ability of
      these factors to generate the process formation in vitro may be related to their
      thrombopoietic effects in vivo.

PMID- 8280600
TI  - Cultured human NK cells express the Ki-1/CD30 antigen.
AB  - In this study we show that in vitro cultured human polyclonal NK cell lines and
      clones express the Ki-1/CD30 Hodgkin-associated antigen, identified by the BER-H2
      monoclonal antibody. The percentage of BER-H2+ cells ranged from 19% to 67% in
      five polyclonal NK cell lines and was 31% and 20% in two NK clones. The intensity
      of BER-H2 mAb staining on cultured NK cells was remarkably lower than that found
      on the L540 Hodgkin's lymphoma cell line. Resting PBL populations that had been
      enriched for NK cells failed to react with the BER-H2 mAb. Western blot analysis
      performed on cell lysates from a polyclonal NK cell line and from the NK3.3 NK
      like cell line revealed that BER-H2-reactive molecules consisted of two major
      bands of approximately 110 kD and 100 kD. Two bands displaying an identical
      electrophoretic mobility were also found in lysates of the L540 cell line. The
      BER-H2 mAb failed to inhibit the nonspecific activated killer activity of
      cultured NK cells against both K562 and MeWo tumour target cells. In addition,
      the BER-H2 mAb was unable to trigger the cytolytic activity of NK cells in a
      redirected killing assay. The observation that cultured human NK cells express
      the Ki-1/CD30 antigen may be of relevance for the possible lineage assignment of
      K11/CD30+ lymphoid cell neoplasia with unrearranged TCR genes.

PMID- 8280601
TI  - Detection of clonal platelet antibodies in immunologically-mediated
      thrombocytopenias: association with circulating clonal/oligoclonal B cells.
AB  - Aware that T and B cells in autoimmune thrombocytopenia are abnormal, including
      the existence of clonal B cell populations, we sought to characterize this clonal
      phenomenon in various immunological thrombocytopenias using platelet antibody
      light chain analysis, flow cytometry, Southern blot analysis, and PCR. Using a
      monoclonal antibody-antigen capture ELISA, we analysed sera from 21 of 26
      patients with autoimmune, alloimmune, or drug-induced immunological
      thrombocytopenia for the light chain phenotypes of their platelet antibodies.
      Alloantibodies and drug-dependent antibodies from four and 14 patients,
      respectively, were found that expressed a predominant type of light chain,
      suggesting that these platelet-reactive antibodies were monoclonal or oligoclonal
      in nature. 14 of the 26 patients were available for light chain B cell
      phenotyping studies. Of these 14 patients, thrombocytopenia was due to
      autoimmunity in two, drug-induced immunity in four, and alloimmunity in eight. We
      detected clonal populations of B cells in all 14 patients by flow cytometry.
      Although six of these latter patients possessed platelet antibodies with clonal
      characteristics, light chain phenotypes of antibodies in five patients were
      opposite to those of their B cells. Eight of these patients were further examined
      for immunoglobulin gene rearrangement using Southern and/or polymerase chain
      reaction analysis. In all eight patients we detected clonal or oligoclonal B cell
      populations. Only two of these patients had malignancies (chronic lymphocytic
      leukaemia) that would be expected to have detectable clonal B cells, and thus the
      mechanism for clonal expansion in the other six patients did not appear to be
      related to an obvious neoplastic process. Prior to these studies, detection of
      clonal B cells in thrombocytopenic patients without known malignancies was
      limited to individuals with autoimmune thrombocytopenia, prompting the
      speculation that this particular autoimmune disorder arises from B cell
      dysregulation, rather than from expansion of specific autoantibody producing B
      cell clones. In contrast, the current studies provide evidence that clonal B
      cells are common to patients with any form of immunologically-mediated
      thrombocytopenia. Moreover, the majority of the platelet antibodies (86%) present
      in these disorders exhibited monoclonal characteristics in that there was an
      apparent restriction in light chain usage.

PMID- 8280602
TI  - Evaluating survival after allogeneic bone marrow transplant for chronic myeloid
      leukaemia in chronic phase: a comparison of transplant versus no-transplant in a
      cohort of 258 patients first seen in Italy between 1984 and 1986. Italian
      Cooperative Study Group on Chronic Myeloid Leukaemia.
AB  - Information on the outcome of allogeneic bone marrow transplant (BMT) for chronic
      myeloid leukaemia (CML) was previously provided by BMT centres or registries.
      This report uses the data from another source, based on a cohort of 258 patients
      aged 50 or less who were first seen and recruited between 1984 and 1986 at 55
      Italian hospitals. These patients were registered and followed for a prospective
      study of the course and prognosis of CML, without any obligations for treatment.
      All patients had Ph+ CML; 50 of them were transplanted in first chronic phase
      (CP), and 208 were not transplanted. Leukaemia-free survival at 8 years was 34%
      (95% CI 20-47%) for the transplant group versus zero in the non-transplant group.
      Overall survival at 8 years was 43% (95% CI 29-57%) for the transplant group
      versus 25% (95% CI 19-32%) in the non-transplant group (P = 0.24). The difference
      in overall survival between transplant and non-transplant was significant in
      patients less than 30 years old (P = 0.035), but not in patients aged 30-50 years
      (P = 0.439). This report points out that although freedom from leukaemia could be
      obtained only with BMT, a beneficial effect of BMT on overall survival could be
      detected only in a patients' subset, and that many hundreds of cases and a decade
      could be necessary to evaluate the effect on survival of new transplant policies.

PMID- 8280603
TI  - Prognostic factors in elderly patients with acute myeloid leukaemia: development
      of a model to predict survival.
AB  - With an increasing number of elderly patients presenting with acute myeloid
      leukaemia and with recent reports of worthwhile remission rates and survival
      times following treatment with intensive chemotherapy, there is a pressing need
      to identify criteria to assist in the selection of appropriate therapy for
      elderly patients. We have performed multivariate Cox proportional hazard
      regression analysis of data prospectively collected during the treatment of 104
      patients aged 60 and over treated in a multi-centre study with a standardized
      regimen of mitozantrone and cytosine arabinoside for induction and consolidation.
      Four readily available parameters, namely urea, performance status, peripheral
      blood blast count and presence of hepatomegaly, were identified from which a
      prognostic model to predict survival has been developed. The model was found to
      be accurate in predicting survival in the cohort of patients from which it was
      developed, but needs to be validated in a further test population studied
      prospectively. Its simplicity suggests that it may be particularly useful in the
      selection of elderly patients with AML most likely to benefit from intensive
      chemotherapy.

PMID- 8280604
TI  - Monitoring of relapse and remission in acute leukaemias by DNA-fingerprint
      analysis.
AB  - DNA-fingerprint (DNA-F) analysis was successfully performed with DNA from 22
      adult patients with acute leukaemia, including 13 patients with acute myeloid
      leukaemia (AML) and nine patients with acute lymphoblastic leukaemia (ALL). The
      purpose of this study was to detect differences between the leukaemic phase (at
      diagnosis or relapse) and remission-phase DNA. We applied one simple repeat probe
      (GTG)5 and one minisatellite (M13) after DNA-digestion with different restriction
      endonucleases (HinfI and HaeIII) and agarose gel electrophoresis. In 7/13
      patients with AML and 5/9 patients with ALL it was possible to detect loss of
      bands, additional bands or band shift with at least one of the probes. Together
      the probes M13 and (GTG)5 unveiled deviating fingerprint patterns in 54.6% of
      patients between leukaemic cells and remission-phase leucocytes. Allogeneic bone
      marrow transplantation was performed on six patients. In each case the DNA-F
      pattern of the donor was different from the relapse and the remission-phase
      pattern. We conclude from our studies that the probes M13 and (GTG)5 are useful
      in the detection of relapse and remission in acute leukaemias after chemotherapy
      and bone marrow transplantation.

PMID- 8280605
TI  - Leukaemia arising in donor cells following allogeneic bone marrow transplantation
      for beta thalassaemia demonstrated by immunological, DNA and molecular
      cytogenetic analysis.
AB  - Combined DNA analysis, molecular cytogenetic and immunological techniques have
      been used to identify the donor origin of common acute lymphoblastic leukaemia
      (cALL) which arose in a male patient with beta thalassaemia major, 5 years after
      an allogeneic bone marrow transplant from his HLA-matched sister. The necessity
      of using multiple techniques in this and similar cases is emphasized and the
      possible mechanisms for the development of donor leukaemia and the leukaemic
      transformation of donor cells are discussed.

PMID- 8280606
TI  - Anti-fibrinogen antibody mediates fibrinogen binding to platelet membrane
      glycoprotein IIb-IIIa.
AB  - The binding of fibrinogen to platelets requires the agonist activation of
      platelet membrane glycoprotein IIb/IIIa. We have now found an anti-fibrinogen
      polyclonal antibody (YCU-R3) that increases the fibrinogen affinity of GPIIb/IIIa
      binding function (activation) and subsequent platelet aggregation. The addition
      of intact IgG, F(ab)2 fragments or Fab fragments induced platelet aggregation.
      The antibody-mediated fibrinogen binding was specific and saturable. This binding
      was inhibited by native fibrinogen, the RGDS peptide, the peptide of the C
      terminus gamma chain of fibrinogen (gamma 397-411), and the anti-GPIIb/IIIa
      monoclonal antibody (LJ-CP8). The antibody-dependent fibrinogen binding was
      similar to that induced by ADP. Moreover, after pretreatment with the anti
      fibrinogen antibody and fibrinogen, formalin-fixed platelets bound to fibrinogen
      saturably. These results suggest that this anti-fibrinogen antibody may function
      as partial agonist.

PMID- 8280607
TI  - The inter-relationship of factor VII and its activity state with plasma lipids in
      healthy male adults.
AB  - A close inter-relationship between raised factor VII clotting activity and
      elevated blood lipids, particularly serum triglycerides, is well established. A
      study of factor VII, its activation state and of plasma lipids has been
      undertaken in two groups of healthy middle-aged males to elucidate this
      mechanism. A control group with normal factor VII levels were closely matched for
      age and body-mass index with a second group with elevated levels. Factor VII
      assays, using rabbit and bovine thromboplastin and a factor VII Ag method, were
      employed. Triglycerides correlated with the rabbit factor VII thromboplastin
      assay and factor VII Ag (P < 0.05) but not with the bovine thromboplastin method.
      Higher HDL-cholesterol and apolipoprotein A-I levels were found in subjects with
      increased factor VII (P < 0.001) and appeared to be due to differences in alcohol
      consumption. Cholesterol levels were significantly higher with elevated factor
      VII. Differential testing suggests that higher factor VII is predominantly
      mediated through a rise in total VII, rather than an increase in its activity
      state.

PMID- 8280608
TI  - Haemoglobin Manukau beta 67[E11] Val-->Gly: transfusion-dependent haemolytic
      anaemia ameliorated by coexisting alpha thalassaemia.
AB  - Haemoglobin Manukau (beta 67 Val-->Gly) is a novel haemoglobin variant presenting
      in two brothers as nonspherocytic haemolytic anaemia which became transfusion
      dependent by 6 months of age. The severity of clinical expression seems to be
      modulated by coexisting alpha thalassaemia: the severely affected children have a
      normal complement of alpha globin genes with an unusual genotype (-alpha
      3.7/alpha alpha alpha 3-7), while their father, who carries the abnormal gene
      with minimal symptoms, has homozygous alpha+ thalassaemia (-alpha 3.7/-alpha
      3.7). Another unusual feature of this case is the association of the beta 67 Val-
      >Gly mutation with modification of beta 141 Leu to a residue (believed to be
      hydroxyleucine) that is not detected by standard amino acid analysis. This
      finding offers an explanation for the previous report of an association of
      another mutation at this site (Hb Sydney beta 67 Val-->Ala) with Hb Coventry
      (deletion of beta 141 Leu).

PMID- 8280609
TI  - Megakaryocyte colony stimulating activity in allogenic bone marrow recipients
      prepared with busulfan and cyclophosphamide.
AB  - Increased megakaryocyte colony stimulating activity (MK-CSA) has been reported
      after total body irradiation (TBI) for bone marrow transplant (BMT). We studied
      the effect of a busulfan (Bu) and cyclophosphamide (Cy) marrow transplant
      conditioning regimen, without radiation, on MK-CSA production. Initial screening
      of MK-CSA was done on previously collected and banked sera from 14 BMT patients.
      MK-CSA was expressed as the ability to stimulate growth of megakaryocyte
      progenitors (CFU-MK) in standard plasma clot cultures. In the initial samples, MK
      CSA peaked at day 7. This preliminary data led to a prospective study of MK-CSA
      and clinical parameters in seven allogeneic recipients. MK-CSA activity increased
      from day -7 pre-transplant (2.9 +/- 1.7 CFU-MK/10(5) NATD, mean +/- SD) to day 0
      (10.3 +/- 4.7 CFU-MK) and peaked by day 9 post-transplant (20.6 +/- 6.4 CFU-MK).
      MK-CSA activity decreased in all seven patients by day 21 at which time five of
      seven patients studied had recovery of platelet counts to greater than 100 x
      10(9)/l. MK-CSA activity rose rapidly in both groups of sera after the initiation
      of this non-irradiation, BMT preparative regimen. High MK-CSA levels, early after
      transplant, may contribute to the rapid platelet recovery in some patients.

PMID- 8280610
TI  - Relapse of aplastic anaemia after immunosuppressive treatment: a report from the
      European Bone Marrow Transplantation Group SAA Working Party.
AB  - This study was designed to determine the incidence of relapse and factors
      predictive for relapse in 719 patients with severe aplastic anaemia (SAA) after
      immunosuppressive treatment (IS). Patients developing myelodysplasia or acute
      leukaemia after IS, and patients receiving a transplant, were excluded from this
      analysis. Response was defined as reaching complete independence from
      transfusions, relapse was defined as becoming again transfusion dependent. This
      criteria was validated by similar figures when using other 'relapse criteria'
      such as drop in neutrophil or platelet counts. Of 358 patients responding to IS.
      74 patients relapsed after a mean time of 778 d after treatment. The actuarial
      incidence of relapse is 35.2% at 14 years after IS. The risk for relapse was
      higher in patients responding within 120 d from IS (48%) compared to patients
      responding between 120 and 360 d (40%) and only 20% for slow responders (> 360 d
      from IS) (P < 0.00001). In multivariate analysis this factor still proved
      significant (P < 0.0001). The mean time between diagnosis and treatment was
      significantly longer in patients relapsing compared to patients who did not
      relapse (260 v 134 d, P = 0.037). Relapse was not predicted by the severity of
      the disease, age, and sex. In 39 of the 74 relapsing patients a second response
      could be achieved. Responses after relapse were associated in univariate analysis
      with early response to previous IS and early occurrence of relapse. The actuarial
      survival of patients not relapsing is significantly better than survival of
      patients relapsing (79.8% v 67.1%, P = 0.0024). However, the actuarial survival
      of 39 relapsing patients who responded again to IS was similar to patients not
      relapsing (86%) and significantly better than in 35 patients not reaching a
      second response after relapse (49.3%, P = 0.0015). This study indicates that
      relapse is a relevant problem in the treatment of aplastic anaemia, and does have
      an impact on overall survival. Prospective studies of immunosuppressive regimens,
      looking at responses, should also address this problem in the future.

PMID- 8280611
TI  - Abnormal erythrocyte band 4.1 protein in myelodysplastic syndrome with
      elliptocytosis.
AB  - A case of myelodysplastic syndrome with haemolytic anaemia and a marked
      elliptocytosis is reported. Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) of erythrocyte membrane proteins revealed that the
      patient's band 4.1 was decreased to about 50-70% of that of control and contained
      abnormal molecule migrating in a faster mobility than normal band 4.1, which was
      confirmed by immunoblotting. The actin/spectrin ratio of the patient's ghosts
      diminished to about 70% of that of control ghosts. Flowcytometric analysis showed
      that the glycophorin C content of the patient's erythrocytes was reduced but
      maintained the level of about 70% of that of normal, indicating that the
      glycophorin C-band 4.1 interaction might not be so seriously damaged as to cause
      elliptocytic shape change. We postulate that the abnormal band 4.1 produced from
      the abnormal erythroid clone may be the primary molecular defect and result in a
      dysregulation of spectrin-actin interaction to cause erythrocyte shape change and
      membrane instability.

PMID- 8280612
TI  - Subcellular distribution of desferrioxamine and hydroxypyridin-4-one chelators in
      K562 cells affects chelation of intracellular iron pools.
AB  - The interactions of iron chelators with intracellular iron pools have been
      examined by measuring the subcellular distribution of radiolabelled
      desferrioxamine (DFO) and the orally active hydroxypyridinone (HPO) chelator 1,2
      diethyl-3-hydroxypyridin-4-one (CP94), as well as the ability of these chelators
      to modify the subcellular distribution of 59Fe delivered by the receptor mediated
      endocytosis of transferrin. K562 cells were pulsed with 59Fe transferrin and
      challenged with DFO or CP94 (100 microM IBE) for 20 or 240 min and then subjected
      to subcellular fractionation. At 20 min there was a significant decrease (P <
      0.05) in both lysosomal/particulate 59Fe (75% of control) and cytosolic 59Fe
      ferritin (50% of control) in cells incubated with CP94, unlike cells treated with
      DFO where no decrease was observed. By 240 min, in addition to the above, 59Fe
      accumulation was significantly decreased in the nuclear, mitochondrial, and low
      molecular weight cytosolic fractions with CP94 (P < 0.05). With DFO a significant
      decrease in 59Fe in only the lysosomal/particulate and cytosolic ferritin
      compartments was observed at 240 min (P < 0.05). At this time, however, there was
      a significant accumulation of both cytosolic low molecular weight 59Fe and
      cytosolic DFO. The relatively rapid decrease of 59Fe within intracellular
      compartments seen with CP94 compared to DFO was paralleled by a significantly
      higher accumulation of CP94 than DFO in nuclear, lysosomal/particulate and low
      molecular weight cytosolic compartments at 20 min (P < 0.05). These results
      suggest that transferrin derived endosomal iron may be chelated by HPOs, unlike
      DFO, due to their faster uptake into these organelles. The more rapid access of
      HPOs than DFO to certain intracellular iron pools may explain the greater
      possibility of HPOs to inhibit proliferation of cells in vivo.

PMID- 8280613
TI  - Gaucher disease mutations in non-Jewish patients.
AB  - The DNA from 64 non-Jewish patients with Gaucher disease was examined for 29
      different glucocerebrosidase mutations that are known to cause the disease. The
      most common was mutation 1448C and the second most common 1226G. Twenty of the
      mutations remained unidentified. These results were compared to those obtained
      from 122 Jewish patients, in whom the most common mutations were 1226G and 84GG.
      Among the non-Jewish patients 15.6% of the mutations remained unidentified, while
      among the Jewish patients only 1.2% remained unidentified, and even screening for
      the five most common mutations identified all but 2.9% of the Jewish mutations.
      The greater diversity of mutations among the non-Jewish patients has important
      implications with respect to DNA-based screening, diagnosis and counselling.

PMID- 8280614
TI  - A trial of recombinant human superoxide dismutase in patients with Fanconi
      anaemia.
AB  - Fanconi anaemia (FA) is a rare genetic disorder that predisposes to the
      development of aplastic anaemia and neoplasia. The pathophysiologic hallmark of
      FA is increased susceptibility to chromosomal breakage. Superoxide metabolism has
      also been shown to be involved in the cellular pathophysiology of FA. Human SOD
      (rh-SOD), an enzyme which dismutates superoxide, has recently been cloned and
      expressed in yeast. We treated four FA patients with a 2-week infusion of rh-SOD
      (25 mg/kg d daily) to determine whether rh-SOD had any effect on haemopoietic
      progenitor cell growth or on the abnormal cellular phenotype. We found that
      lymphocyte chromosomal aberrations induced by diepoxybutane were decreased during
      rh-SOD treatment in two patients and that bone marrow progenitors were increased
      in one patient.

PMID- 8280616
TI  - Contamination of peripheral blood by monoclonal B cells following treatment of
      multiple myeloma by high-dose chemotherapy.
AB  - Peripheral blood samples obtained from five patients with multiple myeloma, after
      high-dose chemotherapy, were studied for monoclonal B plasma cell contamination.
      We used the technique of immunoglobulin heavy chain gene 'fingerprinting' at the
      time of diagnosis and during apheresis. The level of sensitivity of this
      technique is between 0.01% and 0.001% in two patients in whom a monoclonal
      population was detected in peripheral blood.

PMID- 8280615
TI  - Reversing of chlorambucil resistance by ethacrynic acid in a B-CLL patient.
AB  - We evaluated the reversing activity of ethacrynic acid in a B-CLL patient
      resistant to chlorambucil. The glutathione S-transferase (GST) activity, measured
      in peripheral blood lymphocytes, resulted extremely elevated. Ethacrynic acid, at
      pharmacological concentrations, partially reversed chlorambucil resistance and
      this result appeared related to the increased GST levels.

PMID- 8280617
TI  - Spontaneous remission of acute adult T-cell leukaemia with chromosomal
      abnormality infiltrating to skin and liver.
AB  - Acute type of adult T-cell leukaemia (ATL) has been recognized as highly
      progressive T-cell malignancy with a median survival of 7 months. We present a
      case who had a spontaneous remission from acute type ATL with organ involvement
      and chromosomal abnormality implying very poor prognosis. Although the mechanism
      of spontaneous remission remains uncertain, our case was unique with regard to
      the progression and regression of leukaemia.

PMID- 8280618
TI  - Fragile X syndrome and myelodysplasia discovered during pregnancy.
AB  - We describe a female patient who presented at pregnancy with leucopenia and was
      found to suffer from both fragile X syndrome [Fra(X)] and myelodysplastic
      syndrome with cytogenetic abnormalities in bone marrow cells including 4q+ and
      deletion D13. To date only four cases of Fra(X) syndrome with malignant tumours
      (one haematological), all in male patients, have been reported. We believe that
      the occurrence of the myelodysplastic syndrome in this patient could be more than
      coincidental.

PMID- 8280619
TI  - Replacement of HLA class II serology by the HLA-DR microtitre plate oligotyping
      assay: a one-year experience in unrelated bone marrow donor selection.
AB  - Because the selection of unrelated bone marrow donors requires a more accurate
      HLA-typing technique than is used for sibling donors, we have replaced class II
      serology by a rapid and highly discriminative HLA-DR DNA oligotyping assay on
      microtitre plates. We present here our 1-year experience with class II typing for
      112 potential donors identified for 33 consecutive leukaemic patients. Although
      the donors were selected to be HLA-A, -B, -DR serologically identical, the
      microtitre plate oligotyping assay detected DR incompatibilities in 52.7% of the
      patient/donor pairs. One third was due to incorrect or incomplete typing of DR11
      to DR16, the others to mismatches for the serologically indistinguishable
      subtypes of DR1, 11, 13 and 15, known to be relevant for T cell recognition.

PMID- 8280620
TI  - Fechtner syndrome: report of a third family and literature review.
AB  - We observed macrothrombocytopenia with leucocyte inclusions in 10 out of 14
      members of a four-generation family. Morphological features of leucocyte
      inclusions and the presence of Alport-related symptoms supported the diagnosis of
      Fechtner syndrome. Compared to the two previously reported Fechtner families, our
      kindred showed reduced expression of Alport manifestations. These, in members
      aged less than 50, were represented by clinically silent ocular abnormalities.
      Due to the frequent non-recognition of macrothrombocytopenia. Fechtner variants
      with low penetrance might be difficult to diagnose. In addition, Sebastian
      syndrome, recently distinguished from Fechtner disease in lacking Alport
      manifestations, might be one of these variants.

PMID- 8280621
TI  - Overexpression of PRAD1 in a mantle zone lymphoma patient with a
      t(11;22)(q13;q11) translocation.
AB  - The PRAD1 gene identified from the chromosome band 11q13 region was previously
      demonstrated to be overexpressed in cell lines with t(11;14)(q13;q32)
      translocation and was suggested to be a candidate BCL-1 gene. We report here one
      case of mantle zone lymphoma with a t(11;22)(q13;q11), a variant translocation at
      the BCL-1 locus, having the PRAD1 overexpression. By analogy with the c-myc gene
      in Burkitt's lymphoma and the BCL-2 gene in follicular lymphoma, this case
      supports strongly the idea that the PRAD1 is the candidate BCL-1 gene.

PMID- 8280622
TI  - Deaths in patients receiving oral iron chelator L1.

PMID- 8280623
TI  - Detection and accurate sizing of PCR product by automated scanning: improved
      detection of immunoglobulin gene rearrangements in ALL.

PMID- 8280624
TI  - Acute promyelocytic leukaemia developing into acute myeloblastic leukaemia.

PMID- 8280625
TI  - Incidence of cancer and exposure to toluene diisocyanate and methylene
      diphenyldiisocyanate: a cohort based case-referent study in the polyurethane foam
      manufacturing industry.
AB  - OBJECTIVE: To assess the association between occupational exposure to toluene
      diisocyanate or methylene diphenyldiisocyanate and risk of cancer. DESIGN: A
      cohort based case-referent study. STUDY BASE: 7023 subjects employed during the
      period 1958 to 1987 in nine Swedish polyurethane foam manufacturing plants. MAIN
      OUTCOME MEASURES: Odds ratios adjusted with respect to the matching factors (age
      at risk, calendar year at risk, sex, and plant), calculated from the conditional
      logistic regression model. RESULTS: A non-significant association was found
      between high exposure to isocyanates and prostate cancer (OR 2.66, 90% confidence
      interval (90% CI) 0.39-18.1), which was not enhanced when an induction latency
      period of 10 years was applied. An association between isocyanate exposure and
      colon cancer was even weaker. No associations were seen for non-Hodgkin's
      lymphoma and rectal cancer. CONCLUSIONS: The tentative associations, derived from
      a previous cohort study, between isocyanate exposure and excess risk for non
      Hodgkin's lymphoma and rectal cancer were not supported. Instead, non-significant
      associations with prostate cancer, and possibly colon cancer, were seen.

PMID- 8280626
TI  - Mortality and incidence of cancer among a cohort of self employed butchers from
      Geneva and their wives.
AB  - To investigate whether specific cancers are associated with the occupation of
      butcher, as has been reported from other countries, a historical prospective
      cohort study was undertaken. The cohort consisted of all self employed butchers
      (n = 552) and pork butchers (n = 310) born since 1880 who set up a shop in the
      canton of Geneva from 1901 to 1969, and of their wives (n = 887). The study group
      was followed up from 1901 to 1990 for general mortality, from 1942 to 1990 for
      cause specific mortality, and from 1970 to 1989 for incidence of cancer. There
      was no trace of 45 men (5%) and 52 women (6%). Compared with the general
      population of the canton of Geneva, butchers and pork butchers experienced a
      significant increase, taking into account 15 years of latency, in mortality from
      all causes (observed deaths (Obs) 540, expected deaths (Exp) 445.5, standardised
      mortality ratio (SMR) 121, 90% confidence interval (90% Cl) 113-130). There were
      significant excesses in incidence and mortality from colorectal cancer, cancer of
      the prostate, and all malignant neoplasms, and in incidence of cancer of the
      liver. The risk of lung cancer was significantly increased among pork butchers
      (SMR 176, 90% Cl 114-262; standardised incidence ratio (SIR) 231, 90% Cl 137-368)
      but not among butchers (SMR 92, 90% Cl 59-138; SIR 113, 90% Cl 67-179). There was
      also a significant increase in mortality from cancer of the larynx among
      butchers. For non-malignant causes of death significant excesses were found among
      all men for ischaemic heart disease, motor vehicle accidents, and cirrhosis of
      the liver. Analysis of subgroups showed a cluster of deaths from leukaemia among
      older butchers born between 1880 and 1899 (Obs 5, Exp 0.6, p < 0.0001). Exposure
      of pork butchers to polycyclic aromatic hydrocarbons during meat smoking, which
      was assessed in a contemporary study, might have contributed to their increased
      risk of lung cancer. The possible role of other factors, especially cigarette
      smoking, nitrosamines, and oncogenic viruses was discussed. Moreover, there was
      evidence from another contemporary study that butchers and pork butchers ate more
      animal fat, and probably more animal protein, than the average male population of
      Geneva. These results suggest that dietary factors could be implicated in the
      excesses of colorectal cancer, cancer of the prostate, and ischaemic heart
      disease. An increased risk for alcohol abuse might explain the excesses of liver
      cirrhosis, cancer of the liver, cancer of the larynx and motor vehicle accidents.
      Among all wives overall mortality was similar to that expected (SMR 100, 90% Cl
      93-108) and there was no significant excess risk for any specific cancer nor for
      any non-malignant cause of death. Results for cancer of the cervix uteri,
      especially among subgroups, suggest an increased risk consistent with previous
      findings from other countries.

PMID- 8280627
TI  - Mortality of iron miners in Lorraine (France): relations between lung function
      and respiratory symptoms and subsequent mortality.
AB  - An increased mortality from lung and stomach cancer was found in previous studies
      on Lorraine iron miners. A detailed analysis, however, was not possible due to
      the lack of data for survivors. In this study the cohort included 1178 workers
      selected at random from all the 5300 working miners aged between 35 and 55 at the
      start of the follow up period, which ranged from 1975 to 1985. Occupational
      exposures and tobacco consumption, lung function tests, and respiratory symptoms
      were assessed for each subject in 1975, 1980, and 1985. This study confirmed the
      excess of lung cancer (standardised mortality ratio (SMR) = 389, p < 0.001) and
      of stomach cancer (SMR = 273, p < 0.05). There was no excess of lung cancer in
      non-smokers and moderate smokers (< 20 pack-years) or the miners who worked only
      at the surface or underground for less than 20 years. A significant excess (SMR =
      349, p < 0.001) was found in moderate smokers when they worked underground for
      between 20 and 29 years. Heavy smokers (over 30 pack-years) or subjects who
      worked underground for more than 30 years experienced a high risk: SMR = 478 (p <
      0.001) for moderate smokers who worked underground for over 30 years; 588 (p <
      0.001) for heavy smokers who worked underground for between 20 and 29 years; and
      877 (p < 0.001) for heavy smokers who worked underground for over 30 years. This
      showed an interaction between smoking and occupational exposure. The excess
      mortality from lung cancer was because there were some subjects who died young
      (from 45 years old). Comparison with the results of a previous study showed that
      additional hazards produced by diesel engines and explosives increased the
      mortality from lung cancer. The SMR was higher than 400 (p < 0.001) from 45 years
      old instead of from 56 years. A relation was found between a decrease in vital
      capacity (VC), forced expiratory volume in one second (FEV1) and of FEV1/VC and
      mortality from all causes and from lung cancer in heavy smokers or men who had
      worked underground for more than 20 years. Respiratory symptoms were related to
      mortality from lung cancer among smokers (moderate and heavy) who worked
      underground for more than 20 years. It is considered that the risk of lung cancer
      in the Lorraine iron miners was mainly due to dust, diesel engines, and
      explosives although the role of low exposure to radon daughters could not be
      totally excluded.

PMID- 8280628
TI  - Analysis of ferruginous bodies in bronchoalveolar lavage from foundry workers.
AB  - Classical ferruginous bodies in tissue samples are considered to be markers of
      past exposure to asbestos. Recent studies have shown that the presence of
      ferruginous bodies in bronchoalveolar lavage (BAL) fluid correlates with past
      exposure to asbestos and offers a more sensitive reference than occupational
      history. Lavage samples from five subjects who had worked in foundries were
      evaluated by light microscopy for the presence of ferruginous bodies and by
      transmission electron microscopy for both characterisation of the uncoated fibre
      burden and analysis of the cores of the ferruginous bodies. All samples at lower
      magnification (light microscopy (200 x)) contained ferruginous bodies that were
      externally consistent with asbestos bodies. At higher magnification (400 x), a
      separate population from this group could be identified by the presence of a thin
      black ribbon. Transmission electron microscopy of the core materials of
      ferruginous bodies and comparable uncoated particulates supported the reliability
      of higher magnification light microscopy for distinguishing most of those non
      asbestos cores; however, a population of transparent non-asbestos cored
      ferruginous bodies were also shown to exist.

PMID- 8280629
TI  - Study of occupational lung cancer in asbestos factories in China.
AB  - A retrospective cohort study (1972-81) of occupational cancers in asbestos
      (chrysotile) factories has been previously published. In this paper the results
      of continued tracing and interviewing of members of this cohort from 1982 to 1986
      is reported. The cohort included 5893 persons (45,974 person-years for men and
      39,445 person-years for women). Malignant tumours played a large part in causes
      of death (36.9%). There were 183 cancers and 67 lung cancers among 496 deaths.
      The mortality due to lung cancer had a tendency to increase. By comparison with a
      control group, the RR of lung cancer was 5.32 (p < 0.01), and the SRR of lung
      cancer was 4.2 (p < 0.01), significantly higher than those of a control group.
      Among 148 cases of death from asbestosis there were 33 cases complicated with
      lung cancer (22.3%). The dose-response relations between exposure to asbestos and
      incidence of asbestosis and lung cancer were also studied in one asbestos
      factory. There was a positive correlation. A synergistic effect was found between
      cigarette smoking and lung cancer. Preventive and control measures and exposure
      limits for asbestos dust in the air of workplaces were recommended.

PMID- 8280630
TI  - Contact allergens in registered cleaning agents for industrial and household use.
AB  - Cleaning work is a common cause of both irritant and allergic contact dermatitis.
      Cleaning agents for industrial and household use are registered in the Danish
      Product Register Data Base (PROBAS) according to a special notification rule
      issued by the Danish Environmental Protection Agency. About 2350 registered
      washing and cleaning agents containing about 1250 different chemical substances
      were marketed in Denmark in February 1992. The occurrence of 49 contact allergens
      in 16 different product types within washing and cleaning agents were listed.
      Preservatives and surface active agents made up the main part of contact
      allergens. Isothiazolinones and formaldehyde releasers were the most commonly
      registered preservatives, and coconut diethanolamide the most commonly registered
      surface active agent. The major product types registered as containing contact
      allergens were general cleaners, skin cleaners, hair shampoos, and floor
      polishes.

PMID- 8280631
TI  - Coal mining, emphysema, and compensation revisited.

PMID- 8280632
TI  - Pulmonary effects of exposure to fine fibreglass: irregular opacities and small
      airways obstruction.

PMID- 8280633
TI  - Semen quality in welders exposed to radiant heat.

PMID- 8280634
TI  - Hazards of deep-sea fishing. 1971.

PMID- 8280635
TI  - Ethylene oxide: an assessment of the epidemiological evidence on carcinogenicity.
AB  - Mortality from cancer among workers exposed to ethylene oxide (EtO) has been
      studied in 10 distinct cohorts that include about 29,800 workers and 2540 deaths.
      This paper presents a review and meta-analysis of these studies, primarily for
      leukaemia, non-Hodgkin's lymphoma, stomach cancer, pancreatic cancer, and cancer
      of the brain and nervous system. The magnitude and consistency of the
      standardised mortality ratios (SMRs) were evaluated for the individual and
      combined studies, as well as trends by intensity or frequency of exposure, by
      duration of exposure, and by latency (time since first exposure). Exposures to
      other workplace chemicals were examined as possible confounder variables. Three
      small studies by Hogstedt initially suggested an association between EtO and
      leukaemia, but in seven subsequent studies the SMRs for leukaemia have been much
      lower. For the combined studies the SMR = 1.06 (95% confidence interval (95% CI)
      0.73-1.48). There was a slight suggestion of a trend by duration of exposure (p =
      0.19) and a suggested increase with longer latency (p = 0.07), but there was no
      overall trend in risk of leukaemia by intensity or frequency of exposure; nor did
      a cumulative exposure analysis in the largest study indicate a quantitative
      association. There was also an indication that in two studies with increased
      risks the workers had been exposed to other potential carcinogens. For non
      Hodgkin's lymphoma there was a suggestive risk overall (SMR = 1.35, 95% CI 0.93
      1.90). Breakdowns by exposure intensity or frequency, exposure duration, or
      latency did not indicate an association, but a positive trend by cumulative
      exposure (p = 0.05) was seen in the largest study. There was a suggested increase
      in the overall SMR for stomach cancer (SMR = 1.28, 95% CI 0.98-1.65 (CI 0.73-2.26
      when heterogeneity among the risk estimates was taken into account)), but
      analyses by intensity or duration of exposure or cumulative exposure did not
      support a causal association for stomach cancer. The overall SMRs and exposure
      response analyses did not indicate a risk from EtO for pancreatic cancer (SMR =
      0.98), brain and nervous system cancer (SMR = 0.89), or total cancer (SMR =
      0.94). Although the current data do not provide consistent and convincing
      evidence that EtO causes leukaemia or non-Hodgkin's lymphoma, the issues are not
      resolved and await further studies of exposed populations.

PMID- 8280636
TI  - Mortality study of workers employed at a plant manufacturing chemicals for the
      rubber industry: 1955-86.

PMID- 8280637
TI  - Dust exposure and mortality in chrysotile mining, 1910-75. 1980.

PMID- 8280638
TI  - The 1891-1920 birth cohort of Quebec chrysotile miners and millers: mortality
      1976-88.
AB  - A cohort of some 11,000 men born 1891-1920 and employed for at least one month in
      the chrysotile mines and mills of Quebec, was established in 1966 and has been
      followed ever since. Of the 5351 men surviving into 1976, only 16 could not be
      traced; 2508 were still alive in 1989, and 2827 had died; by the end of 1992 a
      further 698 were known to have died, giving an overall mortality of almost 80%.
      This paper presents the results of analysis of mortality for the period 1976 to
      1988 inclusive, obtained by the subject-years method, with Quebec mortality for
      reference. In many respects the standardised mortality ratios (SMRs) 20 years or
      more after first employment were similar to those for the period 1951-75--namely,
      all causes 1.07 (1951-75, 1.09); heart disease 1.02 (1.04); cerebrovascular
      disease 1.06 (1.07); external causes 1.17 (1.17). The SMR for lung cancer,
      however, rose from 1.25 to 1.39 and deaths from mesothelioma increased from eight
      (10 before review) to 25; deaths from respiratory tuberculosis fell from 57 to
      five. Among men whose exposure by age 55 was at least 300 million particles per
      cubic foot x years (mpcf.y), the SMR (all causes) was elevated in the two main
      mining regions, Asbestos and Thetford Mines, and for the small factory in
      Asbestos; so were the SMRs for lung cancer, ischaemic heart disease,
      cerebrovascular disease, and respiratory disease other than pneumoconiosis.
      Except for lung cancer, however, there was little convincing evidence of
      gradients over four classes of exposure, divided at 30, 100, and 300 mpcf.y. Over
      seven narrower categories of exposure up to 300 mpcf.y the SMR for lung cancer
      fluctuated around 1.27 with no indication of trend, but increased steeply above
      that level. Mortality form pneumoconiosis was strongly related to exposure, and
      the trend for mesothelioma was not dissimilar. Mortality generally was related
      systematically to cigarette smoking habit, recorded in life from 99% of survivors
      into 1976; smokers of 20 or more cigarettes a day had the highest SMRs not only
      for lung cancer but also for all causes, cancer of the stomach, pancreas, and
      larynx, and ischaemic heart disease. For lung cancer SMRs increased fivefold with
      smoking, but the increase with dust exposure was comparatively slight for non
      smokers, lower again for ex-smokers, and negligible for smokers of at least 20
      cigarettes a day; thus the asbestos-smoking interaction was less than
      multiplicative. Of the 33 deaths from mesothelioma in the cohort to date, 28 were
      in miners and millers and five were in employees of a small asbestos products
      factory where commercial amphiboles had also been used. Preliminary analysis also
      suggest that the risk of mesothelioma was higher in the mines and mills at
      Thetford Mines than in those at Asbestos. More detailed studies of these
      differences and of exposure-response relations for lung cancer are under way.

PMID- 8280639
TI  - Respiratory health effects of carbon black: a survey of European carbon black
      workers.
AB  - A study population of 3086 employees was identified in 18 carbon black production
      plants in seven European countries. Respiratory health questionnaires,
      spirometry, and chest radiographs were used to estimate effects on health and
      personal monitoring procedures were employed to measure current exposure to
      inspirable and respirable dust along with sulphur and carbon monoxide. The low
      concentrations of gaseous contaminants made the generation of their current and
      cumulative exposure indices impossible. Low responses from some plants restricted
      the final analysis to 1742 employees in 15 plants (81% response rate) for
      respiratory symptoms and spirometry, and 1096 chest radiographs from 10 plants
      (74% response rate). In total, 1298 respirable and 1317 inspirable dust samples,
      as well as 1301 sulphur dioxide and 1322 carbon monoxide samples were collected.
      This study is the first to include a comprehensive and concurrent assessment of
      occupational exposure to carbon black dust and its associated gaseous
      contaminants. Cough, sputum, and the symptoms of chronic bronchitis were found to
      be associated with increasing indices of current exposure. Lung function tests
      also showed small decreases in relation to increasing dust exposure in both
      smokers and non-smokers. Nearly 25% of the chest radiographs showed small
      opacities of category 0/1 or greater. These were strongly associated with indices
      of cumulative dust exposure. The findings are consistent with a non-irritant
      effect of carbon black dust on the airways combined with dust retention in the
      lungs. Further cross sectional studies are planned to investigate whether long
      term exposure to carbon black dust causes damage to the lung parenchyma.

PMID- 8280640
TI  - Incidence of cancer among welders of mild steel and other shipyard workers.
AB  - The incidence of cancer among 4571 shipyard workers with first employment between
      1940 and 1979, including 623 welders of mild steel, was investigated in a
      historical cohort study. The loss to follow up was 1.1%. The total number of
      deaths was 1078 (974.5 expected) and there were 408 cases of cancer v 361.3
      expected. Sixty five cases of lung cancer were found v 46.3 expected based on the
      national rates for males. Four pleural mesotheliomas had occurred (1.2 expected),
      none among the welders. An excess of lung cancers was found among the welders
      (nine cases v 3.6 expected). There were six cases of lung cancer v 1.6 expected
      in a high exposure group of 255 welders. A survey of the smoking habits as of
      1984 indicated 10%-20% more daily smokers among the shipyard production workers
      than among Norwegian males. Exposure to smoking and asbestos were confounding
      variables in this study.

PMID- 8280641
TI  - Serum laminin, hydrocarbon exposure, and glomerular damage.
AB  - It has been postulated that occupational exposure to hydrocarbons may damage the
      kidney and lead to glomerulonephritis and chronic renal failure. As laminin is a
      ubiquitous basement membrane component that seems to play a central part in the
      structure and function of basement membranes and as the normal renal filtration
      process is highly dependent on an intact glomerular basement membrane, the serum
      laminin concentration was examined in a population of workers exposed to
      hydrocarbons. The hydrocarbon exposure was assessed by exposure surrogates
      (exposure duration and exposure score). An interaction between occupational
      exposure to hydrocarbons and hypertension increased the laminin concentration
      whereas the laminin concentration decreased in workers exposed for a long time
      probably because of a selection effect. In a subgroup of printers exposed to
      toluene whose hippuric acid excretion had been recorded for several years this
      interaction was confirmed when the hippuric acid excretion was substituted for
      the other exposure indices. In the exposed group, the age-related decline in
      creatinine clearance was accelerated. These results seem to confirm that
      occupational exposure to hydrocarbons is a non-specific factor that may promote a
      deterioration of renal function.

PMID- 8280642
TI  - Biological monitoring of occupational exposure to toluene diisocyanate:
      measurement of toluenediamine in hydrolysed urine and plasma by gas
      chromatography-mass spectrometry.
AB  - Exposure to toluene diisocyanate (TDI) was studied during 48 hours and biological
      samples from nine subjects were taken in a factory producing flexible
      polyurethane (PUR) foam. Five PUR workers, two white collar workers, and two
      volunteers were studied. The concentrations of TDI in air were determined by high
      performance liquid chromatography with the 9-(N-methylaminomethyl)-anthracene
      reagent. Urine and plasma samples were collected and the TDI related amines, 2,4
      toluenediamine (2,4-TDA) and 2,6-toluenediamine (2,6-TDA), were determined (after
      hydrolysis) as pentafluoropropionic anhydride (PFPA) derivatives by capillary gas
      chromatography-mass spectrometry (GC-MS) with selected ion monitoring (SIM) in
      the negative chemical ionisation mode. The concentration of TDI in air was 1%-10%
      of the Swedish threshold limit value (TLV) of 40 micrograms/m3. The ratio between
      2,4-TDI and 2,6-TDI varied in the air samples in the range of 60%:40%-5%:95%.
      Calibration plots for human urine spiked with 2,6-TDA and 2,4-TDA in the range of
      0.2-12 micrograms/l were produced on eight different occasions during five weeks.
      The SDS of the calibration plot slopes (n = 8) were less than 4%. Urine and blood
      samples were taken on six occasions for eight of the studied subjects and on four
      occasions for one subject during a two day period. The five male PUR workers
      showed the highest average urinary elimination rate of TDA. Two PUR workers and
      the two white collar workers had an elimination rate of 20-70 ng on average for
      the sum of 2,6-TDA and 2,4-TDA per hour and three PUR workers had an average of
      100-300 ng TDA per hour. The elimination rate curves for all the studied subjects
      had a linear relation with exposure to TDI. The concentrations of 2,4-TDA and 2,6
      TDA in plasma for the PUR factory employees were virtually stable. No relation
      between the elimination rates of TDA in urine and plasma concentrations of TDA
      was found. The five PUR workers showed plasma concentrations of the sum of 2,4
      TDA and 2,6-TDA in the range 1-8 ng per ml. The two white collar workers, present
      only on occasions in the factory, had 0.2- ng TDA per ml plasma. The two
      volunteers showed an increasing concentration of TDA in plasma with time. At the
      end of the study their plasma concentrations were 0.6 ng/ml and 0.2 ng/ml plasma.
      Three subjects had the same concentration of the two TDA isomers in plasma, two
      subjects had about double, and two subjects had 12 times higher concentrations of
      2,6-TDA than 2,4-TDA. The presented study indicates that it is possible to
      monitor exposure to TDI by monitoring plasma concentrations of TDA.

PMID- 8280643
TI  - Plumboporphyria (ALAD deficiency) in a lead worker: a scenario for potential
      diagnostic confusion.
AB  - A lead worker developed bilateral wrist drop. At first this seemed to be a lead
      neuropathy but all his screening tests for blood and urine toxicity had been
      within the accepted safety limit during employment. Detailed investigation showed
      that he had plumboporphyria (ALAD deficiency) which had been symptom free until
      he was exposed to lead. Details of his porphyrin metabolism are presented.

PMID- 8280644
TI  - Bias.

PMID- 8280645
TI  - Misconceptions about blood lead concentrations.

PMID- 8280646
TI  - An epidemiological study of workers potentially exposed to ethylene oxide.

PMID- 8280647
TI  - Neuropsychological performance and solvent exposure among car body repair shop
      workers.

PMID- 8280648
TI  - 'Gene of the year' p53: when will it show clinical promise?

PMID- 8280649
TI  - Towards improved endocrine therapy for advanced breast cancer.

PMID- 8280650
TI  - Is a bio-psycho-social approach in cancer research feasible?

PMID- 8280651
TI  - The teaching of clinical oncology in Italian medical schools. A survey among
      teachers and students.
AB  - BACKGROUND: Oncologists, health care workers and health organizations consider
      well-performed teaching programs in clinical oncology a fundamental step in
      cancer control. The aim of our study was to assess the views of teachers and
      students on the present status of oncology teaching in Italian medical schools
      and on the most common shortcomings in cancer education. MATERIALS AND METHODS: A
      survey was carried out among teachers and students of 17 Italian medical schools
      using two different questionnaires. Six hundred forty-seven students of Northern,
      Central and Southern Italy in the final two years (5th and 6th) of their medical
      curriculum and 87 professors of pathology, surgery, internal medicine and medical
      oncology completed the questionnaires. RESULTS: Doctor/patient relationships and
      integration among disciplines were the most unsatisfactory aspects of oncology
      teaching, according to students. Biology, epidemiology, radiotherapy, and medical
      treatment were felt to be insufficiently treated, whilst diagnostic aspects,
      clinical management and surgery were rated sufficient. The median number of
      cancer patients to whom each student had access during his/her training was
      limited, averaging only 13 patients; however, a high degree of variability was
      noted. A larger number of patients was generally observed in smaller, less
      crowded medical schools, with notable exceptions. Although the majority of
      teachers had clinical practices related to their disciplines, only a small number
      of students underwent a period of clinical training. Traditional methods of
      teaching were preferred to innovative methods, while interaction among
      disciplines was uncommon. CONCLUSIONS: This survey emphasizes the dualism between
      students' expectations and teachers' ideas about cancer teaching. Doctor/patient
      relationships and poor attention to practical clinical problems seem the most
      critical issues for clinical oncology training in Italian medical schools.

PMID- 8280652
TI  - Protracted drug infusions in cancer treatment: an appraisal of 5-fluorouracil,
      doxorubicin, and platinums.
AB  - The feasibility to deliver chemotherapeutic agents by protracted i.v. infusion
      has greatly increased in the recent past. Indwelling ports, longer lasting
      central venous catheters requiring less than daily maintenance 'flushing',
      surgical expertise in placement, use in analgesia and nutrition, and 'smart' pump
      technology have all contributed to their increasing popularity. Justification for
      use of infusions in cancer chemotherapy has been slow in appearing with few
      studies proceeding to the comparative stage. This review will focus on three
      drugs in common use in cancer treatment, with the purpose of appraising the role
      of such infusions in cancer therapeutics and of deriving some lessons that might
      be applicable to other drugs or to drug development in general. For fluorouracil
      and doxorubicin the rationale and clinical findings favoring further development
      of infusion regimens is particularly strong. In the case of platinum compounds,
      some toxicologic advantages have emerged, but other measures designed to protect
      against the toxicities of cisplatin compete with infusion regimens in this
      regard. The therapeutic potential for this form of drug delivery, therefore,
      appears still confined to a subset of patients. Stronger rationales for the use
      of protracted infusions may be forthcoming from pharmacodynamic findings as in
      the case of etoposide, combined modality therapy with radiation for FU and
      cisplatin, biochemical modulation for FU, and reversal of multidrug resistance
      and its modulation for doxorubicin. While awaiting research into these areas of
      clinical and pre-clinical investigations, the role of infusion appears most
      evident in the cardiotoxicity protection of anthracyclines, and in further
      efficacy exploration (through dose or modulation) of FU. Both mechanistic and
      pharmacologic considerations could also provide additional stimulus for
      development of new formulations such as long circulating liposomes, and drugs
      more suitable for oral administration.

PMID- 8280653
TI  - Primary endocrine therapy for advanced breast cancer: to start with tamoxifen or
      with medroxyprogesterone acetate?
AB  - BACKGROUND: The availability of compounds effective against metastatic disease
      and at the same time excellently tolerated even in long-term administration has
      determined the choice of tamoxifen as primary treatment for palliation in
      metastatic breast cancer. Other drugs or other hormonal approaches were hardly
      tested against tamoxifen, especially as first-line treatment. PATIENTS AND
      METHODS: 119 patients with metastatic breast cancer and no prior endocrine
      therapy were randomized to receive either tamoxifen (TAM) 20 mg/day orally (64
      patients), or medroxyprogesterone acetate (MAP) 1g/day i.m. 5 days/week for 4
      weeks and then 500 mg twice a week (55 patients). The subsequent endocrine
      therapy was also prospectively defined at study entry. RESULTS: A total of 111
      events, contributing to the endpoint 'time to progression' have so far been
      observed: a study of similar size would have a 90% power to detect a hazard ratio
      of 1.85. Initial MAP was associated with a significantly higher remission rate
      (50% versus 30% for tamoxifen; p = 0.023) and a marginally significantly longer
      median time to progression (8.8 versus 5.4 months; p = 0.051). Overall survival
      was also longer for the MAP group (28 versus 20 months; p = 0.384). The use of
      MAP was associated with a significantly higher toxicity, mainly hypertension,
      weight gain and tremor. CONCLUSIONS: The implications of these results are that
      initial endocrine therapy in postmenopausal patients with metastatic disease
      should be MAP if the patient is willing to accept the side effects of high-dose
      progestins. Progestins should be tested in the adjuvant setting for
      postmenopausal women, especially those with no tendency to hypertension or
      obesity.

PMID- 8280654
TI  - Randomized comparison of the effects of tamoxifen, megestrol acetate, or
      tamoxifen plus megestrol acetate on treatment response and survival in patients
      with metastatic breast cancer.
AB  - BACKGROUND: The antioestrogen tamoxifen and progestins act via different
      receptors and may therefore have complementary effects against human breast
      cancer. This possibility was tested in a randomized study which compared the
      effects of tamoxifen, standard-dose megestrol acetate, and these two agents in
      combination, in patients with metastatic breast cancer. PATIENTS AND METHODS: 184
      post-menopausal patients with metastatic breast cancer were randomized to initial
      treatment with either tamoxifen (TAM) 40 mg daily, megestrol acetate (MA) 160 mgm
      daily, or the combination of the two administered simultaneously. Patients
      crossed over to the alternative single agent on relapse or disease progression.
      Patients were evaluated for response, time to initial and ultimate treatment
      failure, and survival. RESULTS: There were no significant differences between the
      three groups with respect to response rates, nor the other parameters. Patient
      survival was significantly associated with age > 60 years, ER positive status,
      and the absence of visceral metastases. CONCLUSIONS: TAM and MA are both equally
      effective in response induction as initial treatments and the combination has no
      advantage. Sequential treatment is still optimal, TAM being the preferred initial
      agent in view of the reported side effects with MA.

PMID- 8280655
TI  - Familial cancer, emotional distress, and low natural cytotoxic activity in
      healthy women.
AB  - BACKGROUND: We investigated the possibility that healthy individuals with a
      family history of cancer may have lower levels of natural cytotoxic activity and
      examined the possible contribution of distress-induced immune suppression.
      MATERIALS AND METHODS: Forty-three healthy women, recruited without regard to
      their family histories of cancer, came to the laboratory on two consecutive days.
      On each day, subjects completed questionnaires and provided blood samples for
      assessment of natural cytotoxic activity. RESULTS: 1) Women with a history of
      cancer in one or more first degree relatives had lower levels of natural
      cytotoxic activity than women without cancer in first degree relatives. 2) There
      were no differences in demographic, health, or behavioral variables, but we could
      not rule out differences in emotional distress. 3) Independent of family history,
      women with higher levels of distress had lower natural cytotoxic activity. 4)
      When the contribution of this distress-induced immune suppression was
      statistically removed, natural cytotoxic activity remained lower in women with
      cancer in first degree relatives. CONCLUSIONS: These findings raise the
      possibility that reductions in systemic natural cytotoxic activity, in
      conjunction with heritable defects in the preneoplastic cell, may contribute to
      increased cancer risk in individuals with a family history of cancer.

PMID- 8280656
TI  - 5-Fluorouracil, folinic acid, epidoxorubicin and cisplatin (FLEP) combination
      chemotherapy in advanced measurable gastric cancer. A phase II trial of the
      Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD).
AB  - BACKGROUND: Metastatic disease is a common problem in gastric cancer and the
      development of better chemotherapeutic regimens is a clear priority in
      gastrointestinal oncology. PATIENTS AND METHODS: Ninety consecutive, previously
      untreated patients with unresectable or measurable metastatic gastric cancer were
      included in a multicenter phase II trial with a combination of folinic acid (200
      mg/m2) and 5-fluorouracil (400 mg/m2) days 1-3, with epidoxorubicin (60 mg/m2)
      and cisplatin (100 mg/m2) on day 2. RESULTS: A total of 376 courses of FLEP were
      given, with a median of four courses per patient. Objective responses were
      observed in 32 (35%) patients (CI at 95%: 25.7%-46.3%). Eight (9%) patients
      experienced clinical complete remissions. Median time to progression was 25 weeks
      for the entire group of patients and 38 weeks for responders. Myelosuppression
      was the primary toxicity. WHO grade 3 leukopenia appeared in 26 patients (29%).
      Ten presented episodes of febrile neutropenia requiring hospitalization, but no
      toxic deaths were observed. Grades 3 and 4 thrombocytopenia were seen in 8 and 1
      patients, respectively. Median survival time was 8 months for all treated
      patients and 11 months for responders. CONCLUSIONS: The FLEP regimen is an active
      combination in advanced gastric cancer with moderate toxicity that warrants
      further testing in a phase III trial.

PMID- 8280657
TI  - Recombinant human interleukin-3 hastens trilineage hematopoietic recovery
      following high-dose (7 g/m2) cyclophosphamide cancer therapy.
AB  - BACKGROUND: Interleukin-3, a recombinant cytokine with multilineage stimulatory
      effect on hematopoietic cells, was administered to 22 previously untreated breast
      cancer patients following high-dose therapy with cyclophosphamide (7 g/m2).
      PATIENTS AND METHODS: The growth factor, administered through continuous
      intravenous infusion at 1 (3 patients), 2.5 (3 patients), 5 (10 patients) and 10
      micrograms/kg/day (6 patients), was well tolerated up to 5 micrograms/kg/day.
      RESULTS: Nausea, vomiting, fever and headache prevented administration of the
      intended dose to all 6 patients in the 10 micrograms/kg/day cohort. At the
      maximal tolerable dose (5 micrograms/kg/day) the growth factor significantly
      accelerated granulocyte, platelet and reticulocyte recovery as compared to
      matched historical controls who received high-dose cyclophosphamide without
      cytokine infusion. Moreover, no platelet transfusions and fewer erythrocyte
      transfusions were required in interleukin 3-treated patients. In contrast to GM
      CSF and G-CSF, interleukin 3 showed no effect on the mobilization of
      hematopoietic progenitor cells in the peripheral blood. CONCLUSIONS: Interleukin
      3 represents a well-tolerated cytokine, clinically useful for accelerating
      trilineage hematopoietic recovery following severely myelotoxic treatments such
      as high-dose cyclophosphamide.

PMID- 8280658
TI  - High dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin's
      disease: long-term follow-up in 128 patients.
AB  - BACKGROUND: There is little long-term follow-up information after autologous
      transplantation for Hodgkin's disease. We evaluated the influence of various
      prognostic factors and examined the outcome in 128 such patients. PATIENTS AND
      METHODS: Patients received high dose cyclophosphamide, carmustine, and etoposide
      followed by autologous hematopoietic rescue. RESULTS: Patients have been observed
      between 50-130 months (median 77 months) following transplantation. Overall
      survival at four years is estimated as 45 percent, and failure-free survival as
      25 percent. The best results were seen in patients with a good performance
      status, who had failed at most one prior chemotherapy regimen. Failure-free
      survival at four years is estimated as 53 percent for this group. Relapses more
      than 24 months after transplantation were seen in 11 patients. Five patients
      developed myelodysplastic syndromes. Three patients became pregnant after the
      transplant. CONCLUSIONS: Prolonged failure-free survival may be observed
      following high dose chemotherapy and autologous hematopoietic rescue in patients
      with Hodgkin's disease. Superior results were seen in patients without extensive
      prior chemotherapy and in those with a good performance status. Late relapses and
      deaths from secondary myelodysplastic syndromes mandate prolonged follow-up after
      autologous transplantation for Hodgkin's disease.

PMID- 8280659
TI  - Epirubicin in patients with advanced or recurrent adenoid cystic carcinoma of the
      head and neck: a phase II study of the EORTC Head and Neck Cancer Cooperative
      Group.
AB  - BACKGROUND: Because of the rarity of salivary gland cancer, little is known about
      the single-agent activity of most anticancer agents in the different histologic
      types of these cancers. PATIENTS AND METHODS: Twenty patients with advanced or
      recurrent adenoid cystic carcinoma of the head and neck were treated with
      epirubicin on a low-dose weekly schedule (30 mg/m2/week) for eight weeks and, in
      instances of no response, a high-dose three-weekly schedule (> or = 90 mg/m2).
      Thirteen patients had locoregional disease (12 recurrences), seven of them also
      had distant metastases and seven had distant metastases only. All had documented
      progressive disease, and 17 were symptomatic. RESULTS: Two objective responses of
      7.5 and 20 months were observed in patients with locally recurrent disease, and
      ten patients showed disease stabilization. The median time to progression was 16
      weeks (range 2-250 weeks) and the median survival 67 weeks (range 13-272+ weeks),
      with three patients still alive more than five years after the initiation of
      chemotherapy. Contrary to the rather modest objective response rate, symptomatic
      improvement occurred more frequently (29.4%) and was evident within 8 weeks of
      treatment. CONCLUSIONS: This type of chemotherapy should be reserved for patients
      with rapidly progressive disease or those with symptomatic disease.

PMID- 8280660
TI  - Phase II study of oral administration of etoposide for patients with well- and
      moderately-differentiated adenocarcinomas of unknown primary site.
AB  - BACKGROUND: The prognosis of patients with well- and moderately-differentiated
      adenocarcinomas of unknown primary is poor, as a consequence of chemotherapy
      resistance. PATIENTS AND METHODS: We performed a phase II study with prolonged
      oral administration of etoposide in 25 chemotherapy-naive patients with well- and
      moderately-differentiated adenocarcinomas of unknown primary site. The treatment
      regimen was 50 mg/m2 for 21 days, every four weeks. RESULTS: Of 24 evaluable
      patients, two achieved partial responses (8%) lasting 15+ and 17 months, 11
      patients had stable disease, and 11 progressed during treatment. The major
      toxicity was myelosuppression. WHO grades 3 or 4 leukocytopenia was seen in six
      patients but confined to the first treatment cycle in five of them. Four of these
      latter five patients already had disease progression after one treatment cycle. A
      primary tumor site was later identified in four patients, three colon carcinomas
      and one carcinoma of the pancreas. CONCLUSION: Etoposide given in this dose and
      schedule has only limited activity in patients with well- or moderately
      differentiated adenocarcinomas of unknown primary site.

PMID- 8280661
TI  - Feasibility study of FEC-chemotherapy with dose-intensive epirubicin as initial
      treatment in high-risk breast cancer.
AB  - BACKGROUND: The prognosis of patients with stage III B breast carcinoma with
      metastasis to the apical axillary lymph nodes is poor despite adequate local
      control achieved by surgery and/or radiation therapy. This study evaluated the
      feasibility of a dose-intensive up-front chemotherapy regimen in this subgroup of
      patients. PATIENTS AND METHODS: A preoperative chemotherapy regimen consisting of
      3 courses of fluorouracil 500 mg/m2, dose-intensive epidoxorubicin 120 mg/m2 and
      cyclophosphamide 500 mg/m2 (DIE-FEC), was administered at 21-day intervals
      without hematopoietic growth factors to 31 patients with apex-positive disease.
      All patients were below 60 years of age and none had had prior chemotherapy or
      radiotherapy. RESULTS: Seven patients achieved clinical complete responses (23%),
      and 21 achieved clinical partial responses (68%); three patients had stable
      disease (10%), one of whom had only ductal carcinoma in situ at histopathologic
      evaluation, which suggested an additional response to therapy. The major toxicity
      was moderate bone marrow suppression with a median WBC nadir of 1650/microliters
      (range 500-4600). Other toxic effects were mild. CONCLUSION: DIE-FEC is well
      tolerated and highly effective as up-front chemotherapy in relatively young
      patients with high-risk breast cancer, with a 90% (CI 74%-98%) clinical objective
      response rate.

PMID- 8280662
TI  - Second-line M-VAC therapy in patients previously treated with the M-VAC regimen
      for metastatic urothelial cancer.

PMID- 8280663
TI  - Euthanasia: less confusion from the professional point of view.

PMID- 8280664
TI  - Antiemetic therapy: the state of the art.

PMID- 8280665
TI  - Description and measurement of anatomical joint motion.
AB  - Recently, three-dimensional measurement of human movement has become practically
      available due to the development of sensor techniques, and the miniaturization
      and cost reduction of computers. As well as accurate and reliable sensors,
      powerful and inexpensive computers are indispensable for processing the large
      quantity of motion data that must be obtained. Measurement and analysis of
      anatomical joint motion would be useful for the evaluation of diseases, outcome
      of surgical operations and effects of rehabilitation, as well as for training in
      sports activities. The present article reviews the mathematical description and
      measurement of anatomical joint motion.

PMID- 8280666
TI  - A method of computing the intersurface distance between opposing teeth.
AB  - Conventional methods of clinically evaluating tooth occlusion, employing
      articulating papers and bite impression materials, do not permit a quantitative
      analysis the occlusion. To overcome this, the shapes of opposing teeth are
      digitized in three-dimensions and intersurface distances are evaluated in detail.
      Computational geometry deals with this as a closest-point problem, i.e. the
      closest points from each surface point must be found by scanning the opposing
      surface. This process is, in most cases, quite time consuming. In order to
      expedite the computations required, we present here an algorithm for this
      determination, whereby the scan area is successively reduced without complicating
      the scanning procedure, thus accelerating the search. The efficiency of this
      algorithm was experimentally proved by comparing its computation time with that
      of the algorithm previously used.

PMID- 8280667
TI  - Potential errors in measuring the phase difference between chest flow and mouth
      flow.
AB  - We have previously reported that the phase difference between chest and mouth
      flows was a useful indicator of obstructive lung disease. In this paper, we
      calculated the effects of (i) airway reactance, (ii) extrathoracic airway shunt
      impedance, (iii) heating and humidification of the inspired air, (iv) abdominal
      gas volume, and (v) respiratory quotient on the measurement of the phase
      difference between chest flow (Vc) and mouth flow (Vm) using computer
      simulations. When the airway impedance was approximated as simple airway
      resistance, the phase difference (theta r) was calculated to be 0.8% less than
      the phase difference (theta s) calculated from the airway impedance (Za),
      including airway inertance and shunt compliance, in the normal lung. theta s
      became larger than theta r when the peripheral resistance increased, but did not
      exceed 5%. The extrathoracic airway shunt impedance effect did not exceed 0.1%,
      regardless of the respiratory frequency, airway impedance or thoracic gas volume.
      The influence of heating and humidification of the inspired air on the phase
      difference was calculated to be within 5%. The effect of abdominal gas was highly
      dependent on the abdominal gas volume and the respiratory pattern, but was
      calculated to be within 5%. The influence of the respiratory quotient was
      calculated to be negligible. As a result, it was concluded that none of the
      factors discussed above are an obstacle to the clinical application of this
      method for the evaluation of pathological changes in obstructive airway
      disorders.

PMID- 8280668
TI  - An investigation of the accuracy in measuring the body center of pressure in a
      standing posture with a force plate.
AB  - It has been reported that accuracy in the measured point of force application
      depends on the position and magnitude of load. The aim of this study is to
      investigate the error in measuring the body center of pressure in a standing
      posture with a force plate and to improve the accuracy by proposing a correction
      algorithm. The measurement of the point of force application with a calibrated
      load demonstrated its co-ordinates, which were scaled down towards the zero co
      ordinate and moved parallel relative to the true co-ordinates. This trend was
      exaggerated with any decrease in magnitude of the load. The root mean square
      (r.m.s.) and maximum of errors at light load of 10 kg were 10 and 18 mm in the X
      axis, and 6 and 12 mm in the Y axis, respectively. The error seems to result from
      such causes as (i) non-linearity of the load cell, (ii) deformation of the top
      plate due to load application and (iii) differences in characteristics among
      individual load cells, including amplifiers. A mathematical representation of the
      measured point of force application accounting for these causes of error has been
      made and an algorithm for estimating the true point at any magnitude of load with
      only one correction equation is proposed. Actual correction of the measured point
      demonstrated an expected improvement in the r.m.s. error to less than 1 mm at any
      magnitude of load greater than 10 kg and the validity of this algorithm was
      confirmed.

PMID- 8280669
TI  - A system for the continuous measurement of ankle joint moment in hemiplegic
      patients wearing ankle-foot orthoses.
AB  - Plastic ankle-foot orthoses (PAFOs) are now commonly used in clinical practice to
      supplement the gait disabilities of hemiplegic patients. However, few
      biomechanical investigation have been performed to analyze the corrective
      functions of PAFOs. In this paper, a measuring system was developed to assess the
      effect of dorsi/plantar flexibility of a PAFO on patient's gait. First, a
      mathematical model of gait with a PAFO was established so that the overall ankle
      joint moment can be separated into the muscle moment and the corrective moment
      generated by a PAFO. An experimental AFO, which simulates PAFOs, was specially
      designed and fabricated to continuously measure the corrective moment of the
      experimental AFO during gait. A device was also developed to continuously measure
      the overall ankle joint moment, so that the muscle moment can be estimated from
      the data obtained by the two devices. The measurement accuracy of the device was
      evaluated using gait data of eight healthy subjects who simulated hemiplegic
      gait. The range of the mean +/- 1 SD of the errors, calculated for the eight
      subjects, fell within +/- 5 Nm, which well compares with the error of commonly
      used comprehensive gait analysis systems.

PMID- 8280670
TI  - Biomedical engineering research programs in Nagoya Institute of Technology.

PMID- 8280671
TI  - Migration of bacteria along synthetic polymeric fibers.
AB  - E. coli, S. epidermidis, and B. distasonis were observed to migrate readily along
      polymer fibers impressed upon the surface of nutrient agar. E. coli was also
      observed to migrate readily along polymer fibers embedded in brain-heart infusion
      agar. Within periods of about 24 h, migration distances of about several
      centimeters were observed. No migration was observed in control experiments
      conducted on or in the same media, but without fibers. Migration speed was
      greatest for E. coli and slowest for B. distasonis. Cell population density was
      found to decrease rapidly with distance from a source culture. Swimming motility
      or natural convection in liquid between fiber and gel appears to be improbable
      based on the expected dimensions of capillary-condensed liquid between fiber and
      gel.

PMID- 8280672
TI  - Preparation and surface properties of PEO-sulfonate grafted polyurethanes for
      enhanced blood compatibility.
AB  - In order to improve the thromboresistance of the commercial polyurethane(PU), its
      surface modification was accomplished by three new different methods and their
      surface characteristics were investigated using ATR-FTIR, ESCA, SEM, and dynamic
      contact angle measurements. Sulfonations using propane sultone were performed
      directly onto PU or onto hydrophobic dodecanediol (DDO) grafted PU or onto
      hydrophilic poly(ethyleneoxide) (PEO) grafted PU. ESCA data coincided well with
      ATR-IR results, as more 0 at. % for PEO grafted PUs and the presence of S for the
      sulfonated PUs were revealed. At SEM observation the surfaces of PU-DDO and PU
      PEO were relatively smooth, whereas all the sulfonated PU surfaces showed
      excellent smoothness and homogeneity. The hydrophilicity of the surfaces was
      considerably increased after PEO grafting or sulfonation. In addition, all the
      sulfonated PU surfaces, particularly PU-PEO-SO3, which has further
      hydrophilicity, exhibited complete wetting behavior due to the negatively charged
      SO3 groups.

PMID- 8280673
TI  - Protein adsorption studies on 'standard' polymeric materials.
AB  - Adsorption of fibrinogen from buffer as a single protein and from plasma to four
      materials has been studied. The two NIH-NHLBI primary reference standards, filler
      free polydimethylsiloxane and low density polyethylene, were used along with
      polyvinylcholoride and cellulose materials supplied by the IUPAC Working Party.
      The materials were examined in both film and tubing form, except for
      polydimethylsiloxane which was studied only in tubing form. Adsorption was
      measured at room temperature using 125I-labelled fibrinogen. The order of
      adsorbed amounts in the single protein experiments was found to be: cellulose <
      PVC < PE = PDMS. Apparent adsorption affinities are in the same order. In plasma,
      all surfaces except cellulose showed maxima in adsorption as a function of plasma
      concentration after 5 min contact. This is indicative of initial adsorption
      followed by displacement of fibrinogen (the Vroman effect). Cellulose showed very
      low adsorption of fibrinogen from plasma. The Vroman maxima were more pronounced
      on the tubing samples than on the films, and, as for the single protein
      experiments, adsorption was found to be less on tubing than on film samples. A
      tentative interpretation of the Vroman effect data suggests that the order of
      procoagulant activity of the materials may be: PDMS = PE < PVC < cellulose.

PMID- 8280674
TI  - Influence of pulsatile flow on the behaviour of human fibroblasts adhered to
      glass.
AB  - In the human body, cells contacting biomaterials surfaces are frequently exposed
      to pulsatile shear stresses, e.g. blood vessel prostheses. Most studies involving
      shear, however, try to achieve a steady, pulse-free shear stress in studying cell
      biomaterial interactions. In this study, human fibroblasts adhering to glass were
      exposed to an applied 0.5 Hz square-wave pulsatile shear, created in a parallel
      plate flow chamber by a computer-driven pump. Cells were also exposed to the
      single lower and higher shear stresses making up the square wave in the presence
      or absence of pressure variations due to the peristaltic roller pump. Results
      indicate that cells exposed to the applied square-wave regime showed a detachment
      rate in between that of the single shear stresses making up the square wave.
      Furthermore, the presence of the pulsations gave rise to elongated cell shapes in
      the direction of flow and the formation of a more extensive filopodial network
      than in the absence of pulsations. This was also true for cells exposed to the
      high shear component in the presence of pressure variations. Cells exposed to the
      high shear component without any pressure variations, however, adapted spherical
      shapes after the onset of flow.

PMID- 8280675
TI  - Towards a synthetic articular cartilage.
AB  - The physical and morphological properties of articular cartilage have been used
      as a model for the preparation of hydrogel based synthetic analogues of this
      complex high water content natural hydrogel. The relatively poor strength and
      stiffness of simple homogeneous hydrogels have been enhanced by semi
      interpenetrating polymer network (semi-IPN) technology to a level which enables
      the mechanical properties of natural cartilage to be approached. Maintenance of
      chondrocytic phenotypes at the implant interface in vitro has been found to
      require careful control of pore size and distribution in the hydrogel matrix. The
      study of synthetic techniques for the fabrication of macroporous semi-IPNs has
      enabled hydrogel semi-IPNs with appropriate pore sizes and mechanical properties
      to be produced. A range of in vitro testing techniques have been developed to
      enable the physico-chemical properties of these materials to be optimised prior
      to animal studies.

PMID- 8280676
TI  - On the structure of electrical double layer of IgG immobilized on polystyrene
      microspheres.
AB  - Latex particles used in the development of immunoassays usually present stability
      problems when the antibody is attached to the surface. This work is an attempt to
      know the potential distribution parameters around these complexes by
      electrokinetic measurements. The conversion of mobility data into zeta-potential
      was carried out by different theoretical approaches developed by Smoluchowski
      (classical equation), O'Brien and White, and Dukhin and Semenikhin. The zeta
      potential calculated with allowance for electrical double layer (e.d.l.)
      polarization was substantially greater than zeta calculated according to the
      classical electrokinetic theory. The greater values of zeta D-S in comparison
      with zeta O-W were readily explained on the basis that in the first theory, the
      contribution to polarization from all ions of the diffuse layer was taken into
      account, whereas O'Brien and White accounted for only the ions of the
      hydrodynamically mobile part of the e.d.l. This is an indication that the
      anomalous surface conductance of latex particles coated by IgG molecules is much
      higher than that of bare latex particles.

PMID- 8280677
TI  - The activation of human plasma prekallikrein as a hemocompatibility test for
      biomaterials. II. Contact activation by EVAL and EVAL-SMA copolymers.
AB  - The activation of human plasma prekallikrein (PKK) to kallikrein (KK), induced by
      the contact of blood with foreign materials, is a useful in vitro
      hemocompatibility test. Kallikrein is easily detected by its reaction with the
      chromogenic substrate H-D-Pro-Phe-Arg-pNA, which releases p-nitroaniline,
      revealed by its absorption at 405 nm. This test, which was already carried out by
      evaluating PKK activation by the 'end-point' method, has been carried out in this
      work by the more accurate 'initial velocity' method, i.e. by evaluating the
      activation from the initial rates of the KK-substrate reaction. The tests were
      carried out on the following materials: borosilicate glass (as a high-activation
      reference material), silicone (as a low-activation reference material), the
      commercial biomaterial Cardiothane 51, three graft copolymers synthesized in our
      laboratory by reacting ethylene-vinyl alcohol copolymer (EVAL) with styrene
      maleic anhydride copolymer (SMA), and EVAL itself. A mathematical treatment based
      on a simple kinetic model has been used for a first-approximation evaluation of
      the PKK-activating power of the materials tested. The quite low activating power
      of the EVAL-SMA copolymers, which are easily processable into water-permeable
      hollow fibers, suggests the possibility of their use in blood dialyzers.

PMID- 8280678
TI  - Melanomas, metastases, and survival.

PMID- 8280679
TI  - Macrophages in the pathobiology of epiretinal membranes: multifunctional cells
      for a multistage process.

PMID- 8280680
TI  - Prognostic factors following enucleation of 111 uveal melanomas.
AB  - Follow up information was retrieved on 111 patients who underwent enucleation for
      uveal melanoma between 1964 and 1987, allowing a minimum postoperative period of
      5 years. Univariate survival analysis was carried out using Kaplan-Meier curves
      and the differences between the curves were analysed with the Mantel-Cox test.
      Multivariate analysis used the Cox proportional hazards model. Univariate
      analysis isolated each of the following as significant prognosticators: largest
      tumour diameter (LTD) (p < 0.002), presence of epithelioid cells (p < 0.03), and
      glaucoma (p < 0.001). A combination of cell type, glaucoma, and LTD (p < 0.0001)
      had strong and independent prognostic significance in multivariate analysis. The
      results of this series are compared with previous studies and the value of cell
      type information and new quantitative parameters is discussed.

PMID- 8280681
TI  - Effects of topical mitomycin C on primary trabeculectomies and combined
      procedures.
AB  - The charts were reviewed of all patients who underwent primary trabeculectomies
      (group 1) or combined procedures (phacoemulsification + intraocular lens
      implantation + trabeculectomy--group 2) and received intraoperative mitomycin C
      (0.4 mg/ml) between 1991 and 1992 at Wills Eye Hospital. A total of 54 eyes of 54
      patients were included: 39 in group 1 and 15 in group 2. Intraocular pressure was
      controlled successfully in 97.4% of eyes in group 1 (mean follow up 6.7 months),
      and in 93.3% in group 2 (mean follow up 6.8 months). Main complications included
      choroidal detachment (n = 15), shallow anterior chamber (n = 9), cataract
      formation (n = 8), and hypotony maculopathy (n = 3). The use of mitomycin C in
      primary trabeculectomies and combined procedures is associated with high success
      rates. However, it may be associated with unacceptable risks of vision
      threatening complications related to excessive filtration.

PMID- 8280682
TI  - Pterygium excision with conjunctival autografting: an effective and safe
      technique.
AB  - The optimum mode of treatment for symptomatic pterygia would combine efficacy (a
      low recurrence rate) with safety (freedom from sight threatening complications),
      and would not affect visual acuity adversely. The efficacy of pterygium excision
      with conjunctival autografting in a sun exposed population in which pterygia are
      prevalent has previously been questioned. A cross sectional review of 93 eyes of
      85 patients was carried out by slit-lamp examination a minimum of 6 months (range
      6-76 months) after pterygium excision and free conjunctival autografting. Case
      notes were reviewed to obtain details of complications and visual acuity changes
      related to surgery. Of six recurrences (6.5%) four of these were asymptomatic
      with minor recurrences. Two patterns of recurrence were identified: cross graft
      recurrence (three cases) and outflanking (three cases). Complications (wound
      dehiscence, three cases; Tenon's granuloma one case; conjunctival cyst, one case)
      were all corrected by minor surgical revision without sequelae. Unaided acuities
      were unchanged or improved 3 months after surgery in 86 cases, with a minor
      diminution (1 Snellen line) in seven cases. This study demonstrates a low
      recurrence rate for a safe technique in an area in which ongoing ultraviolet
      light exposure levels are high and pterygia are prevalent.

PMID- 8280683
TI  - Treatment of band keratopathy by excimer laser phototherapeutic keratectomy:
      surgical techniques and long term follow up.
AB  - A series of 122 eyes with band keratopathy was treated by excimer laser
      phototherapeutic keratectomy (PTK), with a mean follow up of over 12.3 months
      (range 3 to 60 months). A single photoablation zone was used to remove the
      opacity over the visual axis in smooth surfaced band deposition. In eyes with
      reduced vision, an improvement was reported in 88% and in a series of 66 eyes
      mean Snellen visual acuity increased significantly (p < 0.05, t = 2.27). A
      reduction in glare was reported in 88% and in a series of 17 patients, visual
      contrast sensitivity (p < 0.01) and measurements of disability glare (p < 0.01)
      improved postoperatively. The mean hyperopic shift in 32 eyes at 6 months was 1.4
      D (range 0-4.25 D). Multiple overlapping ablation zones, with mechanical
      debulking of large calcium plaques, were used to smooth the irregular corneal
      surface in eyes with rough bands. Ocular discomfort was improved in 95%. Band
      keratopathy recurred in nine eyes (8%) within 2 to 30 months (mean 12 months) of
      surgery, with silicone oil responsible in five eyes. Reablation was necessary in
      three eyes and performed successfully in all cases. Excimer laser PTK is a safe
      and effective outpatient treatment for band keratopathy.

PMID- 8280684
TI  - Contrast sensitivity function in Graves' ophthalmopathy and dysthyroid optic
      neuropathy.
AB  - Contrast sensitivity function was measured by a computer automated method on 38
      eyes with dysthyroid optic neuropathy and 34 eyes with Graves' ophthalmopathy
      only. The results were compared with 74 healthy control eyes. Disturbances of
      contrast sensitivity functions were found in both groups when compared with
      controls. The eyes affected with dysthyroid optic neuropathy showed pronounced
      loss of contrast sensitivity in the low frequency range, which facilitates
      differentiation between the two groups.

PMID- 8280685
TI  - A comparison of the efficacy and duration of action of topically applied
      proxymetacaine using a novel ophthalmic delivery system versus eye drops in
      healthy young volunteers.
AB  - A novel ophthalmic drug delivery system (NODS) has been developed to give precise
      and controlled delivery of a drug to the eye. The drug is incorporated into a
      polyvinyl alcohol flag attached to a carrier. When applied to the eye the flag
      detaches and gradually dissolves, releasing the drug. We investigated corneal
      anaesthesia produced by different concentrations of proxymetacaine NODS, and
      conventional eye drops. Subjects consisted of 28 normal males (mean age 25.3 (SD
      3.9) years). Corneal touch sensitivity was measured with a biomicroscope mounted
      Cochet-Bonnet aesthesiometer. Each subject attended for two visits separated by 7
      days. On each visit each eye randomly received one of four proxymetacaine
      preparations: 44 micrograms, 74 micrograms, 124 micrograms NODS, or 35
      microliters of 0.5% proxymetacaine drops (175 micrograms). Corneal touch
      sensitivity was measured before, and at 1, 2, 5, 10, 15, 20, 30, 45, and 60
      minutes following instillation. Complete anesthesia was achieved in the majority
      of subjects within 1 minute of instillation. The lowest NODS dose (44 micrograms)
      produced longer lasting anaesthesia than the 35 microliters drop (175 micrograms)
      (p < 0.05). Higher NODS doses produced a correspondingly greater increase in the
      duration of anaesthesia. The greater bioavailability achieved by this vehicle
      allows much lower drug concentrations to be used, reducing the likelihood of
      systemic adverse reactions.

PMID- 8280687
TI  - The effect of pilocarpine on the glaucomatous visual field.
AB  - Patients with chronic open angle glaucoma are traditionally managed by medical
      therapy during the early stages of the disease. Pilocarpine is a well established
      topical agent, but suffers troublesome sequelae, the most apparent of which is
      pupillary constriction. This study assesses the effect of miosis (produced by one
      drop of 2% pilocarpine) on the static threshold perimetry of 20 subjects with
      chronic open angle glaucoma and documented visual field loss, using the 30-2
      program of the Humphrey field analyser. Following miosis, the Statpac mean defect
      deteriorated by an average of -1.49 dB compared with baseline (p = 0.004). This
      dB deterioration is twice that reported in studies on younger normal subjects
      following miosis. The decrease in mean defect showed a positive correlation with
      the degree of pupillary constriction, the correlation being greater in those eyes
      with a miosed pupil diameter of 2 mm or less. There was no significant decrease
      in the other Statpac global indices following miosis. A parallel study using the
      fellow eye of the same glaucoma patients showed a high degree of intertest
      variability, but no significant learning or fatigue effect. We conclude that
      pilocarpine-induced miosis causes a significant deterioration in visual field in
      a population of patients with chronic open angle glaucoma: this factor should be
      considered when choosing therapy for glaucoma particularly in cases where field
      loss approaches the permitted legal minimum for driving.

PMID- 8280686
TI  - Impairment of colour contrast sensitivity and neuroretinal dysfunction in
      patients with symptomatic HIV infection or AIDS.
AB  - Ophthalmic and neurological complications are frequent findings in patients with
      AIDS. Little is known about neuroretinal dysfunction in patients with HIV
      infection. The purpose of this study was to measure and evaluate colour vision in
      patients with HIV infection or AIDS. Colour contrast sensitivity tests were
      performed on 75 patients (150 eyes) in different stages of HIV infection. A
      highly sensitive computer graphics system was used to measure tritan, deutan, and
      protan colour contrast thresholds. Patients were classified into three clinical
      groups: (a) asymptomatic HIV infection, (b) lymphadenopathy syndrome or AIDS
      related complex, and (c) AIDS. Overall, tritan (p < 0.0001), deutan (p = 0.003),
      and protan (p = 0.009) colour contrast sensitivities were significantly impaired
      in patients with HIV infection compared with normal controls. Colour thresholds
      in patients with asymptomatic HIV infection (mean tritan threshold: 4.33; deutan:
      4.41; protan: 3.97) were not impaired compared with normal controls. Colour
      vision was slightly impaired in patients with lymphadenopathy syndrome or AIDS
      related complex (tritan: 6.25 (p < 0.0001); deutan: 4.99 (p = 0.02); protan: 4.45
      (p = 0.05)). In patients with AIDS the impairment was even more marked (tritan:
      7.66 (p < 0.0001); deutan: 5.15 (p < 0.0009); protan: 4.63 (p = 0.004)). Analysis
      of covariance controlling for age demonstrated a close association between
      impairment of tritan colour contrast sensitivity and progression of HIV disease
      (p < 0.0001). Following Kollner's rule, our study suggests that neuroretinal
      dysfunction occurs in patients with symptomatic HIV infection or AIDS. This is
      emphasised by the finding that the relative impairment in tritan vision compared
      with deutan/protan vision might reflect the difference in the number of cones or
      receptive fields. Measurement of tritan colour contrast sensitivity appears to be
      an appropriate and easily applicable method to detect early neuroretinal
      dysfunction in patients with HIV disease.

PMID- 8280689
TI  - After Helmholtz.

PMID- 8280688
TI  - Visual field loss with capillary non-perfusion in preproliferative and early
      proliferative diabetic retinopathy.
AB  - Thirty two eyes of 19 patients with capillary non-perfusion from preproliferative
      and early proliferative diabetic retinopathy underwent visual field testing on
      the 30-2 program of the Humphrey visual field analyser. The mean defect (MD) p
      value was < 5% in 30 (94%) eyes and the corrected pattern standard deviation
      (CPSD) was < 10% in 31 (97%) eyes. Areas of capillary non-perfusion demonstrated
      by fundal fluorescein angiography were closely associated with areas of reduced
      retinal sensitivity in these 31 eyes. More severe visual field defects were
      present in non-insulin dependent diabetics and in older patients. MD and CPSD p
      values of less than 0.5% and 1% respectively were found to be associated with non
      insulin dependent diabetes (p < 0.05 and p < 0.01 respectively) and with the
      older age group (p < 0.05). There was no correlation between severity of field
      defects with hypertension and degree of retinopathy.

PMID- 8280690
TI  - Macrophages in proliferative vitreoretinopathy and proliferative diabetic
      retinopathy: differentiation of subpopulations.
AB  - Macrophages have long been known to play a major role in the pathogenesis of
      proliferative vitreoretinal disorders. Using the monoclonal antibodies EBM11 (pan
      macrophage), 27E10 (early inflammatory stage marker), and RM3/1 (healing phase
      marker), different subpopulations of macrophages were differentiated in
      surgically removed membranes from patients with macular pucker (n = 6),
      proliferative vitreoretinopathy (PVR) following rhegmatogenous retinal detachment
      (n = 11), traumatic PVR (n = 19), and proliferative diabetic retinopathy (PDR) (n
      = 11). Macrophages were predominantly found in traumatic PVR and PDR. Some
      healing phase (RM3/1) macrophages were detected in all disease entities.
      Inflammatory stage macrophages (positive staining for 27E10) could not be
      detected in PVR following rhegmatogenous retinal detachment and idiopathic
      macular pucker. In traumatic PVR inflammatory stage macrophages were associated
      with a short history of disease whereas in PDR all types of macrophages could be
      detected regardless of clinical history and duration of the disease.

PMID- 8280692
TI  - Iris cyst after traumatic implantation of an eyelash into the anterior chamber.

PMID- 8280691
TI  - Pterygium as an early indicator of ultraviolet insolation: a hypothesis.

PMID- 8280693
TI  - Recurrent episcleritis associated with adult T cell leukaemia.

PMID- 8280694
TI  - Development of retinal vascular leakage and cystoid macular oedema secondary to
      central serous chorioretinopathy.

PMID- 8280695
TI  - Familial clustering of human T lymphotropic virus type 1 uveitis.

PMID- 8280696
TI  - An atypical Leber's hereditary optic neuropathy with the 11778 mutation.

PMID- 8280697
TI  - A cranial nerve palsy associated with Mycoplasma pneumoniae infection. Polymerase
      chain reaction evidence against an infectious mechanism.

PMID- 8280698
TI  - Topical chemotherapy for conjunctival melanoma.

PMID- 8280699
TI  - Tono-Pen tonometry.

PMID- 8280700
TI  - Comparison between methods of tonometry: time for a change of approach.

PMID- 8280701
TI  - Genes coding for tumor antigens recognized by human cytolytic T lymphocytes.
AB  - In order to define the antigens recognized by cytolytic T lymphocytes (CTLs) on
      autologous tumors, we derived tumor-specific CTL clones from autologous mixed
      lymphocyte tumor cell cultures. The gene coding for a tumor rejection antigen
      expressed on a melanoma was isolated by transfecting genomic DNA of the tumor
      into an antigen-loss variant of the melanoma. Transfectants were identified on
      the basis of their ability to stimulate tumor necrosis factor release by the CTL
      clone. The gene that transferred the expression of the antigen was named MAGE-1.
      It is a new gene, silent in normal tissues with the exception of testis, but
      expressed in several types of tumors. The antigen recognized by the CTL clone is
      a nonapeptide derived from the protein encoded by gene MAGE-1, and presented by
      the HLA class I molecule HLA-A1. Using two other antimelanoma CTL clones, we
      identified the tyrosinase gene as coding for an antigen presented by HLA-A2 on
      this type of tumors. The identification of these tumor rejection antigens open
      new possibilities for the specific immunotherapy of cancer.

PMID- 8280702
TI  - Vaccinia virus MUC1 immunization of mice: immune response and protection against
      the growth of murine tumors bearing the MUC1 antigen.
AB  - MUC1 is a mucin found on the apical surfaces of some normal mammalian mucin
      secreting cells. It is characterized by heavy glycosylation and a 20-amino-acid
      tandem repeat segment. In most cases of human breast adenocarcinoma, this antigen
      is overexpressed. Moreover, abnormal glycosylation exposes a novel peptide
      epitope within the tandem repeat, such that antibodies to this epitope can
      distinguish normal from malignant adenocarcinomatous breast tissue. We have
      constructed a vaccinia virus (VV) that carries the cDNA for the MUC1 antigen.
      Murine and human cells infected with this virus express the MUC1 molecule, with
      three to four tandem repeats per molecule and with the tumor-associated epitopes
      exposed. Mice immunized with this virus produce antibodies that recognize MUC1
      outside the tandem repeat, within the tandem repeat, and within the tumor
      associated protein core epitope. Tumorigenic P815 (DBA) and 3T3 (BALB/c) cells
      have been transfected with MUC1. Thirty percent of DBA mice immunized with VV
      MUC1 are protected from growth of P815-MUC1 tumors when implanted with 10(5)
      cells. Immunized BALB/c mice show a late development of transfected 3T3 tumor
      cells. Immunized mice show a moderate MUC1-specific IgG titer, but it cannot be
      correlated with subsequent tumor rejection. No evidence for a MUC1-specific
      cytotoxic T lymphocyte response has been found after immunization with VV-MUC1.

PMID- 8280703
TI  - Comparison of the H-2Kk- and H-2Kkm1-restricted peptide motifs.
AB  - Self-peptide pools eluted from purified H-2Kk or H-2Kkm1 molecules were
      sequenced. The majority of self-peptides associated with H-2Kk molecules were
      found to be octamers with two anchor positions. Position 2 is invariantly
      occupied with Glu, and the C-terminal residue at position 8 is almost always Ile.
      Comparison of this motif with synthetic peptides known to contain viral or
      parasite T-cell epitopes could be well aligned with this motif, except that the C
      terminal Ile residue frequently appears to be at position 9 of the aligned
      sequences, instead of 8. Self-peptides eluted from mutant H-2Kkm1 molecules also
      appear to be mostly octamers with the same Ile residues at position 8 as with Kk.
      Position 2 is still dominantly occupied by Glu; in contrast to the Kk motif,
      however, Gln, Gly, and Pro are also allowed. Other differences between the two
      motifs indicate that a certain number of peptides presented by one of the
      molecules are not presented by the other.

PMID- 8280704
TI  - Report on the Keystone symposium: cellular immunity and the immunotherapy of
      cancer II.

PMID- 8280705
TI  - T-cell recognition of human melanoma antigens.
AB  - The adoptive transfer of tumor-infiltrating lymphocytes (TILs) with interleukin-2
      (IL-2) has antitumor activity in some patients with metastatic melanoma. We have
      analyzed molecular mechanisms of TIL recognition of human melanoma. Some cultured
      TILs specifically lysed autologous and some allogeneic melanomas sharing a
      variety of class I major histocompatibility complex (MHC) molecules. HLA-A2
      restricted melanoma-specific TILs lysed many HLA-A2+ melanoma cell lines from
      different patients but failed to lyse HLA-A2- melanoma and HLA-A2+ nonmelanoma
      cell lines. However, these TILs were capable of lysing many naturally HLA-A2-
      melanomas after introduction of the HLA-A2.1 gene by vaccinia virus. These
      results indicate that shared melanoma antigens (Ag) are expressed in melanomas
      regardless of their human leukocyte antigen types. In order to identify these
      shared melanoma Ags, we have tested some known proteins expressed in melanoma.
      Expression of tyrosinase or HMB45 Ag correlated with lysis of TILs. We are also
      attempting to isolate antigenic peptides by high performance liquid
      chromatography separation and genes encoding melanoma Ag by cDNA expression
      cloning. The T-cell component of the antimelanoma response was also analyzed by
      determining the genetic structure of the T-cell receptor (TCR) used by melanoma
      TILs. However, we did not observe common TCR variable region usage by different
      melanoma TILs. We could establish melanoma cell clones and lines resistant to TIL
      lysis due to the absence of or defects in the expression of Ag, MHC, or beta 2
      microglobulin molecules. These data indicate multiple mechanisms for melanoma
      escape from T-cell immunosurveillance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280706
TI  - Cytokine-induced tumor immunogenicity: from exogenous cytokines to gene therapy.
AB  - The local presence of cytokines can drastically alter tumor host immune relations
      and activate a nonspecific reaction that in some cases leads to induction of
      specific responses to otherwise nonimmunogenic tumors. The employment of
      cytokines in the creation of new antitumor vaccines is thus a tempting prospect.
      Analogous effects have been obtained with cytokines inoculated locally and
      cytokines released from tumor cells engineered to produce them. An account is
      given of some mechanisms whereby this cytokine-induced reaction results in
      increased tumor immunogenicity. However, the real value of this potential form of
      vaccine in inducing the regression of incipient or established tumors remains to
      be established.

PMID- 8280707
TI  - Recombinant vaccinia interleukin-2-infected tumor cell vaccines in immunotherapy
      of murine colon adenocarcinoma.
AB  - A recombinant vaccinia virus (vCF13) containing and expressing the gene for human
      interleukin (IL)-2(vCF13) was compared to a recombinant vaccinia transfection
      control strain containing the LacZ gene at the same insertion site (vTFCLZ-1) for
      their ability to augment the immunogenicity of murine colon adenocarcinoma cell
      lines CT26 and CA51 in Balb/c mice. Both recombinant vaccinia strains abolished
      tumorigenicity of 10(5) CT26 or CA51 tumor cells. vCF13-infected tumor cells that
      secreted human IL-2 as measured by both CTLL-2 and enzyme-linked immunosorbent
      assays induced delay in tumorigenesis when administered in two weekly
      subcutaneous injections 1 week prior to challenge with 10(5) uninfected tumor
      cells. Although three of five vCF13-CT26 immunized mice developed tumors by day
      14 after challenge, intralesional injection of these tumors with vCF13 induced
      rapid regression, whereas all five tumors that developed in vTFCLZ-1 immunized
      mice showed no response to intralesional vTFCLZ-1. These preliminary results
      provide support for the potential utility of recombinant vaccinia/IL-2 in tumor
      immunotherapy.

PMID- 8280708
TI  - A genetic approach to idiotypic vaccination.
AB  - Treatment of cancer with vaccines is an attractive prospect, but few tumours
      express suitable target antigens. With B-cell lymphomas, the idiotypic
      immunoglobulin (Ig) of the malignant B-cell should provide a suitable target but
      this requires a vaccine to be created for each patient. We propose a strategy for
      making such vaccines: first to clone the V genes of the idiotypic Ig, and second
      to inject the patient with the cloned DNA (genetic immunisation) in order to
      elicit an immune response against the encoded Ig. We have previously shown that
      the V genes of the idiotypic Ig can be identified from human lymph node biopsies
      by polymerase chain reaction amplification, cloning, and sequencing. In this
      report, we show that anti-idiotypic antibodies can be elicited by direct
      injection of an expression vector that encodes the V genes of murine antibodies
      (the V genes of B1.8, a murine hybridoma or of BCL1, a murine lymphoma line).
      This finding suggests a simple approach to the preparation of idiotypic vaccines
      for patients with B-cell lymphoma, which also circumvents the need for adjuvants.

PMID- 8280709
TI  - In vivo antitumor efficacy of tumor-draining lymph node cells activated with
      nonspecific T-cell reagents.
AB  - Progressive growth of immunogenic murine tumors elicits a tumor-specific but
      functionally deficient T-cell immune response in the draining lymph nodes. These
      T cells, referred to as "pre-effector" cells could be induced in vitro to
      differentiate into mature immune effector cells, capable of mediating the
      regression of established metastases. Initially, tumor cells were used to
      stimulate the in vitro maturation of pre-effector cells. Alternatively, we found
      that pre-effector cells could be activated by sequential stimulation with anti
      CD3 and interleukin-2 in the absence of tumor cells. In adoptive immunotherapy,
      these activated cells mediated therapeutic effects that were exquisitely specific
      to the tumor that triggered the pre-effector cell response in vivo. Since the
      anti-CD3 interaction with T cells is polyclonal, the activated lymph node cell
      population must also contain a significant number of T cells that do not have
      tumor specificity. In an attempt to selectively activate tumor-sensitized pre
      effector cells, we recently utilized superantigenic bacterial toxins as T-cell
      stimuli for effector cell generation. Superantigens combine with major
      histocompatibility class II molecules to form the ligands that stimulate T cells
      bearing distinct T-cell receptor V beta elements. Lymph node cells draining the
      MCA 205 sarcoma stimulated with staphylococcal enterotoxins A (SEA), B (SEB), or
      C2 (SEC2) resulted in selective expansions of V beta 3 and 11, V beta 3 and 8, or
      V beta 8.2 T cells, respectively. Adoptive immunotherapy experiments revealed
      that SEB- and SEC2-, but not SEA- stimulated cells, mediated tumor-specific
      eradication of pulmonary metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280710
TI  - Liposome-encapsulated MTP-PE: a novel biologic agent for cancer therapy.
AB  - Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), a
      new biologic response modifier, was designed to target the immunomodulator to
      monocytes and macrophages. Human monocytes/macrophages phagocytize L-MTP-PE, with
      subsequent upregulation of interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, tumor
      necrosis factor (TNF)-alpha, and monocyte chemotactic and activating factor genes
      and with the production and secretion of these cytokines in vitro. L-MTP-PE
      activated macrophages kill tumor but not normal cells in vitro. Following i.v.
      infusion of L-MTP-PE into cancer patients, its uptake was demonstrated in liver,
      spleen, lung, and in and around metastases to lung. We also investigated whether
      L-MTP-PE therapy administered in a neoadjuvant setting could improve the disease
      free interval in relapsed osteosarcoma patients with lung metastasis. Patients
      received either a 12- or 24-week course of L-MTP-PE after surgical removal of all
      metastases. Following L-MTP-PE infusion, induction of circulating TNF-alpha, IL
      6, neopterin, and C-reactive protein was demonstrated. Disease-free intervals
      were calculated from the day of surgery to the day of relapse in each group and
      were compared with the disease-free interval for a historical control group.
      Those patients receiving 24 weeks of L-MTP-PE showed a significant (p < 0.03)
      prolongation in time to relapse. These data indicate that L-MTP-PE is an active
      agent against osteosarcoma and warrants further investigation in an adjuvant
      setting.

PMID- 8280711
TI  - Interleukin-3 inhibits the generation of nonspecific killers by interleukin-2.
AB  - Interleukin (IL)-3 has effects on a wide variety of cell types, including
      immature cells of the immune system, as well as mature cells such as
      granulocytes. We have investigated the effects of IL-3 on generation of cytolytic
      cells that can kill tumor cells. Previously, we have shown that IL-3 can enhance
      the development of cytolytic T cells (CTL) reactive with the line 1 tumor in a
      CD4-dependent manner. It is of interest that we found the development of CTL in
      response to IL-3 was not accompanied by increased development of nonspecific
      killer cells. This was in contrast to IL-2, which enhanced development of both
      CTL and nonspecific cells. To determine if IL-3 could inhibit the development of
      nonspecific killers, we added IL-3 to cultures of fresh spleen cells stimulated
      with high levels of IL-2. In this assay, IL-3 showed very potent inhibitory
      activity against the generation of nonspecific killers. To determine if IL-3
      could inhibit the IL-2-driven generation of non-specific killers in vivo, we
      injected a mixture of IL-2- and IL-3-producing line 1 cells. Each cytokine
      producing transfectant was also injected alone. The cytotoxicity of tumor
      infiltrating lymphocytes (TIL) from these tumors confirmed that the presence of
      IL-3 inhibits the generation of nonspecific killer cells in vivo.

PMID- 8280712
TI  - Generation of donor-derived antileukemic cytotoxic T-lymphocyte responses for
      treatment of relapsed leukemia after allogeneic HLA-identical bone marrow
      transplantation.
AB  - Allogeneic bone marrow transplantation (BMT) has been associated with an
      antileukemic effect, the graft-versus-leukemia (GVL) reactivity. Since T-cell
      depletion of the bone marrow graft performed to reduce the incidence and severity
      of graft-versus-host disease (GVHD) after BMT has been associated with an
      increase risk of relapse, the GVL reactivity has been attributed to the T
      lymphocytes from the graft. Previously, we demonstrated that leukemia-reactive
      cytotoxic T-lymphocyte (CTL) lines and clones could be generated from the
      peripheral blood of HLA-genotypically identical siblings of patients with
      leukemia by stimulation of the donor cells with irradiated leukemic cells from
      the patients. HLA class I as well as class II restricted CTL clones could be
      generated that recognized the leukemic cells. Some clones recognized the leukemic
      cells from the patient, but not the interleukin (IL)-2-stimulated lymphocytes
      from the same individual. To explore the possibility of clinically using donor
      derived CTL lines directed against the leukemic cells from patients who relapsed
      after allogeneic BMT, a pilot study was performed using eight donor-recipient
      combinations. In seven of eight combinations donor-derived CTL lines could be
      generated that showed specific lysis of the leukemic cells from the patient. In
      five of these cases, the CTL lines showed reactivity with the leukemic cells, but
      not with the IL-2-stimulated lymphocytes from the same individual. In two cases,
      the CTL lines were cytotoxic for the IL-2-stimulated lymphoblasts as well as the
      leukemic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280713
TI  - Cytokine gene transfer as a therapeutic strategy.
AB  - Cytokine gene therapy for cancer could involve either the direct delivery of
      cytokine genes to established tumours to stimulate their rejection or the
      injection of cytokine-secreting tumour cells to stimulate an immune response that
      could reduce metastatic disease. To assess the feasibility of the first approach,
      we have compared the ability of different cytokine-secreting tumour cells to
      induce the rejection of admixed, unmodified cells. While interleukin (IL)-2- or
      interleukin-4-secreting tumour cells were ineffective, interferon-gamma (IFN
      gamma)-secreting cells could induce rejection of 10% admixed, unmodified cells.
      Because direct gene delivery to tumours is unlikely to be 100% efficient, these
      data suggest that IFN-gamma may be the most suitable of these cytokines for this
      approach. However, we have demonstrated that injection of IL-2-secreting tumour
      cells, following primary tumour excision, can prevent the development of
      metastases and prolong survival of rats. This suggests that IL-2-secreting tumour
      cells can be effective in the treatment of metastatic disease.

PMID- 8280714
TI  - Transfer and expression of the human interleukin-4 gene in carcinoma and stromal
      cell lines derived from lung cancer patients.
AB  - Introduction of the interleukin-4 (IL-4) gene into cells derived from human tumor
      tissue provides a means for generating a specific tumor vaccine. Such a vaccine
      could be produced by either transducing tumor-derived stromal cells with the IL-4
      vector and coinjecting tumor cells, or by transducing the tumor cells themselves.
      We have developed a protocol for culturing cells from non-small cell lung tumors
      and routinely produce tumor cultures from 25% of tumors, and stromal cultures
      from > 80% of specimens. Several of these cultures were transduced with the
      incompetent retroviral vector G1NaSvi4.25, which encodes the human IL-4 cDNA and
      the G418-resistance gene. Infection of cells by viral titers of 2-5 x 10(4)
      plaque-forming units/ml, and a multiplicity of infection of 0.1:1 to 1:1 yielded
      transfer efficiencies of 3.3-32.0 transfectants per 10(4) cells in six of eight
      attempts. Following selection with the neomycin analog G418, IL-4-producing cells
      were isolated. IL-4 titers ranged from 142 to 593 U/ml/10(6) in a 24-h
      collection. Successful transfer of the IL-4 gene was demonstrated by polymerase
      chain reaction amplification of cDNA derived from reverse-transcribed total RNA,
      by immunohistochemistry, and by enzyme-linked immunosorbent assay. The IL-4
      producing cells were shown to stimulate the proliferation of autologous
      peripheral blood lymphocytes in one individual by 7.5-fold over control and by
      4.1-fold over non-IL-4 producing tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280715
TI  - Growth and autologous tumor lysis by tumor-infiltrating lymphocytes from
      metastatic melanoma expanded in interleukin-2 or interleukin-2 plus interleukin
      4.
AB  - Optimal conditions for expanding tumor-infiltrating lymphocytes (TILs)
      specifically cytotoxic for autologous melanoma for clinical use have not yet been
      identified. In several small studies, interleukin (IL)-4 was reported to promote
      the growth of such TILs in IL-2. Given the potential implications for TIL
      therapy, we attempted to confirm these findings in a larger study. Baseline data
      were first obtained on the proliferation, immunophenotype, and cytotoxic
      reactivity to autologous melanoma of TILs cultured in IL-2 alone. Similar studies
      were performed with TIL cultured concurrently in either IL-2 alone or in a
      combination of IL-2 and IL-4. TILs were obtained by excisional biopsy of tumors
      from 52 patients with metastatic malignant melanoma; TILs from 38 patients were
      expanded in IL-2 (1,000 U/ml). TILs from 19 biopsies were maximally expanded 6-
      to 24,000-fold (median, 300-fold) over 4-10 weeks. Expansion did not correlate
      with the weight of, or number of lymphocytes in, the biopsy specimen, or the site
      of the biopsy (lymph node vs. subcutaneous metastases). During weeks 5-8, TILs
      from 19 of 25 biopsy specimens lysed autologous melanoma with little or no lysis
      of allogeneic melanoma. Lysis of autologous tumor was blocked by antibody to
      class I antigens. Twenty-four TIL specimens were cultured concurrently in IL-2
      alone and in IL-2 plus IL-4 and tested for growth and for lysis of autologous and
      allogeneic melanomas.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280716
TI  - Activation of multiple effector mechanisms to enhance tumor immunotherapy.
AB  - Recent technical advances have enabled the generation of clinical reagents for
      immunotherapy. Currently, treatment protocols combining both interleukin-2 (IL-2)
      and tumor-specific monoclonal antibody are underway at the University of
      Wisconsin Comprehensive Cancer Center and elsewhere. These approaches are based
      on the hypothesis that IL-2-activated lymphocytes will use tumor-reactive
      antibody to more selectively and effectively destroy tumor in vivo. Just as IL-2
      can activate lymphocytes to destroy antibody-coated tumor cells, other agents can
      activate neutrophils and monocytes to destroy antibody-treated tumor cells. We
      are investigating, in laboratory and clinic, approaches aimed at eventually using
      combinations of distinct antibody-based tumor recognition mechanisms in patients
      whose monocytes, neutrophils, and lymphocytes have been simultaneously activated
      with multiple biologic agents.

PMID- 8280717
TI  - Expansion of tumor-infiltrating lymphocytes from human tumors using the T-cell
      growth factors interleukin-2 and interleukin-4.
AB  - We examined the role of two T cell-growth factors, interleukin (IL)-2 and IL-4,
      in expansion of tumor-infiltrating lymphocytes (TILs) from human tumors. In
      sarcoma, IL-4 (1,000 U/ml) with IL-2 (10 or 1,000 U/ml) grew TILs better than did
      IL-2 alone in six of 10 cases during 6 weeks of culture. IL-4 decreased the
      relative number of CD56+ cells, which correlated with a decrease in cytolysis
      against Daudi in six of 10 cases. The addition of IL-4 with 1,000 U of IL-2
      maintained or increased cytolysis against autologous sarcoma, while decreasing
      nonspecific cytolysis against Daudi or allogeneic sarcoma in three of eight
      cases. IL-4 decreased cytolysis against both autologous sarcoma and Daudi in four
      of 10 cases, suggesting nonspecific activity in these instances. In renal cell
      cancer (RCC), IL-4 with IL-2 (10 or 1,000 U/ml) augmented TIL growth in six of
      eight cases, especially during the first 2-3 weeks of culture. IL-4 with 10 U of
      IL-2 increased cytolysis against both autologous RCC and Daudi in six of eight
      cases, suggesting possible prior cell activation. In contrast, IL-4 addition with
      1,000 U of IL-2 maintained or increased cytolysis against autologous RCC, while
      decreasing cytolysis against Daudi or allogeneic RCC in four of eight cases. In
      cases of bladder and of prostate cancer, IL-4 with 1,000 U of IL-2 grew TILs
      slightly better in five of seven cases for the first 2-3 weeks. Bladder TILs
      grown with IL-2 and/or IL-4 were CD+ T cell predominant (three of five) and
      rarely lytic for autologous tumor. In colon cancer and hepatoma, TILs grown with
      IL-2 and/or IL-4 were nonlytic for the autologous tumor. IL-4 in conjunction with
      IL-2 could therefore augment growth of some TILs especially for the first 2-3
      weeks from various human tumors.

PMID- 8280718
TI  - Possible myocardial toxicity associated with interleukin-4 therapy.
AB  - Interleukin (IL)-4 is a cytokine produced by T lymphocytes, which may play a role
      in allergic inflammatory processes through its stimulatory effects on
      immunoglobulin E production and mast cells. In this report, we describe a patient
      with metastatic melanoma involving the heart who had biopsy-proven myocarditis
      after treatment with high-dose IL-4. Because of the uncharacteristic predominance
      of polymorphonuclear and mast cells in the inflammatory infiltrate of this
      patient's myocardium, we postulate a unique mechanism of IL-4-associated
      myocarditis. Three other patients treated with IL-4 had less well-defined cardiac
      abnormalities, suggesting that patients receiving IL-4 may be at risk for cardiac
      toxicity. Additional studies will be necessary to confirm such an association.

PMID- 8280719
TI  - Heat shock protein vaccines against cancer.
AB  - Vaccination of mice with heat shock proteins (HSPs) derived from a tumor makes
      the mice resistant to the tumor from which the HSP was obtained. This phenomenon
      has been demonstrated with three HSPs--gp96, hsp90, and hsp70. Vaccination with
      HSPs also elicits antigen-specific cytotoxic T lymphocytes (CTLs). The specific
      immunogenicity of HSPs derives apparently, not from the HSPs per se, but from the
      peptides bound to them. These observations provide the basis for a new generation
      of vaccines against cancer. The HSP-based cancer vaccines circumvent two of the
      most intractable hurdles to cancer immunotherapy. One of them is the possibility
      that human cancers, like cancers of experimental animals, are antigenically
      distinct. The prospect of identification of immunogenic antigens of individual
      cancers from patients is daunting to the extent of being impractical. The
      observation that HSPs chaperone antigenic peptides of the cells from which they
      are derived circumvents this extraordinary hurdle. Second, most current
      approaches to cancer immunotherapy focus on determining the CTL-recognized
      epitopes of cancer cell lines. This approach requires the availability of cell
      lines and CTLs against cancers. These reagents are unavailable for an
      overwhelming proportion of human cancers. In contrast, the HSP-based vaccines do
      not depend on the availability of cell lines or CTLs nor do they require
      definition of the antigenic epitopes of cancer cells. These advantages, among
      others, make HSPs attractive and novel immunogens against cancer.

PMID- 8280720
TI  - Recombinant inbred strains in hypertension research.
AB  - It was recognized that recombinant inbred strains are a very powerful system for
      the study of the genetics of hypertension, linkage analysis and gene mapping.
      Such set of recombinant inbred strains has been developed in the cooperation of
      Prof V. Kren and Dr. M. Pravenec in Prague. These recombinant inbred strains were
      used to search for the genes of spontaneous hypertension and to test the
      phenotypic differences. It was found that 1) the major histocompatibility complex
      of the rats showed a significant association with blood pressure, 2) the
      restriction fragment length polymorphism in kallikrein gene family as well as
      renin gene cosegregated with blood pressure, 3) Na+ leak in red blood cells
      cosegregated with blood pressure, 4) the relative heart and kidney weights are
      not closely related to mean arterial pressure and 5) the platelet aggregation and
      blood pressure are independent traits. The results indicate the usefulness of
      recombinant inbred strains in the analysis of the relationship between phenotype
      and genotype.

PMID- 8280721
TI  - Protein profiling of human atrial and ventricular musculature: the effect of
      normoxaemia and hypoxaemia in congenital heart diseases.
AB  - Samples of myocardial tissue were obtained during surgical intervention from
      children operated for different types of congenital heart disease (tetralogy of
      Fallot, ventricular and atrial septal defect). Sarcoplasmic, contractile and
      collagenous proteins were isolated by stepwise extraction from the both right
      ventricular and atrial musculature. It has been found that: a) the concentration
      of contractile proteins is significantly higher in the ventricles, b) the
      concentration of collagenous proteins is significantly higher in the atrium, c)
      the concentration of sarcoplasmic proteins was not different, d) in children with
      chronic hypoxia the above atrio-ventricular differences persisted. Moreover, the
      proportion of the soluble collagenous fraction in the atria was significantly
      increased.

PMID- 8280722
TI  - The lymphatic route. IX. Distribution of recombinant interferon-alpha 2
      administered subcutaneously with oedematogenic drugs.
AB  - We have evaluated whether the addition of either bradykinin or histamine favours
      the lymphatic absorption of human recombinant interferon-alpha 2 (IFN-alpha 2)
      administered by the subcutaneous route. Subcutaneous administration of IFN-alpha
      2 with bradykinin enhances IFN absorption via both capillaries and lymphatics, so
      that either the plasma or lymph areas under the concentration curves (AUC)
      increase significantly up to 1751 +/- 483 and 1319 +/- 608 IU/ml/min respectively
      as compared to the respective AUC values (613 +/- 208 and 483 +/- 213 IU/ml/min)
      obtained after IFN injection in normal saline. Since the lymph AUC/plasma AUC
      ratios remain unaltered, there is no preferential lymphatic absorption of IFN
      alpha 2 after bradykinin administration. Dual-label experiments, 125I-IFN-alpha 2
      in saline and 131I-IFN-alpha in saline containing 200 micrograms histamine were
      injected subcutaneously into the left and into the right shank of the same
      animal, gave similar results. The kinetics of 125I and 131I acid-soluble
      radioactivity confirm that histamine favours both plasmatic and lymphatic
      absorption.

PMID- 8280723
TI  - Antioxidative state of the myocardium and kidneys in acute diabetic rats.
AB  - The influence of acute diabetes (8 days), induced by streptozotocin (45 mg.kg-1
      body weight) on myocardial and renal antioxidative conditions was investigated.
      The animals were given subtherapeutical doses of insulin (Interdep 6 U. kg-1 body
      weight, s.c.). Considerably increased levels of malondialdehyde (MDA), as well as
      of superoxide dismutase (SOD) and catalase (CAT) activity were found in the
      myocardium of diabetic animals. The oxidized glutathione (GSSG) level and
      glutathione peroxidase (GSH-PX) activity remained unchanged. The reduced
      glutathione (GSH) level as well as the activity of glutathione S-transferase
      (GST) were significantly lower. The activity of GSH-PX in the kidneys of diabetic
      rats increased by 60% and that of GST by 105%, respectively. CAT and SOD activity
      values were unchanged.

PMID- 8280724
TI  - Distribution of radioactivity of intraperitoneally administered 14C-leucine and
      14C-alanine in tissues of suckling lambs.
AB  - 14C-labelled leucine and alanine were administered intraperitoneally to suckling
      male lambs aged 30. The distribution of radioactivity was investigated in the
      liver, heart, quadriceps femoris muscle, subcutaneous adipose tissue, skin and
      expired air. Most of the radioactivity (per 1 g of dry tissue) was found in
      proteins of liver, followed by proteins of the heart, skin, muscle and adipose
      tissue. The radioactivity found in lipids and glycogen was much lower, with the
      exception of high radioactivity of leucine-derived lipids of the adipose tissue.
      Incorporation of alanine into proteins was lower than that of leucine. On the
      other hand, more alanine was oxidized to CO2 than leucine.

PMID- 8280725
TI  - Zinc and copper in the tissues and serum of cadmium intoxicated guinea-pigs:
      influence of vitamin C.
AB  - Cadmium in the dose of 1 mg/animal/day was administered to guinea-pigs in the
      form of CdCl2 dissolved in drinking water during short-term (5 weeks) and
      subchronic (12 weeks) experiments. Both the control and cadmium-treated groups
      were divided into two subgroups, according to low (2 mg/animal/day) and high (100
      mg/animal/day) vitamin C intake. Subchronic cadmium treatment caused copper
      deficiency indicated by a dramatic decrease of copper concentration in the liver
      and serum and by its moderate decrease in the testes and brain. Cadmium
      significantly increased zinc concentrations in the kidneys during the whole
      experiment and decreased the level of zinc in the serum after subchronic cadmium
      treatment. In the control groups, the levels of zinc and copper in the serum were
      lowered after 5 weeks of high vitamin C doses. High doses of vitamin C in cadmium
      treated guinea-pigs decreased the levels of copper in the testes, brain and
      serum. These observations suggest that cadmium intake in relatively high doses
      might potentiate the development of copper deficiency, and high doses of vitamin
      C aggravate, to a certain extent, copper depletion in some important organs and
      serum of guinea-pigs.

PMID- 8280726
TI  - Visual control of human stance on a narrow and soft support surface.
AB  - The influence of additional visual feedback (VF) on stance control was studied
      under conditions of changed afferent information from the foot sole and ankle
      joint due to different support surfaces. The changes of body sway amplitudes were
      analyzed and their frequency spectrum was established. The effect of visual
      feedback on the amplitude and frequency characteristics of human stance was
      manifested as: a) a decrease of the mean amplitude of body sway during visual
      feedback, corresponding to the decrease of power spectrum density (PSD) of
      stabilograms in the frequency range below 0.05 Hz, b) an increase of mean
      velocity of body sway corresponding to the increase of PSD of stabilograms in the
      frequency range of 0.4-1.5 Hz. The results showed that the improvement of the
      upright stance by additional visual feedback is mainly mediated through
      activation of postural muscles at the ankle level, or ankle strategy. The
      stabilization effect of VF on stance control is slight or negligible if the
      performance part in ankle joint (narrow support) was reduced.

PMID- 8280727
TI  - Effect of allopurinol and superoxide dismutase on indomethacin-induced gastric
      lesions in the rat.
AB  - Gastric lesions induced by indomethacin (20 mg.kg-1 i.p.) were studied in rats
      after a 24 hour fast. The size of the lesions was correlated with gastric
      vascular permeability (determined from the Evans blue concentration in the
      stomach tissue after its i.v administration) and with the rate of gastric
      emptying (determined from the phenol red concentration after its intragastric
      application). These changes were correlated with the prevention of gastric
      lesions by allopurinol (50 mg.kg-1) after a single dose or once daily for 3 days
      before indomethacin and by a single dose (15,000 U.kg-1) of superoxide dismutase
      (SOD). Indomethacin significantly increases the rate of gastric emptying
      concomitantly with gastric vascular permeability. The pretreatment of animals
      with allopurinol and SOD inhibits gastric lesions as well as gastric vascular
      permeability without changing gastric emptying which was increased after
      indomethacin administration. The inhibition of gastric lesion formation and
      gastric vascular permeability was more marked in rats pretreated with allopurinol
      for 3 days when compared with rats treated with a single dose of allopurinol
      only. These results support the suggestion that oxygen-derived free radicals
      contribute to the pathogenesis of indomethacin-induced gastric lesions.

PMID- 8280728
TI  - A method with enhanced sensitivity for temperature measurement in living tissues.
AB  - A system for the evaluation of temperature changes in living tissue at a
      dimensional level of a single cell is described. A glass micropipette the tip of
      which is filled with semiconducting glass (Rech et al. 1992), is used as a
      microsensor. The changes of conductivity of the sensor due to variations of
      temperature are evaluated by electronic circuitry based on the measurement of an
      AC current of sinusoidal waveform flowing through the sensor. Temperature changes
      in the range of 0.01 K can be detected in this way.

PMID- 8280729
TI  - Presidents' perceptions: an historic review of fifty years of the American Cleft
      Palate-Craniofacial Association.
AB  - This historic review of the American Cleft Palate-Craniofacial Association was
      written by the Historian charged by the ACPA Executive Council for the purpose of
      updating the history of the organization in honor of its 50th Anniversary. The
      data base for this review was the previously published 36-year history by
      Historian Charlotte Wells, the minutes of ACPA Executive Council meetings from
      1979 to 1993, and a questionnaire survey of the 32 living Past Presidents (with a
      90% return rate). This review highlights the important issues and critical
      decisions as recalled by Past Presidents. It also includes the recollection of
      humorous anecdotes, since the scholarly debate of this interdisciplinary
      organization is often brought to a positive interpersonal level through the good
      natured humor of many of its members.

PMID- 8280730
TI  - Image corrected cephalometric analysis (ICCA): design and evaluation.
AB  - Image corrected cephalometric analysis (ICCA) is a method for eliminating serial
      image parallax error. In a radiographic survey, image parallax is an inherent and
      random property of the two-dimensional image of the subject. Radiographs of the
      same subject taken at different times will be different in image parallax. This
      difference, parallax error, is routinely displayed between serial radiographic
      studies. Parallax error discourages the use of conventional serial cephalometric
      surveys for tracking and studying changes in discrete craniofacial structures
      lying outside the midsagittal plane, unilaterally disposed, or changing without
      bilateral symmetry. Anatomic outlines or discrete points of such structures would
      routinely display measurement perturbations caused by image parallax differences
      between surveys. The ICCA method eliminates this problem. Therefore, accurate
      serial measurements of bone marker point displacements are made possible with two
      dimensional reconstructions of points lying in three-dimensional space. The
      method of ICCA was tested for accuracy by using zero time serial cephalometric
      surveys of five subjects. Mean implant error of 0.12 mm (SD = 0.1) was found
      between predicted (ICCA) and actual measured implant movement caused by the image
      parallax error. After applying this method, bone marker movements are unlikely to
      be caused by parallax error between conventional serial cephalometric studies.
      Furthermore, displacement growth can be related to the relocation of composite
      growth outlines and midline anatomic landmarks. One plagiocephaly case and one
      hemifacial microsomia case were used to demonstrate ICCA for growth and treatment
      effect documentation.

PMID- 8280731
TI  - New technique for creating permanent experimental alveolar clefts in a rabbit
      model.
AB  - Alveolar bone grafting is an adjunctive procedure that has become increasingly
      popular in the rehabilitation of patients with cleft lip and palate. A histologic
      basis of the performance of bone grafts is required to evaluate properly
      different grafting materials. This, however, cannot be provided by clinical
      studies on humans. Therefore, an animal model with a simulated alveolar cleft is
      needed. A number of animal models has been previously proposed by other
      investigators. The problems associated with each model are presented and a
      surgical technique for the creation of permanent alveolar clefts in rabbits is
      described. Clinical and histologic findings 6 weeks postoperatively confirm the
      establishment of a 1-cm wide defect with oronasal communication and healthy
      epithelial lining. This animal model can be efficiently used for the testing of
      various bone grafting materials.

PMID- 8280732
TI  - Children with cleft lip/palate and mental retardation: a subpopulation of cleft
      craniofacial team patients.
AB  - This study compares a subpopulation of persons with cleft lip/palate who have
      mental retardation (n = 56) to those with normal learning (n = 420), at a large
      university-based cleft-craniofacial center. Many of the patients identified as
      having mental retardation in this sample have the diagnosis of isolated cleft
      palate (46.8%). Nearly half (46.3%) of the patients with mental retardation were
      found to have multiple anomalies, syndromes or associated medical findings.
      Common findings included cardiopulmonary defects, seizures, and deviations in
      head size. In this clinic population, mental retardation was found more commonly
      among African-American patients with clefts, than among Caucasian patients with
      clefts. Higher rates of facial disfiguration and impaired speech were found in
      patients with clefts and mental retardation. This research demonstrates that
      among a population of persons with cleft lip and/or cleft palate, there is a
      subpopulation of children who also have mental retardation. Craniofacial-cleft
      teams will need to develop strategies to address the special needs of this group
      of patients.

PMID- 8280733
TI  - Identification of children with and without cleft palate from tape-recorded
      samples of early vocalizations and speech.
AB  - Thirty judges (5 speech pathologists, 10 mothers of children with cleft palate,
      and 15 mothers of noncleft children) listened to 90 tape-recorded samples of
      early vocalizations/speech obtained from noncleft babies and babies with cleft
      palate. Each sample was classified by the judges as normal or abnormal. As a
      group, the speech pathologists classified only 60% of the cleft samples as
      abnormal and 59% of the normal samples as normal. The cleft and noncleft mother
      groups, on the other hand, classified 37% and 25% of the cleft samples as
      abnormal and 59% and 73% of the normal samples as normal. Poor interjudge
      agreement was evident within and across the three groups of judges. The poor
      reliability demonstrated by the speech pathologists in identifying babies with
      unrepaired clefts appeared related more to a difference in interpretation of the
      perceptual data than an inability to hear salient information.

PMID- 8280734
TI  - Clefts of the lip and palate in twins: use of DNA fingerprinting for zygosity
      determination.
AB  - The study of twins is a well-established method for evaluating the relative roles
      of heredity and environmental factors in the etiology of diseases. Conclusions
      depend on zygosity determination and on the classification of minor forms of
      diseases. This paper reports on ten (5 mono- and 5 dizygotic) out of thirteen
      twin pairs among 1039 patients with cleft lip and palate (n = 677) or cleft
      palate (n = 362). Zygosity was determined using "DNA fingerprinting" on blood
      samples in all 10 pairs and on cleft-associated tissue in one pair. Including
      minor forms of clefting, two of five pairs of monozygotic and two of five pairs
      of dizygotic twins of the same sex showed concordance. "DNA fingerprinting"
      should be established as a definitive method for zygosity determination, and the
      calculation of concordance rates should always include minor forms of diseases.

PMID- 8280735
TI  - Spheno-occipital synchondrosis in three-month-old children with clefts of the lip
      and palate: a radiographic study.
AB  - The literature has been focused on differences in craniofacial form and dimension
      in cleft lip and palate patients. No attention has been given to possible
      alterations in the spheno-occipital synchondrosis although the synchondrosis is
      regarded as an important maturity and growth center. The purpose of the present
      investigation was to examine if the spheno-occipital synchondrosis in children
      born with major complete clefts differs on lateral radiographs from that of
      children born with minor incomplete clefts. Fifty-seven three-month-old children
      with complete clefts of the lip, alveolus and palate and 42 three-month-old
      children with minor incomplete clefts of the lip were included in the study. The
      results of the comparison showed that children with complete major clefts had a
      broader spheno-occipital synchondrosis compared to children with a minor
      incomplete cleft of the lip, and that the distance from the superior part of the
      synchondrosis to the sella point was shorter in children with complete clefts.
      These findings could be related to a defect or a delay in maturity in the early
      development of the cartilaginous cranial base in children with major clefts.

PMID- 8280736
TI  - Neonatal cleft lip repair: the anesthesiologist's point of view.
AB  - Neonatal cleft lip repair is no longer an unusual procedure and several series
      have been published to date. We present our 3-year experience from the
      anesthesiologist's point of view. Preoperative evaluation, perioperative
      management, and postoperative problems are described. A thorough preoperative
      evaluation in order to exclude associated malformations (especially cardiac) and
      experience in neonatal anesthesia are essential for the sake of safety.

PMID- 8280737
TI  - Suitability of the iliac crest as a site for harvest of autogenous bone grafts.
AB  - Many donor sites have been advocated for obtaining cancellous bone to be used for
      grafting alveolar defects. Recently, some authors have suggested that the iliac
      crest site produced an unacceptably high degree of postoperative morbidity.
      Because of this morbidity, the use of other donor areas, e.g., rib, cranium, and
      mandible, are advocated. The iliac crest donor site for alveolar bone grafting
      has been common practice in our institution for years under the assumption that
      little or no postoperative morbidity occurred. To investigate and document the
      accuracy of our assumption, the charts of the most recent 50 consecutive patients
      receiving alveolar bone grafts, all of which used the iliac crest as a donor
      site, were reviewed. Postoperative pain, numbness, infection, paralysis, or long
      term disability were catalogued from the charts. In addition, a questionnaire was
      sent to the parents and patients requesting their perceptions of these
      parameters. In the cases reviewed, the average length of skin incision was 4.2
      cm. The average quantity of bone harvested was 4.1 cc. The usual hospitalization
      time was 2-3 days. No patients experienced serious or long-term complications at
      the surgical donor site. Immediate postoperative complications among the 50
      patients studied were limited to one hematoma, one stitch abscess, one case of
      swelling with pain, one erythema, and one 4-day fever accompanied by slight
      serosanguineous drainage. Information from the questionnaire suggests that most
      patients returned to full activity within 4-6 weeks. No patient reported any long
      term pain or disability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280738
TI  - Syngnathia: a report of two cases.
AB  - Syngnathia is a rare anomaly involving soft tissue or bony adhesions between the
      maxilla and mandible. Two cases of congenital syngnathia secondary to
      interalveolar soft tissue synechia are presented. These children present problems
      with airway protection and feeding in the immediate neonatal period. Most have
      multiple associated anomalies requiring concurrent management. Less than 50 cases
      have been described, most commonly in association with popliteal pterygium
      syndrome. Surgical management involves division of the adhesions in the first few
      days of life. Depending on the severity, these patients may present formidable
      anesthetic challenges. The prognosis is generally favorable in cases of soft
      tissue adhesions with eventual restoration of normal mandibular motion and
      function.

PMID- 8280739
TI  - Proximal deletion of the long arm of chromosome 1: [del(1)(q23-q25)].
AB  - A patient with bilateral complete cleft of the lip and palate (CLP) had a
      proximal deletion of the long arm of chromosome 1 (1q). This rare chromosomal
      abnormality was characterized by pre- and postnatal growth retardation,
      psychomotor retardation, and specific craniofacial and other systemic anomalies.
      There is a high incidence of CLP in proximal 1q deletion syndrome, especially
      bilateral CLP. Twelve other cases reported in the literature having this deletion
      and associated anomalies were reviewed.

PMID- 8280740
TI  - Submucous cleft palate with a discontinuous bony deformity.
AB  - An unusual submucous palatal cleft is presented. In addition to the usual triad
      of bifid uvula, posterior bony notching, and diastasis of the velar musculature,
      there was a linear bony cleft involving only the maxillary component of the hard
      palate. The palatine bone was intact between the posterior notch and the
      maxillary cleft. A discontinuous palatal cleft is an extremely rare deformity and
      is interesting because existing theories of cleft pathogenesis do not readily
      explain such a defect.

PMID- 8280741
TI  - A translation of Christopher Jacob Trew's article, "Observations presenting
      examples of missing palate. 1757.
AB  - The following "Observation" appeared (in Latin) in the Deutsche Akademie der
      Naturforscher Leopoldina of 1757 and to our knowledge has never been published in
      the English literature. We came across the report in the early 1970s while
      preparing the report "Cleft lip and cleft palate: one genetic system" (Chabora
      and Horowitz, 1974). The 1757 paper was translated by a member of the Columbia
      University Greek and Latin Department, but reached us too late for inclusion in
      our references. Forgotten for many years, the paper, and its translation,
      recently came to light in our files. Christopher Jacob Trew's clear description
      of penetrance and expressivity in a kindred in which both cleft lip and palate
      and isolated cleft palate are segregating may be something of an historic
      curiosity at this point, but we expect that others will enjoy reading this early
      example of a careful and thoughtful pedigree study.

PMID- 8280742
TI  - Sphingolipid breakdown products: anti-proliferative and tumor-suppressor lipids.
AB  - The sphingolipids are a family of lipids found ubiquitously in eukaryotic cell
      membranes. Within the last decade sphingolipids have emerged as active
      participants in the regulation of cell growth, differentiation, transformation,
      and cell-cell contact. A prototypic sphingolipid signalling pathway is the
      'sphingomyelin cycle,' in which membrane sphingomyelin is hydrolyzed in response
      to extracellular stimuli, generating the putative second messenger ceramide.
      Ceramide, in turn, is thought to propagate the signal into the cell interior by
      the activation of a phosphatase. It is likely that other sphingolipids are
      components of similar signalling cycles, generating a variety of lipid messengers
      which participate in as yet undefined pathways. Sphingosine, for example, is a
      potential breakdown product of all sphingolipids, and is well-known for its
      pharmacologic inhibition of protein kinase C. However, it is becoming apparent
      that sphingosine is active in multiple signalling cascades that are independent
      of protein kinase C, including effects on fibroblast cell growth and the
      regulation of the retinoblastoma tumor suppressor protein. Similarly, lyso
      sphingolipids, while comprising only a minor fraction of the cell's total
      sphingolipids, are turning out to have biological effects which warrant their
      investigation as potential signalling molecules. A distinguishing characteristic
      of sphingolipid breakdown products is their apparent participation in anti
      proliferative pathways of cell regulation. Thus, sphingolipid breakdown products
      can be found to play roles in growth inhibition, induction of differentiation,
      and programmed cell death. In coordination with other cellular signal
      transduction pathways, the sphingolipid breakdown products may be the harnesses
      on cell growth and may also contribute to the suppression of oncogenesis.

PMID- 8280743
TI  - Ribosome-inactivating proteins from plants.

PMID- 8280744
TI  - The molecular and cell biology of glycosyltransferases.

PMID- 8280745
TI  - Liposomes as agents of DNA transfer.

PMID- 8280746
TI  - Study of structure-activity relationship of fasciculin by acetylation of amino
      groups.
AB  - Dendroaspis angusticeps (green mamba) has two toxins, fasciculins, that are non
      competitive inhibitors of acetylcholinesterase. Amino groups of fasciculin 2 were
      acetylated with acetic anhydride. The monoacetyl derivatives of the epsilon-amino
      groups (Lys 25, 32, 51 and 58) retained between 28 and 43% of the initial
      activity and that of the alpha-amino group 72%. Acetylation of Lys 25 that has
      the most reactive amino group decreased the activity by 65% apparently without
      producing structural perturbations, since the circular dichroism spectrum was not
      affected. The three-dimensional structure shows a cationic cluster formed by Lys
      32, 51, Arg 24 and 28. A comparison of 175 sequences of homologous toxins shows
      that Lys 32 is unique for fasciculin. Acetylation of lysine residues in the
      cluster had a large effect and reduced the activity by 72% (Lys 32) and 57% (Lys
      51). This suggests an important role for the cationic cluster. Lys 25 together
      with Lys 32 and 51 were, therefore, assumed to be in the active site.

PMID- 8280747
TI  - Acute effects of insulin-like growth factor-I (IGF-I) on bone protein synthesis
      in rats.
AB  - The acute systemic effects of IGF-I on bone protein metabolism from hormonally
      intact rats have been investigated by measuring the fractional rate of protein
      synthesis. The animals received a single subcutaneous injection of rhIGF-I (100
      micrograms). Treatment with IGF-I increased the rate of tibia protein synthesis
      (Ks) while plasma glucose and insulin concentrations were decreased. These
      results are in favor of an endocrine role of IGF in stimulating bone growth.

PMID- 8280748
TI  - Cellular protein receptors of maculosin, a host specific phytotoxin of spotted
      knapweed (Centaurea maculosa L.).
AB  - Maculosin (the diketopiperazine, cyclo (L-Pro-L-Tyr)) is a host specific
      phytotoxin produced by Alternaria alternata on spotted knapweed (Centaurea
      maculosa L.). Receptors for this phytotoxin have been isolated from spotted
      knapweed. Knapweed leaves possess most of the maculosin-binding activity in the
      cytosolic fraction. However, activity was also observed in the whole membrane
      fraction of the leaf. The binding component of the cytosolic fraction was
      identified as a protein(s) because of its heat-lability and sensitivity to
      proteases. A 16-fold purification of a toxin-binding protein was carried out by
      ammonium sulfate fractionation, and Sephadex G-200, and maculosin-affinity column
      chromatography. The affinity column was prepared with epoxy activated Sepharose
      6B to which the phenolic group of maculosin was attached. The receptor was
      estimated to contain more than one binding protein by native and SDS-PAGE. At
      least one of the maculosin-binding proteins was identified as ribulose-1,5
      biphosphate carboxylase (RuBPcase).

PMID- 8280749
TI  - Effect of cAMP on the association of small GTP-binding proteins with the
      cytoskeleton of human platelets.
AB  - Following activation of human platelets changes in cytoskeletal organization
      occur: some proteins, which are present in the cytosol or membrane-associated in
      resting platelets, are recovered in the Triton-insoluble residue in activated
      cells. Assembly and disassembly of complex effector units on the membrane and
      inside cells is under the control of low molecular weight GTP-binding proteins,
      particularly those in the ras family. We investigated the interaction of small
      GTP-binding proteins with the platelet cytoskeleton and the effect of high cAMP
      levels on these interactions. At least two GTP-binding proteins of 24 and 28 kDa
      were detected in the Triton-insoluble residue of resting platelets. Stimulation
      of platelets with thrombin or concanavalin A (Con A), under non-aggregating
      conditions, resulted in increased 24 kDa protein-bound GTP, which also contained
      a significant amount of rap1B. High cAMP levels differently affected this
      interaction depending on the type of agonist used. cAMP increased association of
      G-proteins with the cytoskeleton following Con A-activation, while it decreased G
      proteins interaction after thrombin stimulation. The activation did not influence
      the cAMP-dependent phosphorylation of rap1B. No phosphoprotein corresponding to
      rap1B could be detected in the Triton-insoluble residues, however. These findings
      could be related to the different mechanisms of cytoskeletal protein recruitment
      in platelets activated with either thrombin or Con A.

PMID- 8280750
TI  - Analysis and modelling of the structures of beta-cyclodextrin complexes.
AB  - A systematic computer graphics study of all available beta-cyclodextrin crystal
      structures has been carried out specifically to aid in the modelling and design
      of beta-cyclodextrin-drug complexes. The analyses show that the basic
      conformation of the molecule remains constant among natural, mono-substituted and
      partially permethylated beta-cyclodextrins, with major changes observed only in
      the case of full permethylation. In all the structures, however, there are no
      significant perturbations caused by guest molecule inclusion. On the basis of
      these observations models are proposed for the structures of beta-cyclodextrin
      indomethacin complexes, the principal features of which are shown to be
      consistent with the data obtained in 1H-NMR studies.

PMID- 8280751
TI  - Glycosylation reactions in Plasmodium falciparum, Toxoplasma gondii, and
      Trypanosoma brucei brucei probed by the use of synthetic peptides.
AB  - Synthetic peptides were used to probe O- and N-glycosylation reactions in cell
      free systems of the parasitic protozoa Plasmodium falciparum, Toxoplasma gondii,
      and Trypanosoma brucei brucei. O-Glycosylation of the peptide Pro-Tyr-Thr-Val-Val
      was observed with lysates from all organisms. However, the spectrum of sugars
      transferred from their respective nucleotide or dolichol-phosphate derivatives to
      the peptide varied greatly according to the parasite. N-glycosylation of the
      peptides N-Bz-Asn-Gly-ThrNH2 and DNP-Arg-Asn-Ala-Thr-Ala-ValNH2 by exogenous
      radioactive dolichol-pyrophosphate linked oligosaccharide donors was observed
      only when lysates of T. gondii or T. b. brucei were used, but not in P.
      falciparum. To assay for endogenous N-glycosylation donors, the radiolabeled
      tripeptide [3H]Ac-Asn-Gly-ThrNHMe was used as acceptor. The peptide was N
      glycosylated only by T. gondii and T. b. brucei preparations. Only in these
      latter two parasites dolichol-cycle mannosyltransferase activity was demonstrated
      by the elongation of exogenous radiolabeled dolichol-PP-chitobiose. The data
      substantiate the occurrence of protein O-glycosylation in parasitic protozoa and
      the exceptional absence of protein N-glycosylation in the asexual
      intraerythrocytic stage of the malaria parasite, P. falciparum.

PMID- 8280752
TI  - Abnormal metabolism of S-adenosyl-L-methionine in hypoxic rat liver. Similarities
      to its abnormal metabolism in alcoholic cirrhosis.
AB  - S-Adenosylmethionine (AdoMet) is an important biologic methylating agent for
      nucleic acids, phospholipids, biologic amines, and proteins. Previous studies
      indicated that hepatic AdoMet synthetase and hepatic levels of AdoMet are
      subnormal in patients with alcoholic cirrhosis. This abnormality limits the
      patients' capacity to convert phosphatidylethanolamine to phosphatidylcholine by
      way of phosphatidylethanolamine-N-methyltransferase (PEMT). Because alcoholic
      consumption appears to be associated with hepatic hypoxia, we previously measured
      AdoMet concentration in liver cells under acute hypoxia and found the level to be
      decreased substantially. In the present study, we determined whether a similar
      metabolic abnormality was also observed in rats maintained under physiologic
      hypoxia for 9 days and administered standard rat chow. The study showed that
      AdoMet levels in hypoxic rat (ave +/- SD) were significantly lower than those in
      the control (36.8 +/- 11.6 vs. 60.4 +/- 2.3 nmol/g liver; P < 0.05). Also
      significantly lower in the hypoxic group were the activities of AdoMet synthetase
      (0.60. +/- 0.07 vs. 0.97 +/- 0.20 U; P < 0.05) and PEMT (26.2 +/- 4.2 vs. 35.6 +/
      5.8 U; P < 0.02). The mRNA levels of AdoMet synthetase also declined in hypoxia
      indicating that hypoxia may modulate the gene expression of hepatic AdoMet
      synthetase. Thus, in vivo hypoxia may have an important effect on 1-carbon
      metabolism.

PMID- 8280753
TI  - Barley beta-glucosidase: expression during seed germination and maturation and
      partial amino acid sequences.
AB  - Unlike most of the hydrolytic enzymes that participate in endosperm mobilization,
      beta-glucosidase of barley (Hordeum vulgare) seeds does not increase during
      germination, even in the presence of exogenously added gibberellic acid. However,
      the germination process affects the physical properties of beta-glucosidase in
      terms of charge and apparent molecular weight. Analysis of developing barley
      grains shows that the enzyme is synthesized two weeks before maturation and is
      stored in the endosperm of the dry dormant seed. Partial amino acid sequencing of
      the purified beta-glucosidase demonstrates significant similarity between the
      barley enzyme and beta-glycosidases that belong to family 1 of glycosyl
      hydrolases.

PMID- 8280754
TI  - Conformational changes of bovine serum albumin upon its adsorption in dodecane-in
      water emulsions as revealed by front-face steady-state fluorescence.
AB  - Front-face fluorescence spectroscopy was used to characterise dodecane-in-buffer
      (0.1 M phosphate buffer; pH = 7.6) emulsions stabilised by bovine serum albumin
      (BSA). A 15-nm blue-shift of the emission maximum of the adsorbed protein and a
      significant increase of its fluorescence quantum yield were observed. The
      contribution of tyrosyl residues to total fluorescence was tentatively evaluated
      from different spectra and an R ratio taking into account the stray-light
      interference; R increased upon BSA absorption but the Tyrosine contribution
      remained weak in all cases. Thus, conformational changes of the protein take
      place upon BSA adsorption onto the dodecane-water interface. They involve
      modifications in the environment of the protein aromatic amino acids especially
      of the tryptophanyl residues which are displaced to a more hydrophobic location.
      Moreover, the proportions of absorbed and non-adsorbed BSA in emulsions can be
      estimated from the position of the emission maximum.

PMID- 8280755
TI  - Oxidative stress modifies the activity of cardiac sarcolemmal phospholipase C.
AB  - We have examined the direct effects of oxidant metabolites on cardiac sarcolemmal
      phosphoinositide phospholipase C which transduces signals from various receptors
      for the modulation of intracellular Ca2+ levels. The enzyme activity in rat
      cardiac sarcolemmal membranes that had been preincubated (10 min; 37 degrees C)
      with xanthine-xanthine oxidase, a superoxide anion generating system, was not
      significantly affected. The addition to this system of superoxide dismutase,
      which converts superoxide anion to hydrogen peroxide (H2O2), resulted in a
      significant decrease of the enzyme activity in comparison with control values.
      Such decrease was fully prevented by catalase. Preincubation of sarcolemma with
      hypochlorous acid also gave a significant inhibition of phospholipase C, which
      was counteracted by the synthetic thiol reducer dithiothreitol. H2O2-pretreatment
      induced a concentration-dependent inhibition of the enzyme which was prevented by
      catalase but not by the iron chelator deferoxamine. Dithiothreitol was able to
      protect against, as well as to recover the enzyme activity from the H2O2 effects.
      These data suggest that superoxide anions and hydroxyl radicals did not interfere
      with phospholipase C activity, and that the nonradical oxidants, H2O2 and
      hypochlorous acid, may have acted through oxidation of thiol (SH) groups. The
      existence of reactive SH groups associated with the enzyme was confirmed by the
      inhibitory effects of SH modifiers (p-chloromercuriphenylsulfonic acid, 5'5'
      dithio-bis(2-nitrobenzoic acid), N-ethylmaleimide and methyl
      methanethiosulfonate), which were prevented and in some cases also reversed by
      dithiothreitol. The biological reducer glutathione (GSH) was not able to recover
      the H2O2-induced inhibition of phospholipase C, whereas its oxidized form (GSSG)
      decreased the enzyme activity both in control and H2O2-pretreated membranes. The
      enzyme was active in a wide range of GSH/GSSG redox states, but H2O2 pretreatment
      narrowed this range. The results showed that oxidative stress changed the redox
      state of sarcolemmal phospholipase C, and this deactivated the enzyme. The
      oxidants' concentrations that significantly impaired phospholipase C in this
      study were compatible with those occurring in vivo during ischemia-reperfusion
      [Am. J. Med. 91(Suppl. 3C):235, 1991]. This supports the possibility that
      alteration of the receptor-associated phospholipase C may be a factor in the
      oxidant-related dysfunction of the ischemic-reperfused heart.

PMID- 8280756
TI  - Involvement of phospholipids in the intoxication mechanism of botulinum
      neurotoxin.
AB  - Phospholipids were examined for their potential to interact with botulinum
      neurotoxin by an in vivo toxin-inactivation assay and a direct binding assay on a
      thin layer plate. Type E neurotoxin was inactivated by negatively charged
      phospholipids, phosphatidylserine (PS) and phosphatidylinositol (PI). The
      toxicity of the neurotoxin was not affected by phosphatidylcholine (PC) without
      an electric charge or phosphatidylethanolamine (PE) with a positive electric
      charge. The neurotoxin bound directly to PS and PI but not to PC or PE. These
      results suggest that the negatively charged phospholipids in the cell membranes
      are involved in the intoxication mechanism of botulinum neurotoxin. The
      phospholipids PS and PI were tested for their potential to interact within three
      domains [L, H-1, and H-2] which compose the neurotoxin. All three domains bound
      to PS; whereas, PI specifically accepted the binding of the H-1 domain relative
      to the penetration of the neurotoxin into the lipid membrane. In this paper, we
      discuss the interaction between the neurotoxin and the lipid membrane in the
      intoxication mechanism.

PMID- 8280757
TI  - Isolation and characterization of TsTX-V, a new neurotoxin from Tityus serrulatus
      scorpion venom which delays the inactivation of Na+ channels.
AB  - TsTX-V, a new neurotoxin from Tityus serrulatus scorpion venom able to induce a
      prolongation of the inactivation of Na+ channels, has been purified to
      homogeneity. The venom was chromatographed on CM-cellulose-52 and 13 fractions
      were first collected. A subsequent stepwise elution chromatography of fraction XI
      afforded, among other toxins, highly purified TsTX-V, which showed a single band
      by PAGE, SDS-PAGE or isoelectric focusing, a distinctive amino acid composition,
      mol. wt. = 7230, pI = 8.0 and i.v. LD50 = 94 +/- 7 micrograms/kg in mice. TsTX-V
      induced a long lasting hypertension in anesthetized rats and prolonged the action
      potential of the B fibers of the rabbit vagus nerve at 0.03 microgram/ml. At 0.3
      microgram/ml and higher concentrations it caused also a nerve depolarization.
      These effects on nerve membranes were irreversible and could be suppressed by
      tetrodotoxin (200-500 nM). Nerve fibers depolarized by high extracellular K+(15
      30mM) concentrations still displayed long duration action potentials after TsTX-V
      treatment. It is suggested that TsTX-V blocks the Na+ channel inactivation system
      probably as an alpha-toxin.

PMID- 8280758
TI  - Retinoic acid inhibition of thyroxine binding to human transthyretin.
AB  - All-trans retinoic acid is a potent inhibitor of [125I]-thyroxine (T4) binding to
      human erythrocyte membranes and can block the activation by thyroid hormone of
      erythrocyte Ca(2+)-ATPase [J. Biol. Chem. (1989) 264, 687-689]. In the present
      studies, retinoic acid was examined for its ability to displace thyroxine from
      binding sites on human transthyretin (TTR). Scatchard analysis of [125I]T4
      binding to purified TTR, determined by equilibrium dialysis, revealed two classes
      of binding sites with association constants of 3.2 x 10(9) M-1 and 8.1 x 10(6) M
      1. All-trans retinoic acid also displaced [125I]T4; 40% of the specifically bound
      [125I]T4 was displaced at a retinoic acid concentration of 2 x 10(-5) M. Analysis
      of the high affinity T4 binding site suggests that the Ka for retinoic acid to
      that site is approx. 10(7) M-1. 8-Anilinonaphthalene-1-sulfonate (ANS), a
      strongly fluorescing dye, binds to the thyroxine binding sites on TTR. T4 and
      3,5,3'-L-triiodothyronine (T3) shifted the fluorescence emission maximum and
      intensity of an ANS-TTR solution toward the spectrum obtained from uncomplexed
      ANS. All-trans retinoic acid caused a similar shift in the emission spectrum of
      ANS, but was less potent than T4. Retinol failed to quench the emission intensity
      of the ANS-TTR complex, while 13-cis-retinoic acid was less effective than all
      trans retinoic acid.

PMID- 8280759
TI  - Chemical modification of arginine and lysine residues in coenzyme-binding domain
      of carbonyl reductase from rabbit kidney: indomethacin affords a significant
      protection against inactivation of the enzyme by phenylglyoxal.
AB  - Carbonyl reductase from rabbit kidney was inactivated by phenylglyoxal (PGO) and
      2,4,6-trinitrobenzenesulfonate sodium (TNBS). NADP+ protected the enzyme from the
      inactivations by PGO and TNBS, suggesting that essential arginine and lysine
      residues are located in coenzyme-binding domain of the enzyme. Judging from the
      effects of PGO-treated enzymes in the presence and in the absence of NADP+ on the
      fluorescence intensity of NADPH, one essential arginine residue in coenzyme
      binding domain was found to have a role in the binding of NADPH to the enzyme.
      Indomethacin afforded a significant protection against inactivation of the enzyme
      by PGO, whereas it could not protect the enzyme from the inactivation by TNBS. It
      is reasonable to postulate that indomethacin interacts at least in part with or
      near one essential arginine residue in coenzyme-binding domain of carbonyl
      reductase from rabbit kidney.

PMID- 8280760
TI  - Production and characterization of monoclonal antibodies directed against bovine
      milk fat globule membrane (MFGM).
AB  - Nine hybridomas secreting monoclonal antibodies (mAbs) to bovine milk fat globule
      membrane (MFGM) were produced from spleen cells of three immunized BALB/c mice.
      Several MFGM antigens recognized by some mAbs were identified as a 120 kDa
      protein and 67 kDa (butyrophilin), 57 kDa (PAS-6), 53 kDa (PAS-7), 33 kDa
      glycoproteins. The other mAbs secreted by four independent hybridoma clones
      recognized many broad bands ranging from 20 to 200 kDa. The 120 kDa protein and
      67 kDa, 57 kDa, 53 kDa glycoproteins were detected by each mAb in the plasma
      membrane fraction prepared from a lactating bovine mammary gland. Moreover,
      mammary gland epithelium of a thin section was specifically stained with these
      mAbs, indicating that these mAbs directed against MFGM recognized membrane
      proteins and glycoproteins of lactating mammary epithelial cells. Upon heating of
      the MFGM in phosphate buffer, pH 7.4 at 100 degrees C for 10 min, the antigens
      still retained most of its reactivity to these mAbs, whereas, proteolytic
      cleavage by trypsin and chymotrypsin strongly reduced its reactivity to these
      mAbs by 60% or more except for two mAbs which recognized the 57 and 53 kDa
      glycoproteins, respectively.

PMID- 8280761
TI  - The cell wall polysaccharide of Actinoplanes sp. INA 3697 composed of 2-acetamido
      2-deoxy-beta-D-mannopyranosyl-(1-->3)-2-acetamido-2-deoxy-a lpha-D-glucopyranosyl
      1-phosphate repeating units.

PMID- 8280762
TI  - Molecular and biochemical analyses of fatty acid transport, metabolism, and gene
      regulation in Escherichia coli.

PMID- 8280763
TI  - Acyl transfer reactions associated with cis Golgi apparatus of rat liver.
AB  - Isolated Golgi apparatus, highly purified from rat liver, were found to contain
      an acyl transfer activity capable of restoring the acyl chains of the
      lysophospholipid products of the action of phospholipase A2 on
      phosphatidylcholine. The activity was located primarily in cis and medial Golgi
      apparatus fractions, had a pH optimum of 6.0 to 7.5 and was stimulated by various
      acyl-CoA derivatives but not by fatty acids plus ATP. The activity, determined
      from the conversion of [14C]lysophosphatidylcholine to [14C]phosphatidylcholine,
      was unaffected by EGTA, inhibited by manoalide at high concentrations (0.2 mM),
      and temperature-dependent. Temperature dependency, however, showed no definite
      transition temperature over the range 15 to 37 degrees C. The results
      demonstrated that cis Golgi apparatus membranes have the enzymatic capacity to
      restore fatty acids lost from phospholipids through the action of phospholipase
      A. The latter has been previously suggested to occur at the cis Golgi apparatus
      membranes based on analyses of cell-free transfer of radiolabeled
      phosphatidylcholine.

PMID- 8280764
TI  - High-sensitive chemiluminescent assay for cholesterol.
AB  - Chemiluminescent measurement of cholesterol can be performed in various
      biological tissues and fluids. The method described in this study has a
      sensitivity of 54 pmol. The tissue samples used for the determination of
      cholesterol can be reduced to as little as 1 mg and assay can be performed on
      diluted biological fluids, allowing sampling of plasma or serum as little as 5
      microliters. Cholesterol is solubilized in sodium cholate and aliquots are added
      to a reaction mixture containing cholesterol oxidase, luminol and peroxidase.
      Cholesterol oxidase, in the presence of cholesterol yields H2O2 which produces
      light in presence of luminol and peroxidase. Emitted light is quantified at a
      wavelength of 420 nm by means of a photomultiplier. Optimal conditions of the
      assay were determined and examples of cholesterol determinations, in blood plasma
      and nervous tissues, are presented.

PMID- 8280765
TI  - Digestive lipases: inactivation by phosphonates.
AB  - Phosphonates mimicking the transition state which occurs during carboxyester
      hydrolysis were synthesized and investigated as potential inactivators of human
      pancreatic (HPL) and gastric (HGL) lipases. Their efficiency as inactivators was
      studied on the basis of the alkyl chain length, the nature of the leaving group
      and the influence of the ester substituent. In each case, HGL was found to be
      more sensitive than HPL towards these phosphonates. The released p-nitrophenol to
      enzyme ratio indicates that a 1:1 complex was formed. In the absence of
      substrate, the most powerful inactivator was O-methyl O-(p-nitrophenyl) n
      pentylphosphonate (4A), which has a short alkyl chain, a small methoxy
      substituent and a good leaving group.

PMID- 8280767
TI  - Structural elucidation of new phenolic glycolipids from Mycobacterium
      tuberculosis.
AB  - From one clinical isolate of Mycobacterium tuberculosis, two new phenolic
      glycolipids(PGLs) were obtained as its major PGLs. These were dimycocerosyl
      esters of 2,4-di-O-methyl-fucopyranosyl-(alpha 1-->3)-rhamnopyranosyl-(alpha 1-
      >3)-2-O-methyl-rhamnopyranosyl-(alpha 1-->)-phenolphthiocerol A and 
      phenolphthiotriol A, which were produced by this strain at a ratio of about 5:1.
      Another clinical isolate of this species was found to produce PGL-tb1 and its
      analogue, 2,3,4-tri-O-methyl-fucopyranosyl-(alpha 1-->3)-rhamnopyranosyl-(alpha 1
      ->3)-2-O-methyl-rhamnopyranosyl-(alpha 1-->)-phenolphthiotriol A at a ratio of
      about 1:3. The fact that different strains of M. tuberculosis produce chemically
      different PGLs as their major PGLs may be related to the diversity of virulence
      of the clinical isolates of M. tuberculosis.

PMID- 8280766
TI  - Developmental regulation of re-uptake of phosphatidylcholine by type II alveolar
      epithelium.
AB  - Type II alveolar epithelia produce, store and secrete pulmonary surfactant, a
      phospholipid and protein mixture which stabilizes alveoli at low lung volumes
      and, thereby, prevents alveolar collapse. We determined the developmental changes
      in the uptake, metabolism and reutilization of surfactant-related phospholipid in
      primary cultures of type II cells derived from fetal rat lung. Primary cultures
      of fetal and neonatal type II cells were incubated in media containing labelled
      liposomes. After the incubation phospholipids were extracted from the cells and
      uptake of label was analyzed. Re-uptake of radiolabelled dipalmitoyl
      phosphatidylcholine (DPPC) was concentration-dependent in undifferentiated fetal
      cells, differentiated fetal cells and neonatal cells. Re-uptake of DPPC by
      undifferentiated fetal cells was lower than re-uptake by both differentiated
      fetal and neonatal cells at 15 and 75 microM PC. Binding of DPPC to the cell
      surface involved a protein interaction, since trypsin was able to dissociate this
      trypsin-releasable fraction from internalized label. Undifferentiated fetal,
      differentiated fetal and neonatal cells all exhibited approx. 50% metabolic
      degradation of internalized phospholipid. Degraded lipids were reutilized in the
      synthesis of phosphatidylglycerol, but neonatal cells resynthesized twice as much
      phosphatidylglycerol as did undifferentiated fetal cells. These are the first
      studies which show that morphologically undifferentiated fetal type II cells are
      capable of the uptake of surfactant phospholipid as well as the degradation and
      reutilization of internalized phospholipid. Re-uptake, degradation and
      reutilization of internalized phospholipid appear to be under developmental
      control.

PMID- 8280768
TI  - Regulation of cholesterol uptake in the rat intestinal cell line.
AB  - A new model to study cholesterol absorption in the rat intestinal cells is
      described. Rat intestine epithelial cells IRD98 were incubated with mixed
      micelles containing bile acid, phospholipid, cholesterol or its nonabsorbable
      analogue, sitosterol, and trace amounts of [3H]cholesterol or [14C]sitosterol.
      Cholesterol and sitosterol uptake was then determined following lipid extraction;
      specific cholesterol uptake was determined as the difference between cholesterol
      and sitosterol uptake. Cholesterol, but not sitosterol, uptake was time- and dose
      dependent and saturable. Loading of cells with non-lipoprotein cholesterol
      reduced cholesterol, but not sitosterol, uptake in a dose-dependent manner. In
      contrast, treatment of cells with an inhibitor of cholesterol synthesis,
      lovastatin, stimulated cholesterol, but not sitosterol, uptake in a dose
      dependent manner. Treatment of cells with palmitic, caproic and oleic acids up
      regulated specific cholesterol uptake, while linoleic and stearic acids had an
      opposite effect. None of the fatty acids affected sitosterol uptake.

PMID- 8280769
TI  - Modulation by dietary oils and clofibric acid of arachidonic acid content in
      phosphatidylcholine in liver and kidney of rat: effects on prostaglandin
      formation in kidney.
AB  - The manipulation of 20:4(n - 6) contents in phosphatidylcholine of liver and
      kidney of rats by dietary oils and p-chlorophenoxyisobutyric acid (clofibric
      acid) as well as the effects on the formation of prostaglandin E2 in kidney were
      studied. Three groups of rats were fed diets that contained either safflower oil
      (SO) or perilla oil (PO) or fish oil (FO) for 1 week. Each dietary group was
      divided into two groups. One group continued the same diet for another 1 week;
      the second group continued the same diet and received subcutaneous injections of
      clofibric acid once a day for 1 week. The content of 20:4(n - 6) in hepatic
      phosphatidylcholine was markedly lowered by feeding either FO or PO and was
      further decreased by the administration of clofibric acid. Feeding either FO or
      PO lowered the content of 20:4(n - 6) in hepatic phosphatidylethanolamine,
      whereas clofibric acid increased it. The decrease in the level of 20:4(n - 6) in
      serum phospholipid was produced by feeding either FO or PO and by the
      administration of clofibric acid as well. There was a high correlation for the
      levels of 20:4(n - 6) between hepatic phosphatidylcholine and serum phospholipid.
      The changes brought about by dietary oils and clofibric acid in renal
      phosphatidylcholine was similar to those observed in liver. The content of 20:4(n
      - 6) in renal phosphatidylcholine was highly correlated with the level of 20:4(n 
      6) in serum phospholipid. Other phospholipids in kidney responded less
      sensitively to the manipulation by dietary oils and clofibric acid. These results
      suggest that the level of 20:4(n - 6) in renal phosphatidylcholine is regulated
      by the level of 20:4(n - 6) in hepatic phosphatidylcholine through the changes in
      serum level of 20:4(n - 6). Formation of prostaglandin E2 in kidney slices was
      dependent on the content of 20:4(n - 6) in renal phosphatidylcholine.

PMID- 8280770
TI  - Ethanol inhibits zymosan-stimulated eicosanoid production in mouse peritoneal
      macrophages.
AB  - Resident peritoneal macrophages synthesized and released eicosanoids when
      challenged by zymosan, a phagocytosable particle. Incubation of these cells with
      ethanol resulted in dose-dependent inhibition of arachidonic acid release and
      eicosanoid generation in response to zymosan. Ethanol affected the extent but not
      the ratio of eicosanoids released. When assayed in a cell-free system, endogenous
      phospholipase A2 activity was neither affected by the presence of ethanol in the
      incubation medium nor by preincubation of the cells with ethanol. Ethanol also
      inhibited arachidonic acid release in response to phorbol myristate acetate, a
      compound that, like zymosan, triggered a pertussis-toxin-sensitive response. When
      cells that had been previously treated with pertussis toxin were used, no further
      inhibitory effect of ethanol was seen in response to both zymosan and phorbol
      myristate acetate. On the other hand, ethanol had no effect on arachidonic acid
      release stimulated by ionophore A23187 or lipopolysaccharide, two compounds that
      triggered a pertussis-toxin-insensitive response. Moreover, ethanol was able to
      nearly abolish arachidonic acid release in response to fluoroaluminate, a direct
      activator of G-proteins. Altogether, the results of this study suggest that
      ethanol inhibits zymosan-stimulated eicosanoid production by interacting with a G
      protein--or a G-protein-mediated process--that is critically involved in
      arachidonic acid mobilization.

PMID- 8280771
TI  - Platelet-aggregating effects of platelet-activating factor-like phospholipids
      formed by oxidation of phosphatidylcholines containing an sn-2-polyunsaturated
      fatty acyl group.
AB  - Previously, we reported the formation of four kinds of phosphatidylcholines (PC)
      with a short-chain monocarboxylate, dicarboxylate, dicarboxylate semialdehyde or
      omega-hydroxymonocarboxylate group by oxidation of PCs containing polyunsaturated
      fatty acid (PUFA) in an FeSO4/ascorbate/EDTA system. In this study, we identified
      these novel phospholipids by GC-MS as oxidation products of two alkyl ether
      linked PCs, 1-O-hexadecyl-2-docosahexaenoyl and 1-O-hexadecyl-2-arachidonoyl-sn
      glycero-3- phosphocholine (GPC). The sn-2-acyl moieties of oxidatively fragmented
      PCs derived from PCs containing docosahexaenoate were one methylene unit shorter
      than those detected as major oxidation products of PCs containing arachidonate.
      The platelet-aggregations induced by the oxidized PCs were all inhibited by FR
      900452, an antagonist of platelet activating factor (PAF). The PAF-like activity
      of oxidized 1-O-hexadecyl-2-docosahexaenoyl-GPC, which was equivalent of 1372 +/-
      262 pmol 16:0-PAF/mumol starting PC, was 5 times that of oxidized 1-O-hexadecyl-2
      arachidonoyl-GPC and 150 times that of oxidized 1-palmitoyl-2-docosahexaenoyl
      GPC, suggesting that both an sn-1-alkyl ether linkage and an sn-2-acyl group with
      a short chain length are important structural requirements for induction of
      platelet aggregation. These possibilities were confirmed by experiments on the
      platelet-aggregating activities of synthetic PAF-like compounds. Quantitative
      measurements by GC-MS of PAF-like phospholipids formed by lipid peroxidation and
      the activities of synthetic PAF-like phospholipids, suggested that the activities
      of most oxidized PCs containing PUFA were ascribable to those of PCs with an sn-2
      short-chain monocarboxylate group.

PMID- 8280772
TI  - Comparison of 1-O-alkyl-, 1-O-alk-1'-enyl-, and 1-O-acyl-2-acetyl-sn-glycero-3
      phosphoethanolamines and -3-phosphocholines as agonists of the platelet
      activating factor family.
AB  - Four naturally occurring platelet-activating factor (PAF) analogs, 1-alk-1'-enyl
      2-acetyl-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-acetyl-sn-glycero-3
      phosphocholine, 1-octadecanoyl-2-acetyl-sn-glycero-3-phosphocholine, and 1-alkyl
      2-acetyl-sn-glycero-3-phosphoethanolamine, stimulated human neutrophils (PMN) to
      mobilize Ca2+, degranulate, and produce superoxide anion. They were,
      respectively, 5-, 300-, 500-, and 4000-fold weaker than PAF in each assay;
      inhibited PMN-binding of [3H]PAF at concentrations paralleling their biological
      potencies; and showed sensitivity to the inhibitory effects of PAF antagonists.
      PAF and the analogs, moreover, desensitized PMN responses to each other but not
      to leukotriene B4 and actually increased (or primed) PMN responses to N-formyl
      MET-LEU-PHE. Finally, 5-hydroxyeicosatetraenoate-enhanced PMN responses to PAF
      and the analogs without enhancing the actions of other stimuli. It
      stereospecifically raised each analog's potency by as much as 100-fold and
      converted a fifth natural analog, 1-alk-1'-enyl-2-acetyl-sn-glycero-3
      phosphoethanolamine from inactive to a weak stimulator of PMN. PAF and its
      analogs thus represent a structurally diverse family of cell-derived
      phospholipids which can activate, prime, and desensitize neutrophils by using a
      common, apparently PAF receptor-dependent mechanism.

PMID- 8280773
TI  - Oxidation and keto reduction of 12-hydroxy-5,8,10,14-eicosatetraenoic acids in
      bovine corneal epithelial microsomes.
AB  - The R and S enantiomers of 12-hydroxyeicosatetraenoic acid (12-HETE) exhibit
      different biological activities. Although they appear to be produced by different
      enzymatic pathways, cytochrome P-450 monooxygenase and lipoxygenase,
      respectively, they display similar metabolism in both corneal epithelium and
      neutrophils. In corneal epithelial microsomes, both enantiomers are subject to
      oxidation and keto reduction reactions to form the dihydro metabolite, 12-hydroxy
      5,8,14-eicosatrienoic acid (12-HETrE), via a keto intermediate. The apparent Km
      for the formation of 12-HETrE was 17.9 and 20 microM for 12(R)-HETE and 12(S)
      HETE, respectively, and the apparent Vmax of the reaction was 17.4 and 8.2
      pmol/mg per min, respectively. Chiral analysis of the dihydro metabolite
      demonstrated a product enantiospecificity. Arachidonic acid, 12(R)-HETE, 12(S)
      HETE and the intermediate of this reaction, 12-oxo-ETrE, were metabolized
      predominantly to 12(R)-HETrE in a ratio [12(R)-HETrE: 12(S)-HETrE] of 7.3:1,
      4.3:1, 1.5:1 and 2.3:1, respectively. 12(R)-HETrE is a potent vasodilator,
      chemotactic and angiogenic factor whose synthesis is induced in inflamed tissues;
      12(S)HETrE is devoid of these properties. 12(R)-HETE, derived from NADPH
      dependent cytochrome P-450 monooxygenases, and 12(S)-HETE, derived from 12
      lipoxygenase, may both play an important role in regulating the inflammatory
      response by serving as substrates for the local synthesis of 12(R)-HETrE.

PMID- 8280774
TI  - Follicular fluid lipoproteins in the mare: evaluation of HDL transfer from plasma
      to follicular fluid.
AB  - Using a density gradient ultracentrifugal procedure, we have separated equine
      plasma and follicular fluid high-density lipoproteins (HDL). The density
      distribution of the follicular fluid HDL was clearly displaced towards the
      highest densities in comparison with that of plasma HDL. Similarly, an analysis
      of size distributions showed a decrease in follicular fluid HDL diameters (4.2 to
      9.2 nm) compared to plasma HDL (5.5 to 9.5 nm). HDL were isolated into three
      subfractions on the basis of the disposition of the Sudan Black stained bands in
      the centrifuge tubes. Concentrations of each subfraction were clearly lower in
      the follicular fluid, and the relative percentages with regard to the plasma
      equivalents were inversely proportional to the molecular weights (23.8% for HDL
      1, 49.9% for HDL-2 and 63.7% for HDL-3). The cholesterol/phospholipid molar ratio
      and the esterified/free cholesterol molar ratio were clearly increased in the
      follicular HDL-2 and HDL-3 subfractions. The apolipoprotein distribution in
      follicular fluid HDL was very close to that in plasma HDL. LCAT activity measured
      in human as well as equine samples was weaker in follicular fluid compared to
      plasma in both species (4.0 nmol of free cholesterol esterified per h per ml vs.
      24 nmol per h per ml). Theoretical concentrations of follicular fluid HDL were
      calculated assuming that the HDL particles would be merely a filtration product
      undergoing no detectable metabolic modifications. Biochemical measurements showed
      that the lightest particles (HDL-1) were less numerous than suggested by the
      theoretical calculation. Thus, although follicular fluid HDL appear to be a
      filtration product of plasma HDL, they undergo metabolic transformations that we
      suggest may be linked to hormonal synthesis and reverse cholesterol transport.

PMID- 8280775
TI  - 1 Acyl-2 acetyl-sn-glycero-3 phosphocholine decreases the susceptibility of low
      density lipoprotein to oxidative modification by copper ions, monocytes or
      endothelial cells.
AB  - The effects of platelet-activating factor (PAF) and its analogue, 1 acyl-2 acetyl
      sn-glycero-3 phosphocholine (1 acyl-2 acetyl-GPC), were investigated on the
      oxidative modification of low-density lipoprotein (LDL) by copper ions, U937
      monocyte-like cells or endothelial cells, by determination of the lipid
      peroxidation end products (TBARS) content and measurement of the electrophoretic
      mobility of the particle. 1 Acyl-2 acetyl-GPC, in the concentration range 1-5
      micrograms/ml, inhibited LDL oxidation in a dose-dependent manner in the three
      systems, whereas PAF had no effect. The protective effect of 1 acyl-2 acetyl-GPC
      was markedly more important when oxidative modification was performed with
      endothelial cells, leading to total inhibition at 5 micrograms/ml. At the same
      concentration, the TBARS production was inhibited by 60% and 20% with monocytes
      and copper ions, respectively. The degradation by J774 macrophage-like cells of
      LDL modified by copper ions, U937 monocyte-like cells or endothelial cells was
      also inhibited when modification was performed in the presence of 1 acyl-2 acetyl
      GPC. Furthermore, preincubation of the LDL particle with 1 acyl-2 acetyl-GPC
      before modification protected the lipoprotein against oxidation, whereas
      preincubation of the cultured cells with the phospholipid had no effect. Thus 1
      acyl-2 acetyl-GPC decreases the susceptibility of the LDL particle to oxidative
      modification, possibly by intercalation within the lipid phase of the particle.
      Since LDL oxidation is believed to play an important role in the initiation and
      progression of atherosclerosis, this inhibitory effect of 1 acyl-2 acetyl-GPC
      might be of importance in view of the fact that this phospholipid is produced
      concomitantly with PAF in some inflammatory cells.

PMID- 8280776
TI  - Digestion of triacylglycerols containing long-chain polyenoic fatty acids in
      vitro by colipase-dependent pancreatic lipase and human milk bile salt-stimulated
      lipase.
AB  - To assess the role of human milk bile salt-stimulated lipase (BSSL) in the
      digestion of polyunsaturated ester bonds of triacylglycerols, hydrolysis of
      docosahexaenoic acid (22:6(n-3)) ester bonds was compared to that of oleic acid
      (18:1(n-9)) or arachidonic acid (20:4(n-6)) esters. As model substrates, we used
      rat chylomicrons obtained after feeding human milk fat globules and radiolabeled
      fatty acids. Radiolabeled chylomicrons were incubated with colipase-dependent
      pancreatic lipase, with BSSL, or with both enzymes in combination. Both enzymes
      hydrolyzed 18:1 more efficiently than 22:6 esters. With colipase-dependent lipase
      there was a large accumulation of 22:6 in diacylglycerol whereas with BSSL it
      accumulated mainly in monoacylglycerol. Esters containing 20:4 were hydrolyzed by
      BSSL as efficiently as 18:1 but this fatty acid also accumulated as
      diacylglycerol with colipase-dependent lipase. At low bile salt concentrations,
      as found in duodenal contents of newborns, colipase-dependent lipase was
      virtually unable to hydrolyze esters of 20:4 and 22:6 whereas BSSL hydrolyzed
      these esters at appreciable rates. Combining the two enzymes gave the most
      efficient hydrolysis of all fatty acids tested regardless of bile salt
      concentrations. BSSL may thus have a physiological role in completing duodenal
      hydrolysis of milk triacylglycerols containing 22:6- or 20:4-esters to free fatty
      acids and monoacylglycerol.

PMID- 8280777
TI  - Evidence that the F2-isoprostane, 8-epi-prostaglandin F2 alpha, is formed in
      vivo.
AB  - F2-isoprostanes are prostaglandin (PG)F2-like compounds that are produced in vivo
      as non-enzymatic products of free radical catalyzed peroxidation of arachidonic
      acid. One F2-isoprostane whose formation should be favored is 8-epi-PGF2 alpha. 8
      Epi-PGF2 alpha has been shown to exert potent bioactivity but proof that it is
      formed in vivo is lacking. Evidence is now presented suggesting that 8-epi-PGF2
      alpha is, in fact, formed in vivo by demonstrating that an endogenous F2
      isoprostane with a retention time on capillary GC identical with that of 8-epi
      PGF2 alpha co-chromatographs through four high resolving HPLC purification
      procedures with authentic radiolabelled 8-epi-PGF2 alpha.

PMID- 8280778
TI  - Hormone-sensitive lipase is closely related to several bacterial proteins, and
      distantly related to acetylcholinesterase and lipoprotein lipase: identification
      of a superfamily of esterases and lipases.
AB  - We have sequenced a gene from Bacillus acidocaldarius which encodes an open
      reading frame (ORF3) of 310 amino acids. The ORF3 was found to be related to the
      mammalian hormone-sensitive lipase (HSL). Searching the protein data base
      revealed five other bacterial proteins related to the HSL. Upon further sequence
      comparisons this HSL-group was found to be related to the family of
      carboxylesterases, and to a family of lipases (lipoprotein, hepatic and
      pancreatic lipases). The evolutionary relationship of these serine-dependent
      hydrolytic enzymes has not been studied previously, and it has not been known
      that these proteins belong to the same superfamily. Finally, the alignment of the
      HSL with the bacterial proteins allowed us to infer the location of the hormone
      sensitive regulatory domain of the HSL-protein.

PMID- 8280779
TI  - Phosphoinositide metabolism, aging and Alzheimer's disease.

PMID- 8280780
TI  - In vitro and in vivo evidence for the role of HDL in reverse cholesterol
      transport.

PMID- 8280781
TI  - Arg-129 plays a specific role in the conformation of antithrombin and in the
      enhancement of factor Xa inhibition by the pentasaccharide sequence of heparin.
AB  - Small amounts of a variant antithrombin (AT) bearing an Arg-129 to Gln mutation
      were purified from plasma by means of affinity chromatography on insolubilized
      heparin at very low ionic strength. As a control, two variant antithrombins, one
      bearing a Pro-41 to Leu mutation and the other an Arg-47 to His mutation, were
      purified in the same way. The biochemical characterization of the variants and
      the kinetic study of thrombin and activated factor X (F Xa) inhibition in the
      presence of heparin and heparin derivatives suggest that Arg-129 plays a specific
      role in AT conformation and F Xa inhibition enhancement. Indeed, the purified
      variant adopted the locked conformation described for AT submitted to mild
      denaturing conditions (Carrell, R.W., Evans, D.Li. and Stein, P.E. (1991) Nature
      353, 576-578) and resembling the latent form of plasminogen activator inhibitor
      (PAI) (Mottonen, J., Strand, A., Symersky, J., Sweet, R.M., Danley, D.E.,
      Geoghegan, K.F., Gerard, R.D. and Goldsmith, E.J. (1992) Nature 355, 270-273).
      Moreover, the mutant AT was partially reactivated by heparin for thrombin
      inhibition, but did not respond to the specific pentasaccharide domain of heparin
      for F Xa inhibition.

PMID- 8280782
TI  - Guanine nucleotide regulatory protein alterations in young Milan hypertensive
      strain rats.
AB  - Vascular smooth muscle cell membranes from prehypertensive rats of the Milan
      hypertensive strain (MHS) were used to examine adenylyl cyclase activity and its
      regulation by guanine nucleotide regulatory proteins (G-proteins). Basal adenylyl
      cyclase activity was similar in MHS and Milan normotensive strain (MNS)
      membranes. Forskolin (10(-4) M) produced a significantly greater stimulatory
      response in MHS membranes, but this was not observed with NaF (10(-2) M).
      Isoproterenol (10(-4) M) caused a significantly decreased stimulation of adenylyl
      cyclase activity in MHS membranes, while prostaglandin E1 (10(-5) M) produced
      similar responses in the two strains. Gi function and GTP responses, as observed
      by biphasic effects of GTP on isoproterenol-stimulated membranes, were similar in
      both strains. The levels of Gi2 alpha and Gq alpha/G11 alpha were similar in the
      two strains, while the levels of Gs alpha (44 and 42 kDa forms) and the beta
      subunit were significantly reduced by approximately 20% in MHS membranes. The
      alpha-subunit of Gi3 was dramatically reduced by approximately 80% in MHS
      membranes. The affinities of beta-adrenergic receptors for the antagonist,
      cyanopindolol, were similar in the two strains; however, the number of beta
      adrenoceptors was substantially reduced in MHS membranes. These findings may be
      of relevance to altered vascular reactivity and transmembrane ion distribution
      observed in the MHS.

PMID- 8280783
TI  - Ferrylmyoglobin formation induced by acute magnesium deficiency in perfused rat
      heart causes cardiac failure.
AB  - The oxidation states of intracellular myoglobin and cytochrome oxidase aa3 were
      monitored by reflectance spectrophotometry in isolated perfused rat hearts
      subjected to an acutely magnesium deficient environment. After exposure to low
      extracellular [Mg2+]o (i.e., 0.3 mM) for 30 min, more than 80% of the
      oxymyoglobin converted to its deoxygenated form. The level of reduced cytochrome
      oxidase aa3 also increased about 80% in low [Mg2+]o. The deoxymyoglobin was
      converted further to a species identified as ferrylmyoglobin by its reaction with
      Na2S to form ferrous sulfmyoglobin which was optically visible. This process, set
      into motion by acute Mg deficiency, resulted from a direct accessibility of the
      exogenous peroxide to the cytosolic protein. The results suggest that a pathway
      leading to cardiac tissue damage, induced by magnesium deficiency, is probably
      involved in the generation of a ferrylmyoglobin radical which could be prevented
      by addition of ascorbate, which is known to be a one-electron reductant of this
      hypervalent form of myoglobin. In further studies, we also investigated whether
      addition of different concentrations of ascorbic acid (AA) to the perfusate could
      enhance myocardial function after exposure to low [Mg2+]o perfusion. Four
      concentrations of AA (0.5, 1, 5, 10 mM) were tested, and the results indicate
      that they exert their effects in a concentration-dependent manner; 1 mM AA was
      the most effective dose in improving aortic output in a Mg-deficient heart.
      Ferrylmyoglobin formation was found to be formed considerably before
      intracellular release of either creatine phosphokinase or lactic dehydrogenase.
      These studies may have wide implications as a new mechanism by which low
      extracellular Mg2+ can induce myocardial injury and subsequent cardiac failure.

PMID- 8280784
TI  - Enhanced cytochrome oxidase activity and modification of lipids in heart
      mitochondria from hyperthyroid rats.
AB  - In order to further investigate the mechanism regulating the control of
      mitochondrial respiration by thyroid hormones, the effect of the hyperthyroidism
      on the kinetic characteristics of cytochrome c oxidase in rat heart mitochondria
      was studied. Mitochondrial preparations from both control and hyperthyroid rats
      had equivalent Km values for cytochrome c, while the maximal activity of
      cytochrome oxidase was significantly increased (by around 30%) in mitochondrial
      preparation from hyperthyroid rats. This enhanced activity of cytochrome oxidase
      was associated to a parallel increase in mitochondrial State 3 respiration. The
      hormone treatment resulted in a decrease in the flux control coefficient of the
      oxidase. The enhanced activity of cytochrome oxidase in hyperthyroid rats does
      not appear to be dependent on an increase in the mass of this enzyme complex in
      that the heme aa3 content was equivalent in both hyperthyroid and control
      preparations. The Arrhenius plot characteristics differ for cytochrome oxidase
      activity in mitochondria from hyperthyroid rats as compared with control rats in
      that the breakpoint of the biphasic plot is shifted to a lower temperature.
      Cardiolipin content was significantly increased in mitochondrial preparations
      from hyperthyroid rats, while there were no significant alterations in the fatty
      acid composition of cardiolipin of control and hyperthyroid preparations. The
      results support the conclusion that the enhanced cytochrome oxidase activity in
      heart mitochondrial preparations from hyperthyroid rats is due to a specific
      increase in the content of cardiolipin.

PMID- 8280785
TI  - Induction of metallothionein by superantigenic bacterial exotoxin: probable
      involvement of the immune system.
AB  - Metallothionein (MT) can be induced in mouse liver by a bacterial exotoxin, toxic
      shock syndrome toxin-1 (TSST-1). Hepatic MT was induced by TSST-1 in a dose
      dependent manner from 100 micrograms/kg through 3 mg/kg in CF-1 mice, and by 6 h
      the induction was almost maximal. The increase of hepatic MT occurred at the mRNA
      level, also, and both MT-I and II mRNAs increased coordinately. Because TSST-1 is
      a superantigen, it was investigated whether TSST-1 induces MT through cytokines
      as a consequence of immunostimulation. In low-cytokine-producing mice (C3H/HeJ),
      up to a dose of 1 mg/kg of TSST-1, there was only 2- to 3-fold increase of
      hepatic MT. In contrast, in normal-cytokine-producing mice (C3Heb/FeJ), TSST-1
      increased MT in a dose-dependent manner, and at a dose of 1 mg/kg, there was a 25
      fold increase in hepatic MT. This suggests that activation of the immune system
      is probably involved in the induction of MT by TSST-1. Studies on the role of
      specific hepatic cytokines (IL-1, TNF-alpha, and IL-6) in TSST-mediated hepatic
      MT induction showed that TSST-1 did not increase hepatic IL-1 or TNF-alpha
      significantly over controls in any of the mouse strains studied. In contrast,
      TSST-1 induced hepatic IL-6 in all three strains of mice. However, in CF-1 and
      C3Heb/FeJ mice (normal-cytokine-producing) IL-6 induction preceded MT mRNA
      induction, but in C3H/HeJ mice (low-cytokine-producing), IL-6 induction did not
      precede MT mRNA induction.

PMID- 8280786
TI  - Hypochlorite oxidation causes cross-linking of Lp(a).
AB  - When purified low density lipoprotein (LDL) or lipoprotein(a) (Lp[a]) was
      oxidized in vitro using concentrations of hypochlorite (50-500 microM) which
      might be achieved by activated neutrophils in vivo, high molecular weight species
      were observed on SDS polyacrylamide gels. The reaction was concentration-,
      temperature- and time-dependent. The high molecular weight apoprotein complexes
      were resistant to heating in SDS and DTT, suggesting covalent, but non-disulfide
      bond, cross-linking. Negligible amounts of lower molecular weight degradation
      products were formed. Bityrosine formation, measured by fluorescence and HPLC
      analysis, was found to increase with the amount of hypochlorite added. However,
      the molar concentration of bityrosine could not account for cross-linking, even
      if it was assumed that every bityrosine was intermolecular. Hypochlorite-oxidized
      Lp(a) and LDL were both effective as ligands for loading mouse peritoneal
      macrophages in vitro. We conclude that hypochlorite produced in inflammatory
      reactions might be important in the generation of atherogenic forms of
      lipoproteins.

PMID- 8280787
TI  - Screening for ferrochelatase mutations: molecular heterogeneity of erythropoietic
      protoporphyria.
AB  - The DNA of 21 patients from 19 unrelated families with erythropoietic
      protoporphyria (EPP) were screened for the 6 ferrochelatase point mutations so
      far described. The mutation previously described by us (A >> T transversion at
      position -3 of the donor site of intron 10, causing exon 10 skipping) was
      detected in two additional unrelated EPP patients: in these patients, cDNA
      lacking exon 10 was also detected. The mutation described by Nakahashi et al. as
      responsible for exon 2 skipping (C >> T transition at position -23 of the
      acceptor site of intron 1), although also observed in some normal individuals,
      was invariably observed in all EPP patients tested and may thus play some role in
      the pathogenesis of EPP. Thus, it does not appear that this mutation is the
      primary mechanism underlying exon 2 skipping. None of the other four previously
      described mutations were detected. These data demonstrate the heterogeneity of
      the ferrochelatase locus and of the genetic defect in EPP.

PMID- 8280788
TI  - Glycolysis and glucose oxidation during reperfusion of ischemic hearts from
      diabetic rats.
AB  - Stimulation of glucose oxidation by dichloroacetate (DCA) treatment is beneficial
      during recovery of ischemic hearts from non-diabetic rats. We therefore
      determined whether DCA treatment of diabetic rat hearts (in which glucose use is
      extremely low), increases recovery of function of hearts reperfused following
      ischemia. Isolated working hearts from 6 week streptozotocin-diabetic rats were
      perfused with 11 mM [2-3H/U-14C]glucose, 1.2 mM palmitate, 20 microU/ml insulin,
      and subjected to 30 min of no flow ischemia followed by 60 min reperfusion. Heart
      function (expressed as the product of heart rate and peak systolic pressure),
      prior to ischemia, was depressed in diabetic hearts compared to controls (HR x
      PSP x 10(-3) was 18.2 +/- 1 and 24.3 +/- 1 beats/mm Hg/min in diabetic and
      control hearts respectively) but recovered to pre-ischemic levels following
      ischemia, whereas recovery of control hearts was significantly decreased (17.8 +/
      1 and 11.9 +/- 3 beats/mm Hg/min in diabetic and control hearts respectively).
      This enhanced recovery of diabetic rat hearts occurred even though glucose
      oxidation during reperfusion was significantly reduced as compared to controls
      (39 +/- 6 and 208 +/- 42 nmol/min/g dry wt, in diabetic and control hearts
      respectively). Glycolytic rates (3H2O production) during reperfusion were similar
      in diabetic and control hearts (1623 +/- 359 and 2071 +/- 288 nmol/min/g dry wt,
      respectively). If DCA (1 mM) was added at reperfusion, hearts from control
      animals exhibited a significant improvement in function (HR x PSP x 10(-3)
      recovered to 20 +/- 4 beats/mm Hg/min) that was accompanied by a 4-fold increase
      in glucose oxidation (from 208 +/- 42 to 753 +/- 111 nmol/min/g dry wt). DCA was
      without effect on functional recovery of diabetic rat hearts during reperfusion
      but did significantly increase glucose oxidation from 39 +/- 6 to 179 +/- 44
      nmol/min/g dry wt). These data suggest that, unlike control hearts, low glucose
      oxidation rates are not an important factor in reperfusion recovery of previously
      ischemic diabetic rat hearts.

PMID- 8280789
TI  - Increased oxidizability of plasma low density lipoprotein from patients with
      coronary artery disease.
AB  - Oxidative modification of lipoproteins may play a crucial role in the
      pathogenesis of atherosclerosis. This study was designed to examine whether
      increased lipid peroxides and/or oxidative susceptibility of plasma lipoproteins
      occur in patients with coronary artery disease. The levels of lipid peroxides,
      estimated as thiobarbituric acid-reactive substances (TBARS), were significantly
      greater in the plasma and very low density lipoprotein (VLDL) of symptomatic
      patients with coronary artery disease than in those of healthy persons, but the
      TBARS levels of low density lipoprotein (LDL) and high density lipoprotein (HDL)
      showed insignificant difference between patients and normals. To evaluate the
      oxidative susceptibility of lipoproteins, we employed in vitro Cu2+ oxidation of
      lipoproteins monitored by changes in fluorescence, TBARS level, trinitrobenzene
      sulfonic acid (TNBS) reactivity, apolipoprotein immunoreactivity and agarose gel
      electrophoretic mobility. While pooled VLDL and LDL of normal controls were
      oxidized at 5-10 microM Cu2+, pooled VLDL and LDL of patients with coronary
      artery disease were oxidized at 1-2.5 microM Cu2+, i.e., at relatively lower
      oxidative stress. At 5 microM Cu2+, VLDL and LDL of patients with coronary artery
      disease still showed a faster oxidation rate, judged by the rate of fluorescence
      increase, higher TBARS level, less TNBS reactivity, greater change in apo B
      immunoreactivity and higher electrophoretic mobility than those of normal
      controls. However, the difference on the oxidizability of HDL was insignificant
      for patients vs. normals. In conclusion, we have shown that plasma VLDL and LDL
      of patients with coronary artery disease are more susceptible to in vitro
      oxidative modification than those of healthy persons. The data suggest that
      enhanced oxidizability of plasma lipoproteins may be an important factor
      influencing the development of coronary artery disease.

PMID- 8280790
TI  - Effect of liposomally encapsulated MTX-DMPE conjugates upon TNF alpha and PGE2
      release by lipopolysaccharide stimulated rat peritoneal macrophages.
AB  - The ability of liposomally encapsulated preparations of methotrexate (MTX) and
      three of its lipophilic derivatives (MTX-gamma-DMPE, MTX-alpha-DMPE and MTX
      alpha,gamma-diDMPE) to alter mediator release by lipopolysaccharide (LPS)
      stimulated rat peritoneal macrophages (PM theta) was investigated. The viability
      of these macrophages when incubated with approximately 6.0 nmol/10(5) cells of
      the respective liposomal preparations (MTX-LIPO, MTX-gamma-LIPO, MTX-alpha-LIPO
      and MTX-di-LIPO) for 20 h was greater than 80%. Treatment of macrophages, which
      had been incubated with MTX-alpha-LIPO (5.5 nmol/10(5) cells), MTX-gamma-LIPO
      (6.9 nmol/10(5) cells) and MTX-di-LIPO (4.5 nmol/10(5) cells) for 20 h, with
      antibody-coated sheep red blood cells resulted in 105 +/- 9.6%, 80.6 +/- 5.6% and
      91 +/- 11.4% phagocytosis respectively (mean +/- S.E.M.). At similar
      concentrations of MTX-alpha-LIPO, MTX-gamma-LIPO and MTX-di-LIPO (6.5 nmol/10(5)
      cells), PGE2 release from LPS-stimulated rat peritoneal macrophages was inhibited
      by 85.3 +/- 3.7%, 68.7 +/- 0.6% and 88.8 +/- 2.2%, respectively (mean +/- S.E.M.,
      n = 4). Incubation of these macrophages with 12, 10 and 9.4 nmol/10(5) cells of
      the respective liposomal preparations resulted in 89 +/- 3.3%, 62 +/- 5.5% and 85
      +/- 3.9% inhibition of TNF alpha release (mean +/- S.E.M., n = 4). However, at
      this concentration MTX-di-LIPO was toxic. Neither MTX (20-2.5 nmol/10(5) cells)
      nor MTX-LIPO (5.6 nmol/10(5) cells) affected TNF alpha release from LPS
      stimulated macrophages. Whilst free MTX was also ineffective at inhibiting PGE2
      from these cells, incubation with MTX-LIPO at the above concentration resulted in
      76.9 +/- 2.6% inhibition of the prostaglandins release.

PMID- 8280791
TI  - Isoenzyme-specific quantitative immunoassays for cytosolic glutathione
      transferases and measurement of the enzymes in blood plasma from cancer patients
      and in tumor cell lines.
AB  - Enzyme-linked immunoassays (ELISAs) based on the double-antibody sandwich
      technique have been developed for the quantitative analysis of the major human
      cytosolic class Pi, Mu and Alpha glutathione transferases (GSTs). The procedures
      were optimized with respect to antibody concentration for coating of plates as
      well as other parameters in order to achieve high sensitivity and accuracy. No
      cross-reactivity was detected between members of the three different classes of
      GSTs or among the Mu class GSTs M2-2, M3-3 and M4-4 with the ELISA for GST M1-1.
      The ELISAs have been applied to establish the cytosolic GST profiles of 10 cell
      lines and to monitor the plasma GST levels in cancer patients. The results
      revealed that the class Pi GST was the dominant isoenzyme in six (LS 174T, HCT-8,
      Hu 549 Pat, K-562, U-937 and Hu 549) out of nine tumor cell lines and
      immortalized hepatocytes (Chang Liver). The isoenzymes A1-1 and M1-1 were
      determined to be the major GST components in Hep G2 and HeLa cells, respectively.
      In a clinical study, the majority of the patients with urinary bladder cancer
      were found to have increased plasma levels of both GST A1-1 and GST P1-1 (10/15),
      while patients with renal cancer frequently showed increases only in GST P1-1
      (5/8). The results demonstrate that the ELISAs are suitable for analyzing GST
      phenotypes in both normal and tumor cells and in monitoring plasma levels of GSTs
      in cancer patients.

PMID- 8280792
TI  - Effect of endotoxin on lipid order and motion in erythrocyte membranes.
AB  - Electron paramagnetic resonance employing a lipid-specific spin label has been
      used to investigate the molecular effects of endotoxin on the physical state of
      bilayer lipids in rat erythrocyte membranes. When added at a concentration as low
      as 40 micrograms/ml to whole blood (plasma plus leukocytes present), decreased
      membrane lipid motion was found in subsequently washed and spin-labeled intact
      erythrocytes (P < 0.02). However, if endotoxin were added to washed, plasma plus
      leukocyte-free intact erythrocytes, no change in the motion of the spin label was
      found, suggesting that plasma-soluble substances and/or leukocytes are required
      to produce the change in the physical state of lipids. The decreased lipid motion
      found in these studies is discussed with reference to the known decreased
      deformability of endotoxin-treated red cells and to the pathogenesis of sepsis.

PMID- 8280793
TI  - Musings on the struggle--Part IV: Aftermath of the RAC meeting.

PMID- 8280794
TI  - Efficient episomal expression vector for human transitional carcinoma cells.
AB  - To develop an efficient expression vector for human transitional carcinoma cells,
      we evaluated the replication activity of episomal vectors derived from the BK
      virus (BKV) and the Epstein-Barr virus (EBV) in HT-1376 bladder carcinoma cells.
      Southern blot analysis of transient transfectants indicated that the BKV-derived
      episome replicated extrachromosomally whereas the EBV replicon did not appear to
      be functional in these cells. HT-1376 cells were stably transfected with BKV
      derived episomes containing the neomycin resistance gene as a selectable marker.
      Southern analysis demonstrated that these stable transfectants contained
      approximately 150 copies of the BKV episome per cell. There was no evidence of
      integration of the BKV episome into genomic DNA following selection with G418 for
      10 weeks. These stable episomal transfectants had approximately 20-fold higher
      levels of expression of neomycin resistance gene mRNA than clones of HT-1376
      cells transfected with pSV2NEO which contained five integrated copies of this
      gene. In soft agar cloning experiments, BKV episomes were efficiently transferred
      to the progeny of these transfectants during cell division over multiple
      generations. Additionally, BKV episomal copy number is maintained in stable
      transfectants after withdrawal of selection pressure for over 2 months. These
      data demonstrate that BKV-derived episomes replicate efficiently in bladder
      carcinoma cells, yielding stable transfectants having a high episomal copy number
      and expressing encoded genes at high levels. BKV-derived episomes may be useful
      in gene therapy strategies to modulate the growth of bladder carcinoma cells.

PMID- 8280795
TI  - Development of methods for somatic cell gene therapy directed against viral
      diseases, using retroviral vectors carrying the murine or human interferon-beta
      coding sequence: establishment of the antiviral state in human cells.
AB  - We are developing methods for somatic cell gene therapy directed against chronic
      and fatal virus infections, such as acquired immunodeficiency (AIDS), by
      transforming cells with a constitutively expressed interferon (IFN) coding
      sequence. Previous work from our laboratory has shown that stable antiviral
      expression (SAVE) can be obtained in murine BALB/c 3T3 cells and human U937 cells
      transformed with plasmids carrying either the murine or the human IFN-beta coding
      sequence placed under the expression control of a 0.6-kb Xho II-Nru I promoter
      region of the murine H-2Kb major histocompatibility complex (MHC) gene (Mace et
      al., 1991; Seif et al., 1991). In the present paper, we report the construction
      of murine (Mu) and human (Hu) IFN-beta-expressing retroviral vectors (pMPZen
      MuIFN beta, pHMB-KbMuIFN beta) and the problems encountered. Because of the
      murine origin of commonly used packaging cells and the species specificity of
      IFN, it was evident that placing the murine IFN-beta sequence under constitutive
      expression control could result in the production of Mu IFN in the murine
      packaging system, and thereby lead to decreased vector production and also to
      enhanced resistance of target cells. Using a packaging cell line that releases a
      beta-galactosidase-expressing vector, we show that, as expected, Mu IFN
      alpha/beta decreases vector production of murine packaging cells and also
      inhibits the transformation of target NIH-3T3 cells with this vector, but the
      presence of anti-Mu IFN antibodies rescues the viral titer of the packaging cells
      and restores the sensitivity of target cells to virus transformation. However,
      the same antibody treatment is unable to rescue the viral titer of psi-2
      packaging cells producing autocrine Mu IFN-beta encoded by the pMPZen-MuIFN beta
      and pHMB-KbMuIFN beta vectors. Because of the species specificity of IFN, this
      problem is circumvented with the pMFG-HuIFN beta vector carrying the human IFN
      beta sequence. In spite of the production of Hu IFN, murine psi-CRIP packaging
      cells are able to release retroviral vectors expressing Hu IFN-beta, and these
      amphotropic vectors can transform human MRC-5 cells and confer to these cells an
      enhanced resistance to vesicular stomatitis virus (VSV) infection.

PMID- 8280796
TI  - Infection of human cells with murine amphotropic replication-competent
      retroviruses.
AB  - Replication of the murine wild-type 4070A amphotropic retrovirus and a
      recombinant amphotropic replication-competent retrovirus arising from the PA12
      packaging cell line varied considerably among the primate cell types tested.
      Medium from infected primate fibroblasts and endothelial cells contained the
      highest viral titers [10(4)-10(5) focus-forming units (ffu)/ml], while most
      hematopoietic cell lines, such as K562 and MOLT4, were associated with viral
      titers in the range of 10(3)-10(4) ffu/ml. Interestingly, HTLV-1-transformed T
      cell lines (TJF-2 and HM) and primary tumor infiltrating lymphocytes (TIL) had
      very low viral titer (0-10(1) ffu/ml). The low production of virus was not due to
      low infectivity and, in contrast to the virus, retroviral vectors were expressed
      without difficulty. Because screening for replication-competent retrovirus (RCR)
      is an important component of human retroviral-mediated gene therapy clinical
      protocols, a variety of assays were tested for their ability to detect RCR in
      virus-exposed cell lines. A biologic assay (3T3 amplification) and polymerase
      chain reaction (PCR) for the 4070A viral envelope are effective screening methods
      for RCR, even in cell lines associated with low virus production.

PMID- 8280797
TI  - Retrovirally transduced Escherichia coli gpt genes combine selectability with
      chemosensitivity capable of mediating tumor eradication.
AB  - "Suicide genes" encoding exceptional sensitivity to chemotherapeutic agents can
      potentially improve the selectivity of cancer therapy. As a component of a
      retroviral gene therapy vector, a suicide gene might also improve the safety of
      gene therapy by permitting the subsequent ablation of transduced cells exhibiting
      neoplastic or other aberrant behavior. An extra gene, however, cannot easily be
      added to vectors already carrying a therapeutic gene and a selectable drug
      resistance marker without compromising gene expression. To circumvent this
      obstacle, we have investigated a retrovirally transduced Escherichia coli gpt
      gene on the basis of evidence that it might subserve a dual
      sensitivity/resistance function. A gpt vector was used to transduce the gene into
      murine K3T3 sarcoma cells. In vitro, gpt-positive K3T3 clones could be selected
      on the basis of resistance to a regimen containing mycophenolic acid and
      xanthine; the same clones were 18 to 86 times as sensitive to 6-thioxanthine
      (6TX) as their gpt-negative counterparts. In mice, systemic 6TX therapy induced
      durable regressions in 19/20 gpt-positive K3T3 sarcomas without affecting gpt
      negative tumors. These results indicate that selectability and in vivo
      chemosensitivity can be expressed in the same cell population from a single
      retrovirally transduced gene and imply the additional possibility of fusing the
      gpt gene with a therapeutic gene to create vectors expressing three important
      functions from a single gene.

PMID- 8280798
TI  - Widespread distribution of cells containing human DNA in embryos derived from
      mouse eggs injected with human chromosome fragments.
AB  - The possibility that metaphase chromosomes can serve as a source of genetic
      material for making transgenic mice was suggested by our previous finding of the
      incorporation of human satellite DNA into mouse embryos that were injected with
      microdissected human centromeric fragments. In the present study, we further
      examined whether this chromosome transfer method can be used to generate
      transgenic mice containing a portion of human chromosome 4 spanning the
      Huntington's disease (HD) gene. For this purpose, we used an improved method of
      metaphase chromosome preparation that may minimize the potential for DNA damage.
      Using metaphase chromosomes prepared in this manner, chromosome fragments
      spanning the region of chromosome 4 containing the HD gene were microdissected,
      retrieved, and injected into fertilized mouse eggs. The injected eggs exhibited
      good viability and developed with a high efficiency when implanted into foster
      mothers. To determine whether the human DNA from the injected chromosome fragment
      had been incorporated into the mouse genome, embryos were harvested at 12.5 days
      of gestation (dg) and analyzed by in situ hybridization using a human Alu
      repetitive DNA probe. This analysis showed that most of the embryos contained
      cells with human Alu repeats. However, all of the embryos were mosaic, and the
      level of mosaicism was such that we were not able to determine the precise
      chromosomal origin of the human DNA insert. We discuss the possible basis for the
      mosaicism and the potential value of such mosaic animals for studying
      Huntington's disease.

PMID- 8280799
TI  - Stable expression of the wild-type p53 gene in human lung cancer cells after
      retrovirus-mediated gene transfer.
AB  - A retroviral vector-mediated system was established to allow efficient
      transduction of the wild-type p53 gene into human lung cancer cell lines H358a
      (deleted p53) and H322a (mutant p53). LNSX/p53 constructs incorporating p53 cDNA
      driven by a beta-actin promoter mediated stable integration of p53. p53 mRNA and
      protein were detected in these cell lines 6 months after transduction by Northern
      and Western blot analyses. Restoration of the wild-type p53 gene suppressed
      growth in the two transduced cell lines but had no effect in another transduced
      tumor cell line, H460a, which has an endogenous wild-type p53 gene. A high
      transduction efficiency was obtained in cell lines H460a, H322a, and H358a after
      five cycles of transduction in vitro. Mixing experiments showed that transduced
      cells could reduce the growth rate of nontransduced cells; this reduction may
      have been mediated by factors shed into the supernatant of the transduced cell
      cultures.

PMID- 8280800
TI  - The development and testing of retroviral vectors expressing trans-dominant
      mutants of HIV-1 proteins to confer anti-HIV-1 resistance.
AB  - Trans-dominant mutants of human immunodeficiency virus type 1 (HIV-1) Tat and Rev
      are attractive candidates for use in gene therapy in the treatment of HIV-1
      infections because both are essential for viral replication. Retroviral vectors
      were constructed to allow either Tat-inducible or Tat- and Rev-inducible
      expression of trans-dominant mutants of Tat and Rev. These vectors were used to
      infect a human CD4+ lymphocyte-derived cell line, MT4. To determine the efficacy
      of various Tat and Rev mutants in inhibiting HIV-1 multiplication, MT4 cells
      containing mutant-expressing constructs were infected with HIV-1, and the amount
      of HIV-1 released in the culture medium was measured for up to 30 days. A high
      level of resistance was observed in cells expressing the double tat/rev mutant in
      a Tat-inducible manner.

PMID- 8280801
TI  - NIDDK symposium on the impact of molecular genetics on the treatment of genetic
      diseases.

PMID- 8280802
TI  - The safety of retroviral vectors.

PMID- 8280803
TI  - A study of the safety and survival of the adoptive transfer of genetically marked
      syngeneic lymphocytes in HIV-infected identical twins.
AB  - This phase I/II pilot project will evaluate the survival, tolerance, safety, and
      efficacy of infusions of activated, gene marked, syngeneic T lymphocytes obtained
      from HIV seronegative identical twins on the functional immune status of HIV
      infected twin recipients. T cells from each seronegative twin will be obtained by
      periodic apheresis, separated into CD4 and CD8 enriched populations by monoclonal
      antibody affinity binding techniques, induced to polyclonal proliferation with
      anti-CD3 and rIL-2 stimulation, transduced with distinctive neoR retroviral
      vectors, and expanded 10-1,000 fold in numbers during approximately 2 weeks of
      culture. These marked T cell fractions will then be infused into the seropositive
      twins and the survival of the uniquely marked T cell populations will be
      monitored by vector-specific PCR, while the recipients' functional immune status
      is monitored by standard in vitro and in vivo testing protocols. A total of 3
      cycles of treatment will be given at intervals of 6 weeks between infusions.

PMID- 8280804
TI  - [The glycemic response to a test breakfast of an enteral diet with fiber and a
      high starch content in diabetics treated with insulin and oral antidiabetics].
AB  - An enteral nutrition preparation appeared recently on the Spanish market
      specifically for diabetic patients. It is a normocaloric and normoproteic formula
      of low osmolarity, rich in soluble fibre and slow-absorption carbohydrates such
      as fructose and starch, following the classic norms of the American Diabetics
      Association. The glycemic response was examined at 0, 30, 60 and 120 minutes
      following the ingestion of 250 cc of Precitene Diabet as breakfast for 40
      diabetic patients, half treated with oral antidiabetic substances (DMado) and the
      other half with insulin (DMins). In both groups, the greatest glycemic increase
      was at 60 minutes. In the DMado patients, the increase at 60 minutes (70 mg/dl)
      was not significantly different from that considered by Skyler as acceptable. The
      same occurred at 120 minutes (40 mg/dl). In the DMins patients, the glycemic
      increase at 60 minutes was 27 +/- 29 mg/dl, more than that considered acceptable
      by Skyler (p 0.0006). After 120 minutes this difference was also greater than the
      acceptable level, by 41 +/- 38 mg/dl (p 0.0002). In conclusion, it may be
      considered that, for DMado patients, glycemic control remains within the
      postprandial limits considered to be "acceptable" so that no treatment
      modification is felt necessary in the administration of enteral nutrition with
      Precitene Diabet. The glycemic response in the DMins patients was higher than
      "acceptable", calling for rapid insulin supplements to their habitual NPH insulin
      doses.

PMID- 8280805
TI  - Effects of xylitol on carbohydrate and protein metabolism after trauma and during
      sepsis.
AB  - INTRODUCTION: Total parenteral nutrition (TPN) after trauma and during sepsis has
      two major goals. One is the reduction of increased protein catabolism, the second
      is to avoid hyperglycemia and enhanced hepatic gluconeogenesis. Glucose and
      xylitol differ in their utilization rates after trauma and during sepsis. Whole
      body glucose utilization is reduced during such states, while the utilization of
      xylitol is more than doubled. In order to investigate whether these differences
      are associated with beneficial effects on hepatic glucose production and protein
      sparing, we conducted two animal and two clinical studies. METHODS: For the
      analysis of glucose and protein turnover radioactive and stable isotope
      techniques were applied. In burned rats primed constant infusions of 6-[3H]
      glucose, 1-[14C]-alanine, 3-[14C]-alanine and U-[14C]-acetate were used to
      determine whole body glucose turnover, gluconeogenesis from C3-precursors and
      alanine flux. In septic rats nitrogen balance was calculated after determination
      of 24-hour-urine nitrogen content measured by micro-Kjeldahl digestion. 24-hour
      urinary 3-methyl-histidine excretion was analysed by amino acid autoanalyser. In
      human studies hepatic glucose production and urea synthesis rates were measured
      using primed continuous infusions of [6,6-d2]-glucose and [2-N15]-urea,
      respectively. RESULTS: In the first trauma model we demonstrated that hypocaloric
      xylitol in contrast to glucose significantly reduced hepatic glucose production
      and gluconeogenesis from C3-carbons. In the septic rat exchange of glucose
      calories by xylitol in a proportion of 1:1 was associated with a significantly
      ameliorated nitrogen retention and lower 3-methyl-histidine excretion. In two
      studies on surgical intensive care patients we were able to confirm these
      nitrogen sparing properties of xylitol. Hepatic glucose production and urea
      synthesis rates were significantly reduced during xylitol infusion after trauma,
      whereas equicaloric glucose had no effects. In septic patients xylitol led to
      significant lower lactate concentrations and gluconeogenesis rates than
      isocaloric glucose. DISCUSSION: In animal as well as in human studies hypocaloric
      xylitol and the mixture of glucose/xylitol (1:1) were more efficient in
      preserving body protein than glucose alone. Hepatic gluconeogenesis was
      significantly reduced when compared to isocaloric glucose. During the acute phase
      after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg BW/d
      by xylitol. During long-term TPN a glucose/xylitol mixture (1:1) in a dosage of 6
      g/kg BW/d is recommended together with amino acids and, if necessary, lipids.

PMID- 8280806
TI  - [The stability of antibiotics administered in "and" with a parenteral nutrition
      mixture enriched with branched-chain amino acids. II. The cephalosporins].
AB  - Part I of these stability studies commented on the benefits, in terms of care and
      therapy, of the Y administration of antibiotics and parenteral nutrition. The aim
      of this study is to determine the stability of the cephalosporins ceftazidime,
      ceftriaxone, ceftizosime and cefotaxime in vitro, at therapeutic concentrations,
      infused together with a parenteral nutrition mixture with polyols, enriched in
      branched chained amino acids, and without lipids. A microbiological stability
      analysis was carried out on the antibiotics in the parenteral nutrition, and an
      HPLC aminogram was done to determine the concentration of amino acids in the
      infusion together with the antibiotic. As well, pH, osmolarity and colour change
      were measured in the antibiotics, in the parenteral nutrition used and in the
      joint infusion mixtures. It is concluded that parenteral nutrition can be jointly
      infused with cefotaxime and ceftazidime, at the concentrations studied, given the
      stability results obtained both with HPLC (antibiotics and amino acids) and
      microbiologically (antibiotics). At the same time, the microbiological analysis
      of ceftriaxone with the nutrition showed its stability in the study conditions.
      Its joint infusion with parenteral nutrition, studied by HPLC, confirmed the
      stability of the amino acids. The ceftizoxime analysed by HPLC remained stable
      during joint infusion with the parenteral nutrition.

PMID- 8280807
TI  - ["Nutrition": a program to facilitate the calculations of the composition of
      menus and diets].
AB  - The methodology used to build a software program to compute the nutrient
      composition of menus and diets is discussed. Topics as the variability of food
      composition, the scarcity of local food composition data, the bias that may be
      incurred in nutrient data of food consumption studies are extensively discussed
      and also the possible solution through the software program. All of these topics
      must be taken into account in epidemiological studies as well as in computing
      diet composition.

PMID- 8280808
TI  - [The limits of the Nutrition Committee in applying parenteral nutrition].
AB  - In order to assess the benefits of a Nutritional Team in our hospital, the
      Nutritional Committee made a prospective study concerning the Parenteral
      Nutrition application between June 8th and July 23rd 1992. We studied 94
      patients, mean age 51.5 (0-88). They had 918 nutritional units (20 NU/day) for a
      mean time of 13.2 days. The main nutritional indication was intestinal pathology
      (47.9% onco-surgical patients). A Parenteral Nutrition standard type was usually
      given to patients through a Drum type catheter. Infectious complications reached
      a 38.5% (13.8% thrombophlebitis). We have performed analytical controls in 83.7%
      patients, 83.6% of them had pathologic results. The percentage was of deaths
      7.5%. After these results, we conclude that there is a need for a specifically
      trained medical group taking care of the nutritional management of the patients.
      Thus, we could assure the quality of nutritional therapy.

PMID- 8280809
TI  - [An analysis of the reliability of 2 types of enteral nutrition pumps].
AB  - The main advantages of infusion pumps are their enhanced accuracy and safety in
      providing enteral nutrition. We proposed to observe pumps reliability in
      connection with a variety of factors such as the type of pump used, the
      administration rate and the energy density of the diets used. An experimental
      design was prepared with two types of enteral nutrition pumps-VP, volumetric
      pump, and PP, peristaltic pump. The clinical simulation was done by connecting
      the enteral nutrition equipment to a graduated dosing system, making hourly
      measurements of the volume infused. The Reliability Index (RI) used was the ratio
      between the volume infused by the pump and the regulated dose (Vi/Do). Five
      volumetric pumps (FLEXIFLO COMPANION) and five peristaltic pumps (FLEXIFLO II)
      were selected at random from a single commercial outlet. Each was used for twenty
      three hours, without interruption, to infuse five types of diet with different
      energy densities (D1:2 Kcal/ml, D2: 1.5 Kcal/ml, D3: 1.25 Kcal/ml, D4: diet with
      fibre, and D5: reconstituted powder diet) at three different flow rates (40, 80
      and 120 ml/h), to provide fifteen experimental conditions with each pump.
      Reliability was maintained for both types of pump within the margin of error
      claimed by the manufacturer (+/- 10%) except in the first hour of infusion (RI =
      71.4%). Comparison of the overall RI between the two pump types revealed
      significant differences, with an RI below the reference range for the VP only
      during hour 23 (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280810
TI  - [The variability of the Harris-Benedict equation (or, if you copy from something
      copied, you can come off badly)].

PMID- 8280811
TI  - Inactivation of viruses in fresh-frozen plasma.
AB  - Methylene blue (MB) or solvent/detergent (SD) treatment is used for the
      inactivation of lipid-enveloped viruses in plasma. One important characteristic
      of the SD treatment is the necessity to pool plasma from different donors, thus
      inducing the risk of spreading infectious particles. MB treatment can be applied
      to single-donor plasma, causing no greater infectious risk than conventional
      fresh-frozen plasma (FFP). However, the virucidal efficacy of the SD method
      regarding HIV, HBV and HCV has been significantly better examined and proven than
      the MB treatment. Most of the therapeutic constituents of both plasma products
      are well maintained; coagulation factors decrease by roughly 5-20%. SD treatment
      reduces protein S and alpha 2-antiplasmin by approximately 40%, whereas MB
      treatment leads to a significant photooxidative alteration of fibrinogen with a
      disturbance of fibrin polymerization. As current studies show, the use of either
      plasma product is obviously not limited by acute or chronic toxicity. Several
      studies are in progress to evaluate the relevance of alterations in FFP quality
      which may affect the clinical efficacy of virus-inactivated plasma.

PMID- 8280812
TI  - TGF-beta 1 inhibits polyamine biosynthesis in K 562 leukemic cells.
AB  - The present study proved that TGF-beta 1 significantly inhibited the growth of K
      562 cells. The drop in cell numbers after 24 h incubation with increasing
      concentrations of TGF-beta 1 (0.01, 0.1, 1.0, 10.0 ng/ml) was accompanied by
      significant suppression of the activity of two key enzymes of polyamine
      biosynthesis: ornithine decarboxylase (ODC) and S-adenosylmethionine
      decarboxylase (SAMDC). In contrast to ODC and SAMDC activity, TGF-beta 1 did not
      significantly affect the absolute concentration of spermidine and spermine in K
      562 cells. We suppose that the lack of an evident drop in concentration of
      spermidine and spermine in spite of a significant decrease in ODC and SAMDC
      activity in K 562 cells exposed to TGF-beta 1 resulted from the uptake of
      polyamines from the extracellular space.

PMID- 8280813
TI  - Reduction of HTLV-I-infected cells in blood by leukocyte filtration.
AB  - Leukocyte filtration was performed with HTLV-I-infected blood and with blood
      supplemented with cultured HTLV-I-transformed cells. Reduction of infectivity
      upon leukocyte filtration was determined by the polymerase chain reaction (PCR)
      using primers indicative for the HTLV-I-pol and tax genes. Two different
      commercially available filters were used: a column-shaped cellulose acetate and a
      flat-bed polyester filter. Both filters yielded reduction of at least 3 10logs
      for cultured HTLV-I-infected cells. When blood from HTLV-I-infected individuals
      was used for filtration, the number of infected cells was reduced by 1-3 10logs.
      Although filtered blood as yet cannot be regarded as safe, it is concluded that
      leukocyte filtration of HTLV-I-infected blood potentially contributes to reducing
      the spread of HTLV-I by blood transfusion.

PMID- 8280814
TI  - Interstitial lung disease--an underdiagnosed side effect of chlorambucil?
AB  - A case of recurrent interstitial pneumonia following re-exposure to chlorambucil
      therapy for chronic lymphocytic leukemia is presented. Chlorambucil is a rare
      cause of pulmonary disease. The onset of symptoms may occur after only some weeks
      or after up to several years with no dose-response relationship. Therapy involves
      the discontinuation of the offending drug and the administration of steroids. The
      prognosis is poor, with a mortality greater than 50%.

PMID- 8280815
TI  - Acquired factor VIII inhibitor preceding chronic lymphocytic leukemia.
AB  - An acquired factor VIII inhibitor was found in an 82-year-old woman who presented
      with numerous spontaneously appearing ecchymoses. Coagulation studies revealed
      the presence of a prolonged activated partial thromboplastin time that was not
      corrected by 1:1 mixture with normal fresh plasma after a 2-h incubation. Factor
      VIII:C was 4%, and the titer for factor VIII inhibitor was 9 Bethesda units.
      Three months later, after a retroperitoneal hemorrhage, a lymphocytosis was found
      in her peripheral blood with morphological and surface immunophenotype
      characteristics of B-cell chronic lymphocytic leukemia, later confirmed by bone
      marrow morphological and immunocytochemical examinations. To our knowledge, this
      is the first report of an autoimmune factor VIII inhibitor associated with
      chronic lymphocytic leukemia.

PMID- 8280816
TI  - Review article: drug-induced hepatotoxicity.
AB  - The liver is central to the metabolic disposition of virtually all drugs and
      xenobiotics (foreign substances). For the most part, this process is accomplished
      without injury to the liver itself or to other organs. A few compounds such as
      acetaminophen, CCl4 and the toxin responsible for mushroom poisoning are toxic
      themselves or produce metabolites which cause liver injury in a uniform, dose
      dependent fashion. However, most agents form a sufficiently toxic byproduct and
      cause liver injury only quite rarely, under special circumstances. Generation of
      a toxic metabolite within the hepatocyte may produce direct cell injury with
      disruption of intracellular function, or may cause indirect injury by immune
      mediated membrane damage. Factors promoting the accumulation of toxins include
      genetic enzyme variants which allow greater formation of the harmful metabolite,
      induction of an isozyme species which produces more than the usual quantity of
      the toxin, interference with regular (non-toxic) metabolic pathways by substrate
      competition for enzyme, or depletion of required detoxifying substrates. The
      following review will provide clinical examples of some of these well-known
      metabolic reactions, discuss some new issues in drug-induced hepatotoxicity, such
      as use of combination agents and complex multiple drug regimens, alternative
      health strategies (vitamins and herbal remedies) as well as the widespread use of
      cocaine. The overall message is that, as new compounds are issued, new
      opportunities for drug-induced hepatotoxicity arise. Until extensive experience
      with any new compound has evolved, it is best to maintain a healthy paranoia
      concerning the newer drugs--there are very few totally safe agents.

PMID- 8280817
TI  - Review article: the management of constipation in adults.
AB  - The successful management of constipation depends on defining the patient's
      symptoms, excluding secondary causes, and characterizing the abnormality of
      defecation. Constipation without gut dilatation is found commonly in pregnancy,
      the elderly, and those with the irritable bowel syndrome. In addition, there is a
      group of patients that has intractable, severe idiopathic constipation. Some have
      'slow transit' and open their bowels every 1-4 weeks. Others have a defecatory
      disorder with normal colonic transit. Constipation with gut dilatation is seen in
      Hirschsprung's disease, idiopathic megarectum and megacolon, chronic intestinal
      pseudo-obstruction and Chagas' disease. Constipation can also result from
      disturbance to the autonomic outflow of the gastrointestinal tract, and colonic
      function may be also affected by psychological factors. This review article
      discusses the presentation, investigation and management of patients with
      constipation.

PMID- 8280818
TI  - Does 40 mg omeprazole daily offer additional benefit over 20 mg daily in patients
      requiring more than 4 weeks of treatment for symptomatic reflux oesophagitis?
AB  - This study was designed to establish whether 40 mg omeprazole once daily exhibits
      sufficient additional efficacy over that of 20 mg omeprazole once daily in
      patients with symptomatic reflux oesophagitis requiring more than an initial 4
      week course of 20 mg omeprazole once daily (o.m.) to warrant routine use of the
      higher dose. Three hundred and thirteen patients were randomized to receive
      either 20 mg omeprazole (4 weeks) then 20 mg (second 4 weeks if not both healed
      and symptom-free after 4 weeks), or 20 mg omeprazole (4 weeks) then 40 mg
      omeprazole o.m. (second 4 weeks). One hundred and twenty-seven patients were
      healed and symptom-free after 4 weeks and left the study at that point. Taking
      the second treatment period in isolation, the healing rate (64% vs. 45%, P <
      0.02) and relief of heartburn (72% vs. 60%, P < 0.002) were greater among
      patients receiving 40 mg omeprazole o.m., demonstrating the existence of a dose
      response relationship for omeprazole. However, on completion, there were no
      significant differences between the patients randomized to the 20/20 mg (healed
      65%, asymptomatic 69%) or the 20/40 mg (healed 74%, asymptomatic 74%: both not
      significant differences compared with 20/20 mg) regimens. The magnitude of the
      difference in efficacy between 20 and 40 mg omeprazole in symptomatic reflux
      oesophagitis is insufficient to warrant the routine use of 40 mg in patients
      requiring more than 4 weeks' treatment with 20 mg omeprazole o.m.; continued
      treatment with 20 mg omeprazole for 4-8 weeks is the preferred option.

PMID- 8280819
TI  - The extent and pattern of gastro-oesophageal reflux in patients with scleroderma
      oesophagus: the effect of low-dose omeprazole.
AB  - Ambulatory 24-hour oesophageal pH studies were obtained from 11 patients with
      scleroderma who expressed either dysphagia (n = 6) or heartburn (n = 5) as their
      predominant oesophageal symptom. No significant differences were found in the
      extent of pattern of reflux between these two groups. The pH data of both
      scleroderma groups were combined and compared to an age- and sex-matched group of
      control subjects (n = 11). The reflux demonstrated by scleroderma patients was
      significantly greater than the control group in every category (P < 0.01). The
      percentage of time the pH was < 4.0 was not significantly different (P > 0.05)
      upright (29.9 +/- 19.8%) vs. supine (44.2 +/- 28.5%) in patients with
      scleroderma. Eight scleroderma patients underwent repeat pH studies while taking
      low-dose omeprazole (20 mg daily) and reflux was reduced significantly (P < 0.01)
      in all patients. The authors believe that 24-hour ambulatory oesophageal pH
      monitoring should be routinely conducted in scleroderma patients to provide
      quantitative reflux data, even when heartburn is not expressed as a symptom.
      Omeprazole, 20 mg daily, provides adequate protection from the H+ component of
      the refluxate.

PMID- 8280820
TI  - A prospective randomized study with mineral oil and oral lavage solution for
      treatment of faecal impaction in children.
AB  - Faecal impaction with or without encopresis is a very common problem. We
      performed a randomized, open-label, prospective study to compare the efficacy and
      acceptability of the treatment of faecal impaction using either mineral oil or
      pineapple-flavoured isotonic intestinal lavage solution containing polyethylene
      glycol-3350 (Colyte). Thirty-six patients over 2 years of age were randomized to
      receive either mineral oil or flavoured lavage solution. The dose of mineral oil
      was 2 to 8 tablespoons twice a day for two days (17 patients--Group I) and of
      lavage solution was 20 ml/kg/h for 4 hours on two consecutive days (19 patients-
      Group II). The patients were assessed for the presence of abdominal faecal
      masses, presence and consistency of rectal mass, perineal soiling before and two
      days after either of the randomly assigned treatment. The patients and parents
      were asked regarding the compliance with treatment, side-effects, number of bowel
      movements after treatment and willingness to try similar treatment if faecal
      impaction recurred. Patients in the lavage group had more frequent bowel
      movements, and showed more effective clearance of abdominal and rectal lumps (P <
      0.01) at the time of repeat examination at two days. However, they had some
      vomiting and were less compliant (P < 0.01) when compared to mineral oil
      patients. We conclude that balanced lavage solution effectively relieves faecal
      impaction, however, compliance with its use is poorer than that with mineral oil.

PMID- 8280821
TI  - Gastric retention of sucralfate gel and suspension in upper gastrointestinal
      diseases.
AB  - This study was designed to compare by scintigraphy the gastric retention of a new
      dosage form of sucralfate as gel (Gastrogel) with that of sucralfate suspension
      in 25 patients with upper gastrointestinal symptoms referred for routine
      endoscopy. After endoscopy 4 subgroups were defined: macroscopically normal
      mucosa (n = 7), antral gastritis and/or erosions (n = 6), gastric ulcer (n = 6)
      and duodenal ulcer (n = 6). Each patient received either sucralfate gel or
      sucralfate suspension in equivalent doses (5 ml containing 1 g sucralfate). Both
      formulations were labelled with 111 MBq 99mTc-DTPA before administration. The
      mean value of t1/2 in the total group was significantly longer when patients were
      taking sucralfate gel (61.6 min) compared to sucralfate suspension (33.8 min) (P
      < 0.001). The mean values of t1/2 were significantly longer for sucralfate gel
      compared to sucralfate suspension also among the subgroups (macroscopically
      normal P < 0.02, antral gastritis P < 0.05, gastric ulcer P < 0.02 and duodenal
      ulcer P < 0.05). After 2 and 3 hours, the percentage residual activity in the
      gastric area was significantly higher following administration of sucralfate gel
      compared to sucralfate suspension. This study has shown that, compared to
      sucralfate suspension, sucralfate gel persists longer in the stomach of patients
      with gastritis and peptic ulcer.

PMID- 8280822
TI  - Gastric acid suppression is greater during intravenous ranitidine infusion versus
      bolus injections of famotidine.
AB  - It has been proposed that famotidine may be effective in maintaining intragastric
      pH > or = 4 for up to 12 h with a single i.v. 20 mg bolus injection and thereby
      prevent acute stress-related mucosal haemorrhage. The present study was designed
      to compare a ranitidine continuous i.v. infusion (6.25 mg/h) vs. famotidine bolus
      injection (20 mg every 12 h) on 24-h intragastric pH and gastric acid secretion.
      Twenty-eight healthy volunteers (15 males, 13 females; 20-56 years) participated
      in two 24-h treatment periods; each test was in random order separated by 7-10
      days. After an overnight fast, subjects were intubated and gastric pH and acid
      secretion measured hourly. Whereas ranitidine maintained gastric pH above 4 for
      the entire 24-h period, mean pH steadily decreased to a nadir of 2.9 and 3.7,
      respectively, 12 h after each famotidine injection (P < 0.01 vs. ranitidine).
      Furthermore, gastric acid secretion increased to 4.4 +/- 1.2 mmol/h 12 h after
      famotidine injection compared to 1.1 +/- 0.3 mmol/h with ranitidine (P < 0.01).
      We conclude that ranitidine delivered as a continuous i.v. infusion (6.25 mg/h)
      is superior to bolus famotidine injections (20 mg) at 12-h intervals in
      suppressing gastric acid secretion and maintaining an intragastric pH > or = 4.
      More frequent famotidine dosing, or delivery by continuous i.v. infusion, may be
      required to provide prolonged acid suppression.

PMID- 8280823
TI  - Effect of a 5HT3-antagonist (ondansetron) on rectal sensitivity and compliance in
      health and the irritable bowel syndrome.
AB  - In some patients with the irritable bowel syndrome, rectal urgency and discomfort
      are major clinical problems and, under experimental conditions, these symptoms
      are perceived at lesser volumes of rectal distension than they are in
      asymptomatic controls. Further, a 5-hydroxytryptamine type-3 receptor antagonist
      increased the threshold for rectal discomfort in irritable bowel syndrome. Our
      aims were, (a) to measure rectal sensation during isobaric distensions of the
      rectum, and (b) to test the effect of another selective 5HT3-antagonist,
      ondansetron 0.15 mg/kg, on rectal sensitivity, colonic tone, rectal tone and
      manometric responses. Ten healthy volunteers and five patients with diarrhoea
      predominant irritable bowel syndrome were studied. A multilumen barostat
      manometric assembly was placed in the descending colon, and a second barostat
      balloon was positioned in the rectum. Tone in the wall of the colon and rectum
      was measured by the barostat balloon volume during a constant pressure clamp,
      while intraluminal pressures were recorded by manometry; perceived sensations
      were also recorded before and after the intravenous administration of ondansetron
      or placebo in blinded fashion. Rectal resistance to stretch was greater and
      rectal urgency was induced by lower distending pressures in irritable bowel
      syndrome, however, basal tone in the rectum was similar in health and irritable
      bowel syndrome. Ondansetron did not change rectal sensitivity (first sensation or
      urgency) or tone. Rectal distension did not alter tone in the descending colon or
      colonic manometry; ondansetron did not influence any index of colonic
      function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280824
TI  - An investigation into the effect of cimetidine pre-treatment on raft formation of
      an anti-reflux agent.
AB  - It is now becoming common practice to co-administer H2-receptor antagonists and
      anti-reflux agents in the treatment of reflux oesophagitis. The mechanism by
      which anti-reflux agents achieve flotation requires a small amount of gastric
      acid to be present in the stomach. This study investigated whether an anti-reflux
      agent would remain effective after the decrease in acid secretion produced by a
      typical clinical dosage regimen of cimetidine (400 mg q.d.s., 7 days). Gastric
      distribution and residence of a meal and an anti-reflux agent were assessed in 12
      normal subjects using gamma scintigraphy. The area under the gastric and fundal
      emptying curves demonstrated that Liquid Gaviscon (sodium alginate compound) had
      a significantly greater gastric residence than the meal, both during the control
      period and after cimetidine pretreatment, and that the majority of the Gaviscon
      was located in the fundus. The distribution of Gaviscon into the fundus was not
      affected by cimetidine pretreatment. Cimetidine pre-treatment slightly, but not
      significantly, increased the time for half the meal and the Gaviscon to empty
      from the stomach. The results suggest that the mechanism of action of Liquid
      Gaviscon is not compromised by concurrent H2-antagonist therapy.

PMID- 8280825
TI  - Treatment of active distal ulcerative colitis with immunoglobulin G enemas.
AB  - Seven patients with active distal ulcerative colitis were treated with IgG enemas
      given as a daily bedtime retention enema for two weeks. Evaluation of effect was
      assessed by means of sigmoidoscopy with biopsy, measuring acute phase reactants
      in peripheral blood, and measuring the faecal protein loss. Clinical signs of
      active disease were registered by the patients on a diary chart. Five patients
      completed the treatment period, two patients were withdrawn after 7 and 10 days
      due to deterioration of disease. Four patients did not register any effect,
      whereas one patient improved clinically. In conclusion, rectally administered IgG
      did not exert any effect on rectal ulcerative colitis in our study.

PMID- 8280826
TI  - Effect of steroids in an IBD model.

PMID- 8280828
TI  - Case-control study of risk factors for cervical squamous-cell neoplasia in
      Denmark. III. Role of oral contraceptive use.
AB  - The role of oral contraceptive (OC) use in relation to the risk of cervical
      neoplasia (squamous cell) was investigated in a population-based case-control
      study in Denmark of 586 women with histologically verified cervical carcinoma in
      situ (CIS), 59 women with invasive cervical cancer from Copenhagen, and 614
      controls drawn at random from the female population in the study area. Ever use
      of OCs was associated with an increased crude risk for carcinoma in situ
      (relative risk [RR] = 1.8, 95 percent confidence interval [CI] = 1.3-2.5). The
      crude risk in relation to invasive carcinoma was 1.6 (CI = 0.7-3.5). After
      adjustment for potential confounders (excluding human papillomavirus), the risks
      were marginally increased, but not statistically significant (CIS: RR = 1.4, CI =
      0.9-21: invasive: RR = 1.3, CI = 0.5-3.3). The risk increased with duration of
      use; compared with never users, the adjusted RR for carcinoma in situ was 1.9 (CI
      = 1.1-3.1) for women who had used OCs for six to nine years, and 1.7 (CI = 1.0
      2.7) for women who used OCs for 10 years or more. This was independent of years
      since last use since both recent and non-recent long-term users were at an
      increased risk. This trend in risk with duration did not apply to the same extent
      to invasive lesions. The observation that the risks related to OC use were found
      both in women who had ever had a Pap smear and in women who had never been
      screened previously may speak against detection bias as an important factor.

PMID- 8280827
TI  - Reproductive factors and risk of brain, colon, and other malignancies in Iowa
      (United States).
AB  - The influence of parity on the risk of cancers of the female breast and
      reproductive organs is well established. However, non-reproductive sites have
      received less attention. Mail questionnaire data gathered from incident female
      cases (169 brain; 332 colon; 260 rectal; 145 kidney; and 169 pancreas cancers),
      and 821 population-based controls in Iowa (United States) were used to measure
      the effect of parity and age at first birth on risk of these malignancies.
      Relative to nulliparous women, ever-parous women were at significantly decreased
      risk of brain cancer (odds ratio [OR] = 0.44, 95 percent confidence interval [CI]
      = 0.3-0.7) and of colon cancer (OR = 0.67, CI = 0.5-0.97), after adjustment for
      age and other risk factors. The OR for the other sites did not differ
      significantly from 1.0. The lower risk of brain cancer among parous women was
      similar in younger and older age groups, in patients diagnosed with glioblastoma
      and astrocytoma, and among ever- and never-smokers. The findings for colon cancer
      are consistent with observations from other studies. In the context of limited
      laboratory and clinical evidence implicating hormones in brain neoplasia, these
      findings may suggest a role for hormonal factors in brain cancer etiology.
      Hormonal factors deserve more detailed future consideration as risk factors in
      brain cancer.

PMID- 8280829
TI  - A study of diet and breast cancer prevention in Canada: why healthy women
      participate in controlled trials.
AB  - Little research has been undertaken to determine why healthy people agree to
      enroll in randomized controlled trials of cancer prevention. This study describes
      the beliefs of Canadian women participating in a trial designed to determine the
      effect of reducing dietary fat on the development of breast cancer. Healthier
      eating, nutritional counseling, contributing to science, and helping others were
      the most frequently cited advantages of participation. Weight control and general
      better health were specifically associated with the dietary regimens. Attending
      appointments and difficulties when eating out were the main disadvantages of
      participation. Suggestions that would promote adherence to the trial protocol
      also were elicited. Responses cited most often included opportunities to meet
      other participants, more nutritional counseling (particularly psychological
      tips), updates about the trial, and more recipes. Attention should be paid to
      these suggestions as they characterize some of the major determinants of
      adherence behavior.

PMID- 8280830
TI  - Descriptive epidemiology of primary cancer of the brain, cranial nerves, and
      cranial meninges in New Zealand, 1948-88.
AB  - We used New Zealand data on occurrence of different types of brain cancer to
      investigate: (i) a possible secular increase which has been seen worldwide and
      has generated considerable debate; (ii) possibly higher rates among Maori; and
      (iii) possibly higher risks related to social class and occupation. Data from the
      NZ Cancer Registry on the 5,684 brain cancers diagnosed among NZ residents from
      1948-88 were used to study the pattern of occurrence by gender, age, race,
      calendar year, social class, occupation, and histology. Age-standardized brain
      cancer incidence rates per 100,000 more than doubled over the 41-year period
      (from 2.9 to 6.9 in males and from 2.1 to 5.1 in females). A strong trend of
      increasing incidence with increasing social class is seen in males (Ptrend =
      0.01). Among Maori, the proportion of all brain cancer that is medulloblastoma is
      four times that among non-Maori, and the proportion of all brain cancers that
      lack histologic confirmation is about 40 percent higher. Elevated risks are seen
      among: dairy farmers (odds ratio [OR] = 3.4, 95 percent confidence interval [CI]
      = 1.9-6.0); sheep handlers (OR = 2.7, CI = 1.4-5.3); livestock workers (OR = 3.8,
      CI = 1.7-8.4); and farm managers (OR = 3.2, CI = 1.4-7.2); as well as among
      electrical engineers (OR = 8.2, CI = 20-34.7); electricians (OR = 4.6, CI = 1.7
      12.2); and other electrical workers. Brain cancer rates in NZ have increased
      steadily since 1948, but this increase has leveled off in the most recent five
      year period. Although brain cancer rates are likely to be underestimated among
      the Maori, an excess of medulloblastoma is evident in this group.

PMID- 8280831
TI  - Female mortality trends in Spain due to tumors associated with tobacco smoking.
AB  - Age- and period-specific mortality rates for esophageal, laryngeal, lung, and
      bladder cancers in Spanish women from 1952 to 1986 were analyzed using an age
      period-cohort model for each location. The four sites exhibit a similar pattern,
      characterized by a decline in mortality (cohort effect) in post-1900 generations.
      In the case of cancers of the esophagus and larynx, the model and curvature
      analysis show a slight rise in mortality in post-1932 generations. In cancers of
      the esophagus and lung, the period effect parallels the trend traced by the
      cohort effect. Prevalence estimates of smoking among women in Spain would seem to
      suggest that the degree of exposure in cohorts studied has been very low. The
      study indicates that smoking in Spanish women is relatively frequent only in
      recent generations and that this exposure has not produced, as yet, relevant
      variations in time trends. Special attention should be paid to the well known
      synergistic effect of smoking and alcohol consumption, which might already have
      determined changes in esophageal and laryngeal mortality.

PMID- 8280832
TI  - Cancer incidence and mortality in women occupationally exposed to chlorophenoxy
      herbicides, chlorophenols, and dioxins.
AB  - The association between exposure to chlorophenoxy herbicides contaminated with
      dioxins and occurrence of cancer has been studied mainly in male populations. In
      animal experiments, gender differences have been recorded in the cancer response
      to administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mortality and cancer
      incidence in an international cohort of 701 women from an International Register
      of Workers occupationally exposed to chlorophenoxy herbicides, chlorophenols, and
      dioxins is examined. Cause-specific, national death rates and cancer incidence
      rates were used as referents. Cancer risk was not increased overall, with a
      standardized incidence ratio (SIR) of 96 and 95 percent confidence interval (CI)
      of 64-137, based on 29 cases. Among workers exposed to those chlorophenoxy
      herbicides contaminated with TCDD, excess cancer incidence (for all sites) was
      observed (SIR = 222, CI = 102-422, 9 cases); this was highest in the first 10
      years after exposure. No excess was observed for breast cancer, the most common
      cancer in this cohort. Results on cancer mortality were consistent with those on
      incidence.

PMID- 8280833
TI  - Increased risk of renal cell cancer among women using diuretics in the United
      States.
AB  - Use of prescription diuretics and incidence of renal cell cancer have increased
      in the United States in the past 25 years. Recent interview-based epidemiologic
      studies have reported an association between diuretic use and renal cell cancer
      risk. Our study evaluated this hypothesis using, for the first time, medical
      records as the source of the information on prescription diuretic use. Using
      medical records of women from a prepaid health plan, we identified 191 cases and
      191 controls matched on age, membership duration, and membership at diagnosis.
      Diuretics use and history of potential confounding factors were ascertained by a
      standardized review of the medical records of each subject, without reference to
      case or control status. There was a strong and statistically significant
      association between renal cell cancer and prescription diuretics (odds ratio [OR]
      adjusted for hypertension, smoking, and obesity = 2.9, 95 percent confidence
      interval [CI] = 1.7-4.7). Risk tended to increase with dose, measured by number
      of prescriptions. Since renal cancer can induce hypertension, which is treated by
      diuretics, and thereby confound the association with diuretics, we examined
      diuretic use 10 or more years prior to diagnosis when secondary hypertension
      would be unlikely. The OR for prescriptions 10 or more years before diagnosis was
      3.5 (CI = 1.7-7.4). Our results support earlier reports of an excess risk of
      renal cell cancer among users of prescription diuretics and indicate need for
      further study to evaluate this relationship, especially due to the extensive use
      of diuretics and the increasing incidence of this cancer.

PMID- 8280834
TI  - Smoking, alcohol, coffee, tea, caffeine, and theobromine: risk of prostate cancer
      in Utah (United States).
AB  - Data from a population-based study of newly diagnosed cases of prostate cancer (n
      = 362) and age-matched controls (n = 685) conducted in Utah (United States)
      between 1983 and 1986 were used to determine if cigarette smoking, alcohol,
      coffee, tea, caffeine, and theobromine were associated with prostate cancer risk.
      These factors were examined since their use differs in the Utah population, which
      is comprised predominantly of members of the Church of Jesus Christ of Latter-day
      Saints (LDS or Mormon), from most other populations. Pack-years of cigarettes
      smoked, alcohol intake, and consumption of alcohol, coffee, tea, and caffeine
      were not associated with prostate cancer risk. Compared with men with very low
      levels of theobromine intake, older men consuming 11 to 20 and over 20 mg of
      theobromine per day were at increased risk of prostate cancer (odds ratio [OR]
      for all tumors = 2.06, 95 percent confidence interval [CI] = 1.33-3.20, and OR =
      1.47, CI = 0.99-2.19, respectively; OR for aggressive tumors = 1.90, CI = 0.90
      3.97, and OR = 1.74, CI = 0.91-3.32, respectively). We present biological
      mechanisms for a possible association between prostate cancer and theobromine.
      This finding needs further exploration in studies with a wider range of
      theobromine exposures and more men with aggressive tumors.

PMID- 8280835
TI  - Serum alpha 1-antitrypsin and duodenal ulcer.
AB  - Evaluation of serum alpha 1-antitrypsin levels in the South Asian population and
      its possible involvement in disease conditions such as duodenal ulcer has not
      been given due consideration. This is mainly because reports from European and
      North American countries indicate that the genetic deficiency of this protease
      inhibitor is rare among Asians of the subcontinent. Using isoelectric focusing
      (IEF) and radial immunodiffusion (RID) techniques, we analysed serum samples from
      100 normal, healthy adults and 50 patients with endoscopically proven duodenal
      ulcers to determine if there is a possible relationship between alpha 1
      antitrypsin phenotype and this disease. Five duodenal ulcer patients had low
      alpha 1-antitrypsin levels as well as SZ and S phenotype. None of the controls
      showed presence of S or SZ phenotypes. The normal or most common genetic form,
      MM, is the predominant phenotype in both controls and patients.

PMID- 8280836
TI  - Serum interleukin-8 in inflammatory bowel disease.
AB  - To investigate the relationship between serum concentrations of interleukin-8 (IL
      8) and disease activity in inflammatory bowel disease, serum IL-8 concentrations
      were measured by enzyme-linked immunosorbent assay (ELISA) in 93 patients.
      Interleukin-8 levels were compared with plasma interleukin-6 (IL-6) levels in 80
      of these patients. Interleukin-8 levels were also measured in ten patients with
      active Crohn's disease, before and after treatment with a defined formula
      polymeric diet. Of these patients, 70 out of 93 IL-8 concentrations were below
      the detection limit of the assay. Levels were higher in patients with active
      ulcerative colitis (median < 20 pg/mL, 75th centile value = 190) compared with
      inactive disease (median and 75th centile value < 20; P < 0.05). Interleukin-8
      concentrations correlated with a combined score for disease severity and extent
      (P = 0.01). Thirty-eight per cent (8/20) of patients with active Crohn's disease
      also had high levels of IL-8 but there was no significant difference between
      active and inactive disease. There was no correlation between serum IL-8 and
      plasma IL-6; on the contrary, very few patients had raised blood levels of both
      cytokines. In the diet treated group, serum IL-8 fell significantly after
      treatment (median = 37 pg/mL, range < 20-4615 before treatment, median < 20,
      range < 20-104 after treatment; P = 0.03). The results suggest that although IL-8
      may be involved in the inflammatory process in inflammatory bowel disease, it is
      a poor marker of disease activity.

PMID- 8280837
TI  - The effect of chilli and its pungent ingredient capsaicin on gastrointestinal
      transit in the rat.
AB  - The effect of chilli powder and its pungent ingredient capsaicin on
      gastrointestinal transit in the rat was studied. Fasted unanaesthetized male
      Sprague-Dawley rats (n = 144) received by gavage a test meal containing charcoal
      and cellulose in water or capsaicin solvent plus 51Cr as a radioactive marker.
      Either 100 or 200 mg of chilli powder (containing 0.13 and 0.26 mg of capsaicin,
      respectively) or 0.5 or 1 mg of capsaicin were added, the final volume of each
      meal being 1.5 mL. At 10 and 20 min, animals were killed and the amount of
      isotope that had left the stomach was measured, together with the distance the
      charcoal column had travelled along the small intestine. Compared to controls,
      animals given chilli powder emptied less of their gastric content at 10 and 20
      min, an effect partly reproduced by capsaicin. However overall gastric-small
      intestinal transit was unaffected by chilli powder or capsaicin. Another 12 male
      Sprague-Dawley rats received, under light ether anaesthesia, on six occasions at
      1-2 week intervals, the same six test meals as used in the previous experiment
      except that charcoal was not used. Total gut transit as measured by the amount of
      radioactive marker excreted in the stools at 18 and 24 h was unaffected by the
      use of chilli or capsaicin.

PMID- 8280838
TI  - Immunological responses against an autologous human hepatocellular carcinoma cell
      line.
AB  - We performed a detailed analysis of immune responses in a hepatocellular
      carcinoma (HCC) cell line and effector cells obtained from a patient with HCC. We
      examined the cytotoxic activity of natural killer (NK) cells, lymphokine
      activated killer (LAK) cells and cytotoxic T lymphocytes (CTL) against an
      autologous tumour cell line (SUHC-1) to investigate the immune mechanism of human
      lymphocytes against HCC cells. Cytotoxic T lymphocytes were induced by co
      culturing of peripheral blood lymphocytes (PBL) and SUHC-1 cells, mixed
      lymphocyte and tumour cell culture (MLTC). The susceptibility of SUHC-1 to NK and
      LAK cells was similar to that of other allogeneic cell lines, such as K562,
      PLC/PRF/5 and Mahlavu. Effector cells induced in the primary MLTC had high
      cytotoxic activity but were not specific for SUHC-1. Cytotoxic T lymphocytes with
      specific activity against SUHC-1 were induced after PBL were stimulated five
      times at 7-10 day intervals with SUHC-1 and low-dose recombinant interleukin-2
      (rIL-2), suggesting that as the culture progressed, broadly reactive effector
      cells disappeared and specific effector cells survived. The specific effector
      cells were identified as CD3+/CD4+ and CD3+/CD8+ T-lymphocyte subsets. The
      recognition mechanisms of CD3+/CD4+ CTL remain unresolved because the
      cytotoxicities were not inhibited by anti-CD4 and anti-major histocompatibility
      complex (MHC) class II monoclonal antibodies (MoAb). Treatment of cells with anti
      CD3, anti-CD8 and anti-MHC class I MoAb partially inhibited lysis. These results
      demonstrated that the T-cell receptor (TCR)/CD3 complex appeared to be involved
      in SUHC-1 specific antigen recognition and antigen recognition of CD3+/CD8+ CTL
      was MHC class I restricted.

PMID- 8280839
TI  - Role of the oestrogen receptor in liver regeneration in the male rat.
AB  - Partial hepatectomy in male rats results in raised serum oestrogen levels,
      nuclear binding of oestrogen receptor (ER) and feminization of certain aspects of
      hepatic metabolism. It has been proposed that these changes may have an important
      role in liver regeneration. The present study was performed to ascertain the
      effects of the oestrogen agonist diethylstilbestrol (DES), 2 mg/kg, and the
      oestrogen antagonist tamoxifen (TAM), 2 mg/kg, on liver regeneration induced by
      partial hepatectomy in the male rat. Regenerative activity was determined by
      incorporation of [3H]-thymidine into hepatic DNA as well as by measurement of
      liver remnant weight. Following partial hepatectomy, there was a trend towards an
      increase in liver remnant weight at 24 h in rats treated with DES (DES, 5.95 +/-
      1.52 g; vehicle, 4.87 +/- 0.66 g; P = 0.06) though by 48 h no effect was found.
      Tamoxifen treatment did not significantly affect liver weight at 24 h but by 48 h
      there was a highly significant reduction in liver remnant weight (TAM, 5.41 +/-
      0.85 g; vehicle, 7.31 +/- 1.43 g; P < 0.001). Neither DES nor TAM treatment
      influenced liver regeneration as determined by [3H]-thymidine incorporation into
      hepatic DNA. We conclude that pharmacologic manipulation of oestrogens does not
      influence the initiation of the regenerative process but that oestrogen may
      facilitate later phases of hepatic growth.

PMID- 8280840
TI  - Pathogenesis of centrilobular necrosis following congestion of the liver.
AB  - The exact pathogenesis of centrilobular necrosis following congestion of the
      liver is still unknown. We reviewed the clinical data related to systemic
      circulatory disturbance and histopathology of the liver and the gut in 320
      autopsy subjects. Congestion of the liver alone was associated only with atrophy
      and loss of hepatocytes in centrilobular areas, but not with hepatocellular
      coagulative necrosis. In many patients with coagulative necrosis of centrilobular
      hepatocytes and congestion of the liver, fibrin thrombi and neutrophil
      infiltration in the sinusoids, which are the characteristic histopathological
      features of the liver in endotoxaemia, were found in and around the necrotic
      area. Congestion, erosion or haemorrhage of the intestinal mucosa, which may
      allow entrance of endotoxin into the liver through the portal vein, was seen in
      such patients. Prolonged hypotension or shock, which may lead to portal
      endotoxaemia, was present in half the patients with centrilobular necrosis and
      congestion of the liver. These results suggest that not only congestion of the
      liver but also portal endotoxaemia may be involved in the pathogenesis of
      centrilobular necrosis in patients with congestion of the liver.

PMID- 8280841
TI  - Cytomegalovirus infection after liver transplantation in children.
AB  - Post-liver transplant cytomegalovirus (CMV) infection (seroconversion or virus
      isolation) and CMV disease (infection plus clinical signs and symptoms) were
      studied in relation to pretransplant recipient and donor serology, age,
      nutritional status and the effect of paediatric versus adult (reduced size)
      grafts. Of 70 children receiving 79 transplants, 26 (37%) had evidence of CMV
      infection, and eight (11.5%) had evidence of CMV disease, four of whom died. The
      primary infection rate (where the recipients were CMV negative) was 71% with
      mortality of 7% with most receiving a CMV-positive graft. The active secondary
      infection rate (reactivation or reinfection, where the recipients were CMV
      positive) was 60% with mortality of 12.5%. No significant differences in
      infection or disease rates were found comparing malnourished versus well
      nourished patients, or between those who received whole or reduced-size grafts.
      The high prevalence of CMV infections supports the view that clinical signs alone
      are inadequate to direct investigations for CMV. Both primary and active
      secondary CMV infection can result in serious morbidity and mortality in children
      receiving liver transplants. These data do not support the strategy of providing
      immunoprophylaxis to seronegative recipients only, at least in paediatric liver
      transplantation.

PMID- 8280842
TI  - Subcortical somatosensory evoked potentials in patients with hepatic
      encephalopathy caused by severe acute hepatitis.
AB  - We studied the median nerve stimulated somatosensory evoked potentials (SEP) of
      23 patients with hepatic encephalopathy (HE) resulting from severe acute
      hepatitis and 22 healthy volunteers. Ten patients who improved and survived more
      than 60 days were classified as Group 1 and the remaining 13 patients who died
      shortly after the SEP studies were classified as Group 2. The mean N9-N13
      interpeak latencies (IPL) were not different among control and two patient
      groups. The mean N13-N20 IPL of Group 2 was significantly prolonged when compared
      with normal controls (P < 0.001) and Group 1 (P < 0.001). Five of the six
      patients with abnormal N13-N20 IPL died of hepatic failure within 24 h after SEP
      testing. The occurrence of abnormal subcortical conduction together with cortical
      dysfunction suggested that brain damage in terminal hepatic encephalopathy was
      diffuse. The presentation of abnormal prolongation of N13-N20 IPL of SEP during
      the course of severe acute hepatitis indicated a poor prognosis. Peripheral
      somatosensory conduction is unaffected even in terminal HE.

PMID- 8280843
TI  - Model-derived assessment of urea appearance in response to alanine infusion: a
      quantitative measure of liver function in cirrhosis.
AB  - A three compartment mathematical model was used to analyse the urea response to
      an alanine infusion in six control subjects, and in 15 patients with liver
      cirrhosis and variable degree of hepatocellular failure. Model-derived
      coefficients were used to calculate two parameters (Ymax and Tmax), able to
      describe the theoretical response of the conversion of amino acid derived
      nitrogen into urea, in response to a unit impulse in alanine concentration. They
      correspond to the maximum rate of conversion of nitrogen from an intermediary
      pool into urea and to the time delay between the impulse and Ymax, respectively.
      In cirrhosis, the apparent volume of distribution of infused alanine was smaller
      than in controls, while the conversion of alanine nitrogen into an intermediary
      pool of nitrogen and finally into urea nitrogen were both reduced. Also Ymax was
      reduced by 50% in cirrhosis, whereas Tmax was increased by 50%, and both
      significantly correlated with galactose elimination capacity (GEC; R2 = 0.706 and
      R2 = 0.505, respectively) and with antipyrine clearance (Ap Cl; R2 = 0.823 and R2
      = 0.576, respectively). Model-derived assessment of urea appearance in response
      to alanine infusion is able to quantify the functional liver cell mass, and may
      prove useful for the study of nitrogen metabolism in cirrhosis, mainly in
      relation to encephalopathy.

PMID- 8280844
TI  - Evaluation of the maximal excretion rate of indocyanin green as a prognostic
      indicator in patients undergoing biliary decompression for obstructive jaundice.
AB  - To assess the postoperative outcome of jaundiced patients and to select the
      optimal timing for surgical intervention, indocyanin green (ICG) concentrations
      in the bile were measured after biliary decompression in patients with
      obstructive jaundice. The maximal excretion rate of ICG in the bile was
      calculated as a function of time (ICG Bmax). Among 59 patients with positive ICG
      Bmax values, morbidity was 15.2% and postoperative hospital mortality was 3.3%.
      However, the morbidity and mortality in nine patients with values between -0.5
      and 0 were 88.8 and 44.4%, respectively. The 13 patients with in ICG Bmax below 
      0.5 had a 76.9% morbidity and a 61.5% mortality. The patients with ICG Bmax
      values below 0 showed a significantly higher morbidity and mortality than
      positive ICG Bmax patients. In patients showing ICG Bmax values below -0.5,
      surgery is contraindicated despite intensive postoperative care. The ICG Bmax
      value improved according to the increasing effect of biliary decompression. The
      index is useful not only as a prognostic index in the early phase of biliary
      decompression but also as an index of bile secretory capacity at a given time. By
      means of time course measurement of this index, the suitable time for operation
      can be determined. The ICG Bmax is a useful and reliable indicator in the
      assessment of hepatobiliary functional reserve in jaundiced patients after
      biliary decompression and prior to further surgical intervention.

PMID- 8280845
TI  - Local spread of HDV infection transiently occurring in Japan.
AB  - Hepatitis B virus (HBV) carriers and patients with acute hepatitis B living in
      the Kamigoto islands, a part of Japan with a high incidence of HBV carriage, were
      retrospectively tested for serum anti-hepatitis D virus (anti-HDV) and they were
      compared with the inhabitants of Oita City (an area with an average HBV carriage
      rate). The prevalence of anti-HDV in HBV-infected individuals was 8.3% (42/507)
      in Kamigoto and 0% (0/101) in Oita City. With one exception, all of the positive
      serum samples in Kamigoto were collected before 1986, and the mean age of the
      positive individuals was significantly younger than that of the negative
      individuals (P < 0.005). Among the 42 anti-HDV-positive patients, nine (21%) had
      definite liver disease. The route of infection was uncertain in most cases (i.e.
      sporadic), but two pairs of mothers and children were detected. Although the
      prevalence of anti-HDV positivity in Japan has been reported to be very low
      (about 1% or less), the present investigation showed that the local spread of HDV
      infection in Kamigoto occurred on a minor scale up to 1986. The infections
      presumably resulted from the closed environment and the high incidence of HBV
      carriage in these islands. Accordingly, there could be a considerable risk of the
      outbreak of HDV infection in the future under similar conditions, even in
      countries where the disease has never been detected previously.

PMID- 8280846
TI  - A follow up of 53 adult patients alive beyond 2 years following liver
      transplantation.
AB  - Although hepatic transplantation is now a well-accepted treatment modality for
      end-stage liver diseases there are little detailed data on the clinical profile
      of patients who survive beyond 1 year following transplantation. The aim of this
      study was to develop a cross-sectional profile on 53 adults who have survived
      beyond 2 years following liver transplantation. These patients have been followed
      for a mean of 43.5 months (range 24-84) since the time of transplant. Nineteen
      patients had persisting liver enzyme abnormalities, 11 due to chronic viral
      hepatitis (seven hepatitis C virus, three hepatitis B virus), four due to biliary
      disease. Two had post severe rejection, one steatosis secondary to obesity while
      in one the aetiology was unclear. Nineteen (36%) of patients required anti
      hypertensive medications. The median doses of Prednisone, Cyclosporin and Imuran
      were 7.5, 300 and 50 mg daily, respectively. The mean serum creatinine was 117 +/
      27 mumol/L. However 22 (41%) had an elevated serum creatinine (> 120 mumol/L)
      but in only seven was the serum creatinine > 150 mumol/L. Fourteen (26%) of
      patients were obese (body mass index > 30) whilst 46% had a higher than
      recommended serum cholesterol (mean level 5.6 +/- 1.5 mumol/L). There has only
      been one case of internal malignancy (lymphoma) although 19 patients attend
      regular dermatological review for skin cancer surveillance. Forty-eight patients
      had a Karnofsky Score > 80. In conclusion, the vast majority of these patients
      have excellent clinical function but some caution is required with respect to
      renal function, hypertension, obesity and mild hypercholesterolaemia.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8280847
TI  - Endotoxaemia in patients with liver cirrhosis and upper gastrointestinal
      bleeding: detection by the chromogenic assay with plasma Tween 80 pretreatment.
AB  - A recently developed chromogenic endotoxin assay with plasma Tween 80
      pretreatment was compared with the conventional dilution and heating method.
      Plasma endotoxin was measured in patients with liver cirrhosis and upper
      gastrointestinal (GI) bleeding by these methods. Plasma endotoxin concentration
      was calculated from an individual internal standard curve by adding three
      different standard endotoxin solutions to each sample. By the conventional
      heating method, added standard endotoxin gave different OD values in each sample
      and the slope of the standard curve showed interindividual variations. When
      sample plasma from chronic alcoholics was pretreated with 1% Tween 80 and
      ultrasonification after heating, the slope of standard curves was somewhat
      increased and interindividual variation was minimized. Significantly higher
      plasma endotoxin levels in cirrhotics with upper GI bleeding compared with those
      without upper GI bleeding was detected by this Tween 80 method. There was a
      strongly positive correlation between the endotoxin levels determined by this
      method and those determined by the perchloric acid method and endotoxin-specific
      substrate in patients with upper GI bleeding. Endotoxin levels, which were
      elevated 1-2 days after the bleeding, tended to decrease as patients recovered.
      In summary, the recovery of endogenous and exogenous endotoxin from plasma sample
      was increased by adding Tween 80 before the chromogenic substrate assay.
      Transient elevation of plasma endotoxin was demonstrated by this Tween 80 method
      in patients with liver cirrhosis and upper GI bleeding.

PMID- 8280848
TI  - Intestinal pseudo-obstruction, type 1 anti-neuronal nuclear antibodies and small
      cell carcinoma of the lung.
AB  - Intestinal pseudo-obstruction is a rare paraneoplastic manifestation of small
      cell carcinoma of the lung. This report documents a further case associated with
      neuronal degeneration of enteric neural plexuses and a high serum titre of
      immunoglobulin G (IgG) type 1 anti-neuronal nuclear antibodies (ANNA-1).

PMID- 8280849
TI  - Concomitant adenosquamous carcinoma of the common bile duct and early
      adenocarcinoma of the gall-bladder.
AB  - We report a 59 year old male with obstructive jaundice and a clinical diagnosis
      of carcinoma of the midportion of the common bile duct. Examination of the
      surgical specimen revealed a small tumour in the neck of the gall-bladder.
      Histologic examination revealed the tumour in the common bile duct was an
      adenosquamous carcinoma whereas that in the gall-bladder was an early papillary
      adenocarcinoma. Thus, this is a rare case of the simultaneous development of
      adenosquamous carcinoma and early papillary adenocarcinoma in the biliary tree.

PMID- 8280850
TI  - A rupture of lung metastasis of hepatocellular carcinoma causing haemothorax.
AB  - A 67 year old male with non-resectable hepatocellular carcinoma (HCC) in both
      lobes and liver cirrhosis was treated with transcatheter arterial embolization
      and regional chemotherapy. He was doing well for 18 months. He was readmitted for
      fever, chest pain and multiple pulmonary metastases. During interleukin-2
      therapy, he suddenly developed dyspnoea and palpitation, and was in shock. Left
      sided haemothorax was confirmed by draining 3 L of fresh blood. In spite of
      intensive care, he died within 36 h. Autopsy showed that the haemothorax was
      caused by rupture of one of the metastases in the upper lobe of the left lung,
      and that the primary HCC was totally necrotic. Survey of the literature failed to
      find a report of fatal bleeding from a lung metastasis of HCC.

PMID- 8280851
TI  - Increased expression of heat-shock protein 27 kDa in Alzheimer disease: a
      preliminary study.
AB  - Stress-response (heat shock) proteins (hsps) are induced in living cells under
      pathological conditions, including diseases of the central nervous system.
      Increased synthesis of hsps is suggested to play a role in preventing neuronal
      injury in Alzheimer disease (AD). Using a highly specific antibody we have
      studied the expression of heat shock protein 27 kDa (hsp 27), in the brains of AD
      and non-demented, age-matched control patients. Immunoblotting and
      immunohistochemical methods were used. We report here that in the human brain in
      the normal condition the expression of hsp 27 is low and limited to the vessels,
      subpial astrocytes and single astrocytes of the white matter. There is a
      significant increase in the expression of hsp 27 in the cortex of AD. In AD, the
      immunoreaction is mainly localized in proliferating astrocytes establishing a
      pattern of astrocytic gliosis. These findings are the first to show the presence
      of hsp 27 in human cerebral tissue in normal conditions and its induction in AD.

PMID- 8280852
TI  - Dissimilar patterns of degeneration in brain following four different addictive
      stimulants.
AB  - Patterns of neural degeneration were compared following continuous administration
      of four drugs of addiction, each of which induces model psychoses in chronic
      addicts. D-amphetamine (D-Amph), cocaine (Coc), or phencyclidine (PCP) were
      administered continuously over a 5-day period. Both D-Amph and Coc induced
      pronounced degeneration in fasciculus retroflexus, but only D-Amph further
      induced substantial degeneration in striatum. Continuous PCP produced entirely
      different degeneration largely confined to the posterior entorhinal cortex,
      ventral dentate gyrus, and cingulate cortex. Methamphetamine (Meth) administered
      in the very high dose but less prolonged drug regimen often employed in studies
      of dopamine toxicity induced pronounced degeneration in striatum, but widespread
      degeneration in many other regions as well. These results indicate that drugs of
      abuse with psychotomimetic properties induce distinctively different patterns of
      neural degeneration, a finding with implications for theories of addiction and
      psychosis. They predict two different anatomical loci for alterations in
      psychosis: fasciculus retroflexus and ventral parahippocampus and hippocampus.

PMID- 8280853
TI  - Reduced transferrin binding in Down syndrome: a route to senile plaque formation
      and dementia.
AB  - Plasma transferrin binding in Down syndrome and Alzheimer's disease is
      significantly reduced compared with age matched controls and it was thought this
      may help elucidate a pathological time sequence for the onset of dementia in Down
      syndrome. In Down syndrome, there was a reduction in gallium and aluminium
      transferrin binding both with age and the onset of dementia. Non-transferrin
      bound gallium species were identified as non-transportable phosphate or silicate.
      Thus, the route of entry of metals into the brain must be via a transferrin
      mediated complex only. A clear sequence of pathological events has been
      demonstrated in Down syndrome which shows the pathway to development of plaques
      and dementia and this is believed to have an immunological origin.

PMID- 8280854
TI  - Prion protein is abnormally accumulated in inclusion-body myositis.
AB  - In muscle biopsies of 8 sporadic inclusion-body myositis (S-IBM) and 4 hereditary
      inclusion-body myopathy (H-IBM) patients, vacuolated muscle fibers contained
      within their vacuoles strongly immunoreactive inclusions with 2 polyclonal and 1
      monoclonal antibodies against prion protein (PrP). By light-microscopy, PrP
      deposits co-localized with beta-amyloid protein (A beta) and ubiquitin (Ub). By
      immuno-electronmicroscopy, both PrP and A beta were present on amorphous material
      and on 6-10 nm amyloid-like fibrils; and PrP and Ub co-localized on cytoplasmic
      twisted tubulofilaments (TTFs) and on amorphous material. Our study provides the
      first demonstration of abnormally accumulated PrP in pathological tissue other
      than brain, and it suggests that PrP may play a role in the pathogenesis of IBM.

PMID- 8280855
TI  - Lateral gap junction connections between retinal amacrine cells summating
      sustained responses.
AB  - Vertebrate retinal amacrine cells produce transient or sustained responses.
      Sustained depolarizing amacrine cells in the dace retina were identified by their
      intracellularly recorded responses to light flashes. The response amplitude
      produced a notable spatial summation which exceeded that of individual dendritic
      arbors. When sustained type amacrine cells were intracellularly injected with
      Lucifer Yellow and biocytin, there was extensive transfer of biocytin, but not
      Lucifer Yellow, to surrounding cells with similar cellular morphology.
      Ultrastructural analysis of the interconnections by electron microscopy revealed
      the presence of gap junctions at the contact area, which did not include
      conventional synapses. Present results demonstrate that sustained response
      amacrine cells make direct electrical connections between the cells of the same
      type and electrical coupling may contribute to extension of their receptive
      fields.

PMID- 8280856
TI  - Hair cell overproduction in the developing mammalian cochlea in culture.
AB  - Hair cells transduce acoustics into electrical signals that are conveyed to the
      brain by auditory nerve fibres. Hair cells loss in mammals due to ageing,
      ototoxic drugs or noise, leads to irreversible hearing impairment. One objective
      would be to replace lost cells by regeneration or production of new hair cells.
      We report an overproduction of hair cells in the developing cochlea of the rat in
      culture without adding drugs, without previous injury or special manipulations of
      the explants. The overproduction of hair cells does not depend on the culture
      medium or on the innervation of the organ of Corti. Younger foetal explants show
      higher potency for the production of supplementary hair cells than older ones.
      This is the first report of the generation of extra hair cells in mammals without
      previous hair cell loss or treatment with drugs.

PMID- 8280857
TI  - Changes of spirodecanone binding in the gerbil hippocampus after cerebral
      ischaemia.
AB  - Using quantitative receptor autoradiography, spirodecanone binding was evaluated
      in the gerbil hippocampus 1 h-1 month after cerebral ischaemia of 10 min. The
      spirodecanone binding was unaffected in the hippocampus up to 48 h after
      ischaemia. Thereafter, increased binding was found in the stratum radiatum of
      hippocampal CA1 sector 7 days and 1 month after ischaemia. Other hippocampal
      regions showed no significant alterations in the spirodecanone binding. A
      histological study revealed that the hippocampal CA1 sector was severely damaged
      7 days and 1 months after ischaemia. These results demonstrate that spirodecanone
      binding sites are located on interneurones or glial cells in the hippocampal CA1
      sector.

PMID- 8280858
TI  - Macrophage-enhanced neurite regeneration of adult dorsal root ganglia neurones in
      culture.
AB  - To study the effects of macrophages on nerve regeneration, purified low
      population dorsal root ganglia (DRG) neurones from adult mice were cultured in
      protein-free medium (PFM) or in conditioned media (CM) from peritoneal
      macrophages cultured in PFM. In PFM, only 20% of the neurones survived at 5 days
      in culture, but the macrophage CM more than doubled the proportion of neurone
      survival and neurite extension of controls. These factors did not act on superior
      cervical ganglia (SCG) neurones, and were considered as being proteins because of
      their trypsin-sensitive property. Additionally, they may be different from the
      previously known neurotrophic factors derived from macrophages, because the
      target cells and effective concentration of these factors were different from
      those of known ones. The factors investigated in this study may play an important
      role in nerve regeneration.

PMID- 8280859
TI  - Parietal epileptic mirror focus detected with a whole-head neuromagnetometer.
AB  - Whole-head magnetoencephalographic recordings revealed two parietal epileptic
      foci in homotopic areas of the hemispheres. The discharges occurred 17-20 ms
      later on the left than on the right hemisphere, implying the existence of a left
      sided mirror focus. The foci were about 1 cm posterior to the hand primary
      somatosensory area, identified by evoked response measurements, and thus
      suggested epileptic activity at the parietal association cortex, in agreement
      with the observed callosal conduction time.

PMID- 8280860
TI  - Serotonin in the raphe nuclei: regulation by light and an endogenous pacemaker.
AB  - Temporal changes of serotonin (5-HT) content in the median (MRN) and dorsal (DRN)
      raphe nuclei were measured in rats kept under various lighting conditions.
      Serotonin content in the MRN and DRN under light-dark (LD) condition showed
      diurnal rhythmicity, with a peak during early light phase and a trough during the
      dark phase. In constant dark (DD) condition, a single peak was observed and was
      out of phase to the 5-HT peak found under LD condition. Animals exposed to
      constant light (LL) after 2 days in DD showed marked increase in 5-HT after
      lights on. These results suggest that changes in 5-HT in the MRN and DRN are
      regulated by an endogenous pacemaker and by light.

PMID- 8280861
TI  - In vivo EEDQ dose-dependently inactivates rat brain 5-HT receptors but not 5-HT
      uptake sites.
AB  - The present study investigates the inactivation and recovery of brain serotonin
      (5-HT) recognition sites by EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2,
      dihydroquinoline). Adult male Sprague-Dawley rats were given a single s.c.
      injection of vehicle (1:1 EtOH/H2O) or EEDQ (1-20 mg kg-1) and sacrificed at 4 h
      and 7 days (10 mg kg-1 dose) post-injection. EEDQ dose-dependently reduced the
      Bmax of 5-HT1A(3H-DPAT),5-HT1B(125I-CYP),5-HT2(3H-ketanserin) and 5-HT2/1C(125I
      DOI) receptors in cortical homogenates. In contrast, EEDQ was without effect on
      the 5-HT transporter recognition site (3H-paroxetine). No significant changes in
      affinity were observed for 5-HT1B, 5-HT2 or 5-HT2/1C receptors. The rank order of
      sensitivity to EEDQ inactivation was: 5-HT1A > 5-HT1B > 5-HT2 approximately 5
      HT2/1C >>> 5-HT uptake sites. This study demonstrates: (1) differential EEDQ
      inactivation and recovery of 5-HT receptors and (2) lack of EEDQ inactivation of
      the 5-HT transporter.

PMID- 8280862
TI  - Chronic morphine increases calbindin D28k in rat striatum: possible NMDA receptor
      involvement.
AB  - The neuronal intracellular calcium-binding protein calbindin D28k is a
      neurochemical marker in the striatum, normally expressed in the matrix
      compartment and absent from the mu-opiate receptor-enriched striosomal (patch)
      compartment. Because chronic treatment with morphine has been reported to
      increase calcium levels in synaptosomes of rat striatum, we studied effects of
      morphine on calbindin immunoreactivity (ir) in rat brain, using
      immunocytochemistry. Treatment with morphine for 5 days increased calbindin-ir in
      the striatal matrix, and induced intense calbindin-ir in the patch compartment.
      Increased calbindin-ir in patches persisted through day 14 post-morphine. Co
      administration of the NMDA receptor antagonist MK-801 blocked the morphine
      induced increase in calbindin-ir in patches. We suggest that chronic morphine
      treatment may increase calcium and calbindin levels via increased glutamatergic
      transmission in striatum. These findings are consistent with reports that MK-801
      inhibits tolerance to morphine, and provide a possible mechanism and anatomical
      substrate for this inhibition.

PMID- 8280863
TI  - Direct action of metyrapone on brain: implication in feeding.
AB  - While the inhibitory effect of metyrapone on the biosynthesis of adrenal
      corticosteroid hormones is well known, the drug has not been tested for central
      actions. The present study is aimed at finding out the direct central action of
      metyrapone, if any, employing feeding behaviour as a test parameter. Low doses of
      metyrapone (10-1000 ng) administered via an i.c.v. route reduced the food intake
      in a dose dependent manner; the effect was functionally antagonized by
      concomitant administration of anti-CRF antisera. The results reveal for the first
      time, that metyrapone might be capable of exerting a direct action on the adrenal
      cortex.

PMID- 8280864
TI  - Concomitant administration of MK-801 and desipramine enhances extracellular
      concentration of dopamine in the rat prefrontal cortex.
AB  - The interaction between the antidepressant drug desipramine and the non
      competitive NMDA receptor antagonist MK-801 was investigated at the level of
      dopamine release in the rat prefrontal cortex. Peripheral administration of MK
      801 (0.2 mg kg-1) or desipramine (10 mg kg-1) evoked weak enhancement of the
      extracellular dopamine concentration in the rat PFC. Desipramine and MK-801 given
      jointly in doses which by themselves evoked a mild alteration of dopamine outflow
      (10 mg and 0.2 mg kg-1 respectively) produced pronounced enhancement of the
      extracellular concentration of dopamine in the rat prefrontal cortex. It is
      suggested that the non-competitive NMDA receptor antagonist may enhance the
      efficacy of classical antidepressant drugs.

PMID- 8280865
TI  - Non-NMDA glutamate receptors are involved in the maintenance of status
      epilepticus.
AB  - The role of N-methyl-D-aspartate (NMDA), non-NMDA glutamate, metabotropic and
      muscarinic receptors in the maintenance of status epilepticus (SE) was
      investigated. SE induced in rat brain by continuous electrical stimulation to the
      hippocampus was terminated by intracerebroventricular (i.c.v.) injection of the
      non-NMDA antagonists DNQX and NBQX, but not by the muscarinic antagonists
      scopolamine or atropine, or the metabotropic antagonist AP3. The NMDA antagonist,
      MK-801 suppressed motor seizure activity but did not terminate electrographic
      seizures when generalized SE was induced, suggesting that both non-NMDA and NMDA
      receptors maintain generalized convulsive SE. However, when limbic SE was
      induced, MK-801 also had an anticonvulsant effect suggesting differences in the
      mechanisms maintaining limbic SE and generalized SE.

PMID- 8280867
TI  - Blastogenesis. Normal and abnormal. Proceedings of the 2nd international workshop
      on fetal genetic pathology. Big Sky, Montana, October 12-16, 1991.

PMID- 8280866
TI  - Nitric oxide increases dopamine and serotonin release in the medial preoptic
      area.
AB  - Nitric oxide (NO) is becoming recognized as an important intercellular messenger
      in the brain. The present experiment used microdialysis to examine the potential
      role of NO in the regulation of dopamine (DA) and serotonin (5-HT) release in the
      medial preoptic area (MPOA) of freely moving male rats. The NO precursor L
      arginine (L-Arg, 100 microM), administered into the MPOA via the dialysis probe,
      increased extracellular levels of DA, 5-HT, and the major metabolites of DA.
      These increases were blocked by the coadministration of the NO synthase inhibitor
      N-monomethyl L-arginine (NMMA, 400 microM). The inactive isomer D-arginine (100
      microM) was ineffective, and NMMA by itself decreased DA below baseline levels.
      Thus, NO may modulate the release of DA and 5-HT in the MPOA.

PMID- 8280868
TI  - The role of segmentation in the development of the branchial region of higher
      vertebrate embryos.

PMID- 8280869
TI  - Developmental abnormalities resulting in short umbilical cord.

PMID- 8280870
TI  - Conjoined twins: implications for blastogenesis.
AB  - It is difficult to draw sweeping general conclusions about the blastogenesis of
      CT, principally because so few thoroughly studied cases are reported. It is to be
      hoped that methods such as painstaking gross or electronic dissection will
      increase the number of well-documented cases. Nevertheless, the following
      conclusions can be proposed: 1. Most CT can be classified into a few main
      anatomic types (or paradigms), and there are also rare transitional types that
      show gradation between the main types. 2. Most CT have two full notochordal axes
      (Fig. 5); the ventral organs induced along these axes may be severely
      disorientated, malformed, or aplastic in the process of being arranged within one
      body. Reported anatomic types of CT represent those notochordal arrangements that
      are compatible with reasonably complete embryogenesis. New ventro-lateral axes
      are formed in many types of CT because of space constriction in the ventral
      zones. The new structures represent areas of "mutual recognition and
      organization" rather than "fusion" (Fig. 17). 3. Orientations of the pairs of
      axes in the embryonic disc can be deduced from the resulting anatomy. Except for
      dicephalus, the axes are not side by side. Notochords are usually "end-on" or
      ventro-ventral in orientation (Fig. 5). 4. A single gastrulation event or only
      partial duplicated gastrulation event seems to occur in dicephalics, despite a
      full double notochord. 5. The anatomy of diprosopus requires further
      clarification, particularly in cases with complete crania rather than anencephaly
      equivalent. Diprosopus CT offer the best opportunity to study the effects of true
      forking of the notochord, if this actually occurs. 6. In cephalothoracopagus,
      thoracopagus, and ischiopagus, remarkably complete new body forms are constructed
      at right angles to the notochordal axes. The extent of expression of viscera in
      these types depends on the degree of noncongruity of their ventro-ventral axes
      (Figs. 4, 11, 15b). 7. Some organs and tissues fail to develop (interaction
      aplasia) because of conflicting migrational pathways or abnormal concentrations
      of morphogens in and around the neoaxes. 8. Where the cardiovascular system is
      discordantly expressed in dicephalus and thoracopagus twins, the right heart is
      more severely malformed, depending on the degree of interaction of the two
      embryonic septa transversa. 9. The septum transversum provides mesenchymal
      components to the heawrt and liver; the epithelial components (derived fro the
      foregut[s]) may vary in number from the number of mesenchymal septa transversa
      contributing to the liver of the CT embryo.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8280871
TI  - Triploidy with complementary recombinant 7s from a paternal inversion 7.

PMID- 8280872
TI  - Teratothanasia: prenatal loss of abnormal conceptuses and the prevalence of
      various malformations during human gestation.

PMID- 8280873
TI  - Diprosopus: a pregastrulation defect involving the head, neural tube, heart, and
      diaphragm.

PMID- 8280874
TI  - Bladder exstrophy and exomphalos in successive pregnancies.

PMID- 8280875
TI  - Experience with a fetal dysmorphology/pathology service in an academic medical
      center.

PMID- 8280876
TI  - X-linked VACTERL with hydrocephalus: the VACTERL-H syndrome.

PMID- 8280877
TI  - Cephalothoracopagus (janiceps) conjoined twins: computerized three-dimensional
      reconstruction.

PMID- 8280878
TI  - Computerized three-dimensional reconstruction of the brain of normal and
      holoprosencephalic human embryos.

PMID- 8280879
TI  - Conjoined twins: report of a Brazilian twin belonging to the category duplicatas
      incompleta, an atypical parasite twinning type.

PMID- 8280880
TI  - Amniotic band sequence: Streeter hypothesis revisited.

PMID- 8280881
TI  - Computerized three-dimensional reconstruction of two human symmelic fetuses.

PMID- 8280882
TI  - Blastogenesis and the "primary field" in human development.

PMID- 8280884
TI  - Torque deformation sequence associated with short umbilical cord and abdominal
      wall defect.

PMID- 8280883
TI  - Fetal cystic hygroma in sibs: developmental analysis of coexistent cardiovascular
      malformations relevant to pathogenesis.

PMID- 8280885
TI  - Cyclotocephaly: severe form of midline malformation association.

PMID- 8280886
TI  - Abnormal spleen lobulation and short pancreas.

PMID- 8280887
TI  - Hemodynamic mechanisms in cardiac malformations.

PMID- 8280888
TI  - Adrenal hyperplastic nodules in Wiedemann-Beckwith syndrome.

PMID- 8280889
TI  - Glutaric aciduria type II, an unusual cause of prenatal polycystic kidneys:
      report of prenatal diagnosis and confirmation of autosomal recessive inheritance.

PMID- 8280890
TI  - Heteropagus epignathus: report on a Brazilian twin.

PMID- 8280891
TI  - Holoprosencephaly, hamartomatous growth of the cerebrum, dysplastic gangliocytoma
      of the cerebellum, unique brain anomalies, and renal agenesis in a Brazilian
      infant born to a diabetic mother: a clinical and pathologic study.

PMID- 8280892
TI  - The effect of confined placental mosaicism on development of the human aneuploid
      conceptus.
AB  - The rate of meiotic errors in gametogenesis is high, resulting in approximately
      30% of cleaving embryos with chromosomal defect. In addition, mitotic errors
      occur commonly in chromosomally normal and abnormal embryos. The most likely
      outcome of the mitotic error is CPM. Mitotic mutation in trisomic blastocysts may
      lead to diploid/trisomic trophoblast with intrauterine survival of the trisomic
      fetus or may result in a diploid fetus supported by a trisomic placenta. The
      outcome of pregnancies with a trisomic placenta and diploid fetus largely depends
      on the specific chromosome involved and on the presence or absence of uniparental
      disomy in the fetus.

PMID- 8280893
TI  - Early spontaneous abortion: morphologic and karyotypic findings in 3,912 cases.

PMID- 8280894
TI  - On the biologic nature of associations: evidence from a study of radial ray
      deficiencies and associated malformations.

PMID- 8280895
TI  - A review of caudal dysgenesis and its pathogenesis as illustrated in an animal
      model.

PMID- 8280896
TI  - Demonstration of low density lipoprotein receptor in human colonic carcinoma and
      surrounding mucosa by immunoenzymatic assay.
AB  - In order to verify the presence of Low Density Lipoprotein Receptor (LDLR) in
      cellular membranes isolated from human colonic tissue, samples from the
      neoplastic colorectum and the normal surrounding mucosa were studied by an enzyme
      linked-immunosorbent assay. A monoclonal antibody against the human LDLR was
      used. The LDLR content revealed a considerable inter-individual variation. In 36
      out of 53 cases (68%) there was no LDLR presence in either normal or neoplastic
      tissue samples. In 5 out of 53 cases (9.4%), LDLRs were detected in both types of
      tissue samples, in 9 cases out of 53 (17%) LDLRs were present in neoplastic
      tissue, while in 3 out of 53 cases (5.6%) only in normal mucosa. The anti-LDLR
      mono-clonal antibody (mAb) binding was significantly higher in neoplastic tissue
      samples than normal surrounding colonic mucosa ones. Sex, age, body mass index
      (BMI), serum cholesterol, tumour site, histologic grading and Dukes' stage did
      not seem to be associated with LDLR presence.

PMID- 8280897
TI  - Non-cardia gastric adenocarcinoma and Helicobacter pylori infection.
AB  - The seroprevalence of IgG antibodies to Helicobacter pylori (Hp-Ab) was studied
      in 47 patients (29M, 18F, mean age +/- SD: 62.44 +/- 12.63 years) with non-cardia
      gastric carcinoma using an enzyme-linked immunosorbent assay. Controls were: a)
      50 healthy people well-matched with the cancer patients; b) 50 patients with
      dyspepsia well matched with the cancer patients. Hp-Ab were detected in 72.3% of
      patients with gastric carcinoma, in 68% of healthy people and in 88% of
      dyspeptics. No significant associations were found between H. pylori infection
      and gastric cancer patients as a whole (odds ratio: 1.23, 95% CI: 0.514-2.95). In
      addition, no significant associations were found between H. pylori infection and
      the various subsets of cancer patients. These findings do not support an
      association between H. pylori infection and non-cardia gastric carcinoma in
      Greece.

PMID- 8280898
TI  - The changing epidemiology of hepatitis A in Italy.
AB  - In 1990, the prevalence of antibodies to hepatitis A virus infection (anti-HAV)
      was assayed by the ELISA method on a national sample of 1000 recruits aged 18-24
      years. The overall prevalence was 29.4% (22.4% in the northern and central
      regions, 32.2% in the south and islands; p < 0.01). Compared with a similar study
      conducted in 1981, the results show a marked reduction in anti-HAV prevalence
      (from 66.3% to 29.4%; p < 0.01). These findings reflect the improved sanitation
      standards in Italy and indicate that the proportion of non-immune adults is
      increasing, with a higher risk of symptomatic infection in the near future.

PMID- 8280899
TI  - Specific pattern of unconjugated bilirubin during fasting can identify
      constitutional hyperbilirubinemia.
AB  - The pattern of individual bilirubin pigments during a 24 hour caloric restriction
      (400 Kcal) was investigated in three groups of patients: one group with
      constitutional hyperbilirubinaemia (n = 29), another with microcytaemia and signs
      of haemolysis (n = 15) and the third consisting of patients without signs of
      hepatic disease (n = 11). The different bilirubin fractions (unconjugated, mono-
      and di-conjugated) were separated as methylated tetrapyrroles by t.l.c. following
      alkaline methanolysis. In all patients fasting induced an enhancement of the
      unconjugated bilirubin while the concentration of mono- and di-methyl esters of
      conjugated bilirubins remained within the normal range. When a pre-fasting
      concentration of total bilirubin equal to 1.2 mg/dl was used as a discriminating
      point, two different patterns in the fasting-induced increase in unconjugated
      bilirubin were identified. An increase of more than 1 mg/dl was found in 30
      patients and 28 of these had constitutional hyperbilirubinaemia as diagnosed by
      exclusion of other disorders. The group with an increase of less than 1 mg/dl was
      composed of 25 patients, only one of whom had constitutional hyperbilirubinaemia:
      14 were affected by microcytaemia and 10 were outpatients without signs of
      disease. The "fasting-induced increase in unconjugated bilirubin" has a
      specificity of 78%, a sensitivity of 84% and a positive and negative predictive
      value of 85 and 76%, respectively, for the diagnosis of constitutional
      hyperbilirubinaemia.

PMID- 8280900
TI  - Acute caecal volvulus: report of 22 cases and review of literature.
AB  - The management of 22 patients with acute caecal volvulus is described along with
      a review of literature. The preoperative diagnosis of caecal volvulus was made in
      60 percent of the cases based on clinical findings and plain abdominal
      roentgenograms. Eleven patients had signs of peritonitis either due to gangrene
      or perforation of the caecum. On laparotomy all patients had mobile caecum but
      precipitating factors were not evident in any patient. The authors recommend
      resection and primary end-to-end ileocolic anastomosis in the presence of
      gangrene or perforation of the caecum. In non-complicated cases of caecal
      volvulus, detorsion and caecopexy are preferable because of low mortality,
      morbidity and recurrence rates.

PMID- 8280901
TI  - The schwannoma: an uncommon type of cystic lesion of the pancreas.
AB  - Schwannomas of the pancreas are rare and their number is lower than is usually
      reported in the literature since some were probably neurofibromas. We report a
      further case characterized by cystic feature, clinically mimicking a pancreatic
      pseudocyst. Cystic lesions of the pancreas also comprise the schwannomas, both
      benign or malignant, as has been previously reported and is stressed by the
      present case. Cyst formation characterizes many diseases of the pancreas, both
      neoplastic and not. Difficulties in the differential diagnosis of cysts are
      fortunately reduced by the preponderance of pseudocysts (i.e. non-neoplastic
      cysts) and, among neoplastic ones, of cystadenomas and cystadenocarcinomas. As a
      consequence, uncommon cystic neoplasms are neglected and very often misdiagnosed.
      We reported a case of solitary schwannoma mimicking a pancreatic pseudocyst,
      interesting both because of its rarity and because of its cystic feature which
      was previously reported in the literature but not emphasized.

PMID- 8280902
TI  - Is chronic pancreatitis a primary disease of the pancreatic ducts? A new
      pathogenetic hypothesis.

PMID- 8280903
TI  - Portal-systemic encephalopathy (PSE) after transjugular intrahepatic portal
      systemic stent-shunts (TIPS).

PMID- 8280904
TI  - Nutritional status in liver cirrhosis.

PMID- 8280905
TI  - Nutritional status in cirrhosis: role of bioelectric impedance analysis.

PMID- 8280906
TI  - The experience in the training and organisation of US in Switzerland.

PMID- 8280907
TI  - Light-induced phase shifts and Fos expression in the hamster circadian system:
      the effects of anesthetics.
AB  - In the present study, we examined the effect of administration of anesthetics on
      light-induced phase shifts of the circadian system. This information is of
      critical importance, because many studies of light input to the mammalian
      suprachiasmatic nucleus (SCN) have been performed on anesthetized animals. We
      found that light-induced phase shifts were blocked by all drugs used at
      anesthetic doses. We then determined the effect of two of these agents on light
      induction of Fos-like immunoreactivity in the SCN. We found that the
      administration of sodium pentobarbital prevented light induction of Fos
      expression in the SCN, whereas the administration of urethane did not. These
      results raise cautions about the use of anesthetized animals to answer questions
      about the photic regulation of neuronal activity in the SCN.

PMID- 8280908
TI  - Age, but not pineal status, modulates circadian periodicity of golden hamsters.
AB  - The pineal gland and its hormone, melatonin, have been implicated in the
      regulation of rat circadian rhythmicity. The present study was designed to
      evaluate whether the pineal has a similar role in the hamster, and to clarify
      whether the marked rhythm responses to constant light (LL) previously seen in
      serotonin-depleted hamsters might be attributable to a functional pinealectomy.
      The results demonstrated that young, but not old, hamsters showed loss of the
      circadian wheel-running rhythm (mostly via splitting) in LL, and that young
      hamsters had longer circadian periods in LL than old animals. Neither effect was
      related to the presence of a pineal gland. In LD 14:10 old animals ran much less
      than young animals, regardless of pineal status, and the suppression of running
      by LL was greater in old animals. The activity phase duration was only modestly
      related to age and not to pineal presence. The data support a previous report of
      an age effect on incidence of rhythm splitting and circadian period length, but
      do not support the view that the pineal gland helps modulate circadian
      rhythmicity in the hamster.

PMID- 8280909
TI  - The association between the nocturnal sleep gate and nocturnal onset of urinary 6
      sulfatoxymelatonin.
AB  - The present study investigated the relationship between the time of nocturnal
      onset of urinary 6-sulfatoxymelatonin (aMT6s) secretion, and the timing of the
      steepest increase in nocturnal sleepiness ("sleep gate"), as determined by an
      ultrashort sleep-wake cycle test (7 min sleep, 13 min wake). Twenty-nine men
      (mean age 23.8 +/- 2.7 years) participated. The ultrashort sleep-wake paradigm
      started at 0700 hr after a night of sleep deprivation and continued for 24 hr
      until 0700 hr the next day. Electrophysiological recordings were carried out
      during the 7-min sleep trials, which were then scored conventionally for sleep
      stages. Urinary aMT6s was measured every 2 hr. The results showed that the timing
      of the sleep gate was significantly correlated with the onset of aMT6s secretion.
      These results are discussed in light of the possible role of melatonin in sleep
      wake regulation.

PMID- 8280910
TI  - Entrainability of circadian activity of the mosquito Culex pipiens pallens to 24
      hr temperature cycles, with special reference to involvement of multiple
      oscillators.
AB  - Entrainability of the circadian rhythm of mosquito flight and locomotor activity
      was investigated by giving a 24-hr temperature cycle (28 degrees C for 16 hr, 23
      degrees C for 8 hr) to the free-running rhythm or by shifting the temperature
      cycle. The phase angle difference between the entrained rhythm and the
      temperature cycle depended on the free-running period, but not on the circadian
      phase at which the temperature cycle started. The rhythm transients (advancing or
      delaying) to entrainment depended on phase, but did not depend on either the
      phase or the free-running period for their average speed. We postulate that
      flight and locomotor activity in the mosquito may be controlled by two circadian
      oscillators moving in different directions in response to the temperature cycle.
      It is likely that at least one of the oscillators is diphasic.

PMID- 8280911
TI  - Winter adaptations of male deer mice (Peromyscus maniculatus) and prairie voles
      (Microtus ochrogaster) that vary in reproductive responsiveness to photoperiod.
AB  - Individuals of many nontropical rodent species restrict breeding to the spring
      and summer. Seasonal reproductive quiescence putatively reflects the energetic
      incompatibility of breeding and thermoregulatory activities. However, so-called
      "out-of-season" breeding occurs in virtually all rodent populations examined,
      suggesting that the incompatibility can be resolved. Both reproductive inhibition
      and development of energy-saving adaptations are mediated by environmental
      photoperiod, but some individuals do not inhibit reproduction in short days. In
      order to assess the costs and benefits of winter breeding, the present study
      examined the extent to which male prairie voles (Microtus ochrogaster) and deer
      mice (Peromyscus maniculatus) that maintained summer reproductive function in
      winter-simulated daylengths also maintained summer thermoregulatory adaptations.
      Circadian locomotor activity patterns, basal metabolic rate, capacity for
      nonshivering thermogenesis, nest building, body mass, and daily food consumption
      were compared among short-day (LD 8:16) regressed males, short-day (LD 8:16)
      nonregressed males, and long-day (LD 16:8) males. Short-day nonregressed deer
      mice resembled long-day conspecifics in terms of body mass and nest-building
      activities; however, the locomotor activity pattern of short-day nonregressed
      deer mice was similar to that of their short-day regressed conspecifics. Short
      day nonregressed prairie voles had body masses similar to those of long-day
      conspecifics. Regardless of their reproductive response to photoperiod, short-day
      prairie voles reduced their daily food consumption and wheel-running activity,
      compared to long-day voles. These results suggest that winter breeding has
      energetic costs, most likely resulting from maintaining a "summer-like" body mass
      relative to that of reproductively regressed animals. These costs may be
      ameliorated to some extent by the reduction in locomotor activity and nest
      building behavior emitted by short-day animals, regardless of reproductive
      response to short days. Thus, the occurrence of winter breeding may be the result
      of sufficient numbers of reproductively photoperiod-nonresponsive morphs in the
      population and sufficiently mild ambient conditions to permit survival of these
      larger animals.

PMID- 8280912
TI  - Pinealectomized rats entrain and phase-shift to melatonin injections in a dose
      dependent manner.
AB  - Previous work has shown that daily injections of the pineal hormone melatonin (N
      acetyl, 5-methoxytryptamine) entrain the free-running locomotor rhythms of rats
      held in constant darkness (with a median effective dose [ED50] of 5.45 +/- 1.33
      micrograms/kg) and in constant bright light. The present experiments determined
      the dose-response characteristics of entrainment and phase shifting to daily and
      single melatonin injections in both sham-operated (SHAM) and pinealectomized
      (PINX) rats. The data indicated an ED50 of 332 +/- 53 ng/kg and 121 +/- 22 ng/kg
      for SHAM and PINX rats, respectively, during the entrainment experiment. The
      ED50's for the entrainment experiment were considerably lower than doses
      previously employed, and much lower than doses employed in reproductive and
      metabolic studies in rats and hamsters. The data indicated that no partial
      entrainment occurred; nor were there differences in phase angle, length of
      activity, or period among all effective doses. Next, a single injection of 1
      mg/kg melatonin has previously been shown to cause a phase advance of
      approximately 45 min when administered at about circadian time (CT) 10. We found
      that both SHAM and PINX animals phase-advanced, in a dose-dependent manner to a
      single melatonin injection given at CT 10. The data for the phase-shifting
      experiment indicated an ED50 of 8.19 +/- 0.572 micrograms/kg and 2.16 +/- 0.326
      micrograms/kg for SHAM and PINX animals, respectively, with an average phase
      advance of 40 min for both groups. Together, the data suggest that the presence
      of the pineal gland is not necessary for the effects of melatonin on the rat
      circadian system, and that PINX animals are marginally more sensitive to
      melatonin than their SHAM controls.

PMID- 8280913
TI  - The ontogeny of circadian rhythms in the rabbit.
AB  - The nursing rhythms of 14 rabbit does and the activity of 18 litters from birth
      to days 14-16 were monitored continuously, as were the circadian rhythms of
      different behavioral functions of 10 young rabbits from weaning until day 380 of
      life. The does gave birth 2 hr, 26 min +/- 2 hr, 8 min after lights-on in a light
      dark cycle (LD 12:12). The first nursing occurred 20 hr, 30 min +/- 2 hr, 21 min
      after parturition. Does that had continuous access to the next boxes exhibited a
      regular once-a-day nursing rhythm; the nursing visits to the litters occurred
      during the dark phase (D). The nursing visits lasted 3 min, 42 sec +/- 25 sec.
      Nursing advanced during the first 10 days of lactation by an average of 42 +/- 16
      min/day, and thus shifted to the first half of D. The pups anticipated nursing by
      a significant increase of activity, which was established between days 1 and 5 of
      life. In two does, the nursing rhythm split into two nursing visits per day, one
      during D and one during the light phase (L). When scheduled to nurse at an
      "artificial" phase in L with T = 24 hr, the pups' anticipatory activity was
      entrained by the 24-hr nursing rhythm. During a 48-hr fast, the elevated activity
      persisted around the phase of prior nursing time, demonstrating that it was
      controlled by an endogenous oscillator entrained by the zeitgeber of maternal
      nursing. Of 10 weanlings, 6 first exhibited a trimodal rhythm, which turned
      bimodal within 3-6 days. Stable entrainment by the external LD zeitgeber was
      attained by about days 45-80, and full nocturnality was attained by about days
      200-250 after weaning. Having attained steady-state conditions, 7 of 10 rabbits
      exhibited a stable unimodal, nocturnal rhythm in each of the five functions,
      while the other 3 retained a bimodal rhythm.

PMID- 8280914
TI  - A curved-field reflectron for improved energy focusing of product ions in time-of
      flight mass spectrometry.
AB  - A new type of curved-field reflectron has been developed for the energy focusing
      of ions formed after initial acceleration in time-of-flight (TOF) mass
      spectrometers. These include ions generated in the dissociation region of a
      tandem TOF, as well as metastable decay products formed in the field-free drift
      region prior to their reflection. Unlike conventional linear-field reflectrons,
      which focus product ions to different focal lengths that are proportional to the
      mass (energy) of the fragment, the new curved-field reflectron energy focuses all
      ions to within a small region near the exit of the reflectron. Thus, the
      collection of resolved fragment peaks is possible without scanning or stepping
      the potential gradient of the reflectron, enabling faster acquisition of the
      production spectrum and, more importantly, true multiplex recording of the
      spectra from each ionization event. Theoretical considerations of the design are
      discussed along with an evaluation of collision-induced dissociation data,
      demonstrating the performance of the new reflectron in a tandem TOF instrument.

PMID- 8280915
TI  - Facile identification by electrospray mass spectrometry of the insulin fragment
      A14-21-B17-30 produced by insulin proteinase.
AB  - We confirm the cleavage at position B16-17 of porcine insulin which occurs during
      in vitro digestion by insulin proteinase. The fragment A14-21-B17-30 was purified
      by reversed-phase high performance liquid chromatography and characterized by
      electrospray ionization mass spectrometry. Fast-atom bombardment mass
      spectrometry, on the other hand, failed to detect the presence of this fragment.

PMID- 8280916
TI  - Multiresidue pesticide analysis by ion-trap mass spectrometry.
AB  - The ion trap has been demonstrated to be able to detect and quantify 245 target
      pesticides extracted via the Luke method while providing concurrent confirmation
      of presence via full scan data at the sub-ppm level. The precision and accuracy
      of the analytical approach was determined to be no greater than 15% relative
      standard deviation. A comparison study of over 100 incurred residues analyzed by
      the ion trap and gas chromatography with an array of element-selective detectors
      has indicated that sample clean-up will probably be necessary before
      quantification is acceptable for all target compounds. The data obtained using a
      combination of gas chromatography and mass spectrometry and presented for 250
      target pesticides constitutes the basic information required to duplicate and
      extend the methodology.

PMID- 8280917
TI  - Characterization of succinimide-type dehydration products of recombinant hirudin
      variant 1 by electrospray tandem mass spectrometry.
AB  - Two congeners Q4 and Q5 inferred in earlier analyses to be cyclic succinimide
      type dehydration products of recombinant hirudin (variant 1) were structurally
      fully characterized. After isotopic labeling by ring-opening with H2(18)O, the
      suspected anhydro-positions Asp53 and Asp33 were confirmed by tandem mass
      spectrometry (MS/MS) sequencing of relevant smaller peptides directly in the
      enzymatic hydrolysates (V8 protease) using electrospray MS/MS. The chosen
      strategy proved highly efficient and sensitive.

PMID- 8280918
TI  - Quantitative analysis of low molecular weight compounds of biological interest by
      matrix-assisted laser desorption ionization.
AB  - Internal standards were used to demonstrate that matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry can be applied to the
      quantitative analysis of low molecular weight polar compounds. Three examples
      were tested: a standard curve for 3,4-dihydroxyphenylalanine (DOPA) was prepared
      using a stable isotope analogue (i.e., [13C6]DOPA) as an internal standard;
      [2H16]-acetylcholine was employed as an internal standard for the quantification
      of acetylcholine; and in the final example, the peptide Ac-Ser-Ile-Arg-His-Tyr
      NH2 was used as an internal standard for the quantification of the peptide H-Ser
      Ala-Leu-Arg-His-Tyr-NH2. In each instance, straight line fits (r2 > 0.95)
      demonstrate that MALDI is a viable approach for the quantitative analysis of low
      molecular weight analytes.

PMID- 8280919
TI  - Direct peptide mapping of sickle-cell hemoglobin using electrospray mass
      spectrometry.
AB  - Direct peptide mapping of sickle-cell hemoglobin (Hb S) using electrospray mass
      spectrometry is demonstrated to be a rapid, sensitive and useful technique for
      providing information concerning the location of variation. By fully comparing
      electrospray mass spectra of digests of sickle-cell and normal hemoglobins, using
      L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK)-treated trypsin, the
      point mutation of B1 fragment of beta-chain in Hb S can be confirmed, taking into
      consideration that all the other fragments are completely identical in the two
      proteins.

PMID- 8280920
TI  - The American Society for Cell Biology 33rd annual meeting. New Orleans,
      Louisiana, December 11-15, 1993. Abstracts.

PMID- 8280921
TI  - VIP gene expression in rat thymus and spleen.
AB  - Vasoactive intestinal peptide (VIP) is a neuropeptide with immunomodulatory
      properties. In the present study, we demonstrate VIP gene expression in cells of
      both thymus and spleen in the rat by in situ hybridization. In thymus sections,
      hybridization signal for VIP mRNA was found in cells in corticomedullary and
      medulla regions. In the spleen, cells were labeled at the outer area on the
      periarteriolar lymphoid sheath of the white pulp. Hybridization signal appeared
      to be in lymphoid cells. These findings suggest that lymphoid cells might produce
      VIP, which, if released, could exert a paracrine action on central and peripheral
      lymphoid organs. We suggest that VIP participates in the bidirectional
      communication between the nervous and the immune systems.

PMID- 8280922
TI  - Depression and immunity: age, severity, and clinical course.
AB  - To begin exploring the relationships between immunity and clinical
      characteristics of depressive disorders and to further investigate the
      association of Major Depressive Disorder with age- and severity-related
      alterations in T lymphocyte numbers and in response to mitogens, we investigated
      53 untreated adult outpatients with DSM III-R Major Depressive Episode (MDE) and
      53 healthy matched controls. The only group difference between MDE patients and
      matched controls was a trend (p < .06) for a decreased number of NK cells in
      depressed subject. In the MDE subjects, increasing age was observed to have a
      significant independent correlation with decreased numbers of total lymphocyte (p
      < .01), B cells (p < .05), and DR+ cells (p < .05) and reduced phytohemagglutinin
      (PHA) (p < .01) and concanavalin A (Con A) (p < .05) mitogen responses. In
      addition, in the depressed subjects there was: (1) an age-independent negative
      correlation between increased duration of the last Major Depressive Syndrome and
      PHA (p < .005), Con A (p < .05), and Pokeweed mitogen (p < .01) responses and (2)
      an age-independent correlation between increased time from the last
      antidepressant medication and total number of lymphocytes (p < .05), T cells (p <
      .05), and NK cells (p = .001). All the above were independent of current life
      habits such as current tobacco, alcohol, and benzodiazepine use. The present
      study suggests that both age at the time of study and clinical characteristics of
      the depressive disorder may be important independent factors in understanding
      psychoimmunological relationships in Major Depression.

PMID- 8280923
TI  - Effects of peripheral cytokine injections on multiple unit activity in the
      anterior hypothalamic area of the mouse.
AB  - The brain and the immune system interact in a bidirectional manner. This study on
      neuroimmune circuitry investigated the hypothesis that circulating cytokines act
      as messengers in the communication from the immune system to the brain and that
      the anterior hypothalamus is an integral part of this pathway. It was predicted
      that, following tail vein injections in mice, the cytokines interleukin-1 beta
      (IL-1 beta), interleukin-2 (IL-2), and interleukin-6 (IL-6) would alter
      electrical activity in the anterior hypothalamus. Differential electrodes were
      used to record multiple unit activity, at 5-min intervals, immediately before and
      for 60 min following injections. IL-1 beta and IL-2 decreased activity in the
      lateral margin of the anterior hypothalamus. IL-2-responsive neurons seemed to be
      localized to this area, while IL-1 beta-sensitive neurons showed a larger area of
      distribution. A significant response following IL-6 administration was not
      demonstrated. The observed changes in electrical activity support the concept of
      the hypothalamus as a sensory integration site for the immune system. Alternative
      models for the mechanism of cytokine signaling are discussed.

PMID- 8280924
TI  - The metabolic stressor 2-deoxy-D-glucose (2-DG) enhances LPS-stimulated cytokine
      production in mice.
AB  - The present study was designed to evaluate the influence of metabolic stress on
      murine cytokine production in vivo. Female Swiss-Webster mice were exposed to a
      single or multiple injections of the metabolic stressor 2-deoxy-D-glucose (2-DG;
      500 mg/kg body wt) once every 48 h and then were injected intravenously with 10
      micrograms of bacterial lipopolysaccharide to stimulate macrophage-derived
      cytokine production. Plasma samples were harvested 2 h later and were assayed for
      interleukin (IL)-1, IL-3, and IL-6 activities using a panel of standardized
      bioassays. It was found that one, two, or three injections of 2-DG enhanced the
      production of all three cytokines. An attenuation of the enhancing effect was
      observed following the fourth and fifth injections. These results demonstrate
      that the metabolic stressor 2-DG can alter immune cell effector functions,
      including the enhancement of normal patterns of cytokine production in vivo.

PMID- 8280925
TI  - Effects of differential housing on the primary and secondary antibody responses
      of male C57BL/6 and BALB/c mice.
AB  - The influence of the number of animals housed together in a cage on antibody
      production in response to keyhole limpet hemocyanin (KLH) was evaluated among
      male C57Bl/6 and BALB/c mice. In Experiment 1, male C57Bl/6 mice were housed 1,
      6, or 12 animals per cage and primary and secondary responses were evaluated. The
      secondary, but not the primary, antibody responses of male C57Bl/6 mice were
      higher among mice housed alone compared to mice housed in groups; differences
      were observed for both IgM and IgG anti-KLH antibodies. The differential housing
      effects on secondary IgM antibody responses interacted with the priming dose of
      KLH. In Experiment 2, the primary and secondary responses to KLH of male C57Bl/6
      and BALB/c mice were compared among mice housed alone or 4 per cage. Among both
      strains, the secondary, not the primary, response was influenced by the number of
      mice housed in a cage; both secondary IgM and IgG titers were higher among the
      C57Bl/6 mice housed alone but only secondary IgM titers were higher among the
      BALB/c mice housed alone. These experiments confirm previous observations that
      the primary antibody responses of C57Bl/6 mice are not influenced by the number
      of animals housed in a cage and extend these findings by demonstrating that the
      secondary antibody responses of C57Bl/6 and BALB/c are influenced by housing
      condition.

PMID- 8280926
TI  - Conditioned enhancement of antibody production using antigen as the unconditioned
      stimulus.
AB  - Antigen is the most salient stimulus for an unconditional activation of the
      immune system. BALB/c mice were given repeated immunizations with keyhole limpet
      hemocyanin (KLH) paired with a gustatory conditioned stimulus (CS). A classically
      conditioned enhancement of anti-KLH antibody titers was observed when conditioned
      mice were reexposed to the CS in the context of reexposure to a minimally
      immunogenic dose of that same antigen. An interaction between signals derived
      from the neuroendocrine and immune systems is hypothesized to mediate this
      conditioned immune response.

PMID- 8280927
TI  - Neonatal sympathetic denervation alters development of natural killer (NK) cell
      activity in F344 rats.
AB  - The development of natural killer (NK) cell activity was assessed in Fischer 344
      (F344) rats sympathectomized as neonates with the neurotoxin, 6-hydroxydopamine
      (6-OHDA). No NK cell activity was detected in sympathectomized or vehicle
      injected control animals at 7 days of age. At 10 and 14 days of age, NK cell
      activity was reduced in spleens from sympathectomized male and female rats. At 21
      days of age, a reduction in NK cell activity was detected only in
      sympathectomized male rats. Sympathectomy did not alter NK cell activity at 28
      and 42 days of age in either gender. At 56 days of age, NK cell activity was
      increased in neonatally sympathectomized females; rats of both genders acutely
      sympathectomized at 56 days of age also showed enhanced NK cell activity. No
      differences were observed at 90 days of age in neonatally or acutely
      sympathectomized males of females. Prior treatment with desipramine, which blocks
      uptake of 6-OHDA into nerve terminals and prevents the destruction of sympathetic
      nerve terminals, prevented these 6-OHDA-induced effects, suggesting that
      sympathectomy, and not direct toxic effects of 6-OHDA treatment of NK cells,
      accounted for the alterations in NK cell activity. Together, these results
      indicate that the sympathetic nervous system is an integral component of the
      developing lymphoid and hematopoietic microenvironment.

PMID- 8280928
TI  - Whither psychoneuroimmunology? A new era of immunology, of psychosomatic
      medicine, and of neuroscience.

PMID- 8280929
TI  - Special issue. The microbiology of Helicobacter pylori. Assessment of recent
      experimental evidence on the pathophysiology, cancerogenic potential, immunity
      and chemotherapy of H. pylori infections.

PMID- 8280930
TI  - Adherence of haemagglutinating Helicobacter pylori to five cell lines.
AB  - Helicobacter pylori causes gastritis and is an important factor for the
      development of peptic ulcer disease in man. We used two different methods to
      examine the adhesion of nine H. pylori strains, with different haemagglutinating
      properties, to five cell lines, HeLa S3, HFI, Vero, SW1222 and WEHI cells. The
      adhesion studies were performed a) as bacterial adhesion to a monolayer of tissue
      culture cells, visualizing bacteria with fluorescein-isothiocyanate-labelled
      antibodies, b) as cell agglutination with bacteria and eucaryotic cells mixed in
      a suspension. The H. pylori strains were divided into three groups according to
      their cell adhesion properties. In general, H. pylori strains which showed the
      best adhesion to the five cell lines were strains which showed the best
      capability of agglutinating erythrocytes of several animal species. It is likely
      that the same adhesins are involved in cell adhesion and in haemagglutination.
      The two methods gave similar results.

PMID- 8280931
TI  - Identification and characterization of Helicobacter pylori phospholipase C
      activity.
AB  - We analyzed 11 H. pylori isolates from humans using the artificial chromogenic
      substrate paranitrophenylphosphorylcholine to detect phospholipase C (PLC)
      activity. The range of PLC in sonicates was 8.8-92.3 (Mean 56.9 +/- 6.5) nmol of
      substrate hydrolysed min-1 mg-1 protein; the amount of activity was not
      associated with urease or cytotoxin levels. Addition of sorbitol or glycerol
      enhanced PLC activity of H. pylori sonicate and purified PLC from C. perfringens
      (PLC1) but not purified PLC from B. cereus (PLC3). H. pylori sonicates had little
      acid phosphatase and no detectable alkaline phosphatase activity, and H. pylori
      PLC showed markedly different biochemical characteristics from either
      phosphatase. In total, these studies indicate that activity measured in H. pylori
      sonicate by PLC assay is due to PLC and not phosphatase activity. The temperature
      optimum for PLC activity of H. pylori sonicate was 56 degrees C and for PLC 1 was
      65 degrees C. For H. pylori PLC and PLC1, optimal activity occurred at pH 8.
      Despite multiple similarities between H. pylori PLC and PLC1, known PLC
      inhibitors show different interactions with each enzyme. Although PLC activity is
      present in many subcellular constituents of H. pylori, including culture
      supernatants and water extracts, highest specific activity is associated with a
      membrane-enriched fraction.

PMID- 8280932
TI  - Siderophore production and iron-regulated envelope proteins of Helicobacter
      pylori.
AB  - All Helicobacter pylori strains tested produced extracellular siderophores,
      detected by a modified Universal Detection medium, but growth on this medium was
      poor. By using the iron chelating compound, 2,2'-dipyridyl, outer membrane
      proteins of 78 and 40 kDa were detected in some, but not all strains examined. No
      direct binding of lactoferrin or transferrin (the mechanism used by Neisseria to
      obtain iron) could be demonstrated for H. pylori. Some other techniques for the
      study of iron-limitation on bacteria were found to be unsuitable for H. pylori.

PMID- 8280933
TI  - Chromosomal heterogeneity of Helicobacter pylori isolates by pulsed-field gel
      electrophoresis.
AB  - The genome of 24 Helicobacter pylori (H. pylori) isolates was analyzed by
      restriction endonuclease digestion and pulsed-field gel electrophoresis (PFGE).
      On PFGE profiles of NotI, 12 isolates among 24 yielded four to nine fragments
      which differed among them. The other 12 isolates could not be digested with NotI.
      The total genome size calculated from individual fragments ranged from 1.04 x
      10(3) to 1.80 x 10(3) kb. This remarkable uneveness in the total genome size
      among isolates is unusual if H. pylori is considered a single species. Therefore,
      the extreme diversity in PFGE profiles and genome size among H. pylori strains,
      which had been considered as homogeneous according to conventional biochemical
      criteria, led us to reexamine the H. pylori species for their genomic homology.
      Furthermore, we used the genetic heterogeneity as a marker to identify specified
      strains among clinical isolates.

PMID- 8280934
TI  - Helicobacter pylori infection within families.
AB  - Although H. pylori is now well established as the aetiological agent of acute or
      chronic gastritis and a predisposing factor in peptic ulceration knowledge
      regarding the transmission of this organism is unclear. The aim of this study was
      to examine the prevalence of H. pylori infection in the family members of index
      children infected with this organism and to examine the role of ethnic background
      and the relationship of hepatitis A infection to H. pylori infection. The H.
      pylori status of three groups of subjects, the family members of 21 children
      shown by endoscopical and histological examination to be infected with H. pylori,
      the family members of 17 children who had been the index case in a hepatitis
      study and a control group of Australian blood donors and children were examined
      using an IgG ELISA. The results of this study showed an increased prevalence of
      H. pylori infection to exist in the family members of index children infected
      with H. pylori compared with the family members of children not infected with H.
      pylori and an age matched blood donor control group. This increased prevalence of
      H. pylori infection was not dependent on ethnic background and appeared to be
      unrelated to the hepatitis A status of subjects. These results strongly support
      the view that transmission of H. pylori is person to person and that transmission
      may not be the faecal oral route.

PMID- 8280935
TI  - Helicobacter pylori and gastric malignancy.

PMID- 8280936
TI  - Is Helicobacter pylori a causal agent in gastric carcinoma?
AB  - The aim of this study is to clarify the relationship between Helicobacter pylori
      (H. pylori) infection and gastric carcinoma. 94 patients with gastric carcinoma
      and 111 patients with chronic gastritis were involved in this study. They were
      classified into 3 age groups: Group A (40 years and under), Group B (41-59),
      Group C (60 years and over). Serum samples were tested for H. pylori IgG
      antibodies by ELISA and for pepsinogen (PG) by RIA. The ratio of PG I/PG II was
      used as a marker for atrophic gastritis. Results were as follows. In the
      incidence of H. pylori antibodies, there was no significant differences between
      gastric carcinoma and chronic gastritis in any of the groups. In the quantity of
      H. pylori antibodies, there was no significant difference between gastric
      carcinoma and chronic gastritis in any of the groups. The ratio of PG I/PG II was
      significantly decreased in H. pylori positive cases when compared to H. pylori
      negative cases in each group with chronic gastritis and group A and B with
      gastric carcinoma. The ratio of PG I/PG II in gastric carcinoma was significantly
      lower than that of chronic gastritis. As conclusion, from the point of view of
      the prevalence of H. pylori, it is suggested that H. pylori is not a direct
      causal agent in the pathogenesis of gastric carcinoma.

PMID- 8280937
TI  - Serology in Helicobacter pylori infection.

PMID- 8280938
TI  - Immunisation against gastric infection with Helicobacter species: first step in
      the prophylaxis of gastric cancer?
AB  - The discovery of the gastric bacterium, Helicobacter pylori and the demonstration
      of its role in the pathogenesis of gastroduodenal disease, has been one of the
      major microbiological advances in the last decade. Recent demonstration of long
      term infection with this bacterium as a risk factor in gastric carcinoma suggests
      that intervention in a disease of major morbidity and mortality is possible.
      Using a model of Helicobacter infection in mice it has been shown that oral
      immunisation with a sonicate of Helicobacter felis plus the adjuvant cholera
      toxin results in protection against an oral challenge with large numbers of
      viable bacteria. The success of the immunising regimen has been shown to
      correlate with the development of local immunity. Formulation of equivalent safe
      vaccines of H. pylori will make possible the immunisation of children in
      countries such as China, Japan and Columbia and so prevent the establishment of
      long term inflammation and thus significantly reduce the incidence of gastric
      cancer in those societies. This animal model is proposed as a major tool in the
      development of effective oral immunisation.

PMID- 8280939
TI  - Stimulatory effects of Helicobacter pylori on human peripheral blood mononuclear
      cells of H. pylori infected patients and healthy blood donors.
AB  - The ability of 23 different strains of Helicobacter pylori to induce
      proliferative response of human peripheral blood mononuclear cells (PBMC) was
      investigated. All tested strains stimulated the DNA synthesis of PBMC from both
      healthy and H. pylori infected blood donors, but with lower stimulation of PBMC
      of infected donors. Using different bacterial antigen preparations, such as crude
      membranes, cytoplasmic proteins, and urease, a significantly lower induction of
      the proliferative response of PBMC from H. pylori infected than from healthy
      blood donors could also be demonstrated. In contrast to this result the reaction
      to phytohemagglutinin and purified protein derivative of tuberculin was similar
      in both groups. The stimulation pathway was interleukin 2 (IL-2) dependent as
      proved by inhibition of the proliferative response with an alpha-IL-2-receptor
      antibody. Using an antibody against HLA-DR the lymphoproliferation could also be
      blocked showing the importance of the major histocompatibility class II (MHCII)
      complex. Only coincubation of T cells with monocytes plus antigen or with antigen
      preincubated monocytes led to a proliferative response showing the necessity of
      antigen-presenting cells. At least a part of the lymphoproliferative response is
      MHCII restricted as could be shown with H. pylori specific T-cell lines. These
      results and the kinetics of the proliferative response with a maximum at day 7
      suggest that the proliferative response of human PBMC was mainly induced by
      antigens than by a mitogen.

PMID- 8280940
TI  - Role of the systemic cellular immune response in the pathogenesis of Helicobacter
      pylori-associated duodenal ulcer.
AB  - 20 patients colonized by H. pylori (9 with duodenal ulcer, 11 with antral
      gastritis) were examined for the presence of a systemic cellular immune response
      to H. pylori using an in vitro lymphocyte transformation assay. Infiltration of
      the antral mucosa by myelomonocytic cells was assessed by immunohistology as a
      parameter of local cellular immune response. A systemic H. pylori-induced
      cellular reaction could be demonstrated in 11 patients all of whom showed an
      intense myelomonocytic infiltration of the antral mucosa. In this group 7 of 9
      duodenal ulcers occurred. The findings support the hypothesis, that a specific
      cellular immune response might be involved in the pathogenesis of H. pylori
      associated gastritis and duodenal ulcer. A protective role of systemic cellular
      immunity to H. pylori seems rather unlikely.

PMID- 8280941
TI  - Humoral and cellular immunity in HIV positive and HIV negative Helicobacter
      pylori infected patients.
AB  - The prevalence of H. pylori associated gastritis seems to be different in HIV
      positive and HIV negative patients. Therefore a correlation to immunodeficiency
      can be postulated. The histology of gastritis, status of H. pylori infection and
      parameters of humoral and cellular immune response were investigated in 41 HIV
      positive and 47 HIV negative patients, who were subjected to upper endoscopy for
      the evaluation of gastrointestinal symptoms. In HIV positive patients 37% had
      active chronic gastritis against 62% of the HIV negative patients. In 73% of HIV
      positive cases of active chronic gastritis H. pylori was detected by
      bacteriological culture and/or Warthin-Starry stain. In HIV negative patients
      active chronic gastritis was always associated to H. pylori infection. Production
      of antibodies as measured by two commercially available ELISA tests was
      significant in HIV positive and HIV negative patients; both tests correlated well
      with H. pylori detection by culture or direct microscopy. Immunoglobulin class
      specific immunoblots corresponded to the ELISA results in HIV negative patients
      but to a lesser extent in the HIV positive group which was assumed to be related
      to unspecific polyclonal activation in these patients. Systemic cellular immunity
      was investigated by proliferation assays of peripheral blood mononuclear cells
      (PBMC). Proliferative response to the unspecific mitogen PHA was reduced in HIV
      positive patients. A sonicated H. pylori antigen failed to induce lymphocyte
      proliferation. The antimitogenic effect was also seen in case of coincubation
      with PHA. This observation was independent of H. pylori and HIV infection status.
      We conclude that in HIV positive as in HIV negative patients active chronic
      gastritis is predominantly related to H. pylori infection. The prevalence of H.
      pylori associated gastritis in HIV positive patients is significantly reduced (p
      < 0.025) compared to HIV negative controls. Decreased susceptibility to H. pylori
      infection in HIV positive patients may not be explained by the abnormal
      reactivity of their humoral or cellular immune response.

PMID- 8280942
TI  - Neutralising antibodies to the vacuolating toxin of Helicobacter pylori in
      gastritis only and peptic ulcer patients.
AB  - Sera from 36 patients with gastritis only and 26 patients with peptic ulcer were
      tested for the presence of neutralising antibodies against H. pylori vacuolating
      toxin. The frequency with which sera did neutralise the vacuolating toxin was not
      significantly different among the groups of patients with gastroduodenal ulcer
      infected either with toxigenic or nontoxigenic H. pylori strains (9/14 vs 4/12;
      ns) or in patients with gastritis only harbouring toxigenic H. pylori strains
      (8/12). By contrast, none of 24 sera obtained from patients with gastritis and
      harbouring non-toxigenic H. pylori strains did neutralise the vacuolating toxin.
      It is suggested that H. pylori vacuolating toxin is involved in the pathogenesis
      of peptic ulcer disease.

PMID- 8280943
TI  - Performance of Helicobacter pylori acid extract and urease enzyme-linked
      immunosorbent assays in relation to 14C-urea breath test.
AB  - The 14C-urea breath test has been shown to be a reliable non-invasive method to
      detect the presence or absence of H. pylori infection. Alternatively, a number of
      techniques have been devised to detect circulating antibodies against H. pylori
      in serum, the most commonly used being enzyme-linked immunosorbent assays
      (ELISA). In the present study we compared the value of two ELISA antigen
      preparations, an acid glycine extract and a urease preparation, in relation to
      the results achieved in a 14C-urea breath test. Seventy-five gastroenterology
      outpatients were screened for the presence of H. pylori infection using the urea
      breath test. At the same time serum specimens were obtained. Thirty-seven
      patients had a positive breath test, i.e. they expired more than 2% of the oral
      14C test dose within 60 min. Using the breath test as reference, sensitivity and
      specificity for the acid extract were 89.2% and 84.2% respectively, and for the
      urease ELISA 81.1% and 89.5%. Agreement between the two ELISAs was found in
      82.7%, overall agreement between all three tests was observed in 77.3%. All three
      tests were found to be useful for monitoring therapy directed against H. pylori.

PMID- 8280944
TI  - Helicobacter pylori antibodies in sera of children suffering from chronic
      abdominal pain.
AB  - 107 pediatric patients aged 9 to 18 with persistent gastric complaints were
      examined serologically and bacteriologically for Helicobacter pylori.
      Helicobacter was identified in 48 (45%) of individuals. 51 (48%) of children were
      found to be seropositive when H. pylori antibodies were detected by the ELISA; 56
      (52%) when the passive haemagglutination test was used, and 41 (38%) in the latex
      agglutination test. 25% of culture-negative patients were found to be
      seropositive. The percentage of raised H. pylori antibody titres in the control
      (healthy subjects) varied from 20 to 27%, depending on the method applied.

PMID- 8280945
TI  - Comparison of four second generation kits for detection of IgG antibodies against
      Helicobacter pylori in adults.
AB  - Four serological kits for detection of IgG antibodies against H. pylori were
      tested on 132 adult patients with dyspeptic symptoms. Presence of H. pylori
      infection was established when either culture or microscopy of gastric biopsies
      were positive. The prevalence of H. pylori infection was 55% in the test
      population. With Anti-H. pylori MTP-assay (Roche), Pylori stat test kit
      (Whittaker), HM-CAP (Enteric Products Inc.) and Pyloriset EIA-G (Orion) the
      sensitivities were 97%, 95%, 81% and 68% respectively, the specificities were
      53%, 56%, 71% and 69% respectively, the positive predictive values 72%, 74%, 79%
      and 74% respectively and the negative predictive values were 94%, 92%, 79% and
      64% respectively.

PMID- 8280946
TI  - In vitro susceptibility testing of Helicobacter pylori to antimicrobial agents:
      basis for treatment or microbiologists' obsession?

PMID- 8280947
TI  - Antibacterial activity of teprenone, a non water-soluble antiulcer agent, against
      Helicobacter pylori.
AB  - Teprenone, a non water-soluble antiulcer agent, is a derivative of terpene. The
      antibacterial activity of teprenone against Helicobacter pylori was examined by
      the disc method and survival test in albumin broth including teprenone. Growth of
      H. pylori around the disc charged with teprenone was inhibited on Brucella agar
      supplemented with bovine serum albumin fraction V, charcoal, or beta-cylodextrin,
      but not with blood or egg yolk emulsion. Furthermore, when H. pylori was exposed
      in broth including teprenone, H. pylori did not survive after 20 hours at 0.25
      approximately 10 ppm. These results indicate that teprenone has antibacterial
      activity against H. pylori.

PMID- 8280948
TI  - Therapeutics used to alleviate peptic ulcers inhibit H. pylori receptor binding
      in vitro.
AB  - Treatment with bismuth-containing remedies has been long associated with the
      alleviation of minor gastric ailments. Bismuth salts have a potent antimicrobial
      activity, and are part of the current standard regime used to treat Helicobacter
      pylori infection. H. pylori is considered to be the major etiological factor in
      the development of peptic ulcer disease. Earlier efficacious treatments for
      peptic ulcer included the oral administration of Tween detergents. We have found
      that these agents have an inhibitory effect on H. pylori adhesion to the lipid
      species phosphatidylethanolamine (PE) and gangliotetraosylceramide (Gg4) shown
      previously to be receptors for H. pylori binding in vitro. H. pylori binding to
      PE and Gg4 was inhibited after a thirty minute preincubation with different
      bismuth compounds: bismuth subsalicylate > bismuth subgallate > bismuth carbonate
      > colloidal bismuth subcitrate > tripotassium dicitrato bismuthate. No inhibitory
      effect on H. pylori binding was observed when bismuth salts were added directly
      into the binding assay. No changes in bacterial morphology and motility were
      observed after the thirty minute incubation. Pretreatment with Tween detergents
      also inhibited H. pylori receptor binding by up to 80% at concentrations as low
      as 0.0001%. These results suggest that inhibition of H. pylori/host cell adhesion
      might play a role in efficacious treatment for this infection.

PMID- 8280949
TI  - Effects of substances inhibiting or uncoupling respiratory-chain phosphorylation
      of Helicobacter pylori.
AB  - The effects of electron transport inhibitors and uncoupling agents as well as of
      bismuth compounds on the respiratory activity and oxidative phosphorylation of
      Helicobacter pylori were investigated. Bismuth gallate and bismuth subsalicylate
      reduced the respiratory chain-dependent phosphorylation. Inhibition was of the
      same magnitude as that observed with other known inhibitors. It is concluded that
      bismuth displays an antibacterial effect by inhibiting the respiratory chain of
      H. pylori.

PMID- 8280950
TI  - Coccoid like forms (CLF) of Helicobacter pylori. Enzyme activity and
      antigenicity.
AB  - In this study we attempted to transform "helical" forms of Helicobacter pylori to
      "coccoid like forms" (CLF) by induction with the following substances in vitro:
      bismuth subcitrate, bismuth subsalicylate, ampicillin, amoxicillin, erythromycin,
      ursodeoxycholic acid and glycochenodeoxycholic acid. Some liquid cultures were
      incubated for 24 days to induce CLF by aging. Changes in the protein pattern,
      urease enzyme activity and in the serological response against specific antigens
      were investigated. In all strains a significant but strain-variable rate of CLF
      was detected by induction of the tested substances. Beta-lactams and erythromycin
      generated a population of nearly 100% CLF, including many "spheroblasts".
      Relative induction rates by these substances were in the following order: beta
      lactams and erythromycin > bismuth subcitrate > bismuth subsalicylate > bile
      acids. Strain variable reaction also was true for both inhibition of urease
      activity and influence on immunological response. Urease activity was lost in CLF
      induced by aging and was inhibited by bismuth salts. CLF induced by aging showed
      a loss of reactivity bands in the immunoblot. They always lost a 160 kD band and
      depending on the strain, 115 kD, 108 kD, 100 kD and 95 kD bands. Immunological
      response to the 120 kD band was reduced. Ultrastructural studies showed great
      degenerative changes of the cell wall in CLF induced by antibiotics but only few
      in CLF induced by bismuth salts and bile acids.

PMID- 8280951
TI  - Influence of omeprazole on urease activity of Helicobacter pylori in vitro.
AB  - The influence of omeprazole on urease activity of 13 Helicobacter pylori strains
      was assessed in vitro employing different inocula of the bacteria and various
      concentrations of omeprazole. Bacteria were grown in liquid culture supplemented
      with omeprazole for 48 h. Afterwards, bacterial numbers were assessed and urease
      activity was measured in a spectrophotometric assay. In 10 strains, omeprazole
      had no influence on urease activity at concentrations up to 8 mg/l; higher
      concentrations had a bacteriostatic effect. Three strains were more resistant to
      omeprazole: These showed a marked diminution of urease activity although
      bacterial numbers were only slightly reduced. Thus a possible inhibitory effect
      of omeprazole should be taken into account when urease of Helicobacter pylori is
      measured for diagnostic purposes.

PMID- 8280952
TI  - Activity of antibiotics and azole antimycotics against Helicobacter pylori.
AB  - The bacteristatic and bactericidal activities of six antibiotics from different
      substance classes against Helicobacter pylori were determined. Ampicillin,
      imipenem, tetracycline, and amikacin inhibit the growth of all isolates at
      concentrations achievable in serum. Cefpirome and ofloxacin are ineffective
      against three and two of 41 strains, respectively. However, the minimum
      bactericidal concentrations (MBC) of the substances are two- to sixteen-fold
      higher than the minimum inhibitory concentrations (MIC). There is sufficient
      bactericidal activity of ampicillin and imipenem against all strains, but
      amikacin, ofloxacin, tetracycline, and cefpirome are unable to kill 2, 8, 12, and
      18 of 25 strains, respectively, at concentrations achievable in serum.
      Differences between MIC and MBC of antibiotics may contribute to the explanation
      of therapy failures. In addition, the inhibitory activity of seven nitroimidazole
      antimycotics and the triazole fluconazole was evaluated. The nitroimidazole MICs
      range from 2 to 64 mg/l, with tioconazole, miconazole, bifonazole, and
      ketoconazole as the most active substances. Fluconazole, however, was ineffective
      at concentrations < or = 128 mg/l. The efficacy of the nitroimidazole
      antimycotics against H. pylori in vivo should be tested in a clinical trial.

PMID- 8280953
TI  - Animal models of bacterial gastritis: the role of host, bacterial species and
      duration of infection on severity of gastritis.
AB  - Gastric bacteria from cheetahs with gastritis were used to inoculate specific
      pathogen free kittens and conventional mice. Helicobacter sp. and Gastrospirillum
      sp. colonized kittens, while only Gastrospirillum sp. colonized mice. In kittens,
      both bacterial species induced mild lymphofolliclar gastritis which did not
      change over the course of the 11 months observation period. In mice,
      Gastrospirillum sp. induced lymphoplasmacytic and follicular gastritis which
      increased in severity over 6 months and persisted for the 12 month observation
      period. Gastric ulcers and gastric mucosal hypertrophy were present in
      chronically infected mice. These results indicate that host but not bacterial
      factors influence the severity of gastritis, and that in mice, bacterial
      gastritis increases in severity with time and may lead to gastric ulceration in
      some individuals.

PMID- 8280954
TI  - Prevalence of Helicobacter pylori in gastrointestinal disorders and
      concentrations of ciprofloxacin in serum and gastric mucosa.
AB  - Endoscopic antral biopsies were obtained from 30 patients with several
      gastrointestinal disorders and analysed for the presence of H. pylori. This
      bacterium was present in 80% and 58%, respectively, of patients with either
      gastric and duodenal ulcers and gastric neoplasm. In none of the healthy
      individuals, H. pylori could be found. Another 14 patients with various diseases
      of the stomach, undergoing a major gastric resection, had been treated with 200
      mg ciprofloxacin intravenously immediately before the operation. Blood and
      various tissues samples were taken during the operation. The prevalence of IgG
      antibodies against H. pylori in these patients was 93%. H. pylori could be
      determined in 71% of the cases by the urease production; by culture, this was
      possible in only one case. The mean peak concentration of ciprofloxacin in serum
      was 5.31 mg/l and 1.17 mg/l, respectively, immediately and 60 min after the end
      of infusion; in tissues of antrum and duodenum, 1.59 to 1.64 mg/kg and 1.41 to
      1.72 mg/kg, respectively, 45-270 min after the infusion. The results show that
      ciprofloxacin rapidly penetrates into tissues and attains concentrations greater
      than the MIC90 for H. pylori. However, these concentrations can inhibit the
      isolation of this microorganism but not its urease activity. This fact could be
      interpreted by the existence of a nonculturable but metabolically active form of
      H. pylori. This would explain the high rate of recrudescence following most types
      of currently applied therapeutic schemes.

PMID- 8280955
TI  - Long term infection of the gastric mucosa with Helicobacter species does induce
      atrophic gastritis in an animal model of Helicobacter pylori infection.
AB  - Gastric atrophy is a precursor lesion in the development of gastric cancer. It
      has been proposed that atrophy is part of a natural progression of inflammatory
      changes that result from long term infection with the bacterium Helicobacter
      pylori. The aim of this study was to test this hypothesis using an animal model
      of human Helicobacter infection. Conventional mice were infected with either a
      cat isolate of Helicobacter felis or a human isolate of "Gastrospirillum
      hominis". All infected mice showed a slowly progressive chronic gastritis with
      increasing numbers of infiltrating mononuclear cells and polymorphonuclear
      leucocytes. After a year and a half, the inflammatory reaction was so severe that
      atrophic changes were seen in both the antral and fundic mucosa. Control animals
      initially showed no inflammatory changes however as the animals aged, the gastric
      mucosa of some animals became infected with a bacterium Helicobacter muridarum
      that normally inhabits the small and large bowel of the rodent. The presence of
      this bacterium was also associated with gastritis and atrophic changes. This is
      the first report of experimentally induced atrophic changes induced by a gastric
      bacterium and opens the way for important experiments that will help better
      understand the induction of gastric cancer.

PMID- 8280956
TI  - Discovery of "curved bacilli" in the stomach.

PMID- 8280957
TI  - Serial change of gastric mucosa after challenging with Helicobacter pylori in the
      cynomolgus monkey.
AB  - The aim of this study was to clarify the change of the gastric mucosa following
      inoculation with Helicobacter pylori (H. pylori). Two pairs of cynomolgus monkeys
      received either H. pylori of human origin (group A) or H. pylori of monkey origin
      (group B) by intragastric inoculation at a dose of 10(9) CFU. After inoculation,
      endoscopical observation and biopsies were done every 7 days for one month. The
      bacteria in the biopsy samples were cultured quantitatively. The content of
      intracellular PAS-AB positive substance was quantitatively analyzed with the
      image analyzing system. Results were as follows: 1) Before inoculation, the
      gastric mucosa was endoscopically normal and free from H. pylori. 2) The quantity
      of H. pylori varied from 0 to 10(3) CFU/0.1 g tissue in group A and from 10 to
      10(6) CFU/0.1 g tissue in group B. 3) Severe erosion was seen in group B, while
      mild mucosal erythema and erosion were observed in group A. 4) There was a
      correlation between the quantity of H. pylori and histological activity (Rauws'
      gastritis score). 5) The PAS-AB positive substance in H. pylori-positive mucosa
      was less than that in H. pylori-negative mucosa. In conclusion, gastric mucosal
      changes of varying degrees were brought about after inoculation of H. pylori
      depending on the quantity of bacilli in the gastric tissue.

PMID- 8280958
TI  - Interaction of Helicobacter pylori (strain 151) and Campylobacter coli with human
      peripheral polymorphonuclear granulocytes.
AB  - Helicobacter pylori associated gastritis is characterized by dense mucosal
      inflammatory infiltrations with predominantly neutrophilic granulocytes, together
      with a local and systemic immune response. Nevertheless, the natural course of
      the infection is chronic in nature, and active phagocytosis of H. pylori by
      mucosal granulocytes was only rarely observed. The aim of the present study was
      to investigate with electronmicroscopic methods the interaction of H. pylori with
      freshly harvested human peripheral granulocytes, with Campylobacter coli as
      control organism. Bacteria, either untreated or opsonized with complement or
      antiserum, were coincubated with phagocytes for up to 120 min. After defined time
      periods the following parameters were electronmicroscopically evaluated: i)
      internalization of bacteria., ii) morphological characteristics of bacteria and
      phagocytes, iii) decrease of lysosomes, and iv) by use of myeloperoxidase
      staining, the characteristics of phagolysosomal fusion. In the absence of
      complement, both organisms were internalized to a comparable extent. However, in
      contrast to C. coli, remarkable amounts of H. pylori cells remained
      extracellularly attached even after 120 min of coincubation, as well as
      internalized bacteria remained morphologically largely unimpaired. If complement
      was present, internalization and morphological destruction of H. pylori cells
      were significantly enhanced. The latter was characterized by rounding and
      swelling of H. pylori cells. It was already apparent in the extracellular space,
      and therefore probably induced by a complement effect, rather than by tee
      phagocytic action. Decrease of lysosomes, in general paralleled the degree of
      microbial uptake. Myeloperoxidase staining experiments furthermore showed an
      obviously regular consumption of lysosomal granules. However, if complement
      opsonization was excluded, lysosomal degranulation was not accompanied by a
      corresponding degradation of H. pylori cells, the latter indicating an at least
      partial resistance to phagocyte caused microbicidal mechanisms. In most of those
      cases ingested H. pylori cells were, in contrast to C. coli, surrounded by a
      rather "tight" phagosome. A possible explanation for this phenomenon could be a
      "leakage" of the phagosomal membrane, possibly caused by membranotoxic ammonia
      produced by the organism. If such an impairment of the phagocytic action would
      occur in vivo, it could lead to an impaired cellular defense, and therefore
      contribute to the chronic course of H. pylori infections.

PMID- 8280959
TI  - The evangelism of Helicobacter pylori: how to convince the non-believers and curb
      the believers.

PMID- 8280960
TI  - In situ localization of the 60 k protein of Helicobacter pylori, which belongs to
      the family of heat shock proteins, by immuno-electron microscopy.
AB  - The groEl homologue of Helicobacter pylori was isolated and characterized by
      means of immunoelectron microscopy, after cryosectioning. The 60 k protein was
      isolated from Helicobacter pylori by treatment of the cells with 2-butanol and
      purified by anion exchange chromatography. The native molecular weight of the 60
      k protein was estimated to be 420 k by size exclusion chromatography. The
      purified 60 k protein showed the typical rotational symmetry of chaperonins when
      analyzed by electron microscopy. Ultrathin sections of Helicobacter pylori were
      immunostained by a polyclonal antibody directed against the hsp-65 of
      Mycobacterium tuberculosis. The label revealed a clustered localization of the 60
      k protein on the cell surface as well as in the periplasmic space.

PMID- 8280961
TI  - Activation of human phagocytes by Helicobacter pylori. A novel interaction with
      neutrophils and monocytes distinct from that of N-formylated oligopeptides.
AB  - Sonicate proteins from Helicobacter pylori activate human neutrophils and
      monocytes for chemotactic and oxidative burst responses. The molecular nature of
      this activity and its interaction with the phagocyte membrane is unknown. Cross
      stimulation experiments were performed with human neutrophils and monocytes
      preincubated in H. pylori sonicate and subsequently stimulated with the
      established and characterised stimuli N-f-methionyl-leucyl-phenylalanine (fMLP),
      the complement split product C5a (in zymosan-activated serum, ZAS), and phorbol
      myristate-acetate (PMA). Checkerboard experiments confirmed the sonicate to be
      truly chemotactic, whereas no chemokinetic activity was demonstrated. At high
      concentrations of sonicate (1 mg/ml), a depressed chemotactic and oxidative burst
      response was observed, whereas the viability was > 98%. At lower concentrations
      (0.01-0.1 mg/ml), only weak deactivation could be induced for monocytes, i.e. the
      cells had a normal function. With neutrophils, even low concentrations of
      sonicate depressed the oxidative burs responsiveness. However, the reduced
      activity was unrelated to the stimulus applied indicating that H. pylori
      protein(s) activate human neutrophils and monocytes by a membrane binding site
      distinct from that of previously described receptors.

PMID- 8280962
TI  - Effect of war-induced prolonged stress on cortisol of persons with type II
      diabetes mellitus.
AB  - The study was designed to assess the impact of protracted, war-induced stress on
      cortisol levels and glycemic control in persons with Type II diabetes mellitus. A
      randomly selected sample of 44 displaced Type II diabetic persons was compared
      with a group of diabetic persons matched for sex, age, weight, duration of
      diabetes, and type of treatment who had not been forced to leave their homes. The
      self-reported stress, depression level, serum cortisol, fasting blood glucose,
      and glycosylated hemoglobin were compared. The two groups were found to be
      significantly different in scores for self-reported stress and depression level.
      Passive coping patterns prevailed in the displaced group. The serum cortisol
      levels correlated positively with self-reported stress, negatively with active
      coping patterns, and were significantly higher in the displaced persons group. No
      significant differences were found between the group on the variables measuring
      glycemic control. The results indicate that prolonged stress need not worsen
      glycemic control in Type II diabetic patients.

PMID- 8280963
TI  - Invasiveness of medical procedures and state anxiety in women.
AB  - The authors studied state anxiety in women awaiting three different medical
      examinations: abdominal ultrasonography, mammography, and hysterosalpingography.
      These procedures differ in degree of intrusiveness and cause, respectively, low,
      intermediate, and high levels of pain and discomfort. The evidence supported the
      hypothesis that the degree of anxiety will correspond to the level of
      invasiveness. In addition, the study examined the impact of demographic variables
      on degree of anxiety. The results suggest that to plan appropriate strategies for
      stress reduction, the medical team treating women should be aware of the degree
      of the procedure's invasiveness.

PMID- 8280964
TI  - A review of studies comparing checklist and interview methods of data collection
      in life event research.
AB  - This article is concerned with the relative merits of checklists and interviews
      as techniques for collecting data in the study of life events. It presents a
      detailed review of studies that have directly compared checklists and interviews.
      The author's conclusion is that the two techniques should not be seen as
      equivalent in the assessment of life events. Virtually all of the studies
      reviewed showed a marked tendency to overreport on checklists. The method appears
      inadequate in distinguishing truly stressful events from trivial occurrences. In
      contrast, the in-depth interview is sensitive to the subtleties of life events
      and should be the preferred method when data of any precision and accuracy are
      required in an empirical study.

PMID- 8280965
TI  - Organizational characteristics, perceived work stress, and depression in
      emergency medicine residents.
AB  - A structural equation analysis of data collected from 484 members of the
      Emergency Medicine Residents Association was used to test a model in which peer
      support and work-group cohesiveness predicted role ambiguity. Role ambiguity was
      then specified as a predictor of work-related stress. Stress was hypothesized to
      affect depression and work satisfaction. The analysis confirmed the direct
      relationship between stress and depression and indicated that support from peers
      and the work group reduces stress. This impact is influenced by the amount of
      role ambiguity perceived by residents. Peer support, role ambiguity, and stress
      explain 52% of the variance in depression reported by residents. Residents are
      more satisfied with their work when their peers are supportive and when levels of
      occupational stress and role ambiguity are not high. The model accounted for 47%
      of the variance in reported work satisfaction. The results suggest that role
      ambiguity leads to perceptions of stress. This perceived stress, in the absence
      of strong support groups, results in increased depressive symptomatology and
      decreased work satisfaction.

PMID- 8280966
TI  - Personality characteristics of chronic bruxers.
AB  - One hundred twelve adults randomly selected from a periodontal practice
      participated in research to determine whether the personality traits of people
      who chronically brux (grind their teeth) diverge significantly from the
      personality traits of those who do not do so. All participants completed a
      personality questionnaire and were examined by the periodontist, who determined
      which were chronic bruxers. Twenty-eight of the men and 46 of the women were
      diagnosed as bruxers. Their personality trait scores differed significantly from
      those of the nonbruxers. In general, and regardless of gender, chronic bruxers
      were found to be shy, stiff, cautious, and aloof, preferring things rather than
      people, avoiding compromises, rigid in their ways, affected by feelings of
      inferiority, impeded in expressing themselves, apprehensive, and given to
      worrying.

PMID- 8280967
TI  - MR site accreditation.

PMID- 8280968
TI  - Pulse sequence strategies for vascular contrast in time-of-flight carotid MR
      angiography.
AB  - A systematic evaluation in healthy volunteers of the relative efficacy of various
      techniques for background suppression to improve two-dimensional (2D) and three
      dimensional (3D) time-of-flight magnetic resonance angiography of the cervical
      carotid arteries was performed. Conventional 2D and 3D FISP (fast imaging with
      steady-state precession) sequences with flow compensation were compared with
      modifications of these sequences, including a tracking saturation pulse (2D),
      prolonged absolute TEs for fat suppression based on T2* decay (2D and 3D),
      frequency-selective saturation of fat (2D and 3D), in-plane spatial saturation
      (2D), and magnetization transfer contrast (2D and 3D). The tracking saturation
      pulse and slight overlap of the excitation sections provided uniform background
      suppression without impairing depiction of the morphology of the cervical carotid
      arteries. Frequency-selective fat saturation was the most effective background
      suppression scheme among the 2D and 3D techniques but was occasionally
      compromised by local field inhomogeneities. Magnetization transfer contrast
      provided little suppression of stationary tissues in the neck because of the
      intrinsic limitations of the coil. In-plane spatial saturation yielded the
      highest background suppression but reduced apparent arterial diameters and could
      not be implemented in a 3D version. The T2* decay method not only reduced the
      apparent size of the vessels but also their signal intensity.

PMID- 8280969
TI  - Gadolinium phosphonates as MR imaging contrast agents: physiologic effects in
      rabbit hearts.
AB  - The hemodynamic effects of the diphosphonate terminus of a new infarct-avid
      magnetic resonance (MR) imaging agent, gadolinium-DTPA (diethylenetriamine
      pentaacetic acid) HPDP (1-hydroxo-3-aminopropane-1,1-diphosphonate), and HEDP
      (hydroxyethyl-1,1-diphosphonate) (a simple diphosphonate terminus model) have
      been evaluated at MR imaging doses in both isolated and intact rabbit hearts.
      Rapid injections of the sodium salt of the diphosphonates reversibly depressed
      left ventricular developed pressure and its first derivative (dP/dt) but did not
      affect the in vivo heart rate. Hemodynamic depression was prevented by the co
      administration of two equivalents of calcium ion per diphosphonate terminus in
      the isolated heart and by either slow infusion or co-administration of one
      equivalent of calcium ion per diphosphonate terminus in the in vivo heart.
      Therefore, if these agents are to be used in MR imaging of acute myocardial
      infarction, appropriate measures should be taken to prevent negative inotropic
      effects.

PMID- 8280970
TI  - Aortoiliac disease: two-dimensional inflow MR angiography with lipid suppression.
AB  - A magnetic resonance (MR) imaging strategy, SLIP (spatially separated lipid
      presaturation), which can be incorporated into existing MR imaging and MR
      angiographic techniques, has been developed to suppress lipid signal. The authors
      report the clinical application of this technique, with a triple comparison of
      two-dimensional inflow MR angiography, with and without SLIP, and x-ray
      angiography in patients with aortoiliac disease. SLIP improved visualization of
      arterial segments, with 50 of 63 (79%) arterial segments visualized versus 41 of
      63 (65%) for non-SLIP MR angiography. The SLIP strategy aids in the depiction of
      slow or turbulent flow, because the lipid signal is suppressed while the
      intravascular signal is left undisturbed. Image quality improves because of the
      combination of decreased background lipid signal intensity and use of the maximum
      intensity-projection algorithm. Compared with x-ray arteriography, non-SLIP MR
      angiography had a sensitivity and specificity of 60% and 56%, respectively, for
      detection of lesions with 50%-100% diameter reduction, while SLIP MR angiography
      had a sensitivity and specificity, respectively, of 53% and 67%.

PMID- 8280971
TI  - Fast spin-echo imaging of the knee: factors influencing contrast.
AB  - Conventional T2-weighted spin-echo magnetic resonance imaging of the knee
      requires a long TR. Fast spin-echo (FSE) imaging can improve acquisition
      efficiency severalfold by collecting multiple lines of k space for each TR.
      Compromises in resolution, section coverage, and contrast inevitably result. The
      authors examined the compromises encountered in FSE imaging of the knee and
      discuss the variations in image contrast and resolution due to choices of
      sequence parameters. For short TR/TE knee imaging, FSE does not appear to offer
      any advantages, since the increased collection efficiency for one section reduces
      the available number of sections, so that the total imaging time for a given
      number of sections remains constant relative to conventional spin-echo imaging.
      For T2-weighted images, considerable time can be saved and comparable quality
      images can be obtained. This saved time can be usefully spent on increasing both
      the resolution of the image and its signal-to-noise ratio, while still reducing
      total acquisition time by a factor of two. The preferred FSE T2-weighted images
      were acquired with a TR of 4,500 msec, TE of 120 msec, and eight echoes. The
      available number of sections is compromised, and the sequence remains sensitive
      to flow artifacts; however, the FSE sequence appears to be promising for knee
      imaging.

PMID- 8280972
TI  - MR imaging of patellar retinacular ligament injuries.
AB  - Seventeen patients with patellar retinacular ligament injuries were evaluated
      with magnetic resonance (MR) imaging. MR findings were correlated with clinical,
      surgical, and arthroscopic findings. The injuries involved the medial retinacular
      ligament in 16 of 17 patients and the medial and lateral retinacular ligament in
      one patient. Nine of 17 patients showed MR evidence of a patellar dislocation. In
      these patients, a triad of findings that included focal impaction injuries
      involving the lateral femoral condyle, osteochondral injuries of the medial
      patellar facet, and injuries of the medial retinacular ligament were seen. Seven
      of the nine patients with patellar dislocation injuries had frank osteochondral
      injuries. The injured retinaculum had an indistinct, irregular appearance
      associated with edema and hemorrhage. The patellar dislocations were clinically
      unsuspected in the initial evaluation of eight of these nine patients. In eight
      of 17 patients, the mechanism of injury was a patellar tendon tear (n = 1) or
      valgus hyperextension (n = 7). In the seven patients with hyperextension
      injuries, three had associated meniscal and cruciate ligament tears. MR imaging
      can help define patellar retinacular and associated osteochondral injuries, which
      may be clinically useful information.

PMID- 8280973
TI  - Automated pixel-by-pixel mapping of dynamic contrast-enhanced MR images for
      evaluation of osteosarcoma response to chemotherapy: preliminary results.
AB  - An automated technique for pixel-by-pixel computer mapping of tumor necrosis was
      developed to improve the accuracy and applicability of dynamic contrast agent
      enhanced magnetic resonance (MR) imaging in assessing the response of
      osteosarcoma to preoperative chemotherapy. The technique was evaluated in nine
      osteosarcoma patients who underwent MR imaging at diagnosis (n = 7) and after
      preoperative chemotherapy (n = 9). Sequential FLASH (fast low-angle shot) images
      of the tumor were obtained in one plane every 15 seconds before and for 3 minutes
      after gadopentetate dimeglumine injection. A region of interest was selected that
      included the entire tumor area. Slopes representing percent increase in signal
      intensity over baseline values per minute were calculated automatically for each
      pixel and displayed as gray-scale maps of the tumor. Matching histologic maps of
      each tumor were obtained. Visual region-by-region comparison of the pixel and
      histologic maps showed a high degree of correlation and the ability of the MR
      imaging technique to help identify small foci of residual viable tumor.

PMID- 8280974
TI  - Acute spinal ligament disruption: MR imaging with anatomic correlation.
AB  - Disruption of spinal ligaments can lead to instability that jeopardizes the
      spinal cord and nerve roots. Magnetic resonance (MR) imaging can directly image
      spinal ligaments; however, the sensitivity with which this modality demonstrates
      ligament injury has, to the authors' knowledge, not been reported. On a
      biomechanical testing machine, 28 cadaveric spines were subjected to controlled
      injury that resulted in ligament tears. The spines were then imaged with plain
      radiography, computed tomography, and MR imaging (1.5 T). The images were
      analyzed for evidence of ligament injury before dissection of the specimen. Forty
      one of 52 (79%) ligament tears of various types were correctly identified at MR
      imaging. Disruptions of the anterior and posterior longitudinal ligaments were
      most conspicuous and were detected in all seven cases in which they were present
      (no false-positive or false-negative results); disruptions of the ligamentum
      flavum, capsular ligaments, and interspinous ligaments could also be identified
      but less reliably (three false-positive and 11 false-negative results). That MR
      imaging can reliably and directly allow assessment of spinal ligament disruption
      in this in vitro model suggests its potential utility for this assessment in
      patients.

PMID- 8280975
TI  - Discrimination between different types of white matter edema with diffusion
      weighted MR imaging.
AB  - Brain edema can be classified into three categories: vasogenic, cytotoxic, and
      interstitial. The mechanism of edema is thought to be different in each type. The
      authors studied the movement of water molecules in each type of white matter
      edema in a rat model by using diffusion-weighted magnetic resonance imaging.
      Conventional T2-weighted imaging did not allow distinction between the three
      types of white matter edema; the three types of edema were, however,
      distinguished by using diffusion-weighted imaging. The apparent diffusion
      coefficient (ADC) of water was different in each type of edema. Water molecules
      in cytotoxic edema induced by triethyl-tin intoxication showed a smaller and less
      anisotropic ADC than in normal white matter. In contrast, water in vasogenic
      edema induced by cold injury had a larger and more anisotropic ADC than in normal
      white matter. Water in interstitial edema due to kaolin-induced hydrocephalus had
      an anisotropic and very large ADC.

PMID- 8280976
TI  - Functional mapping of human motor cortical activation with conventional MR
      imaging at 1.5 T.
AB  - A conventional 1.5-T magnetic resonance (MR) imager was used to detect signal
      intensity changes on T2*-weighted images of human motor and sensory cortices
      during performance of hand and tongue movements. Narrow receiver bandwidths were
      used to improve the signal-to-noise ratio. Protocols consisting of baseline,
      motor task, rest, and second motor task periods were performed by nine
      volunteers. Two-dimensional cross correlation was applied to correct in-plane
      translation and rotation of the head during the imaging session before the
      control images were subtracted from the task images. Measurements obtained during
      finger movement tasks indicated a 3%-8% increase in signal intensity near the
      contralateral central sulcus and smaller ipsilateral signal intensity increases.
      Bilateral signal intensity increases were also observed during tongue movement
      studies. A retrospective image registration technique was used to map the signal
      changes onto conventional anatomic images, which were used to create integrated
      three-dimensional models of brain structure and function. These integrated images
      showed that the highest signal intensity due to hand movement was near the
      putative central sulcus.

PMID- 8280977
TI  - Dynamic gadolinium-enhanced three-dimensional abdominal MR arteriography.
AB  - The abdominal aorta and renal, visceral, and iliac arteries were evaluated in 16
      patients with three-dimensional Fourier transform imaging enhanced with
      gadopentetate dimeglumine. By imaging dynamically during the arterial phase of a
      5-minute injection (0.2 mmol/kg), highly significant (P < .0001) preferential
      arterial enhancement (signal-to-noise ratio +/- standard deviation, 10 +/- 0.9),
      with minimal enhancement of the inferior vena cava (5.1 +/- 1.4) or background
      tissues (fat, 4.3 +/- 0.7; muscle, 2.4 +/- 0.5), was achieved in every patient.
      In six patients with angiographic and/or surgical correlation, 10 of 10 stenoses
      and two of two occlusions were correctly identified. No in-plane saturation or
      pulsatility artifact was identified in any of the 16 patients. In conclusion,
      dynamic imaging during the injection of gadopentetate dimeglumine is a promising
      technique for evaluation of the abdominal aorta and branch vessels.

PMID- 8280978
TI  - Statistical description of microcirculatory flow as measured with an MR method.
AB  - Quantification of microcirculatory flow is important for the functional
      assessment of biologic systems. The authors describe a method of analyzing the
      dependence of the magnetic resonance (MR) signal intensity on microcirculatory
      flow. A gel bead phantom was used to simulate the randomly oriented flow
      capillaries, and the MR signal intensity of the phantom was studied at different
      flow velocities by using velocity-sensitized and -compensated spin-echo pulse
      sequences. A theoretical model based on the spin-phase phenomenon is proposed to
      elucidate the effect of flow on signal intensity. The velocity phase of a spin
      depends on its path and the corresponding velocity-encoding gradients. A Monte
      Carlo simulation was used to generate the path of a spin on the basis of a
      statistical model for flow through a random capillary network. From the velocity
      phase distribution of a group of spins within a voxel, the signal attenuation due
      to flow can be calculated. The results of the statistical model and experimental
      measurements agreed well. Also, T1 and T2 effects in MR flow measurements were
      investigated. The current study provides a theoretical framework for
      understanding MR measurements of microcirculatory flow.

PMID- 8280979
TI  - Uterine contractions: possible diagnostic pitfall at MR imaging.
AB  - A total of 206 nongravid patients with various gynecologic problems underwent
      pelvic magnetic resonance (MR) examinations that included both sagittal T2
      weighted and contrast agent-enhanced T1-weighted images. MR images were
      retrospectively reviewed to identify changes in endometrial configuration on
      serial images obtained during the same MR examination. In 20 MR examinations (all
      in women of reproductive age), endometrial distortion due to myometrial bulging
      was noted on T2-weighted or contrast-enhanced T1-weighted images. It was absent
      on other MR images obtained at different times. Myometrial bulging exhibited low
      signal intensity in 18 examinations. The finding resembled adenomyosis or
      leiomyoma on T2-weighted or contrast-enhanced T1-weighted images. These results
      evidence the presence of transient myometrial bulging and transient low-intensity
      myometrium in the nongravid uterus. This phenomenon is thought to represent
      uterine contraction. Clinicians should be aware of the potential presence of
      transient low-signal-intensity myometrial bulging that could present diagnostic
      problems in the normal uterus.

PMID- 8280980
TI  - Three-dimensional fast spin-echo imaging: pulse sequence and in vivo image
      evaluation.
AB  - Three-dimensional (3D) magnetic resonance imaging allows thin-section acquisition
      and therefore more accurate multiplanar reconstruction than conventional two
      dimensional spin-echo imaging. Unfortunately, addition of a third acquisition
      plane extends imaging time greatly. With gradient-echo techniques, 3D
      acquisitions have become clinically useful. These techniques are limited,
      however, by susceptibility and other field inhomogeneity artifacts and decreased
      signal-to-noise ratios compared with spin-echo techniques. The authors describe
      implementation of a true spin-echo 3D technique that, by using fast spin-echo
      parameters, reduces acquisition time to a clinically useful level. Potential
      applications of the technique are demonstrated.

PMID- 8280981
TI  - Two-point interference method for suppression of ghost artifacts due to motion.
AB  - A two-point interference method is introduced for suppression of ghosting due to
      motion in magnetic resonance imaging. The method requires only two time
      interleaved data acquisitions, without any monitoring of the motion. A
      postprocessing technique is used to produce a weighted sum of the two acquired
      images, in which ghosts are suppressed by interference through an automatic
      regional tuning procedure. The appropriate complex weighting factors are
      regionally chosen by minimizing the "gradient energy," which is defined as the
      sum of squared pixel values in the partial-derivative maps. The method was tested
      in both phantoms and volunteers with a variety of imaging protocols. The level of
      ghost suppression with the two-point method was found to be comparable to that of
      the three-point method described previously by the authors.

PMID- 8280982
TI  - Frequency response to retrospectively gated phase-contrast MR imaging: effect of
      interpolation.
AB  - Retrospectively gated phase-contrast (PC) magnetic resonance velocity and volume
      flow measurements were evaluated in both in vitro and in vivo experiments. The
      accuracy of these measurements was found to be affected by the interpolation
      window width required in the reconstruction of retrospectively gated data.
      Interpolation modified the frequency content of the series of temporal
      measurements by decreasing the response at higher frequencies. With a series of
      sinusoidal flow waveforms, the frequency response of one specific implementation
      of retrospectively gated PC velocity measurements was experimentally determined.
      The experimental response agreed with the theoretical response predicted from an
      analysis of the interpolating function (2.2% root-mean-square difference). In
      vitro experiments with a simulated carotid flow waveform demonstrated errors in
      the systolic measurements that were a direct result of the modified frequency
      response. A volunteer study was also undertaken and confirmed the in vitro
      findings.

PMID- 8280983
TI  - Diagnosis of bronchial rupture with MR imaging.
AB  - Tracheobronchial rupture is a serious injury occurring in approximately 1.5% of
      cases of major chest trauma. This injury is associated with significant mortality
      and morbidity and may be difficult to recognize both clinically and
      radiologically. Radiologic signs are mostly nonspecific, with pneumothorax and
      pneumomediastinum being the most common. A high level of suspicion is required to
      make the diagnosis. Computed tomography (CT) can be helpful; however, it provides
      only indirect evidence for the diagnosis. This report describes a case of
      complete transection of the right main bronchus, suspected at plain radiography
      and CT and clearly shown on magnetic resonance (MR) images. MR imaging, with its
      multiplanar capabilities, can be helpful in defining the location and extent of
      injury and in diagnosing injury not suspected or clearly demonstrated with other
      imaging modalities.

PMID- 8280984
TI  - MR imaging and proton spectroscopy of the brain in posttraumatic cortical
      blindness.
AB  - Magnetic resonance (MR) imaging and localized proton MR spectroscopy of the
      occipital lobes were performed in a patient with cortical blindness following
      brain trauma. Computed tomography (CT) scans and MR images of the visual cortex
      were normal in the acute stage. Six weeks after the trauma, MR images showed
      cortical lesions in both occipital lobes, while the spectra showed elevated
      lactate and decreased N-acetyl aspartate levels relative to those of healthy
      volunteers. One year later, visual acuity had improved and follow-up studies
      revealed an increase in the ratios of N-acetyl aspartate to choline and creatine.
      These results demonstrate that parenchymal lesions may develop in brain regions
      that appear normal at CT and MR imaging during the acute stage after trauma.
      Metabolic changes can be observed in these areas by means of localized proton MR
      spectroscopy.

PMID- 8280985
TI  - Applications of reduced-encoding MR imaging with generalized-series
      reconstruction (RIGR).
AB  - The RIGR (reduced-encoding imaging by generalized-series reconstruction)
      technique for magnetic resonance imaging uses a high-resolution reference image
      as the basis set for the reconstruction of subsequent images acquired with a
      reduced number of phase-encoding steps. The technique allows increased temporal
      resolution in applications requiring repeated acquisitions, such as the dynamic
      imaging of contrast agent biodistribution, and in intrinsically time-consuming
      protocols such as the acquisition of a series of T2-weighted images. Several
      examples are presented to demonstrate that a four- to eightfold improvement in
      spatial or temporal resolution can be achieved with this technique.

PMID- 8280986
TI  - Clinical MR desktop data.

PMID- 8280988
TI  - Acronyms.

PMID- 8280987
TI  - Physical MR desktop data.

PMID- 8280989
TI  - Glossary of MR terms. Third edition.

PMID- 8280990
TI  - SMRI MResource guide product listing and services directory. 1994 edition.

PMID- 8280991
TI  - Value of preoperative renal artery embolization in reducing blood transfusion
      requirements during nephrectomy for renal cell carcinoma.
AB  - PURPOSE: The authors evaluated the effectiveness of preoperative ethanol renal
      artery embolization in reducing transfusion requirements during nephrectomy for
      renal cell carcinoma. PATIENTS AND METHODS: Of 93 consecutive patients who
      underwent nephrectomy for renal cell carcinoma from 1980 to 1990, 24 patients
      underwent embolization within 24 hours of nephrectomy. Finding in this group were
      compared with those in 69 control patients who underwent surgery without
      preoperative embolization. RESULTS: Embolized tumors were larger than
      nonembolized ones (mean volume, 595 vs 257 mL) (P < .05). Patients with large
      hypervascular tumors (volume over 250 mL) who underwent complete embolization
      received significantly smaller mean blood transfusion volumes than control
      patients (250 vs 800 mL; P = .01). The transfusion volume associated with
      incomplete embolization was higher than that associated with no embolization.
      CONCLUSION: Complete alcohol embolization significantly reduces the volume of
      blood transfused during nephrectomy for large hypervascular renal cell
      carcinomas, and incomplete embolization is associated with larger transfusions.
      Preoperative embolization must be complete and should be performed more widely.

PMID- 8280992
TI  - Preoperative transcatheter embolization of abdominal pregnancy: report of three
      cases.

PMID- 8280993
TI  - Angiographic localization of small bowel angiodysplasia with use of platinum
      coils.

PMID- 8280994
TI  - In vivo and in vitro analysis of the effectiveness of doxorubicin combined with
      temporary arterial occlusion in liver tumors.
AB  - PURPOSE: The authors evaluated the effects of daunomycin (daunorubicin)--an
      analogue of doxorubicin--ethiodized oil, and arterial occlusion on an in vitro
      hepatoma analogue and on in vivo rat liver tumors. MATERIALS AND METHODS: A human
      Sk hepatoma cell monolayer sandwich system was used to determine uptake of 3H
      daunomycin under normoxic/hypoxic conditions with use of autoradiography.
      Fluorescence microscopy was used to evaluate the biodistribution of doxorubicin
      in cell cultures (human Sk hepatoma and colon carcinoma). Microvascular flow
      adjacent to and within liver tumors and the intrahepatic effects of doxorubicin
      and ethiodized oil were studied with in vivo video microscopy on exteriorized rat
      livers containing peripheral hepatomas. RESULTS: Increased uptake of 3H
      daunomycin by hepatoma cells occurred under hypoxic conditions. Intrahepatic
      arterial administration of ethiodized oil caused temporary occlusion of
      peripheral sinusoids following passage through arterioportal anastomoses. Tumors
      received portal venous and neovascular blood supply and ethiodized oil occluded
      but did not enter the narrow neovasculature perfusing the tumors. CONCLUSION:
      Hypoxia increases uptake of 3H-daunomycin by human Sk hepatoma and colon
      carcinoma cell cultures. Selective hepatic arterial occlusion (and perhaps the
      resultant hypoxia) may facilitate increased uptake of doxorubicin analogues into
      liver tumors. Hepatomas receive both arterial and portal venous blood supply, and
      ethiodized oil reaches the tumor via arterioportal anastomoses that perfuse the
      tumor periphery.

PMID- 8280995
TI  - Tantalum balloon-expandable stent: in vivo swine studies.
AB  - PURPOSE: The authors describe the experimental use of a balloon-expandable
      tantalum vascular stent in normal and atherosclerotic microswine. MATERIALS AND
      METHODS: Thirty-one stents (15 iliac, 13 aorta, two femoral, one renal) were
      placed in 11 animals. Stents were placed in both normal and stenotic
      atherosclerotic arteries. The animals were killed and the stents explanted 2-32
      weeks after placement. Arteriography was performed just prior to death in all
      cases. RESULTS: All stents were patent arteriographically and on gross
      inspection. Histopathologic study showed a thin, smooth, endothelial-lined
      neointima over the segments with stents. This covering had a mean thickness of
      2.9 x 10(-5) mm and appeared maximally developed 2-5 weeks after stent placement.
      The stent design incorporates the following engineering and clinical
      considerations: minimal profile and surface area and maximal expansion ratio,
      hoop strength, flexibility, fluoroscopic visibility, biocompatibility, and ease
      of placement. When compressed and mounted on the balloon catheter, the stent is
      flexible. This allows it to be easily maneuvered through tortuous or diseased
      vessels. On expansion, the stent becomes a semirigid tubular structure composed
      of multiple rhomboid cells. Stents with an expanded diameter of less than 11 mm
      can be introduced through a 7-F vascular sheath. CONCLUSION: Initial results
      suggest that this stent successfully incorporates a number of theoretically
      desirable features for a vascular prosthesis, and it may offer some advantages
      over previously described devices.

PMID- 8280996
TI  - Experimental study of balloon-expandable metallic vena caval stents in rabbits.
AB  - PURPOSE: The reactivity and patency of balloon-expandable Strecker stents were
      determined in the superior vena cava (SVC) and inferior vena cava (IVC) of
      rabbits. MATERIALS AND METHODS: One stent was placed in each of 24 rabbits; 15
      were placed in the SVC and nine in the IVC. The duration of stent placement
      varied between 3 days and 15 months. After the animals were killed, the segments
      in which the stent was placed were sectioned and analyzed under light microscopy
      for quantification of neointimal hyperplasia with metal struts in situ. RESULTS:
      Twenty-three stents remained patent throughout. Two SVC stents thrombosed at 1
      week; one of these recanalized spontaneously after 4 weeks. Self-limiting
      neointimal hyperplasia reached a maximum thickness at 1 month and receded over 3
      6 months. In five rabbits with long-term SVC stents, there was a radial shift of
      the stent to the perivascular layer of fat. Despite this shift, these stents
      remain patent. CONCLUSION: Strecker stents are well adapted to the venous system
      in terms of both patency and histocompatibility.

PMID- 8280997
TI  - Preliminary experimental evaluation of temporary segmental hepatic venous
      occlusion: angiographic, pathologic, and scintigraphic findings.
AB  - PURPOSE: Pigs were used to evaluate temporary segmental hepatic venous occlusion
      as a means of improving the selective delivery of therapeutic agents within the
      liver. MATERIALS AND METHODS: Hepatic angiography and scintigraphy were performed
      alone and in combination with hepatic venous occlusion. RESULTS: Arteriograms
      obtained during venous obstruction demonstrated a greater number of peripheral
      arterial branches in the occluded area compared with the nonoccluded areas. A
      prolonged hepatogram showing hepatofugal opacification of the portal branches was
      observed in the occluded area. Microscopically, mild congestion of the sinusoids
      and central veins was seen immediately after 60-minute occlusion, but these
      changes were not evident 2 hours after balloon deflation. Severe congestion and
      focal hemorrhage were found in the occluded segment of the liver 2 hours after 90
      minute venous occlusion. When the right or left hepatic vein was occluded during
      hepatic arterial infusion of technetium-99m macroaggregated albumin, there was a
      significant (P < or = .05) increase in the amount of radioactivity measured in
      the obstructed segment and a significant (P < or = .05) decrease in that found in
      the nonoccluded regions. CONCLUSION: These results indicate that temporary
      segmental hepatic vein occlusion is safe for up to 60 minutes and may be
      clinically applicable as a means of improving the therapeutic index of agents
      within the liver when they are administered via concomitant hepatic arterial
      infusion.

PMID- 8280998
TI  - Complications of percutaneously inserted biliary Wallstents.
AB  - PURPOSE: Complications were assessed during and after percutaneous Wallstent
      endoprosthesis insertion in patients with inoperable malignant biliary
      obstruction. PATIENTS AND METHODS: Two hundred seven Wallstents were inserted in
      176 patients: 74 had hilar strictures and 102 had distal strictures. Median
      survival after stent placement was 95 days. RESULTS: Early complications occurred
      in 12 patients (7%), predominantly cholangitis and reobstruction. Thirty-day
      mortality was 12%; 2% of deaths (three patients) were procedure related. Late
      complications, predominantly reobstruction, occurred in 35 patients (20%).
      Obstruction recurred in 33 patients (19%) after a median period of 135 days; 27
      had a hilar stricture. Tumor overgrowth was the major cause of reobstruction (n =
      19), especially proximal overgrowth. Tumor ingrowth caused reobstruction in three
      patients. Other causes were rare. No reobstruction due to sludge occurred.
      Reintervention was performed in 25 patients. Nineteen of the 25 patients
      benefited from repeated intervention. CONCLUSION: The use of the Wallstent is
      preferable to use of a plastic stent, as the major complication--reobstruction-
      is not stent related predominantly but is caused by tumor progression.

PMID- 8280999
TI  - Placement of covered self-expanding metallic stents in the common bile duct: a
      feasibility study.
AB  - PURPOSE: Gianturco self-expanding metallic stents have been useful in cases of
      benign biliary stenoses; however, the stents have not worked well in the presence
      of intraluminal tumor because of tumor growth between the wire struts. Stents
      were covered with polymeric membranes, which may prevent tumor ingrowth, and the
      feasibility of using these covered stents in the common bile duct was studied in
      healthy adult dogs. MATERIALS AND METHODS: Initially, stents (10 x 6 mm) covered
      with polycaprolactone (PCL), segmented polyether polyurethane (SPP), and silicone
      were placed in the common bile duct of dogs and were followed up for 3-12 months.
      Subsequently, four types of modified silicone-covered stents were evaluated.
      Rough-surface, small-diameter (3-mm), half-covered, and tapered stents were
      placed and followed up for 3 months. RESULTS: In the initial study, the SPP and
      silicone membranes remained intact, but the PCL covering broke in all dogs. In
      all but two dogs, luminal narrowing caused by varying degrees of papillary
      mucosal hyperplasia at both ends of the stent was observed. In the subsequent
      study, mucosal hyperplasia was considerably reduced by using half-covered stents
      and was virtually eliminated with tapered stents. All small-diameter stents
      migrated into the bowel. CONCLUSION: These studies suggest that tapered Gianturco
      self-expanding stents covered with silicone may be useful in the biliary tract in
      cases of intraluminal tumor.

PMID- 8281000
TI  - Histopathologic study of stenotic and occluded transjugular intrahepatic
      portosystemic shunts.
AB  - PURPOSE: A detailed histopathologic analysis of three stenotic and two occluded
      transjugular intrahepatic portosystemic shunts was performed to evaluate the
      nature and cause of each shunt abnormality. PATIENTS AND METHODS: The study group
      consists of five patients who developed a shunt stenosis or occlusion and
      subsequently underwent liver transplantation or autopsy. Shunt specimens were
      examined grossly and microscopically. RESULTS: The pseudointima was composed of
      granulation tissue, which was generally denser and more cellular near the luminal
      surface. Pseudointima was thicker in the parenchymal portion of the shunt than at
      the venous ends. A contiguous single layer of endothelial-like cells lined the
      majority of the luminal surface of each shunt. Scattered debris and clot covered
      10%-15% of the luminal surfaces. Transected bile ducts were noted in three cases.
      Bile staining was detected around the transected ducts, and bile pigment was
      incorporated into the developing pseudointima. CONCLUSIONS: Pseudointimal
      hyperplasia appears to be the causative lesion in these obstructions. An
      inflammatory reaction incited by bile extravasation may have contributed to
      pseudointimal proliferation in three cases.

PMID- 8281001
TI  - Stiffening cannula to facilitate tract dilation for transjugular intrahepatic
      portosystemic shunt placement.

PMID- 8281002
TI  - Treatment of portal vein thrombosis after liver transplantation with percutaneous
      thrombolysis and stent placement.

PMID- 8281003
TI  - Techniques for peripheral insertion of central venous catheters.

PMID- 8281004
TI  - Percutaneous retrieval of foreign bodies: experience with the nitinol Goose Neck
      snare.
AB  - PURPOSE: The authors present their experience with the nitinol Goose Neck snare
      system in the retrieval of retained foreign bodies in 20 patients. PATIENTS AND
      METHODS: Foreign bodies were located in the vascular system in 13 patients,
      urinary tract in four, biliary system in one, gastrointestinal tract in one, and
      the peritoneal space in one. All retrievals were performed with use of standard
      angiographic/interventional techniques. RESULTS: Success was achieved in all
      cases without attendant complications. Foreign bodies removed included catheter
      and guide-wire fragments, an embolization coil, broken or occluded double pigtail
      catheters, a Wallstent, and a surgical laparotomy sponge. CONCLUSION: All
      procedures were performed quickly, safely, and without difficulty. Because of its
      excellent torque control, positive grasping capacity, excellent radiopacity, lack
      of traumatic effect, and availability in different sizes appropriate for use in a
      wide variety of difficult anatomic spaces, the authors recommend that this device
      be considered the first choice for all foreign body retrieval procedures.

PMID- 8281005
TI  - Percutaneous retrieval of a large Palmaz stent from the pulmonary artery.

PMID- 8281006
TI  - Adventitial cystic disease of the popliteal artery mistaken for an endoluminal
      lesion.

PMID- 8281007
TI  - Biliary ductal shave biopsy with use of the Simpson atherectomy catheter.
AB  - PURPOSE: The authors performed percutaneous biliary ductal shave biopsy through
      an existing transhepatic biliary drainage tract with use of the Simpson
      atherectomy catheter. The technical feasibility, sensitivity, and complications
      of this endoluminal biopsy method were studied when used for diagnosis of biliary
      ductal and pancreatic neoplasm. PATIENTS AND METHODS: Nineteen bile duct shave
      biopsies were performed in 18 patients with symptomatic biliary obstruction by
      using a 9-F Simpson directional atherectomy catheter. Seven of the 18 patients
      underwent nine negative percutaneous needle biopsies prior to undergoing
      percutaneous biliary drainage. Results of previous transcatheter brush biopsies
      performed through the transhepatic tract were negative in all patients. RESULTS:
      A histologic diagnosis was obtained in 15 of the 19 procedures (sensitivity,
      0.79) and included cholangiocarcinoma (n = 7), pancreatic carcinoma (n = 5),
      metastatic carcinoma (n = 2), and primary sclerosing cholangitis (n = 1). Two
      complications occurred in the 19 procedures (10.5%), both transient but
      significant hemorrhage, one of which necessitated transfusion. CONCLUSIONS:
      Percutaneous biliary ductal shave biopsy with the Simpson atherectomy catheter
      can be performed successfully through the transhepatic approach and is a
      sensitive endoluminal biopsy technique, particularly in patients with tumors of
      the biliary tree that are not diagnosed by means of percutaneous needle biopsy or
      endoscopic methods. Disadvantages of this method include the high cost of the
      device and risk of hemorrhage. Atherectomy shave biopsy should be used cautiously
      and only after more conventional biopsy methods have been employed.

PMID- 8281008
TI  - Artificial extrapleural window for mediastinal biopsy.

PMID- 8281009
TI  - Splenic vein occlusion masquerading as portal hypertension with patent splenic
      vein.

PMID- 8281010
TI  - Safe landmarks for puncture of the femoral artery.

PMID- 8281011
TI  - Single-strand conformation polymorphism (SSCP) analysis as a tool for genetic
      mapping.

PMID- 8281012
TI  - Mapping the midkine family of developmentally regulated signaling molecules.
AB  - Midkine (Mdk) and heparin-binding neurotrophic factor (Hbnf)/pleiotrophin (Ptn)
      comprise the Midkine family of developmentally regulated signaling molecules. We
      have determined the chromosomal localization of these genes in the mouse by use
      of single-strand conformation polymorphisms (SSCPs), which facilitated the typing
      of Mdk and Hbnf alleles in recombinant inbred (RI) strains and interspecific
      backcrosses. Mapping was performed relative to other cloned genes, as well as
      simple sequence length polymorphisms (SSLPs) in the interspecific backcrosses.
      Mdk maps to mouse Chromosome (Chr) 2, linked to the Hoxd gene cluster. Hbnf maps
      to proximal mouse Chr 6, linked to the Cftr and Cpa genes. Comparative mapping of
      human MDK and HBNF employing species-specific polymerase chain reaction (PCR)
      primers and human monochromosomal somatic cell hybrids assigns MDK to human Chr
      11 and HBNF to human Chr 7q32-qter.

PMID- 8281013
TI  - Insertional mutation of the hairless locus on mouse chromosome 14.
AB  - Crosses between heterozygous transgenic mice from line 5053 produced offspring
      with progressive irreversible hair loss beginning at day 19. With increasing age,
      the skin of these animals became thicker and plicated in appearance. Histological
      analysis revealed the complete absence of normal hair follicles and numerous
      intradermic cystic structures, which enlarged with time and became filled with
      keratinaceous material. Test crosses demonstrated that the affected animals are
      homozygous for the transgene insertion. The clinical and histological phenotype
      of the new mutant closely resembles that of the rhino allele at the hairless
      locus on Chromosome (Chr) 14. Complementation tests and linkage analysis indicate
      that the transgene has interrupted the hairless locus. It has been demonstrated
      previously that mutation at the hr locus is accompanied by a variety of immune
      deficiencies. Many of the older affected transgenic mice developed an impetigo
      like skin eruption which responded to antibiotic ointment and which may reflect
      impaired immune function. The transgenic allele, hrTgN5053Mm, will be useful for
      identification of the transcription unit of the hairless locus.

PMID- 8281014
TI  - Linkage mapping of alpha-2 adrenergic receptor genes to mouse chromosomes 2 and
      5.
AB  - alpha-2 adrenergic receptors can be subdivided into three related subtypes which
      are conserved in humans, rats, and mice. In the mouse, these receptors are
      encoded by three genes (Adra-2a, Adra-2b, Adra-2c). To gain insight into the
      evolution of this multigene family and to investigate whether these genes are
      candidates for previously identified mouse mutations, we have determined the map
      positions of the Adra-2b and Adra-2c genes. The Adra-2a gene has been previously
      mapped to mouse Chromosome (Chr) 19 (Oakey et al. Genomics 10, 338-344, 1991).
      Using segregation among recombinant inbred strains of a single-stranded
      conformational polymorphism specific for alleles of Adra-2b and Adra-2c, we
      present map positions for these genes on mouse Chrs 2 and 5, respectively. In the
      case of Adra-2b, these results have been confirmed by an analysis of somatic cell
      hybrids. In addition, we generate AKXD recombinant inbred strain distribution
      patterns for 11 previously defined SSLP microsatellite markers, further refining
      the haplotype maps for these chromosomes. Finally, several candidate mouse
      mutations that map close to Adra-2b and Adra-2c are discussed.

PMID- 8281015
TI  - Chromosomal localization of uroplakin genes of cattle and mice.
AB  - The asymmetric unit membrane (AUM) of the apical surface of mammalian urinary
      bladder epithelium contains several major integral membrane proteins, including
      uroplakins IA and IB (both 27 kDa), II (15 kDa), and III (47 kDa). These proteins
      are synthesized only in terminally differentiated bladder epithelial cells. They
      are encoded by separate genes and, except for uroplakins IA and IB, appear to be
      unrelated in their amino acid sequences. The genes encoding these uroplakins were
      mapped to chromosomes of cattle through their segregation in a panel of bovine x
      rodent somatic cell hybrids. Genes for uroplakins IA, IB, and II were mapped to
      bovine (BTA) Chromosomes (Chrs) 18 (UPK1A), 1 (UPK1B), and 15 (UPK2),
      respectively. Two bovine genomic DNA sequences reactive with a uroplakin III cDNA
      probe were identified and mapped to BTA 6 (UPK3A) and 5 (UPK3B). We have also
      mapped genes for uroplakins IA and II in mice, to the proximal regions of mouse
      Chr 7 (Upk1a) and 9 (Upk2), respectively, by analyzing the inheritance of
      restriction fragment length variants in recombinant inbred mouse strains. These
      assignments are consistent with linkage relationships known to be conserved
      between cattle and mice. The mouse genes for uroplakins IB and III were not
      mapped because the mouse genomic DNA fragments reactive with each probe were
      invariant among the inbred strains tested. Although the stoichiometry of AUM
      proteins is nearly constant, the fact that the uroplakin genes are unlinked
      indicates that their expression must be independently regulated. Our results also
      suggest likely positions for two human uroplakin genes and should facilitate
      further analysis of their possible involvement in disease.

PMID- 8281016
TI  - A physical map of the human APP gene in YACs.
AB  - Several point mutations within exons 16 and 17 of the amyloid precursor protein
      (APP) gene have been reported that are associated with Alzheimer's disease in a
      small number of familial cases. To determine the size of the APP gene and the
      organization of the exons within human genomic DNA, we have characterized 11
      Yeast Artificial Chromosome (YAC) recombinants containing human APP gene
      sequences. The smallest YAC insert was 125 kb, and the largest was 1.4 Mb. The
      YACs were screened by polymerase chain reaction amplification of APP exons to
      determine which of the 18 exons coding for APP770 were present. Four of the YACs
      (D110G1, D110G6, D110E9, and B142F9) contain all 18 exons and at least part of
      the promoter. Construction of an overlapping map of the gene with all of the YACs
      demonstrated that 3 of the 11 YACs were chimeric. The orientation and position of
      the coding sequence on the map was determined by probing digests of the YAC DNA
      with exon PCR products and the vector arms. The coding region of the APP gene
      spans approximately 400 kb of genomic DNA.

PMID- 8281017
TI  - Mapping of new bovine microsatellites on cattle chromosome 15 with somatic cell
      hybrids, linkage analysis, and fluorescence in situ hybridization.

PMID- 8281018
TI  - Sequence analysis of a deleted mitochondrial DNA molecule in heteroplasmic mice.

PMID- 8281019
TI  - Localization of the twitcher (twi) mutation on mouse chromosome 12.

PMID- 8281020
TI  - A response to the British Paediatric Association report on paediatric intensive
      care services.

PMID- 8281021
TI  - Role of the health services in the aftermath of the Bulger case.

PMID- 8281022
TI  - Nursing care of the patient with altered body image.
AB  - Body image is influenced by our environment and the people around us. Alteration
      in normal body image has many components, i.e. biological, psychological and
      social. These must all be taken into account when nursing the patient with an
      altered body image as they have great implications for care.

PMID- 8281023
TI  - Suicidal behaviour.
AB  - This article challenges the traditional viewpoint of attempted suicide as a
      generic term. It argues that greater use could be made, by both medical and
      nursing staff, of the terms parasuicide and attempted suicide, and that
      therapeutic intervention could be improved if both terms are considered when
      making a diagnosis.

PMID- 8281024
TI  - Design of primary nursing jobs in a paediatric unit.
AB  - Nursing jobs in the four wards of a paediatric unit were evaluated in a job
      diagnostic survey before the introduction of a primary nursing regimen. The
      approach used was a combination of task and patient allocation on a shift basis.

PMID- 8281026
TI  - Changing influence of occupational sociology.

PMID- 8281025
TI  - A study of microorganism levels on nurses' footwear.
AB  - This study looks at the microbial colonies that are present on nurses' shoes, and
      the growth patterns of these colonies over the span of a working shift.

PMID- 8281027
TI  - Can performance-related pay be adapted for nursing?

PMID- 8281028
TI  - Spina bifida: the personal and financial cost of incontinence.
AB  - Spina bifida is a congenital defect in the spinal column in which one or more
      vertebrae fail to form. The effect of spina bifida on continence is usually
      complicated by the effect of hydrocephalus on the ability to learn and master the
      necessary skills to overcome the problems. The childhood and adolescence of some
      individuals who have spina bifida has been ruined by professionals who chose to
      ignore the wider implications of severe congenital disability and its effects
      upon the child's education, personal and social development, and the quality of
      family life. A holistic approach to management, from birth onwards, should
      facilitate the interdisciplinary cooperation which is vital if these human
      tragedies are to be avoided.

PMID- 8281029
TI  - Nurse-aid management of psychological emergencies: 3.
AB  - Anxiety can endanger life and hinder recovery. Early intervention reduces anxiety
      and therefore limits the risks. This article describes the recognition of anxiety
      and outlines some nursing interventions. Although it concentrates on the
      hospitalized patient the methods can be used in a variety of situations,
      particularly first-aid situations where anxiety can add to the severity of the
      situation.

PMID- 8281030
TI  - Accountancy made simple.
AB  - A well-run accounts department is a boon to any organization. What are its
      functions within the NHS and how does it affect the daily lives of NHS
      professionals?

PMID- 8281032
TI  - Expression of the alpha beta T-cell receptor is necessary for the generation of
      the thymic medulla.
AB  - The architecture of the thymus of mice that congenitally fail to express the
      alpha beta T-cell receptor (TCR alpha beta) has been examined by immunohistology.
      In these mice, a defined mutation was introduced into the TCR alpha gene by
      homologous recombination. By using antibodies specific for cortical or medullary
      epithelium and for major histocompatibility complex antigens, the network of
      cortical epithelium in these mice was shown to be essentially unaltered in
      comparison with that of normal mice. In contrast, the thymic medulla was
      considerably reduced in size. This analysis shows that expression of the alpha
      beta TCR but not the gamma delta TCR is obligatory for establishing the thymic
      medulla and suggests that the growth of medullary epithelial cells may require
      contact with TCR alpha beta-expressing cells.

PMID- 8281031
TI  - Positive and negative selection in transgenic mice expressing a T-cell receptor
      specific for influenza nucleoprotein and endogenous superantigen.
AB  - A transgenic mouse was generated expressing on most (> 80%) of thymocytes and
      peripheral T cells a T-cell receptor isolated from a cytotoxic T-cell clone (F5).
      This clone is CD8+ and recognizes alpha alpha 366-374 of the nucleoprotein (NP
      366-374) of influenza virus (A/NT/60/68), in the context of Class I MHC Db
      (Townsend et al., 1986). The receptor utilizes the V beta 11 and V alpha 4 gene
      segments for the beta chain and alpha chain, respectively (Palmer et al., 1989).
      The usage of V beta 11 makes this TcR reactive to Class II IE molecules and an
      endogenous ligand recently identified as a product of the endogenous mammary
      tumour viruses (Mtv) 8, 9, and 11 (Dyson et al., 1991). Here we report the
      development of F5 transgenic T cells and their function in mice of the
      appropriate MHC (C57BL/10 H-2b, IE-) or in mice expressing Class II MHC IE (e.g.,
      CBA/Ca H-2k and BALB/c H-2d) and the endogenous Mtv ligands. Positive selection
      of CD8+ T cells expressing the V beta 11 is seen in C57BL/10 transgenic mice (H
      2b). Peripheral T cells from these mice are capable of killing target cells in an
      antigen-dependent manner after a period of in vitro culture with IL-2. In the
      presence of Class II MHC IE molecules and the endogenous Mtv ligand, most of the
      single-positive cells carrying the transgenic T-cell receptor are absent in the
      thymus. Unexpectedly, CD8+ peripheral T-cells in these (H-2k or H-2d) F5 mice are
      predominantly V beta 11 positive and also have the capacity to kill targets in an
      antigen-dependent manner. This is true even following backcrossing of the F5 TcR
      transgene to H-2d scid/scid mice, in which functional rearrangement of endogenous
      TcR alpha- and beta-chain genes is impaired.

PMID- 8281033
TI  - A selective culture system for generating terminal deoxynucleotidyl transferase
      positive lymphoid cells in vitro. V. Detection of stage-specific pro-B-cell
      stimulating activity in medium conditioned by mouse bone marrow stromal cells.
AB  - The selective in vitro generation of rat, mouse, and human terminal
      deoxynucleotidyl transferase-positive (TdT+) lymphoid cells in our long-term
      xenogeneic bone marrow (BM) culture system is characterized by physical
      interaction between the developing lymphocytes and mouse BM-adherent stromal
      cells and macrophages. In the present study, experiments in which microporous
      membrane culture inserts were inoculated with rat BM cells demonstrated that
      although the generation of primitive B-lineage lymphoid cells requires the
      presence of a mouse BM feeder layer, cognitive recognition events are not
      necessary. Similarly, cell-free (and serum-free) medium conditioned with mouse BM
      (but not thymus or spleen) adherent cells and stromal-cell lines therefrom
      supported the proliferation of early rat lymphoid cells in a dose-dependent
      manner. Double immunofluorescence for incorporated bromo-deoxyuridine (BrdU) and
      early B-lineage markers of rat BM lymphoid cells maintained in culture inserts or
      conditioned medium (CM), and studies of their in vitro and in vivo developmental
      potentials, indicated that the lymphoproliferative response resulted from the
      selective stimulation of lymphoid stem and/or progenitor cells. The most
      primitive of these target cells had a HIS24+ HIS50- TdT- c mu- sIg-, pre-pro-B
      cell phenotype. Whereas this subset normally constitutes less than 2% of B
      lineage BM cells in vivo, it comprises more than 25% of total lymphoid cells in
      vitro. In addition, the number of TdT+ cells, predominantly of the early pro-B
      cell phenotype (HIS24+ HIS50- c mu- sIg-), was increased approximately tenfold
      above input levels. Based on these and previous findings, a schematic model is
      proposed for the developmental pathway of early B-lineage cells in rat BM from
      the level of the committed (possibly common) lymphoid stem cell to that of the
      pre-B-cell.

PMID- 8281034
TI  - IgH diversity in an individual with only one million B lymphocytes.
AB  - Immunoglobulin sequences from an individual Xenopus laevis froglet were analyzed
      for combinatorial and junctional diversity. In an animal with about 10(6) B
      lymphocytes, at least 26 out of the 56 VH1 genes available in a diploid genome
      were expressed, as were all JH segments. Junctional diversity was similar to that
      observed in Xenopus tadpole sequences, that is, little or no N diversification
      was found and the recombination site sometimes occurred in a region of V/D or D/J
      homology. The froglet IgH diversity is further restricted by the elimination of D
      gene participation through direct V to J joining. Of the six complementary
      determining regions (CDR) contributing to the structure of the antigen-combining
      site, CDR3 is the most variable in sequence and structure. Froglet IgH CDR3 are
      restricted to both aspects. Compared to IgH sequences isolated from a 5-month-old
      adult, froglet CDR3 were, on the average, two codons shorter; overall, 58% of the
      froglet Ig sequences isolated carried CDR3 of < or = 7 codons, compared to 30% of
      the adult sequences. In addition to being shorter, the tadpole/froglet CDR3 are
      less variable in sequence, as the absence of N regions also results in the V/D
      and D/J junctions being derived from germline elements. We therefore suggest that
      latent anti-adult specificities are not eliminated in situ, in the tadpole, but
      rather that such germline gene segments, singly or in their combinations thereof,
      that can potentially react to adult self-epitopes after metamorphosis have been
      counterselected during the course of evolution.

PMID- 8281035
TI  - Transforming growth factor beta (TGF beta) is produced by and influences the
      proliferative response of Xenopus laevis lymphocytes.
AB  - Both TGF beta 2 and 5 have been described in the South African clawed frog
      Xenopus laevis and have been cloned from the tadpole-derived fibroblast cell
      line, XTC. Because TGF beta has such a profound inhibitory effect on the
      mammalian immune system, this study was performed to determine whether TGF beta:
      (a) has any in vitro effects on the growth of Xenopus lymphoblasts, and (b) is
      produced by mitogen-activated Xenopus lymphocytes. Following stimulation with
      mitogen or alloantigen, T lymphocytes from Xenopus secrete a T-cell growth factor
      (TCGF) that is functionally homologous to mammalian interleukin-2 (IL-2). Both
      recombinant human TGF beta 1 and Xenopus TGF beta 5 inhibit TCGF-induced
      proliferation of Xenopus splenic blasts and this inhibition can be reversed with
      anti-pan TGF beta antiserum. The Xenopus mitogen-induced saturated ammonium
      sulfate precipitated TCGF-containing supernatant (SAS TCGF SN) also contains
      latent TGF beta as assayed on mink lung fibroblasts and Xenopus splenic blasts,
      and experiments utilizing anti-TGF beta antiserum showed that only TGF beta 5 is
      present in this supernatant.

PMID- 8281036
TI  - Further characterization of an interleukin-2-like cytokine produced by Xenopus
      laevis T lymphocytes.
AB  - A T-cell growth factor (TCGF) is produced by antigen- or mitogen-stimulated T
      lymphocytes from the South African clawed frog Xenopus laevis. This study further
      defines the physical and biological properties of this cytokine and demonstrates
      that TCGF is biochemically similar to mammalian interleukin-2 (IL-2).
      Biologically active TCGF eluted from SDS-PAGE displays a M(r) of 16 kD and lectin
      affinity chromatography indicates that the three-dimensional configuration of
      carbohydrates on TCGF and human IL-2 is similar. Secretion of TCGF is detectable
      1 day after stimulation of splenocytes with the T-cell mitogen phytohemagglutinin
      (PHA) and peaks following 2 to 3 days of stimulation. Finally, despite the
      biological and physical similarities between Xenopus TCGF and mammalian IL-2,
      anti-human IL-2 monoclonal antibodies do not recognize Xenopus TCGF.

PMID- 8281037
TI  - Regulation of Arabidopsis flower development.

PMID- 8281038
TI  - Anther development: basic principles and practical applications.

PMID- 8281039
TI  - Sex determination in flowering plants.
AB  - In many ways, plants offer unique systems through which to study sex
      determination. Because the production of unisexual flowers has evolved
      independently in many plant species, different and novel mechanisms may be
      operational. Hence, there is probably not one unifying mechanism that explains
      sex determination in plants. Advances in our understanding of sex determination
      will come from the analysis of the genetics, molecular biology, and biochemistry
      of genes controlling sexual determination in plants. Several excellent model
      systems for bisexual floral development (Arabidopsis and Antirrhinum), monoecy
      (maize), and dioecy (Silene, asparagus, and mercury) are available for such
      analyses. The important questions that remain concern the mechanism of action of
      sex determination genes and their interrelationship, if any, with homeotic genes
      that determine the sexual identity of floral organ primordia. At the
      physiological level, the connection between hormone signaling and sexuality is
      not well understood, although significant correlations have been discovered.
      Finally, once the genes that regulate these processes are identified, cloned, and
      studied, new strategies for the manipulation of sexuality in plants should be
      forthcoming.

PMID- 8281040
TI  - Endosperm origin, development, and function.

PMID- 8281041
TI  - Gene expression during plant embryogenesis and germination: an overview.

PMID- 8281044
TI  - Health care reform. New directions in health care.

PMID- 8281042
TI  - Sexual pheromones and mating responses in fungi.

PMID- 8281045
TI  - Health care reform. Saskatchewan vision for health.

PMID- 8281046
TI  - Health care reform. An invitational conference: enhancing prevention in the
      practice of health professionals. Interview by J Johnson.

PMID- 8281047
TI  - Health care reform. First responders in Saskatchewan.

PMID- 8281048
TI  - How "malignant" is the neuroleptic malignant syndrome?

PMID- 8281049
TI  - Human T cell leukaemia/lymphoma virus and blood donation.

PMID- 8281050
TI  - Identifying hearing impairment in infants and young children.

PMID- 8281051
TI  - p53: a gene for all tumours?

PMID- 8281052
TI  - Information management and patient privacy in the NHS.

PMID- 8281053
TI  - German AIDS scandal infects Europe.

PMID- 8281054
TI  - Prevalence of antibodies to human T cell leukaemia/lymphoma virus in blood donors
      in north London.
AB  - OBJECTIVES: To determine the prevalence of antibodies to the human T cell
      leukaemia/lymphoma viruses (HTLV-I and HTLV-II) in blood donors in north London
      in order to assess the economic impact and the logistic effects that routine
      screening would have on the blood supply. DESIGN: All donations collected by the
      north London blood transfusion centre between January 1991 and June 1991 were
      screened for antibodies to HTLV-I and HTLV-II by modified, improved Fujirebio gel
      particle agglutination test. Positive samples were titrated and retested as
      necessary. SUBJECTS: 96,720 unpaid volunteers, who gave 105,730 consecutive
      donations of blood and plasma. SETTING: North London blood transfusion centre.
      MAIN OUTCOME MEASURE: Observed numbers of donors confirmed to be seropositive for
      HTLV by reference laboratories. RESULTS: Of 2622 (2.5%) initially reactive
      samples, 414 (0.4% of all samples) gave a titre of > or = 1 in 16 on the modified
      agglutination test. Thirty five of the 414 serum samples yielded positive results
      on one of two enzyme linked immunosorbent assays (ELISA (Cambridge Biotech and
      Abbot)), and none of these results were confirmed by either reference laboratory.
      Five samples yielded positive results on both ELISAs and all five of these were
      confirmed to contain antibodies to HTLV. One of the five contained antibodies to
      HTLV-II and the others antibodies to HTLV-I. Four seropositive donors were white
      women whose only risk factor for infection was sexual contact. The fifth
      (positive for antibodies to HTLV-II) was an Anglo-Caribbean man who admitted to
      previous misuse of intravenous drugs. CONCLUSION: The prevalence of antibodies to
      HTLV in blood donors in north London was one in 19,344 (0.005%). Up to 100 donors
      a year might be identified in the United Kingdom as being infected with HTLV,
      although prevalence in different regions may vary considerably.

PMID- 8281055
TI  - Twins, triplets, and cerebral palsy in births in Western Australia in the 1980s.
AB  - OBJECTIVES: To examine the rate of cerebral palsy in twins and triplets in births
      from 1980 to 1989 in Western Australia and to identify factors associated with
      increase in risk. DESIGN: Pluralities for all births in Western Australia were
      identified through the standardised midwives' notification system, and cases of
      cerebral palsy were identified from the Western Australian cerebral palsy
      register. MAIN OUTCOME MEASURES: Multiple births, cerebral palsy, excluding
      postneonatal cause. RESULTS: The prevalence of cerebral palsy in triplets, of 28
      per 1000 survivors to 1 year (95% confidence interval 11 to 63) exceeded that in
      twins (7.3; 5.2 to 10) and singletons (1.6; 1.4 to 1.8). Although twins and
      triples were more likely than singletons to be low in birth weight, their risks
      of cerebral palsy if low in birth weight were similar. In contrast, in normal
      birthweight categories twins had a higher rate of cerebral palsy (4.2; 2.2 to
      7.7) than singletons (1.1; 1.0 to 1.3). The prevalence of cerebral palsy was
      similar in twins of unlike sex pairs, all of whom are dizygotic, and in like sex
      pairs. A twin pair in which one member died in utero was at higher risk of
      cerebral palsy: 96 per 1000 twin pairs (36 to 218) compared with 12 (8.2 to 17)
      for twin pregnancies in which both survived. There was a similar but non
      significant trend for death of one triplet to be associated with increased risk
      of cerebral palsy in the survivors of the set. CONCLUSION: Triplet pregnancies
      produced a child with cerebral palsy 47 times more often than singleton
      pregnancies did and twin pregnancies eight times more often. Eighty six per cent
      of cerebral palsy in multiple births was in twins. As multiple births are
      increasing mainly because of personal and medical decisions the increased risk of
      cerebral palsy in multiple births is of concern.

PMID- 8281056
TI  - Early programmes of high and low intensity exercise and quality of life after
      acute myocardial infarction.
AB  - OBJECTIVE: To determine whether a group programme of light exercise could improve
      quality of life in patients after acute myocardial infarction to the same extent
      as a high intensity exercise training programme. SETTING: Australian teaching
      hospital. PATIENTS: 224 men from a consecutive series of 339 men under 70
      admitted to a coronary care unit with transmural acute myocardial infarction.
      INTERVENTION: Patients were randomly allocated in hospital to a group programme
      lasting eight weeks of either high intensity exercise training or light exercise.
      MAIN OUTCOME MEASURES: Physical working capacity based on metabolic equivalents
      achieved from treadmill exercise tests at entry, after 11 weeks, and after one
      year. Quality of life based on self report scores of anxiety, depression, denial,
      and wellbeing and interview assessments of activities and psychosocial adjustment
      at entry, after four months, and after one year. RESULTS: The two groups were
      well matched at entry. At 11 weeks the mean results of treadmill testing were
      10.7 (95% confidence interval 10.20 to 11.20) metabolic equivalents for exercise
      training and 9.7 (9.26 to 10.14) for light exercise (t = 2.85, df = 181, p =
      0.005). Apart from this small temporary benefit in mean physical working
      capacity, there were no significant differences between groups. Improvement in
      occupational adjustment score from baseline to four months was greater after
      exercise training than after light exercise, but at one year repeated measures
      analysis of variance showed no significant effects of treatment or interaction
      between treatment and time point. CONCLUSION: The effects on quality of life of a
      low cost programme of light exercise are similar to those obtained from a high
      intensity exercise training programme.

PMID- 8281057
TI  - Initial effects of the grounding of the tanker Braer on health in Shetland. The
      Shetland Health Study Group.
AB  - OBJECTIVE: To determine if the oil spillage from the tanker Braer had any
      immediate health effects on the exposed resident population. DESIGN: Cohort study
      with a comparison against controls, exposure status being assigned on the basis
      of geographical location. SETTING: Rural Shetland. SUBJECTS: All those resident
      on or after 5 January 1993 (day 0) within 4.5 km of the site of tanker's
      grounding. Controls matched for sex and age were drawn from a general practice
      list 95 km distant. OUTCOME MEASURES: Demographic details; smoking and alcohol
      consumption; perception of health and reported presence or absence of specific
      symptoms; peak expiratory flow; results of haematology, liver and renal function
      tests, and blood and urine toxicology. RESULTS: Of subjects contacted, 420 (66%)
      exposed people and 92 (68%) controls were studied; 56 non-attenders were
      surveyed. Principal health effects arose on days 1 and 2 and were headache,
      throat irritation, and itchy eyes. No significant differences between those
      exposed and controls were found for any of the biological markers. Toxicological
      studies did not show any exposures that are known to affect human health.
      CONCLUSIONS: The study confirmed the anecdotal reports of certain acute symptoms.
      No evidence of pulmonary, haematological, renal, or hepatic damage was detected
      at the population level. Toxicological samples from exposed people did not find
      levels known to affect human health. Further studies are required to ascertain
      whether there have been any long term effects on the population.

PMID- 8281058
TI  - Acute myocardial infarction in patients with normal coronary arteries.

PMID- 8281059
TI  - Public opinion on different approaches to teaching intubation techniques.

PMID- 8281060
TI  - Commodes: inconvenient conveniences.
AB  - OBJECTIVES: To investigate use of commodes and attitudes of users and carers to
      them. DESIGN: Interview with semi-structured questionnaire of subjects supplied
      with commodes from Leeds community appliance centre. SUBJECTS: 140 users of a
      commode and 105 of their carers. RESULTS: Main reasons for being supplied with a
      commode were impaired mobility (130 subjects), difficulty in climbing stairs
      (128), and urinary incontinence (127). Main concerns of users and carers were
      lack of privacy (120 subjects felt embarrassed about using their commode, and 96
      would not use it if someone was present); unpleasant smells (especially for 20
      subjects who were confined to one room); physical appearance of commode chair
      (101 users said it had an unfavourable appearance, and 44 had tried to disguise
      it); and lack of follow up after commode was supplied (only 15 users and carers
      knew who to contact if there were problems). Users generally either had very
      positive or very negative attitudes to their commodes but most carers viewed them
      very negatively, especially with regard to cleaning them. CONCLUSIONS: Health
      professionals should be aware of people's need for privacy when advising them
      where to keep their commode. A standard commode is inappropriate for people
      confined to one room, and alternatives such as a chemical toilet should be
      considered. Regular follow up is needed to identify any problems such as
      uncomfortable or unsafe chairs. More thought should be given to the appearance of
      commodes in their design.

PMID- 8281061
TI  - How to achieve better outcome in treatment of asthma in general practice.
AB  - The symptoms of many asthmatic patients are poorly controlled, and there are
      several reasons why this may be so. Doctors fail to find out about symptoms that
      asthmatic patients are experiencing. Doctors wrongly assume that regular use of
      bronchodilators in small doses is satisfactory treatment for asthma and that
      taking high doses of bronchodilator in an asthma attack may be dangerous. Doctors
      think that inhaled steroids may be dangerous and are reluctant to use them in
      effective doses. Doctors do not check that patients can use their inhalers
      properly and do not make enough use of large volume spacers, the best available
      method for giving inhaled asthma treatment. Doctors undermine patients'
      confidence in advice on treatment by failing to ensure that consistent advice is
      given and often make the management of asthma more troublesome for the patient
      than the symptoms of asthma.

PMID- 8281062
TI  - Design a questionnaire.
AB  - The design of questionnaires is a craft which has been badly neglected by the
      medical profession. A questionnaire should be appropriate, intelligible,
      unambiguous, unbiased, capable of coping with all possible responses,
      satisfactorily coded, piloted, and ethical. The key steps in designing a
      questionnaire are to: decide what data you need, select items for inclusion,
      design the individual questions, compose the wording, design the layout and
      presentation, think about coding, prepare the first draft and pretest, pilot, and
      evaluate the form, and perform the survey. Despite the apparently complicated
      nature of the task, theoretical knowledge is no substitute for practical
      experience.

PMID- 8281063
TI  - General surgery: biliary surgery.
AB  - The management of biliary tract disease has changed completely as a result of
      minimally invasive treatment. For most patients with gallstones that cause
      symptoms a laparoscopic cholecystectomy will treat the condition with minimal
      morbidity and a short recovery period. If complications are encountered,
      conversion to a mini-cholecystectomy gives results that are nearly as good. Acute
      cholecystitis can be treated by percutaneous drainage followed either by
      percutaneous cholecystolithotomy or a laparoscopic cholecystectomy. Gallstones in
      the bile duct are best treated by endoscopic sphincterotomy with duct clearance.
      The day of the large cholecystectomy scar with its subsequent incisional hernia
      has gone.

PMID- 8281064
TI  - Making the internal market work: a case for managed change.
AB  - The internal market in the NHS is meant to ensure that provider units compete on
      the basis of price and quality and that money follows patients into efficient
      units. But the example of what happened to one local ophthalmology unit suggests
      what may go wrong when entrepreneurial activity is applied in a market that does
      not work perfectly. In 1991-2 the unit had a high workload but also comparatively
      high prices (because of crude pricing in the local hospital); because of pressure
      of work the waiting times lengthened and general practitioners increasingly
      complained about the service. The staff in the unit reopened a longstanding
      debate about the need for a third consultant ophthalmologist, but neither the
      purchasers (including fundholders) nor the provider unit were able to fund the
      post. Fundholders in a neighbouring district, however, together with that
      district health authority, decided to place their contracts elsewhere for the
      following year. Although the withdrawal of contracts jeopardised the clinical and
      financial viability of the ophthalmic unit, patients continued to use the
      service. When general practitioners in the district realised that their local
      service might collapse they pressed to keep the service open. The fundholders and
      the host purchaser finally agreed to fund a third consultant and drew up
      standards for the service. As a result the waiting times fell and the service is
      now described as "excellent." Short term market decisions may have unforseen long
      term implications for services to patients. This needs to be addressed as part of
      the evolution of the reformed NHS.

PMID- 8281065
TI  - Gastric cancer. Abandon quick gastrectomies.

PMID- 8281066
TI  - Gastric cancer. Push for prompt endoscopy.

PMID- 8281067
TI  - Gastric cancer. No proof that early diagnosis reduces mortality.

PMID- 8281068
TI  - Screening for breast cancer. Has no impact on mortality.

PMID- 8281069
TI  - Screening for breast cancer. Mammography unsafe and unreliable.

PMID- 8281070
TI  - Hormone treatment for infertility. Restrictions won't prevent multiple
      pregnancies.

PMID- 8281071
TI  - Hormone treatment for infertility. A chance for those who can't pay for IVF.

PMID- 8281072
TI  - Psychiatric consequences of road traffic accidents. Consider somatoform pain
      disorder.

PMID- 8281073
TI  - Thyroid function in elderly people.

PMID- 8281074
TI  - Psychiatric consequences of road traffic accidents. Children may be seriously
      affected.

PMID- 8281075
TI  - Psychiatric consequences of road traffic accidents. Often disabling and
      unrecognised.

PMID- 8281076
TI  - Psychiatric consequences of road traffic accidents. Phobias linked to chronic
      pain.

PMID- 8281077
TI  - Women in medicine. Need flexible training.

PMID- 8281078
TI  - Women in medicine. Hidden processes hold women back.

PMID- 8281079
TI  - Women in medicine. Interview panels still prejudiced.

PMID- 8281080
TI  - Efficient purchasing.

PMID- 8281081
TI  - Could hospitals do more to encourage breast feeding?

PMID- 8281082
TI  - Medical accidents: no such thing?

PMID- 8281083
TI  - Explaining referral variation.

PMID- 8281084
TI  - Junior doctors' hours: the way forward.

PMID- 8281085
TI  - Screening for HIV-1 antibodies in pregnancy: results from the Swedish national
      programme.
AB  - OBJECTIVE: To determine the effectiveness of a national screening programme for
      HIV infection in pregnant women. DESIGN: Observational study. SUBJECTS: All
      pregnant women presenting to antenatal or abortion clinics. SETTING: Sweden,
      September 1987 to December 1991. MAIN OUTCOME MEASURES: Number and
      characteristics of infected women. RESULTS: By the end of the study period
      510,000 tests had been performed and 54 women with HIV infection identified
      (1.06/10,000). Of the 33 women identified in Stockholm, 14 women (4.4/10,000) had
      attended abortion clinics and 19 antenatal clinics (1.8/10,000; p < 0.05). Three
      women had been intravenous drug users, one was infected through a blood
      transfusion, and 50 were probably infected sexually. Of the 20 women who attended
      antenatal clinics early enough to allow an abortion, 12 continued with their
      pregnancies. CONCLUSIONS: Testing of all women, not just those perceived to be at
      risk, probably contributed to the high uptake of HIV testing. With high uptake
      such screening provides valuable data on spread of HIV in the heterosexual
      population and presents opportunity for preventing transmission of HIV to
      children and partners.

PMID- 8281086
TI  - Relation between birth weight and blood pressure: longitudinal study of infants
      and children.
AB  - OBJECTIVE: To study the relation between birth weight and systolic blood pressure
      in infancy and early childhood. DESIGN: Longitudinal study of infants from birth
      to 4 years of age. SETTING: A middle class community in the Netherlands.
      PARTICIPANTS: 476 Dutch infants born in 1980 to healthy women after uncomplicated
      pregnancies. MAIN OUTCOME MEASURES: Systolic blood pressure and body weight
      measured at birth and at 3 months and 4 years of age; the relation between
      systolic blood pressure and birth weight as estimated by multiple regression
      models that include current weight and previous blood pressure and control for
      gestational age, length at birth, and sex. RESULTS: Complete data were available
      on 392 infants. At 4 years of age the relation between blood pressure and birth
      weight appeared to be U shaped; low and high birthweight infants had raised blood
      pressure. Current weight and previous blood pressure were also positively
      associated with blood pressure at that age. Low birthweight infants (birth weight
      < 3100 g) had a greater gain in blood pressure and weight in early infancy. High
      birthweight infants (birth weight > or = 3700 g) had high blood pressure at
      birth, and weight and blood pressure tended to remain high thereafter.
      CONCLUSIONS: Even among normal infants there seem to be subgroups defined by
      birth weight in which blood pressure is regulated differently. Future
      investigations are needed to examine the physiological basis of these
      differences. Studies of correlates of adult disease related to birth weight
      should investigate mechanisms related to increased risk separately in infants of
      low and high birth weight.

PMID- 8281087
TI  - Deprivation, low birth weight, and children's height: a comparison between rural
      and urban areas.
AB  - OBJECTIVE: To compare proportions of low birthweight babies and mean heights of
      schoolchildren between rural and urban areas at different levels of social
      deprivation. DESIGN: Cross sectional population based study classifying cases by
      Townsend material deprivation index of enumeration district of residence and by
      rural areas, small towns, and large towns. SETTING: Northumberland Health
      District. SUBJECTS: 18,930 singleton infants delivered alive during January 1985
      to September 1990 and resident in Northumberland in October 1990; 9055 children
      aged 5 to 8 1/2 years attending Northumberland schools in the winter of 1989-90.
      MAIN OUTCOME MEASURES: Odds ratios for birth weight less than 2800 g; difference
      in mean height measured by standard deviation (SD) score. RESULTS: Between the
      most deprived and most affluent 20% of enumeration districts the odds ratio for
      low birth weight adjusted for rural or urban setting was 1.71 (95% confidence
      interval 1.51 to 1.93) and the difference in mean height -0.232 SD score (-0.290
      to -0.174). Between large towns and rural areas the odds ratio for low birth
      weight adjusted for deprivation was 1.37 (1.23 to 1.53) and the difference in
      mean height -0.162 SD score (-0.214 to -0.110). Results for small towns were
      intermediate between large towns and rural areas. CONCLUSIONS: Inequalities in
      birth weight and height exist in all rural and urban settings between deprived
      and affluent areas. In addition, there is substantial disadvantage to living in
      urban areas compared with rural areas which results from social or environmental
      factors unrelated to current levels of deprivation.

PMID- 8281088
TI  - Guillain-Barre syndrome after exogenous gangliosides in Italy.

PMID- 8281089
TI  - Are clinicians interested in up to date reviews of effective care?

PMID- 8281090
TI  - How valuable is feedback of information on hospital referral patterns?
AB  - OBJECTIVES: To determine general practitioners' responses to and explanations for
      variation in rates of referral to hospital and how feedback of data on rates of
      referral could be used to facilitate practices in auditing their own referral
      behaviour. DESIGN: Visits by audit facilitators to general practices after
      feedback of details of rates of referral to hospital derived from annual reports
      in general practice. SETTING: 92 general practices in East Anglia. RESULTS:
      General practitioners judged that access to specialist care, the individual skill
      of general practitioners, patient demand, and fear of litigation were major
      determinants of referral behaviour. Because there was widespread scepticism about
      the accuracy of the data on which the feedback was based and because there is no
      clear relation between rates of referral and quality of care, it was extremely
      difficult to encourage doctors to use the feedback as a basis for auditing their
      own hospital referrals. CONCLUSION: If general practitioners are to contribute
      meaningfully to monitoring future changes in referral patterns it will be
      essential to develop reliable information systems in which doctors have
      confidence. Furthermore, audits need to be based on analysis of clinical cases
      rather than on rates of referral.

PMID- 8281091
TI  - Understanding variation in rates of referral among general practitioners: are
      inappropriate referrals important and would guidelines help to reduce rates?
AB  - OBJECTIVES: To determine the extent to which variation in rates of referral among
      general practitioners may be explained by inappropriate referrals and to estimate
      the effect of implementing referral guidelines. SETTING: Practices within
      Cambridge Health Authority and Addenbrooke's Hospital, Cambridge. MAIN OUTCOME
      MEASURES: Data on practice referral rates from hospital computers, inappropriate
      referrals as judged by hospital consultants, and inappropriate referrals as
      judged against referral guidelines which had been developed locally between
      general practitioners and specialists. Effect of referral guidelines on referral
      patterns as judged by general practitioners using the guidelines in clinical
      practice. RESULTS: There was 2.5-fold variation in referral rates among general
      practices. According to the specialists, 9.6% (95% confidence interval 6.4% to
      12.9%) of referrals by general practitioners and 8.9% (2.6% to 15.2%) of
      referrals from other specialists were judged possibly or definitely
      inappropriate. Against locally determined referral guidelines 15.9% of referrals
      by general practitioners were judged possibly inappropriate (11.8% to 20.0%).
      Elimination of all possibly inappropriate referrals could reduce variation in
      practice referral rates only from 2.5-fold to 2.1-fold. An estimate of the effect
      of using referral guidelines for 60 common conditions in routine general practice
      suggested that application of guidelines would have been unlikely to reduce rates
      of referral in hospital (95% confidence interval -4.5% to 8.6% of consultations
      resulting in referral). CONCLUSION: The variation in referral rates among general
      practitioners in Cambridge could not be explained by inappropriate referrals.
      Application of referral guidelines would be unlikely to reduce the number of
      patients referred to hospital.

PMID- 8281092
TI  - Helping women with premenstrual syndrome.

PMID- 8281093
TI  - ABC of emergency radiology. The skull.

PMID- 8281094
TI  - American and European recommendations for screening mammography in younger women:
      a cultural divide?
AB  - The American Cancer Society advocates mammography screening for all women from
      age 40, whereas in Europe it is not recommended for women below the age of 50.
      Randomised prospective studies have failed to show a significant benefit from
      screening women aged under 50 and five potentially harmful effects of screening
      should be considered: lead time, overdiagnosis, radiation exposure, false
      positive results, and cost. Younger women must be properly informed about the
      potential for harm as well as for benefit before screening.

PMID- 8281095
TI  - Clinical analysis of 100 medicolegal cases.
AB  - OBJECTIVE: To find the reasons for legal claims against hospital doctors. DESIGN:
      Prospective analysis of requests for medical opinion submitted by solicitors
      during 1984-93 on legal claims against hospital doctors. SUBJECTS: 100 successive
      cases: 98 from the United Kingdom and two from the Republic of Ireland. MAIN
      OUTCOME MEASURES: Principal underlying causes of claims. RESULTS: In 44 cases
      there was no serious clinical error. Of the 56 cases of clinical fault, seven
      were a failure of communication by doctors, 15 were an isolated error in
      otherwise good clinical management, 21 were errors that might not have occurred
      with better control of clinical practice (doctors exceeding their competence,
      poor clinical judgment, and poor teamwork), and 13 were major errors due to
      carelessness or incompetence. In 34 cases there was evidence of clinical fault
      that might escape clinical audit and medicolegal processes. Most of these legal
      claims have been or are likely to be withdrawn: only five plaintiffs have settled
      out of court, and 11 are pursuing their actions. CONCLUSIONS: To reduce the
      incidence of errors, hospital doctors should consult colleagues about difficult
      cases and specialists should maintain a broad interest in disease. The NHS
      clinical complaints procedure should be extended to cover potential claims, and
      serious cases should be subject to independent external assessment by experienced
      consultants.

PMID- 8281096
TI  - Laparoscopic nephrectomy.
AB  - Since the first clinical operation in June 1990 laparoscopic nephrectomy for
      benign renal disease has become widely accepted. Although the laparoscopic
      operation takes much longer than open surgery, there are considerable reductions
      in the length of postoperative hospital stay and the time taken to return to
      normal activities and to full recovery. Major complications were relatively
      common in early operations, but with more experience morbidity has been reduced.
      Laparoscopic nephrectomy for malignant renal disease is still controversial,
      largely because of the fear of release of malignant tissue into the abdominal
      cavity during the morcellation and retrieval of the diseased kidney. To prevent
      this, the kidney is removed intact through a 5-7 cm incision. Long term follow up
      is needed, however, before we will know whether the laparoscopic procedure is
      effective in preventing recurrence of cancer. New developments have improved
      various technical aspects of the operation, but stringent assessment of new
      techniques is necessary so that the medical community can decide which procedures
      should become routine practice.

PMID- 8281097
TI  - Anticoagulation in patients with atrial fibrillation. Not safe and not cheap.

PMID- 8281098
TI  - Anticoagulation in patients with atrial fibrillation. Underuse of warfarin is
      multifactorial.

PMID- 8281099
TI  - Anticoagulation in patients with atrial fibrillation. No consensus among doctors.

PMID- 8281100
TI  - Anticoagulation in patients with atrial fibrillation. Use of warfarin dependent
      on local services.

PMID- 8281101
TI  - Anticoagulation in patients with atrial fibrillation. Don't deny treatment to
      elderly people.

PMID- 8281102
TI  - Anticoagulation in patients with atrial fibrillation. Atrial fibrillation
      associated with aging.

PMID- 8281103
TI  - Informed consent in clinical trials. Should be comprehensive...

PMID- 8281104
TI  - Informed consent in clinical trials. ... it's the law.

PMID- 8281105
TI  - Informed consent in clinical trials. Doctors should admit uncertainty.

PMID- 8281106
TI  - Informed consent in clinical trials. Informed consent difficult in paediatric
      intensive care.

PMID- 8281107
TI  - Informed consent in clinical trials. Open discussion promotes trust.

PMID- 8281108
TI  - Informed consent in clinical trials. ... of the principles of clinical trials.

PMID- 8281109
TI  - Informed consent in clinical trials. Clinical judgement determines disclosure.

PMID- 8281110
TI  - Informed consent in clinical trials. Consent may not be possible.

PMID- 8281111
TI  - Informed consent in clinical trials. Strengthen ethical committees' role.

PMID- 8281112
TI  - Informed consent in clinical trials. Full consent may bias outcome of trials.

PMID- 8281113
TI  - Psychology of multiple allergies.

PMID- 8281114
TI  - Upper airway obstruction. Consider physical signs...

PMID- 8281115
TI  - Upper airway obstruction. ... and oxygen saturation.

PMID- 8281116
TI  - Giftedness.

PMID- 8281117
TI  - Social deprivation and health. Disease registers valuable if geographically
      defined.

PMID- 8281118
TI  - Social deprivation and health. Wealth redistribution has its price.

PMID- 8281119
TI  - The blood-brain barrier in vitro: the second decade.
AB  - Ever since the discovery of Paul Ehrlich (1885 Das Sauerstoff-bedurfnis des
      Organismus: Hirschwald, Berlin) about the restricted material exchange, existing
      between the blood and the brain, the ultimate goal of subsequent studies has been
      mainly directed towards the elucidation of relative importance of different
      cellular compartments in the peculiar penetration barrier consisting the
      structural basis of the blood-brain barrier (BBB). It is now generally agreed
      that, in most vertebrates, the endothelial cells of the central nervous system
      (CNS) are responsible for the unique penetration barrier, which restricts the
      free passage of nutrients, hormones, immunologically relevant molecules and drugs
      to the brain. After an era of studying with endogenous or exogenous tracers the
      unique permeability properties of cerebral endothelial cells in vivo, the next
      generation, i.e. the in vitro blood-brain barrier model system was introduced in
      1973. Recent advances in our knowledge of the BBB have in part been made by
      studying the properties and function of cerebral endothelial cells (CEC) with
      this in vitro approach. This review summarizes the results obtained on isolated
      brain microvessels in the second decade of its advent.

PMID- 8281120
TI  - The blood-brain barrier in vitro: recent progress.

PMID- 8281121
TI  - The same 15 kDa proteolipid subunit is a constituent of two different proteins in
      Torpedo, the acetylcholine releasing protein mediatophore and the vacuolar H+
      ATPase.
AB  - Using the monoclonal antibody 15K1, we have studied, at the cellular and
      subcellular levels, the distribution of a 15 kDa proteolipid, identified as the
      subunit of mediatophore, a presynaptic membrane protein able to release
      acetylcholine when activated by calcium. Aside from the electric lobe, the
      antigen distribution in the brain of Torpedo paralleled that of the synaptic
      vesicle antigen SV2 and did not appear to be related to that of acetylcholine and
      choline acetyltransferase. The 15 kDa proteolipid antigen was therefore present
      in all nerve endings and not restricted to cholinergic ones. At the
      ultrastructural level, on cholinergic nerve endings, the antigen was detected
      associated to synaptic vesicles and, to a lesser extent, to the presynaptic
      plasma membrane. Indeed, considering the high sequence homology between the
      mediatophore subunit (Birman et al., 1990) and the proteolipid subunit of the
      vacuolar type H+ ATPase, a major enzyme constituent of synaptic vesicles, this
      distribution was not surprising. To determine whether antibody 15K1 recognizes
      the vacuolar type H+ ATPase, we chose a non neuronal cell type which possesses a
      high content of this enzyme, the kidney proton secreting epithelial cells.
      Indeed, antibody 15K1 intensely labelled the apical plasma membrane of
      mitochondria rich epithelial cells in kidney tubules. A high density of the
      antigen was also found associated to intracellular membrane structures such as
      lysosomal multivesicular bodies, both in kidney epithelial cells and in
      electromotoneurons. The 15 kDa proteolipid antigen was associated with other
      vacuolar H+ ATPase subunits in kidney membranes which was not the case in
      presynaptic plasma membranes. This illustrates that the 15 kDa proteolipid
      antigen is a constituent of two different protein complexes, which exhibit very
      different functional properties.

PMID- 8281122
TI  - Selective changes of neurotransmitter receptors in middle-aged gerbil brain.
AB  - Age-related alterations in major neurotransmitter receptors and voltage dependent
      calcium channels were analyzed by receptor autoradiography in the gerbil brain.
      [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyladenosine (CHA), [3H]muscimol,
      [3H]MK-801, [3H]SCH 23390, [3H]naloxone, and [3H]PN200-110 were used to label
      muscarinic acetylcholine receptors, adenosine A1 receptors, gamma-aminobutyric
      acidA (GABAA) receptors, N-methyl-D-aspartate (NMDA) receptors, dopamine D1
      receptors, opioid receptors, and voltage dependent calcium channels,
      respectively. In middle-aged gerbils (16 months old), the hippocampus exhibited a
      significant elevation in [3H]QNB, [3H]MK-801, [3H]SCH 23390, [3H]naloxone, and
      [3H]PN200-110 binding, whereas [3H]CHA and [3H]muscimol binding showed a
      significant reduction in this area, compared with that of young animals (1
      month). On the other hand, the cerebellum showed a significant alteration in
      [3H]QNB, [3H]CHA, and [3H]naloxone binding and the striatum also exhibited a
      significant alteration in [3H]SCH 23390 and [3H]CHA binding in middle-aged
      gerbils. The neocortex showed a significant elevation only in [3H]CHA binding in
      middle-aged animals. The nucleus accumbens and thalamus also showed a significant
      alteration only in [3H]muscimol binding. However, the hypothalamus and substantia
      nigra exhibited no significant alteration in these bindings in middle-aged
      gerbils. These results demonstrate the age-related alterations of various
      neurotransmitter receptors and voltage dependent calcium channels in most brain
      regions. Furthermore, they suggest that the hippocampus is most susceptible to
      aging processes and is altered at an early stage of senescence.

PMID- 8281123
TI  - Chromatographic analysis of the enkephalin immunoreactivity in the nucleus locus
      coeruleus of the cat after local colchicine administration.
AB  - Cell bodies immunoreactive for methionine- and leucine-enkephalin are found in
      the area of the locus coeruleus (dorsolateral pons) of the cat after injection of
      colchicine in the ascending projections of the nucleus. Using radioimmunoassay
      procedures, it is shown that colchicine induces a significant increase in
      methionine- and leucine-enkephalin-immunoreactive material in this area of the
      brain. High pressure liquid chromatography analysis demonstrated that the
      immunoreactive materials were authentic methionine- and leucine-enkephalin. The
      methionine- and leucine-enkephalin patterns were identical in the colchicine
      injected and non-injected sides of the dorsolateral pons. It is suggested that,
      in this area of the brain, colchicine (i) does not significantly modify the
      processing of proenkephalin to form the pentapeptides methionine- and leucine
      enkephalin, and (ii) does not induce the appearance of new substances reactive to
      the enkephalin antisera employed.

PMID- 8281124
TI  - Characterization of K(+)-evoked [3H]D-aspartate outflow in the rat hippocampus in
      vitro.
AB  - The characteristics of K(+)-evoked outflow of [3H]D-aspartate, a glutamate
      release marker, were systematically investigated in the rat hippocampus, using 35
      mM K(+)-evoked [3H]noradrenaline outflow as a reference. Elevation of external K+
      concentrations increased [3H]D-aspartate outflow in a concentration-dependent
      manner both in slices and synaptosomes. In the absence of external Ca2+, K(+)
      evoked [3H]D-aspartate outflow was decreased by approx 60% in synaptosomes and
      80% in slices. However, elimination of external Ca2+ in the presence of 2 mM EGTA
      significantly reduced only 100 mM K(+)-evoked outflow, both in slices and
      synaptosomes. In the absence of external Ca2+, 35 mM K(+)-evoked
      [3H]noradrenaline outflow was abolished even when EGTA was present in the
      solution. Furthermore, the Ca(2+)-channel blockers omega-conotoxin (10 nM) and
      nifedipine (0.5 microM) did not significantly reduce K(+)-evoked [3H]D-aspartate
      outflow; [3H]noradrenaline outflow, however, was reduced by more than one third
      by omega-conotoxin. Finally [3H]D-aspartate overflow was insensitive to
      tetrodotoxin (0.5 microM) both in synaptosomes and in slices, while that of
      [3H]noradrenaline was significantly reduced in slices. It is concluded that (1)
      [3H]D-aspartate outflow is partly Ca(2+)-dependent; (2) differences between K(+)
      evoked [3H]D-aspartate and [3H]noradrenaline outflow include sensitivity to
      stimulation by EGTA, to Ca(2+)-channel blockers and to tetrodotoxin. Some of
      these discrepancies may be ascribed to the existence of a cytosolic, Ca(2+)
      independent pool of releasable glutamate and [3H]D-aspartate. These observations
      pose some problems as to the experimental approach for the study of Ca(2+)
      dependent [3H]D-aspartate release.

PMID- 8281125
TI  - The effects of 6-hydroxydopamine and oxidative stress on the level of brain
      metallothionein.
AB  - Oxidative stress, resulting either from excess generation or reduced scavenging
      of free radicals, has been proposed to play a role in damaging striatal neurons
      in Parkinson's disease. Since metallothionein is able to regulate the
      intracellular redox potential, we have undertaken a group of experiments to see
      whether or not 6-hydroxydopamine, which generates free radicals and is toxic to
      dopaminergic neurons, could alter the level of zinc and metallothionein. 6
      Hydroxydopamine (8 micrograms in 4 microliters 0.02% ascorbic acid) reduced the
      level of zinc and metallothionein in the striatum but not other brain regions
      tested. Dopamine plus selegiline increased the synthesis of metallothionein in
      Chang cells as judged by enhanced incorporation of [35S]cysteine into
      metallothionein. The effect of dopamine was selective, in that dopamine could not
      stimulate the synthesis of metallothionein in neuroblastoma IMR-32 cells, which
      are devoid of dopaminergic receptors. The effect of dopamine in stimulating the
      synthesis of metallothionein was similar to that of zinc, known to generate the
      synthesis of metallothionein, and to that of H2O2 and FeS04, known to generate
      free radicals. The results of these experiments provide additional evidence that
      zinc or zinc metallothionein are altered in conditions where oxidative stress has
      taken place.

PMID- 8281126
TI  - Induction of glucose regulated protein (grp78) and inducible heat shock protein
      (hsp70) mRNAs in rat brain after kainic acid seizures and focal ischemia.
AB  - Specific probes were obtained using PCR cloning from rat brain for the 78 kDa
      glucose regulated (grp78), inducible 72 kDa (hsp70) as well as constitutive 73
      kDa (hsc73) heat shock mRNAs. Grp78 and hsc73 were expressed in normal rat brain
      whereas hsp70 was not. Subcutaneous injection kainic acid (10 mg/kg) produced
      seizures and induced all three mRNAs. The induction of grp78 and hsp70 mRNAs
      occurred within 2 h, peaked between 6-8 h, persisted for 48 h, and returned to
      control levels by 72 h. Expression of the grp78 and hsp70 mRNAs after focal
      ischemia progressively increased with occlusion durations from 15-120 min in the
      cerebral cortex. Though grp78 and hsp70 mRNAs were induced modestly in the
      striatum by 15 min of ischemia, longer durations of ischemia were characterized
      by little change in the grp78 mRNA levels and relatively lower levels of hsp70
      expression. This result indicates that progressive increases in the duration of
      ischemia in brain, prior to infarction, may produce proportional increases in
      transcription of the heat shock genes. However, once the duration of ischemia is
      long enough to produce infarction, this severely limits the availability of ATP
      which blocks transcription of the heat shock genes. In conclusion, concurrent
      induction of the heat shock genes suggests that kainic acid seizures and focal
      ischemia induce several different stress responses in brain cells caused by
      denaturation of proteins, changes of protein synthesis, and changes of protein
      glycosylation.

PMID- 8281127
TI  - Homologies and disparities of glutamate receptors: a critical analysis.
AB  - Based on analysis of aligned amino acid sequences the following statements are
      made: (i) There is evolutionary homology between the N-terminal extracellular
      region of ionotropic Glutamate receptors/Kainate Binding Proteins and a family of
      procaryote amino acid binding proteins. (ii) Homology of the N-terminal
      extracellular domain of the metabotropic glutamate receptors with a family of
      receptors with a guanylate cyclase intracellular domain appears to be valid.
      (iii) There is no evidence for homology between the N-terminal extracellular
      domain of the nicotinic Acetylcholine, GABA, Glycine and 5HT3 receptors and that
      of the ionotropic Glutamate receptors/Kainate Binding proteins. (iv) The proposal
      of homology for the N-terminal extracellular domain of metabotropic Glutamate
      receptors and that of ionotropic Glutamate receptors does not appear to hold.

PMID- 8281128
TI  - Analytical expression of the purine/pyrimidine codon probability after and before
      random mutations.
AB  - Recently, we proposed a new model of DNA sequence evolution (Arques and Michel.
      1990b. Bull. math. Biol. 52, 741-772) according to which actual genes on the
      purine/pyrimidine (R/Y) alphabet (R = purine = adenine or guanine, Y = pyrimidine
      = cytosine or thymine) are the result of two successive evolutionary genetic
      processes: (i) a mixing (independent) process of non-random oligonucleotides
      (words of base length less than 10: YRY(N)6, YRYRYR and YRYYRY are so far
      identified; N = R or Y) leading to primitive genes (words of several hundreds of
      base length) and followed by (ii) a random mutation process, i.e.,
      transformations of a base R (respectively Y) into the base Y (respectively R) at
      random sites in these primitive genes. Following this model the problem
      investigated here is the study of the variation of the 8 R/Y codon probabilities
      RRR, ..., YYY under random mutations. Two analytical expressions solved here
      allow analysis of this variation in the classical evolutionary sense (from the
      past to the present, i.e., after random mutations), but also in the inverted
      evolutionary sense (from the present to the past, i.e., before random mutations).
      Different properties are also derived from these formulae. Finally, a few
      applications of these formulae are presented. They prove the proposition in
      Arques and Michel (1990b. Bull. math. Biol. 52, 741-772), Section 3.3.2, with the
      existence of a maximal mean number of random mutations per base of the order 0.3
      in the protein coding genes. They also confirm the mixing process of
      oligonucleotides by excluding the purine/pyrimidine contiguous and alternating
      tracts from the formation process of primitive genes.

PMID- 8281129
TI  - A Cayley tree immune network model with antibody dynamics.
AB  - A Cayley tree model of idiotypic networks that includes both B cell and antibody
      dynamics is formulated and analysed. As in models with B cells only, localized
      states exist in the network with limited numbers of activated clones surrounded
      by virgin or near-virgin clones. The existence and stability of these localized
      network states are explored as a function of model parameters. As in previous
      models that have included antibody, the stability of immune and tolerant
      localized states are shown to depend on the ratio of antibody to B cell lifetimes
      as well as the rate of antibody complex removal. As model parameters are varied,
      localized steady-states can break down via two routes: dynamically, into chaotic
      attractors, or structurally into percolation attractors. For a given set of
      parameters percolation and chaotic attractors can coexist with localized
      attractors, and thus there do not exist clear cut boundaries in parameter space
      that separate regions of localized attractors from regions of percolation and
      chaotic attractors. Stable limit cycles, which are frequent in the two-clone
      antibody B cell (AB) model, are only observed in highly connected networks. Also
      found in highly connected networks are localized chaotic attractors. As in
      experiments by Lundkvist et al. (1989. Proc. natn. Acad. Sci. U.S.A. 86, 5074
      5078), injection of Ab1 antibodies into a system operating in the chaotic regime
      can cause a cessation of fluctuations of Ab1 and Ab2 antibodies, a phenomenon
      already observed in the two-clone AB model. Interestingly, chaotic fluctuations
      continue at higher levels of the tree, a phenomenon observed by Lundkvist et al.
      but not accounted for previously.

PMID- 8281130
TI  - Memory in idiotypic networks due to competition between proliferation and
      differentiation.
AB  - A model employing separate dose-dependent response functions for proliferation
      and differentiation of idiotypically interacting B cell clones is presented. For
      each clone the population dynamics of proliferating B cells, non-proliferating B
      cells and free antibodies are considered. An effective response function, which
      contains the total impact of proliferation and differentiation at the fixed
      points, is defined in order to enable an exact analysis. The analysis of the
      memory states is restricted in this paper to a two-species system. The conditions
      for the existence of locally stable steady states with expanded B cell and
      antibody populations are established for various combinations of different field
      response functions (e.g. linear, saturation, log-bell functions). The stable
      fixed points are interpreted as memory states in terms of immunity and tolerance.
      It is proven that a combination of linear response functions for both
      proliferation and differentiation does not give rise to stable fixed points.
      However, due to competition between proliferation and differentiation saturation
      response functions are sufficient to obtain two memory states, provided
      proliferation precedes differentiation and also saturates earlier. The use of log
      bell-shaped response functions for both proliferation and differentiation gives
      rise to a "mexican-hat" effective response function and allows for multiple (four
      to six) memory states. Both a primary response and a much more pronounced
      secondary response are observed. The stability of the memory states is studied as
      a function of the parameters of the model. The attractors lose their stability
      when the mean residence time of antibodies in the system is much longer than the
      B cells' lifetime. Neither the stability results nor the dynamics are
      qualitatively changed by the existence of non-proliferating B cells: memory
      states can exist and be stable without non-proliferating B cells. Nevertheless,
      the activation of non-proliferating B cells and the competition between
      proliferation and differentiation enlarge the parameter regime for which stable
      attractors are found. In addition, it is shown that a separate activation step
      from virgin to active B cells renders the virgin state stable for any choice of
      biologically reasonable parameters.

PMID- 8281131
TI  - Finding the lowest free energy conformation of a protein is an NP-hard problem:
      proof and implications.
AB  - The protein folding problem and the notion of NP-completeness and NP-hardness are
      discussed. A lattice model is suggested to capture the essence of protein
      folding. For this model we present a proof that finding the lowest free energy
      conformation belongs to the class of NP-hard problems. The implications of the
      proof are discussed and we suggest that the natural folding process cannot be
      considered as a search for the global free energy minimum. However, we suggest an
      explanation as to why, for many proteins, the native functional conformation may
      coincide with the lowest free energy conformation.

PMID- 8281132
TI  - Complexity of protein folding.
AB  - It is believed that the native folded three-dimensional conformation of a protein
      is its lowest free energy state, or one of its lowest. It is shown here that both
      a two- and three-dimensional mathematical model describing the folding process as
      a free energy minimization problem is NP-hard. This means that the problem
      belongs to a large set of computational problems, assumed to be very hard
      ("conditionally intractable"). Some of the possible ramifications of this result
      are speculated upon.

PMID- 8281133
TI  - Adverse events temporally associated with immunizing agents--1991 report.

PMID- 8281134
TI  - Yet another skin defect, Darier's disease, maps to chromosome 12q.

PMID- 8281135
TI  - The utrophin and dystrophin genes share similarities in genomic structure.
AB  - Utrophin and dystrophin are highly homologous proteins which are reciprocally
      expressed in DMD (Duchenne muscular dystrophy) muscle. The remarkable similarity
      of these proteins suggests that they may play a similar cellular role in some
      circumstances; if this were the case then utrophin may be capable of replacing
      dystrophin in DMD patients. In this paper we show that the genomic structure of
      the utrophin gene is similar to the dystrophin gene, further exemplifying the
      relatedness of the two genes and their gene products. We have constructed a 1.25
      Mb contig of eight yeast artificial chromosome (YAC) clones covering the utrophin
      gene located on chromosome 6q24. Utrophin is encoded by multiple small exons
      spanning approximately 900 kb. The distribution of exons within the genomic DNA
      has similarities to that of the dystrophin gene. In contrast to dystrophin, the
      utrophin gene has a long 5' untranslated region composed of two exons and a
      cluster of unmethylated, rare-cutting restriction enzyme sites at the 5' end of
      the gene. Similarities between the genomic structure suggest that utrophin and
      dystrophin arose through an ancient duplication event involving a large region of
      genomic DNA.

PMID- 8281136
TI  - Characteristic mRNA abnormality found in half the patients with severe
      haemophilia A is due to large DNA inversions.
AB  - Surprisingly half of all severe haemophilia A patients have no mutation in the
      promoter, coding sequences and normal RNA processing signals of the factor VIII
      gene. Instead they manifest a unique mRNA defect that prevents the amplification
      of the message across the boundary between exon 22 and 23. This locates the
      defect to internal regions of intron 22. Novel sequences 3' to exon 22 were
      isolated from the 9 available patients with the above abnormality by combining
      RACE and vectorette amplifications on trace amounts of mRNA. This showed that
      exons 1-22 of the factor VIII mRNA had become part of a hybrid message containing
      new multi exonic sequences expressed in normal cells. The novel sequences were
      not located in a YAC covering the whole factor VIII gene. Southern blots from
      patients probed by novel sequences and clones covering intron 22 showed no
      obvious abnormalities. This suggested inversions involving intron 22 repeated
      sequences. Screening of 3 YAC libraries with the novel sequences located them at
      least 200 kb telomeric (5') to factor VIII and pulsed field gel analysis detected
      abnormal bands in patients. This demonstrates that the mutations in the patients
      are inversions of long DNA regions possibly involving the repeated sequences and
      occurring at the surprising rate of approximately 4 x 10(-6) per gene per gamete
      per generation.

PMID- 8281137
TI  - Cosegregation of missense mutations of the luteinizing hormone receptor gene with
      familial male-limited precocious puberty.
AB  - Familial male-limited precocious puberty is a male-limited autosomal dominant
      condition. It is characterized by increased testosterone synthesis in the absence
      of testicular stimulation by luteinizing hormone (LH). We hypothesised that an
      abnormal configuration of the LH receptor might autonomously activate G protein
      coupling, and thereby cause the overproduction of testosterone in this condition.
      To test this hypothesis, we screened for mutations in a part of the LH receptor
      gene that is important for G protein binding. DNA sequence variation was detected
      in 2 out of 5 families with male-limited precocious puberty by the single strand
      conformation polymorphism technique. Direct sequencing demonstrated different
      single nucleotide substitutions in the sixth transmembrane region of the LH
      receptor gene. The mutations cosegregated with the disorder in both families (lod
      score 5.76 without recombination). Both mutations cause an amino acid
      substitution in the sixth transmembrane domain, close to the C-terminal portion
      of the third cytoplasmatic loop, a region which is important for the binding of G
      proteins. We conclude that familial male-limited precocious puberty cosegregates
      with missense mutations in the LH receptor gene. These findings support the
      hypothesis that increased activity of the LH receptor is the pathogenetic
      mechanism that causes the abnormal pubertal development in this condition.

PMID- 8281138
TI  - A combined genetic and radiation hybrid map surrounding the Treacher Collins
      syndrome locus on chromosome 5q.
AB  - The distal region of chromosome 5q contains a large number of genes, including
      those implicated in a variety of Mendelian disorders. One of these, Treacher
      Collins syndrome (TCOF1), is an autosomal dominant disorder of craniofacial
      development the features of which include conductive hearing loss and cleft
      palate. Previous studies have localized the TCOF1 locus between D5S519 (proximal)
      and SPARC (distal). To more accurately define the genetic distance between these
      markers, and to extend a high resolution genetic map of 5q31-33 to include
      additional highly informative markers, 15 loci (including polymorphisms for 4
      known genes) were mapped through the Centre d'Etude du Polymorphisme Humain
      reference pedigrees. The resulting genetic map encompasses 29 cM on the sex
      averaged map. To help integrate this linkage map with a physical map of the
      region, 13 loci from 5q31--33, including 6 genes, were used to construct a
      radiation hybrid map. As eight of the loci are common to both maps this has
      allowed us to combine the maps. The most likely location for the TCOF1 locus
      within this marker framework is in the D5S519-SPARC interval; a region estimated
      to be approximately 880 kb.

PMID- 8281139
TI  - Androgen receptor gene mutation in male breast cancer.
AB  - We screened thirteen male breast cancers for the presence of germline mutations
      in exons 2 and 3 encoding the DNA-binding domain of the androgen receptor. These
      two exons were amplified from genomic DNA extracted from patients' white blood
      cells. In one of these thirteen patients, single strand conformation polymorphism
      and direct sequencing detected a guanine-adenine point mutation at nucleotide
      2185 that changes Arg608 into Lys in a highly conserved region of the second zinc
      finger of the androgen receptor. This mutation occurred in a 38 year old man with
      partial androgen insensitivity syndrome and normal androgen-binding capacity in
      cultured genital skin fibroblasts. To our knowledge, only one germline Arg to Gln
      androgen receptor gene mutation has been previously reported at position 607 in
      male breast cancer. This androgen receptor mutation along with the Arg608 into
      Lys mutation we describe, suggests that this genetic abnormality is not
      fortuitous: a decrease in androgen action within the breast cells could account
      for the development of male breast cancer by the loss of a protective effect of
      androgens on these cells. Activation of estrogen regulated genes by the change of
      DNA-binding characteristics of the mutant androgen receptor cannot, however, be
      ruled out.

PMID- 8281140
TI  - A single-base substitution in exon 6 of the androgen receptor gene causing
      complete androgen insensitivity: the mutated receptor fails to transactivate but
      binds to DNA in vitro.
AB  - A single-base substitution in the coding region of the androgen receptor (AR)
      gene caused complete androgen insensitivity in a patient with 46,XY karyotype.
      The mutation was a T-to-G transition in exon 6 and changed the codon 807 from ATG
      (methionine) to AGG (arginine) in the hormone-binding domain of the protein. The
      mutation was inserted into the wild-type human AR cDNA and the resulting cDNA
      expressed in CV-1 cells. Native and mutated AR proteins synthesized in recipient
      cells had identical molecular masses. Ligand-binding activity of the mutant
      receptor was less than 5% of that of the wild-type AR. The mutant's interaction
      with an androgen-response element in vitro was identical to that of the native
      aporeceptor; however, it did not transactivate a reporter gene construct in
      transfected CV-1 cells. Androgen insensitivity in our patient was thus due to
      altered structure of the receptor's steroid-binding region, which prevented the
      mutated AR from gaining a transcriptionally active form in vivo.

PMID- 8281141
TI  - Mutation screening of complete fibrillin-1 coding sequence: report of five new
      mutations, including two in 8-cysteine domains.
AB  - Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue
      disorder characterized by cardiovascular, ocular and skeletal manifestations.
      Previously, mutations in the fibrillin-1 gene on chromosome 15 (FBN1) have been
      reported to cause MFS. We have now screened 44 probands with MFS or related
      phenotypes for alterations in the entire fibrillin coding sequence (9.3 kb) by
      single strand conformation analysis. We report four unique mutations in the
      fibrillin gene of unrelated MFS patients. One is a 17 bp deletion and three are
      missense mutations, two of which involve 8-cysteine motifs. Another missense
      mutation was found in two unrelated individuals with annuloaortic ectasia but was
      also present in unaffected relatives and controls from various ethnic
      backgrounds. By using allele-specific oligonucleotide hybridization, we screened
      65 unrelated MFS patients, 29 patients with related phenotypes and 84 control
      individuals for these mutations as well as for a previously reported mutation and
      two polymorphisms. Our results suggest that most MFS families carry unique
      mutations and that the fibrillin genotype is not the sole determinant of the
      connective tissue phenotype.

PMID- 8281142
TI  - Genetic analysis of the BRCA1 region in a large breast/ovarian family: refinement
      of the minimal region containing BRCA1.
AB  - We have analyzed a single multi-affected breast/ovarian cancer pedigree (BOV3)
      and have shown consistent inheritance of markers on chromosome 17q with the
      disease confirming that this family is due to the BRCA1 gene. Analysis of 17q
      haplotypes shows a recombination event in a bilateral breast cancer case which
      suggests that the BRCA1 gene lies distal to D17S857; D17S857 is thus the new
      proximal boundary for the region containing BRCA1. Combining this information
      with previously published mapping information suggests that BRCA1 is contained in
      a region estimated at 1-1.5 Mb in length. All seven breast tumour/blood pairs
      examined from this family show loss of heterozygosity in the tumours. The allel
      retained in each tumour was from the disease-bearing chromosome implicating BRCA1
      as a tumour suppressor gene. We have sequenced the 17 beta-oestradiol
      dehydrogenase genes (EDH17B1 and EDH17B2) which have been suggested as candidate
      genes for BRCA1 in four members of this family. No germline mutations were
      detected.

PMID- 8281143
TI  - The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic
      organization.
AB  - Mice carrying a retroviral insert in both alleles of the Mpv17 gene develop
      glomerulosclerosis and nephrotic syndrome at young age. Thus, the Mpv17 gene is a
      recessive disease gene in mice and this mouse strain is a potential animal model
      for glomerular diseases in man. We here describe the isolation and analysis of a
      human homolog of this gene. By interspecies hybridisation cDNA clones
      representing a single RNA species were isolated from human liver. Sequence
      analysis revealed over 90% identify in a region coding for a protein of 176 amino
      acids and unknown function in both species. Cloning of the genomic locus revealed
      a single copy gene which we mapped to the short arm of chromosome 2 at band 2p23
      p21. Determination of the intron-exon structure and the junction sequences
      enabled us to establish a PCR based procedure to isolate the coding region from
      human genomic DNA. Thus, it is now possible to analyse patients suffering from
      candidate diseases on the basis of a blood sample if biopsy material is not
      available.

PMID- 8281144
TI  - Expression and processing of human ornithine-delta-aminotransferase in
      Saccharomyces cerevisiae.
AB  - Ornithine-delta-aminotransferase catalyzes the conversion of ornithine to
      glutamate-gamma-semialdehyde. In humans, deficiency of this mitochondrial matrix
      enzyme results in the progressive blinding disorder, gyrate atrophy of the
      choroid and retina. To explore yeast as an expression system, we introduced a
      cDNA encoding human ornithine-delta-aminotransferase into an ornithine
      aminotransferase-deficient strain of Saccharomyces cerevisiae. The human enzyme
      was expressed at high levels, with activity 20-fold greater than that of wild
      type yeast and 10-fold higher than in human fibroblasts. Although the normal
      location of ornithine-delta-aminotransferase in S. cerevisiae is cytosolic, human
      ornithine-delta-aminotransferase expressed in S. cerevisiae was localized to the
      mitochondrial matrix with correct proteolytic processing of its mitochondrial
      leader sequence. Despite this anomalous location in yeast, human ornithine-delta
      aminotransferase complemented the phenotype of the mutant strain, restoring its
      ability to utilize ornithine as a sole nitrogen source. We also expressed a
      vitamin B6-responsive missense allele of ornithine-delta-aminotransferase (V332M)
      and showed that the biochemical phenotype of this allele is easily demonstrated
      confirming the usefulness of this system for examining mutations causing gyrate
      atrophy.

PMID- 8281145
TI  - Cloning and expression of cDNA encoding human galactocerebrosidase, the enzyme
      deficient in globoid cell leukodystrophy.
AB  - Globoid cell leukodystrophy (Krabbe disease) is an autosomal recessive disorder
      resulting from the deficiency of galactocerebrosidase (GALC) activity. GALC is
      responsible for the lysosomal catabolism of galactosylceramide, a major lipid in
      myelin, kidney and epithelial cells of small intestine and colon. We describe the
      molecular cloning of human GALC cDNA and its expression in COS-1 cells.
      Degenerate PCR primers, derived from N-terminal amino acid sequence from the 51
      kDa band from human brain, were used to amplify cat testes RNA, and the resulting
      product was used to screen human testes and brain libraries. Two overlapping
      clones contained the total protein coding region, while additional clones and PCR
      amplification were needed to obtain the complete 3' end of the cDNA. The 3795 bp
      obtained include 47 bp 5' to the initiation start site, 2007 bp of open reading
      frame (coding for 669 amino acids), and 1741 bp of 3' untranslated sequence.
      Modification of the sequence surrounding the initiation codon to one more
      favorable for expression, resulted in a 6-fold increase in GALC activity in
      transfected COS-1 cells. The isolation of this clone will permit investigations
      into the causes for GALC deficiency in humans and available animal models,
      development of more accurate tests for patient and carrier identification, and
      evaluation of methods for effectively treating GALC deficiency, initially using
      the animal models.

PMID- 8281146
TI  - DNA-based immunization induces continuous secretion of hepatitis B surface
      antigen and high levels of circulating antibody.
AB  - The possibility of inducing an immune response to a protein expressed directly
      from an introduced gene represents an alternative to classic vaccination. We
      evaluated the ability of plasmid-based eukaryotic expression vectors to produce
      the Hepatitis B surface antigen (HBsAg) after injection of pure DNA into mouse
      tibialis anterior muscles. DNA was injected into either normal mature muscle, or
      regenerating muscle following cardiotoxin-induced degeneration. The sera obtained
      from these animals contained significant levels of HBsAg as early as 10 days
      after gene transfer, at which time low levels of antibodies to HBsAg (anti-HBsAg)
      were already present. Between 15-60 d after DNA transfer, serum levels of anti
      HBsAg steadily increased whereas those for HbsAg fell, most likely due to the
      neutralizing effect of the antibodies. Analysis of proportions of HBs
      seropositive mice showed that within 2 wk of injection of 100 micrograms pCMV-HBs
      in regenerating muscle, 91% of the mice were seropositive [defined as having more
      than 1 milli-International Unit/ml (mIU/ml) of anti-HBsAg]. Even at that early
      time, 68% had titers of anti-HBsAg greater than 10 mlU/ml, a level that is
      recognized as being sufficient in humans to confer protection against natural
      Hepatitis B virus infection. The proportion of seropositive animals rose to 95%
      by 4 wk, and 100% by 8 wk, at which time all mice had greater than 100 mIU anti
      HBsAg in their sera. We have thus demonstrated that direct intramuscular
      injection of a plasmid vector encoding the HBsAg will give rise to secretion of
      the viral surface protein into the circulation which leads to an appropriate
      antibody response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281147
TI  - A 45,X male with an X;Y translocation: implications for the mapping of the genes
      responsible for Turner syndrome and X-linked chondrodysplasia punctata.
AB  - In a male patient with a 45,X karyotype, the terminal part of the Y chromosome
      short arm was translocated as a single block on to the X chromosome. This
      rearranged X chromosome was, in every regard, the same as that present in XX
      males resulting from an abnormal X-Y interchange. Correlations between the
      phenotype of this patient and the extent of the deletions on the X and Y
      chromosomes allowed us to map the genes responsible for most features of the
      Turner syndrome between DXS432 and Xqter on the X chromosome, and the homologous
      Y genes either on Yp in interval 4 or on Yq. The molecular analysis of this X-Y
      translocation allowed us also to reduce the interval for the X-linked recessive
      chondrodysplasia punctata gene to a 1.5 Mb interval between DXS432 and DXS31.

PMID- 8281148
TI  - Construction of a transcription map of a 300 kb region around the human G6PD
      locus by direct cDNA selection.
AB  - A transcription map covering a 300 kb region around the G6PD gene in the human
      Xq28 region was constructed by the direct cDNA selection method and the analysis
      of the resulting region-specific enriched cDNA sublibrary. Seven new genes and
      two loci of endogenous retrovirus HERV-K were identified. The distribution of the
      genes across the region is strongly non-uniform and follows the non-uniform
      distribution of GpG islands in the area. While one of the novel genes was found
      to be highly homologous to bovine smg p25A GDP-dissociation inhibitor, the
      remaining genes did not detect any homology to known genes. The analysis of
      region-specific cDNA sublibraries represents a simple, rapid and efficient tool
      for the generation of a regional transcription map.

PMID- 8281149
TI  - Iduronate-2-sulfatase gene mutations in 16 patients with mucopolysaccharidosis
      type II (Hunter syndrome).
AB  - Mutations of the iduronate-2-sulfatase gene were identified in 16 patients with
      mucopolysaccharidosis type II (Hunter syndrome). Together with another 10 cases
      reported by us earlier it emerges that about 20% of the patients have deletions
      of the whole gene or other major structural alterations. One, two or three base
      pair deletions are found in about 23% of the cases while the remaining about 57%
      carry point mutations predicting amino acid replacement, premature termination of
      translation, or aberrant splicing. Molecular analysis of mRNA in splice site
      mutants showed that these latter defects frequently resulted in use of cryptic
      splice sites in exons or introns. 62% of the small deletions and point mutations
      have occurred in 3 of the 9 iduronate-2-sulfatase gene exons. Knowledge of the
      primary genetic defect allows fast and reliable carrier detection and prenatal
      diagnosis as well as insight into the relationship between genotype and
      phenotype.

PMID- 8281150
TI  - Point mutations at the carboxy terminus of the human dystrophin gene:
      implications for an association with mental retardation in DMD patients.
AB  - Duchenne and Becker muscular dystrophies (DMD/BMD) are caused by mutations in the
      human dystrophin gene. About two-thirds of DMD/BMD patients exhibit gross
      rearrangements in the gene whereas the mutations in the remaining one third are
      thought to be point mutations or minor structural lesions. By means of various
      progressive PCR-based techniques hitherto a number of point mutations has been
      described that in most cases should cause premature translational termination.
      These data indicate a particular functional importance for the C-terminal region
      of dystrophin and consequently for its gene products Dp 71 and Dp 116. To screen
      for microheterogeneities in this gene region we applied PCR-SSCP analysis to
      exons 60-79 of twenty-six DMD/BMD patients without detectable deletions. The
      study identified seven point mutations and one intron polymorphism. Six point
      mutations, found in DMD patients, should cause premature translational
      termination. One point mutation, identified in a BMD patient, results in an amino
      acid exchange. Five of the DMD patients bearing a point mutation are mentally
      retarded suggesting that a disruption of the translational reading frame in the C
      terminal region is associated with this clinical finding in DMD cases. Therefore
      our data raise the possibility, that Dp 71 and/or Dp 116, the C-terminal
      translational products of dystrophin, may be causally involved in cases of mental
      retardation that are associated with DMD.

PMID- 8281151
TI  - A housekeeping type promoter, located in the 3' region of the Duchenne muscular
      dystrophy gene, controls the expression of Dp71, a major product of the gene.
AB  - The 70.8 kDa protein product of the distal part of the giant Duchenne muscular
      dystrophy (DMD) gene, Dp71, is expressed in many cell types and tissues. Anchored
      PCR, primer extension and functional analysis of transfected constructs were used
      to determine the 5' end of the mRNA and characterize the promoter of this major
      DMD gene product. The 5' untranslated region (5'UTR) of Dp71 is transcribed from
      a single exon; the promoter does not contain a TATA box, and has a very high GC
      content and several potential Sp1 binding sites. It is located more than 2000 kb
      3' to the muscle and brain type dystrophin promoters and only 150 kb from the 3'
      end of the gene, suggesting that in most DMD patients the expression of Dp71 is
      unaffected.

PMID- 8281152
TI  - Myotonic dystrophy kinase is a component of neuromuscular junctions.
AB  - The clinical manifestation of myotonic dystrophy (DM) is correlated to the extent
      of expansion of an unstable [CTG]n DNA motif. Recent studies have demonstrated
      that this trinucleotide motif forms part of the last, 3' untranslated exon of a
      gene which potentially encodes multiple protein isoforms of a serine/threonine
      protein kinase (myotonic dystrophy protein kinase, DM-PK). We report here on the
      development of antisera against synthetic DM-PK peptide antigens and their use in
      biochemical and histochemical studies. Immunoreactive DM-kinase protein of 53 kD
      is present at low levels in skeletal and cardiac muscle extracts of DM patients
      and normal controls. Immunohistochemical staining revealed that DM-PK is
      localised prominently at sites of neuromuscular and myotendinous junctions (NMJs
      and MTJs) of human and rodent skeletal muscles. Furthermore, very low levels of
      immunoreactive DM-PK protein are present in the sarcoplasm of predominantly type
      I fibres in various muscles. Strikingly, presence of the protein can also be
      demonstrated for NMJs of muscular tissues of adult and congenital cases of DM,
      with no gross changes in structural organisation. Our findings provide a basis
      for further characterisation of the role of the kinase in protein assembly
      processes or signal mediation at synaptic sites and ultimately for the
      understanding of the complex pathophysiology of DM.

PMID- 8281153
TI  - Genomic organization of the gene encoding the p65 subunit of NF-kappa B: multiple
      variants of the p65 protein may be generated by alternative splicing.
AB  - Transcription factor NF-kappa B represents a family of closely related homo- and
      heterodimeric factors. The most abundant form of NF-kappa B is the p50/p65
      heterodimer. We determined the complete genomic structure of the human gene and a
      partial structure of the mouse gene encoding p65. The human gene consists of ten
      exons and spans about 8.1 kbp of DNA. The exon-intron organization in the rel
      homology domain (exons 2 to 7) is conserved when compared to human and turkey c
      rel, strengthening the evolutionary relationship between p65 and c-rel. The
      lengths of the corresponding introns 5 and 6 in the human and mouse p65 genes are
      not conserved. However, a surprisingly high degree of conservation of intron
      sequences was observed between both species. We show that the naturally occurring
      shorter variant of p65 (p65 delta) can be generated by alternative splicing of
      intron 6, not only in humans but also in mouse. In addition, the existence of
      another, as yet unknown splice variant of p65 is predicted.

PMID- 8281154
TI  - Regional assignment of 19 X-linked ESTs.
AB  - Subchromosomal localizations for 19 X-linked expressed sequence tags (ESTs) have
      been determined. Two ESTs are located in Xq28, adding two novel genes to this
      disease-rich region. The remaining ESTs are located primarily in the
      pericentromeric region, with most mapping to Xp11.1-p21.1. YAC and cosmid genomic
      clones have been isolated for several of these loci. Available cDNAs have been
      used to characterize the corresponding transcripts by Northern analysis in
      multiple human tissues.

PMID- 8281155
TI  - Molecular cytogenetic analysis of formalin-fixed, paraffin-embedded solid tumors
      by comparative genomic hybridization after universal DNA-amplification.
AB  - We present a technique which allows the detection and chromosomal localization of
      DNA sequence copy number changes in solid tumor genomes from frozen sections and
      paraffin embedded, formalin fixed specimens. Based on comparative genomic
      hybridization and on universal DNA amplification procedures this technique is
      possible even if only a few tumor cells are available. We demonstrate the
      feasibility of this method to visualize complete and partial chromosome gains and
      losses and gene amplifications in archived solid tumor samples.

PMID- 8281156
TI  - Functional evidence for a breast cancer growth suppressor gene on chromosome 17.
AB  - Rearrangements or deletions of chromosome 17 are the most frequently observed
      genetic changes identified in breast tumors. Molecular analyses suggest that in
      addition to the p53 gene on 17p13.1 there may be at least three other tumor
      suppressor genes on chromosome 17 involved in breast cancer. Regions of loss of
      heterozygosity (LOH) identified on 17p13.3 and 17q12-qter occur frequently in
      breast tumors, and the BRCA-1 gene has been mapped to 17q21 by genetic linkage
      analysis. Here we provide biological evidence for the presence of a growth
      suppressor gene(s) on chromosome 17 that results in the in vitro growth
      suppression of the p53 wild-type MCF 7 breast cancer cell line. We have
      introduced a normal chromosome 17 into MCF 7 cells by microcell-mediated
      chromosome transfer (MMCT), and demonstrate that cells growth arrest before 10 to
      12 population doublings. In contrast, the introduction of a normal chromosome 13
      had no effect upon growth of these cells either in vitro or in vivo. These data
      provide direct functional evidence for the presence of a growth suppressor
      gene(s) on chromosome 17, which is not p53, and which may represent one of
      several gene(s) that play a critical role in the development of breast cancer.

PMID- 8281157
TI  - Non-disjunction in human sperm: results of fluorescence in situ hybridization
      studies using two and three probes.
AB  - Fluorescence in situ hybridization using two or three probes was utilized to
      estimate the incidence of diploidy, the incidence of disomy for the sex
      chromosomes and chromosomes 16 and 18, and the proportion of Y- and X-chromosome
      bearing sperm, in a series of normal males. Our results demonstrate the
      importance of using an approach capable of distinguishing disomy from diploidy,
      as most donors had levels of diploidy higher than the disomy levels of individual
      chromosomes. Our analyses suggest the existence of chromosome-specific mechanisms
      of paternal non-disjunction, as sex chromosome disomy was approximately 1.5 times
      as common as disomy 16, and over two times as common as disomy 18. In studies of
      gametic sex ratio, we found little evidence for marked deviation from an expected
      1:1 ratio.

PMID- 8281158
TI  - Genetic heterogeneity for Duchenne-like muscular dystrophy (DLMD) based on
      linkage and 50 DAG analysis.
AB  - Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive (AR) muscular
      dystrophy which presents a clinical course indistinguishable from the Xp21
      Duchenne muscular dystrophy or DMD. Recently, Othmane et al., based on a linkage
      study with 13q12 markers in 3 highly inbred DLMD families from Tunisia, suggested
      that the gene for this myopathy lies in the pericentromeric region of chromosome
      13q. It is unknown if there is genetic heterogeneity causing the DLMD phenotype.
      Therefore, the aim of the present report is to describe the results of linkage
      analysis in 4 Brazilian DLMD families with 13q12 markers (D13S115 and D13S120),
      which were also tested for 50DAG. It was possible to exclude the 13q gene at
      theta = 0.10 as responsible for the DLMD phenotype in our families using both
      13q12 markers, if the lod scores of each family were added up. Interestingly, 3
      families were deficient for 50 DAG while one showed a positive pattern for this
      glycoprotein. Therefore, these results suggest: a) the DLMD phenotype is caused
      by more than one recessive gene; b) a gene, not located at 13q, causes deficiency
      of 50 DAG as a primary or secondary defect.

PMID- 8281159
TI  - Identification of two new missense mutations (K58N and R121Q) in the Norrie
      disease (ND) gene in two Spanish families.

PMID- 8281160
TI  - Identification of somatic APC gene mutations in periampullary adenomas in a
      patient with familial adenomatous polyposis (FAP).

PMID- 8281161
TI  - A novel mutation and a polymorphism in the X chromosome located pyruvate
      dehydrogenase E1 alpha gene (PDHA1).

PMID- 8281162
TI  - Novel mutation affecting a splice site in exon 4 of the ornithine carbamoyl
      transferase gene.

PMID- 8281163
TI  - Further evidence that imbalance of WT1 isoforms may be involved in Denys-Drash
      syndrome.

PMID- 8281165
TI  - An extensive de novo deletion removing FMR1 in a patient with mental retardation
      and the fragile X syndrome phenotype.

PMID- 8281164
TI  - A novel mutation of the WT1 gene (a tumor suppressor gene for Wilms' tumor) in a
      patient with Denys-Drash syndrome.

PMID- 8281166
TI  - Four PCR-based polymorphisms in the pseudoautosomal region of the human X and Y
      chromosomes.

PMID- 8281167
TI  - PCR based polymorphisms for D14S242, D14S246, D14S241, D14S243, D14S244 and
      D14S245.

PMID- 8281168
TI  - Dinucleotide repeat polymorphisms at D16S467 and D16S468 and D5S560.

PMID- 8281169
TI  - Dinucleotide repeat polymorphism (D10S608) adjacent to the GLUD1 locus.

PMID- 8281170
TI  - Dinucleotide repeat polymorphism at the D19S386 locus.

PMID- 8281171
TI  - Dinucleotide repeat polymorphism in the human aniridia (PAX6) gene.

PMID- 8281172
TI  - Dinucleotide repeat polymorphism in the INHBA gene.

PMID- 8281173
TI  - Dinucleotide repeat polymorphism in the NEC2 gene.

PMID- 8281174
TI  - Single base polymorphism in the DAG1 gene detected by DGGE and mismatch PCR.

PMID- 8281175
TI  - Tetranucleotide repeat polymorphism at the D8S306 Locus.

PMID- 8281176
TI  - New human DNA polymorphisms submitted to the genome data base.

PMID- 8281177
TI  - Effect of a lateral step-up exercise protocol on quadriceps and lower extremity
      performance.
AB  - Closed kinetic chain exercises have been promoted as more functional and more
      appropriate than open kinetic chain exercises. Limited research exists
      demonstrating the effect of closed kinetic chain exercise on quadriceps and lower
      extremity performance. The purpose of this study was to determine the effect of a
      lateral step-up exercise protocol on isokinetic quadriceps peak torque and the
      following lower extremity activities: 1) leg press, 2) maximal step-up
      repetitions with body weight plus 25%, 3) hop for distance, and 4) 6-m timed hop.
      Twenty subjects participated in a 4-week training period, and 18 subjects served
      as controls. For the experimental group, a repeated measure ANOVA comparing
      pretest and posttest values revealed significant improvements in the leg press (p
      < or = .05), step-ups (p < or = .05), hop for distance (p < or = .05), and hop
      for time (p < or = .05) and no significant increase in isokinetic quadriceps peak
      torque (p > or = .05). Over the course of the training period, weight used for
      the step-up exercise increased (p < or = .05), repetitions decreased (p < or =
      .05), and step-up work did not change (p > or = .05). For the control group, no
      significant change (p > or = .05) occurred in any variable. The inability of the
      isokinetic dynamometer to detect increases in quadriceps performance is important
      because the isokinetic values are frequently used as criteria for return to
      functional activities. We conclude that closed kinetic chain testing and exercise
      provide additional means to assess and rehabilitate the lower extremity.

PMID- 8281178
TI  - Shoulder antagonistic strength ratios during concentric and eccentric muscle
      actions in the scapular plane.
AB  - Reporting agonist/antagonist ratios is frequently more clinically applicable than
      reporting absolute strength values of single muscle groups. The purpose of this
      study was to measure shoulder abduction/adduction and external/internal rotation
      ratios in the functional scapular plane of shoulder movement. Ratios were
      calculated using peak and average torques during concentric and eccentric muscle
      actions, and ratios of healthy males and females were compared. Thirty-six, non
      athletic subjects performed concentric-eccentric cycles at two angular
      velocities. No significant differences were observed in the ratios using peak and
      average torques as criterion measurements. Abduction/adduction ratios using peak
      torques were significantly greater during concentric than eccentric actions.
      External/internal rotation ratios using average torques were significantly
      greater during eccentric than concentric actions. External/internal rotation
      ratios at 180 degrees/sec were significantly greater than those at 90
      degrees/sec. No significant differences were observed between male and female
      subjects. Ratios were higher than previously reported. This was attributed to the
      scapular plane testing position. The clinician should be aware that shoulder
      strength ratios are dependent on position and that the scapular plane may be
      advantageous in some cases for testing and treatment.

PMID- 8281179
TI  - Knee extension and flexion torque as a function of thigh asymmetry.
AB  - Although tape measurement of thigh girth is a common component of a clinical knee
      examination, the implications of thigh girth asymmetry are not well understood.
      The purpose of this study was to examine the relationship between thigh girth
      asymmetry and torque asymmetry for extension and flexion of the knee. Thirty
      subjects with thigh girth asymmetry of at least 2 cm, measured at a site 15 cm
      proximal to the superior pole of the patella, were studied. Subjects were
      measured for girth at 10 sites along each thigh. Knee flexion and extension
      torque production were also tested on a Cybex II isokinetic dynamometer. Girth
      asymmetry was determined by the difference in measurements between the subjects'
      smaller and larger thighs. Percent girth asymmetries varied by site, with the
      greatest average girth asymmetry (asymmetry = 5.94%) at 16 cm proximal to the
      superior patellar pole. Percent peak torque asymmetries were computed from the
      differences between subjects' stronger vs. weaker thighs. Correlations and
      regressions of both extension and flexion torque asymmetries upon girth asymmetry
      sites showed higher associations and less error for more proximal measurements.
      Fair to moderate correlation coefficients (r = .37-.42, p < .05) were
      statistically significant for extension torque asymmetry compared with girth
      asymmetry at sites 12, 14, 16, and 20 cm proximal to the patella and for flexion
      torque asymmetry only at the 14-cm site. Although girth and torque asymmetries
      were found to be somewhat related, percent girth asymmetry provided only a
      limited prediction of percent peak torque asymmetry.

PMID- 8281180
TI  - Postsurgical shoulder strength in the older patient.
AB  - Following surgery, a goal of rehabilitation is to return the surgical extremity
      to its original strength. However, for the older rotator cuff repair patient, we
      are unsure if this is a realistic goal. The purpose of this study was to
      determine the quality of shoulder strength in older males who had undergone
      rotator cuff repair and acromioplasty surgery and to determine if test position
      and test velocity effects for rotation at the shoulder existed. Nine patients
      (mean age = 60.8 years) were tested bilaterally on the Cybex II isokinetic
      dynamometer for two movements (internal/external rotation), two velocities (60
      degrees/sec, 120 degrees/sec), and two positions (neutral, 90 degrees abduction)
      to determine the peak torques for the shoulders. Following a three-way analysis
      of variance (ANOVA) with repeated measures, results indicated that the surgical
      shoulder had torque values approximating the nonsurgical shoulder and that test
      position had no significant effect on the internal or external rotation torques
      produced. As seen with nonshoulder-impaired younger subjects, peak torque
      decreased with increased test velocities. It was concluded that the older rotator
      cuff repair patient may be expected to attain a level of strength in the surgical
      shoulder similar to or exceeding the nonsurgical shoulder and that either test
      position recommended by Cybex for testing of the shoulder rotators was
      acceptable. Clinically, a full functional recovery similar to the nonsurgical
      shoulder should be expected in the older patient with postsurgical rotator cuff
      repair and acromioplasty.

PMID- 8281181
TI  - Nonclinical competencies for physical therapists consulting with business and
      industry.
AB  - Industrial physical therapists (IPTs) are working as external consultants with
      business and industry to provide injury prevention and/or rehabilitation
      services. This consulting presents a very new practice setting for therapists and
      requires specialized nonclinical competencies. The purpose of this study was to
      identify these nonclinical competencies. The research was based on an evaluation
      research model using a stakeholder group. Stakeholders represented five groups:
      1) IPTs, 2) continuing education providers, 3) business and industry employers of
      IPTs, 4) safety/risk managers, and 5) human resource development professionals.
      Thirty-five nonclinical competencies were identified through qualitative analysis
      of in-depth interviews with 17 subject matter experts representing the five
      groups. The competencies addressed marketing, program planning, managing the
      consulting process, training, and understanding organizations. This list of
      nonclinical competencies may serve as a self-assessment tool that IPTs can use to
      help plan their professional development. It may also facilitate planning
      continuing education programs for IPTs.

PMID- 8281182
TI  - Guidelines for functional capacity evaluation of people with medical conditions.
AB  - Functional capacity evaluation is an important and widely available service
      provided by rehabilitation professionals, including many physical therapists. In
      the absence of agreed-upon professional standards, guidelines for practice have
      been developed. These guidelines provide a basis for the development of standards
      of practice which the authors believe should be undertaken on an
      interdisciplinary basis. These guidelines provide a baseline level of care that
      should be maintained by physical therapists and others who provide functional
      capacity evaluation services.

PMID- 8281183
TI  - Three-dimensional joint range of motion measurements from skeletal coordinate
      data.
AB  - Frequently, joint range of motion is reported for a single plane (eg., sagittal,
      coronal, or transverse). However, the arc of joint motion during functional
      activities and many clinical tests encompasses motion in all three planes
      simultaneously. The purposes of this paper are to discuss a method to obtain
      relative joint three-dimensional angular displacement measurements using
      coordinates from skeletal landmarks and provide an analytical example of the
      method using three-dimensional angular displacement of the knee joint as a model.
      In order to calculate the three-dimensional relative motion, an orthogonal
      reference frame for each bone needs to be established. To establish the local
      reference frame, three noncollinear points are used to define unit vectors that
      are mutually perpendicular. Three-dimensional angles can be determined to
      describe the magnitude of the moving body rotation angles about the X, Y, and Z
      axes. These angles indicate the relative motion of body segments for
      abduction/adduction, flexion/extension, and internal/external rotation. The
      technique provides a more vigorous biomechanical understanding of joint motion
      and may have implications for measuring patient progress and evaluating joint
      mobilization treatment. This technique may also serve as a basis for developing
      new evaluation and treatment techniques.

PMID- 8281184
TI  - Quadriceps muscular strength after removal of the central third patellar tendon
      for contralateral anterior cruciate ligament reconstruction surgery: a case
      study.
AB  - Surgical reconstruction of the anterior cruciate ligament (ACL) using a patellar
      tendon autograft is a common orthopaedic procedure. Complications such as
      arthrofibrosis, patellar fracture, significant donor site pain, and quadriceps
      muscle weakness can occur from this procedure. Previous studies have not
      documented the effects of isolated graft procurement without concomitant
      ligamentous reconstruction on the donor extremity. This case study documents the
      clinical outcome results of an individual who underwent a central one-third graft
      harvest from his contralateral uninjured knee for an ACL graft of his injured ACL
      deficient knee. The results indicate that at 4 months following graft
      procurement, the knee extensors were equal to the preoperative isokinetic test
      results of that leg. In addition, the patient exhibited full range of motion and
      no patellofemoral complaints of dysfunction. At 12 months postsurgery, the graft
      donor leg was 5-9% stronger than the preoperative test results. The results of
      this case study suggest that isolated harvesting of a 10-mm central patellar
      tendon free graft may not result in significant quadriceps muscle weakness or
      contribute to donor site pain.

PMID- 8281185
TI  - The anther-specific protein encoded by the Brassica napus and Arabidopsis
      thaliana A6 gene displays similarity to beta-1,3-glucanases.
AB  - An anther-specific Brassica napus cDNA, A6, and two corresponding Arabidopsis
      thaliana genes have been isolated. Sequence analyses of A6 revealed similarity to
      beta-1,3-glucanases. The deduced A6 protein differs from other beta-1,3
      glucanases in the possession of a long C-terminus. Immunoblotting using an
      antibody raised to the A6 protein detects a temporal 60 kDa protein in B. napus
      buds, suggesting that the long C-terminal region is present in the mature
      protein. A6 promoter-GUS and RNase fusions demonstrate that the A6 gene is
      tapetum-specific and temporally expressed with a peak in activity when the plant
      normally expresses callase (a complex of endo- and exo-beta-1,3-glucanase
      activities). The sequence similarity of A6 to other beta-1,3-glucanases, coupled
      with the temporal and spatial expression data, suggests that A6 may be part of
      the callase enzyme complex.

PMID- 8281186
TI  - Identification of photo-inactive phytochrome A in etiolated seedlings and photo
      active phytochrome B in green leaves of the aurea mutant of tomato.
AB  - The contents of spectrophotometrically measurable phytochrome A (PhyA) and
      phytochrome B (PhyB) and the corresponding immunochemically detectable
      apoproteins (PHYA and PHYB) were examined in dark- and light-grown tissues of the
      aurea mutant of tomato and its wild-type (WT). The amount of PHYA in etiolated
      aurea seedlings was found to be about 20% of that in the WT; this PHYA showed no
      photo-reversible changes in absorbance, no downregulation of the level of PHYA in
      light-grown seedlings, and no differential proteolysis of Pr and Pfr species in
      vitro which was seen in the case of the WT. By contrast, the amount of PHYB in
      aurea seedlings was not significantly different from that in WT seedlings.
      Phytochrome isolated from green leaves of the aurea mutant and purified by ion
      exchange chromatography showed a red/far-red reversible spectral change, and its
      elution profile during chromatography was essentially similar to that of PHYB.
      The results indicate that aurea is a mutant that is deficient in photoactive PhyA
      at the etiolated stage, when it contains a spectrally inactive PHYA. However, the
      mutant contains spectrally active PhyB in its green tissue as does the WT.

PMID- 8281187
TI  - An inventory of 1152 expressed sequence tags obtained by partial sequencing of
      cDNAs from Arabidopsis thaliana.
AB  - As part of the goal to generate a detailed transcript map for Arabidopsis
      thaliana, 1152 single run sequences (expressed sequence tags or ESTs) have been
      determined from cDNA clones taken at random in libraries prepared from different
      sources of plant material: developing siliques, etiolated seedlings, flower buds,
      and cultured cells. Eight hundred and ninety-five different genes could be
      identified, 32% of which showed significant similarity to existing sequences in
      Arabidopsis and an array of other organisms. These sequences in combination with
      their positioning on the Arabidopsis genetic map will not only constitute a new
      set of molecular markers for genome analysis in Arabidopsis but also provide a
      direct route for the in vivo analysis of their gene products. The sequences have
      been made available to the public databases.

PMID- 8281188
TI  - The promoter of the Arabidopsis thaliana plastocyanin gene contains a far
      upstream enhancer-like element involved in chloroplast-dependent expression.
AB  - Plastocyanin is part of the photosynthetic electron transport chain in the
      chloroplast and is encoded in the nucleus. Expression of the Arabidopsis thaliana
      plastocyanin gene is organ specific: high mRNA levels are observed in young green
      parts of the plant. Furthermore, expression is dependent on the presence of light
      and functional chloroplasts. When grown in the presence of norflurazon under
      white light conditions, resulting in the photo-oxidative destruction of the
      chloroplast, plastocyanin mRNA levels are strongly reduced. A -1579 to -9
      promoter fragment confers light-regulated and chloroplast-dependent expression to
      the beta-glucuronidase reporter gene in transgenic tobacco plants. This suggests
      that regulation takes place at the level of transcription. A plastocyanin
      promoter deletion series ranging from -1579 to -121 which was also tested in
      tobacco, revealed the presence of a strong positive regulating element (PRE) in
      the -1579 to -705 region. Deletion of this part of the promoter resulted in a
      approximately 100-fold reduction of GUS expression as measured in mature leaves.
      Surprisingly, this enhancer-like element was capable of stimulating transcription
      from a position downstream of its reporter. Moreover, it could also activate a
      truncated CaMV 35S promoter. Deletion of this element coincides with the loss of
      chloroplast-dependency of reporter gene expression, as judged by norflurazon
      treatment of transgenic seedlings. So, the activity of the PRE itself might
      depend on the presence of functional chloroplasts.

PMID- 8281189
TI  - Molecular characterization and expression of alfalfa isoliquiritigenin 2'-O
      methyltransferase, an enzyme specifically involved in the biosynthesis of an
      inducer of Rhizobium meliloti nodulation genes.
AB  - A cDNA clone encoding an O-methyltransferase (OMT) from alfalfa has been
      isolated, which methylates the 2'-hydroxyl of isoliquiritigenin (2',4,4'
      trihydroxychalcone) to form 4,4'-dihydroxy-2'-methoxychalcone, the most potent of
      the nod-gene-inducing flavonoid derivatives released from alfalfa roots. The cDNA
      clone was identified on the basis of N-terminal sequence identity to purified S
      adenosyl-L-methionine:isoliquiritigenin 2'-O-methyltransferase (chalcone OMT) and
      expression of enzymatically active chalcone OMT protein in Escherichia coli. The
      deduced amino acid sequence showed significant similarities to other OMTs.
      Chalcone OMT is encoded by a small gene family in alfalfa and related sequences
      are present in other legumes. The chalcone OMT gene is expressed primarily in
      alfalfa roots; transcript levels were highest during the first 2 weeks of
      development. The OMT transcript was also detected, to a much lesser extent, in
      root nodules. In contrast, chalcone isomerase (CHI), although expressed at high
      levels in roots, was found in all plant organs and had a somewhat different
      developmental expression pattern. Chalcone OMT transcripts were localized
      primarily to epidermal and cortical cells starting 1.5-2.0 mm behind the root
      tip, whereas CHI transcripts were present at approximately equal levels in
      epidermal, cortical and vascular tissues, both at the root tip and throughout the
      root. Chalcone OMT transcripts were elicitor-inducible in alfalfa cell suspension
      cultures, although only low levels of methoxychalcone accumulated. The
      implications of these results for plant-microorganism interactions are discussed.

PMID- 8281190
TI  - Developmental and pathogen-induced expression of three barley genes encoding
      lipid transfer proteins.
AB  - Clones for three barley non-specific lipid transfer proteins (LTP2, LTP3, and
      LTP4; formerly Cw18, Cw20 and Cw21, respectively) which had been previously shown
      to inhibit growth of plant pathogens, were selected and characterized from a cDNA
      library derived from young etiolated leaves. Genes Ltp2 and Ltp4 were located in
      chromosome 3H and gene Ltp3 was assigned to chromosome 7H by Southern blot
      analysis of wheat-barley disomic addition lines, using gene-specific probes (3'
      ends of cDNAs). These assignments were confirmed by the polymerase chain
      reaction, using specific primers. The three genes were expressed in stem, shoot
      apex, leaves and roots (at low levels) throughout development. Genes Ltp3 and
      Ltp4 were expressed at high levels, and Lpt2 at low levels, in the spike (rachis,
      lemma plus palea and grain coats). Neither of the mRNAs was detected in
      endosperm. The proteins were localized by tissue-printing with polyclonal
      antibodies in the outer cell layer of the exposed surfaces of the plant,
      throughout the embryo, and in vascular tissues. Expression levels in leaves were
      moderately increased by 0.34 M NaCl and by 0.1 mM abscisic acid and were not
      affected by cold, drought, salicylate, 2,6-dichloro-isonicotinic acid, ethylene
      or ethephon. Methyl Jasmonate (10 microM) switched off all three genes.
      Inoculation with Av6 or vir6 isolates of the fungal pathogen Erysiphe graminis
      increased the three mRNAs, especially that of LTP4, which reached a maximum nine
      fold increase 12-16 h after infection.

PMID- 8281191
TI  - Differential expression of two related amino acid transporters with differing
      substrate specificity in Arabidopsis thaliana.
AB  - A general amino acid permease cDNA (AAP2) was isolated from Arabidopsis by
      complementation of a yeast mutant defective in citrulline uptake. Direct
      transport measurements in yeast show that the protein mediates uptake of L-[14C]
      citrulline and L-[14C]-proline. Detailed analyses of the substrate specificity by
      competition studies demonstrate that all proteogenic amino acids are recognized
      by the carrier, including those that represent the major transport forms of
      reduced nitrogen in many species, i.e. glutamine, glutamate and asparagine. Thus,
      AAP2 is less selective as compared with AAP1 and transports basic amino acids
      such as histidine as shown by expression in a histidine transport-deficient yeast
      strain. The predicted polypeptide of 53 kDa is highly hydrophobic with 12
      putative membrane-spanning regions and shows significant homologies to the
      Arabidopsis broad specificity permease AAP1, and a limited homology to bacterial
      branched chain amino acid transporters, but not to any other known proteins.
      Alterations in the charged residues as compared with AAP1 in four regions might
      be involved in the difference in selectivity towards basic amino acids. Both
      genes are highly expressed in developing pods indicating a role in supplying the
      developing seeds with reduced nitrogen. AAP2 is selectively expressed in the stem
      and might therefore play a role in xylem-to-phloem transfer of amino acids during
      seed filling. Furthermore in situ hybridization shows that both genes are
      expressed in the vascular system of cotyledons in developing seedlings.

PMID- 8281192
TI  - [The price of progress].

PMID- 8281193
TI  - [How to evaluate an postgraduate program, in the medical field?].

PMID- 8281194
TI  - [Morphofunctional architecture of the testicular veins in adults].
AB  - The correlation between varicocele and male sterility, mentioned by several
      authors, led us to study the disposition of the testicular veins, especially at
      the level of their ending, trying to provide an anatomical description, which may
      contribute with new etiopathogenic information, in order to interpret that
      pathologic entity. The arrangements of the muscular fiber bundles show a
      different disposition in the right and left side, mainly in their distinct
      orientation. The collagen and elastic tissue show an arrangement similar to the
      muscular fibers, in order to improve the blood flow, sometimes in the reno
      testicular and sometimes in the cavo-testicular junction.

PMID- 8281195
TI  - The relationship between the papillary muscles and the anatomicosurgical segments
      of the left ventricle of the human heart.
AB  - The relationship between the blood supply of the papillary muscles of the left
      ventricle of 90 adult human Caucasian hearts and the arteries of the cardiac
      anatomicosurgical segments was studied after arterial injection of Vinyl acetate
      and partial or total corrosion. The anterior papillary muscle belongs in most
      cases to the I SV segment whereas the posterior muscle belongs to the III DV
      segment, the former pertaining to the left coronary a. and the latter to the
      right a.

PMID- 8281196
TI  - [Differences in blood pressure measurement in the first consultations before and
      after implementation of the National Program of Hypertension Control].
AB  - This study was carried out in order to compare differences in blood pressure
      measurements (BPM) before and after the implementation of the program of
      hypertension control in Salvador, Brazil. Data concerning BPM following the
      program were obtained from medical records of all 846 adult patients who were
      seen in a first consultation basis in 5/16/91 in 23 health services. Data for the
      1982 year-before the program--were published in 1984. Both studies had the same
      methodology. In 1991 the BP was measured in 29.1% of the 846 patients. Taking
      into account the same services included in both studies, the frequency of BPM in
      1991 reached 35.9%, 92.0% more than the 18.7% observed in 1982. Lower frequencies
      of BPM were seen in the State health services all showing reduction in the BPM
      frequencies as compared to 1982 data. The two hospitals associated to the
      "Sistema Unico de Saude" had a bad performance. Patients with ill defined
      diseases and those surveyed about previous history of hypertension reached the
      highest frequencies of BPM (85.4 and 83.3% respectively). Strategies in order to
      improve the BPM in the routine medical work as contributor to the reduction of
      morbidity and mortality by the complications of hypertension are suggested.

PMID- 8281197
TI  - [Mortality from uterine cervix cancer in Rio Grande do Sul].
AB  - The mortality from cervical cancer was studied by checking the death rates in Rio
      Grande do Sul (RS) and in its 24 microregions. Each tendency (linear regression),
      in the period from 1970 to 1989, was also investigated. We have also studied the
      relative rates of this kind of cancer, the comparison with the rate in other
      places and the risk factors. The data were obtained at the Office of Health in
      Rio Grande do Sul as well as in the Statistics and Geography Brazilian Institute
      and World Health Organization. The average mortality rates/100,000 women in RS
      (1970-1989) was 3.8, with ascending tendency. Important differences in the death
      rates in the 24 microregions in RS were observed and they ranged from 2.5 to 6.7.
      The cervical cancer was the fourth cause of death in women from RS (mortality by
      cancer), in 1989. Papillomaviruses and smoking were important factors in the
      development of cervical cancer.

PMID- 8281198
TI  - [Cough: an otorhinolaryngologist's view].
AB  - Persistent cough leads individuals to seek for medical assistance. Clinical
      investigation, however, may not reveal any alteration within the clinic's sphere
      of action. Often enough, some professionals treat the symptom as a disease,
      introducing several medicines, unsuccessfully. The author's experience, as an
      otolaryngologist, allows to state that many of these professionals ignore the
      upper aerodigestive tract as a cough-generator site. The present work discusses
      the alterations on the mentioned tract, which may provoke the cough reflex,
      reviewing, initially, the cough mechanism and the localization of the specific
      receptors. Cough is produce by stimulus at the receptor level or far from it. In
      upper and lower parts of the aerodigestive tract secretions may run to several
      directions. Secretion from the paranasal sinus is a frequent cause of cough.
      Acute sinusitis may occur insidiously bringing about the chronification of the
      inflammation with cough being the only great apparent symptom. Nasal and dental
      alterations favor sinusal infection. Signs and symptoms, even if minimum, may be
      detected through an accurate anamnesis. Nasal allergy, laryngitis, post nasal
      dripping and septal deviation may also produce cough. The ORL examination is,
      therefore, imperative, and no radiologic examination can substitute for it. An
      inadequate treatment, particularly of the sinusitis, may bring about a worsening
      and extension of the initial condition.

PMID- 8281199
TI  - [Treatment of growth hormone deficiency patients with authentic recombinant
      growth hormone].
AB  - Eleven growth hormone deficient (GHD) subjects were treated regularly for 3 years
      with an authentic recombinant growth hormone preparation (0.35 to 0.5U/kg/week).
      Growth velocity (GV) increased from a mean o 2.91 +/- 1.58cm/year during the 1st
      year to 8.62 +/- 2.81cm/y in the 2nd and 7.63 +/- 1.84cm/y in the 3th year of
      follow up. During that period height age (delta HA) increased by 4.9 +/- 1 years
      while bone age advanced 4.3 +/- 1.4 year (delta BA) resulting in a delta HA/delta
      BA of 1.1 +/- 0.2. Since the height increment was associated with BA advancement
      the final height within normal range could not be attained. Thus, GHr therapy
      should be instituted before the height deficit would became intense as it
      happened in the majority of our patients. Early diagnosis and therapy of GHD is
      important, when growth retardation is less severe, in order to allow a better
      final height.

PMID- 8281201
TI  - [Compression of esophagus and trachea by aortic arch anomalies in childhood].
AB  - From February 1985 to November 1992, 14 children with aortic arch anomalies and
      tracheal and/or esophageal compression were treated at the Pediatric Surgery
      Division of the Sao Paulo University School of Medicine. There were 3 cases of
      double aortic arch, 3 of right aortic arch with ligamentum arteriosum and 4 of
      aberrant right subclavian artery. Accurate diagnosis was based only on barium
      esophagoradiogram and, eventually, tracheobroncoscopy. The surgical approach was
      made through a left posterolateral thoracotomy that allowed an adequate exposure
      of the malformations. There was no operative mortality. There were 3 late post
      operative deaths, 2 of them caused by chronic pulmonary lesions owing to delayed
      diagnosis. The other child died from complications of a severe tracheomalacia
      which became symptomatic only after the corrective surgery. The diagnosis of the
      aortic arch anomalies should be early suspected in children with undetermined
      respiratory symptoms and can be easily made basically by esophagoradiogram and
      tracheoscopy.

PMID- 8281200
TI  - [Cardiac involvement in systemic lupus erythematosus: anatomo-pathological
      study].
AB  - To study the cardiac involvement in systemic lupus erythematosus, the clinical
      and necroscopy records of 29 patients were analyzed. Of these, 28 were female and
      1 was male with a mean age of 28.6 +/- 10.4 years. The mean duration of the
      disease was 23.8 +/- 20.1 months. Twenty patients had the diagnosis of renal
      failure, 11 of arterial hypertension and 8 of congestive heart failure. No
      valvular or coronary arterial disease was diagnosed in any patient. The most
      frequent cause of death was sepsis, followed by renal failure. Only one patient
      died of causes directly related to heart disease. At necroscopy, 12 patients had
      pericarditis and 10 had cardiomegaly. Nonspecific valvular abnormalities were
      observed in 2 patients, Libman-Sacks' endocarditis in 1 and bacterial
      endocarditis in 2. Cardiovascular abnormalities were absent in only 8 (7.5%)
      patients. It was concluded that although frequent and contributing to mortality
      in some patients, cardiovascular involvement in systemic lupus erythematosus is
      multifactorial and, usually, nonspecific.

PMID- 8281202
TI  - [Lyme disease: cutaneous involvement and treatment of the initial phases].
AB  - Lyme disease is a tick-transmitted infectious disease caused by Borrelia
      burgdorferi. The clinical spectrum includes manifestations in the skin, heart,
      joints and nervous system. In Brazil no case has been reported with laboratorial
      confirmation. We report a suspect case with clinical and laboratorial findings in
      a young woman who developed cutaneous manifestations. She recovered after
      tetracycline treatment. The usual manifestations and the treatment of early stage
      of the illness are discussed.

PMID- 8281203
TI  - [Suppurative thyroiditis with fatal course in diabetics].
AB  - The authors report two case studies of suppurative thyroiditis in type II
      diabetics patients, giving emphasis to the rapid evolution for sepsis, which took
      one of the patients to death. An earlier diagnosis, antibiotictherapy and a large
      surgical drainage are essential to avoid a fatal course in these patients. A
      brief review of suppurative thyroiditis is also presented.

PMID- 8281204
TI  - [Principles of molecular biology and their applications in medicine].

PMID- 8281205
TI  - [A historical view of the laparoscopic surgery role in the treatment of
      inguinocrural hernias].

PMID- 8281206
TI  - [Pulmonary mycetoma treatment in neutropenic patients].

PMID- 8281207
TI  - Getting students involved.

PMID- 8281209
TI  - Historic strike action underway.

PMID- 8281208
TI  - Problems of a duly authorised job.

PMID- 8281210
TI  - Poor preparation on ethics.

PMID- 8281211
TI  - Using ethics at work.

PMID- 8281212
TI  - Priorities for research.

PMID- 8281213
TI  - Legal workload increases.

PMID- 8281214
TI  - AIDS care changing. Interview by Kathy Stodart.

PMID- 8281215
TI  - NZNO AIDS policy.

PMID- 8281216
TI  - Costs of on-call.

PMID- 8281217
TI  - The gift of a daughter.

PMID- 8281218
TI  - Using resources wisely.

PMID- 8281219
TI  - Techniques for the measurement of body composition: a practical guide.
AB  - This paper discusses some of the practical aspects of both reference body
      composition methods (densitometry, isotope dilution methods, in vivo neutron
      activation analysis, dual energy X-ray absorptiometry, computerized tomographic
      scanning and magnetic resonance imaging) and bedsides or field techniques (weight
      and height indices, skinfold thicknesses impedance/resistance, near infra-red
      interactance and 24 hour creatinine excretion). Some techniques measure gross
      composition, in terms of fat and fat-free mass, or the components of fat-free
      tissue, such as water, mineral and protein, while other methods measure the mass
      of individual tissues, organs or body segments. The choice of a specific method
      for a particular study depends on various considerations including accuracy,
      precision, subject acceptability, convenience, cost, radiation exposure, and the
      need for observer training. The relative advantages and disadvantages of each
      method are discussed with these considerations in mind.

PMID- 8281220
TI  - Randomized evaluation of a low fat ad libitum carbohydrate diet for weight
      reduction.
AB  - Restricting dietary fat intake while consuming carbohydrates ad libitum has
      recently been promoted as a weight loss regimen. Sixty subjects (52 females and
      eight males) were randomized to low fat ad libitum carbohydrate (low-fat) or low
      fat with caloric restriction (low-calorie) behaviour modification treatments.
      Forty-nine subjects completed the 16-20 week programme. Subjects in both groups
      reported averaging over five exercise sessions per week during treatment. The low
      calorie group lost significantly more weight (males 11.8 kg, s.d. 6.4; females
      8.2 kg, s.d. 4.2) than the low-fat group (males 8.0 kg, s.d. 1.3; females 3.9 kg,
      s.d. 3.7). Both groups of subjects lost similar amounts of lean body mass. There
      was significantly greater loss of body fat in the low-calorie group. A slight
      reduction in RMR, adjusted for changes in lean body mass, was observed in both
      groups. Fat intake was reduced from 90 to 30 g per day. Subjects in both groups
      reduced their total energy intake with the low-calorie group consuming fewer
      calories per day than the low-fat group. Both groups showed significant and
      equivalent improvements in eating habits based on microanalysis of eating
      diaries. Eating in social situations and emotional eating, however, continued to
      cause adherence problems during treatment for both groups. Follow-up data
      collected 9-12 months after completion of treatment on 65% of the subjects
      completing the study showed no significant difference between the two groups in
      weight losses from baseline (low-fat group 2.6 kg; low-calorie group 5.5 kg).

PMID- 8281221
TI  - Impaired immunity in obesity: suppressed but reversible lymphocyte
      responsiveness.
AB  - Although obese people have been reported to have a higher incidence of infections
      and some types of cancer, the immunocompetence of obese subjects remains poorly
      understood. To investigate whether obesity affects immunity, we studied obese
      subjects (BMI > 30 kg/m2) whose health was uncomplicated by any other disorder,
      including hyperglycemia. We compared mitogen-induced blastogenic response of
      peripheral blood lymphocytes in 34 obese subjects (mean +/- s.e. BMI: 38.4 +/-
      2.0 kg/m2) and 35 non-obese controls (BMI: 21.3 +/- 0.4 kg/m2) who were matched
      for age and sex. The effects of weight reduction were also evaluated in 19 obese
      persons (BMI: 36.4 +/- 1.8 kg/m2) on a very low calorie diet. Mean (+/- s.e.)
      intracellular incorporation of [3H]-thymidine, on stimulation of T lymphocytes
      with either phytohaemagglutinin (PHA) or concanavalin A (Con A), and B
      lymphocytes with pokeweed mitogen, was significantly diminished in obese subjects
      compared to non-obese controls (47552 +/- 6917 vs. 83720 +/- 6252 cpm, P < 0.001;
      30301 +/- 6018 vs. 45942 +/- 3723 cpm, P < 0.05; 13669 +/- 2971 vs. 23735 +/-
      2048 cpm, P < 0.01, respectively). After weight reduction (BMI: 27.8 +/- 1.2
      kg/m2), the mean T lymphocyte responses to PHA and Con A were increased
      significantly vs. baseline (98404 +/- 2444 vs. 50337 +/- 9516 cpm, P < 0.05 and
      69523 +/- 15480 vs. 36695 +/- 8006 cpm, P < 0.05, respectively). Depressed
      blastogenesis of B lymphocytes was also augmented but was not statistically
      significant. The results suggest that obese subjects have underlying immune
      impairment in responsiveness of lymphocytes and that these impairments are
      reversible with adequate weight reduction.

PMID- 8281222
TI  - Obesity, body fat distribution and sex hormones in men.
AB  - An unfavourable body fat distribution may cause metabolic abnormalities including
      diabetes and dyslipidemia. These effects may be mediated by alterations in sex
      hormones. In women the available data suggest that upper body adiposity is
      related to increased androgenicity (especially as indicated by low concentrations
      of sex hormone binding globulin). Few data, however, are available on these
      relationships in men. We therefore examined the association of total
      testosterone, free testosterone, oestradiol, dehydroepiandrosterone sulphate
      (DHEA-SO4) and sex hormone binding globulin (SHBG) to waist-to-hip ratio (WHR)
      and conicity index in 178 men from the San Antonio Heart Study, a population
      based study of diabetes and cardiovascular disease. The conicity index is equal
      to the abdominal circumference divided by 0.109 x the square root of
      (weight/height). The conicity index and WHR were significantly inversely related
      to DHEA-SO4 and free testosterone. SHBG was only weakly associated with body mass
      index (r = -0.18, P < 0.05). After adjustment for age and body mass index, DHEA
      SO4 remained inversely correlated with WHR (r = -0.22, P < 0.01) and conicity
      index (r = -0.31, P < 0.001) and free testosterone remained inversely associated
      with conicity index (r = -0.21, P < 0.01). Thus, in men, the association between
      unfavourable body fat distribution and increased androgenicity is inverse in
      contrast to the situation in women.

PMID- 8281223
TI  - The relationship between behavioural pattern, overall and central adiposity in a
      population of healthy French men.
AB  - The relationship between obesity, both general obesity (BMI) and central obesity
      (measured by the ratio of iliac and thigh circumferences), and a behavioural
      pattern, which includes alcohol consumption, smoking, stress and lack of sporting
      activity, was investigated in 467 middle-aged French working men. BMI and central
      obesity were closely correlated (r = 0.34). Alcohol consumption was positively
      associated with central obesity (P < 0.001) but it did not significantly
      influence BMI. BMI decreased with cigarette smoking (P < 0.001), but central
      obesity only increased significantly after adjustment for BMI (P < 0.05); thus
      for a given BMI, smoking was associated with a greater degree of central
      adiposity. Resting heart rate (considered as a measure of stress) was positively
      associated with both BMI and the iliac-thigh ratio (P < 0.01, P < 0.05), the
      latter association being due to general obesity. Sporting activity and BMI were
      only marginally associated (P < 0.07) but central obesity decreased with activity
      (P < 0.01). Jointly, alcohol consumption, cigarette smoking, the resting heart
      rate and sporting activity explained 8% of the variance in the iliac-thigh ratio;
      after adjustment for BMI these behavioural variables still explained 6% of the
      variance. Central adiposity, which has recently been described as a risk factor
      for coronary heart disease, non-insulin dependent diabetes and hypertension, was
      significantly associated with a potentially modifiable behavioural pattern.

PMID- 8281224
TI  - Morbid obesity: a comparison between a general population and obesity surgery
      patients.
AB  - Characteristics of morbidity obese adults in the general population and morbidly
      obese adults presenting for obesity surgery were compared. Black morbidly obese
      women in the general population were less obese than black women obesity surgery
      patients, showed less emotional distress, and had fewer abnormal eating
      behaviours; age and socio-economic status were similar. A greater proportion of
      morbidly obese surgery patients were white women than would be expected either on
      the basis of the prevalence of morbid obesity in the general population or on
      census data. It was hypothesized that black women and white men avoid obesity
      surgery until they are physically debilitated by their overweight, while white
      women elect for obesity surgery when the emotional distress associated with
      obesity becomes debilitating.

PMID- 8281225
TI  - Self-reported height and weight and prevalence of obesity. Study in a Spanish
      population.
AB  - The objective of this investigation was to evaluate the usefulness of self
      reported measures of height and weight under the hypothesis that they under
      estimate the prevalence of obesity. A cross-sectional study was carried out on a
      random sample of the adult population of the province of Leon, Spain. The study
      involved 572 participants (262 men and 310 women). All participants were
      interviewed and questioned about socio-cultural characteristics plus their weight
      and height. All respondents were later weighted and measured for height using
      standard methods. A Quetelet or body mass index (BMI) > or = 30 kg/m2 was used as
      the index for obesity. Many people were unaware of their weight and/or height.
      Self-reported BMI could not be calculated in 40 men (15%) and 107 women
      participants (35%). This occurrence was more frequent in women than in men (chi 2
      = 3.98; P < 0.05). The prevalence of obesity, based on measured weight and
      height, was 1.8 times that from self-reported values in men and 2.5 times that
      from self-reported values in women. If we consider only the measured values for
      those individuals who supplied self-reported heights and weights, these
      prevalences fall to 1.7 and 1.6 times those from self-reported values
      respectively. In addition, the difference between measured and self-reported
      height increase with age. All these differences are statistically significant. We
      believe that the use of self-reported values of weight and height in
      epidemiological studies should be avoided in an elderly population. These
      measurements could, however, be used on a younger population.

PMID- 8281226
TI  - [HIV and reproduction].

PMID- 8281227
TI  - [Mastodynias and their treatment].

PMID- 8281228
TI  - [Endoscopy of the penis: technique, diagnosis, treatment].

PMID- 8281229
TI  - [Physiology of the pregnant woman and risk factors].
AB  - Physiological adaptations of the pregnant woman involve the circulatory,
      respiratory, digestive, renal, endocrine and metabolic systems. Their precise
      knowledge allows the clinician to verify the quality of the adaptation of the
      pregnant woman and to avoid unnecessary treatment of physiological changes
      misconsidered as pathological changes in reference to prepregnancy standards.

PMID- 8281230
TI  - [Therapeutic management of antiphospholipid antibody syndrome in pregnancy].
AB  - The antiphospholipid syndrome, recently described, associates thromboembolism
      risks, fetal losses and thrombopenia. An obstetrical survey of this syndrome
      implies previous analyses of maternal and fetal risks and leads to treatment
      which may associate low doses of aspirin, heparin, corticoids. This complex
      syndrome offers the best example of materno-fetal medicine usefulness.

PMID- 8281231
TI  - [Risks related to chronic arterial hypertension: strategy before pregnancy].
AB  - .5% to 3% of pregnancies are complicated by chronic hypertension. These
      pregnancies are at increased risk for the development of superimposed pre
      eclampsia, abruptio placentae, and poor perinatal outcome. The risk of
      development of adverse outcomes are not identical for all the patients. Several
      questions must be solved during the pre-pregnancy visit: What is the seriousness
      of the chronic hypertension? Is the chronic hypertension essential or secondary?
      Are there any organic repercussions of chronic hypertension? Why and how organize
      a special survey for such pregnancies? This complete pre-pregnancy cheek up
      permit to identify the high risk patients and to inform them of necessity of
      adjusted monitoring of the future pregnancy.

PMID- 8281232
TI  - [Infectious diseases and risks in pregnancy: precautions to take and contra
      indications].
AB  - Prenatal diagnosis of toxoplasmosis, rubella, CMV, varicella and parvovirus B19
      are reliable by fetal blood sampling and or amniocentesis. Strategy for improving
      the management is discussed taking into account the specific therapy and the
      contraindications.

PMID- 8281233
TI  - [What are the medical limits on the desire for pregnancy in the woman at risk?].
AB  - Quite a few medical situations are as difficult as the ones where the desire of
      procreation and the risks associated to it are in conflict. The practitioner's
      opinion is grounded on his experience, on statistical data, but also on his own
      sensitivity and subjectivity. His role is not to give the patient the medical
      data and to leave her deciding alone. He must involve himself in the process of
      reflexion and decision, recognize and appreciate the depth of the motivations and
      finally respect them. He must remember that the female intuition bears sometimes
      more value than the so called scientific knowledge.

PMID- 8281234
TI  - [The innocuity of stable products derived from human plasma].

PMID- 8281235
TI  - [Vaginal contraception with ovarian steroids].

PMID- 8281236
TI  - [Retrospective evaluation of an intra-uterine insemination program with donor].
AB  - The results of 109 intra-uterine inseminations with cryopreserved prepared donor
      semen (IUId) in stimulated cycles, performed among 42 couples from November 1987
      to June 1991, were analysed. The single IUId was performed 39 +/- 3 hours after
      the injection of human chorionic gonadotrophin. For each IUID 1,25 +/- 1.4 x
      10(6) motile spermatozoa (mean +/- standard deviation) were inseminated. 27
      pregnancies were obtained and the pregnancy rate per cycle was 24.8%. The number
      of motile spermatozoa inseminated was significantly higher in the group of
      pregnant women than in the population without pregnancy (1.64 x 10(6) x 10(6)/IUI
      versus 1.13 x 10(6)/IUI). The sperm count and the number of motile spermatozoa
      inseminated were significantly higher when the semen was prepared on
      discontinuous Percoll gradients than after swim-up in Menezo B2 medium (8.2 x
      10(6)/ml versus 4.3 x 10(6)/ml and 1.7 x 10(6) versus 0.77 x 10(6)). Among the 27
      clinical pregnancies, 3 were twins and 2 were triplets. The ovarian
      hyperstimulation associated with the use of a prepared semen of donor, generate a
      high risk of multiple pregnancies. To improve the results without increasing the
      risk of multiple pregnancies, we propose to inseminate about 1.5 x 10(6) motile
      spermatozoa with a maximum plasma estradiol level of 1 100 pg/ml, on the day of
      hCG injection, associated with 2 preovulatory follicles. This technique may
      augment the rate of pregnancy and represents an appreciable time gain. These
      results must be confirmed by randomized prospective studies.

PMID- 8281237
TI  - [Pregnancy in the elderly woman].

PMID- 8281238
TI  - [Amenorrhea during menopausal hormone replacement therapy with a percutaneous
      estradiol and oral micronized progesterone combination].
AB  - The effects of oral micronized progesterone-administered at a low dose-on the
      endometrium and on bleeding pattern have been evaluated during a multicenter
      study in which 101 patients were involved. For a minimum of 6 months, patients
      who did not wish to have withdrawal bleeding (98) received the association of 17
      beta-percutaneous estradiol (1.5 mg/d) and oral micronized progesterone (100
      mg/d, at bedtime) during 25 days per month (or 21 d/28). The few women (3) who
      wished regular bleeding were given progesterone (300 mg/d) with estradiol (3
      mg/d), from the 16th to the 25th of the month. No hyperplasia was observed among
      the endometrial biopsies performed after 6 months minimum of treatment. 8% of the
      endometria were partially secretory, 4% were sub-atrophic, 23% were mildly active
      with rare mitoses and 61% were quiescent without mitoses. The remaining 4% were
      considered inadequate. Mitotic activity of the glands was minimal in all
      samplings (mean < 0.53/1,000 cells). The average thickness of the mucosa was
      measured by ultrasonography at 3.9 mm, in the cases of insufficient samplings. No
      bleeding (or spotting, or cyclic bleeding) occurred in 73.3% and 80.9% of the
      cycles, in the 3rd and 6th month of therapy. Therefore a low dose of oral Pg (100
      mg/d) combined with E2 during 25 days/month efficiently controls endometrial
      proliferation, while allowing a very weak cyclic activity. This situation makes
      it possible to minimize spottings and to maintain an amenorrhea in the majority
      of patients, thus letting us hoping for an improvement in the observance of this
      simplified therapy.

PMID- 8281239
TI  - [Progestagens and bones].
AB  - Gestagens when administered alone to menopausal women, (19 nortestosterone or
      progesterone derivatives) suppress loss of mineral content. But often a slight
      bone loss is observed, in contrast to the effect of oestrogenotherapy. 19
      norpregnane derivatives seems to protect against bone loss. Progestagen may
      enhance bone formation without decreasing bone resorption. Administered together
      with oestrogens, gestagens have demonstrated either a decrease in biochemical
      estimates of bone loss or a radiologically positive effect. Progestogens alone in
      premenopausal women have various effects. In the case of contraception by
      injectable MPA the bone mass tend to decline as a result of hypoestrogenism. In
      summary gestagens seem to have on bone mass a rather favourable effect, which
      nevertheless is weaker than that of oestrogen.

PMID- 8281240
TI  - [Evaluation of intra-uterine pathology and tubal patency by contrast echography].
AB  - The contrast ultrasonography (CUS) is a new development of the pelvis
      ultrasounds. A contrast medium is injected through the cervix and is screened
      through the uterine cavity, the tubes and the peritoneal cavity. The contrast
      medium creates a new acoustic interface which improve the quality of the
      ultrasound imaging and the ability to diagnose endouterine pathologies. Further,
      tubal patency may be assessed by tracking fluid into the pouch of Douglas. The
      aim of this study was to assess the feasibility, the accuracy and the side
      effects of this technique when compared with the conventional procedures.
      Included were two groups of patients: the group 1 (10 cases) was of patients with
      menometrorrhagia before undergoing an hysteroscopy; the group II (11 cases) was
      of infertile patients before undergoing a laparoscopic tubal patency test. This
      technique, of low cost and without any radiation exposure, seems to be at least
      as accurate as the conventional methods for the intrauterine diagnostics. It is
      less effectiveness for the evaluation of the tubal patency. No side effect
      occurred in this study.

PMID- 8281241
TI  - [Study of different components in spermatic function after failure of in vitro
      fertilization].
AB  - The fertilizing potential of sperm depends on numerous properties which influence
      its functional competence. In order to understand the causes of IVF failure, we
      studied some of these properties-movement characteristics, hyperactivated
      motility, acrosome reaction-for infertile sperm (0% in vitro fertilization) and
      compared to those of fertile sperm (> or = 50% fertilization, control group).
      Movement characteristics, assessed by video-micrographic analysis, are
      significantly different for the 2 groups: infertile sperm register the lowest
      values for motility characteristics and hyperactivation. The addition of
      ionophore A23187 to the medium improves the hyperactivation and the acrosome
      reaction, the values for the latter, however, remain significantly lower compared
      to the control. These results are in favor of a detailed study of motility and
      induced acrosome reaction as complement for the diagnosis of male infertility.

PMID- 8281242
TI  - Clinical pharmacological issues in treating psychiatric disorders of patients
      with mental retardation.
AB  - The following practical issues in psychopharmacotherapy of patients with mental
      retardation (MR) or other developmental disability (DD) are discussed, with some
      theoretical speculations: Persons with MR/DD have high rates of psychiatric
      disorders/symptoms, many of which are drug-responsive and not satisfactorily
      treated with other modalities alone. However, diagnosis is often complicated by
      concurrent multiple disorders (both psychiatric and medical/surgical), masking or
      distortion of symptoms, and communication impairments. Comorbidity and associated
      treatments should be considered in medication choice. Compared to psychiatric
      patients of normal IQ, patients with MR may be more sensitive to side effects and
      toxicity as well as responsive to lower doses, possibly related to less neuronal
      substrate, qualitative brain differences, or developmental stage. Unexpected or
      disappointing drug responses may also be related to such statistical quirks as
      "end-of-curve" phenomena. Ripples, ratcheting, and other ecobehavioral
      considerations influence treatment outcome and drug management. Target symptoms
      and expected drug benefits should be defined in consultation with caregivers as
      well as, when possible, the patient. Because drug responses of patients with MR
      are especially unpredictable, unreliable, sensitive to dose, and fraught with
      side effects, each medication trial might ideally be approached as a single
      subject experiment on a compassionate protocol: quantify the baseline with
      ratings, behavior counts or other objective measures; start low and titrate
      slowly; monitor progress with repeated objective measures.

PMID- 8281244
TI  - Clinical practice guidelines: a vehicle for improving patient care.

PMID- 8281243
TI  - Fluoxetine compared with imipramine in the treatment of inpatient depression. A
      multicenter trial.
AB  - Fluoxetine and imipramine were compared in a six-week, double-blind, randomized
      trial in 118 men and women, ages 18 to 70 years, hospitalized for major
      depressive disorder. Treatment groups were comparable at baseline. Median
      maintenance doses were: fluoxetine, 80 mg/day; imipramine, 200 mg/day. Efficacy
      with fluoxetine and imipramine was comparable: none of the between-treatment
      differences was statistically significant. Mean +/- standard deviation baseline
      HAMD21 total scores and change (last-visit-carried-forward analysis),
      respectively, were fluoxetine, 28.0 +/- 5.3 and -8.5 +/- 9.9; imipramine, 27.0 +/
      5.8 and -11.9 +/- 9.0. Response and remission rates, respectively, were
      fluoxetine, 54.5 and 21.2%; imipramine, 60.0 and 34.3%. Discontinuations for
      adverse events were comparable (fluoxetine, 21.4%; imipramine, 22.6%). Common
      treatment-emergent events with fluoxetine were dry mouth (28.6%), constipation
      (17.9%), and somnolence (17.9%); those with imipramine were dry mouth (58.1%),
      constipation (32.3%), and headache (22.6%). Fluoxetine was as effective as
      imipramine in this population of inpatients.

PMID- 8281245
TI  - Acute pain management: operative or medical procedures and trauma.

PMID- 8281246
TI  - Violence in the health care environment: strategies for prevention.
AB  - As nurses strive to ensure the personal safety and security of themselves and
      their patients, collaborative work is the key. The building of trust and respect
      occurs when multiple disciplines work together to assess, plan, implement, and
      evaluate strategies to protect all persons in the health care environment from
      violent incidents. The most constructive means of prevention include
      participation in task forces, labor-management committees, and agreements
      obtained through collective bargaining. The health care reform movement is
      emphasizing the delivery of high-quality care to all. Nurses know that assuring
      personal security is the most basic step in meeting a person's health care needs.
      Nurses are well qualified to take the lead in violence-prevention efforts so that
      personal security is ensured for patients and health care workers alike.

PMID- 8281247
TI  - Rx for change?

PMID- 8281248
TI  - Ergonomics: designing patient care to fit the nurse.
AB  - It is time for nurses to take an active role in the prevention of disability from
      back disorders. A systematic program with a strong emphasis on ergonomics is
      proposed as an effective approach. Multidisciplinary participation is essential
      for success. Although it is not realistic to hope that by reading this article
      nurses will become experts in ergonomics, it is reasonable to hope that nurses'
      awareness of ergonomic risk factors will be heightened and that this awareness
      will motivate nurses to start requesting and making positive changes.

PMID- 8281249
TI  - Utility of high resolution capillary electrophoresis for monitoring peptide homo-
      and hetero-dimer formation.
AB  - The monomer and disulfide-linked homo-dimer of two different peptides, one with
      an amino-terminal cysteine, the other with a cysteine at the carboxy-terminal,
      are shown to be baseline resolved by capillary electrophoresis in less than 15
      min. Time-course for homo-dimer formation with both peptides, either under mild
      (air) or stronger (hydrogen peroxide oxidizing conditions, was easily monitored.
      Confirmation that the second peak appearing under oxidizing conditions was indeed
      the homo-dimer was obtained with mass spectrometry. The possibility that stronger
      oxidizing conditions led to the production of the sulfonic acid derivative of the
      monomeric peptide, was ruled out through generation of the derivative by
      performic acid oxidation. As expected, the negative charge of the sulfonic acid
      moiety gives the peptide a slower electrophoretic mobility than both the monomer
      and the dimer. Moreover, as would be expected with a sulfonic acid derivative,
      oxidation to the dimeric form was not possible. This was consistent with the
      observation that the homo-dimer peak could be reduced to monomeric form in the
      presence of dithiothreitol. Co-oxidization of the amino- and carboxy-terminal
      peptides led to the expected production of both homo-dimers and the hetero-dimer,
      all of which were resolved.

PMID- 8281250
TI  - Capillary electrophoresis of abnormal hemoglobins associated with alpha
      thalassemias.
AB  - Capillary electrophoresis was evaluated for separation of hemoglobin species
      associated with alpha-thalassemias, and for identification of hemoglobin variants
      commonly found in the same human populations. Separation of hemoglobins was
      achieved using capillary isoelectric focusing with chemical mobilization; visible
      wavelength absorbance detection was used to identify hemoglobins against a
      background of nonheme-containing proteins. This technique could easily
      differentiate hemoglobins Bart's and H (associated with alpha-thalassemias) from
      hemoglobin variants. Analysis of globin chains derived from intact hemoglobins
      was performed by free zone capillary electrophoresis under denaturing conditions.
      This technique was useful for distinguishing Hb Bart's and Hb H, and for
      confirming the identity of hemoglobin variants.

PMID- 8281251
TI  - Effect of detergents on the electrophoretic behaviour of plasma apolipoproteins
      in capillary electrophoresis.
AB  - The influence of various detergents on the capillary electrophoretic behaviour of
      plasma apolipoproteins was studied. Electrophoretic mobility increased in the
      presence of anionic detergents sodium deoxycholate (DOC) and sodium dodecyl
      sulfate (SDS), and decreased in the presence of non-ionic Triton X-100.
      Apolipoproteins from plasma low-density lipoproteins (LDLs) and high-density
      lipoproteins (HDLs) exhibited different affinities for DOC and SDS. Optimal
      separation and reproducibility of HDL and LDL apolipoproteins was obtained using
      high-pH buffers containing SDS. Good resolution of very-low-density lipoprotein
      (VLDL) apolipoproteins was obtained on addition of either SDS or cetyl
      trimethylammonium bromide to the running buffer. For VLDL apolipoproteins the use
      of polyacrylamide coated capillaries yielded better results.

PMID- 8281252
TI  - Evaluation of sodium dodecyl sulfate non-acrylamide, polymer gel-filled capillary
      electrophoresis for molecular size separation of recombinant bovine somatotropin.
AB  - Sodium dodecyl sulfate (SDS) non-acrylamide, polymer gel-filled capillary
      electrophoresis was examined as an alternative to the high-performance size
      exclusion chromatographic (HPSEC) method for the analysis of recombinant bovine
      somatotropin (bovine growth hormone, rbSt). A calibration curve for the molecular
      mass of protein standards (M(r) 14,000 to 97,000) was linear (r2 = 0.998) when
      the molecular mass of the proteins and their peak migration time were plotted on
      a logarithmic (log-log) scale. Relative standard deviation (R.S.D.) of the
      molecular mass determination was approximately 2-3%. A pre-production as well as
      a production lot of the SDS gel-filled capillary columns were examined.
      Performance of both of these columns were equivalent. Peak migration time
      remained relatively constant beyond 140 sample injections. Gradual loss of
      theoretical plates was noted over the course of the assay; however, the peak
      resolution remained adequate for the analysis of rbSt. Peaks corresponding to
      monomer, dimer, trimer, and tetramer of rbSt were base-line resolved by the SDS
      gel-filled capillary electrophoresis. Theoretical plate of the monomer peak was
      approximately 28,000-30,000 per 40 cm column. Both the monomer and the dimer
      recovery studies indicated that the calibration curves are linear (r2 > 0.993)
      and the slopes are not different from one. Amounts of the components in rbSt
      determined by the SDS gel-filled capillary electrophoresis compared well with
      those of the HPSEC method. The results of this study indicated that the SDS non
      acrylamide gel-filled capillary electrophoresis may be a viable alternative to
      the HPSEC method for the molecular size separation and analysis of recombinant
      proteins.

PMID- 8281253
TI  - Characterization and performance of a neutral hydrophilic coating for the
      capillary electrophoretic separation of biopolymers.
AB  - Polyvinylmethylsiloxanediol (50% vinyl) was synthesized and combined with a cross
      linker for static coating onto fused-silica columns. After cross-linking and
      binding to the surface, linear polyacrylamide was grafted to the double bonds of
      the siloxanediol; subsequently, this linear polymer matrix was cross-linked with
      formaldehyde. The grafted neutral polymeric layer provided suppression of
      electroosmotic flow and minimized adsorption. This combination yielded successful
      open tube and polymer network separations of proteins, peptides and DNA
      molecules. Very high efficiencies (ca. 1 x 10(6) plates/m) were achieved for open
      tube protein separations, and hundreds of consecutive runs were performed with
      minimal change in migration times.

PMID- 8281254
TI  - High-performance capillary electrophoresis for the determination of trypsin and
      chymotrypsin inhibitors and their association with trypsin, chymotrypsin and
      monoclonal antibodies.
AB  - High-performance capillary electrophoresis (HPCE) was adapted for the
      determination of Kunitz soybean trypsin inhibitor, Bowman Birk inhibitor from
      soybean and protein-type proteinase inhibitors from pea (Pisum sativum L.). The
      method was developed for the determination and characterization of the
      inhibitors, the enzymes trypsin and chymotrypsin and the monoclonal antibodies
      (mAbs) raised against the inhibitors, and also the inhibitor-enzyme and inhibitor
      mAb association complexes. The results from studies involving the use of various
      types of buffers revealed the advantages of having zwitterions such as
      trimethylammoniumpropyl sulphonate (AccuPure) or taurine included in the buffer.
      The use of capillaries dynamically coated with zwitterions efficiently reduced
      the interactions of the proteins with the silica capillary surface, which was
      important for the analyses for trypsin, chymotrypsin and mAbs and their
      association complexes with the inhibitors. The influence of temperature, voltage,
      pH and buffer type on migration times, resolution, peak areas and number of
      theoretical plates was investigated for the proteins studied. The proposed HPCE
      method is very suitable for studies of proteinase inhibitors compared with
      traditional inhibitor studies, and it gives efficient protein separations with
      the possibility of 245,000 plates/m.

PMID- 8281255
TI  - Characterization by capillary electrophoresis of the surface glycoproteins of
      ovine lentiviruses before and after treatment with glycosidic enzymes.
AB  - Ovine lentiviruses are a group of viruses that infect sheep and goats. These
      viruses contain a surface glycoprotein (SU) that is very similar among the viral
      strains. Sera from infected animals react equally well with SU from each strain.
      Monoclonal antibodies produced to SU can distinguish among some of the viral
      strains. In order to delineate these differences we treated SU from several viral
      strains with the glycosidic enzymes. These enzymes included a mixture of
      exoglycosidases, beta-N-acetyl glucosaminidase, neuraminidase and
      endoglycosidases D, F and H. After these treatments we observed changes in the
      reactivities of the monoclonal antibodies that were directed to SU. In order to
      characterize these changes on the surface epitopes, SU from the different viral
      strains were subjected to free zone capillary electrophoresis (CZE) using an 0.02
      M phosphate buffer at pH 9.0 at a running voltage of 5 kV. Differences were
      readily seen between SU that had not been treated and SU that had been treated
      with the glycosidic enzymes. Each viral strain had a characteristic
      electropherogram. The electropherograms indicated that the heterogeneity of the
      charge on SU was increased after the enzyme treatments. From these results we
      have concluded that the carbohydrate moieties play an important role in
      contributing to the surface charge of SU. This charge affects the nature of its
      surface epitopes and has an impact on its biological function.

PMID- 8281256
TI  - Determination of milk proteins by capillary electrophoresis.
AB  - The determination of milk proteins by capillary zone electrophoresis (CZE) is
      hampered by the adsorption of the solute on the capillary wall. The effects of
      pH, ionic strength of the buffer and polymeric additives were studied in
      combination with a hydrophilically coated capillary. Optimum separations were
      obtained at low pH (2.5-3) in aqueous solutions containing 6 M urea and
      methylhydroxyethylcellulose, resulting in a complete separation of the serum
      proteins and caseins, including some genetic variants. The results were compared
      with those achieved with reversed-phase HPLC. With CZE, theoretical plate numbers
      in the range 300,000-700,000 were obtained. The relative standard deviations for
      migration times were below 0.08% and for peak areas were 2-4%. The separation of
      cow, goat and sheep milk proteins and of heat-damaged casein is reported.

PMID- 8281257
TI  - Analysis of a recombinant granulocyte macrophage colony stimulating factor dosage
      form by capillary electrophoresis, capillary isoelectric focusing and high
      performance liquid chromatography.

PMID- 8281258
TI  - Separation of amino acid-oxazole derivatives of the redox coenzyme
      pyrroloquinoline quinone by capillary zone electrophoresis.
AB  - Condensation products (oxazole derivatives) from the reaction of the coenzyme
      pyrroloquinoline quinone (PQQ) with several alpha-amino acids were successfully
      separated by capillary zone electrophoresis. Addition of a certain organic
      solvent such as dimethyl sulphoxide to the electrolyte solution is essential for
      reproducible and complete separation. The organic modifier appears to prevent the
      oxazole derivatives from absorbing on the capillary wall. Product analysis of the
      condensation reactions of PQQ with amino acids was performed by this method and
      the mechanism is discussed briefly. PQQ-spiked bovine serum was also analysed.
      Unsubstituted type 1 oxazole derivative was predominantly detected. This result
      suggests that most of the PQQ in mammalian fluids, if any, exists as PQQ
      derivatives, probably as a type 1 oxazole derivative.

PMID- 8281259
TI  - Simultaneous determination of the migration coefficient of each base in
      heterogeneous oligo-DNA by gel filled capillary electrophoresis.
AB  - The direct determination of migration coefficients was achieved by analysing the
      migration time of heterogeneous oligo-DNA with a gel filled capillary using the
      Gauss least-squares method for the observation functions, assuming that the
      migration time of oligo-DNA is dependent on its base composition and chain
      length. By using the coefficients obtained, the migration time of oligo-DNA of
      any known sequence that does not have a secondary structure can be estimated with
      an accuracy of less than 0.5-mer of cytidine. In addition, from the deviation of
      the actual migration time from the calculated migration time in certain specially
      designed base sequences, the existence of a secondary structure such as a hairpin
      structure was strongly suggested even in the presence of 7 M urea. From the
      investigation of the effects of secondary structure on migration time, it was
      concluded that this approach will give qualitative information on secondary
      structure, which may be applicable in work such as single strand conformational
      polymorphism (SSCP) analysis or antisense DNA analysis, in which secondary
      structure plays an important role in accelerating or decelerating migration
      times. The results of the analysis also predict the apparent chain length
      reversal from short to long together with a reduction in the actual chain length
      in DNA sequencing using capillary electrophoresis.

PMID- 8281260
TI  - Optical resolution by high-performance capillary electrophoresis. Micellar
      electrokinetic chromatography with sodium N-dodecanoyl-L-glutamate and digitonin.
AB  - Optical resolution by micellar electrokinetic chromatography with sodium N
      dodecanoyl-L-glutamate (SDGlu) and with digitonin-sodium taurodeoxycholate (STDC)
      mixed micelles was investigated. Addition of sodium dodecyl sulphate, urea and
      methanol to SDGlu micellar solutions could give improved peak shapes and
      resolution. With SDGlu, phenylthiohydantoin (PTH) derivatives of five DL-amino
      acids (alpha-aminobutyric acid, methionine, norvaline, tryptophan and norleucine)
      were separated from each other and each pair of enantiomers was optically
      resolved. On the other hand, three PTH-DL-amino acids (norvaline, valine and
      alpha-aminobutyric acid) were also successfully resolved with a digitonin-STDC
      urea solution (pH 2.5).

PMID- 8281261
TI  - Capillary electrophoresis of DNA in uncross-linked polymer solutions.
AB  - We have used dilute and semi-dilute uncross-linked hydroxyethyl cellulose (HEC)
      solutions as separation matrices for capillary electrophoresis of DNA restriction
      fragments. In these experiments, we investigated the effects of HEC molecular
      weight and concentration on resolution, attempting to relate these parameters to
      the polymer entanglement threshold concentration. The entanglement thresholds of
      seven molecular weight fractions of hydroxyethyl cellulose were determined from
      viscosity-concentration data; the entanglement threshold was found to scale as N
      1.2, where N = number of HEC monomers. This finding is not in agreement with
      classical scaling arguments. We present a relationship to predict the observed
      entanglement threshold of HEC in solution as a function of number average
      molecular weight. It was found that excellent separation of phi X174/HaeIII DNA
      restriction fragments (72-1353 base pairs) by capillary electrophoresis in HEC
      solutions can be achieved significantly below the entanglement threshold,
      depending on DNA size and HEC molecular weight. The mechanism of separation in
      these uncross-linked polymer solutions must therefore be reexamined. Our
      experiments show that the entanglement threshold is a useful parameter in
      predicting a range of HEC concentrations which will separate certain DNA
      fragments for a given HEC molecular weight. However, the presence of a fully
      entangled network is not a prerequisite for separation.

PMID- 8281262
TI  - Use of glucomannan for the separation of DNA fragments by capillary
      electrophoresis.
AB  - Glucomannan, a natural polysaccharide extracted from Amorphophallus konjac, was
      employed as a sieving additive for the separation of restriction DNA fragments in
      capillary electrophoresis. A stable solution of entangled glucomannan was
      successfully prepared under mild conditions. The separation capillary filled with
      0.25% glucomannan exhibited excellent resolution and reproducibility on
      separation of DNA fragments over the range of ca. 1400 base pairs. The separation
      was dependent on the size of the fragments, which allowed the determination of
      the size of separated DNAs directly from the migration time. In addition to these
      separation characteristics, glucomannan has practical advantages in its chemical
      stability, non-toxicity and ease of handling. Because the method is applicable to
      the separation and characterization of the DNA fragments generated by digestion
      with restriction enzymes or produced by polymerase chain reactions, it is
      concluded that glucomannan is a good alternative to the conventional sieving
      additives for capillary electrophoresis, such as polyacrylamide and
      hydroxymethylcellulose.

PMID- 8281263
TI  - Separation of DNA fragments by capillary electrophoresis using replaceable linear
      polyacrylamide matrices.
AB  - The use of low percent (1.5-6% T) replaceable linear polyacrylamide (LPA) network
      matrices for rapid separation of double-stranded DNA fragments was explored.
      Separations of fragments ranging from 20 to 23,000 base pairs were readily
      achieved. Typically, 4 x 10(6) theoretical plates/m were obtained in less than 30
      min. Short separation times under 2 min were also possible, using the DNA
      intercalating dye, ethidium bromide, along with high electric fields. The high
      resolving power of linear polyacrylamide was demonstrated in the separation of
      two fragments which differ by a single base pair (123/124 base pairs) using 6% T
      LPA and ethidium bromide intercalation. This LPA composition allowed for the
      possible single base-pair resolution of dsDNA fragments up to 300 base pairs in
      length. Several concentrations of the linear polyacrylamide for different ranges
      of fragment lengths have been employed. In addition, replaceable LPA offers the
      advantage of a fresh separation matrix for each run, thus overcoming column
      stability problems and minimizing needs for sample cleanup. Electro-osmotic flow
      was substantially reduced using stable capillary coatings, which were required
      for obtaining high efficiencies and good reproducibility.

PMID- 8281264
TI  - Effect of urea concentration on the base-specific separation of
      oligodeoxynucleotides in capillary affinity gel electrophoresis.
AB  - Base-specific separations of oligodeoxynucleotides were achieved with high
      resolution by electrophoresis, using a urea-gel capillary, in which poly(9
      vinyladenine) (PVAd) was utilized as an affinity ligand. The migration behaviour
      and the plate number of oligodeoxynucleotides were investigated as a function of
      urea concentration between 2 and 10 M in capillary gel electrophoresis (CGE) as
      well as capillary affinity gel electrophoresis (CAGE). The migration time in CGE
      separation increases as urea concentration increases. An increase in the
      viscosity of the gel buffer medium as well as a change in the conformation of
      oligodeoxynucleotides is found to be a predominant factor for an increase in the
      migration time. The migration time and the plate number of oligothymidylic acids,
      which interact with PVAd in CAGE, is manipulated by differing urea concentration,
      which leads to the change in the dissociation process of a specific hydrogen
      bonding between oligothymidylic acids and PVAd. The migration time of
      oligodeoxyadenylic acids, which do not interact with PVAd in CAGE, increases with
      an increase in urea concentration as in CGE separation. The plate number of
      oligodeoxyadenylic acid was not affected by the urea concentration.

PMID- 8281265
TI  - Nurses at very low risk of contracting HIV at work.

PMID- 8281266
TI  - Nurses' attitudes affect lesbians' health care.

PMID- 8281267
TI  - Whistle blowing: you can survive it!

PMID- 8281268
TI  - Big heroes or little heroes?

PMID- 8281269
TI  - Journey to where? Unemployment--this couldn't happen to me, could it?

PMID- 8281270
TI  - Aged care and pharmaceuticals. Part 6 of health care economics.

PMID- 8281271
TI  - Congenital cataract, microphthalmia and septal heart defect in two generations: a
      new syndrome?
AB  - The association of congenital cataracts, microphthalmia and heart disease is well
      recognized in fetal rubella, but genetic causes are comparatively rare and
      recurrence risks are usually low. We describe a woman with an atrial septal
      defect, bilateral congenital cataracts, unilateral microphthalmia and minor
      dysmorphic features, originally attributed to an unidentified infection in utero,
      whose daughter has a similar constellation of heart, eye and facial
      abnormalities. This may represent a new dominantly inherited syndrome.

PMID- 8281272
TI  - Child with fronto-facio-nasal dysplasia, Hirschsprung's disease and hypospadias.
AB  - A 3-year-old male child with fronto-facio-nasal dysplasia is reported. He also
      has Hirschsprung's disease and hypospadias and it is suggested that this syndrome
      may result from disordered neural crest migration.

PMID- 8281273
TI  - Hunter-McAlpine syndrome: report of a third family.
AB  - A 9-year-old girl with craniosynostosis, facial dysmorphism, mental retardation,
      proportionate short stature and acral abnormalities is described, in whom both
      clinical and radiological features support a diagnosis of Hunter-McAlpine
      syndrome. Her mother is mildly affected, confirming previous evidence that this
      syndrome is dominantly inherited and shows considerable phenotypic variability
      within families.

PMID- 8281274
TI  - Multiple anomalies possibly caused by a human homologue to the mouse
      disorganization (Ds) gene.
AB  - We describe a female infant with a combination of hamartomas and limb reduction
      anomalies, which might be caused by a human gene homologous to the mouse mutant
      disorganization (Ds) gene. The family history suggests a paternal uncle may also
      have been affected.

PMID- 8281275
TI  - Developmental anomalies in monozygous twins resembling the human homologue of the
      mouse mutant disorganization.
AB  - Human monozygous (Mz) twins are described with a pattern of abnormalities similar
      to those reported in heterozygous expression of the mouse mutant disorganisation
      gene (Ds). These include anomalies of the skeletal, gastrointestinal, genito
      urinary and central nervous system. Concordance in Mz twins is suggestive of a
      genetic aetiology and lends further credence to the putative existence of a human
      homologue for Ds.

PMID- 8281276
TI  - Cherubism, optic atrophy and short stature.
AB  - A male child with cherubism, visual impairment due to optic atrophy and short
      stature is described. This association has not been reported previously.

PMID- 8281277
TI  - Oculo-auriculo-vertebral spectrum with vascular ring and other unusual anomalies.
AB  - An infant with the oculo-auriculo-vertebral (OAV) spectrum is described with the
      previously unreported association of rectal agenesis with recto-urethral fistula.
      The patient died at the age of 14 weeks from respiratory obstruction. Autopsy
      revealed the cause of death to be tracheal compression from a pulmonary artery
      sling. Previous reports of vascular rings within the OAV spectrum are reviewed,
      and it is concluded that these malformations are an uncommon, but clinically
      important, complication of the disorder.

PMID- 8281278
TI  - Mild de Lange syndrome--does it exist?
AB  - A pair of mildly retarded, microcephalic twins (probably identical) are reported.
      They were initially diagnosed as having the de Lange syndrome on the basis of the
      synophrys, but, on follow-up, their main intellectual defect was in the area of
      expressive speech. It is suggested that the evidence in the literature for the
      existence of so-called mild de Lange is sparse and that the twins in this report
      might well have a different, possibly unique condition.

PMID- 8281279
TI  - Cornelia de Lange syndrome--photo essay.
AB  - Cornelia de Lange syndrome is a rare developmental malformation syndrome
      characterized by developmental delay, retardation of growth, limb reduction
      abnormalities and dysmorphic facial features. With the exception of one case with
      a de novo translocation (Ireland et al., 1991) there are no consistent
      chromosomal abnormalities or biochemical markers. Diagnosis is therefore
      dependent on the recognition of the distinctive facial features. In this photo
      essay we focus on those features which are most specific to the syndrome and
      highlight possible diagnostic pitfalls.

PMID- 8281280
TI  - Agnathia-holoprosencephaly: a new recessive syndrome?
AB  - The association between agnathia and holoprosencephaly is well documented (Pauli
      et al., 1981). Pauli et al. described two female sibs with agnathia and
      holoprosencephaly who were subsequently shown to carry an unbalanced 46,XX, der
      18,t(6;18)(pter p24.1) karyotype (Pauli et al., 1983; Krassikoff and Sekhon,
      1989). All other cases have been sporadic (Cohen, 1989). We present a recurrence
      of agnathia-holoprosencephaly in an unrelated European couple and postulate that
      this association may represent an autosomal recessive syndrome.

PMID- 8281281
TI  - Autosomal recessive alobar holoprosencephaly with cyclops in three female sibs:
      prenatal ultrasonographic diagnosis at 18th week.
AB  - A couple who were first cousins were referred for genetic counselling because of
      a previous spontaneous abortion and two female stillbirths with cyclopia. In the
      18th week of the mother's fifth pregnancy a holoprosencephalic fetus was
      diagnosed by ultrasonography. The pregnancy was terminated. Postmortem computed
      tomography and pathological examination revealed that the female fetus had alobar
      holoprosencephaly with cyclopia. Chromosomal analysis of the fetus was normal.

PMID- 8281282
TI  - A new ectrodactyly syndrome?
AB  - We report a fetus with hydrops, ectrodactyly, syndactyly, duplication of the
      great toes and several other features. From a review of the literature we suggest
      that this constellation of abnormalities has not previously been reported.

PMID- 8281283
TI  - New syndrome with features overlapping the Baller-Gerold and Roberts syndromes.
AB  - A male fetus is described with multiple congenital abnormalities including
      craniosynostosis and bilateral radial aplasia. There are many similarities to the
      case recently reported by Imaizumi and Kuroki (Am J Med Genet 41: 162-163). These
      cases may represent a new syndrome with overlapping features of the Baller-Gerold
      and Roberts syndromes.

PMID- 8281284
TI  - Campomelic dysplasia without overt campomelia.

PMID- 8281285
TI  - Possible form of Fanconi pancytopenia as a phenocopy of the VACTERL association.

PMID- 8281286
TI  - Odontogenic keratocysts do not occur in Noonan syndrome.

PMID- 8281287
TI  - Anterior cervical hypertrichosis versus hairy throat.

PMID- 8281288
TI  - Oral-facial-digital syndromes, 1992.
AB  - In 1988, there were seven conditions which could be considered distinct oral
      facial-digital syndromes (OFDS). Currently there are at least nine, as well as
      different classification systems in use. This paper provides an update on
      recently described OFDS, and discusses alternative classification systems.

PMID- 8281289
TI  - Interleukin-6 and transforming growth factor-beta 1 mRNAs are induced in rat
      facial nucleus following motoneuron axotomy.
AB  - Transection of the rat facial nerve leads to a rapid activation of both
      astrocytes and microglia around axotomized motoneurons. The factors involved in
      glial activation in vivo are poorly defined but cytokines have been implicated as
      major regulators of glial activity in vitro. In the present study we have
      investigated the expression of cytokine mRNAs in the axotomized facial nucleus
      that might be involved in glial activation. Eight hours after axotomy unilateral
      transection of the facial nerve had already induced a rapid accumulation of
      interleukin (IL)-6-mRNA, with a peak at 24 hours. No IL-6 mRNA was detected on
      the unoperated control side. Transforming growth factor (TGF)-beta 1 mRNA was
      detected at low levels in the normal facial nucleus, increasing to three times
      the normal level 2 days after axotomy. After day 7 TGF-beta 1 mRNA levels
      gradually declined, with a second minor peak 21 days after axotomy. In situ
      hybridization experiments, 4 and 21 days after axotomy, localized TGF-beta 1 mRNA
      to activated microglial cells around regenerating motoneurons, as well as
      probably some astrocytes. Motoneurons did not express TGF-beta 1 mRNA. TGF-beta 3
      was found to be normally expressed in the facial nucleus but was not regulated by
      axotomy. No mRNA for IL-1, tumour necrosis factor-alpha or interferon-gamma was
      found in the regenerating facial nucleus at any point in time.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8281290
TI  - Development of calbindin-D28k immunoreactive neurons in the embryonic chick
      lumbosacral spinal cord.
AB  - The development of immunoreactivity for the calcium-binding protein calbindin
      D28k (CaB) was investigated in the embryonic and hatched chick lumbosacral spinal
      cord. CaB-immunoreactive neurons were revealed in the dorsal and ventral horns as
      well as in the intermediate grey matter from early stages of neuronal
      development. CaB immunoreactivity was first detected in large neurons in the
      presumptive dorsal horn at embryonic day 5, while small neurons in the lateral
      dorsal horn were the last to appear, at embryonic day 10. We have identified and
      traced the morphological maturation of six CaB-immunoreactive cell groups, three
      in the dorsal horn and three in the ventral horn. In the dorsal horn these groups
      were (1) large neurons in the lateral dorsal horn (laminae I and IV), (2) small
      neurons in the lateral dorsal horn (lamina II), and (3) small neurons in the
      medial dorsal horn (lamina III). All three groups were present throughout the
      entire length of the lumbosacral spinal cord and showed persistent CaB
      immunoreactivity. In the ventral horn, CaB-immunoreactive neurons were classified
      into the following three categories: (1) Neurons dorsal to the lateral motor
      column (lamina VII). These neurons were present exclusively in the upper
      lumbosacral segments (LS1-3), and they showed steady CaB immunoreactivity during
      their maturation. (2) Neurons at the dorsomedial aspect of the lateral motor
      column (at the border of laminae VII and IX). This population of neurons was
      characteristic of the lower segments of the lumbosacral cord (LS5-7) and
      presented transient CaB expression. (3) Neurons within the lateral motor column
      (lamina IX). These neurons were dispersed throughout the length of the
      lumbosacral spinal cord. They were three to four times more numerous in the upper
      than in the lower lumbosacral segments, and their numbers declined throughout LS1
      7 as the animal matured. The characteristic features of the development of
      neurons immunoreactive for CaB are discussed and correlated with previous
      neuroanatomical and physiological studies concerning sensory and motor functions
      of the developing chick spinal cord.

PMID- 8281291
TI  - Beta APP gene expression is increased in the rat brain after motor neuron
      axotomy.
AB  - The response of the beta APP gene to neuronal injury was studied in the facial
      and hypoglossal nerve nuclei of the rat after corresponding nerve axotomy.
      Increased levels of beta APP 695, 714, 751 and 770 mRNAs were observed after
      either facial or hypoglossal nerve axotomy in the parent ipsilateral motor
      neurons. The increase was gradual, with maximal values 7 days after axotomy. beta
      APP mRNA expression returned to normal values 60 days after the lesion. Increased
      beta APP immunostaining was also detected in ipsilateral chromatolytic motor
      neurons. No change in beta APP immunoreactivity was observed in oligodendrocytes,
      another cell type expressing beta APP under normal conditions. A rapid increase
      in the expression of the GFAP gene was observed in reactive astrocytes
      surrounding chromatolytic neurons in the ipsilateral facial or hypoglossal
      nuclei. Thus, in contrast with other models of neuronal injury, where only the
      Kunitz protease inhibitor-containing beta APP mRNA isoforms are increased, all
      beta APP mRNAs are increased in the axotomy model. Furthermore, although beta APP
      expression has been shown to be increased in reactive astrocytes following
      neuronal injury, in the present study the increase was essentially found in the
      motor neurons reacting to axotomy.

PMID- 8281292
TI  - Embryonic optic nerve tissue fails to support neurite outgrowth by central and
      peripheral neurons in vitro.
AB  - The failure of axon regeneration in the injured mammalian central nervous system
      has been ascribed, in part, to the inhibitory effects of myelin proteins. To
      investigate the influence of myelination on neurite growth and regeneration by
      both central nervous system and peripheral nervous system neurons, isolated rat
      neonatal retinal ganglion cells and adult and neonatal dorsal root ganglion
      neurons were cultured on cryostat sections of both immature unmyelinated and
      mature fully myelinated adult rat optic nerve. In agreement with earlier studies
      using neonatal peripheral neurons, the adult optic nerve failed to support
      neurite outgrowth from any of the neurons tested. A new finding was that tissue
      sections from unmyelinated optic nerve (aged embryonic days 18 and 20, and
      postnatal days 1-3), also failed to support the growth of neurites from neonatal
      retinal ganglion cells and both neonatal and adult dorsal root ganglion neurons.
      Neonatal retinal ganglion cells also failed to extend neurites on sections of pre
      degenerated sciatic nerve, a tissue shown in our previous work to be a good
      substratum for supporting neurite growth for both neonatal and adult DRG neurons.
      These results suggest that cells in the immature optic nerve either express
      widely acting axon growth inhibitory molecules unrelated to previously described
      myelin proteins, or do not synthesize appropriate axon growth promoting
      molecules. They also reveal that, for axon regeneration, central nervous system
      and peripheral sensory neurons require distinct substratum interactions.

PMID- 8281293
TI  - High external potassium induces an increase in the phosphorylation of the
      cytoskeletal protein MAP2 in rat hippocampal slices.
AB  - Depolarization induced in rat hippocampal slices by a high concentration of
      extracellular K+ leads to an increase in the phosphorylation of microtubule
      associated protein MAP2. The comparison of the major phosphopeptides derived from
      in situ and in vitro phosphorylated MAP2 suggests the implication of calcium
      dependent protein kinases, including calcium/calmodulin-dependent protein kinase
      type II and protein kinase C, in the up-phosphorylation of MAP2. In particular, a
      peptide containing the tubulin-binding domain of the MAP2 molecule may be
      phosphorylated by protein kinase C. As the association of MAP2 with the
      cytoskeleton may be regulated by phosphorylation, we suggest that changes in the
      phosphorylation level of MAP2 might be involved in synaptic remodelling in
      hippocampal neurons.

PMID- 8281294
TI  - Cytokines regulate L-arginine-dependent cyclic GMP production in rat glial cells.
AB  - We have previously demonstrated that primary astrocyte cultures from neonatal rat
      cortex and C6 glioma cells express a calcium-independent nitric oxide synthase
      (NOS) on induction with bacterial endotoxin (lipopolysaccharide, LPS). One
      hypothesis regarding the mechanism of the LPS induction is that it causes release
      of cytokines from these cells which then induce the enzyme directly. Such
      cytokine induction of NOS has been demonstrated in many extraneural cell types. L
      Arginine-dependent increases in cyclic GMP correlate with smaller increases in
      accumulation of nitrite, the major oxidation product of nitric oxide, and hence
      can serve as a more sensitive measure of nitric oxide production. Here we provide
      evidence that interferon-gamma (IFN-gamma), interleukin (IL)-1 beta and tumour
      necrosis factor-alpha induce L-arginine-dependent cyclic GMP synthesis in C6
      cells and that a combination of IFN-gamma and IL-1 beta induce L-arginine
      dependent cyclic GMP synthesis in astrocyte cultures, indicating that these
      cytokines induce NOS. In both cell types the induction by cytokines was less
      sensitive to inhibition by dexamethasone, IL-10 and IL-4 than was induction by
      LPS. These data suggest that cytokines can also induce a NOS in glial cells and
      that the mechanism of this induction may be more direct than that of LPS, since
      it is less sensitive to modulation by immunosuppressors. Due to the close
      associations of astrocytes with neurons and microvasculature, cytokine-induced
      NOS could have potentially important pathophysiological effects in the central
      nervous system.

PMID- 8281295
TI  - Sulphhydryl-modifying reagents alter ototoxin block of muscarinic receptor-linked
      phosphoinositide turnover in the cochlea.
AB  - In the 12-day-old rat cochlea, the synthesis of inositol phosphates (IPs) can be
      activated via M3 cholinoceptors. This stimulation is blocked by ototoxins
      (mercury, ethacrynate, cisplatin, neomycin), drugs with side effects that lead to
      damage of hair cells and strial cells. As these toxic effects can be reversed in
      vivo by thiol molecules, we investigated whether modifications of thiol compounds
      could be involved in ototoxin-induced inhibition of the IP turnover in the
      cochlea. For this purpose, we assessed whether the sulphhydryl-modifying reagents
      N-ethylmaleimide and cadmium modify the carbachol-stimulated formation of IPs in
      the 12-day-old rat cochlea. Both molecules inhibit the carbachol effect on a dose
      dependent way without altering the basal metabolism of IPs. As cadmium may block
      some calcium channels, the effect of verapamil, another calcium channel
      antagonist, was tested. Verapamil (1-50 microM) does not alter carbachol-evoked
      IP formation, suggesting that the inhibitory effect of cadmium is not due to a
      calcium influx block. Binding experiments with the muscarinic ligand
      quinuclidinyl benzylate (QNB) showed that the sulphhydryl-modifying reagents do
      not displace QNB from binding sites. Combining ototoxins and reagents shows that
      N-ethylmaleimide acts synergistically with all ototoxins but ethacrynate while
      cadmium does so only with mercury. Both N-ethylmaleimide and cadmium have
      additive effects with ethacrynate. As a supplement, disulphide bond-modifying
      agents do not alter the carbachol-enhanced metabolism of IPs. These results
      suggest that molecules having thiol-modifying properties inhibit the carbachol
      induced turnover of IPs without acting at the muscarinic sites.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8281296
TI  - Differential regulation of preprotachykinin-A mRNA expression in striatum by
      excitation of hippocampal neurons.
AB  - In this report we have studied the influence of hippocampal neurons on
      neuropeptide mRNA expression in both dorsal and ventral striatum in the rat.
      Intrahippocampal unilateral kainic acid injections were performed in control
      animals and in animals with a unilateral 6-hydroxydopamine-induced dopamine
      deafferentation of the striatum. In situ hybridization combined with quantitative
      image analysis was used to study the expression of preprotachykinin A mRNA
      encoding the neuropeptides substance P and neurokinin A. The 6-hydroxydopamine
      induced lesion caused a decrease of preprotachykinin A mRNA levels in the
      ipsilateral dorsal striatum and in both sides of the ventral striatum. In normal
      rats, the intrahippocampal kainic acid injection caused a twofold increase in
      preprotachykinin A mRNA in the limbic parts of the striatum, which are innervated
      by the hippocampus. No effect of the kainic acid injection was seen in the
      lateral parts of the dorsal striatum, a region which does not appear to be
      innervated by the hippocampus. Animals with a 6-hydroxydopamine lesion showed a
      similar kainic acid-mediated increase in preprotachykinin A mRNA in parts of the
      ventral striatum. In the dopamine-lesioned dorsal striatum and ventral striatum
      the decreased preprotachykinin A mRNA levels were normalized by the
      intrahippocampal kainic acid injection. These results show that kainic acid
      mediated excitation of hippocampal neurons causes a dopamine-independent
      induction of preprotachykinin A mRNA expression in parts of the ventral striatum,
      and reverses the dopamine deafferentation-induced decrease of preprotachykinin A
      mRNA in both dorsal and ventral striatum. Combined, our results suggest that
      hippocampal neurons can regulate preprotachykinin A mRNA expression in both the
      ventral and the dorsal striatum.

PMID- 8281297
TI  - Monocularly induced 2-deoxyglucose patterns in the visual cortex and lateral
      geniculate nucleus of the cat: I. Anaesthetized and paralysed animals.
AB  - Extending previous investigations of the topographic relationship between ocular
      dominance and orientation columns in the cat visual cortex the two systems were
      visualized with transneuronally transported [3H]proline and with activity
      dependent uptake of [14C]2-deoxyglucose, respectively. In addition, we used the 2
      deoxyglucose method for a functional assay of both columnar systems. To this end,
      cats were injected with [3H]proline in the right eye. Two weeks later, they were
      stimulated monocularly through this eye by presenting contours of only a single
      orientation in the left and contours of many different orientations in the right
      visual hemifield while 2-deoxyglucose was injected. The patterns of increased 2
      deoxyglucose uptake and of terminal labelling were analysed in flat-mount
      sections of the visual cortices and in frontal sections of the lateral geniculate
      nuclei. In the lateral geniculate nucleus, regions of increased 2-deoxyglucose
      uptake are in register with the [3H]proline-labelled laminae of the open eye. In
      the visual cortex, the hemispheres stimulated with many different orientations
      showed a rather homogeneous accumulation of 2-deoxyglucose over the entire extent
      and throughout all layers of area 17. The hemispheres stimulated with a single
      orientation displayed columnar patterns of orientation domains essentially
      similar to those obtained with binocular presentation of a single orientation. In
      particular and despite monocular stimulation, regions of increased 2-deoxyglucose
      uptake were neither in register with the [3H]proline-labelled terminals of the
      increased 2-deoxyglucose uptake were neither in register with the [3H]proline
      labelled terminals of the stimulated eye in layer IV nor confined to columns of
      neural tissue above and below these terminals. The maximal horizontal offset
      between the termination sites of thalamic afferents and activated orientation
      columns was in the order of 400 microns. These findings suggest several
      conclusions. (i) In the cat visual cortex, binocular convergence seems to occur
      so early in cortical processing that monocular stimulation with many orientations
      leads to a rather homogeneous activation of cortical tissue. (ii) From the
      termination zones of geniculate afferents activity is apparently distributed
      already within layer IV to the respective orientation columns. (iii) This
      horizontal spread of activity could be assured by target cells with radially
      extending dendrites and/or tangentially oriented fibres.

PMID- 8281298
TI  - Monocularly induced 2-deoxyglucose patterns in the visual cortex and lateral
      geniculate nucleus of the cat: II. Awake animals and strabismic animals.
AB  - In the course of experiments studying the organization of ocular dominance
      columns in the visual cortex of cats, we noticed that--contrary to common belief-
      labelling with 2-deoxyglucose after monocular stimulation failed to induce a
      pattern of ocular dominance columns but resulted in a rather homogenous 2
      deoxyglucose uptake throughout area 17 in anaesthetized and paralysed animals. We
      wondered whether 2-deoxyglucose columns could be obtained in awake animals and/or
      in strabismic animals, which have a more pronounced segregation of ocular
      dominance columns. To this end, we investigated 2-deoxyglucose patterns after
      monocular stimulation in three groups of animals: (i) in awake normally reared
      cats, (ii) in awake strabismic cats and (iii) in anaesthetized and paralysed
      strabismic cats. Additionally, we labelled ocular dominance columns with
      intraocular [3H]proline injections. In all cats, monocular stimulation induced 2
      deoxyglucose patterns that were in precise register with the proline-labelled
      ocular dominance columns in layer IV. Regions of increased 2-deoxyglucose uptake
      extended in a columnar fashion through all cortical layers. In contrast to
      normally reared animals, in strabismic cats, the expression of 2-deoxyglucose
      labelled ocular dominance columns was not abolished by anaesthesia or paralysis.
      However, there was a difference between the 2-deoxyglucose patterns in the awake
      normally reared cats and the strabismic animals. In the former, the patches of 2
      deoxyglucose labelling were smaller and occupied less territory than the
      afferents of the stimulated eye in layer IV. Together with the results of the
      previous study, these data indicate that in awake normally reared and in awake
      and anaesthetized strabismic cats, but not in anaesthetized and paralysed
      normally reared animals, monocular stimulation activates selectively neurons in
      columns that are in register with the termination sites of afferents from the
      stimulated eye. This suggests the existence of a mechanism in normally reared
      animals which restricts cortical activation after monocular stimulation to
      territories that are in register with the afferents from the stimulated eye. This
      mechanism appears to be effective only when the animals are awake and actively
      exploring their environment. This and the fact that the active columns were
      narrower than the terminal fields of the stimulated eye suggest an active
      inhibitory process, perhaps related to mechanisms of selective attention. The
      observation that ocular dominance columns persist in strabismic cats even under
      anaesthesia can be accounted for by the lack of binocular convergence in these
      animals.

PMID- 8281299
TI  - Visually triggered neuronal oscillations in the pigeon: an autocorrelation study
      of tectal activity.
AB  - In this study we describe visually triggered gamma oscillations in the optic
      tectum of awake pigeons. This study was motivated by the potential relevance of
      synchronous oscillatory responses in perceptual binding in a laminated structure
      other than the mammalian neocortex. Tectal responses were recorded as local field
      potential and multiunit activity by differential filtering. The local field
      potential was analysed by computing its autocorrelation function and spectral
      power with a moving window applied to single response sweeps. The temporal
      structure of the spike trains was evaluated by computing averaged
      autocorrelograms. A damped sine wave function was fitted to the autocorrelograms
      in order to quantify the degree of oscillation of both signals. Epochs of
      significant oscillatory activity were observed in the local field potential in
      60% of the trials (n = 39). In all trials, significant oscillations occupied
      approximately 10% of the time the stimulus was present. The oscillatory events in
      both the local field potential and the multiunit activity had frequencies in the
      range of 20-50 Hz. It is important to emphasize the great variability in the
      frequency and in the probability of occurrence of the oscillatory responses from
      trial to trial, which makes the oscillatory behaviour of the tectal activity
      highly non-stationary. The oscillatory activity we describe in the avian tectum
      has characteristics similar to those reported in the mammalian neocortex. These
      findings from a fully awake animal strengthen the universality of oscillations as
      a possible carrier for synchronization of activity in the constitution of
      neuronal assemblies.

PMID- 8281300
TI  - Functional organization of auditory cortex in the mongolian gerbil (Meriones
      unguiculatus). I. Electrophysiological mapping of frequency representation and
      distinction of fields.
AB  - The frequency representation within the auditory cortex of the anaesthetized
      Mongolian gerbil (Meriones unguiculatus) was studied using standard
      microelectrode (essentially multiunit) mapping techniques. A large tonotopically
      organized primary auditory field (AI) was identified. High best frequencies (BFs)
      were represented rostrally and low BFs caudally along roughly dorsoventrally
      oriented isofrequency contours. Additional tonotopic representations were found
      adjacent to AI. Rostral to AI was a smaller field with a complete tonotopic
      gradient reversed with respect to that in AI (mirror image representation) and
      was termed the anterior auditory field (AAF). BFs in the range from 0.1 to 43
      kHz, apparently covering the hearing range of the Mongolian gerbil, were found in
      AI and AAF. Units in these two core fields responded to narrow frequency ranges
      with short latencies. Ventral to the common high-frequency border to AAF and AI,
      a rapid transition to very low BFs suggested the presence of a ventral field (V).
      Caudal to AI two small tonotopically organized fields were identified, a
      dorsoposterior field (DP) and a ventroposterior field (VP). The VP showed a
      tonotopic organization mirror imaged to that of AI, i.e. low frequencies were
      represented rostrally near the caudal border of AI, and high frequencies
      caudally. The DP showed a concentric frequency organization with high BFs located
      in the centre. Units in DP and VP fired less strongly, with considerably longer
      latencies, and responded to a broader range of frequencies than units in AI and
      AAF. Dorsocaudal to AI a dorsal field (D) was identified, harbouring units that
      responded to very broad ranges of frequencies. A tonotopic organization of field
      D could not be discerned. In the border region of AI and D, low-frequency
      responses were similar to those found in parts of AI and AAF, but without a clear
      cut tonotopic organization. This region was termed Ald. The two core fields AI
      and AAF appeared to be located within the koniocortex, while the remaining fields
      lay outside. Our data show that the organization of the gerbil auditory cortex is
      highly elaborate, with parcellation into fields as complex as in cat or primates.

PMID- 8281301
TI  - Functional organization of auditory cortex in the mongolian gerbil (Meriones
      unguiculatus). II. Tonotopic 2-deoxyglucose.
AB  - The tonotopic organization of the auditory cortex in the Mongolian gerbil was
      mapped with 2-deoxyfluoro-D-glucose (2DG) using narrow-band frequency-modulated
      tones of different centre frequency (FM tones) and tones periodically alternating
      between two different frequencies (alternating tones) as stimuli. Continuous tone
      bursts of a constant frequency and repetition rate were used in initial
      experiments. Continuous tones produced 2DG patterns similar to those observed in
      animals that were not specifically stimulated. With tone bursts of constant
      frequency and repetition rate variable patterns were observed, some of which
      could be interpreted only in retrospect in the light of results obtained with FM
      tones and alternating tones. These stimuli, in contrast, produced differential
      metabolic responses which in conjunction with 2DG data from monaural animals and
      electrophysiological data made it possible to distinguish a primary auditory
      field AI with its dorsal region Ald, an anterior auditory field AAF, a ventral
      field V, a dorsoposterior field DP and a ventroposterior field VP, a dorsal field
      D, and in addition an anteroventral field AV. In the largest field (AI) and the
      smaller rostrally adjacent field AAF, frequency-specific dorsoventral bands of
      labelling (isofrequency contours) were mapped quantitatively. Bands shifted as a
      function of frequency relative to each other and to an independent spatial
      reference line in the lateral hippocampus. Spatial analysis of the single bands
      obtained with FM tones, and of the double bands obtained with alternating tones
      in both fields, revealed roughly mirror-imaged tonotopic maps of AI and AAF. In
      AI the progression from low to high frequencies was from caudal to rostral and in
      AAF the gradient was reversed, leading to a common high-frequency border of the
      two fields. In AI, the spatial resolution for frequencies below 16 kHz was in
      similar intervals per octave and higher for frequencies below 1 kHz. AI showed a
      somewhat higher spatial resolution for frequencies (at least below 1 kHz) as well
      as longer isofrequency contours than AAF. The 2-deoxyglucose patterns provided
      average tonotopic maps and topological data on various fields, as well as
      reliable landmarks in the gerbil's auditory cortex.

PMID- 8281302
TI  - The isolated and perfused brain of the guinea-pig in vitro.
AB  - We describe here an isolated and perfused in vitro adult guinea-pig whole brain
      preparation which is an extension of the previously described in vitro brainstem
      cerebellum preparation. Viability was tested by the analysis of trans-synaptic
      responses along the visual pathways following the electrical stimulation of the
      optic nerve or the optic radiations. The evoked field potentials were recorded in
      the dorsal lateral geniculate, the superior colliculus and the visual cortex. The
      distribution of extracellular currents was studied using current source density
      analysis, in order to determine the amplitude, time course and spatial
      organization of the synaptic activity at these sites. The study indicates that
      field potentials were very similar to those described in vivo. These data
      demonstrate the survival of a complex adult sensory system in vitro and suggest
      that this preparation can be used for the analysis of multisynaptic circuits in
      the mammalian brain.

PMID- 8281303
TI  - Spatiotemporal induction of immediate early genes in the rat brain after limbic
      seizures: effects of NMDA receptor antagonist MK-801.
AB  - Fos, jun and krox belong to multigene families coding for transcription factors.
      These cellular immediate early genes (IEGs) are thought to be involved in
      coupling neuronal excitation to changes of target gene expression.
      Immunocytochemistry with specific antisera was used to assess regional levels of
      six IEG-encoded proteins (c-Fos, Fos B, Krox-24, c-Jun, Jun B, Jun D) in the rat
      forebrain after kainic acid-induced limbic seizures. The results demonstrate a
      complex spatial pattern of IEG induction and/or suppression in limbic and non
      limbic structures. The sequence of induction within hippocampal subpopulations
      was identical for all IEGs investigated, following the order dentate gyrus, CA1
      and CA3, and irrespective of different temporal profiles for individual
      transcription factors. Since Fos and Jun proteins act via homo- and heterodimer
      complexes at specific DNA sites, our data imply that the postictal combinatorial
      changes of these dimers allow a sequential and differential regulation of target
      gene expression in specific forebrain regions. Pretreatment with the non
      competitive NMDA receptor antagonist MK-801 did not affect kainate-induced
      expression of IEGs in the limbic system, indicating that IEG induction in these
      regions is mediated by high-affinity kainate and AMPA receptors rather than NMDA
      receptors. In contrast, MK-801 abolished IEG induction in the somatosensory
      cortex and striatum, suggesting that IEG expression in non-limbic neurons occurs
      transsynaptically and is mediated by NMDA receptors.

PMID- 8281304
TI  - Propagation of epileptiform activity during development of amygdala kindling in
      rats: linear and non-linear association between ipsi- and contralateral sites.
AB  - The relationship between ipsi- and contralateral epileptiform
      electroencephalographic (EEG) activity was investigated in rats that were kindled
      daily in the amygdala. Two types of relationships--linear and non-linear
      associations--were studied and used to estimate time delays of EEG activity
      between homotopic amygdalar sites during consecutive tetanizations. The
      progressive development of epileptiform EEG and convulsive behaviour was
      accompanied by an increase in association. Maximal association values of the non
      linear function were significantly higher than linear association values. The
      gradual development of motor seizure severity was correlated with increased non
      linearity. Time delays between the two amygdalae were estimated comparably with
      the linear and non-linear function: 30.0 +/- 3.3 and 24.6 +/- 1.7 ms (ipsilateral
      leading contralateral), respectively. However, in rats displaying exclusively
      bilaterally generalized motor convulsions, maximal values of both functions
      decreased but were still significantly higher than control values of phase
      randomized EEG. Corresponding positive as well as negative interhemispheric time
      delays were recorded during the afterdischarge. These results demonstrated a
      strengthened association between the ipsi- and contralateral amygdala during
      primary epileptogenesis induced by amygdala kindling. In contrast, development of
      a secondary focus in the contralateral homotopic region resulted in a weakened
      interhemispheric association. Secondary bilateral synchrony between the ipsi- and
      contralateral amygdala occurred during the evoked epileptiform EEG activity.

PMID- 8281305
TI  - GABAA receptor function in the early period after transient forebrain ischaemia
      in the rat.
AB  - The purpose of this study was to evaluate the function of the GABAA receptor
      following transient forebrain ischaemia. The GABA-stimulated chloride (36Cl-)
      uptake into synaptoneurosomes was determined as an indicator of GABAA receptor
      function. Synaptoneurosomes were isolated from control rats and rats in which the
      forebrain was made ischaemic by way of the two-vessel occlusion model. Animals
      subjected to ischaemia were killed at the end of the ischaemic insult and at 30
      min or 2 or 5 h of recirculation. The results showed a reduction of 75% in GABA
      mediated 36Cl- uptake in synaptoneurosomes isolated from animals shortly (< 0.5
      h) after the ischaemic episode (P < 0.01). After longer recirculation periods the
      GABA-mediated 36Cl- uptake reached preischaemic control levels. To investigate
      whether alterations in 36Cl- uptake were related to the synaptoneurosomal
      metabolic status, the synaptoneurosomal ATP content was measured. The time course
      of the ATP recovery correlated with the recovery of the GABA-mediated 36Cl-
      uptake (r = 0.7, P < 0.001). To investigate the importance of ATP in GABA
      mediated 36Cl- uptake more directly, synaptoneurosomes isolated from control rats
      were exposed to chemically induced ATP depletion with rotenone, an inhibitor of
      oxidative phosphorylation. This resulted in similar reductions in both ATP level
      and GABA-stimulated 36Cl- uptake as observed after in vivo ischaemia. These
      findings indicate that GABAA receptor function is transiently impaired in the
      early postischaemic period in a way which is closely related to alterations in
      cellular energy metabolism. The relevance of these findings to the development of
      ischaemic cell death is discussed.

PMID- 8281306
TI  - Neuroprotective effect of the kappa-agonist enadoline (CI-977) in rat models of
      focal cerebral ischaemia.
AB  - The neuroprotective efficacy of the kappa-opioid agonist enadoline (CI-977) was
      examined in two acute rat models of focal cerebral ischaemia [non-recovery (4 h)
      and recovery (24 h)]. In the non-recovery model, Sprague-Dawley rats were
      anaesthetized throughout the study period. Focal ischaemia was produced by the
      permanent occlusion of the left middle cerebral artery (MCA). The amount of early
      ischaemic damage was assessed in coronal sections at nine pre-determined
      stereotaxic planes. Enadoline at doses of 0.1, 0.3 and 1.0 mg/kg (n = 8),
      administered s.c. 30 min prior to ischaemia, produced dose-dependent amelioration
      of cortical damage. Importantly, enadoline had no significant effect on any of
      the physiological parameters monitored (blood pressure, blood gases, glucose,
      pH). In the recovery model the left MCA was permanently occluded under isoflurane
      anaesthesia. Animals were allowed to recover and were killed 24 h later. The
      amount of ischaemic brain damage and swelling was assessed histologically. In
      this model pretreatment with enadoline at either 0.1, 0.3, or 1.0 mg/kg s.c. was
      followed by continuous s.c. infusion at 0.017, 0.05 or 0.17 mg/kg/h respectively
      (n = 8-17). Enadoline produced dose-dependent reductions in the volumes of
      infarction and brain swelling; the greatest reductions were seen at 1.0 mg/kg
      plus 0.17 mg/kg/h in both infarction (reduced by 37.4% from controls) and
      swelling (reduced by 47.8%). Therefore the kappa-opioid agonist enadoline affords
      dose-dependent neuroprotection in both the non-recovery and recovery models of
      focal cerebral ischaemia in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281307
TI  - Interaction of the amygdala with the frontal lobe in reward memory.
AB  - Five cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to
      associate visual stimuli with food reward. They learned a series of new two
      choice visual discriminations between coloured patterns displayed on a touch
      sensitive monitor screen; the feedback for correct choice was delivery of food.
      Normal learning in this task is known to be dependent on the amygdala. The
      monkeys received brain lesions which were designed to disconnect the amygdala
      from interaction with other brain structures thought to be involved in this
      memory task. All the monkeys received an amygdalectomy in one hemisphere and
      lesions in the other hemisphere of some of the projection targets of the
      amygdala, namely the ventral striatum, the mediodorsal thalamus and the
      ventromedial prefrontal cortex. The rate of learning new problems was assessed
      before and after each operation. Disconnection of the amygdala from the ventral
      striatum was without effect on learning rate. An earlier study had shown that
      disconnection of the amygdala from either the mediodorsal thalamus or the
      ventromedial prefrontal cortex produced only a mild impairment, significantly
      less severe than that produced by bilateral lesions of any of these three
      structures. The present results show, however, that disconnection of the amygdala
      from both the mediodorsal thalamus and the ventromedial prefrontal cortex in the
      same animal, by crossed unilateral lesions of the amygdala in one hemisphere and
      of both the mediodorsal thalamus and the ventromedial prefrontal cortex in the
      other hemisphere, produces an impairment as severe as that which follows
      bilateral lesions of any of these three structures.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8281308
TI  - Detection of a purine analogue-sensitive kinase in frog sciatic nerves--possible
      involvement in nerve regeneration.
AB  - This study reports the existence of a purine analogue-sensitive protein kinase in
      adult frog sciatic nerves. Cell-free supernatants of homogenized regenerating
      sciatic nerves were found to contain a phosphoprotein (MW 90 kDa, referred to as
      PP90), that was phosphorylated to a much higher degree than in normal, uninjured
      nerves. The spatial and temporal characteristics of PP90 phosphorylation
      suggested a relationship with the injury-induced proliferation of support cells
      of the regenerating nerve, i.e. its appearance and increment over time correlated
      with that of [3H]thymidine incorporation in the nerve. PP90 was phosphorylated
      under conditions that excluded enzyme activities due to Ca2+/calmodulin kinases,
      cyclic nucleotide-dependent kinases or protein kinase C. On the other hand, the
      phosphorylation could be selectively inhibited by the purine analogues adenosine,
      2-aminopurine and 6-thioguanine (6-TG). The latter was the most potent and gave
      complete inhibition at 50 microM. Addition of histone H1 to the cell-free assay
      stimulated the phosphorylation of several proteins in both normal and
      regenerating nerves. The stimulation could be blocked by 6-TG, indicating the
      presence of a purine-sensitive kinase also in uninjured nerves. Separate
      experiments showed that in vitro regeneration of the frog sciatic sensory axons,
      as well as the proliferation of the support cells, was inhibited by 100 microM 6
      TG.

PMID- 8281309
TI  - Functional heterogeneity of hippocampal GABAA receptors.
AB  - gamma-Aminobutyric acid type A (GABAA) receptors were studied in cultured neurons
      taken from rat hippocampus at early postnatal stages. GABA-induced whole-cell
      currents showed a broad range of peak amplitudes and time-courses of
      desensitization. Dose-response curves of rapidly and slowly desensitizing cells
      revealed EC50 values of 8.5 and 37.3 microM GABA, respectively, with the Hill
      coefficient being greater than unity. The main-state conductance of GABAA
      receptor channels was 28-31 pS in all cells. GABA responses of low-affinity cells
      were more strongly affected by benzodiazepine receptor agonists (e.g.
      flunitrazepam, clonazepam) and inverse agonists (e.g. methyl-6,7-dimethoxy-4
      ethyl-beta-carboline-3-carboxylate), as compared to cells exhibiting high
      affinity GABA responses. Currents were also potentiated by zolpidem, but were
      little affected by Ro 15-4513 and Zn2+. These data suggest the presence of
      physiologically and pharmacologically distinct GABAA receptor isoforms in neurons
      of the early postnatal hippocampus, which may subserve different inhibitory
      control mechanisms in this brain region.

PMID- 8281310
TI  - Transection of corticostriatal afferents reduces amphetamine- and apomorphine
      induced striatal Fos expression and turning behaviour in unilaterally 6
      hydroxydopamine-lesioned rats.
AB  - Corticofugal fibres from the prefrontal, prelimbic and anterior sensorimotor
      cortices were transected by a wide coronal knife-cut through the forceps minor.
      The cut was performed on the dopamine-depleted side of unilaterally 6
      hydroxydopamine-lesioned rats, or on either the right or the left side of intact
      rats. Sham-lesioned controls received a superficial cortical cut at the same
      level. Seven days after surgery, apomorphine (0.25 mg/kg s.c.) was administered
      to 6-hydroxydopamine-lesioned animals and D-amphetamine (5 mg/kg i.p.) was
      administered to the non-dopamine-denervated ones. Two hours later, the animals
      were perfusion-fixed for the immunohistochemical detection of the nuclear protein
      Fos. A computerized image analysis technique was used to quantify, bilaterally,
      striatal Fos expression in 11 areas of the striatum. The frontocortical
      transection reduced both apomorphine- and amphetamine-induced Fos expression by
      33-66% within the ipsilateral caudate-putamen. The effect was observed throughout
      the rostral portion of the striatal complex, where the lesioned cortical fibres
      terminate most densely. A separate batch of unilaterally 6-hydroxydopamine
      lesioned rats were used to test the effect of frontocortical transection on
      amphetamine- and apomorphine-induced turning behaviour. Two groups of rats,
      showing similar rates of contralateral turning (7-8 turns/min) in response to
      apomorphine (0.25 mg/kg s.c.), were subjected to either a complete frontocortical
      transection or a sham lesion on the dopamine-denervated side. An additional two
      groups, showing comparable rates of ipsilateral turning (15 turns/min) in
      response to amphetamine (5 mg/kg i.p.), received similar lesions, but now on the
      side ipsilateral to the intact dopaminergic innervation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8281311
TI  - c-fos mRNA is spontaneously induced in the rat brain during the activity period
      of the circadian cycle.
AB  - The basal expression of the proto-oncogene c-fos was studied by Northern blot
      analysis in different regions of the rat brain during 24 h. A striking
      spontaneous oscillation of c-fos mRNA expression was detected in animals kept in
      basal conditions with a 12 h light/12 h dark cycle. In these animals c-fos mRNA
      was just detectable during the rest hours (morning through afternoon), and was
      high during the activity hours (night). The periodicity of this oscillation
      persisted and became free-running when the animals were exposed for 6 consecutive
      days to constant light or darkness. It was thus demonstrated that the fluctuation
      of c-fos expression is circadian and is not created by the light-dark cycle, but
      the latter exerts a synchronizing effect. The oscillation of c-fos mRNA was
      modified by manipulations of the rest-activity cycle. In particular, the
      fluctuation observed in basal conditions was inverted, keeping the animals awake
      during the rest hours (diurnal) and allowing them to sleep in the activity period
      (nocturnal). These data indicated a close relationship between the oscillation of
      c-fos expression and the rest-activity cycle. Finally, electroencephalographic
      (EEG) monitoring was performed under behavioural control for 3 h before the
      animals were killed. These experiments confirmed that, irrespective of the time
      of day, the EEG pattern typical of a state of sleep (including both slow waves
      and paradoxical sleep) was associated with low or undetectable c-fos levels,
      whereas the protracted EEG desynchronization corresponding to wakefulness was
      associated with high c-fos expression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281312
TI  - Muscle afferents innervating skin form somatotopically appropriate connections in
      the adult rat dorsal horn.
AB  - We have studied the somatotopic reorganization in dorsal horn neurons after a
      disruption in the normal spatial arrangement of primary sensory axons in adult
      rats. Muscle afferents were redirected to skin by cutting and cross-anastomosing
      the hindlimb gastrocnemius nerve (GN) and sural nerve (SN). It has previously
      been shown that after 10-12 weeks GN afferents innervate the hairy skin of the
      lateral ankle and calf (previously innervated by SN afferents) and become
      potentially capable of relaying information on the location and intensity of
      stimuli applied to the skin. We determined the receptive field and response
      properties of dorsal horn neurons in the lumbar spinal cord, in regions where the
      lower hindlimb is normally represented. In control animals (with intact or self
      anastomosed sural nerves) very few neurons (< 8%) received any synaptic input
      from the GN as assessed by electrical stimulation of the nerve. In contrast, when
      this nerve innervated skin, many cells responded to GN stimulation, and these
      nearly all had receptive field components in the former SN territory. Moreover,
      in animals with cross-anastomosed nerves, cells without GN inputs all had
      receptive fields outside the former SN skin territory. We have shown that in all
      likelihood GN afferents substituted for SN afferents in subserving the low and
      high threshold receptive fields of dorsal horn neurons. Furthermore, for many
      neurons, receptive fields were formed from inappropriately regrown GN afferents
      and adjacent intact cutaneous afferents (in the tibial or common peroneal
      nerves). Therefore, when GN afferents innervate skin in adult animals, they alter
      their central connectivity in an appropriate manner for their new peripheral
      terminations, so that an orderly somatotopic representation of the hind limb skin
      is maintained. We suggest that this plasticity of dorsal horn somatotopy is
      driven in part by activity-dependent mechanisms.

PMID- 8281313
TI  - Confocal microscopy and computer-assisted image reconstruction of astrocytes in
      the mammalian retina.
AB  - The distribution of astrocytes in the vascularized retina of pigs, rats and cats
      was investigated by confocal microscopy and computer-assisted image processing.
      In whole mounts, immunocytochemical identification was done by staining
      astrocytes for glial fibrillary acidic protein (GFAP), and blood vessels for
      alpha-smooth muscle actin or collagen IV. Double-staining was followed through
      consecutive optical sections and made it possible to precisely align the two
      markers in the inner retina. The resulting computer-assisted image
      reconstructions revealed asymmetric ensheathment of blood vessels by GFAP
      positive fibres. The ultrastructural basis for this asymmetry, as studied by
      electron microscopy, was found to be different in pigs and cats. In the pig,
      astrocytes firmly ensheathed the vessel circumference, but glial filaments were
      much more abundant on the vitreal and lateral than on the scleral side. By
      contrast, in the cat astrocytes were generally confined to regions occupied by
      axonal bundles and constituted only part of the vascular glia limitans, else
      formed by Muller cells. Moreover, our observations unambiguously showed that
      individual astrocytes maintained simultaneous contact with axons and blood
      vessels and lined the vitreous body. The physical links provided by astrocytes
      suggest that they are able to function as central communicating elements between
      ganglion cells, the vasculature and the vitreous body.

PMID- 8281314
TI  - Trophic actions of ciliary neurotrophic factor on murine embryonic carcinoma
      cells.
AB  - Recombinant rat CNTF (ciliary neurotrophic factor) at picomolar concentration
      prevents the death of P19 murine embryonic carcinoma cells that usually follows
      upon withdrawal of serum from the culture medium. For prolonged survival of P19
      cells in serum-free medium, insulin must also be present. In the presence or
      absence of serum, CNTF stimulates the differentiation of P19 cells, inducing the
      formation of neurites and synthesis of neurofilament. The results of
      radioautographic studies with radioiodinated CNTF indicate the presence of high
      affinity binding sites on P19 cells. Equilibration of P19 cells with [125I]CNTF
      followed by incubation with cross-linking reagents reveals evidence for at least
      two putative receptors of approximately 78 and approximately 167 kDa.

PMID- 8281315
TI  - PDGF-BB exerts trophic activity on cultured GABA interneurons from the newborn
      rat cerebellum.
AB  - Platelet-derived growth factor (PDGF) is a well known mitogen for mesenchyme
      derived cells and glial cells. Its presence in neuronal cells of the central
      nervous system has only recently been described. We have shown earlier that
      neurons of newborn rat brains in culture express PDGF beta-receptors and that
      PDGF-BB, a homodimer of PDGF B-chain, increases survival and promotes neurite
      outgrowth of newborn cerebellar cells (Smits et al., Proc. Natl Acad. Sci. USA,
      88, 8159-8163, 1991). In this study, the effects of PDGF on early postnatal rat
      cerebellar cells were further explored. By using chemically defined serum-free
      medium, we have established primary cell cultures of rat cerebella (postnatal day
      4-5) containing 70-80% neuronal cells. During the first 10 days in vitro, no
      difference in total cell number was found between PDGF-BB-treated and untreated
      cultures. After this time period, however, increased survival of the PDGF-BB
      treated cells was found. Within the first 10 days in vitro, the addition of PDGF
      BB to the cultures resulted in a relative increase in survival of interneurons
      expressing glutamic acid decarboxylase (GAD), the GABA biosynthetic enzyme.
      Moreover, addition of PDGF-BB in the untreated cell culture resulted in a rapid
      increase of GAD mRNA. These results show that PDGF-BB acts as a trophic factor on
      GABAergic interneurons of the cerebellum by up-regulating GAD synthesis and
      prolonging the survival of these cells. Furthermore, in situ hybridization
      revealed that there are scattered cells present in the early postnatal cerebellum
      that express PDGF beta-receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281316
TI  - Voltage-dependent currents in microvillar receptor cells of the frog vomeronasal
      organ.
AB  - Vomeronasal receptor cells are differentiated bipolar neurons with a long
      dendrite bearing numerous microvilli. Isolated cells (with a mean dendritic
      length of 65 microns) and cells in mucosal slices were studied using whole-cell
      and Nystatin-perforated patch-clamp recordings. At rest, the membrane potential
      was -61 +/- 13 mV (mean +/- SD; n = 61). Sixty-four per cent of the cells had a
      resting potential in the range of -60 to -86 mV, with almost no spontaneous
      action potential. The input resistance was in the G omega range and overshooting
      repetitive action potentials were elicited by injecting depolarizing current
      pulses in the range of 2-10 pA. Voltage-dependent currents were characterized
      under voltage-clamp conditions. A transient fast inward current activating near 
      45 mV was blocked by tetrodotoxin. In isolated cells, it was half-deactivated at
      a membrane potential near -75 mV. An outward K+ current was blocked by internal
      Cs+ ions or by external tetraethylammonium or Ba2+ ions. A calcium-activated
      voltage-dependent potassium current was blocked by external Cd2+ ions. A voltage
      dependent Ca2+ current was observed in an iso-osmotic BaCl2 solution. Finally, a
      hyperpolarization-activated inward current was recorded. Voltage-dependent
      currents in these microvillar olfactory receptor neurons appear qualitatively
      similar to those already described in ciliated olfactory receptor cells located
      in the principal olfactory epithelium.

PMID- 8281317
TI  - Distribution of gephyrin transcripts in the adult and developing rat brain.
AB  - The peripheral membrane protein gephyrin copurifies with the inhibitory glycine
      receptor of mammalian spinal cord. It binds with high affinity to polymerized
      tubulin and has been implicated in the anchoring of the glycine receptor to
      cytoskeletal elements. Recently, cDNA cloning has identified variants of the
      gephyrin mRNA, which originate from alternative splicing of four exonic regions
      (cassettes 1-4). In this study, the expression patterns of gephyrin splice
      variants were determined in the adult and developing rat brain by in situ
      hybridization with synthetic oligonucleotide probes. Gephyrin transcripts were
      detected throughout the brain and spinal cord, with mRNAs containing cassette 2
      (C2 transcripts) being predominant in adult animals. C3 and C4 transcripts were
      seen in cerebellar granule cells and in the dentate gyrus, whereas a C1 probe did
      not produce detectable hybridization signals. During development, C2 and C3 mRNAs
      were found in most brain regions. Generally, the spatial and temporal
      distribution of gephyrin transcripts is similar to that of the glycine receptor
      beta subunit mRNA reported previously.

PMID- 8281318
TI  - Persistence of axonal transport in isolated axons of the mouse.
AB  - We have examined the hypothesis, for the case of mouse axons, that isolating an
      axon from its cell body will lead to a rapid failure of fast axonal transport as
      anterogradely moving organelles vacate the axon in a proximo-distal direction,
      and retrogradely moving organelles vacate it in the opposite direction. We used
      CD1 and BALB/c mice and the Wallerian degeneration-resistant mutant C57BL/Ola.
      Sciatic nerves were cut high in the thigh; at various times up to 8 days later
      nerves were removed from the animal and individual myelinated axons from the
      segment distal to the cut were examined by video light microscopy to detect rapid
      organelle transport. Bidirectional fast organelle transport did decrease in
      amount with time but not nearly as rapidly as predicted, and anterograde and
      retrograde organelle velocities remained normal through time. In the C57BL/Ola
      mouse some structurally preserved axons contained organelles that transported at
      normal velocities in the anterograde and retrograde directions for as long as 8
      days after axotomy. To test one of the possible origins of transported organelles
      in long-surviving axons we examined organelle transport very close to narrow
      lesions in axons bathed in a medium compatible with intracellular function. No
      organelles crossed the lesion but bidirectional organelle transport took place
      proximal and distal to the lesion; the amounts were compatible with the
      interpretation that approximately 30% of organelles reversed transport direction
      on either side of the lesion. We propose that at least some of the organelles
      that undergo persistent transport in axons isolated from their cell bodies
      shuttle back and forth between the ends of the isolated segment.

PMID- 8281319
TI  - Tracing neuroepithelial cells of the mesencephalic and metencephalic alar plates
      during cerebellar ontogeny in quail-chick chimaeras.
AB  - The quail-chick chimaera system was used to investigate the origin of the various
      neuronal cell types of the cerebellum from the mesencephalic and metencephalic
      brain vesicles at the 11- to 14-somite stage in the avian embryo. We have already
      demonstrated that the cerebellum is derived from both the mesencephalic and
      metencephalic brain vesicles. The mesencephalic contribution to the cerebellum is
      restricted to a mediodorsal territory inserted as a V-shaped area into the
      primitive metencephalic vesicle through complex morphogenetic movements taking
      place from day 2 to day 4 of embryonic development. Here we report that the
      cerebellar presumptive territory extends along the anteroposterior axis, over the
      caudal half of the mesencephalon and the rostral half of the metencephalon. Along
      the dorsoventral axis, the cerebellar anlage is located in the alar plates at the
      exclusion of the roof and basal plates, i.e. lies in the lateral walls of the
      neuroepithelium in the area included between approximately 25 and 120 degrees
      with respect to the sagittal plane. We also report that the neuroepithelium
      corresponding to the cerebellar presumptive territory also yields other brain
      structures (e.g. part of the optic tectum in the mesencephalon). The external
      granular layer (EGL) arises only from the rostral metencephalon, undergoing
      extensive tangential movements which we have analysed in detail: the more ventral
      the position of cells in the metencephalic alar plates the more rostral and
      lateral is their position in the EGL. Finally, we discuss the fact that the
      cerebellar cortex, an integrative structure of the brain, arises from the alar
      plates of the neural tube. This is consistent with the general spatial
      organization of the neural anlage of the vertebrate embryo, in which this part of
      the neuroepithelium is devoted to the production of interneurons, whereas the
      basal plate and the neural folds yield motor structures and primary sensory
      neurons respectively.

PMID- 8281320
TI  - Sprouting and regeneration of lesioned corticospinal tract fibres in the adult
      rat spinal cord.
AB  - We have studied the effects of tissue transplants and antibodies (IN-1) against
      the myelin-associated neurite growth inhibitory proteins on sprouting and
      regeneration of the rat corticospinal tract (CST). Transplantation of embryonic
      spinal cord tissue into bilateral transection lesions of the lower thoracic
      spinal cord in young adult rats resulted in a marked increase of the sprouting of
      the lesioned CST. This sprouting effect was probably elicited by soluble factors
      released from the transplants, and was enhanced by the IN-1 antibodies. The
      retraction of lesioned CST fibres normally observed with prolonged survival times
      was also reduced by the presence of transplants. In spite of these growth
      promoting effects of the transplants, the regenerative elongation of CST sprouts
      into the caudal spinal cord was dependent upon the neutralization of the myelin
      associated inhibitory proteins. In the controls (no antibodies or control
      antibodies) only 27% of the animals showed elongation of CST fibres exceeding the
      sprouting distance of 0.7 mm. These fibres grew to a maximal length of 1.8 mm
      (mean +/- SEM, 1.2 +/- 0.1). In contrast, 60% of the IN-1-treated, transplant
      containing rats showed elongations of > 0.7 mm, and these fibres grew up to 10.1
      mm (4.6 +/- 0.5). Regenerating fibres crossed the lesion site through remaining
      tissue bridges. Neither embryonic spinal cord transplants nor a variety of
      implanted bridge materials could serve as a substrate for the regenerating CST
      axons.

PMID- 8281321
TI  - In vitro enfolding of olfactory neurites by p75 NGF receptor positive ensheathing
      cells from adult rat olfactory bulb.
AB  - Secondary cultures of adult rat olfactory bulb (OB) contained three different
      types of cell: (i) process-bearing cells; (ii) macrophage-like cells and (iii)
      fusiform cells. The immunohistochemical properties of process-bearing cells
      closely corresponded to those described for ensheathing glia in vivo. The most
      distinctive feature of these cells was their immunoreactivity for low affinity
      nerve growth factor receptor (NGFR). Process-bearing cells also shared the
      ultrastructural properties of ensheathing glia in vivo, as well as the ability to
      ensheath olfactory axons. In contrast, macrophage-like cells had the
      immunostaining properties of microglia, and fusiform cells were likely capillary
      endothelial cells. Neurites outgrowing from olfactory epithelium explants, when
      co-cultured with adult OB cells, grew preferentially over NGFR positive cells.
      Olfactory neurites exhibited NGFR immunoreactivity and were enfolded by NGFR
      positive cells. After ensheathment, this immunoreactivity decreased from the
      neurite and disappeared from the glial membrane in contact with the neurite.
      However, NGFR immunoreactivity was maintained in the portion of the glial
      membrane not involved in ensheathing. In summary, ensheathing cells in vitro
      retained both the ultrastructure shown in vivo and the ability to ensheath
      olfactory neurites. The Schwann cell-like properties of ensheathing glia, could
      partially explain the permissibility of adult OB to axonal growth.

PMID- 8281322
TI  - Trophic factors produced by retinal cells increase the survival of retinal
      ganglion cells in vitro.
AB  - The naturally occurring neuron death of normal development has been shown to
      depend on trophic factors produced and released by target cells. It has also been
      shown that the afferent supply and local interactions play a role in the control
      of this degenerative phenomenon. We studied the effect of trophic factors
      produced by intrinsic retinal cells on the survival of retinal ganglion cells in
      vitro. Retinae of newborn hooded rats were retrogradely labelled with horseradish
      peroxidase injected into the superior colliculus to permit the identification of
      retinal ganglion cells in culture. We tested the effect of conditioned media
      either from aggregates or from explants of retinal cells from neonatal rats on
      the survival of ganglion cells in vitro. Our results showed that both conditioned
      media increased the survival of these cells. The trophic activity was dose
      dependent, was maintained after dialysis against a 12 kDa membrane, was abolished
      by heating at 56 degrees C for 30 min, and was not found in conditioned medium
      from cerebral cortical explants. Conditioned medium obtained without fetal calf
      serum presented the same trophic effect. These results suggest that the local
      control of developmental neuron death by intrinsic retinal cells may be mediated
      by neurotrophic factors.

PMID- 8281323
TI  - Carbachol potentiates Q current and activates a calcium-dependent non-specific
      conductance in rat hippocampus in vitro.
AB  - Intracellular recordings were made from CA1 neurons in rat hippocampal slices
      maintained in vitro. When Na+ currents were blocked with tetrodotoxin and K+
      conductances known to be sensitive to suppression by muscarinic agonists were
      blocked by 2 mM Ba2+, CA1 cells were depolarized by carbachol (3-10 microM) with
      an attendant conductance increase, whereas prior to Ba2+ the agonist produced a
      decrease or no change in conductance. Under voltage clamp at approximately -60 mV
      and in the presence of tetrodotoxin and Ba2+, carbachol (3-10 microM) induced a
      variable-latency biphasic inward current of up to 380 pA associated with a
      conductance increase of approximately 50%. The first phase was associated with an
      increase (more than 2-fold) of the Cs(+)-sensitive, hyperpolarization-activated
      cationic current, IQ. Carbachol also accelerated the kinetics of IQ at -100 mV
      with an average 24% reduction in its activation time constant. The second phase
      reflected an additional inward current that was Cs(+)-resistant, displayed little
      apparent voltage sensitivity and had a mean extrapolated reversal potential,
      determined in the presence of external Cs+ (< or = 5 mM), of approximately -20
      mV. In a small proportion of cells the second phase of inward current was
      followed (or overlapped) by an outward current, also associated with a
      conductance increase, which reversed at approximately -70 mV. These carbachol
      actions were prevented by extracellular 300 microM Cd2+ and 2 mM Mn2+, by high
      levels (> 5 mM) of extracellular Mg2+ or Ca2+, and by omission of Ca2+ or
      reduction of extracellular Na+ to 25 mM by substitution of NaCl with Tris or N
      methyl-D-glucamine. Carbachol action was not mimicked by oxotremorine (< or = 60
      microM), but was irreversibly blocked by this drug. Likewise, atropine (100 nM)
      irreversibly and gallamine (10 microM) reversibly antagonized carbachol's action.
      The action of carbachol was blocked shortly after prior exposure of slices to 2-5
      mM caffeine. Chronic or acute incubation of slices with 2 mM Li+ potentiated
      (between 1- and 2-fold) carbachol responses. The data indicate that muscarinic
      activation increases cationic flux by a calcium-dependent potentiation of IQ and
      activation of a non-selective conductance. The probability that inositol
      phospholipid metabolism is involved in triggering these events is discussed.

PMID- 8281324
TI  - Fos immunoreactivity after stimulation or inhibition of muscarinic receptors
      indicates anatomical specificity for cholinergic control of striatal efferent
      neurons and cortical neurons in the rat.
AB  - Cholinergic neurons play a major role in the control of striatal activity via
      muscarinic receptors. The action of acetylcholine also appears to be dependent on
      the striosome-matrix compartmentalization of the striatum. This study was
      designed to find out whether modification of acetylcholine tone activates neurons
      in the striatum and forebrain of the rat. We looked for the appearance of
      immunoreactivity to Fos, a regulatory protein that is thought to convert synaptic
      signals into changes in gene expression. Pharmacological manipulation of
      muscarinic receptors was found to induce specific patterns of Fos
      immunoreactivity in distinct neuronal populations of the forebrain, including the
      striatum. Oxotremorine, a non-selective muscarinic agonist, induced Fos
      immunoreactivity in the striatum with a large predominance in striosomes (mostly
      in enkephalinergic neurons), in layers 4 and 6 of the cortex, and also in the
      piriform cortex and septum. The muscarinic agonist pilocarpine had an identical
      effect in the cortex, but the striosomal prevalence was less clear-cut than that
      observed after oxotremorine. Treatment with dopamine-depleting agents (6
      hydroxydopamine or reserpine) and inhibitors of glutamate and opiate receptor (MK
      801 and naloxone respectively) had no effect on the action of oxotremorine. This
      suggests that the induction of Fos provoked by oxotremorine does not involve
      dopamine, glutamate or opiates. Atropine, a non-specific muscarinic antagonist,
      also induced Fos immunoreactivity in the striatum but with matrix predominance
      (mostly in substance P neurons), as well as in the cingulate cortex, and the
      olfactory tubercle. Scopolamine, a muscarinic antagonist, induced Fos in both
      striosomal and matrix compartments in the striatum.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8281325
TI  - Induction of fictive locomotion by sulphur-containing amino acids in an in vitro
      newborn rat preparation.
AB  - The role of the sulphur-containing amino acids (SAAs) in the initiation of
      fictive locomotion was tested in an isolated spinal cord preparation from newborn
      rats. These substances were bath-applied and the fictive locomotion was recorded
      in the lumbar ventral roots. It emerged from this study that all the compounds
      tested could trigger an organized pattern (alternating left and right bursts of
      activity) with a dose-dependent response. However, specific frequency and
      concentration ranges were observed with each of these SAAs. Moreover, a clear-cut
      difference between D and L isomers in the ability of the SAAs to induce this
      activity was observed; the SAAs of the D-forms were found to be generally more
      potent than those of the L-forms. The effects of the SAAs were found to be
      mediated by both NMDA and non-NMDA receptors, since they were blocked in a dose
      dependent manner by the specific antagonists of these receptors. Moreover, it was
      observed that beta-p-chlorophenylglutamic acid, an uptake inhibitor of
      homocysteic acid (HCA), potentiated the effect of exogenously applied HCA, which
      supports the idea that HCA may act as a transmitter. The sulphuric and non
      sulphuric amino acids were also classified in their order of potency. The most
      potent compound turned out to be D-homocysteine sulphinic acid, while D-cysteine
      sulphinic acid was the least potent. It also emerged that the maximal frequencies
      obtained with SAAs and excitatory amino acids were in the same range, which might
      correspond to the maximal limits of this system.

PMID- 8281326
TI  - Elevated seizure threshold and impaired spatial learning in transgenic mice with
      putrescine overproduction in the brain.
AB  - We have studied the role of putrescine by using transgenic mouse lines
      overexpressing the human ornithine decarboxylase gene in most of their tissues.
      The aberrant expression of the transgene is most strikingly manifested in the
      brain, leading to an increase of up to 20-fold in putrescine content. We report
      that the transgenic mice with grossly elevated putrescine in all brain regions
      analysed (cortex, striatum, hippocampus and cerebellum) showed a significantly
      elevated seizure threshold to chemical and electrical stimuli, and impaired
      performance in spatial learning and memory tests. The view that putrescine may be
      primarily responsible for these changes was supported by the fact that the
      concentrations of the major neurotransmitter amino acids, glutamate and GABA in
      the brain, were not changed in the transgenic animals, and by the finding that a
      further increase in brain putrescine, achieved by inhibition of the catabolism of
      L-ornithine, appeared to provide additional protection against electroshock
      induced seizures. These results suggest that the commonly observed increase in
      ornithine decarboxylase activity and the massive increase in brain putrescine in
      connection with neuron damage is a neuroprotective measure rather than a cause of
      the damage.

PMID- 8281327
TI  - Modifications in IgG subclasses in the course of immunotherapy with grass pollen.
AB  - In this study, we evaluated the evolution of IgG subclasses in the course of
      immunotherapy, and related this to the clinical evolution. We selected 226 adult
      patients with sensitivity to grass pollen alone, undergoing immunotherapy for 0
      26 months. The following results may be highlighted: 1) IgG1 increased with
      immunotherapy and reached its peak at 6 months; 2) IgG2 increased significantly,
      reaching its peak after 24 months of treatment; 3) IgG3, however, did not present
      significant modifications in the course of immunotherapy; and 4) IgG4 was high in
      all patients undergoing immunotherapy compared to patients without
      hyposensitizing treatment, the peak being reached in the group of patients with
      the longest course of immunotherapy. Only IgG4 showed a positive and significant
      (p < 0.05) correlation with the degree of clinical recovery reached with
      immunotherapy.

PMID- 8281328
TI  - The specific binding of beta-adrenergic ligands and morphofunctional properties
      of erythrocytes in bronchial asthma.
AB  - Peripheral blood erythrocytes from patients with bronchial asthma (BA) and
      preasthma (PA) were investigated using the following methods: 1) the
      radiochemical method for determining the specific binding of beta-adrenergic
      ligands; 2) direct erythrocytometry for erythrocyte diameter; and 3) the
      cytochemical method [paraldehyde fuchsin (PAF) reaction] for membrane
      glycoproteins. The specific binding of beta-adrenergic ligands in erythrocytes
      was decreased in BA and PA patients. The number of erythrocytes of small diameter
      (ESD) showed a tendency to increase in patients with atopic BA and extrapulmonary
      allergies, as well as in healthy subjects with a family history of atopy. The
      percent of PAF-negative erythrocytes was found to be considerably increased in
      atopic BA. It is concluded that general disorders of the membrane-receptor system
      are a fundamental cause of reactivity changes in allergy.

PMID- 8281329
TI  - IgE synthesis-enhancing factor: modification of its production in the course of
      long-term immunotherapy.
AB  - The isotype-specific mechanisms involved in IgE synthesis are a sophisticated
      system about which very little is known. Several research groups have
      demonstrated that there is an enhancing factor (EF) in lymphocyte supernatants
      which is related to the regulation of the synthesis of IgE, and the influence
      medium-long-term immunotherapy (IT) exerts on it. Following this line of
      research, we studied the influence of long-term IT (> 3 years) and the presence
      of interleukin-4 (IL-4), not only in the different fractions where EF is
      contained, but also in lymphocyte supernatants after stimulation. Bidirectional
      mixed lymphocyte cultures were performed between lymphocytes from healthy
      controls (n = 62) and allergic patients (n = 98) after different periods of IT.
      The supernatants obtained were submitted to affinity chromatography and the
      second fractions, containing EF, were added to healthy control lymphocytes (n =
      11) in order to test their enhancing effect on IgE synthesis. Modifications in EF
      production were observed, depending on the duration of IT. There were no
      detectable levels of IL-4 either in EF fractions or supernatants from stimulated
      lymphocytes.

PMID- 8281330
TI  - Library fungi at the University of Sao Paulo and their relationship with
      respiratory allergy.
AB  - In this study, we investigated the fungi most frequently found in the air and the
      books of 28 libraries at the University of Sao Paulo, Brazil. In a second phase,
      314 librarians were questioned about the presence of asthmatic or rhinitic
      symptoms, and the relationship with the site of work. Forty-nine percent of them
      reported this type of symptoms and 80% related them to the place of work. In the
      third stage, librarians underwent intracutaneous tests against the 20 fungi most
      frequently isolated in libraries. Eighteen librarians presented positive tests,
      12 of whom reported rhinitis and 6 of whom were asymptomatic. In 19.5% of
      symptomatic patients wheals > 15 mm were observed after 6 h, while 9% of the
      asymptomatic patients presented similar wheals. Fourteen librarians with positive
      tests underwent tests with each of the 20 fungi constituting the pool. The
      airborne fungi isolated in libraries are likely to be found anywhere in the city
      of Sao Paulo, but they are likely to be present in higher concentrations in
      libraries, subsequently producing respiratory allergies.

PMID- 8281331
TI  - Secondary urticaria due to toxocariasis: possibly caused by ingesting raw cattle
      meat?
AB  - Skin affectation in patients infected by Toxocara spp. is rare even in endemic
      regions. We present a case of a patient that consulted us for a urticarial
      process and a personal history of eating rat cattle meat. After several studies,
      the diagnosis of secondary urticaria due to Toxocara spp. infection was made.
      Improvement of the symptoms was observed after treatment with thiabendazole.

PMID- 8281332
TI  - Two cases of toxic epidermal necrolysis caused by delayed hypersensitivity to
      beta-lactam antibiotics.
AB  - The authors describe two cases of toxic epidermal necrolysis (TEN) caused by
      delayed hypersensitivity to semisynthetic penicillins. The first patient
      developed erythema of the lower limbs following an i.m. injection of ampicillin,
      which progressed to TEN as therapy was continued. Fever and eosinophilic
      leukocytosis were also present. In the second case, TEN developed following oral
      amoxicillin therapy, and was preceded by a diffuse, maculopapular eruption. In
      both cases, symptoms resolved with the prompt administration of steroids. Both
      patients underwent allergological testing: prick test and, if results were
      negative, intradermal tests with penicilloyl-polylysine (PPL), minor determinant
      mixture (MDM), penicillin, amoxicillin and ampicillin. Patch testing with
      penicillin, ampicillin and amoxicillin was also performed. Both patients
      developed positive reactions to the intradermal tests after 6 h, and to patch
      tests after 48-72 h (for ampicillin, amoxicillin and penicillin in the first
      case, and for ampicillin and amoxicillin in the second). The lymphocyte
      transformation test (LTT), performed only in the first case, was positive for
      ampicillin. As these cases demonstrate, delayed hypersensitivity should be
      suspected in cases of drug-related TEN. Patch testing is a simple and useful
      allergological test for these types of cases.

PMID- 8281333
TI  - Pharmacological regulation of the immune system.
AB  - Immunomodulators include any agent or substance that has an effect on the host
      immune system. These effects may be stimulatory, suppressive or regulatory. Many
      drugs, chemicals and microbial products have been identified as having specific
      as well as nonimmunostimulating properties. The first agent to be used clinically
      as an immunostimulating drug was Bacillus Calmette-Guerin (BCG). Subsequently,
      other bacterial derivatives, including Corynebacterium parvum and bacterial
      lipopolysaccharides, were found to have stimulatory effects. Most research in
      immunostimulating agents has been done in cancer chemotherapy, where such
      compounds or preparations have been employed to (hopefully) restore
      chemotherapeutic agent-induced immunosuppression, and thus prevent the
      development of community-acquired or nosocomial infections. In contrast to
      immunostimulants, immunoregulators are traditionally defined as being capable of
      decreasing an abnormally elevated immune response, and therefore restore
      defective immune function. However, the differentiation between immunoregulators
      and immunostimulants is not always clearly defined, as the regulatory effects on
      the immune system of any particular drug may be multifaceted. Clearly, future
      research must be directed at defining the specific mechanisms of action of
      potential therapeutic drugs, and in developing improved molecules to ensure
      safety and efficacy in the clinical setting.

PMID- 8281334
TI  - Alternative milk formulas in allergies to proteins in cow's milk.
AB  - A variety of "hypoallergenic" formulas have appeared on the market over the last
      few years for feeding lactating infants prone to a high atopic risk of allergy to
      cow's milk. These formulas consist of soya preparations, hydrolyzed proteins and
      so-called basic formulas. This paper describes the main characteristics of such
      formulas, with particular emphasis on their tolerance, indications, related
      immunological aspects and antigenic capabilities. Notifications of anaphylactoid
      reactions with hydrolyzed proteins and the possibility of interactions with the
      IgE antibodies in cow's milk indicate such formulas in cases of non-IgE-mediated
      intolerance. Although soya preparations may be allergenic, they do not present
      interactions with the proteins in cow's milk; thus, they are particularly
      indicated in children with protein allergy to cow's milk with specific IgE
      antibodies.

PMID- 8281335
TI  - Systemic anaphylaxis following parenteral orgotein administration.
AB  - We present a patient displaying a systemic anaphylactic reaction after local
      infiltration of orgotein. An IgE-mediated mechanism was demonstrated with skin
      tests and specific IgE measurement. It is concluded that orgotein can rarely
      cause IgE-mediated anaphylaxis.

PMID- 8281336
TI  - Sensitivity to aspirin: a new serological diagnostic method.
AB  - Certain adverse reactions to aspirin (ASA), nonsteroidal anti-inflammatory drugs
      (NSAIDs) and pyrazolone derivatives resemble IgE-mediated hypersensitivity.
      However, convincing evidence of antigen-antibody interactions or inhibition of
      the cyclooxygenase pathway of arachidonic acid metabolism, stimulating the
      production of leukotrienes (LTs) and decreasing the production of prostaglandins
      (PGs), has not been presented. In this study, two types of specific IgE
      antibodies have been found in six serum samples from eight ASA-sensitive patients
      with salicyloyl and O-methylsalicyloyl disks using the Radio Allergo Sorbent Test
      (RAST), whereas no positive result could be found with acetylsalicyloyl disks.
      Further investigation on the specificity of these IgE antibodies and the chemical
      structure of their epitopes were performed by cross-inhibition studies. The
      results are in favor of an IgE-dependent mechanism involved in ASA sensitivity,
      and suggest that determination of specific IgE antibodies would be a safe
      diagnostic method for ASA sensitivity in vitro.

PMID- 8281337
TI  - IgE synthesis suppressor factor: modifications in the course of long-term
      immunotherapy.
AB  - Many authors have described an increase in total serum IgE values during the
      first few months of immunotherapy (IT), followed by a subsequent decrease. In
      previous studies in patients undergoing medium-term IT, we detected an IgE
      synthesis suppressor factor (SF), which was modified during the course of IT. In
      this study, we investigated the influence of long-term IT on the production of SF
      and the lymphocyte response to its stimulus. Mixed bidirectional cultures of
      lymphocytes isolated from healthy individuals (n = 62) and allergic patients (n =
      98) were carried out after different periods of IT. The resulting supernatants
      were subjected to affinity chromatography, from which two fractions were
      obtained: the first one, likely to contain SF, was added to lymphocyte cultures
      from 13 allergic patients undergoing no IT (LyG1) and 6 allergic patients with >
      3 years of IT (LyG5), in order to assess its inhibitory effect on IgE synthesis.
      We found that patients undergoing IT for > 3 years presented a significant
      increase in SF production and an important lymphocyte response to exogenous SF
      from most of the groups studied, but little response to their own SF. These
      results could be ascribed to an alteration in the quantity and/or structure of
      the lymphocyte receptors likely to be sensitive to these factors induced by IT.

PMID- 8281338
TI  - Defective mononuclear phagocyte function in systemic lupus erythematosus:
      relationship of FcRII (CD32) with intermediate cytoskeletal filaments.
AB  - To investigate the mechanisms of impaired Fc receptor-mediated mononuclear
      phagocyte system (MPS) clearance in systemic lupus erythematosus (SLE), we have
      examined FcRII (CD32) and vimentin function in 25 patients with SLE and 36
      healthy adults. In SLE, FcR-mediated phagocytosis of IgG-sensitized bovine
      erythrocytes was decreased (5.9 +/- 2.47 vs. 8.3 +/- 3.59 erythrocytes
      phagocytosed/monocyte/h; p < 0.05), and CD32 and vimentin expression was within
      the normal range; however, the percentage of simultaneously CD32+ and vimentin+
      cells was increased (30 +/- 12 vs. 20 +/- 13; p < 0.05). Circulating immune
      complexes (CIC) were positive in 11 SLE patients, and levels were positively
      correlated with proteinuria (r = 0.53; p < 0.05) and disease activity (r = 0.40;
      p < 0.05). The mobility of membrane molecules, measured as the percentage of
      patients that showed patching and/or capping of CD32, was increased compared with
      controls, but not significantly (p < 0.1). At the same time, redistribution of
      vimentin filaments was observed. In conclusion, our data seem to support the
      possibility of a functional and/or structural alteration in the relationship
      between Fc receptors and intermediate cytoskeletal filaments as a causative
      factor in the deficient internalization of ligands bound to Fc receptors in
      monocytes of SLE patients.

PMID- 8281339
TI  - Anaphylaxis inhibitory factor: clinical evaluation in pediatric patients.
AB  - A factor similar to that reported in mouse, capable of inhibiting the passive
      cutaneous anaphylactic reaction (PCA), has been demonstrated in human sera. The
      present study reports the laboratory and clinical evaluation of this factor in
      pediatric patients. A low percentage of the allergic patients (7.7%) showed the
      inhibitory factor and a positive skin test, while 70% of the nonallergic patients
      showed the inhibitory factor and a negative skin test. The absence of this factor
      showed a significant relationship with the presence of allergy (p < 0.001) and
      with a positive skin test (p < 0.01), although no relationship was observed with
      total plasma IgE levels (p > 0.05). Thus, it is concluded that PCA inhibitory
      factor modifies the expression of IgE without affecting its synthesis. The
      absence of this factor allows the expression of IgE in allergic patients with
      positive skin tests. The clinical implication demonstrated indicates that this
      may be a useful tool in the study of allergic patients.

PMID- 8281340
TI  - Effect of age and helminthic infection on IgE levels in slum children.
AB  - Helminthic infections can cause an IL-4-dependent polyclonal synthesis of IgE,
      which is the major cause of the elevated serum levels of this immunoglobulin in
      tropical populations. In the present study, we measured the IgE levels in the
      serum of children of different ages in slum areas of Caracas, Venezuela, where
      intestinal helminths are endemic. As would be expected, in children over 5 years
      of age, the IgE levels were highly elevated, and in addition, the cord blood
      serum levels were higher than those reported for populations where parasitic
      infections are uncommon. However, the IgE levels measured in the sera of children
      under 5 years of age were relatively low, and within the generally accepted
      normal ranges. This was surprising because the latter children were infected by
      parasites and had high IgG antibody levels against helminths. We found, however,
      that whereas older children had detectable IL-4 levels in their sera, the younger
      children did not. These results suggest that, despite infection of these slum
      children by common intestinal helminths, a polyclonal stimulation of IgE
      synthesis did not occur, possibly due to a lack of IL-4 production by an immature
      immune system.

PMID- 8281341
TI  - Variations in the concentrations of airborne Olea pollen and associated
      pollinosis in Cordoba (Spain): a study of the 10-year period 1982-1991.
AB  - The amount and the seasonal and daily changes in the concentrations of Olea
      pollen grains in the atmosphere of Cordoba (Spain) have been studied over a 10
      year period. The year by year seasonal variation pattern and the theoretical
      intradiurnal variation model are presented. The data show a high annual
      variability, median concentrations varying from 75 g/m3/h in 1983 to 1413 g/m3/h
      in 1986. A steady increase in the total amount of pollen is attributed to the
      climatological characteristics of the period studied. On the other hand, the
      clinical data show that the number of cases of Olea allergy has increased
      considerably during this period, probably more because of changes in the quality
      of the atmosphere than because of the increase in the amount of antigen present
      in the air.

PMID- 8281342
TI  - Modulation of beta 2-adrenoceptors in lymphocytes of allergic patients after in
      vitro antigenic stimulation.
AB  - In this study, we assessed the effect of antigen-specific stimulation on beta
      adrenoceptors of human lymphocytes in order to study the beta-receptor atopy
      theory of Szentivanyi. Determination of these receptors was basically carried out
      as described by Brodde et al., utilizing [125I]-cyanopindolol as ligand in
      control and allergic patients before and after stimulation with specific antigen.
      We found that in vitro the specific antigen-antibody reaction induces a decrease
      in beta-adrenoceptors. This alteration takes place in patients with rhinitis and
      asthma with sensitization to Dermatophagoides and grass pollen, regardless of
      their baseline clinical status. Therefore, in view of the results, we question
      the validity of Szentivanyi's atopy theory. We hypothesize that the modification
      in the beta-adrenoceptor system is a consequence rather than the cause of the
      activity of atopic diseases.

PMID- 8281343
TI  - Efficacy and tolerability of nedocromil sodium versus placebo in chronic
      reversible obstructive airways disease.
AB  - In this 8-week, double-blind, comparative trial of nedocromil sodium (4 mg
      q.i.d.) versus placebo in 42 patients with chronic reversible obstructive airways
      disease, there was a trend in favor of nedocromil sodium compared to placebo in
      parameters assessed by patients (nocturnal symptom scores, evening PEFR values)
      and those assessed by clinicians (asthma severity scores) compared with baseline
      values. There was a statistically significant difference (p < 0.05) in favor of
      nedocromil sodium in the inhaled bronchodilator requirements in the last 2 weeks
      of treatment. Both patients' and clinicians' evaluation of the overall efficacy
      of treatment was significant in favor of nedocromil sodium (p < 0.01 and p <
      0.05, respectively). The treatments were well tolerated by the majority of
      patients. From these data, it can be concluded that nedocromil sodium (4 mg
      q.i.d.) is of value in the preventive treatment of chronic reversible obstructive
      airways disease.

PMID- 8281344
TI  - Plasma kallikrein amidolytic activity in patients with urticaria.
AB  - We have studied the plasma kallikrein amidolytic activity in healthy control
      subjects (inactive), patients with chronic urticaria (active) and patients with
      acute urticaria (active) from their admission to the emergency room (active) to
      the time after which their clinical symptomatology had disappeared (inactive). We
      found statistically significant differences (p < 0.01) in the active groups of
      urticaria patients. This leads us to believe that kallikrein participates in the
      development of symptomatology in these patients.

PMID- 8281345
TI  - Antibacterial IgE antibodies in children.
AB  - The presence of specific IgE antibodies directed against common microorganisms
      was analyzed in a population of children. These antibodies included Escherichia
      coli, Proteus spp., Pseudomonas spp., Klebsiella spp., Streptococcus spp. and
      Staphylococcus spp. The determination of these antibodies was done by
      radioimmunoassay. Comparisons were made according to the parameters of age and
      total IgE levels. These antibodies were found in a high proportion of the cases.
      Statistical analysis demonstrated that the different specific IgE antibodies were
      present in all children, none showing special relevance. All of the antibodies
      studied were found to be present in a higher number of cases in the groups of
      older children, and in the group of children with increased total IgE levels, a
      significantly higher number of cases with antibacterial specific IgE antibodies
      was observed. The presence and the variety of the antibodies might be conditioned
      by individual as well as environmental factors. The role of antibodies is not
      well known. Although they are frequently found in allergic children, there have
      not been enough cases studied to establish their involvement in allergy.
      Understanding the role of antibodies might be of interest in the study of
      allergic processes exacerbated by bacterial infections.

PMID- 8281346
TI  - Study of the sensitization to storage mites in a pediatric population in
      Barcelona.
AB  - We performed the following study in order to determine the prevalence and
      characteristics of sensitization to storage mites in children mostly from the
      city of Barcelona. All children over 3 years of age attending our unit for the
      first time due to respiratory problems were given cutaneous tests using the prick
      test for the house dust mites Dermatophagoides pteronyssinus and D. farinae, and
      the storage mites Acarus siro, Lepidoglyphus destructor and Tyrophagus
      putrescentiae. We carried out a RAST and conjunctival test when it was considered
      appropriate. Of a total of 356 children studied, 39 showed cutaneous
      sensitization to storage mites, which represented 11% of the population studied,
      and 20% of the total sensitized to mites. However, only 3 of these children were
      only sensitized to storage mites, the remaining 36 (92%) also showing
      sensitization to house dust mites. Of the storage mites studied, L. destructor
      was the most significant. A history of immunotherapy to mites was associated with
      a greater percentage of positive cutaneous tests to storage mites, although this
      was not the case with the RAST test.

PMID- 8281347
TI  - Tolerance to aspirin in aspirin-sensitive asthmatics. Methods of inducing the
      tolerance state and its influence on the course of asthma and rhinosinusitis.
AB  - Aspirin-sensitive asthma is a serious clinical problem, frequently involving
      dramatic exacerbation and sometimes even death after the accidental ingestion of
      aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). The majority of
      such asthmatics usually suffer from chronic rhinosinusitis and nasal polyps as
      well, and almost half of them from headaches. Widal et al. in 1922, and later,
      Zeiss and Lockey were able to elicit tolerance to aspirin (ASA). In all the
      studies performed so far, tolerance to ASA was achieved by giving double
      threshold ASA doses every day or every few hours. This method elicited severe
      dyspnea and sometimes pronounced extrabronchial sensitivity symptoms. From our
      previous studies, it appeared that the smaller the aspirin dose, the weaker the
      sensitivity symptoms, and that it is possible to induce tolerance after eliciting
      only very slight sensitivity reactions. Based on this observation, we elaborated
      a new method of eliciting aspirin tolerance by the daily administration of
      gradually increasing doses of aspirin starting with subthreshold doses. Applying
      this method, we achieved tolerance to aspirin without any adverse reactions. The
      patients in a tolerance state to ASA also tolerated well other NSAIDs, i.e.
      indomethacin and diclofenac. It is possible to maintain a tolerance state for a
      long time by the administration of ASA at proper intervals. It was shown that
      such a procedure may have a beneficial influence on the course of asthma and
      rhinitis. In our opinion, inducing and maintaining aspirin tolerance in aspirin
      sensitive asthmatics is indicated in the following situations: 1) the need to
      treat coexisting rheumatic diseases; 2) the need to treat coexisting intractable
      headaches; and 3) the need for symptomatic treatment of ASA-sensitive asthma and
      rhinitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281348
TI  - Urticaria induced by caffeine.
AB  - Caffeine has rarely been reported as the cause of allergic reactions. We describe
      a 10-year-old child who developed urticaria after the intake of coffee and cola
      beverages. The prick test and the oral challenge test with caffeine were both
      positive. Nevertheless, the oral challenge test with theophylline, another
      methylxanthine, was negative.

PMID- 8281349
TI  - Evaluation of lymphocyte proliferative responses to food antigens with regard to
      age and food-specific IgE antibodies in food-sensitive atopic dermatitis.
AB  - Peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis
      (AD), selected for sensitivity to hen's egg or cow's milk, showed significant
      proliferation in response to food antigens, ovalbumin or bovine serum albumin
      compared with PBMCs from nonatopic control subjects. The proliferative responses
      of PBMCs to food antigens were evaluated with regard to age and specific IgE
      antibodies to food antigens in food-sensitive patients with AD. There were no
      differences in proliferation between each age group, and the proliferation in
      patients with AD was significantly higher than in age-matched control subjects.
      There was no relationship between proliferative responses of PBMCs and specific
      IgE antibodies to food antigens in patients with AD. These results suggest that
      the responsiveness of lymphocytes to food antigens is independent of age and food
      specific IgE antibodies in food-sensitive patients with AD.

PMID- 8281350
TI  - Spontaneous in vitro IgE synthesis: modifications induced by immunotherapy.
AB  - In this study, we used an in vitro experimental model with peripheral mononuclear
      cells (PBMCs) capable of synthesizing IgE to study the possible parallelism
      between in vitro IgE synthesis and the findings obtained in vivo showing changes
      in serum IgE values during immunotherapy (IT). Blood samples were extracted from
      10 healthy subjects and 39 allergic patients for lymphocyte culture. Allergic
      patients were classified into five groups according to the time of IT. After
      incubation for 7 days at 37 degrees C, IgE values were assessed by means of a
      radioimmunoassay technique modified for low values. Likewise, total serum IgE was
      assessed. Spontaneous in vitro production of IgE in control individuals (G0) was
      significantly lower (p < 0.001) than the mean production in allergic patients
      (GA). When patients were grouped according to the time of IT, we observed that
      IgE values decreased during the course of IT. The significant differences found
      between allergic patients and control individuals eventually disappeared from the
      third year of treatment. We found a statistically significant positive
      correlation (r = 0.575, p < 0.001) between total serum IgE values and in vitro
      IgE production in all subjects. We conclude that IT induces a series of
      variations in lymphocyte IgE production in vitro, which consists of a significant
      decrease in IgE production from the second year of IT compared with that of
      patients without IT. IgE production eventually reaches levels similar to those in
      healthy subjects. The symptomatic recovery shown by all patients was associated
      with evident immunological changes, which confirms the clinical utility of this
      treatment in allergic diseases and the importance of its long-term effects.

PMID- 8281351
TI  - Linear monitoring of patients sensitive to Olea and grass pollens treated with
      immunotherapy based on glutaraldehyde-modified (allergoid) extracts.
AB  - Extracts modified with glutaraldehyde (allergoid) have been offered to
      allergologists for immunotherapy in the last few years as supposedly clinically
      effective agents that diminish undesirable side-effects (allergenicity vs.
      immunogenicity). In order to acquire experience in the use of this therapeutic
      resource, we monitored a group of patients with pollinosis sensitive to Olea,
      grass pollens or both, who suffered from seasonal rhinoconjunctivitis (SRC) or
      rhinoconjunctivitis and seasonal asthma (RCSA) and were administered allergoid
      treatments standardized in biological units (HEP). The patients were monitored by
      determination of specific IgE and IgG4, endpoint prick tests and conjunctival
      provocation tests (CPT) with two types of antigen: Lolium perenne and Olea
      europaea. Measurements were made at baseline (T1), when the maximal tolerated
      dose had been given (T2) and 1 year after the treatment was started (T3).
      According to our results, this type of extract is tolerated quite well and causes
      no alterations in specific IgG4 or IgE levels. On the other hand, it features
      significantly decreased allergen-specific skin reactivity and increased response
      thresholds to the CPT (p < 0.01). A high correlation between skin and
      conjunctival provocation tests was observed at some stages (r = 0.79, p < 0.01).

PMID- 8281352
TI  - The effect of loratadine on activated cells of the nasal mucosa in patients with
      allergic rhinitis.
AB  - The effect of loratadine on the numbers of activated cells--cells expressing
      interleukin-2 receptors(IL-2R), HLA-DR antigens and proliferating cell nuclear
      antigen (PCNA)--in the nasal mucosa was studied in 48 patients with allergic
      rhinitis. Patients were treated with either loratadine (10 mg) or placebo for 1
      month. At the end of treatment, a significant decrease in the symptom scores was
      noted in both groups of patients. However, the clinical score was significantly
      lower in the loratadine group compared to the placebo group. At the end of
      treatment, the numbers of IL-2R+, HLA-DR+ and PCNA+ cells were significantly
      decreased only in the group on loratadine. An almost significant correlation was
      also observed between the numbers of IL-2R+ cells and symptoms in the loratadine
      group. Our results show that loratadine exerts its beneficial effect possibly by
      inhibiting both the action of histamine and immune activation.

PMID- 8281353
TI  - Mite allergy in the tropics: sensitization to six domestic mite species in
      Cartagena, Colombia.
AB  - Sensitization to the domestic mites Blomia tropicalis, Chortoglyphus arcuatus,
      Lepidoglyphus destructor and Aleuroglyphus ovatus was investigated in 77 subjects
      with clinical symptoms of asthma and/or allergic rhinitis and a positive skin
      prick test (wheal > or = 3 mm) to Dermatophagoides pteronyssinus and/or D.
      farinae. Seventy patients were skin test-positive to D. pteronyssinus and 73 to
      D. farinae. Serum samples from 29 nonallergic, skin test-negative individuals
      were used as negative controls. Specific IgE was determined by RAST and the
      results expressed as the % of the total counts bound (% TCB). A positive result
      (> or = 1% TCB) to D. farinae was detected in 89.6% of subjects, to B. tropicalis
      in 80.5%, to D. pteronyssinus in 75.3%, to C. arcuatus in 71.4%, to A. ovatus in
      68.8% and to L. destructor in 59.7%. None of the controls had a positive RAST to
      any of the mite species. Different IgE binding patterns were observed among these
      subjects, suggesting sensitization to unique as well as common allergens in the
      different mite species. Sensitization to Pyroglyphidae (D. pteronyssinus and D.
      farinae) and non-Pyroglyphidae mites (B. tropicalis, C. arcuatus, L. destructor
      and A. ovatus) is common among allergic individuals in Cartagena. Extracts of
      these mites may be needed for a more accurate diagnosis and effective treatment
      of respiratory diseases due to mite allergy in tropical environments.

PMID- 8281354
TI  - Pulmonary function abnormalities in patients with primary Sjogren's syndrome.
AB  - Thirty-two patients with primary Sjogren's syndrome (SS) were studied in order to
      determine the frequency of pulmonary disease using respiratory function tests.
      Eleven of the 32 patients revealed positive symptoms compatible with lung
      disease, including dyspnea, dry or productive cough and pleuritic pain. Seven of
      these 11 patients also showed a positive physical examination, and 5 showed
      abnormal chest roentgenograms. Restrictive lung disease was detected in 28.1% of
      the patients, obstructive disease in 21.8%, and 25% showed a combination of these
      features (mixed disease). Only 8 patients had completely normal function. There
      was no significant relationship between respiratory changes and age, smoking
      habits or glandular and extraglandular manifestations. Positive antinuclear
      antibodies (p < 0.03) detected by the indirect immunofluorescence test, and anti
      SS-A(Ro) and anti-SS-B(La) antibodies (p < 0.009) detected by Ouchterlony
      occurred more frequently in those patients with primary SS and restrictive
      pulmonary disease. The patients with anti-SS-A(Ro) and anti-SS-B(La) antibodies
      also showed significantly lower values for total lung capacity (TLC) (p < 0.0001)
      and forced vital capacity (FVC) (p < 0.0005) than patients without these serum
      abnormalities. The study of primary SS may help to elucidate the prevalence of
      lung abnormalities and their relationship with serum autoantibodies.

PMID- 8281355
TI  - Seasonal versus perennial immunotherapy: evaluation after three years of
      treatment.
AB  - We have performed a comparative study to evaluate seasonal and perennial
      schedules after 3 years of immunotherapy. Sixty patients suffering from rhinitis
      and/or asthma due to grass pollen sensitization were randomly allocated to
      receive a semi-depot extract of Phleum pratense according to a perennial or
      seasonal schedule. The last year of the study, 14 patients were recruited as a
      control group without immunotherapy. The cumulative dose was 602 BU in the
      perennial group and 372 BU in the seasonal group. The frequency and severity of
      side-effects were similar and very low in both treated groups. The IgE level was
      significantly lower after perennial immunotherapy at the end of the first 2
      years. A seasonal decrease in specific IgG levels was observed in patients who
      interrupted immunotherapy, while this was not observed in patients under the
      perennial schedule. Symptoms and medication scores did not show differences
      between groups. Nevertheless, we found a significant difference between treated
      patients and the control group.

PMID- 8281356
TI  - Perforation of the nasal wall and hyper-IgE syndrome.
AB  - Hyper-IgE syndrome is basically characterized by recurrent infections, chronic
      eczematous lesions, specific IgE antibodies against Staphylococcus aureus and
      markedly high serum IgE values. We present the case of an 11-year-boy with no
      relevant personal or family history, who came to our Department with highly
      pruriginous papulovesicular skin lesions of 3 years' duration. He presented
      marked obesity (+4 SD) and micropapulovesicular lesions in the trunk and
      extension areas of the limbs. The rest of the physical exploration was normal.
      Complementary studies revealed peripheral eosinophilia, increase in globular
      sedimentation rate and IgE values of 20,000 IU/ml, a nonspecific reaction to skin
      tests, and a skin biopsy compatible with atopic dermatitis. Three months later,
      he presented eczematous lesions in the trunk and limbs, perforation of the nasal
      wall due to staphylococcal abscess (diagnosed by biopsy), bilateral maxillary
      sinusitis and IgE values of 59,238 IU/ml. The differential diagnoses are
      discussed, as well as new diagnostic-therapeutic possibilities.

PMID- 8281357
TI  - Deliberate release of a recombinant vaccinia-rabies virus for vaccination of wild
      animals against rabies.
AB  - Since 1978, several European countries have conducted, at different times, large
      scale field trials of oral vaccination of foxes (Vulpes vulpes) against rabies,
      using the SAD, standard or B19-modified attenuated strains of rabies virus. The
      use of attenuated strains of rabies virus remains controversial as far as safety
      and stability are concerned, since these virus strains retain pathogenicity for
      rodents or other wildlife species and are heat-sensitive. To improve both safety
      and stability of the vaccine used in the field, a recombinant vaccinia virus
      expressing the immunogenic G protein of rabies virus has been developed and
      released in the field. The first safety-efficacy results are very encouraging.

PMID- 8281358
TI  - Overproduction of indole acetic acid in Azospirillum lipoferum using the
      Escherichia coli trp operon.
AB  - A recombinant plasmid carrying the trp operon from Escherichia coli, which
      synthesizes tryptophan from chorismate, was constructed by using a broad host
      range plasmid vector pRK290; a mutant trp plasmid for tryptophan overproduction
      was then selected. The physiological, biochemical, and genetic properties of the
      Azospirillum lipoferum KY6, a potential nitrogen fixer of rice, harbouring the
      recombinant trp plasmid pMJC1 and its mutant pMJC101, were compared with those of
      the wild-type bacteria. Anthranilate synthetase is known to be the trpE gene
      product which plays a key role in the regulatory step in the feedback control of
      tryptophan biosynthesis. The enzyme activity of the Azospirillum lipoferum KY6
      carrying pMJC1 or pMJC101 was respectively 7- and 30-fold higher than that of the
      wild type in the presence of 10(-4)M tryptophan. As expected, the amount of
      tryptophan biosynthesis in A. lipoferum KY6 (pMJC101) was increased approximately
      100-fold as compared with the wild type, which led to overproduction of indole
      acetic acid even without addition of exogenous tryptophan. Moreover, the
      recombinant trp plasmid was fairly stable in A. lipoferum KY6 host, showing only
      25% loss of the plasmid itself or the trp insert after 40 generations.

PMID- 8281359
TI  - In vivo transfer of pR68.45 from Pseudomonas aeruginosa into indigenous soil
      bacteria.
AB  - The release of genetically engineered organisms (GEMs) into the environment could
      result in novel gene sequences becoming transferred to, and established in, the
      indigenous soil biota. The potential for recombination in nonsterile soil is
      difficult to determine due to problems isolating transconjugants of indigenous
      microbes, while concurrently suppressing introduced donors. We have developed a
      system that allows us to detect the transfer of the plasmid R68.45 from
      Pseudomonas aeruginosa strain PA025 into the indigenous soil bacterial
      population. Transconjugants were selected by plating on minimal media containing
      antibiotics and were verified by DNA-DNA hybridization. The observed maximum
      transfer frequency was approximately 10(-6). Fatty acid analysis of
      transconjugants showed that intergeneric transfer was occurring between the
      introduced organism and genetically dissimilar species.

PMID- 8281360
TI  - Low-temperature scanning electron microscopy in fungus-nematode interaction.
AB  - A comparative study has been made of different preparation techniques used for
      the scanning electron microscope (SEM), with regard to their application to
      fungus-nematode interaction. The preparation of frozen-hydrated specimens of both
      healthy and Arthrobotrys-oligospora-infected second-stage larvae of the root-knot
      nematode (Meloidogyne sp.) is described, and the results are compared with those
      obtained by critical point-drying and freeze-drying. In all cases the frozen
      hydrated specimens consistently showed the best preservation.

PMID- 8281361
TI  - Video-rate confocal reflection microscopy of neoplastic cells: rate of
      intracellular movement and peripheral motility characteristic of neoplastic cell
      line (RSK4) with high degree of growth independence in vitro.
AB  - Video-rate laser confocal interference reflection microscopy was used to
      demonstrate rapid motion of intracellular organelles and features at the cell
      periphery in a fully transformed neoplastic cell line, RSK4, and in four other
      neoplastic cell populations. In the RSK4 cells, vibrational and trafficking
      movements of intracellular particles at a rate greater than 25 Hz and ranging
      down to 5 Hz were recorded. Rapidly moving processes changed to ruffles, then
      microspikes, and previously undetectable ephemeral intercellular contacts were
      seen. Dynamic cyclical changes were revealed in the sizes of the podosomal close
      contacts of the transformed cells. The visibility of such features and the
      temporal and spatial resolution are improved over earlier methods. The fact that
      fast cellular and intracellular movements can be detected with this microscopic
      technique offers new possibilities in attempting to recognise differences between
      unimpaired living cells, and it may prove useful in the identification of
      malignant cells.

PMID- 8281362
TI  - Cholesterol and coronary heart disease in women: an overview of primary and
      secondary prevention.

PMID- 8281363
TI  - Estrogen: risk versus benefit for the prevention of coronary artery disease.

PMID- 8281364
TI  - Coronary artery disease in women: differences in diagnosis, therapy, and
      prognosis.

PMID- 8281365
TI  - Treatment of hypercholesterolemia in the elderly: is cholesterol a risk factor
      and should it be treated?

PMID- 8281366
TI  - Prevention of coronary disease starting in childhood: what risk factors should be
      identified and treated?

PMID- 8281367
TI  - Thrombolytic therapy in selected patients with impending myocardial reinfarction.
AB  - BACKGROUND: In selected patients with postinfarction angina and impending
      reinfarction, thrombolysis with recombinant tissue-type plasminogen activator (rt
      PA) or streptokinase is highly effective in avoiding a new myocardial infarction.
      METHODS: To avoid major cardiac events, we treated 14 consecutive patients with
      thrombolytic therapy because of impending reinfarction with ECG ST-segment
      elevation. Thirteen patients received rt-PA (100 mg over 3 hours), and one
      patient received streptokinase (1.5 million IU over 1 hour). All patients had
      failed to respond to maximal medical therapy with intravenous nitrates, beta
      blockers, Ca-antagonists, heparin, and opiates. RESULTS: In all patients,
      clinical and ECG signs of acute ischemia resolved completely within 1 hour after
      beginning thrombolysis, and no patient developed biochemical markers of
      myocardial infarction. Ten patients underwent coronary angiography: five had
      three-vessel disease, two had two-vessel disease, and three had one-vessel
      disease. The culprit lesion was located in the left anterior descending artery in
      eight cases and the right coronary artery in two. No patient showed intracoronary
      thrombus. Four patients underwent successful, semiurgent percutaneous
      transluminal coronary angioplasty; three received an elective and two an urgent
      coronary artery bypass graft. CONCLUSIONS: Thrombolysis (or repeated
      thrombolysis) is effective in selected patients with clinical ECG signs of
      impending reinfarction. It can temporarily stabilize the condition of many
      patients, thus allowing safer mechanical revascularization to be performed.

PMID- 8281368
TI  - Incremental prognostic value of thallium imaging and coronary angiography in
      patients with a symptom-limited ECG stress test.
AB  - BACKGROUND: This study evaluates the incremental prognostic value of qualitative
      thallium-201 imaging and coronary angiography in patients with suspected or known
      coronary artery disease. METHODS: Within 1 month, 150 patients underwent
      diagnostic symptom-limited ECG stress test, thallium imaging, and coronary
      angiography. The incremental power of sequentially performed tests was evaluated
      by the overall likelihood ratio statistic. RESULTS: At 3-year follow-up, 16
      patients had died from a cardiac cause, 12 had suffered a nonfatal myocardial
      infarction, and 34 had undergone revascularization procedures more than 60 days
      after testing. Considering hard events, thallium imaging did not improve the
      prognostic information provided by clinical exercise stress test data, while
      coronary angiography increased the predictive power of the combined, exercise
      stress test, and scintigraphic data (P < 0.001). Moreover, when thallium results
      were added to clinical, exercise, and coronary angiographic data, the predictive
      power was unchanged. When the analysis was repeated including the occurrence of
      late revascularization procedures, each test showed additional prognostic
      information to that obtained by the other combined tests (P < 0.001).
      CONCLUSIONS: This study demonstrates that in patients with a symptom-limited ECG
      stress test, coronary angiography adds prognostic information to combined
      clinical, exercise ECG, and thallium imaging data. The incremental prognostic
      value of qualitative thallium imaging is demonstrable only when late
      revascularization procedures are included as events.

PMID- 8281369
TI  - Peroxide plasma level in patients with coronary heart disease as a possible
      indicator of ischemia during exercise test.
AB  - BACKGROUND: This study evaluated the possible changes in production of free
      oxygen species during myocardial ischemia in the course of exercise testing of
      ischemic coronary disease. METHODS: Exercise testing was performed on 58 patients
      with suspected ischemic coronary disease. Plasma hydrogen peroxide (H2O2) level
      was assayed according to Frew et al. (Anal Chim Acta 1983, 155:139-150) in venous
      blood samples obtained before the test, at submaximal and maximal work loads, and
      after 30 minutes of rest. RESULTS: Hydrogen peroxide plasma level significantly
      increased (P < 0.001) at maximal work load in patients with positive exercise
      test results. Patients with negative exercise test results initially manifested a
      higher H2O2 level that dropped during maximal work load. CONCLUSIONS: The rise in
      plasma H2O2 level during myocardial ischemia indicates that intensification of
      oxygen free radical production occurs. This may be the result of hypoxanthine
      conversion by xanthine oxidase, catecholamine auto-oxidation, polymorphonuclear
      neutrophil activation, and/or derangement within mitochondrial electron transfer.
      The noticed difference between patients with a positive exercise test and those
      diagnosed as without ischemia may be of clinical relevance.

PMID- 8281370
TI  - The protection by ischemic preconditioning against myocardial ischemia- and
      reperfusion-induced arrhythmias is not mediated by ATP-sensitive potassium
      channels in rats.
AB  - BACKGROUND: Single or multiple brief periods of myocardial ischemic
      preconditioning (PC) limits ischemia- and reperfusion-induced arrhythmias. This
      study tested whether PC protects against ischemia/reperfusion-induced arrhythmias
      and, if so, whether the protective effect was mediated by the opening of ATP
      sensitive (KATP) channels. METHODS: In protocol 1, the effects of PC (three
      cycles of 2 minutes of coronary occlusion and 5 minutes of reperfusion) on the
      development of arrhythmias after a coronary occlusion of 5, 10, or 20 minutes
      followed by 10 minutes of reperfusion were studied in rats. In protocol 2,
      solvent or a KATP channel blocker (glyburide [0.64 mg/kg body weight delivered
      intravenously]) was administered 5 minutes before PC. In a second group,
      glyburide was administered immediately after PC. In a third group, solvent,
      glyburide, or a KATP channel opener (pinacidil [0.16 mg/kg delivered
      intravenously]) was administered 5 minutes before coronary occlusion for 5
      minutes without PC. RESULTS: In protocol 1, PC significantly reduced the ischemia
      induced ventricular premature beats (VPBs) and ventricular tachycardia (VT), and
      it abolished ischemia-induced ventricular fibrillation (VF) during 10 or 20
      minutes of coronary artery occlusion. PC also significantly reduced reperfusion
      induced ventricular arrhythmias after 5 or 10 minutes of coronary artery
      occlusion; this effect of PC, however, was lost during reperfusion after 20
      minutes of coronary occlusion. In protocol 2, PC again produced a marked
      reduction in reperfusion-induced arrhythmias and abolished the incidence of VPBs
      during 5 minutes of ischemia as well as the incidence of irreversible VF during
      reperfusion, whereas glyburide did not block the protective effect of PC on
      ischemia- and reperfusion-induced arrhythmias. Glyburide administered in non-PC
      animals did not reduce ischemia- and reperfusion-induced arrhythmias, nor did
      pinacidil. CONCLUSIONS: The protective effect of PC was not attenuated by
      glyburide. These results suggest that the protective effect of PC in ischemia-
      and reperfusion-induced arrhythmias is not likely to be related to activation of
      KATP potassium channels during ischemia in rats.

PMID- 8281372
TI  - Early assessment of the success of thrombolytic therapy by noninvasive markers.

PMID- 8281371
TI  - Left main coronary artery stenosis after aortic valve replacement: genetic
      disposition for accelerated arteriosclerosis after injury of the intact human
      coronary artery?
AB  - BACKGROUND: Left main coronary artery stenosis is a rare but life-threatening
      complication after aortic valve replacement because of coronary perfusion-related
      trauma to the vessel wall with cannulation of the coronary ostia. We investigated
      whether this complication still occurs in the 1990s despite the use of more
      advanced catheter materials and modern surgical preservation techniques. METHODS:
      Four years after identification of the first two cases in 1987, five further
      patients had developed left main coronary artery stenosis after aortic valve
      replacement (incidence, 0.9%) at the cardiothoracic clinic of the J.W. Goethe
      University and were studied for contributing factors. RESULTS: Severe coronary
      ostial stenosis developed within 1 to 6 months after aortic valve replacement. In
      one such case, intimal proliferation was seen in a biopsy specimen that was
      comparable to the restenosis induced by coronary angioplasty. The clinical
      characteristics of the patients developing the complication, the surgical
      technique, and the intraoperative course did not differ from the other patients.
      However, five of the seven patients (71%) had a common genetic trait concerning
      their apolipoprotein E genotype (the epsilon 4 allele) that is normally present
      in only 10% to 15% of patients screened (P < 0.01). CONCLUSIONS: These lesions
      seem to result from a uniform response of the vessel wall to injury. Their
      incidence is probably related in part to the degree of injury after trauma to the
      coronary ostia during cannulation for myocardial protection. Patients with the
      epsilon 4 allele might be genetically predisposed for a pathologically increased
      response of proliferative repair mechanisms after arterial injury. The
      complication can be avoided by not instrumenting the coronary ostia for direct
      antegrade cardioplegia but using retrograde delivery as an alternative method of
      myocardial protection.

PMID- 8281373
TI  - Bibliography of the current world literature.

PMID- 8281374
TI  - Improving the evaluation of renal transplant collecting system dilatation by
      computerized ultrasound image digitization.
AB  - 43% of the renal allografts transplanted at our centre demonstrate pelvicalyceal
      dilatation on ultrasonography. However, only 6% of grafts are ultimately shown to
      be obstructed by antegrade pyelography. We have attempted to improve the
      specificity of ultrasonography by a quantitative analysis of 394 serial
      ultrasound studies from 150 renal transplant recipients. Representative images in
      the longitudinal and transverse axes were selected by a single observer for each
      of the studies and the outline of the kidney and its pelvicalyceal system was
      traced out. The images were then digitized using a Summagraphics tablet so that
      the length, width and area of the kidney and its pelvicalyceal system were
      calculated for each image. A step-wise discriminant analysis was performed which
      showed that the ratio of the area of the kidney to its pelvicalyceal area in both
      axes discriminated between normal, dilated but non-obstructed, and obstructed
      grafts. The median ratio of kidney to collecting system area in the obstructed
      grafts was 5.2 in the longitudinal and 4.4 in the transverse scan planes (vs
      median ratios of 32.8 and 22.0 for non-dilated grafts). Using canonical
      discriminant function, an index was derived which combines these ratios for the
      longitudinal and transverse images of the same kidney and this has further
      improved the diagnostic accuracy (median index of 2.45 in obstructed group vs 
      0.85 in non-dilated kidneys). This method improves upon the radiologist's report
      and identifies those grafts which require intervention.

PMID- 8281375
TI  - Survival, patterns of spread and prognostic factors in uterine sarcoma: a study
      of 76 patients.
AB  - We have analysed the medical records and diagnostic imaging of 76 patients
      presenting to this hospital for treatment of uterine sarcoma between 1970 and
      1990. Patients were divided into those presenting before 1980 (n = 22) and after
      1980 (n = 54), when sectional imaging (ultrasound, CT scanning) and more modern
      radiotherapy and chemotherapy were introduced. No survival difference was
      observed between these two groups. In those patients presenting after 1980, the
      median age was 54 years (range 18-80), and median survival 22 months from initial
      diagnosis. Factors associated with a significantly improved survival included low
      grade (although not histological type) of initial tumour (p = 0.001) and Stage I
      disease at presentation (p = 0.006). In 17 patients receiving pelvic radiotherapy
      following initial surgery, both the time to relapse (p = 0.005) and overall
      survival (p = 0.045) were increased. Adjuvant chemotherapy in 19 patients did not
      improve outcome. Most diagnoses of relapse were established clinically; they
      occurred most frequently in the pelvis, followed by lung and abdomen. Pulmonary
      relapse was accompanied by spontaneous pneumothorax in two cases. Bone and brain
      metastases were uncommon (< 10%). Following diagnosis of relapse, the median
      survival was 9 months, with the outcome significantly worse if multiple
      metastatic sites were involved (p < 0.001). No survival benefit was demonstrated
      from either local radiotherapy or combination chemotherapy once relapse had
      occurred. Prognostic factors and current policies for the diagnosis and
      management of uterine sarcomas are discussed.

PMID- 8281376
TI  - Long source-skin distance rectal irradiation technique: a review of results.
AB  - Endocavitary rectal irradiation is a well established curative treatment for
      patients with selected early cases of adenocarcinoma of the rectum. At McGill we
      use a long source-skin distance (SSD) rectal irradiation technique as an
      alternative to the standard short SSD rectal irradiation technique originally
      described by Papillon. Eight patients, seven women and one man, were treated
      between April 1986 and November 1988. Median age was 72.5 years (range 46-86
      years). Seven patients were treated with curative intent, and one for palliation.
      The mean follow-up period for all patients was 43 months, with a median of 54
      months (range 3-65 months). Actuarial survival and disease-free survival were 86%
      and 72% at 65 months for the seven patients treated with curative intent.
      Treatments were well tolerated by all patients and only one patient developed
      localized proctitis that required steroid enemas, which resulted in complete
      resolution of symptoms. Our results are comparable with those in other reports in
      the literature. The complications were similar in type and frequency to other
      published series.

PMID- 8281377
TI  - Feasibility of patient immobilization for conventional cranial irradiation with a
      relocatable stereotactic frame.
AB  - The precision of patient repositioning and the firmness of immobilization are
      among the major determinants of the accuracy of radiation treatment delivery. A
      relocatable Gill-Thomas localizer (GTL) developed for neurosurgery and
      stereotactic radiotherapy achieves highly accurate relocation and immobilization
      and has been used successfully for fractionated stereotactic radiotherapy of
      intracranial lesions. The feasibility of using GTL for immobilization in
      conventional fractionated external beam radiotherapy was assessed by comparison
      with conventional Cabulite shell head fixation. The GTL was well tolerated at the
      time of preparation and during a 5 week course of radiotherapy. The principal
      advantage was superior relocation accuracy maintained throughout the course of
      treatment, high precision of field set-up and markedly reduced production time.
      In addition the time taken to position the patient in the treatment room was also
      marginally shortened. GTL is therefore a feasible method of head fixation for
      conventional cranial irradiation providing patients have adequate dentition. With
      further development the relocatable method of immobilization originally designed
      for stereotactic radiotherapy may become the preferred technique particularly in
      situations where high accuracy is desirable, such as stereotactically guided
      conformal radiotherapy.

PMID- 8281378
TI  - Late pulmonary scintigraphic defects after uneventful recovery from simple focal
      pneumonia of childhood.
AB  - We present a pilot study designed to determine whether pneumonia in children
      accompanied by focal consolidation on the chest radiograph (CXR) is associated
      with late abnormality as detected by radionuclide lung scintigraphy. 14 children
      with focal pneumonia were assessed 1 year after initial presentation. In 12 both
      krypton-81m ventilation and technetium-99m MAA perfusion studies were performed,
      while in two only perfusion studies were obtained. All cases had a further CXR.
      Abnormal or equivocal cases were reviewed clinically. Scans and CXRs were
      independently assessed by two observers and subsequently consensus reached by
      discussion. There were five abnormal and nine normal lung scans. Two defects
      matched the site of the initial pneumonia while three did not. A CXR at the time
      of lung scanning was normal except for one case with a small focus of
      consolidation on the opposite side to the initial pneumonia but with a normal
      lung scan. Similarly, clinical assessment at the time of scanning was
      unremarkable, with no history of further respiratory episodes except in one child
      excluded from the study because of an interval diagnosis of asthma. This pilot
      study indicates that lung scan defects are common in the medium term after
      supposedly uncomplicated pneumonia in childhood. The cause of these defects
      remains uncertain. The correlation with the site of the initial radiological
      abnormality is variable, pointing to the need for further research in this area.
      The importance of independent blind interpretation is also highlighted.

PMID- 8281379
TI  - Organ absorbed doses in intraoral dental radiography.
AB  - A dental radiography unit operating at 70 kV (nominal) and 20 cm focus-skin
      distance was used to irradiate an anthropomorphic phantom loaded with lithium
      fluoride thermoluminescent dosemeters, in order to assess the variation in organ
      absorbed dose with intraoral periapical radiographic view. 14 views using the
      bisecting-angle technique and four views using the paralleling technique were
      studied. The results are presented and the doses and dose distributions examined.
      Doses for the paralleling and bisecting-angle techniques are compared, and the
      effects of focus-skin distance and beam collimation upon patient dosimetry
      discussed. Sources of uncertainty in dental dosimetry studies using phantoms are
      also considered.

PMID- 8281380
TI  - Technical note: design features of the indwelling intrauterine tube for high dose
      rate intracavitary therapy for carcinoma of the cervix and some hints on its
      optimal use.
AB  - A description of the indwelling intrauterine tube to facilitate high dose rate
      brachyradiotherapy, with some clinical results, was published previously in this
      journal. This communication emphasizes some important design features of this
      tube, which ensures optimal efficiency and ease of use.

PMID- 8281381
TI  - Technical note: interstitial laser photocoagulation for the treatment of
      prostatic cancer.
AB  - Interstitial laser photocoagulation (ILP) is a new percutaneous technique for
      local ablation of deep-seated tumours. We have applied this to treat a focal
      abnormality in a patient with prostatic carcinoma, under local anaesthesia and
      sedation. Transrectal ultrasound and computed tomography (CT) were used to guide
      three 18G needles, inserted transperineally, into the abnormal area. A thin (0.8
      mm outer diameter) optical fibre was passed down each needle, so that the tip of
      the fibre lay within the tumour. The other end of the fibre was connected to a
      portable diode laser, which was activated at 2 W for 500 s. Real-time monitoring
      with ultrasound showed a gradually enlarging echogenic zone around the fibre-tip
      and a marked increase in colour Doppler signal; the echogenicity and Doppler
      signal decreased within a few minutes of completing treatment. Dynamic CT
      treatment 10 days later showed the treated area as a non-enhancing, avascular
      zone. Biopsies from this region confirmed the presence of necrosis. There were no
      complications. ILP appears to be a safe and effective way of ablating areas of
      focal abnormality in the prostate.

PMID- 8281382
TI  - Technical note: the safety of outpatient arteriography using 3F catheters.

PMID- 8281383
TI  - Technical note: appearances on ultrasound of impalpable injection port in a
      double chamber breast prosthesis.
AB  - Breast reconstruction utilizing tissue expansion is being increasingly practised
      by both plastic and general surgeons. Our current experience for both immediate
      and delayed reconstruction is with the double chamber Becker prosthesis. The
      prosthesis with the resulting breast mound has on occasions rendered the
      injection port difficult to localize by palpation. We have found ultrasound
      useful in identifying impalpable ports and in facilitating needle insertion into
      the injection dome.

PMID- 8281384
TI  - Case report: gallbladder perforation and bile leakage: diagnosis by colour
      Doppler sonography and percutaneous treatment.

PMID- 8281385
TI  - Case report: malignant giant cell tumour of the pancreas presenting as a large
      pancreatic cyst.
AB  - Carcinoma of the pancreas is a common tumour. Histologically, the majority are
      adenocarcinomas of duct origin. Carcinomas of the pancreas containing giant cells
      are uncommon and those containing osteoclast-type tumour cells are very rare. We
      report a case of malignant giant cell tumour presenting as an extremely large,
      thin walled haemorrhagic cyst of the pancreas. This tumour is most unusual in
      that the wall is composed of multiple highly pleomorphic malignant-looking
      multinucleated giant cells as well as numerous osteoclast-like giant cells in a
      stroma of small spindle shaped mononuclear cells.

PMID- 8281386
TI  - Case report: cranial fasciitis in childhood.

PMID- 8281387
TI  - Case report: hypomagnesaemia in a patient with acromesomelic dysplasia.
AB  - Hypomagnesaemia and acromesomelic dwarfism are both rare inherited disorders. We
      report the first case of both these conditions occurring in the same patient. Our
      child and his family pedigree are further evidence that both these diseases are
      inherited as autosomal recessive conditions. There is no known association
      between these two diseases.

PMID- 8281388
TI  - Case of the month: a calcified brain.

PMID- 8281389
TI  - CT--an increasingly important slice of the medical exposure of patients.

PMID- 8281390
TI  - Review article: effect of nuclear medicine on paediatric imaging.

PMID- 8281391
TI  - Improved detection of abnormal left ventricular wall motion using tomographic
      radionuclide ventriculography compared with planar radionuclide and single plane
      contrast ventriculography.
AB  - Tomographic radionuclide ventriculography is a technique which could have major
      advantages over conventional planar imaging, such as better assessment of
      ventricular wall motion abnormalities. This possibility was therefore
      investigated in 100 consecutive patients undergoing routine cardiac
      catheterization. Following angiography, planar blood pool images were
      conventionally acquired and tomographic imaging performed using the Aberdeen
      Section Scanner. All derived wall motion data were subsequently analysed in an
      objective and blinded manner. The mean age was 56 (range 33-71) and 79% were
      male. 67 patients had experienced prior myocardial infarction, 27 were
      categorized as having significant and six insignificant coronary artery disease.
      The detection rates for patients with prior myocardial infarction were 95% for
      angiography, 57% for planar imaging and 90% for tomography. Even taking patients
      with only prior anterior myocardial infarction, the detection rates were 94%, 63%
      and 91% respectively. For those residual patients with significant coronary
      artery disease, the rates were 7%, 0% and 59% respectively. Overall for the
      detection of patients with significant coronary artery disease, the sensitivity
      was 70%, 40% and 81% respectively. Patients with insignificant coronary artery
      disease did not demonstrate any abnormalities using any method. These results
      demonstrate that tomography and angiography have similar detection rates in the
      presence of significant coronary artery disease and both are superior to planar
      imaging.

PMID- 8281392
TI  - Ovarian cystic teratomas: value of chemical fat saturation magnetic resonance
      imaging.
AB  - Chemical fat saturation (FS) magnetic resonance imaging (MRI) for the
      characterization of ovarian cystic teratoma was evaluated in 19 patients with 22
      lesions. The tumour was evaluated for signal intensity, location and size; the
      presence of chemical shift artefact, debris and fat-fluid level. Ovarian cystic
      teratoma was diagnosed prospectively if the mass contained fat and/or more than
      one type of internal pattern on (1) SE T1-, T2-, (2) SE T1-, T2-, FS T1-weighted
      images. A correct diagnosis was reached in 17 of 22 tumours on conventional T1-
      and T2-weighted images, and in 21 of 22 tumours when fat-saturation images were
      added. When fat-saturation images were added, four of five tumours misdiagnosed
      on conventional images were then correctly diagnosed. These tumours contained
      only small amounts of fat. Fat-saturation images could detect smaller amounts of
      fat than conventional images. However, one tumour did not show decreased
      intensity on fat saturation images, and was not diagnosed even when fat
      saturation images were added. Fat saturation images have been shown to be of
      value in diagnosing cystic teratomas.

PMID- 8281393
TI  - Uterine sarcomas: a review of the Edinburgh experience from 1974 to 1992.
AB  - A retrospective review of patients treated for a uterine sarcoma in Edinburgh
      from 1974 to 1992 has been performed. Clinical details at presentation, tumour
      pathology, treatment and the outcome of treatment were all recorded. 82 patients'
      case notes were reviewed. 54 patients had died and 28 were alive (mean follow-up
      period 80.3 months). 39 patients had a malignant mixed mesodermal tumour, 12
      patients had an endometrial stromal sarcoma, and 27 had a leiomyosarcoma. Using a
      modified FIGO staging retrospectively, 41 patients had Stage 1 disease, two
      patients had Stage 2, 16 patients had Stage 3, and 13 patients had Stage 4
      disease. Definitive treatment of total abdominal hysterectomy and bilateral
      salpingo-oophorectomy was used in 69 patients, with 35 of these patients also
      receiving post-operative radiotherapy to the pelvis. 13 patients did not undergo
      surgery. Five of these patients received radical radiotherapy, three patients
      received palliative radiotherapy, and five patients were not treated. The overall
      median survival is 15 months and the 5-year actuarial survival is 31%. 25 of the
      26 surviving patients had Stage 1 disease at presentation. Post-operative pelvic
      radiotherapy did not influence either survival or local tumour control. 51 of the
      54 patients who relapsed had evidence of distant metastases. We conclude that
      total abdominal hysterectomy and bilateral salpingo-oophorectomy remains the
      treatment of choice for uterine sarcomas.

PMID- 8281394
TI  - Extracorporeal shock wave lithotripsy for ureteric calculi with the Dornier
      MFL5000 lithotriptor at a multi-user centre.
AB  - We have reviewed 241 consecutive cases of ureteric calculi managed with the
      Dornier MFL5000 lithotriptor. The patients were individually managed by 24
      visiting urologists between October 1990 and September 1991. There were 153 cases
      of upper ureteric calculi, of which 59 were successfully manipulated back to the
      renal pelvis prior to treatment, and 94 were treated in situ. There were 27 mid
      ureteric and 61 lower ureteric cases; in 51% of stones treated in situ ureteric
      stents were placed prior to extracorporeal shock wave lithotripsy. All stones
      were radio-opaque and localised with on-line fluoroscopy. The outcome of
      treatment was assessed at 3 months, with failure defined as residual calculi > or
      = 4 mm. The follow-up rate was 89%. The overall fragmentation rate after a single
      treatment was 72%, which increased to 81% with re-treatment. Of the upper
      ureteric calculi, manipulated stones had a significantly higher fragmentation
      rate (85%) compared with in situ stones (63%). The fragmentation rate was 89% for
      mid-ureteric stones and 71% for lower ureteric stones. Factors that significantly
      influenced fragmentation were retrograde manipulation of stone, number of
      impulses delivered and age of the patient. Stone size, the presence of a ureteric
      stent and mode of anaesthesia did not significantly influence fragmentation.
      These results suggest the Dornier MFL5000 lithotriptor is effective for the
      management of ureteric calculi in a multi-user setting.

PMID- 8281395
TI  - Long-term stone regrowth and recurrence rates after extracorporeal shock wave
      lithotripsy.
AB  - We reviewed 1055 patients with symptomatic urinary calculi treated by
      extracorporeal shock wave lithotripsy (ESWL) monotherapy to determine the long
      term stone regrowth and recurrence rates as correlated with the pre-treatment
      stone burden, site and multiplicity. Long-term follow-up (mean 75.8 months) was
      available in 94 patients, representing 106 renal units. The recurrence of stone
      was defined as reappearance of stone on follow-up plain abdominal radiographs.
      The regrowth of stone was defined as stone regrowing larger than one-third of the
      original residual size. A stone-free rate of 53% was achieved. The overall stone
      regrowth and recurrence rates were 26 and 15% respectively. It was concluded that
      the stone recurrence rate after ESWL was not influenced significantly by the
      stone size or the multiplicity, but that the regrowth rate was. Stone recurrence
      and regrowth rates after ESWL were both influenced by the stone location.

PMID- 8281396
TI  - Management of blunt renal trauma.
AB  - The management of major renal lacerations after blunt trauma is still a matter of
      controversy. In this study, conservative treatment of major renal lacerations
      failed in 7 of 18 patients, leading to delayed surgery. Urography after blunt
      trauma was abnormal in 97% of patients with severe renal injury but a normal
      urogram did not exclude severe renal injury. Computed tomography had a greater
      degree of accuracy than urography and ultrasonography in determining the extent
      of the injury and was more practical to perform than angiography. The results
      indicate that patients with significant extrarenal leakage on urography,
      angiography or CT should receive immediate surgical management.

PMID- 8281397
TI  - Primary use of a double J silicone ureteric stent in renal transplantation.
AB  - Vesicoureteric leakage and obstruction are the commonest urological complications
      after renal transplantation. A retrospective analysis of our initial experience
      using a double J silicone ureteric stent showed that primary splinting of the
      vesicoureteric anastomosis eliminated these complications, whereas their combined
      incidence was 13.6% in the non-stented patients. The presence of the stent was
      not associated with increased risks of urosepsis.

PMID- 8281398
TI  - Recovery of ureteric motility following complete and partial ureteric
      obstruction.
AB  - Complete and partial ureteric obstruction was created in 2 groups of 10 mongrel
      dogs by placing a ligature around, or inserting a fine bore plastic stent into,
      the lower end of the left ureter (Groups 1 and 2). After 4 weeks the ligature or
      stent was removed, a 2.5-cm segment of ureter was harvested for in vitro analysis
      and the ureter reimplanted into the bladder. Pelvic and ureteric pressures and
      motility were recorded before, during and after the period of obstruction via a
      subcutaneously placed nephrostomy tube. Pre-obstruction resting intra-ureteric
      pressure was 2.1 +/- 0.3 mm Hg (mean +/- SEM), with regular contractions 8.9 +/-
      0.7/min of 36.2 +/- 1.2 mm Hg amplitude. After 4 weeks of obstruction,
      contractility was abolished in Group 1 but increased in Group 2, 71.5 +/- 3.3 mm
      Hg, with irregular multiphasic contractions seen following diuresis. Intra
      ureteric pressure was 16.3 + 1.2 mm Hg in Group 1 and 9.3 + 1.2 mm Hg in Group 2.
      In vitro experiments confirmed the patterns of contractility seen in vivo. Eight
      weeks after reimplantation the ureter returned to normal rhythm and rate in Group
      1, but increased contractility persisted both in vivo and in vitro in Group 2.

PMID- 8281399
TI  - Frequency-volume chart pattern in a healthy female population.
AB  - Very few data are available on what should be considered a normal frequency
      volume chart. To establish baseline figures we studied the voiding diaries of 33
      normal women. A computer program was developed using 12 parameters. A normal
      pattern was established for young and middle-aged women. These data may be used
      as a reference when analysing the charts of patients with voiding dysfunction.

PMID- 8281400
TI  - Quantification of bladder outlet obstruction by measurement of urethral opening
      pressure using an adapted fluid bridge test.
AB  - A new technique for measuring urethral opening pressure above the distal
      sphincter is described, based on the fluid bridge test. This test eliminates many
      of the inaccuracies produced when using standard pressure flow studies. Nineteen
      males were studied, 15 of whom had cystometric evidence of bladder outlet
      obstruction, the other 4 being unobstructed. The mean urethral opening pressure
      in the obstructed group was 69 cm H2O (range 44-124) and in the unobstructed
      group 19 cm H2O (range 16-22). The test is simple to perform and is not affected
      by muscular activity in the pelvic floor or the time lag between detrusor
      pressure and flow rate measurement.

PMID- 8281401
TI  - The contribution of magnetic resonance imaging of the pelvic floor to the
      understanding of urinary incontinence.
AB  - The anatomy of urinary incontinence and the underlying pathology is still under
      discussion. We examined 24 stress incontinent patients and 6 healthy volunteers.
      Magnetic resonance imaging (MRI) clearly shows that the urethra is not connected
      to the levator ani. The urethra is not fixed to deep perineal muscle layers. In
      stress incontinence the sharp angulation of the levator ani of healthy volunteers
      is lost in 65%. MRI shows degeneration of the levator ani muscle in 45% of stress
      incontinent patients. The extent of damage to the levator can clearly be
      identified with the aid of MRI.

PMID- 8281402
TI  - Intravesical oxybutynin chloride and clean intermittent catheterisation in
      patients with neurogenic vesical dysfunction and decreased bladder capacity.
AB  - Oral administration of oxybutynin chloride is effective in increasing bladder
      capacity in patients with neurogenic bladder dysfunction who are practising clean
      intermittent catheterisation, but it is often associated with systemic side
      effects. The effect of intravesical instillation of oxybutynin chloride was
      studied in 14 patients who were practising clean intermittent catheterisation and
      in whom the maximum cystometric capacity was < 250 ml and/or vesical compliance <
      5. A 5-mg tablet of oxybutynin chloride was crushed and suspended in 10 ml of
      boiled and cooled water and instilled into the bladder after emptying it
      completely; this was carried out thrice daily either by the patient or by his
      carer. During follow-up (6-12 months) no local or systemic side effects were
      observed and patient compliance was excellent in 12 patients, who showed an
      increase in maximum cystometric capacity and vesical compliance. One patient
      could not retain the drug intravesically because of reflex detrusor contraction
      and he was excluded from the study. One patient was lost to follow-up. The
      results suggest that the intravesical instillation of oxybutynin chloride is safe
      and effective in the treatment of selected patients with neurogenic bladder
      dysfunction whose bladder capacity is small and who are practising clean
      intermittent catheterisation.

PMID- 8281403
TI  - Response of isolated human neurogenic detrusor smooth muscle to intramural nerve
      stimulation.
AB  - The effect of intramural nerve stimulation of isolated strips of human detrusor
      was investigated and compared with the response of isolated detrusor strips of
      control bladders. All patients with neurogenic bladder underwent ileocystoplasty
      in order to resolve intractable incontinence and/or vesicoureteric reflux due to
      low compliance or severe detrusor uninhibited contractions. The response of
      isolated strips of neurogenic bladder to field stimulation was significantly
      greater than the response of isolated strips of control bladders. Tetrodotoxin
      virtually eliminated the response to field stimulation for both groups. Atropine
      (10(-6)M) almost completely inhibited the response of control bladder strips to
      field stimulation (4% of the response remaining), whereas the responses of the
      strips from neurogenic bladders were inhibited by approximately 70%. Low dose KCl
      (5 and 10 mM) significantly enhanced the detrusor contractility of control
      bladders, whereas the response of neurogenic bladders was unchanged. The
      responses of both groups were significantly inhibited in the presence of 20 mM
      KCl. The dose response curves and the ED50 values for KCl were similar for both
      neurogenic and control bladders. The rate of reduction of the response to field
      stimulation in the presence of zero calcium medium was significantly smaller for
      the isolated strips of neurogenic bladders than for the control bladders.

PMID- 8281404
TI  - Urodynamic and clinical aspects of ileal low pressure bladder substitutes.
AB  - Twenty-three patients with an ileal bladder substitute formed after cystectomy
      for invasive bladder cancer were evaluated clinically and urodynamically between
      3 and 38 months post-operatively. The urodynamic measurements were compared with
      the clinical findings. After re-education of the patients' voiding habits the
      mean voiding volumes of the bladder substitutes stabilised 6-9 months post
      operatively at 350 ml. The frequency of micturition was 3 to 5 times during the
      day and once or twice at night. The maximum functional capacity (maximum voiding
      volume) was about 490 ml. Ninety-one per cent of the patients were continent
      during the day 18 months after the operation and 82% were continent during the
      night. Micturition was problem-free with an average maximum flow of 25 ml/s and
      an average micturition time of 50 s. The mean voiding volume of ileal bladder
      substitutes was 50% of the measured cystometric capacity; the maximum functional
      capacity (= max. micturition volume) was 80% of the cystometric capacity. The
      average basal pressure was < 20 cm H2O from the third post-operative month
      onwards. Eleven of the 23 patients had contractions in the bladder substitute
      (average at 30 cm H2O) at 55-76% of the maximum cystometric capacity or at
      approximately 90% of the maximum functional capacity. Such spike waves had no
      clinical or radiological consequences. If the patients were shown how to increase
      the functional capacity of a reservoir made from only 40 cm of ileum, the
      clinical results were excellent.

PMID- 8281405
TI  - Growth fractions in bladder cancer defined by Ki67: association with cancer
      grade, category and recurrence rate of superficial lesions.
AB  - Predicting future tumour behaviour has always been a major task when treating
      bladder cancer. Ki67 monoclonal antibody has been reported to be a good marker of
      proliferative activity in a variety of tumours. We have studied the association
      of growth fractions defined by the monoclonal antibody with tumour grade,
      category and recurrence rate of superficial lesions in 34 patients with bladder
      cancer and 15 normal controls. Mean Ki67 indexes (% stained cells) were 0.07 +/-
      0.02% in normal urothelium, 1.27 +/- 1.55% in grade 1, 12.23 +/- 8.32% in grade 2
      and 16.42 +/- 11.82% in grade 3 tumours, while the values were 5.45 +/- 5.87%,
      12.66 +/- 9.81% and 17.18 +/- 12.41% in categories pTa, pT1 and T2-T3
      respectively. Recurrence and non-recurrence groups of patients showed indexes of
      13.29 +/- 9.49% and 4.15 +/- 5.0% respectively. Statistically significant
      differences in Ki67 values between normal urothelium and tumour, between tumours
      of different grades and categories as well as between recurrence and non
      recurrence groups of patients led to the conclusion that Ki67 monoclonal antibody
      is a good tool in defining tumour behaviour in bladder cancer.

PMID- 8281406
TI  - Glutathione-S-transferase pi expression in transitional cell carcinoma of the
      bladder.
AB  - Glutathione-S-transferase pi (GST pi) is a multifunctional protein that acts as
      an enzyme, involved in the detoxification of drugs and carcinogens. It has been
      implicated both in drug resistance and malignant transformation of epithelium.
      Using an indirect immunohistochemical technique, we have evaluated cytoplasmic
      and nuclear staining in normal urothelium, 23 superficial bladder tumours and 26
      invasive tumours. All 26 invasive tumours had been treated with platinum-based
      chemotherapy. Cytoplasmic staining was seen in normal urothelium and all bladder
      tumours. Nuclear staining was seen in 1 superficial tumour and in 13 invasive
      tumours. There was no association between nuclear staining and response to
      chemotherapy. Nuclear staining was seen in 1 area of dysplasia and in 2 of 3
      areas of carcinoma in situ. GST pi expression is not a predictor of response to
      chemotherapy. Increased intra-nuclear expression of GST pi may be associated with
      progression of transitional cell carcinoma of the bladder.

PMID- 8281407
TI  - Intravesical Bacillus Calmette-Guerin with the Danish strain for treatment of
      carcinoma in situ of the bladder.
AB  - We report our experience of the treatment of carcinoma in situ (CIS) using
      intravesical therapy with the Danish Bacillus Calmette-Guerin (BCG) strain 331
      (SSI). Forty-two patients received treatment, 11 had primary and 31 secondary
      CIS. The median follow-up period was 26 months (range 3-68). Patients received 6
      weekly instillations (1 course) and non-responders an additional 6 instillations
      at 2-week intervals (2 courses). The complete response rate was 59% for 1-course
      patients, 33% for the 2-course patients and 68% for the entire series. Patients
      were considered treatment failures if they suffered progression to invasive
      cancer, metastasis or died from transitional cell carcinoma. BCG treatment was
      more effective in primary than in secondary CIS, with a complete response rate of
      80% versus 65% and with no failures versus 35%. Patients with persistent CIS
      after the first course of BCG had a greater risk of failure than responders: 50%
      versus 17%. Patients with persistent CIS after the second course had a 75%
      failure rate. This suggests that cystectomy should be considered for non
      responders following a 6-week course and recommended to those not responding to 2
      courses. Ten patients had CIS in the prostatic urethra. All responded to BCG
      treatment; 2 suffered from recurrent CIS 1 associated with invasive urethral
      tumour. The incidence and severity of side effects were similar to those reported
      with other strains of BCG. One patient with primary CIS failed to complete the
      treatment owing to "BCG-itis".

PMID- 8281408
TI  - Transitional cell carcinoma of the bladder in young adults.
AB  - A retrospective survey of young servicemen presenting with transitional cell
      carcinoma of the bladder aged 40 years or below is presented, 19 such patients
      having been identified over a 20-year period. The results were compared with
      those of other similar series. The tumour behaviour appears to vary with age at
      presentation, its propensity for multifocal presentation, recurrence, progression
      to invasion and mortality all rising over the first 4 decades of life. These
      trends appear to be linked to grade and stage at presentation, and also tend to
      rise with age rather than altered tumour behaviour. The follow-up of young adults
      should thus be the same as for older patients presenting with the same grade and
      stage tumours.

PMID- 8281409
TI  - Salvage cystectomy after radical irradiation for bladder cancer-prognostic
      factors and complications.
AB  - We have studied 46 patients who underwent salvage cystectomy between March 1981
      and June 1992 for persistent or recurrent carcinoma after radical irradiation for
      bladder carcinoma. The overall 5-year survival rate was 43%. There was a higher 5
      year survival rate in patients with an incomplete response compared with those
      with a complete response to their prior irradiation (50 and 36%), in patients
      with grades 1 or 2 compared with grade 3 histology (75 and 28%), and in patients
      with T1 or T2 tumours compared with T3 tumours (59 and 32%). The median interval
      between commencing irradiation and performing cystectomy was 11 months. In the 25
      patients with a prior complete response the median interval was 16 months; this
      was statistically significantly longer than in the 21 patients with an incomplete
      response (median interval 7 months). A worsening of tumour grade and category was
      found in some patients when comparing the findings at cystectomy with those prior
      to irradiation. This was consistently higher in patients with a prior complete
      response than in those with an incomplete response. There were 3 deaths and 12
      non-fatal major complications due to the prior irradiation or surgery, with a
      mortality rate of 7% and an overall 5-year complications rate of 35%. Only one of
      the complications occurred in the 13 patients treated with conventional 2 Gy
      fractions alone (5 fractions/week). Their overall complication rate was
      statistically significantly lower than that of the others. Salvage cystectomy is
      indicated for selected patients with persistent or recurrent disease after
      radical irradiation for bladder cancer. The expectation of a survival rate
      similar to that found in patients treated with immediate cystectomy may not be
      justified.

PMID- 8281410
TI  - Ethanol monitoring of extravascular absorption of irrigating fluid.
AB  - Ethanol monitoring is a method for the early detection of fluid absorption by the
      intravascular route during transurethral prostatic resection. An analysis was
      made to determine whether ethanol detection could also be used to quantify
      extravascular absorption. The concentration-time profile of ethanol in the breath
      was analysed in 13 men aged between 57 and 80 years with extravasation of 860 to
      3600 ml of an irrigant containing glycine 1.5% and ethanol 1%. The results showed
      that the volume of irrigant absorbed could be predicted from the persistently
      elevated breath ethanol level at the end of surgery. This prediction had a median
      deviation of 22% from the value obtained by careful volumetric measurement.

PMID- 8281411
TI  - Complications of ultrasound-guided transperineal prostate biopsy. A prospective
      study.
AB  - A prospective study of the complications of transperineal prostate biopsy was
      undertaken in 171 patients; 150 (88%) returned a questionnaire 1 week after
      biopsy. The incidence of serious complications was low, with 1 patient requiring
      admission for presumed septicaemia and another developing acute retention of
      urine. Many patients had minor complications, with 42% having haematuria, 13%
      haemospermia and 31% pain. Only 18% needed analgesia following biopsy. Since
      transperineal prostate biopsy has such a low incidence of infective
      complications, we suggest that it should be considered in frail or elderly
      patients in whom septicaemia may be especially hazardous.

PMID- 8281412
TI  - p53 expression and clinical outcome in prostate cancer.
AB  - Abnormally high levels of expression of p53 protein are found in many human
      cancers. In most cases increased expression is associated with point mutations in
      one allele of the p53 gene and loss of the other allele. Accumulation of the
      protein product can be detected by immunohistochemistry. p53 protein expression
      in 68 men with prostate cancer, followed up for at least 8 years or until death,
      was assessed by immunohistochemistry. The aim of the study was to determine the
      association between p53 protein expression, cell cycling and clinical outcome.
      Nine (13%) of 68 tumours stained positively for p53; all 9 tumours were category
      T3 or T4. p53 positive tumours had a significantly greater Gleason score than p53
      negative tumours. Eight of the 9 p53 positive tumours had > 10% cells in G2 +
      mitosis, compared with 61% of p53 negative tumours. All 17 patients with p53
      positive tumours available for follow-up progressed clinically, compared with 28
      of 38 patients (74%) with p53 negative tumours. The median time to progression
      was 12 months in p53 positive tumours and 24 months in p53 negative tumours.
      Median survival in p53 positive tumours was 40 months, compared with 76 months in
      p53 negative tumours. This study demonstrates that overexpression of p53 in a
      small population of prostate cancers is associated with a poor prognosis in terms
      of progression and survival.

PMID- 8281413
TI  - Long-term results of combined interstitial gold seed implantation plus external
      beam irradiation in localised carcinoma of the prostate.
AB  - Carcinoma of the prostate is one of the leading causes of death in men. Patients
      with localised disease can be treated with radiotherapy, but controversy still
      exists regarding the most effective therapeutic technique. We report 180 patients
      with surgical stage A2-C prostate cancer treated between 1976 and 1986 by pelvic
      lymphadenectomy and radioactive gold seed implantation followed by external
      irradiation. Annual post-treatment biopsies were performed up to 5 years in most
      patients. Regular follow-up included a digital rectal examination, prostatic acid
      phosphatase and bone scan. One hundred and sixty-four patients had complete
      follow-up data at the end-point of data collection (December 1991). The actuarial
      10-year cancer-free survival rates were 83.0% and 91.3% for stages A2 and B1
      respectively. The incidence of positive biopsy at 2 and 5 years was 13% and 17.1%
      respectively for the whole series. A firm correlation was defined between biopsy
      result and subsequent development of local progression, distant metastases and
      overall survival. Combined interstitial gold seed implantation plus external beam
      irradiation represent a valid option for the treatment of patients with localised
      prostatic cancer.

PMID- 8281414
TI  - Comparison of laparoscopic and open ligation of the testicular vein.
AB  - Scrotal varicoceles undoubtedly contribute to subfertility in an as yet undefined
      group of patients. The best method of treatment of varicoceles, however, remains
      controversial. Laparoscopic testicular vein ligation has recently been offered as
      a new option. We examined the feasibility of laparoscopic testicular vein
      ligation (n = 11) compared with standard high ligation (n = 11). The mean post
      operative stay in the open group was 25.6 h compared with 7.1 h in the
      laparoscopic group. Analgesic requirements were a mean of 4.73 Co-proxamol
      tablets for the open group and 0.18 tablets for the laparoscopic group. All
      operations were successful. Laparoscopic ligation of the testicular vein is an
      effective treatment of varicocele with decreased post-operative morbidity.

PMID- 8281415
TI  - Dynamic echography of the penis in the follow-up of impotent patients treated
      with intracavernous injections.
AB  - Dynamic echography of the penis (DEP) after pharmacological stimulation of
      erection has been designed to evaluate the albugineal wall thickness (AWT), the
      cavernosal appearance in the normal penis and corporeal changes in patients
      treated with intracavernous injections presenting with haematomata, hyperechoic
      images, prolonged erection and Peyronie's disease. DEP was performed in 973
      patients who had had an average number of 89 (+/- 16) intracavernous injections
      for 16.7 +/- 11.7 months. A total of 1424 DEP examinations were performed.
      Transducer positioning, erectile condition, clinical recording and computer
      retrieval methods were adapted to gather ultrasonography data. The standard
      average AWTs recorded in patients free from Peyronie's disease and who were
      untreated were 0.11 cm at the septum, 0.17 and 0.15 cm at the dorsal root and the
      tip of the albuginea respectively, 0.14 cm ventrally and the diameter of the
      corpus cavernosum averaged 1.61 cm. Intracavernous therapy brought an increase in
      AWT of 15.38% to the septum, 11.76% and 10.53% to the dorsal tip and root
      respectively and 12.5% ventrally. Frequent haematomata induced greater increase,
      while prolonged erections did not. Patients with untreated Peyronie's disease
      were found to have greater AWT which decreased after treatment with
      intracavernosal injections. Before treatment abnormal penile hyperechoic images
      were found in 3.18% (intracavernous images) and 3.31% (albugineal nodules) of
      DEP, and in 7.09% and 7.54% respectively post-treatment.

PMID- 8281416
TI  - Correlation between the extent of nodal involvement and survival following groin
      dissection for carcinoma of the penis.
AB  - Between 1962 and 1986, 208 inguinal and 143 ilio-inguinal lymphadenectomies were
      performed on 201 patients with carcinoma of the penis. The crude 5-year survival
      rate was 95% for patients with negative nodes, 76% when only inguinal nodes were
      positive, and 0% when the pelvic nodes were positive. The adverse prognostic
      factors were (1) involvement of > 3 inguinal nodes, (2) perinodal infiltration in
      the inguinal area, and (3) pelvic node involvement.

PMID- 8281417
TI  - Effects of plasma exchange on sperm antibody levels in males with subfertility.
AB  - Three men with subfertility secondary to sperm antibodies with measurable serum
      sperm antibody levels underwent a course of 3 plasma exchanges over a period of 1
      week. The levels of serum anti-sperm antibodies fell by a mean of 3.3 dilutions.
      This fall was maintained for approximately 4 weeks, after which there was a
      return to the original levels. Plasma exchange is time-consuming and relatively
      expensive but it offers a possible alternative to steroid treatment (with its
      potential side effects) in men with sperm antibodies and warrants further
      investigation.

PMID- 8281418
TI  - Primary obstructed megaureter in neonates. Treatment by temporary uretero
      cutaneostomy.
AB  - During the last 10 years we have treated 24 newborn and young infants (27
      ureters) in whom the diagnosis of primary obstructed megaureter was established
      by diuresis-enhanced radionuclide renography and/or by antegrade pressure flow
      studies (Whitaker test). Temporary uretero-cutaneostomy was performed immediately
      after diagnosis. After 1 year a second modified Whitaker test showed normal
      passage of the contrast medium into the bladder in 23 ureters. In only 4 ureters
      did obstruction persist and uretero-cystoneostomy was performed.
      Ureterocystoneostomy was also performed on 8 ureters without obstruction but with
      persistent vesicoureteric reflux, ectopic ureter or diverticula. In 11 patients a
      temporary uretero-cutaneostomy was closed without corrective surgery at the
      vesicoureteric junction. Temporary uretero-cutaneostomy is a safe and effective
      therapy in primary obstructed megaureter in newborns. Spontaneous relief of
      obstruction appears to be possible in primary obstructed megaureter.

PMID- 8281419
TI  - Transtrigonal approach for excision of mullerian duct structures.
AB  - Persistent mullerian structures attached to the prostatic urethra in the male may
      cause urinary incontinence and infection. The transtrigonal technique allows
      complete excision with preservation of normal bladder function and control. We
      describe the operative technique in detail.

PMID- 8281420
TI  - 6-[18F]fluoro-L-dihydroxyphenylalanine metabolism and positron emission
      tomography after catechol-O-methyltransferase inhibition in normal and
      hemiparkinsonian monkeys.
AB  - Increased and sustained central delivery of L-dihydroxyphenylalanine (L-DOPA) is
      a desirable therapeutic strategy in Parkinson's disease. We investigated the
      effects of peripheral catechol-O-methyltransferase (COMT) inhibition, by the non
      toxic drug nitecapone on the metabolism of 6-[18F]fluoro-L-dihydroxyphenylalanine
      (6FD) and on its positron emission tomography (PET) imaging in non-human
      primates. Nitecapone produced a dose-dependent inhibition in the formation of 3-O
      methyl-6-[18F]fluorodihydroxyphenylalanine (OMFD). This inhibition of OMFD
      formation was attended by increased production of other metabolites, in
      particular 6-[18F]fluorodopamine (6FDA), 6-[18F]fluorodihydroxyphenylacetic acid
      (FDOPAC), 6-[18F]fluorohomovanillic acid (FHVA) and [18F]-sulfated conjugates
      (FSC). Although nitecapone had no effect on plasma 6FD pharmacokinetics, high
      dose nitecapone increased contrast of cerebral 18F uptake and retention between
      regions with high (striatum) versus sparse (parieto-occipital lobes) dopaminergic
      innervation. 18F uptake contrast was also improved between structures known to
      possess an intermediate dopaminergic innervation, including the upper brainstem,
      frontal and temporal lobes, versus sparsely innervated regions. This increased
      contrast was secondary to decreased activity in sparsely innervated structures
      and not to increased activity in highly innervated structures. Contrast was
      correlated inversely with the plasma OMFD/6FD concentration ratio, OMFD being the
      main 6FD metabolite which can cross the blood brain barrier. We conclude that
      nitecapone is an effective inhibitor of COMT in non-human primates. This
      inhibition results in increased 6FD flux through other catabolic pathways.
      Because of decreased OMFD formation, however, COMT inhibition improves the
      specificity of 6FD-PET and facilitates in-vivo detection of a wide range of
      dopaminergic innervation densities in cerebral structures.

PMID- 8281421
TI  - NCAM immunoreactivity on mossy fibers and reactive astrocytes in the hippocampus
      of epileptic rats.
AB  - Sprouting and synaptogenesis of mossy fibers develop in adult hippocampus after
      epilepsy. In control conditions, mossy fibers constitute the main afferent
      pathway to the Ammon's horn, where they mainly innervate CA3 pyramidal cells, but
      after treatment with the convulsant agent, kainate, mossy fibers also innervate
      granule cell dendrites generating recurrent excitatory circuits which may
      contribute to the maintenance of the epileptic condition. In the present study we
      show an enhanced immunoreactivity to neural cell adhesion molecules (NCAMs), a
      family of membrane glycoproteins involved in axonal growth. NCAM immunoreactivity
      is enriched on cytoplasmic membranes of axon shafts that are likely to be mossy
      fiber collaterals. NCAM immunoreactivity was also observed on the cytoplasmic
      membranes of reactive astrocytes, at the axon-glial contacts. Our results
      therefore suggest that there is an interaction of newly developed mossy fibers
      with other fibers and glial cells. This interaction may be mediated by NCAMs.
      Taking into account the trophic properties of NCAMs we suggest that they regulate
      the sprouting, growing and synaptogenesis of mossy fibers in epileptic
      conditions.

PMID- 8281422
TI  - Cocaine's time action profile on regional cerebral blood flow in the rat.
AB  - Cocaine is a powerful psychostimulant the high abuse liability of which in man
      appears to be linked, at least in part, to its pharmacokinetic properties. For
      example, intravenous and inhalation routes of administration result in
      appreciably higher level of dependence than either the oral or intranasal route,
      while cocaine's behavioral and physiologic profile is both route- and time
      dependent. Therefore, to determine if various aspects of the drug's profile of
      effects are due to alterations in regional neuronal activity, we measured the
      effects of cocaine on regional cerebral blood flow (rCBF) 1, 2, 5, 15 and 45 min
      after a single 1.0 mg/kg i.v. cocaine injection. rCBF is known to directly
      reflect the state of local neuronal activity and, when measured
      autoradiographically using the method of Sakurada et al., can be resolved with a
      very high temporal resolution (30 s). A heterogeneous pattern of cerebral
      activation was seen. Of those regions which responded to cocaine, all but three
      did so with a threshold to effect of less than 1 min. Several groups of
      structures were evident: (1) those regions where blood flow returned to baseline
      prior to the 5 min measurement group (including several amygdaloid nuclei and
      lateral septum); (2) those returning to baseline prior to the 15 min sacrifice
      point (including limbic cortex); (3) regions activated for at least 15 but less
      than 45 min (including such motor-related regions as the caudate, substantia
      nigra and globus pallidus); and (4) those demonstrating persistent rCBF
      alterations for the entire 45 min observation period (including nucleus
      accumbens, olfactory tubercle, hippocampus, various thalamic nuclei and medial
      prefrontal cortex). It thus appears that cocaine's duration of action varies
      heterogenously across both time and brain structure, with many limbic regions
      displaying either very brief or prolonged duration of action while many motor
      related structures display intermediate times of action. This regionally distinct
      time-course may reflect the diverse behavioral profile seen after cocaine
      administration in the rat.

PMID- 8281423
TI  - Australian funnel-web spider toxin, versutoxin, enhances spontaneous synaptic
      activity in single brain neurons in vitro.
AB  - Neurotoxins isolated from the venoms of Australian funnel-web spiders increase
      spontaneous action potential activity in a variety of excitable cells. In the
      present study intracellular recordings were made with microelectrodes (30-60 M
      omega, 2 M KCl) from locus coeruleus, mesencephalic nucleus of the trigeminal
      nerve and laterodorsal tegmental neurons in brain slices. Versutoxin, a
      polypeptide toxin isolated from the venom of Hadronyche versutus produced a
      profound increase in spontaneous synaptic activity impinging on neurons, which
      did not fully recover for up to 3 h after washout. The threshold concentration
      was 1.5 nM in locus coeruleus neurons, with increasing concentrations (up to 50
      nM) producing larger effects. A modest increase in synaptic activity was observed
      in mesencephalic nucleus of the trigeminal nerve neurons during superfusion with
      50 nM versutoxin. The increase in spontaneous synaptic activity was reversed by
      agents which block synaptic potentials impinging on locus coeruleus neurons,
      i.e., tetrodotoxin (100 nM), Co2+ (3 mM) or the combination of 6-cyano-7
      nitroquinoxaline-2,3-dione (10 microM) and bicuculline (30 microM). Threshold,
      peak amplitude, maximum rate of rise, duration, amplitude of
      afterhyperpolarisations and interspike intervals of action potentials in each
      type of neuron were unaffected by versutoxin. Voltage-current relationships were
      also unaffected. Calcium-dependent action potentials evoked in locus coeruleus
      neurons in the presence of tetrodotoxin were unaffected by versutoxin, as were
      depolarisations produced by exogenously applied glutamate. These results suggest
      that versutoxin increases spontaneous synaptic activity, but has no effect on the
      membrane properties of the soma of several types of rat brain neurons.

PMID- 8281424
TI  - Firing patterns of nucleus accumbens neurons during cocaine self-administration
      in rats.
AB  - The firing patterns of neurons in the nucleus accumbens (NA) were recorded in
      rats trained to self-administer cocaine via response contingent intravenous drug
      infusions. Recordings were obtained from permanently implanted multiple electrode
      arrays (8 microwires) inserted bilaterally into the NA and/or ventral striatum
      (NA-VS) in animals exhibiting stable responding (inter-infusion intervals, INT)
      during test sessions consisting of 16-30 drug delivery episodes. Electronically
      isolated and identified NA-VS neurons showed distinct patterns of phasic
      increases in firing relative to the occurrence of the reinforced lever press. Two
      particular firing patterns, however, were repeatedly encountered in different
      animals. In one type, a marked increase was observed in discharge following
      response contingent drug delivery. A second firing pattern showed two distinct
      temporally separated brief firing peaks (bursts), one immediately prior to the
      initiation of responding, and the other a brief discharge commencing within 200
      ms after the initiation of drug delivery. The time between firing peaks was found
      to be modifiable by changing the response/reward (FR) ratio for drug delivery. A
      third finding was that the correlates of the self-administration response were
      not solely the result of drug infusion since, (1) phasic firing increases were
      not observed when the drug was delivered non-contingently during the same session
      and, (2) the emergence of patterns was frequently delayed within the session
      until after drug self-administration behavior stabilized at regular INTs. The
      findings are discussed in terms of the significance of NA-VS neuron firing
      correlates for the initiation and maintenance of cocaine self-administration.

PMID- 8281425
TI  - Type I corticosteroid receptors modulate PTZ-induced convulsions of withdrawal
      seizure prone mice.
AB  - Corticosteroids have been shown to modulate convulsion expression in humans and
      animals. It is hypothesized that type I corticosteroid receptors mediate the
      excitatory effects of corticosteroids in vivo based on low-dose efficacy of
      corticosterone, and differential effects of mineralocorticoids vs.
      glucocorticoids on convulsions. In the present experiments, the effects of
      altering corticosterone levels, and the role of the type I receptor in mediating
      these effects, were examined using pentylenetetrazol (PTZ)-induced convulsions in
      ethanol withdrawal seizure prone (WSP) mice. It was hypothesized that stimulation
      of type I receptors partially mediates the expression of tonic hindlimb extensor
      (THE) convulsions produced by PTZ. Aminoglutethimide, a steroid synthesis
      inhibitor, increased latencies to PTZ-induced THE. This anticonvulsant effect was
      reversed by corticosterone and the type I agonist, deoxycorticosterone (DOC), but
      not by the type II agonist, dexamethasone. Furthermore, two type I receptor
      antagonists, spironolactone and RU26752, increased latencies to PTZ-induced THE,
      suggesting that they have anticonvulsant action. In summary, the results of these
      experiments suggest that type I corticosteroid receptors are important for
      expression of PTZ-induced convulsions.

PMID- 8281426
TI  - Superfusion of verapamil on the cerebral cortex does not suppress epileptic
      discharges due to restricted diffusion (rats, in vivo).
AB  - The organic calcium channel blocker verapamil has been demonstrated to block
      epileptic activity in various experimental models both in vitro and in vivo. The
      drug, however, does not pass the blood-brain barrier, so that both the oral route
      and intravenous administration of the drug are ruled out for antiepileptic
      treatment. The present investigations analyzed the effects of verapamil applied
      epicortically in experimental models of interictal penicillin-induced and ictal
      pentylenetetrazol-induced epileptic activity in rats. Such epicortical
      application of verapamil was ineffective in suppressing either interictal or
      ictal epileptic activity. To test whether this lack of effect was due to poor
      penetration of the substance into the cortical tissue, the diffusion
      characteristics of verapamil were studied in agar and in gray matter by pressure
      microejection and an appropriate verapamil-selective microelectrode. The
      diffusion could be described fully by a diffusion coefficient D (5.08 x 10(-6)
      cm2 x s-1), tortuosity lambda (1.51) and concentration-dependent uptake, k' (2.23
      x 10(-3) s-1). Using these values, the depth-dependent concentration gradient
      resulting from superfusion of the substance was calculated for agar and brain. In
      concentration measurements done in brain tissue, however, verapamil could not be
      detected in cortical layers deeper than 150 microns, which did not agree with the
      theoretical prediction. This observation may indicate a diffusion barrier at the
      interface between superfusing fluid and tissue. The results indicate that
      epicortical administration of verapamil is not efficacious in treatment of
      epilepsy.

PMID- 8281427
TI  - Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal
      dopamine content in unilateral 6-hydroxydopamine lesioned rats.
AB  - In the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's
      disease, controversy exists concerning the use of apomorphine- or D-amphetamine
      induced rotations as reliable indicators of nigrostriatal dopamine depletion. Our
      objective was to evaluate which, if either, drug-induced behavior is more
      predictive of the extent of nigrostriatal dopamine depletion. Fischer 344 and
      Sprague-Dawley rats were unilaterally injected with 9 micrograms/4 microliters/4
      min 6-hydroxydopamine into the medial forebrain bundle. The animals were
      behaviorally tested with apomorphine (0.05 mg/kg, s.c.) and D-amphetamine (5.0
      mg/kg, s.c.). Following testing, the brains were removed and the right and left
      striata, substantia nigra and ventral tegmental area were dissected free and
      quickly frozen at -70 degrees C for analysis of catecholamine content by high
      performance liquid chromatography coupled with electrochemical detection. Our
      results indicate that an animal which has greater than a 90% depletion of
      dopamine in the striatum might not rotate substantially on apomorphine, without a
      concomitant depletion of > 50% of the DA content in the corresponding substantia
      nigra. No correlations were seen involving depletions of the ventral tegmental
      area and the extent of the lesions to the striatum. Submaximally lesioned (75-90%
      depleted) rats were found to rotate on D-amphetamine but not on apomorphine. In
      addition, control rats that did not receive lesions were often seen to rotate
      extensively on D-amphetamine. We therefore conclude that maximal lesions of the
      striatum and substantia nigra are required to generate rotations demonstrable
      with low dose apomorphine but not with D-amphetamine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8281428
TI  - Desmethylimipramine, a potent inhibitor of synaptosomal norepinephrine uptake,
      has diverse effects on thyroid hormone processing in rat brain. I. Effects on in
      vivo uptake of 125I-labeled thyroid hormones in rat brain.
AB  - Several lines of evidence point to an interaction between amine uptake inhibitors
      (tricyclic antidepressants) and thyroid hormones. To examine this issue under
      conditions which would minimize secondary effects of drug treatment,
      desmethylimipramine (DMI), a highly specific norepinephrine uptake inhibitor, was
      given acutely as a single i.p. dose one hour before i.v. [125I]triiodothyronine
      (T3*) or [125I]thyroxine (T4*). Tissues were analysed after rat decapitation at
      3, 5, 10, and 20 min intervals thereafter. DMI had a small but significant
      inhibitory effect on the brain uptake of both T3* (7.4%) and T4* (19%) over their
      respective 20-min time courses as indicated by two-way ANOVA. To examine the drug
      response further and to determine the effect of thyroid status on the response,
      hypothyroid (HYPO) and T4-induced hyperthyroid (HYPER) rats, were given i.v. T3*
      and, 5 min later, i.p. DMI or saline. They were killed 3 h later and tissue
      analysed. Because DMI effects on T4* uptake could not be evaluated over a 3 h
      period without blocking T4* to T3* conversion, sodium ipodate (60 mg/kg) was
      given in 2 doses before i.v. T4*. Under these conditions, DMI significantly
      reduced brain concentrations of the administered T3* and T4* in HYPO (15% and
      19%) and in HYPER rats (13% and 25%). These results suggest that, as it does in
      the case of norepinephrine, DMI blocks the uptake site for T3 and T4 in rat
      brain. No information is available regarding the relationship, if any, between
      the thyroid hormone and norepinephrine uptake sites.

PMID- 8281429
TI  - Modulation of high-affinity choline carrier activity following incubation of rat
      hippocampal synaptosomes with hemicholinium-3.
AB  - Membrane carriers display structural and functional asymmetry with a substrate
      binding site which can be oriented alternately, but not simultaneously, to the
      extracellular and intracellular environment. Hemicholinium-3 is an inhibitor of
      the high-affinity choline carrier in cholinergic nerve terminals which binds to
      the transporter at the outer membrane surface but is not taken up into the cell.
      In the present study, we investigated the decline in choline transport which
      occurs during the first few minutes cholinergic nerve terminals are incubated in
      physiological salt solutions. Following incubation of rat hippocampal
      synaptosomes with hemicholinium-3, samples were washed free of the inhibitor and
      high-affinity choline uptake was measured. Choline uptake into hemicholinium
      treated nerve terminals was significantly greater than control (132 +/- 4%). This
      effect appeared not to be due to an increase in uptake of choline above initial
      values in the hemicholinium-treated synaptosomes, but to a decrease in choline
      carrier activity in control samples by more than 25% during the first few minutes
      of incubation. Addition of hemicholinium-3 to samples after the preincubation
      induced decrease in choline uptake, followed by a wash period to remove the
      inhibitor resulted in elevation of choline uptake levels to initial levels. The
      effect of hemicholinium-3 was concentration-dependent, requiring near saturating
      concentrations of the inhibitor to elicit the effect. Measurement of
      acetylcholine content of synaptosomes at different points during the incubation
      procedure revealed that there was a trend for transmitter levels to vary
      inversely compared to choline uptake activity, but the differences were not
      statistically significant during treatments when significant changes in transport
      activity were measured.

PMID- 8281430
TI  - Dynamics of electroencephalographic sleep spindles and slow wave activity in men:
      effect of sleep deprivation.
AB  - Recent developments in the understanding of the neurophysiological mechanisms
      underlying electroencephalographic (EEG) slow waves and sleep spindles imply an
      inverse relationship between these two EEG activities. The interrelationship
      between slow wave activity (0.75-4.5 Hz) and sleep-spindle activity (12-15 Hz) in
      electroencephalograms recorded in nine male subjects, during nocturnal baseline
      sleep and during recovery sleep from 40 h of wakefulness, was analyzed by power
      spectral analysis based on the fast Fourier transform and by transient patterns
      detection algorithms. Both techniques revealed that spindle activity was highest
      in sleep stage 2, increased over consecutive non-rapid-eye-movement sleep (non
      REM sleep) episodes and was suppressed during recovery sleep. In contrast, slow
      wave activity decreased over consecutive non-REM sleep episodes and was enhanced
      during recovery sleep. Analysis of the dynamics of spindle and slow-wave activity
      within non-REM sleep episodes demonstrated that in the initial 20% of these
      episodes both spindle activity and slow wave activity increased, whereafter slow
      wave activity continued to increase but the average amplitude of spindles and
      total spindle activity, but not spindle density, decreased. At the end of non-REM
      sleep episodes the reverse pattern was observed. Sleep deprivation induced a more
      rapid rise of both spindle and slow wave activity in the very beginning of sleep.
      These data demonstrate that when averaged per sleep episode or non-REM sleep
      episode an inverse relationship between SWA and spindle activity exists but that
      in the initial and final part of non-REM sleep episodes the association between
      these two activities is positive. This biphasic relationship is discussed with
      reference to the hypothesis that the transition from sleep spindles to slow waves
      is dependent on a progressive hyperpolarization of thalamo-cortical neurons.

PMID- 8281431
TI  - Localisation of functional muscarinic receptors in the rat cochlea: evidence for
      efferent presynaptic autoreceptors.
AB  - In the rat cochlea, the activation of muscarinic receptors stimulates the
      hydrolysis of phosphoinositides but the importance of this muscarinic effect is
      still unknown. In order to find out about the role of the muscarinic receptors in
      the cochlea, we examined their functional distribution within this organ. This
      was achieved by measuring the formation of [3H]inositol phosphates induced by
      carbachol (1 mM) in two regions of the cochlea: the modiolus and the organ of
      Corti. At both sites, carbachol enhanced the accumulation of inositol phosphates
      in an atropine-sensitive way. These stimulations were completely antagonised by 4
      diphenylacetoxy-N-methyl piperidine methiodide (1 microM) but unchanged by
      pirenzepine (1 microM). In cochleas depleted of outer hair cells by a treatment
      with amikacin, the carbachol-induced formation of inositol phosphates is not
      altered with respect to control, undamaged cochleas. Conversely, when the medial
      cholinergic axons which form synapses with the outer hair cells are destroyed by
      the section of the crossed olivocochlear bundle the carbachol-stimulated inositol
      phosphates response is reduced by 35% in the organ of Corti. This section has no
      effect in the modiolus, despite the degeneration of some modiolar fibers. Our
      results show that functional muscarinic receptors are distributed both in the
      organ of Corti and in the modiolus. These two structures contain presumably the
      same class of cholinoceptor. The effects of selective destruction clearly
      demonstrate that a population of muscarinic receptors is located on presynaptic
      membranes at the level of the medial axon-outer hair cell contacts. They also
      point to spiral ganglion neurons and/or the Schwann cells as sites for the
      functional cholinoceptors in the modiolus.

PMID- 8281432
TI  - Effects of norepinephrine on [3H]dopamine release and horizontal cell receptive
      field size in the goldfish retina.
AB  - Norepinephrine increased the release of pre-loaded [3H]dopamine from goldfish
      retinas. Pharmacological studies suggested that the norepinephrine-induced
      [3H]dopamine release was due to an exchange mechanism between norepinephrine and
      pre-loaded [3H]dopamine. Norepinephrine also depolarized and reduced the
      receptive-field size of horizontal cells in goldfish retinas. The action of
      norepinephrine on horizontal cells was probably not due to the release of
      endogenous dopamine because the effect of norepinephrine was not abolished in
      retinas in which all dopaminergic neurons had been destroyed by prior treatment
      with 6-hydroxydopamine. The pharmacology of the effect of norepinephrine on
      horizontal cells suggested that it was due to an agonist action of norepinephrine
      acting at horizontal cell dopamine receptors. It is still unclear whether
      endogenous norepinephrine is a regulator of dopamine release in the fish retina.
      Consequently, the function of the putative norepinephrine-containing amacrine
      cells of the fish retina remains to be elucidated.

PMID- 8281433
TI  - The delta-opioid signal transduction on the gonadotropin-releasing hormone
      release is eicosanoid dependent.
AB  - In static incubations, the K+ induced release of gonadotropin-releasing hormone
      (GnRH) and of prostaglandin (PG) E2, was 2-3 times higher in the isolated median
      eminence (ME) compared to the hypothalamic area containing the arcuate nucleus
      (ARN) plus the ME. The delta-opioid agonist DTLET, induced a parallel, dose
      dependent reduction of GnRH and PGE2 release in the ARN plus ME. Both effects of
      DTLET were blocked by the delta-opioid antagonist Diallyl-G. In the isolated ME,
      DTLET reduced the secretion of PGE2 but enhanced the release of GnRH. In this
      area Diallyl-G had no effect on the PGE2 release but blocked the GnRH secretion.
      When the PGE2 production was blocked by indomethacin in the ARN plus ME
      preparation, DTLET increased the release of GnRH and induced the production of
      leukotrienes (LTs). On the other hand, DTLET decreased the release of both GnRH
      and PGE2 in the presence of nordihydroguaiaretic acid (NDGA), an inhibitor of the
      production of LTs. The above results suggest that: (a) the delta-opioid agonist
      DTLET modulates GnRH release differentially in the hypothalamic areas examined;
      and (b) the arachidonic acid metabolites are involved in the mode of action of
      DTLET on the release of GnRH in the ARN plus ME hypothalamic fragment.

PMID- 8281434
TI  - Effects of recurrent collateral inhibition on Purkinje cell activity in the
      immature rat cerebellar cortex--an in vivo electrophysiological study.
AB  - We present here a study on the effects of inhibitory recurrent collaterals of
      Purkinje cell (PC) axons on the activity of the immature rat cerebellar cortex.
      Simultaneous extracellular recordings of pairs of PCs were performed in rat pups
      aged 5-8 days postnatal. Bicuculline was applied to the surface of the cortex in
      order to functionally antagonize PC recurrent collaterals. At this early
      developmental stage these are the only inhibitory links in the network. Dye marks
      from the microelectrode tips and 3D serial-section reconstruction of the
      structure allowed the exact determination of the distance separating recorded
      cells and of their respective orientation in the cortex. Standard statistical
      tests and an informational entropy index were used to calculate levels of
      cooperativity. By comparing PC activity under control conditions and after
      bicuculline superfusion it is shown that recurrent collateral inhibition has a
      structurating effect on the PC activity and that it increases the informational
      content of the network. Inhibition decreases the activity of the cells by 35% and
      drastically changes the interspike interval histograms. This leads to a more
      constrained state of the system. Three types of coupling via recurrent
      collaterals are present: symmetrical, asymmetrical or non existent. The exact
      type of coupling follows a simple vicinity rule and strongly influences the
      cooperativity level between the recorded cells. This cooperativity was also found
      to be spatially compartmentalized. Several pairs were driven by common inputs via
      climbing fibers or parallel fibers. Using the predictive value of a theoretical
      model of this immature structure we propose a complementary explanation of the
      role of the recurrent collaterals at this stage of development: that of a spatial
      and temporal filter, specific to each different microzone.

PMID- 8281435
TI  - Autoradiographic distribution of glutamatergic ligand binding sites in Xenopus
      brain: evidence for intracellular [3H]AMPA binding sites.
AB  - The binding of a series of [3H]glutamatergic ligands was determined by receptor
      autoradiography of membrane homogenate pellets and horizontal sections of Xenopus
      brain. Consistent with previous reports that a 'unitary' glutamate receptor is
      present in Xenopus CNS, the radioligands showed similar densities of binding
      sites in the membrane homogenate pellets. Furthermore, [3H]kainate binding was
      completely displaced by AMPA or CNQX, [3H]AMPA binding was completely displaced
      by kainate or CNQX and [3H]CNQX binding was completely displaced by AMPA or
      kainate. However, in whole brain sections there were apparently 2- to 5-fold more
      [3H]AMPA and [3H]CNQX than [3H]kainate sites. The absence of these extra sites in
      broken-washed membrane preparations suggests that the additional [3H]AMPA and
      [3H]CNQX binding may be due to cytosolic sites. The observation that all [3H]AMPA
      and [3H]CNQX binding in the brain sections is displaced by kainate indicates that
      the putative cytosolic sites are sensitive to relatively high concentrations of
      kainate but that they differ from the previously characterised Xenopus CNS
      unitary receptors.

PMID- 8281436
TI  - In vitro reinforcement of hippocampal bursting by the cannabinoid receptor
      agonist (-)-CP-55,940.
AB  - Involvement of cannabinoid receptors in behavioral reinforcement is suggested by
      widespread human use of marihuana, although animal tests of cannabinoid
      reinforcement have produced mixed results. Cannabinoid receptors are found in
      high density in rat hippocampus and other brain areas. Using the hippocampal
      slice preparation, we attempted to demonstrate in vitro reinforcement of CA1
      bursting with local micropressure applications of the high-affinity synthetic
      cannabinoid receptor agonist (-)-CP-55,940. Approximately 60% of the tested
      neurons showed increased burst activity after a series of brief, burst-contingent
      applications of (-)-CP-55,940 at pipette concentrations of 5 and 10 microM.
      Identical microinjections of (-)-CP-55,940 administered independently of cellular
      activity did not increase and usually suppressed hippocampal bursting. Since
      general stimulation of CA1 activity by (-)-CP-55,940 can thus be ruled out, we
      conclude that burst-contingent applications of a cannabinoid receptor agonist can
      reinforce hippocampal firing in vitro.

PMID- 8281437
TI  - Enhancement of murine gustatory neural responses to D-amino acids by saccharin.
AB  - Taste enhancing effects of sodium saccharin (Sac) on responses to particular
      sweet-tasting D-amino acids were found during the recording of mouse chorda
      tympani nerve responses to various taste stimuli in C57BL and BALB strains. In
      both strains, responses to D-tryptophan and D-histidine significantly increased
      (167.7-216.7% of control) after the stimulation with Sac as compared with those
      applied before Sac. In C57BL mice, the enhancement of Sac was also observed in
      response to D-phenylalanine (262.5% of control), but this was not the case for
      BALB mice, suggesting a prominent strain difference in response to D
      phenylalanine, as shown previously. Responses to other sweet-tasting D- and L
      amino acids and sugars were not enhanced by Sac. Enhancement of responses to
      these D-amino acids by Sac was also evident when responses to a mixture of D
      amino acids and Sac were compared with the sum of responses to each component,
      although in this response analysis, the calculated magnitude of enhancement
      generally become smaller (135.7-180.5% of the sum) and enhancement of D-histidine
      responses disappeared. Except for Sac, various sweet-tasting amino acids and
      sugars and NaCl also tested showed no enhancing effect on D-phenylalanine
      responses in C57BL mice. Sac and D-amino acids, to which responses were enhanced
      by Sac, possess some common molecular features, namely ring structures. This
      structural similarity probably relates to the occurrence of the enhancement at
      the receptor sites.

PMID- 8281438
TI  - Cardiac output and regional hemodynamics during recurrent seizures in rats.
AB  - Altered cardiovascular function in status epilepticus may contribute to mortality
      and morbidity in patients. We investigated changes in cardiac output and regional
      hemodynamics during 2 h of recurrent PTZ-induced seizures in anesthetized,
      paralyzed rats using radioactive microspheres, thermodilution methods, and the
      pulsed Doppler technique. Cardiac output fell 30-60% during recurrent seizures in
      17 of 27 animals. The fall in cardiac output was sudden in onset and occurred
      primarily in association with seizures accompanied by prolonged increases in MABP
      but no change in central venous pressure. Total peripheral resistance (TPR) rose
      during early seizures in association with vasoconstriction of renal and certain
      splanchnic vascular beds. Ictal increases in TPR became attenuated during late
      seizures, due to failure of renal and splanchnic beds to constrict. Therefore,
      derangements in both cardiac and vascular function occur during late seizures.
      These derangements may contribute to both cerebral hypoperfusion and sudden death
      in status epilepticus.

PMID- 8281439
TI  - Conformationally restricted sumatriptan analogues, CP-122,288 and CP-122,638
      exhibit enhanced potency against neurogenic inflammation in dura mater.
AB  - CP-122,288 and CP-122,638 blocked plasma protein extravasation response within
      dura mater following trigeminal ganglion stimulation. The threshold (1 and 0.1
      pmol/kg, respectively) was remarkably lower than for sumatriptan (7 nmol/kg), as
      was the dose at maximum response. As with sumatriptan, substance P-induced plasma
      leakage was unaffected by either compound, and metergoline only partially (27%)
      reversed the effects of CP-122,288. The data suggest the importance of
      modifications at the aminoethyl side chain to the actions of sumatriptan and
      possibly to the treatment of migraine headache.

PMID- 8281440
TI  - Decarboxylation of L-dopa by cultured mouse astrocytes.
AB  - Cultured astrocytes contain immunologically specific aromatic L-amino acid
      decarboxylase (AADC) protein and express the AADC gene. Following incubation with
      L-Dopa, glial cultures synthesize and metabolize dopamine. The addition of
      pyridoxal 5-phosphate did not change the rate of dopamine synthesis. The
      formation of dopamine was blocked by NSD-1015. These experiments show that mouse
      cultured astrocytes are capable to convert L-Dopa into dopamine in a dose
      dependent fashion.

PMID- 8281441
TI  - Complex catecholaminergic modulation of the stimulatory effect of interleukin-1
      beta on the corticotropic axis.
AB  - We recently showed that bilateral neurotoxic microlesions (6-OH-DA) of the
      ventral noradrenergic ascending bundle (VNAB-X) at stereotaxic coordinates that
      blocked corticotropic stress responses did not affect the ACTH surge after
      bilateral intra-paraventricular (i.PVN) injections of interleukin-1 beta (IL-1
      beta), and that lesioning at these stereotaxic coordinates obliterated the dorsal
      axonal populations of the VNAB (dVNAB-X), but spared the bundle's most ventral
      axons (vVNAB). The present study compares the effects of IL-1 beta given i.PVN (2
      x 5 ng) of intra-arterially (i.a.) (100 ng) on plasma ACTH in rats with bilateral
      6-OH-DA microlesions placed in the dVNAB or the vVNAB, or in an intermediary
      central position (cVNAB-X). Unlike our previous results, in which dVNAB-X did not
      alter the biphasic ACTH response to i.PVN IL-1 beta, both vVNAB-X and cVNAB-X
      reduced by 50-75% the early and delayed ACTH surges which are typical of the
      i.PVN route. On the other hand the swift monophasic ACTH surge usually occurring
      after an i.a. injection of IL-1 beta was 65% smaller after dVNAB-X, but was
      doubled after vVNAB-X or cVNAB-X. Hence, the release of ACTH after both i.PVN or
      i.a. IL-1 beta requires brainstem afferences conveyed to the hypothalamus by the
      VNAB. However, the VNAB appears to include at least two functionally different
      subsets of axons, the roles of which in the ACTH response to IL-1 beta depend on
      the route by which the cytokine is given.

PMID- 8281442
TI  - Daily variation in active glycogen phosphorylase patches in the molecular layer
      of rat dentate gyrus.
AB  - A larger number of discrete patches of active glycogen phosphorylase (alpha GP)
      were found in the molecular layer of the hippocampal dentate gyrus in rats
      sacrificed during the daily dark phase (mean = 28.7/section) than during the
      light phase (mean = 7.8/section). Light-dark differences in the patterns of alpha
      GP may reflect circadian differences in metabolic demand in the hippocampus.
      Patch sizes were consistent with increased activation of single astrocytes or
      perisynaptic astrocyte clusters by focal input at night.

PMID- 8281443
TI  - Morphine differentially modulates nociceptive input in the superficial versus the
      deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in the rat.
AB  - Morphine enhanced the noxious thermal stimulus-evoked responses in 4/13 (31%)
      selectively nocireceptive neurons in the superficial dorsal horn, inhibited the
      responses in 4/13 (31%) neurons and produced a biphasic effect in 2/13 (17%)
      neurons. Naloxone antagonized these effects in 7/7 neurons. In contrast, morphine
      produced a naloxone reversible reduction in the nociceptive responses of 4/4
      (100%) multireceptive neurons in the deeper dorsal horn of the medulla. The data
      are interpreted to indicate that opiates may differentially modulate nociceptive
      input in the superficial versus the deeper dorsal horn.

PMID- 8281444
TI  - Maintenance of a circadian phase adjustment of the human melatonin rhythm
      following artificial long days.
AB  - In winter, a 5-day exposure of 4 human subjects to a skeleton photoperiod, with 3
      h of bright light in the evening and again in the morning, phase advanced the
      morning serum melatonin offset by 1-3 h as compared with the original winter
      melatonin rhythm pattern. The phase advance persisted for 3 days even after the
      bright light withdrawal. The data indicate that the long skeleton photoperiod had
      a prevailing phase-advancing effect on the melatonin rhythm and its underlying
      pacemaker. The maintenance of the phase advance might be due to the fixed sleep
      wake schedule.

PMID- 8281445
TI  - Subthalamic nucleus lesion regularizes firing patterns in globus pallidus and
      substantia nigra pars reticulata neurons in rats.
AB  - Subthalamic nucleus lesion altered the statistical properties of the firing
      patterns of globus pallidus and substantia nigra pars reticulata neurons recorded
      in urethane anesthetized rats by increasing the proportion of cells in both
      structures that fired with a very highly regular pattern (from approximately 25%
      to approximately 50%). In all cases, the most regularly firing neurons fired at a
      higher mean rate than did more slowly firing neurons. In contrast, globus
      pallidus lesion shifted the pattern of substantia nigra neurons towards more
      irregular firing and induced a bursty pattern in two neurons.

PMID- 8281446
TI  - MK-801 inhibits the development of morphine tolerance at spinal sites.
AB  - The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 has been shown to
      attenuate tolerance development in rats. In this study, we show that MK-801
      inhibits tolerance to the antinociceptive effects of morphine, as assessed by the
      tail-flick test, in spinalized rats. These results suggest that NMDA receptor
      antagonists inhibit opiate tolerance at spinal sites, and also provide strong
      evidence that the effects of MK-801 are not due to its ability to interfere with
      associative learning, but instead to inhibition of non-associative mechanisms of
      opiate tolerance.

PMID- 8281447
TI  - Neuroprotective effect of chronic infusion of basic fibroblast growth factor on
      seizure-associated hippocampal damage.
AB  - Basic fibroblast growth factor (bFGF) has been shown to have neuroprotective
      effects in animal models of ischemia. To determine whether bFGF is protective
      against seizure-induced brain damage, we administered bFGF through osmotic pumps
      prior to, and after treatment with kainic acid (KA). Recombinant bFGF, CS23, a
      modified human bFGF, was infused into the lateral ventricles in rats for 2 days
      before and 5 days after the injection of KA. Control rats received equal volumes
      of phosphated saline over the same period of time. Infusion of 5 micrograms/ml of
      bFGF (0.5 microliter/h) did not modify the latency and duration of seizures
      induced by intraperitoneal injections of KA. However, bFGF prevented cell loss in
      the hippocampus in 80% of the rats. In control rats, cell loss in the hippocampus
      was found in all rats. These results indicate that bFGF has a substantial
      neuroprotective effect.

PMID- 8281449
TI  - An unrelayed projection of jaw-muscle spindle afferents to the cerebellum.
AB  - Jaw-muscle spindle afferents were physiologically characterized and stained with
      horseradish peroxidase. Two types of afferent responses were observed during jaw
      muscle stretches; one group showed considerable dynamic sensitivity indicative of
      primary muscle spindle afferents while the other showed little dynamic
      responsiveness indicative of secondary spindle afferents. Axon collaterals from
      both types were observed coursing within the ipsilateral superior cerebellar
      peduncle, indicating that some jaw-muscle spindle afferents project directly to
      the cerebellum without relay.

PMID- 8281448
TI  - Intra-ventromedial hypothalamic injection of cholinergic agents induces rapid
      hyperglycemia, hyperlactatemia and gluconeogenesis activation in fed, conscious
      rats.
AB  - Microinjections of carbachol (50 nmol) or neostigmine (25 nmol) in 0.5 ml saline
      into the ventromedial nucleus of the hypothalamus (VMH) (but not into the lateral
      hypothalamic area) of fed, conscious rats produced marked increases in plasma
      glucose and lactate, which were suppressed or markedly reduced by previous
      adrenodemedullation. The rate of incorporation of 14C from infused bicarbonate
      (0.60 microliter, 0.20 microCi/min), an index of gluconeogenic activity,
      increased significantly after VMH administration of neostigmine. The data suggest
      that cholinergic synapses in the VMH participate of a central glucoregulatory
      system that increases hepatic glucose production mainly through a stimulation of
      adrenal medulla epinephrine secretion.

PMID- 8281450
TI  - Neuronal induction of 72-kDa heat shock protein following methamphetamine-induced
      hyperthermia in the mouse hippocampus.
AB  - By means of an immunohistochemical technique, we examined the neuronal induction
      of 72-kDa heat shock protein (HSP72) in response to methamphetamine-induced
      hyperthermia in the mouse hippocampus. Strong HSP72 immunoreactivity (ir) was
      found in the neurons of hippocampus proper, particularly in the CA1/2 and medical
      CA3 subfields, at 10 h after drug injection. By 18 h, those neurons still
      revealed HSP72-ir, while neurons of the dentate gyrus also appeared positive for
      HSP72. At this stage, intense HSP72-ir was first detected in non-neuronal cells,
      i.e. glial and vascular endothelial cells. At 24 h, no apparent HSP72-ir was
      found in the hippocampal neurons, while only non-neuronal cells still revealed
      immunoreactivity for HSP72. In addition, no morphological evidence of cell
      degeneration or loss was noted in the CA1 sector or other hippocampal regions at
      5 days after hyperthermic insult. In conclusion, (1) methamphetamine-induced
      hyperthermia per se is a stressful stimulant causing neuronal induction of HSP72
      in the hippocampus neurons, particularly of CA1/2 and medial CA3 sectors, but
      does not prove fatal to the cells; (2) there is a cell type-specific difference
      in response to hyperthermic insult by inducing HSP72 and the timing of the
      induction response in the hippocampal formation; and (3) the animals that
      underwent drug-induced hyperthermia may be useful as an experimental model for
      the study of the protective mechanism of heat shock proteins against subsequent
      harmful stimuli.

PMID- 8281451
TI  - Brain-derived neurotrophic factor enhances function rather than survival of
      intrastriatal dopamine cell-rich grafts.
AB  - Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival
      of dopaminergic neurons from the substantia nigra in cell culture. In order to
      assess whether a similar survival-promoting effect is present also in vivo, we
      grafted fetal nigral tissue to the dopamine-depleted striatum of 6
      hydroxydopamine-lesioned rats receiving two-week intraventricular infusions or
      daily intrastriatal injections of BDNF, NGF, or vehicle. When infused chronically
      at a high dose (12 micrograms/day) into the lateral ventricle, BDNF caused a
      behavioral syndrome of reduced food and water intake, body weight loss, and
      locomotor hyperactivity in comparison to NGF- and vehicle-infused graft
      recipients. NGF-infused graft recipients displayed a transient weight loss during
      the first week of infusion. At 15 days, amphetamine-induced turning was
      significantly attenuated to 3% of pregraft values in BDNF-infused recipients,
      whereas functional graft effects were not present in NGF- or vehicle-infused
      animals. Survival of tyrosine hydroxylase-immunoreactive graft cells, however,
      was similar in all treatment groups. Notably, NGF- and BDNF-infusions led to a
      significant size increase of cholinergic host neurons in the medial septal
      nucleus and the vertical limb of the diagonal band ipsilateral to the infusion,
      whereas there was no cholinergic neuron hypertrophy in vehicle-infused animals.
      Daily intrastriatal injections of BDNF (2 micrograms) produced no weight loss or
      locomotor hyperactivity, but also enhanced functional graft effects in BDNF
      injected, as compared to vehicle-injected animals. Survival rates of grafted
      tyrosine hydroxylase-immunoreactive cells were, however, similar in both
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281452
TI  - Effect of U-50488h, a selective opioid kappa receptor agonist, on vascular injury
      after spinal cord trauma.
AB  - U-50488H, a selective opioid kappa receptor agonist has been shown to be a
      neuroprotective agent in animal models of spinal cord injury. The mechanism of
      action of U-50488H is not known. Methylprednisolone, the only neuroprotective
      drug proven in patients with acute spinal cord injury may prevent the secondary
      injury after an initial trauma. Secondary vascular injury develops after
      experimental spinal cord trauma. In this study we examined the effects of U
      50488H on post-traumatic vascular injury based on the measurement of vascular
      permeability, edema and neutrophil infiltration in a rat spinal cord injury
      model. Vascular permeability was assessed by vascular extravasation of
      fluorescein isothiocyanate conjugated dextran (FITC-D), a macromolecular tracer.
      Tissue edema was determined by percentage water content and neutrophil
      infiltration by myeloperoxidase (MPO) activity, a marker enzyme for neutrophils.
      U-50488H at doses of 5, 10, 20 and 40 mg/kg i.p. administered twice (0.5 h before
      and 0.5 h after trauma) reduced vascular permeability in a dose-dependent manner.
      More frequent dosing (10 mg/kg, 0.5 h before and 0.5, 2, 8 and 22 h after injury)
      reduced vascular permeability 24 h after injury. U-50488H also reduced edema
      formation but did not affect neutrophil infiltration. Results from this study
      raise the possibility that the neuroprotective effect of U-50488H involves a
      secondary vascular event.

PMID- 8281453
TI  - Structure and plasticity of newly formed adult synapses: a morphometric study in
      the rat hippocampus.
AB  - Increasing evidence suggests that synaptic structure represents a plastic feature
      of the neuron, although the plastic nature of newly formed and existing adult
      synapses has not yet been fully characterized. Following ipsilateral entorhinal
      cortical lesions, the rat dentate gyrus offers an excellent model for studying
      synaptogenesis and plasticity in the adult central nervous system. Unilateral
      entorhinal lesions were performed in young adult male rats. Synaptic counts and
      structural features were quantified at 3, 6, 10, 15, and 30 days post-lesion. The
      lesions resulted in an 88% synaptic loss in the denervated dentate middle
      molecular layer, which was followed by a period of rapid synaptogenesis. Synaptic
      element size decreased during the period of maximal synaptogenesis, which was
      associated with a peak in the presence of non-vesicular and perforated synapses.
      Following this period, synapses showed a gradual increase in the size of their
      pre- and postsynaptic elements. These data support the suggestion that newly
      formed adult synapses have smaller synaptic components than existing adult
      synapses (resembling synapses seen during development), and increase in size over
      time with usage. The results are discussed in terms of synaptic structural
      development and plasticity in the adult central nervous system.

PMID- 8281454
TI  - Intracranial injection of Fluoro-Gold results in the degeneration of local but
      not retrogradely labeled neurons.
AB  - Small volumes of either Fluoro-Gold (hydroxy-stilbamidine) or physiological
      saline were pressure injected into the striatum of adult rats. This paradigm is
      essentially the same as that used by neuroscientists who inject small quantities
      of Fluoro-Gold into brain structures to reveal neuronal connections. Using a
      modified de Olmos' cupric-silver technique, virtually no degeneration could be
      detected as the result of saline injection at any time point examined. However,
      comparable injections of Fluoro-Gold resulted in conspicuous cell body and
      terminal degeneration within the striatum 1-10 days post injection. Terminal
      degeneration within the substantia nigra pars reticulata could also be seen 2-10
      days after injection. Examination of cells of the compacta region revealed
      conspicuous retrograde uptake of Fluoro-Gold, although none of these cells
      exhibited any evidence of neuronal degeneration at any postoperative time
      examined.

PMID- 8281455
TI  - Thyrotropin-releasing hormone (TRH) neurons sprout in cervical spinal cord of
      Wobbler mouse.
AB  - The present study was undertaken to quantify the immunocytochemical changes for
      thyrotropin-releasing hormone (TRH) within the ventral horn of the cervical
      spinal cord from Wobbler (wr/wr) mice selected at postnatal ages 3 weeks to 5
      months compared with the normal phenotype (NFR/wr) littermates as well as mice
      from two related normal mouse strains: the NFR/N parent strain, and the closely
      related C57B1/6N mouse strain. The immunoreactive (IR) neuronal processes
      containing TRH appeared in all specimens within Rexed's laminae VIII, IX, and X.
      Compared with the normal (C57B1/6N, NFR/N) specimens, the pair-matched normal
      phenotype (NFR/wr) and Wobbler (wr/wr) specimens possessed significantly greater
      numbers of IR-TRH containing processes at every age studied. Compared with the
      normal phenotype (NFR/wr) specimens, greater numbers of IR-TRH containing
      processes appeared in the ventral horn region studied from the Wobbler (wr/wr)
      specimens taken early (Stage 1) as well as later (Stages 3 and 4) in the
      motoneuron disease. An age-related decline in the number of IR-TRH processes was
      apparent among the specimens from the Wobbler mouse strain (NFR/wr, wr/wr), but
      not the normal (NFR/N, C57B1/6N) mouse strains. The data suggest that TRH may
      play a significant role in the Wobbler disease, possibly even before the symptoms
      become apparent. In addition strain-related differences exist which may be
      important to the etiology of the Wobbler disorder.

PMID- 8281456
TI  - Co-distribution of protease nexin-1 and protease nexin-2 in brains of non-human
      primates.
AB  - The protease nexins are protease inhibitors which regulate key blood coagulation
      proteases and which appear to be involved in certain physiological and
      pathological processes in the brain. Protease nexin-1 (PN-1), a potent inhibitor
      of thrombin, can regulate processes on cultured neurons and astrocytes. Protease
      nexin-2 (PN-2), a potent inhibitor of coagulation factor XIa, is identical to the
      secreted form of the Alzheimer's amyloid beta-protein precursor. In the present
      studies, PN-1 and PN-2 were analyzed in different tissues of monkey using
      monoclonal antibodies for either quantitative immunoblotting or specific
      [125I]protease-binding assays. PN-1 was detected only in brain. PN-2 was most
      abundant in brain, followed by testis and to a lesser extent kidney. Other
      tissues examined including spinal cord, heart, pancreas, spleen, liver, lung and
      muscle were essentially devoid of both PN-1 and PN-2. Within the brain, the
      levels of PN-1 and PN-2 were highest in the parietal cortex and lowest in the
      cerebellum and brainstem. The thalamus and striatum contained intermediate
      amounts of both proteins. Aged Cebus monkey cerebral cortical tissue contained
      slightly lower levels of PN-1 than did the middle-aged or young monkey tissue.
      The co-distribution of PN-1 and PN-2 in brain, their relative abundance in brain
      cortex, and previous studies on their functions suggest that in the brain they
      may participate in the regulation of blood coagulation and cell growth and
      differentiation.

PMID- 8281457
TI  - Ibotenic acid-induced lesions of the medial preoptic area/anterior hypothalamus
      enhance the display of progesterone-facilitated lordosis in male rats.
AB  - Electrical lesions of the medial preoptic area/anterior hypothalamus (MPOA/AH)
      have been reported to enhance the display of steroid-induced lordosis in
      castrated male rats. This study employed the cell body-specific neurotoxin,
      ibotenic acid, to ascertain whether neurons originating in this region (as
      opposed to axons of passage) tonically inhibit steroid-induced lordosis in adult
      male rats. Castrated, adult Long-Evans males received bilateral electrical
      lesions or injections of ibotenic acid or vehicle aimed at the MPOA/AH. Following
      administration of estradiol benzoate (EB) and progesterone, lordosis quotients
      (LQs) and lordosis ratings (LRs) were significantly higher in groups of rats with
      electrical lesions (LQ = 62.2 +/- 15.1; LR = 1.22 +/- 0.34) and ibotenic acid
      induced lesions (LQ = 58.1 +/- 12.2; LR = 0.99 +/- 0.24) than in the control
      group (LQ = 12.8 +/- 7.3; LR = 0.22 +/- 0.13). To determine whether this
      enhancement of receptive behavior in MPOA/AH-lesioned males was an effect on
      estradiol-induced, as compared to progesterone-facilitated lordosis, groups of
      castrated rats in a second experiment received bilateral injections of ibotenic
      acid or vehicle aimed at the MPOA/AH and were tested for lordosis after
      administration of EB alone and again after injection of progesterone. Following
      treatment with EB alone, rats with ibotenic acid-induced MPOA/AH lesions tended
      to be slightly less receptive than control animals. However, following injections
      of progesterone, LQs and LRs were higher in the MPOA/AH-lesioned group than in
      the control animals, as had been observed in the first experiment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8281458
TI  - Multiple cycles of dose-intensive cyclophosphamide, etoposide, and cisplatinum
      (DICEP) produce durable responses in refractory non-Hodgkin's lymphoma.
AB  - Patients whose lymphoma is resistant to standard treatment regimens continue to
      do poorly, with only an occasional patient achieving long-term remission even
      with bone marrow transplantation. Twenty-three patients with primarily refractory
      (11), or refractory relapsed (12) non-Hodgkin's lymphoma were treated with
      repeated cycles of dose-intensive cyclophosphamide, etoposide, and cisplatin
      (DICEP) without bone marrow transplantation. Each cycle of DICEP consisted of
      cyclophosphamide (2500 mg/m2/day, days 1-2), etoposide (500 mg/m2/day, days 1-3),
      and cisplatin (50 mg/m2/day, days 1-3). Twelve patients (52%) have achieved a
      complete response and 6 (26%)r a partial response. Three of the complete
      responders remain continuously free of disease for 19, 29, and 32 months, and 3
      more are disease-free at 58, 59, and 65 months after receiving further therapy.
      Three-year survival for all patients is 45%. Patients with a good initial
      performance status (Zubrod 0 or 1) had a 58% complete response rate and a 2-year
      survival rate of 53%. One of 19 patients with an initial performance status of 0
      or 1 had treatment-related mortality. Repeated cycles of DICEP can produce long
      term responses in patients with refractory non-Hodgkin's lymphoma.

PMID- 8281459
TI  - Re: "Treatment of advanced colorectal cancer with recombinant interferon alpha
      and fluorouracil: activity in liver metastasis".

PMID- 8281460
TI  - Re: "Oncology drug discovery and clinical trial testing: who's listening?".

PMID- 8281461
TI  - Double modulation of 5-fluorouracil in the treatment of advanced colorectal
      carcinoma: report of a trial with sequential methotrexate, intravenous (loading
      dose) folinic acid, 5-fluorouracil, and a literature review.
AB  - 5-Fluorouracil (5-FU) modulation with either folinic acid (FA) or methotrexate
      (MTX) has improved 5-FU's potential cytoreductivity. We combined MTX and FA with
      5-FU to further augment 5-FU's cytoreductivity. Patients (n = 34) with advanced
      colorectal carcinoma were first given intravenous MTX (escalated from 30 mg/m2 to
      70 mg/m2). FA (100 mg/m2) was infused 17-24 hr later, followed by 5-FU (600
      mg/m2). Oral rescue doses of FA were begun 24 hr after MTX. Patients were treated
      every 2 weeks. No previously treated patient (n = 6) responded. Eight of the
      remaining 28 (29%) (95% confidence interval, 15-47%) patients achieved a PR.
      Median survival was 9.3 months. Toxicity (primarily gastrointestinal)
      necessitated dosage modification in 10 patients (29%). These results, in addition
      to a literature review, reveal that the manipulation of 5-FU by two modulating
      agents does not improve the response rate seen with single-agent modulation.

PMID- 8281462
TI  - Biological study of R24 mouse monoclonal antibody in patients undergoing
      thoracotomy for pulmonary metastases from soft tissue sarcoma.
AB  - The disialoganglioside GD3 is expressed on the surface of soft tissue sarcoma,
      malignant melanoma, and other malignant cells and is, therefore, a potential
      target for therapeutic monoclonal antibodies. Intravenously administered R24, a
      murine IgG3 monoclonal antibody to GD3, induces inflammation and tumor regression
      at sites of metastatic malignant melanoma. R24 5 mg/m2 was given intravenously
      every other day for six doses to 10 patients with pulmonary metastases from a
      primary soft tissue sarcoma of the extremity for whom thoracotomy was planned.
      Resected tissue was available from 7 patients. All metastases expressed GD3;
      however, expression was heterogeneous within tumors, and in no tumor were more
      than 80% of the cells GD3 positive. A mild to moderate infiltrate consisting of
      mononuclear cells with T-cell markers was identified around or within pulmonary
      metastases in 6 patients. Tolerable acute allergic reactions occurred in all
      patients, but 3 patients had severe chest tightness and bronchospasm that limited
      the planned therapy. The setting of thoracotomy for metastatic disease provides
      an ideal system for studies on the pharmacology and biological effects of
      monoclonal antibodies that target soft tissue sarcoma antigens.

PMID- 8281463
TI  - Variable activity of protein tyrosine kinase in apparently normal thyroid glands.
AB  - We examined protein tyrosine kinase (PTK) activity in apparently normal thyroid
      tissue (n = 22) obtained from patients undergoing thyroid surgery for papillary
      thyroid cancer or benign disease. The PTK activity in apparently normal thyroid
      tissue from patients with papillary thyroid cancer progressively was elevated in
      the cytosolic fraction compared with that from patients without cancer (p <
      0.05). The cytosolic proportion of PTK activity was also significantly increased
      in the normal thyroid tissue of patients with cancer (62% vs. 51%, p < 0.05).
      These findings suggest that alterations in PTK activity may indicate apparently
      normal thyroid tissue at increased risk of developing malignancy.

PMID- 8281464
TI  - Reverse transformation and genome exposure in the C6 glial tumor cell line.
AB  - Reexpression of growth control and differentiation in response to physiological
      inducers can be demonstrated in some malignant cell lines, showing that they are
      not irreversibly transformed. This switch in phenotype is likely to reflect a
      changing pattern of gene expression, but it has not been known whether such
      cellular transitions involve major or only minor modulation of chromatin
      structure. We have studied growth control and accessibility of chromatin to DNase
      I in C6 glioma cells subjected to different growth regimens using an in situ nick
      translation assay to label the most exposed regions of nuclear chromatin. In
      fibroblasts and primary glia, exposed chromatin was localized mainly at the
      nuclear lamina. This readily labeled DNA structure was largely lacking in the
      malignant C6 glioma. When C6 cells were treated with dibutyryl cyclic AMP,
      exposed chromatin was reestablished around the nuclear periphery. This
      restoration of a normal genome exposure pattern required cytoskeletal integrity.
      Thus large-scale nuclear reorganization events proceed in parallel with
      phenotypic normalization. The changes in cell morphology, growth control,
      cytoskeletal organization, and chromatin exposure and localization are similar to
      the reverse transformation reaction in CHO-K1 cells, which is also regulated by
      the cyclic nucleotide system. Hydrocortisone and dexamethasone also restored
      genome exposure in C6 but less markedly than cAMP derivatives. Diverse
      transformed cells can thus respond to growth control stimuli with similar nuclear
      restructuring events, which presumably underlie changes in gene expression.
      Reverse transformation and redifferentiation appear to be alternative terms
      describing essentially the same biological phenomenon.

PMID- 8281465
TI  - The molecular genetics of Wilms tumor.

PMID- 8281466
TI  - Beware the wandering womb--painterly reflections of early gynecological theory.
AB  - Ailing women languishing in their sickrooms are common subjects in seventeenth
      century Dutch genre painting. Because the women in these paintings are usually
      young, pretty, affluent, and apparently in good health but for their listless
      poses and the concern shown by the physicians and maids who attend them, scholars
      have traditionally interpreted the scenes as moralizing sermons against
      illegitimate pregnancy or as satires against "quack" doctors. However, the
      medical context of the time suggest that these paintings actually reflect early
      gynecological theories, which assumed a uterine origin for all diseases of women.
      The details within the paintings point to the symptoms of, and attempted cures
      for hysteria, or furor uterinus, a female illness commonly diagnosed in the
      seventeenth century, but with a history as old as medicine itself.

PMID- 8281467
TI  - Positron emission tomography scanning in cancer.

PMID- 8281468
TI  - The role of chemotherapy in the treatment of primary tumors of the central
      nervous system.

PMID- 8281469
TI  - Has the cure of breast cancer with chemotherapy become a reality?

PMID- 8281470
TI  - Colorectal cancer: detection, treatment, and rehabilitation.
AB  - In the United States, colorectal cancer is the second most common cause of cancer
      mortality after lung cancer. However, incidence and mortality rates have been
      falling, reflecting improvements in primary prevention, early detection, and
      treatment. This article reviews the major advances in the understanding and
      management of colorectal cancer.

PMID- 8281471
TI  - New developments in monoclonal antibodies for cancer detection and therapy.
AB  - Monoclonal antibodies have provided clinicians with an intriguing, target
      specific approach to cancer management. Used alone or conjugated with drugs,
      toxins, or radionuclides, monoclonal antibodies have been shown to be useful in
      the detection and/or treatment of several cancers. Recent advances, such as the
      development of "humanized" antibodies, promise to increase their effectiveness
      even more. This article summarizes the status of the in vivo use of monoclonal
      antibodies for cancer detection and therapy.

PMID- 8281472
TI  - Evaluating cancer statistics.
AB  - Since 1967, the January/February issue of CA has contained a cancer statistics
      article with data prepared by the American Cancer Society's Department of
      Epidemiology and Statistics. Mr. Garfinkel, the former Vice President for
      Epidemiology and Statistics and Director of Cancer Prevention for the American
      Cancer Society, provides his insight to evaluate the trends that illustrate how
      much has already been accomplished in cancer control.

PMID- 8281473
TI  - Cancer statistics, 1994.

PMID- 8281474
TI  - Canadian heart health care--product and cost.

PMID- 8281475
TI  - Pseudoaneurysm after Bentall repair: magnetic resonance imaging assessment.
AB  - The prevalence and natural history of pseudoaneurysms (PA) following Bentall
      procedure has not been established. To determine the follow-up of PA in patients,
      the authors report their experience with magnetic resonance imaging (MRI) since
      1988. Spin-echo technique suspected PA in 19 of the 27 patients who underwent
      aortic valve and ascending aortic replacement between 1980 and 1991. Mean PA
      diameter was less than 4 cm in 13 patients (group 1) and at least 4 cm in six
      patients (group 2). Two patients in group 1 were lost at follow-up while two
      others in this group died after first spin-echo examination (one death was
      related to PA formation). Repeated MRIs were thus possible in nine patients in
      group 1 and in all patients in group 2, averaging 2.2 +/- 1.1 examinations per
      patient for group 1 and 1.8 +/- 1.1 for group 2. PA assessed in six group 1
      patients and one group 2 patient suggested thrombosed PA or postoperative
      hematoma. PA remained stable in two group 1 patients and one group 2 patient. One
      patient from group 1, in whom PA increased at follow-up, died suddenly. Four
      patients in group 2 required correction of PA, which had increased in diameter.
      Recently, addition of cine MRI has allowed visualization of turbulent flow within
      PA, thus increasing MRI specificity for PA diagnosis. In conclusion, MRI
      constitutes a reliable noninvasive imaging technique for diagnosis and follow-up
      of PA after Bentall repair.

PMID- 8281476
TI  - Pathophysiology of cardiac dysfunction in congestive heart failure.
AB  - Although various factors, such as myocardial infarction, pressure overload and
      volume overload, result in the development of congestive heart failure (CHF), the
      pathogenesis of contractile dysfunction in this situation is poorly understood.
      Loss of cardiac muscle due to myocardial infarction appears to activate several
      humoral and hormonal pathways, including the renin-angiotensin and sympathetic
      systems which serve as adaptive mechanisms to maintain cardiovascular performance
      at early stages of failure. However, under chronic conditions, an altered
      hormonal profile produces deleterious effects and permits transition from the
      compensated heart to the failing heart. Since several risk factors--such as
      hypertension, hypercholesteremia, stress, diabetes, smoking, ageing, obesity and
      lack of exercise--precipitate ischemic heart disease, it is possible that
      development of CHF due to myocardial infarction may vary according to the nature
      of these pathogenetic entities. While a great deal of research work remains in
      this area of investigation, it is becoming evident that cardiac dysfunction is
      intimately associated with calcium handling abnormalities of cardiac cells. In
      view of the role of sarcolemma, sarcoplasmic reticulum and mitochondria in
      regulating the intracellular concentration of Ca2+ and the importance of
      myofibrillar interaction with Ca2+, it appears that Ca2+ handling and Ca2+
      interaction abnormalities in the failing heart are due to remodelling of
      different subcellular organelles. Such a remodelling of the subcellular
      organelles may be due to changes in gene expression for different protein
      components or the interactions of proteins with phospholipids. Accordingly, it is
      proposed that new interventions, which could prevent the remodelling of
      subcellular organelles, be developed for improving the therapy of CHF.

PMID- 8281477
TI  - Jurassic heart: from the heart to the edge of chaos.

PMID- 8281478
TI  - Gliding window fast Fourier transform analysis--a new method for discovering the
      contribution of higher frequencies in signal-averaged ECG.
AB  - OBJECTIVE: An attempt to detect the 'parasitic contribution' of high frequencies
      in the electrocardiogram signal. DESIGN: A new method--gliding window fast
      Fourier transform analysis (GWFFTA)--was developed. It was applied in healthy
      subjects and in patients with acute myocardial infarction. SETTING: Faculty of
      Medicine and University Hospital. PATIENTS: The GWFFTA was used in 29 healthy
      volunteers and in a group of 30 patients with myocardial infarction, on day 7 to
      14 after admission to a coronary unit. INTERVENTION: Noninvasive examination,
      performed under standard conditions. MAIN RESULTS: GWFFTA provides better
      reproducible results compared with 'classic' fast Fourier transform analysis. The
      parasitic contribution of high frequencies within QRS complex and ST segment in
      patients with acute myocardial infarction is independent of presence or absence
      of late potentials. Contribution of high frequencies are three times higher in
      patients with acute myocardial infarction than in healthy probands. CONCLUSIONS:
      GWFFTA is a reproducible method of detection of high frequencies during whole
      heart activation. Contribution of high frequencies in patients with acute
      myocardial infarction reflects the state of the entire myocardium. It is also
      confirmed by the lack of correlation with the presence or absence of late
      potentials. Late potentials are more reflective of focal changes.

PMID- 8281479
TI  - Heparin monitoring during coronary intervention: activated clotting time versus
      activated partial thromboplastin time.
AB  - Activated clotting time (ACT) and activated partial thromboplastin time (APTT)
      are used for monitoring heparin therapy during coronary angioplasty. The purpose
      of this study was to determine which parameter is more useful clinically, and to
      assess the correlation between ACT and APTT. The authors measured these
      parameters at fixed intervals (0, 15, 30, 60, 150 and 240 mins) following
      intravenous heparin administration (12,500 +/- 3100 U) during coronary
      intervention in 39 patients. APTT rose to 'therapeutic' levels (true therapeutic
      levels have not been defined for these coagulation tests) more rapidly and fell
      to subtherapeutic levels more slowly than did ACT. The combination of a
      subtherapeutic ACT with a therapeutic APTT occurred far more often than did
      concordant therapeutic ACT and APTT values (69% versus 31%, P < 0.0004). There
      was a relatively poor correlation between ACT and APTT (r = 0.76). There were no
      abrupt closures in the study patients. It was concluded that subthreshold ACTs
      with high APTTs occur frequently, suggesting the improved suitability of ACT for
      intraprocedural monitoring of anticoagulation status. If one accepts the minimum
      amount of anticoagulation for prevention of thrombosis to be that which produces
      an ACT of greater than 300 s, then an APTT of greater than 90 s does not predict
      adequate anticoagulation.

PMID- 8281480
TI  - Deuterium oxide normalizes blood pressure and elevated cytosolic calcium in rats
      with ethanol-induced hypertension.
AB  - This study examined the effect of 10% deuterium oxide (D2O) in drinking water on
      systolic blood pressure, platelet cytosolic free calcium, aortic calcium uptake
      and renal vascular changes in rats with ethanol-induced hypertension. Eighteen
      male Wistar-Kyoto rats, age seven weeks, were divided into three groups of six
      animals each. Group I was given water and groups II and III, 5% ethanol in
      drinking water for the next seven weeks. After one week, systolic blood pressure
      in the ethanol-treated rats was significantly higher (P < 0.01) than in rats
      drinking water. After seven weeks, animals in group I were continued on water,
      group II on 5% ethanol, group III on 5% ethanol but with the addition of 10% D2O
      in their drinking water for the next seven weeks. After 14 weeks, systolic blood
      pressure, platelet cytosolic free calcium and aortic calcium uptake was
      significantly higher (P < 0.01) in group II rats (given ethanol for 14 weeks)
      compared with rats from other groups. Ethanol-treated rats also showed smooth
      muscle hyperplasia with some thickening of the wall and narrowing of the lumen in
      small arteries and arterioles of the kidney. D2O given to ethanol-treated rats
      normalized their blood pressure, platelet cytosolic free calcium, aortic calcium
      uptake and attenuated renal vascular changes.

PMID- 8281481
TI  - Acetylcholine stimulates release of endothelium-derived relaxing factor in
      coronary arteries of human organ donors.
AB  - OBJECTIVE: To determine whether cholinergic stimulation of human coronary
      endothelial cells induces the release of endothelium-derived relaxing factor
      (EDRF), denuded human coronary artery rings or denuded rabbit aorta rings were
      either directly perfused or superfused by the effluent of intact or denuded human
      coronary artery segments in a perfusion bioassay system. DESIGN: Coronary vessels
      were dissected from hearts of organ donors and prepared for use as donor segments
      and detector rings in the perfusion bioassay system. Segments were continuously
      perfused by an oxygenated Krebs-Ringer solution. Rings were suspended between two
      stirrups, one of which was connected to an isometric force transducer. They were
      either directly perfused (no tissue had been previously perfused by the same
      Krebs-Ringer) or superfused by the effluent of an endothelium-intact or -denuded
      coronary segment. Human rings were contracted with prostaglandin F2 alpha (2 x
      10(-6) M) and rabbit rings were contracted with phenylephrine (10(-6) M).
      RESULTS: Tension in detector tissue did not change during superfusion with
      effluent from endothelium-denuded or -intact human coronary artery segments,
      showing that there was no basal release of EDRF/nitric oxide (NO) in this
      preparation. Acetylcholine (ACh) (10(-6) or 10(-5) M) added to the perfusate
      increased the tension of the precontracted endothelium-denuded human rings
      directly perfused (50 +/- 32%) but not of the precontracted rabbit rings, showing
      that ACh is a potent agonist of human coronary vascular smooth muscle. ACh added
      to the coronary segment in the endothelium-intact superfusion mode had no effect
      in 33% or induced a small relaxation (8.8 +/- 1.6%) in 66% of the preparations.
      Hemoglobin (10(-5) M), a scavenger of EDRF/NO, caused a further increase in
      tension (32 +/- 15%). Adding calcium ionophore (A 23187;10(-5) M), which
      stimulates EDRF/NO release through a nonreceptor-mediated mechanism, to the
      coronary artery segment induced a relaxation in the endothelium-perfused detector
      rings which did not relax to ACh (30 +/- 2%); this relaxation was reversed by
      methylene blue (10(-5) M), a blocker of soluble guanylate cyclase. NO endothelin,
      a potent vasoconstrictor released by the endothelial cells, was detected in the
      effluent of intact coronary vessels. CONCLUSION: The results suggest that in two
      thirds of the six preparations studied, cholinergic stimulation can release EDRF
      from human donor coronary artery endothelial cells.

PMID- 8281482
TI  - Functional anatomy of the epicardial coronary veins.
AB  - OBJECTIVE: To describe the functional anatomy of the epicardial veins, including
      their dimensional changes in systole and diastole, and to relate these
      observations to the pattern of bloodflow in these veins. DESIGN: Using
      quantitative angiography and casts of epicardial veins in dogs, measurements of
      dimensions and anatomical patterns were observed. INTERVENTIONS: Venous
      angiograms were performed on 21 mongrel dogs. The diameters of epicardial veins
      in systole and diastole were measured using ECG gating. The dynamic anatomy of
      epicardial veins observed from video tapes was compared with static images and
      casts. RESULTS: The transverse diameter of the epicardial veins was similar in
      systole and diastole. The accuracy of measurement was limited by definition of
      the edges of the veins. An area of reduced contrast was observed in the posterior
      lateral section of the great cardiac vein and the appearance of gaps in the
      column of contrast material within the epicardial veins was consistently seen.
      CONCLUSIONS: These observations suggest that flow in epicardial coronary veins
      occurs as a bolus during each cardiac cycle.

PMID- 8281483
TI  - Diagnostic value of ECG patterns of right ventricular hypertrophy in children.
AB  - OBJECTIVE: To determine the diagnostic value of traditional criteria of right
      ventricular hypertrophy (RVH) in children. PATIENTS: The electrocardiograms
      (ECGs) of 1000 consecutive pediatric patients were reviewed. Children under three
      months old were excluded as were patients with QRS prolongation. RESULTS: Four
      hundred and thirty-four patients met all inclusion criteria. The medical records
      were then reviewed for diagnosis. Sixty-seven per cent had a diagnosis compatible
      with RVH. Of the ECG patterns evaluated, a precociously upright T wave in lead V1
      was most predictive with 99% specificity. Presence of a QR complex in lead V1 had
      a 96% specificity but R:S ratio, voltage criteria and rSR' incomplete right
      bundle branch block pattern had intermediate specificities of 66%, 66% and 52%,
      respectively. Sensitivities of 12.6%, 13.2%, 34.0%, 63.3% and 74.2% were
      calculated for upright T, QR complex, R:S ratio, voltage criteria and rSR',
      respectively. CONCLUSIONS: An upright T wave or qR pattern are highly specific
      but insensitive markers of RVH in children. In contrast, when an incomplete right
      bundle branch block exists, the rSR' pattern is a relatively sensitive but
      nonspecific predictor of RVH.

PMID- 8281484
TI  - Amiodarone-induced epididymitis: report of a new case and literature review of 12
      cases.
AB  - OBJECTIVE: To report a new case and review the literature of amiodarone-related
      epididymitis to improve knowledge of the clinical characteristics of this
      reaction. DESIGN: Cohort study. SETTING: Tertiary out-patient arrhythmia clinic.
      PATIENTS: Males currently treated for arrhythmias with amiodarone for at least
      two months. Thirty-two patients were identified and all were contacted. OUTCOME
      MEASURES: Swelling and or/pain in the scrotum with confirmation of noninfectious
      epididymitis by a urologist. DATA SOURCES: Bibliography (Medline and Embase) and
      databases (Manufacturer, Health Protection Branch, World Health Organisation).
      STUDY SELECTION: Four articles with case reports. Databases searched for these
      key words: amiodarone and epididymitis. RESULTS: A new case is reported. Twelve
      cases have been presented individually and six more described collectively. Times
      to onset range from four to 71 months, daily doses range from 200 to 800 mg. The
      reaction is self-limited, with or without amiodarone reduction, and does not
      require antimicrobial drugs, but a noninvasive urological examination may be
      warranted. CONCLUSION: Awareness by cardiologists will prevent unnecessary
      invasive urological investigations or antibiotic therapy.

PMID- 8281485
TI  - Transient hyperprolactinemia in gonadotropin-stimulated cycles for in vitro
      fertilization and its effect on conception.
AB  - The significance of transiently increased serum prolactin (PRL) levels on
      pregnancy rates in vitro fertilization (IVF) is unknown. The aim of this study
      was to evaluate PRL levels in IVF patients who conceived and in matched controls
      who did not. Ten IVF cycles resulting in pregnancy and forty nonpregnant cycles
      were compared. Prolactin was measured before ovarian stimulation with
      gonadotropins and estradiol (E2), progesterone (P) and PRL were measured 36
      hours, 12 hours, 10 minutes before and 12 hours after human chorionic
      gonadotropin (hCG) administration at mid-cycle. Serum PRL levels at various time
      were not significantly higher in the nonpregnant women than in the pregnant
      women. Twelve hours before hCG, P levels were significantly higher in the
      nonpregnant women than in the pregnant women (1.5 +/- 0.2 ng/ml [mean +/-
      standard error] and 0.9 +/- 0.3 ng/ml, respectively; P < 0.05). All women had
      transient hyperprolactinemia for one to three times during ovarian
      hyperstimulation. There was no correlation between PRL and E2 in either group.
      These results do not support the treatment of transient hyperprolactinemia with
      dopamine agonists in IVF patients.

PMID- 8281486
TI  - Primary IgA nephropathy: a nine-year clinicopathologic study in the Veterans
      General Hospital-Taichung.
AB  - IgA nephropathy (IgA N) is the most common type of primary glomerulonephritis
      (GN) diagnosed in Taiwan. From February 1983 to May 1992, 194 patients with
      primary IgA N, representing 25.3% of the primary GN, were diagnosed by renal
      biopsy at this hospital. Clinicopathologic correlation was made in 175 cases of
      IgA N with adequate clinical and pathologic data including light-(LM),
      immunofluorescent (IF) and/or electron-(EM) microscopy. Modified classification
      of Meadow et al. was adopted for the histologic grading of glomerular lesions.
      Forty-nine biopsies (28.0%) showed Grade IV and V lesions (Grade IV, 10.9%; Grade
      V, 17.1%, respectively) in association with a high level of serum creatinine and
      a lower frequency of gross hematuria when compared with lesions of histologic
      Grades I to III. Patients with Grade V lesions revealed a high frequency of
      hypertension as compared with those with Grades I to IV. The frequencies of
      nephrotic range proteinuria in those with various grades of IgA N was not
      statistically significant in this study. One hundred and thirty patients were
      followed up for one to eight and half years or until end-stage renal disease
      (ESRD) developed (mean 3.9 years), excluding the biopsies done at ESRD or from
      the graft kidney. Forty-two patients (32.3%) had chronic renal insufficiency, of
      those 25 (19.2%) eventually developed ESRD. Seventy-five percent of the patients
      with histologic Grades IV and V showed progressive renal disease, while only 16%
      of patients with Grades I to III lesions revealed progressive disease, the latter
      indicating a more benign course (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281487
TI  - Verification of endotracheal tube misplacement with the colorimetric carbon
      dioxide detector during anesthesia.
AB  - The sensitivity and reliability of the colorimetric end-tidal carbon dioxide
      detector (CETCO2) in verifying misplacement of endotracheal tube in the esophagus
      were assessed during induction of anesthesia using a conventional capnograph as
      control. Sixty patients of ASA physical status I and II undergoing elective minor
      surgery had their anesthesia induced with thiopental sodium (4-5 mg/kg, i.v.).
      Oral endotracheal intubation facilitated with succinylcholine (1.0 mg/kg, i.v.)
      was performed by junior residents. The time required for the appearance of
      discoloration from purple (< 2.5 torr) to tan-hued (3.8-7.6 torr) or yellow (>
      15.2 torr) on the CETCO2 (T1) was significantly shorter (3.83 +/- 0.92 second vs.
      8.23 +/- 1.14 second, p < 0.01) as compared with the initial display of the ETCO2
      waveform on the capnograph (T2). Out of 60 patients esophageal intubation
      occurred in 6 (10%). Two patients had the color of the CETCO2 changing from
      purple to tan-hued at the first breath but reverting to purple at the 2nd or 3rd
      breath. Thus, the sensitivity of CETCO2 was 97.0% (3.0% false positive) if the
      first breath was chosen as the point of determination. However, if it was set at
      the 6th breath or yellow was chosen as the color of determination, the
      sensitivity increased to 100% without either false positive or false negative. In
      conclusion, the CETCO2 detector is reliable for the detection of correct
      placement of endotracheal tube during induction of anesthesia, no matter whether
      Jackson-Rees modification Ayre's T-piece or anesthetic breathing circuit is used
      for ventilation.

PMID- 8281488
TI  - [The effect of surface area of active recording electrode to CMAP parameters].
AB  - The purpose of this study is to quantitatively evaluate the effect of surface
      area of active recording electrodes to CMAP. The APB muscles from 19 young
      healthy subjects were included. The evoked CMAPs from median nerve supramaximal
      stimulation at wrist were recorded with regular surface disc electrode. Then the
      active recording electrode were changed to 1/2 surface area of disc, 1/4 surface
      area of disc, monopolar needle and concentric needle at the same recording sites.
      Computer reading of the latency, duration, amplitude and surface area of the CMAP
      were done and compared to that of standard electrode. Results disclosed that
      decrease the surface area of active recording did not significantly influence the
      distal latency, duration, amplitude and surface area of the CMAP (p > 0.1),
      although tendency to increase the amplitude and area were noted. The recording
      abilities of the active recording and the surface area difference between active
      recording and reference were considered to be the contributing factors. In
      clinical application such as recording an area with skin defect, the surface area
      of active recordling electrode can be altered without significant distortion of
      CMAP parameters.

PMID- 8281489
TI  - [Hypothermia in the patients of emergency department].
AB  - In a 3-month period (January to March, 1992), patients with rectal temperature
      below 35 degrees C detected by an electrical rectal thermometer (Diatek, Inc, San
      Diego, CA) were enrolled. In addition to treatment of the underlying diseases,
      the patients were rewarmed with either a heating lamp (core temperature > 32
      degrees C) or warm fluid intravenous infusion and/or gastric lavage (core
      temperature < 32 degrees C). Patients' vital signs, serum potassium, pH, initial
      temperature, mean weather temperature, underlying disease and outcome were
      recorded and compared between survivors and non-survivors. We collected 23 cases
      with mean age of 71.6 years and mean core temperature, 33.32 degrees C (29.4-34.9
      degrees C). The diagnosis included hypoglycemia in 7 cases, sepsis in 3 cases,
      active TB in 2 cases, HHNK in 1 case, DKA in 1 case, UGI bleeding in 1 case,
      parkinsonism in 1 case, intracerebral hemorrhage in 1 case, urinary tract
      infection in 1 case, brain tumor post operation in 1 case, arrhythmia in 1 case,
      senile dementia in 1 case, COPD in 1 case and lung CA in 1 case. 12 (52%) cases
      died during admission. No significant difference in clinical parameters was noted
      between survivors and non-survivors. In conclusion, although in subtropic area,
      the hypothermic patients in our country cannot be overlooked. As patients are
      usually elder and have other diseases, the prognosis is correlated with the
      severity of the underlying disease. Alert, intensive care, prevention and
      treatment of the complications that arouse, and careful rewarming are necessary
      for management of such patients.

PMID- 8281490
TI  - [Clinical observation and analysis of febrile children].
AB  - Fever is an indication of acute disease, and needs special attention. To better
      understand the causes of fever in children, we analysed the records of 100
      febrile children who were admitted to this Hospital from June 1987 to December,
      1989. In these 100 cases, 7 days' fever prior to admission included 32 cases
      (32%); 7 to 14 days' fever prior to admission, 43 cases (43%); over 14 days' pre
      admission, 25 cases (25%). The age distribution was younger than 1 month, 3
      cases; 1 month to 1 year, 52 cases; 1 year to 2 1/2 years, 20 cases; 2 1/2 years
      to 5 years, 16 cases; 5 to 10 years 6 cases; older than 10 years included 3
      cases. Post-admission diagnoses of these children showed most had an infectious
      disease: 86 cases; "summer fever": 5 cases; perineal abscess: 1 case; cellulitis:
      1 case; leukemia, 2 cases; 5 were from other causes. Fevers were more prevalent
      in summer. In conclusion, the most common cause of prolonged fever in children is
      infectious disease 86%, with the highest incidence of age distribution under 2
      1/2 years old, with 73%. The case distribution showed a prevalence in summer 43%.
      Almost all prognoses were good.

PMID- 8281491
TI  - [Clinical efficacy of cefmetazole in intraabdominal infection].
AB  - A number of different organisms can be isolated from intraabdominal infection.
      The most common are aerobic Gram-negative bacilli. Anaerobes are not unusual.
      From June 1989 to January 1990, Cefmetazole was administered to 23 patients with
      intraabdominal infection at Veterans General Hospital-Taipei. There were six
      patients with spontaneous bacterial peritonitis, five biliary tract infection,
      five liver abscesses, five with pelvic inflammatory disease, one acute ruptured
      appendicitis and another intraabdominal abscess. In addition, ten patients had
      sepsis. Clinical response was satisfactory in 21 (91.3%) of 23 patients, and the
      microbiological eradication rate was 90% (36/40). One patient with Streptococcus
      and Bacteroides oralis liver abscess relapsed after organism eradication. Therapy
      failed in a case with Pseudomonas aeruginosa and Bacteroides fragilis infection.
      This study showed Cefmetazole to be an effective and safe antibiotic for
      treatment of intraabdominal infection.

PMID- 8281492
TI  - [Evaluation of conservative treatment for craniomandibular disorders].
AB  - The purpose of this study was to evaluate the effectiveness of conservative
      treatment for craniomandibular disorders. These included patient education and
      home care program, physical therapy, medication and flat occlusal splint therapy.
      Additionally the influence of sex, age, and duration of the use of the flat
      occlusal splint was evaluated. Forty-eight patients with craniomandibular
      disorders, collected from 1988-1991 in the Temporomandibular Joint Clinic of the
      Dental Department of Veterans General Hospital-Taipei, were studied. The results
      of this study indicated that (1) the treatment result of joint and muscle pain,
      joint sounds, limitation of mouth opening and jaw deviation after conservative
      treatment showed statistically significant improvement; and (2) this study was
      unable to demonstrate any influence of sex, age or duration of the splint use on
      the treatment effect. The results of this study indicate the need to further
      investigate the use of the occlusal splint for 24 hours, as compared with night
      times only.

PMID- 8281493
TI  - [Factors related to the choice of different hospitals providing Chinese
      traditional medicine].
AB  - A structured questionnaire was answered by patients who used the Outpatient
      Departments of two types of Chinese traditional medicine clinics: clinics
      associated with western-style teaching hospitals, and regular Chinese medicine
      clinics which were area-matched with, but not located in the teaching hospitals.
      The study applied the Andersen behavior model and discussed the factors related
      to the choice of one type or the other clinic by one-method-treatment (i.e.
      traditional only, not mixed with western, medicine) patients. The total number of
      valid questionnaires was 362. Under the analysis of logistic regression, the
      variables which were significantly related to the choice of the types of the
      hospitals were age, insurance status, first visit or follow-up, general health
      condition, severity of illness, musculoskeletal and neurological disorders. The
      older the patients, the more likely they were to visit teaching hospitals. First
      visit or uninsured patients also favored teaching hospitals. Patients with
      perceived stable conditions or more serious illness were likely to use teaching
      hospitals. Patients with musculoskeletal or neurological disorders favored
      regular clinics.

PMID- 8281494
TI  - Hyperglycemia induced by chemotherapeutic agents used in acute lymphoblastic
      leukemia: report of three cases.
AB  - Hyperglycemia may occur as a complication in patients with leukemia during
      induction therapy with L-asparaginase and steroids. The reported incidence is
      about 10%. The present report concerns three patients with acute lymphoblastic
      leukemia (ALL), complicated by hyperglycemia. Their ages were 10, 12, and 9
      years, respectively. Past histories were normal, with no diabetes mellitus or
      other endocrine disorders in their families. Case 1 was an obese boy who
      developed pancreatitis and diabetic ketoacidosis (DKA) in his remission induction
      therapy which had included both L-asparaginase and steroids. Cases 2 and 3 both
      presented with polyuria and elevated postprandial blood sugar. For all patients,
      insulin was administered to control their blood sugars; the maximal daily dosage
      of insulin dispensed was 2.1 U/kg, 0.5 U/kg, and 0.7 U/kg, respectively.
      Increased plasma insulin and C-peptide levels suggestive of insulin resistance
      were observed in Case 3. The outcome of hyperglycemia in these three patients was
      good. The symptoms of this complication may vary from mild glucose intolerance to
      severe, or even fatal, DKA. Thus, periodic determinations of urine glucose and
      postprandial blood sugar are important for early recognition to prevent further
      life-threatening consequences.

PMID- 8281495
TI  - Doppler velocimetry study of maternal hemodynamics and fetal vascular pattern in
      a case of chronic hypertension with superimposed severe preeclampsia and
      impending fetal death.
AB  - A case is presented of chronic hypertension with superimposed severe
      preeclampsia; absence of end-diastolic velocity in the umbilical artery had been
      noted at gestational age of 20 weeks. Because the fetus was previable, the mother
      was treated with pharmacotherapy according to the maternal hemodynamics;
      uteroplacental circulation and fetal vascular blood flow were monitored by
      Doppler velocimetry. Deterioration of the fetal condition occurred during
      crossover of maternal hemodynamics from a low-resistance to a high-resistance
      state. Serial Doppler velocimetry studies done within 40 minutes of fetal death
      are described. There were two types of absent end-diastolic velocity in the
      umbilical artery, and the pathophysiology and clinical management may be quite a
      different in these two situations.

PMID- 8281496
TI  - Malignant mixed mullerian tumor of the ovary: report of a case and review of the
      literature.
AB  - Malignant mixed Mullerian tumors (MMMTs) have been reported to occur in the
      female genital tract, especially in the uterine corpus. However, MMMT of the
      ovary is very rare and to best knowledge, no previous case has been reported in
      the literature of Taiwan. A 63-year-old female, with unique MMMT of the ovary, is
      described as having tumor with both carcinomatous and sarcomatous elements. The
      carcinomatous component was mainly composed of undifferentiated carcinoma. Small
      foci of glandular or papillary differentiation could be found. The sarcomatous
      component was composed of islands of atypical cartilaginous elements.
      Immunohistochemical studies revealed carcinomatous and heterologous sarcomatous
      elements respectively. Carcinomatous elements were cytokeratin and epithelial
      membrane antigen (EMA) positive, whereas heterologous sarcomatous elements were
      vimentin and S-100 positive. The patient received a left salpingo-oophorectomy
      and omentectomy without further chemotherapy or radiotherapy. The patient,
      already in the advanced stage, expired one month after the initial diagnosis.

PMID- 8281497
TI  - Intrathoracic extraskeletal Ewing's sarcoma: a case report and review of
      literature.
AB  - Extraskeletal Ewing's sarcoma (EES) is a rare tumor of soft tissue. As an
      uncommon clinical entity with histologic features similar to those of other small
      round-cell tumors, EES occasionally produces difficulty in diagnosis. Hence,
      diagnosis should be confirmed by histochemical, immunohistochemical and clinical
      findings. Here, we describe a man aged 29 years who had intrathoracic mass was
      diagnosed as EES after incisional biopsy of the tumor. The presence of glycogen
      in the tumor cells was demonstrated by periodic acid-Schiff (PAS) stain but
      immunoreactivity for cytokeratin, epithelial membrane antigen, leukocyte common
      antigen, desmin, actin and neuron-specific enolase were absent; vimentin was
      present. The patient was successfully treated with VIP regimen (etoposide,
      ifosfamide and cisplatin) followed by local irradiation. He remained alive
      without recurrence after one year. A review of the literature and recent advances
      in the treatment of EES are reported.

PMID- 8281498
TI  - [Giant cystic hygroma: a case report].
AB  - Cystic hygromas are congenital malformations of the lymphatic system appearing as
      single or multiloculated, fluid-filled cavities found mainly in the neck and
      axilla region. Antenatal ultrasound examination done in this case showed a
      suspicious giant cystic mass over the neck and chest area. At birth, the mass
      turned out to be a rare giant cystic hygroma measuring about 25cm x 26cm covering
      neck, anterior chest, axilla, proximal right upper limb, upper abdomen and upper
      back area. Because of some compromise to the infant's breathing, an emergency
      resection was done, and the infant tolerated the procedure well. Pathology report
      confirmed the diagnosis.

PMID- 8281499
TI  - Assessment of rehabilitation potential.
AB  - Physicians often have a powerful influence on patients and their families. If we
      enthusiastically recommend a realistic rehabilitation program, it will help our
      patients face the arduous process of functional recovery. Rehabilitation
      potential depends on many factors. Although there are scales that predict outcome
      following illnesses such as stroke or hip fracture, these outcomes are based on
      physical function. Until scales are developed that also look at psychologic and
      social and economic circumstance, the clinician's judgment is the only available
      method for determining rehabilitation potential. A screening tool that has been
      useful in assessing patients for admission to an acute rehabilitation inpatient
      unit is included in the Appendix. More research is needed to define which
      parameters in the physical, psychologic, and socioeconomic realms are useful in
      predicting rehabilitation potential. Funding for a prospective, long-term study
      is needed. Meanwhile, we must be vigilant in looking for the potential in all of
      our patients.

PMID- 8281500
TI  - Stroke rehabilitation.
AB  - It is clear from this article that additional studies examining what factors can
      be used to predict the outcome of stroke and what process achieves the best
      outcome most effectively need to be developed. The available data support the
      usefulness of a coordinated rehabilitation program in the treatment of the
      functional impairment that occurs after the stroke. The process of rehabilitation
      is a vibrant and exciting one for all individuals involved. It is a unique
      process in medicine in which the physician does not "do" anything to the patient,
      but rather he or she leads a multidisciplinary team in providing a milieu in
      which the patient can improve and better his or her functional abilities. The
      process of seeing patients improve and overcome the often overwhelming sequelae
      of stroke to return home in an independent fashion is gratifying not only for the
      patient but also for the members of the rehabilitation team. In rehabilitation
      there is a focus on not only the health of the patient but also a strong focus on
      the quality of life and functional independence once the patient returns home.

PMID- 8281501
TI  - Rehabilitation of fractures in the elderly.
AB  - Rehabilitation is the most important aspect of care after a fracture in an older
      person. Epidemiology, contributing factors, general principles of management are
      discussed in this article. Proper management requires knowledge of various
      mechanisms of injury, different forms of orthopedic treatments, interpretation of
      radiographs, and familiarity with available therapeutic modalities.

PMID- 8281502
TI  - Geriatric amputee rehabilitation.
AB  - Comprehensive rehabilitation of the amputee should be more than the provision of
      a prosthetic device. This is especially true for the geriatric amputee, whose
      needs are greater because of comorbidity, fragile social supports, and limited
      resources. This article reviews demographic information as well as preventive,
      preoperative, and immediate postoperative care of the amputee. Phantom sensation
      and pain and their management are addressed. Prosthetic components selection and
      the rehabilitation in different environments are considered, as is the care of
      the bilateral amputee and the patient with dual disability.

PMID- 8281503
TI  - Deconditioning.
AB  - Many authors have stressed the negative effects of prolonged immobility by
      emphasizing organ system changes. When treating individuals for various medical
      problems, equal regard should be given to functional decline as well. Beneficial
      exercise programs can be adapted for geriatric populations regardless of their
      disability. As the geriatric population increases, competition for health care
      resources increases as well. Emphasis should be placed on community-based
      programs that value prevention, restoration, and maintenance as worthwhile
      endeavors. Exercise should be the foundation for these programs and the goal
      should be to maximize functional skills. The benefits of exercise (Table 4) are
      physiologic, psychologic, and sociologic and greatly affect the perceived quality
      of life (Table 5). The adage "use it or lose it" should be heeded by all age
      levels. As we get older, it becomes more difficult to maintain physical
      conditioning, which can be discouraging to some and challenging to others.
      However, the importance of maintaining fitness with our advancing years is
      becoming increasingly clear. Bortz has stated that disuse syndromes affect far
      too many people in their later years. He challenges older people to live active
      lives to the end and ideally compress morbidity into a final short period of
      life.

PMID- 8281504
TI  - Movement disorders in geriatric rehabilitation.
AB  - This article discusses the role of rehabilitation in movement disorders in the
      elderly. Diagnosis and differential diagnosis are discussed with an emphasis on
      the akinetic rigid syndromes. Treatment and its complications are specifically
      addressed. The hyperkinetic movement disorders are considered separately. New and
      impending advances in therapy are examined.

PMID- 8281505
TI  - Rehabilitation of the elderly patient with arthritis.
AB  - The rehabilitation of an elderly patient with arthritis involves a cooperative
      effort on the part of patients and their caregivers, therapists, and physicians.
      If treatment is begun early in the course of the disease, the onset of functional
      decline and disability may be delayed or prevented. It may be useful for patients
      to contact the American Arthritis Foundation for further information and referral
      to support groups. Older people with arthritis must be included at a societal
      decision-making level in helping plan, design, and monitor community projects
      where handicap access questions arise. A major problem for people with disability
      is often the barriers they encounter in the environment and the attitudes of
      society. Treatment goals should be discussed and agreed on, and education and
      psychologic support should be provided for patients and their families. Each case
      must be individually assessed and a set of tailor-made rehabilitation
      interventions prescribed. Rest, exercise (active or passive), joint splinting,
      massage, heat (moist or dry heat), cold, pharmacotherapy, joint injection,
      surgery, and complementary treatment modalities such as homeopathy, acupuncture,
      education, and psychosocial support all have their role in the rehabilitation of
      the elderly patient with arthritis. For most patients, the course and prognosis
      are excellent. In general strength, ROM, and joint function can be preserved or
      improved to the point that participation in normal activities of daily living is
      possible.

PMID- 8281506
TI  - Assistive devices and home modifications in geriatric rehabilitation.
AB  - Many older adults have difficulty with functional activities and do not recognize
      that help is available to them. Many assistive devices and home modifications
      exist that promote greater independence and safety for older individuals in the
      areas of mobility, self-care, and home management. Many factors must be
      considered in selecting an assistive device for an individual in order to meet
      the unique needs of that person.

PMID- 8281507
TI  - Measuring rehabilitation outcomes.
AB  - The best way to measure the outcomes of rehabilitation in the older person depend
      on the health problem, the setting, and the way the data will be used. The
      process of selecting rehabilitation outcome measures can be based on purpose,
      clinical relevance, test characteristics, and practical considerations. There is
      no one best measure for all uses. A small set of measures that complement each
      other may be the most useful choice for the clinician wishing to measure the
      effect of treatment.

PMID- 8281508
TI  - Funding and policies affecting geriatric rehabilitation.
AB  - Policy makers and practitioners are increasingly acknowledging the need to shift
      health care expenditures toward cost-effective strategies that reduce disability
      and dependency in older persons. That need is driven by current research on
      disability and population aging, disability interventions, and the inadequacy of
      the existing service delivery system for chronic care needs. How disability and
      dependency should be reduced most effectively and efficiently is a critical yet
      unanswered policy question.

PMID- 8281509
TI  - Psychologic care of the older rehabilitation patient.
AB  - Rehabilitation of older persons must include adequately addressing psychologic
      issues. These issues range across detection and treatment of mental health
      problems, helping the team understand the patient's psychologic needs and
      characteristics and prepare for discharge back to the community. The older person
      is unique in many ways in rehabilitation and it is possible to overlook many
      important psychologic issues. Appropriate assessment is the beginning point of
      good treatment. However, proper treatment does not end with amelioration of
      mental health problems. Strengthening the older person's abilities to cope with
      life-long challenges also is important.

PMID- 8281510
TI  - Rehabilitation in the nursing home.
AB  - Despite the considerable challenges to providing high-quality rehabilitation in a
      long-term care facility, growing demographic and fiscal pressures are likely to
      push the nursing home into the forefront of rehabilitation for the frail elderly.
      Model programs have been implemented in recent years that present alternative
      ways to increase access to skilled services and improve quality of care in
      nursing homes without a drastic increase in costs. The teaching nursing home
      program has supported projects to make longterm care facilities centers for
      education, innovative clinical care, and research, thus bringing nursing homes
      into the mainstream of the medical establishment. A majority of US medical
      schools have recognized the need for training in long-term care and have formed
      affiliations with nursing homes. The Department of Veterans Affairs has a large
      national system of nursing homes, which has made a significant contribution to
      the training of health professionals in many fields. Demonstration projects such
      as the Social Health Maintenance Organization and On Lok have sought to decrease
      the fragmentation of health care services for the elderly and bring nursing homes
      into a continuum of care. The adoption of the OBRA regulations is building a base
      for comprehensive assessment and improved provision of care in nursing homes
      nationwide. Nursing home rehabilitation has the potential to decrease
      institutionalization in the short-term resident, whereas maintenance therapy can
      improve quality of life and decrease the cost of caring for patients who must be
      institutionalized. But to achieve this potential, significant barriers must be
      overcome. Negative attitudes about aging and nursing homes percolate through all
      levels of health care from lack of reimbursement at the federal and state levels
      to the professional priorities that continue to favor "high-tech" medicine and
      stigmatize nursing homes and those who work in them, to low expectations of
      caregivers and the residents themselves. For nursing homes to provide the level
      of rehabilitative care that is now expected of them, current funding mechanisms
      and negative attitudes must be changed, and nursing homes must be recognized as a
      legitimate part of mainstream health care.

PMID- 8281511
TI  - Rehabilitation in the outpatient setting.
AB  - A working familiarity with rehabilitation techniques is absent from most primary
      care settings. Primary care clinicians can benefit greatly from better knowledge
      of the principles of geriatric rehabilitation. Physiatrists and geriatricians can
      have a greater impact if future research also explores the practical barriers to
      providing rehabilitation services outside institutional settings. An active,
      collaborative search for new models of care is needed. If more elderly citizens
      are to benefit from effective rehabilitation services, established geriatric
      rehabilitation programs must learn how to select from the many patients referred
      for evaluation those who will most benefit from outpatient rehabilitation
      services. Impending national health care reform creates a window of opportunity
      to establish rational systems to deliver health services designed for our aging
      population.

PMID- 8281512
TI  - Educating primary care physicians in geriatric rehabilitation.
AB  - This article has reviewed the current status of primary care physician education
      in rehabilitation and the potential effects of current educational inadequacies
      on use of rehabilitation. The epidemiologic data regarding disease, development
      of disability, resource utilization, and its relevance to curriculum selection
      for rehabilitation were examined. Health care resources are limited, and given
      the increasingly important role the rehabilitation will play in health care, it
      is important that our educational efforts promote optimal use of those resources.
      A variety of teaching methods and their potential utility were discussed.
      Educating primary care physicians in the proper use of rehabilitation is of
      immediate importance for the large and growing older population. The use of
      available data on disease prevalence and impact to direct educational efforts
      will maximize the beneficial effects of our educational investments. The improved
      use of geriatric rehabilitation can make a significant impact on the health and
      quality of life for millions of older Americans.

PMID- 8281513
TI  - Research in rehabilitation.
AB  - The field of geriatric rehabilitation is fertile ground for a wide variety of
      research investigations. Because the functional approach is the foundation of
      good geriatric care, opportunities for collaborative projects between
      geriatricians and physiatrists, rehabilitation therapists, psychologists, social
      workers, and nurses are numerous. Rehabilitation research is particularly
      appropriate for the emerging field of outcomes research. Because of the crisis in
      health care costs in the United States, it is likely that there will be an
      increasingly strong demand on the part of both government and insurers that
      rehabilitation clearly demonstrate positive outcomes in care. It will be the job
      of those in geriatric rehabilitation to ensure that the outcomes that are
      measured are geared to detecting real benefits for our patients and not just cost
      savings.

PMID- 8281514
TI  - A new approach in the diagnosis and follow-up of bladder cancer. FISH analysis of
      urine, bladder washings, and tumors.
AB  - The aim of the present study was to ascertain whether fluorescence in situ
      hybridization (FISH) of urine could be a useful approach in bladder cancer.
      Herein, we present the cytogenetic and FISH findings in patients with and without
      bladder cancer. The samples examined with FISH consisted of urine, bladder
      washings, and tumor tissue, when available. The results obtained show that the
      FISH technique, particularly when used on urine, is a very useful tool in the
      diagnosis, early detection, and management of bladder cancer.

PMID- 8281515
TI  - Double minutes are frequently found in ovarian carcinomas.
AB  - Double minutes (dmins) are acentric chromosomal-like entities that are important
      in the etiology of cancer because they are known to harbor amplified oncogenes
      and drug resistance genes. Because dmins can be unequally partitioned at mitosis
      they have the ability to confer genetic diversification rapidly. Selective
      pressures operative in vitro may be quite different than those in vivo;
      therefore, tumor cells which harbor dmins could be selected against during short
      term in vitro propagation. We wanted to determine the incidence of dmins in human
      ovarian cancer cells obtained from fresh ovarian specimens with an absolute
      minimum of culture time (6-24 hours). In "direct" chromosomal preparations
      obtained from these clinical specimens we found dmins present in 88% of these
      samples. This remarkable finding that dmins are found so frequently in ovarian
      cancers underscores the importance of gene amplification in human tumor biology.
      Therefore, the presence of dmins in patient specimens indicates that these
      unstable genetic elements may play a significant role in the maintenance or
      progression of malignancy.

PMID- 8281516
TI  - Telomere reduction in giant cell tumor of bone and with aging.
AB  - Giant cell tumor of bone is a benign, primary skeletal neoplasm that has an
      unpredictable pattern of biologic aggressiveness, and cytogenetically
      demonstrates genetic instability by exhibiting telomeric associations. Molecular
      analysis of telomeres from giant cell tumor of bone demonstrated reduction of
      telomere length (average loss of 500 base pairs) in eight individuals when
      compared with their leukocyte DNA. Those tumors which exhibited telomeric
      associations were found to have a greater reduction in telomere length than
      tumors not exhibiting them. For comparison, eleven cytogenetically healthy
      control individuals (7 females and 4 males, age range 2 weeks to 70 years) were
      included in this study. They demonstrated loss of telomere size (average 40 base
      pairs per year) with advancing age and the greatest rate of telomere reduction
      was identified in the young. Thus, the functional consequences of telomere
      shortening in a neoplastic cell may prove fundamental to sustaining the
      transformed phenotype in giant cell tumor of bone.

PMID- 8281517
TI  - Cytogenetic analysis of a benzpyrene induced osteosarcoma in the rat (Rattus
      norvegicus).
AB  - A cytogenetic comparison of primary and transplant tumor cell-lines, both
      originating from a benzpyrene induced osteosarcoma, with normal rat cell-lines
      (Rattus norvegicus) is presented here. In all tumor cell-lines tested, the number
      of chromosomes was increased by one or two. Using Giemsa-banding, structural
      chromosomal changes, i.e. a Robertsonian translocation t(4;4)(q10;q10) and an
      interstitial deletion del(6)(q11q16) could be recorded. Furthermore, staining of
      nucleolus organizer regions (NORs) revealed a shift in NOR activity from
      chromosome number 11 to 12 and a decrease in NOR activity at chromosome number 3.

PMID- 8281518
TI  - A mesenchymal chondrosarcoma of a child with the reciprocal translocation
      (11;22)(q24;q12).
AB  - The reciprocal translocation (11;22)(q24;q12) was observed in a seven day culture
      from a mesenchymal chondrosarcoma of the bone, a tumor not characterized
      cytogenetically so far. We suggest that because of the presence of a similar
      cytogenetic abnormality, mesenchymal chondrosarcoma may belong to the wide group
      of "t(11;22)-small round cell tumors".

PMID- 8281519
TI  - C-anaphase in a case of acute nonlymphocytic leukemia.
AB  - C-anaphase was seen in approximately 50% of bone marrow cells from a patient with
      acute nonlymphocytic leukemia (ANLL). The abnormality acting as a marker for the
      disease, being present at diagnosis, disappearing during remission and returning
      at relapse.

PMID- 8281520
TI  - Recurrent t(12;19)(q13;q13.3) in intracranial and extracranial
      hemangiopericytoma.
AB  - We report on a recurrent intracranial hemangiopericytoma cytogenetically studied
      after short-term culture. The tumor had a uniform karyotype
      47,XX,add(7)(q21),t(12;19)(q13;q13.3),del(13)(q14q22), +21. Remarkably, one case
      with an identical reciprocal (12;19) translocation has been previously reported
      as the sole cytogenetic change in a recurrent retroperitoneal hemangiopericytoma.
      This nonrandom structural change may characterize a subentity of
      hemangiopericytoma and might be of diagnostic value.

PMID- 8281521
TI  - Identification of a yeast artificial chromosome that spans the human papillary
      renal cell carcinoma-associated t(X;1) breakpoint in Xp11.2.
AB  - Recently, a specific chromosome abnormality, t(X;1)(p11;q21), was described for a
      subgroup of human papillary renal cell carcinomas. The translocation breakpoint
      in Xp11 is located in the same region as that in t(X;18)(p11;q11)-positive
      synovial sarcoma. We used fluorescence in situ hybridization (FISH) and somatic
      cell hybridization techniques to demonstrate 1) that the Xp11 translocation
      breakpoint in papillary renal cell carcinoma differs from that observed in
      synovial sarcoma and has a more proximal location, and 2) that an ornithine
      aminotransferase (OAT)L2 containing yeast artificial chromosome (YAC) spans the
      X;1 translocation. This YAC provides an ideal starting point from which the
      breakpoint itself and the gene(s) involved can be isolated and characterized.

PMID- 8281522
TI  - Chromosome abnormalities in cementifying fibroma.
AB  - Cementifying fibroma is the most frequent benign fibro-osseous odontogenic tumor.
      We found chromosome abnormalities in a second case of this type of benign tumor.
      The chromosome changes in both cases are different. The chromosome bands involved
      in our case have not been described before in any benign fibroma so far reported.

PMID- 8281523
TI  - Translocation of CD3D gene in an acute myeloid leukemia (M5) with
      t(11;17)(q23;21).
AB  - Cytogenetic studies in patients with acute leukemia showed structural
      abnormalities on chromosome 11 at band q23 in five cases. Four of these had acute
      lymphoblastic leukemia (ALL) associated with t(4;11)(q21;q23) and one case had
      acute nonlymphoblastic leukemia (ANLL) (M5) associated with t(11;17)(q23;q21). We
      examined the CD3D and c-ets-1 genes in the t(11;17)(q23;q21) patient to ascertain
      any association between them and the chromosome change. In situ hybridization
      results showed that unlike in other studied cases with rearrangements of 11q23,
      the CD3D gene in the t(11;17)(q23;21) is transposed to the der(17) chromosome,
      providing evidence for a different breakpoint in the 11q23 region.

PMID- 8281524
TI  - New variant t(9;11;14)(p22;q23;q24) suggests a translocation of 9p to 11q as the
      critical genetic event.
AB  - We describe a patient with M5a (FAB classification) associated with a new type of
      variant translocation (9;11), namely t(9;11;14)(p22;q23;q24). The translocation
      of chromosome fragment from 9p to 11q is the common feature among the five
      variant translocations in the literature and our patient.

PMID- 8281525
TI  - An ovarian thecoma with a single numerical aberration: +12.

PMID- 8281526
TI  - Translocation (8;12) in a patient with agnogenic myeloid metaplasia.

PMID- 8281527
TI  - Chromosomal abnormalities in a pineocytoma.

PMID- 8281528
TI  - Effects of nitrendipine and lisinopril on blood pressure and sodium excretion in
      ciclosporin-associated hypertension after heart transplantation.
AB  - Hypertension associated with ciclosporin A may be mediated by sodium and volume
      retention. Therefore, the effects of an antihypertensive therapy (6 weeks) with
      nitrendipine (10-20 mg twice daily) or lisinopril (10-20 mg once daily) on office
      blood pressure, 24-hour ambulatory blood pressure, and left ventricular function
      were evaluated in a randomised, double-blind cross-over trial in patients after
      heart transplantation. Nitrendipine and lisinopril were equally effective in
      lowering office and ambulatory systolic and diastolic blood pressures. After an
      acute sodium load (210 mval/2 h i.v.), sodium excretion was significantly
      increased during therapy with lisinopril but only slightly during nitrendipine,
      indicating that angiotensin-converting enzyme inhibition may improve the sodium
      retaining state of heart transplant recipients associated with ciclosporin A.

PMID- 8281529
TI  - Accelerated glycolysis in early hypertensive left ventricular hypertrophy.
AB  - Changes in energy metabolism have been demonstrated in established left
      ventricular hypertrophy (LVH). It is not known if cardiac energy metabolism is
      shifted toward anaerobic pathways during the early stage of hypertensive LVH.
      Accordingly, glycogen, pyruvate, and lactate levels from left ventricular
      homogenate were measured in 8-week-old spontaneously hypertensive rats (SHR) and
      normotensive Wistar-Kyoto rats (WKY). Systolic arterial pressure and left
      ventricular weight were determined to establish hypertensive state and LVH,
      respectively. The glycogen and pyruvate levels in SHR versus WKY were lower by 19
      (p < 0.05) and 12% (NS), respectively. The lactate level in the SHR was 14%
      higher (p < 0.05) than in WKY. The lactate/pyruvate ratio in the SHR was higher
      than in the WKY, but did not reach statistical significance. These data suggest
      that the anaerobic metabolism is induced early in the development of
      hypertension, before the development of substantial LVH.

PMID- 8281530
TI  - Glucose and lipid metabolism in essential hypertension: effects of diuretics and
      ACE-inhibitors.
AB  - Various aspects of carbohydrate and lipid metabolism were studied in two groups
      of patients with mild hypertension before and after 6 months' treatment with
      either lisinopril (n = 10) or hydrochlorothiazide (n = 10). A significant
      reduction of arterial blood pressure was seen after both treatment regimens.
      Circulating plasma glucose, insulin, C-peptide and triglyceride concentrations
      were measured at hourly intervals from 8.00 a.m. to 5.00 p.m. in patients on an
      isocaloric diet (35 cal/kg/day). Plasma glucose concentrations remained
      unchanged, while insulin and C-peptide concentrations were higher in association
      with hydrochlorothiazide treatment. Conversely, lisinopril-treated patients had
      lower C-peptide concentrations after treatment. The changes in daylong plasma
      glucose and insulin-stimulated glucose uptake increased after hydrochlorothiazide
      treatment and decreased following lisinopril. Lastly, plasma cholesterol
      concentrations did not change after lisinopril therapy, whereas plasma high
      density cholesterol decreased as a result of hydrochlorothiazide treatment.

PMID- 8281531
TI  - Plasma atrial natriuretic factor in uncomplicated acute myocardial infarction.
AB  - Plasma atrial natriuretic factor (ANF) levels were measured in 29 patients who
      had normal atrial hemodynamics on days 4 and 8 after an uncomplicated acute
      myocardial infarction (AMI). All patients had increased ANF levels on day 4. On
      day 8 of the ANF levels had declined significantly to normal values in 14
      patients with enzymatically smaller AMI and higher ejection fractions (> or =
      40%), while they remained elevated in 16 patients with larger AMI and lower
      ejection fractions (< 40%). The study data are compatible with increased
      secretion of ANF by the more extensively damaged left ventricles in AMI.

PMID- 8281532
TI  - Onset of intolerance symptoms during exercise testing is a reproducible threshold
      for evaluation of cardiac function.
AB  - Twenty-one male patients with a history of myocardial infarction underwent
      bicycle cardiopulmonary exercise testing. The onset of leg pain or dyspnea, which
      reflects anaerobic metabolism, was termed anaerobic exercise symptom threshold
      (AEST). Our aims were (1) to evaluate the temporal relationship between AEST and
      the ventilatory anaerobic threshold (VAT) and (2) to determine whether heart
      rate, rate-pressure product, exercise time, and the ventilatory parameters at
      AEST are reproducible and correlate with the same parameters at VAT. AEST
      overlapped VAT in 4 patients and lagged behind VAT in 15. AEST never preceded
      VAT. The mean exercise time at VAT was 4.1 +/- 1.2 min and at AEST 5.6 +/- 1.6
      min (p < 0.0001); the mean heart rate was 97 +/- 10 and 107 +/- 12, respectively
      (p < 0.001). The mean values of the rate-pressure product and the oxygen
      consumption at AEST were significantly higher than at VAT. The correlation
      coefficient ranged from r = 0.74 to r = 0.93. Fifteen patients were examined
      twice within 1 month; the above parameters were reproducible at AEST, VAT, and
      peak exercise. In conclusion, AEST, which is easily recorded during bicycle
      exercise testing, is useful as a reference point for evaluation and follow-up of
      the cardiac aerobic function.

PMID- 8281533
TI  - Ventriculoarterial coupling during low-level exercise testing after myocardial
      infarction.
AB  - To evaluate the change of ventriculoarterial coupling during low-level exercise
      in patients after myocardial infarction, the ratio of systolic blood pressure to
      left ventricular end-systolic volume (P/V ratio) and the ratio of systolic blood
      pressure to stroke volume (effective arterial elastance) were investigated using
      radionuclide angiography in 73 consecutive patients with a negative predischarge
      exercise test. The patients were divided into three groups according to their
      resting left ventricular ejection fraction: group A (n = 12) > or = 60%; group B
      (n = 32) 41-59%; group C (n = 29) < or = 40%. The ejection fraction increased
      significantly during exercise in all three groups. There was no significant
      difference in the change of the P/V ratio during exercise between groups A and B,
      but it was significantly smaller in group C. The effective arterial elastance
      increased during exercise in group A, did not change in group B, and decreased in
      group C. Thus, the augmentation of myocardial contractility was an important
      factor related to the increase in ejection fraction during exercise in patients
      with normal or slightly reduced cardiac function, whereas the decrease in
      effective arterial elastance was important in patients with poor cardiac
      function.

PMID- 8281534
TI  - A multivariate analysis of the diagnostic values of clinical examination,
      exercise testing and exercise radionuclide angiography in coronary artery
      disease.
AB  - Data of clinical examination, exercise testing and exercise radionuclide
      angiography in 102 patients referred for assessment of chest pain was included in
      a logistic regression to optimize the diagnosis of coronary artery disease with
      coronary arteriography as the reference investigation. None of the patients had
      other cardiac problems or previous myocardial infarction. In the absence of
      symptoms, exercise testing was continued until at least 80% of the theoretical
      maximal heart rate was attained. Each patient was characterized by the value of
      the logistic function or probability of coronary artery disease. A threshold
      value corresponding to 80% sensitivity of ROC graphs was determined. The
      significant variables were: a clinical variable--the type of chest pain as
      assessed by the clinical history; two radionuclide angiographic variables--the
      ejection fraction at peak effort and the corrected variation of ejection fraction
      between rest and stress, that is not taking into account possible decreases at
      the last increment of exercise. Coronary patients can be identified with an 80%
      sensitivity and 77% specificity on these criteria. This specificity is greater
      than that obtained by clinical examination and exercise testing alone (65%).
      Exercise radionuclide angiography may therefore reduce the number of unnecessary
      coronary arteriographies.

PMID- 8281535
TI  - Bidirectional shunt through a residual atrial septal defect after percutaneous
      transvenous mitral commissurotomy.
AB  - A residual atrial septal defect with bidirectional shunt was detected by
      transesophageal echocardiography in a 28-year-old man 3 years after percutaneous
      transluminal mitral commissurotomy (PTMC) with the antegrade transseptal
      technique. He had had severe mitral stenosis, pulmonary hypertension, and
      tricuspid regurgitation before the procedure. The result of PTMC was suboptimal,
      the pulmonary hypertension regressed only partially, and the tricuspid
      regurgitation remained severe. These factors contributed to the bidirectional
      shunt. A bidirectional shunt is known to be associated with systemic desaturation
      and a higher risk of paradoxical embolization and brain abscess. When PTMC is
      considered in patients with pulmonary hypertension and tricuspid regurgitation, a
      retrograde left ventricular approach with or without transseptal puncture can
      avoid the atrial septotomy, decrease the incidence of significant shunt, and
      should be a rational alternative.

PMID- 8281536
TI  - Cardiac myxoma metastasized to the brain: potential role of endogenous
      interleukin-6.
AB  - Metastasis of a cardiac myxoma to the brain is extremely rare. We present the
      case of a 70-year-old man who had an atrial myxoma and two metastatic myxomas in
      the brain. The intracranial lesions were in fact diagnosed before the cardiac
      myxoma, since the patient developed hemiparesis before his cardiac symptoms
      occurred. Computerized tomography of the brain showed two high-density lesions,
      the larger of which was removed surgically. Follow-up computerized tomography
      revealed a progressive enlargement of the second lesion which was then resected.
      Histopathological examination showed all lesions to the benign myxomas.
      Interestingly, high concentrations of interleukin-6 were present in the patient's
      serum and cardiac myxoma. Interleukin-6 may possibly potentiate metastasis of
      cardiac myxoma.

PMID- 8281537
TI  - Doppler echocardiographic assessment of left ventricular diastolic function in
      patients with progressive systemic sclerosis.
AB  - To investigate the diastolic function of the left ventricle in patients with
      progressive systemic sclerosis (PSS), 13 patients with PSS (3 males and 10
      females; group PSS) were examined by Doppler echocardiography. As a control 8 age
      matched healthy volunteers (3 males and 5 females; group H) were also examined.
      Pulse-wave transmitral Doppler flow velocity curves were digitized and curves of
      the first derivatives were obtained. In group PSS, total left ventricular wall
      thickness and left atrial dimension were increased, the ratio between the left
      ventricular end-diastolic dimension and the left ventricular wall thickness was
      decreased, late peak diastolic filling was increased, isovolumic relaxation time
      was prolonged, compared with group H. The patients with left ventricular wall
      thickening out of proportion to left ventricular end-diastolic dimension had
      decreased early peak diastolic filling. We conclude that patients with PSS have
      deterioration of left ventricular diastolic function, and the diastolic function
      is severely disturbed in patients with left ventricular wall thickening out of
      proportion to left ventricular end-diastolic dimensions.

PMID- 8281538
TI  - The effect of sulfinpyrazone on treadmill exercise-induced angina pectoris.
AB  - Suspecting that platelet thromboemboli could play a role in the pathogenesis of
      myocardial ischemia, we have done a random-order, double-blind, crossover study
      of the effect of the platelet-active drug sulfinpyrazone on treadmill exercise
      induced angina pectoris in 30 men with coronary artery disease. The mean duration
      of exercise before onset of angina was 43 s longer after taking sulfinpyrazone
      than before and 11 s shorter after taking placebo than before. Analysis of
      variance for crossover design showed that the mean difference between the values
      obtained before and after sulfinpyrazone was significantly different (p < 0.01)
      from the mean difference between the values before and after placebo.
      Sulfinpyrazone had no effect on the mean heart rate-blood pressure product at
      onset of angina, change in ST segment during exercise, or preexercise platelet
      aggregate ratio and bleeding time. Exercise until angina occurred did not affect
      the platelet aggregate ratio.

PMID- 8281539
TI  - Cardiac involvement in rheumatoid arthritis: an echocardiographic study.
AB  - Thirty-nine consecutive patients with rheumatoid arthritis (RA) and 40 control
      subjects were studied by echocardiography in order to assess the incidence of
      cardiac involvement in this disease. The occurrence of anatomic lesions in our
      series was lower than that observed in other studies. No differences in mean
      values of left and right ventricular diastolic function indexes obtained by
      Doppler echocardiography were found between patients and controls. However, in
      26% of patients with RA, left ventricular abnormalities probably secondary to
      myocardial fibrosis were observed.

PMID- 8281540
TI  - Effects of local steroid elution on chronic pacing threshold and impedance of
      endocardial pacemaker leads.
AB  - To study the effects of steroid elution on chronic pacing threshold and
      impedance, a 4-mm2 surface area lead with steroid (030-368, Telectronics; n = 9)
      was compared to the same lead without steroid (030-359, Telectronics; n = 9) 3
      months after implantation. The pulse duration thresholds of the steroid lead were
      significantly lower at 0.8, 1.6, 2.5, and 5.0 V. Impedance measured by telemetry
      at 0.8, 1.6, 2.5, 5.0 and 8.0 V pulse amplitude, and 0.05, 0.25, 0.5 and 1.0 ms
      pulse duration was similar for the two leads. Mean impedance was about 650 omega
      and did not change from 0.8 to 8.0 V. The local steroid elution reduced the
      pacing threshold, but had no influence on the impedance. The stable impedance
      indicates that the impedance of this lead was not modified by pulse-dependent
      variables and, therefore, can also be correctly determined at pulse amplitudes
      below 5.0 V.

PMID- 8281541
TI  - Use of monophasic action potentials to evaluate postpacing T wave changes.
AB  - We examined the relationship between postpacing T wave changes and monophasic
      action potentials recorded from the ventricle in dogs. MAPs were recorded from
      the right and left ventricle before and after cessation of pacing. The duration
      of the MAP was calculated as the time in milliseconds from the upstroke to 90%
      repolarization (MAPD90). T waves in limb leads were flat or had a biphasic
      pattern, eventually becoming negative after pacing. The Q-T interval of the
      escape beat after pacing was prolonged compared with the control. After right
      ventricular pacing, the average duration of MAPD90 in the right ventricle, but
      not in the left ventricle, was prolonged. (right MAPD: control 275 +/- 10 ms;
      after pacing: 311 +/- 17 ms, p < 0.05; left MAPD: control: 266 +/- 23 ms, after
      pacing: 284 +/- 26 ms, NS). After left ventricular pacing, the average duration
      of MAPD90 in the left ventricle, but not in the right ventricle, was prolonged
      (right MAPD: control: 247 +/- 75 ms, after pacing: 287 +/- 39 ms, NS; left MAPD:
      control: 257 +/- 23 ms, after pacing: 303 +/- 25 ms, p < 0.05). Furthermore, the
      average duration of MAPD90 at the pacing site became progressively prolonged over
      time. These results suggest that myocardial cells retain the memory of abnormal
      repolarization associated with pacing.

PMID- 8281542
TI  - Infective endocarditis in the transesophageal echocardiographic era.
AB  - During a 45-month period, 50 consecutive patients with infective endocarditis
      were evaluated at the National Taiwan University Hospital with emphasis on the
      role of transesophageal echocardiography (TEE) in the management of these
      patients. Among them, rheumatic heart disease was still the most common
      underlying cardiac disorder (10/50, 20%), while mitral valve prolapse (8/50, 16%)
      and congenital heart disease (8/50, 16%) were also frequently encountered. More
      than one third (19/50, 38%) had no underlying heart disease. Four intravenous
      drug abusers, quite rare previously in Taiwan, were found during the study
      period. Native valves involved were mostly mitral valve (n = 18), aortic valve (n
      = 15), and both mitral and aortic valves (n = 3). Tricuspid valve and pulmonic
      valve were involved in 3 and 2 patients, respectively. Streptococcus viridans was
      the leading microorganism isolated (21/50, 42%). Staphylococci and enterococci
      were found in 9 (18%) and 5 (10%) patients, respectively. Twelve patients (24%)
      were culture-negative in this series. Embolic complications occurred in 13
      patients (26%), with a total of 17 episodes. No significant correlation was found
      between the occurrence of embolization and the vegetation size or the location of
      the vegetation, if patients with right-sided valvular vegetation and no
      identifiable vegetation were excluded. Surgery was needed by 25 patients (50%),
      and mortality occurred in 6 (12%). TEE was superior to transthoracic
      echocardiography in the detection of vegetations at the mitral or prosthetic
      valves. Concerning the associated complications with infective endocarditis, TEE
      was also superior in estimating the severity of mitral regurgitation, recognizing
      ruptured chordae tendineae and detecting subaortic complications such as valve
      ring abscess and mitral valve perforation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281543
TI  - Electrocardiographic findings of heart rate and conduction times in athletic
      students and sedentary control subjects.
AB  - We have investigated resting electrocardiograms in 1,299 athletic students and
      151 sedentary control subjects. Bradycardia was significantly more common in
      athletes. The athletic group was divided according to a heart rate < 50, 50-100,
      and above 100 beats/min. Atrioventricular conduction time, prevalence of ectopic
      beats and other rhythms, parameters of right and left ventricular hypertrophy, ST
      elevation, and T wave amplitude were increased in the sinus bradycardia group. A
      significant negative correlation was found between heart rate and PQ duration in
      athletes. In the sinus tachycardia group, the PQ duration was shorter and the ST
      depression more prominent than in the other groups. The subjects were also
      divided according to PQ > or = 0.22, 0.21-0.12, and < 0.12 s. Parameters of left
      ventricular hypertrophy were markedly increased in athletes with PQ > or = 0.22
      s, while the heart rate was only slightly decreased, suggesting an association
      between prolonged atrioventricular conduction time and left ventricular
      hypertrophy. Incomplete right bundle branch block was associated with a lower
      heart rate, increased duration of QRS and QTC, voltage of precordial Q waves,
      indices of right ventricular hypertrophy, and negative T waves. These findings
      are typical of right ventricular hypertrophy, indicating a close relation of
      incomplete right bundle branch block to right ventricular hypertrophy.

PMID- 8281544
TI  - Electrocardiographic findings according to level of fitness and sport activity.
AB  - We have investigated 52 ECG parameters in 1,299 athletes and 151 control
      subjects. Data on fitness were available in 840 athletes. They were split in
      three groups according to level of fitness and compared with each other and the
      control group with regard to the ECG findings. The most marked findings with
      increasing fitness were lower heart rate, increased prevalence of bradycardia,
      increased precordial ST segment elevation, and increased T wave amplitudes. Only
      slightly increased parameters of right and left ventricular hypertrophy were
      found. A highly significant correlation was found between fitness and heart rate,
      while no such correlation was found between fitness and the Sokolow index. The
      athletes were subdivided according to sports activity, and ECG parameters were
      compared in endurance athletes, ball players, strength athletes, gymnasts, and
      controls. Apart from a lower heart rate in endurance athletes and ball players as
      compared with strength athletes and gymnasts, few differences were found between
      the athletic groups. The heart rate is the most important parameter reflecting
      level of fitness and sports activity. The differences in ECG findings are
      relatively minor and do not distinguish type of sport activity.

PMID- 8281545
TI  - Acute myocardial infarction and left ventricular aneurysm in a patient with
      normal coronary arteries.
AB  - A 25-year-old young man was admitted with typical manifestations of acute
      myocardial infarction. Cardiac catheterization performed 2 weeks later showed a
      left ventricular aneurysm and normal coronary arteries. Because of the unusual
      clinical features, an endomyocardial biopsy was done and revealed
      histopathological changes of acute myocarditis. Acute myocarditis presenting as
      acute myocardial infarction with left ventricular aneurysm formation at the same
      time was never reported before. The long-term prognosis of the patient with left
      ventricular aneurysm caused by myocarditis still needs further observation.

PMID- 8281546
TI  - An unusual case of Q fever endocarditis.
AB  - We describe a patient with unusual features of Q fever endocarditis. The unusual
      features of this case were the presence of an abscess surrounding the involved
      aortic valve and the appearance of circulating anticoagulants in the patient's
      serum.

PMID- 8281547
TI  - Discovering our roots: Colorado nurses leaders.

PMID- 8281548
TI  - Reform is here to stay.

PMID- 8281549
TI  - Influencing public policy: a community effort.

PMID- 8281550
TI  - Mandatory continuing education important.

PMID- 8281551
TI  - The occupational nurse and ergonomics.

PMID- 8281552
TI  - Mandatory continuing education under review.

PMID- 8281553
TI  - The hospice model: an alternative to euthanasia.

PMID- 8281554
TI  - Recipe for nursing.

PMID- 8281555
TI  - Nursing practice: who's in charge, now and in the future?. Interview by Judith
      Burke.

PMID- 8281556
TI  - Clinical practice guidelines: a view to the future.

PMID- 8281557
TI  - Combined Raman and SEM study on CaF2 formed on/in enamel by APF treatments.
AB  - Raman spectra containing the distinct band at 322 cm-1 due to CaF2 or CaF2-like
      material formed in/on fluoridated bovine enamel were recorded using a micro-Raman
      spectrograph. Due to increasing levels of background fluorescence with increasing
      thickness of enamel, the Raman measurements were carried out on thin regions of
      wedged enamel sections. The distribution of the CaF2 or CaF2-like material was
      estimated using a simple model. The results indicate that 1/3 of the total CaF2
      was concentrated within the narrow depth < 2 microns with high CaF2
      concentrations (> 10 wt%), and that the majority of the CaF2 was distributed over
      the depths up to 26 microns (1 wt% CaF2). SEM observations on fractured
      fluoridated enamel confirmed that morphological changes were present in the depth
      range comparable to that of the high CaF2 concentration region expected from the
      Raman analysis. In deeper regions where lower concentration (< 10%) but a large
      amount of CaF2 was still expected, the SEM images failed to distinguish between
      the normal and fluoridated enamel. After KOH treatment, the Raman spectra did not
      show evidence of the CaF2 peak and the SEM micrographs also confirmed the removal
      of globules. The peak position of the Raman band of the CaF2 formed by the
      fluoridation was identical to that of pure CaF2. However, the linewidth was 23 cm
      1 (FWHM) and a factor of 2 broader than that of pure CaF2 (12 cm-1). This implies
      that the lattice dynamics of the CaF2 formed by fluoridation is different from of
      pure CaF2, and that the material formed is 'CaF2-like' or 'disordered CaF2'.

PMID- 8281558
TI  - In situ remineralization of enamel lesions using continuous versus intermittent
      fluoride application.
AB  - Remineralization of early enamel lesions was studied in situ using a F chewing
      gum or a F-releasing device (FRD). Enamel specimens with subsurface lesions were
      mounted in removable lower appliances in 6 adults. A F-free dentifrice was used
      for all regimens. Test groups chewed five sticks/day (0.1 mg F/stick), or one FRD
      (0.5 mg F/day) was mounted in the midline of the appliance. The microhardness was
      measured after the 21-day intraoral exposure, and in vitro acid resistance
      testing was performed. Separate specimens were used to measure F content or
      changes in mineral density. Comparable values for both F gum and FRDs were higher
      (p > 0.05) than controls for acid resistance testing and percent
      remineralization. The F content for FRDs exceeded that of both F gum and
      controls.

PMID- 8281559
TI  - Effect of milk on cariogenesis.
AB  - Sprague-Dawley rats fed diet 2000, infected by Streptococcus sobrinus, and
      offered milk or lactose-reduced milk as drinking fluids developed essentially
      similar caries scores as controls given distilled water. In contrast, animals
      given fructose or sucrose solutions developed enhanced levels of caries.
      Significant differences were not detected in the S. sobrinus populations among
      the groups. In further experiments, the addition of sucrose to milk enhanced the
      severity of caries scores. However, sucrose-milk solutions were significantly
      less cariogenic than sucrose-water solutions. Animals fed sucrose (2-5%) milk
      solutions harbored enhanced populations of S. sobrinus. The results, overall,
      suggest that milk may have modest cariostatic properties when ingested at the
      same time as a cariogenic challenge.

PMID- 8281560
TI  - Effect of sucrose concentration on the cariogenic potential of pooled plaque
      fluid from caries-free and caries-positive individuals.
AB  - Pooled plaque samples were obtained from (1) coronal surfaces of two groups of
      caries-free (CF) subjects, (2) coronal 'white-spot' surface areas of a group of
      caries-positive (CP) subjects, and (3) exposed, sound root surfaces of root
      caries-free (RCF) and root caries-positive (RCP) subjects. The plaque samples
      were obtained before and 3 min after a 1 min rinse with a 0.5, 1, 2, 5 and 10%
      sucrose solution. Plaque fluid was then isolated from each plaque sample by
      centrifugation and analyzed for inorganic ions, organic acids, and pH values.
      With increasing sucrose concentration: (1) plaque fluid pH and the degree of
      saturation (DS) with respect to tooth mineral decreased; (2) the pH and DS values
      of CP and RCP samples were consistently lower than those of CF and RCF samples,
      respectively; (3) plaque fluid lactic acid concentrations increased and were
      consistently higher in the CP and RCP samples than in the CF and RCF samples,
      respectively, and (4) plaque fluid lactic acid concentrations leveled off between
      1 and 5% sucrose; this occurred at lower sucrose concentrations with CP and RCP
      samples than with CF and RCF samples, respectively. RCP samples contained
      consistently higher levels of mutants streptococci than RCF samples. The chemical
      composition of plaque fluids, following sucrose exposure, were found to correlate
      well with caries history. The observed differences in lactic acid concentrations
      in samples from CF and CP subjects are discussed with regard to differences in
      microbiological composition and possible differences in plaque permeability to
      sucrose.

PMID- 8281561
TI  - Factors related to fluoride retention after toothbrushing and possible connection
      to caries activity.
AB  - The aim of the present investigation was to study the brushing and toothpaste
      technique employed by caries-active and caries-inactive patients in a
      toothbrushing population. The study consisted of 47 patients at a public dental
      clinic in the County of Bohuslan, Sweden; 23 with low (group L) and 24 with high
      caries activity (group H). They were asked to brush their teeth with a fluoride
      dentifrice at the clinic using an identical technique to that which they employed
      at home. Various factors, such as brushing time, amount of dentifrice, water
      consumption and mouthrinsing habits after brushing, were carefully registered.
      Saliva samples for fluoride analyses were collected up to 45 min after brushing.
      The members of group L used less rinsing water (0.7 +/- 0.6 dl; mean +/- SD) than
      those of group H (1.9 +/- 1.0 dl, p < 0.001). Comparing the mouthrinsings with
      water after the brushing, a significantly higher frequency was observed in group
      H (3.6 +/- 1.9 rinsings) than in group L (1.5 +/- 0.7 rinsings; p < 0.001). There
      were no differences between the two groups regarding the amount of dentifrice
      used and the total brushing time. When the salivary fluoride concentration was
      plotted vs. time and the area under the curve (AUC) calculated, a significantly
      higher mean value was found in group L than in group H (p < 0.01). Calculation of
      the correlation coefficient (r) between the AUC value and the amount of water
      used gave r = 0.53 (p < 0.001) and between the AUC and the frequency of
      mouthrinsing r = 0.46 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281562
TI  - Urinary fluoride excretion in 4-year-old children in Sri Lanka and England.
AB  - Urine was collected over 24 h from children aged 4 years in Sri Lanka and
      England. Fifty-three children were from Dambulla, Sri Lanka, and 44 from
      Newcastle, England, both localities receiving drinking water containing 0.8-1.1
      mgF/l. Urine volume was measured immediately after the 24-hour collection and
      samples of the collection from each child were frozen for transportation prior to
      'blind' analysis in one laboratory for fluoride content. The mean 24-hour urine
      volumes were 504 ml (SD 198) in Sri Lanka and 449 ml (SD 196) in England (p =
      0.17). The mean F concentrations were 1.19 ppm (SD 0.63) in Sri Lanka and 1.02
      ppm (SD 0.42) in England (p = 0.12). The mean weights of fluoride excreted were
      0.55 mgF/day (SD 0.30) in Sri Lanka and 0.42 mgF/day (SD 0.19) in England (p =
      0.009). The distributions of weight of fluoride excreted were also dissimilar in
      shape between the two countries. The extent to which these small differences in
      fluoride excretion in urine reflect differences in fluoride intake needs to be
      investigated.

PMID- 8281563
TI  - Caries-preventive effect of two different topical fluoride concentrations with
      two different frequencies of application in preschool children.
AB  - The effects of standard topical amine fluoride solution (1% F) and a low-fluoride
      solution (0.5% F) with two different frequencies of application (5 and 10 times a
      year) on 2 years dental caries increment were compared in a double-blind clinical
      trial involving 199 kindergarten children. The results suggest that increased
      frequency of application of a low fluoride topical solution (10 times a year) may
      provide caries protection in preschool children with relatively high caries
      activity.

PMID- 8281564
TI  - Dietary habits and dental caries in a population of Spanish schoolchildren with
      low levels of caries experience.
AB  - The aim of this study was to analyze the relationship between current dietary
      habits and dental caries in schoolchildren from an area of Spain on which the
      prevalence of caries was low. The results of an epidemiological study conducted
      on a random sample of 893 children from the cities of Girona and Figueres are
      presented. The method of dietary interview consisted of a food-frequency
      questionnaire. This showed a positive relationship between dental caries and
      consumption of ice cream, pastries, cakes, sliced bread, on the one hand, and
      sugar-free chewing gum and sugar-free candies, on the other. A protective effect
      of skimmed milk and artificial sweeteners was also observed. Results reflect the
      role of certain foods in caries development, but also the outcome of selective
      dietary counseling to high-risk children.

PMID- 8281565
TI  - Long-term effect of xylitol chewing gum in the prevention of dental caries: a
      follow-up 5 years after termination of a prevention program.
AB  - About 65% of the original 258 children who participated in 1982-1984 in a caries
      prevention program involving the use of xylitol chewing gum were retrieved in
      1989 for a follow-up study. Ninety-five subjects from the original xylitol (X)
      group and 70 subjects from the original control (no-gum, C) group were available.
      In 1984, when the children completed the program at the age of 13-14 years, the
      caries scores were significantly lower in children who had used xylitol gums
      daily, compared with the C group. In 1989, 5 years after the discontinuation of
      the gum program, the difference between the X and C groups had continued to
      increase in favor of the X group. These effects were explained by assuming that
      the X gum program had facilitated the establishment of a low-virulent bacterial
      flora on the surfaces of the teeth, and especially on those teeth that erupted
      during the trial proper. This type of results are possibly helpful when
      evaluating cost-benefit ratios of caries prevention.

PMID- 8281566
TI  - Screening with conventional and digital bite-wing radiography compared to
      clinical examination alone for caries detection in low-risk children.
AB  - The study compared conventional and digital bite-wing screening, performed in
      combination with a clinical examination for caries detection, in 168 14-year-old
      children with little caries experience. Radiography revealed 2-3 times more
      carious lesions than did clinical examination. Conventional and digital
      radiography detected dentinal caries in only 1.6 and 1.1%, respectively, of the
      clinically sound surfaces. Conventional, as well as digital radiography revealed
      caries in 7% of occlusal surfaces suspected of caries after a clinical
      examination. Of the suspected approximal surfaces, conventional radiography found
      caries in 25%, and digital radiography in 19%. From these results, it may be
      appropriate to perform radiographic screening in combination with clinical
      examination when the purpose is to assess caries prevalence, and as a basis for
      individual treatment decisions, if treatment is offered to surfaces with enamel
      lesions. However, if treatment is offered only to surfaces with clinically
      detected lesions and to surfaces with radiographically perceived dentinal
      lesions, it may not be appropriate to perform radiographic bite-wing screening,
      as less than 2% of the treatment-demanding surfaces will be overlooked by
      clinical examination alone. Instead, selective radiography should be conducted of
      surfaces suspected clinically as being carious.

PMID- 8281567
TI  - Caries prevalence in 2.5-year-old children.
AB  - The prevalence of caries and gingivitis was determined clinically in 2.5-year-old
      children (n = 832) living in the southern suburbs of Stockholm. The occurrence of
      mutants streptococci and lactobacilli was determined in samples taken from the
      tongue and the buffer capacity of the saliva was measured. The parents answered a
      structured questionnaire concerning their children's dietary habits, oral
      hygiene, fluoride exposure and their social and ethnic background. Initial or
      manifest caries was diagnosed in 11.7 and 6.4% of the subjects, respectively.
      Seventy-two percent of the total number of caries lesions were localized to the
      maxillary incisors. Caries prevalence in children with an immigrant background
      was significantly higher (p < 0.001) than in children without. In the
      multivariate analysis, the variables significantly associated with caries were:
      colonization with mutans streptococci (p < 0.001), lactobacilli (p < 0.01) and
      children with immigrant background (p < 0.01). The study demonstrates an
      association between early colonization of cariogenic microflora and an increased
      risk of developing dental caries in very young children.

PMID- 8281568
TI  - Molecular conformation of patellamide A, a cytotoxic cyclic peptide from the
      ascidian Lissoclinum patella, by X-ray crystal analysis.
AB  - As part of a series of investigations into the conformational stability of a C2
      symmetric or related cyclic peptide isolated from the ascidian Lissoclinum
      patella, the molecular conformation of patellamide A, the chemical structure of
      which deviates slightly for C2-symmetry, was determined by X-ray crystal
      analysis. Patellamide A took on a saddle-shaped rectangular form and wrapped
      around the water and methanol solvents. This conformation which is very similar
      to that of C2-symmetric ascidiacyclamide would be proposed as a possible
      candidate for biologically "active" conformation.

PMID- 8281569
TI  - Synthesis of manool-related labdane diterpenes as platelet aggregation
      inhibitors.
AB  - Enantioselective total synthesis of the labdane diterpene (-)-1, was achieved
      starting from the R-(-)-enantiomer of the Wieland-Miescher ketone. The enantiomer
      (+)-1 was obtained by partial synthesis via microbial transformation of sclareol.
      These results established that the natural compound (+)-1, a platelet aggregation
      inhibitor, has a normal absolute stereochemistry like that of manool. The B
      norlabdane-related compound 44 was also synthesized using a novel ring
      contraction reaction.

PMID- 8281570
TI  - Antisweet natural products. VIII. Structures of hodulosides VI--X from Hovenia
      dulcis Thunb. var. tomentella Makino.
AB  - From the Fresh leaves of Hovenia dulcis Thunb. var. tomentella Makino, five five
      new dammarane glycosides named hodulosides VI-X (1-5) were isolated. Their
      structures were determined on the basis of chemical and spectral evidence.
      Hodulosides VII-X showed antisweet activities.

PMID- 8281571
TI  - Russuphelins B, C, D, E and F, new cytotoxic substances from the mushroom Russula
      subnigricans Hongo.
AB  - Five new chlorinated phenyl ethers, russuphelins B (2), C (3), D (4), E (5) and F
      (6) have been isolated from the mushroom Russula subnigricans Hongo, and their
      structures were elucidated by spectroscopic and chemical means. Russuphelins B
      (2), C (3) and D (4) exhibited cytotoxic activity in vitro against P388 leukemia
      cells.

PMID- 8281572
TI  - Studies on the constituents of Turkish plants. I. Flavonol triglycosides from the
      fruit of Rhamnus thymifolius.
AB  - Two new flavonol glycosides have been isolated from the fruit of Turkish Rhamnus
      thymifolius (Rhamnaceae) and their structures were elucidated as kaempferol-3-O
      alpha-L-rhamnopyranosyl(1-->3)-(4-O-acetyl)-O-alpha-L- rhamnopyranosyl-(1-->6)-O
      beta-D-galactopyranoside and kaempferol-4'-O-alpha-L-rhamnopyranosyl(1-->3)-O
      alpha-L-rhamnopyranosyl (1-->6)-O-beta-D-galactopyranoside based on spectral and
      chemical evidence.

PMID- 8281573
TI  - Antiulcer agents. III. Synthesis and antiulcer activity of N-[3-(3
      piperidinomethylphenoxy)propyl]pentacyclo[4.2.0.0(2,5).0(3,8).0 (4,7)]-octane
      carboxamides and related compounds.
AB  - The synthesis and antiulcer activity of highly strained cage compounds such as
      pentacyclo[4.2.0.0(2,5).0(3,8).0(4,7)]-octane (cubane),
      pentacyclo[4.3.0.0(2,5).0(3,8).0(4,7)]nonane (homocubane) and
      pentacyclo[5.3.0.0(2,4).0(3,6).0(5,8)]decane are described. Of the compounds
      obtained, N-[3-(3-piperidinomethylphenoxy)propyl]-4-piperidinocarbonylpen tacyclo
      [4.2.0.0(2,5).0(3,8).0(4,7)]octane carboxamide (26a) and N-[3'-(3'
      piperidinomethylphenoxy)propyl]-1-bromo-9, 9
      ethylenedioxypentacyclo[4.3.0.0(2,5).0(3,8).0(4,7)[nonane]-4- carboxamid e (26q)
      showed more potent antiulcer activity with very good cytoprotective ability in
      the HCl.ethanol-treated rat model. Compounds 26a and 26q exhibited H2-receptor
      antagonist potency (in vitro) comparable to that of ranitidine, but did not
      inhibit histamine-stimulated acid secretion (in vivo) in the gastric fistula rat
      model, when orally administered in the dose range at which antiulcer and
      cytoprotective activities were seen. The structure-activity relationships are
      discussed.

PMID- 8281574
TI  - Scrophulasaponins II-IV, new saikosaponin homologs from Scrophularia kakudensis
      FRANCH.
AB  - From the whole plants of Scrophularia kakudensis, three new saikosaponin
      homologs, named scrophulasaponins II-IV, were isolated, together with six known
      and four artifact saponins; their structures were elucidated by spectroscopic
      data and chemical evidence.

PMID- 8281575
TI  - Agapanthussaponins A-D, new potent cAMP phosphodiesterase inhibitors from the
      underground parts of Agapanthus inapertus.
AB  - The saponin fraction prepared from the methanolic extract of the underground
      parts of Agapanthus inapertus was found to exhibit inhibitory activity on cAMP
      phosphodiesterase (55.2%) at a concentration of 100 micrograms/ml. From this
      fraction, four new steroidal saponins, designated as agapanthussaponin A (1), B
      (2), C (3) and D (4), were isolated as the active principles, along with an
      inactive new furostanol saponin (5). The structures of 1-5 were determined by
      spectroscopic data and hydrolysis. The IC50 of 1-4 on cAMP phosphodiesterase were
      0.7, 1.2, 1.1 and 2.0 (x 10(-5) M), respectively, which are more potent than that
      of papaverine (IC50 3.0 x 10(-5) M).

PMID- 8281576
TI  - 2'-Hydroxymatteucinol, a new C-methyl flavanone derivative from Matteccia
      orientalis; potent hypoglycemic activity in streptozotocin (STZ)-induced diabetic
      rat.
AB  - The CHCl3 extract of Matteccia orientalis showed very strong hypoglycemic
      activity in streptozotocin (STZ)-induced diabetic rats. A new C-methyl flavanone
      derivative, 2'-hydroxymatteucinol (3) was isolated from the hypoglycemic activity
      bearing fraction, along with two known compounds, demethoxymatteucinol (1) and
      matteucinol (2). The structures of these isolated compounds were elucidated by
      spectroscopic methods. One of the compounds isolated from CHCl3 extract, 2'
      hydroxymatteucinol (3), showed dose-dependent hypoglycemic activity, and a blood
      sugar lowering effect was observed even at the dose of 10 mg/kg (p.o.) in STZ
      induced diabetic rats.

PMID- 8281577
TI  - Two new quinochalcone yellow pigments from Carthamus tinctorius and Ca2+
      antagonistic activity of tinctormine.
AB  - Two new quinochalcone C-glycosides, hydroxysafflor yellow A (1a) and tinctormine
      (2a), were isolated from Carthamus tinctorius L. (Compositae) together with
      carthamin, safflor yellow B and safflomin C. The structures of 1a and 2a have
      been determined by spectroscopic methods including heteronuclear multiple-bond
      multiple-quantum coherence and linked scan FAB-MS. The latter compound (2a) was
      demonstrated to have potent Ca2+ antagonistic action.

PMID- 8281578
TI  - Isolation and structure of woodorien, a new glucoside having antiviral activity,
      from Woodwardia orientalis.
AB  - Hot aqueous and methanol extracts of the rhizomes of Woodwardia orientalis were
      tested for their in vitro antiviral activity against herpes simplex virus type 1
      (HSV-1), poliovirus type 1, and measles virus by plaque reduction assay. The
      aqueous extract of W. orientalis reduced the plaque forming ability of HSV-1 and
      poliovirus more strongly than did the methanol extract. By bioassay-directed
      fractionation of the aqueous extract, a new glucoside, woodorien (1), along with
      five known compounds were isolated from an EtOAc-soluble fraction that had
      antiviral activity. The structures of these compounds were determined by the use
      of two dimensional (2D) NMR techniques (1H-1H correlation spectroscopy (COSY), 1H
      13C COSY and heteronuclear multiple-bond multiple-quantum coherence (HMBC)).
      Woodorien (1) was the most potent inhibitor against HSV-1 among the isolated
      compounds.

PMID- 8281579
TI  - Design and syntheses of a series of novel serotonin3 antagonists.
AB  - From a structural comparison study between serotonin and serotonin3 (5-HT3)
      antagonists using a two-dimensional grid template composed of regular hexagons,
      we deduced structural modification patterns from agonists to antagonists, and
      designed new 5-HT3 antagonist prototypes. Among them, 2-(4-methyl-1-piperazinyl)
      1-butylbenzimidazole (6) was identified as a lead compound which has potent 5-HT3
      antagonistic activity comparable to that of granisetron. Using a quantitative
      structure-activity relationships method, we optimized the structure of 6 and
      selected 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl)benzimidazole
      dimaleate (69, KB-6933), one of the most potent and long-acting 5-HT3
      antagonists, as a candidate drug.

PMID- 8281580
TI  - Electrochemical oxidation of anti-tumor agent, etoposide.
AB  - As part of a search for new potent derivatives, electrochemical oxidation of
      etoposide (1) was carried out under controlled potential (500 mV) to yield 1,2
      dehydroetoposide (4), 4'-O-demethyl-1,2,3,4-tetradehydro-4-dehydroxy
      podophyllotox in (5) and 1,2,3,4-tetradehydroetoposide (6). They showed no
      cytotoxicity against B16-melanoma.

PMID- 8281581
TI  - Auto-growth inhibitory substance from the fresh-water cyanobacterium Phormidium
      tenue.
AB  - An extract of the cyanobacterium P. tenue showed a significant inhibitory effect
      on its own growth. Bioassay-directed fractionation has led to the identification
      of the auto-growth inhibitory substance as a mixture of fatty acids. Unsaturated
      fatty acids such as linoleic and linolenic acids appear to be predominantly
      responsible for the auto-growth inhibitory effect.

PMID- 8281582
TI  - Dauricoside, a new glycosidal alkaloid having an inhibitory activity against
      blood-platelet aggregation.
AB  - Dauricoside (1), a new glycosidal alkaloid, was isolated from the rhizomes of
      Menispermum dauricum DC. along with dauricine (2), daurisoline (3), dauriporphine
      (4), menisporphine (5), and 6-O-demethylmenisporphine (6), and its structure was
      determined by means of spectroscopic methods. Compounds 1, 2, and 3 inhibited
      blood-platelet aggregation induced by adenosine 5'-diphosphate (ADP).

PMID- 8281583
TI  - Anthraquinones, naphthohydroquinones and naphthohydroquinone dimers from Rubia
      cordifolia and their cytotoxic activity.
AB  - Further investigation of the roots of Rubia cordifolia resulted in the isolation
      of four new naphthohydroquinones and two naphthohydroquinone dimers, and one
      known naphthohydroquinone, one naphthoquinone, two anthraquinones and one
      naphthohydroquinone dimer. The structures of these compounds were established by
      various chemical and spectroscopic methods including two dimensional NMR
      techniques. Also, the isolated compounds were submitted to a bio-assay for
      cytotoxic and antitumor activity.

PMID- 8281584
TI  - Synthesis of biologically active N-acylated L-serine-containing D-glucosamine-4
      phosphate derivatives of lipid A.

PMID- 8281585
TI  - Cardiac anaesthesia: a perspective for the 1990's.

PMID- 8281586
TI  - Health care "reform" and the costs of anaesthesia.

PMID- 8281587
TI  - Ketorolac and indomethacin are equally efficacious for the relief of minor
      postoperative pain.
AB  - Injectable ketorolac is an effective analgesic in ambulatory surgery patients.
      However, no studies have compared ketorolac with other NSAIDs in this setting.
      The analgesic efficacy of intramuscular ketorolac, rectal indomethacin and
      placebo was compared in healthy women undergoing gynaecological or breast surgery
      as outpatients. Ninety patients received 30 mg im ketorolac, 100 mg pr
      indomethacin or placebo in a prospective, randomized, double-blind manner. A
      standardized anaesthetic protocol was followed. Patients graded their pain on a
      10 cm visual analogue scale in the recovery room, twice in the surgical day care
      unit and during the car ride home. The patients' postoperative fentanyl
      requirements, time to recovery milestones, and side effects were recorded. The
      placebo group received more fentanyl in the PACU but did not achieve the same
      pain relief as either of the NSAID-treated group (ketorolac 44 +/- 53 micrograms,
      indomethacin 39 +/- 55 micrograms, placebo 87 +/- 100 micrograms, P < 0.05).
      Patients who received an NSAID had less pain at 15 and 90 min (P < 0.05). The
      PACU stay was longer for the placebo group (ketorolac 50 +/- 13 min, indomethacin
      49 +/- 12 min, placebo 62 +/- 35 min, P < 0.05). Time to ambulation was also
      longer in the placebo group (ketorolac 117 +/- 25 min, indomethacin 121 +/- 49
      min, placebo 140 +/- 51 min, P < 0.05). However, no differences were observed
      between the two NSAIDS. Side effects were similar in all groups. We conclude that
      im ketorolac and pr indomethacin are equally effective analgesics in this group
      of patients.

PMID- 8281588
TI  - Comparison of the 25-gauge Whitacre with the 24-gauge Sprotte spinal needle for
      elective caesarean section: cost implications.
AB  - Spinal anaesthesia provides rapid, safe anaesthesia for Caesarean section. The
      pencil-point spinal needles (Sprotte and Whitacre) are reported to have a low
      incidence of post-dural puncture headache (PDPH). As the 25G Whitacre is less
      expensive than the 24G Sprotte needle, this prospective, randomized, double-blind
      study was designed to compare the incidence of PDPH and ease of insertion of
      these needles in 304 ASA 1 and 2 women having elective Caesarean section under
      spinal anaesthesia. Each patient was assessed daily for five consecutive days
      following Caesarean section by an investigator blinded to the needle used. The
      results indicate that the two needles have a similar ease of insertion, number of
      failed insertions, and failed subarachnoid blockade. An inability to insert the
      spinal needles occurred in two patients in each group. Therefore, 150 patients in
      each group completed the study. The incidence of PDPH with the 24G Sprotte needle
      was 4.0% (6/150) compared with 0.66% (1/150) with the 25G Whitacre (NS). There
      was no correlation between the occurrence of PDPH and the difficulty of needle
      insertion, presence of transient hypotension or the effectiveness of anaesthesia
      delivered. This study indicates that both needles are comparable with respect to
      ease of insertion and incidence of PDPH. As the Whitacre needle is less expensive
      it is a reasonable alternative to the more expensive Sprotte needle.

PMID- 8281589
TI  - Maternal positioning affects fetal heart rate changes after epidural analgesia
      for labour.
AB  - Adverse fetal heart rate (FHR) changes suggestive of fetal hypoxia are seen in
      patients with normal term pregnancies after initiation of epidural block for
      labour analgesia. It was our hypothesis that, in some parturients, these changes
      were a consequence of concealed aortocaval compression resulting in decreased
      uterine blood flow. We expected that the full lateral position compared with the
      wedged supine position would provide more effective prophylaxis against
      aortocaval compression. To test our hypothesis we studied the role of maternal
      positioning on FHR changes during onset of epidural analgesia for labour. Eighty
      eight ASA Class I or II term parturients were randomized into two groups: those
      to be nursed in the wedged supine position and those to be nursed in the full
      lateral position during induction of an epidural block. External FHR monitoring
      was employed to assess the fetal response to initiation of labour epidural
      analgesia. Epidural catheters were sited with the parturients in the sitting
      position and the patients then assumed the study position. After a negative test
      dose, a standardized regimen of bupivacaine 0.25% was employed to provide labour
      analgesia. The quality and efficacy of the block were assessed using VAS pain
      scores, motor block scores and sensory levels. The results demonstrated that
      there was no difference in the quality of analgesia provided nor in the incidence
      of asymmetric blocks. There was no difference in the observed incidence of FHR
      changes occurring during the initiation of the epidural block.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8281590
TI  - Propofol or midazolam for short-term alterations in sedation.
AB  - It is often necessary to adjust a patient's sedation level while they are in the
      intensive care unit. The purpose of this study was to compare propofol with
      midazolam for controlling short-term alterations in sedation. Twenty-three
      patients undergoing an interactive procedure, physiotherapy, during mechanical
      ventilation of the lungs were studied. The patients were randomly assigned to
      receive infusions of propofol or midazolam for sedation. Sedation was assessed
      using the method of Ramsay, where 3 is drowsy responding only to commands; and 5
      is asleep with a slow response to light glabellar tap. Prior to physiotherapy
      sedation was deepened from 3 to 5 by increasing the sedative infusion rate, and
      level 5 was maintained during physiotherapy by adjusting the infusion rate
      whenever necessary. After physiotherapy, the sedative dose was reduced until
      level 3 was again achieved. During physiotherapy, sedation level 5 was achieved
      for 53.9% of the time with propofol but for only 25.7% with midazolam (P < 0.01).
      After physiotherapy, those patients sedated with propofol re-awakened to level 3
      faster (8.3 +/- 2.3 min, mean +/- SE) than those receiving midazolam (92.8 +/-
      35.0 min, P < 0.05). After physiotherapy, a further 1.8 +/- 0.5 dose adjustments
      were required to the midazolam infusion while only 0.4 +/- 0.2 adjustments were
      required to the propofol infusion (P < 0.05). During physiotherapy 3.0 +/- 0.5
      dose adjustments to the propofol dose were required compared with 3.6 +/- 0.5
      adjustments to the midazolam dose (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281591
TI  - Effects of benzodiazepines on mid-latency auditory evoked potentials.
AB  - Midlatency auditory evoked potentials (MLAEP) reflect primary cortical processing
      of auditory stimuli. The effects of benzodiazepines on MLAEP have not yet been
      studied. We examined the effects of intravenous induction of general anaesthesia
      using the benzodiazepines midazolam, diazepam and flunitrazepam on MLAEP in 30
      patients scheduled for minor gynaecological procedures. Anaesthesia was induced
      with midazolam (0.2-0.3 mg.kg-1, Group I, n = 10), diazepam (0.3-0.4 mg.kg-1,
      Group II, n = 10) or flunitrazepam (0.03-0.04 mg.kg-1, Group III, n = 10).
      Auditory-evoked potentials were recorded before and five to ten minutes after
      induction of general anaesthesia. Latencies of the peak V, Na, Pa, Nb and Pl (ms)
      and amplitudes Na/Pa, Pa/Nb and Nb/P1 (microV) were measured. In the awake state,
      MLAEP had high peak to peak amplitudes and a periodic waveform. After induction
      of anaesthesia there was no or only a small increase in latencies of the peaks
      Na, Pa, Nb and P1, which was significant only for P1 in the midazolam group.
      Amplitudes Na/Pa, Pa/Nb and Nb/P1 decreased only slightly and which reached
      statistical significance only for Na/Pa in the flunitrazepam group. The MLAEPs do
      not change markedly in amplitude or latency during induction of general
      anaesthesia with benzodiazepines. Primary cortical processing of auditory stimuli
      seems to be preserved under benzodiazepines. This may be seen in connection with
      cases of intraoperative awareness and especially the perception of auditory
      stimuli during anaesthetic regimens where benzodiazepines are used to suppress
      consciousness.

PMID- 8281592
TI  - A single i.v. dose of ondansetron 8 mg prior to induction of anaesthesia reduces
      postoperative nausea and vomiting in gynaecological patients.
AB  - The effect of a single intravenous dose of ondansetron in preventing
      postoperative nausea and emesis (retching and vomiting) (PONV) was investigated
      in a randomized, double-blind, placebo-controlled, multicentre, international
      study. Women of ASA class I-III, requiring gynaecological laparotomy, vaginal
      hysterectomy, or major vaginal surgery were selected for study. Two hundred and
      thirty-five received placebo, 231 received 1 mg ondansetron, 228 received 8 mg
      ondansetron and 229 received 16 mg ondansetron, as an infusion over five minutes
      before the induction of anaesthesia. A standardized balanced anaesthetic
      technique was employed. This consisted of premedication with either diazepam or
      temazepam, thiopentone induction, maintenance with nitrous oxide in oxygen
      supplemented with enflurane or isoflurane, intraoperative analgesia with
      fentanyl, neuromuscular blockade with any choice of agent and reversal with
      neostigmine and atropine. Postoperative analgesia was achieved with morphine, and
      prochlorperazine or metoclopramide were given if a rescue antiemetic was
      required. A greater percentage of patients in the 8 mg and 16 mg ondansetron
      groups experienced no postoperative emesis (44% and 39% respectively) than in the
      placebo and 1 mg ondansetron groups (29% and 28% respectively) for the first 24
      hr postoperative period (8 mg vs placebo and 1 mg: P < or = 0.001; 16 mg vs
      placebo: P < 0.05; 16 mg vs 1 mg: P < 0.05). Similarly, the percentage of
      patients who did not experience postoperative nausea were 20%, 26%, 31% and 28%
      for the placebo, 1 mg, 8 mg and 16 mg ondansetron treatment groups, respectively
      (8 mg and 16 mg vs placebo P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281593
TI  - Perioperative changes in superoxide production in neonates and infants.
AB  - We conducted a prospective study to investigate perioperative changes in the
      production of superoxide anion (O2-) by neutrophils isolated from ten neonates
      between the ages of five and 16 days (N group) and ten infants ranging in age
      from one to ten months (I group). They underwent abdominal surgery under general
      anaesthesia with halothane and nitrous oxide in oxygen. The O2- production (speed
      and amount) was measured perioperatively using the cytochrome c reduction method.
      Both groups showed a decrease in the speed and amount of O2- production during
      and after surgery. The decrease in O2- production reached its lowest level three
      hours postoperatively or at the end of surgery in both groups. The O2- production
      in the I group returned to the basal value 48 hr postoperatively. In contrast,
      the O2- production in the N group was still lower 48 hr after surgery than before
      anaesthesia. Although the total amount of O2- production by neutrophils in one mL
      of peripheral blood remained unchanged in the I group, the total amount of O2-
      production in the N group decreased at the end of surgery and thereafter. These
      data indicate that even relatively minor abdominal surgery with halothane
      anaesthesia may be associated with perioperative neutrophil impairment in both
      neonates and infants. This impairment of neutrophil function in infants but not
      in neonates may be compensated by an increase in neutrophil numbers. It is
      possible that perioperative susceptibility of neonates to bacterial infections is
      attributable, at least in part, to the inhibition of O2- production in
      neutrophils by surgery and general anaesthesia.

PMID- 8281594
TI  - Anaesthesia for adenotonsillectomy: a comparison between tracheal intubation and
      the armoured laryngeal mask airway.
AB  - A prototype armoured laryngeal mask airway (LMA) was compared with tracheal
      intubation (ETT) for anaesthesia for adenotonsillectomy. Fifty-five children were
      randomised into the LMA group and 54 into the ETT group. During insertion of the
      LMA, peripheral oxyhaemoglobin desaturation (SpO2) < 94% occurred in ten patients
      (18.2%) and in seven patients (13%) during tracheal intubation (NS). After
      opening the Boyle-Davis gag, airway obstruction occurred in ten patients (18.2%)
      in the LMA group and in three patients (6%) in the ETT group (P = 0.07). In five
      patients (9%) the LMA was abandoned in favour of tracheal intubation. In all
      others (91%), when the need for adequate depth of anaesthesia was realized, a
      satisfactory airway was achieved more rapidly than with tracheal intubation (P <
      0.001), and maintained throughout surgery. Manually assisted ventilation was
      required in all patients in the ETT group, mean duration 373 +/- 385 sec, and in
      26 patients (52%) in the LMA group, mean duration 134 +/- 110 sec, P < 0.001.
      Mean end-tidal CO2 (PetCO2) was 45.5 +/- 6.21 mmHg in the ETT group and 46.6 +/-
      6.09 in the LMA group (NS). The LMA did not limit surgical access. Heart rate,
      MAP and blood loss in the LMA group were 110 +/- 21, 74 +/- 9 mmHg and 1.92 +/-
      1.22 ml.kg-1 respectively, compared with 143 +/- 13 (P < 0.001), 85 +/- 12 mmHg
      (P < 0.001) and 2.62 +/- 1.36 ml.kg-1 (P < 0.05) with tracheal intubation.
      Fibreoptic laryngoscopy at the end of surgery in 19 patients in the LMA group
      revealed no blood in the larynx.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281596
TI  - Sevoflurane anaesthesia for one-lung ventilation with PEEP to the dependent lung
      in sheep: effects on right ventricular function and oxygenation.
AB  - This study was undertaken to examine the effect of sevoflurane on right
      ventricular function, the safety of sevoflurane for one-lung ventilation and the
      effects of PEEP (positive end-expiratory pressure) to the dependent lung in this
      model using 12 open-chest sheep. Haemodynamic variables, including cardiac
      output, mean arterial blood pressure, right ventricular pressure and pulmonary
      arterial pressure, and right ventricular segment shortening (sonomicrometry) were
      measured. First, animals received 2.0, 3.0 or 4.0% sevoflurane for 20 min each,
      respectively, during two-lung ventilation to measure the dose-dependent
      haemodynamic effects of sevoflurane. Then one-lung ventilation was performed with
      a randomized sequence of 0 (ZEEP), 5 and 10 cm H2O PEEP to the dependent lung
      under 2.0% sevoflurane anaesthesia after one-hour stabilization. A decrease in
      systolic segment shortening along with increases in both the end-diastolic and
      end-systolic lengths of the right ventricle were observed at 3.0 and 4.0%
      sevoflurane, while global right ventricular function remained substantially
      unchanged during two-lung ventilation. During one-lung ventilation the PaO2 was
      greater with 5 cm H2O PEEP 198 mmHg (+/- 25 SEM) than with ZEEP 138 mmHg (+/- 22)
      or with 10 cm H2O PEEP 153 mmHg (+/- 23) (P < 0.05). No differences in
      haemodynamic variables or segment shortening between ZEEP and PEEPs during one
      lung ventilation were observed. We conclude that although sevoflurane causes a
      dose-dependent depression of right ventricular function, sevoflurane anaesthesia
      can be safely applied to one-lung ventilation, and that 5 cm H2O PEEP to the
      dependent lung can improve arterial oxygenation without causing changes in right
      ventricular function.

PMID- 8281597
TI  - Plasma concentrations of bupivacaine after brachial plexus administration of
      liposome-associated and plain solutions to rabbits.
AB  - Bupivacaine has been associated to multilamellar liposomes with the aim of
      altering circulating plasma concentrations after injection into the rabbit
      brachial plexus. Plasma concentrations of bupivacaine have been compared after
      administration of free drug (BP) or bupivacaine associated to multilamellar
      liposomes (BP-MLV) made of phosphatidylcholine and cholesterol (molar ratio 4:3).
      Under light general anaesthesia, one group of six rabbits received an axillary
      injection of 2.5 mg BP (1 ml, 0.25%), and a second received the same dose of BP
      MLV. In both groups 3H bupivacaine was used as a marker. The brachial plexus was
      located using a nerve stimulator. Injection of the anaesthetic solutions
      invariably prevented the motor response of the paw. The arterial plasma
      concentrations of bupivacaine were determined after 5 to 240 min and after 24 hr
      by beta counting. In the MLV population, additional measurements were performed
      after 48 and 72 hr. The two plasma curves showed a plateau (0.2 microgram.ml-1)
      which was reached after five minutes in the BP group and after 90 min using BP
      MLV. In the BP-MLV group, the plasma concentrations of bupivacaine were lower
      during the first ten minutes (P < 0.05), and higher after 24 hr (P < 0.05).
      Radioactivity decreased between 4 and 24 hr in the BP group and between one and
      two days in the BP-MLV population. It is concluded that elevated plasma drug
      concentrations were maintained for longer with BP-MLV than with BP. This could
      prolong the action of the local anaesthetic through a slow release.

PMID- 8281599
TI  - [Fernando Hudon (1907-1982)].

PMID- 8281595
TI  - Anaesthesia for coronary artery surgery--a plea for a goal-directed approach.
AB  - The purpose of the current literature review was to examine whether changes in
      current anaesthetic techniques are warranted for patients undergoing coronary
      artery surgery in light of recent information presented in the literature. The
      objectives of a cardiac anaesthetic technique are to maintain haemodynamic
      stability and myocardial oxygen balance, minimize the incidence and severity of
      ischaemic episodes, be aware of cardiopulmonary bypass-induced pharmacokinetic
      changes, and facilitate early tracheal extubation if appropriate. Many techniques
      have been utilized. Provided attention is paid to the details of managing
      myocardial oxygen supply and demand, none has emerged as superior in preventing
      intraoperative myocardial ischaemia. Silent myocardial ischaemia (i.e., ischaemia
      occurring in the absence of haemodynamic aberrations) is common throughout the
      perioperative period and may occur even in the presence of an appropriately used
      anaesthetic technique. The incidence and severity appear to be greatest in the
      postoperative period when the effects of anaesthesia are dissipating. The use of
      high-dose opioid anaesthesia may no longer be the most appropriate technique to
      facilitate the anaesthetic objectives. The role of pain management in altering
      the incidence of ischaemia requires further study. Increased waiting lists for
      cardiac surgery and ever-diminishing resources should prompt a re-evaluation of
      early extubation (i.e., within eight hours) as a method of improving utilization
      of scarce ICU resources. It is suggested that this should be possible with
      currently available agents to achieve the anaesthetic objectives. Future
      suggestions for research in this area are made.

PMID- 8281598
TI  - Clonidine does not affect lidocaine seizure threshold in rats.
AB  - We investigated the effect of clonidine on intravenous (i.v.) lidocaine-induced
      haemodynamic changes and convulsions in awake rats. Wistar rats (200-250 g) were
      divided into three groups of eight and were pretreated with i.v. clonidine or
      normal saline 15 min before lidocaine infusion. Group 1 received normal saline;
      Group 2, 1 microgram.kg-1 clonidine; and Group 3, 10 micrograms.kg-1 clonidine.
      After surgical preparation and recovery from anaesthesia, all groups received a
      continuous i.v. infusion of lidocaine (15 mg.ml-1) at a rate of 4 mg.kg-1.min-1
      until generalized convulsions occurred. Oxygenation was well maintained in all
      groups. Pretreatment with clonidine changed neither cumulative convulsant doses
      (Group 1: 41.8 +/- 2.2, Group 2: 43.8 +/- 2.6, Group 3: 42.3 +/- 2.0 mg.kg-1,
      respectively) nor plasma concentrations of lidocaine at the onset of convulsions
      (Group 1: 10.5 +/- 0.3, Group 2: 10.8 +/- 0.3, Group 3: 10.6 +/- 0.3
      micrograms.ml-1, respectively). The mean arterial blood pressures in Groups 2 and
      3 were decreased after clonidine pretreatment (Group 2: 93 +/- 1, P < 0.01, Group
      3: 90 +/- 1%, P < 0.01, respectively) and they gradually increased during
      lidocaine infusion. The heart rates decreased after clonidine pretreatment (Group
      2: 94 +/- 2, P < 0.05, Group 3: 86 +/- 2%, P < 0.01, respectively) and the
      combination of clonidine and lidocaine potentiated the bradycardic effect of
      lidocaine at a subconvulsant dose. Our results indicate that clonidine has
      neither anticonvulsant nor proconvulsant effects on lidocaine-induced
      convulsions. However, the interactions of clonidine and lidocaine on blood
      pressure and heart rate should be investigated further.

PMID- 8281600
TI  - Refractoriness of neuromuscular transmission: determination by computer
      subtraction of neurally evoked compound electromyograms.
AB  - Shortly after elicitation of a muscle response by supramaximal stimulation of its
      motor nerve, there exists a period of refractoriness of neuromuscular
      transmission when a second stimulation elicits only a submaximal response or no
      response at all. Many anaesthetics and neuromuscular blocking and facilitatory
      drugs change the refractoriness of neuromuscular transmission. Measurement of
      this refractoriness may improve our understanding of the neuromuscular actions of
      these drugs and be useful in differential diagnosis. However, the neuromuscular
      refractory periods (RP) are difficult to measure, and the unavailability of
      normal values renders accurate determination of drug effects impossible. Based on
      an existing technique of digitization and time expansion of the neurally evoked
      compound electromyogram (ncEMG), we developed a computer programme of waveform
      subtraction, and determined in nine normal awake volunteers the various
      interstimulus intervals when neuromuscular transmission was refractory (RP0), 3/4
      refractory (RP.25), half refractory (RP.5), 1/4 refractory (RP.75) or non
      refractory (RP1). We confirmed our hypotheses that computer-based waveform
      subtraction of the digitized ncEMG is a feasible and necessary technique for the
      accurate determination of the RPs of neuromuscular transmission, and report that
      the normal values in humans are: RP0 = 1.0 +/- 0.1, RP.25 = 1.3 +/- 0.3, RP.5 =
      1.9 +/- 0.3, RP.75 = 2.9 +/- 0.5, and RP1 = 6.6 +/- 1.9 ms (mean +/- SD),
      respectively, in the ulnar nerve-first dorsal interosseous muscle model.

PMID- 8281601
TI  - Modified retrobulbar block.

PMID- 8281602
TI  - Confirmation of internal jugular vein cannulation: the Finucane technique.

PMID- 8281603
TI  - Elective use of the laryngeal mask in patients with difficult airways.

PMID- 8281604
TI  - The laryngeal mask airway in awake patients.

PMID- 8281605
TI  - The Combitube oesophageal-tracheal double lumen airway for difficult intubation.

PMID- 8281606
TI  - Bronchial blockade to improve alveolar ventilation.

PMID- 8281607
TI  - Acupuncture accelerates recovery from general anaesthesia.

PMID- 8281608
TI  - Polamedco endotracheal tubes.

PMID- 8281609
TI  - Growth factor independence and growth regulatory pathways in human melanoma
      development.
AB  - This review concentrates on growth autonomy of tumor cells in relation to tumor
      progression. Human malignant melanoma serves as an example for progressive growth
      factor independence at subsequent stages of tumor progression. Mechanisms by
      which malignant cells acquire growth factor independence are discussed. In
      melanoma, deregulation of growth regulatory pathways has been described on four
      levels: 1) aberrant production of autocrine growth factors that substitute for
      exogenous growth factors (basic fibroblast growth factor [bFGF]); 2) alterations
      in the response to negative autocrine growth factors (interleukin [IL]-6 and
      transforming growth factor [TGF]-beta); 3) overexpression of epidermal growth
      factor receptors (EGF-R); and 4) alterations of cellular protooncogenes involved
      in signal transduction (RAS, MYB) and growth suppression (p53). In addition to
      bFGF and IL-6, multiple other growth factor genes are activated in malignant
      melanoma cells but not normal melanocytes. These include both chains of platelet
      derived growth factor (PDGF), TGF-alpha, IL-1, IL-8, and tumor necrosis factor
      (TNF)-alpha. Of these, PDGF-B has been investigated in more detail. Melanoma
      derived PDGF clearly does not act in a direct autocrine mode, but has important
      paracrine effects on normal tissue constituents, notably fibroblasts and
      endothelial cells, that are essential for tumor development in vivo. It is
      speculated that other melanoma-derived growth factors with as yet undefined
      functions similarly exert such paracrine or 'indirect' autocrine effects that
      cannot be sufficiently addressed in studies on cultured cells.

PMID- 8281610
TI  - Escape from negative regulation of growth by transforming growth factor beta and
      from the induction of apoptosis by the dietary agent sodium butyrate may be
      important in colorectal carcinogenesis.
AB  - There are a number of lines of evidence suggesting that transforming growth
      factor beta (TGF beta) has an important role in the control of intestinal growth
      and differentiation. In vivo localization studies show that TGF beta expression
      occurs predominantly in the differentiated non proliferating cells of the
      intestinal epithelium. The use of an antisense expression vector for TGF beta
      resulted in an increased tumorigenicity in an antisense-transfected cancer cell
      line. In vitro proliferation studies showed colorectal premalignant adenoma cells
      to be more sensitive to the growth inhibitory effects of TGF beta than colorectal
      cancer cells. Furthermore the conversion of an adenoma to a carcinoma was
      accompanied by a reduced response to the inhibitory effects of TGF beta. The
      acquisition of partial or complete resistance to the inhibitory effects of TGF
      beta may be an important late event in colorectal carcinogenesis. Of further
      interest is the possibility that clonal selection could occur even more rapidly
      in colorectal tumour cells which not only had lost response to TGF beta
      inhibition but produced TGF beta and were growth stimulated by it. This could
      have the advantage of not only inhibiting the growth of surrounding less
      malignantly advanced cells but of also escaping from their potential growth
      suppressive influence. Carcinogenesis is not, however, simply losing response to
      negative regulators of growth; the fully malignant cell has to acquire new
      characteristics of invasiveness and metastatic potential. Growth factors
      including TGF beta may have a role in the complex cascade of events leading to
      the activation of proteolytic enzymes which are involved in progression to an
      invasive phenotype. Cell proliferation in the large bowel, as well as being under
      the control of endogenous growth factors, is also under the influence of dietary
      components in the lumen such as the naturally occurring fatty acid sodium
      butyrate. Sodium butyrate at physiological concentrations induces apoptosis
      (programmed cell death) in colonic tumour cell lines. Since sodium butyrate
      occurs naturally in the colorectum, being produced by bacterial fermentation of
      dietary fibre, it may be involved in the control of cell death in human
      colorectal epithelium. This could, in part, explain the apparent protective
      effects of dietary fibre. Clonal evolution and tumour progression in colorectal
      carcinogenesis could therefore involve loss of response to endogenous growth
      factors such as TGF beta and an escape from the induction of programmed cell
      death by dietary factors.

PMID- 8281611
TI  - Transforming growth factor beta and the cell surface in tumor progression.
AB  - Type 1 transforming growth beta (TGF-beta 1) is a multifunctional regulator of
      cellular differentiation, motility and growth. It is capable of inhibiting or
      stimulating these processes depending on cell type, cell density, culture
      conditions and TGF-beta 1 concentration. TGF-beta 1 regulates growth, in part, by
      inducing the expression and secretion of various types of collagen, which
      participate in the control of cell adhesion and migration, as well as growth. TGF
      beta 1 also regulates cell growth by controlling the response to epidermal growth
      factor (EGF) and other growth factors, in ways that can either decrease or
      increase their growth-promoting effects. Alterations in both negative and
      positive growth responses to TGF-beta 1 play important roles in tumor
      progression. Loss of sensitivity to growth inhibition by TGF-beta 1 can occur as
      a result of decreased expression of collagen. Acquisition of sensitivity to
      growth stimulation, and autocrine transformation by TGF-beta 1, are associated
      with aberrant EGF receptor regulation. Aberrant growth factor receptor regulation
      by TGF-beta 1 may be mediated by a protein kinase C (PKC)-dependent pathway which
      inhibits degradation of growth factor receptor/ligand complexes. The evidence
      reviewed is consistent with a minimal two-step mechanism for autocrine
      transformation, which involves production of growth factor and enhanced cellular
      response as a result of aberrant membrane traffic. Defects in membrane traffic
      regulation may provide an explanation for common alterations in tumor cell
      response to both multiple growth inhibitors and growth stimulators, and may also
      suggest novel approaches to cancer chemotherapy.

PMID- 8281613
TI  - The role of growth regulatory aberrations in progression of human colon
      carcinoma.
AB  - Colon carcinoma is a multistage disease. Most malignancies arise from pre
      existing benign tumors. Multiple chromosomal defects affecting oncogene and tumor
      suppressor gene function are associated with disease progression. These
      aberrations result in an imbalance between the normal positive and negative
      growth effectors, which contribute further to disease progression. We have
      studied how changes in the expression of TGF alpha and TGF beta affect colon
      carcinoma cell behavior. Overexpression of the stimulatory factor TGF alpha in a
      relatively benign cell line with weak TGF alpha autocrine activity converted the
      cell type to an aggressive, progressed phenotype in vivo and in vitro. In
      contrast, disruption of TGF alpha expression by constitutive expression of TGF
      alpha antisense RNA in a progressed cell line with a strong, internalized
      autocrine loop resulted in the development of clones with decreased
      tumorigenicity in vitro and in vivo. Suppression of the inhibitory effects of TGF
      beta by constitutive expression of TGF beta antisense RNA increased the
      tumorigenicity of the cell lines in vitro and in vivo. None of these alterations
      in TGF alpha or TGF beta expression affected the doubling time of the cells. The
      changes in tumorigenicity were due to effects on the lag phase of growth. We
      conclude that TGF beta functions to maintain the cells in a quiescent state while
      TGF alpha drives reentry into the cell cycle. We have identified a unique cis
      element that mediates TGF alpha autoregulation. The transcription factor binding
      this element is also involved in the cell-cycle regulation of TGF alpha
      expression. We hypothesize that this factor may be a convergent point TGF alpha
      and TGF beta interact in controlling movement into and out of quiescence.

PMID- 8281612
TI  - EGF receptor in neoplasia and metastasis.
AB  - EGFR is a member of the tyrosine kinase family of cell surface receptors with a
      wide range of expression throughout development and in a variety of different
      cell types. The receptor can transmit signals to cells: i) upon interaction with
      ligands such as EGF, TGF alpha, amphiregulin or heparin binding EGF, ii) upon
      truncation or mutation of extracellular and/or intracellular domains, iii) upon
      amplification of a basal receptor activity (in the absence of ligand) through
      cooperation with other cellular signaling pathways or nuclear events (e.g.
      expression of v-erbA). The activated EGFR can exert pleiotropic functions on
      cells, depending on their tissue origin and state of differentiation. Under
      certain conditions it can also contribute to neoplasia and development of
      metastases. Such conditions can exist upon aberrant receptor/ligand expression
      and activation (e.g. in the wrong cell; at the wrong time; in the wrong amounts).
      Aberrant signalling can also occur through constitutive EGFR activation.
      Oncogenic potential of EGFR has been demonstrated in a wide range of experimental
      animals. EGFR is also implicated in human cancer, where it may contribute both to
      the initiation (glioblastoma) and progression (epithelial tumors) of the disease.
      EGFR may influence key steps in the processes of tumor invasion and
      dissemination. Involvement of EGFR in tumor spread may indicate a potential use
      of this receptor as a target for antimetastatic therapy.

PMID- 8281614
TI  - Growth factors and their receptors as determinants in the proliferation and
      metastasis of human prostate cancer.
AB  - Prostate adenocarcinoma, the most common tumor occurring among North American
      men, preferentially metastasizes to bone, where it characteristically forms
      osteoblastic lesions. The following growth regulatory factors are expressed in
      some human prostate cancers and/or established cell lines: epidermal growth
      factor (EGF), transforming growth factor alpha, transforming growth factor beta,
      basic fibroblast growth factor (bFGF), and insulin-like growth factor. Some of
      these, especially EGF, bFGF, and TGF-beta, are also implicated in growth
      regulation in normal and benign hyperplastic prostates. Although evidence from in
      vitro study of the small number of prostate cell lines available demonstrates
      that these growth regulatory pathways are exploited by some of these cells,
      direct in vivo evidence is limited. The development of human prostate cancer cell
      lines which grow and metastasize in immune-deficient rodents is an advance which
      now permits experimental analysis of the role of these growth factors in
      prostatic metastasis, particularly to bone. The progression and metastasis of
      human prostate cancer results from the complex interactions of multiple growth
      factors, androgens, and cellular communication, which form a dynamic network.
      Continued progress in the study and treatment of this disease will require new
      conceptual frameworks as well as successful application of the techniques of
      molecular and cellular biology.

PMID- 8281615
TI  - Vascular permeability factor (VPF, VEGF) in tumor biology.
AB  - Vascular permeability factor (VPF), also known as vascular endothelial growth
      factor (VEGF), is a multifunctional cytokine expressed and secreted at high
      levels by many tumor cells of animal and human origin. As secreted by tumor
      cells, VPF/VEGF is a 34-42 kDa heparin-binding, dimeric, disulfide-bonded
      glycoprotein that acts directly on endothelial cells (EC) by way of specific
      receptors to activate phospholipase C and induce [Ca2+]i transients. Two high
      affinity VPF/VEGF receptors, both tyrosine kinases, have thus far been described.
      VPF/VEGF is likely to have a number of important roles in tumor biology related,
      but not limited to, the process of tumor angiogenesis. As a potent permeability
      factor, VPF/VEGF promotes extravasation of plasma fibrinogen, leading to fibrin
      deposition which alters the tumor extracellular matrix. This matrix promotes the
      ingrowth of macrophages, fibroblasts, and endothelial cells. Moreover, VPF/VEGF
      is a selective endothelial cell (EC) growth factor in vitro, and it presumably
      stimulates EC proliferation in vivo. Furthermore, VPF/VEGF has been found in
      animal and human tumor effusions by immunoassay and by functional assays and very
      likely accounts for the induction of malignant ascites. In addition to its role
      in tumors, VPF/VEGF has recently been found to have a role in wound healing and
      its expression by activated macrophages suggests that it probably also
      participates in certain types of chronic inflammation. VPF/VEGF is expressed in
      normal development and in certain normal adult organs, notably kidney, heart,
      adrenal gland and lung. Its functions in normal adult tissues are under
      investigation.

PMID- 8281616
TI  - Paracrine and autocrine growth mechanisms in tumor metastasis to specific sites
      with particular emphasis on brain and lung metastasis.
AB  - Once metastatic cells successfully seed at distant sites, their clinical
      detection and danger to the host are dependent on growth to form gross
      metastases. Metastatic tumor cells proliferate in response to local paracrine
      growth factors and inhibitors, and their growth also depends on production and
      responses to autocrine growth factors. A major organ-derived (paracrine) growth
      factor from lung tissue-conditioned medium has been isolated that differentially
      stimulates the growth of cells metastatic to brain or lung. Characterization of
      this mitogen demonstrated that it is a transferrin or a transferrin-like
      glycoprotein. Furthermore, antibodies to transferrin can remove significant
      growth activity from lung tissue-conditioned medium. Cells that are metastatic to
      brain or lung express greater numbers of transferrin receptors on their surfaces
      than cells that are poorly metastatic or metastatic to liver. Growth responses of
      metastatic cells and organ preferences of colonization appear to change during
      progression to more malignant states. At early stages of metastatic progression
      there is a tendency for many common malignancies to metastasize and grow
      preferentially at particular sites, suggesting that paracrine growth mechanisms
      may dominate the growth signals at this stage of progression. In contrast, at
      later stages of metastatic progression widespread dissemination to various
      tissues and organs occurs, and autocrine growth mechanisms may dominate the
      growth responses of metastatic cells. Ultimately, the progression of malignant
      cells to completely autonomous (acrine) states can occur, and at this stage of
      metastatic progression cell growth may be completely independent of autocrine and
      paracrine growth factors or inhibitors.

PMID- 8281617
TI  - Paracrine growth regulation of human colon carcinoma organ-specific metastasis.
AB  - The process of cancer metastasis consists of a series of steps resulting in the
      spread of malignant cells beyond the site of origin and formation of metastases
      in distant organs. The outcome of this nonrandom process depends, in part, on the
      interaction of unique tumor cells with a compatible organ microenvironment. The
      molecular basis of the intrinsic capacity of distinct malignant cells to colonize
      specific organs and the degree to which host factors influence this process is
      under intense investigation. Biological analyses of human colon carcinoma tumors
      obtained from surgical specimens and implanted orthotopically into athymic nude
      mice revealed that these tumors are heterogeneous for metastatic properties.
      Moreover, recent evidence using this model suggest that whereas nonmetastatic and
      highly metastatic cells can grow at local sites, growth in the secondary liver
      specific site was associated only with highly metastatic HCC cells. These cells
      also respond to mitogenic signals produced by damaged normal tissues, suggesting
      that physiological signals can be utilized by neoplastic cells. Molecular
      characterization of highly metastatic HCC cells selected in the nude mouse model
      as well as in situ mRNA hybridization of archival HCC surgical specimens for
      specific growth factor receptors correlated with the malignant cell's ability to
      respond to organ-specific growth factors. This article will focus on biological
      and molecular evidence supporting the hypothesis that organ-derived, paracrine
      growth factors regulate the site-specific growth of receptive malignant cells
      that possess the appropriate receptors.

PMID- 8281618
TI  - Evaluation of a novel bis-naphthalimide anticancer agent, DMP 840, against human
      xenografts derived from adult, juvenile, and pediatric cancers.
AB  - The new bis-naphthalimide antitumor agent (R,R)2,2'-[1,2-ethanediylbis[imino(1
      methyl-2.1-ethanediyl)]-bis(5 -nitro 1H-benz[de]-isoquinoline-1,3-2H) dione]
      dimethanesulfonate (DMP 840) was evaluated against parental and multidrug
      resistant human KB cell lines in vitro and against these lines growing as
      xenografts in immune-deprived mice. In vitro, KB8-5 cells were 50-fold resistant
      to vincristine but only 16-fold resistant to DMP 840 as measured by clonogenic
      survival. For in vivo evaluation, DMP 840 was given by i.v. injection daily for 9
      days or for 5 days/week for 2 consecutive weeks [(dx5)2]. In contrast to the
      cross-resistance of KB cell lines in vitro, both KB3-1 and KB8-5 tumors were
      highly and equally sensitive to DMP 840; only KB3-1 xenografts demonstrated
      sensitivity to vincristine, which was consistent with the in vitro results. DMP
      840 was also evaluated against a panel of human tumors comprising colon
      adenocarcinoma and rhabdomyosarcoma xenografts. Against eight lines of colon
      adenocarcinoma, DMP 840 caused a high frequency of partial and complete
      regressions in two lines and significant inhibition of growth in two lines. DMP
      840 caused complete regressions in five of six lines of advanced
      rhabdomyosarcomas, demonstrating a broad range of effective dose levels. The
      pattern of activity against this tumor panel was similar but not identical to
      that of two inhibitors of topoisomerase I. There was no cross-resistance to DMP
      840 in xenografts selected for resistance to vincristine or in a rhabdomyosarcoma
      selected for resistance to the topoisomerase I inhibitor topotecan. In contrast,
      a colon tumor selected for topotecan resistance was completely resistant to DMP
      840. Slight cross-resistance to DMP 840 was demonstrated in a rhabdomyosarcoma
      xenograft that was selected for primary resistance to melphalan and was cross
      resistant to topoisomerase I inhibitors. The pattern of activity and cross
      resistance in these tumors was compared with that shown by two agents that
      inhibit topoisomerase I: topotecan and CPT-11.

PMID- 8281620
TI  - Effective combination therapy of metastatic murine solid tumors with edatrexate
      and the vinca alkaloids, vinblastine, navelbine and vindesine.
AB  - Studies are described in which a new folate analogue, edatrexate (EDX), in
      combination with the vinca alkaloids, vinblastine (VBL), navelbine (NVB) or
      vindesine (DVA) was evaluated against E0771 mammary adenocarcinoma, T241
      fibrosarcoma and the Lewis lung tumor. Each of the four agents when given
      individually to animals 3 days after transplant of these tumors resulted in
      increases in survival of 53-143%. The relative effectiveness of these agents was
      (in increasing order) VBL, NVB congruent to DVA, EDX, with no long-term survivors
      obtained with any. Combination therapy with EDX and vinca alkaloids required
      dosage attenuation but was still markedly more effective. Treatment of E0771 and
      T241 tumors with EDX and either NVB or DVA increased survival 3- to 4-fold
      compared with therapy with individual agents and yielded 40-70% long-term
      survivors, while EDX with VBL increased survival 2- to 3-fold and yielded 20-40%
      long-term survivors. Simultaneous or sequential (EDX given 24 h before vinca
      alkaloid) administration of combined therapy was equally effective. Sequential
      administration of these agents at the same doses in the reverse order was highly
      toxic and required further dosage attenuation which compromised efficacy. Effects
      of these combinations against the Lewis Lung tumor were not as pronounced and
      were somewhat schedule-dependent. Simultaneous administration of EDX with VBL,
      NVB or DVA increased survival 2- to 3-fold over that obtained with single agents
      alone and yielded 10-40% long-term survivors, while sequential administration
      increased survival < 2-fold over that obtained with single agents and yielded 0
      20% long-term survivors. These results suggest that combined therapy with these
      agents in patients may have appreciable utility and provide a basis for further
      clinical trials.

PMID- 8281619
TI  - Combined oral administration of etoposide and arabinofuranosylcytosine-5'
      stearylphosphate enhances the antitumor effect against P388 ascites tumors.
AB  - We investigated the antitumor effect of oral administration of etoposide and
      arabinofuranosylcytosine-5'-stearylphosphate (C18PCA) against P388 ascites tumors
      in B6D2F1 mice. Etoposide (25 mg/kg) and C18PCA (5 mg/kg) were given orally on
      days 1-5 after tumor inoculation. The median life span of the mice treated with
      etoposide or C18PCA alone was 19.5 and 18 days, respectively. The combination of
      both drugs significantly extended the median life span to 33 days. To clarify
      this enhancement of the increase in median life span, we examined intracellular
      deoxyribonucleoside triphosphate (dNTP) pools, cell-cycle distribution, DNA
      fragmentation, and the time course of the plasma drug concentration. Etoposide
      had no effect on intracellular dNTP pools in this experimental system, whereas
      treatment of cells with C18PCA or with the combination of both drugs resulted in
      a significant increase in dTTP pools to values ranging from 1.8- to 2.0-fold
      higher than the control levels. There was a significant increase in cells in the
      S + G2/M phase when cells had been treated with both etoposide and C18PCA.
      Agarose-gel electrophoresis of the extracted DNA revealed that C18PCA enhanced
      the fragmentation of DNA, with a length of about 180 bp being induced by
      etoposide. The plasma peak levels of etoposide (1000 nM) and ara-C (50 nM) were
      observed at 20 and 30 min after the simultaneous administration of both drugs,
      respectively. The plasma etoposide level gradually decreased to 10% of the peak
      level at 240 min after administration. On the other hand, the plasma
      concentration of ara-C was maintained at above 20 nM at 240 min. These
      observations suggest that C18PCA and etoposide act on P388 murine leukemic cells
      by accumulating cells in the S + G2/M phase. Even if the plasma concentration of
      ara-C is low, the repair of DNA damage by etoposide may be hindered in the
      presence of ara-C following an increase in DNA fragmentation.

PMID- 8281621
TI  - Potentiation of cytotoxicity of mitomycin C by a polyacetylenic alcohol,
      panaxytriol.
AB  - Polyacetylenic alcohol, panaxytriol, which was isolated from Panax ginseng C. A.
      Meyer, has antiproliferative activity against several kinds of tumor cells. In
      this paper, the effect of panaxytriol on the cytotoxicity of mitomycin C (MMC)
      against a human gastric carcinoma cell line, MK-1, was investigated. The
      combination of a subthreshold concentration of MMC and panaxytriol produced a
      significant cytotoxic effect, which indicates that the effects of panaxytriol and
      MMC are synergistic. A synergistic effect was observed when MK-1 cells were
      treated with the mixture of MMC and panaxytriol or treated with MMC followed by
      panaxytriol. In contrast, when MK-1 cells were exposed to panaxytriol and then to
      MMC, only an additive effect was induced. With the aim of finding a possible
      mechanism, the effect of panaxytriol on the accumulation of MMC into the MK-1
      cells was examined. Cellular concentrations of MMC were measured by high
      performance liquid chromatography (HPLC). When MK-1 cells were treated with a
      mixture of panaxytriol and MMC or first with MMC and then with panaxytriol, the
      cellular level of MMC was significantly higher than that in MK-1 cells treated
      with MMC alone, but no significantly increased accumulation was found when MK-1
      cells were treated with panaxytriol followed by MMC. These results suggest that
      synergistic effects of panaxytriol and MMC may be induced by acceleration of the
      effect of MMC on cellular accumulation by panaxytriol. In addition, they suggest
      that the enhanced accumulation of MMC in MK-1 cells treated with panaxytriol can
      probably be attributed to the decreased fluidity of the cell membrane caused by
      panaxytriol.

PMID- 8281622
TI  - An open, randomized study to compare the efficacy and tolerability of tropisetron
      with that of a metoclopramide-containing antiemetic cocktail in the prevention of
      cisplatin-induced emesis.
AB  - In a prospective randomized study comprising 66 women treated for gynecologic
      malignancies with cisplatin-containing chemotherapy, the new 5-hydroxytryptamine3
      (5-HT3) receptor antagonist tropisetron (Navoban, Sandoz Pharma Ltd.) was
      compared with a metoclopramide cocktail for the prevention of nausea and emesis.
      All patients were chemotherapy-naive. Two consecutive courses (including the 1st
      week posttherapy) were studied. The cisplatin doses were in the range of 50-75
      mg/m2, and the regimens also contained doxorubicin, teniposide, etoposide,
      vincristine, and bleomycin. Complete protection against nausea during the first
      24 h (course 1) was achieved in 76% of the tropisetron group and in 85% of the
      metoclopramide group. Emesis was prevented in 82% of the patients in both groups.
      During the whole 6-day period, full emetic protection was achieved in 30% and 18%
      of the patients in the two groups. On days 3-4 of course 1, tropisetron was
      superior to metoclopramide. The overall tolerability of the tropisetron was
      excellent or good in 94% of patients, a rate higher than that observed for the
      metoclopramide regimen (75%). The most common side effects for the latter regimen
      were sedation (82%) and extrapyramidal reactions (21%). The only significant
      adverse event recorded after treatment with tropisetron was headache of slight or
      moderate grade.

PMID- 8281623
TI  - An extended-release formulation of methotrexate for subcutaneous administration.
AB  - Methotrexate is a cell-cycle phase-specific antimetabolite that requires
      prolonged exposure for optimal efficacy. However, the in vivo half-life is short,
      and repeated administrations are required for optimal efficacy. Methotrexate was
      encapsulated into a lipid-based drug-delivery system to create an extended
      release formulation (Depo/methotrexate) for subcutaneous administration.
      Pharmacokinetics and efficacy studies were done in BDF1 mice. Depo/methotrexate
      increased the methotrexate plasma half-life by a factor of 190, from 0.53 to 100
      h. Plasma peak levels of the encapsulated drug were 120-fold lower than those of
      unencapsulated methotrexate, whereas the AUCs (areas under the concentration-time
      curve) were similar. As a consequence of the extended drug release, the single
      dose potency of methotrexate against the L1210 leukemia model was increased by a
      factor of about 130 without producing significant changes in the therapeutic
      index. In conclusion, Depo/methotrexate appears to have potential usefulness as
      an extended-release formulation of methotrexate.

PMID- 8281624
TI  - Combination chemotherapy of human ovarian xenografts with intraperitoneal
      liposome-incorporated valinomycin and cis-diamminedichloroplatinum(II).
AB  - Intraperitoneal administration of liposomal valinomycin (MLV-VM) with cis
      diamminedichloroplatinum(II) (cDDP) had significant antitumor activity against
      murine P388 leukemia and inhibited the growth of OVCAR-3 tumors in a nude mouse
      model of human ovarian cancer. This tumor is a teratoma originating in the ovary
      with pathogenesis and metastatic properties similar to those of human ovarian
      cancer. Drug was given to the mice once every 5 days for 4 doses beginning 1 day
      after i.p. implantation of 10(7) or 5 x 10(7) OVCAR-3 tumor cells. For P388
      leukemia, drug was given i.p. once or on days 1 and 5 after tumor inoculation.
      Despite the use of low doses of MLV-VM, the antitumor activity of the combination
      [increase in life span (%T/C), 289%-294%] represents a 4-log cell kill over the
      additive effect of the two drugs, indicating a synergistic interaction between
      MLV-VM and cDDP. Likewise, low doses of the drug combination produced a
      synergistic interaction on human ovarian OVCAR-3 tumors, and tumor-free, long
      term survivors were obtained. Combined therapy of liposome-incorporated
      valinomycin and cisplatin was well tolerated and produced no overlapping
      nephrotoxicity, although a decrease in liver enzyme markers (alkaline phosphatase
      and/or alkaline aminotransferase) with MLV-VM was observed. These results appear
      to suggest that MLV-VM with cDDP may have considerable potential for the
      treatment of ovarian cancer disseminated within the peritoneal cavity, although
      the frequency and sequence of drug administration may need to be improved.

PMID- 8281625
TI  - Phase I trial of droloxifene in patients with metastatic breast cancer.
AB  - Droloxifene (3-hydroxytamoxifen) is a new, nonsteroidal antiestrogen. In
      comparison with tamoxifen, it has a 10- to 64-fold higher affinity for the
      estrogen receptor and has shown a lower estrogenic and higher antiestrogenic
      effect in experimental studies. The objective of this study was to determine the
      toxicity (and its reversibility) of droloxifene given at different doses to
      patients with advanced metastatic breast cancer refractory to conventional
      endocrine therapy and chemotherapy. In this study, 30 patients were treated in
      groups of 6 at 5 different doses (20, 40, 100, 200, and 300 mg) by mouth once a
      day. Toxic effects included hot flashes, nausea, and fatigue and were not dose
      related. Toxicity did not require any dose reduction or discontinuation of
      therapy. There was one episode of deep venous thrombosis and pulmonary embolism.
      There was no complete or partial response in this study, but four patients showed
      a minor response (13%). These data illustrate that this drug is well tolerated
      and needs to be further evaluated in phase II and III studies.

PMID- 8281626
TI  - Differential effectiveness of a range of novel drug-resistance modulators,
      relative to verapamil, in influencing vinblastine or teniposide cytotoxicity in
      human lymphoblastoid CCRF-CEM sublines expressing classic or atypical multidrug
      resistance.
AB  - A series of five potential modulators of resistance were tested for their
      relative ability, as compared with verapamil, to sensitize CEM lymphoblastoid
      leukemia drug-resistant tumor sublines expressing either the classic or the
      atypical multidrug-resistance (MDR) phenotype to vinblastine or teniposide.
      Maximal non-cytotoxic concentrations of each modulator were tested and
      sensitization induces (SIs) were derived by comparing the drug concentration
      required to inhibit growth by 50% in their presence or absence. Like verapamil
      (10 microM) itself, three of the other modulators tested, namely, S9788 (4
      microM), flunarizine (20 microM) and quinidine (30 microM), resulted in 2- to 3
      fold sensitization of vinblastine against the parental CEM cells, and comparable
      effects were noted in the CEM/VM-1 cells, which were not cross-resistant to
      vinblastine. In contrast, cyclosporin A (0.5 microM) and B859-35 (2 microM) did
      not enhance vinblastine growth inhibition in these lines. However, the greatest
      sensitization with all the modulators was noted in the classic MDR VBL1000 cells,
      with SIs ranging from 40- to 350-fold, except for cyclosporin A, which proved
      ineffective at the concentration tested (SI, 2.6). The greatest extent of
      differential sensitization of these VBL1000 tumor cells occurred with quinidine
      or B859-35, which proved significantly more effective than verapamil alone.
      Combinations of modulators resulted in additive effects, with B859-35 plus
      cyclosporin A proving superior to B859-35 plus verapamil. In contrast, none of
      these compounds proved effective as a sensitizer to teniposide. The growth
      inhibitory effects of this drug were not modified significantly in either the 92
      fold teniposide-resistant VM-1 cells or in the parental cells. Addition of
      verapamil itself also failed to modulate teniposide growth inhibition in the
      VBL1000 cells, which express significant cross-resistance to this drug (36-fold).
      However, SI values of 3- to 5-fold were obtained using quinidine or B859-35.
      These results serve (a) to emphasise the need to monitor the effects of
      modulators not only on drug-resistant cells but also on their drug-sensitive
      counterparts so as to ensure differential sensitization such that normal
      sensitive tissues are not likely to be adversely influenced and (b) to highlight
      the observation that the extent of modulation differs depending not only on the
      antitumor drug used but also on the mechanism of drug resistance expressed. This
      in vitro model system appears to provide a useful screening system for resistance
      modulators and certainly could be used in attempts to identify alternative agents
      that may influence teniposide sensitivity in these drug-resistant sublines.

PMID- 8281627
TI  - Dose-dependent pharmacokinetics of rapamycin-28-N,N-dimethylglycinate in the
      mouse.
AB  - Rapamycin-28-N,N-dimethylglycinate methanesulfonate salt (RG), synthesized as a
      potential water-soluble prodrug to facilitate parenteral administration of the
      antineoplastic macrolide rapamycin (RA), is active against intracranially
      implanted human glioma in mice. Preclinical pharmacokinetic studies to evaluate
      the prodrug were conducted in male CD2F1 mice treated with 10, 25, 50 and 100
      mg/kg doses of RG by rapid i.v. injection. The plasma concentration of RG decayed
      in a distinctly triphasic manner following treatment with the 100 mg/kg dose;
      however, prodrug disposition was apparent biexponential at each of the lower
      doses. RG exhibited dose-dependent pharmacokinetics, characterized by an increase
      in the total plasma clearance from 12.5 to 39.3 ml.min-1.kg-1 for dosage
      escalations in the range 10-50 mg/kg, while clearance values at doses of 50 and
      100 mg/kg were similar. The terminal rate constants decreased linearly as the
      dose was increased from 10 to 100 mg/kg, eliciting an apparent prolongation of
      the biological half-life from 2.1 to 4.8 h. There was also a sequential increase
      in the steady state apparent volume of distribution from 1.73 to 8.75 l/kg. These
      observations are consistent with saturable binding of RG to plasma proteins while
      binding to tissue remains linear. Nevertheless, conversion to RA appeared to
      represent a prominent route of RG elimination. The molar plasma concentration of
      RA exceeded that of the prodrug within 30-90 min after i.v. treatment and
      declined very slowly thereafter, with plasma levels sustained between 0.1 and 10
      microM for 48 h at each of the doses evaluated. Thus, RG effectively served as a
      slow release delivery system for RA, implying the possibility of maintaining
      therapeutic plasma levels of the drug from a more convenient dosing regimen than
      a continuous infusion schedule. The present findings, coupled with the
      demonstrated in vivo activity of RG against human brain tumor models, warrant its
      continued development as a much needed chemotherapeutic agent for the treatment
      of brain neoplasms.

PMID- 8281628
TI  - GM-CSF, carboplatin, doxorubicin: a phase I study.
AB  - Dose intensification has the potential to increase the response frequency of
      chemosensitive tumors to chemotherapy. G-CSF and GM-CSF offer the possibility of
      dose-intensifying chemotherapy without prohibitive myelosuppression. A phase I
      study was undertaken to identify the maximum tolerated dose (MTD) of carboplatin
      that could be administered with a fixed dose of doxorubicin, 60 mg/m2,
      administered every 28 days. Further escalation of the carboplatin dose was then
      attempted, with the concomitant addition of GM-CSF 10 mg/kg per day on days 1-21.
      We had 21 patients, 13 with prior therapy, who were eligible. In all, 60 courses
      of therapy were delivered, all with doxorubicin and with carboplatin doses of 250
      mg/m2, 325 mg/m2 and 400 mg/m2. At carboplatin 400 mg/m2 and doxorubicin 60
      mg/m2, thrombocytopenia was dose limiting. The addition of GM-CSF did not allow
      further escalation. Of the 6 patients treated with carboplatin 400 mg/m2,
      doxorubicin 60 mg/m2, and GM-CSF, grade 4 granulocytopenia and thrombocytopenia
      were seen in 4 and 5 patients, respectively. The severity of thrombocytopenia was
      related to the calculated carboplatin AUC and also to baseline platelet count and
      prior therapy. In addition, the interaction of GM-CSF and chemotherapy,
      especially carboplatin-based, may be more complex than originally anticipated.

PMID- 8281630
TI  - High-dose VP16 cisplatinum in soft tissue sarcoma of children.
AB  - Nine children with soft tissue sarcomas, five of them rhabdomyosarcomas with
      initial metastatic disease, (one patient, partial response, one patient),
      refractory primary, (two patients, relapse, five patients) were treated with a
      combination of high-dose VP16 (100 mg/m2 daily for 5 days) and cisplatin (40
      mg/m2 daily for 5 days). The response rate was five out of nine or 55% (+/- 32%)
      (two complete and three partial, responses). Three of the five responders had
      rhabdomyosarcomas. The duration of response was 4-58 months (median 11 months).
      The toxicity was mainly hematological. Thus, the high-dose VP16-cisplatin
      association warrants further evaluation in soft tissue sarcoma in children.

PMID- 8281629
TI  - Pharmacokinetic and biotransformation studies of ormaplatin in conjunction with a
      phase I clinical trial.
AB  - Ormaplatin is a second-generation platinum (Pt) analogue with in vitro activity
      against some cisplatin-resistant malignant cell lines. We have evaluated the
      pharmacokinetics and biotransformations of ormaplatin during a phase I trial in
      which ormaplatin was administered by daily 30-min infusions on 5 consecutive days
      every 28 days. Sixteen patients received 25 courses at doses ranging from 5.0 to
      11.6 mg/m2 per day. Pharmacokinetic parameters determined for ultrafilterable Pt
      measured by atomic absorption spectrophotometry revealed a short half-life (t1/2
      16 min), moderate volume of distribution (Vd 12 l/m2), and relatively fast
      systemic clearance (Cls 544 ml/min per m2). Cls and percentage of drug unbound
      decreased during the 5-day administration period. Average systemic exposure
      increased with dose; however, inter-individual variability in Cls produced
      overlap in systemic exposure between the dose levels. The major active
      biotransformation product [PtCl2(dach)] was evaluated at the highest dose level
      by HPLC. This product decayed monoexponentially with a mean t1/2 of 13 min and a
      higher degree of pharmacokinetic variability than that of ultrafilterable Pt at
      this dose. No unreacted ormaplatin was detected; however, several inactive
      biotransformation products persisted for at least 120 min. Approximately 32% of
      the dose was excreted in the urine during the first day, one-third of this during
      the initial 1.5 h. The human pharmacokinetic characteristics of ormaplatin
      resemble those of cisplatin; however, additional study will be required to
      discern which analyte of ormaplatin correlates best with clinical effects.

PMID- 8281631
TI  - Images in Cardiovascular Medicine. Chloroquine-induced cardiomyopathy.

PMID- 8281632
TI  - Images in Cardiovascular Medicine. Multiloculated myxoid cyst of the popliteal
      artery.

PMID- 8281633
TI  - NHLBI research training and career development programs. "As ye sow ...".

PMID- 8281634
TI  - Low iron-binding capacity as a risk factor for myocardial infarction.
AB  - BACKGROUND: In a recent Finnish study, ferritin was suggested to be an
      independent risk factor for acute myocardial infarction. This study suggested
      that high levels of iron stores might thus be atherogenic and possibly explain
      partly the sex difference in the incidence of ischemic heart disease. METHODS AND
      RESULTS: A randomly selected group (n = 2036), men and women aged 25 to 74 years,
      were examined between June and September 1983. All classic risk factors for
      coronary artery disease were measured as well as basic hematologic parameters and
      the parameters of iron metabolism, ie, iron, total iron-binding capacity (TIBC),
      and ferritin. During the follow-up for 8.5 years, 81 subjects experienced acute
      myocardial infarction (63 men and 18 women). The differences in the iron
      parameters between men and women were almost exclusively seen in ferritin values
      (198 micrograms/L in men and 91 micrograms/L in women), whereas small differences
      were seen in TIBC. The Cox proportional hazards model was used to estimate the
      contribution of independent variables to the risk of myocardial infarction. TIBC
      was found to be a strong independent negative risk factor in men (RR = 0.95; 95%
      CI, 0.92 to 0.98), whereas ferritin (RR = 0.999; 95% CI, 0.997 to 1.001) or other
      iron parameters had no significant predictive power. Each increase in TIBC of 1
      mumol/L was associated with a 5.1% decrease in the risk of myocardial infarction.
      The classic major risk factors, ie, blood pressure, smoking, total cholesterol,
      and high-density lipoprotein, had significant independent correlation with
      myocardial infarction. When Cox multivariate analysis was carried out on both
      sexes combined, TIBC was still an independent negative risk factor, and the
      logarithmic transform of ferritin had a weak negative correlation but was not
      statistically significant. Sex was in this group still a very strong risk factor
      after taking into account all classic risk factors as well as the parameters of
      iron metabolism. CONCLUSIONS: This study suggests that transferrin, measured as
      TIBC, is an independent negative risk factor for myocardial infarction. Other
      parameters of iron metabolism, including ferritin, were not found to contribute
      to the risk.

PMID- 8281635
TI  - Heart disease deaths in a Japanese urban area evaluated by clinical and police
      records.
AB  - BACKGROUND: By national statistics, Japanese ischemic heart disease (IHD)
      mortality is one of the lowest of all industrialized countries, and the
      proportion of deaths due to heart failure in heart disease is the highest. There
      may be a difference in diagnostic preference between Japan and other
      industrialized countries. METHODS AND RESULTS: IHD deaths according to the death
      certificates were reevaluated with World Health Organization MONICA criteria for
      those 25 to 74 years old by use of clinical and police records in a Japanese city
      with a population of 347,000. Their cause of death was given on the death
      certificates as IHD (International Classification of Diseases [ICD], ninth
      revision, codes 410-414), heart failure (428), or other heart diseases (393-405,
      415-427, 429) in 1984 through 1986. Some deaths in 1985 through 1986 from stroke
      (430-438) or other diseases (250, 272, 278, 440-448, 797-799) were added. Of 409
      subjects, 397 (97%) could be examined. Reevaluation of the 106 deaths originally
      diagnosed as IHD yielded 73 IHDs and 11 sudden deaths of unknown origin (SD), and
      reevaluation of 160 deaths originally called heart failure yielded 26 IHDs and 50
      SDs. In total, reevaluation of all 397 deaths yielded 101 IHDs and 69 SDs. Some
      88% of SD cases were originally certified as heart failure (72%) or IHD (16%).
      Only two SDs were originally certified as stroke. CONCLUSIONS: Assuming that 30%
      of SDs were due to IHD, the number of IHD deaths would be 122, which is 11%
      larger than the number of IHD deaths according to the death certificates. After
      reevaluation, the IHD mortality in this study area still was the lowest in the
      industrialized countries.

PMID- 8281636
TI  - Pressure recovery in aortic valve stenosis.
AB  - BACKGROUND: Pressure recovery is the variable increase in lateral pressure
      downstream from a stenotic orifice. The magnitude and clinical significance of
      pressure recovery in aortic valve stenosis are poorly defined. METHODS AND
      RESULTS: We obtained high-fidelity pressure and velocity recordings in 11
      patients with isolated significant aortic valve stenosis at the time of
      diagnostic cardiac catheterization. Systematic catheter pullback from the left
      ventricular cavity revealed a consistent although variable subvalvular gradient.
      Further pullback across and distal to the region of the stenosed aortic valve
      revealed a consistent and progressive increase in the ascending aortic pressure.
      This increase in lateral pressure occurred pari passu with a diminution in
      amplitude of the velocity pulse. The extent of pressure recovery was directly
      related to systemic blood flow and transvalvular flow but inversely related to
      the Gorlin-derived aortic valve area. CONCLUSIONS: These findings have
      potentially important implications for the hemodynamic evaluation of mild to
      moderately severe aortic valve stenosis. The extent of pressure recovery may be
      of additional utility in the assessment of aortic valve stenosis under varying
      physiological states.

PMID- 8281637
TI  - Intramural myocardial shortening in hypertensive left ventricular hypertrophy
      with normal pump function.
AB  - BACKGROUND: In hypertensive left ventricular hypertrophy (LVH), intrinsic
      myocardial systolic function may be normal or depressed. Magnetic resonance
      tagging can depict intramural myocardial shortening in vivo. METHODS AND RESULTS:
      Tagged left ventricular magnetic resonance images were obtained in 30
      hypertensive subjects with LVH (mean LV mass index, 142 +/- 41 g/m) and normal
      ejection fraction (mean, 64 +/- 9%) using spatial modulation of magnetization. In
      26 subjects, circumferential myocardial shortening (%S) was compared with results
      obtained in 10 normal subjects at endocardium, midwall, and epicardium on up to 4
      short-axis slices each. Similarly, in 10 subjects, midwall long-axis shortening
      at basal, midventricular, and apical sites was compared with results obtained in
      12 normal volunteers. Circumferential %S was reduced in hypertensive subjects.
      Mean shortening was 29 +/- 6% at the endocardium in hypertensive subjects versus
      44 +/- 6% in normal subjects (P = .0001); 20 +/- 6% at the midwall versus 30 +/-
      6% (P = .0001); and 13 +/- 5% at the epicardium versus 21 +/- 5% (P = .0002).
      However, the transmural gradient in percent shortening from endocardium to
      epicardium in hypertensive subjects paralleled that in normal subjects. The
      normal base-to-apex gradient in circumferential %S was absent in LVH. In contrast
      to normal subjects, circumferential %S showed regional heterogeneity in
      hypertensive subjects, being maximal in the lateral wall and least in the
      inferior wall. Longitudinal shortening was also uniformly depressed in
      hypertensive subjects: 10 +/- 9% at the base versus 21 +/- 6% in normal subjects
      (P = .0001); 14 +/- 8% at the midventricle versus 18 +/- 3% (P = .03); and 14 +/-
      8% at the apex versus 18 +/- 4% (P = .04). CONCLUSIONS: In hypertensive LVH with
      normal pump function, intramural circumferential and longitudinal myocardial
      shortening are depressed.

PMID- 8281638
TI  - Liposome-mediated gene transfer into human vascular smooth muscle cells.
AB  - BACKGROUND: Complexing recombinant DNA with cationic liposomes is a convenient
      means of introducing foreign genes into cells (lipofection) and could potentially
      form the basis for genetically modifying diseased blood vessels in patients. The
      mechanism of lipofection is incompletely understood, but it is recognized that
      the degree of successful gene transfer is highly dependent on cell type. To date,
      there has been no reported experience with lipofection of human vascular smooth
      muscle cells. METHODS AND RESULTS: Primary cultures of human vascular smooth
      muscle cells were transfected under optimized conditions with a plasmid
      expressing either firefly luciferase (Luc) or nuclear-localized beta
      galactosidase (NL-beta-gal). Cells were derived from either normal human internal
      mammary arteries (n = 6), fragments of primary atherosclerotic plaque (n = 4), or
      fragments of restenotic lesions (n = 5). Concurrent lipofection of rabbit
      vascular smooth muscle cells and NIH 3T3 cells was performed as well. Cultures
      derived from 15 patients all demonstrated positive expression of the reporter
      gene. Compared with NIH 3T3 cells, however, expression in human vascular smooth
      muscle cells was markedly reduced: in cells derived from internal mammary artery,
      Luc expression, normalized for protein content, was 123-fold lower than in NIH
      3T3 cells, whereas the proportion of cells expressing NL-beta-gal was 30-fold
      lower. Luc expression in cells derived from restenotic tissue was significantly
      greater than from cells derived from primary plaque (P < .03). Within a given
      population of cells, the mitotic index of cells expressing the recombinant gene
      was significantly higher than the mitotic index for the total population of cells
      (P < .05). Finally, cotransfection experiments, in which lipofection of smooth
      muscle cells was performed using genes for NL-beta-gal and for human growth
      hormone, showed that among positive transfects, a high proportion of cells (23%
      to 36%) coexpressed both genes. CONCLUSIONS: The efficiency of successful
      lipofection in human vascular smooth muscle cells in vitro is low. Transfection
      appears to be preferentially facilitated in cells derived from restenotic tissue,
      and specific properties of smooth muscle cells, including growth rates, appear to
      be critical for successful transfection. Further elucidation of cell properties
      that promote transfection is required to augment the efficiency of liposome
      mediated gene transfer in human vascular cells.

PMID- 8281639
TI  - Mitral valve replacement versus mitral valve repair. A Doppler and quantitative
      stress echocardiographic study.
AB  - BACKGROUND: Standard mitral valve replacement (MVR) in patients with chronic
      mitral regurgitation results in consistent reductions in resting postoperative
      ejection fraction. This has been attributed to removal of the low-impedance
      ejection pathway into the left atrium or to disruption of the chordal apparatus.
      Mitral valve repair (MVP) does not reduce ejection fraction at rest. However,
      whether MVP confers any advantages with regard to dynamic left ventricular
      performance has not been investigated. The aim of this study was to directly
      compare standard MVR with MVP and to determine their respective influences on
      ventricular ejection performance during bicycle exercise. METHODS AND RESULTS:
      Ten consecutive patients with pure chronic mitral regurgitation who underwent MVP
      and 10 patients matched for age, sex, and preoperative ejection fraction who
      underwent standard MVR for pure chronic mitral regurgitation performed symptom
      limited, graded upright bicycle exercise with simultaneous Doppler and
      quantitative two-dimensional echocardiography. Patients with MVP had
      significantly greater rest (55 +/- 12%) and exercise (63 +/- 11%) ejection
      fractions than matched patients with MVR (40 +/- 13% [P < .0001] and 42 +/- 17%
      [P < .005], respectively). End-systolic circumferential wall stress was
      significantly lower at rest (190 +/- 36 versus 244 +/- 46; P < .03) and at peak
      exercise (231 +/- 46 versus 300 +/- 52; P < .02) in patients with MVP. At peak
      exercise, left ventricular shape was significantly more spherical in patients
      with MVR than those with MVP (1.84 +/- 0.31 versus 2.45 +/- 0.59; P < .02).
      CONCLUSIONS: MVR with chordal transection resulted in significant reductions in
      rest and exercise ejection fraction. This was caused in part by a significant
      increase in end-systolic circumferential wall stress. MVP resulted in improved
      rest and exercise ejection indexes, primarily due to a marked reduction in end
      systolic stress and maintenance of a more ellipsoidal chamber geometry.

PMID- 8281640
TI  - Rheumatic fever and the HLA complex. A cosegregation study.
AB  - BACKGROUND: Considering the controversial results published in the literature
      concerning associations between human leukocyte antigens (HLA) and rheumatic
      fever (RF), the purpose of the present study was to investigate by means of
      cosegregation analysis the participation of HLA genes in susceptibility to RF.
      METHODS AND RESULTS: The sample reported here was composed of 51 affected and 66
      healthy individuals belonging to 22 genetically informative families. The
      comparison (chi 2 goodness-of-fit test) of the observed numbers of identical-by
      descent (IBD) HLA haplotypes among all affected individuals (siblings, cousins,
      and uncle/nephew and grandparent/grandchild type of pairs) with the expected ones
      under the assumption of independent segregation of HLA alleles and the
      presumptive RF susceptibility gene gave a value of P = .088. Since the number of
      subjects studied was relatively small and the rejection level obtained was near
      the usual .05 significance level, we calculated the expected HLA IBD scores in
      the 13 pairs of affected sibs of our sample for all possible frequencies of the
      presumptive RF susceptibility gene. This analysis allowed clear rejection of a
      recessive mode, considering susceptibility gene frequencies lower than 20%,
      whereas the observed values fitted very well a dominant mode of inheritance, with
      penetrance (K) values varying between 0.5 and 0.9 and a frequency of the
      susceptibility gene of at least 1%. CONCLUSIONS: The present data support the
      hypothesis of an RF susceptibility gene within or very near the HLA complex.

PMID- 8281641
TI  - Alterations in left ventricular twist mechanics with inotropic stimulation and
      volume loading in human subjects.
AB  - BACKGROUND: Left ventricular (LV) twist, the longitudinal gradient of
      circumferential rotation about the LV long axis, may play an important role in
      the storage of potential energy at end systole and its subsequent release as
      elastic recoil during early diastole; however, the effects of load and inotropic
      state on LV systolic twist and diastolic untwist in human subjects have not
      previously been characterized. METHODS AND RESULTS: Six cardiac transplant
      recipients with 12 implanted radiopaque midwall LV myocardial markers were
      studied 1 year after transplantation. Biplane cinefluoroscopic marker images and
      LV pressure were recorded during control conditions and after afterload
      augmentation (methoxamine, 5 to 10 micrograms.kg-1 x min-1), inotropic
      stimulation (dobutamine, 5 micrograms.kg-1 x min-1), and preload augmentation
      (volume loading with normal saline). Systolic twist dynamics were assessed by
      maximum twist (Tmax[rad/cm]), peak negative twist rate (-dT/dtmin[rad.cm-1 x s
      1]), and the slope of the twist normalized-ejection fraction relation (T-nEFR,
      Msys[rad/cm]) during systole. Diastolic untwist was assessed by the peak positive
      untwist rate (+dT/dtmax [rad.cm-1 x s-1]) and the slopes (rad/cm) of the T-nEFR
      during early diastole (Mear-dia) and mid diastole (Mmid-dia). Compared with
      control values, LV pressure and volume loading had no significant effect on Tmax,
      -dT/dtmin, or Msys; however, inotropic stimulation significantly increased all
      parameters describing systolic twist (Tmax: -0.10 +/- 0.03 versus -0.06 +/- 0.02
      rad/cm, P < .001; -dT/dtmin: -0.72 +/- 0.19 versus -0.44 +/- 0.22 rad.cm-1 x s-1,
      P < .001; Msys: -0.10 +/- 0.03 versus -0.06 +/- 0.01 rad/cm, P < .001). Pressure
      loading had no effect on early diastolic untwisting; however, dobutamine
      significantly increased M(ear)-dia (-0.24 +/- 0.06 versus -0.13 +/- 0.04 rad/cm,
      P < .0001) and +dT/dtmax (0.78 +/- 0.24 versus 0.45 +/- 0.16 rad.cm-1 x s-1, P <
      .001). Conversely, volume loading significantly decreased M(ear)-dia (-0.08 +/-
      0.04 versus -0.13 +/- 0.04 rad/cm, P < .05). M(ear)-dia correlated directly with
      LV contractile state (as assessed as maximum dP/dt, r = .60, P < .0001) and
      inversely with end-systolic volume (r = -.87, P < .0001) but was unrelated to
      stroke volume (r = .08, P = .30) or LV afterload (estimated as effective arterial
      elastance, r = .08, P = .29). Mmid-dia did not change during any intervention.
      CONCLUSIONS: In conscious human transplant patients, (1) pressure and volume
      loading do not affect systolic LV twist; (2) dobutamine augments systolic twist
      and early diastolic untwisting, suggesting more end-systolic potential energy
      storage and early diastolic elastic recoil with enhanced inotropic state; (3)
      volume loading decreases early diastolic untwisting, possibly reflecting
      diminished recoil forces after preload augmentation associated with larger end
      systolic volumes (ESV); and (4) M(ear)-dia correlates strongly with ESV (in an
      inverse fashion), and less strongly, but directly, with LV dP/dtmax.

PMID- 8281642
TI  - Structural basis of end-stage failure in ischemic cardiomyopathy in humans.
AB  - BACKGROUND: Ischemic cardiomyopathy is characterized by myocyte loss, reactive
      cellular hypertrophy, and ventricular scarring. However, the relative
      contribution of these tissue and cellular processes to late failure remains to be
      determined. METHODS AND RESULTS: Ten hearts were obtained from individuals
      undergoing cardiac transplantation as a result of chronic coronary artery disease
      in its terminal stage. An identical number of control hearts were collected at
      autopsy from patients who died from causes other than cardiovascular disease, and
      morphometric methodologies were applied to the analysis of the left and right
      ventricular myocardium. Left ventricular hypertrophy evaluated as a change in
      organ weight, aggregate myocyte mass, and myocyte cell volume per nucleus showed
      increases of 85%, 47%, and 103%, respectively. Corresponding increases in the
      right ventricle were 75%, 74%, and 112%. Myocyte loss, which accounted for 28%
      and 30% in the left and right ventricles, was responsible for the difference in
      the assessment of myocyte hypertrophy at the ventricular, tissue, and cellular
      levels. Left ventricular muscle cell hypertrophy was accomplished through a 16%
      and 51% increase in myocyte diameter and length, whereas right ventricular
      myocyte hypertrophy was the consequence of a 13% and 67% increase in these linear
      dimensions, respectively. Moreover, a 36% reduction in the number of myocytes
      included in the thickness of the left ventricular wall was found. Collagen
      accumulation in the form of segmental, replacement, and interstitial fibrosis
      comprised an average 28% and 13% of the left and right ventricular myocardia,
      respectively. The combination of cell loss and myocardial fibrosis, myocyte
      lengthening, and mural slippage of cells resulted in 4.6-fold expansion of left
      ventricular cavitary volume and a 56% reduction in the ventricular mass-to
      chamber volume ratio. CONCLUSIONS: These results are consistent with the
      contention that both myocyte and collagen compartments participate in the
      development of decompensated eccentric ventricular hypertrophy in the
      cardiomyopathic heart of ischemic origin.

PMID- 8281643
TI  - Effects of intracoronary acetylcholine and atropine on basal and dobutamine
      stimulated left ventricular contractility.
AB  - BACKGROUND: The role of cholinergic pathways in modulating left ventricular
      contractile function in humans is not known. This study evaluated the effect of a
      cholinergic agonist (acetylcholine) and antagonist (atropine) on basal and beta
      adrenergically stimulated left ventricular contractile function in normal
      subjects and subjects with denervated hearts after cardiac transplantation.
      METHODS AND RESULTS: Six subjects with normal left ventricular function and seven
      subjects who were 1 to 3 years after cardiac transplantation were studied.
      Acetylcholine, atropine, and the beta-adrenergic agonist dobutamine were infused
      via the left main coronary artery, and changes in left ventricular contractile
      function were assessed by measurement of peak +dP/dt. Intracoronary dobutamine
      increased +dP/dt by 70 +/- 15% and 66 +/- 20% in the normal subjects and
      transplant recipients, respectively. Intracoronary acetylcholine and atropine
      alone each had no effect on left ventricular +dP/dt in either normal subjects or
      transplant recipients. The concurrent infusion of acetylcholine with dobutamine
      reduced the response to dobutamine by 66 +/- 10% and 79 +/- 9% in normal subjects
      and transplant recipients, respectively. The concurrent infusion of atropine with
      dobutamine potentiated the response to dobutamine by 25 +/- 7% in normal subjects
      but had no effect in transplant recipients. CONCLUSIONS: Stimulation and
      inhibition of cholinergic receptors in the human heart can modulate the positive
      inotropic response to beta-adrenergic stimulation.

PMID- 8281644
TI  - Blood pressure modulation by central venous pressure and respiration. Buffering
      effects of the heart rate reflexes.
AB  - BACKGROUND: Despite constant fluctuations in cardiac preload caused by the
      effects of respiration and changes in posture on venous return to the heart,
      arterial blood pressure remains remarkably constant. The effects of instantaneous
      lung volume (ILV) and variations of central venous pressure (CVP) on blood
      pressure (BP) were studied by use of frequency domain techniques to quantify the
      contribution of heart rate (HR) reflexes to attenuation of the effects of changes
      in right ventricular preload on arterial pressure. METHODS AND RESULTS: Random
      independent variation of ILV, then CVP (obtained using lower-body negative
      pressure), was performed in eight humans in the supine position. HR, ILV, CVP,
      and systolic (SBP) and diastolic (DBP) BPs were recorded during control periods
      and after complete blockade obtained by use of 0.04 mg/kg atropine and 0.2 mg/kg
      propranolol. A frequency-domain analysis was performed on pairwise relations by
      the cross-spectral technique. During autonomic blockade, fluctuations in CVP were
      induced up to 0.14 Hz but caused corresponding changes in arterial pressure only
      up to 0.08 Hz (P < .02), indicating a mechanical damping effect of the heart and
      pulmonary vasculature. Fluctuations of BP were also delayed from CVP by 1.55 to
      2.10 seconds. At frequencies < 0.1 Hz, relations of CVP to all indices of BP
      increased with blockade (CVP-SBP, 0.9 +/- 0.5 versus 2.7 +/- 0.8 mm Hg/mm Hg, P <
      .01; CVP-DBP, 1.3 +/- 0.4 versus 4.3 +/- 1.4 mm Hg/mm Hg, P < .01; CVP-pulse
      pressure [PP], 1.0 +/- 0.3 versus 1.9 +/- 0.8 mm Hg/mm Hg, P < .05). Higher
      frequency fluctuations of arterial BP were a relatively pure manifestation of
      respiratory activity. At frequencies from 0.15 to 0.35 Hz, the relation of ILV to
      SBP was unchanged with blockade, whereas relations of ILV to DBP and PP decreased
      (ILV-DBP, 6.1 +/- 3.5 versus 3.3 +/- 2.2 mm Hg/L, P < .02; ILV-PP, 7.0 +/- 4.3
      versus 2.7 +/- 2.2 mm Hg/L, P < .01). An associated change in phase of these
      relations suggested that neurally mediated changes in HR may offset mechanical
      effects caused by respiration. CONCLUSIONS: Both slow changes of BP (< 0.08 Hz)
      induced by variations of CVP and more rapid changes induced by ILV are actively
      buffered by heart rate reflexes. During blockade, the mechanical properties of
      interposed cardiopulmonary structures limit CVP-induced fluctuations of BP. These
      findings have implications for BP regulation in pathological conditions
      associated with impairment of HR control.

PMID- 8281645
TI  - Assessment of the immediate effects of cardiopulmonary bypass on left ventricular
      performance by on-line pressure-area relations.
AB  - BACKGROUND: Pressure-volume relations have been established as useful measures of
      left ventricular (LV) performance. Application of these methods to the
      intraoperative setting have been limited because of difficulties acquiring LV
      volume data. Transesophageal echocardiographic automated border detection can
      measure LV cross-sectional area as an index of volume, which can be coupled with
      pressure data to construct pressure-area loops on-line. The purpose of this study
      was to evaluate intraoperative LV performance in patients undergoing coronary
      bypass surgery before and immediately after cardiopulmonary bypass using on-line
      pressure-area relations. METHODS AND RESULTS: Studies were attempted in 13
      consecutive patients. Simultaneous measures of LV cross-sectional area, LV
      pressure, and electromagnetic flow probe-derived aortic flow recorded on a
      computer work station interfaced with the ultrasound system. Pressure-area loops
      were compared with simultaneous pressure-volume loops constructed from pressure
      and flow data during inferior vena caval occlusions before and after bypass.
      Pressure-volume calculations (end-systolic elastance, maximal elastance, and
      preload-recruitable stroke work) were then applied to pressure-area loops with
      area substituted for volume data. Changes in stroke force from pressure-area
      loops were closely correlated with changes in estimates of stroke work from
      pressure-volume loops for individual patients before bypass (r = .99 +/- .03, SEE
      = 5 +/- 2%, n = 10) and after bypass (r = .96 +/- .05, SEE = 5 +/- 2%, n = 9).
      Pressure-area estimates of end-systolic elastance, maximal elastance, and preload
      recruitable stroke force decreased significantly from before to after
      cardiopulmonary bypass in the 7 patients with paired data sets. Load-dependent
      measures of LV function (stroke volume, cardiac output, and fractional area
      change) were unchanged after surgery in these same patients. CONCLUSIONS:
      Intraoperative pressure-area loops may be acquired and displayed on-line using
      transesophageal echocardiographic automated border detection and readily analyzed
      in a manner similar to pressure-volume loops. LV performance was depressed
      immediately after cardiopulmonary bypass compared with before. On-line pressure
      area relations may be clinically useful to assess LV performance in patients
      undergoing cardiac surgery in whom load and contractility may be expected to vary
      rapidly.

PMID- 8281646
TI  - Prediction of outcome after valve replacement for rheumatic mitral regurgitation
      in the era of chordal preservation.
AB  - BACKGROUND: Noninvasive predictors of important outcomes after valve replacement
      for mitral regurgitation have not been examined in a rheumatic population (in
      whom the results of valve repair are suboptimal) in the era of chordal
      preservation. Timing of valve replacement thus remains a difficult question in
      rheumatic mitral regurgitation. METHODS AND RESULTS: Of 278 patients followed
      after valve replacement, 66 had pure or predominant mitral regurgitation, and in
      61 of these the etiology was rheumatic. The mean age was 24 years. After a mean
      follow-up of 24 +/- 10 months, the ability of preoperative clinical and
      echocardiographic data to predict outcome was assessed prospectively, and the
      possible impact of chordal preservation (n = 35) on survival and post-operative
      left ventricular function was examined retrospectively. There were no
      perioperative deaths. There were six postoperative deaths, all the result of
      heart failure and all related to left ventricular dysfunction. The mean
      probability of survival was .90 at 16 months. In a stepwise Cox proportional
      hazards regression analysis, the only independent predictor of postoperative
      death was preoperative end-systolic diameter. According to a logistic model, the
      probabilities of death (n = 6) and death or severe heart failure (n = 7)
      increased abruptly at a preoperative end-systolic diameter of 51 mm
      (probabilities, .23 and .31, respectively), and the accuracy of this cut point
      for predicting outcomes was 97% and 98%, respectively. Multiple linear regression
      analysis identified a large preoperative end-systolic diameter and the need to
      use tricuspid annuloplasty as significant independent predictors of postoperative
      fractional shortening; the use of chordal preservation (n = 35) was not a
      predictor of postoperative fractional shortening. A good outcome was predicted at
      a preoperative end-systolic diameter of 40 mm: probability of death or heart
      failure was .0001, and predicted mean postoperative fractional shortening was
      0.27 after mitral valve replacement without tricuspid annuloplasty. CONCLUSIONS:
      When preoperative end-systolic diameter is more than 50 mm, a poor postoperative
      outcome is predicted despite chordal preservation in relatively young patients
      with rheumatic mitral regurgitation, and alternative strategies should therefore
      be considered. When preoperative end-systolic diameter is 40 mm or less, an
      excellent outcome is predicted, and close observation without surgery would
      appear to be reasonable in the absence of symptoms.

PMID- 8281647
TI  - Enhanced left ventricular performance in endurance trained older men.
AB  - BACKGROUND: The age-associated decline in aerobic exercise capacity is partially
      reversible by endurance exercise training. Moderate-intensity endurance exercise
      training increases aerobic exercise capacity mediated, in part, by improvement of
      stroke volume and left ventricular performance in older men. The present study
      was designed to characterize the nature of cardiovascular adaptations to
      strenuous endurance exercise of long duration and to delineate the mechanisms
      underlying increased stroke volume and cardiac output in highly trained older
      endurance athletes. METHODS AND RESULTS: Nine male master athletes (MA: 64 +/- 2
      years old, mean +/- SEM) and 9 older sedentary healthy men (controls: 63 +/- 1
      year) were studied. Left ventricular systolic function was evaluated with the use
      of cardiac blood pool imaging and echocardiography. Maximal O2 uptake (VO2max)
      was 50.4 +/- 1.7 mL.kg-1 x min-1 in the MA and 29.6 +/- 1.4 mL.kg-1 x min-1 (P =
      .0001) in controls. Systolic and mean blood pressures at rest and during exercise
      were not different in the two groups. Left ventricular systolic function at peak
      exercise was higher in the MA than in sedentary controls as evidenced by (1) a
      higher left ventricular functional reserve (delta EF: 12.4 +/- 2 versus 5.6 +/-
      2.5, P = .05), (2) a large decrease in end-systolic volume during exercise (MA:
      56 +/- 4 mL at rest and 42 +/- 5 mL at peak exercise, P = .007; controls: 43 +/-
      2 mL at rest and 42 +/- 6 mL at peak exercise, P = .35) with no differences in
      systolic blood pressure, (3) a higher left ventricular fractional shortening at
      peak exercise (MA: 52 +/- 2.6%; controls: 45 +/- 1%, P = .046) at comparable
      values for end-systolic wall stress (MA: 56 +/- 12 g/cm2; controls: 53 +/- 7
      g/cm2, P = .50), and (4) a greater decrease in end-systolic diameter at peak
      exercise in the MA than in controls (MA: -1.2 +/- 0.16 cm versus -0.57 +/- 0.13
      cm, P = .014) despite no significant differences between the changes in end
      systolic wall stress during exercise (MA: -15.5 +/- 7.5 g/cm2, controls: -11.0 +/
      9.0 g/cm2, P = .6). MA had a larger end-diastolic volume at rest (153 +/- 6
      versus 132 +/- 4 mL, P = .009) with a normal wall thickness-to-radius ratio (0.34
      +/- 0.02). Peak exercise stroke volume was higher (P = .023) in the MA (132 +/- 6
      mL/min) than in the sedentary controls (111 +/- 6 mL/min). Changes in stroke
      volume correlated strongly with changes in ejection fraction in the MA (r = .80,
      P = .010) but not in sedentary controls (r = .59, P = .097). Further, changes in
      stroke volume from rest to exercise correlated strongly with changes in end
      diastolic volume in both MA (r = .78, P = .013) and sedentary controls (r = .73,
      P = .026), suggestive of reliance of stroke volume on end-diastolic volume and
      preload. However, for a given increase in end-diastolic volume, the rise in
      stroke volume during exercise was significantly larger in the MA than in
      controls, which, in the absence of differences in mean blood pressures, indicates
      that enhanced left ventricular systolic function independent of preload plays an
      additional role in maintaining a higher stroke volume at peak exercise in the
      highly trained older men. CONCLUSIONS: Cardiac adaptations in older endurance
      trained men are characterized by volume-overload left ventricular hypertrophy and
      enhancement of left ventricular systolic performance at peak exercise. These
      adaptive responses contribute to enhanced stroke volume at peak exercise in older
      endurance trained men.

PMID- 8281648
TI  - Short-coupled variant of torsade de pointes. A new electrocardiographic entity in
      the spectrum of idiopathic ventricular tachyarrhythmias.
AB  - BACKGROUND: Torsade de pointes is characterized not only by its particular ECG
      pattern but by its context of congenital or acquired long QT syndrome and the
      long coupling interval of the initial premature beat. METHODS AND RESULTS: We
      observed 14 patients aged 34.6 +/- 10 years (mean +/- SD) with no structural
      heart disease who presented with syncope related to a typical ECG aspect of
      torsade de pointes. However, there was no evidence of long QT syndrome, and the
      torsade had the unusual particularity of an extremely short coupling interval of
      the first beat or of the isolated premature beats (245 +/- 28 milliseconds). In
      10 cases they deteriorated into ventricular fibrillation. Four patients had a
      familial history of sudden death. Only 2 patients had a tachyarrhythmia inducible
      by programmed stimulation. At Holter recordings the heart rate variability was
      globally and significantly depressed, the vagal limb of the autonomic nervous
      system being predominantly affected. During a mean follow-up of 7 years there
      were 5 deaths (4 sudden). Nine patients are alive, 3 with implanted
      defibrillators and 6 treated with verapamil alone. Unlike the other types of
      antiarrhythmic agents including beta-blockers and amiodarone, verapamil is in our
      experience the only drug apparently active on the arrhythmias; however, it does
      not prevent sudden death. CONCLUSIONS: The short-coupled variant of torsade de
      pointes should be identified because of their ECG pattern and the risk of sudden
      death in young adults with no structural heart disease.

PMID- 8281649
TI  - Rise in chronic defibrillation thresholds in nonthoracotomy implantable
      defibrillator.
AB  - BACKGROUND: To establish the chronic stability of defibrillation thresholds
      (DFTs) in a transvenous cardioverter/defibrillator (TCD) system, we studied 37
      consecutive patients with TCD systems implanted for > 6 months. METHODS AND
      RESULTS: DFT was measured by a step-down method at implant and 2 and 6 months
      later. The mean ejection fraction was 34.5 +/- 14.3%. Coronary artery disease
      with previous myocardial infarction was present in 31 patients. The mean DFT rose
      from 13.3 +/- 4.3 J at implant to 16.5 +/- 4.7 J at 2 months (P < .001) and 17.6
      +/- 5.4 J at 6 months (P < .0001). ANOVA revealed a statistically significant
      rise in DFT over time (P < .0005). At 2 months, 25 patients had a rise in DFT,
      and 14 had a rise > or = 5 J. The observed rise at 2 months persisted in 19
      patients. A chronic rise, defined as > or = 5 J rise at 6 months, occurred in 17
      patients. Univariate analysis of clinical as well as implant variables revealed
      no predictors of a rise in DFT in this group. CONCLUSIONS: We conclude that there
      is a significant rise in DFT at 2 and 6 months in this TCD system. Although the
      chronic threshold remained well within the available energy range of the pulse
      generator, this observation has important implications for implantation
      guidelines, programming, and future pulse generator development for TCD patients.

PMID- 8281650
TI  - Genotype-phenotype correlations in hypertrophic cardiomyopathy. Insights provided
      by comparisons of kindreds with distinct and identical beta-myosin heavy chain
      gene mutations.
AB  - BACKGROUND: We have previously described two distinct mutations in the beta
      myosin heavy chain gene with markedly different clinical presentations and
      outcome: The 908Leu-->Val mutation was associated with a low disease penetrance
      and a benign prognosis. In contrast, the 403Arg-->Gln mutation in a Caucasian
      kindred was associated with a 100% disease penetrance and high incidence of
      sudden cardiac death. Recently, another mutation, 606Val-->Met, has been reported
      to be associated with "near normal survival" and offered as evidence for the
      benign nature of neutral charge substitutions. METHODS AND RESULTS: We report (1)
      a large kindred (245 family members at risk of inheriting the disease gene) with
      a 256Gly-->Glu mutation characterized by a similar disease penetrance in adults
      and in children (56% and 60%, respectively) and a cumulative sudden cardiac death
      rate of only 2% at 50 years of age, (2) a kindred with the 606Val-->Met mutation
      with four sudden cardiac deaths in eight affected individuals, and (3) a Korean
      kindred with the 403Arg-->Gln mutation. Although the disease occurred early and
      was associated with a high prevalence of myocardial ischemia in both of our
      kindreds with the 403Arg-->Gln mutation, no sudden cardiac death or syncope has
      occurred in the Korean kindred. Furthermore, in the Caucasian kindred, all
      patients had nonobstructive hypertrophic cardiomyopathy, but most of the patients
      in the Korean kindred had left ventricular outflow obstruction. CONCLUSIONS: The
      conclusions are as follows: (1) Although several sudden cardiac deaths are
      sufficient to establish that a mutation is malignant, study of a large kindred is
      necessary to be certain that a mutation is benign. To date, only the 908Leu-->Val
      and the 256Gly-->Glu mutations satisfy this requirement. (2) The 256Gly-->Glu
      mutation demonstrates that not all mutations that result in a charge change are
      malignant. (3) Conversely, the 606Val-->Met mutation is malignant in some
      kindreds; hence, despite the absence of a charge change, minor substitutions in
      critical regions of beta-myosin heavy chain protein may also have serious
      consequences. (4) The diverse ethnic origins of the two 403Arg-->Gln kindreds
      provide evidence suggesting that the identical mutation occurred independently
      and was associated with different genetic backgrounds. Their distinct phenotypes
      underline the importance of modifying genes and nongenetic factors.

PMID- 8281651
TI  - Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial
      fibrillation and paroxysmal supraventricular tachycardia.
AB  - BACKGROUND: Paroxysmal atrial fibrillation and paroxysmal supraventricular
      tachycardia are recognized clinically when patients seek treatment for symptoms
      due to recurrent arrhythmias; atrial fibrillation also increases the risk of
      stroke. The frequency with which asymptomatic arrhythmias occur in patients with
      these arrhythmias is unknown. METHODS AND RESULTS: Twenty-two patients with
      paroxysmal atrial fibrillation (n = 8) or paroxysmal supraventricular tachycardia
      (n = 14) were studied for 29 days with two different ambulatory ECG-monitoring
      techniques to measure the relative frequency of asymptomatic and symptomatic
      arrhythmias. All class I antiarrhythmic drugs, calcium channel blockers, beta
      blockers, and digitalis were withheld. Sustained asymptomatic arrhythmia events
      (defined as lasting at least 30 seconds) were documented using continuous
      ambulatory ECG monitoring once weekly for a total of 5 of the 29 study days;
      symptomatic arrhythmia events were documented using transtelephonic ECG
      monitoring for all 29 days of the study. In the group of patients with paroxysmal
      atrial fibrillation, asymptomatic arrhythmia events occurred significantly more
      frequently than symptomatic arrhythmia events; the mean rates, expressed as
      events/100 d/patient (95% confidence interval), were 62.5 (40.4, 87.3) and 5.2
      (2.7, 9.0) (P < .01); the ratio of the mean rates was 12.1 (5.8, 26.4). In
      contrast, in the group of patients with paroxysmal supraventricular tachycardia,
      asymptomatic arrhythmia events were significantly less frequent than symptomatic
      arrhythmia events; the mean rates were 0.0 (0.0, 5.3) and 7.4 (5.0, 10.6) (P =
      .02). The ratio of the mean rates was 0.0 (0.0, 0.8). CONCLUSIONS: In a group of
      patients with paroxysmal atrial fibrillation, sustained asymptomatic atrial
      fibrillation occurs far more frequently than symptomatic atrial fibrillation.
      However, it is not known whether asymptomatic atrial fibrillation is a potential
      risk factor for stroke even when patients are not having symptomatic arrhythmias.

PMID- 8281652
TI  - "Intramural" residual interventricular defects after repair of conotruncal
      malformations.
AB  - BACKGROUND: We report an unusual type of residual interventricular communication
      in patients with conotruncal malformations in which the aorta is completely or
      partly aligned with the right ventricle (RV). Interventricular communications
      after surgical repair usually result from additional defects, patch dehiscence,
      or incomplete closure and lie in the septal plane. However, after a right
      ventricular aorta is baffled to the left ventricle, the ventricular septal defect
      (VSD) patch and RV free wall form part of the systemic outflow tract. This "neo
      left ventricular" outflow tract may provide a location for residual
      interventricular communications out of the septal plane. METHODS AND RESULTS: We
      reviewed echocardiographic, angiographic, and clinical records of patients who
      had one or more residual interventricular communications out of the plane of the
      ventricular septum after repair of a conotruncal anomaly. Between June 1990 and
      October 1992, we observed such defects in eight patients, 5 to 26 years old,
      after repair of double-outlet right ventricle (n = 6), tetralogy of Fallot (n =
      1), or truncus arteriosus (n = 1). In each, the VSD patch was anchored to the RV
      free wall near the aortic root. Nonetheless, channels were observed around the
      edge of the patch, between the neo-systemic outflow tract and the right
      ventricle. All patients had right ventricular hypertension; in seven, the
      pulmonary-to-systemic flow ratio (Qp:Qs) was > or = 2. At multiple unsuccessful
      reoperations (two to four per patient), the patch edges appeared securely
      attached to myocardium. Angiographic views profiling the septum failed to
      localize these defects, since they are not in the native septum.
      Echocardiographic detection of such anterior defects can be difficult.
      Transcatheter umbrella closure was attempted in the seven patients with large
      shunts; success was limited by the multiplicity of flow channels. Umbrella
      closure eliminated the need for further reoperation in four of seven patients,
      one patient died suddenly awaiting reoperation, and two deaths followed
      reoperation. CONCLUSIONS: "Intramural" residual interventricular defects are
      difficult to diagnose by all modalities. Umbrella placement may reduce the left
      to-right shunt. Successful surgical closure may require removal and reattachment
      of the anterior portion of the patch.

PMID- 8281653
TI  - Pulmonary atresia with ventricular septal defect in adults.
AB  - BACKGROUND: Multistage surgery culminating in completed hemodynamic repair is now
      performed for pulmonary atresia with ventricular septal defect (PA-VSD).
      Justification for operation in patients with an adequate collateral pulmonary
      circulation is controversial. Data on natural adult survival are scant but are
      necessary to provide the rationale for multistage reconstructive procedures.
      METHODS AND RESULTS: All cyanotic adults with PA-VSD in the UCLA Adult Congenital
      Heart Disease Center Registry from 1978 through 1992 formed the basis for this
      study. Registry data and echocardiographic, hemodynamic, and angiographic
      information were used to determine longevity, clinical course, and operative
      feasibility. Of 26 patients, 16 were unoperated when referred (group A), and 10
      had been palliated before age 18 years (group B). Two thirds were 18 to 29 years
      old. Only 2 patients survived beyond age 40 years. Six died during follow-up at a
      mean age of 31 years (+/- 12.1 SD). Eight group A patients were in New York Heart
      Association class II, and 8 were in class III. Of the 26 group A and B patients,
      20 had aortic regurgitation, which was moderate or severe in 10. Eight had
      cardiac failure. Of 11 group A patients who remained unoperated, 5 died. Twelve
      patients were considered eligible for surgery at > or = 18 years of age. Ten
      underwent completed hemodynamic repair with a mean post-operative right
      ventricular-to-left ventricular systolic pressure ratio of 0.45 (+/- 0.16 SD),
      and there were no early or late deaths. CONCLUSIONS: Even when collateral blood
      flow permits adult survival, all such patients are symptomatic. Mean life
      expectancy without operation did not exceed three decades. Aortic regurgitation
      and cardiac failure are significant negative variables. Nearly half of unoperated
      adults died during follow-up. Staged hemodynamic repair can be performed with a
      low surgical risk in properly selected adults with PA/VSD.

PMID- 8281654
TI  - Gamma-globulin treatment of acute myocarditis in the pediatric population.
AB  - BACKGROUND: Myocardial damage in myocarditis is mediated, in part, by
      immunological mechanisms. High-dose intravenous gamma-globulin (IVIG) is an
      immunomodulatory agent that is beneficial in myocarditis secondary to Kawasaki
      disease, as well as in murine myocarditis. Since 1990, the routine management of
      presumed acute myocarditis at Children's Hospital, Boston, and Children's
      Hospital, Los Angeles, has included administration of high-dose IVIG. METHODS AND
      RESULTS: We treated 21 consecutive children presenting with presumed acute
      myocarditis with IVIG, 2 g/kg, over 24 hours, in addition to anticongestive
      therapies. A comparison group comprised 25 recent historical control patients
      meeting identical eligibility criteria but not receiving IVIG therapy. Left
      ventricular function was assessed during five time intervals: 0 to 7 days, 1 to 3
      weeks, 3 weeks to 3 months, 3 to 6 months, and 6 to 12 months. At presentation,
      the IVIG and non-IVIG groups had comparable left ventricular enlargement and poor
      fractional shortening. Compared with the non-IVIG group, those treated with IVIG
      had a smaller mean adjusted left ventricular end-diastolic dimension and higher
      fractional shortening in the periods from 3 to 6 months (P = .008 and P = .033,
      respectively) and 6 to 12 months (P = .072 and P = .029, respectively). When
      adjusting for age, biopsy status, intravenous inotropic agents, and angiotensin
      converting enzyme inhibitors, patients treated with IVIG were more likely to
      achieve normal left ventricular function during the first year after presentation
      (P = .03). By 1 year after presentation, the probability of survival tended to be
      higher among IVIG-treated patients (.84 versus .60, P = .069). We observed no
      adverse effects of IVIG administration. CONCLUSIONS: These data suggest that use
      of high-dose IVIG for treatment of acute myocarditis is associated with improved
      recovery of left ventricular function and with a tendency to better survival
      during the first year after presentation.

PMID- 8281655
TI  - Intravascular ultrasound of coronary arteries in children. Assessment of the wall
      morphology and the lumen after Kawasaki disease.
AB  - BACKGROUND: The long-term clinical issue in Kawasaki disease (KD) concerns the
      coronary artery lesion. Two-dimensional echocardiography and coronary angiography
      are routine examinations to evaluate the coronary lesions; however, these are not
      adequate to assess the wall morphology of the coronary artery (CA). Intravascular
      ultrasound imaging (IVUS), a new technology for the evaluation of the coronary
      artery lumen and wall morphology in vivo, was performed for patients after KD in
      their long-term follow-up, and we examined the new insights it gave. METHODS AND
      RESULTS: IVUS was performed during cardiac catheterization in 20 subjects (10
      patients after KD who still had coronary aneurysms or regressed coronary
      aneurysms, 2 after KD who had no coronary abnormal lesion, and 8 control patients
      with congenital heart disease and normal CA). We evaluated the wall structure at
      10 to 15 sites of the CA in each patient. IVUS was performed with a commercially
      available ultrasound imaging catheter. Four sites of a CA aneurysm in KD
      demonstrated a markedly dilated lumen without thickened intima. One site of a CA
      aneurysm with calcification demonstrated an asymmetrical lumen by a dense echo
      with acoustic shadows. Twenty-two sites of a regressed CA aneurysm demonstrated a
      marked symmetrical or asymmetrical thickening of the intima with a dense echo, in
      which the size of the lumen was similar to that at a site near a regressed
      aneurysm. The sites of angiographically normal CA revealed normal structures and
      a thin intima in many instances. Nine of 28 sites in KD with a CA abnormal
      lesion, particularly near a coronary aneurysm or regressed aneurysm, demonstrated
      a mild thickening of the intima. All the 10 sites in KD without a CA abnormal
      lesion and all the 25 sites in patients with congenital heart disease with normal
      CA demonstrated a smooth intima. CONCLUSIONS: This study demonstrated that the
      site of a regressed coronary aneurysm has a markedly thickened but smooth intima.
      The sites of angiographically normal CA after KD with or without a coronary
      lesion demonstrated normal IVUS findings in most instances but in some cases
      revealed a mild intimal thickening. IVUS is useful to evaluate the CA wall
      morphology and may contribute to the assessment of long-term CA sequelae and the
      possible development of arteriosclerotic changes in KD.

PMID- 8281656
TI  - Reconsideration of criteria for the Fontan operation. Influence of pulmonary
      artery size on postoperative hemodynamics of the Fontan operation.
AB  - BACKGROUND: The outcome of the Fontan operation largely depends on patient
      selection because this procedure is a physiological correction. Among the several
      selection criteria for the Fontan operation, the importance of adequate size of
      the pulmonary artery remains controversial. To clarify whether or not pulmonary
      artery size is indispensable as one of the selection criteria for the Fontan
      operation, we considered the physiological importance of pulmonary artery size
      and investigated how pulmonary artery size influenced postoperative hemodynamics
      of the Fontan operation. METHODS AND RESULTS: In congenital heart disease of
      decreasing pulmonary blood flow, 40 patients were examined for this analysis.
      Pulmonary artery indexes (cross-sectional area of the right and left pulmonary
      arteries divided by body surface area) were measured as the expression of
      pulmonary artery size, and the relations of pulmonary artery index (PAI) to
      pulmonary vascular resistance (Rp) and compliance (Cp) were studied. There was no
      significant correlation between PAI and Rp, whereas a significant correlation was
      found between PAI and Cp (r = .71, P = .001). Furthermore, Cp influenced
      postoperative hemodynamics of the Fontan operation by affecting peak central
      venous pressure and total impedance, which was the afterload to the ventricle.
      Impedance increased abruptly when PAI was less than approximately 100 mm2/m2.
      CONCLUSIONS: The smaller pulmonary artery size is hemodynamically disadvantageous
      after the Fontan operation, with resultant rise in peak control venous pressure
      and increased afterload to the single ventricle.

PMID- 8281657
TI  - Intracoronary ultrasound assessment of morphological and functional abnormalities
      associated with cardiac allograft vasculopathy.
AB  - BACKGROUND: The diffuse nature of cardiac allograft vasculopathy makes early
      detection of the disease by traditional noninvasive methods or coronary
      angiography difficult. The aim of this study was to determine if there is a
      relation between abnormalities in vessel wall morphology, as assessed by
      intracoronary ultrasound, and a decreased vasodilatory response to the
      endothelium-dependent vasodilator papaverine hydrochloride and if cardiac
      allograft vasculopathy detected by coronary angiography is associated with
      specific intracoronary ultrasound findings. METHODS AND RESULTS: Twenty-three
      heart transplant recipients underwent 25 intracoronary ultrasound studies and 24
      studies of coronary vasomotor tone 10 days to 8.3 years after surgery using a 20
      mHz intracoronary ultrasound catheter. The studies were divided in two groups
      according to the presence (n = 7, group 1) or absence (n = 18, group 2) of
      angiographically evident cardiac allograft vasculopathy. Qualitative assessment
      of vessel wall morphology and quantitative analysis of the vasodilator response
      to the injection of papaverine hydrochloride into the coronary artery distal to
      the imaging site were performed off-line, and results for the two study groups
      were compared. A significantly higher percentage of patients with than without
      angiographic evidence of cardiac allograft vasculopathy had a three-interface
      vessel wall morphology by intracoronary ultrasound (100% versus 11%, P < .001).
      In two recipients who underwent two serial studies, the appearance of three
      interfaces in the vessel wall or a progressive thickening of the inner interface
      of the vessel wall occurred in conjunction with the appearance of angiographic
      cardiac allograft vasculopathy. The vasodilator response to papaverine was less
      in patients with than in those without angiographically evident cardiac allograft
      vasculopathy both in terms of absolute and relative increases in lumen diameter
      (+0.1 +/- 0.12 mm versus +0.3 +/- 0.17 mm, P < .05, and +5.1 +/- 5.3% versus +8.2
      +/- 5.3%, P = NS) and lumen cross-sectional area (+0.5 +/- 0.6 mm2 versus +1.7 +/
      1.1 mm2, P < .02, and +7.1 +/- 8.8% versus 16.6 +/- 11.0%, P = .055),
      respectively. CONCLUSIONS: Intracoronary ultrasound assessment of vessel wall
      morphology and evaluation of vascular response to endothelium-dependent
      vasodilators are useful techniques for detecting cardiac allograft vasculopathy.

PMID- 8281658
TI  - Myocardial perfusion and ventricular function measurements during total coronary
      artery occlusion in humans. A comparison with rest and exercise radionuclide
      studies.
AB  - BACKGROUND: The purpose of this investigation was to compare the magnitude of
      change in myocardial perfusion and function during exercise with that obtained
      during total coronary artery occlusion. Radionuclide studies are widely used for
      the diagnosis and determination of prognosis in patients with suspected or known
      coronary artery disease. These studies are based on the premise that the relative
      deficit of coronary blood flow, which is induced by exercise and recognized as
      increased demand, relates to the jeopardy experienced by the decrease or sudden
      absolute interruption of coronary blood flow that is recognized as decreased
      supply and is associated with coronary stenosis or total coronary artery
      occlusion. The magnitude of exercise-induced perfusion and function abnormalities
      compared with those induced by total coronary artery occlusion in humans has not
      been previously reported. METHODS AND RESULTS: We prospectively studied 20
      patients with > or = 50% diameter stenosis documented by quantitative coronary
      angiography in at least one vessel. A same-day rest/exercise sestamibi myocardial
      function and perfusion study was performed within 24 hours before percutaneous
      transluminal coronary angioplasty. At 1 minute after balloon inflation, while the
      vessel was occluded, sestamibi was injected, and a myocardial perfusion and
      function study was performed. Perfusion defect size was greater during occlusion
      (28 +/- 3%) than during exercise (13 +/- 2%) (P < .01). Ejection fraction was
      greater during exercise (53 +/- 3%) compared with values measured during
      occlusion (41 +/- 2%) (P < .01). CONCLUSIONS: Physiological abnormalities induced
      by coronary occlusion are greater than those that occur during exercise, thereby
      indicating that stress-induced ischemia may not reflect the total potential
      myocardium in jeopardy from a stenotic lesion, if sudden occlusion occurs.

PMID- 8281659
TI  - Fast computed tomography detection of coronary calcification in the diagnosis of
      coronary artery disease. Comparison with angiography in patients < 50 years old.
AB  - BACKGROUND: The predominant cause of coronary artery calcification is
      atherosclerosis. Although fast x-ray computed tomography (CT) has been
      demonstrated to be a sensitive technique to detect coronary calcification, the
      increasing prevalence of calcification with age has been associated with a low
      specificity for identifying obstructive atherosclerosis. We hypothesized that the
      specificity of this test would be improved in a younger patient population,
      making it more useful in the diagnosis of coronary artery disease. METHODS AND
      RESULTS: We compared fast CT-detected calcification with coronary angiography in
      106 patients under the age of 50 years. Nonenhanced fast CT scans consisting of
      20 contiguous 3-mm tomograms of the proximal coronary arteries were obtained
      during a single breath hold. A positive scan was defined as 4 contiguous voxels
      (> or = 1 mm2) of density > 130 Hounsfield units in the region of the epicardial
      coronary arteries. Calcification detected by fast CT had an 85% sensitivity to
      predict patients with significant coronary artery disease (> or = 50% diameter
      stenosis), with a specificity of 45%. Although the sensitivity to detect
      multivessel disease was 94%, the sensitivity to detect single-vessel disease was
      75%. Changing the threshold for defining a positive fast CT scan from 4 to 2
      contiguous voxels produced a small improvement in sensitivity, to 88%, but
      reduced specificity to 36%. CONCLUSIONS: Although the specificity to detect
      angiographically significant coronary disease with fast CT improves in a younger
      patient population, it continues to be relatively low. In contrast to older
      patient populations, a small but significant number of patients < 50 years old
      with angiographically significant coronary artery disease do not have coronary
      calcification demonstrated by fast CT. Thus, caution should be used in excluding
      significant coronary artery disease on the basis of a negative fast CT study.

PMID- 8281660
TI  - A comparison of low- with high-osmolality contrast agents in cardiac angiography.
      Identification of criteria for selective use.
AB  - BACKGROUND: Controversy exists as to whether low-osmolality radiographic contrast
      agents, which have less detrimental pharmacological effects but are considerably
      more expensive than high-osmolality agents, should be used universally or only
      for selected high-risk patients. METHODS AND RESULTS: A randomized, double-blind
      study was used to compare the frequency and severity of adverse events in 2245
      consecutive patients undergoing diagnostic cardiac angiography. Two thousand one
      hundred sixty-six patients were successfully randomized to either iohexol, a low
      osmolality contrast agent, or diatrizoate (as Hypaque 76), a high-osmolality
      agent. The end point event included clinically important adverse events (which
      jeopardized the patient or required aggressive treatment), contrast agent-related
      procedure abbreviations, and conversion to open-label contrast agent. Clinically
      important end point events were associated with increased age, New York Heart
      Association functional class, left ventricular end-diastolic pressure,
      arteriovenous oxygen difference, severity of coronary artery disease, and history
      of a previous reaction to contrast agent. End point events were less frequent in
      patients receiving iohexol (2.6% versus 4.6%; adjusted odds ratio, 1.59; 95%
      confidence interval, 0.97-2.60; P = .07). The difference in event frequency
      between iohexol and diatrizoate was confined to the highest-risk quartile of the
      patient population. An algorithm was developed to classify patients as being at
      high or low risk for an event based on patient age, New York Heart Association
      class, history of a prior contrast reaction, and left ventricular end-diastolic
      pressure. Application of this algorithm for selective use of low-osmolality
      agents only for high-risk patients to a theoretical population of 1000 patients
      reduced contrast agent costs 66% without increasing the frequency of contrast
      agent-related adverse events. CONCLUSIONS: The advantages of low-osmolality
      contrast agents are clinically important in patients with severe heart disease
      but are not in less ill patients. Universal use of low-osmolality agents for
      cardiac angiography in an unselected population is not necessary. Appropriately
      guided selective use of low-osmolality contrast agents is feasible and has the
      potential to reduce cost substantially without compromising safety or
      effectiveness.

PMID- 8281661
TI  - Antiplatelet and antithrombotic efficacy of DMP 728, a novel platelet GPIIb/IIIa
      receptor antagonist.
AB  - BACKGROUND: Currently used antiplatelet drugs, including aspirin, ticlopidine,
      and others, are effective against certain but not all of the many endogenous
      platelet activators. Because of their limited efficacy, a significant number of
      serious thromboembolic complications still occur, highlighting the need for a
      more effective therapy. Thus, we have identified a systemically active peptide
      analogue (DMP 728) of the arginine-glycine-aspartic acid (RGD) recognition
      sequence that mediates the binding of ligands such as fibrinogen to the platelet
      glycoprotein (GP) IIb/IIIa receptors. The goals of the present study were to
      determine the antiplatelet and antithrombotic efficacies of DMP 728 in various
      arterial thrombosis models. METHODS AND RESULTS: DMP 728 demonstrated
      antiplatelet efficacy in vitro in inhibiting ADP-induced human platelet
      aggregation (IC50, 46 +/- 2 nmol/L) and fibrinogen binding to human platelets
      (IC50, 2.3 +/- 0.8 nmol/L) or purified human GPIIb/IIIa receptors (IC50, 0.6 +/-
      0.1 nmol/L). DMP 728 demonstrated high affinity and specificity for human
      platelet GPIIb/IIIa over other adhesion molecules. In anesthetized mongrel dogs,
      DMP 728 at 0.001 to 1.0 mg/kg IV produced dose-dependent antiplatelet effects in
      inhibiting ex vivo platelet aggregation induced by ADP and in prolonging template
      bleeding time. DMP 728 effects on bleeding time prolongation were more rapidly
      reversible than those on platelet aggregation inhibition. A maximal antiplatelet
      effect for DMP 728 was demonstrated at 0.01 mg/kg IV bolus. The antithrombotic
      efficacy of DMP 728 was examined in vitro and in vivo after IV administration at
      different doses in various models of arterial thrombosis. In the coronary artery
      Folts model in dogs, DMP 728 demonstrated maximal antithrombotic efficacy at 0.01
      mg/kg IV bolus with an ED50 of 0.005 mg/kg IV bolus in inhibiting cyclic flow
      reductions. Additionally, DMP 728 demonstrated 100% prevention of primary
      thrombosis and rethrombosis (P < .01) after treatment with different
      thrombolytics, including tissue plasminogen activator and streptokinase, in an
      electrolytically induced femoral artery thrombosis model in dogs. CONCLUSIONS:
      Acute intravenous DMP 728 administration (0.001 to 1.0 mg/kg) has dose-dependent
      antiplatelet and antithrombotic effects in different arterial thrombosis models.
      These data suggest that DMP 728, a low-molecular-weight GPIIb/IIIa receptor
      antagonist, may have therapeutic potential as an effective antithrombotic agent
      in coronary and peripheral artery thromboembolic disorders.

PMID- 8281662
TI  - Clinical and angiographic results of transluminal extraction coronary atherectomy
      in saphenous vein bypass grafts.
AB  - BACKGROUND: Transluminal extraction coronary (TEC) atherectomy is a relatively
      new device that has recently been approved by the Food and Drug Administration.
      Because of its ability to aspirate clot and atheromatous material, TEC
      atherectomy may be useful in patients with stenoses in saphenous vein bypass
      grafts. METHODS AND RESULTS: TEC atherectomy was performed on 158 saphenous vein
      graft lesions in 146 consecutive patients with a mean age of 65 +/- 8 years (78%
      men). Clinical indications for atherectomy included stable angina (37%), unstable
      angina (54%), and postinfarction angina after recent (< 1 month) myocardial
      infarction (8%). Patients with acute myocardial infarction and target vessels < 2
      mm in diameter were excluded. The mean age of the bypass graft was 8.3 +/- 3.0
      years, and 17% were diffusely diseased and degenerated. Complex lesion morphology
      included total occlusion (6%), eccentricity (64%), ulceration (18%), and thrombus
      (28%). The TEC atherectomy cutter was successfully advanced through 144 lesions
      (91%), but technical failures occurred in 14 lesions (9%), and these were
      subsequently managed by successful balloon angioplasty. Quantitative angiography
      revealed an increase in lumen diameter from 0.9 +/- 0.5 mm, to 1.5 +/- 0.7 mm
      after TEC atherectomy, to 2.3 +/- 0.8 mm after percutaneous transluminal coronary
      angioplasty (PTCA) (P < .001), which corresponded to decreases in diameter
      stenosis from 75 +/- 14%, to 58 +/- 20% after TEC atherectomy, to 36 +/- 22%
      after PTCA (P < .001). Device success was achieved in 39.2% (post-TEC atherectomy
      decrease in diameter stenosis > or = 20%), and procedural success was achieved in
      84% (final diameter stenosis < 50% in the absence of a major complication).
      Angiographic complications were evident in 33 lesions (20.7%) immediately after
      TEC atherectomy and in 8 lesions (5%) after PTCA, including distal embolization
      (11.9%), no-reflow (8.8%), and abrupt closure (5.0%), but no perforations.
      Adjunctive PTCA (and other medical therapy) successfully managed 61% of
      angiographic complications. Serious clinical complications included in-hospital
      death in 3 patients (2.0%), emergency bypass surgery in 1 patient who died
      (0.7%), Q wave myocardial infarction in 3 patients (2.0%), non-Q wave myocardial
      infarction in 4 patients (2.7%), vascular injury requiring surgical repair and/or
      blood transfusion in 9 patients (6.1%), and hemorrhagic cerebral infarction in 4
      patients (2.7%). Using a composite clinical end point defined as in-hospital
      death, emergency bypass surgery, or myocardial infarction, the strongest
      independent correlate (P < .001) of a severe clinical complication was the
      development of one or more serious angiographic complications (no-reflow, distal
      embolization, or abrupt closure) immediately after TEC atherectomy. Complete
      clinical follow-up was available in 118 (92%) of 128 eligible patients at an
      interval of 6.0 +/- 2.5 months after discharge. Late cardiac outcome included
      recurrent angina treated with medical therapy (18%), repeat percutaneous
      intervention on the original target lesion (26%), repeat coronary artery bypass
      surgery (5%), Q wave myocardial infarction (4%), and late cardiac death (7%).
      Angiographic follow-up in 105 (80%) of 132 eligible lesions revealed a restenosis
      rate of 69% (defined as a diameter stenosis > 50%), including 30 lesions (29%)
      with total occlusion of the original lesion. CONCLUSIONS: In patients with
      stenoses in saphenous vein bypass grafts, TEC atherectomy is limited by the
      frequent need for adjunctive balloon angioplasty to achieve adequate lumen
      enlargement and to manage TEC atherectomy-induced complications. Although the
      incidence of serious clinical complications is similar to that of other
      percutaneous interventions in vein grafts, there is a high incidence of
      restenosis and late vessel occlusion. Prospective randomized studies are needed
      to determine the best revascularization strategy for high-risk patients with old
      degenerated vein

PMID- 8281663
TI  - Isoform-specific regulation of myocardial Na,K-ATPase alpha-subunit in congestive
      heart failure. Role of norepinephrine.
AB  - BACKGROUND: Myocardial ouabain-binding sites and Na,K-ATPase activity are reduced
      in congestive heart failure (CHF), but the mechanisms by which CHF reduces the
      Na,K-ATPase remain unknown. We proposed to investigate whether the changes are
      accompanied by isoform-specific reductions of the Na,K-ATPase alpha-subunit
      proteins in CHF and whether similar changes could be produced by exogenous
      norepinephrine administration. METHODS AND RESULTS: CHF was induced in dogs by
      rapid ventricular pacing at a rate of 225 beats per minute for 8 weeks (protocol
      1). A second group of dogs were paced at 100 beats per minute and served as
      controls. In protocol 2, norepinephrine was infused in normal dogs using a
      subcutaneous osmotic minipump for 8 weeks. The control dogs received normal
      saline through the pump. Animals were studied after 8 weeks of pacing or
      norepinephrine infusion. After the baseline hemodynamics and interstitial
      norepinephrine concentration had been obtained, the hearts were removed for
      measuring [3H]ouabain-binding sites and Na,K-ATPase alpha-subunit proteins using
      isoform-specific monoclonal antibodies. RESULTS: Myocardial [3H]ouabain-binding
      sites were reduced in dogs with CHF and chronic norepinephrine infusion. The
      Western blot analysis showed that adult canine hearts possess both alpha 1 and
      alpha 3 isoforms of the Na,K-ATPase alpha-subunit but not the alpha 2 isoform
      protein. CHF and NE infusion had no effect on the Na,K-ATPase alpha 1-subunit
      protein but did reduce the alpha 3 isoform protein significantly. In addition,
      there was a significant inverse correlation between the amount of myocardial
      alpha 3 isoform protein and interstitial norepinephrine content in the dogs. In
      contrast, the specific activity of the sarcolemmal marker 5'-nucleotidase did not
      differ among the groups of animals. CONCLUSIONS: The reduction of myocardial Na,K
      ATPase in CHF is limited to the alpha 3 isoform. Furthermore, because similar
      changes in myocardial ouabain-binding sites and Na,K-ATPase alpha 3 isoform were
      produced by chronic norepinephrine infusion, the decrease in the Na,K-ATPase in
      CHF is most likely mediated via excess sympathetic stimulation.

PMID- 8281664
TI  - Augmentation of the synthesis of plasminogen activator inhibitor type-1 by
      precursors of insulin. A potential risk factor for vascular disease.
AB  - BACKGROUND: Both vascular disease and elevated concentrations in plasma of
      plasminogen activator inhibitor type-1 (PAI-1) are prominent in patients with non
      insulin-dependent diabetes mellitus (NIDDM). We and others have hypothesized that
      the increased PAI-1 may contribute to acceleration of atherosclerosis in this
      condition and in other states characterized by insulin resistance as well.
      Surprisingly, however, elevations of PAI-1 decrease when type II diabetic
      patients are treated with exogenous insulin, as do circulating concentrations of
      the precursor of insulin, proinsulin, in plasma. Accordingly, the increased PAI-1
      in patients with NIDDM may reflect effects of precursors of insulin rather than
      or in addition to those of insulin itself. To assess this possibility directly,
      this study was performed to identify potential direct effects of proinsulin and
      proinsulin split products on synthesis of PAI-1 in liver cells, thought to be the
      major source of circulating PAI-1 in vivo. METHODS AND RESULTS: Hep G2 cells
      (highly differentiated human hepatoma cells) were exposed to human proinsulin,
      des(31,32)proinsulin and des(64,65)proinsulin (split products of proinsulin), or
      C-peptide. Accumulation of PAI-1 in conditioned media increased in a time- and
      concentration-dependent fashion in response to the two des-intermediates [3.3
      fold with des(31,32)proinsulin and 4.5-fold with des(64,65)proinsulin]. C-peptide
      elicited no increase. Stimulation was transduced at least in part by the insulin
      receptor as shown by inhibition of stimulation by insulin receptor antibodies,
      mediated at the level of PAI-1 gene expression as shown by the 2.2- to 2.9-fold
      increases in steady-state concentrations of PAI-1 mRNA, and indicative of newly
      synthesized protein as shown by results in metabolic labeling experiments.
      CONCLUSIONS: Our results are consistent with the hypothesis that precursors of
      insulin (proinsulin and proinsulin split products), known to be present in
      relatively high concentrations in plasma in patients with NIDDM and conditions
      characterized by insulin resistance, may directly stimulate PAI-1 synthesis,
      thereby attenuating fibrinolysis and accelerating atherogenesis.

PMID- 8281665
TI  - An evaluation of ribonuclease protection assays for the detection of beta-cardiac
      myosin heavy chain gene mutations.
AB  - BACKGROUND: Ribonuclease (RNase) protection has been used to identify beta
      cardiac myosin heavy chain (MHC) gene mutations that cause familial hypertrophic
      cardiomyopathy (FHC). Since more than 10 different mutations within this gene
      have been demonstrated to cause FHC in unrelated individuals, the genetic
      diagnosis of this condition will involve screening the beta-MHC gene. The
      accuracy with which RNase protection identifies such mutations is critical to
      defining the utility of this methodology in detecting mutations that cause FHC.
      METHODS AND RESULTS: Twelve unrelated individuals with FHC were selected for
      further study because their beta-MHC genes had been screened for mutations by use
      of RNase protection, and no mutation was found. We performed linkage analysis of
      the families of these 12 probands using polymorphic short tandem repeats within
      the beta-MHC gene to determine whether FHC was genetically linked to the MHC
      locus on chromosome 14. FHC was not genetically linked to the MHC locus in 11
      families whose beta-cardiac MHC gene did not contain mutations detectable by
      RNase protection. CONCLUSIONS: We conclude that RNase protection is a sensitive
      method for screening for mutations within the beta-cardiac MHC gene. Further,
      mutations in the noncoding regions of the beta-MHC gene and mutations in the
      alpha-cardiac MHC gene are not a common cause of FHC. Negative RNase protection
      assays of affected individuals suggest that their FHC is due to mutations at
      other loci.

PMID- 8281666
TI  - Interaction between plasma potassium and epinephrine in coronary thrombosis in
      dogs.
AB  - BACKGROUND: Both plasma potassium ([K]) and epinephrine concentrations have been
      known to increase during exercise and decrease rapidly shortly after exercise; in
      addition, it is also known that exercise can promote coronary thrombosis in human
      and animal subjects. Many studies have shown that epinephrine has a stimulatory
      effect on coronary thrombosis; however, little information is available
      concerning the effect of raising plasma [K] on coronary thrombosis. The present
      study was designed to investigate the effect of raising plasma [K] and its
      interaction with epinephrine infusion on coronary thrombosis. METHODS AND
      RESULTS: A canine model of coronary thrombosis was used, and the frequency of
      cyclic blood flow reductions (CFRs) resulting from thrombus formation in the
      circumflex artery was analyzed in the study. By acutely raising plasma [K] to
      approximately 6.0 mEq/L, the frequency of CFRs was reduced from 8.0 +/- 0.6 to
      3.7 +/- 1.0 in 40 minutes (P < .01). Epinephrine infusion (0.5 microgram.kg-1 x
      min-1) stimulated the frequency of CFRs from 7.1 +/- 0.5 to 11.5 +/- 0.7 in 40
      minutes (P < .01). However, if plasma [K] was raised to approximately 6.0 mEq/L
      while the epinephrine infusion was continued, the frequency fell from 11.5 +/-
      0.7 to 7.7 +/- 1.1 in 40 minutes (P < .01). CONCLUSIONS: The present study
      demonstrated that acutely raising plasma [K] inhibited coronary thrombosis in
      dogs and also blocked the potentiating effect of epinephrine on coronary
      thrombosis. These findings may suggest that raising plasma [K] exerts a
      protective effect against coronary thrombosis and that a rapid decrease in plasma
      [K], such as that occurring shortly after exercise, facilitates coronary artery
      thrombosis when the artery has a preexisting pathological condition.

PMID- 8281667
TI  - Does external ultrasound accelerate thrombolysis? Results from a rabbit model.
AB  - BACKGROUND: Prior in vitro and in vivo studies have reported that external
      ultrasound accelerates thrombolysis at intensities too low to have a direct
      effect on clot dissolution in the absence of a thrombolytic agent. The present
      study was undertaken to examine the ultrasound effect on thrombolysis and
      reocclusion in a rabbit thrombosis model. METHODS AND RESULTS: Blood clots were
      produced in a femoral artery segment with endothelial damage and distal stenosis.
      Recombinant tissue-type plasminogen activator (rTPA) was infused at 30
      micrograms.kg-1.min-1 for 60 minutes. Femoral artery flow was measured every 5
      minutes for 2 hours. Rabbits were randomized to four groups with continuous wave
      ultrasound on or off with or without intravenous injection of 17 mg/kg aspirin
      (+US/-US/+Asp/-Asp). Ultrasound frequency and intensity were 1 MHz and 6.3 W/cm2.
      In seven of eight and five of five rabbits given rTPA and -US/-Asp or -US/+Asp,
      respectively, reflow was observed, persisting to the end of the observation
      period. In five of nine and four of five rabbits given rTPA and +US/-Asp or
      +US/+Asp, reflow was achieved, but persistent reocclusion was subsequently
      observed in five of five and two of four of these rabbits, respectively. Overall,
      femoral artery patency was worse and reocclusion occurred more often when
      ultrasound was added to rTPA (P = .002 by nonparametric ANOVA). However, initial
      reflow occurred more rapidly with ultrasound exposure (21 +/- 10 and 33 +/- 6
      minutes for the +US/+Asp and +US/-Asp groups, respectively) compared with without
      ultrasound (46 +/- 13 and 74 +/- 14 minutes for the -US/+Asp and -US/-Asp groups,
      respectively) (P = .03 by ANOVA). CONCLUSIONS: Although time to initial reflow
      was shortened by ultrasound, it was associated with less reperfusion and more
      reocclusion in this model. A possible explanation for these results is ultrasound
      induced platelet activation counterbalancing its thrombolysis-accelerating
      effect.

PMID- 8281668
TI  - Serial echocardiographic assessment of left ventricular geometry and function
      after large myocardial infarction in the rat.
AB  - BACKGROUND: The development of heart failure after acute myocardial infarction
      (MI) may be related to alterations of left ventricular (LV) structure and
      function. Pathological LV remodeling may exacerbate systolic and diastolic
      dysfunction because increased cavity dimensions tend to increase LV wall stress.
      Unfortunately, many complicating factors have made it difficult to clearly define
      the time course of LV remodeling after myocardial infarction in patients, and the
      contribution of structural changes to altered function has not been fully
      explored. METHODS AND RESULTS: To determine the type, magnitude, and time course
      of changes in LV geometry and function, we performed transthoracic Doppler
      echocardiographic examinations in rats before and 1 and 6 weeks after transmural
      MI induced by coronary ligation. LV internal diastolic dimension was greater in
      infarcted than in sham-operated rats at 1 and 6 weeks after MI (9.4 +/- 0.6
      versus 8.0 +/- 0.5 and 10.1 +/- 0.9 versus 8.5 +/- 0.9 mm, respectively; P < .05
      compared with sham-operated rats). There was significant thinning of the
      infarcted anterior wall at 1 and 6 weeks (0.99 +/- 0.2 versus 1.33 +/- 0.19 and
      0.96 +/- 0.22 versus 1.51 +/- 0.18 mm, P < .05), while the thickness of the
      noninfarcted posterior wall increased but was not different from normal growth in
      sham-operated rats. Six weeks after surgery, fractional shortening was impaired
      (11 +/- 5% versus 35 +/- 5%, P < .05), and systolic thickening of the
      noninfarcted posterior wall was depressed (38 +/- 9% versus 67 +/- 18%, P < .05)
      in infarcted rats compared with shams. These changes in structure and systolic
      function were accompanied by progressive alterations in LV diastolic filling.
      Peak early filling velocity increased at 1 and 6 weeks in MI rats (91 +/- 9
      versus 79 +/- 9 and 100 +/- 14 versus 74 +/- 11 cm/s, P < .05), and the
      deceleration rate of the early filling wave was more rapid in rats with MI (21.6
      +/- 5.0 versus 15.6 +/- 3.1 and 26.1 +/- 9.8 versus 11.2 +/- 2.7 m/s2, P < .05).
      Late filling velocity was decreased (16 +/- 15 versus 33 +/- 7 and 15 +/- 18
      versus 34 +/- 5 cm/s, P < .05), resulting in a marked increase in the ratio of
      early to late filling. The peak velocity and the velocity-time integral of LV
      outflow did not change after MI. CONCLUSIONS: Postinfarction LV remodeling in the
      rat is characterized by progressive cavity dilatation, inadequate hypertrophy of
      the surviving myocardium, the gradual development of regional contractile
      dysfunction in noninfarcted segments, and marked abnormalities of diastolic
      filling. These changes can be tracked longitudinally with transthoracic
      echocardiography.

PMID- 8281669
TI  - Heat-shock protein induction in rat hearts. A direct correlation between the
      amount of heat-shock protein induced and the degree of myocardial protection.
AB  - BACKGROUND: Previous studies have demonstrated that heat-shock treatment results
      in the induction of 72-kD heat-shock protein (HSP72) and a reduction of infarct
      size after subsequent ischemia and reperfusion. METHODS AND RESULTS: To test the
      hypothesis that the degree of protection from ischemic injury in heat-shocked
      rats correlates with the degree of prior HSP72 induction, rats pretreated with 40
      degrees C, 41 degrees C, or 42 degrees C of whole-body hyperthermia followed by
      24 hours of recovery and control rats (n = 6 in each group) were quantitatively
      assessed for the presence of myocardial HPS72 by optical densitometry of Western
      blots and a primary antibody that is specific for HSP72 and a tertiary antibody
      labeled with 125I. Although rats heat-shocked to 40 degrees C had no significant
      induction of myocardial HSP72, rats heat-shocked to 41 degrees C and 42 degrees C
      demonstrated progressively increased amounts of myocardial HSP72 compared with
      controls. Separate groups of rats heat-shocked to 40 degrees C (n = 16), 41
      degrees C (n = 37), and 42 degrees C (n = 36) with 24 hours of recovery and
      controls (n = 26) were subjected to 35 minutes of left coronary artery occlusion
      and 120 minutes of reperfusion. Compared with control and 40 degrees C rats,
      there was progressive infarct size reduction, assessed by triphenyltetrazolium
      chloride staining, in rats that were heat-shocked to 41 degrees C and 42 degrees
      C. Furthermore, there was a direct correlation between the amount of HSP72
      induced and the reduction in infarct size (r = .97, P = .037). CONCLUSIONS: These
      results suggest that the improved salvage after heat-shock pretreatment may be
      related to the amount of HSP72 induced before prolonged ischemia and reperfusion.

PMID- 8281670
TI  - Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques
      is characterized by an inflammatory process irrespective of the dominant plaque
      morphology.
AB  - BACKGROUND: The study was designed to verify the concept of plaques "at risk" and
      whether inflammation could play a role in plaque rupture and thrombosis. METHODS
      AND RESULTS: In 20 patients who had died of acute myocardial infarction, the
      thrombosed coronary artery was identified and the site of plaque rupture was
      traced in serial sections. The cellular characteristics of the fibrous cap at the
      immediate site of rupture were analyzed and compared with the adjacent cap tissue
      by use of monoclonal antibodies reactive with macrophages, T lymphocytes, and
      smooth muscle cells. A deep intimal rupture, extending into the lipid core, was
      encountered in 12 plaques, whereas 8 had superficial erosions only. Ten
      atherosclerotic plaques had a distinctly attenuated fibrous cap covering a large
      atheroma, 7 showed a thick fibrocellular cap overlying a lipid pool, and 3 showed
      a fibrocellular lesion without a clear lipid core. Macrophages, and to a lesser
      extent T lymphocytes, were the dominant cells at the immediate site of either
      rupture or superficial erosion in each instance. These sites, moreover, were
      always characterized by abundant expression of HLA-DR antigens on both
      inflammatory cells and adjacent smooth muscle cells, suggesting an active
      inflammatory reaction. In terms of overall cellular composition of the ruptured
      plaques, the dominant cell types were macrophages and T cells in 11, smooth
      muscle cells in 3, and mixtures of both in 6. CONCLUSIONS: The underlying
      atherosclerotic plaque morphology in complicated coronary artery lesions causing
      acute myocardial infarction is heterogeneous with respect to both plaque
      architecture and cellular composition. However, the immediate site of plaque
      rupture or erosion is always marked by an inflammatory process. This suggests
      that inflammation plays a role in destabilizing the fibrous cap tissue and, thus,
      in enhancing the risk of coronary thrombosis.

PMID- 8281671
TI  - Arterial diastolic pressure augmentation by intra-aortic balloon counterpulsation
      enhances the onset of coronary artery reperfusion by thrombolytic therapy.
AB  - BACKGROUND: The early establishment of infarct artery reperfusion by intravenous
      thrombolytic therapy has improved survival after acute myocardial infarction.
      Investigations of reperfusion have focused on the effects of specific
      thrombolytic agents, anticoagulation, and platelet inhibition. However, little
      attention has been given to the relation of arterial blood pressure to
      thrombolysis, a factor that probably affects thrombolytic agent delivery to the
      obstructing thrombus. METHODS AND RESULTS: The effect of arterial diastolic
      pressure augmentation by intra-aortic balloon counterpulsation (IABP) on
      reperfusion after intravenous thrombolytic therapy was studied in a canine model.
      A critical left anterior descending coronary artery stenosis was created by an
      occluder. Acute thrombosis immediately proximal to the occluder was formed by
      local injection of a blood and thrombin mixture into a segment of the artery that
      had intimal damage (groups 1 through 3). Continuous coronary blood flow velocity
      was measured by an epicardial Doppler probe. Group 1 (n = 7) served as control.
      Group 2 (n = 6) received an intravenous, front-loaded recombinant tissue-type
      plasminogen activator (rTPA) regimen (1.25 mg/kg total dose, 15% as bolus, 50% in
      the first 30 minutes, and 35% for the following 60 minutes). Group 3 (n = 6)
      received the same rTPA regimen with IABP beginning at the start of rTPA
      administration. Coronary blood flow velocity, arterial pressure, and heart rate
      were observed for 150 minutes after the start of thrombolytic therapy. Five
      animals did not undergo coronary thrombosis (group 4) and had coronary blood flow
      velocity determined before and after IABP at baseline and after creation of
      critical stenosis. Mean systolic arterial blood pressure and heart rate were not
      statistically different between groups. Peak augmented diastolic pressure by IABP
      was 97.9 +/- 1.3% of systolic pressure in group 3 dogs. Spontaneous reperfusion
      did not occur in any group 1 dogs. All animals treated with rTPA reperfused.
      Reperfusion occurred in group 3 (13.1 +/- 2.1 minutes) earlier than in group 2
      (39.2 +/- 9.4 minutes, P = .02). Overall duration of arterial patency did not
      differ between group 2 (81.4 +/- 16.6 minutes) and group 3 (94.9 +/- 15.3
      minutes, P = .52). Reocclusions occurred with similar frequency (P = .85) in
      groups 2 and 3. In group 4, IABP did not increase baseline coronary blood flow
      velocity. CONCLUSIONS: This study demonstrates that augmentation of diastolic
      arterial pressure by IABP enhances thrombolysis, leading to faster reperfusion.
      This effect appears to be unrelated to an increase in coronary blood flow and may
      be due to an effect of the augmented diastolic blood pressure wave on the
      obstructing thrombus. These findings suggest that the time to reperfusion by rTPA
      may be blood pressure dependent. The relation of arterial blood pressure to
      successful thrombolysis may have important implications for future treatment
      strategies for myocardial infarction.

PMID- 8281672
TI  - Effect of calcitonin gene-related peptide on coronary microvessels and its role
      in acute myocardial ischemia.
AB  - BACKGROUND: Calcitonin gene-related peptide (CGRP) is a potent dilator of
      epicardial conduit vessels and is released during myocardial ischemia in humans.
      However, the effect of CGRP on coronary arterial microvessels is still unclear,
      and it is unknown if CGRP modulates the tone of coronary arterial microvessels
      during acute myocardial ischemia. METHODS AND RESULTS: Epimyocardial microvessels
      were observed through a microscope equipped with a floating objective system in
      anesthetized open-chest dogs. Heart rate and aortic pressure were maintained at
      control levels. Flow velocity of the left anterior descending coronary artery
      (LAD) was measured with a suction-cup Doppler probe. When CGRP was cumulatively
      infused into the LAD (0.05, 0.5, 5.0, and 50 pmol/kg per minute) or superfused
      (0.03, 0.3, 3.0, and 30 nmol/L) over the left ventricular surface, arterial
      control microvessels > 100 microns in diameter dilated dose dependently at
      dosages of 0.5 to 50 pmol/kg per minute (infused) or 0.3 to 30 nmol/L
      (superfused), but those < 100 microns dilated only at the highest dose, and those
      > 100 microns had greater dilation in both groups. Only the highest dose of CGRP
      (infused) significantly increased coronary flow. The superfusion of CGRP(8-37)
      (CGRP receptor antagonist, 300 nmol/L) did not affect the control diameters of
      coronary arterial microvessels but completely abolished CGRP-induced vasodilation
      at the same doses (infused and superfused). However, 300 nmol/L of CGRP(8-37) did
      not affect the response of coronary arterial microvessels to the LAD occlusion in
      any size. CONCLUSIONS: CGRP preferentially dilates the coronary arterial
      microvessels > 100 microns in diameter but has only a small effect on those < 100
      microns. Endogenous CGRP does not modulate the tone of coronary arterial
      microvessels during acute myocardial ischemia in beating canine hearts.

PMID- 8281673
TI  - Nitric oxide mediates flow-dependent epicardial coronary vasodilation to changes
      in pulse frequency but not mean flow in conscious dogs.
AB  - BACKGROUND: Although epicardial coronary arteries dilate in response to changes
      in flow, the mechanisms responsible for this and the mechanical stimuli that are
      sensed by the endothelium are not completely defined. We performed the present
      study to determine the importance of nitric oxide in eliciting epicardial
      dilation to sustained changes in mean flow and pulse frequency in the coronary
      circulation of conscious dogs. METHODS AND RESULTS: Dogs were chronically
      instrumented with a circumflex coronary occluder, piezoelectric crystals to
      measure epicardial diameter, and a coronary artery catheter placed distal to the
      crystals for intracoronary drug infusion. Studies were conducted in dogs in the
      conscious state. We inhibited nitric oxide production by administering the
      arginine analog N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg IV),
      which attenuated the epicardial artery diameter changes to left atrial infusions
      of acetylcholine (10 micrograms/min) from 140 +/- 23 (+/- SEM) to 46 +/- 20
      microns (P < .05). Epicardial dilation to sustained increases in mean coronary
      artery at a constant heart rate. Intracoronary adenosine increased mean flow to
      the same extent (180 +/- 21 versus 177 +/- 24 mL/min after L-NAME, P = NS), but
      inhibiting nitric oxide production had no effect on flow-mediated epicardial
      dilation, with coronary diameter increasing by 264 +/- 36 microns under control
      conditions and 294 +/- 67 microns after L-NAME (P = NS). In contrast, when pulse
      frequency was increased by pacing to a rate of 200 beats per minute, mean
      coronary flow increased to a similar level (78 +/- 9 versus 75 +/- 9 mL/min after
      L-NAME), but the epicardial diameter change to pacing was attenuated from 170 +/-
      29 microns under control conditions to 54 +/- 23 microns after L-NAME (P < .01).
      CONCLUSIONS: These results demonstrate that in vivo, nitric oxide production is
      primarily responsible for eliciting epicardial coronary vasodilation to
      endothelium-dependent agonists and changes in coronary flow pulse frequency. The
      failure of L-NAME to affect epicardial vasodilation during sustained increases in
      mean flow when pulse frequency is held constant suggests that additional
      mechanisms are involved in flow-mediated vasodilation of epicardial coronary
      arteries.

PMID- 8281674
TI  - Angiotensin-converting enzyme inhibition with fosinopril sodium in the prevention
      of restenosis after coronary angioplasty.
AB  - BACKGROUND: Several angiotensin-converting enzyme inhibitors have
      antiproliferative effects in a rat model after carotid artery balloon injury.
      METHODS AND RESULTS: We conducted a randomized, double-blind, placebo-controlled
      trial to assess the effect of fosinopril, a novel angiotensin-converting enzyme
      inhibitor, in restenosis prevention after percutaneous transluminal coronary
      angioplasty (PTCA). Patients received fosinopril or matched placebo 10 mg at
      least 18 hours before PTCA, 20 mg at least 4 hours before PTCA, and 40 mg daily
      for 6 months. In addition, all patients received aspirin. Coronary angiograms
      before PTCA and immediately after PTCA as well as at 6-month follow-up were
      quantitatively analyzed. A total of 509 patients were recruited. The final per
      protocol population consisted of 153 fosinopril-treated and 151 placebo-treated
      patients. Restenosis rates according to the National Heart, Lung, and Blood
      Institute criterion 4 (loss of > or = 50% of the initial gain [primary end
      point]) were 45.7% and 40.7% in the fosinopril and control groups, respectively
      (not significant). The respective mean differences in minimal coronary luminal
      diameter between post-PTCA and follow-up angiograms were -0.59 +/- 0.71 mm and 
      0.51 +/- 0.67 mm (not significant). Clinical events during the 6-month follow-up
      period, analyzed on an on-treatment basis, were ranked according to the most
      serious event. The respective numbers in the fosinopril and the control groups
      were for death, 0 and 0; myocardial infarction, 0 and 0; coronary artery bypass
      graft surgery, 1 and 3; repeat PTCA, 35 and 35; recurrent signs of ischemia
      necessitating early repeat coronary angiography and managed medically, 6 and 7;
      and none of the above, 111 and 106. All these differences were significant.
      CONCLUSIONS: Administration of fosinopril in a dose of 40 mg daily during 6
      months after PTCA does not prevent restenosis and has no effect on overall
      clinical outcome.

PMID- 8281675
TI  - Increased vascular responsiveness to norepinephrine in rats with heart failure is
      endothelium dependent. Dissociation of basal and stimulated nitric oxide release.
AB  - BACKGROUND: Endothelial dysfunction and abnormal vascular responsiveness to
      vasoconstrictors may play an important role in chronic heart failure (CHF). The
      purpose of our study was to (1) evaluate whether the vascular response to
      norepinephrine is abnormal in a rat model of heart failure; (2) investigate the
      role of alpha 1- and alpha 2-adrenergic receptors; and (3) assess the
      contribution of the endothelium, and specifically endothelium-derived nitric
      oxide, to this response. METHODS AND RESULTS: Concentration-response curves of
      rat thoracic aortic rings were studied in isolated organ baths at 1 week after
      coronary artery ligation. In CHF rats, norepinephrine-induced contractions were
      increased in intact rings compared with rings from sham rats, despite decreased
      contraction in denuded rings. Decreased alpha 1-receptor sensitivity was
      demonstrated by the increased EC50 of methoxamine in endothelium-denuded rings
      from CHF rats, although maximal responses to KCl contraction were also decreased
      in CHF. There was no difference in the vascular response to clonidine, and
      acetylcholine-mediated relaxations were preserved in CHF rats, suggesting normal
      stimulated nitric oxide release. However, nitric oxide synthase inhibition with N
      omega-nitro-L-arginine methyl ester, as well as measurements of basal cGMP,
      demonstrated that basal nitric oxide release was decreased in CHF rats.
      CONCLUSIONS: This study demonstrates that the increased vascular responsiveness
      to norepinephrine in intact vessels from rats with heart failure is the result of
      decreased basal nitric oxide release and suggests that the dissociation of basal
      and stimulated nitric oxide release may play a pathophysiology role at an early
      stage of heart failure.

PMID- 8281676
TI  - Effect of endurance training early or late after coronary artery occlusion on
      left ventricular remodeling, hemodynamics, and survival in rats with chronic
      transmural myocardial infarction.
AB  - BACKGROUND: Remodeling of infarcted and noninfarcted ventricular regions, infarct
      expansion, shape distortion, and global left ventricular (LV) dilation influence
      LV performance and survival. The effect of chronic exercise, initiated early or
      later after infarction, on remodeling, hemodynamics, and survival has not been
      studied. METHODS AND RESULTS: A total of 156 rats were randomized after coronary
      artery occlusion or sham operation to remain sedentary or to start with swim
      training 4 days or 21 days after coronary occlusion, which was continued over 8
      weeks (6 days per week, 90 minutes per day). These intervals after coronary
      artery ligation were chosen because final size of infarction is well reached
      after 4 days; histological evolution of scar healing is still in progress, and
      after 21 days, histological scar healing is completed. At 8 weeks, hemodynamics
      were measured and LV dilation quantitated by passive pressure-volume curves. In
      groups with small (< or = 35%) and large (> 35%) infarcts, the area enclosed by
      endocardial circumference, infarct size, LV diameter, scar thickness, and septal
      thickness were measured in stained transverse serial LV sections to assess
      aneurysmal shape distortion and the response of infarcted and noninfarcted
      myocardia. Survival was not influenced by infarction or exercise alone. In rats
      with small infarcts, LV volume and shape and long-term survival were not altered
      by chronic exercise initiated early or late after coronary artery ligation.
      Mortality rose in animals with large infarction as a result of exercise (P <
      .0001) and was 47.6% with early exercise and 26.7% with late exercise (P < .05,
      early versus late). Infarct size in rats with early exercise (48 +/- 3%) was
      similar compared with infarct size of rats with late exercise (46 +/- 2%, P = NS
      compared with early exercise). Exercise did not affect LV dysfunction (assessed
      by systolic and end-diastolic pressures and dP/dtmax) in survivors of small and
      large infarctions. LV volumes increased (P < .05) in sedentary rats by large
      infarction (n = 13, 0.48 +/- 0.04 mL) compared with volumes after sham operation
      (n = 33, 0.33 +/- 0.03 mL) and with exercise (early, n = 11, 0.56 +/- 0.04 mL;
      late, n = 11, 0.65 +/- 0.04; P < .05 versus sedentary). In nonsurvivors from
      early exercise, the area enclosed by LV endocardial circumference (which
      corresponds to LV volume) was increased by 195%, LV diameter was increased by
      60%, and scar thickness was reduced by 37% (P < .05 versus respective control).
      Septal thickness increased in survivors by exercise (+25%) but decreased (-28.6%)
      in nonsurvivors (P < .0001 versus respective control). CONCLUSIONS: Endurance
      training in rats after small infarction, whether started early or late after left
      coronary artery ligation, was well tolerated without changes in LV volume, shape,
      hemodynamics, and long-term survival. Endurance training in rats with large
      infarction decreased overall survival (P < .0001). In survivors from late
      exercise, training caused aggravation of global LV dilation without additional
      shape changes. Endurance training after large infarction caused aggravation of
      remodeling to a degree that was not compatible with life in 27% of the rats with
      late exercise and in 48% with early exercise after coronary artery ligation,
      despite similar exercise. This was explained by extensive remodeling that was
      most pronounced in nonsurvivors from early exercise. In these rats, severe global
      LV dilation, distortion of LV shape, scar thinning, and a paradoxic reduction of
      septal thickness, ie, mismatch of infarcted and noninfarcted myocardia, were
      observed.

PMID- 8281677
TI  - Ventricular proarrhythmic effects of ventricular cycle length and shock strength
      in a sheep model of transvenous atrial defibrillation.
AB  - BACKGROUND: Synchronized cardioversion is generally accepted as safe for the
      treatment of ventricular tachycardia and atrial fibrillation when shocks are
      synchronized to the R wave and delivered transthoracically. However, others have
      shown that during attempted transvenous cardioversion of rapid ventricular
      tachycardia, ventricular fibrillation (VF) may be induced. It was our objective
      to evaluate conditions (short and irregular cycle lengths [CL]) under which VF
      might be induced during synchronized electrical conversion of atrial fibrillation
      with transvenous electrodes. METHODS AND RESULTS: In 16 sheep (weight, 62 +/- 7.8
      kg), atrial defibrillation thresholds (ADFT) were determined for a 3-ms/3-ms
      biphasic shock delivered between two catheters each having 6-cm coil electrodes,
      one in the great cardiac vein under the left atrial appendage and one in the
      right atrial appendage along the anterolateral atrioventricular groove. A
      hexapolar mapping catheter was positioned in the right ventricular apex for shock
      synchronization. In 8 sheep (group A), a shock intensity 20 V less than the ADFT
      was used for testing, and in the remaining 8 sheep (group B), a shock intensity
      of twice ADFT was used. With a modified extrastimulus technique, a basic train of
      eight stimuli alone (part 1) and with single (part 2) and double (part 3)
      extrastimuli were applied to right ventricular plunge electrodes. Atrial
      defibrillation shocks were delivered synchronized to the last depolarization. In
      part 4, shocks were delivered during atrial fibrillation. The preceding CL was
      evaluated over a range of 150 to 1000 milliseconds. Shocks were also delayed 2,
      20, 50, and 100 milliseconds after the last depolarization from the stimulus
      (parts 1 through 3) or intrinsic depolarization (part 4). The mean ADFT for group
      A was 127 +/- 48 V, 0.71 +/- 0.60 J and for group B, 136 +/- 37 V, 0.79 +/- 0.42
      J (NS, P > .15). Of 1870 shocks delivered, 11 episodes of VF were induced. Group
      A had no episodes of VF in part 1, two episodes of VF in part 2 (CL, 240 and 230
      milliseconds with 2-millisecond delay), and one episode each in parts 3 (CL, 280
      milliseconds with 2-millisecond delay) and 4 (CL, 240 milliseconds with 100
      millisecond delay). Group B had two episodes in part 1 (CL, 250 and 300
      milliseconds with 20-millisecond delay), three episodes in part 2 (CL, 230, 230,
      and 250 milliseconds with 2-millisecond delay), and one episode each in parts 3
      (CL, 260 milliseconds with 2-millisecond delay) and 4 (198 milliseconds with 100
      millisecond delay). No episodes of VF were induced for shocks delivered after a
      CL > 300 milliseconds. CONCLUSIONS: Synchronized transvenous atrial
      defibrillation shocks delivered on beats with a short preceding ventricular cycle
      length (< 300 milliseconds) are associated with a significantly increased risk of
      initiation of VF. To decrease the risk of ventricular proarrhythmia, short CLs
      should be avoided.

PMID- 8281678
TI  - History of drugs for thrombotic disease. Discovery, development, and directions
      for the future.
AB  - The history of the antithrombotic agents--aspirin, heparin, warfarin, and the
      thrombolytics--is a rich and lively odyssey of serendipity, perseverance, vision,
      and conflict involving a number of striking personalities. The history of aspirin
      spans ages and continents from Hippocrates' analgesic for women in labor to the
      rediscovery of the white willow bark by English country scholar Reverend Edward
      Stone. Bayer chemist Felix Hoffmann reinvented aspirin for his ailing father;
      suburban physician L.L. Craven pioneered the prophylactic antithrombotic uses of
      aspirin; and Sir John Vane elucidated aspirin's mechanism of action as the
      inhibition of prostaglandin synthetase. Heparin was discovered by McLean, working
      as a medical student in 1915 in search of a pure procoagulant in dog liver. His
      original impure material differed somewhat from today's heparin, but purified
      heparin was rapidly accepted for a myriad of clinical uses; to this day, diverse
      new properties of this complex glycosaminoglycan continue to be elucidated. The
      oral anticoagulants emerged from veterinary research in the 1920s on a
      hemorrhagic disorder afflicting cattle that consumed spoiled sweet clover hay.
      Several chance encounters led Karl Link and his University of Wisconsin team to
      the identification of dicumarol as the offending agent in 1939 and its widespread
      therapeutic use by Wright and others in the 1940s. Link later developed warfarin
      as a rodenticide, but its use in humans soon followed in the 1950s. Vitamin K was
      discovered in the 1930s; its involvement in the mechanism of the anticoagulant
      agents was not delineated until the 1970s. The intrinsic ability of clotted blood
      to liquify and the fibrinolytic properties of normal urine were noted in the
      1800s. Tillett and Sherry's group stumbled on the fibrinolytic properties of
      streptokinase in the 1930s and pioneered the therapeutic use of streptokinase in
      the 1940s and of urokinase in the 1960s. Several teams found tissue-type
      plasminogen activator in various body sites beginning in the 1940s, leading to
      its cloning and widespread use in the 1980s; anisoylated plasminogen
      streptokinase activator complex is an example of rational drug design. The
      discoverers of these diverse agents have not only provided physicians with a
      potent armamentarium of antithrombotic drugs but also helped elucidate much basic
      science and vividly demonstrated the merits of perseverance, independent thought,
      and adherance to the scientific method.

PMID- 8281679
TI  - Constrictor and dilator responses to intracoronary acetylcholine in adjacent
      segments of the same coronary artery in patients with coronary artery disease.
      Endothelial function revisited.
AB  - BACKGROUND: In patients with angiographically detectable atherosclerosis or in
      those with risk factors for coronary artery disease, intracoronary acetylcholine
      causes coronary constriction instead of endothelium-derived relaxing factor
      mediated dilation. Therefore, it has been hypothesized that diffuse endothelial
      dysfunction precedes development of coronary atherosclerosis. We tested this
      hypothesis in a systematic investigation of the effects of ascending doses of
      acetylcholine on the diameters of nonstenotic segments of the left coronary
      artery in patients with advanced atherosclerosis and coronary risk factors.
      METHODS AND RESULTS: Effects of intracoronary infusion of acetylcholine (10(-6)
      to 10(-4) mol/L) on diameters of proximal, middle, and distal nonstenotic
      segments of the left coronary artery were studied in 28 consecutive patients with
      chronic stable angina, positive exercise tests, and angiographic evidence of
      obstructive atherosclerosis (> or = 50% reduction in lumen diameter in at least
      one vessel). Two patterns of response to the maximal acetylcholine dose (10(-4)
      mol/L) were observed. In 21 patients (group 1), only constriction was observed in
      all left anterior descending and circumflex artery segments studied (16 +/- 3%,
      19 +/- 4%, and 23 +/- 4%, respectively; P < .01 compared with control). In 7
      other patients (group 2), both constriction and dilation were observed in
      adjacent segments of the same vessel; maximal acetylcholine dose caused
      constriction in 14 left anterior descending artery segments from a control
      diameter of 1.94 +/- 0.19 to 1.33 +/- 0.26 mm (37% reduction, P < .01) and
      dilation in 16 other segments from 1.63 +/- 0.22 to 1.93 +/- 0.21 mm (25%
      increase, P < .01). In the circumflex artery, this dose caused constriction in 16
      segments from a control diameter of 1.88 +/- 0.14 to 1.33 +/- 0.17 mm (31%
      reduction, P < .01) and dilation in 12 segments from 1.37 +/- 0.12 to 1.71 +/-
      0.09 mm (34% increase, P < .01). CONCLUSIONS: In 25% of patients studied with
      advanced angiographic coronary atherosclerosis and coronary risk factors,
      coronary segments with acetylcholine-inducible dilatation are present. In these
      patients, the endothelium is not diffusely dysfunctional as currently believed
      but rather shows marked segmental heterogeneity in the response to acetylcholine
      reflecting degrees of endothelial dysfunction.

PMID- 8281680
TI  - The impending crisis awaiting cardiac transplantation. Modeling a solution based
      on selection.
AB  - BACKGROUND: Each month, the number of transplant candidates added to the waiting
      list exceeds the number of transplantations performed, and many outpatients
      deteriorate to require transplantation urgently. The current list of 2400
      candidates and the average wait of 8 months continue to increase. METHODS AND
      RESULTS: To determine the size at which the outpatient and critical candidate
      pools will stabilize, population models were constructed using current statistics
      for donor hearts, candidate listing, sudden death, and outpatient decline to
      urgent status and revised to predict the impact of alterations in policies of
      candidate listing. If current practices continue, within 48 months the predicted
      list will stabilize as the sum of an estimated 270 hospitalized candidates, among
      whom, together with newly listed urgent candidates, all hearts will be
      distributed and 3700 outpatient candidates with virtually no chance of
      transplantation unless they deteriorate to an urgent status. Decreasing the upper
      age limit now to 55 years would reduce the number listed each month by 30% and
      result within 48 months in a list of only 1490. The list could also be decreased
      by 30%, however, if it were possible to list only a candidate group with an 80%
      chance (compared with 52% estimated currently) of sudden death or deterioration
      during the next year. With this strategy, the waiting list would equilibrate
      within 48 months to one-third the current size, with 50% of hearts for outpatient
      candidates, who would then have an 11% chance each month of receiving a heart
      compared with 0% if recent policies prevail. Total deaths, with and without
      transplantation, would be minimized by this rigorous selection of outpatient
      candidates. CONCLUSIONS: This study implies that immediate provisions should be
      made to limit candidate listing and revise expectations to reflect the
      diminishing likelihood of transplantation for outpatient candidates. Future
      emphasis should be on improved selection of candidates at highest risk without
      transplantation.

PMID- 8281681
TI  - Renin is not synthesized by cardiac and extrarenal vascular tissues. A review of
      experimental evidence.
AB  - A comprehensive review of physiological and molecular biological evidence refutes
      claims for synthesis of renin by cardiac and vascular tissues. Cardiovascular
      tissue renin completely disappears after binephrectomy. Residual putative
      reninlike activity, where investigated, has had the characteristics of lysosomal
      acid proteases. Occasional reports of renin or renin mRNA in vascular and cardiac
      tissues can be ascribed to failure to remove the kidneys 24 hours beforehand,
      overloading of detection systems, problems with stringency in identification, and
      illegitimate transcripts after more than 25 cycles of polymerase chain reaction.
      Others, using more stringent criteria, have failed to detect cardiac and vascular
      renin mRNA. Accordingly, a growing number of investigators have concluded that
      the kidneys are the only source of cardiovascular tissue renin. Although prorenin
      is secreted from extrarenal tissues as well as from the kidneys, there is no
      evidence that it is ever converted to renin in the circulation. The kidney is the
      only tissue with known capacity to convert prorenin to renin and to secrete
      active renin into the circulation. Accordingly, renin of renal origin determines
      plasma and hence, extracellular fluid renin levels. In these loci, angiotensin
      (Ang) I, formed by renin cleavage of circulating and interstitial fluid
      angiotensinogen, is in turn cleaved by angiotensin converting enzyme, located in
      plasma and extracellular fluids and on the luminal surface of pulmonary and
      systemic vascular endothelial cells, to Ang II, which perfuses and bathes the
      heart and vasculature. Consistent with this model, plasma renin and angiotensin
      and the antihypertensive action of renin inhibitors, converting enzyme inhibitor,
      or Ang II antagonists all disappear after binephrectomy. Thus, the plasma renin
      level, via Ang II formation, determines renin system vasoconstrictor activity,
      the antihypertensive potential of anti-renin system drugs, and the risk of heart
      attack in hypertensive patients. This analysis redirects renin research to renal
      mechanisms that create the plasma renin level, to renal prorenin biosynthesis and
      its processing to renin, and to their regulated secretion, extracellular
      distribution, and possible binding to by target tissues. In this context, it is
      still possible that changes in circulating and interstitial renin substrate or
      available converting enzyme might exert subtle modulating influences on Ang II
      formation. However, this analysis redefines the importance of plasma renin
      measurements to assess clinical situations, because plasma renin is the only
      known initiator driving the cardiovascular renin-angiotensin system, and its
      strength can be measured.

PMID- 8281682
TI  - Evaluating new devices. Acute (in-hospital) results from the New Approaches to
      Coronary Intervention Registry.
AB  - BACKGROUND: To be used optimally, new interventional devices (stent, lasers,
      atherectomy catheters) must be carefully evaluated in terms of optimal patient
      and lesion selection, technique of use, expected acute success and complications,
      and long-term results. Sources for that information include single-center and
      multicenter (single-device) reports, although randomized trials may then be
      performed to provide a more definitive picture of any clinical benefits. One
      interim option, however, consists of carefully collected registry data. The
      purpose of this article is to review data collected in the National Heart, Lung,
      and Blood Institute-funded New Approaches to Coronary Intervention (NACI)
      Registry and to compare them with existing reports. METHODS AND RESULTS: NACI is
      an independent, investigator-driven effort that seeks to collect uniform data on
      patients undergoing treatment with one of several investigational devices and
      thereby provide an unbiased report of procedure outcome. Between November 1990
      and November 1992, 36 participating centers treated a total of 3201 lesions in
      2835 patients, using one of seven study devices: directional atherectomy (1084
      lesions), transluminal extraction atherectomy (240 lesions), rotational
      atherectomy (349 lesions), Palmaz-Schatz stent (674 lesions), Gianturco-Roubin
      stent (213 lesions), and the Advanced Interventional Systems (474 lesions) or
      Spectranetics (167 lesions) excimer lasers. Data on each procedure were recorded
      on a unique modular database that captured the reason for (and interim result
      after) each device use. Device success (defined here as stenosis improvement by >
      or = 20% and a residual stenosis < 50% after new device use) was 66.5% overall.
      Adjunctive angioplasty was used in 75.5% of lesions, either before (25.9%) or
      after (43.5%) new device use, yielding an overall lesion success (> or = 20%
      stenosis improvement with a final residual stenosis < 50% after all devices) of
      92.2%. Adjunctive angioplasty after new device use produced further enlargement
      in minimal lumen diameter (from 2.2 to 2.7 mm) and further reduction in residual
      stenosis (26.4% to 16.1%) compared with the results present after use of the new
      devices themselves. Major complications consisting of death (1.6%), Q-wave
      myocardial infarction (1.3%), or emergency bypass surgery (1.7%) occurred in 4.0%
      of patients (range, 2.6% to 8.7% across devices). Procedural success, defined as
      lesion success in all new device-treated lesions without a major complication,
      was achieved in 90.8% of patients, with a median length of hospital stay of 4
      days. CONCLUSIONS: NACI illustrates the type of information that can be obtained
      in a registry format that examines the acute angiographic and clinical results of
      new devices according to uniform definitions. Although no registry can substitute
      for formal interdevice trials, registries such as this can supplement earlier
      single-center and multicenter reports. In doing so, they can help focus
      subsequent randomized interdevice comparisons on lesion types for which two or
      more devices have promising acute results. Given the substantial interdevice
      differences in baseline patient and lesion characteristics found in NACI, simple
      "head-to-head" comparison of the results of different devices might give
      misleading impressions and should be avoided unless such comparisons are
      restricted to carefully matched patient and lesion subgroups.

PMID- 8281683
TI  - Images in cardiovascular medicine. Untreated gangrene in patients with peripheral
      artery disease.

PMID- 8281684
TI  - A middle-aged woman with dyspnea, cachexia, increased abdominal girth,
      pericardial effusion, and a continuous murmur.

PMID- 8281685
TI  - Tissue angiotensin system in cardiovascular medicine. A paradigm shift?

PMID- 8281686
TI  - Molecular genetics. Therapy or terror?

PMID- 8281687
TI  - Role of inflammation in coronary plaque disruption.

PMID- 8281689
TI  - Long QT syndrome in children.

PMID- 8281688
TI  - Survival after congestive heart failure in Framingham Heart Study subjects.

PMID- 8281690
TI  - Sinus node during atrial fibrillation.

PMID- 8281691
TI  - Coronary angioplasty practice in the United States.

PMID- 8281692
TI  - Guidelines for peripheral percutaneous transluminal angioplasty of the abdominal
      aorta and lower extremity vessels. A statement for health professionals from a
      special writing group of the Councils on Cardiovascular Radiology,
      Arteriosclerosis, Cardio-Thoracic and Vascular Surgery, Clinical Cardiology, and
      Epidemiology and Prevention, the American Heart Association.

PMID- 8281693
TI  - Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to
      acetylcholine in postmenopausal women.
AB  - BACKGROUND: Estrogen administration in postmenopausal women is associated with a
      50% reduction in the clinical manifestations of coronary artery disease. The
      mechanisms are not known, although one potential explanation is estrogen-induced
      modulation of coronary vasoreactivity. Acetylcholine is an endothelium-dependent
      vasodilator that may be used to assess coronary vasoreactivity and elicits
      coronary responses that parallel those found with common daily vasomotor stimuli.
      Therefore, we tested whether estrogen attenuates abnormal coronary vasomotor
      responses to acetylcholine in postmenopausal women. METHODS AND RESULTS:
      Acetylcholine-induced changes in coronary flow, resistance, and cross-sectional
      area were determined before and 15 minutes after intravenous administration of
      ethinyl estradiol (EE, 35 micrograms) in 15 postmenopausal women. The influence
      of estrogen on basal coronary flow, resistance, and epicardial cross-sectional
      area was also assessed by measuring these parameters before and after EE or
      placebo administration in 33 women. Estrogen altered basal coronary vasomotor
      tone in 22 women as manifested by an EE-induced 23.3 +/- 4.5% (mean +/- SEM)
      increase (P < .01) in coronary flow, a 15.0 +/- 3.2% decrease (P < .01) in
      resistance, and a 20.0 +/- 6.5% increase (P = .02) in epicardial cross-sectional
      area. Placebo administration in 11 women did not change these parameters.
      Estrogen also attenuated abnormal coronary vasomotor responses to acetylcholine.
      Seven women who exhibited a paradoxical acetylcholine-induced decrease in
      coronary flow (-33.5 +/- 12.3%, P < .01) and increase in resistance (38.9 +/-
      14.1%, P = .05) and seven who had an abnormal acetylcholine-induced decrease in
      epicardial cross-sectional area (-14.2 +/- 4.4%; P = .04) did not have
      acetylcholine-induced changes in these parameters after EE administration.
      Acetylcholine-induced flow, resistance, and cross-sectional area responses before
      and after EE were significantly different (P < .01, P = .02, and P = .02,
      respectively). Normal coronary responses to acetylcholine were not affected by EE
      administration. CONCLUSIONS: EE attenuates abnormal coronary vasomotor responses
      to acetylcholine in postmenopausal women. EE also decreases basal coronary
      vasomotor tone as manifested by increased coronary flow, decreased resistance,
      and increased epicardial cross-sectional area. These acute effects of estrogen on
      coronary vasoreactivity may explain, in part, the cardioprotective effects of
      estrogen in postmenopausal women.

PMID- 8281694
TI  - Report of the Task Force on Vascular Medicine.

PMID- 8281695
TI  - Access to health care: issues and principles. President's address to the 66th
      scientific sessions of the American Heart Association. November 8, 1993. Georgia
      World Congress Center, Atlanta, Georgia.

PMID- 8281696
TI  - Long-term prognostic importance of patency of the infarct-related coronary artery
      after thrombolytic therapy for acute myocardial infarction.
AB  - BACKGROUND: After thrombolytic therapy, long-term patency of the infarct-related
      artery may reduce arrhythmias, limit ventricular dilatation, and provide
      collaterals to another infarct zone if further infarction occurs. However,
      independent long-term prognostic value of infarct artery patency has not been
      shown. METHODS AND RESULTS: We followed 312 patients with first myocardial
      infarction treated < 4 hours after pain onset with thrombolysis (streptokinase [n
      = 188] or recombinant tissue-type plasminogen activator [n = 124]). At 28 +/- 11
      days, cardiac catheterization was performed. Flow of the infarct-related artery
      was assessed by the TIMI scoring system, and a scoring system relating coronary
      stenoses and flow to the amount of myocardium supplied was also used. Follow-up
      was for 39 +/- 13 months. Cardiac death occurred in 5.8% of patients, and there
      were two noncardiac deaths. Revascularization was performed in 11.5% of patients.
      On univariate and multivariate analysis, ventricular function (ejection fraction,
      P = .006 and .02, or end-systolic volume index, P = .01 and .06) was the most
      important prognostic factor. Patency of the infarct-related artery measured as
      TIMI 3 flow was marginally significant on univariate analysis (P = .08) but not
      on multivariate analysis (P = .2). Patency was an independent prognostic factor
      in univariate and multivariate analysis when measured as an occlusion score
      (amount of myocardium supplied by an occluded artery, P = .01 and < .05). When
      the ejection fraction was > or = 50%, only occluded arteries supplying > 25% of
      the left ventricle affected prognosis adversely. If the ejection fraction was <
      50%, occluded arteries supplying < 25% of myocardium also adversely affected
      prognosis. Treadmill exercise duration 4 weeks after infarction was the only
      other prognostic factor identified. CONCLUSIONS: Ventricular function and infarct
      related artery patency are independent prognostic factors after thrombolytic
      therapy for acute myocardial infarction.

PMID- 8281697
TI  - Quantitative two-dimensional echocardiographic measurements are major predictors
      of adverse cardiovascular events after acute myocardial infarction. The
      protective effects of captopril.
AB  - BACKGROUND: Left ventricular enlargement after myocardial infarction increases
      the likelihood of an adverse outcome. In an echocardiographic substudy of the
      Survival and Ventricular Enlargement (SAVE) Trial, we assessed whether captopril
      would attenuate progressive left ventricular enlargement in patients with left
      ventricular dysfunction after acute myocardial infarction and, if so, whether
      this would be associated with improved clinical outcome. METHODS AND RESULTS: Two
      dimensional transthoracic echocardiograms were obtained in 512 patients at a mean
      of 11.1 +/- 3.2 days after infarction and were repeated at 1 year in 420
      survivors. Left ventricular size was assessed as left ventricular cavity areas at
      end diastole and end systole and left ventricular function as percent change in
      cavity area from end diastole to end systole. Patients were randomly assigned to
      placebo or captopril, and the incidence of adverse cardiovascular events
      consisting of cardiovascular death, heart failure requiring either
      hospitalization or open-label angiotensin-converting enzyme inhibitor therapy,
      and recurrent infarction were determined over a follow-up period averaging 3.0 +/
      0.6 years. Irrespective of treatment assignment, baseline left ventricular
      systolic area and percent change in area were strong predictors of cardiovascular
      mortality and adverse cardiovascular events. At 1 year, left ventricular end
      diastolic and end-systolic areas were larger in the placebo than in the captopril
      group (P = .038, P = .015, respectively), and percent change in cavity area was
      greater in the captopril group (P = .005). One hundred eleven of the 420 1-year
      survivors with 1-year echo measurements (26.4%) experienced a major adverse
      cardiovascular event, and these patients had more than a threefold greater
      increase in left ventricular cavity areas than those with an uncomplicated
      course. Sixty-nine patients with adverse cardiovascular events were in the
      placebo group compared with 42 patients in the captopril-treated group (a risk
      reduction of 35%, P = .010). CONCLUSIONS: Two-dimensional echocardiography
      provides important and independent prognostic information in patients after
      infarction. Left ventricular enlargement and function after infarction are
      associated with the development of adverse cardiac events. Attenuation of
      ventricular enlargement with captopril in these patients was associated with a
      reduction in adverse events. This study demonstrates the linkage between
      attenuation of left ventricular enlargement by captopril after infarction and
      improved clinical outcome.

PMID- 8281698
TI  - Combination antithrombotic therapy in unstable rest angina and non-Q-wave
      infarction in nonprior aspirin users. Primary end points analysis from the ATACS
      trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.
AB  - BACKGROUND: The purpose of this study was to compare combination antithrombotic
      therapy with aspirin plus anticoagulation versus aspirin alone, when added to
      conventional antianginal therapy in patients with unstable rest angina or non-Q
      wave myocardial infarction who were nonprior aspirin users. METHODS AND RESULTS:
      Two hundred fourteen patients were randomized; 109 were randomized to receive
      aspirin alone (162.5 mg daily) and 105 to receive a combination of aspirin plus
      anticoagulation, ie, aspirin 162.5 mg daily plus heparin (activated partial
      thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus
      warfarin (international normalized ratio, 2 to 3). Trial therapy was begun by 9.5
      +/- 8.8 hours of qualifying pain and was continued for 12 weeks. Primary end
      points were recurrent angina with ECG changes, myocardial infarction, and/or
      death. Analysis by intention to treat of primary events at 12 weeks was
      performed. At 14 days, there was a significant reduction in total ischemic events
      in the combination group versus aspirin alone (10.5% versus 27%, P = .004). An
      efficacy analysis of primary events at 12 weeks also revealed a large reduction
      in total ischemic events in the combination group versus aspirin alone (13%
      versus 25%, P = .06). Bleeding complications were slightly more common with
      combination therapy. CONCLUSIONS: In nonprior aspirin users, combination
      antithrombotic therapy with aspirin plus anticoagulation significantly reduces
      recurrent ischemic events in the early phase of unstable angina.

PMID- 8281699
TI  - Evidence for an association between dehydroepiandrosterone sulfate and nonfatal,
      premature myocardial infarction in males.
AB  - BACKGROUND: Several studies indicate that endogenous hormones play a role in the
      etiology of coronary artery disease, either as independent risk factors or
      indirectly, via an effect on lipids, lipoproteins, or other heart disease risk
      factors. METHODS AND RESULTS: The relation between endogenous hormone levels and
      premature (< 56-year-old patients) myocardial infarction was assessed in a
      retrospective study involving 49 male survivors of premature myocardial
      infarction and 49 age-matched, volunteer male controls. Serum samples were
      obtained for each subject the morning after a > or = 12-hour fast and frozen at 
      70 degrees C for subsequent hormonal analysis. Among the male patients, the
      average duration between the most recent myocardial infarction and blood sampling
      was 3.4 years (range, 0.7 to 19.2 years). Individuals reporting the use of any
      medications with the potential to alter lipid, lipoprotein, or hormone levels
      were excluded from these analyses. Dehydroepiandrosterone sulfate levels were
      significantly lower in the patients than in the control subjects. This
      association remained statistically significant even after accounting for the
      effects of total cholesterol, triglycerides, the ratio of total to high-density
      lipoprotein (HDL) cholesterol, HDL, apolipoprotein A-I, apolipoprotein A-II,
      apolipoprotein B, and body mass index. There were no significant differences in
      the levels of estradiol, testosterone, or free testosterone or the ratio of
      estradiol to testosterone between patients and control subjects. CONCLUSIONS: Our
      conclusions are limited by the retrospective nature of this study. However, these
      data indicate that serum dehydroepiandrosterone sulfate levels are inversely
      related to premature myocardial infarction in males and that this association is
      independent of the effects of several known risk factors for premature myocardial
      infarction.

PMID- 8281700
TI  - Trans-fatty acids intake and risk of myocardial infarction.
AB  - BACKGROUND: Concern that trans-fatty acids formed in the partial hydrogenation of
      vegetable oils may increase the risk of coronary disease has existed for several
      decades, but direct evidence on this relation in humans is limited. METHODS AND
      RESULTS: With a case-control design, we studied the association between intake of
      trans-fatty acids and a first acute myocardial infarction among 239 patients
      admitted to one of six hospitals in the Boston area and 282 population control
      subjects. Intake of trans-fatty acids was estimated using a previously validated
      food frequency questionnaire. After adjustment for age, sex, and energy intake,
      intake of trans-fatty acids was directly related to risk of myocardial infarction
      (relative risk for highest compared with lowest quintile, 2.44; 95% confidence
      interval, 1.42, 4.19; for trend P < .0001). This relation remained highly
      significant after adjustment for established coronary risk factors, multivitamin
      use, and intake of saturated fat, monounsaturated fat, linoleic acid, dietary
      cholesterol, vitamins E and C, carotene, and fiber. Intake of margarine--the
      major source of trans-isomers--was significantly associated with risk of
      myocardial infarction. CONCLUSIONS: These data support the hypothesis that intake
      of partially hydrogenated vegetable oils may contribute to the risk of myocardial
      infarction.

PMID- 8281701
TI  - The effect of 17 beta-estradiol and endothelin 1 on prostacyclin and thromboxane
      production in human endothelial cell cultures.
AB  - The effect was investigated of endothelin 1 and 17 beta-estradiol on prostacyclin
      and thromboxane A2 production (determined as the stable metabolites 6-keto-PGF1
      alpha and thromboxane B2, respectively) in endothelial cell cultures obtained
      from veins of human umbilical cord. There was a statistically significant
      increase of 6-keto-PGF1 alpha production with endothelin 1 at concentrations of
      10(-8) and 10(-9) M [9.5 +/- 1.1% and 7.2 +/- 0.9%, (mean +/- SD, n = 5),
      respectively] compared to basal production. In contrast, 17 beta-estradiol alone
      (10(-6) and 10(-8) M) had no effect. In the presence of 17 beta-estradiol (10(-8)
      M) the stimulating effect of endothelin 1 (10(-8) and 10(-9) M) on 6-keto-PGF1
      alpha production was further enhanced to 60.0 +/- 22.5% and 39.5 +/- 22.1%,
      respectively, compared to basal values. With respect to thromboxane B2, no change
      in its production was observed by the addition of endothelin 1 and 17 beta
      estradiol, alone or in combination in the concentrations mentioned above. These
      results indicate that 17 beta-estradiol potentiates the effects of endothelin 1
      on prostacyclin production in human endothelial cells.

PMID- 8281702
TI  - Cultured human trophoblast cells reproduce the initial events of placental
      biology.
AB  - OBJECTIVE: The objective of this study was to determine whether cultured
      trophoblast cells shared the same morphological and biological properties
      observed in trophoblast, in vivo. STUDY DESIGN: Trophoblast cells from human term
      placenta were cultured, morphologically, biochemically and immunochemically
      monitored for as long as 30 days. RESULTS: Single cells progressively aggregated
      and fused into a syncytio, the Ca2+ and the Ca(2+)-ATPase activity drooped, and
      the 72 kDa collagenase (MMP-2) was consistently expressed. CONCLUSIONS: Term
      placenta trophoblast cultures can be viewed and used as a model system mimicking
      morphological and biochemical events of placenta biology and differentiation.

PMID- 8281703
TI  - Programmed oocyte retrieval.
AB  - Several methods of facilitating the work schedule for in vitro fertilization
      programs have been proposed. LH-RH agonists offer the possibility of manipulating
      the day of hCG injection and consequently the day of ovum pick-up. Moreover,
      after desensitization, follicles are contemporarily stimulated and a higher
      number of mature oocytes are retrieved. The same objective of follicle
      synchronization can be obtained with progestins, which have the advantage of
      minor cost and less adverse effects. The use of oral contraceptives offers
      similar results to those obtained with progestins. The best choice in work
      programming appears to be a "monitorized programmed oocyte retrieval" with the
      use of progestins and LH-RH agonists.

PMID- 8281704
TI  - A rabbit model for the evaluation of minimal access treatment of ectopic
      pregnancy in humans, using intrachorionic injection and local hyperthermia.
AB  - Rabbits at mid pregnancy were used as experimental models for investigating the
      feasibility of intrachorionic injection therapy in human ectopic pregnancy. Also,
      exposure of rabbit pregnancy to hyperthermia of 45 degrees C was studied. The
      experiments were followed by serial serum progesterone levels and by light as
      well as electron microscopy. Intrachorionic injection of different drugs led to
      demise in 92% of gestations. Application of hyperthermia to the pregnant rabbit
      uterus led in 94% to demise of gestations. Impairment of the reproductive
      functions after exposure did not occur. Injection was more effective up to day 15
      of pregnancy, while hyperthermia had better results in older gestations.
      Morphological reactions to injection of different drugs and to hyperthermia were
      similar. Irreversible damage to the uterine wall was not observed. Intrachorionic
      injection of drugs may be a suitable treatment of human ectopic pregnancy.
      Application of hyperthermia may be a promising future therapy.

PMID- 8281705
TI  - Microcolposcopy vs colposcopy in evaluating abnormal Pap smear. Comparison with
      histological findings.
AB  - Microcolposcopy is a microscopic examination which permits the observation of in
      vivo normal and dysplastic cells. A comparison was made between colposcopy and
      microcolposcopy in terms of sensitivity, specificity and predictive value in the
      diagnosis of cervical intraepithelial neoplasia. Seventy-eight patients with
      abnormal cervical smears were submitted to colposcopy, microcolposcopy and one or
      more biopsies on the microcolposcopically suspected areas. Currents
      classifications were used for the colposcopy and microcolposcopy. A comparison
      was made between the colposcopic description of abnormal transformation zone, and
      the microcolposcopic grade 2. The findings suggests that microcolposcopy is more
      sensitive and has more diagnostic accuracy than colposcopy in the diagnosis of
      cervical intraepithelial neoplasia. Microcolposcopy is a good alternative to
      colposcopy in evaluating abnormal cervical cytology.

PMID- 8281706
TI  - Color Doppler ultrasound in prenatal diagnosis of umbilical cord angiomyxoma.
      Case report.
AB  - A pregnant woman, at 28 weeks' gestation, has been observed ultrasonographically.
      A complex mass arising from the umbilical cord was detected. Color Doppler
      imaging demonstrated the vascular nature of the mass and the strictly connection
      with the three umbilical vessels. Color Doppler ultrasound provides useful
      informations for a correct assessment of the masses arising from the umbilical
      cord.

PMID- 8281707
TI  - Endocrine changes and follicular development in patients during ovulation
      induction using Goserelin and different gonadotropin treatments.
AB  - The aim of this study was to compare endocrine changes and the follicular
      development in patients receiving pure FSH alone or in association with LH after
      desensitization with an LH-RH agonist depot. Thirty four cycles were selected for
      this prospective randomized study. Desensitization was obtained using Goserelin
      the cycle before the stimulation. Induction of ovulation for IUI was carried out
      with 225 IU/day of pure FSH or with 225 IU/day of hMG. The number of days and
      ampules required for follicular maturation were equivalent in the two groups. The
      same number of follicles were developed, while different, but not significant,
      pregnancy rates were obtained. Estradiol values at the end of stimulation were
      significantly lower for FSH group. In conclusion the contemporary administration
      of LH with FSH does not exert any effect on follicular development, but it seems
      to facilitate E2 synthesis, probably providing more substrate for the
      aromatization process.

PMID- 8281708
TI  - Cystic adenomatoid malformation of fetal lung. Case report.

PMID- 8281709
TI  - Hypothesis for endometrial carcinoma carcinogenesis. Preventive prospects.
AB  - Considering endometrial carcinoma as a natural experimental model for in vivo
      study of carcinogenesis, a hypothesis of endometrial type A carcinogenesis and
      some preventive prospects are advanced. Under the name of endometrial carcinoma
      two different types are considered: A) hormone dependent type, and B) autonomous
      type. Aging, obesity, hypertension and/or diabetes, persistent exposure to
      unopposed exogenous or endogenous estrogens are recognized epidemiological
      factors for endometrial carcinoma. Experimental and clinical studies have shown
      that in pregnancy associated with clinical conditions characterized by a
      compromised maternal circulation in the intervillous space, a state of true or
      relative hypoxia stimulates syncytial hyperplasia, as adaptive process, in order
      to increase the exchange area of the placenta. Vaginosonographic studies have
      shown in patients with endometrial thickness greater than or equal to 4 mm
      complex and atypical hyperplasia than endometrial carcinoma in a higher
      percentage than in patients with endometrial thickness less than 3 mm. It seems
      that hypoxia in endometrial thickness, greater than 3 mm promoted by estrogens,
      would be a supplementary proliferating factor. Immunological studies have shown,
      in patients with complex or atypical hyperplasia of the endometrium and/or
      endometrial carcinoma, a host immunological reaction (DTHS-reactivity test) to a
      pharmaceutical placental suspension, when injected intradermally. An extract
      prepared from placental suspension is also recognized in vitro, by patients'
      serum (Ouchterlony's technique). To conclude, hypoxic insult, as common
      pathophysiological factor in most predisposing diseases for endometrial cancer,
      leads to a persistent multicellular hyperplasia of the endometrium. Sometimes
      populations with an altered growth pattern develop.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8281710
TI  - Chlamydia trachomatis diagnosis: a correlative study of pap smear and direct
      immunofluorescence.
AB  - From June 1989 to September 1990, 255 women with recurrent vaginitis, were
      evaluated, at the "Service of Precocious Diagnosis and Therapy of Gynecological
      Tumor" of the 1st Department of Obstetrics and Gynecology. They were compared
      with a control group of 255 women selected in the same time. All patients between
      the ages of 18-40 years, with normal sexual behaviour, had a negative colposcopy
      for HPV and HSV2 infections. The cervical smear with Papanicolaou technique and
      direct immunofluorescence (DIF) was performed in all patients. The specimens were
      examined with a fluorescence microscope (Leitz). Positive determinations were
      confined by examination a tha magnification of 600 X. Slides were scored as
      positive if at least 5 distinct apple-green fluorescence-stained elementary body
      per field was observed. The two groups were entirely comparable in age, parity,
      method of contraception, and number of sexual contacts over the preceding three
      months. Our data confirmed a higher incidence of Chlamydial infections in women
      with recurrent vaginitis (34.1%) than in control group (8.23%). In symptomatic
      women, more cases of metaplastic cells with cytoplasmic vacuolation, less
      inflammatory alteration and a lack of specific agents like CA and TV, were found
      than in the control group. The DIF positivity, in both groups, was connected with
      a cytological findings of metaplastic cells with cytoplasmic vacuolation in 72.3%
      and 50% respectively.

PMID- 8281711
TI  - Serum and cytosolic levels of CA549 in breast cancer patients.
AB  - CA 549 is a new mucinous circulating tumor marker recognized by two monoclonal
      antibodies (BC4E549 and BC4N154) recently proposed for breast cancer. In this
      report we compared the levels of CA 549 and CA 15.3, the best known biomarker for
      breast cancer nowadays, in 68 sieric and 59 cytosolic samples. Serum samples came
      from 59 breast patients (24 with primary disease = M-, 18 with systemic disease =
      M+, 17 with no evidence of disease after surgery = NED) and 9 women with benign
      breast disease = BBD. The cytosols were prepared from primary breast carcinomas
      according to the method used for hormonal receptors. At first we evaluated the
      analytical performance of the immunoradiometric assay for CA 549 (Hybri-BREScan,
      Hybritech) and its applicability to the cytosolic determination. Using a cut-off
      value of 12 U/mL for CA 549 and 28 U/mL for CA 15.3 serum levels, we obtained the
      following percentages of positivities: M- = 21%; M+ = 83%; NED = 0%; BBD = 22%
      for CA 549 and M- = 33%; M+ = 89%; NED = 18%; BBD = 22% for CA 15.3. CA 549 gave
      information concordant with CA 15.3 in a high percentage of cases both in sera
      and in cytosols, but the clinical relevance of cytosolic determination remains to
      be investigated. Since serum CA 549 showed an adequate sensitivity in M+ patients
      only, it may be proposed in the follow-up to confirm CA 15.3 abnormal values or
      as an alternative to it.

PMID- 8281712
TI  - Goserelin treatment in glandular hyperplasia.
AB  - Glandular Hyperplasia is commonly associated with meno and/or metrorrhagia. We
      treated 84 patients suffering from meno and/or metrorrhagia associated with
      simple glandular hyperplasia with a gonadotropin releasing hormone agonist,
      goserelin, (Zoladex, ICI Pharmaceuticals, Macclesfield. Cheshire, England),
      available in a depot formulation. Subcutaneous administration of goserelin 3.6 mg
      was repeated every 28 days for 6 months. Within the first 4 weeks from the start
      of therapy 45% of the patients became amenorrhoeic, within 12 weeks 100%. Only 3
      patients reported continued spotting. Hysteroscopic evaluation and biopsy have
      shown in the 84 evaluable patients, a positive result in 76 (90.4%),
      demonstrating the validity of the use of this analogue in this indication. In the
      future it would be of value to increase the period of treatment in selected cases
      as well as increasing the length of the follow-up period.

PMID- 8281713
TI  - Anti-GBM disease: predictive value of clinical, histological and serological
      data.
AB  - Twenty-nine patients with anti-glomerular basement membrane (GBM) disease,
      defined by circulating anti-GBM antibodies and/or linear deposits of
      immunoglobulin G along GBM, were studied retrospectively to identify prognostic
      indicators of renal outcome and pulmonary involvement. Patients consisted of 18
      males and 11 females aged 6 to 76 years (mean 35.2 +/- 20.2). Goodpasture
      syndrome developed in 14, disease was confined to renal manifestations in 14 and
      isolated pulmonary involvement was present in a single case. Pulmonary disease
      was significantly associated with current smoking (p < 0.01). Among the 29
      patients, end-stage renal failure requiring dialysis was initially observed in 16
      (55%). Ten of them had anti-GBM glomerulonephritis (GN) and 4 presented with
      Goodpasture syndrome; the two other patients died very soon after the beginning
      of the disease. The 17 patients with an unfavourable renal evolution (group 1)
      and the 12 patients with favourable evolution or chronic renal failure (group 2)
      were compared. No significant difference was noted between the two groups
      concerning the age at onset of the disease, sex, cigarette smoking or pulmonary
      involvement. Conversely, creatininemia over 600 mumol/l, oligoanuria, absence of
      normal glomeruli, a high percentage of circumferential crescents, circulating
      anti-GBM antibodies detected by immunofluorescence, and a high level of
      circulating anti-GBM antibodies evaluated by ELISA were features which indicate
      an unfavourable renal course (p < 0.01).

PMID- 8281714
TI  - Serum myeloperoxidase and serum cytokines in anti-myeloperoxidase antibody
      associated glomerulonephritis.
AB  - Anti-MPO antibodies, serum MPO and cytokines were examined in 106 patients with
      glomerulonephritis. Twenty-three patients had anti-MPO antibodies and crescent
      formation; 17 had crescentic glomerulonephritis (CRGN) and the remaining 6 had
      focal segmental necrosis with less than 50% crescent formation in the observed
      glomeruli. Pauci-immune CRGN accounted for 28 of 43 CRGN cases. Anti-MPO antibody
      titers were significantly higher in the cellular crescent stage and their titers
      correlated well with the number of crescents. Clinical observation revealed that
      11 of 18 patients with anti-MPO antibody-associated CRGN had a respiratory tract
      infection prior to the onset of overt glomerulonephritis. Serum MPO was detected
      in 20 of 23 patients with anti-MPO antibodies and the amounts of MPO were
      especially high in the cellular crescent stage and correlated with anti-MPO
      antibodies. TNF-alpha and IL-6 were also detected in the sera in parallel with
      the anti-MPO antibody titers. These data suggest that anti-MPO antibodies, TNF
      alpha and IL-6, induced by the infection, may activate neutrophils and MPO itself
      released from neutrophils, may play an important pathogenetic role in glomerular
      capillary necrosis leading to CRGN.

PMID- 8281715
TI  - ANCA associated vasculitis allergica cutis (VAC) and mild proliferative
      necrotizing glomerulonephritis.
AB  - We report here the case of a 69-year-old male with vasculitis allergica cutis
      (VAC) accompanied by a nephrotic syndrome associated with serum perinuclear
      staining anti-neutrophil cytoplasmic antibody (P-ANCA). Renal biopsy specimens
      showed mild proliferative glomerulonephritis with crescentic and necrotizing
      lesion in the glomeruli, while lesional skin biopsy specimens showed
      leukocytoclastic vasculitis in the deep dermis. Pauci-immune deposits were
      evident (deposits of immunoglobulins and complements were absent) by
      immunofluorescence microscopy in both tissues. The appearance of weakly positive
      P-ANCA associated with skin lesions and renal dysfunction occurred twice in this
      patient. Following corticosteroid administration, renal dysfunction was
      remarkably diminished and proteinuria decreased. P-ANCA titer were decreased,
      reaching the normal level. ANCA associated glomerulonephritis complicated by VAC
      has not been reported previously. In the present case, the vasculitis cutis and
      glomerulonephritis is assumed to be associated with the appearance of weakly
      positive P-ANCA.

PMID- 8281716
TI  - Interpatient variation in response to subcutaneous versus intravenous low dose
      erythropoietin.
AB  - Subcutaneous (SC) recombinant human erythropoietin (EPO) has been reported to
      correct anemia in hemodialysis patients at lower doses than intravenous (IV) EPO.
      Those trials involved relatively high doses of EPO or did not control adequately
      for time-related falls in dose requirements. Therefore, on open-label double
      crossover study was performed to compare the hemoglobin (Hb) response to low dose
      SC versus IV EPO. Ten (4 male) maintenance hemodialysis patients previously
      stabilised on low dose EPO for 18 +/- 3 months (mean +/- SEM) were given EPO IV
      for 12 weeks (IV#1), then SC for 24 weeks and then IV for a further 20 weeks
      (IV#2). Iron status and other factors known to modify response to EPO were kept
      constant. EPO dose was not changed unless Hb rose above 100 g/l, when the dose
      was reduced to keep Hb between 90 and 100 g/l. Initial EPO dose was 64 +/- 10
      u/kg/week. Mean Hb, measured monthly, was not different during the 3 treatment
      periods. There was wide interpatient variation in the relative response to IV
      versus SC EPO. Mean Hb was higher on IV EPO in 5 patients (by 6.1 +/- 2.0 g/l)
      and higher on SC EPO in 5 patients (by 12.1 +/- 4.1 g/l). The difference in mean
      Hb during IV versus SC administration was more than 5 g/l in 6 patients, being
      higher in 3 patients during IV administration (by 8.7 +/- 4.6 g/l) and in 3
      during SC (by 17.4 +/- 4.6 g/l). In conclusion, the more efficient route of
      administration of EPO is not predictable for individual patients, and should be
      sought to allow possible dose reduction.

PMID- 8281718
TI  - Diffusion kinetics of urea, creatinine and uric acid in blood during
      hemodialysis. Clinical implications.
AB  - In order to elucidate some conflicting data reported in the literature the
      diffusion kinetics between red blood cells (RBC) and plasma during dialysis were
      studied for urea, creatinine and uric acid. Several complementary studies were
      performed. According to our results urea diffuses very rapidly from RBC to plasma
      and is almost at equilibrium at the dialyser outlet; thus the extraction of urea
      during dialysis is from both plasma and RBC. On the other hand creatinine and
      uric acid hardly diffuse at all from RBC to plasma during blood transit through
      the hemodialyser and these solutes are thus extracted mainly from plasma. As a
      consequence an important in-vitro equilibration process occurs for both solutes
      in blood drawn at the dialyser outlet; the equilibration rate is greatly
      temperature-dependent and to achieve complete equilibrium at room temperature, up
      to 6 to 12 hours were needed for creatinine and 2 to 3 hours for uric acid.
      Moreover, in the case of creatinine, but not for uric acid, a RBC/plasma
      disequilibrium was also found in blood drawn at the dialyser inlet; this finding
      is in contrast with previous reports and suggests that with high-efficiency
      dialysis modalities the interval between two successive RBC transits through the
      dialyser may be insufficient for complete equilibration of slowly equilibrating
      solutes. The clinical implications of these findings with respect to the in-vivo
      dialyser performance and clearance determinations are discussed.

PMID- 8281717
TI  - The influence of dialyzer geometry on blood coagulation and biocompatibility.
AB  - The influence of dialyzer geometry on blood coagulation, heparin requirement and
      complement activation was studied in fourteen chronic hemodialysis patients. Each
      patient was dialyzed with two different cuprophan dialyzers, hollow fiber GF 120M
      and parallel plate Lundia IC5N. Both dialyzers had a wall thickness of 11
      microns, surface area of 1.2 m2 and both were sterilized with ethylene oxide.
      Heparin doses were individually titrated. The mean heparin dose was 6089 +/- 988
      U. Platelet count decreased from 218 x 10(9)/l to 193 x 10(9)/l and from 235 x
      10(9)/l to 197 x 10(9)/l respectively (hollow fiber/plate dialyzer, ns). The
      number of leucocytes decreased at 15 min after start of dialysis by 56% and 61%
      (hollow fiber/plate dialyzer, ns). The heparin requirement, measured as
      prolongation of whole blood activated coagulation time after identical doses of
      heparin, were the same in hollow fiber and plate dialysis sessions. The arterial
      fibrinopeptide A concentrations increased during dialysis from 5.4 to 7.1 nmol/l
      and 8.5 to 9.6 nmol/l respectively (hollow fiber/plate dialyzer, ns). The
      residual blood volume in the hollow fiber dialyzers was 1.3 +/- 1.1 ml and in the
      plate dialyzers 1.5 +/- 0.9 ml (ns). C3a activation, indicated by a marked
      arterio-venous difference, was observed at 15 min after start of dialysis with
      hollow fiber as well as plate dialyzers. The arterio-venous difference was less
      pronounced at the end of dialysis. There were no differences in C3a activation
      between hollow fiber and plate dialyzers at any timepoint. It is concluded that
      dialyzer geometry does not significantly influence platelet count, blood
      coagulation, heparin requirement or complement activation.

PMID- 8281719
TI  - Effects of omeprazole therapy on peptic disease and serum gastrin levels in
      hemodialysis patients. A preliminary study.
AB  - Hemodialysis patients are frequently affected by peptic disease, and in many
      cases they have high serum levels of gastrin. The aim of this study was to
      evaluate the effects of omeprazole, an inhibitor of gastric parietal cells
      hydrogen pump, on peptic disease and gastric secretion of 16 selected dialysis
      patients. H2-receptors blocking drugs or gastric acidity buffers were withdrawn
      for 2 weeks, then omeprazole was administered for 4 weeks at a daily dosage of 20
      mg. Before and after the omeprazole therapy, registration of subjective peptic
      symptoms, baseline serum gastrin dosage and endoscopy of upper digestive tract
      were performed. Before starting omeprazole, the serum gastrin value was 515 +/-
      180 pg/l, all the patients complained of peptic symptoms, and endoscopy showed: 8
      cases of duodenal ulcer, 3 cases of pyloric ulcer and 5 cases of antral erosive
      gastritis. At the end of the omeprazole treatment period, a slight but
      statistically not significant increase of serum gastrin level (537 +/- 198 pg/l)
      was observed. Twelve patients reported the total disappearance of symptoms of
      peptic disease, 3 patients a partial reduction, and 1 patient had no improvement.
      Control endoscopy showed the healing (white scar) of all the ulcers, and the
      disappearance of all the erosive lesions. In conclusion, our results show that a
      20 mg/day omeprazole short-term therapy can be given safely to uremic patients
      undergoing hemodialysis and is effective for a quick healing of active peptic
      lesions.

PMID- 8281720
TI  - W(h)ither diabetes care?

PMID- 8281721
TI  - Blood glucose monitoring: does technology help?

PMID- 8281722
TI  - Decreased plasminogen activator inhibitor-1 activity in newly diagnosed type 2
      diabetic patients following dietary modification.
AB  - Increased plasminogen activator inhibitor-1 (PAI-1) activity has been reported in
      Type 2 (non-insulin-dependent) diabetes and is a recognized risk factor for
      coronary artery disease. Fourteen newly diagnosed Type 2 diabetic patients were
      studied before and 3 months after standard clinical dietary modification. To
      assess the effect of improved metabolic control on PAI-1 activity, nine Type 2
      diabetic patients established on diet therapy and with previous stable glycaemic
      control served as controls. In the newly diagnosed patients diet therapy resulted
      in a significant decrease in HbA1c levels (8.3 +/- 0.5 vs 5.2 +/- 0.3% (mean +/-
      SEM); p < 0.001), and this was accompanied by a fall in fibrinogen (4.3 +/- 0.3
      vs 3.0 +/- 0.2 g.l-1; p < 0.01) concentration, and PAI-1 (18.7 +/- 2.3 vs 12.2 +/
      0.9 arbitrary units ml-1; p < 0.02) and factor VIII (147 +/- 17 vs 115 +/- 13%;
      P < 0.01) activities. PAI-1 activity was correlated with triglyceride levels at
      the first assessment in the newly diagnosed patients (r = 0.66; p < 0.01), and
      this was the only independent association by multiple regression analysis when
      all patients (n = 23) were considered (r = 0.62; p < 0.002). However, there was
      no association between the changes in PAI-1 activity and the changes in HbA1c
      BMI, and serum triglyceride levels following treatment in the newly diagnosed
      patients. Serum triglyceride concentrations, HBA1c, PAI-1 activity, and the
      coagulation factors remained unchanged in the control group over the same
      treatment period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281723
TI  - Incidence of microvascular complications in type 1 diabetic subjects with limited
      joint mobility: a 10-year prospective study.
AB  - Previous cross-sectional studies have shown a significant correlation between
      limited joint mobility (LJM) and the microvascular complications of Type 1
      diabetes, but whether LJM precedes and, therefore, may be regarded as an early
      marker for complications is unknown. Twenty-two Type 1 diabetic patients (10
      male/12 female; diabetes duration at follow-up 20.1 +/- 1.3 (SEM) years) with
      LJM, and 22 subjects matched for age, sex, and duration of diabetes, without LJM
      were observed over a 10-year period. Both groups were free of retinopathy and
      negative for 'dipstick' proteinuria at baseline. After 10 years, of 22 patients
      with LJM, 10 had developed background and 3 proliferative retinopathy compared
      with 9 and 1 control subjects, respectively. Microalbuminuria (20 < or = albumin
      excretion rate < 200 micrograms min-1) was present in 3 and macroalbuminuria
      (albumin excretion rate > or = 200 micrograms min-1) in 2 of LJM patients
      compared with 6 and 1 control subjects, respectively. Ankle and toe vibration
      perception thresholds, HbA1, mean HbA1 (a mean of serial HbA1 measurements
      obtained during the 10-year follow-up period), and arterial blood pressure did
      not differ between the two groups (p > 0.05). At 10-year review, 9 of the control
      subjects had developed LJM of whom 4 had retinopathy and 4 microalbuminuria.
      Thus, while LJM may be another 'chronic complication' of diabetes, its presence
      does not appear to predict those at increased risk of developing microvascular
      complications.

PMID- 8281724
TI  - Fasting plasma glucose in the diagnosis of diabetes mellitus: a study from
      southern India.
AB  - The usefulness of fasting plasma glucose (FPG) in the diagnosis of diabetes
      mellitus was assessed in Asian Indians in South India. Oral GTT values in 570
      newly screened adults were studied. Taking the WHO criteria of 2 h plasma glucose
      (PG) of > or = 11.1 mmol l-1 for diagnosis of diabetes, the validity of a FPG of
      > or = 7.8 mmol l-1 cut off value for diabetes was assessed. Using the regression
      analysis, the correlations of the FPG to 2 h PG were examined. Among the 268 with
      2h PG value of > or = 11.1 mmol l-1, 205 (76.5%) had FPG > or = 7.8 mmol l-1.
      Sensitivity of FPG was 76.5% for diagnosis of diabetes and its specificity was
      99%. An exponential regression model gave the best fit for FPG vs 2 h PG and
      using the regression equation, the predicted FPG for a 2 h PG of 11.1 mmol l-1
      was 7.05 mmol l-1. Sensitivity increased to 90.3% with FPG of 7.05 mmol l-1 while
      the specificity remained at 92%. It is concluded that in the south Indian
      subjects, the sensitivity for diagnosis of diabetes with FPG of > or = 7.8 mmol l
      1 was 76.5%; and it increased to 90.3% with FPG of > or = 7.05 mmol l-1.

PMID- 8281725
TI  - Plasma lipid levels at diagnosis in type 2 diabetic patients.
AB  - Plasma lipid measurements were obtained at the time that 545 subjects were
      screened for diabetes mellitus. Both the women and men diagnosed with diabetes
      had significantly higher triglyceride levels (p < 0.05) and lower high-density
      lipoprotein cholesterol (HDL-cholesterol) levels (p < 0.05) than those with
      normal glucose tolerance. Low-density-lipoprotein cholesterol (LDL-cholesterol)
      levels were only higher in the diabetic women (p < 0.001). Differences in lipid
      values were diminished somewhat with allowances for the waist-hip ratio. HDL
      cholesterol values were inversely related to fasting insulin levels in the
      normoglycaemic men and women (p < 0.01), but not in the diabetic individuals.
      Triglyceride levels were strongly positively related to insulin values in the
      normoglycaemic men and women (p < 0.001 for both), while associations tended to
      be smaller in the diabetic subjects. In 13 of the diabetic individuals who were
      not medicated for diabetes over a period of 17.5 +/- 4.6 months, changes in HDL
      cholesterol levels were positively related (p = 0.80, < 0.001) and changes in
      triglyceride levels inversely related (r = -0.70, p < 0.01) to changes in insulin
      values. These data indicate that at diagnosis Type 2 diabetic patients have an
      atherogenic lipid pattern that may be related in part to differences in adipose
      distribution. In addition, the data suggest that HDL-cholesterol is positively
      related and triglyceride inversely related to insulin action.

PMID- 8281726
TI  - Mortality in diabetic patients with cardiovascular autonomic neuropathy.
AB  - Cardiovascular autonomic diabetic neuropathy (CADN) may carry an increased risk
      of mortality. However, in previous studies the prognosis of patients with CADN
      seemed to be influenced by life-threatening macro- and microvascular
      complications which had already been present at the start of the study period.
      Between 1981 and 1983, 1015 diabetic patients have been examined for CADN
      (abnormal heart rate variation at rest and during deep respiration) at the
      Diabetes Research Institute, Dusseldorf. Thirty-five patients (28 with Type 1
      diabetes, 7 with Type 2 diabetes) with CADN have been retrospectively recruited
      and reviewed 8 years later and compared with 35 patients without CADN who were
      matched for sex, age, and duration of diabetes. Exclusion criteria for entry into
      the study included severe micro- or macrovascular complications, such as
      proliferative retinopathy, proteinuria or symptomatic coronary artery disease.
      During the 8-year observation period, 8 patients with CADN and 1 patient without
      CADN died. The survival rate estimates steadily declined in patients with CADN
      over the whole period studied. The 8-year survival rate estimate in patients with
      CADN was 77% compared with 97% in those with normal autonomic function (p <
      0.05). Deaths were mainly due to macrovascular diseases (n = 3) and sudden
      unexpected deaths (n = 3). One patient with CADN died after an episode of severe
      hypoglycaemia. Among the decreased patients, coefficient of variation of R-R
      intervals during deep breathing was significantly reduced when compared with
      those who survived (1.04 +/- 0.5% vs 1.87 +/- 1.0%; p < 0.05), and symptoms of
      autonomic neuropathy (orthostatic hypotension, gastroparesis, gustatory sweating)
      were more frequent (7/8 vs 10/27 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281727
TI  - Increased red cell sodium lithium countertransport activity, total exchangeable
      sodium, and hormonal control of sodium balance in normoalbuminuric type 1
      diabetes.
AB  - The relationship between erythrocyte sodium lithium countertransport activity
      (SLC), total exchangeable sodium (NaE), and hormonal control of renal function
      was examined in 40 normotensive, normoalbuminuric, non-neuropathic Type 1
      diabetic subjects, of whom 8 had elevated SLC (> 0.40 mmol Li h-1l-1 rbc). Eleven
      health controls with normal SLC, who were of comparable age, body mass, and blood
      pressure were also studied. By contrast with healthy controls, SLC in Type 1
      diabetes was not associated with plasma renin activity (PRA), aldosterone,
      systolic blood pressure or lean body mass. SLC was also unrelated to atrial
      natriuretic peptide (ANP) (Type 1 diabetes only) and NaE. NaE was not correlated
      with any other variables. The relationships between PRA and aldosterone in
      healthy controls were retained in Type 1 diabetes (R2 0.37 supine, p = 0.00001,
      and 0.27 ambulant, p = 0.0005), as were respective direct and inverse relations
      between vasopressin and ANP and both PRA (rs 0.54 to 0.57, rs -0.43 to -0.53),
      and aldosterone (rs 0.78 to 0.80, rs -0.71 to -0.80). Fasting free serum insulin
      and vasopressin were both inversely related to ANP (rs -0.91 and -0.71,
      respectively). In the absence of autonomic dysfunction, hypertension or early
      nephropathy in Type 1 diabetes, increased SLC or exchangeable sodium were
      unrelated to each other or with hormonal control of sodium balance, but the
      homeostatic factors controlling hormonal interaction appear to be maintained. The
      interaction between insulin and hormonal control of sodium and water balance may
      be modified by circulating free insulin concentrations.

PMID- 8281728
TI  - Insulin therapy increases low plasma growth hormone binding protein in children
      with new-onset type 1 diabetes.
AB  - This study was undertaken (1) to evaluate growth hormone binding protein (GHBP)
      levels in newly diagnosed patients with Type 1 diabetes before and after insulin
      therapy and (2) to determine the relationship of GHBP to glycaemic control, C
      peptide level and blood pH. GHBP, expressed as a percentage of (125I)GH bound,
      was determined in 33 patients with Type 1 diabetes (M/F = 19/14, 12.3 +/- 0.4
      years) before (day 0), after 5 days (day 5) and after 3 months (month 3) of
      insulin therapy. At day 0, GHBP was lower in Type 1 diabetes compared with 38
      matched healthy control subjects (3.9 +/- 0.4 vs 8.2 +/- 0.4%, p < 0.001). There
      was no significant improvement in GHBP at day 5 (4.4 +/- 0.3%). At month 3, GHBP
      increased to (6.0 +/- 0.4%, p < 0.001 vs day 0), but was still lower than
      controls, p < 0.001. At day 0 GHBP correlated with BMI (r = 0.50, p = 0.001),
      blood glucose (r = -0.43 p = 0.006) and pH (r = 0.48, p = 0.004), but not HbA1.
      GHBP at month 3 correlated with day 0 C-peptide (r = 0.41, p = 0.02). Thus, (1)
      circulating GHBP is low in newly diagnosed patients with Type 1 diabetes, and
      increases after 3 months of insulin therapy but does not normalize and (2) the
      severity of biochemical derangement and residual beta-cell function at diagnosis
      may determine GHBP status and its recovery. We conclude that insulin is an
      important modulator of GH binding protein in newly diagnosed children with Type 1
      diabetes.

PMID- 8281729
TI  - Reproducibility of the short insulin tolerance test.
AB  - The short insulin tolerance test is a simple method of estimating insulin
      resistance by measuring the rate of fall of blood glucose following the
      intravenous administration of insulin. To determine its reproducibility, 18
      healthy subjects underwent duplicate insulin tolerance tests separated by at
      least 1 week. Intravenous insulin (0.05 units kg-1) was administered into an
      antecubital vein and arterialized venous samples were obtained from a
      retrogradely cannulated vein on the dorsum of the hand on the same side. The test
      was terminated with an intravenous glucose injection 15 min after the
      administration of insulin. The mean whole blood glucose concentration fell from
      4.6 mmol l-1 to 2.8 mmol l-1 while plasma insulin concentrations rose to
      supraphysiological levels and declined exponentially. The glucose disappearance
      rate (Kitt) calculated from the slope of the fall in log transformed blood
      glucose between 3 and 15 min after insulin injection ranged from 2.1 to 6.5 (mean
      4.4) % min-1 during the first visit and 1.7 to 7.4 (mean 4.4) % min-1 during the
      second. The ratio of the within-subject to between-subject variance of the test
      was 0.24, the within-subject coefficient of variation was 13% and the between
      subject coefficient of variation 26%. The short insulin tolerance test is
      reproducible and could be used to measure insulin resistance in large-scale
      epidemiological studies.

PMID- 8281730
TI  - The clinical diagnosis of sensory neuropathy in elderly people.
AB  - Minor abnormalities in sensory perception are common in elderly people but the
      significance of these findings is uncertain. In order to define the most relevant
      clinical tests for the diagnosis of significant neuropathy in the elderly
      diabetic patient, quantified perception of vibration, temperature, pain, and
      light touch was assessed in 200 (100 hospitalized, 100 community) consecutive non
      diabetic elderly subjects without apparent neurological disease, using an
      established scoring system. The changes in sensory perception were similar in the
      two groups and data were pooled for further analysis. Progressive loss of
      peripheral sensation was apparent with increasing age (neuropathy deficit score
      vs age: r = .04, p < 0.0001). Loss of vibration perception was particularly
      marked; deficit scores for vibration were significantly lower in the < 70 years
      age group than in all the older age groups (vibration score: < 70 years vs 80-84
      years mean (95% CI) 0.89 (0.54) vs 3.02 (0.6), p < 0.0001). In contrast,
      perception of light touch and pain was relatively preserved in old age.
      Assessment of vibration perception is of limited value in elderly people since
      the distinction between 'normal ageing' and significant neuropathy is unclear.
      Perception of light touch and pain are likely to be the most reliable clinical
      indicators of significant neuropathy in an elderly diabetic population.

PMID- 8281731
TI  - Low literacy: a problem in diabetes education.
AB  - Eighty-five diabetic patients who were proficient in English were studied to
      assess the impact of educational material of varying literacy levels on patient
      comprehension. Two samples of available diabetes foot care material of Grade 11
      and 9 readability (measured by SMOG formula) and purposely written in-house
      material of Grade 6 readability were used. Patients were randomized to read
      information of either Grade 6 and Grade 11 or Grade 6 and Grade 9 readability.
      Socio-demographic data and reading habits were collected to allow for
      identification of literacy markers. The mean CLOZE score (a measure of
      comprehension) was better in patients who read the Grade 6 information than for
      both the Grade 11 and Grade 9 information (59.5 +/- 11.8, 46.8 +/- 22.0, 45.8 +/-
      22.2 respectively, p < 0.001). When evaluated in terms of percent of patients
      that could independently understand the material, Grade 6 information
      outperformed the Grade 11 and Grade 9 information (60%, 19%, 21%, respectively, p
      < 0.001). For the Grade 11 and Grade 9 information, poorer comprehension was
      associated with a non-English speaking background, early school leaving age,
      infrequent reading habits, and preference for tabloids (p < 0.02). Comprehension
      when patients read the Grade 6 information was no longer dependent on two of the
      four identified literacy markers. We conclude that reducing literacy demands of
      health literature improves patients' comprehension. Attention to socio
      demographic data and reading habits can assist educators in assessing patients'
      literacy status and ensuring patients are given literature of compatible
      readability.

PMID- 8281732
TI  - Coping behaviour and degree of discrepancy between retrospective and prospective
      self-ratings of change in quality of life in type 1 diabetes mellitus.
AB  - Quality of life and metabolic control were examined in 74 adults with Type 1
      diabetes mellitus in 1988. Sixty-six of the persons were followed up in 1990 with
      the aim of studying more closely the subgroup that showed a 'major' discrepancy
      between 'retrospective' and 'prospective' quality of life change ratings.
      'Prospective' quality of life change was defined as the difference in assessed
      quality of life status between 1990 and 1988. 'Retrospective' quality of life
      change was assessed directly by subjects in 1990 covering the same time period.
      Data on quality of life, well-being, sociodemographics and metabolic control were
      collected on both occasions. Recent life-change events and long-term
      complications were also recorded in 1990. Subjects with 'major' discrepancy
      reported greater retrospective quality of life improvement, higher quality of
      life, and greater well-being, as well as lesser occurrence of negative and
      greater occurrence of positive recent life-change events, than did those with
      'minor' discrepancy, despite their exhibiting poorer metabolic control and a
      higher prevalence of incipient nephropathy. The results are discussed in terms of
      possible coping and defence strategies.

PMID- 8281733
TI  - The first two years of type 1 diabetes in children: length of the initial
      hospital stay affects costs but not effectiveness of care.
AB  - The long-term costs of care and the effects of the length of the initial hospital
      stay on costs and effectiveness of the care of children with Type 1 diabetes are
      largely unexplored. A randomized prospective study was carried out wherein we
      shortened the length of the initial hospital stay from 23 +/- 4 days to 9 +/- 3
      days in half of 61 consecutive children with newly diagnosed Type 1 diabetes.
      Metabolic control, psychosocial adjustment, and direct and indirect costs of care
      were compared during a 2-year follow-up. Having confirmed similar metabolic and
      psychosocial outcomes, we now report the costs of the two treatment modes. The
      costs of care of a child with Type 1 diabetes totalled 10,834 pounds and 6928
      pounds in the long-term and short-term alternatives, respectively, during the 2
      year follow-up (p < 0.001, one-way ANOVA). Direct costs accounted for 83% of the
      expenses in the long-term and 82% of the expenses in the short-term group; 73%
      and 56% of the direct and 78% and 72% of the indirect costs were incurred during
      the first month in the two groups, respectively. The first month's expenses were
      twice as high in the long-term than in the short-term group. Consumed hospital
      days and the parents' lost work time were the largest cost items in both groups.
      There were no significant differences in the cost items during the following 23
      months. We conclude that the greater part of both the direct and the indirect
      expenditures were associated with the initial hospital stay.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8281734
TI  - Insulin requirements in lipodystrophic diabetes.
AB  - A ten-fold increase in daily insulin requirements during the administration of
      total parenteral nutrition (TPN) is described in a patient with congenital
      generalized lipodystrophy, insulin-requiring diabetes mellitus, and acanthosis
      nigricans during an episode of acute pancreatitis secondary to
      hypertriglyceridaemia. After a period of 13 days on TPN, insulin requirements
      increased dramatically to an average of 1428 units per day for a period of 12
      days, to achieve a mean blood glucose level of 10.9 mmol l-1. When the patient
      resumed feeding and the TPN was discontinued, the average daily insulin
      requirement was 104 units with a mean 24 h blood glucose of 11.8 mmol l-1.
      Parenteral administration of energy substrates in a rare case of diabetes
      mellitus and congenital lipodystrophy complicated by acute pancreatitis resulted
      in a severe insulin insensitive state due to the combination of the
      hypermetabolism conferred by the pancreatitis plus transient impairments of the
      glucose disposal mechanism by the energy substrates provided.

PMID- 8281735
TI  - Incidence and prevalence of type 1 diabetes in children and adolescents in
      Benghazi, Libya.
AB  - The mean annual incidence rates of Type 1 diabetes mellitus in Arab children and
      adolescents in Benghazi, Libya were assessed as based on prospective registration
      of patients during the period 1981-1990. Results showed an annual incidence (per
      100,000) of 7.0 (6.0-8.2) (males 6.3(5.0-7.9) females 7.8(6.3-9.7)) in 0-14 year
      olds and 8.8(7.8-10.0) (males 8.3(6.9-10.0), females 9.2(7.7-11.0)) in 0-19 year
      olds. There were no significant differences between males and females or between
      season of onset. The commonest age of onset was 15-19 years. Annual variations
      were significant in the 0-14 years age group (p < 0.001) and non-significant in
      the 0-19 years age group. In 1981 the age adjusted prevalence rates of Type 1
      patients (per 100,000) were 23.5 (17.1-31.5) (males 21.2(13.1-32.3), females
      25.9(16.8-38.3)) in 0-14 year olds and 36.2(29.1-45.1) (males 31.4(22.2-43.2),
      females 41.0(30.2-54.5)) in 0-19 year olds. In 1990 the prevalence rates had
      increased to 37.3(30.5-45.5) (males 40.7(30.8-53.3), females 33.8 (24.6-45.3)) in
      0-14 year olds and 59.5(51.6-58.5) (males 60.3(49.3-73.6), females 58.6 (47.7
      72.1)) in 0-19 year olds. Increase in prevalence rates was significant in both
      sexes and in both age groups (p < 0.001). Increase in prevalence rates in girls
      in 1981 and in boys in 1990 were not significant. It is concluded that Type 1
      diabetes is a common chronic disease of children and adolescents in Benghazi,
      Libya.

PMID- 8281736
TI  - Assessment of diabetes education in the teaching hospital, Addis Ababa, Ethiopia.
AB  - With the aim of assessing continuing diabetes education and obtaining baseline
      information, we have evaluated the knowledge of 139 randomly selected diabetic
      patients from the Diabetes Clinic of Tikur Anbessa Teaching Hospital, Addis
      Ababa, Ethiopia. Seventy-five Type 1 (insulin-dependent) and 64 Type 2 (non
      insulin-dependent) diabetic patients, with a mean age of 36 +/- 14 (+/- SD)
      (range 15-78, median 36) years, and mean duration of known diabetes 6.3 +/- 5.5
      (range 1-30, median 5) years participated in the study. Knowledge was assessed by
      a questionnaire which examined three principal areas: general knowledge on
      diabetes mellitus, diet plus self care, and chronic complications. Twenty-eight
      (20.1%), did not attend any and 59 (42.5%) attended the diabetes education
      programme more than once. The Adjusted Percentage Score (APSCORE) was 69 +/- 1.4
      (SEM). Type 1 diabetic patients had a significantly higher score (p < 0.001) for
      overall knowledge when compared to Type 2 patients. In both groups the knowledge
      on chronic complications was very poor when compared to the other areas (p <
      0.001). No sex difference in knowledge was seen. Higher school and diabetes
      education attendance had a significant influence on the knowledge of diabetes.
      However, better knowledge about diabetes was not associated with better glycaemic
      control as measured by the fasting blood glucose concentration. The wide
      difference in knowledge, the low rate of attendance at diabetes education
      sessions, and the very low awareness about chronic complications is very
      worrying. To achieve the intended aim the diabetes education programme needs to
      be revised.

PMID- 8281737
TI  - Dietary recommendations for children and adolescents with diabetes: an
      implementation paper. British Diabetic Association's Professional Advisory
      Committee.
AB  - General Recommendations: 1. Children with diabetes mellitus have the same basic
      nutritional requirements as other children. 2. Dietary recommendations should be
      based on good eating habits for the whole family. Radical changes in diet
      involving unusual foods or eating patterns for the child with diabetes alone are
      not appropriate. 3. Energy requirements of children vary widely and the energy
      content of the diet should be based on what the child usually eats. The diet
      should be reviewed regularly to meet the changing needs of growth and physical
      exercise without obesity. 4. The insulin regimen should, as far as is possible,
      be chosen to fit the child's daily lifestyle and preferred eating habits. Insulin
      type, dose, and frequency should be reviewed with the diet as the child develops.
      5. Regular distribution of meals and snacks throughout the day remains the most
      important way to avoid extremes of hyperglycaemia and hypoglycaemia. This
      distribution should be based on an exchange system, using handy measures and
      taking into account food and meal type, the particular insulin regimen and the
      child's exercise patterns and usual eating habits. Currently this exchange system
      is based on carbohydrate foods but in the future the energy and fat contents will
      need further consideration. 6. Most special 'diabetic foods' are unnecessary. Low
      calorie sweeteners, as used in low calorie fruit squashes and fizzy drinks, are
      useful. 7. Children with diabetes from specific ethnic minority groups, or on
      vegan diets or living in deprived circumstances require special dietary attention
      for their diabetes. Those with coexisting chronic disorders such as cystic
      fibrosis or coeliac disease, should receive dietary advice from professionals
      with specialist knowledge. 8. Translating the principles of diabetic dietary
      management into a varied diet, arranged readily by the parents and eaten by the
      child, is demanding. It can best be met by a skilled dietitian working in close
      co-operation with child, parents, diabetes specialist nurse and doctor. Infancy
      9. The diet should not differ from that of infants without diabetes. Breast
      feeding should be encouraged or a standard infant formula-feed used. Solids may
      be introduced from 3-6 months, but breast milk or a modified infant formula is
      encouraged as part of the increasingly mixed diet to at least the end of the
      first year. 10. Diabetes is rare in infancy so expert advice should be sought
      from dietitians experienced in paediatric diabetes. Under fives: 11.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8281738
TI  - Leishmaniasis: report of 33 cases and a review of the literature.
AB  - Leishmaniasis are parasitic diseases in extension. They appear in new foci,
      because of important displacements of populations, and they affect
      immunocompromised patients (under chemotherapy, transplanted, or HIV infected).
      Study of 33 cases of leishmaniasis, 22 visceral and 11 cutaneous, at the Hopital
      du Kremlin-Bicetre, France, showed predominant contamination in Maghreb and in
      the south of France. In the case of Kala-Azar, fever (18 cases) and
      hepatosplenomegaly (19 cases) are frequent, and the serodiagnosis and the search
      of parasites by myelogram are always positive. In HIV-infected individuals,
      clinical signs are similar, but the serodiagnosis is less reliable. Evolution is
      bad in transplanted patients who must remain under immunosuppressive drugs. In
      the case of cutaneous leishmaniasis, diagnosis is based on local sample, while
      the serodiagnosis remains negative. Treatment is sometimes long, necessitating
      repeated treatments.

PMID- 8281739
TI  - Fatal septicaemia caused by Aeromonas hydrophila in a patient with cirrhosis.
AB  - In this case report from Italy we describe a fatal infection caused by A.
      hydrophila in a 39 yr old cirrhotic patient. This pathogen was isolated as a pure
      single culture from the patient's blood sample. The patient died on the second
      day of hospitalization from overwhelming sepsis. The A. hydrophila isolate was
      tested for different potential virulence properties, such as invasiveness,
      adherence, exotoxins production, presence of fimbriae and for the patterns of
      resistance to a variety of antimicrobial agents. Although, the Aeromonas species
      are infrequently reported as a cause of human infections, the present case study
      confirms the capability of these pathogens to induce serious human infections.

PMID- 8281740
TI  - Rinderpest vaccination responses among calves and adult cattle in Uganda
      monitored using ELISA assay.
AB  - Responses to the Plowright Rinderpest vaccine by 43 calves and 70 adult cattle in
      Uganda in 1990, through the production of IgG antibodies, were monitored for 4
      weeks using the ELISA assay. 80% of the calves were seronegative before
      vaccination of which 32% remained seronegative and 68% subsequently seroconverted
      at 2 weeks postvaccination. 20% of the calves were seropositive before
      vaccination but registered a decline during the 2nd and 4th weeks
      postvaccination. 50% of adult Ankole cattle seroconverted after 3 weeks
      postvaccination, while the other 50% of them, which were seropositive before
      vaccination, showed a decline in seronegative levels during the first 2 weeks
      postvaccination, but increased again at the 4th week. 90% of Friesian adult
      cattle were seronegative before vaccination; however, they all seroconverted
      within the 2nd week of postvaccination. The other 10% remained seropositive, with
      a slight decline of antibody levels during the 4 weeks after vaccination.

PMID- 8281741
TI  - Arachidonic acid immunoregulation in lambs persistently infected with border
      disease virus.
AB  - To evaluate arachidonic acid-related immunoregulatory mechanisms during long-term
      persistent pestivirus infection, we measured plasma contents of leukotriene C4
      (LTC4), prostaglandin D2 (PGD2) and their plasma fatty acid (FA) precursor,
      arachidonic acid (AA), in six lambs with congenital border disease (BD).
      Significantly elevated average plasma LTC4 during the first half year of life was
      associated with increased PDG2 when compared to uninfected control lambs.
      Significantly elevated total plasma esterified AA stores suggest an effective BDV
      mediated prostenoid immunostimulation. However, at 1 yr old, prostenoid secretion
      had fallen to normal (LTC4) or below normal (PGD2) levels. In contrast, there
      remained significantly elevated plasma esterified AA, present as available
      substrate for formation of these anti-viral immunoregulatory agents. These
      results suggested that preventing mobilization of AA from lipid stores for
      effective immune responses may be a viral strategy of BD virus that is associated
      with long term border disease effects.

PMID- 8281742
TI  - Optimization of culture conditions for feline x murine heterohybridomas.
AB  - Feline splenocytes were fused to the murine myeloma lines NSO or Ag8. Autologous
      serum and taurine were used as media supplements for the cat x mouse
      heterohybridomas. The best results were obtained by the use of NSO as fusion line
      with taurine-supported media.

PMID- 8281743
TI  - Reactions of sera from laboratory, domestic and wild animals in Africa with
      protein A and a recombinant chimeric protein AG.
AB  - An ELISA was developed to determine the reactivity of peroxidase labelled Protein
      A and a recombinant Protein A + Protein G construct, to sera from a variety of
      laboratory, domestic and wild animals from Africa. There was variability in the
      binding capacity of sera from individuals of the same species, but four groups
      could be recognized. Sera from birds and crocodiles were at most weakly reactive
      with either Protein A or the chimeric construct. Sera from some domestic animals
      such as horse, goat and cat, and sera from some wild ungulates including buffalo,
      wildebeest, waterbuck and impala were reactive with Protein A, but reacted to a
      much greater degree with the chimeric construct. Sera from larger wild animals
      such as elephant, rhinoceros and giraffe were strongly reactive with the chimeric
      protein and moderately reactive with Protein A. Sera from primates and dog, pig,
      guinea pig and rabbit reacted strongly with both proteins. Chimeric proteins that
      combine the IgG binding capacities of Protein A and Protein G can be used to
      detect immunoglobulin from a wide variety of African wild animal species. They
      may thus be of great value in seroepidemiological investigations of these animal
      populations.

PMID- 8281744
TI  - Studies on experimental chlamydial mastitis in goat histoenzymology.
AB  - Two strains of Chlamydia psittaci (one isolated from aborted goat foetus and the
      other from brain of a buffalo calf that had died of meningoencephalitis) were
      injected intracisternally into six goats to produce experimental mastitis.
      Cryostat sections of 7-8 microns thickness, obtained from udder, teat, liver and
      kidney of infected and control animals were incubated for histoenzymic
      demonstration of alkaline-(AKPase), acid-(ACPase) and adenosine-tri-(ATPase)
      phosphatases; lactate-(LDH) and succinate-(SDH) dehydrogenases and for reduced
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-D). Results
      demonstrated that AKPase and NADPH-D declined while ACPase accumulated in acinar
      cells of udder while both NADPH-D and ACPase decreased in teat sinus epithelium.
      Hepatic canaliculi in perilobular areas of liver lobules registered complete
      absence of AKPase and ATPase. Hepatocytes and renal tubules accumulated LDH, SDH
      and NADPH-D. The interstitial connective tissue of udder and kidney presented
      higher levels of AKPase. Comparison of results with biochemical alterations in
      the level of these enzymes revealed striking discrepancies which seem to arise
      because of failure of biochemical procedures to discriminate between functional
      cells of tissue and inflammatory cells. The functional significance of
      histoenzymic alterations has been discussed.

PMID- 8281745
TI  - Studies on some biochemical characteristics of Staphylococcus aureus of buffalo
      mammary origin.
AB  - A total of 49 isolates of Staphylococcus aureus of buffalo mammary origin were
      studied for biochemical characteristics. Coagulase production, clumping factor,
      haemolytic activity, pigment production and fermentation of maltose and mannitol
      were employed to differentiate S. aureus from S. hyicus and S. intermedius. Out
      of 49 isolates, 97.95, 93.87, 93.87, 89.79, 95.91, 100.0, 95.91, 59.18, 100.0,
      100.0, 100.0, 89.79, 91.83 and 100.0% isolates were positive for coagulase
      production, protein-A production, haemolysin production, thermostable nuclease
      production, deoxyribonuclease production, tellurite reduction, nitrate reduction,
      lipase production, phosphatase production, mannitol fermentation, glucose
      fermentation, M.R. test, V.P. test and pigment production respectively. The only
      isolate from which coagulase production could not be detected, however, showed
      haemolytic activity, protein-A productivity, pigmentation and mannitol
      fermentation. One of the protein-A negative isolate was coagulase positive and
      showed mannitol fermentation, pigmentation and haemolytic activity. The study
      revealed that the biochemical characteristics of S. aureus of buffalo mammary
      origin did not differ from those of cattle origin. Coagulase, haemolysin,
      thermostable nuclease, deoxyribonuclease, phosphatase, lipase, tellurite and
      nitrate reduction closely related with protein-A. The presence of protein-A seems
      to be as reliable an indicator for S. aureus of buffalo origin as is coagulase
      production.

PMID- 8281746
TI  - Antibody dependent haemolysin, complement and opsonin in sera of a major carp,
      Cirrhina mrigala and catfish, Clarias batrachus and Heteropneustes fossilis.
AB  - The present communication is a continuation of our earlier study on the natural
      serum haemagglutinin/lectins of Cirrhina mrigala, Clarias batrachus and
      Heteropneustes fossilis. Sera of Cirrhina mrigala, belonging to the major carp
      family, could not only agglutinate heterologous rabbit erythrocytes, but also
      lyse them spontaneously. This lysis of rabbit RBC by Cirrhina mrigala sera was
      calcium ion dependent and heat sensitive, indicating thereby that the haemolysis
      was mediated by the fish serum complement system via the classical pathway.
      Quantification of CH50 and APCH50 levels in the sera of Clarias batrachus and
      Heteropneustes fossilis as well as in the sera of amphibia, aves and mammals
      showed that lower vertebrates predominantly possessed an alternative pathway of
      the complement system, while on the other hand, in the higher vertebrates the
      major pathway of complement activation was classical. Furthermore sera of Clarias
      batrachus and Heteropneustes fossilis had opsonins, which could stimulate
      heterologous rat peritoneal macrophages to engulf Staphylococcus aureus with the
      production of superoxide anion. From this study we concluded that fishes have
      been armed with various powerful natural humoral defense systems for their
      protection against environmental pathogens.

PMID- 8281747
TI  - Myosin polymorphism and differential expression in adult human skeletal muscle.
AB  - 1. Myosin heavy chain (HC) and light chain (LC) isoforms are expressed in a
      tissue-specific and developmentally-regulated manner in human skeletal muscle. 2.
      At least seven myosin HC isoforms are expressed in skeletal muscle of the adult.
      3. Histochemically-delineated fibre types (based on the stability of myofibrillar
      actomyosin adenosine triphosphatase activity) in limb muscles correlate with the
      myosin HC content. 4. Alterations in the phenotypic expression of myosin provides
      a mechanism of adaptation to stresses placed upon the muscle (e.g. increased and
      decreased usage).

PMID- 8281748
TI  - Antioxidant systems and erythrocyte life-span in mammals.
AB  - 1. Erythrocyte antioxidant systems--superoxide dismutase (SOD), catalase (CAT),
      reduced glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione S
      transferase (GST) and glutathione reductase (GR)--were discussed in relation to
      life-spans in some mammalian species. 2. The erythrocyte life-span of different
      mammals was found to be correlated with the levels of SOD, GSH-Px and GSH. 3.
      Data reviewed indicates that the erythrocyte life-span of each species is
      governed by both the oxygen radical formation and the efficiency of intrinsic
      antioxidant systems.

PMID- 8281749
TI  - Evolutionary changes in the genetic code.
AB  - 1. The genetic code was thought to be identical ("universal") in all biological
      systems until 1981, when it was discovered that the coding system in mammalian
      mitochondria differed from the universal code in the use of codons AUA, UGA, AGA
      and AGG. 2. Many other differences have since been discovered, some in
      mitochondria of various phyla, others in bacteria, ciliated protozoa, algae and
      yeasts. 3. The original thesis that the code was universal and "frozen" depended
      on the precept that any mutational change in the code would be lethal, because it
      would produce widespread alterations in the amino acid sequences of proteins.
      Such changes would destroy protein function, and hence would be intolerable. 4.
      The objection was "by-passed" by nature. It is possible for a codon to disappear
      from mRNA molecules, often as a result of directional mutation pressure in DNA:
      thus all UGA stop codons can be replaced by UAA. 5. The missing UGA codon can
      then reappear when some UGG tryptophan codons mutate to UGA. The new UGA codons
      will be translated as tryptophan, as is the case in non-plant mitochondria and
      Mycoplasma. Therefore, no changes have taken place in the amino acid sequences of
      proteins. 6. Variations of this procedure have occurred, affecting various
      codons, and discoveries are still being made. The findings illustrate the
      evolutionary interplay between tRNA, release factors and codon-anticodon pairing.

PMID- 8281750
TI  - Polymorphism of alpha-1 antitrypsin in dogs.
AB  - 1. A genetically determined polymorphism of alpha-1 antitrypsin is demonstrated
      in dog serum by isoelectric focusing in a pH range of 3.5-5.0, followed by direct
      immunoblotting using a specific antiserum. 2. Alpha 1 antitrypsin focuses as two
      major bands at isoelectric points of 4.60 and 4.64 or 4.67 and 4.7 in presumed
      homozygous animals. Heterozygotes show both sets of bands. 3. The results of
      seven crosses with 33 offspring are best explained by two codominant alleles, PiM
      and PiS at a single locus designated as Pi for proteinase inhibitor. 4. The
      concentration of alpha-1 antitrypsin in serum of healthy dogs was 2.65 +/- 0.42
      mg/ml and 2.19 +/- 0.38 mg/ml in females and males respectively. 5. The higher
      concentration in female dogs suggests that estrogens may influence the serum
      level of alpha-1 antitrypsin.

PMID- 8281751
TI  - Atrial natriuretic peptides in the heart and hemolymph of the oyster, Crassostrea
      virginica: a comparison with vertebrates.
AB  - 1. The content of atrial natriuretic peptides (ANPs) in the auricles of oysters,
      Crassostrea virginica, was significantly (P < 0.01) greater than in their
      ventricles. 2. High-performance gel permeation chromatography (HP-GPC) followed
      by ANF radioimmunoassay revealed two peaks in both oyster and vertebrate (rat)
      hearts--a major peak where the 12.6-14 kDa ANF prohormone elutes and a smaller
      peak where the pure human form of ANF elutes. 3. HP-GPC evaluation followed by
      proANF 31-67 radioimmunoassay revealed only an ANF-like prohormone while HP-GPC
      followed by proANF 1-30 radioimmunoassay revealed the ANF prohormone and a proANF
      1-30-like peptide in oyster and rat hearts. 4. ANPs concentrations in hemolymph
      were 940 +/- 129, 225 +/- 25, and 100 +/- 10 pg/ml by the proANF 1-30, proANF 31
      67, and ANF radioimmunoassays, respectively. 5. Atrial natriuretic-like peptides
      are present in the oyster heart in molecular species similar to vertebrate
      species and these peptides are also present in hemolymph.

PMID- 8281752
TI  - Detection of 180 kDa proteins in electroplax sodium channel preparations.
AB  - 1. Co-isolating proteins (M(r) 170,000-220,000) from sodium channel preparations
      made from the electric organ of the electric eel (Electrophorus electricus) were
      detected on Western blots using monoclonal antibodies. 2. Similar protein
      patterns were seen on immunoblots containing immunoprecipitated protein from eel
      muscle and brain tissues but not heart. 3. These co-isolating proteins could be
      separated from the mature TTX-sensitive channel protein (M(r) 280,000) using a
      lentil lectin-Sepharose column. 4. The 180 kDa proteins do not appear to be
      channel-related and can be detected as contaminants in electroplax sodium channel
      preparations using the monoclonal antibodies described here.

PMID- 8281753
TI  - A comparative study of vertebrate eye lens crystallins using isoelectric focusing
      and densitometry.
AB  - 1. The crystallin proteins of numerous species belonging to different classes of
      vertebrates have been studied. 2. Species-specific crystallin patterns are
      revealed which unequivocally characterize the different species. 3. A marked
      variability in the number and percentage of alpha-, beta- and gamma-crystallins
      were found in the various species. 4. The gamma-crystallin family, with a meagre
      number of common bands, has proved to be most representative of the species. The
      beta-crystallins, with their greater number of common bands, have been best
      preserved throughout vertebrate evolution. 5. From the similarity coefficient
      matrix a dendrogram is drawn up, a visual phylogenetic summary of the
      interrelationships between the vertebrates considered. 6. In the Discussion,
      other aspects are considered, such as lens morphology, functionality, animal age,
      post-synthetic modifications and genetic factors.

PMID- 8281754
TI  - Hemorrhagic and Mojave toxins in the venoms of the offspring of two Mojave
      rattlesnakes (Crotalus scutulatus scutulatus).
AB  - 1. The venoms of two Mojave rattlesnakes and those of their offsprings were
      analyzed for Mojave toxin and hemorrhagic toxin. 2. The venom of one female,
      collected in Pima County, Arizona, and the venoms of her six offspring contained
      hemorrhagic toxin but not Mojave toxin (venom B). 3. The venom of the second
      female, captured in El Paso County, Texas, contained both toxins (A+B venom). Of
      her 10 offspring, five contained venom with both toxins, two had hemorrhagic
      toxin only, and three contained neither toxin. 4. Venoms that caused hemorrhage
      also inactivated complement. A pool of the venoms of the venom B offspring was
      less toxic than adult pooled venom A.

PMID- 8281755
TI  - Mammalian glycine N-methyltransferases. Comparative kinetic and structural
      properties of the enzymes from human, rat, rabbit and pig livers.
AB  - 1. Human liver contains a rather high level of glycine N-methyltransferase. 2.
      The enzymes from human, rat, rabbit and pig livers are all tetramers and exhibit
      positive cooperativity toward S-adenosylmethionine and Michaelis-Menten kinetics
      toward glycine. The [S]0.5 values for S-adenosylmethionine and glycine of the rat
      enzyme are considerably lower than those of three other enzymes. 3. The subunit
      of rat glycine N-methyltransferase is shorter by two residues compared with the
      subunits of human, rabbit and pig glycine N-methyltransferases. Except for this
      difference, however, all enzymes show a high degree of sequence homology.

PMID- 8281756
TI  - Heat-stress response of broiler cockerels to manipulation of the gonadal
      steroids, testosterone and estradiol.
AB  - 1. Estradiol supplementation resulted in heat-stress mortality in both intact and
      caponized cockerels accompanied by depressed plasma corticosterone. 2. Phenotype
      selection for large comb and high plasma testosterone increased heat tolerance
      which was attributed to an increased plasma corticosterone. 3. The results
      suggested that the presence of testosterone had a positive influence on the heat
      tolerance of broiler cockerels.

PMID- 8281757
TI  - The effect of enzyme replacement on red cell adenine deoxyribonucleotides in
      adenosine deaminase-deficient erythrocytes of the opossum, Didelphis virginiana.
AB  - 1. Polyethyleneglycol-modified bovine adenosine deaminase was administered (10-20
      U/kg/week) intramuscularly to two opossums for 15 weeks and changes in red cell
      adenine ribo- and deoxyribonucleotides quantitated by HPLC. 2. Only a moderate
      decline of erythrocyte dAXP was observed at the end of the study when compared to
      results of enzyme replacement seen in human adenosine deaminase deficient
      patients. 3. Opossum red cells salvage substantial amounts of deoxyadenosine
      provided in physiologic (50 nM) concentration from plasma having either low or
      high adenosine deaminase activity.

PMID- 8281758
TI  - 2'-Deoxyadenosine metabolism in human and opossum Didelphis virginiana
      erythrocytes in vitro.
AB  - 1. In erythrocytes of both species, deamination and phosphorylation of dADO was
      completely inhibited by 5 microM 2'deoxycoformycin and 10 microM 5-ITU
      respectively. 2. Under physiologic conditions, provided with nanomolar
      concentrations of dADO there was complete deamination of dADO in human red cells.
      In opossum erythrocytes deamination and phosphorylation of the deoxynucleoside
      were nearly; additionally, 1-2% of the substrate was metabolized to AXP. 3. With
      ADA inhibited in intact red cells, apparent Km and Vmax for dADO were 0.5 vs 0.1
      mM and 0.8 vs 6.25 mumol/g hg/hr in human and opossum cells, respectively. 4. In
      opossum red cell lysates, GTP was superior to ATP and to dATP as a phosphate
      donor in the dADO kinase reaction.

PMID- 8281759
TI  - Expression of parathyroid hormone-related peptide gene in the rat hypothalamus.
AB  - 1. Parathyroid hormone-related peptide (PTHrP), originally isolated from human
      malignant tumors, is present in a variety of normal mammalian tissues, including
      the brain. 2. The expression and translation of the PTHrP gene within the rat
      hypothalamus was demonstrated in this study by the specific hybridization of a
      1.8 kb mRNA product with a PTHrP cDNA probe and by the crossreactivity of rat
      hypothalamic extracts in a PTHrP radioimmunoassay. 3. These results suggest roles
      for PTHrP in neural or hypophysiotropic regulation.

PMID- 8281760
TI  - A comparative study on the biological properties of venoms from juvenile and
      adult common tiger snake (Notechis scutatus) venoms.
AB  - 1. The biological properties of venoms from juvenile and adult common tiger
      snakes (Notechis scutatus) were compared. 2. The lethality, procoagulant activity
      and enzymatic activities of the juvenile venom were not substantially different
      from those of the adult venom. 3. Electrophoretic studies, however, indicated
      some minor differences in the protein composition of the juvenile and adult
      venoms.

PMID- 8281761
TI  - Development of an enzyme immunoassay for arginine-vasopressin (AVP)-like insect
      diuretic hormone.
AB  - 1. The AVP-like insect diuretic hormone is a biologically active antiparallel
      dimer present, along with its non-active monomeric form (Cys-Leu-Ile-Thr-Asn-Cys
      Pro-Arg-GlyNH2), in the African locust. 2. It exhibits diuretic activity by
      increasing fluid excretion at the level of the Malpighian tubules. 3. To date,
      both monomer and dimer have been assayed using a radioimmunoassay originally
      prepared for mammalian AVP. 4. We have developed here an original enzyme
      immunoassay based on the use of antibodies to insect AVP-like raised in rabbits
      against synthetic monomers and dimers, using acetylcholinesterase conjugate as an
      enzymatic tracer. 5. This enzyme immunoassay enables measurement of the dimer to
      be made with adequate sensitivity (0.3 nmol/l, i.e. 21 pg/well) and
      reproducibility while sensitivity of the monomer is somewhat lower (14 nmol/l,
      i.e. 480 pg/well). 6. The assay was validated by assaying native dimer and
      monomer throughout the different steps of purification (from a crude extract to
      reversed-phase liquid chromatographic fractions). 7. A good correlation was
      observed between radioimmunoassays and enzyme immunoassays. 8. The enzyme
      immunoassay was also used to measure the level of AVP-like peptides in several
      insect tissues not explored to date.

PMID- 8281762
TI  - A novel role of Periplaneta lectin as an opsonin to recognize 2-keto-3-deoxy
      octonate residues of bacterial lipopolysaccharides.
AB  - 1. Periplaneta lectin of the American cockroach was shown to have affinity to
      bacterial lipopolysaccharides (LPS) of chemotypes Rb-Re, but not to lipid A. 2. 2
      Keto-3-deoxy octonate (KDO) was the most effective sugar so far tested for
      inhibition of the hemagglutinating activity of Periplaneta lectin. 3. Periplaneta
      lectin was suggested to participate in the clearance of bacteria injected into
      the abdominal cavity of the cockroach.

PMID- 8281763
TI  - Creatinine assay by the fuller's earth procedure or by enzymatic determination is
      adequate for urine but not plasma of mice.
AB  - 1. Mouse plasma creatinine measured by fuller's earth (15.1 +/- 0.5(41) microM,
      mean +/- SE) exceeded the same pools read by HPLC [7.5 +/- 0.2(41); P < 0.001].
      2. For mouse urine, the fuller's earth method (3.26 +/- 0.21 mM) slightly
      exceeded the HPLC method (2.65 +/- 0.18; P < 0.001) with good correlation (r =
      0.915, P < 0.001). 3. An enzymatic method (creatinine PAP, Boehringer-Mannheim
      Diagnostics) for plasma creatinine (5.2 +/- 0.3 microM) was equivalent to HPLC
      (6.1 +/- 0.1, NS) but with poor correlation (r = 0.23, NS). 4. Creatinine in the
      urine agreed closely between HPLC (2.84 +/- 0.12 mM) and the enzymatic procedure
      (2.95 +/- 0.17, NS) with good correlation (r = 0.845, P < 0.001).

PMID- 8281764
TI  - The expression of matrix metalloproteinases and their inhibitors by pig synovial
      cells and their regulation by combinations of cytokines and growth factors.
AB  - 1. Pig synovial fibroblasts in culture were studied to determine if they were an
      easily reproducible model system for studying the actions of cytokines and growth
      factors on human synovial cells. The biochemical analyses were conducted by
      activity assays, enzymography and Northern blot. 2. Human recombinant interleukin
      1 alpha, basic fibroblast growth factor and transforming growth factor-beta 1
      were studied in combinations because of their known involvement in controlling
      tissue remodelling. 3. The response of pig fibroblasts to these agents, in terms
      of the expression of matrix metalloproteinases (collagenase, gelatinase and
      stromelysin) and their inhibitors (TIMPs), show that they behave similarly enough
      to human cells for use when supplies of human primary cells are unavailable.

PMID- 8281765
TI  - Evidence for two isoforms of carbonic anhydrase II in the leech (Hirudo
      medicinalis) central nervous system.
AB  - 1. We dissected, homogenized and prepared ganglia and connectives from the
      central nervous system of medicinal leeches for SDS gel electrophoresis. The
      isolated proteins were transferred to nitrocellulose and incubated with affinity
      column-purified antibodies. 2. The immunoblots showed a strong positive reaction
      of a bovine carbonic anhydrase standard at a molecular weight of 29 kDa, and a
      distinct double-bond at the same molecular weight in the analyzed material. 3. We
      demonstrated with rat antibodies that carbonic anhydrase II is detectable in the
      leech central nervous system as the main isoenzyme. 4. The biochemical knowledge
      of carbonic anhydrase reported here agrees well with the immunocytochemical
      locations, thus affirming the validity of specific staining.

PMID- 8281766
TI  - Selective modification of tryptophan-150 in ovine placental lactogen.
AB  - 1. Ovine placental lactogen was modified by reaction with o-nitrophenylsulfenyl
      chloride. Fluorescence measurements indicated that one of the two tryptophan
      residues of the molecule had reacted. Besides, there was some reagent not
      covalently bound. 2. The reagent was covalently bound to Trp-150. No evidence of
      modification of Trp-90 was found. 3. Binding capacity to lactogenic as well as
      somatogenic receptors was diminished but not abolished upon modification,
      indicating that absolute molecular integrity of Trp-150 is not required for
      binding. 4. This behavior is similar to that of the tryptophan residues of ovine
      prolactin.

PMID- 8281767
TI  - Genetic variability in South African blue wildebeest (Connochaetes oaurinus).
AB  - 1. We use protein gel-electrophoresis to investigate genetic heterogeneity at 33
      protein coding loci in a total of 46 blue wildebeest (C. taurinus) kept under
      different management regimes. 2. Average heterozygosity ranged from 2.14 to 4.3%
      and within-population differences accounted for 97.2% of total relative gene
      diversity. 3. Comparatively little divergence was found between animals sampled
      from populations with very diverse population sizes and management histories,
      with the largest genetic distance estimated between any two populations being
      only 0.0021. 4. We discuss our results with particular emphasis on the influence
      of management history on genetic diversity and divergence in C. taurinus.

PMID- 8281768
TI  - [Case study reports No. 23 (Society for the Study of Scientific Nursing)].

PMID- 8281769
TI  - [To translate workings of nursing into ward structure].

PMID- 8281770
TI  - [Kenji Miyazawa; his illness and thoughts on every-day life. Interview by Setsuko
      Sueki].

PMID- 8281771
TI  - [Searching for logic of children's recognition].

PMID- 8281772
TI  - [Beginning course of English medical terminology based on analytical methods].

PMID- 8281773
TI  - [What is psychiatry?].

PMID- 8281774
TI  - [The world of Hildegard von Bingen].

PMID- 8281775
TI  - [A trial in educational development of the general clinical nursing theory].

PMID- 8281776
TI  - [Asking about 'nursing and medicine'].

PMID- 8281777
TI  - The role of vehicles in diagnostic patch testing. A reappraisal.
AB  - The correct selection of vehicles for patch testing is crucial in the evaluation
      of suspected allergic contact dermatitis. We reviewed the literature by using
      Grateful Med software for the years 1966-1992, utilizing the subjects "vehicles"
      and "allergic contact dermatitis" or "patch tests". Vehicles can influence
      bioavailability of the chemicals and subsequently percutaneous absorption or
      interaction with allergens. There are methodological problems in interpreting
      studies, such as sample size, percutaneous absorption and clinical aspects. Our
      judgement, partially validated by the literature, suggested that improved
      delivery systems (such as via vehicles) might significantly increase
      optimization, reliability and reproducibility of patch tests.

PMID- 8281778
TI  - Centella asiatica (Indian pennywort), an effective therapeutic but a weak
      sensitizer.
AB  - The sensitizing capacity of Centella asiatica (raw extract) and its triterpenic
      constituents asiaticoside, asiatic acid and madecassic acid has been studied in
      guinea pigs. The extract itself as well as the 3 acids were found to be very weak
      sensitizers. Centella asiatica extract is used effectively in the treatment of
      keloids, leg ulcers, phlebitis, slow-healing wounds, leprosy, surgical lesions,
      striae distensae and cellulitis. Although applied frequently to damaged skin, the
      risk of acquiring contact sensitivity to this plant or its constituents is low.

PMID- 8281779
TI  - Concentration threshold of non-occluded nickel exposure in nickel-sensitive
      individuals and controls with and without surfactant.
AB  - Most cases of primary nickel sensitization are caused by occluded exposure to
      nickel released from earrings, buttons, etc. Nickel-sensitive females are both
      domestically and occupationally exposed to trace amounts of nickel. The present
      study was designed to define the minimum eliciting threshold concentration of
      nickel exposure in previously nickel-sensitized individuals, after open
      application on normal forearm skin with and without surfactant. A dilution series
      of NiCl2, ranging from 0.1 to 4000 ppm nickel with and without 4% sodium lauryl
      sulfate, was applied to healthy volar forearm skin. None reacted with definite
      allergic reactions to 100 ppm and below. Follicular reactions were seen in the
      concentration range from 0.1-100 ppm in a few patients and 1 healthy control. The
      results are discussed in relation to consumer products containing 1-10 ppm
      nickel.

PMID- 8281780
TI  - A study of the relationship between susceptibility to skin stinging and skin
      irritation.
AB  - In an evaluation of the safety of new chemicals, of products containing them, or
      of novel formulations of existing chemicals which may come into contact with the
      skin, it is important to incorporate an assessment of specially susceptible sub
      populations. Such a group is represented by those who are more likely to
      experience sensory effects such as stinging. Since these individuals are easily
      and rapidly identifiable, we investigated whether they represented a group who
      were also more susceptible to the effects of an irritant. The primary purpose was
      to discover whether 'stingers' might represent an easily and rapidly identifiable
      sub-population with a more generally increased tendency to give skin responses.
      The response to a 0.3% sodium dodecyl sulphate patch test was assessed in a group
      of 25 'stingers' and compared to the response in 25 'non-stingers'. There was no
      difference in either the pattern or strength of the irritant response assessed by
      subjective erythema and dryness scores. Thus the data suggest that there is no
      correlation between the susceptibility of an individual to a skin stinging
      response and an irritation reaction.

PMID- 8281781
TI  - Contact allergy due to colophony (VIII). The sensitizing potency of commercial
      products: an investigation of French and German modified-colophony derivatives.
AB  - The sensitizing capacity of 7 commercial modified-colophony products of different
      origins (esters, polyterpene-modified, phenol-modified, resinate, polymerisate)
      were studied experimentally in guinea pigs by means of a modified Freund's
      complete adjuvant (FCA) method. All products showed a weak sensitizing power, but
      a moderate to strong irritant effect. Within this group, the strongest response
      was obtained with the calcium resinate. As most of these products are used
      commercially in paints and lacquers, the risk of acquiring specific
      hypersensitivity must be considered low.

PMID- 8281782
TI  - Determination of threshold UV-A elicitation dose in photopatch testing.
AB  - Photopatch testing, although widely used in the diagnosis of photosensitivity
      disorders, is not standardized. We performed this study to determine the
      threshold ultraviolet light A (UV-A) dose required to elicit photopatch test
      responses. 4 patients with previously positive tests were reexposed to the
      offending allergen, using an incremental dosage regime. Isopropyl
      dibenzoylmethane (Eusolex 8020), mexenone (benzophenone-10) and oxybenzone
      (benzophenone-3) produced positive responses at 1.0, 1.0 and 0.7 J/cm2,
      respectively. Responses to phenothiazines were deemed phototoxic. These results
      demonstrate that high doses of UV-A (e.g., 10-15 J/cm2) are unnecessary, and that
      5 J/cm2 should become the current standard.

PMID- 8281783
TI  - Compositae dermatitis in a Danish dermatology department in 1 year (II). Clinical
      features in patients with Compositae contact allergy.
AB  - During our first year of routine testing with Compositae allergens and extracts,
      contact allergy to Compositae was frequently found in eczema patients (4.5%),
      especially in middle-aged or elderly persons. Based on clinical patterns, patch
      test reactions and the long-term course of the disease, 4 groups of patients were
      recognized: (a) a small group with localized eczema; (b) another with classic
      Compositae dermatitis of exposed skin; (c) a 3rd group, the largest, with
      localized eczema that suddenly one summer turned into a widespread dermatitis;
      (d) a 4th group with a vesicular hand eczema and more-or-less widespread
      dermatitis with seasonal variation from the beginning. 65% of the patients had
      vesicular hand eczema at some time, partly reflecting the frequency of atopy
      (25%) and metal allergy (44%). 75% of the patients had contact allergy to > or =
      1 compounds besides Compositae. Thus, Compositae allergy may be primary, e.g., in
      young patients with occupational plant contact, or secondary to other contact
      allergies, perhaps as a result of increased individual susceptibility. The
      clinical patterns in the latter patients were most often a widespread dermatitis
      with summer exacerbation. The variability in the clinical picture makes routine
      patch testing with Compositae allergens recommendable.

PMID- 8281784
TI  - Skin symptoms among workers in a spice factory.
AB  - Workers in a Swedish spice factory (n = 70), and in the office (n = 23) of the
      same company, were investigated by questionnaire regarding skin symptoms. In a
      2nd part of the study, subjects reporting skin symptoms were examined and
      investigated by patch and prick testing. Skin symptoms were reported by 1/2 the
      factory workers. Pruritus and skin irritation, particularly from cinnamon powder,
      were common. Patch test reactions to cinnamic aldehyde were found in 11/25
      factory workers, but in several cases, the nature of the reactions was difficult
      to evaluate. Irritant patch test reactions were seen from powders of cardamom,
      paprika and white pepper. On prick testing, 6/25 workers reacted to cinnamic
      aldehyde. The results illustrate the difficulties of patch testing with spices
      and indicate the need for further research and validation of methods.

PMID- 8281785
TI  - Sensitization in atopic and non-atopic hairdressers with hand eczema.
AB  - To investigate the capability of atopics to be sensitized to contact allergens,
      143 hairdressers with hand eczema, who had been patch tested with the
      hairdresser's series, were studied. The 125 women and 18 men were grouped
      according to their personal atopic status. There were 45 eczematous atopics, 32
      mucous membrane atopics and 66 non-atopics. Sensitization to at least one of the
      hairdressing chemicals was found in 60% of the eczematous atopics, 53% of the
      mucous membrane atopics and 58% of the non-atopics. The commonest sensitizer in
      each group was glyceryl monothioglycolate followed by para-phenylenediamine and
      related dyes. None of the 18 men were allergic to nickel but 40% of the women
      were thus sensitized. Jewelry rather than equipment was thought to be the cause.
      No significant difference was found between the eczematous atopics, mucous
      membrane atopics and non-atopics in their capacity to be sensitized to
      hairdressing allergens or to nickel.

PMID- 8281786
TI  - Occupational dermatitis from cosmetic creams.

PMID- 8281787
TI  - Occupational contact urticaria syndrome from cefotiam hydrochloride.

PMID- 8281788
TI  - Occupational contact dermatitis from tosyl chloride in a chemist.

PMID- 8281789
TI  - Paederus dermatitis--a mimic.

PMID- 8281790
TI  - Sensitization to chloroacetamide.

PMID- 8281791
TI  - Contact allergy to nicotine from a nicotine patch.

PMID- 8281792
TI  - Generalized dermatitis due to oral ephedrine.

PMID- 8281793
TI  - Contact urticaria from acrylic acid in Fixomull tape.

PMID- 8281794
TI  - Millstone tattoo: a regional trade-related dermatosis.

PMID- 8281795
TI  - Contact dermatitis from potassium chloride.

PMID- 8281796
TI  - Allergic contact dermatitis from bufexamac cream.

PMID- 8281797
TI  - Risk of contact dermatitis from UV-A sunscreens.

PMID- 8281798
TI  - Befriending the suicidal.

PMID- 8281799
TI  - Common interest of suicide and its prevention.

PMID- 8281800
TI  - Affect and the capacity for rational choice.

PMID- 8281801
TI  - The implications of Tom's case.

PMID- 8281802
TI  - Plane crash crisis intervention: a preliminary report from the Bijlmermeer,
      Amsterdam.
AB  - Psychological adjustment following airline disasters shares many characteristics
      with adjustments following other disasters, both human and natural. On October 4,
      1992, an El Al Boeing 747-F crashed into two apartment buildings in an Amsterdam
      suburb called the Bijlmermeer (The Netherlands). This paper gives a first
      impression of some of the postdisaster reactions in the affected population. It
      also describes the crisis intervention program (Aftercare Plan Bijlmermeer),
      which will be evaluated by the Bijlmer Research Project. In the Aftercare Plan
      for the Bijlmermeer, the organization and delivery of material aid and of medical
      and mental health aid was outlined. The primary goal of crisis intervention in
      this context is symptom relief. It is important that such programs are not looked
      upon as services for the mentally ill. The authors of this article plead for a
      better interaction between intervention and research. We need studies that can
      give us a better idea of the psychological effects of disaster and the
      effectiveness of various ways of providing postdisaster services to the public.

PMID- 8281803
TI  - Psychosocial care and shelter following the Bijlmermeer air disaster.
AB  - This article describes the organization of the psychosocial aid and aftercare for
      survivors in the context of the Bijlmermeer air disaster that took place in 1992
      in Amsterdam, The Netherlands. It is based on an examination of the relevant city
      documents and media coverage, and on interviews with city officials and disaster
      workers. The aid operation was complicated by the fact that the disaster struck a
      socially vulnerable multicultural community. The experiences illustrate the
      difficulties involved in coordinating the psychosocial care and aftercare
      provided by different agencies, and suggest a need for ample planning and
      training in this respect. In addition, they point to the importance of tailoring
      interventions to survivors' specific needs, careful registration of survivors and
      helpers, and limitation of the number of shelters and the distance between them.
      Finally, a two-edged strategy for dealing with the news media is advocated.
      Survivors should be maximally protected, but at the same time the press must be
      regularly and appropriately briefed, in order to use their potential for
      disseminating information to the survivors and the public.

PMID- 8281804
TI  - The regional variation of suicide and homicide in the USA and Taiwan.
AB  - This study shows that the social correlates of suicide rates in the USA and
      Taiwan are quite different, and that Durkheim's theory of suicide does not appear
      to be valid in Taiwan. By contrast, homicide rates in both nations do share some
      common social correlates, including divorce rates and crime rates.

PMID- 8281805
TI  - The relationship between sexual abuse and female suicidal behavior.
AB  - This study investigated the relationship between suicide attempts and a history
      of sexual abuse. In a sample of 158 female suicide attempters aged 20 years or
      older, 50% of the subjects reported having been sexually abused at some time.
      Sexually abused suicide attempters had shown more suicidal behavior in the past
      than their non-sexually abused counterparts (even though they were significantly
      younger), and were characterized by a more severe problem history. In the past,
      as well as shortly after the index attempt, they had experienced more serious
      problems in their relationships with significant others, with sexuality, and with
      self-fulfillment. At follow-up 1 year later, significantly more sexually abused
      women had attempted suicide during the intervening period than the women without
      a history of sexual abuse, and they also had more serious sexual problems. It is
      concluded that within a group of female suicide attempters, those with a history
      of sexual abuse are disproportionately vulnerable to repeated suicidal behavior.

PMID- 8281807
TI  - Stengel Research Award 1993.

PMID- 8281806
TI  - Prevention or preventability. Stengel Award Recipient Lecture.

PMID- 8281808
TI  - No-suicide decisions and suicide contracts in therapy.

PMID- 8281809
TI  - The clinical rationale for S-phase radiosensitization in human tumors.
AB  - Nonhypoxic cell radiosensitizers, principally the halogenated pyrimidines and
      hydroxyurea, have been studied in the laboratory and clinical setting for more
      than 30 years. Early clinical experience in the 1960s and 1970s with the
      thymidine analogs 5-bromodeoxyuridine (BUdR) and 5-iododeoxyuridine (IUdR) was
      disappointing because normal tissue toxicity eliminated any potential for
      therapeutic gain. Inadequate delivery systems for intravenous and intraarterial
      infusions also contributed to the decline of this strategy. More recently,
      laboratory investigations have revealed further information regarding the
      mechanism of IUdR/BUdR radiosensitization. This knowledge provided a rationale
      for the sequence and timing of drug and radiation exposure, which could be both
      effective and tolerable. Advancing technology also provided safer infusion
      devices, and a resurgence in clinical trials combining IUdR or BUdR and radiation
      resulted. Current laboratory studies are now providing data on tumor cell
      kinetics, which is being applied to ongoing clinical trials. Fluoropyrimidines,
      principally 5-fluorouracil (5-FU), were also used in early clinical trials and
      unlike IUdR/BUdR were found to have significant activity as single agents against
      a variety of tumor types. The clinical integration of 5-FU and radiation occurred
      more slowly, but recent trials have demonstrated a therapeutic gain. Improved
      rates of local control and survival with combined 5-FU and radiation versus
      radiation alone have now been demonstrated in patients with rectal, esophageal,
      and anal carcinomas. However, the mechanism of interaction between the
      fluoropyrimidines and radiation remains uncertain and continues to be
      investigated with the hope of improved clinical outcome. As the cellular pathways
      influenced by the halogenated pyrimidines have been defined, the potential for
      biochemical modulation of these agents has been recognized. Leucovorin, the most
      commonly applied modulator, has been shown to enhance the activity of 5-FU in
      patients with metastatic colorectal carcinoma. These studies serve as an example
      for current trials that use biochemical modulators of IUdR, BUdR, and 5-FU as
      radiosensitizers. Hydroxyurea, currently used in the treatment of chronic
      leukemia, has also been considered a radiosensitizer. As with IUdR/BUdR, the
      clinical trials have often been inconclusive and interest in this radiosensitizer
      has waned. A poor understanding of the mechanism of action and tumor cell/normal
      tissue kinetics may be responsible for the lack of overall success with this
      strategy. Current investigations of cell kinetics in humans and potential
      mechanisms of hydroxyurea action could provide information critical to future
      trials of hydroxyurea radiosensitization.

PMID- 8281810
TI  - The unborn surgical patient.

PMID- 8281811
TI  - [50 years German surgery--the path to specialism. Symposium on the occasion of
      the 70th birthday of the president of the Society of German Surgeons Prof. Dr.
      Karl Hempel. Opening remarks].

PMID- 8281812
TI  - [Vascular surgery].

PMID- 8281813
TI  - [Thoracic surgery].

PMID- 8281814
TI  - [Heart surgery].

PMID- 8281815
TI  - [Visceral surgery].

PMID- 8281816
TI  - [Plastic surgery].

PMID- 8281817
TI  - [Trauma surgery].

PMID- 8281818
TI  - [Choice of diagnostic procedures in blunt abdominal trauma].

PMID- 8281819
TI  - [Sonography of blunt abdominal trauma within the scope of pediatric polytrauma].

PMID- 8281820
TI  - [Value of various techniques in liver rupture].

PMID- 8281821
TI  - [Principles of spleen preservation in blunt abdominal trauma].

PMID- 8281822
TI  - [Trauma of the bilio-pancreatic compartment].

PMID- 8281823
TI  - [Visceral-urologic injuries in pelvic trauma].

PMID- 8281824
TI  - [General classification of distal radius fractures and treatment of extra
      articular distal radius fractures (Type A2 and A3)].

PMID- 8281825
TI  - [Treatment of simple intra-articular radius fractures (type B1-B3)].

PMID- 8281826
TI  - [Treatment of distal multi-fragment joint fractures of the radius. Indications,
      technique and results].

PMID- 8281827
TI  - [Diagnosis and treatment of concomitant injuries and sequelae of distal radius
      fractures].

PMID- 8281828
TI  - [Current status of experimental transplantation of allogeneic extremities].
AB  - The experimental and clinical progress in the field of immunosuppression,
      microsurgical replantation and macro-replantation provides a basis for the
      allotransplantation of whole limbs or anatomical segments. Possible indications
      would be clinically: Posttraumatic and tumor-induced defects, as well as
      congenital and infectious mutilations. Specific immunological problems of
      rejection under different immunosuppressive regimens and future methods for the
      induction of immune tolerance are discussed.

PMID- 8281829
TI  - [Unreamed intramedullary nail or external fixator in complicated tibial fracture?
      A comparative analysis].
AB  - Sixty-seven fractures of the tibial shaft with concomitant soft tissue injury
      were managed at the "Bergmannsheil" Bochum, University Clinic between May 1, 1991
      and March 31, 1993. 33 fractures underwent unreamed nailing whereas 34 fractures
      were stabilized with external skeletal fixation. There were 20 closed fractures
      with soft tissue compromise (13 types GII and 7 types GIII (Oestern/Tscherne
      classification)) and 25 compound fractures (8 grade I, 12 grade II and 27 grade
      III (Gustilo-Anderson classification)). The grade III open fractures were
      subdivided by the Gustilo-Mendoza-Williams classification (13 types IIIA, 10
      types IIIB and 4 types IIIC). Sixty-five fractures have healed (1 amputation type
      IIIC, 1 patient died). The mean time to union was 28 weeks in the fixator group
      and 23.5 weeks in the unreamed nail group (statistically not significant, p <
      0.095). Also the infection rate (1 case in each group), the fasciotomies due to
      compartment syndrome, the number of bone grafts, the number of device change and
      mesh grafts was not statistically significant in both groups. Only the number of
      performed flaps for wound coverage was statistically significant higher in the
      fixator group (p < 0.05). In the unreamed nailing population, breakage of the
      locking bolts occurred in 4 cases. In 3 cases secondary reamed nailing was
      necessary (2 delayed unions, 1 avulsion of distal bolts). Two fractures underwent
      dynamization by removal of the distal locking bolts 6 weeks post initial static
      nailing. The unreamed nail is a versatile implant for tibial shaft fractures with
      closed and open soft tissue compromise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281830
TI  - [Subsequent fractures of the femur shaft. Classification, etiology and treatment-
      a retrospective study].
AB  - Refractures of the femur frequently occur after open fractures or following an
      infection. There has to be distinguished between aseptic and septic refractures.
      Both forms have in common dystrophy as a favoring factor at the time point of
      refracture. Traumatizing means of osteosynthesis, missing soft tissue protection
      and lack of medial support after internal fixation are the main factors
      concerning the development of refractures. In case of aseptic refractures of the
      femur we propose intramedullary nailing if possible independent of the method of
      primary osteosynthesis. In case of septic refractures infect repair comes first.
      Besides internal fixation, autogenous cancellous or cortico-cancellous bone graft
      and plastic soft tissue repair are of most importance. We propose the following
      procedure for fractures of the femur with severe soft tissue damage: Primary
      fixation with fixateur externe, after soft tissue repair electively
      intramedullary nailing or internal fixation, in case of missing medial support
      combined with autogenous cancellous or cortico-cancellous bone graft. This
      procedure showed a rate of 0.9% of refractures after primary operative treatment
      of 2073 fractures of the femur at the Berufsgenossenschaftliche Unfallklinik
      Tubingen.

PMID- 8281831
TI  - [Plaster-free, early functional after-care of surgically managed Achilles tendon
      rupture].
AB  - The widely used treatment of Achilles tendon rupture by operation and
      postoperative plaster is more and more controversially discussed. The
      disadvantages of plasters with thrombosis and joint stiffness and recent results
      about tendon healing makes it worth while to illucinate an immediate functional
      physiotherapy. Our study consists of two groups of patients who were operated for
      tendon rupture. Postoperative one group (n = 24) was treated with a plaster for
      six weeks. The second group (n = 17) was immediately treated by physiotherapy
      without any immobilisation. After a mean time interval of 19.8 months the joint
      movement and tendon flexibility was evaluated. Furthermore soft tissue ultrasound
      was performed to measure the tendon tissue density and gliding movement. Our data
      showed that 1. Early functional treatment resulted in minor problems (35%) than
      immobilisation (46%). 2. Plaster-free treated patients had higher tendon density
      values (grade II 41%, grade III 47%, grade IV 12%), which depicts a higher
      tensile strength than the comparable group (grade II 29%, grade III 58%, grade IV
      13%). 3. Plaster-free treated patients showed significant lesser adhesion
      formation to the Achilles tendon (grade I 29%, grade II 53%, grade III 18%) than
      immobilisation (grade I 4%, grade II 59%, grade III 37%).

PMID- 8281832
TI  - [Child abuse--a surgical analysis].
AB  - Non-accidental injuries are frequently treated by surgeons without the real
      reason behind the trauma being identified: The differential diagnosis of child
      abuse would not be considered in this circumstance. This report gives hints as to
      the different aspects of this complex type of injury. With our case unusual
      (atypical) injury patterns have been shown and the diagnostic and therapeutic
      procedures with child abuse explained from a surgical point of view. It is of
      central importance to check, whether the trauma history according to the
      accompanying adults for the actual surgical type of injury is plausible.
      Incongruencies here must lead to search for further signs of trauma or its
      residues. When treating these children the surgeon is therefore in a key position
      especially to prevent future abuse, bearing in mind the special relevance of its
      striking high recidivation frequency.

PMID- 8281833
TI  - [Equestrian accidents in children].
AB  - In a retrospective study we reviewed 262 horse riding related injuries in
      children younger than 16 which were treated between 1975 and 1989 at the Section
      of Traumatology in the Department of Surgery, University Hospital Homburg/Saar.
      In 155 of these accidents, detailed information was gained via a questionnaire.
      The typical patient profile was that of young female equestrians with little
      experience and little weekly riding practice, without practicing falling
      exercises and warming up often using different horses. At the time of the
      accident only 59% were wearing a head protection. Most accidents happened in the
      summer months in the afternoon during leisure riding on a large familiar horse in
      the riding hall. Apart from the typical accidents like falling of the horse
      (64.9%) and falling with the horse (5.7%) accidents in handling the horse were of
      special significance: Kick by horse's hoof (11.8%), being stepped by horse
      (3.8%), horsebite (7.3%) and injuries of horse's bridle had their own pattern of
      injuries. Injuries of the distal parts of the upper extremity are preeminent in
      falling of the horse, whilst in falling with the horse head injuries and shoulder
      injuries are preeminent. Remarkably often injuries of kick by horse's hoof were
      causing sometimes even dangerous head injuries (41.6%). Overall in horse riding
      related injuries in childhood superficial soft tissue injuries (48.6%) and
      fractures (30.6%) were predominant. Fractures of the clavicle which are well
      known as a riding injury proved to be typical for a fall with the horse, whilst a
      fractured vertebra was only seen once amongst the 262 children treated. The
      severity of the injuries was lower than expected: In 85.1% of all the injuries
      only one body region was injured, 90.1% could be assigned to an injury severity
      score (ISS) of 1-3. Ponyriders had less severe injuries than riders of large
      horses. One fatal accident happened in handling a horse, in these situations
      preventive measures are often disregard. Active (better education, warming up,
      falling practice) an passive (head protection!) safety measurements are
      recommended for prevention of injuries in young riders in particular.

PMID- 8281834
TI  - [Compensation behavior after fractures of the thoracic and lumbar spine in
      children and adolescents].
AB  - Spinal column trauma with a fracture of the breast and lumbar spine is with 2-3%
      relatively uncommon in the pediatric patient population (from birth-16 years). In
      a review of 22 patients (7-15 years old) treated between 1978-1988 the individual
      management of treatment is reported. The goal of our study was to describe the
      absolute indications for the operative treatment and the difference between
      conservative and operative procedure depending on the age of the patient. The
      follow-up study after an average of 7 years and 8 months demonstrated an
      improvement of the neurological status (neurological status of Frankel) of 8
      patients and a spontaneous correction of kyphotic angle from 21 degrees after
      treatment to 3 degrees. THE CONCLUSION: The treatment must be individual and
      depends on the age of the patient.

PMID- 8281835
TI  - [Reconstructive secondary interventions in scalp defects].
AB  - Scalp defects in combination with exposure of the skull require early
      debridements and immediate soft tissue coverage by local flaps or free tissue
      transfer. Tactical and technical treatment rationale options are discussed, which
      are necessary to achieve patient specific reconstructive procedures.

PMID- 8281836
TI  - [Treatment strategy in explosion and gunshot injuries of the upper extremity].
AB  - Explosion and gunshot injuries represent a challenging problem with regard to
      preserve optimal hand function. These wounds exhibit a spectrum of complexity and
      mostly include extensive soft tissue trauma complicated by burns, foreign bodies,
      fractures and concomitant trauma. To gain maximal restoration of hand function
      the use of microsurgical technique, grafting of nerves, vessels and soft tissue
      as an acute free flap to cover a large defect immediately is necessary. The
      experience in treatment of 38 cases of blast and gunshot injuries of the hand are
      reported. The results are discussed in relation to literature, complication,
      indication and technique.

PMID- 8281837
TI  - [Free vascularized bone transplantation].
AB  - A report is presented on 4 years of experience with free vascularized bone
      transplants for extremity preservation and the postoperative management developed
      in this connection. The successful results so far were achieved not least by
      virtue of a strict unified postoperative treatment scheme extending from direct
      postoperative blood-flow monitoring through the raising of a skin flap and
      angiographic control of anastomosis patency to immobilization/mobilization and
      orthotic management. Thus far, 33 patients have been treated with free
      vascularized bone transplants (20 fibula, 13 iliac crest grafts).

PMID- 8281838
TI  - [Synovial hemangioma of the knee joint--a rare cause of recurrent hemarthrosis].
AB  - In the differential diagnosis of bloody knee joint effusions synovial haemangioma
      as a rare cause has to be considered. Especially suspicious are long durations of
      disease with recurrent atraumatic blood-stained joint effusions and repeated
      episodes of painful limitation of motion, laboratory and radiographic findings
      often being normal. On the one hand arthroscopy can prove the diagnosis by
      obtaining an ample biopsy specimen, on the other hand it facilitates the healing
      of the lesion at the same time by radical removal of the tumour.

PMID- 8281839
TI  - [Intra-abdominal migration of a Kirschner wire from the femoral neck].
AB  - A epiphysiolysis capitis femoris in a child was treated bei Kirschner-wire
      fixation. Postoperatively one of these wires broke and presumably migrated
      through the acetabulum intraperitoneally into the true pelvis. The Kirschner-wire
      fragment was removed by laparotomy. We discuss the technique of application of
      Kirschner-wires and complications of the procedure, in particular migration and
      dislocation.

PMID- 8281840
TI  - [Isolated proximal fibula fracture in Marfan syndrome].
AB  - An isolated fracture of the proximal fibular shaft without associated tibial or
      ankle injury and without resulting from direct violence is extremely rare. This
      report presents a case of an unusual isolated proximal fibular fracture (stress
      fracture) in a female tennis-player with Marfan-syndrome. The literature is
      reviewed and diagnosis, treatment and etiology are discussed.

PMID- 8281841
TI  - [Ambulatory prevention of thrombosis in plaster immobilization of the lower
      extremity].

PMID- 8281842
TI  - Pruritus associated with cholestasis. A review of pathogenesis and management.

PMID- 8281843
TI  - Increased abdominal pain during final examinations.
AB  - Anecdotes and animal experiments alike suggest that physiological and
      psychological stress can profoundly alter gastrointestinal function. However, few
      studies have examined, in humans, real-world stress to see if free-living persons
      exhibit gut alterations similar to those produced in the laboratory. To
      investigate this possibility, we studied 16 medical and premedical students
      during final written examinations. As compared to a control day, the examination
      created a classic stress response: elevated serum cortisol (16 +/- 1 to 21 +/- 3
      micrograms/dl; P < 0.05), ACTH (31 +/- 1 to 33 +/- 1 pg/ml; P < 0.05), heart rate
      (72 +/- 3 to 79 +/- 3 beats/min; P < 0.05), arterial blood pressure (systolic
      pressure 106 +/- 2 to 120 +/- 2 torr; P < 0.05; diastolic pressure 72 +/- 2 to 77
      +/- 1 torr; P < 0.05), and subjective anxiety (raw score 28 +/- 2 to 47 +/- 3; P
      < 0.0001). In contrast, subjects displayed identical orocecal liquid transit time
      (of 0.36 g/kg lactulose in a 240-ml, 250-kcal liquid meal) under control (103 +/-
      8 min) and examination conditions (106 +/- 8 min; P = NS). Mean subjective
      reports of gas, diarrhea, and borborygmi were unchanged on the day of the
      experiment, although the examination did increase reported abdominal pain (from
      0.5 +/- 0.4 to 2.1 +/- 0.5 on a 0-5 analog scale; P < 0.05). We conclude that
      examination stress in humans can increase gastrointestinal symptoms without
      altering orocecal transit.

PMID- 8281844
TI  - Inter- and intrasubject variability of solid and liquid gastric emptying
      parameters. A scintigraphic study in healthy subjects and diabetic patients.
AB  - This study was performed to assess: (1) the inter- and intrasubject variability
      of gastric emptying measurements by a scintigraphic method in 12 healthy subjects
      and 14 diabetic patients, and (2) the reproducibility of diagnosis of either the
      presence or absence of gastroparesis. To address this issue, radiolabeled solid
      liquid meals were ingested by all subjects on two separate days. High
      intersubject variability of gastric emptying measurements was shown in both
      populations. Intrasubject variability was higher in diabetic patients than in
      healthy subjects. However, there was no significant difference between the means
      of any parameters obtained on two separate days. The reproducibility of the
      diagnosis of gastroparesis was excellent for all parameters; the solid half
      emptying time was the most reproducible parameter (92% in healthy subjects and
      93% in diabetic patients). The means +/- SD of the difference between the two
      separate days' half emptying time results were -10.6 +/- 41.3 min for solids and 
      4.8 +/- 36.6 min for liquids and were not statistically different from zero. Only
      one difference between the half emptying time results on two separate days was
      not in the 95% confidence interval for both solids and liquids; however, this
      result came from a diabetic patient with obvious gastroparesis on both days.
      Thus: (1) in spite of high inter- and intrasubject variability, the scintigraphic
      method of measuring gastric emptying is highly reproducible for the diagnosis of
      gastroparesis; (2) reproducibility is better in healthy subjects than in diabetic
      patients; and (3) the knowledge of intrasubject variability allows assessment of
      the required sample sizes for pharmacological studies using prokinetic
      medications.

PMID- 8281845
TI  - Autofluorescence in onset of gastric mucosal injury induced by hemorrhagic shock
      in rats.
AB  - In an attempt to clarify whether gastric mucosal autofluorescence can help us to
      recognize gastric lesions at the onset of their formation, we investigated the
      fluorescence generated from the gastric mucosa of rats under ischemia-reperfusion
      stress. Red-colored fluorescence appeared and began to increase within 5 min
      after reperfusion. Such an increase in fluorescence did not occur in the gastric
      mucosa under prolonged ischemia without reperfusion. The epifluorescence
      microscopy of mucosal cryosections revealed that fluorescence was present even
      when only superficial mucosal damage occurred. Spectrofluorometric and high
      performance liquid chromatographic analysis of the fluorescent mucosa extract
      identified the fluorescent substances as porphyrins. These findings suggested
      that fluorescent porphyrins are generated in the mucosal layer during the
      introductory phase of mucosal lesion formation induced by ischemia-reperfusion
      stress.

PMID- 8281846
TI  - Erythromycin accelerates solid emptying at the expense of gastric sieving.
AB  - Erythromycin accelerates gastric emptying by inducing antral contractions similar
      to phase III of interdigestive MMC. These powerful contractions are capable of
      forcing coin-sized indigestibles out of the stomach. In contrast, fed motility is
      associated with submaximal contractions that fragment (trituration) and propel
      solids while retaining large (> 0.5 mm) pieces for further size reduction
      (gastric sieving). In this study, using dogs with duodenal fistulas, we tested
      the hypothesis that erythromycin-induced acceleration of gastric emptying
      resulted in the passage of inadequately triturated (> 0.05 mm) chunks of solids
      into the duodenum. We found that gastric emptying was accelerated by erythromycin
      (vs 0.15 M NaCl control, P < 0.05). However, the percentage of chyme collected in
      the > 0.5-mm fraction was much greater (P < 0.01) in the erythromycin-treated
      experiments (63 +/- 9%) than the controls (7 +/- 1%). Correspondingly, while a
      fine gruel was passed during controls, under erythromycin infusion, most of the
      solids were emptied as large chunks virtually unchanged from the swallowed
      pieces. We conclude that erythromycin accelerates gastric emptying at the expense
      of gastric sieving.

PMID- 8281847
TI  - Effects of oral erythromycin on esophageal pH and pressure profiles in patients
      with gastroesophageal reflux disease.
AB  - Erythromycin, a possible motilin agonist, is a potent gastrokinetic agent that
      may increase the lower esophageal sphincter pressure. Therefore, we assessed the
      effects of erythromycin in two dosages (250 and 500 mg per os four times a day)
      on esophageal pH and pressure profiles in reflux patients using prolonged
      ambulatory monitoring systems. Studies were blinded, placebo-controlled with
      randomized crossover design. Patients took each drug for three days prior to
      studies, with erythromycin serum levels obtained the day of esophageal studies.
      Erythromycin 250 mg four times a day had no effect on esophageal contraction
      pressures or peristalsis during the day or meal periods. In the supine position,
      however, erythromycin significantly (P = 0.012) decreased esophageal contraction
      velocity and showed a strong trend (P = 0.059) towards increasing the percentage
      of peristaltic waves. Despite these potentially beneficial effects on esophageal
      clearance, no significant difference in acid exposure times during 24-hr pH
      studies were observed between placebo and low-dose erythromycin. High-dose
      erythromycin (500 mg four times a day) was associated with drug levels in the
      typical antibiotic efficacy range (normal 1-3 micrograms/ml; patients 1.7-7.0
      micrograms/ml), but, here again, there was no significant difference in all acid
      reflux parameters between placebo and erythromycin phases. Therefore, "standard"
      doses of erythromycin have no important clinical effects on esophageal pressures
      or acid reflux parameters.

PMID- 8281848
TI  - Neutrophil-mediated injury to gastric mucosal surface cells.
AB  - Neutrophils (PMNs) have been implicated in the pathogenesis of gastritis. This
      study evaluates the magnitude and mode of PMN-mediated damage to gastric mucosal
      surface cells (GSC) in a system independent of vascular and neural factors.
      Rabbit GSC were freshly isolated and preloaded with 51Cr. GSC were then incubated
      for 1 hr or 4 hr with freshly isolated human PMNs at varying effector-to-target
      cell ratios. Injury to GSC was assessed as percent specific 51Cr released and by
      electron microscopy. We found minimal GSC injury using nonactivated PMNs.
      Incubation with PMNs activated with formylmethionyl-leucyl-phenylalanine (FMLP),
      however, resulted in significant GSC injury at the 20:1 PMN/GSC ratio, 33.2 +/-
      1.8% 51Cr release (P < 0.001 compared to nonactivated PMNs). Electron microscopy
      revealed well-preserved gastric surface cells after exposure to nonstimulated
      PMNs. GSC exposed to activated PMNs (20:1 PMN/GSC ratio) were severely injured.
      Proteinase inhibitors and dimethylsulfoxide failed to diminish PMN-mediated GSC
      injury. Conversely, superoxide dismutase (SOD) inhibited GSC injury by more than
      50% (P < 0.001). In addition, glutathione peroxidase inhibited injury by 84% (P <
      0.001). These data suggest that neutrophil-mediated injury to gastric surface
      cells in vitro involves superoxide anion and hypochlorous acid and not neutral
      trypsinlike proteinases or hydroxyl radicals.

PMID- 8281849
TI  - Superoxide inhibition following different stimuli of respiratory burst and
      metabolism of aminosalicylates in neutrophils.
AB  - Reactive oxygen species such as superoxide radicals have been proposed to play an
      important role in the pathogenesis of inflammatory bowel disease. Some of the
      antiinflammatory actions of aminosalicylates have been ascribed to their
      capability to scavenge superoxide radicals directly or to inhibit its production
      in stimulated neutrophils. However, as a controversy still exists with regard to
      the precise mechanisms of inhibition and the metabolism within inflammatory
      cells, we compared scavenger properties of 5-aminosalicylic acid, 4
      aminosalicylic acid, N-acetyl aminosalicylic acid, olsalazine, and benzalazine in
      systems with defined superoxide radical generation such as the dimethyl sulfoxide
      NaOH and the potassium superoxide system. We also studied possible inhibition of
      the superoxide production following different stimuli of the respiratory burst in
      neutrophils and investigated the uptake and potential metabolism (N-acetylation)
      of 5-aminosalicylic acid in lipopolysaccharide-primed and resting neutrophils. We
      found that 5-aminosalicylic acid and 4-aminosalicylic acid had defined scavenger
      properties in the dimethyl sulfoxide-NaOH or potassium superoxide systems,
      respectively, whereas compounds with a modified aminophenolic structure had no
      effects. At the cellular level, 5-aminosalicylic acid inhibited phorbol myristate
      acetate (100 ng/ml)-activated superoxide generation to 82.3 +/- 9.3%, the
      formylmethionyl leucyl peptide (10(-5) M) to 61.0 +/- 6.8%, and the NaF (20 mM)
      stimulated production to 32.3 +/- 3.2% (mean +/- SD, P < 0.01). The actions of
      the other drugs were less pronounced. Almost identical retention times (Rt = 11.2
      min) of 3H-labeled phorbol myristate acetate in the presence and absence of 5
      aminosalicylic acid revealed no in vitro interactions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8281850
TI  - Interleukin-1 receptor antagonist does not prevent endotoxin-induced inhibition
      of gastric acid secretion in rats.
AB  - The underlying mechanisms involved in endotoxin-induced inhibition of gastric
      acid secretion were investigated in conscious rats with pylorus ligation for 2
      hr. Intraperitoneal injection of endotoxin (0.1, 1, and 5 micrograms/rat)
      inhibited gastric acid output by 31%, 80%, and 84% respectively. Intraperitoneal
      endotoxin (1 microgram/rat) -induced inhibition of gastric acid secretion was not
      altered by pretreatment with the interleukin-1 receptor antagonist, IL-1RA,
      indomethacin, naloxone, or capsaicin. Treatments were injected peripherally at
      doses previously shown to antagonize the antisecretory effect of exogenous
      interleukin-1 beta, to inhibit prostaglandin synthesis in the stomach and brain,
      to block opiate receptors, and to alter functioning of unmyelinated afferent
      nerve fibers. These results indicate that the antisecretory effect of endotoxin
      can be expressed by factors other than interleukin-1, prostaglandins, or opioid
      peptides that do not require the integrity of capsaicin-sensitive afferent
      pathways.

PMID- 8281851
TI  - Translocation of bacteria due to direct mucosal damage caused by Gastrografin. An
      experimental study in newborn rats.
AB  - A study was carried out on 40 newborn rats to determine the effect of
      Gastrografin (a hyperosmolar solution, 1700 mosm/liter) on the gastrointestinal
      tract. All the newborns received an inoculum of Klebsiella bacteria to the
      gastrointestinal tract. Thirty received, in addition to maternal milk, a feeding
      of Gastrografin twice daily. The Gastrografin was found to cause severe and
      irreversible damage to the mucosa of the small intestine, causing the death of 24
      rats less than a week after start of the experiment. The 10 rats who received no
      Gastrografin and served as controls showed no signs of disease or damage to the
      intestinal tract. Cultures taken from the peritoneal cavity after sacrifice were
      all positive for Klebsiella in the Gastrografin group (30 rats) and negative in
      the controls (10 rats). This study has therefore demonstrated that severe damage
      to the small intestine mucosa will lower the intestinal barrier and lead to
      transmural translocation of bacteria into the peritoneal cavity.

PMID- 8281852
TI  - Variability in individual response to various doses of omeprazole. Implications
      for antiulcer therapy.
AB  - This study was carried out in order to perform a combined prospective assessment
      of the individual pharmacodynamic response and of duodenal ulcer healing in
      patients treated with three different doses of omeprazole. Ninety-nine patients
      with endoscopically proven duodenal ulcers were subdivided into three parallel
      groups of 33 cases, who were randomly assigned to receive orally at 0800 hr, in
      single blind fashion, either 10 mg, 20 mg, or 40 mg of omeprazole. All of them
      underwent continuous intragastric pH monitoring both in basal conditions and on
      the fifth day of each dose regimen; ulcer healing was then assessed
      endoscopically after four weeks of treatment. All three doses of omeprazole
      caused pH values to increase significantly (P < 0.001) over the whole 24-hr
      period. In patients treated with omeprazole 10 mg, the individual responses
      showed the highest variability: the acid inhibition, expressed in terms of time
      spent above pH 3.0, lasted for more than 16 hr in 42% of cases, for more than 8
      hr in 28%, and for less than 6 hr in 30%. In patients treated with omeprazole 20
      mg, the pharmacological response was more marked and uniform and lasted for more
      than 16 hr in 79% of cases; however, it is worth noting it lasted for less than 6
      hr in three patients (10%). In patients treated with omeprazole 40 mg, the
      individual response was excellent (more than 16 hr) in 94% of cases, and it
      lasted for less than 6 hr in only one patient (3%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8281853
TI  - Effect of proton pump inhibitor, omeprazole, on expression of rat parietal cell
      specific carbohydrate antigen, type 2 chain N-acetyllactosamine.
AB  - The effect of a proton pump inhibitor, omeprazole, on the rat gastric mucosal
      expression of carbohydrate antigens was studied. Type 2 chain N-acetyllactosamine
      was detected specifically on the apicocanalicular cell membranes of parietal
      cells. Pretreatment of rats with omeprazole profoundly suppressed the antigen
      expression, which followed the inhibition of gastric acid secretion. When
      omeprazole was discontinued, the antigen was reexpressed, which preceded the
      restoration of acid secretion. The antigen-negative tissues became antigen
      positive when they were desialylated. Gastric membrane vesicles from the normal
      and omeprazole-treated rats were antigen-positive and -negative, respectively.
      SDS-PAGE revealed that a glycoprotein with an apparent molecular weight of 64-78
      kDa carried type 2 chain N-acetyllactosamine. In the omeprazole-treated rats, the
      same molecular weight glycoprotein was positively immunostained only after
      desialylation. We concluded that: (1) the expression of type 2 chain N
      acetyllactosamine was closely correlated with gastric acid secretion, and (2) the
      inhibition of acid secretion was accompanied by the sialylation of the parietal
      cell membrane glycoprotein.

PMID- 8281854
TI  - Effect of transforming growth factor-alpha on gastric acid secretion in rats and
      monkeys.
AB  - The effect of transforming growth factor-alpha was studied in histamine
      stimulated gastric acid secretion in monkeys and in pylorus-ligated rats. In
      monkeys, transforming growth factor-alpha given intravenously in a stepwise
      manner gradually reduced gastric acid secretion. A dose of 0.1 mmol/kg induced
      about a 50% inhibition of gastric acid output, while about 100% inhibition of the
      same parameter, was observed after a dose of 1 nmol/kg. Following a single
      administration of 1 nmol/kg intravenously in monkey, the maximum inhibitory
      effect on gastric acid output was reached 60 min after the administration of the
      drug, when a 91.8% inhibition was observed. Pretreatment values were reached 210
      240 min after transforming growth factor-alpha administration. In pylorus-ligated
      rats, transforming growth factor-alpha, at doses of 9 and 18 nmol/kg produced an
      almost complete inhibition of gastric acid secretion. In this model, the ED50 was
      calculated to be 4.5 nmol/kg. Comparison with epidermal growth factor on the same
      models of gastric acid secretion showed that these two compounds have similar
      inhibitory potency. However, the effect of transforming growth factor-alpha on
      gastric acid secretion in monkeys was shorter lasting than that of epidermal
      growth factor.

PMID- 8281855
TI  - Hospital discharges resulting from esophagitis among Medicare beneficiaries.
AB  - Despite the frequent occurrence of gastroesophageal reflux disease, until now
      only very few studies have dealt with the epidemiology of this common disorder.
      The Health Care Financing Administration complies annually 10 million records of
      all hospital discharges among Medicare beneficiaries distributed throughout the
      United States. The purpose of the present study was to take advantage of this
      large data set and analyze the demographic characteristics of patients discharged
      with esophagitis, esophageal ulcer, or esophageal stricture. The hospital
      discharge rates of all three diagnoses showed an age-related rise, the rise being
      most pronounced for esophageal stricture and, less significant, esophageal ulcer.
      The marked age dependency of esophageal stricture and ulcer may reflect the time
      necessary for complications to develop. While simple esophagitis affected women
      more frequently than men, significantly more men contracted its severe forms
      involving ulcers and strictures. All forms were more common in whites than
      blacks, and living in the southern parts of the United States was associated with
      an increased risk for esophagitis and strictures. The data suggest that besides
      varying exposure to environmental risk factors, differences in the
      pathophysiology among demographically stratified groups contribute to the
      occurrence of esophagitis.

PMID- 8281856
TI  - Effect of viscosity on oropharyngeal and esophageal emptying in man.
AB  - The effect of bolus viscosity on oropharyngeal and esophageal emptying is not
      known. We investigated this question in 38 healthy volunteers by measuring the
      transit of five semisolid boluses of varying viscosities across the oropharynx
      and the esophagus with the aid of scintigraphy. The studies were performed twice
      on consecutive days. The results show that oropharyngeal and esophageal emptying
      are reliably reproduced from day to day. Esophageal emptying was inversely
      related to bolus viscosity; however, oropharyngeal emptying was not influenced by
      bolus viscosity. We conclude that bolus viscosity has significant, but selective,
      effect on oropharyngoesophageal emptying.

PMID- 8281857
TI  - Effect of graded exercise on esophageal motility and gastroesophageal reflux in
      nontrained subjects.
AB  - The effects of graded exercise on esophageal motility and gastroesophageal reflux
      were evaluated in nine nontrained subjects, using a catheter with three strain
      gauge transducers connected to a solid-state datalogger and an ambulatory
      intraesophageal pH monitor. Subjects exercised on a stationary bike at 45%, 60%,
      75%, and 90% of peak O2 uptake (VO2 max). Durations of exercise sessions and rest
      periods varied among subjects. Studies were performed after an overnight fast and
      subjects received only intravenous infusion of 5% glucose solution during the
      study. Plasma concentrations of gastrin, motilin, glucagon, pancreatic
      polypeptide (PP), and vasoactive intestinal peptide (VIP) were determined at rest
      and before and after each exercise session. The duration, amplitude, and
      frequency of esophageal contractions declined with increasing exercise intensity,
      and the differences were significant (P < or = 0.05) for all three variables at
      90% VO2 max. The number of gastroesophageal reflux episodes and the duration of
      esophageal acid exposure were significantly (P < or = 0.05) increased during
      exercise at 90% VO2 max. Plasma regulatory peptide concentrations showed no
      significant changes between rest and the various exercise sessions. Thus,
      exercise has profound effects on esophageal contractions and gastroesophageal
      reflux, which are intensity dependent. These effects were not mediated by the
      hormones measured. The results were similar to those observed in highly trained
      athletes, suggesting that the effects of exercise on esophageal function are
      similar in trained and nontrained subjects performing at similar percentages of
      VO2 max, even though the absolute levels of exercise achieved in each group are
      different.

PMID- 8281858
TI  - Correlation of 24-hr esophageal pH patterns with clinical features and endoscopy
      in gastroesophageal reflux disease.
AB  - We performed 24-hr ambulatory esophageal pH monitoring in north Indian patients
      with gastroesophageal reflux disease (GERD) and correlated it with symptom
      severity and endoscopic abnormalities. Thirty-six consecutive patients with
      symptomatic GERD and 16 healthy volunteers underwent objective grading of
      clinical symptoms and endoscopic findings. Total, supine, and upright reflux
      periods as well as frequency and duration of reflux episodes were determined from
      the 24-h pH-metry record using standard software. This was abnormal in 32
      patients, who could be categorized into upright refluxers (31.2%), supine
      refluxers (34.4%), and combined refluxers (34.4%). Supine reflux and upright
      reflux were distinct entities that did not correlate with each other (r = 0.22, P
      = NS). In upright refluxers, symptoms (P < 0.02) and endoscopic abnormalities (P
      < 0.005) were milder than in combined refluxers. Total duration of acid exposure
      correlated significantly with severity of symptoms (P < 0.001) and endoscopic
      esophagitis (P < 0.005). Patients with GERD had three distinct patterns of
      abnormal gastroesophageal reflux, with upright refluxers having milder disease
      and supine and combined refluxers having more severe disease. This may reflect
      differences in underlying mechanisms of reflux.

PMID- 8281859
TI  - Peritoneal Kaposi's sarcoma: a cause of ascites in acquired immunodeficiency
      syndrome.
AB  - The investigation of ascites in a homosexual man with acquired immunodeficiency
      syndrome and mucocutaneous Kaposi's sarcoma (KS) revealed only numerous purplish
      nodules of KS in the parietal and serosal peritoneum, observed at laparoscopy. KS
      lesions of the peritoneum, a finding not reported in the literature previously,
      was the only and likely cause of ascites in our patient. Increased red cells and
      high serum-ascites albumin gradient in a patient with acquired immunodeficiency
      syndrome should suggest the possibility of peritoneal KS as a cause of ascites.

PMID- 8281860
TI  - Simple hepatic cysts. First case report of percutaneous drainage and sclerosis
      with doxycycline, with a review of literature.

PMID- 8281861
TI  - Deceptive epistaxis during gastroscopy.

PMID- 8281862
TI  - High interleukin-6 concentrations in hepatic ascites.

PMID- 8281863
TI  - Genotype of hepatitis C virus in fulminant hepatitis C.

PMID- 8281864
TI  - Phosphorus-31 nuclear magnetic resonance in vivo spectroscopy of human liver
      during hepatitis A virus infection.
AB  - To evaluate the changes in hepatocellular phospholipid metabolism during
      hepatitis virus infection, 26 patients with acute viral hepatitis A were studied
      by means of phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. The
      spectroscopy of liver showed six signal components in all patients as well as in
      the normal volunteers. During the early phase of illness, the phosphomonoester
      (PME)-phosphodiester (PDE) ratios in the patients became markedly greater than
      the ratios in the controls (P < 0.001). Within six weeks after the onset, the
      PME/PDE ratios returned to the level of controls. The time course analysis
      indicated an inverse correlation between the PME/PDE ratio and the period of time
      after onset (r = 0.738, P < 0.001). The spectral changes of human liver observed
      in acute viral hepatitis A are similar to those in the regenerating rat liver,
      indicating that 31P-NMR spectroscopy allows a noninvasive study of cell turnover
      in human liver disease associated with acute virus infection.

PMID- 8281865
TI  - Pathogenesis of varices in schistosomal portal hypertension.
AB  - Patients with schistosomiasis and portal hypertension have significantly lower
      levels of hydroxyproline in their saphenous veins and anterior rectus sheaths
      than do individuals without schistosomal hepatic fibrosis. The stomach of
      patients with schistosomal portal hypertension demonstrates an increased number
      of lymphatics by lymphangiography. The disrupted lymph node architecture in these
      patients could be partially responsible for dilation, tortuosity, and retrograde
      lymph flow in the gastric lymphatics. These histological and lymphangiographic
      findings could be attributed to the effect of venous and patients with
      decompensated schistosomal portal hypertension revealed edema of the entire
      esophageal wall with lymphatic dilation and tortuosity. Based upon these data, we
      suggest that the varices that develop in patients with schistosomal portal
      hypertension occur as a consequence of an increased portal venous pressure
      together with acquired lymphangiectasia as well as an intrinsic weakness of the
      walls of the portosystemic venous channels.

PMID- 8281866
TI  - Effect of isolated portal hypertension on Kupffer cell function.
AB  - The increased incidence of infection in cirrhotics may in part be attributable to
      dysfunction of the reticuloendothelial system (RES) in removing pathogens from
      the circulation. The portosystemic shunting (PSS) that results from portal
      hypertension in cirrhotics may compromise RES function by allowing enteric
      pathogens to be shunted away from the Kupffer cells. A well-characterized model
      of portal hypertension induced by partial portal vein ligation (PVL), in which
      there is no hepatic parenchymal cell damage, was used. Kupffer cell function is
      unaltered and the effect of PSS alone on overall RES function can be evaluated.
      In addition to the usual immunologically inert [99mTc]sulfur colloid, an actual
      pathogen was also evaluated. PVL and sham-ligated rats were given either
      [99mTc]sulfur colloid or E. coli via the ileocolic vein. The right femurs, lungs,
      livers and spleens of the animals receiving 99mTc were excised and the
      radioactivity counted. The lungs, livers, and spleens of the animals receiving E.
      coli were liquefied and the bacteria were quantified. For both groups the ratios
      of 99mTc or E. coli in the lung, spleen, and femur to liver were calculated. PVL
      rats had significantly more 99mTc in the lung, spleen, and femur than the sham
      rats. There were also significantly more E. coli in the lungs for PVL rats but no
      significant difference in the spleen counts. These results imply that even in the
      absence of Kupffer cell dysfunction, PSS alters reticuloendothelial system
      function by causing a greater distribution of pathogens to the periphery. This
      altered distribution may contribute to an increased susceptibility to infection
      in cirrhotics.

PMID- 8281867
TI  - Daytime ingestion of alcohol alters nighttime jejunal motility in man.
AB  - We studied the effects of acute ingestion of intoxicating doses of alcohol on
      jejunal motility in six male volunteers ages 24-45 who had two 24-hr ambulatory
      manometries, one week apart, that each included three standardized meals with
      either red wine (0.6 g of alcohol/kg) or dealcoholized wine. Breath alcohol was
      measured at regular intervals for 3 hr following alcohol. The results show that
      the MMC cycle was significantly (P < 0.01) shorter during the night than during
      the day in the "nonalcohol" group but not in the "alcohol" group and that the
      amplitude of contractions was higher during the night than the day in the alcohol
      group (P < 0.01). All meals interrupted the MMC and induced a fed pattern. After
      the 300-kcal liquid meal, the duration of the fed pattern was shorter (P < 0.01),
      with a lower motility index (P < 0.01) and fewer contractions (P < 0.01), than
      following the two 600-kcal meals. The number of clustered contractions occurring
      in the postprandial period was lower in the alcohol group than in the nonalcohol
      group. After the three alcohol doses, a breath alcohol peak was reached in 20-60
      min, and in all subjects, breath alcohol fell below 22 micrograms/100 ml after
      the third hour. This study showed that alcohol had only minor effects on
      postprandial contractile activity but abolished the circadian variation of the
      MMC normally seen in healthy subjects. The fact that breath alcohol was low by
      the time of onset of sleep, suggests that the effects on the MMC may be mediated
      through central rather than local mechanisms.

PMID- 8281868
TI  - Trophic effects of neurotensin in massive bowel resection in the rat.
AB  - The trophic effect of the administration of exogenous neurotensin on the
      intestinal mucosa was studied in rats following an 80% bowel resection. Villus
      length and mucosal DNA content were assessed in the jejunal and ileal mucosa of
      the remnant intestine 14 days after resection. The data obtained in an 80%
      resected control group (80% group) and an experimental group receiving an
      infusion of neurotensin (300 micrograms/kg/day) for 14 days subcutaneously (80% +
      NT group) were compared. The results indicate that the administration of
      exogenous neurotensin (80% + NT) increases villus length (jejunum: 920 +/- 77 vs
      861 +/- 25 microns and ileum length: 975 +/- 23 vs 875 +/- 99 microns) to an
      extent greater than that observed in the 80% resected group not receiving
      exogenous neurotensin. The levels of mucosal DNA per milligram of protein
      increased significantly in both groups but was paradoxically less in the 80% + NT
      group than in the 80% resection group (jejunum: 8.12 +/- 0.56 vs 10.18 +/- 0.80;
      ileum: 8.63 +/- 0.43 vs 10.05 +/- 0.46). These data suggest that the
      administration of exogenous neurotensin to the rat potentiates the growth of
      intestinal villi and accelerates the intestinal trophic response seen following
      massive bowel resection. The increase in circulating enteroglucagon levels noted
      after neurotensin administration (80% + NT: 547 +/- 48 pg/ml vs 80%: 341 +/- 41
      pg/ml) suggests that some of the trophic effects of neurotensin may be mediated,
      at least in part, by enteroglucagon. These data also suggest a potential role for
      the use of neurotensin in the initial treatment of individuals with short bowel
      syndrome.

PMID- 8281869
TI  - Plasma enteroglucagon levels in different models of intestinal resection in the
      rat.
AB  - To assess the influence of the different intestinal segments on the plasma
      enteroglucagon level, three models of intestinal resection in the rat were
      studied (jejunal, ileal, 90%). The basal values for this peptide and those
      obtained after an infusion of intraduodenal glucose were compared. The results
      obtained in basal/post-glucose infusion were: 50% proximal (jejunum): 220/728
      pg/ml; 50% distal (ileum): 10/233 pg/ml; and the middle 90%: 108/297 pg/ml. The
      glucose infusion produced a maximal response, permitting a better evaluation of
      the differences among the three resection models. The highest levels corresponded
      to the group in which the entire ileum was conserved.

PMID- 8281870
TI  - Impaired interdigestive pancreatic polypeptide release. Early hormonal disorder
      in chronic pancreatitis?
AB  - The purpose of this study was to investigate interdigestive cycling and
      postprandial release of pancreatic polypeptide (PP) in relation to exocrine
      pancreatic function in chronic pancreatitis (CP). We investigated nine patients
      with mild-moderate CP (MCP), eight patients with severe CP and steathorrea (SCP),
      and 17 healthy subjects as controls. Interdigestive antroduodenal motility was
      monitored by means of manometry. Following two consecutive motility cycles, a
      standard test meal was administered. Plasma samples were drawn for PP
      determinations every 15 min throughout the entire study, which concluded 2 hr
      after ingestion of the meal. Mean interdigestive PP plasma concentrations during
      phase III motor activity were lower in MCP (146 +/- 46 pg/ml) than in controls
      (270 +/- 42 pg/ml) and lower still in SCP (55 +/- 8 pg/ml). Accordingly, the
      percent increase in PP concentrations during phase III over those in phase I was
      progressively decreased from controls (112%) to MCP (62%) to SCP (19%). Mean
      interdigestive PP concentrations were also lower during phase I and II in SCP
      than in controls or MCP. None of the postprandial parameters for PP release was
      affected in the early stage of disease, while mean, peak, and integrated
      postprandial values were significantly lower in SCP than in controls or MCP.
      Thus, we observed a progressive diminution of both interdigestive and
      postprandial PP release with increasing severity of disease. Interdigestive
      release parameters, in particular, were tightly correlated with exocrine
      function. CP appears to alter interdigestive PP release to a greater extent than
      postprandial PP release; this effect is already apparent in early stages of the
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281871
TI  - Meal-stimulated canine jejunal ionic absorption. Influence of mucosal neural
      blockade.
AB  - The oral ingestion of a meal or the delivery of nutrients directly to the stomach
      or duodenum stimulates water and ion absorption from the proximal jejunal lumen.
      To further investigate this phenomenon, this study tested two hypotheses: (1)
      direct jejunal nutrient delivery stimulates jejunal absorption, and (2) the
      signal for jejunal absorption requires intact enteric neurotransmission and will
      therefore be altered by mucosal neural blockade with the local anesthetic
      bupivacaine. Intestinal absorption studies (N = 52) were performed on eight dogs
      with 25-cm jejunal Thiry-Vella fistulas (TVF) and feeding jejunostomies. Luminal
      perfusion with [14C]PEG was used to calculate TVF absorption of H2O, Na+, and Cl
      . Six groups were randomly studied over 4 hr. Each group incorporated a basal
      hour, a TVF or jejunostomy treatment hour, and an oral (groups 1 and 3) or a
      jejunal (groups 4 and 6) meal stimulus. The oral and jejunal meals were
      isocaloric and of identical composition. Groups 1-3 had saline (as a control) or
      0.75% bupivacaine applied to the lumen of the TVF. Groups 5 and 6 had 0.75%
      bupivacaine application to the feeding jejunostomy. Both the oral and the jejunal
      meal stimuli resulted in a significant proabsorptive response in the TVF. TVF
      bupivacaine reduced basal absorption but did not diminish the meal-induced
      proabsorptive response. Treatment of the jejunostomy with bupivacaine caused no
      change in basal or postmeal absorption in the TVF.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8281872
TI  - Expression of HLA-DR antigens on colonic epithelium around lymph follicles. An
      anomalous expression in Crohn's disease.
AB  - The relationship between the lymph follicle and expression of HLA-DR antigens on
      the colonic epithelium was investigated. Colonic specimens containing lymph
      follicles were examined immunohistochemically for HLA-DR expression. Thirty-six
      biopsy specimens (29 from macroscopically uninvolved areas and seven from
      aphthoid lesions) were obtained from 10 patients with Crohn's disease, and
      another 43 specimens were obtained from 33 patients with various intestinal
      diseases (non-Crohn's disease). HLA-DR antigens were expressed on the epithelium
      around the lymph follicle in both groups. However, the rate of expression (31/36)
      in Crohn's disease was significantly higher than that (5/43) in non-Crohn's
      diseases (P < 0.001). In addition, the extent and intensity of expression were
      broader and stronger in Crohn's disease than in non-Crohn's disease. This study
      is the first demonstration of anomalous HLA-DR expression on the epithelium
      around the lymph follicle in Crohn's disease.

PMID- 8281873
TI  - Different response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis
      according to severity of disease.
AB  - To evaluate the effect of ursodeoxycholic acid (UDCA) treatment according to the
      severity of primary biliary cirrhosis, a long-term prospective open trial in 54
      consecutive PBC patients, 19 with histological stage I-II, 24 stage III, and 11
      stage IV was carried out. UDCA was administered at a dosage of 250 mg twice a
      day. Clinical and biochemical assessment (AST, ALT, alkaline phosphatase, GGT,
      bilirubin) were done initially and every six months. Serum hyaluronate (HY) and
      type III procollagen amino propeptide (PIIIP) were also evaluated, as they are
      considered markers of fibrosis and prognosis. All patients were followed-up for
      at least two years (24-36 months); results were analyzed at 24 months after
      treatment. The composite pruritus score failed to show significant changes during
      UDCA treatment, while intensity score demonstrated a significant reduction from
      the 6th month. Patients with histological stage I-II disease had a significant
      decrease of liver enzymes (AST, ALT, alkaline phosphatase, GGT) after six months
      and maintained the levels up to 24 months. The patients with histological stage
      III disease showed a significant decrease of AST, ALT, alkaline phosphatase (but
      not GGT) up to month 18; subsequently AST and ALT serum levels increased,
      reaching values comparable to baseline by 24 months. In patients with
      histological stage IV disease no significant change in liver enzymes was observed
      during the follow-up. HY and PIIIP serum levels failed to show significant
      changes during UDCA treatment in the three groups of patients.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8281874
TI  - Effects of ranitidine 150 mg four times a day on 24-hour intragastric acidity and
      24-hour plasma gastrin concentration.
AB  - Twenty-four-hour integrated intragastric acidity and 24-hr integrated plasma
      gastrin concentration was measured twice in 23 healthy male volunteers on the
      seventh day of oral dosing with placebo or ranitidine 150 mg four times a day.
      The study was a randomized, double-blind, placebo-controlled, two-way crossover
      investigation. The mean integrated 24-hr intragastric acidity during dosing with
      ranitidine 150 mg four times a day decreased to 32% of the placebo value (placebo
      825 mmol/hr/liter; ranitidine 265 mmol/hr/liter). The mean integrated 24-hr
      plasma gastrin concentration during dosing with ranitidine 150 mg four times a
      day was 904 pmol/hr/liter compared with placebo (410 pmol/hr/liter)--an increase
      of 122%. The median number of hours of pH > 3 during dosing with placebo and with
      ranitidine 150 mg four times a day were 5 and 11 hr, respectively. Ranitidine 150
      mg four times a day caused a significant decrease of mean integrated intragastric
      acidity for each meal-related interval and also during the night.

PMID- 8281875
TI  - Omeprazole ameliorates aspirin-induced gastroduodenal injury.
AB  - Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) damage the
      gastroduodenal epithelium by two mechanisms: direct toxic effects and effects
      related to the depletion of endogenous prostaglandins. The prostaglandin-depleted
      mucosa has increased susceptibility to luminal aggressive factors, yet the role
      of acid in the pathogenesis of the NSAID ulcer is controversial. In humans,
      standard doses of H2-receptor antagonists prevent only duodenal injury and
      provide no protection for the gastric mucosa. It is not known whether more potent
      suppression of acid can prevent NSAID damage. Twenty healthy volunteers were
      randomized to a double-blind, placebo-controlled, crossover study to determine if
      omeprazole, 40 mg/day prevents gastroduodenal injury due to two weeks of aspirin
      administration (650 mg four times a day). The severity of mucosal injury was
      quantitated by endoscopy and stratified by a scale from 0 (normal) to 4 (ulcer).
      Fourteen of the 20 subjects had less gastric injury during cotherapy with
      omeprazole. All six with no difference received aspirin plus omeprazole in the
      first treatment period. Omeprazole significantly decreased aspirin-induced
      gastric mucosal injury (P < 0.001, Wilcoxon signed-rank test). Omeprazole
      protected 85% of subjects from extensive gastric erosions (often associated with
      evidence of intraluminal bleeding) or ulceration, whereas 70% of the subjects
      developed aspirin-induced grades 3 and 4 gastric injury on placebo (P < 0.01 by
      chi 2). No subject taking omeprazole developed duodenal injury of any grade,
      while 50% taking placebo developed erosions and 15% had ulcer (P < 0.001).
      Medication side effects were mild in the majority of subjects.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8281876
TI  - Lung transplantation.
AB  - Solid-organ transplantation has flourished during the last decade, with
      transplantation of heart and lungs becoming available to patients with end-stage
      cardiac or pulmonary diseases. The first lung transplant was performed in 1963 on
      a 58-year-old man with bronchogenic carcinoma. He survived for 18 days. During
      the next two decades, approximately 40 lung transplant procedures were attempted
      without success. These early attempts at lung transplantation were unsuccessful
      because of the development of lung rejection, anastomotic complications, or
      infection in the transplant recipients. In the early 1980s, human heart-lung
      transplantation was successfully performed for the treatment of pulmonary
      vascular disease. After this procedure, single-lung transplantation for the
      treatment of end-stage interstitial lung disease and obstructive lung disease was
      developed. More recently, the technique of double-lung transplantation has come
      into existence. This article reviews various aspects of lung transplantation,
      including immunosuppression, lung graft preservation, the various surgical
      techniques and types of lung transplant procedures available, recipient and donor
      selection criteria, and postoperative care of the transplant recipient. In
      addition, infectious and noninfectious complications seen in this particular
      patient population, including acute and chronic rejection, will be discussed.

PMID- 8281877
TI  - [Unusual course of candidiasis of the central nervous system].
AB  - Six months after an attack of pyelonephritis, adnexitis and candida colpitis an
      18-year-old girl developed some clouding of consciousness. On neurological
      examination she showed organic behavioural changes, discrete anisocoria and
      possible meningism. Computed tomography revealed hydrocephalus and signs of
      increased cerebrospinal fluid (CSF) pressure. CSF contained 2336/3 cells, while
      total protein was raised to 7.0 g/l and lactate concentration to 6.85 mmol/l.
      Glucose concentration in CSF was 51 mg/dl and 75 mg/dl in serum. As tuberculous
      meningitis was suspected, treatment was started with four tuberculostatic drugs,
      but there was no improvement. Five weeks later microscopic CSF examination showed
      fungal spores and nonbranching hyphae. The maximal candida haemagglutination
      titre in CSF was 1:2048. CSF culture grew Candida albicans. The further course
      was complicated by side effects to the antimycotic drugs (amphotericin B between
      4.5 and 45 mg daily; flucytosine 1.7 g four times daily) and recurrent
      obstruction in the ventricular system requiring repeated neurosurgical
      interventions. However, full cure was achieved after seven months' hospital
      treatment.

PMID- 8281878
TI  - [Transfusion associated acute pulmonary insufficiency. Diagnostic confirmation by
      the demonstration of granulocytic antibodies].
AB  - In two patients, a 50-year-old woman (case 1) and a 2-year-old girl (case 2)
      acute shortness of breath requiring artificial ventilation developed 3-5 hours
      after infusion of two erythrocyte concentrates in case 1 and unfiltered platelet
      enriched plasma (20 ml/kg) in case 2. The chest radiograph showed diffuse
      infiltrations in the lungs of both patients. After administration of
      catecholamines and respirator therapy, extubation was possible in the first
      patient after two days, in the second after five days. In neither case had there
      been any evidence of hypervolaemia, heart failure or infection to explain the
      lung findings. However, the serum of case 1 and the serum of the platelet donor
      had antibodies against granulocytes. The granulocyte-compatibility test (between
      patient serum and donor granulocytes) was positive. This confirmed the clinical
      suspicion of transfusion-related acute lung injury (TRALI). However,
      demonstration of antibodies was not only important for the diagnosis, but made it
      possible to recognize a blood donor whose serum contained antibodies against
      granulocytes which can provoke TRALI.

PMID- 8281879
TI  - [Diagnosis of familial adenomatosis polyposis].

PMID- 8281880
TI  - [Transjugular intrahepatic portosystemic stent-shunt. A new method for the
      treatment of portal hypertonia].

PMID- 8281881
TI  - [Is there a cutaneous microangiopathy in diabetes mellitus?].

PMID- 8281882
TI  - [Endobrachyesophagus].

PMID- 8281883
TI  - [Cardiopulmonary resuscitation in adults].

PMID- 8281884
TI  - [Staging laparoscopy in Hodgkin's disease].

PMID- 8281885
TI  - [Therapy of testicular teratoma in specialist centers].

PMID- 8281886
TI  - [Low-fat diet and physical training in coronary heart disease. Long-term results
      of secondary prevention].
AB  - The long-term effect of a low-fat diet and physical training was investigated in
      36 men (mean age 51 +/- 6 years) with coronary heart disease (one-vessel disease,
      n = 11; two vessel-disease: n = 18; three-vessel disease: n = 7). 18 patients
      (interventionist, group 1) undertook physical training within a coronary sport
      group (1 h twice weekly) and daily bicycle ergometry (30 min). They were held to
      a low-fat diet. In the remaining 18 patients (control, group 2), physical
      training and low-fat diet depended on own initiative after receiving advice. Over
      an observation period of 6 years total cholesterol concentration in the 17
      patients of group 1 decreased significantly (243 +/- 33 vs. 219 +/- 28 mg/dl; P <
      0.02). Physical performance in 12 patients (group 1) increased from 169 +/- 40 to
      202 +/- 42 W in (P < 0.01). In contrast, total cholesterol increased slightly in
      group 2 (n = 16) from 245 +/- 31 at the beginning to 247 +/- 39 mg/dl (no
      significant change) at the end of the 6 years. Physical performance (n = 12)
      decreased slightly from 165 +/- 45 to 146 +/- 52 W (not significant). The
      difference between the two groups was significant after 6 years (P < 0.02 and P <
      0.007, respectively). There seemed to be a tendency for progression of the
      coronary heart disease to be slower in the interventionist than the control
      group.

PMID- 8281887
TI  - Culture medium composition affects the relative toxicities of chlorobenzenes in
      rat liver slices and the isolated perfused liver.
AB  - The effects of different media composition on the hepatotoxicity produced by
      monochlorobenzene (MCB), 1,2-dichlorobenzene (1,2-DCB), 1,3-dichlorobenzene (1,3
      DCB) and 1,4-dichlorobenzene (1,4-DCB) were examined in two different in vitro
      systems. The toxicity of these chlorobenzenes was investigated in the perfused
      rat liver and liver slices using Krebs-Henseleit buffer. Significant differences
      between the chlorobenzenes were apparent in the perfused liver but not in the
      tissue slices. However, a dose and time related response of rat liver slices to
      the chlorobenzenes was observed. Partial amelioration of the chlorobenzene
      toxicity was observed when the Krebs-Henseleit buffer was supplemented with
      vitamins, amino acids, and/or bovine serum albumin. 1,2-DCB and 1,3-DCB toxicity
      was affected by amino acids and vitamins. The toxicity produced by 1,4-DCB was
      suppressed by amino acids, vitamins and 1% BSA. MCB hepatoxicity could only be
      suppressed by 1% BSA. This data suggests that tissue culture media composition
      plays a major role in the hepatotoxicity of the chlorobenzenes.

PMID- 8281888
TI  - Subchronic toxicity study of 1,3-dichloropropanone in Sprague-Dawley rats.
AB  - 1,3-Dichloropropanone (1,3-DCP) has been identified as a by-product of the
      chlorination of water and thus a potential contaminant in drinking water. Since
      little was known of its oral toxicity, subchronic exposure studies were conducted
      with male and female Sprague-Dawley rats exposed to 1,3-DCP in drinking water at
      0, 5, 65, or 125 ppm for 90 days. Evaluations included mortality, clinical signs,
      body weight, food consumption, hematology, clinical chemistry, organ weights,
      gross pathology, and histopathology. No significant organ toxicity was detected
      although an aversion to drinking 1,3-DCP treated water was observed at 65 and 125
      ppm. The only consistent change was a decrease in BUN at 125 ppm in both sexes.
      Based on a decrease in BUN levels and decreased water consumption, 5 ppm (0.5
      mg/kg/day) was considered the NOAEL.

PMID- 8281889
TI  - Ten and ninety-day toxicity studies of 2,4-dimethylphenol in Sprague-Dawley rats.
AB  - Male and female Sprague-Dawley rats received 2,4-dimethylphenol daily by gavage
      for 10 or 90 consecutive days. The 10-day acute study doses were 0, 60, 120, 600
      and 1200 mg/kg; the 90-day subchronic study doses were 0, 60, 180 and 540 mg/kg.
      Corn oil was used as the vehicle. In the 10-day study, all the high dose animals
      died. At 600 mg/kg there was a significant increase in relative liver weight in
      females and several significant alterations in hematologic and clinical chemistry
      values in both sexes. Histopathological examination revealed changes associated
      with the forestomach in all dose groups. The 90-day study had numerous compound
      related deaths at the 540 mg/kg level. In addition, the final body weight in high
      dose males and females was significantly less while absolute lung weights and
      relative liver weights in females, and relative brain, kidney and testes weights
      in males were also altered. Significant clinical chemistry findings in high dose
      animals (540 mg/kg) included reduced creatinine and increased cholesterol in both
      sexes, with increased triglycerides and decreased AST in males only.
      Histopathologic evaluation revealed hyperkeratosis and epithelial hyperplasia of
      the forestomach in males and females in the middle and high-dose groups.

PMID- 8281890
TI  - Teratogenic evaluation of p-tert-butylphenol formaldehyde resin (novolak type) in
      rats following oral exposure.
AB  - The teratogenicity of p-tert-butylphenol formaldehyde resin, novolak type, (PTBP
      FR) was examined in Wistar rats. Pregnant rats were fed diets containing 0, 2.5,
      5 or 10% of PTBP-FR ad libitum from day 6 to day 15 of pregnancy. Maternal
      toxicity, as evidenced by a decreased maternal body weight gain and food
      consumption, was observed in the 5 and 10% dose groups. However, treatment
      related clinical signs were not observed. No significant reductions in the fetal
      body or placental weights were observed in any dose group. There were no
      significant differences in the number of live fetuses, intrauterine deaths (dead
      fetuses and resorptions), or fetal sex ratios found between the PTBP-FR-treated
      and control groups. Although external and internal malformations including short
      tail, dilatation of the cerebral ventricle and the renal pelvis and dextrocardia,
      and some skeletal variations were observed in fetuses at some groups treated with
      PTBP-FR, the incidences of these morphological alterations were not statistically
      different from controls. In conclusion, PTBP-FR administered orally to Wistar
      rats during days 6-15 of gestation produced no related signs of developmental
      toxicity.

PMID- 8281891
TI  - Effects of vitamin K1 and menadione on ethanol metabolism and toxicity.
AB  - The effect of administration of two exogenous quinones on in vivo ethanol
      metabolism and ethanol-induced toxicity has been investigated. Menadione (vitamin
      K3; 50 mg/kg) or vitamin K1 (250 mg/kg) were given subcutaneously (sc) to male
      Sprague Dawley rats 1 hour before oral administration of ethanol (4 gm/kg).
      Menadione, a good quinone reductase substrate, increased the elimination rate of
      orally administered ethanol thereby decreasing its bioavailability (as measured
      by the area under the curve (AUC) relating blood level to time) and its induced
      hepatic triglyceride accumulation. On the other hand, closely related structural
      analog, vitamin K1, which was proven to be a poor substrate for quinone
      reductase, failed to show any significant effect. Thus, these results suggest
      that quinone reductase appear to play a role in in vivo ethanol metabolism and
      toxicity.

PMID- 8281892
TI  - Selenium altered regulation of heme biosynthesis in chick embryos.
AB  - A few selected indices of heme biosynthesis have been studied in liver and blood
      from chick embryos receiving different concentrations of selenium of
      toxicological significance 12.5, 25 and 37.5 mumoles/Kg egg.Wt.). The first rate
      limiting enzyme Aminolevulinic acid synthetase activity was enhanced by selenium
      treatment under both IN VIVO and IN VITRO conditions, while hepatic ALA
      dehydratase activity was unaltered. Hepatic and blood free sulfhydryl (-SH) group
      contents were significantly decreased by selenium. In accordance with these
      results, blood aminolevulinic acid dehydratase (ALA dehydratase) and hepatic
      ferrochelatase, both the sulfhydryl group requiring enzymes, were significantly
      inhibited. Further, hepatic ALA, total blood porphyrin levels were enhanced and
      hepatic heme levels were depleted by selenium exposure. These results suggest
      selenium as a novel regulator of heme biosynthesis by altering the activities of
      sulfhydryl group requiring enzymes of chick embryos.

PMID- 8281893
TI  - [Stress. Neuroendocrine aspects].
AB  - All kind of stress produce an endocrine response. These hormonal responses can
      serve as stress indicators. The main peripheral endocrine responses to stress are
      the activation of adrenal corticoids, the stimulation of Growth Hormone (GH) and
      prolactin secretion, and the inhibition of insulin and gonadal secretion. Except
      for the inhibition of insulin release, all these hormonal variations depend on
      the adenohypophysis activity: stimulation of Adrenocorticotrophin hormone (ACTH),
      GH and prolactin, and inhibition of gonadotrophins (LH-FSH) secretions. Several
      lines of evidence demonstrate that specific hypothalamic Neuro-hormones stimulate
      or inhibit the hypophysial activity in response to stress. However, due to
      methodological difficulties, only measurements of peripheral hormones can be used
      as stress indicators.

PMID- 8281894
TI  - [Stress and panic. Immunologic aspects].
AB  - Stress induces an imbalance of neuroimmunomodulation, a phenomenon involving the
      immune, central nervous and endocrine systems. Receptors to substances involved
      in stress reactions and anxiety, like adrenaline, acetylcholine, histamine,
      endomorphines, ACTH and several neuropeptides, are present on lymphocytes and
      lymphocytes can secrete various hormones and neuropeptides. Peripheral and
      central, cortical and subcortical nervous structures influence immune response.
      Steroids play a dose dependent inhibitory role perhaps via GIF (Glucocorticoid
      Increasing Factor) and cytokines (IL 1). In rats, stress induces an increase of
      corticosterone levels and a lymphopenia depending on the presence of adrenals and
      pituitary, whereas functional responses to mitogens appear decreased in animals
      even after surgical removal of adrenals and/or pituitary. Immune response vary
      according to the degree of control over stressors, to the type of stressor and
      the animal species. Chronic or repeated stress tends to stimulate immune
      reaction, contrary to acute stress. In man grief reactions, terminal illness of a
      spouse, divorce, examinations, caregiving to Alzheimer patients have been used as
      models of stress, with immune consequences. Pathological anxiety has been less
      studied, with only few anomalies reported in DSM III-R panic disorder. The immune
      system participation in the adaptive response to stress is reviewed.

PMID- 8281895
TI  - [Stress and panic. Psychoanalytic aspects].
AB  - In 1956, Selye described the reactions of the human body when confronted to an
      aggression. The psychoanalytic point of view was much anterior to Selye's
      researches and works, provided a wider perspective for a better understanding of
      the different ways a patient would react when facing a "stressing event". Freud
      brought out the concept of the "psychic trauma" whose origin might be due to a
      precocious process of sexual seduction. It was also noted that its source could
      be found in the fantasmatic activity of the patient. Other signs of the psychic
      trauma have been observed as the effect of an absence or of a lack of excitement.
      Finally, in some circumstances, the psychical trauma may contribute to build a
      positive structure for the "EGO" because of the changes it implies and allows.

PMID- 8281896
TI  - [Stress and the digestive system].
AB  - Functional disorders mainly occur in young, anxious hyperactive, sometimes
      obsessional patients and involve all parts of digestive tract: feeling of
      obstruction the upper oesophagus or dysphagia; aerophagia related to a slow
      gastric emptying or gastric fullness relieved by eructation; biliary vomiting and
      pain in right abdominal upper quadrant which might correspond to a form of
      migraine without headache; irritable bowel, characterized by abdominal discomfort
      and constipation. Obviously, the diagnosis of functional disorders required
      elimination of an organic disease by appropriate endoscopic investigations.
      Psychosomatic disorders mainly comprise gastroduodenal ulcers and inflammatory
      bowel diseases. Although psychologic profiles have been associated with gastro
      duodenal ulcer, these are not necessary for the development of the disease. The
      role of emotional factors has decreased since very efficient anti-secretory drugs
      are available. Inflammatory bowel diseases, in particular ulcerative colitis is
      frequently associated to behaviour disorders. The patient is usually a young
      woman brought up by an overprotective family. It is generally recognized that
      attacks of ulcerative colitis may be triggered by emotional factors. Thus, Stress
      may interact with digestive tract. In some cases, as in patients with irritable
      bowel or distal ulcerative colitis, psychotherapy such as Schultz's Autogenous
      Training, improves the patient's condition.

PMID- 8281897
TI  - [Stress and the cardiovascular system].
AB  - A variety of evidence shows that stress contributes to a more or less sustained
      elevation of blood pressure, as well as to the triggering and aggravation of
      cardiovascular pathology, especially coronary heart disease. Experimentally
      induced changes, that may be pathogenic due to their duration or repetition, can
      be produced in hemodynamics, lipid metabolism, or hemostasis. High blood
      pressure, vascular heredity, but also a trend to inhibition of action, seem to be
      responsible for hyperreactivity to stress. Hypertensives are particularly
      reactive to active stresses related to controlable situations, experienced as
      challenges. Several prospective studies in healthy subjects have confirmed the
      increased risk for coronary heart disease of certain psychological
      characteristics: the most known of them is Rosenman's and Friedman's type A
      behavior (hyperactivity, speed and impatience, hard driving, job involvement). It
      is known that individuals presenting such characteristics exhibit increased
      neuroendocrine responses to all types of stress. Pattern A predicts the incidence
      of myocardial infarction, independently of other coronary risk factors, such as
      hypertension, hypercholesterolemia, or smoking habits. It as been proved that
      type A individuals deal on average with more stressing conditions than type B
      individuals and that they set higher goals than general population. On a
      cognitive level, they tend to have an internal "locus of control" (they are
      inclined to attribute their personal successes or failures to their own
      responsibility). Nevertheless, the most reactive to stress among type A
      individuals are those whose locus of control is external. The predictive validity
      of pattern A in coronary mortality is more debated.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8281898
TI  - [Stress and depression].
AB  - Stress largely influences our depression models. Animal models of depression and
      for the detection of antidepressants, and severity of psychosocial stressors
      scale have emphasized the role of stress in depression. Life events, who are
      understood as social stressors, may be recent prior to onset (6-12 months) of
      depression (provoking agents) or remote e.g. loss of parent in childhood
      (predisposing factors). Many results from studies must be interpreted cautiously
      because of retrospective designs and other methodological limitations. Among
      predisposing factors, loss due to separation may have a greater influence than
      loss due to death of a first-degree relative. Neurotic depressives sometimes have
      more provoking life events than endogenous depressive subjects but there is no
      difference in the augmentation of these life events prior to the onset of
      depression. Concerning the relapses and the recurrences, Kraepelin noted that the
      onset of new episodes seemed to become more autonomous. Several data do not
      confirm this classic position. What influence has the maintenance treatment on
      the stress reaction? Several psychosocial models of depression have taken into
      account the interactions of stress, life events and depression. In Harris and
      Brown's and Seligman's models, particular attention has been given to the notion
      of vulnerability in relation to the aetiology of depression. The view that
      neither vulnerability nor provoking agents by themselves explain the disorder
      gives rise to an alternative representation (Dohrenwend). Coping is of great
      interest to epidemiologists and geneticists in the problems of mental
      illness.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281899
TI  - [Psychosocial stress factors and suicidal acts].
AB  - Suicidal behaviour is actually understood as being multidetermined and the result
      of an interaction between state and trait related effects. Several types of risk
      factors have been extensively studied: psychiatric and personality disorders,
      genetic variables, biological factors and psychosocial stressors, the latter
      being the purpose of this review. Social and familial factors, negative life
      events and medical illness may interact with the factors mentioned above in three
      main ways to produce suicidal acts: as predisposing factors increasing
      vulnerability, as precipitating or as contributing factors. A summary of social
      and clinical studies will be presented and implications for medical care and
      prevention will be discussed.

PMID- 8281900
TI  - [Stress, anxiety, panic. Panic attack and panic disorder. A new psychiatric
      concept].
AB  - Pathological anxiety--painful and incapacitating--can be defined as perception of
      stress with cognitive distortion. The traditional unitary model of anxiety
      neurosis is replaced by the american model (DSM III) with "panic disorder" and
      "panic attacks" representing the cornerstone of the new construct, based on the
      evidence (by Donald Klein) of the efficacy of so-called antidepressant drugs.
      Behavioral and cognitive treatments are useful, mainly in anxiety with
      agoraphobia. "General anxiety disorder" is now considered as a "residual
      category". Clinical aspects, differential diagnosis, circumstances of onset,
      pharmacological induction of panic attacks (specially by lactate and caffeine),
      and treatments, are reviewed.

PMID- 8281901
TI  - [Behavioral and cognitive strategies in stress management].
AB  - Stress is a specific response of the individual to all nonspecific demands.
      However, this process of adaptation is very complex and varies considerably from
      person to person. The stress response or "stress reactivity" is triggered by
      various stressors, ranging from live events to daily hassles and including
      chronic stressors. These stressors need to be identified. The stress response is
      not univocal: it has physiological, cognitive and behavioral components. Most of
      the time, physiological, cognitive and behavioral responses are maladaptive and
      harmful for the individual. Stress management is directed at teaching individuals
      specific skills to modify parts of these responses in order to reduce stress.
      Relaxation therapies are the cornerstone of any stress management program. They
      mostly include autogenic training and progressive relaxation training, sometimes
      biofeedback. The relaxation response is a learned response. There are a variety
      of different methods of inducing this response. They share the common goal of
      countering the physiological aspects of the stress reaction. All the relaxation
      techniques involve long and exacting training. But proper training leads to a
      gradual reduction in time and effort required to relax. When properly pursued,
      these techniques produce a state of relaxation quickly and on demand. Cognitive
      approaches to stress management derive from the constatation that the
      individual's interpretation of events or situations which have been labeled
      stressful, the individual's anticipation of the consequences of the stressor and
      the individual's view of his or her ability to cope with the stressor or the
      stress reaction are fundamental in the stress process. There are a variety of
      cognitive theories and techniques, ranging from Beck's cognitive therapy to
      Ellis' Rational-Emotive Therapy. Initial phases of these therapies are directed
      at teaching the individual to recognize, record, analyse and modify maladaptive
      cognitions. The second phase is usually devoted to identifying and modifying the
      dysfunctional attitudes which give rise to the stressful cognitions. The basic
      behavioral stress response falls in line with the expectations of the fight or
      flight response, and a stressed individual will typically display a pattern of
      either aggressive or avoidance behavior (as shown in the "Type A Behavioral
      Pattern"). The relation between stress and behavior is bidirectional: some
      behaviors occur in response to stress, whereas others produce stress. Assertive
      training is often a component of stress management programs as it is accepted
      that behaving in an assertive manner (i.e. a non passive and non aggressive
      manner) results in an increased feeling of well-being.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8281902
TI  - [Drugs for stress].
AB  - Speaking of "drugs of stress" is difficult because stress is not a so precise
      concept. Moreover, the target is not simply the correction of physiological
      responses to a stimulus, but is the treatment of pathologies which are directly
      related with stress: post-traumatic stress disorders (PTSD) and performance
      anxiety. Drug treatment of PTSD is not well codified, even if phenelzine and
      amitriptyline are, at least relatively, effective medicines. Beta-blockers remain
      today the main drugs for performance anxiety. Studies about the utility of
      carbamazepine and clonidine in these disorders are few. Experimental works upon
      the action of tianeptine on hippocampus cells lead to interesting results. The
      place of benzodiazepines and neuroleptics is still controversial.

PMID- 8281903
TI  - [Introduction to chronic depression and resistant depression].
AB  - Chronic depression actually covers several different nosographic entities. Among
      the predictive factors for chronicity, personality disorders raise the complex
      issue of the relationship between traits and depression. Some approaches favour
      the concept of premorbid personality, others in contrast insist more on
      personality disorders which complicate a depressive episode. In order to account
      for both stress factors and biological factors in the progression of depression
      towards chronicity, Post suggested in 1992 a bold integrative pattern. In this
      pattern, the premorbid period would be marked by secondary sensitization to
      repeated stress factors. These factors would cause not only short-term but also
      longer-term fragility by modifying the transcription of protein encoding, in
      particular for the C-fos oncogene. This would cause peptide alterations which
      originate a vulnerability to mood disorders. With time, an accumulation mechanism
      and a kindling phenomenon would cause the initial depressive episode to develop,
      and that in turn would constitute a new vulnerability factor for the new
      spontaneous occurrence of further depressive episodes. This model has the merit
      to underline the importance of early and durable treatment. It also suggests a
      promising approach for the future.

PMID- 8281904
TI  - [Dysthymic disorder and its treatment].
AB  - Dysthymia is a new nosographic category in the latest American and international
      classification of mental disorders. Dysthymics were previously considered either
      as "neurotic depressive characters" or "characterologic depressives." Today it
      has been demonstrated that the personality and affective traits of these patients
      are in fact simply different expressions of a constitutive predisposition to
      clinical depression. Some studies have shown biological and neurophysiological
      relationships between dysthymia and major mood disorders. We therefore submit
      that dysthymia constitutes a subaffective expression of the major depression
      phenotype. Other studies have demonstrated the short-term efficacy (6 weeks to 3
      months) of antidepressants in this disorder. In this article, we present a
      prospective 2-years study comparing the efficacy of fluoxetine with tricyclic
      antidepressants. The results show not only the efficacy of fluoxetine in
      dysthymia, but especially, if we consider the degree of social adaptation, a much
      better response qualitatively. These patients, who were previously sentenced to a
      life of suffering, may now benefit from new mood-regulating agents. The benefit
      afforded by drug treatment must be supported by various supportive
      psychotherapies, which are also discussed.

PMID- 8281905
TI  - [Chronic depression and its treatment].
AB  - Can depression still be defined today as a transient abnormal state which is
      reversible with treatment? Chronic depression affects about one out of five
      depressed subjects. The progression to chronicity has a multifactorial
      determinism; it includes sociodemographic, medical and psychopathological
      parameters. These depressions are sometimes difficult to diagnose, all the more
      as there are no definitely established nosographic criteria. One usually
      considered is the persistence over more than two years of depressive symptoms
      and/or of socioprofessional dysfunctions. First-line treatment is based on
      uninterrupted prescription of a well-tolerated antidepressant for over two years,
      with dosage maintained at the acute phase level. In the event of a failure, there
      is as yet no well-defined alternative therapy. Because of their socioprofessional
      repercussions, chronic depressions may become a significant public health issue.
      They need imperiously that prospective long-term evaluation studies be
      implemented.

PMID- 8281906
TI  - [Contributions of pharmacology in the treatment of resistance to antidepressive
      agents].
AB  - Pharmacology can contribute in four ways to our understanding and to the
      management of resistant depression: 1) Dosage: some antidepressants have an
      inverted-U dose-response curve, i.e. the response disappears when dosage is
      increased. In man, dose-response relationships are not well established because
      the curves are obtained with groups of patients and they reflect an overall mean
      rather than the reality of each individual patient. 2) Secondary regulatory
      adaptive mechanism such as: down regulation of beta, 5-HT2, alpha-2 receptors-
      increased reactivity of 5-HT1A, alpha-1 and dopaminergic systems. Defective
      development of these mechanisms is thought to originate resistance in certain
      cases, which could therefore be corrected more or less specifically by adding
      thyroid hormone, lithium, an alpha-2 agonist or even by switching to a 5-HT1A
      agonist or a dopaminergic drug. 3) Biological resistance factors: it has been
      shown in the rat that hypothyroidism, diabetes, weight loss cause a decrease in
      beta-adrenergic system reactivity, and therefore a resistance to noradrenergic
      antidepressants. 4) Co-prescription: the efficacy of noradrenergic
      antidepressants is known to involve the activation of beta-adrenergic receptors.
      Animal studies have shown that the co-prescription of a beta-blocker nullifies
      this efficacy. Benzodiazepines decrease serotonergic and noradrenergic neuronal
      activity: animal studies have shown that they antagonize most antidepressants.
      What happens in depressed humans who are often co-prescribed these drugs? I would
      like to share with you a few data from experimental pharmacology which may help
      us to think differently, not when faced to a patient with resistant depression,
      but when confronted with the failure of a well conducted antidepressant
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281907
TI  - [A scale for clinical evaluation of serotonergic deficit in elderly people].
AB  - In contrast to young adults, symptoms of serotonergic deficiency are relatively
      undocumented in elderly subjects. Specific abnormalities of serotonergic
      neurotransmission are nevertheless remarkable and have clinically important
      repercussions in affect, as well as in cognition and behavior. The aim of this
      study was to develop a scale for the clinical and transnosographic quantitation
      of serotonergic deficiency in elderly persons (5-HT scale). Based on the data in
      the literature and following a preliminary study, we developed a 10-point scale.
      The analysis into primary components, among 155 subjects, showed a stable
      factorial structure and highly saturated "pure" items (62 to 90) distributed into
      4 factors: "loss of control", "anxiety-insomnia", "depression" and "disturbances
      of behavior". The factorial structure does not depend on the psychiatric
      diagnosis: the 5-HT scale is not correlated with the COVI anxiety scale, the
      Jouvent mood scale, the Widlocher slowing down scale or the Hamilton depression
      scale in the subgroup of depressed subjects. Factorial analysis on the cumulated
      items of the 5-HT and Hamilton depression scales shows dispersion of the items on
      the latter scale whereas those on the 5-HT retain a factorial distribution. These
      data seem to confirm the clinical importance of serotonin deficiency in elderly
      subjects and the pertinence of the transnosographic approach. The 5-HT scale,
      which still requires outside validation, would seem to contribute to the clinical
      evaluation of this deficiency.

PMID- 8281908
TI  - [Antidepressive agents and memory].
AB  - It is important that antidepressants, now increasingly used in ambulatory
      treatment of many patients, should not be detrimental to cognition and memory. It
      is difficult to assess these effects. One must make a distinction between the
      direct effects of antidepressants on cognition, related to their intrinsic
      properties, and indirect effects secondary to mood improvement. The tests used in
      studies essentially focus on psychomotricity and do not accurately evaluate the
      effects on cognition itself. Indeed, there are different kinds of memory which
      would require specific investigations. It has nevertheless been demonstrated that
      acute administration of sedative antidepressants with a marked anticholinergic
      component are detrimental to the memory processes. However, following prolonged
      administration, tolerance may develop within 1 to 3 weeks. Some antidepressants,
      however, especially serotonergics, do not cause any disturbances of memory. In
      depressed subjects, it seems that, overall, long-term antidepressant treatment
      improves cognitive functions. This effect is due to the combination of drug
      tolerance and of the indirect effects secondary to mood improvement. Elderly
      subjects appear to be more sensitive to the detrimental effects on memory and
      they develop drug tolerance more slowly. Lastly, two studies have reported that
      serotonin re-uptake inhibitors might have beneficial effects on memory disorders
      secondary to acute or chronic alcohol abuse.

PMID- 8281909
TI  - [Obsessive compulsive disorders].
AB  - Obsessive compulsive disorders (OCD) are a nosographic entity. Their biological
      rating in serotonergic pathways and the efficacy of serotonergic antidepressants
      allows for developing a clinical and biological models of OCD. J. Guyotat, one of
      the first in 1959 to observe the favorable effects of antidepressants on OCD,
      presents their history. Epidemiological surveys conducted since 1980 have shown
      that the prevalence of OCD was underestimated until then. The prevalence is 2 to
      3% in the adult population, with more women affected. The disorder develops early
      in childhood and adolescence. Loss of time is an important criteria for OCD but,
      according to M. Bourgeois, who reviewed the symptoms precisely, this does not
      warrant identifying a separate "primary obsessive slowness" syndrome. According
      to M. Bouvard, the prognosis of the disorder, in contrast to that for rituals
      observed in children between 3 and 5 years of age, is poor, with a risk of
      chronicity and social disturbances. The prevalence of OCD in children and
      adolescents is 0.8% and remains stable. The comorbidity, in particular with tics,
      is discussed. The favorable effects of fluoxetine are reported. J.M. Chignon
      reviews the concept of comorbidity, developed in internal medicine, and explains
      that it could be rigorously applied to psychiatry only starting with the DSM III
      R. The comorbidity of OCD with other psychiatric diseases is highly variable: it
      is reviewed for personality disorders (0 to 55%), schizophrenia (4%), substance
      abuse (10%) and especially depression: one third of patients with OCD will
      develop a major depressive episode. Based on a clinical case report, M. Faruch
      leads us from symptoms to behavior therapy. The symptom must be considered for
      itself, whether it is part or not of the obsessive neurosis. It is legitimate to
      use antidepressants in combination with behavior therapy.

PMID- 8281910
TI  - High glucose causes delayed fetal lung maturation in vitro.
AB  - The diabetic pregnancy is characterized by a delay in the process of fetal lung
      maturation. To determine whether high glucose conditions per se have an adverse
      impact on fetal lung phospholipid metabolism, 20-day fetal rat lung explants were
      cultured in F-12 medium (10 mM glucose) to which glucose was added to achieve
      final concentrations of 10, 25, 50, and 100 mM. Significant dose-dependent
      decreases in the rate of incorporation of [H3]choline into PC were noted at high
      glucose concentrations: Rate of choline incorporation was decreased by 19 and 28%
      under 50 and 100 mM glucose conditions, respectively (p < .001). Similar results
      were obtained when choline incorporation into DSPC was assayed. Equiosmolar
      mannitol concentrations did not result in comparable decreases, indicating a
      specific adverse effect attributable to glucose. Total PC and DSPC contents were
      also decreased by approximately 25% under high glucose conditions (p < .001).
      Glycogen concentrations were increased two- to threefold in the explants grown
      under high glucose conditions, consistent with a less mature lung. The addition
      of 1 unit/mL of insulin to F-12 medium did not result in decreases in choline
      incorporation into PC or DSPC; the addition of this amount of insulin to medium
      containing 100 mM glucose did not result in further decreases in choline
      incorporation rate. These results indicate that high glucose alone can have an
      adverse effect on fetal lung maturation in vitro and may be involved in the
      pathogenesis of the delay in fetal lung development observed in the diabetic
      pregnancy.

PMID- 8281911
TI  - Experimental hypersensitivity pneumonitis in mice induced by Trichosporon
      cutaneum: histologic and immunologic features and effect of in vivo depletion of
      T cell subsets.
AB  - An animal model of hypersensitivity pneumonitis (HP) was developed in C57Black/6J
      mice by repeated intratracheal inoculations with particulate Trichosporon
      cutaneum, a causative agent of Japanese summer-type HP. We observed severe
      alveolitis and bronchiolitis with infiltration of lymphocytes, macrophages, and
      neutrophils in the lung lesions. Granuloma formation was occasionally seen.
      Bronchoalveolar lavage (BAL) of the experimental animals showed an increase in
      the number of lymphocytes, macrophages, neutrophils, and in the total cell yield.
      Phenotypic analysis of the BAL lymphocytes by flow cytometry revealed that 43.1
      +/- 3.1% of lymphocytes were Thy1.2+ (CD3+) cells and that the L3T4+ (CD4+) cells
      (36.3 +/- 3.5%) predominated over the Lyt2+ (CD8+) cells (18.5 +/- 1.2%). As for
      the humoral immune response, the specific IgA antibody activities in the BAL
      fluids well reflected the specific pulmonary inflammatory responses. Studies of
      lymphocyte depletion were performed by in vivo administration of anti-CD4 and
      anti-CD8 monoclonal antibodies. Depletions of CD4+ cells and of both CD4+ and
      CD8+ cells diminished the pulmonary lesions and specific IgA antibody activities
      in the BAL fluids. These results indicate that CD4+ cells may play a major role
      in the inflammatory process of this animal model.

PMID- 8281912
TI  - Human tracheobronchial deposition and effect of two cholinergic aerosols.
AB  - The effects of two methacholine aerosols with mass median diameters congruent to
      7 and 3 microns were measured in 10 healthy subjects. The concentrations of the
      two aerosols were increased until forced expiratory volume in 1 s (FEV1)
      decreased with about 20%. Pulmonary fraction (FEV1, FVC, FEV25-75%, FEF75-85%,
      R(aw), and phase III of single breath O2 test) and deposition of 3.6-microns
      radiolabeled Teflon particles were studied before and after bronchial challenge
      with the two aerosols. Output from the nebulizers and size distribution were
      measured and from these data and from data on deposition of Teflon particles from
      this and seven earlier studies the doses of the two methacholine aerosols to the
      tracheobronchial region were calculated. The changes in all pulmonary function
      parameters and deposition of 3.6-microns particles were similar for the two
      aerosols. The calculated dose for the aerosol with the large particles was 3-4
      times higher than that with the smaller particles. The results indicate greater
      effect of a certain dose to the tracheobronchial part of the lung if the mass is
      spread on many small particles than on fewer large ones.

PMID- 8281913
TI  - Most of the lipid in purulent sputum is bound to mucus glycoprotein.
AB  - Mucus glycoprotein (mucin) is the principal biochemical constituent of sputum.
      Appreciable quantities of lipid, DNA, and nonmucin proteins are also present,
      particularly in purulent sputum. Previous studies have shown that purified mucin
      from respiratory tract secretions contains non-covalently bound lipid. However,
      it is not known whether lipids in purulent sputum are associated only with mucin
      or with nonmucin proteins and DNA as well. Purulent sputum was obtained from
      cystic fibrosis patients. Tracheal aspirates were obtained from noncystic
      patients with purulent secretions due to Pseudomonas species, as well as from
      noninfected, noncystic patients who had mucoid airway secretions. The lipid
      content of unfractionated airway secretions (sputum or tracheal aspirates), gel
      filtration-purified mucin, and nonmucin components of the airway secretions was
      analyzed. The purified mucin from all three groups had a significantly higher
      content of solvent-extractable lipid as compared to unfractionated airway
      secretions. The nonmucin fractions contained only small amounts of lipid. Density
      gradient centrifugation verified that the lipid recovered in the purified mucin
      fraction was complexed with the glycoprotein. The results of this study indicate
      that most of the lipids in purulent sputum are associated with mucin.

PMID- 8281914
TI  - Role of thyroid hormone in de novo synthesis of cholinephosphotransferase in
      guinea pig lung mitochondria and microsomes.
AB  - It is known that thyroid hormone enhances the biosynthesis of phosphatidylcholine
      in the lung. The purpose of the present study was to investigate the effects of
      thyroid hormone on the activity of cholinephosphotransferase, the terminal enzyme
      in the CDP-choline pathway, in guinea pig lung mitochondria and microsomes.
      Intramuscular injection of triiodothyronine (T3, 0.25-4 mg/kg body wt) stimulated
      the activities of both mitochondrial and microsomal enzymes in a dose-dependent
      manner. However, the stimulation was much more pronounced in the microsomes than
      in the mitochondria. The stimulatory effect of T3 was blocked by the
      intraperitoneal injection of both actinomycin D and cycloheximide in the
      microsomes, whereas in the mitochondria, the hormonal effect was blocked only by
      cycloheximide. Thus, it is suggested that T3 stimulates not only the
      nucleocytoplasmic system for the de novo synthesis of the enzyme, but possibly
      also the regulation of the transport of the synthesized protein into the
      mitochondria. Furthermore, administration of T3 produced an increase in the
      uptake and incorporation of [14C]choline into phospholipids of lung slices in
      vitro. However, this effect was blocked by intraperitoneal injection of both
      actinomycin D and cycloheximide. Thus, the change in CPT activity by T3 in
      mitochondria is not reflected by enhanced incorporation of choline into
      phosphatidylcholine.

PMID- 8281915
TI  - Pulmonary vascular responsiveness in rats following neonatal exposure to high
      altitude or carbon monoxide.
AB  - Exposure of adult and neonatal rats to high altitude increases pulmonary vascular
      responsiveness during the exposure. A study was undertaken to determine if a
      short exposure of neonatal rats to either high-altitude or carbon monoxide (CO)
      hypoxia would cause persistent alterations in pulmonary vascular responsiveness
      postexposure. One-day-old male Sprague-Dawley rats were obtained as 16 litters of
      10-12 pups each. At 2 days of age, 4 litters were exposed to CO (500 ppm) for 32
      days, and 4 litters were exposed to ambient air (AIR) in Detroit (200 m). Another
      4 litters were exposed to 3500 m altitude (ALT) in a chamber for 32 days, and 3
      litters were exposed to ambient conditions in Fort Collins (CON, 1524 m). After
      the exposures, all rats were maintained at 1524 m. At 2, 40, 76, and 112 days
      postexposure, lungs were isolated and perfused with Earle's salt solution
      (+Ficoll, 4 g%). Pulmonary vascular responsiveness was assessed by dose responses
      to angiotensin II (AII, 0.025-0.40 micrograms) and acute hypoxia (3% O2 for 3
      min). AII responses were higher in ALT vs CON rats at all ages, but no
      differences were noted between CO and AIR rats. Acute hypoxic responses were
      higher in ALT versus CON rats at 2 and 40 days postexposure, but no differences
      were noted between CO and AIR rats. Baseline pulmonary vascular resistance and
      pulmonary arterial pressure (in isolated lungs) were higher in ALT rats at all
      four ages compared to the other three groups. Both the ALT and CO rats displayed
      hypertrophy of the right ventricle (RV) and the left ventricle (LV) at the
      termination of treatment and elevated hematocrit. LV hypertrophy and polycythemia
      regressed with time, but RV hypertrophy remained significant in the ALT rats
      through 112 days postexposure. The results indicate that neonatal exposure to
      ALT, but not CO, causes a persistent increase in pulmonary vascular
      responsiveness and RV hypertrophy for at least 112 days after termination of the
      exposure.

PMID- 8281916
TI  - Pichinde virus-induced respiratory failure due to obstruction of the small
      airways: structure and function.
AB  - Respiratory distress that leads to death is seen in patients with Lassa fever.
      The development of this respiratory problem was studied using a Pichinde virus
      model (10(4) plaque forming units, IP, survival time 20 +/- 1 days) in strain 13
      guinea pigs (n = 35, 229-353 g) of this lethal human contagious infectious
      disease. Extravascular lung water to bloodless dry lung weight (EVLW/BDLW) ratio
      showed a modest yet significant increase in animals 13 and 18-21 days
      postinoculation (PI). In contrast, residual lung blood and lung radioactive 125I
      labeled human serum albumin activity index were elevated only in the 18- to 21
      day group. These data are consistent with the progressive severity of
      perivascular edema, lymphocytic pneumonitis, and some alveolar protein between
      days 13 and 18-21 PI. Lymphocytic pneumonitis appeared to be distributed near
      most airways and was proportional to the degree of Pichinde virus antigen
      staining of alveolar macrophages, large mononuclear cells within the pulmonary
      vascular and extravascular spaces, and alveolar-capillary membranes. These
      findings suggest that lymphocyte recruitment to the lung reflects the Pichinde
      virus-induced cell-mediated immune response. Obstructed small bronchi with some
      lumenal cell debris and hypertrophied epithelial cells were found associated with
      the areas of marked pneumonitis. The severe hypoxemia and modest anaerobic
      metabolism in association with marked tachypnea and normocapnia are consistent
      with small airway obstruction and wasted ventilation, since no change in arterial
      blood pressure, heart rate, hematocrit, hemoglobin, or blood volume was noted.
      These data suggest that Pichinde virus-induced respiratory failure was due to
      obstruction of the small airways with wasted ventilation in association with
      lymphocytic pneumonitis.

PMID- 8281917
TI  - Electron microscopic analysis of the normal and the activated pleural macrophage.
AB  - Despite an apparent role in pleural pathophysiology, little information is known
      about pleural macrophage morphology. Intrapleural tetracycline (TCN) results in
      pleural macrophage influx and pleural fibrosis; intrapleural carrageenan (CAR)
      induces macrophage influx without ensuing fibrosis. Pleural macrophages collected
      from normal (NL) and TCN- or CAR-exposed rabbit pleural spaces were examined with
      electron microscopy. Cellular size; number of microvilli; pseudopods; coated pits
      (CP) and coated vesicles (CV); and prevalence of golgi, rough endoplasmic
      reticulum (RER), and intermediate filaments (IF) were determined. The means of
      each variable in each group were assessed by one-way analysis of variance, with
      post hoc testing performed by Scheffe F test; p < or = .05 was considered
      significant. TCN-stimulated pleural macrophages were characterized by their small
      perimeters. CAR-induced pleural macrophages were marked by their large size and
      abundant intracellular amorphous material. They had larger perimeters, areas, and
      diameters than the TCN-induced or normal macrophages and thus smaller numbers of
      CV + CP per area. The normal pleural macrophages were characterized by more IF,
      microvilli, and microvilli per perimeter than either the CAR- or TCN-induced
      pleural macrophages. No differences between groups were found in nuclear
      cytoplasmic ratios, number of pseudopods, and content of golgi or of RER. The
      results suggest that normal pleural macrophages and TCN- and CAR-induced pleural
      macrophages differ morphologically and that these morphologic differences reflect
      functional differences.

PMID- 8281918
TI  - The complex between ribonuclease T1 and 3'GMP suggests geometry of enzymic
      reaction path. An X-ray study.
AB  - The crystal structure of the complex between ribonuclease T1 and 3'GMP suggests
      that (a) a substrate GpN is bound to the active site of ribonuclease T1 in a
      conformation that actively supports the catalytic process, (b) the reaction
      occurs in an in-line process, (c) His40 N epsilon H+ activates O2'-H, (d) Glu58
      carboxylate acts as base and His92 N epsilon H+ as acid in a general acid-base
      catalysis. The crystals have the monoclinic space group P2(1), a = 4.968 nm, b =
      4.833 nm, c = 4.048 nm, beta = 90.62 degrees with two molecules in the asymmetric
      unit. The structure was determined by molecular replacement and refined to R =
      15.3% with 11,338 data > or = 1 sigma (Fo) in the resolution range 1.0-0.2 nm;
      this includes 180 water molecules and two Ca2+. The structure of ribonuclease T1
      is as previously observed. 3'GMP is bound in syn conformation; guanine is located
      in the specific recognition site, the ribose adopts C4'-exo puckering, the ribose
      phosphate is extended with torsion angle epsilon in trans. The O2'-H group is
      activated by accepting and donating hydrogen bonds from His40 N epsilon H+ and to
      Glu58 O epsilon 1; the phosphate is hydrogen bonded to Glu58 O epsilon 2H, Arg77
      N epsilon H+ and N eta 2H+, Tyr38 O eta H, His92 N eta H+. The conformation of
      ribose phosphate is such that O2' is at a distance of 0.31 nm from phosphorus,
      and opposite the P-OP3 bond which accepts a hydrogen bond from His92 N epsilon
      H+; we infer from a model building study that this bond is equivalent to the
      scissile P-O5' in a substrate GpN.

PMID- 8281919
TI  - Reverse micelles as a water-property-control system to investigate the
      hydration/activity relationship of alpha-chymotrypsin.
AB  - alpha-Chymotrypsin, solubilized in hydrated reverse micelles of sodium bis(2
      ethylhexyl)sulfosuccinate (AOT) in n-octane, was used as a model system for
      studying the involvement of different water structures (strongly bound water,
      disordered water, water clusters and bulk water) in the development of the
      catalytically active conformation of the enzyme. Results presented in this study
      indicate a characteristic dependence of the stability/activity profile on the
      water content of the reverse-micellar system for values of wo of approximately 5
      (wo is defined as [H2O]/[AOT]). The results are consistent with heat-capacity
      measurements for proteins. At very low wo values, the conformation of alpha
      chymotrypsin changes to a very rigid structure in comparison to the structure
      observed in water. This is demonstrated by the overall center of gravity of the
      tryptophan fluorescence spectrum of the enzyme at wo = 0.65, which is blue
      shifted in comparison to the spectrum in bulk water indicating that the enzyme is
      in an apolar environment. In the absence of a hydration shell, the protein is to
      a great extent frozen and inactive. A small increase in the level of enzyme
      hydration (up to wo = 2.3) causes an increase in the amount of strongly bound
      water associated with the enzyme and the enzyme displays a high catalytic
      activity. Upon further addition of water, a new unstable water structure with
      unfavourable enthalpy is developed and the enzyme activity declines, reaching a
      minimum at wo = 5.1. A new increase of water content within a relatively small
      range, wo = 5-8, causes a dramatic increase in enzymic activity, reminiscent of a
      cooperative hydration dependence. In the range wo = 10-29, the effect of
      hydration on the activity is complete which shows that the enzyme activity
      depends on the amount of water in contact with the enzyme and not on the total
      amount of bulk water in the system. The experimental results on enzyme incubation
      at different wo values followed by dilution to constant high wo, are indicative
      of inactive conformational substates of alpha-chymotrypsin. It is demonstrated
      that highly active enzyme conformations at very low, wo values occur via an
      induced fit mechanism of substrate binding.

PMID- 8281920
TI  - A specific interaction between NADPH-cytochrome reductase and phosphatidylserine
      and phosphatidylinositol.
AB  - In the present study the interaction of NADPH-cytochrome reductase with
      phospholipids was investigated using 31P-NMR, thin-layer chromatography combined
      with chemical analysis, fluorescence spectroscopy and kinetic studies with
      purified rat liver cytochrome P450 IIB1. 31P-NMR analysis demonstrates that the
      composition of the phospholipids that remain associated to NADPH-cytochrome
      reductase upon its purification is significantly different from the phospholipid
      composition of the microsomal membrane. Thin-layer chromatography followed by
      chemical analysis of the phospholipid composition demonstrates that the isolated
      NADPH-cytochrome reductase was enriched in L-alpha-1,2-diacyl-sn-glycero-3
      phosphoserine (acyl2GroPSer) and L-alpha-1,2-diacyl-sn-glycero-3-phosphoinositol
      (acyl2GroPIns) compared to the microsomal membrane. The observed preference of
      NADPH-cytochrome reductase for acyl2GroPSer and acyl2GroPIns appeared not to be a
      result of the procedure for solubilisation and/or purification of the protein.
      The specific interaction of NADPH-cytochrome reductase with acyl2GroPSer and
      acyl2GroPIns was further investigated by comparison of the effect of acyl2GroPSer
      and acyl2GroPIns with that of acyl2GroPCho and acyl2GroPEtn on the 2-[3
      (diphenylhexatrienyl)propanoyl]-1-hexadecanoyl-sn-glycero-3- phosphocholine
      (DphPamGroPCho)-dependent quenching of the tryptophan fluorescence of purified
      NADPH-cytochrome reductase. The results demonstrate that the addition of
      acyl2GroPSer or acyl2GroPIns affects the DphPamGroPCho-dependent quenching of the
      tryptophan fluorescence in a manner significantly different from the addition of
      acyl2GroPCho or acyl2GroPEtn. The relatively larger DphPamGroPCho-induced
      quenching of the tryptophan fluorescence of NADPH-cytochrome reductase in the
      presence of acyl2GroPSer and acyl2GroPIns must result from a change in the
      conformation of NADPH-cytochrome reductase induced by the latter two lipids.
      Finally, the possible consequences of this special interaction of acyl2GroPSer
      and acyl2GroPIns with NADPH-cytochrome reductase on the kinetic characteristics
      of the cytochrome P450 system were studied using cytochrome-P450-IIB1-dependent O
      dealkylation of pentoxyresorufin as the model reaction. These studies demonstrate
      that a 1:1 mixture of acyl2GroPCho and acyl2GroPSer results in a significantly
      higher apparent maximum rate (V) of O-dealkylation than a 1:1 mixture of
      acyl2GroPCho and acyl2ProPEtn or acyl2GroPCho alone. This increase in the
      apparent V can be ascribed to an acyl2GroPSer-dependent improvement of the
      interaction of NADPH-cytochrome reductase with cytochrome P450. This improvement
      of the interaction of the proteins cannot, however, be exclusively ascribed to
      the negative charge of acyl2GroPSer, since the other negatively charged
      phospholipid investigated, namely acyl2GroPIns, resulted in a significant
      decrease in the apparent V.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8281921
TI  - Characterisation of high-affinity and low-affinity receptors for ciliary
      neurotrophic factor.
AB  - Ciliary neurotrophic factor (CNTF) supports the survival of a wide variety of
      neuronal cells in culture. To characterise the receptor(s) mediating the
      biological responses of CNTF we measured the binding of radiolabelled CNTF to
      chick sympathetic neurons and human neuroblastoma cells. Two distinct CNTF
      binding sites with high and low affinity for the ligand were identified by steady
      state binding experiments. Furthermore, two low-affinity binding sites could be
      discriminated on the basis of the dissociation rates. Cross-linking experiments
      showed that CNTF interacts with two proteins, one of 80 kDa and one of 140 kDa.
      The identity of the 80-kDa protein was determined by transient transfection
      experiments with the rat CNTF-binding protein CNTFR alpha while the properties of
      the 140-kDa protein correspond to those of gp130. Antisense experiments confirmed
      that CNTFR alpha is necessary for high affinity binding of 125I-CNTF and
      therefore a necessary subunit of the high-affinity receptor.

PMID- 8281922
TI  - Conformational differences between complexes of elongation factor Tu studied 19F
      NMR spectroscopy.
AB  - An analogue of elongation factor Tu (EF-Tu) from Escherichia coli was prepared by
      biosynthetic incorporation of 3-fluorotyrosine. The 19F-NMR spectra of the binary
      complexes of this protein with GDP, GTP and elongation factor Ts (EF-Ts) and the
      ternary complexes EF-Tu.GDP.aurodox and EF-Tu.GDP.EF-Ts were measured. EF-Tu
      contains ten tyrosine residues and all of the complexes studied gave complex 19F
      spectra with overlapping resonances. EF-Tu.GDP gave a spectrum in which two
      signals were markedly different from those shown by the other complexes, the two
      resonances being shifted downfield by at least 3.4 ppm and 0.9 ppm relative to
      their shifts in the other complexes. Such large downfield shifts can be explained
      by second-order electric field shielding effects resulting from these two
      tyrosine residues being in a sterically constrained environment in EF-Tu.GDP and
      with the steric restraints being released in all of the other complexes. The X
      ray diffraction structure of EF-Tu.GDP shows that Tyr87 in the N-terminal domain
      (domain I) and Tyr309 in the C-terminal domain (domain III) are both buried
      within the protein and are close to each other: these residues are in regions of
      EF-Tu previously implicated in the structural changes between EF-Tu.GDP and EF
      Tu.GTP by other workers. If these tyrosine residues correspond to the two
      downfield resonances of the spectra of EF-Tu.GDP, the results from the 19F-NMR
      would be consistent with these earlier indications that domain I interacts
      closely with domain III in EF-Tu.GDP and that the amino acids between Gly83 and
      Gly100 are an important part of this interaction. For all the other complexes
      studied, these tyrosines are in a less sterically crowded environment consistent
      with a weaker interaction between the two domains. The 19F-NMR spectrum of the
      trypsin-cleaved product of EF-Tu.GDP, from which the X-ray diffraction structural
      data have been obtained, shows no significant differences from the native protein
      so that trypsin cleavage causes no large changes in the protein's structure.

PMID- 8281923
TI  - Unfolding/refolding studies of the myosin rod.
AB  - The effect of guanidine hydrochloride on the gel-filtration chromatography,
      viscosity, far ultraviolet circular dichroism and fluorescence emission intensity
      of the myosin rod was studied under equilibrium conditions. The normalized
      transition curves for each of these methods were comparable with a midpoint at a
      guanidine hydrochloride concentration of 1.75-2 M. The curves were not, however,
      superposable, suggesting that the loss of helix content and the dissociation of
      the two chains of the myosin rod were not tightly linked. Furthermore, they were
      unexpectedly independent of the protein concentration over 0.05-20 microM. These
      phenomena are interpreted taking into account the large size of the molecule. A
      step-wise process is proposed as a model for the unfolding of the myosin rod.

PMID- 8281924
TI  - Monodehydroascorbate reductase activity in the surface membrane of leukemic
      cells. Characterization by a ferricyanide-driven redox cycle.
AB  - A transmembrane monodehydroascorbate reductase activity with a high affinity in
      the subpicomolar concentration range of the free radical can be measured at the
      surface of erythroleukemic cells using a ferricyanide-driven redox cycle. The
      activity is dependent on the membrane potential and can therefore only be found
      in intact cells. It is independent of the glutathione content of the cells.
      Thenoyltrifluoroacetone is an efficient inhibitor of the activity, whereas
      ouabain, monensin and tetraethylammonium show no effect. Cells are able to
      generate ascorbate from dehydroascorbic acid. This explains why both forms of
      vitamin C show practically the same affinity for the redox cycle but why it does
      not drive the redox cycle by itself because it is much slower and is not
      inhibited by thenoyltrifluoroacetone. The reductase activity is independent of
      the degree of differentiation of the leukemic cells.

PMID- 8281925
TI  - Glycogenolytic and antiglycogenolytic prostaglandin E2 actions in rat hepatocytes
      are mediated via different signalling pathways.
AB  - Prostaglandin E2 has been reported both to stimulate glycogen-phosphorylase
      activity (glycogenolytic effect) and to inhibit the glucagon-stimulated glycogen
      phosphorylase activity (antiglycogenolytic effect) in rat hepatocytes. It was the
      purpose of this study to resolve this apparent contradiction and to characterize
      the signalling pathways and receptor subtypes involved in the opposing
      prostaglandin E2 actions. Prostaglandin E2 (10 microM) increased glucose output,
      glycogen-phosphorylase activity and inositol trisphosphate formation in
      hepatocyte cell culture and/or suspension. In the same systems, prostaglandin E2
      decreased the glucagon-stimulated (1 nM) glycogen-phosphorylase activity and cAMP
      formation. The signalling pathway leading to the glycogenolytic effect of PGE2
      was interrupted by incubation of the hepatocytes with 4 beta-phorbol 12-myristate
      13-acetate (100 nM) for 10 min, while the antiglycogenolytic effect of
      prostaglandin E2 was not attenuated. The signalling pathway leading to the
      antiglycogenolytic effect of prostaglandin E2 was interrupted by an incubation of
      cultured hepatocytes with pertussis toxin (100 ng/ml) for 18 h, whereas the
      glycogenolytic effect of prostaglandin E2 was enhanced. The EP1/EP3 prostaglandin
      E2-receptor-specific prostaglandin E2 analogue Sulproston had a stronger
      glycogenolytic potency than the EP3 prostaglandin-E2-receptor-specific
      prostaglandin E2 analogue Misoprostol. The antiglycogenolytic potency of both
      agonists was equal. It is concluded that the glycogenolytic and the
      antiglycogenolytic effects of prostaglandin E2 are mediated via different
      signalling pathways in hepatocytes possibly involving EP1 and EP3 prostaglandin
      E2 receptors, respectively.

PMID- 8281926
TI  - Evidence for cAMP-independent thyrotropin effects on astroglial cells.
AB  - Thyroid hormones are essential for normal brain development and function. Brain
      astroglial cells express type II iodothyronine 5'-deiodinase which converts
      thyroxine into 3,5,3'-triiodothyronine. This type II deiodinase is regulated
      through various signalling pathways, allowing probably for the local adaptation
      of the level of 3,5,3'-triiodothyronine. Our results demonstrated that
      thyrotropin was able to induce type II deiodinase activity in astrocytes. A
      thyrotropin receptor was demonstrated. It was not coupled, as in thyroid, to
      adenylyl cyclase and phospholipase C, but it stimulated cytosolic phospholipase
      A2. The stimulation by thyrotropin of both thyroxine synthesis in thyroid and its
      local activation in astrocytes, could protect the brain from variations in the
      level of 3,5,3'-triiodothyronine.

PMID- 8281927
TI  - Evolution of pro-protamine P2 genes in primates.

PMID- 8281928
TI  - ATP synthesis in mitochondria.

PMID- 8281929
TI  - Control of sex determination in animals.

PMID- 8281930
TI  - The biochemistry of white and brown adipocytes analysed from a selection of
      proteins.

PMID- 8281931
TI  - Participation in cellular prostaglandin synthesis of type-II phospholipase A2
      secreted and anchored on cell-surface heparan sulfate proteoglycan.
AB  - Rat-liver-derived BRL-3A cells, which express both type-II phospholipase A2
      (PLA2) and cytosolic PLA2 (cPLA2), generated prostaglandin E2 (PGE2) in the
      presence of fetal calf serum. When the cells were treated with tumor necrosis
      factor (TNF), PGE2 generation was greatly stimulated. The production of PGE2
      observed in both cases was suppressed by a type-II PLA2-specific inhibitor,
      thielocin A1. Appreciable amounts of type-II PLA2 were released into the medium
      from the TNF-stimulated cells when heparin was added extracellularly. The release
      of type-II PLA2 from TNF-stimulated cells was also found in the presence of
      heparan sulfate or dextran sulfate, whereas other glycosaminoglycans showed no
      effects under the same conditions. These findings suggest that type-II PLA2
      expressed in BRL-3A cells mostly associates with the cell surface by binding to
      cellular heparan sulfate proteoglycan. Removal of cell-surface-associated type-II
      PLA2, by either extracellular addition of heparin or by prior treatment of the
      BRL-3A cells with heparitinases, resulted in marked reduction of PGE2 synthesis
      in the cells. Exposure of BRL-3A cells to thrombin also induced the apparent
      secretion of type-II PLA2, and thrombin-stimulated PGE2 generation was suppressed
      by heparin effectively. Type-II PLA2 secreted and attached to heparan sulfate on
      the cell surface may therefore play an essential role in PGE2 synthesis by BRL-3A
      cells.

PMID- 8281932
TI  - Insulin and tumor-promoting agent regulate an inhibitor of the 44-kDa mitogen
      activated protein kinase/extracellular signal-regulated protein kinase 1 in
      fibroblasts.
AB  - We have examined the negative regulation of the 44-kDa mitogen-activated protein
      kinase (MAP kinase), also known as extracellular signal-regulated protein kinase
      1 (ERK1), in NIH3T3 cells transfected with an expression plasmid encoding the
      human insulin receptor (NHIR cells). In these cells ERK1 activation is induced by
      two distinct stimuli, insulin and tumor-promoting agent (TPA). While insulin was
      found to be more potent than TPA for ERK1 activation, both stimuli produced the
      same transient activation pattern with a rapid peak (reached within 5 min)
      followed by a fast decrease within 20 min. By performing reconstitution
      experiments with immunoprecipitated ERK1 and lysates from NHIR cells, we showed
      that extracts from untreated cells exhibit an ERK1 inhibitory activity.
      Interestingly, this inhibitor was found to be regulated by insulin and TPA with a
      profile that is the mirror image of ERK1 activity. This repressing activity was
      sensitive to tyrosine phosphatase inhibitors, such as sodium orthovanadate and
      zinc acetate, but it was not affected by serine/threonine phosphatase inhibitors,
      such as sodium fluoride and okadaic acid. Moreover, it was possible to observe in
      extracts of NHIR cells an activity dephosphorylating ERK1. The time course of
      this phosphatase activity was comparable to that of the ERK1 inhibition,
      suggesting that the repressing activity could reflect a dephosphorylating action.
      Interestingly, phosphatase 2A treatment of extracts from 5-min TPA-treated cells
      (where the ERK1 inhibitor was weak) was able to induce an increase in the ERK1
      repressing activity. This suggests that serine/threonine dephosphorylation of
      ERK1 inhibitor leads to an increase in its activity. In summary, we have shown
      that NHIR cells contain a regulatable ERK1 inhibitor, which is likely to be due
      to tyrosine phosphatase(s). We would like to suggest that such activities are key
      components in the fine-tuning of the MAP kinase cascade.

PMID- 8281933
TI  - Two states of the nucleotide-binding site of sarcoplasmic reticulum adenosine
      triphosphatase detected by the calcium-dependent reaction with adenosine 5'
      [gamma-imidazolidate]triphosphate and adenosine 5'-[beta
      imidazolidate]diphosphate.
AB  - The Ca(2+)-ATPase from sarcoplasmic reticulum can be inhibited by adenosine 5'
      [gamma-imidazolidate]triphosphate through the formation of an intramolecular
      cross-link at the active site which is dependent on the presence of Ca2+ [Bill,
      E., Gutowski, Z. & Bamert, H.G. (1988). Calcium-dependent inactivation of the
      Ca(2+)-ATPase from sarcoplasmic reticulum by chemically reactive adenosine
      triphosphate, Eur. J. Biochem. 176, 119-124] In the present study we show that
      adenosine 5'-[beta-imidazolidate]diphosphate is likewise an inhibitor of the
      Ca(2+)-ATPase effecting a similar inhibition pattern on phosphate release and
      Ca2+ transport. The overall reaction is Ca2+ dependent and produces a protein
      band that in SDS/PAGE is indistinguishable from that seen with
      ATP[imidazolidate]. This shows that the side chain of Asp351 which is claimed to
      be involved in the cross-linking reaction must be in reach of both the beta and
      the gamma phosphate moiety of the respective nucleotides. The cross-linked
      product is formed by a two-step reaction. The first step is the fast reaction of
      nucleotide imidazolidate presumably at the phosphorylation site (Asp351) under
      formation of a mixed anhydride that covalently links nucleotide and protein.
      Subsequently, the nucleotide is released by a substitution reaction with a second
      amino acid side chain. This cross-linking reaction is strictly Ca2+ dependent
      and, remarkably, requires Ca2+ to be added before addition of the inhibitor. It
      proceeds at two rates and suggests that there are two states of the nucleotide
      bindings site. This is also supported by the fact that in the absence of CA2+,
      ATP[imidazolidate] reacts only in approximately 50% of the calculated ATP-binding
      sites (based on 80-90% ATPase of total sarcoplasmic reticulum protein) with no
      subsequent cross-linking reaction.

PMID- 8281934
TI  - A polymerising Root-effect fish hemoglobin with high subunit heterogeneity.
      Correlation with primary structure.
AB  - The blood of the teleost Chelodonichthys kumu, living in the temperate waters of
      New Zealand, contains a single hemoglobin. The complete amino acid sequence of
      the alpha and beta chain has been established. The presence of a reactive Cys in
      the external position beta CD8(49) causes polymerisation through intermolecular
      disulfide bridges between beta chains, with no alteration of functional features.
      C. kumu Root-effect hemoglobin displays very low or no subunit co-operativity in
      the physiological pH range. Kinetic experiments on the oxygen dissociation and
      binding of carbon monoxide show a marked, pH-dependent functional heterogeneity
      of the two chains, which contributes to the observed reduction of co-operativity.
      In contrast, kinetic heterogeneity was not observed in the process of CO
      dissociation, indicating that functional differences between the subunits are
      detectable only for the dynamic ligand association pathway. The allosteric
      effector, ATP, seems to increase the pKa of the proton-linked effect on the slow
      reacting subunit, affecting the quaternary equilibrium through stabilisation of
      the T state at lower pH, rather than enhancing the functional heterogeneity
      itself. In position E11 of both chains, Val (usually present at the distal side
      of the heme), is substituted by Ile. Although this residue has been shown not to
      significantly alter ligand binding to the alpha chain, to some extent it can
      perturb the access of oxygen to the beta chain. Thus, this substitution may be
      the main reason for subunit functional heterogeneity.

PMID- 8281935
TI  - A high-resolution solid-state 13C-NMR study on [1-13C]Ala and [3-13C]Ala and [1
      13C]Leu and Val-labelled bacteriorhodopsin. Conformation and dynamics of
      transmembrane helices, loops and termini, and hydration-induced conformational
      change.
AB  - We have recorded 100.7-MHz high-resolution solid-state 13C-NMR spectra of [3
      13C]Ala, [1-13C]Ala-labelled, Leu-labelled and Val-labelled bacteriorhodopsin
      (bR), to analyze the conformation and dynamics of transmembrane alpha helices and
      hydration-induced conformational changes. We assigned the 13C-NMR signals of
      these 13C-labelled amino acid residues to portions of the transmembrane alpha
      helices, loops and N-terminus and C-terminus, based on the conformation-dependent
      13C chemical shift. The assignment of peaks to the transmembrane alpha helices is
      straightforward in view of the characteristic 13C chemical shifts of the C beta
      and carbonyl carbons, referred to the data of the model system. The signals of
      the transmembrane alpha helices were further divided into three or four peaks
      which are ascribed to either a dispersion of torsion angles of the alpha helices
      or variation of environments around the helices. In addition, we found that
      conformation of the N-terminus and C-terminus of bR is virtually the random-coil
      form which undergoes rapid reorientational motion in the hydrated system.
      Further, we show that the higher-order (secondary and/or tertiary) structure of
      bR is influenced by the hydration/dehydration process of the purple membrane, as
      viewed from the peak profile of the Ala C beta 13C signals. This change of
      structure occurs between relative humidities of 2% and 4%, consistent with the
      shift of the absorption maxima of retinal, which arise from the
      protonation/deprotonation processes of the Schiff base. In contrast, no such
      change of the carbonyl signals occurs for the Leu, Val and Ala residues. For the
      latter two residues, some spectral changes were noted at the stage of full
      hydration.

PMID- 8281936
TI  - Investigation of intra-domain and inter-domain interactions of glutathione
      transferase P1-1 by limited chymotryptic cleavage.
AB  - Limited proteolysis of glutathione transferase P1-1 (GSTP1-1) by chymotrypsin
      performed at 20 degrees and 30 degrees C mainly generates two complementary
      peptides of 17 kDa and 6 kDa molecular mass with concomitant loss of catalytic
      capacity. Sequence analysis of these peptides showed that the peptide bond
      between Tyr47 and Gly48 was cleaved. The analysis of the recently resolved three
      dimensional structure of GSTP1-1 [Reinemer, P., Dirr, H. W., Ladenstein, R.,
      Huber, R., Lo Bello, M., Federici, G. & Parker, M. W. (1992) J. Mol. Biol. 227,
      214-226] suggests that the proteolytically cleaved bond results located in a
      portion of the polypeptide chain lining the G-site which has been demonstrated to
      be part of an exposed and flexible region of the N-terminal domain (structural
      elements alpha B1 and alpha B2) [Aceto, A., Caccuri, A. M., Sacchetta, P.,
      Bucciarelli, T., Dragani, B., Rosato, N., Federici, G. & Di Ilio, C. (1992)
      Biochem. J. 285, 241-245]. The fragments which are generated by proteolysis at 20
      degrees C, remain linked by noncovalent interaction in a complex (nicked GSTP1-1)
      which is dissociated by incubation at higher temperatures. As shown by circular
      dichroic analysis, although inactive, nicked GSTP1-1 retains an overall secondary
      structure closely resembling that of the parent enzyme. However, the fluorescence
      data of the nicked GSTP1-1 indicate that the Trp38, which is near the
      chymotrypsin-cleavable bond, becomes exposed in a more polar environment. This
      indicates that, in the nicked enzyme, the polypeptide portion containing the
      structural elements alpha B1 and alpha B2 has more freedom of fluctuation. The
      fact that this polypeptide chain portion contains two essential amino acid
      residues of the G-site (Trp38 and Lys42) might account for the loss of ability to
      bind glutathione by the nicked enzyme which is consequently catalytically
      inactive. Proteolysis performed at 30 degrees C generated a homodimeric 17-kDa
      fragment. The structural analysis of this fragment suggests that the GSTP1-1
      alpha C helix, which is located in the domain I and is thought to be involved in
      the inter-domain interaction, could exert a critical role in maintaining the
      native folding of domain II.

PMID- 8281937
TI  - 1H-NMR studies and secondary structure of the RGD-containing snake toxin,
      albolabrin.
AB  - Albolabrin is a naturally occurring peptide from snake venom containing the
      sequence Arg-Gly-Asp (RGD). It inhibits platelet aggregation by blocking the
      binding of fibrinogen to the glycoprotein Gp IIb-IIIa, on the surface of
      activated platelets. Albolabrin consists of 73 residues with six intramolecular
      disulphide bonds. The 1H-NMR spectrum of albolabrin has been assigned using
      homonuclear two-dimensional techniques and its secondary structure determined.
      Like kistrin and echistatin, two related peptides from snake venom, albolabrin
      appears to have little regular secondary structure in solution. Several bends and
      two short distorted beta sheets are observed. The RGD sequence, important for
      binding to the receptor, lies in a mobile loop joining two strands of one of
      these beta sheets. This loop undergoes a pH-dependent conformational change.

PMID- 8281938
TI  - Evidence that the reaction of the UDP-N-acetylglucosamine 1
      carboxyvinyltransferase proceeds through the O-phosphothioketal of pyruvic acid
      bound to Cys115 of the enzyme.
AB  - The enzyme UDP-N-acetylglucosamine 1-carboxyvinyltransferase
      (enolpyruvyltransferase, EC 2.5.1.7) catalyses the transfer of the intact 1
      carboxyvinyl moiety of phosphoenolpyruvate to the 3'-hydroxyl group of the
      glucosamine moiety of UDP-(2')-N-acetylglucosamine with the concomitant release
      of inorganic phosphate, the first committed step in the biosynthesis of the
      bacterial cell wall peptidoglycan. Overexpression of the enzyme from Enterobacter
      cloacae in Escherichia coli allowed the isolation of large amounts of purified
      enzyme (approx. 900 mg/20 g fresh mass bacteria). By incubating the enzyme with
      14C-labelled phosphoenolpyruvate, 32P-labelled orthophosphate and unlabelled UDP
      (2')-N-acetyl-(3')-1-carboxyvinylglucosamine, we were able to isolate and
      characterise a reaction intermediate, covalently bound to the protein. It
      contains stoichiometric quantities of the C3 moiety (0.98 mol/mol) as well as of
      the phosphate moiety (0.95 mol/mol) of phosphoenolpyruvate relative to protein.
      The rapid turnover of this protein-bound intermediate in the presence of UDP-(2')
      N-acetylglucosamine towards the product UDP-(2')-N-acetyl-(3')-1
      carboxyvinylglucosamine suggests that the intermediate is kinetically competent.
      We also present evidence that the intermediate is bound as the O-phosphothioketal
      of pyruvic acid to Cys115 of the enzyme. This is the same Cys residue to which
      phosphomycin, an irreversible inhibitor of the UDP-GlcNAc
      carboxyvinyltransferase, binds covalently. Exchange of Cys115 for a Ser residue
      resulted in an inactive enzyme, demonstrating the essential role of Cys115 for
      the reaction. The only other enzyme known to catalyse the transfer of the intact
      1-carboxyvinyl moiety of phosphoenolpyruvate to a substrate is the 3
      phosphoshikimate 1-carboxyvinyltransferase (EC 2.5.1.19), the sixth enzyme of the
      shikimate pathway. The reaction of this synthase is known to proceed through a
      single, tightly but not covalently bound, tetrahedral intermediate. Even though
      the two enzymes share similarities in their primary amino acid sequences, their
      reaction mechanisms appear to be substantially different.

PMID- 8281939
TI  - A plasma membrane 'vacuum cleaner' for daunorubicin in non-P-glycoprotein
      multidrug-resistant SW-1573 human non-small cell lung carcinoma cells. A study
      using fluorescence resonance energy transfer.
AB  - A multidrug resistant (MDR) human non-small cell lung carcinoma cell line, SW
      1573/2R120 (2R120), not containing the drug-efflux pump P-glycoprotein (PgP), has
      been studied for the transport of daunorubicin (DN) across the cellular plasma
      membrane. Earlier, reduced initial DN-uptake rates and lower cellular DN steady
      state concentrations were found for this cell line, when it was compared to the
      SW-1573 wild-type cell line. This finding was an indication for the presence of
      another cellular drug-efflux pump. However, we found similar DN-efflux rates in
      drug-free medium for the two cell lines, while for Pgp-containing MDR SW
      1573/2R160 (2R160) cells the efflux rate was increased compared to wild-type
      cells. In order to elucidate differences in DN transport across the cellular
      plasma membrane, the association of DN with plasma membranes of intact cells was
      investigated, using fluorescence-resonance-energy transfer. For this purpose, the
      plasma-membrane probe 1-(4-trimethyl-ammoniumphenyl)-6-phenyl-1,3,5-hexatriene
      (TMA-DPH) was chosen since, because of the overlap between the emission spectrum
      of TMA-DPH and the excitation spectrum of DN, transfer of energy can be achieved
      from TMA-DPH to DN. Cells were loaded with TMA-DPH and, after addition of 10
      microM DN, the TMA-DPH fluorescence was quenched. Rapid initial quenching proved
      to be similar in the MDR 2R160 (Pgp-containing) cells and in the SW-1573 wild
      type cells (21 +/- 1% and 20 +/- 2%, respectively), but was less in the MDR 2R120
      cells not containing Pgp (14 +/- 1%). This finding correlated with a lowered
      amount of DN dissolved in the plasma membrane of 2R120 cells. We interpret these
      data to be the result of a 'vacuum-cleaner' pumping system other than Pgp which
      removes DN from a plasma membrane compartment and equilibrates relatively slowly
      with the interior of the cell.

PMID- 8281940
TI  - Insulin-like growth factor-1 modulates steroid hormone effects on osteocalcin
      synthesis in human MG-63 osteosarcoma cells.
AB  - The 1,25-dihydroxyvitamin-D3-(calcitriol)-induced medium osteocalcin and cellular
      osteocalcin mRNA concentrations are increased in a dose-dependent and time
      dependent manner by prior treatment of the human MG-63 osteosarcoma cells with
      insulin-like growth factor-I (IGF-I). In addition, IGF-I reverses the inhibitory
      effects of dexamethasone and enhances the effects of retinoic acid on osteocalcin
      synthesis. The stimulatory effect of IGF-I on osteocalcin synthesis is
      accompanied by stabilization of osteocalcin mRNA and a decrease of AP-1 binding
      to the osteocalcin promoter. The binding of the vitamin-D receptor (VDR) to its
      cognate response element is not affected by IGF-I. In contrast to its effects on
      osteocalcin synthesis, both baseline and calcitriol-stimulated alkaline
      phosphatase activities are decreased by IGF-I treatment. Furthermore, IGF-I has
      mitogenic effects on MG-63 cells. The proliferation of the cells and the levels
      of c-jun mRNA are greatly increased during IGF-I treatment. Calcitriol reduces or
      eliminates both these effects. The low concentrations of IGF-I used in this study
      suggest that IGF-I is an important normal regulator of the synthesis of
      osteocalcin, a bone calcium-binding protein participating in bone mineralization,
      by modulating the effects of steroid hormones on its synthesis.

PMID- 8281941
TI  - Sequence of pig lens aldose reductase and electrospray mass spectrometry of non
      covalent and covalent complexes.
AB  - The complete sequence of pig lens aldose reductase (EC 1.1.1.21), a member of the
      nicotinamide coenzyme-dependent aldo-keto reductase super family, was determined
      by the combined use of data obtained from Edman degradation, fast-atom
      bombardment mass spectrometry and electrospray mass spectrometry. The N-terminal
      residue of human and pig aldose reductase was shown to be acetylated. The
      assignment of a disulfide bridge (Cys298-Cys303) was obtained by mass
      spectrometry. Electrospray mass spectrometry has been used for molecular mass
      measurement of human muscle (35758 +/- 7 Da) and pig lens (35778 +/- 3Da) aldose
      reductase; using mild ionization conditions, it has also been used to study the
      reversible interaction involved in a non-covalent complex with NADP+ (36527 +/-
      4Da). An alkylating analog of NADP+ (3-chloroacetylpyridine-adenine dinucleotide
      phosphate) was used as an irreversible inhibitor to investigate the NADP binding
      site and the mass of the covalent complex was measured (36521 +/- 3 Da).

PMID- 8281942
TI  - The mature form of imported mitochondrial proteins undergoes conformational
      changes upon binding to isolated mitochondria.
AB  - Mature mitochondrial proteins (aspartate aminotransferase, malate dehydrogenase,
      hydroxyacyl coenzyme A dehydrogenase, creatine kinase) and cytosolic proteins
      (aldolase, glyceraldehyde-3-phosphate dehydrogenase) with a basic pI were found
      to bind to isolated mitochondria, electrostatic interactions being mainly
      responsible for their binding. Mitochondrial aspartate aminotransferase bound
      with a Kd' of 30 nM in 0.6 M sorbitol, 20 mM Hepes/KOH, pH 7.4, at 25 degrees C.
      Cytosolic aspartate aminotransferase and glutamate dehydrogenase (a protein
      located in the mitochondrial matrix) both with an acidic pI, did not bind to
      mitochondria. Treatment of mitochondria with proteinases did not affect the
      subsequent binding of imported mitochondrial proteins. Their association with
      both intact and proteinase-treated mitochondria resulted in a marked increase in
      their susceptibility toward proteinase K. In contrast, the basic cytosolic
      proteins tested bound only to intact mitochondria and thereby did not become more
      susceptible toward proteolytic attack. Treatment of mitochondria with adriamycin,
      a drug binding to acidic phospholipids, prevented the subsequent association of
      mitochondrial aspartate aminotransferase with mitochondria and the ensuing
      conformational labilization. Apparently, the mature moiety of imported
      mitochondrial proteins is partially unfolded upon interaction with the lipid
      component of the mitochondrial envelope. Both the binding of the mitochondrial
      proteins and their conformational labilization is independent of ATP and the
      electrochemical potential across the inner membrane.

PMID- 8281943
TI  - The actin/actin interactions involving the N-terminus of the DNase-I-binding loop
      are crucial for stabilization of the actin filament.
AB  - Actin can be specifically cleaved between residues 42 and 43 with a novel
      protease from Escherichia coli A2 strain (ECP) [Khaitlina, S. Y., Collins, J. H.,
      Kuznetsova, I.M., Pershina, V.P., Synakevich, I.G., Turoverov, K.K. & Usmanova,
      A.M. (1991) FEBS Lett. 279, 49-51]. The resulting C-terminal and N-terminal
      fragments remained associated to one another in the presence of either Ca2+ or
      Mg2+. The protease-treated actin was, however, neither able to spontaneously
      assemble into filaments nor to copolymerize with intact actin unless its tightly
      bound Ca2+ was replaced with Mg2+. Substitution of Mg2+ for the bound Ca2+ was
      also necessary to partially restore the ability of the protease-treated actin to
      inhibit the DNase I activity. The critical concentration for KCl-induced
      polymerization of ECP-treated ATP-Mg-G-actin, determined by measuring the
      fluorescence of pyrenyl label, was approximately threefold higher than that for
      actin cleaved between residues 47 and 48 using subtilisin, and 36-fold higher
      than the critical concentration for polymerization of intact actin under the same
      conditions. Morphologically, the filaments of ECP-treated actin were
      indistinguishable from those of intact actin. Comparison of the fluorescence
      spectra of pyrenyl-labelled actins and chemical cross-linking with N,N'-1,2
      phenylenebismaleimide have, however, revealed structural differences between the
      filaments assembled from ECP-treated actin and those of intact as well as
      subtilisin-treated actin. Moreover, the filaments of ECP-treated actin were
      easily disrupted by centrifugal forces or shearing stress unless they were
      stabilized by phalloidin. The results are consistent with the direct
      participation of the region around residues 42 and 43 in the monomer/monomer
      interactions as predicted from the atomic model of F-actin [Holmes, K.C., Popp,
      D., Gebhard, W. & Kabsch, W. (1990) Nature 347, 44-49] and suggest that the
      interactions involving this region are of primary importance for stabilization of
      the actin filament. The mechanism of the regulation of actin polymerization by
      the tightly bound divalent cation is also discussed.

PMID- 8281944
TI  - Structural and physico-chemical characteristics of Bordetella pertussis adenylate
      kinase, a tryptophan-containing enzyme.
AB  - The adk gene from the Gram-negative pathogen Bordetella pertussis was cloned by
      complementing the thermosensitive Escherichia coli adk strain CR341T28. B.
      pertussis adenylate kinase is a 218-amino-acid protein that has high similarity
      with adenylate kinase from Escherichia coli and Hemophilus influenzae (57%). A
      distinct characteristic of enzyme from B. pertussis, not found in other bacterial
      adenylate kinases, is the presence of a tryptophan residue at position 185.
      Although distant from the catalytic site, this single tryptophan serves as a
      convenient probe for monitoring the binding of nucleotide substrates or analogs
      to the enzyme. Differential scanning calorimetry and equilibrium unfolding
      experiments in guanidine.HCl indicate similar stabilities for adenylate kinase
      from B. pertussis and E. coli. An extensive comparison between physico-chemical
      properties of adenylate kinase from B. pertussis and the enzyme from E. coli
      showed that the kinetic and structural properties of the two enzymes are very
      similar. However, infrared spectroscopy has allowed to identify small but
      significant differences in the secondary structure of the two proteins.

PMID- 8281945
TI  - Hexadecylpalmitoylglycerol or ceramide is linked to similar glycophosphoinositol
      anchor-like structures in Trypanosoma cruzi.
AB  - The lipopeptidophosphoglycan from Trypanosoma cruzi is a glycosylated inositol
      phosphoceramide isolated from epimastigotes at the stationary phase of growth (4
      5 days). We have now purified two similar glycoinositolphospholipids
      (glycoinositolphospholipid A and glycoinositolphospholipid B) from epimastigotes
      after the second day of culture growth. [3H]Palmitic acid was incorporated into 1
      O-hexadecyl-2-O-palmitoylglycerol in glycoinositolphospholipid A and into
      ceramide in glycoinositolphospholipid B. The lipids were released by incubation
      with glycosylphosphatidylinositol-specific phospholipase C from Bacillus
      thuringiensis or by chemical methods. After alkaline hydrolysis, the lipids were
      analysed by GLC/MS. In glycoinositolphospholipid A the resulting lipids
      corresponded to 1-O-hexadecylglycerol and palmitic acid. The ceramide components
      in glycoinositolphospholipid B are sphinganine, palmitic acid and lignoceric
      acid. The oligosaccharides could be degraded by nitrous acid and further enzymic
      treatment showed that the two glycoinositolphospholipids isolated from T. cruzi
      share the common core structure of the glycosylphosphatidylinositol membrane
      anchors. The microheterogeneity was determined, as well as the substitution by
      galactose, and was mainly in the furanose configuration as was previously
      described for lipopeptidophosphoglycan. However, methylation analysis indicated
      that 20% of the galactose is in the pyranose form. Both
      glycoinositolphospholipids mainly differ in the lipid moiety.

PMID- 8281946
TI  - Formation of a functionally active sodium-translocating hybrid F1F0 ATPase in
      Escherichia coli by homologous recombination.
AB  - A deletion mutant of Escherichia coli lacking the genes for ATPase subunits a, c,
      b, delta and part of the alpha subunit was transformed with a plasmid containing
      the corresponding genes of the sodium-translocating ATPase of Propionigenium
      modestum. The respective DNA fragment of P. modestum was integrated into the
      genome of the E. coli deletion mutant by site-specific homologous recombination.
      The sites of this recombination event were identified by cloning and DNA
      sequencing. As a consequence of the recombination event, a functionally active
      hybrid ATPase was obtained by in vivo complementation. The biochemical
      characterization of this hybrid ATPase revealed high sensitivity to
      dicyclohexylcarbodiimide as well as strong activation by the addition of sodium
      ions. After reconstitution into liposomes, the hybrid ATPase catalysed the
      transport of Na+ upon ATP addition. In the absence of Na+, the ATPase hybrid was
      able to pump protons, as was shown by the ATP-dependent fluorescence quenching of
      9-amino-6-chloro-2-methoxyacridine.

PMID- 8281947
TI  - The expression of human plasma cholesteryl-ester-transfer protein in HepG2 cells
      is induced by sodium butyrate. Quantification of low mRNA levels by polymerase
      chain reaction.
AB  - Although human plasma cholesteryl-ester-transfer protein (CETP) is primarily
      synthesized in the liver, its expression in a number of transformed liver cell
      lines is very low. However the use of the human hepatoma cell line HepG2 as a
      model system for the regulation of CETP on mRNA level is facilitated by a
      quantitative reverse-transcribed polymerase chain reaction. We demonstrate a time
      dependent and concentration-dependent 3-4-fold induction of CETP mRNA by sodium
      butyrate. CETP mass in the medium is also augmented; however, the effect on
      protein level is less pronounced.

PMID- 8281948
TI  - Basal Mg(2+)-dependent ATPase activity of rat liver microsomes is not influenced
      by ambient free Ca2+.
AB  - The potent inhibitor of Ca2+, Mg(2+)-ATPase activity, thapsigargin, has been used
      to investigate the effect of ambient free Ca2+ on basal Mg(2+)-dependent ATPase
      activity in rat liver microsomes. Thapsigargin non-competitively inhibited both
      Ca(2+)-stimulated ATP-dependent Ca2+ uptake and Ca(2+)-stimulated Mg(2+)
      dependent ATPase activity. At a concentration of 1 microM, thapsigargin
      completely inhibited the Ca(2+)-pump activity, without affecting Mg(2+)-dependent
      ATPase activity measured in the absence of Ca2+. Increasing the ambient free Ca2+
      concentration did not alter the basal Mg(2+)-dependent ATPase activity. The data
      presented indicate that ATPase activity measured in the absence of Ca2+ is a
      reliable measure for the basal Mg(2+)-dependent ATPase activity and that,
      consequently, the Ca(2+)-stimulated Mg(2+)-dependent ATPase activity can indeed
      be defined as the difference between the ATPase activity measured in the presence
      and the absence of Ca2+.

PMID- 8281949
TI  - Flavin dynamics in oxidized Clostridium beijerinckii flavodoxin as assessed by
      time-resolved polarized fluorescence.
AB  - The time-resolved fluorescence characteristics of flavin in oxidized flavodoxin
      isolated from the anaerobic bacterium Clostridium beijerinckii have been
      examined. The fluorescence intensity decays were analyzed using the maximum
      entropy method. It is demonstrated that there exist large differences in
      fluorescence behaviour between free and protein-bound FMN. Three fluorescence
      lifetime components are found in oxidized flavodoxin, two of which are not
      present in the fluorescence-intensity decay of free FMN. The main component is
      distributed at 30 ps, with relative contribution of 90%. Another minor component
      (4% contribution) is distributed at 0.5 ns. The third component is distributed at
      4.8 ns (6%), coinciding with the main distribution present in the fluorescence
      decay of free FMN. The results allowed us to determine the dissociation constant,
      Kd = 2.61 x 10(-10) M (at 20 degrees C). Collisional fluorescence-quenching
      experiments revealed that the flavin moiety responsible for the longest
      fluorescence lifetime is, at least partially, exposed to the solvent. The
      shortest lifetime is not affected significantly, indicating that it possibly
      originates from an active-site conformation in which the flavin is more or less
      buried in the protein and not accessible to iodide. The fluorescence anisotropy
      behaviour of free and protein-bound FMN was examined and analyzed with the
      maximum-entropy method. It was found that an excess of apoflavodoxin is required
      to detect differences between free and protein-bound FMN. In free FMN one single
      distribution of rotational correlation times is detected, whereas in flavodoxin
      the anisotropy decay is composed of more than one distribution. Associative
      analysis of fluorescence anisotropy decays shows that part of the 4.8 ns
      fluorescence lifetime present in the flavodoxin fluorescence decay, is coupled to
      a rotational correlation time similar to that of free FMN in solution, while
      another part of this lifetime is coupled to a longer correlation time of about 1
      ns. This finding is in accordance with earlier studies [Barman, B. G. & Tollin,
      G. (1972) Biochemistry 11, 4746-4754] in which it was proposed that the first
      binding step of the flavin to the protein involves the phosphate group rather
      than another part of the FMN. The two shortest fluorescence lifetimes, which do
      not carry information on the long-term rotational behaviour of the protein, seem
      nonetheless to be associated with a longer rotational correlation time which is
      comparable to overall protein tumbling. These lifetime components probably
      originate from a complex in which the flavin-ring system is more or less
      immobilized within the protein matrix.

PMID- 8281950
TI  - Overproduction, purification and characterization of the Escherichia coli
      ferritin.
AB  - Recent studies have indicated that Escherichia coli possesses at least two iron
      storage proteins, the haem-containing bacterioferritin and ferritin. The ferritin
      protein has been amplified 600-fold to 11-14% of total cell protein in a bfr
      mutant and purified to homogeneity with an overall yield of 13%. The cellular
      ferritin content remained relatively constant throughout the growth cycle and
      amplification was accompanied by a 2.5-fold increase in cellular iron content.
      The isolated ferritin contained 5-20 non-haem iron atoms/holomer and resembled
      the eukaryotic ferritins rather than the prokaryotic bacterioferritins in
      containing no haem. The 24 subunits of this ferritin (M(r) 19,400) assemble into
      a spherical protein shell (12 +/- 1 nm diameter, M(r) 465,000) which sequesters
      at least 2000 iron atoms in vitro to form an electron-dense iron core of 7.9 +/-
      1 nm diameter. Electron-microscopic and Mossbauer spectroscopic studies with iron
      loaded ferritin showed that the core can be either crystalline (ferrihydrite) or
      amorphous, depending on the absence or presence of phosphate, respectively.
      Mossbauer spectroscopy with intact E. coli revealed a novel-high spin Fe(II)
      component which is enhanced in bacteria amplified for ferritin but not in the
      parental strain. Western blotting showed that ferritin and bacterioferritin are
      immunologically distinct proteins. E. coli is thus an organism containing both a
      ferritin and a bacterioferritin and the relative roles of the two iron-storage
      proteins are discussed in this study.

PMID- 8281951
TI  - Aromatization of 4-oxocyclohexanecarboxylic acid to 4-hydroxybenzoic acid by two
      distinctive desaturases from Corynebacterium cyclohexanicum. Properties of two
      desaturases.
AB  - We have previously demonstrated that Corynebacterium cyclohexanicum degrades
      cyclohexanecarboxylic acid, a bacteriocide, through a pathway including the
      aromatization of 4-oxocyclohexanecarboxylic acid to 4-hydroxybenzoic acid
      [Kaneda, T. (1974) Biochem. Biophys. Res. Commun. 58, 140-144]. Aromatization has
      now been shown to be catalysed by two desaturase enzymes. Under the action of
      desaturase I, 4-oxocyclohexanecarboxylic acid is converted to (+)-4-oxocyclohex-2
      enecarboxylic acid which is then aromatized by desaturase II to 4-hydroxybenzoic
      acid. The latter reaction is presumed to occur via the unstable intermediate, 4
      oxocyclohex-2,5-dienecarboxylic acid, which is spontaneously isomerized to 4
      hydroxybenzoic acid. Desaturase I has been purified in an electrophoretically
      homogeneous form. It is monomeric with a molecular mass of 67 kDa and contains
      one tryptophan, one histidine and two cysteine residues per enzyme molecule. The
      enzyme produces an equivalent amount of 4-oxocyclohex-2-enecarboxylic acid and
      hydrogen peroxide from 4-oxocyclohexanecarboxylic acid. The properties of
      desaturase I have been studied in detail. Desaturase II is unstable and has been
      partially purified. Its characterization is therefore limited. However, the
      molecular mass of desaturase II was estimated to be 43 kDa by gel filtration
      chromatography. The characterization of both desaturase enzymes is described in
      this paper. The possible environmental importance of microbial aromatization in
      the biodegradation of compounds with the cyclohexane structure is discussed.

PMID- 8281952
TI  - Treatment of left ventricular hypertrophy in hypertensive patients.
AB  - Left ventricular hypertrophy (LVH), as detected by electrocardiography or
      echocardiography, constitutes a powerful risk factor for cardiovascular morbidity
      and mortality. Antihypertensive drugs that modulate the sympathetic or renin
      angiotensin-aldosterone systems or the intracellular free Ca concentration (i.e.
      beta-blockers, postsynaptic alpha 1-blockers, centrally acting adrenergic drugs,
      calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors) can
      prevent or cause regression of LV mass after short-term therapy, this effect
      being more pronounced with ACE inhibitors. Diuretics and arterial vasodilators
      also cause regression of LVH provided that they are used for long enough to
      effect long-term control of arterial pressure. However, clinical studies also
      indicate that despite their equipotent blood-pressure lowering effects, there are
      marked differences not only in the ability of the different types of
      antihypertensive drugs to prevent or reverse LV mass but also within the same
      class of pharmacological drugs. Decreased LV mass in hypertensive patients may be
      associated with an improvement in diastolic function and has not been found to
      produce adverse effects on LV systolic performance.

PMID- 8281953
TI  - Functional and organic components of diastolic dysfunction in hypertensive heart
      disease: therapeutic implications.
AB  - The major structural and functional determinants of impaired left ventricular
      diastolic function in the hypertensive patient are reviewed, together with the
      indices normally used to detect this failure. The alteration of functional
      determinants can be quickly modified, while structural determinants are modified
      only over the long term. Drug therapy first affects the functional determinants,
      bringing about their attenuation and initiating the modification of the
      structural factors, thus accounting for the improvement in diastolic function
      over the long term.

PMID- 8281954
TI  - Regional myocardial ischaemia and diastolic dysfunction in hypertensive heart
      disease.
AB  - In patients with systemic hypertension there is progressive left ventricular
      remodelling characterized mainly by left ventricular hypertrophy accompanied by
      abnormal diastolic ventricular function. Regional ischaemia, secondary to
      abnormal myocardial perfusion may explain in part the decrease in relaxation and
      compliance of the hypertrophied left ventricle. Treatment with anti-ischaemia
      drugs, such as beta-blockers or calcium channel blockers, improve left
      ventricular diastolic function.

PMID- 8281955
TI  - Alterations in the extracellular matrix of the myocardium in essential
      hypertension.
AB  - Hypertension produces myocyte hypertrophy and increases the extracellular matrix.
      In order to determine the composition of the extracellular matrix we studied the
      hearts from 14 hypertensive patients by immunohistochemistry using antibodies
      against collagen I, III, IV and V, fibronectin, myoglobin, muscular specific
      actin, Factor VIII, CD 34 and vimentin. The myocardium showed a focal increase in
      fibronectin, collagen I and III and diffuse deposition of laminin, collagen IV
      and V. Cells positive for vimentin, Factor VIII and CD 34 were also increased,
      but with considerable variation from case to case. We found no relation between
      matrix variation and the degree of hypertension or the time elapsed from the
      beginning of the disease. We conclude that the main role of the matrix in
      hypertension may be remodelling of the heart so that it entraps muscle fibres and
      increases their contractility.

PMID- 8281956
TI  - Left ventricular hypertrophy in post-myocardial infarction left ventricular
      remodelling and in hypertension; similarities and contrasts.
AB  - Hypertensive left ventricular (LV) hypertrophy and post-myocardial infarction
      (MI) LV remodelling account for most of the clinically significant cases of LV
      hypertrophy presenting to a clinician. The clinical outcome of patients with
      concentric LV hypertrophy is known to be poor. However, it has not been widely
      recognized that post-MI LV remodelling is also dependent on wall stress-driven
      segmental LV hypertrophy. This review focuses on the similarities shared by these
      two related processes. The results of large scale clinical trials directed at
      these two processes is also discussed.

PMID- 8281957
TI  - Basic mechanisms of cardiac gene expression.
AB  - Although the physiological properties of the myocardium and their dynamic
      character have been the focus of intense research during the past three decades,
      the biochemical and molecular correlates underlying cardiac development and
      performance have, until recently, remained poorly understood. The development of
      modern biology has provided the necessary tools to undertake the study of the
      mechanisms involved in cardiac development and to understand the basis for
      important clinical and experimental problems in cardiovascular physiology. Most
      of the gene encoding contractile proteins have been cloned and characterized. The
      availability of molecular probes and the ability to introduce genes into
      individual cell types and tissues of living animals are the most important
      breakthroughs of molecular and cell biology. This permits not only analysis of
      basic mechanisms of gene expression but has also significant practical
      applications for gene therapy. It is now possible to analyse the role of
      different regulatory gene sequences and identify their corresponding transactive
      factors. In addition direct gene injection makes it possible to study gene
      expression in a natural context, under conditions that are physiologically
      relevant and controllable.

PMID- 8281958
TI  - Global and regional ischaemia in left ventricular hypertrophy reactive to
      hypertension.
AB  - Hypertension has two main effects on the heart; it increases afterload, causing
      left ventricular hypertrophy, and precipitates the risk factor for coronary
      atherosclerosis. Left ventricular hypertrophy is an independent risk factor, but
      hypertension is a clustering of cardiovascular risks with many metabolic
      abnormalities, one of which is the recently described endocrinological Syndrome X
      (hyperinsulinaemia, resistance to insulin-stimulated glucose uptake, glucose
      intolerance, high triglyceride levels, low HDL and hypertension, which is
      apparently unrelated to the cardiological Syndrome X (angina with normal coronary
      arteries). However, the link between both Syndromes X may be the derangement of
      microvasculture, particularly endothelial dysfunction of nitric oxide (NO)
      production.

PMID- 8281959
TI  - Segmentary coronary reserve in hypertensive patients with echocardiographic left
      ventricular hypertrophy, gamma-graphic ischaemia and normal coronary angiography.
AB  - Stress thallium scintigraphies are frequently positive in patients with systemic
      hypertension (SHT), especially in the presence of left ventricular hypertrophy
      (LVH). In order to determine whether positive thallium perfusion scans in
      patients with LVH secondary to SHT and normal coronary angiographies are due to
      segmentary reduction of coronary reserve (CR), we have studied 10 out of 60
      consecutive cases of SHT with echocardiographic LVH, using intracoronary Doppler.
      We compared coronary blood flow velocity at rest and post-papaverine (PP), and CR
      in at least two major coronary vessels, always including the one corresponding to
      the ischaemic segment. In the vessel with the least CR at rest, a new
      determination of CR was made under intracoronary nitroglycerin. A group of five
      normal patients acted as controls. The mean CR of the controls and patients,
      respectively, was 6.2 +/- 1.4 vs 2.7 +/- 0.9 (P < 0.001). In patients with
      positive thallium perfusion scans, the coronary arteries corresponding to the
      ischaemic segments had less CR (2.5 +/- 0.6) than arteries from non-ischaemic
      segments (3.4 +/- 1, P < 0.05). These differences were greater when the ischaemia
      was anterior. There was no correlation either between CR and left ventricular
      mass (r = 0.23) or rest coronary blood flow velocity (r = 0.07). Only one patient
      exhibited functional behaviour indicating reduced CR; this rose from 1.9 to 7.5
      after nitroglycerin 300 micrograms. In conclusion, CR determined by intracoronary
      Doppler and papaverine shows segmentary differences both in normal patients and
      in patients with LVH and normal coronary angiograms. This could be the cause of
      segmental ischaemia detected by means of radionuclide stress tests.

PMID- 8281960
TI  - Myocardial ischaemia in the hypertensive patient--the role of coronary
      microcirculation abnormalities.
AB  - Clinicians have long suspected that hypertrophied hearts have an inadequate
      coronary circulation. This clinical suspicion resulted from the observation that
      a large proportion of patients with left ventricular hypertrophy who have normal
      coronary arteriograms complain of angina and have ischaemia-like ST segment
      depression during effort. Hypertension is a known risk factor for the development
      of coronary artery disease and therefore the presence of angina in a patient with
      systemic hypertension is usually attributed to obstructive atherosclerotic
      coronary artery disease. However, angina may occur in hypertensive patients in
      the absence of coronary stenosis. A limitation of coronary flow reserve is
      responsible for signs and symptoms of myocardial ischaemia in many of these
      patients. This article will focus on the role of the coronary microcirculation in
      the genesis of ischaemia in patients with systemic hypertension who have no
      obstructive coronary artery disease. It will also briefly discuss other
      mechanisms potentially responsible for the angina syndrome in patients who have
      left ventricular hypertrophy but angiographically normal coronary arteries.

PMID- 8281962
TI  - Role of the cardiac renin-angiotensin system in hypertensive cardiac hypertrophy.
AB  - The unique efficacy of converting-enzyme inhibitors in inducing regression, or
      preventing the occurrence, of ventricular hypertrophy associated with systemic
      hypertension has for many years pointed to a possible direct effect of the renin
      angiotensin system in the pathogenesis of cardiac hypertrophy. Over the last 10
      years evidence has been forthcoming about direct trophic effects of angiotensin
      II in several experimental systems, and we now have conclusive evidence for the
      existence of a local, intracardiac renin-angiotensin system. This system is
      capable of local synthesis of all components of the renin-angiotensin system, and
      has been demonstrated to be capable to cleave, via the classic pathway,
      angiotensin peptides from the precursor, angiotensinogen. Moreover, a number of
      studies have demonstrated the capacity of regulatory response and modulation of
      activity of the local system in response to a variety of pharmacological
      perturbations, and differential regulation of expression of specific components
      under pathological conditions. There is, thus, fairly solid evidence for
      participation of the cardiac renin-angiotensin system in the pathogenesis of
      hypertensive cardiac hypertrophy. Whether this participation is causative in
      character, or only a secondary event, and what precisely are the stimuli that
      modulate the activity of the cardiac renin-angiotensin system, are questions that
      are still poorly understood, but being actively researched.

PMID- 8281961
TI  - Left ventricular hypertrophy in asymptomatic essential hypertension: its
      relationship with aldosterone and the increase in sodium-proton exchanger
      activity.
AB  - In order to analyse the hormonal and erythrocyte ion transport systems in
      relation to left ventricular hypertrophy (LV) in essential hypertension, a
      prospective study of 50 consecutive hypertensive patients under 55 years of age
      and without prior antihypertensive therapy was performed. Twenty-seven normal
      subjects with no family history of hypertension served as controls. LV
      hypertrophy, as assessed by echocardiography, was present in 64% of the
      hypertensive patients. This showed an increase (P < 0.001) in intra-erythrocyte
      Na+ concentration (8.1 +/- 1.2 vs 6.9 +/- 1 mmol.l-1.cells-1) and Na+:H+ exchange
      activity (8.8 +/- 4 vs 5.5 +/- 1.3 mmol.[l.cells.h-1]). There was a significant
      association between plasma aldosterone levels (19.1 +/- 12 ng.dl-1) with intra
      erythrocyte Na+ content (r = 0.370, P < 0.05) and Na+:H+ exchange activity (r =
      0.385, P < 0.01) as well as with echocardiographic LV mass index (138 +/- 40 g.m
      2, r = 0.393, P < 0.01). The results are consistent with the concept that
      increased entry of Na+ into cells via Na+:H+ exchange could be a determining
      factor in left ventricular hypertrophy, which might be influenced by aldosterone.

PMID- 8281963
TI  - Hypothetical pathways of cardiac myocyte hypertrophy: response to myocardial
      injury.
AB  - The heart is made up of many different cell types, including myocytes,
      fibroblasts and vascular cells. The cardiac myocyte, although not likely to
      divide, may respond to gross organ injury by a process of growth or hypertrophy.
      Cellular hypertrophy, though a normal biological adaptation, has the potential to
      contribute to the change in the shape and the size of the heart, such as occurs
      in chronic heart failure. We are now just beginning to understand the signals and
      early pathways involved in the cardiac myocyte growth response, some of which are
      reviewed herein.

PMID- 8281964
TI  - Renin-angiotensin system and myocardial fibrosis in hypertension: regulation of
      the myocardial collagen matrix.
AB  - The cardiac interstitium is composed of non-myocyte cells embedded in a highly
      organized extracellular matrix containing a three-dimensional collagen network
      which serves to maintain the architecture of the myocardium and determines
      myocardial stiffness. In hypertensive heart disease, a heterogeneity in
      myocardial structure, created by the altered behaviour of cardiac fibroblasts
      responsible for collagen synthesis and degradation, can explain the appearance of
      diastolic and ultimately systolic dysfunction of the left ventricle. In vivo,
      circulating and myocardial renin-angiotensin systems (RAS) were found to be
      involved in the regulation of the structural remodelling of the cardiac
      interstitium. In vitro, in cultured adult rat cardiac fibroblasts, angiotensin II
      was shown to stimulate collagen synthesis and to inhibit collagenase activity,
      which is the key enzyme for collagen degradation. In the SHR-model of primary
      hypertension, left ventricular hypertrophy could be regressed and abnormal
      myocardial diastolic stiffness, due to interstitial fibrosis, could be restored
      to normal by inhibition of the myocardial RAS. These antifibrotic or
      cardioreparative effects of ACE inhibition that occurred irrespective of blood
      pressure normalization may be valuable in reversing left ventricular diastolic
      dysfunction in hypertensive heart disease.

PMID- 8281965
TI  - Ventricular arrhythmias in left ventricular hypertrophy and heart failure.
AB  - The significance of ventricular hypertrophy in the genesis of ventricular
      tachyarrhythmias cannot be over-emphasized. Left ventricular hypertrophy, as a
      consequence of arterial hypertension, influences the three factors involved in
      the prognosis and we express these as a triangle of risk: electrical instability,
      left ventricular dysfunction and ischaemia.

PMID- 8281966
TI  - Mechanisms of ventricular arrhythmias in the presence of pathological
      hypertrophy.
AB  - Ventricular extrasystoles and the complex forms of non-malignant ventricular
      arrhythmias clearly increase in the presence of left ventricular hypertrophy.
      Left ventricular hypertrophy constitutes a clear sudden death risk factor. The
      connection between possible malignant arrhythmias, which have also been reported
      in LVH patients, and an increased incidence of sudden death has not been
      established. Hypertension, electrical changes in the hypertrophic myocyte, the
      growth of the collagen matrix and ischaemia (even in the absence of macro
      angiographic injuries) are factors present in this group of patients that
      contribute to the appearance of arrhythmias. The arrhythmogenic substrate of LVH
      has to do with reentry mechanisms due to fibrillar stretching and anisotropy, as
      well as with self-sustaining activity triggered by after-potentials that depend
      on activation of slow calcium channels.

PMID- 8281967
TI  - Treatment of ventricular arrhythmias in patients with hypertrophic
      cardiomyopathy.
AB  - In patients with hypertrophic cardiomyopathy, asymptomatic episodes of non
      sustained ventricular tachycardia are frequent and of prognostic significance for
      sudden cardiac death in adults, particularly in those whose consciousness is
      impaired. Low-dose amiodarone, found to be beneficial in mildly symptomatic non
      sustained ventricular tachycardia, but detrimental in a subgroup with prominent
      non-arrhythmic symptoms, could be an alternative to an electrophysiological
      approach in patients with syncope but preserved functional capacity. In cardiac
      arrest survivors, an electrophysiological approach seems preferable to empiric
      amiodarone, together with implantation of a defibrillator, at least in those in
      whom inducible arrhythmias cannot be suppressed.

PMID- 8281968
TI  - Prognostic significance of ventricular arrhythmias in the presence of
      pathological left ventricular hypertrophy.
AB  - It is well known that pathological left ventricular hypertrophy, either primary
      or secondary to cardiac overload, is associated with a high incidence of
      ventricular arrhythmias and sudden death, and that asymptomatic ventricular
      arrhythmias seem to be related to a high incidence of sudden death in patients
      with hypertrophic cardiomyopathy and ischaemic heart disease. However, this
      association has not been prospectively evaluated in patients with hypertensive
      LVH, where other factors, such as myocardial ischaemia, can play an important
      role. More studies are needed in this respect before establishing therapeutic
      implications.

PMID- 8281969
TI  - Origin and mechanisms of heart failure in hypertensive patients: left ventricular
      remodelling in hypertensive heart disease.
AB  - This review-editorial proposes a biological explanation for most of the
      physiological characteristics of the hypertrophied chronically overloaded heart.
      Various growth signals, including mechanical, hormonal and paracrine factors,
      appear now to be involved in the induction of myocyte hypertrophy and/or
      phenotypic modifications. A majority of the modifications in passive myocardial
      compliance are due to an enhanced collagen density, and the diminution of the
      atrial contribution to ventricular filling is certainly a consequence of an
      isomyosin change in this particular tissue. The systolic dysfunction reflects, in
      fact, one of the most essential parts of the adaptational process, the slowing of
      Vmax. In humans, this diminution is a consequence of a rather complex change in
      the expression of various genes coding for proteins responsible for myoplasmic
      calcium transient. Arrhythmogenicity, a well-known detrimental property of the
      hypertrophied heart, reflects the fragility of calcium homeostasis in this type
      of cell, and this fragility is likely to be a direct consequence of membrane
      protein rearrangement.

PMID- 8281970
TI  - Origin and evaluation of depressed inotropism in hypertensive cardiomyopathy.
AB  - Left ventricular pressure overload results in the development of left ventricular
      hypertrophy (LVH) which is considered an adaptive mechanism of the heart to
      normalize systolic wall-stress. Impairment of both contractility and relaxation
      occurs, implying that the hypertrophied myocardium is very sensitive to
      ischaemia, alterations in coronary haemodynamics and to mechanisms incompletely
      understood. Experimental data from papillary muscles and isolated coronary
      perfused hearts (renovascular hypertensive rats) demonstrated respectively: a
      decrease in velocity of shortening, an increase in isometric timing parameters,
      and an increase in developed pressure. In contrast, the first derivative of left
      ventricular pressure, normalized to developed pressure, was decreased for large
      balloon volumes, suggesting an impairment of systolic function at major loading
      in LVH. In humans, left ventricular systolic dysfunction occurs later (congestive
      heart failure) when ejection fraction is impaired. Increases in total minimal
      vascular coronary resistances observed both in humans and in animals could be
      related to structural and functional alterations in coronary microvessels.
      Studies of LVH regression under treatment with angiotensin-converting enzyme
      inhibitors, calcium-channel blockers and beta-receptor blockers have confirmed
      that only drugs that block the renin-angiotensin system or the sympathetic
      nervous system are effective in maximizing the reversal of LVH.

PMID- 8281971
TI  - Doppler echocardiographic evaluation of diastolic function in hypertensive
      cardiomyopathies.
AB  - In hypertensive cardiomyopathies, diastolic function is abnormal due to impaired
      relaxation associated with left ventricular hypertrophy, and a variable degree of
      reduction in left ventricular compliance may also be present. Abnormal relaxation
      can be indicated from prolonged isovolumic relaxation time and reduced early
      diastolic mitral inflow velocity, as well as from a reduced rate of posterior
      wall thinning and the neg dp/dt estimated from a continuous wave recording of
      mitral regurgitation. Reduction in left ventricular compliance can be assessed
      from shortening of the mitral A-wave, and from increased flow reversal in the
      pulmonary veins at atrial contraction. Non-invasive assessment of LV diastolic
      function is therefore possible by recording mitral and pulmonary venous flow
      velocities and posterior LV wall motion.

PMID- 8281972
TI  - Classification of hypertensive cardiomyopathy.
AB  - A clinical pathophysiological classification of hypertensive cardiomyopathy has
      been established on the basis of the degree to which the heart is affected by
      chronic, systemic arterial hypertension: Degree I: Asymptomatic patients without
      left ventricular hypertrophy but with left ventricular diastolic dysfunction
      according to Doppler mitral inversion relation (E/A < 0.9) or to gamma
      scintigraphy (peak filling rate reduction < or = 2.7 EDC.s-1. These patients are
      classified as Group 1. Degree II: Asymptomatic or mildly symptomatic patients
      (New York Heart Association class I) with echocardiographic left ventricular
      hypertrophy; classified as Group IIA or IIB according to whether weight-adjusted
      maximal oxygen uptake is normal or below normal, respectively. Degree III: The
      basic characteristic is the presence of congestive heart failure with normal
      ejection fraction (EF > or = 50%). Two subsets can be distinguished on the basis
      of degree of hypertrophy: Group IIIA, with a mass/volume index > 1.8, and IIIB
      with a mass/volume index < 1.8. The differences between the two are as follows:
      patients classified as IIIA had a lower rate of regional ischaemia, a higher
      ejection fraction, a more frequently audible fourth sound, rarely a third sound
      and a cardiothoracic ratio < 0.5; IIIB patients had a higher prevalence of
      regional ischaemia (thallium-positive), a frequently audible third sound and a
      cardiothoracic ratio > 0.5. Degree IV: This category is characterized by the
      presence of depressed contractility, which could cause heart failure, by an
      ejection fraction < 50% and an increase in ventricular volumes. Echocardiography
      shows increased distance between mitral point E and the septum.

PMID- 8281973
TI  - Shiftwork and the older worker.
AB  - The number of workers employed on shiftwork is large, and it appears to be
      increasing. The impact of shiftwork on the occupational safety and health of
      workers is complex and involves both biological and behavioral variables. Current
      conceptual models propose that the impact of shiftwork, where night work is
      involved, increases with exposure. At some point the worker is said to reach a
      tolerance limit beyond which shiftwork is no longer safe. Sleep variables have
      proven to be sensitive markers for the effects of night shiftwork. Data from U.S.
      workers show a statistically significant interaction among age, gender, and shift
      for the workday sleep length of workers on permanent day, afternoon/evening, and
      night shifts. Sleep length declines with age for both male and female night
      workers, as well as for male workers on afternoon/evening shifts. In addition,
      female night workers in the 18-49 age range sleep significantly less than same
      age male night workers. Nap behavior also varies with shift, but age and gender
      effects do not appear to account for the variance. The results support the
      assumption that most night shiftworkers are at risk even though they often give
      the appearance of being able to tolerate nocturnal work hours. However, it is not
      yet clear how age and gender are related to the social, circadian, and
      environmental factors that influence the sleep length of shiftworkers.

PMID- 8281974
TI  - Effects of organization and working memory on age differences in memory for scene
      information.
AB  - We examined the effects of organization and working memory on young and older
      adults' scene memory. Subjects discriminated transformed pictures from unchanged
      study items in organized or unorganized scenes. Memory was tested independently
      for two types of scene transformations: (a) relocations (two objects rearranged
      and one moved) and (b) substitutions (one object replaced by another).
      Organization had similar effects on young and older adults, improving memory for
      relocations but not substitutions. Working memory significantly predicted scene
      memory, except for relocations in organized scenes, and partially mediated the
      observed age effects. The results are discussed in relation to the resource and
      environmental support views of cognitive aging.

PMID- 8281975
TI  - Adult age differences in spatial memory: effects of structural context and
      practice.
AB  - We examined the effect of structural context on memory for spatial location in
      young and elderly women in two studies. Subjects studied and later reconstructed
      an array of visually identical objects that were positioned in a three
      dimensional Plexiglas matrix. For half the subjects, small household objects were
      interspersed in the array to serve as spatial landmark cues during encoding and
      replacement. All subjects received two study and replacement trials. The results
      indicated that (a) older women remembered fewer locations than younger women but
      benefited more from landmark cues to location, (b) performance improved on the
      second replacement trial for the young but not for the older women, and (c) both
      age groups appeared to use similar processing strategies that were based on the
      vertical dimension of space. These results suggest that structural context
      enhances older adults' retention of three-dimensional spatial information. The
      implications of these data for the conceptual distinction between structural and
      organizational aspects of spatial context are discussed.

PMID- 8281976
TI  - Adult age differences in temporal memory for cyclic actions.
AB  - Adult age differences in temporal memory for bipolar or cyclic actions were
      investigated in three experiments. Cyclic actions are ones that have opposite
      poles in regard to their effect on an object (e.g., opening and closing a purse).
      For such actions, the critical memory function is to remember which pole occurred
      last. Temporal memory was tested by having subjects judge which component of a
      series of bipolar actions had been performed more recently (e.g., opening or
      closing a purse). Recency judgments were found to be as accurate under incidental
      memory conditions as they were under intentional memory conditions for both young
      and elderly adults. The accuracy of recency judgments was less for bipolar
      actions performed in three cycles than for bipolar actions performed in one cycle
      for both young and elderly adults. Adult age differences in the accuracy of
      recency judgments were found to be negligible.

PMID- 8281977
TI  - Are age-related behavioral disorders improved by folate administration?
AB  - In this brief review of the possible link between age-related behavioral
      disorders and brain folate levels, preliminary data on humans and animals are
      presented. These data indicate that folate administration may improve some age
      related behavioral dysfunctions. In aged humans and rats, there is a defect in
      the absorption of dietary folate, leading perhaps to a decrease in brain folate
      levels. If so, folate therapy may replenish brain stores of folates and may
      reverse some age-related behavioral deficits. Some questions concerning the
      possible relationship among mood status, intellectual functions, and folate
      levels in aging are discussed.

PMID- 8281978
TI  - 11 beta-hydroxysteroid dehydrogenase isoforms and their implications for blood
      pressure regulation.
AB  - 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyzes the reversible
      conversion of physiological glucocorticoids (cortisol, corticosterone) to
      inactive products. The enzyme thus protects non-selective renal mineralocorticoid
      receptors from circulating glucocorticoids (ensuring aldosterone-selectivity in
      vivo), excludes maternal glucocorticoids from the foetal circulation and
      modulates glucocorticoid access to glucocorticoid receptors in other tissues. 11
      beta-HSD has been purified from rat liver, antisera raised, a cDNA isolated and
      its human homologue cloned. However, it is difficult to reconcile all of the
      actions of 11 beta-HSD with a single enzyme. Here data are reviewed that
      demonstrate not only molecular heterogeneity of the 'liver-type' 11 beta-HSD, but
      also the existence of a novel high affinity isoform in the placenta and perhaps
      distal nephron. These data are discussed in the light of their potential
      physiological and pathological importance, with particular reference to the
      pathogenesis of hypertension.

PMID- 8281979
TI  - No evidence for feedback inhibition of hepatic apolipoprotein B (apo B)
      production after extracorporeal low density lipoprotein precipitation as
      determined by [1-13C]leucine infusion in normal volunteers.
AB  - To determine the impact of an acute reduction of the circulating mass of
      apolipoprotein B (apo B) on apo B metabolism we studied six healthy male
      volunteers before (day 0), 1 day after (day 2), and 7 days after (day 8) an LDL
      apheresis treatment which reduced apo B mass by 59%. Appearance of newly
      synthesized apo B in plasma VLDL and LDL was studied using a primed-constant
      infusion of [1-13C]-leucine. VLDL apo B pool size and fractional VLDL apo B
      production rate calculated using a one-compartment model were similar on all 3
      study days. Absolute VLDL apo B production was not statistically different
      throughout the study (19.7 +/- 12.3, 19.5 +/- 7.5, 29.1 +/- 17.7 mg kg-1 day-1).
      LDL apo B fractional production rate was increased on day 2 (0.38 +/- 0.17, 0.68
      +/- 0.08, 0.37 +/- 0.06 pools day-1 on days 0, 2, and 8; P < 0.01). Absolute LDL
      apo B production, however, remained constant throughout the study (10.8 +/- 3.3,
      11.0 +/- 1.9, 10.8 +/- 3.1 mg kg-1 day-1). We conclude that in healthy male
      volunteers acute reduction of the circulating apo B mass by LDL apheresis does
      not affect apo B metabolism significantly.

PMID- 8281980
TI  - Angiotensin converting enzyme activity in the serum, lung and kidney of diabetic
      rats.
AB  - Diabetes Mellitus in its early stages, is associated with kidney enlargement and
      increased glomerular filtration rate in humans and in rats. The present study was
      designed to clarify the direct effect of diabetes on serum and tissue angiotensin
      converting enzyme (ACE) activity in streptozotocin-induced diabetic rats. Serum
      ACE activity, as determined using a radiometric assay, was significantly
      increased in the diabetic rats (n = 15) 14 days after induction of diabetes (670
      +/- 31 vs. 506 +/- 14 nmol ml-1 min-1). Lung ACE activity, but not renal, was
      significantly elevated at 7 and 14 days by 29 and 46%, respectively. Plasma renin
      activity in the diabetic rats was decreased at 7 and 14 days by 41 and 78%,
      respectively. Incubations of lung slices in the presence of glucose at different
      concentrations did not affect in-vitro release of the enzyme. Administration of
      insulin (8 units kg-1) to diabetic rats (n = 6) on the 4th day for 11 days
      reduced ACE activity to values below control. Thus, serum and lung ACE activity
      is increased in the diabetic rat and reduced upon insulin treatment.

PMID- 8281981
TI  - Smoking and plasma lipoproteins in man: effects on low density lipoprotein
      cholesterol levels and high density lipoprotein subfraction distribution.
AB  - In a survey of a healthy population (n = 197), LDL cholesterol, plasma
      triglycerides and VLDL triglycerides were found to be substantially increased and
      plasma HDL cholesterol decreased in smokers. The lipid-associated atherogenic
      risk in smokers as assessed by the LDL/HDL ratio was significantly higher [2.89
      (SD 1.18, n = 63)] than in non-smokers [2.38 (SD 0.98, n = 86) P < 0.01]. The
      lower HDL level found in smokers was explained by a lower HDL-2 subfraction as
      determined by analytical ultracentrifugation. HDL 2b, 2a and 3a, measured by
      gradient gel electrophoresis, were all lower in the smokers but this was only
      significant for HDL 2a. Smoking had no effect on Lp(a) levels. HDL cholesterol
      and HDL-2 were strongly negatively correlated whereas LDL cholesterol and LDL/HDL
      ratio were strongly positively correlated with the plasma triglyceride
      concentration. There was a small but significant reduction in plasma CETP
      activity [non-smokers 49% t/microliter (SD 17, n = 90), smokers 43% t/microliter
      (SD 17, n = 66) P < 0.05] but CETP activity was not correlated with any measure
      of HDL in this population. Smoking was found to be an important independent
      contributor to the variation in plasma triglyceride, HDL, HDL-2 and LDL/HDL
      ratio. After correcting for sex, age, BMI, alcohol consumption, oral
      contraceptive use and plasma triglycerides smoking was still found to be
      significantly associated with HDL and the LDL/HDL ratio. Upon adjustment for
      covariant factors the mean differences between smokers and non-smokers for HDL
      cholesterol, HDL-2 and LDL/HDL were 0.15 mM, 16 mg dl-1 and 0.39 respectively.
      There appeared to be important sex differences in the influence of smoking on
      plasma lipoproteins. In women the main impact of smoking was on triglyceride
      levels and they in turn affected LDL and HDL. In contrast, in men, smoking had
      little impact on triglycerides and affected HDL more directly. We conclude that
      smoking cigarettes has an important effect on plasma lipoprotein metabolism
      through multiple mechanisms.

PMID- 8281982
TI  - Effects of diet and the cholecystokinin antagonist; devazepide (L364,718) on CCK
      mRNA, and tissue and plasma CCK concentrations.
AB  - The mechanisms by which raw soya diets and CCK-receptor antagonists increase
      postprandial plasma CCK concentrations are not fully understood. Therefore we
      examined the effects of different diets including raw soya, and the effect of the
      potent CCK antagonist devazepide in the fed and fasted state on CCK
      concentrations in plasma and in the duodenal mucosa and on the duodenal CCK:beta
      tubulin mRNA ratio in rats. Diets which stimulated high plasma CCK levels, such
      as raw soya, also gave the highest CCK tissue and mRNA concentrations with a
      close correlation between plasma and tissue CCK concentrations within each group
      (r = 0.94, P = 0.018) and between tissue CCK concentrations and CCK:beta-tubulin
      mRNA ratios (r = 0.91, P = 0.030). Animals fed ad libitum and treated with
      devazepide (1 mg kg-1) had higher CCK:beta-tubulin mRNA ratios, tissue CCK
      concentrations and plasma CCK concentrations than animals injected with vehicle.
      Fasted animals treated with devazepide for 28 h also had higher CCK mRNA:beta
      tubulin mRNA ratios (1.86 +/- 0.43 vs. 0.85 +/- 0.15, P < 0.05), and higher
      tissue CCK concentrations (0.99 +/- 0.09 vs. 0.69 +/- 0.04, P < 0.01). However,
      despite these intracellular changes devazepide did not elevate plasma CCK
      concentrations in the fasted state. Therefore, devazepide increases tissue
      concentrations of CCK but requires an additional dietary stimulus to raise plasma
      concentrations. These findings indicate that devazepide produces a dissociation
      between synthesis and release of CCK in fasted animals.

PMID- 8281983
TI  - Dietary saturated fatty acids increase cholesterol synthesis and fecal steroid
      excretion in healthy men and women.
AB  - In a strictly controlled 6-week trial with 47 healthy volunteers we have
      determined the effect of replacement of polyunsaturated by saturated fatty acids
      on the fecal steroid excretion and on the rate of whole body cholesterol
      synthesis, as measured both by the sterol balance method and by the concentration
      of the cholesterol precursor lathosterol in serum. Subjects were fed mixed
      natural diets, of which the total fat content was kept constant at 45% energy.
      Consumption of polyunsaturated fatty acids, mainly linoleic acid, was 21% energy
      for the first 3-week period (P:S ratio 1.9), and 5% of energy (P:S ratio 0.2) for
      the next 3-week period, or vice versa. Cholesterol intake as determined by
      analysis of duplicate diets was 41 mg MJ-1 (about 500 mg day-1) during both
      periods. Feces were collected for 5 days at the end of both periods. The steroid
      composition of the feces was not affected by the change of diets. The fecal
      excretion of neutral steroids was significantly higher on the low P:S high
      saturated-fat (2.25 +/- 0.68 mmol day-1) than on the high P:S high-linoleic-acid
      diet (2.00 +/- 0.69 mmol day-1; P < 0.01). The excretion of bile acids was
      similar (0.77 +/- 0.40 and 0.79 +/- 0.41 mmol day-1, respectively). The
      cholesterol balance and the rate of cholesterol synthesis were higher during the
      low P:S (1.86 +/- 0.83 mmol day-1) than during the high P:S period (1.55 +/- 0.85
      mmol day-1; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8281984
TI  - Liposomal dexamethasone effectiveness in the treatment of hypersensitivity
      pneumonitis in mice.
AB  - The effects of daily intranasal instillation of liposomal dexamethasone and free
      dexamethasone phosphate were compared in a murine model of hypersensitivity
      pneumonitis induced by Saccharopolyspora rectivirgula (formally known as
      Micropolyspora faeni). After 3 weeks of antigen and liposome instillations, lung
      response was evaluated by bronchoalveolar lavage cell counts, lung index and
      histopathology. Systemic absorption was evaluated by measuring plasma
      adrenocorticotropic hormone (ACTH) level. Free dexamethasone phosphate induced a
      dose-dependent response with the maximal effect reached at 1 mg kg-1. At 0.1 mg
      kg-1, liposomal dexamethasone had a greater effect than free dexamethasone
      phosphate on bronchoalveolar cells ml-1: 3.01 x 10(5) +/- 0.35 x 10(5) compared
      to 4.70 x 10(5) +/- 0.34 x 10(5), and lung index: 1.22 +/- 0.10 compared to 1.86
      +/- 0.07. Effect on histopathology was similar. Plasma ACTH levels (pg ml-1)
      were: 75.1 +/- 14.0 for animals receiving antigen and free dexamethasone
      phosphate (0.2 mg kg-1), and 149.7 +/- 12.0 for animals receiving antigen and
      liposomal dexamethasone (0.2 mg kg-1). In conclusion, liposome-incorporated
      dexamethasone is efficient in the treatment of experimental hypersensitivity
      pneumonitis and, contrarily to free dexamethasone phosphate, does not inhibit
      ACTH secretion.

PMID- 8281985
TI  - Peripheral macro- and microcirculation in short-term insulin-dependent diabetes
      mellitus: the role of prostaglandins in early haemodynamic changes.
AB  - To determine whether vasodilator prostaglandins are involved in the peripheral
      hyperperfusion observed in patients with short-term insulin-dependent diabetes
      mellitus (IDDM), forearm and skin blood flow were studied before and after
      cyclooxygenase inhibition. Skin nutritive (CBV: capillary blood-cell velocity)
      and thermoregulatory (LDF: laser-Doppler fluxmetry), and forearm (muscle) blood
      flow (FBF) were measured before and after 500 mg acetylsalicylic acid (ASA)
      infused intravenously in 14 short-term IDDM patients and 22 healthy control
      subjects. In the IDDM patients, baseline LDF (median: 27 (19-35); interquartile
      range) vs. 17 (15-23) pu) and FBF (3.4 (2.5-4.1) vs. 2.6 (2.2-2.9) ml 100 ml-1
      min-1) were increased, while CBV (0.70 (0.40-1.33) vs. 0.69 (0.41-0.96) mm s-1)
      was unchanged compared to healthy controls. ASA infusion had similar effects on
      baseline CBV, LDF, and FBF in patients and controls. In eight of the control
      subjects the role of prostaglandins in the regulation of basal peripheral blood
      flow was studied before and after ASA and placebo infusion. The changes in
      baseline CBV, LDF, and FBF were similar after ASA and placebo infusion in healthy
      controls. In conclusion, in short-term IDDM patients, increased skin
      thermoregulatory and forearm (muscle) blood flow are probably not related to
      vasodilator prostaglandins. Furthermore, prostaglandins are not likely to be
      involved in regulating basal peripheral blood flow in healthy man.

PMID- 8281986
TI  - [3H]7-OH-DPAT labels both dopamine D3 receptors and sigma sites in the bovine
      caudate nucleus.
AB  - The binding of [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) to
      membranes of the bovine caudate nucleus was characterized and shown to be
      heterogenous. While [3H]7-OH-DPAT labels the dopamine D3 receptor in this tissue
      (Ki = 4.8 nM), as shown by its sensitivity to dopamine and (-)-quinpirole, it
      also binds with high affinity (Ki = 48 nM) to sigma recognition sites. The
      present results demonstrate that [3H]7-OH-DPAT is a useful radioligand to label
      native D3 receptors in the bovine caudate, although care must be taken to assure
      its selectivity.

PMID- 8281987
TI  - Peripheral mechanisms of opioid antinociception in inflammation: involvement of
      cytokines.
AB  - It has been shown previously that opioids induce antinociceptive effects at
      peripheral sites in the presence of inflammatory processes. Besides being
      elicited by local injection of opioids, such effects can also be obtained by
      activation of intrinsic opioid mechanisms, e.g. following stress. In the present
      study the possible role of cytokines in this mechanism was investigated.
      Unilateral inflammation of the hindpaw of rats was induced by local injection of
      Freund's complete adjuvant. Intraplantar injection of tumor necrosis factor alpha
      (TNF alpha) or interleukin-6 induced a dose-dependent increase in the threshold
      in the paw pressure test in the inflamed but not in the non-inflamed paw. This
      increase was prevented by local injection of naloxone and the mu-opioid receptor
      specific antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) as well as by
      3-E7, an universal opioid peptide antibody. In rats pretreated with cyclosporin A
      to suppress the immune system, the antinociceptive effect of TNF alpha was
      completely inhibited. In concert with previous studies these data indicate that
      the tested cytokines release opioid peptides (e.g. beta-endorphin and/or
      enkephalins) from immune cells of the inflamed tissue which act on opioid
      receptors present on sensory nerve terminals, resulting in antinociception.

PMID- 8281988
TI  - Effects of one-hour and one-week treatment with ramipril on plasma and renal
      brush border angiotensin converting enzyme in the rat.
AB  - Prolonged treatment with an angiotensin converting enzyme inhibitor produces an
      induction of plasma angiotensin converting enzyme. Induction of angiotensin
      converting enzyme in tissues during prolonged treatment with an angiotensin
      converting enzyme inhibitor is less well documented. We compared the effects of 1
      h and 1 week treatment with ramipril (0.1, 0.3, 1 mg/kg) on angiotensin
      converting enzyme activity in the plasma, renal cortex and renal brush border
      membrane of Wistar rats. As an increase in activity could be masked by the
      inhibition due to the presence of ramiprilat which is the active form of
      ramipril, we eliminated the ramiprilat present in renal cortex homogenates with
      EGTA during brush border preparation. The 1-h treatment with ramipril induced a
      dose-dependent inhibition of plasma and renal cortex angiotensin converting
      enzyme activity. The 1-week treatment with ramipril produced an increase in
      plasma angiotensin converting enzyme activity, whereas renal cortex angiotensin
      converting enzyme activity decreased. The decrease in angiotensin converting
      enzyme activity persisted in the brush border membrane after elimination of
      residual ramiprilat with EGTA. Our results show that prolonged ramipril treatment
      produces opposite responses in plasma and renal cortex angiotensin converting
      enzyme activity, suggesting that plasma and epithelial angiotensin converting
      enzymes are subject to specific local regulatory factors.

PMID- 8281989
TI  - Effect of ramipril on alpha-adrenoceptor-mediated oscillatory contractions in
      tail artery of hypertensive rats.
AB  - Recent studies indicate that norepinephrine-induced contractile oscillations in
      the tail artery from stroke-prone spontaneously hypertensive rats (SHRSP) may be
      a vascular phenomenon independent of blood pressure level. The objectives of this
      study were: (1) to characterize pharmacologically the alpha-adrenoceptor
      mediating norepinephrine-induced oscillations in tail artery; and (2) to
      investigate the relationship between blood pressure level, altered by treatments
      with hydralazine/hydrochlorothiazide or the angiotensin converting enzyme
      inhibitor ramipril, and the observation of norepinephrine-induced oscillations in
      tail artery. The alpha 2-adrenoceptor agonists clonidine and guanabenz potently
      stimulated oscillatory contractions in the tail artery while the alpha 1
      adrenoceptor agonists phenylephrine and methoxamine were considerably less
      potent. Yohimbine, an alpha 2-adrenoceptor antagonist, but not the alpha 1
      adrenoceptor antagonist prazosin demonstrated high affinity for the receptor
      mediating norepinephrine-induced oscillatory contractions. These results support
      the hypothesis that norepinephrine-induced oscillatory contractions in the tail
      artery from SHRSP occur primarily through stimulation of alpha 2-adrenoceptors.
      Ramipril lowered blood pressure in SHRSP after 4 weeks of treatment during 6-10
      weeks of life but did not alter the ability of the alpha 2-adrenoceptor agonist
      clonidine (10(-5) M) to induce contractile oscillations in tail arteries from
      SHRSP, indicating these oscillations are not a secondary effect of high blood
      pressure. These studies suggest that norepinephrine-induced oscillations in tail
      artery from SHRSP may be a vascular trait separate and distinct from blood
      pressure level and angiotensin II expression early in life.

PMID- 8281990
TI  - Relaxation by calcitonin gene-related peptide may involve activation of K+
      channels in the human uterine artery.
AB  - The vasodilatory role of calcitonin gene-related peptide in activating K+
      channels was examined in isolated, suffused human uterine arteries. Calcitonin
      gene-related peptide produced a concentration-dependent relaxation of
      norepinephrine (1 microM)-induced contractions. Calcitonin gene-related peptide
      was antagonized by glybenclamide (1-100 microM), an inhibitor of ATP-sensitive K+
      channels, but not by tetraethylammonium (1 mM), an inhibitor of calcium(2+)
      activated K+ channels. Glybenclamide (10 microM) produced a 6.7 fold and an 11
      fold shift to the right of calcitonin gene-related peptide (0.1 to 100 nM) in
      uterine arteries from pregnant patients (n = 3) and nonpregnant patients (n = 6),
      respectively. Calcitonin gene-related peptide (10 nM) less effectively (P < 0.05)
      relaxed contractions produced by KCl (50 mM) (29.4 +/- 1.6%) than by
      norepinephrine and glybenclamide (10 microM) did not reverse this relaxation
      (22.2 +/- 6.8%, n = 4 nonpregnant patients). Pinacidil (1 microM), an ATP
      sensitive K+ channel opener, relaxed norepinephrine-induced contractions of
      uterine arteries. Glybenclamide (10 microM) also antagonized pinacidil. These
      results suggest that calcitonin gene-related peptide relaxes norepinephrine
      contracted human uterine arteries, at least in part, by activation of a K+
      channel, perhaps of the ATP-sensitive type.

PMID- 8281991
TI  - Effects of haemoglobin and N-nitro-L-arginine on constrictor and dilator
      responses of aortic rings from streptozotocin diabetic rats.
AB  - This study investigated the effects of N-nitro-L-arginine and haemoglobin on
      responses of aortic rings (10 g resting tension) from 2-week streptozotocin
      diabetic and control rats. N-Nitro-L-arginine (0.1 mM) or haemoglobin (10 microM)
      potentiated constrictor responses of aortae from both groups of rats to 5
      hydroxytryptamine (5-HT) or noradrenaline. They also overcame the tachyphylaxis
      which occurred on the second exposure to 5-HT. Following constriction of aortae
      with 5-HT or noradrenaline, acetylcholine produced concentration-dependent
      relaxation. At concentrations of acetylcholine of 0.1 microM to 0.1 mM for 5-HT
      constricted rings, and 0.1 microM for noradrenaline-constricted rings, the
      specific component of relaxation attributable to acetylcholine was significantly
      less for aortae from diabetic rats than for those from controls. For aortae from
      both groups, N-nitro-L-arginine (or haemoglobin) inhibited relaxation in the
      presence of acetylcholine (noradrenaline or 5-HT-constricted rings), and N-nitro
      L-arginine (or N-nitro-L-arginine with haemoglobin) partially inhibited
      spontaneous relaxation of 5-HT-constricted rings. These results suggest that NO
      may play a role in tachyphylaxis to 5-HT, and that acetylcholine-induced output
      of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) (or responsiveness
      to EDRF/NO) may be reduced in noradrenaline- and 5-HT-constricted aortic rings
      from 2-week diabetic rats.

PMID- 8281992
TI  - Effects of chronic discontinuous and continuous treatment of rats with a dopamine
      D1 receptor antagonist (NNC-756).
AB  - Rats were treated intermittently or continuously with the dopamine D1 receptor
      antagonist NNC-756 for 15 weeks. Two weeks after withdrawal they were challenged
      with the dopamine D1 receptor agonist SK&F 38393, either alone or after
      pretreatment with NNC-756. Neither treatment regimen resulted in irreversible
      increases in oral activities when treated rats were compared with controls;
      however, transient elevations were observed in the beginning of treatment in the
      continuously treated group and in the withdrawal phase in the discontinuously
      treated group. Furthermore, discontinuous treatment resulted in within-group
      elevations in vacuous chewing movements and tongue protrusions after withdrawal.
      Dopamine D1 receptor supersensitivity was not observed after challenge with the
      dopamine D1 receptor agonist. NNC-756 efficiently blocked the behavioural
      response to stimulation with SK&F 38393. Both treatment regimens resulted in the
      development of rigidity and catalepsy. The present study suggests that treatment
      with selective dopamine D1 receptor antagonists is less likely to cause
      irreversible oral dyskinesia than is treatment with classical neuroleptic drugs.

PMID- 8281993
TI  - Ex vivo effect of insulin on normal and diabetic rat hearts hypoperfused with
      norepinephrine.
AB  - The effect of ex vivo insulin on contractile and energy metabolism dysfunctions
      was examined during hypoperfusion (0.6 ml/min per g heart weight) with 10(-6) M
      norepinephrine in isolated non-diabetic and streptozotocin-diabetic rats hearts.
      Insulin (2 mU/min per g heart weight) was infused for 15 min before as well as
      during 60-min hypoperfusion. Insulin significantly reduced the elevated diastolic
      tension in diabetic hearts (from 3.8 to 0.7 delta g), but not in non-diabetic
      hearts (from 1.4 to 1.2 delta g). Insulin partly improved the ATP decrease in the
      subendocardium of the left ventricle of the diabetic hearts (from 3.5 to 10.2
      mumol/g dry weight) but did not affect non-diabetic hearts (from 6.9 to 6.8
      mumol/g dry weight). Insulin also partly improved the creatine phosphate decrease
      and the inorganic phosphate increase in diabetic hearts only. Lactate
      accumulation was greater in non-diabetic than in diabetic hearts, even in the
      presence of insulin (77 vs. 45 mumol/g dry weight). The results indicate that
      acute intracoronary application of insulin in diabetic hearts improves
      hypoperfusion with norepinephrine injury to a level above that of non-diabetic
      hearts, but does not improve a less severe injury in non-diabetic hearts.

PMID- 8281994
TI  - Effects of clonidine on desipramine- and desmethylclomipramine-induced 3-methoxy
      4-hydroxyphenylglycol levels in rat brain.
AB  - Rats received repeated i.p. administrations of desipramine (20 mg/kg) or
      desmethylclomipramine (10 mg/kg). The steady state concentration of each drug in
      the brain was attained a few days after the start of the treatment. The
      treatments with desipramine and desmethylclomipramine for more than 10 and 2
      days, respectively, induced significant elevation of 3-methoxy-4
      hydroxyphenylglycol (MHPG) level in the brain. After repeated administration of
      each drug, rats were given a single i.p. injection of clonidine (50
      micrograms/kg). This treatment decreased the elevated MHPG level in the brain of
      desmethylclomipramine-treated rats, whereas it had no effect on the increased
      MHPG level in desipramine-treated rats.

PMID- 8281995
TI  - In vivo interaction of neuropeptide Y and peptide YY with sigma receptor sites in
      the mouse brain.
AB  - Neuropeptide Y (NPY-(1-36)), peptide YY (PYY) and various other peptides were
      investigated for their interaction with the binding of [3H](+)-SKF10,047 to sigma
      binding sites in mouse hippocampus in vivo. NPY-(1-36), PYY-(1-36),
      [Leu31,Pro34]NPY, NPY-(2-36), and NPY-(3-36) inhibited the labelling of a
      population of haloperidol-sensitive binding sites corresponding to 35% of the
      specific binding. These in vivo binding results confirm the previous interaction
      already reported between NPY peptides and sigma binding sites.

PMID- 8281996
TI  - The atypical neuroleptic, clozapine, exerts antidystonic activity in a mutant
      hamster model. Comparison with haloperidol.
AB  - The effects of the atypical neuroleptic clozapine were studied in an inbred line
      of Syrian golden hamsters with generalized dystonia, i.e. a frequent movement
      disorder in humans. The effects of clozapine were compared with those of the
      classical neuroleptic, haloperidol. Clozapine, 7.5-20 mg/kg i.p., potently
      reduced the severity of dystonic attacks in the mutant hamster model, but induced
      marked sedation at these doses. Lower doses were ineffective. Haloperidol, 0.5
      mg/kg i.p., significantly reduced the severity of dystonia without marked
      sedation. The finding that clozapine possesses antidystonic potency similar to
      that of haloperidol in a genetic model of dystonia might suggest that this
      atypical neuroleptic is an effective alternative in the treatment of dystonic
      patients who respond to neuroleptics, particularly because of the clinical
      evidence that clozapine is almost devoid of extrapyramidal adverse effects.

PMID- 8281997
TI  - Depletion of mesolimbic dopamine during behavioral despair: partial reversal by
      chronic imipramine.
AB  - Exposure of rate to the behavioral despair test (an animal model of depression)
      for 40 min resulted in a long-lasting depletion of mesolimbic dopamine output to
      about 40% of baseline values. The decrease in extracellular dopamine was
      partially prevented by chronic pretreatment with imipramine (20 mg/kg per day
      i.p. for 21 days). The results suggest that a fall in mesolimbic dopamine output
      may be associated with depressive states and indicate that changes in the
      functional status of the dopamine system contribute to the mechanism of action of
      imipramine.

PMID- 8281998
TI  - The binding of the adenosine A2 receptor selective agonist [3H]CGS 21680 to rat
      cortex differs from its binding to rat striatum.
AB  - The binding of the reportedly A2A selective agonist CGS 21680 (2-[p-(2
      carboxyethyl)phenylethylamino]-5'N-ethylcarboxamidoadenos ine) to cortex and
      striatum was examined in parallel using quantitative receptor autoradiography.
      [3H]CGS 21680 bound to a single site in rat striatum with KD 2.3 nM and Bmax 320
      fmol/mg grey matter. In addition [3H]CGS 21680 bound to a single site in the
      cerebral cortex with KD 47 nM and Bmax 100 fmol/mg grey matter. In cat cortex
      [3H]CGS 21680 (2 nM) binding was strong and particularly evident in the most
      superficial layers. The potency order for inhibition of 2 nM [3H]CGS 21680
      binding to rat striatum was NECA (5'-N-ethylcarboxamidoadenosine; IC50 9.0 nM) >
      2-CADO (2-chloroadenosine; 87 nM) > R-PIA (N6-(R)-phenylisopropyladenosine; 110
      nM). The potency order for inhibition of 2 nM [3H]CGS 21680 binding to rat cortex
      was NECA (3.0 nM) > 2-CADO (14 nM) > or = R-PIA (16 nM). Gpp(NH)p (5'-guanylyl
      imidodiphosphate) inhibited [3H]CGS 21680 binding to both cortex and striatum,
      but more potently in cortex (IC50 100 nM vs. 470 nM). The present results show
      that there is a cortical binding site for [3H]CGS 21680 which appears to be
      different from the the striatal A2A receptor, the A2B receptor and the A1
      receptor.

PMID- 8281999
TI  - Characterization of melatonin binding sites in chicken and human intestines.
AB  - The radioligand 2-[125I]iodomelatonin was used to study melatonin binding sites
      in chicken and human intestines. In the chicken duodenum, 2-[125I]iodomelatonin
      binding sites were enriched in the musculosa layer (Bmax approximately 1 fmol/mg
      protein) as compared to the mucosa/submucosa layer (Bmax approximately 0.2
      fmol/mg protein). 2-[125I]iodomelatonin bound with a Kd of 68 +/- 18 pM (mean +/-
      S.E.M., n = 13) and was displaced by melatonin with a Ki of 0.3 nM. The Kd value
      for 2-[125I]iodomelatonin was increased 2- to 4-fold by a GTP analog, suggesting
      that the binding sites might be coupled to a G-protein. The affinity order of
      nine melatonin analogs at the enteric binding sites was in agreement with the
      pharmacological profile of melatonin receptors described in other tissues. In the
      human jejunum, 2-[125I]iodomelatonin binding could be observed in the
      mucosa/submucosa layer (Kd = 150-200 pM, Bmax = 0.7 fmol/mg protein). The
      radioligand was efficiently displaced by melatonin (Ki = 0.6 nM) but only
      marginally by N-acetyltryptamine (Ki = 22 microM) and serotonin (Ki = 14 microM).

PMID- 8282000
TI  - G proteins in aortic endothelial cells and bradykinin-induced formation of nitric
      oxide.
AB  - In bovine aortic endothelial cells (BAEC), pertussis toxin (PTx) ADP-ribosylated
      two major substrates with apparent molecular masses of 40 and 41 kDa, whereas
      cholera toxin (CTx) ADP-ribosylated two other substrates of 44 and 50 kDa. [alpha
      32P]GTP bound to three bands in the 22-27 kDa range. Immunoblot analysis revealed
      the simultaneous presence of G alpha i1, G alpha i2, G alpha i3, G alpha q or G
      alpha 11 and of different forms of G alpha s but did not detect significant
      levels of G alpha 0. Bradykinin caused a 9-fold increase in intracellular cyclic
      GMP level in BAEC (measured as an index of NO production). Preincubation of BAEC
      with CTx, but not with PTx, inhibited bradykinin-dependent production of cyclic
      GMP. These results show that G alpha s, G alpha q or alpha 11, Gi and small GTP
      binding proteins are present in BAEC and suggest that a CTx-sensitive G-protein
      (possibly either small G-protein, G alpha q or G alpha 11) could be associated
      with the bradykinin-mediated NO formation.

PMID- 8282001
TI  - Alteration of GABAA receptor alpha 1-subunit mRNA in mouse brain following
      continuous ethanol inhalation.
AB  - Alterations in the expression of mRNA for GABAA receptor alpha 1-subunit were
      analyzed in the brain using mice that had been made alcohol-dependent, and
      exhibited a decrease in GABA-dependent 36Cl- influx into membrane vesicles
      following continuous ethanol inhalation for 7 days. Continuous ethanol inhalation
      for more than 5 days induced a significant increase in the expression of GABAA
      receptor alpha 1-subunit mRNA in the brain without significantly altering total
      poly(A)+ RNA content. Furthermore, it was found that the increase in expression
      of GABAA receptor alpha 1-subunit mRNA in the brain turned to its normal level 8
      h after the ethanol inhalation was terminated. In contrast, the expression of
      beta-actin mRNA in the brain was not altered under the same experimental
      conditions. These results suggest that continuous ethanol inhalation may induce
      not only the suppression of the functions of GABAA receptor complex but also a
      reactive increase in the expression of mRNA for GABAA receptor subunits in the
      brain.

PMID- 8282002
TI  - Differential down-regulation of pulmonary beta 1- and beta 2-adrenoceptor
      messenger RNA with prolonged in vivo infusion of isoprenaline.
AB  - The down-regulation by isoprenaline of beta 1 and beta 2-adrenoceptors in rat
      lung was investigated at the receptor protein and messenger RNA level. Rats were
      treated with either isoprenaline or vehicle for 2 h, 1 day and 7 days.
      Isoprenaline treatment resulted in significant decreases of both beta 1- and beta
      2-adrenoceptor density after 1 day with maximal decreases of 65 +/- 7 and 65 +/-
      5% for beta 1- and beta 2-adrenoceptors, respectively, at 7 days. The
      administration of isoprenaline had no effect on binding affinities of either beta
      1 or beta 2-adrenoceptors. beta 1-Adrenoceptor mRNA was significantly decreased
      by 58 +/- 10, 73 +/- 4 and 51 +/- 11% at 2 h, 1 day and 7 days, respectively,
      after isoprenaline treatment. However, the beta 2-adrenoceptor mRNA was not
      changed at 2 h after treatment and was significantly decreased by 35 +/- 11 and
      45 +/- 12% at 1 day and 7 days, respectively after treatment. This time course of
      beta 2-adrenoceptor mRNA correlated well with that of the transcription factor
      cyclic AMP response element binding protein-like DNA binding activity, determined
      by gel shift assay. These findings indicate the existence of distinct mechanisms
      for down-regulation of beta 1- and beta 2-adrenoceptors and suggest the
      involvement of cyclic AMP response element binding protein in the down-regulation
      of beta 2-adrenoceptors in rat lung.

PMID- 8282003
TI  - Characterization of cardiac angiotensin AT1 receptors by [3H]SR 47436.
AB  - [3H]SR 47436, a selective and potent novel non-peptide antagonist of angiotensin
      receptors, was used to characterize the cardiac angiotensin AT1 receptors. In
      neonatal rat heart cells, Scatchard analysis showed a single class of high
      affinity binding sites (Kd = 0.24 nM, Bmax = 28 fmol/mg protein). The binding was
      saturable, reversible and prevented by angiotensin II and the AT1 subtype
      receptor antagonist DuP 753 whilst unaffected by the AT2 receptor antagonist
      PD123177. In the same cells, angiotensin II induced a twofold increase in the
      intracellular free Ca2+ concentration ([Ca2+]i), with a half-maximal effect
      (EC50) at 14 nM. This increase was prevented by SR 47436 (IC50 = 1.03 nM) and by
      the AT1 receptor antagonist DuP 753, but at higher concentrations (IC50 = 15.6
      nM) and was unaffected by PD123177. These data directly demonstrate the presence
      of cardiac AT1 receptors in rat neonatal cardiomyocytes and confirm the
      involvement of AT1 receptors in cardiac Ca2+ homeostasis.

PMID- 8282004
TI  - Pharmacological and functional characterization of human mineralocorticoid and
      glucocorticoid receptor ligands.
AB  - We characterized the pharmacological profiles of the human mineralocorticoid and
      glucocorticoid receptor for 11 natural and synthetic steroids regarding binding
      pharmacology, intracellular localization of hormone-receptor complexes, and
      agonistic or antagonistic properties at the gene expression level. The sex
      steroid progesterone bound with an affinity (ki < 0.01 nM) even higher than that
      of aldosterone to the human mineralocorticoid receptor and effectively
      antagonized the effect of aldosterone via the human mineralocorticoid receptor in
      functional co-transfection assays. This indicates that progesterone has potent
      antimineralocorticoid properties, while its antiglucocorticoid effects were less
      pronounced. The partial agonistic activities of antihormones in this assay
      suggest a direct interaction of antihormone-receptor complexes with the response
      elements on the DNA. These results are supported by immunofluorescence studies,
      in which both unliganded human mineralocorticoid and glucocorticoid receptors
      were distributed throughout the cytoplasm and nucleus, whereas agonist- as well
      as antagonist-receptor complexes showed an exclusively nuclear localization.
      These results contribute to the understanding of antihormone pharmacology and
      increase our understanding of the role of human mineralocorticoid and
      glucocorticoid receptors in physiological processes during different endocrine
      states.

PMID- 8282005
TI  - Alterations in membrane permeability induced by aminoglycoside antibiotics:
      studies on liposomes and cultured cells.
AB  - Aminoglycoside antibiotics bind to negatively-charged membranes in vitro as well
      as in vivo. We have examined if this binding could be associated with a change in
      the properties of membrane permeability. We have used a series of aminoglycoside
      derivatives and two independent test systems, namely (i) the release of calcein
      and of Mn2+ from phosphatidylinositol-containing large unilamellar vesicles, and
      (ii) the influx of Ca2+ into cultured macrophages. We found that certain
      aminoglycosides (e.g., streptomycin, isepamicin) markedly increase the membrane
      permeability whereas others (e.g., gentamicin) barely or do not influence it.
      This increase, when it occurs, is slower or less extensive than observed with
      pore-forming agents (mellitin, nystatin) or a Ca(2+)-ionophore (ionomycin). It is
      not observed with an agent [bis(beta-diethylaminoethylether)hexestrol] known to
      cause membrane fusion, and is not associated with any detectable change in
      membrane fluidity. In computer-aided conformational analysis of mixed monolayers
      between phosphatidylinositol and the aminoglycosides studied, it was found that
      those derivatives inducing an increase in membrane permeability in our
      experiments adopted an orientation rather perpendicular to the interface, whereas
      those with no or only a moderate effect were placed in a parallel orientation to
      this interface. The perpendicular orientation might cause a local condition of
      disorder which could explain the effects observed.

PMID- 8282006
TI  - Immunological reactivity of angiotensin II receptor antagonists: possible
      implications for receptor binding sites.
AB  - In the present study, we assessed the reactivity with seven anti-angiotensin II
      monoclonal antibodies of three nonpeptide and one peptide compounds described as
      selective antagonists of angiotensin II for AT1 (DuP 753, 2-n-butyl-4-chloro-5
      (hydroxymethyl)-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl] methyl] imidazole; EXP
      3174, 2-n-butyl-4-chloro-5-(carboxylic acid)-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4
      yl] methyl] imidazole) and AT2 receptor sites (CGP42112A, nicotinyl-Tyr-(N alpha
      benzyloxycarbonyl-Arg)Lys-His-Pro-Ile-OH; PD123177, 1-[(4-amino-3-methylphenyl)
      methyl]-5-(diphenyl-acetyl)-4,5,6,7-tetrahydro-1H-imidazol[4,5-c] pyridine 6
      carboxylic acid), respectively. These studies were undertaken because the
      reactivity of the monoclonal antibodies with peptide analogs of angiotensin II
      and the three-dimensional structure of an angiotensin II-immunoglobulin Fab
      fragment complex strongly suggested that the conformations identified by the
      monoclonal antibodies were relevant to those involved in receptor binding as
      defined by biophysical models supported by structure activity studies.
      Surprisingly although three of the compounds were described as competitive
      inhibitors of angiotensin II, binding of the various monoclonal antibodies to
      either ovalbumin-coupled angiotensin II adsorbed to plastic wells or 125I-labeled
      angiotensin II in liquid phase was unaffected by any of the nonpeptide
      antagonists and CGP42112A up to 10(-4) M concentration. The antagonists also
      failed to bind to rabbit polyclonal anti-angiotensin II antibodies. Direct
      binding experiments in which solid phase-immobilized angiotensin II and DuP 753
      conjugates were incubated with anti-angiotensin II or anti-DuP 753 monoclonal
      antibodies, did not show any cross-reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282007
TI  - The human and dog 5-HT1D receptors can both activate and inhibit adenylate
      cyclase in transfected cells.
AB  - The cloned human serotonin 1D (5-HT1D) receptor has been shown to inhibit
      adenylate cyclase while the corresponding cloned dog receptor has been
      characterized by its enhancement of cAMP accumulation. To resolve this apparent
      discrepancy, the human 5-HT1D receptor has been cloned and expressed in Chinese
      hamster ovary (CHO) cells and the corresponding dog receptor expressed in mutant
      Y1 adrenal (Y1 Kin-8) cells. It is shown that both receptors when activated by
      sumatriptan depress forskolin induced adenosine 3'5'-cyclic monophosphate (cAMP)
      accumulation by a pertussis toxin sensitive mechanism, presumably involving Gi
      (the adenylate cyclase inhibitory GTP transducing protein). In the absence of
      forskolin, the dog receptor enhances cAMP accumulation, thus activating Gs (the
      adenylate cyclase stimulatory GTP transducing protein). When its overriding
      action on Gi is blocked by pertussis toxin pretreatment, the human receptor also
      enhances cAMP accumulation. Thus both 5-HT1D receptors activate markedly Gi and
      to a lesser extent Gs and can exert opposite effects on the same effector system,
      adenylate cyclase.

PMID- 8282008
TI  - Characterization of [3H]losartan receptors in isolated rat glomeruli.
AB  - [3H]Losartan bound specifically to isolated rat glomeruli. Scatchard analysis
      revealed a single class of losartan binding sites with an apparent dissociation
      constant (KD) of 6.2 nM and a density of receptor sites (Bmax) of 1.2 pmol/mg
      protein. In comparison, [3H][Sar1,Ala8]angiotensin II binding sites exhibited the
      same KD value (4.3 nM), but a considerably lower Bmax (52 fmol/mg protein).
      Moreover whereas [125I][Sar1,Ala8]angiotensin II was almost equally displaced by
      angiotensin II, [Sar1,Ala8] angiotensin II and losartan, [3H]losartan was
      potently displaced by losartan only. Finally, [125I][Sar1,Ala8]angiotensin II but
      not [3H]losartan binding sites were sensitive to guanosine triphosphate (GTP)
      gamma S and Dithiothreitol. These data, together with the recent demonstration of
      intrinsic effects of losartan, support the view that [3H]losartan does not label
      only the angiotensin II type 1 receptor (AT1).

PMID- 8282009
TI  - Monoclonal antibodies against a phencyclidine derivative are used to investigate
      protein-ligand interactions.
AB  - Monoclonal antibodies against the irreversible alkylator N-ethyl-1-[2-(4
      isothiocyanothienyl)]cyclohexylamine (ITCE) of the 1-[1-(2
      thienyl)cyclohexyl]piperidine (TCP) binding site of the N-methyl-D-aspartate
      receptor were raised. Each antibody was characterized in a competition enzyme
      linked immunosorbent assay (ELISA) with a range of TCP analogs. It was found that
      each monoclonal antibody has a different affinity profile for the various TCP
      analogs. No correlation between the structure of the side chain groups of each
      compound and the selective affinities of the antibodies could be deduced,
      indicating that the overall affinity of the antibodies is determined by more than
      just the sum of the interaction forces with each ligand's functional groups. In
      addition to the possible identification of endogenous TCP-like compounds these
      antibodies could be used as a model to study the molecular interaction between
      drugs and their receptors' active sites.

PMID- 8282010
TI  - Structure-activity relationships of an endothelin ETA receptor antagonist, 50
      235, and its derivatives.
AB  - 27-O-Caffeoyl myricerone (50-235) is a nonpeptide endothelin receptor antagonist
      which is highly selective for the endothelin ETA receptor subtype. In order to
      determine which functional groups in 50-235 are essential for its activity, we
      examined the potencies of 50-235 and its derivatives to inhibit [125I]endothelin
      1 binding and endothelin-1-induced increase in the cytosolic Ca2+ concentration
      in rat aortic smooth muscle A7r5 cells. The results suggest that the 3-keto, 17
      carboxyl and 27-caffeoyl groups in 50-235 are important for ETA receptor blocking
      activity. Modifications of the catechol ring of the 27-caffeoyl group influenced
      the affinity and the functional antagonist activity, but the effects were not
      parallel.

PMID- 8282011
TI  - Extracellular ATP elevates cytoplasmatic free Ca2+ in HeLa cells by the
      interaction with a 5'-nucleotide receptor.
AB  - In the present study we have characterized the effects of ATP and several other
      nucleotides on the intracellular Ca2+ levels of HeLa cells. Using fura-2
      microscopy fluorescence measurements, the ATP-mediated increase in intracellular
      Ca2+ was shown to consist of a rapid rise which decreased after a few seconds to
      a sustained elevated level. In the absence of extracellular Ca2+ or in the
      presence of 10 microM La3+, only a transient elevation of the Ca2+ concentration
      was observed. The ATP responses were not altered after treatment of HeLa cells
      with cholera toxin or pertussis toxin. Pharmacological analysis of this calcium
      response revealed that this effect was not mediated by the classical P2y
      purinoceptor but by a 5'-nucleotide receptor.

PMID- 8282012
TI  - delta-Opioid receptor-mediated regulation of central dopaminergic neurons in the
      rat.
AB  - Effects of intraventricular injections of the delta-opioid receptor agonist [D
      Pen2,D-Pen5]enkephalin (DPDPE) and antagonist 17-cyclopropylmethyl-6,7-dehydro
      4,5-epoxy-3,14-dihydroxy-6,7,2',3'-indo l morphinan (naltrindole) hydrochloride
      were determined on the activities of mesolimbic, nigrostriatal,
      tuberoinfundibular and periventricular-hypophysial dopaminergic neurons in brains
      of male rats. Dopaminergic neuronal activity was estimated by measuring
      concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and accumulation of 3,4
      dihydroxyphenylalanine (DOPA) after administration of the decarboxylase inhibitor
      3-hydroxybenzylhydrazine in regions of the brain (nucleus accumbens, striatum,
      median eminence) and the intermediate lobe of the pituitary which contain
      terminals of these neurons. DPDPE produced a dose- and time-related increase in
      concentrations of DOPAC and accumulation of DOPA in nucleus accumbens and median
      eminence, but had no effect in striatum or intermediate lobe of the pituitary.
      Naltrindole hydrochloride had no effect per se, but blocked the ability of DPDPE
      to increase DOPAC concentrations in nucleus accumbens and median eminence. These
      results reveal that activation of delta-opioid receptors selectively increases
      the activities of mesolimbic and tuberoinfundibular but not of nigrostriatal or
      periventricular-hypophysial dopaminergic neurons.

PMID- 8282013
TI  - Behavioural and biochemical evidence that glucocorticoids are not involved in DOI
      elicited 5-HT2 receptor down-regulation.
AB  - Numerous studies have brought evidence for reciprocal relationships between
      glucocorticoids and 5-HT2 receptors; however, whether glucocorticoids affect 5
      HT2 receptor regulation is still unknown. Herein, we have analyzed whether 5-HT2
      receptor down-regulation following repeated administration of the 5-HT2/5-HT1C
      receptor agonist 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI) is affected
      by glucocorticoid removal. Compared with sham surgery, adrenalectomy (11-15 days
      beforehand) did not affect either frontal cortex [3H]ketanserin binding nor the
      number of head shakes elicited by a single administration of DOI (2.5 mg/kg
      s.c.). Pretreatment with DOI (2.5 mg/kg s.c. x 4 in 48 h) decreased to similar
      extents the head shake response to DOI injection in sham (-88%) and
      adrenalectomised (-95%) rats. Confirmingly, this paradigm was found to diminish
      the Bmax for [3H]ketanserin binding in sham and adrenalectomised rats by 64% and
      46%, respectively. From these data, it is concluded that glucocorticoid removal
      does not alter 5-HT2 receptor binding and function nor does it affect 5-HT2
      receptor down-regulation.

PMID- 8282014
TI  - Suramin selectively inhibits the non-adrenergic non-cholinergic inhibitory
      junction potential in the guinea-pig stomach.
AB  - In smooth muscle cells of the guinea-pig stomach fundus, transmural nerve
      stimulation evoked a cholinergic excitatory junction potential (e.j.p.) and, in
      the presence of atropine, a non-adrenergic non-cholinergic (NANC) inhibitory
      junction potential (i.j.p.). Suramin (> 10(-5) M), a putative inhibitor of the P2
      purinoceptor, enhanced the e.j.p. amplitude and inhibited the i.j.p., with no
      significant effect on the membrane potential. Thus, a possible involvement of ATP
      in the generation of the NANC i.j.p. has to be considered.

PMID- 8282015
TI  - Involvement of 5-HT3 receptors and vagal afferents in copper sulfate- and
      cisplatin-induced emesis in monkeys.
AB  - The emetic effects of copper sulfate and cisplatin and the potential involvement
      of vagal afferent fibers and 5-HT3 receptors in the emesis were investigated in
      cynomolgus monkeys. Retching and vomiting induced by both oral (100 mg/kg) and
      intravenous (20 mg/kg) copper sulfate were inhibited markedly by abdominal
      vagotomy. Furthermore, the emetic response induced by oral copper sulfate was
      strongly inhibited by intravenous ICS 205-930 (0.1 mg/kg), a 5-HT3 receptor
      antagonist. Cisplatin (3 mg/kg, i.v.) caused severe retching and vomiting, and
      the number of emetic responses was much greater than that in other species. The
      emetic response induced by cisplatin was inhibited markedly by abdominal vagotomy
      or concurrent administration of ICS 205-930 (3 x 0.1 mg/kg, i.v.). These results
      suggest that the monkey is more sensitive to cisplatin than other species and
      that the vagal afferent terminals and 5-HT3 receptors play an important role in
      the emetic response induced by copper sulfate and cisplatin.

PMID- 8282017
TI  - Further assessment of the antagonist properties of the novel and selective 5-HT1A
      receptor ligands (+)-WAY 100 135 and SDZ 216-525.
AB  - In vitro biochemical and electrophysiological methods were used to assess the
      potential antagonist properties of the novel compounds (+)-WAY 100 135 [N-tert
      butyl-3,4-(2-methoxyphenyl)piperazin-1-yl-2- phenylpropanamide dihydrochloride]
      and SDZ 216-525 [methyl 4-(4-(4-(1,1,3-trioxo-2H-1,2-benziosothiazol-2-yl)butyl)-
      1-piperazinyl)1H-indole-2-carboxylate] at pre- (i.e. somatodendritic
      autoreceptors) and postsynaptic 5-HT1A receptors in the rat brain. Both (+)-WAY
      100 135 and SDZ 216-525 were pure antagonists at postsynaptic 5-HT1A receptors
      negatively coupled to adenylate cyclase in rat hippocampal membranes. Competitive
      prevention of the inhibition by the 5-HT1A receptor agonists 8-OH-DPAT [8-hydroxy
      2-(di-n-propylamino)tetralin], 5-HT (5-hydroxytryptamine), S-20499 [(+)-4-(N-(5
      methoxychroman-3-yl)-N-propylamino)butyl-8-azaspir o(4,5)decane- 7,9-dione] and
      lesopitron occurred with a pA2 of 8.7 for (+)-WAY 100 135 and 9.9 for SDZ 216
      525. The higher potency of the latter compound was also noted at the level of
      presynaptic 5-HT1A receptors where both (+)-WAY 100 135 and SDZ 216-525 prevented
      the negative influence of 5-HT1A receptor agonists (8-OH-DPAT, flesinoxan or
      lesopitron) on the nerve impulse flow within dorsal raphe nucleus 5-HT neurones
      in brain stem slices. At high concentrations, both (+)-WAY 100 135 (> 1 microM)
      and SDZ 216-525 (> or = 0.1 microM) inhibited the spontaneous cell discharge
      through different mechanisms. The blockade of alpha 1-adrenoceptors by (+)-WAY
      100 135 apparently accounted for its inhibitory influence on the firing of 5-HT
      neurones, whereas 5-HT1A receptor agonist properties were responsible for the
      effect of SDZ 216-525. Although approximately 10 times less potent than SDZ 216
      525, (+)-WAY 100 135 is therefore a pure antagonist at both pre- and postsynaptic
      5-HT1A receptors in the rat brain.

PMID- 8282016
TI  - Effects of KRN2391, a novel vasodilator, on pancreatic exocrine secretion in
      anesthetized dogs.
AB  - The effects of KRN2391, a newly synthesized vasodilator, on pancreatic exocrine
      secretion in anesthetized dogs were compared with those of Ki3315, pinacidil and
      nitroprusside. Graded doses of KRN2391 (0.03-3 mumol/kg) and nitroprusside (0.003
      0.3 mumol/kg) injected i.a. produced dose-dependent increases in the secretion of
      pancreatic juice, with a high concentration of protein and low concentration of
      bicarbonate, but Ki3315 or pinacidil did not (up to 10 mumol/kg). KRN2391 and
      nitroprusside increased the cyclic GMP levels in pancreatic tissue together with
      the increase in pancreatic secretion. Methylene blue decreased pancreatic
      secretion and cyclic GMP levels stimulated by KRN2391 and nitroprusside, but
      glibenclamide did not. KRN2391, Ki3315, pinacidil and nitroprusside caused
      vasodilator actions. These results suggest that KRN2391 has direct secretory
      properties on pancreatic exocrine glands of the dog and its nitro moiety has an
      important role in the stimulation of pancreatic secretion, but the K+ channel
      opening action or increasing of blood flow rate does not participate in the
      secretion.

PMID- 8282018
TI  - Benzodiazepine receptor equilibrium constants for flumazenil and midazolam
      determined in humans with the single photon emission computer tomography tracer
      [123I]iomazenil.
AB  - This study is based on the steady state method for the calculation of Kd values
      recently described by Lassen (J. Cereb. Blood Flow Metab. 12 (1992), 709), in
      which a constant infusion of the examined nonradioactive ligand is used with a
      bolus injection of tracer. Eight volunteers were examined twice, once without
      receptor blockade and once with a constant degree of partial blockade of the
      benzodiazepine receptors by infusion of nonradioactive flumazenil (Lanexat) or
      midazolam (Dormicum). Single photon emission computer tomography and blood
      sampling were performed intermittently for 6 h after bolus injection of
      [123I]iomazenil. The tracer in plasma was determined by high-pressure liquid
      chromatography and also by a simple octanol extraction procedure. The free
      concentration of flumazenil and midazolam in plasma water averaged 52% and 3.5%
      of that in whole plasma. The Kd values for the entire cortical rim for flumazenil
      were 7.4, 10.0, 10.3 and 17.7 nmol/l plasma water and, for midazolam, 73, 76, 58
      and 30 nmol/l plasma water. The variation exceeds random methodological error and
      is probably due to interindividual differences in receptor affinity. The Kd level
      of midazolam is considerably higher than expected from the results of in vitro
      studies.

PMID- 8282019
TI  - Effects of two Ca2+ modulators in normal and albumin-sensitized guinea-pig
      trachea.
AB  - The voltage-dependent Ca2+ channel blocker, verapamil, and the calmodulin
      antagonist, trifluoperazine, each reduced resting tone and attenuated
      constriction induced by acetylcholine or vagal stimulation in normal guinea-pig
      trachea. Attenuation of vagal responses involved both pre- and post-junctional
      effects on cholinergic neurotransmission. In albumin-sensitized trachea both
      drugs caused small increases in resting tone. Vagally mediated constrictor
      responses were resistant to attenuation by verapamil in sensitized trachea.
      Trifluoperazine was less effective against acetylcholine-induced tone in
      sensitized, as compared to untreated, trachea. The results indicate that Ca2+
      handling is altered in airway smooth muscle in this animal model of bronchial
      asthma. Abnormal Ca2+ handling, therefore, may underlie the hyperresponsiveness
      to vagal input exhibited in sensitized trachea and could contribute to the
      generalised airway hyperreactivity characteristic of asthma.

PMID- 8282020
TI  - Effect of idebenone on adenosine outflow and adenine nucleotide level in
      hippocampal slices under ischemia-like conditions.
AB  - The effect of idebenone on the changes in adenosine and nucleotide metabolism
      occurring in hippocampal slices after ischemia-like conditions (superfusion with
      glucose-free Krebs solution gassed with 95% N2-5% CO2) and during reperfusion
      with normal Krebs solution was investigated by measuring adenosine and inosine
      outflow, and adenosine and adenine nucleotide levels by HPLC. Five minutes of
      ischemia-like conditions brought about an 8- and 4-fold increase in adenosine and
      inosine outflow 10 min after reperfusion and a 75% increase in the tissue level
      of adenosine, a 40% decrease in ATP, and a 50% increase in AMP at the end of the
      ischemic period. Ten minutes after reperfusion, ATP and AMP returned to control
      values. Idebenone (25-100 microM) brought about a concentration-dependent
      increase in adenosine and inosine outflow evoked by ischemia-like conditions.
      Idebenone (50 microM) also increased the adenosine content in hippocampal slices
      after both ischemia (+150%) and reperfusion (+320%). An 82% increase in ADP, 174%
      in AMP, and 56% in the total sum of nucleotides, 10 min after reperfusion were
      found in idebenone treated slices. These results suggest that idebenone enhances
      adenosine formation after ischemia-like conditions from sources other than AMP,
      and improves phosphorylating activity during reperfusion. Idebenone, by
      increasing adenosine and total nucleotide levels, may protect brain tissue from
      ischemic damage.

PMID- 8282021
TI  - Cerebrovascular effects of NG-nitro-L-arginine methylester are conserved under
      halothane anaesthesia.
AB  - The effects of the nitric oxide synthesis inhibitor NG-nitro-L-arginine
      methylester (L-NAME) on mean arterial blood pressure (MABP) and local cerebral
      blood flow were determined in conscious and halothane-anaesthetised rats. Thirty
      minutes post-drug administration in conscious rats L-NAME (30 mg kg-1 i.v.)
      induced significant hypertension (MABP 132 +/- 2 mmHg and 163 +/- 6 mmHg (means
      +/- S.D.) for saline and L-NAME groups respectively) and significant
      hypoperfusion throughout the brain (mean +/- S.D. reduction in cerebral blood
      flow 27.3 +/- 5.9% compared with controls). In contrast, under halothane
      anaesthesia, L-NAME did not significantly change MABP but significant reductions
      in cerebral blood flow (43.2 +/- 3.7%) were observed. Thus the cerebrovascular
      response to L-NAME is conserved under halothane anaesthesia despite attenuation
      of the peripheral vasoconstrictive action.

PMID- 8282022
TI  - Comparison of the behavioral effects of ibogaine from three sources: mediation of
      discriminative activity.
AB  - Ibogaine is an alkaloid employed for its hallucinatory properties in West Central
      Africa which has been the subject of alleged efficacy as an aid in the
      interruption and treatment of chemical dependency. The major sources of the
      Schedule I agent are: Sigma Chemical Co., the National Institute on Drug Abuse
      and as NDA International Inc.'s Endabuse. The intent of the present study was to,
      for the first time, train rats to discriminate the interoceptive stimuli produced
      by (10 mg/kg, intraperitoneally administered) ibogaine. Once trained, these rats
      were used to investigate the dose-response effects to ibogaine from each of the
      three suppliers. In addition, stimulus generalization to the dopamine antagonist
      CGS 10476B, as well as to the serotonergically active compounds fenfluramine,
      TFMPP (1-(m-trifluoromethylphenyl)piperazine, DOI (1-(2,5-dimethoxy-4-iodophenyl)
      2-aminopropane), MDMA (3,4-methylenedioxymethamphetamine), quipazine and LSD, was
      tested. The results indicate that ibogaine is readily discriminable from its
      vehicle and that ibogaine from each of the three supplies produced statistically
      similar discrimination with ED50 values ranging from 2.5 to 3.4 mg/kg. In
      addition, various doses of the novel drugs tested produced, at best, intermediate
      ibogaine-appropriate responding and, thus, no drug tested can be considered to
      generalize to ibogaine-like stimuli. Discussion concerns the multiple actions of
      ibogaine that have been cited in the scientific literature. The similarity in
      potency of ibogaine from three potential suppliers should allow for pre-clinical
      work using any of these research samples to be comparable.

PMID- 8282023
TI  - Renal actions of the selective angiotensin AT2 receptor ligands CGP 42112B and PD
      123319 in the sodium-depleted rat.
AB  - The purpose of this study was to investigate the renal actions of the new
      selective angiotensin AT2 receptor ligands, CGP 42112B and PD 123319, in
      comparison to those of the AT1 receptor antagonist losartan, in the sodium
      depleted, anesthetized rat. Losartan (1, 3 and 10 mg/kg i.v.) produced a dose
      dependent decrease in blood pressure and renal vascular resistance that was
      statistically significant. Effective renal blood flow tended to increase in
      response to all doses of losartan while glomerular filtration rate either did not
      change or decreased, leading to a significant fall in filtration fraction.
      Losartan did not induce significant changes in urine volume, urinary sodium
      excretion, urinary potassium excretion or free water formation. The selective AT2
      receptor ligand CGP 42112B at infusion rates of 1-100 micrograms/kg per min i.v.
      had no significant effect on blood pressure or any measured parameter of renal
      function. However, when infused at 1000 micrograms/kg per min i.v., CGP 42112B
      did not affect blood pressure, but significantly increased effective renal blood
      flow, glomerular filtration rate, urinary sodium excretion, urinary potassium
      excretion and free water formation, while significantly decreasing renal vascular
      resistance. The selective AT2 receptor ligand PD 123319 at infusion rates between
      1 and 100 micrograms/kg per min i.v. also had no significant effect on blood
      pressure or on any measured parameter of renal function. However, at an infusion
      rate of 1000 micrograms/kg per min i.v., PD 123319 tended to increase renal
      vascular resistance, urinary sodium excretion, urinary potassium excretion and
      free water formation, and to decrease effective renal blood flow, although none
      of these changes reached a level of statistical significance.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8282024
TI  - Digital image analysis of cultured rat lens during oxidative stress-induced
      cataractogenesis.
AB  - Isolated rat lenses were exposed to oxidative stress generated by 100 microM
      H2O2, 2 mM ADP and 100 microM ferrous ammonium sulfate. Oxidation-induced
      cataract formation was followed by measuring loss of transmitted light intensity
      using quantitative digital image analysis, which offers distinct advantages over
      conventional photography. In the presence of oxidants, total and average light
      transmitted by the lens decreased exponentially as a function of time; the cortex
      showing a greater rate of decline in transmitted light intensity than the
      nucleus, which led to a change in the distribution pattern of light intensity.
      Lenses developing oxidative cataracts also showed a significant increase in
      diameter and an increase in the total wet weight. Maximal increase in lens
      diameter preceded maximal decrease in light intensity. These studies demonstrate
      the utility of quantitative image analysis in studying changes in lens geometry
      and transparency, and suggest that cataract formation is a single rate process.

PMID- 8282025
TI  - Regulation of the interphotoreceptor retinoid-binding protein content of the
      retina by vitamin A.
AB  - A retinoid-binding protein has been identified in the extracellular space that
      separates the photoreceptor cells and the retinal pigment epithelium (RPE) of the
      mammalian retina. This protein (interphotoreceptor retinoid-binding protein,
      IRBP) appears to be involved in the transport of visual cycle retinoids between
      the photoreceptors and the RPE. Experiments were conducted to evaluate the
      possibility that the amount of IRBP in the retina is regulated by the
      availability of retinoids in the retina. Rats were fed diets containing vitamin A
      either in the form of retinyl palmitate (+A), which can be metabolically
      converted into the retinoids involved in vision, or retinoic acid (-A), which
      does not support visual function. After 23 weeks, when rhodopsin levels had
      declined by over 90% in the -A rats, some animals in the latter group were given
      a single intramuscular injection of all-trans retinol. Both 1 day and 1 week
      later, the IRBP immunoreactivities in the retinas from the treated rats were
      determined with quantitative immunocytochemistry. IRBP immunolabeling densities
      were also determined in the +A and -A groups. Retinas of animals that had
      consumed the -A diet for 23 weeks bound an average of 50% less anti-IRBP antibody
      in the retina than rats that had been fed the +A diet for the same period. One
      day after retinol administration, the mean IRBP immunolabeling density had
      returned to that observed in the +A rats. The restored level of IRBP
      immunoreactivity was maintained 1 week after injection. The immunocytochemical
      findings were confirmed by immunoblot analysis of eyecup homogenates.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8282026
TI  - Surface and intracellular pools of Na,K-ATPase catalytic and immuno-activities in
      rat exorbital lacrimal gland.
AB  - The subcellular distribution of Na,K-ATPase in rat lacrimal gland acinar cells
      was surveyed by subcellar fractionation followed by determination of two Na,K
      ATPase catalytic activities, K(+)-dependent p-nitrophenylphosphate hydrolysis and
      ouabain-sensitive ATP hydrolysis, by Western blotting of isolated membrane
      fractions, and by analysis of lacrimal tissue with immunocytochemical methods at
      the light and EM levels. Both catalytic activities distributed in parallel after
      centrifugation on sorbitol gradients. They were associated with membrane samples
      that appeared to be derived from: (1) acinar cell basal-lateral membranes; (2)
      the Golgi complex; and (3) endocytic compartments. beta 1-subunit
      immunoreactivity closely paralleled catalytic activity. The alpha 1-subunit
      immunoreactivity distribution suggested the presence of alpha 1-subunits in alpha
      beta complexes and excess alpha 1 subunits which were not assembled with beta
      subunits and not catalytically active. In the putative basal-lateral membrane and
      endocytic samples, alpha 1-reactivity was associated primarily with a 100-kDa
      band, while in the Golgi samples it was associated primarily with 40 and 60-kDa
      bands. beta 1-reactivity was also heterogeneous, with reactivity in basal-lateral
      membrane and putative endocytic samples associated with a broad band of 50-54
      kDa, and reactivity in Golgi samples associated with discrete bands of 50, 52,
      and 54 kDa. Staining with anti-holoenzyme and anti-alpha 1-subunit antibodies
      yielded strong indirect immunofluorescence signals both in plasma membrane and in
      intracellular regions of acinar cells. beta 1-like immunoreactivity was
      concentrated in cytoplasmic regions of acinar cells. Immunogold electron
      microscopy revealed positive staining with anti-holoenzyme in Golgi membranes of
      acinar cells and in basal-lateral membranes of duct cells. These data support the
      hypothesis that lacrimal acinar cells contain substantial cytoplasmic pools of
      Na,K-ATPase and that there is a location-dependent heterogeneity which is not
      detected by immunocytochemical methods.

PMID- 8282027
TI  - Prejunctional receptors and second messengers for angiotensin II in the rabbit
      iris-ciliary body.
AB  - Angiotensin II has been shown to act prejunctionally to facilitate sympathetic
      neutrotransmission in various tissues including the iris-ciliary body. In the
      present study, we characterized the prejunctional angiotensin II receptor subtype
      and its signal transduction pathway in the rabbit iris-ciliary body. Angiotensin
      II caused concentration-dependent facilitation of electrically evoked [3H]
      norepinephrine overflow from the isolated, superfused rabbit iris-ciliary body
      without affecting basal tritium efflux. Responses to angiotensin II were
      antagonized by saralasin and DuP753 but not by PD123177 indicating that
      prejunctional angiotensin II receptors of the AT1-subtype mediate the
      facilitation of evoked [3H]-norepinephrine release. The non-selective cyclic
      nucleotide phosphodiesterase inhibitor, isobutylmethyl xanthine enhanced the
      angiotensin II response whereas the cAMP-specific phosphodiesterase inhibitor, RO
      20-1724 had no effect. In the presence of 8-bromo-cGMP, responses elicited by
      angiotensin II were significantly (P < 0.01) greater than that caused in the
      absence of 8-bromo-cGMP. In contrast, 8-bromo-cAMP had no effect on the
      angiotensin II-induced response. Guanylate cyclase inhibitors, methylene blue and
      LY83583 abolished angiotensin II-induced enhancement of [3H]-norepinephrine
      overflow without affecting basal tritium efflux. Taken together, these results
      suggest that cGMP could be involved in the angiotensin II response. Neither
      phospholipase C inhibitors (neomycin, 2-nitro-4-carboxyphenyl-N,N-diphenyl
      carbamate and phenylmethylsulfonyl fluoride) nor an inhibitor of protein kinase C
      (staurosporine) had any significant effect on the angiotensin II response,
      indicating that metabolites of inositol phospholipid metabolism or activation of
      protein kinase C are not involved in the response to this peptide.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8282028
TI  - Persistent hyaloid vascular system in age-related cataract in a SAM strain of
      mouse.
AB  - The cataractogenesis of age-related cataract in a strain of Senescence
      Accelerated Mouse; SAM-P/9 was investigated. In the mature cataract, funnel
      shaped tissue of the persistent hyaloid vascular system extended from the retinal
      papilla and covered the extremely protruding posterior pole of the cataractous
      lens, as seen using a stereomicroscope. Longitudinal examination of the eyes with
      transparent lenses using an ophthalmoscope revealed that the hyaloid vascular
      system persisted in about 90% of the 5-week-old mice, at least unilaterally. The
      eyes with transparent lenses in some old mice retained this tissue and a
      retrospective study revealed that cataract never occurred in eyes without this
      tissue. Microphthalmos was not observed. Histologically, in the eyes with
      transparent lenses, the posterior lens capsule covered with a hyaloid vascular
      system became very thin but only a few lens fibre cells just inside the capsule
      had swelled. In the lens of the mature cataract or even with initial changes, the
      lens capsules ruptured. Electron microscopic examination showed that the
      persistent hyaloid vascular system was tissue consisting of capillary and
      mesenchymal cells. These observations suggest that the persistent hyaloid
      vascular system is a necessary but not sole factor for age-related cataract
      formation in SAM-P/9, and that other age-related factors probably have a role.

PMID- 8282029
TI  - Hyaluronan injected in the anterior chamber of the eye is catabolized in the
      liver.
AB  - Catabolism of hyaluronan was studied by injecting hyaluronan (M(r) 200,000)
      labelled with [125I]-tyramine cellobiose, ([125I]-TC), into the anterior chamber
      of the rabbit eye. After endocytosis [125I]-TC accumulates in cells, allowing
      localization of the site of catabolism. When 0.1 ml of the aqueous humour was
      replaced with an equal volume containing polymer in tracer quantities, 24% was
      recovered from the eye at 2 hr and 6.5% at 6 hr after injection. With replacement
      of 0.2 ml of aqueous humour 38% and 19%, respectively, were found within the eye
      at the same time points. Most of the radioactivity was found in the liver. If the
      tracer was mixed with Healon the removal from the anterior chamber was delayed.
      Chromatography on Sephacryl S-300 showed that there was no significant
      degradation of the labelled polymer in the aqueous humour nor in the remaining
      parts of the enucleated eye, while most of the tracer extracted from the liver
      was of low molecular weight. Thus the labelled hyaluronan was being washed out of
      the eye and subsequently taken up and catabolized by the liver.

PMID- 8282030
TI  - Adrenoceptor subtypes involved in neurally evoked sympathetic vasoconstriction in
      the anterior choroid of cats.
AB  - Electrical stimulation of the preganglionic cervical sympathetic nerve produced
      ocular vasoconstrictor responses as measured from the anterior choroid of
      anesthetized cats using laser-Doppler flowmetry. Ipsilateral nictitating membrane
      contractions were simultaneously measured as an established index of neural
      sympathetic activation. The frequency-response relationships for both effectors
      were nearly linear from 0.125-32 Hz. When elicited at 2-min intervals, submaximal
      evoked responses of both systems were stable for more than 1 hr. Ocular
      vasoconstrictor and nictitating membrane responses were blocked in a dose
      dependent fashion by intravenous treatment with the non-selective alpha
      adrenoceptor antagonist phentolamine (0.1-3.0 mg kg-1) and with phenoxybenzamine
      (3.0 mg kg-1) as well as with the selective alpha 1-adrenoceptor antagonist,
      prazosin (10-300 micrograms kg-1). In contrast, neither evoked response was
      antagonized by alpha 2-adrenoceptor blocker, yohimbine (10-300 micrograms kg-1),
      nor with rauwolscine (500 micrograms kg-1). No significant alteration in
      magnitude of ocular vasoconstriction was seen with blockade of either muscarinic
      (atropine, 1 mg kg-1) or beta-adrenergic (propranolol, 1 mg kg-1) receptors.
      These results demonstrate the usefulness of laser-Doppler flowmetry in studies of
      the choroidal circulation and suggest that, as previously established for the
      nictitating membrane, adrenergic neurogenic vasoconstriction in the anterior
      segment of the eye is mediated almost exclusively by alpha 1-adrenoceptor
      mechanisms.

PMID- 8282031
TI  - Experimental light damage increases lipofuscin in the retinal pigment epithelium
      of Japanese quail (Coturnix coturnix japonica).
AB  - Lipofuscin accumulation in the retinal pigment epithelium (RPE) of Japanese quail
      was investigated in normal and light-damaged animals at 4 months and 12 months of
      age following a single, 18-hr light-damaging exposure (3000-3200 lx) evaluated 6
      weeks postexposure. Quail in a second experimental group light-damaged at 4
      months of age were exposed to a second, identical light-damaging exposure at 12
      months of age. RPE lipofuscin was quantitatively assessed in three ways: (1)
      total lipofuscin, expressed as a percentage of the basal RPE cell area, (2) mean
      number of lipofuscin granules per RPE cell, and (3) mean area of lipofuscin
      granules. At 12 months of age, control female RPE cells showed substantially more
      lipofuscin than did males. Animals that received a single damaging light-exposure
      showed no significant differences in lipofuscin at either age when compared with
      controls, and none were observed between males and females. However, in the
      double light-exposure condition, both total lipofuscin and the number of
      lipofuscin granules were significantly higher in females compared to controls and
      also, when compared with animals in the single light-exposure condition. Mean
      lipofuscin granule size decreased in females in the double light-exposure
      condition when compared with control values. Histopathological evaluation of
      photoreceptor outer segments and outer nuclear layer indicated that double
      exposed, 12-month-old females showed the most severe effects, including a
      substantial decrease (70%) in rod photoreceptor densities. However, only a small
      change was observed in cone densities for either sex (12-15%) in this condition.
      Overall, a strong, negative correlation (r = -0.78) was obtained between total
      lipofuscin and average rod density across age, sex, control and experimental
      conditions. A somewhat greater correlation (r = -0.82) was obtained for females,
      alone. These results suggest that rods, when severely damaged by light exposure,
      contribute to increased RPE lipofuscin. Age, sex and light-exposure history
      appear to be critical variables that can influence both the amount of lipofuscin
      present in RPE cells as well as the relative vulnerability of rod and cone
      photoreceptors to cumulative light-exposure damage. These results have
      implications for the development of a variety of age-related changes and diseases
      of the outer retina, including age-related macular degeneration.

PMID- 8282032
TI  - Corticosteroid treatment and trabecular meshwork proteases in cell and organ
      culture supernatants.
AB  - Steroid-induced glaucoma is believed to result from increased aqueous outflow
      resistance and evidence suggests that this is the result of an excess
      accumulation of extracellular matrix components. This accumulation could result
      from an imbalance in the natural turnover of these components. We have
      investigated the effect of corticosteroid treatment of trabecular meshwork (TM)
      organ and cell cultures on the extracellular activities of the matrix
      metalloproteinases and plasminogen activators. We find that corticosteroid
      treatment results in decreased extracellular activity of stromelysin and tissue
      plasminogen activator in trabecular meshwork cell culture, and decreased 92 kDa
      collagenase IV, stromelysin, and tissue plasminogen activator in trabecular
      meshwork organ culture. These data suggest that decreased levels of proteolytic
      activities could account, in part, for the accumulation of some extracellular
      matrix components and be a contributing mechanism in steroid-induced glaucoma.

PMID- 8282033
TI  - Morphological changes in human nuclear cataracts of late-onset diabetics.
AB  - The ultrastructure of human diabetic lens nuclei is described for the first time.
      Two cataractous lenses from late-onset diabetics were examined using transmission
      electron microscopy to determine the type and distribution of cellular
      disruptions. The diabetic lens nuclei were compared to a transparent nucleus from
      a normal human lens. Cellular damage to the exterior region of the diabetic lens
      nuclei was extensive, especially at the cortical-nuclear interface. Areas of lens
      fiber condensation as well as areas of cytoplasmic loss were observed in the
      outer nucleus. Morphological defects commonly seen in this region included:
      multilamellar membrane aggregates, voids where cytoplasmic material was lost,
      deposits in the extracellular spaces, density variations between adjacent fiber
      cells, and heterogeneously staining globules. The opaque central regions of the
      nuclei displayed relatively little cell damage, but fiber cells were very
      irregular in shape and packing. The ultrastructure of inner nuclear fiber cells
      was comparable to that seen in the normal lens and in age-related nuclear
      cataracts in non-diabetics. It appears that the effect of hyperglycemia on lens
      fiber cells is dependent on their age and stage of differentiation.

PMID- 8282034
TI  - The measurement of intracellular sodium ion concentration in the horizontal cells
      of the stingray retina.
AB  - Membrane potentials, and intracellular concentrations of sodium ions in the
      horizontal cells of the stingray retina were measured directly by means of ion
      selective microelectrodes. The electrodes used were of the double-barreled type
      and bis[(12-crown-4)methyl]methyldodecylmalonate was used as the ion-selective
      resin. The average intracellular concentration of Na+ ions in the horizontal
      cells and the extracellular concentration of Na+ ions near the horizontal cells
      were 123 mM and 351 mM, respectively (n = 27). The equilibrium potential was
      estimated to be +27.3 mV. Although each value of the equilibrium potential was
      scattered over a wide range, they were always positive regardless of the membrane
      potential. This was the first direct measurement of the sodium ion-concentration
      for the retinal horizontal cells. The results support the idea that the origin of
      the dark depolarization of the stingray horizontal cell is caused by the
      glutamate-induced high-sodium conductance of the membrane.

PMID- 8282035
TI  - Early epithelial lesions in cataracts of GSH-depleted mouse pups.

PMID- 8282036
TI  - The effect of prostaglandin E2 on corneal inflammation in the rat.

PMID- 8282037
TI  - Short-wave sensitive cones in the rodent retinas.

PMID- 8282038
TI  - The UPL rat: a new model for hereditary cataracts with two cataract formation
      types.

PMID- 8282039
TI  - Changes in crystallin expression during transdifferentiation and subsequent
      ageing of embryonic chick neural retina in vitro: comparison with lens
      epithelium.
AB  - We have shown that cultured day-old chick lens epithelial cells undergo changes
      in crystallin expression during lens fibre (lentoid body) differentiation and
      ageing in serial subculture which are similar to those found in the adult lens in
      vivo. Here we have maintained neural retina cells, which transdifferentiate in
      vitro, for 250 days in serial subculture, in order to determine whether the
      tissue of origin affects the sequence of changes in crystallin expression and
      capacity for lentoid body formation both during fibre formation in primary
      culture and ageing in vitro. Alpha and beta-crystallins were detectable before
      delta-crystallin in primary cultures of both day-old chick lens epithelium and
      neural retina from 8-day embryos, but while beta 2 (26 kDa) was detected in pre
      lentoid lens epithelial cultures it was not detected until after lentoids formed
      in neural retina cultures. The relative proportions of the alpha- and beta
      crystallin polypeptides were similar in lentoid-rich lens epithelium and neural
      retina cultures, and both cultures underwent similar changes in serial
      subculture: a loss of lentoid forming capacity, an early preferential loss of
      delta-crystallin expression followed by a failure to accumulate first alpha- and
      then beta-crystallins. The order in which the beta-crystallin polypeptides were
      lost differed between the cultures. There is evidence for rapid turnover of alpha
      and beta-crystallins while actin is the major component expressed in both types
      of aged cultures. Thus lens and retinal cells show some initial differences in
      the sequence of crystallin expression in primary cultures and in the eventual
      characteristics of aged cultures, but during the period beginning with lentoid
      formation and ending with the onset of senescence, lens cells from either source
      follow a broadly similar programme of ageing changes which are similar to those
      which occur during lens ageing in vivo.

PMID- 8282040
TI  - Corneal endothelial cell matrix promotes expression of differentiated features of
      retinal pigmented epithelial cells: implication of laminin and basic fibroblast
      growth factor as active components.
AB  - Human retinal pigmented epithelial (RPE) cells cultured on plastic, unlike RPE in
      situ, often fail to density arrest, do not produce melanin, and do not express
      mRNA for cellular retinaldehyde binding protein (CRALBP). When human RPE are
      cultured on the extracellular matrix produced by bovine corneal endothelial cells
      for 1 week or human RPE for 3 weeks, they density arrest, assume a differentiated
      morphology, and produce pigment and mRNA for CRALBP (all differentiated features
      of RPE). Human RPE grown on a laminin substratum or grown in media supplemented
      with basic fibroblast growth factor (basic FGF), assume a differentiated
      morphology for up to 3 weeks, and this is maintained for several months when the
      cells are grown on laminin in the presence of basic FGF and heparin. With the
      latter conditions, the cells also produce mRNA for CRALBP. Human RPE grown on
      bovine corneal endothelial cell matrix treated with neutralizing antibodies to
      basic FGF or laminin or agents that displace FGF from extracellular matrix
      (suramin or protamine), do not assume a differentiated morphology and express
      less CRALBP mRNA than RPE grown on bovine corneal endothelial cell matrix treated
      with antibodies to type IV collagen. These data suggest that the extracellular
      matrix may facilitate RPE expression of differentiated features and that laminin
      and basic FGF may be important components.

PMID- 8282041
TI  - Low levels of inorganic mercury damage the corneal endothelium.
AB  - The effect of inorganic mercury on the integrity of the endothelium of isolated
      bullfrog (Rana catesbeiana) corneas was examined by spectrophotometric analysis
      of corneal uptake of the vital stain Janus green, and by both transmission (TEM)
      and scanning (SEM) electron microscopy. The uptake of Janus green by the
      endothelium is dose related between 1.0 and 30.0 microM HgCl2. The effect of
      mercury is not altered by changes in external calcium concentration, nor is it
      influenced by the calcium ionophore A23187, indicating that inorganic mercury
      damages the corneal endothelium through a mechanism which does not involve
      competition with external calcium or interaction with calcium channels. TEM and
      SEM demonstrate significant ultrastructural damage to the endothelium exposed to
      inorganic mercury, including cellular swelling, increased vacuolization, focal
      denuding of Descemet's membrane, and diminished integrity at the intercellular
      junctions.

PMID- 8282042
TI  - Effects of antiglaucoma medications on bovine trabecular meshwork cells in vitro.
AB  - Using an in vitro culture system, we investigated the effects of five
      antiglaucoma drugs on growth and morphologic characteristics of bovine trabecular
      meshwork cells. Epinephrine hydrochloride (55-550 microM) and pilocarpine
      hydrochloride (0.8-16 mM), when added to the cultures for 3 days, inhibited
      trabecular cell growth in a dose-dependent manner. The lowest concentration at
      which the inhibitory effect was observed was 109 microM and 0.8 mM, respectively,
      for epinephrine and pilocarpine. Dipivefrin hydrochloride (26-260 microM),
      timolol maleate (116-1160 microM), and levobunolol hydrochloride (150-1500
      microM) were also added to the cells for 3 days. These drugs caused a reduction
      in cell density, respectively, at concentrations higher than 103, 460, and 616
      microM. Cell elongation was seen in cultures treated with epinephrine and
      dipivefrin, whereas levobunolol and timolol induced the cells to adopt a rounded
      appearance. Cells that had been exposed to pilocarpine were enlarged with
      numerous vacuoles. By scanning electron microscopic techniques, epinephrine,
      timolol, and levobunolol were found to retard the phagocytosis of latex beads by
      trabecular meshwork cells. Immunostaining with the use of antibodies to vimentin
      and actin revealed disorganization and condensation of cytoskeletal fibers in
      trabecular meshwork cells after treatment with epinephrine and dipivefrin. Little
      change was seen with comparable concentrations of a preservative, benzalkonium
      chloride, and a vehicle, Liquifilm tears. These results showed that antiglaucoma
      drugs, depending on their concentrations, may profoundly influence the growth and
      activity of trabecular meshwork cells.

PMID- 8282043
TI  - Histopathological study of hereditary cataractous lenses in SCR strain rat.
AB  - A new cataractous rat strain, Shumiya Cataract Rat (SCR), which was derived from
      the cross-breeder formed between the spontaneous hypertensive rat and the Zucker
      fatty rat, was studied by light and electron microscopy. The earliest change was
      the occurrence of some displaced nuclei in the posterior cortical fibres at
      birth. By 2 weeks of age, mild dysplasia of the anterior suture, aggregated
      epithelial cells overlying the sutural area, and poorly differentiated epithelial
      cells at the bow area were observable. At 3 weeks, unusually dense lens fibres
      near dense epithelial cells were found at the equator, and some epithelial cells
      showed accellularity after 4 weeks. Swelling and liquefaction of the lens fibres
      appeared in the anterior cortex by this stage. By 6 weeks, these changes extended
      toward the equatorial region. At 7 weeks, a sutural gap occurred at the anterior
      polar area, and this gap reached a maximum at 8 weeks. At this time, swelling of
      the posterior extremities of the lens fibres appeared, showing a small placoid
      opacity of the posterior subcapsular region under a dissecting microscope. At 10
      weeks, small amounts of liquefaction were observed in this region. Between 10.5
      and 11 weeks, as the posterior suture of liquefaction were observed in this
      region. Between 10.5 and 11 weeks, as the posterior suture separated,
      opacification appeared around the separated sutural area and rapidly developed
      into a mature cataract. The mechanism of cataract formation in the SCR rat lens
      may be associated with the continuous occurrence of a small proportion of poorly
      differentiated epithelial cells at the bow area and sutural dysplasia of the
      anterior lens fibres.

PMID- 8282044
TI  - Dose rate effect of 125I irradiation on normal rabbit eyes and experimental
      choroidal melanoma.
AB  - The dose rate effect of radiation by 125I plaque on choroidal melanoma and normal
      intraocular tissue was studied. In the first part of the experiment, high
      activity plaques (HAP) and low activity plaques (LAP) were implanted on rabbit
      eyes with experimental Greene choroidal melanoma to deliver a total dose of
      10,000 cGy to the tumor apex. The mean dose rate calculated at 0.5 mm from the
      inner sclera in eight eyes with high activity plaques was 3341.5 cGy hr-1 (1 cGy
      = 1 rad) while that in ten eyes with low activity plaques was 239.9 cGy hr-1. For
      tumors less than 1.0 mm in height, both groups showed complete tumor regression
      at the tumor implantation site after plaque treatment. For tumors more than 1.0
      mm in height, two out of two eyes in the low activity plaque group and one of
      four eyes in the high activity plaque group failed to show complete tumor
      regression. Both LAP and HAP were effective in eradicating tumors, but logistic
      regression analysis demonstrates that HAP was more effective than LAP when
      adjustment was made for initial tumor height (P = 0.032). Nine tumor control eyes
      without 125I plaque implantation demonstrated marked tumor growth within 3 weeks.
      In the second part of the experiment, 125I plaques were implanted on the sclera
      of 12 normal rabbits' eyes. Six received high dose rate plaque treatment, while
      the other six received low dose rate plaque treatment. Clinical and histologic
      examinations demonstrated more damaging effects to the normal chorioretinal
      tissues at the plaque implantation site in the high dose rate plaque group at 24
      weeks of follow-up. These results suggest that high dose rate plaques are more
      effective than low dose rate plaques when tumor height is statistically
      controlled. However, high dose rate delivery increases the damaging effects on
      normal intraocular tissue.

PMID- 8282045
TI  - Lens development in a dominant X-linked congenital cataract of the mouse.
AB  - Xcat is a recently identified mouse mutation causing X-linked dominant congenital
      cataract. The mutation is of particular interest as a possible animal model for
      the human X-linked cataract syndrome. Using light microscopy, we examined the
      histological changes of mutant lenses at selected intervals between embryonic (E)
      day 14 and postnatal (P) day 21. At E14, primary fiber formation completely fills
      the former lens vesicle in both normal and mutant mice, but in affected animals
      the primary fibers are irregularly arranged and show small foci of cellular
      disintegration. Progressive degeneration of primary fibers occurs from E15 to E18
      and, during late gestation, secondary lens fibers also begin to degenerate. The
      lens epithelium and newly differentiated fibers, however, show no evident
      abnormality. Postnatally, most of the lens substance becomes amorphous; the
      cataractous process terminates in rupture of the posterior lens capsule by P21.
      Analysis of crystallin and cytoskeletal proteins of postnatal cataractous lenses
      revealed no significant abnormalities when compared to normal lenses. The
      observed sequence of histological changes indicates that the Xcat mutation
      affects the differentiation of lens fiber cells at some point after their initial
      elongation.

PMID- 8282046
TI  - Endothelin 1 is a growth factor for corneal endothelium.
AB  - Endothelin 1 (ET1) is a newly discovered peptide found in various tissues, which
      exerts its biological effects through autocrine or paracrine pathways. Its
      presence and binding sites in the anterior chamber of the eye have recently been
      reported. Using a binding assay, we found the presence of a single class of
      receptors for ET1 on bovine corneal endothelial cells, whereas no ET1 could be
      detected in their conditioned medium. ET1 receptors appeared to be involved in
      BCE cell proliferation and migration. Furthermore, ET1 effects were additive to
      that of basic Fibroblast Growth Factor. Thus, we have shown for the first time
      that ET1 acts as a growth factor on corneal endothelium through a paracrine
      mediated action. This research suggests that ET1 has a role in corneal
      endothelium physiology and might provide a new field of investigation in the
      pharmacology of corneal endothelial healing.

PMID- 8282047
TI  - Suppression of S-antigen-induced experimental autoimmune uveoretinitis in Lewis
      rats by oral administration with CGS-13080, a thromboxane synthetase inhibitor.
AB  - Oral administration of CGS-13080 [imidazo (1, 5-alpha) pyridine-5-hexanoic acid],
      a thromboxane synthetase inhibitor, has been reported to cause a marked reduction
      in serum thromboxane B2 concentration in humans and animals. Since thromboxane
      metabolites play an important role in ocular inflammation, the effect of oral CGS
      13080 in the development of experimental autoimmune uveoretinitis in Lewis rats
      has been investigated. Females were immunized with bovine S-antigen (S-Ag).
      Treatment was started on day 0 of immunization. Animals were divided into three
      groups. The control group was fed a standard pellet diet, while the treated
      groups were fed the standard diet supplemented with either a low dose (0.8 g per
      10 kg pellet) or a high dose (1.6 g per 10 kg pellet) of CGS 13080. From day 10
      after immunization, the eyes of these rats were examined daily for clinical
      evidence of experimental autoimmune uveoretinitis. On day 14, the eyes were
      collected for histologic study. The cellular immune responses were evaluated on
      the draining inguinal lymph nodes. Blood samples were also collected for the
      measurement of anti-S-Ag antibody production, thromboxane B2 and prostaglandin A2
      levels. Clinical disease developed in 73.3% of the control rat group, 30.0% of
      the low-dose treated group and 17.6% of the high-dose group. The average
      histologic grade was 1.9 in the control group, 0.65 in low-dose group and 0.32 in
      high-dose group. Lymphocyte proliferation to S-Ag paralleled the clinical disease
      scores. Average stimulation indices were 10.9 in the controls, 7.5 in the low
      dose group and 2.2 in the high-dose group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282048
TI  - Regulation of fibronectin and laminin synthesis by retinal capillary endothelial
      cells and pericytes in vitro.
AB  - Retinal capillaries are composed of endothelial cells resting on a basement
      membrane, in which are embedded pericytes. In diabetes mellitus, the basement
      membrane becomes thickened, and there is a loss of pericytes. The relative
      contributions of endothelial cells and pericytes to the synthesis of
      extracellular matrix proteins which are components of the basement membrane are
      not well-characterized. To determine how a selective loss of pericytes might
      affect the composition of retinal capillary basement membranes, we used primary
      cultures of bovine retinal capillary endothelial cells and pericytes to determine
      the forms and quantify the amounts of laminin and fibronectin synthesized and
      secreted by these cell types as well as to determine how high glucose
      concentrations alter these parameters. Results of ELISAs showed that pericyte
      cell/matrix layers contained nearly ten times more fibronectin than endothelial
      cells (288 +/- 24 vs. 34 +/- 5 ng micrograms-1 DNA, P < 0.001), but the amounts
      of laminin were similar. D-glucose (40 mM) tripled the amount of fibronectin
      incorporated into the endothelial cell/matrix layer (102 +/- 4 vs. 34 +/- 5 ng
      micrograms-1 DNA, P < 0.05), but had a lesser effect on pericytes. The non
      metabolizable analogue L-glucose, also increased the amount of fibronectin
      incorporated in both pericyte and endothelial cell/matrix layers. The effects of
      D- and L-glucose on fibronectin secreted into the medium by both cell types were
      similar to the effects on incorporation of fibronectin into cell/matrix layers.
      Glucose had no effect on laminin synthesis. [35S]methionine radiolabeling and
      immunoprecipitation showed that pericytes and endothelial cells synthesize
      different forms of fibronectin. Both pericytes and endothelial cells synthesized
      an A and two B chains of laminin which were of similar apparent size, but the two
      cell types post-translationally modified the subunits differently. We conclude
      that pericytes and endothelial cells may contribute different forms and amounts
      of fibronectin and laminin to the retinal capillary basement membrane, so the
      preferential loss of pericytes in diabetes could result in basement membrane
      abnormalities which might lead to endothelial cell dysfunction.

PMID- 8282049
TI  - Decrease in glycation of lens proteins by lysine and glycine by scavenging of
      glucose and possible mitigation of cataractogenesis.
AB  - The amino acid lysine has been reported to delay cataractogenesis by 'some
      unknown mechanism'. Lysine and glycine were found to react with glucose at
      physiological pH and temperature and undergo non-enzymic glycation. The formation
      of glycated lysine was shown by paper and thin-layer chromatography, HPLC and
      using an authentic sample of epsilon-fructosyl lysine. Confirmation was made by
      studies on incorporation of U-[14C]glucose into lysine and glycine. The extent of
      glycation of lysine was 15.5% in 96 hr and rose to 20% in 20 days. Lysine and
      glycine alone of varying concentrations lowered the extent of glycation of lens
      proteins significantly in glucose-treated homogenates of normal lens from humans
      and goats. Scavenging of intracellular glucose and thereby protecting the lens
      proteins from excessive glycation appears to be the mechanism of action by which
      lysine and glycine could exercise beneficial effect on cataract.

PMID- 8282050
TI  - In vitro alteration of human lens curvatures by radial stretching.
AB  - The shapes of two human lenses of different ages (27 and 46 years old) were
      altered by applying a stretching force to the ciliary muscle. The force was in
      the outward radial direction and was produced by an electronically driven
      stretching instrument which is described. The lenses were photographed for
      different degrees of stretch, and their anterior and posterior curvatures
      analysed. All curves could be fitted to second order polynomial functions. The
      posterior curvatures did not appear to alter with stretch and were almost
      identical in both lenses. Although the anterior surfaces of both lenses changed
      with application of the stretching force, that of the younger lens showed a
      considerably greater alteration. Most changes in sagittal thickness occurred with
      radial stretching of up to 1.0 mm. The results of this work are compared to those
      of other studies on both functional and in vitro lenses.

PMID- 8282051
TI  - Retinal degeneration in motor neuron degeneration (mnd) mutant mice.

PMID- 8282052
TI  - Procedures for processing the rabbit primary vitreous for studies with
      transmission and scanning electron microscopy.

PMID- 8282053
TI  - Influence of hematopoietic growth factor on leukemic cells.

PMID- 8282054
TI  - Different mechanisms of inhibition by alkyl-lysophospholipid and phorbol ester of
      granulocyte-macrophage colony-stimulating factor binding to human leukemic cell
      lines.
AB  - We investigated the effects of rac-1-O-octadecyl-2-O-methyl-glycero-3
      phosphocholine (ET-18-OCH3) and 12-O-tetradecanoylphorbol-13-acetate (TPA) on
      granulocyte-macrophage colony-stimulating factor (GM-CSF) binding to human
      leukemic cell lines HL60, U937, KG-1, KG-1a, and K562. HL60, U937, and KG-1
      exhibited the high-affinity receptors, but KG-1a and K562 revealed no
      demonstrable receptors. ET-18-OCH3 inhibited GM-CSF binding to HL60, U937, and KG
      1 cells with a half-maximal inhibitory concentration of 16, 10, and 78 microM,
      respectively. ET-18-OCH3 at 10 microM reduced GM-CSF binding sites on HL60, U937,
      and KG-1, but had little effect on the dissociation constant (Kd). ET-18-OCH3 at
      10 and 30 microM significantly (p < 0.01) decreased, in a dose-dependent manner,
      the total uptake, surface binding, and internalization of GM-CSF. The
      internalization of GM-CSF was more profoundly inhibited than its surface binding.
      TPA at 1 and 10 nM inhibited GM-CSF binding. Inhibition of GM-CSF binding by a
      combination of ET-18-OCH3 (10 microM) and TPA (1 or 10 nM) was less than
      additive, and ET-18-OCH3 partially inhibited TPA-induced protein kinase C (PKC)
      depletion in the cytosol and translocation to the particulate fractions. It is
      suggested that the inhibition of GM-CSF binding by ET-18-OCH3 is due in part to
      disruption of the plasma membrane and that the inhibition of GM-CSF binding by
      TPA is due to activation of PKC.

PMID- 8282055
TI  - In vitro differentiation of B cells and myeloid cells from the early mouse embryo
      and its extraembryonic yolk sac.
AB  - The yolk sac is the first site of hematopoiesis during ontogeny. However, the
      source of early embryonic hematopoietic stem cells remains unresolved. Early
      studies have shown that cells obtained from day-8 and -9 extraembryonic yolk sacs
      can give rise to T cells and myeloid cells, whereas the embryo itself appears to
      lack such cells. Controversy remains as to whether it is the embryo itself or the
      extraembryonic yolk sac that contains the initial precursors capable of
      differentiating into B cells. This study used the approach of enriching
      hematopoietic stem cells by immunocytoadherence and studying cells isolated from
      within the embryo itself or from the yolk sac obtained at days 8 and 9 of mouse
      embryonic development. We report that on day 9, both yolk sac-derived and embryo
      derived cells can give rise to B cells and myeloid cells in vitro. On day 8,
      however, cells isolated from the yolk sac but not from the embryo produce myeloid
      colonies in vitro; neither source of stem cells generates B cells. Our study
      suggests that myeloid precursors migrate from yolk sac to embryo earlier than has
      previously been reported but that the origin for B cell precursors remains to be
      determined.

PMID- 8282056
TI  - Is hematopoiesis or its regulatory microenvironment the rate-limiting factor for
      LD50/30?

PMID- 8282057
TI  - Membrane electrical properties associated with insulin receptor downregulation in
      human erythrocytes.
AB  - This study investigated the alterations in the electrical properties of human
      erythrocytes that occur during the insulin-induced internalization of insulin
      receptors (downregulation). Using a dielectric relaxation technique based on the
      Maxwell-Wagner effect, the data indicate a steady decrease over time in membrane
      conductivity, membrane permittivity, and conductivity of the cytosol in
      erythrocytes that have been stimulated to undergo downregulation by the addition
      of insulin. We hypothesize that variations in active transport properties as well
      as changes in membrane lipids and/or proteins occur during the process of insulin
      induced downregulation of insulin receptors.

PMID- 8282058
TI  - Mutated genes in myeloid leukemias.

PMID- 8282059
TI  - Modulation of human myelopoiesis by human gangliosides.
AB  - Cell surface gangliosides are potent modulators of cellular proliferation. We
      hypothesize that gangliosides shed by tumor cells modulate hematopoiesis and
      contribute to human tumor-associated suppression of hematopoiesis. To test this
      hypothesis, we determined the effects on myeloid colony formation by human bone
      marrow mononuclear cells of total gangliosides isolated from human brain and of
      seven highly purified individual ganglioside species (GM1, GM2, GD1a, GD1b, GD2,
      GD3, and GT1b). Total human brain gangliosides and certain individual species,
      GD1a, GD1b, and GT1b, significantly inhibited myeloid colony formation (number as
      well as size). The most complex molecules, GD1a, GD1b, and GT1b, were the most
      inhibitory, suggesting that the degree of inhibition is related to ganglioside
      structural complexity. To extend these findings, we also investigated certain
      tumor-derived (neuroblastoma) gangliosides, which we found inhibited both myeloid
      colony formation and 3H-thymidine incorporation by human bone marrow mononuclear
      cells. These data suggest a role for gangliosides, which are shed by
      proliferating cells, in the regulation of human hematopoiesis and may explain the
      bone marrow hypoplasia observed in association with many human malignancies.

PMID- 8282060
TI  - Acute toxic effects of 3'-azido-3'-deoxythymidine (AZT) on normal and
      regenerating murine hematopoiesis.
AB  - The immediate hematopoietic response to 3'-azido-3'-deoxythymidine (AZT) was
      characterized in an unperturbed and regenerating mouse marrow model to identify
      the in vivo hematopoietic targets of AZT and test whether AZT toxicity is
      dependent on the proliferative activity of the hematopoietic targets. B6D2F1 mice
      received intravenous (IV) bolus injections of 30, 60, 120, and 240 mg/kg AZT.
      None of the doses induced consistent changes in the number of hematopoietic stem
      and progenitor cells. However, identical cumulative doses administered as an
      intravenous 24-hour infusion led to marked changes. Spleen colony-forming units
      (CFU-S) per femur were diminished to about 60%. Burst-forming units-erythroid
      (BFU-E) and colony-forming units-erythroid (CFU-E) were substantially reduced to
      about 15 to 35% at the two highest doses, whereas the femoral content of colony
      forming units-granulocyte/macrophage (CFU-GM) and colony-forming units
      megakaryocyte (CFU-Meg) was unchanged. When administered to mice whose marrow was
      regenerating from total-body irradiation (TBI) and subsequent bone marrow
      transplantation (high proliferative fraction), 240 mg/kg AZT caused considerable
      reductions of all hematopoietic cell stages even when given as a single IV
      injection. The results indicate that (1) the mode of application is critical for
      AZT hematotoxicity; (2) erythropoietic progenitors are the most sensitive to AZT
      toxicity; and (3) hematotoxicity increases with increasing proliferative
      activity.

PMID- 8282061
TI  - Relative roles of osteoclast colony-stimulating factor and macrophage colony
      stimulating factor in the course of osteoclast development.
AB  - Although recent studies have shown that osteopetrotic (op/op) mice lack
      macrophage colony-stimulating factor (M-CSF or CSF-1), the precise role of M-CSF
      in the development of immature osteoclasts remains unknown. Using a recently
      discovered osteoclast-specific colony-stimulating factor (O-CSF) and in vitro
      long-term bone marrow culture systems, we investigated the ability of op/op and
      control marrow stromal cells to support the production of O-CSF-responsive
      clonogenic osteoclast progenitors (colony-forming unit-osteoclast [CFU-O]) from
      inoculated normal stem cells. Remarkably, op/op stromal cell cultures produced
      five times as many nonadherent cells as control cultures throughout the
      experimental period of 14 weeks; an average of 37% of these cells were nonviable
      compared with 8% in control cultures. Significantly higher numbers of CFU-O were
      found in op/op cultures than in control cultures; the CFU-O in op/op and control
      cultures were proliferating at a similar rate. Higher numbers of calcitonin
      receptor-bearing cells were found when harvested cells from op/op flasks were
      cultured with 1,25(OH)2D3. These studies clearly show that op/op marrow stromal
      cells can support the differentiation and proliferation of osteoclast progenitors
      from inoculated stem cells and provide the first experimental evidence that M-CSF
      is not essential for the early stages of osteoclast development. We hypothesize
      that while O-CSF supports proliferation of osteoclast progenitors, M-CSF plays a
      role in the later development and maturation of the progenitor as well as in the
      prevention of cell death.

PMID- 8282062
TI  - Embryonic origin of hematopoietic stem cells.

PMID- 8282063
TI  - Interleukin-4 mRNA and protein in activated human T cells are enhanced by
      interleukin-7.
AB  - We studied the effect of the stroma-derived cytokine interleukin-7 (IL-7) on the
      expression of IL-4 in human T cells at mRNA and protein level. The results
      demonstrate that IL-7 did not induce IL-4 mRNA in resting T cells. However,
      concanavalin A (con A)-induced IL-4 mRNA expression was enhanced by costimulation
      with con A plus IL-7. Nuclear run-on analysis revealed that IL-7 did not affect
      the transcription rate of the IL-4 gene. The half-life of con A-induced IL-4
      transcripts, however, was increased upon con A plus IL-7 treatment, indicating
      that the effect of IL-7 is mediated at posttranscriptional level. In accordance
      with the mRNA results, IL-4 protein was not detected in supernatants of
      unstimulated T cells or T cells exposed to IL-7. In contrast, IL-7 augmented the
      con A-induced secretion of IL-4 protein significantly. In addition, it was
      noticed that anti-IL-1 beta and anti-tumor necrosis factor-alpha (anti-TNF-alpha)
      did not abolish the effect of IL-7 on the con A-induced IL-4 secretion,
      indicating that the IL-7 effect is not mediated by the release of these
      cytokines. These results indicate that a stroma-derived factor can affect IL-4
      expression in activated human T cells.

PMID- 8282064
TI  - Retroviral-mediated gene transfer of a mutant H-ras gene into normal human bone
      marrow alters myeloid cell proliferation and differentiation.
AB  - To investigate the effects of mutant ras expression on the growth and
      differentiation of normal human bone marrow, we used retrovirus-mediated gene
      transfer. A retrovirus (HR-1) containing a mutant ras gene (H12-ras) in addition
      to the selectable neo gene was transferred by cocultivation of a packaging cell
      line with long-term cultures of normal human bone marrow. Controls were
      established by cocultivating aliquots of the same bone marrow with a retrovirus
      (VSN-2) containing only neo. The efficiency of gene transfer, as determined by
      the percentage of G418-resistant colony-forming units-granulocyte/macrophage (CFU
      GM) immediately after termination of cocultivation, was similar: 8 +/- 4% with HR
      1 and 5 +/- 3% with VSN-2. After a further week in long-term culture, there was
      an increase in the number and percentage of G418-resistant CFU-GM in both the HR
      1-infected and VSN-2-infected marrows. Thereafter, the numbers of G418-resistant
      CFU-GM declined, becoming undetectable at 4 weeks. The time course of the
      production of G418-resistant colonies was not significantly different in HR-1-
      and VSN-2-infected marrows, indicating that H12-ras did not alter the
      proliferation of normal CFU-GM. However, the total cellularity of HR-1-infected
      marrow cultures was significantly greater than that of VSN-2-infected marrow
      cultures. This was due to increased cellular proliferation of HR-1-infected
      cultured cells, since differential counts showed a significant increase in
      myeloid blast cells together with a slight reduction in mature myeloid cells in
      HR-1-infected marrow compared to baseline and to VSN-2-infected marrow. No
      leukemic blast cell colonies were grown from HR-1-infected marrows or control
      marrows, and HR-1 infection did not confer serum independence. These data show
      successful retroviral infection of normal bone marrow progenitor cells and
      suggest that expression of mutant H12-ras in such cells results in enhanced
      proliferation of early myeloid cells at the expense of differentiation.

PMID- 8282065
TI  - Regulation of interleukin-1 and tumor necrosis factor-alpha induced granulocyte
      macrophage colony-stimulating factor gene expression: potential involvement of
      arachidonic acid metabolism.
AB  - Signal transduction pathways evoked by interleukin-1 (IL-1) and tumor necrosis
      factor-alpha (TNF-alpha) to stimulate expression of other cytokines in
      mesenchymal cells are not clearly understood. Stimulation of the murine bone
      marrow stromal cell line +/(+)-1.LDA 11 with IL-1 (500 U/ml) in combination with
      TNF-alpha (500 U/ml) (IL-1 plus TNF-alpha) induced expression of c-jun mRNA as
      well as granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA. We
      investigated the possibility that arachidonic acid metabolites, acting through
      protein kinase C (PKC) and perhaps also through the PKC-responsive transcription
      factor c-jun/AP-1, may be responsible for regulating GM-CSF transcription in
      these stromal cells. Expression of GM-CSF mRNA was preceded by IL-1 plus TNF
      alpha induced arachidonate release (assayed using the 3H-derivative).
      Pretreatment of cells with the phospholipase A2 inhibitor quinacrine (20 microM)
      inhibited accumulation of both c-jun and GM-CSF mRNA but had no influence on
      expression of other genes induced by IL-1 and TNF-alpha, including leukemia
      inhibitory factor (LIF). In addition, quinacrine partially blocked IL-1 plus TNF
      alpha induced 3H-arachidonic acid release from prelabeled stromal cells.
      Furthermore, exogenous arachidonate (10 to 50 microM) induced expression of c
      jun. To investigate the role of arachidonate in GM-CSF transcription, we used a
      reporter vector consisting of the murine GM-CSF promoter linked to firefly
      luciferase. Transfection efficiency was monitored by assessing expression of a
      constitutively active gene, RSV-beta galactosidase. In this system, quinacrine
      significantly inhibited IL-1 plus TNF-alpha induced GM-CSF transcription assayed
      with the reporter construct. Exogenous arachidonic acid alone (10 microM)
      increased activity of GM-CSF reporter vector 1.5-fold over control. These results
      are consistent with the hypothesis that arachidonate metabolites are involved in
      the signaling pathway that leads to IL-1 plus TNF-alpha induced GM-CSF gene
      expression. Thus, transcriptional activation of GM-CSF gene is mediated, in part,
      by the arachidonate cascade.

PMID- 8282066
TI  - Retroviral transduction of Philadelphia-positive chronic myeloid leukemia cells
      with a human mutant p53 cDNA and its effect on in vitro proliferation.
AB  - Alterations in the tumor suppressor gene p53 are associated with the pathogenesis
      of blastic transformation of chronic myeloid leukemia (CML), but their exact
      role, particularly their relationship with the chimeric protein p210BCR/ABL, is
      poorly defined. Point mutations in p53 have been found in some cases of blast
      crisis and CML blastic cell lines, but it is not clear whether complete
      inactivation of p53 tumor suppressor function, with or without the production of
      a mutant protein, can by itself trigger the process of blastic transformation. By
      using retroviral gene transfer, we showed that the introduction of a mutant human
      p53 cDNA into hematopoietic progenitor cells from patients with CML in chronic
      phase, which already contain p210BCR/ABL, could promote their proliferation in
      vitro, and occasionally even lead to the growth of factor-independent colonies.
      We conclude that a mutant p53 may act in synergy with p210BCR/ABL and promote the
      survival and proliferation of CML hematopoietic stem and progenitor cells in
      vitro.

PMID- 8282067
TI  - Can neurotrophic factors prevent or reverse motoneuron injury in amyotrophic
      lateral sclerosis?

PMID- 8282068
TI  - The therapeutic potential of neurotrophic factors in the treatment of Parkinson's
      disease.
AB  - Partial symptomatic relief from Parkinson's disease with levodopa has proven to
      be one of the rare success stories in the development of drugs to combat
      neurodegenerative diseases. However, no therapeutic agent has yet conclusively
      been shown to slow, halt, or reverse the underlying progression of neuronal loss
      in Parkinson's disease or any other human neurodegenerative disorder. This
      article reviews recent developments in the biology of neurotrophic growth
      factors, especially members of the nerve growth factor-related neurotrophin
      family, which may point to their potential as therapeutic agents for the
      treatment of Parkinson's disease. Parkinson's disease, characterized by the
      progressive loss of dopaminergic neurons of the substantia nigra, is one of the
      most well-characterized neurodegenerative disorders from both an anatomical and
      biochemical standpoint, but as yet the etiology of this disease remains poorly
      understood. Epidemiological, neurochemical, and pathological studies have
      provided a wealth of data that have spawned many theories of the underlying cause
      of Parkinson's disease, including environmental and genetic origins. Future
      elucidation of the disease process in Parkinson's disease may yield obvious
      therapeutic strategies, but even in the absence of such knowledge there are
      several general approaches that can be taken as strategies for the treatment of a
      "focal" neurodegenerative disease. These include: (a) mimetics, activation of the
      postsynaptic target(s) of the missing neurons through mimetics of the missing
      neurotransmitter, e.g., use of a dopamine precursor or dopamine receptor agonist
      in Parkinson's disease; (b) transplants, replenishment of the missing neurons via
      transplantation of neurons or nonneuronal cells secreting the appropriate
      neurotransmitter, e.g., fetal nigral grafts in Parkinson's disease; (c)
      neurotrophic factors or neuroprotectants, intervention with neurotrophic
      factors/neuroprotective agents which slow, halt, or reverse the progression of
      neuronal degeneration, e.g., a dopamine neurotrophic factor in Parkinson's
      disease. The scope of the present article is limited to a review of recent
      progress in the biology of neurotrophic factors that relates to their potential
      clinical use in treating the loss of dopamine neurons in Parkinson's disease.

PMID- 8282069
TI  - Expression of neurotrophins by midbrain dopaminergic neurons.

PMID- 8282070
TI  - Can graft-derived neurotrophic activity be used to direct axonal outgrowth of
      grafted dopamine neurons for circuit reconstruction in primates?

PMID- 8282071
TI  - Trophism, transplantation, and animal models of Parkinson's disease.

PMID- 8282072
TI  - Seizure-induced changes in neurotrophin expression: implications for epilepsy.

PMID- 8282073
TI  - Nerve growth factor pharmacology: application to the treatment of cholinergic
      neurodegeneration in Alzheimer's disease.
AB  - The proposal that NGF or compounds that induce the expression of endogenous NGF
      may be useful in the treatment of AD is based upon a wealth of evidence showing
      that NGF effectively attenuates lesion-induced cholinergic deficits and cognitive
      impairments in animal models. In addition, a recent clinical study with chronic
      NGF treatment in an AD patient showed promise. Olson et al. showed that NGF
      treatment increased blood flow, [11C]nicotine uptake, and 11C binding in the
      cerebral cortex. In addition, NGF infusions normalized EEG patterns and improved
      performance in word recognition tests. Further clinical trials with either NGF or
      NGF-enhancing compounds will allow determination of whether the animal-based
      study approach to designing clinically relevant drugs will be advantageous to the
      treatment of AD. Further findings on the effectiveness of NGF in AD patients are
      reported by Lars Olson (this volume).

PMID- 8282074
TI  - Experimental evidence for growth factor treatment and function in certain
      neurological disorders.
AB  - This issue focuses on the potential utilization or involvement of growth factors
      in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and
      epilepsy. Certainly, the role of growth factors in other neurological disorders
      associated with stroke, trauma, and neurodegeneration needs to be considered.
      While there is no direct evidence to indicate that a neurological disorder is
      associated with the compromised function of a specific growth factor, the use of
      these molecules as therapeutic agents is justifiable. Undoubtedly, the outcome of
      current clinical trials will certainly influence future decisions on the use of
      growth factor therapies.

PMID- 8282075
TI  - Delivery of trophic factors to the primate brain.

PMID- 8282076
TI  - Strategies for modulating Trk receptor activity.

PMID- 8282077
TI  - The potential for treating neurodegenerative disorders with NGF-inducing
      compounds.

PMID- 8282078
TI  - Site-specific pharmacology for the treatment of Alzheimer's disease.

PMID- 8282079
TI  - Trophic support of motoneurons: physiological, pathophysiological, and
      therapeutic implications.

PMID- 8282080
TI  - NGF and the treatment of Alzheimer's disease.
AB  - Issues related to the possible treatment of Alzheimer's disease with nerve growth
      factor (NGF) are discussed. Animal research has demonstrated that the ascending
      cholinergic projections in the brain express low- and high-affinity receptors for
      NGF and are NGF-sensitive as well as probably NGF-dependent. Cholinergic lesions
      lead to cognitive disturbances, and treatment with NGF can improve cognitive
      behavior in animals. It thus seems reasonable to attempt to counteract the
      degeneration of cholinergic systems known to occur in patients with Alzheimer's
      disease by treatment with NGF. There are several different possible ways of
      stimulating NGF receptors such as NGF infusion, implantation of slow-release
      biodegradable pellets, using carrier-mediated transport across the blood-brain
      barrier, grafting NGF-producing cells, transferring genes directly to the brain,
      developing NGF receptor agonists, or controlling the endogenous NGF production.
      The first clinical trial of NGF infusion is described in some detail. Based on
      background information from intracerebral infusion of NGF in parkinsonian
      patients, attempting to support intraputaminal chromaffin tissue grafts, a study
      was initiated using a radio-controlled fully implantable pumping device
      delivering NGF to the lateral ventricle. Several transient or more long-lasting
      "improvements" were noted in the pilot case. These involved increases of blood
      flow and nicotine binding as evaluated by positron-emission tomography as well as
      improvement of the EEG and certain psychological tests, tapping verbal episodic
      memory. Negative effects of NGF or formation of antibodies against NGF were not
      noted. In discussing the pilot case, the one conclusion which appears warranted
      is that it is reasonable to continue the clinical research with NGF treatment of
      a low number of patients with Alzheimer's disease. The question of whether
      neurotrophin-mediated mechanisms are disturbed in Alzheimer's disease is
      discussed. While this issue cannot be settled at present, it is argued that NGF
      can be used as a pharmacological agent, whether or not there are any primary
      disturbances of neurotrophin-mediated mechanisms in Alzheimer's disease. Finally,
      the possibility that NGF might have other positive or negative effects is
      discussed. In particular, the increase in blood flow noted in the Alzheimer
      patient suggests that data from clinical research may also generate a feedback to
      basic science, thus aiding in attempts to find new treatment strategies for
      neurodegenerative diseases.

PMID- 8282081
TI  - Neurotrophic factors in the treatment of motor neuron disease and trauma.

PMID- 8282082
TI  - The use of trophic factors in degenerative motoneuron diseases.

PMID- 8282083
TI  - Experimental rationale for the therapeutic use of neurotrophins in amyotrophic
      lateral sclerosis.
AB  - Current therapeutic efforts to treat chronic and progressive neurodegenerative
      disease include, for the first time, attempts to regenerate affected nervous
      tissue using neurotrophic factors. The rationale for using trophic factors
      includes the understanding that they support neuronal survival and regrowth
      processes. The potential benefits of trophic factor therapy will be no more
      realized in the near future than in the treatment of amyotrophic lateral
      sclerosis (ALS). ALS is pathologically characterized by the selective
      degeneration of specific populations of cranial and spinal motoneurons. Evidence
      for the existence of factors that support motoneurons has come from studies
      demonstrating that motoneurons receive trophic influences from various tissues,
      both central and peripheral, within their local environment. Although the
      identity of these putative tissue-derived factors has remained enigmatic, recent
      studies have demonstrated that several previously characterized trophic factors
      exhibit trophic influences on motoneurons. Among these are several members of the
      neurotrophin family, most notably brain-derived neurotrophic factor. These
      neurotrophins meet most of the criteria to be considered motoneuron trophic
      factors: they are locally available to motoneurons in vivo; motoneurons express
      specific receptors for these factors; and exogenous application of these factors
      mimicks the effects of the uncharacterized endogenous agents. The clinical use of
      these factors for the treatment of ALS, therefore, appears to be scientifically
      justified.

PMID- 8282084
TI  - Insulin-like growth factor-I: potential for treatment of motor neuronal
      disorders.
AB  - Motor neuronal disorders, such as the loss of spinal cord motor neurons in
      amyotrophic lateral sclerosis or the degeneration of spinal cord motor neuron
      axons in certain peripheral neuropathies, present a unique opportunity for
      therapeutic intervention with neurotrophic proteins. Normally, such proteins do
      not cross the blood-brain barrier, but spinal cord motor neuron axons and nerve
      terminals lie outside the barrier and thus may be targeted by systemic
      administration of protein growth factors. Insulin-like growth factor-I (IGF-I)
      receptors are present in the spinal cord, and, like members of the neurotrophin
      receptor family, IGF-I receptors mediate signal transduction via a tyrosine
      kinase domain. IGF-I was found to prevent the loss of choline acetyltransferase
      activity in embryonic spinal cord cultures, as well as to reduce the programmed
      cell death of motor neurons in vivo during normal development or following
      axotomy or spinal transection. Consistent with earlier reports that IGF-I
      enhances motor neuronal sprouting in vivo, subcutaneous administration of IGF-I
      increases muscle endplate size in rats. Subcutaneous injections of IGF-I also
      accelerate functional recovery following sciatic nerve crush in mice, as well as
      attenuate the peripheral motor neuropathy induced by chronic administration of
      the cancer chemotherapeutic agent vincristine in mice. Doses of IGF-I that
      accelerate recovery from sciatic nerve crush in mice result in elevated serum
      levels of IGF-I which are similar to those obtained following subcutaneous
      injections of formulated recombinant human IGF-I (Myotrophin) in normal human
      subjects. Based on these findings, together with evidence of safety in animals
      and man, clinical trials of recombinant human IGF-I have been initiated in
      patients with amyotrophic lateral sclerosis and are planned to begin soon in
      patients with chemotherapy-induced peripheral neuropathies.

PMID- 8282085
TI  - Mechanisms of neurotrophic factor protection against calcium- and free radical
      mediated excitotoxic injury: implications for treating neurodegenerative
      disorders.

PMID- 8282086
TI  - On the therapeutic potential for insulin-like growth factor use in motor neuron
      disease.

PMID- 8282087
TI  - The biology of macrophages: I. General principles and properties.

PMID- 8282088
TI  - Interleukin 4 inhibits the proliferation and promotes the maturation of human
      leukemic early B cells.
AB  - The effects of interleukin 4 (IL-4) on human leukemic precursor B-cell lines were
      investigated. Recombinant IL-4 (rIL-4) was added to three acute lymphoblastic
      leukemia-derived pre B-cell lines: Reh, Km3 and Nalm-6. Our results show that rIL
      4 significantly decreases continuous proliferation of Reh and Km3 cells while
      Nalm-6 cells have a limited response in this respect. This rIL-4 effect is dose
      dependent and can be neutralized by anti-IL-4 monoclonal antibody (mAb).
      Furthermore, rIL-4 down-regulated IL-3-induced proliferation of Reh cells.
      Phenotypic analysis of rIL-4-treated cells points to significant induction of
      surface marker maturation of leukemic cells by this cytokine. Together, these in
      vitro data suggest that IL-4: 1) inhibits the proliferation and 2) promotes the
      differentiation of certain human leukemic B-cell precursors.

PMID- 8282089
TI  - Evidence that the extracellular N-terminal domain of C5aR contains amino-acid
      residues crucial for C5a binding.
AB  - The human C5a anaphylatoxin is a cationic 74 amino-acid long glycopeptide which
      derives from proteolysis of the fifth component of complement. It interacts with
      high affinity with a receptor that belongs to the G protein-coupled receptor
      superfamily. Several studies have previously suggested that multiple contact
      points between C5a and the receptor are required to achieve high-affinity
      interaction. However, at the receptor level little is known about the sites of
      interaction with C5a. We have investigated by in vitro mutagenesis whether the N
      terminal extracellular sequence of the C5a receptor, which is rich in aspartic
      acid residues, could play some role in C5a binding. Conversion of Asp10 into
      asparagine did not impair the level of expression at the plasma membrane, nor did
      it alter the affinity for C5a. However, we consistently observed a discrepancy
      between an apparent high level of surface expression and a weak capacity to bind
      C5a with high affinity, suggesting that many receptor molecules, although present
      on the cell surface, might be misfolded and unable to bind C5a. Replacement of
      Pro9 by an isoleucine had little effect, if any, on either the affinity or the
      C5a-binding capacity, whereas the conversion of Pro36 into leucine dramatically
      reduced the expression of high-affinity receptor at the cell surface. N
      glycosylation of human C5a receptor was found to be dispensable for the function
      of the receptor.

PMID- 8282090
TI  - Cytoskeletal regulation of chemotactic receptors: molecular complexation of N
      formyl peptide receptors with G proteins and actin.
AB  - Signal transduction via receptors for N-formylmethionyl peptide chemoattractants
      (FPR) on human neutrophils is a highly regulated process. It involves direct
      interaction of receptors with heterotrimeric G-proteins and may be under the
      control of cytoskeletal elements. Evidence exists suggesting that the
      cytoskeleton and/or the membrane skeleton determines the distribution of FPR in
      the plane of the plasma membrane, thus controlling FPR accessibility to different
      proteins in functionally distinct membrane domains. In desensitized cells, FPR
      are restricted to domains which are depleted of G proteins but enriched in
      cytoskeletal proteins such as actin and fodrin. Thus, the G protein signal
      transduction partners of FPR become inaccessible to the agonist-occupied
      receptor, preventing cell activation. We are investigating the molecular basis
      for the interaction of FPR with the membrane skeleton, and our results suggest
      that FPR, and possibly other receptors, may directly bind to cytoskeletal
      proteins such as actin.

PMID- 8282091
TI  - Phospholipases and activation of the NADPH oxidase.
AB  - The signal transductional mechanisms regulating the activation of NADPH oxidase,
      the respiratory burst enzyme in phagocytic cells, are not completely understood.
      Receptors for most physiologic stimuli trigger the activation of various
      phospholipases, including phospholipases A2, C, and D. The lipid mediators formed
      (arachidonic acid, 1,2-diacylglycerol, and phosphatidic acid) have been
      implicated as second messengers in the induction of the respiratory burst. In
      intact cells, we have correlated phospholipase D activation and the production of
      phosphatidic acid with the activation of NADPH oxidase, using the drug
      propranolol. Phosphatidic acid activated NADPH oxidase in a cell-free system, but
      the level of activation was low. 1,2-Diacylglycerol markedly enhanced NADPH
      oxidase activation by phosphatidic acid. The synergistic effect required the
      diacyl species, since mono- or tri-acylglycerols were ineffective. Phosphatidic
      acid could be replaced by either lysophosphatidic acid or phosphatidylserine, but
      not by phosphatidylcholine, phosphatidylethanolamine, or phosphatidylinositol,
      suggesting specificity for an anionic phospholipid. Since other cell-free
      activators of NADPH oxidase (arachidonic acid, sodium dodecyl sulfate) are also
      anionic amphiphiles, phosphatidic acid may directly interact with an enzyme
      component(s). The targets for phosphatidic acid and diacylglycerol in the cell
      free system are currently under investigation. These results emphasize the
      critical importance of phospholipases, particularly phospholipase D, in the
      regulation of the respiratory burst.

PMID- 8282092
TI  - Cytosolic oxidase factors in the NADPH-dependent oxidase of human neutrophils.
AB  - The NADPH-dependent superoxide generating system of human PMNs is a complex,
      multicomponent system. Studies over the past two decades have identified some of
      the various components both in the membrane and in the cytosol. The cytosolic
      factors p47 phox and p67 phox are clearly essential components of the oxidase, as
      evidenced by their absence producing autosomal CGD. Despite this, the specific
      function of each of these factors in the assembled oxidase remains unknown. In
      the case of p47 phox, determinants for translocation are multifactorial,
      depending in part on phosphorylation and in part on the participation of a
      functional domain at p47 phox(323-332). The importance of SH3 regions and proline
      rich domains in intramolecular interactions and associations with the membrane
      skeleton remain to be defined. In addition, factors which modulate the assembly
      of this oxidase are largely unknown and their elucidation may provide insights
      into novel means by which to modify the inflammatory response.

PMID- 8282093
TI  - Proton channels, plasma membrane potential, and respiratory burst in human
      neutrophils.
AB  - When confronted with invading microorganisms, neutrophils undergo a number of
      nearly synchronous reactions including the generation of microbicidal reactive
      oxygen intermediates by the NADPH oxidase. These reactions are accompanied by a
      slow depolarization, from resting values of-60 mV to levels probably exceeding 0
      mV. The depolarization is transient, indicating that a compensatory charge
      transport mechanism is activated. Activation of the oxidase system causes a
      massive burst of metabolic acid generation that would, if uncompensated, lower
      the intracellular pH of neutrophils by over 5 units, to lethal levels (pH = 2).
      Neutrophils must therefore possess particularly effective regulatory systems to
      avoid excessive cytosolic acidification. The recently described H+ conductance of
      neutrophils may counteract both the acidification and the depolarization.
      Activation of the H+ conductance occurs at depolarizing voltages and is promoted
      by cytosolic acidification, a combination that takes place during the respiratory
      burst. The NADPH oxidase of neutrophils is thus associated to an unusual,
      particularly efficient mechanism of H+ export and charge compensation. The
      sequential activation of these two systems causes neutrophils to depolarize
      through the activation of an electron transport chain, and to repolarize through
      the activation of a H+ conductance.

PMID- 8282094
TI  - Regulation of phagocyte function by low molecular weight GTP-binding proteins.
AB  - The mechanisms used by phagocytic leukocytes in the process of bacterial killing
      are regulated by GTP-binding proteins of the Ras superfamily. In particular, the
      formation of toxic oxygen metabolites via the NADPH oxidase requires the action
      of both Rac and Rap1A proteins. Rac2 forms a third cytosolic component of the
      human neutrophil NADPH oxidase. Rac2 is active in its GTP-bound form, and
      requires post-translational processing (isoprenylation) in order to interact with
      regulatory proteins which stimulate the exchange of GTP for GDP. In the resting
      neutrophil, Rac is localized to the cytosol in the form of a complex with a GDP
      dissociation inhibitor (GDI) protein. Upon cell activation, this complex is
      disrupted to enable Rac to translocate to the active oxidase at the plasma
      membrane. The Rac-GDI complex may be regulated by the release of specific lipids
      known to be generated during phagocyte activation.

PMID- 8282095
TI  - Granules and vesicles of human neutrophils. The role of endomembranes as source
      of plasma membrane proteins.

PMID- 8282096
TI  - Molecular cloning, functional expression and localization of an inward rectifier
      potassium channel in the mouse brain.
AB  - We have cloned an inward-rectifier potassium channel from a mouse brain cDNA
      library, studied its distribution in the brain by in situ hybridization and
      determined the chromosomal localization of the gene. A mouse brain cDNA library
      was screened using a fragment of the mouse macrophage IRK1 cDNA as a probe. Two
      duplicate clones of approximately 5.5 kb were obtained. Xenopus ococytes injected
      with cRNA derived from the clone expressed a potassium channel with inwardly
      rectifying channel characteristics. The amino acid sequence of the clone was
      identical to that of IRK1 recently cloned from a mouse macrophage cell line. In
      situ hybridization study showed the mouse brain IRK1 to be generally distributed
      throughout the brain, but in particular subsets of neurons at high levels. The
      gene was placed in the distal region of mouse chromosome 11, which contains
      several uncloned neurological mutations. These results provide the first
      demonstration of the cloning and distribution of an inward rectifier potassium
      channel from the nervous system.

PMID- 8282097
TI  - Dramatic changes in control properties that accompany channelling and metabolite
      sequestration.
AB  - A simple summation theorem describes the control of fluxes in 'ideal' metabolic
      pathways. This paper shows how this theorem and the control properties of a
      pathway change when direct transfer of intermediates and/or sequestration of
      metabolites involved in moiety conservations (by enzymes present at high
      concentrations) take place. The derived generalized summation theorem quantifies
      the extent to which metabolite sequestration decreases and direct metabolite
      transfer can increase the control exerted by enzymes on the flux. The
      implications of metabolite channelling for the control of fluxes are discussed
      quantitatively.

PMID- 8282098
TI  - Artificially glycosylated alpha-chymotrypsin in reversed micelles of Aerosol OT
      in octane. A new approach to elucidation of the role of carbohydrate moieties in
      glycoproteins.
AB  - A comparative study of native and artificially glycosylated alpha-chymotrypsin in
      reversed micelles of Aerosol OT in octane was carried out. D-Glucosamine and 1
      ethyl-3-(3-dimethylaminopropyl)carbodiimide were used as modifying agents to
      yield glycosylated enzyme. Unlike the native alpha-chymotrypsin, the modified
      protein tended to form reversible oligomeric structures, revealed by the
      appearance of an additional maximum (characteristic of dimeric forms of protein
      functioning) as a result of the enzyme catalytic activity being dependent on the
      AOT hydration degree. Dependence of the enzyme catalytic activity on the
      surfactant concentration in the case of the modified enzyme was similar to that
      of glycoproteins, and suggests its membrane affinity. The role of carbohydrate
      moieties in the functioning of glycoproteins is discussed.

PMID- 8282099
TI  - Flash-induced membrane potential generation by cytochrome c oxidase.
AB  - Flash-induced single-electron reduction of cytochrome c oxidase. Compound F
      (oxoferryl state) by RuII(2,2'-bipyridyl)3(2+) [Nilsson (1992) Proc. Natl. Acad.
      Sci. USA 89, 6497-6501] gives rise to three phases of membrane potential
      generation in proteoliposomes with tau values and contributions of ca. 45
      microsecond (20%), 1 ms (20%) and 5 ms (60%). The rapid phase is not sensitive to
      the binuclear centre ligands, such as cyanide or peroxide, and is assigned to
      vectorial electron transfer from CuA to heme a. The two slow phases kinetically
      match reoxidation of heme a, require added H2O2 or methyl peroxide for full
      development, and are completely inhibited by cyanide; evidently, they are
      associated with the reduction of Compound F to the Ox state by heme a. The charge
      transfer steps associated with the F to Ox conversion are likely to comprise (i)
      electrogenic uptake of a 'chemical' proton from the N phase required for
      protonation of the reduced oxygen atom and (ii) electrogenic H+ pumping across
      the membrane linked to the F to Ox transition. Assuming heme a 'electrical
      location' in the middle of the dielectric barrier, the ratio of the rapid to slow
      electrogenic phase amplitudes indicates that the F to Ox transition is linked to
      transmembrane translocation of 1.5 charges (protons) in addition to an
      electrogenic uptake of one 'chemical' proton required to form Fe(3+)-OH- from
      Fe4+ = O2-. The shortfall in the number of pumped protons and the biphasic
      kinetics of the millisecond part of the electric response matching biphasic
      reoxidation of heme a may indicate the presence of 2 forms of Compound F,
      reduction of only one of which being linked to full proton pumping.

PMID- 8282100
TI  - Structural study of rat thyroid transcription factor 1 homeodomain (TTF-1 HD) by
      nuclear magnetic resonance.
AB  - The 500 MHz 1H NMR spectrum of a 68-residue peptide, encompassing the rat thyroid
      transcription factor 1 homeodomain (TTF-1 HD), was fully assigned using standard
      2D NMR methodology. The secondary structure elements and their spatial
      organization were determined and led to a structure very similar to that
      previously described for other homeodomains and expected also for TTF-1 HD from
      homology modeling predictions. The three-dimensional arrangement of the three
      helix fragments of TTF-1 HD preserves the helix-turn-helix motif commonly
      occurring in many classes of DNA-binding proteins.

PMID- 8282101
TI  - Induction of cytoplasmic factors that bind to the 3' AU-rich region of human
      interferon beta mRNA during early development of Xenopus laevis.
AB  - Certain endogenous Xenopus mRNAs, carrying a destabilizing 3' AU-rich sequence,
      are unusually very stable in oocytes and become unstable only after
      fertilization. In addition, heterologous short lived mRNA, containing 3' AU-rich
      sequences, appear to be very stable when injected into Xenopus oocytes. In the
      present study, a human interferon beta (hu-IFN beta) mRNA, carrying the
      destabilizing 3' AU-rich element, was used as a probe to identify Xenopus
      proteins that specifically bind to the 3' AU-rich element as well as to study
      their relative levels during early embryonic development. While three major
      proteins that specifically bind to the 3' AU-rich element were detected in human
      SV80 cells, that naturally express hu-IFN beta (proteins termed AU-F1, F2 and
      F3), only two proteins, migrating similarly to the SV80 AU-F1 and AU-F3, were
      detected in cytoplasmic extracts from Xenopus oocytes or eggs. Following
      fertilization, the intensity of the Xenopus AU-F1 and AU-F3 proteins increased
      considerably and a new protein, corresponding to SV80 AU-F2, was also detected.
      Cyclohexamide applied either at the morula or at the early blastula stages
      reduced the intensity of the AU-binding factors, while actinomycin D did not,
      indicating that the levels of these factors during these stages are regulated
      posttranscriptionally. In contrast, application of each of these metabolic
      inhibitors at the late blastula stage increased the intensity of the AU-binding
      proteins. The possible function of these AU-binding factors in regulating the
      expression and half life of AU-rich mRNAs is discussed.

PMID- 8282102
TI  - Analysis of filamin and alpha-actinin binding to actin by the stopped flow
      method.
AB  - We ascertained by the stopped flow method the overall association rate constant,
      k+1, of filamin and alpha-actinin to fluorescently labelled filamentous actin of
      approximately 1.3 x 10(6) M-1.s-1 and approximately 1.0 x 10(6) M-1.s-1 as well
      as the overall dissociation rate constant, k-1, of approximately 0.6 s-1 and
      approximately 0.4 s-1, respectively. The overall equilibrium constant, K, for
      filamin and alpha-actinin to actin deduced from the relation K = k+1/k-1 agree
      well with published data.

PMID- 8282103
TI  - Lack of DNA enzymatic photoreactivation in HeLa cell-free extracts.
AB  - Using a DNA-protein binding assay, we have previously identified and
      characterized a UV-damaged DNA recognition protein (UVDRP) from HeLa cells
      [(1991) Nucleic Acids Res. 19, 6413-6418]. In this report, the photoreactivating
      activity of UVDRP from the yeast, Saccharomyces cerevisiae, and HeLa cells was
      investigated. Although yeast and human cells are evolutionarily different from
      each other, both UVDRPs were conserved in the sense of their biochemical
      characteristics except that the yeast UVDRP also exhibited an enzymatic
      photoreactivating activity. A mammalian expression vector plasmid DNA carrying
      the bacterial chloramphenicol acetyltransferase (CAT) gene was UV irradiated in
      vitro followed immediately by exposure to photoreactivating light, and its
      transient expression in repair-deficient xeroderma pigmentosum (XP) cells was
      investigated. More than 80% of the CAT activity was inhibited by UV irradiation,
      which was partially restored (> 60%) by a partially purified yeast photolyase. In
      contrast, HeLa cell extracts did not express a photoreactivatable recovery from
      UV-induced inhibition of the CAT activity tested in the same system. This study
      has demonstrated the potential use of the DNA-mobility shift assay to investigate
      enzymatic photoreactivation, and has indicated the absence of the repair
      mechanism in human cells.

PMID- 8282104
TI  - Abnormal Alzheimer-like phosphorylation of tau-protein by cyclin-dependent
      kinases cdk2 and cdk5.
AB  - We have shown earlier that certain proline-directed kinases such as MAP kinase or
      GSK-3 can phosphorylate tau protein in an abnormal manner reminiscent of tau from
      Alzheimer paired helical filaments [Drewes et al. (1992); Mandelkow et al.
      (1992)]. Both kinases are abundant in brain tissue and associate physically with
      microtubules through several cycles of assembly and disassembly. In this report
      we show that cdk2/cyclin A incorporates = 5 Pi into recombinant tau, and that it
      also induces the MR shift and antibody reactivity typical of Alzheimer tau.
      However, since there is no cdk2 in brain [Meyerson et al. (1992)] we looked for
      other members of this family of kinases. Using an antibody against the conserved
      N-terminus we isolated a cdk-like kinase from brain which was capable of inducing
      the Alzheimer-like characteristics in tau by phosphorylation. Its size (31 kDa),
      target specificity (proline-directed), chromatographic behavior, and abundance in
      brain suggest that this kinase is similar or identical to the neuronal cdc2-like
      kinase nclk alias PSSARLE or cdk5 [Hellmich et al. (1992); Meyerson et al.
      (1992); Xiong et al. (1992); Tsai et al. (1993)]. This was confirmed by an
      antibody specific for cdk5. Like MAP kinase and GSK-3, this kinase is physically
      associated with microtubules and can be enriched by cycles of microtubule
      assembly and disassembly. Thus, cdk5 should be regarded as another kinase that
      could be held responsible for the changes in tau protein during Alzheimer disease
      progression.

PMID- 8282105
TI  - Dephosphorylation of tau protein and Alzheimer paired helical filaments by
      calcineurin and phosphatase-2A.
AB  - We have shown previously that brain tissue contains protein kinases which can
      phosphorylate tau protein to a state reminiscent of the pathological state of
      Alzheimer paired helical filaments (PHFs); these include proline-directed kinases
      which phosphorylate SP or TP motifs (such as MAP kinase and GSK-3) [Drewes et al.
      (1992); Mandelkow et al. (1992)], as well as a novel kinase which phosphorylates
      S262 of tau protein and thereby strongly reduces the binding of tau to
      microtubules [Biernat et al. (1993)]. Here we report on the corresponding
      phosphatases in brain which normally keep the 'pathological' sites free of
      phosphate. The major phosphatases acting on tau are calcineurin and PP-2A, but
      not PP-1. Both are present and active in brain extracts, they can dephosphorylate
      recombinant tau after prior phosphorylation with either MAP kinase, GSK-3, or
      brain extract, and the course of dephosphorylation can be monitored with
      antibodies diagnostic of the pathological state of tau. Both phosphatases also
      act directly on PHF tau isolated from Alzheimer brains.

PMID- 8282106
TI  - Protein phosphatase 2A reverses inhibition of inward rectifying K+ currents by
      thyrotropin-releasing hormone in GH3 pituitary cells.
AB  - Thyrotropin-releasing hormone (TRH) reduces an inwardly rectifying K+ current in
      whole-cell voltage-clamped GH3 rat anterior pituitary cells. The TRH effect
      depends on the maintenance of a background level of Ca2+ in the pipette buffer,
      and is rapidly minimized by the intracellular dialysis produced under whole-cell
      conditions. Introduction of ADP-NH-P, a non-hydrolizable ATP analog, in the
      pipettes, nearly abolishes the TRH-evoked inhibition. The TRH-induced reduction
      of the inwardly rectifying current is significantly enhanced by incubation of
      cells 2-4 h with cholera toxin, but not by inclusion of 1 mM cyclic AMP in the
      pipettes. Under control whole-cell conditions, the reduction caused by TRH is not
      reversed upon washout of the neuropeptide. However, this effect is readily
      reversed by addition of purified catalytic subunits of protein phosphatase 2A (PP
      2Ac) but not PP-1c to the buffer used to fill the patch pipettes. Among previous
      results with PP inhibitors, these data indicate that PP2A is involved in the
      phosphorylation/dephosphorylation mechanism(s) that regulate the delayed TRH
      effects on GH3 cell excitability.

PMID- 8282107
TI  - ATMPKs: a gene family of plant MAP kinases in Arabidopsis thaliana.
AB  - We previously reported two cDNAs for MAP kinases (cATMPK1 and cATMPK2) from a
      dicot plant, Arabidopsis thaliana. We describe here the cloning and
      characterization of five additional cDNAs encoding novel MAP kinases in
      Arabidopsis, cATMPK3, cATMPK4, cATMPK5, cATMPK6, and cATMPK7. The amino acid
      residues corresponding to the sites of phosphorylation (Thr-Glu-Tyr) that are
      involved in the activation of animal MAP kinases are conserved in all the seven
      putative ATMPK proteins. Genes for MAP kinases in Arabidopsis constitute a family
      that contains more than seven members. Sequence analysis suggests that there are
      at least three subfamilies in the family of Arabidopsis genes for MAP kinases.

PMID- 8282108
TI  - Synchronous replication of SV 40 DNA in virus infected TC 7 cells induced by
      transient hypoxia.
AB  - We transiently exposed SV 40 infected TC 7 cell cultures to a reduced O2 tension
      (4-8 h, about 200 ppm relative to 10(5) Pa total pressure). Under the hypoxic
      conditions, 'working' viral replication forks were greatly retarded or stopped,
      and initiation of daughter strand synthesis in further SV 40 DNA molecules was
      suppressed. Reoxygenation released an immediate burst of SV 40 replication which
      mainly consisted of a synchronous viral replication round. This synchronous in
      vivo replication began at the known origin of replication and proceeded at normal
      rates to the known termination region. Viral replicons seemed to accumulate under
      hypoxia in a state fully prepared to begin replication immediately after recovery
      of a normal pO2. The shut-down and sudden reactivation of DNA synthesis under
      hypoxia and reoxygenation, respectively, were not accompanied by changes of the
      phosphorylation state of large T antigen. The described synchronization procedure
      can be applied to optionally large SV 40 infected cell cultures.

PMID- 8282109
TI  - Immobilizing DNA on gold via thiol modification for atomic force microscopy
      imaging in buffer solutions.
AB  - Thiols, dialkylsulfides, and dialkyldisulfides are known to be chemisorbed with
      high affinity on gold. We have prepared DNAs of specific length and sequence
      carrying thiol groups at each end. For this purpose, primers with an HS-(CH2)6
      arm at the 5'-end were used to amplify segments of plasmid DNA via the polymerase
      chain reaction. These thiolated DNAs bind strongly to the large, ultraflat Au
      surfaces which we have recently described [Hegner, M. et al. (1993) Surface Sci.
      291, 39-46], and can be imaged by AFM in liquids (aqueous solutions or propanol).
      The lengths obtained in the AFM images are consistent with the DNA being in a
      native B-conformation.

PMID- 8282110
TI  - Relaxation study of the backbone dynamics of human profilin by two-dimensional 1H
      15N NMR.
AB  - The dynamic properties of 111 backbone HN sites in uncomplexed human profilin, a
      protein of 139 residues, have been characterized by two-dimensional inverse
      detected 1H-15N NMR spectroscopy. Heteronuclear (1H)-15N nuclear Overhauser
      effects and 15N longitudinal and transverse relaxation rates have been analyzed
      in terms of model-free spectral density functions and exchange contributions to
      transverse relaxation rates. Relatively high mobilities on the nanosecond time
      scale are observed for Asp26 and Ser27, which form part of a loop connecting beta
      strands A and B, and for Thr92 through Ala95, which are in a loop connecting beta
      strands E and F. Significant exchange contributions, indicative of motions on the
      microsecond to millisecond time-scale, have been obtained for 30 residues. These
      include Leu77, Asp80 and Gly81 of a loop between beta-strands D and E, Ser84 and
      Met85 of beta-strand E, Gly121 of a loop connecting beta-strand G and the C
      terminal helix, and Gln138, which is next to the C-terminal residue Tyr139. Some
      of the regions showing high flexibility in profilin are known to be involved in
      poly-L-proline binding.

PMID- 8282111
TI  - cDNA cloning of rat proteasome subunit RC10-II, assumed to be responsible for
      trypsin-like catalytic activity.
AB  - The nucleotide sequence of a cDNA that encodes a new subunit, named RC10-II, of
      the 20S proteasome of rat embryonic brain has been determined. The polypeptide
      predicted from the open reading frame consists of 205 amino acid residues with a
      calculated molecular weight of 22,965 and isoelectric point of 6.15. Computer
      analysis showed that RC10-II belongs to the beta-type subgroup of proteasomes,
      differing clearly from alpha-type subunits of the proteasome gene family. The
      primary structure of RC10-II was found to contain the partial amino acid
      sequences of several fragments of subunit 13, which has a cysteinyl residue
      critical for the trypsin-like catalytic activity, as reported by L. R. Dick et
      al. [Biochemistry 31, 7347-7355, 1992], suggesting that RC10-II is a proteasomal
      subunit necessary for the expression of tryptic activity.

PMID- 8282112
TI  - Organisation of the chicken annexin V gene and its correlation with the tertiary
      structure of the protein.
AB  - Chicken annexin V (anchorin CII) is a collagen binding, membrane-associated
      molecule with Ca2+ channel activity. Here we report on the coding sequences,
      promoter region, size and distribution of exons, and exon-intron junctions of the
      chicken annexin V gene. It is about 25 kb long and codes for 13 short exons
      between 50 and 581 bp length. Exon sizes and locations of splice sites are almost
      completely homologous to those of the human and mouse annexin II or pigeon
      annexin I genes, although there is only 50-60% homology in the sequence of the
      corresponding proteins. The four repeat structure and symmetry of the annexin V
      as evident from sequence and X-ray analysis studies is only partially reflected
      in this highly conserved exon distribution. In the first two repeats of chicken
      annexin V the exons correlate with protein domains containing one, two, or three
      alpha-helices, while in the repeats 3 and 4 exon junctions and alpha-helical
      domains do not correlate. The analysis of the promoter structure revealed the
      absence of a typical TATA-box, but a GC-rich region which may possibly promote
      transcription from several start sites.

PMID- 8282113
TI  - gamma-Glutamylcysteinylglutamic acid--a new homologue of glutathione in maize
      seedlings exposed to cadmium.
AB  - Exposure of plants to Cd induces the appearance of several thiols based on
      glutathione and known as class III metallothioneins (or phytochelatins). A new
      tripeptide with the structure gamma-GluCysGlu accumulated in roots and shoots of
      Cd-exposed maize seedlings. This thiol was purified and identified by tandem mass
      spectrometry. The fragmentation pattern of the maize tripeptide was identical to
      that of the synthetic compound. Like glutathione, this new tripeptide may serve
      as a precursor for longer-chain peptides involved in metal detoxification through
      the formation of Cd-binding complexes.

PMID- 8282114
TI  - Effect of neutral and acidic phospholipids on mitochondrial ATP synthase
      secondary structure.
AB  - The secondary structure of delipidated and egg phosphatidylcholine or asolectin
      reconstituted mitochondrial ATP synthase complex from beef heart was investigated
      by Fourier transform infrared spectroscopy. Upon reconstitution, the infrared
      spectra of ATP synthase revealed an increase in turns and a concomitant decrease
      in beta-sheet content which occurred to a larger extent in the presence of
      asolectin rather than in the presence of egg phosphatidylcholine. These data
      correlate with kinetic data showing a higher ATPase activity of the asolectin
      reconstituted enzyme protein than the egg phosphatidylcholine reconstituted or
      delipidated enzyme complexes.

PMID- 8282115
TI  - Extended in vivo blood circulation time of fluorinated liposomes.
AB  - The clearance from blood circulation of fluorinated liposomes made with
      perfluoroalkylated phosphatidylcholines was investigated in mice using liposome
      entrapped 5(6)-carboxyfluorescein. The presence of a fluorinated core inside the
      membrane strongly retards their blood clearance. The fluorinated vesicles showed
      circulation half-lives of up to 8.6 h, which are 6-13 and 3-6 times larger than
      those of similarly sized conventional distearoylphosphatidylcholine and
      distearoylphosphatidylcholine/cholesterol liposomes, respectively. Their blood
      clearance was similar to that of some polyethylene glycol (PEG)-labelled
      'stealth' liposomes and was dose-independent in a 3.3-330 mumol/kg body weight
      dose range.

PMID- 8282116
TI  - A new application for liposomes in cancer therapy. Immunoliposomes bearing
      enzymes (immuno-enzymosomes) for site-specific activation of prodrugs.
AB  - We have tested a new type of immunoliposomes which may effectively mediate the
      targeting of enzymes to be used for site-specific prodrug activation (immuno
      enzymosomes). The enzyme beta-glucuronidase, capable of activating the prodrug
      epirubicin-glucuronide (epi-glu), was coupled to the external surface of
      immunoliposomes directed towards ovarian cancer cells. A significant increase in
      cytotoxicity of the prodrug epi-glu was shown when the in vitro cultured cancer
      cells were pretreated with these immuno-enzymosomes.

PMID- 8282117
TI  - Selective interaction of valinomycin/K+ with the cytochrome bf complex of
      chloroplasts. Synergistic effect with MOA stilbene on extent of cytochrome b563
      reduction in continuous light.
AB  - Valinomycin/K+ is shown to selectively interact at sub-micromolar concentrations
      with the cytochrome bf complex in thylakoid membranes, inducing a red shift of
      the ferrohaem b absorbance alpha-band, a slow down of post-illumination b
      reoxidation and a corresponding increase of b-reduction level in continuous
      light. These effects of valinomycin/K+ are not related to its field dissipating
      action, as they are not affected by nonactin. Presence of K+ is required.
      Phenomenologically the valinomycin/K+ effects are similar to those caused by 10
      times higher MOA stilbene nonactin. Presence of K+ is required.
      Phenomenologically the valinomycin/K+ effects are similar to those caused by 10
      times higher MOA stilbene concentrations. However, synergism is observed between
      the two inhibitors, suggesting different modes of action. When both inhibitors
      are combined more than one haem b can be reduced by illumination.

PMID- 8282118
TI  - Brefeldin A blocks protein glycosylation and RNA replication of vesicular
      stomatitis virus.
AB  - Brefeldin A is a macrolide antibiotic that interferes with membrane traffic and
      blocks the growth of several animal viruses including vesicular stomatitis virus
      (VSV). The inhibition of VSV by brefeldin A takes place at least at two different
      steps during the growth cycle: the glycosylation of VSV G protein and the
      replication of viral genomes. Our results indicate that interference with
      membrane traffic leads not only to inhibition of viral protein glycosylation, but
      also to the blockade of virus genome replication in several cytoplasmic RNA
      containing viruses.

PMID- 8282119
TI  - Long-term regulation of pyruvate dehydrogenase kinase by high-fat feeding.
      Experiments in vivo and in cultured cardiomyocytes.
AB  - The provision of the high-fat diet (47% of calories as fat) for 28 days evoked a
      significant decline in cardiac PDHa activity, together with marked increases in
      the activity of PDH kinase measured in isolated mitochondria and freshly-prepared
      cardiomyocytes from adult rats. Plasma insulin concentrations in fat-fed rats
      were not significantly different from control, but plasma NEFA concentrations
      were elevated. PDH kinase activity in cardiomyocytes from fat-fed rats fell
      substantially in culture (25 h). This decline was prevented by the inclusion of n
      octanoate and DBcAMP in combination, but not individually, in the culture medium.
      The results are discussed in relation to the role for fatty acids and insulin in
      the long-term modulation of cardiac PDH kinase activity by high-fat feeding.

PMID- 8282120
TI  - Photosynthesis modulates the sign of phototaxis of wild-type Chlamydomonas
      reinhardtii. Effects of red background illumination and 3-(3',4'-dichlorophenyl)
      1,1-dimethylurea.
AB  - We have found that the sign of phototaxis, i.e. the direction of phototactic
      migration either towards or away from the light source, of wild-type
      Chlamydomonas reinhardtii depends on its photosynthetic activity. This accounts
      for the frequently reported transient positive phototaxis that precedes a
      negative phototaxis of wild-type cells, as well as the earlier observations that
      preillumination affects the sign of phototaxis. The bases for our conclusion are
      as follows. (1) The transient nature of phototaxis was preferentially observable
      with blue-green actinic light rather than with green actinic light. (2) Red
      background light induces negative phototaxis under the actinic-light conditions
      in which, without background light, Chlamydomonas cells show exclusively positive
      phototaxis. (3) Both the effect of red background light and the transient change
      in the sign of phototaxis were inhibited by 3-(3',4'-dichlorophenyl)-1,1
      dimethylurea, a specific inhibitor of photosynthesis. The conclusion modifies the
      accepted view that photosynthesis does not link with the phototaxis of this
      microorganism, thus constituting a necessary part in elucidating mechanisms of
      algal phototaxis.

PMID- 8282121
TI  - Mechanism of Na+/H+ exchange by Escherichia coli NhaA in reconstituted
      proteoliposomes.
AB  - Purified NhaA, a Na+/H+ antiporter from Escherichia coli, reconstituted into
      proteoliposomes was used to study partial reactions catalyzed by this protein.
      Homologous Na+/Na+ exchange as well as Na+/Li+ exchange via NhaA were detected by
      monitoring the effects of external Li+ and Na+ ions on the delta pH-driven sodium
      uptake into NH4 Cl-loaded vesicles. Furthermore, a sodium counterflow reaction
      was demonstrated in proteoliposomes preloaded with non-radioactive Na+ and placed
      into the experimental buffer containing low amounts of 22Na+ under experimental
      conditions when both components of protonmotive force generated by the
      antiporter. delta psi and delta pH, were dissipated by corresponding ionophores.
      The apparent Km for sodium counterflow is 1.1 mM, and Vmax is 80 mumol/min/mg of
      protein. External Na+ accelerates the downhill efflux of 22Na+ suggesting that
      the translocation of the Na(+)-loaded form of the carrier is faster than the rest
      of the catalytic cycle.

PMID- 8282122
TI  - Calcium transport mediated by NhaA, a Na+/H+ antiporter from Escherichia coli.
AB  - In everted membrane vesicles of E. coli strain EP432/pGM42, which has only one
      Na+/H+ antiporter (NhaA), external CaCl2 inhibits dissipation of the respiration
      dependent delta pH in response to the addition of NaCl at pH 7.5, and decreases
      equilibrium concentration of the intravesicular Na+. In the NhaA proteoliposomes,
      imposition of an artificial delta pH (acid inside) leads to the several-fold
      accumulation of calcium. The apparent Km for this delta pH-driven Ca2+ uptake at
      pH 8.5 is 2 mM, and the Vmax is 1.79 mumol/min/mg of protein. Dissipation of
      delta pH causes release of calcium from the vesicles. CaCl2 was found to inhibit
      the delta pH-driven Na+ uptake mediated by reconstituted NhaA, and vice versa.
      Further, heterological Ca2+/Na+ exchange has been demonstrated in proteoliposomes
      containing NhaA. Transmembrane electric potential difference proved to drive this
      process. All these data are consistent with the assumption that NhaA can also
      catalyze Ca2+/H+ exchange.

PMID- 8282123
TI  - Modulation of the skeletal muscle sodium channel alpha-subunit by the beta 1
      subunit.
AB  - Co-expression of cloned sodium channel beta 1-subunit with the rat skeletal
      muscle-subunit (alpha microI) accelerated the macroscopic current decay, enhanced
      the current amplitude, shifted the steady state inactivation curve to more
      negative potentials and decreased the time required for complete recovery from
      inactivation. Sodium channels expressed from skeletal muscle mRNA showed a
      similar behaviour to that observed from alpha microI/beta 1, indicating that beta
      1 restores 'physiological' behaviour. Northern blot analysis revealed that the
      Na+ channel beta 1-subunit is present in high abundance (about 0.1%) in rat
      heart, brain and skeletal muscle, and the hybridization with untranslated region
      of the 'brain' beta 1 cDNA to skeletal muscle and heart mRNA indicated that the
      different Na+ channel alpha-subunits in brain, skeletal muscle and heart may
      share a common beta 1-subunit.

PMID- 8282124
TI  - The human sperm protein PH-20 has hyaluronidase activity.
AB  - The PH-20 protein present on the membrane of guinea pig sperm was characterized
      using a monoclonal antibody [(1991) J. Cell Biol. 111, 2939-2949]. We have
      isolated the cDNA encoding the human PH-20 protein from a testis library. This
      cDNA was expressed in RK 13 cells using a vaccinia virus expression system. Cells
      expressing the human PH-20 protein possess hyaluronidase activity. Treatment with
      PI-PLC releases the hyaluronidase into the the medium with a concomitant large
      increase in enzymatic activity. These results demonstrate that the human PH-20
      protein has hyaluronidase activity.

PMID- 8282125
TI  - Cyclin A-mediated inhibition of intra-Golgi transport requires p34cdc2.
AB  - An in vitro assay was used to study the role of p34cdc2 in cyclin A-mediated
      vesicular transport inhibition. It was shown that the S-phase kinase p33cdk2
      reduced the effect of cyclin A on transport assays performed with sHeLa cytosol,
      even though histone kinase was strongly activated. Also, transport with FT210
      cytosol (which is temperature-sensitive for p34cdc2) was inhibited by cyclin A
      only at the permissive temperature. However, the phosphatase inhibitor
      microcystin inhibited transport without any requirement for p34cdc2 activity.
      These results show that transport is inhibited by cyclin A via p34cdc2, and also
      by another kinase, possibly downstream of p34cdc2.

PMID- 8282126
TI  - Purification of the complex of cathepsin L and the MHC class II-associated
      invariant chain fragment from human kidney.
AB  - The complex of cathepsin L and the fragment of the MHC class II-associated
      invariant chain was purified from human kidney. M(r) of the complex, as
      determined by gel filtration, is about 40,000. Both components were identified by
      amino acid and sequence analyses. The bound invariant chain fragment is almost
      identical to the additional segment found in p41, but not in the p31 form of the
      invariant chain. The complex has significantly enhanced stability at neutral and
      slightly alkaline pH, and reduced proteolytic activity against the synthetic
      substrate Z-Phe-Arg-MCA compared to free cathepsin L. The complex exhibits no
      enzymatic activity against the protein substrate azocasein. For the first time,
      the invariant chain was found in a complex with a protein, which was not an MHC
      molecule.

PMID- 8282127
TI  - [Mechanism of insulin action--signal transductions after binding to insulin
      receptor].
AB  - Insulin binds to the alpha subunit of the insulin receptor which activates the
      tyrosine kinase in the beta subunit and tyrosine-phosphorylates the insulin
      receptor substrates-1 (IRS-1). Insulin promotes the formation of a complex
      between tyrosine-phosphorylated IRS-1 and several proteins including
      phosphoinositide(PI) 3-kinase, a heterodimer consisting of regulatory 85-kDa
      (p85) and catalytic 110-kDa (p110) subunits, GRB2 and Syp via the Src homology
      region 2 (SH2) domains. Recently, it was suggested that GRB2-Sos complex binding
      to IRS-1 was linked to Ras activation and that PI 3-kinase binding to IRS-1 was
      linked to activation of glucose transport. Since the mechanism of insulin
      stimulated glucose uptake is mainly due to translocation of glucose transporters
      from an intracellular vesicle pool to the plasma membrane, PI 3-kinase activity
      may be involved in vesicle transport in mammalian cells.

PMID- 8282128
TI  - [Thyroid and radiation].
AB  - The topic "Thyroid and Radiation" is both an old and a new area to be solved by
      human beings. The thyroid is an organ that is usually susceptible to exposure to
      ionizing radiation, both by virtue of its ability to concentrate radioiodine
      (internal radiation) and by routine medical examination: Chest X-ray, Dental X
      ray, X-irradiation of cervical lymphnodes etc. (external radiation). Iodine-131
      is widely used for the therapy of Graves' disease and thyroid cancers, of which
      the disadvantage is radiation-induced hypothyroidism but not complications of
      thyroid tumor. The thyroid gland is comparatively radioresistant, however, the
      data obtained from Hiroshima, Nagasaki and Marshall islands indicates a high
      incidence of external radiation-induced thyroid tumors as well as hypothyroidism.
      The different biological effects of internal and external radiation remains to be
      further clarified. Interestingly, recent reports demonstrate the increased number
      of thyroid cancer in children around Chernobyl in Belarus. In this review, we
      would like to introduce the effect of radiation on the thyroid gland at the
      molecular, cellular and tissue levels. Furthermore the clinical usefulness of
      iodine-131, including the safety-control for radiation exposure will be
      discussed.

PMID- 8282129
TI  - [Immunohistochemical determination of endometrial progesterone receptor (PR)
      content after intrauterine infusion of danazol in rabbits].
AB  - Danazol, an isoxazole derivative of 17 alpha-ethinyl-testosterone, has various
      effects on the female reproductive system. To examine its anti-estrogenic effects
      through the receptor system and clarify its direct effect on the endometrium in
      vivo, we applied danazol jelly into the rabbit uterine cavity. Recent studies
      performed in our laboratory using the ligand-binding assay have shown that
      danazol administered directly into the uterine cavity is absorbed by the
      endometrial tissue and exerts its anti-estrogenic effects possibly through
      progesterone receptors (PR) in the cells. In the present study we examined the
      variations in endometrial PR content during 7 days after the intrauterine
      administration of danazol into the rabbit uterine cavity. Immature female white
      rabbits were used. They were given daily subcutaneous injections of estradiol-17
      beta (E2) for 3 days after which their abdomens were opened, and danazol gel was
      infused into the lumen of the right horn and HPC-jelly was infused into the lumen
      of the left horn, as the control. Thereafter and until they were killed, the same
      daily dose of E2 was injected. They were killed 6h, 24h, 3 days, 5 days or 7 days
      after intrauterine infusion of danazol and PRs were studied immunohistochemically
      using a specific antireceptor monoclonal antibody (PR-AT 4.14). Six hours after
      danazol infusion, the PR staining in the glandular epithelium and part of the
      stroma surrounding the epithelium had declined. On day 3, PR staining declined to
      its lowest level in the glandular epithelium and stroma. On Day 5, PR staining
      had been restored in the glandular epithelium but stayed low in the
      stroma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282130
TI  - [Seven patients with hyperparathyroid crisis: emphasis on prompt
      parathyroidectomy].
AB  - Although hyperparathyroid crisis is rare, the management of this disease remains
      controversial. We analyzed the clinicopathological features and treatment outcome
      of this disease to evaluate the significance of prompt parathyroidectomy. Seven
      patients with an episode of hyperparathyroid crisis who consisted of 2.3% of all
      surgical patients of primary hyperparathyroidism were treated from 1981 to 1992
      at the Department of Endocrine Surgery, Tokyo Women's Medical College. They all
      showed grave hypercalcemia greater than 15mg/dl, renal dysfunction and
      gastrointestinal toxicity. Their ages ranged between 33 and 75 years (mean age
      49.7 years); two patients were men and five were women. Six patients had an
      adenoma, and only one had a carcinoma. The weights of the parathyroid tumors
      ranged between 3.5g and 11g, and ultrasonography disclosed an enlarged
      parathyroid gland in all patients. All of the seven patients underwent prolonged
      medical treatment (mean of durations 52 days), but four of them remained with
      hypercalcemia greater than 15mg/dl. On the other hand, the serum calcium levels
      of all patients returned to normal within five days after their operations
      without any surgical complication. Therefore, we recommend prompt
      parathyroidectomy for hyperparathyroid crisis, since medical treatment requires a
      prolonged clinical course and sometimes fails to control grave hypercalcemia.

PMID- 8282131
TI  - [Characteristics and clinical course of patients with subacute thyroiditis
      without typical signs and symptoms].
AB  - To determine the characteristics and clinical course of patients with subacute
      thyroiditis (SAT) without typical signs and symptoms, clinical and pathologic
      records of the patients were reviewed and compared with those of patients with
      typical SAT. During the past 10 years, 11 of 105 patients with SAT did not have
      enough typical features for a diagnosis of SAT (atypical SAT). They included one
      male and 10 females with the average age of 50 years. The incidence of neck pain
      as the initial symptom in the patients with atypical SAT was low (18%) compared
      with that in the patients with typical SAT (69%). Of the patients with atypical
      SAT, 42% had elevated thyroid hormone levels and 46% had suppressed TSH levels,
      whereas the percentages in the patients with typical SAT were 76% and 85%
      respectively. Nine of 11 patients were misdiagnosed as having papillary carcinoma
      by physical examination, and 4 by ultrasonography. However, aspiration cytology
      could make a precise diagnosis of SAT in 4 patients at the time of clinical
      diagnosis and 3 other patients after reevaluation. Eight patients were admitted
      to the hospital under the diagnosis of thyroid cancer and 4 underwent surgical
      resection. Differential diagnosis between atypical SAT and papillary carcinoma is
      important, and aspiration cytology could be a conclusive diagnostic tool to avoid
      unnecessary treatment.

PMID- 8282132
TI  - [The prediction of blood pressure after adrenalectomy in primary aldosteronism].
AB  - In 30-40% of patients with primary aldosteronism owing to adenoma, hypertension
      is not relieved even though a hyper-functioning adenoma has been completely
      removed. The purpose of this study is to determine whether the prognosis of
      hypertension can be evaluated pre-operatively in patients with primary
      aldosteronism. Thirteen patients (6 men, 7 women; 47 +/- 9 years old) with
      primary aldosteronism were studied and adrenalectomy was performed in all cases.
      The success of the operation was confirmed by the normalization of plasma renin
      activity (PRA), plasma aldosterone concentration (PAC) and serum potassium. Eight
      patients, 3 men and 5 women, whose blood pressure (BP) was reduced to below
      140mmHg systolic and 90mmHg diastolic at one year after the operation were
      classified as "group N" and the other 5 cases, 3 men and 2 women, remained
      hypertensive and were classified as "group H". There were no significant
      differences in the age of the patients, duration of hypertension, pretreatment
      mean BP and severity of hypertension between the two groups. Thus, it is doubtful
      that the lack of improvement of hypertension is due to the irreversible damage of
      the small arteries. Although pretreatment BP was similar in the two groups,
      systolic BP after the administration of 200mg per day of spironolactone for one
      week was significantly reduced in group N, but not in group H. Moreover, a
      significant correlation was found between mean BP after treatment with
      spironolactone and post-operative mean BP in all subjects. Pretreatment PRA was
      significantly lower in group H.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282133
TI  - [Increased plasma antidiuretic hormone in the presence of hyponatremia in primary
      hypothyroidism].
AB  - A 70-year-old woman was admitted because of disturbance of her consciousness.
      Physical examinations and laboratory data suggested hypothyroidism. Primary
      hypothyroidism was subsequently confirmed with endocrinological examinations.
      Antidiuretic hormone (ADH) levels were elevated despite severe hyponatremia. On
      admission, urinary sodium concentration was 10mEq/l. The patient was treated with
      saline intravenously; serum sodium level increased from 120 to 125mEq/l and
      urinary sodium concentration increased from 10 to 54mEq/l. Mental confusion
      developed and serum sodium level dropped with urinary sodium concentration above
      20mEq/l when thyroid replacement was started with the cessation of saline
      infusion. The patient's state of consciousness, elevated ADH levels, decreased
      serum sodium level and urinary sodium concentration were improved by thyroid
      replacement together with hydrocortisone therapy. Effects of acute water loading
      were abnormal with the administration of iodothyronine (T3) alone but were
      normalized with the administration of hydrocortisone together with T3. On
      discharge she was treated with the oral administration of levothyroxine alone.
      Pituitary hormones were normal. These results suggest that the patient was in a
      state of hypoadrenocorticism. Impaired water excretion in a state of
      hypoadrenocorticism due to hypothyroidism may give rise to an inappropriate
      secretion of ADH thereby resulting in hyponatremia, which in turn leads to
      hypotonic dehydration induced by water intoxication.

PMID- 8282134
TI  - [An incidentally found asymptomatic pheochromocytoma: a case report--successful
      removal laparoscopic adrenalectomy].
AB  - A 31-year-old male was admitted to our hospital for further examination of a
      right adrenal mass, which was incidentally discovered by abdominal ultra
      sonography in another hospital. The adrenaline and noradrenaline in the plasma
      and the adrenaline and VMA in the urine were slightly elevated, and
      catecholamines in the blood from the right adrenal vein were markedly increased.
      Glucose tolerance test showed a borderline case. Otherwise, there was no clinical
      sign. Asymptomatic pheochromocytoma originating from the right adrenal gland was
      suspected in the preoperative diagnosis. Laparoscopic right adrenalectomy was
      performed. Although the blood pressure was stable preoperatively, paroxysmal
      hypertension was observed during the tumor manipulation. Blood pressure was well
      controlled during the operation with ATP, nitroglycerin and phentolamine. Blood
      loss was less than 150ml, and there was no surgical complication. The resected
      tumor specimen was 32[28[33mm in size, weighed 14g, and histological examination
      showed typical pheochromocytoma. The post-operative course was unremarkable and
      glucose tolerance test was normalized after the operation. This is the first case
      of the successful removal of pheochromocytoma using the laparoscopic procedure.

PMID- 8282135
TI  - [Cases of Graves' disease with falsely high TSH values due to interfering
      substances which cross-link with mouse monoclonal antibodies in the TSH assay
      kits].
AB  - It has been reported that highly sensitive two-site immunometric assays
      occasionally indicate falsely high serum TSH values. A possible reason for this
      is that heterophilic antibodies interfere with these assays. Recently we had a
      patient in whom the Delfia TSH kit falsely indicated an elevated serum TSH value.
      A 29-year-old female was diagnosed as having Graves' disease and was referred to
      Ito Hospital for surgical treatment. Her thyroid hormone values were distinctly
      high two months before admission (FT3: 20.7pmol/L, FT4: 42.3pmol/L), but her
      serum TSH level was normal (1.1mU/l). She was clinically hyperthyroid, and T3 and
      T4 values determined after ethanol extraction and T3 or T4 analog binding rates
      did not indicate the presence of T3 or T4 antibodies. Her TSH value became
      undetectable when mouse IgG was added to the assay. These results suggested that
      the "normal" serum TSH value was caused by interfering substances such as anti
      mouse IgG antibodies which had cross-linked with mouse monoclonal antibodies in
      the Delfia TSH kit. Another 12 patients who were suspected of having the
      interfering substances were examined because of the discordance between TSH
      values and thyroid hormone values. All of the serum TSH values measured using the
      DELFIA TSH kit decreased when mouse IgG was added. In another case, the presence
      of serum TSH could not be detected using the Delfia TSH kit but could be measured
      using the RIABEAD II TSH kit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282136
TI  - [Intracellular mechanism of interleukin-1 alpha-induced prostaglandin E2 (PGE2)
      production in a mouse osteoblast-like cell line and the possible involvement of
      protein kinase A and protein kinase C].
AB  - Interleukin-1 (IL-1) is known to be a potent stimulator of bone resorption. The
      effect of IL-1 has been shown to be mediated, at least in part, by IL-1-induced
      prostaglandin (PG) E2 production in osteoblasts. The intracellular signal
      transduction mechanism of IL-1 in the PG production, however, is unknown. In the
      present study using a mouse osteoblastic cell line, MC3T3-E1 (MC), the possible
      involvement of two representative signal transduction pathways, protein kinase A
      (PKA) or protein kinase C (PKC)-dependent pathway in the IL-1 alpha stimulated
      PGE2 production, was investigated. MC produced PGE2 30 min after the IL-1
      stimulation. This was inhibited with cycloheximide, suggesting the involvement of
      de novo protein synthesis. The IL-1-induced PGE2 production was inhibited by H-7
      in a dose dependent manner. Since H-7 is known to inhibit PKA as well as PKC, a
      more specific inhibitor of PKA KT5720 or staurosporin was used to determine the
      respective role of PKA or PKC in the production of PGE2. KT5720 inhibited the IL
      1-induced PGE2 production in MC in a dose dependent fashion. Similarly,
      staurosporin inhibited the IL-1-induced PGE2 production in MC in a dose dependent
      manner. The effect of the activity of PKA or PKC on the production of PGE2 was
      also investigated. A stimulator of PKA, 8-bromoadenosine 3'5'-cyclicmonophosphate
      (8-Br-cAMP), as well as a stimulator of PKC phorbol 12-myristate 13-acetate (PMA)
      induced PGE2 production in MC. The effect of these agents on the PGE2 production
      was additive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282137
TI  - Fetal transcutaneous PCO2 measurements during labour.
AB  - The departments of Obstetrics and Gynaecology of the Universities of Bonn and
      Copenhagen and the Free University of Amsterdam cooperated in the European
      Community Concerted Action Project 'New methods for Perinatal Surveillance'. In
      95 patients fetal transcutaneous PCO2 (tcPCO2) recording (measuring temperature
      41 degrees C) during labour was evaluated regarding its clinical applicability.
      During the first stage of labour fetal tcPCO2 was rather stable at a level of 7.3
      +/- 1.4 kPa. In the second stage there were marked differences between the three
      subpopulations. In the first stage of labour the correlation between tcPCO2 and
      PCO2 in fetal blood samples was 0.38 (P = 0.02) and in the second stage -0.20 (P
      = 0.36). The correlation of fetal tcPCO2 with umbilical artery PCO2 was 0.30 (P =
      0.01) and with pH -0.30 (P = 0.01). Using a fetal tcPCO2 level of 8.0 kPa as a
      cut-off point to predict an umbilical artery pH less then 7.20, sensitivity was
      88%, specificity 65%, positive predictive value 29% and negative predictive value
      97%. The likelihood ratio of a positive test was 2.47 and of a negative test
      0.13. It is concluded that fetal tcPCO2 possibly can be an additional tool to
      exclude fetal acidosis. In case of values above 8.0 kPa further evaluation of the
      fetal acid-base balance is indicated.

PMID- 8282138
TI  - Is lung maturation related to fetal growth in diabetic or hypertensive
      pregnancies?
AB  - The purpose of this study was to determine whether infants sufficiently affected
      by maternal diabetes or hypertension to exhibit abnormal growth (macrosomia,
      growth retardation) would also display significant alteration in timing of
      pulmonary maturity (delay or acceleration, respectively). We studied 874
      consecutive women with fetal pulmonary maturity testing prior to delivery.
      Patients were stratified by birth weight into fetal size categories (small for
      gestational age [SGA], appropriate for gestational age [AGA], large for
      gestational age [LGA]). Cases were compared based on maternal disease, fetal size
      categories and pulmonary maturity testing results. Pulmonary maturity rates based
      on both phosphatidylglycerol (PG) and lecithin/sphingomyelin ratio (L/S) did not
      differ between term LGA infants of diabetic mothers (97%) and term LGA (80%) or
      AGA (97%) infants of non-diabetic, non-hypertensive mothers. When compared based
      on PG alone, there was no difference between the rate of positive PG in term AGA
      infants of non-hypertensive, non-diabetic mothers (75%) and that seen in the
      other pregnancy groups (33-80%). Breakdown by gestational age revealed no
      significant differences in maturity rates between the study groups. Macrosomic
      diabetic infants and growth-retarded hypertensive infants are no different from
      controls in their timing of fetal pulmonary maturation.

PMID- 8282139
TI  - Hormonal factors and prognosis in epithelial ovarian cancer: a multivariate
      analysis.
AB  - When a significantly lower follicle stimulating hormone (FSH) level was found in
      patients with epithelial ovarian carcinoma, it was decided to analyze the
      influence of hormonal factors on prognosis. Thirteen factors were tested for
      prognostic significance in 35 women with epithelial ovarian carcinoma. Age, FIGO
      stage, histopathological grade, residual tumor, treatment, gonadotrophins and
      steroid hormones were tested. By univariate log-rank testing a significantly
      shorter survival time was found for patients with ascending FIGO-stage, residual
      tumor mass, estradiol < 0.10 nmol/l, progesterone < 2.0 nmol/l and DHEAS < 1300
      nmol/l. In the Cox model the independently significant prognostic factors found
      were residual tumor mass (P < 0.001) with a risk estimate of 2.65, progesterone
      (P < 0.05) with a risk estimate of 0.29 for a progesterone level > 2.0 nmol/l and
      total testosterone (P < 0.03) with a risk estimate of 0.29 for a total
      testosterone level > 1.15 nmol/l. The present findings, together with the
      assumption that an elevated gonadotrophin level may induce ovarian tumor growth
      (the gonadotrophin theory), earlier findings of estrogen and progesterone
      receptors in human ovarian cancer, and the in vitro demonstration of
      gonadotrophin-growth-stimulation of human malignant epithelial tumors, justify a
      thorough investigation of the interaction between steroid hormones and receptors,
      gonadotrophins, tumor bulk and survival in future research protocols.

PMID- 8282140
TI  - The effect of estriol on the cytology of urethra and vagina in postmenopausal
      women with genito-urinary symptoms.
AB  - In a double-blind, randomised trial, 62 postmenopausal women with genito-urinary
      symptoms were treated with oestriol or matching placebo for 4 weeks. Estriol
      (Synapause-E3, Nourypharma Nederland) was given orally for 4 weeks in a single
      daily dose (8 mg/day first week, 4 mg/day second and third week, 2 mg/day fourth
      week). The influence of estriol on the vaginal and urethral epithelium was
      assessed by using the karyopycnotic index and the maturation value. As we
      expected, it was confirmed that estriol has a remarkably beneficial effect on the
      vaginal epithelium. This also applies to the epithelium of the urethra, although
      the effect is much less obvious.

PMID- 8282141
TI  - Estrogen and progesterone receptors in the uterine artery of rats during and
      after pregnancy.
AB  - Changes in the level of estrogen and progesterone receptors in the uterine artery
      of the rat were studied during pregnancy in order to evaluate the estrogen
      dependency of this artery. The weight of the uterine artery and its content of
      estrogen and progesterone receptors were measured. The steroid receptor content
      was also measured in the uterus and aorta as the tissues of these organs are
      estrogen-responsive and non-responsive, respectively. The uterine artery weight
      increased more than fourfold up to the middle of pregnancy and towards the end of
      pregnancy increased even further. The increase in weight was parallel to the
      increase in the level of plasma 17 beta-estradiol. During pregnancy a dramatic
      increase was detected in the number of uterine artery estrogen receptors. The
      estrogen receptor level was highest at term pregnancy, and following birth
      decreased to a low value. The level of progesterone receptors in the uterine
      artery increased modestly, though significantly, during pregnancy, and rose
      steeply at puerperium. No meaningful changes were seen in the aorta. The changes
      in estrogen and progesterone receptor levels in the rat uterine artery wall
      during and after pregnancy may suggest estrogen dependency of this tissue.

PMID- 8282142
TI  - Effect of chronic intermittent stress on rat pregnancy and postnatal development.
AB  - The present study evaluates the effect of chronic intermittent cold-swimming
      stress on body weight gain of pregnant rats and subsequent development of the
      offsprings after birth, till peripubertal stage. When stress was administered
      during the first half (1-11 days) of gestation, weight gain of pregnant rats was
      significantly lower at the 9th and 11th days (P < 0.05 vs. control,
      respectively). No differences of weight gain in comparison with control rats were
      found at term gestation in pregnant rats exposed to stress continuously.
      Similarly, stress administered, starting from 12th day till term gestation, had
      no effect on weight gain. Even though weight gain of pregnant rats during the
      second half of pregnancy in group stress 1-11 was restored to normal values, a
      high mortality rate of neonates 1, 2 and 3 weeks after birth was found in this
      group (P < 0.02, 0.01 and 0.001 vs. controls). There was no significant
      difference between stressed and control groups with respect to the number or body
      weight of litters, as well as weight gain of neonates during the first 21 days of
      life. In addition, in offsprings from all stressed groups, a high number of small
      for date animals was found after 14 days of life, and 74.4% of these small for
      date animals died during the peripubertal period. The present data demonstrate
      that the exposure to stress in utero may induce damaging effects on postnatal
      development.

PMID- 8282143
TI  - Follicular fluid inhibin levels in relation to age in patients in an in vitro
      fertilization and embryo transfer programme.
AB  - Inhibin (INH), oestradiol (E2) and progesterone (P) were measured in the
      follicular fluid (FF) of 22 patients 28-38 years old (Group A) and 11 patients 43
      47 years old (Group B) who had received gonadotrophin stimulation in an in vitro
      fertilization and embryo transfer (IVF-ET) programme. The results indicated that
      INH, E2 and P levels were significantly lower and the E2/P ratio was higher in FF
      of Group B patients (older women) compared to those of Group A. There were six
      single pregnancies among patients of Group A. No difference was observed in
      follicular fluid INH, E2 and P levels as well as in E2/P ratio between pregnant
      and non-pregnant patients of Group A (Group A1 and Group A2, respectively). A
      positive correlation was found between FF concentrations of E2 and P, E2 and INH
      and P and INH in the three Groups and a negative one between INH and the E2/P
      ratio in Group B. It seems likely that ovarian INH and E2 production are
      controlled by different mechanisms and that INH response to ovarian
      hyperstimulation is altered by advancing age.

PMID- 8282144
TI  - Ergotamine-induced fetal stress: review of side effects of ergot alkaloids during
      pregnancy.
AB  - A case of sudden fetal stress after accidental administration of ergotamine
      tartrate (2 mg) suppository is reported. Caesarean section was performed because
      of unexplained fetal stress. In retrospect, we conclude that it is likely that
      sudden fetal stress was caused by the severe vasoconstrictive effect of
      ergotamine. The side effects of ergot derivatives during pregnancy are discussed.

PMID- 8282145
TI  - Congenital heart block in one of the HLA identical twins.
AB  - A case of HLA identical twins with one affected by congenital heart block is
      reported. Both twins, as their mother, had more than 12-fold higher anti-Ro
      antibody titers compared to healthy controls, but no differences were observed
      between the affected and the healthy baby. It is possible that there is a third
      factor causing the manifestation of this disease.

PMID- 8282146
TI  - Panic disorder masquerading as pre-eclampsia.
AB  - Panic disorder is a specific psychiatric entity with specific and successful
      treatments. A parturient patient with sudden hypertension, hyperreflexia and
      headache was diagnosed with pre-eclampsia and treated with magnesium sulphate.
      Further attacks after discharge were recognized as panic attacks, and resolved
      with the anti-depressant imipramine.

PMID- 8282148
TI  - XXVth Meeting of the European Pancreatic Club. Paris, France, October 20-23,
      1993. Abstracts.

PMID- 8282147
TI  - DNA aneuploidy in ectopic pregnancy and spontaneous abortions.
AB  - The nuclear DNA content of 55 ectopic tubal pregnancies was studied by flow
      cytometry from paraffin embedded tissue blocks. An abnormal amount of DNA content
      was found in 24% of the cases. This was a significantly higher percentage than
      encountered in 92 spontaneous abortions studied by the same method in the same
      population (8%, P = 0.01). The result indicates that, in addition to the maternal
      factors, abnormal embryogenesis with grave chromosomal aberrations may play a
      major role in the etiology of ectopic pregnancy.

PMID- 8282149
TI  - Prevention: the big questions.

PMID- 8282150
TI  - The impact of a mass communications campaign on the reported management of asthma
      by general practitioners.
AB  - There have been recent campaigns in many countries to address the increasing
      morbidity and mortality of asthma by promoting better management. This study
      aimed to evaluate the National Asthma Campaign (NAC), in Australia, and to assess
      the extent of its impact on reported asthma management. It was a cross-sectional,
      before and after study using the same self-administered questionnaire in postal
      surveys involving 472 general practitioners (GPs) before the campaign and 540 GPs
      6 months after the start of the campaign. Both samples were random samples of GPs
      in active practice. The campaign was effective in making GPs more aware of the
      principles of good asthma management. Most (74%) GPs in the post-campaign survey
      were aware of a current asthma education programme compared with 53% in the pre
      campaign survey, although only 23% cited the NAC. After the campaign there were
      significant improvements reported in airway function measurement practices, the
      use of preventive therapy and the use of written action plans.

PMID- 8282151
TI  - The influence of workload on the mental state of the primary health care
      physician.
AB  - The work factors involved in physicians' mental workload were analysed. The study
      settings were 116 physicians (general practitioners, paediatricians and residents
      in family programmes working in out-patient clinics) (Primary Health Care
      Centres) in Spain. The questionnaire used measured the mental workload and the
      work activity over a period of 5 days. The mental workload covered seven
      dimensions: mental effort, physical effort, difficulty, priority, modify
      standards of visit, overlap, and stress. Its Cronbach's alpha coefficient was
      0.80. The mental workload correlated positively with all variables measuring the
      workload activity. However, when the multiple regression analysis (stepwise met)
      was assessed, only the number of room visits, the referrals by nurse to
      physician, the room emergencies, the level of administrative tasks, the patients
      with complex pathologies, and the workload adequacy remained significant. The
      physicians' years of experience did not correlate with mental workload. The
      influence of diverse work activities in each of the mental workload dimensions
      was investigated. We conclude that the number of patient visits and
      organizational factors determine physicians' mental workload.

PMID- 8282152
TI  - The incidence and outcome of rectal bleeding in general practice.
AB  - The objective of the studies reported in this paper was to determine the
      incidence as well as the final diagnostic outcome of rectal bleeding presenting
      in general practice. Because of the wide variety observed in incidence rates
      among 83 general practitioners (GPs) in the first study (A) an additional study
      (B) was undertaken. In study B with 10 GPs special efforts were made to maximize
      the catchment rate. The mean 'consultation incidence rate' was 7 per 1000 people
      per year. A follow-up period of at least 1 year was applied to establish the
      final diagnostic conclusion. Occurrence of colorectal cancer was found in 3% of
      patients with rectal bleeding. This may represent an overestimation of the prior
      probability since there was a selection in favour of patients with clinically
      relevant rectal bleeding. In about 90% of patients rectal bleeding was related to
      minor ailments or self-limiting disorders. Further study on predictive values of
      (combinations of) other signs and symptoms is necessary to develop clinical
      recommendations.

PMID- 8282153
TI  - Double-contrast barium enema versus colonoscopy in the diagnosis of neoplastic
      disorders: aspects of decision-making in general practice.
AB  - A total of 190 patients, referred by general practitioners for a double-contrast
      barium enema, were subsequently examined with colonoscopy. With colonoscopy and
      histology as the reference standard, sensitivity, specificity, positive and
      negative predictive values, and accuracy for the radiological detection of cancer
      and polyps were calculated. No cancer was overlooked by the radiological
      examination, but there were four false positives. The overall sensitivity for
      polyps was 70%, increasing to 81% for polyps > or = 10 mm. The predictive value
      was 93-97% for the exclusion of polyps. The caecum was reached in 187 patients by
      double-contrast barium enema (98%) and in 164 patients (86%) by colonoscopy.
      Lesions in four of 12 patients who had radiological changes were undetected at
      the first colonoscopy, but a repeat examination showed polyps > or = 10 mm in
      size. Although colonoscopy is a more sensitive technique for the detection of
      small mucosal lesions, the general practitioners may, in the vast majority of
      patients, rely on a negative result for polyps and cancer obtained by the double
      contrast barium enema. The latter is linked with a number of false-positive
      cases, while colonoscopy is associated with technical difficulties; both
      techniques may lead to repeated examinations, regardless of which was the first
      choice.

PMID- 8282154
TI  - The development of general practice in China.
AB  - The concepts and principles of general practice are consistent with Chinese
      cultural values; the leading authorities at the General Practice Training Centre
      are extremely enthusiastic about the general practice movement; the Ministry of
      Public Health is totally supportive of the general practice training; the
      medical/allied health professionals are eager to participate in general practice
      activities; and general practice certainly is responsive to public expectations.
      General practice will be flourishing and prosperous in China; however, there may
      be times when the specialty of general practice in China experiences growing
      pains with obstacles. The experiences gained from the development of general
      practice training programmes in Taiwan and other countries to handle the
      obstacles are of tremendous value to the development of general practice in
      China. It is expected that communication and exchange between the general
      practice educators of Taiwan and China will play an important role in the further
      development of general practice in China.

PMID- 8282155
TI  - Mortality rates in a cardiovascular 'low-risk' population in rural Crete.
AB  - A research project in primary health care has been in progress since 1988 in an
      agricultural area of Crete, with the aim of surveying the cardiovascular risk
      profile and following the incidence of cardiovascular disease in the population
      over time. In the present paper we have investigated the mortality rates and the
      causes of death in 1989 and 1990 of the population of the Agios Vassilios county
      (n = 7758). Furthermore, whenever possible, we have checked the accuracy of the
      certified causes of death against the case record system introduced in 1988 in
      the health centre. During 1989 and 1990, 267 subjects died in the research area,
      234 of whom were > 65 years old. Diseases of the circulatory system (mostly
      congestive heart failure) accounted for 46% of all deaths. The corresponding
      figure for neoplasms was 18%. The standardized mortality from ischaemic heart
      disease was found to be very low in both men and women, 37.9 and 41.9 per 100,000
      per year, respectively, in comparison with that of Greece as a whole in 1989,
      140.0 and 59.5, respectively. These figures were considerably lower than those
      reported in 1988 from for example Sweden, 303.6 and 153.3, respectively. The
      standardized mortality from cerebrovascular disease in Agios Vassilios county was
      found to be somewhat lower than the national figures in 1989, 118.1 and 107.0 in
      males and females versus 135.7 and 142.1, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8282156
TI  - Is there a relationship between a mother's mental state and consulting the doctor
      by the family? A study in a military general practice.
AB  - A total of 174 families of service personnel with children between 3 and 6 years
      of age were studied over a 6 month period. All contacts with the general
      practitioner, both in and out of hours together with the local casualty
      department were recorded. Mothers of the children were posted a specially
      designed questionnaire to measure how seriously they perceived various childhood
      symptoms to be and a copy of the general health questionnaire, 28 question
      version (GHQ 28). The perceived severity questionnaire had been piloted
      previously in a neighbouring practice. The overall response rate was 77%.
      Analyses of the data showed that the factors most significantly associated with a
      child's consultation frequency were the psychological state of the mother, the
      mother's own consultation frequency and the number of children in the family; the
      last being an inverse relationship. No evidence was found to suggest that the
      perception of the severity of illness varied with the psychological state of the
      mother. In addition, the childhood consultation rate was not influenced by the
      mother's perception of the severity of childhood illness as measured by the
      perceived severity questionnaire. Other factors such as the age of the mother or
      child, within the age range studied, were not found to be significantly related
      to the child's frequency of consulting. A mother's own consultation frequency was
      highly correlated with her GHQ 28 score, but more specifically with the
      subsections that scored for depression and somatic symptoms. From the study,
      doctors who see children should seriously consider the main reasons for a child's
      consultation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282157
TI  - The inventory to diagnose depression (IDD) in primary care patients.
AB  - Major depressive disorder (MDD) is highly prevalent in ambulatory primary care
      patients. Severe functional impairment and risk of suicide are features of the
      condition. Although treatment can reduce morbidity, detection of MDD by primary
      care physicians is suboptimal. The aim of this study is to assess the inventory
      to diagnose depression (IDD) as compared with clinical psychiatric assessment for
      case finding in primary care patients. Adult members of an Israeli kibbutz
      (communal settlement), where all psychiatric diagnoses made by the family
      physician are confirmed by psychiatric consultation, were asked to complete the
      IDD; a 22 question, self-administered questionnaire. Patients whose scores
      indicated MDD, if not previously diagnosed, were also referred to psychiatrists.
      Patients' medical charts were reviewed for the diagnosis of MDD and response to
      therapy prior to the administration of the IDD. Of the sample of 312 patients,
      207 (66.3%) completed the IDD. Refusers were younger (P = 0.04), more likely to
      be native born Israelis (P = 0.02), and had a higher prevalence of known MDD (P =
      0.05) than participants. MDD by IDD scores was present in seven patients, in
      three of whom the diagnosis had previously been established; the other four were
      newly diagnosed. In the three previously diagnosed patients, one (metastatic
      carcinoma) refused treatment and two were receiving psychotherapy; all were
      clinically depressed. Four additional previously diagnosed patients whose IDD
      scores were insufficient for MDD had had a successful response to current
      therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282158
TI  - Benzodiazepine prescribing in a community in crisis.
AB  - A study of the rate of benzodiazepine prescribing was made in one primary care
      clinic in Israel during the period of the Gulf War. The number of benzodiazepine
      prescriptions rose sharply at the start of the war and declined before the cease
      fire. This rise in prescribing was both absolute and relative to total
      prescriptions dispensed. The war appeared to represent a transient emotional
      crisis in the community. There was no evidence of dependence on anxiolytics
      following the termination of hostilities. There were some signs that the
      population adapted to the situation, needing fewer tranquilizers before the war
      ended.

PMID- 8282159
TI  - Application of a preventive programme in the Spanish primary health care system.
AB  - In this study the main objective was to evaluate a programme on prevention
      activities and its promotion in the Primary Health Care (PAPPS) in our health
      centre. We made a descriptive study of a population of 20,000 inhabitants, taking
      100 histories at random from the total at the centre. The studied variables were:
      age, sex, blood pressure, alcohol, tobacco, height and weight. The more important
      results were: 62% of the histories had reported the variables, being more
      frequently recorded in older patients. The least frequently reported variable was
      weight (CI 95%: 37%, 19%) and the highest was smoking (CI 95%: 49%, 29%). There
      were no sex differences except for smoking that was significantly higher in
      women. In conclusion it is necessary to evaluate primary health care through the
      national established programmes, to reach a better standard of health.

PMID- 8282160
TI  - Loss of function in patients with acute low-back pain.

PMID- 8282161
TI  - How patients look at drug therapy: consequences for therapy negotiations in
      medical consultations.

PMID- 8282162
TI  - Factor analysis as a tool in primary care research.
AB  - Research in primary health care is increasingly relying on questionnaires and
      surveys to address relevant research questions. In many cases, a variety of items
      are assessed representing attitude sets or multidimensional constructs. Factor
      analysis is an effective and efficient method for identifying underlying
      dimensions in a group of variables. In addition, factor analysis allows the
      investigator to reduce a large set of original variables to a smaller set of new
      composite factors for use in future investigations, with a minimum loss of
      information. The issues and methods of factor analysis are described and
      illustrated with data from an investigation of a medical school's attitudes
      toward gifts from industry.

PMID- 8282163
TI  - An analysis of review articles published in primary care journals.
AB  - Review articles play an important role in synthesizing primary research for
      dissemination to clinicians. In a previous study it was found that many review
      articles appearing in leading peer-reviewed general medical journals are not
      prepared systematically. Given that review articles feature prominently in
      primary care journals, this study assessed the extent to which review articles
      published in the seven main primary care journals during 1991 had been assembled
      using a systematic and scientific approach. A total of 28 review articles were
      identified covering a wide range of subject areas. However, when standard
      criteria were used to assess their methodological rigour, only 25% of the
      articles had a total score of more than 8 points (out of a possible 16). The
      validity of any conclusions or recommendations made in a poorly assembled review
      need to be carefully examined. Improving the methodological standards by which
      reviews are assembled in primary care journals should be seen as both a challenge
      and a priority.

PMID- 8282164
TI  - Improving the response rates in primary care research. Some methods used in a
      survey on stress in general practice since the new contract (1990).
AB  - This paper describes some methods used to improve the response rates in a survey
      on "stress in general practice since the new contract", and it discusses some of
      the literature on this problem. The methodology is a detailed account of steps
      taken to improve the presentation to the general practitioner (GP) in the letter,
      the forms and postal procedures that accompany the questionnaire, so as to focus
      the doctor's attention. The changes made in the reminder attempts are explained
      and the results noted. It is argued that it is important to attempt to improve
      rates to make the survey as meaningful as possible. These methods may be of
      particular use in primary care research.

PMID- 8282165
TI  - The productive use of threat.

PMID- 8282166
TI  - Cytological and biochemical studies on chromaffin cells in the head kidney of
      Gasterosteus aculeatus (Teleostei, Gasterosteidae).
AB  - Adrenal chromaffin cells in the head kidney of the stickleback Gasterosteus
      aculeatus were examined by ultrastructural analysis and determination, by HPLC,
      of the catecholamine content (adrenaline, noradrenaline, and dopamine).
      Chromaffin cells are characterized by the presence of membrane-bound vesicles and
      two cell types were identified: (i) those with vesicles containing a strongly
      electron-dense core; and (ii) those with vesicles that are completely electron
      lucent or containing smaller and less-dense granules. HPLC analysis revealed the
      presence of adrenaline and noradrenaline in both right and left head kidneys.
      Dopamine was not detected. Cytological and biochemical data suggest that the
      cells with electron-dense granules contain noradrenaline and those with electron
      lucent vesicles contain adrenaline.

PMID- 8282167
TI  - Serotonin N-acetyltransferase (NAT) activity and melatonin levels in the frog
      retina are not correlated during the seasonal cycle.
AB  - The seasonal pattern of daily serotonin N-acetyltransferase (NAT) and melatonin
      rhythms in the lateral eye of Rana perezi has been characterized to assess any
      seasonal relationship between enzymatic activity and melatonin production and to
      evaluate the photothermal responses of such rhythms. In winter there was no daily
      rhythm either in NAT activity or in melatonin production, although the highest
      values of NAT activity and lowest melatonin concentrations were measured at this
      time. Ocular melatonin showed a high-amplitude diurnal rhythm during the summer,
      whereas a low-amplitude rhythm was observed in spring and autumn. Diurnal
      melatonin levels were temperature-independent; however, nocturnal melatonin
      production significantly increased with temperature. Ocular NAT was always higher
      at lower than at higher temperatures (two- to threefold), both at night and
      during the day. As suggested for pineal melatonin production in other
      poikilotherm species, photoperiod controls the duration of the melatonin
      nocturnal rise, whereas temperature regulates the amplitude of the daily
      melatonin rhythm in the frog retina. The lack of correlation between daily NAT
      and melatonin rhythms in the frog retina may result from the high thermal
      sensitivity of the ocular NAT and a temperature-dependent inhibition substrate of
      NAT activity.

PMID- 8282168
TI  - Seasonal changes in plasma levels of steroid hormones in an asynchronous fish the
      gudgeon Gobio gobio L. (Teleostei, Cyprinidae).
AB  - Annual changes in plasma of estradiol-17 beta, testosterone, and 17,20 beta
      dihydroxy-4-pregnen-3-one concentrations were measured, by radioimmunoassay, in
      female gudgeon Gobio gobio a fish which has an asynchronous-type ovary containing
      oocytes at various stages of development and spawns several times during the
      reproductive period. The gonadosomatic index and the relation between stages of
      maturity and steroid concentrations were also followed during the reproductive
      cycle. Plasma levels of estradiol-17 beta, testosterone, and 17,20 beta-dihydroxy
      4-pregnen-3-one were low from October to April and increased rapidly in May to
      reach 0.61 +/- 0.31; 2.3 +/- 0.42; and 3.17 +/- 0.68 ng/ml, respectively.
      Elevated levels were maintained during spawning when vitellogenic oocytes are
      present alongside oocytes in final maturation. Histological analysis of the ovary
      indicated that an important number of spawnings has occurred since the proportion
      of oocytes in final maturation stage was very low (less than 1%). Fish in the
      regressive phase also presented high steroid levels. The vitellogenic oocytes in
      preovulatory atresia and the postovulatory follicles may be responsible for these
      events.

PMID- 8282169
TI  - Immunocytochemical demonstration of chicken hypophyseal thyrotropes and
      development of a radioimmunological indicator for chicken TSH using monoclonal
      and polyclonal homologous antibodies in a subtractive strategy.
AB  - The production and characterization of monoclonal antibodies (mAbs) toward the
      chicken pituitary glycoproteins are described. MAbs were first subdivided on an
      immunocytochemical (ICC) basis: one category of mAbs reacts with both thyrotropic
      and gonadotropic cells whereas another stains exclusively gonadotropic cells. The
      hypothesis that the former are anti-glycoprotein alpha and that the latter are
      anti-beta LH and/or anti-beta FSH mAbs was further elaborated in a homologous
      tracer binding assay. The putative anti-beta gonadotropin mAbs exclusively
      recognize iodinated USDA-cLH-I-1, whereas the supposed anti-alpha mAbs react with
      both USDA-cLH-I-1 and USDA-cFSH-I-1. The ICC localization of pituitary
      thyrotropes has been achieved in a double-staining protocol using an anti-LH mAb
      to subtract specifically the gonadotropic cells from the complete alpha-subunit
      containing cell population. The result is a strictly cephalic cell population
      that is densely granulated in hyperthyroid and hardly detectable in hypothyroid
      birds. A similar subtractive approach was used to develop a thyroid-stimulating
      hormone (TSH)-indicator in RIA. The total titer of alpha-containing molecules is
      first quantified with an anti-alpha mAb. The contribution of both LH and FSH to
      this titer is then measured by homologous USDA-RIA and subtracted from the total
      alpha-immunoreactivity to give an indication of the TSH level of the sample. The
      direct effect of thyroid-releasing hormone on pituitary TSH release in vitro in
      juvenile chicks and the effect of hypo- and hyperthyroidism on circulating TSH
      levels in vivo in juvenile broilers have been demonstrated.

PMID- 8282170
TI  - Parathyroid hormone-related protein is a factor in normal fish pituitary.
AB  - Using antibodies to the amino-terminal region of human parathyroid hormone
      related protein (PTHrP) we have demonstrated PTHrP immunoreactivity in
      pituitaries and plasma of the sea bream (Sparus aurata). Pituitary cells at two
      distinct locations contained immunodetectable PTHrP; an anterior group in the
      rostral pars distalis which also contained immunoreactive thyroid stimulating
      hormone (TSH), and a posterior group lying at the border of the pars intermedia
      and proximal pars distalis between cells which stained with antibody to human
      corticotrophin-like intermediate lobe peptide. By Western blot analysis pituitary
      extracts contained two immunoreactive isoforms of PTHrP, one of 29 kDa and the
      other of 26 kDa. Media of pituitaries incubated for up to 14 days in Krebs-Ringer
      bicarbonate also had several isoforms of immunodetectable PTHrP, two of them
      corresponding to the 29- and 26-kDa molecular forms but there were in addition
      both larger and smaller molecules. The concentration of PTHrP in sea bream plasma
      was comparable with levels observed in human subjects with humoral hypercalcaemia
      of malignancy. There was no reaction between pituitary cells or pituitary
      extracts and antibody to human parathyroid hormone. Thus sea bream pituitary
      contains immunoreactive PTHrP, which appears to be released into medium during in
      vitro incubation and which may be a significant source of plasma immunoreactive
      PTHrP in vivo.

PMID- 8282171
TI  - Roles of adrenal and gonadal steroids and season in uropygial gland function in
      male pigeons, Columba livia.
AB  - To gauge the relative regulative roles of adrenal, gonadal, and thyroid hormones
      on uropygial gland of male adult pigeons, morphometric, histological, and
      histochemical observations have been made on a seasonal basis in normal as well
      as experimentally manipulated birds. Normal birds showed a parallel adrenal
      gonadal-uropygial relationship and inverse adrenal-thyroid, thyroid-gonadal, and
      thyroid-uropygial relationships. Induced hypocorticalism by dexamethasone in the
      breeding season and hypercorticalism by ACTH or corticosterone treatment in the
      nonbreeding season were marked by inhibitory and stimulatory changes respectively
      in the uropygial gland and testis and by inverse thyroid activity. Further,
      cyproterone acetate treatment in the breeding season completely suppressed
      testicular functions and increased thyroid activity without affecting either
      adrenal or uropygial weight, structure, and functions. Based on the observations
      it is concluded that adrenal steroids are principally involved in regulating the
      uropygial gland while the gonadal steroids are involved in qualitative aspects of
      secretion during the breeding phase and thyroid hormones in maintaining the
      general metabolic profile.

PMID- 8282172
TI  - Changes in the activities of steroidogenic enzymes during the development of
      ovarian follicles in Rana nigromaculata.
AB  - Earlier studies showed that the predominant steroid (estradiol [E2], testosterone
      [T], progesterone [P4]) secreted by in vitro cultured amphibian (Rana
      nigromaculata) ovarian follicles varied with their size. E2 was mainly produced
      by medium-sized follicles, T by intermediate-sized follicles, and P4 by the
      largest follicles. Experiments were carried out to ascertain whether the
      activities of steroidogenic enzymes changed during follicle development and were
      responsive to gonadotropic stimulation. Enzyme activities were measured
      indirectly by monitoring conversion of exogenously added substrates to products
      during in vitro culture of isolated follicles. Different stage follicles were
      cultured in the presence or absence of frog pituitary homogenate (FPH, 0.1
      pituitary/2 ml) and/or various steroid precursors (25-200 ng/2 ml). Amounts of
      E2, T, androstenedione (AD), 17 alpha-hydroxyprogesterone (17 alpha-OHP4), or P4
      secreted into the medium were measured by RIA. Exogenous pregnenolone (P5) was
      converted to P4 by all types of follicles in a dose-dependent manner in the
      absence of FPH. Addition of FPH markedly enhanced medium levels of P4 in all
      sized follicles. Highest levels of P4 were presented in cultures containing the
      largest follicles. Such follicles were much less efficient than intermediate
      follicles in metabolizing P4 to AD or T. FPH suppressed conversion of exogenous
      17 alpha-OHP4 but not androstenedione to testosterone by the largest follicles.
      Exogenous T was converted to E2 only by medium-sized follicles and FPH had little
      or no stimulating or inhibiting effect on this process in either medium- or
      intermediate-sized follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282173
TI  - Salmonid pituitary gonadotrophs. III. Chronological appearance of GTH I and other
      adenohypophysial hormones in the pituitary of the developing rainbow trout
      (Oncorhynchus mykiss irideus).
AB  - The first appearance of adenohypophysial cells in the developing rainbow trout
      embryo was studied by immunocytochemistry. Antibodies generated against the beta
      subunits of coho salmon gonadotropins (GTH I and GTH II), the beta subunit of
      human thyroid stimulating hormone (TSH), chum salmon prolactin (PRL), chum salmon
      growth hormone (GH), and synthetic alpha-MSH were used as immunocytochemical
      probes. The pituitary anlage was first recognized at developmental stage 21 (18
      days postfertilization). At this stage, immunoreactive (ir) PRL and alpha-MSH
      cells were identified in the rostral and caudal regions of the pituitary,
      respectively. Cells containing ir-GH and ir-adrenocorticotropin (ACTH) appeared
      at stage 28 (35 days postfertilization). At the last stage before hatching (stage
      29, 42 days postfertilization) ir-TSH cells were identified. Ir-GTH I cells were
      first observed in the pituitary at stage 32 (15 days after hatching), when
      mitosis of gonadal germ cells also was observed. At stage 35 (35 days after
      hatching), meiotic figures were first observed in a few germ cells of some fish
      indicating that gonadal sex differentiation probably begins at about this time.
      Cells containing ir-GTH II were not apparent in the pituitary at any stage of
      embryonic or larval development (up to stage 35) and were not present in
      pituitaries of trout at 6 months of age when the ovaries were in the
      perinucleolus stage and when only spermatogonia, but no spermatocytes were
      present in the testis. These observations suggest that GTH I, but not GTH II, may
      regulate initial gonadal growth and development in the embryonic and larval
      rainbow trout.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282174
TI  - Photoperiodic regulation of follicle-stimulating hormone binding to gonads and of
      plasma gonadotropin concentrations in Indian weaver birds.
AB  - Previous studies showed that changes of gonadal weight and of follicle
      stimulating hormone (FSH) receptor number in response to fluctuations in natural
      environmental conditions are smaller in female than in male Indian weaver bird
      (Ploceus phillippinus). Therefore, we studied whether the response to artificial
      photoperiodic changes differs between the sexes. Birds were transferred to short
      day (SD) photoperiods during the breeding phase (June). Other birds were
      subjected to long-day (LD) photoperiods during the nonbreeding phase (December).
      Exposure to SD for 10 weeks induced a marked testicular weight decrease.
      Similarly, FSH binding per unit testicular weight as well as per two testes
      decreased after SD exposure. The influence of photoperiodic manipulations on the
      ovarian weight was much smaller than that on the testicular weight. SD exposure
      did not alter FSH binding either per unit ovarian weight or per ovary. Plasma
      gonadotropin concentration significantly decreased in both sexes subjected to SD
      environment. On the other hand, exposure to LD significantly increased testicular
      weight. LD exposure slightly increased ovarian weight, but the increase was
      statistically not significant. FSH binding per unit testicular weight markedly
      increased 10 weeks after transfer to LD. The total FSH binding per two testes
      showed a parallel change with the testicular weight. However, there was no
      significant increase in FSH binding per unit ovarian weight during 10 weeks of LD
      exposure. Although LD exposure for 10 weeks significantly increased the total FSH
      binding per ovary, the rate of increase was much smaller than that in the testes.
      The plasma gonadotropin level in both sexes was increased by LD exposure.
      Scatchard plot analyses of FSH binding indicated that FSH binding changes were
      due to changes in binding site number. These results suggest that photoperiod
      regulates FSH receptor numbers particularly in the testis. Such an effect is
      manifested by marked changes in the testicular weight under different
      photoperiodic conditions in the subtropical bird.

PMID- 8282175
TI  - Chemical identification of the mammalian oxytocin in a holocephalian fish, the
      ratfish (Hydrolagus colliei).
AB  - The neurohypophysial hormones of the ratfish (Hydrolagus colliei), a species
      belonging to the subclass Holocephali of cartilaginous fishes, have been
      investigated. An oxytocin-like hormone has been isolated from acetone-desiccated
      pituitary glands by using successively molecular sieving and high-pressure liquid
      chromatography. The peptide has been identified as oxytocin by coelution with
      synthetic oxytocin in HPLC, amino acid sequencing, mass spectrometry, and C
      terminal sequencing through carboxypeptidase Y. Vasotocin may be present in a
      very small amount. Cartilaginous fishes appear to display a great diversity in
      their oxytocin-like hormones since five different peptides have been identified
      in rays and sharks that belong to the second subclass Selachii.

PMID- 8282176
TI  - Effect of photoperiod on gonadal maintenance and development in the marsh rice
      rat (Oryzomys palustris).
AB  - Reproductive responsiveness to photoperiod was examined in adult and prepubertal
      rice rats. In Experiment 1, adult males on 16L:8D and 14L:10D maintained
      testicular size, while exposure to 12L:12D and 10L:14D resulted in testicular
      regression, followed by spontaneous testicular recrudescence. Adult females
      (Experiment 2) on long photoperiods had larger uterine and ovarian weights at
      most times examined and maintained vaginal patency compared to females on short
      photoperiods. Reproductive development of male rice rats (Experiment 3) was
      stimulated on 16L:8D and 14L:10D with rapid testicular development occurring by
      12 weeks of age, while in males reared on 12L:12D and 10L:14D reproductive
      development proceeded slowly and was completed at approximately 26 weeks of age.
      Females on 16L:8D and 14L:10D experienced rapid uterine development compared to
      those on 12L:12D and 10L:14D. Ovarian weights on 14L:10D were significantly
      greater than ovarian weights on 12L:12D. Finally, vaginal patency was attained
      more rapidly on 16L:8D than on 14L:10D and was markedly inhibited on 12L:12D and
      10L:14D. These data show that reproduction in adult male and female rice rats is
      regulated, at least in part, by photoperiod and that reproductive development in
      juveniles is also under photoperiodic control.

PMID- 8282177
TI  - Divergence of gene expression in neurohypophysial hormone precursors among
      salmonids.
AB  - Salmonid fish have pairs of genes for various hypothalamic and pituitary hormones
      including neurohypophysial hormones, vasotocin, and isotocin, probably because
      they are tetraploid. The problem here is whether two genes for the same hormone
      are expressed equally or differently. We therefore examined expression patterns
      of vasotocin and isotocin genes in four salmonid species using Northern blot
      analysis with chum salmon cDNAs as hybridization probes. The presence of two
      vasotocin and also two isotocin genes was confirmed by Southern blot analysis in
      rainbow trout and sockeye salmon which were not examined previously. Prior to
      Northern blot analysis, isotocin-I cDNA of sockeye salmon was determined and
      compared to those of chum salmon and masu salmon, since molecular probes are so
      specific that cross-species hybridization often leads misinterpretation in a
      quantitative study. The nucleotide sequence of sockeye salmon isotocin-I cDNA
      showed sufficiently high homology (> 96.0%) to those of chum salmon and masu
      salmon for cross-species hybridization among salmonids. Northern blot analysis
      showed that both isotocin-I and isotocin-II genes were well expressed in all
      species examined. Expression of isotocin-I gene tended to be relatively higher
      than that of isotocin-II gene in all species. However, expression pattern of
      vasotocin-I and vasotocin-II genes did not coincide among species. Expression of
      vasotocin-II genes was very weak or scarce in masu salmon and rainbow trout,
      while that in sockeye salmon was stronger than vasotocin-I gene expression. The
      present result may reflect complicated molecular evolution of salmonid vasotocin
      genes probably both in regulatory and coding regions.

PMID- 8282178
TI  - Isolation and sequencing of deer and sheep insulin-like growth factors-I and -II.
AB  - We have developed a simple method for the isolation of highly purified cervine
      (c) and ovine (o) insulin-like growth factors-I (IGF-I) and -II. The IGFs were
      isolated from acidified serum by cation exchange chromatography and then purified
      by gel filtration, chromatofocusing, and reverse-phase chromatography. The IGF
      preparations are > 95% pure. The cIGF-I preparation contains < 0.056% cIGF-II and
      the oIGF-I preparation contains < 0.01% oIGF-II. Both the IGF-II preparations
      contain < 0.01% IGF-I. The amino acid sequence of cIGF-I has two differences when
      compared with human (h) IGF-I. The cIGF-II sequence, which is identical to bovine
      IGF-II, has three differences when compared with hIGF-II.

PMID- 8282179
TI  - Brain content of cGnRH I and II during embryonic development in chickens.
AB  - We used specific radioimmunoassays to measure chicken gonadotropin-releasing
      hormones I and II (cGnRH I and II) in extracts of chicken brain as a first step
      in determining whether these peptides may function identically during embryonic
      development in birds. In three experiments chicken embryo brains were removed at
      various times between Day 6 of incubation and hatching. In Experiment 3, the sex
      of embryos was identified by means of polymerase chain reaction amplification of
      a W chromosome-specific DNA sequence. Brain concentrations of cGnRH I increased
      sharply from Day 6 of incubation to Day 8, then decreased until Day 10 to Day 12,
      followed by an increase beginning on approximately Day 17 and continuing until
      hatch. In contrast, cGnRH II concentration remained low until about Day 14 of
      incubation, then increased progressively until, at hatch, brain content of cGnRH
      II was approximately 9 to 11 times that of cGnRH I. The difference in development
      pattern and total content of these peptides supports the view that any
      physiologic function they may have might be differentiated as early as Day 7 of
      incubation.

PMID- 8282180
TI  - Role of cortisol in hypoosmoregulation in larvae of the tilapia (Oreochromis
      mossambicus).
AB  - The total cortisol content in tilapia was 55 pg immediately following
      fertilization, then decreased abruptly and maintained a lower level of 10-20 pg
      until hatching; after hatching the cortisol content increased to 50 pg by the 7th
      day. Fertilized eggs were incubated in either 32% saltwater or fresh water and
      sampled at various developmental stages. Both groups showed dramatic changes in
      cortisol content following development. However, no significant difference in the
      cortisol level was found between the two groups. Tilapia larvae, hatched in fresh
      water, were reared with feed containing 0 (control) or 150 mg/kg wt/day cortisol,
      corticosterone, 17 alpha-hydroxyprogesterone (17 alpha-OHP) or 11 alpha
      deoxycortisol (11 alpha-DC) for 8 days and then transferred directly to 27.5%
      saltwater. Those reared with corticosterone, 17 alpha-OHP, or 11 alpha-DC,
      similar to the control, all died within 4-8 hr after the transfer. However, the
      larvae treated with cortisol showed a much higher survival rate of 40-60%. The
      tissue osmolality in the control larvae, 394.3 +/- 3.7 (mmol/kg), increased
      abruptly after transfer to 26% saltwater and reach a peak, 681.5 +/- 47.5, before
      the larvae all died (12th hr after the transfer). In contrast, tissue osmolality
      in cortisol-treated (150 mg/kg wt/day for 12 days) larvae was 570.7 +/- 62.6 at
      the 12th hr and then began to decrease to 448.5 +/- 9.4 at the 24th hr and 386.0
      at the 48th hr. These findings suggest that cortisol could play a critical role
      in the hypoosmoregulation in tilapia larvae.

PMID- 8282181
TI  - Streptomyces lividans as host for heterologous protein production.
AB  - Streptomycetes are Gram-positive soil bacteria with a well differentiated
      morphology. They are considered interesting candidates for the production of
      heterologous proteins for several reasons, including their efficient secretion
      mechanism by which the secreted proteins are localized into the culture
      supernatant. In view of this potential, this review article describes different
      aspects of gene expression and regulation in Streptomyces, and summarizes and
      discusses results obtained using Streptomyces lividans as host for secretion of
      heterologous proteins of prokaryotic and eukaryotic origin.

PMID- 8282182
TI  - Identification and cloning of a cyclic beta-(1-->3), beta-(1-->6)-D-glucan
      synthesis locus from Bradyrhizobium japonicum.
AB  - A cosmid clone complementing a cyclic beta-(1-->2)-glucan biosynthesis (ndvB)
      mutant of Rhizobium meliloti was isolated from a Bradyrhizobium japonicum gene
      library. This clone specified synthesis of beta-(1-->3), beta-(1-->6)-linked
      glucans in R. meliloti. The complemented strain was osmotically tolerant and
      symbiotically competent on alfalfa. Thus, beta-(1-->3), beta-(1-->6)-glucans can
      substitute functionally for beta-(1-->2)-glucans in R. meliloti.

PMID- 8282183
TI  - The adenylate cyclase catalytic domain of Streptomyces coelicolor is carboxy
      terminal.
AB  - A DNA fragment of Streptomyces coelicolor encoding the carboxy-terminal catalytic
      domain of adenylate cyclase was cloned, sequenced and expressed in an Escherichia
      coli cya-defective strain where it produced nanomole levels of cAMP. The amino
      acid sequence of the enzyme displays similarities with the Brevibacterium
      liquefaciens pyruvate regulated adenylate cyclase.

PMID- 8282184
TI  - Genomic fingerprinting of Clostridium difficile isolates by using a random
      amplified polymorphic DNA (RAPD) assay.
AB  - This study describes the use of a new and easy method called random amplified
      polymorphic DNA (RAPD) assay to distinguish strains of C. difficile. We used two
      single short primers (AP4 and AP5) with arbitrary nucleotide sequences in a
      polymerase chain reaction to amplify genomic DNA. The profiles observed after
      electrophoretic separation were able to distinguish 20 reference C. difficile
      strains previously serotyped by Delmee's method. The fingerprints of 11
      epidemiologically unrelated C. difficile strains clearly yielded a DNA
      polymorphism between all the strains. Latterly, RAPD profiles of 11 C. difficile
      strains isolated from 2 independent suspected outbreaks showed, in each case, a
      predominant banding pattern corresponding to an epidemic strain. These results
      suggest that RAPD assay could be a valuable tool for epidemiological studies.

PMID- 8282185
TI  - Rapid and sensitive method for detection of Salmonella strains using a
      combination of polymerase chain reaction and reverse dot-blot hybridization.
AB  - We have developed a reverse dot-blot hybridization assay for detection of
      Salmonella using Salmonella-specific oligonucleotide probes designed from the
      base sequence of the 16S rRNA gene (rDNA). The target fragment of 16S rDNA was
      amplified, and labelled with biotin by the polymerase chain reaction. The
      amplified fragment was hybridized with the membrane-immobilized probe and the
      hybridization was detected by chemiluminescence. Amplified fragments from 24
      different serovars of Salmonella hybridized with the probes, whereas those of
      species of Enterobacteriaceae, Pseudomonas aeruginosa, Bacillus subtilis, and
      Staphylococcus aureus failed to hybridize. By this assay, it was possible to
      detect in the order of 10(4) bacteria in fish meat homogenate in 10 h.

PMID- 8282186
TI  - Strong and regulated promoters in the cyanobacterium Anabaena PCC 7120.
AB  - The strengths of several promoters were assessed in the cyanobacterium Anabaena
      PCC 7120 by fusing them to luxAB, encoding bacterial luciferase. Two promoters,
      Ptac and PpsbA, with sequences nearly identical to consensus Escherichia coli
      sigma 70 promoters, gave as high or higher expression than the strong Anabaena
      promoter, Prbc. Pnpt, the natural promoter driving expression of the kanamycin
      resistance determinant from Tn5, was poorly expressed in Anabaena. The Lac
      repressor partially repressed expression from Ptac, permitting regulated
      expression in Anabaena after induction with isopropyl thiogalactoside to a level
      4-5-fold higher than without inducer.

PMID- 8282187
TI  - Role of the fixGHI region of Azorhizobium caulinodans in free-living and
      symbiotic nitrogen fixation.
AB  - A 19-kb DNA region containing genes sharing homology with Rhizobium meliloti
      fixNOQP and fixGHI was isolated from a genomic library of Azorhizobium
      caulinodans. Identity of fixG was confirmed by partial nucleotide sequencing.
      Mutant strains in the fixGHI region were constructed by deletion or Tn5
      insertions. In contrast with the situation in R. meliloti, the mutants still
      displayed a significant nitrogenase activity in symbiosis.

PMID- 8282188
TI  - Genetic analysis of the regulatory putP region (coding for proline permease) in
      Klebsiella pneumoniae M5a1: evidence for regulation by the nac system.
AB  - During a search for nitrogen-controlled promoters on the Klebsiella pneumoniae
      M5a1 chromosome, the regulatory region of putP (coding for proline permease) was
      cloned, sequenced and analyzed. The region contained a weak sigma 70-dependent
      promoter and putative binding sites for the cAMP-CAP complex and the Nac
      regulatory protein, the latter probably providing a link with the nitrogen
      regulation (Ntr) system. Using a lacZ gene fusion, evidence for control of putP
      transcription by both Nac and Ntr was obtained.

PMID- 8282189
TI  - Purification of aspartate transcarbamoylase from Pseudomonas syringae.
AB  - The aspartate transcarbamoylase (ATCase) from Pseudomonas syringae has been
      purified. The purified enzyme was shown by SDS-PAGE to give two bands.
      Unambiguous results from N-terminal sequencing suggested that each band
      represented a homogeneous polypeptide. The M(r) (relative molecular mass) of the
      polypeptides was estimated to be 47 kDa and 34 kDa. The M(r) of the holoenzyme
      determined by gel filtration and electrophoretic migration in polyacrylamide
      gradient gels under non-denaturing conditions was estimated at approximately 490
      kDa. These findings suggest a subunit structure different from any previously
      described for a bacterial ATCase.

PMID- 8282190
TI  - In vitro assay for the Bacillus subtilis signal peptidase SipS: systems for
      efficient in vitro transcription-translation and processing of precursors of
      secreted proteins.
AB  - The signal peptidase (SPase) SipS of Bacillus subtilis is responsible for the
      processing of precursors of secreted proteins. It differs from the SPases of Gram
      negative bacteria in structure and specificity. To assay the activity of SipS in
      vitro, two efficient transcription-translation systems for the synthesis of radio
      labelled precursors were developed. The systems were completely derived from B.
      subtilis. Post-translational in vitro processing of pre-staphylokinase by SipS
      was demonstrated. SipS activity was stimulated in vitro by several non-ionic
      detergents, whereas it was not affected by a large variety of proteinase
      inhibitors. SipS shares the latter property with other SPases.

PMID- 8282191
TI  - Comparison of the conserved region in the dnaA gene from three mollicute species.
AB  - Polymerase chain reaction was carried out to amplify the conserved region (789 bp
      in the case of Mycoplasma capricolum) of the dnaA gene (1350 bp in the case of M.
      capricolum) of 15 representatives of the class Mollicutes using degenerate
      oligonucleotide primers. The dnaA gene fragments were amplified from M. mycoides
      subsp. capri, Spiroplasma apis and S. citri. The amino acid sequences deduced
      from the nucleotide sequences of the amplified fragments showed very low
      similarities to those of the corresponding regions of four walled bacteria. The
      values of similarity between any two of the three mollicute species were lower
      than those between any two of the four walled bacteria.

PMID- 8282192
TI  - Molecular characterization of the p100 gene of Borrelia burgdorferi strain PKo.
AB  - The p100 gene coding for the p100 protein of Borrelia burgdorferi strain PKo has
      been cloned, sequenced and expressed in Escherichia coli. An open reading frame
      including upstream and downstream sequences with potential translation and
      transcription signals could be identified. The reading frame consists of 1989
      nucleotides corresponding to a protein of 663 amino acids and a calculated
      molecular mass of 75.8 kDa. The protein has a leader peptide and is processed
      without modification at the N-terminus. A high percentage of amino acid sequence
      identity could be found to the high-molecular mass protein p83/p93 of B.
      burgdorferi strain B31.

PMID- 8282193
TI  - Transgenic mice and transhybridomas producing chimeric mouse/human anti-human
      interleukin-2 receptor recombinant antibodies.
AB  - Transgenic mice were developed that secreted chimeric mouse/human anti-human
      interleukin-2 receptor (IL-2R) antibodies (Ab) into their serum. In addition,
      hybridomas producing the chimeric Ab in tissue culture were generated from the
      transgenic mice. The presence of the mouse/human immunoglobulin (Ig) transgene
      did not appear to affect rearrangement of endogenous murine Ig in the hybridomas.
      Serum levels of the chimeric Ab correlated with transgene copy number. Although
      many of the transgenic lineages had serum titers of the chimeric Ab comparable to
      endogenous mouse IgG, there was no apparent correlation with endogenous mouse IgG
      levels.

PMID- 8282194
TI  - A genetic selection elucidates structural determinants of arginine versus lysine
      specificity in trypsin.
AB  - A genetic selection has been used to isolate variants of the serine protease,
      trypsin (Tsn), altered in specificity toward lysine- and arginine-containing
      substrates. Growth of a lysine auxotroph of Escherichia coli was coupled to
      activation by Tsn of a non-nutritive source of lysine present in selective media.
      Nine Tsn variants possessing partial activities were isolated from a random
      library encompassing amino acids 189 and 190 at the base of the primary
      specificity pocket. Functional analysis of these isolates indicates that
      preservation of activity toward lysine-containing substrates is more tolerant to
      mutation than is activity toward equivalent arginine-containing substrates. Both
      the position, as well as the accessibility to substrate, of a negatively charged
      group in the binding pocket appear critical to maintenance of high-level
      catalytic potency by Tsn.

PMID- 8282195
TI  - Computer-assisted drug discovery--a review.
AB  - A structure-based approach to new drug development is an attractive alternative
      to the traditional paradigm of drug discovery through screening. The elements of
      this approach are reviewed, with emphasis on the use of homology-built model
      structures. Two examples, proteases from the organisms that cause malaria and
      schistosomiasis, illustrate both the model-building process and the feasibility
      of using such models to computationally screen and identify compounds that
      inhibit their targets in the low micromolar range.

PMID- 8282196
TI  - Discovery of D-amino-acid-containing ligands with selectide technology.
AB  - When all L-amino acid (aa) random peptide libraries synthesized on solid-phase
      particles were screened (Selectide Technology), we identified several peptide
      ligands (YG_F_) that interacted specifically with an anti-beta-endorphin
      monoclonal antibody (clone 3E7) (single-letter aa symbols; symbols '_' indicate
      variable aa). Here, we report on the screening of three different D-aa-containing
      pentapeptide libraries (XxXxX, xXxXx and xxxxx, wherein X = L-aa, and x = D-aa)
      with the same antibody, in which several D-aa-containing ligands were identified.
      The binding affinities of many of these D-aa-containing ligands were as least two
      orders of magnitude lower than that of YGGFL, for which the Ki is 17.5 nM.

PMID- 8282197
TI  - Dicistronic selection for nuclear proteins in living animal cells.
AB  - We present an expression/selection system designed for the purification of cell
      lines inducibly expressing genes coding for unselectable proteins by using
      dicistronic selection for the cell surface marker CD4. This system enabled us to
      establish and purify c-myb expressing variants of the v-myb transformed chicken
      monoblast cell line BM2 with high efficiency.

PMID- 8282198
TI  - The discovery and characterization of a novel nucleotide-based thrombin
      inhibitor.
AB  - Thrombin is a serine protease that plays a pivotal role in thrombosis and
      hemostasis, and is a major target for anticoagulation and cardiovascular disease
      therapy. Using a novel in vitro selection/amplification technique, we have
      identified a new class of thrombin inhibitors based on single-stranded DNA
      (ssDNA) oligodeoxyribonucleotides (oligos). These thrombin inhibitors are the
      first example of the use of this technique to obtain ssDNA oligos that bind a
      target protein that does not interact physiologically with nucleic acid. Here, we
      review how iterative selection and amplification were used to identify short
      ssDNA sequences that bind and inhibit thrombin (Bock et al., Nature 355 (1992)
      564-566), and the tertiary structure of one aptamer sequence (Wang et al.,
      Biochemistry 32 (1993) 1899-1904). Results from in vitro and in vivo studies are
      also summarized (Griffin et al., Blood 81 (1993) 3271-3276). The discovery of a
      new class of thrombin inhibitors using this technology demonstrates the power of
      this new approach for rapid drug discovery and development.

PMID- 8282199
TI  - Selection of new biologically active molecules from random nucleotide sequences.
AB  - Genetic diversity can be achieved in vitro by inserting random nucleotide (nt)
      sequences into cloned genes. In the case of enzymes, subsequent genetic
      complementation can be used to select for new mutants that exhibit different
      substrate specificities, altered catalytic activities, or altered temperature
      sensitivities. Using this technique, one can also analyze the contribution of
      different amino acid residues to the structure and function of enzyme. Selecting
      biologically active DNA sequences from large random populations provides a new
      method for identifying nt sequences with unique functions. Analogous random
      sequence selection techniques have been applied to determine the consensus
      sequence of the Escherichia coli promoters, DNA and RNA sequences that bind
      specific protein(s), DNA regulatory sequences, ribozyme(s) and ligand-specific
      RNA(s). In this manuscript, we will consider recent data obtained in our
      laboratory as a result of inserting random sequences into the putative nucleoside
      binding site of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK). We
      have obtained over 2000 new mutant HSV-1 TKs, some of which are stable at higher
      temperatures or have altered substrate specificity and/or catalytic rates when
      compared to those of the wild-type enzyme.

PMID- 8282200
TI  - Peptidomimetics of the immunoglobulin supergene family--a review.
AB  - An important goal of structural biochemistry is the reduction of complex
      molecules to small functional units that are amenable to high-resolution
      structural analysis and rapid modification. The dissection of multidomain
      proteins into small synthetic conformationally restricted components is an
      important step in the design of low-molecular-weight nonpeptides that mimic the
      activity of the native protein. Mimetics of critical functional domains might
      possess beneficial properties in comparison to the intact proteinaceous species
      with regard to specificity and therapeutic potential, and are valuable probes for
      the study of molecular recognition events.

PMID- 8282201
TI  - Selection of human anti-hapten antibodies from semisynthetic libraries.
AB  - Semisynthetic human Fab libraries were constructed, displayed on the surface of
      filamentous phage and selected for binding to three hapten conjugates. A number
      of Fabs were isolated and characterized with respect to affinity and specificity.
      Fabs exhibited affinities of between 80 and 29 nM, as determined by surface
      plasmon resonance, for the conjugate on which they were selected. Conservation of
      Asp101 in the third heavy-chain complementarity determining region (HCDR3)
      appears to be important in the construction of synthetically diverse repertoires.

PMID- 8282202
TI  - Display of biologically active proteins on the surface of filamentous phages: a
      cDNA cloning system for selection of functional gene products linked to the
      genetic information responsible for their production.
AB  - A cloning and expression system allowing display of functional cDNAs or other
      gene products on the surface of filamentous phage has been developed, exploiting
      the high-affinity interaction of the Jun and Fos leucine zippers. Gene jun was
      expressed from a lacZ promoter as a fusion protein with the viral coat protein,
      pIII, thereby being structurally incorporated into phage particles during
      infection with a helper phage. Using a second lacZ promoter of the phagemid, gene
      fos was co-expressed as an N-terminal fusion peptide to cDNA library gene
      products, so that the resulting Fos-fusion proteins could become associated with
      the Jun-decorated phage particles. To avoid interphage exchange of fos-cDNA
      fusion products, cysteines were engineered at the N- and C-termini of each of the
      leucine zippers, providing a covalent link of the cDNA gene product to the
      genetic instructions required for its production. Dissociation between phage and
      cDNA gene products was readily achieved using reducing agents. Phages displaying
      gene products covalently anchored on their surface via the modified leucine
      zippers can be selectively enriched 10(4)-10(6)-fold over nonspecific phages
      using antibodies. Thus, this cloning system allows rapid isolation of rare mRNA
      products from complex cDNA libraries by enrichment with appropriate ligands. This
      approach should allow the expression and cloning of dimeric proteins by cDNA
      shuffling.

PMID- 8282203
TI  - The broad utility of soluble peptide libraries for drug discovery.
AB  - The use of soluble peptide combinatorial libraries made up of millions, billions,
      or now even trillions (10(6), 10(9) and 10(12)) of peptides, currently used in a
      wide range of investigations, is discussed. These include: antibody/peptide
      antigen studies, the development of new ligands through the use of radio receptor
      assays, novel enzyme inhibitors, antibacterial and antifungal peptides through
      the use of microdilution assays, antivirals in plaque assays, and cardiovascular
      drugs in in vivo studies. The use of a new positional scanning library composed
      of approximately four trillion decapeptides is illustrated in a radio receptor
      assay. The criteria by which libraries, in general, can be judged will be
      described.

PMID- 8282204
TI  - Cloning in a bacteriophage lambda vector for the display of binding proteins on
      filamentous phage.
AB  - We have combined the efficiency and ease of use of bacteriophage lambda vectors
      with the power of phage display screening technology to create SurfZAP. The use
      of bacteriophage lambda allows the construction of large lambda expression
      libraries, which are rapidly and efficiently converted to stable plasmid
      libraries by mass excision. In SurfZAP, clones are expressed as fusions with
      amino acids 198-406 of the M13 minor coat protein (cpIII) and are displayed on
      the surface of filamentous phage. When produced with helper phage proteins, the
      fusion proteins are incorporated into the surface of phagemid particles. We
      demonstrate the utility of biopanning by isolating tetanus toxoid-binding mouse
      Fab clones from SurfZAP libraries. Approximately 10-100-fold enrichment of
      specific clones was observed after each panning round. The ability to create a
      large library of genotypes and screen the phenotypes by activity may be a potent
      methodology for basic research and drug discovery.

PMID- 8282205
TI  - CBC: is it needed in assessing preop risk?

PMID- 8282206
TI  - NSAIDs for elderly: a list of side effects.

PMID- 8282207
TI  - Making geriatric assessment an asset to your primary care practice.
AB  - Geriatric assessment provides the physician with an individualized care plan for
      at-risk older patients with complex health problems. Its four basic components
      are physical, mental, functional, and social/economic health. Although the ideal
      assessment is performed by a team from a variety of disciplines, primary care
      physicians may perform a limited version in the office and then make appropriate
      referrals for further evaluation. Various screening instruments are helpful, but
      they have their limitations. Results provide you with a blueprint that aims to
      restore function, lower costs, and improve the patient's quality of life.

PMID- 8282208
TI  - Vascular dementia: an updated approach to patient management. A roundtable
      discussion: Part 3.
AB  - A new clinical approach to the prevention and treatment of vascular dementia is
      evolving. The physician has numerous options to consider when the patient is in
      an asymptomatic "brain-at-risk" stage. These include treatment of hypertension,
      elevated cholesterol, and atrial fibrillation, as well as smoking cessation,
      exercise, and dietary changes. When there are early signs of cerebrovascular
      disease, such as TIAs and subtle cognitive changes, more aggressive therapy may
      be warranted, including carotid endarterectomy, anticoagulants, aspirin, and
      ticlopidine. For patients with vascular dementia, treatment focuses on preventing
      further cerebrovascular damage and managing related symptoms, such as depression.

PMID- 8282209
TI  - Fighting influenza: stronger vaccines are researchers' goal.

PMID- 8282210
TI  - Reactions of active oxygen and nitrogen species studied by EPR and spin trapping.
AB  - The reactions of hydrogen peroxide (H2O2) with nitrite (NO2-) and of superoxide
      (O2-.) with nitric oxide (NO.) were studied using EPR and spin trapping
      techniques. These reactions reportedly have a common peroxynitrite (OONO-)
      intermediate. It has been suggested that this intermediate when protonated
      rapidly decomposes producing hydroxyl radicals (.OH) and the nitrogen dioxide
      radical (NO2.). The production of .OH in the reaction between H2O2 and NO2- was
      confirmed in spin trapping experiments using the spin trap 5,5-dimethyl-1
      pyrroline-1-oxide (DMPO). H2O2 and NO2- were mixed at neutral pH and then the pH
      was decreased to pH 3-3.5 in the presence of DMPO or DMPO and ethanol. In these
      experiments, the EPR spectrum of the DMPO-OH adduct was obtained in addition to a
      weak EPR spectrum consisting of a triplet of triplets (a N = 1.415 mT and a N
      beta = 0.35 mT) indicating the addition of a nitrogen centered radical to DMPO.
      The formation of .OH was confirmed using ethanol as an .OH scavenger. The DMPO
      hydroxyethyl adduct was produced from the reaction of .OH with ethanol. However,
      in experiments using an excess of ethanol, the formation of DMPO-OH was not
      prevented. This suggests that the DMPO-OH formed in the decomposition of HOONO
      does not entirely originate from a direct addition of .OH to DMPO. The reaction
      of O2-. with NO. was carried out in deaerated and air-saturated solutions at pH
      12.3 where the dismutation of O2-. is minimal. The pH was then decreased to pH 3
      3.5 in the presence of DMPO or DMPO and ethanol. In these experiments, the most
      prominent EPR spectrum obtained was a triplet of triplets (aN = 1.415 mT and a
      beta N = 0.35 mT) suggesting the addition of a nitrogen centered radical to DMPO.
      The formation of DMPO-OH was minimal and there was no formation of DMPO
      hydroxyethyl adducts in the presence of ethanol. The results suggest that NO. in
      solution yields additional reactive species which act as nitrating agents in the
      presence of DMPO.

PMID- 8282211
TI  - 3rd international symposium on spin trapping and aminoxyl radical chemistry.
      Kyoto, Japan, 22-24 November 1991. Proceedings.

PMID- 8282212
TI  - Antioxidant properties of antiulcer Kampo medicines.
AB  - Kampo medicines, aqueous extracts of a mixture of natural crude drugs, have
      numerous ingredients. Recent pharmacologic studies on Kampo medicines have
      clarified their many and varied biological activities. In this study, based on
      recent research that has been directed toward the excellent antioxidant
      properties of Kampo medicines, we investigated antioxidant activities of three
      Kampo medicines (TJ-10, TJ-35, TJ-43), which are clinically used for gastritis or
      peptic ulcer, by the electron paramagnetic resonance (EPR) spin trapping method.
      These Kampo medicines, especially TJ-35 scavenged superoxide generated from the
      hypoxanthine-xanthine oxidase system, and slightly inhibited the superoxide
      generation from polymorphonuclear leukocytes stimulated by phorbol myristate
      acetate or opsonized zymosan. Three Kampo medicines, especially TJ-35 also
      inhibited the generation of hydroxyl radicals by the Fenton reaction. These
      results suggest that these antioxidant properties may be partly responsible for
      anti-ulcer actions of these three Kampo medicines, especially TJ-35.

PMID- 8282213
TI  - Detection of specific base sequences in solution using DNA probes labeled with d-
      and/or 15N-substituted spin-labels.
AB  - In order to enhance the sensitivity and the accuracy of the detection by the DNA
      probe method in which spin-labeled oligonucleotides are used as probes, 4-amino
      2,2,6,6-tetramethylpiperidine-15N-oxyl-d16 (4-amino-TEMPO-15N-d16) and 4-amino
      2,2,6,6-tetramethylpiperidine-14N-oxyl-d16 (4-amino-TEMPO-14N-d16) were
      incorporated into the phosphate linkage of oligonucleotides by the hydrogen
      phosphonate method and these DNA probes were used for the detection of target
      DNAs in solution. The intensities of the electron paramagnetic resonance (EPR)
      signals of the oligonucleotides labeled with 4-amino-TEMPO-14N-d16 and 4-amino
      TEMPO-15N-d16 were 3-fold and 4-fold larger than that of the oligonucleotide
      labeled with 4-amino-TEMPO-14N, respectively. Also, the EPR lines of these
      labeled oligonucleotides do not overlap each other, allowing the detection of two
      different regions in the same target DNA by the single EPR measurement.

PMID- 8282214
TI  - Oligonucleotides site-specifically spin-labeled at 5'-terminal or internucleotide
      linkage and their use in gene analyses.
AB  - Spin-labeled oligonucleotides (S-probes) were synthesized and examined as DNA
      probes to monitor hybrid formation. TEMPO was introduced either at the
      internucleotide linkage of 5'-terminus (Type 1) or at the 5'-terminal hydroxyl
      group (Type 2) and both types of S-probes were used in this study. The presence
      of target DNA was detected in solution by EPR spectroscopy for both types of S
      probes. Hybridization of the S-probes resulted in notable broadening of EPR line
      width, accompanied by a decrease in the EPR signal height ratio for I(-1)/I(0).I(
      1)/I(0) of S-probes having no spacer between oligonucleotide and TEMPO decreased
      more markedly than that of S-probes with a spacer, indicating that TEMPO should
      be introduced to an oligonucleotide directly to monitor hybrid formation. When
      M13mp8 single-stranded DNA with or without an EcoRI recognition site was selected
      as a target DNA, hybrid formation was detected only for DNA containing EcoRI site
      in solution using spin-labeled oligonucleotides.

PMID- 8282215
TI  - The reactions of 3,5-dibromo-4-nitrosobenzenesulfonate and its biological
      applications.
AB  - Recently, 5,5-dibromo-4-nitrosobenzenesulfonate (DBNBS) has been applied to
      detect biological free radicals. However, DBNBS has various non-specific
      reactions which lead to preplexing results. Thus, we investigated some basic
      reactions of DBNBS in combination of other nitroso spin traps to assign DBNBS
      spin adducts derived from human platelets which presumably related to the
      endothelium-derived relaxing factor (EDRF). The collagen activated platelets
      yielded four spin adducts (ST, LT, SS, and LS) in the presence of DBNBS (40 mM).
      The broad triplet due to ST was also observed by bubbling NO gas into a DBNBS
      solution. To identify ST, nitrosobenzene (NB) in dry dioxane was mixed with NO
      saturated dioxane. The NB-NO spin adduct was observed but decomposed into
      diphenyl aminoxyl by the addition of H2O indicating that the primary adduct
      formed by the reaction of NO and DBNBS is unstable and turns into a dimerization
      product. Although ST could be eliminated by the inhibitor of EDRF, ST was shown
      to be produced by non-specific reactions. Another triplet was assigned to an S
      centered radical because thiyl radicals which were generated from either the
      decomposition of S-nitrosothiol, or glutathione oxidation exhibited almost
      identical triplet signals. The other two sextets were assigned to C-centered
      radical adducts. Thus, DBNBS detected NQ-related, S-centered, and two C-centered
      radicals derived from human platelets. Special cautions are necessary for the
      identification of DBNBS spin adducts in a biological system to exclude
      artifactual radicals.

PMID- 8282216
TI  - Tert-butylhydroperoxide bioactivation to methyl radical in rat liver mitochondria
      and submitochondrial particles.
AB  - Electron paramagnetic resonance spectroscopy (EPR) coupled to the spin trapping
      technique was used to detect carbon-centered radicals in rat liver mitochondria
      and submitochondrial particles exposed to t-butyl-hydroperoxide (TBH), using the
      spin trapping agent 3,5-dibromo-4-nitroso-benzenesulfonic acid (DBNBS). The
      signal recorded was unambiguously assigned to the methyl radical adduct. DBNBS
      was added to isolated rat liver mitochondria energized with succinate, and the
      methyl radical adduct was observed. The addition of NADH, NADPH, inhibitors of
      the respiratory chain, and of monoaminoxidase (MAO) inhibitors did not cause any
      relevant modification in the yield of radical adduct formation. Boiling and the
      addition of a non-ionic detergent inhibited the formation of the radical adduct,
      while experiments carried out under hypoxic conditions generated a significant
      increase in methyl radical formation. Further experiments were carried out on sub
      mitochondrial particles (SMP) giving rise to, basically, the same results. From
      the above results, we are proposing that haem prosthetic groups are the likely
      source of TBH bioactivation in mitochondria.

PMID- 8282217
TI  - Membrane lipid fluidity affects the nitroxide radical decay of 5-doxyl stearic
      acids in isolated rat hepatocytes.
AB  - We investigated the effect of membrane fluidity on the nitroxide radical decay
      rate of 5-doxyl stearic acid in spin-labeled rat hepatocytes. The half-time
      (t1/2) for the EPR signal decay of 5-doxyl stearic acids incorporated into the
      membranes of isolated rat hepatocytes was 12 min (mean value). When spin-labeled
      hepatocytes were separated into membrane and cytosol fractions, the t1/2 of the
      membrane fraction was prolonged by more than 2 hrs. However, when the cytosolic
      fraction was added to the membrane fraction, the radical decay reaction recovered
      (t1/2 was 27 min). Incubation of hepatocytes with a stream of 95% O2 at 37
      degrees C for 2 hrs prolonged t1/2 by 106% and was associated with a 18% decrease
      in water-soluble antioxidant content. When the measurement temperature was
      changed from 24 degrees C to 37 degrees C, t1/2 was shortened with a decrease in
      the order parameter (S). The t1/2 and S in hepatocytes treated with
      phosphatidylcholine (PC) were reduced by 14% and 0.008, respectively. Conversely,
      after treatment with phosphatidylethanolamine (PE), PC+cholesterol and
      PE+cholesterol, t1/2 and S increased by 14% and 0.014, 20% and 0.018 and 29% and
      0.040, respectively. These findings suggest that the nitroxide radical decay of 5
      doxyl stearic acids incorporated into hepatocyte membranes is mediated by the
      antioxidants in the cytosol fraction, and that the nitroxide radical decay rate
      is affected not only by water-soluble antioxidant content but also by the
      membrane lipid fluidity of the hepatocytes.

PMID- 8282218
TI  - Metabolism of phenyl and alkyl spin adducts of PBN in rat hepatocytes. Rate
      dependence on size and type of addend group.
AB  - The decay of the EPR signal of phenyl and alkyl spin adducts of PBN has been
      monitored in rat hepatocytes. The rate of decay depends on the length of the
      hydrocarbon chain as follows: n-hexyl > n-dodecyl > n-octadecyl. The rate of
      signal decay is faster in the membrane phase than in the aqueous phase for the
      phenyl spin adduct.

PMID- 8282219
TI  - Membrane fluidity of erythrocytes and its modulation by ouabain in essential
      hypertension--an electron paramagnetic resonance study.
AB  - The purpose of the present study was to examine alterations in membrane fluidity
      of erythrocytes in essential hypertension by means of an electron paramagnetic
      resonance (EPR) and a spin labeling method. In addition, we investigated the
      effects of ouabain on the fluidity of erythrocytes, and elucidated a possible
      role of Na+, K(+)-ATPase in the regulation of membrane fluidity in hypertension.
      Erythrocytes obtained from patients with essential hypertension were examined
      compared with those from age-matched normotensive subjects. The EPR spectra for 5
      nitroxide stearate incorporated into erythrocyte membranes were studied. The
      values of the outer hyperfine splitting and order parameter (S) of the EPR
      spectra were significantly higher in patients with essential hypertension than in
      normotensive subjects. This finding shows that the membrane fluidity of
      erythrocytes might be lower in essential hypertension. Ouabain-loading of
      erythrocytes decreased the membrane fluidity (S value was increased). The ouabain
      induced changes were significantly greater in essential hypertension than in
      normotensive subjects. These results demonstrate that the membrane fluidity of
      erythrocytes might be lower in essential hypertension than in normotensive
      subjects. Furthermore, the membrane fluidity might be highly dependent on the
      Na+, K(+)-ATPase activity in essential hypertension, which would suggest an
      abnormality in Na(+)-related cellular functions in hypertension.

PMID- 8282220
TI  - Force field calculations on five membered ring aminoxyl radicals.
AB  - Two force fields (MM2 and Genmol) have been applied to the modeling of five
      membered ring aminoxyl radicals. For the six molecules which were investigated
      the geometry of the conformation with the lowest strain energy was in very good
      agreement with the X-ray geometry. However owing to the high flexibility of five
      membered rings other conformations were shown to have a strain energy close to
      the energy minimum.

PMID- 8282221
TI  - Detection of free radicals in the blood of animals using extracorporeal
      circulation.
AB  - A method was designed to detect free radicals in circulating blood of animals
      using extracorporeal circulation and electron paramagnetic resonance (EPR). An
      arterial-venous shunt was inserted into male Wistar rats between the distal
      abdominal aorta and the inferior vena cava. The polyethylene tube of the shunt
      was flowed through a quartz EPR cell. The circulation was supported by manual
      pumping and maintained at a rate of 3 ml/min. No signal was detected in the blood
      of untreated rats. After a bolus injection of four spin labels, 2,2,6,6
      tetramethyl-piperidine-1-oxyl, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl, 3
      carbamoyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl, and 3-carbamoyl-2,2,5,5
      tetramethyl-pyrroline-1-oxyl, signals from each were detected. The intensity of
      the signal decreased exponentially and the half time was 23.9, 21.6, 47.1, 42.4
      sec, respectively. After administration of ascorbic acid, ascorbyl radical
      signals were detected. This was enhanced by ethylenediaminetetraacetic acid-Fe or
      diethylenetriaminepentaacetic acid-Fe but not desferrioxamine-Fe. This assay
      system is useful in detecting free radicals either administered or generated in
      vivo.

PMID- 8282222
TI  - Hydroxyl radical generation and membrane fluidity of erythrocytes treated with
      lipopolysaccharide.
AB  - The effect of lipopolysaccharide (LPS) and/or bile acids on rat erythrocyte
      membranes was studied in vitro. Addition of LPS isolated from E. coli (J5 mutant)
      into the erythrocyte resulted in the decrease of membrane fluidity as determined
      by spin labelling using electron paramagnetic resonance (EPR). This was
      accompanied by membrane fragility. It was found that hydroxyl radicals were
      generated from erythrocytes treated with LPS by using DMPO spin trapping.
      However, pretreatment of erythrocytes with taurine-conjugated bile acids was
      found to modify the membrane response induced by LPS. Taurocholic acid (TCA) and
      tauroursodeoxycholic acid (TUDCA) prevented the decrease of membrane fluidity
      induced by LPS, and, as a result, the membrane integrity was maintained although
      no significant changes were observed in the amount of hydroxyl radicals produced
      by LPS addition. However, taurochenodeoxycholic acid (TCDCA) exhibited little
      beneficial effect on the dynamic properties and the function of the erythrocyte
      membranes, although the hydroxyl radical declined markedly in the erythrocytes.
      Therefore, it is suggested that TCA and TUDCA have a protective effect against
      LPS-induced membrane fragility by modulating membrane fluidity.

PMID- 8282223
TI  - Radical trapping by PBN during reperfusion in rabbit gastric mucosa.
AB  - Oxygen free radicals have been considered as a cause of ischemia-reperfusion
      injury in several organs, but this injury in a stomach, containing acid, may
      progress to severe damage. Thus, we examined the effect of ischemia-reperfusion
      and milk-intake on rabbit gastric mucosa. The gastric mucosal blood flow was
      increased after milk-intake, and gastric rupture was detected. Superoxide
      dismutase activity measured by an improved nitroblue tetrazolium reduction method
      and thiobarbituric acid reactive substances in serum is increased during ischemia
      reperfusion and milk-intake. By using alpha-phenyl N-tert-butyl nitrone (PBN) as
      a spin trap and electron paramagnetic resonance (EPR), we detected lipidic
      radicals from tissue samples in chloroform-methanol solvent only during
      reperfusion and milk-intake period; no signal was detected before. The EPR signal
      of spin adducts obtained in the sample after ischemia-reperfusion and milk-intake
      would be a mixture of peroxyl and alkoxyl radicals from the analysis of coupling
      constants.

PMID- 8282224
TI  - Free radical formation induced by ultrasound and its effects on strand breaks in
      DNA of cultured FM3A cells.
AB  - Recent sonochemical studies have revealed that active oxygen species are formed
      by pyrolysis of water molecules due to high temperature cavitation bubbles. When
      aqueous solutions of DNA were sonicated, single-strand breaks and double-strand
      breaks of DNA were observed. Formation of double-strand breaks due to mechanical
      effects of cavitation and formation of single-strand breaks mostly due to free
      radicals were indicated. The sonochemically generated radicals from DNA
      constituents due to H atom and OH radical reactions, and pyrolysis processes,
      were identified by spin trapping with 3,5-dibromo-2,6-dideuterio-4-nitrosobenzene
      sulfonate. When suspensions of mouse mammary carcinoma FM3A cells and aqueous
      solutions of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) were exposed to 1 MHz
      ultrasound in the presence of Ar, a good correlation between DMPO-OH formation
      and the cell killing induced by ultrasound were observed. Although single-strand
      breaks of DNA in the cells were observed at the maximum intensity of DMPO-OH
      formation and cell killing, double-strand breaks were not. Free radical formation
      by ultrasound in aqueous solutions and its relation to DNA strand breaks in vitro
      and in vivo are discussed.

PMID- 8282225
TI  - Nitric oxide interaction with lactoferrin and its production by macrophage cells
      studied by EPR and spin trapping.
AB  - The production of nitrate (NO3-) and nitrite (NO2-) from macrophage-derived NO
      was studied using EPR and spin trapping. The formation of NO3- was determined via
      EPR in reactions involving the iron-binding protein, lactoferrin. The formation
      of NO2- was determined via EPR/spin trapping in the reaction between NO2- and
      H2O2. Dissolved nitric oxide (NO.) was reacted with lactoferrin yielding an EPR
      spectrum (77 degrees K) different from the normal EPR spectrum obtained for
      lactoferrin, suggesting that NO. interacts with the ferric ions bound to
      lactoferrin forming a ferric-nitrosyl type complex. The EPR spectrum (77 degrees
      K) of this ferric-nitrosyl type complex was also observed in the supernatant
      fluid of macrophage cell suspensions following their stimulation with
      lipopolysaccharide (LPS). During LPS stimulation of macrophages, these cells
      generate NO. which in turn produces NO3- and NO2-. The ferric-nitrosyl type
      complex is formed in a reaction mixture containing apolactoferrin and bicarbonate
      following the reaction of Fe+2 with NO3-, generated from macrophage-derived
      NO(.), to produce Fe+3 and NO(.). Furthermore, in an acidic medium, NO2- reacts
      with H2O2 forming peroxynitrous acid (HOONO) which rapidly decomposes into
      hydroxyl radicals (.OH) and the nitrogen dioxide (NO2.) radical. In the
      supernatant fluid of LPS-stimulated macrophage suspensions, the production of .OH
      was verified by spin trapping using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as
      the spin trap and ethanol as the .OH scavenger. The EPR spectra corresponding to
      the DMPO-OH and the DMPO-hydroxyethyl adducts were identified.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8282226
TI  - Use of nitroxides as MRI contrast agents to study in vivo carbon tetrachloride
      induced hepatotoxicity in rats.
AB  - CCl4 and related compounds, such as halothane, are metabolized by the liver to
      form free radical intermediates, which are thought to be implicated in the
      hepatotoxic response. Two to three hours following CCl4 exposure (i.p.) there is
      a localized edematous region surrounding the portal vein which is observable by
      proton MRI in vivo. Enhancement of the CCl4-induced edematous region was possible
      using Gd-DTPA, a paramagnetic contrast agent. However, with the use of a
      nitroxide contrast agent (3-PCA) there was no enhancement, but rather a
      significant diminution of the CCl4-induced edematous response. These results
      suggest that the nitroxide contrast agents, which are themselves free radicals,
      act as free radical scavengers and therefore reduce the formation of the CCl4
      induced hepatic 'damage' observed in proton MR images.

PMID- 8282227
TI  - In vivo EPR measurement of radical reaction in whole mice--influence of inspired
      oxygen and ischemia-reperfusion injury on nitroxide reduction.
AB  - In vivo EPR measurements were carried out with whole mice to evaluate the
      influence of inspired oxygen and ischemia-reperfusion injury on spin-clearance of
      the nitroxide radicals which were administered intravenously or intramuscularly.
      Nitroxide radicals in head, abdomen, or muscle domains were composed of sharp
      triplet lines. The peak heights decreased gradually with time. The reduction of
      nitroxide radicals depended both on the inspired oxygen concentration and on the
      domains. Femoral ischemia-reperfusion injury also affected spin-clearance of the
      nitroxide radical in the thigh. The results were discussed with regard to the
      generation of active oxygen species.

PMID- 8282228
TI  - The syringe nitroxide free radical--Part II.
AB  - Some plastic syringes introduce a nitroxide free radical into the fluids they
      contain. The EPR spectrum shows a triplet with aN = 17.0 +/- 0.1 G in plasma. We
      report here that this nitroxide/hydroxylamine couple serves as an antioxidant
      system, whose redox potential appears to be between that of vitamin C and vitamin
      E. This adventitious antioxidant can alter the course of free radical processes.

PMID- 8282229
TI  - Beta-phosphorylated five membered ring nitroxides. Synthesis and EPR study.
AB  - A series of stable beta-phosphorylated five membered ring nitroxides was prepared
      by intramolecular aminomercuration of alkenyl alpha-aminophosphonates. The
      structure of these nitroxides was deduced from their 13C and 31P coupling
      constants and from force field calculations.

PMID- 8282230
TI  - Photosensitized generation of superoxide radical in aprotic solvents: an EPR and
      spin trapping study.
AB  - The UV or visible irradiation of pigments such as curcumin, anthralin,
      benzanthrone, 1,8-dihydroxyanthraquinone, and rose bengal- or eosine-complexes
      with cationic surfactants in aerated aprotic solvents, such as benzene, toluene,
      acetone, n-heptane, cyclohexane, in the presence of 5,5-dimethyl-1-pyrroline-N
      oxide (DMPO) generates EPR spectra with hyperfine splitting constants (hfsc's) aN
      = 12.75 G, a beta H = 10.50 G, a gamma H = 1.26 G in toluene, 12.83 G, 10.64 G,
      1.24 G in benzene, 12.75 G, 10.19 G, 1.35 G in acetone and 12.54 G, 10.46 G, 1.38
      G in n-heptane and cyclohexane. These spectra are similar to those observed when
      DMPO reacts with 18-crown-6 ether-solubilized KO2 in the respective solvents and
      suggests that the photoinduced EPR spectra can be safely assigned to the
      DMPO/superoxide radical adduct (1). A correlation between the hfsc's of 1 and
      solvent parameters, the solvent acceptor number AN and the Kosower Z value, has
      been evaluated in terms of its usefulness for the identification of the
      DMPO/superoxide adduct in organic media.

PMID- 8282231
TI  - Sonochemistry of acetone and acetonitrile in aqueous solutions. A spin trapping
      study.
AB  - The 50 kHz sonolysis of argon-saturated water-acetone and water-acetonitrile
      mixtures was studied by EPR and spin trapping with 3,5-dibromo-4
      nitrosobenzenesulfonate over a wide range of solvent composition. For both
      systems a single maximum was observed for the spin adduct yield of methyl
      radicals and of the radicals formed by H-abstraction from acetone and
      acetonitrile. These results combined with previous studies of water-methanol and
      water-ethanol mixtures indicate that the greater the vapor pressure of the
      volatile organic component, the lower the concentration of organic solute at
      which the maximum radical yield occurs. Methyl radicals from acetone are formed
      by C-C bond scission in the collapsing argon bubbles. For acetonitrile, C-H bond
      scission at high temperature is followed by H-addition to the triple bond and the
      decomposition of this intermediate radical to form methyl radicals. Since Anbar
      has shown (Science 161, 1343, 1961) that sonoluminescence and acoustic cavitation
      occur during the impact of liquid water on water with linear velocities similar
      to those of collapsing ocean waves, the sonochemistry of nitriles is of interest
      to chemical evolution studies.

PMID- 8282232
TI  - On the substituent effect of tert-butylaminoxyl group for the acid-dissociation
      equilibria of alpha-substituted acetic acids.
AB  - alpha-Substituted acetic acids with tert-butylaminoxyl groups, t-BuN(O.)-CHX
      COOH, were produced as spin adducts in gamma-irradiated aqueous solutions of
      amino acids and peptides with a spin trap, 2-methyl-2-nitrosopropane. The spin
      adducts were isolated and characterized by means of high-performance liquid
      chromatography and EPR spectroscopy. Their EPR spectra in acidic region changed
      reversibly with pH through the acid-dissociation of the carboxyl groups. The
      spectra at pH around the pK value were weighted averages of acid forms and
      conjugate base forms. The pKCOOH values for the dissociation were determined to
      be 3.0, 3.2, 2.0, 1.8, and 1.6 for t-BuN(O.)-CH2COOH, t-BuN(O.)-CH(CH3)COOH,
      NH3+CH2CONHCH(COOH)N(O.)-t-Bu, and NH3(+)-*CH(CH3)-CONH-*CH(COOH)N(O.)-t-Bu [a
      pair of diastereomers], respectively. The electron-withdrawing character of the
      aminoxyl group is responsible for the observation that the pKCOOH values are
      lower than those of X-CH2-COOH. The substituent effect of the tert-butylaminoxyl
      group on the acid-dissociation equilibria of alpha-substituted acetic acids was
      investigated in relation to the Taft equation. The aliphatic polar substituent
      constant (sigma*) has been evaluated to be approximately +0.9 for the t
      BuN(O.)CH2 group [or the inductive substituent constant sigma 1 approximately
      +0.4 for the t-BuN(O.) group].

PMID- 8282233
TI  - Spin trapping study of superoxide production in ferrous ion oxidation.
AB  - The oxidation of Fe2+ was investigated by electron paramagnetic resonance (EPR)
      spin trapping techniques with N-t-butyl-alpha-phenylnitrone (PBN) and dimethyl
      sulfoxide. Under pure oxygen, the spin adduct PBN/.OCH3 was rapidly generated by
      the addition of Fe2+ (0.2-1.2 mM) into phosphate buffer containing
      ethylenediaminetetraacetate (EDTA), dimethyl sulfoxide and PBN at pH 7.4, but it
      decayed. The decay process of PBN/.OCH3 consists of two components. The fast
      decay was dependent on Fe2+ concentration. Another was due to destruction of the
      spin adduct by superoxide anion (.O2-), because superoxide dismutase (SOD)
      markedly prevented the decay. Catalase decreased the yield of PBN/.OCH3. When
      Fe(3+)-EDTA and ascorbate were used instead of Fe(2+)-EDTA, similar phenomena
      were detected. These results demonstrate that Fe2+ reacts with O2 to generate .O2
      , then H2O2, which produces .CH3 by the reaction with Fe2+ and dimethyl
      sulfoxide. The .OCH3 radical results from the reaction between .CH3 and O2. The
      adduct PBN/.OCH3 decays by the reaction with Fe2+ and .O2-.

PMID- 8282234
TI  - Effective inhibition of hydroxyl radicals by hydroxylated biphenyl compounds.
AB  - In aqueous media, approximate rate constants for the reactions between hydroxyl
      radicals (.OH) and biphenyl compounds such as dehydrodieugenol, magnolol,
      honokiol, dehydrodidihydroeugenol, dehydrodivanillyl alcohol, and
      dehydrodicreosol were estimated by competition reactions for .OH between these
      biphenyls and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). By measuring the decrease
      in the height of the EPR signals of the .OH spin adduct, rate constants in the
      order of 10(9) to 10(10) M were measured.

PMID- 8282235
TI  - The spin trapping of superoxide and hydroxyl free radicals with DMPO (5,5
      dimethylpyrroline-N-oxide): more about iron.
AB  - The reaction of superoxide with the spin trap DMPO (5,5-dimethylpyrroline-N
      oxide) is widely used to study superoxide production as well as issues associated
      with the superoxide-related formation of hydroxyl radical. However, the
      interpretation of observed intensities of DMPO/.OOH and DMPO/.OH signals in
      electron paramagnetic resonance spin trapping experiments is not without its
      difficulties. In this paper, I report experiments that demonstrate: 1. That the
      flux of superoxide formation in a DMPO spin trapping experiment can alter the
      apparent importance of weak DMPO/.OH signals; 2. That iron can influence the
      DMPO/.OOH spin trapping results; 3. That there is very little spontaneous
      breakdown of DMPO/.OOH to form DMPO/.OH.

PMID- 8282236
TI  - Luteoskyrin, an anthraquinoid hepatotoxin, and ascorbic acid generate hydroxyl
      radical in vitro in the presence of a trace amount of ferrous iron.
AB  - Luteoskyrin is a bis-dihydroanthraquinone mycotoxin produced by Penicillium
      islandicum Sopp. By using EPR spin-trap techniques we investigated whether .OH is
      formed in a model system containing ascorbic acid and the toxin. In the presence
      of DMSO and DMPO, we found signals of DMPO-CH3, a more specific and reliable
      signature of .OH than DMPO-OH, together with the signals of ascorbyl radical.
      DMPO-CH3 signals increased with time of incubation up to 5.5 min. The DMPO-CH3
      formation depended completely on both luteoskyrin and ascorbic acid, and
      deferoxamine, an iron-chelator, inhibited its formation. The signals disappeared
      in the presence of excess amount of catalase whereas SOD showed no effect. These
      results suggest that .OH is formed from ferrous ion present in the mixture of
      H2O2 generated from ascorbic acid and luteoskyrin.

PMID- 8282237
TI  - [Methylation of DNA in tissue of ovarian malignant tumors in women].
AB  - DNA methylation level from woman ovarian malignant tissues was investigated by
      32P postlabeling of the single nucleotides, separation on TLC with followed
      autoradiography and Cerenkov counting. Slight differences in DNA methylation
      extent were found in malignant ovarian tumors as compared to normal myometrium
      and benign uterine tumor [myomas]. Lowest level of m5dC in relation to C and also
      in relation to total DNA was found in carcinoma embryonal tissue whereas maximal
      DNA methylation level was obtained in folliculoma tissue. This preliminary report
      needs further investigation of particularly genes methylation.

PMID- 8282238
TI  - [Effect of intraventricular hemorrhage in newborns on levels of certain
      prostanoids in blood plasma].
AB  - Recent studies suggest that eicosanoids might be involved in pathogenesis of
      vascular problems in preterm infants. The aim of the study was determine the
      concentrations most potent occurring vasoactive substances: Thromboxane A2 (TxA2)
      promoting vasoconstriction and prostacyclin (PGI2) causing vasodilation of
      vascular smooth muscles. We assessed the concentrations of stable metabolites
      TxA2-TxB2 and PGI2-6 keto PGF1 alpha in blood plasma by RIA method. It was found
      that neonates with RDS + IVH had significantly elevated TxB2 and 6 keto PGF1
      alpha compared to healthy newborns, with transient tachypnoea and with RDS. High
      concentrations of thromboxane and prostacyclin metabolites in newborns plasma
      with IVH suggest a causative role of eicosanoids in pathogenesis of haemorrhage.
      The cells of impaired blood vessels may be probable source of these eicosanoids.

PMID- 8282239
TI  - [Laparoscopy in clinical practice. I. Indications].
AB  - In the paper the authors analyzed indications to 1527 laparoscopies. The most
      frequent indications were: sterility (72.2%) and suspicions of adnexal tumours or
      extrauterine gravidity (14.1%). In 173 diagnostically difficult cases laparotomy
      was avoided. In these cases laparoscopy allowed to exclude the pelvic pathology
      or to quality to laparoscopic operation of ovarian cysts and intact tubal
      pregnancy. Diagnostic and operative laparoscopy give the possibility of quick
      diagnosis in diagnostically difficult cases and enables avoidance of laparotomy
      in many cases.

PMID- 8282240
TI  - [Laparoscopy in clinical practice. II. Usefulness in diagnosis of sterility].
AB  - The paper presents results of 1099 laparoscopies performed in sterility.
      Laparoscopy was made in the second phase of the menstrual cycle, 5 to 7 days
      after probable ovulation, as a last stage in diagnosis of sterility. Normal state
      of genital organs and minor pelvis was noted in 20.9% of investigated patients.
      In the remaining more than one etiologic factor was found, which may influence
      the sterility. The authors concluded, laparoscopy is valuable, accessory method
      in the diagnosis of sterility, which enables sometimes to find the etiologic
      factor in patients with "unexplained infertility".

PMID- 8282241
TI  - [Laparoscopy in clinical practice. III. Complications].
AB  - In the paper authors made analysis of complications, which have appeared among
      1527 laparoscopies. The authors noted complications in 14 cases (0.91%) among the
      whole laparoscopic interventions. The most frequent complication was subcutaneous
      oedema, which was noted in 7 cases (0.46%). Injury of internal organs was noted
      in 6 cases (0.39%) and cardiac arrest in 1 case (0.06%). In author's opinion
      laparoscopy carry a small risk of complications.

PMID- 8282242
TI  - [Phagocytosis and bactericidal capacity of polymorphonuclear neutrophils in
      neonates].
AB  - Phagocytosis and bactericidal capacity of polymorphonuclear neutrophils (PMN)
      obtained from umbilical venous blood was estimated in 30 neonates and their
      mothers by the use of fluorochrome microassay of Pantazis and Kniker.
      Phagocytosis of Staphylococcus was similar in both groups and controls, while
      intracellular bacteria killing was significantly impaired in PMN obtained from
      the neonates. These results may indicate that increased susceptibility to
      infection observed in neonates may be partly caused by PMN function impairment.

PMID- 8282243
TI  - [Effect of immunomodulators on selected functions of neonatal polymorphonuclear
      neutrophils in vitro].
AB  - Phagocytosis, bactericidal capacity, production of superoxide anions O2- and
      expression of receptor for the Fc portion of IgG of polymorphonuclear neutrophils
      (PMN) were estimated in umbilical venous blood of neonates and their mothers. We
      also evaluated the influence of immunomodulating agents on these parameters. The
      influence of the maternal serum on the function of neonatal PMN was examined. The
      obtained results indicate that functional defect of neonatal PMN may be corrected
      under the influence of the maternal serum and/or immunomodulating agents.

PMID- 8282244
TI  - [Prenatal diagnosis of chromosomal aberrations in first trimester pregnancy-
      methods for cytogenetic analysis of the trophoblast].
AB  - Prenatal diagnosis of chromosomal abnormalities by chorionic villus (CVS) in the
      first trimester of pregnancy is presented. Trophoblast biopsy techniques, methods
      of cytogenetic analysis of this tissue as well as technical and diagnostic
      problems in fetal karyotyping are described.

PMID- 8282245
TI  - [A seldom used method of conservative treatment for hemorrhage in a pregnant
      patient with placenta praevia centralis].
AB  - The subject described is the method of conservative treatment in the case of the
      placenta praevia cervicalis. Bilateral ligation of the ramus descensus arteriae
      uterinae together with the tamponing of the uterus cervix can be effective in
      staunching hemorrhages caused by the inability to separate the placenta implanted
      in the muscular tissue of the cervix. Due to the remaining fragments of the
      placenta, it is necessary to test the solution of HCG in the serum. The described
      method of treatment allows the sex organ to be left intact.

PMID- 8282246
TI  - [Lamellar ichthyosis, uncommon genodermatosis].
AB  - Authors have performed the main types of the ichthyosis, the emphasis has been
      placed on Lamellar Ichthyosis, because the case of this rare disease occurred in
      a hospital in Pleszew. The paper contains the case report and detailed
      description of Lamellar Ichthyosis: clinical signs, prenatal diagnosis and
      treatment.

PMID- 8282247
TI  - Gene expression in Barrett's mucosa: acute and chronic adaptive responses in the
      oesophagus.

PMID- 8282248
TI  - Capturing clinical activity--coming to terms with information.

PMID- 8282249
TI  - Nocturnal oesophageal motor activity is dependent on sleep stage.
AB  - Simultaneous overnight oesophageal pH and manometric and sleep
      electroencephalographic recordings were performed in eight healthy subjects, aged
      20-38 years, to test the hypothesis that the frequency of primary, swallow
      related contractions decreases progressively with deeper sleep stages whereas the
      frequency of secondary contractions remains constant throughout the night. During
      the nocturnal period (2300 to 0700), periods of oesophageal motor quiescence were
      interspersed by clusters of contractions detected 5 and 15 cm above the lower
      oesophageal sphincter. Primary contractions decreased in frequency from 1.42/min
      (median) during arousal periods to 0.22/min during stage 1 sleep, 0.05/min during
      stages 2 to 4 combined, and 0.03/min during rapid eye movement (REM) sleep.
      Secondary contractions were also most frequent during arousal periods (0.51/min)
      and they, too, decreased in frequency during stage 1 (0.35/min) and stages 2 to 4
      combined (0.08/min). During REM sleep, however, the frequency of secondary
      contractions increased (0.50/min) to levels noted during arousal and stage 1
      sleep. Compared with primary contractions, secondary contractions had a lower
      amplitude (51.9 hPa v 76.0 hPa; p = 0.0078) and a shorter duration (3.08 v 4.06
      s; p = 0.0078). The results of this study suggest that there is no intrinsic
      oesophageal motor activity in the absence of a stimulatory input from the central
      nervous system and that the increased number of secondary contractions during REM
      sleep may be a result of an REM related increase in autonomic nervous system
      activity although a temporary decrease of efferent inhibitory influences cannot
      be ruled out. Nocturnal contraction clusters comprise both primary contractions
      during arousals and stage 1 sleep and secondary contractions during REM sleep.

PMID- 8282250
TI  - Peptic ulcer, cimetidine, and motor neurone disease--a record linkage study.
AB  - A previous cohort study suggested that there might be an association between use
      of cimetidine and motor neurone disease. The Oxford Record Linkage Study was used
      to explore this hypothesis. In the analysis the presence of a peptic ulcer in
      patients after 1976 was taken as a proxy for cimetidine (and ranitidine) use. The
      past history of 540 patients with motor neurone disease in this period was
      compared with that of 1370 patients with multiple sclerosis (neurological
      controls) and over 240,000 control patients with a variety of other conditions.
      Among those with motor neurone disease, five had been previously admitted to
      hospital with peptic ulcer in comparison with an expected number of 7.4
      (morbidity ratio 0.68, 95% confidence interval: 0.2 to 1.6). The corresponding
      figures for those with multiple sclerosis were 12 and 9.7 respectively (morbidity
      ratio 1.24, 95% confidence interval: 0.6 to 2.2). This study provides some
      evidence against the possibility that cimetidine (and ranitidine) are related to
      motor neurone disease.

PMID- 8282251
TI  - Two year maintenance treatment of duodenal ulcer disease with ranitidine 150 mg:
      a prospective multicentre randomised study. GEMUD (Groupe d'Etude de la Maladie
      Ulcereuse Duodenale).
AB  - Maintenance treatment of duodenal ulcer (DU) with ranitidine 150 mg/day was
      compared with placebo in a two year prospective multicentre randomised study.
      Three hundred and ninety nine patients were included (mean age: 44.7 years, M/F
      ratio = 2.47/1; 37.6% of smokers) in placebo (n = 202) and ranitidine (n = 197)
      groups. Efficacy was assessed by the length of time to the first ulcer pain
      attack (with or without endoscopic confirmation) or DU complication. One hundred
      and fourteen patients of 399 (28.6%) had incomplete follow up. Actuarial survival
      curves of patients without ulcer pain (26 and 53% at two years in placebo and
      ranitidine groups, respectively) were significantly different (p < 0.0001).
      Endoscopies were performed depending on physicians' decision (mainly where there
      was severe pain or complication). Patients without relapses from endoscopy were
      more frequent in the ranitidine group (83%) than in the placebo group (47%, p <
      0.0001). A greater incidence of complications, mainly bleeding, was also seen in
      the placebo group (13 complications v two in the ranitidine group, p < 0.002). No
      factor predicting DU relapse was identified. No important side effect was
      encountered. Ranitidine 150 mg/day is effective and well tolerated in preventing
      ulcer pain attacks and DU complications for up to two years.

PMID- 8282252
TI  - Perforated peptic ulcer over 56 years. Time trends in patients and disease
      characteristics.
AB  - Perforated gastroduodenal ulcer was studied in 1483 patients in the Bergen area
      during the years 1935-90 to discover time trends in age and sex, disease
      characteristics, treatment, and outcome. The male:female ratio fell from 10:1 to
      1.5:1, median age increased from 41 to 62 years. Most perforations were found in
      the duodenum in 1935-64, and in the pyloric and praepyloric area in 1965-90.
      There was a 10% occurrence of gastric ulcers throughout the study period. Ulcer
      site was related to age (more gastric and less duodenal perforations with
      increasing age) and sex (more pyloric and less duodenal ulcers among women).
      There were twice as many perforations in the evening compared with the early
      morning. The diurnal variation was more pronounced for duodenal and pyloric than
      for gastric and praepyloric perforations. Circadian and seasonal variation of
      ulcer perforation did not change during the 56 years studied. Treatment delay
      increased from median five hours to median nine hours. Infective complications
      and mortality fell with the introduction of antibiotics around 1950. General
      complications has increased in recent years because of the increase of elderly
      patients. Among patients who died, the proportion with associated disease rose
      from 27 to 85% during the study period.

PMID- 8282253
TI  - Epidemiology of, and risk factors for, Helicobacter pylori infection among 3194
      asymptomatic subjects in 17 populations. The EUROGAST Study Group.
AB  - The cross sectional study describes the prevalence of infection with Helicobacter
      pylori as determined by a serodiagnostic assay in over 3000 asymptomatic
      subjects, in two age groups 25-34 years and 55-64 years, from 17 geographically
      defined populations in Europe, North Africa, North America, and Japan, using a
      common protocol for blood collection and serological testing. In all populations
      combined, the prevalence of infection was higher in the older age group (62.4%)
      than in the younger age group (34.9%). There was no difference in prevalence of
      infection between men and women. Subjects with higher education had considerably
      lower levels of infection (34.1%) compared with subjects with education up to
      secondary level (46.9%) or those with primary education only (61.6%). This trend
      was confined to the older of the two age groups. In contrast a trend of
      increasing prevalence of infection with increasing body mass index was confined
      to the younger of the two age groups. There was no effect of smoking or alcohol
      consumption on the prevalence of infection after adjusting for the other risk
      factors. There was considerable variation in the prevalence of infection between
      the 17 populations but, within populations, low education standard was
      consistently and positively associated with the prevalence of infection.

PMID- 8282254
TI  - Prevalence of Helicobacter pylori infection and its effect on symptoms and non
      steroidal anti-inflammatory drug induced gastrointestinal damage in patients with
      rheumatoid arthritis.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter (H pylori) are
      both associated with an increased risk of peptic ulceration and gastropathy. It
      is not known, however, if there is an interaction between these two agents, and
      thus whether or not screening for H pylori before NSAID treatment is of value.
      The aim of this study was to find out if H pylori potentiates the damaging
      effects of NSAIDs. Fifty two patients with rheumatoid arthritis requiring
      longterm NSAID treatment were studied. Dyspeptic symptoms were assessed according
      to a standardised questionnaire. Gastroscopy was performed after a one week
      washout period during which NSAIDs were discontinued. Gastric and duodenal
      mucosal damage was graded endoscopically. H pylori was identified by biopsy
      urease test and by histological tests. Investigations were repeated after one
      month's treatment with an NSAID. Patients with H pylori infection (n = 26) had a
      higher dyspeptic symptom score (p < 0.05). One patient with duodenal ulcer (H
      pylori +ve) and two with endoscopic gastritis (both H pylori +ve) were excluded
      from further study. Forty two subjects completed the study. After treatment there
      was a rise in the gastric damage score both in the H pylori +ve (p = 0.06) and
      the H pylori -ve (p < 0.005) groups. There was no difference in the extent of
      increase in grade or the final grade at the end of the treatment period between
      the H pylori +ve and -ve patients. It is concluded that H pylori infection is
      associated with increased dyspeptic symptoms in patients receiving NSAIDs but
      that it does not potentiate NSAID gastropathy.

PMID- 8282255
TI  - When is Helicobacter pylori infection acquired?
AB  - Cross sectional surveys have shown an increasing prevalence of Helicobacter
      pylori (H pylori) infection with increasing age in Western populations. The aim
      of this study was to examine the pattern of acquisition of H pylori infection
      over a 21 year period in a group of 141 adults who had blood samples and serum
      stored in 1969, 1978, and 1990. A prevalence of H pylori antibody of 39% in 1969
      serum samples, 40.9% in 1978, and 34.8% in 1990 was found when assessed by an
      enzyme linked immunosorbent assay (ELISA). Of the 86 subjects who were
      seronegative in 1969, only six (7%) were seropositive in 1990. These data suggest
      that a cohort effect may contribute to the pattern of increasing prevalence of H
      pylori infection seen with increasing age. Acquisition of infection in adults is
      rare. It is unlikely, therefore, that reinfection will occur after successful
      eradication.

PMID- 8282256
TI  - DNA damage in the stomach after vagotomy measured by 32P-postlabelling.
AB  - This study analysed gastric mucosal DNA by 32P-postlabelling in a series of
      patients who have had previous vagotomy for benign peptic ulcer disease. DNA
      adduct levels were found to be significantly higher in patients who had had
      previous truncal vagotomy than in those who had had previous highly selective
      vagotomy (p < 0.001). Intragastric bile concentrations were also considerably
      higher in patients after truncal vagotomy but there was no correlation between
      intragastric bile concentrations and DNA adduct levels. These results suggest
      that, although duodenogastric reflux may be a cause of gastric mucosal DNA damage
      in the stomach after vagotomy, measurement of total intragastric bile does not
      accurately reflect genotoxic insult.

PMID- 8282257
TI  - Chronic nicotine intake causes vascular dysregulation in the rat gastric mucosa.
AB  - Chronic cigarette smoking has adverse effects on peptic ulcer disease because the
      healing of ulcers is delayed and the incidence of relapses is enhanced. Short
      term intake of nicotine induces vascular damage in the rat gastric mucosa, but
      the pathophysiological mechanisms of nicotine's action in the stomach are largely
      unknown. In this study rats were treated with nicotine, added to their drinking
      water, for 50 days. They were then anaesthetised and their stomachs perfused with
      acidified acetylsalicylic acid (ASA). Chronic nicotine treatment failed to change
      the effects of acidified ASA to induce gastric mucosal acid back diffusion,
      haemorrhagic damage and bleeding. Basal blood flow in the gastric mucosa was also
      unchanged by chronic nicotine intake, whereas the mucosal hyperaemia evoked by
      ASA induced acid back diffusion was averted. The concentrations of
      sulfidoleukotrienes were significantly augmented in the gastric wall of nicotine
      treated rats. These data show that chronic nicotine intake causes dysregulation
      of the gastric microcirculation, an effect that is associated with biochemical
      changes in the stomach. This study thus substantiates the adverse effects of
      smoking on gastric mucosal pathophysiology. These data suggest that inappropriate
      regulation of gastric mucosal blood flow inhibits recovery from gastric mucosal
      injury in smokers.

PMID- 8282258
TI  - Determination of the histological distribution of insulin like growth factor 1
      receptors in the rat gut.
AB  - The histological distribution of insulin like growth factor 1 (IGF 1) receptors
      in the rat gut was studied. Immunostaining of IGF 1 receptors identified
      localisation on the villus epithelium, in the crypts, and in Brunner's glands of
      the small intestine. These tissues represent areas of high cell
      growth/differentiation, division, and macromolecular synthesis respectively,
      which constitute biological activities long associated with IGF 1. Cellular
      localisation of IGF 1 receptors was seen in the lamina propria by IGF 1 receptor
      immunostaining and ligand binding of biotinylated IGF 1. IGF 1 receptor
      immunostaining in the spleen showed receptor localisation to the splenic pulp
      thus pointing to macrophages as the possible IGF 1 receptor positive cells in the
      lamina propria. The results further implicate IGF 1 as an important growth factor
      in gut maintenance.

PMID- 8282259
TI  - Human papillomavirus 16 DNA in NIH3T3 cells transformed by colonic cancer
      cellular DNA.
AB  - Human papillomavirus (HPV) 16 DNA is closely associated with human cancers. It
      has been identified as an aetiological agent in cervical cancers and, recently,
      in colonic neoplasms. To further understand the role of HPV 16 DNA in colorectal
      carcinogenesis, NIH3T3 cells were transformed with high molecular weight DNA from
      colonic cancer cells and the expression of HPV 16 DNA detected. Both human Alu
      and HPV 16 DNA sequences were found in the type II foci of CC-M2T cells by
      Southern blot hybridisation. Additionally, 100% tumorigenicity in nude mice was
      seen. This study shows the transfection of HPV DNA from colonic cancers into
      NIH3T3 mouse cells and suggests that HPV type 16 might be associated with the
      malignant transformation of colonic cells.

PMID- 8282260
TI  - Endoscopic extraction of bile duct stones: management related to stone size.
AB  - Endoscopic sphincterotomy has become the first line treatment for patients with
      common bile duct (CBD) stones. This technique may fail, however, due to difficult
      anatomy, previous surgery, periampullary diverticula or the presence of a large
      stone. The importance of stone size to the success of endoscopic sphincterotomy
      has not been fully assessed. A prospective study was carried out over the period
      January 1987 to December 1989 on 100 patients (45 male, 55 female, median age 69
      years, range 19-97) with CBD stones in which a policy of early duct clearance was
      followed. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and
      the stone size and number recorded from the cholangiograms and corrected for
      magnification. Sphincterotomy was performed using a diathermy unit with a cutting
      current and stones were extracted using a balloon catheter or a Dormia basket. Of
      the 100 patients with CBD stones receiving ERCP, successful clearance of the
      biliary tree was possible in seven without endoscopic sphincterotomy and five
      were felt to be unsuitable for endoscopic sphincterotomy. Of the remaining 88
      patients endoscopic sphincterotomy was successful in 75 (85%). Of the 75 patients
      having endoscopic sphincterotomy stone clearance was successful in 44 (59%).
      There were no deaths and only four complications, which rapidly resolved on
      conservative treatment (two acute pancreatitis, two bleeding). The number of CBD
      stones present was similar in those patients with successful endoscopic
      sphincterotomy and duct clearance (median 1, range 1-10, n = 44) as in those in
      whom it failed (median 2, range 1-6, n = 31). In contrast there was a highly
      significant difference when stone size was analysed (successful clearance median
      stone size 10 mm, range 3-27 mm; unsuccessful: median 18 mm, range 10-42,
      p<0.001). Stones less than 10 mm in diameter (n=21) were all removed successfully
      whereas in patients with stones over 15 mm (n=25) only three were removed
      endoscopically (12%). All patients with evidence of residual stones had
      additional treatment. Of these 31 patients, 10 had surgery, 11 had insertion of
      an endoprosthesis, and 10 had dissolution treatment with methyl-tert-butyl ether
      through a nasobiliary catheter. This study shows the importance of stone size to
      the success rate of endoscopic removal of bile duct stones.

PMID- 8282261
TI  - Comparison of two sialosyl-Tn binding monoclonal antibodies (MLS102 and B72.3) in
      detecting pancreatic cancer.
AB  - An immunohistochemical study has been carried out to compare and contrast the
      cellular distribution of two different sialosyl-Tn antigen binding monoclonal
      antibodies, MLS102 and B72.3, in the pancreas. MLS102 but not B72.3 monoclonal
      antibody binding increases with the content of the sialosyl-Tn epitopes. It was
      found that all 13 pancreatic cancer specimens bound both MLS102 and B72.3
      monoclonal antibodies. Their cellular distribution in the cancer was virtually
      identical. Fifteen of 20 (75%) patients with chronic pancreatitis and five of 10
      (50%) normal subjects were B72.3 positive, but MLS102 was completely negative in
      the latter group. Both monoclonal antibodies bound fetal pancreas diffusely.
      Thus, when pancreatic ductal cells have undergone malignant transformation, like
      the fetal pancreas, they express cell surface and secreted glycoconjugates with
      increased sialosyl-Tn epitopes suggesting enhanced 2-6 sialosyltransferase
      activity. This study shows that MLS102 is an extremely sensitive and specific
      tumour marker in the pancreas and that it is better than B72.3 in distinguishing
      pancreatic cancer from normal and chronic pancreatitis.

PMID- 8282262
TI  - Toxic megacolon: the knee-elbow position relieves bowel distension.
AB  - Toxic megacolon complicating inflammatory or infective colitis carries a high
      morbidity and mortality and surgical intervention is necessary in up to 80% of
      cases. Perforation complicates toxic megacolon in about 35% of cases. After
      perforation, the death rate nears 50%. Gaseous distension of the bowel causes
      considerable discomfort to the patient and increases transmural pressure. The
      latter is thought to cause a reduction in blood flow and may predispose to
      perforation. The use of instruments for colonic aspiration is discouraged,
      because of the high risk of perforation. The successful use of the knee-elbow
      position to relieve bowel distension in two patients with toxic megacolon is
      described.

PMID- 8282263
TI  - Nature and standards of gastrointestinal and liver services in the United
      Kingdom.
AB  - 1. Purpose of the working party: 1.1 To describe the scope of major digestive and
      liver disorders and identify changes in patterns of disease. 1.2 To identify
      diagnostic and therapeutic services required to manage these disorders in the
      United Kingdom. 1.3 To describe the facilities and staffing required to provide
      these services. 1.4 To examine the training requirements for medical, nursing,
      and other support staff. 1.5 To define the part that audit and research should
      play in the provision and maintenance of high quality gastrointestinal and liver
      services.

PMID- 8282264
TI  - Clinical and pathological spectrum of coeliac disease.

PMID- 8282265
TI  - Perioperative endoscopy of the whole small bowel in Crohn's disease.

PMID- 8282266
TI  - Gastric mucosal phospholipids and gastroduodenal diseases.

PMID- 8282267
TI  - [The role of Ca2+/calmodulin-dependent protein kinase II in the cellular signal
      transduction].
AB  - Both Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) and protein
      kinase C (PKC) have been implicated as possible candidates for contributing to
      the induction of long-term potentiation (LTP) in the hippocampus. The induction
      of LTP in the CA1 region of the hippocampus, an event which requires postsynaptic
      Ca2+ influx through NMDA-type glutamate receptors, is blocked by calmodulin
      antagonists and inhibitors of CaM kinase II and PKC. In the present study, we
      describe the activation characteristics of CaM kinase II and PKC through the
      stimulation of glutamate receptors and regulation of the phosphorylation of
      substrates for CaM kinase II in the hippocampus. In cultured rat hippocampal
      neurons, glutamate elevated the Ca(2+)-independent activity of CaM kinase II
      through autophosphorylation, and this response was blocked by specific
      antagonists of the NMDA receptor. In addition, glutamate stimulated the
      translocation of PKC from the cytosol to the membrane fraction through the
      metabotropic glutamate receptor. In the experiments with 32P-labeled cells, the
      phosphorylation of microtubule-associated protein 2 (MAP2) and synapsin I was
      stimulated by the exposure to glutamate. Finally, we demonstrated that high, but
      not low, frequency stimulation applied to two groups of CA1 afferents in the
      slices resulted in the induction of LTP with concomitant long-lasting increases
      in the Ca(2+)-independent and total CaM kinase II activities as well as the
      autophosphorylation. It could be blocked by preincubation of the slices with NMDA
      receptor antagonist. These results suggest that glutamate can activate CaM kinase
      II through NMDA receptors in the induction of LTP and in turn stimulates the
      phosphorylation of target proteins such as MAP2 and synapsin I.

PMID- 8282268
TI  - [A new perfusion technique for vascular vessels].
AB  - A new perfusion technique for isolated vascular preparations is described. The
      cannula inserting method developed by Hongo and Chiba (J. Pharmacol. Methods 9,
      83, 1983) and modified by Tsuji and Chiba (Japan. J. Pharmacol. 34, 95, 1984) is
      useful for observing vascular reactivity in perfused, isolated vessels. In this
      method, 1) applied substances act only from the intraluminal side; 2) vascular
      responses to substances, not only constriction but also dilatation in non-treated
      preparations, are readily obtainable by a single injection of active substances;
      and 3) the vascular reactivity is reproducible over 7-8 hr at 37 degrees C. Our
      modified cannula inserting methods are also described.

PMID- 8282269
TI  - [Effect of MHS-G, an amino acids granule, on hepatic encephalopathy in portacaval
      anastomosis rats].
AB  - Using portacaval anastomosis (PCA) rats as a model with or without injection of
      ammonium acetate, we investigated the effects of MHS-G on the abnormalities of
      electroencephalogram (EEG) and brain amines metabolism in comparison with those
      of SF-1008C, a commercial nutritional preparation for hepatic failure. MHS-G
      (0.68 g/kg, p.o.) clearly improved both the abnormalities of EEG (such as
      reduction of amplitude, increasing delta wave distribution and decreasing beta
      wave distribution) and brain amines metabolism (such as increasing of Trp and
      DOPAC content) after injection of ammonium acetate. Moreover, MHS-G significantly
      increased branched chain amino acid concentrations and decreased aromatic amino
      acid concentrations in plasma and brain in comparison with water, and it
      significantly decreased the ammonia level in plasma in comparison with water and
      SF-1008C. These results suggest that MHS-G has a positive effect on abnormalities
      of EEG and amino acids metabolism in the plasma and brain of PCA rats.

PMID- 8282270
TI  - [Inhibitory action of E3810 on H+,K(+)-ATPase and gastric acid secretion in
      vitro].
AB  - The inhibitory action of (+-)-sodium 2-[(4-(3-methoxypropoxy)-3-methylpyridine-2
      yl) methylsulfinyl]-1H- benzimidazole (E3810) on H+,K(+)-ATPase and gastric acid
      secretion in vitro was investigated, and it was compared with those of omeprazole
      (OPZ). E3810 concentration-dependently inhibited the H+,K(+)-ATPase activity of
      hog gastric vesicles. Its IC50 was 0.26 microM at pH 6.1. The inhibition was
      irreversible in nature and reversed by dithiothreitol. The potency of E3810 was
      10-times that of omeprazole. Acidification of the intravesicular (luminal) space
      increased 1000-fold the potency of E3810, indicating that E3810 is a specific
      inhibitor which binds to the luminal cysteine residue of H+,K(+)-ATPase.
      Prolonged incubation of up to 180 min in the absence of thiol reagents of rabbit
      gastric glands which had been inhibited by a low concentration of E3810 (0.3 and
      0.5 microM) time-dependently and completely reversed the inhibition, as
      determined by aminopyrine uptake, whereas it did not recover the acid secretion
      in omeprazole-treated glands. These results suggest that the acid-activated E3810
      is a potent specific inhibitor of H+,K(+)-ATPase, and that the duration of the
      inhibitory action of E3810 is much shorter than that of omeprazole in isolated
      gastric glands.

PMID- 8282271
TI  - [Analgesic effect of benzoylmesaconine].
AB  - "Tsumura Shuchi-Bushi Powder for Ethical Dispensing" (TJ-3021) is an herbal drug
      of processed Aconiti tuber that attenuates its toxicity. A greater part of
      mesaconitine which is regarded as a main analgesic component in processed Aconiti
      tuber is hydrolyzed into benzoylmesconine (BM) by its processing. In this study,
      the analgesic effect of BM was examined in comparison with that of TJ-3021 in
      mice and rats. BM (10 mg/kg, p.o.) depressed the acetic acid-induced writhing
      significantly. Its analgesic activity was almost similar in magnitude to that of
      TJ-3021 (300 mg/kg, p.o.). BM (30 mg/kg, p.o.) significantly increased the pain
      threshold ratio of paw pressure in repeated cold stress (RCS) rats, and its
      analgesic potency appeared to be equivalent to that of TJ-3021 (1000 mg/kg,
      p.o.). These results suggest that the analgesic activity of BM is strong enough
      for explanation of the analgesic effect of TJ-3021, and it might contribute to
      that of TJ-3021.

PMID- 8282272
TI  - [The prolongation effect on the duration of pentobarbital anesthesia by
      submaxillariectomy in male rats].
AB  - The present study was performed to investigate the effects of submaxillariectomy
      (Subx) on the anesthetic effect (sleeping time) of pentobarbital, the
      concentration-time profile of plasma pentobarbital and the hepatic drug
      metabolizing enzyme systems in male rats of the Donryu strain. Subx was performed
      when the rats were 60 days old. Subx prolonged the duration of pentobarbital (30
      mg/kg, i.p.) anesthesia at 10, 23 and 43 days after the operation, respectively.
      At 43 days after Subx, the plasma pentobarbital concentration was higher in the
      Subx group until 30 min after the administration. There was no significant
      difference in the hepatic microsomal cytochrome P-450 content between the Subx
      and control groups. Cytochrome b5 content, aminopyrine N-demethylase and aniline
      hydroxylase activities were increased significantly in the Subx group. The
      activity of heme oxygenase, the rate limiting enzyme in the heme catabolic
      pathway, tended to increase in the Subx group. Furthermore, the activity of delta
      aminolevulinic acid synthetase, the rate limiting enzyme in the heme synthetic
      pathway, was significantly decreased to 51 percent of the control group by Subx.
      These results may suggest that the prolongation of the duration of pentobarbital
      anesthesia is caused by Subx due to the change in the pharmacokinetics of
      pentobarbital, especially the inhibitory effects of the hepatic pentobarbital
      metabolizing enzyme system.

PMID- 8282273
TI  - [Effect of CV-4151 on the cerebral hypoperfusion and production of thromboxane A2
      following complete cerebral ischemia-reperfusion in dogs].
AB  - The effects of CV-4151 on post-ischemic brain hypoperfusion and thromboxane
      (Tx)A2 production in a canine model of total global brain ischemia were studied.
      Complete cerebral ischemia for 5 min was produced in adult mongrel dogs by
      temporary ligation of the venae cavae and aorta. In the non-treated group,
      cerebral blood flow (CBF) increased during the first 20 to 30 min post-ischemia
      followed by a gradual decline and then stayed below preischemic level; CBF at 2
      hr after the reperfusion was significantly reduced to ca 77% of the pre-ischemic
      level. Water content in the cerebral cortex at 2 hr after the reperfusion in the
      non-treated group was 78.15 +/- 0.21%, higher than the content in the control
      group, 76.70 +/- 0.07%. The concentration of TxB2 in the sagittal sinus was
      significantly increased at 30 min post ischemia. CV-4151 (1.0 mg/kg, i.v.) almost
      completely inhibited the post-ischemic hypoperfusion, significantly inhibited the
      increase in water content and almost completely inhibited the production of TxB2
      in the post-ischemic period and increased the production of 6-keto PGF1 alpha.
      OKY-046 (10 mg/kg, i.v.) had no significant effects on both post-ischemic
      hypoperfusion and increase in water content in the cerebral cortex. We conclude
      that CV-4151 ameliorates post-ischemic cerebral hypoperfusion and that this
      improvement is associated with decreased sagittal sinus levels of TxB2.

PMID- 8282274
TI  - Reproductive and neurobehavioural effects of phloxine administered to mice.
AB  - The colour additive phloxine was given in the diet to provide dietary levels of 0
      (control), 0.1, 0.3 and 0.9%, from 5 wk of age of the F0 generation to 8 wk of
      age of the F1 generation in mice, and selected reproductive and neurobehavioural
      parameters were measured. There was little effect of phloxine on either litter
      size or weight, or sex ratio, whereas the body weight of the pups in the
      lactation period was significantly increased in all treatment groups. Among the
      neurobehavioural parameters measured, surface righting at postnatal day 4 of male
      pups was significantly reduced in all treatment groups. Some parameters of the
      motor activity of pups at 3 wk of age differed from those of the controls; in
      particular, the average speed of movement male pups was significantly reduced in
      all treatment groups. The dose levels of phloxine in this study produced a few
      adverse effects in reproductive and neurobehavioural parameters in mice.

PMID- 8282275
TI  - Monosodium L-glutamate: a double-blind study and review.
AB  - 71 healthy subjects were treated with placebos and monosodium L-glutamate (MSG)
      doses of 1.5, 3.0 and 3.15 g/person, which represented a body mass-adjusted dose
      range of 0.015-0.07 g/kg body weight before a standardized breakfast over 5 days.
      The study used a rigorous randomized double-blind crossover design that
      controlled for subjects who had MSG after-tastes. Capsules and specially
      formulated drinks were used as vehicles for placebo and MSG treatments. Subjects
      mostly had no responses to placebo (86%) and MSG (85%) treatments. Sensations,
      previously attributed to MSG, did not occur at a significantly higher rate than
      did those elicited by placebo treatment. A significant (P < 0.05) negative
      correlation between MSG dose and after-effects was found. The profound effect of
      food in negating the effects of large MSG doses was demonstrated. The common
      practice of extrapolating food-free experimental results to 'in use' situations
      was called into question. An exhaustive review of previous methodologies
      identified the strong taste of MSG as the factor invalidating most 'blind' and
      'double-blind' claims by previous researchers. The present study led to the
      conclusion that 'Chinese Restaurant Syndrome' is an anecdote applied to a variety
      of postprandial illnesses; rigorous and realistic scientific evidence linking the
      syndrome to MSG could not be found.

PMID- 8282276
TI  - Carcinogenicity study of 1,1-bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane in
      B6C3F1 mice.
AB  - 1,1-Bis(tert-butylperoxy)-3.3.5-trimethylcyclohexane (BBTC) is widely used in the
      manufacture of rubber. The present carcinogenicity study in B6C3F1 mice was
      carried out in order to assess its potential to induce tumours. BBTC was
      administered at dietary levels of 0 (control), 0.25 and 0.5% for 78 wk; these
      dose levels were selected on the basis of a subchronic toxicity study, in which
      body weights were depressed to less than 90% of the control group values and
      swelling of hepatocytes was histologically evident in animals fed 1% BBTC or more
      in the diet. Neoplasms were found in all groups, including the control group, but
      there were no significant differences between groups of either sex in mortality,
      tumour incidences or tumour distribution. All tumours were considered to be
      spontaneous because of the similarity to background data for B6C3F1 mice. This
      study thus provides no evidence of carcinogenicity of BBTC in B6C3F1 mice.

PMID- 8282277
TI  - A 91-day feeding study in rats with caprenin.
AB  - Caprenin, a randomized triglyceride primarily comprising caprylic (C8:0), capric
      (C10:0), and behenic (C22:0) acids, was administered in a semi-purified diet to
      weanling Sprague-Dawley rats (25/sex/group) at dose levels of 5.23, 10.23 or
      15.00% (w/w) for 91 days. Corn oil was added at 8.96, 5.91 and 3.00%,
      respectively, to provide essential fatty acids and digestible fat calories. Corn
      oil alone (12.14%) and a blend of medium-chain triglyceride (MCT) oil plus corn
      oil (11.21 and 3.13%, respectively) served as controls. All diets were formulated
      to provide about 4000 kcal/kg of diet and 26.8% of digestible calories from fat
      by assuming that corn oil, MCT oil, and caprenin provided 9, 7 and 5 kcal/g,
      respectively. Survival, clinical signs, body weight, feed consumption, feed
      efficiency, organ weights, organ-to-body-weight ratios, organ-to-brain-weight
      ratios, haematological values and clinical chemistry parameters were evaluated in
      all groups. Histopathology of a full complement of tissues was evaluated in the
      corn oil and MCT oil control groups as well as the high-dose caprenin group.
      Additional rats (n = 5/sex/group) were included in the study to determine whether
      there was marked storage of C22:0 in heart, liver or perirenal fat at the end of
      the 91-day feeding period. No significant differences in body weight gain were
      measured with the balanced caloric diets, although feed conversion efficiency was
      reduced in the high-dose caprenin group. No adverse effects from the ingestion of
      caprenin were detected, nor were significant amounts of C22:0 present in the fat
      extracted from the selected fat depot sites. These results establish a no
      observable-adverse-effect level (NOAEL) of more than 15% (w/w) caprenin in the
      diet (or more than 83% of total dietary fat), which is equal to a mean exposure
      level of more than 13.2 g/kg/day for male rats and more than 14.6 g/kg/day for
      female rats.

PMID- 8282278
TI  - Effect of coffee drinking on cell proliferation in rat urinary bladder
      epithelium.
AB  - A possible effect of freshly brewed drip coffee on urinary bladder carcinogenesis
      was investigated in male Wistar rats using cell proliferation in urinary bladder
      epithelium as the indicator of tumour promotion. Male rats were given either
      undiluted coffee brew (100% coffee), coffee diluted 10 times (10% coffee) or tap
      water (controls), as their only source of drinking fluid for 2 or 6 wk. Uracil,
      known to induce cell proliferation in urinary bladder epithelium, was included in
      the study as a positive control. In rats receiving 100% coffee, body weights,
      liquid intake and urinary volume were decreased. Neither histopathological
      examination of urinary bladder tissue nor the bromodeoxyuridine labelling index
      revealed biologically significant differences between rats receiving coffee and
      the tap water controls. Uracil increased the labelling index and induced
      hyperplasia of the urinary bladder epithelium, as expected. It was concluded that
      these results produced no evidence that drinking coffee predisposes to tumour
      development in the urinary bladder.

PMID- 8282279
TI  - Foetal development in rats fed AIN-76A diets supplemented with excess calcium.
AB  - This study was designed to evaluate the developmental effects of moderate dietary
      calcium increases in rats fed nutritionally adequate diets. Female Charles River
      CD/VAF Plus rats were given 0.50 (control), 0.75, 1.00 or 1.25% dietary calcium
      as calcium carbonate in AIN-76A diets for 6 wk before mating, during mating and
      for 20 days of gestation. On gestation day 20, the animals were killed and
      caesarean sections were performed. Both the non-pregnant and pregnant rats in the
      0.75, 1.00 and 1.25% groups ate slightly more than did the control group during
      most of the intervals measured, but not all the increases were statistically
      significant. There was no consistent pattern of increase or decrease in weight
      gain. No dose-related changes were found in maternal clinical findings, the
      average number of implantations, resorptions and viable foetuses, or foetal
      length or weight. Under the conditions of the study, there were no statistically
      significant increases as compared with the control group in the litter incidence
      regarding specific external, visceral or skeletal variations of the foetuses.
      Dietary calcium was neither foetotoxic nor teratogenic at the concentrations
      used.

PMID- 8282280
TI  - Effect of pretreatment with some mixed-function oxidase enzyme inducers on the
      acute hepatotoxicity of coumarin in the rat.
AB  - Male Sprague-Dawley rats were pretreated with saline, corn oil, sodium
      phenobarbitone (PB) (100 mg/kg body weight/day), 20-methylcholanthrene (20 MC)
      (20 mg/kg body weight/day) or Aroclor 1254 (ARO) (100 mg/kg body weight/day) by
      daily ip injections for 5 days. Animals were then given single oral doses of
      either 250 or 500 mg coumarin/kg body weight and hepatotoxicity was assessed
      after 24 hr. Coumarin produced hepatotoxicity, which comprised hepatocyte
      necrosis and elevation of plasma alanine aminotransferase and aspartate
      aminotransferase activities, in all pretreated groups. Hepatic microsomal
      cytochrome P-450 levels were reduced after coumarin administration. In rats
      pretreated with saline, corn oil or PB, coumarin produced centrilobular hepatic
      necrosis, whereas in rats pretreated with 20 MC or ARO, coumarin produced
      periportal hepatic necrosis. These results demonstrate that mixed-function
      oxidase enzyme inducers can modulate acute coumarin-induced hepatotoxicity in the
      rat. As coumarin is known to be bioactivated by cytochrome P-450-dependent
      enzymes, the change in the lobular distribution of toxicity after pretreatment
      with 20 MC or ARO is presumably due to the induction of particular cytochrome P
      450 isoenzymes in periportal hepatocytes.

PMID- 8282281
TI  - Influence of oxidized deep-frying fat and iron on the formation of food mutagens
      in a model system.
AB  - The effects of oxidized fats, iron and tocopherol content on the yield and
      species of mutagenic heterocyclic amines were studied using a model system. A
      mixture of glycine (0.9 mmol), creatinine (0.9 mmol) and glucose (0.45 mmol) was
      heated for 10 and 30 min at 180 degrees C, with the addition of iron and fats.
      The mutagens formed were identified and quantified using HPLC. (2-Amino-3
      methylimidazo[4,5-f]-quinoxaline) (IQx), 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8
      DiMeIQx) were formed in the model mixtures. The addition of iron (FeSO4) or
      oxidized fats to the model system did not affect the species of food mutagens
      formed, but the iron addition more than doubled the amount of MeIQx. The
      oxidation status of the fat added to the model system had little effect on the
      formation of MeIQx. The fat content was shown to affect the mutagen formation
      significantly, especially after heating for 30 min. No difference in yield of
      MeIQx was observed in the presence of tocopherol and tocotrienol at naturally
      occurring concentrations.

PMID- 8282282
TI  - Analysis of commercial bouillons for trace levels of mutagens.
AB  - A new method, developed specifically for the extraction of heterocyclic aromatic
      amine (HAA) type mutagens from different food matrices, was applied to various
      forms of commercially available bouillons. This procedure is based on liquid
      liquid extraction of the sample at different pH values. Recovery and
      reproducibility of the procedure was determined by processing spiked samples
      using a mutagenicity bioassay technique as an endpoint. The mutagenicity was
      tested in the Salmonella/microsome assay using strain TA98 with metabolic
      activation. 22 bouillon samples in liquid, cube or powder forms from seven
      manufacturers were extracted and tested for potential mutagenicity. The mutagenic
      activity of these samples varied and ranged from non-detectable to about 1200
      induced revertants per gram of solid material, with a median value of
      approximately 250 revertants/g. The mutagenic response appeared to be dependent
      on the source rather than the type or form of the product tested. A negative
      response was obtained from only one chicken bouillon, and the highest positive
      response was obtained from a beef bouillon in cube form. It appears that the
      average beef sample, regardless of form, has a higher mutagenic potency than
      chicken or chicken and turkey samples. Overall, the intake of mutagens from
      commercial bouillons (obtained as cubes, concentrates or dry mixes) to prepare
      one serving (as bouillon, soup, casseroles, etc.) is considerably less than that
      reported in the literature for one serving of fried beef or pork. The
      extractability and mutagenic characteristics of these samples indicate the
      presence of HAA-type mutagens. Work is in progress to identify the mutagenic
      factors in bouillons.

PMID- 8282283
TI  - Genotoxicity of nitrosated red wine and of the nitrosatable phenolic compounds
      present in wine: tyramine, quercetin and malvidine-3-glucoside.
AB  - Phenolic compounds and biogenic amines are known to be present in some foodstuffs
      which become directly genotoxic after nitrosation in vitro. Red wine has
      previously been shown to be genotoxic and this activity has been attributed
      mainly to flavonoids. Besides flavonoids, red wine contains a multiplicity of
      compounds, including biogenic amines. Using the Ames assay and the SOS
      chromotest, this study has shown that red wine and some of the nitrosatable
      molecules present in wine become directly genotoxic on nitrosation in vitro:
      these include the phenolic molecules tyramine, quercetin and malvidine-3
      glucoside, whereas phenylethylamine and histamine were negative on nitrosation.
      Interestingly, quercetin had been predicted to be negative after nitrosation,
      using the CASE methodology. The concentrations of these three positive
      nitrosatable compounds in wine were determined by HPLC. Comparison of these
      concentrations and their respective levels of genotoxicity suggests that the
      genotoxicity after nitrosation is probably attributable to other molecules. It is
      also possible that synergistic effects may occur between various nitrosatable
      compounds in wine.

PMID- 8282284
TI  - Levels of fumonisin B1 in corn naturally contaminated with aflatoxins.
AB  - Aflatoxins and fumonisin B1 are hepatotoxic and carcinogenic metabolites produced
      by Aspergillus flavus and Fusarium moniliforme, respectively. These fungi are
      common natural contaminants of corn, and both aflatoxins and fumonisin B1 have
      been implicated as aetiological agents in animal and human diseases. To determine
      whether these mycotoxins co-exist on corn under natural conditions, 28 samples
      from the 1991 Georgia (USA) corn crop were assayed for (total) aflatoxin and
      fumonisin B1. 27 samples were positive for aflatoxin, 24 samples were positive
      for fumonisin B1, and 23 samples had detectable levels of both. In the positive
      samples, the mean aflatoxin concentration was 73 ppb (SD = 86), and the average
      fumonisin B1 concentration was 0.87 ppm (SD = 0.65). A correlation between
      aflatoxin and fumonisin B1 concentrations was not evident. None the less, these
      results demonstrate that exposure to both mycotoxins can occur simultaneously by
      consumption of co-contaminated corn.

PMID- 8282285
TI  - Safety evaluation of esperase.
AB  - Esperase is a proteolytic enzyme preparation that can be used as a processing aid
      in the food industry. The following studies were performed to establish safety
      for the consumer: oral toxicity study (13 wk) in the rat; teratogenicity study in
      the rat; gene mutation assays in Salmonella typhimurium and mammalian cells in
      vitro, and chromosome aberration assay in vitro. General toxicity was low; the
      effects seen were attributed to proteolytic activity and the loading with sodium
      chloride. Neither of these factors will be relevant to consumers of the processed
      food. There was no evidence of effects on pregnancy outcome or mutagenic
      potential. When these results are considered together with existing knowledge of
      the production organism and the chemical and microbiological characterization of
      the enzyme preparation, they indicate that Esperase will be safe for its intended
      application in food processing.

PMID- 8282286
TI  - [Neurosurgical therapy of subarachnoid hemorrhage. Microsurgical techniques-
      early postoperative nimodipine administration].
AB  - With the increasing life expectancy of the general population, the number of
      geriatric patients with aneurysmatic subarachnoid bleeding consulting the
      neurosurgeon is also increasing. The possibilities of modern micro-neurosurgery
      have created a situation that permits craniotomy and aneurysmal clipping in the
      geriatric patient with an acceptably low level of risk and high probability of
      high post-operative quality of life. Although a definitive evaluation of
      perioperative administration of calcium channel blockers in geriatric patients
      with an aneurysm is not yet possible, experience so far gained points to their
      positive effect on a more rapid and more pronounced resolution of the post
      hemorrhagic impairment of the cognitive performance.

PMID- 8282287
TI  - [Therapy of dementing diseases: value of calcium antagonists].
AB  - The possibilities and limitations of treatment of dementia with nootropic agents
      are discussed. Particular attention is directed to the calcium antagonist,
      nimodipine, with its demonstrably excellent efficacy. Treatment with nootropic
      agents should be initiated after meticulous establishment of the diagnosis of
      dementia and continued over the long-term, if their effectiveness is clinically
      manifest.

PMID- 8282288
TI  - [Pharmacokinetics and -dynamics of calcium antagonists in the elderly].
AB  - The therapeutic effect of a drug is determined by various properties and
      parameters. Both dose and pharmacodynamics determine the amount of active agent
      or its metabolites--and thus their effects--at the site of action. With
      increasing age, both pharmacodynamics and pharmacokinetics can change.
      Differences in action in old age may be due to changes in the number and
      sensitivity of binding sites or to other physiological changes associated with
      aging. Pharmacokinetics processes (clearance, distribution) are commonly affected
      by aging. Clinico-pharmacological studies involving calcium antagonists, for
      example verapamil, diltiazem and nifedipine, have been performed in the elderly
      by a number of authors.

PMID- 8282289
TI  - [Weight reduction with alternative diets. 9: Alternative diets (R)].

PMID- 8282290
TI  - [Monotherapy of mild to moderate hypertension. Double-blind comparative study:
      amlodipine versus enalapril].
AB  - METHODS: A double-blind multicenter study involving 89 patients with mild-to
      moderate essential hypertension was performed to compare the efficacy and
      tolerability of amlodipine and enalapril. Following a placebo-controlled run-in
      phase, treatment was initiated with a daily dose 5 mg amlodipine or enalapril. In
      the second week of treatment, the daily dose of enalapril was increased to 10 mg.
      After two weeks of treatment, the amlodipine dose was increased from 5 to 10 mg,
      the enalapril dose from 10 to 20 mg if the diastolic seated blood pressure
      exceeded 90 mmHg. RESULTS: Mean systolic and diastolic blood pressures decreased
      in the amlodipine group from, respectively, 158 +/- 17/101 +/- 6 mmHg to 142 +/-
      14/87 +/- 11 mmHg, and in the enalapril group from 157 +/- 15/102 +/- 5 mmHg to
      140 +/- 16/88 +/- 12 mmHg. The reduction in blood pressure was statistically
      significant in both groups (p < 0.0001), but the difference in blood pressure
      lowering effect of the two treatments was not statistically significant. The
      target blood pressure (diastolic BP seated < 90 mmHg) was achieved in 24 patients
      (75%) in the amlodipine group, and 23 patients (68%) in the enalapril group.
      Neither group experienced any severe adverse reactions. Side effects were seen in
      3 patients of the amlodipine group and in 6 of the enalapril group.

PMID- 8282291
TI  - A population-based study of syphilis and sexually transmitted disease syndromes
      in north-western Tanzania. 1. Prevalence and incidence.
AB  - OBJECTIVE: To determine the prevalence of syphilis and the prevalence and
      incidence of self-reported STD syndromes in the population of Mwanza Region,
      North-Western Tanzania. METHODS: A population-based random cluster sample survey,
      stratified by rural, roadside or urban residence, of 4173 individuals aged 15-54
      years was performed in 1990-91. The seroprevalence of syphilis (using TPHA and
      RPR) and the prevalence and incidence of self-reported genital ulcer syndrome
      (GUS) and genital discharge syndrome (GDS) were determined. RESULTS: Active
      syphilis was detected in 9% of the adult population, while 15% had serological
      evidence of past or current infection. Seroprevalence was significantly lower in
      the rural than in the roadside and urban populations, but there was little
      difference between men and women. Amongst men, a history of GDS was reported by
      28%, and a history of GUS by 14%, with point prevalences of 2.3% and 1.3%
      respectively. Annual incidence among men were 6.8% for GDS and 3.6% for GUS.
      Women reported these conditions less frequently. There was little difference
      between the strata in the prevalence or incidence of reported STD syndromes.
      CONCLUSION: Sexually transmitted diseases represent a major public health problem
      in both the rural and urban populations of Mwanza Region.

PMID- 8282292
TI  - A population-based study of syphilis and sexually transmitted disease syndromes
      in north-western Tanzania. 2. Risk factors and health seeking behaviour.
AB  - OBJECTIVE: To determine risk factors for syphilis and sexually transmitted
      disease (STD) syndromes, and to study health seeking behaviour among those with
      STD syndromes, in the population of Mwanza Region, North-Western Tanzania.
      METHODS: A population-based random cluster sample survey, stratified by rural,
      roadside or urban residence, of 4173 individuals aged 15-54 years was performed
      in 1990-91. The seroprevalence of syphilis and the prevalence and incidence of
      self-reported genital ulcer syndrome (GUS) and genital discharge syndrome (GDS)
      are reported in the accompanying paper. This paper reports on risk factors for
      these conditions and on health seeking behaviour among those reporting them.
      RESULTS: In both sexes, the risk of STDs increased with the reported number of
      sexual partners in the previous five years. Men who were separated, divorced or
      widowed were at increased risk of STDs, but this was not the case among women.
      Higher educational status was associated with an increased risk of urethral
      discharge in males but with a decreased prevalence of syphilis in females. Male
      circumcision was associated with an increased risk of urethral discharge but a
      reduced prevalence of syphilis. Nearly all men, and 90% of women, reporting
      symptoms of genital discharge or ulceration had sought treatment. Of these,
      approximately 70% of males and 60% of females had sought treatment in the
      official health sector. CONCLUSIONS: Targetted health education concerning risk
      reduction for HIV infection and other STDs should be a high priority in this
      population. Improved case management of STDs in health centres and dispensaries
      may have a substantial impact on the incidence of these infections.

PMID- 8282293
TI  - High prevalence of sexually transmitted diseases in a rural area in Mozambique.
AB  - OBJECTIVE: To assess the extent of the sexually transmitted diseases (STDs)
      problem in a rural area of Mozambique. METHODS: A cross sectional study among
      pregnant women and patients presenting with genital complaints. Laboratory
      confirmation was done for gonorrhoea, chlamydial infection, active syphilis,
      trichomoniasis and HIV infection. SETTING: A primary health care setting in
      Vilanculos, Inhambane province, Mozambique. RESULTS: Evidence of one or more of
      the above STDs was found in 51% of 201 pregnant women, 56% of 85 women and 62% of
      77 men with genital complaints. Neisseria gonorrhoea or Chlamydia trachomatis
      were found in 16% of pregnant women, 23% of female patients and 28% of male
      patients; genital ulcer disease was present in 6%, 28% and 36%, of respectively
      pregnant women, female and male patients. The prevalence of active syphilis was
      about the same in the three groups of study subjects, that is 15%. HIV infection
      was found in 4% of the male patients; no HIV infection could be detected in the
      female groups. CONCLUSION: STDs were a major health problem in this rural area in
      Mozambique. Though HIV infection was still low, the high prevalence of STDs
      indicates that the potential is there for an explosive spread of the HIV/AIDS
      epidemic.

PMID- 8282294
TI  - Prevalence of syphilis infection in Mozambican women with second trimester
      miscarriage and women attending antenatal care in second trimester.
AB  - OBJECTIVES: To elucidate whether recent syphilis infection is significantly more
      prevalent among women with mid-trimester miscarriage than among antenatal care
      attenders in midtrimester pregnancy. DESIGN: Two categories of pregnant women
      were compared regarding serological signs of syphilis. Rapid Plasma Reagin (RPR)
      analyses were done in Mozambique and Veneral Disease Research Laboratory (VDRL)
      tests in Sweden. In case of RPR and/or VDRL positivity, Treponema pallidum
      haemagglutination (TPHA) and Captia Syphilis-M were performed. SETTING: A
      suburban antenatal care clinic and the emergency ward at the Department of
      Obstetrics and Gynecology at the Central Hospital in Maputo, Mozambique, were
      studied June-August 1991. SUBJECTS: Randomly selected women seeking antenatal
      care in midtrimester pregnancy (N = 202) were compared with 114 women
      consecutively entering with clinical signs of midtrimester miscarriage. RESULTS:
      Among antenatal care attenders, 37/202 (18.3%), and among women with midtrimester
      miscarriage, 37/114 (32.5%), had syphilis confirmed with the Treponema pallidum
      haemagglutination test (p < 0.01). Significant titres of IgM antibodies tended to
      be more prevalent among women with miscarriage (7.0%) than among women attending
      antenatal care (4.5%), though the difference only approached statistical
      significance. CONCLUSION: The findings suggest a potential association between
      syphilis seropositivity and midtrimester miscarriage. Present findings justify
      more extensive studies to establish whether or not recent syphilis infection is a
      risk factor for midtrimester miscarriage.

PMID- 8282295
TI  - Sexually transmitted diseases reported by STD services in The Netherlands, 1984
      1990.
AB  - OBJECTIVE: To present general trends in sexually transmitted disease (STD) in the
      Netherlands during the period 1984-1990 and to describe characteristics of the
      patients in order to get insight into possible factors underlying these trends.
      METHODS: Since 1984 patients diagnosed with STD visiting STD clinics and local
      public health services in the Netherlands are reported by the nursing staffs. In
      addition to diagnosis and gender of the patient epidemiological background
      information is registered. The reported annual cases of gonorrhoea, syphilis and
      Chlamydia trachomatis infections are presented. Further, the epidemiological
      features of over 25,000 patients with infections due to Chlamydia trachomatis,
      gonorrhoea or syphilis infections were compared. RESULTS: During the period 1984
      1990 an overall decrease in the total number of gonorrhoea infections was
      reported; among homosexual males; however, an increase in gonorrhoea rates and an
      increasing number of sexual partners after 1989 was reported. Furthermore, the
      percentage of gonorrhoea infections caused by penicillinase-producing Neisseria
      gonorrhoeae was found to be on the increase in various subgroups but not in
      homosexual males. Syphilis rates among females declined from 1984 to 1987 after
      which an increase was reported reaching a peak in 1989; syphilis rates among
      males peaked during 1989. After 1988 Chlamydia trachomatis infections increased
      which, however, is largely due to the introduction of screening among all
      visitors of the Amsterdam STD service resulting in improved case-detection.
      Finally, it appeared that STDs are not randomly distributed over the population
      but are associated with certain patient characteristics. CONCLUSION: The data
      provided by STD services reveal an epidemiological pattern for STDs in the
      Netherlands. The increase in the reported number of gonorrhoea infections among
      homosexuals together with the increasing number of sexual partners among
      homosexual males suggest that a group of highly sexually active individuals
      switch or return to higher risk behaviours. Further research is needed to
      determine the causes of the described trends and behavioural changes in order to
      undertake preventive activities.

PMID- 8282296
TI  - Women with HIV presenting at three London clinics between 1985-1992.
AB  - OBJECTIVE: To determine the changing patterns of HIV infection in women in three
      units in London. SUBJECTS: Three hundred and fifty seven HIV seropositive women
      who have attended outpatient clinics between 1984 and 1992. METHODS: A
      retrospective review of data obtained from a computerised database and
      supplemented by direct inspection of the notes. RESULTS: The number of newly
      identified women with HIV has risen steadily over the period of study with a
      significant shift towards a heterosexual mode of transmission. This is a
      reflection of increasing numbers of women from Sub-Saharan Africa rather than a
      rise in the incidence of HIV in women born in the UK. CONCLUSIONS: The increase
      in women infected by HIV remains predominantly restricted to women in "high risk"
      groups. Although encouraging, our data should be interpreted with caution since
      it suffers from the inherent bias of selective testing. Safer sex education and
      epidemiological surveillance should continue despite the apparent low risk to
      women born in the UK.

PMID- 8282298
TI  - Genital human papillomavirus infection among patients attending an STD clinic.
AB  - OBJECTIVES--To determine the prevalence of human papillomavirus (HPV) infection
      in patients, male and female, attending a clinic for sexually transmitted
      diseases (STDs). DESIGN--A randomly selected group of patients representative of
      the population studied and first-time visitors to the STD clinic, were asked to
      participate in the study. Samples from the skin and mucous membranes of the lower
      genital region were taken for cytological analysis by the polymerase chain
      reaction (PCR) method for HPV DNA. The patients then underwent colposcopy or
      peniscopy after acetic acid application. SETTING--Department of Dermatology and
      Venereology, University Hospital, Uppsala, Sweden. SUBJECTS--A total of 131
      patients, 66 women and 65 men, attending the clinic for various reasons. RESULTS-
      At colposcopy/peniscopy, 18 patients (10 men and 8 women) had lesions typical of,
      and 24 (12 men and 12 women) suspicious of HPV infection. With the PCR technique
      HPV DNA was detected in 72% of the patients with typical lesions and in 54% of
      those with suspicious lesions. CONCLUSION--Nearly one-third or 30.5% of these
      randomly selected patients in a Swedish STD clinic were infected by HPV. The
      diagnosis was made by clinical inspection and/or by HPV DNA analysis with PCR.

PMID- 8282297
TI  - A comparison of sexual behaviour and risk behaviour for HIV infection between
      women in three clinical settings.
AB  - OBJECTIVE: To compare sexual behaviour and HIV risk behaviour between women in
      three clinical settings and to investigate the effect of socio-economic status
      and ethnic origin upon these behaviours. SUBJECTS AND METHODS: A questionnaire
      was administered to 1,950 women attending clinics for genitourinary medicine
      (GUM) family planning and termination of pregnancy (TOP), all in inner London.
      RESULTS: A quarter of women attending the GUM and TOP clinics were not using any
      regular form of contraception. Differences in the median numbers of sexual
      partners in the past year (1-2) and over lifetime (4-6) between the three groups
      were slight. Amongst the women in all three groups: more than half (54.8-64.9%)
      had had a non-regular partner in the preceding twelve months; fewer than one
      fifth (10.4-17.1%) reported always using condoms with their regular partners, and
      fewer than two-fifths (31.3-39.7%) always used them with their non-regular
      partners; approximately one in five women (18.6-23.9%) reported one or more major
      HIV risk behaviours. Some parameters of sexual behaviour were found to be
      influenced by socio-economic status and/or ethnic origin. CONCLUSIONS: The
      behaviour of women attending these three clinics is very similar. Women attending
      clinics for family planning or termination of pregnancy need advice on sexually
      transmitted diseases and HIV infection, and women attending genitourinary
      medicine or termination clinics need advice on contraception. Closer integration
      between disciplines is required to provide a comprehensive sexual health service
      for women.

PMID- 8282300
TI  - The effect of suppressive oral acyclovir on the psychological morbidity
      associated with recurrent genital herpes.
AB  - OBJECTIVES: To assess the psychological impact of recurrent genital herpes and to
      determine if longterm acyclovir has any impact on this morbidity. SETTING AND
      SUBJECTS: Patients with frequently recurring genital herpes attending a
      department of genitourinary medicine who were considered suitable for longterm
      acyclovir. METHODS: Patients completed an 80 item, self-administered
      psychological questionnaire before starting acyclovir and every three months for
      one year. Treatment was then stopped and three months later a further
      questionnaire was completed. The questionnaire consisted of the General Health
      Questionnaire (GHQ); the Hospital Anxiety and Depression Questionnaire (HADQ);
      Illness Attitude Scales and Illness Concern. Data were analysed by McNemar's test
      for changes in proportions and by Wilcoxon's test for changes in scores. RESULTS:
      102 patients were recruited: 55 men, and 47 women. Eighty two (80%) patients
      completed three months treatment, 75 (74%) six months, 64 (63%) nine months and
      61 (60%) a year. Fifty (49%) of the original 102 patients completed the three
      months post treatment follow up. At first visit 63% (64/102) were designated as
      GHQ "cases". Within three months this decreased to 26% (21/82). McNemar's test
      showed that 67% (34/51) of the patients who were initially classified as GHQ
      "cases" became "noncases" after three months (p < 0.0001). There was a
      significant decrease in the proportion of HAD anxiety cases from visit one to
      visit two (p < 0.0001) and a decrease in illness concern scores from visit one to
      visit two (p < 0.0001). All these decreases were maintained throughout the years
      treatment with acyclovir. CONCLUSIONS: There is a substantial morbidity
      associated with frequently recurring genital herpes. However, acyclovir
      suppression significantly reduces illness concern and anxiety and is a useful
      addition to the treatment of this infection.

PMID- 8282299
TI  - Changes in HPV infection in patients with anogenital warts and their partners.
AB  - OBJECTIVES--To investigate the relationship between clinical findings and the
      detection of human papillomavirus (HPV) DNA in a range of anatomical sites in
      patients with and without anogenital warts. SUBJECTS--Men and women with a
      clinical diagnosis of anogenital warts, or a current partner with anogenital
      warts. SETTING--A department of genitourinary medicine in central London. METHODS
      -The anogenital areas of the patients were thoroughly examined using a colposcope
      before and after application of acetic acid. Different types of specimens were
      taken from a variety of anatomical sites. Superficial skin sampling was performed
      by the application of slides covered with "Superglue" (SG) to clinically normal
      and abnormal areas of anogenital skin. The presence of human cells in the SG
      samples was confirmed by detection of the beta-globin gene using the polymerase
      chain reaction (PCR). HPV DNA was extracted from the specimens and amplified by
      using consensus primers with the PCR. HPV types 6, 11, 16, 18, 31 and 33 were
      identified by Southern blotting followed by hybridisation. RESULTS--In women, HPV
      DNA was detected in 83% of wart biopsies, 29% of cervical biopsies, 36% of
      cervical scrapes, 25% of urethral loop specimens, 37% of vaginal washes and 33%
      of rectal swab specimens. In men, HPV DNA was detected in 67% of wart biopsies,
      37% of urethral loop specimens and 12% of rectal swab specimens. Of the SG
      samples containing the beta-globin gene, 49% from women and 50% from men
      contained HPV DNA. HPV DNA was not detected in buccal scrapes and serum samples
      from women or men. Of all specimens with detectable HPV DNA, there was evidence
      of a single HPV type in 41%, multiple types in 48% and undetermined types in 11%.
      Samples taken from different sites of a patient tended to have HPV types in
      common. Sexual partners, however, did not consistently have HPV types in common.
      CONCLUSIONS--HPV DNA was distributed widely in the anogenital area, in warts,
      acetowhite areas and clinically normal skin. The SG technique was well tolerated
      by patients and produced results consistent with other findings. Sampling from a
      single site of the genitalia on one occasion may significantly underestimate the
      infection rate with HPV. Multifocal infection of the anogenital area with HPV
      should be taken into consideration when interpreting epidemiological studies and
      management strategies.

PMID- 8282301
TI  - Osteomyelitis presenting as genital sore: a case report.
AB  - A female attending the skin outpatient department presented with a genital sore
      which was treated as chancroid. On further investigation it proved to be the
      opening of a sinus secondary to chronic osteomyelitis of the pubic symphysis.

PMID- 8282302
TI  - Historical account of venereal diseases in Mexico.
AB  - This paper reviews the history of sexually acquired diseases in Mexico. It is
      divided into four major chronological sections which discuss social attitudes and
      values, the development of services and of official policy, and historical
      epidemiology.

PMID- 8282303
TI  - Opportunistic cervical cytology screening in a genitourinary medicine department:
      is it worthwhile?

PMID- 8282304
TI  - Establishing a satellite genitourinary medicine clinic.

PMID- 8282305
TI  - Mixed infections of Chlamydia trachomatis may be missed using nested PCR.

PMID- 8282306
TI  - Positive syphilis test results in Down's syndrome in the past: a contemporary
      explanation.

PMID- 8282307
TI  - Penicillinase producing Neisseria gonorrhoeae associated with severe
      vulvovaganitis in a post menopausal woman.

PMID- 8282308
TI  - Chronic perianal ulcerations: role of Trichomonas vaginalis?

PMID- 8282309
TI  - Small spectrum of prevalent gonococcal auxotype/serovar classes in Africa.

PMID- 8282310
TI  - A challenge to the instructive model of positive selection.

PMID- 8282311
TI  - Positive selection of TcR alpha beta thymocytes: is cortical thymic epithelium an
      obligatory participant in the presentation of major histocompatibility complex
      protein?

PMID- 8282312
TI  - Repertoire-determining role of peptide in the positive selection of CD8+ T cells.

PMID- 8282313
TI  - The role of p56lck and p59fyn tyrosine kinases and CD45 protein tyrosine
      phosphatase in T-cell development and clonal selection.

PMID- 8282314
TI  - The identity of the cells that positively select thymocytes.

PMID- 8282315
TI  - Thymic selection reinterpreted.
AB  - To summarize, I have attempted to present evidence that the unselected thymocyte
      TCR repertoire has such a propensity to recognize MHC/peptide at high affinity
      that it is likely that, were tolerance induction to be invariably dominant over
      positive selection, all T cells would be deleted or anergized. If this is true it
      follows that positive selection must in fact be capable of being the dominant
      process. I have further suggested that the existence of peptides capable of
      antagonizing T-cell activation in the thymus could inhibit deletion, and that
      this might correspond to positive selection.

PMID- 8282316
TI  - Affinity maturation of lymphocyte receptors and positive selection of T cells in
      the thymus.
AB  - In this review we have re-evaluated the dominant paradigm that TcR V genes do not
      somatically mutate. We highlight the many structural and functional similarities
      between Ig and TcR antigen-specific receptors on B and T cells. We have reviewed
      the factors influencing the somatic and germline evolution of IgV regions in B
      cells, have evaluated in detail various models which could be invoked to explain
      the pattern of variation in both transcribed and non-transcribed segments of
      germline IgV-gene DNA sequences, and applied this perspective to the TcR V beta
      and V alpha genes. Whilst specific TcRs recognize a complex of a short antigenic
      peptide bound to MHC Class I or II glycoprotein, and Ig receptors can recognize
      both oligopeptides and conformational determinants on undegraded polypeptides,
      they both employ heterodimer variable regions (Fabs) utilizing all three CDRs in
      epitope binding. We conclude that a plausible case can be made for the
      possibility that rearranged TcR V genes may undergo some type of somatic
      hypermutation process during T-cell development in the thymus (concurrent with or
      after the positive selection phase) thus allowing a repertoire of TvR alpha beta
      heterodimers to be both positively and negatively selected by the same set of
      ligands (self MHC + self peptide) in the thymus.

PMID- 8282317
TI  - The specificity of positive selection: MHC and peptides.

PMID- 8282318
TI  - Positive selection of immature alpha beta T cells.

PMID- 8282319
TI  - Why positive selection?

PMID- 8282320
TI  - Neurogenic component of ouabain-evoked contractions is modulated by the
      endothelium.
AB  - The influence of endothelium on the neurogenic component of ouabain-induced
      contractions in isolated perfused guinea pig carotid arteries was analyzed.
      Ouabain (0.1 mumol/L to 0.1 mmol/L) evoked concentration-dependent increases of
      perfusion pressure. Phentolamine (0.3 to 10 mumol/L) and prazosin (30 nmol/L to
      10 mumol/L) (nonselective antagonist of alpha-adrenergic receptors and selective
      antagonist of alpha 1-adrenergic receptors, respectively) induced a concentration
      dependent relaxation in segments precontracted with ouabain (0.1 mmol/L). When
      the arteries were preincubated with those blockers (both at 3 mumol/L) or the
      animals were pretreated with reserpine, the contractions to the glycoside were
      diminished, indicating that they are partially mediated by norepinephrine release
      from adrenergic nerve endings. De-endothelialization abolished the effect of
      adrenergic blockade on ouabain-induced contractions. On the other hand, de
      endothelialization did not modify significantly the effect of the adrenergic
      blockade on norepinephrine-induced contractions. The nitric oxide blocker
      oxyhemoglobin, at concentrations (10 mumol/L) that abolished endothelium
      dependent relaxations induced by 3 mumol/L acetylcholine; or the cyclooxygenase
      blocker indomethacin (10 mumol/L) did not modify the relaxation caused by
      phentolamine. In bioassay experiments, 30 mumol/L phentolamine induced a
      relaxation on the ouabain-elicited contraction only when the glycoside was added
      through a donor segment with endothelium. Ouabain-induced tritiated
      norepinephrine release was significantly reduced by the removal of endothelium
      but not by 1 mumol/L oxyhemoglobin or 1 mumol/L indomethacin. These results
      suggest that the endothelium modulates the neurogenic component involved in
      contractions evoked by the glycoside by a diffusible factor (or factors) whose
      nature is unknown; however, the factor is neither nitric oxide nor a
      cyclooxygenase-related compound.

PMID- 8282321
TI  - Altered cardiorespiratory transfer in hypertension.
AB  - The effect of continuously slowing respiration (from 0.46 to 0.05 Hz, eg, from 30
      to 3 breaths per minute) on cardiovascular variables was studied in 14
      hypertensive patients and 16 normotensive subjects. Beat-to-beat time-frequency
      (Wigner) distributions were used for dynamic analysis of RR interval and systolic
      and diastolic pressures. Dominant breathing frequency at rest did not differ in
      hypertensive patients from the control group (0.21 versus 0.19 Hz). However, in
      the hypertensive group it was disturbed 34.4% of the time by slow breathing and
      apneas, which evoked transient blood pressure instability and increased spectral
      powers at low frequencies (range, 0.01 to 0.1 Hz). The nonrespiratory
      fluctuations (NONRFs) and respiratory fluctuations (RFs) in RR interval and
      NONRFs in systolic pressure were smaller in hypertensive patients (P < .001). In
      both groups, slowing of respiratory frequency from 0.46 to 0.05 Hz entrained RFs
      in the RR interval and systolic and diastolic pressures. RFs in the RR interval
      remained diminished in hypertensive patients (P < .001), but RFs in systolic
      pressure increased higher at maximum, corresponding to breathing frequencies from
      0.07 to 0.09 Hz (P < .001). A dynamic cardiorespiratory index (ratio of RFs in RR
      interval and systolic pressure) was smaller (P < .01) in hypertensive patients
      than in normotensive subjects. Irregular breathing at rest was found in
      hypertensive patients. The transfer from respiration into RR interval was
      diminished, suggesting an impaired parasympathetic responsiveness in mild
      hypertension.

PMID- 8282322
TI  - Combination treatment of enalapril with nitrendipine in rats with renovascular
      hypertension.
AB  - We have recently shown that treatment with the calcium channel blocker
      nitrendipine may aggravate albuminuria and glomerular injury in rats with two
      kidney, one clip renovascular hypertension if arterial blood pressure is not
      reduced. To test whether nitrendipine also exerts its adverse renal effects when
      normotension is achieved, we examined the effect of combined therapy with
      nitrendipine and the converting enzyme inhibitor enalapril on blood pressure,
      albuminuria, glomerular filtration rate, and morphology of the nonclipped kidney.
      Rats treated with enalapril alone or in combination with the diuretic
      hydrochlorothiazide or rats treated with nitrendipine alone served as controls.
      Therapy was started 6 weeks after clipping of one renal artery. Nitrendipine
      alone did not reduce blood pressure but significantly increased albuminuria,
      diuresis, glomerular filtration rate, and glomerular volume and injury compared
      with untreated hypertensive controls. Increase of glomerular filtration rate,
      diuresis, and albuminuria was reversible after withdrawal of nitrendipine.
      Treatment with enalapril alone decreased blood pressure significantly but not to
      normotensive levels and was without significant effect on albuminuria and
      glomerular morphology. The combination of nitrendipine and enalapril reduced
      blood pressure to normotensive levels and not only prevented the increase of
      glomerular volume, glomerular filtration rate, diuresis, and albuminuria caused
      by nitrendipine alone but furthermore improved glomerular injury and albuminuria
      to levels not significantly different from normotensive controls. Enalapril in
      combination with the diuretic had similar beneficial effects on blood pressure,
      albuminuria, and glomerular injury. These data demonstrate that the adverse
      effects of nitrendipine monotherapy on glomerular structure and function can be
      prevented by the combination of nitrendipine and enalapril when blood pressure is
      normalized.

PMID- 8282323
TI  - Effects of fludrocortisone on sympathetic nerve activity in humans.
AB  - Fludrocortisone reduces plasma norepinephrine in healthy humans, but forearm
      vascular and pressor responses to norepinephrine are potentiated. The effects of
      fludrocortisone on sympathetic nerve activity in healthy humans are not known. To
      investigate these effects we evaluated muscle sympathetic nerve activity, heart
      rate, and arterial pressure in 11 healthy volunteers during three protocols: (1)
      before and on day 7 of fludrocortisone (0.4 mg/d) treatment with ad libitum diet
      (n = 6); (2) before and on day 7 of fludrocortisone (0.4 mg/d) or placebo with a
      150 mmol/24 h (mEq/24 h) sodium diet (n = 7); and (3) before and on day 2 of
      fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet
      (n = 4). Placebo did not alter any parameter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282324
TI  - Pathophysiology and management of hypertension in acute ischemic stroke.

PMID- 8282325
TI  - Distribution of type 1 angiotensin II receptor subtype messenger RNAs in the rat
      fetus.
AB  - The localization of the two type 1 angiotensin II receptor subtype (AT1A and
      AT1B) messenger RNAs in the 19-day-old rat fetus was studied by in situ
      hybridization. AT1 receptor mRNAs were detected in target organs of the renin
      angiotensin system such as the kidney, adrenal gland, liver, heart, large
      arteries, and pituitary gland. In addition, angiotensin II receptors were present
      in specialized mesenchymal cells surrounding the cartilage, in the pericardium,
      in the lung, and in the undifferentiated mesenchymal tissue. The AT1A subtype was
      predominant in all tissues and organs except the adrenal cortex and glomeruli in
      the kidney, which expressed both AT1A and AT1B mRNAs. The widespread distribution
      of AT1 receptors in tissues and organs involved in hydromineral equilibrium and
      blood pressure regulation shows that during fetal development angiotensin II may
      already act as a regulator of the cardiovascular system. An effect on cellular
      differentiation and/or proliferation via AT1 receptors is also suggested by their
      location in several mesenchymes.

PMID- 8282326
TI  - Short-term variability of blood pressure and heart rate in borderline and mildly
      hypertensive subjects.
AB  - Electrocardiogram and intra-arterial blood pressure were recorded in 96 men (aged
      35 to 45 years) by the Oxford method over a 30-hour period. The study involved 33
      normotensive, 29 borderline hypertensive, and 34 mildly hypertensive individuals,
      as assessed by the cuff method. Five-minute periods during sleep and with
      subjects in supine, sitting, and standing positions were extracted from the
      recordings for frequency domain analysis. Power spectrum density estimates of
      systolic blood pressure, diastolic blood pressure, and heart rate were calculated
      by an autoregressive method over the bandwidths of 0.02 to 0.075 (low-frequency),
      0.075 to 0.15 (midfrequency), and 0.15 to 0.35 Hz (high-frequency), attributable
      to thermoregulatory, baroreceptor, and respiratory activity. No significant
      intergroup differences were observed at nighttime, but in different body
      positions the borderline hypertensive subjects frequently had either greater low
      frequency variability or smaller midfrequency variability than the other groups.
      In this respect, the power spectra for systolic and diastolic blood pressures
      provided better statistical differentiation between the groups than those for
      heart rate. Furthermore, the borderline hypertensive subjects exhibited
      attenuated night-day changes in the low-frequency band for all time series. The
      results suggest that in borderline hypertension the baroreceptor oscillations are
      shifted to lower frequencies, presumably reflecting altered function of the
      sympathetic nervous system. In conclusion, spectral analysis of blood pressure
      variability for controlled test situations made it possible to detect differences
      in the cardiovascular regulatory systems between normotensive, borderline
      hypertensive, and mildly hypertensive individuals.

PMID- 8282327
TI  - Glucocorticoid increases angiotensin II type 1 receptor and its gene expression.
AB  - Recently, we demonstrated that glucocorticoid potentiates inositol triphosphate
      production evoked by angiotensin II in vascular smooth muscle cells. To clarify
      this mechanism, we investigated the effects of dexamethasone on the modulation of
      angiotensin II type 1 receptor and on postreceptor mechanisms in vascular smooth
      muscle cells. The number of angiotensin II type 1 receptors began to increase
      after 12 hours' incubation with dexamethasone. After 48 hours, the Bmax value
      reached 27 +/- 3 fmol/mg protein in dexamethasone-treated cells and 15 +/- 3
      fmol/mg protein in control cells. However, binding affinity did not change. A
      glucocorticoid antagonist, RU 38486, completely blocked these effects of
      dexamethasone. Also, to elucidate the effects of dexamethasone on postreceptor
      mechanisms, GTP analogue-induced inositol trisphosphate production in
      permeabilized cells was examined. Pretreatment with 1 mumol/L dexamethasone for
      48 hours did not affect these inositol trisphosphate productions. Moreover,
      dexamethasone had no effect on the level of Gq alpha protein. Furthermore, steady
      state levels of angiotensin II type 1 receptor messenger RNA were increased 2.2
      +/- 0.3-fold after 30 minutes' exposure to 1 mumol/L dexamethasone and 7.8 +/-
      0.4-fold after 24 hours. We conclude that glucocorticoid induced expression of
      the angiotensin II type 1 receptor gene and resulted in an increase in the number
      of angiotensin II type 1 receptors through the glucocorticoid-specific receptor,
      without significant effect on postreceptor systems in vascular smooth muscle
      cells.

PMID- 8282328
TI  - Are renal hemodynamics a key factor in the development and maintenance of
      arterial hypertension in humans?
AB  - The kidney plays a key role in the control of body fluids and blood pressure.
      Evidence has shown that impairment of renal function can lead to the development
      of arterial hypertension. The regulation of renal blood flow appears to be a key
      element in the pathophysiology of the hypertensive process, because multiple
      evidence suggests the existence of a functional enhancement of renal vascular
      tone in this disorder. The existence of renal vasoconstriction and of an
      inherited defect in the regulation of renal blood flow has been proposed in the
      prehypertensive stage. The mechanisms responsible for this alteration include a
      lack of modulation of the renal vasculature to angiotensin II, increased
      sympathetic activity, or suppressed renal dopaminergic activity. Established
      hypertension is characterized by elevated renal vascular resistance, decreased
      renal blood flow, sustained glomerular filtration rate, and increased filtration
      fraction. The increase in renal vascular resistance is initially due to
      elevations in renal vascular tone and is reversible, whereas later it becomes
      irreversible because of structural changes involved in nephrosclerosis.
      Antihypertensive drugs are able to decrease blood pressure and to prevent the
      development of further renal vascular damage independently of variable effects on
      renal hemodynamics.

PMID- 8282329
TI  - Platelet calcium transport in hypertension.
AB  - To determine platelet Ca2+ transport entities involved in increased cytosolic
      Ca2+ in the platelets of hypertensive individuals, we studied the relations
      between blood pressure and Ca2+ transporters in platelet membranes from 22 white
      male volunteers 32 to 68 years old. We used thapsigargin, a specific inhibitor of
      the internal membrane Ca(2+)-ATPase, to differentiate between plasma membrane and
      internal membrane Ca(2+)-ATPases. Inositol 1,4,5-trisphosphate-mediated and Ca2+
      ionophore (A23187)-induced Ca2+ release was also assayed in membrane preparations
      using rhod-2, a fluorescent Ca2+ indicator. Levels of glycoprotein IIIa, a
      possible component of agonist-mediated Ca2+ influx, were measured by
      immunoblotting. The results show that plasma membrane Ca(2+)-ATPase is decreased
      as a function of diastolic blood pressure (P < .002), whereas the internal
      membrane Ca(2+)-ATPase is not (P < .148). Neither activity is correlated with age
      or systolic blood pressure. However, inositol trisphosphate-mediated Ca2+ release
      is negatively correlated with age (P < .024) but not blood pressure. Glycoprotein
      IIIa levels and A23187-induced Ca2+ release were not related to age or blood
      pressure, demonstrating that inhibition of the plasma membrane Ca(2+)-ATPase was
      not a result of differences in the proportion of plasma membrane in the
      preparation or differences in intravesicular Ca2+ concentration. Inhibition of
      the plasma membrane Ca(2+)-ATPase could directly cause elevation of cytoplasmic
      Ca2+ and enhancement of platelet sensitivity.

PMID- 8282330
TI  - Responses to converting enzyme and renin inhibition. Role of angiotensin II in
      humans.
AB  - We compared the renal vascular responses to angiotensin converting enzyme
      inhibition and renin inhibition to assess the influence of angiotensin II (Ang
      II). We examined the renal and endocrine responses to the renin inhibitor
      enalkiren, to captopril, and to placebo in nine healthy and nine hypertensive men
      on a 10-mmol sodium diet. Ang II was infused to assess effects of the agents on
      renal and adrenal responsiveness to Ang II. Plasma Ang II concentration was
      suppressed similarly with enalkiren and captopril--an identical level of blockade
      was achieved. Although renal plasma flow was stable during placebo, a substantial
      rise was seen with both enalkiren (+133 +/- 26 mL/min per 1.73 m2) and captopril
      (+99.4 +/- 22.6). There was remarkable intrasubject concordance between the renal
      plasma flow responses to renin inhibition and converting enzyme inhibition (r =
      .90, P < .004). The vasodilator response to both agents correlated inversely with
      the fall in renal plasma flow induced by Ang II alone (r = -.66, P < .05). Both
      agents significantly enhanced the renal vascular response to Ang II (P = .01),
      and, furthermore, the renal vasodilator response to captopril predicted the
      potentiation of the renal plasma flow response to Ang II after either agent
      (enalkiren: r = .91, P < .001; captopril: r = .56, P < .05). Concordance of the
      maximal renal plasma flow response to the two agents appeared in the hypertensive
      men as well. Our results indicate that the acute renal response to captopril
      largely reflects a reduction in Ang II formation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8282331
TI  - Correlates of blood pressure in community-dwelling older adults. The
      Cardiovascular Health Study. Cardiovascular Health Study (CHS) Collaborative
      Research Group.
AB  - Although elevated blood pressure is an important predictor of cardiovascular
      disease and stroke in the elderly, little information exists on the distribution
      and risk factor correlates of blood pressure in this group. As part of the
      Cardiovascular Health Study, a population-based cohort study of 5201 men and
      women aged 65 to 101 years, we investigated correlates of systolic and diastolic
      blood pressure. Multiple regression analyses were conducted for all participants
      and a subgroup of 2482 without coronary heart disease and not on antihypertensive
      therapy (the "healthier" subgroup). In the total group, independent predictors of
      diastolic blood pressure included heart rate, aortic root dimension, creatinine,
      hematocrit, alcohol use, and black race (positive associations) and internal
      carotid artery wall thickness, mitral early/late peak flow velocity, white blood
      cell count, cigarette smoking, and age (negative associations). Positive
      predictors of systolic blood pressure included mitral late peak flow velocity,
      left ventricular mass, common carotid artery wall thickness, serum albumin,
      factor VII, diabetes, alcohol use, and age; negative predictors were coronary
      heart disease, uric acid, height, and smoking. In the healthier subgroup,
      positive predictors of diastolic blood pressure included heart rate, hematocrit,
      serum albumin, creatinine, and body weight, whereas mitral early/late peak flow
      velocity, serum potassium, smoking, and age inversely related to diastolic
      pressure. For the same group, common carotid artery wall thickness, left
      ventricular mass, serum albumin, factor VII, high-density lipoprotein
      cholesterol, and age were directly related to systolic blood pressure, whereas
      serum potassium was inversely related. Both systolic and diastolic pressures
      varied considerably by geographic site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282332
TI  - Antihypertensive effect of interleukin-2 in salt-sensitive Dahl rats.
AB  - We investigated the effects of interleukin-2, which stimulates the proliferation
      and maturation of thymus-derived lymphocytes, on hypertension and organ injuries
      in genetically hypertensive rats. Interleukin-2 (5 x 10(4) U/kg body wt) was
      subcutaneously injected into Dahl salt-sensitive rats fed a 4% NaCl diet and
      spontaneously hypertensive rats once a week for 10 weeks. The effects on blood
      pressure, cardiovascular hypertrophy, and renal function were evaluated.
      Interleukin-2 treatment lowered blood pressure in Dahl salt-sensitive rats (162
      versus 187 mm Hg, P < .005). This antihypertensive effect was associated with an
      increase in glomerular filtration rate (589 versus 428 mL/d per 100 g body
      weight, P < .005) and reduction in cardiac weight (268 versus 305 mg/100 g body
      weight, P < .05). Interleukin-2 also alleviated the marked glomerular sclerosis
      in Dahl salt-sensitive rats (glomerular injury score, 151 versus 220; P < .001).
      In contrast, interleukin-2 did not affect the development of hypertension or
      organ injuries in spontaneously hypertensive rats. Histologically, glomerular and
      arterial lesions of the kidney were much less marked in spontaneously
      hypertensive rats than in Dahl salt-sensitive rats. These data indicate that
      interleukin-2 ameliorates the development of hypertension and cardiac and renal
      injuries in Dahl salt-sensitive rats.

PMID- 8282333
TI  - Angiotensin converting enzyme inhibition prevents the increase in aortic collagen
      in rats.
AB  - Four groups of 4-week-old spontaneously hypertensive rats were treated during 4
      months with the angiotensin converting enzyme inhibitor quinapril at 1 mg/kg per
      day (Q1) or 10 mg/kg per day (Q10), hydralazine at 15 mg/kg per day (H), or
      placebo (P). In the first set of experiments, blood pressure was measured in
      conscious rats, and plasma and aortic angiotensin converting enzyme activities
      were evaluated. In the second set of experiments, histomorphometric parameters of
      the thoracic aorta were evaluated. Mean blood pressure was lower in the Q10 and H
      groups (136 +/- 16 and 149 +/- 11 mm Hg) compared with the P group (190 +/- 23 mm
      Hg) (P < .01). The Q1 group showed mean blood pressure values (171 +/- 15 mm Hg)
      lower than the P group (P < .05) but significantly higher than the Q10 and H
      groups (P < .01 and P < .05, respectively). Aortic medial cross-sectional area
      was significantly lower in the H and Q10 groups (455 +/- 61 and 487 +/- 57 x
      10(3) microns 2) than in the P group (636 +/- 72 x 10(3) microns 2) (P <
      .001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282334
TI  - Effects of a beta-blocker or a converting enzyme inhibitor on resistance arteries
      in essential hypertension.
AB  - Seventeen male untreated mild essential hypertensive patients aged 41 +/- 2 years
      agreed to participate in a double-blind randomized trial to test the effects of
      antihypertensive treatment on the structure and function of subcutaneous
      resistance arteries. Patients were treated with either 50 to 100 mg/d atenolol or
      2.5 to 5 mg/d cilazapril. Blood pressure before treatment was 148 +/- 6/99 +/- 1
      and 147 +/- 2/99 +/- 1 mm Hg, respectively. At 1 year of treatment blood pressure
      was 131 +/- 4/85 +/- 2 and 132 +/- 2/87 +/- 1 mm Hg, respectively. Resistance
      arteries (200 to 400 microns lumen diameter) dissected from subcutaneous gluteal
      biopsies obtained before treatment and at 1 year showed that the media-lumen
      ratio of arteries from patients treated with cilazapril was reduced to 6.31 +/-
      0.21% from 7.54 +/- 0.31% before treatment (P < .05), still slightly but
      significantly larger (P < .05) than the media-lumen ratio of resistance arteries
      of normotensive control subjects (5.15 +/- 0.30%). In contrast, in arteries from
      patients treated with atenolol there was no significant change with treatment
      (7.97 +/- 0.60% before and 8.07 +/- 0.45% after 1 year of treatment). Active wall
      tension responses to endothelin-1 were blunted in hypertensive patients and
      normalized in the cilazapril-treated patients. Depressed active media stress
      responses to norepinephrine, arginine vasopressin, and endothelin-1 were
      accordingly normalized in the patients receiving cilazapril as the media width
      became thinner but were unchanged in those taking atenolol.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8282335
TI  - Combined antihypertensive and lipid-lowering therapy in experimental
      glomerulonephritis.
AB  - We examined the interrelation between systemic hypertension, hyperlipidemia, and
      progressive renal injury in experimental glomerulonephritis. Induction of
      nephrotoxic serum nephritis in Sprague-Dawley rats led to systemic hypertension
      and hyperlipidemia. Four groups of rats were studied over a 16-week period: (1)
      untreated nephritic rats; (2) nephritic rats treated with hydralazine, reserpine,
      and lasix (AH); (3) nephritic rats treated with lovastatin (4 mg/kg) (Lova); and
      (4) nephritic rats treated with combined antihypertensive/lipid-lowering therapy
      (AH/Lova). Systolic blood pressure rose progressively in untreated rats (152 +/-
      4 mm Hg at 16 weeks). Blood pressure was reduced by antihypertensive therapy (P <
      .001) (108 +/- 2 mm Hg in the AH group and 111 +/- 3 mm Hg in the AH/Lova group)
      but remained elevated in animals treated with lovastatin alone (P > .05) (156 +/-
      3 mm Hg in the Lova group). Serum cholesterol rose progressively in untreated
      rats (3.70 +/- 0.85 mmol/L [143 +/- 33 mg/dL] at 16 weeks). The rise in serum
      cholesterol was prevented by lovastatin therapy (P < .001) (2.22 +/- 0.41 mmol/L
      [86 +/- 16 mg/dL] in the Lova group and 2.09 +/- 0.52 mmol/L [81 +/- 2 mg/dL] in
      the AH/Lova group) but not antihypertensive therapy (P > .05) (2.92 +/- 0.65
      mmol/L [113 +/- 25 mg/dL] in the AH group). Proteinuria was reduced by
      antihypertensive therapy (P < .001) and lipid-lowering therapy (P < .05) (16-week
      values: 1.069 +/- 0.167 g/d in untreated rats, 0.663 +/- 0.164 g/d in the Lova
      group, 0.392 +/- 0.051 g/d in the AH group, and 0.176 +/- 0.035 g/d in the
      AH/Lova group).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282336
TI  - Renal artery stenosis and ischemia. Effect on renal blood flow and extraction
      fraction.
AB  - The clearance of [131I]orthoiodohippurate and 99mTc-mercaptoacetyltriglycine
      provide a measure of effective renal plasma flow, yet these clearances are
      proportional to renal plasma flow only if the extraction fraction remains
      constant. To determine the effect of unilateral renal artery stenosis, captopril,
      renal ischemia, and partial renal vein occlusion on renal blood flow and the
      extraction fraction of [131I]orthoiodohippurate, 99mTc-mercaptoacetyltriglycine,
      and [125I]iothalamate, we conducted a series of constant infusion studies in
      Sprague-Dawley rats. Renal artery flow reduction of approximately 70% decreased
      the extraction fraction of all three agents (P < or = .05). Captopril had no
      effect on extraction fraction in controls, but it produced a further decrease in
      extraction fraction of 99mTc-mercaptoacetyltriglycine and
      [131I]orthoiodohippurate in rats with renal artery stenosis (P < or = .05).
      Ischemia resulted in a 16% decrease in flow (P < .01) but a much larger (47% to
      65%) decrease in extraction fraction of all three agents (P < .002). Partial
      renal vein occlusion also decreased the extraction fraction of all three agents
      (P < or = .05). The changes in extraction fraction imply that the clearances of
      [131I]orthoiodohippurate and 99mTc-mercaptoacetyltriglycine in disease states may
      not be proportional to renal plasma flow. Furthermore, in rats with renal artery
      stenosis it appears that renal blood flow must fall below a critical threshold of
      approximately 58% before extraction fraction decreases; as renal blood flow is
      further reduced below this threshold, there is a corresponding reduction in
      extraction fraction (P < .01).

PMID- 8282337
TI  - Proceedings of the 10th Scientific Meeting of the Inter-American Society of
      Hypertension. La Jolla, California, April 25-29, 1993.

PMID- 8282338
TI  - Insulin levels are similar in obese salt-sensitive and salt-resistant
      hypertensive subjects.
AB  - Evidence supports the hypothesis that hyperinsulinemia, especially in obesity,
      contributes to salt-sensitive hypertension by enhancing sodium retention and
      blunting the normal reduction of sympathetic drive and vascular resistance that
      occurs during a high versus low NaCl diet. To address these issues, we studied 18
      obese (body mass index, > 27 kg/m2) subjects younger than 45 years old with mild
      hypertension to determine if the salt-sensitive versus salt-resistant subset had
      higher insulin levels, retained more volume, and failed to suppress sympathetic
      drive and vascular tone normally on a high (approximately 200 mEq/d) versus low
      (20 mEq/d) NaCl diet for 7 days each. Six obese subjects were salt sensitive,
      with an 8.4 +/- 2.1 (SEM) mm Hg increase of ambulatory mean blood pressure on the
      high versus low NaCl diet. Ten obese subjects were salt resistant, with a 7.1 +/-
      0.9 mm Hg reduction of ambulatory mean blood pressure on high versus low NaCl.
      The salt-sensitive and salt-resistant groups had similar values, respectively,
      for the insulin area under the curve during an oral glucose tolerance test on low
      (14.6 +/- 1.8 versus 14.0 +/- 1.4 mU x min/dL, P = NS) and high (10.6 +/- 1.5
      versus 10.6 +/- 1.0, P = NS) salt diets. Although insulin levels were similar,
      insulin raised calf blood flow in salt-resistant subjects (P < .05) but not in
      salt-sensitive subjects on the high NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282339
TI  - Does plasma immunoreactive ouabain originate from the adrenal gland?
AB  - It was reported recently that the endogenous digitalis-like factor ouabain may
      mainly originate from the adrenal gland. To ascertain the pathophysiological
      significance of endogenous ouabain and to examine if it originates in the adrenal
      gland, we determined plasma immunoreactive ouabain levels in patients with
      various cardiovascular and endocrine diseases. Plasma immunoreactive ouabain
      levels were also determined in the adrenal venous blood by adrenal venous
      sampling. Plasma immunoreactive ouabain levels were significantly increased in
      patients with essential hypertension, primary aldosteronism, Cushing's syndrome,
      pheochromocytoma, acromegaly, and chronic renal failure. Plasma immunoreactive
      ouabain levels were decreased in patients with primary aldosteronism after
      unilateral adrenalectomy, acromegaly after pituitary adenomectomy, and chronic
      renal failure after hemodialysis. Plasma immunoreactive ouabain levels in
      patients after bilateral adrenalectomy were similar to those in healthy subjects.
      There was no significant step-up of immunoreactive ouabain levels in the adrenal
      vein from the peripheral vein in three patients, whereas one patient with
      hypertension and right adrenal tumor but without any known adrenal hormone excess
      showed higher plasma immunoreactive ouabain levels in the right adrenal vein than
      those in the peripheral vein. These results suggest an important
      pathophysiological significance of endogenous ouabain in various cardiovascular
      and endocrine diseases. It is unlikely that the adrenal gland is a major source
      of plasma ouabain, although a possible excess production of ouabain by the
      adrenal tumor remains to be elucidated.

PMID- 8282340
TI  - Chronic blood pressure effects of bufalin, a sodium-potassium ATPase inhibitor,
      in rats.
AB  - Endogenous Na+,K(+)-ATPase inhibitors may have a role in the mechanism of low
      renin hypertension. Two such compounds have been characterized: ouabain from
      human plasma and resibufogenin from toad plasma. Previously, we examined the
      acute effects of ouabain and bufalin (which has the same structure as
      resibufogenin except for one H+) in normal rats. Bufalin raised blood pressure,
      but ouabain had little effect. In contrast, given chronically, ouabain
      substantially increased blood pressure in normal rats and 70% reduced renal mass
      rats on a salt-free diet. We have now examined the chronic effects of bufalin in
      rats. Normal rats received 14.8 micrograms/kg per day bufalin or an equimolar
      dose of ouabain intraperitoneally for 6 weeks; 70% reduced renal mass rats also
      received 14.8 micrograms/kg per day bufalin. Another group of normal rats
      received 29.6 micrograms/kg per day bufalin intraperitoneally for 6 weeks.
      Respective control animals received vehicle. In contrast to ouabain, blood
      pressure did not increase in normal rats receiving the 14.8 micrograms dose of
      bufalin. However, normal rats receiving 29.6 micrograms bufalin and 70% reduced
      renal mass rats receiving 14.8 micrograms bufalin developed significant increases
      in blood pressure. Increases in blood pressure were associated with decreases in
      myocardial Na+,K(+)-ATPase activity and correlated with increased plasma Na+,K(+)
      ATPase inhibitory activity. Thus, although bufalin is a more potent pressor agent
      than ouabain when both agents are given acutely, ouabain is at least as potent a
      vasopressor agent as bufalin when given chronically. Thus, both are pressor
      agents, more so in the presence of reduced renal mass, when given chronically in
      the rat.

PMID- 8282341
TI  - Participation of ouabainlike compound in reduced renal mass-saline hypertension.
AB  - We examined the role of ouabainlike compound in reduced renal mass-saline
      hypertension using a population of rats immunized with ouabain. To develop
      ouabain-immunized rats, ouabain-bovine serum albumin conjugates were injected
      subcutaneously three times at 4-week intervals. Titer determinations were made 2
      weeks after the third immunization, and rats with high titers were used in the
      study. Immunoglobulin G fractions from ouabain-immunized rats effectively
      inhibited the contractile response of guinea pig aorta to exogenous ouabain (150
      nmol). Fourteen ouabain-immunized and seven nonimmunized control rats underwent
      subtotal nephrectomy. An additional eight ouabain-immunized and six nonimmunized
      rats served as sham-operated rats. Four groups of rats drank 1% NaCl solution for
      3 weeks, and systolic blood pressure was measured weekly by the tail-cuff method.
      Two groups of sham-operated rats remained normotensive. In contrast, two groups
      of subtotally nephrectomized rats developed hypertension. However, among these
      rats, systolic blood pressure was significantly lower in ouabain-immunized rats
      than in nonimmunized rats (161 +/- 5 versus 180 +/- 3 [+/- SEM) mm Hg, P < .01).
      The decrease in blood pressure was accompanied by a significant inhibition of
      aortic hypertrophy (P < .05). These results indicate that chronic blockade of
      circulating ouabainlike compound partly ameliorates reduced renal mass-saline
      hypertension and suggest that circulating ouabainlike compound may be involved in
      the pathophysiology in this model of hypertension.

PMID- 8282342
TI  - Renal arteriolar angiotensin responses during varied adenosine receptor
      activation.
AB  - We performed experiments to test the hypothesis that endogenous adenosine acts as
      an essential cofactor required for eliciting angiotensin II (Ang II)-induced
      afferent and/or efferent arteriolar vasoconstriction. Enalaprilat (2 mg IV) was
      administered to anesthetized rats to reduce endogenous Ang II levels. Kidneys and
      blood were harvested from these animals and used for study of renal microvascular
      function using the in vitro blood-perfused juxtamedullary nephron technique.
      Arteriolar inside diameter was monitored videomicroscopically in (1) normal
      kidneys, (2) kidneys subjected to adenosine receptor blockade (100 mumol/L 1,3
      dipropyl-8-p-sulfophenylxanthine), and (3) kidneys continuously exposed to 1
      mumol/L adenosine. Under resting conditions, arteriolar diameters were similar in
      all three groups of kidneys, averaging 24.8 +/- 1.0 microns (n = 23) in afferent
      arterioles and 24.0 +/- 0.9 microns (n = 16) in efferent arterioles. In normal
      kidneys, adenosine (10 mumol/L) decreased both afferent (10.2 +/- 2.0%) and
      efferent (6.5 +/- 0.8%) diameters, an effect that was absent in kidneys subjected
      to adenosine receptor blockade. Ang II (10 pmol/L to 100 nmol/L) elicited dose
      dependent vasoconstriction of both vascular segments in normal kidneys. At a
      concentration of 100 nmol/L, Ang II decreased afferent diameter by 36.8 +/- 8.5%
      and efferent diameter by 30.8 +/- 9.6%. Neither afferent nor efferent arteriolar
      Ang II dose-response relations were significantly different in kidneys treated
      with low-dose adenosine or the adenosine receptor blocker. These observations
      refute the hypothesis that a receptor-mediated action of adenosine is required
      for Ang II-induced constriction of juxtamedullary afferent or efferent
      arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282343
TI  - Hyperinsulinemia in normotensive offspring of hypertensive parents.
AB  - Hyperinsulinemia and insulin resistance have been extensively reported in adult
      patients with essential hypertension. The aim of this study was to examine serum
      glucose and insulin levels both in the fasting state and after 0.25 g/kg IV
      glucose and to relate those findings to the status of intracellular Na+ and red
      blood cell Na(+)-Li+ countertransport in a population of 21 normolipemic
      normotensive offspring of hypertensive parents (N-EH) and 13 control children
      without a history of parental essential hypertension or diabetes mellitus matched
      for age, body mass index, and pubertal stage. Offspring of hypertensive parents
      presented significantly higher serum insulin levels both after an overnight fast
      (17.4 +/- 1.6 versus 11.6 +/- 1.6 microU/mL in control [mean +/- SEM], P < .01)
      and after intravenous glucose than control subjects (insulin area under the
      curve, 3015 +/- 310 and 2057 +/- 234 microU/mL per hour, respectively, P < .01).
      No relation could be established between the high red blood cell Na(+)-Li+
      countertransport (343 +/- 22 versus 215 +/- 15 mumol/L per hour, N-EH versus
      control; P < .002) or high intracellular Na+ (9.8 +/- 0.28 versus 8.7 +/- 0.36
      mEq/L, N-EH versus control) and hyperinsulinemia found in children of
      hypertensive parents. We conclude that the time precedence of hyperinsulinemia
      (and possibly insulin resistance) over the appearance of clinical hypertension in
      a high-risk population further supports the contention that an abnormal insulin
      action may play a pathogenetic role in essential hypertension.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8282344
TI  - Mechanism by which angiotensin II stabilizes messenger RNA for angiotensinogen.
AB  - The most important specific regulatory mechanism for hepatic angiotensinogen
      synthesis and secretion is its stimulation by angiotensin II, the effector
      peptide of the renin-angiotensin system. In the circulating system, this
      octapeptide is thought to stimulate hepatic angiotensinogen synthesis through a
      positive feedback loop. In the present study, we have identified the
      intracellular mechanisms leading to an increase in angiotensinogen messenger RNA
      (mRNA) and secretion. In a [3H]uridine-dependent pulse and chase system as well
      as in hepatocytes in which de novo synthesis of mRNA has been blocked by
      actinomycin D or 5,6-dichlorobenzimidazole riboside, angiotensin II significantly
      increased the half-life of angiotensinogen mRNA. In contrast, no effect of
      angiotensin II on the transcription of angiotensinogen mRNA could be observed in
      a nuclear run-on assay with nuclei from pretreated hepatocytes, whereas
      dexamethasone, as a positive control, increased the transcription fivefold to
      sevenfold. We have isolated a 12-kD protein from the polysomal fraction of
      isolated hepatocytes, which has an affinity to the nontranslated 3' tail of
      angiotensinogen mRNA. For in vitro transcription of this mRNA fragment, the DNA
      sequence coding for the nontranslated 3' tail was excised from the vector pRAG 16
      and cloned into the transcription vector pGEM 5zf+. Molecular weight and
      isoelectric point of the mRNA-binding protein correspond to the parameters of a
      cytosolic protein that becomes phosphorylated by decreased cyclic AMP
      concentrations as analyzed in [32P]orthophosphate-loaded hepatocytes. In a
      cytosolic incubation system in which the polysomal fraction was integrated, the
      mRNA-binding protein increased the half-life of angiotensinogen mRNA
      significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282345
TI  - Role of the lipoxygenase pathway in angiotensin II-induced vascular smooth muscle
      cell hypertrophy.
AB  - The 12-lipoxygenase pathway is a key mediator of angiotensin II (Ang II)-induced
      effects in the adrenal cortex. We also recently demonstrated that Ang II
      increases 12- and 15-lipoxygenase product levels in vascular smooth muscle cells.
      However, the relation between lipoxygenase activation and Ang II-induced vascular
      smooth muscle cell hypertrophy is not known. We studied the effects of Ang II and
      12-lipoxygenase products on both total cell protein content and the levels of the
      matrix protein fibronectin in quiescent porcine aortic smooth muscle cells. Ang
      II-induced increases in cellular protein content were attenuated by the specific
      12-lipoxygenase inhibitor baicalein; in contrast, the cyclooxygenase inhibitor
      ibuprofen had no effect. Direct addition of the 12-lipoxygenase product 12-S
      hydroxyeicosatetraenoic acid increased total cell protein content. We have
      recently shown that porcine vascular smooth muscle cell growth is potentiated in
      high glucose (25 mmol/L) culture conditions. We observed that both Ang II and 12
      S-hydroxyeicosatetraenoic acid induced a greater increase in protein content in
      cells cultured for two passages in high glucose. Furthermore, Ang II and 12-S
      hydroxyeicosatetraenoic acid also markedly increased fibronectin levels in cells
      cultured in high glucose. These results suggest that 12-lipoxygenase activation
      plays a key role in Ang II-induced vascular smooth muscle cell hypertrophy.
      Furthermore, both Ang II and lipoxygenase effects are enhanced in cells cultured
      under hyperglycemic conditions.

PMID- 8282346
TI  - Stimulation of vascular glycosaminoglycan synthesis by subpressor angiotensin II
      in rats.
AB  - The vascular trophic effects of angiotensin II (Ang II) in small doses may
      precede its hypertension-producing effect, and de novo synthesis of components of
      extracellular matrix may be a requirement for Ang II-stimulated growth. In the
      present study, therefore, the incorporation of 35SO4 into glycosaminoglycans
      (synthesis) of aorta and bladder wall of young adult, male Sprague-Dawley rats
      was measured ex vivo after 48 hours of Ang II administration at two dose levels,
      100 and 200 ng.kg-1.min-1 IP. Vehicle-infused rats served as controls. Compared
      with controls, systolic blood pressure was unchanged in rats receiving 100 ng.kg
      1.min-1 Ang II and rose by 13 mm Hg (P < .05) in rats receiving the 200-ng.kg
      1.min-1 dose. In Ang II-treated rats, glycosaminoglycan synthesis of the aorta
      was increased by 20% (P < .05) and 52% (P < .005) at the two dose levels,
      respectively. Glycosaminoglycan synthesis of bladder smooth muscle was also
      increased in Ang II-treated rats (P < .01), but the response was not dose
      dependent. By 7 to 10 days of Ang II administration (200 ng.kg-1.min-1),
      glycosaminoglycan synthesis of aorta returned toward baseline (P < .10, > .05).
      The rate of synthesis of subtypes of glycosaminoglycans in the aorta was
      proportionately increased by Ang II. The early occurrence, magnitude, and
      arterial pressure independence of Ang II-induced glycosaminoglycan synthesis
      suggest that restructuring of extracellular matrix may play an important role in
      both the trophic and hypertension-producing action of Ang II.

PMID- 8282347
TI  - Consistency of ethnic differences in children's pressor reactivity. 1987 to 1992.
AB  - In this prospective investigation, all children enrolled in the public third
      grade classrooms of an entire county (n = 474) had blood pressure measured both
      at rest and during a stressful television video game. Examinations were repeated
      in 4 subsequent years when cohort children as well as newly enrolled children
      were in grades 4, 5, 7, and 8. Both cross-sectional and longitudinal analyses
      indicated that black children demonstrated significantly greater systolic and
      diastolic pressor reactivity than white children. These data suggest that ethnic
      differences in children's pressor reactivity presage ethnic differences in
      adulthood hypertension.

PMID- 8282348
TI  - Effects of sarcoplasmic reticulum calcium pump inhibitors on vascular smooth
      muscle.
AB  - A dysfunctioning of Ca2+ pump ATPase in the sarcoplasmic reticulum in vascular
      smooth muscle has been proposed as a contributing factor for the development of
      genetic hypertension. In this study, we determined whether in vitro inhibition of
      the sarcoplasmic reticulum Ca2+ pump in vascular smooth muscle tissues and
      cultured cells isolated from aortas of spontaneously hypertensive rats (SHR) and
      Wistar-Kyoto (WKY) rats would elicit the known alterations of contractile
      function and cell growth. We found the following common vascular effects of
      thapsigargin and cyclopiazonic acid, which are known to be selective inhibitors
      of sarcoplasmic reticulum Ca(2+)-ATPase in a number of tissues including smooth
      muscle: (1) Both sarcoplasmic reticulum Ca2+ pump inhibitors diminished agonist
      induced transient contraction in Ca(2+)-free medium (ie, contraction due to
      intracellular release of Ca2+) and enhanced nifedipine-sensitive contraction on
      readmission of Ca2+ (ie, Ca2+ influx via L-type channels); and (2) thapsigargin
      and cyclopiazonic acid inhibited the attachment of cultured aortic muscle cells
      to the substrate in a similar degree in both SHR and WKY cells, but SHR cells
      were more sensitive than WKY cells to the inhibition of cell proliferation by
      these two agents. The first effect may provide an explanation for several
      contractile abnormalities known to be associated with elevated cytosolic Ca2+
      concentration, whereas the second effect suggests that elevation of cytosolic
      Ca2+ in aortic smooth muscle cells is not necessarily associated with or
      sufficient to account for the accelerated cellular proliferation in SHR. These
      results, however, further stress the functional importance of impairment of Ca2+
      regulation in vascular smooth muscle cells in genetic hypertension.

PMID- 8282349
TI  - Chronic hyperinsulinemia augments deoxycorticosterone acetate-salt hypertension.
AB  - To evaluate the effect of chronic hyperinsulinemia on blood pressure in salt
      dependent hypertension, we infused insulin (1.0 IU/d, n = 15) or saline (n = 13)
      for 4 weeks into deoxycorticosterone acetate-salt hypertensive rats. The insulin
      infusion increased plasma insulin levels to 24 +/- 2 microU/mL, which was higher
      than in the saline-infused rats (9 +/- 1 microU/mL) but was still within the
      physiological range. Blood pressure was measured by the tail-cuff method twice a
      week, and daily sodium intake and urinary sodium excretion were calculated for 3
      weeks. At week 4, arterial pressor responsiveness to norepinephrine, angiotensin
      II, and hexamethonium bromide was evaluated. After 14 days of chronic infusion,
      the insulin group showed a higher blood pressure than the saline group (on 21st
      day: 178 +/- 6 versus 156 +/- 5 mm Hg, P < .05 by tail-cuff method; 171 +/- 4
      versus 149 +/- 3 mm Hg, P < .05 by direct intra-arterial measurement). This blood
      pressure difference was eliminated after ganglionic blockade with hexamethonium
      bromide (86 +/- 4 mm Hg in insulin-treated and 89 +/- 4 mm Hg in saline-treated
      rats by direct intra-arterial measurement). Throughout the experiment, neither
      sodium balance nor arterial pressor responsiveness to norepinephrine or
      angiotensin II differed between the two groups. In conclusion, chronic
      hyperinsulinemia in the physiological range augments the development of
      hypertension in salt-dependent hypertension, and this augmentation may be
      mediated by sympathetic stimulation independent of salt retention.

PMID- 8282350
TI  - Effect of lisinopril and metoprolol on arterial distensibility.
AB  - Apart from lowering blood pressure, antihypertensive drugs may influence vessel
      wall function. In a randomized double-blind study, the effect of lisinopril and
      metoprolol on arterial distensibility was studied in 40 patients with essential
      hypertension. After a placebo run-in period, the patients were randomly treated
      with metoprolol (50, 100, or 200 mg) or lisinopril (5, 10, or 20 mg) for 10
      weeks. In the lisinopril group, blood pressure decreased after 10 weeks of
      therapy from 173 +/- 10/102 +/- 5 to 155 +/- 10/85 +/- 3 mm Hg and in the
      metoprolol group from 167 +/- 12/102 +/- 4 to 153 +/- 8/84 +/- 3 mm Hg. Diameter
      (millimeters), relative change in diameter (percent), and distensibility (10(
      3)/kPa) of the left common carotid artery were determined after the placebo run
      in period and after 6 and 10 weeks of antihypertensive therapy. A multigate
      Doppler system was used to measure the vessel wall movements by Doppler analysis
      in M-mode; blood pressure was recorded by finger plethysmography (Finapres).
      Neither lisinopril nor metoprolol influenced the end-diastolic diameter of the
      common carotid artery after 6 and 10 weeks of treatment. In the lisinopril group,
      a significant increase of percent change in diameter (P < .05 compared with the
      baseline value; P < .05 compared with the metoprolol group) and distensibility (P
      < .01 compared with the baseline value; P < .05 compared with the metoprolol
      group) was observed. The results show that lisinopril but not metoprolol improves
      arterial distensibility in essential hypertension. Pressure-independent effects
      of angiotensin converting enzyme inhibitors may be important modulators of
      adaptive changes in the arterial wall.

PMID- 8282351
TI  - Myocardial scintigraphic characteristics in patients with primary aldosteronism.
AB  - To evaluate the difference in myocardial damage between primary aldosteronism and
      untreated essential hypertension, we performed thallium-201 myocardial single
      photon emission computed tomography in 10 patients with primary aldosteronism and
      10 patients with essential hypertension who were matched for age, sex, blood
      pressure, and the severity of left ventricular hypertrophy for primary
      aldosteronism. From the analysis of thallium-201 myocardial scintigraphy, extent
      score was calculated. Extent score was significantly higher in primary
      aldosteronism than in essential hypertension (45.8 +/- 23.5% versus 9.5 +/- 7.3%,
      P < .01). After operation, blood pressure significantly decreased, and the
      precordial voltages (SV1 + RV5) and left ventricular mass indexes were
      significantly reduced in patients with primary aldosteronism. Extent score was
      also significantly improved. These results suggest that despite the same severity
      of myocardial hypertrophy between primary aldosteronism and essential
      hypertension, the myocardial damage estimated by thallium-201 myocardial
      scintigraphy is more severe in primary aldosteronism than in essential
      hypertension. Extent score was useful for evaluation of the severity of
      myocardial damage in hypertensive patients.

PMID- 8282352
TI  - Left ventricular mass and cardiovascular reactivity in young men.
AB  - The relation between left ventricular wall thickness and mass, arterial plasma
      catecholamines, and blood pressure at rest and during a mental arithmetic
      challenge and a cold pressor test was examined in 69 healthy men 19 years of age.
      The subjects were recruited from the 1st (n = 21), 50th (n = 26), and 99th (n =
      22) percentiles in mean blood pressure. All underwent echocardiography to
      determine mean wall thickness and left ventricular mass. Continuous intra
      arterial blood pressure, electrocardiogram, and arterial sampling of plasma
      catecholamines were performed after 30 minutes of supine rest, during a 5-minute
      mental arithmetic challenge, and during a 1-minute cold pressor test. Stepwise
      multiple-regression analyses considering mean wall thickness and left ventricular
      mass as the dependent variables were applied. Intra-arterial systolic blood
      pressure (r = .54, P < .0001) and arterial plasma epinephrine (r = .31, P = .009)
      after 30 minutes of supine rest were the only independent explanatory variables
      of mean wall thickness (multiple R2 = .33, P < .0001). Blood pressure at
      screening and during mental stress and cold pressor tests were not independent
      explanatory variables. The present study suggests that resting arterial blood
      pressure and plasma epinephrine may be of importance for development of left
      ventricular hypertrophy.

PMID- 8282353
TI  - Three-dimensional echocardiography. Advances for measurement of ventricular
      volume and mass.
AB  - There is a need for more accurate and reproducible serial measurement of left
      ventricular volume and mass in individual subjects by echocardiography.
      Conventional echocardiography has significant measurement variability because of
      its use of geometric assumptions and image plane positioning errors. Guided three
      dimensional echocardiography eliminates geometric assumptions and reduces image
      plane positioning errors by using a "line of intersection" display. Use of three
      dimensional guided imaging for a one-dimensional measurement of the left
      ventricle resulted in a threefold improvement of interobserver variability over
      conventional echocardiographic measurements. Computer-aided three-dimensional
      reconstruction of the ventricle for ventricular volume from a series of 8 to 10
      short-axis images also achieved more than a threefold improvement of
      interobserver variability compared with two-dimensional echocardiography. Three
      dimensional echocardiographic computation of ventricular volume and mass in
      healthy subjects was achieved with an accuracy comparable to magnetic resonance
      imaging and was superior to two-dimensional echocardiography. Three-dimensional
      echocardiography promises to be a more accurate method of estimating left
      ventricular volume and mass and may be suitable for serial study of individual
      subjects because of its improved accuracy and decreased interobserver variability
      compared with conventional echocardiographic methods.

PMID- 8282354
TI  - Effects of chlorthalidone on ventricular hypertrophy in deoxycorticosterone
      acetate-salt hypertensive rats.
AB  - Diuretics have been the mainstay of long-term treatment of hypertension, but
      there is no evidence suggesting that diuretics may be effective in reducing
      cardiac hypertrophy associated with hypertension. Thus, the present study was
      carried out to elucidate if long-term treatment with chlorthalidone (8 mg per
      animal per day added to food) affects the development of and reverses the
      ventricular hypertrophy in deoxycorticosterone acetate (DOCA) (8 mg/kg SC twice a
      week)-salt hypertensive rats. Chlorthalidone was given to one group during all 20
      days of DOCA administration (preventive regimen) and to another group 20 days
      after DOCA treatment was initiated until the 40th day (therapeutic regimen).
      Chlorthalidone was found to reduce or prevent the development of ventricular
      hypertrophy, as assessed by a reduction in ventricular mass and cardiac protein
      as well as arterial hypertension. Both chlorthalidone regimens prevented the
      increase or induced a significant decrease in the plasma concentration of sodium
      and in cardiac sympathetic tone, which were both increased in DOCA-salt-treated
      rats. These data provide evidence that long-term chlorthalidone treatment is
      effective in preventing or reducing ventricular hypertrophy along with arterial
      hypertension. However, whether this is due to a reduction in plasma sodium or
      other additional mechanisms, such as a reduction in cardiac sympathetic tone,
      remains to be determined.

PMID- 8282355
TI  - Vascular kallikrein in deoxycorticosterone acetate-salt hypertensive rats.
AB  - We determined the status of vascular kallikrein in rats with severe hypertension
      caused by treatment with deoxycorticosterone acetate (DOCA) and drinking of 1%
      NaCl for 6 weeks. We assayed active and total kininogenase (kallikrein) activity
      in the perfusate and in arterial and venous tissue. DOCA-salt rats had higher
      systolic blood pressure at 6 weeks (214 +/- 5 mm Hg) than rats drinking tap water
      (135 +/- 4 mm Hg) or saline (145 +/- 8 mm Hg). Kininogenase in the perfusate
      (nanograms bradykinin per minute per kilogram body weight) increased
      significantly at 2 weeks, from 5.8 +/- 2.1 to 8.9 +/- 1.4 for active kallikrein
      and from 28.7 +/- 0.4 to 48.7 +/- 2.9 for total kallikrein. Total kallikrein
      returned to control values at 4 weeks, whereas it was significantly reduced at 6
      weeks (20.9 +/- 0.7). Active kallikrein was significantly depressed at 4 and 6
      weeks (1.08 +/- 0.1 and 0.85 +/- 0.1, respectively [P < .05]). Active kallikrein
      in arterial tissue (picograms bradykinin per milligram per minute) showed a small
      but significant increase at 2 weeks, from 156 +/- 7 to 201 +/- 10 (P < .05),
      finally decreasing significantly by 6 weeks to 64 +/- 3; however, total
      kallikrein showed a significant decrease only at 6 weeks, from 844 +/- 17 to 427
      +/- 27. Both active and total kallikrein in the veins were higher than control
      values at 2 weeks, changing from 437 +/- 7 to 541 +/- 19 and from 1619 +/- 17 to
      2062 +/- 86, respectively. Venous kallikrein remained elevated until the end of
      the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282356
TI  - Cardiovascular effects of brain kinin receptor blockade in spontaneously
      hypertensive rats.
AB  - We studied the role of brain kinins in the regulation of cardiovascular function.
      Intracerebroventricular injection of 380 pmol bradykinin increased mean blood
      pressure by 20 +/- 2 mm Hg (P < .01) in normotensive Wistar-Kyoto (WKY) rats.
      Complete inhibition of this effect was achieved with intracerebroventricular
      administration of the newly synthesized, long-acting B2 receptor antagonist D
      Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140). On a molar basis, Hoe 140 was
      two orders of magnitude more potent than antagonists of the first generation.
      Baroreceptor sensitivity, estimated as the heart rate response to blood pressure
      changes induced by intravenous injection of phenylephrine or sodium
      nitroprusside, was not altered by Hoe 140 in WKY rats. In spontaneously
      hypertensive rats (SHR), baroreceptor reflex sensitivity to increments in mean
      blood pressure was reduced by Hoe 140 (mean slope value: -0.47 +/- 0.07 versus 
      0.92 +/- 0.13 beats per minute per millimeter of mercury in controls, P < .05).
      Hoe 140 did not affect the tachycardic component of the baroreceptor reflex. Two
      week intracerebroventricular infusion of Hoe 140 did not alter systolic blood
      pressure or heart rate in WKY rats. In SHR, systolic blood pressure increased (P
      < .01) similarly during the infusion of Hoe 140 or vehicle (from 174 +/- 6 to 220
      +/- 5 mm Hg and 178 +/- 4 to 210 +/- 4 mm Hg at 2 weeks, respectively), whereas
      heart rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282357
TI  - Biochemical evidence of a kallikrein-like activity in rat reproductive tissues.
AB  - We performed this study to examine the presence of a kallikrein-kinin system in
      rat fetal and maternal tissues. Uteri and placenta from Wistar pregnant and
      nonpregnant rats were perfused to eliminate blood, and fetal membranes were
      washed several times with saline. Amniotic fluids were obtained without blood
      contamination by amniocentesis from eight rats. The different samples were
      homogenized and centrifuged (2000g during 20 minutes), and the supernatant was
      incubated with dog kininogen and 0.1 mol/L Tris-HCl buffer (pH 8.5) in the
      presence of peptidase inhibitors. Kinins released were measured by
      radioimmunoassay. Kininogenase activity was found in rat uteri, placental
      vessels, amniotic fluids, and fetal membranes. The enzymes were present in active
      but mostly in inactive forms. The kallikrein-like enzymes found in the different
      preparations and rat urinary kallikrein used as control had similar molecular
      weights, immunologic characteristics, and inhibition profiles with protease
      inhibitors. We conclude that kallikrein-like enzymes are present in rat organs of
      reproduction. These data suggest that kinins released locally may act as
      paracrine hormones in the regulation of blood pressure during pregnancy.

PMID- 8282358
TI  - Increased cytosolic sodium and reduced Na,K-ATPase activity in transgenic rats.
AB  - The transgenic rat TGR(mRen2)27 is a new monogenetic model in hypertension
      research that develops fulminant hypertension after the mouse Ren-2d renin gene
      has been integrated into its genome. To evaluate the molecular mechanism of
      development of hypertension in this animal model, we measured cytosolic free
      sodium concentration in intact lymphocytes from seven transgenic rats and eight
      age-matched normotensive Sprague-Dawley rats using the novel sodium-sensitive
      fluorescent dye sodium-binding benzofuranisophthalate. Resting cytosolic sodium
      was significantly higher in transgenic rats compared with Sprague-Dawley rats
      (31.7 +/- 2.2 versus 18.2 +/- 0.4 mmol/L, mean +/- SEM, P < .001). Inhibition of
      Na,K-ATPase by 0.5 mmol/L ouabain for 5 minutes significantly increased
      lymphocytic cytosolic sodium in Sprague-Dawley rats to 36.5 +/- 3.4 mmol/L (P <
      .001 compared with resting value), whereas no significant change could be
      observed in transgenic rats (35.4 +/- 0.6 mmol/L), indicating that Na,K-ATPase is
      less responsive in transgenic rats. The Na,K-ATPase activity from erythrocytes
      was measured with an enzyme-linked assay. Na,K-ATPase activity was significantly
      reduced in transgenic rats compared with Sprague-Dawley rats (4.0 +/- 0.3 versus
      8.1 +/- 0.6 U/L, P < .001). We concluded that reduced Na,K-ATPase activity leads
      to elevated cytosolic sodium in this model of genetic hypertension.

PMID- 8282359
TI  - Salt-regulating hormones in young normotensive obese subjects. Effects of saline
      load.
AB  - To investigate whether the response of salt-regulating hormones to volume
      expansion is impaired in obese subjects, we assessed the effects of saline load
      (0.25 mL/kg.min.120 min) in 9 young, healthy, normotensive obese subjects (body
      mass index, > 30 kg/m2) and in 10 lean control subjects (body mass index, < 25
      kg/m2) matched for age, gender, height, and mean blood pressure. Hematocrit,
      plasma renin activity (PRA), plasma aldosterone (PA), atrial natriuretic factor
      (ANF), and urinary sodium excretion (UNaV) were evaluated. Saline load increased
      ANF levels significantly (P < .001) in lean subjects at both 60 and 120 minutes,
      whereas they decreased in obese subjects. Such decreases became significant (P <
      .01) at 120 minutes. Suppression of PRA and PA by saline load were more marked in
      lean than obese subjects. Hematocrit decreased in both groups, and UNaV increased
      more in lean than obese subjects during saline load. Comparisons of percent
      changes in ANF, PRA, and PA after saline load showed that the responses of lean
      and obese subjects were significantly different (P < .001 for ANF at both 60 and
      120 minutes; P < .05 for PRA and PA at both 60 and 120 minutes). In conclusion,
      the lack of ANF response and the reduced suppression of PRA and PA to saline load
      indicate a dysfunction of these systems in obese subjects. This alteration may be
      involved in the higher susceptibility of obese subjects to developing
      hypertension.

PMID- 8282360
TI  - Combined versus single effect of fosinopril and hydrochlorothiazide in
      hypertensive patients.
AB  - The antihypertensive effect and safety of fosinopril and hydrochlorothiazide
      combined were compared with each drug singly and placebo in a controlled manner.
      After a 4- to 5-week placebo lead-in period, 67 mild to moderate essential
      hypertensive patients (seated diastolic blood pressure > or = 95 and < or = 110
      mm Hg) were randomized in a double-blind fashion into four parallel treatment
      groups: 20 mg fosinopril plus 12.5 mg hydrochlorothiazide, 20 mg fosinopril, 12.5
      mg hydrochlorothiazide, and placebo during 8 weeks. Patients were seen biweekly.
      Sitting diastolic blood pressure was the outcome variable defining therapeutic
      response. The efficacy of fosinopril plus hydrochlorothiazide as a combined
      therapy was superior to any single drug (P < .05) and placebo (P < .01) in the
      treatment of mild to moderate essential hypertension. Mean adjusted
      systolic/diastolic blood pressure decrements at week 8 were -18.8/-13.7, -12.9/
      11.8, -8.5/-9.3, and -2.7/-6.9 mm Hg for the fosinopril plus hydrochlorothiazide,
      fosinopril, hydrochlorothiazide, and placebo groups, respectively. Clinical
      adverse events and laboratory changes documented throughout the study were
      similar to placebo and were mild in severity in all groups.

PMID- 8282361
TI  - Timing for administration of an antihypertensive drug in the treatment of
      essential hypertension.
AB  - To find the best timing for administration of long-acting antihypertensive drugs,
      we gave nitrendipine, a calcium antagonist of the dihydropyridine group, once a
      day to six hospitalized and drug-free patients with essential hypertension,
      changing the time of administration and studying the effects on the circadian
      rhythm of blood pressure. After control values of 24-hour blood pressure
      variations were taken with patients on placebo, a 10-mg tablet of nitrendipine
      was given for 3 days on three occasions--at 6 AM on awakening, at 8:30 AM after
      breakfast, and at 6 PM after supper; 24-hour blood pressure values for each
      period were recorded on the third day. The 24-hour blood pressure values during
      the control period showed a biphasic circadian rhythm, with higher values during
      wakefulness and lower values during sleep. The control period was also
      characterized by a rapid rise in blood pressure on awakening, the so-called
      morning surge of blood pressure, and a gradual decline during sleep at night.
      Although the morning surge was not completely suppressed by nitrendipine given
      after breakfast, it was diminished by the drug given on awakening or after
      supper; the latter brought a deeper decline in blood pressure during sleep
      compared with other times. The average of 24-hour blood pressure values obtained
      by nitrendipine given on awakening was the lowest among the three occasions.
      Thus, administration of long-acting calcium antagonists with a rapid onset of
      action on awakening in the early morning seems to be a more rational and
      beneficial alternative than the conventional administration after
      breakfast.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282362
TI  - Felodipine therapy may not alter glucose and lipid metabolism in hypertensives.
      Felodipine Multicenter Prospective Study Group in Japan.
AB  - The effects of long-term monotherapy with felodipine, a calcium antagonist, on
      blood pressure, glucose tolerance, and serum lipid profiles were prospectively
      investigated in 51 hypertensive patients: 13 with normal glucose tolerance and 38
      with glucose intolerance. The levels of plasma glucose, serum lipids, and
      glycosylated hemoglobin A1c were determined before and during long-term (7.5 +/-
      0.5 months; range, 6 to 9 months) therapy with felodipine. A 75-g oral glucose
      tolerance test was performed before and during long-term felodipine therapy.
      Significant decreases in both systolic and diastolic blood pressures in both
      patient groups were maintained during the therapy. Neither fasting nor post
      glucose load venous plasma glucose levels were altered in either group of
      patients, and no patients with normal glucose tolerance developed diabetes
      mellitus during the study. Serum lipid levels did not change significantly in
      either group of patients except for significant decreases in high-density
      lipoprotein cholesterol and apolipoprotein A-I in the group with normal glucose
      tolerance tests, but those changes remained within the normal range. Furthermore,
      neither serum lipid nor apolipoprotein levels were altered, even in patients with
      hypercholesterolemia (total cholesterol levels, > 5.69 mmol/L = 220 mg/dL). These
      results suggest that long-term therapy with felodipine may not alter glucose and
      lipid metabolism in hypertensive patients, and felodipine appears to be useful as
      an antihypertensive agent for hypertensive patients with either dyslipidemia or
      impaired glucose metabolism.

PMID- 8282363
TI  - Systemic and renal effects of nifedipine in cyclosporine-associated hypertension.
AB  - Cyclosporine induces hypertension and wide-spread vasoconstriction after
      transplantation in addition to reducing kidney function. We studied hemodynamic,
      renal, and hormonal effects of monotherapy with nifedipine XL (n = 37) in liver
      transplant recipients within a year after transplant (median, 4.4 months).
      Systemic hemodynamics were determined with thoracic electrical bioimpedance.
      Blood pressure before therapy was 172 +/- 4/108 +/- 2 mm Hg. Sixty-four percent
      of recipients achieved blood pressures less than 140/90 mm Hg mediated by a fall
      in systemic vascular resistance index (2427 +/- 245 dyne.s.cm-5.m-2 in responders
      versus 2905 +/- 281 in nonresponders, P < .01). Despite the fall in systemic
      vascular resistance, glomerular filtration rates were not changed during
      nifedipine therapy, as measured by both creatinine and iothalamate clearances.
      Urinary prostacyclin (6-ketoprostaglandin F1 alpha) was suppressed below normal
      from 2468 +/- 323 ng/d before transplant to 1103 +/- 99 ng/d (P < .01) after
      transplant and did not change during nifedipine therapy. Urinary thromboxane B2
      and plasma renin activity also fell after transplant and remained low during
      nifedipine. These data demonstrate that nifedipine can reverse systemic
      vasoconstriction associated with hypertension after transplantation. Systemic
      effects were not transmitted to the kidney sufficiently to improve glomerular
      filtration rate or reverse hormonal changes within the kidney. Hence, vascular
      and functional regulation of the kidney was dissociated from the systemic
      circulation during nifedipine administration after transplantation.

PMID- 8282364
TI  - Renal response to amino acid infusion in essential hypertension.
AB  - In the present study, we evaluated the renal response to a 4-hour infusion of
      amino acids in essential hypertensive patients, as well as the effects that
      dietary sodium restriction and enalapril (a converting enzyme inhibitor) had on
      this renal response. During normal sodium intake, amino acid infusion
      significantly increased renal plasma flow from 383 +/- 58 to 478 +/- 51 mL/min
      and glomerular filtration rate from 82 +/- 8 to 100 +/- 13 mL/min. All these
      effects were abolished when the patients received a low sodium diet (40 mmol/d)
      for 3 days before the amino acid infusion. The administration of enalapril to the
      patients during sodium restriction restored the amino acid-induced increment in
      renal plasma flow (from 388 +/- 35 to 573 +/- 48 mL/min) and glomerular
      filtration rate (from 88 +/- 9 to 103 +/- 10 mL/min). Mean arterial pressure
      remained unaltered under all experimental conditions. The results show that in
      patients with essential hypertension dietary sodium restriction prevents amino
      acid-induced increments in glomerular filtration rate and renal plasma flow and
      that this effect is restored during the simultaneous administration of enalapril.

PMID- 8282365
TI  - Atrial and brain natriuretic peptides in cardiovascular diseases.
AB  - The human heart secretes both atrial natriuretic peptide and brain natriuretic
      peptide. This study attempts to clarify the pathophysiological significance of
      the peptides in cardiovascular diseases. Using immunoradiometric assay, plasma
      brain natriuretic peptide and atrial natriuretic peptide levels in essential
      hypertension, various secondary hypertension, chronic renal failure, chronic
      heart failure during cardiac pacing, and acute myocardial infarction were
      determined. Mean plasma brain natriuretic peptide and atrial natriuretic peptide
      levels in healthy subjects were 3.7 +/- 0.3 and 5.7 +/- 0.3 pmol/L, respectively,
      and increased as a function of age. Plasma brain natriuretic peptide levels
      showed a larger increase than atrial natriuretic peptide levels in various
      cardiovascular diseases. In chronic renal failure, whereas plasma atrial
      natriuretic peptide levels decreased significantly after hemodialysis and were
      correlated with the changes in body weight, changes in plasma brain natriuretic
      peptide levels were less prominent and did not show such a correlation. In
      chronic heart failure, both basal plasma brain natriuretic peptide and atrial
      natriuretic peptide levels were also significantly elevated. However, in response
      to acute ventricular or atrial pacing, brain natriuretic peptide levels did not
      show any increase in contrast to the marked increase of atrial natriuretic
      peptide levels. In acute myocardial infarction, brain natriuretic peptide levels
      showed more prominent changes than atrial natriuretic peptide levels and were
      correlated with serum levels of creatine kinase and cardiac myosin light chain I
      in most patients. These results suggest that both brain and atrial natriuretic
      peptides play an important role in the regulation of cardiovascular
      homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282366
TI  - Effects of a metalloendopeptidase-24.15. Inhibitor on renal hemodynamics and
      function in rats.
AB  - N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB), an
      active-site-directed inhibitor of metalloendopeptidase-24.15, has been shown to
      lower blood pressure, increase cardiac output and renal blood flow, and
      potentiate the intravenous bradykinin-induced vasodepressor response. Because in
      vivo cFP-AAF-pAB can be converted to N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala
      (a compound with angiotensin converting enzyme inhibitory activity) by
      metalloendopeptidase-24.11, it is possible that some of its effects are due to
      angiotensin converting enzyme inhibition. In the present study, we questioned (1)
      whether cFP-AAF-pAB inhibits angiotensin converting enzyme in vivo and (2)
      whether cFP-AAF-pAB has renal effects that are independent of its conversion to
      an angiotensin converting enzyme inhibitor. cFP-AAF-pAB alone (3 mumol in 300
      microL per rat) almost abolished the blood pressure response to angiotensin I,
      suggesting that in vivo it inhibits angiotensin converting enzyme. In rats
      pretreated with a high dose of enalaprilat (1 mg/kg), cFP-AAF-pAB had no further
      effect on blood pressure, renal blood flow, or potentiation of the vasodepressor
      response to bradykinin but still increased glomerular filtration rate by 44 +/-
      9% (P < .01); urine volume increased by 118 +/- 10% (P < .001), urinary sodium
      excretion by 230 +/- 31% (P < .001), urinary potassium excretion by 68 +/- 14% (P
      < .01), and urinary cyclic GMP by 55 +/- 18% (P < .01). All of these changes were
      significant compared with enalaprilat/vehicle-treated rats. Fractional excretion
      of sodium and potassium did not differ from controls.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8282367
TI  - Dopaminergic abnormalities in hypertension associated with moderate renal
      insufficiency.
AB  - To evaluate the additive effect of moderate chronic renal failure to the abnormal
      dopamine generation and action observed in stable hypertension, we investigated
      22 age-matched patients with a comparable degree of hypertension with and without
      chronic renal failure. Both groups were compared with each other and with an age
      matched control group after a single oral dose of dihydroxyphenylalanine (DOPA)
      while cardiorenal responses and DOPA, dopamine, and their metabolites were
      measured. The hypertensive patients with chronic renal failure shared with their
      hypertensive counterparts without chronic renal failure an impaired DOPA
      decarboxylation to dopamine. However, patients with chronic renal failure had
      decreased hemodynamic and normal natriuretic responses compared with the
      hypernatriuresis of hypertensive patients with normal renal function; patients
      with chronic renal failure had elevated basal plasma concentrations of DOPA and
      dopamine sulfates as well as increased plasma and urinary DOPA sulfate but
      blunted urinary dopamine sulfate increases after DOPA administration; they
      presented augmented plasma atrial natriuretic factor concentrations. Thus,
      hypertensive patients with moderate chronic renal failure exhibit a decreased
      hemodynamic responsiveness to DOPA administration-induced dopamine elevation but
      with the natriuretic effect of dopamine maintained (possibly because of its
      permissive interaction with increased atrial natriuretic factor levels).
      Hypertensive patients with chronic renal failure have a heightened DOPA and
      dopamine sulfoconjugating propensity. Dopamine sulfate attenuates the biologic
      action of free dopamine. This may contribute (possibly via glomerular
      hypertension and hyperfiltration due to decreased postglomerular vasodilation) to
      progressive hypertensive renal damage, particularly in groups predisposed to
      dopamine deficiency, such as diabetics, blacks, and the elderly.

PMID- 8282368
TI  - Pressor mechanisms in adriamycin-induced nephropathy with hypertension in rats.
AB  - We explored the role of angiotensin II and vasopressin in the maintenance of
      blood pressure during the nephrotic syndrome of adriamycin-induced nephropathy in
      rats. All 91 rats treated with adriamycin developed chronic renal failure with
      nephrotic syndrome, which was more pronounced in the normotensive rats than the
      35% who became hypertensive. Angiotensin II blockade with DuP 753 produced a
      significantly greater hypotensive response in both the adriamycin-hypertensive (
      16 +/- 3 mm Hg) and adriamycin-normotensive (-14 +/- 5 mm Hg) groups than the
      saline-treated controls (-5 +/- 1 mm Hg, P < .05). Vasopressin blockade with
      either a V1V2 inhibitor or a selective V1 inhibitor produced a hypotensive
      response in adriamycin-hypertensive rats only (by -16 +/- 4 and -17 +/- 2 mm Hg,
      respectively, P < .01), although the nonselective vasopressin inhibitor produced
      similar fluid loss and body weight reduction in all three groups. The data
      suggest that in adriamycin-induced nephropathy with nephrotic syndrome,
      angiotensin II contributes to blood pressure maintenance in both hypertensive and
      normotensive animals, whereas the pressor action of vasopressin contributes to
      elevated blood pressure in hypertensive animals only.

PMID- 8282369
TI  - Oxytocic effect of trypsin on the isolated rat uterus.
AB  - To study the oxytocic effect of trypsin, we measured the force of isometric
      contraction in uteri isolated from estrogenized rats exposed to trypsin (8.8 x
      10(-10) to 1.7 x 10(-6) mol/L) either alone or in the presence of receptor
      antagonists to angiotensin II [saralasin ([Sar1,Ala8]angiotensin II) or DuP 753
      (losartan)] or to kinins (D-[Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin). We found that
      saralasin or DuP 753, but not the kinin antagonist, displaced the dose-response
      curve to the right. Exposure to exogenous angiotensin I desensitized the
      preparation to further doses of either angiotensin I or II or trypsin, without
      altering the effects of oxytocin or bradykinin. Enalaprilat (an angiotensin I
      converting enzyme inhibitor) or pepstatin A (a renin inhibitor) also displaced
      the dose-response curve to trypsin to the right, without altering the effects of
      oxytocin or angiotensin II. Our results indicate that the response to trypsin is
      mediated by an agent produced from a substrate present in the uterus and acting
      on the angiotensin II type 1 receptor and are consistent with both renin and
      angiotensin I converting enzyme being involved in its mechanism of action, thus
      supporting the notions that the renin-angiotensin system may be important in the
      late stages of pregnancy and that serine proteases existing in the uterus may
      contribute to its activation.

PMID- 8282370
TI  - Familial hypertension and albuminuria in normotensive type I diabetic patients.
AB  - An inherited predisposition to hypertension may increase susceptibility to
      nephropathy in type I diabetes. We evaluated the influence of a family history of
      essential hypertension on albuminuria in normotensive, normoalbuminuric type I
      diabetic patients. Forty-two diabetics (12.9 +/- 2.04 years) were divided into
      three groups according to tertiles of albumin excretion rate (group 1, 1.27 +/-
      0.35; group 2, 2.43 +/- 0.49; group 3, 6.37 +/- 3.43 micrograms/min; P < .001).
      Familial hypertension was considered to be present if the patient had one parent
      or grandparent on antihypertensive therapy. The three groups did not differ
      concerning age, diabetes duration, insulin requirement, body mass index, blood
      pressure, and urinary glucose excretion. Albumin excretion rate did not correlate
      with any parameter studied. The frequency of hypertension was significantly lower
      among the relatives of the patients from group 1 compared with those from groups
      2 and 3 (28.6% versus 64.3% versus 78.6%, P < .03). Our data suggest that a
      familial antecedent of hypertension in normoalbuminuric type I diabetic patients
      is associated with a high normal albumin excretion rate not related to increases
      in blood pressure. Early changes in renal hemodynamics, seen in patients with a
      predisposition to hypertension, may contribute to increments in albuminuria even
      within the normal range.

PMID- 8282371
TI  - Role of hypertension in asymptomatic cerebral lacunae in the elderly.
AB  - To assess the role of hypertension in asymptomatic cerebral lacunae, we evaluated
      cranial computed tomography in 76 untreated hypertensive patients, 173
      hypertensive patients treated with antihypertensive drugs, and 69 age-matched
      normotensive control subjects who were more than 60 years of age and without a
      history of stroke. Cerebral lacunae were diagnosed by computed tomography as a
      hypodense lesion less than 15 mm in diameter seen on a single 10-mm scan section.
      The factors contributing to lacunae were determined by stepwise discriminant
      analysis. Single or multiple cerebral lacunae were revealed in 27.6% (21 of 76)
      of untreated hypertensive patients, 17.3% (30 of 173) of treated hypertensive
      patients, and 7.2% (5 of 69) of normotensive control subjects. Incidence of
      lacunae was significantly higher in hypertensive patients than normotensive
      control subjects. Stepwise discriminant analysis showed that the most strongly
      contributing factor for lacunae was the grade of hypertensive retinopathy in
      untreated hypertensive patients and mean blood pressure in treated hypertensive
      patients. Asymptomatic cerebral lacunae were frequently detected by computed
      tomography in elderly patients with essential hypertension. The severity and
      duration of hypertension correlate positively with this type of vascular
      complication in hypertension.

PMID- 8282372
TI  - Insulin sensitivity and the effects of insulin on renal sodium handling and
      pressor systems in essential hypertensive patients.
AB  - Insulin resistance and hyperinsulinemia are linked with essential hypertension.
      To clarify insulin sensitivity in Japanese essential hypertensive patients and
      the role of insulin resistance in these patients, a euglycemic hyperinsulinemic
      glucose clamp was applied in 17 essential hypertensive patients and 12
      normotensive subjects. The mean glucose infusion rate was used as an indicator of
      insulin sensitivity (M value). This study revealed a significantly lower M value
      in essential hypertensive patients than in normotensive subjects. Increased
      plasma norepinephrine, renin activity, and aldosterone levels were observed after
      hyperinsulinemia for 120 minutes after glucose clamp in normotensive subjects and
      essential hypertensive patients. Urinary sodium excretion and fractional
      excretion of sodium were decreased in essential hypertensive patients as well as
      normotensive subjects during glucose clamp compared with the period before
      glucose clamp. No difference in the percent change was observed between essential
      hypertensive patients and normotensive subjects. These results indicate that
      selective insulin resistance with respect to glucose metabolism exists in
      essential hypertensive patients and that insulin action on renal sodium handling
      and pressor systems was maintained in these patients.

PMID- 8282373
TI  - Nitric oxide influences blood flow distribution in renovascular hypertension.
AB  - Endothelium-derived nitric oxide contributes to the regulation of regional blood
      flow. Inhibition of endothelium-derived nitric oxide synthesis increases blood
      pressure and vascular resistance. Using the substrate antagonist N omega-nitro-L
      arginine-methyl ester to block endothelium-derived nitric oxide synthesis, we
      tested the hypothesis that, in two-kidney, one clip renovascular hypertension,
      endothelium-derived nitric oxide plays an increased role in maintaining blood
      flow to the nonclipped kidney and other visceral organs compared with
      normotensive controls. This could be due to increased vascular shear stress, a
      primary stimulus for endothelium-derived nitric oxide synthesis, after the onset
      of hypertension. In hypertensive rats with mild renal artery stenosis, basal
      renal blood flow normalized by kidney weight was similar in the nonclipped and
      clipped kidneys. Basal blood pressure of controls was 98 +/- 2 mm Hg compared
      with 145 +/- 3 mm Hg in the two-kidney, one clip hypertensive rats. N omega-nitro
      L-arginine-methyl ester increased blood pressure by 20 +/- 2 and 43 +/- 3 mm Hg
      in control and hypertensive rats, respectively. Compared with normotensive
      controls, basal resistance was higher in all organ beds in the hypertensive rats
      including brain, heart, intestine, and kidney. With the exception of the renal
      circulation, the increase in vascular resistance after N omega-nitro-L-arginine
      methyl ester was greater in hypertensive rats compared with normotensive
      controls. In the hypertensive rats, N omega-nitro-L-arginine-methyl ester caused
      a similar increase in vascular resistance in both the nonclipped and clipped
      kidneys, and this was not different from normotensive controls.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8282374
TI  - Nitric oxide participates in calcium-mediated regulation of renin release.
AB  - The regulation of renin release is unusual in that intracellular calcium
      reportedly acts as an inhibitory second messenger. Increased calcium not only
      inhibits renin release but is a cofactor in nitric oxide synthesis. Also, nitric
      oxide can inhibit renin release. This study was done in vitro using rat renal
      cortical slices to determine whether calcium-mediated renin inhibition could be
      in part due to the concurrent production of nitric oxide. Renin concentration in
      the incubation medium was determined by radioimmunoassay for angiotensin I (Ang
      I) generation (in nanograms Ang I per hour per milligram per 30 minutes of
      incubation). In all studies, n = 6 to 17. In normal-calcium incubation medium
      (2.6 mmol/L), 10(-4) mol/L NG-monomethyl L-arginine, which blocks nitric oxide
      synthesis, caused an 18% increase in basal renin release (78.6 +/- 8.9 versus
      66.7 +/- 5.8 [ng Ang I/h]/mg per 30 minutes incubation, P < .05). When calcium
      was eliminated from the incubation medium, basal renin release doubled (to 133.1
      +/- 15.2 [ng Ang I/h]/mg per 30 minutes incubation, P < .001). Without calcium,
      inhibiting nitric oxide synthesis had no further effect on renin release (126.8
      +/- 17.7 [ng Ang I/h]/mg per 30 minutes incubation). High-calcium medium (7.8
      mmol/L) reduced basal renin release by half (30.8 +/- 4.8 [ng Ang I/h]/mg per 30
      minutes incubation, P < .001), but inhibiting nitric oxide synthesis in high
      calcium medium stimulated renin release by 50% (46.9 +/- 6.2 [ng Ang I/h]/mg per
      30 minutes incubation, P < .005). Addition of the calmodulin inhibitor W-7
      completely reversed the inhibition of renin by high-calcium medium.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8282375
TI  - Role of nitric oxide in the renin and heart rate responses to beta-adrenergic
      stimulation.
AB  - Studies in vitro and in vivo have implicated nitric oxide in the control of renin
      secretion. In the present study, the effect of inhibition of nitric oxide
      synthesis with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) on the
      renin secretory response to beta-adrenergic stimulation was investigated in
      conscious, chronically prepared rabbits. Intravenous infusion of isoproterenol at
      0.02 microgram.kg-1 x min-1 for 30 minutes increased mean arterial pressure by 5
      mm Hg (P < .05), heart rate by 51 beats per minute (P < .001), and plasma renin
      activity by 56% (P < .001). Intravenous infusion of L-NAME at 0.5 mg.kg-1 x min-1
      increased mean arterial pressure by 6 mm Hg (P < .01) and decreased heart rate by
      15 beats per minute (P < .01) and plasma renin activity by 31% (P < .05). L-NAME
      reduced the heart rate response to isoproterenol by 50% and inhibited the renin
      response. Infusion of isoproterenol at 0.05 microgram.kg-1 x min-1 did not change
      blood pressure but increased heart rate by 62 beats per minute (P < .001) and
      plasma renin activity by 283% (P < .001). Treatment with L-NAME again suppressed
      the heart rate response to isoproterenol and inhibited the renin response.
      Intravenous infusion of the nitric oxide donor nitroprusside at 2 micrograms.kg
      1.min-1 in the presence of L-NAME decreased mean arterial pressure by 7 mm Hg (P
      < .05), increased heart rate by 14 beats per minute (P < .05), but did not change
      plasma renin activity. Nitroprusside fully restored the heart rate response to
      isoproterenol and partially restored the renin response.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8282376
TI  - Removal of endothelium-dependent relaxation by antibody and complement in
      afferent arterioles.
AB  - Studies of endothelial regulation of microvascular function have been hampered by
      the technical difficulty of removing the endothelium without damaging the
      vascular smooth muscle cells. This study presents a novel method of endothelial
      damage and lysis based on the facts that endothelial cells express specific
      antigens and that complement reacts with antibody/antigen complexes, causing cell
      lysis. We isolated and perfused rabbit glomerular afferent arterioles in vitro
      and examined vascular responses before and after treating them with an antibody
      against factor VIII-related antigen and complement. The treatment consisted of
      perfusing afferent arterioles with medium containing the antibody and complement
      for 10 minutes, followed by a 20-minute washout period. Before treatment,
      acetylcholine and the calcium ionophore A23187 (receptor- and nonreceptor
      mediated endothelium-dependent vasodilators, respectively) dilated norepinephrine
      preconstricted afferent arterioles, whereas neither dilated the arterioles after
      treatment, suggesting loss of endothelium-dependent vasodilation. In contrast,
      responses to nicardipine and norepinephrine (endothelium-independent vasodilator
      and constrictor, respectively) were not altered by the treatment, indicating
      intact vascular smooth muscle cell function. Transmission electron microscopy
      revealed that the antibody- and complement-treated arterioles had various degrees
      of endothelial damage, including areas of detachment from the basement membrane
      and marked loss of the number and structure of mitochondria, but no evidence of
      vascular smooth muscle cell damage. These results indicate that treatment with
      anti-factor VIII-related antigen antibody and complement is an effective method
      for eliminating endothelium-dependent vasodilation without altering endothelium
      independent responses. Thus, this method may be useful for studying the
      functional role of the endothelium in microvessels.

PMID- 8282377
TI  - DuP 753 is more effective than captopril on baroreceptor function in high-renin
      hypertension.
AB  - High-renin hypertensive rats exhibit a general impairment of the baroreceptor
      reflexes. In the present study we compared the effect of the angiotensin
      converting enzyme inhibitor captopril (10 mg/kg per day) with the effect of the
      selective angiotensin subtype 1 receptor blocker DuP 753 (10 mg/kg per day) on
      the baroreceptor reflex bradycardia (progressive doses of phenylephrine) and
      baroreceptor reflex tachycardia (progressive doses of nitroprusside) in conscious
      rats 7 days after aortic ligation. Arterial pressure was markedly reduced after
      both acute (15-minute) treatment with captopril (123 +/- 6 versus 184 +/- 23 mm
      Hg) and DuP 753 (140 +/- 10.5 versus 181 +/- 5.4 mm Hg), but the depressed
      baroreceptor reflex bradycardia increased only after DuP 753 (1.13 +/- 0.22
      versus 0.75 +/- 0.60 beats per minute [bpm]/mm Hg) and remained attenuated after
      captopril (0.54 +/- 0.086 versus 0.30 +/- 0.07 bpm/mm Hg). After a 2-day
      treatment, captopril reduced arterial pressure (95 +/- 5 versus 184 +/- 2.3 mm
      Hg) to lower levels than DuP 753 (119 +/- 6 versus 172 +/- 4.6 mm Hg), whereas
      the depressed baroreceptor reflex bradycardia remained unchanged with captopril
      (0.46 +/- 0.13 versus 0.31 +/- 0.076 bpm/mm Hg) and increased with DuP 753 (1.13
      +/- 0.19 versus 0.38 +/- 0.12 bpm/mm Hg). Neither DuP 753 nor captopril
      administered acutely (15 minutes) or for 2 days significantly altered the
      depressed baroreceptor reflex tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282378
TI  - Chronic converting enzyme inhibition facilitates baroreceptor resetting to
      hypertensive levels.
AB  - We investigated the acute and chronic effects of converting enzyme inhibitors
      (captopril or enalapril) and of angiotensin II receptor blockade (DuP 753) on
      rapid (30-minute) baroreceptor resetting elicited by a prompt and sustained
      hypertensive response provoked by aortic constriction. Pressure-nerve activity
      curves, pressure at 50% of maximal baroreceptor activity, baroreceptor gain
      (slope of the curve), and systolic threshold pressure for baroreceptor activation
      were determined as indexes of baroreceptor function. A slight fall in mean
      arterial pressure after acute treatment with the converting enzyme inhibitor or
      DuP 753 was accompanied by a partial leftward curve shift, which is associated
      with a partial threshold shift and increase in gain. A maintained hypertensive
      stimulus caused a partial rightward curve shift and partial (49% to 56%)
      threshold shift to hypertensive levels in both acutely treated and control rats.
      The hypertensive stimulus provoked a partial rightward curve shift and complete
      (88% to 94%) threshold shift to hypertensive levels in chronically treated rats.
      The effect of enalapril on baroreceptor function was unaltered by the bradykinin
      antagonist Hoe 140. These data demonstrate that chronic inhibition of converting
      enzyme or blockade of angiotensin II receptors facilitates rapid resetting of the
      baroreceptors to hypertensive levels caused by partial aortic constriction
      without a change in baroreceptor sensitivity.

PMID- 8282379
TI  - Physiopathogenesis of acute aortic coarctation hypertension in conscious rats.
AB  - We investigated the role of vasopressin, angiotensin II, and catecholamines in
      the onset of acute (45-minute) aortic coarctation hypertension in conscious rats.
      Partial aortic constriction was performed by means of a pneumatic cuff placed
      around the abdominal aorta above the renal arteries for 15 or 45 minutes. A sham
      operated group was used as control. Mean carotid pressure before aortic
      constriction did not differ between rat groups. Aortic constriction produced a
      similar increase of mean carotid pressure during 15 minutes (36 +/- 3 to 37 +/- 3
      mm Hg above basal levels) and 45 minutes (37 +/- 2 to 39 +/- 3 mm Hg). Plasma
      vasopressin concentration after 15 minutes of coarctation (4.4 +/- 0.5 pg/mL) did
      not differ from that observed in control rats (3.0 +/- 0.8 pg/mL), whereas after
      45 minutes, it was significantly higher (14.3 +/- 3.3 pg/mL). Plasma renin
      activity increased significantly after coarctation (21.7 +/- 4.1 and 29.9 +/- 2.9
      ng angiotensin I/mL per hour, at 15 and 45 minutes, respectively) when compared
      with control rats (3.9 +/- 0.5 ng angiotensin I/mL per hour). After coarctation,
      plasma norepinephrine concentration was consistently reduced, whereas plasma
      epinephrine concentration did not differ from control rats. In conclusion, these
      data provide evidence for an effective vasopressor role for vasopressin in the
      genesis of acute (45-minute) aortic coarctation hypertension in conscious rats.
      In addition, although the results confirm that the renin-angiotensin system
      participates earlier in the onset of coarctation hypertension, they rule out a
      significant vasopressor role for catecholamines in the early development of
      hypertension.

PMID- 8282380
TI  - Abnormal pressure natriuresis in the dog model of obesity-induced hypertension.
AB  - Obesity is considered to be a major factor in the pathogenesis of hypertension in
      industrialized countries. Recent studies have suggested that the kidneys may play
      an important role in the development of obesity-induced hypertension. The purpose
      of this study was to determine whether obesity-induced hypertension is associated
      with abnormalities in the pressure-natriuresis relation. Renal function studies
      were performed in anesthetized control dogs (body weight, 20.2 +/- 0.8 kg) and
      obese dogs (body weight, 26.4 +/- 0.7 kg) that were maintained on a high-fat diet
      for 5 to 6 weeks. Mean arterial pressure averaged 122 +/- 5 mm Hg in the control
      group (n = 6) and 148 +/- 7 mm Hg in the obese group (n = 8). The effects of
      renal perfusion pressure on renal hemodynamics as well as sodium and water
      excretions were examined at five levels of renal perfusion pressure ranging from
      75 to 165 mm Hg. Pressure-natriuretic and diuretic responses were reduced in the
      obese dogs by 40% to 50%. The renal blood flow and glomerular filtration rate
      autoregulatory responses and fractional lithium excretion responses to changes in
      renal perfusion pressure were similar in the control and obese dog groups.
      Associated with the attenuated natriuretic response to renal perfusion pressure
      in the obese dogs were significant elevations in plasma renin activity (4.3 +/-
      1.6 versus 1.6 +/- 0.5 ng angiotensin I/mL per hour), plasma aldosterone
      concentration (34.4 +/- 6.4 versus 15.3 +/- 3.2 ng/dL), and plasma insulin
      concentration (30.5 +/- 6.8 versus 20.9 +/- 2.9 IU/mL).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8282381
TI  - Effects of age and hypertension on autonomic nervous regulation during passive
      head-up tilt.
AB  - To study the effects of age and hypertension on autonomic nervous function with
      passive postural change, we examined 31 normotensive subjects (25 to 85 years
      old) and 31 hypertensive patients (21 to 71 years old) without any cardiac
      disease, diabetes mellitus, or neurological disorders. Subjects were passively
      placed in a 60 degrees head-up tilting position after 15 minutes in the supine
      position. Autonomic nervous function was evaluated by frequency domain analysis
      of heart rate with the autoregressive method. Using low-frequency (0.1 Hz) and
      high-frequency (0.25 Hz) peaks, the ratio of low- to high-frequency power (L/H)
      was calculated as an index of sympathetic activity and the ratio of high to total
      power (%HF) as that of parasympathetic activity. With the patient in the supine
      position, total power spectral density declined logarithmically with age in
      normotensive subjects and hypertensive patients, but %HF and L/H showed no
      changes. In response to passive tilting, L/H was increased and %HF was decreased
      in the normotensive subjects, and these responses declined with age
      logarithmically. In contrast, hypertensive patients exhibited less autonomic
      response to postural change regardless of age. These results suggest that
      autonomic neural response to tilt is decreased with age; however, attenuation of
      the response by hypertension is not associated with an increase in age.

PMID- 8282382
TI  - Time course of changes in sigmoidal-fitting baroreceptor curves in one-kidney,
      one clip hypertensive rats.
AB  - The present study examined the time course of changes in baroreceptor reflex
      function by means of sigmoidal curve-fitting analysis in conscious, unrestrained
      renovascular one-kidney, one clip (1K1C) rats at 1, 3, 7, 15, 30, and 60 days
      after renal artery clipping. The reflex heart rate responses were elicited by
      alternate intravenous bolus injections of phenylephrine (change, +5 to +50 mm Hg)
      and sodium nitroprusside (change, -5 to -50 mmHg). Atropine methylnitrate and
      atenolol were given to evaluate the responses mediated by the cardiac sympathetic
      or vagal component, respectively. The average baroreceptor reflex gain
      (sensitivity) decreased progressively (day 1, 3.35 +/- 0.3 beats per minute [bpm]
      per millimeter of mercury), reaching a maximal attenuation in the 30-day 1K1C
      group (1.83 +/- 0.5 bpm/mm Hg) compared with sham rats (approximately 4.60 bpm/mm
      Hg). The data showed a decreased vagal activity contributing to the attenuation
      of the baroreceptor gain only in the 30-day 1K1C group. In contrast, the cardiac
      sympathetic component of the baroreceptor reflex was significantly decreased in
      all 1K1C groups (from 2.10 +/- 0.4 to 0.50 +/- 0.2 bpm/mm Hg) compared with the
      respective sham groups (from 3.80 +/- 0.3 to 3.10 +/- 0.4 bpm/mm Hg). These
      results suggest that a reduced contribution of the sympathetic component to the
      baroreceptor heart rate reflex may be the main cause of the progressive
      attenuation of the baroreceptor reflex sensitivity observed in conscious 1K1C
      hypertensive rats.

PMID- 8282383
TI  - Alteration of response to neuropeptide Y in the nucleus tractus solitarius of
      spontaneously hypertensive rats.
AB  - In normotensive rats, microinjections of neuropeptide Y (2.5 to 25 pmol) into the
      unilateral nucleus tractus solitarius elicited dose-dependent vasodepressor and
      bradycardiac responses accompanied by an inhibition of sympathetic nerve firing.
      After microinjections of the alpha 2-adrenergic receptor antagonist yohimbine
      (100 ng) into the nucleus tractus solitarius, the depressor and bradycardic
      responses to the injection of neuropeptide Y (25 pmol) into the nucleus tractus
      solitarius were significantly attenuated. In contrast, pretreatment with the
      alpha 1-adrenergic receptor antagonist doxazosin (200 ng) injected into the
      nucleus tractus solitarius did not alter these responses. In spontaneously
      hypertensive rats, microinjections of neuropeptide Y (25 pmol) into the nucleus
      tractus solitarius also elicited depressor and bradycardic responses that were
      significantly less than those of normotensive Wistar-Kyoto rats. However,
      pretreatment with yohimbine (100 ng) in the nucleus tractus solitarius did not
      diminish these depressor responses in spontaneously hypertensive rats. Depressor
      responses to neuropeptide Y, which was administered after yohimbine pretreatment,
      were also less in Wistar-Kyoto rats than in spontaneously hypertensive rats. The
      results suggest that the depressor and bradycardic responses elicited by
      neuropeptide Y were accompanied by the inhibition of sympathetic nerve activity.
      These responses may be mediated in part by alpha 2-adrenergic receptor in the
      nucleus tractus solitarius. The impairment of alpha 2-adrenergic receptor
      mediated responses to neuropeptide Y in spontaneously hypertensive rats may
      contribute to the development of hypertension.

PMID- 8282384
TI  - Neural effects on renal blood flow during acute hypotension vary with
      antihypertensive drugs.
AB  - To examine the neural effects of antihypertensive drugs on renal blood flow, we
      measured blood flow and renal sympathetic nerve activity simultaneously in
      conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to two days
      after surgery, intravenous administration of manidipine (calcium antagonist, n =
      10), doxazosin (alpha 1-adrenergic receptor antagonist, n = 9), and clonidine (n
      = 7) lowered mean arterial pressure by at least 20% from baseline levels.
      Manidipine initiated a reduction of renal blood flow when mean pressure decreased
      by 20 +/- 2 mm Hg. At the maximal decrease in renal blood flow (mean pressure, 
      33 +/- 2 mm Hg), percent decrease in flow (-27 +/- 2%) significantly correlated
      with percent increase in renal nerve activity (+205 +/- 40%, r = -.878).
      Doxazosin began to decrease renal blood flow at a level of arterial pressure
      similar to that in manidipine treatment, whereas the maximal decrease in flow (
      19 +/- 2%; mean pressure, -33 +/- 2 mm Hg; nerve activity, +225 +/- 44%) was
      significantly less than that in manidipine treatment. Although clonidine
      decreased arterial pressure and renal nerve activity, renal blood flow did not
      decrease even at the maximal decrease in mean pressure of 29 +/- 1 mm Hg. The
      addition of clonidine to manidipine treatment suppressed reflexly enhanced renal
      nerve activity and restored blood flow to the pretreatment level despite
      pronounced hypotension. These results clearly demonstrate that antihypertensive
      drugs with blocking action on renal nerve activity are capable of maintaining
      renal blood flow and that those associated with reflex-induced enhancement of
      nerve activity exert deteriorating effects on renal blood flow. Furthermore, a
      decrease in renal blood flow induced by calcium antagonists is mainly attributed
      to reflexly enhanced renal nerve activity.

PMID- 8282385
TI  - Management of childhood acute leukemias: present concepts.

PMID- 8282386
TI  - Child care in India: emerging challenges.

PMID- 8282387
TI  - Isosexual precocity: the clinical and etiologic profile.
AB  - Eighty children (58 girls and 22 boys) with isosexual precocity seen in the past
      eight years were evaluated clinically and investigated to identify the underlying
      cause. Of these, 50% (29 girls and 11 boys) had centrally mediated true
      precocious puberty (TPP). The girls could be classified into five major groups
      (I) Central precocious puberty 29-subclassified into idiopathic (ITPP, 15) and
      organic or neurogenic (NTTP, 14), (II) Premature thelarche (PT, 20), (III)
      Premature menarche (PM, 2), (IV) Premature adrenarche (PA, 5), and, (V) Others:
      hypothyroid (n = 1), and McCune Albright Syndrome (n = 1). ITPP as a cause of
      precocity in girls was seen less often (52%) and NTPP more often (48%) compared
      to most Western series, with tubercular meningitis as the cause in 31% and
      hypothalamic hamartomas in 10%. Though the LH and estradiol levels were
      significantly higher (p < 0.05) in TPP, compared to PT, these were not helpful in
      differentiating because of considerable overlap. LH-predominant-response (LH/FSH
      ratio > 1) to LHRH testing was seen in TPP. Amongst the 22 boys, 11 (50%) had
      TPP, ITPP in 27% and NTPP in 73%. Hamartomas (n = 4) and TBM (n = 3) contributed
      equally to NTPP; pineal tumor was seen in one. The adrenal (n = 7) and testicular
      (n = 2) causes together involved 41% of the boys with precocity, congenital
      adrenal hyperplasia (CAH) CAH, 11-beta hydroxylase being the commonest cause. Of
      the 6 boys witdeficiency was found in four and nonsalt losing form of 21
      hydroxylase deficiency in 2. Testicular and adrenal tumors and testotoxicosis
      were noted in one case each. The etiologic factors were more varied in boys.

PMID- 8282388
TI  - Evaluation of radionuclide gastroesophagography as a suitable screening test for
      detection of gastroesophageal reflux.
AB  - Thirty cases of recurrent pulmonary infection and ten control cases underwent
      radionuclide gastroesophagography endoscopy, histopathology and barium
      esophagography to evaluate the clinical efficacy of scintigraphic technique in,
      detection of gastroesophageal reflux. After ingesting 500 micro curie of Tc
      Sulphur colloid mixed in milk, patients esophageal activity was monitored using
      the gamma camera for forty-five minutes continuously. By using histopathology as
      standard of comparison, the sensitivity and specificity of radionuclide
      esophagography was 78.54 and 81.25%, respectively. Because of its physiologic
      nature, low radiation exposure and convenience, radionuclide esophagography is
      recommended as a suitable screening test for detecting gastroesophageal reflux
      where available.

PMID- 8282389
TI  - Simple approach to acute respiratory infection in rural under five children.
AB  - The feasibility of acute respiratory infection (ARI) control in 5,535 rural
      preschool children was studied. The Primary Health Centre (PHC) staff and local
      practitioners (drug distribution centres) were identified and trained in
      recognition of moderate/severe ARI, referral, drug administration and in the
      education of the community. Functional ARI classification as envisaged in ARI
      control programme was followed. There was significant reduction in moderate (42%
      reduction) and severe (89% reduction) ARI episodes from year 1985 to 1987. Both
      ARI (27.8%) and non-ARI (18.3%) deaths showed reduction. Majority of children who
      died due to ARI were also unimmunized. The moderate and severe ARI related
      morbidity and mortality was significantly reduced in immunized children compared
      to unimmunized children. Although, strategies of National ARI control programme
      by health education, standard case management and strengthening of immunization
      is a good thought but it is clear that proper implementation of immunizations is
      going to pay more dividends. It is also evident that the local medical
      practitioners should be trained and involved in this control programme to have
      community faith as well as to avoid opposition.

PMID- 8282390
TI  - Role of phenobarbitone in preventing recurrence of febrile convulsions.
AB  - A randomized double blind placebo controlled trial was carried out to study the
      effect of phenobarbitone (PB) in preventing recurrences of simple and atypical
      febrile convulsions among children in the age group 6 months to 6 years. Children
      with simple febrile convulsions were randomly allocated to receive either
      phenobarbitone or placebo. Children with atypical convulsions were treated with
      phenobarbitone, as a third group. Thirty children were admitted in each group.
      All the children were followed up for a period of twelve months. Recurrence of
      convulsions and side effects of PB were recorded. Recurrence occurred in only 7%
      (95% confidence interval: 1-22) of children on Phenobarbitone, suffering from
      either simple or atypical febrile convulsions, compared to 53% (95% confidence
      interval: 34-72) of children on placebo, suffering from simple febrile
      convulsions. With Phenobarbitone, 5% of children had intolerable side effects.
      These results suggest that long term prophylaxis with phenobarbitone, even in
      simple febrile convulsions will be useful.

PMID- 8282391
TI  - Duodenal string test in typhoid fever.
AB  - Twenty five children between 4-12 years of age hospitalized with a clinical
      diagnosis of enteric fever were studied for evaluating the practicality and
      sensitivity of duodenal string-capsule culture (DSCC) and compared with
      conventional cultures from blood (BC), urine (UC) and stool (SC). Duodenal string
      capsule (DSCC) was successfully inserted in 18 patients (72%). Insertion of DSCC
      failed in 7 patients (28%) and all of them were below 6 years of age. Salmonella
      typhi was isolated from DSCC and/or BC in 13 cases (72.2%). DSCC was positive in
      11 out of 13 confirmed cases of typhoid fever (84.6%). BC was positive in 8 cases
      (61.5%). DSCC was successful in isolating the organism in about 30% more cases
      than BC. Duodenal string test was a simple, non-invasive and a reliable test
      which when used in combination with BC could identify almost all cases of enteric
      fever irrespective of duration of fever and prior use of antibiotics.

PMID- 8282392
TI  - Breastfeeding and childhood cancer.
AB  - Total duration of breastfeeding and of exclusive breastfeeding was studied and
      compared in 99 childhood cancer cases and 90 controls. The difference between the
      average duration of breastfeeding in cases and controls was significant (p <
      0.05), but when average duration of exclusive breastfeeding was compared in cases
      and controls the difference was highly significant (p < 0.001). In lymphoma cases
      and controls the difference between the average duration of breastfeeding was
      moderately significant (p < 0.01). However, when average duration of exclusive
      breastfeeding was compared in lymphoma cases and controls the difference was
      highly significant (p < 0.001). When other cancer groups and controls were
      compared with respect to their total duration of breastfeeding and duration of
      exclusive breastfeeding the differences when insignificant (p > 0.05). Cases and
      controls were not different with respect to their age, sex, birth year, birth
      order, age and educational status of mothers, smoking of fathers and
      socioeconomic status. However, a positive family history of cancer was obtained
      in 4 (4%) of cases whereas in controls it was obtained in only 1 (1.1%).

PMID- 8282393
TI  - Body stalk anomaly.

PMID- 8282394
TI  - WAGR complex.

PMID- 8282395
TI  - Congenital mesangioproliferative nephrotic syndrome associated with
      cytomegalovirus infection.

PMID- 8282396
TI  - Prevalence of xerophthalmia in pre-school children in an urban slum.

PMID- 8282397
TI  - Maternal beliefs regarding diet during acute diarrhea.

PMID- 8282398
TI  - Intrarenal neuroblastoma presenting as orbital and multiple skeletal metastases.

PMID- 8282399
TI  - Cystic tuberculosis of bones.

PMID- 8282400
TI  - Cohen syndrome.

PMID- 8282401
TI  - Knowledge of community based practitioners regarding vaccine preventable
      diseases.

PMID- 8282402
TI  - Down's syndrome with Hodgkin's disease.

PMID- 8282404
TI  - Hydatid cyst in an adolescent boy.

PMID- 8282403
TI  - Teratomas in pediatric age group: experience with 75 cases.
AB  - The clinicopathological features of 75 children under the age of 12 years with
      teratomas are reviewed. Tumors arose in the following anatomic sites:
      sacrococcygeum (n = 49), ovary (n = 10), Testis (n = 5), oral cavity (n = 3),
      retroperitoneum (n = 2) and others (n = 6). Fifty five (74%) presented within the
      first year of life. Excluding the gonadal tumors, male-female ratio was 2:5.
      Majority of the tumors had only mature tissues. Such patients and those 9
      patients in whom the histology was not specified, underwent excision alone and
      had 95% early survival rates. Five patients had admixture of mature and immature
      tumors. Nine patients had malignant tissues. Germ cell tumors containing only
      malignant component, but no mature or immature teratomatous tissues were excluded
      from the series. The patients with immature and malignant tissues underwent
      multimodal therapy including surgical excision, multiagent chemotherapy (VAC
      regimen) and at times radiotherapy. Mortality in patients with immature and
      malignant teratomas was 20 and 66.7%, respectively. Besides histology, the only
      factor which affected prognosis, especially in case of sacrococcygeal teratomas
      was the age at the time of presentation. Our experience highlights the importance
      of early recognition and complete surgical excision of teratomas in the pediatric
      age group.

PMID- 8282405
TI  - Experiences with objective structured clinical examination (OSCE) as a tool for
      formative evaluation in pediatrics.
AB  - Mean scores obtained at objective structured clinical examination (OSCE) and
      clinical case (CC), by 4 groups of 15 students each were compared. The range of
      dispersion was more with OSCE as compared to CC. There was no correlation between
      the scores obtained at OSCE and CC. It is suggested that OSCE can be employed for
      evaluation of specific clinical skills; however, for comprehensive evaluation, a
      combination of OSCE and CC should be used.

PMID- 8282406
TI  - Recommendations of sub-committee constituted by Medical Council of India to
      prepare syllabus in pediatrics for undergraduate medical students.

PMID- 8282407
TI  - Injectable vitamin K and increased risk of childhood cancer.

PMID- 8282408
TI  - Chronic subdural hematoma.

PMID- 8282409
TI  - Visceral leishmaniasis treated with rifampicin and cotrimoxazole.

PMID- 8282410
TI  - P-floxacin induced arthropathy.

PMID- 8282411
TI  - Hepatobiliary complications of enteric fever.

PMID- 8282412
TI  - Work in the cold. Review of methods for assessment of cold exposure.
AB  - The obvious hazard of a cold exposure under natural as well as artificial
      conditions is tissue cooling and the associated sequel of more or less harmful
      effects from cold injury to discomfort. The nature, risk and magnitude of effects
      depend largely on the cooling effect, which results from the interaction of
      climatic factors (air temperature, mean radiant temperature, humidity and wind),
      protection (clothing) and metabolic heat production (activity). Assessment of
      cold stress should be based on methods which measure or predict this cooling
      effect in a relevant and reliable way. The nature of cooling encompasses (1)
      whole-body cooling, (2) extremity cooling, (3) convective cooling (wind chill),
      (4) conductive cooling (contact) and (5) airway cooling. The review contains a
      description of methods for evaluation of the various types of cold stress, as
      well as a discussion of their capacity and limitations. On the basis of selected
      methods, recommendations related to lowest permissible temperatures and other
      measures are discussed and compared with published data. Apparently, local
      cooling in most cases produces discomfort and harmful effects, before more
      significant whole-body cooling develops. With strong wind or movement at very low
      temperature, frostnip of unprotected skin may quickly develop. For most other
      conditions extremity (digit) cooling determines duration of exposure. However, as
      digit cooling largely depends on whole-body heat balance, it is important to
      control body cooling by selection and use of appropriate protective clothing.

PMID- 8282413
TI  - Cytogenetic studies in lymphocytes of workers exposed to 2,3,7,8-TCDD.
AB  - Chromosome aberrations and sister chromatid exchanges (SCEs) were evaluated in 27
      workers with current 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) blood lipid
      concentrations exceeding 40 parts per trillion (ppt) and in 28 unexposed
      referents of similar age. No statistical differences were found between the two
      groups in the percentages of gaps, chromatid or chromosome exchanges, chromatid
      or chromosome breaks/fragments/deletions, multiple aberrations, or the overall
      percentage of aberrations including gaps (1.33% in the exposed group vs 1.75% in
      the referent group) or excluding gaps (0.54% in each group). There was an
      increased rate of SCEs per cell (P = 0.051) and a higher percentage of cells with
      more than 10 SCEs (P = 0.064) in the exposed group; however, these associations
      were no longer significant when smoking status was included as covariate.
      Additionally, neither current nor back-calculated TCDD concentration was a
      significant predictor of these parameters based on multiple linear and rank
      regression analyses.

PMID- 8282414
TI  - Mortality and tumour morbidity among Swedish market gardeners and orchardists.
AB  - In order to investigate possible effects of exposure to pesticides, mainly
      fungicides and insecticides, we studied a cohort of 2370 subjects, who, during
      the period 1965-1982, had been members of a horticulturists' trade association
      (market gardeners and orchardists). Compared to a regional reference population,
      total mortality (542 deaths; standardized mortality morbidity ratio, SMR = 0.8;
      95% confidence limits, CLs = 0.7, 0.9) and mortality due to malignant tumours
      (133 deaths, SMR = 0.9; CLs = 0.7, 1.0), and cardiovascular and respiratory
      deaths were somewhat decreased. Suggestive excesses in mortality were seen for
      mental disorders and tumours of the stomach, skin and nervous system. The tumours
      of the nervous system were in particular excess in the young and middle-aged
      horticulturists (below age 60; six cases, SMR = 2.9; CLs = 1.1, 6.2). During the
      period 1965-1986, the total tumour morbidity was slightly decreased (255 cases;
      SMR = 0.9; CLs = 0.8, 1.0), as were gastrointestinal and respiratory tract
      tumours. The incidence of melanomas was increased (15 cases, SMR = 2.1; CLs =
      1.2, 3.5), and tumours of the female genital organs, myelomas, and brain tumours
      (12 cases, SMR = 1.5; CLs = 0.8, 2.7) were slightly numerically elevated. Brain
      tumours in the young and middle-aged horticulturists (11 cases, SMR = 3.2; CLs =
      1.6, 5.7), including meningiomas (four observed, SMR = 6.8; CLs = 1.9, 17.4),
      were increased, especially in the period 1975-1979. The mortality and tumour
      morbidity patterns in gardeners and orchardists, analysed separately, were
      similar to the patterns in all the horticulturists.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8282415
TI  - Bronchial carcinoma mortality in the German chromate-producing industry: the
      effects of process modification.
AB  - This study updates a 1982 report on mortality at two German chromate-producing
      factories. The main objective of the study was to establish whether the change
      over to a production process using lime-free conversion of chromite ore, thus
      eliminating the formation of calcium chromate, had resulted in a distinct
      reduction in bronchial carcinoma mortality among workers exposed for the first
      time after the change-over (completed in 1958 in Leverkusen and 1964 in
      Uerdingen). A total of 1417 workers with at least 1 year of exposure were
      enrolled in the study. The observation period ended on 31 December 1988. The
      expected number of deaths was calculated using population statistics for North
      Rhine-Westphalia. The risk was determined in the form of a standardised mortality
      ratio (SMR), i.e. the ratio of observed deaths to expected deaths. In the group
      of 739 workers exposed before the process change-over was completed, 432 died
      during the observation period, 66 of them from bronchial carcinoma. This
      significant excess produced an SMR of 2.27 (95% confidence interval: 1.78-2.85).
      Where the cause of death was unknown, cases were allocated to a cause of death on
      the basis of the percentage occurrence of various causes of death in the specific
      subcohort. The cohort of 678 workers first exposed after the process modification
      had been completed had a slightly increased SMR for lung cancer of 1.26 (95%
      confidence interval: 0.58-2.38) based on nine cases.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8282416
TI  - Acute effects of m-xylene inhalation on body sway, reaction times, and sleep in
      man.
AB  - Nine male volunteers were exposed to either a constant or a fluctuating exposure
      pattern of m-xylene with a time-weighted average exposure concentration of 200
      ppm in both cases. The subjects remained sedentary throughout the exposure, or
      the exercised at 100 W for 10 min at the beginning of the morning and the
      afternoon sessions. In another experiment, 12 sedentary male volunteers were
      exposed to a fixed 200 ppm of m-xylene. The effects of m-xylene on body sway,
      reaction time performance, and overnight sleep were measured. Body balance was
      stabilized after exposure to the peaks of 400 ppm of m-xylene in both sedentary
      and exercising subjects. Simple visual reaction times were prolonged after the
      peak exposures at rest whereas auditive choice reaction times were prolonged
      after peaks combined with exercise. Exposure to m-xylene at a constant level of
      200 ppm did not affect the ratio of "active" to "quiet" sleep in the volunteers
      as measured with the static charge sensitive bed recording, but decreased
      slightly the number of body movements in bed. On the next morning no changes were
      found in body sway and reaction time performance as compared to the morning
      before exposure.

PMID- 8282418
TI  - Reference values for blood toluene in the occupationally nonexposed general
      population.
AB  - Blood toluene was measured by gas chromatography--mass spectrometry in 232
      occupationally nonexposed subjects, consisting of 126 rural and 106 urban
      workers, and 37 chemical workers. Mean blood toluene was significantly lower in
      rural (698 ng/l) and urban workers (984 ng/l) than in chemical workers (2789
      ng/l). Blood toluene was not significantly different between the rural and urban
      workers or among the urban workers with different jobs. Smokers had significantly
      higher levels (median 606 ng/l) than nonsmokers (median 424 ng/l). Subjects who
      had smoked at least one cigarette in the last 2 h before blood sampling had
      significantly higher blood toluene (median 1170 ng/l) than those who had not
      smoked during this time (median 693 ng/l), for whom the level was not
      significantly different from that in nonsmokers. Blood toluene in the total
      population was less than 2863 ng/l in 95% cases.

PMID- 8282417
TI  - Biomonitoring of polycyclic aromatic hydrocarbons in highly exposed coke plant
      workers by measurement of urinary phenanthrene and pyrene metabolites (phenols
      and dihydrodiols).
AB  - A filter combination consisting of an impregnated glass fibre and a control
      filter was used for the collection of air samples in which gaseous and
      particulate polycyclic aromatic hydrocarbons (PAHs) were determined. To estimate
      the loss of lower boiling PAHs, d10-phenanthrene was applied as internal
      standard. A simple, well-producible method for the determination of 1-, 2-, 3-, 4
      and 9-hydroxyphenanthrene, 1,2-, 3,4- and 9,10-dihydroxydihydrophenanthrene, 1
      hydroxypyrene and 1,2-dihydroxy-1,2-dihydropyrene is described. By means of
      personal air samplers the exposure to PAHs of four coke plant employees working
      at different locations was measured over 4 days. Simultaneously the 24-h urine
      was collected and stored frozen until analysed. The main excretion product of
      pyrene is a 1-hydroxypyrene conjugate, whereas phenanthrene is excreted
      predominantly as dihydrodiol conjugate. As expected, workers on the battery
      topside were exposed the most and accordingly excreted by far the highest amounts
      of PAHs. Up to 34.0 micrograms phenanthrol conjugates (total of all isomeric
      phenols) and 195.5 micrograms dihydrodiol conjugates (total of all isomeric
      dihydrodiols) were excreted in the 24-h urine (mean of 4 days). The metabolite
      profiles of five isomeric phenanthrene phenols and three isomeric dihydrodiols
      exhibited only small percentage variations within one individual whereas
      significant interindividual differences were observed. These findings may
      indicate a genetically determined enzyme pattern responsible for the metabolic
      conversion of PAHs.

PMID- 8282419
TI  - Road traffic noise around schools: a risk for pupil's performance?
AB  - Noise levels around educational centres can negatively affect the performance of
      both teachers and pupils. Two public schools in Valencia, Spain, were selected
      for study. One of these schools was exposed to excessively high road traffic
      noise levels while the other was located in a relatively quiet area. The
      socioeconomic level of those attending the schools was very similar. A set of
      external and internal noise measurements were carried out, along with two
      different attention tests among the children. Test results were consistently
      better (both for tests and for children from different classrooms in each school)
      in the quiet school. Exposure to high traffic noise levels in the noisy school
      over the whole school year is a plausible determinant of these results.

PMID- 8282420
TI  - Hygiene and health: the value of antiplaque agents in promoting oral health.
AB  - The improvements in human health and increased life expectancy which have come
      about in many societies in the past century have been due, predominantly, to
      improvements in hygiene--both personal and environmental. As the common oral
      diseases--caries and gingivitis and to some extent periodontitis--are bacterially
      mediated diseases, they are also amendable to control by oral hygiene. As
      commonly practised however, with modern diets, mechanical oral hygiene alone has
      limited effect on disease incidence. The supplementation of tooth brushing with
      chemical agents which modulate plaque metabolism and the effects of metabolites
      on the hard and soft tissues of the dento-gingival structures certainly has
      preventive and therapeutic value. This is particularly true of fluoridated
      dentifrices in the control of dental caries, and of dentifrices with
      antibacterial and anticalculus properties, such as those containing low
      concentrations of the phenolic compound Triclosan, in the control of gingivitis.
      Microbial colonisation of tooth and other body surfaces is normal and forms part
      of the natural defence against dangerous exogenous organisms: thus modulating or
      'controlling' plaque, not eliminating it, is the purpose of oral hygiene. The
      goal is to maintain a microbial ecosystem consistently associated with healthy
      tissues.

PMID- 8282421
TI  - Oral delivery and clearance of antiplaque agents from Triclosan-containing
      dentifrices.
AB  - Oral delivery and clearance of Triclosan and zinc were studied following use of
      three commercially available Triclosan-containing toothpastes. One paste
      contained 0.3 per cent Triclosan and 2 per cent PVM-MA copolymer, one contained
      0.3 per cent Triclosan and 5 per cent sodium pyrophosphate and the third
      contained 0.3 per cent Triclosan and 0.75 per cent zinc citrate trihydrate. Each
      gave similar total oral retention of Triclosan (37 per cent-46 per cent of the
      dose). However, clinically important product differences were observed in the
      salivary clearance of Triclosan and in Triclosan delivery to plaque. The
      Triclosan/zinc paste delivered more Triclosan to oral reservoirs (as measured by
      the area under the salivary clearance curve) than either the Triclosan/PVM-MA or
      the Triclosan/pyrophosphate paste (p < 0.001). The Triclosan/zinc paste produced
      higher Triclosan levels in plaque than the Triclosan/PVM-MA paste (109
      micrograms/g versus 78 micrograms/g, p < 0.05). Zinc was effectively delivered to
      oral surfaces by the Triclosan/zinc paste, and was cleared more slowly than
      Triclosan (single-reservoir t1/2 = 50 min). After use of the Triclosan/zinc paste
      the zinc level in plaque was 153 micrograms/g, a seven-fold increase over the
      control. These results demonstrate that good delivery of Triclosan requires a
      highly optimised formulation. Furthermore, they suggest that the superior
      clinical effects of the Triclosan/zinc paste are due to a combination of superior
      delivery of Triclosan to oral sites of action together with effective delivery of
      a second, complementary antiplaque agent, zinc.

PMID- 8282422
TI  - Microbiological effects of new agents in dentifrices for plaque control.
AB  - The incorporation of antimicrobial agents in dental products has been proposed
      for many years as a possible valuable adjunct to mechanical plaque control. Out
      of the diverse collection of potential agents, relatively few can be formulated
      into dentifrices. Several products have been developed based on Triclosan, a
      broad spectrum antimicrobial agent. By itself, Triclosan has only moderate
      antiplaque activities; consequently, it has been combined with other molecules in
      attempts to boost its clinical efficacy. The combination of Triclosan with a
      copolymer (polyvinyl methyl ether maleic acid) has been shown to increase the
      retention of Triclosan to surfaces, and to raise its antiplaque and antimicrobial
      activity in a range of laboratory tests. Other studies, however, have found
      greater inhibitory effects on both liquid and biofilm mixed cultures when
      Triclosan was combined with either pyrophosphate or zinc citrate. Both of these
      combinations were selectively inhibitory to those species implicated in
      gingivitis and advanced periodontal diseases. There is little microbiological
      data on the clinical efficacy of a combination of Triclosan with pyrophosphate,
      but as pyrophosphate has only a bacteriostatic mode of action and is lost rapidly
      from the mouth, this may limit the significance of any of its potential
      antimicrobial effects in vivo. In contrast, zinc citrate is a proven inhibitor of
      bacterial metabolism and growth, and is retained in the mouth for prolonged
      periods. Several clinical studies have confirmed an additive, complementary and
      selective inhibitory antimicrobial effect on dental plaque of a dentifrice
      containing Triclosan and zinc citrate, without any adverse effects on the natural
      microbial ecology of the mouth.

PMID- 8282423
TI  - The caries preventive effect of a fluoride dentifrice containing Triclosan and
      zinc citrate, a compilation of in vitro and in situ studies.
AB  - A new generation of 'gun-health dentifrices' has recently become available. These
      products contain antimicrobial ingredients in addition to fluoride as the caries
      preventive component. Several experiments were performed to study the effects of
      the addition of antimicrobials. These included fluoride bioavailability tests,
      enamel lesion de- and remineralisation studies ('pH-cycling') and in situ caries
      studies. A comparison was made between a non-fluoride (negative) control
      dentifrice, a fluoride (positive) control dentifrice (1000 ppm F as sodium
      monofluorophosphate, MFP) and a test dentifrice containing 1000 ppm F (as MFP),
      0.3 per cent Triclosan and 0.75 per cent zinc citrate trihydrate (ZCT). The
      results showed that the two fluoride pastes performed better in all tests than
      the negative control. No differences were observed between the two fluoride
      pastes in the in vitro studies. Under conditions of cariogenic challenge, in situ
      caries progression was inhibited by the fluoride test paste containing Triclosan
      and ZCT. This result was significantly different from that of the fluoride
      control paste, in which group an increase in lesion severity was observed.

PMID- 8282424
TI  - Chemical plaque control: how do you advise your patients?
AB  - Certain antiplaque and antigingivitis agents have proven efficacious in the
      control of plaque and gingivitis. To adequately assess the magnitude of the
      effect that is to be expected in clinical practice, the dentist must take into
      account the experimental design in order to extrapolate the results of the
      clinical trial to the target patient population. This paper reviews the strengths
      and weaknesses of major clinical trial designs in light of their relationship to
      the results dentists can expect in clinical practice.

PMID- 8282425
TI  - The effect of dentifrices containing Triclosan on the development of gingivitis
      in a 21-day experimental gingivitis study.
AB  - The aim of this study was to investigate the ability of Triclosan dentifrices to
      delay the development of gingivitis during a 21-day period without toothbrushing.
      Test pastes contained 0.3 per cent Triclosan; seven also contained 0.75 per cent
      zinc citrate; one other contained 2 per cent Gantrez. Plaque and gingivitis
      increased significantly (p < 0.001) between day 0 and day 21 in the control
      group. there was no evidence to reject the assumption of similar efficacy across
      the seven Triclosan/zinc citrate variants. For the combined Triclosan/zinc
      citrate groups, statistically significant reductions in plaque formation and in
      gingivitis relative to the control were recorded. Reductions in plaque and
      gingival bleeding compared to control for the Triclosan/Gantrez group were not
      statistically significant, although reductions in gingival indices were. The
      greater reduction in the Gingival Index of the Triclosan/zinc citrate group was
      also statistically significantly different from that of the Triclosan/Gantrez
      group, suggesting that a dentifrice containing the former would have a greater
      antigingivitis potential than a dentifrice containing the latter.

PMID- 8282426
TI  - The effects of a silica dentifrice containing Triclosan and zinc citrate on
      supragingival plaque and calculus formation and the control of gingivitis.
AB  - A double blind, 7-month parallel clinical study was conducted to determine the
      effect of a dentifrice containing 0.3 per cent Triclosan and 0.75 per cent zinc
      citrate in a 0.8 per cent sodium monofluorophosphate/silica base on supragingival
      plaque, gingivitis and supragingival calculus formation, compared to a 0.8 per
      cent monofluorophosphate/silica control dentifrice. The results of this clinical
      study demonstrate that the use of the Triclosan/zinc citrate dentifrice over a 7
      month period provided a statistically significant and clinically relevant benefit
      in controlling gingivitis, compared to a control dentifrice. Supragingival plaque
      and calculus levels were also significantly reduced in comparison to the effects
      of a control dentifrice.

PMID- 8282427
TI  - The effects of three silica dentifrices containing Triclosan on supragingival
      plaque and calculus formation and on gingivitis.
AB  - A double blind, seven month clinical study was conducted to determine the effects
      of three Triclosan containing test dentifrices on supragingival plaque,
      gingivitis and supragingival calculus formation compared to a 0.8 per cent
      monofluorophosphate-silica control dentifrice. Each test dentifrice contained 0.3
      per cent Triclosan; additionally one contained 0.75 per cent zinc citrate, the
      second contained 2 per cent Gantrez and the third contained 5 per cent
      pyrophosphate. Subjects were assigned to one of the three test groups or to the
      control group according to random allocation within nine strata. Subjects were
      evaluated for supragingival plaque and calculus formation and for gingivitis
      after one, four and seven months' use of the dentifrices. After seven months, the
      Triclosan/Gantrez and the Triclosan/pyrophosphate dentifrices each provided a
      statistically significant reduction of approximately 25 per cent in gingival
      bleeding compared to the control. Neither dentifrice gave statistically
      significant reductions in supragingival plaque or calculus formation. In
      contrast, the Triclosan/zinc citrate dentifrice provided statistically
      significant reductions of 33 per cent in supragingival plaque, 51 per cent in
      gingival bleeding and 67 per cent in supragingival calculus formation. The
      reductions in gingival bleeding and calculus formation were statistically
      superior to those of the Triclosan/Gantrez and the Triclosan/pyrophosphate
      products. The results demonstrate that use of the Triclosan/zinc citrate
      dentifrice over a seven month period provided statistically significant and
      clinically relevant reductions in supragingival plaque and calculus formation,
      and control of gingivitis as compared to a control dentifrice.

PMID- 8282428
TI  - Evaluation of a patient classification system for community health care.
AB  - A patient classification system for community health care developed in the
      Netherlands is described. The system classifies the time nurses devote to the
      care of patients. Its purpose is to support the nurse in managerial work. The
      patient care classification system uses three axes to classify the care: the care
      type, the number of home visits per week and length of service. The patients are
      scored on these three axes after the first visit to the patient. This system
      cannot be used to determine staffing needs on a daily basis but is used as an
      indicator for budgetary and longer term planning purposes. The system was
      evaluated by 65 nurses on 1000 patients during 3 months. It is concluded that the
      care type axis provides good information about the activities that have been
      performed. Another conclusion is that nurses overestimate the number of visits
      per week to the patients.

PMID- 8282429
TI  - Regional cerebral blood flow estimation by neural network-based parametric
      regression analysis.
AB  - An artificial neural network (ANN) model was proposed for real-time estimation of
      regional cerebral blood flow (rCBF), by given head and expired air curves
      obtained through 133Xe inhalation. The network was constructed according to a
      regression model described by a linear differential equation. Experimental
      results compare well with those obtained by conventional curve fitting
      strategies, but the parameter estimation process is much simplified. A systematic
      procedure in developing ANN for parametric regression analysis was introduced;
      networks are constructed according to the selected regression model so that the
      obtained weights of a trained network directly represent parameters of the
      regression model which best fits the observed data set. Such a design-oriented
      methodology extends the classification-based applications of ANN to parametric
      regression analysis, and therefore may have more generalized applications besides
      rCBF estimation.

PMID- 8282430
TI  - A probabilistic rule-based expert system.
AB  - This paper explores a medical expert system combining techniques of Bayesian
      network modelling with ideas of weighted inference rules. The weights of the
      individual rules can be estimated objectively from a training set of actual
      cases; and they can be used in a Monte Carlo stimulation to estimate objectively
      conditional probabilities of diagnosis given particular combinations of symptoms.
      The paper describes and evaluates a medical expert system built according to this
      design. The diagnostic accuracy of the program was found to be similar to that
      obtained through the usual application of Bayes theorem with the assumption of
      conditional independence of symptoms given disease, even though the Bayesian
      classifier has more than 70 times as many numerical parameters. The method may be
      promising in cases where small training sets do not permit accurate estimation of
      large numbers of parameters.

PMID- 8282431
TI  - Parameter sensitivity of a model of viral epidemics simulated with Monte Carlo
      techniques. III. Optimization strategies.
AB  - The output of the sensitivity analysis system, SENSEN, described in the preceding
      two papers is applied to an optimization study for the VESPERS model of the
      spread of infection with influenza virus in a community. We know of no similar
      studies. In this application, constrained, non-linear optimization routines in
      IMSL are used. The optimization study attempts to answer whether behavioural
      modification (modeled as discrete interventions) is necessary to represent
      simultaneously the age-specific attack rates and the epidemic curve. The results
      presented here indicate that such model interventions are necessary.

PMID- 8282432
TI  - Protective effects of silybin and tetrandrine on the outcome of spontaneously
      hypertensive rats subjected to acute coronary artery occlusion.
AB  - The effects of silybin and tetrandrine on the survival of spontaneously
      hypertensive rats subjected to acute coronary artery occlusion were investigated.
      The mortality after acute coronary occlusion in spontaneously hypertensive rats
      (66.7%) was higher than that of control Wistar-Kyoto rats (20%, P < 0.05). Oral
      administration of silybin (300 mg/kg daily) for 8-12 days reduced mortality in
      spontaneously hypertensive rats (0, P < 0.01 in comparison with untreated
      spontaneously hypertensive rats). Administration of tetrandrine 40 mg/kg daily
      for 8-12 days reduced the mortality to some extent (22.2%, P = 0.051, as compared
      with control rats). Silybin reduced blood pressure and the incidence of post
      occlusion arrhythmias in spontaneously hypertensive rats to the same extent as
      tetrandrine. Both silybin and tetrandrine decreased the severity of ventricular
      hypertrophy. Although there were significant decreases in risk zone and infarct
      zone in silybin- and tetrandrine-treated rats, the ratio of infarct to risk zone
      was not changed. The results implies that silybin may be beneficial when used in
      hypertensive patients who develop acute myocardial infarction.

PMID- 8282433
TI  - Effect of zinc deficiency on lipid peroxidation status and infarct size in rat
      hearts.
AB  - The objective of this study was to investigate the effect of dietary zinc on
      endogenous production of lipid peroxides, and on myocardial infarct size in rats.
      Male rats were fed a zinc-deficient diet containing 4 ppm zinc, or a standard
      diet containing 60 ppm zinc. After 3 weeks of diet, half of the animals underwent
      occlusion of the left coronary artery. The remaining animals underwent sham
      operation without occlusion. Forty-eight hours later, the hearts were sampled and
      lipid peroxide levels and infarct size were evaluated. Coronary occlusion was
      associated with an increase in cardiac lipid peroxide levels which were more
      pronounced in the zinc deficient group. However, infarct size appeared to be
      independent from zinc deficiency, despite the free radical-mediated lipid
      peroxide augmentation reported here. The pharmacological limitation of infarct
      size in rats with permanent coronary occlusion is discussed.

PMID- 8282434
TI  - Infundibular pulmonic stenosis with intact ventricular septum: a report of 15
      surgically corrected patients.
AB  - Infundibular pulmonic stenosis with intact ventricular septum of primary origin
      is an uncommon condition. We report 15 such patients (nine males and six females,
      aged 7-36 years) who had undergone surgical correction for the anomaly during the
      period between 1975 and 1992. The occurrence of this clinical setting represents
      0.19% (15/7826) of all cardiac operations and 0.46% (15/3222) of congenital heart
      diseases undergoing surgical correction during that period of time. The lesion
      was of discrete fibromuscular hypertrophy of the infundibulum in all 15 patients.
      The presenting symptoms of most patients were exertional dyspnea and syncope;
      however, five patients with severe obstruction were asymptomatic. The peak
      systolic pressure gradient across the infundibulum ranged from 71 to 230 mmHg.
      There was only one operative death; the remainder had remained well following the
      surgery over a mean follow-up period of 35 months. Surgical correction for
      infundibular pulmonic stenosis is rewarding in the absence of heart failure.

PMID- 8282435
TI  - Impact of early thrombolysis on chest pain score reflecting myocardial ischemia
      in relation to various markers of ischemic damage. TEAHAT Study Group.
AB  - We randomized 352 patients with pain suggestive of acute myocardial infarction
      who were seen less than 3 h after onset of symptoms to either tissue plasminogen
      activator or placebo. The impact of treatment on chest pain score was assessed
      during the first 24 h and related to limitation of final myocardial damage as
      assessed by various indirect markers. The most marked effect of tissue
      plasminogen activator was observed in the chest pain score being reduced by 43%
      in the tissue plasminogen activator group as compared with placebo. Limitation of
      infarct size with tissue plasminogen activator reached the following percentage
      values when various methods were used: maximum serum lactate dehydrogenase I
      activity, 32%; vectorcardiography (QRS vector difference), 20%;
      electrocardiography (Palmeri score), 20%; ejection fraction, 9%. We conclude that
      early thrombolysis in acute myocardial infarction reduces the severity of chest
      pain by nearly 50%. The effect on chest pain is much more marked as compared with
      the effect on various markers of the final ischemic damage.

PMID- 8282436
TI  - Areas of slow conduction in atrial re-entrant tachycardia: a case report and
      review of the literature.
AB  - An electrophysiologic study of atrial tachycardia is presented. During
      tachycardia, transient entrainment and sinus rhythm, two patterns of persistent
      double potentials in the high right atrium and fragmented activity in the low
      atrial septum were observed. No activity was recorded from multiple areas of the
      right atrium with endocardial mapping during sinus rhythm. The observations
      suggest that persistent fragmented activity represents slow conduction within the
      circuit which could be orthodromically entrained. Persistent double potentials
      probably represent slow conduction orthodromically and/or antidromically
      activated outside the circuit. However, a wave front from pacing impulses
      travelling through this area could entrain the circuit.

PMID- 8282437
TI  - Hemodialysis changes the QRS amplitude in the electrocardiogram.
AB  - We studied eight patients to determine whether changes occur in the QRS amplitude
      when these patients are submitted to hemodialysis. The following variables were
      assessed before and after each (N = 28) hemodialysis session: (1) plasma sodium
      and potassium concentrations, (2) QRS amplitude, (3) the heart rate and its
      variability, (4) ventricular volumes, ventricular mass, ejection fraction and
      circumferential fiber shortening, (5) arterial pressure and end systolic stress,
      and (6) body weight. QRS amplitude was computed as the algebraic sum of the
      positive and negative waves of each QRS complex of the electrocardiogram. QRS
      amplitude changes were compared to body weight, ventricular volumes, ventricular
      mass, ejection fraction, circumferential fiber shortening, plasma potassium and
      sodium concentrations, arterial pressure, end systolic stress, heart rate, and R
      R variability. After the hemodialysis sessions we found a significant increase (P
      = 0.0006) in QRS amplitude and a significant decrease in body weight (P =
      0.0001), end diastolic volume (P = 0.043), plasma potassium concentration (P =
      0.000001), end systolic stress (P = 0.025) and systolic arterial pressure (P =
      0.023). Hemodialysis did not produce significant changes in the other variables.
      The statistical analyses performed did not show any significant influence of any
      of the measured variables on the QRS amplitude change. The QRS amplitude
      increases after hemodialysis but the cause of this increase is still unclear.

PMID- 8282438
TI  - Atrial late potentials: paroxysmal supraventricular tachycardia versus paroxysmal
      atrial fibrillation.
AB  - The atrial signal averaged electrocardiogram has been used to detect patients at
      risk for paroxysmal atrial fibrillation but not yet for paroxysmal
      supraventricular tachycardia. The P-wave-triggered signal-averaged
      electrocardiogram, during sinus rhythm, was obtained from 97 subjects divided in
      groups as follows: 30 controls (Group C), 38 patients with documented paroxysmal
      atrial fibrillation (Group A) and 29 with documented paroxysmal supraventricular
      tachycardia (Group B). The atrial duration, root mean square of last 20 and 30 ms
      and the P-QRS segment were measured. Atrial late potentials were considered to
      exist when: atrial duration was > 120 ms and root mean square of last 20 ms were
      < 3.5 microV. The atrial duration (ms) was significantly shorter (P < 0.001) in
      Group C (113.4 +/- 8) than in Group A (138.5 +/- 23.8) and Group B (134.3 +/-
      14.3). The root mean square (microV) of last 20 ms was significantly higher (P <
      0.001) in Group C (5.2 +/- 2.5) than in Group A (2.5 +/- 1.3) and Group B (3.1 +/
      1.8). Atrial late potentials were present in 3/30 controls, 32/38 of Group A
      cases and 23/29 of Group B. The specificity and sensitivity were, respectively:
      0.90, 0.84, for Group A, and 0.90, 0.79 for Group B. The P-QRS segment (ms) was
      significantly shorter (P < 0.01) in Group B (12.5 +/- 9.4) than in Group C (32.5
      +/- 16.9) and Group A (20.5 +/- 13.4).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282439
TI  - Catheter ablation of the atrioventricular junction by radiofrequency energy
      delivered across the interventricular septum using a left sided approach.
AB  - We describe seven successful cases of ablation of the atrioventricular (AV)
      junction by passing radiofrequency (RF) energy between the tip of an electrode on
      the left ventricular aspect of the interventricular septum and a further
      electrode on the right side of the His bundle. All had undergone unsuccessful
      attempts at conventional unipolar RF ablation from the right and left side of the
      heart.

PMID- 8282440
TI  - Dilated cardiomyopathy and myocarditis in Kenya: an endomyocardial biopsy study.
AB  - We have studied, by light and electron microscopy, left ventricular
      endomyocardial biopsy specimens from 18 African patients (14 men) with idiopathic
      dilated cardiomyopathy in Nairobi. Nine patients (50%) had evidence of healing
      myocarditis, that is the presence of a mild inflammatory cell infiltration within
      the myocardium. Interstitial fibrosis was prominent in five patients (28%) and in
      all 18 specimens there were hypertrophied muscle fibres. Therefore, half of the
      patients with idiopathic dilated cardiomyopathy had histological signs of a
      previous myocarditis. There was no serological evidence of a previous or recent
      coxsackie infection or any other common viral infections. It seems probable that
      the myocarditis was due to an inappropriate immunological reaction to myocardial
      muscle.

PMID- 8282441
TI  - Myocardial infarction due to coronary artery compression by aortic root abscess.
AB  - A 44-year-old man with aortic valve disease presented with myocardial ischaemia
      and ultimately infarction in the presence of suspected endocarditis. Thoracic
      computerised tomographic scan and coronary arteriography suggested the ischaemia
      was caused by external compression of the left coronary artery due to an aortic
      root abscess, later confirmed at surgery. Myocardial ischaemia is an infrequent
      accompaniment of infective endocarditis and is most commonly due to coexisting
      coronary disease. More rarely, emboli from vegetations may give rise to
      infarction. Although aortic root abscess is a well recognised complication of
      aortic valve endocarditis, coronary artery compression is an unusual mode of
      presentation and we believe this to be the first reported case of myocardial
      infarction resulting from external compression in this setting.

PMID- 8282442
TI  - Coronary vasospasm, multiple coronary thrombosis, unstable angina and essential
      thrombocytosis.
AB  - Rarely, essential thrombocythemia has led to coronary artery occlusion. Only one
      patient has been described, in whom coronary angiography demonstrated multiple
      coronary thrombosis. We report a case of coronary vasospasm, multiple coronary
      thrombosis involving right and left coronary artery and possibly leading to
      myocardial infarction and unstable angina pectoris in a woman with migraine,
      Raynaud's phenomenon, and essential thrombocytosis.

PMID- 8282443
TI  - Double orifice in prolapsing mitral valve.
AB  - A prolapsing mitral valve with a double orifice ('hole type') was documented by
      echocardiography in a 35-year-old male. His symptoms were associated to
      supraventricular ectopic beats and persisted unchanged during a 3-year follow-up.
      This malformation is usually considered benign but, as fragmentation of the
      atrioventricular conduction tissue was reported in some cases, a periodic
      observation is advisable.

PMID- 8282444
TI  - Detection of intra-atrial conduit leakage by transesophageal echocardiography.
AB  - A 19-year-old male patient who had undergone total cavo-pulmonary connection for
      complex congenital cyanotic heart disease with partial anomalous pulmonary venous
      return, was found to have persistent postoperative cyanosis. Transesophageal
      echocardiography disclosed leakage of the intra-atrial Gortex conduit with a
      right-to-left shunt. Prompt re-do operation confirmed the site of the leakage
      which was successfully repaired. Intraoperative transesophageal echocardiography
      may be indicated so as to avoid a secondary open-chest procedure for this
      complication.

PMID- 8282445
TI  - Imaging of cardiac metastatic melanoma: trans-oesophageal echocardiography or
      magnetic resonance imaging?
AB  - Two cases of isolated cardiac metastatic melanoma are described. Images from the
      first case using magnetic resonance scanning were complimented by the clearer
      images obtained with trans-oesophageal echocardiography in the second case. Trans
      oesophageal echocardiography may be the technique of choice to image intra
      cardiac metastatic tumours.

PMID- 8282446
TI  - Sarcoid, amyloid and heart failure.
AB  - We report the case of an adult West Indian patient who presented with heart
      failure 20 years after an initial diagnosis of pulmonary sarcoidosis.
      Endomyocardial biopsy revealed AL type amyloid which was later found to be
      secondary to an underlying multiple myeloma.

PMID- 8282447
TI  - Thrombolysis in unstable angina.

PMID- 8282448
TI  - The law, social control, and drug policy: models, factors, and processes.
AB  - The law is governmental social control; it is the state's most direct
      intervention in the normative life of its citizens. Psychoactive drugs are
      controlled through regulation and prohibition, depending on the legal status of
      the particular substance. Licit drugs are made available through a regulatory
      scheme of medical prescription and legal sale; health is protected through
      investigating, licensing, and monitoring the quality and quantity of drugs and
      the circumstances in which they are consumed. Illicit drugs are forbidden by
      criminal statutes which create offenses related to both use (i.e., possession)
      and distribution (i.e., trafficking, importing); no level of use is acceptable
      and there is no legal source of supply. The agents of control for licit drugs are
      physicians, scientists, and health bureaucrats. In contrast, the agents that
      enforce illicit drug laws are the police, prosecutors, courts, and customs
      officials. The general preventive effect of the criminal law is activated through
      the threat of punishment and the setting of educative and moral standards of
      permitted behavior. The acceptability of drug-use behavior has varied widely
      across time, culture, and substance. What have we learned about the legal control
      of psychoactive substances? It is evident that a state may become increasingly
      overdependent on the law and neglect other alternatives of social control that
      may sometimes be more effective or less costly in reducing the possible harmful
      effects of drug use. The law is a powerful but also blunt instrument of social
      control.

PMID- 8282449
TI  - Prevention of substance use problems: models, factors, and processes.
AB  - The use of substances for medical or nonmedical reasons occurs in most cultures.
      Regardless of the reason for use, however, most types of substance use (or drug
      taking behaviors) have their associated problem states. The prevention of
      substance use problems is an important issue and need in every society. In this
      review we present and discuss various models and factors that purport to describe
      and predict patterns of drug use, and we discuss various strategies to prevent
      the occurrence of substance use problems.

PMID- 8282450
TI  - Approaches to ethnicity: clearing roadblocks in the study of ethnicity and
      substance use.
AB  - This paper reviews a number of indicators of ethnicity commonly used in
      alcohol/drug use studies. These include the racial, natal, symbolic and cultural
      approaches to ethnicity. The utility and limitations of each of these approaches
      is scrutinized. Because ethnicity is a multidimensional concept, using only one
      dimension, as is the case in many alcohol/drug use studies, is inadequate. One of
      the major weaknesses of studies of ethnicity and substance use is the failure to
      recognize the presence of subcultural differences within an ethnic group.
      Implications of the present review for future research in ethnicity and substance
      use/misuse and for future development of culturally sensitive programs and
      services are discussed.

PMID- 8282451
TI  - Beverage alcohol as a constraint to development in the Third World.
AB  - The patterns of production and consumption of beverage alcohol throughout the
      Third World pose a constraint to economic and social development. A
      multidisciplinary academic literature has arisen in response to this phenomenon.
      It has done so over two rather distinct time periods. The first began to take
      shape during the 1970s and continued through the mid to late 1980s. It gave rise
      to a set of three rather discrete foci: 1) on developing theoretical frameworks
      across academic disciplines, 2) on identifying beverage alcohol's development
      impact, and 3) on the generating and implementing of alcohol policies. Since the
      1980s the literature has maintained those foci, but contributions to the
      literature did a more complete job of integrating them into more complete (and
      less discrete) treatments.

PMID- 8282452
TI  - Observations on the recent history of drug user counseling.
AB  - The drug user counselor role is explored in terms of its changing nature over the
      course of the past 25 years. Initially, the drug user counselor could be
      characterized as a professional based on his or her experience, or as an ex
      addict paraprofessional in the language of that time. Working very largely with a
      heroin-using clientele, the counselor was the advisor and role model who could
      not be conned and, thereby, the essential counterpart to the mental health
      professionals who were entering the drug misuse field. Over time, these latter
      professionals based on education have become increasingly evident and the
      "professionals of experience" have become less so in accord with changes in the
      demography, drug-using characteristics, and psychological functioning of drug
      user clients. Nonetheless, studies that support the particular efficacy of
      counselors of education for all but drug user clients with significant
      psychopathology are lacking. Moreover, aspects of therapeutic interaction that
      are more largely engaged in by "professionals of experience" are threatened by
      the diminution in that group's numbers and the credentialing out of
      nontraditional job functions. Over the past few years, awareness of the
      significance of the contributions of "professionals of experience" has been
      reawakened by the threat of AIDS and the recognition of counselors' contributions
      to outreach and AIDS prevention counseling.

PMID- 8282453
TI  - Serum beta-carotene and antioxidant micronutrients in children with cancer. The
      'Cancer in Children and Antioxidant Micronutrients' French Study Group.
AB  - Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene,
      zinc and selenium for 418 children with newly diagnosed malignancy were compared
      with those of 632 cancer-free controls. Incident cancer cases and controls were 1
      16 years old and recruited in 1986-1989. Age- and sex-adjusted serum
      concentrations of retinol, beta-carotene and alpha-tocopherol were significantly
      inversely associated with cancer. In similar models, the odds ratio (OR)
      comparing the highest with the lowest quintile was 2.06 (95% confidence interval
      [CI] 1.40-3.02) for retinol, 3.87 (95% CI: 2.54-5.90) for beta-carotene, 2.15
      (95% CI: 1.48-3.10) for alpha-tocopherol, 1.29 (95% CI: 0.75-2.23) for selenium,
      and 1.94 (95% CI: 1.17-2.23) for zinc. The cancer sites that were associated with
      serum beta-carotene were, in general, leukaemia, lymphoma, central nervous
      system, bone and renal tumours. Moreover, leukaemia was associated with low mean
      serum levels of retinol, selenium and zinc. Subjects with lymphoma, bone and
      renal tumours also had lower mean retinol and alpha-tocopherol levels than
      controls. Brain tumour patients had low vitamin E levels. Low serum values of
      antioxidant vitamins were associated with childhood neoplasm occurrence. Some
      site-specific effect was reported. Low peripheral nutrient levels are not
      considered as cancer promoters but rather as an impairment of the body's defence
      mechanism occurring during the cancer-related metabolic and nutritional
      disturbances and inflammation processes.

PMID- 8282454
TI  - HDL-cholesterol and breast cancer: a joint study in northern Italy and southern
      France.
AB  - The goal of the present study is to evaluate HDL-cholesterol (HDL-C) as a marker
      of breast cancer (BC) risk. It is based on several epidemiological and biological
      studies and is justified by the rising incidence of breast cancer throughout the
      world. A hospital-based study on host-related risk factors and breast cancer,
      conducted with similar methods in northern Italy and southern France, provided
      the biological data, the information on the established BC risk factors and on
      nutrition for 307 cases and 329 controls. This data set allowed for a thorough
      analysis of the relationship of HDL-C with established risk factors for BC and
      also of its association with BC at the time of diagnosis. Most of our findings on
      HDL-C determinants in the control sample are comparable to previous studies. The
      BC risk factors associated with reproductive life correlate with HDL-C levels:
      the protective factors are associated with a lower level of HDL-C and inversely.
      The same is true for nutritional factors such as alcohol. For these determinants,
      the trend is similar for cases and controls, and HDL-C level appears to be
      related to oestrogen metabolism. Thus it may be considered as a marker of BC
      risk. Our results indicate that high HDL-C levels should be especially checked in
      women aged > or = 60 years, or in premenopausal women presenting a low BMI, or in
      postmenopausal women with an early menopause.

PMID- 8282455
TI  - Oestrogen replacement therapy and breast cancer risk: a case-control study.
AB  - The relationship between oestrogen replacement therapy and breast cancer risk was
      examined based on data obtained from a population-based case-control study of
      breast cancer on Long Island, New York, USA. Cases were defined as female
      residents of two Long Island counties, aged 20-79, who were diagnosed with breast
      cancer between 1 January 1984 and 31 December 1986. Age- and county-matched
      controls were selected from driver's licence files. Among all postmenopausal
      women, there was no significant association between ever-use of hormones to treat
      menopausal symptoms and breast cancer risk. There was also no significant
      positive association in any subgroup defined by type of menopause (natural,
      hysterectomy with at least one ovary intact, bilateral oophorectomy) or age at
      menopause. Additionally, there was no increasing trend in risk with duration of
      use either overall or in any subgroup, nor was there an effect at any interval
      since last use. A significant elevation in risk was observed in women with 10-19
      years since first exposure, which was concentrated in women with a natural
      menopause or hysterectomy with at least one ovary remaining, and women aged > 45
      at menopause. Results of logistic regression analysis revealed no important
      confounding by any of several established breast cancer risk factors. However, a
      significant interaction was observed between body mass index (BMI) and oestrogen
      use, with an effect of oestrogen use being seen only in the thinnest tercile.
      Although biologically plausible explanations for this finding exist, the effect
      of chance cannot be ruled out.

PMID- 8282456
TI  - Salt and gastric cancer: a case-control study in Puerto Rico.
AB  - A total of 136 incident intestinal type gastric cancer cases and 151 age
      comparable population controls were interviewed in Puerto Rico about their
      dietary habits with special emphasis on dietary salt consumption. All interviews
      were conducted at home using a quantitative dietary frequency instrument. The
      weekly intake of foods was estimated from the reported frequency of consumption
      and portion size according to a food model. The dietary salt exposure was
      estimated from the intake of nine selected food items which are highly salted
      food items commonly consumed in Puerto Rico. A strong (odds ratio [OR] = 3.34)
      and statistically significant (P < 0.001) unadjusted difference was found between
      cases and controls regarding dietary salt exposure. A statistically significant
      dose response for the index of salt exposure and gastric cancer was also found.
      The association remained positive and statistically significant after
      simultaneously adjusting for the confounding effects of sex, education and
      cigarette smoking.

PMID- 8282457
TI  - The role of sexual factors in the aetiology of cervical dysplasia.
AB  - The effect of sexual behavior on the risk for cervical dysplasia was evaluated in
      a case-control study. Cases (n = 257) had a histologically confirmed diagnosis of
      cervical dysplasia. Controls (n = 705) were sampled from the general population.
      A postal questionnaire was used to obtain information about, among other things,
      age at first sexual intercourse, number of sexual partners, current frequency of
      intercourse and contraceptive use. Information was also collected about other
      risk factors for cervical dysplasia, in order to adjust for possible confounding.
      We observed higher risks for cervical dysplasia (mild, moderate and severe) with
      increasing number of sexual partners. This effect appeared to be dependent on
      smoking behaviour. For women who reported more than six sexual partners, the
      adjusted odds ratio (aOR) was 9.1 (95% CI: 3.5-23.7) for non-smokers, and 26.4
      (95% CI: 11.8-58.8) for women who smoked > or = 20 cigarettes per day. The
      effects of age at first sexual intercourse and current frequency of intercourse
      disappeared after adjustment for other risk factors. Use of oral contraceptives
      for > 10 years increased the risk (aOR = 2.3; 95% CI: 1.2-4.6). Thus, the number
      of sexual partners, especially in combination with smoking behaviour, appeared to
      be the most important risk factor for cervical dysplasia.

PMID- 8282458
TI  - Reliability of passive smoke exposure histories in a case-control study of lung
      cancer.
AB  - Despite the growing number of studies on the health effects of passive smoke
      exposure, few data exist on the quality of questionnaire data on passive smoking.
      To measure the reliability of passive smoking histories, re-interviews were
      conducted for 110 subjects (37 cases and 73 controls) as part of a larger study
      of lung cancer among non-smoking women in Missouri. Agreement was high both for
      parental smoking status (94% concordance; kappa = 0.82) and for spousal smoking
      status (84% concordance; kappa = 0.67). Concordance also was relatively high for
      cigarette pack-years of exposure due to the parents or spouse. Reliability tended
      to be somewhat higher among controls than among cases, and for exposure due to a
      parent or spouse than for that due to other household members. Questions on the
      perceived harmfulness of passive smoke exposure showed no differences between
      cases and controls. These findings indicate a high degree of repeatability in
      responses regarding passive smoking, but also suggest the potential for
      misclassification of passive smoke exposure status, the desirability of
      standardized questions on passive smoking, and the need for additional studies of
      reliability and validity.

PMID- 8282459
TI  - Passive smoking and chronic respiratory disease symptoms in non-smoking adults.
AB  - A prospective study was conducted to investigate the possible effects of
      environmental tobacco smoke (ETS) on the development of definite symptoms of
      airway obstructive disease (AOD) in a non-smoking adult population. In all 3914
      subjects completed a standardized respiratory symptoms questionnaire in 1977 and
      1987 and a computerized algorithm was used to identify new cases of definite
      symptoms of AOD during the follow-up period. In multivariate logistic regression
      models which adjusted for age, gender, income, educational level, years smoked in
      the past, and concentrations of ambient air pollutants, ETS exposure during
      childhood only was associated with a relative risk (RR) of 1.09 (95% confidence
      interval [CI]: 0.69-1.79), during adulthood only with an RR of 1.28 (95% CI: 0.90
      1.79), and during both childhood and adult life with an RR of 1.72 (95% CI: 1.31
      2.23). Results were not significantly changed when only lifetime never-smokers
      were used in analyses, and no interaction between ETS exposure and concentrations
      of ambient air pollutants was observed.

PMID- 8282460
TI  - Children's exposure to parental smoking in West Germany.
AB  - In this study, we derive national estimates of the prevalence of children's
      exposure to parental smoking in West Germany. The estimates are based on a
      national health survey conducted in 1987 and refer to those parents living in the
      same household as the child. Estimated prevalences of maternal smoking range from
      18.9% among children aged < 2 years to more than 30% among 2-5 and 6-13 year old
      children. Estimates of paternal smoking prevalence are considerably higher: 33.7%
      among children < 2 years old and 43.1% and 46.8% among 2-5 and 6-13 year old
      children, respectively. The prevalence of at least one smoking household member
      was 49.9% among 2-5 year old children, while a clear majority of children aged <
      2 years (58.8%) and 6-13 (67.5%) were living in a household with at least one
      smoker. For all age groups, prevalence of maternal and paternal smoking was
      considerably higher among children of less-educated parents than among children
      of better-educated parents. Given the high prevalence of parental smoking and the
      association of parental smoking with a variety of respiratory diseases in
      children, a large proportion of these diseases could be prevented by efforts to
      reduce smoking among parents.

PMID- 8282461
TI  - Comparison of a food frequency questionnaire with a 10-day weighed record in
      cigarette smokers.
AB  - The aim of the study was to compare nutrient intakes estimated by a self
      administered food frequency questionnaire and a 10-day weighed record in 122 men
      and 179 women cigarette smokers aged 40-59 years. Comparison of nutrient intake
      by means, per cent mean differences and ability to rank individuals correctly
      between the methods showed good agreement for most nutrients. Spearman rank
      correlations were statistically significant for all nutrients except vitamin A
      intake in men; adjusting for energy intake increased the strength of the
      associations found. Bland-Altman plots showed differences in agreement over the
      range of intakes for energy in men and ascorbic acid in women. Food frequency
      questionnaires may be used to assess the dietary habits of smokers, but some
      caution is required and the method should be assessed in the study sample before
      being applied to the whole sample.

PMID- 8282462
TI  - Mortality and morbidity among blue and white collar workers in the Honolulu Heart
      Program cohort.
AB  - There has been a controversy regarding occupation, as defined by blue and white
      collar work, and coronary heart disease (CHD). In a large long-term prospective
      study of the Honolulu Heart Program cohort, there were no significant differences
      between these two occupational classifications and the incidence rates of fatal
      and non-fatal CHD. Nor were there significant differences in total mortality,
      stroke or total cancer although there were very small but significant differences
      in some CHD risk factors. Unlike the previous studies, this investigation was
      free of prevalent cases of CHD at baseline and controlled for the major risk
      factors of CHD. We question the utility of using this occupational classification
      to investigate the causes of CHD.

PMID- 8282463
TI  - The prevalence of dementia, depression and neurosis in later life: the Liverpool
      MRC-ALPHA Study.
AB  - Prevalence rates for psychiatric disorders in the elderly are presented from the
      initial cross-sectional stage of a longitudinal community study of the incidence
      of dementia in the city of Liverpool. Together with five other centres in the UK
      the MRC-ALPHA project forms part of the MRC multicentre incidence study of
      dementia and cognitive decline. An age- and sex-stratified random sample of 5222
      subjects aged > or = 65 was interviewed at home using the Geriatric Mental State
      AGECAT package to provide computer diagnoses. The overall age-standardized
      prevalence rates for organic disorder (4.7%) depressive illness (10.0%) and the
      neuroses (2.5%) are consistent with levels found in previous smaller studies that
      have used GMS-AGECAT. Each of these diagnoses is more common in females than
      males. A rise in organic disorder with age is confirmed as continuing into the
      oldest age groups for both sexes. An apparent decline with age observed for
      depression and neurosis diagnoses disappears when organic cases are excluded from
      the analysis.

PMID- 8282464
TI  - The relationship between dyspnoea and main lifetime occupation in the elderly.
AB  - PAQUID is a prospective epidemiological study of mental and functional ageing.
      Based on the data collected during the baseline screening of this cohort, the
      present paper will examine the relationship between main lifetime occupation and
      the presence of dyspnoea in a representative sample of 3777 subjects aged > or =
      65 years; living at home in the south-west of France. Subjects were considered
      dyspnoeic if they had a dyspnoea level 3, 4 or 5 according to the Fletcher
      classification. Occupational categories were determined according to the
      classification of the French 'Institut National de la Statistique et des Etudes
      Economiques,' and to the type of occupation for blue-collar workers. The
      proportion of dyspnoeic subjects varied significantly according to the
      occupational categories (from 13% for teachers to 37% for farm workers) and to
      the type of work (from 18% for printing workers to 41% for building workers).
      When age, sex, weight, smoking history, place of residence, educational level and
      some concurrent diseases were adjusted for, former farm workers (odds ratio [OR]
      = 3.3, 95% confidence interval [CI]: 2.0-5.6), farm managers (OR = 2.1, 95% CI:
      1.3-3.5), domestic service employees (OR = 1.9, 95% CI: 1.2-3.6) and blue-collar
      workers (OR = 1.9, 95% CI: 1.3-3.0), had a higher risk of dyspnoea than subjects
      who used to have an intellectual occupation. The risk was not significant for
      other professional categories. These results demonstrate the important long-term
      effect of previous professional activities on respiratory health in the elderly.

PMID- 8282465
TI  - Food sources of nutrients in the diet of elderly Italians: I. Macronutrients and
      lipids.
AB  - The major sources of macronutrients in the Italian diet were assessed. Elderly
      Italians, aged > or = 60 recorded their weighed intake for a 7-day period. A
      total of 945 subjects from 14 centres throughout Italy participated during the
      period 1983-1987. These data were used to quantify the contribution of individual
      foods to the total intake of and variability in intake of kilocalories, protein,
      carbohydrate, total fat, saturated fat, oleic acid, polyunsaturated fatty acids,
      linoleic acid, and cholesterol. The foods ranked one to five for Italy were
      compared to the top five foods contributing to these nutrients in the diet of the
      elderly in the US based on the NHANES II Survey (1976-1980). These data provide
      information for the design of an Italian data-based quantitative food frequency
      questionnaire. They are also of interest in their description of an
      industrialized, well-nourished population with a dietary pattern markedly
      different from the US--lower in saturated fat, higher in complex carbohydrate and
      higher in alcohol.

PMID- 8282466
TI  - Food sources of nutrients of the diet of elderly Italians: II. Micronutrients.
AB  - The foods which contribute most to the intake of selected vitamins and minerals
      were evaluated for the elderly in Italy and compared to food sources of nutrients
      in the US. A sample of 945 Italians, aged > or = 60, from 14 centres throughout
      Italy, each completed weighed 7-day food records during the period 1983-1987.
      These data were used to quantify the contribution of individual foods to the
      total intake of and variability in intake of vitamin A, thiamin, riboflavin,
      vitamin C, calcium, and iron. In addition, those foods contributing most to
      micronutrient intake for the Italians were compared to those foods contributing
      most for the elderly in the US as recorded by the NHANES II Survey (1976-1980).
      Overall, there was a preponderance of vegetable rather than animal sources, and
      of less processed food sources in Italy. In Italy, wine was an important source
      of several nutrients, including iron and riboflavin. These data are useful for
      characterizing diet in a well-nourished population with marked differences in
      diet from the US. They may also form the basis for a quantitative food frequency
      questionnaire for epidemiological studies in Italy.

PMID- 8282467
TI  - Occupational physical activity and the occurrence of spontaneous abortion.
AB  - The influence of occupational physical activity on early pregnancy failure was
      examined in a population of 24 cleaners, 36 kitchen staff and 110 clerical
      workers from 39 Dutch hospitals who were enrolled before becoming pregnant
      between August 1987 and January 1989. The occupational energy expenditure was
      defined by an intensity and a fatigue score, which were studied alone and in
      combination with working hours and working speed. The occupational biomechanic
      load was defined by a peak and a chronic pressure score. The intensity and the
      fatigue score of the work, whether or not in combination with working hours and
      working speed, were not related to the occurrence of spontaneous abortion. Work
      involving a high biomechanic load, in particular high peak pressure scores,
      showed an odds ratio (OR) for spontaneous abortion of 3.1 (95% confidence
      interval [CI]: 1.1-8.9). There were strong indications that work involving
      bending (OR = 3.2; 95% CI: 1.3-9.8) rather than lifting (OR = 1.1; 95% CI: 0.3
      3.4) was the main cause.

PMID- 8282468
TI  - Breastfeeding and the risk of sudden infant death syndrome.
AB  - The New Zealand Cot Death Study, a multicentre case-control study, was set up to
      identify risk factors associated with sudden infant death syndrome (SIDS). In the
      3 years of the study there were 485 infant deaths classified as SIDS in the study
      areas and 1800 infants who were randomly selected as controls. Data were
      collected by parent interviews and from obstetric notes. A full set of data for
      this analysis was available from 356 cases and 1529 control infants. The
      relationship between length of any breastfeeding and SIDS was examined: 92% of
      the controls were initially breastfed compared to 86% of the cases. As time went
      by, cases stopped breastfeeding sooner than controls: by 13 weeks, 67% controls
      were breastfed versus 49% cases. A reduced risk for SIDS in breastfed infants
      persisted during the first 6 months after controlling for confounding
      demographic, maternal and infant factors. Infants exclusively breastfed 'at
      discharge from the obstetric hospital' (odds ratio [OR] = 0.52, 95% confidence
      interval (CI): 0.35-0.71) and during the last 2 days (OR = 0.65, 95% CI: 0.46
      0.91) had a significantly lower risk of SIDS than infants not breastfed after
      controlling for potential confounders. We have shown a substantial association of
      breastfeeding with a lowered risk for SIDS. This supports the need for more
      positive promotion and active community support to further enhance the level and
      length of exclusive breastfeeding.

PMID- 8282469
TI  - The effects of lead levels on the growth of word recognition in middle childhood.
AB  - The relationship between dentine lead levels and the development of word
      recognition abilities from 8 to 12 years of age was studied in a sample of 636
      children drawn from a birth cohort of 1265 New Zealand children. Data were
      analysed by growth curve modelling methods to characterize the relationship
      between early lead levels and subsequent development of word recognition
      abilities. The results of this analysis showed: i) Before adjustment for
      confounding and other factors children who had lead levels of > or V 8 p.p.m. had
      mean test scores which were consistently 5 points lower than children with levels
      of 0-3 p.p.m. There was no evidence to suggest either catch-up or deterioration
      in the performance of those with levels of > or = 8 p.p.m. ii) After adjustment
      for both confounding covariates and potential sample selection bias these
      differences reduced to about 3 points between those with levels of > or = 8
      p.p.m. and those with levels of 0-3 p.p.m. These differences, however, remained
      statistically significant (P < 0.05) or marginally significant (P < 0.10). It was
      estimated that the 3-point difference in word recognition skills amounted to
      approximately 4-6 months' delay in the word recognition abilities of those with
      mildly elevated lead levels. The results of this study are generally consistent
      with the view that early exposure to lead results in very small, statistically
      detectable but apparently enduring deficits in cognitive abilities.

PMID- 8282470
TI  - Birthplace as a risk factor in motor neurone disease and Parkinson's disease.
AB  - A proportional mortality study was conducted to determine if state of birth is a
      risk factor associated with motor neurone disease (MND) and Parkinson's disease
      (PD) using US death certificate information for 1981. State of birth was used as
      a surrogate variable for location of early childhood environment. A gradient of
      risk by geographical area in the US was found for MND and PD. Cerebral vascular
      accident (CVA) deaths served as a comparison group. Multiple sclerosis (MS)
      deaths were analysed to validate the methods used. A geographical relationship
      between latitude proportional mortality ratios for MND, PD and MS by state of
      birth, and a geographical relationship between latitude and proportional
      mortality ratios for MND and MS by state of birth were found. Statistical
      modelling was used to compare the deaths from MND, PD, MS, CVA to all other
      deaths in the US by state of birth. The resulting models were evaluated to
      determine if any individual states were not well represented by the model for
      each disease. As predicted, no pattern was evident for CVA. The geographical
      gradient observed for MS was as predicted by other studies. The geographical
      pattern found for MND has a northwest to southeast gradient and the pattern found
      for PD has a west to east gradient.

PMID- 8282471
TI  - Injury severity scoring and length of stay in hospital of war casualties-
      demonstration of an association and possible selection bias.
AB  - The Injury Severity Score (ISS) is a widely used measure of anatomical injury. It
      is the sum of squares of the highest scores on the Abbreviated Injury Scale (AIS)
      in each of the three most severely injured body regions. This study was designed
      to describe the relationship between ISS and length of stay (LOS) in hospital.
      The ISS was independently determined by four physicians who studied 491 war
      casualties, excluding dead on arrival and non-trauma patients. The study
      demonstrates non-linear and non-homogeneous relationships between ISS and LOS.
      Exclusion of fatalities resulted in biased (higher) estimates of LOS among those
      with ISS scores of 25-66. The patients could be grouped into five categories
      according to their maximal AIS (MAIS): (1) Slight injury--i.e. those with
      injuries appropriate for AIS scores 1 or 2 that lead to an LOS of median 5 days;
      (2) Moderate injury--i.e. those with injuries appropriate to AIS scores of 3,
      with an expected median LOS of 10 days; (3) Severe injuries--i.e. those with
      injuries appropriate to AIS scores of 4, with expected median LOS of about 17
      days; (4) Very severe injuries--i.e. those with one injury appropriate to an AIS
      score of 5; and (5) Multiple severe injuries--those who are severely wounded in
      two or more body regions, i.e. those with two or more injuries appropriate to AIS
      scores of 5 and 4, with a median LOS of 39 days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282472
TI  - Epidemiology of acute wrist trauma.
AB  - Epidemiological data on wrist injuries in a population can be used for planning
      by applying them to criteria for care and thus deriving estimates of provisions
      for care according to currently desirable standards. In a 1-year study all
      patients > or = 15 years with acute wrist trauma and treated in the emergency
      room were examined according to an algorithm until a diagnosis was established.
      The overall incidence of wrist trauma was 69 per 10,000 inhabitants per year.
      Incidence of wrist trauma requiring x-ray examination was 58 per 10,000 per year.
      The incidence of distal radius fractures was 27 per 10,000 per year (males, 16
      per 10,000, females, 37 per 10,000 per year). In order to evaluate the
      completeness (defined as the proportion of patients with wrist injuries seen in
      the emergency room to all patients with wrist injuries in the catchment area) of
      the hospital-based data an analysis was performed using data from a population
      based study. A completeness rate of 0.56 (95% confidence interval: 0.31-0.78) was
      found. An x-ray had been taken for all patients reporting a fracture thus
      justifying the use of fractures as an incidence measure when comparing groups of
      patients with wrist trauma.

PMID- 8282473
TI  - A community-based randomized trial of home-made oral rehydration therapies.
AB  - A field trial of the relative efficacy of three oral rehydration therapies (ORT)
      in the treatment of acute childhood diarrhoea in children < 5 years old was
      carried out in a rural Ethiopian district. The three ORT were 1) pre-packaged
      glucose and salt solution (GORS; n = 153), 2) home-made cereal added to pre
      packaged salt solution (CBORS; n = 154), and 3) entirely home-made cereal-based
      and salt therapy (CBORT; n = 156). Out of 127 eligible peasant associations, 18
      were randomly selected, and groups of six were then randomly assigned to receive
      one of the three treatment options. In infants aged 0-12 months, after adjusting
      for baseline weight and diarrhoea frequency, CBORT was found to be superior (P <
      0.01) to GORS and CBORS in terms of weight gain at 24, 48, and 96 hours. There
      were no significant between-group differences in weight gain in children > 12
      months old. Over the 96-hour duration of follow-up, mothers' compliance was
      significantly better among those giving CBORT when compared to CBORS (P < 0.001)
      or GORS (P < 0.013). The results of this field trial indicate that CBORT is an
      efficacious alternative to GORS or CBORS in the treatment of acute childhood
      diarrhoea in rural community settings. Larger scale, effectiveness studies are
      recommended.

PMID- 8282474
TI  - Hepatitis B virus infection among pregnant women in northeastern Romania.
AB  - We conducted a serological survey of pregnant women attending prenatal clinics in
      northeastern Romania to determine the prevalence of hepatitis B virus (HBV)
      infection in this population. Overall, 162 (28%) of 573 women had evidence of
      past or current HBV infection, and 48 (8.4%) were carriers. The prevalence of
      past or current infection rose with age, but did not differ by educational level,
      occupation, or rural versus urban residence. Integration of hepatitis B vaccine
      into routine childhood immunization schedules, with the first dose given at
      birth, may have a substantial impact on HBV infection in Romania by preventing
      both perinatal and early childhood transmission.

PMID- 8282475
TI  - Control of neonatal tetanus in southern Thailand.
AB  - Prior to 1989, Krabi and Satun, two neighbouring provinces with similar
      socioeconomic background and health service coverage, had the highest reported
      incidence rates of neonatal tetanus in Thailand (3 per 1000 livebirths). A
      control programme was conducted between 1989 and 1991. The objective of this
      study was to examine changes in prevalence of risk factors among the population
      and changes in incidence rates of this disease due to this programme. Two 30
      cluster surveys to measure prevalence rates of risk factors were conducted in
      Krabi, before and after the campaign. Information on incidence was obtained from
      routine surveillance. The intervention in Krabi consisted of mass immunization
      and intensive education for traditional birth attendants (TBA) whereas only the
      latter was carried out in Satun. The incidence of neonatal tetanus in both
      provinces declined dramatically to less than 0.4 per 1000 livebirths in 1990 and
      1991. From 1989 to 1991, in Krabi Province, the coverage of at least two doses of
      tetanus toxoid injections at any time prior to delivery, delivery by trained
      health personnel, acceptable sterile technique for umbilical cord cutting and
      correct method of dressing the umbilical stump rose from 70 to 88%, 55-80% cent,
      80-94% and 40-74%, respectively. Reduction in the incidence rate of neonatal
      tetanus was achieved by strengthening of routine health services with or without
      additional mass immunization. Considering that the coverage of immunization has
      not yet been completed and the prevalence rates of different risk factors are
      still high, further attempts to improve the problem of neonatal tetanus are
      necessary.

PMID- 8282476
TI  - Paralytic poliomyelitis in Oman: association between regional differences in
      attack rate and variations in antibody responses to oral poliovirus vaccine.
AB  - Variation in attack rates of paralytic disease by region during the 1988-1989
      epidemic of type 1 poliomyelitis in Oman provided the stimulus to test the
      hypothesis that these observations were due to regional differences in the
      response of infants to trivalent oral poliovirus vaccine (OPV). Seroprevalence
      studies of 394 children born during the outbreak were conducted in six different
      regions of Oman and in two socioeconomic status (SES) groups in the capital city
      of Muscat; a seroconversion study was also carried out in 105 infants born after
      the outbreak. Seroprevalence rates by region after receipt of at least three
      doses of OPV ranged from 90% to 100% (median 94%) to poliovirus type 1, and from
      86% to 100% (median 97%) to type 2, and from 47% to 79% (median 72%) to type 3,
      with the lowest rates observed in regions with the highest incidence of type 1
      paralytic disease. In Muscat, seroprevalence rates were also significantly lower
      in low versus high SES groups (type 1: 84% versus 98%, respectively [P = 0.006];
      type 3: 59% versus 86%, respectively [P = 0.001]). In the seroconversion study
      conducted after the outbreak, 89%, 100% and 50% of infants had detectable
      antibodies to types 1, 2, and 3, respectively, after four doses of OPV. Low
      responses to type 3 were also associated with the occurrence of sporadic cases of
      type 3 poliomyelitis in 1991, in spite of high rates of coverage with at least
      four doses of OPV (> 96%) throughout the country.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8282477
TI  - Q fever is absent from New Zealand.
AB  - To investigate the presence of Coxiella burnetii in sheep and cattle, the two
      major ruminant populations of New Zealand, its seroprevalence was determined in
      aborting cattle and sheepdogs. These groups of animals were chosen because of
      their accessibility and the fact that they would be good indicators for the
      presence of the organism. A total of 2181 bovine and 12,556 canine samples were
      all seronegative. On the basis of these results and previous reports it is argued
      that New Zealand is free of coxiellosis or Q fever.

PMID- 8282478
TI  - Methods for calculation of follow-up rate in a cohort study.

PMID- 8282479
TI  - T-cell receptor V beta 8 has no significant suppressive effect on collagen
      induced arthritis.
AB  - To elucidate the in-vivo role of T lymphocytes in collagen-induced arthritis
      (CIA), treatment with anti-CD4 or anti-T-cell receptor (TCR) V beta 8 monoclonal
      antibody (mAb) was performed in CIA mice. As the result of injection with each
      mAb, CD4-positive cells were incompletely deleted in the peripheral blood and
      lymph nodes, whereas TCR-V beta 8-positive cells were completely deleted. In the
      anti-CD4-mAb-treated mice, the development of arthritis was markedly suppressed
      in association with a lower antibody response to type II collagen. However, the
      treatment with anti-TCR-V beta 8 mAb did not alter either the arthritis symptoms
      or the antibody response. These results suggest that the development of arthritis
      is regulated by T cells, most probably CD4-positive cells, and not by TCR-V beta
      8-positive cells.

PMID- 8282480
TI  - Normalization of depressed natural killer activity after interferon-alpha therapy
      is associated with a low frequency of relapse in patients with chronic hepatitis
      C.
AB  - In the present study, we found that human recombinant interferon-alpha (rIFN
      alpha) given at a dose of 3 x 10(6) units thrice weekly for three months, and 1.5
      x 10(6) units thrice weekly for the next three months, was able to restore
      depressed natural-killer (NK) activity to normal values in 12 out of 21 chronic
      hepatitis C patients positive for anti-HCV antibodies. In all of these patients,
      NK normalization was still sustained after three months from suspension of
      therapy. Eighteen patients also showed a normalization of the alanine
      aminotransferase (ALT) level by the end of treatment (responder patients),
      independently of changes in NK activity. No significant improvement in either NK
      activity or aminotransferase levels was seen among 20 untreated patients. In 8
      responder patients (1 with normalized and 7 with low NK activity), ALT levels
      returned to pre-therapy values within three months after suspension of rIFN-alpha
      administration (relapse). We found that patients who normalized NK activity had a
      lower frequency of relapse as compared to patients with low NK activity by the
      end of treatment (p > 0.01). Immunofluorescence analysis of biopsy-derived liver
      tissue revealed that rIFN-alpha was able to induce strong MHC class I antigen
      expression on hepatocytes of treated patients, but this was not related to the
      clinical course.

PMID- 8282481
TI  - Reduction of postischaemic ventricular dysfunction and arrhythmias by trapping
      hydroxyl radicals with salicylic acid.
AB  - Recent studies have suggested the ability of salicylic acid (SA) to trap the
      hydroxyl radicals (.OH) generated in reperfused ischaemic myocardium. This study
      was designed to examine the effect of SA on reperfusion-induced arrhythmias and
      postischaemic ventricular dysfunction. Isolated rat hearts perfused by the
      Langendorff technique were preperfused with SA for 10 min. Hearts were then made
      ischaemic for 30 min, followed by 30 min of reperfusion. The left-ventricular
      contractile functions, including left-ventricular developed pressure (LVDP) and
      its first derivative (LV dp/dt), and creatine kinase (CK) release, were
      determined before and after ischaemia. Epicardial electrocardiograms (ECG) were
      also employed to analyse the incidence of ventricular tachycardia (VT) and
      ventricular fibrillation (VF). SA improved LVDP and LV dp/dt, and reduced CK
      release, as compared to the control group (p < 0.05). The incidence of VT and VF
      during reperfusion was also significantly reduced by SA (p < 0.05). Analysis of
      tissue thiobarbituric acid-reactive products indicates that SA decreased
      oxidative stress during reperfusion. In conclusion, these results suggest that SA
      reduces ventricular dysfunction and attenuates ventricular arrhythmias by
      trapping OH radicals upon reperfusion in isolated rat hearts.

PMID- 8282483
TI  - Human neonatal ovary: proposal of a three-dimensional model.
AB  - A model of human neonatal ovary is presented, derived from morphometric,
      evaluations carried out on left ovaries removed from five full-term neonates with
      a 46, XX karyotype, free from malformations of the genital apparatus. According
      to this model, the gonad can be represented by a triaxial ellipsoid with a
      central medullary core surrounded by a cortical stratum of constant thickness.
      The germinal population, consisting of follicles and primitive cortical tissue,
      occupies the cortex, intermingled with the interstitium or stroma. In the cortex
      it is then possible to describe an outer layer formed by primitive cortical
      tissue, and an inner portion occupied by follicles. The primary and secondary
      follicles fill the portion near the medulla and the primordial ones are contained
      in the middle and outer zones. Since the variability observed among ovaries is
      slight, we can propose a mean model of neonatal ovary in which the spatial
      relationships among the different components, the total number of follicles and
      their position in the cortex can be calculated.

PMID- 8282482
TI  - Role of M1 muscarinic receptor subtypes in mediating airway smooth muscle
      contraction.
AB  - Muscarinic receptor subtypes have been identified on airways of several mammalian
      species, including humans. They are distributed in the lung over submucosal
      glands, airway ganglia and over the nerves; M1-receptors are found in airway
      ganglia, M2-receptors (autoreceptors) are present in cholinergic postganglionic
      nerves at the prejunctional level, whereas the muscarinic receptor subtypes found
      in airway smooth muscle are of the M3-receptor subtype. We had previously
      reported the presence of M1-receptors on the smooth muscle of large and small
      airways of patients suffering from chronic bronchitis, but only is the peripheral
      airways of healthy subjects; one possible explanation of these results is that
      the bronchial epithelium may play a role in bronchial responsiveness to relaxant
      muscarinic antagonists. To clarify this hypothesis we have studied in vitro the
      responses to acetylcholine (ACh), and some muscarinic selective (pirenzepine, PZ;
      p-fluorohexahydrosiladyphenidol, pFHHSiD) and non-selective (atropine, ATR)
      antagonists, on human bronchial smooth muscle in the presence and in the absence
      of epithelium. The absence of epithelium did not modify the responsiveness to ACh
      to any great extent and did not change the responsiveness to relaxant
      antagonists. Our results show that the M1-receptors may play a role in mediating
      contraction of airway smooth muscle; research is in progress regarding their
      function in disease.

PMID- 8282484
TI  - [Conventional roentgen procedures in pneumology].

PMID- 8282485
TI  - [Ultrasound diagnosis in pneumology].

PMID- 8282486
TI  - [Nuclear medicine methods in pneumology].

PMID- 8282487
TI  - [The value of computerized tomography in pneumologic imaging diagnosis].

PMID- 8282488
TI  - [Value of magnetic resonance tomography in pneumology].

PMID- 8282489
TI  - [25-year-old patient with short stature and male habitus with absent testes].

PMID- 8282490
TI  - [25-year-old patient with febrile infection, thrombopenia and hemolysis].

PMID- 8282491
TI  - [Unfractionated standard heparin versus low molecular weight heparins].

PMID- 8282492
TI  - [What are the indications for interferon therapy with regard to the significance
      of serologic and histologic findings and laboratory data?].

PMID- 8282493
TI  - [What is the origin of nocturnal blood pressure drop in treatment with a long
      acting ACE inhibitor?].

PMID- 8282494
TI  - [The physician and accidents. Legal and medical problems].

PMID- 8282495
TI  - Effects of contrast agents on renal function.
AB  - RATIONALE AND OBJECTIVES: Contrast-induced changes produced in normal renal
      function are discussed, and possible mechanisms by which such changes may occur
      are described. Animal experiments are reviewed, with the dog model providing
      results most closely approximating observations in humans. METHODS: In the
      previous studies considered, standard clearance techniques were used to assess
      glomerulo-vascular changes, while urinary enzyme and protein excretions, along
      with changes in tubular reabsorption of electrolytes, were examined as indirect
      measures of contrast-induced tubular effects. The selection of papers for review
      was based primarily on studies conducted in large animals and humans. To be
      incorporated, traditional studies regarding accepted methods of analyzing renal
      function that did not involve extensive surgical preparation were reviewed.
      RESULTS: Renal vascular effects of contrast media induce a biphasic change in
      renal blood flow--a brief increase followed by a more prolonged decline--the
      magnitude of which varies by dose and route of administration. Tubular effects
      include increased excretion of cytosolic enzymes plus changes in tubular
      reabsorption of sodium, potassium, and chloride. A transient osmotic diuresis
      also occurs. CONCLUSIONS: Changes in renal blood flow, glomerular filtration
      rate, urinary electrolyte and solute excretion, and modification of the urinary
      concentrating-diluting mechanisms have yielded insights into the tubulo
      glomerular actions of contrast media. The link between acute renal effects and
      subsequent contrast-associated nephropathy, while not absolutely defined, is
      becoming better understood as new information is gained using experimental models
      that more closely approximate high-risk states, including states of volume
      depletion, circulatory insufficiency, and pre-existing renal damage. Current
      attention is focused on the tubulo-glomerular feedback mechanism as accounting
      for the renal effects of contrast media.

PMID- 8282496
TI  - Update on safety. International assembly on the clinical safety of 10 years of
      use of nonionic contrast media. St. Thomas, United States Virgin Islands, May 5
      7, 1993. Proceedings.

PMID- 8282497
TI  - Low-osmolar contrast media in the 1990s. Guidelines for urography in a cost
      sensitive environment.
AB  - OBJECTIVES: The author reviews the clinical, ethical, medicolegal, and economic
      consequences of the routine versus limited use of low-osmolar contrast media for
      patients undergoing urographic and other radiologic studies. METHODS: A
      comprehensive review of the literature since the introduction of low-osmolar
      contrast media was conducted, focussing on medical decision making and the
      economic impact of those decisions on radiologic studies requiring the
      administration of water-soluble contrast agents. RESULTS: Compared with high
      osmolar ionic contrast media, routine use of low-osmolar agents for intravascular
      injection during diagnostic imaging results in fewer idiosyncratic reactions in
      patients and potentially less renal injury in a subgroup of critically ill
      patients. The high cost of low-osmolar agents relative to the overall cost of the
      examination has prevented the universal adoption of this class of agents in the
      United States. CONCLUSIONS: Economic pressures on private and government-based
      insurance plans, as well as on managed-care systems responsible for a variety of
      patient populations, continue to limit the availability of low-osmolar agents to
      the individual patient.

PMID- 8282498
TI  - Nonionic contrast media. Procoagulants or clotting innocents?
AB  - OBJECTIVES: Compared with ionic contrast media, nonionic contrast media cause
      fewer adverse reactions, including hemodynamic and electrophysiologic
      complications, and are better tolerated by patients. However, concern as to
      whether nonionic agents are associated with more thromboembolic complications has
      been raised in recent years. This article reviews in-vitro and in-vivo
      coagulation studies with nonionic contrast media, including the authors' current
      study using blood samples from percutaneous transluminal coronary angioplasty
      (PTCA) patients. METHODS: Articles for this review were selected on the basis of
      providing viewpoints representative of both sides of the clotting controversy
      involving nonionic contrast media. In addition, articles were selected that, in
      toto, include the several relevant aspects of thrombosis during PTCA: whole blood
      clotting, angiography catheters, angiography syringes, rheology, and vascular
      endothelium. The preliminary work described used platelet adhesion/aggregation to
      a collagen-coated surface under controlled conditions of heparinized, whole blood
      flow. Adhesion/aggregation was quantified by digital analysis of real-time images
      obtained by epifluorescence videomicroscopy. In parallel studies, changes in
      markers (membrane glycoproteins) of platelet activation were measured using whole
      blood flow cytometry. RESULTS: Although nonionic contrast media are weaker
      anticoagulants than ionic contrast media, no convincing evidence demonstrates
      that they are procoagulant. On the contrary, in-vitro studies suggest that ionic
      media may weaken the antithrombotic properties of vascular endothelium by direct
      endothelial injury. Certain clinical trials of PTCA patients substantially
      challenge the use of nonionics. Yet, Grabowski et al found no evidence of
      platelet activation by ioxaglate or iohexol in preliminary work. This result was
      obtained with two of the most sensitive platelet assays available: flowing whole
      blood aggregometry and whole blood flow cytometry. Attention should be given to
      the adequacy of heparinization in future clinical studies. CONCLUSIONS: Nonionic
      contrast media are not procoagulant in vitro in the hands of most research
      groups. The focus of current controversy, therefore, is whether there is a
      clinical and in-vivo difference in thrombotic events seen with nonionic versus
      ionic media during PTCA. Elements in this controversy include platelet
      activation, blood-foreign surface (catheter and syringe) interaction, rheology,
      vascular endothelium, and adequacy of heparinization.

PMID- 8282499
TI  - The clotting issue: etiologic factors in thromboembolism. I. Chemistry,
      pharmacology, and toxicity of angiographic contrast agents.
AB  - RATIONALE AND OBJECTIVES: In a decade of clinical use of nonionic contrast
      agents, only one scientific criticism of any significance has been leveled at
      them. That is, they may increase the risk of thromboembolism in diagnostic and
      interventional clinical angiography. The author examines the hypothesis that
      contrast molecules exert their intrinsic toxicity through hydrophobic and Coulomb
      interactions with biological molecules. Because nonionic molecules are
      hydrophilic and have no charge and therefore no Coulomb component, they should be
      less toxic. METHODS: The basic chemical and pharmacologic properties of iodinated
      contrast agents are outlined and their effects on hematology are discussed. The
      author also reviews studies on the development of ionic and nonionic agent
      formulations and the evolution of theories on their toxicity. The relative
      toxicity of ionic versus nonionic agents also is considered. RESULTS: Three
      factors are found to correlate well with contrast toxicity: partition
      coefficient, protein-binding capacity, and pi-electron density in the benzene
      ring system. Any increase in pi-electron density increases hydrophobicity, while
      any reduction in pi-electron density decreases hydrophobicity. The more
      hydrophobic molecules have a lower osmolality. Nonionic agents are observed to
      exhibit lower toxicity than low-osmolality ionic agents. Because of their greater
      hydrophilicity, based on better masking of the hydrophobic core by hydrophilic
      side chains, and their lack of charge, nonionic contrast agents have a reduced
      potential for interactions, rendering them more inert and less toxic. The
      uniformity of results in the different systems previously studied and the
      constant hierarchy of relative effects are striking. CONCLUSIONS: Fundamental
      understanding of the molecular basis of contrast toxicity indicates that it is
      not possible to synthesize a contrast molecule that will have strong
      anticoagulant effects and yet retain a low toxicity. Having marked anticoagulant
      effects is an indicator of toxicity: a more anticoagulant agent is more toxic. It
      is similarly not possible to manipulate incipients in the formulations to achieve
      strong anticoagulant properties without also modifying toxicity. There also is a
      trade-off between reducing chemotoxicity and reducing osmolality, since, if we
      successfully shield the hydrophobic core of the molecule, we limit the degree to
      which the osmolality of the solution will be reduced below that predicted on
      simple chemical considerations. These then are the essential points to bear in
      mind in any discussion of the clotting issue. For reasons of their structure and
      the nature of additives in their formulations, second-generation nonionic agents
      have little effect on biological systems. Therefore, they have only a limited
      impact on the coagulation cascade exactly in line with their low toxicity.
      Consequently, nonionic contrast agents have established themselves, with both
      radiologists and patients, as the agents of choice and are now accepted as better
      tolerated and safer than ionics--in terms of both a reduced incidence of
      idiosyncratic/anaphylactoid reactions and high-dose tolerance--in interventional
      radiology and pediatrics.

PMID- 8282500
TI  - The clotting issue: etiologic factors in thromboembolism. II. Clinical
      considerations.
AB  - RATIONALE AND OBJECTIVES: The authors analyze the origins of the "clotting
      issue," the controversy that began in the 1980s when contrast media, once
      perceived as good flushing agents for catheters because of their assumed
      anticoagulant properties, came under attack for allegedly causing
      thromboembolism. Laboratory studies as well as a number of clinical reports
      seemed to substantiate this charge. Nonionic agents in particular were accused by
      some clinicians of being more likely to cause clots to form in syringes
      contaminated with blood than were ionic agents. The authors wanted to determine
      whether some lapse in operator technique rather than a fault in the contrast
      agent might be to blame. The theory that the syringe and catheter materials, and
      not the contrast agent itself, could be the source of thromboembolic problems in
      angiography also is examined. METHODS: The authors reviewed studies and reports
      on both sides of the issue and conducted laboratory and clinical studies of their
      own. For the syringe materials analysis, they used a fibrinopeptide A (FpA)
      enzyme-linked immunosorbent assay (ELISA) test to monitor levels as a marker of
      activation of coagulation. They tested catheter materials using the same
      technique. RESULTS: Clots were found only in nonionic agents, but under
      nonclinically relevant circumstances. If the anticoagulant effect of the nonionic
      contrast agent was maximized by mixing rather than layering blood and agent,
      clots did not form. In their materials analysis, the authors demonstrated that
      glass syringes are thrombogenic, causing vigorous contact activation, and that
      plastic is less so. Polyurethane catheters are more thrombogenic, polyethylene
      less so. One survey conducted in the 1970s on the clinical incidence of
      thromboembolism in coronary angiography suggested that the single most important
      factor in the etiology is poor angiographic technique. The authors' studies
      supported their thesis. CONCLUSIONS: In terms of the findings from laboratory
      studies, misinterpretation of data by nonclinicians is one problem. No evidence
      suggests that nonionic contrast agents are in any way prothrombotic or
      thrombogenic. On the contrary, in line with their greater inertness, nonionic
      agents have weaker effects. Ionic contrast media may cause more endothelial
      injury and associated localized platelet deposition than nonionic contrast media,
      and more anticoagulant contrast agents are more toxic. If anticoagulation is
      required, therefore, it should be achieved by such procedures as carefully
      controlled systemic heparinization rather than by resorting to more toxic
      materials. The activation of coagulation is caused by endothelial injury and by
      prolonged contact between blood and foreign surfaces such as syringes or
      catheters, but is inhibited by the contrast agent. Because a thrombus may form
      inside the catheter, whatever contrast agent is used, flushing is important. The
      authors agree with the findings of one study that the incidence of
      thromboembolism in coronary angiography, and probably in other catheter
      procedures, is markedly operator dependent. The materials of the syringes and
      catheters used, as well as the state of the patient's intrinsic clotting, are
      more important factors than the contrast agent. The authors conclude that
      materials other than the contrast agents are the cause of thromboembolic
      problems; and that, being anticoagulant, contrast agents are entirely helpful, if
      variably so, in angiographic procedures.

PMID- 8282501
TI  - Safety of nonionic agents in visceral angiography.
AB  - RATIONALE AND OBJECTIVES: To compare the safety of ionic and nonionic contrast
      agents in visceral angiography. METHODS: Beginning in 1989, a prospective, open
      trial was begun, and 1,890 patients who have undergone contrast injection were
      enrolled. Patients considered to be high risk were graded according to Palmer and
      received nonionic contrast media, while all other patients received ionic
      contrast media. RESULTS: Because of the small number of visceral angiography
      procedures performed (38), no definitive conclusions could be drawn as to the
      differences between ionic and nonionic agents regarding grade-2 and grade-3
      adverse events. However, a difference in grade-1 events was apparent in favor of
      nonionic agents. CONCLUSIONS: More than 10 years ago, the Department of Radiology
      staff at Aker Hospital began using iohexol, first in infants, then in children,
      pregnant women, patients undergoing leg phlebography, and patients with serious,
      previously documented reactions from contrast media. Currently, the department
      staff administers nonionic agents exclusively for coronary angiography and other
      cardiac procedures in approximately 300 patients per year. Today, use of nonionic
      contrast media is the standard for almost all procedures requiring intra-arterial
      or intravenous application.

PMID- 8282502
TI  - The physiologic effects of nonionic contrast media on the heart.
AB  - OBJECTIVES: This article briefly reviews the potential physiologic effects of
      ionic versus nonionic contrast media on the myocardium. METHODS: Selection
      criteria for articles included the use of quantitative measurement techniques,
      controlled contrast-media doses, and a focus on cardiac mechanical or electrical
      function. Two important reviews also were used. Most of the data considered
      represent the results of animal experiments. RESULTS/CONCLUSIONS: Nonionic
      monomer contrast media are associated with markedly less physiologic effect on
      the heart, compared with ionic agents. For instance, cardiac depression is
      minimal, and the incidence of arrhythmia and fibrillation is reduced with
      nonionic agents during coronary arteriography. Nonionic dimer agents with
      electrolyte supplementation produce even less mechanical and electrical
      disturbances.

PMID- 8282503
TI  - Nonionic contrast use in cardiac angiography.
AB  - OBJECTIVES: This article reviews the safety profile of nonionic versus ionic
      contrast media, focussing on those aspects specific to the cardiac
      catheterization laboratory. DATA ANALYZED: Comparative electrophysiologic and
      hemodynamic effects, nephrotoxicity, thrombosis-related complications, and other
      possible adverse effects are discussed. Volume limitations and approaches to
      efficient use of nonionic agents also are considered. RESULTS: Previous
      investigations indicate that cardiac electrophysiologic and hemodynamic effects
      are less with nonionic contrast media than with conventional high-osmolar ionic
      agents. Studies assessing potential adverse reactions suggest an advantage with
      nonionics, compared with high-osmolar ionic agents, mostly regarding reduction in
      mild-to-moderate adverse events. In general, studies on the risk of
      nephrotoxicity among cardiac angiography patients demonstrate no difference
      between nonionic and ionic contrast or a slight beneficial effect with nonionics
      among those with pre-existing renal dysfunction. There is no convincing evidence
      for an increased incidence of thrombosis-related events with nonionic agents
      during coronary angiography and data regarding nonionic contrast-related
      thrombosis in patients undergoing coronary angioplasty are conflicting.
      CONCLUSIONS: At the present time, there is no justification for avoiding nonionic
      contrast agents based on the risk of thrombosis. Research findings on the effect
      of contrast volume are also inconclusive.

PMID- 8282504
TI  - The use of nonionic contrast agents in neuroangiography. A review of the
      literature and recommendations for clinical use.
AB  - RATIONALE AND OBJECTIVES: Several large studies have demonstrated the improved
      safety record of nonionic versus ionic contrast agents for intravenous
      administration. However, nonionic agents are much more expensive than ionic
      agents. The author addresses whether, given this large cost differential,
      nonionic contrast agents should always be used in neuroangiography (cerebral and
      spinal cord angiography and intravascular neurointerventional procedures). The
      answer could come from a closer examination of the effects of contrast agents on
      the brain. METHODS: There have been a number of animal experiments and clinical
      trials performed using a variety of available intravascular contrast agents. In
      an attempt to arrive at some reasonable conclusions regarding the use of contrast
      agents today, the author reviews several of these studies. In the human studies,
      three areas were analyzed: 1) cerebral angiography, 2) spinal cord angiography,
      and 3) intravascular neurointervention. The author explains why demonstrating the
      effect of a contrast agent on the brain or spinal cord in the clinical setting is
      more difficult than studying the effect of this agent on the liver, heart, or
      kidney. For example, obtaining objective measurements of altered cerebral
      physiology following intravascular injection of a contrast agent may itself alter
      the physiology. In lieu of objective measurements, investigators must rely on
      apparent changes in behavior, mentation, or the production of a focal neurologic
      deficit. However, it is extremely difficult, if not impossible, to separate the
      effect of the contrast agent from the effects of the arteriographic procedure, or
      from the disease process being evaluated. RESULTS: The neuronal environment is
      protected by the blood-brain barrier. A number of animal experiments have
      demonstrated that nonionic agents produce breakage of the blood-brain barrier
      less frequently than do ionic agents. In these studies, nonionic agents also
      produced fewer neurologic effects than did ionic agents. The human studies showed
      no statistically significant differences in neurologic effects when ionic and
      nonionic agents were compared. Cerebral: minor changes in heart rate were more
      common with ionic than with nonionic agents; there were no significant
      electroencephalogram changes in any of the patients studied. Spinal cord: the
      effects of intravascular injections of contrast material into the spinal cord of
      experimental animals have been rarely evaluated; direct comparisons of contrast
      agents in human spinal cord angiography have not been performed.
      Neurointervention: there have been no comparative studies of different contrast
      agents used during intravascular neurointerventional procedures in humans.
      CONCLUSIONS: Extensive animal data demonstrate that nonionic contrast agents are
      safer than ionic for cerebral angiography. Animals in the cited studies show less
      blood-brain barrier disruption, fewer direct neuronal effects, and fewer
      neurobehavioral deficits. However, the overwhelming conclusion from the human
      studies is that, while there is evidence in the experimental animal that nonionic
      agents produce fewer neurologic effects than do ionic agents, no study to date
      has been able to translate these findings into an apparent clinical difference in
      humans, mainly because it's so difficult to detect and measure neurologic changes
      in human trials. In addition, differences in neurologic effects between contrast
      agents used in human studies may be relatively small. Thus, one must make an
      educated guess as to the appropriate use of contrast agents in the context of
      their apparent clinical safety and cost-benefit ratio.

PMID- 8282505
TI  - The role of nonionic myelography in the diagnosis of lumbar disc herniation.
AB  - RATIONALE AND OBJECTIVES: The accuracy and safety of nonionic myelography,
      unenhanced computed tomography (CT), and magnetic resonance (MR) in the diagnosis
      of lumbar disc herniation are reviewed. The comparative costs of these tests are
      also considered. METHODS: The accuracy of imaging tests that diagnose disc
      herniations was established by conducting a Medline search between 1985 and 1992.
      The morbidity associated with these tests are less formally established from
      selected articles. Finally, the mediocre reimbursement rates of these tests are
      reviewed. RESULTS AND CONCLUSIONS: The evolution of nonionic contrast media from
      the first to the second generation has been accompanied by a notable decrease in
      adverse reactions. Although nonionic myelograms are now better tolerated by
      patients, noninvasive imaging with CT and MR imaging has become as accurate as or
      more accurate than lumbar myelography, and should replace it as a screening test.
      Computed tomography may have advantages over MR imaging when issues of
      availability and cost are considered. In contrast to lumbar myelography, CT
      myelography may continue to be a useful method for clarifying ambiguous results
      of noninvasive tests. The morbidity associated with CT myelography can be
      minimized by using low doses of a nonionic agent, keeping the patient well
      hydrated, and using a small lumbar puncture needle. The incidence of adverse
      reactions can be expected to decrease further as new nonionic dimers become
      clinically available.

PMID- 8282506
TI  - Is the safety of contrast agents an issue in body computed tomography?
AB  - RATIONALE AND OBJECTIVES: To investigate the comparative safety profiles of
      nonionic and ionic contrast agents in body computed tomography (CT) studies.
      METHODS: A literature search was conducted to examine the following variables:
      image quality, repeat or aborted studies, and the cost of nonionic agents versus
      benefits. Data are presented that address the following questions: Does
      administering nonionic agents save time? Are nonionic agents more likely to
      provide an adequate study? Does an adequate study necessarily ensure an improved
      detection rate? RESULTS: The administration of nonionic contrast does not save
      time during the body CT studies. There is little significant difference between
      the sensitivity for making a diagnosis when using an ionic or nonionic agent.
      CONCLUSION: The lack of difference in diagnostic sensitivity or time to perform a
      study between ionic and nonionic agents does not warrant the conversion to
      nonionic agents in body CT.

PMID- 8282507
TI  - Low-osmolality contrast media and the risk of contrast-associated nephrotoxicity.
AB  - OBJECTIVES: The authors review clinical data, including those from the recent
      Iohexol Cooperative Group trial, regarding the nephrotoxic potential of low
      osmolar versus high-osmolar contrast media. The clinical characteristics and
      postulated mechanisms of contrast-associated nephrotoxicity are also considered.
      METHODS: The principal strategy for identifying relevant articles was to search
      the MEDLINE database using the MeSH heading "contrast media nephrotoxicity."
      Articles from 1966 through 1992 that were considered included original research
      papers as well as reviews. Those articles selected for detailed review documented
      original research pertaining to use of low-osmolar or high-osmolar agents.
      Selected abstracts for pertinent society meetings were also used. No attempt was
      made to be complete in describing the field. Rather, specific articles that
      selectively address the question of nephrotoxicity related to the osmolar content
      of contrast media were used for discussion. RESULTS AND CONCLUSIONS: In-vitro and
      animal studies indicate that renal changes possibly involved in the pathogenesis
      of contrast-associated nephrotoxicity seem to be ameliorated with low-osmolar
      contrast media, compared with high-osmolar agents. Several recent clinical
      trials, as well as a meta-analysis combining 24 randomized studies, suggest that
      the risk of contrast-associated nephrotoxicity is similarly low with high-osmolar
      and low-osmolar agents among otherwise stable patients with normal renal
      function, but that low-osmolar contrast is less nephrotoxic than media with high
      osmolality in patients with pre-existing renal insufficiency.

PMID- 8282508
TI  - Contrast bolus dynamic computed tomography for the measurement of solid organ
      perfusion.
AB  - RATIONALE AND OBJECTIVES: The authors have investigated the aortic responses to
      various intravenous bolus injections of nonionic and ionic contrast media and
      have presented data illustrating the potential of ultrafast computed tomography
      (CT) to quantify perfusion in the kidney, liver, and spleen. METHODS: Bolus
      Dynamics Study: Performed in 3 healthy dogs (weight: 35 kg to 36 kg). In 2 dogs,
      15 mL of the nonionic agent iohexol and the ionic agent sodium-meglumine
      diatrizoate were injected at 5, 10 and 20 mL/sec via a venous catheter placed in
      the superior vena cava; the order of injection was alternated between the 2 dogs.
      In the third dog, 25 mL of iohexol 300 mg I/mL was compared with diatrizoate 370
      mg I/mL with injection rates of 10 and 20 mL/sec. Computed tomography scanning at
      the level of the midabdominal aorta was performed using an ultrafast CT scanner.
      Time-density curves were drawn for regions of interest over the aorta, and gamma
      variate fits performed. Perfusion Studies: Dynamic perfusion scans of the upper
      abdomen were performed in more than 50 patients. A dose of 25 mL of iohexol 300
      mg I/mL was injected at 10 mL/sec via an intravenous cannula in the antecubital
      fossa, followed immediately by 25 mL of saline, at the same rate. Scanning was
      performed at a single level using an ultrafast CT scanner. Regions of interest
      were drawn and gamma-variate fits were applied to the vascular time-density
      curves. RESULTS: Bolus Dynamics: Excellent curve fits for aortic time-density
      curves were obtained. A 10-mL/sec versus a 5-mL/sec bolus produced an 8% higher
      peak density. Nonionic contrast increased the peak density by a mean of 6%,
      increased the area under the corrected time-density curve by a mean of 22%, and
      lengthened the increase time by a mean of 21%. Perfusion Studies: Values obtained
      were reproducible and correlated well with values predicted from inert gas
      washout techniques. CONCLUSIONS: Changes in the CT number in a region after an
      intravenous injection of contrast medium may be used to calculate blood flow per
      unit volume of tissue. Ultrafast CT offers sufficient data points for accurate
      calculation. The quality of the aortic bolus is of great importance. Nonionic
      media offer several important advantages: hemodynamic perturbation is minimized,
      and they are better tolerated at the high injection rates needed. Low-osmolality
      nonionic agents produce "better" curves than conventional high-osmolality ionic
      agents, all other factors being equal. The resulting data are relevant to
      intravenous digital subtraction angiography and indirect portography as well as
      to perfusion measurement. The technique of quantitative dynamic CT is
      theoretically applicable to any cross-sectional modality, notably magnetic
      resonance.

PMID- 8282509
TI  - Functional imaging in computed tomography. The use of contrast-enhanced computed
      tomography for the study of renal function and physiology.
AB  - RATIONALE AND OBJECTIVES: Computed tomography (CT) numbers may provide the raw
      material for calculations of important physiologic parameters, such as organ
      regional perfusion and glomerular filtration rate. Because, except in cases of
      severe renal dysfunction, iodinated intravascular contrast agents are excreted
      primarily by passive glomerular filtration, the decline in their concentration in
      blood or tissues will reflect renal function. The time evolution of contrast
      agent distribution within the kidney, from blood to tubules, can also be seen as
      a measure of renal function. The authors illustrate how CT numbers may be
      employed to obtain useful data regarding renal function. METHODS: Two CT methods
      were used to yield information on renal function. Delayed CT: 2 hours after
      administration of 200 mL of a contrast agent (iohexol) for a routine CT, a
      patient with normal renal function was brought back to the scanner, and a single
      fixed section through the abdomen, including the psoas muscles, was imaged; the
      scan was repeated at 2, 3, and 4 hours. Large regions of interest were selected
      in soft tissue, and six measurements of CT numbers were taken and averaged for
      each time; after taking logs, these were plotted against time. Dynamic CT: A
      rapid bolus of 40 mL nonionic contrast agent was injected into an antecubital
      vein at 5 mL/sec. At a fixed level, images were taken through the center of the
      kidneys at 5-second intervals for 2 minutes after injection. The patient was
      allowed to breathe gently throughout the examination. Regions of interest were
      selected over the kidney and the aorta, and curves of CT numbers against time
      were generated; a Patlak plot was performed using the parameters measured. Using
      the renal CT numbers collected during the first 2 minutes after injection, it was
      possible to analyze the handling of the contrast agent and to obtain a measure of
      the glomerular filtration rate. RESULTS: Delayed CT: Data yielded good values for
      glomerular filtration rate; the typical patient illustrated had a glomerular
      filtration rate per unit extracellular fluid volume of 0.005 min-1. Dynamic CT:
      The correlation coefficient for the line fit was 0.97, a value typically found in
      these studies, indicating the efficacy and ruggedness of this method in spite of
      the patient's shallow breathing throughout the examination. CONCLUSIONS: Computed
      tomography offers the potential for quantitative and physiologic measurement that
      has not been widely explored. The problem with the delayed CT technique is that
      since measurements are made at 2 hours and onward, it is applicable only to
      patients who have received larger doses of contrast. Otherwise, the CT numbers
      are low and the measurement error, large. Also, bringing the patient back to the
      scanner 2 hours later may be inconvenient to both patient and radiologist, and
      may disrupt case scheduling. This method is, however, less inconvenient than the
      established blood-level measurement. The dynamic CT method yields a new measure
      of renal clearance, namely, clearance per unit volume of kidney. The
      disadvantages of this method are the radiation burden involved in repeated rapid
      CT scans and the fact that, if renal disease is uneven, a nonrepresentative slice
      could be chosen. Its advantages are its simplicity and that it can be completed
      within the first 2 minutes of a CT examination. It may be expected to have an
      interesting application to situations in which there is known renal disease.
      Although difficulties are associated with both of these techniques that could
      prevent their general adoption as clinical routines, they nevertheless should
      find application in selected patients and should prove useful research tools in
      the study of renal disease.

PMID- 8282510
TI  - A review of the toxicity of nonionic contrast agents in children.
AB  - OBJECTIVES: The safety of nonionic contrast agents with that of ionic iodinated
      contrast agents in children is compared. METHODS: A comprehensive literature
      search was conducted to identify all publications on the safety profile of
      nonionic contrast agents administered intravenously to children. This information
      was compared to published data on the safety of nonionic media in adults and on
      the safety of ionic agents in children. RESULTS: There appears to be strong
      evidence for increased safety of nonionic agents in children compared with ionic
      agents, although the published data reviewed are subject to methodological
      criticism. Moderately severe and minor reactions occur less frequently with
      nonionic agents. Deaths occur too infrequently to permit a valid evaluation.
      Contrary to previous beliefs, the incidence of adverse reactions in children
      appears to be similar to the incidence in adults. CONCLUSIONS: Although nonionic
      agents offer improved safety, it is still not clear whether this benefit
      justifies the associated costs, because conventional ionic agents are already
      extremely safe. However, it may be possible to justify the increased cost of
      nonionic agents in children based solely on the reduction of minor reactions.
      Data regarding the safety of nonionic agents in children are limited, and large,
      prospective studies are warranted.

PMID- 8282511
TI  - Rates of idiosyncratic reactions. Ionic versus nonionic contrast media.
AB  - RATIONALE AND OBJECTIVES: Nearly 40 years ago, investigators began collecting
      data regarding idiosyncratic reactions to iodinated contrast agents. The rates of
      idiosyncratic reactions in patients receiving ionic contrast agents are compared
      with those found in patients receiving nonionic agents. METHODS: A comprehensive
      literature review was conducted. Retrospective and prospective studies were
      included, as well as recent analytical multistudy reviews. RESULTS: For
      conventional hypermolar agents, rates are estimated to be 5% and the rate of
      repeat reactions, greater than 20%. Large comparative studies conducted in the
      late 1980s found significantly lower rates of idiosyncratic reactions with the
      newer, nonionic agents than with conventional agents. The results of studies
      evaluating the use of routine administration of steroids before the use of ionic
      agents have been contradictory. Two analytical reviews of earlier research find
      fault with the methodology of most studies, but the reviewers supported the
      increased safety of nonionic agents. CONCLUSIONS: All iodinated contrast media
      have excellent safety records. Most evidence, however, demonstrates that nonionic
      agents are safer than ionic agents.

PMID- 8282512
TI  - Coping with violence.

PMID- 8282513
TI  - Andy and David ... a personal look at two special needs' children. David.

PMID- 8282514
TI  - Andy and David ... a personal look at two special needs' children. Andy.

PMID- 8282516
TI  - First freestanding hospice inpatient unit established in Iowa.

PMID- 8282515
TI  - Board goal is to pursue highest standards for physicians.

PMID- 8282517
TI  - Iowans with intestinal bypass--a status report.

PMID- 8282518
TI  - On the "disappearance" of hysteria. A study in the clinical deconstruction of a
      diagnosis.

PMID- 8282519
TI  - Evoked potentials in hereditary spastic paraplegia.
AB  - Pattern reversal visual evoked response (VER) and monaural stimulation of
      brainstem auditory evoked responses (BAER) were recorded from both sides in 25
      patients (males 19; females 6) with hereditary spastic paraplegia (HSP). Their
      age ranged from 15-52 (mean +/- SD; 25.2 +/- 22.5) years and duration of symptoms
      6 months-9 (mean +/- SD; 4.2 +/- 3.6) years. A prolonged P100 latency was seen in
      6 patients and BAER abnormality in 13. None of the patients had clinical evidence
      of brainstem involvement. It is suggested that VER and BAER abnormalities are due
      to segmental demyelination and fiber loss in central conduction pathways and
      could serve as an important tool for the diagnosis of this disorder.

PMID- 8282520
TI  - Cardiovascular reflexes in Parkinson disease.
AB  - We have investigated the autonomic function of 95 patients with Parkinson disease
      (PD) by testing their cardiovascular reflexes and compared the results with those
      of 53 healthy volunteers. 51.1% of the patients were on antiparkinsonian therapy.
      The patients showed a smaller heart rate response to deep breathing with a mean
      exhalation-inspiration difference of 87.73 +/- 7 (p: 0.0005), a smaller heart
      rate response to standing with a mean 30: 15 index of 1.18 +/- 0.25 (p: 0.01),
      and a smaller blood pressure rise to handgrip with a mean rise of 9.53 +/- 8.76
      mmHg (p: 0.005). We found a higher percentage of patients with established
      sympathetic lesion (41% vs 34%) or atypical patterns of global autonomic function
      involvement (33% vs 26%), but the percentage of subjects with parasympathetic
      lesion was similar in both, patients and controls (16% vs 15%). We found no
      significant difference on cardiovascular performance between treated and
      untreated patients. The patients with autonomic impairment were older than the
      patients with normal autonomic function. Our findings suggest that patients with
      PD have a true autonomic dysfunction.

PMID- 8282521
TI  - Pharmacokinetic and pharmacodynamic characteristics of a controlled-release
      formulation of trazodone versus the conventional formulation in healthy
      volunteers.
AB  - The pharmacokinetic and pharmacodynamic characteristics of a controlled-release
      (CR) formulation of trazodone were evaluated in healthy subjects who received
      acutely 150 mg and 75 mg of the CR trazodone and equal amounts of the
      conventional formulation on separate occasions. Plasma trazodone concentrations
      were measured by HPLC. The pharmacokinetic profile of CR trazodone was
      characterized by a slower increase in drug plasma levels and a lower and retarded
      peak plasma concentration without any modification in the total amount of
      trazodone absorbed over 24 hrs. The side effects were less severe and less
      frequent than with the conventional formulation.

PMID- 8282522
TI  - Symptomatic spinal arachnoid cyst in an elderly subject.
AB  - We report an unusual case of idiopathic thoracic intradural arachnoid cyst
      causing a chronic progressive spastic paraparesis in a 72 year old man. Symptoms
      completely resolved after surgical excision of the cyst.

PMID- 8282523
TI  - Hyperammoniemic coma in an adolescent girl: an unusual case of ornithine
      transcarbamylase deficiency.
AB  - Ornithine transcarbamylase deficiency (OTCD) is caused by an alteration of urea
      synthesis, linked with partial modification of the X-chromosome, whose clinical
      manifestations are: lethargy, nausea, vomiting and cerebral edema. While in
      newborn males OTCD presents with hyperammoniemia leading to cerebral palsy with
      profound neurological impairment and eventually death, in women who are healthy
      carriers, it is possible to detect the disorder only through specific tests,
      since heterozygote women are rarely symptomatic. We describe the case of a young
      woman admitted to the hospital after an episode of mental confusion with vomiting
      and psychomotor restlessness, which had previously occurred several times during
      the premenstruum and lasted a few hours. A 2 day history of stupor made admission
      mandatory. Tests carried out during the hospital stay showed marked
      hyperammoniemia and unconjugated hyperbilirubinemia, marked cerebral edema
      documented by a CT scan. Liver biopsy and CSF test were normal. Screening of
      plasma and urinary aminoacids, level of orotic acid in the urine and OTC activity
      in the liver, confirmed the diagnosis of OTCD. The possibility of early diagnosis
      and therapy of a disease which otherwise leads to death, emphasizes the
      importance of precise evaluation of a possible organic cause of anorexia and
      behaviour disorders in young women.

PMID- 8282524
TI  - A case of syncope on olfactory stimulation.

PMID- 8282525
TI  - Hachinski's ischemic score and the diagnosis of vascular dementia: a review.
AB  - The Hachinski ischemic score (HIS) scale is a simple clinical tool proposed and
      currently used for differentiating types of dementia (primary degenerative,
      vascular or multi-infarct, mixed type). Criteria for rating the items of the HIS
      were never given, or inter-observer reliability in applying it has never been
      tested. However, the studies which estimated the validity of this scale in
      predicting the true diagnosis (clinical/CT or neuropathological definition)
      demonstrated acceptable sensitivity and specificity in defining degenerative or
      vascular dementia. This scale seems unable to define mixed type dementia or
      subtypes of vascular dementia. Our review supports the use of the HIS in
      epidemiological studies on dementia.

PMID- 8282526
TI  - Typical trigeminal neuralgia associated with posterior cranial fossa tumors.
AB  - A clinical diagnosis of typical trigeminal neuralgia does not rule out the
      possibility of a space-occupying lesion compressing the nerve along its course
      from the brainstem to Meckel's cave. 4 cases of typical trigeminal neuralgia,
      treated medically for several years and seen here recently before a space
      occupying lesion was found in the posterior cranial fossa, point up the need for
      thorough neurological and neuroradiological examination of all patients with the
      typical symptoms. Lesion removal resulted in total relief from pain in 3
      patients. In the fourth patient the pain was controlled by percutaneous surgery
      with thermocoagulation of the gasserian ganglion.

PMID- 8282527
TI  - Clinical features and MR imaging in children with repaired myelomeningocele.
AB  - The aim of the study is to define the role of associated malformations in the
      clinical evolution of children affected by myelomeningocele. MRI investigation of
      the spinal cord was carried out on 25 patients between the age of 7.3 and 18.10
      with MMC repaired and followed up for at least 7 years. The relation between
      associated malformations demonstrated by MRI and clinical trend was analysed. The
      results are the following: 1) presence of asymptomatic tethered cord in all
      cases; 2) high frequency (92%) of Chiari malformation; 3) presence of
      syringomyelia in 20% of patients, symptomatic in 1; 4) presence of ventricular
      enlargement in 72% of cases without increased intracranial pressure syndrome. For
      a better therapeutic approach prospective MRI studies are needed in order to
      follow up associated malformations.

PMID- 8282528
TI  - IgG2 deficiency in children with febrile convulsions: a familial study.
AB  - The IgG subclasses were investigated in children with febrile convulsions (FC)
      and in their first degree relatives in the search for a selective immunological
      deficiency associated with FC and its occurrence in the relatives of affected
      subjects. The results of the study show lower IgG2 concentrations in FC patients
      than in controls. But it was not possible to demonstrate familial transmission of
      the IgG2 subclass deficiency, since it was present only in children with FC and
      tended to normalize in adulthood. The immunoglobulin subclass deficiency might be
      responsible for the recurrent infections connected with FC.

PMID- 8282529
TI  - Sleep related breathing patterns in patients with spinal muscular atrophy.
AB  - A clinical and polygraphic study of nocturnal sleep was performed in 8 (4 males,
      4 females; age range 10-37 years) patients with spinal muscular atrophy, whose
      baseline respiratory function assessment during wakefulness showed restrictive
      ventilatory syndrome but blood-gas tension within normal limits. No patient
      reported any significant sleep complaint suggestive of sleep-disordered
      breathing. However, in 4 patients HbSaO2 desaturations below 90% (HbSaO2 nadir
      68%) were detected during nocturnal polysomnography. The HbSaO2 desaturations
      occurred during brief central apneas or hypopneas, mainly during REM sleep, the
      apnoea hypopnea index being within normal limits in all cases. The data suggest
      that nocturnal polysomnography can detect otherwise clinically silent hypoxemia
      in SMA patients without any predisposing factor to sleep-disordered breathing
      other than their illness and still showing normal blood-gas tensions during
      wakefulness. Further studies are needed to determine the long-term evolution and
      the prognostic significance of nocturnal hypoxemia in these patients.

PMID- 8282530
TI  - Ischemic stroke and atrial fibrillation. A clinical study.
AB  - In view of the higher prevalence of severe ischemic stroke among patients with
      atrial fibrillation (AF) and of the recently reported higher frequency of stroke
      with AF in females, 516 consecutive patients with ischemic stroke, of whom 93 had
      AF, were retrospectively evaluated. The main anamnestic, clinical and laboratory
      features of the AF and non-AF groups were statistically compared and the features
      of the AF group were statistically evaluated according to gender and age. Our
      results confirm the greater severity of stroke in AF patients than in non-AF
      patients and the higher frequency of stroke with AF in female patients. Moreover,
      a significantly higher frequency of stroke with AF was found in the male 60-69
      and the female 80-89 age groups than in the other age groups. Relevant risk
      factors in females aged 80-89 were hypertension and left ventricular hypertrophy
      (LVH), while diabetes, alcohol, smoking and LVH prevailed among 60-69 year old
      males.

PMID- 8282531
TI  - Acute third cranial nerve ophthalmoplegia: possible pathogenesis from alpha-II
      interferon treatment.
AB  - We report the case of a 67 year old man with acute ophthalmoplegia due to
      extensive damage to the fibers innervating the extrinsic muscles of the left
      third cranial nerve. The condition was secondary to protracted treatment with
      alpha-II-interferon for a HCV virus chronic active hepatopathy.

PMID- 8282532
TI  - Brain reactivity and event--related potentials (ERPs) in patients with sleeping
      sickness.

PMID- 8282533
TI  - Charcot-Marie-tooth syndrome associated with cerebello-extrapyramidal
      manifestations in a patient with tomaculous neuropathy.

PMID- 8282534
TI  - Direct effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on responses to
      lipopolysaccharide (LPS) by isolated murine B-cells.
AB  - Previous results from this laboratory have indicated that the B-cell is the
      primary cell target responsible for the suppression of humoral immunity by
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While other laboratories have
      confirmed that the B-cell is affected, there is not a clear understanding of
      TCDD's relative effects on B-cell proliferation and differentiation. In the
      present study, we isolated B-cells from whole spleen cell suspensions from female
      B6C3F1 mice and further separated them according to density on a percoll density
      step gradient. Cell cycle analysis by propidium iodide indicated that both high
      (i.e., 1.092-1.079 density interface) and low (i.e., 1.079-1.070 density
      interface) density B-cells were predominantly cells in the G0/G1 phase of the
      cell cycle. Based on acridine orange staining, low-density B-cells exhibited
      slightly higher RNA levels than high-density B-cells indicating they are an
      "activated" population of cells, probably somewhere in G1A. Confirmation of these
      results was the observation that the high density, small, resting B-cells had
      negligible background proliferation and immunoglobulin secretion, while the low
      density, larger, activated B-cells had marked background proliferative and
      antibody responses. Direct addition of TCDD (0.3-30.0 nM) produced a significant,
      dose-related and comparable suppression of both parameters in the low density B
      cells. Similar results were obtained when low density B-cells were stimulated
      with LPS and exposed to TCDD. In contrast, neither the proliferation nor the
      antibody response by high density B-cells stimulated with LPS were affected by
      TCDD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282535
TI  - Formation of DNA strand breaks by D-penicillamine and bucillamine in human
      lymphocytes.
AB  - DNA strand breakage by D-penicillamine and bucillamine, anti-rheumatic agents
      with thiol residues was evaluated in DNA unwinding assays. When incubating human
      peripheral blood lymphocytes with D-penicillamine or bucillamine in the presence
      of 8 microM CuSO4, numerous DNA strand breaks occurred and those depended on the
      production of hydrogen peroxide and were completely blocked in the presence of
      catalase. This phenomenon was reversible, and fragmented DNA was repaired in 8 to
      24 h. Significant decreases in cellular NAD levels were observed at
      concentrations of D-penicillamine or bucillamine which could damage DNA. As
      extensive depletion of cellular NAD functionally inactivates lymphocytes, the
      formation of DNA strand breaks may have a role in the immunomodulating action of
      these anti-rheumatic drugs.

PMID- 8282536
TI  - High concentrations of interleukin-2 selectively suppress T-cell dependent
      humoral immune responses.
AB  - The recent therapeutic application of immunoregulatory cytokines, most notably
      the T-cell growth factor, interleukin-2 (IL-2), marks the advent of a new class
      of pharmacologic agents. In the present studies the effects of exogenous IL-2 on
      in vitro humoral immune responses in spleen cells isolated from female B6C3F1
      mice were investigated. In vitro direct addition of low concentrations of rmIL-2
      (25 U/ml) to naive spleen cells induced a moderate enhancement of the T-cell
      dependent antibody forming cell (AFC) response to sRBC. Similarly, low
      concentrations of rmIL-2 (10-50 U/ml) enhanced T-cell independent AFC responses
      to DNP-Ficoll and LPS. Interestingly, high concentrations of rmIL-2 (100 or 250
      U/ml) selectively suppressed the T-cell dependent AFC response but not T-cell
      independent AFC responses to either DNP-Ficoll or LPS. Neither immunoenhancing
      (25 U/ml) nor immunosuppressive (200 U/ml) concentrations of rmIL-2 altered the
      kinetics of the sRBC response. Temporal addition studies indicated that high
      concentrations of rmIL-2 (200 U/ml) were only inhibitory when added to the
      cultures during the first 24 h following antigen sensitization. Conversely, a
      significant enhancement of the response was observed when 200 U/ml rmIL-2 was
      added 48 h following antigen sensitization. These results are in agreement with
      previous reports that the presence of high concentrations of IL-2 render T-cells
      unresponsive to subsequent antigen stimulation but that the high concentrations
      of IL-2 enhance immune responses when added at 48 h following antigen
      sensitization.

PMID- 8282537
TI  - Delta 9-tetrahydrocannabinol selectively inhibits T-cell dependent humoral immune
      responses through direct inhibition of accessory T-cell function.
AB  - The major psychoactive and immunosuppressive component of marihuana, delta 9
      tetrahydrocannabinol (delta 9-THC), was investigated for its effects on primary
      humoral immune responses in the B6C3F1 mouse strain. Oral administration of 50
      200 mg/kg delta 9-THC produced a selective and dose related inhibition of primary
      humoral immune responses to the T-cell dependent antigen, sRBC, as measured by
      the antibody forming cell (AFC) response with no inhibitory effect on humoral
      responses to the T-cell independent antigen, DNP-Ficoll. A similar profile of
      immune inhibition was observed following in vitro direct addition of delta 9-THC
      to naive spleen cell cultures sensitized with defined antigens. delta 9-THC
      produced a marked and dose related inhibition of the in vitro sRBC AFC response
      while having no inhibitory effects on T-cell independent responses to either DNP
      Ficoll or the polyclonal B-cell activator, lipopolysaccharide. This selective
      inhibition of the sRBC response was not due to a shift in the peak day of
      response or a direct cytotoxic effect on spleen cells. In vivo kinetic studies
      demonstrated that inhibition by delta 9-THC of the sRBC response was most
      pronounced when drug administration occurred at times surrounding antigen
      sensitization. To further evaluate the direct effect of delta 9-THC on T-cell
      function, T-cell proliferative responses to stimulation by anti-CD3 monoclonal
      antibodies were measured. delta 9-THC was found to produce a marked and dose
      related inhibition of anti-CD3 mAb-induced T-cell proliferation which was cell
      density dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282538
TI  - Activation of peritoneal macrophages by polysaccharopeptide from the mushroom,
      Coriolus versicolor.
AB  - Polysaccharopeptide (PSP) is a substance produced by an edible mushroom, Coriolus
      versicolor which has been claimed to possess antitumor activity. However, neither
      tumoricidal activity nor cytotoxicity was observed when five tumor cell lines and
      mouse peritoneal macrophages were cultured in vitro in the presence of 2.5-10
      micrograms/ml PSP. An increase in the production of reactive nitrogen
      intermediates, reactive oxygen intermediates (superoxide anions) and tumor
      necrosis factor was measured in peritoneal macrophages collected from inbred C57
      mice which had received PSP in the drinking water for 2 weeks. Northern blot
      analysis also demonstrated that PSP activated the transcription of tumor necrosis
      factor gene in these cells, indicating that PSP exerted an immunomodulatory
      effect on the defensive cells.

PMID- 8282539
TI  - Modulation of TNF-mediated cell lysis in vitro: further analysis of intracellular
      signaling.
AB  - We have investigated the post-receptor events governing the Tumor Necrosis Factor
      (TNF)-mediated cytotoxicity in vitro. As calcium has been reported to be an
      essential mediator in the cell killing processes, we asked whether an early
      increase in intracellular calcium could be involved during TNF-induced cell
      death. Using the ACAS methodology (adherent cell analysis and sorting), we could
      not detect any significant increase in intracellular calcium following TNF
      treatment (40 s) within the TNF-sensitive human breast carcinoma MCF7 cell line.
      In addition, A23187 (0.1-0.4 microM) did neither enhance TNF-mediated MCF7 cell
      lysis, further confirming that TNF-mediated cell lysis can occur in the absence
      of an early calcium increase. Given the potentiating effect of cAMP-inducing
      agents, such as forskolin, on TNF-mediated cytotoxicity, we have investigated the
      relationship between cAMP accumulation and the TNF signaling pathway during cell
      death. Our results indicate that the potentiating effect of forskolin (50 microM)
      on TNF-mediated MCF7 cell lysis did not involve a modulation in the TNF-induced
      activation of the nuclear factor NF-kB but was associated with an increase in the
      DNA fragmenting capacity of TNF as assessed by agarose gel electrophoresis of
      target cell DNA.

PMID- 8282540
TI  - Control of IgE responses. II. Isotype specific suppression of peak hapten
      specific IgE antibody forming cell responses in BPO-KLH sensitized mice after
      oral administration of muramyldipeptide or murabutide.
AB  - Muramyldipeptide (MDP) and murabutide (MB), a pyrogen free derivative of MDP,
      suppressed BPO specific IgE antibody forming cell (AFC) responses in vivo. To
      induce IgE responses, BALB/c mice were injected intraperitoneally (i.p.) with BPO
      KLH (10 micrograms) in alum on days 0 and 21, or on days 0, 21 and 42. On day 44,
      mice were fed (gavage) or injected subcutaneously (s.c.) with MDP or MB (0.1-500
      mg/kg). Mice were killed on days 45-70, and the numbers of BPO specific IgM,
      IgG1, IgE, and IgA antibody forming cells (AFC) in lymphoid organs determined in
      ELISPOT assay. With either immunization schedule, oral treatment with MDP or MB
      on day 44 suppressed BPO specific IgE AFC responses within 48 h (65-100%). With
      both molecules, the suppression was IgE isotype specific, dose dependent and
      transient. The suppression was also route specific since it was obtained only
      when MDP or MB was given by gavage, and not when injected s.c. These results show
      that peak antigen specific IgE responses can be suppressed in vivo, in isotype
      specific fashion, by a clearly defined class of molecules, one of which, MB, is a
      candidate for clinical studies in man. Pharmacologic agents of this type may be
      suitable for use in the therapeutic or prophylactic suppression of IgE and,
      hence, in the therapy of IgE mediated diseases such as allergic rhinitis, asthma,
      and other atopic diseases.

PMID- 8282541
TI  - Thymosin stimulates interleukin-6 production from rat spleen cells in vitro.
AB  - Thymosin fraction 5 (TF5) is a partially purified preparation of bovine thymus
      that affects the differentiation and function of T-cells in vitro. Interleukin-6
      (IL-6) is a pleiotropic cytokine that induces terminal maturation of B-cells and
      T-cell activation and differentiation. Although TF5 had previously been shown to
      stimulate the production of a number of lymphokines, its effects on IL-6 were not
      known. In this study we determined the effect of TF5 on IL-6 production from rat
      spleen cells in vitro. TF5 (100 micrograms/ml) stimulated IL-6 production from
      splenocytes (0.75-3.0 x 10(5) cells/well) in the presence of 0.008-0.2
      micrograms/well of the T-cell mitogen concanavalin-A (con-A) by 10-20 fold during
      a 72 h incubation period. Dose-response studies demonstrated that 10
      micrograms/ml of TF5 was the lowest concentration capable of enhancing IL-6
      production. The ability of TF5 to stimulate IL-6 production in the presence of
      con-A could be demonstrated within 24 h of incubation; longer incubation periods
      (48-72 h) correlated with further enhancements of IL-6 production. Partial
      purification of the IL-6-inducing activity from TF5 resulted in three
      subfractions possessing activity in the presence of con-A (MB2, MB3, MB7) and one
      in the absence of con-A (MB2). The previously characterized thymosin peptides T
      alpha 1 and T beta 4 had no effect on IL-6 production in the absence or presence
      of mitogen. This study reports a new biological activity for TF5 and suggests
      that a novel constituent of TF5 may enhance the production of IL-6 from spleen
      cells.

PMID- 8282542
TI  - CTX-B inhibits CTL cytotoxicity and cytoskeletal movements.
AB  - Binding of cytotoxic T lymphocytes (CTL) to specific targets induces cytoskeletal
      movements in the effector cell followed by delivery of the lethal hit which
      ultimately results in target cell lysis. The question whether movement of the
      cytoskeleton in CTL are obligatory for delivery of the lethal hit is not
      resolved. Here we report that the CTX-B subunit of cholera toxin which is devoid
      of the catalytic CTX-A subunit inhibits CTL function. Inhibition was found not to
      be due to interference with TCR expression, CTL-target conjugate formation,
      target induced transmembrane signalling or secretion of BLT-esterase. CTX-B
      however does interfere with F-actin patch formation at the effector target
      binding site and inhibits reorientation of the microtubule organizing center and
      Golgi apparatus towards the target binding site. It is concluded that
      interference with cytoskeletal movements is responsible for inhibition of
      cytolysis pointing to an important role of the cytoskeleton in the lytic
      reaction.

PMID- 8282543
TI  - Board training policies and practices.
AB  - This survey reveals some very interesting aspects about training of hospital
      boards of directors. When both CEOs and board chairpersons agree that making
      board training mandatory is necessary today, it is probably worthy of some
      serious board discussion.

PMID- 8282544
TI  - Spreading the "good news" of total quality management: faith, conversion, and
      commitment.
AB  - In many ways the spread of total quality management (TQM) across this country can
      be compared to a religious conversion. Both cases are characterized by a
      philosophical shift with far-reaching changes in responsibilities and incentives
      for the people involved. This article bridges the disciplines of theology and
      health services management by elaborating a metaphor in which TQM is compared to
      various aspects of the Judeo-Christian faiths, such as the role of laws and
      standards; the importance of miracles, prophets, and evangelists; and the
      practical applications of living out the faith.

PMID- 8282545
TI  - Optimizing the delivery of patient and physician satisfaction: a conjoint
      analysis approach.
AB  - This article suggests that, in evaluating and designing health care unit
      programs, conjoint analysis is superior to the conventional survey-research
      approach. Conjoint analysis can suggest unit designs that will optimize patient
      (or physician) satisfaction, while still controlling for unit profitability and
      other constraints. This article discusses the conjoint approach and illustrates
      its use in the design of an obstetrical unit.

PMID- 8282546
TI  - American business ethics and health care costs.
AB  - The health care industry operates in the margin between market competition and
      social welfare programs. Violations of business ethics on the market side add
      considerably to costs. When the inefficient use of resources and market
      distortions due to power and ignorance as well as legal and subsidized monopolies
      are added, increased costs can approach $100 billion. Modest remedies are
      suggested.

PMID- 8282547
TI  - The proliferation of health care contracts at a tertiary care hospital:
      organizational and financial impacts.
AB  - The impact of negotiation and management of numerous health insurance contracts
      on one tertiary care hospital's organization and costs is explored. Contract
      related activities have proliferated within the organization, requiring extensive
      labor time and costs. Information exchange is the most time-consuming activity,
      suggesting that systems are needed both to facilitate transmission of information
      among hospital personnel, insurers, physicians, and review organizations and to
      reduce the variation among contracts.

PMID- 8282548
TI  - Physician-hospital conflict among salaried physicians.
AB  - Physicians who were full-time salaried employees in nonprofit hospitals
      experienced conflict between their medical-clinical considerations and the
      administrative constraints imposed by the hospital. The level of experienced
      conflict was mostly related to the physicians' commitment to the hospital, the
      realization in the hospital of their work expectations, and external political
      influences exerted on the hospital. The implications of the findings for the
      physicians under a highly controlled work setting are discussed.

PMID- 8282549
TI  - Trends and models in physician-hospital organization.
AB  - Physicians and hospitals have developed new models for aligning their incentives
      and integrating their activities. These models serve numerous purposes, including
      unified contracting with managed care organizations, improved access to capital
      and patients, and strengthened competitive position. The more advanced models
      carry the added potential of providing comprehensive, community-based care with
      less duplication of services. The new models raise several important issues that
      providers need to consider before embarking on these strategies.

PMID- 8282550
TI  - Organizational characteristics and administrative strategies associated with
      staff turnover.
AB  - In a study at 55 hemodialysis facilities, turnover was not associated with
      organizational size, location, or ownership but varied according to
      administrative strategies. Technician turnover (32 percent) was lower in
      facilities with shorter hours and choice of work schedule even though workload
      was higher. Clerical turnover (36 percent) was reduced with lower workloads.
      Nursing turnover (31 percent) was reduced in facilities in operation longer with
      shorter hours but equivalent workloads. Administrative turnover was negligible.

PMID- 8282551
TI  - A study of substance abuse testing in patient care facilities.
AB  - Drug testing, once practically ignored as a health care management strategy in
      curbing legal liability potential, is now the norm rather than exception. Most
      hospitals today conduct drug tests involving employment considerations and "for
      cause" (e.g., accidents) involving most employees but excluding physicians.
      Random drug testing is recommended for health care institutions to consider as a
      strategy designed to reduce illicit drug abuse in such facilities. This
      recommendation is based on the nature and sensitivity of the health care
      institution's mission and purpose relative to patient care and safety.

PMID- 8282552
TI  - The question of health effects from exposure to electromagnetic fields.
AB  - Possible health effects of exposure to low-intensity electric and magnetic fields
      (EMFs) are receiving increased attention in the scientific literature and,
      especially, in the public media. Laboratory research at the cellular and whole
      animal level has demonstrated various biological effects that may be related in
      some manner to the effect of EMF exposure on people. However, the exact
      mechanisms of this relationship are far from clear. The studies suggest that EMFs
      might be cancer promoters but are unlikely to be cancer initiators. At the level
      of human epidemiology, approximately 50 studies have examined the possible
      correlation of EMF exposures with adult and childhood cancers. Although the
      possibility of a correlation is weak, it cannot be discounted, and further
      research is needed. In the meantime, a practice of "prudent avoidance" of
      prolonged exposure to EMFs is warranted.

PMID- 8282553
TI  - Thyroid doses resulting from the Ukraine Chernobyl accident--Part I: Dose
      estimates for the population of Kiev.
AB  - In the context of the radiation exposure of the Ukrainian population resulting
      from the Chernobyl accident, the quantification of the thyroid doses due to
      iodine incorporation is of special interest. This first part of a series of
      planned publications deals with the dose and risk estimation for Kiev citizens.
      Although these doses are expected to be considerably lower than those for some
      other regions of Ukraine, the investigations started with this population because
      the quantification of the thyroid doses due to iodine incorporation is of special
      interest. This first part of a series of planned publications deals with the dose
      and risk estimation for Kiev citizens. Although these doses are expected to be
      considerably lower than those for some other regions of Ukraine, the
      investigations started with this population because of the availability of rather
      reliable measurements and because of the size of this population. The methods
      developed allowed the estimation of individual thyroid doses. The average values
      of individual thyroid doses for five age groups (birth years 1983-1986, 1979
      1982, 1975-1978, 1971-1974, and < 1971) are 104, 62, 19, 18, and 41 mGy,
      respectively. The collective thyroid doses were estimated as 83 x 10(3) person-Gy
      for those born before 1971 and as 38 x 10(3) person-Gy for younger inhabitants.
      The numbers of expected thyroid cancers in the whole Kiev population are 66 and
      130, respectively.

PMID- 8282554
TI  - Field test of electret ion chambers for environmental monitoring.
AB  - A field test of electret ion chambers was performed to evaluate their performance
      in making environmental exposure measurements at nuclear facilities. The
      objectives of the study were to determine electret ion chamber variability and to
      perform comparisons with thermoluminescent dosimeter and high-pressure ion
      chamber measurements. Three electret ion chambers were placed at each of 40
      monitoring locations in the vicinity of a commercial nuclear power station during
      four consecutive quarters. The electret ion chamber measurements were compared to
      thermoluminescent dosimeter measurements made by the Nuclear Regulatory
      Commission and the South Carolina Department of Health and Environmental Control.
      Two types of comparison were made with the high-pressure ion chamber. One used
      yearly average electret ion chamber measurement and instantaneous high-pressure
      ion chamber measurements at 15 of the monitoring locations. The other involved
      the simultaneous exposure of five electret ion chambers and the high-pressure ion
      chamber for 15 d at a single location. The mean ratios of electret ion chamber
      measurements to thermoluminescent dosimeter measurements was 1.06. The mean ratio
      of electret ion chamber measurements to instantaneous and simultaneous high
      pressure ion chamber measurements were 1.06 and 1.07, respectively. Electret
      variability, defined here as the ratio of the standard deviation to the mean, was
      determined for each set of three detectors. The average variability for the 160
      sets of quarterly measurements was approximately 7%. Among the 450 individual
      electret measurements, there were six outliers. Based on the results of this
      study, electret ion chambers appear to yield accurate measurements of
      environmental exposure provided that measures are taken to either minimize or
      correct for radon interferences and care is taken to prevent spurious discharges
      during handling.

PMID- 8282555
TI  - Application of the Moyer method to transverse shielding of a linear
      bremsstrahlung source.
AB  - The Moyer method is applied to the design of transverse shielding for an electron
      linear accelerator, assuming uniform beam power loss along the accelerator
      structure. The limitations of the method with respect to primary beam energy are
      discussed. Only the component of the radiation field due to bremsstrahlung is
      considered in this paper. Parameters for this application are given and sample
      calculations are shown. For a beam power loss uniformly distributed with distance
      along a straight line of 0.5 W m-1, it is predicted that 1.2 m of concrete are
      needed to reduce the dose equivalent rate to 50 muSv h-1 (1.39 x 10(-8) Sv s-1),
      at a transverse distance of 3.5 m from the source.

PMID- 8282556
TI  - Image jitter, blur, and scintillation regarding the retinal hazards of lasers.
AB  - The statistics of position and size of the image of a laser source observed
      through refractive turbulence in the atmosphere were measured using a simulated
      human retina. Both 3-mm and 7-mm apertures were used with a variety of
      propagation conditions. No significant effects of image broadening or motion were
      observed. Consequently, such effects cannot be depended on to mitigate
      scintillation hazards.

PMID- 8282557
TI  - A performance evaluation of bare alpha track detectors.
AB  - Bare alpha track detectors are sensitive to radon progeny as well as to radon
      gas. This paper reports the test results for two brands of bare alpha track
      detectors that received several radon exposures at three progeny concentrations.
      The results show a relationship that is a linear combination of both the radon
      gas and the radon progeny concentrations. The reported radon concentration
      depended on the equilibrium factor assumed by the processor. The sensitivity of
      bare alpha track detectors increases with altitude, but this is a minor,
      correctable effect compared to the equilibrium factor.

PMID- 8282558
TI  - Skeletal malignancies among beagles injected with 241Am.
AB  - Seventy skeletal malignancies in 44 dogs were identified among 117 beagles
      injected as young adults with graded dosages of approximately 0.07 to 104 kBq
      241Am kg-1 and maintained for lifetime observation. All of these tumors were
      osteosarcomas except four fibrosarcomas of bone and four chondrosarcomas of bone.
      Of these 117 animals, 114 survived beyond the minimum age (of 2.79 y) for
      radiation-induced bone cancer, and all are now dead. An expression was derived
      that described the dependence of percent occurrence of bone sarcoma on skeletal
      radiation dose of A = 0.76 + 30D, where A = percent of dogs with skeletal
      malignancy within any dosage group, D = average skeletal dose (< 3 Gy) at 1 y
      before death (average skeletal dose was calculated to the presumed start of tumor
      growth, which we have taken to be 1 y before death), and 0.76 represents the
      lifetime percent malignant bone tumor response among 132 suitable control dogs in
      our colony not given any radioactivity. All dosage groups with skeletal doses of
      > 3 Gy at 1 y before death exhibited close to 100% occurrence and appeared to be
      beyond the region of linearity. Therefore, they were excluded from the derivation
      of this expression. Similar analysis of corresponding data for beagles given
      226Ra as young adults, excluding the two highest dosage groups in which the bone
      tumor response was approximately 100%, yielded the expression, A = 0.76 + 4.7D,
      (D < 20 Gy). A ratio of the coefficients in these two expressions indicates the
      effectiveness at low radiation doses for bone-cancer induction of 241Am relative
      to 226Ra, or (30 +/- 2.6)(4.7 +/- 0.47)-1 = 6 +/- 0.8. This compares to the
      relative effectiveness at low radiation doses that was obtained earlier for a
      239Pu:226Ra toxicity ratio of about 16 +/- 5.

PMID- 8282559
TI  - The use of computed radon entry rates to understand radon concentration in
      buildings.
AB  - The central role played by basement depressurization in drawing radon
      contaminated soil gas into a structure has been demonstrated by calculating the
      radon entry rate from radon concentration and air infiltration measurements at
      different levels of basement depressurization in a single-family research house.
      The radon entry rate is found to be a linear function of basement
      depressurization in this house which indicates that the flow of soil gas into the
      structure is laminar. The radon entry rates calculated before and after using a
      mitigation procedure is shown to provide a better measure of the mitigation
      efficacy than the standard before and after mitigation radon measurements in a
      research house. In addition, an analysis of the possible flow characteristics of
      soil gas and uncontaminated air into a basement indicates that any attempt to
      predict long-term average radon exposure from short-term screening measurements
      will only be possible under severely restricted conditions.

PMID- 8282560
TI  - Summer outdoor radon variations in Canada and their relation to soil moisture.
AB  - In the summers of 1990 and 1991, outdoor 222Rn detectors were installed for 3 mo
      in 78 communities across Canada. The 1990 measurements showed large regional
      variations with the average outdoor levels for the provinces of Manitoba (59 Bq m
      3) and Saskatchewan (61 Bq m-3) exceeding the average indoor levels of 55 Bq m-3
      for the U.S. The variations in the 1990 222Rn levels showed little correlation
      with the uranium concentration of the ground and were attributed to changes in
      soil moisture content. All measurements above 30 Bq m-3 were found to be in dry
      climatic regions where the annual precipitation was less than 550 mm. In
      addition, most of the sites with high 222Rn levels were on glacial lake clays. A
      soil moisture modeling program showed that because of the low precipitation,
      these clays were drying out in the summer allowing fractures to develop and 222Rn
      to migrate easily through the ground. The much lower 1991 measurements for
      Manitoba (10 Bq m-3) and Saskatchewan (15 Bq m-3) were believed to be due to the
      increased precipitation in the prairie regions in the summer of 1991 compared to
      the unusually dry summer of 1990.

PMID- 8282561
TI  - Natural radioactivity in Spanish soils.
AB  - The program of studies and surveys of natural radiation and radioactivity in
      Spain organized by our research group at the end of the 1980s included a 4-y
      national survey to determine the concentrations of natural radionuclides in soil.
      Results obtained from measurements of soil samples collected nationwide at > 900
      sampling sites are reported and discussed in this paper. Correlations between
      absorbed dose rates in air calculated from natural radionuclide concentrations in
      soil and terrestrial gamma dose rates measured experimentally outdoors are shown
      for the different autonomous regions of Spain. Assessment is also made of the
      dose to the Spanish population from outdoor exposure to terrestrial gamma rays.

PMID- 8282562
TI  - Indoor radon maps of the United States.
AB  - A recently published compilation of average radon levels in 1,729 U.S. counties
      with standard errors of approximately 20% is used to generate maps exhibiting
      these results and showing correlations over multicounty areas. Several large
      areas and numerous smaller areas with high radon levels are identified.

PMID- 8282563
TI  - Missing dose from mortality studies of radiation effects among workers at Oak
      Ridge National Laboratory.
AB  - Missing dose is a problem that has not been adequately addressed in the mortality
      studies of radiation effects among workers at Oak Ridge National Laboratory. The
      missing dose is a result of recording a zero for below-detectable doses,
      especially for frequent (weekly) film badge readings. To make the thorough
      dosimetry assessment needed in the current Oak Ridge National Laboratory worker
      studies, it will probably be necessary to consider all data at hand including
      personnel dose records, daily pocket meter readings used to supplement weekly and
      quarterly readings from other dosimeters, and monitoring results from both
      building surveys and fixed stations. The fixed-station data should be extremely
      useful in developing a better understanding of the unusual temporal variation of
      the external radiation doses to Oak Ridge National Laboratory workers during the
      high exposure-rate periods of the 1950s and early 1960s.

PMID- 8282564
TI  - Potential for radioactive patient excreta in hospital trash and medical waste.
AB  - Radioactive excreta from nuclear medicine patients can enter solid waste as
      common trash and medical biohazardous waste. Many landfills and transfer stations
      now survey these waste streams with scintillation detectors which may result in
      rejection of a hospital's waste. Our survey indicated that on the average either
      or both of Boston University Medical Center Hospital's waste streams can contain
      detectable radioactive excreta on a weekly basis. To avoid potential problems,
      radiation detectors were installed in areas where housekeepers carting trash and
      medical waste must pass through to ensure no radioactivity leaves the
      institution.

PMID- 8282565
TI  - Reply to Stidley and Samet.

PMID- 8282567
TI  - Histochemical analysis of rat testicular glycoconjugates. 3. Non-reducing
      terminal residues in seminiferous tubules.
AB  - Lectins of Helix pomatia (HPA), Glycine max (SBA), Vicia villosa (VVA), Dolichos
      biflorus (DBA), Ulex europaeus (UEA-1), Tetragonolobus purpureus (LTA), Griffonia
      simplicifolia (BSA-1B4), Maclura pomifera (MPA), Sambucus nigra (SNA) and Maackia
      amurensis (MAA) were used to explore the distribution of saccharides
      characteristic of non-reducing termini of O- and N-linked glycoprotein glycans in
      the seminiferous tubules of rat testis. Sialyl residues (both alpha 2,3- and
      alpha 2,6-linked, as shown by MAA and SNA respectively) and alpha-L-fucosyl
      residues (shown by UEA-1 and LTA) were expressed on spermatogonia, spermatocytes
      and spermatozoa, but not on spermatids. In contrast, 2-deoxy-2-acetamido-alpha-D
      galactosyl termini were abundant on spermatozoa, but not on any of their
      precursors (as shown by HPA, SBA and VVA). All occurred on both O- and N-linked
      glycans. Sertoli cells expressed small amounts of fucose and alpha 2,3-linked
      sialic acid, and abundant alpha 2,6 sialyl residues, largely on N-glycans. alpha
      Galactosyl residues were readily detected on the tubular basement membrane, but
      not elsewhere.

PMID- 8282566
TI  - Cellular sialoglycoconjugates: a histochemical perspective.
AB  - Sialic acids are found at the non-reducing terminus of oligosaccharide side
      chains of most glycoproteins and glycolipids. Their expression is often
      developmentally regulated during organogenesis and in differentiating cells.
      Further, differential expression of various sialyltransferases results in organ-
      and cell-type specific expression of sialylated glycosylation sequences. The
      availability of highly specific lectins and of monoclonal antibodies has
      permitted histochemical investigations of the various cellular and subcellular
      aspects of the process of sialylation. This review provides a survey on the
      developmentally regulated and organ- as well as cell-type specific expression of
      various sialoglycoconjugates and their tumour-associated occurrence with special
      reference to intestine and kidney.

PMID- 8282568
TI  - Distribution of saccharides in pig lymph-node high-endothelial venules and
      associated lymphocytes visualized using fluorescent lectins and confocal
      microscopy.
AB  - The distribution of saccharides in pig lymph nodes, particularly on high
      endothelial venule (HEV) endothelium and on lymphocytes in these vessels, was
      studied by examining the binding of fluorescent conjugates of 18 different
      lectins. Eight of the lectins, particularly with glycan specificity restricted to
      mannose and polyacetyllactosamine determinants, were found to bind with a high
      affinity to these structures. Competitive inhibition experiments revealed that
      polylactosamine-containing glycans were present on endothelia and lymphocytes
      using lectins from Lycopersicon esculentum and Solanum tuberosum, the latter
      lectin reacting with lymphocytes only when apparently adherent to the luminal
      endothelium. The The absence on pig endothelium of the Ulex europaeus binding,
      shown by human endothelia due to the presence of certain fucose epitopes, was
      confirmed. Pig lymph-node endothelium, however, bound the fucose-specific lectin
      of Tetragonolobus purpureas, indicating the presence of fucose on pig endothelia
      in a different conformation to that seen on human endothelia. The results
      suggested that pig lymph-node HEV endothelium expressed a core fucosylated tri-
      or tetra-antennary complex glycan with polylactosamine extensions and expressing
      an Ley determinant.

PMID- 8282569
TI  - Methodological aspects on immunohistochemistry in dermatology with special
      reference to neuronal markers.
AB  - In an attempt to optimize the immunohistochemical procedure for visualizing
      neuronal markers, such as neuropeptides, in the human skin, different
      alternatives in all steps of the process were compared. We have studied the
      influence of type of immunohistochemical method, the biopsy technique, including
      the size of the punch biopsy, anaesthesia, the choice of fixative and the time of
      fixation, the storage process, the sectioning parameters, incubation procedure,
      the type of fluorophore-conjugated antibody and its dilution, mounting and
      storage, and, finally, microscopical examination. The following procedure was
      found to give the best result: punch biopsies of 3 mm, taken under local
      anaesthesia using lidocaine injected into the dermis-subcutis at the place of
      biopsy; fixation by a buffered 10% formalin solution containing 14% of saturated
      picric acid for 2 h at 4 degrees C; storage in 10% sucrose buffer for at least 24
      h up to 1 month at 4 degrees C or deep-frozen to -70 degrees C for 2 months (with
      only a minor structural deterioration); cryostat sectioning of the biopsies with
      a section thickness of 14 microns and with the cutting edge perpendicular to the
      skin surface; rhodamine (TRITC)-conjugated, instead of fluorescein-isothiocyanate
      (FITC)-conjugated, secondary antiserum, since it gives a lower background
      fluorescence; and for the incubation and mounting procedures, our standard
      laboratory routines were applied. The result is an optimal indirect
      immunofluorescence technique, to be applied in dermatology. We also found that
      biopsies taken under local anaesthesia with chloroethyl spray lost almost all
      immunofluorescence for several neuronal markers in the epidermis-upper dermis.

PMID- 8282570
TI  - Renal immunolocalization of kallikrein in cisplatin nephrotoxicity in rats.
AB  - Treatment of rats with cisplatin (4 mg kg-1 body wt i.p. injection) induced
      variations of urinary kallikrein excretion (UKE). Three phases were observed: a
      transient increase of UKE one day after injection, followed by a decrease up to
      10 days suggesting an altered biosynthesis and a recovery phase with return to
      normal control values, 21 days after injection. Early morphological lesions were
      observed in proximal tubule cells on day 1; severe changes and tubular necrosis
      were observed in the following days. Less marked changes were also present in
      distal tubules but the vacuolated and desquamated cells appeared in the lumen of
      the tubules. By immunocytochemical methods, kallikrein was observed in connecting
      tubule cells, but also in some proximal tubule cells and along the endothelial
      side of the glomerular basement membrane and urinary space of glomeruli. An
      intense labelling was present in desquamated epithelial cells in dilated lumen of
      tubules. This study provides evidence of the presence of immunoreactive
      kallikrein in the glomerulus, already reported during acute failure, and confirms
      the use of urinary kallikrein measurements as a useful non-invasive index to
      assess a possible nephrotoxic effect at the distal level.

PMID- 8282571
TI  - [Minitracheotomy and percutaneous tracheotomy. Tracheotomy today].

PMID- 8282573
TI  - [Photodynamic laser therapy. Head and neck cancers].

PMID- 8282572
TI  - [Otosclerosis. An autoimmune disease?].

PMID- 8282574
TI  - [Cartilage-specific autoimmunity in otosclerosis].
AB  - The otic capsule of patients with otosclerosis contains premature bone with
      numerous cartilaginous remnants. Some investigators have proposed that the
      pathogenesis of otosclerosis is related to these cartilaginous rests in the otic
      capsule. In this study we investigated the presence of a humoral immune reaction
      against cartilage-specific antigens using ELISA-methods in patients with
      otosclerosis. Concomitantly, 8 age- and sex-matched healthy blood donors, free of
      any symptoms of autoimmune disease, served as controls. The following antigen
      substrates were used: collagen (I, II, III, VI, IX and XI), chondrocytes and
      chondrocyte membranes. Findings then showed that the levels of antibodies to
      collagens type II and IX as well as to chondrocytes were higher in the
      otosclerosis patients than in the control subjects. The high titer of antibodies
      against chondrocytes was not accompanied by an increase in antibodies against the
      chondrocyte membranes. To our knowledge these observations represent the first
      evidence for the existence of autoantibodies against minor collagens and
      chondrocyte-specific antigens and support a possible role for a cartilage
      specific autoimmunity in the etiopathogenesis of otosclerosis.

PMID- 8282575
TI  - [The Wittmaack temporal bone collection and possibilities for cataloguing with
      electronic data processing].
AB  - Karl Wittmaack, head of the otology department at Greifswald (1904-1908) and
      professor of otorhinolaryngology at the universities of Jena (1908-1925) und
      Hamburg (1926-1946) created a unique histological collection of human and animal
      temporal bones that is thought to be the largest of its kind in the world. The
      serial sections of more than 1700 human temporal bones still represent current
      otological problems--many of which are now rare but are still encountered--such
      as tuberculosis, lues or diphtheria of the ear. Complications following acute
      otitis--which were much more frequent and dangerous in the pre-antibiotic era-
      can be studied in detail. There are numerous cases of labyrinthitis, meningitis,
      sinus thrombosis, brain abscess etc.--complications which must always be borne in
      mind to this day. The same is true for tumors like acoustic neurinomas or even
      malignant tumors, metastases, or manifestations of leukemia. Differences in
      pneumatization or changes of the bone structure as in otosclerosis have been the
      subjects of studies dating from Wittmaack's time until very recently. In spite of
      its topicality, the true value of the collection has only be appreciated by a
      limited group of persons, which may be due in part to difficulties in orientation
      within this vast amount of material. Although there are catalogues, it may be
      difficult to find the appropriate preparations for particular questions.
      Searching for such specimens often requires rummaging through the whole
      collection, sometimes resulting in damage or loss of slides or handwritten
      notes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282576
TI  - [Magnetic resonance tomography and computerized tomography in tumor staging of
      mouth and oropharyngeal cancer].
AB  - 30 patients with malignant tumours of the cavum oris and oropharynx were examined
      by MRI and CT to compare their accuracy for T-staging. There was histological
      information in all cases. Histological studies showed an accuracy in T-staging of
      81% for MRI and 77% for CT. Differentiation between stages T2/T3 and T3/T4 is
      possible in 80% by CT and 84% by MRI. Tumours of the cavum oris and oropharynx of
      T1-stage are possible only in 1 of 3 cases. The use of T2-weighted sequences
      allows the best frequence of tumour representation in 89%. CT shows an earlier
      bone involvement than MRI. In addition, the ability to produce coronal and
      sagittal images by MRI makes it superior to CT in judging tumour extension.

PMID- 8282577
TI  - [Morphology and clinical aspects of paragangliomas in the area of the head-neck].
AB  - Clinical data and tumor specimens from 63 patients were investigated, and
      included 22 glomus caroticum tumors and 41 tumors of the tympano-jugulare region.
      All specimens could be differentiated by their histological growth patterns into
      four categories. The clinical data revealed that 45% of the female patients with
      paragangliomas suffered from goitre, one of whom died in thyrotoxic crisis after
      surgery. Two patients died from sequelae of other serious diseases. In general,
      postoperative morbidity was solely caused by cranial nerve palsies depending on
      tumor extent. From the data presented, a conclusion is drawn that serious
      concurrent diseases are the limiting factor for surgery. Early detection is the
      best way to reduce postoperative morbidity if total removal of the tumor is
      required.

PMID- 8282578
TI  - [Keratoacanthoma of the external ear].
AB  - Six hundred and seventy-eight keratoacanthomas were treated in Hornheide during
      the past 30 years. Nearly 10% (67) were located on the auricles. One patient
      suffered from two tumors. The records of 8 patients were lost. Fifty-two of the
      remaining 59 cases involved males and only 7 patients were female. There was a
      striking difference between the sex incidence of the patients with auricular
      tumors and the overall total of the keratoacanthomas, with a nearly equal
      involvement of both sexes in the latter. The growth time of lesions before
      treatment was mostly defined in weeks or even days. The prevalence increased with
      age and only 2 patients were younger than 50 years. Therapy depended on growth
      stage, tumor diameter and localization. Therapeutic measurements ranged from
      excessive surgical treatment to no treatment. In practise, special dermato
      oncologic experience is necessary for making any decisions concerning the best
      method of treatment.

PMID- 8282579
TI  - [Gasperini syndrome--differential diagnosis of peripheral facial nerve paralysis.
      Neurologic and imaging findings].
AB  - The Gasperini syndrome is a cause of peripheral facial palsy: In the following
      case report, a 75-year-old woman is described who presented with a peripheral
      left facial palsy. On examination left beating nystagmus was found with
      contralateral loss of pain and temperature affecting the right side of the body
      but sparing the face. The signs and symptoms corresponded to the Gasperini
      syndrome caused by a lesion in the dorsal caudal pons in the region of the
      anterior inferior cerebellar artery. MR imaging confirmed a lesion in this site.

PMID- 8282580
TI  - [Cerebral seizure in naftidrofuryl infusion].
AB  - The case of a 7-year-old boy who suffered a convulsion during parenteral infusion
      of naftidrofuryl is reported. The effectiveness of adding naftidrofuryl to
      infusions designed to increase cochlear blood flow in cases of sudden hearing
      loss has been keenly debated in the otologic literature. Several hazards are
      associated with this drug, especially when the infusion is performed too fast. We
      recommend an individual decision for each patient suffering from cochleo
      vestibular disorder based on the neurological and cardiological risk factors and
      the therapeutic possibilities.

PMID- 8282581
TI  - [Immediate management of rupture and soft tissue injuries in the area of the head
      neck].
AB  - Most injuries to the head and neck region are accompanied by trauma to the soft
      tissue. The management of the wound depends on whether it is a superficial or a
      penetrating trauma. Penetrating traumas may injure bloodvessels, nerve structures
      and the upper aerodigestive tract. The initial evaluation of a patient with a
      neck wound should proceed with the basic rules of trauma management (Airway,
      Bleeding, Circulation). It is suggested, that all wounds deep to the platysma
      should be explored. Penetrating injuries through the airway should be considered
      in cases of hoarsness, dyspnea or direct visualization of the airway. In case of
      dyspnoe the patient should be intubated. In an unstable airway a tracheotomy must
      be considered. Injuries to the airway demand special care and immediate
      reconstruction since otherwise it can lead to permanent damage. Hemorrhage and
      hematoma are the most common symptoms of penetrating neck injuries. Poor initial
      control of bleeding is the most common cause of death. Uncontrolled clamping of
      vessels in the neck should be avoided since it can lead to damage of uninvolved
      structures especially nerves. The neck is divided into 3 zones. Zone I is the
      area below the sternal notch, Zone II lies between the sternal notch and the
      angle of the mandible. Zone III is the area above the angle of the mandible. Zone
      I and III injuries are evaluated with angiography. Zone II injuries are evaluated
      by surgery. Therapy of Zone I and III is difficult and needs mandibulotomy or
      resection of the clavicle to gain exposure to the vessels.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8282582
TI  - [Immunohistochemical analysis of cell surface markers in leprosy patients].
AB  - Nine biopsy specimens from 3 tuberculoid (TT), 1 borderline tuberculoid (BT), 2
      borderline (BB), 2 borderline lepromatous (BL), and 1 lepromatous (LL) patients
      were studied using immunoperoxidase procedures with monoclonal antibodies. In TT
      patients 4B4+, TCR alpha beta+, CD4+ T cells were dominant in dermal granulomas.
      In LL patient, dermal granulomas with 4B4+, TCR alpha beta+, CD4+ T cells and
      2H4+, TCR alpha beta+, CD4+ T cells also had CD8+ T cells. The proportion of 4B4+
      T cells increased in granulomas from LL to TT and 2H4+ T cells proportionately
      increased from TT to LL. TCR gamma delta+ T cells were detected only in BB and BL
      patients. However, there is no difference of staining pattern of ICAM-1 or LFA-1
      antigen in any type of leprosy. These results indicate that the
      immunohistochemical pattern of T cells (CD4, CD8, 4B4, 2H4, TCR) may be useful in
      the diagnosis of the spectrum of leprosy.

PMID- 8282583
TI  - Current leprosy situation and control programme in Bangladesh.

PMID- 8282584
TI  - [Detection of MRSA in National Leprosarium of Ohshima Seisho-En].

PMID- 8282585
TI  - [On the establishment of Fukusei Byoin--letter of father Germaine Testevuide,
      founder].

PMID- 8282586
TI  - Invited editorial on "demonstration of pulmonary vascular perfusion by electron
      and light microscopy".

PMID- 8282587
TI  - Hemodynamic changes associated with obstructive sleep apnea followed by arousal
      in a porcine model.
AB  - To study the effects of airway obstruction (AWO) and arousal on coronary blood
      flow, mean arterial pressure (MAP), and heart rate, pigs were chronically
      instrumented with arterial catheters, Doppler flow probes on the left circumflex
      coronary artery, and electrodes for determination of sleep stages. A modified
      tracheostomy tube was placed in the trachea to obstruct the upper airway during
      sleep sessions. In control studies, during non-rapid-eye-movement (NREM) sleep,
      MAP was 84 +/- 2 mmHg before AWO and increased by 5 +/- 2 mmHg on arousal. MAP
      was lower during rapid-eye-movement (REM) sleep (62 +/- 2 mmHg), and the increase
      on arousal was fourfold greater (22 +/- 2 mmHg). Heart rate was similar in both
      sleep stages (NREM: 120 +/- 4 beats/min; REM: 124 +/- 5 beats/min) and increased
      significantly on arousal (NREM: 12 +/- 2 beats/min; REM: 18 +/- 1 beats/min).
      Coronary blood flow was similar during both stages (NREM: 43 +/- 4 ml/min; REM:
      46 +/- 8 ml/min) and increased by 12-15% on arousal. Coronary vascular resistance
      index increased significantly by 24% on arousal from AWO during REM sleep. All
      increases and decreases were significant at P < 0.05. Receptor blockade studies
      were performed to assess alpha-adrenergic receptor involvement.

PMID- 8282588
TI  - Effects of detraining on endurance capacity and metabolic changes during
      prolonged exhaustive exercise.
AB  - The effects of 4 wk of detraining on maximal O2 uptake (VO2max) and on endurance
      capacity defined as the maximal time to exhaustion at 75% of VO2max were studied
      in nine well-trained endurance athletes. Detraining consisted of one short 35-min
      high-intensity bout per week as opposed to the normal 6-10 h/wk. Detraining had
      no effect on VO2max (4.57 +/- 0.10 vs. 4.54 +/- 0.08 l/min), but endurance
      capacity decreased by 21% from 79 +/- 4 to 62 +/- 4 min (P < 0.001). Endurance
      exercise respiratory exchange ratio was higher in the detrained than in the
      trained state (0.91 +/- 0.01 vs. 0.89 +/- 0.01; P < 0.01). Muscle [K+] values
      were unchanged during exercise and were similar in the trained and detrained
      states. Muscle [Mg2+] values were similar at rest and at minute 40 (30.3 +/- 0.9
      vs. 30.8 +/- 0.6 mmol/kg dry wt) but increased significantly at exhaustion to
      33.8 +/- 1.0 mmol/kg dry wt in the trained state and to 33.9 +/- 0.9 mmol/kg dry
      wt in the detrained state. The elevated muscle [Mg2+] at exhaustion could
      contribute to fatigue in prolonged exercise through an inhibition of Ca2+ release
      from sarcoplasmic reticulum. It is concluded that the endurance capacity can vary
      considerably during detraining without changes in VO2max. Altered substrate
      utilization or changes in electrolyte regulation may account for the reduced
      endurance capacity.

PMID- 8282589
TI  - Effects of posture on abdominal muscle shortening in awake dogs.
AB  - The objective of this study was to examine the effects of posture on tonic and
      phasic expiratory activity of the abdominal muscles in awake dogs. Six
      tracheostomized dogs were chronically instrumented with sonomicrometer
      transducers and bipolar electromyographic electrodes placed in each of the four
      abdominal muscles. To determine the effects of posture on tonic and phasic
      activity of individual abdominal muscles, muscle resting length (Lr) and tidal
      length changes (%Lr), respectively, were measured in awake dogs in the left
      lateral decubitus (LLD), sitting, and standing (STAND) positions. The transversus
      abdominis Lr consistently shortened when the dog was moved from LLD to STAND and
      lengthened when the dog was moved from LLD to the sitting position, and the
      external oblique Lr consistently lengthened when the dog went from LLD to STAND.
      The internal oblique and rectus abdominis had no consistent changes in Lr with a
      change in position. All four abdominal muscles actively shortened (%Lr) more in
      the upright positions. In addition, the internal layer (transversus abdominis and
      internal oblique) actively shortened more than the external layer (rectus
      abdominis and external oblique). In conclusion, both tonic and phasic respiratory
      activity of the abdominal muscles, reflected by changes in Lr and %Lr,
      respectively, were affected by changes in posture.

PMID- 8282590
TI  - Airway and tissue impedances of canine lungs after step volume changes.
AB  - We investigated the changes in pulmonary mechanics in five anesthetized paralyzed
      tracheostomized open-chest dogs after step changes in lung volume. We applied
      small-amplitude (10-ml) volume oscillations at 6 Hz at the tracheal opening for
      50-s periods, during which we applied a step volume change of 250, 500, or 750 ml
      to the lungs. Alveolar capsule measurements of alveolar pressure allowed us to
      calculate cycle-by-cycle values for airway resistance (Raw) and reactance (Xaw)
      and lung tissue resistance (Rti) and reactance (Xti). Before the step changes in
      lung volume, when transpulmonary pressure (Ptp) had a mean value of 0.65 kPa, Raw
      was markedly greater than Rti. The situation was reversed after the step changes,
      however, when Raw decreased and Rti increased. Both Raw and Xaw showed negative
      dependences on Ptp and hence on airway caliber, as expected, and also decreased
      transiently after the step volume changes, almost certainly due to a vagally
      mediated bronchodilation reflex. Both Rti and Xti showed clear linear dependences
      on Ptp and were themselves tightly coupled. Furthermore, our estimate of bulk
      modulus for lung tissue at 6 Hz is comparable to its previously reported values
      at much lower oscillation frequencies.

PMID- 8282591
TI  - Effect of lung volume maintenance during sleep in nocturnal asthma.
AB  - Previous studies have shown that lung volume decreases and airway resistance
      increases during sleep in patients with nocturnal asthma. To determine whether
      the fall in lung volume per se causes the overnight decrement in forced
      expiratory volume in 1 s (FEV1) and/or increase in bronchial responsiveness, we
      investigated the effect of preventing this nocturnal decrease in lung volume. The
      mean volume change on a baseline night was -16.3 +/- 1.6% from presleep values
      and on the volume maintenance night +7.1 +/- 3.0% (P = 0.0001). However, this
      maintenance of lung volume did not alter the overnight decrement in FEV1 (-29.6
      +/- 5.2% baseline vs. -30.2 +/- 5.8% volume maintenance). Similarly, the increase
      in bronchial responsiveness was also unaltered from baseline to volume
      maintenance nights, with presleep provocative concentrations of methacholine
      producing a 20% decrement in FEV1 of 0.28 +/- 0.15 vs. 0.22 +/- 0.7 mg/ml,
      respectively, and postsleep values of 0.07 +/- 0.03 vs. 0.04 +/- 0.02 mg/ml,
      respectively. Thus the fall in lung volume during sleep in the nocturnal
      asthmatic patient is a result, not a cause, of the overnight worsening of lung
      function.

PMID- 8282592
TI  - Interaction of aerobic exercise training and clenbuterol: effects on insulin
      resistant muscle.
AB  - The effects of aerobic exercise training, chronic administration of the selective
      beta 2-adrenergic agonist clenbuterol, and the combination of these two
      treatments on muscle insulin resistance were compared in female obese (fa/fa)
      Zucker rats. Rats were randomly assigned to trained, clenbuterol, clenbuterol
      trained, or control groups. Training consisted of treadmill running for 2 h/day
      at 18 m/min up an 8% grade. Clenbuterol was administered by intubation (0.4-0.8
      mg.kg body wt-1 x day-1) approximately 30 min before the rats ran each day. After
      8 wk of treatment, muscle insulin resistance was assessed via hindlimb perfusion
      in the presence of 8 mM glucose and a submaximal (500 microU/ml) insulin
      concentration. Training increased citrate synthase activity (mumol.g wet wt-1 x
      min-1) by 32-74% and insulin-stimulated glucose uptake by 45%. Clenbuterol
      ingestion induced a 17-29% increase in muscle mass but decreased citrate synthase
      activity by 34-42% and had no effect on muscle glucose uptake. Administration of
      clenbuterol to rats that exercise trained prevented the training-induced
      improvement in insulin-stimulated glucose uptake and attenuated the increases in
      citrate synthase activity. In addition, both clenbuterol-treated groups displayed
      a 42% decrease in beta-adrenergic receptor density. The results indicate that
      clenbuterol administration, possibly through beta-adrenergic receptor
      downregulation, attenuated a cellular reaction essential for the exercise
      training-induced increase in citrate synthase activity and improvement in
      skeletal muscle insulin resistance of the obese Zucker rat.

PMID- 8282593
TI  - Carbohydrate supplementation spares muscle glycogen during variable-intensity
      exercise.
AB  - Effects of carbohydrate (CHO) supplementation on muscle glycogen utilization and
      endurance were evaluated in seven well-trained male cyclists during continuous
      cycling exercise that varied between low [45% maximal O2 uptake (VO2 max)] and
      moderate intensity (75% VO2 max). During each exercise bout the subjects received
      either artificially flavored placebo (P), 10% liquid CHO supplement (L; 3 x 18 g
      CHO/h), or solid CHO supplement (S; 2 x 25 g CHO/h). Muscle biopsies were taken
      from vastus lateralis during P and L trials immediately before exercise and after
      first (124 min) and second set (190 min) of intervals. Subjects then rode to
      fatigue at 80% VO2 max. Plasma glucose and insulin responses during L treatment
      reached levels of 6.7 +/- 0.7 mM and 70.6 +/- 17.2 microU/ml, respectively, and
      were significantly greater than those of P treatment (4.4 +/- 0.1 mM and 17.7 +/-
      1.6 microU/ml) throughout the exercise bout. Plasma glucose and insulin responses
      of S treatment were intermediate to those of L and P treatments. Times to fatigue
      for S (223.9 +/- 3.5 min) and L (233.4 +/- 7.5 min) treatments did not differ but
      were significantly greater than that of P treatment (202.4 +/- 9.8 min). After
      the first 190 min of exercise, muscle glycogen was significantly greater during L
      (79 +/- 3.5 mumol/g wet wt) than during P treatment (58.5 +/- 7.2 mumol/g wet
      wt). Furthermore, differences in muscle glycogen concentrations between L and P
      treatments after 190 min of exercise and in time to fatigue for these treatments
      were positively related (r = 0.76, P < 0.05). These results suggest that CHO
      supplementation can enhance prolonged continuous variable-intensity exercise by
      reducing dependency on muscle glycogen as a fuel source.

PMID- 8282594
TI  - Effect of isoproterenol on peripheral airway pressure-diameter behavior.
AB  - I radiographically evaluated the pressure-diameter relationships of peripheral
      airways (average diameter approximately 2 mm at total lung capacity) in a
      collaterally ventilating lung segment in 22 caudal dog lung lobes. Eleven lobes
      were studied when freshly excised, and 11 lobes were studied after being rinsed
      with 0.5% isoproterenol. Airways within the segment (intrasegmental) and a
      control region of similarly sized airways external to the segment were studied.
      Radiographs were taken when airway opening pressure (Pao) equaled pressure in the
      segment (Ps) (homogeneous case) and when Pao was 5, 10, or 15 cmH2O greater than
      Ps (nonhomogeneous case). Airway diameter was calculated as a fraction of the
      diameter at Pao = Ps = 25 cmH2O. The response of intrasegmental airways to
      increases in pressure in the homogeneous case (Ps = Pao) and nonhomogeneous case
      (Ps > Pao) differed between freshly excised and isoproterenol-rinsed lobes. I
      conclude that dilating peripheral airways by decreasing bronchomotor tone limits
      the extent to which they can respond to a regional increase in alveolar pressure.

PMID- 8282595
TI  - Effect of estradiol on the temporal pattern of exercise-induced tissue glycogen
      depletion in male rats.
AB  - The effect of 17 beta-estradiol 3-benzoate (10 micrograms.01 ml of sunflower oil
      1 x 100 g body wt-1) on the temporal pattern of exercise-induced tissue glycogen
      depletion and tissue lipid availability during submaximal treadmill running was
      determined in male rats. Animal were administered estradiol or oil for 5 days and
      were then time matched for motorized treadmill running for 30, 60, 90, or 120
      min. Significant depletion of liver, soleus muscle, and red and white vastus
      lateralis muscle tissue glycogen occurred in oil-administered animals run between
      30 and 120 min. The greatest extent of tissue glycogen depletion occurred during
      the first 30 min of exercise with the rate of glycogen depletion slowing between
      30 and 120 min of exercise. Administration of estradiol attenuated the temporal
      pattern of glycogen depletion in both liver and muscle tissues. Significant
      depletion of red and white vastus glycogen of estradiol-administered animals did
      not occur until 90 and 120 min of exercise, respectively. Administration of
      estradiol significantly increased resting plasma free fatty acids and red and
      white vastus triacylglycerol content. These data indicate that estradiol
      administration for 5 days resulted in significant glycogen sparing of liver and
      muscle tissues during submaximal treadmill running for up to 120 min by altering
      the temporal pattern of glycogen depletion of male rats secondary to an estradiol
      mediated increase in availability of lipid substrate during exercise.

PMID- 8282596
TI  - Measuring intrasubject variability: use of the jacknife in doubly labeled water
      experiments.
AB  - The doubly labeled water technique measures energy expenditure; however, very
      little has appeared in the literature regarding estimation of the intrasubject
      variation. By use of a statistical resampling procedure called the jackknife, the
      standard deviation of the determination of energy expenditure in each subject is
      evaluated. Jackknife methods exploit the regression techniques that are already
      used with the doubly labeled water technique and are very easy to implement.
      Estimates of sample sizes for future experiments can easily be done with the
      jackknife. These formulas give the number of determinations of isotopic
      enrichment of hydrogen and oxygen over time that are needed to achieve a given
      degree of accuracy in estimating energy expenditure. An example with two human
      subjects illustrates the methodology of the jackknife.

PMID- 8282597
TI  - Effect of fat emulsion infusion and fat feeding on muscle glycogen utilization
      during cycle exercise.
AB  - Elevated plasma fatty acids have been shown to spare muscle glycogen during
      exercise. However, on the basis of recent findings, the saturation of fatty acids
      may influence this response. The purpose of this study was to determine whether
      saturated or unsaturated fatty acids affected muscle glycogenolysis to varying
      degrees during cycle exercise. Five healthy men completed three 60-min cycle
      ergometer trials (EX) at approximately 70% maximal O2 uptake (VO2max).
      Triglyceride levels were elevated by a fat feeding (FF) composed of 90% saturated
      fatty acids (heavy whipping cream, 90 g) or by the infusion of Intralipid (IL;
      Clintec Nutrition; 45 ml/h of 20% IL, 9.0 g), which was 85% unsaturated. A
      control trial (CON) consisted of a light breakfast (43 g carbohydrate and 1 g
      fat). Heparin (2,000 U) was administered 15 min before EX in FF and IL trials,
      resulting in one- and threefold increases in free fatty acid (FFA) levels in IL
      and FF, respectively. Pre-EX muscle glycogen did not differ. The utilization of
      muscle glycogen during 60 min of EX was less (P < 0.05) during the FF (60.0 +/-
      5.2 mmol/kg wet wt) and IL (58.6 +/- 6.2 mmol/kg wet wt) compared with CON (81.8
      +/- 7.5 mmol/kg wet wt). There was no difference between FF and IL in the amount
      of glycogen utilized. Serum triglyceride levels were greater (P < 0.05) at
      preheparin in FF (1.58 +/- 0.37 mmol/l) and IL (0.98 +/- 0.13 mmol/l) compared
      with CON (0.47 +/- 0.14 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282598
TI  - Angiotensin-converting enzyme preferentially hydrolyzes trans isomer of proline
      containing substrate.
AB  - An analysis of the hydrolysis kinetics of the synthetic angiotensin-converting
      enzyme (ACE) substrate benzoyl-phenylalanyl-alanyl-proline (BPAP) in the intact
      lung suggested that 12-15% of the BPAP was in a form that could not be hydrolyzed
      by ACE in the time course of a single pass through the lungs [C. A. Dawson et al.
      Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H853-H865, 1989]. BPAP has been
      found to exist as a mixture of cis and trans isomers in a ratio of approximately
      14:86 in aqueous solution at equilibrium. Thus, one possible explanation for the
      incomplete hydrolysis of BPAP on passage through the intact lung is that the
      trans form is the preferred substrate for ACE. To examine this hypothesis, we
      measured BPAP hydrolysis by ACE in vitro over a range of ACE concentrations and
      in the presence and absence of the peptidyl-prolyl cis-trans isomerase
      cyclophilin. In the presence of a sufficient concentration of ACE and in the
      absence of cyclophilin, hydrolysis of [3H]BPAP by ACE followed biexponential
      progress curves, consistent with the hypothesis that the rate of hydrolysis of
      the majority (approximately 87%) of the substrate is proportional to ACE
      concentration, whereas the hydrolysis rate of the remaining substrate fraction is
      independent of enzyme concentration. The addition of cyclophilin resulted in an
      increase in the ACE-independent rate constant, an effect that was reversed by the
      cyclophilin inhibitor cyclosporin A. These results suggest that the enzyme
      independent rate constant represents the rate of cis-trans isomerization and that
      the enzyme-dependent rate constant represents the hydrolysis of the trans
      isomer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282599
TI  - Alveolar liquid pressure measured in the intact rabbit chest by micropuncture.
AB  - Previous measurements in isolated lung showed that alveolar liquid pressure was
      near the pleural pressure at a lung volume near functional residual capacity
      (FRC). In this study we verified that alveolar liquid pressure in vivo was
      similar to that of the isolated lung. In anesthetized paralyzed rabbits (3-4 kg,
      n = 9) ventilated with 100% O2 in the left lateral position, we made a pleural
      window between the fifth and sixth ribs near midchest by removing tissue down to
      the parietal pleura. Window height was 6 cm above the base of the lung. During
      apnea, alveolar liquid and pleural pressures were measured by puncturing through
      the pleural window with micropipettes connected to a servo-nulling pressure
      measuring system. Pressures were measured at airway pressures of 0 (FRC) and 10
      cmH2O both in vivo and postmortem. In vivo, alveolar liquid and pleural pressures
      relative to ambient pressure averaged -2.3 +/- 1.4 (SD) and -1.8 +/- 0.9 cmH2O at
      FRC and increased to 3.3 +/- 1.8 and 1.8 +/- 1.6 cmH2O after inflation to an
      airway pressure of 10 cmH2O, respectively. Similar values were obtained
      postmortem. These results were similar to previous measurements in the isolated
      lung.

PMID- 8282600
TI  - Effect of growth hormone on gastrocnemius muscle of aged rats after
      immobilization: biochemistry and morphology.
AB  - Immobilization of limbs of aged animals is associated with swift muscular damage
      and atrophy. We investigated the effect of rat growth hormone (rGH) on
      immobilized hindlimb muscles of 26-mo-old rats. Administration of rGH
      significantly reduced muscle weight loss and muscle protein oxidation caused by
      immobilization. Capillary blood volume, measured by photoplethysmography of the
      hindlimb, showed a 34% reduction in immobilized animals, which was eliminated by
      rGH. The activity of creatine phosphokinase in immobilized gastrocnemius muscle
      was significantly reduced by immobilization. This damage was diminished by rGH
      administration. Similarly, the increase in acid phosphatase activity in
      immobilized muscle was reduced after rGH treatment. Morphologically, marked
      muscle atrophy and fiber disorientation were observed in immobilized limbs.
      Therapy with rGH prevented some of these changes. These results indicate that
      administration of rGH may provide a useful means to attenuate the degenerative
      effects of limb immobilization of aged rats, as evident from physiological,
      biochemical, and morphological parameters.

PMID- 8282601
TI  - Effect of lung lavage on the stress relaxation of the respiratory system.
AB  - To test the hypothesis that lowering the concentrations of surfactant molecules
      at the gas-liquid interface increases viscoelastic dissipation in the lungs, the
      amplitude and time course of stress relaxation were quantified before and after
      lavage of the lungs with warm saline in five newborn and five 8-wk-old
      anesthetized piglets. Stress relaxation was separated from other dissipative
      pressure losses by fitting the pressure decays that follow airway occlusions
      performed during a period of constant inspiratory flow to a double-exponential
      regression. The amplitude of stress relaxation (defined by the term of the
      regression with the longest time constant) related linearly to the changes in
      respiratory system volume and elastic recoil preceding the occlusions both before
      and after the lavage. Lung lavage increased the slope of both relationships
      without altering the time course of the relaxations. In addition to being
      consistent with the proposed hypothesis, these results suggest that viscoelastic
      pressure losses remain linked to the elastic stresses generated during lung
      inflation, as proposed by Fredberg and Stamenovic's structural dumping theory (J.
      Appl. Physiol. 67: 2408-2419, 1989).

PMID- 8282602
TI  - Effect of training on eccentric exercise-induced muscle damage.
AB  - Eccentric muscle contractions generate delayed onset muscle soreness (DOMS),
      possibly as a result of the high tensions involved causing muscle damage. Muscle
      function, serum indicators of muscle damage, and DOMS were investigated
      throughout a training regimen that involved a 40-min eccentric walk down a 25%
      gradient on a treadmill at 6.4 km/h once a week for 8 wk. Serum creatine kinase
      and myoglobin concentrations were used as indicators of muscle damage, and both
      demonstrated a delayed increase after the exercise protocol. The muscles that
      contracted eccentrically exhibited low-frequency fatigue, as well as decreases in
      muscle fatigability and maximal voluntary contraction force, which were greatest
      immediately postexercise. Although the results show that training reduces DOMS,
      the serum muscle protein response, and muscle function impairment, the time
      courses of these adaptations are different. It is suggested that the function of
      the muscle can be impaired without apparent muscle damage.

PMID- 8282603
TI  - Upper airway muscle activity during sustained hypoxia in awake humans.
AB  - To examine the effects of sustained hypoxia on upper airway and chest wall muscle
      activity in humans, we measured genioglossus muscle (GG) activity, inspiratory
      intercostal muscle (IIM) activity, and ventilation during sustained hypoxia in 17
      normal subjects and 17 patients with obstructive sleep apnea (OSA). The trial of
      sustained hypoxia was performed as follows: after an equilibration period of 3
      min, isocapnic hypoxia (arterial O2 saturation = 80 +/- 2%) was maintained for 20
      min. GG EMG was measured with a fine-wire electrode inserted percutaneously, and
      IIM EMG was measured with surface electrodes. Ventilatory response to sustained
      hypoxia was initially increased and subsequently decreased. Stable phasic GG
      activity during spontaneous tidal breathing was observed in 6 normal subjects and
      10 patients with OSA. Responses of GG and IIM activities to sustained hypoxia
      showed a biphasic response qualitatively similar to the ventilatory response in
      these 16 subjects. The absolute value of the subsequent decline in GG activity
      was similar to that of the initial increase, whereas the subsequent decline in
      IIM activity was smaller than that of the initial increase. Percent GG activity
      was significantly lower than both percent IIM activity and percent minute
      ventilation during the decline and plateau phases. There were no significant
      differences in ventilatory and EMG responses between the normal subjects and the
      patients with OSA. We conclude that, during wakefulness, upper airway muscle
      activity declined to a greater extent than inspiratory pump muscle activity
      during sustained hypoxia.

PMID- 8282604
TI  - Training does not affect zero-trans lactate transport across mixed rat skeletal
      muscle sarcolemmal vesicles.
AB  - Hindlimb muscle sarcolemmal vesicles were purified from three age-matched groups
      of female Sprague-Dawley rats: sedentary control (CON; n = 10), sprint trained
      (ST; n = 8), and endurance trained (ET; n = 9). Membrane isolations from the
      three groups were not significantly different in protein yield or purification
      index. Blood lactate concentration was determined in resting CON rats and running
      ET and ST rats during the final week. Both the ST and ET groups were
      significantly higher in citrate synthase (vs. CON) in the soleus and mid-vastus
      lateralis. The time course of 1 mM L-(+)-lactate uptake in vesicles from the
      three groups showed no significant difference at any of the five time points
      tested under zero-trans conditions. Saturation kinetics were examined at nine
      lactate concentrations, and Lineweaver-Burk plots revealed no difference between
      groups in apparent Michaelis-Menten constant or maximal transport velocity.
      Vesicles from CON and ET rats were used to investigate cis inhibition of 0.1 mM L
      (+)-lactate transport by four unlabeled monocarboxylates: L-(+)-lactate, D-(-)
      lactate, pyruvate, and alpha-cyanohydroxycinnamate at 0.1, 1.0, and 10 mM. Under
      pH gradient-stimulated L-(+)-lactate transport conditions, cis inhibition was
      affected by neither D-(-)-lactate nor endurance training. We conclude that the
      lactate transporter has distinct cis-inhibitory specificity, is stereospecific,
      and is stimulated when confronted with parallel lactate and proton gradients but
      that spring and endurance training do not alter lactate transport rate or
      capacity under these conditions.

PMID- 8282605
TI  - Blood volume expansion, preeclampsia, and infant birth weight at high altitude.
AB  - Low blood volume (BV) during pregnancy is associated with intrauterine growth
      retardation and preeclampsia, which are more common at high altitude (HA) than at
      low altitude. We hypothesized that reduced BV expansion during pregnancy
      predisposed some women to develop preeclampsia and/or have lower-birth-weight
      infants at HA. BV was lower in 34 HA residents (3,100 m) than in 22 moderate
      altitude residents (1,600 m) while nonpregnant (58.3 +/- 1.2 vs. 72.3 +/- 1.3
      ml/kg; P < 0.001) and 36 wk pregnant (69.9 +/- 1.9 vs. 83.3 +/- 3.6 ml/kg; P <
      0.01). BV fell between weeks 24 and 36 of pregnancy, and total BV increment with
      pregnancy was less in women who developed preeclampsia or transient hypertension
      at HA (n = 12). At HA, total blood and plasma volume expansion and arterial O2
      saturation correlated negatively with the highest mean arterial pressure recorded
      during pregnancy (r = -0.73, P < 0.01 and r = -0.58, P < 0.01, respectively).
      Total BV and late pregnancy change in BV correlated positively with infant birth
      weight. We concluded that BV expansion in normotensive pregnancy at HA vs.
      moderate altitude was similar but that nonpregnant BV was less among HA women,
      accounting for the low BV in pregnancy. HA women who developed preeclampsia or
      transient hypertension had less BV expansion, particularly during the third
      trimester, which was associated with smaller infants.

PMID- 8282606
TI  - Active transport and passive liquid movement in isolated perfused rat lungs.
AB  - The isolated perfused liquid-filled rat lung in a "pleural bath" was the model
      used to study liquid exchange across the lung epithelium. Active transport and
      passive solute movement between the air space, the vascular perfusate, and the
      bath result in concentration changes of the three markers (Evans blue-tagged
      albumin, 22Na+, and [3H]mannitol) instilled in the air space. A mathematical
      model was developed to estimate the active and passive solute transports and to
      interpret the results. Rat lungs were perfused at left atrial and pulmonary
      arterial pressures of 0 and 8 mmHg, respectively. Six rat lung experiments were
      conducted at 37 degrees C and six at 4 degrees C. The normothermic experiments
      demonstrate that active transport accounts for 26% of the Na+ movement out of the
      air space (17.3 +/- 0.7 nm/s) and that passive mechanisms account for the
      remaining 74% (48.0 +/- 5.7 nm/s). Hypothermia inhibits lung liquid clearance but
      does not affect passive solute movement, suggesting that lung liquid clearance is
      effected by active Na+ transport mechanisms.

PMID- 8282607
TI  - Dynamics of carotid body responses in vitro in the presence of CO2-HCO3-: role of
      carbonic anhydrase.
AB  - The role of carbonic anhydrase (CNA) in the dynamics of carotid body (CB)
      function was tested by studying the effects of the membrane-permeable CNA
      inhibitor methazolamide on the chemosensory responses of the cat CB, perfused and
      superfused in vitro with cell-free and modified Tyrode solution at 36.5 +/- 0.5
      degrees C in the presence of CO2-HCO3- (PO2 = 120 Torr, PCO2 = 32 Torr, pH =
      7.40). The bulk of CO2 flow to the CB from the external milieu was overwhelmingly
      large relative to the metabolic production of CO2 in the CB. Accordingly, the
      relative contribution of the endogenous CO2 to the CB responses was small. The
      chemosensory nerve discharges were recorded from the whole desheathed carotid
      sinus nerve. The responses to acidic hypercapnia (PCO2 = 50-60 Torr, pH = 7.20
      7.10), hypoxia (PO2 = 25 and 50 Torr), perfusate flow interruption, and bolus
      injections of sodium cyanide (20-40 nmol) were tested. To contrast, we also
      measured the effects of nicotine (2-4 nmol), which may act at sites other than
      those for O2 and CO2. Methazolamide (30 mg/l) in the perfusate at constant PCO2
      and pH reduced the baseline activity and delayed the responses to step changes in
      PCO2 (and concomitantly pH) and PO2 and to cyanide but not to nicotine. The
      steady-state responses to these stimuli, measured as differences from control,
      were reduced, but not significantly. The initial overshoots seen with step
      changes in both high PCO2 and low PO2 were eliminated.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8282608
TI  - Carnitine delays rat skeletal muscle fatigue in vitro.
AB  - Carnitine has been used to enhance human exercise performance. To test the
      hypothesis that carnitine can directly modify skeletal muscle function, fatigue
      of isolated rat skeletal muscle strips was studied in vitro. Carnitine (10 mM)
      did not modify the initial force of soleus contraction. The time over which force
      declined by 50% during repetitive electrical stimulation of the soleus muscle
      (fiber type I) was prolonged 25% in the presence of 10 mM carnitine. In contrast,
      carnitine had no effect on the fatigue of extensor digitorum longus muscle strips
      (fiber type II). The beneficial effect of carnitine on soleus muscle strips was
      not observed if the routine 30-min preincubation in the presence of carnitine was
      decreased to 5 min; it was associated with a five- to sixfold increase in muscle
      total carnitine content and a 50-150% increase in muscle long-chain acylcarnitine
      content. Carnitine did not consistently modify lactate accumulation or glycogen
      depletion during the fatigue protocol. Incubation with propionyl-L-carnitine
      resulted in a decreased initial force of contraction and a delay in reaching
      maximal contractile force. Thus, carnitine can directly improve the fatigue
      characteristics of muscles enriched in type I fibers.

PMID- 8282609
TI  - Capillary oxygen transport during severe hypoxia: role of hemoglobin oxygen
      affinity.
AB  - The efficacy of an increased hemoglobin oxygen affinity [decreased oxygen half
      saturation pressure of hemoglobin (P50)] on capillary oxygen transport was
      evaluated in the hamster retractor muscle under conditions of a severely limited
      oxygen supply resulting from the combined effects of a 40% reduction in systemic
      hematocrit and hypoxic ventilation (inspired oxygen fraction 0.1). Two groups of
      hamsters were utilized: one with a normal oxygen affinity (untreated; P50 = 26.1
      +/- 2.4 Torr) and one with an increased oxygen affinity (treated; P50 = 15.7 +/-
      1.4 Torr) induced by the chronic short-term administration of sodium cyanate.
      Using in vivo video microscopy and image analysis techniques, we determined
      oxygen saturation and associated hemodynamics at both ends of the capillary
      network. During hypoxic ventilation, the decrease in oxygen saturation across the
      network was 3.6% for untreated animals compared with 9.9% for treated animals.
      During hypoxia, estimated end-capillary PO2 was significantly higher in the
      untreated animals. These data indicate that, at the capillary level, a decreased
      P50 is advantageous for tissue oxygenation when oxygen supply is severely
      compromised, because normal oxygen losses in capillaries are maintained in
      treated but not in untreated animals. The data are consistent with the presence
      of a diffusion limitation for oxygen during severe hypoxia in animals with a
      normal hemoglobin oxygen affinity.

PMID- 8282610
TI  - Determinants of maximal oxygen uptake in rats acclimated to simulated altitude.
AB  - The effect of acclimation to hypoxia on maximal O2 uptake (VO2max), maximal
      cardiac output (Qmax), and arteriovenous O2 concentration difference (a-vCO2) was
      studied in male Sprague-Dawley rats acclimated for 3 wk to a barometric pressure
      of approximately 380 Torr (A rats). Nonacclimated control animals were pair-fed
      littermates maintained at an ambient barometric pressure of approximately 740
      Torr (NA rats). Both A and NA rats exercised maximally on a treadmill with
      inspired PO2 maintained at either approximately 72 or 145 Torr. Arterial blood O2
      concentration was significantly higher in A than in NA rats (16.0 +/- 0.6 vs.
      12.4 +/- 0.3 ml/dl in hypoxia and 28.4 +/- 1.5 vs. 20.1 +/- 0.9 ml/dl in
      normoxia, respectively; both P < 0.05). During hypoxic exercise VO2max was
      slightly but significantly higher in A than in NA subjects (55.3 +/- 1.3 vs. 48.8
      +/- 1.1 ml STPD.min-1 x kg-1; P < 0.05). In hypoxia a-vCO2 was 16.6 +/- 0.6 and
      12.4 +/- 0.4 ml/dl and Qmax was 401 +/- 17 and 489 +/- 9 ml.min-1 x kg-1 in A and
      NA subjects, respectively (both P < 0.05). A rats showed both lower maximal heart
      rate and lower maximal stroke volume during hypoxic exercise. In normoxia there
      was no significant difference in VO2max between A and NA rats (71.8 +/- 2.7 vs.
      73.9 +/- 3.1 ml.min-1 x kg-1). As with hypoxia, in normoxia a-vCO2 was
      significantly higher and Qmax was significantly lower in A than in NA
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282611
TI  - Neutral endopeptidase inhibition attenuates development of hypoxic pulmonary
      hypertension in rats.
AB  - Neutral endopeptidase (NEP) inhibition is thought to blunt hypoxic pulmonary
      hypertension by reducing atrial natriuretic peptide (ANP) metabolism, but this
      hypothesis has not been confirmed. We measured NEP activity, guanosine 3',5'
      cyclic monophosphate (cGMP) production, plasma ANP levels, and cardiac ANP
      synthesis in rats given an orally active NEP inhibitor (SCH-34826) during 3 wk of
      hypoxia. Under normoxic conditions, SCH-34826 had no effect on plasma ANP levels
      but reduced pulmonary and renal NEP activity by 50% and increased urinary cGMP
      levels (60 +/- 6 vs. 22 +/- 4 pg/mg creatinine; P < 0.05). Under hypoxic
      conditions, SCH-34826-treated rats had lower plasma ANP levels (1,259 +/- 361 vs.
      2,101 +/- 278 pg/ml; P < 0.05), lower right ventricular systolic pressure (53 +/-
      5 vs. 73 +/- 2 mmHg; P < 0.05), lower right ventricle weight-to-left
      ventricle+septum weight ratio (0.47 +/- 0.04 vs. 0.53 +/- 0.03; P < 0.05), and
      less muscularization and percent medial wall thickness of peripheral pulmonary
      arteries (22 +/- 5 vs. 45 +/- 8% and 17 +/- 1 vs. 25 +/- 1%, respectively; P <
      0.05 for all values) than did rats treated with vehicle alone. These values were
      not affected by SCH-34826 under normoxic conditions. SCH-34826 decreased right
      ventricular ANP tissue levels in hypoxic rats (27 +/- 10 vs. 8 +/- 1 ng/mg
      protein; P < 0.05) but did not affect steady-state ANP mRNA levels. We conclude
      that NEP inhibition blunts pulmonary hypertension without increasing plasma ANP
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282612
TI  - Dynamic behavior of alveolar surface-to-volume ratio in live dogs by light
      scattering stereology.
AB  - To investigate the behavior of the surface-to-volume ratio (S/V) in lung lobes of
      live dogs, we measured the backscattered light pattern produced by applying a
      laser beam to the pleural surface. This pattern was used to estimate the optical
      mean free path, which is approximately proportional to the inverse square of the
      geometric S/V. Measurements were performed in mechanically ventilated animals
      with the chest widely opened. We found that during quasi-static large volume
      excursion, S/V changed approximately as the one-third power of lung volume but
      with hysteresis such that S/V during deflation was higher than during inflation.
      This finding is consistent with a relatively large stress hysteresis of surface
      tension compared with that of the tissue. During tidal breathing, however, the
      geometric hysteresis was inconsistent among animals at low frequency but was
      consistently changed at higher frequencies in a direction suggesting a lesser
      role of surface tension relative to tissue stress hysteresis.

PMID- 8282613
TI  - Geometric hysteresis in pulmonary surface-to-volume ratio during tidal breathing.
AB  - We investigated the dynamic history dependence of lung surface area-to-volume
      ratio (S/V) during tidal breathing in live rabbits with use of our recently
      developed technique of diffuse optical scattering. We also examined the effect of
      methacholine (continuous intravenous infusion, 1-10 micrograms.kg-1.min-1) on
      lung micromechanics with the same technique. Animals were anesthetized,
      tracheostomized, and mechanically ventilated, and the left lung was exposed
      through a thoracotomy. An optical fiber delivering light from a He-Ne laser was
      attached normal to the pleural surface, producing a circular light pattern on the
      pleural surface from diffusively scattered light within the parenchyma. The
      pattern of light intensities was measured using a CCD video camera connected to a
      computer. S/V during tidal breathing changed in a manner qualitatively consistent
      with geometric similarity. There was a small but significant hysteresis in S/V
      vs. volume, with S/V inspiration greater than S/V expiration at the same volume.
      However, during methacholine challenge, the sense of hysteresis reversed; S/V
      inspiration was less than S/V expiration at isovolume points. Moreover, S/V
      during methacholine challenge systematically decreased at all lung volumes
      compared with control. These findings suggest that 1) during normal tidal
      breathing, stress hysteresis in ductal tissue is larger than septal stress
      hysteresis (septal tissue plus surface tension) and 2) the effect of methacholine
      on tissue in the septa is greater than the corresponding effect in ductal tissue.

PMID- 8282614
TI  - Prediction of body composition in premenopausal females from dual-energy X-ray
      absorptiometry.
AB  - Four methods for predicting body composition were compared in premenopausal
      females (n = 100), 28-39 yr old, by using underwater weighing (UWW) as the
      criterion method. The four methods were dual energy X-ray absorptiometry (DEXA),
      skinfolds, bioelectrical impedance, and body mass index. The sample had a mean
      percent fat (%fat) of 29.7 +/- 6.8% (SD) by DEXA and 29.9 +/- 5.8% measured by
      UWW. DEXA yielded a standard error of estimate (SE) of 2.4% (r = 0.91) for the
      prediction of %fat from UWW. When %fat was estimated from other methods, larger
      SEs were obtained: 3.0% for skin-folds, 3.3% for body mass index, and 2.9% for
      bioelectrical impedance (height2/resistance) plus weight. Individual body density
      values derived from UWW were corrected for bone mineral variation. DEXA predicted
      the corrected body density with a lower SE (0.0040 vs. 0.0053 g/ml) than the
      original density values. We conclude that DEXA was a precise method and
      correlated highly with fat-free body weight and %fat from UWW in this homogeneous
      female sample.

PMID- 8282615
TI  - Inhibitor sensitivity of pulmonary vascular carbonic anhydrase.
AB  - The inhibitor sensitivity of pulmonary vascular carbonic anhydrase (CA) was
      examined in situ to identify the specific isozyme responsible for vascular
      activity and to study its distribution in the lung. Vascular CA activity was
      monitored in isolated rat lungs by measuring the rate of CO2 excretion and the
      magnitude of postcapillary CO2-HCO(3-)-H+ disequilibria. Lungs were perfused with
      isotonic salines containing gluconate, sulfate, Cl-, or I-, with or without
      sulfonamide derivatives. Effects of a CA inhibitor purified from porcine blood
      plasma were also determined. Vascular CA activity was unaffected by gluconate,
      sulfate, Cl-, and I- (< or = 100 mM). Sulfonamides with vastly different rates of
      membrane permeation (i.e., readily permeating ethoxzolamide, slowly permeating
      acetazolamide, and membrane-impermeant quaternary ammonium sulfanilamide) were
      capable of accessing all vascular CA with similar rates of access. The porcine
      inhibitor of CA (340 nM) produced a significant, but submaximal, inhibition of
      vascular CA activity. The data suggest that pulmonary vascular activity reflects
      a high-activity membrane-bound isozyme, CA IV, which is located on the
      extracellular luminal surface of capillary endothelial cells.

PMID- 8282616
TI  - Elevated interstitial fluid volume in soleus muscles unweighted by spaceflight or
      suspension.
AB  - Recent evidence by Kandarian et al. (J. Appl. Physiol. 71: 910-914, 1991)
      indicates that prolonged (28 days) unweighting of the rat soleus by hindlimb
      suspension results in a substantial increase in interstitial fluid volume (IFV),
      as defined by the inulin space. The lack of any significant difference in
      absolute IFV values between unweighted and control groups suggested that this
      elevated IFV was a consequence of muscle atrophy. Using young female rats, we
      directly tested this hypothesis by comparing the early responses of soleus muscle
      weight and IFV with unweighting by tail-cast suspension or actual exposure to
      microgravity during spaceflight. Significant differences from control were first
      observed after 3 days of suspension unweighting for soleus wet weight (-14%; P <
      0.01) and IFV (+35%; P < 0.01) and increased further after 6 days (-32% and +53%,
      respectively; both P < 0.001). After 5.4 days of spaceflight, soleus wet weight
      was 38% less and IFV was 52% greater than control (both P < 0.001). A highly
      significant negative correlation between soleus wet weight and IFV for all groups
      was observed (r = -0.70, P < 0.001). These data indicate that elevated soleus IFV
      develops at an early time point during unweighting and that there is a direct
      relationship between the magnitude of this increase in IFV and the extent of
      muscle atrophy. This relationship also exists in soleus muscles unweighted by
      exposure to a microgravity environment.

PMID- 8282617
TI  - Anaerobic energy release in working muscle during 30 s to 3 min of exhausting
      bicycling.
AB  - To examine the anaerobic energy release during intense exercise, 16 healthy young
      men cycled as long as possible at constant powers chosen to exhaust the subjects
      in approximately 30 s, 1 min, or 2-3 min. Muscle biopsies were taken before and
      approximately 10 s after exercise and analyzed for lactate, phosphocreatine
      (PCr), and other metabolites. O2 uptake was measured for determination of the
      accumulated O2 deficit (a whole body measure of the anaerobic energy release),
      and this indirect measure of the anaerobic energy release was compared with a
      direct value obtained from measured muscle metabolites. Muscle lactate
      concentration rose by 30.0 +/- 1.2 mmol/kg and muscle PCr concentration fell by
      12.4 +/- 0.9 mmol/kg during the 2-3 min of exhausting exercise. The anaerobic ATP
      production was consequently 58 +/- 2 mmol/kg wet muscle mass, which may be the
      maximum anaerobic energy release for human muscle during bicycling. Because the
      anaerobic ATP production was 6 and 32% less for 1 min and 30 s of exercise,
      respectively, than for 2 min of exercise (P < 0.03), 2 min of exhausting exercise
      may be required for maximal use of anaerobic sources. Lactate production provided
      three times more ATP than PCr breakdown for all three exercise durations. There
      was a close linear relationship between the rates of anaerobic ATP production in
      muscle and the value estimated for the whole body by the O2 deficit (r = 0.94).
      This suggests that the accumulated O2 deficit is a valid measure of the anaerobic
      energy release during bicycling.

PMID- 8282618
TI  - Alveolar epithelial injury and pleural empyema in acute P. aeruginosa pneumonia
      in anesthetized rabbits.
AB  - We developed an experimental model of acute Pseudomonas aeruginosa pneumonia in
      anesthetized ventilated rabbits to determine whether bacterial-induced injury to
      the alveolar epithelium would occur and the effect of the injury on the pleural
      space. Dose-response studies established that 10(9) colony-forming units of P.
      aeruginosa (wild-type strain, PAO-1) were required to injure the epithelial
      barrier and to cause pleural empyema with exudative pleural effusions that
      contained both the instilled alveolar protein tracer and P. aeruginosa. We
      explored the mechanisms of P. aeruginosa-induced lung and pleural injury by using
      three isogenic bacterial strains to compare several extracellular virulence
      products. PAO-S21, which carries an insertion mutation in a regulatory gene that
      prevents the production of exoenzyme S, resulted in no lung or pleural injury.
      PAO-R1, which carries a deletion in a regulatory gene that controls the
      production of elastase and alkaline protease, caused the same degree of lung and
      pleural injury as PAO-1 did. Instillation of PLC-SRN, which has both structural
      genes encoding phospholipase C activity deleted, resulted in a moderate reduction
      in alveolar epithelial injury. Although other products may be involved, exoenzyme
      S and phospholipase C are important in mediating injury to the alveolar
      epithelial barrier in acute P. aeruginosa pneumonia in rabbits.

PMID- 8282619
TI  - Age and training alter collagen characteristics in fast- and slow-twitch rat limb
      muscle.
AB  - This study evaluated the single and interactive effects of age and training
      status on selected collagen parameters in two rodent locomotor skeletal muscles
      contrasting in fiber type composition. Gastrocnemius (GAST) and soleus (SOL)
      muscles from both trained (10 wk of daily treadmill running) and sedentary young
      adult (5-mo-old), middle-aged (15-mo-old), and old (23-mo-old) female Fischer 344
      rats were evaluated for concentrations of collagen (measured by hydroxyproline
      concentration ([OH-Pro])) and of the predominant nonreducible lysine aldehyde
      derived collagen cross-link hydroxylysylpyridinoline ([HP]). Maximal aerobic
      capacity was significantly elevated in all three trained groups compared with
      sedentary age-matched control groups. Slow-twitch SOL had a significantly higher
      [OH-Pro] than fast-twitch GAST (P < 0.05). Although aging had no effect on [OH
      Pro] in GAST, in SOL a significant increase with age was seen (P < 0.02). In
      sedentary rats both GAST and SOL [HP] increased with age, with this increase
      being more pronounced for SOL. Additionally, although training had no effect on
      the aging-associated increase in GAST [HP], it prevented the rise seen in SOL.
      The observed training-induced reduction in SOL [HP] presumably reflects exercise
      recruitment and subsequent stimulation of collagen synthesis and degradation
      rates in this muscle. We conclude that both aging and training affect the
      extracellular matrix in rodent limb skeletal muscle.

PMID- 8282620
TI  - O2 uptake kinetics above and below the lactic acidosis threshold during
      sinusoidal exercise.
AB  - O2 uptake (VO2) kinetics at the onset of a constant work rate exercise are
      difficult to describe for work rates above the lactic acidosis threshold (LAT),
      because the steady-state level of VO2 response can usually not be identified. To
      describe the ability of the O2 transport system to deliver and the cells to
      utilize O2 above the LAT relative to that below the LAT, we applied a fluctuating
      (sinusoidal) variation of work rate. After 4 min of constant work at the midpoint
      of the sinusoidal work rate, a fluctuating work rate, at a period of 4 min, was
      applied below the LAT for the next 16 min. This was repeated in a range of work
      rates above the LAT with the same sine-wave amplitude. VO2 response appeared to
      follow a sinusoidal pattern similar to that of work rate for below- and above-LAT
      exercise. However, the amplitude of the VO2 response was significantly reduced
      (5.4 +/- 2.6 vs. 7.6 +/- 1.9 ml.min-1 x W-1, P < 0.01), and the phase lag
      increased above- compared with below-LAT work rate. VO2/heart rate fluctuations
      were dramatically reduced, whereas heart rate amplitude decreased and phase lag
      increased, for above-LAT sinusoidal work rate changes. These results suggest that
      VO2 kinetics are slowed in the work rate domain above the LAT relative to that
      below the LAT and that VO2 kinetics could be limited by the O2 transport
      mechanisms to the exercising muscle.

PMID- 8282621
TI  - Effect of 8 wk of bicycle training on the immune system of patients with
      rheumatoid arthritis.
AB  - The effect of 8 wk of progressive bicycle training on the immune system was
      evaluated in a controlled study on 18 patients with rheumatoid arthritis and
      moderate disease activity. Maximal O2 uptake increased significantly, whereas
      heart rate at stage 2 and rate of perceived exertion decreased significantly, in
      the training group compared with the controls. Resting levels of a number of
      immune parameters were measured before and after 4 and 8 wk of training. Training
      did not induce changes in blood mononuclear cell subpopulations, proliferative
      response, or natural killer cell activity. Furthermore the plasma concentrations
      of interleukin-1 alpha, interleukin-1 beta, and interleukin-6 did not change in
      response to training. It is concluded that 8 wk of bicycle training does not
      influence the immune system of patients with rheumatoid arthritis.

PMID- 8282622
TI  - Human red blood cell aging at 5,050-m altitude: a role during adaptation to
      hypoxia.
AB  - To test the hypothesis that the human red blood cell aging process participates
      actively in the adaptation to hypoxia, we studied some physical and biochemical
      hematologic variables in 10 volunteers at sea level (SL) and after 1 (1WK) or 5
      wk (5WK) of exposure to 5,050-m altitude. The 2,3-diphosphoglycerate-to
      hemoglobin ratio (2,3-DPG/Hb) was 0.88 +/- 0.03 (mol/mol) at SL and increased to
      1.08 +/- 0.03 (P = 0.002) and 1.28 +/- 0.05 (P < 0.0001) at 1WK and 5WK,
      respectively. The average red blood cell density (D50), which is inversely
      proportional to the fraction of young red blood cells and is therefore an index
      of the red blood cell aging process, was 1.1053 +/- 0.0007 g/ml at SL and
      decreased to 1.1046 +/- 0.0008 g/ml (NS) and 1.1018 +/- 0.0008 g/ml (P < 0.001)
      at 1WK and 5WK, respectively. D50 was correlated with 2,3-DPG/Hb at SL (P =
      0.004), only weakly at 5WK (P = 0.1), but not at all at 1WK. The arterial O2
      saturation was correlated with the change of 2,3-DPG/Hb in 1WK (P = 0.02) and
      that of D50 in 5WK (P = 0.04). It is concluded that short-term (1WK) increase of
      2,3-DPG/Hb is not associated with the erythropoietic response but is presumably
      due to respiratory alkalosis. By contrast, after prolonged hypoxia (5WK),
      erythropoiesis may provide an efficient way for increasing blood 2,3-DPG through
      an augmented proportion of young red blood cells.

PMID- 8282623
TI  - Morphometry of methacholine-induced bronchoconstriction in the rat.
AB  - It has been suggested that parenchymal viscoelasticity accounts for a large
      proportion of resistive pressure losses induced by smooth muscle agonists. We
      used morphometric methods to evaluate the relative contributions of parenchyma
      and airways to mechanical changes during methacholine- (MCh) induced
      bronchoconstriction. We measured tracheal pressure and tidal volume in 17 open
      chest mechanically ventilated Sprague-Dawley rats (frequency = 1.5 Hz, tidal
      volume = 2 ml, positive end-expiratory pressure = 5 cmH2O) after saline (n = 7,
      C), 16 mg/ml MCh (n = 5, L), and 256 mg/ml MCh (n = 5, H) aerosols. We calculated
      pulmonary resistance (RL) and elastance (EL) by fitting the equation PL = VRL +
      VEL + K, where PL is transpulmonary pressure, V is flow, and V is volume. V was
      obtained numerically from V. Lungs were rapidly frozen in liquid N2 30 s after
      aerosolization and processed with freeze substitution. Using midsagittal slices
      of left lung, we measured airway narrowing as the ratio of lumen area (aBM)
      subtended by the basement membrane perimeter (LBM) to predicted maximal lumen
      area (ABM = LBM2/4 pi). Air space size was estimated as mean linear intercept
      (Lm) and parenchymal distortion as standard deviation of linear intercepts (SDi).
      Lm was increased in L and H animals, reflecting hyperinflation; aBM/ABM in 0.17-
      to 0.43-mm-diam airways decreased progressively from C to L to H animals,
      reflecting bronchoconstriction. By use of stepwise multiple linear regression,
      the contribution of Lm to variance in mechanics was found to consistently exceed
      or equal that of aBM/ABM. SDi contributed little once Lm was taken into
      account.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282624
TI  - Partitioning of work of breathing in mechanically ventilated COPD patients.
AB  - In 10 sedated paralyzed mechanically ventilated chronic obstructive pulmonary
      disease (COPD) patients, we measured the inspiratory mechanical work done per
      breath on the respiratory system (WI,rs). We measured the tracheal and esophageal
      pressures to assess the lung (L) and chest wall (W) components of WI and used the
      technique of rapid airway occlusion during constant-flow inflation to partition
      WI into static work [Wst, including work due to intrinsic positive end-expiratory
      pressure (WPEEPi)], dynamic work due to airway resistance, and the additional
      resistance offered by the respiratory tissues. Although the patients were
      hyperinflated, the slope of the static volume-pressure relationships of the lung
      did not decrease with inflation volume up to 0.8 liter. WI,W was similar in COPD
      patients and normal subjects. All components of WI,L were higher in COPD
      patients. The increase in Wst,rs was due entirely to WPEEPi. Our data suggest
      that, during spontaneous breathing, COPD patients would probably develop
      inspiratory muscle fatigue, unless continuous positive airway pressure were
      applied to reduce WPEEPi.

PMID- 8282625
TI  - Expiratory airflow limitation and hyperinflation during methacholine-induced
      bronchoconstriction.
AB  - To investigate the role of airflow limitation on the increase of end-expiratory
      lung volume (EELV) during bronchoconstriction, nine stable asthmatic subjects and
      seven healthy subjects were challenged with inhaled methacholine (MCh). Changes
      in airway caliber were assessed by using forced expiratory volume in 1 s, partial
      forced expiratory flow at 50% of control forced vital capacity, and specific
      airway conductance. To detect airflow limitation, tidal flow-volume curves were
      superimposed on partial forced flow-volume curves at absolute lung volume. The
      electromyogram of the diaphragm was recorded by surface electrodes in four
      asthmatic and four healthy subjects, and the electrical diaphragmatic activity
      (DIA) during expiration was expressed as a percentage of the duration of
      expiratory time. In 10 subjects (9 asthmatic and 1 healthy) the partial forced
      expiratory flow recorded after some MCh dose impinged on tidal expiratory flow
      recorded before MCh. When this occurred it was associated with an increase in
      EELV by 0.54 +/- 0.07 (SE) liter (P < 0.001), which was larger than that
      occurring when lower MCh doses (0.11 +/- 0.04 liter, P < 0.05) were used, and
      with a moderate increase in DIA of 15 +/- 2.5% (P < 0.01). Six healthy subjects
      did not increase EELV after MCh despite a significant degree of
      bronchoconstriction; in these subjects tidal expiratory flow never impinged on
      forced expiratory flow, and DIA never increased. These results suggest that
      hyperinflation during MCh-induced bronchoconstriction is triggered by dynamic
      compression of the airways and is associated with moderate increase of DIA during
      expiration.

PMID- 8282626
TI  - Tracheobronchial dilation during isocapnic hypoxia in conscious humans.
AB  - To assess the effects of isocapnic hypoxia on the pharynx, glottis, extrathoracic
      trachea (ET), intrathoracic trachea (IT), and main bronchi (MB), we measured the
      cross-sectional areas of these airways by acoustic reflection technique in 15
      healthy volunteers. Measurements were made during tidal volume breathing while
      subjects were normoxic [arterial O2 saturation (SaO2) > 95%] or were made hypoxic
      by a rebreathing procedure. Under hypoxemic conditions, airway cross-sectional
      areas increased significantly at ET, IT, and MB levels (P < 0.001). The magnitude
      of this dilation was similar for both levels of hypoxemia studied (SaO2 80-85%
      and 70-75%); at the milder of the two hypoxemic conditions, ET cross-sectional
      area increased by 12.4 +/- 4.2% (SE), IT by 10.2 +/- 5.9%, and MB by 19.1 +/-
      3.2%. No significant changes were found in the pharyngeal or glottic areas.
      Dilation was not produced by normoxic isocapnic hyperventilation, and the use of
      hypoxic airway gas mixtures did not artifactually alter acoustic reflection
      measurements in a mechanical model. Vagal airway tone, as reflected by airway
      constriction during pauses in tidal breathing, was unaffected by isocapnic
      hypoxia. We conclude that isocapnic hypoxia produces dilation of the trachea and
      major bronchi, an effect unaccounted for by an alteration in the ventilatory
      pattern.

PMID- 8282627
TI  - Influence of diffusion on estimations of protein reflection coefficient by double
      indicator method.
AB  - In isolated perfused organs, vascular protein reflection coefficients (sigma) can
      be calculated from the changes in hematocrit and perfusate protein concentration
      (CP) that occur during edema formation. This technique requires the assumption
      that transvascular protein flux by diffusion is negligible. To assess diffusion
      induced errors in calculations of sigma, we derived an expression for CP that
      includes determinants of diffusive protein flux: protein permeability-surface
      area product (PS), transvascular fluid flux (J), true sigma, and transvascular
      protein concentration. We used this expression to obtain values of CP under
      various experimental conditions and then calculated values of sigma (measured
      sigma) for those conditions. Diffusion causes measured sigma to be lower than
      true sigma. The diffusion-induced error is larger and potentially substantial
      when J/PS is low and when true sigma is high. Diffusion-induced error is also
      larger when the amount of edema formation is greater. In recent isolated canine
      lung experiments where J/PS was approximately 2.7, diffusion-induced errors in
      measured sigma for albumin would have been approximately 0.06 (at true sigma =
      0.5) and approximately 0.18 (at true sigma = 0.9). When J/PS was higher, the
      potential for diffusion-induced errors was much smaller. We conclude that
      diffusion causes underestimation of true sigma and that the error in measured
      sigma may be substantial when J/PS is < 5 and when true sigma is > 0.5.

PMID- 8282628
TI  - Regional blood volume distribution during positive and negative airway pressure
      breathing in supine humans.
AB  - To assess the effects of continuous positive (CPAP) or negative airway pressure
      (CNAP) breathing (+/- 10-12 cmH2O, duration 25 min) on blood content in the
      body's capacitance vasculature, regional distribution of labeled red blood cells
      was evaluated in seven spontaneously breathing supine volunteers. Counts were
      acquired by whole body scans and detectors overlying the liver, intestine, left
      ventricle, and lower arm, and arterial pressure, heart rate, calf blood flow and
      vascular resistance, hematocrit, vasopressin, and atrial natriuretic peptide
      plasma concentrations were also obtained. With CPAP, thoracic, cardiac, and left
      ventricular counts diminished significantly by 7-10%, were accompanied by
      significant increases in counts over both the gut and liver, and remained
      decreased during CPAP but reversed to baseline with zero airway pressure. Calf
      blood flow and vascular resistance significantly decreased and increased,
      respectively, whereas limb counts, arterial pressure, heart rate, and hormone
      concentrations remained unchanged. With CNAP, in contrast, regional counts and
      other variables did not change. Thus, moderate levels of CPAP deplete the
      intrathoracic vascular bed and heart, shifting blood toward the gut and liver but
      not toward the limbs. No short-term compensation increasing cardiac filling
      during CPAP was seen. In contrast, CNAP did not alter intrathoracic or organ
      blood content and, therefore, does not simply mirror the effects evoked by CPAP.

PMID- 8282629
TI  - Muscle fiber type composition and fiber size in successfully and unsuccessfully
      endurance-raced horses.
AB  - Triplicate biopsies from three different depths of the gluteus medius muscle were
      obtained in 36 endurance-raced horses, aged 8.42 +/- 2.85 yr. Twenty of the
      horses were considered excellent endurance performers according to the mean speed
      of their three fastest records in endurance events for the past 2 or 3 years,
      whereas 16 were moderate performers, with a mean racing speed < 12.5 km/h (in 120
      to 180-km endurance rides), < 14 km/h (in 80- to 120-km endurance rides), or <
      13.5 km/h (in 40- to 60-km endurance rides). Significant differences in muscle
      fiber type composition and fiber size were recorded; excellent performers had a
      higher percentage and a larger size of type I and type IIa fibers (high and low
      myosin adenosinetriphosphatase activity at pH 4.5, respectively) and a lower
      percentage of type IIb fibers (moderate myosin adenosinetriphosphatase activity
      at pH 4.5), including both type IIb oxidative (moderate to high NADH-tetrazolium
      reductase activity) and IIb nonoxidative (low NADH-tetrazolium reductase
      activity). The differences in distribution of myofiber types and in fiber sizes
      were more marked in the deeper parts compared with the superficial regions of
      muscle. Our results also imply a greater homogeneity among the fiber type sizes
      across the muscle in horses with a superior endurance performance than in horses
      that had been poorly or moderately endurance raced. Thus the results show that
      fiber type proportions and fiber size in equine skeletal muscle are directly
      related to the athletic ability of the horse for endurance events.

PMID- 8282630
TI  - Correlations between flow resistance and geometry in a model of the human nose.
AB  - The relationship between the pressure losses within the nasal airways and nasal
      geometry were studied in a 3:1 scale model. The geometry of the model was based
      on magnetic resonance images of the skull of a healthy male subject. Pressure
      measurements, flow visualization, and hot-wire anemometry studies were performed
      at flow rates that, in vivo, corresponded to flows of between 0.05 and 1.50 l/s.
      The influence of nasal congestion and the collapse of the external nares were
      examined by using modeling clay to simulate local constrictions in the cross
      section. A dimensionless analysis of the pressure losses within three sections of
      the airway revealed the influence of various anatomic dimensions on nasal
      resistance. The region of the exterior nose behaves as a contraction-expansion
      nozzle in which the pressure losses are a function of the smallest cross
      sectional area. Losses in the interior nose resemble those associated with
      channel flow. The nasopharynx is modeled as a sharp bend in a circular duct. Good
      correspondence was found between the predicted and actual pressure losses in the
      model under conditions that stimulated local obstructions and congestion.

PMID- 8282631
TI  - Estimating body composition of young children by using bioelectrical resistance.
AB  - It is currently unclear whether age-specific equations should be used for
      assessing body composition from bioelectrical resistance. Kushner et al. (Am. J.
      Clin. Nutr. 56: 835-839, 1992) showed that the relationship between
      height2/resistance and total body water (TBW) is robust across a wide age range,
      although uncertainty remained over the relationship in preschool children. We
      therefore cross-validated the Kushner equation for predicting total body water in
      4- to 6-yr-old children in two independent laboratories. TBW was measured from H2
      18O dilution, and bioelectrical resistance and reactance were measured using an
      RJL 101A analyzer in 31 children (15 females, 16 males; 5 +/- 0.8 yr) studied in
      Burlington, Vermont, and 30 children (14 females, 16 males; 5 +/- 0.2 yr) studied
      in Phoenix, Arizona. There was no significant difference between TBW predicted
      from the Kushner equation and that measured in children in Burlington (11.76 +/-
      2.00 vs. 11.91 +/- 2.46 kg; r = 0.94) or in Phoenix (11.53 +/- 1.64 vs. 11.66 +/-
      1.90 kg; r = 0.94). The Kushner equation for TBW can be transformed into an
      equation for fat-free mass (FFM) by using published age- and gender-specific
      constants for the hydration of FFM: hydration of FFM = 76.9 - 0.25 age (yr) - 1.9
      gender where female equals 0 and male equals 1. The intraclass reliability for
      estimates of fat mass and FFM with the use of bioelectrical resistance in an
      independent group of 26 children (5.0 +/- 0.8 yr, 20.2 +/- 3.0 kg) was > 0.99 for
      duplicate observations performed 2 wk apart.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282632
TI  - Effect of hypercapnia and hypoxia on arytenoideus muscle activity in normal adult
      humans.
AB  - The electrical activity of the arytenoideus muscle, a vocal cord adductor, was
      measured in 14 normal adult humans during progressive isocapnic hypoxia and
      progressive hyperoxic hypercapnia. Electromyograms of the arytenoideus were
      obtained with intramuscular hooked-wire electrodes implanted by means of a fiber
      optic nasopharyngoscope. Correct placement of the electrodes was confirmed by
      discharge patterns during voluntary maneuvers. In three of the subjects,
      respiratory-related arytenoideus activity was not present during quiet breathing
      or chemical stimulation. During quiet breathing in the 11 other subjects, the
      arytenoideus exhibited phasic activity during expiration and usually tonic
      activity throughout the respiratory cycle. Phasic and tonic arytenoideus activity
      decreased under hypoxic and hypercapnic conditions. At higher levels of chemical
      stimulation in many subjects, short abrupt bursts of activity were frequently
      present at the transitions between inspiration and expiration. To determine the
      mechanical effect of the latter electromyographic findings, arytenoideus activity
      and fiber-optic images of the glottic aperture were simultaneously recorded in
      nine additional normal adult human subjects during progressive hyperoxic
      hypercapnia. The short abrupt bursts of arytenoideus activity were usually
      associated with a decrease in glottic aperture, although no change and an
      increase in glottic aperture were observed in individual subjects. The results
      suggest that the arytenoideus muscle may have an important role in the control of
      ventilation in normal human subjects.

PMID- 8282633
TI  - Adequacy of food rations in soldiers during an arctic exercise measured by doubly
      labeled water.
AB  - To investigate the adequacy of food rations to supply energy needs in cold
      temperature environments, caloric expenditure and intake and body composition
      changes were measured in a group of infantrymen during a 10-day field exercise in
      the Canadian Arctic. Energy expenditure was measured by the doubly labeled water
      method (n = 10), and caloric intake was measured by complete food intake records
      (n = 20). Body composition was determined by isotope dilution (n = 10) and
      bioelectrical impedence analysis (n = 20) on days 0 and 10. Baseline isotopic
      enrichment shifts due to geographical relocation were also monitored (n = 5).
      Mean body weight decreased 0.63 +/- 0.83 (SD) kg over the study period (P <
      0.005), although fat-free and fat mass compartment changes were not significant.
      Baseline isotopic changes were -4.65 +/- 2.54 and -0.48 +/- 0.07 /1000/day for
      deuterium and 18O, respectively. Mean baseline corrected energy expenditure level
      was 4,317 +/- 927 kcal/day. Self-reported caloric intakes obtained from food
      records were 2,633 +/- 499 kcal/day (61.0% of expenditure). Rations packs
      contained 4,350 kcal/day. Results suggest that 1) food intake was significantly
      underreported and 2) the energy needs of most subjects were being met by rations
      and available supplements.

PMID- 8282634
TI  - Model of pleural fluid turnover.
AB  - A model of pleural fluid turnover, based on mass conservation law, was developed
      from experimental evidence that 1) pleural fluid filters through the parietal
      pleura and is drained by parietal lymphatics and 2) lymph flow increases after an
      increase in pleural liquid volume, attaining a maximum value 10 times greater
      than control. From the differential equation describing the time evolution of
      pleural liquid pressure, we obtained the equation for the steady-state condition
      ("set point") of pleural liquid pressure: Pss = (KfPi*+KlPzf)/Kf+Kl), where Kf is
      parietal pleura filtration coefficient, Kl is initial lymphatic conductance, Pzf
      is lymphatic potential absorption pressure, and Pi* is a factor accounting for
      the protein reflection coefficient of parietal mesothelium and hydraulic and
      colloid osmotic pressure of parietal interstitium and pleural liquid. Lymphatics
      act as a passive negative-feedback control tending to offset increases in pleural
      liquid volume. Some features of this control are summarized here: 1) lymphatics
      exert a tight control on pleural liquid volume or pressure so that the set point
      is maintained close to the potential absorption pressure of lymphatics; 2) a 10
      fold increase in Kf would cause only a 2- and 5-fold increase in pleural liquid
      volume with normal (1.8 g/dl) and increased (3.4 g/dl) protein concentration of
      the pleural fluid, respectively; and 3) the reduction in maximum lymph flow
      greatly reduces the range of operation of the control with increased filtration
      and/or protein concentration of pleural fluid.

PMID- 8282635
TI  - Persistent peripheral vasodilation and sympathetic activity in hypotension after
      maximal exercise.
AB  - Hemodynamics (by aortic Doppler), autonomic factors (power spectrum analysis of
      heart rate and blood pressure variabilities and baroreceptor sensitivity), and
      plasma renin activity during the hypotension after maximal exercise were studied
      in 10 normal subjects on two separate days: a nonexercise (control) day (30 min
      of upright rest followed by 60 min of supine rest) and an exercise day (maximal
      upright bicycle exercise followed by 60 min supine) in random order. After
      exercise, diastolic pressure was reduced for the entire hour, cardiac output
      increased (+33.8%, P < 0.05), stroke volume was unchanged, and systemic vascular
      resistance fell (-28.6%, P < 0.01). Indexes of vagal activity were reduced for 60
      min, whereas the sympathetic indexes were elevated. Baroreflex sensitivity was
      also reduced for the first 10 min after exercise. Renin activity increased
      threefold after exercise. The postexercise hypotension results from a persisting
      peripheral vasodilation despite an increase in renin activity: the persistent
      sympathetic activity and reduced vagal tone are probably reflex responses to this
      vasodilatation.

PMID- 8282636
TI  - Interaction among cardiac, respiratory, and locomotor rhythms during
      cardiolocomotor synchronization.
AB  - The nature of entrainment between cardiac and locomotor rhythms was investigated
      while normal human subjects walked or ran on a treadmill. To detect the incidence
      of entrainment occurrence, the phase relationships among cardiac, respiratory,
      and locomotor rhythms were analyzed. The phase relationship between heartbeats
      and gait signals showed that entrainment of cardiac rhythm to locomotor rhythm
      occurred in all subjects at one or more treadmill speeds. To elucidate
      interactions among cardiac, respiratory, and locomotor rhythms during the
      cardiolocomotor synchronization, spectral and coherence analyses were done for
      these three rhythms. Spectral and coherence analyses on fluctuations in the heart
      period and respiratory rhythms revealed that the strength of coupling between
      cardiac and respiratory rhythms decreased in the presence of cardiolocomotor
      synchronization. In addition, the coupling of cardiac and locomotor rhythms
      appeared to induce dissociation of coupling between respiratory and locomotor
      rhythms. These results were similar to those observed when stepping was
      voluntarily synchronized with cardiac rhythm. Possible mechanisms to explain
      coordination and interaction among the neural oscillators innervating these three
      rhythms are discussed.

PMID- 8282637
TI  - Superior fatigue resistance of elite black South African distance runners.
AB  - Black athletes currently dominate long-distance running events in South Africa.
      In an attempt to explain an apparently superior running ability of black South
      African athletes at distances > 3 km, we compared physiological measurements in
      the fastest 9 white and 11 black South African middle-to long-distance runners.
      Whereas both groups ran at a similar percentage of maximal O2 uptake (%VO2max)
      over 1.65-5 km, the %VO2max sustained by black athletes was greater than that of
      white athletes at distances > 5 km (P < 0.001). Although both groups had similar
      training volumes, black athletes reported that they completed more exercise at >
      80% VO2max (36 +/- 18 vs. 14 +/- 7%: P < 0.005). When corrections were made for
      the black athletes' smaller body mass, their superior ability to sustain a high
      %VO2max could not be explained by any differences in VO2max, maximal ventilation,
      or submaximal running economy. Superior distance running performance of the black
      athletes was not due to a greater (+/- 50%) percentage of type I fibers but was
      associated with lower blood lactate concentrations during exercise. Time to
      fatigue during repetitive isometric muscle contractions was also longer in black
      runners (169 +/- 65 vs. 97 +/- 69 s; P < 0.05), but whether this observation
      explains the superior endurance or was due to the lower peak muscle strength
      (46.3 +/- 10.3 vs. 67.5 +/- 18.0 Nm/l lean thigh volume; P < 0.01) remains to be
      established.

PMID- 8282638
TI  - Effects of age, adiposity, and fitness level on plasma catecholamine responses to
      standing and exercise.
AB  - The plasma norepinephrine (NE) and epinephrine (E) responses to a variety of
      stressors are influenced by age, adiposity, and exercise training status. The
      objectives of this study were to 1) compare basal levels as well as posture- and
      exercise-induced changes in plasma NE and E concentrations in young [25 +/- 1
      (SE) yr; n = 24] and older (64 +/- 1 yr; n = 106) people and examine the
      associations of the responses with adiposity and maximal O2 uptake (VO2max) and
      2) determine the extent to which the NE and E responses are altered by exercise
      training in older people. We found no significant differences in basal NE and E
      levels between young and older subjects. However, the NE response to standing was
      exaggerated in older people (696 +/- 39 vs. 512 +/- 61 pg/ml; P < 0.05), whereas
      NE and E responses to exercise requiring approximately 78% of VO2max were
      attenuated in older people (NE: 1,444 +/- 74 vs. 1,983 +/- 222 pg/ml; E: 109 +/-
      10 vs. 228 +/- 29 pg/ml; both P < 0.01). Increments in NE and E during exercise
      were more closely associated with age (NE: r = -0.38; E: r = -0.46; both P <
      0.05) and VO2max (NE: r = 0.43; E: r = 0.52; both P < 0.05) than with adiposity
      (NE: r = -0.29; E: r = -0.25; both P < 0.05). In 48 older subjects who completed
      9 mo of exercise training, the increases in NE and E during exercise at the same
      absolute intensity were 39 and 57% lower, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8282639
TI  - Effect of ventilation frequency and tidal volume on pleural space thickness in
      rabbits.
AB  - The thickness of the pleural space was measured by fluorescence video-microscopy
      during mechanical ventilation in anesthetized paralyzed rabbits. A transparent
      parietal pleural window was made in the fourth or sixth intercostal space near
      midchest by dissection of intercostal muscle and endothoracic fascia.
      Fluorescence-labeled (fluorescein isothiocyanate) dextran solution (1 ml) was
      injected into the pleural space via a rib capsule and allowed to mix with the
      pleural liquid. With the rabbit in the left lateral decubitus position and the
      pleural window superior, the light emitted from the pleural liquid through the
      pleural window was measured through the videomicroscope. Both ventilation
      frequency and tidal volume were varied. Pleural space thickness was determined by
      in vitro calibration of the pleural liquid at the end of the experiment. At a
      frequency of 40 breaths/min and a tidal volume of 20 ml, pleural space thickness
      averaged 35 +/- 15 (SD) microns (n = 7). When frequency was reduced to 8
      breaths/min, this value was reduced by 40% to 22 +/- 11 microns. A reduction in
      tidal volume from 20 to 6 ml at a frequency of 40 breaths/min produced a similar
      reduction in pleural space thickness. During apnea, pleural space thickness
      averaged 11 +/- 3 microns. Cardiogenic motion had no measurable effect on pleural
      space thickness. The increased pleural space thickness with ventilation might
      serve to reduce the power dissipated due to sliding of the lung relative to the
      chest wall. Results support the concept of lubrication as the primary function of
      the pleural space.

PMID- 8282640
TI  - Dynamic multichannel near-infrared optical imaging of human brain activity.
AB  - The present paper demonstrates functional brain mapping with an optical imaging
      technique by using tissue-transparent near-infrared light. With a maximal five
      channel optical monitoring system, we succeeded in detecting region-specific
      changes in both the hemoglobin oxygenation state and blood volume during various
      mental tasks, in addition to visual and auditory stimulation. The time course of
      increases in blood supply varied with each brain region and depended on the type
      of internal operations occurring during the mental tasks. Changes in the
      hemoglobin oxygenation state were also different from region to region. This
      showed that there were regional variations of the oxygen delivery-oxygen
      utilization relationship during activation of brain activity. The usefulness of
      multichannel near-infrared functional imaging was well documented.

PMID- 8282641
TI  - Effect of acute resistance exercise on postexercise energy expenditure and
      resting metabolic rate.
AB  - Two separate experiments were performed to determine the effect of acute
      resistive exercise on postexercise energy expenditure in male subjects previously
      trained in resistive exercise. In experiment 1, after measurement of their
      resting metabolic rate (RMR) at 0700 h and their ingestion of a standardized meal
      at 0800 h, seven subjects (age range 22-40 yr) beginning at 1400 h completed a 90
      min weight-lifting protocol. Postexercise metabolic rate (PEMR) was measured
      continuously for 2 h after exercise and compared with a preexercise baseline. RMR
      was measured the following morning 15 h after completion of the workout. In
      experiment 2, six different men (age range 20-35 yr) completed a similar
      experimental protocol as well as a control condition on a separate day in which
      metabolic rate was measured for 2 h after a period of quiet sitting. For both
      experiments, PEMR remained elevated for the entire 2-h measured recovery period,
      with the average oxygen consumption for the last 6 min elevated by 11-12%. RMR
      measured the morning after exercise was 9.4% higher in experiment 1 and 4.7%
      higher in experiment 2 than on the previous day. In experiment 2, the
      postabsorptive respiratory exchange ratio was significantly lower the morning
      after the exercise bout. Strenuous resistive exercise may elevate PEMR for a
      prolonged period and may enhance postexercise lipid oxidation.

PMID- 8282643
TI  - New roles that mathematical modeling is filling in advanced physiological
      research.

PMID- 8282642
TI  - Micropipette and vascular occlusion pressures in isolated lungs of newborn lambs.
AB  - We compared measurements made by vascular occlusion, double occlusion, and
      micropuncture techniques in isolated perfused lungs of 3- to 10-day-old lambs.
      After adding indomethacin to the perfusate of 16 lungs, we used the micropuncture
      technique to measure pressures in 20- to 80-microns-diam arterioles (Pa80), 20-
      to 50-microns-diam venules (Pv20), and 50- to 150-microns-diam venules (Pv150).
      The vascular occlusion and double occlusion techniques were used in these same
      lungs to measure inflow occlusion (Pao), outflow occlusion (Pvo), and double
      occlusion pressures (Pdo). In 14 other lungs without indomethacin added to the
      perfusate, we measured Pv20 and Pvo before and during alveolar hypoxia and/or
      before and after the addition of papaverine to the perfusate. In indomethacin
      treated lungs, Pao was greater than Pa80, Pvo equaled Pv20 and Pv150, and Pdo was
      the same as Pa80, Pv20, and Pv150. In lungs without indomethacin treatment, Pvo
      was less than Pv20 both before and during hypoxia but Pvo equaled Pv20 after
      papaverine was added to the perfusate. Thus, in indomethacin-treated lungs of
      newborn lambs, Pao reflected pressure in arteries > 80 microns diam, Pdo
      reflected pressure between 80-microns-diam arteries and 150-microns-diam veins,
      and Pvo was similar to pressure in veins both as small as 20 microns diam and as
      large as 150 microns diam. However, without indomethacin there was a gradient
      between Pvo and Pv20 both before and during hypoxia but not after vasomotor tone
      was reduced with papaverine. Thus, the correlation between Pvo and micropuncture
      pressure in Pv20 and Pv150 was not constant and appeared related to vasomotor
      tone.

PMID- 8282644
TI  - Gas exchange in a three-compartment lung model analyzed by forcing sinusoids of
      N2O.
AB  - A mathematical gas exchange model, using sinusoidal forcing functions of inert
      inspired gas (A. Zwart, R. C. Seagrave, and A. Van Dieren. J. Appl. Physiol. 41:
      419-424, 1976), has been extended by us to include dead space (VD), a single
      alveolar compartment (VA) perfused with blood flow (Qp), and a shunt (Qs). In
      this new work we use N2O as the indicator gas in the mathematical model and in
      the experimental studies, in low enough concentrations [<6% (vol/vol)] to avoid
      anesthetic effects. Mathematical relationships between the inspired and expired
      N2O gas partial pressures, the blood gas N2O partial pressures, and their
      variation with forcing frequency are derived for a continuous ventilation uptake
      and a conventional anesthetic gas distribution model. We show that these gas and
      blood gas N2O relationships give direct derivation of cardiorespiratory
      parameters such as VA, Qp, the dead space-to-total ventilation ratio (VD/VT), and
      the shunt-to-total blood flow ratio (Qs/QT) without altering the subject's
      oxygenation and that they are essentially free from recirculation effects at high
      forcing frequencies > or = 2 min-1. Theoretical results from the model are
      presented for a wide range of forcing frequencies between 2 x 10(-2) and 10 min-1
      (sinusoid periods 30-0.1 min), and these show that VA, Qp, and VD/VT can all be
      measured by N2O forcing frequencies > or = 1 min-1. We also present results from
      five animal studies, with an experimental inspired gas forcing frequency range of
      0.125 to 2 min-1, which show qualitative agreement with the predictions of the
      continuous ventilation model. During these animal studies both mass spectrometric
      N2O respiratory gas measurements and intravascular polarographic arterial and
      mixed venous blood N2O partial pressure measurements were made, and examples of
      these in vivo measurements are presented, together with examples of the
      calculations derived from them.

PMID- 8282645
TI  - Demonstration of pulmonary vascular perfusion by electron and light microscopy.
AB  - To estimate the fraction of dense pulmonary capillary network that is perfused
      under physiological conditions, we developed a new method for the demonstration
      of in vivo capillary perfusion by light and electron microscopy. Blood plasma was
      labeled by 8-nm colloidal gold particles coated with rabbit serum albumin. In
      anesthetized rabbits, 4-5 ml of this tracer were injected into the right atrium.
      Two and 15 min later, the circulation was interrupted by a snare around the
      heart, and the lung was fixed by instillation with glutaraldehyde. Gold particles
      were found in the plasma space of alveolar capillaries as well as in other
      organs. A random sample of thin sections studied by electron microscopy revealed
      that the entire capillary bed of the lung was perfused at least with plasma
      within 2 min after tracer infusion. Light microscopy of silver-enhanced sections
      showed areas with different staining intensities but no obviously unperfused
      capillaries. The concept of capillary recruitment, which would require a
      significant fraction of capillaries unperfused at rest, may have to be reassessed
      to consider time factors as well as the two-phase nature of blood; red blood
      cells and plasma may take different paths.

PMID- 8282646
TI  - Measurement of hemoglobin flow and blood flow by near-infrared spectroscopy.
AB  - A noninvasive method of measuring hemoglobin flow through an organ by near
      infrared spectroscopy (NIRS) is described that allows blood flow to be
      calculated. The method is derived from the Fick principle and uses a small change
      in arterial oxyhemoglobin concentration (brought about by a change in the
      fractional inspired O2 concentration) as an intravascular tracer. Changes in
      deoxyhemoglobin and oxyhemoglobin concentrations are quantified by monitoring
      variations in the absorption of near-infrared light in the organ, thus providing
      a measure of tracer accumulation. The tracer input function is calculated from
      the change in arterial O2 saturation, measured by pulse oximetry. The method was
      used to determine hemoglobin flow in the forearms of six healthy young adults on
      10 occasions. Forearm hemoglobin flow ranged from 22.5 to 82.6 mumol.l-1.min-1.
      Calculated forearm blood flow ranged from 1.01 to 4.01 ml.100 g-1.min-1. For
      comparison, forearm blood flow was measured by venous occlusion plethysmography,
      and the relation between flow calculated by NIRS (y) and plethysmography (x) was
      y = 0.93x + 0.30 (r2 = 0.95). The mean difference between the methods was 0.14
      ml.100 g-1.min-1. The technique may be widely applicable.

PMID- 8282647
TI  - Assessment of postpreservation rat lung function using a new model for extended
      venous reperfusion.
AB  - Understanding the physiological significance of biochemical events after lung
      preservation in rats has been hampered by the lack of a suitable model for
      physiological assessment. We have developed an ex vivo paracorporeal rat lung
      perfusion model that permits hemodynamic and gas exchange evaluation of lung
      function. After anesthesia and heparinization, the heart-lung block was removed
      and the left lung was reperfused for 1 h at a constant flow of 4 ml/min with
      homologous venous blood drained from the inferior vena cava of the paracorporeal
      (host) rat. The lung effluent was returned at the same flow rate to the host
      distal aorta. The model was validated by the assessment of lung function after
      room temperature ischemia. Animals were allocated into three groups (n = 6)
      according to the ischemic interval (group 1, 20 min; group 2, 3 h; group 3, 4 h).
      In groups 1 and 2, PO2, PCO2, mean airway pressure, and pulmonary arterial
      pressure were within the normal ranges and stable throughout the experiment. In
      contrast, lungs in group 3 demonstrated higher pulmonary arterial pressure and
      lower blood effluent PO2 than were found in either group 1 or 2. A significant
      weight gain during reperfusion was observed only in group 3 (4.23 +/- 0.9 g; P <
      0.002). For each lung, the final blood effluent PO2 correlated with the weight
      gain (R2 = 0.81; P < 0.0001). Our results indicate that this model can be used
      reliably to detect lung dysfunction after ischemic injury.

PMID- 8282648
TI  - Measuring circulating cytokines.
AB  - Cytokines, i.e., regulatory proteins derived primarily (but not exclusively) from
      cells of the immune system, are receiving increasing attention for their
      influences on physiological processes. This paper outlines several of the unique
      characteristics of cytokines and discusses the pitfalls encountered when
      measuring them in biological fluids. At present, each available assay has a
      combination of advantages and drawbacks; therefore, investigators must be aware
      of the trade-offs and choose the assay that best addresses their needs. The
      factors that affect cytokine measurement also influence cytokine activity in
      vivo; thus they are important from a physiological as well as methodological
      standpoint. Moreover, the absolute concentration of a single cytokine is probably
      less important than the balance between that cytokine and its natural
      antagonists.

PMID- 8282649
TI  - Validation of a volumeless breath-by-breath method for measurement of respiratory
      quotient.
AB  - Measurement of respiratory quotient (RQ) is useful as an indicator of changes in
      CO2 equilibrium or metabolism. Because of technical difficulties when volumetric
      or mixed expired methods are applied to clinical practice, we sought to validate
      a method of volumeless breath-by-breath RQ measurement based on real-time
      analysis of inspired and alveolar concentrations of O2, CO2, and N2 alone. We
      derived our volumeless method from a modified three-compartment lung model and
      tested the validity of the model by comparing it with a standard volumetric open
      circuit method. Data from 1,736 breaths from 25 healthy adult volunteers for a
      total of 78 epochs were collected. Inspired, end-tidal, and mixed expired gas
      compositions were analyzed by Raman spectroscopy, and RQ values from 0.6 to 2.4
      were obtained. Linear regression of the volumeless breath-by-breath method
      against the open-circuit method yielded a line with a slope of 1.002 (95%
      confidence interval 0.928 to 1.076) and an intercept of 0.066 (95% confidence
      interval -0.008 to 0.146) with an R2 of 0.91 (P < 0.001). We analyzed agreement
      by several methods and used mathematical modeling to predict precision with
      variations in epoch length and breath volume, which were verified by Monte Carlo
      techniques. We demonstrated that RQ can be measured reliably and easily using
      this volumeless breath-by-breath technique.

PMID- 8282650
TI  - High muscle blood flow in man: is maximal O2 extraction compromised?
AB  - During conventional cycle ergometry, as work rate (WR) is increased toward
      maximum, O2 extraction increases hyperbolically, typically achieving values of 80
      90% at peak O2 uptake (VO2). In contrast, studies using isolated knee-extensor
      exercise report much higher mass-specific blood flows (Q) and lower maximal O2
      extractions (approximately 70%), which have been interpreted as transit time
      limitation to O2 movement out of the muscle capillary. However, maximal
      achievable WR levels during conventional cycle ergometry are generally reached
      (over 10-15 min) after rapid increases in WR, whereas the reported knee-extensor
      studies have used only more lengthy protocols (45 min). The duration of these
      protocols may have prevented the attainment of high WR levels and thus high O2
      extraction ratios. Accordingly, this investigation examined leg Q and O2
      extraction responses during single-leg knee-extensor exercise incremented rapidly
      (steps of 15-25 W per 2- to 3-min interval), which produced fatigue in 13-15 min.
      Q and muscle VO2 increased linearly with WR to fatigue with Q-WR and VO2-WR
      slopes similar to those reported in previous knee-extensor studies. However, with
      the use of this protocol, very high maximal achievable WR [99 +/- 6 (SE) W] and
      muscle Q (385 +/- 26 ml.min-1 x 100 g-1) levels were attained, some 80% greater
      than previously reported. An O2 extraction of 84.6 +/- 2.1% was reached, giving a
      maximal VO2 of 60.2 +/- 5.8 ml.min-1 x 100 g-1. We conclude that, even under the
      high Q conditions of single-leg knee-extensor exercise, O2 extraction does not
      reach a plateau on the basis of short transit times and that previous conclusions
      to the contrary reflect failure to attain sufficiently high WR levels. Maximal
      VO2, Q, and O2 extraction in this model have yet to be defined.

PMID- 8282651
TI  - Role of vasopressin and atrial natriuretic factor in response to head-out water
      immersion.

PMID- 8282652
TI  - Michaelis-Menten enzymes and flux changes through metabolic pathways: a short
      lived paradox?

PMID- 8282653
TI  - Hemodynamic responses to exercise in blacks and whites.

PMID- 8282654
TI  - How can epidemiology improve mental health services for children and adolescents?
AB  - Epidemiology, the study of patterns of disease distribution in time and space,
      can help to improve mental health services for children and adolescents by
      increasing understanding of the causes, development, and course of psychiatric
      disorders. For the purpose of service delivery, epidemiologic research on child
      psychopathology can provide information on need for services, availability of
      services, and effectiveness of services. For both scientific and planning
      purposes, epidemiologic research can inform us about (1) the developmental course
      of psychiatric disorders during childhood and adolescence, (2) the effect of
      psychiatric disorder on the course of normal childhood development, and (3) the
      effect of childhood development on the developmental course of psychiatric
      disorder. Information about prevalence and incidence is useful for planning
      primary, secondary, and tertiary prevention and treatment services. The same
      information is scientifically useful to the extent that it helps to answer
      questions about causation, course, and outcome. However, one aim of this paper is
      to show that epidemiology is about a great deal more than rates of disorder.

PMID- 8282655
TI  - Mental health disorders from age 15 to age 18 years.
AB  - OBJECTIVE: To determine the strength of association between mental health
      disorders in adolescence and disorder in early adulthood. METHOD: The study used
      mental health data from a longitudinal investigation of a New Zealand birth
      cohort. Of the 943 with prevalence data for DSM-III disorder at age 15, 890 had
      prevalence data for DSM-III-R disorder when aged 18 years. RESULTS: Two-thirds of
      those with disorder at age 15 had disorder at age 18. The residual form of
      attention deficit disorder, simple phobias, and oppositional disorders (with no
      other accompanying disorders) were associated with the lowest risk of later
      disorder and conduct disorder with the highest. With the exception of the overall
      symptom level, a variety of characteristics examined (e.g., social competence and
      adversity) could not differentiate between those with transient disorder and
      those with disorder at both ages. Comparisons of those with recurring disorder
      and those with new disorder at age 18 showed that in addition to characteristics
      of the disorder, disadvantage was strongly associated with recurrent disorder.
      CONCLUSIONS: The risk of later disorder for those with disorder in adolescence
      was high and differed across type of disorder. Findings suggest that to reduce
      the risk of disorder in early adulthood, clinicians could play a more active role
      in community interventions with direct social outcomes.

PMID- 8282656
TI  - Prevalence and comorbidity of DSM-III-R diagnoses in a birth cohort of 15 year
      olds.
AB  - OBJECTIVE: To document the prevalence and comorbidities of a range of DSM-III-R
      diagnoses in a birth cohort of approximately 1,000 New Zealand children. METHOD:
      Parent and child reports were obtained on levels of DSM-III-R symptomatology in
      the child for five major groups of diagnoses: anxiety disorders, mood disorders,
      conduct/oppositional disorders, attention-deficit hyperactivity disorder, and
      substance abuse/dependence. Two methods, optimal informant and latent class
      modeling, were used to combine parent and child reports to produce a "best
      estimate" of the prevalence of disorder. RESULTS: Both methods produced very
      similar results. Overall approximately 25% of children met criteria for at least
      one DSM-III-R diagnosis. Rates of disorder were higher for girls (33%
      approximately) than for boys (20% approximately), this difference being largely
      owing to higher rates of anxiety and mood disorders among girls. There were
      strong tendencies for disruptive behavior and substance use disorders to cluster
      together and more diffuse tendencies for anxiety and mood disorders to be
      comorbid with each other and with other disorders. Only a minority (21%) of
      children with disorders were in contact with any service for their problems.
      CONCLUSION: These findings are consistent with a number of other studies of
      adolescent populations, both in terms of the prevalence of disorder and the
      comorbidities between disorders.

PMID- 8282657
TI  - Epidemiological comparisons of American and Dutch adolescents' self-reports.
AB  - OBJECTIVE: To determine the cross-cultural applicability of self-reports of
      adolescents' problems and competencies. METHOD: Youth Self-Reports (YSRs) were
      completed by 803 American and 803 Dutch nonreferred adolescents matched by
      gender, age, and socioeconomic status. RESULTS: Comparisons revealed that
      American adolescents reported many more problems than did Dutch adolescents. This
      finding contrasts sharply with the American/Dutch similarities in parents' and
      teachers' reports of children's problem behaviors. Competence scores also were
      much higher for the American than the Dutch sample. CONCLUSIONS: Cutpoints for
      discriminating the normal and the clinical range of YSR scores need to be
      adjusted to local norms for the Dutch sample. Cultural factors may be responsible
      for the cross-national differences.

PMID- 8282658
TI  - Are American children's problems getting worse? A 13-year comparison.
AB  - OBJECTIVE: To determine whether the prevalence of children's behavioral/emotional
      problems changed significantly over a 13-year period. METHOD: Problems and
      competencies reported by parents and teachers for a random sample of 7 to 16
      years old assessed in 1989 were compared with those reported by parents for a
      1976 sample and by teachers for a 1981 to 1982 sample. Parent reports were
      obtained with the Child Behavior Checklist; teacher reports were obtained with
      the Teacher's Report Form. RESULTS: Problem scores were higher and competence
      scores were lower in 1989 than in the earlier assessments. The secular changes
      were small but included diverse problems, syndromes, and competencies. Changes
      did not differ significantly by age, gender, socioeconomic status, nor
      black/white ethnicity. Correlations of 0.97 to 0.99 between rankings of item
      scores across 7.5- and 13-year intervals support the stability of the assessment
      procedures. Despite increases in problem scores, the 1989 U.S. scores were not
      higher than those in several other cultures. CONCLUSIONS: Viewed categorically in
      terms of caseness, more untreated children in the 1989 than the 1976 sample would
      be considered to need help. Multicohort longitudinal studies now in progress will
      test predictors of within- and between-cohort change.

PMID- 8282659
TI  - Psychosocial risks for major depression in late adolescence: a longitudinal
      community study.
AB  - OBJECTIVE: An ongoing 14-year longitudinal study examined psychosocial
      antecedents of major depression in late adolescence in a community population.
      METHOD: Subjects were 385 adolescents followed between the ages of 5 and 18
      years. Early health, familial, behavior, academic, and environmental risks for
      major depression were identified using data collected at ages 5, 9, 15, and 18
      years. At age 18, a lifetime diagnosis of major depression was assessed using the
      NIMH Diagnostic Interview Schedule (DIS-III-R). RESULTS: For males, neonatal
      health problems, dependence problems at age 5 years, perceived unpopularity and
      poorer perceptions of their role in the family at age 9 years, remarriage of a
      parent, early family discord, and anxiety at age 15 years significantly increased
      the risk of developing major depression. Females with major depression, compared
      with nondepressed females, had older parents and came from larger families, and
      at age 9 years had greater perceived unpopularity and anxiety, lower self-esteem,
      and poorer perceptions of their role in the family. Depressed females also
      reported more stressful life events, including death of parent and pregnancy.
      CONCLUSIONS: Underscoring the importance of early psychosocial factors in the
      later development of major depression and pointing to specific risks, our
      findings can aid in developing strategies for prevention and early intervention.

PMID- 8282660
TI  - Genetic studies of affective disorders: should we be starting with childhood
      onset probands?
AB  - OBJECTIVE: The objective of this study is to test whether the presence of
      childhood onset affective disorder identifies families with increased incidence
      and severity of affective disorders. METHOD: Family history information was
      collected on the first and second degree relatives and first cousins age > or =
      15 years of 22 children with bipolar affective disorder, 54 children with major
      depressive disorder, and 31 psychiatrically normal children. RESULTS: Compared
      with the relatives of normal children, relatives identified through children with
      bipolar affective disorder or major depressive disorder had elevated rates of
      affective disorders and increased severity of affective disorders as judged by
      earlier age of onset and increased suicide attempts. Segregation analyses could
      reject purely environmental transmission of illness. CONCLUSION: Ascertaining
      families through childhood onset affective disorder probands identifies extended
      pedigrees with high incidence and severity of affective disorders. These families
      may be more appropriate for genetic analyses than are families of adult probands.

PMID- 8282661
TI  - The quality of depression in adolescents with borderline personality disorder.
AB  - OBJECTIVE: The quality of depression in borderline adolescent girls was compared
      with the quality of depression in depressed, nonborderline girls. Psychoanalytic
      theories led us to expect signs of anaclitic depression in borderlines as well as
      a depressive sense of being "all bad." METHOD: Quality of depression was examined
      by means of Rorschach content analysis and the Depressive Experiences
      Questionnaire (DEQ). Borderline girls were expected to show greater Rorschach
      imagery pertaining to oral dependency and oral aggression than would depressed,
      nonborderline control girls. The borderline diagnosis was based on the Diagnostic
      Interview for Borderlines. DSM-III-R criteria were used to diagnose depression.
      Subjects were psychiatric inpatients, ages 14 to 18 years. RESULTS: As expected,
      it was found that borderline girls scored significantly higher than did controls
      on Rorschach scales of oral dependency; borderlines scored significantly higher
      on DEQ factors of dependency and self-criticism. Significant DEQ items reflected
      the borderlines' abandonment fears. CONCLUSIONS: This study provides empirical
      support for anaclitic depression in borderline adolescents, and suggests the
      presence of underlying fears in borderlines of being fundamentally evil or bad.

PMID- 8282662
TI  - Precipitant stressors in adolescent suicide.
AB  - OBJECTIVE: Precipitant stressors in adolescent (aged 13 to 19 years) suicides (N
      = 53) were investigated in a nationwide psychological autopsy study in Finland.
      METHOD: Data were collected through interviews with the victims' parents and
      health care personnel, and from official records. RESULTS: Precipitants during
      the month preceding suicide were found in 70% of the cases. Almost half the
      precipitants occurred during the last 24 hours. Interpersonal separations and
      conflicts were the most common precipitants. Compared with other suicide victims,
      those with weakened parental support more often had interpersonal separation as a
      precipitant, a higher number of stressors during the final month, and had more
      often experienced major stress during the year before suicide. CONCLUSION: The
      findings highlight the importance of stress (acute, chronic, or both) in
      adolescent suicide. Interpersonal problems were common precipitants in adolescent
      suicide. Among adolescents with weakened parental support, interpersonal
      separations were especially common precipitants. Additional research on
      precipitants in adolescent suicide is needed with proper control subjects.

PMID- 8282663
TI  - Adolescent witnesses to a peer suicide.
AB  - OBJECTIVE: This case-control study attempts to evaluate the psychological impact
      of witnessing a suicide on high school students. METHOD: Twenty-eight high school
      students witnessed a firearms suicide and the serious injury of another student
      while riding a school bus. They were assessed 2 months after the event, and their
      responses were compared with 28 demographically similar adolescents from another
      community who had not been exposed to suicide. RESULTS: The exposed students,
      when compared with the controls, had higher rates of new-onset anxiety disorder
      and a trend for increased rates of new-onset post-traumatic stress disorder
      (PTSD). Within the exposed group, measures of the closeness of the relationship
      to both the suicide victim and the student who was injured were correlated with
      the severity of PTSD symptomatology. Within the exposed group, other factors that
      predisposed to new-onset disorder included family history of affective illness,
      family history of suicide attempt, and stressful life events occurring in the
      year before exposure. CONCLUSIONS: In combination with the extant literature,
      this study demonstrates that adolescents who witness a traumatic suicidal death
      are at risk for the development of psychopathology, specifically, anxiety
      disorders and PTSD.

PMID- 8282664
TI  - Bereavement or depression? The impact of the loss of a friend to suicide.
AB  - OBJECTIVE: To determine whether the depressive reactions experienced by youth
      exposed to suicide were uncomplicated bereavement or bona fide major depression.
      METHOD: In a sample of 146 friends and acquaintances of 26 adolescent suicide
      victims, 43 (29%) developed a depressive episode subsequent to exposure to
      suicide, 18 were depressed before exposure, and 85 were never depressed. The
      three groups were compared. RESULTS: Those who became depressed after exposure
      were similar to those who were depressed before exposure. Both depressed groups
      differed from the nondepressed exposed group with respect to functional
      impairment, depressive symptom pattern and severity, convergent validity with
      other measures of depression, personal and family history of depression, and
      stressful life events. Previous depressives showed greater comorbidity with
      nonaffective disorders than those who became depressed after exposure. Those who
      became depressed after exposure compared with both the previous and nondepressive
      had a closer relationship with the suicide victims, showed more severe grief, and
      showed more intense exposure to the suicide. CONCLUSIONS: Depressive reactions
      occurring after exposure to suicide appear to be bona fide major depression,
      occurring as a complication of bereavement. Youth exposed to suicide should be
      carefully screened and followed up. Should a symptomatic picture of depression
      and functional impairment ensue, such exposed youth should be treated accordingly
      for a major depressive episode.

PMID- 8282665
TI  - Family functioning and suicidal behavior in adolescent inpatients with mood
      disorders.
AB  - OBJECTIVE: This study was designed to identify family and parental
      characteristics associated with suicidal behavior (active intent, gesture,
      attempt) among adolescent inpatients with mood disorders. METHOD: Subjects were
      32 suicidal adolescent inpatients with mood disorders, 32 nonsuicidal adolescent
      inpatients with mood disorders, and 38 normal comparison adolescents. A group
      comparison design was used. Adolescent measures were the Family Assessment Device
      and two semistructured interviews (Hamilton Rating Scale for Depression, Social
      Adjustment Inventory for Children and Adolescents). Parent measures were the
      Symptom Checklist-90 and the Social Adjustment Scale-Self Report. RESULTS:
      Fathers of suicidal adolescents reported more depression and family unit problems
      than did fathers of nonsuicidal and normal comparison adolescents, even after
      controlling for adolescents' depression severity. Suicidal adolescents, in turn,
      reported less active and communicative relationships with fathers. Differences
      among suicidal and nonsuicidal adolescents' perceptions of general family
      functioning were not significant after controlling for adolescents' depression
      severity. CONCLUSIONS: Findings highlight the importance of treating the
      depressed and potentially suicidal adolescent within the family system and
      attending to the nature and quality of adolescents' relationships with fathers as
      well as with mothers. Findings also highlight interactions between suicidal
      adolescents' depression severity and their negative perceptions of family
      functioning.

PMID- 8282666
TI  - Precursors of hyperactivity and aggression.
AB  - OBJECTIVE: This study investigated the early characteristics of children who at 8
      years old were hyperactive, aggressive, or both, to clarify the etiology of these
      disorders. METHOD: Prospective data from infancy to 8 years on children who were
      hyperactive (N = 65), aggressive (N = 57), or both (N = 60) at 8 years were
      compared with those on a normal comparison group (N = 70). Variables included
      ratings of temperament, behavior, school performance, and socioeconomic and life
      stress indices. RESULTS: The two aggressive groups, particularly the hyperactive
      aggressive group, were more difficult in temperament and behavior from infancy
      and had less optimal environments. In contrast, the "pure" hyperactive group
      showed more problems than did the comparison group only from 3 to 4 years on. All
      three clinical groups had poorer academic performance than did the controls.
      CONCLUSIONS: The findings are consistent with a transactional model of
      development in which aggression (with or without hyperactivity) emerges when
      difficultness in infancy interacts with a stressed environment. Hyperactivity,
      when unassociated with aggression, may emerge later from poor self-regulation
      when faced with societal, especially school, demands. The pattern of group
      differences found suggest that risk indicators for specific patterns of later
      maladjustment may be identifiable for early intervention.

PMID- 8282667
TI  - Testosterone and aggression in children.
AB  - OBJECTIVE: A link between serum testosterone and aggressive behavior, which has
      been demonstrated in numerous animal studies and suggested in several studies of
      adult men, has never been investigated in children before the time of puberty.
      METHOD: We measured serum testosterone, sex hormone binding globulin (SHBG),
      dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) in 18
      highly aggressive prepubertal boys, ages 4 to 10, hospitalized for violent or
      unmanageable behavior at a state children's psychiatric facility in New York City
      (the Bronx). We compared them with a group of age and race matched controls from
      the same demographic area, screened negative for aggressive behavior problems.
      All the aggressive subjects met DSM-III-R criteria for conduct disorder and
      scored higher than the 98th percentile on the aggression subscale of the Child
      Behavior Checklist (mean T = 80 for the group). RESULTS: There were no
      significant differences between aggressive and nonaggressive children for T,
      SHBG, DHEA, DHEAS, or ratios of combinations of these variables. CONCLUSIONS:
      These findings raise questions about inferences from adult studies that
      testosterone may play a causal role in the development of human aggression.
      Testosterone does not appear to be a useful biological marker for aggressivity in
      early childhood.

PMID- 8282668
TI  - Adolescent schoolboys in SED classes: implications for child psychiatry.
AB  - OBJECTIVE: The primary purpose of this study was to determine basic psychosocial
      characteristics for adolescent socially and emotionally disturbed (SED) boys.
      METHODS: Boys aged 12 to 16 years who were recommended for SED placement were
      compared with same-aged boys recommended for other educational intervention. The
      main measures were the Kiddie SADS-E interview and Achenbach's parent Child
      Behavior Checklist and Teacher Report Form scales. RESULTS: The adolescent SED
      boys were found to have normal intelligence, high rates of family stressors,
      predominantly DSM-III externalizing disorders, serious dysfunction according to
      checklist ratings by both teachers and parents, and little current community
      mental health intervention. They were significantly different from the comparison
      group on several variables: lower socioeconomic status, more abuse experience,
      greater diagnostic comorbidity, higher Axis V clinician ratings, and higher
      teacher ratings on externalizing scales. CONCLUSIONS: Findings are similar to
      those for other age-gender groups of SED students. One implication is the need
      for more private child psychiatrists to become involved in the collaborative
      treatment of this complex and seriously ill group of special education students.
      Consequently, a second implication is to increase the experience of child
      psychiatry trainees in dealing with the many consultative needs of SED students
      and staff.

PMID- 8282669
TI  - Persistent emotional disorder in children with neurological soft signs.
AB  - OBJECTIVE: This paper provides clinical details in the form of case vignettes
      from a prospective epidemiological study that found the combination of childhood
      "soft" signs and anxious behavior to be a strong risk factor for adolescent
      emotional disorders. METHOD: The original study conducted a neuropsychiatric
      assessment of adolescents who had been followed through childhood. RESULTS: The
      at-risk subjects are shown to exhibit a persistent and specific pattern of both
      motor abnormalities and anxiety, obsessional compulsive, or depressive symptoms
      over time. DISCUSSION: The form of their neurological and psychiatric
      abnormalities is consistent with neuropsychiatric research linking motor system
      abnormalities to emotional disorders. It is recommended that children who present
      with anxious and depressive symptoms be examined for motor soft signs.

PMID- 8282670
TI  - Psychological characteristics and DSM-III-R diagnoses at 6-year follow-up of
      adolescent anorexia nervosa.
AB  - OBJECTIVE: To examine the relationship between psychiatric disorder and
      psychological characteristics at 6-year follow-up of adolescent-onset anorexia
      nervosa. METHOD: Twenty-three subjects were interviewed by telephone using the
      Structured Clinical Interview for DSM-III-R diagnosis. These subjects and 23
      demographically similar controls completed standardized questionnaires that
      assessed their defense and coping styles, level of depression, defensiveness, and
      eating disorder psychopathology. RESULTS: Of the anorexic subjects 35% had no DSM
      III-R diagnosis, 43% an eating disorder, (9% anorexia nervosa, 17% bulimia
      nervosa, 22% eating disorder not otherwise specified), 30% an affective disorder,
      and 43% an anxiety disorder at follow-up. Factors at presentation associated with
      good outcome included greater use of mature defenses, less depression, and a
      lower drive for thinness. Psychological characteristics of anorexic subjects with
      good outcome resembled those of controls except that the former anorexics
      expressed greater dissatisfaction with their bodies and reported less use of
      cognitive avoidance as a coping mechanism. Anorexic subjects with continuing
      psychiatric problems differed from controls on most of the measures studied.
      CONCLUSIONS: Distribution of psychiatric disorders at follow-up is similar for
      adolescent and adult-onset anorexia nervosa. Self-report measures of some
      psychological characteristics are useful prognostic indicators. Absence of
      psychiatric disorder at follow-up is associated with normalization of many
      psychological characteristics.

PMID- 8282671
TI  - The relationship of caloric intake to frequency of dieting among preadolescent
      and adolescent girls.
AB  - OBJECTIVE: To assess the relationships of concern with weight and shape,
      frequency of dieting, body mass index (weight/height2), and energy intake among
      431 preadolescent and adolescent girls from a working-class New England suburb.
      METHOD: A cross-sectional study design used self-report measures of concern with
      weight, frequency of dieting, and average dietary intake. RESULTS: Approximately
      30% of the girls in each age stratum were above the national age-standardized
      85th percentile for body mass index (BMI). Body mass index was positively
      associated with concern about weight and shape (r = 0.46, p = 0.0001) and
      frequency of dieting (r = 0.49, p = 0.0001). Extreme concern with weight and
      shape was most common among the obese preadolescent and adolescent girls;
      however, dissatisfaction was also present among the underweight females. Fifty
      percent of the girls who were below the national age-standardized 15th percentile
      for BMI reported their ideal weight is less than their current weight, implying
      that among young women thinness is not adequate protection against
      dissatisfaction with weight and shape. Frequency of dieting was positively
      associated with concern about weight and shape (r = 0.53, p = 0.001) but not
      physical activity (r = -0.04, p = 0.36). Overall, we did not find strong evidence
      that dieters were eating less than their nondieting peers. Only among high school
      students was there a significant negative association between frequency of
      dieting and energy intake (r = -0.20, p = 0.01), suggesting that "dieting" may
      have a different meaning to preadolescents and adults. CONCLUSIONS: These
      findings indicate that self-reported frequent dieting in preadolescent and young
      adolescent girls is more indicative of extreme concern with weight than of
      decreased energy intake. Furthermore, extreme concern with weight and shape is
      most common among the obese preadolescent and adolescent girls.

PMID- 8282672
TI  - Possible association between fluoxetine hydrochloride and colic in an infant.
AB  - This is a case study of a 6-week-old infant referred for colic whose mother was
      using fluoxetine hydrochloride and breast feeding the infant. The mother switched
      to a commercial formula and reported a dramatic decrease in the infant's crying.
      We asked the mother to feed the infant breast milk from a bottle and she agreed.
      Throughout the study the mother kept a daily diary of her infant's crying,
      sleeping, stooling patterns, and feeding problems. Analysis of the mother's
      breast milk showed concentrations of 69 ng/mL for fluoxetine and 90 ng/mL for
      norfluoxetine. Infant blood serum/plasma level was analyzed for fluoxetine
      hydrochloride following return to breast milk. The concentrations were 340 ng/mL
      for fluoxetine and 208 ng/mL for norfluoxetine. The diary records showed
      increased crying, decreased sleep, increased vomiting, and watery stools when
      fluoxetine hydrochloride was transmitted through breast feeding or breast milk in
      bottle. These symptoms were reduced when the infant was formula fed. We suggest a
      possible relationship between colic and associated symptoms and fluoxetine
      hydrochloride in maternal breast milk.

PMID- 8282673
TI  - The etiology of autism: pre-, peri- and neonatal factors.
AB  - OBJECTIVE: To examine pre-, peri-, and neonatal factors in autism using composite
      optimality scores. METHOD: Pre-, peri-, and neonatal composite optimality scores
      were examined in 39 autistic subjects and 39 randomly matched sibling controls
      using a modification of the Gillberg Optimality Scale (Modified-GOS). Scores were
      based on best-estimate ratings of maternal interviews and medical records. Rules
      for best-estimate ratings were derived from a study of agreement between these
      two sources. RESULTS: Significant differences in optimality between autistic
      probands and their siblings were not present after adjustment for "maternal
      parity." Examination of specific variables revealed that only maternal parity
      differed significantly between autistic subjects and randomly matched sibling
      controls, reflecting an excess of first and fourth born among the autistic
      subjects. CONCLUSION: The findings of this study suggest that previous reports of
      an association between optimality and autism are a result of failure to adjust
      for birth order.

PMID- 8282674
TI  - Lack of cognitive impairment in first-degree relatives of children with pervasive
      developmental disorders.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that mild
      cognitive impairments aggregate in the unaffected first-degree relatives of
      probands with autism or pervasive developmental disorders (PDD). METHOD: The
      unaffected siblings and parents of 52 PDD probands and 33 Down syndrome and low
      birth weight controls were administered a battery of psychometric tests. The
      tests included measures previously found to be depressed in siblings of autistic
      children as well as cognitive deficits seen in PDD subjects of normal IQ. In
      addition, the Vineland Adaptive Behavior Scales were administered to siblings to
      measure the social-communication impairments found in PDD. RESULTS: Neither the
      siblings nor parents of the PDD probands demonstrated lower cognitive or adaptive
      behavior scores compared with controls. Developmental histories did not reveal
      greater rates of social, cognitive, or language delays, nor was there evidence to
      suggest that relatives of subgroups of PDD probands were different from each
      other. CONCLUSION: These findings indicate that, apart from relatives with PDD,
      cognitive and social impairments do not aggregate in the families of PDD
      probands.

PMID- 8282675
TI  - Developmental aspects of attachment behavior in young children with pervasive
      developmental disorders.
AB  - OBJECTIVE: The present study applied a continuous, clinically based rating system
      to compare predictions about attachment behavior in autism resulting from three
      different theoretical views and to characterize differences in attachment
      behavior of young autistic children. METHOD: The attachment behaviors of 32 young
      children with autism or pervasive developmental disorder were examined in a
      modified "strange situation." Attachment behaviors were rated on a continuous
      scale and on the Ainsworth subscales. Attachment ratings were compared with
      several developmental variables, including chronological age, mental age,
      language level, and social level. RESULTS: The continuous rating scale
      distinguished signs of security from signs of insecurity, allowing for behavioral
      idiosyncracies in the expression of attachment behavior seen in autistic
      children. The study found that 50% of the children demonstrated some behaviors
      indicative of secure attachment, that no children were unattached, and that
      developmental level rather than severity of autism was the strongest predictor of
      attachment security. CONCLUSIONS: Autism does not preclude the development of
      secure attachment relationships in young children, but rather it delays the
      development of secure attachment and may alter the behavioral patterns that
      express attachment security.

PMID- 8282676
TI  - Naltrexone in autistic children: behavioral symptoms and attentional learning.
AB  - OBJECTIVE: To assess critically the short-term efficacy and safety of naltrexone
      in autistic children and its effects on discrimination learning in the
      laboratory. METHOD: A parallel group design was employed. After a 2-week placebo
      baseline period, children were randomly assigned either to naltrexone or to
      placebo for a period of 3 weeks followed by a one-week posttreatment placebo
      period. Multiple raters and rating scales were employed in a variety of
      conditions. Forty-one children, all inpatients, ages 2.9 to 7.8 years, completed
      the study. Naltrexone reduced hyperactivity and had no effect on discrimination
      learning in the laboratory. There was a suggestion that it had a beneficial
      effect on decreasing self-injurious behavior. Untoward effects were mild and
      transient. CONCLUSION: In the present study, naltrexone significantly reduced
      only hyperactivity, and no serious untoward effects were observed. The
      effectiveness of naltrexone in the treatment of autism and self-injurious
      behavior requires additional assessment in a sample of children with moderate to
      severe self-injurious behavior.

PMID- 8282677
TI  - Autistic disorder and post-traumatic stress disorder.
AB  - The present case study examined an adolescent boy who initially was evaluated at
      our clinic and was found to meet DSM-III-R criteria for autistic disorder. After
      placement in a residential school using Daily Life Therapy for autistic disorder,
      the subject reported being physically abused by a staff member. Additional
      psychiatric evaluation revealed post-traumatic stress disorder (PTSD) including
      symbolic anxiety and repetition of the trauma. The diagnosis of PTSD should be
      considered in children with autistic disorder and other severe developmental
      disorders who have experienced physical and sexual abuse. Furthermore, parents,
      professionals, educators, and child care workers struggle with emotional
      reactions to children with severe developmental disorders and may have difficulty
      accepting the reality of the child rather than the fantasy of the "wished-for
      child." The disappointment of this fantasy and the equating of the child's
      weaknesses as one's own may lead to personal devaluation and increase the risk of
      abusive behavior.

PMID- 8282679
TI  - The case of the agreeable raters.

PMID- 8282678
TI  - An emerging schizophrenic syndrome.
AB  - This case history describes a 16-year-old adolescent male who developed
      schizophrenia with prominent negative symptoms. For the previous 6 years his
      diagnosis had been oppositional defiant disorder or conduct disorder. The
      clinical presentation, differential diagnosis, and management are discussed. The
      case exemplifies issues addressed in DSM IV.

PMID- 8282680
TI  - Risk and protective factors.

PMID- 8282681
TI  - Season of birth and dyslexia.

PMID- 8282682
TI  - TCA toxicity.

PMID- 8282683
TI  - The winds of (evolutionary) change: breathing new life into microbiology.

PMID- 8282684
TI  - Molecular characterization of the promoter of osmY, an rpoS-dependent gene.
AB  - The osmY gene, which encodes a periplasmic protein with an apparent M(r) of
      22,000, is induced by both osmotic and growth phase signals. We demonstrate here
      that osmY expression is regulated at the level of transcription and that
      transcription initiates 242 nucleotides upstream of the osmY open reading frame.
      Relative to the transcriptional start site, 5' deletions up to -36 did not
      inhibit osmY expression. 3' deletions that extended into the untranslated leader
      region affected the overall level of osmY::lacZ expression but did not affect
      inducibility. 5' and 3' deletions that extended past the transcriptional start
      region essentially abolished osmY expression, suggesting that there is a single
      promoter region. A putative promoter was identified, and its -10 region, TATATT,
      closely resembles the sigma 70 consensus -10 sequence, TATAAT. However, we show
      that osmY is not absolutely dependent on a functional sigma 70 for its
      expression. Since osmY expression does require rpoS (R. Hengge-Aronis, R. Lange,
      N. Henneberg, and D. Fischer, J. Bacteriol. 175:259-265, 1993), which encodes a
      stationary-phase sigma factor, sigma S (K. Tanaka, Y. Takayanagi, N. Fujita, A.
      Ishihama, and H. Takahashi, Proc. Natl. Acad. Sci. USA 90:3511-3515, 1993), E
      sigma S may be the form of RNA polymerase responsible for transcription of osmY.

PMID- 8282685
TI  - The nitrogen-regulated Bacillus subtilis nrgAB operon encodes a membrane protein
      and a protein highly similar to the Escherichia coli glnB-encoded PII protein.
AB  - Expression of beta-galactosidase encoded by the nrg-29::Tn917-lacZ insertion
      increases 4,000-fold during nitrogen-limited growth (M.R. Atkinson and S. H.
      Fisher, J. Bacteriol. 173:23-27, 1991). The chromosomal DNA adjacent to the nrg
      29::Tn917-lacZ insertion was cloned and sequenced. Analysis of the resulting
      nucleotide sequence revealed that the Tn917-lacZ transposon was inserted into the
      first gene of a dicistronic operon, nrgAB. The nrgA gene encodes a 43-kDa
      hydrophobic protein that is likely to be an integral membrane protein. The nrgB
      gene encodes a 13-kDa protein that has significant sequence similarity with the
      Escherichia coli glnB-encoded PII protein. Primer extension analysis revealed
      that the nrgAB operon is transcribed from a single promoter. The nucleotide
      sequence of this promoter has significant similarity with the -10 region, but not
      the -35 region, of the consensus sequence for Bacillus subtilis sigma A-dependent
      promoters.

PMID- 8282686
TI  - Determination of the growth rate-regulated steps in expression of the Escherichia
      coli K-12 gnd gene.
AB  - In Escherichia coli K-12 strain W3110, the amount of 6-phosphogluconate
      dehydrogenase relative to that of total protein, i.e., the specific enzyme
      activity, increases about threefold during growth in minimal media over the range
      of growth rates with acetate and glucose as sole carbon sources. Previous work
      with gnd-lac operon and protein fusion strains indicated that two steps in the
      expression of the gnd gene are subject to growth rate-dependent control, with at
      least one step being posttranscriptional. With both Northern (RNA) and slot blot
      analyses, we found that the amount of gnd mRNA relative to that of total RNA was
      2.5-fold higher in cells growing in glucose minimal medium than in cells grown on
      acetate. Therefore, since the total mRNA fraction of total RNA is essentially
      independent of the growth rate, the amount of gnd mRNA relative to that of total
      mRNA increases about 2.5-fold with increasing growth rate. This indicates that
      most of the growth rate-dependent increase in 6-phosphogluconate dehydrogenase
      can be accounted for by the growth rate-dependent increase in gnd mRNA level. We
      measured the decay of gnd mRNA mass in the two growth conditions after blocking
      transcription initiation with rifampin and found that the stability of gnd mRNA
      does not change with growth rate. We also used a gnd-lacZ protein fusion to
      measure the functional mRNA half-life and found that it too is growth rate
      independent. Thus, the growth rate-dependent increase in the level of gnd mRNA is
      due to an increase in gnd transcription, and this increase is sufficient to
      account for the growth rate regulation of the 6-phosphogluconate dehydrogenase
      level. The dilemma posed by interpretations of the properties of gnd-lac fusion
      strains and by direct measurement of gnd mRNA level is discussed.

PMID- 8282687
TI  - In vivo selection of conditional-lethal mutations in the gene encoding elongation
      factor G of Escherichia coli.
AB  - The ribosome translocation step that occurs during protein synthesis is a highly
      conserved, essential activity of all cells. The precise movement of one codon
      that occurs following peptide bond formation is regulated by elongation factor G
      (EF-G) in eubacteria or elongation factor 2 (EF-2) in eukaryotes. To begin to
      understand molecular interactions that regulate this process, a genetic selection
      was developed with the aim of obtaining conditional-lethal alleles of the gene
      (fusA) that encodes EF-G in Escherichia coli. The genetic selection depends on
      the observation that resistant strains arose spontaneously in the presence of
      sublethal concentrations of the antibiotic kanamycin. Replica plating was
      performed to obtain mutant isolates from this collection that were restrictive
      for growth at 42 degrees C. Two tightly temperature-sensitive strains were
      characterized in detail and shown to harbor single-site missense mutations within
      fusA. The fusA100 mutant encoded a glycine-to-aspartic acid change at codon 502.
      The fusA101 allele encoded a glutamine-to-proline alteration at position 495.
      Induction kinetics of beta-galactosidase activity suggested that both mutations
      resulted in slower elongation rates in vivo. These missense mutations were very
      near a small group of conserved amino acid residues (positions 483 to 493) that
      occur in EF-G and EF-2 but not EF-Tu. It is concluded that these sequences encode
      a specific domain that is essential for efficient translocase function.

PMID- 8282688
TI  - Mutations in ftsZ that confer resistance to SulA affect the interaction of FtsZ
      with GTP.
AB  - Mutations in the essential cell division gene ftsZ confer resistance to SulA, a
      cell division inhibitor that is induced as part of the SOS response. In this
      study we have purified and characterized the gene products of six of these mutant
      ftsZ alleles, ftsZ1, ftsZ2, ftsZ3, ftsZ9, ftsZ100, and ftsZ114, and compared
      their properties to those of the wild-type gene product. The binding of GTP was
      differentially affected by these mutations. FtsZ3 exhibited no detectable GTP
      binding, and FtsZ9 and FtsZ100 exhibited markedly reduced GTP binding. In
      contrast, FtsZ1 and FtsZ2 bound GTP almost as well as the wild type, and FtsZ114
      displayed increased GTP binding. Furthermore, we observed that all mutant FtsZ
      proteins exhibited markedly reduced intrinsic GTPase activity. It is likely that
      mutations in ftsZ that confer sulA resistance alter the conformation of the
      protein such that it assumes the active form.

PMID- 8282689
TI  - Isolation of suppressors of temperature-sensitive folding mutations.
AB  - Mutations in the tailspike gene (gene 9) of Salmonella typhimurium phage P22 have
      been used to identify amino acid interactions during the folding of a polypeptide
      chain. Since temperature-sensitive folding (tsf) mutations cause folding defects
      in the P22 tailspike polypeptide chain, it is likely that mutants derived from
      these and correcting the original tsf defects (second-site intragenic
      suppressors) identify interactions during the folding pathway. We report the
      isolation and identification of second-site revertants to tsf mutants.

PMID- 8282690
TI  - Repressor mutations in the marRAB operon that activate oxidative stress genes and
      multiple antibiotic resistance in Escherichia coli.
AB  - Resistance to multiple antibiotics and certain oxidative stress compounds was
      conferred by three independently selected mutations (marR1, soxQ1, and cfxB1)
      that mapped to 34 min on the Escherichia coli chromosome. Mutations at this locus
      can activate the marRAB operon, in which marR encodes a putative repressor of mar
      transcription and marA encodes a putative transcriptional activator of defense
      genes against antibiotics and oxidants. Overexpression of the wild-type MarR
      protein reversed the phenotypes (antibiotic resistance and increased antioxidant
      enzyme synthesis) of all three mutants. DNA sequence analysis showed that, like
      marR1, the other two mutations were alterations of marR: a 285-bp deletion in
      cfxB1 and a GC-->AT transition at codon 70 (Ala-->Thr) in soxQ1. All three
      mutations cause increased amounts of mar-specific RNA, which supports the
      hypothesis that MarR has a repressor function in the expression of the marRAB
      operon. The level of mar RNA was further induced by tetracycline in both the
      marR1 and soxQ1 strains but not in the cfxB1 deletion mutant. In the cfxB1
      strain, the level of expression of a truncated RNA, with or without tetracycline
      exposure, was the same as the fully induced level in the other two mutants.
      Overproduction of MarR in the cfxB1 strain repressed the transcription of the
      truncated RNA and restored transcriptional inducibility by tetracycline. Thus,
      induction of the marRAB operon results from the relief of the repression exerted
      by MarR. The marRAB operon evidently activates both antibiotic resistance and
      oxidative stress genes.

PMID- 8282691
TI  - Purification and characterization of Clostridium perfringens 120-kilodalton
      collagenase and nucleotide sequence of the corresponding gene.
AB  - Clostridium perfringens type C NCIB 10662 produced various gelatinolytic enzymes
      with molecular masses ranging from approximately 120 to approximately 80 kDa. A
      120-kDa gelatinolytic enzyme was present in the largest quantity in the culture
      supernatant, and this enzyme was purified to homogeneity on the basis of sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme was
      identified as the major collagenase of the organism, and it cleaved typical
      collagenase substrates such as azocoll, a synthetic substrate (4
      phenylazobenzyloxy-carbonyl-Pro-Leu-Gly-Pro-D-Arg [Pz peptide]), and a type I
      collagen fibril. In addition, a gene (colA) encoding a 120-kDa collagenase was
      cloned in Escherichia coli. Nested deletions were used to define the coding
      region of colA, and this region was sequenced; from the nucleotide sequence, this
      gene encodes a protein of 1,104 amino acids (M(r), 125,966). Furthermore, from
      the N-terminal amino acid sequence of the purified enzyme which was found in this
      reading frame, the molecular mass of the mature enzyme was calculated to be
      116,339 Da. Analysis of the primary structure of the gene product showed that the
      enzyme was produced with a stretch of 86 amino acids containing a putative signal
      sequence. Within this stretch was found PLGP, the amino acid sequence
      constituting the Pz peptide. This sequence may be implicated in self-processing
      of the collagenase. A consensus zinc-binding sequence (HEXXH) suggested for
      vertebrate Zn collagenases is present in this bacterial collagenase. Vibrio
      alginolyticus collagenase and Achromobacter lyticus protease I showed significant
      homology with the 120-kDa collagenase of C. perfringens, suggesting that these
      three enzymes are evolutionarily related.

PMID- 8282692
TI  - The pho regulon-dependent Ugp uptake system for glycerol-3-phosphate in
      Escherichia coli is trans inhibited by Pi.
AB  - sn-Glycerol-3-phosphate (G3P) or glyceryl phosphoryl phosphodiesters, the
      substrates of the phoB-dependent Ugp transport system, when transported
      exclusively through this system, can serve as a sole source of phosphate but not
      as a sole source of carbon (H. Schweizer, M. Argast, and W. Boos, J. Bacteriol.
      150:1154-1163, 1982). In order to explain this phenomenon, we tested two
      possibilities: repression of the pho regulon by Ugp-mediated transport and
      feedback inhibition by internal G3P or its degradation product Pi. Using an ugp
      lacZ fusion, we found that the expression of ugp does not decline upon exposure
      to G3P, in contrast to the repressing effect of transport of Pi via the Pst
      system. This indicated that the Ugp system becomes inhibited after the uptake and
      metabolism of G3P. Using 32P-labeled G3P, we observed that little Pi is released
      by cells taking up G3P via the Ugp system but large amounts of Pi are released
      when the cells are taking up G3P via the GlpT system. Using a glpD mutant that
      could not oxidize G3P but which could still phosphorylate exogenous glycerol to
      G3P after GlpF-mediated transport of glycerol, we could not find trans inhibition
      of Ugp-mediated uptake of exogenous 14C-G3P. However, when allowing uptake of Pi
      via Pst, we observed a time-dependent inhibition of 14C-G3P taken up by the Ugp
      transport system. Inhibition was half maximal after 2 min and could be elicited
      by Pi concentrations below 0.5 mM. Cells had to be starved for Pi in order to
      observe this inhibition. We conclude that the activity of the Ugp transport
      system is controlled by the level of internal phosphate.

PMID- 8282693
TI  - Cloning and nucleotide sequence of the cyclic AMP receptor protein-regulated
      Salmonella typhimurium pepE gene and crystallization of its product, an alpha
      aspartyl dipeptidase.
AB  - The Salmonella typhimurium pepE gene, encoding an N-terminal-Asp-specific
      dipeptidase, has been cloned on pBR328 by complementation of the Asp-Pro growth
      defect conferred by a pepE mutation. Strains carrying the complementing plasmids
      greatly overproduce peptidase E. The enzyme has been purified from an extract of
      such a strain, its N-terminal amino acid sequence has been determined, and
      crystals suitable for X-ray diffraction have been grown. A new assay using L
      aspartic acid p-nitroanilide as a substrate has been used to determine the pH
      optimum (approximately 7.5) and to test the effect of potential inhibitors.
      Insertions of transposon gamma delta (Tn1000) into one of the plasmids have been
      used to localize the gene and as sites for priming sequencing reactions. The
      nucleotide sequence of a 1,088-bp region of one of these plasmids has been
      determined. This sequence contains an open reading frame that predicts a 24.8-kDa
      protein with an N-terminal sequence that agrees with that determined for
      peptidase E. The predicted peptidase E amino acid sequence is not similar to that
      of any other known protein. The nucleotide sequence of the region upstream from
      pepE contains a promoter with a cyclic AMP receptor protein (CRP) site, and the
      effects of growth medium and of a crp mutation on expression of a pepE-lacZ
      fusion indicate that pepE is a member of the CRP regulon. The unique specificity
      of peptidase E and its lack of sequence similarity to any other peptidase suggest
      that this enzyme may be the prototype of a new class of peptidases. Its
      regulation by CPR and its specificity suggest that the enzyme may play a role in
      allowing the cell to use peptide aspartate to spare carbon otherwise required for
      the synthesis of the aspartate family of amino acids.

PMID- 8282694
TI  - Molecular cloning, chromosomal mapping, and sequence analysis of copper
      resistance genes from Xanthomonas campestris pv. juglandis: homology with small
      blue copper proteins and multicopper oxidase.
AB  - Copper-resistant strains of Xanthomonas campestris pv. juglandis occur in walnut
      orchards throughout northern California. The copper resistance genes from a
      copper-resistant strain C5 of X. campestris pv. juglandis were cloned and located
      on a 4.9-kb ClaI fragment, which hybridized only to DNA of copper-resistant
      strains of X. campestris pv. juglandis, and was part of an approximately 20-kb
      region which was conserved among such strains of X. campestris pv. juglandis.
      Hybridization analysis indicated that the copper resistance genes were located on
      the chromosome. Plasmids conferring copper resistance were not detected in copper
      resistant strains, nor did mating with copper-sensitive strains result in copper
      resistant transconjugants. Copper resistance genes from X. campestris pv.
      juglandis shared nucleotide sequence similarity with copper resistance genes from
      Pseudomonas syringae pv. tomato, P. syringae, and X. campestris pv. vesicatoria.
      DNA sequence analysis of the 4.9-kb fragment from strain C5 revealed that the
      sequence had an overall G+C content of 58.7%, and four open reading frames (ORF1
      to ORF4), oriented in the same direction. All four ORFs were required for full
      expression of copper resistance, on the basis of Tn3-spice insertional
      inactivation and deletion analysis. The predicted amino acid sequences of ORF1 to
      ORF4 showed 65, 45, 47, and 40% identity with CopA, CopB, CopC, and CopD,
      respectively, from P. syringae pv. tomato. The most conserved regions are ORF1
      and CopA and the C-terminal region (166 amino acids from the C terminus) of ORF2
      and CopB. The hydrophobicity profiles of each pair of predicted polypeptides are
      similar except for the N terminus of ORF2 and CopB. Four histidine-rich
      polypeptide regions in ORF1 and CopA strongly resembled the copper-binding motifs
      of small blue copper proteins and multicopper oxidases, such as fungal laccases,
      plant ascorbate oxidase, and human ceruloplasmin. Putative copper ligands of the
      ORF1 polypeptide product are proposed, indicating that the polypeptide of ORF1
      might bind four copper ions: one type 1, one type 2, and two type 3.

PMID- 8282695
TI  - Molecular characterization, nucleotide sequence, and expression of the fliO,
      fliP, fliQ, and fliR genes of Escherichia coli.
AB  - The fliL operon of Escherichia coli contains seven genes that are involved in the
      biosynthesis and functioning of the flagellar organelle. DNA sequences for the
      first three genes of this operon have been reported previously. A 2.2-kb PstI
      restriction fragment was shown to complement known mutant alleles of the fliO,
      fliP, fliQ, and fliR genes, the four remaining genes of the fliL operon. Four
      open reading frames were identified by DNA sequence analysis and correlated to
      their corresponding genes by complementation analysis. These genes were found to
      encode very hydrophobic polypeptides with molecular masses of 11.1, 26.9, 9.6,
      and 28.5 kDa for FliO, FliP, FliQ, and FliR, respectively. Analysis of
      recombinant plasmids in a T7 promoter-polymerase expression system enabled us to
      identify three of the four gene products. On the basis of DNA sequence analysis
      and in vivo protein expression, it appears that the fliP gene product is
      synthesized as a precursor protein with an N-terminal signal peptide of 21 amino
      acids. The FliP protein was homologous to proteins encoded by a DNA sequence
      upstream of the flaA gene of Rhizobium meliloti, to a gene involved in
      pathogenicity in Xanthomonas campestris pv. glycines, and to the spa24 gene of
      the Shigella flexneri. The latter two genes encode proteins that appear to be
      involved in protein translocation, suggesting that the FliP protein may have a
      similar function.

PMID- 8282696
TI  - Translation initiation factor IF1 is essential for cell viability in Escherichia
      coli.
AB  - Translation initiation factor IF1 is a highly conserved element of the
      prokaryotic translational apparatus. It has been demonstrated earlier that the
      factor stimulates in vitro the initiation phase of protein synthesis. However, no
      mutation in its gene, infA, has been identified, and a role for IF1 in
      translation has not been demonstrated in vivo. To elucidate the function of IF1
      and determine if the protein is essential for cell growth, the chromosomal copy
      of infA was disrupted. Cell viability is maintained only when infA is expressed
      in trans from a plasmid, thereby demonstrating that IF1 is essential for cell
      growth in Escherichia coli. Cells depleted of IF1 exhibit few polysomes,
      suggesting that IF1 functions in the initiation phase of protein synthesis.

PMID- 8282697
TI  - The chemokinetic and chemotactic behavior of Rhodobacter sphaeroides: two
      independent responses.
AB  - Rhodobacter sphaeroides exhibits two behavioral responses when exposed to some
      compounds: (i) a chemotactic response that results in accumulation and (ii) a
      sustained increase in swimming speed. This latter chemokinetic response occurs
      without any apparent long-term change in the size of the electrochemical proton
      gradient. The results presented here show that the chemokinetic response is
      separate from the chemotactic response, although some compounds can induce both
      responses. Compounds that caused only chemokinesis induced a sustained increase
      in the rate of flagellar rotation, but chemoeffectors which were also chemotactic
      caused an additional short-term change in both the stopping frequency and the
      duration of stops and runs. The response to a change in chemoattractant
      concentration was a transient increase in the stopping frequency when the
      concentration was reduced, with adaptation taking between 10 and 60 s. There was
      also a decrease in the stopping frequency when the concentration was increased,
      but adaptation took up to 60 min. The nature and duration of both the chemotactic
      and chemokinetic responses were concentration dependent. Weak organic acids
      elicited the strongest chemokinetic responses, and although many also caused
      chemotaxis, there were conditions under which chemokinesis occurred in the
      absence of chemotaxis. The transportable succinate analog malonate caused
      chemokinesis but not chemotaxis, as did acetate when added to a mutant able to
      transport but not grow on acetate. Chemokinesis also occurred after incubation
      with arsenate, conditions under which chemotaxis was lost, indicating that
      phosphorylation at some level may have a role in chemotaxis. Aspartate was the
      only chemoattractant amino acid to cause chemokinesis. Glutamate caused
      chemotaxis but not chemokinesis. These data suggest that (i) chemotaxis and
      chemokinesis are separate responses, (ii) metabolism is required for chemotaxis
      but not chemokinesis, (iii) a reduction in chemoattractant concentration may
      cause the major chemotactic signal, and (iv) a specific transport pathway(s) may
      be involved in chemokinetic signalling in R. sphaeroides.

PMID- 8282698
TI  - Analysis of Borrelia burgdorferi membrane architecture by freeze-fracture
      electron microscopy.
AB  - Freeze-fracture electron microscopy was used to investigate the membrane
      architectures of high-passage Borrelia burgdorferi B31 and low- and high-passage
      isolates of B. burgdorferi N40. In all three organisms, fractures occurred almost
      exclusively through the outer membrane (OM), and the large majority of
      intramembranous particles were distributed randomly throughout the concave OM
      leaflet. The density of intramembranous particles in the concave OM leaflet of
      the high-passage N40 isolate was significantly greater than that in the
      corresponding leaflet of the low-passage N40 isolate. Also noted in the OMs of
      all three organisms were unusual structures, designated linear bodies, which
      typically were more or less perpendicular to the axis of the bacterium. A
      comparison of freeze-fractured B. burgdorferi and Treponema pallidum, the
      syphilis spirochete, revealed that the OM architectures of these two pathogens
      differed markedly. All large membrane blebs appeared to be bounded by a membrane
      identical to the OM of B. burgdorferi whole cells; in some blebs, the fracture
      plane also revealed a second bilayer closely resembling the B. burgdorferi
      cytoplasmic membrane. Aggregation of the lipoprotein immunogens outer surface
      protein A (OspA) and OspB on the bacterial surface by incubation of B.
      burgdorferi B31 with specific polyclonal antisera did not affect the distribution
      of OM particles, supporting the contention that lipoproteins do not form
      particles in freeze-fractured OMs. The expression of poorly immunogenic, surface
      exposed proteins as virulence determinants may be part of the parasitic strategy
      used by B. burgdorferi to establish and maintain chronic infection in Lyme
      disease.

PMID- 8282699
TI  - Characterization of the Vibrio anguillarum fur gene: role in regulation of
      expression of the FatA outer membrane protein and catechols.
AB  - The chromosomally encoded Vibrio anguillarum fur gene was characterized. The
      amino acid sequence of the Fur protein showed a very high degree of homology with
      those of V. cholerae and V. vulnificus. The degree of homology was lower,
      although still high, with the Escherichia coli and Yersinia pestis Fur amino acid
      sequences, while the lowest degree of homology was found with the Pseudomonas
      aeruginosa Fur protein. The C-terminal portion of Fur is the least conserved
      region among these Fur proteins. Within this portion, two regions spanning amino
      acids 105 to 121 and 132 to the end are the least conserved. A certain degree of
      variation is also present in the N termini spanning amino acids 28 to 46.
      Regulation of expression of the V. anguillarum fur gene by iron was not detected
      by immunoblot analysis. Mutations in the cloned fur gene were generated either by
      site-directed mutagenesis (the Lys-77 was changed to a Gly to generate the
      derivative FurG77) or by insertion of a DNA fragment harboring the aph gene in
      the same position. FurG77 was impaired in its ability to regulate a reporter gene
      with the Fur box in its promoter, while the insertion mutant was completely
      inactive. V. anguillarum fur mutants were obtained by isolating manganese
      resistant derivatives. In one of these mutants, which encoded a Fur protein with
      an apparent lower molecular weight, the regulation of the production of catechols
      and synthesis of the outer membrane protein FatA were partially lost. In the case
      of another mutant, no protein was detected by anti-Fur serum. This derivative
      showed a total lack of regulation of biosynthesis of catechols and FatA protein
      by iron.

PMID- 8282700
TI  - Organization and functions of genes in the upstream region of tyrT of Escherichia
      coli: phenotypes of mutants with partial deletion of a new gene (tgs).
AB  - A delta tyrT::kan mutant from Escherichia coli K-12 (DTK-12) shows a transient
      growth lag that is caused by glycine starvation (U. Michelsen, M. Bosl, T.
      Dingermann, and H. Kersten, J. Bacteriol. 171:5987-5994, 1989). The same
      deletion, transduced into the relA1 spoT1 mutant CA274 to construct strain
      DTC274, caused complete growth inhibition in glucose minimal medium. Here, we
      show that the tyrT 5' region contains three new open reading frames in the order
      ORF37-->ORF34-->ORF32-->tyrT and that the delta tyrT::kan allele used previously
      deletes tyrT as well as a carboxy-terminal portion of ORF32. A plasmid encoding
      ORF32 totally complemented the inability of strain DTC274 to grow on glucose
      minimal medium as well as the transient glycine starvation phenomenon in DTK-12,
      and ORF32 was designated tgs. Partial deletion of tgs, cotransduced with the
      marker delta tyrT::kan, was responsible for the completely different phenotypes
      of the deletion mutants DTK-12 and DTC274. The deduced Tgs protein sequence
      showed significant homology to the PurN protein of E. coli and to enzymes with
      glycinamide ribonucleotide transformylase activity. We discuss whether growth
      inhibition in strain DTC274 may be caused by synergistic effects with the
      preexisting mutations relA1 and spoT1. The deduced protein sequence of ORF37
      showed striking similarity to regulator response proteins and is probably a new
      member of this family. A spontaneous mutation in ORF37, caused by the integration
      of an insertion element, IS1, exhibited no phenotype.

PMID- 8282701
TI  - Coexpression of eukaryotic tRNASer and yeast seryl-tRNA synthetase leads to
      functional amber suppression in Escherichia coli.
AB  - In order to gain insight into the conservation of determinants for tRNA identity
      between organisms, Schizosaccharomyces pombe and human amber suppressor serine
      tRNA genes have been examined for functional expression in Escherichia coli. The
      primary transcripts, which originated from E. coli plasmid promoters, were
      processed into mature tRNAs, but they were poorly aminoacylated in E. coli and
      thus were nonfunctional as suppressors in vivo. However, coexpression of cloned
      Saccharomyces cerevisiae seryl-tRNA synthetase led to efficient suppression in E.
      coli. This shows that some, but not all, determinants specifying the tRNASer
      identity are conserved in evolution.

PMID- 8282702
TI  - Analysis of the complexity of gene regulation by fur in Vibrio cholerae.
AB  - Iron concentration influences the expression of a number of genes involved in
      iron uptake and virulence in bacteria. In Escherichia coli, coordinate regulation
      of these genes by iron depends on the product of the fur gene, which acts as an
      iron-responsive, DNA-binding repressor protein. Several genes in Vibrio cholerae
      are also repressed by iron; and a fur gene, homologous to E. coli fur, has been
      previously cloned from this organism. The present study was undertaken to define
      the roles of Fur and iron in regulating gene expression in V. cholerae. V.
      cholerae strains with a mutation in fur by virtue of suicide plasmid integration
      into this gene showed derepressed expression of two previously characterized,
      iron-regulated genes, irgA and viuA, in high concentrations of iron; even in the
      fur mutants, however, residual two- to threefold regulation by iron persisted.
      The fur mutant strains constructed by suicide plasmid integration required
      antibiotic selection to maintain the mutation. To analyze further the effect of
      Fur and iron on gene regulation in V. cholerae without the need for antibiotic
      selection, we used in vivo marker exchange to construct a nonrevertible V.
      cholerae fur mutant. This V. cholerae fur mutant grew significantly less well in
      Luria-Bertani medium than the wild-type parent but grew slightly better than the
      wild type under iron-restricted conditions. The V. cholerae fur mutant was unable
      to utilize a number of carbon sources including glycerol, acetate, succinate,
      lactate, and fumarate, that supported growth of the wild-type strain on minimal
      media. We utilized two-dimensional gel electrophoresis of whole-cell protein
      extracts from the fur mutant and wild-type strains following growth in conditions
      of either low or high concentrations of iron to identify proteins regulated by
      iron and/or Fur. Twenty-two proteins were negatively regulated by iron in the
      wild-type strain but constitutively expressed in the fur mutant, consistent with
      the model of Fur as an iron-dependent repressor. However, many other proteins
      were regulated in a different manner by iron and/or Fur. Seventeen proteins were
      negatively regulated by iron but independent of Fur, suggesting the presence of
      an additional iron-dependent repressor(s). Six proteins were strongly iron
      regulated in the fur mutant but hardly expressed at all in the wild-type strain
      regardless of the iron concentration, suggesting an interaction between Fur and
      another iron regulatory mechanism. There were 11 proteins that were induced
      rather than repressed by iron, in four different regulatory classes. Gene
      regulation in V. cholerae by Fur and iron is much more complex than previously
      thought and is reminiscent of the Lrp regulon in E.coli.

PMID- 8282703
TI  - TRK2 is not a low-affinity potassium transporter in Saccharomyces cerevisiae.
AB  - TRK1 and TRK2 encode proteins involved in K+ uptake in Saccharomyces cerevisiae.
      A kinetic study of Rb+ influx in trk1 TRK2, trk1 TRK2D, and trk1 trk2 mutants
      reveals that TRK2 shows moderate affinity for Rb+. K(+)-starved trk1 delta TRK2
      cells show a low-affinity component accounting for almost the total Vmax of the
      influx and a moderate-affinity component exhibiting a very low Vmax.
      Overexpression of TRK2 in trk1 delta TRK2D cells increases the Vmax of the
      moderate-affinity component, and this component disappears in trk1 delta trk2
      delta cells. In contrast, the low-affinity component of Rb+ influx in trk1 delta
      TRK2 cells is not affected by mutations in TRK2. Consistent with the different
      levels of activity of the moderate-affinity Rb+ influx, trk1 delta TRK2 cells
      grow slowly in micromolar K+, trk1 delta TRK2D cells grow rapidly, and trk1 delta
      trk2 delta cells fail to grow. The existence of a unique K+ uptake system
      composed of several proteins is also discussed.

PMID- 8282704
TI  - Differential in vitro methylation and synthesis of the 480-kilodalton corrinoid
      protein in Methanosarcina barkeri grown on different substrates.
AB  - The 480-kDa corrinoid protein was significantly methylated in extracts of acetate
      but not methanol-grown cells incubated with 14CH3OH, in part because of its
      decreased synthesis in cells grown on substrates other than acetate. In addition,
      a 200-kDa corrinoid protein was methylated in extracts of methanol- but not
      acetate-grown cells.

PMID- 8282705
TI  - Artifactual processing of penicillin-binding proteins 7 and 1b by the OmpT
      protease of Escherichia coli.
AB  - Penicillin-binding proteins (PBPs) were visualized in strains of Escherichia coli
      that carried mutations in one or more of the following protease genes: tsp, degP,
      ptr, and ompT. In the absence of a functional ompT gene, PBPs 1b alpha and 7 were
      not processed to the shortened forms 1b beta and 8, respectively. Cleavage of
      PBPs 1b alpha and 7 could be restored by introduction of a plasmid carrying the
      wild-type ompT gene. These PBPs were processed only after cell lysis or after
      membrane perturbation of whole cells by freeze-thaw, suggesting that the cleavage
      was a nonspecific artifact due to contact with OmpT, an outer membrane protease,
      and that such processing was not biologically significant in vivo. The
      degradation of other PBPs during purification or storage may also be effected by
      OmpT.

PMID- 8282706
TI  - Vancomycin-resistant Leuconostoc mesenteroides and Lactobacillus casei synthesize
      cytoplasmic peptidoglycan precursors that terminate in lactate.
AB  - The emergence of acquired high-level resistance among Enterococcus species has
      renewed interest in mechanisms of resistance to glycopeptide antibiotics in gram
      positive bacteria. In Enterococcus faecalis and Enterococcus faecium, resistance
      is encoded by the van gene cluster and is due to the production of a
      peptidoglycan precursor terminating in D-alanyl-D-lactate, to which vancomycin
      does not bind. Most Leuconostoc and many Lactobacillus species are intrinsically
      resistant to high levels of glycopeptide antibiotics, but the mechanism of
      resistance has not been elucidated. To determine whether the mechanisms of
      resistance are similar in intrinsically resistant bacteria, cytoplasmic
      peptidoglycan precursors were isolated from Leuconostoc mesenteroides and
      Lactobacillus casei and analyzed by mass spectrometry, revealing structures
      consistent with UDP-N-acetylmuramyl-L-Ala-D-Glu-L-Lys-(L-Ala)-D-Ala-D-lactate and
      UDP-N-acetylmuramyl-L-Ala-D-Glu-L-Lys-D-Ala-D-lactate, respectively.

PMID- 8282707
TI  - Uninterrupted translation through putative 12-nucleotide coding gap in sequence
      of carA: business as usual.
AB  - Previous work of others reported an untranslated stretch of 12 nucleotides in the
      5' coding sequence of carA from Pseudomonas aeruginosa. However, N-terminal
      protein sequencing of carA-lacZ translational fusions shows that these 12
      nucleotides are normally translated in a continuous triplet manner, both in P.
      aeruginosa and in Escherichia coli.

PMID- 8282708
TI  - prrA, a putative response regulator involved in oxygen regulation of
      photosynthesis gene expression in Rhodobacter sphaeroides.
AB  - A new locus, prrA, involved in the regulation of photosynthesis gene expression
      in response to oxygen, has been identified in Rhodobacter sphaeroides.
      Inactivation of prrA results in the absence of photosynthetic spectral complexes.
      The prrA gene product has strong homology to response regulators associated with
      signal transduction in other prokaryotes. When prrA is present in multiple
      copies, cells produce light-harvesting complexes under aerobic growth conditions,
      suggesting that prrA affects photosynthesis gene expression positively in
      response to oxygen deprivation. Analysis of the expression of puc::lacZ fusions
      in wild-type and PrrA- cells revealed a substantial decrease in LacZ expression
      in the absence of prrA under all conditions of growth, especially when cells were
      grown anaerobically in the dark in the presence of dimethyl sulfoxide. Northern
      (RNA) and slot blot hybridizations confirmed the beta-galactoside results for puc
      and revealed additional positive regulation of puf, puhA, and cycA by PrrA. The
      effect of truncated PrrA on photosynthesis gene expression in the presence of low
      oxygen levels can be explained by assuming that PrrA may be effective as a
      multimer. PrrA was found to act on the downstream regulatory sequences (J. K. Lee
      and S. Kaplan, J. Bacteriol. 174:1146-1157, 1992) of the puc operon regulatory
      region. Finally, two spontaneous prrA mutations that abolish prrA function by
      changing amino acids in the amino-terminal domain of the protein were isolated.

PMID- 8282709
TI  - GTPase-dependent signaling in bacteria: characterization of a membrane-binding
      site for era in Escherichia coli.
AB  - Era is an Escherichia coli GTPase that is essential for cell viability and is
      peripherally associated with the cytoplasmic membrane. Both immunoelectron
      microscopy and subcellular-fractionation experiments have shown that Era is
      present in cytoplasmic as well as membrane-associated pools. These data led to
      speculation that the mechanism of action of Era may require cycling between
      membrane and cytoplasmic sites. In order to investigate this possibility, an in
      vitro binding assay was developed to characterize the binding of Era to membrane
      fractions. Competition and saturation binding experiments suggest that a site
      that is specific for Era and capable of binding up to 5 ng of Era per microgram
      of membrane protein is present in membrane preparations. The binding curve is
      complex, indicating that multiple equilibria describe the interaction. The
      binding of Era to this putative receptor is dependent on guanine nucleotides;
      binding cannot be measured in the absence of nucleotide, and neither ATP nor UTP
      can substitute. Subfractionation of cell walls showed that the guanine nucleotide
      dependent binding site was present in fractions enriched in cytoplasmic membrane.
      These data provide evidence that Era may be involved in a GTPase-receptor-coupled
      membrane-signaling pathway that is essential for growth in E. coli.

PMID- 8282710
TI  - The Bacillus subtilis nucleoid-associated protein HPB12 strongly compacts DNA.
AB  - The HPB12 protein from the nucleoid of Bacillus subtilis was previously
      described, and its DNA binding properties have been reported previously (V.
      Salti, F. Le Hegarat, and L. Hirschbein, Biochim. Biophys. Acta 1009:161-167,
      1989). The DNA-HPB12 complexes were examined by electron microscopy. They
      appeared as short, slightly curved rods whereas naked DNA showed no compaction.
      Since only a small number of complexes with an intermediate degree of folding
      were observed, it appears that the nucleoid-associated protein HPB12 binds
      cooperatively to DNA, confirming Salti et al. (V. Salti, F. Le Hegarat, and L.
      Hirschbein, Biochim. Biophys. Acta 1009:161-167, 1989), and gives rise to a
      tightly compacted DNA-protein complex. N-terminal sequencing of purified HPB12
      showed that all but one of the first 26 amino acids were identical to those of
      the L24 ribosomal protein.

PMID- 8282711
TI  - Nucleotide sequence and characterization of the Rhodobacter capsulatus hvrB gene:
      HvrB is an activator of S-adenosyl-L-homocysteine hydrolase expression and is a
      member of the LysR family.
AB  - Here we present the nucleotide sequence and characterization of two genes, hvrB
      and orf5, that are located in the regulatory gene cluster from Rhodobacter
      capsulatus. The hvrB gene, which encodes a protein with a predicted molecular
      mass of 32 kDa, is shown to be highly homologous to genes encoding members of the
      LysR family of bacterial transcriptional regulators. A chromosomal disruption of
      hvrB is shown to result in the failure to regulate expression from the nearby
      ahcY and orf5 genes in response to alterations in light intensity. We show by
      primer extension mapping that the 5' end of ahcY-specific mRNA defines a promoter
      region exhibiting sequence similarity to known R. capsulatus promoter elements.
      Our mutational analysis further demonstrates that hvrB autoregulates its own
      expression in vivo.

PMID- 8282712
TI  - Responses to nutrient starvation in Pseudomonas putida KT2442: analysis of
      general cross-protection, cell shape, and macromolecular content.
AB  - The physiology of Pseudomonas putida KT2442 with respect to growth and carbon
      starvation was studied. During the transition from growth to nongrowth, the cell
      shape changes from cylindrical to spheric, a change which is accompanied by
      reductions in cell size, DNA and ribosome content, and the rate of total protein
      synthesis. In addition, a pattern of general cross-protection develops, which
      enables the cells to survive environmental stresses such as high and low
      temperatures, elevated osmolarity, solvents, and oxidative agents. Cultures are
      almost fully viable during 1 month of carbon, nitrogen, and multiple-nutrient
      starvation and are considered to be in an active nondormant state. In contrast,
      strain KT2442 does not survive well under conditions of sulfate and phosphate
      starvation.

PMID- 8282713
TI  - Multicomplex cellulase-xylanase system of Clostridium papyrosolvens C7.
AB  - The cellulase system of Clostridium papyrosolvens C7 was fractionated by means of
      ion-exchange chromatography into at least seven high-molecular-weight
      multiprotein complexes, each with different enzymatic and structural properties.
      The molecular weights of the complexes, as determined by gel filtration
      chromatography, ranged from 500,000 to 660,000, and the isoelectric points ranged
      from 4.40 to 4.85. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      analysis of the complexes showed that each complex had a distinct polypeptide
      composition. Avicelase, carboxymethyl cellulase, and xylanase activity profiles
      differed from protein complex to protein complex. Three of the complexes
      hydrolyzed crystalline cellulose (Avicel). Activity zymograms of gels (following
      electrophoresis under mildly denaturing conditions) revealed different
      carboxymethyl cellulase-active proteins in all complexes but xylanase-active
      proteins in only two of the complexes. The xylanase specific activity of these
      two complexes was more than eightfold higher than that of the unfractionated
      cellulase preparation. A 125,000-M(r) glycoprotein with no apparent enzyme
      activity was the only polypeptide present in all seven complexes. Experiments
      involving recombination of samples eluted from the ion-exchange chromatography
      column indicated that synergistic interactions occurred in the hydrolysis of
      crystalline cellulose by the cellulase system. We propose that the C.
      papyrosolvens enzyme system responsible for the hydrolysis of crystalline
      cellulose and xylan is a multicomplex system comprising at least seven diverse
      protein complexes.

PMID- 8282714
TI  - Exogenous myristic acid can be partially degraded prior to activation to form
      acyl-acyl carrier protein intermediates and lipid A in Vibrio harveyi.
AB  - To study the involvement of acyl carrier protein (ACP) in the metabolism of
      exogenous fatty acids in Vibrio harveyi, cultures were incubated in minimal
      medium with [9,10-3H]myristic acid, and labeled proteins were analyzed by gel
      electrophoresis. Labeled acyl-ACP was positively identified by
      immunoprecipitation with anti-V. harveyi ACP serum and comigration with acyl-ACP
      standards and [3H]beta-alanine-labeled bands on both sodium dodecyl sulfate- and
      urea-polyacrylamide gels. Surprisingly, most of the acyl-ACP label corresponded
      to fatty acid chain lengths of less than 14 carbons: C14, C12, C10, and C8
      represented 33, 40, 14, and 8% of total [3H]14:0-derived acyl-ACPs, respectively,
      in a dark mutant (M17) of V. harveyi which lacks myristoyl-ACP esterase activity;
      however, labeled 14:0-ACP was absent in the wild-type strain. 14:0- and 12:0-ACP
      were also the predominant species labeled in complex medium. In contrast, short
      chain acyl-ACPs (< or = C6) were the major labeled derivatives when V. harveyi
      was incubated with [3H]acetate, indicating that acyl-ACP labeling with [3H]14:0
      in vivo is not due to the total degradation of [3H]14:0 to [3H]acetyl coenzyme A
      followed by resynthesis. Cerulenin increased the mass of medium- to long-chain
      acyl-ACPs (> or = C8) labeled with [3H]beta-alanine fivefold, while total
      incorporation of [3H]14:0 was not affected, although a shift to shorter chain
      lengths was noted. Additional bands which comigrated with acyl-ACP on sodium
      dodecyl sulfate gels were identified as lipopolysaccharide by acid hydrolysis and
      thin-layer chromatography. The levels of incorporation of [3H] 14:0 into acyl-ACP
      and lipopolysaccharide were 2 and 15%, respectively, of that into phospholipid by
      10 min. Our results indicate that in contrast to the situation in Escherichia
      coli, exogenous fatty acids can be activated to acyl-ACP intermediates after
      partial degradation in V. harveyi and can effectively label products (i.e., lipid
      A) that require ACP as an acyl donor.

PMID- 8282715
TI  - The PII protein in the cyanobacterium Synechococcus sp. strain PCC 7942 is
      modified by serine phosphorylation and signals the cellular N-status.
AB  - The glnB gene product (PII protein) from Synechococcus sp. has previously been
      identified among 32P-labeled proteins, and its modification state has been
      observed to depend on both the nitrogen source and the spectral light quality (N.
      F. Tsinoremas, A. M. Castets, M. A. Harrison, J. F. Allen, and N. Tandeau de
      Marsac, Proc. Natl. Acad. Sci. USA 88:4565-4569, 1991). As shown in this study,
      modification of the PII protein primarily responds to the N-status of the cell,
      and its light-dependent variations are are mediated through nitrate metabolism.
      Modification of the PII protein results in the appearance of three isomeric forms
      with increasing negative charge. Unlike its homolog counterparts characterized so
      far, PII in Synechococcus sp. is modified by phosphorylation on a serine residue,
      which represents a unique kind of protein modification in bacterial nitrogen
      signalling pathways.

PMID- 8282716
TI  - In vitro motility of proteolytically cleaved myosin subfragment 1 on a lysine
      coated surface.
AB  - The in vitro motility of enzymatically cleaved S-1 was investigated with a novel
      procedure for the coating of a glass surface with poly-L-lysine. On a lysine
      coated surface, HMM and S-1 (mixture of 95 and 91 kDa fragments) moved F-actin
      filaments at average velocities of 4.41 and 1.54 microns/s, respectively, which
      are similar to those, 5.96 and 1.47 microns/s, on a collodion-coated surface,
      respectively. Myosin S-1 composed of the 91 kDa polypeptide could move F-actin at
      1.15 microns/s. Tryptically cleaved chymotryptic S-1 could move F-actin filaments
      at an average velocity of 2.8 microns/s: about 2 times that in the case of S-1.
      This activation of the sliding movement on cleaved S-1 arises partly from
      reduction of the drag force due to the low affinity of cleaved S-1 for F-actin.
      The motility of S-1 cleaved at other sites was also examined on a lysine-coated
      surface.

PMID- 8282717
TI  - Age dependency of mitochondrial DNA decrease differs in different tissues of rat.
AB  - Mitochondrial DNA contents were measured using non-radioactive DNA probes for
      specific mtDNA sequences. The nuclear repetitive DNA sequence, LINE, was used as
      an internal standard marker. Age-dependent decreases in the mtDNA/nucDNA ratio in
      rat hepatic cells were confirmed with this method and, furthermore, a similar
      decrease was found in cardiac muscles. On the other hand, in thigh skeletal
      muscles such a decrease was not observed, slight increases being rather found in
      18- to 24-month-old rats. The possible relationship of the decrease in mtDNA and
      the mechanism underlying animal senescence was discussed.

PMID- 8282718
TI  - Separation of large and small granules from horseshoe crab (Tachypleus
      tridentatus) hemocytes and characterization of their components.
AB  - We designed a method for separating two types of granules, a smaller (S) but
      dense and a larger (L) but less dense granule from hemocytes of the horseshoe
      crab (Tachypleus tridentatus), using continuous sucrose density gradient
      centrifugation. The isolated L-granules contained at least three clotting factors
      plus a clottable protein, coagulogen, as the major component. The known anti
      lipopolysaccharide factor and 7 additional unknown protein components were also
      present in the L-granules. Two known natural substrates, Pro-rich protein and 8.6
      kDa protein, for limulus transglutaminase [Tokunaga, F., Yamada, M., Miyata, T.,
      Ding, Y.-L., Hiranaga-Kawabata, M., Muta, T., Iwanaga, S., Ichinose, A., & Davie,
      E.W. (1993) J. Biol. Chem. 268, 252-261] were present in the L-granules. On the
      other hand, the isolated S-granules contained antimicrobial tachyplesins I and II
      (17 amino acids in length) as the major component, in addition to 6 unidentified
      proteins with molecular masses of less than 30 kDa. The structural analyses of
      tachyplesin analogs indicated that all these peptides of mature form are stored
      in the S-granules, together with a processing intermediate containing the COOH
      terminal Gly-Lys sequence. We also found an Arg-rich protein of 22 kDa and a Leu
      rich protein of 30 kDa in S-granules. Based on these observations, we speculate
      that protein components in L-granules, which probably contain all the factors
      essential for the limulus clotting system, participate in immobilization of
      invading microbes and that factors in the S-granules containing tachyplesins
      contribute to a self-defense system against invaders.

PMID- 8282719
TI  - Purification and characterization of endogenous protein activator of human
      platelet proteasome.
AB  - An endogenous activator of 20S proteasome was purified from human platelets and
      its effect on three peptidase activities of proteasome was studied. This
      activator had a molecular weight of 170 kDa, and was composed of 32 kDa
      polypeptides as determined by SDS-PAGE. It was highly labile upon heat treatment
      (56 degrees C, 20 s) and proteinase (pronase CB) digestion. Suc-LLVY-MCA
      degrading activity of the platelet proteasome showed positive cooperativity
      between two or more catalytic sites because the coefficient was 1.54 when
      analyzed by use of the Hill plot. The endogenous activator increased Vmax and
      caused a loss of cooperativity. The plot of reaction velocity as a function of
      activator concentration yielded a saturation curve, implying the binding of the
      activator to proteasome. Boc-LTR-MCA degrading activity followed Michaelis-Menten
      kinetics. The activator enhanced the activity by increasing Vmax and decreasing
      Km. In contrast, CBz-LLE-2NA degrading activity could not be analyzed according
      to any kinetic scheme reported so far. The activator stimulated this activity at
      lower substrate concentrations (below 200 microM), while it inhibited the
      activity at higher substrate concentrations (400-800 microM). It is concluded
      from these findings that the endogenous protein activator may regulate the
      intracellular proteasome activity by functioning as a positive allosteric
      effector.

PMID- 8282720
TI  - Effect of covalent binding of a derivative of 2',3'-O-(2,4,6-trinitrophenyl)-ADP
      to the tight binding site of CF1 on the enzyme activity.
AB  - Irradiation of isolated chloroplast thylakoids with TNP-ADP results in non
      covalent binding and covalent incorporation of a reaction product of TNP-ADP
      formed by photosynthetic reduction into the so-called "tight" nucleotide binding
      site of CF1 [Ponse et al. (1992) Z. Naturforsch. 47c, 264-274]. CF1 extracted
      from thus-loaded thylakoid membranes yielded maximal incorporation of 1 mol/mol
      of CF1. Almost half had the covalent bond with CF1. In experiments with TNP
      [14C]ADP, radioactivity was detected almost equivalently on alpha and beta
      subunits, suggesting that the binding site may be at the interface between alpha
      and beta subunits. Enzyme activities of the thylakoid membrane-bound enzyme after
      covalent labeling were measured. Inhibition, ranging from 20 to 25%, was less
      than expected from the percentage of CF1 molecules labeled (40-50%). It is
      suggested that only half of the labeled enzymes, probably those with the
      nucleotide analog linked to the beta subunit, are inactive.

PMID- 8282721
TI  - An ecto-enzyme from Sulfolobus acidocaldarius strain 7 which catalyzes hydrolysis
      of inorganic pyrophosphate, ATP, and ADP: purification and characterization.
AB  - Membranes of Sulfolobus acidocaldarius, a thermoacidophilic archaebacterium, show
      novel enzymatic activities to hydrolyze PPi, ATP, and ADP at an optimal pH of 3,
      equal to the growth optimum. The activity increased by about 2-fold on addition
      of PPi and/or Pi to the growth medium, when yeast extract and casamino acids were
      removed. The enzyme which hydrolyzes PPi at pH 3 was solubilized and purified by
      successive chromatographies. The final preparation showed a 26 kDa single band on
      SDS-PAGE, and a molecular mass of 35 kDa on gel permeation chromatography. The Km
      and Vmax for PPi were 0.16 mM and 33 mumol Pi released/min/mg at 55 degrees C.
      ATP and ADP were also good substrates. Divalent cations were not essential for
      activity. Substrate inhibition at more than 5 mM PPi, ATP or ADP was observed.
      AMP, glucose-6-phosphate, and p-nitrophenyl phosphate were not hydrolyzed at all.
      The activity was 4-fold stimulated by addition of the lipid fraction extracted
      from the organism.

PMID- 8282722
TI  - Structures of N-linked sugar chains expressed mainly in mouse brain.
AB  - Sugar chains were liberated from mouse tissues (liver, heart, spleen, kidney,
      thymus, cerebrum, cerebellum, and brain stem) by hydrazinolysis. After
      acetylation of the free amino groups, the sugar chains released were
      pyridylaminated. Pyridylamino (PA-) derivatives of the sugar chains from each
      tissue were fractionated by anion-exchange high-performance liquid chromatography
      (HPLC) according to their negative charges. Fractions containing PA-neutral sugar
      chains thus obtained were separated successively by size-fractionation HPLC and
      reversed-phase HPLC. Two sugar chains that were more abundant in neural tissues
      than in other tissues were purified. The structures of the two sugar chains were
      determined by sugar composition analysis, sequential exoglycosidase digestion,
      and methylation analysis. The proposed structures are shown below. A structure
      with n = 1 was found in the cerebrum, cerebellum, and brain stem. A structure
      with n = 0 was abundant in the cerebrum and brain stem, but less so in the
      cerebellum. [formula: see text]

PMID- 8282723
TI  - Immobilization of dihydrofolate reductase by engineered cysteine residue attached
      to its C-terminal end.
AB  - A cysteine residue with a short amino acid chain spacer was attached to the C
      terminal end of mutant dihydrofolate reductase [DHFR(C152E)] by a recombinant DNA
      technique. By using 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) as a SH reagent,
      it was determined that the reactivity of the SH group of the introduced C
      terminal cysteine was much higher than that of cysteines with the wild-type DHFR
      (C85 and C152), probably due to an increase of the solvent accessible surface
      area of the SH group. By utilizing the increased reactivity of the SH group of
      the C-terminal cysteine, the engineered DHFR was effectively immobilized to a
      thiopropyl-Sepharose gel. The amount of immobilized DHFR was estimated to be ca.
      6 mg/g of dried gel, and the activity of the bound DHFR was comparable to that of
      the free enzyme. Thus, the attachment of the cysteine residue to the C-terminal
      was extremely useful for immobilization of the enzyme.

PMID- 8282724
TI  - Mouse heparin binding protein-44 (HBP-44) associates with brushin, a high
      molecular-weight glycoprotein antigen common to the kidney and teratocarcinomas.
AB  - Heparin binding protein-44 (HBP-44) is a heparin binding protein of 44 kDa, found
      by cDNA cloning using antibodies against teratocarcinoma glycoproteins [Furukawa,
      T. et al. (1990) J. Biochem. 108, 297-302]. The N-terminal sequence analysis
      reported in this publication establishes the structure of its mature form.
      Immunohistochemical staining revealed that HBP-44 was located in the tubular
      brush border of the kidney. HBP-44 formed a complex with brushin, a high
      molecular weight (450 kDa) glycoprotein antigen common to the kidney and
      teratocarcinoma, but not with OR8 antigen, another antigen (350 kDa) of the same
      category. Brushin was shown to be the mouse counterpart of rat Heymann nephritis
      antigen, called gp330. The association between HBP-44 and brushin was revealed
      not only by co-precipitation upon indirect immunoprecipitation, but also by
      ligand blotting with HBP-44-maltose binding protein fusion protein. Calcium ion
      stabilized the association. Disulfide bonds in brushin seemed to be necessary for
      the complex formation, since reductive cleavage of the bonds resulted in failure
      of the protein to associate with HBP-44 in a ligand blotting experiment.
      Association of HBP-44 with brushin occurred both in teratocarcinoma cells, in
      which these molecules are mainly located in extraembryonic endoderm cells, and in
      the kidney, suggesting that the complex has an unknown common function in the
      renal tubular brush border and the extraembryonic endoderm.

PMID- 8282725
TI  - Novel members of the two-component signal transduction genes in Escherichia coli.
AB  - A variety of adaptive response systems in prokaryotes often involve two families
      (two components) of signal transduction proteins, namely, sensory kinases and
      response-regulators. To extend the list of such sensor/regulator genes for
      Escherichia coli, we adopted a random screening method in this study. In
      particular, we isolated a series of recombinant plasmids that are able
      phenotypically to suppress mutational lesions of both the envZ and phoR/creC
      genes, each of which encodes a well-characterized sensory-kinase. Among the
      recombinant plasmids thus isolated, two clones (named pSN11 and pSN25) were
      subjected to characterization in detail. These analyses allowed us to identify
      the genetic loci specifying novel members of the sensor/regulator families. One
      (pSN11) is located around 45 min on the E. coli genetic map, that contains two
      adjacent coding-sequences (baeS and baeR). The other (pSN25) is located around 93
      min of the genetic map, that also comprises two adjacent coding-sequences (basS
      and basR). These two pairs of gene-products, thus newly identified, were revealed
      to belong to typical members of the sensor/regulator families. Furthermore, they
      were demonstrated to exhibit the in vitro phosphotransfer reaction in the
      presence of ATP, that is also a characteristic of the sensory-kinase and response
      regulator proteins.

PMID- 8282726
TI  - Three polypeptides with distinct biochemical properties are major alpha chain
      size components of type IV collagen in bovine lens capsule.
AB  - Studies of intact type IV collagen from deposits of cultured cells or from
      tissues in culture, or more recently, isolated from EHS tumor have suggested that
      type IV collagen molecule is composed of two procollagen-like polypeptides (M(r)
      = 185k and 170k). We show that the major components of intact type IV collagen in
      bovine lens capsule are three polypeptides, two with sizes (M(r) = 180k and 175k)
      comparable to those of the procollagen-like polypeptides and one with a smaller
      size (M(r) = 160k). Both CNBr peptide mapping and electrophoretic analysis by
      utilizing a gel containing urea showed that the 180k polypeptide and the 160k
      polypeptide are chemically and genetically very similar to each other, but that
      the 175k polypeptide is chemically distinct from the other two polypeptides. It
      is unlikely that the 160k polypeptide resulted from cleavage of the 180k
      polypeptide during experimental manipulation, since a change of the acidic pH of
      extraction buffer to neutral pH, storage of the acid extract in acid for a
      prolonged time or incubation of the acid extract at 80 degrees C after
      neutralization gave rise to essentially no change in relative amount or size of
      the three polypeptides.

PMID- 8282727
TI  - Importance of successive prolines in the carboxy-terminal region of P450 2C2 and
      P450 2C14 for the hydroxylase activities.
AB  - Proline-480 and proline-481 are highly conserved in the P450 2 family. When these
      successive prolines of P450 2C2 were replaced by Ala-Thr, its activities of
      laurate (omega-1)-hydroxylation and benzphetamine N-demethylation were lost. On
      the other hand, the mutated P450 which retained one of the proline residues was
      60-100% active in the (omega-1)-hydroxylation and 100-120% active in the N
      demethylation. Pro-Pro (480, 481) to Ala-Thr mutated P450 2C14 was also inactive
      in testosterone 16 alpha-hydroxylation and benzphetamine N-demethylation, the
      activities of the wild-type P450 2C14. In the carboxyterminal region of the P450
      2C subfamily, the sequence of P450 2C2 from residues 469-473 is noticeably
      different from those of the other members of this subfamily. The Ser-473 to Val
      mutation of P450 2C2 caused a decrease in the (omega-1)-hydroxylase activity to
      one-fifth but the N-demethylase activity was not much affected. When the sequence
      of P450 2C2 from residues 469-473 was replaced by that of P450 2C14 (mutation at
      four residues), the 16 alpha-hydroxylase and N-demethylase activities were
      increased by seven- and three-fold, respectively, and the (omega-1)-hydroxylase
      activity was decreased to one-third. The mutated P450 2C2, in which the carboxy
      terminal four residue sequence or the proline cluster adjacent to the amino
      terminal membrane-anchor signal sequences was deleted, was not accumulated in
      yeast cells transformed with plasmids directing the synthesis of such
      P450s.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282728
TI  - 3-Isopropylmalate dehydrogenase from chemolithoautotroph Thiobacillus
      ferrooxidans: DNA sequence, enzyme purification, and characterization.
AB  - 3-Isopropylmalate dehydrogenase encoded by the Thiobacillus ferrooxidans leuB
      gene was purified to homogeneity from Escherichia coli cells harboring a
      recombinant plasmid containing the leuB gene. The native enzyme molecule is a
      dimer of molecular weight 38,000. The Km value for 3-isopropylmalate was
      estimated to be 26 microM and that for NAD+ 0.8 mM. The presence of K+ or NH4+ is
      essential for the enzyme reaction. The enzyme is activated about 4-fold by the
      addition of 1.0 mM Mg2+ or Co2+. The optimum pH and temperature for the activity
      are 9.0 and 60 degrees C, respectively. The properties of the enzyme are similar
      to those of the Salmonella typhimurium and Thermus thermophilus enzymes, except
      for substrate specificity. T. ferrooxidans 3-isopropylmalate dehydrogenase is
      able to utilize D- and L-malate as substrates in addition to 3-isopropylmalate.
      Sequencing of subcloned DNA revealed that the leuB gene consists of a 1,074 bp
      open reading frame and encodes 358 amino acid residues corresponding to the
      subunit (38,462 Da). The amino acid sequence of 3-isopropylmalate dehydrogenase
      from T. ferrooxidans and those of some heterotrophic microorganisms have high
      homology.

PMID- 8282729
TI  - Physiological and pathological changes in levels of the two small stress
      proteins, HSP27 and alpha B crystallin, in rat hindlimb muscles.
AB  - The two small stress proteins, HSP27 and alpha B crystallin, are expressed widely
      in normal rat tissues and abundantly in skeletal muscle. In order to clarify the
      physiological significance of these stress proteins, the changes in their levels
      were determined immunochemically, in the slow-twitch soleus muscle and fast
      twitch extensor digitorum longus muscle or rectus femoris muscle of growing rats,
      and in those of adult rats during denervation and tenotomy. HSP27 was quantitated
      by specific immunoassay, similar to that for alpha B crystallin, with antibodies
      raised in rabbits against purified rat HSP27. In adult rats, HSP27 was present at
      high levels in tissues composed of striated muscle, and it was present at much
      higher levels in the soleus muscle than in the rectus femoris or extensor
      digitorum longus muscle, as is alpha B crystallin. However, in rats of perinatal
      age (from prenatal day 2 to postnatal day 3), levels of HSP27 in the rectus
      femoris muscle were enhanced like those in the soleus muscle, reaching the
      maximum levels at postnatal day 3. Thereafter HSP27 in the fast-twitch muscle
      showed a steep decrease. The increase in alpha B crystallin in the hindlimb
      muscles was also observed in the perinatal period. However, alpha B crystallin
      concentrations in the soleus muscle of perinatal rats were as low as those in
      rectus femoris muscle. The transection of the sciatic nerve resulted in decreases
      in the levels of HSP27 and alpha B crystallin in the soleus muscle of adult rats,
      together with increases in the levels of the two proteins in the extensor
      digitorum longus muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282730
TI  - Signal transduction and sporulation in Bacillus subtilis: heterologous
      phosphorylation of Spo0A, a sporulation initiation gene product.
AB  - Spo0A is both a positive and a negative transcriptional regulator which plays a
      very important role in sporulation initiation in Bacillus subtilis. Its N
      terminal amino acid sequence is homologous to that of regulator proteins of the
      two-component regulatory systems involved in signal transduction in bacteria.
      Phosphorylation of Spo0A through phosphorelay has been reported by Burbulys et
      al. (1991). In this study, we found that (i) Spo0A is phosphorylated effectively
      with phospho-EnvZ* (N-terminal truncated EnvZ), which is a heterologous osmotic
      sensor protein in Escherichia coli, and (ii) a phosphorylation deficient mutant
      of Spo0A protein is completely defective in initiating sporulation. These results
      suggest that Spo0A phosphorylation may be an essential event in signal
      transduction of sporulation in B. subtilis and the signal transduction mechanism
      has a common feature in Gram-positive and Gram-negative bacteria.

PMID- 8282731
TI  - Potassium-stimulating mechanism of geranylgeranyl diphosphate synthase of
      Methanobacterium thermoformicicum SF-4.
AB  - The catalytic properties of geranylgeranyl diphosphate (GGPP) synthase [EC
      2.5.1.29] purified from Methanobacterium thermoformicicum SF-4 were studied by
      kinetic procedures. The plots of 1/v versus 1/[S] and inhibition patterns by
      enzyme reaction products, PPi and GGPP, showed that the GGPP synthase reaction
      mechanism is an ordered-sequential Bi Bi one. Monovalent cations at low
      concentration (0.05 M) enhanced the enzyme activity, but at high concentration
      (0.4 M) they were inhibitory, except for K+. The K+ ion was found to be a
      modifier forming a parallel reaction pathway and accelerated the binding of
      substrates to the enzyme, especially the binding of isopentenyl diphosphate
      (IPP). When substrate concentrations are near the Km values, the rate-limiting
      step of the GGPP synthase reaction may be the substrate-binding step, probably
      the IPP-binding step, rather than the conversion step of the enzyme-farnesyl
      diphosphate-IPP complex to the enzyme-PPi-GGPP complex.

PMID- 8282732
TI  - Identification of an active dimeric form of aspartase as a denaturation
      intermediate.
AB  - The guanidine-HCl (Gu-HCl)-induced denaturation of a tetrameric enzyme, aspartase
      from Escherichia coli has been studied by size-exclusion chromatography, and
      circular dichroism and fluorescence spectroscopies. The size-exclusion analysis
      showed that in the presence of 0.4 M Gu-HCl, the enzyme has a dimeric structure
      with 45% of the native activity. The fluorescence and CD studies showed that only
      a small change occurred in the secondary and tertiary structures in 0.4 M Gu-HCl.
      In the range of 0.4 to 1 M Gu-HCl, decrease in the activity was observed as the
      secondary and tertiary structures were disrupted, whereas the dimeric enzyme did
      not dissociate into inactive monomer until 1 M Gu-HCl. When the enzyme was
      denatured in less than 1 M Gu-HCl, more than 90% of the original activity was
      recovered from the renaturation reaction, indicating that the dissociation
      process from tetramer to dimer is reversible. In contrast, the renaturation yield
      was 43% when the enzyme was diluted from more than 1 M Gu-HCl, indicating that
      the process of dissociation into monomer is not reversible. Thus, we identified
      an active dimeric form as a denaturation intermediate in this study, although the
      intermediates (including dimer) that were detected in renaturation experiments at
      low temperature were inactive, as reported previously [Imaishi, H., Yumoto, N., &
      Tokushige, M. (1989) Physiol. Chem. Phys. Med. NMR 21, 221-228].

PMID- 8282733
TI  - Thermodynamic and kinetic stabilities of hen-egg lysozyme and its chemically
      modified derivatives: analysis of the transition state of the protein unfolding.
AB  - For the stabilization of a protein against irreversible denaturation caused by
      rapid reaction of the unfolded form of the protein (kinetic stabilization), the
      free energy change of activation for unfolding should be increased. First, we
      demonstrated that this strategy was effective to stabilize a protein against
      protease digestion. For kinetic stabilization, it is important to stabilize a
      protein at a site where the local structures are largely unfolded in the
      transition state for unfolding. We developed a method to find such sites by
      comparison of the thermodynamic stabilities and the unfolding rate constants
      between unmodified and modified proteins. Application of this method to analyze
      the transition state of hen-egg lysozyme using some chemically modified
      derivatives is also described. Moreover, it was confirmed that the protease
      digestion method is superior to the relaxation method for estimation of the
      unfolding rate constant. Namely, the protease digestion method may be useful in
      analyzing the transition state of protein unfolding.

PMID- 8282734
TI  - Phospholipid fatty acid compositions of hepatopancreas and muscle from the prawn,
      Penaeus japonicus.
AB  - The hepatopancreas and muscle of the prawn, Penaeus japonicus, were analyzed as
      to the phospholipid fatty acid composition. The most important lipids in the
      hepatopancreas are triglycerides and phospholipids, while the lipids in muscle
      are principally phospholipids and free cholesterol. Fatty acids such as palmitic
      (16:0), stearic (18:0), oleic (18:1 n-9), eicosapentaenoic (20:5 n-3), and
      docosahexaenoic (22:6 n-3) were prominent in the total phospholipid fatty acid
      composition. However, phosphatidylethanolamine appeared to be particularly rich
      in n-3 polyunsaturated fatty acids, sphingomyelin in saturated fatty acids
      (mainly 18:0), and phosphatidylinositol in monounsaturated fatty acids (mainly
      18:1 n-9). Our data indicated that each phospholipid class is characterized by a
      specific paraffin chain composition.

PMID- 8282735
TI  - Molecular cloning of the guinea-pig histamine H1 receptor gene.
AB  - The histamine H1 receptor gene was isolated from a guinea-pig gene library. The
      gene contains no introns and encodes a protein of 488 amino acid residues. The
      structure of the guinea-pig histamine H1 receptor is predicted to contain seven
      putative transmembrane regions, which are similar to those of receptors coupling
      with GTP binding proteins. Although the third intracellular domain, the predicted
      binding site for the GTP binding protein, showed only 50% identity with those of
      the bovine and rat H1 receptors, the expressed guinea-pig H1 receptor was fully
      able to bind with [3H]mepyramine. Northern blot analysis indicated that the
      cerebrum, cerebellum, lung, adrenal, intestine, and heart expressed 3.3 kb guinea
      pig H1 receptor mRNA. Expression of histamine H1 mRNA of guinea-pig peripheral
      organs was greater than that of rat organs, suggesting the high sensitivity of
      guinea-pig organs as to histamine is due to the contents of histamine H1 receptor
      mRNA. In addition, the lung, adrenal, intestine, and heart expressed 3.9 kb mRNA.
      In situ hybridization showed that the hippocampus, cerebral cortex, thalamus, and
      granular layer of the cerebellum each contained a large amount of histamine H1
      receptors. Southern blot analysis showed that there was another gene quite
      similar to the cloned histamine H1 receptor gene.

PMID- 8282736
TI  - Cholesteryl ester synthesis and hydrolysis in the rat mammary gland during
      pregnancy and lactation.
AB  - The activities of a lysosomal acid and two neutral cholesteryl ester hydrolases
      (microsomal and cytosolic) found in the mammary gland were studied in subcellular
      fractions prepared from tissue from rats at various stages of pregnancy,
      lactation, and after weaning the pups. The relationship between the activities of
      these enzymes and that of acyl coenzyme A: cholesterol acyl transferase (ACAT)
      was also investigated. Acid cholesteryl ester hydrolase activity was increased
      considerably in glands from lactating as compared to pregnant animals, and was
      sharply decreased 2 days after weaning. The microsomal neutral cholesteryl ester
      hydrolase activity followed a similar pattern, but took longer to return to pre
      lactating values on weaning. In contrast, the activity of the cytosolic neutral
      cholesteryl ester hydrolase increased throughout pregnancy, then remained
      relatively constant in lactation and for 2 days after weaning. At 8 days post
      weaning, however, activity was markedly decreased. No correlation between the
      changes in the activities of any the cholesteryl ester hydrolases and ACAT during
      mammary gland development was detected. The microsomal neutral cholesteryl ester
      hydrolase activity showed a strong positive linear correlation with the
      unesterified and esterified cholesterol content of the microsomal fraction. No
      relationship, however, was found between the cytosolic neutral cholesteryl ester
      hydrolase and the level of either form of cholesterol in the cytosol. In
      addition, there was no correlation between ACAT activity and microsomal
      cholesterol concentrations. These results provide evidence for an important role
      for the enzymes responsible for cholesteryl ester synthesis and hydrolysis in the
      mammary gland in the regulation of cholesterol metabolism and the provision of
      cholesterol for secretion into milk.

PMID- 8282737
TI  - Secondary structure and protein folding of recombinant chloroplastic thioredoxin
      Ch2 from the green alga Chlamydomonas reinhardtii as determined by 1H NMR.
AB  - The recombinant form of the chloroplastic thioredoxin Ch2 from the green alga
      Chlamydomonas reinhardtii [Jacquot et al. (1992) Nucleic Acids Res. 20, 617] that
      preferentially activates the NADP dependent malate dehydrogenase [EC 1.1.1.82] (m
      type thioredoxin) through a light promoted reductive system, has been subjected
      to an extensive two-dimensional 1H NMR analysis. A complete 1H NMR assignment of
      the resonance lines in both the oxidized and the reduced states at pH 5.8 has
      been obtained allowing the recognition of the secondary structure patterns and
      the global protein folding. The single polypeptide chain, made of 106 residues
      plus one additional Met located at the N-terminal position (11.6 kDa) due to the
      protein expression system, folds into a pattern characteristic of the open
      twisted alpha/beta structures already found for Escherichia coli and human
      thioredoxins for which the protein shares 46 and 20% of sequence identity,
      respectively. The open alpha/beta structure is made of 5 beta-sheets associated
      in a parallel (beta 1 to beta 3) and anti parallel manner (beta 3 to beta 5) and
      surrounded by 4 helices. This represents the first structural exploratory study
      of the ubiquitous oxido-reductase thioredoxins in a photosynthetic living system.

PMID- 8282738
TI  - Reconstitution of rabbit skeletal muscle troponin from the recombinant subunits
      all expressed in and purified from E. coli.
AB  - Three subunits of rabbit skeletal muscle troponin were expressed in and purified
      from Escherichia coli. The procedures were optimized, and the reconstituted
      troponin complex is highly homogeneous, stable, and obtainable in large
      quantities, allowing us to conduct crystallization studies of the troponin
      complex. The three subunits expressed and purified are beta-TnT(N'-208),
      TnI(C64A, C133S), and the wild type TnC. beta-TnT(N'-208) is a 25 kDa fragment of
      beta-troponin T, which consists of 208 amino acids and lacks 58 residues in the N
      terminal variable region. TnI(C64A, C133S) is a mutant troponin I, in which Cys
      64 and Cys-133 are replaced by Ala and Ser, respectively. Each subunit was
      separately expressed in E. coli, purified by column chromatography including
      HPLC, and reassembled to form troponin complex. The reconstituted troponin
      complex was not distinguishable from authentic troponin prepared from rabbit
      skeletal muscle; the acto-S1 ATPase rate, as well as the superprecipitation, was
      calcium-sensitive. Small flat crystals up to 0.2 mm long have been reproducibly
      obtained in preliminary crystallization trials.

PMID- 8282739
TI  - Purification and characterization of a form of P450 from horse liver microsomes.
AB  - A form of P450 [termed P450(h-1)] was purified from the liver microsomes of a
      male horse to electrophoretic homogeneity. The specific content of the final
      P450(h-1) preparation was 14.8 nmol/mg of protein and the recovery was 0.38% of
      the microsomal P450. The apparent molecular weight of P450(h-1) was 52,000 Da.
      The absorption spectra of P450(h-1) indicated that P450(h-1) was a low- and high
      spin mixed type P450 in the oxidized form. The reconstituted system containing
      P450(h-1) could catalyze benzphetamine N-demethylation, 7-ethoxycoumarin O
      deethylation, and testosterone 16 alpha-hydroxylation. In the horse hepatic
      microsomes, aniline p-hydroxylation and testosterone 6 beta-hydroxylation, in
      addition to the above reactions, were detected. The N-terminal amino acid
      sequence of P450(h-1) was highly homologous to that of rat P450 2C11. Western
      blot analysis using anti-P450(h-1) antibody revealed that this antibody most
      strongly recognized P450 2C13 among ten rat P450s belonging to eight different
      subfamilies involved in hepatic drug metabolism. This anti-P450(h-1) antibody
      inhibited the testosterone 16 alpha-hydroxylase activity in horse liver
      microsomes. These results suggest that P450(h-1) belongs to the P450 2C subfamily
      and contributes to the testosterone 16 alpha-hydroxylation in horse liver
      microsomes.

PMID- 8282740
TI  - Behaviour of surgically corrected infrainguinal vein grafts.
AB  - During a period of 4 years (1988-1992) we detected in a series of 114
      infrainguinal vein grafts 22 bypasses (19%) with 26 hemodynamically significant
      (> 50%) stenoses. The secondary cumulative patency rate of 114 bypasses was 92%
      at 12, 84% at 24 and 84% at 36 months. Twenty-three secondary surgical procedures
      consisting of vein patch angioplasty (n = 10), interposition grafting (n = 3) or
      jump- or sequential grafting (n = 10) were performed to correct stenoses. One
      graft correction was technically not feasible, resulting in graft occlusion. Two
      patients refused surgery. All corrected grafts were prospectively studied both by
      ankle brachial measurements and color flow Duplex scanning every 3 to 6 months.
      Cumulative graft patency after reintervention in 20 grafts was 95% at 12 months
      and 95% at 24 months. Mild stenosis (< 50%) of revision sites was observed in 2
      grafts. No single stenosis remote of revision site developed during follow-up
      (mean 20.4 months), confirming the opinion that stenosed vein grafts after
      correction do not demonstrate a higher incidence to develop strictures than
      normal grafts. No tertiary procedures were necessary, as all categories of
      secondary procedures normalized graft and limb hemodynamics. This series
      demonstrates that excellent long term results after surgically corrected high
      grade graft lesions justify an aggressive approach to these stenoses.

PMID- 8282741
TI  - Anastomotic disjunction in long-term patent vascular synthetic grafts in Dacron.
AB  - This study follows the recently published paper on the in vivo behaviour of
      patent Dacron vascular prostheses and focuses in particular on anastomotic
      disjunction. The question of the evolution of anastomoses was tackled by
      examining its three basic components: prosthetic tissue, suture thread and
      arterial wall. The authors' observations were based on material taken from
      reoperations performed between 7 and 18 years after the first graft. These data
      enable the authors to affirm that the prosthesis undergoes a general physical and
      chemical deterioration which varies in intensity according to the type of
      weaving. On the contrary, in the anastomotic zone this phenomenon is not intense
      enough to jeopardize the anchorage of the suture thread since the original weft
      does not show any loss of compactness. In spite of surface morphological
      deterioration of various intensity, the suture threads maintain satisfactory
      mechanical properties and structural integrity. The artery wall in the
      anastomotic zone shows a massive degeneration in terms of its true anatomic
      structure responsible for the rupture of the suture rima. On the basis of these
      results the authors conclude that this phenomenon represents the "Achilles' heel"
      of anastomotic junction.

PMID- 8282742
TI  - Aortoesophageal fistula secondary to thoracic aortic aneurysm repair.
AB  - The development of a fistula between the aorta and the oesophagus after graft
      replacement of the thoracic aorta is extremely rare. We report a case which
      occurred 3 years and 7 months after repair of an aneurysm of the descending
      thoracic aorta and review the previous reports of this uniformly fatal condition.

PMID- 8282743
TI  - Aortic intussusception: a rare presentation of type A aortic dissection evidenced
      by transesophageal echocardiography.
AB  - Thoracic aorta dissection involving the ascending tract (type A) is an affection
      which can often become lethal. The possibility of reaching immediate diagnosis
      and setting up surgical treatment are fundamental for the patient prognosis. In
      the case report, trans-esophageal echocardiography (TEE) made it possible to
      reach an immediate diagnosis of an unusual presentation of the dissection of type
      A, the intussusception of the aorta, not diagnosed by other non invasive
      methodologies, thus permitting timely surgical treatment.

PMID- 8282744
TI  - Saphenous neuralgia and limb edema after femoropopliteal artery by-pass.
AB  - One hundred thirty-one limbs of 109 patients who underwent femoropopliteal artery
      by-pass were studied for postoperative saphenous neuralgia and limb edema. The
      following factors were analyzed: age, sex, underlying disease (arteriosclerosis
      obliterans or Buerger's disease), grade of symptoms (Fontaine's classification),
      presence of diabetes mellitus, the site of distal anastomosis (above or below the
      knee), vascular graft material (reversed saphenous vein, expanded
      polytetrafluoroethylene or composite), presence of postoperative hematoma, and
      levels of serum creatinine and albumin 3 weeks after surgery. To examine limb
      edema, radioisotope (RI) venography and RI lymphography were performed. Saphenous
      neuralgia occurred in 22 limbs (16.8%) and limb edema in 27 limbs (20.6%). None
      of the factors examined was found to be significantly associated with saphenous
      neuralgia. The risk of developing limb edema was higher in diabetic patients and
      in patients in whom the distal anastomosis was performed below the knee. Although
      no case of limb edema was associated with signs of obstruction on RI venogram,
      80% of the cases showed lymphatic obstruction on RI lymphograms.

PMID- 8282745
TI  - Femoral vein valve repair with limited anterior plication (LAP).
AB  - Limited anterior plication (LAP) of the incompetent femoral vein was used in 2
      groups of subjects with venous hypertension due to deep and superficial venous
      incompetence. Group 1 subjects were treated only with superficial veins surgery
      while groups 2 was treated with external valvuloplasty (LAP) at the level of the
      incompetent femoral vein. The plication was performed at the anterior side of the
      vein after limited dissection and manipulation. During a two-year follow-up the
      results of LAP were evaluated with color-duplex and ambulatory venous pressure
      (AVP) measurements. Nine of the 11 femoral veins treated with LAP were competent
      after 2 years (in 2 the incompetence was reduced). A lower AVP and RT was found
      in subjects treated with LAP in comparison with those in Group 1. Also the number
      of recurrent varicose veins (incompetent venous sites) and the average diameter
      of the femoral vein were higher in Group 2 (superficial surgery only). As no
      complications were observed LAP can be considered an alternative to the standard
      external valvuloplasty in cases of moderate incompetence when valve cusps are
      present and functional and incompetence is mainly due to relative enlargement of
      the vein diameter.

PMID- 8282746
TI  - Anomalous origin of the left coronary artery: a review of surgical management in
      13 patients.
AB  - Over the last decades, surgical management of anomalous left coronary artery
      originating from the pulmonary artery (ALCAPA) has seen a considerable evolution.
      Between 1965 and 1992, 13 children with age at operation ranging between 2 months
      and 11 years (mean 23 months) underwent one of 5 different surgical procedures:
      ligation (n = 3), direct aortic reimplantation (n = 7), subclavian (n = 1) or
      internal mammary (n = 1) artery anastomosis, or modified aortic implantation
      (Vigneswaran-procedure, n = 1). There were 3 early and one late deaths resulting
      in an overall mortality of 30.7%. Mortality was 66.7% in the ligation group, and
      20% in the revascularization group (28.6% in the subgroup with direct aortic
      implantation). The one late death occurred 6 months after ligation. Follow-up
      ranges between 3 months and 21 years, mean 7.3 years. All but one survivors are
      in NYHA functional class I. Following operative correction, there was clear
      improvement in left ventricular performance. Our data give reason to suggest
      ALCAPA to be more frequent than considered so far. Early surgery is recommended
      in all patients with ALCAPA, regardless of age or symptomatic status.
      Reestablishment of a two-coronary system is considered the procedure of choice.
      All survivors require long-term follow-up controls of early recognition of
      residual or progressive cardiac problems.

PMID- 8282747
TI  - The Monostrut prosthetic valve. Predictors for valve-related events during an
      eight years' experience.
AB  - All postoperative complications, including transient ischaemic attacks (TIA) and
      cerebrovascular accidents (CVA) of 259 patients, in whom a total of 301 Monostrut
      tilting-disc valves were implanted between January 1985 and December 1991 were
      evaluated retrospectively. The follow-up was maximally 8 years, with a mean of
      3.5 years, and totaled 914 patient-years. In this study we found no mechanical
      deterioration of the Monostrut valve and demonstrated the elimination of valve
      thrombosis in patients receiving adequate anticoagulation. The actuarial
      probability of being free of thrombo-embolism was 94.7% +/- 1.7% and free of
      anticoagulant related hemorrhage 95.4% +/- 1.5% at 8-years. In comparison with
      earlier reports by others, our findings show a lower ratio of thromboembolic and
      hemorrhagic events. We demonstrated a correlation (p < 0.05) between thrombo
      embolic and hemorrhagic complications. In addition, a lower incidence of CVA's
      (0.22 per 100 patient-years), but a higher incidence of TIA's (0.66 per 100
      patient-years) in comparison with the general Dutch population was found. At
      eight years follow-up, all patients were in Class I or II of the New York Heart
      Association Classification. Although the overall valve related event-free
      survival at eight years was only 47.9%, 93.5% of the patient were satisfied with
      their operative result. Predictive factors for late mortality were the occurrence
      of paravalvular leakage (p < 0.01), the age of the patient at the time of
      operation (p < 0.01) and the number of diseases coronary arteries (p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282748
TI  - Warm body, cold heart: myocardial revascularization in 2383 consecutive patients.
AB  - Systemic hypothermia is used almost universally in cardiac surgery. Since 1987,
      2383 patients underwent normothermic cardiopulmonary bypass (NCPB, "warm body",
      bladder temperature 36 degrees C) with cold blood cardioplegic arrest ("cold
      heart", 8-14 degrees C) during myocardial revascularization. No patients were
      denied this technique regardless of age, condition or severity of surgery.
      Clinical characteristics in patients: Age range: 31-92 years, mean 66;
      male/female ratio 3:1; pump time (min): 23-228, mean 80; cross clamp time (min):
      18-152, mean 60. One thousand, one hundred and sixty-one patients (49%) had
      urgent coronary artery bypass grafting (CABG). Ejection fraction was less than
      0.4 in 843 patients (30%). Thirty-day operative mortality was 1% (23/2383
      patients). Postoperative complications were: perioperative myocardial infarction
      (35 patients) = 1.5%; postoperative bleeding requiring reexploration (33
      patients) = 1.4%; stroke (22 patients) = 0.9%; mediastinal infection (24
      patients) = 1%; and renal insufficiency (25 patients) = 1%. During NCPB (warm),
      systemic vascular resistance was extremely low, cardiac output was high and it
      was easier to wean patients from the pump. No patient required the intraaortic
      balloon pump during peri- and post-operative periods. Pulmonary complications and
      coagulopathy were extremely rare. These results provide reassurance that NCPB
      (warm) in combination with cold cardioplegic arrest provides excellent myocardial
      and total body protection during myocardial revascularization and is particularly
      suitable for high-risk patients.

PMID- 8282749
TI  - Protective effects of oxygenated St. Thomas' Hospital cardioplegic solution
      during ischaemic cardiac arrest: improved function, metabolism and
      ultrastructure.
AB  - The isolated working rat heart model was use to define the cardioprotective
      effects (function, metabolic and ultrastructure) of the oxygenated St. Thomas'
      Hospital No. 2 cardioplegic solution (STH) during lengthy, hypothermic ischaemia
      (20 degrees C, 4 hours and 5 hours). Hearts (n = 9 for each group) were arrested
      with and exposed to multidose reinfusion (2 min every 40 min interval) throughout
      the ischaemic period with the cold (4 degrees C) STH or oxygenated (95% O2:5%
      CO2) STH. Oxygenated STH significantly (p < 0.01) improved the postischaemic
      recovery of cardiac output from 49.5 +/- 11.1% to 96.8 +/- 1.5% (in 4 hours) and
      from 20.3 +/- 7.2% to 72.2 +/- 5% (in 5 hours). Other indices of functional
      recovery showed similar improved performance with the significant decrease in
      time from the onset of reperfusion to the return of regular sinus rhythm (57 +/-
      8 v 495 +/- 150 s). The efflux of lactate during 5 hr ischaemic arrest was
      decreased (20.62 +/- 1.3 v 26.18 +/- 1.73 mumol/heart for oxygenated STH and STH,
      respectively, p < 0.05) and the progressive increase in the coronary vascular
      resistance was abolished in the oxygenated STH treated hearts. These improvements
      were associated with the reduction in the decline of the myocardial adenosine
      triphosphate (14.49 +/- 2 v 3.3 +/- 0.19 mumol/g dry wt), creatine phosphate
      (24.61 +/- 3.47 v 7.48 +/- 1.34 mumol/g dry wt) and guanosine triphosphate (1.69
      +/- 0.2 v 0.84 +/- 0.08 mumol/g dry wt) during ischaemia, total resynthesis after
      reperfusion (ATP: 103% v 36%, CP: 105% v 69% and GTP: 203% v 61% of control) and
      the total absence of myocardial cells and microvasculature injuries in ischaemic
      (non-reperfused) hearts. These results confirm that the provision of additional
      oxygen to the St. Thomas' Hospital solution (with 95% O2:5% CO2) can meet the
      metabolic demand of the ischaemic myocardium and thus increase the safe duration
      of cardiac arrest.

PMID- 8282750
TI  - Single-dose versus multi-dose cardioplegia in the immature rat heart: studies
      with normothermic and hypothermic ischemia.
AB  - The efficacy of cardioplegia in the neonatal heart has been questioned and some
      studies have suggested that, in the rabbit, multi-dose hypothermic cardioplegia
      may be damaging. We have therefore compared the protective properties of multi
      dose and single-dose cardioplegia in the immature rat heart with normothermic and
      hypothermic ischemia. Isolated Langendorff perfused hearts (n = 6 per group) from
      8-10 day-old rats, were arrested with a single-dose (2 min at the onset of
      ischemia) or multi-dose (2 min at onset of ischemia and repeatedly throughout
      ischemia) of warm (37 degrees C) or cold (10 degrees C) St Thomas' Hospital
      cardioplegic solution. The hearts were then subjected to 1 h of normothermic
      global ischemia or 24 h of hypothermic ischemia, followed by normothermic
      reperfusion of 30 min. In the normothermic studies the post-ischemic recovery of
      left ventricular developed pressure was 44 +/- 6% of its pre-ischemic value with
      single-dose cardioplegia versus 56 +/- 4% with multi-dose (cardioplegic infusion
      every 15 min). In the hypothermic studies the trend was in the opposite
      direction; the postischemic recovery of left ventricular developed pressure was
      46 +/- 2% in the single-dose group, whereas in the multi-dose (cardioplegic
      infusion every 6 h) group the recovery was 28 +/- 3% (p < 0.05). Thus, in accord
      with other studies in other species we have demonstrated that multi-dose
      cardioplegia fails to afford any substantial additional protection when compared
      with single-dose cardioplegia. Under conditions of extended hypothermia there may
      even be a detrimental effect of multi-dose cardioplegia.

PMID- 8282751
TI  - Hemodynamic alterations in venous blood flow produced by external pneumatic
      compression.
AB  - Venous stasis associated with prolonged bed rest can enhance the risk of deep
      venous thrombosis (DVT). Pneumatic compression of the lower extremities can
      reduce this risk by preventing venous stasis. When selecting a method of leg
      compression for their patients, physicians must chose between two distinctly
      different types of compression devices. One device applies pressure with a single
      chambered sleeve to the below knee region while the other applies pressure in a
      sequential gradient fashion from the ankle to the thigh. The current prospective
      study was designed to evaluated the ability of two such devices to increase blood
      flow in the profunda femoral vein. Venous blood flow velocity, compression time,
      and vein diameter were measured in nine normal experimental subjects using an
      Accuson duplex-Doppler before, during and after leg compression. Compression with
      the single-chambered device produced a significant rise in venous blood flow
      velocity; however, this could not be maintained and our results indicate a higher
      average velocity was achieved with the sequential gradient device. The sequential
      gradient device also moved a greater volume of blood and achieved a higher
      average blood flow rate. The time between deflation of the sleeve and return of a
      phasic respiratory signal was greater after compression with the sequential
      gradient device. These results suggest that sequential gradient compression
      produces the type of hemodynamic alterations needed to reduce the risk of DVT by
      achieving a sustained increase in venous blood flow and more completely emptying
      of the veins in the leg.

PMID- 8282752
TI  - Interactions between neutrophils and endothelial cells.

PMID- 8282753
TI  - Calcium homeostasis in plants.

PMID- 8282754
TI  - Is the gap junction channel--the connexon--made of connexin or ductin?

PMID- 8282755
TI  - The differentiation and lineage development of goblet cells in the murine small
      intestinal crypt: experimental and modelling studies.
AB  - The objective of this study was to provide a new insight into the origin and
      lineage development of mucus-producing cells in the small intestinal crypt. For
      this, new experimental data were obtained from both crypt sections and whole
      mounts. Model simulation studies were undertaken to investigate which rules are
      most likely to govern the dynamic cellular development and goblet cell pedigree.
      We have measured the frequency of mucus-secreting goblet cells (using alcian blue
      and periodic acid Schiff's stains) at each cell position in the ileal murine
      crypt. These measurements, made on sections, overestimate the number of goblet
      cells because of the size and centripetal position of the stained cytoplasm. The
      correction factor for this overscoring has been measured to be 0.25 by two
      independent methods. The data suggest that there are about 12 functional goblet
      cells per crypt many of which retain an ability to divide. We have also
      determined the labelling index of the crypt goblet cells at each cell position.
      Spatially, goblet cells exhibit a small degree of clustering in the crypt and
      show a good mixture with columnar cells. We have adapted our earlier dynamic
      matrix-based computer stimulation model to take into account goblet cell
      differentiation. The modelling suggested the following conclusions: firstly,
      goblet cells do not have their own stem cells but share a common stem cell with
      the columnar cells; secondly, the goblet lineage differentiates from the transit
      population two to three generations before the end of the lineage; and thirdly,
      the decision to switch on goblet properties is stochastic at a specific step in
      the development of columnar cells.

PMID- 8282756
TI  - Lipid and membrane protein transfer from human neutrophils to schistosomes is
      mediated by ligand binding.
AB  - Attachment of human neutrophils to schistosomula of Schistosoma mansoni involves
      leukocyte receptors recognizing carbohydrate, complement and/or IgG ligands on
      the parasite surface. Here, we examined the transfer of a fluorescent fatty acid
      analog (BOFA) from human neutrophils to schistosomula coated with concanavalin A
      (Con A), immune serum or nonimmune serum under co-culture conditions by
      fluorescence confocal laser scanning microscopy (CLSM). Coating schistosomes with
      Con A or immune serum and co-culturing them for 24 hours with BOFA-labeled
      neutrophils resulted in a specific lipid transfer to the surface tegument of the
      schistosomes. Tegumental labeling was absent when nonimmune serum was used. No
      significant difference (P < 0.001) was found in the number of neutrophils bound
      to the worm surface between Con A-coated schistosomes (4.1 +/- 0.345 cells/worm)
      and worms incubated in immune serum (4.261 +/- 0.362). The number of neutrophils
      bound to the schistosomula (2.7 +/- 0.223) was significantly reduced in the
      presence of nonimmune serum (P < 0.0001). The viability of the schistosomula was
      98% in nonimmune treated co-cultures, and 91% in cocultures treated with immune
      serum. HPLC analysis of labeled neutrophils demonstrated that BOFA was
      incorporated into both phospholipids and neutral lipids, which were almost
      exclusively triglycerides and, after 18 hours of culture, all of the fatty acid
      analog was incorporated into complex lipids. Double-label experiments in which
      schistosomula bearing Con A were first incubated with BOFA-labeled neutrophils
      and subsequently immunolabeled revealed that the neutrophil membrane proteins,
      MHC class I, CR1 and CR3 were co-transferred with neutrophil lipids to the
      parasite tegument.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282757
TI  - Commitment of the teratocarcinoma-derived mesodermal clone C1 towards terminal
      osteogenic differentiation.
AB  - The mesodermal clone C1 was derived from the multipotent embryonal carcinoma 1003
      cell line transformed with the plasmid pK4 carrying SV40 oncogenes under the
      control of the adenovirus E1A promoter. We have shown that the C1 clone becomes
      committed to the osteogenic pathway when cultured in aggregates in the presence
      of mediators of the osteogenic differentiation. To further validate C1 as a model
      with which to study osteogenesis in vitro the kinetics of its differentiation was
      studied, focusing on the histology of the aggregates and on the expression of a
      set of genes corresponding to representative bone matrix proteins. The presence
      of ascorbic acid and beta- glycerophosphate specifically leads to mineralization
      in almost 100% of the aggregates. Transcription of the above genes, silent in
      exponentially growing cells, specifically occurred with the establishment of cell
      cell contacts independently of the presence of ascorbic acid and inorganic
      phosphate. The latter, however, were absolutely required for matrix deposition
      and mineralization. In their presence, one observed an overall decline in type I
      collagen and alkaline phosphatase transcripts while osteocalcin and osteopontin
      transcripts preferentially accumulated in cells lining the mineralizing foci.
      Concomitantly, type I collagen and osteocalcin became extracellularly deposited.
      The osteogenic differentiation of C1 occurred while cells were still
      proliferating. The C1 clone thus behaves as a mesodermal stem cell, becoming
      committed to the osteogenic pathway upon: firstly, establishment of cellular
      contacts; and secondly, addition of ascorbate and beta-glycerophosphate. It
      therefore appears to be a promising in vitro system for deciphering the molecular
      basis of osteoblast ontogeny.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282758
TI  - Phorbol ester-induced scattering of HT-29 human intestinal cancer cells is
      associated with down-modulation of E-cadherin.
AB  - The effects of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on the
      growth characteristics of the colon cancer cell line HT-29 M6 were studied. TPA
      induced the scattering of proliferative HT-29 M6 cells: in the presence of the
      phorbol ester, HT-29 M6 colonies scattered and the cells acquired a flatter
      aspect with diminished cell-cell contacts. This effect of TPA required a
      persistent activation of PK-C and was accompanied by a slight decrease (30%) in
      the growth rate. Modifications by TPA of two scattering associated properties of
      these cells were also detected: TPA decreased cell-to-cell aggregation and
      enhanced the cellular attachment to matrix substrata (collagen, laminin). The
      decrease in cell-to-cell adhesion was correlated with a loss of cellular E
      cadherin as evidenced by immunofluorescence or immunoblotting with a specific
      monoclonal antibody. Cell scattering was dependent on the extracellular
      concentration of Ca2+; an increase from 1.6 to 10 mM in the concentration of this
      ion completely blocked the morphological effects of TPA as well as its action on
      cell aggregation. This high concentration of Ca2+ also prevented the down
      modulation of E-cadherin as determined by immunofluorescence. However, the TPA
      induced increase in cell attachment to the matrix was not affected by high
      calcium. These findings support the importance of altered cell-cell adhesion in
      the process of scattering and provide a good system for the study of down
      modulation of E-cadherin, a protein involved in the control of cell growth,
      differentiation and invasion of epithelial cells.

PMID- 8282759
TI  - Calcium buffer injections inhibit cytokinesis in Xenopus eggs.
AB  - A slow cortical wave of high calcium accompanies the elongation of cleavage
      furrows in medaka fish eggs as well as in Xenopus eggs. We explored the role of
      such waves by injecting calcium buffers into Xenopus eggs at various times before
      and during first and second cleavage. Injection earlier than about 15 minutes
      before first cleavage normally starts delays it for hours. Injection between
      about 15 minutes and a few minutes before cleavage normally starts allows a
      (short) furrow to form on time but usually yields an eccentric one. This forms
      away from the injection side, often as far off-center as the egg's equator, and
      then regresses. Injection soon after it starts quickly arrests elongation of the
      furrow and eventually induces its regression; while injection a bit later
      likewise soon arrests elongation but allows delocalized furrow deepening to
      continue. The dependence of these inhibitory actions upon the dissociation
      constants and final cytosolic concentrations of the injected buffers indicates
      that they act as shuttle buffers to suppress needed zones of high calcium in the
      micromolar range. We conclude that the high calcium that is found within these
      furrows is needed to induce them, to extend them and even to maintain them.
      Moreover, while short, eccentric furrows often form as far off center as the
      equator, they somehow always form along a meridian through the animal pole. This
      seems difficult to explain by the orthodox, diastral model. Rather, it suggests
      that the cleavage furrows in Xenopus--and perhaps in animal cells quite generally
      -are directly induced by a diastema or telophase disc rather than by the asters.

PMID- 8282760
TI  - Nuclear localization of vertebrate cyclin A correlates with its ability to form
      complexes with cdk catalytic subunits.
AB  - Cyclins control the activities of cyclin-dependent protein kinases (cdks) and
      hence play a key role in cell cycle regulation. While B-type cyclins associate
      with p34cdc2 to trigger entry into mitosis, progression through S phase requires
      cyclin A, presumably in association with p33cdk2. Vertebrate A- and B-type
      cyclins display strikingly distinct subcellular localizations, but the mechanisms
      underlying these differential distributions are unknown. Here, we have begun to
      study the requirements for nuclear localization of cyclin A. We have isolated a
      cDNA coding for chicken cyclin A and constructed a series of deletion mutants.
      These were then transfected into HeLa cells, and the subcellular distribution of
      the mutant cyclin A proteins was determined by indirect immunofluorescence
      microscopy. In parallel, the cyclin A mutants were assayed for their ability to
      form complexes with cdk subunits. We found that deletion of more than 100
      residues from the N terminus of cyclin A did not impair nuclear localization or
      cdk subunit binding and kinase activation. In contrast, removal of as few as 15
      residues from the C terminus, or deletion of part of the internal cyclin box
      domain, abolished nuclear localization of cyclin A as well as its ability to bind
      to and activate cdk subunits. These results suggest that nuclear transport of
      cyclin A may depend on the formation of multiprotein complexes comprising cdk
      catalytic subunits.

PMID- 8282761
TI  - Cloning of the polyubiquitin cDNA from the marine sponge Geodia cydonium and its
      preferential expression during reaggregation of cells.
AB  - Ubiquitination of proteins is a critical step in the controlled degradation
      process of many polypeptides. Here we show that sponges, the simplest
      multicellular group of eukaryotic organisms, are also equipped with the ubiquitin
      pathway. The polyubiquitin cDNA was isolated and characterized from the marine
      sponge Geodia cydonium. The open reading frame contains six ubiquitin moieties,
      which are lined up head to tail without spacers. A comparison of the predicted
      amino acid sequence of the six sponge ubiquitin-coding units with those from
      other organisms revealed a high degree of homology (> 93%). The ubiquitin gene is
      expressed to almost the same extent in the two main compartments of the sponge,
      the cortex and the medulla. However, only in the cortex are detectable amounts of
      the ubiquitin protein synthesized. The ubiquitin protein isolated from the sponge
      organism was found to initiate protein degradation in the heterologous
      reticulocyte system in the same manner as bovine ubiquitin. In vitro studies with
      dissociated sponge cells revealed that the homologous aggregation factor causes
      (i) a strong increase in the steady-state level of mRNA coding for ubiquitin and
      (ii) a drastic increase in ubiquitin protein synthesis, while the homologous
      lectin failed to display that effect in isolated cells. These data suggest that
      ubiquitin may play a role in sponge morphogenesis.

PMID- 8282762
TI  - Organelle movements in the wild type and wall-less fz;sg;os-1 mutants of
      Neurospora crassa are mediated by cytoplasmic microtubules.
AB  - The cellular basis of organelle transport in filamentous fungi is still
      unresolved. Here we have studied the intracellular movement of mitochondria and
      other organelles in the fungus Neurospora crassa. Four different model systems
      were employed: hyphae, protoplasts, a cell wallless mutant, and experimentally
      generated small, flattened cell fragments of the mutant cells. Organelle
      movements were visualized by DIC optics and computer-enhanced video microscopy.
      In all cell models the transport of organelles was vectorial and saltatory in
      nature. The mean velocities for mitochondria, particles and nuclei were 1.4, 2.0,
      and 0.9 microns/s, respectively. Treatment with 10 microM nocodazole for 30
      minutes caused a complete disappearance of microtubules and reversibly blocked
      directed transport of virtually all organelles, whereas cytochalasin D up to 20
      microM was without effect. Correlative video and immunofluorescence microscopy of
      small fragments of wall-less mutant cells revealed a clear match between
      microtubule distribution and the tracks of moving organelles. We conclude that
      organelle movement in the filamentous fungus Neurospora crassa is a microtubule
      dependent process.

PMID- 8282763
TI  - Alpha 7 beta 1 integrin is a component of the myotendinous junction on skeletal
      muscle.
AB  - Immunization against a 70 kDa band that co-purifies with skeletal muscle
      integrins has resulted in an antibody directed against the avain alpha 7 integrin
      subunit. The specificity of the antibody was established by patterns of tissue
      staining and cross-reactivity with antibodies directed against the cytoplasmic
      domain of the rat alpha 7 cytoplasmic domain. On sections of adult skeletal
      muscle the alpha 7 integrin was enriched in the myotendinous junction (MTJ). This
      localization was unique as neither the alpha 1, alpha 3, alpha 5, alpha 6 and
      alpha v subunit localizes in the myotendinous junction. The distribution of the
      alpha 7 subunit in the MTJ was examined during embryonic development. alpha 7
      expression in the junction is first apparent around embryo day 14 and is almost
      exclusively at the developing MTJ at this stage. alpha 3 is expressed with
      distinctive punctate staining around the junctional area in earlier embryos (11
      day). The time of appearance of the alpha 7 subunit in the MTJ correlates with
      the insertion of myofibrils into subsarcolemmal densities and folding of the
      junctional membrane, suggesting a role of the alpha 7 integrin in this process.
      Vinculin is present throughout development of the myotendinous junction,
      suggesting that the alpha 7 integrin recognizes a preformed cytoskeletal
      structure. The presence of the alpha 7 subunit in the myotendinous junction and
      the alpha 5 subunit in the adhesion plaque demonstrates a molecular difference
      between these two adherens junctions. It also points to possible origins of
      junctional specificity on muscle. Differences between these two junctions were
      developed further using an antibody against phosphotyrosine (PY20).
      Phosphotyrosine is thought to participate in the organization and stabilization
      of adhesions. The focal adhesion and the neuromuscular junction, but not the MTJ,
      contained proteins phosphorylated on tyrosine.

PMID- 8282764
TI  - The role of cyclic GMP in regulating myosin during chemotaxis of Dictyostelium:
      evidence from a mutant lacking the normal cyclic GMP response to cyclic AMP.
AB  - Evidence has previously been reported that, during chemotaxis of the cellular
      slime mould Dictyostelium discoideum, cyclic GMP regulates the association of
      myosin II with the cytoskeleton and that this regulation is effected by
      inhibiting myosin II heavy chain phosphorylation (Liu and Newell, J. Cell Sci.,
      90, 123-129, 1988; 98, 483-490, 1991). Here we provide further evidence in
      support of this hypothesis using a mutant (KI-10) that is defective in chemotaxis
      and lacks the normal cyclic AMP-induced cyclic GMP response. We found that the
      cyclic AMP-induced cytoskeletal actin response was similar to that of the
      parental strain in this mutant (although showing a slight displacement in the
      dose-response curve) but the cytoskeletal myosin II heavy chain response was
      abolished. Moreover, the mutant showed no phosphorylation of myosin II heavy
      chain in response to cyclic AMP. Compared to the parental strain XP55, the mutant
      cells contained approximately 40% more protein and their doubling time was 30%
      longer. These differences could be due to differences in the efficiency of cell
      division, a process in which the proper regulation of myosin function is
      essential and in which cyclic GMP may therefore play a role.

PMID- 8282765
TI  - Characterization of a PC12 cell sub-clone (PC12-C41) with enhanced neurite
      outgrowth capacity: implications for a modulatory role of high molecular weight
      tau in neuritogenesis.
AB  - To address the means by which diversity of neuronal morphology is generated, we
      have isolated and characterized naturally occurring variants of rat PC12
      pheochromocytoma cells that exhibit altered neurite outgrowth properties in
      response to nerve growth factor (NGF). We describe here a PC12 cell sub-clone,
      designated PC12-clone 41 (PC12-C41), that displays significant increases in
      neurite abundance and stability when compared with the parental line. This
      difference does not appear to be due to an altered sensitivity or responsiveness
      to NGF or to a more rapid rate of neurite extension. Because of the role of the
      cytoskeleton in neuritogenesis, we examined a panel of the major cytoskeletal
      proteins (MAP 1.2/1B, beta-tubulin, chartins, peripherin, and high and low
      molecular weight (HMW and LMW) taus) whose levels and/or extent of
      phosphorylation are regulated by NGF in PC12 cultures. Although most cytoskeletal
      proteins showed little difference between PC12 and PC12-C41 cells (+/- NGF
      treatment), there was a significant contrast between the two lines with respect
      to tau expression. In particular, while NGF increases the total specific levels
      of tau in both cell types to similar extents (by about twofold), the proportion
      comprising HMW tau is threefold higher in the PC12-C41 clone than in PC12 cells.
      A comparable difference was observed under substratum conditions that were non
      permissive for neurite outgrowth and so this effect was not merely a consequence
      of the differential neuritogenic capacities of the two lines. The distinction
      between the expression of HMW and LMW taus in PC12 and PC12-C41 cells (+/- NGF)
      was also observed at the level of the messages encoding these proteins. Such
      findings indicate that initiation of neurite outgrowth in PC12 cultures does not
      require a massive induction of tau expression and raise the possibility that HMW
      and LMW taus may have differential capacities for modulating neuronal morphology.

PMID- 8282766
TI  - Incorporation of tubulin subunits into dimers requires GTP hydrolysis.
AB  - A toroid multisubunit complex of 800-900 kDa has been implicated in assisting
      protein folding of at least two cytoplasmic proteins, actin and tubulin. This
      process is dependent on the presence of magnesium ions and ATP hydrolysis. In
      vitro translation of cDNAs encoding different alpha- and beta-tubulin isotypes
      also gives rise to the formation of complexes of about 300 kDa. These complexes
      have been functionally implicated in the incorporation of tubulin monomers within
      the tubulin heterodimer. This work shows that, in addition to ATP hydrolysis, the
      incorporation of newly synthesized tubulin subunits into functional heterodimers
      requires GTP hydrolysis in the presence of magnesium ions. A two-step process is
      suggested, a first ATP-dependent step in which the 900 kDa complexes are
      implicated in a similar way to the step taking place in actin folding, and a
      second GTP-dependent step in which the 300 kDa complexes are involved in the
      assembly of the heterodimer.

PMID- 8282767
TI  - An isoform of microtubule-associated protein 2 (MAP2) containing four repeats of
      the tubulin-binding motif.
AB  - Microtubule-associated protein 2 (MAP2) exists in both high- and low-molecular
      mass isoforms, each of which has a tubulin-binding domain consisting of 3
      imperfect tandem repeats of 31 amino acids containing a more highly conserved 18
      amino acid 'core' sequence. We describe here a novel form of low molecular mass
      MAP2 (MAP2c) that contains an additional 4th repeat of this tubulin-binding
      motif. Like the 3 previously known repeat sequences, this 4th copy is highly
      conserved between MAP2 and the two other known members of the same gene family,
      tau and MAP4. In each of these three genes the additional 4th repeat is inserted
      between the 1st and 2nd repeats of the 3-repeat form of the molecule. Experiments
      with brain cell cultures, in which the relative proportions of neurons and glia
      had been manipulated by drug treatment, showed that 4-repeat MAP2c is associated
      with glial cells whereas 3-repeat MAP2c is expressed in neurons. Whereas 3-repeat
      MAP2c is expressed early in development and then declines, the level of 4-repeat
      MAP2c increases later in development, corresponding to the relatively late
      differentiation of glial cells compared to neurons. When transfected into non
      neuronal cells, the 4-repeat version of MAP2c behaved indistinguishably from the
      3-repeat form in stabilising and rearranging cellular microtubules. The presence
      of an additional 4th repeat of the tubulin-binding motif in all three members of
      the MAP2 gene family suggests that this variant arose prior to their
      differentiation from an ancestral gene.

PMID- 8282768
TI  - Inhibition of constitutive protein secretion from lactating mouse mammary
      epithelial cells by FIL (feedback inhibitor of lactation), a secreted milk
      protein.
AB  - The effect of a protein feedback inhibitor of lactation (FIL) on casein synthesis
      and secretion was examined using isolated acini from lactating mouse mammary
      gland. As previously found, FIL partially inhibited protein synthesis but
      produced an additional inhibition of constitutive casein secretion. The
      inhibition of synthesis and secretion showed similar dose-dependency and the
      inhibition was fully reversible. Constitutive secretion of pre-formed protein was
      inhibited by FIL in a pulse-chase protocol, indicating that the inhibitor
      regulated protein secretion by reducing protein movement through the secretory
      pathway independently of any initial inhibition of synthesis. Regulated
      exocytosis was not inhibited since casein release due to elevation of cytosolic
      Ca2+ concentration by the ionophore ionomycin was unaffected. Brefeldin A, which
      is known to block ER-to-Golgi transport, also inhibited both protein synthesis
      and secretion in mammary cells. The action of FIL on synthesis and secretion and
      previously described actions on casein degradation would be consistent with a
      block at an early stage in the secretory pathway. In support of this idea FIL
      treatment was found to result in vesiculation and swelling of the endoplasmic
      reticulum. These data provide evidence for a novel control of a constitutive
      secretory pathway by a physiological extracellular regulatory protein.

PMID- 8282769
TI  - Recycling of a secretory granule membrane protein after stimulated secretion.
AB  - Recycling of a secretory granule membrane protein, dopamine-beta-hydroxylase, was
      examined in primary cultures of bovine adrenal chromaffin cells. Cells were
      stimulated to secrete in the presence of antibodies directed against the luminal
      domain of dopamine-beta-hydroxylase. The location of the antibodies after various
      times of reincubation and after a second secretory stimulus was assessed using
      immunofluorescence microscopy. Stimulation led to the exposure of dopamine-beta
      hydroxylase at the plasma membrane, which could be detected by a polyclonal
      antibody in living and fixed cells. The plasma membrane dopamine-beta
      hydroxylase, either alone or complexed with antibody, was rapidly internalized
      after removal of the secretagogue. Internalized protein-antibody complex remained
      stable for at least 24 hours of reculture. Twenty four hours after stimulation
      the cells with internalized antibody could respond to further stimulation and
      some of the antibody was re-exposed at the plasma membrane. These findings were
      confirmed using FACS analysis. This suggests that the antibody-protein complex
      had returned to secretory granules that could respond to further secretagogue
      stimulation.

PMID- 8282770
TI  - Tumor spheroid-induced vesicle formation on endothelial cells is associated with
      procoagulant properties.
AB  - Fibrin deposits in tumor beds are an intriguing phenomenon. It has been suggested
      that fibrin plays a role as a provisional matrix in which the tumor grows and
      induces development of a vascular network. On the other hand fibrin possibly
      protects the tumor nodule from host defense mechanisms. We therefore investigate
      whether tumor cells can induce a procoagulant response in endothelial cells
      leading to fibrin formation. For our studies we employed a modification of the
      matrix model of Montesano in which sprouting of endothelial cell aggregates can
      be followed. This system allows us to study in vitro the involvement of
      coagulation in tumor growth and angiogenesis. Cocultures of endothelial cell
      aggregates and avascular tumor spheroids in collagen type I gels results in the
      appearance of extracellular vesicle-like structures on the endothelial sprouts.
      The vesicles formed on endothelial cell sprouts upon coculturing with tumor cells
      exhibit an increased amidolytic activity, suggestive of factor X/Xa activity, not
      dependent on tissue factor exposure. Experiments using HgCl2 and Iodoacetamide
      point to the importance of SH groups in the factor X/Xa activity on endothelial
      cell sprouts.

PMID- 8282771
TI  - Involvement of a phosphoprotein on the zymogen granule membrane in the control of
      regulated exocytosis in the exocrine pancreas.
AB  - The pancreatic acinar cell is one of a number of cell types in which
      phosphoproteins are believed to be involved in the control of regulated
      exocytosis. We have examined the effects of three agents that affect secretion in
      the acinar cell on the phosphorylation states of proteins on the zymogen granule
      membrane. We show that Ca2+ and GTP gamma S, which stimulate secretion, also
      stimulate the phosphorylation of a protein of M(r) 45,000 (p45) on isolated
      zymogen granules. On the other hand, the protein kinase inhibitor genistein
      inhibits both secretion and phosphorylation of p45. For all three agents, p45
      phosphorylation is affected over concentration ranges identical to those that
      affect secretion. The stimulatory effect of GTP gamma S and the inhibitory effect
      of genistein are also seen when the phosphorylation state of p45 on granules
      within permeabilized cells is examined. Ca2+, however, over the same
      concentration range, now causes dephosphorylation of p45. Furthermore, the time
      course of this effect is similar to that of Ca(2+)-triggered secretion.
      Phosphorylation of p45 is exclusively on serine, with no detectable
      phosphorylation on either threonine or tyrosine. We propose that exocytosis in
      pancreatic acini is controlled at least in part through the
      phosphorylation/dephosphorylation of p45, with dephosphorylation acting as a
      trigger for exocytosis.

PMID- 8282772
TI  - Brain-type creatine kinase in photoreceptor cell outer segments: role of a
      phosphocreatine circuit in outer segment energy metabolism and phototransduction.
AB  - Different isoforms of creatine kinase, an important enzyme of vertebrate energy
      metabolism, were localized in bovine photoreceptor cells, with particular
      emphasis on the identification and quantification of the brain-type isoform
      within the outer segment compartment. Using immunofluorescence and immunoelectron
      microscopy, brain-type creatine kinase was shown to be present in bovine
      photoreceptor cell outer and inner segments. The presence of this isoenzyme in
      rod outer segments was additionally confirmed by immunoblotting and
      immunolabeling of isolated rod outer segments. The content of creatine kinase in
      rod outer segments was quantified by measuring creatine kinase activity after
      membrane disruption with detergent. The ATP regeneration potential provided by
      the creatine kinase in isolated, washed bovine rod outer segments was 1.2 +/-
      (0.4) i.u. mg-1 rhodopsin. This value was calculated to be at least an order of
      magnitude larger than that necessary to replenish the energy required for cGMP
      resynthesis in rod outer segments, and high enough to regenerate the entire ATP
      pool of rod outer segments within the time span of a photic cycle. A
      mitochondrial creatine kinase isoenzyme was located within the ellipsoid portions
      of bovine rod and cone inner segments by immunofluorescence microscopy and, using
      immunogold staining, was specifically localized in the mitochondria clustered
      within bovine rod and cone inner segments. These results suggest that vertebrate
      photoreceptor cells contain a functional phosphocreatine circuit. Outer segment
      creatine kinase may play an important role in phototransduction by providing
      energy for the visual cycle, maintaining high local ATP/ADP ratios and consuming
      protons produced by enzymes located in the outer segment.

PMID- 8282773
TI  - Keratocyte networks visualised in the living cornea using vital dyes.
AB  - Fluorescent viability probes have been used to visualise and investigate the
      viability, morphology and organisation of the keratocyte within the stroma of the
      intact living cornea. The live cell probe, calcien-AM, in combination with a dead
      cell probe, ethidium homodimer (Live/Dead Assay, Molecular Probes, U.S.A.) proved
      superior to earlier generation vital dyes such as fluorescein diacetate or 5,6
      carboxyfluorescein diacetate, initially used in combination with ethidium
      bromide. The ubiquitous distribution of esterase enzymes that cleave calcien-AM
      within the keratocyte cytoplasm produced a high concentration of fluorescently
      active calcein throughout the cell, including fine cell processes. Epi
      illuminated fluorescence microscopy on transparent corneal dissections
      subsequently revealed details of keratocyte microanatomy and three-dimensional
      network organisation in situ. Three morphologically discrete subpopulations of
      keratocytes were identified: two formed relatively small bands of cells,
      immediately subjacent to either Bowman's or Descemet's membranes, the third
      subpopulation constituting the majority of keratocytes typically located within
      the corneal stroma. The results indicate that calcein-AM is able to penetrate
      intact living cornea revealing cell viability, and it also has the capacity to
      'trace' cellular elements and reveal fine structure within a dense connective
      tissue matrix.

PMID- 8282774
TI  - Osmoregulation in Paramecium: the locus of fluid segregation in the contractile
      vacuole complex.
AB  - In a previous study, monoclonal antibody DS-1 was found to specifically label the
      decorated spongiome along the radial arms of the contractile vacuole complexes in
      Paramecium multimicronucleatum. Fluorescein isothiocyanate-conjugated DS-1, when
      injected into cells, labels the radial arms initially, but with increasing
      postinjection time both the intensity of fluorescence and the number of
      fluorescently labeled radial arms were reduced. When these cells were fixed after
      45 minutes and probed indirectly using a second fluorochrome, little new label
      was seen on the already fluorescein-labeled radial arms. Thin sections showed
      that the amount of decorated tubules along some collecting canals decreased from
      the proximal to the distal end and vesicles, which were never seen in control
      cells, appeared next to the decorated spongiome. These results suggested that the
      decorated spongiome was undergoing disassembly and sequestration into one region
      of the cell. The injected DS-1 also reduced the expulsion frequency of the
      contractile vacuoles in a dose-, time- and site-dependent manner. The contractile
      vacuole complexes near the injection site were affected more than those farther
      from the site, but the sizes of both contractile vacuoles were only transiently
      affected so that fluid output per cell was reduced by approximately 60%. Beyond
      45 minutes postinjection, both the expulsion frequency and total fluid output
      began to recover as the DS-1 was sequestered into one part of the cell. This
      region persisted in cells up to 18 hours but disappeared by 24 hours, which
      coincided with the full recovery of the expulsion frequency and of decorated
      spongiome along the radial arms. The contractile vacuole, the collecting canals
      and the smooth spongiome were morphologically unaffected. These results indicate
      that when the decorated spongiome is dissociated from the contractile vacuole
      complex, the complex's function is strongly inhibited, showing the decorated
      spongiome to be the site of fluid segregation.

PMID- 8282775
TI  - Res Ipsa loquitur: positive and negative trends affecting the JCI.

PMID- 8282776
TI  - Interstitial insulin concentrations determine glucose uptake rates but not
      insulin resistance in lean and obese men.
AB  - Insulin action and obesity are both correlated with the density of muscle
      capillary supply in humans. Since the altered muscle anatomy in the obese might
      affect interstitial insulin concentrations and reduce insulin action, we have
      cannulated peripheral lymphatic vessels in lean and obese males, and compared
      peripheral lymph insulin concentrations with whole body glucose uptake during a
      euglycemic, hyperinsulinemic clamp. Lymph insulin concentrations in the lower
      limb averaged only 34% of arterial insulin concentrations during 150 min of
      insulin infusion. Obese subjects had the highest arterial (P < or = 0.0001) and
      lymph insulin (P < 0.005) concentrations, but the lowest glucose uptake rates (P
      < 0.002). In contrast to the initial steep rise then plateau of arterial
      insulins, both lymph insulin and whole body glucose uptake rates rose slowly and
      did not consistently reach a plateau. In each individual, the glucose uptake
      closely correlated with peripheral lymphatic insulin concentrations (mean r2 =
      0.95). The coupling between glucose uptake and lymph insulin (glucose uptake/pmol
      insulin) was much steeper in lean subjects than in the obese (P < or = 0.0001).
      These results indicate that even if insulin diffusion into tissues is rate
      limiting for insulin action, a tissue defect rather than an insulin diffusion
      defect causes insulin resistance in obese subjects.

PMID- 8282777
TI  - Na+/H+ exchangers, NHE-1 and NHE-3, of rat intestine. Expression and
      localization.
AB  - Na-H exchange (NHE) is one of the major non-nutritive Na absorptive pathways of
      the intestine and kidney. Of the four NHE isoforms that have been cloned, only
      one, NHE-3, appears to be epithelial specific. We have examined the regional and
      cellular expression of NHE-3 in the rat intestine. NHE-3 message in the small
      intestine was more abundant in the villus fractions of the small intestine than
      in the crypts. Analysis of NHE-3 mRNA distribution in the gut by in situ
      hybridization demonstrated epithelial cell specificity, as well as expression
      preferential to villus cells. NHE-1 message, in contrast, was ubiquitous, with
      slightly greater expression exhibited in the differentiating crypt and lower
      villus cells of the small intestine. Isoform-specific NHE-3 fusion protein
      antibody identified a 97-kD membrane protein in the upper villus cells of the
      small intestine, which was exclusively localized in the apical membrane. In
      contrast, antibody previously developed against the COOH-terminal region of human
      NHE-1 (McSwine, R. L., G. Babnigg, M. W. Musch, E. B. Chang, and M. L. Villereal,
      manuscript submitted for publication) identified a 110-kD basolateral membrane
      protein. These data suggest that unlike NHE-1, which probably serves a
      "housekeeping" function, NHE-3 may be involved in vectorial Na transport by the
      intestine.

PMID- 8282778
TI  - Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by
      pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees.
AB  - Knowledge of the pathogenetic mechanisms responsible for the activation of the
      coagulation system associated with endotoxemia is important for the development
      of improved modalities for prevention and treatment. We analyzed the appearance
      in plasma of TNF, IL-6, and indices of coagulation and fibrinolytic system
      activation in normal chimpanzees after intravenous infusion of endotoxin.
      Endotoxin infusion elicited reproducible and dose-dependent elevations in serum
      TNF and IL-6, as well as marked increases in thrombin generation in vivo as
      measured by immunoassays for prothrombin activation fragment F1 + 2, thrombin
      antithrombin III complexes, and fibrinopeptide A. Activation of the fibrinolytic
      mechanism was monitored with assays for plasminogen activator activity and
      plasmin-alpha 2-antiplasmin complexes. To potentially intervene in the molecular
      pathways elicited by endotoxin, pentoxifylline, an agent that interrupts
      "immediate early" gene activation by monocytes, or a potent monoclonal antibody
      that neutralizes tissue factor-mediated initiation of coagulation, were infused
      shortly before endotoxin. Pentoxifylline markedly inhibited increases in the
      levels of TNF and IL-6, as well as the effects on coagulation and fibrinolysis.
      In contrast, the monoclonal antibody to tissue factor completely abrogated the
      augmentation in thrombin generation, but had no effect on cytokine levels or
      fibrinolysis. We conclude that the endotoxin-induced activation of coagulation
      appears to be mediated by the tissue factor-dependent pathway, the fibrinolytic
      response triggered by endotoxin is not dependent on the generation of thrombin,
      and that the release of cytokines may be important in mediating the activation of
      both the coagulation and the fibrinolytic mechanisms in vivo.

PMID- 8282779
TI  - Duplication of 10 nucleotides in the erythroid band 3 (AE1) gene in a kindred
      with hereditary spherocytosis and band 3 protein deficiency (band 3PRAGUE).
AB  - We describe a duplication of 10 nucleotides (2,455-2,464) in the band 3 gene in a
      kindred with autosomal dominant hereditary spherocytosis and a partial deficiency
      of the band 3 protein that is reflected by decreased rate of transmembrane
      sulfate flux and decreased density of intramembrane particles. The mutant allele
      potentially encodes an abnormal band 3 protein with a 3.5-kD COOH-terminal
      truncation; however, we did not detect the mutant protein in the membrane of
      mature red blood cells. Since the mRNA levels for the mutant and normal alleles
      are similar and since the band 3 content is the same in the light and dense red
      cell fractions, we conclude that the mutant band 3 is either not inserted into
      the plasma membrane or lost from the membrane prior to the release of red blood
      cells into circulation. We further show that the decrease in band 3 content
      principally involves the dimeric laterally and rotationally mobile fraction of
      the band 3 protein, while the laterally immobile and rotationally restricted band
      3 fraction is left essentially intact. We propose that the decreased density of
      intramembrane particles decreases the stability of the membrane lipid bilayer and
      causes release of lipid microvesicles that leads to surface area deficiency and
      spherocytosis.

PMID- 8282780
TI  - Effect of nonprotective vaccination on antibody response to subsequent human
      immunodeficiency virus infection.
AB  - We have investigated the systemic anti-HIV antibody response in chimpanzees who
      were immunized with live vaccinia containing either the HIV envelope glycoprotein
      (gp160IIIB) or a control antigen (herpes simplex virus glycoprotein D) and then
      challenged with either a high dose (300,000 TCID50) or low dose (100 TCID50) of
      HIVIIIB. HIV was subsequently isolated from all animals, indicating failure of
      the vaccination to protect against HIV infection. Serum antibody responses were
      evaluated before immunization, at the time of challenge with HIV, and at multiple
      time points in the 9 mo after challenge. Immunization resulted in a more rapid
      rise of antibody to gp160 in both high and low dose animals. Antibodies to the V3
      loop induced upon infection were unaffected by immunization. In low dose animals,
      neutralizing antibody rose more rapidly and to higher levels in the immunized
      animals as compared with the control. There was no difference in neutralizing
      antibodies between immunized and control chimpanzees in the high dose group.
      Epitope mapping of the anti-gp 160 response indicated that immunization with
      gp160 vaccinia induced a postinfection antibody response to a region of gp41
      (amino acids 718-743) that was not immunogenic in control-vaccinated animals.
      These data indicate that failed vaccination with the HIV envelope can alter both
      the timing and epitope specificity of the subsequent anti-HIV antibody response.
      These studies also define the evolution and fine specificity of the antibody
      response during the critical period immediately postinfection.

PMID- 8282781
TI  - Analysis of regional hemodynamic regulation in response to scald injury.
AB  - Ultrasonic probes were placed around dog femoral arteries to record blood flow.
      Hind paw scalding with boiling water (5 s) caused a marked increase in
      ipsilateral femoral blood flow that persisted for the 2-h observation period.
      Contralateral femoral blood flow and systemic and pulmonary vascular resistances
      were unchanged. Compared to scald only animals, methysergide pretreatment
      diminished and shortened the femoral vasodilator response to scald (109 +/- 14 vs
      243 +/- 27 ml/min at 5 min; 59 +/- 14 vs 191 +/- 31 ml/min at 2 h). Pretreatment
      with ritanserin, BW A1433U83, atropine, ICI 118551, diphenhydramine, ranitidine,
      meclofenamate, L-nitro-arginine methyl ester, 3-amino-1,2,4-triazine, and U
      37883A had no effect on the increased femoral blood flow response to scald,
      suggesting this vasodilator response is not dependent upon activation of
      serotonergic2, adenosineA1, muscarinic, beta 2-adrenergic, histaminergic1 or
      histaminergic2 receptors, on cyclooxygenase products, endothelium-derived
      relaxing factor derived from nitric oxide (NO) synthase III, NO derived from NO
      synthase II, or KATP channels, respectively. Methysergide given after burn
      immediately reduced the augmented femoral blood flow to preburn levels,
      suggesting the vasodilator response to scald is mediated through continual
      activation of local serotonergic1-like receptors, which may be target site(s) for
      therapeutic interventions to influence burn-induced hemodynamic alterations.

PMID- 8282782
TI  - Prostaglandin E1 abrogates early reductive stress and zone-specific paradoxical
      oxidative injury in hypoperfused rat liver.
AB  - This study was designed to investigate the effects of prostaglandin E1 on
      reductive stress and the subsequent oxidative cell injury in hypoperfused rat
      liver. The intralobular heterogeneity of hepatocellular redox state,
      mitochondrial dysfunction, and intracellular hydroperoxide formation were
      visually monitored by digital microfluorography of pyridine nucleotide
      autofluorescence, rhodamine 123, and dichlorofluorescein fluorescence,
      respectively. Under the 25% low flow perfusion, pyridine nucleotide
      autofluorescence increased time-dependently and reached a steady state at 10 min
      among the entire lobules. The decrease in mitochondrial membrane potential was >
      20 mV in all portions of the lobules at 60 min. The onset of hydroperoxide
      formation was observed at 40 min in the marginally oxygenated proximal portion of
      anoxic pericentral regions and the oxidative impact reached a maximum level at 60
      min. Sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazo [1,5-a]-1,3,5
      triazine-4-olate monohydrate (BOF 4272), a novel xanthine oxidase inhibitor,
      suppressed the zone-specific oxidative changes without attenuating the increase
      in pyridine nucleotide autofluorescence and mitochondrial dysfunction.
      Pretreatment with prostaglandin E1 not only abrogated an early increase in
      pyridine nucleotide fluorescence and mitochondrial dysfunction induced by
      hypoperfusion but also diminished the subsequent midzonal oxidative injury. Since
      prostaglandin E1 has no oxyradical-scavenging action, the preventive effect of
      this reagent on the hypoxia-induced oxidative cell injury is attributable to the
      attenuation of mitochondrial dysfunction. These results suggest that, in low flow
      hypoxia, early reductive stress plays a key role in the initiation of xanthine
      oxidase-mediated midzonal oxidative changes, which may lead to subsequent
      centrilobular necrosis.

PMID- 8282783
TI  - Increased production of nitric oxide in coronary arteries during congestive heart
      failure.
AB  - Experiments were designed to determine whether a heterogeneity of endothelium
      dependent relaxations in arteries from different vascular beds exists in
      experimental congestive heart failure (CHF) and to determine the mediators of
      those responses. CHF was produced in dogs by rapid ventricular pacing for 15 d.
      Rings of coronary, femoral, and renal arteries with and without endothelium from
      control and CHF dogs were suspended in organ chambers for measurement of
      isometric force. In arteries contracted with prostaglandin F2 alpha, endothelium
      dependent relaxations to BHT 920 (an alpha 2-adrenergic agonist) were increased
      in coronary arteries from dogs with CHF (maximal relaxation: control -15 +/- 9%
      vs CHF -92 +/- 5%; n = 5-6; P < 0.05), with a modest enhancement in renal
      arteries. Relaxations to adenosine diphosphate and the calcium ionophore were
      unchanged. Relaxations to BHT 920 in CHF were reduced by NG monomethyl-L-arginine
      (L-NMMA) and pertussis toxin but not by indomethacin. These data suggest that
      endothelium-dependent relaxations are affected heterogeneously in CHF. The
      enhanced response to alpha 2-adrenergic agonists in the coronary artery is
      mediated by nitric oxide through a mechanism sensitive to inhibition by pertussis
      toxin. This selective increase in endothelium-dependent relaxations in the
      coronary artery may contribute to preserving coronary blood flow during CHF.

PMID- 8282784
TI  - Glanzmann thrombasthenia secondary to a Gly273-->Asp mutation adjacent to the
      first calcium-binding domain of platelet glycoprotein IIb.
AB  - We studied the defect responsible for Glanzmann thrombasthenia in a patient whose
      platelets expressed < 5% of the normal amount of GPIIb-IIIa. Genetic and
      biochemical evidence indicated that the patient's GPIIIa genes were normal.
      However, DNA analysis revealed the patient homozygous for a G818-->A substitution
      in her GPIIb genes, resulting in a Gly273-->Asp substitution adjacent to the
      first GPIIb calcium-binding domain. To determine how this mutation impaired GPIIb
      IIIa expression, recombinant GPIIb containing the mutation was coexpressed with
      GPIIIa in COS-1 cells. The GPIIb mutant formed stable GPIIb-IIIa heterodimers
      that were not immunoprecipitated by either of two heterodimer-specific monoclonal
      antibodies, indicating that the mutation disrupted the epitopes for these
      antibodies. Moreover, the GPIIb in the heterodimers was not cleaved into heavy
      and light chains, indicating that the heterodimers were not transported from the
      endoplasmic reticulum to the Golgi complex where GPIIb cleavage occurs, nor were
      the mutant heterodimers expressed on the cell surface. These studies demonstrate
      that a Gly273-->Asp mutation in GPIIb does not prevent the assembly of GPIIb-IIIa
      heterodimers, but alters the conformation of these heterodimers sufficiently to
      impair their intracellular transport. The impaired GPIIb-IIIa transport is
      responsible for the thrombasthenia in this patient.

PMID- 8282785
TI  - Gonadotropin stimulates ovarian renin-angiotensin system in the rabbit.
AB  - The present study was undertaken to assess the role of ovarian renin-angiotensin
      system (RAS) in the preovulatory cascade induced by gonadotropin exposure. In the
      in vitro perfused rabbit ovaries, exposure to human chorionic gonadotropin (hCG)
      enhanced the secretion rate of angiotensin II (Ang II) within 1 h. The secretion
      rate reached maximal levels at 6 h and then declined thereafter. The
      intrafollicular Ang II content and renin-like activity were also significantly
      increased at 2 and 4 h after exposure to hCG, compared with control ovaries
      perfused with medium alone. The level of intrafollicular Ang II after hCG
      exposure significantly exceeded the concentration of Ang II in an equivalent
      volume of plasma. The addition of 1 microM captopril to the perfusate
      significantly inhibited the secretion rate of Ang II stimulated by hCG; however,
      captopril affected neither the ovulatory efficiency nor prostaglandin production
      in ovaries treated with hCG. Captopril significantly inhibited the resumption of
      meiosis in the ovulated ova and follicular oocytes stimulated by hCG. The
      administration of 100 micrograms Ang II at 2-h intervals to the perfusate
      reversed the inhibitory effects of captopril on hCG-induced oocyte maturation. In
      conclusion, these data indicate that gonadotropin stimulates renin-like activity
      and Ang II production in the rabbit ovary. Ovarian renin-angiotensin system may
      play an important role in the process of oocyte maturation after exposure to
      gonadotropin.

PMID- 8282786
TI  - Platelet-activating factor causes ventilation-perfusion mismatch in humans.
AB  - We hypothesized that platelet-activating factor (PAF), a potent inflammatory
      mediator, could induce gas exchange abnormalities in normal humans. To this end,
      the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation
      perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory
      system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1
      [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared
      to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF
      induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a
      rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and
      resistance of the respiratory system (P < 0.01), and decreased systemic arterial
      pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall
      (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial
      alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF,
      because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of
      ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04),
      respectively. We conclude that in normal subjects, inhaled PAF results in
      considerable immediate VA/Q inequality and gas exchange impairment. These results
      reinforce the notion that PAF may play a major role as a mediator of inflammation
      in the human lung.

PMID- 8282787
TI  - Lovastatin increases arachidonic acid levels and stimulates thromboxane synthesis
      in human liver and monocytic cell lines.
AB  - The effect of lovastatin (LOV), the inhibitor of 3-hydroxy-3-methyl-glutaryl
      coenzyme A reductase, on linoleic acid (LA, 18:2n-6) metabolism was examined in
      human monocytic Mono Mac 6 (MM6) and hepatoma Hep G2 cells. The desaturation of
      LA was examined after LOV (72 h, 10 microM) or dimethylsulfoxide (LOV carrier, <
      0.1%) and [14C]LA (last 18 h, 0.3 microCi, 5 microM). In both cell lines, LOV
      reduced the percentage of 14C label associated with LA and increased the
      percentage of label in the 20:4n-6 and the 22:5n-6 fractions. In Hep G2 but not
      MM6 cells, this effect was fully reversible by means of coincubation with
      mevalonic acid (500 microM), but not with cholesterol or lipoproteins. In both
      cell lines, the LOV-mediated increase in LA desaturation resulted in dose
      dependent reductions of LA and elevations of AA in cellular phospholipids. The
      lipids secreted by LOV-treated Hep G2 cells were also enriched in arachidonic
      acid (AA). In the MM6 cells, LOV increased release of thromboxane upon
      stimulation with the calcium ionophore A23187. In summary, our findings of higher
      LA desaturation and AA enrichment of lipids secreted by the Hep G2 cells suggest
      that LOV treatment may increase the delivery of AA from the liver to extrahepatic
      tissues. The changes in membrane fatty acid composition can influence a variety
      of cellular functions, such as eicosanoid synthesis in monocytic cells. The
      mechanism appears to be related to the reduced availability of intermediates of
      cholesterogenesis.

PMID- 8282788
TI  - The devil's in the details: progress in familial hypertrophic cardiomyopathy.

PMID- 8282789
TI  - Thrombus formation and platelet-vessel wall interaction in the nephrotic syndrome
      under flow conditions.
AB  - Increased in vitro platelet aggregability and hypercoagulability are generally
      held to be main determinants in the prethrombotic state in nephrosis. In vivo,
      however, thrombotic events depend on the dynamic interaction of flowing blood
      with the vessel wall. The present study confirms that aggregability of platelets
      of nephrotic patients is significantly increased by mere stirring or by exogenous
      stimuli as adenosine diphosphate and arachidonic acid. Moreover, the nephrotic
      patients have high von Willebrand factor and decreased red blood cell
      deformability, which normally increase platelet-vessel wall interaction. However,
      perfusion studies under well-defined flow conditions, in which anticoagulated
      nephrotic blood was exposed to deendothelialized human umbilical artery segments
      and sprayed collagen, showed normal platelet adhesion and only a modest increase
      in the deposition of platelet aggregates. This suggests that some factor
      counteracts platelet-vessel wall interaction under flow conditions in the
      nephrotic syndrome. When tissue factor associated with endothelial extracellular
      matrix (ECM) was allowed to generate thrombin, perfusions with nephrotic blood
      over this ECM resulted in a strong increase in fibrin generation. The capacity of
      patient blood to form increased amounts of fibrin appeared strongly correlated
      with the level of hyperfibrinogenemia. Platelet adhesion as well as aggregation
      in these experiments was even decreased below control values. This suggests that
      fibrin coverage may block the direct contact between blood platelets and matrix.
      We therefore also studied the isolated effect of high fibrinogen on platelet
      vessel wall interaction by increasing fibrinogen concentrations in normal blood.
      Modulation of fibrinogen concentrations in normal blood could mimic all the
      observations in nephrotic blood: platelet aggregation in suspension increased
      with increasing concentrations of fibrinogen, while platelet adhesion and
      aggregate formation under flow conditions decreased. In perfusions over tissue
      factor-rich matrix, fibrin deposition increased. Therefore, our observations
      indicate that nephrotic hyperaggregability in suspension is not associated with
      increased platelet vessel wall-interaction under flow conditions. The latter is
      probably counteracted by high levels of fibrinogen. Our observations further
      suggest that hyperfibrinogenemia may be a major thrombotic risk factor in
      nephrosis by inducing more fibrin depositions.

PMID- 8282790
TI  - Transport of sodium and urea in outer medullary descending vasa recta.
AB  - We dissected and perfused outer medullary vasa recta (OMVR) from vascular bundles
      in the rat. Permeabilities of sodium (PNa) and urea (Pu) were simultaneously
      determined from the lumen-to-bath efflux of 22Na and [14C]urea. PNa and Pu were
      also measured by in vivo microperfusion of descending (DVR) and ascending vasa
      recta (AVR) at the papillary tip of Munich-Wistar rats. In some OMVR PNa was
      indistinguishable from zero. The mean +/- SE of PNa (x 10(-5), cm/s) in OMVR was
      76 +/- 9. Pu in OMVR was always very high (x 10(-5), cm/s), 360 +/- 14. There was
      no correlation between OMVR PNa and Pu. Inner medullary AVR and DVR had PNa of
      115 +/- 10 and 75 +/- 10, respectively, and Pu of 121 +/- 10 and 76 +/- 11,
      respectively. PNa and Pu in papillary vasa recta were always nearly identical and
      highly correlated. Transport of [14C] urea in OMVR was reversibly inhibited by
      addition of unlabeled urea or phloretin to the bath and lumen, providing evidence
      for carrier-mediated transport. These data suggest that sodium and urea might
      traverse the wall of inner medullary vasa recta by a paracellular pathway while
      urea also crosses by a transcellular route in OMVR. Electron microscopic
      examination of seven in vitro perfused OMVR revealed no fenestrations and
      exposure of these vessels to 10 microM calcium ionophore A23187 or 1 nM
      angiotensin II resulted in reversible contraction, suggesting that in vitro
      perfused OMVR are DVR only.

PMID- 8282791
TI  - Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a
      family with analphalipoproteinemia.
AB  - We report a Canadian kindred with a novel mutation in the apolipoprotein (apo) A
      I gene causing analphalipoproteinemia. The 34-yr-old proband, product of a
      consanguineous marriage, had bilateral retinopathy, bilateral cataracts,
      spinocerebellar ataxia, and tendon xanthomata. High density lipoprotein
      cholesterol (HDL-C) was < 0.1 mM and apoA-I was undetectable. Genomic DNA
      sequencing of the proband's apoA-I gene identified a nonsense mutation at codon [
      2], which we designate as Q[-2]X. This mutation causes a loss of endonuclease
      digestion sites for both BbvI and Fnu4HI. Genotyping identified four additional
      homozygotes, four heterozygotes, and two unaffected subjects among the first
      degree relatives. Q[-2]X homozygosity causes a selective failure to produce any
      portion of mature apoA-I, resulting in very low plasma level of HDL.
      Heterozygosity results in approximately half-normal apoA-I and HDL. Gradient gel
      electrophoresis and differential electroimmunodiffusion assay revealed that the
      HDL particles of the homozygotes had peak Stokes diameter of 7.9 nm and contained
      apoA-II without apoA-I (Lp-AII). Heterozygotes had an additional fraction of HDL3
      like particles. Two of the proband's affected sisters had documented premature
      coronary heart disease. This kindred, the third reported apoA-I gene mutation
      causing isolated complete apoA-I deficiency, appears to be at significantly
      increased risk for atherosclerosis.

PMID- 8282792
TI  - Hepatitis B virus persistence after recovery from acute viral hepatitis.
AB  - Contrary to current opinion, the disappearance of hepatitis B surface antigen
      (HBsAg) from the serum, the development of anti-HBs antibodies, and normalization
      of liver function may not reflect complete virological recovery from acute
      hepatitis B virus (HBV) infection. By using the polymerase chain reaction (PCR),
      in the current study we demonstrate long-term persistence of HBV DNA in the serum
      and peripheral blood mononuclear cells (PBMC) of four patients for up to 70 mo
      after complete clinical, biochemical, and serological recovery from acute viral
      hepatitis. Serum HBV DNA reactivity co-sedimented with HBsAg in sucrose
      gradients, and it displayed the size and density characteristics of naked core
      particles and intact HBV virions, presumably contained within circulating immune
      complexes in these anti-HBs antibody-positive sera. HBV DNA was also present in
      PBMC in late convalescent samples from all four patients, and HBV RNA was
      detected in late convalescent phase PBMC in two of these patients. These results
      suggest that HBV DNA, and possibly HBV virions, can be present in the serum, and
      that the viral genome can persist in a transcriptionally active form in PBMC for
      > 5 yr after complete clinical and serological recovery from acute viral
      hepatitis.

PMID- 8282793
TI  - Lactate release from the subcutaneous tissue in lean and obese men.
AB  - Lactate concentration in the subcutaneous interstitial fluid and adipose tissue
      blood flow (ATBF, ml/100 g.min) were simultaneously measured with the
      microdialysis technique combined with 133Xe clearance in the abdominal and
      femoral subcutaneous adipose tissue in nine lean and nine obese men. The studies
      were performed both in the postabsorptive state and 2 h after an oral glucose
      load and the results compared to the lactate levels in arterialized venous
      plasma. After an overnight's fast, arterial lactate was 738 +/- 49 and 894 +/- 69
      microM (mean +/- SE) (P < 0.05) in the lean and obese subjects, respectively. The
      interstitial lactate levels were significantly higher than blood lactate in both
      subject groups without any regional differences. Abdominal and femoral ATBF was
      3.2 +/- 0.6 vs. 2.8 +/- 0.4 and 1.7 +/- 0.3 vs. 2.4 +/- 0.4 ml/100 g.min (P <
      0.05) in lean and obese subjects, respectively. Mean apparent lactate release
      from the abdominal vs. femoral adipose tissue in the fasting state was 10.5 +/-
      3.1 vs. 8.6 +/- 2.3 and 6.0 +/- 2.3 vs. 8.5 +/- 2.3 mumol/kg.min (NS) in lean and
      obese subjects, respectively. Both plasma and interstitial lactate levels
      increased significantly after an oral glucose load in both subject groups.
      However, apparent lactate release increased significantly only in the lean group.
      It is concluded that subcutaneous adipose tissue is a significant source of whole
      body lactate release in the postabsorptive state and that this is further
      enhanced in obese subjects due to their large adipose mass.

PMID- 8282794
TI  - Linkage of azurophil granule secretion in neutrophils to chloride ion transport
      and endosomal transcytosis.
AB  - Neutrophils contain at least two types of secretory granules. The present work
      links the secretion of the (lysosomal type) azurophil granules, but not that of
      specific granules, to endosomal transport mechanisms. (a) Selective stimulation
      of azurophil granule secretion by the Na-ionophore Monensin, or nonselective
      stimulation by FMLP after cytochalasin B pretreatment elicited marked pinocytic
      activity in parallel with azurophil granule release, whereas FMLP alone,
      selective for specific granules, elicited little fluid pinocytosis. (b) Pinosomes
      thus formed fused with azurophil granules, suggesting that exocytosis of
      azurophil granules might occur via endosomal organelles. This hypothesis was
      tested by determining the effect on the endosomal pathway(s) of two treatments
      that selectively prevent the release of azurophil granule contents without
      interfering with specific granule secretion, namely replacement of Cl- with
      gluconate- or the addition of zinc. Replacement of Cl- was found to impair the
      pinocytosis process itself, whereas ZnSO4 appeared to prevent the fusion between
      endosomes and azurophil granules. These data support the concept that the
      (lysosomal type) azurophil granules, but not the specific granules, are secreted
      through the endosomal pathway.

PMID- 8282795
TI  - Hypoxic and ischemic hypoxia exacerbate brain injury associated with metabolic
      encephalopathy in laboratory animals.
AB  - Hypoxemia is a major comorbid factor for permanent brain damage in several
      metabolic encephalopathies. To determine whether hypoxia impairs brain adaptation
      to hyponatremia, worsening brain edema, we performed in vitro and in vivo studies
      in cats and rats with hyponatremia plus either ischemic or hypoxic hypoxia.
      Mortality with hypoxic hypoxia was 0%; with hyponatremia, 22%; and with
      hyponatremia+hypoxia, 100%. Hyponatremia in cats produced brain edema, with a
      compensatory decrease of brain sodium. Ischemic hypoxia also resulted in brain
      edema, but with elevation of brain sodium. However, when ischemic hypoxia was
      superimposed upon hyponatremia, there was elevation of brain sodium with further
      elevation of water. Outward sodium transport in cat cerebral cortex synaptosomes
      was measured via three major pathways through which brain osmolality can be
      decreased. After hyponatremia, sodium transport was significantly altered such
      that brain cell osmolality would decrease: 44% increase in Na(+)-K(+)-ATPase
      transport activity (ouabain inhibitable); 26% decrease in amiloride-sensitive
      sodium uptake. The change in veratridine-stimulated sodium uptake was not
      significant (P > 0.05). When ischemic hypoxia was superimposed upon hyponatremia,
      all of the cerebral adaptive changes induced by hyponatremia alone were
      eliminated. Thus, hypoxia combined with hyponatremia produces a major increase in
      brain edema and mortality, probably by eliminating the compensatory mechanisms of
      sodium transport initiated by hyponatremia that tend to minimize brain swelling.

PMID- 8282796
TI  - Novel Pseudomonas product stimulates interleukin-8 production in airway
      epithelial cells in vitro.
AB  - Because high concentrations of IL-8 are found in the sputum of cystic fibrosis
      patients, we hypothesized that Pseudomonas aeruginosa (PA) induces the production
      of IL-8 in airway epithelial cells and in monocytes. Therefore, we incubated the
      supernatant from PA culture with human transformed bronchial epithelial cells (16
      HBE) or with monocytes. The culture medium of 16-HBE cells that had been
      incubated with PA supernatant for 6 h had chemotactic activity that was inhibited
      by an antibody to human IL-8. The PA supernatant induced IL-8 production by
      primary bronchial epithelial cells, by 16-HBE cells, and by monocytes. After
      incubation with PA supernatant, 16-HBE cells showed a marked increase in the
      levels of IL-8 gene expression. The PA product responsible for IL-8 production
      resisted freezing, boiling, and proteolysis. This product was not lipid
      extractable and was present in a 1-kD filtrate. We conclude that a small
      molecular mass product of PA stimulates IL-8 production by 16-HBE cells and by
      monocytes, and that the chemotactic activity produced by 16-HBE cells after
      exposure to PA is due principally to IL-8.

PMID- 8282797
TI  - Effects of cigarette smoking and its cessation on lipid metabolism and energy
      expenditure in heavy smokers.
AB  - The relationship between thermogenic and potentially atherogenic effects of
      cigarette smoking (CS) and its cessation was investigated. Heavy smokers (n = 7,
      serum cotinine > 200 ng/ml, > 20 cigarettes/d) were maintained on isoenergetic,
      constant diets for 2 wk, 1 wk with and 1 wk without CS. Stable isotope infusions
      with indirect calorimetry were performed on day 7 of each phase, after an
      overnight fast. CS after overnight abstention increased resting energy
      expenditure by 5% (not significant vs. non-CS phase; P = 0.18). CS increased the
      flux of FFA by 77%, flux of glycerol by 82%, and serum FFA concentrations by 73%
      (P < 0.02 for each), but did not significantly affect fat oxidation. Hepatic
      reesterification of FFA increased more than threefold (P < 0.03) and adipocyte
      recycling increased nonsignificantly (P = 0.10). CS-induced lipid substrate
      cycles represented only 15% (estimated 11 kcal/d) of observed changes in energy
      expenditure. De novo hepatic lipogenesis was low (< 1-2 g/d) and unaffected by
      either acute CS or its chronic cessation. Hepatic glucose production was not
      affected by CS, despite increased serum glycerol and FFA fluxes. Cessation of CS
      caused no rebound effects on basal metabolic fluxes. In conclusion, a metabolic
      mechanism for the atherogenic effects of CS on serum lipids (increased hepatic
      reesterification of FFA) has been documented. Increased entry of FFA accounts for
      CS-induced increases in serum FFA concentrations. The thermogenic effect of CS is
      small or absent in heavy smokers while the potentially atherogenic effect is
      maintained, and cessation of CS does not induce a rebound lipogenic milieu that
      specifically favors accrual of body fat in the absence of increased food intake.

PMID- 8282798
TI  - Prognostic implications of novel beta cardiac myosin heavy chain gene mutations
      that cause familial hypertrophic cardiomyopathy.
AB  - Three novel beta cardiac myosin heavy chain (MHC) gene missense mutations,
      Phe513Cys, Gly716Arg, and Arg719Trp, which cause familial hypertrophic
      cardiomyopathy (FHC) are described. One mutation in exon 15 (Phe513Cys) does not
      alter the charge of the encoded amino acid, and affected family members have a
      near normal life expectancy. The Gly716Arg mutation (exon 19; charge change of
      +1) causes FHC in three family members, one of whom underwent transplantation for
      heart failure. The Arg719Trp mutation (exon 19; charge change of -1) was found in
      four unrelated FHC families with a high incidence of premature death and an
      average life expectancy in affected individuals of 38 yr. A comparable high
      frequency of disease-related deaths in four families with the Arg719Trp mutation
      suggests that this specific gene defect directly accounts for the observed
      malignant phenotype. Further, the significantly different life expectancies
      associated with the Arg719Trp vs. Phe513Cys mutation (P < 0.001) support the
      hypothesis that mutations which alter the charge of the encoded amino acid affect
      survival more significantly than those that produce a conservative amino acid
      change.

PMID- 8282799
TI  - Short-term effects of uninephrectomy on electrical properties of the cortical
      collecting duct from rabbit remnant kidneys.
AB  - Microelectrode techniques were used to assess the electrical properties of the
      collecting duct cell in the isolated perfused cortical collecting duct from
      remnant kidneys 3, 6, and 24 h after uninephrectomy (UNX); results were compared
      with those from sham-operated kidneys. Plasma aldosterone levels did not change
      during the time course after UNX. The lumen-negative transepithelial voltage was
      elevated significantly 3 h after UNX, and was increased further 24 h after UNX.
      The basolateral membrane voltage (VB) was elevated 6 h after UNX, and then was
      increased further at 24 h. Although the tight junction conductance and the
      fractional apical membrane resistance (fRA) were not altered at any time points
      after UNX, the apical membrane conductance as well as the transepithelial (GT)
      and basolateral membrane conductances increased 6 and 24 h after UNX. The changes
      in apical membrane voltage, GT, and fRA upon addition of luminal amiloride
      increased just 3 h after UNX, and then remained elevated at 6 and 24 h. The
      changes in apical membrane voltage and GT upon addition of luminal Ba2+, the
      changes in VB upon addition of bath ouabain, and the changes in VB, GT, and fRA
      upon raising bath K+ were not influenced 3 h after UNX, but increased at 6 and 24
      h. At these latter periods after UNX, the transference number of Cl- of the
      basolateral membrane decreased significantly, whereas the transference number of
      K+ of the basolateral membrane increased significantly. Simultaneously, addition
      of Ba2+ to the bath caused the VB to hyperpolarize in parallel with decreases in
      GT and fRA. We conclude: (a) the initial effect of UNX (3 h) in the collecting
      duct cell is an increase in apical membrane Na+ conductance; (b) the delayed
      effects of UNX (6 and 24 h) are increases in apical membrane K+ conductance as
      well as basolateral membrane Na(+)-K+ pump activity and K+ conductance; (c) the
      hyperpolarization of VB at 6 and 24 h after UNX may result in the decrease of the
      ratio of the relative Cl- conductance to the relative K+ conductance of the
      basolateral membrane and also may increase passive K+ entry into the cell across
      the basolateral membrane; (d) these time-dependent electrical changes occur
      independently of plasma aldosterone levels.

PMID- 8282800
TI  - Vulnerability of the human airway epithelium to hyperoxia. Constitutive
      expression of the catalase gene in human bronchial epithelial cells despite
      oxidant stress.
AB  - Although catalase is a major intracellular antioxidant, the expression of the
      human catalase gene appears to be limited in the airway epithelium, making these
      cells vulnerable to oxidant stress. The basis for this limited gene expression
      was examined by evaluation of the expression of the endogenous gene in human
      bronchial epithelial cells in response to hyperoxia. Hyperoxia failed to
      upregulate endogenous catalase gene expression, in contrast to a marked increase
      in expression of the heat shock protein gene. Sequence analysis of 1.7 kb of the
      5'-flanking region of the human catalase gene showed features of a "house
      keeping" gene (no TATA box, high GC content, multiple CCAAT boxes, and
      transcription start sites). Transfection of human bronchial epithelial cells with
      fusion genes composed of various lengths of the catalase 5'-flanking region and
      luciferase as a reporter gene showed low level constitutive promoter activity
      that did not change after exposure to hyperoxia. Importantly, using a replication
      deficient recombinant adenoviral vector containing the human catalase cDNA,
      levels of catalase were significantly increased in human airway epithelial cells
      and this was associated with increased survival of the cells when exposed to
      hyperoxia. These observations provide a basis for understanding the sensitivity
      of the human airway epithelium to oxidant stress and a strategy for protecting
      the epithelium from such injury.

PMID- 8282801
TI  - A unique property of a plasma proteoglycan, the C1q inhibitor. An anticoagulant
      state resulting from its binding to fibrinogen.
AB  - The C1q inhibitor, C1qI, an approximately 30-kD circulating chondroitin-4 sulfate
      proteoglycan, displayed concentration-dependent prolongation of plasma and
      fibrinogen solution clotting times. Under factor XIIIa catalyzed cross-linking
      conditions and maximum C1qI concentrations, minor amounts of clot formed
      displaying complete gamma-gamma dimer formation but virtually no alpha-polymer
      formation. The anticoagulant effect was undiminished by its binding to C1q, by
      increased ionic strength, and by CaCl2, but was abolished by incubation of C1qI
      with chondroitinase ABC. 125I-labeled C1qI bound to immobilized fibrinogen,
      fibrin monomer, fibrinogen plasmic fragments D1 and E, and fibrin polymers.
      Occupancy on the E domain required uncleaved fibrinopeptides together with
      another structure(s), and it did not decrease binding of thrombin to fibrinogen.
      Occupancy on the D domain did not decrease the fibrinogen binding to fibrin
      monomer. We conclude that the E domain occupancy impaired fibrinopeptide
      cleavage, and occupancy on the D domain impaired polymerization, both steric
      hindrance effects. C1qI binding to fibrinogen explains at least in part the well
      known fibrin(ogen) presence in immune complex-related lesions, and the fibrinogen
      presence in vascular basement membranes and atheromata. We postulate that fibrin
      binding by resident basement membrane proteoglycans provides dense anchoring of
      thrombus, substantially enhancing its hemostatic function.

PMID- 8282802
TI  - Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density
      lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase
      deficiency and fish-eye disease.
AB  - Classic (complete) lecithin:cholesterol acyltransferase (LCAT) deficiency and
      Fish-eye disease (partial LCAT deficiency) are genetic syndromes associated with
      markedly decreased plasma levels of high density lipoprotein (HDL) cholesterol
      but not with an increased risk of atherosclerotic cardiovascular disease. We
      investigated the metabolism of the HDL apolipoproteins (apo) apoA-I and apoA-II
      in a total of five patients with LCAT deficiency, one with classic LCAT
      deficiency and four with Fish-eye disease. Plasma levels of apoA-II were
      decreased to a proportionately greater extent (23% of normal) than apoA-I (30% of
      normal). In addition, plasma concentrations of HDL particles containing both apoA
      I and apoA-II (LpA-I:A-II) were much lower (18% of normal) than those of
      particles containing only apoA-I (LpA-I) (51% of normal). The metabolic basis for
      the low levels of apoA-II and LpA-I:A-II was investigated in all five patients
      using both exogenous radiotracer and endogenous stable isotope labeling
      techniques. The mean plasma residence time of apoA-I was decreased at 2.08 +/-
      0.27 d (controls 4.74 +/- 0.65 days); however, the residence time of apoA-II was
      even shorter at 1.66 +/- 0.24 d (controls 5.25 +/- 0.61 d). In addition, the
      catabolism of apoA-I in LpA-I:A-II was substantially faster than that of apoA-I
      in LpA-I. In summary, genetic syndromes of either complete or partial LCAT
      deficiency result in low levels of HDL through preferential hypercatabolism of
      apoA-II and HDL particles containing apoA-II. Because LpA-I has been proposed to
      be more protective than LpA-I:A-II against atherosclerosis, this selective effect
      on the metabolism of LpA-I:A-II may provide a potential explanation why patients
      with classic LCAT deficiency and Fish-eye disease are not at increased risk for
      premature atherosclerosis despite markedly decreased levels of HDL cholesterol
      and apoA-I.

PMID- 8282803
TI  - Steroid-resistant asthma. Cellular mechanisms contributing to inadequate response
      to glucocorticoid therapy.
AB  - The current study examined whether alterations in glucocorticoid receptor (GR)
      binding contribute to poor response to glucocorticoid therapy in asthma. 29
      asthma patients with forced expiratory volume in 1 s (FEV1) < 70% predicted were
      studied. Patients were classified as steroid sensitive (SS) if their morning FEV1
      increased > 30% after a 1-wk course of oral prednisone 20 mg twice daily and
      steroid resistant (SR) if they failed to increase > 15%. PBMC obtained from these
      two groups, 17 SR and 12 SS, as well as 12 normal controls were analyzed. SR
      patients had two distinguishable GR binding abnormalities: 15 of the 17 SR
      patients demonstrated a significantly reduced GR binding affinity, as compared
      with SS patients (P = 0.0001) and normal controls (P = 0.0001). This defect was
      localized to T cells and reverted to normal after 48 h in culture media. However,
      incubation with a combination of IL-2 and IL-4 sustained this abnormality. The
      other two SR patients had an abnormally low GR number with normal binding
      affinity that was not limited to T cells. Furthermore, GR number failed to
      normalize after incubation in media alone or IL-2 and IL-4. Therefore, SR asthma
      may be due to more than one abnormality, the majority related to a reversible
      cytokine-induced reduction in GR binding affinity and the second related to an
      irreversible reduction in GR number. These findings may have important
      implications for the design of alternative treatment approaches for recalcitrant
      asthma.

PMID- 8282804
TI  - Protective role of intracellular superoxide dismutase against extracellular
      oxidants in cultured rat gastric cells.
AB  - We examined the role of intracellular superoxide dismutase (SOD) as an
      antioxidant by studying the effect of diethyldithiocarbamate (DDC) on
      extracellular H2O2-induced damage in cultured rat gastric mucosal cells. 51Cr
      labeled monolayers from rat stomachs were exposed to glucose oxidase-generated
      H2O2 or reagent H2O2, which both caused a dose-dependent increase in 51Cr
      release. DDC dose-dependently enhanced 51Cr release by hydrogen peroxide,
      corresponding with inhibition of endogenous SOD activity. This inhibition was not
      associated either with modulation of other antioxidant defenses, or with
      potentiation of injury by nonoxidant toxic agents. Enhanced hydrogen peroxide
      damage by DDC was significantly prevented by chelating cellular iron with
      deferoxamine or phenanthroline. Inhibition of cellular xanthine oxidase (possible
      source of superoxide production) by oxypurinol neither prevented lysis by
      hydrogen peroxide nor diminished DDC-induced sensitization to H2O2. We conclude
      that (a) extracellular H2O2 induces dose dependent damage to cultured gastric
      mucosal cells; (b) intracellular SOD plays an important role in preventing H2O2
      damage; (c) generation of superoxide seems to occur intracellularly after
      exposure to H2O2, but independent of cellular xanthine oxidase; and (d) cellular
      iron mediates the damage by catalyzing the production of more reactive species
      from superoxide and H2O2, the process which causes ultimate cell injury.

PMID- 8282805
TI  - Induction of angiotensin converting enzyme in the neointima after vascular
      injury. Possible role in restenosis.
AB  - Angiotensin II (Ang II) promotes growth of vascular smooth muscle cells in vitro.
      Consistent with this, Ang II enhances neointimal proliferation in vivo after
      vascular injury, while angiotensin converting enzyme (ACE) inhibitors attenuate
      this process. Since tissue ACE plays a key role in the control of local Ang II
      production, we examined whether vascular injury resulted in an increase in
      vascular ACE expression that may result in increased Ang II production. Abdominal
      aorta of Sprague-Dawley rats were injured with a 2 French balloon catheter.
      Morphometrical changes, ACE enzymatic activity, and localization of ACE by
      immunohistochemistry in injured and uninjured aorta were analyzed. Vascular ACE
      activity in the injured aorta was significantly higher than in the uninjured
      aorta, while serum and lung ACE levels were not different between the two groups.
      The cellular distribution of the ACE protein in the neointima was similar to that
      of alpha smooth muscle actin but differed from those of endothelial (von
      Willebrand factor) or monocytes/macrophages (ED-1) markers, demonstrating that
      ACE was expressed in neointimal smooth muscle cells. These data demonstrate that
      vascular injury results in the induction of vascular ACE and suggest that the
      inhibition of vascular ACE may be important in the prevention of restenosis after
      balloon injury.

PMID- 8282806
TI  - H19, a developmentally regulated gene, is reexpressed in rat vascular smooth
      muscle cells after injury.
AB  - Vascular smooth muscle cell migration, proliferation, and differentiation are
      central to blood vessel development. Since neointimal formation after vascular
      injury may require the reexpression of a smooth muscle developmental sequence, we
      examined the expression of H19, a developmentally regulated gene, in rat blood
      vessels. Expression of the H19 gene is associated with the differentiation
      process that takes place during development of many tissues. Consistent with
      this, H19 was highly expressed in the 1-d-old rat aorta but was undetectable in
      the adult. H19 transcripts were only minimally detected in uninjured carotid
      artery but were abundant at 7 and 14 d after injury and were localized by in situ
      hybridization, primarily to the neointima. H19 transcript were undetectable in
      proliferating neointimal cells in culture but became highly abundant in
      postconfluent, differentiated neointimal cells. H19 transcripts were only
      minimally expressed in adult medial smooth muscle cells grown under the identical
      conditions. Thus, H19 may play an important role in the normal development and
      differentiation of the blood vessel and in the phenotypic changes of the smooth
      muscle cells, which are associated with neointimal lesion formation. The vascular
      injury model may be a useful system to use in examining the function of H19.

PMID- 8282807
TI  - Evidence of antigen receptor-influenced oligoclonal B lymphocyte expansion in the
      synovium of a patient with longstanding rheumatoid arthritis.
AB  - Plasma cell infiltration of synovium is common in longstanding rheumatoid
      arthritis (RA). The mechanism(s) underlying synovial B cell proliferation remains
      unclear. One theory invokes nonspecific polyclonal stimuli; another implicates
      antigen as the driving force. Antigen-driven repertoires are characteristically
      enriched for related sets of V gene segments containing similar sequence in the
      antigen binding site (complementarity-determining regions; CDRs). To study the
      forces shaping B cell proliferation, we analyzed V kappa transcripts expressed in
      the synovium of an RA patient. We found Humkv325, a developmentally regulated V
      kappa III gene segment associated with autoantibody reactivity, in > 10% of
      randomly-chosen synovial C kappa cDNAs. Two sets of sequences contained identical
      charged amino acid residues at the V kappa-J kappa join, apparently due to N
      region addition. We generated "signature" oligonucleotides from these CDR3s and
      probed PCR amplified V kappa products from the synovium and PBLs of the same
      patient, and from PBLs and spleen of individuals without rheumatic disease.
      Significant expression of transcripts containing these unique CDR3 sequences
      occurred only in the patient's synovium. Thus, in this synovium there is
      expansion of a limited set of B cell clones expressing antigen receptors that
      bear evidence of antigen selection.

PMID- 8282808
TI  - Persistence of multiple maternal genotypes of human immunodeficiency virus type I
      in infants infected by vertical transmission.
AB  - The extent of nucleotide variation within the HIV-1 env hypervariable domains
      serves as a marker of virus genotypes within infected individuals and as a means
      to track transmission of the virus between individuals. We analyzed env V1 and V2
      sequences in longitudinal samples from two HIV-1-infected mothers, each with
      three children infected by maternal transmission of the virus. Sequences in
      samples that were obtained from two infants at 2 d and 4 wk after birth displayed
      more variation in V1 and V2 than maternal samples obtained at the same times.
      Multiple HIV-1 genotypes were identified in each mother. In each family, multiple
      maternal HIV-1 genotypes were transmitted to the infants. Specific amino acid
      residues in the hypervariable domains were conserved within sequences from each
      family producing a family-specific amino acid signature pattern in V1 and V2.
      Viruses that were highly related to maternal viruses in signature pattern
      persisted for as long as 4 yr in the older children. Results support a model of
      transmission involving multiple HIV-1 genotypes with development of genetic
      variation from differential outgrowth and accumulation of genetic changes within
      each individual.

PMID- 8282809
TI  - Lipopolysaccharide induces prostaglandin H synthase-2 protein and mRNA in human
      alveolar macrophages and blood monocytes.
AB  - We and others have previously demonstrated that human alveolar macrophages
      produce more PGE2 in response to lipopolysaccharide (LPS) than do blood
      monocytes. We hypothesized that this observation was due to a greater increase in
      prostaglandin H synthase-2 (PGHS-2) enzyme mass in the macrophage compared to the
      monocyte. To evaluate this hypothesis, alveolar macrophages and blood monocytes
      were obtained from healthy nonsmoking volunteers. The cells were cultured in the
      presence of 0 to 10 micrograms/ml LPS. LPS induced the synthesis of large amounts
      of a new 75-kD protein in human alveolar macrophages, and a lesser amount in
      monocytes. Synthesis of this protein required more than 6 h and peaked in 24 to
      48 h; the protein reacted with an anti-PGHS-2 antibody prepared against mouse
      PGHS-2. Associated with synthesis of the protein was a marked increase in LPS
      stimulated and arachidonic acid-stimulated synthesis of PGE2 by alveolar
      macrophages compared to monocytes. Cells not exposed to LPS contained only PGHS-1
      and synthesized very little PGE2 during culture or in response to exogenous
      arachidonic acid. An LPS-induced mRNA, which hybridized to a human cDNA probe for
      PGHS-2 mRNA, was produced in parallel with production of this new protein and was
      produced in much greater amounts by alveolar macrophages compared to blood
      monocytes. This mRNA was not detectable in cells not exposed to LPS. In contrast,
      both types of cells contain mRNA, which hybridizes to a cDNA probe for PGHS-1.
      This mRNA did not increase in response to LPS. LPS also had no effect on PGHS-1
      protein. These data demonstrate that PGE2 synthesis in human alveolar macrophages
      and blood monocytes correlates to the mass of PGHS-2 in the cell. We conclude
      that the greater ability of the macrophage to synthesize PGE2 in response to LPS
      is due to greater synthesis of PGHS-2 by the macrophage.

PMID- 8282810
TI  - The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the
      major renal reabsorptive mechanism for D-glucose.
AB  - The major reabsorptive mechanism for D-glucose in the kidney is known to involve
      a low affinity high capacity Na+/glucose cotransporter, which is located in the
      early proximal convoluted tubule segment S1, and which has a Na+ to glucose
      coupling ratio of 1:1. Here we provide the first molecular evidence for this
      renal D-glucose reabsorptive mechanism. We report the characterization of a
      previously cloned human kidney cDNA that codes for a protein with 59% identity to
      the high affinity Na+/glucose cotransporter (SGLT1). Using expression studies
      with Xenopus laevis oocytes we demonstrate that this protein (termed SGLT2)
      mediates saturable Na(+)-dependent and phlorizin-sensitive transport of D-glucose
      and alpha-methyl-D-glucopyranoside (alpha MeGlc) with Km values of 1.6 mM for
      alpha MeGlc and approximately 250 to 300 mM for Na+, consistent with low affinity
      Na+/glucose cotransport. In contrast to SGLT1, SGLT2 does not transport D
      galactose. By comparing the initial rate of [14C]-alpha MeGlc uptake with the
      Na(+)-influx calculated from alpha MeGlc-evoked inward currents, we show that the
      Na+ to glucose coupling ratio of SGLT2 is 1:1. Using combined in situ
      hybridization and immunocytochemistry with tubule segment specific marker
      antibodies, we demonstrate an extremely high level of SGLT2 message in proximal
      tubule S1 segments. This level of expression was also evident on Northern blots
      and likely confers the high capacity of this glucose transport system. We
      conclude that SGLT2 has properties characteristic of the renal low affinity high
      capacity Na+/glucose cotransporter as previously reported for perfused tubule
      preparations and brush border membrane vesicles. Knowledge of the structural and
      functional properties of this major renal Na+/glucose reabsorptive mechanism will
      advance our understanding of the pathophysiology of renal diseases such as
      familial renal glycosuria and diabetic renal disorders.

PMID- 8282811
TI  - Dystrophin: the long and short of it.

PMID- 8282812
TI  - Acidosis during ischemia promotes adenosine triphosphate resynthesis in
      postischemic rat heart. In vivo regulation of 5'-nucleotidase.
AB  - Capacity for ATP resynthesis during recovery from ischemia or hypoxia is limited
      to the size of the adenine nucleotide pool, which is determined in part by the
      activity of cytosolic 5'-nucleotidase (5'-NT): AMP-->adenosine plus inorganic
      phosphate (Pi). To define in vivo regulation of 5'-NT, we used the tools of 31P
      nuclear magnetic resonance (NMR), spectroscopy and chemical assay to measure the
      substrates (AMP), products (Pi, adenosine, and its catabolites), and inhibitors
      (Pi and H+) of 5'-NT in isolated perfused rat hearts exposed to hypoxia (where pH
      remains near 7) and no flow, global ischemia (where pH falls to 6.1). We
      estimated 5'-NT reaction velocity, assessed the relative contributions of Pi and
      H+ to enzyme inhibition, and defined the consequences of changes in 5'-NT
      activity on ATP resynthesis after hypoxia and ischemia. We conclude that (a) 5'
      NT is activated during hypoxia and early ischemia but is inhibited during
      prolonged ischemia, (b) H+ (pH < 6.2) is a potent inhibitor of 5'-NT, and (c)
      differences in AMP accumulation are sufficient to explain the differences in the
      capacity for net ATP resynthesis in ischemic and hypoxic tissue. These
      observations have implications for our understanding of heterogeneity of ischemic
      injury and myocardial protection during ischemia.

PMID- 8282814
TI  - Functional characterization of three intercalated cell subtypes in the rabbit
      outer cortical collecting duct.
AB  - The distribution of Na(+)-independent Cl(-)-HCO3- exchange was studied in
      individual intercalated cells from in vitro perfused rabbit outer CCDs using dual
      excitation laser scanning confocal microscopy by measuring the pHi response to
      sequential removal of Cl- from both sides of the tubule. Three patterns of
      intracellular pH (pHi) response were observed. 39% of intercalated cells had only
      apical Cl(-)-HCO3- exchange (beta cell), 4% had only basolateral Cl(-)-HCO3-
      exchange (alpha cell), and 57% had both apical and basolateral Cl(-)-HCO3-
      exchange (gamma cell). Valinomycin-high K+ voltage clamping had no effect on the
      pHi response of intercalated cells with bilateral Cl(-)-HCO3- exchange. Although
      the mean rates of dpHi/dt following apical Cl- removal were similar in beta cells
      compared to gamma cells, a wide range of apical rates was seen among individual
      beta and gamma intercalated cells. Neither the apical nor the basolateral Cl(-)
      HCO3- exchanger in gamma cells was inhibited by 0.5 mM H2DIDS. Binding of apical
      peanut lectin was seen both in beta cells and in gamma cells. In 41% of CCDs with
      four to seven intercalated cells studied, all intercalated cells were of the same
      subtype. We conclude that the majority of intercalated cells from the rabbit
      outer CCD have both apical and basolateral Na(+)-independent Cl(-)-HCO3-
      exchangers (gamma cells), which are stilbene-insensitive. Intercalated cells with
      only basolateral Cl(-)-HCO3- exchange are very uncommon in the rabbit outer CCD.
      There is a tendency for all intercalated cells in a given rabbit outer CCD to be
      of the same subtype (either all beta cells or all gamma cells), suggesting the
      presence of CCD intertubule heterogeneity at the same cortical level. This
      finding may account for intertubule differences in transepithelial H(+)-base
      transport.

PMID- 8282813
TI  - Expression and functional significance of alternatively spliced CS1 fibronectin
      in rheumatoid arthritis microvasculature.
AB  - Expression of fibronectin (FN) isoforms containing CS1, a 25-amino acid sequence
      present within the alternatively spliced IIICS region of FN, has been analyzed in
      rheumatoid arthritis (RA) synovium. Unexpectedly, CS1-containing FN variants were
      exclusively found on endothelium but not extracellular matrix (ECM) of RA
      synovium. Lumenal expression of CS1 on RA endothelial cells, as observed by
      electron microscopy, correlated with inflammation in RA, since normal synovium
      expressed little CS1 without appreciable decrease in ECM FN. CS1 expression on
      human endothelial cells was further shown by FN mRNA analyses. In adhesion assays
      on frozen RA synovial sections, T lymphoblastoid cells expressing functionally
      activated alpha 4 beta 1 integrin specifically attached to the intravascular
      surface of RA endothelium. Binding was abrogated by both anti-alpha 4 integrin
      and CS1 peptides. Our observations suggest direct involvement of CS1-containing
      FN in recruitment of alpha 4 beta 1-expressing mononuclear leukocytes in
      synovitis, and provide basis for therapeutic intervention in RA.

PMID- 8282815
TI  - Interleukin-10 prevents spontaneous death of germinal center B cells by induction
      of the bcl-2 protein.
AB  - In this study, we show that IL-10 enhances in vitro the viability of purified
      splenic B cells. There was a two- to threefold increase in recovery of viable
      cells during a 15-d culture period in the presence of IL-10. This effect was
      abolished by neutralizing antibodies to IL-10. The survival of large splenic B
      cells, which mostly represent follicular center cells, was similarly increased.
      The in vitro rescue from spontaneous death of the latter cells is known to
      involve a bcl-2-dependent pathway. We therefore investigated whether IL-10 might
      affect bcl-2 expression. Unseparated B cells as well as large splenic B cells
      displayed a strong expression of bcl-2 protein by immunofluorescence at days 2-7
      of culture in the presence of IL-10. Other lymphokines such as IL-2 and IL-4 were
      able to trigger only a transient and faint expression of bcl-2; moreover, this
      effect was abolished by anti-IL-10 mAb. Inasmuch as activated B cells can produce
      their own IL-10, this lymphokine may play a crucial role in relieving from
      apoptosis those B cells that encounter their antigen in B cell follicles.

PMID- 8282816
TI  - Molecular rearrangements of the MLL gene are present in most cases of infant
      acute myeloid leukemia and are strongly correlated with monocytic or
      myelomonocytic phenotypes.
AB  - Cytogenetic studies have previously identified abnormalities of chromosome band
      11q23 in many cases of infant acute leukemia. Recent studies by ourselves and
      others have demonstrated breakpoint clustering in acute leukemias bearing
      translocations involving 11q23, and a Drosophila trithorax gene homologue (called
      MLL, HRX, or ALL-1) has been shown to span the 11q23 breakpoints of these
      translocations. To determine if this gene is affected in infant acute myeloid
      leukemia (AML), we have analyzed 26 infant AML cases for molecular alterations of
      this 11q23 gene. 15 out of 26 cases studied (58%) showed rearrangement of the MLL
      gene at the molecular level, and these rearrangements were clustered within an
      approximately 11-kb region containing nine exons of this gene. Moreover, 14 of
      the 15 cases with 11q23 rearrangements (93%) had myelomonocytic or monocytic
      phenotypes (M4 or M5 FAB subtypes, respectively), both of which are associated
      with a poor prognosis in childhood AML. In contrast, only 1 of 11 nonrearranged
      cases had an M4 or M5 phenotype (P = 0.00002). Rearrangement also correlated
      significantly with hyperleukocytosis (P = 0.02), another clinical parameter
      associated with poor outcome in this disease. Our results demonstrate that
      molecular rearrangements of MLL are common in M4 or M5 infant AML, and suggest
      that alteration of this gene may result in abnormal control of proliferation and
      differentiation in monocytic progenitor cells.

PMID- 8282817
TI  - Increased expression of basement membrane collagen in human diabetic retinopathy.
AB  - Basement membrane thickening is the most prominent and characteristic feature of
      early diabetic microangiopathy. Unknown is not only the causative process but
      also whether the thickening reflects increased synthesis of specific components.
      Because collagen type IV is uniquely present in basement membranes and represents
      their predominant structural element, we studied its expression in retinas
      obtained postmortem from five patients with 8 +/- 3 yr of diabetes and six
      nondiabetic controls. The collagen IV transcript proved to be rare in adult human
      retina and undetectable by Northern analysis. We thus identified a set of primers
      and conditions to detect the transcript by the reverse transcriptase polymerase
      chain reaction and to measure its level relative to an endogenous internal
      standard (beta-actin mRNA). In the diabetic patients the levels of collagen IV
      mRNA were increased twofold over levels in controls, whereas the actin mRNA
      levels were similar in the two groups. Hence, the collagen IV/actin ratio was
      0.53 +/- 0.15 in diabetic samples and 0.24 +/- 0.09 in control samples (P =
      0.004). These results indicate that diabetes induces a twofold increase in the
      expression of collagen IV by the cells that synthesize basement membranes in the
      adult retina (vascular cells). Insofar as high ambient glucose in vitro elicits
      the same effect, it may be proposed that basement membrane thickening in diabetes
      results from enhanced synthesis of specialized component molecules sustained by
      hyperglycemia.

PMID- 8282818
TI  - Lupus autoantibodies to native DNA cross-react with the A and D SnRNP
      polypeptides.
AB  - Antibodies to native DNA (nDNA) in sera from patients with systemic lupus
      erythematosus have been found to frequently correlate with antibodies to the A
      and D SnRNP proteins measured in Western blot assays. 40 of 54 SLE (74.1%) sera
      with anti-nDNA bound to A and D proteins, while 9 of 113 sera (8%) without anti
      nDNA bound the A and D proteins, P < 10(-8) by Fisher's exact test. Antibodies to
      nDNA correlated closely with anti-A and anti-D in seven of eight patients
      followed sequentially, r = 0.7865. Nine human polyclonal anti-nDNA populations
      were isolated from DNA cellulose columns. Seven reacted equally with A and D, and
      two reacted predominantly with D. Two of three murine monoclonal anti-DNA
      antibodies isolated from NZB/NZW F1 hybrid mice bound A and D equally in Western
      blot with a titer > 1/40,000. These reactions were directed to the unfolded A and
      D proteins measurable in Western blot since these monoclonals (and several of the
      human anti-nDNA populations) failed to react with native U1RNP in ELISA or in RNA
      immunoprecipitation experiments. These newly recognized cross reactions of anti
      nDNA may amplify the immune response to DNA and be part of the original
      immunogenic drive.

PMID- 8282819
TI  - Selective reduction of delta 6 and delta 5 desaturase activities but not delta 9
      desaturase in micropigs chronically fed ethanol.
AB  - This study investigated the mechanism by which chronic ethanol feeding reduces
      arachidonate and other highly unsaturated fatty acids in pig liver phospholipids.
      Five micropigs were fed a diet providing 89 kcal/kg body wt for 12 mo, with
      ethanol and fat as 40 and 34% of energy, respectively. Five control pigs were
      pairfed corn starch instead of ethanol. The activities of delta 6 and delta 5
      desaturases (expressed as microsomal conversion of precursor to product) in liver
      from ethanol-fed pigs were reduced to less than half that of controls, whereas
      the activity of delta 9 desaturase was unaffected in the ethanol group. delta 5
      Desaturase activity showed positive correlation with the abundance of its
      products in liver total phospholipids and microsomes in the ethanol group, but
      not in the controls. Correlation between delta 6 desaturase activity and its
      products showed similar pattern to that of delta 5 desaturase, but did not reach
      statistical significance. No difference was observed between the two groups in
      coenzyme A concentration in the liver. These results suggest that the selective
      reduction of delta 6 and delta 5 desaturase activities, not the microsomal
      electron transport system, are directly responsible for the altered profile of
      liver phospholipids.

PMID- 8282820
TI  - Rhabdomyosarcomas do not contain mutations in the DNA binding domains of myogenic
      transcription factors.
AB  - Skeletal myogenesis is regulated by a group of transcription factors (MyoD,
      myogenin, myf5, and myf6) that are "basic helix-loop-helix" proteins that bind to
      the promoters of muscle-specific genes and promote their expression. We have
      previously shown that after a mutation of Leu122 to Arg the DNA binding basic
      domain of MyoD confers c-myc-like functional characteristics to the protein. In
      this study we used single-strand conformation polymorphism analysis to determine
      whether such mutations occur naturally in rhabdomyosarcomas. We have found that
      the basic domains of all the myogenic factors remain unaltered in
      rhabdomyosarcomas. Selection against such mutations may be the result of
      functional redundancy of these myogenic transcription factors.

PMID- 8282821
TI  - Impairment of endothelium-dependent dilation is an early event in children with
      familial hypercholesterolemia and is related to the lipoprotein(a) level.
AB  - Familial hypercholesterolemia is associated with premature atherosclerosis. Since
      endothelial dysfunction is an early event in atherogenesis, we used a noninvasive
      method to assess endothelial function in the systemic arteries of 30 children
      aged 7-17 yr (median 11) with familial hypercholesterolemia (2 homozygotes, 28
      heterozygotes, total cholesterol 240-696 mg/dl) and 30 healthy age- and sex
      matched controls. Using high resolution ultrasound, the diameter of the
      superficial femoral artery was measured at rest, in response to reactive
      hyperemia (with increased flow causing endothelium-dependent dilation), and after
      sublingual glyceryltrinitrate (causing endothelium-independent vasodilation).
      Flow-mediated dilation was present in the controls (7.5 +/- 0.7%) but was
      impaired or absent in the hypercholesterolemic children (1.2 +/- 0.4%, P <
      0.0001). Total cholesterol was inversely correlated with flow-mediated dilation
      (r = -0.61, P < 0.0001). In the hypercholesterolemic children, flow-mediated
      dilation was inversely related to the lipoprotein(a) level (r = -0.61, P = 0.027)
      but not to other lipid fractions. Glyceryltrinitrate-induced dilation was present
      in all subjects but was lower in the hypercholesterolemia group (10.0 +/- 0.6% vs
      12.4 +/- 0.8%, P = 0.023). Thus, impaired endothelium-dependent dilation is
      present in children with familial hypercholesterolemia as young as 7 yr of age
      and the degree of impairment is related to the lipoprotein(a) level.

PMID- 8282822
TI  - Analysis of tumor necrosis factor promoter responses to ultraviolet light.
AB  - Ultraviolet (UV) light induces the biosynthesis of chloramphenicol
      acetyltransferase (CAT) in the skin of mice bearing the CATTNF reporter
      transgene. Moreover, nuclear run-on assays indicate that UV light induces
      transcription of the TNF gene in RAW 264.7 macrophages. These observations
      suggest that the TNF gene (and/or its mRNA product) responds to signals elicited
      by UV light. To identify transcriptional UV response elements within the TNF
      promoter, and to determine whether a posttranscriptional response might also
      exist, a series of reporter constructs using a CAT coding sequence attached to
      various portions of the TNF promoter and 3' untranslated region were devised and
      transfected into several cultured cell lines. All cells tested were found to be
      UV responsive, and in NIH 3T3 cells, induction was found to depend upon two
      general regions of the promoter. The more distal region encompassed nucleotides
      (nt) -1059 through -451 with respect to the cap site, while the more proximal
      region spanned nt -403 through -261. A negative element, blocking the UV
      response, was interposed (nt -451 through -403). As with the response to LPS, the
      response to UV irradiation appears to involve translational activation in
      macrophages. However, the UV and LPS signaling pathways have little in common
      with one another, as indicated by three observations. First, no difference in
      responsiveness was observed on comparison of TNF gene induction in macrophages
      derived from C3H/HeN as opposed to C3H/HeJ mice. Second, cell fusion studies
      showed that while the LPS signaling pathway is extinguished by fusion of RAW
      264.7 cells with NIH 3T3 cells, the UV signaling pathway remained intact.
      Finally, induction did not depend upon the NF-kappa B binding sites that are
      known to be required for LPS response in macrophages, since mutation of these
      sites did not impair the UV response.

PMID- 8282823
TI  - Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol
      without causing uterine hypertrophy in ovariectomized rats.
AB  - There is a medical need for an agent with the positive effects of estrogen on
      bone and the cardiovascular system, but without the negative effects on
      reproductive tissue. Raloxifene (LY139481 HCI) is a benzothiophene derivative
      that binds to the estrogen receptor and inhibits the effects of estrogen on the
      uterus. In an ovariectomized (OVX) rat model we investigated the effects of
      raloxifene on bone loss (induced by estrogen deficiency), serum lipids, and
      uterine tissue. After oral administration of raloxifene for 5 wk (0.1-10 mg/kg
      per d) to OVX rats, bone mineral density in the distal femur and proximal tibia
      was significantly greater than that observed in OVX controls (ED50 of 0.03-0.3
      mg/kg). Serum cholesterol was lower in the raloxifene-treated animals, which had
      a minimal effective dose of 0.1 mg/kg and an approximate oral ED50 of 0.2 mg/kg.
      The effects of raloxifene on bone and serum cholesterol were comparable to those
      of a 0.1-mg/kg per d oral dose of ethynyl estradiol. Raloxifene diverged
      dramatically from estrogen in its lack of significant estrogenic effects on
      uterine tissue. Ethynyl estradiol produced a marked elevation in a number of
      uterine histologic parameters (e.g., epithelial cell height, stromal
      eosinophilia). These data suggest that raloxifene has promise as an agent with
      beneficial bone and cardiovascular effects in the absence of significant uterine
      effects.

PMID- 8282824
TI  - A possible role for rat intestinal surfactant-like particles in transepithelial
      triacylglycerol transport.
AB  - To further examine whether surfactant-like particles (DeSchryver-Kecskemeti, K.,
      R. Eliakim, S. Carroll, W. F. Stenson, M. A. Moxley, and D. H. Alpers. 1989. J.
      Clin. Invest. 84:1355-1361) were involved in the transepithelial transport of
      lipid, alkaline phosphatase activity and surfactant-like particle content were
      measured in apical mucosal scrapings, enterocytes, lamina propria, and serum
      after inhibition of chylomicron transport. Serum triacylglycerol levels were
      decreased 60-76% by Pluronic L-81, fenfluramine, and choline deficiency compared
      with fat-fed controls. 5 h after triacylglycerol feed, alkaline phosphatase
      activity in all three experimental groups was decreased compared with controls by
      52-69% in mucosal scrapings and by 33-72% in serum. A parallel decline (60%) in
      alkaline phosphatase activity occurred in the lamina propria of Pluronic-treated
      animals. Total particle content (measured by an ELISA using antiserum against
      purified particle) after Pluronic treatment was decreased in mucosal scrapings,
      lamina propria, and serum by 16, 22, and 29% at 3 h and by 33, 40, and 8%,
      respectively, at 5 h after fat feeding. In contrast, particle content was
      increased in enterocytes by 29% 3 h and by 8% 5 h after fat feeding. By electron
      microscopy, enterocytes from Pluronic- and fenfluramine-treated animals exhibited
      a two- to threefold increase in large intracellular cytoplasmic lipid globules
      and the appearance of lamellae in apposition, with a marked decrease in the
      number of surfactant-like particles overlying the brush border. These changes,
      produced by inhibition of chylomicron transport, in the distribution of
      surfactant-like particles and particle-bound alkaline phosphatase are consistent
      with a role for these particles in transepithelial triacylglycerol transport
      across and out of the enterocyte.

PMID- 8282825
TI  - Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are
      specific for platelet factor 4 complexed with heparin or bound to endothelial
      cells.
AB  - Heparin-induced thrombocytopenia/thrombosis (HITP) is thought to be mediated by
      immunoglobulins that activate platelets in the presence of pharmacologic
      concentrations of heparin, but the molecular basis for this relatively common and
      often serious complication of heparin therapy has not been established. We found
      that plasma from each of 12 patients with HITP contained high titer (> or =
      1:200) antibodies that reacted with immobilized complexes of heparin and platelet
      factor 4 (PF4), a heparin-binding protein contained in platelet alpha-granules.
      Recombinant human PF4 behaved similarly to PF4 isolated from platelets in this
      assay system. Complexes formed at an apparent heparin/PF4 molecular ratio of
      approximately 1:2 (fresh heparin) and approximately 1:12 (outdated heparin) were
      most effective in binding antibody. Immune complexes consisting of PF4, heparin,
      and antibody reacted with resting platelets; this interaction was inhibited by a
      monoclonal antibody specific for the Fc gamma RII receptor and by excess heparin.
      Human umbilical vein endothelial cells, known to express heparin-like
      glycosaminoglycan molecules on their surface, were recognized by antibody in the
      presence of PF4 alone; this reaction was inhibited by excess heparin, but not by
      anti-Fc gamma RII. Antibodies reactive with heparin/PF4 were not found in normal
      plasma, but IgG and IgM antibodies were detected at dilutions of 1:10 (IgG) and
      1:50 (IgM) in 3 of 50 patients (6%) with other types of immune thrombocytopenia.
      These findings indicate that antibodies associated with HITP react with PF4
      complexed with heparin in solution or with glycosaminoglycan molecules on the
      surface of endothelial cells and provide the basis for a new hypothesis to
      explain the development of thrombocytopenia with thrombosis or disseminated
      intravascular coagulation in patients sensitive to heparin.

PMID- 8282826
TI  - Stimulation with a monoclonal antibody (mAb4E4) of scavenger receptor-mediated
      uptake of chemically modified low density lipoproteins by THP-1-derived
      macrophages enhances foam cell generation.
AB  - mAb4E4, a murine monoclonal antibody that is specific for acetylated LDL and
      malondialdehyde-treated LDL, binds specifically to modified LDL present in human
      atherosclerotic lesions. It is directed against an epitope that is poorly exposed
      in delipidated and solubilized apolipoprotein B-100 from modified LDL. mAb4E4, as
      well as its F(ab')2 and Fab fragments, enhanced the uptake of both acetylated LDL
      and malondialdehyde-treated LDL by THP-1-derived macrophages resulting in a
      sixfold increase of cytoplasmic cholesteryl ester levels. The increased uptake of
      modified LDL/mAb4E4 complexes did not occur via the Fc receptor and did not
      depend on aggregation of modified LDL particles. However, their uptake was
      inhibited by blocking the scavenger receptors with fucoidin or by downregulation
      of receptor expression with endotoxins or interferon-gamma, indicating that their
      uptake is mediated via these receptors. Thus, generation of autoimmune antibodies
      against modified LDL and subsequent endocytosis of soluble modified LDL/antibody
      complexes via scavenger receptors may enhance foam cell generation. This
      mechanism may contribute to the progression of atherosclerotic lesions.

PMID- 8282828
TI  - Audit of oral anticoagulant treatment. The BCSH Haemostasis and Thrombosis Task
      Force of the British Society for Haematology.

PMID- 8282827
TI  - Immunohistochemical analysis of dystrophin-associated proteins in Becker/Duchenne
      muscular dystrophy with huge in-frame deletions in the NH2-terminal and rod
      domains of dystrophin.
AB  - The absence of dystrophin causes the drastic reduction of the dystrophin
      associated proteins (DAPs) in the sarcolemma and the loss of the linkage between
      the subsarcolemmal cytoskeleton and the extracellular matrix in Duchenne muscular
      dystrophy (DMD) skeletal muscle. Here, we report a mild reduction of the DAPs in
      the unique Becker muscular dystrophy patients with huge deletions in the rod
      domain of dystrophin and a moderate reduction of the DAPs in patients with huge
      deletions that involve both the NH2-terminal and rod domains of dystrophin. The
      phenotype of the latter patients was more severe than that of the former. In both
      cases, however, the reduction in the DAPs was milder than in typical DMD patients
      or DMD patients lacking the COOH-terminal domains of dystrophin. Our results
      suggest that (a) the NH2-terminal and rod domains of dystrophin may not be
      essential for the interaction with the sarcolemmal glycoprotein complex; and (b)
      defects in the actin binding activity of dystrophin may cause disruption of the
      anchorage of the dystrophin-glycoprotein complex to the subsarcolemmal
      cytoskeleton, which may render muscle fibers susceptible to degeneration.

PMID- 8282829
TI  - HIV and the necropsy.

PMID- 8282830
TI  - Post mortem examinations of HIV infected patients: a nationwide survey.
AB  - AIMS: To identify the number and geographical distribution of post mortem
      examinations performed on HIV infected cadavers; to identify the areas that
      perform post mortem examinations so that, by invitation and discussion, a
      national post mortem network could be initiated. METHODS: A nationwide survey of
      Royal College of Pathologists' district tutors (n = 216) was done by postal
      questionnaire. These were completed by the district tutors or passed on to their
      histopathologist colleagues. The results were collated after three months. After
      one follow up letter, an 86% response rate, which is a significant sample, was
      achieved. RESULTS: Twenty eight per cent of respondents were performing HIV post
      mortem examinations. Of those who were not performing them (30%), the lack of
      clinical or coroner requests was the most common explanation. All regions provide
      facilities for HIV post mortem examinations, as judged by the responses.
      CONCLUSIONS: These findings are of singular importance as it is the first United
      Kingdom survey investigating the distribution of post mortem examinations on HIV
      infected cadavers. Studying post mortem material using a systemic, coordinated
      collection of brain tissue is essential to increase knowledge of a new disease of
      pandemic proportions.

PMID- 8282831
TI  - Expression of interleukin-6 by intestinal enterocytes.
AB  - AIMS: To investigate the cellular source of the cytokine interleukin-6 (IL-6) in
      the small and large intestines of patients with inflammatory bowel disease,
      coeliac disease, and in controls. METHODS: IL-6 was detected in frozen sections
      of bowel by single and double label indirect immunofluorescence using rabbit
      polyclonal and murine monoclonal anti-IL-6 antibodies. The murine monoclonal
      antibodies RFDR1 (anti-MHC class II) and UCHT1 (anti-CD3) were used to localise
      macrophages and T lymphocytes, respectively. Lipopolysaccharide stimulated
      peripheral blood monocytes were used as positive control cells for IL-6 protein.
      RESULTS: IL-6 was demonstrated in the small and large intestine of patients with
      inflammatory bowel disease, coeliac disease, and in controls. The protein was
      present predominantly in enterocytes and colocytes in normal and inflamed mucosa,
      but not in the infiltrating inflammatory cells of the lamina propria. There were
      no discernable differences between patients with inflammatory bowel disease or
      coeliac disease and controls, nor between small and large bowel mucosa.
      Incubation of antibody with recombinant human IL-6 protein abolished the
      labelling. IL-6 protein was also present in lipopolysaccharide stimulated
      peripheral blood monocytes. CONCLUSIONS: The data suggest that enterocytes and
      colocytes may play an active part in the immune response of the gut. The presence
      of IL-6 in both inflamed and non-inflamed small and large intestine requires
      further investigation into the function of this cytokine in the gut.

PMID- 8282832
TI  - Retrospective study of prognostic value of DNA ploidy and proliferative activity
      in neuroblastoma.
AB  - AIM: To assess the prognostic value of age and stage at diagnosis, site of
      primary tumour, cell ploidy and N-myc copy number in children with neuroblastoma.
      METHODS: Flow cytometry was used to determine the cellular DNA content of
      paraffin wax embedded archival material from 69 cases of neuroblastoma and was
      successful in 52. RESULTS: The age, stage, and survival distribution of the
      sampled cases was not significantly different from that in a larger population
      based series. There were seven diploid ("non-aneuploid") and 45 aneuploid
      (including two tetraploid and four triploid) tumours. The 10 year survival was
      significantly better for cases of aneuploid rather than diploid tumours (p <
      0.05). An important new finding was that 10 year survival was also significantly
      better for tumours with a low percentage of cells in S phase (p < 0.03).
      CONCLUSION: The percentage of cells in S phase, a measure of the proliferative
      activity of the tumour, correlated with prognosis in neuroblastoma. This should
      be measured with other biological features of the disease, such as N-myc copy
      number, when prognostic indicators are being assessed.

PMID- 8282834
TI  - Estimation of urinary aldosterone using thin-layer chromatography and
      fluorimetry.
AB  - AIMS: To develop a fluorimetric method for the estimation of urinary aldosterone;
      to establish a normal range in 24 hour and overnight urine samples; and to
      investigate the use of overnight urines for detecting hyperaldosteronism.
      METHODS: Essential steps include hydrolysis of the 18 conjugate to release
      aldosterone and its oxidation with Benedict's solution, followed by thin-layer
      chromatography on silica gel and development of fluorescence on the plate with
      sulphuric acid. RESULTS: There was a linear correlation between the amount of
      aldosterone and the area under the peak on the chromatogram. The mean intra-assay
      and interassay coefficients of variation were 4.4% and 6.8%, respectively. The
      mean aldosterone excretion in 67 adults was 15.7 (SD 8.1) nmol/24 hours. The mean
      overnight excretion in 65 adults was 2.6 (1.4) nmol/8 hours. The method detected
      raised concentrations in patients with primary and secondary aldosteronism.
      CONCLUSIONS: This technique provides an accurate means of assaying urinary
      aldosterone. Overnight estimations seem to be as effective as 24 hour assays for
      identifying patients with hyperaldosteronism.

PMID- 8282833
TI  - Rapid HLA typing by multiplex amplification refractory mutation system.
AB  - AIMS: To detect HLA susceptibility and protective alleles associated with insulin
      dependent diabetes mellitus (IDDM) using a multiplex amplification refractory
      mutation system (ARMS). These include DR3 and DR4 alleles at the DRB1 locus,
      presence or absence of aspartic acid at position 57 (Asp-57) of the DQB1 locus,
      and presence or absence of arginine at position 52 (Arg-52) of the DQA1 locus.
      METHODS: The ARMS approach was used to design allele specific primers for the
      detection of the major susceptibility and protective alleles for IDDM. These
      include DR3 and DR4 alleles at the DRB1 locus, Asp-57 and non-Asp-57 at the DQB1
      locus, and Arg-52 and non-Arg-52 alleles at the DQA1 locus. The allele
      specificity of each set of primers was first tested separately using DNA samples
      from 15 individuals previously typed for the DRB1, DQB1, and DQA1 loci using the
      sequence specific oligonucleotide (SSO) technique. The possibility of using
      multiplex ARMS for typing multiple susceptibility/protective alleles for IDDM was
      further investigated by testing various combinations of allele specific primers,
      thereby reducing the number of separate polymerase chain reactions required to
      type all these alleles. RESULTS: A "three-tube" system worked well and gave
      accurate results. Tube 1 contained ARMS primers for the detection of IDDM
      susceptibility alleles DR3 and DR4; tube 2 contained ARMS primers for the
      detection of susceptibility alleles non-Asp-57 and Arg-52; and tube 3 contained
      ARMS primers for the detection of the protective alleles Asp-57 and non-Arg-52.
      DNA samples typed with this ARMS method were in complete agreement with those
      obtained using the SSO technique. CONCLUSION: This method is rapid and has no
      requirement for radioactivity. It is an efficient method for population
      screening.

PMID- 8282835
TI  - Influence of anticardiolipin antibodies on immediate patient outcome after
      myocardial infarction.
AB  - AIMS: To determine whether the presence of anticardiolipin antibodies in patients
      with suspected myocardial infarction is predictive of complications during
      hospital stay or after discharge. METHODS: Anticardiolipin antibodies were
      serially measured in a cohort of 111 patients, from the time of admission to the
      coronary care until till eight weeks after discharge. Associations with fatal and
      non-fatal cardiac complications were documented. RESULTS: The incidence of raised
      titres of IgG and IgM anticardiolipin antibodies (ACA) in patients with
      myocardial infarction was comparable with that in patients with ischaemic heart
      disease. ACA titres in patients with a previous myocardial infarct were not
      significantly different from those found in patients without a previous history
      of infarction. Over the period of the study, ACA titres in the myocardial infarct
      group did not change significantly from those recorded on admission, nor did
      those patients with raised ACA titres have a higher prevalence of complications
      in hospital or in the early period after discharge. CONCLUSIONS: There is no
      evidence that patients with an acute or previous myocardial infarct have higher
      ACA titres than those found in patients with ischaemic heart disease. Raised ACA
      titres soon after myocardial infarction do not influence immediate patient
      outcome.

PMID- 8282836
TI  - Serological investigation into the association between Streptococcus bovis and
      colonic cancer.
AB  - AIMS: To determine if there was an increase in antibody titre to Streptococcus
      bovis in patients with colonic cancer, and if this might be a useful marker of
      the presence for colonic cancer. METHODS: Serum samples from 16 patients and 16
      age matched controls were tested by immunoblot and enzyme linked immunosorbent
      assay (ELISA) against antigen preparations from two strains of S bovis and one
      strain of Enterococcus faecalis. RESULTS: No distinction between cancer patients
      and controls could be made using immunoblots. ELISA did show an increase in
      antibodies to S bovis, but there was a greater increase in antibodies to E
      faecalis. The increase in antibody titres was greatest with antigens which had
      been treated with periodate, and was therefore thought not to be caused by
      antibody to the shared group D carbohydrate antigen. CONCLUSION: It may be
      possible to construct a test for the detection of colonic cancer based on the
      detection of antibody to S bovis or E faecalis, though considerable further
      development of this concept is required.

PMID- 8282837
TI  - Comparison of three serological methods for diagnosing Mycoplasma pneumoniae
      infection.
AB  - AIMS: To compare the novel Serofast latex agglutination test (International
      Mycoplasma, Toulon-Cedex, France) with the complement fixation test and enzyme
      immunoassay (EIA) for diagnosing acute Mycoplasma pneumoniae infection. METHODS:
      Paired sera from 60 patients with respiratory infection who had tested positive
      for M pneumoniae by complement fixation test were analysed with Serofast and
      indirect EIA for specific IgG and IgM antibodies. RESULTS: Serofast was less
      sensitive than the two other tests. Only 30 (50%) out of 60 paired sera which
      showed a diagnostic seroconversion or had high positive, unchanged antibody
      titres by complement fixation test or EIA, or both, tested positive with
      Serofast. Positive test results with Serofast were associated with the presence
      of a complement fixation test titre of > or = 512 and high positive IgM antibody
      titres measurable by EIA; virtually all patients with a complement fixation test
      titre of < 256 or those responding primarily in the IgG class tested negative
      with Serofast. Based on analysis of sera taken at the acute phase of infection,
      10 (17%) of the 60 patients tested positive by complement fixation test, 10 (17%)
      by EIA, and only four (7%) by Serofast. CONCLUSIONS: Serofast was less sensitive
      than complement fixation test and EIA and it cannot be recommended as a
      replacement for either test in routine diagnostic use. It might prove useful in
      laboratories where non-specific tests, such as the determination of cold
      agglutinins, are still used for the diagnosis of M pneumoniae infection. Testing
      paired sera is, however, a prerequisite for obtaining acceptable sensitivity by
      Serofast as well as other serological methods currently available.

PMID- 8282838
TI  - Antimicrobial activity of cytotoxic drugs may influence isolation of bacteria and
      fungi from blood cultures.
AB  - The potential antimicrobial activity of cyclophosphamide, vincristine, and
      adriamycin against Gram positive and negative bacteria and Candida albicans was
      examined. The time taken for different microbial inocula to turn a simulated
      blood culture positive in the presence of different concentrations of these drugs
      was measured. Doxorubicin retarded the growth of Staphylococcus aureus,
      Staphylococcus epidermidis, and Streptococcus sanguis in a concentration
      dependent manner. Cyclophosphamide and vincristine showed minimal antimicrobial
      activity. Escherichia coli and Pseudomonas aeruginosa were unaffected by any of
      the drugs. An inoculum dependent effect was seen with some combinations of
      microbial inocula and cytotoxic drug concentrations.

PMID- 8282839
TI  - Fatal vertebral giant cell arteritis.
AB  - Death due to giant cell arteritis (GCA) is rare, and is usually caused by
      coronary or vertebral arteritis in the acute phase of the disease. A case of
      fatal GCA is reported in a woman with a normal erythrocyte sedimentation rate,
      who had been treated for temporal arteritis for eight months. Post mortem
      examination showed a dissection and thrombosis of the intracranial portion of the
      left vertebral artery caused by giant cell arteritis. Focal coronary artery GCA
      was also found. As far as is known, this is the only case in which dissection of
      the vertebral artery attributable to GCA has been reported.

PMID- 8282840
TI  - Renal failure caused by leukaemic infiltration in chronic lymphocytic leukaemia.
AB  - A case of B-CLL which was complicated by chronic renal failure due to leukaemic
      infiltration of the kidney is reported. Treatment with chlorambucil,
      prednisolone, and renal bed irradiation resulted in a substantial improvement in
      renal function which persisted until the the patient's death from marrow failure
      some eight years later. The temporal association between treatments and response
      suggested that renal bed radiotherapy had contributed to the improvement in renal
      function. This case is one of only two reported cases in which chronic renal
      failure due to CLL has been treated with radiotherapy. It is unique in that the
      renal response was shown histologically. Leukaemic infiltration of the kidney is
      common in CLL but, characteristically, is not associated with renal impairment.
      An improvement in renal function has been described in two patients with acute
      renal failure after chemotherapy.

PMID- 8282841
TI  - Glanzmann's thrombasthenia with mild von Willebrand's disease.
AB  - A Saudi Arabian family is reported in which Glanzmann's thrombasthenia and von
      Willebrand's disease occurred simultaneously. The daughter presented with
      menorrhagia and gave a history of gastrointestinal bleeding and a strong family
      history of bleeding disorder. Full haematological investigations were performed
      on the propositus, parents, and siblings, including complete blood count,
      bleeding time, prothrombin time, partial thromboplastin time, factor VIII:C, von
      Willebrand factor, ristocetin cofactor, platelet aggregometry, platelet
      glycoprotein Ib and IIb/IIIa and platelet antigen PLT-1 (Coulter Clone). The
      propositus had Glanzmann's thrombasthenia, both parents had mild von Willebrand's
      disease and were carriers of Glanzmann's thrombasthenia. Three symptomatic
      brothers had both Glanzmann's thrombasthenia and von Willebrand's disease; two
      asymptomatic brothers had von Willebrand's disease only and one had completely
      normal results. Those family members with both diseases were more severely
      affected than those with just one disease. In areas where consanguineous marriage
      is common, such as Saudi Arabia, multiple haemostatic abnormalities may occur,
      and investigation should not stop with the discovery of a single abnormality. The
      increased clinical severity of bleeding, including haemarthroses, in those
      patients having both congenital defects emphasises the importance of von
      Willebrand factor in glycoprotein Ib-mediated platelet adhesion.

PMID- 8282842
TI  - Analysis of human herpes virus-6 genomes in lymphoid malignancy in Japan.
AB  - Ninety cases of malignant lymphoma and 56 cases of reactive lymphadenopathy were
      studied using Southern blot analysis and the polymerase chain reaction to
      identify human herpes virus-6 (HHV-6) DNA. This was detected in cases of lymphoid
      malignancy at a rate which ranged from 50.0% to 68.8%. There were no differences
      in rates for different types of lymphoid malignancies. Herpes virus-6 DNA was
      detected by PCR in lymphoid malignancies less frequently than in reactive
      lymphadenopathies. It was not detected in lymphoid malignancies using Southern
      blotting. These results suggest that HHV-6 DNA was not related to lymphoid
      malignancy and was only a latent infection of non-neoplastic cells in tumour
      tissue.

PMID- 8282843
TI  - Inaccurate haemoglobin estimation in Waldenstrom's macroglobulinaemia: unusual
      reaction with monomeric IgM paraprotein.
AB  - Automated blood counts from a patient with Waldenstrom's macroglobulinaemia
      repeatedly failed critical limit standards set for mean cell haemoglobin
      concentration and mean cell haemoglobin. Haemoglobin estimation was higher than
      that suggested by clinical examination, symptoms, and the spun haematocrit. This
      was found to be due to an interaction between the Coulter lysing agent and
      monomeric IgM paraprotein in the patient's plasma, creating a precipitate which
      was optically dense at 525 nm.

PMID- 8282844
TI  - Market testing clinical services.

PMID- 8282845
TI  - Marking of excision margins of discrete skin lesions.

PMID- 8282846
TI  - Selective medium for MRSA.

PMID- 8282847
TI  - The A-1 antigen: a novel marker in experimental peripheral nerve injury.
AB  - Expression of the Schwann cell phenotype is regulated by signals from the
      adjoining axon. After axotomy, the Schwann cell ceases the production and
      maintenance of the myelin sheath and assumes phagocytic properties necessary to
      digest its own myelin. The molecular mechanisms responsible for this behavior
      remain unclear. A monoclonal antibody termed BIKS was produced after the
      immunization of mice with guinea pig lymphoid tissue. This antibody recognizes a
      cytoplasmic vesicle-associated molecule (A-1 antigen) which is abundant in all
      tissue macrophages but is also expressed in small amounts in normal Schwann
      cells. Following axotomy, the A-1 antigen appears to be translocated from a
      perinuclear site to accumulate in large quantities around myelin ovoids in
      Schwann cells, as well at the nodes of Ranvier-sites where Wallerian degeneration
      is known to commence. The level of the antigen remains high when axons are
      prevented from regeneration. During repair of crush injury, however, the level of
      antigen drops concomitant with the ingrowth of regenerating axons, suggesting
      axonal control of A-1 antigen expression.

PMID- 8282848
TI  - The innervation of the mystacial pad of the rat as revealed by PGP 9.5
      immunofluorescence.
AB  - The innervation of the mystacial pad in the rat was investigated with the aid of
      antihuman protein gene product (PGP) 9.5 immunofluorescence. PGP 9.5 is ubiquitin
      carboxyl-terminal hydrolase, which is distributed throughout neuronal cytoplasm.
      This technique revealed all previously known innervation as well as a wide
      variety of small-caliber axons and some endings of large-caliber afferents that
      had not been observed before. Newly revealed innervation affiliated with
      vibrissal-follicle sinus complexes included 1) fine-caliber, radially oriented
      processes in the epidermal rete ridge collar; 2) a loose network of fine-caliber,
      circumferentially arrayed processes in the centrifugal part of the mesenchymal
      sheath at the level of the ring sinus; 3) a loose haphazard network of fine
      caliber and medium-caliber processes in the mesenchymal sheath and among the
      trabeculae of the cavernous sinus; 4) a loose network of circumferentially
      arrayed processes within the mesenchymal sheath of the cavernous sinus and in
      close proximity to the basement membrane; 5) a dense network of reticular-like
      endings provided by large-caliber afferents to the mesenchymal sheath in the
      upper part of the cavernous sinus; and 6) fine-caliber innervation to the dermal
      papilla at the base of all vibrissal shafts. In the intervibrissal skin, a dense
      distribution of fine-caliber individual and clustered profiles was detected in
      the epidermis. In addition to previously known innervation, Merkel endings were
      consistently observed in the epidermis at the mouths of guard hairs, loose
      networks of fine-caliber axons were found around the necks of occasional guard
      hairs, and fine-caliber profiles were frequently affiliated with vellus hairs.
      Vascular profiles were heavily innervated throughout the dermis. Axons and motor
      end plates of the facial nerve innervation to papillary muscles also were
      labeled. Transection of the infraorbital nerve eliminated all but the facial
      nerve innervation. Unilateral removal of the superior cervical ganglion
      eliminated the innervation to the dermal papillae but caused no other noticeable
      reduction. PGP 9.5-like immunofluorescence was also moderately expressed in
      apparent Schwann cells, in Merkel cells only in the external root sheath of
      vibrissal follicles, and in apparent dendritic and/or Langerhans cells usually
      located in the epidermis and occasionally in the follicles. PGP 9.5-like
      immunofluorescence persisted in highly vacuolated profiles along the usual
      courses of medium to large-caliber axons 2 weeks after nerve transection. The
      possible functional role of the newly discovered innervation is considered along
      with that of previously identified afferents.

PMID- 8282849
TI  - Structure, vascularization, and innervation of the mystacial pad of the rat as
      revealed by the lectin Griffonia simplicifolia.
AB  - The mystacial pad of the rat is endowed with rows of vibrissal follicle-sinus
      complexes (F-SCs) that receive a dense and rich variety of innervation, much of
      which is C fibers. Each F-SC consists of a follicle at the core of a spindle
      shaped, encapsulated vascular sinus. Previous studies have shown that the B
      subunit of the lectin Griffonia simplicifolia (GSA I-B4) binds selectively to a
      subset of small neurons in the trigeminal ganglion and to a subset of C fibers
      preferentially distributed to inner lamina II and outer lamina III of nucleus
      caudalis in the brainstem trigeminal complex in the rat. These laminae are also a
      major site of termination for afferents in superficial vibrissal nerves (SVNs)
      that innervate the upper portion of F-SCs. To determine the peripheral
      distribution of the afferents that bind GSA I-B4, mystacial pads from rats were
      prepared for fluorescence microscopy with GSA I-B4 conjugated to rhodamine. At
      the neck of each F-SC, numerous circumferentially oriented bundles of fine
      caliber axonal profiles were labeled in the inner conical body, which receives
      nearly all of its innervation from the SVNs. A sparse, random distribution of
      fine-caliber profiles from deep vibrissal nerves was labeled at the level of the
      cavernous sinus in the deep half of the F-SCs. GSA I-B4 also labeled a variety of
      nonneural structures. By binding to vascular linings, GSA I-B4 revealed a dense,
      highly organized capillary system within the mesenchymal sheath that forms the
      inner lining of the vascular sinuses. Thus each F-SC appears to have a closed
      capillary system within the open vascular sinus. Trabeculae within the lumen of
      the cavernous sinus were also revealed to span between the sinus capsule and the
      mesenchymal sheath only about midway along the length of the follicle instead of
      the entire deeper half, as was previously believed. in addition, GSA I-B4 bound
      to the surface of follicular cells preferentially in the superficial half of the
      F-SCs. Sweat glands within the intervibrissal fur and some cells within sebaceous
      glands in F-SCs were also labeled as well as their ducts. The potential
      functional implications of these various features are discussed.

PMID- 8282850
TI  - Taste and tactile responsiveness of neurons in the posterior diencephalon of the
      channel catfish.
AB  - Many teleosts possess an enlargement of the ventral diencephalon called the
      inferior lobe. In ostariophysine species (e.g., carps and catfishes), this region
      receives ascending fibers from the primary and secondary gustatory centers in the
      hindbrain. Extracellular unit activity was recorded from identified nuclei in the
      inferior lobe of the channel catfish to characterize taste and tactile
      responsiveness from the different nuclei associated with gustatory projections.
      Taste responses (to amino acids and nucleotides) were recorded from units in the
      nucleus centralis (nCLI), nucleus lobobulbaris (caudal portion--nLB,
      rostrolateral portion--rl nLB, and parvicellular portion--nLBp), and lateral
      thalamic nucleus (nLT), supporting the proposed gustatory role for these nuclei.
      Tactile responsiveness was distinct between different nuclei in the caudal
      inferior lobe. Units from the nCLI and nLB had lower spontaneous activity than
      those from other nuclei, and typically had receptive fields including the whole
      extraoral body surface, ipsilaterally. Units from the rl nLB and nLBp had
      receptive fields, often including both oral and extraoral surfaces, bilaterally,
      but rl nLB receptive fields typically included the whole body, while those from
      nLBp units were often restricted to the head and mouth. The apparent
      electrophysiological distinction between these nuclei, combined with their
      different connectivity patterns, suggest that the gustatory nuclei in the
      inferior lobe of channel catfish are involved in various different sensory
      processing mechanisms.

PMID- 8282851
TI  - An immunocytochemical study of the FMRFamide neuropeptide gene products in
      Drosophila.
AB  - We have mapped protein expression of the FMRFamide neuropeptide gene in
      Drosophila with polyclonal antisera against three small peptides whose sequences
      were derived from the Drosophila proFMRFamide precursor. One antiserum was
      affinity-purified and extensively characterized. The enriched antibodies labeled
      15-21 bilaterally symmetric pairs of neurons in a pattern that corresponded very
      closely to the pattern of in situ hybridization that was determined previously
      (Schneider et al. [1991] J. Comp. Neurol. 304:608-622; O'Brien et al. [1991] J.
      Comp. Neurol. 304:623-638). The other antisera produced complementary results.
      These findings suggest that the antisera specifically label cells that express
      the FMRFamide gene. In larvae we consistently observed strong staining in
      identified interneurons and neuroendocrine cells, and moderate to weak staining
      in neurons of unknown function. The adult pattern of expression included both
      larval neurons whose immunoreactivity persisted through metamorphosis and adult
      specific neurons. During metamorphosis, we observed transient staining in a small
      number of neurons and in specific neuropil regions that included the central
      body, the protocerebral bridge, and the optic ganglia. Based on these
      morphological features, we suggest that the FMRFamide-like neuropeptides in
      Drosophila play a number of functional roles, perhaps affecting both
      physiological and developmental phenomena. Such roles include general modulation
      throughout all post-embryonic stages, via the blood, and also more stage- and
      region-specific modulation within the CNS.

PMID- 8282852
TI  - Distribution of GABAergic synaptic terminals on the dendrites of locust spiking
      local interneurones.
AB  - Double-labelling and electron microscopy were used to assess the distribution of
      GABAergic synapses made onto the neurites of spiking local interneurones in the
      locust. The aims were to determine the sites of inputs mediating inhibition of
      the spiking local interneurones and to ascertain the relative abundance of such
      inputs. This information should allow us to understand better the integrative
      properties of these spiking local interneurones and the role of inhibition in
      shaping their receptive field properties or in fine tuning their spike-mediated
      outputs. Spiking interneurones in a midline population were labelled by
      intracellular injection of horseradish peroxidase after physiological
      characterisation. Colloidal gold immunocytochemistry was then used on ultrathin
      sections of these neurones with a polyclonal antibody raised against GABA. Most
      GABAergic (inhibitory) input synapses onto the interneurones are made on their
      ventral neurites, which also receive afferent (excitatory) inputs. These
      inhibitory inputs to the ventral neurites constitute 43% of the identifiable
      synapses. Relatively few GABAergic inputs were found onto the dorsal neurites,
      which are predominantly the sites of output synapses from these interneurones.
      These results suggest that much synaptic integration takes place in the ventral
      field of branches and that GABA-mediated presynaptic inhibitory control of spike
      mediated outputs from the dorsal neurites is unlikely to occur.

PMID- 8282853
TI  - SmI cortical barrels in an Australian marsupial, Trichosurus vulpecula (brush
      tailed possum): structural organization, patterned distribution, and somatotopic
      relationships.
AB  - This study reports on the cerebral cortex of an Australian marsupial, Trichosurus
      vulpecula (brush-tailed possum). It consists of an analysis of layer IV of
      somatosensory cortex in tangential sections of flattened specimens and in oblique
      radial sections stained to show Nissl substance or myelin, or tested for succinic
      dehydrogenase. It includes results of electrophysiological mapping experiments
      that ascertained the somatotopic significance of the cytoarchitecture of this
      cortical region. Layer IV has two interlocking cytoarchitectural fields: one
      granular (the barrelfield, comprising cell-dense barrels 150 to 500 microns in
      diameter) and one dysgranular. Only neurons within the granular field responded
      to light cutaneous stimulation. In the barrelfield cell-sparse septa (about 100
      microns wide), low in succinic dehydrogenase activity and containing many radial
      myelinated axons, separate adjoining barrels. Possum barrels are "solid," lacking
      the prominent hollows characteristic of most rodent barrels. In some specimens
      three to five small neuronal "lobules" may constitute each large barrel. In
      tangential sections the size, shape, and arrangement of barrels combine to form a
      histological caricature of the possum's body, especially of the face and forepaw.
      Six rows of "mystacial barrels" are homeomorphic to the six rows of large
      mystacial vibrissae, and "forepaw barrels" are homeomorphic to the glabrous
      palmar and apical digital pads. Correlating cortical recording sites and
      receptive fields confirmed that individual barrels represent specific cutaneous
      regions. These results show that the cortical barrels of brush-tailed possums are
      remarkably similar to those of rodents, in structure, arrangement, and functional
      significance.

PMID- 8282854
TI  - Distribution of the inositol 1,4,5-trisphosphate receptor, P400, in adult rat
      brain.
AB  - The distribution of the inositol 1,4,5-trisphosphate receptor protein, P400, was
      investigated in adult rat brain by immunocytochemistry with the monoclonal
      antibody 4C11 raised against mouse cerebellar inositol 1,4,5-trisphosphate
      receptor protein. Immunoreactive neuronal cell bodies were detected in the
      cerebral cortex, the claustrum, the endopiriform nucleus, the corpus callosum,
      the anterior olfactory nuclei, the olfactory tubercle, the nucleus accumbens, the
      lateral septum, the bed nucleus of the stria terminalis, the hippocampal
      formation, the dentate gyrus, the caudate-putamen, the fundus striatum, the
      amygdaloid complex, the thalamus, the caudolateral part of the hypothalamus, the
      supramammillary nuclei, the substantia nigra, the pedunculopontine tegmental
      nucleus, the ventrotegmental area, the Purkinje cells in the cerebellum, the
      dorsal cochlear nucleus, the subnucleus oralis and caudalis of trigeminal nerve,
      and the dorsal horn of the spinal cord. Immunoreactive fibres were found in the
      medial forebrain bundle, the globus pallidus, the stria terminalis, the pyramidal
      tract, the spinal tract of trigeminal nerve, and the ventral horn of spinal cord.
      Nerve fibres forming a dense plexus ending in terminal-like boutons were detected
      in relation to nonimmunoreactive neurons of the dentate, interpositus, and
      fastigial nuclei of the cerebellum and around neurons of the vestibular nuclei.
      This receptor protein binds a specific second messenger, inositol 1,4,5
      trisphosphate, which produces a mobilization of intracellular Ca2+ and a
      modulation of transmitter release.

PMID- 8282855
TI  - Morphology of interneurones in pathways from group II muscle afferents in sacral
      segments of the cat spinal cord.
AB  - The morphology of 12 sacral interneurones with peripheral input from group II
      muscle afferents was analyzed after intracellular injection of horseradish
      peroxidase (HRP). The neurones were located in Rexed's laminae III-V overlying
      the pudendal (Onuf's) motor nucleus. The interneurones had medium sized elongated
      somata and dendrites projecting radially. All of the interneurones were funicular
      neurones and fell into two categories depending on whether their axons ran within
      the dorsal part of the lateral funiculus (DLF; n = 7) or within the ventral
      funiculus, or the ventral part of the lateral funiculus (VF or VLF; n = 4). The
      latter were located more rostrally. Within the DLF similar proportions of stem
      axons and secondary axonal branches descended and ascended. Within the VF and VLF
      all of the axons ascended. Collaterals of axons running in the DLF arborized
      primarily within the dorsal horn and the intermediate zone; none were found to
      approach the motor nuclei. In contrast, collaterals of axons running in the
      VF/VLF arborized in both the intermediate zone and the ventral horn and passed
      close to the motor nuclei. We conclude that sacral interneurones with group II
      input are morphologically nonhomogenous and that only those located most
      rostrally might have direct actions upon motoneurones. Both the axonal
      projections and the input (from group II but not from group I muscle afferents
      and from skin afferents) of sacral interneurones indicate that they are
      homologous to dorsal horn group II interneurones in the midlumbar segments. They
      appear, however, to form part of more local neuronal networks than their
      midlumbar counterparts.

PMID- 8282856
TI  - MRI in chronic progressive radiation myelopathy.
AB  - OBJECTIVE: Our goal was to assess medullary lesions in patients suffering from
      chronic progressive radiation myelopathy (CPRM) using MRI. MATERIALS AND METHODS:
      In a group of 10 patients suffering from CPRM, MRI findings (11 examinations),
      radiation protocols, and patient prognoses were reviewed. RESULTS: A cord
      enlargement was demonstrated in five cases, whereas four cases presented with
      medullary atrophy. As demonstrated by MRI, radiation-induced medullary lesions
      progressed toward cord atrophy in one patient. When MRI and/or comparison
      myelogram were performed within 8 months following the onset of the myelopathy, a
      cord enlargement was usually encountered. When the patient was evaluated > 8
      months after the first neurological symptoms, a cord atrophy was always
      demonstrated. Medullary lesions extended beyond the boundaries of the radiation
      field in 67% of the cases. However, with the exception of one case, the main
      focus of the cord damage was included within an irradiated cord segment. An
      enlarged cord was often associated with a neurologic deterioration and a fatal
      outcome. In patients with cord atrophy, the neurologic deficit was often static
      and survival rates were better. CONCLUSION: These results suggest a revision of
      classic criteria used for the diagnosis of CPRM. By demonstrating cord lesions,
      MRI helps to establish disease prognosis.

PMID- 8282857
TI  - Myocardial [18F]FDG tomography using a conventional gamma camera and a seven
      pinhole collimator.
AB  - OBJECTIVE: Seven pinhole tomography (SPHT) is fast, inexpensive, and, because it
      relies on standard gamma cameras and computers, available everywhere. This
      article investigates the suitability of SPHT for the detection and localization
      of 511 keV gammas emitted from 18F without coincidence detection. MATERIALS AND
      METHODS: A standard SPH collimator and the table were additionally shielded with
      lead. For comparison, point sources and cardiac phantoms were imaged on SPHT and
      a triple head gamma camera (THC). The phantom studies were supplemented with
      patient examinations using a standard clinical protocol. Circumferential profiles
      allowed a direct comparison of perfusion under different conditions or perfusion
      plus metabolism. RESULTS: Dedicated for cardiac workup, SPHT has a 5-10 times
      better sensitivity (dependent on distance) than THC and gives superior resolution
      for the extension of a lesion perpendicular to the long cardiac axis: The full
      width at half-maximum for x- and y-directions (FWHMx,y) for a 99mTc-point source
      was found to be 35 and 22% smaller at 130 and 220 mm distances with SPHT than
      with THC. The SPHT even surpasses the THC at greater distances. The resolution
      falls off with 18F: FWHM increases by 70 and 48%, respectively, compared to
      99mTc. The in-depth resolution is worse with SPHT: The FWHM (using 99mTc) is 2
      3.5 times greater with SPHT than with THC and remains within this range with 18F.
      CONCLUSION: It is possible to image 18F distributions using SPHT with a very high
      sensitivity and good detail resolution, even in the presence of 99mTc and 201Tl.
      The SPHT compares well with THC for 99mTc, except in its in-depth resolution, and
      is unsurpassed in its sensitivity and ease of performance.

PMID- 8282858
TI  - The ECAT EXACT HR: performance of a new high resolution positron scanner.
AB  - OBJECTIVE: The ECAT EXACT HR is a newly designed CTI-Siemens PET scanner with
      high spatial resolution. Its physical performance with respect to resolution,
      count rate efficiency, and scatter was investigated and evaluated with phantom
      studies. MATERIALS AND METHODS: The new tomograph consists of three rings of 112
      BGO block detectors (50 mm x 23 mm x 30 mm deep) each, covering an axial field of
      view of 15 cm with a patient port of 56 cm diameter. Each block is sawed into an
      8 x 7 matrix giving 24 detector rings with 784 crystals each. RESULTS: Total
      sensitivity for a 20 cm cylinder phantom is 177 kcps/microCi/ml in two
      dimensional (2D) mode and increases to 1.46 Mcps/microCi/ml in 3D mode. Count
      rate performance was investigated for different low energy discriminator
      thresholds. Smaller detector blocks improve noise equivalent counts by
      approximately 50% compared with the EXACT system both in 2D and in 3D mode.
      Scatter fractions vary in 2D from 0.09 to 0.13 for energy thresholds from 450 to
      250 keV for line sources in a 20 cm diameter phantom. In 3D mode an increase of
      scatter by a factor of 3 is observed. Transaxial spatial resolution varies from
      3.6 mm full width at half-maximal (FWHM) at the center to 4.5 mm FWHM
      tangentially and 7.4 mm FWHM radially at R = 20 cm. Average axial resolution
      changes from 4.0 mm FWHM at center to 6.7 mm FWHM at R = 20 cm. CONCLUSION: Due
      to its special properties, the EXACT HR can be equally applied to routine
      clinical brain and whole-body imaging and to noninvasive experimental studies of
      regional tracer concentrations in medium-sized animals.

PMID- 8282859
TI  - Effect of water fraction in selection of optimal TI value for STIR sequences.
AB  - OBJECTIVE: This article describes the effect of the water fraction in the
      selection of the optimal TI value in a STIR sequence. This effect has been given
      little consideration in previous studies. MATERIALS AND METHODS: Therefore, using
      both STIR combined with the Dixon method (opposed-phase STIR) and conventional
      STIR (in-phase STIR), we have investigated the effect of the water fraction in
      the selection of an optimal TI value for the STIR sequence. RESULTS: Our findings
      have indicated that the water protons rather than the olefinic protons (-CH = CH
      ) play a major role in the opposed-phase effect in vivo. CONCLUSION: Thus, it has
      been concluded that the most effective fat suppression can be achieved when the
      intravoxel phase cancellation effect between the water and lipid protons is
      maximal, rather than when the longitudinal magnetization of the lipid protons is
      minimal.

PMID- 8282860
TI  - Enhanced detection of brain tumors by [18F]fluorodeoxyglucose PET with glucose
      loading.
AB  - OBJECTIVE: We applied glucose loading during PET studies with [18F]2-fluoro-2
      deoxy-D-glucose (FDG) to enhance detection of brain tumors by diminution of FDG
      uptake in normal gray matter. MATERIALS AND METHODS: This study involved three
      patients with glioblastomas. Two PET scans were performed in all cases within 1
      week in control and with glucose loading state. RESULTS: In all patients, tumor
      was depicted more clearly with glucose loading than in the control study. The FDG
      uptake ratio of tumor to normal cortical gray matter showed a mean increase of
      27% with glucose loading. CONCLUSION: This technique might be useful for
      detection of recurrent or residual tumors.

PMID- 8282861
TI  - Acute purulent leptomeningitis mimicking subarachnoid hemorrhage on CT.

PMID- 8282862
TI  - Subependymoma of filum terminale: MR appearance.
AB  - This report describes a subependymoma of the filum terminale evaluated by MRI.
      The mass demonstrated hyperintense signal on conventional spin echo T1-weighted,
      proton density, and T2-weighted imaging and nonenhancement after intravenous
      gadolinium administration. These characteristics distinguish this lesion from
      other more common neoplastic and inflammatory lesions arising in the lumbar
      spinal canal that are typically isointense on T1-weighted spin echo acquisitions,
      hyperintense on T2-weighted imaging, and enhance variably after intravenous
      gadolinium administration.

PMID- 8282863
TI  - MR appearance of intraocular silicone oil.
AB  - A 41-year-old man with AIDS and cytomegalovirus retinitis with retinal detachment
      was studied with CT and MR. Part of his treatment had been a vitrectomy with
      intravitreal injection of silicone oil as an attempt to stop further retinal
      detachment. This form of therapy is being used more frequently and radiologists
      should be familiar with the imaging appearance of such deposits of silicone oil.
      In this case the oil was hyperdense to muscle on CT and had a homogeneous
      intermediate signal intensity on all pulse sequences on MRI.

PMID- 8282864
TI  - Postcontrast CT in the diagnosis and assessment of response to thrombolysis in
      massive pulmonary embolism.
AB  - We present a case of massive acute pulmonary embolism where contrast enhanced
      helical CT was compared with standard angiography for diagnosis and for
      monitoring subsequent response to thrombolytic therapy. There was very close
      concordance of the findings on these modalities suggesting that contrast enhanced
      helical CT may be an easy and reliable alternative to standard angiography.

PMID- 8282865
TI  - Use of cine gradient echo (GRE) MR in the imaging of cardiac hemochromatosis.
AB  - This case report describes the MR appearance of cardiac iron deposition using
      spin echo and cine gradient echo imaging (GRE) in a young man with secondary
      hemochromatosis. The ratio of the signal intensity of left ventricular myocardium
      to skeletal muscle was abnormally low on both spin echo and GRE compared with
      normal. The abnormally low myocardial signal was most severe on the cine gradient
      echo sequence. Cine GRE can be used to establish the diagnosis of cardiac iron
      deposition.

PMID- 8282866
TI  - Hyperacute rejection in liver transplantation: CT findings.
AB  - Hyperacute rejection is rare after liver transplantation. We report a case of
      early graft failure following liver transplantation in a 46-year-old woman. On
      the 5th postoperative day, progressive loss of graft function occurred. Liver
      histology showed submassive hepatic necrosis. Computed tomography features
      showing large geographic areas of necrosis without anatomic distribution were
      suggestive of hyperacute rejection.

PMID- 8282867
TI  - MR demonstration of reversible periportal abnormal intensity in eclampsia.
AB  - We present a patient with toxemia of pregnancy and liver dysfunction. Magnetic
      resonance imaging revealed diffuse periportal abnormal signal intensity in the
      liver, which resolved as the liver enzyme levels returned to normal values.

PMID- 8282868
TI  - CT of microcystic (serous) pancreatic adenoma.
AB  - Although microcystic adenoma of the pancreas is well recognised as a benign
      tumour, it is often treated surgically. We present serial CT over 9 years of a
      patient with this tumour that demonstrated a substantial rate of growth and the
      development of pathognomonic features.

PMID- 8282869
TI  - CT of abdominal barium intravasation.
AB  - We report a case of barium intravasation due to misplacement of the catheter tip
      during a barium enema examination, leading to vaginal laceration and barium
      sequestration within the reticuloendothelial system of a 57-year-old woman who
      survived this potentially fatal event. The radiologic appearance on CT,
      sonography, MR, and plain radiography is presented. Computed tomography
      demonstrated barium sequestered by the liver, spleen, and renal cortex. The
      portal veins were seen as branching radiolucent densities superimposed on a dense
      parenchymal background.

PMID- 8282870
TI  - Monoamniotic twins discordant for anencephaly: diagnosis by CT amniography.
AB  - Prenatal diagnosis of monoamnionicity is necessary for optimal care of a twin
      gestation. When the fetuses are discordant for a lethal anomaly, unequivocal
      confirmation is imperative. Ultrasound evaluation of our patient revealed a twin
      gestation discordant for anencephaly and with possible monoamnionicity. When
      sonography was inconclusive, CT amniography confirmed a single amniotic cavity,
      permitting appropriate parental counseling and pregnancy management. CT
      amniography is a useful adjunct to ultrasound in evaluating twins discordant for
      a lethal anomaly when monoamnionicity is suspected.

PMID- 8282871
TI  - MRI of transient postencephalitic parkinsonism.

PMID- 8282872
TI  - Two leiomyomas of the liver in an adult with AIDS: CT and MR appearance.

PMID- 8282873
TI  - Periportal fibrosis in Langerhans' cell histiocytosis mimicking multiple liver
      tumors: US, CT, and MR findings.

PMID- 8282874
TI  - MRI of esthesioneuroblastoma.
AB  - OBJECTIVE: Esthesioneuroblastomas are uncommon tumors originating in the
      olfactory epithelium of the superior nasal cavity. Accurate staging appropriately
      guides therapy and predicts survival. The MR appearance and pattern of contrast
      enhancement in these tumors have not been well described. The goals of this
      article were to analyze the MRI characteristics of esthesioneuroblastoma,
      including extent of tumor, differentiation from obstructive sinus disease, MR
      signal, and pattern of contrast enhancement. MATERIALS AND METHODS: The MR
      examinations of six patients with proven advanced esthesioneuroblastoma were
      reviewed. Standard SE T1- and T2-weighted axial images were obtained [550-600/15
      25 and 2,000-2,760/80-90 (TR/TE), respectively], followed by postcontrast axial
      and coronal T1-weighted sequences in all patients. RESULTS: Five of the six
      tumors were centered in the superior nasal cavity and one was centered in the
      lateral ethmoid air cells. Five tumors extended intracranially. Postobstructive
      sinus disease was always encountered. As compared to gray matter, the signal on
      T1-weighted images was either hypo- or isointense. On T2-weighted images, the
      signal varied from iso- to hyperintensity. Contrast enhancement was intense and
      of variable uniformity. CONCLUSION: Magnetic resonance signal characteristics
      helped to distinguish obstructive sinus disease from tumor. The MR signal
      characteristics and pattern of contrast enhancement were nonspecific for
      esthesioneuroblastoma. Enhanced images, particularly in the coronal plane, were
      very helpful in identifying intracranial extension.

PMID- 8282875
TI  - Oblique sagittal MRI of anterior cruciate ligament.

PMID- 8282876
TI  - CT-guided percutaneous insertion of interstitial radiotherapy catheters in head
      and neck tumors.
AB  - We describe a new method of placing interstitial radiation therapy catheters in
      patients with head and neck tumors. In three patients with recurrent inoperable
      head and neck tumors CT guidance was utilized to insert interstitial radiation
      therapy catheters percutaneously. This method enabled palliative radiation
      therapy to be administered without the need for surgical placement of seeds or
      catheters. The detailed anatomical localization of tumor and vascular structures
      provided by CT enabled precise percutaneous placement of afterloading catheters
      while ensuring safety. Pain was reduced and tumor size was decreased in all three
      patients. The CT-guided percutaneous insertion of afterloading catheters is a
      simple yet effective method of providing interstitial radiation therapy for head
      and neck tumors.

PMID- 8282877
TI  - CT of cystic jaw lesions.
AB  - OBJECTIVE: Our goal was to compare the efficacy of CT with that of plain film
      radiography (PFR) in analyzing the three-dimensional shape and structure of
      cystic jaw lesions. MATERIALS AND METHODS: Twenty patients with cystic lesion of
      the jaw were studied by PFR and CT. The three-dimensional outline of the cyst and
      the distances between the cyst wall and adjacent vital teeth, cortical jaw bone,
      maxillary sinus, and mandibular canal were estimated on PFR and on CT scans.
      RESULTS: Computed tomography was superior to PFR in the demonstration of the
      three-dimensional bony margins of the cyst and in determination of its proximity
      to adjacent vital structures (p < 0.01, sign test). CONCLUSION: Application of CT
      is useful for diagnosis and treatment planning of cystic lesions of the jaws.

PMID- 8282878
TI  - Enhancement of thoracic masses using nonionic MR contrast agents.
AB  - OBJECTIVE: This study evaluated the effect of a new nonionic MR contrast medium,
      gadodiamide injection (Omniscan; Sanofi-Winthrop), on enhancement of thoracic
      masses on T1-weighted SE images. MATERIALS AND METHODS: Gadodiamide injection was
      administered intravenously at a dose of 0.2 mmol/kg to 26 patients with thoracic
      masses. The T1-weighted images with and without fat suppression and T2-weighted
      images obtained before contrast medium injection were compared with T1-weighted
      images obtained at 5, 30, and 45 min and a T1-weighted fat-suppressed image at 10
      min after administration of the contrast medium. Enhancement of the thoracic
      masses and image quality were quantified by measuring signal intensity, signal-to
      noise ratio (SNR), and contrast-to-noise ratio (CNR) using muscle and fat as
      reference tissues. RESULTS: The SNR of the masses increased significantly (p <
      0.001) following contrast material injection both on standard T1-weighted
      sequences and on T1-weighted fat-suppressed images when compared with the
      precontrast T1-weighted images with and without fat suppression. The CNR
      (reference tissue muscle) improved significantly (p < 0.001) after contrast
      medium injection and persisted for 45 min on T1-weighted images compared with
      those prior to contrast medium. However, there was no significant difference in
      CNR between the T2-weighted images obtained before and the T1-weighted images
      obtained after contrast agent administration. On the other hand, the SNR of
      contrast-enhanced images was significantly better than that of the T2-weighted
      images. When fat was used as a reference tissue, CNR of the thoracic masses
      decreased significantly. CONCLUSION: This study shows that gadodiamide injection
      caused significant enhancement of thoracic masses on T1-weighted images, which
      rendered high signal intensity to the masses similar to the appearance on T2
      weighted images. In comparison with the T2-weighted images, SNR was significantly
      improved.

PMID- 8282879
TI  - Sclerosing hemangiomas of the lung and interlobar fissures: CT findings.
AB  - OBJECTIVE: Sclerosing hemangioma is a rare pulmonary tumor. This article
      describes CT features of the tumor on the basis of CT-pathology correlation.
      MATERIALS AND METHODS: The CT features of eight patients with sclerosing
      hemangioma of the lung were studied retrospectively and were correlated with the
      pathologic findings of the resected specimens. All eight patients had an
      incidental lung mass found on chest radiographs. Seven patients were female.
      Contrast enhancement of the masses was assessed visually by two radiologists
      independently, and the density was measured before and after contrast enhancement
      by using a standard cursor in three patients. RESULTS: On CT, sclerosing
      hemangiomas appeared as well defined juxtapleural masses in all cases. The tumors
      enhanced by visual criteria in all but one patient with the smallest mass. The CT
      density of the enhancing mass ranged from 96 to 157 HU. Three patients had
      calcification and two had well defined areas of low attenuation. On CT-pathology
      correlation, the higher, iso-, and lower attenuation areas corresponded with
      angiomatous, solid and sclerotic, and cystic areas, respectively. CONCLUSION: A
      well defined juxtapleural mass with marked contrast enhancement coupled in select
      cases with foci of sharply marginated areas of low attenuation and calcification
      are characteristic CT findings of sclerosing hemangioma and should suggest this
      diagnosis especially in women with these findings.

PMID- 8282880
TI  - MRI of tracheal and esophageal compression following surgery for congenital heart
      disease.
AB  - OBJECTIVE: Magnetic resonance imaging has proven to be a useful diagnostic tool
      for the evaluation of various types of vascular rings and congenital heart
      disease. We report two cases showing the accuracy of MRI in detecting post
      surgical complications in patients with these conditions. MATERIALS AND METHODS:
      The two cases reported here demonstrate the use of MRI to show the altered
      vascular anatomy and the mechanism of tracheal and/or esophageal compression.
      RESULTS: In the first case, MRI demonstrated narrowing of the right pulmonary
      artery due to a dilated and posteriorly displaced ascending aorta with residual
      coarctation, and esophageal compression by an aberrant left subclavian artery. In
      the second case, MRI demonstrated esophageal compression by a posteriorly
      displaced ascending aorta. CONCLUSION: We conclude that MRI is an effective
      noninvasive method for assessing the results and complications of surgical
      correction of aortic abnormalities.

PMID- 8282881
TI  - Mediastinal Castleman disease: CT findings.
AB  - OBJECTIVE: Our objective was to characterize the CT findings of mediastinal
      Castleman disease. MATERIALS AND METHODS: We reviewed the CT findings of
      mediastinal Castleman disease in 10 patients. RESULTS: In nine cases of hyaline
      vascular type Castleman disease, lymph nodes were 2-7 cm in diameter and located
      in the hilum in six patients, superior mediastinum in two patients, and posterior
      mediastinum in one patient. On CT the tumors were well-demarcated round masses
      showing dense homogeneous enhancement after contrast medium injection. Dynamic CT
      in one case showed gradual centripetal enhancement of the mass. In one case of
      hyaline-vascular type Castleman disease, lumpy and irregular calcifications were
      noted in the center of the mass. In the one case of plasma cell type Castleman
      disease, multiple small homogeneously enhancing nodes were found in the
      mediastinal and supraclavicular area. CONCLUSION: CT findings may suggest the
      preoperative diagnosis of mediastinal Castleman disease.

PMID- 8282882
TI  - Lymphoproliferative disorder involving the liver following transplantation: CT
      appearance.
AB  - OBJECTIVE: Our goal is to report the CT findings of liver involvement in
      lymphoproliferative disease in immunosuppressed patients. MATERIALS AND METHODS:
      We report CT findings in two cases of lymphoproliferative disease involving the
      liver. RESULTS: The findings of this disorder are nonspecific both clinically and
      radiographically. CONCLUSION: Nonspecific nodular pattern in the liver on CT may
      represent unrestricted lymphocytic infiltration in the immunosuppressed patient.

PMID- 8282883
TI  - 3DFT-FISP MRI with gadopentetate dimeglumine in differential diagnosis of small
      liver tumors.
AB  - OBJECTIVE: We assessed the value of dynamic sequential three-dimensional Fourier
      transformation (3DFT) MRI in differentiating various types of small liver tumors.
      MATERIALS AND METHODS: Forty-seven patients with 65 liver masses < 3 cm in size
      (42 hepatocellular carcinomas, 11 hemangiomas, 12 metastatic tumors) were studied
      by 3DFT fast imaging with steady-state precession (FISP) MRI [TR(ms)/TE(ms)/flip
      angle (degree): 20/8/30]. The slab thickness was 21-35 mm, and there were seven
      partitions. The 3DFT-FISP MR images were obtained immediately after 0.1 mmol/kg
      of gadopentetate dimeglumine was administered intravenously over 2-3 s (early
      phase), 60 s after (late phase I), and 120 s after (late phase II). RESULTS:
      Eighty-six percent of small hepatocellular carcinomas showed hyperintense
      enhancement relative to the surrounding liver parenchyma and iso- or hypointense
      enhancement with or without capsular enhancement in the late phase. Eighty-two
      percent of small hemangiomas showed peripheral globular enhancement in the early
      phase and total hyperintense or peripheral enhancement in the late phases. Ninety
      two percent of the small metastatic liver tumors showed doughnut-like ring
      enhancement in the early phase. CONCLUSION: By dynamic 3DFT-FISP MRI, we were
      able to accurately evaluate the hemodynamics and morphological findings of each
      type of small liver tumor.

PMID- 8282884
TI  - Portocaval shunt with unusual CT and MR manifestations.
AB  - OBJECTIVE: We investigated the radiological findings of three cases with unusual
      portocaval shunts. MATERIALS AND METHODS: Three patients with liver cirrhosis and
      portal hypertension were examined using CT and MRI. CT was performed using
      intravenous bolus injection of contrast medium in one and with incremental
      dynamic scanning in two cases. MRI was performed with a 1.5 or 0.5 T
      superconducting system or with a 0.22 T resistive system in the three patients.
      RESULTS: CT and MRI showed tortuous intrahepatic tubular structures connecting
      the right posterior portal vein to the inferior vena cava (IVC) in two of the
      patients. An anomalous vein arising from the extrahepatic portal vein was a
      tributary connected with the IVC in one patient. Symptoms associated with hepatic
      encephalopathy were present in two of the patients whose blood ammonia levels
      were elevated. CONCLUSION: The possibility of the existence of hepatic
      encephalopathy should be borne in mind when these shunts are detected during
      abdominal imaging.

PMID- 8282885
TI  - CT attenuation values and enhancing characteristics of thoracoabdominal
      lymphomatous adenopathies.
AB  - OBJECTIVE: Thoracoabdominal lymphomatous adenopathies have been described as
      homogeneous and typically showing little enhancement on postcontrast CT. After
      observing pronounced adenopathic contrast enhancement in one patient with
      lymphoma, we prospectively investigated the CT enhancing characteristics and
      attenuation values of pathologic thoracic and abdominal lymph nodes in 25
      patients with lymphoma. MATERIALS AND METHODS: Unenhanced CT of the chest,
      abdomen and pelvis was performed in all cases. The enhancing characteristics and
      attenuation values of the largest node or group of nodes were evaluated at 1, 2,
      5, and 10 min after a 100 ml intravenous bolus injection of contrast medium.
      RESULTS: On unenhanced CT the nodes were of soft-tissue attenuation (42 +/- 5 HU)
      in 23 cases and of low attenuation (31 and 28 HU) in 2 cases. The maximum
      enhancement was achieved at 1 or 2 min postinjection and was low (16 +/- 6 HU) or
      moderate (31 +/- 6 HU) in 21 cases and pronounced (61 +/- 5 HU) in 4. The
      patterns of enhancement were classified as homogeneous (no. = 23) inhomogeneous
      (no. = 1), and peripheral (no. = 1). CONCLUSION: Thoracic and abdominal
      lymphomatous adenopathies are usually of soft-tissue attenuation on unenhanced CT
      and can show slight, moderate, or even pronounced enhancement on postcontrast CT.

PMID- 8282886
TI  - Abdominal iron distribution in sickle cell disease: MR findings in transfusion
      and nontransfusion dependent patients.
AB  - OBJECTIVE: Our goal was to determine the difference in iron distribution between
      transfusion dependent (TD) and nontransfusion dependent (NT) patients with sickle
      cell disease (SCD). MATERIALS AND METHODS: The T2-weighted and T2*-weighted
      abdominal MR images in nine cases of homozygous SCD were reviewed to determine
      the distribution of low signal from iron in five TD and four NT patients.
      RESULTS: All eight patients with visualized spleens had decreased splenic signal
      intensity. One patient who had no history of splenectomy had no visualized
      splenic tissue. The majority of both groups had renal cortex of low signal
      intensity that was attributable to iron deposition from intravascular hemolysis
      and was not correlated with clinical renal abnormalities. None of the NT group
      had liver or pancreas of low signal intensity, while all five TD patients had
      decreased liver signal intensity and three of five had decreased pancreatic
      signal intensity. CONCLUSION: Decreased pancreatic signal intensity can occur in
      TD patients, perhaps suggesting total body iron overload. Nontransfusion
      dependent sickle cell patients usually have normal hepatic signal intensity and
      do not have total body iron overload, even in the presence of renal and splenic
      iron deposition.

PMID- 8282887
TI  - MR diagnosis of haemorrhagic cystic renal cell carcinoma.
AB  - OBJECTIVE: We report two cases of cystic renal masses considered indeterminate on
      sonography and CT, in which haemorrhagic contents were demonstrated on MRI.
      MATERIALS AND METHODS: Spin echo T1-weighted axial and coronal (TR 700 ms; TE 17
      ms) and T2-weighted axial (TR 3,000 ms; TE 90 ms) upper abdominal scans were
      obtained on a 1.5 T MR machine. RESULTS: Cyst contents were of high signal on
      both T1- and T2-weighted sequences, indicating internal haemorrhage, which was
      confirmed at surgery. CONCLUSION: There is a high propensity for haemorrhagic
      renal masses to mask carcinoma. By distinguishing blood from other contents, MRI
      had a noninvasive role in diagnosis and further management.

PMID- 8282889
TI  - CT appearance of pediatric ovaries and uterus.
AB  - OBJECTIVE: The purpose of this study was to evaluate the changes in pediatric
      uterine and ovarian morphology with age. MATERIALS AND METHODS: The CT scans of
      125 young girls and adolescents between 1 and 18 years of age without clinical
      evidence of gynecological abnormality were retrospectively studied. The uterus
      and ovaries, respectively, were visualized in 66 and 6.3% of girls under 8 years
      of age vs. 92 and 75% of girls over 8 years of age. RESULTS: Mean ovarian volume
      was < or = 0.8 cm3 in girls under 8 years of age and between 2.1 and 6.9 cm3 in
      older girls. Cysts were seen in > 70% of all girls, regardless of age. Mean
      uterine volume ranged between 0.5 and 1.3 cm3 in girls under 8 years of age and
      between 4.1 and 37.3 cm3 in older girls. The CT diagnosis of pelvic organ
      pathology could nearly always be made on the basis of altered morphology, but
      size criteria were helpful when morphology was not significantly altered.
      CONCLUSION: Our study shows that ovaries are not well seen on CT in girls 8 years
      of age and younger. When ovaries are visualized, cysts are a common finding in
      healthy young and adolescent girls. The uterus is visualized more easily at all
      ages.

PMID- 8282888
TI  - MRI of AIDS-related polyradiculomyelitis.
AB  - OBJECTIVE: We describe the unusual syndrome of cytomegalovirus (CMV)
      polyradiculomyelitis and its MR findings in two patients with AIDS. MATERIALS AND
      METHODS: The clinical records and MRI studies of two patients with AIDS and CMV
      polyradiculomyelitis were reviewed. The MR images were performed on a Picker 1.0
      or 1.5 T MR unit. Axial and sagittal T1-weighted images of the lumbar spine were
      obtained, pre- and post-Gd-DTPA (0.1 mmol/kg) administration. Gradient echo
      sagittal images were also obtained. RESULTS: Precontrast images demonstrated a
      thickened cauda equina in both patients. In one patient the conus was ill defined
      on precontrast images. Post-contrast images demonstrated diffuse enhancement of
      the cauda equina in both patients as well as enhancement along the surface of the
      conus. In one patient the nerve roots were clumped and adherent to the walls of
      the thecal sac as well as to other nerve roots. CONCLUSION: The clinical
      presentation of urinary retention, flaccid paraparesis, back and/or leg pain, and
      "saddle anesthesia" in a patient with AIDS should suggest the diagnosis of CMV
      polyradiculomyelitis. Although diffuse enhancement of the cauda equina on
      postcontrast MRI is a nonspecific finding, it would strongly support this
      diagnosis in the appropriate clinical setting. The diagnosis may be easily missed
      without the use of a contrast agent.

PMID- 8282890
TI  - Assessing myometrial invasion by endometrial carcinoma with dynamic MRI.
AB  - OBJECTIVE: Dynamic MRI was used to analyze patterns of contrast enhancement in
      muscle layers in the normal uterine body and to evaluate the depth of myometrial
      invasion by endometrial carcinoma. MATERIALS AND METHODS: Dynamic MRI was
      performed in 18 normal volunteers and 22 patients with endometrial carcinoma.
      Eight of the 18 normal volunteers were of reproductive age, and 10 were
      postmenopausal. The dynamic study was performed immediately after the bolus
      administration of gadopentetate dimeglumine. Twelve consecutive images, including
      the early phase images, were obtained during the first 2 min. The delayed phase
      image was obtained subsequently. RESULTS: An early enhancement zone of the inner
      muscle layer was demonstrated in 15 normal volunteers. In all patients in whom
      this early enhancement zone was preserved, the tumor was confined to < 50% of the
      muscle layer. In the evaluation of myometrial invasion, the accuracy of dynamic
      MRI was 91% compared with 77% on T2-weighted images. This improvement may be
      attributed to greater contrast and clearer demonstration of the border between
      tumor and myometrium in the early phase. CONCLUSION: We consider the disruption
      of the early enhancement zone of the inner muscle layer to be an important
      indicator of myometrial invasion.

PMID- 8282891
TI  - MRI of complicated anal fistulae: comparison with digital examination.
AB  - OBJECTIVES: The assessment of complicated anal fistulae is based on digital
      examination. Our objective was to study the potential role of MRI in this setting
      by comparing preoperative digital examination with MRI. MATERIALS AND METHODS:
      Digital examination and MRI were prospectively and blindly interpreted in 13
      patients with complicated anal fistulae. Surgical findings were used as standard.
      RESULTS: Complete agreement between the results of digital examination and the
      surgical findings was observed in 8 patients and between the results of MRI and
      the surgical findings in 12 patients. Digital examination misclassified two low
      transsphincteric fistulae as high transsphincteric and missed high secondary
      extensions or abscesses in three other patients. Magnetic resonance misclassified
      only one suprasphincteric fistula as low transsphincteric and did not overlook
      high secondary extensions or abscesses. CONCLUSION: These findings suggest that
      MRI may show abnormalities not detected by preoperative digital examination.

PMID- 8282892
TI  - Fibrous dysplasia associated with cortical bony destruction: CT and MR findings.
AB  - OBJECTIVE: Fibrous dysplasia is a benign disorder of bone that can cause cortical
      thinning as well as bony expansion. Full-thickness cortical bony destruction,
      however, typically characterizes more aggressive or malignant lesions of bone. We
      present three cases of fibrous dysplasia that illustrate this more aggressive and
      potentially confusing feature. MATERIALS AND METHODS: The findings on radiography
      and cross-sectional imaging studies are reviewed in three surgically proven cases
      of fibrous dysplasia that exhibited full-thickness cortical bony destruction.
      RESULTS: Well-defined cortical perforations without associated periosteal
      reaction were clearly seen on CT. This finding was suspected on plain radiography
      in only one of the three cases. A small associated soft tissue mass was detected
      by MR imaging in this case. Many cortical perforations were seen in the one case
      of polyostotic fibrous dysplasia. CONCLUSION: Full-thickness cortical bony
      destruction can be seen in fibrous dysplasia. This finding, which may only be
      evident on cross-sectional imaging studies, should not by itself alter a
      diagnostic impression of fibrous dysplasia supported by other radiographic and
      clinical features.

PMID- 8282893
TI  - Sacral pneumatocysts: CT appearance.
AB  - OBJECTIVE: CT findings of pneumatocyst of the sacrum have been evaluated.
      MATERIALS AND METHODS: Eight patients, six men and two women, with pneumatocysts
      of the sacrum were studied. Selective CT with 4 and 2 mm thickness was performed,
      and the intralesional attenuation coefficients were measured. RESULTS: All
      patients showed subchondral pneumatocysts of the sacrum with sclerotic margins
      related to the synovial portion of the sacroiliac joint. Intraarticular gas was
      found in six cases, and evidence of communication between the lesion and the
      joint was observed in two patients. Signs of bone degeneration were present in
      all cases. CONCLUSION: Pneumatocyst of the sacrum is a benign bone lesion
      associated with arthritic changes.

PMID- 8282894
TI  - High spatial resolution CT with a synchrotron radiation system.
AB  - OBJECTIVE: We describe a monochromatic X-ray CT system using synchrotron
      radiation, which has been constructed employing a vertical wiggler beam line at
      the National Laboratory for High-Energy Physics in Tsukuba, Japan. This CT system
      was produced to facilitate examination of the microstructures of material and
      biological specimens. MATERIALS AND METHODS: The system provides excellent
      contrast and has a spatial resolution capacity ranging from 2 to 100 mm. In this
      preliminary experiment, the images of the rat were obtained at 36-mm slice
      thickness and 33.2-keV X-ray energy. RESULTS: The nasal cartilage, skull, and
      teeth of a live rat were clearly demonstrated with 36-mm spatial resolution.
      CONCLUSION: Using a monochromatic X-ray CT system with synchrotron radiation,
      detailed structures of rat skull were imaged clearly.

PMID- 8282895
TI  - Stress and coping in adolescence. Introduction.

PMID- 8282896
TI  - Coping with challenge in adolescence: a conceptual model and psycho-educational
      intervention.
AB  - This paper presents a conceptual model for understanding the nature, timing,
      synchronicity and impact of developmental stressors and their implications for
      adolescent mental health trajectories. The model is derived, in part, from a
      longitudinal program of research investigating the development of adolescent
      mental health. Developments in the areas of life-span development, developmental
      psychopathology, and stress and coping also inform the model. In this model,
      stressors are viewed as challenges to the coping responses and resources of
      adolescents. Some challenges can be risks to adolescent mental health while
      others can be opportunities for further growth and development. Moderators of the
      association between challenge and mental health outcomes include
      internal/personal and external/interpersonal resources. This model has led to a
      psycho-educational program to enhance coping and reduce depression. Its design
      and some preliminary results from a longitudinal study of the short- and long
      term effectiveness of the program in enhancing adolescent mental health are
      described.

PMID- 8282897
TI  - Boys play sport and girls turn to others: age, gender and ethnicity as
      determinants of coping.
AB  - This paper reports a conceptualization of and our research to date in the area of
      adolescent coping. In particular, it reports on a study of Australian secondary
      students who completed an 80-item questionnaire which captures the range of
      adolescent coping behaviour by assessing eighteen strategies and three coping
      styles. When the relationship between coping behaviour and the respondents'
      gender, age and ethnicity was investigated, it was found that older students use
      more Self-blame and Tension-reduction techniques than do younger students; and
      younger students use more work related strategies than do older students; males
      report using more Physical Recreation than do females whilst females use more
      Seeking Social Support, Wishful Thinking and Tension-reduction strategies. In
      general, the pattern of usage of different coping strategies, for the students
      participating in this investigation, indicates that adolescents' foremost
      response to their general concerns comprises attempts to deal directly with the
      causes of concerns while attending to both their own physical and social well
      being.

PMID- 8282898
TI  - Close relationships and coping behavior in adolescence.
AB  - In line with the notion emphasizing the role of social support in individual
      coping, this paper discusses the role of close relationships during adolescence
      and their contribution to individual coping. Data from a series of studies
      conducted mainly on early adolescents show that the availability of family and
      peers combined with support of a youngster's independence contributes to
      individual adaptive coping. In addition, data show the contribution of close
      relationships to coping differs for males and females. It is suggested that
      though close relationships are crucial for coping with stress, their significance
      changes across context (family, peers) and gender during adolescence.

PMID- 8282899
TI  - Coping behavior in normal and clinical samples: more similarities than
      differences?
AB  - In our studies we tried to integrate a developmental and a clinical perspective
      on coping and adaptation in adolescence. Starting with a review of the author's
      own research, involving over 3000 12- to 20-year-olds from various cultures, the
      problems typical of this developmental phase and the ways of coping with these
      normative demands are presented. The results show that coping skills of young
      people in dealing with age-specific problems have so far been considerably
      underestimated. Their response to problems stemming from different developmental
      fields such as parents, peers, school or future involved three main modes of
      coping: Active Coping, Internal Coping and Withdrawal. Withdrawal was employed
      very rarely and only for certain types of problems. Age, gender and problem
      specific effects in coping were found. Whereas normal adolescents most frequently
      choose to cope with difficulties actively by means of social resources and to
      think out possible solutions, risk populations appear to have a more ambivalent
      pattern of coping strategies with high functionality and high dysfunctionality.
      Even their appraisal of problems is already disturbed; they feel more readily
      threatened by everyday problem situations and respond more uniformly with
      withdrawal. Finally, similarities between the female coping style in normal
      samples and the more pronounced ambivalent pattern in clinical samples were
      discussed and related to psychopathology.

PMID- 8282900
TI  - Family coping with an adolescent's chronic illness: an approach and three
      studies.

PMID- 8282901
TI  - Adolescent stress and coping: implications for psychopathology during
      adolescence.
AB  - Stressful experiences and efforts to cope with stress are central to
      understanding psychological distress and psychopathology during adolescence.
      Depressive phenomena during adolescence offer a particularly interesting
      opportunity for understanding the role of stress and coping processes in
      adolescent psychopathology. Research concerned with stress and coping during
      adolescence is reviewed, using depression as a key example of a consequence of
      stress and coping processes. Based on this research, it is hypothesized that
      exposure to and appraisals of interpersonal stress combine with aspects of
      biological development and the use of maladaptive coping strategies to account
      for the emergence of significant gender differences in depression and other forms
      of psychopathology during adolescence. Directions for future research in this
      area are highlighted.

PMID- 8282902
TI  - Tissue expansion. A new way to achieve an old goal in dermatologic surgery.

PMID- 8282903
TI  - A history of tissue expansion. Concepts, controversies, and complications.
AB  - BACKGROUND: Tissue expansion has become a widely used adjunct in reconstruction
      of the skin. OBJECTIVE: To trace the history of the concept of tissue expansion
      from the ancient to the latest medical literature. METHODS: We reviewed the
      technologic developments in the materials and methods of tissue expansion.
      RESULTS: Tissue expansion is of clinical importance and can be understood by the
      biochemical, biomechanical, and histologic features of expanded skin. CONCLUSION:
      Tissue expansion is becoming widely used and accepted and its continued use under
      many circumstances is justified by the experimental and clinical results.

PMID- 8282904
TI  - Histology and physiology of tissue expansion.
AB  - BACKGROUND: Tissue expansion is a concept based on the skin's natural ability to
      stretch in response to an underlying force. OBJECTIVE: The purpose of this
      article is to review the histological and physiological changes that occur within
      the soft tissue and underlying structures during tissue expansion. METHODS: An
      extensive search of the literature reviewing these changes is summarized herein.
      RESULTS: Conventional tissue expansion may result in epidermal hypertrophy,
      decreased dermal, muscle, and adipose thickness, and bone resorption. A vascular
      capsule and angiogenesis provides a highly vascular flap and improves flap
      viability. Few soft tissue changes occur during rapid tissue expansion. The
      ability of the skin to increase in surface area during conventional tissue
      expansion is primarily because of biological tissue creep. Rapid expansion may
      result from mechanical tissue creep. CONCLUSION: Many soft tissue changes occur
      during tissue expansion. Most of these changes return to the pre-expansion state
      over time following discontinuation of the expansion process.

PMID- 8282905
TI  - Intraoperative tissue expansion with the Foley catheter.
AB  - BACKGROUND: As surgeons face larger and more complex surgical defects, there is
      the continual search for more practical, successful, and cosmetically elegant
      methods for repair. Intraoperative tissue expansion is a relatively new technique
      built upon the fundamentals of traditional chronic tissue expansion. The Foley
      catheter is an inexpensive, readily available device that can be used for
      intraoperative tissue expansion. OBJECTIVE: The purpose of this article is to
      explain and demonstrate some of the uses for intraoperative tissue expansion with
      the Foley catheter. METHODS: A series of cycles of inflation and deflation of the
      Foley catheter balloon allows for gradual stretching of the skin over a period of
      15 to 20 minutes. RESULTS AND CONCLUSION: The "tissue gain" achieved via this
      technique often facilitates wound repair. The Foley catheter is a useful device
      and a significant addition to the dermatologic surgeon's armamentarium.

PMID- 8282906
TI  - Comparison of skin hooks and Foley catheters for immediate tissue expansion.
AB  - BACKGROUND: Immediate tissue expansion has been reported to expand skin
      sufficiently to permit primary closure of large facial defects up to 5 cm in
      diameter. OBJECTIVE: We wished to evaluate and compare skin hooks with foley
      catheters in producing tissue expansion. METHODS: Seven patients with post-Mohs
      surgery defects measuring 3.0 to 5.5 cm in diameter and located on scalp, temple,
      or forehead skin were treated with immediate tissue expansion. RESULTS: Immediate
      tissue expansion provided a 16 to 36% increase in the tissue available for
      closure, over and above what was achieved by undermining alone. In each case,
      adequate stretching of skin was achieved to permit primary closure relatively
      easily, which was not possible with undermining alone. Skin hooks were found to
      be equivalent to foley catheters in their ability to produce tissue expansion. At
      the one year follow-up visit, some spreading of the scar was noted, ranging from
      1 to 7 mm, which appears in part to be related to the degree to which the skin
      was expanded. CONCLUSION: These findings support the concept that immediate
      tissue expansion is a separate and distinct process from undermining, which
      provides additional tissue for reconstructive surgery.

PMID- 8282907
TI  - Chronic tissue expansion.
AB  - BACKGROUND: Chronic tissue expansion is an extremely useful addition to the
      dermatologic surgeon's skills. OBJECTIVE: To review chronic tissue expansion.
      METHODS: The relevant literature is summarized. Two case histories are presented
      as examples of the utility of chronic tissue expansion. RESULTS: The history of
      tissue expansion is briefly reviewed. Indications pertinent to the practice of
      dermatologic surgery are discussed. The devices themselves are described, as well
      as new experimental advances. The general procedure for utilizing tissue
      expanders is outlined, as well as relevant histologic changes that occur in
      expanded skin. Both common and rare complications are covered, with attention to
      prevention. CONCLUSION: Chronic tissue expansion provides an excellent means for
      obtaining extra tissue for cosmetic and reconstructive surgery.

PMID- 8282908
TI  - Permanent tissue expansion.

PMID- 8282909
TI  - Tissue expansion and Mohs micrographic surgery.
AB  - Tissue expansion is of value in the repair of some defects produced by Mohs
      micrographic surgery. In particular, defects of the nose, forehead, temple and
      scalp as well as extensive defects in other areas may require expansion. Tissue
      expansion should be considered prior to Mohs micrographic surgery in these cases.
      Intraoperative and rapid expansion are useful adjuncts to other repair options.
      Complications of expansion are frequent and must be anticipated.

PMID- 8282911
TI  - Intraoperative expander-assisted scalp reduction.

PMID- 8282910
TI  - Primary reconstruction of congenital facial lesion defects with tissue expansion.
AB  - BACKGROUND: Congenital facial lesions may require surgical intervention to
      correct deformity or to decrease the potential for malignant degeneration.
      OBJECTIVE: Hemangiomata and melanocytic and sebaceous nevi are among the most
      common congenital facial defects. The techniques and outcome of serial tissue
      expansion in the management of facial lesions were evaluated. METHODS: Seven
      pediatric patients had congenital facial defects treated with tissue expansion
      and subsequent excision and reconstruction. RESULTS: All patients had a
      satisfactory outcome. Complications are reviewed, and in this patient population
      were minor. CONCLUSIONS: Tissue expansion has a role in surgical management of
      congenital facial lesions. Staged excision, skin grafting and nonintervention are
      also options which must be individualized to the case at hand.

PMID- 8282912
TI  - Complications of tissue expansion.

PMID- 8282913
TI  - Curly lusterless hair: anatomic surface changes on transplanted hair shafts.

PMID- 8282914
TI  - Serial replacement of sutures for preventing suture marks.

PMID- 8282915
TI  - Peripheral tissue undermining is not the final answer to prevent trapdooring in
      transposition flaps.

PMID- 8282916
TI  - Dermatology and hospital liposuction privileges.

PMID- 8282917
TI  - Angiosarcoma treated by Mohs micrographic surgery.

PMID- 8282918
TI  - Flat affect in schizophrenia does not reflect diminished subjective experience of
      emotion.
AB  - Although accorded historical significance, affective features of schizophrenia
      have only begun to receive systematic empirical attention. Interestingly, both
      early psychopathology writers and more recent investigators have reported
      frequent discrepancies between schizophrenics' feelings and outward expressions
      of emotion. Using a more comprehensive assessment of emotion, the present study
      examines the relationship between emotional experience and expression in a sample
      of medication-free schizophrenics. Compared with their normal counterparts,
      schizophrenics were indeed much less facially expressive of both positive and
      negative emotions during emotion-eliciting films, yet they reported experiencing
      as much positive and negative emotion. Therefore, the blunted affect typical of
      some schizophrenics misrepresents their underlying emotional experience. Future
      research into an inhibition hypothesis is recommended.

PMID- 8282919
TI  - Relationships between symptoms of depression and anxiety and dysfunctional
      beliefs about achievement and attachment.
AB  - Psychiatric outpatients (N = 293) provided data to test the symptom specificity
      and final common pathway hypotheses about symptoms of depression and anxiety. The
      symptom specificity hypothesis predicts that the symptoms reported by a depressed
      or anxious patient depend on the dysfunctional beliefs he or she endorses. In
      contrast, the final common pathway hypothesis predicts that symptoms are
      unrelated to the types of beliefs the patient endorses. These hypotheses were
      tested in the context of theories that emphasize the importance of dysfunctional
      beliefs about achievement and attachment. Only limited support for the symptom
      specificity hypothesis was obtained; support was strongest for the link between
      attachment beliefs and anxiety symptoms. Relationships between symptoms and
      dysfunctional beliefs did not depend on psychiatric diagnosis.

PMID- 8282920
TI  - Differential effects of a misattribution manipulation on sexually functional and
      dysfunctional men.
AB  - Ten sexually functional and 10 dysfunctional men viewed sexually explicit films
      following ingestion of each of three placebo pills described as an erection
      enhancement pill, an erection detraction pill, and a placebo pill. Functionals
      evidenced a reverse placebo effect with significantly higher erectile response
      under the detraction relative to the enhancement and placebo conditions.
      Dysfunctionals evidenced a direct placebo effect with significantly lower
      erectile response under the detraction relative to the enhancement and placebo
      conditions. Fifteen Ss (75%) responded according to group patterns. Results
      suggest yet another arena in which functional and dysfunctional men respond in a
      fundamentally different manner. This pattern of differential responding may be
      due to relative differences in level of interoceptive awareness and/or
      interoceptive avoidance between functional and dysfunctional Ss and reflect on
      the nature of anxiety.

PMID- 8282921
TI  - Sustained attentional and disattentional abilities: differences between low and
      highly hypnotizable persons.
AB  - Relations between sustained attentional and disattentional abilities and hypnotic
      susceptibility (Harvard Group Scale of Hypnotic Susceptibility: Form A; Stanford
      Hypnotic Susceptibility Scale: Form C) were examined in 38 low (0-3) and 39
      highly (10-12) hypnotizable college students. Highs showed greater sustained
      attention on Necker cube and autokinetic movement tasks and self-reported greater
      absorption (Tellegen Absorption Scale) and extremely focused attentional
      (Differential Attentional Processes Inventory) styles. Hypnotizability was
      unrelated to dichotic selective attention (A. Karlin, 1979) and random number
      generation (C. Graham & F. J. Evans, 1977) tasks. Discriminant analysis correctly
      classified 74% of the lows and 69% of the highs. Results support H. J. Crawford
      and J. H. Gruzelier's (1992) neuropsychophysiological model of hypnosis that
      proposes that highly hypnotizable persons have a more efficient far frontolimbic
      sustained attentional and disattentional system.

PMID- 8282922
TI  - Depressive symptoms as a nonspecific, graded risk for psychiatric diagnoses.
AB  - Using data from a 16-year follow-up of a nationally representative sample of
      6,913 adults, measures of depressive symptoms were used to predict psychiatric
      diagnoses taken from hospitalization records. In proportional hazards analyses,
      two measures of depression were significantly associated with subsequent
      diagnoses of depression and other psychiatric disorders after statistical control
      for demographic variables and previous history of psychological problems.
      Depressive symptoms predicted late as well as early occurrence of psychiatric
      diagnoses and showed a pattern of increasing risk with increasing scores, even
      below clinical cutoffs. This pattern of results is consistent with the view that
      depressive symptoms predict future psychiatric disorders largely because they
      serve as proxy measures of some chronic vulnerability, such as the normal
      personality dimension of neuroticism.

PMID- 8282923
TI  - Fears of death in suicidal and nonsuicidal adolescents.
AB  - Suicidal, psychiatric, and normal adolescent girls and boys, ages 15-17 years,
      participated in a study on five types of death fears. A mixed within-between
      multivariate analysis of variance (5 factors x 3 groups) yielded significant
      interactive effects of indicating that there were different profiles of fears
      among the three groups: Relative to the other groups, suicidal adolescents
      displayed little differentiation between facets of fear, with differences in the
      magnitude of fear limited to the intrapersonal facets. Correlates of fear varied
      between groups: Fear was positively correlated with suicidality in normal
      subjects, negatively correlated with suicidality among suicidal ones, and
      unrelated to suicidality in the psychiatric group. It is suggested that fear of
      death is processed and experienced differently by suicidal and nonsuicidal
      adolescents to serve as a facilitator or inhibitor of suicidal behavior.

PMID- 8282924
TI  - Negative reciprocity and communication in couples with a violent husband.
AB  - To better understand the relationship dynamics of couples experiencing husband-to
      wife violence, the interaction patterns of 29 domestically violent (DV), 15
      distressed but nonviolent (DNV), and 13 happily married (HM) couples were
      examined using the Marital Interaction Coding System and lag sequential analyses.
      DV spouses were generally more often aversive and less often facilitative than
      nonviolent couples. DV couples were significantly more likely to engage in
      negative reciprocity than their DNV or their HM counterparts. DV wives were as
      likely as their husbands to reciprocate negative behavior. Furthermore, no
      support was found for a negative reinforcement hypothesis that husbands'
      aversiveness was shaped or maintained by wives' capitulation.

PMID- 8282925
TI  - Self-esteem and vulnerability to depression: the concurrent validity of interview
      and questionnaire measures.
AB  - In a cross-sectional study of 146 women, we examined the association of M.
      Rosenberg's (1965) self-esteem questionnaire and the Self-Evaluation and Social
      Support Instrument (SESS), an interview measure of self-esteem, with two major
      risk factors for depression--early adversity and negativity in current close
      relationships. Although both measures were related to the risk factors, only the
      SESS accounted for unique variance when the two measures were considered together
      and current depression was controlled. The results suggest that the reason the
      SESS has previously been more effective in predicting depression (G. W. Brown, B.
      Andrews, T. O. Harris, Z. Adler, & L. Bridge, 1986) is because it taps specific
      areas of self-dissatisfaction in real-life situations and is therefore less
      vulnerable to mood-state effects than the more global questionnaire measure.

PMID- 8282926
TI  - Callosal transfer in schizophrenia: too much or too little?
AB  - Evidence from diverse sources has pointed to an abnormality in callosal transfer
      in schizophrenia. To examine this further, a test was devised that measures
      Stroop interference and facilitation within and between the cerebral hemispheres.
      46 heterogeneous schizophrenic patients were tested, and it was found that
      lateralized Stroop effects were equivalent in the left and right hemispheres and
      did not differ from normal or psychiatric (affective disorder) control Ss. In
      control Ss, Stroop effects that required interhemispheric transfer of coded
      information were reduced relative to those requiring intrahemispheric transfer,
      whereas among schizophrenic Ss, greater Stroop effects were found in the
      interhemispheric condition, presumably reflecting increased callosal
      connectivity. An index of callosal transfer did not correlate with gender, age,
      or IQ in any of the groups, nor did it relate to clinical characteristics in the
      schizophrenic Ss. The results support a specific functional abnormality of
      excessive callosal transfer in schizophrenia, though its role in pathogenesis
      remains unspecified.

PMID- 8282927
TI  - Anhedonia and premorbid competence in young, nonpsychotic psychiatric inpatients.
AB  - Earlier studies have demonstrated a significant relation between scores on the
      Physical Anhedonia Scale--but not on the Perceptual Aberration Scale--and
      premorbid social adjustment in schizophrenics (Chapman, Chapman, & Raulin, 1976,
      1978; Schuck, Leventhal, Rothstein, & Irizarry, 1984). A similar relation between
      scores on these 2 scales and interpersonal competence in college students has
      also been noted (Beckfield, 1985; Haberman, Chapman, Numbers, & McFall, 1979;
      Numbers & Chapman, 1982). The present study extends this work by examining the
      relation of premorbid adjustment to scores on these 2 scales among young,
      nonpsychotic psychiatric inpatients. Consistent with the earlier findings,
      anhedonic Ss had poorer premorbid social competence when compared with
      nonanhedonic Ss, whereas no relation was found between scores on perceptual
      aberration and premorbid social competence.

PMID- 8282928
TI  - Cognition and life stress in depression: cognitive factors and the definition,
      rating, and generation of negative life events.
AB  - The relationship between cognitive factors and different conceptualizations and
      measures of life stress poses important questions for contemporary theories of
      depression. We examined whether cognitive factors (dysfunctional attitudes and
      attributional style) are related to the definition, rating, and generation of
      negative life events. Life events were assessed with both subjective self-report
      and more objective interview-based methods in endogenously depressed outpatients.
      The results partially support the hypothesis that cognitive factors are related
      to definition and severity ratings of self-report measures of particular types of
      life events. These relationships held primarily for achievement, as compared with
      interpersonal, events. The results also support the hypothesis that elevated
      scores on measures of cognition are associated with the number of objectively
      defined events occurring prior to the onset of depression, suggesting that some
      patients may generate the life events that in turn may initiate a depressive
      episode.

PMID- 8282929
TI  - Evaluating the hopelessness model of depression: diathesis-stress and symptom
      components.
AB  - The hopelessness model of depression posits that latent attributional diatheses
      combine with stressors to produce a specific subtype of depression characterized
      by a specific set of symptoms. Associations between attributional diathesis,
      stress, and symptoms were examined to test the prediction that hopelessness
      depressions are characterized by a specific symptom profile. Fifty-seven
      depressed outpatients were categorized into subgroups on the basis of whether or
      not they met the criteria of L. Y. Abramson, L. B. Alloy, and G. I. Metalsky's
      (1988) hopelessness depression, defined as a match in content domain between
      attributional diathesis and negative stressor. Support for hopelessness
      depression was mixed. The hopelessness subtype differed from other major
      depressions with respect to symptom profile. However, the differences in
      symptomatology were not wholly consistent with the predictions of the
      hopelessness model.

PMID- 8282930
TI  - An attributional analysis of expressed emotion in Mexican-American families with
      schizophrenia.
AB  - In this study we tested an attributional model of expressed emotion (EE) among
      Mexican-American families. A sample of 46 key family members of schizophrenic
      patients were measured on three dimensions: affect toward patient,
      controllability attributions, and level of EE. Consistent with an attributional
      model, we found that high EE families (defined on the basis of critical comments)
      viewed the illness and associated symptoms as residing within the patient's
      personal control, more so than did low EE families. We also found that
      attributions held by family members are related to their affective reactions.
      Specifically, family members who perceived the patient as having control over the
      symptoms of schizophrenia tended to express greater negative emotions such as
      anger and annoyance toward the patient than did family members who viewed the
      symptoms as beyond the patient's personal control. An examination of the types of
      affects found and their relationship to EE status is discussed, along with
      implications for this research.

PMID- 8282931
TI  - Negative cognitions and attributional style in depressed adolescents: an
      examination of stability and specificity.
AB  - Despite recent findings that the prevalence of unipolar depression is as high in
      adolescents as it is in adults, relatively little is known about the
      applicability of cognitive theories of depression to adolescents. The present
      study examined the nature, specificity, and stability of cognitive dysfunction in
      male and female depressed, remitted, and psychiatric control adolescents. Factor
      analysis of a diverse set of measures yielded two factors, labelled Negative
      Cognitions and Attributional Style. Scores on both these factors were related to
      a current diagnosis of depression. Results also indicated that there may not be
      complete recovery of cognitive functioning (or of depressed mood) with diagnostic
      remission of depression. Finally, whereas elevated scores on the Negative
      Cognitions factor appeared to be specific to depression, the depressed and
      psychiatric control adolescents did not differ with respect to their scores on
      the Attributional Style factor.

PMID- 8282932
TI  - Intellectual performance and school failure in children with attention deficit
      hyperactivity disorder and in their siblings.
AB  - We made psychiatric and intellectual assessments of 140 children with attention
      deficit hyperactivity disorder (ADHD), 120 normal controls, and their 303
      siblings. The index children were white, non-Hispanic boys. ADHD children were
      more likely to have had learning disabilities, repeated grades, been placed in
      special classes, and received academic tutoring. They also did worse on the
      Wechsler Intelligence Scale for Children--Revised (WISC-R). Among ADHD probands,
      comorbid conduct, major depressive, and anxiety disorders predicted school
      placement more than school failure or WISC-R scores. However, the
      neuropsychological disability of all ADHD children could not be attributed to
      comorbid disorders because those without comorbidity had more school failure and
      lower WISC-R scores than normal controls. Intellectual impairment was also
      increased among siblings of ADHD children. This provides converging evidence that
      the ADHD syndrome is familial.

PMID- 8282933
TI  - Close encounters: an examination of UFO experiences.
AB  - Ss who reported UFO experiences were divided into those whose experiences were
      nonintense (e.g., seeing lights and shapes in the sky) and those whose
      experiences were intense (e.g., seeing and communicating with aliens or missing
      time). On a battery of objective tests Ss in these 2 groups did not score as more
      psychopathological, less intelligent, or more fantasy prone and hypnotizable than
      a community comparison group or a student comparison group. However, Ss in the
      UFO groups believed more strongly in space alien visitation than did comparison
      Ss. The UFO experiences of Ss in the intense group were more frequently sleep
      related than the experiences of Ss in the nonintense group. Among the combined
      UFO Ss, intensity of UFO experiences correlated significantly with inventories
      that assessed proneness toward fantasy and unusual sensory experiences.
      Implications are discussed.

PMID- 8282934
TI  - Attention and schizophrenia: impaired modulation of the startle reflex.
AB  - The startle reflex (SR) elicited by abrupt stimuli can be modified by attention
      to nonstartling stimuli that shortly precede the startle-eliciting stimulus. The
      present study of 15 recent-onset, relatively asymptomatic schizophrenic
      outpatients and 14 demographically matched normal control subjects demonstrated
      that attentional modulation of SR is impaired in schizophrenic patients.
      Specifically, the control group exhibited greater startle eye-blink modification
      following to-be-attended prestimuli than following to-be-ignored prestimuli,
      whereas the patients failed to show the attentional modulation effect. These
      results suggest traitlike attentional deficits in schizophrenia because the
      patients were relatively asymptomatic. The measurement of attentional modulation
      of SR may provide a nonverbal, reflexive, state-independent marker of the
      vulnerability to schizophrenia.

PMID- 8282935
TI  - Effects of changing contingencies on the behavior of depressed and nondepressed
      individuals.
AB  - The effects of rules versus shaping on the behavior of depressed and nondepressed
      individuals were compared. Extending the findings in the depressive realism
      literature to a learning paradigm, the behavior of depressed individuals was more
      sensitive to changing contingencies than was the behavior of nondepressed
      individuals. Contrary to hypotheses, however, this effect appeared due primarily
      to the nondepressive Ss' strategy of continuing to follow an experimenter's
      inaccurate rules. Results suggest the relative absence of self-presentational
      concerns may lead depressed individuals to be more accurate in judging
      environmental contingencies.

PMID- 8282936
TI  - Impasses in psychoanalysis: overcoming resistance in situations of stalemate.
AB  - Many impasses occur in treatment when the patient fears that analysis will repeat
      frightening or disappointing experiences. These stalemates result from the
      patient's conviction that the analyst has confirmed a preexisting belief that is
      central to the patient's primary conflict. Frequently, this belief involves an
      unacceptable or frightening self- or object representation. At these times,
      intense resistance and strong negative transference/countertransference reactions
      may develop. Impasses are differentiated from these strong negative reactions
      only by virtue of the fact that they remain unanalyzed. The factors that create
      these negative states can best be understood in instances where the potential
      impasse is resolved. When impasses persist, most often patients leave treatment.
      Under these circumstances, we can try retrospectively to understand what has gone
      wrong, but without the patient's confirmation, our conclusions must remain
      speculative. Four cases illustrate varying degrees of analysis and resolution of
      resistance and transference/countertransference binds.

PMID- 8282937
TI  - In search of psychoanalytic technique: perspectives from on the couch and from
      behind the couch.
AB  - The author's experience as a patient in analysis with four different analysts is
      recounted. Similarities and differences in technique, especially with regard to
      overall analytic atmosphere, use of interpretation, reconstruction of childhood,
      dream interpretation, self-revelations of the analyst, and the way politics was
      discussed are compared. The author concludes that major differences in
      personality and temperament of the four analysts made a substantial difference in
      the experience of analysis. Finally, the author discusses whether such
      differences are indeed important, and in what sense we can speak of the place of
      analytic technique. Is it a body of teaching and practice that is aimed at
      minimizing the differences attributable to individual analysts' style and
      temperament, or is it a body of teaching and practice, still to be elaborated,
      that gives us a full and flexible account of how analysts actually function?

PMID- 8282938
TI  - Psychoanalytic technique and the development of the capacity to reflect.
AB  - The capacity to reflect is an essential precondition for the existence and
      maintenance of an analytic process. This paper describes the technical
      environment that may enable the functional emergence and management of this
      precondition. In order that the specific features of such an environment may be
      addressed, psychoanalysis is differentiated from psychotherapy in terms of goals,
      and this is followed by a discussion of technical modalities that reflect
      uniquely analytic aims. In conjunction with these technical considerations, the
      underpinnings of the psychoanalytic situation are described as an "envelope of
      experience" within which the patient may develop the reflective capacity to
      participate in the analytic process. Finally, the acquisition of this essential
      reflective capacity is viewed in the context of a developmental line in an
      analysis, and is highlighted through the use of a clinical example.

PMID- 8282939
TI  - Developmental transformations: the Isakower phenomenon as an example.
AB  - A review of the literature, and clinical analytic material suggest that the
      Isakower phenomenon and its variants consist of representations or sense memory
      traces of the original infantile feeding experiences integrated with later
      representations of experiences during the anal and oedipal stages, latency, and
      even later. With progressive development, memories of earlier experiences are
      transformed with regard to function, form, content, and meaning.

PMID- 8282940
TI  - The deficit syndrome in schizophrenia: psychoanalytic and neurobiological
      perspectives.
AB  - The author summarizes recent advances in neurobiological research which appear to
      offer compelling evidence that the most pathognomonic feature of schizophrenia,
      the deficit or negative syndrome, is associated with functional abnormalities in
      the frontal lobe of the brain. These brain abnormalities are correlated with
      those conceptualized by psychoanalytic theories of withdrawal of libido and loss
      of mental representation. In the light of this data, the author expresses serious
      reservations about three psychoanalytic formulations concerning the causes of the
      deficit syndrome: (1) the syndrome represents, in a primary rather than a
      secondary way, a psychological defense; (2) it is caused by severe conflicts or
      neglect during early childhood which lead to impairments in the building up of
      psychic structure and mental representation; (3) difficulties with the aggressive
      drive play a primary etiological role.

PMID- 8282941
TI  - Psychoanalysis, psychobiology, and homosexuality.
AB  - The potential role of biological influences in human sexual orientation was
      considered more seriously during the early phases of psychoanalysis than in the
      years since World War II. Recently studies of homosexuality and heterosexuality
      in the neurosciences have attracted widespread attention both in the scientific
      and lay communities. The salience of these new data for psychoanalytic theory and
      practice is just beginning to be explored. In this article, we review research on
      sexual orientation in the following areas: genetics, crosscultural studies,
      studies of development in individuals with abnormal prenatal hormone exposure,
      childhood play patterns, and brain studies in both nonhumans and humans.
      Differences between male and female homosexuality are explored. We propose that
      psychoanalytic theory can grow and profit from a careful consideration of new
      findings in the psychobiology of sexuality, and that the interaction between mind
      and body is the appropriate purview of psychoanalysis.

PMID- 8282942
TI  - Reflections on the history of psychoanalysis.
AB  - The proliferation of psychoanalytic schools demands the reexamination of the
      history of psychoanalysis. Psychoanalysis emerged at the intersection between the
      rational heritage of the enlightenment and the interest in the morbid that was
      the hallmark of romanticism. This paper focuses on moments when psychoanalysis
      was poised at a crossroads where various routes could have been taken.
      Differentiation is made among the heretics, modifiers, and extenders of
      psychoanalysis. Discussed within a historical frame of reference are the
      contributions of leading modifiers--Melanie Klein, Hartmann, Winnicott, Kohut,
      and others--as well as their extenders. The paper concludes with a discussion of
      some current urgent problems facing psychoanalysis.

PMID- 8282943
TI  - Measuring the ghost in the nursery: an empirical study of the relation between
      parents' mental representations of childhood experiences and their infants'
      security of attachment.
AB  - This paper presents a summary of the Anna Freud Centre-University College London,
      Parent-Child Project. Its most important finding was that the security of the
      infants' relationship with both parents at 12 and 18 months could be predicted on
      the basis of qualitative aspects of the parents' accounts of their own childhoods
      collected before the birth of the child. This confirmed Selma Fraiberg's
      observations concerning the reemergence of childhood conflicts at early stages of
      childbearing. Possible mechanisms mediating this link are explored with
      particular reference to the role of the parents' accurate mental representations
      of the infants' mental world.

PMID- 8282944
TI  - On psychoanalytic listening: language and unconscious communication.
AB  - The authors review past and recent perspectives on psychoanalytic listening, then
      present a synthetic model founded on psycholinguistics and semiotics. They argue
      that the analytic listening process can be broken down into nonlinguistic
      communications and--most important--linguistic categories pertaining to
      narrativity, symbolic reference, form, and interactive conventions. In each of
      these areas of signification, the authors present the ways in which the technique
      of psychoanalytic listening attends to unconscious meanings, thereby differing
      from ordinary listening which "hears," at best, only denotative and connotative
      meanings.

PMID- 8282945
TI  - Micturitional disturbance in progressive supranuclear palsy.
AB  - Detailed micturitional histories were taken from nine patients with progressive
      supranuclear palsy (PSP), and eight of them (89%) had micturitional symptoms
      including urinary incontinence in seven. Urodynamic studies were performed in six
      patients and the results were as follows. Three had residual urine of 100 ml on
      average. Four had detrusor hyperreflexia and one had a low compliance
      cystometrogram. One had detrusor-sphincter dyssynergia. Motor unit analysis of
      external sphincter was performed in four patients and two had neurogenic changes.
      The results were compared with our previous findings in Parkinson's disease and
      in striato-nigral degeneration (SND), and we found that a severe degree of
      micturitional disturbance in PSP seems to be as common as in SND, especially in
      the urinary storage phase, and more frequent than in Parkinson's disease.
      Supranuclear types of pelvic and pudendal nerve dysfunctions seemed to be mainly
      responsible for micturitional disturbance in PSP.

PMID- 8282946
TI  - The amplitude of synchronized cardiac sympathetic nerve activity reflects the
      number of activated pre- and postganglionic fibers in anesthetized cats.
AB  - In order to obtain information regarding the number of pre- and postganglionic
      fibers that are firing, we measured cardiac sympathetic nerve activity (CSNA)
      before and after the successive sectioning of T1-T5 thoracic rami in anesthetized
      cats. Total activity from the area was measured under the mean CSNA curve. Peak
      amplitude, width and periodicity of the synchronized discharge was analyzed from
      the CSNA curve by the method we developed. Total CSNA decreased to 91 +/- 6%, 63
      +/- 6%, 27 +/- 10%, 8 +/- 6% and < 1% of the control due to successive section of
      the T5, T4, T3, T2 and T1 rami, respectively. The peak amplitude of synchronized
      CSNA decreased to 95 +/- 6%, 73 +/- 8%, 40 +/- 5% and < 10% of the control value,
      due to section of the T5, T4, T3 and T2 rami, respectively. The control width was
      107 +/- 8 ms and decreased to 106 +/- 1 ms, 92 +/- 6 ms and 68 +/- 5 ms by
      successive section of the respective T5, T4 and T3 rami. However, periodicities
      of 80-120 ms (Tc rhythm) and 140-500 ms (Tb rhythm) of synchronized CSNA remained
      unchanged after section of the T3-T5 rami. The total CSNA decreased gradually due
      to decreases in the peak amplitude and width of synchronized CSNA with the
      successive section of preganglionic fibers. These results indicate that the peak
      amplitude of synchronized CSNA reflects the number of pre- and post-ganglionic
      fibers that are firing and suggest that the number of preganglionic neurons which
      activate the cardiac fibers naturally was largest in the T3 segment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8282947
TI  - Proliferation of mast cells in the smooth muscle of denervated rat jejunum.
AB  - Mast cell hyperplasia and changes in phenotypic characteristics subsequent to
      myenteric and extrinsic denervation of a segment of rat jejunum were studied. The
      myenteric plexus and extrinsic nerves were ablated by serosal application of the
      cationic surfactant benzyldimethyltetradecylammonium chloride. There was a four
      fold increase in the number of mast cells in the smooth muscle layers 15 days
      after denervation. This increase was sustained for at least 90 days after
      treatment. No increase in mast cell number was observed in the villus-crypt axis
      of the jejunum. Berberine sulfate fluorescent detection of heparin-containing
      mast cells demonstrated that a change in mast cell phenotype occurred between 20
      and 90 days after the denervation procedure. The fact that myeloperoxidase
      activity was the same in denervated and control tissue within 5 days of
      denervation demonstrates the lack of a chronic inflammatory reaction. Our results
      suggest that mast cells might play a role in the gut wall re-modeling processes.

PMID- 8282948
TI  - Sympathetic innervation of the surface of the mouse vas deferens.
AB  - The distribution of axons and axon varicosities on the surface of the mouse vas
      deferens has been determined following fluorescence of these structures with 3,3
      diethyloxardicarbocyanide (DiOC2 (5)) to locate varicosities and FAGLU to detect
      catecholamine containing nerves. Small bundles of fluorescent axons treated with
      DiOC2(5), were shown to give rise to single or very small bundles of 2 or 3
      varicose axons that passed over the surface of the muscle bundles. Varicosities
      had the same average diameter of 0.9 microns, length of 1.1 micron and spacing
      apart of 4.6 microns whether identified following DiOC2(5) fluorescence or the
      FAGLU method for catecholamines and this was shown statistically to imply that
      they came from the same population of varicosities. Serial thin sections through
      small axon bundles and single axons, viewed with the electron microscope,
      confirmed the dimensions of varicosities along axons observed following DiOC2(5)
      staining or use of the FAGLU method.

PMID- 8282949
TI  - [Results of 30 keratoprostheses with retrocorneal fixation].
AB  - Keratoprosthesis is the last solution for corneally blind patients who cannot
      benefit from corneal grafts. The indications are limited to blind patients with
      monophthalmia and bilateral problems that are otherwise untreatable. After
      implanting the Choyce and Strampelli's devices for more than 10 years, we
      abandoned these anterior fixation techniques and now use a keratoprosthesis in
      which the sole mechanical fixation consists of a posterior support which is
      subsequently sealed by the fibrosis produced by the endothelial-Descement
      tissues. This new prosthesis is made of two pieces, an optic and an haptic
      fashioned out of CQ-PMMA. To minimize expulsion, the haptic outer diameter is
      greater than the central corneal orifice through which the optic is inserted and
      screwed into the haptic. The keratoprosthesis refractive power can be easily
      adjusted after lensectomy by changing the 40 D for a 63 D optic. The prosthesis
      is implanted in a single step surgical procedure, and can be implanted in phakic
      eyes while respecting the physiology and anatomy of these fragile eyes. This
      single step procedure reduces the usual repeated operations required when using,
      other techniques. We operated 12 cases of pseudopemphigus, 9 cases of burns, 7
      cases of trachoma, and 2 cases of pseudophakic oedema with good cosmetic and
      visual results with a follow-up ranging from several months to more than 3 years.
      The results obtained with this new keratoprosthesis are encouraging. The results
      have been analysed and classified into: anatomic and functional success 20 cases,
      anatomic success and functional failures 4 cases, anatomic failures 6 cases.

PMID- 8282950
TI  - [Insertion of the Tenon capsule onto the rectus muscles].
AB  - The localisation and definition of the capsule of Tenon insertion on the rectus
      muscles is of prime importance to the strabismus surgeon. The depth of the
      superior sub-Tenon space was measured on 22 adult human eyes after fixation in
      formalin. Although the measurements revealed major differences between the eyes,
      the following results were found: inferior rectus muscle = 7.8 mm +/- 1.79 (5.2
      13.0), medial rectus = 12.6 mm +/- 2.15 (8.4-17.2), superior rectus muscle = 16.7
      mm +/- 2.39 (12.7-21.5), and lateral rectus muscle = 19.0 mm +/- 2.19 (14.5
      22.0). Histological studies of 2 other human eyes confirmed the notion of a band
      of insertion on rectus muscles as the posterior limit of the sub-Tenon space. As
      far as this insertion, the capsule of Tenon is a dense connective tissue composed
      of many collagen and elastin fibers, but after the band insertion, it becomes
      virtual through its fusion with the perimysium of the rectus muscle.

PMID- 8282951
TI  - [Statistical study of the results of radial keratotomy].
AB  - The statistical study of 384 R.K. performed by the same surgeon shows that in 82%
      of R.K., preoperative myopia was between -1.5 to -6 diopters and in 77.5% of
      R.K., postoperative refraction was between -1 to +1. The 90% confidence interval
      was between -2 to +1 for all preoperative myopias and was the best when
      preoperative myopia was between -0.5 to -3 diopters (-1 to +1 D). The study of
      the stability and security shows that this surgical technique is stable and gives
      a good security.

PMID- 8282952
TI  - [Value of corticoids in the treatment of postoperative endophthalmitis].
AB  - Postoperative endophthalmitis, which has a dreadful reputation, needs early and
      aggressive treatment. Apart local and systemic antibiotic therapy, the place of
      corticosteroid treatment is still discussed. The authors retrospectively compared
      three groups of patients treated with appropriate antibiotics but with different
      corticosteroid. Group I received high dose corticosteroids early regimen, group
      II received delayed corticosteroids treatment and group III did not receive
      corticosteroids. Visual recovery as well as vitreous transparency better in group
      I.

PMID- 8282953
TI  - [Ocular lesions caused by pellet guns. Epidemiological study on 160 patients].
AB  - We present a retrospective study of ocular trauma related to pellet guns. Over a
      period of 5 years, 160 such patients were seen in our emergency unit. Eighty per
      cent of cases were men, with a mean age of 28 years. Ocular trauma was due to a
      fight in 85%. Ocular trauma was unilateral in 109 patients, and bilateral in 51
      patients. We observed a complete disorganisation of the eye in 8 eyes,
      intraocular foreign bodies in 71 eyes, intraorbital foreign bodies without ocular
      lacerations in 23 eyes, and blunt trauma in 108 eyes. Final vision was poor or
      absent in 31 eyes.

PMID- 8282954
TI  - [Cataract surgery in patients with myopia].
AB  - Cataract surgery in myopic eyes can be difficult. We present a retrospective
      study of 97 myopic eyes, with axial length of at least 26 mm. All eyes,
      extracapsular extraction with or without intraocular posterior chamber lens. Mean
      follow up is 14 months, and 54% of cases have a 1 year follow up. In only one
      case did a retinal break without retinal detachment appear after surgery, that
      was successfully treated with argon laser photocoagulation. A longer follow up of
      our cases will be necessary to estimate long term complications of cataract
      extraction in myopic eyes.

PMID- 8282955
TI  - [Probability studies on the variations of anterior corneal astigmatism].
AB  - The probability method of analysis of astigmatism variations respects both
      astigmatism components, quantity and axis. The two random variable model that we
      introduce here analyses cylinder variations and axial variations. After
      describing the contingency table and the probability table. Expectation of each
      component and its confidence interval are calculated together with the variance
      and the standard deviation. Covariance and correlation are calculated. If we want
      to compare different groups we test cylinders with cylinders and axes with axes.
      This method does not distort reality and is applicable to the semi meridians from
      0 degree to 360 degrees. Only large samples of patients can be studied by this
      method.

PMID- 8282956
TI  - [Vectorial models for analyzing variations of anterior corneal astigmatism].
AB  - Several studies have analysed postoperative or spontaneous variations in
      astigmatism. The methods of quantification of these variations, frequently used
      in these studies, are based on different ways of calculating: subtraction,
      vectorial or polar methods: Naylor, Jaffe and Clayman, Cravy, Naeser, Russell et
      al. and recently, Holladay et al. Although these methods have the advantage of
      taking into account the axial component of astigmatism and are useful for a
      single patient, they have many problems and they are more and more numerous (five
      in the last three years). We have computerized these formulae on a personal
      computer and studied their performances when the cylinder power decreases without
      modification of the axes, when the axes are modified without modification of the
      cylinder power and when the two axes change with the same angular difference.
      These calculations demonstrate that these formulae are not linear and introduce
      statistical errors before the statistical decision tests. Moreover, their
      application is only possible for evaluation of astigmatism axes between 0 degree
      to 180 degrees and not for semi meridians and corneal topography.

PMID- 8282958
TI  - [Treatment of retinal degeneration].

PMID- 8282957
TI  - [A case of Tolosa Hunt syndrome].
AB  - The authors review the clinical signs, results of investigations and clinical
      course under treatment of the Tolosa-Hunt syndrome; they illustrate their case
      presentation with a complete sequence of the imaging and the clinical and
      radiological findings of a case which fits the classical description found in the
      literature. They insist on the term of syndrome rather than disease because of
      the obvious diversity of anomalies encountered in this condition.

PMID- 8282959
TI  - [A valve for microsurgical decompression of optic nerve sheets].
AB  - The authors describe a valve for optic nerve sheath fenestration. The valve is
      composed of a silicone tube with one end placed between the two layers of the
      arachnoid at the top of the optic nerve head and the other end blocked but
      laterally fenestrated with two slits, fixed to the sclera with two small silicone
      wings. The pressure inside the tube can open the two slit openings when greater
      than ten millimetres of mercury. This valve has been designed in order to obtain
      a better function for optic nerve sheath fenestration operations.

PMID- 8282960
TI  - [Fungal keratitis with annular infiltration and hypopyon].
AB  - Fungal keratitis is a rare disease in Northern Europe. We report the case of a 57
      year-old female suffering from a paracentral corneal ulcer, following minor
      corneal trauma with a branch of a tree. Clinically, the ulcer was associated with
      a ring infiltrate and a hypopyon. Corneal smears and cultures were negative. As
      the corneal lesions and the hypopyon progressed despite maximal treatment,
      penetrating keratoplasty was performed on the assumption of a fungal origin.
      Histopathologic examination revealed pseudohyphae, morphologically compatible
      with a candida species. The clinical picture, its differential diagnosis and the
      diagnostic methods are discussed.

PMID- 8282961
TI  - Treatment with a gonadotropin-releasing hormone agonist in acne or idiopathic
      hirsutism.
AB  - Six women with acne and six women with hirsutism were treated with the GnRH
      analog [D-Ser(Bu(t))6] LHRH-(1-9)ethylamide (Buserelin) for 6 months (nasal
      spray, 1,200 micrograms/day) to suppress ovarian steroidogenesis. All women were
      eumenorrheic and did not demonstrate any adrenal or ovarian dysfunction. During
      treatment, ovarian steroids, LH and FSH decreased, while DHEA-S showed minor
      modifications; the clinical score for both acne and hirsutism showed a
      significant reduction. Moreover, acne and hirsutism were still well controlled 6
      months after therapy. Gonadal function resumed in all patients after
      discontinuation of therapy. Three patients suffered from hot flashes from the 4th
      month. These data demonstrate that suppression of ovarian steroid secretion might
      be an efficient treatment in women suffering from acne or idiopathic hirsutism,
      indicating that ovarian steroids may have a key-role in the pathogenesis of these
      conditions.

PMID- 8282962
TI  - Lack of influence of aromatase and 5 alpha-reductase inhibition on [3H]imipramine
      binding in the male rat brain.
AB  - In intact adult male rats an inhibitor of aromatase and an inhibitor of 5 alpha
      reductase did not change the characteristics of [3H]imipramine binding sites in
      cerebral cortex, hypothalamus, and hippocampus. Testosterone, estradiol and
      dihydrotestosterone prevented the effect of castration on the number of
      [3H]imipramine binding sites, but had no effect in non-castrated animals. These
      data suggest that testosterone and its major metabolites, estradiol and
      dihydrotestosterone, are equally effective with regard to imipramine binding
      sites.

PMID- 8282963
TI  - Computer assisted sperm motility analysis at the moment of induced pregnancy
      during gonadotropin treatment for hypogonadotropic hypogonadism.
AB  - Two azoospermic patients with isolated hypogonadotropic hypogonadism (IHH) no.
      1,24-year-old, and no. 2,31-year-old), never treated before, were given
      gonadotropin therapy (GT), (FSH, 225 IU/week, and HCG, 4000 IU/week) and followed
      up monthly for sperm characteristics. After 6 (no. 1) and 9 (no. 2) months of
      treatment, immotile spermatozoa appeared in the semen. Two months later motile
      spermatozoa also appeared. A motile sperm concentration sufficiently high for
      computer motion analysis (CASA) was achieved 1 month later 9th and 12th month,
      respectively. At the 13th (no. 1) and 17th (no. 2) month of GT, CASA showed a
      small population of spermatozoa with a very good motility pattern. In the next
      ovulatory cycle the patients' partners became pregnant.

PMID- 8282964
TI  - The long-term effect of a calcium diet on the bone tissue, C-cells and
      parathyroid glands of the rat.
AB  - In this experiment of 11 month-duration, 18 female Wistar rats received
      controlled amounts of calcium with food and water, to produce a state of either
      hypocalcemia or hypercalcemia. After a long-term low calcium diet hypocalcemia
      disappeared. This group of animals showed insignificant increases in the nuclear
      cytoplasmic ratio of the parathyroid cells as well as in the total volume of the
      parathyroid glands, and a significant increase in the volume density of the
      osteoid. In the group receiving a high calcium diet, hypercalcemia was still
      present after 11 month. The insignificantly smaller and more numerous C-cells
      produced more calcitonin than normally. The parathyroid cells were significantly
      smaller and the numerical areal density of the osteoclasts was significantly
      lower than in the control group. It can be concluded that the parathyroid glands
      and C-cells are involved in the maintenance of blood calcium homeostasis during a
      long-term experiment on rats receiving low or high calcium diet.

PMID- 8282965
TI  - Insulin-like growth factor I values in patients on maintenance hemodialysis:
      relationship to growth hormone and albumin levels.
AB  - Twenty-seven uremic patients (blood urea: 58.2 +/- 2.2 mmol/l; blood creatinine:
      1,069 +/- 53 mumol/l; mean +/- SE) on maintenance dialysis were investigated
      immediately before and after a dialysis session. Control data were obtained from
      30 normal volunteers. Before dialysis, circulating levels of insulin-like growth
      factor I (IGF-I) were similar in anuric and nonanuric patients, averaging 305 +/-
      24 micrograms/l, a value not different from that observed in normal controls (262
      +/- 16 micrograms/l). IGF-I levels were not modified by dialysis. In contrast, GH
      values were significantly higher in uremic patients (3.6 +/- 0.6 microgram/l)
      than in normal controls (2.5 +/- 0.5 microgram/l) and decreased significantly
      after the dialysis session (0.8 +/- 0.1 microgram/l). IGF-I values were
      positively correlated with GH and albumin, but not with the various parameters of
      renal insufficiency, suggesting that in chronic renal failure, synthesis of IGF-I
      appears to be regulated, as in normal subjects, by growth hormone and nutritional
      status.

PMID- 8282966
TI  - Development of autoimmune thyroid dysfunction after bilateral adrenalectomy in a
      patient with Carney's complex and after removal of ACTH-producing pituitary
      adenoma in a patient with Cushing's disease.
AB  - Although the factors that cause developments or exacerbations of autoimmune
      thyroid dysfunction are not known, the changes of glucocorticoids might modulate
      the autoimmune responses. We compared the postoperative changes in thyroid
      function in one patient with Carney's complex with primary adrenocortical nodular
      dysplasia (PAND) and 19 patients with Cushing's disease due to ACTH-producing
      pituitary adenoma. Thyroid dysfunction developed after surgery for glucocorticoid
      excess in two patients; one with Carney's complex had transient hypothyroidism
      after bilateral adrenalectomy for PAND, and the other had transient
      hyperthyroidism due to thyroiditis after removal of ACTH-producing pituitary
      adenoma for Cushing's disease. Both patients had no thyroid autoantibodies at the
      time of surgery. None of the remaining 18 patients had clinically evident thyroid
      disease or increased antithyroidantibody titers. Development of autoimmune
      thyroid dysfunction may be observed after surgery for glucocorticoid excess in
      the patients with any forms of Cushing's syndrome, even who do not have thyroid
      antibodies.

PMID- 8282967
TI  - Coexistence of growth hormone-secreting pituitary adenoma and intracranial
      meningioma: a case report and review of the literature.
AB  - The simultaneous occurrence of a pituitary adenoma and an intracranial meningioma
      is a rare event. We report the coexistence of an eosinophilic pituitary adenoma
      and a endotheliomatous meningioma, in the sellar region, and evaluate their
      endocrine, neuro-radiological and immunohistochemical pattern. A 47-year-old
      woman affected by acromegaly was referred to us. Serum GH level was 82 ng/ml and
      remained unresponsive to both OGTT (75 g per os) and iv. GHRH 1-29 (100
      micrograms); IGF-1 was 807 ng/ml. Eight hours after acute sc administration of
      octreotide (100 micrograms) GH returned to normal levels (2.3 ng/ml). CT scan
      showed a large intra- and suprasellar mass involving the right cavernous sinus,
      with a retrosellar extension along the tentorium. A slight and inhomogeneous
      enhancement, with a periferal rim of bright signal was apparent at MRI.
      Conversely, the retrosellar component showed a bright homogeneous enhancement.
      The patient, therefore, underwent neurosurgery. Histological examination revealed
      the coexistence of 2 types of tissue: areas of endotheliomatous meningioma were
      interspersed among sheets of acidophilic adenoma tissue. Immunohistochemical
      analysis was performed in order to determine the relationship between the two
      masses: a positive staining for GH was shown in the areas of adenoma, as against
      for GHRH, neither in the adenomatous tissue nor in the slices of meningioma.
      Although MRI showed a latero-sellar post-surgical residual of meningioma, serum
      GH value was < 1 ng/ml. In conclusion, the relationship between the GH-secreting
      adenoma and the meningioma is unclear; however the GH-hypersecretion is not
      induced by a hypothetic GHRH-activity from the meningioma.

PMID- 8282968
TI  - Pseudopseudohypoparathyroidism associated with idiopathic growth hormone
      deficiency. Role of treatment with biosynthetic growth hormone.
AB  - A case is presented of a prepubertal girl with the characteristic somatic
      features of Albright's hereditary osteodystrophy, including severe short stature,
      cataracts and shortening of all metacarpals and metatarsals and of the second
      middle hand phalanges, whose diagnosis of pseudopseudohypoparathyroidism (PPHP)
      was confirmed by laboratory evaluation (normocalcemia, normophosphatemia, normal
      levels of circulating PTH and normal response to exogenous PTH). Since an
      isolated idiopathic GH deficiency has been diagnosed at the age of 9.7 yr, by an
      abnormal GH response to standard provocation tests, a poor spontaneous nocturnal
      GH secretion and a blunted response to GHRH test, our patient was treated with
      biosynthetic GH during a 3.5-year period. Although a good improvement of growth
      velocity was obtained when comparing pretreatment height velocity (4 cm/yr) with
      growth velocity evaluated during GH treatment (6.6, 6.2 and 5.9 cm/yr in the
      first, the second and the third year of therapy, respectively), bone age advanced
      more rapidly than chronological age, so that it is uncertain whether the growth
      acceleration promoted by GH administration really improved final height, which
      remained below the third centile. Our patient is the first described case of PPHP
      associated with idiopathic GH deficiency, and the second report of long-term GH
      treatment in a subject with PPHP. Further observations are necessary to define
      the frequency and significance of GH deficiency and the role of GH replacement
      therapy in pseudohypoparathyroidism- and PPHP-associated short stature.

PMID- 8282970
TI  - Selecting animal models of human aging: inbred strains often exhibit less
      biological uniformity than F1 hybrids.
AB  - Most gerontological research is conducted using inbred strains of animals in an
      attempt to maximize phenotypic uniformity within experiments and thus increase
      the experimenter's statistical power to detect treatment effects. However, for a
      wide range of phenotypic traits, F1 hybrids between inbred strains are
      considerably less variable than the parental inbred strains themselves.
      Therefore, the use of F1 hybrids is preferable for many research applications. In
      this article, we discuss the sources of phenotypic variability and explain why F1
      hybrids are often less variable than inbred strains; we review the empirical
      literature illustrating the large range of species and traits for which this is
      true; and finally we suggest how this finding suggests that F1 hybrids may often
      be superior animal models for studying the aging process and how to manipulate
      it.

PMID- 8282971
TI  - Influence of aging on the alpha 1-receptor-mediated glycogenolysis in rat
      hepatocytes.
AB  - The involvement of the Ca(2+)-dependent and Ca(2+)-independent, insulin-sensitive
      pathway in the alpha 1-receptor-control of glycogenolysis was investigated in
      hepatocytes from young adult, mature adult, and senescent rats. Upon chelation of
      extracellular Ca2+, phenylephrine caused a similar increase in glucose output
      that was potently inhibited by insulin, indicating the presence of both pathways
      in each age group. From the age-related decreasing sensitivity of the Ca(2+)
      dependent pathway toward verapamil and nifedipine, and toward insulin, we suggest
      that the contribution of Ca(2+)-fluxes in eliciting glycogenolysis through the
      Ca(2+)-dependent pathway decreases upon aging. Both pathways were inhibited by
      the protein kinase C (PKC) activator, 4 beta-phorbol 12-myristate 13-acetate
      (PMA); the inhibitory effect was decreased in hepatocytes from mature adult and
      senescent rats. In conclusion, our results favor the idea that a Ca(2+)-dependent
      and a Ca(2+)-independent, insulin-sensitive pathway remain involved throughout
      the life span. We provided the evidence for an impaired regulatory role of
      protein kinase C and calcium in hepatocytes from the older age groups.

PMID- 8282972
TI  - Alpha 1-adrenergic and arginine vasopressin stimulation of inositide hydrolysis
      in rat hepatocytes is unaltered in senescence.
AB  - Alpha 1-adrenergic receptors in the liver support glucose counterregulation by
      stimulating glycogenolysis and gluconeogenesis. We have recently reported that
      senescence is accompanied by reductions both in the density of alpha 1 receptors
      in liver homogenates and in the affinity of these receptors for agonists (Borst
      and Scarpace, 1990a). The present studies were undertaken to determine what
      consequences these reductions may have for agonist-stimulated second messenger
      production. To this end we measured the density of alpha 1-adrenergic receptors
      and agonist-stimulated phosphoinositide (PI) hydrolysis in short-term hepatocyte
      cultures derived from young and senescent rats. Receptor density in hepatocytes
      was unchanged with age. PI hydrolysis response to epinephrine was alpha 1 in
      nature, as it was fully blocked by prazosin. The epinephrine response was
      unchanged with age, both in maximum response and in sensitivity. Similarly, the
      response to arginine vasopressin (AVP) was also unchanged with age.

PMID- 8282973
TI  - Intestinal cell respiration is influenced by animal age, strain, and feeding
      status.
AB  - The objectives of this study were to evaluate the influence of aging and the
      fasted vs fed state on substrate oxidation by jejunal and colonic cells in vitro,
      and to determine whether the effects of these factors would be influenced by rat
      strain. Young (4 mo) and aged (24 mo) male rats of the Fischer 344 (F344) and
      Fischer x Brown Norway (F x BN) strains were used either following a 48-hr fast
      or in the ad libitum fed state. On the morning of experimentation, cells were
      removed from segments of the jejunum and colon and aliquots of these suspensions
      were incubated in 5 mM concentrations of substrates containing trace quantities
      of 14C-labeled isotopes. Following 60 min of incubation, 14CO2 was collected and
      quantified to determine substrate oxidation. The oxidation of glucose, glutamine,
      and 3-hydroxybutyrate was studied in jejunal and colonic cells, and the oxidation
      of acetate and butyrate was studied in colonic cells only. Glucose oxidation by
      jejunal cells was lower when cells were taken from 48-hr fasted animals than from
      fed animals, but the feeding status of the animal did not significantly influence
      oxidation of other substrates by jejunal or colonic cells. Substrate oxidation
      was not different for the F344 vs F x BN strains when jejunal and colonic cells
      were taken from young animals. Differences due to rat strain became apparent in
      the aged animals, however, with oxidation of several substrates being higher for
      the aged F344 than for the aged F x BN animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8282974
TI  - Effects of age and anatomic site on preadipocyte number in rat fat depots.
AB  - Preadipocytes are cells which are capable of either replication or of
      differentiation into fat cells. As with other stem or progenitor cell types, the
      replicative capacity of preadipocytes declines with increasing age; however,
      little information about effects of age on preadipocyte cell number in vivo is
      available. We determined preadipocyte number in the perirenal and epididymal fat
      depots of 3-, 17-, and 27-month-old Fischer 344 rats in 23 experiments.
      Increasing age was not associated with a decrease in preadipocyte number; indeed,
      the number of preadipocytes increased in epididymal depots throughout maturation
      and senescence. Hence, the tenet that aging causes a decline in the size of stem
      cell or progenitor pools is not generalizable to all tissues, even if the cells
      exhibit reduced replicative capacity in culture.

PMID- 8282975
TI  - The effect of recovery from depression on preferences for life-sustaining therapy
      in older patients.
AB  - BACKGROUND: This study compared older veterans' preferences about life-sustaining
      therapy before and after treatment for depression in order to determine whether
      recovery from depression is associated with an increase in the desire for these
      interventions. METHODS: Medical inpatients over 65 years of age were eligible.
      Depressed subjects scored > 14 on the Geriatric Depression Scale and were
      independently diagnosed by a psychiatrist as depressed. A questionnaire
      quantified preferences regarding potentially life-sustaining interventions
      currently, and in four hypothetical scenarios of illness. RESULTS: Initial
      interviews were completed on 50 depressed and 50 nondepressed subjects. Within 6
      months, 34 (68%) depressed and 40 (80%) control subjects were reevaluated.
      Preferences did not change significantly from initial to final interview,
      regardless of whether subjects had recovered from depression or remained
      depressed. With the exception of cardiopulmonary resuscitation, however, control
      subjects' preferences were more stable than depressed subjects' choices.
      CONCLUSIONS: This study demonstrated that treatment of mild-to-moderate
      depression does not necessarily result in an increased desire for life-sustaining
      medical therapy. Because depressed patients exhibit less consistency in their
      preferences over time, we advise careful and repeated discussions with the
      depressed patient regarding these decisions.

PMID- 8282976
TI  - The Sickness Impact Profile for nursing homes (SIP-NH)
AB  - BACKGROUND: Valid, feasible measures of functional status are needed to evaluate
      the expanding nursing home population. This study attempts to increase relevance
      and reduce respondent burden of the Sickness Impact Profile (SIP) for nursing
      home residents while maintaining internal consistency and validity. METHODS: 231
      residents from one academic and four community nursing homes, aged > or = 60 with
      a Mini-Mental State Exam score > or = 11, were study participants. Nominal group
      process was used to identify items and/or categories for removal. Candidate items
      were those that: represented restrictions of the nursing home environment, had
      weak item-total score correlations, and/or made minimal contribution to category
      internal consistency. Reduction was constrained by: minimum correlation of r =
      .90 between SIP and Sickness Impact Profile for Nursing Homes (SIP-NH) scores,
      coefficients alpha that fell within 95% confidence regions about predicted alpha.
      Convergent and discriminant validity were evaluated with the Katz Activities of
      Daily Living, Physical Disability Index, Geriatric Depression Scale, and Folstein
      Mini-Mental State Exam. RESULTS: The SIP-NH contains 66 items, a 51.5% reduction.
      Correlations between the SIP-NH and SIP were: total score r = .98, Physical
      dimension r = .97, and Psychosocial dimension r = .97. Alpha coefficients all
      fell within the 95% confidence regions. The SIP and the SIP-NH did not differ in
      correlations with validating instruments. CONCLUSIONS: The SIP-NH reduces
      respondent burden and has acceptable internal consistency and external validity.
      Potentially useful for discriminatory and predictive purposes, responsiveness to
      change will require longitudinal evaluation.

PMID- 8282977
TI  - Muscle strength and fiber adaptations to a year-long resistance training program
      in elderly men and women.
AB  - BACKGROUND: To study the effects of resistance training on muscle strength and
      size in older people, we enrolled 8 men and 17 women (mean age 68.2 +/- 1 SEM)
      into a one-year exercise trial. METHODS: Subjects were randomly assigned to
      exercise or control groups. Muscle biopsies were obtained from 11 subjects (8
      exercisers/3 controls) at baseline and after 15 weeks; exercisers underwent
      another biopsy at 30 weeks. After testing maximum strength using the 1-RM method,
      the exercisers began a 12-exercise circuit (3 sets of 8 repetitions at 75% of 1
      RM), 3 times a week. The controls repeated the strength testing every 15 weeks.
      They were asked to continue usual activities and not to start any exercise
      program. RESULTS: With exercise, muscle strength increased, average increases
      ranging from 30% (hip extensors) to 97% (hip flexors). Strength increased rapidly
      over 3 months, then plateaued for the duration of the experiment. No strength
      changes were observed in sedentary controls. Cross-sectional area of type 1
      muscle fibers increased in exercisers by 15 weeks (29.4 +/- 1%, p < .02) and
      after 30 weeks (58.5 +/- 13.7%, p < .002) compared to baseline. Type 2 fiber area
      did not change at 15 weeks, but increased by 30 weeks of training (66.6 +/- 9.5%,
      p < .0002). CONCLUSIONS: These results suggest that prolonged moderate to high
      intensity resistance training may be carried out by healthy older adults with
      reasonable compliance, and that such training leads to sustained increases in
      muscle strength. These improvements are rapidly achieved and are accompanied by
      hypertrophy of both type 1 and type 2 muscle fibers.

PMID- 8282969
TI  - Neuroendocrine regulation of thyrotropin-releasing hormone (TRH) in the
      tuberoinfundibular system.
AB  - [...] It is now required to list each part needed for mucous excretion. They are
      two ducts in the brain substance, then a thin portion of membrane shaped as the
      infundibulum, then the gland that receives the tip of this infundibulum and the
      ducts that drive the mucus (pituita) from this gland to the palate and nares.
      [...] and I said that one (duct) [...] from the middle of the common cavity
      (third ventricle) descends [...] into the brain substance, and the end of this
      duct is [...] the sinus of the gland where the brain mucus is collected [...].

PMID- 8282978
TI  - Chronic conditions that lead to functional limitation in the elderly.
AB  - BACKGROUND: The role of chronic medical conditions in elderly persons' loss of
      functional abilities is intuitively important but not well defined. This analysis
      was designed to identify chronic medical conditions that lead to the development
      of severe functional limitation. METHODS: Functionally intact members of a
      multistage probability sample (n = 6,862) of all noninstitutionalized U.S.
      civilians age 70 years or older were interviewed in 1984. Based on data from the
      National Death Index and from follow-up telephone interviews in 1988 with
      survivors, subjects were classified as functionally intact, functionally limited
      (unable to perform one or more of seven essential activities), or decreased.
      RESULTS: After adjusting for the effects of exercise habits and demographic,
      socioeconomic, and psychosocial factors, we found that the best predictors of the
      development of functional limitation were cerebrovascular disease (OR = 2.14; 95%
      CL = 1.16, 3.98) and arthritis (OR = 1.51; 95% CL = 1.08, 2.11). The contribution
      of coronary artery disease also approached statistical significance (OR = 1.49;
      95% CL = 0.99, 2.27). CONCLUSION: In the future, the primary prevention or
      effective treatment of cerebrovascular disease, arthritis, and possibly coronary
      artery disease may produce a modest reduction in the incidence of severe
      functional limitation.

PMID- 8282979
TI  - Reach to grasp: changes with age.
AB  - This study provides the first known kinematic assessment of the reach-to-grasp
      movement in elderly subjects. Twelve subjects (aged 60-71) were compared to
      gender-matched younger subjects (aged 18-25). Subjects reached 35 cm to grasp
      either a small (0.7 cm) or a large (8 cm) diameter cylinder. Precision grip was
      naturally adopted for the small cylinder, and whole hand prehension for the large
      cylinder. The displacements of active infrared markers (wrist and hand) were
      recorded with an Optotrak system. Movement initiation time, movement duration,
      and kinematic parameters of the reach-and-grasp components were computed. Older
      subjects showed slower, longer movements with a prolonged approach phase.
      However, the patterning and coordination of this movement, with respect to the
      utilization of a precision grip or whole hand prehension, were similar for both
      groups. Subtle changes with age thus appear to reflect a strategy that develops
      to compensate for deterioration in other systems such as visual or
      proprioceptive.

PMID- 8282980
TI  - Self-control skillfulness and caregiver burden among help-seeking elders.
AB  - Self-control skills are coping responses that help to organize one's own behavior
      and to manage cognitive and emotional responses that disrupt ongoing, adaptive
      behavior. The concept of self-control is applied to the chronically stressful
      caregiving experience. The present study examined the relationship between
      caregivers' role-specific burden and their self-control skillfulness. Forty-four
      caregivers of cognitively impaired spouses were assessed. Demographic
      characteristics, psychiatric symptomatology, role-specific burden, functional
      impairment of their spouse, and dispositional self-control skillfulness were
      measured. Highly skillful caregivers reported lower burden, fewer memory and
      behavior problems for their care recipient, and fewer psychiatric symptoms than
      less skilled caregivers. Hierarchical multiple regression analyses revealed that
      self-control skillfulness was associated with caregiver burden net the effects of
      covariates including age, education, memory and behavior problems of the care
      recipient, and caregivers' psychological distress. Results suggest that self
      control skills may play an important role in caregiving and may help to explain
      why some caregivers adapt better than others to their role.

PMID- 8282981
TI  - Influence of letter size on age differences in letter matching.
AB  - We tested healthy young and older adults on a simultaneous presentation, letter
      matching task that varied letter size. The goal of the experiment was to
      determine if older adults' higher baseline level of internal noise would affect
      age differences in letter-matching performance as letter size was varied. The
      results indicated that both young and older adults evidenced "fast-same" effects
      for RT and "false-different" effects for errors. However, older adults (compared
      to young adults) showed a larger "false-different" effect for errors, and this
      effect was especially pronounced for smaller letter pairs. These results imply
      that older adults' higher baseline levels of internal noise result in these
      individuals setting "compromise criteria" that underestimate the impact of
      internal noise.

PMID- 8282982
TI  - Age differences in the interpretation of misaligned "You-Are-Here" maps.
AB  - "You-Are-Here" (YAH) maps, common in shopping malls and office buildings, are
      difficult to interpret if not aligned with their surroundings. Younger and older
      adults made direction decisions after viewing simple maps representing a
      university campus. YAH arrows were either upright and coordinated with viewer
      position or contra-aligned 180 degrees. Contra-alignment caused subjects,
      especially older adults, to take more time and be less accurate. Women were
      slower on contra-aligned maps, although no less accurate, than men. The need to
      mentally realign such incongruent maps in order to make correct direction
      decisions can cause serious difficulty for older adults trying to navigate
      through large, complex environments.

PMID- 8282983
TI  - Adult age differences in long-term memory for performed activities.
AB  - Participants in two studies conducted by Salthouse (in press) were called 2 to
      182 days after participation and asked to describe the activities that they had
      performed in the previous study. Hierarchical regression analyses were used to
      examine the prediction of activity recall from age, speed, and retention
      interval. Overall, age was associated with 20% of the variance in activity
      recall, and retention interval was associated with 19%, but there was no
      significant interaction of age and retention interval. When perceptual speed was
      entered into the regression equation before age, the age-related variance was
      reduced by 70%. A small, but statistically significant, amount of age-related
      variance in activity memory remained after controlling for speed and retention
      interval.

PMID- 8282984
TI  - Psychosocial correlates and sequelae of electroencephalographic sleep in healthy
      elders.
AB  - This research examines longitudinal data on psychosocial status and
      polysomnographic sleep collected annually from 57 healthy, community-residing
      elders aged 61-89. Cluster analysis of variables reflecting sleep continuity and
      architecture at the baseline assessment was used to identify three groups of
      elders: those whose sleep was either (a) superior to all remaining respondents
      across a variety of measures, (b) marred only by significantly reduced sleep
      efficiency relative to other respondents, or (c) poorer than all other
      respondents in multiple areas. Cross-validation procedures suggested that the
      three-group cluster solution was stable and replicable over persons and over
      time. Subsequent multivariate analyses indicated that recent life events, as well
      as psychosocial stability and support variables at baseline, distinguished
      between the sleep pattern groups. Moreover, sleep pattern group membership itself
      predicted subjects' subsequent sleep characteristics and psychosocial status at
      follow-up. Implications of these results for conceptualizing psychosocial factors
      that affect, and are ultimately affected by, sleep disturbances in late life are
      discussed.

PMID- 8282985
TI  - Changes in sources of community long-term care among African American and white
      frail older persons.
AB  - This study examined race differences in changes in source of long-term care. We
      addressed the following questions: (1) Are there differences between African
      Americans and Whites in the patterns of transitions among community longterm
      care, institutionalization, and death? (2) Are there differences between African
      American and White populations in sociodemographic characteristics and functional
      limitations influencing source of long-term care in a two-year follow-up sample?
      (3) Controlling for socioeconomic status, health status, level of informal care,
      and demographic variables, are there differences between African Americans and
      Whites in patterns of change to informal and mixed (informal and formal) care
      among community-dwelling frail older persons? and, (4) What are the predictors of
      change patterns within African American and White populations of older frail
      persons? The source of data is the longitudinal component of the 1982-1984
      National Long Term Care Survey (NLTCS). Results of multinomial logistic analysis
      indicate few differences in change patterns, despite differences in the context
      of care among African American and White frail older persons.

PMID- 8282986
TI  - Informal support and the use of formal services by older Americans.
AB  - Older persons' use of formal services was studied in the context of one medium
      sized metropolitan area in the Northeast, with a principal focus on the relation
      between formal service use and informal help. Most services are used by only a
      minority of older persons. There is some evidence of both compensatory processes
      (where family support substitutes for formal care) and bridging (where the
      informal network helps link the older person to services). Service users are
      distinguished partly by their greater functional disability. Use of some services
      is affected by indicators of predisposition, such as sociability and age
      identity. Enabling factors, such as availability of services or their
      accessibility by the respondent, have little effect.

PMID- 8282987
TI  - Social networks, social support, and mortality among older people in Japan.
AB  - This study examined the effects of social networks and social support on the
      mortality of a national probability sample of 2,200 elderly Japanese persons
      during a three-year period. The direct and indirect effects of social
      relationships were assessed by using hazard rate models in conjunction with
      ordinary least squares regressions. Among the five measures of social
      relationships, social participation is shown to have a strong impact on
      mortality, and this effect remains statistically significant when other factors
      are considered. Social participation, social support, and feelings of loneliness
      are found to have indirect effects on the mortality of the Japanese elders
      through their linkages with chronic diseases, functional status, and self-rated
      health. On the other hand, marital status and social contacts are not shown to
      have statistically significant effects on the risk of dying, either directly or
      indirectly.

PMID- 8282988
TI  - Physical, psychological, and social resources as moderators of the relationship
      of stress to mental health of the very old.
AB  - The purpose of this pilot study was to assess the attenuating effects of
      physical, psychological, and social resources on the relationship between stress
      and mental health among the oldest old. Physical resources include perceived
      health and independence in functional and instrumental activities of daily
      living, while psychological resources include mastery, self-esteem, and coping.
      Social resources are measured by frequency of social interaction and size of the
      social network. Among the 124 women and 31 men (M = 89 years), greater
      independence in IADLs and greater perceived control of events significantly
      attenuated the adverse effects of strain on psychological well-being.

PMID- 8282989
TI  - Comparison of mental status tests: implications for Alzheimer's patients and
      their caregivers.
AB  - Most existing measures commonly used to determine cognitive dysfunction in
      demented persons exclude important pieces of information. In an effort to address
      this deficiency, many Alzheimer's disease programs have combined items from the
      Blessed Information, Orientation, Memory and Concentration Test with those of the
      more established Mini-Mental State Exam. While the expansion may be clinically
      helpful, results are typically presented in the form of summary scores that
      ignore the issue of multidimensionality. Drawing upon data from 201 elderly
      patients afflicted with Alzheimer's disease and their adult child caregivers,
      this study examined the factorial structure of the combined Blessed Folstein
      Instruments. The factor-derived scores are compared with summary scores in terms
      of their association with functional status of the patients and with caregiver
      stress and burden.

PMID- 8282990
TI  - Is the time finally ripe? Health insurance reforms in the 1990s.
AB  - Reformers feel certain that the time is now ripe for progressive legislation to
      ensure universal citizen access to health insurance and to contain rising costs
      in the health care industry. But history shows us that reformers were equally
      confident in earlier periods of modern U.S. history, only to find themselves
      defeated by conservatives willing to deploy ideological, emotionally charged
      arguments against government-sponsored reforms. Today's advocates of inside-the
      beltway bargains for hammering out compromise reforms may be vulnerable to
      similar conservative counterattacks. Reformers need to engage the U.S. citizenry
      as a whole in democratic discussion about the ideals of government-sponsored
      health care reforms. Advocates of single-payer plans can do this more readily
      than supporters of complex public-private schemes such as play or pay or managed
      competition, but all those who want inclusive and effective reforms during the
      1990s must face the challenge of democratic dialogue.

PMID- 8282991
TI  - Is health care different? Popular support of federal health and social policies.
AB  - Over the past several years there has been a striking increase in policymakers'
      attention to health care reform. This paper explores whether there has been a
      corresponding shift in popular attitudes and identifies factors that may have
      changed these attitudes. The first part of the analysis relies on survey data
      collected between 1975 and 1989 to estimate a set of regression models, relating
      support for federal involvement in health care, antipoverty programs, and general
      domestic policies to a set of sociodemographic characteristics. Relative to other
      federal policies, support for health initiatives grew over this period. During
      the same period, long-standing differences in support between rich and poor, old
      and young, educated and uneducated, all narrowed for health care, though they did
      not for other types of federal policies. The second part of this study explores
      motivations that might account for these patterns. We identify a half dozen ways
      in which health care may be viewed as "different," that is, more or less
      appropriate for federal action. Analysis of survey data from 1987 suggests that
      there are relatively small differences in the attitudes and perceptions that
      motivate support for federal health initiatives, relative to federal domestic
      policies in general. However, there are more striking differences between health
      programs and more overtly redistributive policies. Compared to redistributive
      federal programs, support for federal health initiatives are (a) less identified
      with racial minorities or economically disadvantaged groups, (b) less constrained
      by notions of individual responsibility, (c) more closely associated with
      concerns about equal opportunity in American society, and (d) somewhat more
      constrained by choices between federal and local government. These patterns
      persist whether or not respondents are politically active and whether they report
      themselves to be liberal or conservative. We suggest that the growing support for
      federal intervention in health care, relative to other social policies, is in
      part an inadvertent by-product of ideological positions popularized during the
      Reagan and Bush administrations. We draw from these results some predictions
      about the course of the ongoing debate over federal health policies.

PMID- 8282992
TI  - Health reform impasse: the politics of American ambivalence toward government.
AB  - This paper presents two interrelated arguments: it rethinks conventional
      understanding of the policy-making process and analyzes an important substantive
      issue regarding public opinion. The substantive issue involves the public's deep
      ambivalence toward government reforms: Americans are simultaneously supportive of
      significant reform and uneasy about expanding government involvement. The
      critical question is what, if any, impact this public ambivalence will have on
      policy deliberations. Answering this question requires an analysis of the role of
      public opinion in policy-making. Investigation of historic as well as
      contemporary health reform suggests that the impact of public opinion varies,
      depending on the character of both public opinion and the policy issue. The
      public's preferences are not especially influential when they are characterized
      by uncertainty or when an issue is not salient, but strong and sustained
      sentiment can affect agenda setting, interest group leverage over government
      officials, and policymakers' formulation of detailed administrative arrangements.

PMID- 8282993
TI  - Can an employer-based health insurance system be just?
AB  - It is America's distinctive practice to tie private health insurance to
      employment, and recent proposals have tried to retain this link through mandating
      that all employers provide health insurance to their employees. My primary
      approach to these issues is neither economic, nor historical, nor political but
      ethical. After a brief historical overview, I outline a general approach to
      evaluating the ethical significance of linking the distributions of distinct
      goods. I examine whether an unjust distribution of jobs spoils justice in the
      distribution of health insurance, taking as a central example gender inequities
      in employment and exploring their impact on job-based health insurance. Second, I
      explore the possibility that justly awarding jobs guarantees justice in
      employment-sponsored insurance. However, linking the distributions of different
      goods remains problematic, because such links inevitably undermine equality by
      enabling the same individuals to enjoy advantages in many different distributive
      areas. Finally, I examine recent proposals to reform America's health care system
      by requiring all employers to provide health insurance to their employees. I
      argue that such proposals lend themselves to the same ethical problems that the
      current system does and urge greater attention to alternative reform options.

PMID- 8282994
TI  - Revisiting the employment-insurance link.

PMID- 8282995
TI  - The pragmatic appeal of employment-based health care reform.

PMID- 8282996
TI  - Universal health insurance that really works: foreign lessons for the United
      States.
AB  - The United States has serious and worsening problems in the delivery and
      financing of health. The debate about reform has inspired many schemes that are
      persuasive in their presentation, but they are unrealistic: some cannot be
      enacted by Congress, others would not improve existing arrangements, most are
      imaginary inventions with uncertain outcomes. The most politically prudent and
      the most effective course is to emulate the methods used successfully and
      available for full analysis in other developed countries. America created its
      successful social security system in this fashion, and statutory health insurance
      should be added now. All or most groups would be required to join. Financing
      would come from social security payroll taxes, supplemented by government
      subsidies. Basic acute care services would be equally available to all. The
      existing insurance companies would remain as fiscal intermediaries. Doctors and
      hospitals would continue to work much as they do now. They would prosper from
      more utilization, few bad debts, and less administrative trouble. The payment and
      work of doctors would be governed by collective negotiations between the
      insurance carriers and the medical associations. The payment and work of
      hospitals would be governed by a mixture of government regulations and
      negotiations with the carriers. Costs would be controlled by coordinated decision
      making by the payers, the providers, and government. The system would not turn
      over services and financing to government.

PMID- 8282997
TI  - The health care bureaucracy: small changes, big consequences.
AB  - Administrative changes have been reshaping health policy for the past decade. One
      consequence is a more constrained medical profession. Another is a more powerful
      health care bureaucracy. Most industrialized nations have called on democratic
      principles to balance professional norms; in contrast, Americans are developing a
      distinctly bureaucratic health care regime. This article suggests why and
      explores the ramifications for both the politics of health care and the practice
      of medicine.

PMID- 8282998
TI  - From community health care to crisis medicine: have we learned the right lessons?

PMID- 8282999
TI  - Health care reform and race-specific policies.

PMID- 8283000
TI  - Population-based health care for communities.

PMID- 8283001
TI  - Lessons from the frozen North.

PMID- 8283002
TI  - The mechanisms of aspirin-induced gastric mucosal injury.
AB  - We examined changes in intracellular pH with the fluorescent probe BCECF after
      treatment with aspirin (ASA) in gastric mucosal cells isolated from guinea pigs
      at various extracellular, pH levels. The cytotoxic activities of ASA and the
      intracellular trapping of ASA at various extracellular pH levels were also
      examined by colorimetric MTT assay and counting the influx of [14C](carboxyl-14C)
      ASA. Under acid extracellular pH, ASA reduced intracellular pH in gastric mucosal
      cells and exhibited cytotoxicity. Intracellular trapping of ASA was also observed
      only under acidic extracellular conditions. The present study suggests that ASA
      causes gastric mucosal cell injury in vitro by reducing intracellular pH,
      resulting from intracellular trapping of ASA under acidic extracellular
      conditions.

PMID- 8283003
TI  - Epidermal growth factor protects gastric mucosa against ischemia-reperfusion
      injury.
AB  - Epidermal growth factor (EGF) protects gastric mucosa against many injurious
      factors, but no study has examined whether EGF may protect against ischemia
      reperfusion (I-R)-induced gastric mucosal injury. We assessed the effect of EGF
      pretreatment on the extent of ischemia-reperfusion-induced gastric mucosal damage
      in rats. Assessment of injury and protection included: the extent of macroscopic
      necrosis; qualitative and quantitative histology with measurement of deep mucosal
      necrosis; microvascular permeability after injection of fluorescein-conjugated
      albumin; and transmission electron microscopy. After I-R, saline-pretreated rats
      (placebo group) had macroscopic necrosis involving 40 +/- 6% of total gastric
      mucosal area. Histology revealed exfoliation of the surface epithelial cells,
      mucosal hemorrhages, microvascular injury, and extensive deep mucosal necrosis
      involving 7 +/- 5% of mucosal strips. Microvascular permeability assessed by
      fluorescein-conjugated albumin was significantly increased to 327 +/- 29% of that
      in normal rats (without ischemia-reperfusion). Transmission electron microscopy
      showed severe microvascular injury. EGF pretreatment significantly reduced gross
      mucosal necrosis to 17 +/- 6% and deep histologic mucosal necrosis to 2 +/- 1%
      (both p < 0.01 versus saline pretreated). Integrity of the mucosal microvessels
      was preserved and microvascular permeability was close to normal. This study
      demonstrates that EGF significantly reduces ischemia-reperfusion injury to the
      rat gastric mucosa and that this effect of EGF may be mediated by its protection
      of the mucosal microvessels.

PMID- 8283004
TI  - Role of leukotrienes in indomethacin-induced mucosal damage in rats.
AB  - The role of leukotriene (LT) in the pathogenesis of indomethacin-induced gastric
      mucosal damage was investigated in rats. After administration of indomethacin,
      LTB4 and sulfidopeptide LT (SPLT) content in gastric mucosa were assessed by
      radioimmunoassay and mucosal blood flow was measured by laser-Doppler flowmetry.
      Indomethacin (20 mg/kg) caused visible gastric mucosal damage. Indomethacin at
      this dose caused marked reduction of gastric mucosal blood flow but did not
      affect gastric mucosal content of LTB4 and SPLT. AA-861, a selective 5
      lipoxygenase, and DS-4575 and YM-683, two different SPLT receptor antagonists,
      inhibited both mucosal damage and reduction of mucosal blood flow. These results
      suggested that endogenous LT, especially SPLT, may be involved in the
      indomethacin-induced mucosal damage via the reduction of gastric mucosal blood
      flow.

PMID- 8283005
TI  - Effect of sofalcone on gastric mucosal injury induced by ischemia-reperfusion and
      its antioxidant properties.
AB  - The effect of sofalcone on gastric mucosal injury induced by ischemia-reperfusion
      (I-R) injury was studied in rats. I-R injury was produced in rat stomach by
      applying a small clamp to the celiac artery for 30 min and by removal of the
      clamp for 60 min. The increase in total area of erosions in the stomach after I-R
      and the increase in lipid peroxides in the gastric mucosa were significantly
      inhibited by intragastric administration of sofalcone. In addition, sofalcone
      significantly inhibited the lipid-soluble free radical initiator-induced increase
      in lipid peroxides of the gastric mucosal homogenate, and could show scavenging
      action of superoxide radicals in aprotic solvent. These results showed that the
      protective effect of sofalcone against I-R-induced gastric mucosal injury is
      attributable to its antioxidant activities in the lipophilic phase.

PMID- 8283006
TI  - Effects of transforming growth factor alpha and beta on rabbit gastric epithelial
      cell proliferation: a preliminary report.
AB  - The effects of epidermal growth factor (EGF), transforming growth factor alpha
      (TGF alpha), insulin-like growth factor-I (IGF-I), and transforming growth factor
      beta (TGF beta) on tritiated thymidine incorporation into DNA by rabbit gastric
      epithelial cells were investigated. EGF, TGF alpha, and IGF-I at concentrations
      of 10(-10) and 10(-9) M all produced a serum-like stimulatory effect, whereas TGF
      beta at both concentrations was inhibitory. Coadministration of TGF alpha had no
      additional effect on EGF-stimulated tritiated thymidine incorporation into DNA.
      On the other hand, coadministration of TGF beta abolished EGF-stimulated
      tritiated thymidine incorporation into DNA, suggesting possible interactions
      between the two growth factors.

PMID- 8283007
TI  - Rapid repair of the surface epithelium in human gastric mucosa after acute
      superficial injury.
AB  - Morphologic changes associated with rapid epithelial repair in human gastric
      mucosa were examined by light and transmission electron microscopy in samples
      obtained at biopsy. A timed series of samples covering six intervals (3-30 min)
      after exposure to 50% (vol/vol) ethanol was available. Samples exposed to 25%
      ethanol and to acidified sodium taurocholate were also studied. Changes
      indicative of epithelial repair were first seen in samples fixed 15 min after
      ethanol. In samples fixed 30 and 45 min after exposure to barrier breakers, there
      were widespread changes indicative of epithelial repair. We have tentatively
      identified three morphologically distinct types of repair: lateral movement of
      the epithelial cell basal plasma membrane, which maintains close contact with the
      basal lamina and which may occur only in the presence of continued vascular
      perfusion; migration of shortened, cuboidal cells with blunt pseudopods and
      lamellipodia. This morphology predominated over sites of vascular congestion; and
      the formation of epithelial arches in which the epithelial cells did not make
      contact with the underlying basal lamina. Rapid repair by cell migration was
      observed only at sites in which a grossly intact basal lamina was present.

PMID- 8283008
TI  - Lipid analysis of Helicobacter pylori.
AB  - Lipids from Helicobacter pylori were extracted, isolated by conventional DEAE
      Sephadex and silica gel column chromatography, and then purified by preparative
      thin-layer chromatography. Simple and phospholipids were analyzed by HPTLC and
      quantitatively determined by densitometry scanning. The fatty acid compositions
      of simple lipids were estimated by gas-liquid chromatography. The simple lipid
      composition of H. pylori consisted of wax ester (2.5%), triglycerides (4.9%),
      free fatty acids (30.0%), cholesterol (6.9%), diacylglycerol (29.1%), and
      monoacylglycerol (2.6%). The neutral phospholipid composition consisted of
      phosphatidyl ethanolamine (79.1%), lysophosphatidyl ethanolamine (16%), and
      phosphatidyl choline (1.9%). That of acidic phospholipids consisted of
      phosphatidic acid (52.7%) and phosphatidyl serine (47.3%). The major fatty acids
      of crude lipid, wax, free fatty acids, triglycerides, diacylglycerides, and
      monoacyl glycerides were C19:1 (cyclo), C18:2, C16:0, C19:1 (cyclo), C22h:0, and
      C18:0, respectively. These results are new findings and suggest significant
      characteristics from the metabolic, physiologic, and chemotaxonomic point of
      view.

PMID- 8283009
TI  - Implications of nitric oxide in the action of cytoprotective drugs on gastric
      mucosa.
AB  - Cytoprotective drugs, including sucralfate, colloidal bismuth (De-Nol), aluminium
      containing antacids (Maalox), carbenoxolone-like agents (sofalcone), and stable
      PGE2 analogues (nocloprost), are known to prevent acute gastric mucosal damage
      induced by topical irritants. This effect is usually accompanied by an elevation
      in mucosal blood flow. Recently, nitric oxide (NO), a potent vasorelaxant, has
      been implicated in gastroprotection by carbenoxolone, the prototype of
      cytoprotective drugs. In this study we assessed the involvement of NO in acute
      gastric damage induced by ethanol and in the prevention of this damage by
      sucralfate, Maalox, De-Nol, sofalcone, and nocloprost. Each of these drugs dose
      dependently reduced the formation of ethanol-induced gastric lesions. The optimal
      gastroprotective dose was used in further studies to check the possible
      contribution of NO in this protection. Pretreatment with NG-nitro-L-arginine (L
      NNA) (12.5-50 mg/kg i.v.), an inhibitor of NO synthase, dose-dependently enhanced
      the mucosal damage by ethanol itself and reduced the protective effects of
      sucralfate and Maalox but not those of sofalcone, De-Nol or nocloprost against
      the ethanol injury. Reduction by L-NNA of the mucosa-protective action of
      sucralfate or Maalox was accompanied by a decrease in gastric blood flow, which
      was antagonized by L-arginine (a substrate of NO synthase) but not by D-arginine.
      This study suggest that gastroprotective agents such sucralfate and Maalox, but
      not sofalcone or De-Nol, activate the NO system that may contribute to mucosal
      integrity and preservation of mucosal microcirculation.

PMID- 8283010
TI  - Significance of serum markers pepsinogen I and II for chronic atrophic gastritis,
      peptic ulcer, and gastric cancer.
AB  - Chronic atrophic gastritis (CAG) is closely correlated with gastric cancer and is
      predominant in Japan. Epidemiologically, food habits are the primary factor in
      both CAG and gastric cancer. Two potential serum markers for CAG have recently
      been investigated, i.e., the concentration of serum pepsinogen (PG) and the
      presence of serum antibodies against Helicobacter pylori. Serum PG I and II and
      the PG I:PG II ratio have been reported to be useful as indicators of recurrent
      peptic ulcer and for screening of patients at risk from gastric cancer. In this
      study, we examined PG I and II in serum from 483 patients by RIA (DAINABOT), and
      endoscopic examination performed in the same patients before serological assay
      revealed CAG in 68, peptic ulcer in 91, and gastric cancer in 48. Analysis of the
      mean values according to patients age showed that CAG patients in their forties
      to eighties had low (< 40 ng/ml) levels of PG I, peptic ulcer patients in their
      teens to eighties had high (> or = 70 ng/ml) levels, except for those in their
      seventies, and gastric cancer patients in their twenties to sixties had low (<
      3.0) PG I:PG II ratios, except for those in their sixties. Thus serum PG assay
      has potential utility for detection of CAG, peptic ulcer, and gastric cancer.

PMID- 8283011
TI  - Increased chemiluminescence and ulcer development in the low blood flow state of
      the gastric tube for esophageal replacement.
AB  - Peptic ulcers in the gastric tube for esophageal replacement develop in spite of
      reduction of acid secretion after truncal vagotomy and often result in serious
      conditions such as bleeding and perforation. Thirteen cases of gastric tube
      ulcers were detected endoscopically from 1985 to 1990 in our hospital. Most of
      these ulcers developed within 20 cm of the anastomosis (esophagogastrostomy),
      which was an especially hypoxic and ischemic area. Ischemic change due to
      decreased blood supply is suggested as a causative factor in ulcer development.
      Recent studies indicate that chemiluminescence (ChL) activity may increase even
      in the low-flow hypoxic condition. Therefore, we investigated the ChL of regional
      blood in the hypoxic gastric tube in dogs. The ChL activity of the blood sample
      collected from the ischemic region in the gastric tube significantly increased
      after construction of the gastric tube, compared with systemic blood from the
      femoral vein, and the number of leukocytes decreased in the ischemic region. We
      believe that oxygen radicals derived from neutrophils adhering to the vascular
      endothelium may play an important role in the damage to endothelial cells of the
      gastric tube and suggest the possibility of their causative effects in the
      process of ulcer formations.

PMID- 8283012
TI  - Effects of intracerebroventricular injection of indomethacin on adaptive gastric
      cytoprotection in the conscious rat.
AB  - We investigated the role of prostaglandins in the central nervous system for the
      adaptive gastric cytoprotection in male Wistar rats with chronic
      intracerebroventricular cannulas. Three, 50, 200, or 500 micrograms of
      indomethacin or vehicle alone was injected via the intracerebroventricular
      (central) or intraperitoneal route 1 h before oral administration of 20% ethanol.
      The animals were then given 1 ml of absolute ethanol 15 min later. One hour
      later, gastric mucosal damage and plasma indomethacin concentrations were
      measured. Pretreatment with 50-500 micrograms of indomethacin abolished adaptive
      gastric cytoprotection induced by 20% ethanol in a dose-dependent fashion,
      regardless of the route of administration. Central administration of 3 micrograms
      indomethacin resulted in a more than twofold increase in mucosal damage compared
      with intraperitoneal administration. Plasma indomethacin concentrations were
      increased dose-dependently. However, plasma levels were lower in rats
      administered centrally than those peripherally at a dose of 50 micrograms
      indomethacin or more. On the other hand, plasma indomethacin concentrations did
      not differ between central and intraperitoneal administration of 3 micrograms
      indomethacin. Measurement of gastric mucosal blood flow revealed that central
      administration of 3 micrograms indomethacin reduced gastric mucosal blood flow,
      whereas intraperitoneal administration of an identical dose had no effect. These
      results suggest that central prostaglandins may contribute to adaptive gastric
      cytoprotection, possibly by altered gastric mucosal blood flow.

PMID- 8283013
TI  - Regulation of gastroduodenal bicarbonate secretion by capsaicin-sensitive sensory
      neurons in rats.
AB  - We investigated the role of capsaicin-sensitive sensory neurons in regulation of
      gastroduodenal HCO3- secretion in anesthetized rats. The stomach (under acid
      inhibition by omeprazole 60 mg/kg i.p.) or the duodenum was perfused with saline
      (pH 4.5) and HCO3- output was determined by pH change in the perfusate. Both the
      duodenum and stomach responded to prostaglandin E2 (PGE2; 300 micrograms/kg i.v.)
      or luminal acid by a significant increase in pH and HCO3- output. These tissues
      also responded to luminal application of capsaicin (0.3-6 mg/ml for 30 min),
      resulting in a significant increase of pH and HCO3- output in a concentration
      related manner. The HCO3- stimulatory action of capsaicin was markedly attenuated
      by functional ablation of capsaicin-sensitive sensory neurons, significantly
      mitigated by indomethacin, and exhibited tachyphylaxis after repeated application
      at a high concentration. The acid-induced pH and HCO3- responses were also
      significantly mitigated by sensory deafferentation and by indomethacin, whereas
      those induced by PGE2 remained unaffected. In addition, defunctionalization of
      these sensory nerves resulted in macroscopically visible damage in the duodenum
      when acid secretion was concomitantly stimulated by histamine. We conclude that
      capsaicin-sensitive sensory neurons may be involved in the regulatory mechanism
      of gastroduodenal HCO3- secretion and contribute to protection of the mucosa
      against acid. Endogenous PGs may be involved in the HCO3- stimulatory action
      mediated by capsaicin-sensitive sensory neurons.

PMID- 8283014
TI  - Binding sites for calcitonin gene-related peptide in regenerating gastric mucosa.
AB  - To clarify the effector sites and significance of calcitonin gene-related peptide
      (CGRP) in the gastric mucosa, the specific binding sites of CGRP in the rat
      stomach were studied with autoradiography of soluble compounds and in vitro
      autoradiography. Binding sites for CGRP in the stomach were seen on the vascular
      smooth-muscle cells of the arterioles and venules, on the nonvascular smooth
      muscle cells of the muscularis mucosae, and on the longitudinal layer of the
      muscularis propriae. After acetic acid treatment, the number of silver grains was
      significantly increased in the regenerated mucosa. These data support the
      significant role of CGRP in the regulation of cytoprotection of the stomach
      through an increase in the microcirculatory blood flow and through extended
      smooth-muscle relaxation.

PMID- 8283015
TI  - Mucosal secretion and cytoprotection of the rat gastric mucosa.
AB  - We carried out a series of experiments to test the hypothesis that many examples
      of gastric cytoprotection result from the ability of protective agents to elevate
      mucosal secretion. Specifically, such protection would be effective against
      barrier breakers that act directly on the mucosal surface. We have previously
      observed that the protection found to result, in our rat gastric chamber model,
      from luminal stasis or from sucralfate, was accompanied by increases in the
      thickness of a juxtamucosal pH gradient. The pH gradient was measured with
      antimony microelectrodes and was about 900 microns thick over chambered gastric
      mucosae that had not had the luminal solution stirred for at least 5 min. When
      the solution was stirred (200 rpm) for 10 min with a plastic paddle, the
      thickness of the pH gradient was decreased to about 400 microns but recovered to
      more than 90% of the starting value within 5 min. The thickness of the pH
      gradient varied from site to site, with a range from about 500 microns to 1,800
      microns. However, the thickness was constant at a given site when it was
      remeasured after about 1 h. Capsaicin at a concentration of 640 microM rapidly
      increased both gastric blood flow and the thickness of the juxtamucosal pH
      gradient by about 50%. However, 25 min after removal of the capsaicin the gastric
      blood flow approached pre-capsaicin levels, and the thickness of the gradient
      remained increased by nearly 50%. In a third set of experiments, the
      vulnerability of specific sites on the chambered mucosae to acidified sodium
      taurocholate was correlated with the thickness of the juxtamucosal pH gradient
      before exposure to taurocholate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283016
TI  - Central action of TRH to induce vagally mediated gastric cytoprotection and ulcer
      formation in rats.
AB  - The vagus nerve plays an important role in gastric cytoprotection and gastric
      lesion formation, but the central and peripheral mechanisms by which the vagus
      mediates these dual effects on the gastric mucosa are still not well established.
      Recent evidence indicates that the tri-amino acid peptide thyrotropin-releasing
      factor (TRH) acts in the brain, most likely in the dorsal vagal complex, and
      stimulates gastric vagal efferent discharges. Such increased vagal activity
      results in cholinergic stimulation of the gastric secretory and motor functions
      that influence the resistance of the gastric mucosa to injury. Low doses of TRH
      or its stable analogue, RX 77368 (0.5-1.5 ng), injected into the cisterna magna,
      confer cytoprotection against ethanol-induced gastric lesions through the vagal
      cholinergic stimulation of gastric prostaglandin release. After higher doses of
      RX 77368 (3-300 ng), cytoprotection is observed only when the associated increase
      in acid secretion is prevented by omeprazole. Intracisternal injection of RX
      77368 at doses of 1-3 micrograms induces the development of acute gastric lesions
      within 4 h which are further enhanced by indomethacin in fasted rats. Gastric
      lesions are related to the vagally mediated sustained increase in gastric acid
      and pepsin secretion, motility, and vascular changes. These data, added to the
      neuroanatomic evidence of high concentrations of TRH fibers and receptors in the
      dorsal vagal complex, indicate that medullary TRH may play an important role in
      the central vagal regulation of gastric mucosal resistance. This mucosal
      resistance is influenced by the interaction between vagal-cholinergic activation
      of cytoprotective mechanisms (prostaglandin, increased gastric mucosal blood
      flow) and ulcerogenic factors (histamine, acid, pepsin, motility).

PMID- 8283017
TI  - The relationship between endoscopic findings of gastric ulcer scar and ulcer
      relapse.
AB  - Regenerated mucosal patterns that appeared during the healing of chronic gastric
      ulcers were observed and assessed in detail by magnifying endoscopes. Three
      patterns of ulcer scarring were distinguished: Sa with central depression, Sb
      with a coarse regenerated mucosal pattern, and Sc with a fine mucosal pattern.
      From a study on the relationship between the depth of ulcer confirmed
      histologically and the endoscopic findings of the scar, a clear distinction could
      be made endoscopically between U1-IV scar with a well-demarcated scarring zone,
      U1-III scar with an unclear boundary, and U1-II scar without a distinct scar
      area. Scar patterns were also related to ulcer depth. Analysis of the
      relationship between an ulcer relapse and the scar pattern demonstrated that the
      ulcer relapse rate over a 2-year follow-up period was 84% in Sa, 33% in Sb, and
      0% in Sc.

PMID- 8283018
TI  - Apoptosis: genetically programmed physiologic cell loss in normal gastric oxyntic
      mucosa and in mucosa of grossly healed gastric ulcer.
AB  - Maintenance of gastric mucosal structure depends on a dynamic balance between
      cell loss and cell renewal. The surface epithelial cells exfoliate at a rapid
      rate (usually in response to luminal contents) and are entirely replaced within 3
      5 days. The loss of parietal, chief, and endocrine cells is much slower, but
      there is little information concerning the morphologic aspects of this process.
      Because in other tissues cells are physiologically eliminated through a process
      of apoptosis--genetically programmed cell self-destruction and loss--we studied
      whether this process occurs in normal gastric mucosa and in the mucosa of
      recently healed gastric ulcers in the rat. Degeneration and loss of the surface
      epithelial cells into the gastric lumen occurs in normal oxyntic mucosa, and more
      extensive desquamation of poorly differentiated mucous cells in the dilated
      gastric glands takes place within mucosal scars of grossly healed gastric ulcers.
      Apoptosis of parietal, chief, and endocrine cells in normal oxyntic mucosa and
      apoptosis of poorly differentiated cells lining dilated glands in mucosal scar
      were assessed and characterized by electron microscopy. Apoptosis affects single
      glandular cells and involves a rapid initial condensation of both nucleus and
      cytoplasm, with subsequent fragmentation. Finally, the cell is converted into a
      cluster of membrane-bound apoptotic bodies, which usually are engulfed by
      adjacent cells or disposed into a glandular lumen. Desquamation of surface
      epithelium and apoptotic self-destruction of glandular epithelium stimulate a
      constant cell renewal and thus contribute to the maintenance of the ulcer healing
      process. Rapid and "excessive" proliferation of regenerating gastric epithelium
      enables re-epithelialization of ulcer crater.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283020
TI  - Age-related changes in the microvessels of the human stomach: an ultrastructural
      study.
AB  - The ultrastructure of microvessels in the gastric mucosa of patients with
      atrophic gastritis was investigated. In the gastric mucosa of atrophic gastritis,
      the endothelial cells of microvessels were irregularly swollen and subendothelial
      spaces were enlarged. The basement membrane underlying the endothelium was
      thickened. Degeneration of smooth-muscle cells was also evident in the media.
      These changes appear to correspond to sclerosis or aging of the microvessels.
      Such sclerotic changes in microvessels may initiate deterioration of the
      microenvironment in the gastric mucosa and may consequently affect metabolic
      activity of the gastric mucosal cells. Those sequences might induce degeneration
      or abnormal differentiation of mucosal cells. Such vascular changes may advance
      slowly and increase in intensity with advancing age. The final result would be
      the histologic changes associated with atrophic gastritis.

PMID- 8283019
TI  - Trefoil peptide gene expression in small intestinal Crohn's disease and dietary
      adaptation.
AB  - We examined the patterns of trefoil peptide gene expression in the ulcer
      associated cell lineage (UACL) and mucosa adjacent to Crohn's disease in humans
      and during gastrointestinal adaptation to enteral feeding in rats. In the UACL,
      human spasmolytic polypeptide (hSP) mRNA and peptide are present in the acinar
      and proximal duct cells, whereas pS2 mRNA and peptide are found in the distal
      duct cells and in the surface cells. In mucosa adjacent to UACL, pS2 mRNA and
      peptide are expressed ectopically by goblet cells and neuroendocrine cells.
      Intestinal crypts associated with the UACL showed marked neuroendocrine cell
      hyperplasia. Ultrastructural immunolocalization showed pS2 to be copackaged in
      the mucous cell and neuroendocrine granules. The copackaging of a secretory
      protein in both mucous and neuroendocrine granules, which have different
      functions, is unusual and indicates an important role for pS2 in the secretory
      process itself or as a ligand delivered to its receptor via multiple routes. We
      also cloned the newest trefoil peptide, intestinal trefoil factor (ITF), from
      human and rat intestinal mucosa. Using in situ hybridization we demonstrated its
      synthesis by normal rat intestinal goblet cells. RNAse protection analysis
      revealed that the level of mRNA for rat ITF in small and large intestine was
      affected by the process of enteral feeding. We conclude that trefoil peptides are
      widely distributed in the intestine in human inflammatory bowel disease and are
      of considerable potential functional importance.

PMID- 8283021
TI  - Role of oxygen radicals in indomethacin-induced gastric mucosal microvascular
      injury in rats.
AB  - To investigate the pathogenesis of indomethacin-induced gastric mucosal injury,
      vascular injury was examined in the rat using Evans blue and monastral blue
      vascular tracers. Extravasation of intravenously injected Evans blue into the
      gastric mucosa was used as an indicator of vascular permeability. Monastral blue
      was used to demonstrate vascular injury morphologically. The extravasated content
      of Evans blue significantly increased and reached the maximum at 2 h after
      indomethacin administration. The increase in Evans blue content was significantly
      inhibited by the pretreatment with superoxide dismutase (SOD) and SOD + catalase,
      but not with catalase alone. Monastral blue-labeled damaged endothelial cells in
      the gastric mucosa also increased at 2 h after indomethacin administration, which
      increase was reduced by pretreatment with SOD and SOD + catalase. These results
      indicate that oxygen radicals, including the superoxide radical, play an
      important role in the microvascular injury induced by indomethacin, which in turn
      plays a primary role in the development of gross hemorrhagic erosions.

PMID- 8283022
TI  - An ethologist aboard HMS Beagle: the young Darwin's observations on animal
      behavior.
AB  - Darwin's notes from the Beagle period abound with observations on animal
      behavior. Although in places anecdotal and anthropomorphic, they include many
      detailed, lively comments of the activities of birds, reptiles, mammals,
      crustacea, insects, and other invertebrates. In his comparative approach, belief
      in the importance of heredity, an understanding that behavior might be of
      assistance in taxonomy, and that it was linked with both the organism's
      morphology and habitat, and his attempts at experiments, Charles Darwin in his
      early and mid-twenties was using techniques and concepts that were to be of great
      significance in his later work.

PMID- 8283023
TI  - Theoretical and methodological foundations of the authoritarian personality.

PMID- 8283024
TI  - Science, government, and the mass production of penicillin.

PMID- 8283025
TI  - John Simon, Robert Lowe, and the origin of state-supported biomedical research in
      nineteenth-century England.

PMID- 8283026
TI  - Amputation in the Civil War: physical and social dimensions.

PMID- 8283027
TI  - TAP (transporter associated with antigen processing)-independent presentation of
      endogenously synthesized peptides is enhanced by endoplasmic reticulum insertion
      sequences located at the amino- but not carboxyl-terminus of the peptide.
AB  - Under most circumstances, cell surface MHC class I molecules display peptides
      derived from a cytosolic pool of proteins. The efficient presentation of such
      peptides requires the functioning of two MHC gene products [TAP1 and TAP2
      (transporter-associated with Ag processing 1 and 2)] that form a complex that
      facilitates transmembrane movement of peptides from the cytosol to the
      endoplasmic reticulum, the site of peptide association with class I molecules. It
      has been previously shown that peptides can be presented in a TAP-independent
      manner in association with HLA A2.1 or H-2 Kd if they are expressed COOH-terminal
      to an endoplasmic reticulum insertion/signal sequence derived from the adenovirus
      E3/19K glycoprotein (Anderson et al., 1991. J. Exp. Med. 174: 489; Eisenlohr et
      al., 1992. Cell 71: 963). We show that: 1) the E3/19K signal sequence greatly
      enhances the presentation of each of four additional peptides tested in
      association with H-2 Kb or Kk, 2) the E3/19K signal sequence can be substituted
      by a signal sequence derived from beta-IFN, and 3) the E3/19K signal sequence
      does not function when located at the COOH terminus of antigenic peptides. These
      findings indicate that first, many peptides require TAP for efficient
      presentation to T cells, second, expression of peptides COOH-terminal to signal
      sequences is a generally applicable method of bypassing the TAP-dependence of
      peptide presentation and third, the leader sequence does not act to bypass TAP
      simply by increasing the hydrophobic nature of peptides.

PMID- 8283028
TI  - T cell activation results in physical modification of the mouse CD8 beta chain.
AB  - The T lymphocyte glycoprotein, CD8, is an essential component of the response of
      class I MHC-restricted T cells to Ag. CD8 is expressed on the surface of class I
      restricted T cells as disulfide-bonded heterodimers and higher multimers of two
      distantly related polypeptides, alpha and beta. The CD8 alpha polypeptide,
      expressed in transfection studies as homodimers, is able to reproduce both the
      adhesive and stimulatory properties of CD8, leaving the function of the CD8 beta
      polypeptide unresolved. Herein we demonstrate that the CD8 beta polypeptide
      changes physically during T cell maturation and activation by reversibly altering
      its sialic acid content. These changes occur specifically on CD8 beta not -alpha,
      indicating that the primary role of the CD8 beta chain may be regulatory,
      influencing the physical structure of the CD8 complex, and suggesting a novel
      mechanism of controlling receptor/ligand interactions.

PMID- 8283029
TI  - Immunity to MHC class I antigen after direct DNA transfer into skeletal muscle.
AB  - Plasmid cDNA encoding the alpha-chain of either membrane-bound (pcRT.45) or
      secreted (pcRQ.B3) RT1Aa MHC class I Ag were transferred to Lewis (RT1(1)) rat
      skeletal muscle by direct injection. Rats were challenged 7 days later with an
      ACI (RT1a) heterotropic heart transplant, and cardiac allograft survival, RT1Aa
      specific antibody levels, and frequency of ACI-specific CTL were monitored. Graft
      rejection was accelerated by > or = 2 days in an Ag-specific and dose-dependent
      manner in pcRT.45-injected rats. The pcRQ.B3-injected rats also rejected grafts
      more rapidly; however, graft rejection was accelerated by only 1 day, and graft
      infiltrates were less pronounced than in pcRT.45-injected rats. Injection of
      pcRT.45 resulted in an increase in ACI-specific CTL precursor frequency 3 days
      post-transplant, whereas there was no significant change in rats pretreated with
      pcRQ.B3 injection. Compared with rats injected with a control plasmid encoding
      firefly luciferase, transfer of pcRT.45 resulted in an increase in RT1Aa-specific
      IgG and IgM antibody 3 days after heart transplantation. Transfer of pcRQ.B3
      resulted in a similar mean increase in RT1Aa-specific IgG and IgM antibody after
      transplantation, but the variability from rat to rat was greater, with some
      animals exhibiting strong priming, and others showing little or no priming by
      gene injection. Our results suggest that skeletal muscle can express either
      membrane-bound or secreted MHC class I Ag after gene transfer, but that the
      membrane-bound form is more immunogenic than the secreted form in the high
      responder Lewis rat. Direct DNA transfer to skeletal muscle provides a rapid and
      specific approach to studying immunity to allogeneic MHC Ag.

PMID- 8283030
TI  - Extrathymic expression of the intracellular hepatitis B core antigen results in T
      cell tolerance in transgenic mice.
AB  - We previously developed a transgenic (Tg) murine lineage (B10.S-Tg31e), which
      secretes the hepatitis B e Ag (HBeAg) into the serum at a concentration of 10
      ng/ml. This serum concentration was sufficient to render B10.S-Tg31e mice
      functionally tolerant at the T cell but not B cell level. To determine the
      tolerogenic potential of an intracellular form of this Ag, namely the hepatitis B
      core Ag (HBcAg), expressed outside the thymus, the B10.S-Tg10c lineage was
      developed. In B10.S-Tg10c mice the HBcAg is expressed as an intracellular "self"
      Ag predominantly in the liver, and cannot be detected in the serum, the thymus or
      in nonthymic lymphoid tissue. Despite the liver-specific and intracellular
      location of this transgenic self-protein, B10-STg10c mice demonstrate a
      significant degree of HBcAg-specific T cell tolerance at the level of T cell
      proliferation. Similarly, in vivo anti-HBc antibody production after HBcAg
      immunization is significantly reduced as compared with non-Tg littermate
      controls. No spontaneous anti-HBc antibody is produced in B10.S-Tg10c mice,
      however, adoptive transfer of HBcAg-specific T cells from non-Tg B10.S mice
      elicits anti-HBc specific "autoantibody" production. Interestingly, antibodies
      with specificity for the HBeAg as well as the HBcAg are produced. Antibody
      production in B10.S-Tg10c mice adoptively transferred with T cells indicates that
      sufficient native HBcAg can gain access to the extracellular compartment to
      engage HBcAg-specific B cells that are clearly not tolerant in this model. No
      liver injury was observed as a consequence of HBcAg expression, even in B10.S
      Tg10c mice adoptively transferred with HBcAg-specific T cells. Unless HBcAg is
      unique in this regard, these results suggest that organ-specific, intracellular
      self-Ag may be released during normal cell turnover in sufficient concentrations
      to elicit systemic T cell tolerance. B10.S-Tg10c mice also serve as an
      immunologic model system for chronic infection with the HBeAg-negative mutant of
      the hepatitis B virus.

PMID- 8283031
TI  - Mechanism of virus-induced Ig subclass shifts.
AB  - Infection of mice with live viruses leads to a dramatic increase in the amount of
      IgG2a Ig with a consequent shift in the ratio of IgG1/IgG2a. To examine the Ig
      subclass shift induced by viral infection, we challenged mice with live virus,
      inactivated virus, or replication-defective mutant viruses that were able to
      infect cells and produce some viral proteins but were not able to complete a
      replicative cycle. While killed (or inactivated) virus was capable of inducing
      HSV-specific antibody, it did not stimulate a shift in the subclass of the total
      Ig. Replication-defective mutant viruses that fail to express a functional ICP8
      or ICP27 protein, but not a mutant expressing a defective ICP4 protein, were able
      to stimulate the shift. Thus, only a portion of the lytic cycle is sufficient to
      induce the shift. At least part of the effect is mediated by IFN-gamma.

PMID- 8283032
TI  - Increased proliferation, cytotoxicity, and gene expression after stimulation of
      human peripheral blood T lymphocytes through a surface ganglioside (GD3)
AB  - Previous studies have suggested that gangliosides have an important role in cell
      signaling and recognition. However, their specific function in these processes
      has not been clearly defined. A mAb, R24, that reacts specifically with a cell
      surface ganglioside (GD3) has been demonstrated to stimulate proliferation of T
      cells derived from human peripheral blood. In this study, we have investigated
      the mechanisms by which the R24 mAb affects T cell functions. We have observed
      that the R24 mAb stimulates GD3+ T cell proliferation, cytotoxicity, and surface
      marker expression of IL-2R alpha-chain, IL-2R beta-chain, HLA-DR, CD11a, and
      CD11c. Additionally, IFN-gamma activity but not IL-1, IL-2, or IL-4 activity was
      present in culture supernatants 72 h after R24 stimulation. In some donors,
      increased IL-6 and TNF-alpha activity also was detected after R24 treatment.
      Furthermore, R24 treatment resulted in translocation of c-rel, but little or no
      NF kappa B p50 or p65, from the cytoplasm to the nucleus and an increase of NF
      kappa B binding complexes containing c-rel and p50. This treatment also caused
      increased tyrosine phosphorylation of specific protein substrates. R24-stimulated
      increases in proliferation, cytotoxicity, and cell surface protein expression
      could be blocked by cyclosporin and staurosporin, indicating that
      cyclophilin/calcineurin and protein kinase C may be involved in the R24 signaling
      pathway. Additionally, herbimycin A, a tyrosine kinase inhibitor, blocked the R24
      stimulated increase in proliferation but not cytotoxicity at concentrations
      consistent with specificity for tyrosine kinases. These results suggest that
      multiple biochemical pathways are involved in the activation of human T cells by
      R24.

PMID- 8283033
TI  - Environmental signals influencing expression of the IFN-gamma receptor on human T
      cells control whether IFN-gamma promotes proliferation or apoptosis.
AB  - IFN-gamma R expression is subject to contrasting modulation on human T cells. IFN
      gamma R constitutive expression is low on three human malignant T cells (ST4,
      PF382, and Jurkat) growing in medium supplemented with serum. The addition of IFN
      gamma down-modulates IFN-gamma R expression and increases both proliferation and
      MHC class I Ag expression. By contrast, when malignant T cells are cultured in
      medium without serum, IFN-gamma R expression dramatically increases and the cells
      undergo a slow apoptotic death. The addition of IFN-gamma enhances apoptosis and
      inhibits cell rescue in serum-supplemented medium. This opposite ability of IFN
      gamma to stimulate malignant T cell proliferation or death correlates with the
      intensity of IFN-gamma R cell expression, high expression being a marker for cell
      apoptosis. IFN-gamma R up-modulation also occurs on malignant T cells undergoing
      apoptosis after treatment with dexamethasone, on irradiated normal CD3+ PBL, and
      on cultured normal CD3+ thymocytes. Moreover, the ability of IFN-gamma to augment
      apoptosis of highly IFN-gamma R-positive thymocytes suggests that its role in
      promoting T cell apoptosis is also important in physiologic conditions.

PMID- 8283034
TI  - Urokinase receptor. An activation antigen in human T lymphocytes.
AB  - The ability of activated T lymphocytes to extravasate and reach inflammatory and
      malignant foci in the tissues is a basic function of cellular immunity. Recent
      evidence strongly suggests that the urokinase receptor (uPAR) holds a central
      position in the development of human two-chain urokinase-mediated pericellular
      proteolysis and matrix degradation, an important element in cell migration. In
      this report we establish uPAR as a pan T cell activation Ag. As determined by
      FACS analysis, CD3+ lymphocytes from healthy donors exhibited no significant uPAR
      expression. In contrast, patients (e.g., HIV-positive donors) showed distinct
      uPAR expression, confined to HLA-DR+ cells, in up to 80% of all T cells. In vitro
      activation by PMA caused a rapid up-regulation of membrane uPAR in all healthy
      donor T cells and was accompanied by enhanced receptor synthesis and elevated
      uPAR mRNA levels. A similar induction resulted from activation via the TCR/CD3
      complex using mitogens (PHA, and Con A), anti-CD3 antibodies, and alloantigen.
      Receptor expression at single cell level was also modulated by a number of
      cytokines. IL-2, IL-4 and IL-7 increased uPAR presentation on 20 to 50% of the T
      cell population, and combined stimulation of bulk cultures demonstrated an
      additive effect of IL-2 and IL-7, whereas the response to each of the two was
      inhibited by IL-4. In addition, TGF-beta 1 substantially reduced the uPAR
      expression in T cell cultures responding to PHA, IL-2, and IL-7. Irrespective of
      the activating reagent, the T cells appeared to produce the same molecular uPAR
      species, but the affinity of uPAR expressed in PMA blasts was decreased,
      presumably because of a differential location at the cell surface. All activated
      cultures showed co-expression of uPAR and CD25. The finding that the urokinase
      receptor is an activation Ag may suggest that cell-associated plasminogen
      activation is involved in extravasation and migration of activated T cells.

PMID- 8283035
TI  - Conditional ablation of dendritic cells in transgenic mice.
AB  - Dendritic cells (DC) are professional Ag-presenting cells that play a major role
      in T cell-mediated immune responses and in thymocyte differentiation. To better
      analyze their physiological importance, we sought to generate transgenic mice
      presenting a conditional DC deficiency. We used a strategy based on the cell
      specific expression of a suicide gene. The DC-targeted expression is obtained
      using HIV regulatory sequences; indirect evidence has suggested that these
      sequences control a preferential expression in DC. The suicide gene is the herpes
      simplex virus type 1 thymidine kinase (HSV1-TK) which allows conditional ablation
      of dividing HSV1-TK-expressing cells by converting nucleoside analogs such as
      ganciclovir (GCV) into toxic molecules. We generated transgenic mice expressing
      an HSV1-TK gene transcribed from HIV regulatory sequences. A low but significant
      HSV1-TK expression was observed in mature DC and DC precursors grown from
      granulocyte-macrophage colony-stimulating factor-supplemented bone marrow
      cultures. These HSV1-TK-expressing DC precursors are specifically killed by GCV.
      We next treated transgenic mice with GCV, and obtained a specific ablation of DC
      in spleen and thymus. Ninety percent of spleen DC could be depleted within a
      week, indicating a turnover rate of approximately 15% per day. Interestingly,
      this DC depletion always correlated with a major thymic atrophy and disappearance
      of CD4+CD8+ thymocytes. This animal model should help to assess the physiological
      role of DC in the immune response and in thymocyte differentiation. It should
      also help to appreciate the consequences of DC dysfunction in pathological
      situations, such as HIV-infection or allograft rejection.

PMID- 8283036
TI  - Helper-cytotoxic T lymphocyte (CTL) determinant linkage required for priming of
      anti-HIV CD8+ CTL in vivo with peptide vaccine constructs.
AB  - CTL are a critical component of protective immunity against viral infections, but
      requirements for in vivo priming of CTL are not completely understood. Covalent
      linkage of a helper determinant to a CTL determinant, analogous to that required
      for cognate help for antibody production, does not appear to be necessary in
      vitro, but its necessity has not been extensively explored in vivo, especially at
      a molecular level. We previously defined peptides encompassing multideterminant
      regions of HIV-1 gp160 (cluster peptides) recognized by Th from mice and humans
      of multiple MHC types. To investigate the requirement for Th in the development
      of CTL in vivo, in the context of developing a synthetic peptide vaccine for HIV
      active in multiple strains of mice, we immunized with compound peptides
      representing an immunodominant CTL epitope, P18, of gp160, co-linearly
      synthesized at the C-terminus of three cluster peptides. Spleen cells from
      compound-peptide-immunized mice of three MHC haplotypes sharing the Dd class I
      MHC molecule but with different class II molecules exhibited enhanced gp160
      specific CD8+ CTL activity and CD4+ Th. In contrast, immunization with P18 alone
      or a mixture of cluster peptide and P18 elicited only marginal CTL activity.
      These results imply a requirement for determinant linkage in CTL induction in
      vivo similar to that already well recognized for cognate help for antibody
      induction. The results also define promising peptide HIV vaccine candidates for
      induction of CTL, as well as neutralizing antibodies, in diverse MHC types.

PMID- 8283037
TI  - Expression of Bruton's agammaglobulinemia tyrosine kinase gene, BTK, is
      selectively down-regulated in T lymphocytes and plasma cells.
AB  - The gene mutated in the human disease, X-linked agammaglobulinemia (XLA), is
      related to the Src gene family of cytoplasmic protein-tyrosine kinases and is
      designated Btk (Bruton's agammaglobulinemia tyrosine kinase; formerly Atk/Bpk;
      the human gene is denoted BTK, using capital letters according to the kinase
      nomenclature). We have recently reported that this gene is expressed in B
      lymphocytes and that the specific mRNA was undetectable in T cells using Northern
      blotting. Further analyses of different sources of B and T lymphocytes confirmed
      this pattern. However, BTK transcripts were undetectable in four plasmacytoma
      lines. Moreover, as virtually normal amounts of BTK transcripts were found in
      PBMC from two patients carrying a point mutation in BTK, despite low B cell
      numbers, we anticipated that the gene would also be expressed in cells of other
      lineages. The erythroleukemia cell line K-562, the promyelocytic line HL-60 and
      the histiocytic lymphoma line U-937 were found to have BTK mRNA levels comparable
      to B cells. BTK mRNA was also detected in monocytes from healthy donors as well
      as in the human immature basophilic cell line KU812, in the human mast cell
      leukemia cell line HMC-1 and in the CD34 expressing myeloblast KG-1. A similar
      expression pattern was obtained when BTK protein was analyzed by
      immunoprecipitation and Western blotting. Using a polymerase chain reaction-based
      analysis, a small amount (less than 1% of the level in B cells) of BTK mRNA was
      identified in T lymphocytes. Our findings are compatible with a general
      expression of the BTK gene in hematopoietic cells, except in T lymphocytes and
      plasma cells, in which the transcript level is selectively down-regulated.

PMID- 8283038
TI  - Autocrine stimulation of B lymphocytes by a platelet-activating factor receptor
      agonist, 1-palmitoyl-2-acetyl-sn-glycero-3-phosphocholine.
AB  - Based on previous data which demonstrated the ability of platelet-activating
      factor (PAF) antagonists to inhibit constitutive immunoglobulin synthesis in B
      lymphoblastoid cell lines, we determined the capacity of these cells to
      synthesize PAF or 1-palmitoyl-2-acetyl-sn-glycero-phosphocholine (PAGPC), an acyl
      PAF identified in various cell types. In two B-lymphoblastoid cell lines (LA350
      and HSCE-), significant amounts of production of PAGPC were detected, whereas the
      amount of PAF was below the level of detection in our system. The biologic
      effects of PAGPC were examined in these cells, both of which have well
      characterized PAF receptors. PAGPC induced a concentration-dependent increase in
      intracellular Ca2+ concentrations and activation of MAP-2 kinase (as detected by
      immunoblotting and measurements of kinase activity) in these cells. The kinetics
      and magnitude of these responses were similar to those induced by PAF, and they
      were inhibited by Web 2086, a PAFR antagonist. Phosphatidylcholine, which differs
      from PAGPC in that it contains a long fatty acid residue at position 2, did not
      induce any of these responses. A mutual cross-desensitization of the B
      lymphoblasts between PAGPC and PAF was observed for Ca2+ mobilization. To induce
      maximal cell stimulation, approximately 600-fold higher concentrations of PAGPC
      than of PAF were needed. Because the two B-lymphoblastoid cell lines synthesized
      significant amounts of PAGPC, this phospholipid may participate in an autocrine
      stimulation pathway in B cells. Furthermore, the data indicate that PAGPC is an
      agonist for the PAFR in B lymphoblasts and that the ether linkage in the PAF
      molecule is not an absolute requirement for activity, although it increases the
      potency of the ligand.

PMID- 8283039
TI  - Functional analysis of human Fc gamma RII (CD32) isoforms expressed in B
      lymphocytes.
AB  - The low affinity IgG receptor Fc gamma RII (CD32) represents the most widely
      distributed class of human Fc gamma R. To analyze the biologic functions of
      different Fc gamma RII isoforms, we stably transfected Fc gamma RIIb1, IIb1*,
      IIb2, IIa, and a IIa tail- mutant to the mouse IIA1.6 B lymphoma cell line. Of
      these, Fc gamma RIIb1* represents a receptor variant that is identical to IIb1
      except for a single amino acid difference in the cytoplasmic tail (amino acid
      position 11) where a tyrosine (IIb1) is replaced by an aspartic acid (IIb1*).
      Evaluation of capping ability showed the Fc gamma RIIb1 molecules to cap
      effectively, which was even more apparent with IIb1*. None of the Fc gamma RIIa,
      IIa tail-, or IIb2 isoforms capped significantly. Internalization of Fc gamma R
      antibody complexes proved very efficient for both the Fc gamma RIIa and IIb2
      isoforms, whereas the IIb1 molecules internalized moderately compared with IIb1*,
      which internalized less efficiently. Notably, human IgG aggregates were
      internalized effectively by Fc gamma RIIa and moderately by IIb2. Neither Fc
      gamma RIIb1 nor IIb1* proved capable of internalizing such IgG aggregates. Cross
      linking of the different Fc gamma R molecules showed Fc gamma RIIa capable of
      triggering increases in [Ca2+]i. Fc gamma R expressed on B cells were able to
      down-regulate [Ca2+]i on co-cross-linking with slgG. Notably, all three Fc gamma
      RIIb receptors proved active in this respect, in contrast to Fc gamma RIIa. The
      cell distribution of these Fc gamma RII isoforms was analyzed in a panel of human
      B cell lines to complement the IIA1.6 B cell model. Fc gamma RIIa was found
      expressed both at message and protein levels in all tested human B cell lines. In
      the pre-B cell lines evaluated, no Fc gamma RIIb molecules were detectable,
      whereas both Fc gamma RIIb1 and IIb2 molecules were found present in more mature
      B cell lines. These data support both a complex expression pattern of Fc gamma
      RII isoforms in B cell lines and functional differences between these B cell
      molecules.

PMID- 8283040
TI  - Expansion/deletion of mature T cells exposed to endogenous superantigens in vivo.
AB  - Previous studies have shown that in thymectomized hosts exposure of mature T
      cells to Mlsa (mtv-7) Ag in vivo leads to specific tolerance and the
      disappearance of Mlsa-reactive V beta 6+ T cells after an initial phase of T cell
      expansion. To investigate the factors controlling postthymic elimination of
      mature T cells, we examined T cell responses to Mlsa and other endogenous
      superantigens in a number of different strain combinations. The results show that
      the extent of T cell expansion/deletion is influenced by various factors,
      including the H-2 haplotype of the host and the particular V beta studied.
      Collectively, the results suggest that the extent of elimination of mature T
      cells is variable and may be a function of high avidity interactions with APC.

PMID- 8283041
TI  - Kinetics and specificity of peptide-MHC class II complex displacement reactions.
AB  - The peptide-induced acceleration of the dissociation of pre-formed complexes of
      the detergent-solubilized mouse class II molecules IEd and IEk with fluorescein
      labeled peptides was investigated using high-performance size exclusion
      chromatography. While it is generally believed that functional complexes of MHC
      class II alpha beta heterodimers and peptides have a 1:1 stoichiometry, the data
      provide qualitative as well as quantitative kinetic evidence that the enhancement
      of the release of one peptide by a second peptide is due to a two-peptide
      intermediate. Different combinations of peptides were tested for their ability to
      accelerate each other's release from IEd. The importance of positive charge for
      the interaction with IEd was confirmed by the finding that not only dynorphin 1
      13 but also poly-L-lysine (14-19 mer) and a peptide corresponding to a
      mitochondrial presequence (net charge +6) efficiently enhance the release of pre
      bound peptides. SDS-PAGE analysis revealed that the efficiently displacing
      peptides do not stabilize the IEd alpha beta heterodimer at acidic pH, in
      contrast to the IEd-restricted antigenic peptide HEL 107-116. The data support a
      mechanism in which the second peptide binds specifically to the pre-formed class
      II-peptide complex, which, depending on the properties of the peptides involved,
      leads to the destabilization of the complex and the release of the first peptide.

PMID- 8283042
TI  - Neonatal VH, D, and JH gene usage in rabbit B lineage cells.
AB  - The neonatal antibody repertoire in both mouse and humans differs from that of
      the adult repertoire in that the neonatal repertoire uses a limited set of JH
      proximal VH genes but the adult repertoires use many different VH genes. Rabbits
      are unusual in that adults use only three or four VH genes, with approximately
      80% of the B cells using VH1, the 3'-most VH gene. To investigate whether the
      repertoire of neonatal rabbits differs from that of adults, we analyzed VH, D,
      and JH gene usage in B cells of neonatal rabbits. A total of 68 rearranged VDJ
      genes was cloned from mRNA and genomic DNA isolated from lymphoid tissues of
      newborn to 10-day-old rabbits. We found that 74% of the VDJ gene rearrangements
      utilized VH1 and 15% utilized the genes that we designated VHx or VHy. From the
      remaining VDJ genes we identified seven novel VH genes, one, VHz, which was found
      in mRNA. We conclude that the repertoire of utilized VH genes in neonates is
      limited and is similar to that of adult rabbits. We also found the D1, D2a, D2b,
      and JH4 gene segments preferentially rearranged. We suggest that the preferential
      usage of VH, D, and JH gene segments in VDJ genes is caused by preferential
      rearrangement rather than by selective expansion of B cells that utilize the gene
      segments.

PMID- 8283043
TI  - Structural analysis of the human VH locus using nonrepetitive intergenic probes
      and repetitive sequence probes. Evidence for recent reshuffling.
AB  - The organization and evolution of the 0.8-Mb JH-proximal region in the human Ig
      VH locus were studied by mapping DNA fragments hybridized to non-repetitive
      intergenic probes and by determination of the content and distribution of
      repetitive sequences. Southern blot analysis of cloned DNA covering the 0.8-Mb
      region with intergenic probes allowed us to map two to seven cross-hybridizing
      fragments by each probe. Clusters of fragments detected by an identical set of
      probes appeared repeatedly within the 0.8-Mb JH-proximal region. Distantly
      located VH segments flanked by a cluster of DNA fragments hybridized by the same
      set of probes were highly homologous to each other, providing evidence for recent
      frequent duplication and translocation throughout the locus. DNA fragments
      detected by the same set of probes were orientated with the same 5' to 3' order
      within the cluster, suggesting little involvement of inversion upon recombination
      in the locus. The content of interspersed Alu and L1 sequences in the VH locus
      were not significantly greater than the average in the genome.

PMID- 8283044
TI  - Molecular analysis of mercury-induced antinucleolar antibodies in H-2S mice.
AB  - In H-2S mice, the administration of mercuric chloride results in the development
      of antinucleolar autoantibodies. These mice represent a valuable model to study
      the role of environmental factors in the development of systemic autoimmunity. We
      have obtained seven antinucleolar mAb from mercury-injected A.SW mice and
      characterized their specificities and V genes. All mAb immunoprecipitate the U3
      and U8 ribonucleoprotein particles (RNP) and some (but not all) react with
      fibrillarin, the only currently characterized protein component of mammalian
      nucleolar RNP. Several VH and V kappa genes are recurrently used by these
      antinucleolar RNP mAb and their H chain CDR3 segments contain several acidic
      residues that may be important for binding to the cationic proteins composing the
      nucleolar RNP. Our results support the concept that in H-2S mice administration
      of mercury induces a specific loss of tolerance to nucleolar RNP.

PMID- 8283045
TI  - Production of mouse V/human C chimeric kappa genes by homologous recombination in
      hybridoma cells. Analysis of vector design and recombinant gene expression.
AB  - Homologous recombination between transferred and chromosomal Ig genes in mouse
      hybridoma cells offers a general method of altering the chromosomal Ig genes in
      predetermined ways. Recombination is infrequent in hybridoma cells, and we have
      been interested in improving the methods for identifying and recovering the rare
      recombinants. We have used vectors that are designed to replace the mouse
      chromosomal C kappa segment with the human equivalent, so that recombinants
      produce mouse V/human C chimeric kappa-chains. We describe an enhancerless,
      replacement type vector that can be used with the herpes thymidine kinase
      counterselection to provide such enrichment that homologous recombinants
      constitute 15% of the selected G418-resistant, FIAU-resistant cells. We have also
      measured the level of chimeric kappa gene expression and found surprisingly that
      (1) it is very variable among transformants with the same recombinant gene
      structure, (2) there is no systematic difference in the level of production by
      recombinants that retain or have lost the J-C kappa intron enhancer, and (3) the
      amount of chimeric kappa mRNA in even the highest producing transformants is much
      less than the amount of the corresponding mouse kappa mRNA.

PMID- 8283046
TI  - Cerebral expression of multiple cytokine genes in mice with lymphocytic
      choriomeningitis.
AB  - The simultaneous expression of multiple cytokine genes was examined within the
      brain and peripheral organs of euthymic and congenic athymic mice during the
      course of lymphocytic choriomeningitis (LCM) induced by the intracranial
      inoculation of LCM virus. In euthymic mice, levels of TNF-alpha, IL-1 alpha, IL
      6, and IL-1 beta mRNA in the brain increased early in infection and further
      increased with the progression of disease; the level of IFN-gamma mRNA was
      expressed at high levels late in infection and correlated with the onset of
      clinical disease. In the peripheral organs, TNF-alpha, IL-1 alpha, and IL-1 beta
      gene expression predominated early and then declined late in disease. In athymic
      mice (which do not develop LCM), expression of TNF-alpha, IL-1 alpha, IL-6, and
      IL-1 beta mRNA increased progressively in brain and peripheral organs from days 3
      to 6 postinfection. The levels of these transcripts were significantly lower than
      those in infected euthymic animals. In euthymic mice, in situ hybridization
      revealed IFN-gamma-, TNF-alpha-, and IL-1 alpha-expressing cells throughout the
      inflammatory cell infiltrates associated with areas of LCMV nucleic acid.
      Therefore, in mice with LCM there is simultaneous expression of multiple cytokine
      genes, the pattern of which is distinct for brain vs peripheral organs and for
      euthymic vs athymic mice. The close spatiotemporal relationship between
      expression of cytokine genes and evolution of disease in brain implicate
      cytokines are not only key coordinators of the host response but also as possible
      mediators of neuropathology in LCM.

PMID- 8283047
TI  - Effect of granulocyte-macrophage colony-stimulating factor on rat alveolar
      macrophage anticryptococcal activity in vitro.
AB  - Cryptococcus neoformans, a pathogenic fungus usually acquired by inhalation,
      causes the most common lethal mycosis in AIDS. The resident lung phagocytes,
      alveolar macrophages (AM phi), inhibit growth of C. neoformans poorly unless
      activated by cytokines such as IFN-gamma. In this study, we examined the effect
      of rat AM phi of the potent hematopoietic and M phi-activating cytokine,
      granulocyte-macrophage CSF (GM-CSF), alone and in combination with other
      cytokines. Rat AM phi monolayers were preincubated with 0.1 to 1000 U/ml GM-CSF
      without or with other recombinant cytokines, and then were incubated with viable
      C. neoformans (strain H99/C3D). Growth inhibition was assessed by counting
      cryptococcal CFU at 24 and 48 h of coculture; AM phi proliferation was assessed
      by measuring both uptake of [3H]TdR and AM phi numbers. AM phi preincubated with
      GM-CSF for 5 days (but not for shorter periods) inhibited growth of C.
      neoformans. Anticryptococcal activity required direct contact of AM phi with C.
      neoformans, but once induced by preincubation, did not require continued exposure
      to GM-CSF. Induction of anticryptococcal activity by GM-CSF was dose dependent
      (maximal induction at 250 U/ml), and was due to both increased ingestion and
      killing. GM-CSF induced AM phi proliferation, but anticryptococcal activity was
      not due totally to increases in AM phi numbers, indicating AM phi activation by
      GM-CSF. GM-CSF-induced AM phi proliferation was increased by IL-6, unchanged by
      IL-8, and abolished by LPS or IFN-gamma. However, IL-6 did not increase GM-CSF
      induced anticryptococal activity. The combination of GM-CSF and IFN-gamma showed
      rapid and sustained anticryptococcal activity, unlike either cytokine alone. Our
      in vitro data suggest that the combination of GM-CSF and IFN-gamma may have
      beneficial effects on host defense against C. neoformans in vivo.

PMID- 8283048
TI  - Protective immunity linked with a distinct developmental stage of a filarial
      parasite.
AB  - Repeated low dose infections of the jird Meriones unguiculatus, with the filarial
      parasite Acanthocheilonema viteae cause a substantial reduction of the total worm
      burden, suggesting a parasite-driven immune mechanism that controls super
      infections. Quantitative recovery of parasites from tissues of triple infected
      jirds reveals that the larvae derived from a subsequent challenge infection are
      inactivated or severely impaired several days after transmission, precisely
      during their molt from the L3 to the L4 stage. Moreover, only larvae undergoing
      the molt from L3 to L4 stages are capable of stimulating an immune response
      directed against the challenge infection, indicating that protective Ag are
      produced during the molting period. Consistent with this, inactivated L3 or live
      L4 do not produce the same effect. In contrast to susceptible animals, immune
      jirds elicit high serum antibody titers against molting Ag. Indirect fluorescence
      antibody-binding tests with sera from protected jirds reveal specific labeling of
      the surface of molting L3 and not other larval stages, implying a stage-specific
      elimination process. The identification of molting L3 as a natural target for
      host immune mechanisms, emphasizes the central importance of this larval stage
      for future efforts aimed toward the development of a filarial vaccine.

PMID- 8283049
TI  - Complement receptor-mediated uptake and tumor necrosis factor-alpha-mediated
      growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages.
AB  - The relative phagocytosis and intracellular fate of Mycobacterium tuberculosis
      (MTB) (H37Ra) in human alveolar macrophages (AM) and their precursors blood
      monocytes (MN) was investigated. Uptake of MTB by MN and AM was confirmed by
      electron microscopy. At an infection ratio of 100:1 (MTB:target cell), the
      percentage of infected AM and the number of MTB per AM was > MN (p < 0.001, p <
      0.0001, respectively). Uptake of MTB was increased by increasing concentrations
      of serum and decreased in the presence of heat-inactivated serum. Among
      complement receptors (CR) CR1, CR3, and CR4, the major CR mediating uptake of MTB
      by MN were CR1 and CR3, whereas for AM, CR4 was the major CR. When MN and AM were
      infected with MTB and cultured for up to 7 days, AM limited intracellular growth
      of MTB more effectively than MN as determined by a CFU assay. MTB stimulated
      production of TNF-alpha by mononuclear phagocytes and by AM > MN (p < 0.007).
      Pentoxifylline inhibited TNF-alpha production by mononuclear phagocytes and
      concurrently increased MTB growth (AM > MN). A polyclonal neutralizing antibody
      to TNF-alpha also increased MTB growth in AM. Thus, AM are more efficient in
      phagocytosis of MTB than MN, and uptake is mediated through CR4 to a greater
      extent than CR1 or CR3. The slowed replication of MTB in AM is associated with an
      increase in TNF-alpha production, and intracellular growth is promoted by
      pentoxifylline and neutralizing antibody to TNF-alpha. These data suggest that AM
      may play a prominent and efficient role in the primary defense of the lung in
      tuberculosis through CR-mediated uptake, predominantly CR4, and TNF-alpha
      mediated killing of MTB.

PMID- 8283050
TI  - Transforming growth factor-beta 1 inhibits inflammatory cytokine-induced C3 gene
      expression in astrocytes.
AB  - In this report, we show that transforming growth factor-beta (TGF-beta) can
      significantly inhibit the capacity of IFN-gamma, IL-1 beta, and TNF-alpha to
      augment expression of the central component of complement C3 in the human
      astroglioma cell line D54-MG. Treatment of D54-MG cells with TGF-beta alone had
      no dose- or time-dependent effect on basal C3 protein or mRNA levels. However,
      TGF-beta suppressed induction of C3 expression at both the protein and mRNA level
      in D54-MG cells treated with inflammatory cytokines. The extent of TGF-beta
      mediated suppression was cytokine-specific, and suppression of protein production
      did not necessarily correspond to reductions in steady-state mRNA levels for each
      cytokine. Similar findings were obtained at the mRNA level using primary rat
      astrocytes, indicating that TGF-beta can modulate C3 gene expression in
      nontransformed astrocytic cells. Kinetic studies demonstrated that TGF-beta
      mediates its suppressive effect for at least 72 h, and that pretreatment of cells
      with TGF-beta for as little as 2 h significantly reduced the ability of all three
      inflammatory cytokines to enhance C3 expression. Our results suggest that TGF
      beta may play an important role in modulating the endogenous synthesis of
      complement by astrocytes under inflammatory conditions.

PMID- 8283051
TI  - Tyrosine-containing activation motif-dependent phagocytosis in mast cells.
AB  - FcR capable of triggering cell activation share with BCR and TCR a conserved
      intracytoplasmic tyrosine-containing activation motif (TAM). Besides cell
      activation, these receptors trigger other biologic responses, such as endocytosis
      of soluble ligands. Murine mast cells express two types of FcR that, when
      aggregated by antibodies and multivalent Ag, trigger the release of inflammatory
      mediators and cytokines. These are high affinity receptors for IgE (Fc epsilon
      RI) and low affinity receptors for IgG (Fc gamma RIII). They comprise each an IgE
      or IgG-binding alpha-subunit and two TAM-containing subunits that associate with
      both receptors: a beta-subunit and a homodimeric gamma-subunit that can associate
      also with the other subunits of the TCR. Herein, we focused on biologic
      activities triggered in mast cells via the TAM of the gamma-subunits. Using rat
      basophilic leukemia (RBL) cells stably transfected with cDNA-encoding murine Fc
      gamma RIII alpha, we found that murine Fc gamma RIII trigger the phagocytosis of
      antibody-coated erythrocytes. Using RBL transfectants expressing Fc gamma RIII
      with a deletion of the intracytoplasmic domain of Fc gamma RIII alpha or chimeric
      receptors having the extracellular and transmembrane domains of Fc gamma RII and
      the intracytoplasmic domain of Fc gamma RIII alpha, we showed that
      intracytoplasmic sequences of Fc gamma RIII alpha are neither necessary nor
      sufficient for Fc gamma RIII to trigger phagocytosis. Using RBL transfectants
      expressing chimeric receptors having the extracellular and transmembrane domains
      of Fc gamma RII and the TAM-containing intracytoplasmic domain of murine Fc gamma
      RIII gamma, we demonstrated that intracytoplasmic sequences of Fc gamma RIII
      gamma are sufficient to trigger phagocytosis. Using RBL transfectants expressing
      the same Fc gamma RII-III gamma chimeras, in the TAM of which one, the other, or
      both tyrosine residues were mutated, we established that tyrosines in the TAM
      sequence are required for phagocytosis. Our results endow TAM gamma with
      previously unknown triggering capacities and Fc gamma RIII with new biologic
      properties.

PMID- 8283052
TI  - Receptor-dependent internalization of platelet-activating factor.
AB  - A human neutrophil platelet-activating factor (PAF) receptor expressed in
      transfected cells was utilized to study receptor-dependent interactions with the
      ligand. This receptor displays ligand-binding properties comparable with those
      observed with naturally occurring receptor-positive cells when binding
      experiments are performed using COS-7 cells at 4 degrees C. The ligand-receptor
      interaction is markedly temperature dependent, with approximately 10-fold more
      [3H]PAF specifically associated with the cells at 37 degrees C than at 4 degrees
      C. Such temperature dependence is not observed with other ligand-receptor pairs.
      At 37 degrees C essentially all the cell-associated PAF appears to be
      internalized and incorporated into a phospholipid pool. In the absence of
      transfected receptor no specific binding is detected in COS-7 cells at 4 degrees
      C, and at 37 degrees C, no significant ligand internalization is observed. The
      epitope-tagged fusion protein, Flag-PAF receptor, was used to track the receptor
      independently of ligand binding, and showed that the receptor protein expressed
      on the cell surface is not influenced by temperature alone. Incubation with PAF
      at 37 degrees C resulted in the disappearance of approximately 20% of the Flag
      PAF receptor epitope from the cell surface relative to cells incubated without
      PAF or cells preincubated with or without PAF at 4 degrees C. Ligand
      internalization in PAF receptor-transfected cells is inhibited by the receptor
      antagonist, WEB 2086, further supporting the receptor-dependence of this action.
      Stimulation of untransfected cells with phorbol ester, or C5a receptor
      transfected cells with C5a, shows minimal increase in PAF internalization
      relative to PAF receptor-transfected cells, another feature that distinguishes
      the receptor-dependent pathway. These data suggest that in the COS-7 cell system
      PAF internalization is dependent on expression of the PAF receptor, and that the
      apparently nonspecific uptake observed in human neutrophils and other cells may
      involve receptor-independent mechanisms.

PMID- 8283053
TI  - Regulatory interaction of N-formyl peptide chemoattractant receptors with the
      membrane skeleton in human neutrophils.
AB  - The cytoskeleton and/or membrane skeleton has been implicated in the regulation
      of N-formyl peptide receptors. The coupling of these chemotactic receptors to the
      membrane skeleton was investigated in plasma membranes from unstimulated and
      desensitized human neutrophils using the photoreactive agonist N-formyl-met-leu
      phe-lys-N epsilon-[125I]2(p-azidosalicylamido)ethyl-1,3'- dithiopropionate (fMLFK
      [125I]ASD). When membranes of unstimulated cells were solubilized in Triton-X
      100, a detergent that does not disrupt actin filaments, only 50% of the
      photoaffinity-labeled receptors were solubilized sedimenting in sucrose density
      gradients at a rate consistent with previous reports. The remainder were found in
      the pellet fraction along with the membrane skeletal actin. Solubilization of the
      membranes in the presence of p-chloromercuriphenylsulfonic acid, elevated
      concentrations of KCl, or deoxyribonuclease I released receptors in parallel with
      actin. When membranes from neutrophils, desensitized by incubation with fMLFK
      [125I]ASD at 15 degrees C, were solubilized, nearly all receptors were recovered
      in the pellet fraction. Incubation of cells with the ligand at 4 degrees C
      inhibited desensitization partially and prevented the conversion of a significant
      fraction of receptors to the form associated with the membrane skeletal pellet.
      In these separations the photoaffinity-labeled receptors not sedimenting to the
      pellet cosedimented with actin. Approximately 25% of these receptors could be
      immunosedimented with antiactin antibodies suggesting that N-formyl peptide
      receptors may interact directly with actin. These results are consistent with a
      regulatory role for the interaction of chemotactic N-formyl peptide receptors
      with actin of the membrane skeleton.

PMID- 8283054
TI  - Fc gamma R-mediated endocytosis and expression of cell surface Fc gamma RIIb1 and
      Fc gamma RIIb2 by mouse bone marrow culture-derived progenitor mast cells.
AB  - Mouse IL-3-dependent, bone marrow culture-derived mast cells (BMMC) bind IgG
      immune complexes through Fc receptors for IgG (Fc gamma R) but express minimal Fc
      gamma RIII on their surfaces. BMMC do not degranulate appreciably when their Fc
      gamma R are perturbed with the rat anti-mouse Fc gamma RII/III mAb 2.4G2 and
      F(ab')2 mouse anti-rat IgG (MAR). In contrast, after their Fc gamma R were cross
      linked with mAb 2.4G2 and Na125I-labeled MAR at 37 degrees C, BMMC rapidly
      internalized the complex. To identify the Fc gamma R species expressed on the
      surface of BMMC and therefore implicated in the endocytic response, two rabbit
      antipeptide antisera were raised, one against a sequence common to the
      cytoplasmic regions of Fc gamma RIIb1 and Fc gamma RIIb2 and the other to a
      unique cytoplasmic region of Fc gamma RIIb1. When Fc gamma R were
      immunoprecipitated with mAb 2.4G2 from detergent extracts of BMMC, digested with
      N-glycosidase F, subjected to SDS-PAGE, and immunoblotted with the Fc gamma RIIb1
      and Fc gamma RIIb1/b2-specific antibodies, BMMC were found to express Fc gamma
      RIIb1 and Fc gamma RIIb2. Selective immunoprecipitation of plasma membrane
      localized Fc gamma RIIb1 and Fc gamma RIIb2 from [3H]leucine-labeled BMMC showed
      that their ratio at the cell surface was similar to their initial biosynthetic
      ratio. Thus, in contrast to mature serosal mast cells that degranulate on binding
      of IgG complexes, immature mast cells, of which BMMC are a prototype, may have a
      role in the clearance of complexes without concomitant release of proinflammatory
      mediators.

PMID- 8283055
TI  - Granulocyte-macrophage colony-stimulating factor enhances 5-lipoxygenase levels
      in human polymorphonuclear leukocytes.
AB  - Stimulation of human polymorphonuclear leukocytes (PMNL) with granulocyte
      macrophage CSF (GM-CSF) results in the enhanced expression of several genes,
      including some coding for cytokines and enzymes. In this study, we investigated
      the ability of GM-CSF to up-regulate the human neutrophil 5-lipoxygenase (5-LO),
      a key enzyme in the leukotriene synthetic pathway. GM-CSF induced a dose- and
      time-dependent de novo synthesis of the 5-LO in PMNL, as determined by
      immunoprecipitation of 35S-methionine-labeled 5-LO. This up-regulation occurred
      within 30 min of treatment with GM-CSF and was observed using concentrations of
      GM-CSF as low as 30 pM. Prior treatment of the cells with the protein synthesis
      inhibitor cycloheximide abolished this effect of GM-CSF. Western blot analyses
      demonstrated that levels of 5-LO did not vary over a 6-h period in unstimulated
      PMNL treated with CX, and that GM-CSF induced a rapid increase in the total
      cellular level of 5-LO protein; taken together these results indicated a
      translational effect of GM-CSF on the expression of the 5-LO. However, GM-CSF did
      not significantly affect the level of 5-LO mRNA in neutrophils, as determined by
      Northern blot analysis. Furthermore GM-CSF did not alter the stability of 5-LO
      mRNA, in agreement with a posttranscriptional effect of GM-CSF on 5-LO expression
      in PMNL. These results show that human PMNL are capable of up-regulating the
      expression of the 5-LO in response to physiologic activation.

PMID- 8283056
TI  - Bacterial endotoxin regulation of cytokine receptors on murine bone marrow cells:
      in vivo and in vitro study.
AB  - Bacterial endotoxin (LPS) modulation of CSF-1, granulocyte-macrophage (GM)-CSF, G
      CSF, IL-1, TNF, and Kit Ligand receptors on murine bone marrow cells (BMC) in
      vivo and in vitro was investigated. In vivo LPS reduced the binding of hrIL-1 (>
      90%), mrTNF (> 62%), mrGM-CSF (> 42%) and hrG-CSF (> 91%) to BMC within 2 h, but
      elevated IL-1 binding (> 8.4-fold) between 8 to 48 h. In vitro, LPS decreased G
      CSF and IL-1 binding after 8 h yet increased TNF binding in a dose-dependent
      manner, suggesting that in vivo, the LPS up-regulation of IL-1 binding to BMC was
      indirect. Because in vivo LPS elevated the levels of TNF, IL-6, GM-CSF, and
      glucocorticoids, we further examined GM-CSF and TNF modulation of cytokine
      receptors on BMC in vivo. In vivo, TNF decreased the binding of TNF (> 88%), G
      CSF (> 89%), and IL-1 (> 73%) within 30 min, but increased IL-1 binding (> 4.8
      fold) after 10 h. In contrast, in vitro TNF decreased IL-1 binding after 8 h,
      implying that in vivo TNF up-regulation of Il-1 binding to BMC was also due to an
      indirect mechanism. However, GM-CSF increased IL-1 binding to BMC both in vivo
      and in vitro after 8 h. Further studies showed that in vitro GM-CSF and
      dexamethasone synergistically increased IL-1 binding to BMC in a time- and dose
      dependent manner. This synergistic modulation depended on synthesis of protein
      and mRNA, and was due to an increase in receptor number rather than an increase
      in receptor affinity. Because in vivo, LPS and LPS-induced cytokines (IL-1 and
      TNF) elicited the secretion of glucocorticoid and CSF activities, our results
      revealed a mechanism for LPS up-modulation of IL-1R on BMC in vivo.

PMID- 8283057
TI  - Leukotrienes in renal transplant rejection in rats. Distinct roles for
      leukotriene B4 and peptidoleukotrienes in the pathogenesis of allograft injury.
AB  - To investigate the role of leukotrienes in renal allograft rejection, we studied
      the effects of specific leukotriene inhibitors in a rat kidney transplant model.
      The enhanced renal production of leukotrienes observed in allograft recipients
      was reduced in a dose-dependent manner by the specific 5-lipoxygenase inhibitor
      MK886. This suppression of leukotriene production caused a substantial
      improvement in renal function. Inhibition of 5-lipoxygenase also reduced the
      severity of vascular inflammation and endothelial injury in allografts, and
      profoundly inhibited expression of donor MHC class II Ag on kidney cells.
      Survival of renal allograft recipients was prolonged from 10 +/- 1 days in
      controls to 16 +/- 1 days in animals that received a 6-day course of MK886 (p <
      0.05). To investigate the relative roles of LTB4 compared to peptidoleukotrienes
      in these processes, we treated a separate group of animals with the specific
      peptidoleukotriene receptor antagonist SKF106203. This agent inhibits the
      interaction of peptidoleukotrienes with their receptor(s) but does not affect the
      biologic actions of LTB4. In these studies, SKF106203 caused a modest improvement
      in renal allograft function that was of lesser magnitude than that seen with the
      5-lipoxygenase inhibitor. SKF106203 also reduced vascular inflammation in
      allografts, but had no effect on expression of MHC class II Ag. We conclude that
      leukotrienes play a key role in the pathogenesis of renal allograft rejection.
      Furthermore, the detrimental effects of leukotrienes in rejection are mediated by
      distinct actions of LTB4 and peptidoleukotrienes.

PMID- 8283058
TI  - Endogenous systemic IFN-gamma has a protective role against ocular autoimmunity
      in mice.
AB  - Locally produced IFN-gamma has been implicated in enhancing inflammation and in
      promoting organ-specific autoimmunity. In the present study, we investigated the
      influence of systemically available IFN-gamma on the expression of experimental
      autoimmune uveoretinitis (EAU) induced in mice with the retinal Ag,
      interphotoreceptor retinoid binding protein (IRBP). EAU-susceptible B10.A mice
      treated with a mAb to IFN-gamma developed much more severe EAU than did the
      controls and had increased delayed hypersensitivity (DH) responses to IRBP. There
      was an increase in the proportion of macrophage/monocytes vs lymphocytes in the
      ocular lesions of treated animals. The anti-IFN-gamma treatment did not prevent
      expression of MHC class II within the ocular tissues. Conversely, treatment with
      rIFN-gamma ameliorated EAU expression and lowered DH responses. This occurred
      despite widespread induction of MHC class II Ag in the ocular tissues and other
      organs. In contrast to EAU and DH, serum antibody titers and lymphocyte
      proliferation to IRBP were not significantly affected by either treatment.
      Experiments in several genetically resistant strains of mice showed that
      treatment with anti-IFN-gamma was able to up-regulate disease expression also in
      some EAU-resistant strains. In the case of one such strain, resistance to EAU
      induction was completely abrogated by the treatment. We conclude that
      endogenously produced IFN-gamma at the systemic level acts to down-regulate EAU
      in the mouse and that IFN-gamma-related mechanisms may be involved in conferring
      resistance to EAU in some mouse genotypes.

PMID- 8283059
TI  - Soluble Fc gamma RIIIa is present in plasma and is derived from natural killer
      cells.
AB  - Fc gamma RIII (CD16), a receptor for complexed IgG, is encoded by two very
      homologous genes: Fc gamma RIIIA and Fc gamma RIIIB. NK cells and macrophages
      express Fc gamma RIIIa, whereas only neutrophils constitutively express Fc gamma
      RIIIb. In a previous study we found that soluble (s)Fc gamma RIII in plasma
      seemed to originate only from neutrophils. However, CD16 mAb, directed against
      different epitopes of Fc gamma RIII, precipitated a glycoprotein from plasma of
      homozygous Fc gamma RIIIB gene-deficient donors. This glycoprotein migrated in a
      similar way as did released Fc gamma RIIIa derived from NK cells, whereas Fc
      gamma RIIIa released by cultured monocytes migrated differently and appeared to
      be more heavily glycosylated on SDS-PAGE. After deglycosylation, the M(r) of the
      plasma sFc gamma RIIIa was similar to that of released Fc gamma RIIIa. Moreover,
      V8-protease maps were identical. Therefore, we conclude that sFc gamma RIIIa is
      also present in plasma and is derived from NK cells. Because sFc gamma RIII
      levels are hardly detectable in the plasma of most homozygous Fc gamma RIIIB gene
      deficient donors, we suspect that the sFc gamma RIIIa level is negligible
      compared with the level of sFc gamma RIIIb in plasma of healthy donors. Two
      patients with an NK cell lymphocytosis had a high plasma level of sFc gamma
      RIIIaNK. Furthermore, high levels of sFc gamma RIIIaNK were found in plasma of
      two patients with rheumatoid arthritis. Thus, the level of sFc gamma RIIIaNK
      might reflect either an increase in circulating NK cells or an enhanced release
      of Fc gamma RIIIaNK in certain diseases. This study shows that an assay that
      discriminates between sFc gamma RIIIa and sFc gamma RIIIb is necessary for the
      interpretation of sFc gamma RIII levels in patients.

PMID- 8283060
TI  - IL-6-anti-IL-6 autoantibody complexes with IL-6 activity in sera from some
      patients with systemic sclerosis.
AB  - Anti-IL-6 IgG autoantibodies, often found in sera from patients with systemic
      sclerosis, may increase to the level sufficient to bind significant amounts of IL
      6 in serum. In our study of the role of anti-IL-6 autoantibodies in serum, we
      found that some sera with the autoantibodies possessed considerably higher IL-6
      levels (more than 100 pg/ml) compared with most of sera without the
      autoantibodies. Size-exclusion HPLC of the sera with these autoantibodies
      demonstrated that a significant part of the serum IL-6 activity was attributable
      to circulating IL-6-anti-IL-6 autoantibody complexes. Gel filtration of IL-6-anti
      IL-6 IgG complexes made in vitro by incubation of rIL-6 and IgG purified from the
      autoantibody-positive sera demonstrated that the complexes at 200 to 250 kDa were
      dominant ones and that IL-6 bound to the autoantibodies retained more than 60% of
      the original IL-6 activity. Moreover, IL-6-anti-IL-6 autoantibody complexes were
      shown to bind to recombinant soluble IL-6 receptors. Estimated affinity of anti
      IL-6 IgG autoantibodies from two patients was fairly high (4.2 x 10(9) to 3.3 x
      10(10) L/M). Therefore, the retention of IL-6 activity by IL-6-anti-IL-6
      autoantibody complexes may be explained by intact receptor-binding sites on the
      autoantibody-bound IL-6 molecules. Taken together, these results suggest that the
      properties of anti-IL-6 autoantibodies are consistent with a potential role as
      specific carriers for IL-6 in the circulation.

PMID- 8283061
TI  - Induction of IL-6 gene expression in Kaposi's sarcoma cells.
AB  - IL-6 is a multifunctional cytokine that functions as an autocrine growth factor
      for AIDS-derived Kaposi's sarcoma (KS) cells. We report that IL-6 is highly
      inducible at both the mRNA and protein levels in cultured KS cells by multiple
      agents, yet the effect of the IL-6 on the proliferation of KS cells is dependent
      on the agent responsible for its induction. Both IL-1 beta and the synthetic
      dsRNA, poly (I:C), induced high levels of IL-6 mRNA and protein expression,
      whereas LPS and TNF-alpha led to only modest increases in IL-6 protein and mRNA.
      When KS cells were incubated with poly (I:C) in combination with either IL-1 beta
      or TNF-alpha, there was a synergistic increase in the level of IL-6 production,
      whereas LPS and TNF-alpha in combination led to only an additive increase in the
      level of IL-6 production. Exogenous IL-6 was shown to induce proliferation in KS
      cells, yet there was a dramatic inhibition of proliferation in response to poly
      (I:C), despite the high levels of IL-6 produced. This inhibition of proliferation
      by poly (I:C) was unlikely as a result of expression of class I IFN in response
      to the poly (I:C) because high concentrations of exogenous IFN-alpha had no
      demonstrable effect on [3H]TdR incorporation under conditions in which poly (I:C)
      caused a 90% decrease in [3H]TdR incorporation. Pretreatment of KS cells with
      poly (I:C) for 24 h followed by removal of the poly (I:C) led to high levels of
      IL-6 secreted into medium that induced proliferation in KS cells. These data
      suggest that in vivo, multiple agents that occur in response to infection and
      systemic disease could induce IL-6 production by KS cells, yet the ability of the
      IL-6 to influence proliferation of KS cells is dependent on the context in which
      the IL-6 is induced.

PMID- 8283062
TI  - In vivo effect of delipidified cell component of Mycobacterium leprae in relation
      to infection with leprosy bacteria in mice.
AB  - The delipidified cell component (DCC) of Mycobacterium leprae was used as an
      immunomodulatory agent in Swiss white mice. The peritoneal macrophages of these
      mice were activated to produce increased amount of reactive oxygen intermediates
      like hydrogen peroxide (H2O2) and superoxide. These macrophages also attained the
      ability to kill M. Leprae in vitro as shown by several assay systems including
      the conventional mouse foot-pad technique. The increased levels of superoxide
      seem to be responsible for the killing of M. leprae as addition of the enzyme
      superoxide dismutase, which breaks down O2, resulted in survival of these bacilli
      inside the macrophages. The increased production of H2O2 does not seem to be
      responsible for killing M. leprae. The results indicate that the DCC of M. leprae
      acts as an effective immunomodulator in mice leading to the activation of
      macrophages with increased production of H2O2 and superoxide as well as enabling
      them to kill M. leprae via the action of superoxide anions.

PMID- 8283063
TI  - Bacillaemia and Mycobacterium leprae cell wall antigen in paucibacillary leprosy.
AB  - A study was undertaken to estimate bacillaemia and M. leprae antigen detection in
      54 paucibacillary leprosy patients (TT, BT). Acid-fast bacilli were detected in
      the blood of 14.8% patients of borderline tuberculoid (BT) leprosy. M. leprae
      antigen was demonstrated in 48.2% patients of BT leprosy. Slit-skin smears were
      negative in all these patients. At the end of treatment (6 months of WHO-MDT) all
      the follow-up blood samples were negative for both bacillaemia and M. leprae
      antigen in the serum.

PMID- 8283064
TI  - Sample survey of leprosy after three years of MDT in Bhavani taluk of Periyar
      District, Tamilnadu.
AB  - A sample survey of Bhavani taluk was undertaken in March 1992 three years after
      the introduction of MDT. Ten percent of the population was taken for the sample.
      A population of 45,781 was enumerated and 41,554 was examined. The three sectors
      were stratified according to the prevalence rate and classifying the villages by
      the size of the population. Villages were selected by random sampling. The sample
      survey detected 288 new cases of leprosy of which 16 (5.55%) were
      bacteriologically positive for acid-fast bacilli. The child rate was 13.54% among
      new cases. According to the sample survey the current prevalence rate per 1000
      population was 9.07 (with a new case detection rate of 6.93/1000 population),
      much higher than that derived from programme data (prevalence rate 3.45) and the
      expected ten fold reduction of prevalence under MDT. Independent sample surveys
      of NLEP units after three to five years of implementation of MDT will help to
      assess deficiencies in the programme and enable us to take remedial measures.

PMID- 8283065
TI  - Malignant transformation of plantar ulcers in leprosy.
AB  - Malignant transformation of plantar ulcers in leprosy is not uncommon. The
      apparent rarity of these neoplasms could be because many observed cases are not
      reported. To determine the extent of the problem, 133 consecutive cases of
      plantar ulcers seen over two years were studied clinically as well as
      histologically. Plantar ulcers were more common in the distal third of foot
      (64.67%) but malignant transformation was seen more often in plantar ulcers of
      proximal third of foot (64.29%). Malignant transformation was more common in
      plantar ulcers of long duration. Histologically, most of the lesions were benign,
      being instances of pseudo-epitheliomatous hyperplasia (57.89%) or atypical pseudo
      epitheliomatous hyperplasia (13.53%). However, squamous cell carcinoma was
      observed in 10.53% cases. Thus it may be that more cases with this complication
      will be detected if it is borne in mind that malignant change may be encountered
      in such ulcers.

PMID- 8283066
TI  - Disability pattern amongst leprosy cases in an urban area (Calcutta).
AB  - In a retrospective study of 1,264 leprosy cases, registered during 1987-1992, 282
      were found to have disabilities giving a disability rate (DR) 22.31% and 150 of
      them were also found to have deformities, giving a deformity rate 11.9%. Mean
      disability index (DI) was found to be 1.17. Disability rate (DR) significantly
      increased with age and the highest rate was 52.75% in lepromatous (L) cases,
      followed by 27.51% in borderline (N?L) and only 4.53% in nonlepromatous (N)
      cases. L cases had the highest deformity rate (22.25%) and N cases had the lowest
      DR (2.23%). DI was highest (1.46) in L, and lowest (0.52) in N cases. Males had
      significantly higher DR (27.2%) compared to females (13.0%). Deformity in hands
      (42.55%) was more common than in feet (22.70%). Increasing trend of DI was
      noticed with increasing duration of disease in L and N?L types. The number of
      nerves involved was high (4.72) in L cases compared to other types. DI was
      highest (1.25) in patients engaged in occupations involving hard work.

PMID- 8283067
TI  - A pilot project on community based rehabilitation in south India--a preliminary
      report.
AB  - A pilot project on Community Based Rehabilitation was launched by the Hind Kusht
      Nivaran Sangh in South Arcot District of Tamil Nadu with the help of the
      Hemerijckx Rural Centre, Rawttakuppam on an experimental basis to assess the cost
      effectiveness and suitability of its application in other districts. Twenty cured
      disabled leprosy patients with grades 1 and 2 deformities from 17 villages were
      given training in trades like cycle repairing, tailoring, pesticides spraying,
      doll making, cane work, cigar making, fish net knitting and incense stick making.
      The duration of the training varied from two to six months depending upon the
      trade. Local artisans and craftmen from among the community members were
      identified, motivated, and utilised as trainers. The travel and maintenance costs
      paid to the trainees was an incentive to learn the trade and the honorarium paid
      to the trainers motivated them to spare their time to impart the skill within the
      specified period. On completion of training, start-up funds needed for purchase
      of tools and accessories required for pursuing the vocation were arranged through
      banks under DRI scheme, IRDP schemes from BDO office and from other voluntary
      agencies. The total expenditure incurred for training 20 cured disabled leprosy
      patients worked out to only Rs. 25,350/-i.e., approximately Rs.1,250/- per
      patient. Out of the 20 patients trained, 17 have already started earning through
      the skills imparted to them.

PMID- 8283068
TI  - Group specific component (Gc) in erythema nodosum leprosum (ENL).
AB  - The distribution of phenotypes of group specific component (Gc) was examined in
      71 lepromatous leprosy (LL) patients without any history of ENL reaction and 65
      LL patients with history of frequent episodes of ENL reaction. The distribution
      of none of the phenotypes of Gc (Gc 1-1, Gc 2-1, Gc 2-2) was statistically
      significant among these groups.

PMID- 8283069
TI  - Improving NLEP performance in a low endemic area.
AB  - New innovative strategies of the medical officer of an upgraded urban leprosy
      centre of a low endemic state (Punjab) resulted in an increase in new case
      detection by seventy-four percent. Indigenous patients were much more regular
      than immigrant patients in colonies. The number of new indigenous punjabi
      patients has not shown any decline in last one decade, probably because of
      deficiencies in the functioning of NLEP. It is suggested that improved case
      detection by adopting strategies used by the authors and restricting free
      migration of untreated and partially treated patients would help in achieving the
      goals of NLEP.

PMID- 8283070
TI  - Facial, glossopharyngeal, vagus and hypoglossal nerve palsy in a case of
      lepromatous leprosy.

PMID- 8283071
TI  - Solitary neurofibroma mimicking nerve abscess.

PMID- 8283072
TI  - Fixed drug eruption due to rifampicin.

PMID- 8283074
TI  - Simple continuous system for reporting BI.

PMID- 8283073
TI  - Towards an evolving consensus on leprosy bacillus.

PMID- 8283075
TI  - The role of tumor necrosis factor-alpha in the aggravation of cerulein-induced
      pancreatitis in rats.
AB  - Severe acute pancreatitis is often complicated by intraperitoneal infection,
      resulting in multiple organ failure (MOF). It is known to elevate serum tumor
      necrosis factor (TNF-alpha) in patients with sepsis and/or MOF. In order to study
      the role of TNF-alpha in the aggravation of acute pancreatitis, we investigated
      TNF-alpha production by peritoneal macrophages in acute pancreatitis rat using
      the cerulein-induced pancreatitis model. TNF-alpha production by isolated
      peritoneal macrophages following lipopolysaccharide (LPS) stimulation was
      significantly increased in pancreatitis rats as compared with nonpancreatitis
      control rats (p < 0.001). Serum TNF-alpha activity was elevated following
      intraperitoneal administration of LPS as the septic challenge both in
      pancreatitis rats and in control rats, being significantly higher in the former
      (p < 0.05). Histological findings and liver function tests revealed that LPS
      induced more severe liver damage in pancreatitis rats than in control rats within
      24 h after LPS administration. These results indicate that increased TNF-alpha
      production by peritoneal macrophages in acute pancreatitis augmented LPS-induced
      liver injury and suggest the possibility that TNF-alpha may play a role in the
      development of MOF during acute pancreatitis complicated by intraabdominal
      sepsis.

PMID- 8283077
TI  - The point mutation of c-Ki-ras at codon 12 in carcinoma of the pancreatic head
      region and in intraductal mucin-hypersecreting neoplasm of the pancreas.
AB  - In order to clarify whether the detection of a point mutation in the c-Ki-ras
      gene at codon 12 in tumor tissues can assist in predicting the tumor's biological
      grade of malignancy, two types of tumors were investigated; one was called
      "carcinoma in the pancreatic head region," and the other was intraductal mucin
      hypersecreting neoplasm of the pancreas (IMHN). Dot hybridization and a modified
      PCR technique developed by Haliassos et al. were employed. Among 16 cases of
      tumors in the pancreatic head region, the point mutation was detected with a high
      frequency only in pancreatic ductal cell carcinomas (five out of six cases,
      83.3%), but was not detected in extrahepatic bile duct carcinomas (0/5) or in
      ampullary carcinomas (0/5). In pancreatic ductal cell carcinomas, no relation was
      found between the occurrence of the point mutation and the histological type of
      the tumor. Among 20 cases of IMHNs, the point mutation was found in 11 cases
      (55%). No relation was found between the occurrence of the mutation and the size
      of IMHNs. However, as the grade of cell atypia increased, the frequency of the
      mutation tended to become higher. These results suggest that detection of this
      point mutation might be useful for distinguishing pancreatic ductal cell
      carcinoma from those of other origins in the pancreatic head region, and for the
      determination of the histopathological grade of malignancy in IMHNs.

PMID- 8283076
TI  - Clinicopathological features and prognostic significance of nucleoside
      diphosphate kinase/nm23 gene product in human pancreatic exocrine neoplasms.
AB  - Expression levels of nucleoside diphosphate (NDP) kinase/nm23 gene product in the
      surgically resected 59 human pancreatic exocrine neoplasms were examined
      immunohistochemically using antiNDP kinase antibody. Immunoreactivity for NDP
      kinase varied from one tumor to the other. Out of the 47 invasive pancreatic duct
      cell carcinomas examined, 31 (66%) tumors showed strong immunoreactivity for NDP
      kinase, whereas ten (83%) of 12 benign or less invasive tumors (in situ
      adenocarcinoma and mucin-producing tumor) showed negative or weak
      immunoreactivity (p < 0.01; Chi-square test). Overall survival of invasive
      pancreatic duct cell carcinomas with strong immunoreactivity for NDP kinase was
      poorer than those with negative or weak immunoreactivity (p < 0.03; generalized
      Wilcoxon test). Strong immunoreactivity for NDP kinase was associated with the
      type of histological differentiation, the presence of lymph node metastases (p <
      0.05, respectively; Chi-square test), and the number of argyrophilic nucleolar
      organizer regions (p < 0.01; Student's t-test). These results suggest that NDP
      kinase/nm23 gene product expression was positively associated with tumor
      aggressiveness and poor survival of patients in human pancreatic exocrine
      neoplasms. They also suggest that NDP kinase expression is related to cell
      proliferation activity represented by the number of argyrophilic nucleolar
      organizer regions. Therefore, examining the level of NDP kinase/nm23 gene product
      could serve as a marker for malignant potentiality of pancreatic exocrine
      neoplasms.

PMID- 8283078
TI  - Detection of c-Ki-ras point mutation from pancreatic juice. A useful diagnostic
      approach for pancreatic carcinoma.
AB  - Cytological diagnosis of pancreatic carcinoma sometimes poses difficulties in
      distinguishing malignant from benign cells. Recent molecular study of pancreatic
      carcinoma has revealed a very high incidence of a point mutation of the c-Ki-ras
      oncogene at codon 12 in this neoplasm. To take advantage of this technique for
      the diagnosis of pancreatic carcinoma, we attempted to amplify the c-Ki-ras gene
      from endoscopically obtained pancreatic juice by isolation of DNA and polymerase
      chain reaction (PCR) coupled with restriction fragment length polymorphism
      (RFLP). PCR was possible in approx 70% of the cases. A point mutation was
      nonradioisotopically detected in 4 of 6 pancreatic carcinomas and in one
      intraductal papillary neoplasm, whereas no mutation was detected in other cases.
      Thus, this method was thought to be useful for the diagnosis of pancreatic
      carcinoma.

PMID- 8283079
TI  - Pancreatic trophism in experimental liver cirrhosis.
AB  - Pancreatic trophism and pancreatic enzyme composition, and plasma levels of
      cholecystokinin, insulin, glucagon, and glucose in liver cirrhosis induced by
      chronic thioacetamide administration (0.02% in the drinking water for 12 mo) were
      studied in rats. Advanced liver cirrhosis was evident in all thioacetamide
      treated rats. The weight of the pancreas and its contents of DNA, protein,
      trypsinogen, chymotrypsinogen, proelastase, secretory trypsin inhibitor, and
      amylase were significantly increased as compared to the controls. The pancreatic
      secretory enzyme content changes showed a nonparallelism, characteristic of a
      cholecystokinin effect. Light and electron microscopy revealed a normal
      pancreatic architecture. Bioassayed plasma cholecystokinin levels in both fed and
      24-h-fasted cirrhotic rats were significantly higher than in the corresponding
      controls. The plasma glucose, insulin, and glucagon levels demonstrated
      hypoglycemic tendencies with a glucagon predominance. These findings indicate
      that advanced liver cirrhosis in the rat is accompanied by pancreatic hypertrophy
      and hyperplasia, which might be attributed, at least in part, to elevated
      circulating cholecystokinin levels.

PMID- 8283080
TI  - Secretin-cerulein test and fecal chymotrypsin concentration in children with
      intestinal giardiasis.
AB  - We studied six patients with giardiasis (five males, one female), median age 3.5
      yr (range 1-11) and 12 healthy control subjects (10 males, 2 females), median age
      3.5 yr (range 1-10). Intestinal biopsy and a contemporaneous secretin-cerulein
      test were performed in all patients, and fecal chymotrypsin was also assayed.
      Intestinal biopsy was normal in five of the six patients with giardiasis, whereas
      one of the six presented a partial atrophy of the intestinal villi. The secretin
      cerulein test (1 CU/kg of secretin + 75 ng/kg of cerulein) did not show any
      significant difference between values in the outputs of chymotrypsin, lipase,
      phospholipase, and bicarbonate obtained in patients and in controls; however, in
      the one patient with partial intestinal mucosal atrophy, all enzymatic activity
      levels were below the normal limit for our laboratory. Furthermore, the mean
      values of fecal chymotrypsin concentration did not differ between the two groups.
      Fecal chymotrypsin was also reduced in the patient with an abnormal secretin
      cerulein test; a second assay performed 3 mo after the suspension of treatment
      (Metronidazole), however, showed a normal chymotrypsin concentration.

PMID- 8283081
TI  - Somatostatin analog treatment of pancreatic fistulas.
AB  - In order to hasten healing of pancreatic fistulas, we have treated 11 men and one
      woman with octreotide, a long-lasting somatostatin analog. This agent was
      administered subcutaneously in doses of 0.05-0.20 mg, two to three times per day.
      Fistulas were secondary to pancreatic biopsy (1), pancreatic abscess drainage
      (2), operative injury (3), and blunt abdominal trauma (4). The two patients with
      fistulas secondary to pancreatic biopsy had outputs of 1000 mL/d. The patient
      with blunt trauma had pancreatic ascites, with outputs of 750 mL/d. The remainder
      had outputs of 100-250 mL/d for periods ranging from 1 wk to 11 mo. After
      octreotide administration, fistula output decreased from 360 +/- 347 mL/d to 110
      +/- 131 mL/d on the first day of therapy (p < 0.05) and to 44 +/- 72 mL/d on the
      seventh day (p < 0.05). Seven patients eventually closed their fistulas. Failure
      to achieve fistula closure with octreotide was secondary to pancreatic duct
      stenosis (4); pseudocyst (1) or recurrent sepsis (4); and patient noncompliance
      (4). Somatostatin analogs are useful in the management of pancreatic fistulas.
      They significantly decrease (p < 0.05) the volume of fistula output, and they
      seem to aid fistula healing. Somatostatin analogs are safe even for outpatient
      management of pancreatic fistulas.

PMID- 8283082
TI  - CT of Clonorchis Sinensis pancreatitis.
AB  - Clonorchis Sinensis infestation can involve the pancreatic duct and induce
      attacks of acute pancreatitis. Ct findings in a case of Clonorchis Sinensis
      pancreatitis revealed significant enlargement of the pancreas with compression
      and obstruction of the common duct. Medical treatment leads to resolution of the
      clinical and CT findings. The patient experienced a second episode of
      pancreatitis 3 yr later. CT examination documented the development of chronic
      pancreatitis with an acute exacerbation.

PMID- 8283083
TI  - Solid and cystic tumor of the pancreas occurring without cyst formation in an
      adult male.
AB  - A solid and cystic tumor (SCT) of the pancreas occurring in a 35-yr-old male is
      reported. Cut sections of the specimen revealed a solid, ill-defined mass
      measuring 2.5 x 2.3 x 2.0 cm, without cystic or necrotic changes. Histologically,
      the solid tumor consisted of small, round acidophilic cells invading the
      surrounding pancreatic parenchyma. The tumor cells were positive for alpha-1
      antitrypsin and neuron-specific-enolase. Ultrastructural studies revealed clear
      nuclei with no zymogen, but immature secretory granules in the cytoplasm of the
      tumor cells, which had a junctional complex-like structure. These findings were
      consistent with the so-called solid and cystic tumor of the pancreas. There was
      neither a capsule surrounding the tumor nor a papillary structure, known to be
      characteristic findings of the SCT tumor. The small tumor reported in the present
      article might represent an early-stage SCT of the pancreas.

PMID- 8283084
TI  - Surgical options in chronic pancreatitis.
AB  - Chronic pancreatitis is primarily a medical disease but surgery is indicated to
      treat complications, rule out malignancy, and ameliorate intractable pain. The
      ideal operation for chronic pancreatitis would relieve this pain while preserving
      exocrine and endocrine function. No one procedure achieves these goals in all
      patients so surgeons must tailor their operations to individual patient needs. In
      patients with a dilated pancreatic duct, complete ductal decompression with a
      lateral pancreaticojejunostomy is usually indicated. Pancreatic resection is
      useful in patients with localized disease, nondialated ducts, or in whom cancer
      cannot be ruled out. More rigorous documentation of the type and outcome of
      therapeutic interventions for chronic pancreatitis and the patient populations to
      whom they are applied is needed. Subjective measurements must be replaced by
      objective findings so that the true benefits of these procedures can be better
      assessed and compared.

PMID- 8283085
TI  - [Postoperative lung function in patients with funnel chest].
AB  - We evaluated the postoperative lung function determined by spirometry in 54
      patients with funnel chest (48 males and 6 females: age range, 4-18 years).
      Thirty-one patients had sternal turnover as corrective surgery, while 23 had
      sternal elevation with absorbable PLA (polylactic acid) strut. The mean value of
      vital capacity as a percentage of predicted (%VC) was 97.3% before operation. %VC
      was decreased at 3 months (80.5%), 6 months (87.4%), 12 months (82.8%), 24 months
      (85.9%), and 36 months (77.7%) after the operation (p < 0.01). In patients who
      had sternal elevation, %VC was decreased at 3 months but not at 6 months, 12
      months, 24 months, or 36 months after the operation, while %VC was decreased at
      any point after the operation in patients who had sternal turnover. No
      significant changes were seen in forced expiratory volume in one second as a
      percentage of predicted (FEV1.0%), nor in the ratio of residual volume to total
      lung capacity (RV/TLC). In conclusion, sternal elevation with PLA strut is a
      better corrective surgery for funnel chest than sternal turnover, because of its
      less lung function loss after the operation.

PMID- 8283086
TI  - [Experimental study on heparin-free cardiopulmonary bypass using nafamostat
      mesilate (FUT-175) and heparin-coated circuit].
AB  - We investigated whether the combination of a new synthetic protease inhibitor,
      nafamostat mesilate (FUT-175), and heparin-coated cardiopulmonary bypass (CPB)
      circuit can achieve heparin-free CPB in rabbits. Nine rabbits underwent 2 hours
      of CPB with heparin-coated circuits. In 4 rabbits (FUT-Group), FUT was
      administered before (2 mg/kg in bolus) and during (5 mg/kg/hr continuously) CPB.
      In 5 rabbits (Heparin-Group), heparin was given before (4 mg/kg) and at 1 hour (2
      mg/kg) of CPB. Activated clotting time, activated partial thromboplastin time and
      fibrin degradation products showed no significant differences between the two
      groups during CPB. However, prothrombin time was significantly (p < 0.05) shorter
      in FUT-Group than in Heparin-Group. Platelet counts in FUT-Group was
      significantly lower than Heparin-Group. Massive clots were observed in all of the
      venous reservoirs of FUT-Group after CPB, whereas there were no major clots in
      Heparin-Group. The occlusion rate of hollow fibers of the oxygenators was
      significantly higher in FUT-Group (55 +/- 25%, mean +/- SD) than in Heparin-Group
      (14 +/- 12%). We concluded that heparin-free CPB with FUT and heparin-coated
      circuit is difficult in rabbits because activation of the extrinsic coagulation
      cascade cannot be sufficiently suppressed by FUT.

PMID- 8283087
TI  - [Coronary artery bypass surgery in patients older than 75 years of age].
AB  - There is controversy whether the short-term and long-term results of coronary
      artery bypass surgery in elderly patients justify the commencement of the
      procedure. Between February 1988 and July 1992, 113 patients underwent CABG in
      our hospital, of whom 15 (13.3%) patients were 75 years old or older (mean 76
      years). They consisted of 5 men and 10 women, and all were in New York Heart
      Association class III or IV. Unstable angina was observed in 13, left main trunk
      stenosis was in 4, and left ventricular dysfunction, ejection fraction of less
      than 0.30 was in 2 of 15 patients. The mean number of bypass grafts was 2.7 per a
      patient, and only autologous greater saphenous vein was used. In seven (47%)
      cases, CABG was performed urgently or emergently. There was neither operative nor
      hospital death, although some complications occurred in 11 (73%) patients. Post
      operatively, 13 patients were in NYHA class I and 2 in class II. Only one patient
      died of pneumonia one year after operation. Although high risks of operative
      mortality and morbidity with coronary artery bypass surgery for elderly patients,
      particularly in urgent or emergent cases, had been reported, the long-term
      survival rate and freedom from angina were excellent, justifying continuous
      commencement of coronary bypass surgery in the selected patients over 75 years of
      age.

PMID- 8283088
TI  - [Primary mediastinal tumors in children--comparison with mediastinal tumors in
      adults].
AB  - During the past 43 years, 628 patients with a primary mediastinal tumor underwent
      surgical operation in our institution. Of those patients, 106 patients (16.9%)
      were children of 15 yr of age or less and 522 patients (83.1%) were adults. 47
      (44.3%) of the 106 children had neurogenic tumors, while 21 patients (19.8%) had
      a teratoma. 189 (36.2%) of the 522 adults had thymoma and 89 patients (17.1%) had
      teratoma. In the 106 children there were 71 benign tumor patients (66.9%) and 35
      malignant tumor patients (33.1%). There were 277 (53.1%) benign and 245 (46.95)
      malignant tumors in the 522 adults. The adults had significantly more malignant
      tumors than the children (p < 0.01). In our series of malignant mediastinal
      tumors in children, 14 patients (13.3%) had a lymphoma and 11 patients (10.5%)
      had a neuroblastoma. On the other hand, in the adults, 127 patients (24.3%) had a
      thymoma and 66 patients (12.6%) had a lymphoma. Regarding benign mediastinal
      tumors, in children, 30 patients (28.5%) had a ganglioneuroma and 19 patients
      (18.0%) had a teratoma. In the adults, 68 patients (13.0%) had a teratoma and 62
      patients (11.9%) had a thymoma. In the clinical manifestation, 51 child patients
      (48.1%) and 191 adult patients (36.6%) were asymptomatic. As symptoms due to
      compression or direct invasion to adjacent structures, dyspnea was seen in 16
      child patients (15.1%), and chest pain occurred in 59 adult patients (11.3%).
      Dyspnea was significantly more common in children than in in adults (p < 0.01).
      Emergency operations were performed in children more than in adults.

PMID- 8283089
TI  - [Aortic arch reconstruction without aortic cross-clamping using separate
      extracorporeal circulation].
AB  - Between March 1991 and October 1992, 21 consecutive patients underwent aortic
      arch reconstruction without aortic cross-clamping using separate extracorporeal
      circulation in combination with retrograde blood cardioplegia (Non-clamping
      selective cerebral perfusion). Twelve patients had true arch aneurysm, 3 had
      acute aortic dissection and 6 had chronic aortic dissection including 2 redo
      cases. Cardiopulmonary bypass (CPB) was instituted with an arterial cannula in
      the femoral artery and 2 cannulae in both vena cavae. When tympanum temperature
      was lowered to 20 degrees C by central cooling, CBP was stopped temporarily. As
      soon as the aortic arch was incised longitudinally together with aneurysm,
      flexible 12 Fr. balloon cannulae were inserted into the three arch arteries via
      their orifices and selective cerebral perfusion was started. The perfusion flow
      was kept between 0.3 L/m2/min and 0.35 L/m2/min with the pressure of catheter tip
      from 30 to 60 mmHg to keep tympanum temperature 18 degrees C. Heart was protected
      by retrograde continuous cold blood cardioplegia. During arch correction, the
      descending aorta was occluded by a balloon then abdominal viscera were perfused
      via a femoral return cannula and rewarming to 25 degrees C was started to prevent
      visceral organ failure and coagulopathy. The time of separate perfusion ranged 20
      to 161 minutes with a mean of 99.9 minutes. Except one patient who died of
      pneumonia, 20 patient (95.2%) were discharged and doing well. No cerebral
      complication, myocardial infarction, lung bleeding and coagulopathy occurred. In
      order to prevent the infarction by debris and to protect vital organs, this
      method is reliable for aortic arch reconstruction.

PMID- 8283090
TI  - [Surgical results of postinfarction ventricular septal rupture].
AB  - Between 1981 and 1991, 17 consecutive patients underwent surgical repair of
      postinfarction ventricular septal rupture (VSR). 15 patients were operated upon
      during acute phase after the onset of VSR. Two patients were operated upon six
      weeks or more after the onset. Overall hospital mortality was 43% in the reviewed
      group. Our experience suggested that the number of the patients over 70 years of
      age increased and prevalence in VSR associated with the multivessel coronary
      artery disease was recognized. Despite improved surgical techniques and enhanced
      myocardial protection, our experience with surgical treatment of VSR was not as
      successful as we had hoped. Delay of operation is likely to produce hemodynamic
      instability and may increase operative mortality. In conclusion, the preoperative
      mechanical and pharmacological support should be performed, even if the patient
      is not so critically ill, and the earlier operation might lead to more favourable
      results in the surgery of the postmyocardial infarction ventricular septal
      rupture. In addition, preoperative coronary angiography for the precise
      evaluation of the coronary artery lesions might contribute to better results in
      the late phase of postoperative period.

PMID- 8283091
TI  - [Surgical treatment of the patients with pulmonary atresia, ventricular septal
      defect associated with major aorto-pulmonary collateral arteries--a report of two
      cases].
AB  - Two patients undergoing corrective operation for pulmonary atresia with
      ventricular septal defect associated with major aortopulmonary collateral
      arteries (MAPCAs) were reported. Both patients underwent staged surgical repair,
      first stage: unifocalization, and second stage: Rastelli type operation. Case 1
      was a 13-year-old female who had a confluent central pulmonary artery and 1
      MAPCA, unifocalized at 10 years of age. After the corrective operation, the ratio
      between peak right ventricular and peak left ventricular pressure (pRV/LV) was
      0.5 and she followed a satisfactory post-operative course. Case 2 was a 11-year
      old female who had a severe hypoplastic central pulmonary artery (3 mm in
      diameter) and 3 MAPCAs, and she underwent unifocalization twice. After the
      corrective operation, pRV/LV was 0.65 and her postoperative course was also
      satisfactory.

PMID- 8283092
TI  - [A successful surgical repair for all right pulmonary venous return and intact
      atrial septum associated with patent left superior vena cava].
AB  - A successful repair of total right pulmonary venous return and intact atrial
      septum associated with patent left superior vena cava (PLSVC) is reported. A 31
      year-old women was admitted for evaluation of heart failure. A heart murmur had
      been detected since her childhood without any subjective symptoms. She was
      diagnosed as partial anomalous venous return of all right pulmonary vein and
      intact atrial septum (IAS) associated with PLSVC by cardiac catheterization.
      Operative findings revealed that all right pulmonary vein connected to right
      atrium (RA) and superior vena cava (SVC), PLSVC drained into coronary sinous
      (CS), therefore RA, right ventricle and CS were enlarged, but SVC was small due
      to PLSVC. Through large incision from RA to SVC, atrial septum was opened 30 mm
      in diameter. Internal conduit using pericardial patch was made in order to drain
      anomalous pulmonary venous blood into left atrium through the ASD. Finally, SVC
      and RA were reconstructed by pericardial patch for prevention of conduit
      obstruction. One month after operation, no stenosis of SVC and right pulmonary
      vein was evidenced by cardiac catheterization and all through the postoperative
      course, arrhythmias did not detected. She was discharged with uneventful
      postoperative course.

PMID- 8283093
TI  - [Heart failure due to severe myocardial calcification--a rare complication after
      irradiation on the chest wall].
AB  - A 28-year-old female who had had irradiation on the chest wall at the age of 5 as
      a remedy for keroid granulation after burn, recently developed congestive heart
      failure. Severe tricuspid regurgitation was demonstrated by echocardiography with
      a certain calcification in the cardiac shadow on chest radiogram. Calcified right
      ventricule and ventricular septum were noticed operatively, which disturbed
      ventricular motion and also caused tricuspid valve deformity. These calcified
      myocardium apparently corresponded with the irradiation field. After tricuspid
      valve replacement, she regained physical activity satisfactorily without
      congestive heart failure. Because she had no other known causes of cardiac
      calcification such as hypercalcemia, myocarditits, myocardial infarction or renal
      diseases, irradiation on the chest wall could be responsible for the severe
      myocardial calcification.

PMID- 8283094
TI  - [A case report of primary malignant hemangiopericytoma of the chest wall].
AB  - We described a very rare case of malignant hemangiopericytoma of the chest wall,
      which was surgically resected. The patient, a 50-year-old woman, came to our
      hospital because of an abnormal shadow in the right chest wall of X-ray film
      without any symptom. The diagnosis of hemangiopericytoma was made with
      preoperative cytologic examination by means of transcutaneous aspiration biopsy.
      The tumor was a 47 x 36 x 25 mm, round and sessile mass originating from the 5th
      intercostal tissue without pulmonary adhesion, and the patient underwent en bloc
      resection of the tumor with the 16 x 12 mm sized chest wall including the 4th,
      5th and 6th ribs. Pathological diagnosis was malignant hemangiopericytoma.
      Postoperative course was uneventful, and the patient is now doing well without
      local recurrence and distant metastasis for 11 months after the operation. We
      reviewed 8 cases of this tumor reported in the Japanese literatures.

PMID- 8283095
TI  - [A case of coronary artery bypass grafting (CABG) with acquired
      tracheobronchomalacia].
AB  - Acquired tracheobronchomalacia is often overlooked because the symptoms are
      similar to those of chronic obstructive lung disease. A 55-year-old man underwent
      an emergency CABG because of unstable angina pectoris. CABG was performed
      uneventfully. On the third day after operation, severe cough and dyspnea were
      persisted, followed by the episode of ventricular fibilliration. Cardiopulmonary
      resuscitation was necessary. CT scan of the chest showed crescent narrow
      deformity from the lower trachea to the right main bronchus. Bronchoscopic
      examination revealed 90% stenosis of the trachea during coughing, and edematous
      tracheal mucosa. Acquired tracheobronchomalacia is an illness of the middle-aged
      and the elderly and tends to be progressive. Recently, because the patients for
      CABG have become older, tracheobronchomalacia should be taken into consideration.

PMID- 8283096
TI  - [A case of cervical teratoma in adult].
AB  - Cervical teratomas are rare neoplasms in adults. A 21-year-old male was admitted
      to our hospital for evaluation of a cervical tumor. CT scan and MRI showed the
      tumor extended into the mediastinum and not invaded to surrounding tissue. 201T1
      scintigram showed increased uptake in the tumor. The tumor was resected with
      coller incision and median sternotomy. Histological examination revealed mature
      teratoma. The patient remains free of disease one year and seven months after
      operation.

PMID- 8283097
TI  - [A successful mitral valve replacement for infective endocarditis with mitral
      valve aneurysm].
AB  - We reported a rare case of mitral valve aneurysm. The patient was a 67-year-old
      woman with regurgitation of mitral and aortic valve due to infective
      endocarditis. Preoperative two-dimensional echocardiogram revealed a aneurysmal
      change and prolapsing on anterior mitral leaflet. Left ventriculogram showed
      mitral regurgitation of Sellers IV. She underwent mitral valve replacement with
      27 mm Carbo Medicus prosthesis successfully. There was a perforated valvular
      aneurysm (21 x 15 x 11 mm) and inflammatory cleft on anterior mitral leaflet at
      histopathological findings. The pathogenesis of mitral valve aneurysm was
      generally infective endocarditis and rarely congenital anomaly, syphylis,
      Aortitis syndrome, or Marfan syndrome. Mitral valve replacement was a procedure
      of choice for mitral valve aneurysm, which is especially large, perforated and
      severely inflammatory one.

PMID- 8283098
TI  - [A case report of surgical treatment of ruptured coronary artery aneurysm].
AB  - A 63-year-old women experienced acute heart failure due to a ruptured aneurysm
      resulting from the coronary artery fistula which originated from the left
      anterior descending artery. On surgery, the pericardial cavity was found filled
      with massive hemorrhagic fluid and perforation was detected on the surface of the
      aneurysm, sphere-shaped with a approximate diameter of 50 mm. Operation was done
      by closure of fistula and subsequent aneurysmectomy under extracorporeal
      circulation. Post operative course had been uneventful. Coronary artery fistula
      accompanied with aneurysm had been thought to have a high risk of rupture and to
      be in indication of surgical intervention. This case report was undertaken with
      bibliographical consideration, since there had been only a few reports of actual
      ruptures.

PMID- 8283099
TI  - [A successful repair of anomalous origin of right pulmonary artery from ascending
      aorta complicated with subdural hematoma, MRSA infection and postoperative
      intestinal perforation].
AB  - A 2-month-old male infant with anomalous origin of right pulmonary artery from
      ascending aorta who had subdural hematoma and MRSA infection due to the
      hemodynamic deterioration after cardiac catheterization was reported. The cardiac
      anomaly was successfully corrected by bypass grafting between the right pulmonary
      artery and the pulmonary trunk with an expanded polytetrafluoroethylene tube.
      This procedure without cardiopulmonary bypass was selected because of the
      presence of subdural hematoma and poor general conditions, and no signs of
      mediastinitis were noticed postoperatively in spite of the use of artificial
      material. But he had colostomy and drainage due to postoperative intestinal
      perforation. The complicated postoperative course of this patient recommends us
      the surgical correction of this anomaly without cardiac catheterization.

PMID- 8283100
TI  - [Tetralogy of Fallot with absent pulmonary valve--a successful surgical case at
      40 days after birth].
AB  - A markedly symptomatic patient with tetralogy of Fallot and absent pulmonary
      valve underwent operation at 40 days after birth. The baby had severe
      cardiopulmonary insufficiency at neonatal period and needed surgical
      intervention. The operation is consisted of patch closure of ventricular septal
      defect, partial resection of dilated pulmonary artery, and right ventricular
      outflow reconstruction with unicusped prosthetic patch. The patient is growing
      and is well more than 2 years and 8 months after operation.

PMID- 8283101
TI  - [Successful surgical repair for a patient with atrial septal defect and severe
      pulmonary hypertension--its surgical indication and prostaglandin E1 use for
      postoperative pulmonary hypertensive crisis].
AB  - A 45-year-old woman with atrial septal defect and pulmonary hypertension was
      admitted for surgical repair. Cardiac catheterization data revealed pulmonary to
      systemic flow ratio (Qp/Qs) of 1.81, pulmonary artery pressure (PAP) of 82/30
      mmHg and pulmonary vascular resistance (PVR) of 10.8 unit. Open lung biopsy was
      added to evaluate pulmonary vascular obstructive disease (PVOD) which was shown
      Heath-Edwards grade 3 PVOD. Following closure of the defect, PAP (systolic)
      exceeded momentarily systemic level after cardiopulmonary bypass. Prostaglandin
      E1 drip was remarkably effective to bring down PAP during early postoperative
      period. Although PAP has not been shown significant decrease on catheterization
      of one year after surgery, great symptomatic improvement has been achieved.

PMID- 8283102
TI  - [A successful repair of tetralogy of Fallot with aortic valve regurgitation,
      coronary artery-pulmonary artery fistula and absent pulmonary valve in a 54-year
      old man].
AB  - A 54-year-old man suffered from tetralogy of Fallot associated with aortic valve
      regurgitation, coronary artery-pulmonary artery fistula and absent pulmonary
      valve underwent intracardiac repair. The operation was completed with ligation of
      the fistula, aortic valve replacement using a SJM 27 A, patch closure of
      ventricular septal defect (perimembranous outlet type) and right ventricular
      outflow reconstruction using a large transannular monocusped-patch, 4 cm x 6 cm
      in size. Postoperative course was uneventful and he is doing well now. There was
      no previous reports about TOF associated with AR, the absent pulmonary valve and
      the coronary anomaly in the adults in the literature.

PMID- 8283103
TI  - [Right ventricular myxoma with near obstruction of the pulmonary artery].
AB  - Right ventricular myxoma is very rare. To our knowledge, only 23 cases in Japan
      have been reported in the literature. A 76-year-old male was admitted with
      complaints of cough and dyspnea. We found an abnormal floating mass in the right
      ventricular outflow tract by echocardiography and cineangiocardiography. The
      digital subtraction angiography showed that the following mass continuously
      lodged in the pulmonary artery with total occlusion of the left main pulmonary
      artery and near obstruction of the right pulmonary artery. Furthermore he had the
      constitutional signs of myxoma and the serum IL-6 level reached 41.7 pg/ml. Under
      extra-corporeal circulation, we salvaged the right ventricular outflow tract to
      the right lung, resecting the tumor, originated from the right ventricular septum
      and extended to bilateral main pulmonary arteries.

PMID- 8283104
TI  - [A case report of complex cardiac malformation treated with total cavopulmonary
      connection after pulmonary artery banding].
AB  - A two-year-old boy with cardiac malformation including hypoplastic right
      ventricle, severe stenosis of the tricuspid valve, atrial primum defect and
      ventricular septal defect underwent total cavopulmonary connection after
      pulmonary artery banding, which was done to tract cardial failure at six months
      after birth. Under cardiopulmonary bypass, an intraatrial cavocaval channel was
      constructed with a prosthetic patch of expanded polytetrafluoroethylene (EPTFE).
      The superior vena cava was transected and each end of the superior vena cava was
      anastomosed to the pulmonary artery in an end-to-side fashion. Pulmonary artery
      pressure registered 15 mmHg on cardiac catheterization after operation, and
      angiography showed smooth blood flow to the pulmonary artery from the vena cava.
      We suggest that a Fontan-type operation could be indicated for the patients
      younger than 4-year-old having acceptable pulmonary resistance if the symptoms of
      hemoconcentration and hypoxia are life-threatening.

PMID- 8283105
TI  - [Extended tricuspid valve excision for active infective endocarditis associated
      with ventricular septal defect].
AB  - We report a patient of ventricular septal defect associated with a vegetations on
      the tricuspid valve and a perforation of the aortic cusp caused by infective
      endocarditis. Antibiotics could not relieve the high fever of this patient, and
      disseminated intravascular coagulation caused by sepsis and two-sided heart
      failure developed. She underwent extended tricuspid valve excision, aortic valve
      replacement and VSD closure during the active stage. Post-operative antibiotic
      therapy was continued intravenously for 6 weeks, and orally for 3 more weeks.
      Although post-operative right ventriculography indicated tricuspid regurgitation
      and right atrium enlargement, pressure study of the right side of the heart
      revealed normal hemodynamics.

PMID- 8283106
TI  - [Six cases of traumatic diaphragmatic hernia].
AB  - In recent 3 years, six cases of diaphragmatic hernia caused by blunt trauma were
      treated surgically. Traumatic mechanics, appearance of rupture, associated
      injury, diagnostic procedure and surgical treatment are reviewed. All of them
      were survived with immediate surgical repair. Thoracoscopy is so useful to
      diagnose the right sided diaphragmatic hernia.

PMID- 8283107
TI  - [A case of liver hernia protruded from the central tendon of the right
      diaphragm].
AB  - Diaphragmatic hernia is a rare disease. And if the contents of hernia are
      intestines, the diagnosis is easy. But if those are great omentum or liver,
      discrimination from the thoracic tumor is difficult. We experienced a case of
      liver hernia protruded from the central tendon of the right diaphragm. A 6-year
      old girl was admitted to our hospital for investigation of an abnormal shadow of
      the right lower lung filed, pointed out in the chest X-ray examination at school.
      We diagnosed as a congenital diaphragmatic hernia of the liver. We made a
      surgical correction and her postoperative course was uneventful.

PMID- 8283108
TI  - [A case of surgical correction of sinus venosus atrial septal defect, mitral
      cleft, and interruption of inferior vena cava with azygos continuation in viscero
      atrial heterotaxic syndrome].
AB  - A successfully corrected case of a 39-year-old female with viscero-atrial
      heterotaxic syndrome was reported. The cardiovascular anomalies were sinus
      venosus atrial septal defect, mitral cleft, and interruption of inferior vena
      cava with azygos continuation. She also had bilateral bilobed lungs, symmetric
      liver, right sided stomach, and malrotation of the bowel, indicating left
      isomerism. The atrial septal defect was closed with Teflon patch and mitral cleft
      was repaired with direct suture of the cleft. The postoperative course was
      uneventful and mitral regurgitation was trivial postoperatively.

PMID- 8283109
TI  - [Atresia of the right coronary ostium associated with annulo-aortic ectasia--a
      case of successful surgical repair].
AB  - A case of a 51-year-old male with atresia of the right coronary artery and annulo
      aortic ectasia is described. He presented with heart failure and underwent open
      heart surgery. Preoperative aortography did not show the ostium of the right
      coronary artery. At surgery the right coronary ostium was not found on the
      intimal surface of the aneurismal aortic wall. A fine cord was attached to the
      adventitial surface of the anterior aortic root. A modified Bentall's procedure
      was performed to reconstruct the left coronary artery alone. The post-operative
      course was uneventful. It is speculated that the hypoplastic ostium of the right
      coronary artery was pulled up and formed a flap-like closure with increased
      expansion of the aorta.

PMID- 8283110
TI  - [Omental implantation technique for esophageal perforations--a clinical case and
      experimental studies].
AB  - We successfully used the omental implantation technique in a case of esophageal
      perforation in which simple closure was impossible because of extreme
      inflammatory changes. Although excellent results have been obtained by this
      method in gastroduodenal perforations, it has never been used before in cases of
      esophageal perforations. In this study we subsequently investigated the
      histological repair mechanism by carrying out animal experiments. Clinical case A
      59-year-old male entered our hospital with the symptoms of chest pain and fever
      after endoscopic therapy for esophageal obstruction by food impaction. He
      underwent an emergency thoracotomy 54 hours after endoscopy. A perforation of
      about 2 cm in diameter was observed in the subthoracic esophageal wall which
      become too weak to close by stitching. This perforation was filled with an
      omental plug inserted from the peritoneal cavity under laparotomy. The patient
      recovered and his perforated lesion was completely repaired. Animal experiment In
      10 hybrid adult dogs, omental implantation was performed on perforations of more
      than 1 cm in diameter in the subthoracic esophagus made by electric coagulation.
      One to four weeks postoperatively, these inserted omentums were observed
      endoscopically before sacrifice. The implanted omentums were endoscopically
      observed as elevated lesions after 2 weeks, but they became flat after 3 weeks
      and the mucosa seemed to be almost normal after 4 weeks. Histological
      investigation showed that the implanted omentums maintained their original
      structure accompanied by remarkable inflammatory changes 1 week
      postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283111
TI  - [Chordal reconstruction with polytetrafluoroethylene (PTFE) suture for mitral
      regurgitation caused by prolapsed anterior leaflet].
AB  - Cardiac surgeons have hesitated to perform valvuloplasty for MR caused by
      elongated or ruptured chordae of the anterior leaflet (AL) of the mitral valve.
      We experienced three cases of successful chordal reconstruction (CR) to the AL
      last year. Two of them were due to elongation of all chordae tendineae to the AL.
      Four CRs, one chordal shortening, cleft closure and ring annuloplasty (AP) were
      performed in one case, and 8 CRs to the AL, two to the posterior leaflet,
      commissural closure and ring AP in another. In the third case 2 CRs combined with
      Reed's AP, closure of ASD and tricuspid AP were performed. The MR disappeared in
      one case and improved to grade I in others postoperatively. NYHA classes improved
      from class III or IV to I or II postoperatively. The MRs have not increased 6 to
      12 months after the surgery. The CR with PTFE suture enabled to do the
      valvuloplasty for the chordal abnormalities of the AL without valve resection.
      This technique seems to be adequate for repairing a major prolapse of the AL
      caused by multiple chordal abnormalities.

PMID- 8283112
TI  - [Gait analysis of patients with osteoarthritis of the hip and those with total
      hip arthroplasty].
AB  - For the purpose of quantitative evaluation of gait after total hip arthroplasty
      (THA), the author performed gait analysis using a force plate and a light source
      spot-measuring device. In this study, the author laid emphasis on measuring the
      moments of the hip joint on the coronal and sagittal planes, using a rigid body
      link model. On the sagittal plane, an extension moment began to be noted in the
      early stance phase. This moment was lower in patients showing escape limping.
      Flexion moment appeared in the middle to late stance phases. This moment was
      lower in patients with restricted hip extension. On the coronal plane, an
      abduction moment appeared in the single stance phase. This moment was lower in
      patients showing Duchenne limping. Abnormalities in these moments were sometimes
      observed even in patients in whom distance-related factors, temporal factors, and
      floor reaction force curves had been normalized. Therefore, the measurement of
      hip joint moments is expected to facilitate the evaluation of the hip joint
      function itself, unmodified by the compensatory effects by other joints.

PMID- 8283113
TI  - [Dynamic roles of the upper extremity during axillary crutch gait].
AB  - To ambulate successfully with an axillary crutch, the upper extremities play an
      important part in supporting the body's entire weight. To evaluate the roles of
      the upper extremity during axillary crutch gait 15 normal adult subjects, 23
      patients with an affected single leg, and 3 patients with rheumatoid arthritis
      (RA), were investigated. The gait patterns using crutches were: the one-leg swing
      through crutch gait and three-point crutch gait for both normal subjects and
      patients with an affected single leg, and the three-point crutch gait for RA
      patients. The real-time motion analysis system "Quick-MAG", force plates, and a
      VTR system were used for data acquisition. The forces at the arm-pit and the
      hands during the swing-through crutch gait decreased when the cadence increased
      from 60 to 100 steps per minute. However, the floor reaction curve suggested
      distortion of the rubber at the crutch tip when the cadence reached 100. In the
      plane of progression during the crutch stance phase, the elbow flexion angle was
      about 14 degrees, and the wrist radial flexion angle about 23 degrees in the
      middle of the crutch stance phase. This position might be the best for efficient
      force exertion from the upper extremity. The unloading ratio during the three
      point crutch gait was 35 percent in the normal subjects, 49 percent in patients
      with an affected single leg, and 14 percent in the RA patients. The results of
      the unloading ratio, indicated that elbow and wrist joint impairment prevented
      the RA patients from sustaining enough posture to support body weight during the
      three-point crutch gait.

PMID- 8283114
TI  - [Simplified detection of RB gene mutation by PCR-SSCP method in human
      osteosarcoma].
AB  - The genome of retinoblastoma (RB) plays an important role in the regulation of
      cell-cycle and cell proliferation. The mutation of RB gene is capable of
      developing RB and the RB gene probably functions as a tumor suppressor gene in a
      physiological condition. In order to define if the mutation of RB gene occurs in
      osteosarcoma (OS), the present worker examined one case with hereditary RB and
      seven with primary OS by using PCR-SSCP (polymerase chain reaction-single strand
      conformation polymorphism) method with different primers from sequences of
      genomic RB gene (exon 19, 20, and 21). The results of this study indicated that
      there were two cases of OS with wide deletion, and one with point mutations which
      were present in the area of exon 20. From these findings, it was concluded that
      the PCR-SSCP method was simple and useful for the detection of mutations of RB
      gene.

PMID- 8283115
TI  - [Measurement of bone mineral density of metacarpal and phalangeal bones of the
      hand by dual X-ray absorptiometry].
AB  - Bone mineral density (BMD) of the metacarpal and phalangeal bones of the hand was
      evaluated using dual X-ray absorptiometry (DXA) in 104 healthy subjects, 35
      patients with rheumatoid arthritis (RA) and 6 young male volunteers with a short
      arm cast. BMD was positively correlated with the bone volume of metacarpal and
      phalangeal bones in skeletal specimens. In healthy subjects, the mean values for
      BMD of metacarpals of the index and middle fingers were significantly higher than
      those of the ring and little fingers (p < 0.001). The BMD of the middle proximal
      phalanx was the highest among the proximal phalanges. The BMD of the middle
      phalanges was the same pattern as in the proximal phalanges. There was no
      significant difference in the BMD of the distal phalanges between the fingers. In
      62 healthy women aged from 22 to 82 years, BMD was at its peak in the metacarpal
      and proximal phalangeal bones in their thirties, and in the distal phalanges in
      their forties. Thereafter, BMD decreased linearly with age. In contrast, age
      related changes in BMD were not shown in 42 healthy men aged from 22 to 76 years.
      BMD of the metacarpal and phalangeal bones in RA markedly decreased with disease
      stage. Four-week immobilization of the hand by a short arm cast affected BMD of
      the metacarpal bones in 6 healthy volunteers. The mean change in BMD was -4.1%
      after 4 weeks of immobilization, followed by a return to the initial value in 12
      weeks after removal of the plaster. We concluded that the bone mineral
      measurement of metacarpal and phalangeal bones could be useful for evaluation of
      age-related bone loss and the deterioration of bone in metabolic disorders.

PMID- 8283116
TI  - [Torsional strength of the epiphyseal plate and fracture patterns with aging
      (three-dimensional analysis with SEM)].
AB  - The tortional strength and fracture patterns of the proximal tibial epiphyseal
      plate in 4-, 8-, and 12-week-old rabbits were investigated (n = 11, 13 and 8,
      respectively). The strength was measured with a torsional machine, and then
      maximum torque, angular deformation and energy absorption were calculated from
      the load-deformation curve. The rotation axis was aligned to the long axis of the
      specimen, and a holding method for the specimen was devised to minimize
      positional error. The fracture surfaces were then examined both histologically
      and with three-dimensional scanning electron microscopy (SEM). The torsion test
      showed that maximum torque and energy absorption with the exception of angular
      deformation increased significantly with age. Histological examination by light
      microscope of sagittal sections passing through the midline of fragments revealed
      that epiphysiolysis commonly occurred between the calcification layer and the
      metaphysis in the anterior portion, as well as between the transitional part of
      the palisading layer and the hypertrophying layer in the posterior portion. These
      results indicate that epiphysiolysis is most likely to occur between adjacent
      layers with the greatest structural differences. Three-dimensional SEM
      micrographs revealed that fracture patterns became more varied as the torsional
      strength of the epiphyseal plate was increased with age. Additionally, SEM
      revealed that the density of the collagen network in the cartilaginous matrix
      surrounding cells in the proliferating layer also increased with age. One of the
      reasons for the increase in torsional strength is related to a morphological
      change such as the development of three-dimensional wave-like structure of
      epiphyseal plate. Another reason appears to be a qualitative change such as the
      variety of the fracture patterns and an increase in the collagen network density
      of the cartilaginous matrix with age.

PMID- 8283117
TI  - [An experimental study on the pathological changes of the intervertebral disc and
      its surrounding tissues after intradiscal injection of various chemical
      substances (the first report)].
AB  - The author has investigated the possible clinical application of new suitable and
      reliable substances for intradiscal therapy. MATERIALS AND METHODS; Several
      concentrations of various chemical substances (HCl, NaOH, etc.) were injected
      into the lumbar intervertebral discs of 165 Japanese white rabbits. These animals
      were sacrificed periodically and the obtained disc specimens were submitted to
      histological examinations with light and electron microscopes. Effects of these
      substances on the dura mater and the spinal cord of 87 guinea pigs were also
      investigated histologically. RESULTS; Acids, bases and ethanol, especially in
      high concentration, caused intense necrosis of nucleus pulposus cells and
      degeneration of the matrix as well as destruction of the annulus fibrosus
      occasionally with necrosis of endplate cells. Narrowing of disc height was
      frequently observed. Hemorrhage and inflammatory changes of surrounding tissues
      including the dura mater and the spinal cord were not rare. While low
      concentration acids and bases as well as other chemical substances such as osmic
      acid and phenol showed somewhat confined changes to the nucleus pulposus with
      minimal changes to peridiscal tissues including the neural structures. In other
      words, changes induced by these chemical substances were circumscribed to the
      nucleus pulposus, provided the concentration of the substances were adjusted to
      an appropriate level. DISCUSSIONS; Recently, chemonucleolysis and percutaneous
      discectomy have been recognized as alternatives to surgical treatments for lumbar
      disc herniation and seemed to have established a new concept "intermediate
      therapy". However, each method has certain disadvantages as well. The purpose of
      the present study is to find out safer and reliable agents that can dissolve the
      nucleus pulposus without adverse side effects such as anaphylaxis or transverse
      myelitis that occurs with some nucleolytic enzymes. In this perspective, the
      results of this study have provided evidences that certain chemical substances
      have possible clinical application in intradiscal therapy.

PMID- 8283118
TI  - [The effect of total en bloc spondylectomy on spinal cord circulation].
AB  - The physiologic and morphologic effects of total en bloc spondylectomy (TES) on
      spinal cord circulation in cats were studied by spinal cord blood flow (SCBF) and
      examined with microangiogram and scanning corrosion casts. SCBF decreased
      significantly following laminectomy (average 22.1%), while circumspinal
      decompression produced no further decrease. Ligation of the Adamkiewicz artery
      decreased SCBF only by 19.0% in average and caused no conduction disturbance
      electrophysiologically. TES on the vertebra at the level of the Adamkiewicz
      artery produced no morphologic changes in spinal cord vessels and self-regulation
      of blood flow was also preserved. These findings indicate that total en bloc
      spondylectomy on one vertebra has little effect on spinal cord circulation.

PMID- 8283119
TI  - [Metabolic bone disease].

PMID- 8283120
TI  - [The radiographical changes with age of the treated clubfoot].
AB  - One hundred and eighteen feet out of 83 cases of congenital clubfoot treated
      mainly by early posterior release were examined for changes with age in
      radiographical measurements. They were classified into three groups according to
      treatment courses. Group I is the cases treated conservatively, group II is the
      cases which received early posterior release and group III is the cases that
      needed other operations or treatment courses. In all groups, talo-calcaneal index
      (TC index) decreased and calcaneal pitch (CP) increased with age but no
      remarkable change occurred in talo-1st-metatarsal angle (TMA). Though the
      patterns of changes of all measurements in each group were similar to those of
      controls, the values were lower than controls' except CP. In TC index, the
      difference between controls and group II was about 20 degrees at each age. The
      mean TC index of group III was always the lowest in all groups. The mean TMA
      value differed about 10 to 15 degrees from those of controls in group I and II,
      and about 20 degrees in group III constantly till twelve years of age. The values
      of CP approached the controls' values gradually with age in all treatment groups.
      In order to maintain good radiographical findings, the values of TC index and TMA
      should be approached to those of control group after serial casts of initial
      treatment.

PMID- 8283121
TI  - Comment on Rosenberg et al. (1993)

PMID- 8283122
TI  - Response to Rovet et al.

PMID- 8283123
TI  - Brain basis for dyslexia: a summary of work in progress.
AB  - Studies of brain/behavior relations in the last decade have converged to suggest
      a left-hemisphere functional deficit for dyslexia. The relationship is most
      convincing at the microscopic level, where anomalous neural organization has been
      associated with reading, and at the macroscopic level, where several studies find
      atypical hemispheric symmetry in the language-related temporal region in
      individuals with dyslexia. Physiological studies measuring brain function during
      cognitive challenge have now begun to accumulate in support of a left-hemisphere
      deficit in dyslexia. This article summarizes work in progress on the structure
      and physiological profiles of reading disability and relates the findings to core
      left-hemisphere language functions.

PMID- 8283124
TI  - Effects of instruction on the decoding skills of children with phonological
      processing problems.
AB  - This article reviews research carried out by the Bowman Gray Learning
      Disabilities Project concerning the role of instruction in the acquisition of
      word-identification (decoding) skills in children at risk for reading
      disabilities. A group of 81 kindergarten children were identified as at risk for
      reading disabilities based on teacher assessment and weak or deficient
      phonological-processing skills. These children were classified as to type of
      phonological-processing problem (i.e., phonological awareness or retrieval of
      phonological information) and were randomly assigned to either a Code or Context
      instructional method for first and second grades. Children who received Code
      instruction scored higher than children receiving context instruction on a
      variety of reading and spelling measures at the end of first and second grades.
      The elements of the Code instructional program considered critical to the success
      of a beginning reading instruction program for children with phonological
      processing problems are discussed.

PMID- 8283125
TI  - A mother's thoughts on inclusion.

PMID- 8283126
TI  - The Learning Disabilities Association of America.

PMID- 8283127
TI  - Position paper on full inclusion of all students with learning disabilities in
      the regular education classroom. Learning Disabilities Association of America.

PMID- 8283128
TI  - Concerns about the full inclusion of students with learning disabilities in
      regular education classrooms. Council for Learning Disabilities.

PMID- 8283129
TI  - A reaction to full inclusion: a reaffirmation of the right of students with
      learning disabilities to a continuum of services. The National Joint Committee on
      Learning Disabilities.

PMID- 8283130
TI  - Phonological processes, confrontational naming, and immediate memory in dyslexia.
AB  - A group of poor readers classified as dyslexic by age/IQ discrepancy criteria (n
      = 42) were contrasted with two clinic control groups: 56 adequate-for-age readers
      with attention deficit disorder (ADD) and 21 poor-for-age readers not meeting the
      IQ discrepancy criterion (slow/borderline group). The children (33 girls, 86
      boys) ranged in age from 7.5 years to 12 years. Variables chosen for study
      included simple and complex phonological processing, speech rate, continuous
      naming speed, running memory span, serial memory span, and mental addition.
      Evidence is presented that the two poor reader groups are distinguishable. Unlike
      the dyslexic group, the slow/borderline group did not differ from the ADD group
      on three key measures: simple auditory phonological sensitivity, continuous
      naming speed, and running memory span. Stepwise regression to predict word list
      reading level showed that once age and verbal IQ were removed (51% of variance),
      these three key measures accounted for an additional 22% of the variance (R =
      0.86, R2 = 0.73). The single best predictor of word list reading level was
      nonsense word list reading level, which was explained by the same set of five
      variables that explained real word reading (R = 0.77, R2 = .60). Severity of
      attentional problems was not linearly related to reading skill in this clinic
      sample.

PMID- 8283131
TI  - Cognitive abilities of children at 7 and 12 years of age in the Colorado adoption
      project.
AB  - To test the hypothesis that adopted children are at an elevated risk for learning
      disabilities, the achievement and WISC-R test scores of a nonclinical sample of
      adopted and nonadopted (control) children were compared at 7 years of age (n =
      108 adopted males, 91 adopted females, 116 control males, 100 control females)
      and 12 years of age (n = 69 adopted males, 61 adopted females, 56 control males,
      44 control females). Although the average Verbal IQ of the adopted children was
      significantly lower than that of the nonadopted children at both ages, these
      differences accounted for only about 2% to 4% of the variance. When scores on the
      individual subtests of the WISC-R were compared, the group difference was
      significant only for Similarities at age 7, and for Comprehension at age 12.
      Moreover, with regard to the achievement tests, the proportion of adopted
      children who scored more than 1.5 standard deviations below expected, based on
      IQ, was not significantly greater than that of controls. Also, the proportions of
      adopted and control children placed in special education classes were not
      significantly different. Thus, the results of this study provide little or no
      evidence for an increased risk of learning disabilities in "easily placed"
      adopted children.

PMID- 8283132
TI  - Adolescents with learning disabilities: a comparative life-stream interpretation.
AB  - The subjective experiences of adolescents with learning disabilities (LD) were
      compared to those of their low-achieving and normally achieving peers. Three
      groups of juniors and seniors from one suburban high school district, 18 students
      with learning disabilities (15 males, 3 females), 17 low-achieving students (12
      males, 5 females), and 20 average-achieving students (12 males, 8 females), were
      given electronic pagers and booklets for 1 week. They were signaled every 40
      minutes during school hours, and every 2 hours after school. As soon as possible
      after receiving a signal, they responded to questions in their booklets. The
      questions provided subjective measures on levels of affect, activation, cognitive
      efficiency self-esteem, motivation, and feedback from others. The students with
      learning disabilities reported feeling more positive and active than either of
      the other groups during school hours, while after school there were no
      differences on any of the subjective measures for the three groups. Specific LD
      school practices are high-lighted for their probable impact on the heightened
      affect and activation of the students with learning disabilities.

PMID- 8283133
TI  - Inducing adaptive coping self-statements in children with learning disabilities
      through self-instruction training.
AB  - This study investigated the efficacy of a coping strategy in reducing math
      anxiety in children with learning disabilities (LD). The coping strategy was
      based on cognitive behavior modification (CBM). Twenty children from Grades 4 to
      7 participated in the study. Half of them were children with LD and the remaining
      were normally achieving children. The dependent measures were self-talk data and
      performance data on math (fraction) problems. Pretest data indicated that
      normally achieving children produced substantially more positive self-talk than
      children with learning disabilities. Subsequent to training in the use of the CBM
      based coping strategy, children with LD produced a comparable amount of positive
      self-talk at posttest as found in normally achieving children. Moreover, there
      was a moderate, positive correlation between increased positive self-talk and
      math performance among the children with LD. The results clearly indicated that
      the children with LD had learned to cope with their math anxiety via a CBM-based
      strategy. More generally, the results of the study suggest that CBM strategies
      can be effectively applied to the affective domain. This broader implication and
      the limitations of the study are discussed.

PMID- 8283134
TI  - Complement and tumor necrosis factor-alpha contribute to Mac-1 (CD11b/CD18) up
      regulation and systemic neutrophil activation during endotoxemia in vivo.
AB  - The increased expression of Mac-1 (CD11b/CD18) adhesion glycoproteins on
      neutrophils was studied using flow cytometry in male Fischer 344 rats treated
      with 5 mg/kg Salmonella enteritidis endotoxin. A rapid and sustained threefold
      increase of Mac-1 expression was observed after endotoxin injection. Inhibition
      of complement activation with the soluble complement receptor type 1 (sCR1)
      completely suppressed the initial up-regulation of Mac-1 (< or = 15 min) but did
      not prevent the activation during the later phase (30-90 min). During that time
      period, Mac-1 expression increased in parallel with the concentration of tumor
      necrosis factor alpha (TNF-alpha) in plasma and could be significantly attenuated
      with TNF antiserum. To verify the results, isolated human neutrophils were
      incubated with rat plasma obtained at various times after endotoxin injection.
      Using shape change as indicator of neutrophil activation, complement and TNF
      alpha could be identified as responsible mediators for neutrophil activation
      during endotoxemia in vivo. In contrast, the massive neutrophil accumulation in
      the liver after endotoxin was only slightly reduced by sCR1 and unaffected by TNF
      antiserum. It is concluded that Mac-1 up-regulation on neutrophils after
      endotoxin injection in vivo may have limited relevance for hepatic neutrophil
      infiltration but may be important for the pathogenesis of endotoxin-induced liver
      injury by facilitating adherence-dependent neutrophil cytotoxicity.

PMID- 8283135
TI  - Inhibition of crystal-induced neutrophil activation by a protein tyrosine kinase
      inhibitor.
AB  - The objective of this work was to investigate the role of tyrosine kinase in
      monosodium urate monohydrate (MSUM) and calcium pyrophosphate dihydrate (CPPD)
      crystal-induced neutrophil activation using the tyrosine kinase inhibitor
      lavendustin C (LVC). Human neutrophils pretreated with LVC at concentrations
      between 10 and 150 microM or control neutrophils were stimulated by plasma-coated
      CPPD or uncoated MSUM, and chemiluminescence, superoxide generation,
      intracellular calcium concentration, and degranulation (myeloperoxidase and
      lysozyme release) were monitored with time. LVC strongly inhibited
      chemiluminescence, superoxide anion generation, myeloperoxidase and lysozyme
      release, and calcium mobilization. After 1-min crystal-neutrophil incubations,
      neutrophil cytosolic fractions showed extensive inhibition of tyrosine kinase
      activity by LVC. We conclude that the inhibition of neutrophil responses to
      crystal stimulation, by the protein tyrosine kinase inhibitor LVC, provides
      evidence that supports the involvement of tyrosine kinases in crystal-induced
      neutrophil activation.

PMID- 8283136
TI  - Monocyte chemoattractant protein 1 (MCP-1) expression occurs in toxic rat liver
      injury and human liver disease.
AB  - Considerable evidence suggests that monocytes/macrophages play a crucial role in
      the process of liver injury and repair. Recent investigations have focused on the
      function of various macrophage-produced cytokines in liver disease. Much is still
      unknown, however, about the mechanism of macrophage recruitment and activation
      during liver disease. To further define this process, the gene expression of the
      monocyte chemoattractant monocyte chemoattractant protein 1 (MCP-1) was examined
      in animal and human liver disease. MCP-1 mRNA was not found in normal rat liver
      by Northern blot analysis. After single-dose treatments with the hepatotoxins
      carbon tetrachloride and galactosamine, MCP-1 mRNA was detectable beginning at 2
      and 4 h after treatment, respectively, and was expressed continuously until 60-72
      h. During chronic carbon tetrachloride administration, MCP-1 mRNA levels were
      elevated for the entire 10 weeks of treatment with peak levels of expression
      occurring early (weeks 1-3) and late (weeks 8-10) in this model. Isolated liver
      cell fractions from rats treated for 3 weeks with carbon tetrachloride revealed
      the major cellular source of MCP-1 mRNA to be fat-storing or Ito cells, with some
      expression occurring in the endothelial cell fraction. Studies of potential
      inducers of hepatic MCP-1 expression showed that lipopolysaccharide, tumor
      necrosis factor-alpha, and interleukin-1 alpha and beta treatments all led to MCP
      1 expression. Finally, studies of human liver samples revealed MCP-1 gene
      expression in nondiseased liver and greatly increased levels in livers from
      patients with fulminant hepatic failure. These data implicate MCP-1 from fat
      storing cells as a modulator of the process of liver injury and further support a
      role for MCP-1 in the pathogenesis of human disease.

PMID- 8283137
TI  - Ligation of N-acetylgalactosamine-containing structures on rat bone marrow cells
      enhances myeloid differentiation and murine granulocyte-macrophage colony
      stimulating factor-induced proliferation.
AB  - Previously we have reported the differentiation-dependent expression of a soybean
      agglutinin (SBA)-binding structure on rat bone marrow cells (BMCs) during their
      differentiation into macrophages (m phi s). In the present study we tried to
      analyze the functional role of the SBA-binding structure in BMC proliferation and
      differentiation. Addition of SBA to BMC cultures driven into m phi
      differentiation by recombinant murine granulocyte-macrophage colony-stimulating
      factor (rmGM-CSF), resulted in a two- to threefold increased proliferation rate
      compared with rmGM-CSF alone. However, the number of colonies in methyl cellulose
      was not increased by SBA. The effect of SBA was dose dependent (from 4 to 83 pM
      SBA), with a maximum effect at 83 pM. Experiments to detect a possible
      synergistic effect of additional cytokines produced by BMC after SBA treatment
      were inconclusive. The enhancing effect of SBA was also seen when high-density
      cells, which did not proliferate in response to rmGM-CSF (mainly granulocytes),
      were removed. Therefore, SBA may increase the CSF reactivity of responsive m phi
      progenitor cells directly by binding to N-acetylgalactosamine residues on their
      surface.

PMID- 8283138
TI  - Effect of glycyrrhizin, cyclosporin A, and tumor necrosis factor alpha on
      infection of U-937 and MRC-5 cells by human cytomegalovirus.
AB  - Reactivation of latent or persistent human cytomegalovirus (HCMV) infection of
      monocytes or macrophages occurs under immunosuppressive conditions. We
      investigated the effect of glycyrrhizin (GL), cyclosporin A (CsA), and tumor
      necrosis factor-alpha (TNF-alpha) on the viral DNA synthesis and antigen
      expression of HCMV in U-937 and MRC-5 cells. Although GL inhibited the viral
      antigen expression of HCMV in human monocytic cell line U-937 and human embryonic
      lung cell line MRC-5 in the study, as determined by flow cytometry and
      immunofluorescence assay, immediate early HCMV DNA was detected by the polymerase
      chain reaction. CsA or TNF had no inhibitory effect on HCMV in U-937 or MRC-5
      cells. The HCMV infection model with U-937 or MRC-5 cells is of use for
      clarifying not only the mechanism of persistent infection but also the anti-HCMV
      effect of chemical agents.

PMID- 8283139
TI  - Hyperimmune serum modulates allergic response to spores in a murine model of
      allergic aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a disease in atopic asthmatics
      characterized by eosinophilia and elevated levels of immunoglobulin E (IgE) and
      IgG antibodies to the ubiquitous fungus Aspergillus fumigatus (Af). The role of
      specific antibodies in the disease process is not clear. In this study, BALB/c
      mice were injected with hyperimmune serum from syngeneic mice exposed to soluble
      antigen of Af. These mice were then exposed to either Af spores or soluble
      antigen. Total IgE, Af-specific IgG1 (enzyme-linked immunosorbent assay) in
      serum, and eosinophils (eosinophil peroxidase assay) in lungs and bone marrow
      were measured. Histologic sections of lungs were examined for cellular
      infiltration and morphologic changes. Results indicate a suppression of increase
      in levels of antibodies and eosinophilia in mice receiving immune serum and
      exposed to spores compared with controls receiving phosphate-buffered saline
      treatment. Spores being the primary source of exposure to Af in ABPA, these
      results are significant in understanding the role of preexisting specific
      antibodies in patients.

PMID- 8283140
TI  - Processing and intracellular transport of cathepsin G and neutrophil elastase in
      the leukemic myeloid cell line U-937-modulation by brefeldin A, ammonium
      chloride, and monensin.
AB  - The effects of brefeldin A, monensin, and the weak base NH4Cl on the biosynthesis
      and processing of cathepsin G and neutrophil elastase of myeloid cells were
      investigated. Monoblast-like U-937 cells were biosynthetically labeled with
      [35S]methionine, followed by subcellular fractionation, immunoprecipitation, and
      analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      fluorography. Brefeldin A inhibited proteolytic processing, intracellular
      transport, and secretion. The effects were reversible inasmuch as removal of
      brefeldin A resulted in a normal pattern of processing and transfer to high
      density organelles, corresponding to lysosomes, and restitution of constitutive
      secretion of precursor forms. Both cathepsin G and neutrophil elastase acquired
      resistance to endoglycosidase-H, suggesting that conversion to complex
      oligosaccharide side chains also occurs in the presence of brefeldin A. Monensin
      and NH4Cl inhibited final proteolytic processing, indicating either that
      acidification is necessary for directing cathepsin G and neutrophil elastase to
      lysosomal-like organelles or that the protease(s) responsible for processing
      requires an acid pH. We conclude that pH-dependent proteolytic processing of
      cathepsin G and neutrophil elastase occurs in post-Golgi structures and that
      transfer to lysosomes or an immediately prelysosomal compartment is mandatory for
      complete processing.

PMID- 8283141
TI  - Activation of NF-kappa B may be necessary but is not sufficient for induction of
      H-2 antigens by TNF in J558L murine myeloma cells.
AB  - We have investigated the role of the transcription factor NF-kappa B in the
      induction of H-2 antigens by tumor necrosis factor (TNF) in murine J558L myeloma
      cells. An earlier report suggested that J558L cells may have a defect in NF-kappa
      B activation in response to some stimuli. Treatment of J558L cells with either
      TNF or lipopolysaccharide (LPS) resulted in nuclear translocation of NF-kappa B,
      as demonstrated by electrophoretic mobility shift assay. Both TNF and LPS
      activated the same NF-kappa B nuclear complexes, composed of the p50 and p65
      subunits. LPS mediated a stronger and more sustained activation of NF-kappa B
      than TNF. In contrast, TNF induced higher levels of H-2 antigen surface
      expression than did LPS, suggesting that activation of NF-kappa B is not
      sufficient for optimal enhancement of H-2 expression. An inhibitor of NF-kappa B
      activation, pyrrolidinedithiocarbamate (PDTC), dramatically reduced the induction
      of H-2 antigen by TNF, supporting the view that NF-kappa B is required for TNF
      induced H-2 antigen expression. Constitutive levels of H-2 antigen expression on
      the cell surface and of nuclear NF-kappa B also decreased after PDTC treatment.
      However, PDTC had a smaller inhibitory effect on LPS-induced NF-kappa B
      activation and H-2 antigen expression, suggesting that TNF and LPS activate NF
      kappa B by somewhat different pathways.

PMID- 8283142
TI  - Distinct patterns of differentiation induced in the monocytic cell line Mono Mac
      6.
AB  - The human Mono Mac 6 cell line exhibits many characteristics of mature blood
      monocytes including expression of the CD14 molecule and production of cytokines,
      such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor. To determine
      whether these cells can be further differentiated, we treated the cells for up to
      3 days with either prostaglandin E2 (PGE2; 10(-5) or 10(-6) M),
      lipopolysaccharide (LPS; 10-20 ng/ml), or tetradecanoylphorbol-13-acetate (TPA;
      10-50 ng/ml). All three reagents reduced proliferation and expression of the
      early myelomonocytic antigen CD33, and all increased phagocytosis of
      staphylococci and constitutive expression of mRNA for the macrophage colony
      stimulating factor (M-CSF) receptor. By contrast, with respect to CD23 (Fc
      epsilon RII) expression, CD14 expression, and production of O2-, the three
      reagents induced distinct responses. Expression of CD23 (Fc epsilon RII) on Mono
      Mac 6 cells (36%) was not increased by LPS and TPA but was increased by PGE2
      treatment to 48%, with a 50% increase of fluorescence intensity. The CD14
      antibody My4 stained more than 75% of untreated Mono Mac 6 cells with a specific
      mean fluorescence intensity of 87.5 channels. This staining was increased more
      than twofold by both PGE2 and LPS. Staining with the CD14 antibody UCHM1 (6%) was
      increased to 43% by PGE2 and to 43% by LPS. This increase in CD14 cell surface
      expression was accompanied by a rise in soluble CD14 and enhancement of CD14
      mRNA. By contrast, TPA treatment resulted in a twofold decrease of CD14 cell
      surface staining with no significant change in sCD14, while CD14 mRNA was
      transiently down-regulated. Secretion of O2- (stimulated by TPA) was already
      detectable in untreated Mono Mac 6 cells (6.1 mmol/10(6) cells/30 min), and this
      response was enhanced 10-fold by pretreatment with LPS but not with PGE2 or TPA.
      The kinetics of M-CSF receptor mRNA, CD14 expression, and O2- production revealed
      that these monocytic features started to increase at 6-24 h and were maximal at 2
      days. These data suggest that the three reagents induce maturation of the Mono
      Mac 6 cells to different levels or into different branches of the monocyte system
      with the notable differences that PGE2 enhances CD23 expression, LPS enhances O2-
      secretion, and TPA down-regulates CD14.

PMID- 8283143
TI  - Interleukin-2 suppresses activated macrophage intracellular killing activity by
      inducing macrophages to secrete TGF-beta.
AB  - Phorbol myristate acetate (PMA) treatment of an EL-4 thymoma cell line (EL
      4FARRAR) induced secretion of a factor that inhibited intracellular killing of
      Leishmania major amastigotes by activated macrophages. Analysis of the cytokines
      produced by EL-4 cells after PMA stimulation identified interleukin-2 (IL-2, 2500
      U/ml), IL-4 (1280 U/ml), interferon-gamma (IFN-gamma; 100 U/ml), and granulocyte
      macrophage colony-stimulating factor (GM-CSF; 50 U/ml). Neither tumor necrosis
      factor nor transforming growth factor beta (TGF-beta) was detected. Each of the
      cytokines present in EL-4 fluids was assessed for capacity to activate
      macrophages for destruction of parasites or to suppress intracellular killing.
      IFN-gamma and GM-CSF both activated macrophages to kill Leishmania; IL-2 and IL-4
      had no activity for induction of this antimicrobial effector function. IL-2 and
      IL-4 were tested for their capacity to inhibit lymphokine- or IFN-gamma-induced
      destruction of L. major by macrophages: IL-4 was ineffective, but IL-2 markedly
      suppressed the activation of macrophages for intracellular killing. Addition of >
      or = 10 U/ml of IL-2 at the time of infection, or up to 4 h before, blocked up to
      100% of the capacity of activated macrophages to kill intracellular amastigotes.
      Immunoaffinity treatment of EL-4 fluids with anti-IL-2 antibody resulted in > 80%
      reduction in suppression of intracellular killing. The suppressive effects of IL
      2 were not direct, but mediated by TGF-beta. IL-2 induced resident peritoneal
      macrophages to secrete > 5000 pg/ml TGF-beta 1, a quantity that is > 500-fold
      higher than constitutive background levels (20-40 pg/ml) and is sufficient to
      block intracellular killing activities. This increase in secretion of TGF-beta
      was not dependent increases in TGF-beta 1 mRNA. Treatment of cultures with EL-4
      fluids or recombinant IL-2 in the presence of antibody to TGF-beta 1 blocked the
      suppressive activity of both. Thus, IL-2 was the major suppressor factor in EL-4
      fluids, and it acted indirectly through the induction and autocrine action of TGF
      beta.

PMID- 8283144
TI  - Leishmania donovani infection enhances macrophage viability in the absence of
      exogenous growth factor.
AB  - Bone marrow-derived macrophages rapidly die in the absence of macrophage growth
      factor (M-CSF). However, as demonstrated here, bone marrow-derived macrophages
      infected with Leishmania donovani exhibit increased viability in the absence of
      exogenous growth factor. Forty-eight hours after inoculation with promastigotes
      or amastigotes, infected cell cultures contained 180 and 95% more cells,
      respectively, than control cultures. This effect was specific to Leishmania
      infection, as uptake of latex beads or avirulent promastigotes by macrophages did
      not enhance cell viability. L. donovani-infected macrophages also displayed
      increased phagocytic capacity, as compared with control macrophages and
      macrophages grown continuously in M-CSF-containing medium. Supernatants collected
      from infected cells elaborated a factor(s) that enhanced macrophage viability but
      did not stimulate macrophage DNA synthesis. This activity of L. donovani-infected
      cell-conditioned medium could be abrogated by preincubation of macrophages with
      cycloheximide before inoculation with the parasite, implying that macrophage
      protein synthesis is required for the elaboration of this factor(s).

PMID- 8283145
TI  - Endocytosis of sulfatides by macrophages: relationship to the cellular uptake of
      phosphatidylserine.
AB  - These studies initially examined the effect of sulfatides on the endocytosis of
      phosphatidylserine (PS) liposomes in J774 macrophages employing liposomes
      composed entirely of PS and the nonexchangeable radiolabel [3H]cholesteryl
      hexadecyl ether. Bovine brain sulfatides significantly inhibited the uptake of PS
      liposomes by macrophages to a level of approximately 15% of control values. To
      examine whether macrophages were also capable of recognizing and internalizing
      sulfatides, sulfatide-containing liposomes were prepared using
      phosphatidylcholine (PC), cholesterol, and sulfatides (6:2:4 molar ratio)
      incorporating the same radiolabel. The sulfatide-containing liposomes were found
      to be avidly endocytosed by macrophages. Uptake of the sulfatide-containing
      liposomes by macrophages was significantly greater than the uptake of liposomes
      made without sulfatides. When the macrophages were incubated with the anionic
      compounds dextran sulfate and fucoidin, both the binding of the liposomes to the
      macrophages at 4 degrees C and the internalization of the liposomes at 37 degrees
      C were inhibited to approximately 10% of control values. The negatively charged
      phospholipids phosphatidylglycerol and cardiolipin significantly inhibited the
      uptake of sulfatide-containing liposomes, and PS was not effective in reducing
      the cellular uptake of these liposomes. Both oxidized low-density lipoprotein
      (LDL) and acetylated LDL reduced the uptake of the sulfatide-containing
      liposomes; the uptake observed in the presence of acetylated LDL and oxidized LDL
      was approximately 70% and 40%, respectively, of control values. These findings
      demonstrate that macrophages can efficiently endocytose both sulfatides and
      negatively charged phospholipids to remove them from the circulation.

PMID- 8283146
TI  - Signal-detection properties of verbal self-reports.
AB  - The bias (B'H) and discriminability (A') of college students' self-reports about
      choices made in a delayed identity matching-to-sample task were studied as a
      function of characteristics of the response about which they reported. Each
      matching-to-sample trial consisted of two, three, or four simultaneously
      presented sample stimuli, a 1-s retention interval, and two, three, or four
      comparison stimuli. One sample stimulus was always reproduced among the
      comparisons, and choice of the matching comparison in less than 800 ms produced
      points worth chances in a drawing for money. After each choice, subjects pressed
      either a "yes" or a "no" button to answer a computer-generated query about
      whether the choice met the point contingency. The number of sample and comparison
      stimuli was manipulated across experimental conditions. Rates of successful
      matching-to-sample choices were negatively correlated with the number of matching
      to-sample stimuli, regardless of whether samples or comparisons were manipulated.
      As in previous studies, subjects exhibited a pronounced bias for reporting
      successful responses. Self-report bias tended to become less pronounced as
      matching-to-sample success became less frequent, an outcome consistent with
      signal-frequency effects in psychophysical research. The bias was also resistant
      to change, suggesting influences other than signal frequency that remain to be
      identified. Self-report discriminability tended to decrease with the number of
      sample stimuli and increase with the number of comparison stimuli, an effect not
      attributable to differential effects of the two manipulations on matching-to
      sample performance. Overall, bias and discriminability indices revealed effects
      that were not evident in self-report accuracy scores. The results indicate that
      analyses based on signal-detection theory can improve the description of
      correspondence between self-reports and their referents and thus contribute to
      the identification of environmental sources of control over verbal self-reports.

PMID- 8283148
TI  - The behavioral economics of production.
AB  - In two experiments, thirsty rats licked an empty spout instrumentally for water
      delivered at a neighboring spout. Each such pair of spouts constituted a work
      station, and one, two, or three stations were available in the test enclosure. In
      1-hr sessions, the rats worked alone or in the company of 1 or 2 other rats, and
      performed either five, 10, or 40 licks at the empty spout for each water
      delivery. The total number of empty-spout licks, summed across rats and stations,
      increased with the empty-lick requirement and, with some exceptions, the number
      of rats in the enclosure and the number of work stations available. A Cobb
      Douglas production function, with instrumental responding as an output and the
      three independent variables as inputs, accounted for a significant percentage of
      the variance. Contrary to that function, output failed to increase with
      additional rats (or work stations) when the number of work stations (or rats) was
      relatively small.

PMID- 8283147
TI  - A parametric variation of delayed reinforcement in infants.
AB  - This study is an exploration of the parameters of delayed reinforcement with 6
      infants (2 to 6 months old) in two experiments using single-subject repeated
      reversal designs. In Experiment 1, unsignaled 3-s delayed reinforcement was used
      to increase infant vocalization rate when compared to a differential
      reinforcement-of-other-than-vocalization condition and a yoked, no-contingency
      comparison condition. In Experiment 2, unsignaled 5-s delayed reinforcement was
      used to increase infant vocalization rate when compared to an alternating
      treatments comparison condition. The alternating-treatments comparison consisted
      of 3-min components of differential reinforcement of other behavior and 3-min
      components of a nontreatment baseline. Successful conditioning was obtained in
      both experiments. These results contrast with those of previous infancy
      researchers who did not obtained conditioning with delays of 3 s and who
      attributed their findings to the limitations of the infant's memory capacity. We
      present an alternative conceptual framework and methodology for the analysis of
      delayed reinforcement in infants.

PMID- 8283149
TI  - Conditional discrimination in mentally retarded subjects: programming acquisition
      and learning set.
AB  - In Experiment 1, 3 subjects with retardation were exposed to two visual-visual
      arbitrary matching-to-sample problems each day. One conditional discrimination
      was presented under trial-and-error conditions, and the other was presented under
      a component training procedure. The latter began by establishing the comparison
      discrimination and its rapid reversal. The successive discrimination between the
      sample stimuli was established through differential naming. Then, sample naming
      was maintained in conditional discrimination sessions in which the same sample
      was presented in blocks of consecutive trials. Block size was decreased across
      sessions until sample presentation was randomized as in trial-and-error training
      (but with naming maintained). Two subjects initially learned only with component
      training. The performance of the 3rd subject was inconsistent across conditional
      discriminations. One of the successful subjects ultimately learned rapidly and
      consistently with trial-and-error procedures. Experiment 2 sought to demonstrate
      learning set in the other 2 subjects. Elements of the component training
      procedure were withdrawn over successive conditional discriminations. Ultimately,
      1 subject nearly always learned under trial-and-error conditions, and the other
      learned under trial-and-error conditions combined with differential sample
      naming.

PMID- 8283150
TI  - A quantitative analysis of sensitivity to the conditioned reinforcing value of
      terminal-link stimuli in a concurrent-chains schedule.
AB  - Pigeons were exposed to a concurrent-chains schedule in which a single variable
      interval 30-s schedule was used in the initial links and fixed-time schedules
      were used in the terminal links. Three types of keylight conditions were used in
      the terminal links. In the first condition, different delays were associated with
      different keylight stimuli (cued condition). In the second condition, different
      delays were associated with the same stimulus, either a blackout (uncued blackout
      condition) or a white key (uncued white condition). Paired values of terminal
      link fixed-time schedules differed by a constant ratio of 3:1, while the absolute
      value of delays was varied from 3 s to 54 s. The results showed that choice
      proportions for the shorter of two delays increased when the absolute size of the
      delays was increased for all keylight conditions. Further, the choice proportions
      for the shorter delay increased from the uncued blackout condition, to the uncued
      white condition, to the cued condition. A modified version of Fantino's (1969)
      delay-reduction model (expressed as a function relating the response ratio to the
      delay-reduction ratio) can be applied to these data by showing that sensitivity
      to delay reduction increased from the uncued blackout condition, to the uncued
      white condition, to the cued condition. Thus, the present study demonstrated that
      a modified version of the delay-reduction model can be used to assess
      quantitative differences in the terminal-link keylight condition in terms of
      sensitivity to delay reduction (i.e., the conditioned reinforcing value of the
      terminal-link keylight stimuli).

PMID- 8283151
TI  - The effect of increased response requirements on discriminative performance of
      the domestic hen in a visual acuity task.
AB  - Six domestic hens were trained in a spatial discrimination task. A controlled
      reinforcement procedure insured that the ratio of scheduled and obtained
      reinforcement remained equal. Gray stimuli and gratings ranging in spatial
      frequency from 1 to 10 cycles per millimeter were presented in seven descending
      series of probes. The response requirement to the sample key was varied from
      fixed ratio 1 to fixed ratio 40 in seven experimental conditions. An increase in
      response requirements from fixed ratio 1 to fixed ratio 5 and fixed ratio 10
      resulted in significantly higher accuracy at discriminable grating values.
      Further increases in response requirements did not consistently improve
      performance. Generally, response biases increased and occasionally became extreme
      for probes at finer gratings with increased response requirements.

PMID- 8283152
TI  - Schedule-induced defecation by rats during ratio and interval schedules of food
      reinforcement.
AB  - Lever pressing in rats was maintained by continuous and intermittent schedules of
      food while defecation was monitored. In Experiment 1, reinforcement densities
      were matched across variable-ratio and variable-interval schedules for three
      pairs of rats. Defecation occurred in all 3 rats on the variable-ratio schedule
      and in all 3 rats on the yoked variable-interval schedule. In Experiment 2, fixed
      ratio and fixed-interval schedules with similar reinforcement densities
      maintained lever pressing. Defecation occurred in 3 of 4 rats on the fixed-ratio
      schedule and in 4 of 4 rats on the fixed-interval schedule. Almost no defecation
      occurred during continuous reinforcement in either experiment. These results
      demonstrate that defecation may occur during both ratio and interval schedules
      and that the inter-reinforcement interval is more important than the behavioral
      requirements of the schedule in generating schedule-induced defecation.

PMID- 8283153
TI  - Responding changes systematically within sessions during conditioning procedures.
AB  - When the procedure is held constant within an experimental session, responding
      often changes systematically within that session. Many of these within-session
      changes in responding cannot be dismissed as learning curves or by-products of
      satiation. They have been observed in studies of positive reinforcement,
      avoidance, punishment, extinction, discrimination, delayed matching to sample,
      concept formation, maze and alley running, and laboratory analogues of foraging,
      as well as in the unconditioned substrates of conditioned behavior. When aversive
      stimuli are used, responding usually increases early in the session. When
      positive reinforcers are used, responding changes in a variety of ways, including
      increasing, decreasing, and bitonic functions. Both strong and minimal
      reinforcement procedures produce within-session decreases in positively
      reinforced behavior. Within-session changes in responding have substantial
      theoretical and methodological implications for research in conditioning.

PMID- 8283154
TI  - Unit price as a useful metric in analyzing effects of reinforcer magnitude.
AB  - In this paper, we applied the behavioral-economic concept of unit price to the
      study of reinforcer magnitude in an attempt to provide a consistent account of
      the effects of reinforcer magnitude on behavior. Recent research in the
      experimental analysis of behavior and in behavioral pharmacology suggests that
      reinforcer magnitude interacts with the schedule of reinforcement to determine
      response rate and total consumption. The utility of the unit-price concept thus
      stems from its ability to quantify this interaction as a cost-benefit ratio
      (i.e., unit price = characteristics of the schedule of reinforcement divided by
      magnitude of reinforcement). Research employing the unit-price concept has shown
      that as unit price increases, a positively decelerating function exists for
      consumption (i.e., a function with an increasingly negative slope, when plotted
      on log coordinates) and a bitonic function exists for response rate. Based on
      these findings, the present analysis applied the unit-price concept to those
      studies of reinforcer magnitude and drug self-administration that examined the
      effects of reinforcer magnitude on response rate using simple schedules of
      reinforcement (e.g., fixed-ratio schedule). This resulted in three findings: (a)
      Reinforcer-magnitude manipulations and schedule manipulations interact in a
      manner that can be quantified in terms of unit price as benefit and cost factors,
      respectively; (b) different reinforcer-magnitude manipulations are functionally
      interchangeable as benefit factors in the unit-price ratio; and (c) these
      conclusions appear warranted despite the differences in reinforcers (food or
      drug), species (dogs, monkeys, or rats), and schedules (interval or ratio), and
      despite the fact that these studies were not designed for a unit-price analysis.
      In methodological terms, these results provide further evidence that employing
      the unit-price concept is a parsimonious method for examining the effects of
      reinforcer magnitude. In theoretical terms, these results suggest that a single
      process may underlie the effect of combined reinforcer-magnitude and schedule
      manipulations.

PMID- 8283155
TI  - Two follow-up studies of preventive lipid-lowering trials support the validity of
      the lipid hypothesis.

PMID- 8283156
TI  - Mild hypertension: a summary of the 1993 World Health Organization/International
      Society of Hypertension (WHO/ISH) guidelines for the management of mild
      hypertension. Memorandum from a WHO/ISH meeting.

PMID- 8283157
TI  - The Helsinki Heart Study: an 8.5-year safety and mortality follow-up.
AB  - OBJECTIVES: Earlier monitoring of all symptoms, hospital admissions, cancer
      diagnoses and causes of death during gemfibrozil treatment had raised some
      suspicions which called for further follow-up. DESIGN: Close monitoring of
      selected, potentially adverse events amongst treated subjects after a placebo
      controlled trial and comparing occurrences to those in various untreated groups.
      SETTING: All participants of the Helsinki Heart Study (a controlled, 5-year,
      multi-clinic coronary heart disease (CHD) primary prevention trial with
      gemfibrozil and placebo) were offered gemfibrozil treatment and twice yearly
      follow-up for 3.5 years. Untreated groups in the source population and national
      cancer statistics were utilized in comparisons. SUBJECTS: Of the 2046
      dyslipidaemic men initially randomized to gemfibrozil, 2002 survivors entered the
      3.5-year follow-up; of the 2035 initial placebo men, 1992 continued to be
      monitored. INTERVENTIONS: Gemfibrozil was chosen for the follow-up by 66.3% of
      the gemfibrozil-treated and 68.5% of the placebo-treated men. MAIN OUTCOME
      MEASURES: Gastrointestinal symptoms, surgery, strokes, cancer incidence,
      mortality by cause. RESULTS: Gastrointestinal symptoms remained more common in
      the original gemfibrozil group. After 8.5 years strokes numbered 32 (gemfibrozil)
      vs. 37 (placebo), violent deaths 16 vs. 14, and cancers 51 in both groups. Total
      mortality was equal during the original 5 years, but higher in the gemfibrozil
      group post-trial, leading to an 8.5 year mortality of 101 vs. placebo 83 (P =
      0.19). This was mainly a result of higher cancer mortality in the gemfibrozil
      (30) than the placebo group (18, P = 0.08). An additional 18-month post-study
      registry follow-up disclosed 13 placebo and five gemfibrozil cancer deaths,
      altering the cancer mortality to gemfibrozil 35 vs. placebo 31 at 10 years.
      CONCLUSIONS: The most plausible explanation for the discrepancy between cancer
      incidence and cancer-specific mortality, based mainly on comparison with
      untreated groups, is delayed diagnosis. The increased cancer and total mortality
      is most probably due to chance, based on the later reversal of trends.

PMID- 8283158
TI  - The Helsinki Heart Study: coronary heart disease incidence during an extended
      follow-up.
AB  - OBJECTIVES: To confirm that coronary heart disease (CHD) can be prevented by
      gemfibrozil treatment and to estimate the long-term effect of the treatment.
      DESIGN: All participants of the Helsinki Heart Study, a controlled 5-year CHD
      primary prevention trial with gemfibrozil and placebo, were offered gemfibrozil
      treatment and biannual follow-up for 3.5 more years. SETTING: By the end of the
      multi-clinic double-blind trial, a 34% difference in definite cardiac events (56
      vs. 84; P < 0.2) had developed between the gemfibrozil and placebo groups.
      SUBJECTS: There were 2046 dyslipidaemic men in the gemfibrozil group at
      randomization, 1961 started the extended follow-up; the comparison group
      comprised 2035 men, and 5 years later 1928 men. INTERVENTIONS: Gemfibrozil was
      selected by 66.3% of gemfibrozil and 68.5% of placebo men without previous CHD
      end-points. MAIN OUTCOME MEASURES: Definite fatal and non-fatal CHD events are
      reported, possible CHD events were recorded but reported selectively. RESULTS:
      During the post-trial period the numbers of definite CHD events in both groups
      (54 vs. 47; NS) were smaller than expected without treatment, namely a reduction
      of around 40% for the original treatment groups. The mean incidence rates were in
      fact similar to that in the placebo group 5 years earlier. The post-trial CHD
      incidence was lowest amongst the placebo group men who later selected
      gemfibrozil. Cardiovascular mortality over the entire study period was similar
      but all-cause mortality was slightly higher amongst men of the original
      gemfibrozil group compared to the placebo group men (P = 0.19). CONCLUSIONS: Thus
      prolonged gemfibrozil treatment postpones cardiac events. This protective effect
      presumably involves both attenuation of atherosclerosis and mechanisms related to
      acute cardiac events.

PMID- 8283159
TI  - Light and biological rhythms.
AB  - Chronobiology--derived from chronos (time), bios (life), and logos (study of)--is
      the objective description of biological time structures and plays an important
      role in medicine. Circadian rhythms regulate the behaviour, physiology and
      function of living organisms at many biochemical levels. The influence of the
      rhythmic manifestation of life may be shown in the constructive effects of
      growth, development and maturation and is named anachronobiology. In contrast
      catachronobiology denotes deleterious effects of time and rhythm which may lead
      to a diseased state. This article summarizes some new data about light as a
      synchronizer of biological rhythms. A time-keeper--biological clock--is used by
      the body for readjustment of rhythms when this is desirable. More recently, light
      has been used to adjust the biological clock following changes of circadian
      rhythms during shift work or jet lag occurring when flying from one time zone to
      another. Light may be used to treat depression, sleep disorders, menstrual
      dysregulations and other illnesses with disturbed circadian and seasonal rhythms.
      Examples of the importance of chronopharmacology (time-dependent changes in drug
      metabolism and drug effect) are also presented. New findings indicate that
      circadian oscillators are under genetic control; a light-influenced regulatory
      role for cellular immediate-early genes in circadian behaviour has been
      discovered. This suggests that light is of importance in regulation of
      macromolecular synthesis at all levels of the circadian system.

PMID- 8283160
TI  - Hyperinsulinaemia, obesity, and syndrome X.
AB  - OBJECTIVE: The major aim of this study was to compare various aspects of
      carbohydrate, insulin, and lipoprotein metabolism, serum uric acid concentration,
      and blood pressure in normal subjects stratified on the basis of both plasma
      insulin concentration and degree of obesity. The hypothesis to be tested was that
      hyperinsulinaemia, per se, was associated with relative glucose intolerance,
      higher triglyceride and uric acid concentrations, lower high-density lipoprotein
      cholesterol concentration and higher blood pressure, irrespective of degree of
      obesity. DESIGN: This represents a case-control study, in which normal volunteers
      were subdivided into four equal groups based upon degree of obesity and plasma
      insulin response to a 74 g oral glucose challenge. SETTING: The study was
      performed in the out-patient clinic of a university hospital. SUBJECTS: Sixty
      four individuals were recruited for this study, subdivided into four groups based
      upon their plasma insulin concentration and body mass index. Subjects were
      classified as hyperinsulinaemic if their plasma insulin concentrations in
      response to an oral glucose challenge were more than two standard deviations
      above the mean of 732 volunteers previously studied [1]. Obesity was defined as a
      body mass index of > 30 kg m-2, and individuals were classified as non-obese if
      their body mass index was < 27.0 kg m-2. Based upon these criteria, four
      experimental groups were created: (i) non-obese hyperinsulinaemic (NOB hyper);
      (ii) obese hyperinsulinaemic (OB hyper); (iii) non-obese normoinsulinaemic (NOB
      normo); and (iv) obese normoinsulinaemic (OB normo). MAIN OUTCOME MEASURES:
      Subject groups were compared on the basis of the integrated plasma glucose
      response to a 75 g oral glucose challenge, fasting plasma triglyceride,
      cholesterol, high-density lipoprotein cholesterol, and uric acid concentrations,
      and blood pressure. RESULTS: Mean (+/- standard error of the mean) integrated
      plasma glucose response area for 2 h following a 75 g oral glucose load was
      significantly higher (13.4 +/- 0.4 vs. 11.0 +/- 0.4 mmol l-1, P < 0.001) in the
      hyperinsulinaemic group, as were the fasting triglyceride levels (2.4 +/- 0.2 vs.
      1.4 +/- 0.1 mmol l-1, P < 0.001) and uric acid (5.3 +/- 0.2 vs. 4.4 +/- 0.2 mmol
      l-1, P < 0.05) concentrations. In contrast, high-density lipoprotein
      concentrations were lower in the hyperinsulinaemic group (1.06.0.05 vs. 1.32 +/-
      0.05 mmol l-1, P < 0.001). In addition, blood pressure was higher in the
      hyperinsulinaemic group (136 +/- 5/87 +/- 2 vs. 123 +/- 2/82 +/- 1 mmHg, P <
      0.05). Furthermore, when each of the two groups were divided into obese (n = 16)
      and non-obese (n = 16) groups, all of the differences outlined above persisted.
      These changes were independent of age, gender distribution, generalized and
      abdominal obesity, cigarette smoking, and estimated physical activity.
      CONCLUSIONS: The cluster of changes subsumed under the heading of syndrome X are
      closely associated with hyperinsulinaemia (and presumably insulin resistance),
      and can be discerned irrespective of degree of obesity.

PMID- 8283161
TI  - Antivenom treatment in Vipera berus envenoming--report of 30 cases.
AB  - OBJECTIVES: To assess efficacy and safety of two equine F(ab')2 antivenoms
      currently used to treat envenoming by European vipers. DESIGN: Retrospective case
      review study. SETTING: Case records collected by the Swedish Poison Information
      Centre concerning patients treated in Swedish hospitals for bites by the common
      European adder, Vipera berus. SUBJECTS: Patients presenting with V. berus
      envenoming treated with antivenom (n = 30) and two groups of patients not given
      antivenom (n = 16 and n = 38). MAIN OUTCOME MEASURES: Clinical course and time in
      hospital were retrospectively studied and compared in patients treated or not
      treated with antivenom. RESULTS: There was a significantly lower incidence of
      extensive oedema (23 vs. 88%) and anaemia (10 vs. 50%) in the antivenom-treated
      group, and the hospital stay was shorter (median: 3 vs. 6 days). Antivenom
      treatment also resulted in prompt clinical improvement in the acute phase.
      Adverse effects consisting of urticaria and serum sickness occurred in 10% of the
      patients given antivenom. CONCLUSIONS: Antivenom treatment was associated with a
      reduced morbidity in severe V. berus envenoming. However, the occurrence of
      allergic side-effects is not negligible with this type of antivenom.

PMID- 8283162
TI  - Endogenous digoxin-like factor in acute myocardial infarction.
AB  - OBJECTIVES: The aim of the study was to test the hypotheses that the
      concentrations of endogenous digoxin-like factor (EDLF) are (i) increased in the
      initial period after acute myocardial infarction (AMI) and (ii) may contribute to
      the genesis of ventricular arrhythmias. DESIGN: Consecutive sample study.
      SETTING: An 800-bed city teaching hospital, primary hospitalized care centre.
      SUBJECTS: Fifty-four consecutive patients of both sexes with a first transmural
      AMI, 16 male patients with unstable angina pectoris and eight healthy subjects.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Time-course of the changes of plasma
      concentrations of EDLF (DELFIA digoxin fluoroimmunoassay) in patients during days
      1-14 after uncomplicated AMI and AMI complicated with ventricular fibrillation
      and congestive heart failure. RESULTS: Plasma concentrations of EDLF in patients
      on the 1st day after AMI were increased (1.25 +/- 0.26 ng ml-1 digoxin
      equivalents, P < 0.025) as compared with both healthy controls (0.34 +/- 0.06 ng
      ml-1) and patients with unstable angina pectoris (0.40 +/- 0.08 ng ml-1). On the
      1st day after AMI the plasma levels of EDLF in seven patients with primary
      ventricular fibrillation were higher (2.54 +/- 0.67 ng ml-1, P < 0.05) than in 47
      patients without ventricular fibrillation (1.05 +/- 0.27 ng ml-1). In 14 patients
      with AMI and congestive heart failure (class III, Killip), plasma concentrations
      of EDLF were significantly lower (0.32 +/- 0.09 ng ml-1, P < 0.01) than in 40
      patients with AMI without congestive heart failure (1.51 +/- 0.32 ng ml-1).
      Starting from the 2nd day of AMI, plasma EDLF decreased to the level of the
      control values (0.35 +/- 0.04 ng ml-1) and did not change during a 2-week period
      of observation. CONCLUSIONS: The results show an increase of plasma EDLF during
      the 1st day after AMI, and that higher plasma EDLF may be associated with the
      development of ventricular arrhythmias.

PMID- 8283163
TI  - Intestinal type of thromboangiitis obliterans (Buerger's disease).
AB  - Thromboangiitis obliterans (TAO) is a recurrent, inflammatory, segmental
      occlusive disease of distal limb arteries which may involve veins as well. Young
      smokers are predisposed to TAO. The intestinal vessels are rarely affected. We
      report the clinical, angiographic and histologic findings of a 23-year-old smoker
      with extended thrombophlebitis who developed severe abdominal angina and liver
      hypoxia due to occlusion of the coeliac artery and subtotal occlusion of the
      superior mesenteric artery. Two surgical bypassing procedures were followed by
      early graft occlusion. Subsequently, a plastic patch of the superior mesenteric
      artery and an aortohepatic bypass were performed. The literature since 1945
      pertinent to intestinal TAO is reviewed.

PMID- 8283164
TI  - A case of central diabetes insipidus with spontaneous remission after 8 years of
      the disease.
AB  - A 55-year-old male smoker developed polyuria and polydipsia in November 1983. A
      water deprivation study revealed a defect in the urine concentrating function,
      which was corrected by vasopressin. Plasma antidiuretic hormone (ADH) was not
      increased by smoking. His condition was well controlled by deamino-D-arginine
      vasopressin. However, since February 1992 he has become completely free from the
      need for medication to control his urine volume. Re-evaluation studies with water
      deprivation and smoking revealed dramatic improvements in the urine concentrating
      function and ADH response. A patient with idiopathic diabetes insipidus with
      spontaneous remission after 8 years is reported.

PMID- 8283165
TI  - A catastrophic antiphospholipid syndrome: the importance of high levels of
      warfarin anticoagulation.
AB  - We report the clinical observation of a 23-year-old woman affected by the so
      called 'catastrophic antiphospholipid syndrome'. Within a 3-month period she
      suffered a number of thrombotic events and haemolytic anaemia with
      thrombocytopenia and had high levels of immunoglobulins G and M and
      anticardiolipin antibodies associated with lupus anticoagulant activity. The
      severity of the clinical and laboratory changes is described and diagnostic and
      therapeutic difficulties are discussed. The apparent control of thrombotic events
      only with high levels of warfarin anticoagulation is stressed.

PMID- 8283166
TI  - Tissue plasminogen activator for hepatic vein thrombosis in paroxysmal nocturnal
      haemoglobinuria.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder thought
      to arise in a multipotent haemopoietic stem cell. A distinct clinical feature is
      a tendency to thrombosis, with a particular predilection for the hepatic veins
      (Budd-Chiari syndrome). We report here on two patients with PNH who developed
      hepatic vein thrombosis (HVT) and who were treated with tissue plasminogen
      activator (t-PA). Both patients had a marked clinical and radiological
      improvement following the t-PA treatment and remain well over 2 years and 6 years
      after the treatment. This method of thrombolysis for HVT occurring in PNH has
      only been reported in two previous patients with limited follow-up. We suggest
      that this therapy is a useful first-line treatment for PNH patients who develop
      HVT.

PMID- 8283167
TI  - Cytomegalovirus colitis in a patient with small-cell lung cancer.

PMID- 8283168
TI  - Clinical heterogeneity of idiopathic CD4+ T lymphocytopenia.

PMID- 8283169
TI  - Insulin-like growth factor in chronic liver disease.

PMID- 8283170
TI  - Immunohistological detection of human herpes virus 6 in formalin-fixed, paraffin
      embedded lung tissues.
AB  - Human herpes virus type 6 (HHV-6) infection is widespread in healthy individuals.
      The only definite disease association is with exanthem subitum in infants though
      the virus has been linked with a variety of other diseases including interstitial
      pneumonitis in bone marrow allograft recipients. In order to investigate the role
      of HHV-6 in the latter disease we have developed an optimised staining method for
      the demonstration of specific antigen in routinely processed post-mortem tissues.
      Formalin-fixed, paraffin-embedded lung tissue from 8 immunocompromised patients
      who died from interstitial pneumonitis was subjected to immunoperoxidase staining
      with monoclonal antibodies against HHV-6, cytomegalovirus (CMV), and adenovirus,
      using a modified avidin-biotin complex (ABC) method. Staining for HHV-6 was
      obtained in 6 of the 8 patients studied and was present in pneumocytes and
      macrophages. CMV and adenovirus antigens were identified in 4 and 6 patients,
      respectively. Whilst the lung tissue of 6 patients contained more than one virus,
      there was no evidence of cross-reactivity between the monoclonal antibodies. We
      demonstrated that accurate localisation of HHV-6 using monoclonal antibodies is
      possible in post-mortem lung tissue and conclude that either HHV-6 alone or in
      combination with other viruses may play a role in the development of interstitial
      pneumonitis following bone marrow transplantation or chemotherapy.

PMID- 8283171
TI  - Lymphocyte responses and virus excretion as risk factors for intrauterine
      infection with cytomegalovirus.
AB  - Serological screening of pregnant women in this and a previous study identified
      28 cases of primary infection with cytomegalovirus, 7 (25%) of whom transmitted
      the infection to their fetuses. Risk factors for intrauterine infection were: 1)
      age less than 20 years, 2) Caucasian rather than non-Caucasian race, 3) a weak
      response to cytomegalovirus antigen in the lymphocyte transformation test, and 4)
      the excretion of cytomegalovirus in the urine. The greatest risk was when a weak
      lymphoproliferative response was detected in combination with a positive result
      for virus isolation, in which case the chance of fetal infection was 83%. Despite
      these associations, there was one important anomalous result of a woman who
      demonstrated a strong lymphocyte response during pregnancy and a negative result
      for virus isolation, but who gave birth to an infected baby who developed
      unilateral hearing loss.

PMID- 8283172
TI  - Heroin addicts infected by HBV and HIV have a low prevalence of HBV DNA in
      peripheral blood mononuclear cells.
AB  - Several reports show that the prevalence of HBV (hepatitis B virus) carriers in
      HIV (human immunodeficiency virus) infected populations is significantly higher
      than in HIV seronegative individuals, independent of the risk group for HIV, that
      is, homosexuals or drug abusers. In this context, evaluation of the simultaneous
      presence of HBV and HIV in PBMCs (peripheral blood mononuclear cells) is of
      particular interest for at least 2 reasons: 1) the possible reciprocal influence
      of the 2 viruses when they infect the same cell; 2) the possibility that HIV
      induced hematological disorders could indirectly influence the settling of HBV in
      blood cell populations. We report data on the frequency of PCR positivity for HBV
      DNA in PBMCs from 62 HIV infected patients, rigorously selected by risk group,
      that is, intravenous use of heroin for at least 3 years and syringe promiscuity.
      Sixty-seven HIV negative individuals who never used any drug formed the control
      group. The analysis of the cases positive for HBV DNA in PBMCs showed that: 1)
      the overall prevalence of PCR positivity found in HIV infected patients was
      significantly lower than that registered in the control group; 2) PCR positivity
      among the subjects who were HBsAg negative and anti-HBV positive was extremely
      low in the HIV infected patients (3.7%) but quite frequent in the HIV negative
      subjects (37.0%). The results support the hypothesis that, unlike the HIV
      negative individuals, our HIV infected patients exhibited HBV DNA in PBMCS almost
      exclusively when they presented with active HBV replication.

PMID- 8283173
TI  - Demonstration of hepatitis C virus genome in saliva and urine of patients with
      type C hepatitis: usefulness of the single round polymerase chain reaction method
      for detection of the HCV genome.
AB  - The possible transmission routes of hepatitis C virus (HCV) in patients without
      overt parenteral exposure (sporadic or community acquired form) were examined.
      Saliva and urine specimens obtained from type C hepatitis patients, whose sera
      were positive for the HCV genome, were examined by reverse transcription and
      polymerase chain reaction (RT-PCR). By analyzing the factors that influenced the
      detection of the HCV genome by PCR, we developed a single round method which
      enabled semiquantitative detection with higher sensitivity than that obtained
      with nested PCR. Single round PCR revealed that 34.8% (8 of 23) of saliva and
      56.5% (13 of 23) of urine specimens from patients with type C hepatitis contained
      the HCV genome. The amounts of HCV genome in saliva and urine specimens
      correlated with those in serum. The relative amounts of HCV genome in serum,
      saliva, and urine from a chronic type C hepatitis patient were determined by
      comparing the reciprocal of the smallest volume of the specimens in which the PCR
      products were visualized in agarose gels (PCR units/ml), and the values were 1 x
      10(5), 5 x 10(1), and 3 x 10(1) PCR units/ml for serum, saliva, and urine
      specimens, respectively.

PMID- 8283174
TI  - Attenuation of a reactivated cardiovirulent coxsackievirus B3: The 5'
      nontranslated region does not contain major attenuation determinants.
AB  - To investigate the molecular basis of pathogenicity of Coxsackieviruses, a virus
      was reactivated by transfection from a full-length cDNA clone derived from
      cardiovirulent Coxsackievirus B3 (CVB3). The reactivated virus, rCVB3, was
      passaged serially in human dermatofibroblasts (HDF). No cytopathic effect was
      observed up to 12 days after inoculation with rCVB3 or early-passage virus,
      although disintegration of the monolayers was observed with late-passage virus
      (10th to 14th passages). Approximately 10% of HDF inoculated with rCVB3 were
      positive for viral antigens by immunofluorescence using enterovirus- or CVB3
      specific monoclonal antibodies. These observations, together with the low
      infectivity titre of rCVB3 in HDF, suggests that HDF initially support only
      carrier state infection. After the 14th passage, the cardiovirulence of passaged
      virus (p14V) in mice was attenuated by a factor of > 10(4). Phenotypic changes of
      plaque size were also noticed in p14V: An attenuated variant (p14V-1) that
      produced larger plaques than rCVB3 in Vero cells has been plaque purified. The 5'
      terminus of the genome of attenuant p14V-1 was amplified by polymerase chain
      reaction (PCR) and its sequence determined. Only one point mutation was found
      within the 5'-nontranslated region (5'NTR) at position 690 (A to U) compared to
      the viral RNA sequence obtained for rCVB3. An intertypic chimeric virus was
      reactivated from a cDNA clone after replacing the 5'-terminal 891 nucleotides of
      the wild-type genome with the corresponding region of the attenuant p14V-1. This
      chimeric virus, CB3/p14V-1/1, produced wild-type plaques in Vero cells and showed
      cardiovirulence similar to that of rCVB3 in mice.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8283175
TI  - Herpes simplex virus type 1 genes in human mononuclear cells and affecting cell
      mediated immunity.
AB  - To evaluate whether herpes simplex virus type 1 (HSV-1) replicates in freshly
      isolated human mononuclear cells (HMNC) and results in cell-mediated immunity,
      HMNC purified from the peripheral blood of a healthy HSV-1-seronegative
      individual were infected with HSV-1 (KOS strain). The kinetic data indicated that
      HSV-1 particles were detected in HMNC at 9 hr postinfection, and the highest HSV
      1 titer was obtained at 24 hr postinfection. It was found that the newly
      synthesized HSV-1 DNA increased in HMNC corresponding to the duration of time
      postinfection. The HSV-1 tk mRNA was detected in HSV-1-infected HMNC by Northern
      blot analysis. The Western blot analysis indicated that the HSV-1-infected HMNC
      could express the viral proteins. These results suggest that HSV-1 replicates in
      freshly isolated HMNC and expresses its DNA, RNA, and proteins. Interleukin-2 (IL
      2) production and cell-mediated cytotoxicity (CMC) were also determined in HSV-1
      infected HMNC but were lower than those found in uninfected HMNC. On the other
      hand, HSV-1 DNA was detectable in HMNC of patients suffering from recurrent HSV-1
      infection. The results show that, in the recrudescent phase, the patients' HMNC
      contain more HSV-1 DNA than in the convalescent phase. We conclude that the
      impairments of immune responses are related to the infection of HMNC by HSV-1.

PMID- 8283176
TI  - Seroepidemiology of hepatitis A and hepatitis B virus infection in a Gurkha
      community in Singapore.
AB  - The overall prevalence of hepatitis A virus (HAV) infection among the Gurkhas and
      their families stationed in Singapore was 83.2%, with antibody to HAV detected in
      67 (38.1%) of 176 children under 5 years of age, 121 (76.6%) of 158 children
      between 5 and 14 years, and 600 (97.9%) of 613 older children and adults over age
      15 years. Children born in Singapore (102/223 or 45.7%) had a significantly lower
      crude prevalence than those born in Nepal (85/110 or 77.3%) (P < 0.000001). The
      age-adjusted difference in prevalence was also statistically significant (P <
      0.001). Susceptible children had a high risk of acquiring HAV infection when they
      travelled to Nepal. As for hepatitis B virus (HBV) infection, the prevalence of
      hepatitis B surface antigen (HBsAg) was 2.8%, with a higher rate in males (20/560
      or 3.6%) than in females (6/384 or 1.6%). The highest HBsAg prevalence (4/26 or
      15.4%) was in young adult Gurkhas 15-19 years of age. No significant difference
      in the crude prevalence of HBV markers was noted between children born in
      Singapore (45/224 or 20.1%) and those born in Nepal (19/107 or 17.8%). Even after
      age adjustment, the difference remained insignificant. The prevalence of HBV
      markers of children of seropositive parents (27/156 or 17.3%) was not
      significantly higher than that of seronegative parents (19/131 or 14.5%). Married
      men had a significantly higher age-adjusted prevalence of infection than
      unmarried men (45.4% and 32.4%, respectively; P < 0.05). Seropositivity of one
      spouse was significantly correlated with the seropositivity of the other (P <
      0.05), suggesting a role for heterosexual transmission of HBV infection.

PMID- 8283177
TI  - Transfer of humoral immunity against cytomegalovirus proteins following
      transplantation of T-cell-depleted allogeneic bone marrow from seropositive
      donors.
AB  - Previous work by Grob et al. [Lancet i: 774, 1987] has demonstrated that
      allogeneic, T-cell-depleted bone marrow transplant recipients have a better
      prognosis for reactivated cytomegalovirus (CMV) infection if their donor is also
      immune. It was proposed that adoptively transferred humoral immunity was
      responsible for the protective effect of active infection. Immunoblot analysis
      using purified virions was used here to examine pre- and posttransplant antibody
      responses of seropositive recipients who had undergone active viral infection
      after transplantation. Immunoblots were assessed for the numbers of polypeptides
      recognised and reactivity against individual polypeptides. Immunoblots were also
      scanned by quantitative densitometry, and the intensity of antibody responses
      against total viral protein and individual polypeptides was determined. Sera from
      recipients with immune donors exhibited a secondary-type immune response in terms
      of both intensity and polypeptide specific pattern of antibody reactivity,
      compared with those recipients with nonimmune donors. In particular, recipients
      with immune donors appeared to show a greater reactivity against a protein of
      M(r) 55,000; this may represent the envelope glycoprotein gB, which is a major
      target for neutralising antibodies, and might also be utilised for preparing an
      effective vaccine for CMV.

PMID- 8283178
TI  - Novel assay for the detection of immunoglobulin G antihuman immunodeficiency
      virus in untreated saliva and urine.
AB  - Epidemiological evidence and laboratory studies indicate that human
      immunodeficiency virus type 1 (HIV 1) is rarely, if ever, transmitted in saliva
      or urine. In that both specimens are easy to collect, each may be a useful
      alternative to serum specimens for anti-HIV screening. A rapid, simple, and
      robust IgG-capture enzyme-linked immunosorbent assay (GACELISA) suitable for the
      detection of anti-HIV 1 and 2 in saliva and urine was developed. Following
      optimisation of the assay, 177 salivary and 568 urine specimens collected from
      individuals of known serostatus were investigated. The assay was 100% sensitive
      on 50 salivary (median OD/CO = 8.9) and 126 urinary (median OD/CO = 8.6)
      specimens collected from anti-HIV-positive patients. The specificity was 100% on
      127 salivary specimens (median OD/CO = 0.37) and 422 urinary specimens (median
      OD/CO = 0.39) collected from anti-HIV-negative individuals. These findings
      demonstrate that GACELISA HIV 1 + 2 tests on saliva or on urine are an accurate
      alternative to a conventional anti-HIV test of blood. This assay is satisfactory
      for surveillance purposes and, with appropriate precautions, could be used
      clinically.

PMID- 8283179
TI  - Specific deletions in the hepatitis B virus core open reading frame in patients
      with chronic active hepatitis B.
AB  - The polymerase chain reaction (PCR) and DNA sequencing were used to examine
      genomic variation in the pre-core/core open reading frame of the hepatitis B
      virus (HBV) in chronically infected patients. Gel electrophoresis of
      amplification products showed the presence of shortened forms of the core gene in
      addition to the full length product. These shortened forms were seen only in
      patients with chronic active hepatitis (CAH) seropositive for HBeAg and not in
      patients with chronic persistent hepatitis (CPH) or HBeAg minus CAH. Cloning and
      DNA sequencing revealed the presence of a number of overlapping deletions within
      the core gene, the majority being in-frame, which were clustered within aa 81-114
      of the core gene product. These deletions were found in patients with CAH from
      different racial and geographical backgrounds, whereas PCR analysis of the
      surface and X open reading frames showed no shortened forms suggesting deletions
      to be specific to the core gene in these patients. Because the product of the
      core gene--the HBV core antigen--is believed to be the major target for T-cell
      mediated liver damage, it seems likely that the products of core genes carrying
      deletions will alter immune recognition and may be of importance in the
      progression of inflammatory liver damage.

PMID- 8283180
TI  - Quantitative analysis of herpes simplex virus DNA in cerebrospinal fluid of
      children with herpes simplex encephalitis.
AB  - Herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) of children with
      herpes simplex encephalitis (HSE) was quantified and typed using the polymerase
      chain reaction (PCR) assay. During the acute phase, HSV-DNA was detected in the
      CSF of 13 patients with HSE, including 5 neonates. A restriction profile of the
      PCR products cleaved with the restriction enzymes XhoI and BglII showed that 2
      neonatal samples were HSV-2, and the remainder were HSV-1. The amount of HSV-DNA
      in the initial CSF ranged from 10(2)-10(5) copies/ml. A significantly greater
      number of HSV-DNA copies was detected in neonates than in older children (mean
      3.9 vs. 2.5, log 10 copies/ml p < .05). Except for one patient, the amount of HSV
      DNA decreased gradually with acyclovir therapy. These results show that a
      quantitative PCR assay is applicable not only to the diagnosis of HSE but also
      for monitoring the response to antiviral drugs.

PMID- 8283181
TI  - Current seroepidemiology of rubella virus infection among female residents in
      Taiwan.
AB  - To examine the epidemiological characteristics of rubella virus infection on
      Taiwan Island and in Orchid and Pescadore islets, a community-based survey was
      carried out in 19 townships and metropolitan precincts randomly selected through
      stratified sampling. Serum specimens of 4,770 healthy girls and women randomly
      sampled from study areas were screened for the rubella antibody by passive latex
      agglutination testing and confirmed by enzyme-linked immunosorbent assay. A total
      of 2,934 subjects were antibody positive, giving a prevalence of 61.5%. The mean
      +/- standard deviation of rubella IgG index was 2.51 +/- 0.37. The seropositive
      rate increased with age in all residential areas and ethnic groups. The age
      pattern indicated that the regular 10-year cycle of rubella epidemic was no
      longer existent after 1978. A higher prevalence was observed in the eastern
      island and Orchid Islets compared with other areas. The highest seropositive rate
      was found in Orchid Islets. The overall seronegative rate was 62.9% for females <
      20 years of age and 36.9% for women between the ages of 20 and 29 years. With
      such a high susceptible density among girls and women of child-bearing ages as
      well as the endemicity of rubella virus infection in Taiwan, mass vaccination
      against rubella should be enforced in order to prevent possible future outbreaks
      of the congenital rubella syndrome.

PMID- 8283182
TI  - Accelerated schedule of hepatitis B vaccination in patients with hemophilia.
AB  - Early development of immunity after hepatitis B vaccination is particularly
      important for patients such as hemophiliacs, at high risk for acquiring hepatitis
      B from potentially infectious plasma-derived concentrates. The purpose of this
      study was to evaluate whether or not protective antibody titers could be achieved
      quickly and maintained in hemophiliacs by an accelerated vaccination schedule. A
      yeast-recombinant hepatitis B vaccine (Engerix B, SKF Ritt) was given
      subcutaneously in the deltoid region and repeated 2 and 6 weeks later to 85
      hemophiliacs negative for hepatitis B virus (HBV) markers. After the first 22
      patients had been enrolled, a modification of the schedule involving a fourth
      booster dose 24 weeks after the first dose of vaccine was applied to the next 63
      consecutive vaccines. Fifty-three percent of vaccinees had antibody titers to
      hepatitis B surface antigen (anti-HBs > or = 10 mlU/ml) by week 6, even though
      the mean titers of anti-HBs were somewhat lower than those achieved historically
      in normal individuals. The protection rate had increased to 87% by week 10, one
      month after the third dose of vaccine, and to 93% by week 24. One year after
      starting vaccination, the rate for the vaccinees who did not receive the fourth
      booster dose was 71%, and 96% for those who did receive the fourth dose, with
      only 2 patients not responding despite the booster dose. It is concluded that
      even though the accelerated schedule of immunization produced rapidly high rates
      of protective antibody titers, a booster dose is required to obtain higher titers
      and provide more persistent immunity.

PMID- 8283183
TI  - Hepatitis C viral RNA titers in serum prior to, during, and after oral treatment
      with ribavirin for chronic hepatitis C.
AB  - Ten patients with biopsy verified chronic hepatitis C virus (HCV) infection were
      treated with oral ribavirin at a dose of 1,000-1,200 mg per day in two divided
      doses for 12 weeks. Serum alanine aminotransferase (ALT) levels and hepatitis C
      viral ribonucleic acid (RNA) levels in serum were followed prior to, during, and
      12 weeks posttreatment. ALT levels decreased significantly in all patients during
      therapy from a mean level of 3.21 mukat/l (range 1.22 to 7.79) before, to 1.25
      mukat/l (range 0.78 to 2.04) at the end of treatment (P < 0.005). Hereafter,
      relapse to pretreatment levels was seen within 12 weeks after treatment stop. The
      hepatitis C viral RNA levels decreased from a mean 10 log titer of 4.1 (range 1
      6) before treatment to 3.4 (range 1-5) at treatment stop. Five patients did not
      change their HCV RNA titers during treatment. Twelve weeks posttreatment only 3
      patients had lower titers than prior to treatment. We conclude that oral
      ribavirin seems to reduce the viral load, at least temporarily, in some patients
      with chronic viremic HCV infection. Further studies are needed to evaluate fully
      the effect of oral ribavirin on chronic HCV infection.

PMID- 8283184
TI  - Developmental analysis reveals labial and subradular ganglia and the primary
      framework of the nervous system in nudibranch gastropods.
AB  - Previous ultrastructural observations on late stage larvae of dorid nudibranchs
      (Gastropoda, Opisthobranchia) revealed two pairs of ganglia within the base of
      the foot that do not have obvious counterparts in existing descriptions of other
      gastropod larvae [Chia and Koss (1989). Cell Tiss. Res. 256:17-26.] One of these
      ganglionic pairs has been implicated in the initiation of settlement preceding
      metamorphosis [Arkett et al. (1989). Biol. Bull. 176:155-160.] By examining
      neurogenesis in sequential larval stages, I have found that the pattern of
      connectives and commissures associated with these enigmatic ganglia is comparable
      to patterns found in less consolidated adult nervous systems of chitons,
      monoplacophorans, and archaeogastropods. These comparative data suggest that the
      two pairs of ganglia in dorid nudibranch larvae are homologues of labial and
      subradular ganglia. The labial ganglia become incorporated into the cerebral
      ganglia at metamorphosis. In an attempt to integrate anatomical and developmental
      observations with behavioral and neurophysiological results, I suggest that
      receptor cells of the larval labial ganglia may become postmetamorphic primary
      mechanoreceptors of the oral tube, which have central cell bodies within the
      "cerebral" ganglia and which help coordinate feeding. Results of this study also
      address a larger evolutionary issue by questioning the traditional model of an
      ancestral molluscan nervous system that consists of four longitudinal nerve cords
      that arise from separate sites along a circumesophageal nerve ring. This pattern
      results from secondary connections in nudibranchs and possibly other molluscs.
      The primary condition of a single axon bundle emerging from each cerebral
      ganglion is more similar to the developing nervous system in polychaete annelids
      than what has been recognized previously.

PMID- 8283185
TI  - Aspects of early postnatal development of cortical neurons that proceed
      independently of normally present extrinsic influences.
AB  - To examine the contribution of local versus extrinsic influences on postnatal
      development of cortical neurons, we compared the maturation of deep
      (infragranular) layer neurons in isolated slices of neocortex grown in
      organotypic culture to a similar population of neurons developing in vivo. All
      slice cultures were prepared from sensorimotor cortices of newborn mice (P0) and
      neurons in these cultures were examined at daily intervals during the first 9
      days in vitro (DIV). The maturational state of neurons developing in vivo over
      this same time period was assessed in acute slices prepared from animals of
      equivalent postnatal age, P1-P9. Electrophysiological recordings were obtained
      from neurons in both cultured and acute slices, using Lucifer yellow filled whole
      cell recording electrodes, enabling subsequent morphometric analysis of the
      labeled cells. We report significant changes in both cellular morphology and
      electrical membrane properties of these deep layer cortical neurons during the
      first week in culture. Morphological maturation over this time period was
      characterized by a two- to three-fold increase in cell body size and total
      process length, and an increase in dendritic complexity. In this same population
      of cells a three-fold decrease in input resistance and changes in the action
      potential waveform, including a two-fold decrease in the AP duration, also occur.
      The degree of morphological and electrophysiological differentiation of
      individual neurons was highly correlated across developmental ages, suggesting
      that the maturational state of a cell is reflected in both cellular morphology
      and intrinsic membrane properties. A remarkably similar pattern of neuronal
      maturation was observed in neurons in layers V, VI/SP examined in acute slices
      prepared from animals between P1-P9. Because our culture system preserves many
      aspects of the local cortical environment while eliminating normal extrinsic
      influences (including thalamic, brainstem, and callosal connections), our
      findings argue that this early phase of neuronal differentiation, including the
      rate and extent of dendritic growth and development of AP waveform, results from
      instructive and/or permissive local influences, and appears to proceed
      independently of the many normally present extrinsic factors.

PMID- 8283186
TI  - Synapse elimination from the mouse neuromuscular junction in vitro: a non-Hebbian
      activity-dependent process.
AB  - The effect of action potentials on elimination of mouse neuromuscular junctions
      (NMJ) was studied in a three-compartment cell culture preparation. Axons from
      superior cervical ganglion or ventral spinal cord neurons in two lateral
      compartments formed multiple neuromuscular junctions with muscle cells in a
      central compartment. The loss of synapses over a 2-7-day period was determined by
      serial electrophysiological recording and a functional assay. Electrical
      stimulation of axons from one side compartment during this period, using 30-Hz
      bursts of 2-s duration, repeated at 10-s intervals, caused a significant increase
      in synapse elimination compared to unstimulated cultures (p < 0.001). The extent
      of homosynaptic and heterosynaptic elimination was comparable, i.e., of the 226
      functional synapses of each type studied, 111 (49%) of the synapses that had been
      stimulated were eliminated, and 87 (39%) of unstimulated synapses on the same
      muscle cells were eliminated. Also, simultaneous bilateral stimulation caused
      significantly greater elimination of synapses than unilateral stimulation (p <
      0.005). These observations are contrary to the Hebbian hypothesis of synaptic
      plasticity. A spatial effect of stimulus-induced synapse elimination was also
      evident following simultaneous bilateral stimulation. Prior to stimulation, most
      muscle cells were innervated by axons from both side compartments, but after
      bilateral stimulation, muscle cells were predominantly unilaterally innervated by
      axons from the closer compartment. These experiments suggest that synapse
      elimination at the NMJ is an activity-dependent process, but it does not follow
      Hebbian or anti-Hebbian rules of synaptic plasticity. Rather, elimination is a
      consequence of postsynaptic activation and a function of location of the muscle
      cell relative to the neuron. An interaction between spatial and activity
      dependent effects on synapse elimination could help produce optimal refinement of
      synaptic connections during postnatal development.

PMID- 8283187
TI  - Different forms of 130 kD connective tissue protein are specific for boundaries
      in the nervous system and basement membrane of muscle cells in leech.
AB  - The nervous system and muscle tissue of the leech express two different organ
      specific forms of connective tissue protein. The nervous system-specific form
      appears in regional boundaries separating cell bodies, axonal tracts and areas of
      the neuropile during late embryogenesis. In contrast, the muscle-specific form
      appears earlier during development in the basement membrane of muscle cells. In
      extraction experiments both forms behave like extracellular matrix proteins and
      because of their molecular weight, are considered members of a group of cell type
      specific 130 kD proteins (leech gp130s). However, the two forms differ in their
      posttranslational modification. As determined by Con A and lentil lectin affinity
      chromatography, only the nervous system-specific, but not the muscle-specific
      form, has fucosylated and high mannose N-linked carbohydrates. These differences
      in the developmental onset and glycosylation suggest that nervous system-specific
      and muscle-specific connective tissue proteins are regulated differently and
      participate in different molecular interactions.

PMID- 8283188
TI  - Sexually dimorphic neuron number in lumbosacral dorsal root ganglia of the rat:
      development and steroid regulation.
AB  - Rats possess a sexually dimorphic neuromuscular system that controls penile
      reflexes critical for copulation. This system includes two motor nuclei in the
      lumbar cord and their target musculature in the perineum. The spinal nucleus of
      the bulbocavernosus (SNB) and the dorsolateral nucleus (DLN) motoneuron
      populations and their target perineal muscles are much larger in males than in
      females. The sex difference in motoneuron number develops via androgen-regulated
      differential cell death during the perinatal period; androgen also regulates
      retention of the target muscles. The developmental pattern and steroid
      sensitivity of peripheral afferents to the SNB/DLN motor nuclei were previously
      unknown. In order to characterize the peripheral sensory component of the
      dimorphic SNB/DLN system, the neurons of the relevant dorsal root ganglia (DRGs)
      were quantified in terms of number, size, and androgen sensitivity at various
      perinatal ages. DRG neuron number is greatest prenatally, then decreases in both
      sexes after birth; the timing and pattern of neuron number development are
      similar to those seen in the SNB and DLN. Postnatally, males have more DRG
      neurons than females, as a result of greater neuron death in the DRGs of females.
      Females treated with testosterone propionate during the perinatal period exhibit
      masculine development of DRG neuron number. Thus, the normal development of DRG
      neuron number parallels that of the SNB/DLN motor nuclei and target muscles in
      pattern and timing, is sexually dimorphic, and is regulated by androgen.

PMID- 8283189
TI  - How useful are models of natural history in clinical decision making and clinical
      research?

PMID- 8283190
TI  - Use of global assessment measures in dementia drug trials.
AB  - I argue in this paper that the use of a global clinical impression of change as a
      primary measure in dementia drug trials is appropriate, given that we do not yet
      understand clearly enough what Alzheimer's disease looks like as it gets better.

PMID- 8283191
TI  - The etiology of the anemia of chronic disease and infection.
AB  - Anemia of infection and chronic disease has traditionally been considered a
      disorder associated with infections/inflammation. We instead propose that the
      anemia of infection and chronic disease confers protection from pathogen or
      neoplastic invasion. There is substantial microbiological and medical research
      that indicates that the anemia of infection and chronic disease may be a non
      specific immunological defense. We suggest it is analogous to fever, which was
      also originally considered to be a disorder in need of treatment but which is now
      seen as a positive response of the host to microbial invasion. We suggest that
      these two non-specific defenses against microorganism proliferation may have
      evolved together as complementary strategies the body employs to ward off
      disease.

PMID- 8283192
TI  - A Markov model of the natural history of prostate cancer.
AB  - The objective of this study was to lay a foundation for future cost-benefit
      analyses evaluating the public health impact of treatment and screening protocols
      for prostate cancer. Specifically we wanted to define the relative impact on
      cancer-specific mortality rates of the individual epidemiological components:
      pathological incidences by age groups, cancer progression rates, and the effect
      of competing causes of death, assuming expectant management (i.e. no definitive
      treatment). A biological model of prostate cancer incidence and progression was
      converted into a standard Markov tree where competing causes of death could
      occur. Weighted averages of progression rates were obtained from clinical
      studies. Separate cohorts of 30 year old black and white men were followed for 50
      years. The model yielded cancer-specific mortality rates, overall mortality
      rates, and pathologic prevalences for both white and black males, consistent with
      the literature. Sensitivity analyses showed that of all the parameters studied,
      the pathological incidence of cancer in men under 50 years of age had the
      greatest impact on the cancer-specific mortality rates. Also important was the
      annual probability of progression of A1 lesions. However the other parameters
      including pathological incidence in older males, and progression from locally
      extensive to metastatic lesions had much smaller effects. In summary, this model
      correlates the clinical literature with the epidemiology of prostate cancer and
      can be used for further decision analyses. We recommend that future research be
      done to more precisely quantify the pathological incidence of prostate cancer in
      men under 50-60 years of age. More certainty is also needed before generalizing
      the results of relatively small A1 series to millions of men, since A1
      progression rates critically affect the eventual cancer-specific mortality.
      Enough uncertainty remains at this point however, that we cannot advocate
      widespread screening for prostate cancer until its merit be demonstrated either
      by the definitive long term study, or by examination of costs and quality-of-life
      adjusted benefits.

PMID- 8283193
TI  - Habitual sleep durations and health in a 50-65 year old population.
AB  - Several studies have suggested that individuals with long or short sleep
      durations are at greater risk for adverse outcomes relative to individuals
      sleeping 7-8 hours a night. The mechanisms leading to these results have never
      been fully explained, but individual differences in how long an individual sleeps
      are usually considered to reflect lifestyle rather than disease. Alternatively,
      individuals may sleep a particular amount because of characteristics of their
      sleep physiology. In this study, we examined population-based data on the
      associations between sleep duration and several symptoms of sleep-related
      disease, reported snoring and daytime sleepiness. Results from 1877 independently
      living individuals between the ages of 50 and 65 years suggested that long, but
      not short, sleep durations were related to greater reported snoring. Higher
      levels of reported snoring and daytime sleepiness, but not habitual sleep
      duration, were related to measures of disease and lower psychosocial function. We
      suggest that future epidemiologic studies use such additional items as potential
      indicators of sleep-related disease.

PMID- 8283194
TI  - The risk of multiple sclerosis in the U.S.A. in relation to sociogeographic
      features: a factor-analytic study.
AB  - The multiple sclerosis (MS) case-control ratio by state originating from the U.S.
      veteran series from World War II (Kurtzke Neurology 1979; 29: 1228-1235) was
      geographically compared with 46 sociogeographic variables from the period 1935
      1958. Latitude was, by far, the variable most closely associated with MS in
      univariate testing. Multivariate analysis by factor analysis revealed that the MS
      rate was associated with 2 independent settings ("factors"). The first one was
      defined mainly socioeconomically and was characterized by indicators of higher
      affluence; better nutrition with a higher meat consumption in particular, and a
      higher sanitary level were the prominent features. The second MS-related bundle
      comprised characteristics of a colder climate along with further dietary
      variables (i.e. a diet low in fish and high in dairy products). The findings
      suggest a possible interaction of both socioeconomic and geoclimatic features in
      the etiology of MS; sanitation, diet and climate being of particular interest.

PMID- 8283195
TI  - Selection bias in electrophysiologically-guided therapy of sustained ventricular
      tachyarrhythmias.
AB  - To analyze if patient selection bias could contribute to the improved prognosis
      reported for ventricular tachycardia (VT) and ventricular fibrillation (VF) when
      therapy is guided by electrophysiologic studies (EPS), we studied 90 consecutive
      patients admitted to a tertiary referral center with recent VT/VF who were
      candidates for EPS. Seventeen patients (19%) died during the initial hospital
      admission, and 30 (33%) died after discharge. Survival probability was 0.83 (95%
      confidence interval [CI], 0.74-0.90); 0.67 (95% CI, 0.56-0.75); and 0.53 (95% CI,
      0.42-0.63) at 1 month, 1 year, and 3 years, respectively. Of the 56 patients
      (62%) who underwent EPS during their initial hospitalization, only 1 died during
      that admission. Patients in whom EPS could not be performed had characteristics
      associated with a poorer prognosis. NYHA functional class (p = 0.005), inability
      to perform baseline EPS (p = 0.003) and use of digoxin (p = 0.016) were
      independent predictors of death. Early in-hospital mortality in patients with
      VT/VF remains high. Thus, omission of these deaths in reports of EPS-guided
      therapy creates incomplete, biased cohorts. Furthermore, there may be a bias
      toward a healthier population among hospital survivors undergoing EPS. These
      findings may contribute to better outcomes in current series compared to
      historical controls.

PMID- 8283196
TI  - Ten-year change in the use of medical drugs among the elderly--a longitudinal
      study and cohort comparison.
AB  - Longitudinal changes and cohort differences from 1979 to 1989 in the use of
      prescribed and non-prescribed medical drugs were examined and the connections of
      drug use to various background variables were analysed in the framework of the
      Tampere Longitudinal Study of Ageing. In the longitudinal study random samples of
      men and women born in 1900-09 and 1910-19 (738 persons) were interviewed in 1979
      and the survivors (62%) were interviewed again in 1989. In the cohort comparison
      the 60-69-year-olds studied in 1979 (364 persons) were compared with the 60-69
      year-olds in 1989 (395 persons). In the longitudinal setting the number of
      prescribed drugs increased. In 1989 2 or 3 in 10 persons used at least five
      prescribed drugs simultaneously. In the cohort comparison there were no
      differences in the number of prescribed drugs between the two groups of 60-69
      year-olds. Use was connected with multimorbidity and poor self-rated health. Both
      the longitudinal comparison in the group born in 1910-19 and the cohort
      comparison revealed a significant increase in the use of non-prescribed drugs.
      The use of analgesics was connected with sex, occupational class, self-rated
      health and feelings of loneliness. In the use of vitamins, no connection was
      found with health variables, but they were mostly used by white-collar employees
      and women. However, when all these variables were controlled for, both analgesics
      and, in particular, vitamins were used more in 1989 than in 1979. The results
      suggest that the increase in the use of non-prescribed drugs is mainly due to
      social and historical factors, by changes both in drug policies, health culture
      and health behaviour of elderly persons.

PMID- 8283197
TI  - Determining a minimal important change in a disease-specific Quality of Life
      Questionnaire.
AB  - This study was carried out to determine whether the minimal important difference,
      in evaluative quality of life instruments which use a 7-point scale, is similar
      across individual domains and for both improvement and deterioration. Thirty nine
      adults with asthma were studied, using an 8 week cohort with assessments at 0, 4
      and 8 weeks. The outcomes were the Asthma Quality of Life Questionnaire and
      global rating of change. For overall asthma-specific quality of life and for all
      individual domains (activities, emotions, symptoms), the minimal important
      difference of quality of life score per item was very close to 0.5 (range: 0.42
      0.58); differences of approximately 1.0 represented a moderate change (range:
      0.77-1.51); differences greater than 1.5 represented large changes. Changes for
      improvement and deterioration were very similar. The changes in quality of life
      score that represent a minimal important difference are very similar to those
      observed for other evaluative instruments. The observation that the minimal
      important difference is consistent across domains and for both improvement and
      deterioration will facilitate interpretation of results of studies examining
      quality of life.

PMID- 8283198
TI  - Accuracy of family history of cancer obtained through interviews with relatives
      of patients with childhood sarcoma.
AB  - The purpose of this study was to determine the accuracy of reporting of invasive
      cancer by relatives for family studies. First, we attempted to evaluate whether a
      lower than expected cancer rate found in second-degree relatives of children with
      soft-tissue sarcoma was a result of underreporting. Second, we evaluated the
      accuracy of reported cancer in two data sets by comparing reported cancer
      information with documentation by medical records and death certificates. We
      obtained medical histories from a primary informant, usually the proband's
      parent, on 346 first- and 784 second-degree relatives of 68 childhood and
      adolescent soft-tissue sarcoma patients. To investigate underreporting by the
      primary informant we conducted an individual interview with each adult relative
      or proxy. Primary informants reported 22 cancers in first-degree relatives, all
      confirmed as invasive cancer, and 71 cancers in second-degree relatives with 50
      of 67 for which documentation confirmed as invasive. Of 715 individual informants
      contacted, 15 additional cancers were reported, including 5 confirmed as
      invasive. The number of first-degree relatives with confirmed invasive cancers
      was within the expected range; however, the number of cancers in second-degree
      relatives was below the expected range (observed/expected = 0.51 (54/105.5) 95%
      confidence interval (CI) = 0.39-0.67). Thus, the lower than expected number of
      cancers in second-degree relatives was not attributable to underreporting by a
      single informant or inability to obtain documentation. The overreporting of 25
      cancers (24.5%) in second-degree relatives, indicates the need to document all
      reported cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283199
TI  - The quest for the etiology of mental disorders.
AB  - The evidence for the etiological basis of mental disorders is insufficient and
      contradictory. Such a situation has at least partly arisen due to the inherent
      heterogeneity within the various clinical diagnostic categories. Syndrome sub
      categorization employing biological variables is suggested as a first step in
      order to achieve etiological homogeneity.

PMID- 8283200
TI  - A comparison of rat hippocampal mossy cells and CA3c pyramidal cells.
AB  - 1. There is a long-standing debate about whether the large spiny cells in the
      hilar region of the hippocampus should be classified as pyramidal cells of
      Ammon's horn or as a distinct cell type of the dentate gyrus. The rationale for
      grouping these hilar neurons (termed "mossy cells") with pyramidal cells of
      Ammon's horn is shared characteristics. In the present study we have compared the
      morphological and physiological characteristics of mossy cells and nearby CA3c
      pyramidal cells with the use of a rat hippocampal slice preparation. 2. Biocytin
      labeled neurons were examined on the basis of soma area, location, shape, number
      of primary dendrites, extent of dendritic spines, dendritic location, and axon
      trajectories. Mossy cells had larger soma areas than CA3c pyramidal cells, and
      they had more large complex spines (thorny excrescences) on their proximal
      dendrites and somata than CA3c pyramidal cells. Mossy cell dendritic trees and
      axon collaterals ramified in different regions of the hippocampus than dendrites
      and axons of CA3c pyramidal cells. 3. Intrinsic physiological properties, and
      spontaneous and evoked synaptic properties, were measured and compared. Mossy
      cells had significantly higher input resistances, smaller amplitude burst
      afterhyperpolarizations, smaller amplitude action potentials, less spike
      frequency adaptation, and more anomalous rectification than CA3c pyramidal cells.
      4. Mossy cells had spontaneous excitatory postsynaptic potentials (EPSPs) that
      were significantly higher in frequency and larger in amplitude than CA3c
      pyramidal cells. A larger proportion of mossy cells than CA3c pyramidal cells
      responded to perforant path stimulation with depolarizing postsynaptic potentials
      without any apparent hyperpolarization. Conversely, a smaller proportion of mossy
      cells than CA3c pyramidal cells responded to perforant path stimulation with
      inhibitory postsynaptic potentials (IPSPs), and spontaneous IPSPs were more
      difficult to detect in mossy cells. 5. The intrinsic physiological properties of
      mossy cells endow these cells with potent excitatory mechanisms but relatively
      fewer inhibitory control processes than CA3c pyramidal cells. Recordings of
      spontaneous and evoked PSPs suggest that mossy cells receive more excitatory
      input and less inhibitory input than CA3c pyramidal cells. These intrinsic and
      synaptic properties of mossy cells may explain this cell type's exceptional
      vulnerability to excitotoxic damage by intense afferent stimulation. 6. In
      summary, mossy cells were significantly different from CA3c pyramidal cells in
      many of their morphological, intrinsic physiological, and synaptic
      properties.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8283201
TI  - Average but not continuous speed match between motoneurons and muscle units of
      rat tibialis anterior.
AB  - 1. Properties of single motoneuron/muscle-unit combinations were determined for
      tibialis anterior (TA) in rats anesthetized with pentobarbital. The TA
      observations were systematically compared with those obtained earlier by the use
      of the same techniques from rat medial gastrocnemius (MG). 2. TA motoneurons were
      investigated with regard to afterhyperpolarization (AHP; total duration 32-74 ms,
      amplitude 0.39-4.96 mV) and axonal conduction velocity (41-79 m/s). TA muscle
      unit measurements included the time course of the isometric twitch (time-to-peak
      force 10.8-18.0 ms; total duration 42-92 ms), the maximum tetanic force (22-217
      mN), and a measure of fatigue sensitivity (fatigue index 5-100%). The range of
      twitch and AHP durations ("speed range") was markedly smaller in the present TA
      material than for MG. 3. The mean duration of the TA motoneuronal AHP (49 +/- 8
      ms, mean +/- SD) was close to that of its muscle-unit twitch (56 +/- 12 ms). Thus
      an "average" speed match existed between TA motoneurons and their muscle fibers.
      4. For TA there was no correlation between the time courses of AHP and twitch.
      Thus there was for TA no "continuous" speed match between the motoneurons and
      their muscle fibers. 5. For TA twitches or AHPs studied separately, there was a
      significant correlation between different time course measures. Furthermore,
      compared with TA units having relatively fast twitches, those with slower
      twitches tended to show 1) a smaller maximum tetanic force and 2) a greater AHP
      amplitude. Fatigue-resistant units tended to have slower twitches than fatigue
      sensitive ones.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283202
TI  - Late expiratory inhibition of stage 2 expiratory neurons in the cat--a correlate
      of expiratory termination.
AB  - 1. Intracellular recordings were made from stage 2 expiratory bulbospinal neurons
      (E2Ns) in the caudal part of the ventral respiratory group in pentobarbitone
      anesthetized cats, to characterize changes in neuronal input resistance (Rn) and
      synaptic inhibition occurring at the time of the expiratory-inspiratory phase
      transition of the respiratory cycle. 2. Rn was maximal between 30-90% of stage 2
      expiration, but decreased significantly during the last 10% of stage 2
      expiration. Mean normalized Rn for 60-90% of stage 2 expiration was 0.9 +/- 0.02,
      while mean Rn during the last 10% of stage 2 expiration was 0.68 +/- 0.09 (n =
      8). This decrease in Rn began 200-300 ms before rapid hyperpolarization of E2N
      membrane potential and onset of phrenic nerve activity. 3. Under conditions of
      strong central respiratory drive, constant injection of positive current into
      E2Ns sometimes revealed a transient membrane hyperpolarization that straddled the
      expiratory-inspiratory phase transition. During this transient event, Rn was
      markedly reduced. 4. Intracellular injection of Cl- or NO3- ions into E2Ns
      produced reversal of chloride-dependent inhibitory synaptic potentials (IPSPs).
      Comparison of averages of membrane potential pattern over the whole respiratory
      cycle during control conditions and IPSP reversal revealed several periods of
      synaptic inhibition: 1) weak but progressively increasing synaptic inhibition
      during the second half of stage 2 expiration, 2) strong transient synaptic
      inhibition beginning 200-300 ms before the onset of phrenic nerve activity and
      ending shortly after the onset of phrenic nerve activity, and 3) strong but
      progressively decreasing synaptic inhibition throughout inspiration.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8283203
TI  - Responses of single hamster parabrachial neurons to binary taste mixtures of
      citric acid with sucrose or NaCl.
AB  - 1. Although taste experience generally arises from a mixture of gustatory
      stimuli, most neurophysiological studies of the mammalian central gustatory
      system have focused on responses to single chemical stimuli. Recently, in a study
      of single third-order neurons in the hamster parabrachial nucleus (PbN), we
      reported that mixture suppression occurs in the responses to binary mixtures of
      sucrose and QHCl presented to the anterior tongue. Mixture suppression was
      reflected both in reduced response frequencies and in an altered pattern of
      responses across neurons. In the current report we extend our investigation of
      CNS neuron responses to binary mixtures of heterogeneous stimuli to include
      sucrose+citric acid mixtures and NaCl+citric acid mixtures. The response to each
      mixture was compared with the response to the more effective component (MEC)
      presented alone, and those that differed by more than a selected criterion (based
      on response variability) were identified. 2. For all mixture responses recorded,
      29% (79/256) involved mixture suppression (mixture response < MEC response), only
      6% (18/276) were greater than the response to MEC, and 65% (179/276) did not
      differ from the response to the MEC. 3. In Experiments 1 and 2, neurons were
      tested with four concentrations of sucrose or citric acid each presented alone
      and in binary mixtures with a single strong concentration of the other stimulus.
      Sucrose suppression (mixture response < sucrose response) occurred in 24% of
      mixture responses and was exhibited almost exclusively by sucrose-best neurons,
      primarily to the mixtures that contained the stronger sucrose and citric acid
      concentrations. Sucrose suppression involved a 40% reduction of mixture response
      frequencies compared with responses to the sucrose component alone. 4. In
      Experiments 3 and 4, neurons were tested with four concentrations of NaCl or
      citric acid each presented alone and in binary mixtures with a single strong
      concentration of the other stimulus. NaCl suppression (mixture response < NaCl
      response) occurred in 21% of mixture responses and was displayed by both sucrose
      best and NaCl-best neurons. NaCl suppression involved a 28% reduction in mixture
      response frequencies compared with responses to the NaCl component alone. In all
      experiments citric acid suppression (mixture response < citric acid response) was
      observed in only 6% of mixture responses and was relatively small in magnitude.
      5. The across-neuron patterns (ANPs) of taste responses, which are correlated
      with behavioral measures of taste similarity, were compared for mixtures and
      components.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8283204
TI  - Cholinergic and noradrenergic modulation of the slow (approximately 0.3 Hz)
      oscillation in neocortical cells.
AB  - 1. The pedunculopontine tegmental (PPT) cholinergic nucleus and the locus
      coeruleus (LC) noradrenergic nucleus were electrically stimulated to investigate
      their effects on the recently described slow oscillation (approximately 0.3 Hz)
      of neocortical neurons. Intracellular recordings of slowly oscillating, regular
      spiking and intrinsically bursting neurons from cortical association areas 5 and
      7 (n = 140) were performed in anesthetized cats. 2. Pulse trains to the PPT
      nucleus produced the blockage of rhythmic (approximately 0.3 Hz) depolarizing
      hyperpolarizing sequences in 79% of tested cortical neurons and transformed this
      slow cellular rhythm into tonic firing. The latency of the cortical cellular
      response to PPT stimulation was 1.2 +/- 0.5 (SE) s and its duration was 15.9 +/-
      1.9 s. The PPT-elicited suppression of the slow cellular oscillation was
      accompanied by an activation of the electroencephalogram (EEG) having a similar
      time course. Fast Fourier transform analyses of EEG activities before and after
      PPT stimulation showed that the PPT-evoked changes consisted of decreased power
      of slow rhythms (0-8 Hz) and increased power of fast rhythms (24-33 Hz); these
      changes were statistically significant. 3. The blockage of the slow cellular
      oscillation was mainly achieved through the diminution or suppression of the long
      lasting hyperpolarizations separating the rhythmic depolarizing envelopes. This
      effect was observed even when PPT pulse trains disrupted the oscillation without
      inducing overt depolarization and increased firing rate. The durations of the
      prolonged hyperpolarizations were measured during a 40-s window (20 s before and
      20 s after the PPT pulse train) and were found to decrease from 1.5 +/- 0.2 to
      0.7 +/- 0.1 s. The values of the product resulting from the duration (in
      seconds), the amplitude (in millivolts), and number of such hyperpolarizing
      events within 20-s periods were 51.5 +/- 5 and 5.1 +/- 1.9 before and after PPT
      stimulation, respectively. 4. The PPT effect was suppressed by systemic
      administration of a muscarinic antagonist, scopolamine, but not by mecamylamine,
      a nicotinic antagonist. 5. The PPT effect on cellular and EEG cortical slow
      oscillation survived, although its duration was reduced, in animals with kainate
      induced lesions of thalamic nuclei projecting to areas 5 and 7 (n = 3) as well as
      in animals with similar excitotoxic lesions leading to extensive neuronal loss in
      nucleus basalis (n = 2). These data indicate that the PPT effect is transmitted
      to neocortex through either thalamic or basal forebrain relays.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8283206
TI  - Cutaneous stimulation fails to alter motor unit recruitment in the decerebrate
      cat.
AB  - 1. An attempt was made to repeat the observation that cutaneous input to the cat
      medial gastrocnemius (MG) muscle sometimes had the differential effect of
      inhibiting motoneurons with slow axonal conduction velocity while simultaneously
      exciting others with fast conduction velocity. Dual microelectrode recording from
      intact ventral root filaments was used to study the effects of cutaneous inputs
      on recruitment order and on firing frequency of physiologically characterized MG
      motor units in decerebrate cats. Motor responses to pinch of the skin over the
      lateral surface of the ankle as well as electrical stimulation of the caudal
      cutaneous sural (CCS) nerve were contrasted with the responses to static muscle
      stretch as well as muscle vibration. 2. In contrast to the prediction,
      recruitment order in pairwise tests was the same for skin pinch or CCS
      stimulation as it was for MG stretch or vibration in all 32 tested pairs of motor
      units. This sample included seven pairs comprising one slow-twitch (S) and one
      fast-twitch motor unit, where the predicted reversal of recruitment should have
      been most apparent. Regardless of the source of excitation, recruitment of motor
      units of the MG was consistent with Henneman's size principle in approximately
      90% of trials. 3. Skin pinch increased the firing rate of 30 of 32 individual
      motor units previously activated by stretch or vibration, including 7 slow-twitch
      units. In the remaining two units, skin pinch transiently (100-400 ms) slowed the
      firing of an S unit in 11 of 13 vibration + pinch trials. The other unit (type
      unknown) showed one or two retarded spikes in each of four vibration + pinch
      trials. In three S units, including the lone inhibitable unit and two others that
      were only excited by skin pinch, there was a significant positive rank
      correlation between change in unit firing frequency and change in soleus
      integrated electromyographic activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8283205
TI  - In vitro electrophysiology of developing genioglossal motoneurons in the rat.
AB  - 1. Experiments were performed to determine the change in membrane properties of
      genioglossal (GG) motoneurons during development. Intracellular recordings were
      made in 127 GG motoneurons from rats postnatal ages 1-30 days. 2. The input
      resistance (R(in)) and the membrane time constant (t(aum)) decreased between 5-6
      and 13-15 days from 84.8 +/- 25.4 (SD) to 47.0 +/- 18.9 M omega (P < 0.01) and
      from 10.0 +/- 4.2 to 7.3 +/- 3.3 ms (P < 0.05), respectively. During this period,
      the rheobase (Irh) increased (P < 0.01) from 0.13 +/- 0.07 to 0.27 +/- 0.14 nA,
      and the percentage of cells exhibiting inward rectification increased from 5 to
      40%. Voltage threshold (Vthr) of the action potential remained unchanged
      postnatally. 3. There was also a postnatal change in the shape of the action
      potential. Specifically, between 1-2 and 5-6 days, there was a decrease (P <
      0.05) in the spike half-width from 2.23 +/- 0.53 to 1.45 +/- 0.44 ms, resulting,
      in part, from a steepening (P < 0.05) of the slope of the falling phase of the
      action potential from 21.6 +/- 10.1 to 32.9 +/- 13.1 mV/ms. The slope of the
      rising phase also increased significantly (P < 0.01) between 1-2 and 13-15 days
      from 68.4 +/- 31.0 to 91.4 +/- 44.3 mV/ms. 4. The average duration of the medium
      afterhyperpolarization (mAHPdur) decreased (P < 0.05) between 1-2 (193 +/- 53 ms)
      and 5-6 days (159 +/- 43 ms). Whereas the mAHPdur was found to be independent of
      membrane potential, there was a linear relationship between the membrane
      potential and the amplitude of the medium AHP (mAHPamp). From this latter
      relationship, a reversal potential for the mAHPamp was extrapolated to be -87 mV.
      No evidence for the existence of a slow AHP was found in these developing
      motoneurons. 5. All cells analyzed (n = 74) displayed adaptation during the first
      three spikes. The subsequent firing pattern was classified into two groups,
      adapting and nonadapting. Cells at birth were all adapting, whereas all cells but
      two from animals 13 days and older were nonadapting. At the intermediate age (5-6
      days), the minority (27%) was adapting and the majority (73%) was nonadapting. 6.
      The mean slope of primary range for the first interspike interval (1st ISI) was
      approximately 90 Hz/nA. This value was similar for both adapting and nonadapting
      cells and did not change postnatally.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8283207
TI  - Distribution of rubrospinal synaptic input to cat triceps surae motoneurons.
AB  - 1. We evoked steady-state synaptic potentials in triceps surae motoneurons of the
      cat by stimulating the hindlimb projection area of the contralateral
      magnocellular red nucleus at 200 Hz. We measured the effective synaptic currents
      (IN) underlying the synaptic potentials using a modified voltage-clamp technique.
      We also determined the effect of the rubrospinal input on the discharge rate of
      some of the motoneurons by inducing repetitive discharge with long injected
      current pulses during which the red nucleus stimulation was repeated. 2. At
      motoneuron resting potential, the distribution of IN from the red nucleus within
      the triceps surae pools was qualitatively similar to the distribution of synaptic
      potentials: 86% of the putative type F motoneurons received a net depolarizing IN
      from the red nucleus stimulation, whereas only 38% of the putative type S units
      did so. The mean values of IN were significantly different in the two groups
      [+4.1 +/- 5.0 nA (SD) for putative type F and -1.6 +/- 3.1 nA for putative type
      S]. 3. However, when the values of IN at threshold for repetitive firing were
      estimated, the distribution of IN from the red nucleus was quite different. At
      threshold, all of the putative type S units received hyperpolarizing IN but so
      did nearly half of the putative type F units. 4. As would be expected from the
      wide range of IN at threshold (-20 to +12 nA), the red nucleus input produced
      dramatically different effects on the discharge of different
      motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283208
TI  - Estrogen-sensitive neurons in the female rat ventral tegmental area: a dual route
      for the hormone action.
AB  - 1. Electrical stimulation of the ventral part of the midbrain central gray (CG)
      elicited antidromic action potentials in 136 neurons in the ventral tegmental
      area (VTA) of 23 urethan-anesthetized ovariectomized female rats. 2. Antidromic
      action potentials were positive-negative biphasic and completed mostly within 2.4
      ms. Many had a notch in their initial positive deflection, at which antidromic
      potentials often failed to propagate into the neuronal soma. 3. The latency for
      antidromic activation ranged 1.0-10.5 ms, and the threshold was 100-1,700 microA.
      The relative refractory period was 0.8-2.8 ms. In 23 neurons (17%) gradual
      changes in stimulus intensity caused latency jumps, suggesting that their axons
      terminate or spread into branches in stimulation sites. 4. The parameters for
      antidromic activation were compared among 12 animals with a subcutaneous Silastic
      capsule of estrogen and 11 others with a blank capsule. Estrogen raised the mean
      threshold from 675 +/- 40 (SE) microA (n = 69) to 908 +/- 40 microA (n = 67). At
      the same time, estrogen significantly decreased the probability of the antidromic
      propagation from 63 to 41%. No changes were detected in the latency or the
      refractory period. 5. The probability distribution of the threshold was different
      in ovariectomized animals from that in estrogen-treated animals. Estrogen
      increased the number of cells with thresholds in the 1,300- to 1,500-microA
      range. 6. The probability of antidromic propagation was stable in each neuron to
      stimuli repeated at 1.0 Hz. Electrical stimulation of the preoptic area (POA)
      with a 30-s train of 50-microA pulses at 100 Hz increased the probability of
      antidromic propagation into the soma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283209
TI  - Electrical properties of Y-79 cells, a multipotent line of human retinoblastoma.
AB  - 1. Whole-cell and perforated-patch tight-seal recording techniques were used to
      characterize the voltage-dependent membrane conductances of the Y-79 cells, a
      human retinoblastoma line composed of pluripotential retinal precursor cells. 2.
      Membrane resistance and capacitance were measured under current clamp, yielding
      approximate average values of 1.8 G omega and 26 pF, respectively. The cells are
      electrically excitable, and depolarization above -20 mV triggers slow action
      potentials. 3. Step depolarization of the membrane under voltage clamp elicits a
      high-threshold transient inward current, followed by a sustained, larger outward
      current. The outward current is carried by potassium ions, as determined by its
      susceptibility to blockage by K-channel antagonists [tetraethylammonium (TEA),
      Cs, and 4-aminopyridine (4-AP)] and insensitivity to reduction of external
      chloride concentration. 4. The isolated inward current displayed some unusual
      properties: its amplitude is directly related to extracellular calcium
      concentration, and replacement of calcium by magnesium completely abolishes it.
      However, none of the calcium channel antagonists tested (cadmium, nickel,
      nifedipine, and amiloride) exerted a substantial blockage. In addition, removal
      of external sodium or superfusion with tetrodotoxin significantly reduce the size
      of this current. 5. A single voltage-dependent conductance appears to underlie
      the inward current, because a variety of manipulations, such as changes in the
      holding potential, in the extracellular concentration of calcium or sodium, or
      superfusion with tetrodotoxin, failed to reveal the presence of kinetically
      distinct components. 6. The results suggest that a single voltage-dependent
      conductance mechanism underlies the depolarization-activated inward current in Y
      79 cells. This channel appears to be primarily permeable to calcium, but with a
      significant contribution by sodium ions. Its functioning appears to be modulated
      by extracellular calcium.

PMID- 8283210
TI  - Induction of voltage-dependent sodium channels by in vitro differentiation of
      human retinoblastoma cells.
AB  - 1. Neuronlike differentiation of Y-79 retinoblastoma was chemically induced in
      vitro, by plating the cells onto a poly-D-lysine and laminin substrate. The
      changes in voltage-dependent conductances after 48-72 h were examined with the
      whole-cell tight-seal and the perforated-patch recording techniques. 2. Although
      outward currents carried by potassium ions appeared qualitatively similar before
      and after differentiation, the depolarization-activated transient inward current
      displayed a pronounced acceleration of its activation and inactivation kinetics.
      3. After differentiation, both the threshold of activation and the steady-state
      inactivation curve of the inward current are displaced in the negative direction
      by approximately 10-20 mV as compared with untreated cells. The current attains
      its peak amplitude in approximately 1 ms at maximum activating voltages, and
      decays within 3 ms. In contrast, in undifferentiated cells these values are on
      the order of 6 and 60 ms, respectively. The time to recover from inactivation is
      also shortened 20-fold in differentiated cells. 4. Unlike the mixed conductance
      of undifferentiated cells, which requires extracellular calcium, the inward
      current of the neuronlike differentiated cells is insensitive to manipulations of
      external calcium. Instead, it can be completely abolished in a reversible way by
      sodium removal or by micromolar concentrations of tetrodotoxin (TTX) in the
      bathing solution. As such, it resembles in all salient respects the voltage
      dependent sodium conductance of nerve cells. 5. The fast sodium current expressed
      after neuronal differentiation is not the result of a progressive enhancement of
      an existing conductance, because no such component is discernible in
      undifferentiated cells. Moreover, recordings performed in cells at early stages
      of differentiation also failed to reveal the coexistence of the immature and the
      differentiated inward currents. 6. A possible account of the present observations
      is that the native inward current of undifferentiated Y-79 cells may correspond
      to a precursor form of the mature channel, and the observed developmental changes
      induced by chemical differentiation could be a consequence of progressive
      modification of the original channels, rather than expression of a separate class
      of proteins.

PMID- 8283211
TI  - Generation and transmission of respiratory oscillations in medullary slices: role
      of excitatory amino acids.
AB  - 1. The involvement of excitatory amino acid (EAA) receptors in the generation of
      respiratory rhythm and transmission of inspiratory drive to hypoglossal (XII)
      motoneurons was examined in an in vitro neonatal rat medullary slice preparation.
      Slices generated rhythmic inspiratory activity in XII nerves. The role of EAAs in
      rhythm generation was determined by analyzing perturbations of respiratory
      network activity after bath application of EAA receptor antagonists or local
      microinjection of antagonists into the main column of respiratory neurons in the
      ventrolateral medulla (ventral respiratory group), particularly in the pre
      Botzinger complex (pre-BotC). The involvement of EAAs in drive transmission to
      XII motoneurons was examined by recording perturbations in XII nerve discharge or
      motoneuron synaptic inputs after microinjection of EAA receptor antagonists into
      either the XII motor nuclei or sites in the ventrolateral medulla containing
      interneurons of the drive transmission circuit. 2. Block of non-N-methyl-D
      aspartate (non-NMDA) receptors by bath application of 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX) reversibly reduced XII nerve burst frequency and amplitude in a
      concentration-dependent manner, completely blocking respiratory motor output at
      concentrations > 4 microM. Activation of 2-amino-4-phosphonobutyric acid (AP-4)
      sensitive receptors with D,L AP-4 reduced XII nerve burst amplitude by 30% but
      did not alter burst frequency. Block of NMDA receptor channels by bath
      application of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10
      iminemaleate (MK-801) did not perturb the frequency or amplitude of motor output.
      Inhibition of EAA uptake in the slices by bath application of dihydrokainic acid
      reversibly increased the frequency and amplitude of XII motor discharge. 3. Block
      of non-NMDA receptors at multiple sites along the main column of respiratory
      neurons in the ventrolateral medulla, including the pre-BotC, by unilateral
      microinjection of CNQX produced a dose-dependent, bilateral reduction in XII
      nerve burst amplitude without substantial perturbations of the frequency of
      respiratory oscillations. Block of non-NMDA receptors within the pre-BotC at
      sites ventral to amplitude altering sites produced a reduction in frequency and
      ultimately bilateral block of respiratory network oscillations. 4. Non-NMDA
      receptor block within the XII motor nucleus by unilateral microinjection of CNQX
      produced a dose-dependent reduction in ipsilateral XII nerve discharge amplitude
      without perturbing the frequency of respiratory oscillations. Perturbations of
      contralateral XII nerve burst amplitude were significantly smaller. NMDA channel
      block within the XII motor nucleus did not affect inspiratory burst amplitude,
      whereas activation of AP-4 receptors caused a 30% reduction in amplitude.

PMID- 8283212
TI  - Monkey hippocampal neurons related to spatial and nonspatial functions.
AB  - 1. Neural activity in the monkey hippocampal formation (HF) was analyzed during a
      spatial moving task in which the monkey was guided by auditory and visual cues
      and when stimuli were presented from various directions. The monkey could control
      a motorized, movable device (cab) and its route to a target location by pressing
      the proper one of five available bars in an appropriate sequence (spatial moving
      task). In any of several locations in the field, neural responses were evident in
      relation to the presentation of various objects or human movement in some
      relative direction (left, anterior, right) as a directional stimulus test. 2. Of
      238 hippocampal neurons analyzed, 172 (72.3%, 238-66) responded in either the
      spatial moving task, or to the direction from which stimulation was presented, or
      to the location of the monkey in the field, or to some combination of these. 3.
      The activity of 79 (33.2%) neurons was higher when the monkey was in some
      specific location in the field during the spatial moving task, regardless of the
      approach route or other task parameters (place related neurons). 4. Responses to
      the task cues in the spatial moving task were evident in 110 (46.3%) neurons
      (task related neurons). Of these, 77 (32.4%) neurons were not place related. The
      remaining 33 (13.9%) neurons were both task related and place related. These
      neurons responded to task cues in only that part of the field in which place
      related responses occurred. The neural response to the task cues disappeared when
      the monkey moved out of the place response region. The place related and task
      related neural responses disappeared when the room light was switched off. Thus
      information from the environment outside of the cab contributed to the place
      related and task related responses. 5. Stimuli presented from certain specific
      directions induced responses, selectively, in 41 (17.2%) of the neurons
      (direction related neurons). The dependence of the preferred direction was
      described in one of three ways--egocentric, allocentric, or place-direction
      specific. Nineteen egocentric neurons responded to a stimulus only when it was
      presented from a certain direction relative to the orientation of the monkey,
      regardless of the location of the monkey. Eleven allocentric neurons responded to
      a stimulus only when it was presented at a particular position in the room,
      regardless of the location or orientation of the monkey.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8283213
TI  - Muscarinic receptor activation of potassium channels in rat dentate gyrus
      neurons.
AB  - 1. The effects of acetylcholine (ACh) on granule cells freshly dissociated from
      rat dentate gyrus (DG) were studied using the nystatin perforated patch
      technique. This method allowed us to study ACh-induced currents (IACh) under
      voltage clamp without "run-down" of the ACh response. In some experiments, we
      used the conventional whole-cell method for intracellular application of drugs
      not permeable to cell membrane. 2. At a holding potential of -40 mV, ACh induced
      an outward current. The amplitude of IACh increased in a sigmoidal fashion with
      increasing ACh concentration. The half-maximal response and the Hill coefficient
      determined from the relation between ACh concentration and response were 4.98 x
      10(-7) M and 1.70, respectively. 3. The reversal potential of IACh was close to
      the K+ equilibrium potential. The IACh was accompanied by an enhancement of the
      K+ current. 4. Muscarine and McN-A-343 mimicked the ACh response, whereas
      oxotremorine induced no response. 5. Muscarinic antagonists reversibly suppressed
      the IACh (10(-5) M) in a concentration-dependent manner, where the values of half
      inhibition concentration (IC50) were 1.03 x 10(-6) M for pirenzepine and 2.21 x
      10(-5) M for AF-DX-116. 6. Intracellular perfusion with GDP-beta S suppressed the
      IACh greatly. The IACh persisted in the neurons pretreated with an external
      solution containing pertussis toxin (IAP) for 18 h. 7. In the neurons perfused
      with Ca(2+)-free external solution containing 2 mM ethylene glycol-O,O'-bis (beta
      aminoethyl ether)-N,N,N',N'-tetraacetic acid and 10 mM Mg2+, the first
      application of ACh induced the IACh with an amplitude similar to that in the
      standard solution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283215
TI  - The role of brachial muscle spindle signals in assignment of visual direction.
AB  - 1. In the oculobrachial illusion, a target light attached to the unseen
      stationary hand is perceived as moving and changing spatial position when
      illusory motion of the forearm is elicited by brachial muscle vibration. Our goal
      was to see whether we could induce apparent motion and displacement of two
      retinally fixed targets in opposite directions by the use of oculobrachial
      illusions. 2. We vibrated both biceps brachii, generating illusory movements of
      the two forearms in opposite directions, and measured any associated changes in
      perceived distance between target lights on the unseen stationary hands. The
      stability of visual fixation of one of the targets was also measured. 3. The seen
      distance between the stationary targets increased significantly when vibration
      induced an illusory increase in felt distance between the hands, both with
      binocular and monocular viewing. 4. Subjects maintained fixation accuracy equally
      well during vibration-induced illusory increases in visual target separation and
      in a no-vibration control condition. Fixation errors were not correlated with the
      extent or direction of illusory visual separation. 5. These findings indicate
      that brachial muscle spindle signals can contribute to an independent
      representation of felt target location in head-centric coordinates that can be
      interrelated with a visual representation of target location generated by retinal
      and oculomotor signals. 6. A model of how these representations are interrelated
      is proposed, and its relation to other intersensory interactions is discussed.

PMID- 8283214
TI  - The rostral hypothalamus: an area for the integration of autonomic and sensory
      responsiveness.
AB  - 1. An investigation has been made of the effects of chemical stimulation of
      neurons in the rostral hypothalamus on cardiovascular and respiratory parameters
      and on a nociceptive viscerosomatic reflex (reflex activity recorded from a
      lumbar spinal nerve in response to electrical stimulation of visceral afferent
      fibers in the splanchnic nerve) in alphaxalone/alphadolone-anesthetised rats. 2.
      Neurons were stimulated by microinjection of DL-homocysteic acid (DLH) at
      ventromedial forebrain sites between 2 mm caudal and 3 mm rostral to bregma. Any
      changes were monitored in viscerosomatic reflex activity and in the rate and
      depth of respiration, arterial blood pressure, heart rate, and hindlimb muscle
      blood flow. 3. Viscero-somatic reflex activity was depressed to varying degrees
      after injection of DLH at 20/96 sites and this was always accompanied by some
      form of cardiovascular change. At 8 sites inhibition of the reflex was
      accompanied by a cardiovascular response that included an initial pressor
      response (type I response) and at the other 12 sites there was an initial
      depressor response (type II response). Injection of DLH at a further 30 sites
      evoked a depressor response and no change in viscerosomatic reflex activity and
      at the remaining 45 sites there was no detectable change in any of the variables
      measured. 4. The degree of inhibition evoked from type I sites (mean 90%) was
      significantly greater (P < 0.001) than that evoked from type II sites (mean 58%).
      Type I responses were only evoked from an extremely localized region in the
      rostral anterior hypothalamus that corresponds to the lateral area of the
      anterior hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8283216
TI  - Monosynaptic EPSPs in primate lumbar motoneurons.
AB  - 1. Homonymous and heteronymous monosynaptic composite excitatory postsynaptic
      potentials (EPSPs) were evaluated by intracellular recordings from 89 motoneurons
      innervating triceps surae (n = 59) and more distal (n = 30) muscles in 14
      pentobarbital-anesthetized monkeys (Macaca nemestrina). 2. Homonymous EPSPs were
      found in all motoneurons tested. The mean values +/- SD for maximum EPSP
      amplitude of triceps surae motoneurons were 2.5 +/- 1.3, 1.8 +/- 1.3 and 4.5 +/-
      2.0 mV for medial gastrocnemius, lateral gastrocnemius, and soleus motoneurons,
      respectively. Heteronymous EPSPs were almost always smaller than their
      corresponding homonymous EPSPs. 3. Triceps surae EPSP amplitude was larger in
      motoneurons with higher input resistance. However, this relationship was weak,
      suggesting that factors related to input resistance play a limited role in
      determining the magnitude of the EPSP. 4. The mean ratio +/- SD of the amplitude
      of the EPSP elicited by combined stimulation of all triceps surae nerves to the
      amplitude of the algebraic sum of the three individual EPSPs was 0.95 +/- 0.05.
      This ratio was greater in motoneurons with lower rheobase. 5. Some patterns of
      synaptic connectivity in the macaque are consistent with previously reported
      differences between primates and cat (e.g., heteronymous EPSPs elicited by medial
      gastrocnemius nerve stimulation in soleus motoneurons are small in macaque and
      other primates but large in cat). However, no overall pattern emerges from a
      comparison of the similarities and differences in EPSPs among species in which
      they have been studied (i.e., macaque, baboon, and cat). That is, there are no
      two species in which EPSP properties are consistently similar to each other, but
      different from those of the third species.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283217
TI  - Periodic synchronized bursting and intracellular calcium transients elicited by
      low magnesium in cultured cortical neurons.
AB  - 1. In Mg(2+)-free external solution, rat cortical neurons in cultured networks
      entered a stable firing mode, consisting of regular bursts of action potentials
      superimposed on long-lasting depolarizations. The average separation between
      bursts varied from culture to culture, but was usually between 5 and 20 s. The
      distribution of burst intervals followed a Gaussian or normal distribution, with
      a standard deviation of typically 10% of the average burst period. 2. A gradually
      depolarizing pacemaker potential was never observed between bursts, but the
      threshold for action potentials during the quiescent phase was > or = 10 mV above
      the resting potential. No progressive change in conductance or excitability was
      observed during the quiescent period. Intracellular stimulation of action
      potentials did not reproduce the long-lasting depolarization. 3. Switching from
      current clamp to voltage clamp at the resting potential revealed large
      postsynaptic currents, mainly excitatory but with a small inhibitory component,
      at the same phase and frequency as the spike bursts, showing that periodic
      synaptic input is responsible for the burst-depolarizations. The current could be
      eliminated by local application of 2-amino-5-phosphonovaleric acid (APV) or 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX) to the postsynaptic cell. In the
      presence of tetrodotoxin, irregular miniature excitatory postsynaptic currents
      were observed. 4. A fluorescent calcium indicator (fluo-3, 100 microM) was
      included in the whole-cell pipette solution, to allow simultaneous electrical and
      calcium measurements in the same cell. In current clamp, transient intracellular
      calcium increases were found, which were synchronized to the spike bursts. The
      Ca2+ rise lasted as long as the action potential burst, and was followed by an
      exponential decay considerably slower than that of the membrane potential.
      Calcium transients disappeared during voltage clamp at the resting potential,
      suggesting that calcium influx through voltage-dependent calcium channels greatly
      exceeds that through synaptic channels. 5. Multisite Ca2+ recording, after
      loading with fluo-3 acetoxymethyl (AM) ester, revealed that the onsets of burst
      related calcium transients were synchronized in all active cells of each view
      field, to within approximately 20 ms. Occasionally, secondary rhythms were
      observed in which only a subset of cells participated. The times to peak and the
      decay times of calcium transients varied among synchronized cells. 6. The
      pharmacology of the burst-related calcium transients was investigated by bath
      application of a variety of compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8283218
TI  - Single channel recordings of Nt- and L-type Ca2+ currents in rat neurohypophysial
      terminals.
AB  - 1. Ca2+ currents through single channels in acutely dissociated nerve terminals
      from rat neurohypophyses were recorded using cell-attached patch recordings with
      110 mM Ba2+ as the charge carrier. 2. One type (Nt, where the t denotes terminal)
      of single Ca2+ channel current was evoked only by depolarizing steps from holding
      potentials less negative than -50 mV. Because this channel opened primarily at
      the beginning of a 180-ms-long voltage pulse, the averaged ensemble current
      decayed rapidly (approximately 30 ms). Infrequently, the channel opened
      throughout such a long pulse, resulting in a long-lasting averaged ensemble
      current. The averaged channel open time constant (tau) was 0.34 ms and the two
      averaged closed time constants were 1.78 (tau 1) and 86.57 (tau 2) ms. The mean
      unitary slope conductance for this channel was 11 pS and its threshold for
      activation was approximately -10 mV. 3. The other type (L) of single Ca2+ channel
      current could be evoked in isolation by depolarizations from holding potentials
      more positive than or equal to -50 mV. This channel opened throughout an entire
      180-ms-long voltage pulse. The averaged ensemble current, therefore, showed
      little inactivation. The averaged channel open-time constant was 0.49 ms and the
      two average closed time constants were 2.02 (tau 1) and 79.91 (tau 2) ms. The
      mean unitary slope conductance for this channel was 25 pS. 4. Bay K 8644 (5
      microM), a dihydropyridine (DHP) Ca2+ channel agonist, increased the open
      probability of the larger-conductance L-type Ca2+ channel by prolonging the
      average duration (to 2.79 ms) of channel openings, but did not alter the single
      channel slope conductance. In contrast, the same concentration of Bay K 8644 did
      not affect the smaller-conductance Nt-type Ca2+ channel. The DHP Ca2+ channel
      antagonist nicardipine (5 microM), but not nifedipine (5 microM), reduced the
      open probability of the large-conductance L-type Ca2+ channel by shortening the
      duration (to 0.36 ms) of channel openings. 5. The voltage- and time-dependent
      properties of these two types of single Ca2+ channel currents are in close
      agreement with those of the two components of macroscopic Ca2+ currents
      previously reported using the "whole-terminal" recording method. Therefore these
      two types of single channels appear to underlie the macroscopic current. 6. Our
      studies suggest that the terminal Nt-type Ca2+ channel differs from the
      conventional somatic N- and T-type Ca2+ channels in some respects, and that the
      terminal L-type Ca2+ channel is similar to the conventional somatic L-type Ca2+
      channel.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8283219
TI  - Spatiotemporal firing patterns in the frontal cortex of behaving monkeys.
AB  - 1. Activity of up to 10 single units was recorded in parallel from frontal areas
      of behaving monkeys. 2. Spatiotemporal firing patterns were revealed by a method
      that detects all excessively repeating patterns regardless of their complexity or
      single-unit composition. 3. Excess of repeating patterns was found in 30-60% of
      the cases examined when timing jitter of 1-3 ms was allowed. 4. An independent
      test refuted the hypothesis that these patterns represented chance events. 5. In
      a given behavioral condition there were usually many different patterns, each
      repeating several times, and not one (or a few) pattern repeating many times. 6.
      In 13 out of 20 cases, when a single unit elevated its firing rate in association
      with an external event beyond 40/s, most of the spikes within that period were
      associated with excessively repeating spatiotemporal patterns. 7. Of 157 types of
      patterns whose excess was most marked, 107 were composed of spikes from one
      single unit, 45 of the patterns contained spikes from two single units, and only
      one was composed of spikes from three different single units. 8. These properties
      suggest that the patterns were generated by reverberations in a synfire mode
      within self-exciting cell assemblies.

PMID- 8283220
TI  - Brain stem modulation of spatial receptive field properties of single cells in
      the dorsal lateral geniculate nucleus of the cat.
AB  - 1. We studied the effect of electrical stimulation of the peribrachial region
      (PBR) in the brain stem on the visual response of single cells in the dorsal
      lateral geniculate nucleus (dLGN) to a light slit presented in a series of
      positions across the receptive field. The response was plotted against slit
      position, giving a spatial receptive field profile. 2. PBR stimulation markedly
      increased the visual response. In the middle of the receptive field center, the
      absolute response increase was considerably larger than in the peripheral parts
      of the receptive field or than the increase of spontaneous activity. The PBR
      stimulation also led to a small increase of the diameter of the receptive field
      center. 3. The maximum steepness of the receptive field profile for the dLGN
      cells increased by PBR stimulation. We suggest that the visual resolution in the
      dLGN cell is directly related to this maximal slope of the receptive field
      profile rather than to the width of the receptive field center. This would mean
      that increased input from the PBR, as presumably occurs during arousal, increases
      the visual resolution of the dLGN cells. 4. For some of the cells we could record
      S-potentials (slow potentials) in addition to action potentials. This allowed us
      to directly compared the receptive field center size of a dLGN cell with that of
      its retinal input. For these cells, the center size was considerably reduced by
      the geniculate relay. During PBR stimulation, the center size of these cells also
      increased slightly, but even in this condition it was reduced compared with the
      retinal input. The maximal slope of the receptive field profile in the dLGN cell
      during PBR stimulation was larger than for the retinal input. 5. We also examined
      the effect of ionophoretical application of acetylcholine (ACh) and bicuculline
      methchloride (BMC) on the spatial receptive field properties of dLGN cells. The
      effects of ACh were similar to those of PBR stimulation. Application of BMC, on
      the other hand, made the receptive field profile more similar to that of retinal
      ganglion cells.

PMID- 8283221
TI  - Basolateral membrane Cl- and K+ conductances of the dark-adapted chick retinal
      pigment epithelium.
AB  - 1. We characterized the basolateral membrane Cl- and K+ conductances of the dark
      adapted chick neural retina-retinal pigment epithelium (RPE)-choroid preparation.
      Conventional microelectrodes were used to measure apical (V(ap)) and basolateral
      (Vba) membrane voltage, and double-barreled Cl- and K+ selective microelectrodes
      were used to follow the time course and magnitude of ion concentration changes
      outside the basolateral (basal) membrane. 2. In response to a fivefold decrease
      in basal [Cl-]o, Vba rapidly depolarized by 6.4 +/- 0.7 (SE) mV, and the apparent
      resistance of the basolateral membrane (Rba) increased. The Cl- channel blocker
      4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) suppressed the Vba
      depolarization by 40% and blocked the Rba increase. Estimates of the relative Cl-
      conductance (transference number, TCl) from the DIDS-sensitive component of the
      Cl- diffusion potential gave an average value for TCl of 0.22 +/- 0.03. 3.
      Further evidence for a Cl- conductance was obtained by measuring changes in
      intracellular Cl- activity (aCli) induced by transtissue current. Depolarizing
      Vba elevated aiCl, whereas hyperpolarizing Vba had the opposite effect,
      consistent with conductive Cl- movement across the basal membrane. TCl estimated
      from these data averaged 0.23 +/- 0.02. 4. In response to a sixfold increase in
      basal [K+]o, Vba depolarized 6.1 +/- 0.8 mV. The amplitude of this K+ diffusion
      potential was inhibited 44 and 67% by 5 and 10 mM Ba2+, respectively. TK was
      estimated to be 0.61 +/- 0.05. 5. The rapid c-wave membrane hyperpolarizations in
      response to the light-evoked decrease in subretinal [K+]o were used to calculate
      the equivalent resistances of the apical membrane (R(ap)), basolateral membrane
      (Rba), and the paracellular shunt pathway (Rs). They were 152 +/- 10, 615 +/- 38,
      and 138 +/- 7 omega.cm2 (n = 11 tissues), respectively. From these data the
      equivalent electromotive force for the basal (Eba) and apical (Eap) membranes
      were estimated to be -45 +/- 2 and -77 +/- 1 mV, respectively. This estimate of
      Eba is in the range of that predicted from our estimates of TCl and TK,
      indicating that, in the dark-adapted chick retina, the resting conductance of the
      basal membrane can largely be accounted for by the Cl- and K+ conductances
      described here.

PMID- 8283222
TI  - Light-evoked modulation of basolateral membrane Cl- conductance in chick retinal
      pigment epithelium: the light peak and fast oscillation.
AB  - 1. We studied the ionic mechanism of the light-peak voltage of the DC
      electroretinogram (DC ERG) in an in vitro preparation of chick neural retina
      retinal pigment epithelium (RPE)-choroid. The light peak originates from a
      depolarization of the RPE basolateral (basal) membrane, associated with an
      increase in its conductance. Using conventional and Cl(-)-selective
      microelectrodes, we tested the hypothesis that the light-peak voltage is
      generated by an increase in Cl- conductance (gCl) of the basolateral (basal)
      membrane. 2. Perfusion of the RPE basal membrane with 4,4'-diisothiocyanostilbene
      2,2'-disulfonate (DIDS), a known blocker of gCl in chick RPE, suppressed both the
      light-peak depolarization and the accompanying conductance increase of the basal
      membrane. 3. Using sustained transepithelial current to clamp the basal membrane
      potential at different levels, we estimated the reversal potential of the light
      peak. At membrane potentials above the equilibrium potential for Cl- (ECl = -40
      +/- 10 mV mean +/- SE), light-peak polarity was reversed. Current-voltage (I-V)
      curves measured in the dark and at the peak of the light peak also gave a
      reversal potential in the same range as ECl. In addition, shifting ECl by
      changing intracellular Cl- (aCli) via passage of transepithelial current or
      perfusing the apical side of the RPE with the Cl- uptake blocker, furosemide,
      shifted the light-peak reversal potential in the same direction as the change in
      ECl. 4. The transference number for Cl-, TCl, was estimated from step decreases
      in basal Cl- and increased from 0.20 +/- 0.01 in the dark to 0.31 +/- 0.01 during
      the light peak. These results indicate an average increase of 55% in the relative
      conductance of the basal membrane for Cl-. 5. Light-evoked changes in aCli,
      measured with Cl(-)-selective microelectrodes, were too small to account for the
      change in basal membrane potential during the light peak. These data strongly
      support the hypothesis that the light peak originates from an increase in RPE
      basal membrane permeability to Cl-. 6. We also obtained support for the model of
      Joseph and Miller that the fast-oscillation trough of the DC ERG, generated by a
      delayed basal membrane hyperpolarization of the RPE, originates from light-evoked
      modulation of the Cl- transport pathway. Perfusing either the apical side of the
      RPE with furosemide or the basal side with DIDS suppressed the fast oscillation.
      The delayed basal hyperpolarization reversed polarity at membrane potentials
      positive to ECl.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8283223
TI  - Dopaminergic modulation of rod pathway signals does not affect the scotopic ERG
      of cat at dark-adapted threshold.
AB  - 1. Two rod-driven electroretinogram (ERG) components were recorded to monitor
      scotopic retinal signals during experimental manipulation of dopamine and gamma
      aminobutyric acid (GABA) in normal cat eyes and in eyes pretreated with 6
      hydroxydopamine (6-OHDA). The scotopic threshold response (STR) was elicited near
      absolute threshold to monitor signals traversing the rod pathway near quantal
      threshold; scotopic PII, which normally begins approximately 2 log units higher,
      was also monitored. Responses were evaluated by V-log I curves and criterion
      amplitudes after intravitreal drug injections into intact eyes in vivo. The
      depletion of dopaminergic cells by pretreating with 6-OHDA was confirmed
      histologically by immunocytochemical methods. 2. Dopamine abolished the STR and
      markedly decreased PII in the normal eye. Both 6-OHDA pretreatment and
      application of the dopamine antagonist, haloperidol, increased the STR
      amplitudes, but only for stimuli beginning 2 log units above threshold; PII
      amplitude also was increased. However, neither 6-OHDA pretreatment nor
      haloperidol affected the STR near absolute threshold. 3. Both GABA and
      bicuculline suppressed the STR in the normal eye. However, when applied to eyes
      pretreated with 6-OHDA or concurrent with haloperidol, bicuculline enhanced the
      STR. GABA enhanced the PII amplitude in the normal eye but had no effect in eyes
      pretreated with 6-OHDA or in the presence of haloperidol. 4. These results
      suggest that 1) dopaminergic activity modulates signals in the rod pathway at
      higher stimulus intensities but not near absolute threshold and 2) GABA can
      affect the scotopic PII component by acting through dopaminergic cells in the
      dark-adapted retina.

PMID- 8283224
TI  - Differential effects of cutaneous and deep application of inflammatory irritant
      on mechanoreceptive field properties of trigeminal brain stem nociceptive
      neurons.
AB  - 1. The aim of this study was to determine whether there are differential
      neuroplastic effects of cutaneous and deep stimuli on the mechanoreceptive field
      (RF) properties of nociceptive brain stem neurons recorded in trigeminal (V)
      subnucleus caudalis. 2. A total of 31 caudalis neurons were functionally
      identified in anesthetized rats as nociceptive neurons receiving convergent
      cutaneous and deep afferent inputs, and the effects of the small-fiber excitant
      and inflammatory irritant mustard oil applied to either tongue muscle or facial
      skin were tested on their cutaneous and deep RFs. 3. The expression of
      neuroplasticity on the cutaneous and deep RFs of the neurons was found to depend
      on the site of application of this irritant. Mustard oil injected into the tongue
      muscle produced a significant and reversible expansion of both the cutaneous and
      deep RFs. In contrast, application of mustard oil to facial skin resulted in a
      significant and reversible expansion of the cutaneous RF, but no deep RF
      expansion occurred. 4. These findings suggest that considerable functional
      neuroplasticity of the cutaneous and deep RF properties of V nociceptive neurons
      can be induced by a peripheral inflammatory irritant and that deep inputs are
      especially effective in evoking these neuroplastic changes.

PMID- 8283225
TI  - Synaptic transmission through cat lumbar ascending sensory pathways is suppressed
      during active sleep.
AB  - 1. Few data are available that describe the evoked activity of spinal cord
      sensory tract neurons as a function of behavioral state. Accordingly, experiments
      were performed in which ascending volleys were recorded extracellularly within
      the spinoreticular (SRT), spinothalamic (STT), and spinomesencephalic (SMT)
      tracts located in the ventrolateral reticular formation in response to low
      intensity electrical stimulation of the contralateral sciatic nerve in the
      chronic unanesthetized, behaving cat during naturally occurring episodes of
      wakefulness, quite sleep, and active sleep. 2. During episodes of wakefulness and
      quite sleep sciatic nerve stimulation produced a low-amplitude and long-duration
      orthodromic field potential that did not differ in amplitude or waveform.
      However, during the corresponding episode of active sleep, the sciatic nerve
      induced orthodromic field potential was markedly suppressed or abolished. 3. The
      effects of sustained microiontophoretic applications of inhibitory amino acid
      agonists, glycine, or gamma-aminobutyric acid during wakefulness or quite sleep
      markedly suppressed the antidromic field potential recorded from nearby VII
      motoneurons but did not alter the sciatic nerve-evoked orthodromic field
      potential, indicating that the sciatic response was recorded from ascending axons
      of passage emanating from lumbar spinal neurons. We suggest that lumbar neurons
      comprising the SRT, STT, and SMT tracts are subjected to a descending suppressor
      drive that is activated specifically during the behavioral state of active sleep.

PMID- 8283226
TI  - Dietary Na(+)-restriction prevents development of functional Na+ channels in
      taste cell apical membranes: proof by in vivo membrane voltage perturbation.
AB  - 1. Chorda tympani (CT) neural responses to NaCl were recorded while the potential
      across the apical membrane of taste cells was perturbed by voltage clamp in rats
      fed a Na(+)-restricted diet pre- and postnatally (Na(+)-restricted rats) and in
      controls. 2. Control rats gave CT responses that were enhanced at negative
      voltage clamp and suppressed at positive voltage clamp. In contrast, CT responses
      from Na(+)-restricted rats were virtually voltage insensitive. 3. Analysis of the
      voltage-sensitivity of the CT response shows that Na(+)-restricted rats have <
      10% of the density of functional apical Na+ channels normally present in control
      rats demonstrating that early dietary Na(+)-restriction prevents the functional
      expression of these key elements in salt taste transduction. Furthermore, the
      data demonstrate the value of this technique in assessing involvement of distinct
      cellular domains in taste transduction.

PMID- 8283227
TI  - Auditory spatial tuning of cortical neurons is sharpened in cats with early
      blindness.
AB  - 1. The specificity for the location of a sound source in azimuth was measured in
      single neurons of the anterior ectosylvian (AE) region of the cat's cortex, which
      includes the anterior auditory field (AAF) and the anterior ectosylvian auditory
      field (AEA). 2. The influence of visual experience on auditory spatial tuning of
      these neurons was determined by comparing responses in cats with binocular
      deprivation from birth with those in normal control cats. 3. Spatial tuning was
      measured under near free-field conditions by presenting broadband sounds through
      a speaker in seven different azimuthal locations, from -60 to +60 degree at 20
      degree intervals. Elevation was constant at the cats' ears. 4. In normal cats, a
      little over one-half of the neurons in the AE region (82/146 = 56%) showed some
      degree of azimuthal spatial tuning, as defined by at least a 2:1 ratio of
      responses between best and worst location. The rest (44%) were omnidirectional.
      5. In binocularly deprived cats, a significantly higher proportion (70/82 = 86%)
      of the neurons in the AE region were spatially tuned. Only 14% were
      omnidirectional. Median spatial tuning width was significantly sharper than in
      normal cats. 6. We conclude that visual deprivation from birth induces intermodal
      changes that enhance the response specificity of neurons in the auditory cortex.
      These modifications may constitute the neural basis of behavioral compensation
      for early blindness.

PMID- 8283228
TI  - 1G5: a calmodulin-binding, vesicle-associated, protein kinase-like protein
      enriched in forebrain neurites.
AB  - We have characterized cDNA clones of 1G5, an mRNA highly enriched in the
      mammalian forebrain that encodes a 504-residue protein found in association with
      perikaryal membranes and neurites. The protein, which accumulates predominantly
      postnatally, is associated with vesicles in both axons and dendrites. The
      sequence of the 1G5 protein highly resembles those of protein kinases with
      serine/threonine specificity; however, although most residues universally
      conserved among protein kinases are present, a few signature residues are absent
      from the 1G5 protein. Furthermore, although recombinant 1G5 protein binds
      calmodulin in the presence of calcium, it lacks kinase activity with a sample
      substrate.

PMID- 8283229
TI  - Molecular plasticity of adult Bergmann fibers is associated with radial migration
      of grafted Purkinje cells.
AB  - Embryonic Purkinje cells (PCs) from cerebellar primordia grafted in adult pcd
      mutant cerebellum replace missing PCs of the host, and become synaptically
      integrated into the defective cerebellar circuit. This process of neuronal
      replacement starts with the invasion of grafted PCs into the host cerebellum, and
      their radial migration through its molecular layer. The present study is aimed at
      determining whether the glial axes for this migration are embryonic radial glial
      cells that comigrate with the grafted PCs, or adult Bergmann fibers of the host,
      transiently reexpressing the molecular cues needed for their guidance of the
      migration. Transplants from a transgenic mouse line (Krox-20/lacZ14) in which
      Bergmann fibers could be identified by lacZ expression reveal that, despite the
      presence of X-gal-stained Bergmann fibers in the graft remnants and of grafted
      PCs in the host molecular layer, all Bergmann fibers in the host cerebellum lack
      of beta-galactosidase activity. Thus, these migratory axes belong to the host,
      not to the donor. Transplants from normal isogenic mouse embryos show that during
      the radial migration of grafted PCs (7 d after grafting) the involved host
      Bergmann fibers reexpress nestin (identified with monoclonal antibody Rat-401
      immunostaining), normally expressed only by immature Bergmann fibers. Five days
      later, when grafted PCs have arrested their migration, host Bergmann fibers again
      become Rat-401 negative. These results indicate that embryonic PCs can trigger in
      adult cerebellum the molecular changes necessary for their own migration and
      ultimate synaptic integration in the host cortical circuitry.

PMID- 8283230
TI  - Developmental expression of trkC, the neurotrophin-3 receptor, in the mammalian
      nervous system.
AB  - The mammalian trkC gene encodes a tyrosine protein kinase that serves as a
      functional receptor for neurotrophin-3 (NT-3). Here, we report that trkC is
      widely expressed in the developing and adult nervous system. Using in situ
      hybridization, we first detect trkC transcripts in the telencephalon and spinal
      cord of embryonic day 9.5 mouse embryos. In later embryonic development, trkC is
      expressed in various structures of the CNS including the caudatoputamen, septal
      nuclei, cerebellum, and brainstem. In the PNS, trkC hybridization appears to
      correlate, both temporally and spatially, with the outgrowth of axons toward
      their peripheral targets. trkC transcripts were also identified in the autonomous
      enteric nervous system as well as in some non-neural tissues such as the wall of
      the aorta and the acini of the submaxillary and sublingual glands. In the adult
      mouse, trkC gene expression is heterogeneously distributed throughout the brain,
      with highest levels in limbic and diencephalic structures. These results indicate
      that the trkC gene is widely expressed in the three identified branches of the
      mammalian nervous system and appears to correlate with the expression of NT-3,
      its cognate ligand. The apparent colocalization of trkC transcripts with NT-3
      raises the possibility this neurotrophin exerts its trophic effects by a
      paracrine and/or autocrine mechanism.

PMID- 8283231
TI  - Analysis of the feeding motor pattern in the pond snail, Lymnaea stagnalis:
      photoinactivation of axonally stained pattern-generating interneurons.
AB  - We have photoinactivated identified feeding interneurons known as N1 and N2
      neurons. These are pattern-generating neurons that are active in the protraction
      of the radula and rasping phases, respectively, of the feeding cycle of the pond
      snail. The N1 or N2 feeding interneurons in the buccal ganglia were filled with
      the fluorescent dye 5(6)-carboxyfluorescein (5-CF) from the cut end of the nerve
      that contains their axon. Filling the cerebrobuccal connective (N = 151) stained
      just one N1 cell in the contralateral buccal ganglion. Filling the postbuccal
      nerve stained neurons symmetrically in both buccal ganglia (N = 75): only one
      labeled cell in each ganglion is an N2 interneuron. The feeding rhythm was evoked
      by depolarizing a modulatory neuron, the SO, located in the buccal ganglia. The
      axonally filled N1 interneuron was irradiated at its axon in the buccal
      commissure with blue laser light (intensity of 0.5 MW.m-2). Irradiation of just
      one N1 completely blocked the feeding rhythm (seven preparations). In seven
      further preparations, N1 ablation slowed the SO-driven feeding rhythm and
      weakened the N1 input to the feeding neurons. Irradiation of the cell bodies of
      both the filled left and right N2 interneurons killed the cells but did not
      produce any consistent change in the feeding rate (15 preparations). The feeding
      interneurons and motoneurons still showed the characteristic N2 phase synaptic
      inputs, so more, as yet unidentified, N2 neurons must be located in other parts
      of the buccal ganglia. We conclude that the participation of the identified N1
      interneurons is essential for the normal feeding pattern while other, still to be
      identified N2 neurons must be present and must contribute to the feeding rhythm.
      We suggest that the extra redundancy of the N2 network may be related to the
      greater necessity of sensory feedback control during rasping than during
      protraction of the radula.

PMID- 8283232
TI  - Basal forebrain lesions in monkeys disrupt attention but not learning and memory.
AB  - Cognitive impairments in humans and animals have been linked to dysfunction of
      neurons in the basal forebrain cholinergic system (BFCS). Degeneration of these
      cells may be, in part, responsible for some of the cognitive deficits observed in
      Alzheimer's disease (AD). Although memory deficits are associated with lesions of
      the BFCS in rats, impairments in memory have been more subtle following similar
      lesions in monkeys. To evaluate the effects of BFCS lesions on cognitive
      processes in monkeys, we have systematically investigated the behavioral effects
      of ibotenic acid injections in the medial septum, nucleus of the diagonal band of
      Broca, and nucleus basalis of Meynert in cynomolgus monkeys, using a large series
      of cognitive tasks that examined different mnemonic and attentional abilities.
      These lesions did not impair accuracy in delayed nonmatching-to-sample, delayed
      response, simple or concurrent visual discriminations, spatial discriminations,
      or discrimination reversals. However, these lesions disrupted attentional
      focusing. Similar impairments in attention have been noted in patients with AD.
      BFCS lesions increased sensitivity to injections of the cholinergic antagonist
      scopolamine in a delayed nonmatching-to-sample task, indicating that the central
      cholinergic system was compromised in these monkeys. In concert, the results of
      this study suggest that the primate basal forebrain may be more involved in
      attentional than mnemonic processes, and that degeneration of neurons in the BFCS
      in cases of AD may contribute to the attention deficits observed in these
      individuals.

PMID- 8283233
TI  - Olfactory glomeruli in the zebrafish form an invariant pattern and are
      identifiable across animals.
AB  - Glomeruli are anatomical and possibly functional modules in the vertebrate
      olfactory bulb. We investigated the spatial arrangement of glomeruli in the
      olfactory bulbs of adult zebrafish (Brachydanio rerio). A solution of the
      lipophilic tracer Dil was injected into the nasal cavities. Axons of sensory
      neurons projecting from the olfactory epithelium into the bulb were traced
      anterogradely, thus labeling the whole population of glomeruli. The glomerular
      distribution was analyzed in detail by confocal laser-scanning microscopy. We
      find that a typical olfactory bulb contains a small number of about 80 glomeruli
      that have a stereotyped configuration in all animals investigated. All glomeruli
      exhibit bilateral symmetry. Twenty-two single glomeruli could be identified from
      animal to animal by their characteristic position and morphology. The remaining
      glomeruli either are embedded in glomerular plexus and therefore cannot be
      delineated reliably, or belong to a densely clustered subpopulation of on average
      49 glomeruli in the dorsal olfactory bulb. No sexually dimorphic glomeruli were
      identified. To test whether glomerular constancy is specific for the zebrafish,
      we performed similar tracing experiments in the goldfish and found several
      indications for a similar invariance of glomeruli in this species. The remarkable
      stereotypy of this pattern is reminiscent of the insect olfactory system and has
      been demonstrated here for the first time in a vertebrate. It will now be
      possible to examine whether these identifiable glomeruli are functionally
      specialized in terms of odor processing. If so, zebrafish may emerge as a
      tractable model system for studies on olfactory coding.

PMID- 8283234
TI  - Segmental patterning of rat and chicken sympathetic preganglionic neurons:
      correlation between soma position and axon projection pathway.
AB  - The segmental organization of midthoracic rat and chicken sympathetic
      preganglionic neurons was examined by retrograde labeling in vivo and in vitro.
      The results demonstrate that individual sympathetic preganglionic neurons project
      only rostrally or caudally within the sympathetic chain, even though the spinal
      segment in which they reside provides innervation to both rostral and caudal
      ganglia. In addition, there is both a segmental and an intrasegmental pattern in
      the thoracic sympathetic column, in which the position of preganglionic neurons
      is related to the direction they project in the sympathetic chain. Thoracic
      sympathetic preganglionic neurons are organized into discrete segmental units,
      each of which exhibits an internal rostrocaudal polarity with respect to the
      direction of axon projection in the sympathetic chain. The rostrocaudal bias of
      this internal polarity is graded from segment to segment along the longitudinal
      axis. Since there is minimal overlap between thoracic segments, the transition
      from one segment to another entails a sharp change in the pathway choice of the
      preganglionic neurons. The organization of the preganglionic projections thus
      includes (1) segmental periodicity, (2) intrasegmental gradients of neuronal
      identity, and (3) an axial gradient of segment identity. The significance of
      these findings is twofold. First, they suggest a functional organization that may
      be related to the specificity of sympathetic reflex action. Second, they reveal a
      cellular organization that suggests an underlying segmental pattern in the
      developing spinal cord.

PMID- 8283235
TI  - A presynaptic gain control mechanism among sensory neurons of a locust leg
      proprioceptor.
AB  - The chordotonal organ at the femorotibial joint of a locust hind leg monitors
      extension and flexion movements of the tibia. During evoked or imposed movements
      of this joint the central terminals of afferent neurons from the chordotonal
      organ receive depolarizing, inhibitory synaptic inputs. The afferent spikes are
      therefore superimposed on these depolarizing IPSPs, which are generated
      indirectly by other afferents from the same organ that respond to the same
      movement. Each afferent spikes preferentially to particular features of a joint
      movement, and its synaptic input is typically greatest at the joint position or
      during the movement that generates its best response. Afferents that respond to
      only one direction of movement receive synaptic inputs either during movements in
      both directions, or only during movements in their preferred direction. Phasic
      velocity-sensitive afferents receive either phasic inputs during movements, or
      tonic inputs at new sustained joint positions, or both. The spikes of tonic
      position-sensitive afferents are superimposed on synaptic inputs that are
      dependent on joint position. The synaptic inputs sum but do not themselves evoke
      antidromic spikes in the afferent terminals. They reduce the amplitude of
      orthodromic afferent spikes by 12-28%, and this is accompanied by a reduction of
      up to 50% in the amplitude of monosynaptic EPSPs evoked by an afferent in
      postsynaptic leg motor neurons. These interactions suggest that a local gain
      control mechanism operates between the afferents of this proprioceptor. Thus, the
      effectiveness of the output synapses of an individual afferent is regulated by
      the network action of other chordotonal afferents that respond to the same
      movement.

PMID- 8283236
TI  - GABA-induced chemokinesis and NGF-induced chemotaxis of embryonic spinal cord
      neurons.
AB  - During CNS development, neuroblasts proliferate within germinal zones of the
      neuroepithelium, and then migrate to their final positions. Although many neurons
      are thought to migrate along processes of radial glial fibers, increasing
      evidence suggests environmental factors also influence nerve cell movement.
      Extracellular matrix molecules are thought to be involved in guiding neuronal
      migration, and molecules such as NGF and GABA exert trophic effects on immature
      neurons. The nature of the signals that initiate and direct neuroblast migration,
      however, is unknown. In vitro, NGF and GABA promote neurite outgrowth from
      cultured cells, and NGF induces axonal chemotaxis (directed migration along a
      chemical gradient). At earlier developmental stages, these molecules could
      influence neuroblast movement. Therefore, we investigated whether these molecules
      induce embryonic neuronal migration. Using an in vitro microchemotaxis assay, we
      show that rat embryonic spinal cord neurons migrate toward picomolar NGF and
      femtomolar GABA beginning at embryonic day 13 (E13). Cells exhibit chemotactic
      responses to NGF while GABA stimulates chemokinesis (increased random movement).
      GABA effects are mimicked by muscimol and inhibited by bicuculline and
      picrotoxin, suggesting GABA motility signals are mediated by GABA receptor
      proteins. Expression of GABA receptors by embryonic cord cells has been
      previously reported (Mandler et al., 1990; Walton et al., 1993). We used
      polymerase chain reaction analysis to demonstrate the presence of NGF and trk
      mRNA in E13 and E14 cord cells, indicating the cells express message for both NGF
      and high-affinity NGF receptors. Immunohistochemistry of E13 spinal cord sections
      indicates that NGF and GABA colocalize in fibers close to the target destinations
      of migrating neurons, suggesting diffusible gradients of these molecules provide
      chemoattractant signals to migratory cells. Thus, in vitro, neuroblast migration
      is induced by specific signaling molecules that are present in the developing
      spinal cord, and may stimulate migration of embryonic neurons prior to
      synaptogenesis.

PMID- 8283237
TI  - Increased deafferentation-induced cell death in chick brainstem auditory neurons
      following blockade of mitochondrial protein synthesis with chloramphenicol.
AB  - Second-order auditory neurons in nucleus magnocellularis (NM) of the chick
      brainstem undergo a series of rapid metabolic changes following unilateral
      cochlea removal, culminating in the death of 25% of NM neurons. Within hours of
      cochlea removal, ipsilateral NM neurons show marked increases in histochemical
      staining for the mitochondrial enzymes succinate dehydrogenase and cytochrome
      oxidase (CO). We have shown previously in an ultrastructural study that these
      increases in oxidative capacity are mediated in part by a rapid increase in
      mitochondrial volume within deafferented neurons. In neurons that are destined to
      die as a result of deafferentation, mitochondria are smaller, stain poorly for
      CO, and often contain vacuoles associated with oxidative dysfunction. Our present
      set of experiments is designed to test the hypothesis that increases in oxidative
      metabolism are necessary for NM neuronal survival following removal of afferent
      input. We used chloramphenicol (CAP), a mitochondrial protein synthesis
      inhibitor, to block the characteristic increase in CO activity and mitochondrial
      proliferation following cochlea removal. We then studied the effects of CAP on NM
      neuronal survival following deafferentation. When CAP was administered
      continuously at 600 mg/kg/d for 5 d following cochlea removal, deafferentation
      induced neuronal death in NM was significantly increased from 22% to 36%. Higher
      dose (1200 mg/kg/d) pulses of CAP were administered for the first 6, 12, or 24 hr
      following cochlea removal. After 5 d survival, greater increases in neuronal cell
      death were found in animals treated for the first 12 or 24 hr (65% neuronal
      death). CAP administration for the first 6 hr had no significant effect on
      neuronal survival. The effects of CAP on neuronal cell death in NM are not likely
      to be due to systemic effects of the drug, but instead to a specific change in
      mitochondrial function. Our results suggest that enhanced oxidative enzyme
      function plays an important role in the survival of NM neurons during the first
      24 hr after deafferentation. The nature of the signal(s) eliciting mitochondrial
      enhancement and the means by which it influences NM survival are not known.

PMID- 8283238
TI  - Differential distribution of the synapsins in the rat olfactory bulb.
AB  - The distribution of the different forms of synapsin in the rat olfactory bulb was
      investigated by biochemical and immunocytochemical methods. Western blots of
      tissue derived from microdissection of the surface and core regions of the
      olfactory bulb were performed using antibodies to synapsin I and synapsin II. The
      relative levels of the synapsins in the core region of the olfactory bulb were
      similar to the cerebral cortex. In contrast, the surface region of the olfactory
      bulb had significantly higher levels of synapsin IIa and significantly lower
      levels of synapsin I, relative to the cortex. Immunocytochemical localization of
      synapsin I and synapsin II revealed that synapsin I immunoreactivity was the most
      dense in the external plexiform layer and in the glomeruli; immunoreactivity was
      also present in the granule cell layer and the periglomerular regions. Synapsin
      II immunoreactivity was the most dense in the glomeruli. The external plexiform
      layer, internal plexiform layer, and granule cell layer exhibited much lower
      immunoreactivity. To determine the source of synapsin II immunoreactivity in the
      glomeruli, the olfactory epithelium was damaged to decrease the primary afferent
      input to the bulb. Three to four days later, olfactory bulb sections were double
      labeled with anti-olfactory marker protein (OMP) antibodies and anti-synapsin II
      antibodies. Following denervation, both OMP and synapsin II immunoreactivities
      were diminished, and continued to colocalize in regions retaining
      immunoreactivity. Individual puncta were immunoreactive for both OMP and synapsin
      II. Occasional puncta contained only synapsin II immunoreactivity. These results
      indicate that the distribution of the synapsins in the olfactory bulb differs
      from most other brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283239
TI  - Microtubule polarity in the peripheral processes of trigeminal ganglion cells:
      relevance for the retrograde transport of herpes simplex virus.
AB  - The directional movement of many cellular organelles in neurons is dependent on
      polarized microtubules and direction-specific motor molecules. Microtubules are
      also thought to mediate the retrograde transport of herpes simplex virus (HSV) in
      sensory neurons. To define the cellular machinery responsible for retrograde
      axonal transport of HSV, we have investigated the polarity of microtubules in the
      peripheral axons of trigeminal ganglion neurons. The long ciliary nerves of
      rabbits were prepared for a standard "hook assay" of microtubule polarity. Axons
      in cross-sectioned nerves contained microtubules with almost uniform orientation.
      The fast-growing, plus ends of these axonal microtubules are located distal to
      the cell body and the slow-growing, minus ends are directed centrally. To
      determine the role played by microtubules in the retrograde transport of HSV in
      these axons, we injected the retrobulbar space of mice with the microtubule
      inhibiting drugs colchicine, vinblastine, or nocodazole or with the microfilament
      inhibitor cytochalasin D and 1 d later inoculated the cornea with HSV. We found
      that colchicine, vinblastine, or nocodazole reduced by 52-87% the amount of virus
      recovered from the ganglion 3 d postinoculation, compared to vehicle-treated
      animals. In contrast, cytochalasin D or beta-lumicolchicine did not significantly
      reduce the amount of HSV recovered from the ganglion. We conclude that the
      retrograde axonal transport of HSV from axon endings in the cornea to the
      trigeminal ganglion cell bodies requires intact microtubules and occurs in a plus
      to-minus direction on the microtubules. Our data are consistent with the
      hypothesis that the retrograde axonal transport of HSV is mediated by a minus end
      directed motor molecule, for example, cytoplasmic dynein.

PMID- 8283240
TI  - Effects of prolonged darkness on light responsiveness and spectral sensitivity of
      cone horizontal cells in carp retina in vivo.
AB  - Light responses of cone- and rod-driven horizontal cells were recorded
      intracellularly from opened eyes of intact, immobilized carp and the effects of
      prolonged darkness on these cells were examined. When the retina was left in the
      dark, responses of cone horizontal cells to a moderate test flash presented once
      every 10 min gradually and steadily decreased in size (dark suppression effect).
      Following a repetitive presentation of the test flash, the light responsiveness
      of the cells was enhanced. In contrast, the rod horizontal cells did not show the
      dark suppression effect and the light responsiveness of these cells increased in
      the dark. Effects of prolonged darkness on the spectral sensitivity of L-type and
      R/G-type cone horizontal cells were also studied. The spectral sensitivity of L
      type cells, determined just after background illumination was extinguished,
      agreed reasonably well with that of red-sensitive (R-) cones, but it matched
      better that of green-sensitive (G-) cones when determined in prolonged darkness.
      We further show that depolarizing responses of R/G-type cone horizontal cells to
      long-wavelength flashes, driven by R-cones, were abolished after prolonged
      darkness. Taken together, these results suggest that input from R-cones
      converging onto the cone horizontal cells is more significantly suppressed after
      prolonged dark adaptation than input from G-cones. Due to the suppression of the
      R-cone input, enhancement of responses of the L-type cone horizontal cells to
      long-wavelength stimulation in the presence of a green background light was no
      longer seen after prolonged darkness.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283241
TI  - Overlapping and distinct actions of the neurotrophins BDNF, NT-3, and NT-4/5 on
      cultured dopaminergic and GABAergic neurons of the ventral mesencephalon.
AB  - The neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT
      3), and neurotrophin-4/5 (NT-4/5) were compared for their effects in promoting
      the survival and/or regulation of expression of phenotypic markers of
      dopaminergic and GABAergic neurons in cultures derived from embryonic rat ventral
      mesencephalon. Dopaminergic neuron number and phenotypic expression were
      monitored by tyrosine hydroxylase (TH) immunocytochemistry, and measurement of
      high-affinity dopamine uptake activity and dopamine content, respectively. High
      affinity GABA uptake, glutamic acid decarboxylase (GAD) activity, and endogenous
      GABA content were used to detect GABAergic neurons. Seven days of treatment with
      either BDNF or NT-3 resulted in dose-dependent increases in the number of TH
      positive neurons, with maximal responses of 3-fold and 2.3-fold, respectively.
      Dopamine uptake activity and dopamine content were similarly increased. The
      effects of BDNF and NT-3 on dopamine uptake activity showed no additivity. NT-4/5
      treatment elicited the greatest increase (7-fold) in the number of TH-positive
      neurons, as well as a 2.6-fold increase in dopamine content. In marked contrast
      to BDNF or NT-3, NT-4/5 had no effect on dopamine uptake capacity. BDNF, NT-3, or
      NT-4/5 also produced dose-dependent elevations of 2-3-fold in GABA uptake
      activity. These effects were not additive. GAD activity was increased by BDNF
      (1.8-fold) and NT-3 (threefold) treatment, but not by NT-4/5, whereas GABA
      content was increased to a similar extent by all three neurotrophins. NGF had no
      effect on any of the parameters measured in this study. Northern analyses
      indicated that the mRNAs encoding TrkB and TrkC, the functional high-affinity
      receptors for BDNF and NT-4/5, and NT-3, respectively, are expressed in the
      substantia nigra of adult rat brain, as well as in cultures of developing ventral
      mesencephalon. Taken together, our results indicate that BDNF and NT-3 have
      broadly similar effects in promoting the survival and differentiated phenotype of
      both dopaminergic and GABAergic neurons of the developing substantia nigra.
      Although BDNF and NT-4/5 are thought to act through the same high-affinity
      receptor, TrkB, it is evident that these two neurotrophins have distinct as well
      as overlapping actions toward mesencephalic dopaminergic or GABAergic neurons.

PMID- 8283243
TI  - Fate of myelin lipids during degeneration and regeneration of peripheral nerve:
      an autoradiographic study.
AB  - Four weeks after labeling myelin lipids with an intraneural injection of 3H
      acetate, sciatic nerves were crushed, and the distribution of radiolabeled myelin
      lipids was followed by autoradiography from 1 d to 10 weeks later. Just prior to
      crush, silver grains were localized to the myelin sheath. Three days after crush,
      axons were degenerating and myelin sheaths were breaking down; silver grains
      appeared over lipid droplets within Schwann cells, fibroblasts, and macrophages.
      One week after crush the basal-lamina-delimited Schwann-cell tubes (Bungner
      bands) contained myelin debris, and some tubes already contained regenerating
      axons. Schwann cells were often displaced to the periphery of the tubes by
      phagocytes containing heavily labeled myelin debris; extratubal macrophages
      within the endoneurium contained labeled lipid droplets but no myelin debris. Two
      weeks after nerve crush silver grains were associated with newly formed myelin
      around regenerating axons. Many extratubal endoneurial macrophages now contained
      labeled myelin debris and lipid droplets. By 3 weeks myelination of regenerating
      axons was advanced, and the myelin sheaths were well labeled. Extratubal
      macrophages had become the major labeled structure within the nerve because they
      contained large amounts of labeled myelin debris and lipid droplets. From 4 to 10
      weeks after nerve crush the new myelin sheaths continued to thicken and to be
      well labeled. Debris-laden extratubal macrophages remained the major site of
      labeled material within the endoneurium. Our results confirm that there is
      reutilization of myelin cholesterol by Schwann cells to form new myelin, and
      indicate that some lipid catabolism takes place in Schwann cells and endoneurial
      fibroblasts prior to infiltration of the nerve by macrophages. However, most of
      the myelin debris is phagocytized by macrophages within 1-2 weeks following nerve
      injury. These debris-laden macrophages persist within the nerve for many weeks,
      indicating that much of the salvaged cholesterol is not reutilized for myelin
      regeneration.

PMID- 8283242
TI  - Mitochondria buffer physiological calcium loads in cultured rat dorsal root
      ganglion neurons.
AB  - We sought to determine whether low-affinity, high-capacity mitochondrial Ca2+
      uptake contributes to buffering physiological Ca2+ loads in sensory neurons.
      Intracellular free calcium concentration ([Ca2+]i) and intracellular free
      hydrogen ion concentration ([H+]i) were measured in single rat dorsal root
      ganglion (DRG) neurons grown in primary culture using indo-1 and carboxy-SNARF
      based dual emission microfluorimetry. Field potential stimulation evoked action
      potential-mediated increases in [Ca2+]. Brief trains of action potentials
      elicited [Ca2+]i transients that recovered to basal levels by a single
      exponential process. Trains of > 25 action potentials elicited larger increases
      in [Ca2+]i, recovery from which consisted of three distinct phases. During a
      rapid initial phase [Ca2+]i decreased to a plateau level (450-550 nM). The
      plateau was followed by a slow return to basal [Ca2+]i [Ca2+]i transients
      elicited by 40-50 action potentials in the presence of the mitochondrial
      uncoupler carbonyl cyanide chlorophenyl hydrazone (CCCP), or the electron
      transport inhibitor antimycin A1, lacked the plateau, and the recovery to basal
      [Ca2+]i consisted of a single slow phase. Depolarization with 50 mM K+ produced a
      multiphasic [Ca2+]i transient and increased [H+]i from 74 +/- 3 to 107 +/- 8 nM.
      The rise in [H+]i was dependent upon extracellular Ca2+ and was inhibited by
      mitochondrial poisons. With mitochondrial Ca2+ buffering pharmacologically
      blocked, the recovery to basal [Ca2+]i was unaffected by removal of extracellular
      Na+. We conclude that large Ca2+ loads are initially buffered by fast
      mitochondrial sequestration that effectively uncouples electron transport from
      ATP synthesis, leading to an increase in [H+]i. Small Ca2+ loads are buffered by
      a nonmitochondrial, Na(+)-independent process.

PMID- 8283244
TI  - Pairing-specific, activity-dependent presynaptic facilitation at Aplysia sensory
      motor neuron synapses in isolated cell culture.
AB  - Synapses made by Aplysia sensory neurons onto motor- and interneuron followers in
      the intact nervous system exhibit an associative form of synaptic facilitation
      that is thought to contribute to classical conditioning of the animal's gill and
      siphon withdrawal reflex (Hawkins et al., 1983; Walters and Byrne, 1983). Here we
      demonstrate that a similar associative facilitation can be induced between
      individual sensory and motor neurons isolated in culture. Pairing tetanic
      stimulation with either of two facilitatory transmitters, 5-HT or small
      cardioactive peptide, considerably prolongs facilitation compared to either
      tetanus or transmitter alone. When corrected for the depression that occurs
      simply in response to low-frequency testing, the facilitation produced by one
      pairing trial does not decay for more than 20 min after training. This
      facilitation requires the temporal pairing (0.5 sec forward interstimulus
      interval) of the two stimuli, tetanus and 5-HT. Delivering the same two stimuli
      in an unpaired fashion (1 min forward interval) fails to produce the long-lasting
      effect. Measurements of spontaneous transmitter release during either paired or
      unpaired training reveal no changes in unitary mEPSP or mEPSC ("mini") amplitude,
      indicating that the facilitation involves a presynaptic mechanism. While both
      forms of training dramatically increase the initial frequency of spontaneous
      release, mini frequency does not remain elevated as long as the evoked EPSP
      following paired training, nor does paired training specifically enhance
      spontaneous release frequency. Pairing-specific facilitation was not blocked by
      the protein kinase C inhibitor H7. In contrast, the same training procedure
      produced pairing-specific increases of sensory neuron excitability and action
      potential width, suggesting that cAMP-mediated processes are involved in the
      paired effect. Although Ca2+ influx is necessary for the associative effect
      (Abrams, 1985), we find that the facilitation does not require influx through L
      type voltage-gated Ca2+ channels, since the effect was not blocked by the
      dihydropyridine antagonist nitrendipine. Together, these findings indicate that
      the mechanism underlying associative, activity-dependent facilitation is
      intrinsic to the sensory neuron synapse, that it is presynaptically mediated by
      processes unique to evoked synaptic transmission, and that it appears to involve
      a pairing-specific broadening of the presynaptic action potential, allowing
      enhanced Ca2+ influx through the dihydropyridine-insensitive channels responsible
      for release.

PMID- 8283245
TI  - Cytoskeletal movements and substrate interactions during initiation of neurite
      outgrowth by sympathetic neurons in vitro.
AB  - The initial outgrowth of neurites from chick sympathetic neurons grown in vitro
      was investigated by time-lapse microscopy with laser-scanning and conventional
      light microscopes. Video-enhanced contrast, differential interference contrast
      optics (VECDIC) were used to monitor movements of neuronal cytoplasm, as well as
      the movements of small beads attached to the surface membrane, and interference
      reflection microscopy (IRM) was used to determine the concomitant pattern of
      attachment to the growth substrate (polyornithine or laminin). Related changes in
      the distributions of actin filaments, microtubules, and neurofilaments were
      determined by fluorescence labeling methods. Neurite formation on both substrates
      entailed invasion of the actin cores of filopodia by cytoplasm containing
      microtubules and neurofilaments. Small beads attached to the surface membrane
      surrounding the cytoplasm moved outward simultaneously with the cytoplasm.
      Cytoplasm invaded filopodia of neurons plated on laminin soon after attachment to
      the substrate or, for neurons generated in vitro, within as little as 3 min after
      cytokinesis. However, cytoplasm invaded filopodia of neurons grown on
      polyornithine only when they contacted a three-dimensional object such as another
      cell or a large, polyornithine-coated polystyrene bead. The observation that
      adhesion of filopodia to polyornithine-coated beads can initiate neurite
      formation is inconsistent with the commonly held view that neurite formation
      requires adhesion mediated by specific cell adhesion molecules. Simultaneous IRM
      and DIC imaging showed that cytoplasm invaded filopodia when only their tips were
      closely apposed to a substrate but not when they were closely apposed to a
      substrate along their entire lengths. These findings help to elucidate the
      mechanisms by which interactions between the cytoskeleton and the growth
      substrate initiate and produce the neuronal movements that lead to the formation
      of neurites.

PMID- 8283246
TI  - Aggregation of vasopressin mRNA in a subset of axonal swellings of the median
      eminence and posterior pituitary: light and electron microscopic evidence.
AB  - The mRNA encoding vasopressin has recently been documented within the
      magnocellular hypothalamo-neurohypophyseal projections of the rat such as the
      median eminence (ME) and the posterior pituitary (PP), suggesting the possibility
      of its axonal transport. To address the origin of this mRNA and to investigate
      the functional significance of this unexpected axonal transport of mRNA, we have
      examined its subcellular localization within both magnocellular perikarya and
      their axonal projections. For this purpose, we have used nonradioactive in situ
      hybridization techniques in order to localize the vasopressin mRNA with precision
      at the ultrastructural level in magnocellular perikarya, dendrites, and axons
      from control, salt-loaded, and lactating rats. This approach permitted us to
      demonstrate directly the axonal localization of vasopressin mRNA. Moreover, we
      were able to obtain novel information concerning vasopressin mRNA
      compartmentation within both perikarya and axons. At both light and electron
      microscopic levels, we observed vasopressin mRNA-containing cells in the
      hypothalamic magnocellular cell body groups, but not in the ME or in the PP. When
      vasopressin mRNA was detected in medium-size dendrites, it was always associated
      with the rough endoplasmic reticulum (RER). Within the labeled magnocellular
      perikarya, the abundant vasopressin mRNA was mainly associated with discrete
      areas of the RER. However, vasopressin mRNA was never detected in the Golgi
      apparatus or in association with neurosecretory granules, in perikarya or axons.
      These data suggest that vasopressin mRNA translation is restricted to certain
      segments within the RER, and that axonal transport of vasopressin mRNA does not
      involve the classical neurosecretory pathway, via the Golgi apparatus and the
      neurosecretory granules, as has been proposed. Within the magnocellular neuron
      axons, vasopressin mRNA could be detected only in a subset of axonal swellings,
      all of which were confined to the internal layer of the ME and the PP. The mRNA
      containing swellings were numerous in 7 d salt-loaded animals, less abundant in
      lactating animals, and almost undetectable in control animals. In all groups of
      animals, no vasopressin mRNA was detectable in any other region of the
      magnocellular neuron axons, including undilated axonal segments or varicose
      swellings. These results strongly suggest that, under physiological activation
      such as chronic salt loading, axonal vasopressin mRNA is increased and becomes
      aggregated in a selected subset of swellings of the ME and the PP. Furthermore,
      these data indicate that along the magnocellular neuron axons, the swellings may
      differ in their biochemical and functional features. Further analysis focused on
      the mRNA-accumulating swellings may illuminate the function of RNA within the
      axonal compartment.

PMID- 8283247
TI  - Novel hyperpolarization-activated K+ current mediates anomalous rectification in
      crayfish muscle.
AB  - The ionic current underlying anomalous rectification in opener muscle fibers of
      crayfish was studied under two-electrode voltage clamp. Opener muscle fibers
      showed a mean resting potential (RP) of -64.8 mV and an input resistance of 0.4 M
      omega. Hyperpolarizing voltage command pulses from a holding potential (H) of -60
      mV evoked an instantaneous voltage-independent linear current (IL) followed by a
      time- and voltage-dependent inward current (IAB) that reached a steady state
      within 500 msec. The reversal potential of IAB (EAB) was estimated from tail
      current amplitudes. At an extracellular K+ concentration ([K+]o) of 5.4 mm the
      mean EAB was -61.8 mV. EAB shifted toward positive potentials by 50.8 mV for a 10
      fold increase in [K+]o. The conductance underlying IAB (GAB) increased
      sigmoidally with hyperpolarization, starting close to the RP, saturating at a
      GAB,max of about -140 mV, and showing a mean half-activation at -94.4 mV. The
      activation curve of GAB shifted 53.6 mV toward positive potentials with a 10-fold
      increase in [K+]o. GAB,max did not increase in raised [K+]o. The activation and
      deactivation kinetics of IAB were accurately described by single exponentials
      with similar time constants (< 100 msec). Time constants changed as an
      exponential function of the membrane potential. IAB, its time course, GAB, and
      EAB were not modified in the following conditions: (1) Na(+)- and Ca(2+)-free
      solutions, (2) intracellular EGTA, (3) extracellular (100 mM) or intracellular
      tetraethylammonium, (4) extracellular Cs+ (up to 50 mM), Rb+ (up to 10 mM), Ba2+
      (13.5 mM), or Mn2+ (13.5 mM). However, low extracellular concentrations of Cd2+
      or Zn2+ strongly and reversibly reduced both IL and IAB. Therefore, we conclude
      that anomalous rectification in crayfish muscle is generated by a voltage- and
      time-dependent K+ current IAB. This current displayed many electrophysiological
      and pharmacological characteristics that distinguished it from all others
      mediating anomalous rectification described previously.

PMID- 8283248
TI  - A model for the development of simple cell receptive fields and the ordered
      arrangement of orientation columns through activity-dependent competition between
      ON- and OFF-center inputs.
AB  - Neurons in the primary visual cortex of higher mammals respond selectively to
      light/dark borders of a particular orientation. The receptive fields of simple
      cells, a type of orientation-selective cell, consist of adjacent, oriented
      regions alternately receiving ON-center and OFF-center excitatory input. I show
      that this segregation of inputs within receptive fields can occur through an
      activity-dependent competition between ON-center and OFF-center inputs, just as
      segregation of inputs between different postsynaptic cells into ocular dominance
      columns appears to occur through activity-dependent competition between left-eye
      and right-eye inputs. These different outcomes are proposed to result, not from
      different mechanisms, but from different spatial structures of the correlations
      in neural activity among the competing inputs in each case. Simple cells result
      if ON-center inputs are best correlated with other ON-center inputs, and OFF with
      OFF, at small retinotopic separations, but ON-center inputs are best correlated
      with OFF-center inputs at larger separations. This hypothesis leads robustly to
      development of simple cell receptive fields selective for orientation and spatial
      frequency, and to the continuous and periodic arrangement of preferred
      orientation across the cortex. Input correlations determine the mean preferred
      spatial frequency and degree of orientation selectivity. Estimates of these
      correlations based on measurements in adult cat retina (Mastronarde, 1983a,b)
      produce quantitative predictions for the mean preferred spatial frequencies of
      cat simple cells across eccentricities that agree with experiments (Movshon et
      al., 1978b). Intracortical interactions are the primary determinant of cortical
      organization. Simple cell spatial phases can play a key role in this
      organization, so arrangements of spatial phases and preferred orientations may
      need to be studied together to understand either alone. Possible origins for
      other cortical features including spatial frequency clusters, afferent ON/OFF
      segregation, blobs, pinwheels, and opponent inhibition within simple cell
      receptive fields are suggested. A number of strong experimental tests of the
      hypothesis are proposed.

PMID- 8283249
TI  - Different kinetics govern dopaminergic transmission in the amygdala, prefrontal
      cortex, and striatum: an in vivo voltammetric study.
AB  - The regulation of extracellular dopamine (DA) concentrations was examined and
      compared in vivo in four projection fields of mesotelencephalic dopaminergic
      neurons with fast-scan cyclic voltammetry at carbon-fiber microelectrodes.
      Transient electrical stimulation of ascending DA fibers in a near physiological
      range of frequencies (10-20 Hz) elicited similar levels of extracellular DA in
      the medial prefrontal cortex (MPFC), basal lateral amygdaloid nucleus (BAN),
      caudate-putamen (CP), and nucleus accumbens (NAc) despite the documented 90-fold
      disparity in DA tissue levels and terminal density. However, marked differences
      were observed in the dynamics and overall frequency dependence of the evoked
      synaptic overflow of DA. These differences are due to the significantly different
      rates of release and uptake found in each of the four regions. For example, rate
      constants for the release of the four regions. For example, rate constants for
      the release and uptake of DA were similar in the MPFC and BAN but approximately 8
      and 50 times less, respectively, than that in the CP and NAc. When the parameters
      were normalized to endogenous DA tissue content, a unique picture emerged:
      compared to all other regions, relative release was 10-fold greater in the MPFC
      while relative uptake was at least 10 times less in the BAN. The results further
      differentiate the functional characteristics of mesotelencephalic dopaminergic
      systems and demonstrate the regiospecific nature of DA neural transmission in the
      brain. In addition, the regulation of extracellular DA levels in the MPFC and BAN
      is suitable for the "long-range" transfer of chemical information in the brain
      and is consistent with a hypothesis of extrasynaptic neurotransmission.

PMID- 8283250
TI  - A quantitative measure for short-term cortical plasticity in human vision.
AB  - The human visual system is normally very good at determining the relative
      positions of objects in space, but under certain conditions contextual influences
      can cause significant errors in this process. We studied spatial localization
      around an artificial scotoma, a small mask that occludes part of the visual field
      while a dynamic pattern is shown over a surrounding region, and found that the
      ability to determine the position of short line segments was strongly biased
      toward the interior of the scotoma. We attribute this "shift" or misassignment of
      position to receptive field (RF) expansions within the artificial scotoma as seen
      in recent physiological studies. Furthermore, our findings show that this shift
      begins within 1 sec of stimulus presentation, suggesting that RFs are constantly
      altered by their local context and that these dynamics are a part of normal
      vision.

PMID- 8283251
TI  - Tuning of MST neurons to spiral motions.
AB  - Cells in the dorsal division of the medial superior temporal area (MSTd) have
      large receptive fields and respond to expansion/contraction, rotation, and
      translation motions. These same motions are generated as we move through the
      environment, leading investigators to suggest that area MSTd analyzes the optical
      flow. One influential idea suggests that navigation is achieved by decomposing
      the optical flow into the separate and discrete channels mentioned above, that
      is, expansion/contraction, rotation, and translation. We directly tested whether
      MSTd neurons perform such a decomposition by examining whether there are cells
      that are preferentially tuned to intermediate spiral motions, which combine both
      expansion/contraction and rotation components. The finding that many cells in
      MSTd are preferentially selective for spiral motions indicates that this simple
      three-channel decomposition hypothesis for MSTd does not appear to be correct.
      Instead, there is a continuum of patterns to which MSTd cells are selective. In
      addition, we find that MSTd cells maintain their selectivity when stimuli are
      moved to different locations in their large receptive fields. This position
      invariance indicates that MSTd cells selective for expansion cannot give precise
      information about the retinal location of the focus of expansion. Thus,
      individual MSTd neurons cannot code, in a precise fashion, the direction of
      heading by using the location of the focus of expansion. The only way this
      navigational information could be accurately derived from MSTd is through the use
      of a coarse, population encoding. Positional invariance and selectivity for a
      wide array of stimuli suggest that MSTd neurons encode patterns of motion per se,
      regardless of whether these motions are generated by moving objects or by motion
      induced by observer locomotion.

PMID- 8283252
TI  - Memory through metamorphosis in normal and mutant Drosophila.
AB  - To establish that a stable, long-lasting form of memory exists in Drosophila, we
      trained third-instar larvae by electroshocking them in the presence of a specific
      odor using a Pavlovian conditioning procedure. We show that conditioned odor
      avoidance produced in larvae still was present in adults 8 d later. Such memory
      through metamorphosis was specific to the temporal pairing of odor and shock;
      presentations of odors alone or shock alone did not produce a change. Thus, the
      memory involved associative processes. We also show that similar training of the
      single-gene memory mutants dunce and amnesiac did not yield any detectable
      learning in larvae or memory retention in adults, suggesting that these mutations
      interfere with long-term memory (LTM) formation even if LTM is induced
      independently of earlier memory retention processes.

PMID- 8283253
TI  - Death of developing septal cholinergic neurons following NGF withdrawal in vitro:
      protection by protein synthesis inhibition.
AB  - Fetal septal neurons were grown in vitro under glass coverslips. This sandwich
      culture method significantly increased general neuronal survival, reduced glial
      proliferation, and permitted the removal of serum from the growth medium after 5
      d in vitro. Thereafter, a simple, and completely defined, medium was used, and
      the effects of NGF, NGF withdrawal, and protein synthesis inhibition were
      examined on septal cholinergic neurons. NGF added to septal cultures at the time
      of plating resulted in a threefold increase in the number of cholinergic neurons
      seen at 14 d in vitro but had no effect on the survival of non-cholinergic cells.
      Cholinergic neurons identified by staining for AChE, ChAT, and p75NGFR could be
      maintained in serum-free, NGF-supplemented medium for over 40 d. When NGF was
      removed and NGF antibodies added to 14-d-old cultures, less than 30% of
      cholinergic neurons survived a further 4 d, but when NGF was similarly withdrawn
      from 35-d-old cultures, over 75% of cholinergic neurons survived. Reapplication
      of NGF after 3 but not after 12 or more hours of NGF withdrawal from 14-d-old
      cultures prevented the death of most cholinergic neurons. When NGF was withdrawn
      from 14-d-old cultures in the presence of the protein synthesis inhibitor
      cycloheximide, over 75% of the cholinergic neurons survived. These findings
      suggest that septal cholinergic neurons are dependent on NGF for survival only
      during a critical period of development and that growth factor-regulated
      developmental cell death may occur in CNS neurons by activation of programmed
      cell death requiring protein synthesis.

PMID- 8283254
TI  - Contemporary management of meningiomas: radiation therapy as an adjuvant and
      radiosurgery as an alternative to surgical removal?

PMID- 8283255
TI  - Meningiomas: a quest for the optimum therapy.

PMID- 8283256
TI  - Postoperative irradiation for subtotally resected meningiomas. A retrospective
      analysis of 140 patients treated from 1967 to 1990.
AB  - The authors retrospectively analyzed 140 patients treated at the University of
      California, San Francisco, from 1967 to 1990 to evaluate the results of radiation
      therapy (median 5400 cGy) given as an adjuvant to subtotal resection of
      intracranial meningioma. Of the 140 meningiomas, 117 were benign and 23 were
      malignant. The median follow-up period was 40 months. The overall survival rate
      at 5 years was 85% for the benign and 58% for the malignant tumor groups (p =
      0.02); the 5-year progression-free survival rates were 89% and 48%, respectively
      (p = 0.001). For patients with benign meningioma, the 10-year overall and
      progression-free survival rates were 77%. An improved progression-free survival
      rate in that group was not related to tumor size but was associated with a
      younger age (p = 0.01) and treatment after 1980 with innovative technologies (p =
      0.002); none of those variables affected the progression-free survival rate in
      the patients with malignant meningioma. Increased progression-free survival in
      the benign tumor group was also significantly associated with increasing the
      minimum radiation dose (p = 0.04). The 5-year progression-free survival rate for
      patients with benign meningioma treated after 1980 (when computerized tomography
      or magnetic resonance imaging was used for planning therapy) was 98%, as compared
      with 77% for patients treated before 1980 (p = 0.002). There were no second
      central nervous system tumors. Morbidity (3.6%) included sudden blindness or
      cerebral necrosis and death. When total resection of benign meningioma is not
      feasible, subtotal resection combined with precise treatment planning techniques
      and adjuvant radiation therapy can achieve results comparable to those of total
      resection.

PMID- 8283257
TI  - Recurrent spheno-orbital meningioma.
AB  - A series of 15 patients who underwent neurosurgical procedures for recurrent
      spheno-orbital meningioma is reported. There were 11 women and four men, with a
      mean age of 46 years. The mean duration between the first and second operations
      was 46 months. Progressive proptosis without neurological deficit was the most
      common symptom. All tumors were large at the time of reoperation and involved the
      greater and lesser wings of the sphenoid bone and the orbit. Aggressive resection
      in all patients resulted in no deaths and only slight morbidity, with the
      exception of one patient who developed blindness 24 hours after surgery due to
      central retinal artery occlusion. Fourteen patients were improved cosmetically
      and one patient, treated early in the series, had persistent proptosis due to
      inadequate bone removal. No attempt was made to remove tumor within the cavernous
      sinus in patients who were neurologically normal. Although postoperative imaging
      demonstrated complete gross excision of tumor in nine patients, 10 underwent
      conventional radiation therapy for residual tumor visualized at the time of
      surgery in the dura of the superior orbital fissure, the cavernous sinus, or the
      basal optic canal. Although this study is inconclusive and requires further long
      term documentation, no recurrences have been seen to date in the follow-up
      period, ranging from 16 to 95 months. The following important points are
      discussed: 1) the failure by experienced surgeons to radically excise bone,
      tumor, and involved dura at the first operation; 2) the importance of early
      aggressive therapy, depending upon the patient's age and medical condition; 3)
      the almost invariable intracranial dural involvement, which at times was seen
      only by gadolinium-enhanced magnetic resonance imaging and not visualized on
      computerized tomography; 4) an illustrated stepwise surgical technique for
      complete resection through a small craniotomy without the need for complicated
      reconstruction of the orbit or temporal fossa; 5) the role of radiation therapy
      when removal is incomplete or deemed hazardous because of cavernous sinus
      involvement; and 6) the excellent cosmetic results possible with minimal
      morbidity and no mortality.

PMID- 8283258
TI  - Pituitary adenomas in childhood and adolescence. Results of transsphenoidal
      surgery.
AB  - Pituitary adenomas are uncommon in childhood. Between 1975 and 1988, 36 patients
      underwent transsphenoidal resection at the Mayo Clinic before their 17th
      birthday. Fifteen (41.7%) had prolactin (PRL)-secreting tumors, 16 (44.4%) had
      adrenocorticotropic hormone (ACTH)-secreting tumors (including two patients with
      Nelson-Salassa syndrome), and three (8.3%) had tumors secreting growth hormone
      (GH); two patients (5.6%) had clinically nonfunctioning tumors. Of the 36
      patients, 21 (58.3%) were girls, and girls predominated in every group except
      that with ACTH-secreting tumors, where they accounted for only 37.5% of the
      patients. The average age at the time of surgery was 14.7 +/- 2.2 years, the
      youngest patient being 7.3 years old. The ACTH-secreting tumors were associated
      with an earlier onset of symptoms than the other tumor types: six (37.5%) of 16
      patients became symptomatic before 10 years of age, compared with two (10.0%) of
      the 20 other patients. Presenting symptoms primarily reflected endocrine
      dysfunction, with neurological presentation (visual field deficits) occurring in
      only two patients. There were no deaths in this patient group. Significant
      operative morbidity included steroid-induced psychosis in one patient and
      diabetes insipidus in three, which resolved in two. Plurihormonal tumors, broadly
      defined as tumors producing more than one hormone, were common, comprising five
      (36%) of 14 PRL-secreting tumors, all three GH-secreting tumors, and one of two
      clinically nonfunctioning tumors, or 25.7% overall. Macroadenomas accounted for
      89% of plurihormonal tumors. Long-term follow-up review (median > 5 years)
      revealed good control of PRL-secreting tumors (although five of 15 patients had
      received postoperative radiotherapy), contrasted with a 25% late recurrence rate
      for ACTH-secreting tumors, which had an 80% initial remission rate. The majority
      of patients had good endocrine function, including reproductive function. It is
      concluded that: 1) although pediatric pituitary adenomas occur primarily in
      adolescence, Cushing's disease is found at any age; 2) transsphenoidal surgery is
      feasible and safe in this age group; 3) plurihormonal tumors occur more
      frequently in the pediatric age group than in adults; and 4) long-term control
      rates in PRL- and ACTH-secreting tumors are probably similar to those seen in
      adults.

PMID- 8283259
TI  - The incidence and treatment of asymptomatic, unruptured cerebral aneurysms.
AB  - The importance of early detection by various radiological techniques of
      asymptomatic, unruptured aneurysms as a means of preventing subarachnoid
      hemorrhage (SAH) is discussed in this report. Four hundred volunteers underwent
      clinical and radiological evaluations between March, 1988, and September, 1992.
      Studies included a neurological examination as well as digital subtraction
      cerebral angiography via a femoral arterial catheter, computerized tomography, T1
      and T2-weighted magnetic resonance (MR) imaging of the whole brain, and MR
      angiography. The evaluation revealed 27 asymptomatic, unruptured intracranial
      aneurysms in 26 volunteers, for an incidence of 6.5%. The subjects ranged in age
      from 39 to 71 years, with an average of 55 years. The aneurysms were located on
      the internal carotid artery in 13 cases (48%), the anterior communicating artery
      in six (22%), the middle cerebral artery in six (22%), and the basilar artery in
      two (7%). Aneurysms ranged in size from 5 mm or less in 16 cases, 6 to 10 mm in
      nine, and 11 to 15 mm in one; one aneurysm was more than 15 mm, with a maximum
      diameter of 2 cm. Volunteers with a family history of SAH within the second
      degree of consanguinity showed a higher incidence of aneurysms (17.9%). Aneurysm
      clipping was performed on 20 of the 26 cases with no significant morbidity or
      mortality. These findings support the contention that aggressive early detection
      of unruptured aneurysms may improve the outcome in patients harboring cerebral
      aneurysms by preventing the devastating effects of SAH.

PMID- 8283260
TI  - Severe symptomatic vasospasm: the role of immediate postoperative angioplasty.
AB  - The clinical success of angioplasty for symptomatic vasospasm following
      subarachnoid hemorrhage (SAH) depends on early intervention and can best be
      achieved after the aneurysm is occluded. However, patients presenting with
      unsecured ruptured aneurysms and established clinical vasospasm offer a dilemma
      for the surgeon. The authors describe the cases of five such patients who
      underwent acute clipping of aneurysms followed by immediate postoperative
      angioplasty between 1988 and 1992. All were referred at least 5 days after SAH.
      Severe vasospasm compatible with the clinical presentation was confirmed by
      angiography. The patients met the department's criteria for angioplasty but,
      because of unclipped aneurysms, were first taken patients met the department's
      criteria for angioplasty but, because of unclipped aneurysms, were first taken to
      the operating room for a craniotomy and aneurysm obliteration. Angiography was
      repeated immediately after surgery. Arterial narrowing had progressed during
      surgery in two patients. In all patients, postoperative mechanical dilatation was
      achieved with the use of a silicone microballoon. Following angioplasty,
      transcranial Doppler ultrasound flow velocities and single-photon emission
      computerized tomography evaluation indicated improved cerebral perfusion compared
      to preoperative determinations. Four patients improved clinically and made a good
      recovery. In this subgroup of patients presenting with proven symptomatic
      vasospasm and an unclipped but ruptured aneurysm, urgent surgical obliteration of
      the aneurysm followed by immediate postoperative angioplasty may be a safe and
      reasonable means to improve outcome.

PMID- 8283261
TI  - Direct clipping of basilar trunk aneurysms using temporary balloon occlusion.
AB  - In the surgical treatment of basilar trunk aneurysms, there is still considerable
      technical difficulty in gaining both proximal artery control and a sufficient
      operative field. The authors describe their experience in five patients with
      basilar trunk aneurysms treated using temporary balloon occlusion and
      intraoperative digital subtraction angiography. With the patient under general
      anesthesia, a heparinized angiography catheter was guided into the dominant
      vertebral artery by means of the Seldinger technique. A silicone balloon catheter
      was introduced coaxially through the angiography catheter to the basilar artery
      just proximal to the aneurysm. The balloon was inflated tentatively to evaluate
      the appropriate inflation volume, then the balloon catheter was withdrawn back
      into the angiography catheter to prevent thrombus formation. After exposure of
      the aneurysm, the occlusion balloon was advanced again and inflated temporarily
      within the basilar artery to prevent premature rupture and to facilitate
      dissection of the aneurysm. The mean duration of temporary balloon occlusion was
      22 minutes. There were no patients with postoperative deficits attributable to
      the temporary occlusion. The results of aneurysm clip placement were confirmed by
      intraoperative digital subtraction angiography immediately after clipping. No
      patient suffered from distal embolism or other complications related to vessel
      catheterization. From this experience, it is concluded that this intraoperative
      endovascular technique can contribute to the success of surgery for complex
      cerebral aneurysms, particularly for basilar trunk aneurysms in which proximal
      vascular control is difficult.

PMID- 8283262
TI  - Extracranial-intracranial saphenous vein bypass for carotid or vertebral artery
      dissections: a report of six cases.
AB  - The management of carotid or vertebral artery dissections has generally been
      either conservative (with anticoagulation) or surgical (by proximal ligation or
      trapping procedures). However, identification and management of those patients
      with a high risk of stroke recurrence have been difficult. Six patients with
      carotid or vertebral artery dissections underwent a total of seven surgical
      procedures involving intracranial interpositional saphenous vein bypass grafts
      anastomosed distally beyond the point of dissection with trapping of the
      intermediate diseased section of the artery. It is suggested that this procedure
      be used in patients who have bilateral carotid or vertebral artery disease,
      persistent angiographic abnormalities (particularly aneurysms), or recurring
      ischemic events while undergoing anticoagulation therapy, or in whom
      anticoagulation is undesirable. This procedure has benefits over current surgical
      options because of the maintenance of high flow, the avoidance of abnormal
      watershed areas of flow, and the elimination of the risk of emboli. The procedure
      is compared to previous techniques of extracranial-intracranial bypass.

PMID- 8283263
TI  - Cognitive functioning in long-term survivors of high-grade glioma.
AB  - In a pilot study, two groups of patients with malignant glioma underwent
      sequential neuropsychological evaluations after successful tumor treatment. Group
      1 included nine patients treated from 1981 to 1985; all patients received
      irradiation and eight underwent chemotherapy. The baseline neuropsychological
      assessment was performed 1 to 63 months after tumor diagnosis, with follow-up
      evaluations at irregular intervals over the next 3 to 7 years. Six patients in
      Group 1 exhibited impairment on most measures at baseline; subsequently, two
      patients developed profound cognitive impairment. Initially, three patients
      functioned in the average range on most tasks; thereafter, two deteriorated on
      one measure each. Group 2 was ascertained prospectively and included 16 patients
      treated from 1985 to 1987, all of whom received irradiation and chemotherapy. The
      first evaluation was performed 18 months after diagnosis, then every 6 months for
      2 years, and then yearly. Compared to a control group, those in Group 2 had
      significant cognitive impairment at baseline. Cognitive performance did not
      change over the next 12 months in 10 patients who remained free of tumor, but
      within 2 years of baseline testing, deterioration on specific tasks was evident
      in two of seven disease-free survivors. When last tested, five of six disease
      free survivors had deteriorated on one or more measures. Unlike Group 1, severe
      global cognitive impairment was not seen, perhaps because Group 2 was followed
      for a shorter time. Verbal and nonverbal composite scores derived from
      intelligence quotient (IQ) tests showed less impairment at baseline than did
      other measures and were more likely to remain stable subsequently. Verbal memory
      and sustained attention were the most impaired at baseline, and verbal learning
      and flexibility in thinking showed the greatest tendency to decline over time.
      Cognitive functioning in survivors of high-grade glioma is best measured and
      monitored by tests that probe a broader spectrum of abilities than IQ.
      Neuropsychological measures used in this analysis lacked sensitivity at the lower
      end of the impaired range. Future studies should use tests better able to discern
      cognitive differences at low performance levels. Based on this experience, the
      authors conclude that most long-term survivors of high-grade glioma will have
      significant cognitive difficulties, usually evident by the first assessment; some
      patients will develop profound impairment years later, and few are capable of
      fully independent living.

PMID- 8283264
TI  - Labeled Schwann cell transplants versus sural nerve grafts in nerve repair.
AB  - This study evaluated the ability of Schwann cell transplants to enhance the
      recovery of function in injured nerves and compared the results to those produced
      by sural nerve grafts. Schwann cells were isolated from sciatic nerves,
      prelabeled with gold fluorescent dye admixed with collagen gel, and placed in
      resorbable collagen tubes. Twenty-four adult rats underwent severing of the
      bilateral sciatic nerves, with a 10-mm gap between the nerve stumps. The rats
      were then divided into two groups. A collagen tube with implanted Schwann cells
      was implanted in one leg of the Group I rats, and the contralateral leg served as
      a control and was repaired with a collagen tube filled with collagen gel only.
      The Group II animals received conduits packed with labeled Schwann cells in one
      leg to bridge the 10-mm gap; the contralateral leg was repaired with an
      autogenous sural nerve graft. Recovery of function was assessed physiologically
      and morphologically. Nerve conduction velocity and nerve action potential
      amplitude measurements showed that the Schwann cell implants induced return of
      function comparable to that of the sural nerve grafts. Morphological assessments
      of myelination suggested a tendency toward greater numbers of myelinated axons in
      Schwann cell implants than in sural nerve grafts. Anatomical analyses of gold
      fluorescent dye showed both high viability of prelabeled Schwann cells at 120
      days after transplantation and migration as far as 30 mm away from the implant
      site.

PMID- 8283265
TI  - Intracellular mechanisms involved in the responses of cerebrovascular smooth
      muscle cells to hemoglobin.
AB  - An investigation was undertaken of the mechanism by which oxyhemoglobin and its
      analog methemoglobin might cause cerebrovascular spasm. The effect of these
      compounds on the levels of intracellular inositol triphosphate and calcium in
      cultured primate cerebrovascular smooth-muscle cells and the contractile action
      of oxyhemoglobin on isolated rings of primate cerebral arteries were also
      examined. Oxyhemoglobin, but not methemoglobin, produces a transient but highly
      significant increase in the intracellular levels of inositol triphosphate.
      Intracellular calcium levels in these cells are increased by thrombin, aluminum
      tetrafluoride, and oxyhemoglobin, and the sustained elevation in intracellular
      calcium is prevented by ethyleneglycol tetra-acetic acid and the phospholipase C
      inhibitor neomycin. Removal of the oxyhemoglobin after as long as 48 hours'
      incubation with this compound allowed cells to rapidly reduce their intracellular
      calcium levels to near normal. Oxyhemoglobin produced contractions of isolated
      rings of both normal and spastic cerebral arteries, although the response of
      spastic vessels was significantly smaller. This effect was inhibited by neomycin.
      The addition of neomycin relaxed arteries that were contracted with
      oxyhemoglobin, 5-hydroxytryptamine, or potassium chloride. It is thus likely that
      activation of phospholipase C is a critical step in the development of vasospasm,
      but the transient nature of the response to inositol triphosphate suggests that
      the sustained contraction may arise from other phospholipase C-dependent
      mechanisms.

PMID- 8283266
TI  - Changes in Ca(++)-ATPase activity in smooth-muscle cell membranes of the canine
      basilar artery with experimental subarachnoid hemorrhage.
AB  - Changes in Ca(++)-adenosine triphosphatase (ATPase) activity in the plasma
      membrane of smooth-muscle cells in the basilar arteries of dogs with experimental
      subarachnoid hemorrhage (SAH) were examined. The study methods included electron
      microscopic histochemistry and bioassay of the enzyme that exports cytoplasmic
      Ca++ to extracellular spaces. The Ca(++)-ATPase activity in the basilar artery
      increased significantly in response to the application of vasoconstrictive agents
      (prostaglandin F2 alpha and a phorbol ester), but decreased significantly 24
      hours after experimental SAH, inversely with basilar artery contraction. Dogs
      that had undergone two arterial blood injections (double SAH) exhibited a further
      decrease in Ca(++)-ATPase activity as well as persistent contraction of the
      basilar artery for a longer period (at least 7 days) than was seen in animals
      with a single arterial blood injection. Bioassay of the enzyme also demonstrated
      a decrease in vascular Ca(++)-ATPase activity in dogs subjected to double SAH.
      These findings suggest that the early occurrence of and long-lasting decrease in
      Ca(++)-ATPase activity in dogs with experimental SAH induces a persistent
      disturbance of Ca++ homeostasis and indicates that damage to the plasma membrane
      in the cerebral arterial smooth-muscle cells proceeds to myonecrosis after SAH.

PMID- 8283267
TI  - The role of active smooth-muscle contraction in the occurrence of chronic
      vasospasm in the canine two-hemorrhage model.
AB  - To evaluate the pathogenetic role of alterations in the physical properties of
      the arterial wall (the passive component) and of active smooth-muscle contraction
      (the active component) in the occurrence of chronic vasospasm, the temporal
      profiles of these events were examined using the canine "two-hemorrhage" model.
      In the in vivo study, the basilar artery was exposed via the transclival approach
      on Day 0, 2, 4, 7, or 14. Nicardipine, followed by the protein kinase C inhibitor
      H-7, then papaverine were administered in a cumulative fashion, and the change in
      the basilar artery diameter induced by the addition of each agent was recorded
      angiographically. Drug administration markedly reversed the arterial narrowing
      caused by chronic vasospasm. When the vasodilatory effect of each agent was
      compared, the dilation induced by nicardipine or papaverine progressively
      decreased from Day 2 to Day 7, whereas that induced by H-7 increased. The in
      vitro experiment using arterial segments excised from the basilar artery revealed
      a progressive increase in arterial stiffness from Day 2 to Day 7. Also, there was
      a significant decrease in the initial half-circumference of the arterial segment,
      which was at its maximum on Days 4 and 7. However, the alteration in the initial
      half-circumference was considerably less than that in the angiographic diameter
      following subarachnoid hemorrhage. These data indicate that the augmented
      spontaneous tonus of the smooth muscle plays the predominant role in the
      occurrence of chronic vasospasm. Thus, the involvement of the protein kinase C
      mediated contractile system is strongly suggested.

PMID- 8283268
TI  - Biodegradable polymers for controlled delivery of chemotherapy with and without
      radiation therapy in the monkey brain.
AB  - Sustained drug delivery by biodegradable polymer devices can increase the
      therapeutic efficacy of drugs by producing high local tissue concentrations over
      extended periods of time. It has been shown previously that implantation of
      controlled-release polymers impregnated with the nitrosourea carmustine (BCNU)
      extended the period of survival in rats bearing the 9L glioma compared with
      similar rats treated with systemically administered BCNU. This study evaluated
      the effect on the monkey brain of interstitial delivery of BCNU by the
      biodegradable polyanhydride copolymer poly[bis(p-carboxyphenoxy)propane]anhydride
      (PCPP) and sebacic acid (SA) in a 20:80 formulation (PCPP:SA). The effect of
      combining interstitial BCNU with radiation therapy was also evaluated. Eighteen
      male cynomolgus monkeys were randomly assigned to one of four groups: a control
      group; a group with implantation of empty polymer; a group with implantation of
      BCNU-loaded polymer; and a group with implantation of empty polymer in the right
      hemisphere and BCNU-loaded polymer in the left hemisphere, followed by
      irradiation. The effects were evaluated radiologically and histologically at
      specified times. A local reaction by the brain to the polymer was found, which
      was greater when the polymer contained BCNU. Local cerebral edema was observed
      radiographically on postoperative Day 14 and had resolved by Day 72.
      Histologically, a subacute cellular inflammatory response was seen on
      postoperative Day 16, which had changed to a chronic inflammatory response by Day
      72. In the group with radiation therapy administered to the hemisphere bearing
      BCNU-loaded polymer, only localized pathological changes were detected. In all
      animals, brain distant from the polymer implantation site was normal. No
      neurological or general deleterious effects were seen in any of the animals. It
      is concluded that the interstitial delivery of BCNU by the polyanhydride polymer
      PCPP:SA is safe in the primate brain and that concomitant radiation therapy did
      not lead to any adverse effects. These experimental findings are important to an
      understanding of the clinical effects of PCPP:SA implants in treating brain
      diseases.

PMID- 8283269
TI  - A new model of diffuse brain injury in rats. Part I: Pathophysiology and
      biomechanics.
AB  - This report describes the development of an experimental head injury model
      capable of producing diffuse brain injury in the rodent. A total of 161
      anesthetized adult rats were injured utilizing a simple weight-drop device
      consisting of a segmented brass weight free-falling through a Plexiglas guide
      tube. Skull fracture was prevented by cementing a small stainless-steel disc on
      the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to
      establish fracture threshold; and Group 2, consisting of 107 animals, to
      determine the primary cause of death at severe injury levels. Data from Group 1
      animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted
      in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact
      was followed by apnea, convulsions, and moderate hypertension. The surviving rats
      developed decortication flexion deformity of the forelimbs, with behavioral
      depression and loss of muscle tone. Data from Group 2 animals suggested that the
      cause of death was due to central respiratory depression; the mortality rate
      decreased markedly in animals mechanically ventilated during the impact. Analysis
      of mathematical models showed that this mass-height combination resulted in a
      brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is
      concluded that this simple model is capable of producing a graded brain injury in
      the rodent without a massive hypertensive surge or excessive brain-stem damage.

PMID- 8283270
TI  - A new model of diffuse brain injury in rats. Part II: Morphological
      characterization.
AB  - A new model producing diffuse brain injury, without focal brain lesions, has been
      developed in rats. This has been achieved by allowing a weight of 450 gm to fall
      onto a metallic disc fixed to the intact skull of the animal which is supported
      by a foam bed. Two levels of injury were examined by adjusting the height of the
      falling weight to either 1 m or 2 m. Two groups of animals were studied. Group 1
      animals were separated into three subgroups: 10 received a 1-m weight drop, 58
      received a 2-m weight drop, and 13 served as controls; all were allowed to
      breathe spontaneously. Group 2 animals were separated into the same subgroups:
      four received a 1-m weight drop, six received a 2-m weight drop, and four served
      as controls; all of these were mechanically ventilated during the procedure. In
      Group 1, morphological studies using light and electron microscopy were performed
      at 1, 6, 24, or 72 hours, or 10 days after insult; all Group 2 rats were studied
      at 24 hours after injury. Results from Group 1 animals showed that no mortality
      occurred with the 1-m level injury, while 59% mortality was seen with the 2-m
      level injury. On the other hand, no mortality occurred in Group 2 animals
      regardless of the level of trauma induced. However, the morphological changes
      observed in both groups were similar. Gross pathological examination did not
      reveal any supratentorial focal brain lesion regardless of the severity of the
      trauma. Petechial hemorrhages were noticed in the brain stem at the 2-m level
      injury. Microscopically, the model produced a graded widespread injury of the
      neurons, axons, and microvasculature. Neuronal injury was mainly observed
      bilaterally in the cerebral cortex. Brain edema, in the form of pericapillary
      astrocytic swelling, was also noted in these areas of the cerebral cortex and in
      the brain stem. Most importantly, the trauma resulted in a massive diffuse axonal
      injury that primarily involved the corpus callosum, internal capsule, optic
      tracts, cerebral and cerebellar peduncles, and the long tracts in the brain stem.
      It is concluded that this model would be suitable for studying neuronal, axonal,
      and vascular changes associated with diffuse brain injury.

PMID- 8283271
TI  - Isolated cerebellar lymphomatoid granulomatosis progressing to malignant
      lymphoma. Case report.
AB  - A 60-year-old man presented with progressive and unique neurological symptoms.
      Investigations identified an isolated cerebellar lesion. This lesion fulfilled
      the histological criteria for lymphomatoid granulomatosis, and in situ
      hybridization and deoxyribonucleic acid (DNA) dot blot techniques revealed
      significant amounts of Epstein-Barr virus DNA within the tumor cells. The patient
      underwent cranial radiation therapy, and 16 months after the initial presentation
      the lesion evolved into a malignant lymphoma. He subsequently died secondary to
      subdural empyema, bacterial meningitis, and bronchopneumonia. The unique clinical
      and etiological aspects of this case are addressed.

PMID- 8283272
TI  - Hydrocephalus due to villous hypertrophy of the choroid plexus in the lateral
      ventricles. Case report.
AB  - A case is reported of hydrocephalus due to overproduction of cerebrospinal fluid
      (CSF) caused by villous hypertrophy of the choroid plexus in the lateral
      ventricles. A 7-year-old girl with mental retardation developed gait disturbance;
      hydrocephalus and a Dandy-Walker cyst were detected on computerized tomography.
      She was initially treated with a ventriculoperitoneal shunt; however, shunting
      failed to control the hydrocephalus. The excessive outflow of CSF suggested
      choroid plexus abnormality, and magnetic resonance (MR) imaging revealed
      enlargement of the choroid plexus in both lateral ventricles. The patient was
      therefore diagnosed as having hydrocephalus induced by overproduction of CSF,
      which was controlled by resection of the choroid plexus. Histological examination
      showed the structure typical of normal choroid plexus. This is a rare case of
      villous hypertrophy of the choroid plexus in which MR imaging assisted in the
      diagnosis.

PMID- 8283273
TI  - Documented reversal of global ischemia immediately after removal of an acute
      subdural hematoma. Report of two cases.
AB  - The authors report two cases of severe head injury with acute subdural hematoma,
      in which cerebral blood flow (CBF) and cerebral blood volume (CBV) measurements
      were obtained prior to evacuation of the subdural hematoma and again immediately
      after removal. The first patient, a 21-year-old man with a motor response
      localizing to pain, had a global CBF of 18.2 ml/100 gm/min and a decreased global
      CBV of 3.7 ml/100 gm at 2.3 hours after injury. Immediately after removal of the
      subdural hematoma (8.1 hours after injury), CBF and CBV measurements revealed
      increases to 35.5 ml/100 gm/min and 5.8 ml/100 gm, respectively. The second
      patient, a 49-year-old woman with a normal flexor motor response to pain, had
      preoperative global values of 15.8 ml/100 gm/min for CBF and 2.0 ml/100 gm for
      CBV at 3 hours after injury. Postoperatively (9.3 hours after injury), the CBF
      and CBV values increased to 41.6 ml/100 gm/min and 4.0 ml/100 gm, respectively.
      The first patient, with only borderline ischemia and removal of the subdural
      hematoma within 3 hours, made a good recovery, while the second patient, with
      prolonged lower levels of CBF, remained in a persistent vegetative state. The low
      values of preoperative CBV argue for compression of the microcirculation as the
      cause of ischemia.

PMID- 8283274
TI  - Moyamoya disease with repeated intraventricular hemorrhage due to aneurysm
      rupture. Report of two cases.
AB  - Two cases of moyamoya disease associated with repeated intraventricular
      hemorrhage are reported. The origin of bleeding was thought to be a distal
      aneurysm of the choroidal artery. The aneurysms were confirmed radiologically and
      histologically. The relationship between moyamoya disease and aneurysms is
      discussed, and a treatment proposed.

PMID- 8283275
TI  - Transcranial Doppler ultrasound findings in cerebral venous sinus thrombosis.
      Case report.
AB  - Transcranial Doppler ultrasound (TCD) findings are described in a patient with
      acute thrombosis of the sagittal venous sinus. The TCD finding of prominent
      venous signals adjacent to the middle cerebral artery gave the first indication
      of the diagnosis, which was subsequently confirmed by computerized tomography.
      Awareness of the possible TCD findings in patients with a similar history may
      lead to a more rapid diagnosis of cerebral venous sinus thrombosis.

PMID- 8283276
TI  - Wrap-clipping with a Dacron mesh silastic sheet. Technical note.
AB  - A technique combining wrapping and clipping using a Silastic sheet coated with
      Dacron mesh is described for treatment of fusiform or broad-based cerebral
      aneurysms. This sheet is easily tailored to wrapping the aneurysm base while
      avoiding involvement of the cranial nerves or branching vessels. The sheet is
      semitransparent so that the caliber of the newly constructed parent artery is
      easily adjusted during wrap-clipping. After the aneurysm and the parent artery
      have been circumferentially wrapped with the sheet, aneurysm clips are applied on
      the sheet so that the base of the aneurysm is clipped between the two leaves of
      the sheet. This wrap-clipping technique avoids the risks involved in extracting
      the aneurysm from the parent artery. The Dacron mesh coating the outer surface
      and sufficient clip closing pressure are both helpful in preventing the clip
      blades from sliding. Similar previously reported techniques are reviewed and
      discussed in detail.

PMID- 8283277
TI  - "Trap door" exposure of the cervicothoracic junction. Technical note.
AB  - This report describes a "trap door" exposure of the cervicothoracic junction. The
      method combines a standard anterior approach to the spine along the medial border
      of the sternocleidomastoid muscle with both a partial median sternotomy and an
      anterolateral thoracotomy. Transection of the clavicle is not required and the
      sternoclavicular joint is preserved. With this method, all important ventral
      paravertebral vessels, nerves, and associated soft tissue are fully identified
      and readily mobilized as needed. The method provides full bilateral anterior
      exposure from the C-4 through at least the T-3 vertebral levels, as well as
      unilateral anterolateral access to the upper thoracic spine.

PMID- 8283278
TI  - Louise Eisenhardt, M.D.: first editor of the Journal of Neurosurgery (1944-1965).
AB  - This is a literary portrait of Louise Eisenhardt, M.D., associate of Harvey
      Cushing, scholar, investigator, editor, teacher, and curator of the Brain Tumor
      Registry at Yale. She was a Charter Member of the Harvey Cushing Society which
      she served as President, long-term Secretary-Treasurer, and Historian. She
      achieved many "firsts" for women in medicine. A figure in the Homeric tradition
      of observing accurately and reporting honestly, Dr. Eisenhardt set high standards
      for both colleagues and students as well as for aspiring medical authors. She
      left a tradition worthy of emulation.

PMID- 8283279
TI  - Survival in malignant gliomas.

PMID- 8283280
TI  - Treatment of brain metastasis.

PMID- 8283281
TI  - Foundation for international education in neurosurgery.

PMID- 8283282
TI  - Preservation of olfaction.

PMID- 8283283
TI  - Repair of facial nerve.

PMID- 8283284
TI  - Hypoglossal-facial nerve anastomosis.

PMID- 8283285
TI  - Spinal angiolipomas.

PMID- 8283286
TI  - Dietary cysteic acid serves as a precursor of taurine for cats.
AB  - The ability of cats to use dietary cysteic acid as a precursor for taurine was
      examined. For 39 wk, six groups of four specific-pathogen-free cats each were fed
      purified diets that provided either 1.25 g taurine or 0, 1.0, 2.0, 10 or 20 g
      cysteic acid/kg diet. Concentrations of taurine in plasma and whole blood were
      measured weekly for 13 wk and monthly until 39 wk. Muscle concentrations of
      taurine at 12 wk were measured on a biopsy sample of the semitendinosus muscle.
      Fecal and urinary excretions of taurine and cysteic acid at 17 wk were measured.
      Concentrations of taurine in plasma and whole blood were linearly and positively
      correlated with cysteic acid in the diet (r2 = 0.88). Urinary taurine, a major
      route of excess taurine excretion, was positively correlated with the cysteic
      acid concentration of the diet (r2 = 0.94). Muscle and whole-blood taurine
      concentrations were also positively correlated (r2 = 0.96) with dietary cysteic
      acid concentration. Gross and histopathological examinations were performed on
      cats fed diets containing 20 g cysteic acid/kg diet. No adverse gross clinical
      signs were observed in cats fed any diets containing cysteic acid; minor
      histopathologic changes of the pancreas and thyroid were found in three of four
      cats fed 20 g cysteic acid/kg diet. Results suggest that cats are able to use
      dietary cysteic acid as a precursor for taurine biosynthesis.

PMID- 8283287
TI  - Unsaturated fat and low energy intake induce whereas an increment in energy
      intake ameliorates fatty liver during prolonged alcohol consumption by rats.
AB  - Two groups of rats were fed liquid diets containing 35% of energy as fat and
      either 36 or 26% of energy as alcohol to examine the effect of fat and energy
      intake on alcoholic fatty liver production. After 4 wk, five rats in each group
      were killed for analysis of liver triglyceride concentration, and then the
      alcohol diets fed to remaining rats were switched. All remaining rats were killed
      for hepatic triglyceride determination after another 4 wk. Rats initially fed the
      36% alcohol diet or those switched to this diet ingested less energy, exhibited
      alcoholemia and slow growth, and developed fatty livers. Rats initially fed the
      26% alcohol diet or those switched to this diet ingested significantly more
      energy, high amounts of alcohol and fat, exhibited low alcoholemia and faster
      growth than when they were fed the 36% alcohol diet. Fatty liver was absent in
      rats fed the 26% alcohol diet but was induced when they were fed the 36% alcohol
      diet. Fatty liver in rats initially fed the 36% alcohol diet regressed completely
      when the rats were switched to the 26% alcohol diet. Additional studies employing
      36% alcohol diets containing 35% of energy as fat, derived from either corn oil
      or olive oil, revealed that unsaturated fat and not specifically linoleate plays
      a role in the induction of fatty liver. Thus, nutritional factors regulate the
      induction or regression of fatty liver and alcoholemia in alcoholic rats.

PMID- 8283288
TI  - Relationship between glucose tolerance factor and low-molecular-weight chromium
      binding substance.

PMID- 8283289
TI  - Expression of cysteine-rich intestinal protein in rat intestine and transfected
      cells is not zinc dependent.
AB  - The cysteine-rich intestinal protein (CRIP) is a member of a superfamily of
      proteins containing the LIM motif (a double zinc finger) that has been shown to
      bind zinc. The role of zinc in the regulation of CRIP was examined in adult rats,
      cultured intestinal epithelial cells and in a transient transfection system. When
      adult male rats were fed diets with various amounts of zinc, the amount of ileal
      CRIP mRNA was only 19% lower in rats fed a zinc-deficient diet (1 mg Zn/kg) and
      was not different in the zinc-supplemented group (180 mg Zn/kg) compared with the
      zinc-adequate group (30 mg Zn/kg). In contrast, metallothionein mRNA levels were
      76% lower and 80% greater than control levels in the zinc-deficient and zinc
      supplemented groups, respectively. Using the chloramphenicol acetyltransferase
      (CAT) reporter gene, 5'-deletion products of the CRIP genomic promoter were
      tested for basal and zinc-induced CAT activity in transiently transfected IEC-6
      cells. Treatment of the cells with zinc did not alter CAT activity of any
      construct. These results suggest that CRIP is not directly regulated by zinc in
      the intestine of rats.

PMID- 8283290
TI  - Lactobacillus strain GG supplementation decreases colonic hydrolytic and
      reductive enzyme activities in healthy female adults.
AB  - The effects of yogurt containing viable Lactobacillus strain GG (L. GG) and/or
      fiber supplements on fecal enzyme activities (beta-glucuronidase, nitroreductase,
      beta-glucosidase, glycocholic acid hydrolase, urease) and on bacterial
      metabolites in urine (phenol, p-cresol) were studied in 64 females, 20-41 y old.
      The subjects were randomly divided into three groups: the first group received L.
      GG yogurt (2 x 150 mL/d, containing 10(11) colony-forming units (cfu)/L of L.
      GG), the second group received L. GG yogurt and a rye fiber product (30 g/d,
      equivalent to 9 g fiber/d), and the third group received placebo yogurt
      (pasteurized) and fiber. The supplementation period lasted 4 wk, with a preceding
      2-wk baseline period and a 2-wk follow-up period. The mean fecal count of L. GG
      was approximately 10(6) cfu/g feces during the supplementation, and L. GG
      persisted in the fecal samples of 28% of the subjects for 2 wk after
      supplementation. L. GG yogurt alone or with fiber significantly decreased fecal
      beta-glucuronidase, nitroreductase and glycocholic acid hydrolase activities.
      These enzyme activities returned to baseline levels during the follow-up period.
      beta-Glucosidase and urease activities were not altered significantly during the
      study. The addition of fiber to L. GG and placebo yogurt had no effect on the
      enzymic activities. Urinary excretion of p-cresol decreased significantly in
      groups receiving L. GG. These data demonstrate that L. GG can modify the colonic
      environment with possible health effects.

PMID- 8283291
TI  - Changes in maternal upper arm fat stores are predictors of variation in infant
      birth weight.
AB  - The relationship between changes in maternal subcutaneous fat and infant birth
      weight was studied in 608 low income women. A loss of upper arm fat area (> 6.4
      cm2), measured from 28 wk gestation to 4-6 wk postpartum, was associated with
      greater birth weight (+144 g, P < 0.01). However, when pregravid weight was low
      (< 25th percentile for age), a loss of upper arm fat area was associated with a
      birth weight lower by more than 300 g than that for women with higher pregravid
      weights who also lost fat, indicating that maternal stores among those with low
      weight may have been relatively depleted. Continued gains in upper arm fat area
      (> 5 cm2) from 28 wk gestation to the postpartum period was also associated with
      a lower birth weight (-123 g, P < 0.02). The mothers who gained upper arm fat
      late in pregnancy or continued to accrue fat in the postpartum period had the
      largest gestational weight gains, bore infants who were smaller, and retained the
      most weight postpartum. Thus, change in upper arm fat is a significant predictor
      of variation in infant birth weight.

PMID- 8283292
TI  - Prune fiber or pectin compared with cellulose lowers plasma and liver lipids in
      rats with diet-induced hyperlipidemia.
AB  - Previous research indicated that prunes in the diet of men with
      hypercholesterolemia lowered plasma and LDL cholesterol concentrations. To
      further study lipid metabolism in response to ingesting prunes, we conducted an
      animal study to test the hypotheses that fiber extracted from prunes, compared
      with purified cellulose, lowers plasma and liver cholesterol in rats with diet
      induced hyperlipidemia and that the response is dose dependent. Rats were
      randomly assigned to one of five experimental diet groups. Four of the diets
      contained cholesterol and cholic acid to induce hyperlipidemia. The fiber source
      in the hyperlipidemic diets was 6% cellulose, 3% prune fiber, 6% prune fiber or
      3% pectin. The fifth group, the nonhyperlipidemic control, was fed a diet
      containing 6% cellulose without cholesterol or cholic acid. Rats consumed one of
      the five diets ad libitum for 28 d, then were killed after 16 h without food.
      Plasma, LDL and liver cholesterol concentrations were higher in the
      hyperlipidemic control than the nonhyperlipidemic control and lower in the groups
      fed diets containing pectin or prune fiber than in the hyperlipidemic control
      group. No differences in plasma or liver cholesterol concentrations were detected
      between groups fed either dose level of prune fiber or between groups fed 6%
      prune fiber and pectin. These results indicate that fiber extracted from prunes
      lowers plasma and liver cholesterol in hyperlipidemic rats, although a dose
      dependent response was not detected.

PMID- 8283293
TI  - Leucine oxidation changes rapidly after dietary protein intake is altered in
      adult women but lysine flux is unchanged as is lysine incorporation into VLDL
      apolipoprotein B-100.
AB  - We measured the 13C enrichments of expired CO2 and deuterium enrichments of
      plasma free lysine and VLDL-apolipoprotein B-100 in five nulliparous women who
      received an oral bolus dose of [1-13C]leucine and a primed, constant infusion of
      [2H4]lysine on d 2 and 6 while consuming protein diets of 1.5, 1.0 and 0.4 g.kg-1
      x d-1. Peak enrichments and cumulative percent recoveries of 13C in expired CO2
      increased during the high, and decreased during the low protein periods within 24
      h of altered intakes; these changes averaged 89% of that on d 6 of the high and
      low protein diets. The early changes in leucine oxidation showed significant
      relationships with urinary nitrogen excretion on d 6 of the dietary periods. The
      ratio of the isotopic enrichment of lysine in VLDL-apolipoprotein B-100 to that
      in plasma was unaltered by the level of protein intake. Thus, amino acid
      oxidation adapts rapidly to altered protein intakes in adult women and is useful
      to determine protein needs during rapidly changing physiologic conditions.
      However, 6-d periods of protein intake over the range of 1.5 to 0.4 g.kg-1 x d-1
      do not affect the proportional use of dietary amino acids for hepatic secretory
      protein synthesis.

PMID- 8283294
TI  - Galactosylsucrose and xylosylfructoside alter digestive tract size and
      concentrations of cecal organic acids in rats fed diets containing cholesterol
      and cholic acid.
AB  - Influences of galactosylsucrose and xylosylfructoside on body mass gain, the
      digestive tract mass and concentrations of organic acids such as acetic,
      propionic, butyric, lactic and succinic acid in the cecum were compared among
      rats fed a cholesterol-enriched fiber-free diet [cholesterol 6 + cholic acid 1.5
      (g/kg)] containing either galactosylsucrose, xylosylfructoside or sucrose (100
      g/kg) or the above fiber-free diet without test sugar (control) for 21 d. Body
      mass gain was greater in rats fed sucrose, but not in rats fed galactosylsucrose
      or xylosylfructoside, than in control rats. The mass of the small intestine and
      colon plus rectum was larger in rats fed xylosylfructoside than in control rats.
      Cecal contents and cecal tissue mass were heavier, water content of cecal
      contents was higher, and pH and ammonia concentration of cecal contents were
      lower in rats fed diets containing xylosylfructoside than in control rats.
      Galactosylsucrose had similar effects, although not all differences were
      significant. The concentration of hydrogen ion in cecal contents positively
      correlated to total cecal concentration of measured organic acids and to amount
      of cecal contents. Total concentration of measured organic acids in cecal
      contents positively correlated to cecal tissue mass. The estimated contribution
      of galactosylsucrose, xylosylfructoside and sucrose for body mass deposition were
      0.19, -0.29 and 0.51 (g body mass gained/g sugar), respectively.

PMID- 8283295
TI  - Rapid postabsorptive metabolism of nicotinic acid in rat small intestine may
      affect transport by metabolic trapping.
AB  - Postabsorptive metabolism of [3H]nicotinic acid by rat proximal jejunum was
      studied in vitro using the everted sac technique and in vivo by applying ligated
      loops. Metabolites were analyzed by HPLC with radiochemical detection. Within 60
      min of incubation nicotinic acid was almost completely metabolized in vivo. Only
      3.2% of the label could be detected in the original substrate nicotinic acid,
      whereas > 90% of the radioactivity present in the gut wall was nicotinamide.
      Further in vitro experiments revealed that conversion was rapid; after 10 min of
      incubation > 40% of the substrate was converted to other metabolites. From
      analysis of the serosal fluid, it was evident that only nicotinic acid and
      nicotinamide were transferred to the serosal compartment. Rapid conversion of
      nicotinic acid might affect the transport step itself by metabolic trapping,
      resulting in the maintenance of a substrate gradient necessary for passive
      absorption. In contrast, as examined by gradient centrifugation, the substrate in
      subcellular organelles is transferred only to a minor extent.

PMID- 8283297
TI  - Ten different dietary fibers have significantly different effects on serum and
      liver lipids of cholesterol-fed rats.
AB  - The comparative effects of 10 different dietary fibers on serum and liver lipids
      were investigated by feeding male Sprague-Dawley rats diets containing 10 g
      cholesterol + 2 g cholic acid/kg diet, with 60 g fiber/kg diet. Diets were fed
      for 3 wk; cellulose was the control fiber. Rats fed psyllium (rich in soluble
      fiber) had the lowest serum and liver cholesterol concentrations. Rats fed other
      soluble fiber-rich fibers (oat gum, guar gum and pectin) also had significantly
      lower serum and liver cholesterol concentrations than rats fed cellulose.
      Although feeding diets containing both soluble and insoluble fibers (soybean
      fiber and oat bran) did not significantly alter serum cholesterol, liver
      cholesterol values were significantly lower than those of cellulose-fed rats.
      Rats fed rice bran, predominantly an insoluble fiber source, had significantly
      higher liver cholesterol and significantly lower body weight gains and serum
      triglyceride concentrations than cellulose-fed rats. Values for serum and liver
      cholesterol were similar for rats were fed insoluble-rich fibers (corn bran,
      cellulose and wheat bran). These observations indicate that feeding dietary
      fibers rich in soluble fiber produces lower serum and liver cholesterol
      concentrations than does feeding commonly available sources of water-insoluble
      fiber.

PMID- 8283296
TI  - Abomasal casein infusion enhances the mitogenic activity of serum from protein
      restricted steers.
AB  - Holstein steers fed protein-restricted diets were used to evaluate protein
      realimentation and site of serum collection on the ability of calf serum to
      affect proliferation, protein synthesis and degradation in L6 myoblast cell
      culture bioassay. In Experiment 1, five steers (average weight 227 kg) received
      continuous abomasal infusion of 4 L of water or casein (50% of basal dietary
      nitrogen intake) in a switchback design. Serum was collected 2 d before and after
      1, 3, 5, 7 and 9 d of infusion. Abomasal casein infusion increased serum
      mitogenic activity, nitrogen retention (119%) and total post-ruminal amino acid
      flow (78%). In Experiment 2, serum was collected from the jugular and femoral
      veins and the carotid artery before and after 7 d of abomasal casein infusion.
      Serum from calves abomasally infused with casein increased myoblast proliferation
      (jugular > femoral > carotid) and protein synthesis and decreased protein
      degradation in cultured myotubes. The addition of test calf serum inhibited the
      mitogenic activity of control calf serum. Results suggest that post-ruminal amino
      acid flow and site of serum collection alter the ability of serum to influence
      cell culture bioassays.

PMID- 8283298
TI  - Emulsification and fatty acid chain length affect the kinetics of [14C]-medium
      chain triacylglycerol utilization by neonatal piglets.
AB  - In vivo oxidation kinetics of medium-chain triglycerides (MCT) composed of [1
      14C]hexanoate (tri-6:0) or [1-14C]octanoate (tri-8:0) were compared after being
      fed to day-old piglets (1.4 kg; n = 4/treatment). Animals were fitted with
      arterial and oro-gastric catheters and placed into respiration chambers held at
      35 degrees C. The radiolabeled MCT were fed in equimolar amounts (6.5
      mmol/kg0.75), in either nonemulsified form or as 30% (v/v) emulsions, using
      polyoxyethylene sorbitan monooleate as an emulsifier. Expired CO2 was quantified
      and specific radioactivity (Bq/mumol) determined at 20-min intervals over 24 h,
      and serial blood samples were drawn for measurement of plasma hexanoate and
      octanoate by HPLC. The rate [mumol/(h.kg0.75)] and extent (mmol/kg0.75) of MCT
      oxidative utilization (i.e., composite of digestion, absorption and oxidation)
      were calculated from the kinetics of 14CO2 expiration. Emulsification increased
      both the rate and extent of MCT oxidative utilization by > 20% regardless of
      fatty acid chain length (P < 0.05). Maximal MCT oxidation rates occurred at 3.5 h
      after feeding and were sufficient to meet up to 48% of the piglets' energy
      expenditure. The maximal rate of tri-6:0 oxidative utilization exceeded that of
      tri-8:0 by 37% (P < 0.05), but the extent of utilization was not affected by
      fatty acid chain length. Plasma medium-chain fatty acid concentrations were in
      agreement with these observations, being higher in pigs fed emulsified MCT than
      in pigs fed nonemulsified MCT (P < 0.05) and being higher in pigs fed tri-6:0
      than in animals fed tri-8:0 (P < 0.05). Collectively, these data demonstrate that
      newborn piglets can effectively digest, absorb and oxidize MCT, that utilization
      is improved with emulsification, and that tri-6:0 is utilized more rapidly than
      tri-8:0.

PMID- 8283299
TI  - Glucose-restricted diets alter milk composition and mammary gland development in
      lactating rat dams.
AB  - To examine the effects of chronic restriction of maternal dietary glucose on
      lactational performance, pregnant dams were fed one of four isoenergetic diets
      containing graded levels of glucose (0, 12, 24 and 60%) from d 2 of pregnancy to
      d 15 of lactation. Dams fed the 0% glucose diet produced colostrum with higher
      protein and lower lactose and fat concentrations than normal, but all pups born
      to these dams failed to survive more than 24 h postpartum. Dams fed glucose
      restricted diets (12 and 24%) had significantly lower d 15 milk fat concentration
      than dams fed the control diet, but there were no differences in milk protein,
      lactose and glucose concentrations. On d 15, pups suckling dams fed the 12%
      glucose diet had significantly lower body weights than pups of dams fed 24 and
      60% glucose diets. Restriction of dietary glucose to 12% resulted in
      significantly smaller mammary gland cell size but failed to produce any
      significant differences in mammary gland composition (protein, fat and glycogen).
      The results indicate that the level of glucose in the maternal diet is an
      important determinant of milk composition and that > 24% glucose is needed for
      optimal milk fat concentration, whereas 12% dietary glucose is sufficient to
      sustain normal milk lactose concentration. The altered lactational performance in
      response to dietary glucose restriction was not mediated through changes in
      mammary gland composition, but in part by the reduced mammary gland size.

PMID- 8283300
TI  - Nucleotides and nutrition: role as dietary supplement.

PMID- 8283301
TI  - The biochemistry and physiology of nucleotides.
AB  - Nucleotides are phosphate esters of nucleosides that contain a sugar linked
      through a glycosidic linkage with purine and pyrimidine bases. Purine and
      pyrimidine nucleotides are major components of the cells that make up the
      monomeric units of DNA and RNA, and they function in all cellular processes.
      Biosynthesis, interconversion, catabolism and other aspects of nucleotide
      metabolism, along with various cellular roles of nucleotides, will be discussed,
      and the possible use of dietary sources of preformed purines and pyrimidines will
      be considered.

PMID- 8283302
TI  - Dietary sources of nucleotides--from breast milk to weaning.
AB  - Human breast milk contains large quantities of nucleotides compared with those in
      cow's milk and infant formulas. Dietary nucleotides may have significant effects
      in infants.

PMID- 8283303
TI  - Nucleotide uptake and metabolism by intestinal epithelial cells.
AB  - The epithelial cells of the gastrointestinal tract are the first to encounter
      ingested nucleotides. Enterocytes metabolize or transport nucleotides (often
      partially metabolized) to other cell types. Nucleotides may also affect
      enterocyte gene expression. These interactions in intestinal cell lines (Caco-2
      and IEC-6 cells) are described. Nucleotides and nucleosides are efficiently taken
      up by neoplastic cells (Caco-2) and substantially metabolized during absorption
      by epithelial monolayers. In nonmalignant cells (IEC-6), nucleotide pools are
      smaller than enterocytes of neoplastic origin (Caco-2). Consequently, cell
      proliferation in IEC-6 cells is more dependent on an external supply of
      nucleotides. Cell differentiation was examined by measuring brush border enzyme
      activities (sucrase, lactase and alkaline phosphatase). Nucleotides enhanced the
      expression of brush border enzymes in carcinoma cells only when stressed by
      glutamine deprivation. IEC-6 cells, which are poorly differentiated in optimal
      media, require basement membrane (Matrigel) for expression of brush border
      enzymes. Under these conditions, adding nucleotides to the culture medium
      enhanced enzyme activity. In addition to being substrates for intestinal
      absorption, nucleotides may affect enterocyte differentiation.

PMID- 8283304
TI  - Nucleotide actions on humoral immune responses.
AB  - Previous studies indicate the importance of dietary nucleotides in maintaining
      optimal cellular immunity. Our studies using murine spleen cells showed that
      polynucleotides significantly increase in vitro antibody production in response
      to T-cell-dependent antigen. They seem to exert actions on T-helper cells at
      antigen presentation, perhaps during cognitive cell-cell interactions. They do
      not augment the actions of cloned, antigen-specific, activated T-helper cells,
      nor do they increase antibody production in response to T-cell-independent
      antigen or polyclonal B-cell activation. Polynucleotides increase in vitro human
      immunoglobulin production in response to T-cell-dependent stimuli and antigen.
      Humoral immune responses to T-cell-dependent antigen were depressed in mice fed a
      nucleotide-free diet, but were restored by a mononucleotide-nucleoside mixture.
      Responses to T-cell-independent antigen remained intact in these mice. The
      mononucleotide-nucleoside mixture had no effect on in vitro antibody production
      and did not further increase humoral immune responses in mice fed regular lab
      chow. These results suggest that the in vivo actions of polynucleotides on
      humoral immune responses may reflect local immune responses, perhaps at the site
      of inflammation. Mononucleotides and nucleosides may be incorporated into the
      tissue nucleotide pool fairly rapidly in a state of relative nucleotide
      deficiency and help restore T-cell-dependent humoral immune responses. Our
      findings may further support the importance of dietary nucleotides.

PMID- 8283305
TI  - Dietary nucleotides: cellular immune, intestinal and hepatic system effects.
AB  - Investigations with animals demonstrate that dietary nucleotides influence immune
      function. Restriction of dietary nucleotides in mice decreases several indices of
      cell-mediated immunity as well as resistance to challenge with Staphylococcus
      aureus or Candida albicans. Spleen cells of mice maintained on nucleotide-free
      diet produce less interleukin-2 and have lower natural killer cell cytotoxicity
      and macrophage activation than those of animals fed nucleotide-supplemented
      diets. In vivo lymphoproliferative response, macrophage phagocytic activity and
      expression of interleukin-2 receptor and lyt1 surface marker are also lower in
      animals fed nucleotide-free diets. At 2 mo of age, infants fed breast milk or
      nucleotide-supplemented infant formula exhibit increased natural killer cell
      activity compared with infants fed unsupplemented formula. Dietary nucleotide
      restriction in animals may also result in hepatic lipid accumulation and
      decreased mucosal height and gut wall thickness. Adenosine monophosphate, a
      mediator of hepatic and small bowel blood flow, may play a unique role among the
      nucleotides studied. In conclusion, de novo synthesis and salvage of nucleotides
      is a metabolically costly process. An exogenous source of nucleotides from the
      diet may optimize the function of rapidly dividing tissues, particularly when
      growth is rapid and the diet is low in nucleotides.

PMID- 8283306
TI  - Dietary nucleotides: effects on the gastrointestinal system in swine.
AB  - Nucleotides in the intestinal lumen may decrease the inflammatory response to
      ischemia-reperfusion. In a newborn-swine model, we showed that perfusion of the
      intestinal lumen with nucleotides in concentrations similar to those in human
      milk induced hyperemia. The levels of hypoxanthine (and xanthine) were not
      increased in the presence of nucleotides during ischemia-reperfusion, and the
      number of leukocytes accumulated in the intestine was reduced in the presence of
      nucleotides. Furthermore, nucleotides may have decreased protein leak and the
      production of nitric oxide during ischemia. These effects are not changed
      significantly in the presence of an adenosine antagonist. We interpreted our
      results to indicate that the protective effects of nucleotides in the intestinal
      lumen are not due to adenosine alone.

PMID- 8283307
TI  - Nonimmune system responses to dietary nucleotides.
AB  - Studies have demonstrated that a fecal flora with a predominance of
      bifidobacteria develops in infants fed a nucleotide-supplemented commercial
      formula, closer to that in breast-fed infants. In contrast, enterobacteria
      predominate in the fecal flora of infants fed an unsupplemented formula. When
      given parenterally, nucleotides promote recovery from injuries caused by
      hepatotoxic agents. These results suggest that dietary nucleotides may
      potentially play a significant role in nutrition.

PMID- 8283308
TI  - The role of nucleotides in adult nutrition.
AB  - Dietary nucleotides, found in normal diets, have been recently determined to be
      required for normal immune defenses. Rejection of cardiac transplants, graft-vs.
      host disease, and delayed cutaneous hypersensitivity in animal models are all
      suppressed by a diet deficient in nucleotides. T lymphocytes seem to require
      dietary nucleotides for normal maturation and function. Host resistance to
      bacterial and fungal infections is decreased in mice on nucleotide free diets;
      addition of RNA or uracil prevents this vulnerability to infection. Dietary RNA
      is required to restore lost immune function after protein deprivation. Adequate
      calories and protein alone do not return immune function to normal. Dietary
      nucleotides can restore lost immune function even during protein starvation and
      weight loss. Because all parenteral and most enteral nutrient solutions are
      nucleotide free, clinical studies were undertaken comparing a new nucleotide
      containing diet (Impact) to a standard high protein enteral feeding. In two
      separate double blind clinical studies the patients fed the enteral diet
      containing nucleotides had improved immune function compared with patients
      receiving a nucleotide free diet. In addition, infectious complications and
      length of hospital stay were reduced in postoperative cancer patients fed Impact
      compared with a control group.

PMID- 8283309
TI  - Ascorbic acid deficiency reduces the level of mRNA for cytochrome P-450 on the
      induction by polychlorinated biphenyls.
AB  - Ascorbic acid (AsA) deficiency causes a decrease in hepatic concentration of
      cytochrome P-450 and a decrease in hepatic activity of drug-metabolizing enzymes
      in rats unable to synthesize AsA (ODS rats). To study the mechanism of the
      decrease in hepatic concentration of cytochrome P-450 isozymes by AsA deficiency,
      we chose the xenobiotics-inducible cytochrome P-450 and performed the experiments
      indicated below. AsA-deficient rats were fed polychlorinated biphenyls (PCB)
      which markedly induce both CYP1A subfamily and several isozymes in CYP2B
      subfamily. First, we assayed the activities of two drug-metabolizing enzymes so
      that one could be functionally distinguished from another. AsA deficiency
      significantly reduced the hepatic activity of aminopyrine-N-demethylase in ODS
      rats with and without dietary PCB, but had no effect on benzo(a)pyrene
      hydroxylase activity. Secondly, quantitative immunoblot analyses demonstrated
      that the levels of CYP2B1/2B2 and CYP1A1 in the AsA-deficiency rats fed PCB were
      approximately 60 and 80% lower than those found in rats fed AsA-supplemented
      diet. The degree of reduction in CYP2B1/2B2 was greater than CYP1A1. Thirdly, AsA
      deficiency caused a decrease in hepatic abundance of CYP2B1/2B2 mRNA, whereas it
      had no effect on the levels of CYP1A1 and 1A2 mRNA. These results indicated that
      dietary AsA selectively affects the levels of CYP2B1/2B2 mRNA among cytochrome P
      450 induced by PCB and plays important roles for optimum induction of drug
      inducible cytochrome P-450. We concluded that AsA deficiency decreases specific
      froms of drug-inducible cytochrome P-450, especially CYP2B1/2B2 and that the
      reduction of CYP2B1/2B2 mRNA level in AsA-deficient rats caused a decrease in
      cytochrome P-450 concentration and hepatic activity of drug-metabolizing enzymes.

PMID- 8283310
TI  - Influence of dietary vitamin E on the 8-hydroxydeoxyguanosine levels in rat liver
      DNA.
AB  - Rats were fed either a low vitamin E (VE) diet (-VE), a basal VE diet (+VE, 4.5
      mg%), or a high VE diet (+VE, 45 mg%) for 7 weeks. VE content, oxidative DNA
      damage and lipid peroxide levels in their livers were measured. When purified
      lard was used as a dietary fat, VE content decreased in the low VE group to one
      thirtieth of that in the basal VE group; in the high VE group it increased to 4.5
      fold that in the basal VE group. Corresponding to the VE levels, lipid peroxide
      levels increased to 2.7-fold in the low VE group and decreased to two-thirds in
      the high VE group. The level of 8-hydroxydeoxyguanosine (8-OHdG) in DNA, a marker
      of oxidative DNA damage, was about 0.6 per 10(5) deoxyguanosine in the basal VE
      group and comparable values were found in the low VE and the high VE groups. When
      either soybean oil or safflower oil was used as a dietary fat, VE content and
      lipid peroxide levels in the liver were also markedly changed in both the low VE
      group and the high VE group. 8-OHdG levels in DNA of the low VE with safflower
      oil group tended to be higher than that of the basal and high VE groups. However,
      no significant difference was observed among them. These results suggest that the
      change in VE has little influence on the level of oxidative DNA damage in the
      liver.

PMID- 8283311
TI  - Influences of some low molecular compounds on enzymatic activity and isoelectric
      point of aspartate aminotransferase from rat liver.
AB  - The substances responsible for regulating cytosolic aspartate aminotransferase
      (AspATc) activity in the cytosolic fraction of rat liver were examined. AspATc
      was removed from the cytosolic fraction by passing the fraction through an
      affinity column to which anti-AspATc antiserum was conjugated. The unbound
      fraction from the column was found to decrease the activity of the purified
      AspATc. A fraction containing compounds of less than MW 1,000 was obtained by
      filtering the cytosolic fraction through a YM 2 membrane. This YM 2 filtrate
      decreased the activity of the purified enzyme; however, the enzymic activity was
      protected partially by the addition of 2-oxoglutarate or pyridoxal phosphate
      (PLP). The YM 2 filtrate also decreased the isoelectric points (pIs) of the
      purified enzyme. Influences of glucose and fructose on AspATc were examined, and
      fructose was found to decrease the enzymic activity and the pIs. Fructose was
      more effective on apoenzyme than holoenzyme, suggesting that fructose may bind to
      the Lys258 residue of AspATc which is the binding site of PLP. The effects of
      various amino acids including substrates on the enzymic activity were also
      examined. Some amino acids were found to decrease the enzymic activity to various
      extents, though the pIs were unaltered. These results suggest that under
      physiological conditions, AspATc activity is modified by various low molecular
      substances in various ways.

PMID- 8283312
TI  - Combined effects of dietary protein and fat on lipid metabolism in rats.
AB  - The combined effects of dietary protein (casein, whey protein, or soy protein)
      and fat (safflower oil, perilla seed oil, or their mixed oil; linoleic acid/alpha
      linolenic acid = 5.0) on several lipid parameters were studied in rats. Serum
      cholesterol and triglyceride levels were lower in perilla seed oil groups
      irrespective of the protein sources. Liver triglyceride level, and fecal
      excretion of steroids were influenced mainly by protein sources, particularly
      isolated soy protein lowered liver triglyceride level, and increased the fecal
      steroid excretion. The fatty acid composition of liver phosphatidylcholine was
      influenced by dietary fat sources. The proportion of arachidonic acid was
      significantly lower in rats fed perilla seed oil than in those fed safflower oil
      or mixed oil, while the proportion of eicosapentaenoic acid was higher in rats
      fed perilla seed oil than in those fed safflower oil. Arachidonic acid/linoleic
      acid ratio was significantly lower in perilla seed oil groups, and tended to be
      higher in casein groups. Eicosapentaenoic acid/arachidonic acid ratio was
      influenced by both dietary protein and fat, and protein-fat interaction was
      observed. Eicosapentaenoic acid/arachidonic acid ratio was higher in perilla seed
      oil groups, and isolated soy protein in perilla seed oil groups lowered the ratio
      in comparison with other protein sources in perilla seed oil groups.

PMID- 8283313
TI  - Dietary Curcuma xanthorrhiza Roxb. increases mitogenic responses of splenic
      lymphocytes in rats, and alters populations of the lymphocytes in mice.
AB  - Rhizomes of Curcuma xanthorrhiza Roxb. (C. xanthorrhiza), a medicinal plant in
      Indonesia, has been shown to exert diverse physiological functions. Hitherto, a
      little attention has been paid to its effect on immune functions. This study was
      carried out to determine the effect of this medicinal plant on mitogenic response
      of splenic lymphocytes in rats and population of splenic lymphocytes and
      macrophages and peripheral blood macrophages in mice. Mitogenic responses of
      splenocytes to phytohemagglutinin, concanavalin A, and pokeweed mitogens were
      examined in rat fed C. xanthorrhiza for 3 weeks. The medicinal plant increased
      the blastogenesis to these mitogens. Flow cytometric analysis was carried out for
      mice fed the medicinal plant for 3 to 5 weeks. C. xanthorrhiza increased the
      proportion of the splenic T cells throughout the experimental period, but exerted
      a variable effect on B cells and T cell subsets, that is, elevations of B cells
      at 3 weeks and of Th cells at 4 weeks without any elevation of Ts cells. The
      effect of this medicinal plant on a proportion of macrophages from the spleen and
      peripheral blood was not consistent. Thus, the present study suggests that C.
      xanthorrhiza contains some principle(s) activating T and B cell-mediated immune
      functions.

PMID- 8283314
TI  - Imbalance of calcium, magnesium, and phosphorus in bone and other tissues of rats
      induced by low protein and calcium deficiency.
AB  - Female Wistar rats were separated into 9 groups, and 9 different synthetic diets
      (each diet contains different level of protein and calcium) were given to each
      group. After 5 weeks of these dietary regimens, all rats were sacrificed and
      calcium, magnesium, and phosphorus levels in plasma and various tissues were
      determined. In calcium-deficient groups, calcium, magnesium, and phosphorus level
      in bone decreased, plasma calcium level decreased and there was a tendency that
      magnesium levels in brain and liver and phosphorus level in brain increased. When
      comparison was made among the calcium-deficient groups, calcium, magnesium, and
      phosphorus levels in bone were higher in low protein/calcium-deficient group than
      higher protein/calcium-deficient groups. It is probable that protein deficiency
      inhibits calcium depletion and consequently the influence of calcium deficiency
      is less significant in the condition of deficiency in both protein and calcium.

PMID- 8283315
TI  - Increased 120 kDa protein in liver cytosol of genetically obese Zucker rats.
AB  - In this study, the differences between the pattern of stained proteins from
      genetically obese Zucker rats and those from lean Zucker rats were analyzed using
      SDS-polyacrylamide gel electrophoresis. The level of the 120 kDa protein in the
      liver cytosol fraction of these obese rats was several times higher than that
      found in the lean rats. This protein was not present in the mitochondrial
      fractions of either strain. The level of the 120 kDa protein was decreased
      drastically during a 72-h fast in the obese Zucker rats. An increase in the level
      of this protein was induced in the lean Zucker rats through a 48-h fast followed
      by refeeding with a high-carbohydrate diet. However, when the lean Zucker rats
      were refed with a high-fat diet following the fast, no significant change was
      observed in the level of the 120 kDa protein. These observations strongly suggest
      that the elevated levels of the 120 kDa protein seen in the liver cytosol
      fraction of obese Zucker rats may be responsible for the observed increases in
      lipogenesis and pathogenesis of obesity in these rats.

PMID- 8283316
TI  - Immunoelectron microscopic localization of lactase-phlorizin hydrolase in rat
      small intestine.
AB  - To provide insight into the intracellular translocation of lactase-phlorizin
      hydrolase, an immunoelectron microscopy was performed on rapidly embedded
      Lowicryl K4M sections of rat jejunum. Lactase-phlorizin hydrolase
      immunoreactivity was detected not only in the microvillous membranes and in the
      smooth apical vesicles, but also in the lateral membranes, suggesting an
      alternative route for intracellular transport of lactase-phlorizin hydrolase via
      the lateral membranes to the microvilli.

PMID- 8283317
TI  - Bioavailability of magnesium contained in purple laver (Asakusa-Nori) by rats
      with scarce magnesium, being evaluated from serum magnesium, kidney
      calcification, and bone magnesium contents.
AB  - An experiment was designed to evaluate the bioavailability of purple laver
      (Asakusa-Nori, Porphyra tenera Kjellman) magnesium (Mg) in Mg-scarcity Fischer
      344 male rats from serum Mg level, kidney calcification and bone Mg contents.
      Male rats of 4 weeks of age were divided into four groups of six rats. The four
      groups were control (20SC), Mg-restricted (-Mg20SC), -Mg20SC plus purple laver (
      Mg20SCP), and 20SC plus purple laver (20SCP) group respectively. To -Mg20SC, 1/10
      Mg of the 20SC diet was added. -Mg20SCP diet purple laver as a Mg source. 20SCP
      diet was designed to contain double amount of Mg. After a 3-week experimental
      period, rats were decapitated. Blood serum, right kidney, and right femur were
      collected and Mg, calcium (Ca), phosphorus (P) were determined. Serum Mg
      concentration of the -Mg20SC was 1/3 of the 20SC, indicating apparent
      hypomagnesemia. Serum P also showed lowered concentration. On the other hand, the
      serum Ca indicated higher value than the other groups, indicating hypercalcemia.
      Addition of purple laver to -Mg20SC diet resulted in a normal serum Mg, Ca, and P
      level. The Mg-scarcity (-Mg20SC) rats accumulated much amount of kidney Ca.
      Whereas, there was no significant difference in kidney Ca between control (20SC)
      group and purple laver-supplemented (-Mg20SCP) rat group. The -Mg20SC rats showed
      lowered ash content and reduced Mg and P concentrations in the femur. Purple
      laver supplementation increased the ash, Mg, and P. All of the results indicated
      that the purple laver Mg was used as a Mg source.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8283318
TI  - Facile preparation of rat intestinal mucosa for assay of mucosal enzyme activity.
AB  - Intestinal mucosa of rats was prepared by squeezing the frozen and thawed
      intestine. The method was much easier compared to the conventional method in
      which intestine was cut longitudinally or everted and mucosa was scraped. Jejunal
      mucosal weight prepared by the two methods was not different, but ileal mucosal
      weight prepared by squeezing was significantly heavier than that by scraped. No
      significant difference was observed between activity of some brush border enzymes
      (arylamidase, aminopeptidase, alkaline phosphatase, and sucrase) in mucosa
      prepared by squeezing and that by conventional scraping method in jejunum.
      Activity of brush border aminopeptidase and sucrase in ileal mucosa prepared by
      squeezing was significantly higher than that prepared by scraping.

PMID- 8283319
TI  - Effect of a glutamine-supplemented diet on response to methicillin-resistant
      Staphylococcus aureus infection in mice.
AB  - The following study was undertaken to determine whether dietary supplementation
      with glutamine can be used to modulate the immune response following challenge
      with methicillin-resistant Staphylococcus aureus (MRSA) organisms in mice. Thirty
      BALB/c female mice were randomized into 3 groups: group A (n = 10) were fed 20%
      casein diet (control), whereas the mice in Groups B (n = 10) and C (n = 10) were
      given 20% casein diet supplemented with 2 and 4% glutamine, respectively. The
      diets were made isonitrogenous by glycine and alanine supplementation. On the
      10th day on these treatments, each mouse was challenged intravenously with 2 x
      10(8) colony-forming units (CFU)/ml of MRSA organisms and mortality was noted for
      20 days. The survival rate in Group A (20%) tended to be lower than the rates in
      Group B (40%), and Group C (70%). CFU values of spleen and kidney of the
      surviving mice 20 days post challenge were not different among the three groups
      (p < 0.05). The present results suggest that dietary glutamine supplementation
      may be effective as a nutritional immunomodulator for the recovery from MRSA
      infection.

PMID- 8283320
TI  - Response of liver microsomal mixed-function oxidases to dietary linoleic acid
      levels in rats.
AB  - Responses of the activities of liver microsomal mixed-function oxidases (MFOs)
      induced by phenobarbital (PB) to dietary linoleic acid (LA) levels were
      investigated in rats. Diets varied in LA content (0, 1.8, 4.1, 7.0, or 13.8
      energy%) were fed to rats for 16 days. The activities of MFOs did not change
      significantly with increasing the dietary LA level, where they reached a plateau
      even at 1.8 energy %, although the fatty acid composition of liver microsomal
      lipids reflected well that of dietary lipids. Accordingly, 2 energy % of LA as
      essential fatty acid seemed to be sufficient to supply the dietary requirement as
      assessed by the activities of PB-induced MFOs.

PMID- 8283321
TI  - Viscoelastic shear properties of articular cartilage and the effects of
      glycosidase treatments.
AB  - The objectives of this study were to determine the viscoelastic shear properties
      of articular cartilage and to investigate the effects of the alteration of
      proteoglycan structure on these shear properties. Glycosidase treatments
      (chondroitinase ABC and Streptomyces hyaluronidase) were used to alter the
      proteoglycan structure and content of the tissue. The dynamic viscoelastic shear
      properties of control and treated tissues were measured and statistically
      compared. Specifically, cylindrical bovine cartilage specimens were subjected to
      oscillatory shear deformation of small amplitude (gamma degrees = 0.001 radian)
      over a physiological range of frequencies (0.01-20 Hz) and at various compressive
      strains (5, 9, 12, and 16%). The dynamic complex shear modulus was calculated
      from the measurements. The experimental results show that the solid matrix of
      normal articular cartilage exhibits intrinsic viscoelastic properties in shear
      over the range of frequencies tested. These viscoelastic shear properties were
      found to be dependent on compressive strains. Our data also provide significant
      insights into the structure-function relationships for articular cartilage.
      Significant correlations were found between the material properties (the
      magnitude of dynamic shear modulus, the phase shift angle, and the equilibrium
      compressive modulus), and the biochemical compositions of the cartilage
      (collagen, proteoglycan, and water contents). The shear modulus was greatly
      reduced when the proteoglycans were degraded by either chondroitinase ABC or
      Streptomyces hyaluronidase. The results suggest that the ability of collagen to
      resist tension elastically provides the stiffness of the cartilage matrix in
      shear and its elastic energy storage capability. Proteoglycans enmeshed in the
      collagen matrix inflate the collagen network and induce a tensile prestress in
      the collagen fibrils. This interaction of the collagen and proteoglycan within
      the cartilage matrix provides the complex mechanism that allows the tissue to
      resist shear deformation.

PMID- 8283322
TI  - Effects of exercise and polysulfated glycosaminoglycan on repair of articular
      cartilage defects in the equine carpus.
AB  - Our aim was to determine if mild to moderate postoperative exercise and intra
      articular polysulfated glycosaminoglycan result in improved repair of large,
      experimentally induced osteochondral defects in a weight-bearing surface of
      equine joints. Arthroscopic debridement was used to produce full-thickness
      defects in a weight-bearing area of the radial carpal bones in 18 ponies. The
      ponies were randomly assigned to two groups balanced for age: nine animals in the
      exercise and nine in the no exercise group. Six ponies in each group were
      medicated weekly for 5 weeks with an intra-articular injection of polysulfated
      glycosaminoglycan in one middle carpal joint beginning at the time of operation.
      Walking (twice daily) was begun 6 days postoperatively, and by the twelfth week
      postoperatively the ponies were trotting for 25 min and walking for 15 min twice
      daily. At the time of the ponies' death, 17 weeks postoperatively, each defect
      had an average of 50-75% coverage with repair tissue. Exercised, medicated joints
      had a significantly smaller area of coverage with repair tissue than exercised,
      nonmedicated joints. Cartilaginous repair tissue from exercised ponies contained
      significantly more glycosaminoglycan and type-II collagen (r = 0.53, p < 0.05).
      The ratio of hydroxylysine to hydroxyproline was significantly lower and the
      ratio of collagen content to total protein was significantly higher in the repair
      tissue of medicated joints than in the repair tissue of nonmedicated joints; this
      is consistent with the presence of less type-II collagen in the repair tissue in
      medicated joints. We concluded that postoperative exercise was beneficial and
      that the immediate postoperative use of intra-articular polysulfated
      glycosaminoglycan was detrimental to the development of cartilaginous repair
      tissue in large osteochondral defects of equine joints.

PMID- 8283323
TI  - Knee joint contact pressure decreases after chronic meniscectomy relative to the
      acutely meniscectomized joint: a mechanical study in the goat.
AB  - Several studies have shown that meniscectomy causes an immediate, acute increase
      in knee joint contact pressure and that changes in pressure distribution cause
      remodeling of bone and soft tissue. Presumably, this remodeling in turn affects
      contact pressures. This study tested the hypothesis that medial compartment
      contact pressure increases immediately after medial meniscectomy and then
      decreases with time. Supporting hypotheses regarding medial compartment contact
      area and lateral compartment pressures also were tested. Unilateral medial
      meniscectomy was performed on seven adult goats. Four or 8 months later, contact
      pressure and area were measured in vitro in the involved joints, as well as in
      the contralateral joints, before and after removal of the meniscus. The medial
      compartment pressures of the chronically meniscectomized joints were
      significantly less than those of the acutely meniscectomized paired joints but
      remained significantly greater than those of the intact joints. For the 4 and 8
      month groups combined, the mean pressures of the acutely and chronically
      meniscectomized joints were greater than the pressures of the paired intact
      joints by 70 and 42%, respectively. The mean medial compartment contact areas of
      the acute and chronic joints were lower than those of the intact joints by 60 and
      50%, respectively; mean lateral compartment pressures remained the same. This
      study indicates that joint remodeling reduces joint contact pressures. It also
      suggests that the effectiveness of a treatment to reduce pressure concentrations
      may be determined only by comparison, at the same postoperative time, of the
      pressure with that of the chronically meniscectomized joint, since pressures
      decreased with time without treatment.

PMID- 8283324
TI  - Duration of pain and muscular adaptations in patients with dysfunction of the
      cervical spine.
AB  - Biopsies of the sternocleidomastoid and omohyoid muscle were taken from 24
      patients who underwent arthrodesis for cervical dysfunction of different
      etiologies. The two muscles, which are involved differently in movements of the
      head and cervical spine, were investigated histochemically. Muscle fibers were
      classified as type I, IIA, IIB, or IIC (transitional fibers) according to the pH
      lability of myofibrillar ATPase and calculated relative distribution. In both
      muscles, fiber transformations (as evidenced by an increase in the relative
      amount of type-IIC fibers) were regularly observed within the first 2 years after
      the onset of the symptoms. The occurrence of the transformation processes was
      independent of the patient's age and sex and was the same for the different
      etiologies. Since the overall fiber composition of the muscles remained
      essentially unchanged, the fiber transformations must occur alternatingly in both
      directions (from "slow" to "fast" and the reverse). Muscles of patients with a
      long case history showed no greater signs of fiber transformation. Therefore,
      fiber transformations in response to cervical dysfunction occur in the initial
      stage of the disease and involve different types of muscles. The muscles then
      return to a "stable" condition, independent of the continuation of the
      dysfunction and the chronic neck pain.

PMID- 8283325
TI  - Electromyographic studies of the lumbar trunk musculature during the generation
      of low-level trunk acceleration.
AB  - An understanding of how the support mechanisms of the spine behave during lifting
      may yield insight into the loading of the spine under occupational conditions and
      help shed light on the etiology of low-back disorders. Previous controlled
      laboratory studies of spinal loadings have been limited to isometric and
      isokinetic conditions. To evaluate the behavior of the trunk during acceleration,
      we recorded intra-abdominal pressure and trunk muscle activities during low-level
      acceleration. Twenty subjects performed controlled accelerations of the trunk
      under different trunk loading conditions. Muscle activity decreased as
      acceleration increased; however, the rate of decrease differed among muscles
      (mean decrease, < or = 1% of maximum per 10 degrees/s2 increase in acceleration),
      with the activity of the erector spinae muscles decreasing the most (1.88% of the
      maximum per 10 degrees/s2 increase in acceleration). No changes in intra
      abdominal pressure were found as a function of acceleration. Relative
      coactivation of the muscles increased; however, this was a function of increases
      in trunk velocity and torque.

PMID- 8283326
TI  - Effects of local compression on peroneal nerve function in humans.
AB  - A new apparatus was developed to compress the anterior compartment selectively
      and reproducibly in humans. Thirty-five normal volunteers were studied to
      determine short-term thresholds of local tissue pressure that produce significant
      neuromuscular dysfunction. Local tissue fluid pressure adjacent to the deep
      peroneal nerve was elevated by the compression apparatus and continuously
      monitored for 2-3 h by the slit catheter technique. Elevation of tissue fluid
      pressure to within 35-40 mm Hg of diastolic blood pressure (approximately 40 mm
      Hg of in situ pressure in our subjects) elicited a consistent progression of
      neuromuscular deterioration including, in order, (a) gradual loss of sensation,
      as assessed by Semmes-Weinstein monofilaments, (b) subjective complaints, (c)
      reduced nerve conduction velocity, (d) decreased action potential amplitude of
      the extensor digitorum brevis muscle, and (e) motor weakness of muscles within
      the anterior compartment. Generally, higher intracompartmental pressures caused
      more rapid deterioration of neuromuscular function. In two subjects, when in situ
      compression levels were 0 and 30 mm Hg, normal neuromuscular function was
      maintained for 3 h. Threshold pressures for significant dysfunction were not
      always the same for each functional parameter studied, and the magnitudes of each
      functional deficit did not always correlate with compression level. This variable
      tolerance to elevated pressure emphasizes the need to monitor clinical signs and
      symptoms carefully in the diagnosis of compartment syndromes. The nature of the
      present studies was short term; longer term compression of myoneural tissues may
      result in dysfunction at lower pressure thresholds.

PMID- 8283327
TI  - Response of peripheral nerve to cyclic compression in a laboratory rat model.
AB  - Repetitive cyclic loading of a nerve has been proposed as a pathogenic factor in
      the development of occupational compression neuropathies. Little is known about
      the basic response of peripheral nerve to cyclic compression. We investigated the
      hypothesis that cyclic compression is more detrimental to nerve function than
      constant compression. We measured the amplitudes and velocities of distally
      evoked action potentials in the presence of constant or cyclic compression of the
      tibial nerve in rats. Seven groups were subjected to constant or cyclic
      compression for 6 h by a computer controlled, hydraulically activated compression
      chamber. Nerves were compressed with 0 (control group), 30, 60, or 90 mm Hg of
      constant pressure or 0-30, 20-50, or 30-60 mm Hg of cyclic compression for
      approximately 20,000 compression cycles. Action potentials were recorded every 15
      min. The effects of cyclic compression on nerve conduction were equivalent to the
      effects of constant compression at the average applied pressure. Cyclic loading
      itself does not appear to be an important pathogenic factor in the development of
      nerve conduction block.

PMID- 8283328
TI  - The effects of acidosis and alkalosis on long bone vascular resistance.
AB  - This study used an ex vivo perfusion model to investigate the direct effects of
      acidosis and alkalosis on the vascular resistance of the canine tibia. Baseline
      vascular resistance (BVR) and the vascular smooth muscle response to bolus doses
      of norepinephrine (NE) (0.025-3.2 nmol) and periarterial sympathetic nerve
      stimulation (NS) (10-25 Hz: 9 V, 2 ms pulses, 10 s) were studied. In Group I,
      these parameters were measured at normal pH (duration 7.34-7.44) and then during
      acidosis (pH 7.2-7.33). In Group II, they were measured at normal pH and then
      during alkalosis (pH 7.47-7.58). In Group III (control), they were measured
      serially at a normal pH. Alkalosis increased BVR by 56% (p < 0.0001). Acidosis
      attenuated (18% reduction) and alkalosis enhanced (66% increase) the
      vasoconstrictor action of NE (p < 0.0001). Acidosis also attenuated (11%
      reduction) the effect of sympathetic NS (p = 0.012). It is concluded that
      perfusion pH influences the sensitivity of long bone resistance vessels to
      circulating NE and sympathetic NS. Thus, local concentration of hydrogen ions may
      provide bone with a mechanism to autoregulate blood flow.

PMID- 8283329
TI  - Preservation of bone graft vascularity with the University of Wisconsin cold
      storage solution.
AB  - The preservation of the microcirculation of bone has been evaluated with use of
      an in vitro canine tibia perfusion model. The production of relaxing factors by
      the osseous vascular endothelium was used as a metabolic marker for viability.
      This endothelial eccrine function was preserved for 5 days (120 h) by cold
      storage without continuous perfusion after a washout with the University of
      Wisconsin (UW) solution. This synthetic perfusate was superior to Krebs Ringer
      solution (p < 0.05), but storage without perfusion failed to prevent a
      significant rise in vascular resistance. Two techniques were effective for the
      preservation of bone vascularity for 24 h: washout with UW solution followed by
      nonperfusion cold (4 degrees C) storage, and vascular washout with mannitol
      solution followed by continuous hypothermic (5 degrees C) microperfusion (0.03
      ml/min) with UW solution. The most consistent, and lowest, vascular resistance
      was produced by the microperfusion technique. However, UW solution does not
      consistently prevent an increase in vascular resistance with hypothermic
      ischemia. This technique may prove useful for the preservation of vascularized
      bone grafts, but it needs to be evaluated in a transplantation model.

PMID- 8283330
TI  - Localized hyperthermic treatment of experimental bone tumors with ferromagnetic
      ceramics.
AB  - Localized hyperthermic treatment was carried out with use of a metastatic bone
      tumor model in rabbits. The experimental bone tumor was created by
      transplantation of pieces of tumor line VX2 into the medullary canal of rabbit
      tibiae. Two weeks after the transplantation, a ferromagnetic ceramic pin was
      inserted in the medullary canal. Then, hyperthermia (HT) of the tumor was
      accomplished with use of an alternating magnetic field for 50 min. All the
      rabbits were killed 5 weeks after tumor transplantation, and the therapeutic
      effect was evaluated histologically and roentgenographically. Almost all the
      tumor cells within the bone marrow were killed by this procedure. The area of
      tumor necrosis in the HT group was significantly larger than in the control
      group. The pathological fracture rate and displacement rate were reduced
      significantly by this treatment (38.5 and 0%) compared with the controls (92.3
      and 92.3%). Therefore, HT with the use of ferromagnetic ceramics was effective
      for local control of malignant bone tumors and seems to be a promising new method
      of treatment.

PMID- 8283331
TI  - A method for production and characterization of metal prosthesis wear particles.
AB  - The wear of joint prostheses generates wear particles that produce an
      inflammatory response in the surrounding tissues and may contribute to bone
      resorption resulting in prosthetic loosening. Although the effects of particles
      produced from prosthetic materials have been studied extensively in vitro and in
      vivo, little attention has been paid to the standardisation of methods for the
      generation and characterization of these particles. This paper describes a
      reproducible method for generation of metal particles by the abrasive shaking of
      joint replacement components. Particular attention was given to the production of
      metal particles that closely resembled particles found around solid and loose
      human prostheses. To achieve this, particle size, size distribution, chemical
      composition, and shape were characterized. Particles that were 0.5-3.0 microns in
      diameter were isolated by differential sedimentation, and the distribution of
      particle sizes was determined with use of a Coulter Multisizer. Chemical
      composition was measured by atomic absorption spectrophotometry, and transmission
      electron microscopy was used to characterize particle shape. The techniques were
      shown to be reproducible, since there was little variation between batches over a
      lengthy time period. These or similar methods of particle production and
      characterization should be an essential part of future in vitro and in vivo
      studies of wear particles.

PMID- 8283332
TI  - Reduction of fretting corrosion of Ti-6Al-4V by various surface treatments.
AB  - Titanium and titanium-6% aluminum-4% vanadium (Ti-6Al-4V) are known to be
      biocompatible and corrosion resistant. However, there have been numerous reports
      of elevated tissue levels of titanium due to passive dissolution, wear, or
      fretting corrosion of implants. Studies were undertaken to determine whether the
      fretting corrosion of Ti-6Al-4V could be reduced by surface treatment of one or
      both surfaces in a fretting situation. Three different surface treatments were
      studied: ion implantation, physical vapor deposition nitriding, and plasma ion
      nitriding. The specimens used were screws fretting against the countersinks of a
      two-hole plate. Fretting corrosion was assessed by weight loss, by chemical
      analysis of test solutions, and by scanning electron microscopy. Surface
      treatment of one component, the screws, resulted in reduction in the release of
      titanium to only 18-32% of that seen with the untreated controls. Weight loss of
      the untreated plates fretted against physical vapor deposition nitrided screws
      and plasma ion nitrided screws was reduced to 31 and 38% of the control,
      respectively. The weight loss of plasma nitrided screws was only 30% that of the
      control. Nitriding of both plates and screws resulted in a further decrease in
      plate weight loss and metal release. Plasma ion nitriding of both components had
      the most significant effect, with the weight loss and titanium release being only
      11 and 2% of the control values, respectively.

PMID- 8283333
TI  - Stress-generated potentials in bone: effects of bone fluid composition and
      kinetics.
AB  - It is now generally accepted that stress-generated potentials (SGPs) at low
      frequencies are due to an electrokinetic phenomenon in the small interior
      surfaces of bone and are directly proportional to the zeta potential, a property
      of the poorly characterized bone surface-bone fluid interface. We hypothesized
      that this interface would be labile and might explain the controversy over
      whether or not the polarity of SGPs can invert under certain conditions. In this
      paper, the effects of alterations in the steeping fluid on SGPs for 87 samples
      from 15 animals were examined in four-point bending for steeping times of < or =
      65 h. Calcium and fluoride in distilled-deionized water and constant ionic
      strength solutions produced concentration-dependent inversions in the SGP sign. A
      new steady state was reached in approximately 18 h. The effects of the fluoride
      anion (unlike the calcium cation) apparently were reversible. The results
      strongly suggest that the zeta potential at the labile bone surface-bone fluid
      interface can undergo dramatic changes, not only in magnitude but also in sign.
      The results further suggest that the preparation of bone samples is critical to
      the understanding of this interface in vivo, and they support the hypothesis that
      SGPs have a role in bone remodeling.

PMID- 8283334
TI  - Effects of parathyroid hormone-related peptide on chick growth plate
      chondrocytes.
AB  - Parathyroid hormone-related peptide (PTHrP) and parathyroid hormone (PTH) have
      similar biological effects in vitro that are mediated through the PTH receptor.
      PTH receptors have been demonstrated in the zone of provisional calcification and
      the hypertrophic zone of the cartilaginous growth plate. The current study
      examined the biological effects of PTHrP on chick growth plate chondrocytes.
      Chondrocytes were exposed to varying doses of PTHrP for 24 h, and the
      incorporation of radioactive thymidine into DNA was used as an index of
      proliferation. A dose-dependent stimulation of proliferation was seen, with a
      maximal 27-fold increase at 50 nM PTHrP. A dose-dependent stimulation of cAMP was
      seen, with a maximal effect at a dose of 50 nM. Proteoglycan synthesis, measured
      by incorporation of radioactive sulfate, was stimulated, with a maximal effect of
      65% at 1 nM. Collagen synthesis and alkaline phosphatase activity from both
      cellular and matrix vesicle sources decreased in a dose-dependent fashion, with a
      maximal inhibition of approximately 50% of the control value. The physiologic
      significance of the PTH and PTHrP-responsiveness of growth plate chondrocytes is
      uncertain at the present time. It is possible that PTH or PTHrP, or both, act as
      a systemic, developmental modulator of cellular proliferation and differentiation
      in the growth plate.

PMID- 8283335
TI  - Experimental model in vivo for quantitative assessment of bone resorption
      inhibition.
AB  - Quantitative assessment of bone resorption inhibition in vivo is not easily
      accomplished; methods relying on a count of osteoclasts are questionable, and
      histomorphometric evaluation of the bone mass presents several technical problems
      as well. The authors developed a simple method to measure the inhibition of bone
      resorption by study of the proximal tibial metaphysis of growing rats: the height
      of the perichondrial bone ring was taken as an index of the balance between
      osteoblastic and osteoclastic activity because any agent that inhibits
      osteoclasts (without interference with osteoblasts) produces an increase in the
      height of this anatomical structure. Since the ring is well demarcated by
      surrounding tissues, its height can be measured with accuracy and used for
      quantitative assessment of bone resorption inhibition. This model was tested with
      salmon calcitonin, and it provides evidence in vivo that this hormone inhibits
      osteoclastic bone resorption.

PMID- 8283336
TI  - Achilles tendon healing: a correlation between functional and mechanical
      performance in the rat.
AB  - The pathogenesis and treatment of rupture of the Achilles tendon remain a source
      of controversy. This study presents the results of a biomechanical, functional,
      and morphological evaluation of a group of rats that had division and repair of
      the Achilles tendon. A total of 46 rats were used: 18 for biomechanical testing,
      18 for functional evaluation, and 10 for histology. Morphological examination
      revealed an early inflammatory response with loose connective tissue formation
      that was replaced gradually by fibroblasts and a collagenous matrix. The
      functional evaluation (Achilles functional index [AFI]) was made from
      measurements of the hind pawprints of walking rats. Division and repair of the
      Achilles tendon produced a significant functional impairment (mean [+/- SEM] AFI
      = -87 +/- 8; p < 0.001), which gradually improved with healing time. The load to
      failure for the repaired tendons consistently improved with healing time, in a
      manner similar to the functional recovery. The average deformation
      (repair/control) varied considerably and was not related to healing time. The
      stiffness of the repaired tendons increased with healing time and was 60% of the
      corresponding control side by day 15. The major finding of this study was a
      strong correlation between the AFI and the failure load of the healing tendon
      bone constructs (250-300 g group, r = 0.97, p < 0.001; 325-375 g group, r = 0.96,
      p < 0.001).

PMID- 8283337
TI  - [Gas ventilation through middle ear mucosa].
AB  - The possible effects of gas ventilation via the middle ear mucosa on middle ear
      pressure changes with N2O inhalation were studied. Sixty-seven ears without
      otologic problems were selected from among cases undergoing ENT surgery under
      general anesthesia. Anesthesia was induced by isoflurane or sevoflurane, and
      inhalation with a gas mixture of 21/min O2 and 31/min N2O was started under
      controlled respiration via endotracheal tube. Middle ear pressure was measured
      each minute with tympanometry just before and during N2O inhalation. Changes in
      pressure were plotted against time on an X-Y plotter, and the rate of middle ear
      pressure change and pressure change in 10 minutes were calculated. The following
      results were obtained; 1. In all cases, the middle ear pressure rose with N2O
      inhalation. However, the same concentration of N2O created different middle ear
      pressure changes in different individuals varying from 1.6 mmH2O to 107.8 mmH2O
      per minute. 2. The rate of middle ear pressure elevation tended to be greater in
      younger subjects, especially in children aged 4 to 7. 3. There was a negative
      correlation between the middle ear pressure change and pneumatization of the
      middle ear. 4. Sex, pulmonary function, and the N2O expiratory flow concentration
      did not contribute to the variability in the rate of the middle ear pressure
      elevation.

PMID- 8283338
TI  - [Congenital nasal stenosis--new concept and its cases].
AB  - Congenital nasal stenosis is a new disease concept which was reported, for the
      first time, by Knegt-Junk et al in 1988. The authors experienced 10 cases of this
      disease from 1986 to 1990. Radiography revealed that transverse width of the bony
      nasal passage of these patients was smaller than that of normal infants. Infants
      with nasal stenosis showed respiratory distress after birth and half of them had
      a low body weight and/or other congenital defects. Our patients were treated by
      nasal or oral intubation or by installation of nasal vasoconstrictor into the
      nasal passage. Four cases showed improvement up to 4 months of age, 6 others
      after 6 months of age. Tracheostomy was performed in one case. We must
      differentiate this disease from incomplete choanal atresia or nasal aperture
      stenosis. Our cases were similar to that of Knegt-Junk et al. We speculate that
      the congenital origin of this disease stems from a disturbance in embryologic
      development of the middle third of the face. Accordingly, we measured the
      diameter of the nasal passage radiography and recognized a narrow transverse
      width in the bony portion of the nose.

PMID- 8283339
TI  - [Scanning electron microscopic study on inner ear barotrauma: in the guinea pig
      with one eustachian tube occluded].
AB  - In order to investigate the mechanism of inner ear barotrauma, guinea pigs, with
      one eustachian tube occluded, were subjected to compression and decompression
      between 1 absolute pressure and 2 absolute pressures in a high pressure chamber.
      The authors divided the animals into three groups according to the speed of
      compression and decompression. Each group contained 10 guinea pigs. Morphological
      changes in the cochlear sensory hairs were examined by means of scanning electron
      microscope. On the occluded side, hair cells were damaged more frequently and
      more severely by rapid compression than by rapid decompression. There was no
      difference in the degree of damage produced by slow decompression and rapid
      decompression. On the control side, slight or moderate damage to hair cells was
      observed mainly as a result of rapid decompression. These findings led us to
      hypothesize that, in the setting of normal eustachian tube function, inner ear
      barotrauma would generally be caused by the relative positive pressure in the
      middle ear cavity that occurs during decompression. Furthermore, animals deprived
      of eustachian tube function would not have sufficient endurance for rapid
      compression and would sustain inner ear barotrauma far more readily, and of far
      greater severity, with rapid compression than would animals with normal
      eustachian tube function. The difference may be due to the presence of another
      pressure transmission pathway to the inner ear. The mechanism of cochlear sensory
      hair damage due to atmospheric pressure changes is presumed to be distortion of
      the reticular lamina and cuticular plate caused by the difference in pressure
      between cortilymph (perilymph) and the subtectorial space (endolymph) resulting
      in injury to stereocilia.

PMID- 8283340
TI  - [Age-dependent changes in the square drawing test].
AB  - The square drawing test (SDT) is vertical writing test, conducted to evaluate
      equilibrium, done with the subject blindfolded. We investigated the development
      of equilibrium and presbyastasis by using SDT. Fifty three children underwent SDT
      every year for nine years (5-14 years old). Sixty six healthy elderly subjects
      (65-88 years old) were also examined. Control results were obtained from 117
      young adults (22-33 years old). Four parameters of SDT (the total of each length,
      the whole length, the deviation angle and the start-end distance) were calculated
      with an SDT-computer and subjected to statistical analysis. Through the seventh
      grade, at least one of the parameters of SDT was statistically different from
      that in young adults. These differences were not observed in eighth grade
      children. Most parameters of SDT in elderly subjects were statistically different
      from those of control subjects. These results suggest that the equilibrium
      function matures at approximately 14 years of age and is commonly impaired after
      65 years of age.

PMID- 8283341
TI  - [Transsubmucosal maxilloethmoid sinus surgery through inferior turbinate
      (swinging of nasolacrimal duct and inferior turbinate)].
AB  - We recently devised a new technique for endonasal surgery, which simplifies
      maxillary antrotomy and ethmoidectomy, and dilates the middle nasal meatus widely
      enough to allow easier postoperative observation. Surgery is initiated by an
      incision similar to the one used for submucosal resection of the inferior
      turbinate. The bony inferior turbinate is resected, and the nasolacrimal duct is
      freed from the bone. Subsequently, the maxillary and ethmoidal sinuses are
      excenterated, with swinging of the membranaceous inferior turbinate and the
      nasolacrimal duct. Postoperative observation confirmed satisfactory results.

PMID- 8283342
TI  - [Quantitative evaluation of X-ray opacity of the maxillary sinus using a digital
      disposition system].
AB  - The authors attempted to obtain a quantitative index of X-ray opacity of the
      maxillary sinus using a digital disposition system. X-ray films of the Waters'
      view were used for analysis. A cooper wedge was placed on the left side of the
      subject's face and was simultaneously filmed. The wedge was made of copper plates
      increased in thickness from 0.2 to 4.0 mm in 20 steps and serving as a
      calibration standard. The subject-to-film distance was kept constant at one
      meter. The voltage and current of the X-ray tube were 85 kV and 200 mA,
      respectively. The X-ray films were digitized with a film-digitizer (Toshiba, TDF
      500B). The X-ray opacity from 0.0 to 4.0 was transformed to 1024 steps and the
      whole X-ray film was divided into 512 x 512 pixels. Then, the X-ray density of
      each pixel was converted to an absolute value of wedge thickness with a medical
      image processor (Toshiba, GMS-500U). The mean pixel values in the region of
      interest (ROI) of the maxillary sinus and that of the whole maxillary sinus were
      named MR and MW, respectively. The mean pixel value in the ROI of the ipsilateral
      orbita was called O. We used MR, MW, MR -O and MW -O as indices. The results were
      as follows: 1. MR, MW, MR -O and MW -O were useful in quantitative evaluation of
      the X-ray opacity of the maxillary sinus in a subject. 2. MR -O and MW -O were
      also good references for comparing the X-ray opacity of the maxillary sinus among
      different subjects.

PMID- 8283343
TI  - [Immunohistological study of eosinophilic infiltration of nasal polyps in aspirin
      induced asthma].
AB  - It is well known that nasal polyps frequently develop in patients with aspirin
      induced asthma, which is thought to be a non-atopic disease. We
      immunohistochemically examined the eosinophils infiltrating the nasal polyps in
      patients with aspirin-induced asthma. It has also been established that the
      monoclonal antibody EG1 reacts with both stored and secretion type ECP
      (eosinophil cationic protein), and that EG2 reacts only with the secretion type
      of ECP. EG2 positive cells may thus be considered to be activated eosinophils.
      Seven cases with nasal polyps associated with aspirin-induced asthma participated
      in our study. Blood eosinophilia was observed in all 7 cases, but 6 showed normal
      blood values IgE. Two reacted to house dust antigen, on skin tests and RAST. In
      the nasal polyps, many EG2 positive cells were observed. On serial sections, the
      number and distribution of EG1 and EG2 positive cells were almost equal. In the
      superficial lamina propria, extra-cellular release of ECP was noted. However,
      epithelial damage did not relate to the number of EG2 positive cells or the
      degree of extra-cellular EG2 release. In the deep lamina propria, slight extra
      cellular ECP release was found. From these results, the eosinophils in nasal
      polyps accompanying aspirin-induced asthma were thought to be activated.
      Eosinophils seem to play an important role in the development of nasal polyps.
      However, tissue injury induced by eosinophils, was not be demonstrated in this
      study.

PMID- 8283344
TI  - [Functional and pathohistologic changes in an ischemic model of rat inner ear].
AB  - We investigated functional and histopathological changes in the inner ear
      circulatory disorder caused by thrombosis of the anterior inferior cerebellar
      artery (AICA) in rats. The thrombosis was induced by a photochemical reaction
      between green light and systemic injection of Rose Bengal. During this
      experiment, auditory brainstem responses (ABR) were recorded and cochlear blood
      flow (CBF) was measured by a laser doppler flowmeter. Within 5 weeks after the
      procedure, histopathological changes were studied by light microscopy following
      the observation of equilibrium dysfunction and ABR recording. CBF was reduced
      from the baseline in 30.8 +/- 3.4% (mean +/- SE, n = 25) by occlusion of the
      AICA, ABR was altered in 96% of animals, and equilibrium dysfunction was observed
      in 77%. When the AICA was not reopened within a short time, severe
      histopathological changes were frequently observed. There was no significant
      correlation between equilibrium dysfunction and histopathological changes in the
      vestibule. It is concluded that this experimental model may be useful for
      investigating functional and histopathological changes in the ischemic inner ear.

PMID- 8283345
TI  - [Relationship between external auditory canal temperature and caloric nystagmus-
      the problem with the ordinary cold-warm caloric test].
AB  - The cold-warm caloric test is performed with water irrigation, using a hot
      temperature of 44 degrees C and a cold temperature of 30 degrees C, which are
      thermally equidistant from the body temperature 37 degrees C. However, the 30
      degrees C irrigation nearly always produces a stronger nystagmic response than
      that of the 44 degrees C stimulation. The purpose of this study is to investigate
      the difference in nystagmic response between cold and hot stimulation. The
      achieved hot (44 degrees C) and cold (30 degrees C) water samples were prepared,
      and irrigation was with a disposable plastic syringe. Temperature changes in the
      external auditory canal were monitored by tympanic thermometry during the cold
      warm caloric test. Maximal slow phase velocity and the duration of induced
      nystagmus were recorded on an electro-nystagmograph. The following conclusions
      were drawn; 1) The average normal external auditory canal temperature was 36.8
      degrees C, and there was no side difference between the right and left ears.
      External canal temperature was higher than that of the axilla. 2) When 20 ml of
      30 degrees C water was instilled the temperature change in the external canal was
      larger than that in response to the 44 degrees C water and the maximal slow phase
      velocity of nystagmus for cold stimulation was stronger than that for hot.
      However, the duration of nystagmus for the cold was not significantly longer than
      that of the hot stimulation.

PMID- 8283346
TI  - [Combined-macro-micro endoscopic technique as the most advantageous endonasal
      sinus surgery especially for severe sinusitis: theory and surgical technique].
AB  - Functional endonasal sinus surgery (FESS) is becoming the procedure of choice for
      the surgical treatment of chronic sinusitis. The operation has been made possible
      by the introduction of the endoscope to sinus surgery. The endoscope allows a
      more detailed observation of ethmoid lesions, and provides direct visual access
      to the paranasal region which is not visible through the anterior nares. A
      technique which involves the exclusive use of endoscopy, endoscopic sinus
      surgery, presents several problems however, especially in cases of polyposis or
      those with excessive bleeding. For ideal sinus surgery, tools must guarantee the
      greatest possible safety, ease, and accuracy. None of the currently available
      tools is independently able to fully satisfy all three of these requirements, not
      even the endoscope. The anatomical region being operated on determines which of
      these three requirements is most critical in each phase of the surgery. Ease is
      most important in the nasal cavity, which has no exceptionally dangerous regions
      to be operated on. The quickest and simplest operation is most expedient for
      minimizing blood loss in severe polyposis. To achieve this objective, macroscopic
      manipulation using a headlamp is most suitable. There is no need to use the
      endoscope or microscope to remove polyps in the nasal cavity. Because almost all
      of the risks in sinus surgery are encountered in the ethmoid region, operation in
      this area demands the safest method. For example if the ethmoid cavity is filled
      with massive polyps, it is sometimes difficult to endoscopically detect whether
      orbital fat has broken into the ethmoid. To discriminate between fat and a
      polypoid lesion or to distinguish dura from mucoperiost during surgery, the
      microscope is clearly the superior tool. In region where dead angles prevent
      accurate manipulation, use of the endoscope is essential. To optimize success in
      sinus surgery using the currently available tools, the author describes a
      combined macro-micro-endoscopic technique (COMMET) which effectively combines use
      of the headlamp, the microscope, and the endoscope according to the demands of
      each anatomical region.

PMID- 8283347
TI  - [Morphological changes in the supporting cells of the utricular macula due to
      streptomycin intoxication].
AB  - Morphological changes in cultured utricular supporting cells following
      streptomycin sulfate (SM) intoxication were investigated using an organ culture
      system. Utricles of guinea pig were exposed to 30 and 3mg/ml of SM for 1-3 days
      in culture. The number of lysosomes in the supporting cells increased daily, and
      mitochondria, myeloid bodies, granules and vesicles were observed within the
      lysosomes. As these components accumulated in the lysosomes, the number of
      granules and vesicles in the cytoplasma decreased. Acid phosphatase (AcPase)
      activity also decreased. After 1-3 days culture with SM, the culture medium was
      changed to a medium without SM. After removal of SM, the Golgi apparati appeared
      more developed and AcPase activity was higher. At the same time, lysosomes were
      markedly decreased in number and the endoplasmic reticulum showed a gradual
      reproduction. These findings suggest close relationships among the Golgi
      apparatus, lysosomes, secretory granules and the endplasmic reticulum.

PMID- 8283348
TI  - Genetic alterations of the TP53 gene, p53 protein expression and HPV infection in
      primary cervical carcinomas.
AB  - Primary cervical carcinomas from 92 patients were investigated for genetic
      alterations in the tumour suppressor gene TP53. Studies of allelic imbalance (AI)
      were performed by Southern blot analysis and by using two PCR (polymerase chain
      reaction) polymorphisms within the TP53 gene. AI in the tumour was observed in 22
      per cent (11 of 52 informative patients) and was significantly associated with
      recurrence both in a univariate (P = 0.013) and in a multivariate (P = 0.045)
      analysis. The DNA samples were subjected to mutation analysis of four of the
      conserved domains in the TP53 gene, using PCR followed by constant denaturant gel
      electrophoresis (CDGE). Mutations were observed in 2 of 92 tumours (2 per cent),
      of which one was a silent mutation and the other a frameshift. Overexpression of
      the p53 protein was found by immunostaining of sections from formalin-fixed,
      paraffin-embedded material in 55 per cent (51/92) of the tumours. In 88 per cent
      (45/51) of these, overexpression was present in less than 5 per cent of the
      tumour cells. Overexpression was significantly associated with relapse-free
      survival only in a univariate analysis (P = 0.045). AI of the TP53 locus did not
      correlate with p53 expression or mutation. The important gene on 17p, responsible
      for the shorter disease-free survival for patients with AI of TP53, may therefore
      be another gene closely linked to TP53. In addition, the 92 tumour samples were
      tested for the presence of human papillomavirus (HPV) types 16 and 18. Fifty-four
      per cent (50/92) of the samples were positive for HPV 16 using in situ
      hybridization, and 93 per cent (86/92) using the PCR technique. The numbers for
      HPV 18 were 15 per cent (14/92) and 23 per cent (21/92), respectively. Twenty-one
      per cent (19/92) were positive for both HPV 16 and HPV 18, while 4 per cent
      (4/92) were negative for both HPV 16 and 18. The tumour with the frameshift TP53
      mutation was HPV 16-positive, and the four samples negative for HPV 16 and 18 did
      not contain TP53 mutations within the conserved domains but had elevated p53
      protein expression.

PMID- 8283349
TI  - Expression of the pS2 peptide in primary breast carcinomas: comparison of
      membrane and cytoplasmic staining patterns.
AB  - The pS2 protein is oestrogen-regulated in breast cancer cell lines. Previous
      studies have shown a relationship to oestrogen receptor in primary breast
      carcinomas. This study examined 178 breast carcinomas for pS2 using
      immunohistochemistry. A high frequency (77 per cent) of positive tumours was
      found, using a 10 per cent cut-off point to define a positive tumour. There was
      no relationship with menopausal status or node status, a significant association
      with differentiation, a weak association with oestrogen receptor, and no
      association with progesterone receptor or overall survival. Two patterns of
      cellular localization were observed: cytoplasmic and membrane. The former showed
      a stronger relationship with oestrogen receptor status, although there were
      oestrogen receptor-negative tumours with marked pS2 staining. Membrane staining
      showed a stronger relationship with differentiation, with a staining pattern
      similar to that observed for milk fat globule membrane. The staining patterns
      observed may support a role for pS2 in a secretory mechanism. However, the
      expression and function of pS2 in breast carcinomas remain complex, and are not
      simply related to oestrogen regulation.

PMID- 8283350
TI  - Demonstration of light chain mRNA in Hodgkin's disease.
AB  - The lineage of Hodgkin and Reed-Sternberg cells is still unclear. Detection of
      both immunoglobulin light chains in Hodgkin and Reed-Sternberg cells by
      immunohistochemistry is a well-known phenomenon. However, up to now, in situ
      hybridization techniques have failed to demonstrate light chain messenger(m) RNA
      in Hodgkin and Reed-Sternberg cells. In this investigation, we have analysed 26
      cases of Hodgkin's disease (nodular lymphocyte predominant Hodgkin's disease,
      mixed cellularity, and nodular sclerosis type) using digoxigenin-labelled
      oligonucleotide probes for kappa and lambda light chains by in situ
      hybridization. In nearly half of the cases of nodular lymphocyte predominant
      Hodgkin's disease and in one case of mixed cellularity type, mRNA for only one
      light chain could be clearly demonstrated in the lymphocytic and histiocytic
      cells, Hodgkin, and Reed-Sternberg cells. These results support the idea that at
      least some cases of Hodgkin's disease are B-cell neoplasms.

PMID- 8283351
TI  - Glomerular dimensions in children under 16 years of age.
AB  - Glomerular area, perimeter, and mean maximum glomerular diameter were assessed in
      post-mortem kidney tissue from 114 children who died suddenly in accidents and
      who were considered to have been previously healthy. One hundred glomeruli were
      measured from each case using a computer-based measurement system. Regression
      analysis was used to analyse glomerular size with respect to age, body weight,
      height, and body mass index. The estimated mean glomerular area for newborns was
      7934 microns 2 (SE 314), increasing 8 per cent per year to 18,219 microns 2 at 15
      years of age. The estimated mean maximum glomerular diameter increased from 112
      microns (SE 1.9 microns) for newborns, approximately 3.6 microns per year to
      reach 167 microns at age 15. Glomerular size correlated better with age than with
      height, weight, or body mass index, and glomeruli in the inner cortex were
      significantly larger than those in the middle and outer cortex. Glomerular size
      was significantly greater in female children than in the male children over the
      age range examined.

PMID- 8283352
TI  - Immunocytochemical p53 detection by microwave oven heating of routinely formalin
      fixed paraffin sections.

PMID- 8283353
TI  - Microwave oven heating for antigen unmasking in routinely processed tissue
      sections.

PMID- 8283354
TI  - E-cadherin: a biological marker of tumour differentiation.

PMID- 8283355
TI  - Neurogenic bladder dysfunction in children: review of pathophysiology and current
      management.

PMID- 8283356
TI  - Effect of heredity on hemoglobin concentration.
AB  - We studied 5-year-old children and their patients in 80 families and observed an
      association between the hemoglobin concentrations of the children and their
      parents before and after iron medication. We speculate that inheritance may exert
      a significant influence; iron deficiency did not explain the finding.

PMID- 8283357
TI  - Infantile spasms as the initial symptom of biotinidase deficiency.
AB  - Two patients with biotinidase deficiency had diagnoses of infantile spasms made
      at 1 month of age. Biotinidase deficiency may be seen early in the neonatal
      period without the characteristic findings such as alopecia and seborrheic
      dermatitis. This diagnosis should be considered in patients with infantile
      spasms.

PMID- 8283358
TI  - Cytokine elevations in critically ill infants with sepsis and necrotizing
      enterocolitis.
AB  - We hypothesized that plasma levels of cytokines such as interleukin-6 and tumor
      necrosis factor (TNF) are elevated in critically ill infants with sepsis and
      necrotizing enterocolitis (NEC) and that the magnitude of their elevation is
      correlated with mortality rate. We measured plasma levels of interleukin-6 and
      TNF in 62 newborn infants with suspected sepsis or NEC. Eighteen infants had
      bacterial sepsis, 9 had bacterial sepsis plus NEC, and 15 had NEC but negative
      culture results. Twenty comparably ill infants with negative results on culture
      of systemic specimens served as study control subjects. Interleukin-6 levels were
      five- to tenfold higher in infants with bacterial sepsis plus NEC at the onset of
      disease than in infants with bacterial sepsis alone, in infants with NEC but
      negative culture results, and in control infants (p < 0.01). These differences
      persisted throughout the 48-hour study period. Interleukin-6 levels were also
      significantly higher in nonsurvivors than in survivors (p < 0.001). In contrast,
      plasma TNF values were not consistently increased in any of the groups. We
      conclude that plasma interleukin-6 is a more reliable indicator of bacterial
      sepsis and NEC than plasma TNF and may identify infants who might benefit from
      immunotherapeutic strategies.

PMID- 8283359
TI  - Effect of dexamethasone on protein metabolism in infants with bronchopulmonary
      dysplasia.
AB  - Corticosteroids result in protein wasting in human adults and rats. To determine
      to what extent this therapy affects protein metabolism in preterm infants, we
      studied 10 very low birth weight infants before a gradually tapered dexamethasone
      regimen was started and at day 4 of treatment (dexamethasone dosage 0.35 +/- 0.09
      mg.kg-1.day-1), and seven infants at day 19 of treatment (dexamethasone dosage,
      0.10 +/- 0.01 mg.kg-1.day-1). Protein breakdown and turnover rates were increased
      at day 4 of treatment but not any more at day 19 of treatment. Protein synthesis
      rate was not significantly affected during dexamethasone therapy. Weight gain was
      severely diminished during the first week of treatment but not during the next 2
      weeks. We conclude that nitrogen balance during high dosages of dexamethasone is
      significantly lower because of an increase in proteolysis and not because of a
      suppression of synthesis.

PMID- 8283360
TI  - Survival and follow-up of infants born at 23 to 26 weeks of gestational age:
      effects of surfactant therapy.
AB  - Little information is available regarding the effect of surfactant on outcome for
      infants born at or before 26 weeks of gestation. We addressed this issue by
      reviewing records of 310 infants born at gestational ages of 23 through 26 weeks
      who were admitted to our nursery from 1986, when surfactant was introduced,
      through 1990. Surfactant was administered to 154 infants (5 during a single-dose
      prevention study, 25 during a multiple-dose prevention study, 124 while receiving
      a Food and Drug Administration treatment investigational new drug); 156 infants
      were not treated with surfactant. Seventy-three percent of the treated infants
      survived, compared with 55% of the nontreated infants. Increased survival
      occurred at all gestational ages between 23 and 26 weeks but were greatest in
      infants born at 23 and 24 weeks. At follow-up, no differences in neurologic
      outcome were detected between surfactant-treated and nontreated infants. We
      conclude that surfactant use in extremely premature infants improves survival
      rates without increasing the proportion of impaired survivors.

PMID- 8283362
TI  - Erythropoietin levels during theophylline treatment in premature infants.
AB  - Mean erythropoietin levels were somewhat higher in premature infants receiving
      theophylline than in untreated infants with a comparable degree of anemia. These
      results differ from those in adults and may reflect the oxygenation of the
      theophylline-treated patients or the developmental regulation of erythropoietin
      production in response to adenosine receptor antagonists.

PMID- 8283361
TI  - Misalignment of pulmonary veins with alveolar capillary dysplasia: affected
      siblings and variable phenotypic expression.
AB  - Misalignment of pulmonary veins with alveolar capillary dysplasia is recognized
      as a rare cause of persistent pulmonary hypertension of the neonate. Until now,
      misalignment of pulmonary veins was thought to be a random occurrence, but its
      appearance in siblings at our institution suggests that there may be a familial
      predisposition. There have been reports of variable expression and variable
      severity in this disease; our report describes this variability in family
      members.

PMID- 8283363
TI  - Oral versus nebulized albuterol in the management of bronchiolitis in Egypt.
AB  - The efficacy of albuterol in the management of infants with first-time wheezing
      is controversial. This double-blind, placebo-controlled trial involved 128
      Egyptian infants with first-time wheezing (mean age 5.9 months) who were randomly
      separated into four equivalent therapy groups: nebulized albuterol, nebulized
      saline solution, orally administered albuterol, and orally administered placebo.
      The nebulized therapy groups received two treatments 30 minutes apart; the oral
      therapy groups received one treatment. In addition, 41 infants with recurrent
      wheezing comprised an open-label control group who received two albuterol
      nebulizations. Chest radiographs, leukocyte counts, blood culture specimens, and
      nasal aspirate for viral antigen detection were obtained to confirm the clinical
      diagnosis of viral bronchiolitis. Respiratory and heart rates, clinical score,
      and oxygen saturation were recorded at baseline and 30 and 60 minutes after
      treatment. There was no difference among the four randomized groups in any of the
      outcomes except for an increase in heart rate of 10 beats/min in the nebulized
      albuterol group compared with a decrease in heart rate of 8 beats/min in the oral
      placebo group. No differences in the need for additional treatment were observed.
      Nebulized albuterol significantly improved the clinical score and reduced the
      respiratory rate of those with recurrent wheezing relative to those in the
      randomized groups. We conclude that nebulized albuterol is effective in the
      treatment of infants with recurrent wheezing, but there was no demonstrable
      efficacy of orally administered or nebulized albuterol in relieving the
      respiratory distress of infants with bronchiolitis in Egypt.

PMID- 8283364
TI  - Use of adenosine for diagnosis and treatment of tachyarrhythmias in pediatric
      patients.
AB  - This report reviews our experience with the use of adenosine for diagnosis and
      treatment of narrow QRS complex tachyarrhythmias in children. All
      electrocardiograms obtained since the introduction of adenosine for clinical use
      at one pediatric tertiary care institution during an 18-month period were
      reviewed, and those patients receiving adenosine were included for study. Of the
      24 patients who received adenosine, the median age was 4 years; four neonates
      were included. Adenosine produced atrioventricular block in 21 (88%) of 24
      patients. It terminated the tachyarrhythmia in 11 patients and produced
      atrioventricular block but did not terminate the tachyarrhythmia in 10 patients.
      The mechanism of the arrhythmia was known in three patients before adenosine
      administration. Adenosine was useful in establishing the mechanism of the
      tachyarrhythmia in 17 of the remaining 18 patients but was not useful in one
      patient, in whom the arrhythmia was successfully terminated because a good
      quality electrocardiogram was not obtained during adenosine administration.
      Therefore the mechanism of the supraventricular tachycardia was ultimately
      determined for all patients in whom adenosine successfully produced
      atrioventricular block and had acceptable electrocardiographic tracings. Side
      effects were limited and transient. We conclude that adenosine was a safe and
      effective agent for the pharmacologic treatment of narrow QRS complex
      tachyarrhythmias in our patients, including those less than 1 year of age. If
      proper electrocardiographic recordings are performed during adenosine
      administration, it is also helpful in establishing the cause of the
      tachyarrhythmia.

PMID- 8283365
TI  - Evaluation of granulocyte-macrophage colony-stimulating factor for treatment of
      pancytopenia in children with fanconi anemia.
AB  - Fanconi anemia is a congenital syndrome characterized by multiple specific
      physical anomalies, progressive marrow failure, and a predisposition to acute
      leukemia. We studied the toxicity and efficacy of daily subcutaneous
      administration of recombinant human granulocyte-macrophage colony-stimulating
      factor (GM-CSF) in patients with Fanconi anemia and pancytopenia. The toxicity of
      GM-CSF at the doses and schedule used was minimal. Six of seven patients entered
      had an increase in the neutrophil count of 7- to 25-fold, which was maintained
      during the course of study. Despite increases in the reticulocyte count,
      increases in hemoglobin concentration were rare. No improvement in platelet count
      was evident in any patient. No patient has evidence of leukemia after up to 19
      months of continuous GM-CSF exposure, and all five surviving patients remain
      responsive to treatment. Although the optimal dose, schedule, and choice of
      cytokine for patients with marrow failure and Fanconi anemia are not established
      by this preliminary study, the data indicate that (1) GM-CSF may be able to
      palliate at least the neutropenia and potentially the neutropenic complications
      of the disease, (2) this effect can be sustained for more than 1 year, and (3)
      rapid evolution of acute leukemia is unlikely to be a frequent outcome of such
      treatment. The clinical impact of GM-CSF or other cytokines in patients with
      Fanconi anemia and pancytopenia remains to be established by further studies.

PMID- 8283366
TI  - John F. Enders.

PMID- 8283367
TI  - Growth hormone treatment in Down syndrome.

PMID- 8283368
TI  - Profound carnitine palmitoyltransferase II deficiency.

PMID- 8283369
TI  - Apnea in infantile botulism.

PMID- 8283370
TI  - Pain relief during sickle cell crisis.

PMID- 8283371
TI  - Cortical scintigraphy in the evaluation of renal parenchymal changes in children
      with pyelonephritis.
AB  - We designed a prospective study to evaluate the ability of dimercaptosuccinic
      acid cortical scintigraphy and ultrasonography to detect renal parenchymal
      lesions in children with pyelonephritis. One hundred eleven patients 1 week to 16
      years of age (median 5.5 months) with a urine culture positive for pathogens were
      included in the study; cortical scintigraphy and ultrasonography were repeated in
      25 children after a mean follow-up of 10.5 months. Cortical scintigraphy showed
      renal changes in 74 children (67%), and ultrasonography showed renal changes in
      39 (35%) (p < 0.001); results of the two examinations were discordant in 49
      patients (kappa = 0.19). Children more than 1 year of age had a higher incidence
      of renal lesions than did younger children (85% vs 66%; p = 0.04). The presence
      of inflammatory signs (erythrocyte sedimentation rate or C-reactive protein) had
      an 89% sensitivity and a 25% specificity in identifying renal lesions. Among
      children with renal changes, vesicoureteric reflux was present in 39%. At follow
      up examination, 16 children (64%) had scars. Thus we found a high incidence of
      renal involvement in children with pyelonephritis. We found that cortical
      scintigraphy is more sensitive than ultrasonography in detecting renal changes,
      and we believe that it should be added to the initial examination of children
      with suspected pyelonephritis.

PMID- 8283372
TI  - Epidemic Escherichia coli O157:H7 gastroenteritis and hemolytic-uremic syndrome
      in a Canadian inuit community: intestinal illness in family members as a risk
      factor.
AB  - OBJECTIVE: To evaluate risk factors for childhood hemolytic-uremic syndrome (HUS)
      and gastroenteritis during an epidemic of Escherichia coli O157:H7 infection.
      DESIGN: Case-control study. SETTING: Remote Inuit community of Arviat in northern
      Canada. PARTICIPANTS: Of the 565 Arviat residents less than 15 years of age, 19
      had HUS and 65 more had E. coli O157:H7 gastroenteritis. The 19 children with HUS
      were compared with 19 age- and gender-matched children with uncomplicated E. coli
      O157:H7 gastroenteritis, and both HUS and gastroenteritis patients were compared
      with 19 healthy control subjects. INTERVENTIONS: Questionnaire administered face
      to-face to parents of participants in the home. MAIN OUTCOME MEASURES: Rates of
      exposure to foods, travel, sources of water, and gastrointestinal illness in
      family members. RESULTS: Patients with HUS and those with uncomplicated E. coli
      O157:H7 gastroenteritis differed only on measures of clinical severity. In the 7
      days before the onset of gastrointestinal symptoms, children with HUS and those
      with uncomplicated gastroenteritis were more likely to have been exposed to a
      family member with diarrhea than were the healthy control subjects (odds ratio =
      9 for HUS vs healthy control subjects; 95% confidence interval 2 to 43; p <
      0.01). Undercooked ground meat and foods traditionally consumed by the Inuit were
      not implicated as risk factors in E. coli O157:H7 infection. CONCLUSIONS: These
      findings emphasize the potential for extensive intrafamilial transmission of
      verotoxin-producing E. coli once infection is introduced into certain
      communities.

PMID- 8283373
TI  - Infantile systemic lupus erythematosus with onset simulating congenital nephrotic
      syndrome.
AB  - Two white female infants were seen with congenital nephrotic syndrome at age 6
      weeks and 3 months, respectively. Both had hypocomplementemia, elevated
      antinuclear antibody and anti-double-stranded DNA titers, and diffuse
      proliferative glomerulonephritis with positive immunofluorescence in their
      initial renal biopsy samples. Although uncommon, infantile systemic lupus
      erythematosus should be considered in the evaluation of congenital nephrotic
      syndrome.

PMID- 8283374
TI  - Growth and intakes of energy and zinc in infants fed human milk.
AB  - The objectives of this study were to examine the growth pattern of healthy
      infants who were fed human milk exclusively for > or = 5 months and its
      relationship to intakes of milk, energy, and zinc. Monthly anthropometric
      measurements were obtained on 71 infants through 7 months of age and on 43
      through 9 months. Milk zinc concentrations were determined and milk intake was
      measured by 3-day test weighing. Mean (+/- SD) calculated energy intake from
      human milk was 106 +/- 20, 79 +/- 11, 70 +/- 10, and 57 +/- 12 kcal/kg per day at
      2 weeks and 3, 5, and 7 months of age, respectively; intake from milk plus solids
      was 70 +/- 13 kcal/kg at 7 months. Zinc intakes from human milk were 2.3 +/-
      0.68, 1.0 +/- 0.43, 0.81 +/- 0.42, and 0.52 +/- 0.31 mg/day at these points. The
      maximum mean weight-for-age percentile for both sexes was 62 at 2 months; the
      mean percentile declined to 33 by 7 months and to 25 by 9 months of age. Mean
      length-for-age percentile declined from 43 at 2 weeks of age to 28 and 26 by 7
      and 9 months of age, respectively. Energy intake at 2 weeks of age was positively
      associated with the weight increment from 2 weeks to 7 months of age (p = 0.003)
      and with a change in weight-for-age z scores from 2 weeks to 3 months of age (p =
      0.028). Mean energy intakes of healthy breast-fed infants are lower through the
      first 7 months of life than current recommendations. Zinc intakes of breast-fed
      infants are likely to be adequate, on average, through 5 months of breast-feeding
      but subsequently are marginal without the introduction of weaning foods. Revision
      of standards for growth based on observations in breast-fed infants may be
      appropriate, but the possibility of growth-limiting nutrient deficiencies should
      also be investigated.

PMID- 8283375
TI  - Sclerosing cholangitis in children.
AB  - We report on 56 children with sclerosing cholangitis (SC) seen between 1972 and
      1992. The first symptoms occurred at a mean age of 3.7 years; 15 infants had
      neonatal cholestatic jaundice. At diagnosis, cholestatic jaundice was present in
      25 children, hepatomegaly in 54, splenomegaly in 41, and ascites in 12. Serum
      alkaline phosphatase activity was increased in 49 patients and gamma
      glutamyltransferase activity in all patients tested. Most often the
      histopathologic findings were extensive portal fibrosis and neoductular
      proliferation. Cholangiography showed abnormal intrahepatic bile ducts in all
      children and abnormal extrahepatic bile ducts in 35 (63%). The children were
      separated into three groups: (1) those with SC of neonatal onset (27%); (2) those
      with SC of postneonatal onset associated with another disease (55%)-
      histiocytosis X in 14 children, immunodeficiency syndromes in 8, chronic
      inflammatory bowel disease or autoimmune hepatitis in 8, and congenital psoriasis
      in 1; and (3) those with SC of postneonatal onset without an associated disease
      (18%). Biliary cirrhosis was present in all but three children after 6 months to
      19.3 years of follow-up. Eleven children died of portal hypertension or liver
      failure, and six died of a complication related to the associated disease.
      Fifteen children had liver transplantation; 11 of these are alive 6 months to 6
      1/2 years later without recurrence of SC. The overall estimated median survival
      time of children with SC was 10 years from clinical onset. These results indicate
      that SC should be suspected in all children with a chronic cholestatic disease
      and increased serum gamma-glutamyl transferase activity, especially when diseases
      known to be associated with SC are present. The prognosis is poor, but liver
      transplantation should be considered except in those with severe immunodeficiency
      syndromes.

PMID- 8283376
TI  - Lymphocytic gastritis: a positive relationship with celiac disease.
AB  - Lymphocytic gastritis is characterized by lymphocytic infiltration of the surface
      and pit epithelium. Its cause has not been established, but an association with
      Helicobacter pylori infection or celiac disease has been suggested. We evaluated
      the histologic features of both gastric and duodenal biopsy specimens from 245
      consecutive children and adolescents, and found chronic gastritis in 60 children
      and celiac disease in 25. Chronic gastritis was associated with H. pylori
      infection in 36 children and with celiac disease in 15. Lymphocytic gastritis was
      found in nine children with celiac disease. Children with lymphocytic gastritis
      had a mean of 40.64 lymphocytes per 100 epithelial cells, compared with a mean of
      3.92 lymphocytes per 100 epithelial cells in children with H. pylori-associated
      gastritis and 5.15 lymphocytes in normal control subjects. Immunohistochemical
      studies showed that the intraepithelial lymphocytes in lymphocytic gastritis were
      T cells. No child with lymphocytic gastritis had serologic evidence of past H.
      pylori infection. We conclude that lymphocytic gastritis in children is
      associated with celiac disease. Dyspeptic symptoms are frequent; the endoscopic
      appearance is not characteristic.

PMID- 8283377
TI  - Mitochondrial DNA rearrangements with onset as chronic diarrhea with villous
      atrophy.
AB  - We report two unrelated children with onset of chronic diarrhea and villous
      atrophy in the first years of life. Elevated plasma lactate concentrations and
      lactate/pyruvate and ketone body molar ratios suggested a genetic defect of
      oxidative phosphorylation. Analysis of the mitochondrial respiratory chain showed
      a complex III deficiency in muscle of both patients. Southern blot analysis
      provided evidence of heteroplasmic mitochondrial DNA rearrangements that involve
      deletion and deletion-duplication. Directly repeated sequences (10 and 11 base
      pairs, respectively) were present in the wild type of mitochondrial genome at the
      boundaries of the deletion. Neither parent of either patient had rearranged
      molecules in their circulating lymphocytes. It appears that a mitochondrial
      disorder can have chronic diarrhea and villous atrophy as the initial clinical
      feature. On the basis of these observations, we suggest that genetic defects of
      mitochondrial energy supply be considered in elucidating the origin of
      unexplained chronic diarrheas, especially when other, unrelated symptoms occur in
      the course of the disease.

PMID- 8283378
TI  - Mondini dysplasia and congenital cytomegalovirus infection.
AB  - We report a case of bilateral temporal bone anomalies in a child with symptomatic
      congenital cytomegalovirus infection and severe, bilateral sensorineural hearing
      loss identified at 3 months of age. High-resolution temporal bone computed
      tomography (HRCT) revealed bilateral findings of a short, malformed cochlea
      lacking an interscalar septum, a short and wide internal auditory canal, and an
      enlarged vestibular aqueduct, features diagnostic of bilateral Mondini dysplasia.
      To determine the importance of this observation, we completed HRCT in five
      additional children between 7 months and 9 years of age who had evidence of
      symptomatic congenital cytomegalovirus infection. One child with profound
      sensorineural hearing loss had severe bilateral temporal bone dysplasia with a
      small cochlea lacking an interscalar septum, an abnormal vestibule, and a large
      cochlear aqueduct. Of the remaining four children, hearing thresholds ranged from
      normal to profoundly decreased, but their HRCT scans were normal to visual
      inspection. When inner ear dimensions of these temporal bones were compared with
      norms established by Pappas and coworkers, however, seven of the eight ears had
      short cochleas and narrow lateral semicircular canals, and three ears had short
      or narrow vestibules. These results indicate that congenital cytomegalovirus
      infection may cause anomalies or growth disturbances of the temporal bone.

PMID- 8283379
TI  - A new syndrome with ethylmalonic aciduria and normal fatty acid oxidation in
      fibroblasts.
AB  - We describe four Italian male infants with a novel clinical phenotype
      characterized by orthostatic acrocyanosis, relapsing petechiae, chronic diarrhea,
      progressive pyramidal signs, mental retardation, and brain magnetic resonance
      imaging abnormalities. The first symptoms appeared after the termination of
      breast-feeding and introduction of formula feeding. Marked persistent 2
      ethylmalonic aciduria was associated with abnormal excretion of C4-C5(n-butyryl-,
      isobutyryl-, isovaleryl-, and 2-methylbutyryl-)acylglycines and acylcarnitines
      and with intermittent lactic acidosis. Short- and branched-chain plasma
      acylcarnitine levels were also elevated. 2-Ethylmalonic aciduria is generally
      regarded as being indicative of a defect in fatty acid oxidation. Extensive
      studies of cultured fibroblasts failed to reveal such a defect. The observation
      of intermittent urinary excretion of 2-ethylhydracrylic acid pointed to
      involvement of the isoleucine R pathway in ethylmalonate biosynthesis. This
      hypothesis was tentatively corroborated by the biochemical responses to an oral
      isoleucine challenge in two patients. However, fibroblast studies showed normal
      oxidation rates of (14C)isoleucine (ul), indicating that this is not a defect of
      isoleucine oxidation expressed in skin fibroblasts. In one of two patients
      tested, cytochrome c oxidase activity was partially reduced (45%) in cultured
      fibroblasts. This unique clinical and biochemical phenotype identifies a new
      metabolic encephalopathy of yet undetermined cause.

PMID- 8283380
TI  - Evolving role of nuclear medicine for the diagnosis and management of urinary
      tract infection.

PMID- 8283381
TI  - Kegel exercises and childhood incontinence: a new role for an old treatment.
AB  - Kegel exercises were used to treat urinary incontinence in 79 children. An
      average of less than 2 hours of professional time was required. Incontinence was
      eliminated in 60% of the patients; children who had both day and night wetting
      tended to show simultaneous improvements in both problems. Research is needed to
      test the hypothesis that Kegel exercises eliminate involuntary contractions of
      the detrusor muscle.

PMID- 8283382
TI  - Comparison of oxygenation measurements in pediatric patients during sickle cell
      crises.
AB  - Measurements of the saturation of arterial blood with oxygen (SaO2) were compared
      in 24 children during sickle cell crises. Simultaneous pulse oximetry (Nellcor N
      100 pulse oximeter) and arterial blood analysis showed that SaO2 measured by
      pulse oximetry overestimated cooximeter-measured SaO2 (mean bias, 6.9%; p <
      0.001). The blood gas machine-calculated SaO2 also overestimated cooximeter
      measured SaO2 (p < 0.001). The bias increased with increasing age (p = 0.002) and
      carboxyhemoglobin level (p = 0.005) but was not related to methemoglobin, total
      hemoglobin, percentage of hemoglobin S, or percentage of hemoglobin F.

PMID- 8283383
TI  - Partial splenic embolization in children with hypersplenism.
AB  - As an alternative to surgical splenectomy, partial splenic embolization was
      performed in seven children for hypersplenism manifested by splenomegaly,
      thrombocytopenia, leukopenia, and erythrocyte hemolysis. Within a few days,
      platelet and leukocyte counts rose significantly in all patients and were
      maintained in six of seven patients during a follow-up period of 9 to 69 months.
      Spleen size and abdominal distention also decreased significantly in all
      children. There were no infectious complications.

PMID- 8283384
TI  - Antigonadal effects of two novel melatonin analogues in adult Djungarian
      hamsters.
AB  - This study examined the effects of two novel melatonin analogues in adult
      Djungarian hamsters housed under long photoperiod (LD 16:8). Daily injection (10
      micrograms, s.c.) of either melatonin, 5-methoxy N-butanoyltryptamine (bMT), or 5
      methyl N-butanoyltryptamine (5-MebT) 3 hr before lights off for 8 weeks led to a
      significant decrease in paired testis weight compared to vehicle-injected
      controls. The reduction in testis weight was of similar magnitude with melatonin
      and bMT, but 5-MebT was not as effective. The affinity of the analogues was
      determined in competition experiments using chicken brain membranes and 2
      [125I]iodomelatonin (2-[125I]aMT). Replacing the N-acetyl side-chain of melatonin
      with an N-butanoyl group increased affinity for the chicken brain 2-[125I]aMT
      binding site, but exchanging the 5-methoxy group of melatonin for a 5-methyl
      group reduced affinity. These studies show that these analogues not only inhibit
      2-[125I]aMT binding in vitro but also mimic melatonin's antigonadal activity in
      vivo.

PMID- 8283385
TI  - Characterization and localization of delta opioid binding sites in the bovine
      pineal gland.
AB  - Opioid binding sites in the bovine pineal were characterized using the highly
      selective delta opioid agonist 3H-[D-Pen2,pCl-Phe4,D-Pen5] enkephalin
      (DPDP(C1)E). Pineal membranes possess a single class of high affinity binding
      sites for this delta ligand (Kd = 0.26 nM; Bmax = 250 fmol/mg protein). The
      specific opioid antagonist naloxone dose dependently inhibited 3H-DPDP(C1)E
      binding, confirming that this ligand is indeed binding to opioid receptors. The
      delta selective ligands deltorphin and [D-Pen2,5]enkephalin (DPDPE) were much
      more potent than the mu selective compounds dermorphin and [D-Ala2,MePhe4,Gly5-
      ol]enkephalin (DAMGO) in inhibiting 3H-DPDP(C1)E binding. These results
      demonstrate that in bovine pineal membranes, DPDP(C1)E binds to delta opioid
      sites. Autoradiographic studies showed a uniform distribution of 3H-DPDP(C1)E
      binding over the bovine pineal in the sections we analyzed. This distribution
      suggests that delta opioid binding sites are associated with pinealocytes which
      account for the majority of cell types in the pineal. However, it is not possible
      to rule out that these receptors may also be associated with other cell types
      which are present in the bovine pineal. The density and widespread distribution
      of delta opioid receptors supports the hypothesis that endogenous opioid peptides
      directly modulate pineal function.

PMID- 8283386
TI  - Distribution of melatonin in mammalian tissues: the relative importance of
      nuclear versus cytosolic localization.
AB  - Besides its presence in the pineal gland, melatonin has been found in a variety
      of other tissues as well. The indoleamine also has been identified in
      invertebrates including an unicellular organism where it exhibits a diurnal
      rhythm. Although melatonin is mainly known for its effects on seasonal
      reproduction and endocrine physiology, there is evidence showing that this
      ubiquitously acting hormone is also a potent free radical scavenger, thereby
      providing protection from oxidative attack to DNA and other biomolecules. Through
      the years, melatonin was thought to be exclusively cytosolic. However, careful
      examination of some of these pioneering reports revealed a nuclear localization
      of melatonin in different tissues including the retina and Harderian glands.
      Using a very sensitive immunocytochemical method, we have also found that
      melatonin is located in the nucleus of many cells where it may bind to nuclear
      components. The use of cell fractionation studies followed by radioimmunoassay
      confirmed these results. The administration of exogenous melatonin resulted in a
      marked increase in the nuclear melatonin content without a concomitant change in
      the cytosolic fraction. In addition to its ability to scavenge free radicals, its
      location in the nucleus suggests possible genomic actions.

PMID- 8283387
TI  - Effects of nightbreak, T-cycle, and resonance lighting schedules on the pineal
      melatonin rhythm of the lizard Anolis carolinensis: correlations with the
      reproductive response.
AB  - Experiments were conducted to determine if a correlation exists between any
      aspect of the pineal melatonin rhythm (such as its duration or phase) in the
      lizard Anolis carolinensis and the reproductive response to photoperiod. The
      rhythm of pineal melatonin content was determined in anoles exposed to nightbreak
      lighting protocols (10L:5D:1L:8D, 10L:10D:1L:3D), resonance lighting cycles (LD
      11:13, LD 11:25), and T-cycle lighting protocols (LD 11:7, LD 11:9, LD 11:13, LD
      11:15, LD 11:19) and compared with the testicular response to these lighting
      protocols as determined previously [Underwood and Hyde, (1990) J. Comp. Physiol.
      (A) 167:231-243]. Different T-cycles and nightbreak cycles elicited changes in
      both the duration of the melatonin peak and the phase of the melatonin peak
      relative to these light cycles. The response to the resonance cycle (LD 11:25)
      was complex, probably due to the overlapping patterns of two groups whose pineal
      melatonin rhythms were entrained approximately 12 hr out of phase with each
      other. No correlation was observed between the duration, or the amplitude, of the
      nocturnal melatonin peaks seen on the various light cycles and the reproductive
      response to these cycles. A correlation was observed between the phase of the
      pineal melatonin rhythm and the reproductive response. Light cycles were
      inductive (stimulated testicular growth) when the entrained melatonin rhythm
      peaked near the light-to-dark or the dark-to-light transition, but they were not
      inductive when the melatonin rhythm peaked during the middle third of the night.
      These results suggest that if melatonin is involved in the transduction of
      photoperiodic information in Anolis, neither the duration nor amplitude of the
      nocturnal melatonin pulse is involved in the measurement of day length. Instead,
      the phase-relationship of the melatonin rhythm to the rest of the circadian
      system may determine photoperiodic responsiveness.

PMID- 8283388
TI  - Commonalities in vasoactive intestinal peptide and peptide N-terminal histidine C
      terminal isoleucine stimulation of N-acetyltransferase activity in the rat
      pineal.
AB  - Exposure of adult rat pineal glands in organ culture to the polypeptides
      vasoactive intestinal polypeptide (VIP), and peptide N-terminal histidine C
      terminal isoleucine (PHI) increases pineal serotonin N-acetyltransferase (NAT)
      activity and melatonin synthesis. The following research results are taken to
      indicate that VIP and PHI share common components of the NAT induction system:
      (1) The effects of the two peptides are additive at concentrations of 10 nM VIP
      and 100 nM PHI but not at higher peptide concentrations. (2) Pineals from
      newborns also respond to PHI with a dose dependent increase in NAT activity. NAT
      responses are additive at the same concentrations as seen with the adult pineals.
      (3) Light exposure affects the sensitivity of pineals to VIP and PHI stimulation
      in a similar manner; pineals taken after 3 hr of light are much less sensitive to
      PHI or VIP than those taken after 13 hr of light. (4) Pineals exposed for 48 hr
      to either PHI or VIP have a reduced NAT response to either agonist, which is
      reversible by culture in agonist-free media. (5) Neither VIP nor PHI stimulation
      of NAT activity is affected by concentrations of the VIP antagonists (N-Ac-Tyr1,D
      Phe2)-GRF(1-29)-NH2 (NAcTDGRF), L-8-K, VIP-Neurotensin Hybrid (VIPNET), or (4Cl-D
      Phe6, Leu17)-VIP (4C1PLVIP), which affect VIP binding or function in other
      tissues.

PMID- 8283389
TI  - New sensitive serum melatonin radioimmunoassay employing the Kennaway G280
      antibody: Syrian hamster morning adrenergic response.
AB  - A new procedure with the G280 antibody of Kennaway provides an assay for
      circulating melatonin (aMT) with a sample volume (200 microliters), an analytic
      (0.33 pg/ml) and functional (0.62-0.80 pg/ml) detectability, a 50% displacement
      dose (6.4 pg/ml), a Kd (0.657 pM), and measured circulating daytime levels lower
      than reported for previous procedures, and 100% assay recovery. The normal
      daytime range in adult human and Syrian hamster serum was 0.4-4 pg/ml. The
      pattern of fall of the nocturnal surge of Syrian hamster serum aMT near the time
      of lights-on was unaltered by extended darkness. Isoproterenol (ISO) injection 1
      hr after lights-on, when aMT had reached daytime levels, raised serum and pineal
      aMT dramatically 2 hr postinjection. The same dose of ISO injected 4 hr into
      light produced only a small detectable increase. Novel extension of nocturnal
      darkness did not affect the responses to ISO. Thus, when they are allowed to
      occur at the usual time on a 10-hr dark schedule, both the fall from the
      nocturnal aMT surge and the subsequent loss of pineal beta-adrenergic
      responsiveness in this species occur endogenously (probably entrained) rather
      than from gating by acute effects of morning light. Changes in daytime serum aMT
      consistent with concomitant changes in the pineal can be measured with a
      sufficiently sensitive radioimmunoassay.

PMID- 8283390
TI  - Repair of distal tendo Achillis rupture with the use of the Mitek Anchor System.
AB  - Surgical repair of an acute, distal, tendo Achillis rupture in a 59-year-old
      diabetic male is described in which the Mitek Anchor System was used. The injury
      described is a distal tear of the insertion of the tendon into the calcaneus
      without avulsion fracture of the calcaneus. Sixteen months of postoperative
      follow-up care, including casting for equinus deformity, progressive
      weightbearing, range of motion exercises, and physical therapy, have been free of
      complications. The authors include a brief overview of historical and current
      reparative techniques for comparison. The authors conclude that the use of the
      Mitek Anchor System affords the surgeon a simple and effective method for the
      repair of acute, distal, tendo Achillis rupture when other methods cannot be used
      because of the location of the rupture.

PMID- 8283391
TI  - Comparison of the effectiveness of nail dust extractors.
AB  - Electrical debridement of nails results in hazardous airborne particles. This
      study compares the effectiveness of several nail dust extractors in reducing the
      amount of this debris. All extractors were more effective than the control, with
      a minimum of 24.6% effectiveness to a maximum of 91.6%.

PMID- 8283392
TI  - Pressure distribution beneath the human foot.
AB  - A descriptive study was undertaken to establish the 95 percentile limits
      (proposed normal reference range) for pressure beneath the hallux, metatarsal
      heads, and heel in a group of healthy adult subjects. A new force plate device
      capable of accurately measuring discrete areas of pressure beneath the human foot
      with high temporal and spatial resolution was used. The system is capable of
      accurately measuring plantar foot pressure during dynamic and static foot
      function. The results of this research are in close agreement with other
      published studies of plantar foot pressure measurement with comparable systems.

PMID- 8283393
TI  - Solitary periungual angiofibroma. An unusual case report.
AB  - Solitary periungual angiofibromas can often be challenging in the diagnosis and
      treatment of such common lesions. Because of the various histologic presentations
      of fibrous skin tumor, a complete differential diagnosis would include
      hemangioma, seborrheic keratosis, fibroma, and digital fibrokeratoma. Treatment
      by total sharp excision can often be accomplished, depending on the morphological
      appearance of the lesion. An incisional biopsy of a more expansile lesion may be
      warranted.

PMID- 8283394
TI  - Hematogenous osteomyelitis of the calcaneus.
AB  - A case report of hematogenous calcaneal osteomyelitis has been presented along
      with a brief review. Hematogenous osteomyelitis of the foot is an uncommon but
      potentially devastating disease that can result in severe long-term sequelae. An
      index of suspicion in cases such as these can help the physician prevent
      unnecessary delay in treatment. In pediatric hematogenous osteomyelitis, oral
      antibiotics can often be sufficient for long-term therapy, provided sufficient
      surgical decompression is performed.

PMID- 8283395
TI  - Assessment of peripheral vascular disease in diabetes. Report and recommendations
      of an International Workshop sponsored by the American Heart Association and the
      American Diabetes Association 18-20 September 1992, New Orleans, Louisiana.

PMID- 8283396
TI  - Clinical sign consistent with the hallucal interphalangeal sesamoid.

PMID- 8283397
TI  - Functional hallux limitus.

PMID- 8283398
TI  - Congenital deformities of the lower extremities.

PMID- 8283399
TI  - Oncogenes, tumor suppressors and viruses in oral squamous carcinoma.
AB  - The pathogenesis of oral squamous cell carcinoma involves recognised carcinogens
      in tobacco and/or alcohol but other factors, including viruses, may also have a
      role. This paper reviews the gene changes revealed in oral carcinoma, the
      evidence implicating viruses, and mechanisms whereby viruses may affect gene
      function.

PMID- 8283400
TI  - Cytomegalovirus: a virus of increasing relevance to oral medicine and pathology.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus, emerging as an
      opportunistic pathogen in immunocompromised persons, particularly those infected
      with human immunodeficiency viruses (HIV). Clinical syndromes caused by HCMV are
      usually not specifically identifiable without laboratory investigations. However,
      it is now apparent that HCMV may cause oral ulceration in immunocompromised
      persons and it may play a role in other diverse conditions in these and other
      patients.

PMID- 8283401
TI  - Ultrastructural localization of microliths in salivary glands of cat.
AB  - Although microliths occur in normal human salivary glands and may be an
      aetiological factor of sialadenitis, little is known of their natural history. In
      an attempt to remedy this, we investigated a large archival collection of normal
      and experimental feline parotid, submandibular and sublingual salivary glands. In
      submandibular and sublingual glands, microliths were detected ultrastructurally
      in: all types of acinar secretory cells; myoepithelial cells; ductal cells;
      lumina; intercellular spaces; basement membrane; stroma; macrophages;
      multinuclear giant cells; and neutrophils. Microliths were not detected
      ultrastructurally in parotid glands. Microliths appear to form in acinar cells
      during autophagy and in stagnant secretory material in lumina. Microliths appear
      to be removed by secretion in the saliva, discharge from cells laterally and
      basally, and engulfment by macrophages. There appears to be a turnover of
      microliths, which possibly is upset by secretory inactivity with a resulting
      accumulation that leads to localized obstruction and sialadenitis.

PMID- 8283402
TI  - Canalicular adenoma: report of five cases with ultrastructural observations.
AB  - Canalicular adenomas from five patients were examined by light and electron
      microscopy. All patients were over 50 years of age; 4 of the lesions were from
      the upper lip, 4 were cystic, 2 showed capsular invasion and 1 was multifocal.
      Histopathologically there were epithelial duct-like or canalicular structures cut
      at various angles and epithelial islands surrounded by hyalinized and mucinous
      connective tissue that contained little collagen. Ultrastructurally the
      epithelial islands contained many small lumina and connective tissue islands. The
      characteristic epithelial cell was columnar or cuboidal, extended from the lumina
      to the connective tissue, had almost straight lateral cell boundaries with
      desmosomes that predominated near the lumina, and possessed gap junctions and a
      small number of tight junctions. Their main cytoplasmic constituents were
      ribosomes, mitochondria, rough-surfaced endoplasmic reticulum and microfilaments.
      These findings show that canalicular adenomas are truly monomorphic and support
      the concept that they are derived from the cells of excretory ducts.

PMID- 8283403
TI  - Lichen sclerosus et atrophicus involving the oral mucosa: report of two cases.
AB  - Lichen sclerosus et atrophicus (LSA) is a relatively rare dermatosis of unknown
      etiology. The disease is clinically characterized by white, macular lesions on
      the skin, and is usually associated with an atrophic condition affecting the
      vulva and peri-anal skin. Involvement of the oral mucosa with or without
      concurrent genital or skin lesions has been reported only occasionally in the
      literature. In the present paper two new cases of oral LSA are presented, which
      were, in fact, the only manifestation of the disease. Furthermore, the
      epidemiologic, etiologic, clinical and histopathologic aspects of oral LSA are
      discussed.

PMID- 8283405
TI  - [The Department of Radiology at the University of California, San Francisco].

PMID- 8283404
TI  - Non-calcifying Pindborg tumor with Langerhans cells.
AB  - A rare case of calcifying epithelial odontogenic tumor (CEOT) devoid of
      calcification is reported with histochemical, immunohistochemical and electron
      microscopic studies. The tumor occurred intraosseously in the left maxillary
      canine and premolar region of a 58-year-old man. The tumor chiefly consisted of
      scattered small islands of epithelial cells in an abundant fibro-myxoid
      connective tissue stroma. Among the nests, there were many spherical bodies of
      eosinophilic substance for which non-AA amyloid and non-keratin or basal lamina
      like natures were demonstrated histochemically and immunohistochemically. In some
      nests, there were a few, occasionally several, cells positive for S-100 protein.
      Ultrastructurally, Langerhans cells with indented nuclei and Birbeck's granules
      were seen among tumor cells. The prognostic significance of the paucity of
      calcification and the presence of Langerhans cells in CEOT of which this is only
      the second description is discussed.

PMID- 8283406
TI  - [Aortic traumatic lesion. Has tomodensitometry a role?].
AB  - The low positive yield from aortography in patients with suspected traumatic
      aortic rupture has prompted research into CT of the mediastinum as a screening
      investigation which could significantly reduce the number of negative angiograms
      performed. Much of the data published to date suggest a promising role for CT,
      but false negative scans have been reported and the precise false negative rate
      has yet to be determined. We propose an algorithm for the use of CT in suspected
      traumatic rupture but emphasise that continuous monitoring of outcomes and
      further large studies are required before CT can become an established screening
      technique.

PMID- 8283407
TI  - [Role of radiology in the diagnosis of joint chondrocalcinosis. Calcium
      pseudogout].
AB  - Chondrocalcinosis is a really frequent clinicopathologic entity, which is caused
      by the penetration of calcium pyrophosphate dihydrate microcrystals into the
      structures of the joint, including hyaline cartilages and fibrocartilages--hense
      its name--as well as the synovial fluid and membrane. Calcium gout, which
      preferentially appears in the knees, is the most spectacular and characteristic
      symptom of chondrocalcinosis, expressing a crisis of acute microcrystal
      synovitis, of which it has all the usual clinical features, and thus simulating
      uratic gout. The positive diagnosis is based on: a) the radiologic demonstration
      of articular calcifications in the lining cartilages, forming a continuous or
      fragmented opaque border on the subchondral bone, from which it is separated by a
      light space, and/or in the fibrocartilaginous structures (most often the menisci,
      the symphysis pubis, the disk of the inferior radioulnar joint) where they appear
      as small, irregular clusters with blurred or cloudy margins. The knee is the most
      frequent site of calcium impregnation images, both in hyaline cartilages and in
      fibrocartilages. b) the presence of calcium pyrophosphate microcrystals in the
      synovial fluid; their nature is usually demonstrated convincingly enough with a
      conventional light microscope; c) needle biopsy findings of microcrystalline
      clusters embedded in the synovial membrane, that can be easily identified with
      routine staining. In practice, demonstrating radiologic signs, when these are
      characteristic and can be detected in their preferred sites, allows recognizing
      diffuse chondrocalcinosis in satisfactory safety conditions after a calcium gout
      crisis, as well as in the presence of the many atypical or misleading symptomatic
      aspects of this microcystal arthropathy, that will be the subject of a further
      paper.

PMID- 8283408
TI  - [Intrathoracic hydatid cyst. Contribution of tomodensitometry. Apropos of 25
      cases].
AB  - Twenty-five cases of thoracic hydatic disease, studied by CT since 1982, are
      reviewed. Fifteen patients were Maghrebin, 10 were native. The lungs were
      interested 22 times, the mediastinum 3 times and the heart only once.
      Complications of hydatic disease were present 8 times. We compare contribution of
      CT to the other diagnosis criterious. Our results show the accuracy of CT for the
      diagnosis of non complicated cyst and the lack of specificity for complicated
      cysts.

PMID- 8283409
TI  - [Aneurysm in a persistent sciatic artery. Apropos of 2 cases].
AB  - Persistent sciatic is a vascular malformation resulting in the embryo from the
      preferential growth of the ischiatic posterior axis remaining atrophic. We report
      here two cases of unilateral, complete and incompleted, persistent sciatic
      arteries, complicated by buttock aneurysm.

PMID- 8283410
TI  - [Cholesteatoma of the posterior cerebral fossa. 7 cases and review of the
      literature].
AB  - Fifty percent of intracranial epidermoid cysts are located in the cerebral
      posterior fossa. Clinical presenting features are not specific and vary according
      to cyst topography and mass effect on neighbouring structures. In CT, the lesion
      is hypodense as related to the cerebral tissue, but with no specificity. In MRI,
      the typical form shows quasi-pathognomonic morphologic characters with polyedric
      contours, a marble aspect, a reduced mass effect as compared to the tumor volume
      and an evolution signal close to that of cerebrospinal fluid, with no increase
      after contrast agent injection. Some primary cholesteatomas have a different
      radiological aspect. They can be hyperdense in CT and have a spontaneous
      hyperintense signal in T1-weighted MRI sequence. They correspond to complicated
      epidermoid cysts associated with hemorrhages and granulomatous meningeal reaction
      whose constitution is very very close to that of cholesterine granulomas.

PMID- 8283411
TI  - [Brain and spinal cord cavernoma. Value of MRI and review of the literature.
      Apropos of a case].
AB  - MRI has transformed the diagnosis of cavernous hemangioma, a hamartoma that is
      most often located in the central nervous system. The appearance of this lesion
      is fairly characteristic with MRI. This technique has allowed distinguishing
      multiple forms. Encephalic sites are most frequent, with rare medullary sites,
      and double brain and cord locations are exceptional. Many cases of single or
      multiple brain involvement have now been reported. Series of medullary
      involvement are much less frequent and include few cases. Double sites in the
      brain and cord are exceptional. The authors present a case of cavernous
      hemangiomas of the central nervous system with multiple encephalic sites
      associated with a single medullary site confirmed by surgery.

PMID- 8283412
TI  - [Prognostic value of x-ray computed tomography in acute pancreatitis. Value of a
      new classification].
AB  - CT plays an important role in the screening of complications of acute hemorrhagic
      pancreatitis. There are three classifications at present, one based on a
      bioclinical score (Ranson) and the other two consisting of gradual stages of
      severity and resorting to CT imaging (Balthazar and Hill). The authors report
      about a study on 34 cases of acute pancreatitis, including 10 that became
      complicated, to which they applied a new classification including the existence
      of glandular necrosis, the number of extrapancreatic streaks, related to Ranson's
      bioclinical score. This classification makes it possible to classify acute
      pancreatitis into three stages: a mild stage with a favorable outcome, a medium
      stage requiring close surveillance, and stage 3 involving a high (75%) risk of
      severe complications.

PMID- 8283413
TI  - [Criteria of indication of puncture of amebic liver abscesses. 228 patients].
AB  - To clarify the therapeutic role of US-guided in the treatment of amebic liver
      abscess, three different approach to amebic liver abscess were tested in 228
      patients (187 males and 31 females) along 3 years. In a west african endemic area
      (in Abidjan). All cases were correctly diagnosed by clinical and sonographic
      findings, and by the pus after percutaneous or chirurgical drainage. The three
      modes of therapy utilized segregated three distinct group. The first group
      consisted of 80 patients who were treated medically by metromidazole and
      ampicillin administered orally. In them, 33 patients have noncollected abscess
      with a diameter ranged from 2.3 to 12.7 cm (mean 6.6 cm), 23 patients have a
      collected abscess with a diameter less than 10 cm ranged from 4.1 to 9.7 cm (mean
      7.1 cm), 24 patients have a collected abscess with a diameter equal or exceeding
      10 cm ranged from 10 to 22.5 cm (mean 14.3 cm). In the second group, there were
      124 patients, and they were treated with combined US-guided percutaneous
      evacuation and medical therapy. In them, 22 patients have a collected abscess
      with a diameter less than 10 cm ranged from 4.9 to 9.5 cm (mean 7.4 cm), and 102
      patients have a collected abscess with a diameter equal or greater than 10 cm
      (measured 10 cm to 27.5, mean 15.3). There were twenty four patients in the last
      group, they were treated by open chirurgical drainage because they have an
      abdominal ruptured abscess. The results with each form of therapy were assessed
      clinically and by abdominal ultrasound.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283414
TI  - [Gastric leiomyosarcoma. Ultrasonographic endoscopy and MRI].
AB  - Leiomyosarcoma of the stomach is an unfrequent tumor, for which the prognosis is
      better than for cancer of the stomach. Its development is often subserosal, thus
      explaining its clinical latency and its large volume at the time of diagnosis.
      While many publications report about the merits of conventional imaging for this
      type of pathology, few authors have considered ultrasonographic endoscopy, and
      even fewer magnetic resonance imaging. The authors present one case for which
      these two recent techniques were implemented, as well as a review of the
      literature.

PMID- 8283415
TI  - [Ectopic pregnancy in tropical climate. An ultrasonographic study of 93
      consecutive cases].
AB  - BACKGROUND AND PURPOSE: Ectopic pregnancy (EP) is common in Cameroon, and
      incidence is increasing. Ultrasound (US), has been shown to play a key role in
      its diagnosis, particularly when the transvaginal (TV) route is used. The purpose
      of our work is to describe sonographic features of EP, and to assess the role of
      the transvaginal route in the diagnosis of this disease in our environment.
      PATIENTS AND METHODS: The study was prospectively carried in the US unit of the
      Yaounde University teaching Hospital (Cameroon) during a 2 year period. 502
      patients aged 14 to 45 were included because of clinical suspicion of EP. The
      criteria for sonographic diagnosis of EP were the presence of an embryo outside
      the uterus, a ring-like adnexal structure, or complex adnexal mass separate from
      the ovaries, in conjunction with free peritoneal fluid. The EP was considered
      ruptured if significant fluid was found in the upper peritoneal recesses. The
      diagnosis was confirmed by laparoscopy or laparotomy. RESULTS: Ninety six
      patients were found to have an EP. 56 patients had only TV pelvic US, 13 had both
      TV and TA routes, and 24 patients had only TA pelvic US. The mean age was 29
      years (interval: 17-42). The main clinical findings included: pain (88%),
      amenorhea (84%), bleeding (72%), cardio-vascular instability (14%), pelvic mass
      (9%). The pregnancy was tubal for 93 patients, and abdominal for 3. It was
      ruptured for 46 (49%). Adnexal abnormalities were present for 86 patients (92%).
      These were a gestational sac (78%) with a living embryo in 31 patients (33%), or
      a complex adnexal mass (15%). Uterine findings (40%) included: endometrial
      thickening (20%), pseudosac (19%), fibroids (6%). An ovarian cysts was present
      for 10 patients. As a rule, TV route delineated all these findings better than
      the TA route. CONCLUSION: An exceptionally high proportion of EP was seen after
      rupture in this study. Our recommendations include: educate patients to seek
      immediate medical advice for any missed period associated with pain, increase
      health providers' awareness of EP, and promote availability of TVUS.

PMID- 8283416
TI  - [Smith-Lemli-Opitz syndrome type II. Contribution of imaging].
AB  - Smith-Lemli-Opitz syndrome, type II, is a very rare congenital condition which
      has been fatal in all reported cases. The imaging findings can be diagnostic. A
      rapid and accurate diagnosis is very important to the effected infant and the
      parents in this autosomal recessive condition.

PMID- 8283417
TI  - [Memories of a X-ray bulb. Introduction. 1: the office of a radiologist].

PMID- 8283418
TI  - The osteocutaneous upper arm flap for mandibular reconstruction.
AB  - The authors present the osteocutaneous upper arm flap as useful in segmental
      microsurgical mandibular reconstructions. This flap presents several advantages:
      easy and rapid dissection; a long and reliable pedicle; excellent segmental blood
      supply to the bone, allowing multiple osteotomies; remarkable mobility of the
      skin paddle relating to the underlying bone; and minimal donor-site morbidity.
      Among its few disadvantages are that the bone is predominantly cortical, and the
      bone shaft cannot exceed 11 x 2 cm. Nevertheless, this flap is an excellent
      alternative to conventional procedures, when a segmental reconstruction,
      requiring short bone segments and skin, is required. Eight consecutive clinical
      cases have been successfully treated and are reported.

PMID- 8283419
TI  - Is early bone scintigraphy a reliable method to assess the viability of
      vascularized bone transplants?
AB  - This clinical study reveals radiomarker uptake in corticocancellous non
      vascularized bone grafts as early as 3 days postoperatively. It therefore calls
      into question whether seventh-postoperative-day bone scintigraphy is a reliable
      method for determining the viability of vascularized bone grafts.

PMID- 8283420
TI  - Vascularized nerve tube: an experimental alternative for vascularized nerve
      grafts over short gaps.
AB  - Multilayered tubes fabricated from human amnion were placed subcutaneously and/or
      longitudinally in contact with an axial artery and vein in rats. Histologic
      evaluation at the third postoperative week showed that the tubes had incorporated
      with the surrounding fibrovascular tissue. New capillary formation within the
      tube wall was well demonstrated by microangiography. Vascularized amnion tubes
      were then used to bridge a 1-cm-long femoral nerve gap in an artificially
      created, relatively avascular bed in rats. An avascular bed was created by
      wrapping the corresponding nerve segment with a thin silicone sheet. After 3
      months, nerve regeneration was assessed using morphometric analysis. The
      vascularized amnion conduits showed comparable nerve regeneration to vascularized
      nerve grafts (p > 0.05), and superior nerve regeneration when compared to
      nonvascularized amnion conduits and nonvascularized nerve grafts as well (p <
      0.05). This suggests that, in the rat model, a conduit can be neovascularized and
      used as a prefabricated tissue, to bridge short nerve gaps in a compromised bed.

PMID- 8283421
TI  - Comparison of macropore, semipermeable, and nonpermeable collagen conduits in
      nerve repair.
AB  - Twelve rabbits were used to study functional nerve regeneration through
      macropore, semipermeable, and nonpermeable collagen conduits. Each animal
      underwent a 10-mm bilateral resection of posterior tibial nerve. Lesions were
      repaired with a macropore collagen tube in one leg, and with a semipermeable or a
      nonpermeable collagen tube contralaterally. Functional nerve regeneration was
      evaluated at 6 and 12 weeks post-repair periods. Functional recovery was assessed
      by electrophysiologic analysis of nerve conduction velocity, amplitude of nerve
      action potential, amplitude and area of muscle action potential, and by
      quantitative and qualitative histologic analysis of myelinated nerve fibers from
      the distal nerve stumps. The macropore-collagen-tube group showed significantly
      greater functional recoveries than semipermeable or nonpermeable collagen-tube
      groups, based on electrophysiologic and histologic analyses.

PMID- 8283422
TI  - Double vascularized fibulas for reconstruction of large tibial defects.
AB  - Vascularized fibular grafts have proven to have many advantages over
      nonvascularized transplants for treatment of large segmental bone defects in the
      extremities. Fibulas are typically impacted into the medullary canal and fixed
      with wires or screws. Consolidation has often been delayed and full weightbearing
      was only possible after graft hypertrophy, usually 12 to 18 months after
      reconstruction. In order to shorten the time of consolidation and to achieve
      early full weightbearing, the authors propose a sound biomechanical
      reconstructive concept: a) stable but not devascularizing osteosynthesis of the
      osteotomy to shorten the time of consolidation; b) a double-strut fibular graft
      that yields enough strength for early weightbearing, without the need for bone
      hypertrophy; and c) additional cancellous bone grafts, to enhance the long-term
      stability of the reconstruction. Seven patients with tibial defects ranging
      between 6 and 17.5 cm were treated according to this concept. In four cases, free
      vascularized fibula was transferred first. Six weeks later, a vascularized,
      ipsilateral fibula-pro-tibia procedure was done, and the space between the
      fibulas was filled with cancellous bone grafts. In three patients, a free,
      vascularized, double-barrel, fibula transfer was done, since the tibial defect
      was less than 10 cm. Cancellous bone grafts between the fibulas were added only 6
      weeks later. In five cases, the free fibula transfer was combined with a
      latissimus dorsi myocutaneous flap. In six patients, healing was uneventful. In
      one patient, hypoperfusion of the lower extremity and the vascularized grafts
      eventually resulted in a below-knee amputation. In all six successful cases,
      union resulted within 3 months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283423
TI  - Blood flow of segmentally divided and folded nerve.
AB  - The integrity of the blood supply to three equal segments of a nerve was
      determined, after the nerve was cut and folded but with its epineurial
      vasculature remaining intact. A 7.5-cm length of the rabbit sciatic nerve was
      elevated on a single pedicle. The epineurium was slit longitudinally, and the
      nerve fascicles were exposed, cut transversely into three equal segments, and
      then folded so that they were parallel. This is equivalent to a vascularized,
      folded, nerve graft in the clinical setting. Blood flow was quantified with
      microspheres in six rabbits, both after elevating the nerve and then again after
      it had been cut and folded. Mean blood flows in the three segments ranged from
      4.4 to 6.2 ml/min/100 g after elevation, and from 4.7 to 8.0 ml/min/100 g after
      cutting and folding. Dividing and folding of the nerves did not significantly
      decrease blood flow in any of the nerve segments. The results support this
      technique as a valid method for vascularized, cable, nerve grafting.

PMID- 8283424
TI  - Fabrication of vascularized bone grafts using ceramic chambers.
AB  - The present study was designed to create a vascularized bone graft combining the
      osteogenetic potential of bone marrow cells, and vascular bundle implantation in
      a hydroxyapatite chamber, using New Zealand white rabbits. A hydroxyapatite
      chamber was molded into a cylindrical shape, and hydroxyapatite fillers were
      soaked in an autogenous bone-marrow-cell suspension at a concentration of 1.6 x
      10(8)/ml. In one group, the implant was packed with allogenic demineralized bone
      matrix powder (DBM) and implanted in the mid-thigh subcutaneously, with the
      epigastric vessels running through the chamber. In a second group, the chamber
      with bone marrow cells and DBM was implanted subcutaneously, without vascular
      bundle implantation. The control group consisted of a chamber without DBM, soaked
      in venous blood and implanted in the opposite thigh, with the epigastric vessels
      running through the chamber. Cross-sectional bone area and mineral apposition
      rate were measured, in addition to newly-formed vessels. After 3 weeks, chambers
      implanted with bone marrow cells and DBM demonstrated consistent bone formation
      in the pores of the chamber walls and within the chambers. No evidence of bone
      formation was noted in the chambers soaked with venous blood. The results
      indicated that vascular-bundle implantation promoted earlier bone formation with
      neovascularization in the chambers with bone-marrow cells and DBM.
      Microangiograms revealed vascular connections between the vascular bundle and
      soft tissue surrounding the chamber through newly-formed vessels in the chamber
      wall. These findings support the concept of creating a preformed vascularized
      bone graft, to reconstruct segmental bone defects.

PMID- 8283426
TI  - Growth of small follicles and concentrations of FSH during the equine oestrous
      cycle.
AB  - The temporal associations between increases in FSH and growth of small follicles
      (2-20 mm) were studied during one oestrous cycle (ovulation to ovulation) in 15
      horse mares. Follicular diameters were obtained ultrasonically. For each day,
      follicles were combined for both ovaries, grouped from largest to smallest
      (excluding dominant follicles), and divided into three to five tiers of six
      follicles for each mare (for example: tier 1, six largest follicles; tier 2, next
      six largest follicles). A significant increase in mean diameters followed by a
      significant decrease was used to define a follicular wave within each of the
      tiers for each mare. Day of wave emergence was defined by the lowest mean
      preceding the increase. Follicular waves were detected in all tiers in each mare.
      The number of detected waves per interovulatory interval was greater (P < 0.05)
      for tier 5 (2.8 +/- 0.4) than for tier 1 (1.1 +/- 0.1) and tier 2 (1.9 +/- 0.3).
      A primary follicular wave (wave giving rise to the dominant follicle that
      ovulated during the subsequent oestrus) was identified in tier 1 in all mares.
      Composite profiles were constructed by normalizing each tier for each mare to the
      mean day of emergence of the primary wave for all mares, as detected in tier 1.
      The composite follicular profiles for the five tiers were approximately parallel;
      the follicles for tiers 2-5 emerged on the mean day of emergence of the primary
      wave (6 days after ovulation). The range of follicular means on the common day of
      wave emergence was 3 mm (tier 5) to 12 mm (tier 1).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8283425
TI  - Effect of exogenous melatonin and exposure to a ram on the time of onset and
      duration of the breeding season in Icelandic sheep.
AB  - Icelandic ewes, living under natural photoperiod conditions, were treated with
      daily melatonin (2.5 and 10 mg day-1) for 75 days from the autumn equinox. Ewes
      were also exposed to a ram from the autumn equinox until the end of June, for 30
      days from the end of the anoestrous period (30 October), and from 11 December for
      30 days during the oestrous season. Blood samples were collected three times per
      week from September until the cessation of seasonal ovarian activity and assayed
      for progesterone. Melatonin treatment did not significantly alter the time of
      onset or the duration of the breeding season compared with control ewes. There
      were no significant changes in luteal activity due to melatonin. Ewes exposed to
      a ram from the autumn equinox had a longer breeding period than did control ewes
      owing to earlier onset of ovarian activity. Exposure to a ram had a significant
      effect on luteal activity during the first seasonal ovarian cycle. It is
      suggested that insignificant response to melatonin treatments and slow response
      to ram exposure in Icelandic sheep were caused by entrainment of the reproductive
      endocrine system by the large seasonal changes in the photoperiod.

PMID- 8283427
TI  - Dominance rank and reproductive maturation in male rhesus macaques (Macaca
      mulatta).
AB  - The timing of reproductive maturation in females has been linked to differences
      in dominance status and exposure to males, but less information is available
      regarding the effect of dominance rank and exposure to females on the pace of
      reproductive maturation in males. A two-year study of a cohort of nine male
      rhesus macaques was undertaken to document potential social factors influencing
      variation in rates of reproductive maturation. The males lived in a large
      heterosexual group housed in a 0.3 ha outdoor enclosure. Every four weeks the
      focal subjects were isolated from the group to collect morphometric measurements
      and blood samples. The results revealed that dominance rank was not significantly
      correlated with average testosterone concentrations during the mating season.
      However, the highest ranking adolescent male had higher testosterone
      concentrations at a younger age, earlier in the mating season, and for a longer
      duration than did the lowest ranking male. Relative testicular weight was
      significantly correlated with dominance rank during the premating season, but not
      the postmating season, among adolescent males. The highest ranking adolescent
      male also engaged in more affiliative and sexual activity with nonkin, sexually
      receptive females than did lower ranking conspecifics. These patterns of
      development provide evidence that high dominance status accelerated reproductive
      maturation in male rhesus macaques.

PMID- 8283428
TI  - Uptake of relaxin in the uterus and cervix of rats in vivo: influence of ovarian
      steroids and tolerance.
AB  - The influence of oestradiol benzoate and progesterone treatment and of tolerance
      to relaxin on the uptake of 125I-labelled porcine relaxin by reproductive tissues
      was investigated in anaesthetized female rats. In ovary-intact rats, 125I
      labelled relaxin uptake increased with time in reproductive tissues and in
      tissues concerned with metabolism and excretion. Administration of 50 micrograms
      unlabelled porcine relaxin before injection of 125I-labelled relaxin
      significantly reduced uptake of 125I-labelled relaxin into the uterus and cervix,
      but had no effect on uptake of 125I-labelled relaxin into other tissues,
      indicating that specific uptake of relaxin was occurring in the uterus and
      cervix. In ovariectomized rats, treatment with oestradiol benzoate or oestradiol
      benzoate plus progesterone for 1 day did not significantly increase uterine or
      cervical 125I-labelled relaxin uptake compared with corn oil-treated rats, but
      induced a significant increase in uterine uptake of 125I-labelled relaxin after
      treatment for 2 days. Induction of tolerance to relaxin by i.v. infusion of a
      high dose of relaxin significantly reduced uterine and cervical uptake of 125I
      labelled relaxin at 3 h after termination of infusion compared with saline
      infused rats. By 12 h after termination of infusion, 125I-labelled relaxin uptake
      in the uterus and cervix was similar in saline-infused rats and in rats given an
      infusion of relaxin. Infusion of glibenclamide (20 mg kg-1) did not influence
      uterine or cervical uptake of 125I-labelled relaxin; however, treatment with
      phentolamine (10 mg kg-1) significantly reduced 125I-labelled relaxin uptake in
      uterus, bladder and jejunum. This study demonstrates that steroid hormone
      treatment and tolerance modulate relaxin uptake in reproductive tissues.

PMID- 8283429
TI  - A new method for cryopreservation of mouse spermatozoa.
AB  - A new method for the cryopreservation of mouse spermatozoa was developed using a
      modified egg-yolk TES-Tris diluent containing 0.1% sodium lauryl sulfate and
      1.25% (v/v) glycerol (mouse sperm cryoprotectant, MSC). Epididymal spermatozoa
      collected from 10-week-old CBA males were frozen at a rate of 5 degrees C min-1
      to 4 degrees C and 50 degrees C min-1 to -70 degrees C using a programmable cell
      freezer. A percentage of the spermatozoa (25%) regained motility after thawing.
      In vitro fertilization with frozen-thawed spermatozoa resulted in 50% of oocytes
      developing to the two-cell stage. These two-cell embryos were placed in the
      oviducts of pseudopregnant recipients (C57BL/CBA) and 16% developed to be viable
      fetuses, or in the oviducts of pregnant recipients (MF1) and 17% developed to
      live offspring.

PMID- 8283430
TI  - Ca(2+)-related changes in the capacitation state of human spermatozoa assessed by
      a chlortetracycline fluorescence assay.
AB  - Chlortetracycline (CTC) fluorescence patterns were used to assess Ca(2+)-related
      changes in the capacitation state of human spermatozoa incubated under conditions
      that would affect their intracellular Ca2+ levels. Initial experiments were
      designed to identify consistently occurring patterns and to correlate these with
      acrosomal status. Incubation for up to 1 h with the ionophore A23187 (10 mumol l
      1), known to promote capacitation and acrosomal exocytosis, allowed the
      identification of three different CTC staining patterns which were very similar
      to those described for mouse spermatozoa. For this reason, they were given the
      same nomenclature: 'F'-characteristic of uncapacitated, acrosome-intact cells;
      'B'-characteristic of capacitated, acrosome-intact cells; and 'AR'-characteristic
      of capacitated, acrosome-reacted cells. The distribution of the three patterns in
      the ionophore-treated suspensions was very different from that in control
      suspensions treated with dimethylsulfoxide only, with a significantly higher
      proportion of cells displaying the B and AR patterns and a significantly lower
      number of cells displaying the F pattern in the ionophore-treated group at all
      times. A strong concordance was found between the acrosomal status of cells
      determined using both CTC and fluorescein-conjugated Pisum sativum agglutinin
      (PSA) staining methods on the same cells. Verification of PSA staining patterns
      with acrosomal status was obtained by means of transmission electron microscopy.
      The proportion of cells with uniform fluorescence in the acrosomal region
      correlated with acrosome-intact cells; those with only equatorial segment
      staining correlated with fully-reacted cells, and those exhibiting equatorial
      fluorescence and patchy fluorescence over the rest of the acrosomal region
      correlated with cells in intermediate stages of exocytosis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8283431
TI  - Preferential survival of mice expressing the Qa-2 antigen.
AB  - The Ped gene, a gene that influences the rate of embryonic cleavage division,
      birth weight, litter size and weaning weight, is at least partially encoded by
      gene(s) that specify the Qa-2 antigen. Two congenic strains of mice, B6.K1 (Qa-2
      negative) and B6.K2 (Qa-2 positive), which differ only at the Q region of the
      mouse major histocompatibility complex (MHC), were tested for the effect of the
      presence or absence of Qa-2 antigen on litter size, duration of gestation and
      embryo survival. It was confirmed that B6.K1 (Qa-2 negative) mice have smaller
      litters than do B6.K2 (Qa-2 positive) mice. In addition, the duration of
      gestation for the B6.K1 mice was found to be longer than the duration of
      gestation for the B6.K2 mice. Finally, a comparison of the relative survival of
      Qa-2-positive and Qa-2-negative mice in a single uterine environment showed the
      preferential survival of mice expressing the Qa-2 antigen. Thus, the presence of
      Qa-2 antigen appears to be advantageous for reproductive success.

PMID- 8283432
TI  - Novel organization of the spermatozoon in two species of murid rodents from
      southern Asia.
AB  - The morphology and structural organization of unusual spermatozoa from two
      species of bandicoot rats (Bandicota spp) from Southern Asia were studied with
      the light and transmission electron microscope. Unlike those described for nearly
      all other eutherian species the heads of Bandicota savilei and B. indica
      spermatozoa were bulbous or globular in shape and had no narrow uniformly defined
      apex nor a clearly delineated perforatorium. The nucleus, which had one or more
      prominent vacuoles, was capped by a huge, bulky, acrosome with no obvious
      morphologically recognizable equatorial segment. The postacrosomal dense lamina
      was extremely short and a posterior ring lay anterior to the caudal pole of the
      nucleus. In addition, the tail of the spermatozoon was only 28-45 microns in
      length. The organization of the spermatozoon of these two species of Bandicota is
      thus quite unlike that described for any other murid rodent or even mammalian
      species. Its highly divergent features suggest that the processes of zona
      penetration and incorporation of the fertilizing spermatozoon into the egg may
      differ markedly from those of all eutherians so far investigated.

PMID- 8283433
TI  - Quantitative analysis of morphological modifications of day 6.5 horse embryos
      after cryopreservation: differential effects on inner cell mass and trophoblast
      cells.
AB  - Sixteen embryos were recovered nonsurgically at day 6.5 after induced ovulation
      from Welsh pony mares and were evaluated for cellular changes that occur because
      of exposure to the cryoprotectant with or without the freeze and thaw process.
      Day 6.5 horse embryos were either (i) frozen and thawed using glycerol as
      cryoprotectant (n = 6), (ii) given only the glycerol treatment (n = 5), or (iii)
      washed in phosphate-buffered saline (PBS) the same number of times as in the
      glycerol treatment (n = 5). After treatments, embryos were incubated in Minimum
      Essential Medium (MEM), supplemented with BSA, glutamine, antibiotics and
      buffered with Hepes, for 1 h for one embryo per group and for 6 h for the others.
      After histological fixation, embryos were serially sectioned. On observation by
      light microscopy, the total numbers of interphasic, mitotic and pycnotic nuclei
      of each embryo were counted. Electron microscopy was used to evaluate the damage
      to the fine structure of intracellular organelles. The proportion of mitotic
      cells did not differ among groups (control: 2.3%; glycerol-treated: 1.8%; frozen
      thawed: 1.3%). There were significant differences in the proportion of pycnotic
      cells both between control (12.8% +/- 5.6) and glycerol-treated embryos (39.4% +/
      15.9) (P < 0.05) and between control and frozen-thawed embryos (42.2% +/- 14.9)
      (P < 0.001), but no difference was found between treated embryos (glycerol
      treated and frozen-thawed embryos). Degenerated cells were not localized in the
      same place in each embryo and no ultrastructural alteration was uniformly
      observed among every embryo of each group, but inner cell mass (ICM) cells were
      affected most by treatments (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283434
TI  - Detection of altered acrosomal physiology of cryopreserved human spermatozoa
      after sperm residence in the female reproductive tract.
AB  - At least some of the spermatozoa that remain motile following cryopreservation
      have sustained sublethal damage that reduces their functional capacity in vivo.
      Although it is believed that acrosomal damage is partly responsible for impaired
      sperm function in vivo, direct evidence for this hypothesis is lacking because
      spermatozoa have not been collected from the female reproductive tract for
      evaluation. In the study reported here, cervical mucus was collected from women
      24 h after artificial insemination by cervical cup. For both cryopreserved and
      nonfrozen inseminates, spermatozoa within the cervical mucus and spermatozoa that
      migrated out of mucus into culture medium (t = 1 h) were viable and had intact
      acrosomes. However, although nonfrozen spermatozoa did not initially respond to
      induction of the acrosome reaction with follicular fluid, a significant
      proportion of cryopreserved spermatozoa did respond. These results demonstrate
      that cryopreservation increases the acrosomal lability of spermatozoa residing in
      the female reproductive tract. An in vitro test was developed to detect this form
      of cryodamage. Sperm-free mucus was collected before insemination and spermatozoa
      from the inseminate were allowed to swim into this column of mucus in vitro.
      Spermatozoa recovered from this mucus sample were compared with spermatozoa from
      the paired sample collected from the cervix 24 h later. This in vitro test could
      detect acrosomal lability in cryopreserved semen samples, and this approach may
      prove valuable for studying sublethal cryodamage to the acrosome.

PMID- 8283435
TI  - Evidence that androgens are involved in atresia and anovulation induced by
      antiprogesterone RU486 in rats.
AB  - Administration of antiprogesterone RU486 to female cyclic rats results in
      blockade of ovulation associated with both a decreased ovulatory release of LH
      and an increased rate of follicular atresia. These rats also exhibit increased
      LH:FSH and testosterone:oestradiol ratios in serum during the period of
      follicular development as well as an increase in serum concentrations of
      prolactin that can be suppressed by a dopamine agonist. The increase in either
      prolactin or testosterone concentrations as well as the relative deficiency in
      FSH might be responsible for the increase in follicular atresia. The present work
      evaluated the involvement of LH, FSH, prolactin and testosterone in follicular
      atresia and in blockade of ovulation induced by RU486 in the cyclic rat. Although
      bromocriptine treatment did not modify the blockade of ovulation induced by
      RU486, unilateral ovariectomy at metoestrus and anti-androgen flutamide treatment
      reversed, in part, the effects of RU486 on both follicular development and
      ovulation. The combined increase in FSH serum concentration during dioestrus
      induced by unilateral ovariectomy and the treatment with flutamide had no
      additive effects. Furthermore, treatment with a superovulatory amount of hFSH did
      not reverse the effects of RU486. Moreover, unilateral ovariectomy halved
      testosterone serum concentrations and flutamide treatment had no effect on LH and
      FSH concentrations in RU486-treated rats. It was therefore concluded that
      androgens play a role, at least in part, in the process of follicular atresia
      induced by RU486.

PMID- 8283436
TI  - Effects of oxytocin and uterine and luteal prostaglandins on the functional
      regression of the corpus luteum in pseudopregnant rats.
AB  - The effects of oxytocin on luteal regression in the pseudopregnant rat and
      whether the luteolytic effect of oxytocin could be blocked by an oxytocin
      receptor antagonist were investigated. We determined the temporal relationship
      between the effects of oxytocin on the duration of pseudopregnancy and
      concentrations of progesterone in plasma, and uterine and luteal prostaglandin
      concentrations. Pseudopregnancy was induced in normal cyclic rats by
      gonadotrophin treatment. On day 6 of pseudopregnancy, rats were assigned to one
      of three groups. One group was given oxytocin, 500 mU s.c., twice a day for three
      days. A control group was given saline injections. A third group was given the
      same dose of oxytocin and an oxytocin receptor antagonist,
      [Pen1,Phe(Me)2,Thr4,Orn8]oxytocin, 300 micrograms day-1, delivered by micro
      osmotic pumps for the same three-day period. Rats were either observed to
      determine the duration of pseudopregnancy, or killed on days 2, 6, 7, 9, 11 and
      13 of pseudopregnancy for measurements of plasma concentrations of progesterone
      and luteal and uterine PGF2 alpha and PGE2 concentrations by radioimmunoassays.
      Oxytocin injections shortened the duration of pseudopregnancy from the mean of
      13.5 +/- 0.3 days for the control group to 11.5 +/- 0.3 days for the oxytocin
      treated group (P < 0.01). The oxytocin-induced shortening of pseudopregnancy was
      associated with a premature functional regression of the corpus luteum. Both
      luteal and uterine PGF2 alpha concentrations were found to increase with
      luteolysis and reached peak values before the return of oestrus. However, only
      uterine PGF2 alpha synthesis was stimulated by oxytocin treatment. There was no
      significant increase in uterine or luteal PGE2 synthesis during
      luteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283437
TI  - A biphasic pattern of 45Ca2+ uptake by mouse spermatozoa in vitro correlates with
      changing functional potential.
AB  - Mouse sperm capacitation in vitro, leading to hyperactivated motility, acrosomal
      exocytosis and rapid fertilization, takes approximately 120 min in a medium
      containing sufficient Ca2+. During that period, spermatozoa incubated in 45Ca2+
      exhibited a biphasic pattern of Ca2+ uptake, with the first and lower peak
      occurring from 10 to 50 min and the second and higher peak from 60 to 90 min.
      When the exogenously supplied glucose was reduced from 5.56 mmol l-1 to 5.56
      mumol l-1, the latter supporting capacitation but not fertilization, only the
      first peak of 45Ca2+ uptake was observed. Increasing the glucose to a millimolar
      concentration produced a second peak of uptake. We therefore propose that the
      first phase of 45Ca2+ uptake is associated with capacitation and the second phase
      with acrosomal exocytosis, which are both necessary prerequisites for
      fertilization. In micromolar glucose the rate of 45Ca2+ uptake during the first
      30 min was 47% higher than in millimolar glucose, suggesting that the former
      conditions might promote a precocious rise in the intracellular Ca2+
      concentration ([Ca2+]i) and hence accelerate capacitation. This hypothesis was
      confirmed by demonstrating both significantly accelerated transition from the
      uncapacitated F pattern of chlortetracycline (CTC) fluorescence to the
      capacitated B and AR patterns and significantly higher fertility in vitro in
      suspensions preincubated for 30 min in micromolar glucose, compared with those
      maintained continuously in millimolar glucose. These results suggest that an ATP
      dependent mechanism, for example a Ca(2+)-ATPase, may be involved in maintaining
      a low [Ca2+]i. In micromolar glucose, available ATP would be limited and hence
      the ATPase activity would decline, allowing [Ca2+]i to rise.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8283438
TI  - Arachidonic acid 15-lipoxygenase and traces of E prostaglandins in purified human
      prostasomes.
AB  - Human spermatozoa are associated with arachidonate 15-lipoxygenase activity. This
      activity could be due to 15-lipoxygenase in small organelles (prostasomes), which
      are known to bind hydrophobically to germ cells. This possibility was assessed by
      separating prostasomes from human spermatozoa by differential centrifugation and
      purifying them by gel filtration (Sephadex G-200). Purified prostasomes
      metabolized [1-14C]arachidonic acid to 15(S)-hydroxyeicosatetraenoic acid as
      determined by reverse phase and by chiral phase HPLC and by gas chromatography
      mass spectrometry. Biosynthesis of prostaglandins could not be detected, but the
      prostasomes contained trace amounts of the four major E prostaglandins of human
      seminal fluid (3.6 nmol mg-1 of prostasomal protein). Arachidonic acid 15
      lipoxygenase has recently been implicated in the acrosome reaction of bull
      spermatozoa and it may have a similar function in the acrosome reaction of human
      spermatozoa.

PMID- 8283439
TI  - Hormonal control of ovarian phospholipase A2 activity in rats.
AB  - The ovulatory effect of LH is mediated by prostaglandins, the synthesis of which
      involves prostaglandin synthetase and phospholipase A2 (PLA2). It is known that
      the activity of the former is regulated by LH in the ovary and the objective of
      this study was to establish the presence of PLA2 in the rat ovary and to
      determine whether LH has a role in regulating its activity. We demonstrated the
      presence of a calcium-dependent PLA2 in rat ovaries and shown that, in adult
      rats, the activity of this enzyme rises significantly on the evening of pro
      oestrus (at the expected time of the preovulatory LH surge) and remains high over
      the evening hours, declining by the next morning. Furthermore, pregnant mares'
      serum gonadotrophin (PMSG), which when injected into 28-day-old rats induces an
      LH surge 54 h later, caused at the same time, a rise in ovarian PLA2 activity.
      Administration of 5 micrograms oestradiol benzoate S.C. to 25-day-old rats
      stimulated ovarian PLA2 activity 54 h later, at the time of the oestrogen-induced
      LH surge. Human chorionic gonadotrophin (hCG) had no effect on circulating
      concentrations of LH, FSH or oestradiol but stimulated ovarian PLA2 activity 2 h
      later. Gonadotrophin-releasing hormone (GnRH) given to 25-day-old rats (either
      untreated or primed with 0.5 mg oestradiol benzoate) had no effect on ovarian
      PLA2 activity but the resulting LH surge may have been too transient.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8283440
TI  - Differential effects of adrenalectomy on the prolactin-induced suppression of LH
      and FSH secretion after castration in male rats.
AB  - Hyperprolactinaemia inhibits gonadotrophin secretion in males and females of many
      species. The aim of this study was to determine the role of the adrenal gland in
      mediating the inhibitory effects of prolactin by contrasting the effects of acute
      hyperprolactinaemia on LH and FSH secretion in adrenal-intact and
      adrenalectomized rats with and without physiological corticosterone replacement.
      Adult male rats were administered purified ovine prolactin every 12 h (2.4 mg per
      injection s.c.) beginning at the time of castration. Blood samples were collected
      every 3 h for 36 h, then every 12 h until 10 days after castration. Ovine
      prolactin significantly reduced LH secretion in all groups from approximately 15
      to 48 h after castration. In contrast, plasma FSH concentrations were reduced by
      ovine prolactin from 21 to 48 h only in the adrenal-intact rats and not in the
      adrenalectomized or adrenalectomized plus corticosterone groups. In all groups,
      ovine prolactin inhibited endogenous prolactin secretion in rats by short-loop
      autofeedback as soon as 3 h after the first ovine prolactin injection and
      throughout the 10 days of the study. Adrenalectomy per se, with or without
      corticosterone replacement, also had a differential effect on LH and FSH
      secretion after castration, causing only a transient delay in the rise in LH
      after castration, but inducing a significant and long-lasting inhibition of FSH
      secretion. The results demonstrate that ovine prolactin-induced suppression of LH
      secretion after castration occurs with or without the adrenal glands. Suppression
      of FSH secretion after castration by ovine prolactin, however, may involve an
      adrenal component.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283441
TI  - Silastic implants for delivery of oestradiol to mice.
AB  - Silastic implants containing oestradiol were developed for delivering a range of
      physiological concentrations of oestradiol to mice over long periods. The
      implants consisted of discrete lengths of Silastic tubing containing oestradiol
      in arachis oil, with a small reservoir of the oestradiol solution at either end
      of the implant. Studies showed that the release of oestradiol in vitro was
      proportional to the concentration of steroid within the implant. Implants
      containing oestradiol at concentrations from 1 to 100 micrograms ml-1 could
      induce biological responses in ovariectomized mice, ranging from minimal effects
      on uterine weight and vaginal smears to supraphysiological increases in uterine
      weight and rapid vaginal cornification. Studies of uterine vascular permeability
      indicated that significant effects occurred within a few hours of initial
      placement of the implant. These results suggest that the design of the Silastic
      implants described in this study provides a useful method for delivering
      controlled and easily manipulated physiological doses of oestradiol to mice.

PMID- 8283442
TI  - Evidence that primer pheromones do not cause social suppression of reproduction
      in male and female naked mole-rats (Heterocephalus glaber).
AB  - The role of chemical cues in mediating the reproductive suppression of
      nonbreeding males and females in colonies of naked mole-rats (Heterocephalus
      glaber) was examined by comparing reproductive activation in isolated nonbreeders
      with that of isolated nonbreeders maintained in olfactory and gustatory contact
      with their parent colony. Animals were either removed from their colony and
      paired directly with a member of the opposite sex from the same colony, or were
      removed, housed singly for 40 days, and then paired with a member of the opposite
      sex from the same parent colony that had also been housed singly for 40 days.
      Approximately half of these separated animals received a daily transfer of soiled
      bedding and litter from their parent colony. In females, there was no significant
      difference between the control and bedding transfer group, in the time taken from
      separation to the first sustained increase of urinary progesterone above 2 ng mg
      1 Cr indicative of the luteal phase of an ovarian cycle (7.8 +/- 2.6 versus 9.4
      +/- 2.0 days, respectively). In both control and bedding transfer groups, singly
      housed females commenced ovarian cyclicity, revealing that the presence of a male
      was not required for reproductive activation and ovulation. In males,
      concentrations of both urinary testosterone and plasma LH increased after
      separation from their parent colonies in both control and bedding transfer
      groups, to reach values equivalent to those of breeding males.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8283443
TI  - Effect of immunization against LHRH on isoforms of LH in the ovine pituitary.
AB  - The role of LHRH in modulating intrapituitary LH content as well as the
      distribution of LH among its isoforms was examined in sheep. Rams (n = 3) and
      wethers (n = 6) were actively immunized against an LHRH-human serum globulin
      conjugate. Pituitaries collected from these animals plus pituitaries from
      corresponding numbers of nonimmunized rams and wethers were extracted with a
      buffered saline solution containing protease inhibitors. Immunization markedly
      reduced total amounts of immunoreactive LH in the pituitary. An aliquot of each
      pituitary extract was desalted by flow dialysis against water and chromatofocused
      on a pH 10.5-7.0 gradient. Concentrations of LH in chromatofocusing fractions
      were determined by radioimmunoassay. LH in pituitary extracts resolved into nine
      peaks during chromatofocusing which were coded with letters beginning with the
      most basic isoform. The percentage of LH as the two most basic isoforms, A' and
      B, was similar (P > 0.05) in all treatment groups. Isoform H constituted a higher
      percentage (P < 0.05) of the LH in both castrate groups. Nonimmunized wethers had
      higher percentages of isoforms C, D and E (P < 0.05) and lower percentages (P <
      0.05) of the acidic isoforms (coded as peak Z herein) than did other treatment
      groups. Thus, castration shifted the pattern of intrapituitary isohormones
      towards the more basic forms. Nonimmunized rams had a higher percentage (P <
      0.05) of isoform G than did other groups. Isoform F, the most abundant isoform,
      was present as a higher percentage (P < 0.05) in immunized rams and wethers than
      in nonimmunized animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283444
TI  - Uterine histology of the dasyurid marsupial, Antechinus stuartii: relationship
      with differentiation of the embryo.
AB  - Uterine samples from Antechinus stuartii on days 1, 4, 6, 8, 11, 13, 15, 18, 21
      and 23 after ovulation were examined histologically. Animals were pregnant,
      nonpregnant and unmated, or nonpregnant and mated but found to have only
      unfertilized eggs on autopsy. The histological parameters used were thickness of
      the myometrium, endometrial stroma, and endometrial epithelium, and density of
      uterine stromal glands and of lymphocytes at the endometrial basal lamina.
      Overall, the fluctuation patterns of these parameters were superficially similar
      between pregnant and nonpregnant animals (mated or unmated). However,
      statistically significant differences were detected between pregnant and unmated
      nonpregnant animals in every parameter examined at nearly every time point except
      day 13. Comparison of these results with known data on embryonic stages, corpus
      luteum development and plasma progesterone concentrations revealed that the
      gravid uterus underwent histological changes co-incident with changes in both
      progesterone concentration and developmental delay or embryonic arrest. It was
      concluded that the uterus mediates progesterone-driven changes in embryonic
      developmental rate. Although determination of number of lymphocytes provided
      inconclusive evidence of cellular immunity against embryos, the possibility that
      embryonic signalling to the uterus occurs is discussed.

PMID- 8283445
TI  - Measurement of faecal steroids for monitoring ovarian function in New World
      primates, Callitrichidae.
AB  - Measurement of immunoreactive progesterone, pregnanediol and oestradiol in faeces
      collected throughout ovarian cycles in three species of callitrichid primates is
      reported. Faecal hormone concentrations were compared with plasma progesterone
      profiles during PGF2 alpha-controlled (n = 7) and natural (n = 8) cycles in
      Callithrix jacchus and Saguinus fuscicollis, respectively, and with urinary
      oestrone conjugates during five cycles in Saguinus oedipus. Unconjugated
      steroids, which predominated over enzyme hydrolysable conjugates in samples from
      all species, were used to generate cycle profiles. According to results from
      HPLC, oestrone and oestradiol accounted for virtually all oestrogen
      immunoreactivity, and oestradiol most often predominated, whereas large amounts
      of nonspecific immunoreactivity were detected by both progesterone and
      pregnanediol assays. Faecal progestins were excreted in a cyclic manner in all
      species; luteal phase values were on average five- to tenfold higher than
      corresponding follicular phase values. Significant increases in mean amounts of
      faecal progestins were seen within 48 h of the post-ovulatory rise in plasma
      progesterone. Although a similar trend was also seen for faecal oestradiol, a
      clear and consistent luteal phase increase was seen only in Callithrix jacchus
      and this generally occurred later than that of progestins. The results indicate
      that faecal progestin analysis provides a useful method for noninvasive
      reproductive assessment in callitrichid primates. In particular, measurement of
      immunoreactive pregnanediol enables a multispecies application of a single assay
      methodology for comparative studies on callitrichid reproductive function.

PMID- 8283446
TI  - Association of ultrarapid freezing of mouse oocytes with increased polyploidy at
      the pronucleate stage, reduced cell numbers in blastocysts and impaired fetal
      development.
AB  - Mature mouse oocytes were frozen ultrarapidly with a cryoprotectant solution
      consisting of 3.5 mol dimethylsulfoxide l-1 and 0.5 mol sucrose l-1 or exposed to
      the freezing solution and recovered. Freshly collected oocytes were used as
      controls. After ultrarapid freezing and thawing, a high mean percentage of
      oocytes (78%) survived. The incidence of parthenogenetic activation in frozen
      thawed oocytes was not increased. After insemination in vitro, the rate of two
      cell formation was decreased (59% versus 69%). Examination of the chromosome
      complement of first-cleavage embryos revealed that the incidence of polyploid
      embryos was four times that of the control group (23% versus 6%). Fewer
      fertilized eggs progressed to the blastocyst stage (49% versus 81%) and the mean
      number of cells per blastocyst was decreased. Furthermore, the capacity of
      transferred blastocysts to develop in vivo was reduced. Autopsy at day 17 of
      gestation revealed that the proportion of embryos implanting was lower in the
      embryos derived from ultrarapidly frozen-thawed oocytes. Furthermore, some of the
      living fetuses were abnormal, but our sample size is too small for the effect to
      be significant. In the solution control group, no differences were found compared
      with the control group. Although the study needs further results to draw definite
      conclusions, our findings question whether the applied protocol is suitable for
      mouse oocytes.

PMID- 8283447
TI  - Secretion of immunoreactive beta-endorphin and GnRH by the pig uterus: effects of
      reproductive status and breed.
AB  - Immunoreactive beta-endorphin (ir-BEND) and GnRH (ir-GnRH) have been identified
      in the pig uterus. The study reported here examined (i) possible biochemical
      differences between ir-BEND and ir-GnRH present in pig uterine fluids and
      standard synthetic peptides, and (ii) the secretory profiles of uterine ir-BEND
      and ir-GnRH during the oestrous cycle and early pregnancy for two breeds of pig,
      Large White and the highly prolific Chinese Meishan. Reverse phase (RP)-HPLC
      analysis of concentrated uterine fluids indicated that the majority of ir-BEND
      eluted with a hydrophobicity similar to that of synthetic BEND 1-31 (BEND) and
      alpha-N-acetylated BEND 1-31 (Nac-BEND), with a ratio of BEND to Nac-BEND of
      approximately 1.8:1. The RP-HPLC profiles of ir-GnRH demonstrated a major peak
      coeluting with synthetic GnRH, along with a minor peak eluting at the void
      volume. Total content of ir-BEND (pg per uterus) was affected by the interaction
      of breed with day (P < 0.001), but was independent of reproductive status. In
      Large White gilts, uterine fluid content of ir-BEND was higher (P < 0.05) on days
      10 and 11 than on days 8, 12 and 14; however, in Meishan gilts, ir-BEND decreased
      from day 8 to days 10 and 11, and remained low on days 12 and 14. Compared to
      Meishan gilts, Large White gilts had higher ir-BEND concentrations on day 10 (P <
      0.01), day 11 (P < 0.0001), day 12 (P < 0.01) and day 14 (P < 0.02).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8283448
TI  - Activity of enzymes of energy metabolism in single human preimplantation embryos.
AB  - A method was developed to measure the activities of enzymes in extracts from
      single human preimplantation embryos. The method permits the analysis of two
      enzymes plus appropriate controls in an extract from a single embryo, and was
      used to investigate the control of energy metabolism during the development of
      human embryos from the two-cell to the blastocyst stage. Hexokinase (HK), 6
      phosphofructokinase (PFK), pyruvate kinase (PK), fructose-1,6-diphosphate
      aldolase (ALD), glucose phosphate isomerase (GPI), lactate dehydrogenase (LDH),
      glucose-6-phosphate dehydrogenase (G6PDH) and 2-oxoglutarate dehydrogenase (ODH)
      were all detectable, whereas glycogen phosphorylase (GP) was not. The enzyme
      activities of ODH, PFK, LDH, PK, GPI and G6PDH, averaged over all stages of
      development from the two-cell to blastocyst stage (days 2-6 after insemination),
      were 3.5, 6.6, 15, 69, 73 and 87 times greater than HK, respectively. The
      activity of ALD was very similar to that of HK. The activities of ALD, GPI, PFK,
      PK and LDH showed no significant variation with stage of development, although
      the activity of GPI fell significantly from the four-eight cell to the eight
      sixteen cell stage (P < 0.05). HK activity decreased from the two-eight cell to
      the eight-sixteen cell (P < 0.05), and increased significantly from the eight
      sixteen cell to the blastocyst stage (P < 0.01). The overall relationship between
      hexokinase activity and stage approached significance (P = 0.059, one-way
      analysis of variance). The activity of G6PDH decreased significantly with
      development (P < 0.001, one way analysis of variance).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8283449
TI  - DNA fingerprinting in relation to male dominance and paternity in a captive
      colony of tammar wallabies (Macropus eugenii).
AB  - The tammar wallaby has a polygynous mating system in which the dominant male
      usually controls initial access to oestrous females by mating first and then
      guarding the female from the advances of other subordinate males. In this study
      we used DNA fingerprinting with a human 3' hypervariable region (HVR) alpha
      globin probe to examine the paternity of pouch young progeny from 13 female
      tammars that were given continual access during the breeding season to a group of
      four sexually mature males. Constant individual-specific DNA profiles were
      observed for each animal. Paternity for 22 pouch young was successfully assigned
      using visual and computer-based analyses. However, no statistical difference was
      observed between the number of young sired by any of the four males (chi 2 = 2,
      d.f. = 3, P > 0.1). Mate guarding by the dominant male in our captive breeding
      group was not, therefore, sufficient to prevent successful subsequent matings by
      subordinates nor to enhance the genetic contribution of this male to the next
      generation. In each analysis, visual and computer assignments of paternity
      coincided, and these concurred with the results of a relatedness test which found
      that a large number of DNA bands were shared by sires and their progeny. The
      results from this paternity study show that first mating and subsequent mate
      guarding by the dominant male tammar wallaby in our captive group do not
      significantly skew the outcome of paternity towards this male and away from other
      males that subsequently mate with each female.

PMID- 8283450
TI  - Membrane and intracellular effects of ultraviolet irradiation with Hoechst 33342
      on bovine secondary oocytes matured in vitro.
AB  - Ultraviolet (UV) irradiation in combination with the bisbenzimide stain Hoechst
      33342 has been used to visualize the chromosomes before removal of oocytes to be
      used as cytoplasmic hosts for embryo nuclear transplantation. Short term effects
      of UV irradiation on the cytoplasmic viability of bovine oocytes matured in vitro
      were assessed by performing membrane and intracellular studies at 2 and 20 h
      after exposure to UV irradiation for 0, 30 or 60 s. At the membrane level, loss
      of integrity was shown by increased lysis and increased retention of the
      fluorescein diacetate dye in oocytes exposed to 60 s of UV irradiation and uptake
      of methionine was higher in both irradiated groups. At the intracellular level,
      methionine incorporation into protein was 5.8 times higher in controls than in
      oocytes exposed to UV irradiation for 60 s and there was a marked difference in
      the pattern of protein synthesis. Some changes in protein synthesis were also
      found in oocytes after 30 s exposure. Moreover, high levels of fluorescence with
      the dye rhodamine 123 at 20 h after exposure indicated large increases in
      mitochondrial membrane potential in both groups of UV-irradiated oocytes.
      Together, these findings indicate that exposure to UV irradiation for periods as
      short as 60 s causes alterations to both membrane and intracellular components of
      bovine oocytes matured in vitro. It is concluded that care must be taken when
      using this methodology to visualize or destroy metaphase chromosomes during
      enucleation in the embryo cloning protocol.

PMID- 8283451
TI  - Opioidergic regulation of gonadotrophin secretion in the early prepubertal bull
      calf.
AB  - The control of gonadotrophin secretion during the early developmental period in
      the bull is poorly understood; opioidergic regulation may be involved. The opioid
      antagonist naloxone was administered to bull calves (i.v. n = 5; 1 mg kg-1 body
      weight h-1) for 12 h at 4, 12, 18, 24 and 32 weeks of age. Control animals (n =
      5) received sterile saline solution. During the treatment period, 4 ml blood
      samples were collected every 12 min. The calves were also weighed and blood
      samples collected every two weeks from 2 to 48 weeks of age. Scrotal
      circumference was measured from 20 to 48 weeks of age to determine age at
      puberty. Serum samples were assayed for concentrations of LH, FSH, testosterone
      and oestradiol. On the basis of blood samples taken every two weeks, serum
      concentrations of LH increased to a peak at six weeks of age and then decreased;
      serum concentrations of FSH reached a peak at 20 weeks of age. Serum
      concentrations of testosterone and oestradiol increased with scrotal
      circumference from 20 to 48 weeks of age. On the basis of blood samples taken
      every 12 min for 12 h, we concluded that the early rise in serum LH
      concentrations was due to an increase in LH pulse frequency. LH pulse amplitude
      decreased from 4 to 18 weeks of age and FSH pulse amplitude from 4 to 32 weeks of
      age. Naloxone treatment increased LH pulse frequency at 4 and 24 weeks of age but
      not at 12, 18 or 32 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283452
TI  - Laparoscopic embryo transfer in rabbits.
AB  - A technique for endoscopic transfer of one-cell, one-two-cell, two-cell or morula
      stage embryos to the Fallopian tubes of rabbits was developed in two phases.
      Phase I of the experiments involved the transfer of 30-65 embryos to each of nine
      recipients and resulted in pregnancies in all animals. After 12 days six rabbits
      were killed and they showed an implantation rate of 27%. The remaining three
      rabbits continued pregnancy until birth. The embryo survival rate was 26%. In a
      second phase, 10-20 embryos were transferred to each of the 22 recipient animals,
      19 of which went on to give birth (embryo survival rate in the animals that
      became pregnant was 47%).

PMID- 8283453
TI  - Model of antral follicle dynamics during the 5-day cycle in rats based on
      measurement of antral follicle inflow.
AB  - Antral follicles were counted in ovaries from young adult Wistar rats, collected
      on the 5 days of the ovarian cycle. Follicles were classified as healthy, early
      atretic or late atretic and divided into five volume classes. From these data, a
      model was developed in which the inflow of healthy follicles into the various
      size classes was quantified. This model describes the follicle dynamics during a
      normal 5-day cycle. It was concluded that the stage of early atresia takes
      between 20 and 24 h. The inflow of follicles into the antral stage (volume > or =
      100 x 10(5) microns2) was continuous but not constant. The highest inflow was
      found during pro-oestrus and oestrus, at about the time of the first and second
      FSH surge. The total inflow during each cycle was about 120 follicles of which
      only 10% ovulated. These ovulating follicles were recruited during the previous
      pro-oestrus and oestrus. Follicle selection took place in volume classes 1 and 2
      (volume 100-350 x 10(5) microns3) during oestrus and dioestrus 1. At dioestrus 2,
      the follicles that will ovulate have been selected and can be recognized on the
      basis of their bigger size.

PMID- 8283454
TI  - Successful vitrification of day-6 sheep embryos.
AB  - The aim of the experiments described here was to investigate cryopreservation of
      day-6 sheep embryos by vitrification methods in which the preliminary procedures
      can be performed at room temperature using VS1 (5.5 mol ethylene glycol l-1 and
      2.5 mol glycerol l-1), VS11 (6.0 mol ethylene glycol l-1 and 1.8 mol glycerol l
      1) and VS14 (5.5 mol ethylene glycol l-1 and 1.0 mol sucrose l-1). None of the
      day-6 sheep embryos vitrified with VS1 survived. Day-6 sheep embryos with the
      exception of blastocysts were vitrified with VS11 with no loss of viability in
      vitro. The viability of transferred day-6 embryos vitrified with VS11 was however
      extremely poor. Osmotic damage was avoided by initially exposing the embryos to
      one of four dilutions (20%, 30%, 40% and 50%) of VS11 for 5 min at 25 degrees C
      and then vitrifying with the undiluted VS11. The highest survival (88.2%) in
      vitro was obtained when embryos were exposed to 30% VS11 before vitrification
      with the undiluted VS11. Survival of transferred embryos exposed to 30% VS11 and
      then vitrified with undiluted VS11 was 55% (16 of 29) for morulae and 62% (18 of
      29) for blastocysts. The pregnancy rate for recipients that received two
      vitrified sheep embryos of these developmental stages per ewe was 79% (22 of 28).
      In a small study performed with VS14 the survival of day-6 sheep embryos
      vitrified with VS14 (in one-step) was 100% in vitro and 50% after transfer.

PMID- 8283455
TI  - Endocrine changes and luteal morphology during pregnancy in muskoxen (Ovibos
      moschatus).
AB  - Progesterone, oestradiol and oestrone were measured in plasma from four captive
      muskoxen during three consecutive pregnancies (1983-1984, 1984-1985 and 1985
      1986). Jugular blood samples were collected weekly (1983) or on an alternating
      3:4 day schedule (1984-1986) during the first 12-15 weeks and last 6-10 weeks of
      pregnancy. Sampling during mid-pregnancy was at intervals of 2 weeks (1983 and
      1985) or 1 week (1986). Duration of gestation was about 34 weeks (235 +/- 4 (SD)
      days (n = 10), range 230-242 days). Progesterone remained at concentrations
      similar to those found during the luteal phase of the oestrous cycle for the
      first 10-12 weeks (mean +/- SEM 1.6 +/- 0.1 ng ml-1) after which it rose to a
      peak (mean 5.5 +/- 0.65 ng ml-1) between weeks 12 and 20. In all ten pregnancies
      progesterone concentrations declined dramatically between weeks 20 and 22 to
      luteal phase values where they remained until parturition. The decline was
      accompanied by an increase in oestradiol and oestrone concentrations which
      reached mean peak values of 199.23 +/- 87.23 pg ml-1 and 980.48 +/- 203.91 pg ml
      1, respectively. Corpora lutea collected from wild muskoxen between 45 and 80
      days gestation all showed histological evidence of regression, while corpora
      lutea from mid-gestation (112-125 days) were in advanced stages of involution.
      Repeated ovarian ultrasonography of captive muskoxen during the first 100 days of
      pregnancy confirmed these findings. The unusual, early regression of the corpus
      luteum of pregnancy indicates that progesterone and oestrogen of mid- and late
      pregnancy are probably of placental origin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283456
TI  - Production of normal young following transfer of mouse embryos obtained by in
      vitro fertilization between cryopreserved gametes.
AB  - Unfertilized oocytes (C57BL/6N and C3H/He) and epididymal spermatozoa (DBA/2N and
      Jcl:ICR) from mice were frozen separately and stored at -196 degrees C. After
      thawing, in vitro fertilization was performed using C57BL/6N oocytes and DBA/2N
      spermatozoa, C57BL/6N oocytes and Jcl:ICR spermatozoa, C3H/He oocytes and DBA/2N
      spermatozoa, and C3H/He oocytes and Jcl:ICR spermatozoa. Embryos developed to the
      two-cell stage by incubation in vitro were transferred to the oviducts of female
      recipients on the first day of pseudopregnancy (day when vaginal plug was
      confirmed). The rate of development to two-cell embryos in each group was in the
      22-45% range. When these two-cell embryos were all transferred to recipients,
      offspring were produced from 23-35% of the embryos.

PMID- 8283457
TI  - LH responses to single doses of exogenous GnRH by freshly captured Damaraland
      mole-rats, Cryptomys damarensis.
AB  - Pituitary function in reproductive and nonreproductive colony members of
      Damaraland mole-rats, Cryptomys damarensis, was investigated by measuring the LH
      responses to single doses of 2 micrograms exogenous GnRH and physiological saline
      in 29 females and 37 males (31 of these animals from two entire colonies). In
      females, basal LH concentrations were significantly greater in reproductive (n =
      9) than in nonreproductive animals (n = 11): 7.6 +/- 1.0 versus 4.3 +/- 0.6 miu
      ml-1, respectively (P < 0.001). Reproductive females had a significantly greater
      LH response to 2.0 micrograms GnRH (7.6 +/- 1.0 to 37.7 +/- 6.2 miu ml-1; n = 9)
      than did nonreproductive females (4.3 +/- 0.6 to 11.8 +/- 1.0 miu ml-1; n = 11, P
      < 0.001). In contrast, there was no significant difference in basal LH
      concentrations between reproductive (n = 8) and nonreproductive males (n = 20):
      5.3 +/- 4.3 versus 3.2 +/- 1.2 miu ml-1, respectively. There was also no
      difference in LH response to the administration of 2.0 micrograms GnRH between
      reproductive and nonreproductive males (5.3 +/- 4.3 to 21.8 +/- 8.6 miu ml-1; n =
      8; versus 3.2 +/- 1.2 to 21.1 +/- 8.5 miu ml-1; n = 21; P = 0.5). When the
      results from the two entire colonies were analysed separately, LH responses to
      GnRH in the 11 nonreproductive females were less than in the two reproductive
      females. In contrast, the response of two reproductive males in the colonies did
      not differ from that of 16 nonreproductive males, although these latter
      comparisons could not be validated statistically.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8283458
TI  - Effects of pyruvate and glucose on the development of human preimplantation
      embryos in vitro.
AB  - Although human embryos will develop in vitro for six days or more, little is
      known about the effects of the primary nutrients, pyruvate and glucose, on
      development. Because the nutrient requirements of embryos change throughout
      preimplantation development, the effects of altering substrate concentrations in
      the culture medium were examined, using 'surplus' human preimplantation embryos
      cultured from the two-four-cell stage to the blastocyst stage in medium
      containing various concentrations of pyruvate and glucose. Between the one-cell
      stage and the two-four-cell stage all of the embryos were exposed to 0.47 mmol
      pyruvate l-1 and 5.5 mmol glucose l-1. Pyruvate as sole substrate in the medium
      could support blastocyst development to an extent of 59% (10 of 17). Conversely,
      culture of embryos in pyruvate-free medium resulted in the developmental arrest
      of 84% (21 of 25) of embryos, and for the 16% (4 of 25) that did reach the
      blastocyst stage there was a significant decrease in metabolic activity on day 4
      5, during the morula to blastocyst stage transition. Embryos could not use
      glucose to compensate for the lack of pyruvate in the medium. Pyruvate uptake was
      related to exogenous concentration and optimal development occurred at the
      highest concentration tested, 0.47 mmol l-1. Embryo development to the eight-cell
      stage was slightly enhanced 82% (14 of 17) versus 60% (24 of 40) when no glucose
      was added to the medium, and the resulting blastocysts had significantly more
      cells (99.1 +/- 13.5 versus 58.4 +/- 8.2; P < 0.02) than did embryos grown in the
      presence of 1 mmol glucose l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283459
TI  - Effects of follicular fluid at fertilization in vitro on sperm penetration in pig
      oocytes.
AB  - The effects of porcine follicular fluid (PFF) on sperm penetration of pig oocytes
      and on prevention of polyspermy were examined and characteristics of spermatozoa
      exposed to PFF were determined. The addition of PFF at the level of 1 and 10% to
      the prefertilization and fertilization media decreased penetration rates and the
      mean number of spermatozoa in penetrated eggs regardless of the origin of PFF. In
      the presence of BSA, supplementation of 0.1% PFF to prefertilization and
      fertilization media and 1% PFF to prefertilization media did not decrease the
      penetration rates but did increase monospermic penetration to 54 and 68%,
      respectively. When PFF was added to prefertilization media, the number of
      spermatozoa binding to the zona and the percentage of acrosome-intact spermatozoa
      decreased with increased PFF concentration (from 43.1 +/- 2.8 and 73.1 +/- 4.9%
      to 7.2 +/- 1.3 and 15.7 +/- 15.4%, respectively). At the end of prefertilization
      incubation, sperm agglutination was observed and the degree depended on PFF
      concentration. Supplementation of fetal calf serum to prefertilization and
      fertilization media blocked the effects of PFF on sperm penetration and binding
      of spermatozoa to the zona. These results indicate that the prefertilization
      incubation of porcine spermatozoa in suitable concentrations of porcine
      follicular fluid will effectively reduce both the number of spermatozoa that
      attach to the surface of pig eggs and the incidence of polyspermy.

PMID- 8283460
TI  - Society for the Study of Fertility and German Society for the Study of Fertility
      and Sterility, Winter meeting. Aachen, December 1993. Abstracts.

PMID- 8283461
TI  - Laparoscopic inguinal herniorrhaphy: initial experience in a community hospital.
AB  - Since February 1992, 32 laparoscopic herniorrhaphies have been performed in 25
      patients, including 15 indirect, 16 direct and 1 femoral defect. These were
      performed in a 275 bed community hospital initially using a "plug and patch"
      technique, and later employing repair of the hernia defect with a sheet of
      prolene mesh only. Patients were managed on an out patient basis and were able to
      resume full activity in 7 to 10 days. Despite the lack of long term follow-up and
      additional cost basis for the laparoscopic procedures, this method of repairing
      hernia defects promises to be safe and effective with a high degree of patient
      satisfaction.

PMID- 8283462
TI  - Physicochemical stress in the production of disease.

PMID- 8283463
TI  - The new PRO.

PMID- 8283464
TI  - Ensuring quality under national health care reform.

PMID- 8283465
TI  - Post-ischemic contractile dysfunction does not correlate with an elevated
      intracellular free [Mg2+]: a 31P-NMR study on isolated rat and rabbit hearts.
AB  - The aim of this study was to investigate whether intracellular free Mg2+ (Mgr),
      which increases during myocardial ischemia due to hydrolysis of ATP, remained
      elevated during reperfusion after a relatively short period of ischemia and
      thereby could account for temporary post-ischemic contractile dysfunction, often
      referred to as stunning. 31P-magnetic resonance (31P-NMR) spectroscopy was used
      to follow creatine phosphate, adenosine triphosphate, intracellular inorganic
      phosphate, intracellular pH and Mgr simultaneously with left ventricular
      developed pressure (LVDP) and coronary flow in isolated rat and rabbit hearts,
      which were perfused (37 degrees C) according to Langndorff. LVDP was measured in
      an isovolumic way by means of an intraventricular latex balloon. Rat hearts (300
      beats/min) were made globally ischemic for 15 min and rabbit hearts (180
      beats/min) for 15 or 20 min. All hearts were reperfused for 60 min. Control
      hearts were perfused for 75 min without being made ischemic. During ischemia Mgr
      (mmol/l) increased from 0.76 +/- 0.20 to 4.34 +2- 1.99 in the rat hearts, and
      from 0.72 +/- 0.22 to 2.18 +/- 1.06 (15 min) and 2.35 +/- 1.26 (20 min) in the
      rabbit hearts. During reperfusion Mgr in the three groups returned to the level
      of the control hearts within 7.5 min, and LVDP within 25 min. At the end of the
      reperfusion period ATP content amounted to 56 +/- 17% (rat hearts), 66 +/- 10%
      (rabbit hearts; 15 min ischemia group) and 61 +/- 7% (rabbit hearts; 20 min
      ischemia group) of the pre-ischemic levels. The results confirm that in vitro
      stunning is a short-lived phenomenon and indicate that an increased Mgr is not
      involved in this temporary mechanical dysfunction.

PMID- 8283466
TI  - Effects of age on c-fos and c-myc gene expression in response to hemodynamic
      stress in isolated, perfused rat hearts.
AB  - Using an ex vivo model we examined whether the age-associated modulation of proto
      oncogene expression was due to the aging of the heart per se. In the two age
      groups of Wistar rats (2 and 18 months), expression of c-fos and c-myc genes was
      determined in isolated, isovolumically contracting hearts (balloon in the left
      ventricle) perfused with Tyrode's solution containing bovine serum and red blood
      cells. In both age groups, a c-fos signal was detected at 30 min, increased
      further at 60 min, and declined at 120 min, while the c-myc signal was detected
      at 60 min and increased for a further 120 min after initiation of perfusion at 25
      mmHg of end-diastolic pressure (EDP). The expression of these genes by 60 min of
      relatively mild hemodynamic stress was depressed in old hearts compared to that
      in young hearts (c-fos at 0 (P < 0.05), 5 (P < 0.05) and 15 mmHg of EDP (P <
      0.01); c-myc at 5 (P < 0.05) and 15 mmHg (P < 0.05)). The age-associated
      differences in the expression of these genes were smaller under severe
      hemodynamic stress (25 mmHg of EDP). Peak systolic and diastolic wall stress
      calculated from left ventricular pressure, cavity volume and muscle weight were
      similar in the two age groups. Thus, aging diminishes the expression of proto
      oncogenes and seems to elevate the threshold at which hemodynamic stress to the
      heart results in a response at the gene level. The age-associated modulation is
      caused by aging of the heart per se.

PMID- 8283467
TI  - Norepinephrine in neonatal rat ventricular myocytes: association with the cell
      nucleus and binding to nuclear alpha 1- and beta-adrenergic receptors.
AB  - Chronic exposure of neonatal rat ventricular myocytes to norepinephrine (NE) has
      been demonstrated to induce fetal cardiac gene expression and hypertrophy. The
      precise signaling mechanism of NE induction, as well as the long delay for the
      onset of NE effect, are not well understood. To examine the possibility that the
      hormone may be transported into the cell and exerts its effect through an
      intracellular site, ventricular myocytes from neonatal rats were incubated with
      [3H]-labeled NE and the cytosolic and nuclear fractions of the cell were measured
      for radioactivity. The presence of intracellular adrenergic binding sites was
      also explored. Following incubation of neonatal rat ventricular myocytes with
      [3H]NE for different time intervals (from 30 min to 22 h), the highest proportion
      (more than 80%) of NE taken up by the cell was recovered in the nuclear fraction.
      The nuclear accumulation was slow and time-dependent, being non-detectable in the
      first 60 min. Furthermore, isolated nuclei from the ventricular myocytes contain
      binding sites for [3H]prazosin and dihydroalprenolol, suggesting the presence of
      alpha 1 and beta 1 adrenergic receptors. The apparent KD and Bmax were 0.6 nM and
      0.6 fmol/mg protein for alpha 1-adrenergic receptors, while beta-adrenergic
      nuclear receptors exhibited an apparent KD of 12 nM and a Bmax of 61 fmol/mg
      protein. Thus, neonatal rat ventricular myocytes exposed to NE accumulate the
      hormone in the cell nucleus where it can bind to high affinity alpha 1- and beta
      adrenergic receptors.

PMID- 8283468
TI  - Paradoxical twitch potentiation after rest in cardiac muscle: increased
      fractional release of SR calcium.
AB  - Rest interval dependent changes in contractile force (rest decay and rest
      potentiation) were studied in rabbit, rat and ferret ventricular muscle and
      myocytes. The SR Ca content was assessed by rapid cooling contractures or
      caffeine induced contractures. Intracellular Ca transients, action potentials and
      Ca current were also recorded. Rest decay of twitches in rabbit ventricle are
      roughly paralleled by a decline in SR Ca content. Rat ventricle exhibits
      primarily rest potentiation, which is not necessarily paralleled by an increased
      SR Ca content. Ferret ventricle exhibits both rest potentiation and rest decay.
      However, the SR Ca content in ferret appears to decline monotonically throughout
      the rest. It is demonstrated that the rest potentiation is not due to an increase
      in Ca current or in action potential duration. We conclude that there is an
      increase in the fraction of SR Ca content which is released during the time that
      rest potentiation develops. The differences in post-rest contractile function
      among different cardiac preparations can be described by a simple unifying
      mechanistic model. In this model there is an exponential time dependent recovery
      of the ability of the SR to release Ca (e.g. recovery from inactivation) which
      can be considered to increase the fraction of SR Ca release in response to
      activation. This fractional SR Ca release is multiplied by the SR Ca content
      (which may decline exponentially) to provide a measure of the Ca available for
      activation of contractile force.

PMID- 8283469
TI  - R 56865 delays cellular electrical uncoupling in ischemic rabbit papillary
      muscle.
AB  - The compound R56865 protects the heart from irreversible ischemic damage. The
      proposed mechanism of its action is a reduction of Ca2+ overload secondary to a
      reduction of intracellular Na+, caused by blockade of the Na(+)-channel. In
      addition, cardioprotection is ascribed to blockade of the Na(+)-sensitive K(+)
      channel (IK-Na). We tested whether R 56865 delays cellular electrical uncoupling,
      one aspect of irreversible ischemic damage that is due to Ca2+ overload. Also, we
      studied whether the Na(+)-channel and IK-Na are involved in cardioprotection by
      relating delay of the onset of cellular electrical uncoupling to changes of
      conduction velocity and action potential duration (APD80), respectively.
      Experiments were performed with isolated perfused rabbit papillary muscles that
      were treated with 1 microM R 56865 for 45 min prior to ischemia. Uncoupling
      started at 15.0 +/- 0.8 min (mean +/- S.E.M., n = 12) of ischemia in the control
      group and at 23.4 +/- 1.7 min in the R 56865 group (n = 9, P < 0.005 vs control).
      R 56865 tended to decrease conduction velocity and to increase APD80 during pre
      treatment, but these changes were not statistically significant. During ischemia,
      conduction velocity was statistically not different between the R 56865 group and
      the control group. APD80 was significantly longer in the R 56865 than in the
      control group during the first 7 min of ischemia and similar after that. We
      conclude that R 56865 delays the onset of cellular uncoupling during ischemia and
      that this effect is not related to changes of conduction velocity and at most in
      part to changes of APD80.

PMID- 8283470
TI  - Effect of alpha-tocopherol on high energy phosphate metabolite levels in rat
      heart by 31P-NMR using a Langendorff perfusion technique.
AB  - To examine the action of alpha-tocopherol on high energy phosphate compounds, a
      31P-NMR technique was applied to perfused Langendorff rat hearts. Rats were
      treated with tocopherol acetate (25 mg/kg body wt i.p.) for 7 consecutive days.
      On the 7th day, the rat hearts were isolated for the Langendorff experiment.
      After 30 min of global ischemia the NMR signals of creatine phosphate and ATP in
      myocardium disappeared, and then recovered slightly in the reperfusion following
      ischemia. However, in the tocopherol-treated rat hearts, the restoration of high
      energy phosphate compounds occurred quickly after the beginning of reperfusion,
      although there was no significant difference in the destruction of high energy
      phosphate compounds during the ischemia. The alpha-tocopherol level in the
      myocardium was severely depleted by ischemia-reperfusion. In the alpha-tocopherol
      treated animals, the alpha-tocopherol level in myocardium was still significantly
      higher than the control level at the end of 30 min of global ischemia. The heart
      mitochondrial respiratory function was simultaneously protected against ischemia
      reperfusion injury. The role of alpha-tocopherol was discussed as a radical
      scavenger and membrane stabilizer against oxygen stress.

PMID- 8283471
TI  - Phospholipase inhibition and the electrophysiology of acute ischemia: studies
      with amiodarone.
AB  - Previous studies have shown a close temporal relationship between lipid
      abnormalities and membrane dysfunction in ischemia and that phospholipase
      inhibiting drugs limit such derangements. Amiodarone is a potent phospholipase
      inhibitor, but its potential or that of any other inhibitor to simultaneously
      attenuate lipid abnormalities and electrophysiological changes in the very early
      phase of ischemia has never been studied. We therefore investigated
      simultaneously such changes in early ischemia. In isolated porcine hearts
      perfused with or without pure amiodarone solutions, electrophysiologic changes
      before and during 20 min of LAD occlusion were recorded using unipolar electrodes
      and Franz contact electrode catheters, and full thickness myocardial biopsies
      obtained for lipid analyses. In untreated hearts (n = 5), occlusion of LAD
      resulted in the rapid onset of TQ depression/ST elevation within 1 min and
      plateauing at 10 min. There were mean increases of 33% and 50% in
      lysophosphatidylcholine and 33% and 70% in lysophosphatidylethanolamine levels at
      5-7 min and 20 min of ischemia, respectively. Non-esterified fatty acid (NEFA)
      content did not change significantly during the first 5-7 min, but increased by
      75% after 20 min of LAD occlusion. In treated hearts (n = 5) there was a 37%
      increase in sinus cycle length after amiodarone administration (503 +/- 85 vs 689
      +/- 115 ms, P < 0.01) but no significant change in ventricular effective
      refractory period (202 +/- 22 vs 204 +/- 21 ms), action potential duration (215
      +/- 11 vs 217 +/- 7 ms), or amplitude (31 +/- 6 vs 28 +/- 3 mV) was observed.
      Also, amiodarone treatment did not alter total phospholipid content,
      lysophospholipids and NEFA levels of non-ischemic hearts. However, there was
      significant attenuation (P < 0.01) of the onset of the TQ/ST shift and
      preservation of action potential amplitude (P < 0.02) during the first 5-7 min of
      LAD occlusion with concomitant suppression of the increase in both
      lysophospholipids (hydrolysis products of membrane phospholipids by endogenous
      phospholipases) and NEFA levels observed after 5-7 and 20 min of ischemia. The
      results suggest that amiodarone can delay the onset and limit the extent of
      electrophysiologic change in early myocardial ischemia in temporal association
      with suppression of myocardial phospholipase activities.

PMID- 8283472
TI  - Quantitative reduction of MTT by hearts biopsies in vitro is an index of
      viability.
AB  - The aim of this study is to evaluate the use of tetrazolium reductase (TR)
      activity as an indicator of myocardial viability in an isolated arrested pig
      heart biopsy model. Methyl Tetrazolium (MTT) is cleaved by an enzyme in the
      presence of coenzymes NAD, NADP. Cleavage yields a highly colored formazan
      product which is DMSO soluble. Efficient bioreduction of MTT has been
      investigated with heart biopsies. The relationship between MTT reduction and (1)
      oxygen consumption (r = 0.96, P < 0.001), (2) the sum of the adenine nucleotide
      levels (r = 0.87, P < 0.001) and (3) localization of coloration, has been
      established. The use of MTT in colorimetric assays offers high sensitivity. MTT
      reduction is a valid method. It is rapid and reproducible, and can be used as an
      indicator of myocardial viability. The MTT test has been used to rapidly compare
      the effect of different cardioplegic solutions (St Thomas and improved St Thomas)
      on hypothermic cardiac preservation. Significant differences have been
      established between the two solutions (P < 0.01).

PMID- 8283473
TI  - Effects of thiol protease inhibitors on fodrin degradation during hypoxia in
      cultured myocytes.
AB  - The effects of thiol protease inhibitors on fodrin (a cell membrane nonerythroid
      spectrum-like protein) degradation were studied during hypoxia in cultured
      myocytes. Cardiac myocytes, isolated from neonatal rat hearts, were incubated
      under hypoxic conditions for 6 h. Cell membrane proteins, including fodrin,
      prepared from hypoxic myocytes were examined with electroblots stained for fodrin
      by the peroxidase method. Cell death during hypoxia rose to 80% after 6 h.
      Intracellular protease activity was also elevated in hypoxia. This intracellular
      protease activity was markedly inhibited by the cysteine protease inhibitor E-64
      and calpain inhibitor 1. Hypoxic cell death was also suppressed by E-64 and
      calpain inhibitor 1. A 125 kDa immunoreactive degradation product of fodrin was
      found in hypoxic conditions. Treatment with E-64 and calpain inhibitor 1
      decreased both the appearance of this band and the degradation of fodrin. These
      observations indicate that intracellular thiol proteases, including calpains, are
      activated during hypoxia and that these are related to cell membrane protein
      degradation, especially of fodrin. The data also suggest that protease inhibitor
      E-64 treatment may be beneficial in protection against hypoxic myocyte injury.

PMID- 8283474
TI  - Glycyl-L-glutamine regulates the expression of asymmetric acetylcholinesterase
      molecular forms in cultured cardiac post-natal myocytes.
AB  - Asymmetric acetylcholinesterase (AChE) forms were associated with pre-natal but
      not post-natal ventricular myocytes, when myocytes were cultured in a defined
      medium on laminin-coated plates for 72 h. In contrast, globular AChE molecular
      forms were associated with both pre-natal and post-natal myocytes. Glycyl-L
      glutamine (10(-4) or 109-6) M), but not glycyl-D-glutamine or glycyl-L-glutamate,
      induced the expression of asymmetric AChE molecular forms by the cultured post
      natal myocytes. Neither of the three dipeptides altered the specific activity of
      cell-associated AChE in the cultured post-natal ventricular myocytes. Tetrameric
      globular (G4) AChE was the main AChE form secreted by cultured pre-natal and post
      natal cardiac myocytes. The secretion rate of AChE from post-natal myocytes was
      not affected by the addition of glycyl-L-glutamine. These results suggest that
      glycyl-L-glutamine has a trophic effect on at least one of the components of the
      post-synaptic cholinergic system in developing rat heart.

PMID- 8283475
TI  - Attenuation by heat stress of a submaximal calcium paradox in the rabbit heart.
AB  - Heat stress limits the injury associated with myocardial ischaemia and
      reperfusion, an effect previously attributed to enhanced endogenous anti-oxidant
      activity. We examined the influence of heat stress on the calcium paradox, an
      injury in which oxidant stress is not thought to play a major role. Twenty-four
      hours following sham or true heat stress, rabbits were re-anaesthetized and
      hearts either removed for stress protein analysis (n = 8), or Langendorff
      perfused (n = 20) and subjected to a calcium paradox. Ten minutes following
      calcium repletion (Ca2+ = 1.3 mM), left ventricular developed pressure was better
      preserved in heat stress vs control hearts (38.3 +/- 5.0 vs 18.8 +/- 4.1 mmHg,
      respectively, P = 0.003) whilst contracture, measured by left ventricular end
      diastolic pressure, was diminished (21.6 +/- 4.7 vs 39.9 +/- 5.2 mmHg,
      respectively, P = 0.02). Creatine phosphokinase release at 1 min was less in heat
      stress vs control hearts (10.6 +/- 8.6 vs 86.4 +/- 33.7 U/min/g, respectively, P
      = 0.01). The myocardial content of the 72 kDa stress protein was elevated eight
      fold in heat stress vs control hearts (2.8 +/- 0.2 vs 0.4 +/- 0.1 U,
      respectively, P = 0.01). This study suggests that some portion of the stress
      protein response represents a form of cardiac adaptation capable of limiting
      myocyte injury independent of antioxidant mechanisms.

PMID- 8283476
TI  - Regional energy metabolism of failing hearts following myocardial infarction.
AB  - To elucidate the relationship between functional alterations and disturbances in
      myocardial energy metabolism of rats with heart failure following coronary artery
      ligation, the left coronary artery of the rat was ligated and the time course of
      changes in cardiac function and myocardial energy state of the animal were
      examined for 12 weeks after the ligation. Coronary artery ligation resulted in
      approximately 40% infarction of the left ventricle, an increase in the right
      ventricular weight, a decrease in left ventricular developed pressure, an
      increase in left ventricular end-diastolic pressure throughout the experiment,
      suggesting the development of cardiac failure after the operation. Cardiac output
      and stroke volume indices were not altered during the first 4 weeks, but were
      significantly decreased on the 8th and 12th weeks, suggesting that cardiac
      function had further aggravated by 8 weeks after the operation. Myocardial energy
      profiles of the scar tissue, the remaining left ventricle and interseptum, and
      the right ventricle were determined. Tissue ATP (27.54 +/- 0.82 to 26.38 +/- 1.58
      mumol/g dry tissue; n = 8-10) and creatine phosphate (26.73 +/- 1.63 to 24.38 +/-
      1.83 mumol/g dry tissue; n = 8-10) of the remaining viable left ventricle were
      lower than control (33.17 +/- 0.73 and 40.04 +/- 1.07 mumol/g dry tissue; n = 8)
      throughout the experiment. A marked decrease in tissue ATP and CP was seen in the
      scar tissue throughout the experiment. Increases in tissue lactate of the
      remaining left ventricle and the right ventricle were detected from 1 to 2 weeks
      after the operation, but returned to the control levels thereafter. Mitochondrial
      oxygen consumption rates of isolated myocardial bundles from the 8th and 12th
      weeks (21.03 +/- 2.22 and 17.79 +/- 3.24 ng oxygen/min/mg dry tissue; n = 8) were
      lower than control (33.15 +/- 1.95 ng oxygen/min/mg dry tissue; n = 5), and those
      of the interseptum (23.71 +/- 1.33 ng oxygen/min/mg dry tissue; n = 8) and the
      right ventricle (22.44 +/- 2.73 ng oxygen/min/mg dry tissue; n = 8) on the 12th
      week after the operation were lower than control (33.58 +/- 2.80 and 34.83 +/-
      2.64 ng oxygen/min/mg dry tissue; n = 5). The results provide evidence for a
      decline in myocardial energy store and energy producing ability associated with
      the development of cardiac failure.

PMID- 8283477
TI  - A new member of the balbiani ring multigene family in the dipteran Chironomus
      tentans consists of a single-copy version of a unit repeated in other gene family
      members.
AB  - The known Balbiani ring (BR) multigene family members in the dipteran Chironomus
      tentans encode salivary gland secretory proteins in the size range between 38 and
      1,000 kDa. The proteins interact to form protein fibers used by the aquatic
      larvae to spin feeding and protective larval tubes or pupation tubes. Here, we
      describe a new BR multigene family member, the sp17 gene, which codes for an 89
      amino-acid-long protein with a relative mobility of 17k. The gene has a high
      content of charged amino acid residues and consists of two structurally different
      halves. Five regularly spaced cysteine codons are present in the 5' half while
      the 3' half contains five proline codons. These two different halves exhibit
      similarities to the C and SR regions, respectively, which form the tandemly
      repeated units in the about 40-kb-long BR genes and which also, in different
      versions, are the building blocks of all genes in the BR multigene family. In
      this multigene family, encoding interacting structural proteins, the long BR
      genes with their 125-150 tandemly arranged repeat units as well as the short sp17
      gene with its single-copy version of such a repeat unit, have therefore evolved
      from a common ancestor.

PMID- 8283478
TI  - Organization and evolution of an alpha satellite DNA subset shared by human
      chromosomes 13 and 21.
AB  - The structure of the alpha satellite DNA higher-order repeat (HOR) unit from a
      subset shared by human chromosomes 13 and 21 (D13Z1 and D21Z1) has been examined
      in detail. By using a panel of hybrids possessing either a chromosome 13 or a
      chromosome 21, different HOR unit genotypes on chromosomes 13 and 21 have been
      distinguished. We have also determined the basis for a variant HOR unit structure
      found on approximately 8% of chromosomes 13 but not at all on chromosomes 21.
      Genomic restriction maps of the HOR units found on the two chromosome 13
      genotypes and on the chromosome 21 genotype are constructed and compared. The
      nucleotide sequence of a predominant 1.9-kilobasepair HOR unit from the
      D13Z1/D21Z1 subset has been determined. The DNA sequences of different alpha
      satellite monomers comprising the HOR are compared, and the data are used to
      develop a model, based on unequal crossing-over, for the evolution of the current
      HOR unit found at the centromeres of both these chromosomes.

PMID- 8283479
TI  - Phylogenetic relationships of ferns deduced from rbcL gene sequence.
AB  - Part of the large subunit of the ribulose-1,5-bisphosphate carboxylase/oxygenase
      (rubisco) gene (rbcL) was sequenced from three fern species: Adiantum capillus
      veneris, Botrypus strictus, and Osmunda cinnamomea var. fokiensis. This region
      included 1,333 base pairs, about 90% of the gene. Maximum likelihood analysis of
      the deduced amino acid sequences indicated that (1) Botrypus (Ophioglossaceae)
      clustered monophyletically with other ferns (Adiantum, Angiopteris, Osmunda); the
      closest relative to Botrypus among the three species was Osmunda, which did not
      support the hypothesis that the Ophioglossaceae are linked to the progymnosperm
      seed plant lineage. (2) Eusporangiate ferns containing Botrypus (Ophioglossaceae)
      and Angiopteris (Marattiaceae) were a paraphyletic group. (3) Seed plants and the
      four fern species examined formed a monophyletic group, but ferns and bryophytes
      (liverwort) did not. Variations in rates of substitution for synonymous and
      nonsynonymous codons were found in fern lineages.

PMID- 8283480
TI  - Homopolymer length variation in the Drosophila gene mastermind.
AB  - Runs of identical amino acids encoded by triplet repeats (homopolymers) are
      components of numerous proteins, yet their role is poorly understood. Large
      numbers of homopolymers are present in the Drosophila melanogaster mastermind
      (mam) protein surrounding several unique charged amino acid clusters. Comparison
      of mam sequences from D. virilis and D. melanogaster reveals a high level of
      amino acid conservation in the charged clusters. In contrast, significant
      divergence is found in repetitive regions resulting from numerous amino acid
      replacements and large insertions and deletions. It appears that repetitive
      regions are under less selective pressure than unique regions, consistent with
      the idea that homopolymers act as flexible spacers separating functional domains
      in proteins. Notwithstanding extensive length variation in intervening
      homopolymers, there is extreme conservation of the amino acid spacing of specific
      charge clusters. The results support a model where homopolymer length variability
      is constrained by natural selection.

PMID- 8283481
TI  - Two subfamilies of MDG1 retrotransposon with different evolutionary histories in
      D. melanogaster.
AB  - Two copies of nonmobile retrotransposon localized in D. melanogaster
      heterochromatin (mdg1het) were sequenced at the 3'-end. The comparison of 2.5-kb
      mdg1het sequences with the sequence of cognate euchomatic transposable copies
      (mdg1tr) revealed an intact mdg1 ORF2 encoding the pol gene in mdg1het, and two
      thirds of nucleotide substitutions in this ORF were synonymous. All the known
      mdg1 regulatory elements in the mdg1het LTR also are conserved, in spite of
      numerous deletions and nucleotide substitutions elsewhere in this region. These
      data suggest that the mdg1het subfamily lost its mobility more recently than
      other functions were lost. The G-->A hypermutation known to occur in the reverse
      transcription cycle of retroviruses was detected in one mdg1het copy. The
      structure of the enchancer-like region in mdg1het suggests a reduced
      transcription level and, therefore, transposition frequency, relative to mdg1tr.
      The number of nucleotide substitutions suggests that the time of mdg1het mobility
      loss was less than 0.3-0.5 Myr ago.

PMID- 8283482
TI  - Molecular phylogeny of Drosophila based on ribosomal RNA sequences.
AB  - Nucleotide sequences of 72 species of Drosophilidae were determined for divergent
      D1 and D2 domains (representing 200 and 341 nucleotides respectively in D.
      melanogaster) of large ribosomal RNA, using the rRNA direct sequencing method.
      Molecular phylogenetic trees were reconstructed using both distance and parsimony
      methods and the robustness of the nodes was evaluated by the bootstrap procedure.
      The trees obtained by these methods revealed four main lineages or clades which
      do not correspond to the taxonomical hierarchy. In our results, the genus
      Chymomyza is associated with the subgenus Scaptodrosophila of the genus
      Drosophila and their cluster constitutes the most ancient clade. The two other
      clades are constituted of groups belonging to the subgenus Sophophora of the
      genus Drosophila: the so-called Neotropical clade including the willistoni and
      saltans groups and the obscura-melanogaster clade itself split into three
      lineages: (1) obscura group + ananassae subgroup, (2) montium subgroup, and (3)
      melanogaster + Oriental subgroups. The fourth clade, the Drosophila one, contains
      three lineages. D. polychaeta, D. iri, and D. fraburu are branched together and
      constitute the most ancient lineage; the second lineage includes the annulimana,
      bromeliae, dreyfusi, melanica, mesophragmatica, repleta, robusta, and virilis
      groups. The third lineage is composed of the immigrans and the cardini, funebris,
      guaramunu, guarani, histrio, pallidipennis, quinaria, and tripunctata groups. The
      genera Samoaia, Scaptomyza, and Zaprionus are branched within the Drosophila
      clade. Although these four clades appear regularly in almost all tree
      calculations, additional sequencing will be necessary to determine their precise
      relationships.

PMID- 8283483
TI  - Preventing colon cancer: yet another reason not to smoke.

PMID- 8283484
TI  - Hair dye and cancer: reassuring evidence of no association.

PMID- 8283485
TI  - Aspirin's next conquest: does it prevent colon cancer?

PMID- 8283486
TI  - Linked databases help researchers track costs, care patterns, outcomes.

PMID- 8283487
TI  - ISO research M.D.s: clinical scientists needed for biomedical boom.

PMID- 8283488
TI  - Anti-cancer drug origins: truth is stranger than fiction.

PMID- 8283489
TI  - Researchers test TIMP-2 as potential tumor terminator.

PMID- 8283490
TI  - A prospective study of cigarette smoking and risk of colorectal adenoma and
      colorectal cancer in U.S. men.
AB  - BACKGROUND: Epidemiologic studies of men consistently demonstrate a positive
      association between tobacco smoking and risk of colorectal adenomas, precursors
      of cancer, but have not consistently shown an association between smoking and
      colorectal cancer. We hypothesized that smoking acts as an initiator of
      colorectal neoplasia and that the association with cancer has been obscured
      because the time is long between onset of smoking and diagnosis of cancer.
      PURPOSE: Our purpose was to examine the association between cigarette smoking and
      risk of colorectal adenoma and colorectal cancer in men and to estimate the
      minimum induction period between the start of smoking and the diagnosis of
      cancer. METHODS: Using data from the ongoing Health Professionals Follow-up
      Study, we assessed the relative risk (RR) of small adenoma, large adenoma (> or =
      1 cm), and cancer according to pack-years of smoking. Current and lifetime
      histories of smoking and other confounding factors were assessed by questionnaire
      at baseline and at 2-year intervals. Between 1986 and 1992, we documented 238 new
      cases of colorectal cancer among 47,935 U.S. males and 626 new cases of
      colorectal adenomas among 12,854 of the men who had a sigmoidoscopy or
      colonoscopy. RESULTS: Smoking during the prior two decades was associated with
      the prevalence of small adenomas (RR = 2.96; 95% confidence interval [CI] = 1.47
      5.98; for > or = 35 pack-years versus 0 pack-years within the 20 years preceding
      the endoscopy, P trend = .04) but not with large adenomas (RR = 0.46; 95% CI =
      0.11-1.94; P trend = .56). However, smoking more than 20 years in the past was
      associated with large adenomas (RR = 2.38; 95% CI = 1.56-3.63; P trend = .004 for
      smoking > or = 16 pack-years versus 0 pack-years). Smoking was related to risk of
      colorectal cancer only after allowing for an induction period of at least 35
      years (RR = 1.94; 95% CI = 1.13-3.35; P trend = .008 for smoking > or = 16 versus
      0 pack-years more than 35 years in the past). CONCLUSIONS: Smoking in the prior
      20 years has a strong relation to small colorectal adenomas, smoking at least 20
      years in the past is related to larger adenomas, and the induction period for
      colorectal cancers is at least 35 years. IMPLICATIONS: Our results highlight the
      need to intensify efforts to prevent smoking, especially among the young, and
      suggest a reduced threshold for screening for colorectal cancer among long-term
      smokers.

PMID- 8283491
TI  - A prospective study of cigarette smoking and risk of colorectal adenoma and
      colorectal cancer in U.S. women.
AB  - BACKGROUND: A positive correlation between smoking and colorectal cancer has been
      reported for men, but not for women, who began smoking in substantial numbers in
      the late 1940s and early 1950s. We hypothesized that smoking acts as an initiator
      of colorectal neoplasia and that an association with cancer in women has been
      missed because of the long period between initiation and diagnosis of cancer.
      PURPOSE: Our purpose was to assess the association between smoking and risk of
      colorectal adenoma and colorectal cancer in women and to estimate the minimum
      induction period between the onset of smoking and cancer diagnosis. METHODS: Our
      data came from the ongoing Nurses' Health Study, in which current and lifetime
      smoking histories and other potential confounding factors were assessed by
      questionnaire at baseline and at 2-year intervals. We documented 586 new cases of
      colorectal cancer from 1976 to 1990 from a group of 118,334 women and 564 new
      cases of adenoma among 12,143 women who had a first colonoscopy or sigmoidoscopy
      between 1980 and 1990. We then assessed the relative risk (RR) of small adenoma,
      large adenoma (> or = 1 cm), and colorectal cancer in terms of pack-years of
      smoking. RESULTS: The amount smoked in the prior 20 years was related to the
      prevalence of small adenomas (multivariate RR = 1.45; 95% confidence interval
      [CI] = 1.25-1.68; P < .0001) and less strongly with large adenomas (RR = 1.31;
      95% CI = 1.17-1.47; P < .0001), adjusting for age, intake of saturated fat,
      dietary fiber, folate, and alcohol, body mass, family history of colorectal
      cancer, and pack-years of cigarettes smoked within the prior 20 years. Pack-years
      of cigarettes smoked more than 20 years in the past was associated with risk of
      large adenoma (multivariate RR for a 20 pack-year increment = 1.29; 95% CI = 1.01
      1.64; P trend = .04), but not of small adenoma (RR = 1.11; 95% CI = 0.93-1.34).
      Cigarette smoking was unrelated to colorectal cancer until 35 years after smoking
      began, but then became progressively more strongly related with time. Among women
      who had started smoking more than 10 cigarettes per day 35-39 years in the past,
      the RR for cancer was 1.47 (95% CI = 1.07-2.01), progressing to 1.63 (95% CI =
      1.14-2.33) after 40-44 years and 2.00 (95% CI = 1.14-3.49) after 45 years.
      CONCLUSIONS: Because the minimum induction period for colorectal cancer appears
      to be at least 35 years, an association between smoking and colorectal cancer in
      women may just now be showing up. IMPLICATIONS: Our findings suggest that
      cigarette smoking may be a previously unrecognized, preventable cause of
      colorectal cancer among women.

PMID- 8283492
TI  - A large kindred with 17q-linked breast and ovarian cancer: genetic, phenotypic,
      and genealogical analysis.
AB  - BACKGROUND: Mutation of a specific, but as yet unidentified, gene BRCA1 on
      chromosome 17q results in increased susceptibility to breast and ovarian cancer.
      It is important to know the effects of this gene in terms of the age-specific
      risks of these cancers and the potential interaction of this gene with other
      known risk factors. PURPOSE: We performed detailed studies on a large
      multigenerational family, in which there is known 17q-linked breast and ovarian
      cancer, in order to characterize the effects of the BRCA1 mutation on development
      of breast and ovarian cancer. METHODS: Data from the Utah Population Database
      were used to identify a family (identified as K2082) with a cluster of
      premenopausal breast cancer and ovarian cancer at any age. Blood samples from 195
      members of the family were obtained and these individuals were genotyped for a
      series of four chromosome 17q polymorphic markers. Information on reproductive
      history, cancer incidence and treatment, and lifestyle factors was collected on
      72 women in the family by questionnaire or through contact with living relatives.
      RESULTS: Odds in favor of linkage of breast and ovarian cancer in this family to
      the BRCA1 region of chromosome 17q are greater than 10(8) to 1. The estimated
      risks for breast or ovarian cancer because of the BRCA1 mutation in this family
      are 40% by age 50 years and 90% by age 70. No differences between affected and
      unaffected older BRCA1 gene carriers were observed for a number of known
      epidemiologic risk factors for these cancers. The gender of the parent from whom
      the mutant BRCA1 allele was inherited was significantly associated with
      phenotypic expression (P = .04). A recombinant which places BRCA1 distal to the
      marker Mfd191 was observed. CONCLUSIONS: Women with the BRCA1 mutation are at
      increased risk of developing breast and ovarian cancer. In our study population,
      the mutation appears to confer a lower risk of cancer at younger ages than found
      in previous studies. Continued interaction with family K2082 will be useful in
      longitudinal follow-up studies and in studies of the psychosocial implications of
      providing DNA diagnosis of BRCA1.

PMID- 8283493
TI  - Hair dye use and risk of fatal cancers in U.S. women.
AB  - BACKGROUND: Permanent hair dyes are used by about one third of adult American
      women. Several epidemiologic studies associate hair dye use with increased risk
      of non-Hodgkin's lymphoma and multiple myeloma. In one study, risk increased with
      more prolonged exposure to darker, more concentrated, permanent dyes. PURPOSE:
      The purpose of our study was to examine the relationship between hair dye use and
      development of certain cancers associated with hair dye use in previous studies.
      METHODS: We examined prospectively the relationship between the use of permanent
      hair dyes and selected fatal cancers in 573,369 women. The participants provided
      information in 1982 on the frequency and duration of hair dye use and the color
      of hair dye used. Death rates were measured through 1989. Relative risks (RRs)
      were computed with subjects who had not used hair dyes serving as the referent
      group, and 95% confidence intervals (CIs) were calculated on the basis of
      approximate-variance formulas. RESULTS: Women who had ever used permanent hair
      dyes showed decreased risk of all fatal cancers combined (RR = 0.93; 95% CI =
      0.89-0.98) and of urinary system cancers (RR = 0.65; 95% CI = 0.49-0.87) and no
      increase in risk of any type of hematopoietic cancer. Women who had used black
      hair dyes for 20 years (0.6% of women hair dyers) or more had increased risk of
      fatal non-Hodgkin's lymphoma (RR = 4.37; 95% CI = 1.3-15.2) and multiple myeloma
      (RR = 4.39; 95% CI = 1.1-18.3). These positive findings are based on three cases
      of non-Hodgkin's lymphoma and two cases of multiple myeloma. We found no
      relationship between use of permanent hair dyes and fatal cancers of the mouth,
      breast, lung, bladder, or cervix, areas that were of interest as the result of
      earlier studies. CONCLUSIONS: Women using permanent hair dyes are not generally
      at increased risk of fatal cancer. Women with prolonged use of dark, particularly
      black, hair dyes may have increased risk of fatal non-Hodgkin's lymphoma and
      multiple myeloma, but these women are a small fraction of hair dye users.
      Nonetheless, the removal of carcinogens from hair dyes and appropriate labeling
      of hair-coloring products would help reduce this potential risk.

PMID- 8283494
TI  - Monoclonal antibodies against human breast tumor-associated antigens:
      characterization of B21 antigen.
AB  - BACKGROUND: Monoclonal antibodies (MAbs) show promise in the early detection and
      monitoring of cancer and may have therapeutic applications as well. PURPOSE: The
      purpose of this study was to characterize MAb B21, a novel murine-derived
      antibody that has strong reactivity with MCF-7 and T47D cell lines from human
      breast cancer. METHODS: A number of MAbs that react with breast cancer cell lines
      were obtained from cultured mouse spleen cells, and one, MAb B21, was selected
      for detailed analysis. MAb B21 was characterized by immunocytochemical,
      immunofluorescence, immunoprecipitation, and Western blotting procedures.
      RESULTS: We found a strong reactivity of MAb B21 with cultured breast cancer
      cells and cells from human breast tumors, although some reactivity was seen
      sporadically in non-breast or normal tissue. Negligible reactivity was detected
      in a series of non-breast cell lines and with normal breast epithelial cell line
      MCF-10A. However, when MCF-10A cells were permeabilized, allowing the antibody to
      penetrate within the cells, reaction became apparent. MCF-10A cells, when
      transfected with the oncogene c-Ha-ras (MCF-10T), gave a positive immunostaining
      similar to that observed with MCF-7 and T47D cells. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) analysis of L-[35S]methionine
      labeled MCF-7 and T47D cell extracts showed distinct immunoprecipitated
      components, with molecular weight values ranging from 150,000 to 20,000 with the
      addition of MAb B21. Western blot assays using MAb B21 of SDS-PAGE
      fractionated/electroblotted proteins from breast cancer cell lines and MCF-10A
      cells showed specific reaction with a 95,000 component. CONCLUSIONS: Our results
      indicate that B21 antigen is expressed in neoplastic cells of epithelial origin,
      mainly breast cancer, and to a minor extent in other cell lines. In addition, MAb
      B21 recognizes an antigen that is differentially localized during cell
      transformation. IMPLICATIONS: Our future studies will address the full
      characterization of MAb B21 and explore its capacity as a tool for therapeutic
      manipulation.

PMID- 8283495
TI  - Sensitivity of multiple myeloma to imexon in the human tumor cloning assay.

PMID- 8283496
TI  - Forty-two-year prostatic cancer incidence trends in a defined population of one
      million served by a reimbursement-linked cancer registry.

PMID- 8283497
TI  - High organochlorine body burden in women with estrogen receptor-positive breast
      cancer.

PMID- 8283498
TI  - Local production of interleukin 6 by renal adenocarcinoma in vivo.

PMID- 8283499
TI  - Re: Doctors debate different breast biopsy techniques.

PMID- 8283500
TI  - The transotic approach in acoustic neuroma surgery.
AB  - A consecutive series of 147 transotic operations for the removal of acoustic
      neuroma is presented. The advantages of this approach over the conventional
      translabyrinthine technique are several, including 1) a wider surgical access
      with a circumferential exposure of the internal acoustic meatus and the porus
      acousticus; 2) the direct visualization and access to the anterior
      cerebellopontine angle where the facial nerve is usually tenuous and most
      vulnerable; and 3) the permanent closure of the ear canal and eustachian tube
      with complete obliteration of the surgical cavity, minimizing cerebrospinal fluid
      leaks. These advantages have translated into improved surgical outcomes. In our
      series of 147 patients spanning 11 years, total tumor extirpation was achieved in
      all patients, with one mortality, three CSF leaks, and one meningitis. The facial
      nerve was anatomically preserved in 95% of the cases. This approach is capable of
      attaining the widest, and the most direct access to the cerebellopontine angle
      without cerebellar retraction.

PMID- 8283501
TI  - Cogan's syndrome: a review of otologic management and 10-year follow-up of a
      pediatric case.
AB  - Although first characterized over 45 years ago Cogan's syndrome still remains a
      rare disease, with a high incidence of poor outcome. Experience with a case of
      Cogan's syndrome over a 10-year period is presented. The fluctuating clinical
      evolution and laboratory findings over this period are depicted, starting from
      presentation at age 10. The response to treatment, as revealed by audiograms, is
      traced. The literature is reviewed with regard to treatments that have been
      proposed. In those cases where a sustained follow-up is available, the success of
      the therapy on the vestibuloauditory system is evaluated. Although some patients
      have a positive response to steroids, the prognosis for hearing remains poor. The
      ability of steroids to change the prognosis for hearing loss is not yet
      established, but warrants further clinical trial.

PMID- 8283502
TI  - Beta-2 transferrin assay in clinical management of cerebral spinal fluid and
      perilymphatic fluid leaks.
AB  - Beta-2 transferrin is a protein found in cerebral spinal fluid (CSF) and inner
      ear perilymph, but not in blood, nasal or ear secretions. The purpose of this
      paper is to evaluate the clinical usefulness of the current assay for beta-2
      transferrin for detecting CSF and perilymphatic leaks. We reviewed the hospital
      records of the first 88 patients having specimens submitted for beta-2
      transferrin analysis at our institution. Both CSF and perilymph leaks were
      identified. However, confirmation of the absence or presence of beta-2
      transferrin was directly used in the clinical management of only 55% of the
      patients. This was largely secondary to the time delay in test processing and
      initial lack of physician confidence with the test. However, our review of the
      clinical outcomes relating to the use of the beta-2 transferrin analysis suggests
      high sensitivity and specificity for the test. Analysis of beta-2 transferrin
      appears to be a valuable test for detecting CSF leakage and a promising test for
      confirming perilymphatic leaks. However, to achieve greater clinical usefulness a
      rapid clinical assay needs to be developed and further information gained
      regarding the sensitivity and specificity of the beta-2 transferrin assay for
      detecting CSF and perilymphatic fluid leakage.

PMID- 8283503
TI  - Cochlear implants and otitis media: considerations in two cleft palate patients.
AB  - Cochlear implantation is a safe and effective means of rehabilitating profound
      sensory deafness. The implications of coincident chronic middle ear disease upon
      the operative procedure and auditory results have received little attention in
      the literature. We describe two patients, each with congenital cleft lip and
      palate and secondary chronic otitis media with effusion, who received
      multichannel cochlear implants following bacterial meningitis. One patient (a
      three-year-old girl) was implanted in the standard fashion while the other (a 38
      year-old-man) underwent middle ear and mastoid obliteration. Our findings suggest
      that chronic otitis media should not be a deterrent to cochlear implantation.

PMID- 8283504
TI  - Interaction of saccadic and vestibular mechanisms in combined eye-head gaze
      shifts.
AB  - Saccades are the only purely volitional eye movements available to primates. They
      are used extensively to acquire new or interesting targets in the visual
      environment. Most patients with saccadic disorders are referred to neurologists.
      Patients complaining of disorientation, however, are often presumed to be
      suffering from a vestibular disorder. Vestibular and saccadic physiology has been
      studied mostly in isolation of each other. We examine the interaction of saccadic
      burst neurons and vestibular signals to achieve accurate gaze shifts.

PMID- 8283505
TI  - Sound localization with hearing protectors.
AB  - A preliminary investigation was conducted of the ability of normal-hearing
      subjects to localize sound while wearing hearing protective devices. Performance
      with Bilsom 2392 level-dependent stereophonic muffs with limited amplification
      was compared with that of conventional level-independent E-A-R 3000 muffs and E-A
      R plugs. Sound localization was assessed using an array of six speakers,
      positioned in the horizontal plane, 1 m from the subject at azimuth angles of 30
      degrees, 90 degrees, 150 degrees, 210 degrees, 270 degrees and 330 degrees. The
      stimulus was an 80 dB SPL 300-ms one-third octave noise band centered at 500 Hz
      or 4000 Hz. The experiment was conducted in quiet and in a 65 dB SPL white noise
      background. The results indicated that at 500 Hz, the wearing of protectors
      resulted in a 20% decrease in the accuracy of speaker identification but the
      three types of device were indistinguishable. At 4000 Hz, performance was best in
      the unoccluded condition and relatively worst with the level-dependent muff.
      Error patterns depended on the interaction of stimulus frequency, speaker azimuth
      and protector. Front/back errors in localizing the high-frequency stimulus were
      greatest with the conventional muff, whereas right/left errors were greatest with
      the level-dependent muff. Protected listening was generally unaffected by the
      presence of a noise background for both of the frequencies tested.

PMID- 8283506
TI  - Wegener's granulomatosis: otological aspects.
AB  - Otological presentations are uncommon in Wegener's granulomatosis. We report a
      series of cases in which ear disease was a major manifestation of the disease and
      discuss the otogenic and neurological manifestations of Wegener's granulomatosis.

PMID- 8283507
TI  - Differentiation of balance deficits through examination of selected components of
      static stabilometry.
AB  - Stabilometry, which measures the body's center of pressure (COP) movements,
      during relaxed standing, has been used to distinguish individuals with vestibular
      and neurologic dysfunctions from normal subjects. The purpose of this study was
      to determine whether mathematical differences in the magnitudes of the COP
      obtained from six somatosensory testing conditions could be used to discriminate
      between different types of balance deficits. Stabilometry measures, using a fixed
      force platform, were obtained from normal (N = 52) and dizzy (N = 149),
      peripheral vestibular dysfunction (PVD), post-concussion syndrome (PCS),
      psychogenic (PSG), and unknown/undetermined etiology (UNK). The data
      significantly differentiated CVD, PVD and PSG patients from normals and between
      some of the dizzy groups: CVD versus PVD, PCS; and PSG versus CVD, PVD, PCS and
      UNK. The measures of anterior-posterior COP movements provided the greatest
      discrimination.

PMID- 8283508
TI  - A study into the phenomenon of head-shaking nystagmus: its presence in a dizzy
      population.
AB  - In this paper we have prospectively analyzed results from approximately 1,500
      patients who underwent a head-shaking test during routine electronystagmography
      (ENG). The incidence of head-shaking nystagmus (HSN) in a dizzy population was
      relatively high (31.7%) when compared to other so-called abnormalities in the
      routine ENG test battery. Its presence was also similar in both active vs.
      passive head-shake tests. When present, different types of HSN were identified
      (monophasic (76.8%), biphasic (22.7%) and triphasic (0.5%)). In some cases,
      reversals of the expected "normal" pattern occurred. A high correlation was found
      to exist between a positive head-shake test and the presence of spontaneous
      nystagmus, positional nystagmus and caloric test abnormalities.

PMID- 8283509
TI  - Tissue culture of middle ear epithelium using fibroblast-reorganized collagen
      gels.
AB  - The middle ear epithelium of the guinea pig has been cultured on a modified
      floating collagen matrix. Fibroblasts harvested from abdominal skin dermis of
      allogenic animals were used to reorganize hydrated collagen gels into a dermal
      like matrix. Within two days, the explants placed on the surface of these
      matrices showed proliferation of polygonal "outgrowth cells" which could be
      maintained for up to one month. During the first two weeks of the culture period,
      dividing cells were frequently identified. These cells were especially abundant
      in the marginal area of the explants and consisted of pseudostratified columnar
      cells. The reorganized collagen gel matrix was stable and did not dissolve even
      after the "outgrowth cells" became confluent. The present system should allow
      further elucidation of the growth and differentiation mechanisms of middle ear
      epithelial cells.

PMID- 8283510
TI  - A survey of auditory brainstem nuclei in the chicken (Gallus domesticus) with
      cytochrome oxidase histochemistry.
AB  - The chicken's auditory brainstem nuclei from the cochlear nuclei to the nuclei of
      the lateral leminiscus were studied with cytochrome oxidase histochemistry. A
      strong reactivity in the cochlear and laminar nuclei was confirmed. Additional
      structures displaying high activity levels include the superior olive and both
      partitions of the nucleus intermedius lemnisci lateralis. Unilateral cochlea
      removal led to a strong reduction of activity in the cochlear nuclei and the
      nucleus laminaris, whereas there was no remarkable effect in higher brainstem
      centers. After bilateral cochlea extirpation auditory structures still displayed
      higher enzyme levels than most other nuclei. These observations point to the
      extraordinary metabolic activity in the ascending auditory pathway which is
      largely independent of sensory input from the auditory nerve.

PMID- 8283511
TI  - A survey of the auditory midbrain, thalamus and forebrain in the chicken (Gallus
      domesticus) with cytochrome oxidase histochemistry.
AB  - The chicken's central auditory nuclei from the inferior colliculus to field L in
      the forebrain were studied with cytochrome oxidase histochemistry. All stations
      of the ascending pathway displayed high activity levels, including the inferior
      colliculus, the nucleus ovoidalis of the thalamus, and field L1 to L3 and the
      hyperstriatum ventrale caudale which correspond to primary and secondary auditory
      cortex. In the inferior colliculus a moderately active external nucleus could be
      distinguished from a more intensely stained central and superficial nucleus. In
      the central nucleus there was a lateral shell displaying stronger neuropil
      reactivity than a central core. Unilateral cochlea removal caused no remarkable
      effect in tectum and thalamus. The auditory forebrain contralateral to the lesion
      displayed reduced CO reactivity compared with the ipsilateral side. After
      bilateral cochlea extirpation auditory structures still displayed higher enzyme
      levels than most other nuclei.

PMID- 8283512
TI  - Laryngeal tuberculosis.

PMID- 8283513
TI  - A brief history of urethral catheterization.

PMID- 8283514
TI  - Renal masses: value of duplex Doppler ultrasound in the differential diagnosis.
AB  - In a prospective study, 84 nonanechoic renal masses were examined with duplex
      Doppler ultrasound with a 3.5 mHz. transducer. This study included malignant
      lesions in 49 cases (30 renal carcinomas, 9 metastases, 8 lymphomas and 2
      sarcomas) and benign lesions in 35 (18 complicated cysts, 6 inflammatory
      processes, 5 columns of Bertin, 3 angiomyolipomas and 3 hematomas). We analyzed
      whether duplex Doppler ultrasound can have a role in the differential diagnoses
      of these solid renal masses. Renal carcinomas demonstrated Doppler shifts of 2.5
      kHz. or more in 23 cases (77%). These masses had significantly higher Doppler
      shifts than all of the other malignant masses (p < 0.001). Among the benign
      lesions the Doppler shifts were less than 2.5 kHz. in 33 cases (84%). The 2
      masses with a Doppler shift of more than 2.5 kHz. in this group were inflammatory
      lesions. Detection of a Doppler shift of 2.5 or greater in a renal mass supports
      suspicion of a renal cell carcinoma, although an inflammatory process may also
      produce such a high Doppler shift. Doppler shifts of less than 2.5 kHz. in solid
      renal masses support the diagnoses of a benign lesion and a malignant lesion
      other than renal cell carcinoma.

PMID- 8283515
TI  - The incidence of urinary tract infection in patients without bacteriuria who
      underwent extracorporeal shock wave lithotripsy.
AB  - The incidence and severity of urinary tract infections in 145 patients with renal
      calculi undergoing extracorporeal shock wave lithotripsy (ESWL*) who were
      catheterized for a short period without evidence of bacteriuria and/or infected
      stones evaluated. The patients were followed clinically and bacteriologically 1
      and 14 days after the procedure. Bacteriuria was observed in 7 of the 145
      patients (4.8%): in 5 patients 24 hours after ESWL and in 2 patients 2 weeks
      later. Of these patients 2 were symptomatic but only 1 had fever. No patient was
      hospitalized. We found no correlation between bacteriuria and the number or size
      of the stones. We conclude that the incidence of bacteriuria in catheterized
      patients who underwent ESWL without urinary tract infection is low and the use of
      antibiotics in these patients is probably not indicated.

PMID- 8283516
TI  - Late complications of the modified Indiana pouch.
AB  - The modified Indiana pouch is currently an accepted and widely used form of
      continent cutaneous urinary diversion. However, results of long-term followup and
      potential late complications are still being established. We report our
      experience with 130 modified Indiana pouches performed between September 1987 and
      September 30, 1991. In 16 patients (12%) late complications developed between 1
      and 16 months after the pouch procedure. Ureteral obstruction developed in 9 of
      these patients (7%), including bilateral obstruction in 4. Balloon dilation with
      or without incision of ureteral strictures in 6 patients resulted in an 83%
      failure rate, while ureteral reimplantation was successful in 91% (10 of 11
      cases). Reservoir dysfunction was the late complication in the remaining 7
      patients. Urodynamic evaluation was essential in determining appropriate
      treatment for incontinence with either replication of the ileal segment or pouch
      augmentation with an ileal patch. Of the 16 late complications 56% occurred in
      patients who received between 3,000 and 6,500 rad of pelvic radiation before the
      urinary diversion. We conclude that the modified Indiana pouch is a successful
      form of urinary diversion with an acceptable complication rate. Ureteral balloon
      dilation with or without endoscopic incision of ureteral strictures has not been
      successful. However, patients can usually undergo successful ureteral
      reimplantation via an extraperitoneal approach with minimal morbidity. Previously
      radiated patients are at higher risk for complications and require shorter
      ureteral tunnels to avoid stricture, in addition to an ileal patch at initial
      construction.

PMID- 8283517
TI  - Absorption of sodium and chloride in continent reservoirs for urine: comparison
      of ileal and colonic reservoirs.
AB  - The absorptive capacity of urinary reservoir mucosa was studied by measuring the
      fractions of 22sodium and 36chloride absorbed after instillation into reservoirs
      constructed from an ileal or a colonic segment. The absorption of 22sodium did
      not differ between the 2 reservoir types but absorption of 36chloride was greater
      in the colonic reservoirs. The levels of chloride in serum were significantly
      higher in patients with a colonic than in those with an ileal reservoir. In the
      ileal reservoirs the absorptive capacity was greater for 22sodium than for
      36chloride.

PMID- 8283518
TI  - Stenosis of the afferent antireflux valve in the Kock pouch continent urinary
      diversion: diagnosis and management.
AB  - Between August 1982 and May 1988, 503 patients underwent construction of a
      continent ileal reservoir (Kock pouch) for cutaneous urinary diversion at our
      university. Stenosis of the afferent antireflux valve resulted in upper urinary
      tract obstruction in 11 patients (2%). In addition, 2 patients underwent Kock
      pouch diversion elsewhere and upon referral to our institution they had afferent
      valve stenosis. To date 13 patients have been identified with this problem.
      Hydronephrosis was present in 100% of the functional kidneys in these patients.
      Radiographs of the Kock pouch were uniformly normal without evidence of reflux or
      other pathological condition. The most common presenting symptom was flank pain
      in 7 patients (54%) and the most common presenting sign was creatinine elevation
      above baseline in 7 (54%). Infections recurred with or without sepsis in 5
      patients (38%). Ureteroileal anastomotic strictures were not present in any
      patient. The interval from creation of the Kock pouch to the diagnosis of
      stenosis ranged from 2 to 75 months (mean 39). All patients underwent endoscopic
      evaluation of the Kock pouch confirming stenosis of the afferent antireflux
      valve, and subsequent mechanical dilation of the stenotic valve. Dilation
      procedures were repeated in 6 patients (46%), 4 of whom subsequently required
      open surgical revision of the afferent valve. Of these patients 3 are clinically
      stable and 1 died of the primary malignancy. The remaining 2 patients are
      clinically and radiographically stable after multiple dilations. Of the 7
      patients (54%) requiring only a single dilation 6 are clinically stable and 1
      died of the primary malignancy. Stenosis of the afferent antireflux valve of the
      Kock pouch, previously unreported to our knowledge, is a rare late complication
      leading to flank pain, hydronephrosis, recurrent infection and elevation of serum
      creatinine levels. Approximately 50% of the patients respond to a single dilation
      of the nipple valve. However, most patients who require repeat dilation will need
      open surgical revision.

PMID- 8283519
TI  - Continent urinary reservoirs.

PMID- 8283520
TI  - Decreased expression of a glycoprotein component of bladder surface mucin (GP1)
      in interstitial cystitis.
AB  - Interstitial cystitis is a disease of unknown etiology characterized by
      unremitting urinary frequency, urgency and suprapubic pain. Recently, a change in
      urothelial permeability has been identified in interstitial cystitis patients
      that is presumably mediated by aberrations in bladder surface mucin. For this
      study we evaluated qualitative changes in a previously defined glycoprotein
      component of this layer (GP1) as it occurs in interstitial cystitis patients and
      normal controls. Paraffinized bladder biopsies were obtained from 23 interstitial
      cystitis patients (all meeting National Institutes of Health inclusion criteria)
      and 11 normal controls. All biopsy tissue was stained with hematoxylin and eosin,
      and periodic acid, Schiff reaction. The tissues were examined
      immunohistochemically for GP1 using an anti-GP1 serum. Periodic acid, Schiff
      staining clearly identified bladder surface proteoglycans in all specimens.
      Moderate GP1 reactivity was noted in all normal control specimens. Alternatively,
      GP1 expression was absent in 35% of the interstitial cystitis patient biopsies
      and decreased in 61%. These data demonstrate qualitative GP1 changes in a
      majority of interstitial cystitis patients. It is unknown whether these
      differences have an impact on the pathogenesis of interstitial cystitis. However,
      our findings suggest that the absence or decreased expression of GP1 in
      interstitial cystitis bladder biopsies may serve as a marker to characterize the
      disease further in conjunction with clinical findings.

PMID- 8283521
TI  - Bladder permeability in interstitial cystitis is similar to that of normal
      volunteers: direct measurement by transvesical absorption of 99mtechnetium
      diethylenetriaminepentaacetic acid.
AB  - Bladder permeability was directly measured with the radionuclide used clinically
      for detecting vesicoureteral reflux (99mtechnetium-diethylenetriaminepentaacetic
      acid, 99mTc-DTPA) in 10 interstitial cystitis patients diagnosed according to
      National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases
      criterion and compared to 9 sex matched, symptom-free, normal volunteers. After
      functional bladder capacity was determined (capacity at which the patient demands
      fluid inflow to stop), the bladder was emptied and 5 mCi. 99mTc-DTPA in 10 ml. of
      saline were infused followed by normal saline to 80% of functional capacity. This
      was done to normalize the patients to the same low bladder pressure, since
      previous studies of rabbits indicated that bladder permeability is low and not
      significantly different at 20% and 60% of anesthetized bladder capacity (defined
      as the volume producing an intravesical pressure of 20 cm. water). Radioactivity
      of 1 ml. serum specimens taken at 0, 2, 15 and 30 minutes after radionuclide
      infusion was determined in a gamma counter, corrected for radioactive decay and
      converted to per cent of instilled dose per whole body based on blood volume
      estimated from body weight for each individual. There was considerable
      interindividual variability in the absorption between the patients and the
      volunteers. Analysis of variance of these data showed no statistically
      significant difference between the patients and controls at any time sampled.
      These results indicate that while some interstitial cystitis patients have a more
      permeable bladder than others, the same is true for normal, symptom-free
      volunteers. Thus, the concept of increased bladder permeability in interstitial
      cystitis is not supported by this direct measurement of bladder permeability.

PMID- 8283523
TI  - Interstitial cystitis.

PMID- 8283522
TI  - Complement C3, eosinophil cationic protein and symptom evaluation in interstitial
      cystitis.
AB  - Interstitial cystitis is a painful, irritative voiding dysfunction of unknown
      etiology. In this study 19 women undergoing treatment for interstitial cystitis
      and 6 healthy women of similar age provided 2 urine and serum specimens with at
      least a 3-month interval between collections. Complement C3 and eosinophil
      cationic protein were determined by immunoassay methods, and symptom severity was
      quantitated with a visual analog scale questionnaire. Concentrations of
      complement C3 and eosinophil cationic protein from either serum or urine were not
      significantly different between interstitial cystitis patients and controls at
      either determination, although substantial differences were noted even between
      individual initial and followup determinations. Normalization of urine osmolality
      did not alter these results. Symptom severity scores were significantly greater
      in interstitial cystitis patients compared to controls but failed to correlate
      with the concentrations of complement C3 or eosinophil cationic protein.
      Therefore, the hypothesis that complement C3 and eosinophil cationic protein may
      be etiological factors of interstitial cystitis is not supported.

PMID- 8283524
TI  - An alternative in surgical treatment of post-irradiation vesicovaginal and
      rectovaginal fistulas: the seromuscular intestinal graft (patch).
AB  - The excellent results experienced with the use of seromuscular intestinal grafts
      in certain types of urological plastic operations encouraged us to use it (as a
      patch) also in the surgical management of vesicovaginal and rectovaginal
      fistulas. With this method, we treated 4 patients with post-irradiation fistulas
      who had previously undergone 1 or 2 operations. The seromuscular intestinal graft
      served as a direct partial wall replacement of the bladder or rectum. At the same
      time, it also supported the nutrition of the compromised tissues surrounding the
      fistula. There were no complications with epithelialization of the denuded
      muscular surface of the seromuscular intestinal graft (patch) facing into the
      bladder.

PMID- 8283525
TI  - Oncogenic human papillomaviruses are rarely associated with squamous cell
      carcinoma of the bladder: evaluation by differential polymerase chain reaction.
AB  - While a strong association between oncogenic human papillomaviruses and squamous
      cell cancers of the genital tract (penis, urethra and cervix) is known to exist,
      there is substantial controversy regarding the association of human
      papillomaviruses and cancers of the bladder. Technical issues regarding assay
      technique and concern about potential contamination have marred interpretation of
      previous work. Moreover, because human papillomavirus has been associated
      predominantly with squamous cell cancers at other sites, any involvement of human
      papillomavirus and bladder epithelial carcinogenesis must address whether any
      association between human papillomavirus and squamous cell carcinoma of the
      bladder exists. Differential polymerase chain reaction and a rigorous protocol to
      avoid crossover contamination were used to analyze archival bladder carcinoma
      specimens (22 squamous cell carcinomas and 20 transitional cell carcinomas). Type
      specific primers for human papillomavirus types 16 and 18 were used as were
      general primers to detect types 6b, 11, 13, 16, 18, 31, 32, 33, 35, 45 and 51.
      Only 1 of 22 squamous cell carcinoma specimens (4.4%) was positive (human
      papillomavirus type 18)--a cadaveric renal transplant patient on chronic
      immunosuppression. Cervical specimens were human papillomavirus negative in this
      patient. No human papillomavirus deoxyribonucleic acid was detected in the 20
      transitional cell carcinoma cohort. Our results confirm that these human
      papillomavirus types appear to have little association with invasive transitional
      cell cancers. Of greater significance, despite this (to our knowledge) first
      reported case of human papillomavirus type 18 detected in squamous cell carcinoma
      of the bladder (seen in an immunocompromised patient), we conclude that these
      oncogenic human papillomavirus types do not have a significant role in squamous
      cell carcinogenesis of the bladder.

PMID- 8283526
TI  - Urachal carcinoma: the case for extended partial cystectomy.
AB  - A total of 12 patients with urachal carcinoma was managed by extended partial
      cystectomy. Of these 12 patients 10 were free of disease at 1 to 13 years,
      including 8 beyond 2 years. No patient had a pelvic or bladder recurrence. Early
      diagnosis of a contained urachal tumor favored complete resection by wide
      surgical excision and a good prognosis.

PMID- 8283527
TI  - Single potential analysis of cavernous electrical activity in spinal cord injury
      patients.
AB  - Introduced in 1988, cavernous electromyography and its evolution, single
      potential analysis of cavernous electrical activity (SPACE), seem to be promising
      diagnostic methods in the evaluation of erectile dysfunction. The aim of our
      study was to determine the influence of a centrally disturbed autonomic supply on
      SPACE recordings. SPACE was performed in 35 male patients with complete and 2
      with incomplete spinal cord lesions at a cervical or thoracic level. Simultaneous
      recording was done with concentric needle electrodes in both cavernous bodies
      with a frequency range of 0.5 to 100 Hz. All patients underwent a full
      neurological and urological evaluation, including cystometry. The lesion was
      cervical in 12 patients and thoracic in 22. Three patients underwent sacral
      deafferentation and bladder pacemaker implantation. One of 12 patients with
      cervical and 10 of 22 with thoracic lesions reported full rigid reflexogenic
      erections, while 3 of 12 patients with cervical lesions were not evaluable due to
      grounding failure. Of these patients 31 were eligible for our study. No patient
      had an entirely normal SPACE. Four of 9 patients with cervical and 19 of 22 with
      thoracic lesions had a normal, silent basic electric (less than 5 mu v.)
      oscillation, while the remainder had a baseline oscillation of up to 100 mu v.
      Normal potentials were found in 2 of 9 and 10 of 22 patients, respectively. Low
      frequency, high amplitude potentials were found in 6 of 9 and 21 of 22 patients,
      respectively, while low frequency, low amplitude potentials occurred in 8 and 8,
      respectively, and high frequency potentials occurred in 5 and 1, respectively.
      Our results show that abnormal autonomic input induces abnormal SPACE findings in
      patients with (presumably) normal cavernous tissue.

PMID- 8283528
TI  - Vascular abnormalities in Peyronie's disease: the role of color Doppler
      sonography.
AB  - We attempted to clarify the role of color Doppler sonography in assessing the
      vascular function of untreated Peyronie's disease. A total of 50 patients with a
      mean 20-month history of penile curvature underwent color Doppler sonography with
      the penis in the flaccid state and after intracavernous injection of 20
      micrograms. prostaglandin E1. Of the patients 41 (82%) complained of various
      degrees of erectile dysfunction, while 9 (18%) reported sustained rigid
      erections. Pathological peak systolic flow velocities (less than 30 cm. per
      second) of the cavernous arteries were found bilaterally in 10 patients (20%) and
      unilaterally in 10 (20%). Peak systolic flow velocity correlated positively with
      cavernous artery flow volume and with acceleration. Cavernous artery end
      diastolic velocity and resistance index, measured 15 and 30 minutes after
      vasoactive injection and genital manipulation, were indicative of corporeal veno
      occlusive dysfunction (greater than 10 and less than 0.75 cm. per second,
      respectively) in 32 patients (65%). Of these patients, 11 (22%) had mixed
      arteriovenous dysfunction and 9 (18%) had normal cavernous artery flow
      velocities. Flow along the cavernous arteries is sometimes altered in cases of
      Peyronie's disease while corporeal veno-occlusive dysfunction seems to be the
      main hemodynamic abnormality. Color Doppler sonography should be considered as
      the initial step in the diagnostic evaluation of patients with Peyronie's disease
      who may be eligible for surgical treatment.

PMID- 8283529
TI  - A functional analysis and the potential clinical significance of 7 categories of
      sperm morphology.
AB  - Sperm morphology is a critical factor in the evaluation of infertile men.
      Patients often exhibit a morphology profile with consistent increases of specific
      abnormal categories of sperm morphology. We analyzed the functional ability of 7
      categories of sperm morphology using assays that measure sperm viability
      longevity, deoxyribonucleic acid packing, acrosomal status, and the stimulation
      of the acrosome reaction with human cumulus/oocyte complexes and calcium
      ionophore A23187. Each morphology category was separately analyzed initially and
      at 3, 6, 12, 18 and 24 hours of in vitro culture. The data indicate that all
      categories of abnormal sperm morphology exhibit various functional debilities.
      However, tapered sperm most closely approached normal sperm function. All
      abnormal categories possessed subpopulations of sperm that functioned normally to
      the limits of these assays. These data indicate that increases in any of the
      categories of abnormal sperm morphology may lead to decreased fertility due to
      diminished functional ability indicated by the assays performed in this study.

PMID- 8283530
TI  - Antegrade scrotal sclerotherapy for the treatment of varicocele: technique and
      late results.
AB  - Antegrade sclerotherapy has been used since 1987 to treat patients with
      varicocele. The method has proved to be easy to perform, safe, economical and
      effective. The treatment results in 285 patients who had undergone sclerotherapy
      for a total of 317 varicoceles are presented and discussed. This followup study
      revealed that 285 of the patients (91%) had no signs of recurrent or persistent
      varicocele. In 57 cases (42%) of inability to conceive the partners became
      pregnant after antegrade varicocele sclerotherapy. Antegrade sclerotherapy
      represents an alternative treatment to high ligation and retrograde
      sclerotherapy, as well as to laparoscopic and microsurgical procedures.

PMID- 8283531
TI  - Stryker frame adaptation of the HM3 lithotriptor for treatment of distal ureteral
      calculi.
AB  - Treatment of distal ureteral stones with the Dornier HM3 lithotriptor depends on
      the localization and positioning of the calculus from a transgluteal approach. We
      found the Stryker frame gantry modification preferable to the standard gantry for
      treatment of stones in the distal ureter. We report the use of this gantry
      adaptation in 22 cases of distal ureteral stones. The calculi were localized in
      100% of the cases and were fragmented successfully with 1 treatment in 89%. In no
      case was the procedure aborted secondary to nonvisualization of the calculus.
      Failure to disintegrate the stone requiring retreatment occurred in 11% of the
      cases, and was attributed to stone characteristics and not due to difficulty with
      visualization or placement of the calculus within the F2 focus. The average
      fluoroscopic time was 45 seconds. The Stryker frame modification to the standard
      Dornier HM3 lithotriptor allows for improved visualization and easier
      localization of distal ureteral calculi compared to the standard gantry.

PMID- 8283532
TI  - Dorsal nerve block for management of intraoperative penile erection.
AB  - Intraoperative penile erection during general anesthesia can delay or prevent the
      completion of cystoscopic or penile surgical procedures. The dorsal penile nerve
      block is offered as a treatment for intraoperative erection. Advantages of this
      technique include less potential for cardiovascular complications and improved
      postoperative analgesia.

PMID- 8283533
TI  - Enteric hyperoxaluria associated with external biliary drainage.
AB  - Several chronic disorders of small bowel function have been associated with
      enteric hyperoxaluria. We report on a patient in whom enteric hyperoxaluria and
      recurrent calcium oxalate calculi developed during treatment with temporary
      external biliary drainage for sclerosing cholangitis. The hyperoxaluria
      subsequently resolved with reestablishment of intraluminal biliary flow at
      successful liver transplantation. We propose a mechanism for this previously
      unrecognized cause of hyperoxaluria.

PMID- 8283534
TI  - Medical therapy alone for the treatment of gas forming intrarenal abscess.
AB  - Gas forming renal infections are severe, potentially lethal conditions. Gas
      formation in an intrarenal abscess is extremely rare. Formerly, these patients
      were uniformly treated by a combined medical and surgical approach. We describe 2
      patients with intrarenal gas abscess who were successfully treated with
      antibiotics alone. We review the literature concerning intrarenal gas abscess and
      propose a pathophysiological mechanism for its formation as well as a treatment
      schema.

PMID- 8283535
TI  - Treatment of sickle cell trait hematuria with oral urea.
AB  - Unilateral hematuria is a vaso-occlusive complication of the sickle syndromes,
      especially the sickle cell trait. Treatment is usually ineffective, and the
      duration is variable, often prolonged and subject to recurrences. In sickle cell
      trait hematuria is usually the only consequence of sickling, possibly because the
      unique renal countercurrent mechanism may result in a milieu more prone to
      sickling in the medullary circulation than in the vasculature of other organs.
      Urea in vitro inhibits gelation of deoxygenated sickle hemoglobin. In 2
      previously reported cases of sickle cell trait hematuria ceased within 3 days
      with oral urea therapy. We describe another such patient in whom hematuria also
      ceased by day 3 with oral urea. Although clinical trails with intravenous urea
      were ineffective in shortening the course of sickle crisis, urea may have an
      enhanced effectiveness in the renal medulla where the propensity for sickling may
      be much greater than in other organs. If these observations are confirmed in a
      controlled study, oral urea therapy would emerge as an effective, relatively
      innocuous and inexpensive treatment for this frustrating condition.

PMID- 8283536
TI  - The Klippel-Trenaunay syndrome: a rare cause of hematuria requiring nephrectomy.
AB  - The Klippel-Trenaunay syndrome is a rare disorder in which the congenital
      vascular anomalies can affect the urogenital tract. Several cases of hemorrhage
      from the urogenital system have been reported in children with this condition. We
      report an upper renal tract hemorrhage in an adult, which required nephrectomy.
      To our knowledge this condition has not been reported previously in an adult with
      the Klippel-Trenaunay syndrome. We discuss the condition, and its diagnosis,
      treatment and relevance to the urogenital tract.

PMID- 8283537
TI  - Renal transplantation using external continent urinary diversion.
AB  - A 29-year-old man born with bladder exstrophy presented with end stage renal
      failure many years after ileal conduit diversion. Bilateral nephrectomy and
      continent external urinary diversion were performed, and 1.5 months later a
      cadaveric kidney was grafted into the right iliac fossa. The patient was well at
      18 months with a serum creatinine level of 1.2 mg./dl. and he was completely dry
      with 4 or 5 daily catheterizations. Although followup is still short, renal
      transplantation with drainage into an external continent urinary diversion
      permits excellent quality of life and good renal function. Therefore, this
      alternative is worth consideration whenever other reconstructive alternatives are
      not possible in candidates for renal transplantation.

PMID- 8283538
TI  - Hematuria, renal mass and amenorrhea: indicators of a rare diagnosis.
AB  - Metastatic choriocarcinoma of the kidney is a rare entity, and its primary
      presentation with hematuria and renal mass is even less common. Two cases are
      presented with a review of the literature.

PMID- 8283539
TI  - Recombinant interferon-alpha efficacy in relapsed adult nephroblastoma: a case
      report.
AB  - We report on a 37-year-old woman with progressive lung and pleural metastases
      from a right nephroblastoma, who achieved partial remission with recombinant
      interferon-alpha. The drug was given subcutaneously at a dose of 5 mu. 3 times
      per week. The response was documented after 3 months of treatment and was
      maintained for at least 9 months. Although such a response has not been reported
      in the literature, this case suggests promising activity of recombinant
      interferon-alpha in relapsed nephroblastoma.

PMID- 8283540
TI  - Multiple retroperitoneal schwannomas: case report and review of the literature.
AB  - We report a rare case of multiple retroperitoneal schwannomas, initially believed
      to be an adrenal carcinoma with metastasis. These benign tumors were discovered
      in a patient presenting with vague back pain. Preoperative radiographic and
      endocrine evaluations suggested a nonfunctioning adrenal tumor. The final
      diagnosis and its juxta-adrenal origin were confirmed by histological and
      immunohistochemical studies. A review of the literature on retroperitoneal
      schwannoma is included.

PMID- 8283541
TI  - Ileal conduit venous varices from portal hypertension as a cause of recurrent,
      massive hemorrhage: case report and review of the literature.
AB  - Variceal bleeding from an ileal conduit stoma is an uncommon complication of
      portal venous hypertension. We report on a 59-year-old man who experienced
      frequent and severe bleeding episodes from the parastomal skin and mucosa of an
      ileal conduit requiring multiple blood transfusions. A mesenteric angiogram
      showed portal hypertension and large varices around the ileal conduit. Resolution
      of the dilated cutaneous veins occurred after a portosystemic shunt and he has
      had no further bleeding episodes. Recognition of this unusual complication of
      ileostomy formation is important for urological surgeons who may encounter
      patients with liver disease requiring urinary diversion.

PMID- 8283542
TI  - Embolization to control iatrogenic ureteral hemorrhage: a case report.
AB  - Gross hematuria following percutaneous or endourological intervention is well
      known and widely documented. We report an unusual case of angiographically
      documented hemorrhage from a ureteral branch that was injured by cystoscopic
      removal of a Double-J  stent, and subsequent successful transcatheter
      embolization. This case demonstrates the important role of angiographic diagnosis
      and therapy in the management of iatrogenic hemorrhage.

PMID- 8283543
TI  - Bladder necrosis secondary to pelvic artery embolization: case report and
      literature review.
AB  - Bladder necrosis is a rare entity in the urological literature. We report a case
      of bladder necrosis secondary to pelvic artery embolization to control
      intractable hemorrhage from a pelvic fracture.

PMID- 8283544
TI  - The Alcock syndrome: temporary penile insensitivity due to compression of the
      pudendal nerve within the Alcock canal.
AB  - Penile insensitivity is a symptom commonly observed after traumatic or iatrogenic
      nerve lesions, or in association with neurological or vascular diseases. In
      contrast, we report 2 cases of intermittent genital hypesthesia that occurred in
      cyclists after long-term bicycle riding. Anatomical studies show that this
      condition was probably caused by an irritation of the pudendal nerve during its
      course through the Alcock canal as reported in the literature. No pathological
      findings were demonstrated on extensive physical examinations, medical history
      and all medical imagings (sonography of abdomen, prostate and testes, and
      magnetic resonance imaging of the pelvis and lumbar spine) as well as
      radiodiagnostics and Doppler sonography, nor was there evidence of other
      neurological disturbances. The symptoms in the 2 patients spontaneously resolved
      after 4 and 7 weeks, respectively, without specific medical therapy.

PMID- 8283545
TI  - High flow priapism after blunt perineal trauma: resolution with bucrylate
      embolization.
AB  - We report on 2 patients (ages 21 and 33 years) with high flow priapism secondary
      to arteriocavernous fistula produced by perineal injury. Both cases were
      satisfactorily resolved by super-selective embolization of the fistula with
      bucrylate. Diagnosis was based on the results of gasometry in cavernous blood,
      color Doppler ultrasound and arteriography. Erectile function after 24 and 30
      months of treatment, respectively, was normal in both patients. Review of the
      literature revealed that only 13 patients have been managed with arterial
      embolization. To our knowledge our report represents the first in which
      intracavernous bucrylate embolization produced detumescence with preservation of
      erectile function.

PMID- 8283546
TI  - Complication of penile injection of autologous fat.
AB  - A new penile enlargement procedure using injection of autologous fat obtained by
      liposuction has been publicized by the media. We report on a 36-year-old man who
      suffered 2 painful inflammatory nodules requiring surgical excision 3 months
      after undergoing this new penile enlargement procedure.

PMID- 8283547
TI  - Recurrent episodes of acute scrotum with ischemic testicular necrosis in a
      patient with familial Mediterranean fever.
AB  - The tunica vaginalis is 1 of the sites involved in the recurrent febrile attacks
      of serositis, which are the hallmark of familial Mediterranean fever. The attacks
      present clinically as "orchitis." We report on a patient with familial
      Mediterranean fever in whom recurrent episodes of scrotal attacks were
      complicated by testicular necrosis requiring orchiectomy. The case emphasizes the
      challenge of recognizing and differentiating these attacks from other causes of
      acute scrotum.

PMID- 8283548
TI  - Fatal air embolism during radical retropubic prostatectomy.
AB  - Air embolism during urological surgery only rarely has been reported. We report a
      case of fatal air embolism occurring during radical retropubic prostatectomy.
      This entity is discussed in an attempt to raise the level of awareness of this
      rare but potentially lethal complication, especially in view of the ever
      increasing popularity of radical retropubic prostatectomy as the treatment for
      organ confined carcinoma of the prostate.

PMID- 8283549
TI  - Re: Control of the deep dorsal venous complex in radical retropubic
      prostatectomy.

PMID- 8283550
TI  - Re: Is tumor volume an independent predictor of progression following radical
      prostatectomy? A multivariate analysis of 185 clinical stage B adenocarcinomas of
      the prostate with 5 years of followup.

PMID- 8283551
TI  - Re: Prostate biopsy in patients after proctectomy.

PMID- 8283552
TI  - Re: Deferred treatment of low grade stage T3 prostate cancer without distant
      metastases.

PMID- 8283553
TI  - Effect of furosemide and intravenous normal saline fluid load upon the renal
      resistive index in nonobstructed kidneys in children.
AB  - Recent literature has shown that relative to baseline the renal resistive index
      remains unchanged in nonobstructed kidneys and increases in obstructed kidneys
      after administration of furosemide. To our knowledge the effect upon the renal
      resistive index of furosemide administered in conjunction with intravenous normal
      saline fluid load has not been reported. We evaluated the renal resistive index
      in 13 nonobstructed kidneys in 8 children 6 to 18 years old before and after
      furosemide and intravenous normal saline fluid load. The mean resistive index
      decreased from baseline (mean decrease was 0.06 +/- 0.06 standard deviation),
      with the observation of a resistive index decrease significant to p < 0.005). It
      appears likely that the combination of an intravenous normal saline fluid load
      and furosemide caused the resistive index decrease, since a decrease was not
      observed with furosemide alone; however, these results cannot exclude the
      possibility that the resistive index decrease was due to the intravenous normal
      saline fluid load alone. Nonetheless, these data are important since they may
      provide the foundation for the development of a pharmacologically challenged
      Doppler sonographic examination using furosemide and intravenous normal saline
      fluid load to evaluate better potentially obstructed kidneys.

PMID- 8283554
TI  - Urinary levels of the renal tubular enzyme N-acetyl-beta-D-glucosaminidase in
      unilateral obstructive uropathy.
AB  - Elevated urinary levels of the renal tubular enzyme, N-acetyl-beta-D
      glucosaminidase (NAG), have been shown to be associated with reversible tubular
      damage and, therefore, may serve as an indicator of tubular damage in the setting
      of presumed obstruction uropathy. This study compares urinary NAG levels in
      children with apparent upper tract obstruction with normal children to assess the
      sensitivity of this assay for the detection of possible renal tubular damage. The
      study included 40 children 3 weeks to 16 years old with unilateral ureteropelvic
      junction obstruction (30) or primary obstructive megaureter (10). Urine was
      obtained from the bladder in all children and from the renal pelvis or ureter in
      30 patients at surgery. Pelvic and ureteral urinary NAG levels were consistently
      higher than bladder levels. In patients with ureteropelvic junction obstruction
      NAG levels were 7 times higher than normal (76 units per mg., p < 0.0001) and 3
      times higher than normal in patients with obstructive megaureter (29 units per
      mg., p < 0.001). The mean bladder urinary NAG levels in patients with
      ureteropelvic junction obstruction (17.6 units per mg. creatinine, standard error
      of mean 2.01, p < 0.001) and megaureters (19.2 units per mg. creatinine, standard
      error of mean 3.6, p < 0.049) were elevated above control patients (10.6 units
      per mg. creatinine, standard error of mean 1.02). Elevated urinary NAG levels in
      the renal pelvis, ureter and bladder may be helpful in identifying upper tract
      obstruction, which if left untreated, might cause progressive renal
      deterioration.

PMID- 8283555
TI  - Positive bladder cooling test in neurologically normal young children.
AB  - The bladder cooling test, which consists of rapid infusion of 0 to 8C saline into
      the bladder with simultaneous pressure measurement, was performed in 50
      neurologically intact infants and children 6 months to 13 years old. The patients
      were referred for urodynamic investigation because of various disorders of the
      lower urinary tract. A positive bladder cooling test was defined as a sustained
      reflex detrusor contraction of about the same magnitude as the micturition
      contraction. The test was positive during the first 4 years of life but typically
      negative in children older than 5 years. These findings indicate that a positive
      bladder cooling test is an infant reflex response that, with the maturation of
      the central nervous system, becomes suppressed by descending signals from higher
      centers.

PMID- 8283556
TI  - Magnetic resonance imaging of pelvic tumors in children.
AB  - Pelvic tumors in children may be large, complex and of unknown origin.
      Preoperative radiological information regarding tumor localization and extent
      becomes essential in these cases for proper staging and surgical planning.
      Magnetic resonance imaging (MRI) offers the ability to enhance the surgical
      preparation of children who present with a pelvic mass. Advantages of MRI over
      computerized tomography include improved soft tissue characterization, signal
      enhancement of neuroendocrine tumors and multiplanar imaging. These features
      better define the origin, size and extent of tumors. In addition, no ionizing
      radiation is required. Several examples of pelvic tumors are presented. The new
      anatomical information provided by MRI altered surgical planning previously based
      on computerized tomography findings alone.

PMID- 8283557
TI  - Reconstruction of the umbilicus in exstrophy.
AB  - Reconstruction of the umbilicus has cosmetic and functional value in the surgical
      treatment of the child with bladder exstrophy. We report on 12 patients who
      underwent creation of a neoumbilicus as part of genitourinary reconstruction.

PMID- 8283558
TI  - Covered exstrophy and visceral sequestration with complete double bladder.
AB  - A 13-year-old boy had a complete double bladder and urethra associated with an
      inferior abdominal lesion, which on histological examination proved to be a
      colonic remnant with no communication to the underlying bowel. This entity is one
      of the exstrophy/epispadias complex variants known as covered exstrophy with
      sequestered bowel. Although 4 cases of this anomaly have been reported in the
      literature, to my knowledge this is the first such case with a double bladder.
      Excision of the lesion and the incontinent bladder was performed, and the ureter
      was reimplanted in the contralateral continent bladder.

PMID- 8283559
TI  - Cantwell-Ransley epispadias repair in male epispadias and bladder exstrophy.
AB  - A total of 16 boys (8 with primary epispadias and 8 with bladder exstrophy)
      underwent epispadias reconstruction as a 1-stage procedure. Reverse meatal
      advancement of MAGPI, ventral transposition of the neourethra and chordee
      correction by corporeal rotation or "cavernocavernostomy" were performed as
      primary (13 boys) or secondary/salvage (3 boys) procedures. At a mean followup of
      27 months all children had a horizontal or downward angled penis while standing.
      Catheterization in 10 children revealed an easily negotiable neourethral channel.
      Minor revision surgery was necessary in the area of previous paraexstrophy flaps
      in 2 cases, and 1 child required neourethral tapering and proximal anastomotic
      revision. The Cantwell-Ransley epispadias repair produces a good functional and
      cosmetic result.

PMID- 8283560
TI  - A dose titration, and an open 6-week efficacy and safety study of desmopressin
      tablets in the management of nocturnal enuresis.
AB  - The efficacy and safety of 6 weeks of treatment with desmopressin tablets at
      doses of 200 to 400 micrograms.at bedtime were investigated in 33 children with
      monosymptomatic nocturnal enuresis. During an initial 1 to 2-week dose titration
      period 22 patients (67%) became either completely dry or showed improvement, 7
      (21%) showed no response and 4 (12%) dropped out of therapy. During tablet
      treatment 17 patients on 400 micrograms.and 5 on 200 micrograms.at bedtime
      increased the number of weekly dry nights from 2.0 +/- 1.6 (standard deviation)
      during a 2-week observation period to 5.2 +/- 1.9 (p < 0.001). During a
      subsequent 2-week period 40 micrograms.intranasal desmopressin showed a similar
      overall efficacy, with a mean of 5.4 +/- 1.6 dry nights per week. In addition,
      intranasal treatment was able to increase the number of dry nights in 2 of the 7
      nonresponders to tablet treatment.

PMID- 8283561
TI  - Tubularized, incised plate urethroplasty for distal hypospadias.
AB  - A technique is described for correction of distal hypospadias with minimal
      chordee by tubularizing the urethral plate. The key step is deep longitudinal
      incision of the plate, which allows for tubularization without the need for
      additional flaps. The resultant neourethra is functionally adequate and an
      excellent cosmetic result with a vertically oriented meatus is achieved. A total
      of 16 boys underwent the procedure with no case of meatal stenosis or fistula
      occurring during a median followup of 22 months.

PMID- 8283562
TI  - Extensive mobilization of the urethral plate and urethra for repair of
      hypospadias: the modified Barcat technique.
AB  - The modified Barcat technique was used to treat 168 patients with hypospadias
      during the last 5 years. The technique, which is applicable for distal
      hypospadias, uses apposing fully mobilized meatal based skin flaps. Cosmetic and
      functional results are excellent, with only 3.5% of the patients requiring
      reoperation. Because the surgical technique does not depend on the configuration
      of the glans, depth of the urethral groove, caliber of the urethral meatus or
      even whether the patient has been circumcised, it is particularly suitable for
      training residents who can perform a single operation to correct a wide variety
      of cosmetic deformities.

PMID- 8283563
TI  - Repair of hypospadias complications using the meatal based flap urethroplasty.
AB  - While long used for primary hypospadias repair, meatal based flap urethroplasty
      has not been widely considered a viable alternative for a secondary procedure. We
      reviewed 200 patients who underwent meatal based flap urethroplasty and
      identified 9 (4.5%) who underwent the procedure for correction of complications
      of previous hypospadias repair, including urethrocutaneous fistula, severe meatal
      retraction, persistent chordee and hair in the urethra. The complication was
      corrected with a single operation in 8 of the 9 patients (89%). A single small
      fistula developed in 3 patients, which closed spontaneously in 2 and required
      another procedure in 1. Meatal based flap urethroplasty should be considered for
      correction of distal complications of hypospadias repair.

PMID- 8283564
TI  - Perineal lipoma and the accessory labioscrotal fold: an etiological relationship.
AB  - Congenital scrotal disorders are unusual, including penoscrotal transposition,
      bifid scrotum, ectopic scrotum and accessory scrotum. The latter 2 entities are
      extremely rare. Because accessory scrota usually arise in the absence of
      associated anomalies, an etiology has been enigmatic. We present 2 cases of
      accessory labioscrotal folds, including a female patient. An exhaustive
      literature review allowed comparison with all reported cases (23) and showed a
      frequent association with perineal lipoma (83%). On that basis, we were able to
      classify accessory labioscrotal folds into 2 types and recommend a different
      course of management for each. Accessory labioscrotal folds usually develop when
      intervening mesenchymal tissue disrupts the continuity of the caudally developing
      labioscrotal swelling.

PMID- 8283565
TI  - Comparison of urinary bladder function in rats with hereditary diabetes
      insipidus, streptozotocin-induced diabetes mellitus, and nondiabetic osmotic
      diuresis.
AB  - In vivo and in vitro bladder function were studied in three different models of
      increased diuresis: 1) Brattleboro rats with hereditary diabetes insipidus
      (di/di), 2) Sprague-Dawley rats with streptozotocin-induced diabetes mellitus
      (STZ), and 3) Sprague-Dawley rats with increased diuresis due to 5% sucrose added
      to the drinking water. When compared with controls, all three models showed
      bladder mass, increased water consumption and urine output, higher mean and
      maximal increased micturition volumes, and greater bladder capacity and
      compliance by in vitro cystometry. The changes were more extensive in di/di rats
      than in the STZ and sucrose-drinking rats. The concentration of bladder collagen
      decreased in all three rat models when compared with controls. However, the
      collagen concentration of STZ bladders was significantly lower than the collagen
      concentration of di/di and sucrose bladders, suggesting that the decrease in
      bladder collagen concentration associated with experimental diabetes mellitus is
      only partly related to the increased diuresis. Contractile function was studied
      using a whole bladder model. Responses of whole bladders from control and
      diabetic rats to electrical field stimulation, carbachol and KCl were identical.
      Volume-pressure relations of the isolated whole bladder showed that the magnitude
      of the contractile response to KCl is constant at intravesical volumes ranging
      from about 10 to 95% of cytometrical bladder capacity. Bladders from Brattleboro
      di/di rats and STZ rats showed a rightward shift of volume-passive pressure
      curves when compared with appropriate controls. Bladders from sucrose-drinking
      rats had volume-passive pressure curves similar to the bladders from controls.
      This study suggests that while contractile function remains intact with increased
      diuresis, the passive function changes, with the bladder becoming more
      distensible.

PMID- 8283566
TI  - Preliminary results of laser tissue welding in extravesical reimplantation of the
      ureters.
AB  - One exciting potential use of laparoscopic technology is the extravesical
      reimplantation of the ureters. We have assessed the efficacy of laser-activated
      fibrinogen solder to close vesical muscle flaps over submucosal ureters (Lich
      Gregoir technique) in a canine model. Four dogs were subjected to unilateral flap
      closures via a protein solder (indocyanine green and fibrinogen) applied to the
      bladder serosa and exposed to 808 nm. continuous wave diode laser energy.
      Contralateral reimplantation was performed using 4-zero vicryl muscle flap
      closures (controls). At 7, 14 and 28 days postoperatively, intravenous pyelograms
      confirmed bilateral ureteral patency. At intravesical pressures above 100 cm.
      H2O, there was no evidence of wound disruption in either group. Nondisrupted
      wound closures were sectioned and strained until ultimate breakage to determine
      tensile strength. At each study interval the laser-welded closures withstood
      greater stress than the controls. Although these data represent single tissue
      samples and are not amenable to statistical analysis, laser-welded closures
      appeared to be stronger at each study interval. In conclusion, laser-welded
      vesical wound closures appear at least as strong as suture closures in the canine
      model.

PMID- 8283567
TI  - A clone by any other name is still an ethical concern.

PMID- 8283568
TI  - Pro-free enterprise group challenges FDA's authority to regulate drug companies'
      speech.

PMID- 8283569
TI  - From the Centers for Disease Control and Prevention. Influenza activity--United
      States, 1993-94 season.

PMID- 8283570
TI  - From the Centers for Disease Control and Prevention. Outbreaks of Mycoplasma
      pneumoniae respiratory infection--Ohio, Texas, and New York, 1993.

PMID- 8283571
TI  - From the Centers for Disease Control and Prevention. Update: respiratory
      syncytial virus activity--United States, 1993.

PMID- 8283572
TI  - From the Centers for Disease Control and Prevention. Resurgence of pertussis-
      United States, 1993.

PMID- 8283573
TI  - From the Centers for Disease Control and Prevention. Performance evaluation
      program for Mycobacterium tuberculosis drug-susceptibility testing process.

PMID- 8283574
TI  - Hyponatremic encephalopathy after endometrial ablation.

PMID- 8283575
TI  - Hyponatremic encephalopathy after endometrial ablation.

PMID- 8283576
TI  - Hyponatremic encephalopathy after endometrial ablation.

PMID- 8283577
TI  - Hyponatremic encephalopathy after endometrial ablation.

PMID- 8283578
TI  - Hyponatremic encephalopathy after endometrial ablation.

PMID- 8283579
TI  - CEA for monitoring colon cancer.

PMID- 8283580
TI  - CEA for monitoring colon cancer.

PMID- 8283581
TI  - CEA for monitoring colon cancer.

PMID- 8283582
TI  - Use of anabolic-androgenic steroids: we are talking prevalence rates.

PMID- 8283583
TI  - Use of anabolic-androgenic steroids: we are talking prevalence rates.

PMID- 8283584
TI  - Malaria therapy for neurosyphilis.

PMID- 8283585
TI  - Changes in antipsychotic drug use in nursing homes during implementation of the
      OBRA-87 regulations.
AB  - OBJECTIVES: To describe the changes in antipsychotic drug use in nursing homes
      during the period surrounding the implementation of federal legislation designed
      to reduce unnecessary use (the Omnibus Budget Reconciliation Act of 1987 [OBRA
      87]) and to identify nursing home characteristics associated with such changes.
      DESIGN: Longitudinal study of 9432 Tennessee Medicaid enrollees 65 years of age
      or older who continuously resided in Tennessee from April 1, 1989, to September
      30, 1991, a 30-month period surrounding implementation of OBRA-87. MAIN OUTCOME
      MEASURES: Changes in the use of antipsychotic and other psychotropic drugs.
      RESULTS: During the 30-month period, antipsychotic drug use decreased from 23.9
      to 17.5 days per 100 days of residence, a 26.7% decline (P < .001), which
      resulted from both a decrease in new users (P < .001) and a reduction in long
      term use of antipsychotic drugs (P < .001). There was no concomitant increase in
      other psychotropic drug use. A multivariate analysis revealed that changes in
      antipsychotic use were strongly associated with baseline antipsychotic use (P =
      .001) and third-shift staffing levels (P = .003). Nursing homes with baseline
      antipsychotic drug use and third-shift staffing above the median reduced
      antipsychotic drug use by 41%, compared with a 2% increase in nursing homes where
      both of these factors were below the median (P < .0001). CONCLUSIONS: A
      substantial decrease in antipsychotic drug use coincided with the implementation
      of OBRA-87. Although this decrease is consistent with an improvement in quality
      of nursing home care, further research is needed to determine the effects of this
      legislation on resident outcomes.

PMID- 8283586
TI  - Chronic sinusitis. Relationship of computed tomographic findings to allergy,
      asthma, and eosinophilia.
AB  - OBJECTIVE: To develop a technique for evaluating the severity of chronic sinus
      disease and to examine the correlation with allergy, asthma, and eosinophilia.
      DESIGN: A survey of 104 patients undergoing surgery for chronic sinusitis.
      SETTING: A university hospital ear, nose, and throat clinic. PATIENTS: A referral
      population of adult patients being scheduled for endoscopic sinus surgery was
      eligible; 104 completed questionnaires and agreed to participate. MAIN OUTCOME
      MEASURES: Computed tomographic scans were reviewed and scored for extent of
      disease. Serum samples were assayed for total IgE and specific IgE antibodies to
      common inhalant allergens. Peripheral blood samples were analyzed for total
      eosinophil count. Surgical biopsy specimens were examined for eosinophilia and
      cultured for bacteria and fungi. RESULTS: Extensive disease was present in 39% of
      subjects and correlated well with asthma, specific IgE antibodies, and
      eosinophilia, but not with elevated total IgE. Among patients with peripheral
      eosinophilia, 87% had extensive disease. All cultures grew aerobic bacteria;
      anaerobes and fungi were uncommon. CONCLUSIONS: We present a system for
      quantitation of disease extent using computed tomographic scans of patients with
      chronic sinusitis. The well-accepted associations of chronic sinusitis with
      asthma and allergy appear to be restricted to the group with extensive disease.
      The presence of peripheral eosinophilia in patients with sinusitis indicates a
      high likelihood of extensive disease.

PMID- 8283587
TI  - Cost-effectiveness of a routine varicella vaccination program for US children.
AB  - OBJECTIVE: To evaluate the economic consequences of a routine varicella
      vaccination program that targets healthy children. METHODS: Decision analysis was
      used to compare the costs, outcomes, and cost-effectiveness of a routine
      vaccination program with no intervention. Clinical outcomes were based on a
      mathematical model of vaccine efficacy that relied on published and unpublished
      data and on expert opinion. Medical utilization rates and costs were collected
      from multiple sources, including the Kaiser Permanente Medical Care Program and
      the California Hospital Discharge Database. RESULTS: A routine varicella
      vaccination program for healthy children would prevent 94% of all potential cases
      of chickenpox, provided the vaccination coverage rate is 97% at school entry. It
      would cost approximately $162 million annually if one dose of vaccine per child
      were recommended at a cost of $35 per dose. From the societal perspective, which
      includes work-loss costs as well as medical costs, the program would save more
      than $5 for every dollar invested in vaccination. However, from the health care
      payer's perspective (medical costs only), the program would cost approximately $2
      per chickenpox case prevented, or $2500 per life-year saved. The medical cost of
      disease prevention was sensitive to the vaccination coverage rate and vaccine
      price but was relatively insensitive to assumptions about vaccine efficacy within
      plausible ranges. An additional program for catch-up vaccination of 12-year-olds
      would have high incremental costs if the vaccination coverage rate of children of
      preschool age were 97%, but would result in net savings at a coverage rate of
      50%. CONCLUSIONS: A routine varicella vaccination program for healthy children
      would result in net savings from the societal perspective, which includes work
      loss costs as well as medical costs. Compared with other prevention programs, it
      would also be relatively cost-effective from the health care payer's perspective.

PMID- 8283588
TI  - The rational clinical examination. Does this dizzy patient have a serious form of
      vertigo?

PMID- 8283589
TI  - Users' guides to the medical literature. III. How to use an article about a
      diagnostic test. A. Are the results of the study valid? Evidence-Based Medicine
      Working Group.

PMID- 8283590
TI  - Changing physician prescribing practices. Regulation vs education.

PMID- 8283591
TI  - Medical student voices.

PMID- 8283592
TI  - Who cares?

PMID- 8283593
TI  - Rupture of the uterus.

PMID- 8283594
TI  - Rupture of the uterus in full-term pregnancy.
AB  - Of 48,519 deliveries conducted at Jinnah Postgraduate Medical Centre (JPMC) over
      7 years (January, 1986 to December, 1992), 257 were of ruptured uterus, giving a
      rate of one in 189 deliveries. Main cause of rupture was obstructed labour.
      Maternal mortality was 3.9% and foetal mortality 88% in cases admitted with
      uterine rupture and 17.6% in rupture occurring within the hospital (JPMA 43: 172,
      1993).

PMID- 8283595
TI  - Rupture of the uterus.
AB  - Fifty cases of uterine rupture were managed in 4 years giving a frequency of 1
      per 89.9 deliveries. There was an obvious difference between those with a
      previously scarred uterus (34) vs those without a scar (16) cephalopelvic
      disproportion, grand multiparity and mismanagement of cases by traditional birth
      attendant (TBAs) were the common etiologic factors in the unscarred uterus,
      cephalopelvic disproportion, forceps delivery, grand multiparity and prolonged
      first stage of labour were the common etiologic factors in patients with
      previously scarred uterus. In the unscarred group both maternal and foetal
      (81.6%) mortality was high (JPMA 43: 174, 1993).

PMID- 8283596
TI  - Association of upper gastrointestinal lesions with addictions.
AB  - The association of upper gastrointestinal (G.I.) lesions with various addictions
      was studied in 383 consecutive patients endoscoped over a year. Of the total, 179
      (47%) had no addictions and 204 (53%) were addicted to either cigarette smoking
      (70%), tobacco chewing with pan (23%), pan alone (5%) or alcohol (2%). Overall,
      78% cases with and 59% without addictions had an upper G.I. lesion on endoscopy
      (P < 0.001). Duodenal ulcer was commonest lesion in all types of addiction.

PMID- 8283597
TI  - Epidemiology of salmonellosis and its sensitivity in Karachi.
AB  - Over the past five years 25,000 blood cultures were screened for septicaemia. Of
      these 6.7% were positive for salmonella species, the commonest being salmonella
      typhi accounting for 92% of total salmonella isolates. Over the years, S. typhi
      showed a gradual decline ranging from 96.7 to 87%. While salmonella paratyphi A
      has shown a gradual increase ranging from 2.5% to 11.4%. Salmonellosis peaked in
      the year 1990 suggesting an epidemic. The antibiotic sensitivity pattern showed a
      gradual increase in resistance over the years and even resistance to the new
      quinolones has emerged. Thus salmonellosis poses a major threat to the community
      and we must look into the alternative antibiotics to combat the threat.

PMID- 8283598
TI  - Carbon monoxide fractions in cigarette and hookah (hubble bubble) smoke.
AB  - We studied the carbon monoxide (CO) fractions in hookah and cigarette smoke,
      using a carbon monoxide micro smokerlyzer (model EC50, BEDFONT, U.K.). Mean
      carbon monoxide fractions (% by volume) of hookah smoke, using domestic charcoal
      were 0.38 +/- 0.07 (large hookah; unfiltered); 1.40 +/- 0.43 (small hookah;
      unfiltered); 0.34 +/- 0.06 (large hookah; filtered); 1.36 +/- 0.35 (small hookah;
      filtered) and 0.41 +/- 0.08 (cigarette smoke). The highest fractions were
      obtained with small size hookah and increase in size of hookah (i.e., volume of
      air in water base, fire bowl volume, pipe length, etc.) reduced the CO fraction
      significantly (P < 0.001). The fractions of cigarette lie between large and small
      hookah. The fractions vary slightly with different varieties of tobacco, e.g., CO
      fractions with Dera wala tobacco are significantly low (P < 0.05). Use of
      commercial charcoal gives significant rise in CO fractions (P < 0.001).
      Comparison of filtered and unfiltered smoke shows no significant difference in
      values. We conclude that the CO hazard is as high with hookah smoking as with
      cigarette smoking.

PMID- 8283599
TI  - Phyllocontin (theophylline) induced esophagitis.

PMID- 8283600
TI  - Sweet's syndrome.

PMID- 8283601
TI  - Antibacterial properties of an egg.

PMID- 8283602
TI  - Stroke--modern management.

PMID- 8283603
TI  - Comparison of adenosine and treadmill exercise thallium-201 stress tests for the
      detection of coronary artery disease.
AB  - To determine the clinical usefulness of adenosine Tl-201 imaging for the
      evaluation of coronary artery disease, 22 patients with suspected coronary artery
      disease who underwent adenosine and exercise Tl-201 single photon emission
      computed tomography (SPECT) were studied. The peak levels of heart rate (83 vs
      123 bpm, p < 0.001), systolic blood pressure (124 vs 164 mmHg, p < 0.001),
      diastolic blood pressure (70 vs 86 mmHg, p < 0.01) and rate pressure products
      (10220 vs 20410 bpm x mmHg, p < 0.001) were markedly smaller during adenosine
      infusion than during exercise. Segmental agreements between adenosine and
      exercise tests were 90% (218 of 242 segments) regarding the presence of perfusion
      defects and 89% (215 of 242 segments) regarding the presence of redistribution.
      Regional Tl-201 uptake (r = 0.85, p < 0.001) and the extent (r = 0.75, p < 0.001)
      and intensity (r = 0.83, p < 0.001) of Tl-201 defects during adenosine testing
      were closely correlated with those of exercise testing. Adenosine and exercise
      tests showed similar sensitivities for the identification of individual coronary
      stenosis (85% vs 78%). However, in patients who were unable to perform adequate
      exercise (maximal heart rate < 120 bpm), the sensitivity of adenosine imaging
      tended to be higher than that of exercise imaging (92% vs 69%, p = 0.07).
      Adenosine Tl-201 imaging is an alternative to the exercise test for assessing the
      severity and loci of coronary artery disease, especially in patients who are
      unable to perform adequate physical exercise.

PMID- 8283605
TI  - Relationship between blood pressure and heart rate while awake and asleep in
      patients with mild essential hypertension.
AB  - Blood pressure (BP) and heart rate (HR) (BP waveforms) are affected by external
      stress during waking and BP is reduced to its lowest level (base BP) during
      sleep. This study investigated the relationship between BP waveforms while awake
      and base BP waveforms during sleep. The intra-arterial BPs of 64 inpatients (34
      males and 30 females, age: 42 +/- 11, mean +/- SD) with mild essential
      hypertension were measured for 24 h by the telemetry method. The average ln
      (SBP/DBP) (m) while awake and the m at base BP (ln: natural logarithm, SBP:
      systolic BP, DBP: diastolic BP) had approximately the same values in each patient
      (mean difference: -0.02 +/- 0.07). The product of the RR interval (60/HR) and DBP
      (RR x DBP) while awake and at base BP had almost the same value (mean difference:
      -3.2 +/- 10 mmHg.sec). According to the Windkessel model, the RR interval during
      which blood-flow volume in relation to the m value is at its highest can be
      inferred as S (em-1)/(em-m-1) (S: systolic time). Using this formula, we
      developed a formula to estimate base RR from waking m, BP, and RR. Calculations
      with this estimate formula produced a very slight difference (0.0 +/- 0.1 sec)
      between estimated and actual values for base RR. For the most part, it was
      possible to infer the base DBP value from the estimated base RR using RR x DBP
      while awake (mean difference: -3.7 +/- 7.0 mmHg). These results suggest that the
      base BP waveform may be the most efficient pattern, and that waking BP waveforms
      change based on the base BP waveform during sleep.

PMID- 8283604
TI  - Insulin-like growth factor I receptors in human cardiac myocytes and their
      relation to myocardial hypertrophy.
AB  - Specific binding sites for insulin-like growth factor I (IGF-I) and their
      expression during cardiac myocyte hypertrophy were studied by autoradiographic
      analysis of right ventricular biopsy specimens from patients with hypertrophic
      cardiomyopathy (9 cases), dilated cardiomyopathy (8 cases), and sick sinus
      syndrome (5 cases). Frozen specimens were cut into 5 microns-thick sections and
      thaw-mounted on albumin-coated slides. After incubation with [125I]IGF-I, with or
      without excess cold IGF-I, autoradiography was performed, and grains over
      myocytes were counted microscopically. Binding of [125I]IGF-I was inhibited in a
      dose-dependent manner by unlabeled IGF-I and competed for by IGF-I > IGF-II >
      insulin. The maximal grain density was higher in hypertrophic cardiomyopathy (186
      +/- 47/1.8 x 10(-2) mm2) than in dilated cardiomyopathy (124 +/- 13/1.8 x 10(-2)
      mm2) or sick sinus syndrome (98 +/- 18/1.8 x 10(-2) mm2) (p < 0.01). There was a
      strong correlation between the maximal grain density and the diameter of right
      ventricular myocytes in hypertrophic cardiomyopathy (r = 0.83), but no similar
      correlation was observed in dilated cardiomyopathy or sick sinus syndrome. These
      data suggest that IGF-I receptors are present in adult human cardiac myocytes,
      and that IGF-I receptors are related to the development of myocyte hypertrophy in
      hypertrophic cardiomyopathy.

PMID- 8283606
TI  - The short- and long-term prognosis for acute myocardial infarction after
      emergency coronary angioplasty.
AB  - The short- and long-term prognosis for acute myocardial infarction after
      reperfusion was examined in 175 patients with successful emergency angioplasty
      and in 29 failed cases. During hospitalization, more cardiac events occurred in
      the failed group than in the successful group (58.6% versus 12.6%; p < 0.001),
      especially cardiac death and coronary bypass surgery (27.6% versus 4.0%, and
      41.4% versus 4.6%; p < 0.001, respectively). The only difference found in the
      incidence of post-discharge cardiac events was a higher frequency of cardiac
      death in the failed group (9.5% versus 1.2%; p < 0.02). The failed group also had
      a lower cumulative survival rate at 5 years (69.0% versus 95.3%; p < 0.01). Cox
      proportional hazard analysis showed that the results of angioplasty, cardiac
      index, peak creatine kinase level, and the number of diseased vessels were
      significant independent variables for the prediction of subsequent cardiac death
      at long-term follow-up. Thus, successful reperfusion by emergency angioplasty
      improved the prognosis of acute myocardial infarction, even when other important
      variables were considered.

PMID- 8283607
TI  - Auto-antibody against adenine nucleotide translocator in dilated cardiomyopathy
      and myocarditis--incidence and relation to cardiac function and morphology.
AB  - Using an enzyme-linked immunosorbent assay, we measured anti-adenine nucleotide
      translocater (ANT) antibody in control subjects and in patients with dilated
      cardiomyopathy (DCM), myocarditis, and other heart disease. Analysis with sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and
      immunoabsorption tests confirmed accurate purification of the ANT protein and
      correct measurement of anti-ANT auto-antibody. Anti-ANT antibody was detected in
      6 of 37 cases (16%) of DCM and in 5 of 12 cases (42%) of myocarditis. This
      antibody was not positive in other heart diseases or in apparently healthy
      controls. There were no differences between anti-ANT autoantibody-positive and 
      negative DCM or myocarditis patients in any of the cardiac parameters examined
      (left ventricular ejection fraction, LVEF; left ventricular end-diastolic
      dimension, LVDd; and cardiothoracic ratio, CTR). Moreover, in patients who were
      positive for anti-ANT auto-antibody, no positive correlations were found between
      the parameters and anti-ANT antibody titers in either DCM or myocarditis.
      Although these results indicate that the detection of anti-ANT antibody was
      achieved at a high specificity and could have certain diagnostic value in DCM and
      myocarditis, there was no statistically significant relationship between the
      cardiac parameters (LVEF, LVDd, and CTR) and anti-ANT antibody titers in either
      DCM or myocarditis. Some compensatory mechanism of ventricular function may mask
      the effects of the anti-ANT auto-antibody or alternatively, this auto-antibody
      may have mimic effects on the pathogenesis and/or progression of DCM and
      myocarditis.

PMID- 8283608
TI  - Role of nitric oxide in the vasodilatory responses to acetylcholine and
      bradykinin in perfused hearts.
AB  - The role of nitric oxide in the coronary vasodilation caused by acetylcholine or
      bradykinin in perfused guinea-pig hearts was investigated by using 1 mM L-NG
      nitro arginine (L-NNA), a specific inhibitor of the formation of nitric oxide
      from L-arginine. L-NNA increased coronary perfusion pressure and inhibited the
      vasodilator responses to acetylcholine and bradykinin. The extent of vasodilation
      was evaluated in terms of the reduction of perfusion pressure from the initial
      baseline that had been induced by U-46619. L-NNA markedly attenuated coronary
      vasodilation caused by 5 x 10(-11) mol of acetylcholine from 15 +/- 1 to 4 +/- 1
      mmHg (p < 0.01), and that caused by 1 x 10(-11) mol bradykinin from 21 +/- 2 to 8
      +2- 1 mmHg (p < 0.01). On the other hand, L-NNA only weakly inhibited coronary
      vasodilation caused by 5 x 10(-7) mol of acetylcholine from 40 +/- 3 to 27 +/- 4
      mmHg (p < 0.01), and that caused by 1 x 10(-9) mol of bradykinin (from 39 +/- 2
      to 32 +/- 2 mmHg (p < 0.01). L-NNA had no effect on the vasodilation induced by 1
      x 10(-8) mol of bradykinin. Ibuprofen, cyclooxygenase inhibitor, did not affect
      these vasodilatory responses. These results suggest that the formation of nitric
      oxide from L-arginine in coronary resistance vessels helps to regulate vascular
      tone, and that prostaglandins are not related to the vasodilatory responses to
      acetylcholine or bradykinin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283609
TI  - Assessment of preload reserve in myocardial ischemia--the relation between
      preload reserve and ischemic size differs between anterior descending and
      circumflex coronary artery occlusions in a canine model.
AB  - The role of changes in preload in maintaining stable hemodynamics during coronary
      obstruction was assessed in the presence of myocardial ischemia due to occlusions
      of the left anterior descending (LAD) and left circumflex (LCX) coronary
      arteries. Changes in preload (mean left atrial pressure) to maintain a constant
      stroke volume after coronary occlusion were examined in 18 anesthetized dogs (LAD
      occlusion in 9 dogs, LCX occlusion in 9 dogs). The level of ischemia was assessed
      sonomicrometrically. Ventricular function curves relating left atrial pressure to
      stroke volume were assessed during a control state and after 1 min of coronary
      occlusion. The extent of preload reserve after coronary occlusion was examined on
      the ventricular function curves and was defined as the change in mean left atrial
      pressure required to maintain stroke volume at the level of the control state
      under conditions of regional ischemia. Ischemic size was determined by a stereo
      angiogram after the animals were sacrificed. The extent of preload reserve (X)
      was linearly related to the ischemic size (Y) in both LAD (Y = 0.90 + 0.16X, r =
      0.76, p < 0.001) and LCX (Y = -1.79 + 0.19X, r = 0.79, p < 0.001) occlusions. The
      slopes of the regression lines in LAD and LCX occlusions were the same. The X
      intercepts of these lines were -5.6% and 9.4% of the left ventricular weight in
      LAD and LCX ischemia (p < 0.001), respectively. Thus, the presence of systolic
      wall motion abnormalities due to coronary occlusion can be compensated for
      hemodynamically by changes in the preload reserve.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8283610
TI  - Attenuation of myocardial stunning by an increase in the H+ buffering capacity of
      the perfusate and that by hypoxic preperfusion are affected differently by the
      free [Ca2+] of the perfusate.
AB  - OBJECTIVES: Protons produced during ischemia may increase intracellular Na+
      (Na+i) through Na+/H+ exchange, and may lead to Ca2+ overload through Na+/Ca2+
      exchange to cause myocardial stunning. This study investigated whether an
      increase in the H+ buffering capacity of the perfusate or a reduction of H+
      production by a brief hypoxic preperfusion before ischemia would reduce
      myocardial stunning. We also investigated whether the protective effect of these
      maneuvers depends on the free [Ca2+] of the perfusate. METHODS: Isolated rat
      hearts were preperfused with oxygenated or hypoxic buffer (pH 7.4) containing 100
      mM of either sucrose or HEPES for 10 min, followed by 15 min of total ischemia
      and 30 min of reperfusion. To investigate the dependence of the effects of HEPES
      or a brief hypoxic preperfusion, the free Ca2+ concentration in the buffer was
      changed from 1.25 mM to 2.5 mM in some hearts. RESULTS: Oxygenated preperfusion
      with buffer containing HEPES and 1.25 or 2.5 mM Ca2+ improved the metabolic and
      functional recovery with a decrease in the accumulation of Na+i during ischemia
      and in 45Ca2+ uptake during reperfusion. A brief hypoxic preperfusion with 1.25
      mM Ca2+ provided a similar protective effect whereas no protective effect was
      observed when the [Ca2+] was raised to 2.5 mM. CONCLUSIONS: An increase in the H+
      buffering capacity or a brief hypoxic preperfusion reduced myocardial stunning
      with improved metabolic recovery, and reduced Ca2+ uptake. However, the effects
      of these interventions were affected differently by the free [Ca2+] of the
      perfusate, which suggests that they work, at least in part, through some
      different mechanism(s).

PMID- 8283611
TI  - Successful surgical treatment of a ruptured true postinfarction left ventricular
      aneurysm--a case report.
AB  - Rupture of a chronic postinfarction aneurysm of the left ventricle is rare and
      usually fatal. A 63-year-old man with rupture of a true left ventricular aneurysm
      67 days after myocardial infarction was treated successfully with resection of
      the aneurysm. The postoperative course was uneventful.

PMID- 8283612
TI  - About the history of the discovery of the cardiac conduction system.

PMID- 8283613
TI  - [Histology of Helicobacter pylori (Hp) infection: gastric local immunity to Hp].

PMID- 8283614
TI  - [Helicobacter pylori and gastroduodenal diseases: current status].

PMID- 8283615
TI  - [Bacteriological status, serotypes, and biotypes of Helicobacter pylori].
AB  - To divide H. pylori strains into subgroup for an etiological survey, some
      attempts have been made to determine serotypes or biotypes. A variety of
      serogroups was observed with a slide agglutination test between S. aureus
      sensitized with antisera and cells of H. pylori (Danielson et al, 1988). Three or
      more serotypes were obtained by using antisera absorbed with heterogeneous
      strains (Tanaka et al, 1990). Furthermore, the possible existence of serological
      subgroups or subtypes by ELISA was observed (Inouye et al, 1991). H. pylori
      strains were biotyped with preformed enzyme profiles (APIZYM). The strains were
      predominantly biotype II, and 4 subsets of the organisms were defined on a
      combination of motility and cytotoxin production, followed by further detailed
      types (Owen et al, 1991).

PMID- 8283616
TI  - [Lipid composition of Helicobacter pylori].
AB  - In H. pylori, we examined the composition of total lipids. In thin-layer
      chromatography, three kinds of glycolipids were detected, which were named as G
      1, G-2 and G-3. G-3 contained phosphates in addition to sugars. Total lipids
      consisted of 6.0% neutral lipids (weight %), 20.6% glycolipids (G-1, G-2) and
      73.4% phospholipids (including G-3). Total glycolipids were approximately 25% of
      total lipids. After methanolysis, cholesterol was detected in the hexane
      extractable fraction and glucose was detected by GLC in the methanol fraction
      after trimethylsilylation, in all glycolipids. Therefore, these glycolipids are
      cholesteryl glycosides. Cholesteryl glycosides are found very rarely in bacteria,
      and have been detected only in a few species of mycoplasmas and spirochetes.

PMID- 8283617
TI  - [Epidemiological studies and mode of transmission of Helicobacter pylori
      infection].
AB  - Recent epidemiological reports of Helicobacter pylori (HP) reveal that HP is
      distributed among all populations in the world. The prevalence rate in the
      developed countries is generally, lower than that in the developing countries.
      The prevalence of HP increases with age both in the developed and the developing
      countries, reflecting a socioeconomic status; the poorer a population, the
      earlier is the age of infecting HP, resulting in the higher prevalence rate of
      HP. The epidemiological evidence indicates that person-to-person transmission of
      HP may occur, through either faecal-oral or oral-oral. Gastroendoscopy
      manipulation could be one of the transmission routes. In Japan, the prevalence
      above 40 years old was as high (70-80%) as that in the developing countries,
      whereas under 40 it was as low in the developed countries. This unique mode of
      prevalence in Japan may come from an ethnic background and requires further
      studies.

PMID- 8283618
TI  - [The possibility of transendoscopic transmission of Helicobacter pylori and the
      method of disinfection of endoscopic instruments].
AB  - Although Helicobacter pylori (HP) infection has been considered to have an
      etiologic role in the development of antral gastritis and recurrence of duodenal
      ulcer, the source and normal route of transmission of HP remains unknown.
      Ironically, iatrogenic infection was the first route of transmission established.
      Through many investigations using HP DNA analysis and anti-HP antibody change,
      the possibility of transendoscopic transmission of HP has been determined. From
      the fundamental analysis of the method, by which disinfection may be sufficient
      after an usual endoscopic examination, our results suggested that on several
      occasions, HP may be transmitted even if disinfection was performed with alcohol.
      Careful cleaning of the endoscope with alkaline glutaraldehyde appears to be
      sufficient to avoid transmission of HP from one positive patient to another.

PMID- 8283620
TI  - [Experimental study in Japanese monkeys with Helicobacter pylori infection].
AB  - Japanese monkeys were studied for one month from 6 months (short-term) after
      inoculation of Helicobacter pylori, and two years (long-term). In the short-term
      study, macroscopic and histological gastritis were observed for 5 infected
      monkeys. The gastritis score, the ammonia concentration in the gastric secretion
      and the level of serum antibody (IgG) were higher for the infected group than for
      the control. In the long term study, H. pylori was always recovered for 2 years
      in the infected group, and the gastritis score was higher than the control. The
      intracellular periodic acid-Schiff (PAS) positive substances in the infected
      group decreased than that of the control. The tall of pyloric gland in the
      infected group was significantly decreased on 6 months from 1.5 years. These
      results suggest that the Japanese monkey can be used as experimental model of H.
      pylori infection and that H. pylori can induce chronic active gastritis similar
      to human.

PMID- 8283619
TI  - [Experimental infection of the cynomolgus monkey with Helicobacter pylori].
AB  - To better understand the pathogenesis of Helicobacter pylori (H. pylori)
      associated gastritis and to evaluate the effectiveness of potential therapies in
      ulcer healing, we established an experimental animal model of H. pylori
      infection. A strain of H. pylori was isolated from the stomach of a Cynomolgus
      monkey, cultured and used to inoculate as a group of H. pylori negative monkeys.
      H. pylori-induced changes in the gastric mucosa was monitored both endoscopically
      and by histological evaluation of mucosal biopsy. After inoculation, H. pylori
      was found to colonize the gastric mucosa of these primates and had induced
      gastritis. In a related experimental series, we developed an experimental acetic
      acid induced ulcer in the stomach of these monkeys. These results suggest that
      the Cynomolgus monkey may be a useful model to study H. pylori infection.

PMID- 8283621
TI  - [Experimental animal models in Mongolian gerbils and mice].
AB  - Helicobacter pylori is an emerging candidate agent for the genesis of chronic
      gastritis and peptic ulcer. There have been many challenges to establish an
      experimental infection with H. pylori in animals. In recent, several studies
      reported for animal infection with this organism. One of them was the study using
      urinary system. The study indicated the ability of H. pylori to induce
      inflammation without significant low pH condition. Experimental infection in
      Mongolian gerbils showed that H. pylori could colonize on the surface of the
      gastric mucosa in animals without human. The study of nude mice by Karita et al.
      showed several valuable facts concerning the relation between bacterial
      pathogenicity and potential of bacterial colonization in stomach. The study in
      which remaining of bacteria was extended showed that colonization of H. pylori
      was affected by bacterial flora in the stomach.

PMID- 8283622
TI  - [Adhesion of Helicobacter pylori--role of glycolipid adhesion receptors].
AB  - In the gastric mucosa, the composition of acidic glycolipids has unique feature
      of enrichment of sulfatides over gangliosides. Immunohistochemical staining using
      a monoclonal antibody demonstrated that the sulfated glycolipids specifically
      localized on surface epithelial cells. Moreover, cultured gastric mucosal cells
      actively synthesized sulfated glycolipids. We have also shown that it may be
      recognized as an adhesion receptor by Helicobacter pylori (HP). Since other
      investigators have proposed various other substances as adhesion receptors for
      HP, the mechanism of adhesion by HP might be more complex and involve several
      adhesion molecules. When given orally, sulfatides protected gastric mucosa from
      acid-ethanol induced damage. Specific localization and synthesis of sulfatides in
      the surface epithelial cells, along with their gastroprotective action, are
      reminiscent of the surface-active phospholipids which are advocated to play
      important roles in maintaining gastric mucosal hydrophobicity. Further studies
      are necessary to elucidate the physiological roles of this unique substance in
      the stomach.

PMID- 8283623
TI  - [Helicobacter pylori and urease activity--comparative study between urease
      positive and negative mutant strains].
AB  - The ammonia concentration in the gastric juice from H. pylori positive cases was
      significantly higher than that from negative cases, and there was positive
      correlation between number of H. pylori, gastritis score and ammonia
      concentration in gastric juice. It is suggested that ammonia in gastric juice
      which is produced by powerful urease activity of H. pylori is one of the
      pathogenic factors in gastritis. We succeeded in producing a urease-negative
      mutant strain of H. pylori. This strain did not colonize gastric mucosa of
      Cynomolgus monkeys. H. pylori survival time in vitro was increased at pH 2.0 in
      the presence of urea. These results suggest that urease facilitates colonization
      of gastric mucosa by H. pylori, and prolongs the survival of H. pylori in an
      acidic environment.

PMID- 8283624
TI  - [Role of ammonia-monochloramine system in Helicobacter pylori--induced gastric
      mucosal injury].
AB  - Monochloramine is a reactive oxidant which is yielded by the reaction of
      neutrophil-derived hypochlorous acid and ammonia. Luminol-dependent
      chemiluminescence assay reveals that H. pylori directly elicits a respiratory
      burst of neutrophils. This activation is also observed by adding the bacterial
      supernatant of cultured or sonicated H. pylori, suggesting that H. pylori-derived
      soluble factor may be responsible for the release of chlorinated oxidants. In
      vitro cytotoxicity assay indicates that cultured rabbit gastric mucosal cells are
      significantly damaged by neutrophils which are stimulated by H. pylori. This
      injury is attenuated by urease inhibitor, antioxidants, and taurine
      (monochloramine scavenger). These data support the concept that ammonia
      monochloramine system plays an important role in H. pylori-associated gastric
      mucosal injury. Omeprazole and rebamipide significantly inhibit not only H.
      pylori-induced respiratory burst of neutrophils but also H. pylori-associated
      urease activity. This evidence emphasizes the advantageous effect of these anti
      ulcer compounds on H. pylori-positive gastric lesion and postulates a new
      strategy for anti-H. pylori treatment.

PMID- 8283625
TI  - [Leukotriene levels of Helicobacter pylori-infected gastric mucosa].
AB  - Helicobacter pylori appears to cause chronic active gastritis, which is
      characterized by infiltration by neutrophils. Leukotrienes (LTs), which are both
      chemotactic and cytotoxic, are produced mainly by neutrophils. We studied LT
      levels, H. pylori infection and neutrophils infiltration in gastric mucosa of
      patients with non-ulcer dyspepsia. LT levels of mucosa infected with H. pylori
      were higher than that in non-infected mucosa. There was a correlation between LT
      levels and neutrophils infiltration in H. pylori infected mucosa. H. pylori was
      sensitive to lipoxygenase inhibitor, AA-861, both in vitro and in vivo. Treatment
      with AA-861 decreased the severity of neutrophil infiltration. LTs may therefore
      be important in chronic active gastritis associated with H. pylori.

PMID- 8283627
TI  - [Isolation identification and quantitative culture of Helicobacter pylori from
      gastric mucosa].
AB  - The biopsy specimens were homogenized and diluted ten-fold serially in Hank's
      solution. Each dilution samples were streaked on Skirrow's selective medium. The
      plates were incubated at 37 degrees C 5 to 7 days under micro-aerobic condition
      and counting the viable cell of H. pylori. The positive rate of specimens with H.
      pylori in active gastric ulcer tissue (62.0%) was higher than that in scarred
      tissue (51.9%). Number of H. pylori viable cells in active ulcer tissue was
      significantly larger than in scarred tissue. The positive correlation between
      Raw's gastritis score of specimens from patients with erosive gastritis and
      number of H. pylori viable cells was clearly noticed.

PMID- 8283626
TI  - [Mucinase activity of Helicobacter pylori: application of simplified mucinase
      test].
AB  - We conducted the simplified mucinase tests about Helicobacters (Helicobacter
      pylori, Helicobacter felis and Helicobacter mustelae) and Campylobacter jejuni,
      positive controls were Pseudomonas maltophilia and Pseudomonas cepacia. H.
      pylori, H. felis and C. jejuni showed low resolution activities for hog gastric
      mucin, however H. mustelae had no detectable the activities. This enzymatic
      activity varies considerably by cultural condition of H. pylori, therefore it is
      difficult to compare the activity about each strain. This simplified mucinase
      test proved that H. pylori has some adverse effect on gastric mucin.

PMID- 8283628
TI  - [Detection of Helicobacter pylori by polymerase chain reaction].
AB  - The application of PCR method to the detection of H. pylori is reviewed. In most
      of the assays reported to date, primer pairs based on the sequences of urease and
      16S rRNA genes have been chosen. Clinical samples tested have ranged widely from
      gastric biopsy specimens to gastric aspirates, feces, dental plaques, saliva,
      etc. As few as one organism can be detected by the most sensitive assay. The
      reports suggest that PCR assay is suited for laboratory diagnosis of the organism
      as well as epidemiologic studies. A future problem is to search the target
      sequences which are more specific to H. pylori and more informative for
      researching pathogenesis of gastrointestinal disorders associated with H. pylori
      infection.

PMID- 8283629
TI  - [Endoscopic diagnosis of Helicobacter pylori distribution in human gastric mucosa
      by phenol red dye spraying method].
AB  - Helicobacter pylori (H. pylori) is known to show an uneven and patchy
      distribution on human gastric mucosa, close association with chronic gastritis
      and peptic ulcer diseases. The aim of this study was to clarify the distribution
      of this organism under direct vision by phenol red dye spraying endoscopy. In
      order to maintain gastric pH around pH 4.0 to 5.0, premedication was necessary
      either by intravenous injection of H2-blocker, 30 min before the test, or by oral
      administration of Omeprazole 20 mg or a half dose of H2-blocker before bedtime
      the day before the test. After that, 0.05% phenol red solution, containing 0.5 M
      urea, was sprayed onto the gastric mucosal via a teflon tube inserted through the
      endoscope. This technique was useful to clarify the distribution of H. pylori in
      the stomach in vivo and, it was possible to clinically study the role of H.
      pylori in upper G-I tract disorders, by this new technique.

PMID- 8283630
TI  - [Staining for Helicobacter pylori on gastric mucosa with dye from red cabbage
      during endoscopy].
AB  - Helicobacter pylori has a high urease activity and produces ammonia from urea,
      resulting in elevation of mucosal pH. Based on this characteristics of H. pylori,
      we have developed a method for staining H. pylori under endoscopy using dye from
      red cabbage (San-red RC, San-Ei Chemical Ind., Osaka), a pH indicator, safe for
      clinical use. After administration of a proton-pump inhibitor and an H2-receptor
      antagonist, the dye solution, mixed with 2% urea, was sprayed over the mucosa by
      endoscope. Change in color of the dye was found in some areas infected with H.
      pylori. The change in color reflects urease activity or amount of ammonia. This
      method may be useful to find the distribution of H. pylori in the mucosa and to
      examine the H. pylori-infected mucosa pathophysiologically.

PMID- 8283631
TI  - [Urease test].
AB  - In order to elucidate bacterial infection, as a rule, isolated and cultured
      bacteria of a specimen are identified by their morphologies or biochemical
      characteristics. However, the culture of Helicobacter pylori (H. pylori) is
      difficult and takes, much time. Therefore, favorable test results are currently
      obtained by combining the culture method, histopathologic method, urease test and
      sero-immunologic test. The merits of the urease test are that judgement is
      available immediately after endoscopy and that the test is inexpensive. The
      demerits are that the existence of H. pylori is diagnosed only by estimation that
      endoscopy is indispensable for the test. When compared with the culture method,
      the urease test has 91.8% sensitivity and 94.7% specificity and when compared
      with the histopathologic method, it has 94.4% sensitivity 88.4% specificity. In
      the future, the clinical requirement will increase for quick investigation on the
      evidence of H. pylori-induced infection. These results show that urease test is
      useful because it is simple and allows quick judgement.

PMID- 8283632
TI  - [13C-urea breath test].
AB  - The 13C-urea breath test is now a practical and readily available alternative to
      endoscopy- and serology-based methods for the detection of H. pylori infection.
      It can detect very low levels of H. pylori colonization within the stomach by
      assessing the entire mucosa, and avoids the risks of sampling error. We performed
      the 13C-urea breath test in asymptomatic volunteers and patients with gastric and
      duodenal ulcers in order to compare the sensitivity and specificity by
      measurement of H. pylori antibody by ELISA. The positive rates of H. pylori in
      the 13C-urea breath test was correspondent with the results from the H. pylori
      antibody test, although no correlation in the antibody titers and urease
      activities was observed between the two methods. The 13C-urea breath test was the
      most useful method in evaluation of eradication of H. pylori after administration
      of antibiotics, compared to serological and pathological methods. These results
      suggest that the 13C-urea breath test is highly useful for the diagnosis of H.
      pylori infection of the gastric mucosa.

PMID- 8283633
TI  - [ELISA tests for detection of Helicobacter pylori antibodies].
AB  - The efficacy of commercial ELISA tests for detection of Helicobacter pylori
      antibodies was investigated. Some investigators reported that six commercial
      ELISA tests had sensitivities of 81-96%, and had specificities of 29-96%. It is
      possible that some of false-negative results by ELISA may occur for patients who
      are in the acute phase of infection. When ELISA tests gave false-positive
      results, it should be taken into account that there might be some false negative
      diagnoses for the gastric H. pylori status, arising from sampling errors. Some of
      the false-positive results by ELISA might indicate the previous infection only.

PMID- 8283634
TI  - [Prevalence and distribution of Helicobacter pylori in the stomach of patients by
      upper gastrointestinal endoscopy].
AB  - The prevalence of H. pylori colonization in the antrum and body was examined in
      patients with gastritis, duodenal ulcer (DU) and gastric ulcer (GU). The total
      prevalence was 63.5%, 90.0% and 85.5%, respectively. In patients with gastritis
      and DU, the frequency was similar at both sites, while in GU patients H. pylori
      positivity was increased markedly in the body compared with the antrum.
      Furthermore, in patients with antral and angular ulcers, biopsy studies from 8
      different sites showed that the H. pylori density score was significantly higher
      at the ulcer sites than at the non-ulcer sites. H. pylori infection is strongly
      implicated in the pathogenesis of gastritis and peptic ulceration.

PMID- 8283635
TI  - [Helicobacter pylori and gastroduodenal ulcers].
AB  - We studied the prevalence of Helicobacter pylori (H.P.) infection in
      gastroduodenal diseases. H.P. was positive in 67.6% of gastric ulcer patients and
      82.2% of duodenal ulcer patients. H.P. was detected with high frequency
      throughout the course of ulcer healing. Short-term antimicrobial therapy,
      including cefixim, ofloxacin and bismuth subnitrate, was effective in 50% of H.P.
      positive patients. However, H.P. was detected again in a considerable number of
      patients one year after the treatment. Histological inflammation of the antral
      mucosa of the stomach was stronger in H.P. positive patients than that in H.P.
      negative patients. Eradication of H.P. had an improving effect on the
      inflammation of the stomach, irrespective of the use of concomitant drugs.

PMID- 8283636
TI  - [Role of Helicobacter pylori infection in gastric metaplasia in the duodenum in
      the production of duodenal ulcer].
AB  - Helicobacter pylori (H. pylori) is frequently detected in not only the antrum but
      also the gastric juice and the duodenum with gastric metaplasia, which is
      believed to be a response of duodenal mucosa to injury by hyperacidity, in most
      of duodenal ulcer patients. Conversely, the normal duodenum is not infected with
      H. pylori in non-duodenal ulcer patients, even if H. pylori is present in the
      antrum and/or the gastric juice. All patients with H. pylori in the duodenum has
      the H. pylori infection in the gastric antrum. Patients with H. pylori in the
      gastric juice also has H. pylori infection in the antrum. These findings may
      support the following hypothesis in the formation of duodenal ulcer. A high
      duodenal acid load leads to the formation of gastric metaplasia in the duodenal
      bulb, where can be easily infected by gastric H. pylori through the gastric
      juice. As a result of the duodenal colonization of H. pylori, the duodenal mucosa
      impaired by ammonia of H. pylori could has the formation of duodenal ulcer.

PMID- 8283637
TI  - [The role for Helicobacter pylori infection in intractable and recurrent ulcer].
AB  - Patients with intractable peptic ulcer or recurrent peptic ulcer have high rate
      of Helicobacter pylori infection. To study the effect of H. pylori on the
      recurrence of peptic ulcer, we treated the patients, who had H. pylori infection,
      with antibiotics (amoxicillin, clarithromycin, fosfomycin). After one year, none
      of peptic ulcer patient in whom H. pylori was eradicated had a recurrence. Among
      patients who remained positive for H. pylori, the ulcer relapse rate was 61% (11
      of 18). In patients who were successfully eradicated of H. pylori with
      antibiotics the rate of recurrence was reduced. Patients with both intractable
      peptic ulcer and H. pylori infection were treated with antibiotics. Eradication
      of H. pylori induced ulcer healing. These findings suggest an important role for
      H. pylori in intractable and recurrent peptic ulcer.

PMID- 8283638
TI  - [Relationship between Helicobacter pylori colonization in the gastric mucosa and
      the severity of atrophic gastritis].
AB  - We studied the relationship between Helicobacter pylori infection and atrophic
      gastritis. Eighty non-ulcer patients underwent endoscopy with biopsy. Detection
      and quantitative assessment of H. pylori was made based on smear, culture and
      tissue section (Gram stain). The extent of atrophic gastritis was assessed
      endoscopically according to the classification of Kimura and Takemoto. Severity
      of glandular atrophy and intestinal metaplasia was assessed histologically. H.
      pylori infection was accompanied by or preceded the extension of atrophic
      gastritis. In patients with severe atrophic gastritis H. pylori was not detected.
      In the advanced stage of atrophic gastritis H. pylori might be cleared from the
      gastric mucosa. Our results suggest that H. pylori may be one of the factors for
      the extension of atrophic gastritis.

PMID- 8283639
TI  - [Helicobacter pylori and the development of atrophic gastritis].
AB  - A close relationship between H. pylori infection and atrophic gastritis has been
      reported, and atrophic gastritis has been thought of as one of the precursors of
      gastric carcinoma. It was reported that there was a significant positive
      correlation between the reduction of serum pepsinogen (PG) I/II ratio and the
      progression of atrophic gastritis. The ratio of PG I/II was significantly
      decreased in H. pylori positive patients when compared to H. pylori negative
      patients with chronic gastritis. The PG I/II ratio in gastric cancer was
      significantly lower than that of chronic gastritis, while the prevalence of H.
      pylori was not significant difference between gastric carcinoma and chronic
      gastritis. It is suggested that there is strong correlation between H. pylori
      infection and the development of atrophic gastritis, and that eradication of H.
      pylori from gastric mucosa might reduce the risk of developing gastric carcinoma.

PMID- 8283640
TI  - [Helicobacter pylori infection in gastric cancer].
AB  - The relationship between Helicobacter pylori (H. pylori) infection and gastric
      cancer becomes the topics in the world, since some reports thereon in 1991. The
      purpose of this study was to know the prevalence of H. pylori infection in many
      patients with gastric cancer. We examined the H. pylori IgG antibody in 507
      patients with gastric cancer resected surgically in our hospital from 1989 to
      1991, retrospectively. For the test of H. pylori IgG antibody, HM-CAP EIA kit
      (Italy, ENTERIC PRODUCTS Co.) was used. The overall detection rate of H. pylori
      IgG antibody was 75% (378/507). H. pylori infection was significant significantly
      frequent in early cancer (80%, 231/288) than advanced cancer (67%, 147/219). But,
      the other clinicopathological features such as sex, age, histological type,
      location and the degree of intestinal metaplasia were not significantly
      correlated with H. pylori infection. To evaluate the risk of H. pylori infection
      for gastric cancer, we are going to plan a matched-pair case-control study.

PMID- 8283641
TI  - [Helicobacter pylori and gastric cancer in view of relation to atrophy of
      background gastric mucosa].
AB  - To make clinical assessment regarding the role of Helicobacter pylori (H. pylori)
      in the occurrence of gastric cancer, we examined serological and microbiological
      positive rate of H. pylori and histological and endoscopic findings of atrophic
      gastritis of background mucosa in 149 gastric cancer patients, 136 gastric ulcer
      patients, 82 chronic gastritis cases and 46 normal control. Serological H. pylori
      positive rate examined using GAP-IgG in 43 gastric cancer patients was 95%, which
      was significantly higher than normal control (4%) but the same level as in
      chronic gastritis cases (87%) and gastric ulcer patients (93%). While,
      Microbiological H. pylori positive rate by culture was 62% in 149 gastric cancer,
      7% in normal control, 74% in chronic gastritis and 80% in gastric ulcer. H.
      pylori infection and the degree of lymphocyte infiltration were significantly
      correlated and H. pylori was frequently detected in the cases with mild and
      moderate atrophic gastritis in all groups. No difference was observed in H.
      pylori positive rate between the well and poorly differentiated cancer cases; 96%
      and 94% by GAP-IgG, 57% and 66% by culture, respectively. As a conclusion, it was
      suspected that the relation between H. pylori infection and gastric cancer was
      indirect and associated with atrophic process of background mucosa.

PMID- 8283642
TI  - [Clinico-pathological study of Helicobacter pylori in early gastric cancer].
AB  - The role of Helicobacter pylori (Hp) infection in the pathogenesis of various
      gastric diseases is an important but unresolved issue. To investigate the
      association between Hp and the histological findings of the stomach in patients
      of early gastric cancer, the prevalence of Hp in gastric mucosa and the mucosal
      alterations were examined histo-pathologically in the surgically resected stomach
      of 30 cases with early gastric cancer. Serum IgG antibodies for Hp were
      determined in these cases. All 30 cases had evidence of Hp infection in resected
      stomach and 90% had Hp antibodies in their serum. There was no evidence of direct
      association between Hp and gastric cancer histopathologically, although it is
      considered that chronic gastritis (atrophy and intestinal metaplasia) are
      implicated in Hp infection.

PMID- 8283643
TI  - [In vitro anti-microbial activity against H. pylori and clinical efficacy of
      various drugs].
AB  - The in vitro antimicrobial activity against H. pylori and clinical efficacy of
      various antibiotics and antiulcer drugs are summarized in this study. H. pylori
      highly sensitive to most of the beta-lactams and macrolides. Especially,
      amoxicillin and clarithromycin have satisfactory in vitro activity against H.
      pylori. The anti-ulcer drugs, sofalcon and plaunotol, used in Japan as mucosal
      protective agents, also have a weak activity against H. pylori with MIC50 12.5
      micrograms/ml and MIC90, 50-100 micrograms/ml, while H2-receptor antagonists do
      not have in vitro activity. Efficacy of antibiotics as monotherapy for
      eradicating H. pylori is rather poor. The best results with monotherapy are
      obtained with clarithromycin and amoxicillin. Omeprazole monotherapy suppresses
      H. pylori infection but does not eradicate H. pylori. Combined therapy with
      omeprazole and amoxicillin have strong synergistic effects on the eradication of
      H. pylori (68.8%). Newly developed proton pump inhibitors, such as lansoprazole,
      E-3810 and their derivatives, showed strong in vitro activity against H. pylori
      suggesting that these drugs may be useful for the treatment of H. pylori
      infection.

PMID- 8283645
TI  - [Effective regimen for eradication of Helicobacter pylori].
AB  - There is now substantial evidence that Helicobacter pylori (H. pylori) is both a
      frequent cause of chronic gastritis and an important factor in the recurrence of
      duodenal ulcer. However, to achieve the eradication of H. pylori is very
      difficult and although a number of treatment regimens suppress this organism, the
      stomach usually becomes recolonized shortly after the cessation of treatment.
      Many reports have shown that polytherapy is more effective than monotherapy. And
      so, the best results have been achieved with triple therapy using combination of
      bismuth, metronidazole, or tinidazole, and amoxicillin or tetracycline. The
      factor influencing effectiveness of triple therapy is compliance with the
      prescribed medications. And so, short term triple therapy is highly effective and
      well tolerated.

PMID- 8283644
TI  - [Activity of Lansoprazole (new proton pump inhibitor) against Helicobacter pylori
      and its therapeutic efficacy].
AB  - Lansoprazole, one of PPIs, is a strong antacid and it cures stomach and duodenal
      ulcers at early stages as well as having antibiotic action towards HP. The in
      vitro MIC of the product is between 3.13 and 12.5 micrograms/ml and it was 12.5
      micrograms/ml, which was the same as MIC of colloidal bismuth citrate, in our
      study. Sterilizing effect of Lansoprazole is reported to be the direct attack on
      HP bacteria from electron microscopic findings. Our study revealed that
      Lansoprazole would preserve the epithelial cells on the edge of a stomach ulcer
      and would protect PAS-positive substance within them. Lansoprazole is said to
      cure many H2-Blocker resistant ulcers and to suppress the rate of recurrence of
      stomach and duodenal ulcers. These effects are considered to be attributable to
      maintenance of mucous barrier and maintenance of cytoprotection of the gastric
      mucosa by Lansoprazole as well as its sterilizing action mainly on HP.

PMID- 8283646
TI  - [Eradication therapy of Helicobacter pylori in gastroduodenal ulcer and its long
      term course].
AB  - We investigated the efficacy of antimicrobial drugs, amoxicillin and
      clarithromycin that have the in vitro activity against H. pylori, and observed a
      long term course of ulcer after eradication. The eradication rate of combination
      therapy with PPI and amoxicillin showed best result (13/18: 72%). In eradicated
      cases, index of PAS positive substance and gastritis score in antral mucosa that
      is histological examination was improved, and ammonia concentration in gastric
      secretions decreased. The recurrent rate of ulcer in long term course after
      eradication was investigated, the recurrent rate of ulcer was significantly lower
      in H pylori eradicated cases than in H. pylori continuously positive cases.
      Results suggest that eradication of H. pylori may be controlled recurrence of H.
      pylori positive peptic ulcer.

PMID- 8283647
TI  - [The effect of the eradication of H. pylori on the intractable ulcer].
AB  - On 25 cases (gastric ulcer 14 cases and duodenal ulcer 11 cases) of the
      intractable ulcer which was H. pylori-positive, we eradicated H. pylori. The
      eradication was done during 14 days by a triple therapy: bismuth subnitrate 2.0
      g, metronidazole 0.75 g, AMPC 0.75 g/day). All cases were confirmed to be
      eradicated by culture and microscopic examination. 24 cases (gastric ulcer 13/14
      and duodenal ulcer 11/11) were confirmed to be completely cured. After the
      eradication, we ceased the maintenance therapy by H2RA and followed them up,
      however, no ulcer relapses were found up to 9 months. It was considered that the
      eradication against H. pylori was a very effective method to the intractable
      ulcer.

PMID- 8283648
TI  - [DNA topoisomerase inhibitor].
AB  - DNA topoisomerases are enzymes involved in various aspects of genetic processes
      by catalyzing a topological change of DNA. Topoisomerase is now viewed as an
      important cellular target of antitumor drugs. These drugs targeting topoisomerase
      have been used to establish a relationship between drug-induced cleavable complex
      formation and cytotoxicity. Topoisomerase I is shown to be the cellular target of
      camptothecin and its derivatives. And topoisomerase II targeting drugs are both
      intercalative drugs (acridines, ellipticines, anthracyclines) and non
      intercalative drugs (epipodophyllotoxin derivatives). And then Irinotecan,
      topotecan, sobuzoxane and IST-622 are unique topoisomerase inhibitors and are
      under investigation in Japan, the new antitumor drugs targeting topoisomerases
      are reviewed.

PMID- 8283649
TI  - [Human Y chromosome in reproduction and development].
AB  - The present status of human Y chromosome study is reviewed. A total of 13 genes,
      including two pseudogenes, have been mapped on the Y chromosome. They included
      colony stimulating factor receptor (CSF2R), SRY (TDF), ZFY, RPS4Y (ribosome
      protein 4S), ADMLY (Kallman syndrome), AMGL (amelogenin, which we cloned
      ourselves) and so on. In addition, the presence of two XY homologous genes is
      proposed. One increases performance IQ and the other reduces water-content of an
      embryo. We examined 54 azoospermic patients with an apparently normal Y
      chromosome. Each patient was analyzed for the presence or absence of 26 loci on
      the Y chromosome. Six showed a very small "micro" deletion. A common segment
      which is absent in every 6 patient has been identified. Cloning of azoospermia
      related gene is being attempted using YAC clones.

PMID- 8283650
TI  - [Betacellulin: a new growth factor for vascular smooth muscle cells].
AB  - Betacellulin, a new member of the epidermal growth factor family, has been
      purified from the conditioned media of mouse pancreatic beta tumor cells.
      Purified betacellulin is a single chain glycoprotein with a molecular weight of
      approximately 32K. This factor is a potent mitogen for retinal pigment epithelial
      cells and vascular smooth muscle cells. Molecular cloning of the mouse and human
      cDNAs reveals that the mature form of this factor, composed of 80 amino acid
      residues, appears to be processed from a larger transmembrane precursor by
      proteolytic cleavage. Seventy nine % amino acid similarity is present between
      mouse and human precursor proteins. The carboxyl-terminal domains of both mouse
      and human betacellulins have a 50% sequence similarity with that of rat
      transforming growth factor alpha. The betacellulin gene is found to be expressed
      in several mouse tissues, including kidney, liver and pancreatic beta cells.

PMID- 8283651
TI  - [Clinical experience of Rotablator].
AB  - 26 patients (27 lesions) who had severe calcified and diffuse lesions underwent
      Rotablator treatment, lesion characteristics were type B2, Type C of AHA/ACC
      classification. There were no patients who had type A1, type B1 lesions.
      Procedural success rate is 96%, coronary perforation occurred in one patient but
      not necessary for surgical treatment. Non Q myocardial infarction occurred only
      in one patient. Follow up Angioplasty were performed 1 and 3 months later after
      procedures. There were no restenosis after 1 month, but after 3 months, 56% of
      patients had restenosis.

PMID- 8283652
TI  - [Cerebral stroke in the era of CT & MRI--introduction].

PMID- 8283653
TI  - [Analysis of cerebral hemodynamics with FID-CT].

PMID- 8283654
TI  - [Development of the DSA and technique for the cerebrovascular disease: IVDSA and
      IADSA].

PMID- 8283655
TI  - [Advances in instrumentation of MRI and diagnostic imaging of the brain].

PMID- 8283656
TI  - [MR angiography in the diagnosis of intracranial vascular lesions].

PMID- 8283657
TI  - [Magnetic resonance spectroscopy (MRS) and chemical shift imaging (CSI) studies
      on cerebral metabolism in cerebrovascular disease].

PMID- 8283658
TI  - [Update on neurosonology].

PMID- 8283659
TI  - [Duplex carotid ultrasonography].

PMID- 8283660
TI  - [Cerebral blood flow measurement using single photon emission computed
      tomography].

PMID- 8283661
TI  - [Measurement of regional cerebral metabolism using PET].

PMID- 8283662
TI  - [Magnetoencephalography].

PMID- 8283663
TI  - [Antithrombotic drug (thrombolytic drug, anticoagulant, antiplatelet drug)].

PMID- 8283664
TI  - [Agents for treatment of brain edema].

PMID- 8283665
TI  - [Medical treatment for cerebral vasospasm].

PMID- 8283666
TI  - [Epidemiology of stroke in Japan, its trend and up-to-date knowledge].

PMID- 8283667
TI  - [Cerebral circulatory and metabolic improver].

PMID- 8283668
TI  - [A trend of surgical treatment for cerebrovascular disease].

PMID- 8283669
TI  - [Management of acute cerebrovascular disease--diagnostic methods and guideline of
      initial treatment].

PMID- 8283670
TI  - [Clinical grading in acute stage of cerebrovascular disease].

PMID- 8283671
TI  - [Cerebral edema and herniation].

PMID- 8283672
TI  - [Organization, system and management in stroke intensive care unit or
      neurological intensive care unit].

PMID- 8283673
TI  - [New network for emergency medical services of stroke with CT-picture
      teleradiology system].

PMID- 8283674
TI  - [Recent advances in stroke rehabilitation].

PMID- 8283675
TI  - [A new evaluation instrument for stroke patients].

PMID- 8283676
TI  - [Practice of stroke rehabilitation].

PMID- 8283677
TI  - [Treatment and management of chronic cerebrovascular disease].

PMID- 8283678
TI  - [Hypertension].

PMID- 8283679
TI  - [Anatomy of the cerebrovascular system].

PMID- 8283680
TI  - [Hyperlipidemia, arteriosclerosis].

PMID- 8283682
TI  - [Heart diseases].

PMID- 8283681
TI  - [Diabetes mellitus].

PMID- 8283683
TI  - [Stroke and multiphasic screening for cerebral disorders].

PMID- 8283684
TI  - [Classification of ischemic stroke and frequency distribution].

PMID- 8283685
TI  - [Genesis and risk factors for ischemic stroke].

PMID- 8283686
TI  - [Pathological epidemiological study in the etiology of cerebral infarction].

PMID- 8283687
TI  - [Pathological study of vascular response to embolism].

PMID- 8283688
TI  - [CT diagnosis of cerebral infarction].

PMID- 8283689
TI  - [MRI diagnosis of cerebral infarction].

PMID- 8283690
TI  - [Cerebral angiography for the patient with occlusive cerebrovascular disease-
      check points for analysis].

PMID- 8283691
TI  - [Implication of carotid atherosclerosis and ischemic cerebrovascular disease, an
      ultrasonic study].

PMID- 8283692
TI  - [Carotid bruit and stroke].

PMID- 8283693
TI  - [Ischemic stroke with a special reference to alteration in blood pressure and
      cerebral circulation].

PMID- 8283694
TI  - [Biochemistry of brain ischemia--mechanism of delayed neuronal death].

PMID- 8283695
TI  - [Temporal profiles of regional cerebral blood flow and metabolism after cerebral
      ischemia].

PMID- 8283696
TI  - [Issues of therapy for cerebral infarction--from the view-point of CBF].

PMID- 8283697
TI  - [Hemocoagulation disorders in cerebral ischemia].

PMID- 8283698
TI  - [The diagnostic criteria of cerebral infarction and the differential diagnosis
      between cerebral infarction and cerebral hemorrhage].

PMID- 8283699
TI  - [Predicting functional outcome following acute cerebral infarction].

PMID- 8283700
TI  - [The treatment of acute cerebral infarction with urokinase and tissue plasminogen
      activator].

PMID- 8283701
TI  - [Anticoagulant therapy in stroke].

PMID- 8283702
TI  - [Fluid dynamics and rheology of cerebral blood circulation].

PMID- 8283703
TI  - [Indication and efficacy of hemodilution therapy on patients with acute ischemic
      stroke].

PMID- 8283704
TI  - [Prevention of vascular disease and antiplatelet treatment].

PMID- 8283705
TI  - [Use of drugs acting on cerebral circulation and metabolism].

PMID- 8283706
TI  - [Indication of EC/IC bypass for an occlusive cerebrovascular disease].

PMID- 8283707
TI  - [Indication of carotid endarterectomy].

PMID- 8283708
TI  - [Secondary prevention of brain infarction].

PMID- 8283709
TI  - [Rehabilitation of cerebral infarction--its methods and evaluation of
      dysfunction].

PMID- 8283710
TI  - [Pathophysiology of atheromatous cerebral infarction--hemodynamic ischemia and
      artery-to-artery embolism].

PMID- 8283711
TI  - [Physiology of cerebral blood flow and metabolism].

PMID- 8283712
TI  - [Neuroradiological diagnosis of thrombotic non-lacunar cerebral infarction].

PMID- 8283713
TI  - [Artery-to-artery embolism--clinical assessment and evaluation].

PMID- 8283714
TI  - [Treatment of atherothrombotic brain infarction--pharmacological treatment and
      indication of surgical operation].

PMID- 8283715
TI  - [Prognosis of atherosclerotic cerebral infarction].

PMID- 8283717
TI  - [Clinical statistics on cardiogenic brain embolism].

PMID- 8283716
TI  - [The long term follow-up of carotid endarterectomy].

PMID- 8283718
TI  - [Clinical features and diagnosis of cardioembolic stroke].

PMID- 8283719
TI  - [Spectacular shrinking deficit in cardiogenic cerebral embolism].

PMID- 8283720
TI  - [Characteristic CT findings in cerebral embolism].

PMID- 8283721
TI  - [MR diagnosis of hyperacute stage of embolic cerebral infarction].

PMID- 8283722
TI  - [Utility and accuracy of the diagnostic techniques for detecting intracardiac
      thrombi in embolic stroke].

PMID- 8283723
TI  - [Nonvalvular atrial fibrillation (NVAF) as an important cause of cerebral
      embolism].

PMID- 8283724
TI  - [Recent progress in neurochemistry and neuronal death of ischemic brain].

PMID- 8283725
TI  - [Thrombolytic and anticoagulation therapy for acute cardioembolic stroke].

PMID- 8283726
TI  - [Stroke prevention and prognosis in cardiogenic brain embolism].

PMID- 8283727
TI  - [Primary prevention for brain embolism in cardiac disorders].

PMID- 8283728
TI  - [Lacunar infarcts and infarcts in the territory of deep perforators--concepts and
      definitions].

PMID- 8283729
TI  - [Morphological features of 'lacunes'].

PMID- 8283730
TI  - [Mechanism in lacunar infarction].

PMID- 8283731
TI  - [Classification of lacunar stroke--subtypes and lesions].

PMID- 8283732
TI  - [Imaging of infarcts in the distribution of the basal perforating arteries;
      correlation with anatomical study].

PMID- 8283733
TI  - [Therapy and prognosis of lacunar infarction].

PMID- 8283734
TI  - [The molecular mechanism of atherogenesis and thrombogenesis].

PMID- 8283735
TI  - [Border zone infarction: definition, classification and pathogenesis].

PMID- 8283736
TI  - [Hemorheology in border zone infarction].

PMID- 8283737
TI  - [Changes in the classification of cerebrovascular diseases in Japan and other
      countries].

PMID- 8283738
TI  - [The clinical status of superficial watershed infarction--pathophysiology,
      clinical findings and diagnostic imaging].

PMID- 8283739
TI  - [Pathophysiology, clinical symptoms and neuroimaging of deep border zone
      infarction].

PMID- 8283740
TI  - [Vascular supply and infarction of the brain stem].

PMID- 8283741
TI  - [Brainstem infarct--frequency, background factors and pathogenesis].

PMID- 8283742
TI  - [Specific neurological syndromes in brainstem infarction--localization of the
      cranial nerve nuclei and its importance in the diagnosis].

PMID- 8283743
TI  - [MRI in brainstem infarction].

PMID- 8283744
TI  - [Treatment and prognosis of brainstem infarction].

PMID- 8283745
TI  - [Clinical aspects of midbrain infarction].

PMID- 8283746
TI  - [Pontine infarction].

PMID- 8283747
TI  - [Pathogenetic and morphological features of brain infarction].

PMID- 8283748
TI  - [Medullary infarction].

PMID- 8283749
TI  - [Neuropathological and clinical aspects of cerebellar infarction].

PMID- 8283750
TI  - [Clinical aspects of striatocapsular infarction].

PMID- 8283751
TI  - [Cerebral infarction of Binswanger type: its general concept, pathology, etiology
      and clinical feature].

PMID- 8283752
TI  - [Cerebral circulation and neuroimaging in Binswanger-type infarction].

PMID- 8283753
TI  - [Cerebral hemorrhagic infarction; clinical importance and epidemiological studies
      of consecutive autopsy series].

PMID- 8283754
TI  - [Pathology and the mechanism of hemorrhagic cerebral infarction].

PMID- 8283756
TI  - [Prevention and treatment of hemorrhagic infarction].

PMID- 8283755
TI  - [CT and MRI diagnosis of hemorrhagic infarction].

PMID- 8283757
TI  - [Concept and clinical features of Gaisbock syndrome--as importance for a high
      risk group of cerebral infarction].

PMID- 8283758
TI  - [Treatment and stroke prevention in patients with Gaisbock syndrome].

PMID- 8283759
TI  - [Arterial lesion and mechanism of arterial rupture in hypertensive intracerebral
      hemorrhage].

PMID- 8283760
TI  - [Asymptomatic cerebral infarction and advance in magnetic resonance imaging].

PMID- 8283761
TI  - [Magnetic resonance imaging study of asymptomatic ischemic lesions].

PMID- 8283762
TI  - [Risk factors of silent infarction].

PMID- 8283763
TI  - [Asymptomatic lacunar stroke on magnetic resonance imaging in the normal
      elderly].

PMID- 8283764
TI  - [Silent multi-lacunar lesions on magnetic resonance imaging in asymptomatic
      hypertension].

PMID- 8283765
TI  - [Incidental strokes in diabetic patients detected by MRI].

PMID- 8283766
TI  - [Hyperlipidemia].

PMID- 8283767
TI  - [Nuclear magnetic resonance image and CT scan studies on silent strokes in non
      valvular atrial fibrillation (NVAF)].

PMID- 8283768
TI  - [Asymptomatic carotid lesion and silent cerebral infarction].

PMID- 8283769
TI  - [Asymptomatic cerebral infarction of the vertebrobasilar system].

PMID- 8283770
TI  - [Cerebral blood flow in asymptomatic individuals--relationship with
      cerebrovascular risk factors and MRI].

PMID- 8283771
TI  - [Cerebral white-matter lesions and leuko-araiosis in asymptomatic cerebral
      infarctions].

PMID- 8283772
TI  - [The progress of diagnosis of cerebrovascular disease by cranial computed
      tomography].

PMID- 8283773
TI  - [The relationship between silent stroke and cognitive function].

PMID- 8283774
TI  - [Prevention for stroke in patients with silent cerebral infarction].

PMID- 8283775
TI  - [A classification and outline of transient cerebral ischemic attack].

PMID- 8283776
TI  - [High magnetic field intensity MRI findings of transient ischemic attack].

PMID- 8283777
TI  - [Pathogenesis of transient ischemic attacks: imaging approach with MRI,
      angiography and SPECT].

PMID- 8283778
TI  - [Positron emission tomography in transient ischemic attacks].

PMID- 8283779
TI  - [Pathogenesis of amaurosis fugax].

PMID- 8283780
TI  - [Pathogenesis and clinical aspects of carotid TIA].

PMID- 8283781
TI  - [Pathogenesis and clinical aspects of vertebrobasilar TIA].

PMID- 8283782
TI  - [Prognosis in patients with transient ischemic attacks: progress rate to complete
      strokes].

PMID- 8283783
TI  - [Completed stroke-preventive strategies and medical treatment in patients with
      TIA].

PMID- 8283784
TI  - [Computed angiotomography for diagnosis of cerebrovascular diseases].

PMID- 8283785
TI  - [Reversible ischemic neurological deficit (RIND)].

PMID- 8283786
TI  - A follow-up study of resected stomach cancer patients with special emphasis on
      the incidence of second primary cancers.
AB  - The causes of death in long-term survivors of stomach cancer after a gastrectomy
      have been investigated in a follow-up study of 320 such patients, with special
      focus on the postoperative development of a second primary cancer. The five- and
      10-year overall survival rates of early stomach cancer patients were 87.5 and
      75.8%, respectively, and of advanced stomach cancer patients, 44.2 and 37.5%,
      respectively. A multivariate analysis identified the patient's age and stage of
      cancer at the time of diagnosis as separate prognostic factors for overall
      survival. During the observation period, 15 (4.7%) patients developed a second
      primary cancer, so that no significantly elevated risk of developing a second
      primary cancer was demonstrated. During the same observation period, however, 48
      (15%) of the patients died of a non-cancerous disease, 12 succumbing to an acute
      myocardial infarction and/or heart failure. Given these results, it is felt that
      continued follow-up of long-term stomach cancer survivors should be pursued to
      prevent or impede the development of a non-cancerous disease and/or a second
      primary cancer, so that the life of such former patients can be prolonged.

PMID- 8283787
TI  - Clinical and pathological analyses of patients with a family history of
      colorectal cancer. Registry Committee, Japanese Research Society for Cancer of
      the Colon and Rectum.
AB  - Patients who were registered by the Japanese Society for Cancer of the Colon and
      Rectum between 1978 and 1983 were examined clinically and pathologically, in
      terms of colorectal cancer with familial accumulation. The incidence of patients
      with a family history of colorectal cancer (FH+ group)--patients with
      adenomatosis coli were excluded--was 6.5% in 15,369 colorectal cancer patients.
      The incidence of patients with a family history of malignant tumors other than
      colorectal cancer was 27.7%. Comparison of the FH+ group with the FH- group
      (patients without a family history of colorectal cancer) revealed the incidence
      of colonic cancer to be significantly higher than that of rectal cancer in the
      FH+ group (P < 0.01). The patients with colonic cancer in the FH+ group were
      significantly younger than those in the FH- group (P < 0.01), but there was no
      age-dependent difference between patients with rectal cancer in the two groups.
      There was no difference in sex ratio and there was little difference in the
      subsite of the primary lesion in the colon between the FH+ and FH- groups. The
      incidence of multiple primary colorectal cancer was significantly higher in
      patients with colonic cancer in the FH+ group than in the FH- group (P < 0.01).
      The incidence of multiple primary cancer in sites other than the colon and rectum
      was significantly higher in the FH+ group (P < 0.01), but no significant
      difference was found in the site of lesions. The prognosis of patients in the FH+
      group was significantly better than that of those in the FH- group; however,
      there were no differences in background factors such as findings of the primary
      lesion, status of metastasis, clinical stage and rate of curative resection
      between the groups.

PMID- 8283788
TI  - Mutational heterogeneity among individual tumors in a case of multiple primary
      malignancy of the colon.
AB  - c-Ki-ras mutations were analyzed from quintuple colon tumors in a 75-year-old
      patient with no family history of colon cancer. Polymerase chain reaction
      amplified DNA was sequenced for mutations in c-Ki-ras exon 1. Detected mutations
      were confirmed with allele-specific PCR which amplified only mutant sequences.
      Five tumors were histopathologically diagnosed as: adenoma with moderate atypia,
      adenoma with moderate atypia bearing a focal cancer, adenoma with severe atypia
      bearing a focal cancer, intramucosal carcinoma, well differentiated
      adenocarcinoma (advanced). Transitions, G-A, were found at the second base of
      codon 12 for the adenoma with severe atypia bearing a focal cancer and for the
      well- differentiated adenocarcinoma. The same substitution was found at the
      second base of codon 13 in the adenoma with mild atypia bearing a focal cancer.
      No base substitution at codon 12 or 13 was found for the intramucosal carcinoma
      nor for the adenoma with moderate atypia. These findings demonstrated there to be
      heterogeneous genetic and histopathological alterations in the individual tumors
      of the present case of synchronous malignancy of the colon.

PMID- 8283789
TI  - Feasibility and pharmacokinetics of continuous subcutaneous infusion of low-dose
      interferon-gamma: a pilot study.
AB  - Continuous subcutaneous infusion of interferon-gamma was carried out in an
      attempt to improve the therapeutic efficacy of the agent, one of the most potent
      immunomodulatory cytokines. Seven patients with renal cell carcinoma underwent
      the therapy using battery-powered micro-infusion pumps. In four patients,
      recombinant human interferon-gamma, 15 x 10(6) JRU (Japan Reference Unit)/body,
      was administered subcutaneously and continuously for five days. The therapy was
      repeated without interruption up to three times in four patients, including one
      for whom a single course of five-day therapy had been given three months
      previously. The major side effects were fever, anorexia, general malaise and
      local skin reaction. Discontinuation of the therapy was necessary in two
      patients, one in single five-day therapy and the other in repeated therapy, due
      to generalized skin eruption and general malaise, respectively. Serum interferon
      gamma levels, as determined by radioimmunoassay, increased gradually and reached
      20-30 IU/ml on day 4 or 5. Among patients who received two or three courses of
      therapy, the interferon-gamma levels showed high inter-individual differences
      after day 6. The levels gradually fell after the therapy terminated with a half
      life of about 2 days. No clinical response was observed. Our data suggest that
      interferon-gamma can be administered by continuous subcutaneous infusion, and
      warrants further study.

PMID- 8283790
TI  - Phase II trial of UFT activity in pretreated breast cancer patients.
AB  - Seventy metastatic breast adenocarcinoma patients, pretreated with standard
      hormonotherapy or chemotherapy, received continuous UFT at 10 mg/kg/day, orally,
      for at least two months. There were one complete response (1.5%), 12 partial
      responses (17%), one minor response and 37 disease stabilizations. The median
      duration of response was nine months. A greater efficacy was demonstrated in 29
      patients with soft tissue disease, with a rate of 38% objective responses. The
      major toxicity was gastrointestinal, with 45% of patients developing nausea and
      vomiting and 30%, diarrhea. Bone marrow toxicity was slight. UFT has shown
      antitumor activity in our group of pretreated patients, especially these with the
      cutaneous tumoral and/or inflammatory form of the disease.

PMID- 8283791
TI  - Small cell carcinoma of the esophagus with an esophago-mediastinal fistula
      successfully treated by chemoradiation therapy and intubation: a case report.
AB  - A case of esophageal small cell carcinoma with cervical node metastases and an
      esophago-mediastinal fistula was treated successfully by chemoradiotherapy. The
      fistula, after irradiation, was handled successfully by esophageal intubation,
      followed by infusional 5-fluorouracil and cisplatinum chemotherapy, resulting in
      the closure of the fistula. Two courses of concurrent chemoradiotherapy, followed
      by additional cisplatinum and etoposide chemotherapy, were administered. The
      tumor, including the cervical lymph node metastases, disappeared completely after
      the treatment.

PMID- 8283792
TI  - Regression of pulmonary and multiple skeletal metastases from renal cell
      carcinoma by nephrectomy and alpha-interferon therapy: a case report.
AB  - We report a rare case of advanced renal cell carcinoma in a patient who showed
      complete resolution of metastases to the lung and bones after nephrectomy,
      partial jejunectomy and subsequent alpha-interferon therapy. The patient was a 54
      year-old man whose right lung and left femur metastases were detected before
      nephrectomy. In the seventh week after nephrectomy, a partial jejunectomy was
      carried out because of the obstructive ileus caused by intraluminal multiple
      metastases of the jejunum. A pathological fracture of the metastasized right
      humerus occurred subsequently. After four months of intramuscular alpha
      interferon administration (3 x 10(6) units/day), however, x-rays revealed the
      complete disappearance of the metastatic lung shadow and a solid union of the
      humerus, and there were no tumor cells in the femur specimen resected at the
      subsequent reconstruction surgery of the left leg. Seven years have passed from
      onset, and the patient is still alive and disease free.

PMID- 8283793
TI  - Splenic abscess associated with colon cancer: a case report.
AB  - The present report describes a case of colon cancer which presented with a rare
      complication of splenic abscess. A 52-year-old Japanese man with diarrhea, fever
      and chills was admitted to our hospital. He complained of fever, with chills at
      night, and abdominal pain occurring during the last month. The origin of the
      fever was investigated, and Escherichia coli grew from a blood culture.
      Multilocular splenic abscesses and wall thickening of the descending colon were
      revealed by CT scan, magnetic resonance imaging and ultrasound. A cancer of the
      descending colon was found by barium enema and colonoscopy. A curative resection
      was performed and the pathological report revealed the splenic abscess to have
      developed from a direct extension of, and perforation by, the carcinoma of the
      descending colon.

PMID- 8283794
TI  - [Roles of department of laboratory medicine on the new patient clinic].
AB  - It is now quite well accepted that laboratory test results are indispensable or
      of primary significance to accurately diagnose a new patient's disease.
      Furthermore, most doctors recently find difficulty in appropriately selecting and
      ordering necessary but not excess laboratory tests and to read and interpret all
      the given test results correctly. In our hospital the system of the outpatient
      clinic will be changed basically on a specialty clinic system. In order to
      operate such a specialty clinic system effectively, it appears quite important to
      set up a unit to discriminate new unspecified patients properly and to consult
      them to an appropriate specialty clinic. As a preliminary trial, we opened a new
      patient clinic in July, 1992. The aim of this clinic is to accurately diagnose
      the new patients' disease immediately and to send them to the specialty clinic on
      the day of their first visit. Prior to history taking and physical examination by
      the attending doctor, the patients are instructed to take a set of laboratory
      tests. These include urinalysis, chest X-P, ECG, hematological examinations (RBC,
      WBC, Ht, Hb, PLT and ESR) and biochemical tests (AST, ALT, ALP, gamma GTP, LDH,
      CPK, Chol, T-Bil, TP, Alb, TG, BUN, Cr, Glu, Na, K, Ca, P and CRP). These results
      are transferred to the clinic within one hour so that the doctor is able to make
      the diagnosis effectively and to refer the patients to an appropriate
      clinic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283795
TI  - [Magnetoencephalography: its principles and clinical application].
AB  - This review attempts to provide the basis of neuromagnetism and its clinical
      applications. The progress in this field has been connected with the introduction
      of SQUID (superconducting quantum interference device) magnetometer which was
      produced by the progress of low temperature physics. A magnetic field is
      generated by an electric current in accordance with 'the right hand law', and the
      magnetic field pattern inevitably crosses orthogonally that of the electric
      field. A SQUID magnetometer is able to only detect the magnetic field which is
      generated by the current dipole orientated parallel to the skull surface.
      Magnetoencephalography (MEG) has several advantages compared to
      electroencephalography (EEG). One is its more excellent spatial resolution than
      that of EEG, and the other is a non-contact measurement, i. e., a noninvasive
      method. Therefore, MEG measurement could not interfere with sweating on the skull
      skin or a depolarization between skin and electrodes. This advantage allows it to
      record the magnetic field generated by the direct current potential in the
      cortical surface, and one example, that is, direct current magnetic fields evoked
      by slow potential changes in rat brain during asphyxia, are shown.

PMID- 8283796
TI  - [Recent advances in clinical application of event-related potentials].
AB  - Auditory and somatosensory ERPs were studied in patients with dementia of the
      Alzheimer type (DAT), those with vascular dementia and demented patients with
      idiopathic Parkinson disease. In both auditory and somatosensory modalities, the
      P3 latency in the demented patient group was significantly prolonged compared
      with the control data. However, comparisons of the P3 latency among the patients
      with DAT, vascular dementia and demented Parkinson did not reveal any significant
      differences. Patients with vascular dementia had significantly prolonged N140 and
      P200 latencies in somatosensory ERPs, whereas N1 and P2 latencies in auditory
      ERPs did not show any significant differences. Patients with acute onset
      hippocampal amnesia showed normal auditory P3 and somatosensory P3, whereas
      patients with diencephalic amnesia had prolonged auditory P3 and somatosensory P3
      in addition to the abnormal short latency somatosensory evoked potentials.
      Analysis of passively evoked P3 component and comparison between target P3 and
      passively evoked P3 may be useful for evaluation of demented patients with a
      variety of etiologies. Single-trial analysis showed a greater variance of P3
      latency in demented patients than in control subjects. A greater variance of P3
      resulted in 'absent P3' in conventional averaging in some of the demented
      patients. As vigilance levels changed from trial to trial, evaluation of P3
      latency variance has been proven to be useful.

PMID- 8283797
TI  - [Recent progress in Holter electrocardiography, focussed on heart rate
      variability].
AB  - Heart rate variability has attracted attention as an index of the effects of the
      autonomic nerve system on the heart rhythm. Heart rate variability (HRV) is low
      in patients at risk for sudden death. We evaluated the effects of caffeine, whole
      day work without sleep and drugs on HRV. Caffeine had no effects on HRV or
      ventricular extrasystoles in young adults but aggravated those in obese middle
      aged subjects. Whole-day work without sleep increased blood catecholamines and
      decreased HRV. These findings also suggest the usefulness of HRV as an index in
      health management. Tofisopam, enalapril and aprindine significantly improved HRV.
      These drug may be useful for maintaining normal autonomic nerve activity and
      preventing autonomic nerve diseases or sudden cardiac death in this stressful
      society.

PMID- 8283798
TI  - [DNA diagnostics of mycobacterial infection].
AB  - A diagnosis of mycobacterial infection may be suggested by a patient's symptoms,
      clinical or radiographic findings. However, the definite diagnoses of
      mycobacterial infections are dependent upon the isolation and identification of
      etiologic agents. Recently, nontuberculous mycobacteria are being increasingly
      recognized as the causes of lung diseases. Therefore, it is important to rapidly
      differentiate nontuberculous mycobacteria from Mycobacterium tuberculosis, since
      treatments, epidemiologic implications, and prognoses due to these various
      causative organisms may be considerably different. The isolation of mycobacteria
      from clinical samples takes several weeks for culture on presently available
      solid media, and biochemical identifications take additional several weeks after
      isolation of mycobacteria. Rapid, sensitive, and specific tests for detection of
      the organism as species in clinical specimens have been a long-standing goal.
      Recently, new diagnostic procedures based on molecular biology have been
      developed. The identifications of the species by DNA probes and PCR and a new
      test by means of luciferase reporter phages were discussed.

PMID- 8283799
TI  - [MRSA--detection of mecA and its regulatory genes].
AB  - Methicillin resistance in S.aureus and S.epidermidis strains is primarily due to
      production of a new penicillin-binding protein PBP2' with extremely low binding
      affinity to most beta-lactam antibiotics. The structural gene for PBP2', mecA, is
      detectable in clinical specimens by using the polymerase chain reaction (PCR).
      Amplified target DNA of 630bp can be resolved on ethidium bromide-stained gels,
      and hybridized with a probe conjugated to alkaline phosphatase. Survey for the
      mecA gene in 304 staphylococci revealed a good correlation between the presence
      of mecA and cultivation on agar plates with 4 micrograms/ml of oxacillin,
      although 3% of sensitive S. aureus strains had the mecA gene. On the other hand,
      analysis of the regulatory genes (orf 1 and 2) of methicillin resistance was
      performed on methicillin-resistant S.aureus strains N315 and MR108, demonstrating
      that the genome of MR108 lacks orf 2 which encodes the repressor protein
      (Hiramatsu et al., see Ref.5). The regulatory genes of mecA were surveyed for 192
      staphylococci by using PCR and allele-specific oligonucleotide probes: 76% of
      resistant S. aureus strains and 48% of resistant S. epidermidis strains possessed
      orf 1 corresponding to MR108 (constitutive-type strain), while the remainder of
      the resistant strains and two strains of sensitive S. epidermidis had two orfs of
      N315 (inducible-type strain). Furthermore, it appeared that mutation of the femA
      gene might not be an additional factor for expression of methicillin resistance.
      These observations suggest that mecA and its regulatory genes should be examined
      to understand how the genetic background contributed to the phenotypic expression
      of methicillin resistance in clinical strains.

PMID- 8283800
TI  - [HCV].
AB  - HCV is an RNA-virus which contains a positive-strand RNA genome. The RT-PCR
      method is used to detect the HCV-RNA in plasma. Quantification of HCV-RNA is
      difficult, but it can now be done by a competitive RT-PCR method developed
      recently. Genotypes of HCV can be classified into at least six basic groups,
      genotype I-IV can be distinguished by RT-PCR with type-specific primers. We
      report here that the prevalence of type-I, II, III, IV, and mixed type (II + IV)
      are 1.0%, 90.3%, 3.2%, 3.2%, and 2.2%, respectively. The DNA-probe method was
      recently developed and is less sensitive than the RT-PCR method, but simple and
      handy to detect HCV-RNA. Patients with chronic active hepatitis C received 3MU
      (9MU) of natural-interferon alpha (recombinant-interferon alpha 2a) daily for two
      weeks followed by three times a week for 22 weeks. Although the relationship
      between genotype of HCV and response to interferon-alpha therapy is unclear, the
      titer of HCV-RNA was significantly lower in long-term responders (ALT level
      remained within the normal range during the 12 weeks after the end of therapy)
      and short-term responders (ALT level rose again during the 12 weeks after the end
      of therapy) than that in nonresponders (ALT level was not normalized in spite of
      interferon-alpha therapy).

PMID- 8283801
TI  - [The diagnosis of HIV infection by detecting specific nucleotide sequence].
AB  - There are several methods to detect human immunodeficiency virus (HIV) infection;
      the detection of antibodies against HIV, the detection of HIV particles, and the
      detection of HIV infected cells. The detection of anti-HIV antibodies is
      practical, but the antibodies are undetectable both on a seronegative person at
      the superacute phase, and the new-born baby from a seropositive mother. No other
      method is ideal for all purposes. Thus the detection of the HIV-specific
      nucleotide sequence especially using the PCR method has been expected. We
      developed a quantitational PCR method to assay HIV-infected PBMC cell number, and
      the result correlated with that of the quantitational culture method, and also
      correlated with the CD4 count, that is inversely related to the clinical stage of
      HIV infection. Our quantitational PCR method must be improved before application
      to a practical routine test. A new PCR kit to detect HIV infected cells
      qualitatively has been developed and purchased in Europe. This kit is especially
      workable to test specimens where the antibody detection method cannot be used.
      PCR can be used on other specimens and can be applied to HIV infection. HIV RNA
      (both genomic RNA and viral mRNA) can be detected by a combination with the
      reverse transcriptase reaction. This method (RT-PCR) will be ideal to detect HIV
      particles. With PCR, the sequence-differentiation between each clinical virus
      strain may be detected, thus the characterization of a virus strain such as drug
      resistance, latency, or the prognosis may be recognized. PCR is indeed a valuable
      method to detect HIV-infection, provided its limits are properly understood.

PMID- 8283802
TI  - [General topics in abnormalities of lipoprotein metabolism].
AB  - Level of plasma cholesterol and triglycerides are regulated by a dynamic
      equilibrium between diet-derived exogenous supply and endogenous synthesis and
      degradation. The metabolism of lipoproteins such as chylomicron, VLDL, IDL, LDL
      and HDL, carrying cholesterol and triglycerides is regulated strictly by specific
      apoprotein constituents of these lipoprotein classes and its receptors. In
      addition, the metabolism of chylomicron and VLDL is also regulated by lipoprotein
      lipase on the surface of arterial wall. Current knowledge of the processes of
      lipid transport, such as cholesterol and triglycerides in the blood owes much to
      discoveries of major gene mutations affecting the apoproteins, key enzymes that
      control lipid transport, and cellular receptors that recognize specific
      apoproteins. It is, indeed, difficult to imagine how this field (lipoprotein
      metabolism) could have reached its present state in the absence of discoveries,
      which resulted from many clinical investigations of patients manifesting
      abnormalities of the plasma lipoproteins. General topics in lipoprotein
      metabolism and its abnormalities are summarized here.

PMID- 8283803
TI  - [Importance of primer selection in 5'NC region for the detection of hepatitis C
      virus RNA by polymerase chain reaction].
AB  - We compared two primer sets (A: 167bp, B: 269bp) derived from highly conserved
      domains within the 5' noncoding region (5'NC) of the hepatitis C virus (HCV)
      genome for their ability to detect HCV-RNA in a nested cDNA polymerase chain
      reaction assay (nested-PCR) in sera from 31 patients suspected of having HCV
      infection. Seventeen (54%) of 31 patients were positive for HCV-RNA with both
      primer sets. Using primer set A, 14(93%) of 15 samples with positive and 3(19%)
      of 16 samples with negative anti-HCV antibody test gave positive results for HCV
      RNA. With primer set B, 15(100%) of 15 antibody positive samples and 2(13%) of 16
      negative samples were positive for HCV-RNA. One antibody negative sample from a
      patient with alcoholic liver cirrhosis was positive for HCV-RNA only with primer
      set A. Another sample with positive antibody test, from a patient with chronic
      renal failure, was positive for HCV-RNA only with primer set B. A combination of
      more than one set of primers directed to the highly conserved 5'NC region, as
      well as proper selection of the exact nucleotide sequences, are important in
      improving the detection rate of HCV-RNA by PCR in serum of infected patients.

PMID- 8283804
TI  - [The states of recovery of blood counts and serum ferritin levels after blood
      donation].
AB  - Complete blood counts and levels of ferritin in serum (S-Fer) in 62 college
      students were analyzed continuously to clarify the effects of blood donation. In
      14 (45%) of 31 females, hemoglobin (Hb) and S-Fer levels showed decrease of more
      than 5% and 30%, respectively, four weeks after donation of 200ml or 400ml of
      blood. In 11 (35%) of the males and 6% of the females, Hb levels increased over
      5% during the same period. In 61% of the males and 45% of the females, S-Fer
      levels decreased. In only 19% of the males, the Hb and S-Fer levels were
      unchanged. Red blood cell (RBC) counts and Hb levels showed almost the same
      pattern. In 39% of the males and 48% of the females, the white blood cell (WBC)
      counts decreased more than 10%. In 10% of the males and 23% of the females, WBC
      counts increased more than 10% after blood donation. The WBC and RBC counts did
      not always show the same pattern of variation. After blood donation, the
      incidence of iron deficiency anemia among females increased from 13% to 23% and
      the incidence of latent iron deficiency among females increased from 10% to 42%.

PMID- 8283805
TI  - [Analyses of ventricular arrhythmias in patients with progressive systemic
      scleroderma (PSS) by ambulatory electrocardiography].
AB  - Disorder of cardiac conduction and automaticity have been widely reported in
      patients with progressive systemic scleroderma (PSS). In the present study,
      ventricular arrhythmias were monitored by 24-hour ambulatory electrocardiographic
      recording (Holter monitor) in 30 female patients with PSS and 20 apparently
      healthy female controls. The following results were obtained: 1) In the waking
      state, 8 cases of 30 patients showed grade III, IVA or IVB of ventricular
      arrhythmias, according to Lown's classification. On the other hand, ventricular
      arrhythmias, such as grade III, IVA or IVB, were not observed in the control
      group. 2) In the patient group, grade IVA arrhythmias were observed during
      defecation, driving or light working, and grade IVB were during defecation,
      urination, light working or sleeping. These results suggest that it is important
      to examine arrhythmias by Holter monitors in patients with PSS.

PMID- 8283806
TI  - [Immunopharmacological therapy of ulcerative colitis].

PMID- 8283807
TI  - [A clinical study of pepsinogen I and II producing gastric carcinomas].
AB  - Anti-human pepsinogen (PG) I and II monoclonal antibodies were used in an
      immunohistochemical study of 56 cases of gastric carcinoma (37 early stage and 19
      advanced stage). We examined the relationship between positivity of the carcinoma
      for producing PG I and II and serum PG I and II levels. We found that in 2 cases
      (3.6%), the carcinoma produced PG I and in 11 cases (19.6%), it produced PG II.
      Early gastric carcinomas and differentiated-type carcinomas produced PG II more
      frequently than advanced and undifferentiated-type carcinomas. Also, type II c
      carcinomas and carcinomas located in the C area of the stomach produced PG II
      more frequently. But there was no significant difference between PG I and II
      positive and negative cases in relation to both serum PG I and II levels.
      Moreover, the rate of positivity did not correlate with cases of abnormally high
      levels of serum PG I and II, (except in 1 case with abnormally high serum PG I in
      which PG II was produced.) These results suggest that there is no significant
      relationship between PG I or II-producing gastric carcinomas and serum PG levels.
      Furthermore, we examined PG II-producing and non-producing carcinomas in relation
      to the grade of inflammation, atrophy and intestinal metaplasia in gastric
      mucosa. However, there was no statistically significant difference among these
      factors. Only serum PG I and II levels were related to these parameters.

PMID- 8283808
TI  - [Relationship of Helicobacter pylori to chronological transition of endoscopic
      atrophic pattern].
AB  - The prevalence of Helicobacter pylori (HP) were studied in 117 subjects with no
      gross findings whose stomach age was equal to its chronological age. HP was
      detected by culture. The prevalence of HP significantly was higher in thirties
      and forties than other ages, and in C3 and O1 groups than other groups. Most of
      forties and fifties belonged to C3 or O1 groups. Histologically, HP infection was
      significantly frequent in the gastric mucosa with advancing inflammation. These
      findings suggest that HP infects in early middle age, causes the destruction and
      atrophy of gastric mucosa and disappears with ageing and chronological expansion
      of mucosal atrophy. We consider that HP infection may play a causative role of
      the aging process of the stomach.

PMID- 8283809
TI  - [A clinicopathologic study of primary gastric lymphoma of B-cell type among the
      Japanese with special reference to low-grade B-cell lymphoma of mucosa-associated
      lymphoid tissue (MALT)].
AB  - The most common primary site of low-grade B-cell lymphoma of mucosa-associated
      lymphoid tissue (MALT lymphoma) is the gastrointestinal tract, particularly the
      stomach. The relationship of MALT lymphomas, however, with the more commonly
      occurring large B-cell gastric lymphoma has not been directly discussed except in
      the report of Chan et al. (1990), which lacked clinical information regarding the
      behavior of these tumors. To elucidate the relationship between high-grade large
      cell lymphoma and MALT lymphoma, we studied in detail the histopathological and
      clinicopathologic features with the survival date of 77 Japanese cases of primary
      gastric lymphoma (PGL) of B-cell type. Based on degree of morphologically
      recognizable low- or high-grade components of the tumor, PGL was divided into
      four types: 18 cases of pure MALT lymphoma (type I); 13 cases of MALT lymphoma
      with small area of high-grade lymphoma (type II); 22 cases of high-grade lymphoma
      with small areas of MALT lymphoma (type III); and 24 cases pure high-grade
      lymphoma (type IV). Corresponding to the differences in the histologic pictures
      of each type, there were differences in the gross appearance, pathologic stage
      (including depth of invasion) and prognosis. These data suggests that both MALT
      and high-grade lymphomas of the stomach belong to the same cell lineage and
      constitute a pathological spectrum and that the histological grouping of PGL is
      clinico-pathologically useful.

PMID- 8283810
TI  - [The effects of synthetic protease inhibitor on motility of the human duodenal
      papilla].
AB  - We studied the effects of synthetic protease inhibitors on the motility of the
      human duodenal papilla. Before and after the intravenous administration of
      gabexate mesilate (GM) or nafamostat mesilate (NM), the duodenal papillary
      pressure was measured with a catheter tip pressure transducer under duodenoscopy.
      GM was administered to fourteen subjects at 1 and 3 mg/kg/h. The peak pressure
      and the basal pressure were dose-dependently reduced by GM, but the frequency did
      not change. The blood CCK concentration was not changed after GM administration.
      NM was administered to twelve subjects at 0.3 mg/kg/h. Both the papillary
      pressure and the frequency were not changed by NM. GM inhibited the papillary
      motility, but NM had no consistent effect on the papillary motility.

PMID- 8283811
TI  - [Inhibitory effect of portal pooling, bacterial translocation, and Kupffer cell
      activation on hepatic regeneration after partial hepatectomy by repeated portal
      triad cross clamping in rats].
AB  - Effect of hepatic ischemia and reperfusion on hepatic regeneration after 70%
      partial hepatectomy was evaluated in rats. Total hepatic ischemia by portal triad
      cross clamping (15 minutes) and reperfusion (15 minutes) was repeated two times
      during partial hepatectomy in the PS, non-PS, and G groups. In the C group,
      partial hepatectomy was made as a control without ischemia and reperfusion. In
      order to evaluate the effect of portal pooling, portal systemic shunt (PS shunt)
      was made by splenic transposition to subcutaneous space in the PS group, and
      compared with the non-PS group. Gadolinium chloride (GdCl3), the selective
      blocker of Kupffer (K) cell, was intravenously administered to the rat in the G
      group. Hepatic regeneration rates, labelling index of liver cells, rates of
      bacterial infection of mesenteric lymph nodes (MLN), blood levels of endotoxin
      (Ex) and tumor necrosis factor-alpha (TNF) were compared. Hepatic regeneration at
      28 days was suppressed by total hepatic ischemia in the non-PS group. Increased
      positive rates of MLN culture and blood levels of Ex showed bacterial
      translocation induced by the portal pooling during portal triad clamping. PS
      shunt reduced both bacterial translocation and the suppression of hepatic
      regeneration occurred in the PS group. Hepatic regeneration was not suppressed
      and blood TNF level did not increased in the G group by the inhibition of K cell
      function. In conclusion, repeated total hepatic ischemia and reperfusion induced
      portal pooling, bacterial translocation, and activated K cell, then inhibited
      hepatic regeneration after partial hepatectomy.

PMID- 8283812
TI  - [Relationship between gallbladder contractility and muscular fibrosis in the
      patients with cholecystolithiasis--immunohistochemical analysis].
AB  - The gallbladder muscular layers of the patients with cholecystolithiasis were
      examined to evaluate the relationship between the gallbladder contractility and
      fibrosis in the muscular layers. Gallbladder contractility decreased as the
      fibrosis of muscular layers became severe. The density of the antimacrophage (M
      phi) antibody positive cells in the muscular layers was apparently greater in the
      remarkable fibrosis group than in the unremarkable fibrosis group, and the
      density of the anti-TGF-beta antibody positive cells in the remarkable fibrosis
      group was significantly greater than in the unremarkable fibrosis group. Smooth
      muscle cells in the muscular layers had changed morphologically from a
      contractile type to a synthetic type, and fibroblasts were frequently observed in
      the muscular layers of the remarkable fibrosis group. Immunohistochemically, type
      III collagen was detected in the rough endoplasmic reticulum not only of
      fibroblasts but also of synthetic type-smooth muscle cells. These results suggest
      that the fibrosis in the muscular layers is one of the factors responsible for
      reduced gallbladder contractility in patients with cholecystolithiasis, and the
      increase of M phi, fibroblasts and synthetic type-smooth muscle cells is involved
      in such a fibrotic change of the gallbladder muscular layers.

PMID- 8283813
TI  - [Intraoperative real time observation of tumor blood flow in hepatocellular
      carcinoma by using color Doppler imaging].
AB  - To evaluate the tumor blood flow in hepatocellular carcinoma, we have introduced
      color Doppler imaging during operation. 37 hepatocellular carcinoma patient with
      54 nodules were included in this study. Following categories were analyzed, those
      were detectability of pulsatile blood flow and continuous blood flow signal in
      the tumor, pulsatile blood flow velocity depend on tumor size and pathological
      feature. Even the size of the tumor is less than 1 cm in diameter in 70% of those
      nodules we could detect and analyze the flow signal. This new modality could have
      a possibility to be a useful diagnostic device for small mass lesions in the
      liver.

PMID- 8283815
TI  - [A clinical study in 4 infants with duodenal ulcer].

PMID- 8283814
TI  - [Effect of KSG-504, a new synthetic cholecystokinin receptor antagonist on
      ethionine-induced acute pancreatitis in rats].
AB  - KSG-504, a new synthetic cholecystokinin (CCK) receptor antagonist derived from
      proglumide, has superior selectivity and affinity to CCK-A receptors. We have
      investigated the effect of KSG-504 on ethionine-induced acute pancreatitis in
      rats and the influence of endogenous CCK on evolution of pancreatitis and
      regeneration of pancreatic acinar cells. Reduction of pancreatic proteins and
      digestive enzyme contents was dose-dependently prevented by subcutaneous
      administration of KSG-504. The inhibition of evolution of pancreatitis was
      demonstrated histologically in KSG-504 treated rats. The effect of KSG-504 on
      pancreatic regeneration was evaluated by bromodeoxyuridine labeling index
      (B.L.I.) of acinar cells. There was no significant difference of B.L.I. between
      KSG-504 treated and non-treated rats. These results suggest that KSG-504 has a
      beneficial effect on ethionine-induced acute pancreatitis by blockade of
      endogenous CCK.

PMID- 8283816
TI  - [Rapid development of esophageal varices associated with primary biliary
      cirrhosis--report of two cases].

PMID- 8283817
TI  - [A case report of early primary biliary cirrhosis with bleeding esophageal
      varices].

PMID- 8283818
TI  - [A case of autoimmune hepatitis (lupoid-type) associated with positive
      anticentromere antibody and prevalent seroimmunological abnormalities in
      relatives].

PMID- 8283819
TI  - [Epithelial inclusion cyst of the gallbladder].

PMID- 8283820
TI  - [A case of ascariasis of the gall bladder with acute pancreatitis, diagnosed by
      ultrasonography].

PMID- 8283821
TI  - [Study of cases of mucin producing tumors of the pancreas showing penetration
      into other organs].

PMID- 8283822
TI  - Experimental model of carotid artery thrombosis in rats and the thrombolytic
      activity of YM866, a novel modified tissue-type plasminogen activator.
AB  - We compared the thrombolytic activity of a novel modified t-PA, YM866, with that
      of t-PA in a rat model of electrically-induced thrombosis. Histological
      examination revealed the thrombus to be composed mainly of platelet clumps.
      Measurement of the decrease in carotid blood flow showed that complete occlusion
      occurred within 14 min. At 10 min after the induction of thrombus, a test drug
      (YM866, t-PA, or saline) was administered by i.v. bolus injection under
      heparinization (300 IU/kg, i.v.). Both YM866 and t-PA exhibited dose-dependent
      thrombolytic activity; the reperfusion rate of YM866 was twice that of t-PA.
      There was no significant difference in time to reperfusion between the agents,
      but YM866 showed a greater improvement in patency status after successful
      thrombolysis than t-PA. Plasma fibrinogen fell slightly but significantly (14% of
      baseline value) in animals given 1 mg/kg of YM866. All groups of rats showed a
      significant decrease in carotid artery blood flow at 1 hr after successful
      reperfusion or injection of the drug, but this decrease showed significant
      recovery in animals given 1 mg/kg of YM866. These results suggest that YM866 by
      single bolus injection is a superior thrombolytic agent to t-PA, and that YM866
      can improve the patency status after successful thrombolysis. Furthermore, this
      platelet-rich thrombosis model permits continuous observation of the process of
      thrombus formation and subsequent thrombolysis and provides a useful tool for the
      screening and evaluation of efficacy of new antithrombotic agents.

PMID- 8283823
TI  - Sustained increase in adrenergic activity in gerbil striatum following transient
      ischemia.
AB  - We investigated the changes in striatal monoaminergic functions, focusing on the
      release and metabolism, in a cerebral ischemic model induced by a 5-min bilateral
      occlusion of the carotid arteries (BOCA) and reperfusion in anesthetized gerbils.
      In the microdialysis study, the striatal extracellular level of dopamine (DA)
      markedly increased (144-fold) immediately after BOCA. Although norepinephrine
      (NE) and 5-hydroxytryptamine (5-HT) could not be detected in the dialysates
      throughout the baseline period, they increased to detectable levels after BOCA.
      On the contrary, the tissue contents of NE and 5-HT decreased or tended to
      decrease up to 4 hr following reperfusion. Striatal DA contents did not show any
      changes in the early period after ischemia-reperfusion and slightly increased at
      4 hr or later. Tissue contents of 3-methoxytyramine (3-MT), a metabolite of DA by
      catechol-O-methyltransferase (COMT), increased 0 and 5 min after reperfusion.
      Normethanephrine (NMN), which is a metabolite of NE by COMT, also increased not
      only 5 min after but also up to 4 hr after ischemia-reperfusion, indicating a
      sustained increase in NE release. These results suggested that the neuronal
      activity of NE, which is supposed to exert a protective effect on ischemic
      damage, was enhanced for a longer period than that of DA after transient
      ischemia.

PMID- 8283824
TI  - Allergic bronchospasm and airway hyperreactivity in the guinea pig.
AB  - In passively sensitized guinea pigs, show infusion of an amount of ovalbumin
      insufficient to evoke airway obstruction induces hyperreactivity of the airways.
      A wide range of changed responsivity was observed for different test spasmogens,
      with leukotriene C4 > histamine > prostaglandin F2 alpha > bradykinin >
      leukotriene E4 > serotonin > acetylcholine. Injection of ovalbumin as a bolus
      produced pronounced airway obstruction without hyperreactivity. Airway
      obstruction due to vascular engorgement (dextran infusion) or edema (histamine
      infusion) did not result in hyperreactivity. Infusion of PAF induced pronounced
      airway obstruction together with hyperreactivity, but with a rank order of
      histamine > leukotriene C4 > serotonin > bradykinin > leukotriene E4 >
      acetylcholine. It can be concluded that allergic airway hyperreactivity in the
      guinea pig is spasmogen-selective and largely independent of airway obstruction.
      These observations question the presumption of non-selective hyperreactivity in
      allergic asthma and cast doubt upon the proposal that airway hyperreactivity is
      secondary to airway obstruction.

PMID- 8283825
TI  - Exacerbation of airway hyperreactivity by (+/-)salbutamol in sensitized guinea
      pig.
AB  - In guinea pigs passively sensitized to ovalbumin, sustained (6 days) subcutaneous
      infusion of (+/-)salbutamol (1 mg/kg/day) induced significant airway obstruction
      and heightened responsivity to airway spasmogens. Of these animals, a substantial
      proportion (78/235) were too responsive to injected spasmogens to permit infusion
      of ovalbumin or died following infusion of ovalbumin; yet there were few deaths
      (2/166) amongst the sensitized animals not exposed to (+/-)salbutamol. In
      comparison to the animals not exposed to (+/-)salbutamol, infusion of ovalbumin
      led to exaggerated responsivity of the airways to leukotriene C4, leukotriene E4,
      histamine, serotonin and acetylcholine, but not to prostaglandin F2 alpha or
      bradykinin. The capacity of sustained exposure to high doses of (+/-)salbutamol
      to induce airway hyperreactivity to allergic mediators may account for an
      association between asthma death and regular, excessive use of sympathomimetics.

PMID- 8283826
TI  - Calcium channel blocking properties of SM-6586 in rat heart and brain as assessed
      by radioligand binding assay.
AB  - The interaction of SM-6586 (methyl 1,4-dihydro-2,6-dimethyl-3-[3-(N-benzyl-N
      methyl-aminomethyl)-1,2,4- oxadiazolyl-5-yl]-4-(3-nitrophenyl)pyridine-5
      carboxylate) with the specific binding of 3H-PN200-110 to rat heart and brain
      membranes was characterized and compared with those of other Ca2+ antagonists.
      The blockade of 3H-PN200-110 binding sites induced by nifedipine, nitrendipine
      and nimodipine was reversed by washing, whereas the blockade by SM-6586 was not
      readily reversed under these conditions. No significant difference was found in
      irreversibility between SM-6586 enantiomers. When rat aortic strips were
      pretreated with SM-6586, the contractions induced by 50 mM KCl were inhibits even
      though SM-6586 was not present in the extracellular medium. This residual
      inhibitory effect was much stronger than that of nicardipine. The inhibition of
      KCl-induced contractions by nifedipine and nitrendipine was easily reversed by
      washing. Thus, we suggest that (+)SM-6586 is a novel 1,4-dihydropyridine
      derivative having a very slow rate of dissociation from the binding site. This
      property may explain its long-lasting antihypertensive effect.

PMID- 8283827
TI  - Contractile responses to histamine and GTP gamma S in beta-escin-treated skinned
      smooth muscle of guinea pig ileum.
AB  - To characterize the calcium (Ca2+)-releasing effects of histamine and GTP gamma
      S, the drug-induced tension developments were measured in beta-escin-treated
      skinned longitudinal smooth muscle of guinea pig ileum. Intracellular Ca2+ stores
      were loaded with Ca2+ by incubating the muscle for 10 min in a Ca(2+)-containing
      solution. Histamine (10-100 microM), applied after Ca(2+)-loading, produced a
      transient rise in tension. The effect of histamine was not preserved after
      treatment with 20 mM caffeine, a Ca(2+)-store releaser. The effect of histamine
      was potentiated by GTP; inhibited by GDP beta S, an antagonist of GTP for binding
      to G-proteins; or heparin, an antagonist of inositol 1,4,5-trisphosphate (IP3)
      for binding to its receptor; and mimicked by IP3. When GTP gamma S (20 microM)
      was applied and continued to be present for 15 min, a transient rise in tension
      followed by a small, sustained rise in tension was elicited. The effect of GTP
      gamma S was completely inhibited by GDP beta S. The initial, transient component
      of the biphasic GTP gamma S response was abolished or markedly inhibited after
      treatment with caffeine, heparin or the calcium ionophore A23187. The present
      results suggest that histamine and GTP gamma S cause a release of Ca2+ from
      caffeine-sensitive stores which is mediated by IP3 formed through a G-protein
      coupled mechanism. The GTP gamma S-induced Ca2+ release is not considered to
      involve such an IP3-independent process as described in chemically-skinned
      arterial muscle.

PMID- 8283828
TI  - Effects of D-Ala2-D-Leu5-enkephalin, microinjected into the supraoptic and
      paraventricular nuclei, on urine outflow rate.
AB  - The effects of D-Ala2-D-Leu5-enkephalin (DADL, a delta-opioid agonist),
      microinjected directly into the hypothalamic supraoptic (SON) and paraventricular
      (PVN) nuclei, on urine outflow rate, urinary osmotic pressure, blood pressure,
      heart rate, respiratory rate and rectal temperature were investigated in water
      loaded and ethanol-anesthetized rats. The microinjection of DADL into both the
      nuclei decreased urine outflow rate in a dose-dependent manner with an increase
      in urinary osmotic pressure, but did not change the other recorded parameters.
      The DADL-induced antidiuretic effect in the SON was inhibited by naloxone, but
      not by atropine, phenoxybenzamine, timolol nor a vasopressin antagonist, d(CH2)5
      D-Tyr(Et)VAVP. The effect in the PVN was inhibited by naloxone, atropine, timolol
      and d(CH2)5-D-Tyr(Et)VAVP, but not by phenoxybenzamine. These results suggest
      that DADL causes antidiuretic effects mediated through opioid receptors in both
      the SON and PVN, and the underlying mechanisms are different between them.
      Involvement of delta-opioid receptors in the DADL-induced antidiureses was
      discussed.

PMID- 8283829
TI  - Pharmacological profiles of aspergillomarasmines as endothelin converting enzyme
      inhibitors.
AB  - Aspergillomarasmine-A and -B (AM-A and -B), which were isolated from the cultured
      broth of an unidentified fungus N877, showed apparent inhibition against
      endothelin-converting enzyme (ECE) from bovine endothelial cells as measured by
      the formation of endothelin-1 (ET-1) converted from big endothelin-1 (bET-1),
      with IC50 values of 3.4 and 2.5 microM for AM-A and -B, respectively. EDTA also
      inhibited ECE (IC50 = 1.1 microM), but the inhibitions by AM-A, AM-B and EDTA
      were each abolished by the addition of 10 microM Zn2+ to the reaction mixture. In
      mice, AM-A and -B dose-dependently (10-50 mg/kg, i.v.) caused significant
      prolongation of the latency to sudden death induced by i.v. bET-1 (25 nmol/kg),
      but not that by ET-1 (5 nmol/kg), accompanied by a decrease in plasma
      immunoreactive ET-1 formation, while EDTA (24 mg/kg) failed to do so. In mice,
      the LD50 value of AM-A was calculated to be 159.8 mg/kg, i.v., which was much
      larger than that of EDTA (28.5 mg/kg, i.v.), indicating the low toxicity of AM-A.
      AM-A (30 mg/kg, i.v.) also suppressed bET-1-induced hemoconcentration and
      hypertension in mice and rats, respectively. These findings suggest that although
      ECE inhibition by AM-A was mainly attributable to its chelating activity, it
      showed apparent in vivo activities due to ECE inhibition with low toxicity.

PMID- 8283830
TI  - Induction of giant endothelial cells in culture by K-252a, a protein kinase
      inhibitor.
AB  - K-252a, a protein kinase inhibitor with a wide spectrum of activity, inhibited
      the serum-stimulated proliferation of cultured bovine carotid endothelial cells
      dose-dependently, and all the cells became remarkably large, with a diameter of
      more than 150 microns at K-252a concentrations of 0.3-1 microgram/ml. This effect
      of the agent was reproducible under the conditions described in this article.
      When the endothelial cells became abnormally large by K-252a, the surface area of
      the cell became wider, and the F-actin molecules increased in both number and
      length. Despite their abnormal size, K-252a-induced giant cells maintained at
      least three physiological functions characteristic to normal endothelial cells:
      1) ability to take up acetylated low density lipoprotein, 2) ability to produce
      and secrete endothelin and 3) ability to respond via an increase of [Ca2+]i to
      the stimulation by bradykinin. These observations suggest that K-252a-induced
      giant cells are useful tools for examining the function of endothelial cells
      because it is very reproducible and can be produced by an easy treatment.

PMID- 8283831
TI  - Prolonged administration of beta-alanyl-L-histidinato zinc prevents bone loss in
      ovariectomized rats.
AB  - The effect of beta-alanyl-L-histidinato zinc (AHZ), in which zinc is chelated to
      beta-alanyl-L-histidine, on bone metabolism was investigated in the femoral
      diaphysis of ovariectomized rats. AHZ (10, 30 and 100 mg/kg body weight/day) was
      orally administered to ovariectomized rats for 3 months. Ovariectomy
      significantly decreased the estradiol concentration in the serum as compared with
      that from sham-operated rats. This decrease was not altered by the dose of AHZ.
      The bone volume and dry weight in the femur of ovariectomized rats significantly
      decreased in comparison with those from sham-operated rats. Moreover, alkaline
      phosphatase activity, deoxyribonucleic acid (DNA) and calcium contents in the
      femoral diaphysis were significantly decreased by ovariectomy. The decreases of
      the femoral volume and dry weight, the femoral-diaphyseal alkaline phosphatase
      activity, DNA and calcium contents by ovariectomy were completely prevented by
      the tested doses of AHZ (10, 30 and 100 mg/kg/day). AHZ in the dose range of 10
      100 mg/kg/day caused a significant increase in zinc content in the femoral
      diaphysis of ovariectomized rats. The present study suggests that the prolonged
      administration of AHZ can prevent bone loss by ovariectomy.

PMID- 8283832
TI  - Comparison of the motor-stimulating action of EM523, an erythromycin derivative,
      and prostaglandin F2 alpha in conscious dogs.
AB  - The effect of EM523 [de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9
      hemiacetal], an erythromycin derivative, on gastrointestinal motility was
      investigated using conscious dogs in the fasting state, and it was compared with
      those of motilin and prostaglandin F2 alpha (PGF2 alpha). EM523 and motilin given
      as i.v. infusions induced strong contractions in the stomach that migrated along
      the intestine. On the other hand, PGF2 alpha stimulated intestinal contractions,
      but its effect on gastric motility was weak. EM523 had 1/50 the potency of
      motilin and 6 times the potency of PGF2 alpha for stimulation of intestinal
      motility. Atropine at 0.1 mg/kg, i.v. strongly inhibited gastrointestinal
      contractions induced by EM52 EM523 or motilin and partly inhibited PGF2 alpha
      induced intestinal motility. ICS-205-930, a 5HT3-receptor antagonist, at a dose
      of 1 mg/kg, i.v. strongly inhibited EM523 or motilin-induced gastric contractions
      but did not affect the action of PGF2 alpha. Infusion of EM523 at 100
      micrograms/kg/hr induced strong migrating contractions even when motility was
      depressed by dopamine infusion or laparotomy. Infusion of PGF2 alpha at 300
      micrograms/kg/hr stimulated intestinal but not gastric motility under these
      conditions. The results of this study indicate that the cholinergic pathway and
      5HT3 receptors are involved in EM523 and motilin-induced migrating
      gastrointestinal contractions, whereas the cholinergic pathway seems to be only
      partly involved in PGF2 alpha-induced intestinal contractions.

PMID- 8283833
TI  - Influence of transient global cerebral ischemia on the facilitatory modulation of
      the vagal baroreflex in dogs.
AB  - The influence of 5-min global cerebral ischemia on the facilitatory modulation of
      the vagal baroreflex through central alpha 2-adrenoceptors or by the electrical
      stimulation of the septum was investigated in anesthetized dogs. Reflex
      bradycardia was produced by a bolus injection of phenylephrine at a dose which
      produces about a 25-mmHg increase in mean blood pressure. The ischemia was
      produced by the occlusion of the brachiocephalic and the left subclavian arteries
      with preceding ligation of the intercostal arteries. Clonidine at 10 micrograms,
      administered intracisternally, decreased the blood pressure and heart rate and
      facilitated the vagal reflex bradycardia. During the reperfusion period following
      ischemia, however, clonidine failed to affect the reflex bradycardia. Electrical
      stimulation of the septal region facilitated the reflex bradycardia without
      marked influences on the basal blood pressure and heart rate. The facilitatory
      effect was dependent on the frequency (10 to 75 Hz) and amplitude (3 to 15 V) of
      stimulation and was not observed after vagotomy or ischemic insult. These results
      suggest that 5-min global cerebral ischemia may produce the dysfunction of the
      neurons which are closely related to the baroreflex loop and receive the
      facilitatory modulation through alpha 2-adrenoceptors and/or from the forebrain
      structures, leading to the dysfunction of the vagal baroreflex.

PMID- 8283834
TI  - Effect of naloxone on the morphine concentration in the central nervous system
      and plasma in rats.
AB  - We investigated whether the distribution (concentration) of morphine in the
      central nervous system (CNS) after systemic administration could be an index for
      the in vivo binding of morphine. Neither the morphine concentration nor its
      decline correlated with the density of opiate receptors. Naloxone decreased the
      morphine concentration in some CNS regions and plasma after a high dose of
      morphine, but not after a small dose of morphine. The CNS regions in which
      naloxone decreased the morphine concentration did not correlate with the density
      of opiate receptors, and the concentration ratios (CNS regions versus plasma) of
      morphine were not affected by naloxone. These results suggested that the morphine
      concentration in the CNS did not reflect the in vivo binding of morphine and that
      the naloxone-induced decrease in morphine concentration was not due to a
      displacement of morphine from its receptor sites but due to a change in morphine
      kinetics. Pharmacokinetic studies suggested that naloxone decreased the morphine
      concentration through an increased volume of morphine distribution. This naloxone
      induced decrease in morphine concentration may contribute to the naloxone-induced
      inhibition of morphine action in addition to the competitive antagonism at opiate
      receptors.

PMID- 8283835
TI  - Beneficial effect of a novel diuretic, M17055, on blood pressure and
      cardiovascular hypertrophy in spontaneously hypertensive rats.
AB  - We investigated the effects of a novel diuretic, M17055, on blood pressure and
      cardiovascular hypertrophy in spontaneously hypertensive rats (SHR). M17055 was
      orally administered once a day for 24 consecutive days to 14-week-old male SHR.
      M17055 at doses of 1.25, 2.5 and 5 mg/kg/day exerted a dose-related diuretic and
      antihypertensive effect during the treatment. The weight of the left ventricle
      normalized by body weight on the following day of the last dosage was
      significantly (P < 0.01) reduced by M17055 at doses of 2.5 and 5 mg/kg/day in a
      dose-dependent manner. The effect of M17055 on cardiac hypertrophy was more
      potent (P < 0.01) than that of captopril, when the comparison was performed at
      the doses of M17055 and captopril inducing the same extent of blood-pressure
      decrement. Vascular hypertrophy was evaluated by the media/lumen ratio (M/L) in
      the thoracic aorta and the first branch of the superior mesenteric artery. In the
      aorta, M/L was slightly, but not significantly, decreased by M17055 at doses of
      2.5 and 5 mg/kg/day, whereas it was decreased significantly (P < 0.01) by
      captopril. In the mesenteric artery, the ratio was significantly (P < 0.05)
      reduced by M17055 at a dose of 5 mg/kg/day. These results suggest that M17055
      possesses beneficial properties for the clinical treatment of hypertension.

PMID- 8283836
TI  - Multiple mediators and mechanisms are involved in the adaptive cytoprotection
      provided by certain mild irritants.
AB  - We investigated the participation of prostaglandins (PG) and nitric oxide (NO) in
      adaptive cytoprotection using 0.6 N HCl-induced gastric lesions in the rat
      stomach. Indomethacin reversed the protective effect of 0.2 N HCl more strongly
      than that of 0.35 N HCl, both of which markedly inhibited HCl ulcer. NG-Nitro-L
      arginine (L-NNA) did not affect the protective effect afforded by either 0.2 N
      HCl or 0.35 N HCl. Combined pretreatment with indomethacin and L-NNA did not
      diminish the protective action induced by 0.35 N HCl, but almost completely
      abolished the indomethacin-resistant protection afforded by 0.1 N NaOH. Acid mild
      irritant increased the gastric fluid volume concentration-dependently, whereas
      alkaline mild irritant had little or no effect on the volume. These results
      suggest that: 1) The mediators involved in adaptive cytoprotection afforded by
      0.1 N NaOH may be fully ascribed to PG and NO; 2) PG is a major mediator in the
      protection induced by 0.2 N HCl; 3) In the case of 0.35 N HCl, the mediators
      remain to be determined since increased gastric fluid volume could contribute to
      the protection through dilution. These findings thus may indicate that multiple
      mediators and mechanisms are implicated in adaptive cytoprotection.

PMID- 8283837
TI  - Effects of adenosine A1-agonist and -antagonist on urinary volume and Na
      excretion in IAP-treated and non-treated rats.
AB  - Effects of an adenosine A1-receptor agonist and antagonist were determined in
      pertussis toxin (IAP)-treated and non-treated rats. (-)-N6-(2-phenylisopropyl)
      adenosine, an adenosine A1-agonist, reduced the urine volume and sodium excretion
      without decreasing the glomerular filtration rate at 0.1 mg/kg (p.o.) in both IAP
      treated and non-treated rats. Diuretic effects of KW-3902 (8-(noradamantan-3-yl)
      1,3-dipropylxanthine) and 8-cyclopentyl-1,3-dipropylxanthine, adenosine A1
      receptor antagonists, were not affected by pretreatment with IAP. These results
      suggest that endogenous adenosine may induce antidiuretic effects by accelerating
      the reabsorption of water and sodium at tubular sites via an IAP-insensitive
      mechanism, and that the diuretic effects of the adenosine A1-receptor antagonist
      may result from inhibiting this action of endogenous adenosine.

PMID- 8283838
TI  - Effect of a new psychoactive compound, MCI-225, on brain monoamine metabolism in
      rats.
AB  - Effect of MCI-225 on brain monoamine metabolism was examined in rats. MCI-225 (30
      mg/kg, p.o.) had no influence on noradrenaline (NA) levels, but significantly
      inhibited the NA turnover in the hippocampus and hypothalamus. This compound also
      significantly increased the 5-hydroxyindoleacetic acid (5-HIAA)/5
      hydroxytryptamine ratio in the cerebral cortex, hippocampus and striatum; and it
      enhanced the probenecid-induced 5-HIAA accumulation in the striatum. In the
      microdialysis study, MCI-225 markedly increased the NA output, but decreased the
      3,4-dihydroxyphenylethyleneglycol output from the hypothalamus of urethane
      anesthetized rats. These results suggest that MCI-225 enhances both noradrenergic
      and serotonergic function by inhibiting NA uptake and accelerating 5-HT turnover,
      respectively.

PMID- 8283839
TI  - Inhibitory effects of KW-3902, a selective adenosine A1-receptor antagonist, on
      the adenosine-induced shortening of action potential duration in guinea pig
      atrial muscles.
AB  - We investigated the effects of KW-3902 (8-(noradamantan-3-yl)-1,3-
      dipropylxanthine), a newly-synthesized selective adenosine A1-receptor
      antagonist, on the shortening of action potential duration (APD) in guinea pig
      atria exposed to adenosine. The APD shortening by adenosine was inhibited by KW
      3902 at higher than 10(-8) M, but not by 10(-5) M of KF17837, an adenosine A2
      receptor antagonist. These results support the notion that the APD shortening by
      adenosine in atria is mediated via adenosine A1-receptors. The potency of KW-3902
      in antagonizing the APD-shortening were similar to those in antagonizing the
      negative inotropic and chronotropic action of adenosine in the isolated right
      atria, suggesting that these responses to adenosine are mediated via the
      receptors of the same type.

PMID- 8283840
TI  - [Middle weight molecules before and after detoxification in patients with
      peritonitis].
AB  - The dynamics of changes of the middle mass molecule (MMM) content in blood serum
      and peritoneal exudate was studied in 193 patients before and after different
      methods of detoxification: intraoperative cleansing of the abdominal cavity in
      closed treatment, planned stage cleansing in open treatment of peritonitis,
      hemosorption, therapeutic plasmapheresis, sorption through a pig spleen. The
      control group was made up of 88 donors and 16 patients with an urgent abdominal
      disease without signs of peritonitis. The diagnostic value of MMM and the
      expediency of combining surgical methods for cleansing of the abdominal cavity
      with methods of extracorporeal detoxification are shown.

PMID- 8283841
TI  - [Sorption in the treatment of acute peritonitis (experimental study)].
AB  - The data on the effective use of the new sorbent KAY and the carbon sorbent
      "Volna" in the treatment of acute generalized peritonitis were compared.
      Endosorption with sorbent KAY was conducted on an experimental model of
      generalized peritonitis. It produced a favorable effect on the functional
      morphology of the peritoneum by leveling many morphological signs of general
      intoxication of the organism and in this way creating the conditions for a
      favorable outcome of the postoperative period. The studies showed that the use of
      sorbent KAY in the treatment of acute generalized peritonitis facilitates active
      restoration of the function of vital organs, significantly raises the efficacy of
      treatment, and shortens the period of in-patient treatment.

PMID- 8283842
TI  - [Outcome of treatment of incarcerated hernia].
AB  - Experience in surgical treatment of 632 patients for incarcerated hernias of
      different localization is analysed. The patients' ages ranged from 39 to 91, 448
      (70.9%) patients were over 60 years of age. Inguinal and umbilical hernias were
      encountered most frequently--62.5%. The intestine was resected in 93 patients, 80
      of them were over 60 years of age (86%). Among these patients 63 were admitted to
      the clinic 1 to 4 days after the incarceration had occurred. The causes of late
      hospitalization: through the patient's fault in 80 (24.8%) cases, due to the
      doctor's errors in the prehospital stage in 39 (12.1%) cases. Kerte's method for
      determining the viability of the incarcerated intestine is subjective to a
      certain measure--the surgeons made errors in 14% of cases (confirmed
      histologically). The mortality was 13.4%, in 85% death occurred at an age over 70
      and in 74% of cases the patients were admitted 24 hours to 4 days after the
      incarceration. Incompetence of the sutures of the anastomosis (41%) was the main
      cause of death. Late hospitalization, elderly and old age, severe concomitant
      complications, and unwarrantably extended volume of the interventions were the
      main causes of unfavorable outcomes of the management of this category of
      patients.

PMID- 8283843
TI  - [Specifics in the diagnosis and surgical treatment of combined gastroduodenal
      ulcers].
AB  - The article deals with the experience in the treatment of 134 patients with
      concurrent gastroduodenal ulcers. The authors substantiate the necessity for
      performing early operative treatment by means of organ-preserving and organ
      sparing operation with consideration for the depth of the ulcerous defect.
      Attention is drawn to the need for operative correction of chronic duodenal
      obstruction. Two (1.5%) patients died after the operation. The late-term results
      were studied in follow-up periods of up to 10 years. Recurrences of peptic ulcer
      and syndromes of an operated on stomach requiring operative treatment were not
      encountered.

PMID- 8283844
TI  - [Surgical repair of large defects in the abdominal wall with biosynthetic
      prosthesis].
AB  - The article discusses the results of surgical management of postoperative and
      posttraumatic hernias with large defects in the anterior abdominal wall in 66
      patients. In 56 (80.2%) patients the defect in the abdominal wall measured more
      than 400 cm2 (20 cm in diameter). The authors developed a method for closure of
      the defect with a 2-3-layer biosynthetic prosthesis without reducing the volume
      of the abdominal cavity. The lower layer of the prosthesis is formed by a
      biological tissue which is covered in sequence with synthetic prostheses (layers)
      with an increasing destruction period. The authors claim that the method does not
      require prolonged preoperative management for the prevention of cardiopulmonary
      and gastrointestinal complications because it supposes maintenance of the optimal
      volume of the abdominal cavity. No complications on the part of the respiratory
      organs and disorders of gastrointestinal activity were encountered in the early
      postoperative period. Peripheral necrosis of the skin occurred in 7 patients,
      accumulation of serous fluid was encountered in 4 cases and a ligature fistula in
      one case. The late-term results were studied in 60 patients in follow-up periods
      of 12 months to 5 years. Recurrent hernias were not found.

PMID- 8283845
TI  - [Indications and contraindications to glomectomy in patients with bronchial
      asthma].
AB  - Thirty-year experience in surgical treatment of more than 3,000 patients with
      severe and moderately severe bronchial asthma showed that unilateral glomectomy
      produces a stable positive result in 69.5% of patients in follow-up repiods of
      two and more decades. Clinical recovery occurred in 23.2% of patients.
      Immunocorrection methods, such as hemosorption, plasmapheresis,
      plasmacytopheresis, xenosplenoperfusion, and the use of splenoperfusate raise the
      efficacy of the operation to 80-90%. The indications and contraindications for
      glomectomy in patients with bronchial asthma and methods for immunocorrection
      treatment of patients after glomectomy were developed.

PMID- 8283846
TI  - [Limb revascularization through the deep femoral artery in atherosclerotic
      femoropopliteal occlusions].
AB  - The article analyses the results of examination and surgical treatment of 101
      patients who were subjected to 105 reconstructive interventions on the deep
      femoral artery (DFA). Angiography showed affection of the orifice and beginning
      (up to 2 cm) of the DFA in 57.14% of cases, for a distance of 2-6 cm in 24.76%,
      and for a distance of more than 6 cm in 18.1% of cases. Arterial outflow was
      found to be excellent in 52.38%, good in 21.9%, satisfactory in 19.05%, and poor
      in 6.67% of cases. According to the findings of ultrasonic dopplerometry the
      changes of regional hemodynamics were most marked in III degree ischemia of the
      limb. Endarterectomy with the formation of a new communication between the
      superficial and deep femoral arteries was conducted in 14 cases, autovenous
      profundoplasty in 21, autoarterial profundoplasty in 35, autoarterial prosthetics
      of the DFA in 14, and autovenous DFA prosthetics in 21 cases. In 87.13% of
      patients the operation on the DFA was combined with lumbar sympathectomy. Choice
      of the method for DFA reconstruction on the basis of morphofunctional appraisal
      of the occlusive-stenotic process, the condition of collateral circulation and
      the outflow paths made it possible to achieve favorable results both in the
      immediate and late-term postoperative periods in more than 73% of cases.

PMID- 8283847
TI  - [Surgical treatment of patients with generalized atherosclerosis of the aorta and
      its branches].
AB  - The article analyses experience accumulated since September 1988 by the
      Department of Vascular Surgery based on Nizhny Novgorod Regional Clinical
      Hospital. The Department is equipped with apparatuses by means of which patients
      with generalized atherosclerotic lesions of the aorta and its branches can be
      examined to a full measure. The authors performed 287 operations on 205 patients
      with 3.9% mortality. The tactics of surgical treatment of patients with various
      atherosclerotic lesions of the aorta and its branches are analysed. It is
      concluded that multistage correction of the blood flow is most optimal in such
      patients.

PMID- 8283848
TI  - [Results of autologous venous femoropopliteal shunting].
AB  - The work deals with the comparative analysis of the results of femoropopliteal
      shunting (FPS) by means of the great saphenous vein (GSV) and arterialized
      lateral vein of the forearm (AVF). The results of operations with identical
      interventions but differing only in the graft are analysed. The best results of
      FPS with AVF are explained by adequate relationship of the graft and anastomosed
      artery in both anastomoses, as well as by adaptation of the wall of the AVF to
      the arterial blood flow during arterialization. In FPS by means of a reversed GSV
      the end of the graft of a lesser diameter is used for the proximal anastomosis
      and the end with the greater diameter--for the distal one. Spasm of the GSV after
      blood begins to flow into it is explained by the type reaction of the wall to the
      irritator.

PMID- 8283849
TI  - [Occlusion of pancreatic ducts in pancreonecrosis].
AB  - The article deals with the results of treatment of acute experimental necrosis of
      the pancreas by occlusion of its duct system with Adgenol. This led to authentic
      reduction of the level of trypsin, amylase, and middle mass molecules and
      improvement of the microhemocirculation parameters. The microscopic organization
      in the regional lymph nodes was normalized 3 hours after occlusion of the
      pancreatic ducts. The ultramicroscopic anatomy of the endothelial cells of the
      microvessels in the lymphatic sinuses was stabilized, leading to restoration of
      effective transendothelial transport. The method was used in 11 patients in the
      clinic. A good clinical effect was produced in 10 patients. There were no fatal
      outcomes.

PMID- 8283850
TI  - [Effect of C.P.Fedorov's approach on morphology and function of the anterior
      abdominal wall according to the findings of ultrasonic examination].
AB  - Echolocation was accomplished by means of "Alok-650" echochamber (Japan) and 3.5
      and 5 megahertz transducers. Twenty individuals of the control group and 40
      patients who underwent operations on the extrahepatic bile ducts and the
      gallbladder through S. P. Fedorov's approach were examined. Morphometry was
      conducted of the linea alba, the broad abdominal muscles, and the rectus
      abdominis muscles on 5 levels in relaxation and tension of the prelum abdominale
      muscles. The size of the rectus abdominis muscles in the control group was found
      to be the same on both sides. Atrophy of the right rectus abdominis muscle was
      revealed in all patients who were operated on. The spread and depth of the
      atrophic changes varied. In most cases the muscle was atrophied along its whole
      length distal to the line of division. The atrophic changes were maximum (22%-62%
      of the thickness of the symmetric area of the left rectus muscle) for a length of
      2-3 cm below the operative incision. In the zone with most marked atrophic
      changes the muscle loses its property of contraction in functional load of the
      prelum abdominale.

PMID- 8283851
TI  - [Hemorrhage from acute ulcers of gastric mucosa].
AB  - The work analyses the results of management of 429 patients with acute erosive
      ulcerative gastritis in a specialized department. The most frequent causes are
      duodeno- or enterogastric reflux (24.7%), abuse of alcohol (23.6%), medication
      with mucosa irritating drugs (22.5%). Particular attention is drawn to gastritis
      of a reflux character which is dangerous not only because of recurrent bleeding
      but also because of the possibility of structural reorganization of the gastric
      mucosa leading to development of carcinoma. Attention is focused on the errors in
      nonoperative and surgical treatment and the need for taking into consideration
      the etiopathogenesis of acute ulcers. In ulcerations of a reflux character it is
      recommended that after bleeding is arrested by conservative measures, an
      operation for removal of the reflux is performed in a planned order. In the other
      cases, in emergency situations, deep stitching of the erosions with vagotomy and
      pyloroplasty must be resorted to. The author considers acute ulcers of the
      stomach to be a precancer marker and believes it necessary to register all
      patients for regular medical control.

PMID- 8283852
TI  - [Diagnosis and treatment of complications of selective proximal vagotomy].
AB  - The authors analyse the causes of 170 (38.3%) complications which occurred after
      435 interventions for selective proximal vagotomy (SPV) with or without a stomach
      draining operation. Specific complications were encountered in 31.9% and
      unspecific complications in 7.0% of cases. Intraoperative complications happened
      in 6 (3.6%) patients who had complications after vagotomy, early complications-
      in 54 (31.5%), and late complications--in 79 (46.8%) patients. The main causes of
      the specific complications were technical faults in performing SPV, disorder of
      gastric secretory, motor-evacuation, and barrier activity due to incomplete,
      inadequate vagotomy. Inadequate drainage and disorders of the immune system and
      dietary regimen, gastroduodenal reflux are conducive to the development of
      complications after SPV. Reconstructive-restorative operations and resection of
      the stomach are the operations of choice in organic complications after SPV and
      produce good late-term results.

PMID- 8283853
TI  - [Glue endoscopic infiltration in the treatment of upper gastrointestinal
      hemorrhages].

PMID- 8283854
TI  - [Giant retroperitoneal soft fibroma].

PMID- 8283855
TI  - [Vascular neoplasms of the mediastinum].

PMID- 8283856
TI  - [Accessory pancreas in the wall of the stomach and duodenum].

PMID- 8283857
TI  - [Role of S.S. Iudin in the development of anesthesia in surgery].

PMID- 8283858
TI  - Credibility judgements of detectives: the impact of nonverbal behavior, social
      skills, and physical characteristics on impression formation.
AB  - Ninety-one detectives watched videofragments of 20 confederates who had been
      instructed either to tell the truth or to lie. After each videofragment the
      detectives indicated whether the confederate was lying. Although the study took
      place in a police context, and thus had higher ecological validity, the results
      strongly corresponded with those of previous studies: The accuracy rate was low
      (49%). Like the students in other deception studies, the detectives used the
      wrong cues to detect deception, and the actual situation (whether the
      confederates were telling the truth) did not predict suspiciousness.

PMID- 8283860
TI  - Effects of social bonds and childhood experiences on alcohol abuse and smoking.
AB  - Data from a national sample of 595 American adults were analyzed in an effort to
      evaluate simultaneously the potential effects of social bonds and childhood
      characteristics on smoking and alcohol use. Religious belief and belief in the
      importance of conformity with shared moral principles had significant negative
      effects on smoking, alcohol use, and alcohol abuse; commitment (satisfaction with
      one's socioeconomic status) inhibited smoking; and attachment (strong emotional
      bonds to family and friends) deterred alcohol abuse. Childhood trauma promoted
      both smoking and alcohol abuse.

PMID- 8283859
TI  - Acquaintance rape: the effect of race of defendant and race of victim on white
      juror decisions.
AB  - Racial bias appears to lead jurors in trials of stranger rape to convict Black
      defendants more readily and to sentence them more harshly than White defendants.
      It was hypothesized that jurors in an acquaintance rape case would demonstrate a
      different pattern of bias, based not only on the race of the defendant but also
      on the racial nature of the defendant-victim relationship. White American
      undergraduates read a trial transcript that established defendant-victim
      familiarity and sexual contact but was ambiguous about the victim's consent. Race
      of defendant and of victim (Black or White) were varied on a 2 x 2 design. The
      participants were asked to rate the guilt of the defendant and to recommend a
      sentence. Both Black and White defendants were rated as more guilty when the
      victim's race differed from their own.

PMID- 8283861
TI  - Social explanations and self-esteem in Northern Ireland.
AB  - The relationship between group-serving attributional biases and self-esteem among
      Catholics and Protestants in Northern Ireland was examined. There was little
      evidence of any consistently positive association between these variables.
      Differential patterns of group-serving biases were clearly evident. The Catholics
      demonstrated more pronounced levels of bias, whereas the Protestants tended to be
      more selective about the dimensions on which they displayed discrimination. These
      differential patterns of bias were consistent with each group's relative status
      position.

PMID- 8283862
TI  - Guilt and help from friends: variables related to healthy behavior.
AB  - American college students' self-reported status regarding 13 health-related
      behaviors, and several potential predictors of healthy behavior were assessed.
      Healthy behaviors were, at best, weakly related to being informed about or
      agreeing with a rule that the unhealthy alternatives were dangerous. Healthy
      behaviors were more strongly related to reports that guilty feelings would result
      from choosing the unhealthy alternatives and that friends would help with the
      healthy behaviors. Higher levels of reported self-control also predicted
      healthier behavior.

PMID- 8283863
TI  - The effect of the compliance strategy choice upon perception of power.
AB  - The relation between sequential request influence strategies and social power was
      examined, using a social impact theory model of perception. It was predicted that
      a door-in-the-face (DITF) scenario would suggest a greater difference in power
      between a giver and seeker than a foot-in-the-door (FITD) scenario would. Two
      judgment studies using American students at two different universities measured
      the perceived power of two individuals, the favor giver and the favor seeker, in
      either the DITF or the FITD. In both studies, the subjects perceived a
      significantly greater power difference between the giver and the seeker in the
      DITF strategy than they did in the FITD.

PMID- 8283864
TI  - Attributions of self-esteem as a function of duration of eye contact.
AB  - American male and female college students who were randomly assigned to one of
      six groups viewed a 60-s videotape. The content of the tape was derived from the
      factorial combination of sex of model (both American and White) on the tape with
      duration of eye contact (5 s, 30 s, or 50 s) maintained by the model with an
      interviewer. After viewing the tape, the subjects completed the Multidimensional
      Self-Esteem Inventory (O'Brien & Epstein, 1988) as they thought the model in the
      tape would. For all 10 self-esteem component scales, scores significantly
      increased as amount of eye contact increased. For 7 of the 10 scales, self-esteem
      scores for the female model were higher than those for the male model. The data
      generally extend and support previous research demonstrating that, as eye contact
      increases between Americans, American observers rate them more favorably.

PMID- 8283866
TI  - The relationship between parental interest and academic achievement of Xhosa
      children from monogamous and polygynous families.

PMID- 8283865
TI  - Fear of crime and the likelihood of victimization: a bi-ethnic comparison.
AB  - Fear of crime and the likelihood of future victimization for Hispanics and Blacks
      in the United States was examined. The sample size was 2,235 (1,696 Black and 539
      Hispanic respondents). Fear of crime and the likelihood of victimization were
      perceived as serious social problems by both Hispanics and Blacks, but Hispanics
      and women reported higher levels of fear of crime and felt more likely to be
      victimized than Blacks and men did.

PMID- 8283867
TI  - Differences in positive and negative connotations of nicknames and given names.

PMID- 8283868
TI  - Factor structure of employed adults' motivation for competitive or cooperative
      strategy.

PMID- 8283869
TI  - The measurement of emotional intensity from facial expressions.

PMID- 8283870
TI  - Perceived and ideal physiques in male and female university students.

PMID- 8283871
TI  - Treatment and prognosis in bronchial carcinoids involving regional lymph nodes.
AB  - From 1953 to 1992, 25 patients were surgically treated for bronchial carcinoids
      with metastases to regional lymph nodes (N1 or N2). The tumors were located
      centrally, involving main or lobar bronchi in 12 patients and were peripheral in
      13. Histologically, 12 of the carcinoids were classified as typical and 13 as
      atypical (neuroendocrine carcinoma). Pneumonectomy was performed in 11 patients,
      sleeve lobectomy in one, lobectomy in seven and bilobectomy in six. A formal
      mediastinal lymph node dissection was done in 20 patients. At final staging, 10
      had N1 disease and 15 had N2. No adjuvant treatment was given to the 10 patients
      with N1 disease. External radiation therapy was given after the operation to 9 of
      15 patients with N2 disease. The overall 5-year survival (Kaplan-Meier) was 75%
      (median 62 months). No difference in survival was found between patients with N1
      or N2 disease. However, survival and recurrence rate differed between typical and
      atypical carcinoids. In typical carcinoids, the 5-year survival was 92% and, in
      atypical carcinoids, it was 60% (p = 0.02). We conclude that complete resection
      for bronchial carcinoids results in long-term survival despite the presence of
      regional lymph node metastases. Recurrence appears to depend more on cell type
      than nodal status. Postoperative radiation therapy does not appear to be
      beneficial.

PMID- 8283872
TI  - Supravalvular aortic stenosis. Long-term results of surgical treatment.
AB  - To determine long-term outcome after operation for supravalvular aortic stenosis,
      we reviewed the case histories of 80 patients who had repair of the localized
      form (group A) (n = 67) or diffuse form (group B) (n = 13) from 1956 to 1992,
      including 31 patients with the Williams-Beuren syndrome. Ages ranged from 7
      months to 54 years (mean = 12.6 years). Forty-six patients had one or more
      associated cardiovascular anomalies; the most common was aortic valve stenosis
      (33.8%). Eighteen patients had 22 previous cardiovascular operations, and 28
      patients had one or more additional anomalies repaired during their initial
      procedure at our institution. In group A, the aortic root was enlarged with a
      teardrop-shaped patch (n = 61) or a pantaloon-shaped patch (n = 6). In group B,
      patch enlargement of the aorta was confined to the root (n = 4) or extended into
      the ascending aorta or aortic arch (n = 7); one patient had a graft placed
      between the ascending and descending thoracic aorta and one patient had a left
      ventricular-aortic conduit. There were no deaths in group A; two patients in
      group B in whom patch enlargement was confined to the aortic root died during the
      operation (2.5%). Follow-up extended to 33.4 years (mean = 14.2 years); there
      were five late deaths in group A and one in group B. Survival excluding operative
      mortality was 94% at 10 years and 91% at 20 years. All patients were in
      functional class I or II. There was no significant difference between patients
      with a teardrop-shaped or pantaloon-shaped patch in terms of late gradient,
      survival, or aortic insufficiency. By Cox multivariate model, the only
      independent predictor of late death for all patients was associated aortic valve
      disease (p = 0.02), which was also a risk factor for late reoperation (p = 0.02).
      In group B, overall survival was better in patients who received an extended
      patch versus aortic root patch only (p = 0.02). We reached the following
      conclusions: (1) Associated aortic valve disease was strongly correlated with
      late death and need for reoperation. (2) Both the teardrop-shaped and pantaloon
      shaped patch techniques provide excellent long-term relief of localized
      supravalvular gradients and preservation of aortic valve competence. (3) In
      diffuse supravalvular aortic stenosis, aortic enlargement should be extended into
      the ascending aorta or beyond as required to relieve the gradient; some patients
      may require a graft or conduit.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8283873
TI  - High-dose steroids prevent placental dysfunction after fetal cardiac bypass.
AB  - Surgical treatment of certain congenital heart lesions in utero may have a
      therapeutic advantage over postnatal repair or palliation. For fetal heart
      surgery to be possible, a method to support the fetal circulation is necessary.
      Early experimental attempts at fetal cardiac bypass were unsuccessful because of
      increased placental vascular resistance during and after fetal cardiac bypass,
      which led to decreased placental flow, fetal asphyxia, and death. Our laboratory
      has demonstrated that the administration of indomethacin (a cyclooxygenase
      inhibitor) during fetal cardiac bypass prevents this increase in placental
      vascular resistance during and after fetal cardiac bypass. The specific mechanism
      by which indomethacin achieves this effect is likely to be either by inhibiting
      the production of a placental vasoconstrictive prostaglandin or by diverting
      substrate from the cyclooxygenase pathway to the lipoxygenase pathway, thereby
      potentially increasing the production of a placental vasodilating leukotriene. To
      examine these potential mechanisms in more detail, we inhibited both
      prostaglandin and leukotriene synthesis at the phospholipase stage with high-dose
      steroids. Fourteen fetal lambs were used in the study. Six animals received
      indomethacin (3 mg/kg), four received high-dose steroids (Solu-Medrol 50 mg/kg),
      and four animals were used as controls. Observations were made during a 1-hour
      prebypass period, a 30-minute bypass period, and a 2-hour postbypass period.
      Placental blood flow and placental vascular resistance were calculated at four
      times during the experiments: before sternotomy; after sternotomy; during bypass
      at 30 minutes; and 30 minutes after cessation of bypass. Similar to indomethacin,
      high-dose steroid administration during fetal cardiac bypass prevents the rise in
      placental vascular resistance and preserves placental blood flow during and after
      fetal cardiac bypass. This study suggests that the production of a placental
      vasoconstrictive prostaglandin is responsible for the increase in placental
      vascular resistance and decrease in placental blood flow observed after fetal
      cardiac bypass.

PMID- 8283874
TI  - Risk of replacement of descending aorta with a standardized left heart bypass
      technique.
AB  - Replacement of the descending aorta for aneurysms (51%) and dissection (49%) was
      performed in 132 patients with a highly standardized left heart vortex-pump
      bypass. No adjuncts other than staged aortic clamping and intercostal artery
      reconnection were used to reduce spinal cord injury in extensive involvement.
      Four patients (3%) died early, two of cardiac cause, and nine (7%) died late.
      Complications of vital organ function occurred in eight patients, two having
      reversible renal failure and six spinal cord injury that was permanent in three
      (2.3%). Cord injury occurred only in replacement beyond thoracic segment 8 and
      could not be completely avoided despite distal intercostal artery reconnection in
      two cases; in the other four cases such vessels either did not appear worth
      reconnecting or were sacrificed in emergency operations. We conclude that left
      heart bypass effectively unloads the proximal circulation during aortic occlusion
      while maintaining adequate perfusion of distal vital organs as evidenced by low
      rates of early mortality and renal failure. The remaining risk of spinal cord
      damage may be lowered by more aggressive reconnection of all distal intercostal
      arteries and by extending the permissible cord ischemic period by means of
      hypothermia.

PMID- 8283875
TI  - Tracheal sleeve pneumonectomy for bronchogenic carcinoma.
AB  - For a long time, primary tumors arising less than 2 cm distal to the carina have
      presented a contraindication to surgical excision. Tracheal sleeve pneumonectomy
      technique allows carinal resection and reconstruction but still carries
      considerable postoperative complications. From 1983 to 1992 we performed 27 right
      tracheal sleeve pneumonectomies and one left. Fourteen patients had N0 nodes,
      nine had N1, and five had N2. No anastomotic complications, either fistula or
      stenosis, were observed. Successful outcome depends on meticulous attention to
      surgical details and careful anaesthetic management with a new ventilation tube.
      One patient died on the twenty-second postoperative day from myocardial
      infarction. Complications included pneumonia (one), vocal cord paresis (two), and
      pleural empyema without bronchial fistula (one). Conservative treatment allowed
      complete recovery from all complications. There are seven patients alive at 4
      years after operation and one at 5 years. Six patients have been disease-free for
      between 1 and 32 months. Two patients died free of disease at 13 and 42 months.
      Two patients died of mediastinal recurrence and 10 of distant metastases within 6
      and 54 months.

PMID- 8283876
TI  - Surgical treatment of thoracoabdominal aortic aneurysms by simple crossclamping.
      Risk factors and late results.
AB  - Between 1981 and 1987, 88 consecutive patients were operated on for a
      thoracoabdominal aortic aneurysm by simple crossclamping and a graft inclusion
      technique (without shunts or heparin). This article presents an analysis of the
      operative outcome and long-term follow-up. Patient- and operation-related
      variables are age (mean 64.3 years, range 28 to 82 years), sex (82% men), rupture
      (20.5%), diabetes (2.3%), renal insufficiency (34.1%), chronic obstructive
      pulmonary disease (27.3%), previous aortic operation (31.8%), arterial
      hypertension (66%), postdissection (18.2%) versus degenerative (80.7%) origin,
      preoperative shock (11.4%), ischemic cerebrovascular (12.5%) or ischemic heart
      (17%) disease, peripheral vascular disease (14.8%), renal (mean 48 minutes, range
      0 to 83 minutes) and lower spinal cord (mean 21 minutes, range 0 to 68 minutes)
      ischemic time, number of reattached intercostals, blood loss, and extent of the
      aneurysm (Crawford classification: type I, 16 patients [18.2%]; type II, 21
      patients [23.8%]; type III, 29 patients [33%]; and type IV, 22 patients [25%].
      Intraoperative mortality is 1.1% (n = 1). Thirty-day mortality is 5.9% (n = 5).
      Hospital mortality is 11.4% (n = 10): 7% for elective cases and 28% for ruptured
      aneurysms (p = 0.014). The survival at 2 years is 78% +/- (4.4%) and at 5 years
      54% +/- (5.3%). Postoperative spinal cord injury occurred in 12 patients (13.8%)
      (5 had paraplegia and 7 had paraparesis) and postoperative renal dysfunction
      necessitating dialysis in 12 patients (14.1%). Risk stratification for hospital
      death, late death, renal failure, and spinal cord dysfunction was performed by
      means of multivariate logistic regression and Cox proportional hazard regression
      as appropriate. The best fitting model to predict hospital death includes
      preoperative shock (p = 0.02), female sex (p = 0.06), preoperative elevated serum
      creatinine level (p = 0.06), and preoperative myocardial infarction (p = 0.08).
      Variables predictive for late death are postoperative dialysis (p = 0.002), age
      (p = 0.008), and rupture (p = 0.04). The risk factors of postoperative dialysis
      are age (p = 0.003) and preoperative serum creatinine level (p = 0.04). The risk
      of postoperative spinal cord dysfunction increases with longer lower spinal cord
      ischemic time (p = 0.02) and with the presence of preoperative shock (p = 0.06).

PMID- 8283877
TI  - Long-term results of mitral valve reconstruction for regurgitation of the
      myxomatous mitral valve.
AB  - The myxomatous, degenerated, prolapsed or "floppy" mitral valve is the most
      common cause of mitral regurgitation in North America. Mitral valve
      reconstruction for mitral regurgitation was carried out in 219 consecutive
      patients with a myxomatous mitral valve from 1984 to 1993. Of the 139 men and 80
      women, 23 to 84 years of age (mean 63 years), 36% of patients were 70 years of
      age or older, 77% were in New York Heart Association functional class III or IV,
      and 29% had coronary artery disease necessitating coronary bypass. The most
      common operation was posterior leaflet resection (161 patients [73%]). The
      anterior leaflet was resected in 14 patients, and both the anterior and posterior
      leaflets were resected in 15 patients. A variety of other techniques were used,
      including commissuroplasty and use of annuloplasty rings. A flexible Duran ring
      was used in 111 patients (51%), a Carpentier-Edwards ring in 44 patients (20%),
      and no ring was used in 64 patients (29%). Five operative deaths occurred (2.3%);
      four of the five deaths occurred in patients 70 years of age or older (5.1%); and
      one in 141 patients (0.7%) was younger than 70 years of age. In the late
      postoperative period (mean follow-up 2 years), 90% of patients had no symptoms,
      two had endocarditis, and seven patients had thromboemboli (transient in four,
      permanent in three). Structural valve degeneration requiring reoperation occurred
      late in 12 patients; eight were in posterior leaflet resection and two in
      anterior or anterior and posterior; six of 12 had no annuloplasty ring. The
      incidence of structural valve degeneration was less than 5% from 1990 to 1993. No
      systolic anterior motion of the mitral valve was seen with postoperative
      echocardiography before discharge. Actuarial analysis at 5 years for overall
      survival was 86% +/- 5%, freedom from infectious valve degeneration 97% +/- 2%,
      and freedom from thromboembolism 94% +/- 3%. Freedom from structural valve
      degeneration overall was 83% +/- 4%, with a flexible ring it was 89% +/- 6%, with
      a rigid ring it was 88% +/- 6%, and with no ring it was 67% +/- 12% (p = 0.03).
      Mitral valve reconstruction for complicated myxomatous disease of the mitral
      valve, regardless of leaflet involvement, is feasible and offers excellent early
      and late results.

PMID- 8283878
TI  - The use of unstented homograft valves for aortic valve reoperations. Review of a
      twenty-three-year experience.
AB  - Unstented homograft valves offer several theoretical advantages when used for
      patients who have had previous operations on the aortic valve. Between January
      1970 and February 1993, 177 patients received unstented homograft valves after
      previous aortic valve operations. One hundred thirty-four patients had previous
      aortic valve replacement in the form of homografts (101 patients), mechanical
      prostheses (24 patients), and bioprostheses (9 patients), and 43 had previous
      valve repair. The indication for reoperation was deterioration of a noninfected
      valve (124 patients), infective endocarditis (40 patients), and failure of a
      noninfected mechanical valve (12 patients). Fresh homograft valves were implanted
      in 60 patients, homografts preserved in antibiotics were used in 111 patients,
      and 6 patients received cryopreserved valves. Aortic valve and root replacement
      was performed in 60 patients, and in 117 the homograft was inserted freehand in
      the subcoronary position. The early mortality was 5.1%. The actuarial survival at
      10 years was 71%. Multivariate analysis demonstrated that patients with previous
      homograft replacement have a better long-term survival than patients who had
      previous mechanical valves (p = 0.017). The freedom from valve-related death and
      reoperation was 70% at 10 years. Fresh homografts faired better than antibiotic
      sterilized homografts (p = 0.007). None of the patients had recurrence of
      endocarditis at 6 months, although 1 patient died of uncontrolled infection
      despite valve replacement. The freedom from recurrent endocarditis was 88% at 10
      years. We conclude that unstented aortic homografts provide good early and long
      term results for aortic valve reoperations, particularly in patients with
      previous homograft replacement. Recurrent endocarditis is uncommon even in
      patients operated on for prosthetic valve infections.

PMID- 8283879
TI  - Aortic root and valve relationships. Impact on surgical repair.
AB  - A surgical procedure has recently been described for patients with aortic
      incompetence caused by annular dilation, but with normal aortic leaflets. The
      dilated aortic root is replaced with a Dacron graft, and the native aortic valve
      is resuspended within the graft. Matching the size and shape of the graft to the
      size of the leaflets may have significant effects on valve closure and leaflet
      stress and thus on the longevity of the repair. To define the relationship of
      native aortic root structure to leaflet size, we morphologically examined normal
      human aortic roots (n = 10) and valve leaflets and applied mathematic analyses to
      the results. Our data show that the root has a consistent shape with varying size
      and that there is a definable mathematic relationship between root diameter and
      clinically measurable leaflet dimensions. We derived an equation that allows
      calculation of the appropriate diameter of the root at the sinus of Valsalva
      level from leaflet heights and perimeters. The diameter of the graft at the
      sinotubular junction and base should follow the relationship of the normalized
      root dimensions, either by tailoring of the graft or by new graft design. The
      current data imply that the graft should incorporate sinuses for proper valve
      closure and for sharing stress with the leaflets. Application of these results
      will allow prosthetic graft design to more closely resemble the native aorta.
      These new grafts should improve physiologic function of the valve, reduce leaflet
      stress, and increase the durability of the repair.

PMID- 8283880
TI  - Surgical treatment of active infective endocarditis with paravalvular
      involvement.
AB  - Aortic root infection remains a challenging problem in the surgical treatment of
      both native and prosthetic valve endocarditis. Between 1980 and 1991, 73 patients
      with active aortic valve endocarditis and paravalvular infection underwent
      operation. Indications for operation included congestive heart failure and
      uncontrolled sepsis. Aortic root abscesses were located in the noncoronary anulus
      or in the aorticomitral junction in 45% of cases, followed by the subannular
      interventricular septum in 23%. Two patients had an aorticoatrial fistula, seven
      an interventricular septal defect. Total or partial left ventricular-aortic
      dehiscence was observed in 27 patients. All patients underwent aortic valve
      replacement, nine with simultaneous mitral valve operations. Two of the latter
      required patch reconstruction of the destroyed aorticomitral septum with double
      valve replacement. Reconstruction of the aortic base was possible in 16 patients,
      whereas in 12 total replacement of the aortic root was necessary. In one patient,
      supracoronary aortic valve replacement was used. Recently, topical application of
      antibiotics in fibrin sealant was used in 25 patients. The operative mortality
      rate was 21% and correlated to preoperative uncontrolled sepsis and the presence
      of extensive root destruction. Operation for active endocarditis of the aortic
      root requires radical, individualized techniques and results in an acceptable
      operative and long-term risk. The use of an antibiotic fibrin compound appears to
      be a useful prophylactic tool to prevent postoperative residual endocarditis.

PMID- 8283881
TI  - Hemodynamic assessment during exercise after left ventricular aneurysmectomy.
AB  - The exercise hemodynamics of eight patients who underwent cardiac catheterization
      were assessed at rest and during exercise, before and after left ventricular
      aneurysmectomy by the classical technique. Left ventricular end-diastolic volume
      increased before operation and then significantly decreased after the operation
      (p < 0.05). The ejection fraction increased from 0.27 before the operation to
      0.46 after the operation (p < 0.01). The cardiac index, which was low before
      operation, increased within the normal range after operation. Mean systolic
      circumferential tension also decreased significantly (p < 0.01) after the
      operation. Thus, the indexes at rest showed improvement. Left ventricular end
      diastolic pressure showed a decreasing tendency after the operation both at rest
      and during exercise in comparison with that before the operation. However, the
      difference was not significant. The stroke work index increased significantly
      during exercise after the operation (p < 0.05). Before the operation, the stroke
      work index did not increase despite the elevation of left ventricular end
      diastolic pressure; however, after the operation, the stroke work index increased
      during exercise without much increase of left ventricular end-diastolic pressure.
      This indicated improvement in the Frank-Starling curve and recovery of preload
      reserve by the resection of the left ventricular aneurysm. Thus, an important
      factor for demonstrating improvement in postoperative cardiac function was
      clarified through its relation to exercise load.

PMID- 8283882
TI  - Cardiac echinococcosis. Surgical treatment and results.
AB  - During the last 15 years, eight patients with a diagnosis of hydatid cysts of the
      heart and one patient with a diagnosis of alveolar hydatid disease with
      intracardiac parasitic thrombus underwent successful operation at La Pitie
      Hospital. Only five cases had symptoms, and the remaining four cases were
      diagnosed incidentally. Serologic tests achieved a variety of results and were
      not determinant. All patients were examined with echocardiography and
      angiography, and almost all patients underwent magnetic resonance scanning.
      Sternotomy was the approach used, and all patients underwent operation with
      cardiopulmonary bypass. Surgical treatment included puncture and aspiration of
      the cyst content, previous sterilization with hypertonic saline solution, and
      excision of the cyst with closure of the cavity in seven patients with different
      concomitant procedures. No case of intraoperative rupture was reported, and the
      only complication was an atrioventricular block in a patient with a cyst of the
      left ventricular wall invading the intraventricular septum. There was no
      operative mortality, and only one late death was observed. No recurrences or
      associated complications were reported in the late follow-up.

PMID- 8283883
TI  - Surgical management of non-small-cell lung cancer with ipsilateral mediastinal
      node metastasis (N2 disease).
AB  - Between 1979 and 1989, 876 patients with non-small-cell lung carcinoma were
      referred to our unit for surgical treatment. One hundred forty-six patients were
      judged not suitable for surgical treatment on clinical, radiologic, or
      bronchoscopic findings. Cervical mediastinoscopy or anterior mediastinotomy (or
      both) showed that 151 patients had mediastinal involvement by invasion or
      metastases into the ipsilateral (N2 disease) or contralateral (N3 disease)
      superior mediastinal lymph nodes and were therefore deemed inoperable. Except for
      one patient who had involvement of a single nodal station at mediastinoscopy, all
      other patients (n = 578) undergoing thoracotomy were thought, on the basis of
      computed tomographic scan or mediastinal exploration (or both) not to have N2
      disease. Despite our efforts to avoid surgery on patients with N2 disease, at
      thoracotomy routine mediastinal node dissection disclosed that 149 patients had
      unsuspected N2 disease. Resection was possible in 130 (87.3%) by pneumonectomy (n
      = 72), bilobectomy (n = 7), lobectomy (n = 49), or lesser resection (n = 2). In
      three patients the resection was incomplete (2.3%), but in 127 a complete
      resection was performed (85%). Histologic examination in these 149 patients
      showed that 72 tumors were squamous cell carcinoma, 54 adenocarcinoma, 14 large
      cell carcinoma, and 9 of mixed type. Eight patients died in the hospital after
      thoracotomy. Adjuvant therapy was not used after complete resection. Complete
      follow-up was obtained in 134 patients and the mean follow-up period was 27.25
      months (1 to 116 months). The actuarial 5-year survival for those having complete
      resection was 20.1%. There was a statistically significant difference favoring
      long-term survival in those patients with squamous cell carcinoma (p < 0.01) and
      those in whom only one nodal station was involved (p < 0.05). Neither the extent
      of resection nor the involvement of any specific nodal station influenced long
      term survival. Despite rigorous preoperative investigations, routine mediastinal
      node dissection demonstrated mediastinal node metastasis for the first time at
      thoracotomy in 26% of our patients. We believe resection is justified in these
      patients, who have already necessarily incurred the morbidity and mortality of
      thoracotomy, so long as complete resection is possible.

PMID- 8283884
TI  - Experimental study of a new sutureless intraluminal graft with a shape-memory
      alloy ring.
AB  - A new sutureless intraluminal graft has been developed with a ring made of a
      titanium-nickel shape-memory alloy. The diameter of the ring can be reversibly
      reduced by compression in 4 degrees C normal saline solution and recovers its
      original shape in 38 degrees C physiologic saline solution during insertion in
      the aorta. The new graft was implanted in nine dogs and was evaluated
      histologically and angiographically at various intervals from 15 to 90 days. No
      complications, such as dislodgment, aortic rupture, stenosis, or aneurysmal
      dilation, were observed. The component of the shape-memory ring allows the graft
      to be introduced and secured in place easily. The function of this ring is better
      than that of the rigid ring.

PMID- 8283885
TI  - Risk factors for operative mortality and sternal wound infection in bilateral
      internal mammary artery grafting.
AB  - To investigate risk factors for operative mortality and sternal infection in
      patients undergoing bilateral internal mammary artery grafting, we analyzed the
      data of 199 patients who underwent this procedure from January 1986 through June
      1992. These patients were also compared with those who underwent only saphenous
      vein grafting (1664 cases) and those who underwent unilateral internal mammary
      artery grafting (3359 cases) during the same time frame. The operative mortality
      was 3.52% (7/199) in the patients having bilateral internal mammary artery
      grafting, 2.71% (91/3359) in those having unilateral internal mammary artery
      grafting, and 8.53% (142/1664) in the patients having saphenous vein grafting (p
      < 0.0001). The occurrence rate of sternal infections was 2.45% (5/199) for
      bilateral internal mammary artery grafting, 1.32% (13/1664) for saphenous vein
      grafting, and 1.19% (20/3359) for unilateral internal mammary artery grafting (p
      = 0.27). The univariate analysis revealed that age, history of congestive heart
      failure, emergency operation, ejection fraction, and aortic crossclamp time were
      significantly correlated with operative mortality and that obesity was correlated
      with sternal wound infection. Stepwise multiple logistic regression identified
      that old age (> or = 70 years) (p < 0.0001), long perfusion time (p < 0.0001),
      and emergency operation (p = 0.0004) are risk factors for operative mortality and
      that obesity (p = 0.0009) is the only significant risk factor for sternal wound
      infection. We conclude that bilateral internal mammary artery grafting does not
      increase operative mortality in properly selected patients. However, this
      procedure should be carefully chosen in elderly (> or = 70 years) patients and
      for emergency operation. Obese patients have a high risk for sternal infection
      after bilateral internal mammary artery grafting.

PMID- 8283886
TI  - Heart transplantation in patients with previous cardiac operations. Excellent
      clinical results.
AB  - A significant proportion of potential transplant recipients have undergone
      previous cardiac procedures and may be subject to an increased risk because of
      technical and other factors inherent in a reoperation. Between December 1985 and
      June 1991, 155 orthotopic heart transplantations were carried out in 146
      patients. Eighty-five transplantations (54.8%) were carried out as the initial
      cardiac operation (group I); 61 operations (45.2%) were performed in patients who
      had previous nontransplant cardiac operations (group II). Preoperative variables
      including hemodynamic indexes, renal function, and status on the waiting list
      were similar between these groups; however, group II patients tended to be older
      than group I patients (51.9 +/- 10.7 versus 47.7 +/- 11.6 years, respectively; p
      < 0.05) and were more likely to have ischemic heart disease (80.3% versus 34.1%)
      than were those in group I. Significantly longer cardiopulmonary bypass time
      (127.6 +/- 44.7 minutes versus 108.2 +/- 18.8 minutes, p < 0.01) and duration of
      operation (448.1 +/- 120.9 minutes versus 353.2 +/- 85.1 minutes, p < 0.01) was
      found in group II. Operative mortality in group I was 4.7% and in group II was
      6.6% (p > 0.9). Group I actuarial survival at 1 year and 5 years was 87.1% +/-
      3.6% and 72.9% +/- 6.2%, respectively. Group II actuarial survival was 85.3% +/-
      4.5% and 76.0% +/- 6.6%, respectively, for the same time periods. In spite of the
      greater technical challenge implied by previous cardiac operations, no
      significant survival differences occurred between these groups (p > 0.9).
      However, patients undergoing a second cardiac transplantation (n = 9) were
      identified as a high-risk subset with operative mortality of 22.8% and 1-year
      survival of only 33.3% +/- 15.7% (p < 0.0003). Cardiac transplantation in
      patients who have undergone previous nontransplant cardiac operations can be
      carried out without compromising immediate or long-term outcome.

PMID- 8283887
TI  - Working heart model of heterotopic heart-lung transplantation in rats.
AB  - A technique for a working heart model of heterotopic heart-lung transplantation
      is described. The donor aorta and left pulmonary artery are anastomosed to the
      recipient's abdominal aorta in an end-to-side fashion. Arterial blood from the
      recipient's abdominal aorta enters the donor left heart via the donor left lung
      and is ejected into the donor ascending aorta by the transplanted left ventricle.
      With this model, the donor left ventricle performs work comparable to that of the
      native heart without hypoxia. This model is easily reproducible and can be
      applied to various studies, including long-term assessments of cardiac
      remodeling, long-term efficacy of cardiac preservation, and posttransplantation
      ventricular performance under more physiologic conditions.

PMID- 8283888
TI  - Endothelin content of bronchoalveolar lavage fluid from allotransplanted pigs is
      increased during unmodified rejection.
AB  - To find a new method for detection of rejection of allotransplanted lungs, we
      studied the endothelin content of bronchoalveolar lavage fluid by
      radioimmunoassay. Left-sided lung allotransplantation was performed in pigs. One
      group of animals received no treatment with immunosuppressive drugs (rejection
      group), the other group of animals (treated group) was treated with a triple-drug
      immunosuppressive regimen (cyclosporine, azathioprine, and methylprednisone), and
      nontransplanted lungs were controls. The endothelin content in bronchoalveolar
      lavage fluid was significantly elevated in the group of pigs with unmodified
      rejection (29.20 +/- 1.96 pg/ml) compared with that in the immunosuppressed group
      (15.3 +/- 2.4 pg/ml) and control group (4.27 +/- 1.23 pg/ml). The measurements
      were made from 5, 33, and 11 samples of bronchoalveolar lavage fluid from the
      rejection, treated, and control groups, respectively. These results suggest that
      endothelin content of bronchoalveolar lavage fluid could be a marker of lung
      allograft rejection.

PMID- 8283889
TI  - Intraoperative myocardial ischemia detection with laser-induced fluorescence.
AB  - Myocardial ischemia can be detected at the mitochondrial level by measuring
      shifts in nicotinamide adenine dinucleotide and its reduced form. Using a pulsed
      nitrogen laser and an optical multichannel analyzer, we monitored myocardial
      metabolism by measuring laser-induced nicotinamide adenine dinucleotide (reduced
      form) fluorescence in a large animal model of acute ischemia. Eight opened-chest
      sheep underwent occlusion of branches of the left anterior descending coronary
      artery, establishing a 15% infarct of the left ventricle. For the simulation of
      the clinical scenario, after 60 minutes of occlusion, the animals were supported
      by cardiopulmonary bypass, the aorta was crossclamped, and cold crystalloid
      cardioplegic solution was administered. The occlusion was removed after 10
      minutes, and two additional doses of cardioplegic solution were delivered at 10
      minute intervals. The aortic crossclamp was released, and a 30-minute period of
      reperfusion on bypass ensued. The hearts were then weaned off bypass and allowed
      to recover. Laser-induced fluorescence was measured inside, outside, and along
      the border of the infarct. Baseline measurements were made before occlusion,
      immediately after occlusion, and then at 5, 10, and 20 minutes after occlusion.
      The results show that immediately after occlusion there is a 200% +/- 30% (mean
      +/- standard deviation) increase in laser-induced fluorescence in the infarct
      zone, a 110% +/- 30% increase along the border, and no significant change in the
      area outside the infarct. The fluorescence in the infarct reaches a plateau in 5
      minutes at 270% +/- 30%, whereas along the border it reaches a peak near end
      ischemia of 110% +/- 40%. With the first dose of cardioplegic solution,
      fluorescence increases outside the infarct and decreases inside the infarct and
      along the border to 120% +/- 30%, where it remains for all areas until the aortic
      crossclamp is removed. Fluorescence then drops to 70% +/- 20% and finally returns
      to baseline after 5 minutes of recovery. All of these shifts in laser-induced
      fluorescence were statistically significant (p < 0.01). The changes noted with
      doses of cardioplegic solution reflect the hypothermic and hyperkalemic effects
      on the myocardium. Laser-induced fluorescence provides a sensitive and specific
      method of monitoring myocardial ischemia during the operation. It also provides
      instantaneous feedback of metabolic changes that may be useful in evaluating the
      effects of different cardioplegic regimens and in monitoring reperfusion injury.

PMID- 8283890
TI  - Cardiac myocyte functional and biochemical changes after hypothermic preservation
      in vitro. Protective effects of storage solutions.
AB  - In this study, we evaluated cardiac myocyte viability and function under
      hypothermic conditions with four types of storage solutions, saline solution,
      Euro-Collins solution, University of Wisconsin solution, and MCDB 107 medium.
      Cardiac myocytes were isolated from neonatal rat ventricles by collagenase
      dispersion and cultured for 4 days with MCDB 107 medium. A total of 12.5 x 10(5)
      myocytes per culture dish was used and the myocytes were incubated at 4 degrees C
      for 6, 12, 18, and 24 hours in the various storage solutions. After each
      incubation time, creatine kinase and lactate dehydrogenase were measured in the
      storage solutions. The myocytes were then incubated for 24 hours at 37 degrees C
      to evaluate the recovery of the myocyte beating rate. In the MCDB 107 group (n =
      7), the recovery ratio of myocyte beating rate was complete by 12 hours, then
      decreased to 44.8% of control (beating rate before hypothermic incubation) at 24
      hours. The saline, Euro-Collins, and University of Wisconsin groups (n = 7 each)
      had significantly lower recovery ratios than the MCDB 107 group (at 12 hours:
      61.0%, 32.2%, and 48.9%; at 18 hours: 0.0%, 5.5%, and 15.1% of control,
      respectively). Release of creatine kinase and lactate dehydrogenase in the MCDB
      107 group gradually increased and at 24 hours was 143.2 mIU/flask and 486.2
      mIU/flask, respectively. However, the saline and University of Wisconsin groups
      had significantly increased creatine kinase and lactate dehydrogenase values at
      24 hours (creatine kinase: 334.6 and 319.6 mIU/flask; lactate dehydrogenase:
      821.6 and 654.4 mIU/flask, respectively). The Euro-Collins group showed the
      greatest increase in both markers (creatine kinase: 1587.5, lactate
      dehydrogenase: 2106.9 mIU/flask). In summary, saline and University of Wisconsin
      solutions showed a beneficial effect on recovery of myocyte viability at 12 hours
      compared with Euro-Collins solution, however MCDB 107 medium had the best overall
      protective effect on cultured myocytes. Accordingly, alternate hypothermic
      storage solutions, such as cell-culture medium, may have protective
      characteristics that are suitable for cardiac preservation.

PMID- 8283891
TI  - Effects of fatty acids on myocardial calcium control during hypothermic
      perfusion.
AB  - Although hypothermia is regarded as providing protection of the myocardium during
      cardiac operations, rapid cooling of the myocardium in the nonarrested state may
      have detrimental effects on the function of the myocardial cell membrane as a
      permeability barrier. We therefore measured total cellular calcium in isolated
      working rat hearts, receiving either glucose (11.1 mmol/L) or glucose plus
      palmitate (1.2 mmol/L), before, during, and after a 40-minute hypothermic arrest
      (10 degrees C, Langendorff perfusion). In both groups a rise in total cellular
      calcium, measured by 45Ca2+ technique, was observed during hypothermia, followed
      by a decline on rewarming. However, the rise in total cellular calcium during
      hypothermia was significantly (p < 0.05) higher in hearts perfused with palmitate
      (from 1.0 +/- 0.2 to 3.5 +/- 0.2 nmol/mg dry weight) compared with that in
      glucose-perfused hearts (from 1.1 +/- 0.13 to 2.6 +/- 0.2 nmol/mg dry weight).
      Palmitate-perfused, but not glucose-perfused, hearts showed arrhythmias and
      delayed pressure development 1 to 2 minutes after rewarming. In addition cardiac
      output of these hearts was significantly lower (p < 0.025) than that of glucose
      perfused hearts 5 to 10 minutes after rewarming. These data show that hypothermia
      per se causes a net calcium uptake in isolated rat hearts and that this effect is
      aggravated by high concentrations of fatty acids. Thus the impaired recovery of
      myocardial function in palmitate-perfused hearts can possibly be related to a
      distorted calcium handling.

PMID- 8283892
TI  - Effectiveness of coenzyme Q10 on myocardial preservation during hypothermic
      cardioplegic arrest.
AB  - A prospective, randomized, double-blind trial assigned 11 patients to receive
      coenzyme Q10 and 11 to receive none. Patients pretreated with coenzyme Q10 had a
      lower left atrial pressure and a lesser incidence of low cardiac output. They
      also had a wider pulse pressure. The right and left ventricular myocardial
      ultrastructure was better preserved in patients receiving preoperative treatment
      with coenzyme Q10. There was no demonstrable benefit to the atrial myocardium.

PMID- 8283893
TI  - Allopurinol pretreatment improves postoperative recovery and reduces lipid
      peroxidation in patients undergoing coronary artery bypass grafting.
AB  - In this prospective, randomized, double-blind, placebo-controlled study, the
      clinical, biochemical, and hemodynamic effects of xanthine oxidase inhibition in
      patients undergoing coronary artery bypass grafting were assessed. Allopurinol
      pretreatment significantly reduced the use of inotropic support after the
      operation (5 of 25 patients versus 13 of 25 patients, p < 0.01) and increased the
      rate of peripheral warming (11.4 +/- 0.85 hours versus 14.4 +/- 1 hours, p <
      0.02). Twenty patients (9 in the allopurinol group and 11 in the placebo group)
      underwent invasive hemodynamic monitoring and intraoperative coronary sinus
      cannulation. The cardiac indexes of both groups were similar before the operation
      and for the first postoperative hour; thereafter, the cardiac index increased
      significantly in only the active treatment group (F = 3.33 and df = 5.90, p <
      0.004). Products of lipid peroxidation (thiobarbituric acid reactive substances)
      increased significantly in only the placebo group, with increases being evident
      both in the systemic circulation (9.5 +/- 3.2 nmol/gm albumin, p < 0.007, and 24
      +/- 5 nmol/gm albumin, p < 0.001, at 30 seconds and 2 minutes of reperfusion,
      respectively) and the coronary sinus (19.4 +/- 5.8 nmol/gm albumin, p < 0.004,
      and 28 +/- 4 nmol/gm albumin, p < 0.001, at 2 and 5 minutes of reperfusion,
      respectively. No significant difference was evident between the groups with
      respect to cardiac enzyme or vitamin E release. It is proposed that xanthine
      oxidase inhibition exerts its beneficial effects by reducing the level of free
      radical activity associated with reperfusion during coronary artery bypass
      grafting.

PMID- 8283895
TI  - The effect of reperfusion pressure on early outcomes after coronary artery bypass
      grafting. A randomized trial.
AB  - Among 60 patients randomly assigned to a reperfusion pressure of 50 mm Hg or one
      of 75 mm Hg (30 mm Hg during the first 2 minutes in both groups) during initially
      hyperkalemic, controlled aortic root reperfusion after coronary artery bypass
      grafting, no in-hospital deaths occurred, no patient received an intraaortic
      balloon pump, no patient had new Q waves, and creatine kinase MB release was
      similar in the two groups. Median interval between the beginning of reperfusion
      and the return of rhythmic cardiac contractions in the 50 mm Hg group was 7
      minutes; in the 75 mm Hg group, it was 5 minutes (P = 0.1). The initial reactive
      hyperemic response was greater in the 75 mm Hg group. There were no believable
      differences (P < 0.1) between the two groups in postoperative cardiac output,
      left and right atrial pressure, arterial blood pressure, and prevalence of
      catecholamine administration.

PMID- 8283894
TI  - Loss of endothelium-dependent vasodilatation and nitric oxide release after
      myocardial protection with University of Wisconsin solution.
AB  - University of Wisconsin solution has proved to be a superior form of cardioplegia
      for cardiac transplantation, demonstrating better functional recovery than that
      provided by extracellular crystalloid solutions. Furthermore, experimental data
      have suggested a role for University of Wisconsin solution in protection of the
      neonatal heart during operations for congenital heart defects. However,
      significant concerns have been raised regarding potential endothelial injury from
      the high potassium concentration contained in University of Wisconsin solution
      that could affect its safety and thus its clinical application. Fourteen neonatal
      (aged 1 to 3 days) piglet hearts were harvested and supported on an isolated,
      blood-perfused circuit. Endothelium-dependent vasodilatation was measured by
      bradykinin (10(-6) mol/L) infusion and nitric oxide release was determined.
      Endothelium-independent vasodilatation was then induced by sodium nitroprusside
      (10(-6) mol/L) infusion. A 2-hour period of cold cardioplegic arrest was
      instituted with multidose University of Wisconsin solution (group 1, n = 7) or
      blood cardioplegia (group 2, n = 7). After reperfusion and stabilization, another
      stimulation with bradykinin and nitroprusside was carried out and nitric oxide
      was again measured. After 2 hours of arrest with University of Wisconsin
      solution, there was a near-complete loss of vasodilatation in response to
      bradykinin infusion; coronary blood flow reached 245% of baseline before arrest
      versus only 117% of baseline after arrest (p = 0.0011). This correlated with an
      inability of the endothelium to release nitric oxide (96 +/- 30 nmol/min before
      arrest versus -32 +/- 9 nmol/min after arrest, p = 0.0039. In group 2, the
      vasodilatory response to bradykinin was preserved after arrest and reperfusion;
      265% of baseline before arrest versus 222% of baseline after arrest. These
      results demonstrate a loss of endothelium-dependent vasodilatation after
      multidose University of Wisconsin cardioplegia caused by the inability of the
      endothelium to release nitric oxide. In contrast, blood cardioplegia does not
      result in impaired endothelial function.

PMID- 8283896
TI  - Prospective evaluation and clinical utility of on-site monitoring of coagulation
      in patients undergoing cardiac operation.
AB  - Although laboratory coagulation tests permit a rational approach to both
      diagnosis and management of coagulation disorders after cardiopulmonary bypass,
      their clinical utility is limited by delays in obtaining results. This study was
      designed to evaluate prospectively the impact of on-site coagulation testing on
      blood product use, operative time, and intraoperative management of microvascular
      bleeding. Patients who underwent cardiac procedures involving cardiopulmonary
      bypass and subsequently developed microvascular bleeding were randomly assigned
      to receive either standard therapy (n = 36) or therapy defined by a treatment
      algorithm based on results from an on-site coagulation monitoring laboratory (n =
      30). No differences were found between treatment groups in hematologic assay
      data, operative procedures, or duration of cardiopulmonary bypass. Patients
      treated in accordance with on-site laboratory results (algorithm therapy)
      received significantly less intraoperative fresh frozen plasma (0.4 +/- 1.1 U
      versus 2.4 +/- 2.8 U; p = 0.0006) during the treatment interval, had shorter
      operative times, and had less mediastinal chest tube drainage during the initial
      perioperative interval (158 +/- 169 ml versus 326 +/- 258 ml; p = 0.003) than did
      patients in the standard therapy group. Patients who underwent algorithm therapy
      also received fewer platelet (1.6 +/- 5.9 versus 6.4 +/- 8.2 U; p = 0.02) and red
      blood cell (1.9 +/- 1.7 U versus 4.1 +/- 4.1 U; p = 0.01) transfusions after the
      operation. Nine of 36 (25%) standard group patients received initial therapy
      which differed from that which would have been guided by the on-site algorithm
      protocol. Our findings indicate that rapid and accurate coagulation test results
      can guide specific therapy and optimize treatment of microvascular bleeding in
      patients who undergo cardiac operations.

PMID- 8283897
TI  - Platelet-leukocyte activation and modulation of adhesion receptors in pediatric
      patients with congenital heart disease undergoing cardiopulmonary bypass.
AB  - Cardiopulmonary bypass has been shown in adults to activate platelets and
      leukocytes, lead to the formation of circulating platelet-leukocyte conjugates,
      and alter adhesive receptors on both cell types. Pediatric patients with
      congenital heart disease undergoing cardiopulmonary bypass, however, have not
      been extensively studied and may represent a group at particular clinical risk
      for bleeding and pulmonary dysfunction. We studied 13 patients with congenital
      heart disease undergoing operations necessitating bypass, 7 with cyanotic and 6
      with noncyanotic congenital heart disease. We determined that (1) the surface
      density of platelet glycoprotein Ib was significantly lower at baseline and
      throughout bypass in patients with cyanotic heart disease than in noncyanotic
      patients; (2) platelet glycoprotein Ib in both cyanotic and noncyanotic
      congenital heart disease decreased significantly during bypass, with a nadir of
      75% of baseline values; (3) platelets were activated to a high degree, comparable
      with that seen in adults; (4) mean circulating monocyte-platelet conjugates rose
      significantly during bypass, increasing from 36% to 66% by the end of bypass,
      whereas neutrophil-platelet conjugates and lymphocyte-platelet conjugates
      declined; and (5) both monocytes and neutrophils were activated by
      cardiopulmonary bypass, as assessed by increased surface expression of CD11b and,
      in the case of monocytes, CD11b expression continued to increase even after
      termination of bypass. Patients with cyanotic and noncyanotic heart disease did
      not differ with respect to platelet or leukocyte activation or the formation of
      platelet-leukocyte conjugates. We conclude that in children with congenital heart
      disease cardiopulmonary bypass causes loss of platelet adhesion receptors,
      activation of platelets, formation of platelet-leukocyte conjugates, and
      leukocyte activation. Cyanotic and noncyanotic patients are qualitatively
      similarly affected; however, cyanotic patients demonstrate a baseline deficit in
      the platelet adhesion receptor glycoprotein Ib. These cellular changes may
      contribute to both the hemostatic and inflammatory complications associated with
      cardiopulmonary bypass.

PMID- 8283898
TI  - Heparin coating of an extracorporeal circuit partly improves hemostasis after
      cardiopulmonary bypass.
AB  - Heparin coating of an extracorporeal circuit for cardiopulmonary bypass improves
      the hemocompatibility of the circuit and reduces the inflammatory response of the
      body. It has not been established, however, that heparin coating also improves
      postoperative hemostasis. We therefore performed a study in 30 patients who
      underwent a routine coronary artery bypass graft operation subjected to
      cardiopulmonary bypass with an uncoated (control) or a heparin-coated
      extracorporeal circuit (Duraflo II). We found significantly higher plasma levels
      of heparin in the Duraflo II group. However, we found no significant differences
      between the two groups with regard to other parameters of activation of the
      fibrinolytic and coagulation systems and to activation of platelets.
      Postoperative blood loss and donor blood transfusions were reduced in the Duraflo
      II group but not to a statistically significant extent. We conclude that heparin
      coating of an extracorporeal circuit improves anticoagulation but does not
      significantly reduce platelet activation, fibrinolysis, postoperative blood loss,
      and donor blood transfusions in routine coronary bypass operations.

PMID- 8283899
TI  - A new variation of tracheobronchoplastic operation.
AB  - A new variation of tracheobronchoplastic operations that we named modified
      plastic surgery was applied successfully on six patients with lung cancer and one
      with carcinoid adenoma. Modified plastic surgery consists of adaptive shaping of
      healthy portions of the bronchi and elimination of parts affected by the
      pathologic process, which usually required the respective lung resection.
      Suturing of the fragments reestablished the airways and rendered the formation of
      postoperative stenoses and anastomoses practically impossible. Indications for
      this type of operation were decided individually according to the location of the
      process and the requirements for complete resection in the cases with lung
      cancer. In many instances this type of operation was the only option for
      preservation of the organ.

PMID- 8283900
TI  - A potential mechanism of vasodilation after warm heart surgery. The temperature
      dependent release of cytokines.
AB  - Peripheral vasodilation is a common feature of warm heart surgery and creates
      clinical concerns when pressor agents become necessary because of the potential
      for some of these drugs to adversely affect flow through newly engrafted arterial
      and venous bypass conduits. The possible role of a temperature-dependent
      production of cytokines in the pathogenesis of this vasodilation was investigated
      in a two-part study. In part I, lipopolysaccharide-activated peritoneal rabbit
      macrophages (5 x 10(6)/ml) were incubated at 30 degrees or 37 degrees C up to 9
      hours and the concentration of tumor necrosis factor released in the supernatant
      was serially measured by a bioassay. Tumor necrosis factor production was found
      to increase over time for each of the two temperatures of incubation but was
      significantly higher throughout the observation period in normothermic
      experiments than in those done at 30 degrees C. Part II was a prospective
      clinical study involving 30 patients who underwent either cold (core temperature
      28 degrees to 30 degrees C, n = 15) or warm (37 degrees C, n = 15)
      cardiopulmonary bypass and in whom serum levels of tumor necrosis factor alpha,
      interleukin-1 beta, and interleukin-6 were measured by enzyme-linked
      immunosorbent assays at 2, 4, 10, and 24 hours after bypass. Cytokine levels were
      found to be consistently higher in patients having normothermic bypass.
      Differences between the two groups were significant 2 hours after bypass for
      tumor necrosis factor alpha and interleukin-6 (p < 0.02 and p = 0.0001,
      respectively) and 4 and 10 hours after bypass for interleukin-1 beta (p < 0.01
      and p < 0.04, respectively). The incidence of vasodilation necessitating
      vasopressor support was twofold higher in the normothermic group (six patients
      versus three in the hypothermic group). Taken as a whole, patients supported by
      pressor agents had significantly higher cytokine levels after bypass than those
      who did not require pressor therapy. Our results suggest that vasodilation
      occurring with warm heart operation is, at least partly, mediated by a
      temperature-dependent release of cytokines. Vasodilation might therefore be
      mitigated by simply allowing the core temperature to drift during bypass. Our
      recent clinical experience suggests that this "tepid" heart surgery (32 degrees
      to 34 degrees C) effectively blunts most of the vasodilatory response to strictly
      normothermic bypass without compromising maintenance of myocardial aerobiosis
      during arrest.

PMID- 8283902
TI  - The role of mediastinoscopic biopsy in preoperative assessment of lung cancer.

PMID- 8283901
TI  - Determination of optimum retrograde cerebral perfusion conditions.
AB  - Retrograde cerebral perfusion through a superior vena caval cannula is a new
      technique used to protect the brain during operations on the aortic arch. We
      measured cerebral tissue blood flow, oxygen consumption, and cerebrospinal fluid
      pressure under various perfusion conditions in hypothermic (20 degrees C) mongrel
      dogs (n = 18, 12.8 +/- 0.6 kg) to determine the optimum conditions for retrograde
      cerebral perfusion. Retrograde cerebral perfusion was performed by infusion via
      the superior vena caval cannula and drainage via the ascending aortic cannula
      while the inferior vena cava and azygos vein were clamped. Retrograde cerebral
      perfusion was performed as the external jugular venous pressure was changed from
      15 to 35 mm Hg in increments of 5 mm Hg. Cerebral tissue blood flow was measured
      by the hydrogen clearance method. Hypothermic retrograde cerebral perfusion with
      an external jugular venous pressure of 25 mm Hg provided about half the cerebral
      tissue blood flow of hypothermic (20 degrees C) cardiopulmonary bypass with a
      flow rate of 1000 ml/min (13.7 +/- 7.9 versus 32.7 +/- 8.5 ml/min per 100 gm). It
      decreased significantly as the external jugular venous pressure was decreased
      from 25 to 15 mm Hg but did not increase significantly as the external jugular
      venous pressure was increased from 25 to 35 mm Hg. Whole-body oxygen consumption
      during hypothermic retrograde cerebral perfusion with an external jugular venous
      pressure of 25 mm Hg was one quarter of that during hypothermic cardiopulmonary
      bypass (3.4 +/- 0.7 versus 12.7 +/- 5.6 ml/min) and varied in proportion to
      external jugular venous pressure. The cerebrospinal fluid pressure was a little
      lower than the external jugular venous pressure (19.2 +/- 4.5 mm Hg versus 24.8
      +/- 2.4 mm Hg) but also varied with the external jugular venous pressure. The
      cerebrospinal fluid pressure remained lower than 25 mm Hg so long as the external
      jugular venous pressure remained lower than 25 mm Hg. High external jugular
      venous pressure was associated with high intracranial pressure, which restricts
      cerebral tissue blood flow and may cause brain edema. We believe that a venous
      pressure of 25 mm Hg is the optimum condition for retrograde cerebral perfusion.

PMID- 8283903
TI  - Extragonadal malignant germ cell tumor of the lung.

PMID- 8283904
TI  - Thoracoscopic surgery for pneumothorax.

PMID- 8283905
TI  - Thoracoscopic resection of a pericardial cyst: a case report.

PMID- 8283906
TI  - Repair of acute type A aortic dissection after cesarean section in the thirty
      ninth week of pregnancy.

PMID- 8283907
TI  - Correction of a kink in tubular prosthesis in chronic dissection of the
      descending thoracic aorta.

PMID- 8283908
TI  - Ligation of the thoracic duct through transabdominal phrenotomy for chylothorax
      after heart operations.

PMID- 8283909
TI  - Heart operation in a patient with refractory idiopathic thrombocytopenic purpura.

PMID- 8283910
TI  - Disappearance of periodic breathing after heart operations.

PMID- 8283911
TI  - Concentric wear of the Delrin disc of a Bjork-Shiley prosthesis: an uncommon
      cause of prosthetic incompetence.

PMID- 8283912
TI  - Assessment of number of cusps in aortic lesions by Doppler imaging: surgical
      correlations.

PMID- 8283913
TI  - A new surgical approach to apical segment lung diseases, including carcinomas and
      inflammatory diseases.
AB  - A new surgical approach to lung cancer and inflammatory pulmonary diseases has
      been developed. This approach focuses on diseases located in the apical segments
      of the lung and showing invasion or severe adhesion to the apical thoracic wall
      or to vital organs near the thoracic dome (including superior sulcus tumors). The
      conventional posterolateral approach leaves the surgeon "blind" because it forces
      the surgeon to perform the operation looking up through a tube from the bottom.
      This limited view makes accurate assessment of the surrounding vital organs
      involved in these diseases almost impossible and also increases the risk of
      injury to adjacent vital organs. The incision in this new approach allows
      extensive retraction of the scapula to provide easier access to the posterior
      chest wall. Because the incision curves upward anteriorly, rather than downward
      as usual, it gives excellent exposure of the apical anterior thoracic region. In
      the few cases in which we have used this approach, we have found that the
      surgical field is in plain view and that the operation is consequently safer and
      easier. So far we have not encountered any complications, and we can recommend
      this approach with confidence.

PMID- 8283914
TI  - Preliminary results with a new technique for repairing elongated chordae
      tendineae of the anterior mitral valve leaflet.

PMID- 8283915
TI  - Extent and distribution of the perfusion areas of the coronary artery selected
      for bypass grafting: assessment by intraoperative myocardial contrast
      echocardiography.

PMID- 8283916
TI  - Repair of pectus deformities with sternal support.
AB  - During the past 25 years, 252 children underwent repair of pectus deformities.
      There were 195 male and 57 female patients, of whom 227 had pectus excavatum and
      25 had pectus carinatum. Of the 252 patients, 113 underwent repair at between 2
      and 5 years of age. Exercise limitation was reported by 51%, and 32% had frequent
      respiratory infections or asthma. Repair was performed through a transverse
      incision with subperiosteal resection of the lower four or five costal
      cartilages, from sternum to costochondral junction bilaterally. A transverse
      wedge osteotomy was made through the anterior table of the sternum, with fracture
      but no displacement of the posterior table. For children younger than 5 years (n
      = 108), the periosteal sheath of the fifth rib from each side was sewn together
      behind the sternal tip. For older patients (n = 136), a thin steel strut was used
      for sternal support for 6 months. There were no deaths within the first year.
      Complications included seroma (16), atelectasis (12), pneumothorax (three), and
      recurrent chest depression (three). More than 98% of patients had improvements in
      exercise tolerance, endurance, respiratory symptoms, and cosmetic appearance;
      these improvements were considered excellent results. Operation at an early age
      with routine use of substernal support with minimal preoperative and
      postoperative testing has provided excellent results at a low cost.

PMID- 8283917
TI  - Tumor necrosis factor induces doxorubicin resistance to lung cancer cells in
      vitro.
AB  - Tumor necrosis factor can alter the cell cycle of tumor cells and protect
      hematopoietic stem cells from cell cycle-specific chemotherapy, but the ability
      of tumor necrosis factor to protect cancer cells from chemotherapy by
      manipulation of the cell cycle is unknown. Twenty-four-hour exposure of A549
      human lung cancer cells to tumor necrosis factor shifted cells from S phase to
      G0/G1 phase as determined by analysis of isolated cell nuclei with an FACScan
      Cell Sorter. This effect was not seen in cells exposed to interleukin-1 or
      interleukin-6. Growth assays demonstrated that tumor necrosis factor slowed the
      doubling time of A549 cells, confirming that tumor necrosis factor caused G0/G1
      arrest in these cells. Pretreatment with tumor necrosis factor rendered cells
      resistant to subsequent 1-hour exposure to doxorubicin, a chemotherapeutic agent
      active against S phase cells. Tumor necrosis factor did not protect cells against
      either cisplatin or mitomycin C, drugs not specific for S phase. Measurement of
      intracellular drug levels indicated that pretreatment with tumor necrosis factor
      did not affect doxorubicin uptake or efflux. These findings suggest that cells
      producing tumor necrosis factor within a tumor may render surrounding malignant
      cells resistant to cell cycle-specific chemotherapy, and this mechanism may
      explain failure of sequential immunotherapy-chemotherapy protocols.

PMID- 8283918
TI  - Isolated single lung perfusion with doxorubicin is effective in eradicating soft
      tissue sarcoma lung metastases in a rat model.
AB  - The only effective therapy for patients with metastatic soft tissue sarcoma in
      the lung is surgical resection, with a 5-year survival of approximately 25%.
      Because systemic chemotherapy has not significantly affected survival in these
      patients, we began to investigate locoregional chemotherapy. We have previously
      shown that isolated single lung perfusion with doxorubicin in the rat results in
      higher lung tissue levels and lower systemic toxicity than does high-dose
      intravenous therapy. In the present study, we examined the safety of isolated
      lung perfusion with doxorubicin and its efficacy in the treatment of experimental
      pulmonary metastases from soft tissue sarcoma. In experiment 1, 15 F344 rats were
      randomized into three groups (n = 5): group I had isolated left lung perfusion
      with doxorubicin 320 micrograms/ml in saline solution; group II had left isolated
      lung perfusion with doxorubicin 480 micrograms/ml and group III with doxorubicin
      640 micrograms/ml. All perfusions with doxorubicin were at 0.5 ml/min for 10
      minutes followed by perfusion of saline solution for 5 minutes. On day 21, all
      animals underwent right (contralateral) pneumonectomy and were observed for over
      10 days. In experiment 2, two groups of F344 rats were injected intravenously
      with 10(7) viable methylcholanthrene-induced sarcoma cells on day 0. On day 7,
      group I (n = 12) had left isolated lung perfusion with saline solution only and
      group II (n = 15) had isolated lung perfusion with doxorubicin 320 micrograms/ml.
      On day 21, all animals were killed, and their lungs were stained for metastases.
      Routine histologic sections from three animals from group II were examined. In
      experiment 1, 80% of the animals in group I survived contralateral pneumonectomy.
      There were no survivors in groups II and III. In experiment 2, three animals died
      after isolated lung perfusion (one from group I and two from group II), and one
      animal (group I) was excluded because of mediastinal tumor. All animals in both
      groups had massive tumor replacement of the right (untreated) lung. Group I
      animals had massive tumor replacement of the left (treated) lung, whereas animals
      in group II had eradication of metastases in nine of ten cases; no microscopic
      evidence of tumor was detected in all three animals evaluated for microscopic
      disease. Isolated lung perfusion with doxorubicin 320 micrograms/ml is safe and
      effective in eradicating experimental pulmonary sarcoma metastases in this model.

PMID- 8283919
TI  - Descending necrotizing mediastinitis. Advantage of mediastinal drainage with
      thoracotomy.
AB  - Descending necrotizing mediastinitis can occur as a complication of oropharyngeal
      and cervical infections that spread to the mediastinum via the cervical spaces.
      Delayed diagnosis and inadequate mediastinal drainage through a cervical or minor
      thoracic approach are the primary causes of a high published mortality rate (near
      40%). Between 1985 and 1992, six men (mean age, 49 years) with descending
      necrotizing mediastinitis were surgically treated at our institution. The primary
      oropharyngeal infection was peritonsillar abscess (three cases) and odontogenic
      abscess (three cases). In all cases, occurrence of respiratory insufficiency
      associated with serious cervical infection suggested the mediastinitis diagnosis.
      Computed tomographic scans confirmed the mediastinitis, showing mediastinal
      abscess and mediastinal emphysema. All patients underwent surgical drainage of
      the deep neck infection combined with mediastinal drainage through a thoracic
      approach. The outcome was favorable in five patients who had mediastinal drainage
      through a thoracotomy; the patient who had mediastinal drainage through a minor
      thoracic approach (anterior mediastinotomy) died of tracheal fistula on
      postoperative day 18. In our experience, aggressive mediastinal drainage by a
      thoracotomy approach regardless of the level of mediastinal involvement led to
      improvement in survival of these patients, with a 17% mortality rate.

PMID- 8283920
TI  - Squamous cell carcinoma of the esophagus with mucin-secreting component.
      Mucoepidermoid carcinoma.
AB  - Among 1058 patients with cancer of the esophagus, 20 patients with mucoepidermoid
      or adenosquamous cell carcinoma of the esophagus and cardia, together defined as
      squamous cell carcinoma with a mucin-secreting component, were seen over a 10
      year period. Their records were reviewed and appropriate comparisons were also
      made with the more common squamous cell carcinomas and adenocarcinomas. Squamous
      cell carcinoma with mucin-secreting component comprised 1.9% of all tumors
      encountered. Clinical features including age, male predominance, symptoms at
      presentation, length of tumor, and appearance of tumor did not differ from those
      of squamous cell and adenocarcinoma. The location of these tumors, however,
      followed that of squamous cell carcinomas, with 55% in the middle third and 25%
      in the lower third. Adenocarcinomas were found predominantly at the cardia (83%).
      Operability and resectability rates were higher than those of squamous cell and
      adenocarcinomas. Primary treatment consisted of resection in 19 of the 20
      patients (95%); 18 of them had a one-stage resection and 1 patient had a two
      stage resection. Postresection staging showed that 5% had stage I disease, 16%
      had stage II, and 79% had stage III disease. None of the patients who underwent
      resection died within 30 days of the operation. The mortality after 30 days was
      10.5%. The 1 patient in whom intubation was the primary treatment had distant
      metastases at the time of presentation (stage IV). The overall median survival
      was 9.2 months. The median survival for patients who had their tumors resected
      was 9.5 months. The survival improved to 33 months for curative resection but was
      only 8.7 months for palliative resection. The 1-, 2-, and 5-year survivals were
      46%, 39%, and 0%, respectively. This prognosis was not significantly different
      from that of patients with squamous cell carcinoma or adenocarcinoma.

PMID- 8283921
TI  - Decreased mesenteric blood flow supplying retrosternal esophageal ileocoloplastic
      grafts during positive-pressure breathing.
AB  - Esophageal replacement after esophagogastric injury caused by ingestion of lye
      may require the interposition of a retrosternal ileocolic graft. In this new
      anatomic situation, the mesenteric circulation supplying the graft is subjected
      to the intrathoracic pressure surrounding the graft. Thus, mesenteric blood flow
      supplying the graft may be impaired when intrathoracic pressure is increased
      during mechanical ventilation. This study was designed to evaluate the effect of
      increasing intrathoracic pressure by application of a positive end-expiratory
      pressure on mesenteric blood flow supplying esophageal ileocolic grafts. Eight
      cases were studied in the immediate postoperative period. Miniaturized
      implantable Doppler microprobes were sutured to the single artery supplying the
      graft and connected to an 8 MHz pulsed Doppler flowmeter. Two sets of
      measurements were successively performed with zero end-expiratory pressure
      ventilation and after application of a 15 cm water positive end-expiratory
      pressure. Positive end-expiratory pressure induces mean arterial pressure (-12%);
      p < 0.05) and cardiac output (-17%; p < 0.05) decrease. Mesenteric blood flow
      also decreases (-38%; p < 0.05) as did the mesenteric blood flow/cardiac output
      ratio, suggesting a potential mesenteric vasoconstriction assessed by mesenteric
      vascular resistance increase and mesenteric diastolic blood flow velocity
      decrease. These results suggest that, in the particular anatomic situation of the
      graft, increased intrathoracic pressure induces mesenteric blood flow decrease in
      relation to systemic hemodynamic alterations associated with perivisceral
      pressure increase. This change may be deleterious to graft perfusion.

PMID- 8283922
TI  - Surgical treatment of aortic coarctation in infants younger than three months:
      1985 to 1990. Success of extended end-to-end arch aortoplasty.
AB  - There remains controversy regarding the appropriate surgical treatment of
      coarctation of the aorta in infants. In 1985 we introduced the extended end-to
      end repair into our practice and now wish to present a review of our recent
      experience. One hundred fifty-one infants younger than 3 months of age underwent
      repair of coarctation between 1985 and 1990. In 25% and 33% of the patients,
      there was hypoplasia of the isthmus and of the transverse arch, respectively.
      Surgical procedures were as follows: subclavian flap angioplasty in 15 patients,
      resection with a traditional end-to-end anastomosis in 43, and resection with an
      extended end-to-end anastomosis into the arch in 77. In 30 patients, the
      extension was proximal to the origin of the left carotid artery (radically
      extended end-to-end anastomosis). Other procedures were used in 16 patients.
      Mortality (13 early and 12 late deaths) was related on multivariate analysis to
      the presence of an associated major heart defect, preoperative resuscitation, and
      direct postoperative gradient over the arch. This immediate postoperative
      gradient was significantly lower after both extended and radically extended end
      to-end anastomosis if there was a hypoplastic isthmus, and after radically
      extended end-to-end anastomosis if the transverse arch was hypoplastic. Actuarial
      freedom from recoarctation at 4 years was 57% (confidence limits 28% to 78%)
      after subclavian flap angioplasty, 77% (confidence limits 60% to 87%) after end
      to-end anastomosis, 83% (confidence limits 66% to 92%) after extended end-to-end
      anastomosis and 96% (confidence limits 77% to 100%) after radically extended end
      to-end anastomosis. We conclude that the extended end-to-end anastomosis and
      radical end-to-end anastomosis appear to offer the best prognosis for all infants
      with coarctation. The technique can be applied successfully to almost all types
      of arch anomalies.

PMID- 8283923
TI  - Local recurrence after complete resection for non-small-cell carcinoma of the
      lung. Significance of local control by radiation treatment.
AB  - Of 471 patients undergoing a complete resection for non-small-cell carcinoma of
      the lung between 1972 and 1989, 40 patients (8.5%) had local recurrences without
      extrathoracic distant metastasis. Excluding 8 patients who had malignant pleural
      effusion, we selected 32 patients (24 with hilar-mediastinal lymph node, 6 with
      bronchial stump, and 2 with chest wall recurrence) from the 40 patients and
      assessed the significance of local control by radiotherapy. The median length of
      survival after disease recurrence for these 32 patients was 19 months. Of 29
      patients given radiation treatment, 16 who responded to the treatment survived
      significantly longer than nonresponders (median survival time 27 months versus 6
      months, p < 0.01). Univariate analyses of survival after recurrences in relation
      to various factors revealed that sex and disease-free intervals were significant
      prognostic factors (p < 0.05) other than the effect of radiotherapy. A
      multivariate analysis showed that the effect of radiotherapy was the predominant
      prognostic factor. From these results, we conclude that local control with
      radiation is beneficial in patients with solely locally recurrent tumors in terms
      of improved survival.

PMID- 8283924
TI  - More than thirty-five years of coarctation repair. An unexpected high relapse
      rate.
AB  - Between 1953 and 1985, 109 consecutive patients (17% with isolated coarctation)
      younger than 3 years of age underwent resection of aortic coarctation. These
      patients had nonelective operations because of congestive heart failure or severe
      systemic hypertension not responding to medical therapy. Special surgical
      techniques were used to lower the prevalence of restenosis. Hospital mortality
      was 32% (35 patients). Logistic regression analysis proved that age at operation,
      pulmonary artery banding, and type of repair were independent predictors of
      hospital death. Late mortality occurred in 9 patients. Associated cardiac
      anomalies were an independent prognostic factor for late mortality. The operation
      rate for recoarctation was low (5.8%). However, the follow-up study revealed that
      30 patients (41%) had recoarctation. The Kaplan-Meier estimate of recoarctation
      is 86% after 30 years' follow-up in patients undergoing classic end-to-end
      anastomosis with silk sutures (n = 48). None in the group with an "extended"
      anastomosis and polypropylene sutures (n = 26) had recoarctation. The Cox
      analysis revealed age at operation under 6 months to be prognostic for
      recoarctation. Because of the shorter period of follow-up, the extended
      anastomosis with polypropylene sutures proved not to be a significant prognostic
      factor for recoarctation. In the late postoperative period (mean follow-up 16.7
      years), blood pressure was elevated in 49% of the patients. At last follow-up 27
      (36%) of the 74 survivors had aortic valve disease. Patients operated on for
      coarctation of the aorta under the age of 3 years need lifelong follow-up for
      detection of restenosis, hypertension, and valvular disease. Reoperation-free
      rate is not a good criterion to judge the outcome of operation for coarctation.
      Longer follow-up will be needed to investigate whether or not the use of the
      extended anastomosis technique with polypropylene sutures lowers the prevalence
      of recoarctation.

PMID- 8283925
TI  - Surgical treatment of multiple ventricular septal defects using a biologic glue.
AB  - The closure of multiple ventricular septal defects remains a surgical challenge.
      Mortality and morbidity are high. Left ventricular incision and multiple patches
      or stitches impair septal motion and function. We searched for a method that
      would cause minimal left ventricular and septal dysfunction. The use of fibrin
      seal for closing ventricular septal defects was considered. The method was first
      tested in animals so as to assess the internal resistance of the fibrin seal to
      stretching and fragmentation in addition to its adhesiveness and hence the
      absence of left-to-right embolization of the fibrin seal clot and the long-term
      success of the ventricular septal defect closure further to complete resorption
      of the ventricular septal defect clot. This experimental work was very
      satisfactory. Between April 1986 and September 1991, 15 children were operated on
      with the use of this technique. The overall hospital mortality rate was 6%. There
      were no reoperations for residual ventricular septal defects. All the long-term
      survivors (n = 13) were in excellent clinical condition with no or trivial
      residual shunt attested by color flow mapping investigation. This experimental
      and clinical experience suggests that satisfactory results can be achieved with
      the use of fibrin seal for the closure of multiple muscular ventricular septal
      defects.

PMID- 8283926
TI  - Lipoprotein metabolism and its relationship to atherosclerosis.
AB  - Lipoproteins are macromolecular complexes that transport cholesterol and
      triglycerides through the blood stream. The assembly and secretion of
      lipoproteins occurs in the liver and small intestine, but many modifications and
      transformations occur in the plasma. Plasma levels of cholesterol and
      triglycerides are regulated by both environmental effects on lipid metabolism and
      by genetic factors affecting both apoproteins on the surface of the lipoproteins
      and enzymes in plasma. Abnormalities of the lipoprotein transport system can
      increase an individual's risk for developing atherosclerosis.

PMID- 8283927
TI  - Secondary causes of hyperlipidemia.
AB  - Secondary causes of hyperlipidemia are important to recognize. In fact,
      hyperlipidemia may be a clue to the presence of an underlying systemic disorder.
      It may greatly heighten the risk of atherosclerosis with a raised LDL-c,
      triglyceride-rich lipoprotein excess, and increased lipoprotein(a) as well as
      lowered HDL-c. The search for secondary causes may provide a clue as to why
      patients with primary lipid disorders suddenly develop worsening lipid profiles.
      The point is a crucial one because some acquired causes of hyperlipidemia, such
      as alcohol, estrogens, steroids, or pregnancy, when superimposed on a primary
      familial form of hypertriglyceridemia can result in a saturated removal system
      and a buildup of chylomicrons, which can lead to life-threatening pancreatitis. A
      convenient way to remember secondary causes is to think of the four D's of diet,
      drugs, disorders of metabolism, and diseases. Although diets rich in saturated
      fats and cholesterol are a common cause of the mild hypercholesterolemia seen in
      our society, alcohol excess and weight gain can explain much of the tendency
      toward hypertriglyceridemia. Interestingly anorexia nervosa has long been
      associated with severe but reversible hypercholesterolemia. Several classes of
      drugs need to be considered as common causes of altered lipid profiles.
      Glucocorticoids and estrogens elevate triglycerides and raise levels of HDL-c.
      Anabolic steroids taken orally markedly reduce levels of HDL-c in contrast to
      injectable testosterone, which does not adversely affect the LDL-to-HDL ratio.
      Oral contraceptives affect atherosclerotic risk depending on the kind and doses
      of progestin/estrogen. In those with an underlying primary hypertriglyceridemia
      and associated obesity, estrogenic medications can depress triglyceride removal
      mechanisms, leading to the chylomicronemia syndrome and pancreatitis.
      Antihypertensives have variable effects on lipids and lipoproteins. Although
      short-term thiazide usage raises cholesterol, triglycerides, and LDL-c, long-term
      usage is not necessarily associated with significant alterations in lipid levels.
      Alpha blockers may cause an increase in HDL-c, whereas beta blockers raise
      triglycerides and lower HDL-c. Sympatholytics, angiotensin converting enzyme
      inhibitors, and calcium channel blockers are essentially lipid neutral. Retinoids
      can be associated with increased LDL-to-HDL ratios and occasionally striking
      elevations in triglycerides. Cyclosporine raises LDL-c and lipoprotein(a).
      Classes of drugs that may raise HDL-c include cimetidine, antiepileptic drugs,
      and tamoxifen, but the effect may be seen primarily in women. Hypothyroidism is
      the most common secondary cause of hyperlipidemia after dietary causes are
      considered. A thyroxine and TSH level should be obtained on all new cases of
      clinically important hyperlipidemia.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8283928
TI  - Lipoprotein disorders in diabetes mellitus.
AB  - In IDDM or NIDDM, the total plasma cholesterol and triglycerides are usually
      within normal limits when the blood glucose is controlled. Marked
      hypertriglyceridemia can develop with loss of glycemic control and is often due
      to superimposed genetic abnormalities in lipoprotein metabolism. Tight control in
      IDDM usually reduces LDL and VLDL to normal levels and may raise HDL above the
      normal range. Low HDL cholesterol and mild to moderate elevations of VLDL
      triglyceride are common in NIDDM if obesity or proteinuria is also present. Both
      HDL and LDL may be smaller and more dense and may be enriched with triglyceride
      as compared with cholesterol. These abnormalities may require weight loss for
      control. The increased incidence of cardiovascular disease in diabetes is
      unexplained but is amplified by the well-defined cardiovascular risk factors. The
      new American Diabetes Association guidelines call for treatment of high
      triglycerides and LDL cholesterol to be aggressively reduced. Triglycerides
      should be under 200 mg/dL, are considered borderline high between 200 and 400
      mg/dL, and high when above 400 mg/dL. Low HDL is defined as less than 35 mg/dL.
      Control of obesity with diet and exercise and reduced intake of saturated fat and
      cholesterol are important first steps. If needed, drug therapy is appropriate to
      reduce LDL to levels below 130 mg/dL in all adult diabetics and below 100 mg/dL
      in those with cardiovascular disease.

PMID- 8283929
TI  - Dyslipoproteinemia in women and the elderly.
AB  - Major risk factors predict coronary risk in both women and men. It is inadvisable
      and unwarranted to suggest that women be excluded from cholesterol screening. In
      fact, what evidence is available suggests that women, similar to men, benefit
      from cholesterol lowering. This is not an insignificant issue. Women, similar to
      men, die mostly of coronary atherosclerosis, although atherosclerotic death in
      women occurs 5 to 10 years later than in men. There are some risk factors that
      are unique in women. LDL-c levels may be less predictive of risk in women than in
      men; HDL-c levels may be more predictive. Triglycerides are a stronger predictor
      of risk in women than in men. Finally, diabetes is a major risk factor in women
      and almost eliminates the differences in risk seen in comparing nondiabetic men
      and women. Exogenous gonadal hormones, both in the form of OCs and HRT, have the
      potential to influence coronary risk in women. In premenopausal women, use of OCs
      is associated with increased risk of coronary disease in women who smoke,
      particularly in women older than age 35. In postmenopausal women, estrogen use is
      generally associated with protection against coronary disease. These results may
      be in part due to favorable effects on circulating lipoproteins but may as well
      be related to the protective effects of estrogen on the arterial wall. Definitive
      recommendations about the use of estrogen in postmenopausal women for the primary
      prevention of coronary disease await the completion of clinical trials of
      estrogen alone and in combination with progestins. Cholesterol and its
      lipoprotein subfractions continue to be predictors of both morbidity and
      mortality in older populations. The value of cholesterol-altering therapy in
      older individuals is not as well established in clinical trials as in middle-aged
      men. Nevertheless, there is good reason to believe that the results from both
      primary and secondary prevention studies in younger individuals can readily be
      extrapolated to older individuals. In particular, individuals with symptomatic
      coronary disease but a relatively good prognosis should be offered the same
      benefits from secondary prevention as younger individuals. Thus, although data
      are more limited in women and the elderly than in middle-aged men, there is good
      reason to believe that cholesterol interventions are likely to be effective,
      particularly in postmenopausal women and in older individuals with established
      coronary disease. To withhold therapy based simply on gender or chronologic age
      is a mistake.

PMID- 8283930
TI  - The effects of lowering serum cholesterol on coronary heart disease risk.
AB  - The clinical trials and angiographic studies of cholesterol lowering have been of
      decisive importance in persuading scientific and public opinion that elevated
      serum cholesterol is a causal element in the chain of events leading to CHD and
      that treatment by diet and drugs is effective in lowering the risk of CHD. The
      appropriateness of these opinions is well illustrated by the analyses of the
      combined trials, which show that the clinical event rate can be lowered by about
      20% if cholesterol levels are lowered by 10%. The reduced risk for CHD applies to
      both primary and secondary prevention. Further, the angiographic studies have now
      demonstrated that vigorous lipid-lowering therapy leads to improvements in the
      angiographic appearance of coronary vessels, which are accompanied by large
      reductions in CHD risk. Diet and a variety of drugs appear to modify the risk of
      CHD. The results of studies using combinations of drugs, for example, bile acid
      binding resins with either niacin or hydroxymethylglutaryl coenzyme A reductase
      inhibitors, are particularly impressive. The primary purpose of treatment remains
      the reduction of total and LDL cholesterol; however, the possibility of an
      additional benefit from improving other aspects of the lipid profile (such as
      raising HDL cholesterol levels) at the same time should not be ignored. In many
      instances, combinations of drugs are needed to achieve optimal lowering of serum
      cholesterol or to treat all elements of the disorder. Although the treatment of
      high-risk but apparently healthy individuals should not be neglected, it would be
      particularly appropriate to institute intensive diet and combination drug therapy
      in patients with existing CHD, in view of their high risk of reinfarction if left
      untreated. The secondary prevention trials provide evidence that clinical events
      can be reduced in such patients. The angiographic studies strongly suggest that
      large reductions in cholesterol to much lower levels (in-treatment LDL
      cholesterol levels below 100 mg/dL were frequently observed) than those achieved
      in the secondary prevention trials markedly reduce the rate of coronary events in
      patients with existing disease.

PMID- 8283931
TI  - Diet and lifestyle modification and its relationship to atherosclerosis.
AB  - Much of the CHD protective effects of diet are mediated through the effects of
      diet on risk factor levels. The best studied are the effects of diet on
      lipoprotein levels and blood pressure. With these effects in mind, specific
      dietary recommendations have been made to reduce CHD rates among healthy
      Americans. Dietary modification will reduce risk factor levels in the majority of
      people and will have measurable impact on CHD rates in the nation (Table 9). In
      the treatment of patients, it is important to distinguish which lipoprotein and
      blood pressure abnormalities are amenable to diet and which ones require drug
      therapy. This distinction can be made by understanding the quantitative
      relationship between dietary intake and risk factor levels that has been
      presented here and by assessing the current dietary intake of the individual.
      There must be a significant change in dietary composition to produce a
      significant change in risk factor level. This point, although it appears obvious
      when stated, is a common source of confusion concerning the efficacy of diet. For
      individuals, most nonresponse to dietary change reflects the lack of a dietary
      change. Poor adherence, in turn, may be the direct result of inadequate diet
      counseling. Counseling with a registered dietitian may be useful not only in
      educating the high-risk patient concerning the nutrient content of food, but also
      in establishing the current dietary intake of the patient. Compliance is not the
      only cause of nonresponse. For some patients who are already following a CHD
      prevention diet, additional risk factor reductions may not be evident when minor
      dietary constituents are altered. Because the majority of the diet effect has
      already been achieved, this "nonresponse" should not be surprising. The benefit
      of a change in a minor dietary constituent may not be detectable above the random
      day-to-day variation in risk factor levels. Lastly, although true nonresponders
      to diet have been observed, at least for blood cholesterol levels, the prevalence
      of nonresponse or minimal response is less than 10% of the population. Although
      the small changes in risk factor levels achieved by diet cannot compare with the
      greater changes achieved by drug therapy, dietary therapy will always have an
      important place in altering the health of the United States and its people. For
      some individuals, dietary and lifestyle modification may be all that is needed
      for CHD prevention; for others, dietary and lifestyle modifications provide a
      foundation on which drug therapy can be added for maximum CHD risk reduction.

PMID- 8283932
TI  - Familial lipoprotein disorders and premature coronary artery disease.
AB  - Although there is consensus that lipid variables, especially lipoprotein(a), are
      heritable and that elevated LDL cholesterol levels should be treated, there are
      no clear definitions of the common familial lipid disorders associated with
      premature CHD (lipoprotein(a) excess, FCH, familial dyslipidemia, familial
      hypoalphalipoproteinemia, familial hypercholesterolemia), nor do we have clear
      guidelines for the treatment of most of these disorders. Implementation of
      therapy for elevated LDL cholesterol in familial lipid disorders often has not
      occurred even in the United States. Before recommendations can be made for
      subjects with lipoprotein(a) excess and HDL deficiency (who often have combined
      hyperlipidemia or hypertriglyceridemia), prospective studies documenting benefit
      of CHD risk reduction must be carried out in subjects with lipoprotein(a) excess
      and HDL deficiency. One such study is being carried out with gemfibrozil in CHD
      patients with HDL deficiency. Current data do justify treatment of CHD patients
      with lipoprotein(a) excess with niacin because niacin has been shown to lower
      lipoprotein(a) levels as well as lower CHD risk mortality in random CHD patients.
      With regard to CHD patients with or without HDL cholesterol levels less than 35
      mg/dL (0.9 mmol/L), efforts should be made to optimize their lipid profile and
      reduce their LDL cholesterol levels to less than 100 mg/dL (2.6 mmol/L).

PMID- 8283933
TI  - Drug treatment of dyslipoproteinemia.
AB  - This article has focused on the appropriate indications for lipid-lowering drugs
      in adult patients with different lipoprotein disorders, which we have divided
      into primary hypercholesterolemia, combined hyperlipidemia,and
      hypertriglyceridemia. The mechanism of action, efficacy, and safety profile of
      the major drugs have been reviewed, and based on this information, we have
      presented our views on the appropriate drugs of first choice and appropriate
      second-choice agents for treatment of adult patients with different
      dyslipidemias. The rationale for the use of hypolipidemic drugs is strongest in
      patients with hyperlipidemia who concurrently have evidence for coronary or
      peripheral vascular disease, in whom the goal of secondary prevention is to
      retard further progression of atherosclerosis and potentially induce some
      regression, whereas in selected high-risk patients without evidence of
      atherosclerosis, the goals of therapy are to prevent the premature development of
      CAD or, in patients with severe hypertriglyceridemia, prevent the adverse
      sequelae of hepatomegaly, splenomegaly, and potentially pancreatitis. We have
      focused on the use of hypolipidemic drugs in adult patients, and the guidelines
      discussed are not appropriate for use in children with hyperlipidemia, in whom
      drug therapy should be undertaken selectively and in consultation with a lipid
      specialist. Many areas of controversy in the use of lipid-lowering drugs remain
      to be addressed by future studies; these include the use of lipid-lowering drugs
      in patients with secondary causes of hyperlipidemia (e.g., the nephrotic
      syndrome), the use of lipid-lowering drugs in women, and recommendations for drug
      therapy in older patients.

PMID- 8283934
TI  - Diagnosis and treatment of lipid disorders.
AB  - A brief summary of the revised NCEP guidelines for the detection, evaluation, and
      treatment of high blood cholesterol levels in adults is presented. The major
      changes in the current guidelines are the inclusion of three categories of CHD
      risk, one for secondary prevention and two for primary prevention based upon a
      combination of LDL-c levels and the number of other risk factors. Age and gender
      are now considered in the determination of risk factors. There is more emphasis
      on the treatment of postmenopausal women and individuals 65 years of age or older
      and less emphasis on drug treatment in younger patients. HDL-c measurements are
      now routine in screening in the clinical setting and drugs that both lower LDL-c
      and increase HDL-c levels can be considered in high risk patients. According to
      the current guidelines, approximately 29% of the adult population should receive
      dietary therapy and approximately 7% may be candidates for drug therapy.

PMID- 8283935
TI  - The biology of the artery wall in atherogenesis.
AB  - A great deal of progress has been made in the past few years in our understanding
      of the processes involved in atherogenesis and in mechanisms by which commonly
      accepted risk factors may affect these processes. These insights have allowed us
      to understand how various interventions may retard atherogenesis and decrease
      clinical events by improving plaque stability. The identification of new risk
      factors, such as lipoprotein(a), and of particular molecules that can be
      identified in atherosclerotic tissue, such as adhesion molecules, growth factors,
      cytokines, and proteins that regulate cholesterol uptake and removal, have
      identified several potential new targets for therapeutic intervention. Advances
      in molecular biologic techniques, including transgenic techniques, have markedly
      increased the types of potential interventions available. A major challenge for
      the future will be to determine which among this plethora of therapeutic
      possibilities holds the most promise for decreasing the morbidity and mortality
      associated with this disease.

PMID- 8283936
TI  - The prevention of cardiovascular disease. Emphasis on secondary prevention.
AB  - Atherosclerosis is a progressive disease affecting all major arteries. Clinical
      evidence of atherosclerosis increases the risk of subsequent morbid and mortal
      events fivefold to sevenfold over the next 5 to 10 years. The same risk factors
      contribute to the initial development of CVD events as to their recurrence. Both
      coronary and noncoronary events, such as stroke or PAD, reflect the severity of
      the underlying atherosclerotic process and strongly predict future excess CVD
      morbidity and mortality. Short-term and long-term survival depends on modifying
      the risk factors that contribute to CVD events. Although absolute proof of
      benefit for secondary prevention does not exist for all risk factors, the data
      from primary prevention trials and the secondary prevention trials that have been
      done argue strongly for aggressive intervention. Benefit has been demonstrated
      for smoking cessation, cholesterol reduction, and blood pressure control.
      Selected patients may benefit from additional medical, procedural, or surgical
      interventions to prolong life, such as beta-blocking agents, aspirin, or carotid
      endarterectomy. Many secondary prevention measures are a cost-effective way to
      reduce the substantial morbidity and mortality due to CVD. Contrary to primary
      prevention, even modest treatment effects from secondary prevention efforts can
      benefit large numbers of patients. Finally, secondary prevention may be more
      successful because patients with clinical evidence of CVD may be more highly
      motivated than their healthy counterparts to make and maintain lifestyle changes.

PMID- 8283937
TI  - Epidemiology of triglycerides, small dense low-density lipoprotein, and
      lipoprotein(a) as risk factors for coronary heart disease.
AB  - In addition to LDL cholesterol, triglyceride; small, dense LDL (LDL subclass
      phenotype B); and lipoprotein(a) are emerging as important risk factors for CHD.
      Elevated plasma levels of each of these risk factors have consistently been
      associated with increased risk of CHD in case-control studies of white patients.
      In prospective studies, however, the association between triglycerides and CHD is
      generally not independent of HDL cholesterol in multivariate statistical
      analyses. Although the data are scarce, studies in women show that triglycerides
      are a stronger risk factor for CHD in women than in men. Although no prospective
      studies of LDL subclass phenotype B have been reported, a number of potential
      atherogenic mechanisms may be responsible for the association with CHD seen in
      the case-control studies. Similarly, few prospective studies of lipoprotein(a)
      have been published, all in Scandinavian men. The observational studies generally
      show an association between elevated lipoprotein(a) and CHD in whites but not in
      blacks. Each of these risk factors also has a genetic component. Of the two
      familial forms of hypertriglyceridemia, FCH has been associated with familial CHD
      in two cross-sectional studies. LDL subclass phenotype B is inherited consistent
      with a single major gene effect, and candidate gene linkage studies are in
      progress to map the chromosomal location of this proposed gene. Finally,
      lipoprotein(a) levels are largely attributable to variation at the apo(a) locus
      on chromosome 6. Whether other genetic variations explain the lack of reported
      associations between lipoprotein(a) and CHD in black populations remains to be
      determined. Understanding of these "non-LDL" lipoprotein-related risk factors
      will provide important information for the development of new, effective
      intervention strategies for the prevention of CHD.

PMID- 8283938
TI  - [Surgical treatment of cavernous hemangiomas in the liver].

PMID- 8283939
TI  - [Laparoscopic hernia surgery--quo vadis?].

PMID- 8283940
TI  - Surgical treatment of cavernous haemangiomas of the liver.
AB  - Cavernous haemangiomas of the liver were surgically treated in 36 women and 14
      men over a 10-year period. The tumours were solitary in 42 cases and multiple in
      8. Locations were the right lobe in 39 cases, the left one in 5 and both lobes in
      6. The size of the tumours ranged from 0.4 to 14 cm in diameter. Enucleation of
      tumours was carried out in 29 cases, an atypical liver resection in 19 cases,
      anatomical lobectomy in 2 cases and a right trisegmentectomy in 1 case. There was
      no mortality. Morbidity rate seems to be lower in patients who underwent
      enucleation. The authors indicate the importance of enucleation for removal of
      liver haemangiomas of various sizes.

PMID- 8283941
TI  - [Laparoscopic hernia repair].
AB  - From January 1992 to February 1993 a total of 361 inguinal hernia repairs were
      performed in our unit. We routinely performed the Shouldice repair. In 60
      patients, 46 men and 14 women, 19-82 year old, we closed the inguinal defect with
      a patch, performing a "tension-free" repair by a laparoscopic technique. In 26
      patients we found a left-sided hernia, in 21 patients a right-sided, and in 13
      bilateral hernias. We found 29 direct hernias, 26 indirect hernias and 18
      combined hernias. There were no intraoperative complications. Postoperatively, 1
      patient suffered from epididymitis, and 5 patients reported disturbed sensibility
      of the skin at the medial proximal thigh for some weeks. One patient had an
      inguinal seroma postoperatively. In this patient we had not removed the hernia
      sac. There was no recurrence. Long time results are not available until now.

PMID- 8283942
TI  - [Inguinal hernia repair with local anesthesia--a comparative analysis].
AB  - Since February 1992 local anaesthesia has been routinely used for repair of
      inguinal hernias at the Surgical Department of the RWTU Aachen. All 607 patients
      undergoing Shouldice repair of primary inguinal hernia between January 1990 and
      March 1993 were retrospectively analysed with reference to need for analgesics,
      length of stay in hospital, and rate of complications. In addition, 50 patients
      treated with local anaesthesia and 50 patients treated under general anaesthesia
      underwent prospective pain analysis using a visual analogue scale and spirometric
      tests. Following local anaesthesia we found fewer need of analgesics, shorter
      stays in hospital, and less complications. The pain level was lower and
      ventilatory function was better. Repair of inguinal hernia with local anaesthesia
      is a safe method of lowering the risks involved in the operation and improving
      patient comfort without increasing complications.

PMID- 8283943
TI  - [Results of surgical therapy of bacterial sacroiliitis with primary arthrodesis].
AB  - Surgical treatment of pyogenic infections of the sacroiliac joint is indicated in
      cases of ineffective conservative treatment, abscess formation, septicemia, and
      neurological deficits. Between 1983 and 1990 in nine patients surgical treatment
      was performed for pyogenic sacroiliitis under this criteria. The surgical
      procedure included joint debridement, primary arthrodesis of the sacroiliac joint
      using a autologous bone graft, antibiotic therapy and postoperative
      immobilisation. Follow-up examination of 8 patients in average 47 months
      postoperatively revealed excellent functional and roentgenological results in 6
      patients. Two patients suffered only from mild low-back pain, none of the eight
      patients demonstrated signs of a recurrent infection, one patient died due to
      complications of a long-lasting preoperative septicemia. Regarding these
      postoperative follow-up results surgical therapy including primary sacroiliac
      arthrodesis should be early considered, because this treatment has a low
      complication rate and the surgical technique is easy to perform and results are
      excellent or good in most of the patients.

PMID- 8283944
TI  - [Rupture of the patellar ligament--a late complication after removal of a bone
      tendon-bone transplant as cruciate ligament replacement].
AB  - Ruptures of the patellar ligament have been observed in surgery for complete
      substitution of the knee joint and with application of the operation method
      according to Roux and Goldwilde; ruptures of this ligament after removal of a
      graft cruciate ligament substitution have been described very rarely. Since 1990
      we have been practicing the method of autologous substitution of the cruciate
      ligament by using material from the median part of the patellar ligament. In one
      patient treated by this method who had displayed no complications during 10
      months after the operation a new adequate trauma resulted in rupture of the
      patellar ligament at its tibial insertion. As far as we can assess on the basis
      of available technical literature, such injury might be due to problems of
      paraligamentary blood supply, partial or complete resection of the infrapatellar
      fatty tissue additionally contributing to lasting vascular damage.

PMID- 8283945
TI  - [Billroth I hemigastrectomy in complicated recurrent ulcer after selective
      proximal vagotomy].
AB  - The outcome of Billroth I hemigastrectomy for complicated recurrent ulcers after
      proximal selective vagotomy (PSV) for duodenal ulcer was analyzed in a
      retrospective study of 15 patients followed up for 15-81 months (mean 3.8 years)
      postoperatively. Bleeding was reported in 4, stenosis in 5, penetration in 3,
      perforation in 1 and refractory ulcer in 2 cases. None of the patients died
      during revision surgery, and none developed ulcer recurrence. In 4 patients
      complications were seen, including bleeding requiring relaparotomy (1) and
      subhepatic hematoma (3). In 12 patients (80%) a good or excellent result (Visick
      I/II) was seen at follow-up. Reasons for Visick III or Visick IV classification
      were reflux esophagitis grades I and II in 2 cases and refractory dyspeptic
      symptoms in 1 case. Distal gastric resection with a Billroth I anastomosis for
      complicated recurrent ulcer after PSV proved to involve only low morbidity and to
      effect reliable prophylaxis of ulcer recurrence in the long term.

PMID- 8283946
TI  - [Effects of carotid endarterectomy on various neuropsychologic parameters. A
      neuropsychologic longitudinal study].
AB  - Carotid endarterectomy was performed in 25 patients with symptomatic
      cerebrovascular disease. All patients underwent detailed neuropsychological
      investigations immediately before surgery, immediately after surgery, and again
      after a follow-up period of 14 months. Immediately after surgery the flicker
      fusion frequency was temporarily reduced, indicating an impairment of global
      cognitive functioning. Postoperatively, verbal attention was found to be
      improved, particularly in younger patients, in patients with TIA, and in patients
      with left-sided operation. Finally, visual retention (Benton) was improved at the
      end of the observation period, especially in older patients and in patients with
      left-sided operation. Considering the complexity of pathologic brain perfusion,
      the effects of carotid endarterectomy can only be explained if a multidimensional
      approach is adopted.

PMID- 8283947
TI  - [A three-year aid program for plastic surgery in Peshawar (Pakistan). Ongoing
      management of severely injured patients of the Afghanistan war: 1,528 large
      operations, 5,171 smaller interventions, 15,932 patients examined].
AB  - Since 1980 Interplast Germany has sent many plastic surgeons to developing
      countries. In 1989 a new Interplast Germany program for helping Afghan refugees
      in Pakistan's Peshawar was started. The Federal Republic of Germany financed the
      first two years; thereafter, the European Community and Help supported the
      project. Twenty-four teams with 123 nurses, surgeons and anesthesiologists
      operated on 1,528 patients in two hospitals. In the same period 5,171 smaller
      operations have been performed and 15,932 patients have been examined. Low
      expense for the teams, good support by officials, and professional administration
      have made this project highly effective for 3 years.

PMID- 8283948
TI  - [Computer-assisted surgery documentation in clinical routine practice].
AB  - In surgery, computer support is still of minor importance. It is the aim of this
      publication to outline the concept of a computer-assisted documentation system
      for surgical procedures, to describe the realization of the concept and to
      discuss the results of the evaluation. Planning of the system started in 1988
      with an analysis of existing computer support at our clinic, definition of the
      parameters to be documented and determination of the classifications to be used,
      followed by a design for the system's use and a decision on hardware and
      software. The system is run on an IBM-compatible personal computer with three
      terminals, and the software used is MEDOS. The surgical procedures are documented
      with a four-level hierarchical classification related to the VESKA code and the
      internal university codes. After extensive training of the doctors, routine use
      commenced in 1991. Up to now 9837 operations have been documented by 35 surgeons.
      The system produces all necessary statistics and supports scientific studies and
      inquiries from individual doctors. A prospective evaluation of 300 consecutive
      operations demonstrated good compliance of the doctors and high data quality. To
      achieve optimal benefit from the use of computers it is recommended that
      departmental communication and documentation systems be gradually built up in
      surgical departments.

PMID- 8283949
TI  - [Is adjuvant chemotherapy of colon cancers (Dukes C; TxN+) regarded as standard
      today?].

PMID- 8283950
TI  - Why are potential women being killed?

PMID- 8283951
TI  - Combining work with caring for children, findings from a longitudinal study of
      midwives' careers.
AB  - Facilities that enable women to combine work with caring for children are of
      particular importance to professions comprised primarily of women, such as
      midwifery. This article presents findings on four aspects of this topic obtained
      in the course of a 13-year longitudinal study of midwives' careers: the numbers
      who had children and had taken breaks for pregnancy and child care, opportunities
      for professional development during periods of child care; the effect of such
      breaks on career progression, and the importance of family commitments in
      relation to retention. The majority of both cohorts were single women in their
      twenties at the time that they qualified as midwives. During the course of the
      study more than half the respondents had children; pregnancy was cited as the
      main reason for leaving midwifery followed in later years by being unable to find
      posts with hours of work that could be combined with family commitments. Findings
      showed little evidence of employers keeping in touch with midwives during child
      care breaks about job opportunities and professional developments; the majority
      of respondents however, said that they would have welcomed such contact. In
      common with other work on women's careers, this study demonstrated that breaks
      for child care are associated with slower rates of promotion. A wide range of
      issues were identified by respondents as relevant to retention, with those
      relating to combining work and family rated consistently as among the most
      important. The study demonstrates the importance that should be accorded to this
      issue when overall policies to improve retention in midwifery are being
      considered.

PMID- 8283952
TI  - The contribution of professional support, information and consistent correct
      advice to successful breast feeding.
AB  - This paper presents qualitative and quantitative data on experiences of breast
      feeding in hospital from a national survey of pain relief in labour. Successful
      breast feeding was found to be significantly associated with satisfaction with
      medical care, help given with feeding by hospital staff, and the wish to have a
      subsequent baby in the same hospital. Information and support from staff were
      frequently mentioned as factors contributing to success. Lack of such help,
      receiving inaccurate or conflicting advice, and unsolicited and unwanted offers
      of artificial milk were major sources of discontent. Practical support could be
      improved by the provision of rooms furnished with nursing chairs where women
      could breast feed in comfort, benefiting from the companionship and experience of
      other women and the support of breast feeding counsellors. Efforts should be made
      to combat the problem of conflicting advice by ensuring that ward staff are
      conversant with up-to-date knowledge of best practices.

PMID- 8283953
TI  - An evaluation of consumer perspectives of childbirth and parenting education.
AB  - As part of a study of childbirth and parenting education in the Australian
      Capital Territory (O'Meara, 1993a; 1993b) an evaluation of clients' views of the
      service was undertaken. The evaluation sought to identify indicators of
      effectiveness and needs. Two independent groups (current and past users, n = 207)
      were surveyed using an original questionnaire based on predisposing, reinforcing
      and enabling factors for human behaviour (Green's PRECEDE model). The data were
      compared and analysed using the related t-test for indicative differences in
      perceptions of the two groups. Indicative differences that were statistically
      significant were compared on variables representing users' age, parity and
      preferred mode of childbirth education (public or private). No evidence was found
      of significant differences in attitudes, beliefs and values before and after
      birth attributable to childbirth education. However, the health skills,
      confidence and emotional preparation for the birth, and the extent of
      participation in the learning process did not fully measure up to users'
      expectations. Consumers expect professionalism in the provision of services, with
      course content specifically tailored to their learning needs, taking into account
      age and previous experience of childbirth. A comprehensive curriculum is
      suggested covering all stages of the childbirth process from prepregnancy to
      parenting.

PMID- 8283954
TI  - Amnihook versus amnicot for amniotomy in labour.
AB  - In a study of 100 women in established labour we investigated two devices
      currently used for amniotomy, the Amnihook, a long rigid instrument and the
      Amnicot, a finger stall with a plastic hook on the end. No overall difference was
      found in operator ease of use or maternal discomfort. There were significantly
      fewer babies with long scratches p = 0.02, Odds ratio 0.19 (95% CI 0.05 to 0.68)
      and the mean scratch length was almost halved in the Amnicot group (p < 0.05, 95%
      CI for difference between means 0.653 to 6.71). Our findings support the
      theoretical advantage of a reduction in fetal scalp trauma using a flexible
      device for amniotomy.

PMID- 8283955
TI  - Relationships between baby feeding types and patterns, gut transit time of
      meconium and the incidence of neonatal jaundice.
AB  - The incidence of neonatal jaundice is reported to have increased in relation to
      breast feeding and various factors are thought to contribute to this either
      singularly or in concert. In a group of 150 full-term healthy babies, feeding
      types and gut transit time of meconium were examined. The findings demonstrated
      significant differences between feeding types and time taken to evacuate total
      meconium (p < 0.0001), weight loss/gain patterns (p < 0.0005) and the incidence
      of moderately severe jaundice (p < 0.01) during the early neonatal period. Baby
      feeding types were clearly defined in the study and a stool colour comparator was
      used to facilitate identification and classification of all stool colour
      transition from meconium through to yellow. Maximum weight loss was found to
      occur on the second day after delivery and in many instances the lost weight was
      regained by the baby on the fifth day. Exceptions to this were babies who fed
      ineffectively or inadequately. These outcomes suggest that the assistance and
      advice given to mothers and babies, by midwives and others, to achieve effective
      feeding practices in the days following birth is of paramount importance to the
      baby's immediate wellbeing.

PMID- 8283956
TI  - Cisapride for nocturnal heartburn.

PMID- 8283957
TI  - Extended-release isosorbide mononitrate for angina.

PMID- 8283958
TI  - Bacterial pathogens, from adherence to invasion: comparative strategies.

PMID- 8283959
TI  - Ultrastructural localization of urease of Helicobacter pylori.
AB  - Helicobacter pylori urease was characterized by means of an enzyme histochemical
      electron microscopic technique. Ultrastructural analysis revealed no urease
      activity in one strain; in seven H. pylori strains (43.75%), urease activity was
      associated with the cell membrane. Eight strains (50.0%) showed reaction product
      located within the cytoplasm. Urease activity showed no correlation with
      localization of activity. Our results demonstrate that H. pylori urease is not
      uniform in all H. pylori strains, and differences in activity and localization of
      urease activity may account for different virulence activities.

PMID- 8283960
TI  - An immunodominant 30-kDa antigen of a candidate anti-leprosy vaccine,
      Mycobacterium w, shares T and B cell determinants with M. leprae and M.
      tuberculosis.
AB  - Earlier we reported that vaccination of leprosy patients with Mycobacterium w
      induces an immune response directed predominantly against low molecular weight
      antigens. One of these antigens, with a molecular mass of 30-kDa, was recognized
      by a majority of the vaccinated subjects as well as the tuberculoid leprosy
      patients and healthy contacts. In the present communication we report further
      characterization of this antigen. Immunofluorescence and Western blot studies
      with antibodies raised against this antigen demonstrate that it is associated
      with the cell surface and has homologues present in M. leprae and M.
      tuberculosis. Delayed-type hypersensitivity studies carried out in guinea pigs
      immunized with the 30-kDa antigen show that in addition to sharing B cell
      determinants, this immunodominant antigen of M. w also shares T cell determinants
      with M. leprae and M. tuberculosis.

PMID- 8283961
TI  - Recombinant immunoblot in the serodiagnosis of Lyme borreliosis. Comparison with
      indirect immunofluorescence and enzyme-linked immunosorbent assay.
AB  - A recombinant immunoblot was developed for detection of IgM and IgG antibodies in
      patients with Lyme borreliosis. The recombinant antigens were the chromosomal
      encoded Borrelia burgdorferi proteins p100, the flagellin and an internal
      flagellin fragment thereof as well as the plasmid-encoded outer surface proteins
      A (OspA) and C (OspC). A panel of 144 sera from patients with Lyme borreliosis
      (erythema migrans, n = 31; neuroborreliosis state II, n = 60; Lyme arthritis, n =
      24 and acrodermatitis chronica atrophicans, n = 19) have been investigated and
      the results have been compared to the immunofluorescence absorption test (IFA
      ABS) and to two different enzyme-linked immunosorbent assays [the flagellin ELISA
      and a newly developed ELISA (OGP-ELISA)]. The two ELISAs were comparable in
      sensitivity, whereas the IFA-ABS was less sensitive for IgM antibody but equally
      sensitive for IgG antibody detection. Immunoblot analysis revealed that IgG
      antibodies are mainly reactive with p100 and the internal flagellin fragment
      (sensitivity 51% and 32%, respectively) and rarely with OspC (14%). All patients
      with late Lyme borreliosis had IgG antibodies against the p100. IgM antibodies
      were predominantly directed against OspC (43%) and in a lower extent against the
      internal flagellin fragment and p100 (15% and 13%, respectively). The complete
      flagellin was not useful due to a high number of unspecific reactions with
      control sera and the OspA was only exceptionally reactive in Lyme borreliosis
      patients. The sensitivity of IgM antibody detection could be increased in cases
      with early Lyme borreliosis from 46% to 65% when the OspC blot was performed in
      addition to the flagellin ELISA, or from 56% to 65% when performed in addition to
      the OGP-ELISA. The recombinant blot is, therefore, a valuable diagnostic test to
      increase sensitivity of early antibody detection and is regarded as a valuable
      confirmatory test also in late disease.

PMID- 8283962
TI  - Analysis of virus-specific RNA species and proteins in Freon-113 preparations of
      the Borna disease virus.
AB  - Treatment of homogenates from Borna disease virus (BDV)-infected brain tissue or
      cell cultures with Freon-113 yielded infectious particles with a buoyant density
      of 1.16-1.22 g/ml. Positive- and negative-stranded BDV-specific RNA species as
      well as three virus-specific proteins, known to be present in BDV-infected cell
      extracts, were demonstrated in these Freon-treated fractions. When the Freon
      purified virus preparations were treated with RNase A prior to RNA extraction,
      only negative-stranded, genomic RNA was detected in Northern blot hybridizations
      using sense and antisense RNA probes. These data substantiate that BDV is a
      negative-stranded RNA virus.

PMID- 8283963
TI  - Deaths resulting from firearm- and motor-vehicle-related injuries--United States,
      1968-1991.
AB  - Injury is the leading cause of death for persons aged 1-44 years in the United
      States. More than half (55%) of all injury-related deaths are caused by motor
      vehicles and firearms. Although the number of deaths from motor-vehicle crashes
      has exceeded those from firearms, since 1968, differences in the number of deaths
      have declined: from 1968 through 1991, motor-vehicle-related deaths decreased by
      21% (from 54,862 to 43,536) while firearm-related deaths increased by 60% (from
      23,875 to 38,317). Based on these trends, by the year 2003, the number of firearm
      related deaths will surpass the number of motor-vehicle crashes, and firearms
      will become the leading cause of injury-related death (Figure 1). This report
      compares trends and patterns of deaths resulting from firearm- and motor-vehicle
      related injuries in the United States from 1968 through 1991.

PMID- 8283964
TI  - Abortion surveillance: preliminary data--United States, 1991.
AB  - For 1991, CDC received data about legal induced abortions from 52 reporting areas
      (the 50 states, New York City, and the District of Columbia). This report
      presents preliminary data for 1991.

PMID- 8283965
TI  - Hantavirus pulmonary syndrome--United States, 1993.
AB  - In June 1993, a newly recognized hantavirus was identified as the etiologic agent
      of an outbreak of severe respiratory illness (hantavirus pulmonary syndrome
      [HPS]) in the southwestern United States. Since this problem was recognized,
      sporadic cases have been identified from a wide geographic area in the western
      United States. This report summarizes the epidemiologic characteristics of HPS
      cases reported to CDC from May 1 through December 31, 1993.

PMID- 8283966
TI  - Subcellular distribution and properties of rabbit liver aminoacyl-tRNA
      synthetases under myocardial ischemia.
AB  - Subcellular distribution of aminoacyl-tRNA synthetase activities has been studied
      in normal rabbit liver and under experimental myocardial ischemia (EMI). An
      increase in the activity of a number of aminoacyl-tRNA synthetases in
      postmitochondrial and postribosomal supernatants from rabbit liver has been
      determined 12 hr after EMI. Gel chromatography of the postribosomal supernatant
      on Sepharose 6B shows that aminoacyl-tRNA synthetase activities are distributed
      among the fractions with M(r) 1.82 x 10(6), 0.84 x 10(6) (high-M(r) aminoacyl
      tRNA synthetase complexes) and 0.12-0.35 x 10(6). In the case of EMI aminoacyl
      tRNA synthetase activities are partly redistributed from the 1.82 x 10(6) complex
      into the 0.84 x 10(6) complex. The catalytic properties of both free and complex
      leucyl-tRNA synthetases have been compared. KM for all the substrates are the
      values of the same order in norm and under EMI. A decrease in some aminoacyl-tRNA
      synthetase activities associated with polyribosomes has been observed 12 hr after
      EMI. The interaction of aminoacyl-tRNA synthetases with polyribosomes stimulates
      the catalytic activity of some enzymes and protects them from heat inactivation
      in vitro. It is assumed that the changes in association of aminoacyl-tRNA
      synthetases with high-M(r) complexes and compartmentalization of these enzymes on
      polyribosomes may be related to the alteration of protein biosynthesis under
      myocardial ischemia.

PMID- 8283967
TI  - Effect of stress on the antioxidant enzymes and gastric ulceration.
AB  - The effect of cold-restraint stress on the antioxidant enzymes of the rat gastric
      mucosa was studied with a view to finding out their role in stress induced
      gastric ulceration. Histological examination revealed stress induced extensive
      damage of the surface epithelial cell with lesions extending up to submucosa in
      some cases. Stress causes time-dependent increase in histamine and pepsin content
      but decrease in acid content of the gastric fluid with the progress of ulceration
      (ulcer index) for two hours. The tissue lipid peroxidation was significantly
      increased as evidenced by accumulation of malondialdehyde. Since lipid
      peroxidation results from the generation of reactive oxygen species, stress
      effect was studied on some antioxidant enzymes such as superoxide dismutase,
      peroxidases and prostaglandin synthetase as a function of time. The time
      dependent increase in stress ulcer correlates well with the concomitant increase
      in superoxide dismutase activity and decrease in peroxidase and prostaglandin
      synthetase activity. This creates a favourable condition for accumulation of
      endogenous H2O2 and more reactive hydroxyl radical (OH.). Administration of
      antioxidants such as reduced glutathione or sodium benzoate prior to stress
      causes significant decrease in ulcer index and lipid peroxidation and protection
      of gastric peroxidase activity suggesting the involvement of reactive oxygen
      species in stress induced gastric ulceration. This is supported by the in vitro
      observation that OH. can also inactivate peroxidase and induce lipid
      peroxidation. As prostaglandin is known to offer cytoprotection, stress-induced
      loss of prostaglandin synthetase activity appears to aggravate the oxidative
      damage caused by reactive oxygen species.

PMID- 8283968
TI  - Cloning and analysis of the human myocardial Na+/H+ exchanger.
AB  - The Na+/H+ exchanger is an integral membrane protein that is universally
      distribute in mammalian tissues and is responsible for intracellular pH
      regulation. Several isoforms of the Na+/H+ exchanger exist (NHE-1-NHE-4). The
      first that was cloned is the amiloride sensitive isoform (NHE-1). Using a
      fragment of the rabbit cardiac Na+/H+ exchanger cDNA clone we isolated and
      sequenced Na+/H+ exchanger cDNA from a human heart coding for the complete human
      Na+/H+ exchanger (NHE-1 isoform). Two overlapping cDNA clones were obtained,
      giving a combined sequence that contained both 3' and 5' untranslated regions.
      The 5' and 3' untranslated regions proved to be highly homologous to human
      sequences described earlier but contained some variations that could affect the
      mRNA stability and/or the efficiency of translation of the Na+/H+ exchanger.
      Northern blot analysis and reverse transcriptase polymerase chain reaction
      confirmed the presence of the 5 kb NHE-1 message in primary cultures of isolated
      myocytes.

PMID- 8283969
TI  - Modulation of allo-immune responses in vivo and in vitro by sperm specific
      lactate dehydrogenase-C4.
AB  - The role of sperm specific lactate dehydrogenase-C4 (LDH-C4) in allo-immune
      responses using mixed lymphocyte cultures (MLC) and cytotoxic T cell (CTL)
      generation in vitro and local graft versus host (LGVH) reaction and allograft
      enhancement in vivo has been ascertained. LDH was purified from testes (LDH-C4)
      and kidney (LDH-B4) of C57Bl/Ks mice. MLC and CTL were performed using C57Bl/Ks
      anti A/J lymphocytes in presence of 10(-3)-1 micrograms LDH-B4 or LDH-C4 per
      culture. The MLC and CTL responses showed biphasic action depending on the dose
      of LDH-C4. Early MLC culture gave significantly low stimulation index at 10(-2)
      10(-1) micrograms LDH-C4 as compared to non-treated control cultures. However,
      the MLC response in presence of LDH-C4 was not different from the LDH-B4 treated
      one which showed a similar biphasic trend. On the other hand, 51Cr release from
      YAC-222 target cells was practically abolished by LDH-C4 at 10(-3)-1(-1)
      micrograms, and this was strikingly different from LDH-B4 or non-treated
      cultures. LGVH reactivity as performed by using C57Bl/Ks lymphocytes along with
      LDH-C4 in (C57Bl/Ks x A/J) F1 hybrids indicated a suppression of stimulation
      index in primary and secondary (i.e. preimmunized in presence of LDH-C4 or LDH
      B4) LGVH. Allograft enhancement of Sa I (A/J) in C57Bl/Ks mice in presence of LDH
      C4, was delayed slightly but significantly during primary or secondary
      transplantation reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8283970
TI  - Interaction of cycloalkanoprogesterones with mammalian progesterone receptor:
      binding of pregna-D'-pentaranes in the calf uterine cytosol.
AB  - Pregna-D'-pentaranes (pentaranes) are modified progesterones with demonstrable
      progestational activity and contraceptive effect. We have examined the steroid
      binding characteristics of the two newly synthesized progesterone analogs,
      Pentarane A (16 alpha, 17 alpha-cyclohexanoprogesterone) and Pentarane B (6 alpha
      methyl, 16 alpha, 17 alpha-cyclohexanoprogesterone), and studied the nature of
      their interaction with progesterone receptor (PR) from the chicken oviduct and
      the calf uterine cytosols. Pregna-D'-pentaranes exhibited no affinity for the
      chick PR but interacted with the calf uterine PR as did R5020. The pentaranes,
      however, bound PR less tightly. R5020- or pentarane-bound PR sedimented as an 8S
      moiety in 8-30% linear glycerol gradients. Thermal transformation of receptor
      resulted in the reduction of the 8S form, and caused an increase in the binding
      of R5020- and progesterone-bound PR complexes to DNA-cellulose. The pentarane
      bound PR bound poorly, if at all, to DNA-cellulose. Our data suggest that
      pentaranes exhibit both similarities and differences with natural and synthetic
      progestins with respect to their interaction with calf uterine PR. The lack of
      pentarane binding to chicken PR is reminiscent of the general phenomenon that
      antiprogestins (RU486, ZK98299, and Org 31710 and Org 31806) do not interact with
      chicken PR. Pentaranes, therefore, represent unique steroid analogs to
      investigate the molecular mechanism of steroid hormone action.

PMID- 8283971
TI  - Modification of contractile proteins by oxygen free radicals in rat heart.
AB  - This study was undertaken to investigate the effects of oxygen free radicals on
      myofibrillar creatine kinase activity. Isolated rat heart myofibrils were
      incubated with xanthine+xanthine oxidase (a superoxide anion radical-generating
      system) or hydrogen peroxide and assayed for creatine kinase activity. To clarify
      the involvement of changes in sulfhydryl groups in causing alterations in
      myofibrillar creatine kinase activity, 1) effects of N-ethylmaleimide (sulfhydryl
      groups reagent) on myofibrillar creatine kinase activity, 2) effects of oxygen
      free radicals on myofibrillar sulfhydryl groups content, and 3) protective
      effects of dithiothreitol (sulfhydryl groups-reducing agent) on the changes in
      myofibrillar creatine kinase activity due to oxygen free radicals were also
      studied. Xanthine+xanthine oxidase inhibited creatine kinase activity both in a
      time- and a concentration-dependent manner. Superoxide dismutase (SOD) showed a
      protective effect on the depression in creatine kinase activity caused by
      xanthine+xanthine oxidase. Hydrogen peroxide inhibited creatine kinase activity
      in a concentration-dependent manner; this inhibition was prevented by the
      addition of catalase. N-ethylmaleimide reduced creatine kinase activity in a dose
      dependent manner. The content of myofibrillar sulfhydryl groups was decreased by
      xanthine+xanthine oxidase; this reduction was prevented by SOD. Furthermore, the
      depression in myofibrillar creatine kinase activity by xanthine+xanthine oxidase
      was protected by the addition of dithiothreitol. Oxygen free radicals may inhibit
      myofibrillar creatine kinase activity by modifying sulfhydryl groups in the
      enzyme protein. The reduction of myofibrillar creatine kinase activity may lead
      to a disturbance of energy utilization in the heart and may contribute to cardiac
      dysfunction due to oxygen free radicals.

PMID- 8283972
TI  - Regucalcin modulates hormonal effect on (Ca(2+)-Mg2+)-ATPase activity in rat
      liver plasma membranes.
AB  - The interaction of various hormones and regucalcin on (Ca(2+)-Mg2+)-ATPase
      activity in rat liver plasma membranes was investigated. The presence of
      epinephrine (10(-6)-10(-4) M), phenylephrine (10(-6)-10(-4) M), and insulin (10(
      8)-10(-7) M) in the reaction mixture produced a significant increase in (Ca(2+)
      Mg7+)-ATPase activity, while the enzyme activity was decreased significantly by
      calcitonin (3 x 10(-8)-3 x 10(-6) M). These hormonal effects, except for
      calcitonin, were clearly inhibited by the presence of vanadate (10(-4) M) which
      can inhibit the Ca(2+)-dependent phosphorylation of enzyme. Meanwhile, regucalcin
      (0.25 and 0.50 microM), isolated from rat liver cytosol, elevated significantly
      (Ca(2+)-Mg2+)-ATPase activity in the plasma membranes, although this elevation
      was not inhibited by vanadate (10(-4) M). The epinephrine (10(-5) M) or
      phenylephrine (10(-4) M)-induced increase in (Ca(2+)-Mg2+)-ATPase activity was
      disappeared in the presence of regucalcin; in this case the effect of regucalcin
      was also weakened. However, the inhibitory effect of calcitonin (3 x 10(-6) M)
      was not weakened by the presence of regucalcin (0.5 microM). Moreover, GTP (10(
      5) and 10(-4) M)-induced increase in (Ca(2+)-Mg2+)-ATPase activity was not seen
      in the presence of regucalcin (0.25 microM). The present finding suggests that
      the activating mechanism of regucalcin on (Ca(2+)-Mg2+)-ATPase is not involved on
      GTP-binding protein which modulates the receptor-mediated hormonal effect in rat
      liver plasma membranes.

PMID- 8283973
TI  - Myocardial expression of atrial natriuretic factor gene in early stages of
      hamster cardiomyopathy.
AB  - Ventricular cardiomyocytes represent the most important source of atrial
      natriuretic factor (ANF) in pathological conditions such as congestive heart
      failure (CHF). It has been suggested that in cardiomyopathic Syrian hamster
      ventricles the ANF gene can be reactivated during the hypertrophic stage
      occurring before heart failure. The present study was undertaken to investigate
      ANF gene expression during early stages of myocardial damage and its distribution
      throughout atrial and ventricular myocardium in UM-X7.1 cardiomyopathic Syrian
      hamsters (CMPH) before hypertrophy and cardiac failure occur. Atria, right and
      left ventricles, and interventricular septum of hearts of 20-23 days old (young)
      and 90-95 days old (adult) CMPH were studied. The absence of hypertrophy and
      cardiac failure was preliminarly ascertained by microscopic and hemodynamic
      evaluation. ANF-mRNA as well as tissue and plasma immunoreactive ANF were
      assayed. Moreover, ANF secretion pattern was evaluated by immunocytochemical
      techniques. Young and adult CMPH hearts were in the necrotic stage of myocardial
      disease, as demonstrated by histopathological evaluation and by decreased wet
      weights (mg/g body weight) of different heart regions. Hemodynamic assessment
      showed no significant changes of left ventricular end-diastolic pressure (LVEDP)
      and a decrease of the left ventricular peak systolic pressure (LVSP) and +dP/dt.
      Plasma immunoreactive ANF (IR-ANF) levels were higher in young (3-fold) and adult
      (6-fold) CMPH than in age-matched normal hamsters. A reduced IR-ANF concentration
      (per milligram protein) was observed in both young and adult cardiomyopathic
      atria in respect to healthy controls, whereas a higher IR-ANF concentration was
      present in ventricles. A 3-fold, 6-fold and 20-fold increase of IR-ANF
      concentration was found in right ventricular free-wall (RV), left ventricular
      free-wall (LV) and interventricular septum (IVS), respectively. Northern-blot
      analysis confirmed that IVS was the major site of ventricular ANF-mRNA
      transcription in both young and adult CMPH. ANF-mRNA was increased also in atria
      where a faster peptide secretion can be hypothesized to lower tissue IR-ANF
      concentration. ANF secretion in ventricular myocardium was achieved via
      constitutive pathway as demonstrated by immunocytochemistry. Different patterns
      of ANF gene reactivation occur in CMPH myocardium before intraventricular
      pressure increases and structural hypertrophic modifications are detectable. The
      extent of ANF gene reactivation in CMPH ventricles parallels the severity of
      necrotic damage. Moreover, ANF gene expression is heterogeneously distributed
      throughout the myocardium, suggesting that interventricular septum, the
      ontogenically youngest heart region, might preserve foetal characters which can
      be rapidly reactivated in pathological conditions.

PMID- 8283975
TI  - [Variability of the heterochromatic regions of the eukaryotic genome in
      connection with their possible biological role (based on the example of
      Drosophila melanogaster)].
AB  - Heterochromatin in the genomes of higher eukaryotes carrying repeated DNA
      sequences comprises up to 30-50% of the total DNA content. Repeated elements
      (satellites, retrotransposons, and tandemly repeated genes) in heterochromatin of
      D. melanogaster are considered in respect of their amplification resulting in
      pronounced biological effects. These elements were coined as "egoistic DNA" whose
      amplification may be restricted as a result of unknown types of interactions with
      the host genome. Correlations of the extent of amplification of heterochromatin
      elements with the fitness of individuals, reproductivity, and capability to
      transmit to the progeny a chromosome carrying the amplified heterochromatic
      region are discussed. The possible dependence of the genotypic structure and the
      fate of population in successive generations on the events of amplification of
      repeated heterochromatic elements in parental genomes is accentuated. In other
      words, "intragenomic population processes" driven by the amplification of several
      types of repeats ("egoistic DNA") must be taken into account when considering the
      dynamics of biological events in the course of propagation of individuals in a
      population.

PMID- 8283974
TI  - Expression of antioxidant enzymes in rat kidney during ischemia-reperfusion
      injury.
AB  - The effect of ischemia-reperfusion on activity, protein and m-RNA levels of
      catalase, copper-zinc and manganese containing superoxide dismutases and
      glutathione peroxidase, the enzymes that are involved in free radical
      detoxification was studied in rat kidney. Ischemia alone did not alter either the
      activities or protein levels of superoxide dismutase and glutathione peroxidase.
      However, catalase activity was found to be inhibited to 82% of control. The
      inhibition of catalase was due to the inactivation of the enzyme as there was no
      significant change in enzyme protein level. Reperfusion following ischemia,
      however, led to a significant decrease in both the activities as well as the
      protein levels of all the antioxidant enzymes. The observed overall decrease in
      total superoxide dismutase activity was the net effect of a decrease in copper
      zinc superoxide dismutase while manganese superoxide dismutase activity was found
      to be increased following reperfusion. This observed increase manganese
      superoxide dismutase activity was the result of its increased protein level. The
      mRNA levels for catalase, superoxide dismutases, and glutathione peroxidase were
      observed to be increased (100-145% of controls) following ischemia; reperfusion
      of ischemic kidneys, however, resulted in a significant decrease in the levels of
      mRNAs coding for all the enzymes except manganese superoxide dismutase which
      remained high. These results suggest that in tissue, the down regulation of the
      antioxidant enzyme system could be responsible for the pathophysiology of
      ischemia-reperfusion injury.

PMID- 8283976
TI  - [Evidence of the existence of hemolysin II from Bacillus cereus: cloning the
      genetic determinant of hemolysin II].
AB  - The hemolysin genetic determinant distinct from cereolysin AB genetic determinant
      (lecithinase and sphingomyelinase genes) has been cloned in Escherichia coli and
      Bacillus subtilis cells as an EcoRI fragment (2.9 kb) of Bacillus cereus VKM-B771
      chromosome DNA. The hemolytic product encoded by the cloned DNA fragment
      possessed all the properties of hemolysin II known to date: it was not inhibited
      by cholesterol, exhibited the Arrhenius effect, and had a relatively long (in
      comparison with cereolysin) lag period in erythrocyte lysis. The cloned DNA
      fragment was concluded to contain the gene of hemolysin II from B. cereus. In
      contrast to previous suggestions that hemolitic activity ascribed to hemolysin II
      is due to the combined action of sphingomyelinase and lecithinase, the results
      obtained present convincing evidence that hemolysin II is an independent B.
      cereus hemolytic factor different from cereolysin AB.

PMID- 8283977
TI  - [A model of positive rRNA gene expression regulation based on complementary
      interaction of transcripts of the prealbumin gene introns with its promotors].
AB  - The present paper is concerned with computation of the homology between the
      promoter and spacer sequences of the rRNA gene and the prealbumin introns. Both
      the sense and antisense strands of the promoters were compared with the introns.
      The rRNA promoters were found to contain a considerable number of prealbumin
      homologous intron sites on the coding strand only, whereas the spacer sequence
      had the intron-homologous sites on both strands. The fragments homologous to the
      ribosome gene promoter regions are mainly concentrated in the first prealbumin
      intron. The oncogene, glycoprotein and the interleukin intron fragments revealed
      no sites homologous to the ribosome gene promoter. A model has been proposed for
      positive regulation of the rRNA gene expression via complementary interaction
      between the transcripts of the prealbumin gene introns with sense and antisense
      strands of the rRNA promoters. It is believed that either positive or negative
      regulation of the ribosome biogenesis can be achieved in this way.

PMID- 8283978
TI  - [Study of the interaction of DNA with manganese ions by IR-spectroscopy].
AB  - DNA complexed with Mn2+ ions in films is studied at different relative humidities
      and ion contents ([Mn2+]/[P] = 0.4-1) by IR spectroscopy. It is shown that
      substantially more sorbed water molecules are necessary for the transition of DNA
      complexed with Mn2+ ions into the double helical conformation (preferentially B
      form) that for macromolecules in the absence of ions. DNA-Mn2+ complexes
      ([Mn2+]/[P] = 1) are able to absorb more water molecules than DNA. The results of
      the work evidence Mn2+ ion interaction with phosphates and nitrogen bases of the
      macromolecule: N7G, O6G.

PMID- 8283979
TI  - [Study of the structure-activity organization of the variola virus genome. II.
      Analysis of the nucleotide sequence of the HindIII region (C,E,R,Q,K and H)-DNA
      fragments of the India-1967 strain].
AB  - Sequencing of variola virus (VAR) genome region of 43069 bp was carried out. This
      area contains 42 potential genes. Computer analysis of proteins coding for these
      viral genes was done. We compared VAR proteins with the those of vaccinia virus.
      The region studied is conservative for orthopoxviruses.

PMID- 8283980
TI  - [Structure-activity analysis of ribonuclease A and related proteins].
AB  - A detailed analysis of noncovalent interactions in the RNase A molecule was
      carried out. For this purpose, contact maps based on structural data were
      constructed. Three hydrophobic nuclei and five microclusters were identified, and
      their quantitative parameters were calculated. The contacts between amino acid
      residues of the active center and the hydrophobic nuclei were established. The
      distribution of the charged amino acid residues on the of RNase A surface was
      shown. The data obtained was discussed in the context of the ribonuclease A
      family. The substitutions seen from the alignment of amino acid sequences in the
      family might have influence on the spatial structure of different parts of RNase
      A and their mutual orientation and, consequently on the biological activity of
      family members.

PMID- 8283981
TI  - [The hierarchy of complexes and compact structures of trivaline with nucleic
      acids. III. Complexes of trivaline with trinucleotides forms a rod-like structure
      with length of about 1000 A in solution].
AB  - We demonstrated the ability of trivaline in the course of interaction with
      certain trinucleotides in solution to form extended fibre-like structures with
      lengths of up to several thousand angstroms. Such structures were observed for
      complexes of trivaline with both deoxyribo- and ribonucleotides with homopurine,
      homopyrimidine, or random sequences, with or without terminal 5'-phosphate. A
      model of organization of such structures is proposed. It is based on tetramer
      complex of trivaline with short nucleotides, two structural units of which,
      consisting of trivaline tetramer and two trinucleotides, form the octamer
      complex. It has three perpendicular axes of symmetry of the second order. The
      spatial location of bases in this structure is additionally fixed by
      nucleopeptide interactions. The latter create favourable conditions for arranging
      hydrogen bonds between trinucleotides belonging to different tetramer complexes
      and stacking interactions between the bases of each nucleotide. Octamer complexes
      are able to form regular aggregates in the form of a "stack", consisting of
      dozens of elementary units. These aggregates can be electron microscopically
      visualized as extended fibre-like structures.

PMID- 8283982
TI  - [Analysis of peptide fragment insertions in the basic proteins of the
      bacteriophage M13, f1, and fd envelopes. Interconnection of structural
      characteristics of the envelope protein and viability of mutant phages].
AB  - An analysis of 12 peptide fragment insertions into the major coat protein
      (protein pVIII) of bacteriophages M13, f1 and fd has been done. To elucidate the
      relations between protein structural characteristics and viability of mutant
      phages, we used the program Pro-Anal. Correlations were found between phage
      viability and different physicochemical and structural characteristics of protein
      N-termini. Thus peptide insertions in nonviable phages have high indexes of alpha
      helicity, volumes, and polarity as well as high moments (alpha-helical and beta
      structural) of isoelectric point. On the other hand, high beta-turn indexes are
      correlated with viability. The most important factor which determines phage
      viability is the lack of positively charged amino acid residues on the C-terminal
      ends of peptide insertions. The correlations found hold for the pVIII proteins of
      four related phages-M13, IKe, If1 and I2-2. Based on these results, the rule of
      obtaining viable mutant phages with insertions in the major coat protein is
      suggested. A new site is described for peptide insertions--upstream of the first
      amino acid residue of the mature protein sequence.

PMID- 8283983
TI  - [Isolation of DNA polymerase beta from human placenta and study of its substrate
      specificity].
AB  - A method of purification of DNA polymerase beta with a specific activity of 1300
      units/mg from human placenta was developed. The enzyme preparations do not
      contain any other DNA polymerase activities and any nuclease contaminations
      degrading nucleic acids. On the basis of analysis of several standard parameters
      we conclude that the purified enzyme is polymerase beta. The optimal conditions
      of polymerization were established, and a comparison of the relative rates of
      polymerization with various template-primer complexes was carried out. Activated
      DNA was shown to be the optimal substrate in the presence of MgCl2, and
      poly(dA).oligo(dT) in the presence of MnCl2. The activation energies of
      polymerization for different template-primers were estimated.

PMID- 8283984
TI  - [Recognition of primers, containing noncomplementary nucleotides and units,
      lacking bases, by the Klenow fragment of Escherichia coli DNA polymerase I].
AB  - A comparison was carried out for the Km and maximal rates of conversion on (Vmax)
      with primers containing noncomplementary bases, as well as primers without
      several bases, and fully complementary primers of the same length. The number of
      complementary bases from the 3' end to the noncomplementary nucleotide was shown
      to determine the efficiency of interaction (and conversion) of the primers
      containing noncomplementary bases with enzyme. The DNA polymerase practically
      does not discriminate between the primers without one or two bases and the fully
      complementary primers. Elimination of one base in any position from the 3' end of
      the primer is equivalent to shortening of the primer by one nucleotide unit, and
      leads to a decrease in the affinity by a factor of 1.8. We suppose that DNA
      polymerase does not participate in primer mistake correction during the repair
      process if the DNA contains apurinic or apyrimidinic nucleotide units.

PMID- 8283985
TI  - [Recognition of T-T cyclobutane pyrimidine dimers in the form of primers by DNA
      polymerases].
AB  - A study was made of the efficiency of primer conversion catalyzed by human
      placenta DNA polymerase on the length of primer. The dependence of -log Kd and
      Vmax on the number of mononucleotide units (n) of primer were shown to be linear
      up to n <--> 10. Each mononucleotide unit of the primer enhanced its affinity by
      a factor of 2.3 and the maximal polymerization rate by a factor of 1.3. For the
      first time estimation was made for the contribution of replication enzymes: human
      placenta DNA polymerase and E. coli DNA polymerase I (as well as AMV reverse
      transcriptase) to a decrease in the amount of T-T dimers in DNA emerging after UV
      or gamma-irradiation. The efficiency of elongation of the d(pT)10 primer was
      shown to decrease with an increase in T-T dimers in the primer. When the d(pT)10
      primer contains about 2.6 T-T dimers per molecule, the efficiency of its
      elongation decreases by a factor of 8-18.

PMID- 8283986
TI  - [Phylogeny of amphibia based on comparison of conserved segments of the 28S rRNA
      sequence].
AB  - The sequences of two regions flanking the 5'D1 domain of 28S rRNA of 13
      vertebrate species were determined by direct rRNA sequencing through reverse
      transcriptase extension of DNA primers. Comparative treatment of these new data
      and previously reported rRNA sequences was undertaken with special reference to
      phylogenetic affinity of Amphibia by using some programs of Felsenstein's PHYLIP
      3.3 package. The results obtained suggest that Amphibia is rather a biphyletic
      than a monophyletic group, and that birds and mammals are the closest relevant.
      These data were compared with those obtained on Vertebrata by using an analogous
      comparative analysis of 18S rRNA sequences.

PMID- 8283987
TI  - [Taxonoprint DNA analysis of certain lizard species from the Lacertidae family].
AB  - It was earlier shown that electrophoretic patterns of the highly repetitive
      segments of DNA's of some animal species studied seem to have species specificity
      ("DNA taxonoprint method") [2]. In this paper the results of investigation of
      more than 20 lizard species of the Lacerta genus in comparison with
      representatives of some other genera and family are presented. It was shown that
      in taxonoprints there are one band, at least, but usually more bands common for
      all Lacerta species. Specimens of genus Podarcis have more similarity with genus
      Lacerta than genus Eremias. The representatives of Teiidae familie have no
      resemblance with family Lacertidae at all. Among Lacerta species there are 10,
      which form the separate group being very similar by most of the taxonoprints.
      This fact goes in line with hypothesis that 5 parthenogenetic species of this
      group evolve due to interspecies hybridization of another 5 bisexual species of
      this group. The other species studied have specific peculiarities in various
      taxonoprints permitting to draw some conclusions on their relations.

PMID- 8283988
TI  - [Study of the relationship of parthenogenetic forms of lizards of the species
      Lacerta and proposed parental bisexual species in comparison of DNA segments,
      considered by the polymerase chain reaction with a single primer].
AB  - Due to some suggestion [8] the parthenogenesis in vertebrates is the result of
      interspecies hybridization, and some species seem to be the main candidates
      participating in this process. DNA parts, which may be revealed using polymerase
      chain reaction in AP-RAPD modification, were compared in parthenogenetic lizards
      forms and in supposed parental species for them. As it was shown by other authors
      and confirmed by us, arbitrary primed randomly amplified DNA products are species
      specific and may be used as a molecular taxonomic criterion. It was shown that
      each parthenogenetic species studied has the patterns containing only the bands
      of one or another supposed parents and no more. This is in favour of the
      hypothesis mentioned above. Investigation of 103 10-nucleotide primers in PCR was
      done.

PMID- 8283989
TI  - [Spinal muscular atrophy in childhood. Possibilities and limits of clinical and
      molecular genetic diagnosis].
AB  - The proximal spinal muscular atrophies (SMA) are a clinically and genetically
      heterogeneous group of neuromuscular disorders which are characterized by
      selective degeneration of motor neurons in the spine and brainstem. The clinical
      features resemble other muscle diseases, the diagnostic criteria of proximal SMA
      have recently been defined by the International SMA Consortium. The
      classification of the clinical picture in different subgroups is still a focus of
      discussion. At present it seems likely that childhood onset SMA represents a
      broad spectrum of various ages of onset and different degrees of disability.
      Apart from different modes of inheritance, there is further evidence of
      heterogeneity in proximal SMA. The autosomal recessive forms represent the second
      frequent recessive disorder after cystic fibrosis, whereas autosomal dominant
      inheritance is an exception in childhood onset SMA. There are no convincing
      reports of X-linked SMA hitherto. With mapping of acute and chronic forms of
      childhood SMA to chromosome 5q11.2-13.3 diagnosis by use of DNA markers in
      affected families has become available. The current possibilities but also
      problems and limitations of genotype analysis are discussed, with special regard
      to the application of prenatal diagnosis. We report on the first experiences with
      prenatal diagnosis in 37 SMA families.

PMID- 8283990
TI  - [Aneurysmal bone cyst of the petrous bone. A rare cause of recurrent bacterial
      meningitis].
AB  - Occult malformations of the skull base are very rare disorders which cannot
      initially be diagnosed clinically. They become first symptomatic, if
      complications arise. The most frequent clinical manifestation is a recurrent
      bacterial meningitis. Based on the unique case of a presumably congenital
      aneurysmal bone cyst of the petrosal bone, which imposed clinically as hearing
      loss and recurrent bacterial meningitis, we have evaluated the extensive
      literature on this theme. Considering mostly atypical clinical findings, solely
      coronal thin-section computed tomographic scans of the skull base allow a
      reliable diagnosis. The possible risks of this investigation (necessary sedation
      up to insufflation anesthesia and the radiation exposure of the child's lens) are
      justifiable and subordinate to the diagnostic importance.

PMID- 8283992
TI  - [Congenital candida infections].
AB  - Congenital candida infection is a rare disease, although the incidence of candida
      vaginitis during pregnancy is high. We report on five cases each showing patterns
      considered typical for candida infection. The infective agent can cause
      chorioamnionitis even in the presence of intact fetal membranes. An intrauterine
      device (IUD) has been proved to be a risk factor for a congenital candida
      infection. The pathogenetic significance of contamination with candida for the
      fetus appears to depend largely on gestational age. A premature infant with a
      birth-weight less than 1500 g presented with bilateral candida endophthalmitis
      which was cured by intravenous Fluconazole therapy. Another premature infant
      weighing 800 g at birth developed a systemic candida infection. The other three
      more mature infants had milder symptoms, two of them presented with cutaneous
      candidiasis.

PMID- 8283991
TI  - [Life threatening pneumocystis carinii pneumonia in a 4-month-old boy with hyper
      IgM syndrome].
AB  - At the age of four months, a boy with a normal history and family history,
      suddenly fell ill with a life-threatening pneumocystis carinii-pneumonia.
      Surprisingly, this opportunistic infection was not brought about by a T-cell
      deficiency. However, the patient's diagnosis turned out to be the rare "Hyper-IgM
      syndrome", confirmed by: serum levels of IgM always at least normal whereas IgG,
      IgA and IgE were markedly decreased or absent; the development of neutropenia and
      occasional diarrhea. Generally, infections with pneumocystis carinii are rare in
      isolated deficiencies of immunoglobulines, but relatively frequent in primary
      "Hyper-IgM-syndrome" (approx. 12% of the cases described). The boy finally
      recovered after receiving Cotrimoxacol (20 mg/kg bw/d) in an intensive care unit.
      Now, at the age of nearly two his condition is almost good under regular
      substitution of IgG. Cotrimoxacol (4 mg/kg bw/d) is recommended to prevent
      further pneumocystis carinii infections and most of the pathogenes which
      frequently appear in neutropenias.

PMID- 8283993
TI  - [Variability of Jeune syndrome. Lung hypoplasia, renal failure and direct
      hyperbilirubinemia in a newborn infant].
AB  - Asphyxiating thoracic dysplasia (Jeune-syndrome) is an autosomal inherited
      disease which is characterized by bone dysplasia, renal and hepatic malformations
      of various expressivity. Newborns who have serious thoracic dysplasia with
      associated lung hypoplasia normally die during the neonatal period. Patients
      without signs of pulmonary defects may develop progressive renal failure due to
      an interstitial fibrosis. In addition, liver- and pancreas fibroses are found. We
      recently observed the greater variability of clinical manifestation in two
      patients with Jeune-syndrome. The first patient, a mature male newborn infant,
      presented early signs of respiratory disease and, more interestingly, had high
      serum levels of 5.1 mg/dl conjugated bilirubin at day 1; the maximal bilirubin
      concentration was 26.5 mg/dl at day 9. Additionally, he developed progressive
      renal failure (maximal serum creatinin: 2.7 mg/dl at day 13). The patient
      eventually died of respiratory failure. To our knowledge such an early onset of
      severe hepato-renal manifestation has not been observed in patients with this
      disorder. A second term newborn infant with typical radiological signs of Jeune
      syndrome and severe lung hypoplasia died within hours after birth. No hepato
      renal defects could be documented in this patient.

PMID- 8283994
TI  - [Tick bite and Lyme borreliosis. An epidemiologic study in the Erlangen area].
AB  - BACKGROUND: Lyme borreliosis is transmitted by tick bites. Approximately every
      fifth local tick (Ixodes ricinus) is infected. Transmission, therefore does not
      occur with every bite, and disease doesn't always follow infection. The goal of
      the study was to investigate the risks of infection and disease after tick bites
      in the area of Erlangen/Germany. METHODS: Between April 1989 and October 1991
      seventy-one of our out-patients (30 females, 41 males) aged 6 months to 29 years
      had a tick bite and were enrolled into the study. After the ticks had been
      removed, a blood specimen for a specific Borrelia burgdorferi antibody assay
      (IFT) was collected. An interview by phone was performed 4 weeks later and an
      appointment for a second blood collection was arranged. RESULTS: In 69 patients
      the initial titer was negative, in two patients it was 1:32. Sixty patients could
      be reached by phone, and in 43 a second blood sample was available. There was
      seroconversion detectable in 4 instances, two of whom were asymptomatic, one had
      unspecific symptoms and one developed lymphocytoma. There were no manifestations
      of late stage disease in the study population. CONCLUSION: These results confirm
      the current recommendation of the Bundesgesundheitsamt (German Federal Health
      Institute) that generally antibiotic treatment after a tick bite is not
      necessary.

PMID- 8283995
TI  - [The language of pediatric asthma patients. A study of symptom description].
AB  - BACKGROUND: Questions on asthma symptoms like "wheezing" or "whistling in the
      chest" must be easily understood by the general population. In preparation of a
      standardized German questionnaire we investigated, how children with asthma and
      their parents would describe symptoms during an asthma attack. METHODS: From June
      until December 1991, 72 children aged 13-15 years, and parents of 138 children
      aged 7-15 years with diagnosed asthma, where interviewed whilst they visited the
      outpatient department of the universities of Berlin, Leipzig, and Munich. The
      parents and children were asked to answer a questionnaire which included a list
      of adjectives and descriptions proposed to describe the child's breathing during
      an asthma attack. The items included descriptions which have been used on German
      questionnaires, others which we considered possibly useful, anc control items
      which we considered inappropriate. Parents and children were asked to rate on
      scales how much they would agree or disagree to the proposed items as possible
      descriptors. Descriptive and cluster analyses revealed those descriptions which
      received the best ratings. RESULTS: The rating was rather independent of the sex
      of the child, the respondent (child vs parent) and the severity of attacks, but
      differences between regions were observed. CONCLUSION: The verbal descriptors
      with the best rating will be used for the wording of a German questionnaire on
      asthma symptoms.

PMID- 8283996
TI  - [Intra-articular steroid therapy in treatment of chronic arthritis in childhood
      and adolescence].
AB  - OBJECTIVE: Steroids are among the most potent antirheumatic drugs, but carry
      unacceptable adverse effects during long-term systemic application. In children
      with pauciarthritis intra-articular steroids have been recommended. METHODS: We
      assessed the effect of intra-articular triamcinolone-hexacetonide in 16 joints of
      12 children and adolescents with chronic arthritis unresponsive to non-steroidal
      anti-inflammatory agents. RESULTS: All joints improved and no side effects were
      observed by clinical and roentgenographic means. After a follow-up of 12 months
      after a single injection 9 joints were without arthritis and 3 joints showed
      minimal effusion without limitation of motion. In 4 joints arthritis reappeared
      after 1, 6, 7 and 7 months. CONCLUSION: Intra-articular steroid therapy is a
      highly effective alternative in the treatment of children and adolescents with
      chronic arthritis.

PMID- 8283997
TI  - [A rapid method of HbA1c determination in a pediatric diabetic patient sample].
AB  - A new Method for HbA1c measurements (Abbott vision) was evaluated. 107 patients
      (45 F, 62 M) of a paediatric diabetes clinic participated. The mean age was 14.9
      (5.8-26.3) years, the mean duration of diabetes was 7.6 (0.1-21.1) years.
      Measurements were performed immediately after capillary blood sampling, the
      result was available within 15 min. The automated HPLC-system Diamat was used as
      a reference method, blood samples were stored at 4 degrees C and analysed within
      24 h after blood sampling. There was a close correlation between both methods (r
      = 0.96, P < 0.0001). In the lower range the results measured by Abbott Vision
      were slightly lower, whereas in the higher range the results were slightly higher
      (HbA1c (Abbott) = 1.53 + HbA1c (Diamat).0.84). The accuracy seems to be
      satisfactory for estimating metabolic control. The HbA1c-result is available
      within 15 min which means a major advantage for the management of children and
      adolescents with type I diabetes.

PMID- 8283998
TI  - [Interpretation of findings after life threatening events in infants].

PMID- 8283999
TI  - [Cough in childhood].

PMID- 8284000
TI  - Guided participation in cultural activity by toddlers and caregivers.
AB  - In this Monograph, we examine how toddlers and their caregivers from four
      cultural communities collaborate in shared activities. We focus both on
      similarities across communities in processes of guided participation--structuring
      children's participation and bridging between their understanding and that of
      their caregivers--and on differences in how guided participation occurs. We
      examine the idea that a key cultural difference entails who is responsible for
      learning--whether adults take this responsibility by structuring teaching
      situations or whether children take responsibility for learning through
      observation and through participating in adult activities with caregivers'
      support. We speculate that these two patterns relate to cultural variation in the
      segregation of children from adult activities of their community and in emphasis
      on formal schooling. The four communities of our study vary along these lines as
      well as in other ways: a Mayan Indian town in Guatemala, a middle-class urban
      group in the United States, a tribal village in India, and a middle-class urban
      neighborhood in Turkey. In each community, we visited the families of 14 toddlers
      (aged 12-24 months) for an interview that was focused on child-rearing practices,
      which included observations of caregivers helping the toddlers operate novel
      objects spontaneously during adult activities. Results are based on systematic
      analysis of patterns of communication and attention in each family in each
      community, combining the tools of ethnographic description, graphic analysis, and
      statistics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284001
TI  - Risk factors for gastrointestinal bleeding in critically ill patients. Canadian
      Critical Care Trials Group.
AB  - BACKGROUND: The efficacy of prophylaxis against stress ulcers in preventing
      gastrointestinal bleeding in critically ill patients has led to its widespread
      use. The side effects and cost of prophylaxis, however, necessitate targeting
      preventive therapy to those patients most likely to benefit. METHODS: We
      conducted a prospective multicenter cohort study in which we evaluated potential
      risk factors for stress ulceration in patients admitted to intensive care units
      and documented the occurrence of clinically important gastrointestinal bleeding
      (defined as overt bleeding in association with hemodynamic compromise or the need
      for blood transfusion). RESULTS: Of 2252 patients, 33 (1.5 percent; 95 percent
      confidence interval, 1.0 to 2.1 percent) had clinically important bleeding. Two
      strong independent risk factors for bleeding were identified: respiratory failure
      (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Of 847 patients who had
      one or both of these risk factors, 31 (3.7 percent; 95 percent confidence
      interval, 2.5 to 5.2 percent) had clinically important bleeding. Of 1405 patients
      without these risk factors, 2 (0.1 percent; 95 percent confidence interval, 0.02
      to 0.5 percent) had clinically important bleeding. The mortality rate was 48.5
      percent in the group with bleeding and 9.1 percent in the group without bleeding
      (P < 0.001). CONCLUSIONS: Few critically ill patients have clinically important
      gastrointestinal bleeding, and therefore prophylaxis against stress ulcers can be
      safely withheld from critically ill patients unless they have coagulopathy or
      require mechanical ventilation.

PMID- 8284002
TI  - A controlled study of ranitidine for the prevention of recurrent hemorrhage from
      duodenal ulcer.
AB  - BACKGROUND: Hemorrhage is the most common complication of duodenal ulcer disease,
      but there is little information about the effectiveness and safety of long-term
      maintenance therapy with histamine H2-receptor blockers. METHODS: We conducted a
      double-blind study in patients with endoscopically documented hemorrhage from
      duodenal ulcers. Patients were randomly assigned to maintenance therapy with
      ranitidine (150 mg at night) or placebo and were followed for up to three years.
      Endoscopy was performed at base line (to document that the ulcers had healed), at
      exit from the study, and when a patient had persistent ulcer symptoms unrelieved
      by antacids or had gastrointestinal bleeding. Symptomatic relapses without
      bleeding were treated with ranitidine; if the ulcer healed within eight weeks,
      the patient resumed taking the assigned study medication. RESULTS: The two groups
      were similar at entry, which usually occurred about three months after the index
      hemorrhage. After a mean follow-up of 61 weeks, 3 of the 32 patients treated with
      ranitidine had recurrent hemorrhage, as compared with 12 of the 33 given placebo
      (P < 0.05). Half the episodes of recurrent bleeding were asymptomatic. One
      patient in the ranitidine group withdrew from the study because of asymptomatic
      thrombocytopenia during the first month. CONCLUSIONS: For patients whose duodenal
      ulcers heal after severe hemorrhage, long-term maintenance therapy with
      ranitidine is safe and reduces the risk of recurrent bleeding.

PMID- 8284003
TI  - The bone density of female twins discordant for tobacco use.
AB  - BACKGROUND: Smoking is recognized as a risk factor for vertebral, forearm, and
      hip fractures. Since bone density is an important determinant of bone strength,
      we conducted a study to ascertain whether a deficit in bone density is associated
      with tobacco use and, if so, to identify the responsible mechanisms. METHODS: We
      conducted a cross-sectional study of bone density at the lumbar spine and the
      femoral neck and shaft in 41 pairs of female twins (21 monozygotic pairs), 27 to
      73 years of age (mean, 49), who were discordant for at least 5 pack-years of
      smoking (mean, 23; maximum, 64). Bone density was measured by dual-photon
      absorptiometry. The difference in bone density between the members of a pair was
      expressed as a percentage of the mean value for the pair. RESULTS: For every 10
      pack-years of smoking, the bone density of the twin who smoked more heavily was
      2.0 percent lower at the lumbar spine (P = 0.01), 0.9 percent lower at the
      femoral neck (P = 0.25), and 1.4 percent lower at the femoral shaft (P = 0.04).
      These results were not confounded by measured lifestyle factors. In the 20 pairs
      who were discordant by 20 or more pack-years (mean, 35), the (mean +/- SE) within
      pair differences in bone density at the three sites were 9.3 +/- 3.1 percent (P =
      0.008), 5.8 +/- 2.9 percent (P = 0.06), and 6.5 +/- 3.2 percent (P = 0.05),
      respectively. Smoking was associated with higher serum concentrations of follicle
      stimulating hormone (P = 0.02) and luteinizing hormone (P = 0.03) and lower serum
      concentrations of parathyroid hormone (P = 0.05). Differences in spinal bone
      density between members of a pair were associated with differences in the serum
      concentrations of parathyroid hormone (P = 0.01) and calcium (P = 0.05) and
      urinary pyridinoline excretion (P = 0.06), a marker of bone resorption.
      CONCLUSIONS: Women who smoke one pack of cigarettes each day throughout adulthood
      will, by the time of menopause, have an average deficit of 5 to 10 percent in
      bone density, which is sufficient to increase the risk of fracture.

PMID- 8284004
TI  - Recurrent spontaneous cervical-artery dissection.
AB  - BACKGROUND: Spontaneous dissection of the internal carotid and vertebral arteries
      is increasingly recognized as a cause of ischemic stroke in young people. An
      underlying arteriopathy is often suspected in the pathogenesis of such
      dissection, but the frequency of recurrent dissection is unknown. METHODS: We
      describe the long-term follow-up of 200 consecutive patients (104 women and 96
      men) with spontaneous cervical-artery dissections evaluated at the Mayo Clinic
      between 1970 and 1990. All diagnoses were confirmed by angiography. RESULTS: The
      mean age of the patients was 44.9 years (range, 16 to 76). Internal carotid
      arteries were affected in 150 patients, vertebral arteries in 37, and both in 13.
      Multivessel dissections were present in 28 percent of the patients. The mean
      follow-up was 7.4 years. Recurrent dissection occurred only in arteries not
      previously involved by dissection. A recurrent arterial dissection developed in
      16 patients (8 percent)--within a month after the initial dissection in 4
      patients (2 percent) and between 1.4 and 8.6 years later in 12 patients (a rate
      of 1 percent per year). The cumulative rate of recurrent dissection among
      patients followed for 10 years was 11.9 percent. Younger patients had a greater
      risk of recurrent dissection. CONCLUSIONS: Although dissections in multiple
      cervical vessels are common at presentation, after the first month the risk of
      recurrent dissection is only about 1 percent per year.

PMID- 8284005
TI  - Brief report: polymorphic microsatellite markers for the diagnosis of graft
      versus-host disease.

PMID- 8284006
TI  - Images in clinical medicine. Porcelain gallbladder.

PMID- 8284007
TI  - Surgical rates and operative mortality for open and laparoscopic cholecystectomy
      in Maryland.
AB  - BACKGROUND: Since 1989, laparoscopic cholecystectomy has been widely adopted as a
      treatment for gallstone disease. We analyzed the association between the
      introduction of this procedure and three variables: the rate at which
      cholecystectomy was performed in Maryland, the characteristics of patients
      undergoing cholecystectomy in routine clinical practice, and operative mortality.
      METHODS AND RESULTS: We used 1985-1992 hospital-discharge data from all 54 acute
      care hospitals in Maryland, to identify open and laparoscopic cholecystectomies,
      characteristics of patients undergoing these procedures, and deaths occurring
      during hospitalizations in which these procedures were performed. The annual rate
      of cholecystectomy, adjusted for age, rose from 1.69 per 1000 state residents in
      1987-1989 to 2.17 per 1000 residents in 1992, an increase of 28 percent (P <
      0.001). As compared with patients undergoing open cholecystectomy, patients
      undergoing laparoscopic cholecystectomy tended to be younger, less likely to have
      acute cholecystitis or a common-duct stone, and more likely to be white and have
      private health insurance or belong to a health maintenance organization (P <
      0.001). Although the operative mortality associated with laparoscopic
      cholecystectomy was less than that with open cholecystectomy (adjusted odds
      ratio, 0.22; 95 percent confidence interval, 0.13 to 0.37) and the overall
      mortality rate for all cholecystectomies declined from 0.84 percent in 1989 to
      0.56 percent in 1992, there was no significant change in the total number of
      cholecystectomy-related operative deaths because of the increase in the
      cholecystectomy rate. CONCLUSIONS: In Maryland, although the adoption of
      laparoscopic cholecystectomy has been accompanied by a 33 percent decrease in
      overall operative mortality per procedure, the total number of cholecystectomy
      related deaths has not fallen because of a 28 percent increase in the total rate
      of cholecystectomy.

PMID- 8284008
TI  - Laparoscopic general surgery.

PMID- 8284009
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 6-1994. A 31-month-old girl with fever, diarrhea, abdominal
      distention, and edema.

PMID- 8284010
TI  - Prevention of upper gastrointestinal bleeding.

PMID- 8284011
TI  - Cigarettes and the skeleton.

PMID- 8284013
TI  - Appropriateness studies.

PMID- 8284012
TI  - Appropriateness studies.

PMID- 8284014
TI  - Appropriateness studies.

PMID- 8284015
TI  - Appropriateness studies.

PMID- 8284016
TI  - Outcomes research.

PMID- 8284017
TI  - Outcomes research.

PMID- 8284018
TI  - Changing physicians' behavior.

PMID- 8284019
TI  - Uveitis and pseudojaundice during a regimen of clarithromycin, rifabutin, and
      ethambutol. MAC Study Group of the Canadian HIV Trials Network.

PMID- 8284020
TI  - Emergency kits on airplanes.

PMID- 8284021
TI  - The last well person.

PMID- 8284022
TI  - Rat and mouse proopiomelanocortin gene sequences target tissue-specific
      expression to the pituitary gland but not to the hypothalamus of transgenic mice.
AB  - The proopiomelanocortin (POMC) gene is expressed predominantly in corticotrophs
      of the pituitary anterior lobe, melanotrophs of the intermediate lobe and neurons
      of the arcuate nucleus of the hypothalamus. The different ontogeny of POMC mRNA
      as well as the complicated hormonal regulation of POMC gene expression in the
      three different cell types suggests a concerted interaction between several cis
      acting elements in the POMC gene and transcription factors located in each of the
      three cell types. To investigate cell-specific elements in the POMC gene we
      tested two different constructs in transgenic mice. The construct -4000rPOMCLacZ,
      carrying 4 kb of the rat POMC promoter fused to the Escherichia coli beta
      galactosidase gene, showed appropriate expression in melanotrophs in 50% of the
      mice analyzed. beta-Galactosidase activity was less evident in corticotrophs
      under basal environmental conditions. In brain, 7 out of 15 independently derived
      transgenic founders had ectopic expression of the transgene in different areas;
      however, none of the animals analyzed expressed beta-galactosidase in neurons of
      the arcuate nucleus. The construct HAL*, a 'tagged' 10.2-kb mouse genomic
      fragment, was more efficiently targeted to the pituitary. Using in situ
      hybridization, we detected uniform expression of HAL* in melanotrophs in 100% of
      the 6 pedigrees analyzed and transgenic mRNA levels paralleled those of the
      endogenous POMC mRNA. In corticotrophs, basal expression was low but after
      adrenalectomy HAL* mRNA levels were comparable to those of POMC. None of the 6
      pedigrees had appropriate expression of HAL* in the brain; however, 2 lines had
      ectopic expression in the dentate gyrus of the hippocampus.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8284023
TI  - Expression of vasopressin mRNA in extrahypothalamic nuclei of the homozygous
      Brattleboro rat is not modulated by testosterone.
AB  - Previous studies from this and other laboratories have shown that levels of
      vasopressin (VP) mRNA are reduced in both hypothalamic magnocellular and
      extrahypothalamic nuclei of the homozygous Brattleboro rat (HOM) when compared to
      the normal Long-Evans (LE) and heterozygous Brattleboro rats (HET). Since
      extrahypothalamic VP gene expression is dependent on testosterone (T), we
      measured plasma T in HOM, HET and LE rats. The plasma T level of the intact HOM
      rat was not significantly different from intact LE or HET rats. Manipulation of
      circulating gonadal steroids by castration and T replacement was found to
      regulate the expression of VP mRNA in the bed nucleus of the stria terminalis and
      medial amygdala of LE and HET rats, but does not appear to modify the absence of
      VP mRNA in neurons in these nuclei in the HOM rat.

PMID- 8284024
TI  - Dopamine transporter mRNA in neurons of the rat hypothalamus.
AB  - The membrane-bound dopamine transporter (DAT) protein terminates dopaminergic
      neurotransmission by rapid reaccumulation of dopamine into presynaptic nerve
      endings. The distribution of neurons expressing DAT mRNA was investigated in the
      rat hypothalamus using in situ hybridization histochemistry and oligonucleotide
      probes to sequences of rat DAT mRNA. DAT mRNA-containing cell bodies were
      demonstrated in the ventral aspect of the periventricular nucleus (A14 dopamine
      cell group), in the zona incerta (A13), in the dorsomedial part of the arcuate
      nucleus (A12), and in scattered regions of the posterior hypothalamus. There was
      no labelling in magnocellular neurons of the supraoptic or paraventricular
      nuclei, or in neurons of the ventrolateral division of the arcuate nucleus, areas
      previously shown to contain the dopamine-synthesizing enzyme tyrosine
      hydroxylase. The results suggest that hypothalamic dopamine neurons have an
      active uptake mechanism for dopamine, however, that DAT mRNA levels may be
      considerably lower than those encountered in the ventral midbrain.

PMID- 8284025
TI  - Lesions of the hippocampal efferent pathway (fimbria-fornix) do not alter
      sensitivity of adrenocorticotropin to feedback inhibition by corticosterone in
      rats.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis controls the diurnal and stress
      induced release of adrenal corticosteroids into the general blood circulation. In
      turn, corticosteroids inhibit the HPA axis under basal conditions and during
      stress through occupation of their receptors (types I and II) in the brain by
      closing a negative feedback loop. The primary site in the brain at which
      corticosteroids act to inhibit the HPA axis has not been identified. High
      concentrations of both types of receptors are found in neurons of the hippocampal
      formation, a structure which has been reported by some, but not others, to
      control activity within the HPA axis by serving as a major negative feedback
      site. In many of these past studies, blood was collected after extensive handling
      or exposure to ether, conditions which do not favor the detection of basal
      hormone concentrations. To address these controversies, we tested the feedback
      sensitivity of the anterior pituitary hormone responsible for corticosteroid
      production, adrenocorticotropin (ACTH), to corticosterone (B), the main
      corticosteroid in rats, in total fornix- and, as controls, cortex-lesioned rats.
      All rats were given vascular catheters to avoid any handling-induced differences
      in plasma B or ACTH when sampling blood. In some experiments, fornix- and cortex
      lesioned rats were adrenalectomized and given 1 of 3 doses of exogenous B
      provided in a subcutaneous pellet to ensure that plasma B was equal in different
      lesion groups. We hypothesized that if the hippocampal formation were an
      important site of B-mediated inhibition of the HPA axis, fornix-lesioned rats
      would have higher plasma B as a result of increased endogenous secretion in the
      morning or the evening compared to cortex-lesioned rats in rats with adrenal
      glands. In addition, we hypothesized that adrenalectomized fornix-lesioned rats
      given the same low to moderate levels of exogenous constant B would have higher
      basal and stress-induced ACTH than cortex-lesioned rats. Diurnal plasma B was not
      affected by fornix lesions in intact rats. Moreover, basal ACTH measured in the
      morning and the evening and stress-induced ACTH was the same in adrenalectomized
      fornix- and cortex-lesioned rats with constant exogenous B. We conclude,
      therefore, that information about occupancy of B receptors in the hippocampus
      carried by the fornix primarily subserves functions which do not directly
      regulate activity in the HPA axis.

PMID- 8284026
TI  - Effects of discrete lesions in the ventral noradrenergic ascending bundle on the
      corticotropic stress response depend on the site of the lesion and on the plasma
      levels of adrenal steroids.
AB  - Stereotaxic deletion of selected areas of the ventral noradrenergic ascending
      bundle (VNAB-X) by discrete bilateral injections of 6-hydroxydopamine (6-OHDA; 4
      micrograms in 0.2 microliter saline) was used to explore the role of brain
      catecholamines (CA) and their interaction with corticosteroid feedback in stress
      responses of the ACTH-corticosterone (CORT) axis. The stereotaxic coordinates
      used for 6-OHDA lesions and the optimization of postlesion delays were determined
      by (a) radioautographic labeling of the VNAB axons after tracer injections into
      the dorsal A2/C2, or the ventral A1/C1 medullary areas, (b) histofluorescence and
      immunocytochemical location of interrupted CA pathways versus the postlesional
      scar, and (c) postlesional noradrenaline and adrenaline concentrations in whole
      hypothalami and paraventricular nuclei (PVN) punch samples. Two sites of 6-OHDA
      lesions were selected; both led to striking falls in PVN concentrations of both
      CA. The more dorsal lesion (dVNAB-X) was the same as that of our earlier studies
      and interrupted pathways originating predominantly in the A2/C2 area; the second
      more ventral lesion (vVNAB-X) interrupted axons stemming preferentially from the
      A1/C1 area. Both VNAB lesions inhibited the ether stress-induced ACTH and CORT
      surges in rats with intact adrenals. But the blockade (overall poststress
      release, amplitude and swiftness of hormonal responses) by dVNAB-X was greater
      than by vVNAB-X. The basal ACTH level in adrenalectomized rats (ADX) was elevated
      20-fold and ether stress induced a 4-fold ACTH surge. As in sham-ADX rats, vVNAB
      X in ADX rats induced only moderate inhibition of the ACTH response versus ADX +
      sham-vVNAB-X controls. On the other hand ADX + dVNAB-X rats showed a greatly
      amplified ACTH stress response over the ADX-sham dVNAB-X controls. This
      amplification was reversed by oral CORT supplementation. The data suggest that
      the CA pathways of the VNAB participating, directly or indirectly, in the
      poststress corticotropic activation may include subsets of CA axons of different
      origins, whose functional roles in stress are modulated in opposite directions by
      the plasma corticosteroid level.

PMID- 8284027
TI  - Augmented ACTH responses to stress in adrenalectomized rats replaced with
      constant, physiological levels of corticosterone are partially normalized by
      acute increases in corticosterone.
AB  - Adrenalectomized rats replaced with constant, physiological levels of
      corticosterone via a subcutaneous pellet (Pellet) have normal basal morning ACTH
      but exhibit enhanced and prolonged ACTH responses to stress vs. sham-operated
      (Sham) rats. It has not been determined if the lack of either stress-induced or
      circadian increases in corticosterone, both of which are missing in Pellet rats,
      may account for this enhanced response. To test the extent to which stress
      associated increases in corticosterone alone can normalize stress-induced
      hypersecretion of ACTH, we approximated endogenous secretion by injecting
      additional corticosterone in Pellet rats via an indwelling subcutaneous cannula,
      5 min before hypoxia stress (10% O2). A corticosterone dose of 666 micrograms/kg
      (Pellet+B), but not 333 micrograms/kg (Pellet+Low B), produced plasma
      corticosterone levels comparable to those in Shams and normalized stress-induced
      but not post-stress plasma ACTH. Administration of the type II corticosteroid
      receptor antagonist RU 38486 30 min before corticosterone reversed this
      inhibition. We conclude that enhanced ACTH responses to stress in Pellet rats
      result in large part from lack of type II receptor-mediated feedback inhibition
      by corticosterone increases during stress, although prior circadian increases in
      corticosterone may also be required.

PMID- 8284028
TI  - Immunocytochemical localization of dopamine-releasing protein in the rat adrenal.
AB  - The mechanism by which adrenal medulla transplants to the brain of Parkinson's
      patients ameliorate the symptoms of this neurodegenerative disease is unknown. It
      has been postulated but not proven that these transplants secrete a neurotrophic
      factor(s) responsible for the activation of the dopamine (DA) neurons. DA
      releasing protein (DARP) was identified by immunocytochemistry in cells of the
      adrenal gland but not in tissues such as the liver or spleen. In the adrenal
      gland the immunopositive DARP cells were distributed both in the cortex as well
      as in the medulla. In the former, the distribution was rather uniform covering a
      broad area of the zona glomerulosa and fasciculata without positive cells in the
      zona reticularis. In the adrenal medulla the DARP signal was found in segregated
      cells forming clusters similar to the homotypic distribution of norepinephrine
      and epinephrine cells. The immunopositive cells for DARP were oval or spindle in
      shape and the staining was localized in the cytoplasm surrounding the nucleus. In
      addition, in this paper we present evidence confirming that the adrenal gland is
      the source of a protein that after immunopurification in nanogram amounts
      releases DA from corpus striatum fragments superfused in vitro. These data
      clearly demonstrate the existence of DARP in the adrenal gland and support the
      hypothesis that the effectiveness of the adrenal medulla transplants to the brain
      of Parkinson's patients is in part due to the secretion of neurotrophic factors.
      We submit that DARP is one of such factors.

PMID- 8284029
TI  - Graded hyperprolactinemia first suppresses LH pulse frequency and then pulse
      amplitude in castrated male rats.
AB  - We recently demonstrated that the ability of administered ovine prolactin (oPRL)
      to suppress postcastration LH secretion exhibited a clear dose dependency. In the
      present study, we determined whether this dose-related suppression of mean LH
      levels resulted from differential, dose-related effects of oPRL on LH pulse
      amplitude and pulse frequency. Adult male rats were orchiectomized and
      adrenalectomized, implanted with an atrial cannula and a 50% corticosterone
      pellet, and injected every 12 h with oPRL or its polyvinylpyrrolidone (PVP)
      vehicle beginning at time 0. Increasing doses of oPRL (600, 2,400 and 9,600
      micrograms/injection) suppressed mean LH titers in a dose-dependent manner at 48
      h postcastration. The mean maximal LH increments (delta LH) to two LHRH
      challenges at two doses (5 and 25 ng LHRH/100 g body weight) were unaffected by
      oPRL administration. The 600 micrograms oPRL dose significantly suppressed mean
      LH values by markedly increasing the inter-peak interval (42.6 +/- 6.7 min)
      compared with controls (26.6 +/- 0.2 min) since the pulse amplitude was
      unaffected (2.8 +/- 0.4 vs. 2.6 +/- 0.4 ng/ml, respectively). The two higher oPRL
      doses suppressed both LH pulse frequency and pulse amplitude. Hence, elevated PRL
      levels first suppress LH pulse frequency and then, at higher concentrations,
      pulse amplitude as well. Presuming that LHRH pulses result from ensemble firing
      of all or a significant proportion of the LHRH neurons projecting to the median
      eminence, the present data suggest that the neurons first affected by elevated
      PRL levels are the ones responsible for this frequency of this coordinated
      firing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284030
TI  - Altered luteinizing hormone and prolactin responses to excitatory amino acids
      during lactation.
AB  - We have used excitatory amino acids as tools to elucidate changes in hypothalamic
      function associated with lactation, focusing on the regulation of luteinizing
      hormone (LH) and prolactin secretion. In these studies, we have compared the
      responsiveness to NMA (N-methyl-D,L-aspartate), an agonist for the N-methyl-D
      aspartate (NMDA) receptor, with that of kainate, an agonist for another type of
      glutamate receptor, the kainate receptor. To address the issue of the
      permeability of the blood-brain barrier to either NMA or kainate, systemic and
      central administration of the drugs were compared. Four injections of either drug
      were administered at 10-min intervals to cycling or lactating rats suckling 8
      pups. All of these treatment significantly stimulated LH secretion in cycling
      rats. However, neither systemic injections of NMA (40 mg/kg) or kainate (2.5-3.5
      mg/kg), nor third-ventricular administration of NMA (2 micrograms/2 microliters)
      or kainate (0.2-0.3 micrograms/2 microliters) stimulated LH secretion during
      lactation. In contrast, LH responses to NMA were observed in lactating animals
      suckling 2 pups. These data demonstrate that the intensity of the suckling
      stimulus determines the degree of gonadotropin-releasing hormone (GnRH) neuronal
      inhibition during lactation. Recovery of the LH response to NMA in animals
      suckling 8 pups was not observed after treatment with RU 486 to block the effects
      of progesterone. Thus, the elevated levels of progesterone during lactation do
      not appear to play a role in inhibiting GnRH neuronal responsiveness. Removal of
      the 8-pup suckling stimulus for 24 h also did not restore the LH response to NMA.
      However, treatment with RU 486 and removal of the suckling stimulus for 24 h did
      restore LH responses to NMA, suggesting that progesterone may play a role in
      prolonging the recovery of GnRH neuronal responsiveness. The prolactin responses
      to NMA and kainate changed with the reproductive state of the animal and the site
      of administration. Central injections of either drug stimulated prolactin release
      in both cycling and lactating animals. In contrast, whereas systemic
      administration of NMA stimulated prolactin secretion in cycling animals, kainate
      had no effect. In the lactating animals, systemic administration of either drug
      inhibited prolactin secretion. Thus, the difference in the prolactin responses to
      systemic administration of the drugs may not only be due to a difference in the
      distribution of kainate and NMDA receptors but also to the steady state level of
      activity of the prolactin-releasing and -inhibiting factors which is determined
      by the reproductive state of the animal.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8284031
TI  - Modulation by glucocorticoids of growth hormone secretion in patients with
      different pituitary tumors.
AB  - The acute administration of glucocorticoids is a new stimulus of growth hormone
      (GH) secretion in man. In order to ascertain its point of action, and also the
      suitability of this new test as a diagnostic tool in GH pathological states, 33
      subjects were studied. Eight of them were normal controls, and 25 were patients
      with tumors affecting the hypothalamopituitary area. A glucocorticoid stimulus,
      dexamethasone 4 mg i.v. was administered at 0 min and GH levels (means +/- SEM,
      microgram/l) were measured during the following 5 h. In addition, GH-releasing
      hormone (GHRH) and clonidine were employed as either pituitary or hypothalamic GH
      stimuli. Dexamethasone administration to normal subjects did not alter GH levels
      in the first 2 h of the test. Afterwards, a GH peak was observed around the third
      hour, GH levels returning to basal ones thereafter. The dexamethasone-induced GH
      peak (6.7 +/- 1.5) and area under the curve (526 +/- 137) were lower than after
      GHRH (14.0 +/- 4.5 and 1,070 +/- 369, respectively). In the 14 acromegalic
      patients studied, the GHRH-induced GH net increase was similar to that observed
      in controls, while the placebo did not alter GH basal levels. An absence of
      hypothalamic control was evident because clonidine did not stimulate GH release.
      On the other hand, and contrary to normal subjects, dexamethasone strongly
      inhibited GH secretion, the values being significantly lower when calculated
      either as mean GH peak, or maximum GH increment (delta). The delta GH was -2.5 +/
      3.1 after placebo, +3.7 +/- 4.5 after clonidine, +17.0 +/- 3.3 after GHRH and 
      13.4 +/- 4.5 following dexamethasone administration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8284032
TI  - Localization of a laminin-binding protein in brain.
AB  - A 110,000 mol.wt laminin-binding protein from newborn mouse brain recognizes a
      neurite promoting laminin A chain site and is related to the beta-amyloid
      precursor protein. In the present study, we examined the expression of 110,000
      mol.wt laminin-binding protein in brains of adult mice, rats, and non-human
      primates. Essentially identical immunoreactivities were observed across species
      with distinct staining of cortical pyramidal neurons with apical dendrites,
      cerebellar basket cell axons, hippocampal mossy fibers, and fine labeling of
      processes throughout the brain. Colocalization of immunoreactivities to 110,000
      mol.wt laminin-binding protein and to laminin in neurons of the adult rat brain
      was observed. Electron microscopy demonstrated that 110,000 mol.wt laminin
      binding protein-like immunoreactivity is intracellular and is possibly associated
      with the neuronal cytoskeleton. Western blot analysis revealed that anti-110,000
      mol.wt laminin-binding protein also recognizes a 140,000 mol.wt protein in the
      pellet, in addition to the 110,000 mol.wt protein in the Triton soluble extract.
      Antibody fractions specific to the two reactive protein species (110,000 mol.wt
      and 140,000 mol.wt) exhibited cross-reactivity on immunoblots and revealed
      similar immunohistochemical staining in adult brain. Results suggest a
      significant interaction between laminin-like molecules and 110,000 mol.wt laminin
      binding protein-like molecules in normal brain function, in response to CNS
      injury and possibly in the pathogenesis of Alzheimer's disease.

PMID- 8284033
TI  - Cellular localization of messenger RNA for beta-1 and beta-2 adrenergic receptors
      in rat brain: an in situ hybridization study.
AB  - Selective, 35S-labeled, oligonucleotide probes were designed from sequences of
      the rat beta-1 and beta-2 adrenoceptor messenger RNAs for use in situ
      hybridization experiments on sections of unfixed rat brain and spinal cord. After
      hybridized sections were exposed to film or dipped in autoradiographic emulsion,
      specific and selective labeling patterns characteristic for each receptor
      messenger RNA and region of the central nervous system were observed. For
      example, labeling for beta-1 messenger RNA was found in the anterior olfactory
      nucleus, cerebral cortex, lateral intermediate septal nucleus, reticular thalamic
      nucleus, oculomotor complex, vestibular nuclei, deep cerebellar nuclei, trapezoid
      nucleus, abducens nucleus, ventrolateral pontine and medullary reticular
      formations, the intermediate gray matter of the spinal cord and in the pineal
      gland, while beta-2 messenger RNA labeling was strongest in the olfactory bulb,
      piriform cortex, hippocampal formation, thalamic intralaminar nuclei and
      cerebellar cortex. In some of these regions the beta-1 labeling seemed mainly
      confined to the cell nucleus. Whether or not this apparently nuclear labeling is
      specific, i.e. indicates synthesis of beta-1 receptor, remains to be established.
      However, all labeling patterns described disappeared when excess unlabeled probes
      were added to their respective radiolabeled probes or when sense probes were
      employed. Since the in situ method labels only cell bodies that produce the
      messenger RNA for these two beta receptor subtypes, a comparison between these
      maps and those of past autoradiographic studies mapping the location of central
      beta receptors using drugs as radioligands may produce further insights regarding
      the pre- and postsynaptic localization of these receptors in the various parts of
      the central nervous system circuitry.

PMID- 8284034
TI  - Co-expression of four muscarinic receptor genes by the intrinsic neurons of the
      rat and guinea-pig heart.
AB  - Expression of the messenger RNAs encoding the five different muscarinic
      acetylcholine receptor subtypes was examined in intracardiac neurons from the rat
      and guinea-pig heart by in situ hybridization techniques. Newborn guinea-pig
      intracardiac neurons were studied in dissociated cell culture preparations
      employing both 35S- and digoxigenin-labelled oligonucleotide probes specific for
      the m1, m2, m3, m4 or m5 muscarinic receptor messenger RNAs. When 35S-tailed
      oligonucleotides were used, all intracardiac neurons in culture were found to
      express m1, m2, m3 and m4, but not m5 messenger RNAs. However after hybridization
      with digoxigenin-tailed probes, only m1 and m2 transcripts were detected. This
      may reflect differences in the sensitivity of the two techniques. Further to
      these experiments, intracardiac ganglia in sections of adult rat heart were
      studied employing m1-, m2-, m3- or m4-specific, 35S-labelled oligonucleotides,
      and again, all intracardiac neurons expressed messenger RNA for each of these
      four muscarinic receptor subtypes. Atrial myocytes in culture were only labelled
      by [35S]- and digoxigenin-tailed m2 oligonucleotides. No other heart cell type
      seen expressed messenger RNA for any of the muscarinic receptors. The expression
      of four different muscarinic receptor transcripts by intrinsic neurons of the
      heart provides the molecular basis for the diverse muscarinic actions observed in
      these and other autonomic ganglia.

PMID- 8284035
TI  - Processing of photic information within the intergeniculate leaflet of the
      lateral geniculate body: assessed by neuropeptide Y immunoreactivity in the
      suprachiasmatic nucleus of rats.
AB  - Entrainment of the circadian pacemaker in the suprachiasmatic nucleus is
      accomplished by two neural pathways, the retinohypothalamic and
      geniculohypothalamic tracts. The geniculohypothalamic tract, which originates
      from the intergeniculate leaflet and a portion of the ventral lateral geniculate
      nucleus, is composed of fibers immunoreactive to neuropeptide Y. To assess the
      processing of photic information by the geniculohypothalamic tract, neuropeptide
      Y immunoreactivity in the suprachiasmatic nucleus of rats kept under various
      external lighting conditions was determined by enzyme immunoassay of micropunched
      tissues. Neuropeptide Y levels in the suprachiasmatic nucleus steadily increased
      when rats were exposed to continuous light and reached a peak in 2 h before
      returning to basal level. The amount of increase did not depend on intensity and
      duration of light exposure. A light pulse as short as 5 min elicited a similar
      rise in neuropeptide Y, indicating that the response is due to the sudden
      transition from dark to light. This response, however, was only observed when the
      dark to light transition occurred at circadian time 0 (subjective dawn) of the
      pacemaker. A light pulse at circadian time 0, which effectively induces the
      increase in neuropeptide Y level, does not significantly shift the phase of the
      circadian rhythm. This observation indicates that the photic pathway utilizing
      neuropeptide Y may be functional only when the endogenous circadian rhythm is
      synchronized to external light and dark cycles. Administration of an excitatory
      amino acid antagonist (MK-801) blocked the increase of neuropeptide Y by light,
      while an agonist (N-methyl-D-aspartate) induced similar facilitatory effects to
      that of light on the neuropeptide Y level in the rat suprachiasmatic nucleus.
      These results suggest that the geniculohypothalamic tract processes photic
      information so as to facilitate distinction of the transition between light and
      darkness that occurs either at subjective dawn or dusk.

PMID- 8284036
TI  - Differential responses of identified rat hypothalamic paraventricular neurons to
      suprachiasmatic nucleus stimulation.
AB  - The suprachiasmatic nucleus in the anterior hypothalamus contains a circadian
      oscillator that is responsible for 24-h rhythms in several behavioral, endocrine
      and autonomic processes. Efferent suprachiasmatic projections are likely to
      transmit rhythmic information to brain nuclei controlling these functions. The
      hypothalamic paraventricular nucleus is considered to be a target of the
      suprachiasmatic nucleus due to its important role in autonomic and endocrine
      regulation. The present study applied extracellular electrophysiological
      techniques to intact animals to look for a possible interaction between
      suprachiasmatic nucleus efferents and identified neurons in the hypothalamic
      paraventricular nucleus. Results showed that electrical stimulation of the
      suprachiasmatic nucleus induced an increase in the excitability of 87% of
      paraventricular neurons that project to the median eminence and are situated in
      the medial and dorsal parvocellular subnucleus; neurons with similar projections
      but located in the periventricular subnucleus displayed a reduction in firing
      rate following suprachiasmatic stimulation. Electrical activation of the
      suprachiasmatic nucleus provoked a decrease in excitability in 75% of
      paraventricular neurons in the posterior magnocellular subnucleus that send axons
      to the posterior pituitary and in 85% of paraventricular neurons, located in the
      medial parvocellular subnucleus, that project to the dorsal vagus complex in the
      brainstem. The data imply that functional and selective neural connections exist
      between suprachiasmatic nucleus efferents and specific cell groups within the
      hypothalamic paraventricular nucleus. These projections would be able to convey
      rhythmic information to certain endocrine and autonomic functions. The anatomical
      and neurochemical characteristics of the underlying pathways remain to be
      determined.

PMID- 8284037
TI  - Neuronal subtypes and anatomic asymmetry: changes in neuronal number and cell
      packing density.
AB  - The combined volume of an asymmetric cytoarchitectonic area is smaller than that
      of symmetric homologs. Asymmetry reflects fewer numbers of neurons in the smaller
      of the two sides. In this study we examined two types of neurons to check whether
      lateral differences in neuronal numbers affect different types of neurons
      comparably in the neocortex of the rat. As with overall neuronal numbers, both
      parvalbumin-immunoreactive (mostly long projection) neurons, and vasoactive
      intestinal peptide-immunoreactive interneurons increase in number in the larger
      of the two sides. Moreover, the concentration of parvalbumin- but not vasoactive
      intestinal peptide-immunoreactive neurons also increases on the larger side.
      Thus, there may be qualitative as well as quantitative differences in the
      connectivity of the larger side of an asymmetric architectonic region.

PMID- 8284038
TI  - Organization of cortical afferent input to orbitofrontal areas in the rhesus
      monkey.
AB  - Odorant signal processing takes place in a diverse group of primary olfactory
      areas which receive direct input from the olfactory bulb. Orbitofrontal cortices
      participate in olfactory functions, but the pathways through which they receive
      olfactory or other input have not been clearly defined. The retrograde tracers
      horseradish peroxidase and fluorescent dyes were injected in orbital cortices to
      study their afferent cortical connections. Labeled neurons in primary olfactory
      areas (prepiriform cortex, anterior olfactory nucleus and olfactory tubercle)
      were directed mainly to a posterior orbitofrontal region and to a lesser extent
      the neighboring caudal part of area 13. There was no evidence of direct
      projections from primary olfactory areas to the rostral parts of area 13, or to
      areas 12 or 11. Most labeled neurons in primary olfactory areas were directed to
      agranular cortices, fewer projected to dysgranular areas, and there was no
      evidence that any reached granular cortices. The areas which received the most
      robust olfactory projections showed the lowest degree of laminar organization
      among prefrontal cortices. Early processing in the olfactory system thus takes
      place in areas which differ sharply on structural grounds from "early" eulaminate
      post-Rolandic sensory cortices. In addition to olfactory cortical projections,
      numerous labeled neurons in transitional (limbic) cortices were directed to
      orbital areas, and fewer but still substantial numbers of afferent neurons were
      found in eulaminate cortices. Unlike post-Rolandic unimodal sensory areas, which
      seems to be committed to the processing of input from one sensory modality via
      sequential and/or parallel pathways, caudal orbital areas received highly
      distributed input from primary olfactory areas, and in addition, from gustatory,
      visual, auditory and somatosensory areas. The structural and connectional
      features of olfactory recipient orbital cortices thus differ markedly from those
      observed in other sensory association areas and suggest a mode of processing
      adapted early in cortical evolution.

PMID- 8284039
TI  - Dynamics of orientation tuning in the cat striate cortex neurons.
AB  - Dynamics of orientation tuning was studied by a flashing light bar in 233 single
      units of cat primary visual cortex. Orientation tuning was plotted by the
      criterion of spike number in successive fragments of responses with a step of 10
      or 20 ms. Preferred orientation and the width of orientation tuning were measured
      for each of such curves. It was found that successive dynamic change of preferred
      orientation during response was typical for 63% of units under study, while such
      change of orientation tuning width was typical for 93%. Neurons with or without
      shift in preferred orientation differed in their response characteristics:
      latency and duration of discharge, its frequency and response rise time, as well
      as quality of orientation tuning. Possible functional significance of two groups
      of cortical units, "scanners" (with systematic preferred orientation shift) and
      "timers" (without it), is discussed in accordance with the idea of spatiotemporal
      orientation coding in the primary visual cortex.

PMID- 8284040
TI  - Distribution of seven major neurotransmitter receptors in the striate cortex of
      the New World monkey Callithrix jacchus.
AB  - The distribution of seven different binding sites for the transmitters L
      glutamate (L-glutamate binding sites and N-methyl-D-aspartate receptor), GABA
      (GABAA receptor), noradrenaline (alpha 1 receptor), acetylcholine (muscarinic M1
      and M2 receptors) and serotonin (5-hydroxytryptamine1 receptor) are analysed in
      the primary visual cortex (area 17) of the common marmoset, Callithrix jacchus,
      using quantitative autoradiography. All binding sites show a well-defined laminar
      pattern, which changes sharply at the cytoarchitectonic border to area 18. The
      quantitative data show that the distribution of different receptors is relatively
      invariant across the cortical layers. Almost all receptors show a maximum in
      supragranular layers, low densities in layers IVA/IVB and a second maximum in
      layer IVC. Statistical analysis of these similarities in laminar distribution
      patterns of different receptors (co-distribution) reveals, as in other brain
      regions and species, that L-glutamate binding sites are co-distributed with N
      methyl-D-aspartate, GABAA, and muscarinic M1 and M2 receptors. This may reflect
      the structural basis of a possible interaction between these receptors and their
      respective transmitters on the level of single cortical layers. Further co
      distributions are found between N-methyl-D-aspartate, GABAA and M1, as well as
      between alpha 1 and M1 and finally between M1 and M2 receptors. Since not all
      receptors are co-distributed, the similarities in laminar patterns reveal
      specific aspects of the neurochemical organization of the cortex when receptors
      of different transmitter systems are analysed in the same brain.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8284041
TI  - Persistent muscarinic excitation in guinea-pig olfactory cortex neurons:
      involvement of a slow post-stimulus afterdepolarizing current.
AB  - The persistent excitatory effects of the muscarinic agonist oxotremorine-M were
      investigated in guinea-pig olfactory cortex neurons in vitro (28-30 degrees C)
      using a single-microelectrode current-clamp/voltage-clamp technique. In 40% of
      recorded cells (type 1), bath-application of oxotremorine-M (2-10 microM; 1-2
      min) induced a strong membrane depolarization, an increase in input resistance
      and a sustained neuronal discharge lasting over 30 min following agonist washout.
      A large depolarizing stimulus applied during the action of oxotremorine-M, evoked
      a slow post-stimulus afterdepolarization (approximately 10-15 mV) lasting
      approximately 30 s. Injection of steady negative current at the peak of this
      response produced a slow repolarization of the membrane potential (half-time
      approximately 0.6 min) towards a plateau level ("hyperpolarization recovery");
      these effects of oxotremorine-M were slowly reversed on washout or by application
      of atropine (1 microM). In a second population of neurons (type 2; 39% of total),
      oxotremorine-M produced a large depolarization, a resistance increase and
      repetitive firing that did not persist after agonist washout; these neurons
      failed to generate a prominent slow afterdepolarization on stimulation, and
      showed no hyperpolarization recovery effect. Their resting membrane properties
      were not significantly different from those of type 1 cells. The remaining
      proportion of cells (type 3) elicited little or no muscarinic response to
      oxotremorine-M and no slow afterdepolarization; these cells showed
      characteristics spike fractionation (pre-potentials) during an evoked train of
      action potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284042
TI  - GABAergic control of odour-induced activity in the frog olfactory bulb: possible
      GABAergic modulation of granule cell inhibitory action.
AB  - In the olfactory bulb, the activity of the output neurons, the mitral cells, is
      under inhibitory control exerted by GABAergic interneurons, the granule cells.
      Although the mechanisms of this inhibition are well known from in vitro studies,
      its physiological role in controlling mitral cell activity in response to odours
      has never been investigated. This study planned to improve understanding of the
      involvement of granule cells. To do so, GABAA-synaptic mechanisms were altered
      using GABAA antagonists in order to observe the consequences on mitral cell
      electrophysiological responses to odours, delivered over a wide concentration
      range. Due to the laminar organization of bulbar cell populations, the
      antagonists picrotoxin or bicuculline were injected into the bulbar ventricle in
      order to block granule cell inhibitory action at first. Surprisingly, the early
      consequence of the antagonist injection was a decrease in cell responsivity:
      response spike frequencies were lowered while thresholds were occasionally
      shifted toward higher concentrations. This initial depressive effect was followed
      by a recovery of control excitability and, later, by an increase in excitability:
      spike bursts became more sustained in frequency and in duration. At the same
      time, in most of the cells studied, spontaneous activity became bursting. The
      early depressive effect of GABAA antagonists is discussed in terms of an
      enhancement of the inhibitory influence of granule cells on mitral cells. This
      might reflect a blocking action of the antagonists at the level of GABAergic
      synapses located on granule cells themselves. The late effect, an increase in
      excitability, is explained as the consequence of the alteration of the
      functioning of dendrodendritic synapses between granule and mitral cells leading
      to a disinhibition of the latter. The comparison of the present findings with
      others obtained when antagonists were applied on to glomerular layers led us to
      infer that granule cell inhibition would be devoted to limiting mitral cell
      responses in frequency and in duration rather than to adjusting their response
      threshold. The chronology of the effects observed strongly supports the fact
      that, following the intraventricular injection, the antagonists acted primarily
      in the deep layers of the bulb. Nevertheless, due to free diffusion starting from
      the injection site, the possibility that drugs act later in the glomerular layer
      can not be rejected. It can be concluded that, in addition to its extensive
      involvement through intrinsic interneurons, GABA might also control the strength
      of the inhibition exerted by granule cells on mitral cells via centrifugal
      fibres.

PMID- 8284043
TI  - CGS-19755 is neuroprotective during repetitive ischemia: this effect is
      significantly enhanced when combined with hypothermia.
AB  - In small animals the damaging effects of repetitive ischemia are more severe than
      a single insult of similar duration. Prolonged release of glutamate may correlate
      with the degree of damage. We report the protective effects of CGS-19755 (an N
      methyl-D-aspartate receptor blocker), hypothermia or CGS-19755 in combination
      with mild hypothermia, in a gerbil model of repetitive ischemia. We used 3 min of
      forebrain ischemia and repeated it for a total of three times as 1-h intervals.
      Damage was assessed seven days after the insult. In the group where only CGS
      19755 was used, significant neuronal protection was evident in the hippocampus
      (CA1 and CA3), striatum, and medial geniculate nucleus. With hypothermia
      significantly less damage was seen in the cerebral cortex, hippocampus (CA1 and
      CA4), and substantia nigra reticulata. When CGS-19755 was combined with mild
      hypothermia the effects of repetitive ischemia were completely abolished in all
      but one gerbil. Compared to hypothermia alone, significant protection was seen in
      the cerebral cortex, hippocampus (sibiculum, CA1 and CA4), striatum, medial
      geniculate nucleus, thalamus, and substantia nigra reticulata. The use of N
      methyl-D-aspartate receptor blockers may protect the brain in repetitive
      ischemia. Combination with hypothermia may further enhance this protection.

PMID- 8284044
TI  - Temporal profile of heat shock protein 70 synthesis in ischemic tolerance induced
      by preconditioning ischemia in rat hippocampus.
AB  - We investigated the temporal profile of heat shock protein 70 induction in the
      rat hippocampus using immunohistochemistry to clarify the mechanism of ischemic
      tolerance following preconditioning with sublethal ischemia. Although a 6-min
      period of forebrain ischemia produced severe neuronal damage to the hippocampal
      CA1 subfield, preconditioning with 3 min of ischemia followed by three days of
      reperfusion protected against the CA1 neuronal damage after 6 min of ischemia.
      Immunohistochemical staining against heat shock protein 70 showed that the
      protein is induced in CA1 pyramidal cells one, three and seven days after 3 min
      of ischemia, the immunostaining being most intense after three days. Heat shock
      protein synthesis was observed in CA1, CA3 and dentate hilar neurons one and
      three days after 6 min of ischemia, both with and without preconditioning. In
      addition, the heat shock protein was stained in the CA1 2 h and seven days after
      6 min of ischemia with preconditioning, but the intensity of staining was
      relatively weak at these time points. The results suggest that stress response
      induced by sublethal ischemia protects against ischemic neuronal damage, and that
      the induced stress response, including heat shock protein 70 synthesis during and
      immediately after the second ischemic episode, is correlated with the protection
      because late induction of the heat shock protein did not prevent neuronal death.

PMID- 8284045
TI  - Microglial responses to physiological change: osmotic stress elevates DNA
      synthesis of neurohypophyseal microglia.
AB  - We were interested to discover whether microglia could play a role in the
      remodelling of the adult CNS or participate in adaptations to physiological
      rather than pathological changes. We have studied microglia in the
      neurohypophysis of adult mice since microglia normally interact with neurons in
      this tissue and the biochemical and anatomical consequences of osmotic stress on
      the neurohypophysis are well known. In this study, we have examined microglial
      immuno-phenotype and numbers synthesizing DNA in the neurohypophysis of adult
      mice to establish whether these cells respond to progressive osmotic stress.
      Neurohypophyseal F4/80+ microglia underwent a large synchronous burst of DNA
      synthesis 48 h after initiation of osmotic stress (drinking 2.5% saline). The
      labelling index (percentage of F4/80+ cells labelled by [3H]thymidine) 1 h after
      injection the isotope rose to 17% from a control value of less than 1%. On the
      third day of treatment the labelling index had returned to control levels. In
      contrast, non-microglia cells in the neurohypophysis and microglial cells
      elsewhere in the brain did not show this response. The increase in DNA synthesis
      was not accompanied by signs of microglia activation commonly observed in
      inflammatory models. They did not acquire an "activated" or "hypertrophic"
      morphology, nor was their staining with a panel of antibodies greatly altered. A
      small up-regulation of CD45 expression was the only phenotypic change detected.
      Thus, neurohypophyseal microglia respond to increased neurosecretory activity
      during the adaptation to osmotic stress in a distinctive way which differs from
      microglia reactions to inflammatory stimuli elsewhere in the CNS.

PMID- 8284046
TI  - Anatomical and functional consequences of induced rejection of intracranial
      retinal transplants.
AB  - Retinae from embryonic rats transplanted over the midbrain of newborn host rats
      establish connections with visual centres of the host brain, which mediate a
      pupilloconstrictor response in the host eye when the transplant is stimulated by
      light. The changes in the size of the host pupil can be measured accurately with
      a pupillometry system. We have taken advantage of the additional observation that
      while grafts between rat strains, as between Long Evans and Sprague-Dawley
      strains, may survive indefinitely, they can be induced to reject by skin grafting
      from the strain providing the donor retinal tissue. Combining pupillometry with
      skin grafting provides a useful way of examining correlated anatomical and
      behavioural changes associated with graft rejection from its earliest stage to
      the point of overt destruction. Even within three days of skin grafting, the
      amplitude and speed of constriction as well as the response latency all showed
      significant enhancement from normal, and this was sustained for a further week or
      more. Response deterioration followed during the second week post-skin grafting,
      but the exact timing varied considerably among animals. Anatomical observations
      of the process of retinal rejection showed the first invasion of lymphocytes to
      occur between days 5 and 7 and total degeneration of the retinal transplant and
      its projections to occur by two to three weeks post-skin grafting. The
      lymphocytic infiltration was preceded by upregulation of microglia, which
      expressed both class I and II major histocompatibility antigens and by activation
      of astrocytes identified by their expression of glial fibrillary acidic protein.
      Within the target region of retinal transplant axons, major histocompatibility
      antigen expression and astrocytic responses preceded degeneration of transplant
      derived axons (demonstrated by the Fink-Heimer stain) and there was no evidence
      for any lymphocytic lymphocytic infiltration during transplant rejection. These
      observations show that the earliest stages of microglial activation are
      accompanied by an enhancement of response parameters, but that the functional
      failure finally occurs only at an advanced stage of graft destruction. The
      absence of lymphocytic infiltration into areas receiving terminals from axons of
      transplant origin, even though these contain significant numbers of reactive
      microglia, suggests that the terminal axonal processes are not a primary target
      for the immune response.

PMID- 8284047
TI  - Synaptic relationships between GABA-immunoreactive boutons and primary afferent
      terminals in the rat cuneate nucleus.
AB  - The present study examined the synaptic relation between the primary afferent
      terminals and intrinsic neuronal elements in the rat cuneate nucleus. For this
      purpose, experimental degeneration after multiple cervicothoracic dorsal
      rhizotomies or anterograde transport of wheatgerm agglutinin conjugated to
      horseradish peroxidase were used to identify the primary afferent terminals,
      while immunogold postembedding staining was employed to identify the GABA
      immunoreactive boutons. The combined procedure allowed us to demonstrate a direct
      synaptic relationship between the primary afferent terminals and GABA
      immunoreactive boutons. At least two types of synaptic relation were observed
      between the primary afferent terminals, identified by their degenerating features
      or labeled by wheatgerm agglutinin conjugated to horseradish peroxidase, and the
      immunogold-labeled GABA-immunoreactive boutons (i) a GABA-immunoreactive bouton
      making a simple presynaptic contact with the primary afferent terminal; and (ii)
      a synaptic glomerular complex in which the centrally located primary afferent
      terminal was postsynaptic to a GABA-immunoreactive bouton and presynaptic to
      dendrites closely associated with it; both terminals were sometimes presynaptic
      to a common dendrite. It is speculated from this study that the incoming impulses
      from the forelimb area are modulated by the GABA-immunoreactive boutons in the
      cuneate nucleus of the rat.

PMID- 8284048
TI  - Modulation of the locomotor response to amphetamine by corticosterone.
AB  - In the present experiments, we investigated the influence of chronic
      modifications of circulating levels of corticosterone on the locomotor response
      to amphetamine. Different groups of rats were adrenalectomized and implanted
      subcutaneously with pellets releasing different amounts of corticosterone (0-200
      mg). A wide range of corticosterone concentrations was reached in order to
      saturate selectively either the type I (mineralocorticoid) or the type II
      (glucocorticoid) corticosteroid receptors. The locomotor response to d
      amphetamine (1.5 mg/kg) was studied 10-14 days later. We found that adrenalectomy
      reduced the response to d-amphetamine by 33% and that a normal response was
      restored with pellets releasing physiological concentrations of corticosterone
      (50-mg pellets), and was potentiated in animals with pellets releasing high
      amounts of corticosterone mimicking chronic stress situations (200-mg pellets).
      The correlation between plasma corticosterone concentration, locomotor activity
      following d-amphetamine and thymus weight, which is a reliable indicator of
      glucocorticoid action, shows that the influence of the locomotor response to d
      amphetamine administration is likely to be mediated via a type II receptor. Since
      the locomotor activating effect of peripheral administration of d-amphetamine has
      been shown to depend on the integrity of the dopaminergic innervation of the
      nucleus accumbens, the effect of d-amphetamine at different doses (0, 1, 3, 10
      micrograms/microliter) injected directly into the nucleus accumbens was studied.
      The results demonstrated that removing the circulating corticosterone induced a
      similar decrease of the locomotor activity elicited by d-amphetamine injection in
      the nucleus accumbens. This response was restored in animals with the 50- and 200
      mg pellets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284049
TI  - Chemical casualty decontamination.

PMID- 8284050
TI  - The Winchester Accord: the Confederacy and the humane treatment of captive
      medical officers.
AB  - Civil war prisoners of war fared badly. But there was one extraordinary wartime
      development that promoted the humane treatment of captive enemy soldiers.
      Beginning in June 1862, Union and Confederate authorities regarded medical
      officers as non-combatants. Largely attributable to the initiative of Hunter
      Holmes McGuire, Stonewall Jackson's medical director, this principle, set down at
      Winchester, Virginia, eased the horrors of the Civil War battlefield by allowing
      medical personnel to continue their lifesaving work unmolested.

PMID- 8284051
TI  - Marketing and utilization of the Active Duty Dependent's Dental Insurance Plan.
AB  - Based on a random, representative sample of 2,733 officer and 7,938 enlisted Army
      enrollees in the Active Duty Dependent's Dental Insurance Plan (ADDDIP), we found
      that soldiers turned to many sources to learn about the plan and that oral
      sources were consulted more commonly than written sources. More than 40% of Army
      enrollees have never used the plan. Officer dependents have used the ADDDIP to a
      fuller extent than enlisted dependents. Over half of Army enrollees felt that
      program enrollment should be renewed automatically. The best-liked features of
      the ADDDIP included good cost value, known services covered, and access to a
      single family dentist.

PMID- 8284052
TI  - The relationship between sporting activity and smoking habits in young adults.
AB  - The authors investigated the relationship between sporting activity and smoking
      habits in young Italian men. One thousand, one hundred fifty-three men, age 20
      years, completed a self-administered questionnaire on their smoking habits and
      sporting activity patterns. Five hundred sixty subjects (53%) were found to be
      smokers, with a high prevalence of heavy smokers (33.6%). Four hundred sixty-four
      (44%) of the examined subjects were sportsmen. In the group of young men not
      engaged in sports, the rate of smokers was significantly higher. Non-sportsmen
      started smoking earlier than sportsmen, and the prevalence of heavy smokers was
      significantly higher in the non-sportsmen group than in the sportsmen group.
      Finally, the young men not engaged in sports were more likely to be habitual
      smoke inhalers than sportsmen. These results suggest that sporting activity may
      indirectly influence smoking habits.

PMID- 8284053
TI  - An epidemiologic method for assessing the effectiveness of hearing conservation
      programs using audiometric data.
AB  - A hearing conservation program (HCP) must include audiometric monitoring. In
      keeping with this requirement, enormous bodies of audiometric data have been
      accumulated. However, only a limited number of methods are available for using
      audiometric data to assess HCP effectiveness. This study illustrates an
      epidemiologic method. The risk of developing hearing loss (measured by the
      standard threshold shift) was compared between study and reference populations
      using the risk ratio. The study population had an increased risk of nearly 3
      fold. Epidemiologic risk comparison methods, using reference populations, offer
      an alternative to current methods for HCP evaluation using audiometric data.

PMID- 8284054
TI  - Clients, problems, and diagnoses in a military community mental health clinic: a
      20-month study.
AB  - A descriptive epidemiologic study was performed using intake data from an Army
      community mental health clinic. This clinic was on a U.S. Army non-training post;
      data were collected over a 20-month period. Two diagnoses, occupational problem
      and phase of life or other life circumstance problem, were utilized by clinicians
      in 51% of all cases. Axis I diagnoses were found in 21% of the cases and
      medication was prescribed in 7%. Women were over-represented relative to men. We
      concluded that the patterns of diagnoses reflected the demand characteristics of
      the military environment. One implication of this study is that psychiatric care
      must be examined in the context of the community and not just as an
      administrative or economic system.

PMID- 8284055
TI  - Differences in self- and supervisor-referrals to a military mental health clinic.
AB  - Supervisor- and self-referrals for outpatient mental health care were studied to
      determine demographic and clinical differences. Supervisor-referrals (n = 730)
      were younger, reported fewer problems, and received less severe diagnoses than
      the self-referrals. Self-referrals (n = 1,103) received more depressive and
      anxiety diagnoses and more medications. They were also more afraid to ask for
      help, were more likely to not know where to go for help, say that "no one cares,"
      fear disclosure, and to fear the outcome than the supervisor-referrals.
      Supervisor-referral may permit earlier intervention into client problems, but the
      nature of the social contingencies contributing to referral requires more
      research.

PMID- 8284056
TI  - Open half-pin insertion for distal radial fractures.
AB  - Twenty-two patients with unstable distal radial fractures were treated with
      external fixation using the open technique for half-pin insertion. Of the final
      study group of 19 patients, 7 (37%) demonstrated early pin-tract drainage, which
      resolved within 2 weeks after insertion. No pin loosening, pin change, pin
      breakage, infection, dorsal sensory nerve entrapment or irritation, tendon
      injury, or additional radial fracture occurred. Wrist range of motion in
      flexion/extension was 51/47 degrees, and the grip strength ratio (injured versus
      non-injured side) was approximately 61% on follow-up (average, 8 months). The
      open technique has proved efficacious in reducing complications associated with
      external fixation.

PMID- 8284057
TI  - Gastrointestinal endoscopy support for the carrier battle group.
AB  - During workups and subsequent 1989-1990 Mediterranean deployment, the USS
      Forrestal performed 27 endoscopic procedures at sea. The procedures, indications,
      and findings are presented, and the usefulness of expanded capabilities of
      delivering medical care to the deployed battle group is discussed. Upgrading the
      quality of the patient care as well as cost savings for such care is also
      presented.

PMID- 8284058
TI  - Serum endotoxin, tumor necrosis factor, and interleukin-6 response to total hip
      arthroplasty.
AB  - The purpose of this study was to determine if endotoxin, tumor necrosis factor
      (TNF), and interleukin 6 (IL-6) increased in patients during or after total hip
      arthroplasty. Endotoxin is absorbed from the gut lumen and stimulates macrophages
      to make TNF. TNF is one of the stimuli for the increased production of IL-6. All
      three entities cause fever. If an increase takes place in any of the three, it
      could contribute to the commonly observed postop fever in total hip patients.
      Five serum samples were obtained from 12 patients: preoperatively; after the
      acetabular component was seated intraoperatively; in the recovery room; day 1
      postoperatively; and day 3 postoperatively. IL-6 and TNF were measured using
      monoclonal antibody tests and endotoxin was measured with a chromogenic limulus
      amoebocyte lysate assay. A statistically significant increase in all three
      parameters was demonstrated. Endotoxin peaked intraoperatively or in the recovery
      room, TNF tended to peak in the recovery room, and the peak in IL-6 was more
      variable. Ten patients had a concomitant postoperative fever.

PMID- 8284059
TI  - Psychiatric managed care at a rural MEDDAC.
AB  - Mental health costs at General Leonard Wood Army Community Hospital (GLWACH) have
      risen every year. In 1990, $2.7 million had been spent on CHAMPUS mental health
      costs, 58% of the entire CHAMPUS costs for the hospital's catchment area. Gateway
      to Care, a plan of coordinated managed care conceived by Health Services Command,
      was initiated at GLWACH to give the commander and providers more flexibility to
      control costs and improve access to care. Five major changes were made under
      GLWACH's mental health coordinated care project. In the first full year of the
      project, CHAMPUS net costs were reduced to $1.4 million while more comprehensive
      care was provided to beneficiaries. Cost reduction came primarily from
      dramatically increasing the size and scope of outpatient care to reduce inpatient
      admissions.

PMID- 8284060
TI  - The area support medical battalion: a concept validated by Operation Desert
      Shield/Storm.
AB  - Operation Desert Shield/Storm provided an opportunity to evaluate current medical
      assets and doctrine in support of Army air-land battle operations. The missions
      assigned to a medical company (clearing) during Operation Desert Shield/Storm
      demonstrated the value of the area support medical battalion as authorized under
      Medical Force 2000. The battalion, with a few personnel additions and advanced
      training, could have met all the challenges faced by the medical company
      (clearing). With the military's drawdown, units must be created which can operate
      efficiently and react to anticipated demands.

PMID- 8284061
TI  - Leishmaniasis among Desert Storm veterans: a diagnostic and therapeutic dilemma.
AB  - Troops stationed in the Middle East during Operations Desert Shield/Storm were
      potentially exposed to leishmaniasis, a parasitic infection transmitted by
      sandflies. In this region, infection primarily causes cutaneous and, less often,
      visceral disease. Visceral leishmaniasis, which typically has an incubation
      period of several months, can be a difficult diagnosis as it presents with a wide
      range of symptoms and there are no non-invasive, reliable diagnostic tests.
      Cutaneous leishmaniasis is more easily diagnosed using culture and stained smears
      of biopsy and aspirate samples from skin lesions. Pentavalent antimonials are
      most often used to treat leishmaniasis; however, treatment is potentially toxic
      and not recommended except in cases of documented disease.

PMID- 8284062
TI  - The Navy Forward Laboratory during Operations Desert Shield/Desert Storm.
AB  - The Navy Forward Laboratory (NFL) was an advanced infectious disease laboratory
      which provided a theater-wide reference diagnostic capability during Operations
      Desert Shield/Storm. During Operation Desert Shield, when massive numbers of
      troops were being deployed, the NFL primarily supported medical personnel in the
      diagnosis and treatment of infectious diseases. During the war, the laboratory
      provided rapid biologic warfare diagnostic support. The NFL demonstrated the
      benefits of a comprehensive, on-site diagnostic laboratory when large numbers of
      troops are deployed to high-risk areas and demonstrated the importance of
      military medical research laboratories for training of scientists and physicians,
      threat assessment, and product development.

PMID- 8284063
TI  - Mobile surgical hospital design: lessons from 5th MASH surgical packages for
      Operations Desert Shield/Desert Storm.
AB  - Operations Desert Shield/Desert Storm defined and tested a number of assumptions
      about the abilities of the Mobile Army Surgical Hospital. These assumptions
      involved the adequacies of mobility, both strategic and tactical, the number of
      hospital beds, surgical capability, and set-up time. This article reviews the
      characteristics, staffing, and surgical abilities of the four types of surgical
      packages deployed by the 5th Mobile Army Surgical Hospital in response to the
      changing patient care and tactical situation. These packages were the Forward
      Surgical Team, Forward Surgical Element, Mobile Army Surgical Hospital(-), and
      Mobile Army Surgical Hospital. Seven variables as they relate to hospital weight
      and cubic space are introduced. Mobility and surgical ability are emphasized as
      the first and second highest priority to consider in a proposed methodology when
      developing Mobile Army Surgical Hospitals.

PMID- 8284064
TI  - Potential risk factors for overtreatment in military dentistry.
AB  - Recent studies in the National Health Service in Scotland have suggested that
      frequent changes of dentist, and frequent dental examinations, subject
      individuals to an increased risk of receiving dental treatment. The present study
      tested the influence of these two factors on dental health changes, the amount of
      dental treatment received, and restoration longevity in a population of 100 long
      term members of the Royal Australian Air Force. Despite the predictions possible
      from the Scottish research, the present study failed to find any significant
      links between frequent attendance or frequent change of dentist and dental health
      or restoration longevity. However, the type of treatment provided appeared to be
      influenced by frequency of attendance and military rank.

PMID- 8284065
TI  - Evaluation of focal carotid ischemia: will duplex scanning suffice, or is
      angiography needed?
AB  - We compared duplex scanning and cerebral angiography in patients with hemispheric
      ischemia, testing the premise that carotid endarterectomy (CEA) or medical
      management may be recommended on the basis of duplex scanning alone. Charts of
      152 patients who had both studies were reviewed. A positive study (implying an
      operable lesion) showed any ulcerated plaque or stenosis of 50% to 99% on the
      symptomatic side. A positive duplex scan correctly predicted the need for CEA
      (with no additional essential information gained from angiography) more than 98%
      of the time. Equally important, patients with a negative duplex or patients in
      whom carotid occlusion is suspected ought to have angiography.

PMID- 8284066
TI  - Alcohol: the clinician's role in evaluating legal responsibility.
AB  - Alcohol-related misconduct poses a challenge for society, the legal system, and
      the medical profession. The debate is centered on alcohol abuse and the
      determination of responsibility for misbehavior. In assessing responsibility, the
      legal system often requests the expertise of the medical professional. The
      knowledgeable clinician can contribute to the just resolution of complex medico
      legal cases. The best contribution considers medical facts in relation to the
      evolution of legal thinking. This article explores the historical, social, and
      legal approaches to alcohol-related misconduct. The article concludes with a
      discussion of a model clinical assessment.

PMID- 8284067
TI  - Venous ulceration of the hand secondary to a cimino fistula.
AB  - Cimino fistula is an anastomosis created for chronic hemodialysis, between the
      radial artery and cephalic vein near the wrist. Its complications include
      thrombosis (most frequent), infection, congestive heart failure, arterial
      insufficiency, venous hypertension, vascular access neuropathy, and aneurysms. Of
      these, venous hypertension appears to occur rarely. We report here a case where
      it resulted in pigmentation, swelling, and ulceration of the middle finger. It
      was surgically treated, without ligating the arteriovenous fistula, by selective
      ligation of tributaries from the affected fingers.

PMID- 8284068
TI  - Oral diagnostic sciences: a "keystone" of the future.

PMID- 8284069
TI  - Levamisole in erythema multiforme.

PMID- 8284070
TI  - Single dose and multidose analgesic study of ibuprofen and meclofenamate sodium
      after third molar surgery.
AB  - The purpose of this study was to compare the analgesic efficacy and safety of
      meclofenamate sodium with ibuprofen after dental impaction surgery. This study
      was double-blind and used a unique methodology. Patients (N = 254) were first
      randomized into the single dose phase of the study that included placebo,
      meclofenamate 50 mg, meclofenamate 100 mg, ibuprofen 200 mg, and ibuprofen 400
      mg, followed by a 7-day multidose phase in which patients in the placebo group
      were rerandomized into one of the active treatment cells. In the single dose
      phase, all active treatments were significantly more efficacious than placebo for
      every summary analgesic measure. A positive dose-response was seen for both
      active drugs with meclofenamate 100 mg and ibuprofen 400 mg exhibiting the
      greatest efficacy for pain relief, pain reduction, time to remedication, and
      overall evaluation. Side effects were reported by 26 patients. They were evenly
      distributed among treatment groups with headache and drowsiness being the most
      common. During the multidose phase, there were only small differences in efficacy
      measures among active treatment groups. However, meclofenamate produced a higher
      incidence of stomach cramps and diarrhea than did ibuprofen (8.8% and 7.2% versus
      0.8% and 0.8%). This study indicates that higher doses of nonsteroidal anti
      inflammatory drugs are most effective immediately after surgery and that lower
      doses of these drugs can be used after the first postoperative day. The side
      effect profile of nonsteroidal anti-inflammatory analgesics is best observed with
      the use of a multidose study design.

PMID- 8284071
TI  - Prognosis of third molar eruption.
AB  - This study was designed to find a threshold value for an increased probability of
      upper and lower third molar eruption measured on rotational tomograms compared
      with lateral cephalometric radiographs. Twenty-seven patients had been followed
      over a 7-year period. Space available in the retromolar region had been measured
      at mean ages of 13, 16, and 20 years. At early ages, patients with erupted third
      molars had significantly more space available in the retromolar region. More
      wisdom teeth had erupted with a space/width ratio > or = 1 measured on rational
      tomograms and a distance of 25 mm or more on lateral cephalometric radiographs.
      There was a strong correlation between rotational tomograms and lateral
      cephalometric radiograph measurements as well as good reliability and
      reproducibility compared with study casts.

PMID- 8284072
TI  - Comparison of the clinical status of third molars in young men in 1949 and in
      1990.
AB  - We investigated the clinical status of third molars in 876 Finnish conscripts
      aged 19.9 years (SD, 1.1 years) and compared the findings with data on male
      students of the same age from 40 years before. Significantly more partially
      erupted and fewer totally erupted lower third molars were found in the present
      study than 40 years earlier: 29% (95% confidence interval +/- 3%) versus 19% were
      partially erupted (p > 0.001), and 13% (confidence interval +/- 3%) versus 23%
      were totally erupted (p < 0.001). Fifty-eight percent of the lower third molars
      in the present study were clinically missing, whereas 13% (confidence interval +/
      2%) were totally erupted. The respective percentages in the upper jaw were 56%
      (confidence interval +/- 3%) versus 38% (confidence interval +/- 3%). Thirty
      eight percent (confidence interval +/- 3%) of our subjects had one or two
      partially erupted third molars in the mandible and 10% (confidence interval +/-
      2%) in the maxilla.

PMID- 8284073
TI  - Predictive model for impaction of lower third molars.
AB  - The study was carried out to create and test a model for predicting impaction of
      lower third molars on the basis of radiographic findings at age 20 years. Fifty
      six initially unerupted lower third molars were followed up for 6 years. Five
      radiographic findings in panoramic tomograms at age 20 were taken as variables.
      Clinical status at age 26 was taken as response. The radiographic features
      studied were angulation of tooth, development of root, state of impaction, depth
      in bone, and relation of the tooth to the ramus of the mandible and the second
      molar. With the use of logistic regression, univariate and bivariate analyses,
      and clustering techniques, a decision tree was constructed that indicated
      accuracies of prediction on the basis of single variables or pairs of variables.
      The most important predictor was the type of impaction. The model predictions and
      test teeth findings were in agreement in 94% of instances. It was concluded that
      the model is suitable for predicting lower third molar impaction at age 20.

PMID- 8284074
TI  - Fluconazole-resistant Candida in AIDS patients. Report of two cases.
AB  - Oropharyngeal candidiasis develops in up to 95% of patients with acquired
      immunodeficiency syndrome. Oral fluconazole is frequently prescribed for persons
      who are human immunodeficiency virus-seropositive as initial or suppressive
      therapy for oropharyngeal and esophageal candidiasis or as suppressive therapy
      for cryptococcal meningitis. We report two cases of oropharyngeal candidiasis,
      caused by Candida albicans, which developed in two patients with acquired
      immunodeficiency syndrome who had taken fluconazole for extended periods. In
      addition to the clinical resistance we observed, isolates of the organism
      appeared to be resistant in vitro to fluconazole and ketoconazole.

PMID- 8284075
TI  - Multiple cutaneous leiomyomas. Report of a case.
AB  - Multiple cutaneous leiomyomas usually appear as painful nodules of the skin.
      Historically these have been treated by surgical excision, however, because they
      are often numerous, surgery may be an impractical approach. This article reports
      on a patient with multiple leiomyomas of the face treated by excision as well as
      a discussion of alternative treatments such as pharmacologic agents that may be
      used when surgical excision is not feasible.

PMID- 8284076
TI  - Vitamin C enhances the development of carcinomas in the hamster buccal pouch
      experimental model.
AB  - Forty young adult male Syrian hamsters (Mesocricetus auratus) were divided into
      four groups of 10 animals. The animals in group 1 (tumor control) had the right
      buccal pouches painted three times a week with a 0.5% solution of 7,12
      dimethylbenz(a)anthracene in heavy mineral oil USP with the use of a number 4
      sable brush. The animals in group 2 (experimental group) had the right buccal
      pouches painted with the same solution as group 1. In addition, they received 1
      mg ascorbic acid in 0.5 ml mineral oil three times a week on days alternating
      with the other application. The ascorbic acid was administered by mouth with the
      use of a pipette. The animals in group 3 received 1 mg ascorbic acid in 0.5 ml
      mineral oil three times weekly, and the animals in group 4 were untreated
      controls. The animals were killed after 14 weeks. Tumors were counted and
      measured. Both right and left (control) pouches were photographed, excised, fixed
      in formalin, sectioned in paraffin, and studied histologically. The animals that
      received the ascorbic acid (vitamin C) had significantly larger tumors in the
      right buccal pouch, although actual numbers of gross tumors were only slightly
      increased. The figures for tumor burden in the animals in groups 1 and 2 were 364
      versus 648 mm3. Histologic study revealed that the animals in group 2 had more
      anaplastic tumors and a significantly greater number of areas of dysplastic
      leukoplakia than the animals in group 1.

PMID- 8284078
TI  - Effects of snuff on regional blood flow to the cheek and tongue of anesthetized
      dogs.
AB  - Regional blood flow to the cheek and tongue of anesthetized dogs was measured
      before and after application of six different doses of snuff (3.12 to 100 mg/kg
      body weight) to the right cheek. Dose-independent vasodilation was observed at
      the site of application, whereas dose-dependent vasoconstriction was observed
      contralaterally. Aortic, central venous, and ventricular pressures were
      significantly increased (p < 0.05) at the higher doses. Plasma nicotine
      concentrations increased stepwise with dose.

PMID- 8284077
TI  - Effects of sialoadenectomy and epidermal growth factor administration on 9,10
      dimethyl-1,2-benzanthracene-induced tumor formation in hamster cheek pouch.
AB  - The effects of removal of the submandibular gland (sialoadenectomy) and
      administration of human urinary epidermal growth factor on the 9,10-dimethyl-1,2
      benzanthracene-induced tumor formation were investigated with the use of a
      hamster cheek pouch model. Syrian hamsters were treated with 0.5% 9,10-dimethyl
      1,2-benzanthracene for 6 weeks. Thereafter hamsters in group 1 underwent a sham
      operation and those in groups 2 and 3 underwent a sialoadenectomy. Subsequently,
      hamsters in groups 1 and 2 were given 0.9% sodium chloride and group 3 received
      the human urinary epidermal growth factor at a dose of 0.25 mg/kg body weight
      subcutaneously three times a week for 8 weeks. Sixteen weeks after the start of
      the experiment, the mean number of tumors that were less than 3-mm in diameter in
      groups 1 and 3 was significantly greater than that in group 2 (p < 0.05). The
      overall incidence and mean number of all carcinomas irrespective of size showed
      no differences among the experimental groups. These results indicate that
      epidermal growth factor synthesized in the submandibular gland may enhance the
      induction of cheek pouch tumor.

PMID- 8284079
TI  - Oral epithelial response to experimental chronic alcohol ingestion in hamsters.
AB  - The purpose of this study was to assess the effect of alcohol on oral epithelium
      by quantifying epithelial compartment thicknesses after chronic alcohol ingestion
      with the use of a computerized planimetry system. A 10% solution of absolute
      alcohol in water was given as the sole source of drinking fluid to young adult
      Syrian hamsters over a period of 9 months. Quantitative histologic analysis
      showed significant atrophy of the posterior lateral tongue epithelium. The
      epithelium of the dorsal tongue showed an increase in the thickness percentage of
      keratin. No significant change was found in the ventral aspect of the tongue
      epithelium. It was concluded that such alcohol-related atrophy may render the
      lateral margins of the posterior tongue more susceptible to carcinogenesis.

PMID- 8284080
TI  - Langerhans cells in oral mucosa of rhesus monkeys before and after infection by
      simian retrovirus-1 and simian immunodeficiency virus.
AB  - To study the influence of experimental infection with simian retrovirus-1 and
      simian immunodeficiency virus on the number and distribution of Langerhans cells
      in oral mucosa of rhesus monkeys, 10 monkeys were intravenously inoculated with
      simian retrovirus-1, 7 with simian immunodeficiency virus, and 2 were mock
      inoculated. Biopsies were taken from gingiva and cheek pouch before infection and
      at 1 (simian immunodeficiency virus group only), 4, and 7 months after infection.
      Langerhans cells were detected in frozen sections by immunohistochemistry with
      monoclonal antibodies Leu-6 and HLA-DR. The mean number of Langerhans cells per
      surface millimeter and square millimeter of epithelium was calculated under blind
      conditions. The results showed no statistically significant differences in the
      number or distribution of Langerhans cells in the three groups at the various
      time points of examination. Similarly, no differences were detected within any
      group over the observation period. Thus systemic infection of rhesus monkeys with
      either simian retrovirus-1 or simian immunodeficiency virus does not lead to a
      significant change in the number of Langerhans cells in oral mucosal epithelium.

PMID- 8284081
TI  - Metastatic mesothelioma of the oral cavity. Report of two cases.
AB  - Malignant mesothelioma is an aggressive neoplasm originating from the serosal
      surfaces of the pleural or peritoneal cavity. The following article describes two
      cases of metastatic mesothelioma to the oral cavity; one involves the tongue, the
      other involves the mandible. The diagnostic criteria for differentiating
      metastatic mesothelioma from adenocarcinoma are also discussed.

PMID- 8284082
TI  - Metastatic breast carcinoma mandible in gynecomastia gynecomastic. Case report.
AB  - This is a rare case of breast carcinoma with metastasis to the jaw in a
      relatively young man with gynecomastia. Immunohistochemical studies suggest a
      stage differentiation arrest in ductal cells.

PMID- 8284083
TI  - Effect of post preparation on the apical seal of teeth obturated with plastic
      thermafil obturators.
AB  - The effect of post canal preparation on the apical seal of endodontically
      obturated teeth with plastic Thermafil obturators was studied in vitro. Fifty
      four extracted human maxillary anterior teeth were divided into four experimental
      and two control groups. Two groups were obturated with lateral condensation or
      plastic Thermafil obturator techniques; this was followed by post space
      preparation. Two groups were obturated as described above except that post space
      was not prepared. Apical leakage was determined with the use of 2% methylene blue
      dye solution at an absolute pressure of 75 mm Hg. There were no statistically
      significant differences between any of the groups. The clinical implication of
      these findings is discussed.

PMID- 8284084
TI  - Dimensional changes of endodontic sealers.
AB  - The purpose of this study was a long-term comparison of the dimensional changes
      of endodontic sealers of diverse properties. The sealers were injected as thin
      layers on the internal walls of glass pipettes 1 mm in diameter. The pipettes
      were filled with deionized water, and the water meniscus levels were recorded
      periodically up to 180 days. The water was removed from the pipettes, samples
      were allowed to dry, and the mass and the volume of the sealers were measured.
      AH26 and Endo-Fill had an initial expansion followed by a volumetric loss. The
      two zinc oxide eugenol-based sealers studied started to shrink within hours after
      mixing; the first volumetric loss for AH26 was recorded during the first 30 days
      and for Endo-Fill after 30 days. The least dimensional change at any time was
      observed for Endo-Fill. It was concluded that a significant dimensional change
      and continued volume loss can occur in some endodontic sealers.

PMID- 8284085
TI  - Multimodality imaging of cervicofacial actinomycosis.
AB  - Actinomycosis is an uncommon chronic disease usually caused by Actinomyces
      israelii. It affects the soft tissue mainly but sometimes spreads to involve
      salivary glands, bone, or even the skin of the face and neck. Five cases have
      been seen in our department. Several imaging modalities were used to assist in
      making the diagnosis. The cases are presented and the literature reviewed.
      Ultrasonography was found to be a useful diagnostic tool especially in developing
      the differential diagnosis.

PMID- 8284086
TI  - Magnetic resonance imaging of oral and maxillofacial angiomas.
AB  - Eleven patients with oral and maxillofacial angiomas (seven hemangiomas and four
      lymphangiomas) were evaluated with magnetic resonance imaging using a 0.2-T
      permanent system and spin-echo pulse sequences. These lesions typically had
      signal intensities that were iso T1-weighted, similar to muscle, and high T2
      weighted, greater than subcutaneous fat. Nine tumors had well- or relatively well
      defined margins, and seven cases had curvilinear structures of low signal
      intensities in the masses on T2-weighted images. It was impossible to distinguish
      hemangiomas from lymphangiomas on MR images. Our experience suggested that most
      angiomas of oral and maxillofacial regions present special characteristics on
      magnetic resonance images. It is thought that information obtained with magnetic
      resonance images can contribute significantly to the evaluation of the extent of
      these lesions.

PMID- 8284087
TI  - Aneurysmal bone cyst versus hemangioma of the mandible. Report of a long-term
      follow-up of a self-limiting case.
AB  - The aneurysmal bone cyst is an enigmatic and misnamed lesion displaying variable
      etiopathogenic and histologic characteristics. The aneurysmal bone cyst may
      appear as a primary lesion or as a secondary lesion associated with other
      pathologic entities. This article presents a probable self-limiting lesion that
      provides an opportunity to present an approach to classifying aneurysmal bone
      lesions.

PMID- 8284088
TI  - Experimental and clinical studies on dose reduction effects of spacers in
      interstitial brachytherapy for carcinoma of the mobile tongue.
AB  - The difference of radiation dose reduction effect with spacers of different
      materials, a heat-curing denture base resin and a silicon impression material,
      was examined experimentally and clinically. Radium needles and iridium hairpins
      were used as radioactive sources. In both studies, it was revealed that a dose
      reduction effect of silicon impression material was greater than that of denture
      base resin. Silicon impression material was thought to be a better material for
      spacers because of its larger radiation dose reduction effect and the time saving
      to produce the spacer.

PMID- 8284089
TI  - A comparison of self-perceived clinical competencies in primary care residency
      graduates.
AB  - One hundred seventy-eight graduates from four primary care residency training
      programs with common hospital sites (medicine/pediatrics, 72; family medicine,
      29; pediatrics, 35; and internal medicine, 42) responded to a mailed survey
      questionnaire regarding distribution of professional time and self-perceived
      clinical competencies. Most of the internists, family physicians, and
      internist/pediatricians (MED/PED) were in primary care, and 57% of the
      pediatricians were subspecialists. Respondents rated each of 24 clinical
      vignettes as to their level of comfort in managing the patient problems
      presented. MED/PED and pediatricians responded similarly to all the infant,
      child, and adolescent cases. Family physicians were less comfortable in managing
      the complicated neonatal situations but more comfortable with adolescent health
      care than the MED/PED or pediatricians. MED/PED reported greater comfort than
      family physicians in complex internal medicine issues, but less than internists
      in intensive care and geriatric consultation. Significant differences in reported
      competency existed among these primary care practitioners despite substantially
      overlapping training backgrounds.

PMID- 8284090
TI  - Immunomodulating actions of nucleotides: enhancement of immunoglobulin production
      by human cord blood lymphocytes.
AB  - We have shown previously that polynucleotides enhance in vitro antibody and Ig
      production in response to T-dependent antigens in mice and augment Ig production
      by adult human peripheral blood mononuclear cells. Herein, we report their
      effects on umbilical cord blood mononuclear cells (CBMNC) obtained from full-term
      babies. CBMNC produced much less IgM/IgG and an almost negligible amount of IgA
      in response to various stimuli compared with adult peripheral blood mononuclear
      cells. The supplementation of yeast RNA augmented spontaneous and T-dependent IgM
      (p < 0.01) but not IgG production by CBMNC. This action was largely attributable
      to polynucleotides, which appeared to exert their actions in a dose-dependent
      manner at the initial stages of culture. Their actions were dependent upon the
      presence of T cells, but they also enhanced spontaneous IgM production by CBMNC
      in the absence of T cells. Preincubation of T cells from CBMNC and peripheral
      blood mononuclear cells with RNA for 3 h before the culture resulted in enhanced
      IgM production, independent of the stimulants used. Thus, polynucleotides appear
      to exert actions on immature human T cells as well as other lineage cells in
      vitro. Their actions may be dependent on the presence or absence of antigens or
      other stimuli and the nature of the stimuli (T dependent versus T independent).
      These findings may further support the potential importance of nucleotides
      contained in human breast milk.

PMID- 8284091
TI  - Nucleotide depletion due to reactive oxygen metabolites in endothelial cells:
      effects of antioxidants and 3-aminobenzamide.
AB  - Reactive oxygen metabolites have an important role in ischemia-reperfusion
      injury. One of the sources of reactive oxygen metabolites is xanthine oxidase,
      which is present in several tissues but is also released into the circulation
      after ischemia. We studied the effect of several potentially protective compounds
      on adenine nucleotide depletion induced by extracellular xanthine oxidase and
      hypoxanthine, in concentrations relevant to human pathophysiology. In umbilical
      vein endothelial cells prelabeled with 14C-adenine, cellular adenine nucleotides
      retained 64 +/- 9% of the initial radioactivity over a 4-h incubation with
      culture medium (controls), whereas in the presence of xanthine oxidase (80 mU/mL)
      and hypoxanthine (100 microM), only 3 +/- 4% of radioactivity remained in
      cellular nucleotides, the rest appearing in catabolic products in the medium.
      Glutathione and 3-aminobenzamide, an inhibitor of poly-ADP-ribose polymerase,
      partly prevented the nucleotide depletion (adenine nucleotide radioactivity 15 +/
      6% to 33 +/- 13% of total), but scavengers of the hydroxyl radical,
      dimethylthiourea and DMSO, as well as vitamins E and C, were without effect.
      Superoxide dismutase prevented the leakage of nucleotides into the culture medium
      but not intracellular nucleotide catabolism, whereas the latter process was
      decreased by catalase, consistent with predominant effects of superoxide and
      hydrogen peroxide at the cell membrane and interior, respectively.

PMID- 8284092
TI  - Epidermal growth factor increases antioxidant enzyme and surfactant system
      development during hyperoxia and protects fetal rat lungs in vitro from hyperoxic
      toxicity.
AB  - Epidermal growth factor (EGF) has been shown to accelerate fetal lung maturation
      in rabbits, lambs, and rhesus monkeys in vivo and increase surfactant synthesis
      in vitro. Its effect on the maturation of the lung antioxidant enzyme system,
      however, is unknown. We studied the effect of EGF (10 nM) on 19-d fetal rat lung
      explant cultures in serum-free medium in air/5% CO2 or > 90% O2/5% CO2 compared
      with similarly grown control cultures in air or hyperoxia at 72 h. Fetal lung
      activities of superoxide dismutase and catalase were unchanged by EGF in air,
      whereas glutathione peroxidase activity was significantly decreased (p < 0.05
      versus air control). However, in hyperoxia, EGF-treated fetal lung cultures had
      significantly elevated superoxide dismutase and catalase activities (p < 0.01)
      versus O2-exposed controls, and glutathione peroxidase activity similar to that
      of controls. The mRNA levels for all the antioxidant enzymes showed patterns
      similar to the enzyme activities except in the case of Cu,Zn-superoxide dismutase
      mRNA, which increased in EGF-air cultures. EGF decreased the rate of 3H-choline
      incorporation into disaturated phosphatidylcholine in air (p < 0.01 versus air
      control), but increased disaturated phosphatidylcholine synthesis in response to
      hyperoxia (p < 0.01 versus O2 control). The histologic appearance of EGF-treated
      cultures in O2 was superior to that of O2-exposed controls, which showed
      thickened septal walls, decreased surfactant in the air spaces, and epithelial
      cell mitochondrial swelling. EGF therefore accelerates antioxidant enzyme and
      disaturated phosphatidylcholine maturation under hyperoxic conditions and
      protects fetal rat lung cultures from hyperoxic injury.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8284093
TI  - Levels of complement anaphylatoxin C5a in pulmonary effluent fluid of infants at
      risk for chronic lung disease and effects of dexamethasone treatment.
AB  - A number of studies have shown that increased numbers of neutrophils and
      macrophages are recruited into the airways during the development of chronic lung
      disease (CLD) in preterm infants. The objective of this study was to determine
      whether the anaphylatoxin C5a is detectable in tracheobronchial aspirate fluid of
      infants at risk for CLD and to evaluate the possible effects of dexamethasone
      (Dxm) treatment. C5a/C5a(des Arg) levels were determined by a sensitive ELISA
      based on a neoepitope-specific MAb. In a prospective study, 27 infants (birth
      weight 881 +/- 169 g, mean +/- SD) still on mechanical ventilation at d 10
      postnatal age with fraction of inspired oxygen > or = 0.3 and/or peak inspiratory
      pressure > or = 16 cm H2O were randomly assigned to Dxm treatment at d 10 (n =
      14) or d 16 (n = 13). Ten mechanically ventilated infants with no respiratory
      disease or who had recovered from respiratory distress syndrome did not meet
      these criteria on d 10 and served as a control group (birth weight 928 +/- 126
      g). For the evaluation of Dxm therapy, the late treatment group was used as a
      control group for the early regimen. Compared with controls, C5a concentrations
      were higher in infants at risk for CLD on d 10 [median (25th-75th percentile):
      2.40 (1.13-3.38) versus 0.82 (0.55-1.78) micrograms/L, p < 0.05].(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8284094
TI  - Postnatal adrenoreceptor maturation in porcine intrapulmonary arteries.
AB  - The effect of postnatal age on norepinephrine-induced alpha 2-adrenoreceptor
      mediated release of endothelium-derived relaxing factor in porcine intramuscular
      pulmonary arteries was studied. Rings of pulmonary artery from fetal, newborn, 3
      d-, 10-d-, 9-wk-, and 15-wk-old pigs with and without endothelium were suspended
      for isometric force measurement in Krebs-Ringer bicarbonate solution (37 degrees
      C, 95% O2-5% CO2). In 15- and 10-wk-old pigs, norepinephrine increased tone in
      arteries with and without endothelium but produced relaxations at high
      concentrations only in arteries with endothelium. These relaxations were not
      inhibited by the alpha 1-antagonist prazosin but were completely abolished by the
      alpha 2-antagonist yohimbine and the inhibitor of nitric oxide release N-omega
      nitro-L-arginine methyl ester. This confirms that the norepinephrine-induced
      relaxations were due to alpha 2-mediated release of endothelium-derived relaxing
      factor. Arteries from only 50% of the 10-d-old animals showed endothelium
      dependent relaxations, and at 3 d of age and younger no relaxations were seen. In
      animals less than 10 d old, only some of the vessels contracted to norepinephrine
      and the contractile response was diminished compared with 15-wk-old animals,
      whereas the response to prostaglandin F2 alpha and histamine was similar in the
      neonatal group (newborn, 3 d old, and 10 d old). This group showed a dose
      dependent relaxation to nitric oxide, with 10-d-old animals more sensitive to
      nitric oxide than newborn animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284095
TI  - Pulmonary capillary recruitment in neonatal lambs.
AB  - In species having lungs large enough to develop hydrostatic perfusion zones,
      increased pulmonary arterial pressure causes blood flow to be redistributed from
      the lower to the upper lung. The blood flow increase in the upper lung recruits
      capillaries and increases gas exchange surface area. There is disagreement,
      however, about whether such capillary recruitment occurs in young animals with
      small lungs. To investigate this issue, we used in vivo microscopy to directly
      study capillary perfusion in individual alveolar walls in the upper lungs of
      neonatal lambs and in older lambs with larger lungs. Pulmonary arterial pressure
      was elevated by airway hypoxia. In neonatal lambs (< 10 d old; n = 7), hypoxia
      increased pulmonary arterial pressure by 55% but did not cause capillary
      recruitment. In older lambs (20-61 d old; n = 6), hypoxia increased pulmonary
      arterial pressure by 40% and caused a 46% increase in recruited capillaries.
      These results support the hypothesis that capillary recruitment does not occur in
      newborn lambs when pulmonary arterial pressure increases and implies that there
      is limited gas exchange reserve. In older lambs, however, gas exchange reserve
      develops through recruitable capillaries as the lungs mature.

PMID- 8284096
TI  - Assisted mechanical ventilation using elastic unloading: a study in cats with
      normal and injured lungs.
AB  - Elastic unloading [otherwise known as negative ventilator compliance (Cv) or
      proportional assist ventilation] is a new mode of assisted mechanical
      ventilation. The ventilator continuously measures the volume of spontaneous
      breathing (V) and adjusts the pressure at the airway opening in proportion to V.
      The quotient of pressure above the baseline end-expiratory level per unit of V
      (the gain of the assist) is constant at any point in time and can be preset. The
      apparatus used for this study can also generate elastic loading (positive Cv) by
      decreasing the pressure at the airway opening in proportion to V. This might be
      useful during the weaning process. This study compares measured values of total
      compliance of the combined lung-respirator system (Ctot) with values predicted
      according to theory, where 1/Ctot = 1/Cv + 1/Cl with Cl being the lung
      compliance. Respiratory mechanical data were derived from esophageal pressure and
      airflow in eight anesthetized, intubated, spontaneously breathing cats. Different
      Cv levels were set on the ventilator both before and after lung injury with
      xanthine oxidase. The difference (mean +/- SD) between the measured and predicted
      Ctot was 1.4 +/- 21.4% (healthy lungs) and -11.6 +/- 14.1% (injured lungs) during
      unloading and 2.5 +/- 7.5% (healthy lungs) during elastic loading. An elevation
      of Ctot decreased the expiratory airflow. Tidal volume increased slightly in
      healthy lungs and arterial PCO2 decreased. We conclude that the effects of Cv on
      the total compliance of the combined lung-respirator system can accurately be
      predicted.

PMID- 8284097
TI  - How to ventilate lungs as small as 12.5% of normal: the new technique of
      intratracheal pulmonary ventilation.
AB  - We wished to determine in a laboratory animal model how much residual lung was
      needed to sustain total gas exchange. In a series of young, healthy lambs
      weighing approximately 10 kg that were sedated and paralyzed, we progressively
      excluded from gas exchange all the left lung (a total of 43%), plus the right
      lower and cardiac lobes (81%), plus the right middle lobe (87.5%). In some
      studies, the respective lobes were surgically removed; in others, the bronchi and
      the pulmonary arteries to the respective lobes were ligated. We provided
      pulmonary ventilation using the pressure control mode (Servo 900 C) at a tidal
      volume of 20 mL/kg multiplied by the fraction of the remaining lungs, a
      respiratory rate up to 120/min, a peak inspiratory pressure of 12-15 cm H2O, and
      a positive end-expiratory pressure of 3 cm H2O. Those lambs with at least both
      the right upper lobe (RUL) and right middle lobe remaining (19% of total lungs)
      were weaned to room air on mechanical ventilation within 48 h. Ventilating RUL
      (12.5% of remaining lung) with the same ventilator required a substantially
      higher tidal volume and peak inspiratory pressure to result in adequate alveolar
      ventilation but led to respiratory failure and death within 8 h. We then applied
      a newly developed system of intratracheal pulmonary ventilation to ventilate the
      RUL (12.5% of remaining lung) alone. A continuous flow of humidified mixture of
      air and oxygen was directly passed into the trachea at the level of the carina
      through a diffuser at a tidal volume of 2.5 mL/kg. A single valve controlled
      expiration and respiratory rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284098
TI  - Respiratory function in lambs after prolonged oligohydramnios during late
      gestation.
AB  - Our aim was to determine the effects of oligohydramnios during the last third of
      ovine gestation on respiratory function in lambs during their first postnatal
      month. To induce oligohydramnios, amniotic and allantoic fluids were drained from
      pregnant ewes, starting at 109.0 +/- 2.3 d of pregnancy (term approximately 148
      d). In 10 lambs born at term, respiratory function was studied four times at
      weekly intervals; a group of nine lambs from normal pregnancies served as
      controls. Over the 4-wk study period, treated lambs had significantly higher
      breathing rates and smaller tidal volumes than controls, although the differences
      diminished with age. Minute ventilation and O2 consumption were the same in each
      group, and when related to body weight, both declined with age. Treated lambs
      were normoxemic but were hypercapnic compared with controls for up to 4 wk.
      Functional residual capacity, measured by helium dilution, was the same in each
      group and increased with age. Static compliance of the respiratory system was
      lower in treated lambs up to 4 wk; lung compliances were the same in each group,
      but chest wall compliance was lower in treated lambs than in controls for 4 wk.
      Postmortem measurements, at 27-28 d, of pulmonary dry weights, DNA contents, and
      protein contents suggest that the lungs of treated lambs may have been mildly
      hypoplastic. We conclude that oligohydramnios causes a decreased chest wall
      compliance, which leads to rapid, shallow breathing and a mild hypercapnia
      lasting for at least 4 postnatal wk.

PMID- 8284099
TI  - Development of heart rate dynamics during sleep-waking states in normal infants.
AB  - Previous studies show alterations in the dynamic patterns of cardiac rate in
      several "at-risk" populations, including apparently healthy infants who
      subsequently die of the sudden infant death syndrome. In the present study, we
      examined the maturation of cardiac rate dynamics in normal infants during sleep
      waking states over the first 6 mo of life. Instantaneous changes in cardiac R-R
      intervals were examined in 12-h recordings of 24 normal full-term infants; each
      infant was recorded at 1 wk and at 1, 2, 3, 4, and 6 mo of age. Scatter plots,
      consisting of each cardiac R-R interval plotted as a function of the previous
      interval (Poincare plots), were constructed for each sleep-waking state in each
      recording. Analyses of variance were performed on the dispersion of intervals
      after long and short R-R intervals. In neonates, Poincare plots showed
      significantly more next-interval dispersion after a long R-R interval than after
      a short interval, a pattern similar to those observed in older infants and in
      healthy adults. However, between 1 wk and 1 mo of age, this pattern disappeared
      and returned gradually beginning at 2 mo of age. The scatter of points in
      Poincare plots of infants 1 mo of age approached the patterns of at-risk
      populations, including infants who subsequently died of the sudden infant death
      syndrome. These patterns at 1 mo may be indicative of increased vulnerability in
      normal infants after the neonatal period.

PMID- 8284100
TI  - Sleep state organization in premature infants of less than 35 weeks' gestational
      age.
AB  - To assess sleep organization in premature infants of < 35 wk gestational age (w
      GA), we performed polygraphic recordings in 24 neurologically normal neonates
      (eight per group): artificially ventilated 27-30 and 31-34 w GA infants and
      nonventilated 31-34 w GA infants. Sleep states were defined by concordance of EEG
      and rapid eye movement criteria. Uninterrupted active sleep periods of > 13 min
      and quiet sleep periods of > 5 min were observed in all babies, except in one 33
      w GA ventilated infant. Intervals from the beginning of recording to the 1st
      quiet sleep period varied from 0 to 63 min and intervals to the beginning of the
      longest sleep cycle varied from 5 to 84 min. Nonventilated 31-34 w GA infants had
      longer sleep cycles (p < 0.02), principally because of longer active sleep
      periods. However, percentages of different states in the cycles were similar in
      all groups. When body movements were required for state definition, amounts of
      active and quiet sleep diminished and the percentage of indeterminate sleep was
      augmented significantly. In conclusion, our study demonstrated that 1) sleep
      state differentiation is present as soon as 27 w GA; and 2) artificial
      ventilation, performed in a highly specialized neonatal intensive care unit, does
      not modify sleep organization of neurologically normal premature infants. We
      hypothesize that this "earlier" sleep state differentiation, compared with
      previous data, may be related to improvements in neonatal intensive care over
      recent years.

PMID- 8284101
TI  - Reversible brainstem auditory evoked potential abnormalities in jaundiced Gunn
      rats given sulfonamide.
AB  - Neurologic and audiologic sequelae produced by bilirubin toxicity are preventable
      by appropriately timed therapeutic intervention. To understand the timing and
      reversibility of the neural dysfunction that follows exposure to bilirubin, we
      recorded brainstem auditory evoked potentials (BAEP) in the Gunn rat model of
      bilirubin encephalopathy. Abnormal BAEP occur in jaundiced Gunn rats after
      injection of sulfadimethoxine (sulfa) 100 mg/kg intraperitoneally, which
      displaces bilirubin from blood albumin binding sites and promotes the net
      transfer of bilirubin into brain tissue. Reversal of BAEP abnormalities with
      injection of human serum albumin (HSA) 2 g/kg intraperitoneally was studied in 17
      to 20-d-old jaundiced Gunn rats. One animal from each of 14 litters was randomly
      assigned to one of the following treatment groups: 1) sulfa alone, 2) sulfa + HSA
      at 2 h, 3) sulfa + HSA at 8 h, or 4) saline alone. BAEP were recorded in each rat
      before and 0.1, 4, 8, 24, and 48 h after injection of sulfa or saline. BAEP I-II
      interwave intervals increased in all sulfa groups (p < 10(-9) to 0.27 ms (21%)
      above baseline at 8 h for the two sulfa groups not receiving treatment before
      that time (p = 0.0002), but increased less for the sulfa group given HSA at 2 h
      compared with untreated animals (p = 0.02). Partial recovery of function occurred
      at 24 and 48 h for both HSA-treated groups compared with their 8-h values (p =
      0.001), and there was increased mortality at 24 h for the sulfa group not treated
      with HSA (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284102
TI  - Sulfonylurea receptor expression in rat brain: effect of chronic hypoxia during
      development.
AB  - Sulfonylurea receptors are believed to be related to ATP-sensitive potassium
      channels and play a key role during hypoxia/ischemia in the CNS. Our previous
      work has shown that these receptors in rat brainstem neurons are more important
      in the adult rat than in the newborn during hypoxia. In the present study, we
      studied the time course of postnatal development of sulfonylurea receptors in
      detail and the effect of chronic hypoxia on receptor density in newborn pups and
      adult rats exposed to hypoxia either as fetuses or as 90-d-old rats using
      receptor binding and autoradiography. Our current results show that sulfonylurea
      receptor density 1) was very low at birth and developed fast within the first 2
      postnatal wk and then gradually reached adult levels and 2) continued to increase
      in the cortex and cerebellum but decreased in the brainstem with little or no
      change in other areas after postnatal wk 5. Chronic hypoxia 1) decreased body
      weight, brain size, and brain protein concentration and 2) increased sulfonylurea
      receptor density in utero but had much less of an effect in the adult. From these
      data, we conclude that sulfonylurea receptors develop mostly in the first 2 wk
      postnatally and chronic hypoxia increases sulfonylurea receptor expression in
      utero in spite of the fact that overall protein decreases.

PMID- 8284103
TI  - Dopamine inhibits growth hormone and prolactin secretion in the human newborn.
AB  - Dopamine is frequently used in neonatal intensive care for its vasopressor, renal
      vasodilating, and cardiac inotropic properties. The effect of i.v. dopamine
      infusion on neonatal pituitary hormone secretion is currently unknown. We
      observed strikingly low serum concentrations of growth hormone (GH) and prolactin
      (PRL) during a therapeutic, standardized, isovolumetric, partial exchange
      transfusion (blood sampling every 20 min for 6 h) in two polycythemic neonates
      requiring intensive therapy, including continuous dopamine infusion. In addition,
      the secretion of GH and PRL was studied in three neonates with symptomatic
      polycythemia (gestational age 34-38 wk; birth weight 2110-2530 g; postnatal age
      10-30 h) during a partial exchange transfusion, including an intervening dopamine
      infusion (8 micrograms/kg/min i.v. for 2 h). The GH and PRL profiles were
      evaluated by deconvolution analysis. Initially, the three newborns exhibited high
      amplitude, pulsatile GH secretion and continuously elevated PRL release. During
      the dopamine infusion, GH secretion was virtually abolished and PRL release was
      reduced by at least 50%. Dopamine withdrawal was associated with a rebound
      release of GH and PRL. Finally, serum GH and PRL concentrations were studied in
      nine nonpolycythemic newborns (gestational age 31-40 wk; birth weight 1680-4000
      g; postnatal age 2-28 d) at the end of a prolonged dopamine infusion (3-5
      micrograms/kg/min i.v. for 2-27 d). Within 2 h after dopamine withdrawal, GH and
      PRL levels increased a median 3-fold and 10-fold respectively. These data concord
      to indicate that dopamine is a potent inhibitor of GH and PRL secretion in the
      human newborn.

PMID- 8284104
TI  - Pituitary-adrenal response to ether vapor in the weanling animal:
      characterization of the inhibitory effect of glucocorticoids on
      adrenocorticotropin secretion.
AB  - The hypothalamic-pituitary-adrenal axis is hyporesponsive to stimuli during early
      life in the rat. Once the adrenocortical response is established, failure to
      terminate the corticosterone (B) rise is evident after certain stressors, such as
      ether. The purpose of this study was 2-fold: 1) to investigate the B and ACTH
      response to ether vapor in young animals and 2) to test the ability of
      glucocorticoids to inhibit the ether ACTH-stimulated secretion in weanling
      animals. Rats aged 14, 18, and 25 d and adult rats were subjected to ether vapor
      for 3 min. Plasma was collected for B and ACTH determination by RIA at 0, 5, 15,
      30, 60, and 120; min after ether exposure. Maximum B levels were observed at
      different times after exposure: 15 min in the adult and 30 min in the younger
      animals. In addition, B levels were significantly elevated at 60 min in the d 25
      and d 18 rats compared with the adult (d 25 = 672.4 +/- 28.9, d 18 = 744.6 +/-
      31.7, adult = 323.2 +/- 8.7 mol/L +/- SEM; d 25 = 23.3 +/- 1.0, d 18 = 25.8 +/-
      1.1, adult = 11.2 +/- 0.3 micrograms/dL +/- SEM). The B delay observed in the
      younger animals was not due to a delayed ACTH response because maximal ACTH
      values were observed 5 min after ether exposure in all ages (d 14 = 21.9 +/- 4.8,
      d 18 = 35.8 +/- 21.3, d 25 = 82.01 +/- 16.5, adult = 98.9 +/- 25.2 x 10(-12)
      mol/L +/- SEM). However, in the d 25 rats the ACTH level remained significantly
      elevated 30 min after the ether vapor challenge (5 min = 86.9 +/- 25.2, 30 min =
      61.8 +/- 4.8, 60 min = 15.3 +/- 4.1 x 10(-12) mol/L +/- SEM). The delay to return
      to resting ACTH levels was consistent with the time delay observed for the B
      release from the adrenal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284105
TI  - Ontogeny of insulin effect in fetal sheep.
AB  - Compared with fetuses near term, midgestation fetal sheep at about 75 d of
      gestation have higher weight-specific glucose uptake rates, higher plasma glucose
      concentrations, lower plasma insulin concentrations, higher red blood cell
      insulin receptor concentrations and affinity, and a lower proportion of body
      weight accounted for by potentially insulin-sensitive skeletal muscle. Based on
      these observations, we measured the net rate of glucose uptake by the fetus from
      the uteroplacenta under basal and hyperinsulinemic conditions in eight fetal
      sheep at 76 d of gestation and eight fetal sheep at 132 d of gestation (term
      approximately 150 d). Hyperinsulinemia (414 +/- 90 pM) in the 76-d fetal sheep
      decreased plasma glucose concentration by 0.20 +/- 0.03 mM (-13%, p < 0.01) and
      increased the net rate of glucose uptake (8.4 +/- 2.2 mumol/min/kg, +21.3%, p <
      0.05) and glucose clearance (11.4 +/- 2.6 mL/min/kg, +39%, p < 0.01). In the 132
      d fetuses, a comparable hyperinsulinemia (306 +/- 36 pM) decreased plasma glucose
      concentration (-0.31 +/- 0.02 mM, -26%, p < 0.05) and increased glucose clearance
      (16.7 +/- 1.8 mL/min/kg, +73.6%, p < 0.05) to a greater extent than in the 76-d
      fetuses (p < 0.05 and p < 0.01, respectively). Net glucose uptake rate increased
      significantly in the 132-d fetuses (6.7 +/- 1.1 mumol/min/kg, +27.5%, p < 0.05),
      but not differently from the 76-d fetuses (p = 0.21). These data define brisk and
      significant effects of insulin on glucose metabolism in fetal sheep, even as
      early as approximately 50% of gestation. The midgestation fetal sheep,
      particularly in relation to its larger fractional content of body water and
      smaller fractional content of insulin-sensitive tissues, demonstrates glucose
      metabolic responses to insulin at least as great as those that occur near term.

PMID- 8284106
TI  - Amino acid (system A) transporter activity in microvillous membrane vesicles from
      the placentas of appropriate and small for gestational age babies.
AB  - Although a number of causes of poor fetal growth are known, the involvement of
      placental transport proteins in the etiology of growth retardation is not
      understood. The aim of this study was to investigate the activity of the system A
      amino acid transporter and the Na+/H+ exchanger in vesicles isolated from the
      microvillous membrane of the syncytiotrophoblast of placentas of appropriate and
      small for gestational age babies. There were no biochemical differences between
      the membranes from the two groups of placentas, and there was no difference in
      the activity of the Na+/H+ exchanger. The initial rate of uptake of
      methylaminoisobutyric acid (a nonmetabolizable amino acid analogue) was 63% lower
      in vesicles from placentas of small for gestational age babies. Kinetic analysis
      of the system A transporter (utilized by methylaminoisobutyric acid) showed that
      the Vmax in the vesicles from placentas of small for gestational age babies (0.24
      +/- 0.03 nmol/mg protein/30 s, n = 5) was significantly lower than that in
      vesicles from placentas of appropriate for gestational age babies (0.64 +/- 0.09
      nmol/mg protein/30 s, n = 4, p < 0.001), whereas the Km was not different between
      the two groups. It is concluded that there is an abnormality of system A amino
      acid transporter function in placentas of small for gestational age babies.

PMID- 8284107
TI  - In vitro studies of sodium transport in human infant colon: the influence of
      acetate.
AB  - In infants, adequate colonic function is vital in preventing electrolyte and
      water depletion. In certain species, short-chain fatty acids have been shown to
      increase colonic Na absorption. Using an in vitro voltage-clamp technique, we
      have studied the characteristics of electrolyte transport in isolated
      preparations of human left-sided colonic mucosa and investigated the effect of
      acetate on epithelial Na movement. In the basal state, there was net Na
      absorption that was entirely electrogenic. The addition of mucosal acetate
      resulted in a significant increase in net Na absorption that was markedly
      inhibited by amiloride, suggesting that, in the young child, the presence of
      short-chain fatty acids promotes colonic salvage of Na and that such salvage of
      Na may be via an amiloride-sensitive Na channel and involve stimulation of sodium
      hydrogen exchange.

PMID- 8284108
TI  - High lipoprotein(a) in children from kindreds with parental premature myocardial
      infarction.
AB  - In 98 children from 98 kindreds, 49 with and 49 without parental premature
      myocardial infarction (age < or = 45 y), our specific aim was to determine
      whether, and to what degree, lipoprotein(a) [Lp(a)] and other atherogenic lipids
      and lipoproteins might be overexpressed in children from premature infarction
      kindreds. Median Lp(a) (270 mg/L) in case boys was nearly twice that in control
      boys (140 mg/L) (p < or = 0.001). In a logistic regression model including age,
      Quetelet index (relative ponderosity), Lp(a), apo A1, apo B, triglyceride, and
      pubertal status, the 24 case boys had higher Lp(a) (p = 0.03), higher
      triglyceride (p = 0.036), and marginally lower apo A1 (p = 0.06) than the 26
      control boys. Median Lp(a) in case girls (200 mg/L) was much higher than in
      control girls (150 mg/L) (p < or = 0.01). In a logistic regression model
      including age, Quetelet index, Lp(a), apo A1, apo B, triglyceride, and menarchal
      status, Lp(a) was higher (p = 0.02), apo B was marginally higher (p = 0.07), and
      apo A1 was lower (p = 0.008) in 25 case girls than in 23 control girls.
      Reflecting familial clustering of major lipid-lipoprotein risk factors for
      coronary heart disease, children from kindreds with premature parental myocardial
      infarction were distinguished from children from control kindreds by high Lp(a)
      and also had higher apo B and triglyceride and lower apo A1 levels.

PMID- 8284109
TI  - In which neonates does early recombinant human erythropoietin treatment prevent
      anemia of prematurity? Results of a randomized, controlled study.
AB  - To assess whether erythropoietin (EPO) treatment is safe and reduces the need for
      transfusion, we randomized 44 preterm infants to an EPO group and a comparable
      control (CON) group. EPO 150 U/kg was given s.c. twice weekly for 6 wk from the
      1st wk of life. Hematologic parameters, transfusion requirements, and growth were
      followed during therapy and for 6 mo thereafter. To better assess in which
      neonates EPO treatment was effective, we classified retrospectively the EPO and
      CON groups into uncomplicated neonates (EPO A: n = 9, birth weight = 1247 +/- 126
      g, gestational age = 29.8 +/- 1.5 wk; CON A: n = 7, birth weight = 1217 +/- 145
      g, gestational age = 29.9 +/- 1.5 wk) and neonates requiring artificial
      ventilation (EPO B: n = 16, birth weight = 1169 +/- 249 g, gestational age = 28.1
      +/- 2 wk; CON B: n = 12, birth weight = 1173 +/- 215 g, gestational age = 28.3 +/
      2 wk). There were significant differences in reticulocytes between both
      uncomplicated and ventilated neonates in the EPO group compared with respective
      control groups. However, the need for transfusion was significantly less in the
      uncomplicated EPO group (EPO A: 0.44 +/- 0.73 versus CON A: 1.28 +/- 0.75, p <
      0.05) but not in the neonates on ventilation (EPO B: 8.25 +/- 5 versus CON B:
      7.75 +/- 3.7). In conclusion, early EPO administration reduces the need for
      transfusion in uncomplicated premature neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284110
TI  - Prevalence of iron deficiency in Swedish adolescents.
AB  - The prevalence of iron deficiency was determined in Goteborg, Sweden, in a sample
      of 15- to 16-y-old girls (n = 220) and boys (n = 207) using serum ferritin (SF).
      In a recent study in women on the relationship between SF and stainable bone
      marrow iron, it was established that at a cutoff value for SF of < 16
      micrograms/L in 75% of women with no iron stores SF concentration was below this
      value (sensitivity 75%), whereas in 98% of iron-replete women it was above this
      cutoff value (specificity 98%). The present study showed that in 40% of the girls
      and 15% of the boys SF was below this cutoff value, indicating iron deficiency.
      Low SF concentration was associated with significant decreases in transferrin
      saturation, Hb concentration, mean corpuscular Hb, and mean corpuscular volume.
      The results from this cross-sectional study showed that, with decreasing SF, the
      decrease of values for these parameters occurred already before SF had reached
      the level 16 micrograms/L, suggesting that SF can be validly used as a single
      criterion of iron deficiency. Using the cutoff value SF < 16 micrograms/L, the
      figures for the prevalence of iron deficiency in adolescents in different
      countries were compared and found to be rather similar in Australia, Canada, the
      United States, and Sweden. High iron requirements combined with the present low
      energy life-style leading to an insufficient supply of dietary iron may be a
      reasonable main explanation for the paradoxical, high prevalence of iron
      deficiency in adolescents in affluent societies.

PMID- 8284111
TI  - Mechanical and geometrical properties of density-separated neonatal and adult
      erythrocytes.
AB  - Neonatal red blood cells (RBC) show large variations in size, density, and
      deformability, with a relatively high percentage of neonatal RBC being extremely
      dense, almost spherical, and poorly deformable. Previous reports suggest that
      loss of membrane and oxidation of fetal Hb might account for the generation of
      the dense, rigid RBC in neonates and the shortened life-span of neonatal RBC. To
      test whether the dense RBC population is particularly fragile and which
      mechanical properties are responsible for the rigidity of these cells, the
      following measurements were made for the top (least dense) and bottom (most
      dense) 3% fractions of density-separated neonatal and adult RBC: cellular
      deformability (rheoscope); RBC geometry (micropipette system); elasticity,
      fragility, and viscosity of RBC membrane (micropipette system); Hb solution
      viscosity (cone-plate viscometer); and selected biochemical parameters. Fetal Hb
      of neonatal RBC decreased with increasing cell density. When the bottom fractions
      were compared with the top fractions, neonatal RBC showed a greater reduction in
      glutamic oxalacetic transaminase activity (72% versus 53%), potassium (39% versus
      19%), volume (32% versus 19%), and surface area (42% versus 21%), and a greater
      rise in density (3.5% versus 1.9%) and mean corpuscular Hb concentration (42%
      versus 23%) than adult RBC. Cellular deformability in the rheoscope (shear stress
      5 Pa) decreased by 24% in adults and by 41% in neonates. Membrane extensional and
      bending elastic moduli (i.e. membrane deformability) and membrane fragility of
      neonatal and adult RBC did not significantly change with increasing cell
      density.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284112
TI  - Expression and characterization of human mutant (glutamic acid304) medium-chain
      acyl-coenzyme A dehydrogenase in mammalian cells.
AB  - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a frequent and sometimes
      fatal inherited metabolic disorder of fatty acid beta-oxidation. A eukaryotic
      expression system was used to study naturally occurring mutations in MCAD. The
      1263 nucleotide coding region of human MCAD cDNA was inserted downstream of the
      SV40 early promoter for high-level expression in Chinese hamster ovary cells.
      Both normal MCAD cDNA and a mutant MCAD cDNA containing the common, disease
      causing A to G transition at position 985 (A985G), which alters a lysine to a
      glutamic acid (K304E), were inserted into expression vectors. Transient
      transfection of Chinese hamster ovary cells was performed with the expression
      constructs. The steady state level of expressed normal MCAD protein antigen was
      substantially higher (5-fold) than the expressed mutant protein. The MCAD
      enzymatic activity in protein extracts from cells containing the expressed normal
      MCAD cDNA was also much higher (6-fold) than the activity in cells expressing the
      mutant MCAD. Therefore, these data confirm that the common K304E mutation causes
      MCAD deficiency primarily by decreased protein stability rather than reduction of
      catalytic activity and, in fact, demonstrate that the K304E mutant protein has a
      similar sp act against octanoyl CoA substrate as the normal protein.

PMID- 8284113
TI  - Mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene in a patient
      with classic salt-wasting 3 beta-hydroxysteroid dehydrogenase deficiency
      congenital adrenal hyperplasia.
AB  - Inherited adrenal and gonadal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD)
      deficiency is most likely caused by a mutation of the type II 3 beta-HSD gene.
      Cloning and sequencing of exons I-II, III, and IV and portions of the adjacent
      introns, amplified by polymerase chain reaction using primers specific for the
      type II gene, in one male pseudohermaphrodite with salt-wasting classic 3 beta
      HSD deficiency congenital adrenal hyperplasia revealed the same mutation in all
      nine clones of exon IV consisting of a missense mutation at codon 248 [GTC(Val)-
      >AAC(Asn)] followed by a frameshift mutation at codon 249 [CGA (Arg)-->TA],
      resulting in a stop codon TAG, and normal sequences of exon I-II and III and the
      adjacent portions of introns. The same codon 248 and 249 mutations were found on
      one clone of his mother's DNA, but two other clones revealed normal sequences.
      These data indicate a homozygous combined missense/frameshift mutation in exon IV
      of the type II 3 beta-HSD gene resulting in severe salt-wasting adrenal and
      gonadal 3 beta-HSD deficiency in the patient.

PMID- 8284114
TI  - Primum non nocere: a pharmacologically inert pertussis toxoid alone should be the
      next pertussis vaccine.
AB  - The objective of a vaccine for pertussis is to prevent the paroxysmal cough with
      its complications. Prevention of the paroxysmal cough should prevent transmission
      of B. pertussis. Clinical studies indicate that a critical level of antitoxin
      confers protection against pertussis and that the long-lived protective immunity
      that follows pertussis is best explained by the presence of antitoxin. Vaccine
      induced protective immunity can be mediated by a critical level of antitoxin
      alone. In addition to preventing pertussis with vaccines, we predict this level
      of antitoxin will also exert epidemiologic control (herd immunity) by inhibition
      of colonization with B. pertussis and by prevention of the paroxysmal cough which
      will reduce transmission of this pathogen. Lastly, a pertussis toxoid need not
      have detectable pharmacologic activity to exert its protective actions: residual
      activity could exert a deleterious effect on glucose metabolism and exert
      immunomodulating effects. Accordingly the new pertussis vaccine should contain
      inactivated pertussis toxoid alone and there is no need to include other
      components. Several candidates could serve as a satisfactory pertussis toxoid.
      The admonition to physicians given by Hippocrates, Primum non nocere (first of
      all do no harm), should be heeded by those responsible for the development and
      use of the new pertussis vaccine.

PMID- 8284115
TI  - Deafness, complement deficiencies and immunoglobulin status in patients with
      meningococcal diseases due to uncommon serogroups.
AB  - The prevalence of deafness and complement deficiencies in association with
      meningococcal disease caused by uncommon serogroups of meningococci was studied
      in 30 patients (Group A) and 30 controls with Serogroup B disease (Group B). In
      Group A 8 patients (26.6%) had hearing impairment in contrast to only 1 patient
      (3.3%) in Group B (P < 0.01). Complement deficiency was detected in 8 patients
      (26.6%) of Group A whereas none of the Group B patients showed a defect in the
      complement system (P < 0.01). Association between complement deficiencies and
      meningococcal disease was detected for Serogroups Y (n = 5; 16.6%) and W135 (n =
      3; 10.0%). Localization of the defects revealed only complement deficiencies of
      the classical pathway (C8-beta or C7 defects). The levels of Ig and IgG
      subclasses were found to be within the normal range for all patients. Our results
      suggest that meningococcal diseases caused by uncommon serogroups are more often
      associated with deafness and late complement component defects.

PMID- 8284116
TI  - Antibody response of Navajo children primed with PRP-OMP vaccine to booster doses
      of PRP-OMP vs. HbOC vaccine.
AB  - We compared in 12- to 15-month-old American Indian infants the safety and
      immunogenicity of two licensed Haemophilus influenzae type b (Hib) conjugate
      vaccines, PRP-OMP (PedvaxHib) and HbOC (HibTITER), administered as booster
      vaccinations. All infants previously received PRP-OMP for their primary Hib
      vaccinations at 2 and 4 months of age. The geometric mean Hib antibody
      concentrations (microgram/ml) measured by radioactive antigen-binding assay for
      those receiving PRP-OMP (n = 17) or HbOC (n = 18) were 0.593 and 0.449,
      respectively, before boosting (P not significant) and 7.46 and 29.5
      micrograms/ml, respectively, after boosting (P < 0.05). PRP-OMP recipients also
      had lower geometric mean IgG anti-Hib antibody concentrations than HbOC
      recipients (7.21 vs 28 micrograms/ml, P = 0.003) and lower bactericidal titers
      (3.18 vs. 15.4, not significant). We conclude that HbOC vaccine produced a
      significantly greater booster response than PRP-OMP vaccine when given at 12 to
      15 months of age to children primed with two doses of PRP-OMP vaccine at 2 and 4
      months of age.

PMID- 8284117
TI  - Clinical severity of respiratory syncytial virus group A and B infection in
      Sydney, Australia.
AB  - Respiratory syncytial virus (RSV) has two major antigenic groups, A and B. There
      is disagreement as to whether or not there is a difference in the clinical
      severity of disease caused by the two RSV groups. This 3-year prospective study
      of infants and children with RSV-positive bronchiolitis examines the relative
      virulence of RSV Groups A and B and assesses the role that breast-feeding may
      have in modifying the clinical severity of infection. Clinical severity was
      graded I (ventilated, severe), II (oxygen therapy, moderate), III (no ventilation
      or oxygen, mild). RSV serogrouping was performed. After exclusion of 60 subjects
      with known predisposing factors for severity, 444 infants and children were
      studied (Group A, 337; Group B, 107). The difference in proportion of subjects
      with severity grade I and II with Group A compared with Group B infection was 6%
      (95% confidence interval, 4.7 to 16.7). For infants 0 to 6 months of age this
      difference was 5.6% (95% CI, 7.3 to 18.4). Nineteen cases were nosocomially
      transmitted. There was a predominance of Group A RSV infection but no difference
      in severity between Group A and Group B infection.

PMID- 8284118
TI  - Profile of enterovirus disease in the first two weeks of life.
AB  - We studied 57 infants < or = 14 days of age referred for possible enterovirus
      (EV) infection to assess the accuracy of that clinical diagnosis and describe the
      natural history of neonatal EV infection. Twenty-nine neonates proved to have EV
      infection, 23 had illnesses compatible with (but not proven to be) EV infection,
      and 5 had alternative diagnoses: bacterial infections (2); herpes simplex virus
      infection (1); and metabolic disorders (2). Neonates with proved EV infection
      were generally full term and had uncomplicated immediate postnatal periods but
      high percentages of ill contacts. Neonatal symptoms and signs included fever,
      irritability, anorexia, lethargy, hypoperfusion, rash, jaundice and respiratory
      findings. Laboratory abnormalities included cerebrospinal fluid (CSF)
      pleocytosis, chest radiograph infiltrates, abnormal urinalyses and elevated
      transaminases. EVs were most commonly isolated from CSF and rectum/stool but also
      frequently from serum and urine. Five EV-infected patients had severe multisystem
      disease (pneumonitis, hepatitis, thrombocytopenia, bleeding and meningitis),
      requiring supportive care and lengthy hospitalizations. All survived, 2 with
      residual hepatic dysfunction. Markers of severe disease included: early age of
      illness onset (especially Day 1 of life); maternal viral symptoms at delivery;
      absence of fever and irritability; tachypnea; lethargy; abdominal distension;
      hepatomegaly; and positive serum viral culture. These data support conservative
      management of ill infants < or = 2 weeks of age and suggest that antiviral
      therapy for neonatal EV infection would be optimally targeted at infants with
      early onset illness, multisystem disease and/or viremia.

PMID- 8284119
TI  - Use of nasopharyngeal isolates of Streptococcus pneumoniae and Haemophilus
      influenzae from children in Pakistan for surveillance for antimicrobial
      resistance.
AB  - Antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae
      presents a challenge to clinical case management, particularly in programs for
      acute respiratory tract infection (ARI), including pneumonia, in developing
      countries. To determine whether nasopharyngeal isolates of S. pneumoniae and H.
      influenzae from a clinically defined group of children could be used to predict
      the prevalence of antimicrobial resistance of strains that cause disease, 601
      urban children with ARI, 133 healthy urban children and 285 rural children were
      evaluated in Pakistan. Of the urban children with ARI, 216 (35.9%) were
      bacteremic, predominantly with S. pneumoniae (108 children) and H. influenzae
      (100 children). Overall 631 (61.9%) children carried S. pneumoniae and 381
      (37.4%) carried H. influenzae. The proportions of nasopharyngeal isolates of both
      organisms from urban children with ARI resistant to penicillin or ampicillin,
      trimethoprim/sulfamethoxazole, chloramphenicol and erythromycin were similar to
      the proportions of resistant blood isolates. Nasopharyngeal isolates from rural
      children had lower rates of resistance to some antimicrobial agents. These
      findings suggest that nasopharyngeal isolates of S. pneumoniae and H. influenzae
      from children with ARI can be used to conduct surveillance for antimicrobial
      resistance in a defined geographic area. Such surveillance would aid programs in
      developing countries in making a rational choice of antimicrobial agents for use
      in clinical management of bacterial diseases, including pneumonia.

PMID- 8284120
TI  - Clinical presentations and complications of suspected measles in hospitalized
      children.
AB  - We evaluated clinical presentations and complications retrospectively in 48
      pediatric patients hospitalized for suspected measles during a measles epidemic
      in Chicago. Fifty-one percent were < 15 months of age and 75% were < 4 years of
      age. Measles, diagnosed in 44 patients, was culture-proved in 18. Presentations
      were not always classic. Respiratory complications, otitis media, hepatitis,
      preterm labor, keratitis and central nervous system involvement were reported.
      The presence of stomatitis and hypotension in some patients raised the
      differential diagnoses of Kawasaki disease and toxic shock syndrome. Six patients
      with stomatitis, admitted with a measles-like illness, fulfilled the Centers for
      Disease Control and Prevention criteria for Kawasaki disease. Three were
      diagnosed with Kawasaki disease and 3 with measles. In addition to serology and
      echocardiographic changes, the platelet count and the erythrocyte sedimentation
      rate may be useful in distinguishing between measles and Kawasaki disease. Two of
      10 patients with hypotension met the Centers for Disease Control and Prevention
      criteria for toxic shock syndrome. The diagnosis of measles, solely on clinical
      grounds, may therefore not be as straightforward as is generally accepted.

PMID- 8284121
TI  - Severe Klebsiella infection as a cause of mortality in neonates in Harare,
      Zimbabwe: evidence from postmortem blood cultures.
AB  - Postmortem blood cultures were taken from 105 neonates dying at Harare Hospital
      during a 1-year period. The infants were characterized by prematurity (63% < 37
      weeks gestation), low birth weight (60% < 2500 g) and low Apgar score at 1 min
      (43% < 3). More than one-half of the infants died within 48 hours of admission.
      Positive blood cultures within 10 minutes of death occurred in 44% of infants,
      and Klebsiella sp. were by far the most common isolates. Positive blood cultures
      were associated with very low birth weight (< 1500 g), and with babies who
      survived for > 48 hours. Antibodies to human immunodeficiency virus type 1 were
      found in 40% of the infants, and a high proportion of these had Klebsiella
      bacteremia. Nearly all the infants had received antibiotic therapy, usually
      penicillin and gentamicin. Very few babies who had received a cephalosporin had a
      positive blood culture, and in vitro tests showed that although many organisms
      were resistant to penicillin and the aminoglycosides, very few showed resistance
      to the cephalosporins. Our findings suggest that cephalosporins may be useful in
      treating severe neonatal sepsis, particularly when there is no response to more
      standard therapy.

PMID- 8284122
TI  - Medical issues related to caring for human immunodeficiency virus-infected
      children in and out of the home.

PMID- 8284123
TI  - Hepatitis C virus: implications to pediatric practice.

PMID- 8284124
TI  - Hepatosplenic cat-scratch disease associated with elevated anti-Rochalimaea
      antibody titers.

PMID- 8284125
TI  - Mucormycosis of the gastrointestinal tract in children: report of a case and
      review of the literature.

PMID- 8284126
TI  - Brief surface antigenemia in newborn infants vaccinated with hepatitis B vaccine.

PMID- 8284128
TI  - Bacterial arthritis caused by Corynebacterium diphtheriae.

PMID- 8284127
TI  - Vibrio cholerae non-0:1 meningitis in an infant.

PMID- 8284129
TI  - Disseminated Scedosporium prolificans infection in an immunocompromised
      adolescent.

PMID- 8284130
TI  - Ocular lesions of tuberculosis.

PMID- 8284131
TI  - Profuse neurocysticercosis with minimal signs and a favorable outcome.

PMID- 8284132
TI  - Invasive Haemophilus influenzae disease of Melanesian and Caucasian children in
      New Caledonia.

PMID- 8284133
TI  - Overtreatment of otitis media.

PMID- 8284134
TI  - JAMA and the "Cantekin Affair".

PMID- 8284135
TI  - Chemoprophylaxis in asplenic adolescents and young adults.

PMID- 8284136
TI  - Deaf students' self-appraisals, achievement outcomes, and teachers' inferences
      about social-emotional adjustment in academic settings.
AB  - 35 deaf students completed the Self-description Questionnaire I and their
      teachers completed the Meadow/Kendall social-emotional inventory for deaf
      students. Significant positive but small correlations were found among reading
      scores, reading appraisals, and social-emotional adjustment inferences.
      Achievement, particularly reading, appears associated with concepts of self.

PMID- 8284137
TI  - Cognitive and neuropsychological characteristics of attention deficit
      hyperactivity disorder children receiving stimulant medications.
AB  - 10 children receiving stimulant medication for Attention Deficit Hyperactivity
      Disorder were compared to normal children on cognitive and neuropsychological
      dimensions in a pilot study. When compared with 10 normal children the ADHD
      children showed significant differences on cognitive measures, including the
      Wechsler Developmental Index, the Bender Visual-motor Gestalt Test, and the
      Benton Revised Visual Retention Test. Elevated levels of polyspike EEG activity
      were also noted for these children. Analysis suggested that ADHD children
      receiving stimulant medications may have persisting neuropsychological
      difficulty. Further research on the neuropsychological correlates of ADHD seems
      warranted.

PMID- 8284138
TI  - Frontal hemisphere lateralization and depressive personality traits.
AB  - To assess the relationship between hemispheric differences in information
      processing and interhemispheric asymmetries in terms of brain bioelectrical
      activity, we correlated scores on the MMPI Depression scale with interhemispheric
      asymmetry, measured as peak amplitude and latency of the P3 component of
      somatosensory evoked potentials (SEPs) at the frontocortical region of 14 healthy
      unselected volunteers (8 men and 6 women) who were about to start a course in
      autogenic training. The sample was subdivided into two groups on the basis of the
      median score on the MMPI Depression scale. Subjects scoring above the median
      showed a right lateralization at the frontocentral region and a significantly
      shorter P3 latency at the right hemisphere compared to the left.

PMID- 8284139
TI  - Cervical spine surgery and handwriting: a case report.
AB  - The 53-year-old right-handed woman underwent decompressive laminectomies and
      foraminotomies at the C3-C7 levels. The course of illness and postoperative
      recovery were documented by handwriting and MRI views, but not statistical
      analysis.

PMID- 8284140
TI  - Academic confessions of high school students: an analysis of adolescents'
      developmental concerns.
AB  - 30 normally achieving and 24 high school students with learning disabilities from
      one public high school were enrolled in an exploratory study of adolescents'
      perceptions of their learning difficulties. Adolescents completed a structured
      interview based on metacognitive and information-processing theories. Items on
      which subjects reported the most substantial problems related mainly to attention
      and organization. Comparison of the frequencies of endorsement of items for each
      group showed adolescents with learning disabilities most commonly reported
      problems with use of strategies, retrieval memory, and rapid processing. Current
      assessment methods and instructional approaches often ignore these crucial
      aspects of learning and productivity by high school students.

PMID- 8284141
TI  - Correlations of scores on the Kaufman short neuropsychological assessment
      procedure and the Kaufman Adolescent and Adult Intelligence Test for a
      hospitalized depressed sample.
AB  - Scores on the K-SNAP, a new brief cognitive measure designed to assess
      neuropsychological functioning in adolescents and adults, were correlated with
      KAIT IQs, a comprehensive test that measures fluid and crystallized intelligence.
      The sample included 33 adolescent and adult patients hospitalized for depression.
      The K-SNAP correlated significantly higher with fluid than crystallized
      intelligence.

PMID- 8284142
TI  - The anatomy of Nikyo (Aikido's second teaching).
AB  - Nikyo is the second teaching of Aikido (ni-two, kyo-teaching, in Japanese). It is
      a joint-lock technique that results in extreme pain. It allows one to control an
      opponent by destroying his will to continue fighting. Nikyo is accomplished by
      flexing and adducting an opponent's wrist producing an instantaneous sharp pain
      that causes him to fall to his knees involuntarily to alleviate the pressure. The
      exact etiology of the pain elicited by this technique has been obscure to many
      practitioners. The usual explanations have been nerve compression, joint capsular
      stretch, tendon/muscle strain, or partial ligamentous disruption. Studies of a
      cadaver's wrist have shown that Nikyo forcibly compresses the pisiform bone
      against the ulna, two bones that do not normally articulate. The intense pain
      thereby produced results from stimulation of the periosteal nerves in these bony
      surfaces.

PMID- 8284143
TI  - The EEG in the determination of fitness to fly.
AB  - Previous studies have shown a low incidence of clinical seizure development in
      healthy individuals with EEG epileptiform discharge activity. This has tended to
      de-emphasise the role of the EEG in screening pilots. A call is made for
      consideration of impairment of function associated with epileptiform discharges
      as a relevant factor in determination of fitness to fly and reconsideration of
      the role of the EEG in this area.

PMID- 8284144
TI  - Body-image distortion and mental imagery.
AB  - This study explored whether body-image distortion is a function of difficulties
      with imagery or problems with judgment. 49 subjects were given the Modified Video
      Camera Technique to measure body-image distortion. Mental imagery was measured by
      a modified version of the Vividness of Visual Imagery Questionnaire and the
      Spatial Relations subtest of the Woodcock-Johnson Psycho-educational Battery.
      Visual recall was assessed on the Meier Art Judgment Test. Judgment bias was
      assessed by the Stunkard Silhouette Method and the shape and weight subscales of
      the Eating Disorder Examination. Subjects who distorted body-image scored
      significantly more poorly on mental imagery than those who did not distort. No
      differences were found between groups on visual memory recall or in judgment
      bias.

PMID- 8284145
TI  - An analysis of sidedness in traditional Goju-ryu karate kata.
AB  - The 684 moves of the 12 Goju-ryu kata (forms) widely practised today were
      analysed for left-right bias. Significant right-sided bias was evident for kicks
      only.

PMID- 8284146
TI  - Color-naming and color-matching by preschool children as a function of visual
      field and sex.
AB  - The accuracy for both a color-naming and a color-matching task as a function of
      visual field and sex was investigated in preschool children. Subjects were 17
      boys and 17 girls ranging in age from 4.4 to 5.6 yr. Each subject was tested on
      both tasks, for which the target stimuli were presented tachistoscopically.
      Accuracy measures for each task were obtained separately for both left and right
      visual fields. A two-factor (sex x visual field) analysis of variance with
      repeated measures on the visual-field factor showed a significant difference
      between the sexes on the color-naming task only. No significant difference
      between visual fields was found for either task. However, significant
      interactions between sex and visual field for both the color-naming and color
      matching tasks were obtained. t tests for simple main effects showed a
      significant right visual-field advantage for girls in naming colors. Conversely,
      a significant left visual-field advantage for color-matching was found for boys.
      Also, on the color-matching task, significant sex differences were found for both
      visual fields when compared separately. Boys were more accurate for left and
      girls more accurate for right visual field. Boys performed in a more strongly
      lateralized fashion on the color-matching task than did the girls, supporting the
      notion of greater lateralization among males.

PMID- 8284147
TI  - A memory advantage for serial lists composed of active words.
AB  - Results from subject-wise and word-wise analyses of recall for four types of
      emotional lists memorized by 14 subjects confirm that active words (pleasant and
      active, unpleasant and active) are better recalled than passive words (pleasant
      and passive, unpleasant and passive). The standardized formula 'recall = .68
      (serial position) + .24 (activation)' successfully predicts 53% (R = .73) of
      variance in the recall criterion.

PMID- 8284148
TI  - Reinforcement generalization as interaction between processes rather than events:
      absence of schedule-induced hyperdipsia in rats with histories of minimal food
      water contiguity.
AB  - All scientific disciplines contain concepts that reflect interactions between
      their processes as well as between their units. The divergence process
      (generalization) applied to reinforcement predicts the existence of reinforcement
      generalization. Existence of this operation was suggested by the absence of
      schedule-induced hyperdipsia in rats for which the normal temporal contiguity
      between eating and drinking had been prevented. The results indicate that through
      generalization of reinforcement, which could explain the adjunctive class of
      behaviors, reinforcement of one process evokes comparable changes in other
      processes even if their overt correlates are not displayed contiguously.

PMID- 8284149
TI  - Live-social-video reward maintains joystick task performance in bonnet macaques.
AB  - A number of studies have now indicated that monkeys of several species will
      perform hundreds of food-rewarded joystick tasks on a daily basis. Our goal in
      this study was to identify the level of joystick task performance that could be
      maintained by 10 sec. of live, color video of a conspecific social group
      contingent upon the completion of a joystick task. The subjects were five
      individually housed bonnet macaques that were highly experienced on joystick
      tasks. Performance with social-video reward was compared to that maintained by a
      190-mg banana-flavored pellet reward and to a nonreward condition. Comparable
      levels of task activity were maintained by both video and pellet reward, whereas
      task activity nearly ceased in the absence of reward. Four of the five monkeys
      increased their levels of task activity between the first and second weeks of
      social-video reward.

PMID- 8284150
TI  - Perceived control, adjustment, and communication problems in laryngeal cancer
      survivors.
AB  - Health locus of control, adjustment to cancer, and communication experiences
      after a laryngectomy were investigated in 63 laryngeal cancer survivors.
      Survivors who showed internal control also scored as better adjusted and had
      fewer communication problems. Scales were intercorrelated (.68 to .92).

PMID- 8284151
TI  - Beta-endorphin response to endurance exercise: relationship to exercise
      dependence.
AB  - Considerable research has shown significant increases in beta-endorphin levels
      after aerobic activity. These increases and their accompanying euphoric effect
      have been suggested as a possible psychophysiological mechanism underlying the
      exercise-dependence syndrome. The relationship between plasma beta-endorphin
      levels and a tendency towards exercise dependence, however, has not been
      established. To examine this relationship, 8 women trained in aerobic dance
      completed an exercise-dependence assessment prior to participation in a 45-min.
      session of continuous aerobic dance. Plasma beta-endorphin concentration was
      measured both prior to and following the aerobics routine. A Student t test for
      paired observations indicated that mean plasma beta-endorphin levels (+/- SE)
      were significantly higher after the aerobics routine (11.96 +/- 1.3 pg beta-EP.ml
      1) than preexercise levels (8.62 +/- 1.4). However, beta-endorphin difference
      values (% change) were not significantly correlated with scores on the exercise
      dependence survey. Those data suggest that scores on exercise dependence are not
      related to changes in plasma beta-endorphin levels after aerobic exercise.

PMID- 8284152
TI  - Changes in construals of tic-producing situations following cognitive and
      behavioral therapy.
AB  - 12 clients suffering from chronic tics participated in one of two treatment
      programs, either a behavioral group using competing response therapy or a group
      using Beck-style cognitive restructuring. A repertory grid based upon the
      personal construct psychology of George Kelly was administered to all clients
      before and after treatment. The grid comprised a set of elements made up of
      situations with high, medium, and low risk of eliciting tics, and constructs were
      derived from comparisons between them. Clients' ratings of the elements on the
      constructs were subjected to a principal components analysis using an INGRID
      program. Following treatment the total variation around construct means decreased
      in both groups but significantly more in the cognitive group, indicating a
      narrowing of the difference in their perceptions of situations which formerly
      indicated high and low risk of inducing tics.

PMID- 8284153
TI  - Pavlovian conditioning of the tickle response of human subjects: temporal and
      delay conditioning.
AB  - Previous studies of the human response to a tickle have demonstrated that
      subjects will respond to a gesture that signals the onset of a tickle in the same
      way as to a tickle. Researchers have described this anticipatory response as an
      "expectation." In the current study, we investigated, from the Pavlovian
      framework, the response to a verbal stimulus preceding the tickle stimulus. We
      exposed subjects to experimental phases which included the Neutral Stimulus
      Alone, 100% Pairing of the Neutral and Unconditioned Stimuli (tickle strokes to
      the foot), Random Presentation, Partial (75%) Reinforcement, and Temporal
      Conditioning. Pavlovian conditioning was observed in all phases, suggesting a
      parsimonious explanation for the expectation effect described by others.

PMID- 8284154
TI  - Using self-recording of on-task behavior by a preschool child with disabilities.
AB  - In an evaluation of effects of self-monitoring on the on-task behavior by a
      preschool child with disabilities, analysis indicated that self-monitoring
      increased the child's on-task behavior in each of three settings in the
      classroom. The import of these findings for preschool education was noted.

PMID- 8284155
TI  - Field dependence-independence and brain organization: the confluence of two
      different ways of describing general forms of cognitive functioning? A
      theoretical review.
AB  - We reviewed a total of 67 studies of the relationship between the cognitive style
      dimension of field dependence-independence and brain organization. To date, such
      studies have followed three basic lines of approach: (1) cerebral localization of
      processes involved in field dependence-independence; (2) evaluation of the
      relationship between field dependence-independence and hemisphericity; (3)
      evaluation of the relationship between field dependence-independence and
      hemispheric differentiation. The results of all three types of study are largely
      coherent with the differentiation theory formulated by Witkin and his coworkers.
      In addition, findings to date are of interest in that they suggest new directions
      for more detailed investigation of the relationship between field dependence
      independence and brain organization. These directions appear very promising for
      improving our understanding of both the nature of cognitive styles and the
      functioning of the brain in general.

PMID- 8284156
TI  - One explanatory basis for the discrepancy of reported prevalences of sleep
      paralysis among healthy respondents.
AB  - In a previous study, the author and coworkers found 39.8% of healthy young adults
      had experienced sleep paralysis. Some other studies reported prevalence as about
      the same or higher (i.e., 40.7% to 62.0%) than that previous estimate, while yet
      other studies, including Goode's work cited by ASDC and ASDA classifications,
      suggested much lower prevalences (i.e., 4.7% to 26.2%). The author tested the
      hypothesis that this discrepancy among the reported prevalences is partly due to
      the expression used in each questionnaire. University students who answered the
      questionnaire using the term 'transient paralysis' reported the lower prevalence
      (26.4%), while the second group of respondents who answered the questionnaire
      using the term kanashibari, the Japanese folklore expression for sleep paralysis,
      gave the higher prevalence (39.3%). The third group who answered the
      questionnaire with the term 'condition,' probably a rather neutral expression,
      marked the middle (31.0%) of these.

PMID- 8284157
TI  - Adolescent time perspective: a further note.
AB  - Researchers on temporal extension have moved from using global measures of
      temporal extension to using domain-specific measures. A reanalysis of 1992 data
      from 98 boys and 103 girls tested whether domain-specific measures of temporal
      extension were correlated with global measures of both past and future temporal
      extension. Moderate correlations support the generalisation of findings from
      earlier studies, using global measures, to more recent studies with domain
      specific measures.

PMID- 8284158
TI  - Effect of preference for rock music on magnitude-production scaling behavior in
      young adults: a validation.
AB  - The purpose of the presence study was to examine the effect of preference for
      rock music on magnitude-production scaling behavior in young adults as an attempt
      to validate further the 1993 magnitude-estimation scaling results obtained by
      Fucci, Harris, Petrosino, and Banks. Two groups of young adults, 20 who liked
      rock music and 20 who disliked rock music, were tested. Subjects were instructed
      to adjust the intensity of a 10-sec. sample of rock music in response to seven
      written stimuli presented in random order. Analysis indicated that there was a
      significant difference in performance by the two groups of subjects on the
      magnitude-production scaling task. Those subjects who liked rock music adjusted
      the intensity of the music to higher levels than did the subjects who disliked
      rock music.

PMID- 8284159
TI  - Personal values in sport of visually impaired and sighted wrestlers.
AB  - This investigation compared the priority given to 14 sport-related values by 11
      wrestlers with normal sight and 11 with visual impairments. The Survey of Values
      in Sport was given to 22 high school wrestlers during the competitive season.
      Independent t tests were used to evaluate differences in priority of values
      between the two groups. Significant differences were found on cooperation, group
      coordination, being a good sport, and being in a good place, which wrestlers with
      visual impairments valued higher in priority than the wrestlers with normal
      sight.

PMID- 8284160
TI  - Lateral preference of preschool and primary school children.
AB  - Cross-sectional development and consistency of four lateral preference behaviors
      (hand, foot, ear, eye) in 79 preschool and 131 primary school children were
      studied. Although predominant right-sidedness is manifested in the limbs and
      sensory organs, only handedness showed a significant increase over the age range
      studied (3 yr. to 9 yr., 11 mo.). Approximately 85% of children in preschool and
      87% in primary school showed lateral consistency in the upper and lower
      extremities. The concordance between other sidedness behaviors reflected only
      chance associations in both samples. The results indicate that lateral preference
      behaviors in children are not unidimensional.

PMID- 8284161
TI  - Karate for self-defense: an analysis of Goju-ryu and Kyokushinkai kata.
AB  - 12 Goju-ryu and 24 Kyokushinkai kata (forms) widely practised today were analysed
      for blocking and counter-offensive techniques. A statistically significant
      preference was found for blocking in Goju-ryu kata and a significant preference
      for counter-offensive techniques in Kyokushinkai kata. The kata from both styles
      were seen as fostering nonviolence in their practitioners, however.

PMID- 8284162
TI  - Hemisphericity style, sex, and performance on a letter-detection task.
AB  - Subjects classified by scores on the Preference Questionnaire as preferring
      either a left- or a right-hemisphericity style were asked to read a one-page
      passage and to circle each letter t they encountered as they read the passage.
      There were no statistically significant differences in letter detection between
      the 58 right- and the 64 left-style scorers. However, contrary to previous
      findings, the 73 women detected significantly more ts, including unsounded ts,
      than the 55 men. Our results suggest that hemisphericity style is not an
      important factor in letter detection.

PMID- 8284163
TI  - Differences in dynamic visual acuity between athletes and nonathletes.
AB  - We surveyed the dynamic visual acuity of 53 university athletes and 46 nonathlete
      university students, using a Landolt C ring as a target. The target moved from
      left to right on screen initially at the maximum angular velocity of 300
      degrees/sec. and then gradually decreased in velocity until the subject
      recognized the direction of the gap in the Landolt C ring. The angular velocities
      at which the subject correctly recognized the direction of the gap were used as
      the parameters of the acuity measure. When the sizes of the gap in the Landolt C
      ring were 42' and 28', there were no differences in the performances of the
      athletes and nonathletes. However, when the gap sizes were 14' and 8', athletes
      could recognize the gap at significantly higher velocities than the nonathletes.
      In this case the dynamic visual acuity of athletes was superior to that of the
      nonathletes.

PMID- 8284164
TI  - Perceived parents' support for learning and aspirations for Australian
      adolescents.
AB  - Relationships were examined between perceptions of parents' support for learning
      and measures of aspirations for Australian adolescents from different ethnic
      groups. The findings indicated that perceptions of parents' support combined to
      have significant associations with aspirations but there were ethnic-group
      differences in how adolescents' perceptions of fathers' and mothers' support were
      related to their aspirations.

PMID- 8284165
TI  - The role of vision in sound localization.
AB  - Three experiments examined the role of vision in locating a brief sound (2-sec.
      speech noise) from an unseen source in the horizontal left front quadrant. The
      head could be freely moved. Subjects could point to the sound location more
      accurately with eyes open. However, since in a second study the accuracy of
      pointing a finger was poorer than for aiming one's eyes at the sound, the effect
      in the first study may reflect using vision to calibrate the hand location. A
      third study showed no difference in accuracy of aiming one's eyes at a sound when
      eyes were open versus closed during presentation of sound. More accurate auditory
      localization with eyes open than closed was not supported.

PMID- 8284166
TI  - Relationship between body image and percent body fat among college male varsity
      athletes and nonathletes.
AB  - Three groups of students from a large midwestern university (15 varsity swimmers,
      15 varsity football players, and 15 nonathletes) were administered a 20-item
      questionnaire concerned with body image and subsequently underwent skinfold
      measurements to assess percent body fat. Scores obtained were correlated to
      estimate the relationship between body image and adiposity. For the groups
      combined (N = 45) the relationship was significant and inverse (r = -0.51). For
      the nonathletic group a significant value -0.76 was found; for the two groups of
      athletes there was no relationship (rs = 0.002 and -0.059 for football players
      and swimmers, respectively). We conclude that body image as measured in this
      study in inversely related to percent body fat among college men, especially
      among students not engaged in varsity sports.

PMID- 8284167
TI  - Evaluation of the influence of illiteracy on neuropsychological performances by
      elderly persons.
AB  - The aim of the present study was to verify the role of the primary notions
      acquired in early school in the formation of a general strategy in elaboration of
      information. For this purpose we selected a tiny rural village in southern Italy
      which comprises a substantial number of elderly persons having very little formal
      schooling. These subjects were screened using a test battery composed of classic
      neuropsychological tests and reaction-time tests. In the subjects studied we
      observed a significant correlation between the amount of education and the
      neuropsychological performances, although no such correlation existed for
      reaction times. Subjects having little schooling (up to 3 years) performed better
      than the illiterate persons on the Constructional Apraxia test and on the Raven
      Matrices. However, the reaction times were similar in these groups. On this basis
      we claim that reaction-time tests might form a basic tool in evaluating cognitive
      performances of persons with very little schooling. Further, the primary notions
      learned during the first few years of schooling induce an improvement in mental
      strategies that is well-preserved in the normal aging process.

PMID- 8284168
TI  - Visual search in simple simulations of realistic scenes.
AB  - The effect distracting objects have on visual-search performance in real-life
      situations cannot readily be predicted from current search theories. The validity
      of an approach to close this gap was tested by comparing search performance for
      color slides of scenes in public buildings with performance for simplified
      computer-generated images derived from these slides. The target was always a blue
      rectangle in both the original slides of scenes and the computer simulations. The
      distractors were differently colored rectangles (not blue), and their number was
      varied systematically. Analysis showed a significant linear increase in search
      time with number of distractors, which challenges predictions of current search
      theories. An explanation for this contradiction is proposed. Also, search times
      for color slides were significantly longer than those for computer images;
      however, there was no significant interaction between type of stimulus and number
      of distractors. It is concluded that the simulated scenes yielded adequate
      predictions of the effect of distracting objects on search performance in real
      life situations.

PMID- 8284169
TI  - Reliability of judging genuine and simulated suicide notes.

PMID- 8284170
TI  - The sugar scoring system for the Bender-Gestalt test: an objective approach that
      reflects clinical judgment.
AB  - Although several objective scoring systems have been developed for use with the
      abbreviated form of the Bender-Gestalt test of visuomotor development (Figures A,
      1, 2, 4, 6, and 8), each has been criticized as being inadequate in some way or
      other. This paper reviews the inadequacies of these systems as described in the
      literature and presents the results of a small study designed to investigate the
      psychometric properties of a new objective scoring system, recently proposed by
      Sugar, which incorporates both quantitative and qualitative perspectives. The new
      system is shown to be psychometrically sound in validity and reliability.
      Additional advantages are described. The new system is recommended as a good, if
      not better, alternative to other, existing methods for scoring the Bender-Gestalt
      test.

PMID- 8284171
TI  - Developmental outcome of very low birth weight infants with intraventricular
      hemorrhage.

PMID- 8284172
TI  - Intensity of amnesia during hypnosis is positively correlated with estimated
      prevalence of sexual abuse and alien abductions: implications for the false
      memory syndrome.
AB  - 20 normal young women listened to an ambiguous story concerning a young boy who
      experienced fear, odd smells, and a smothering sensation during the night and
      skin lesions the next morning. After the Hypnotic Induction Profile (HIP) had
      been established, they were asked to estimate either the percentage prevalence of
      childhood sexual abuse or alien abduction in the general population. There were
      moderate (0.50) positive correlations between the subjects' estimates of
      prevalence and the amount of amnesia ("lost time") and indices of right
      hemispheric anomalies (history of sensed presence and left-ear suppressions
      during a dichotic-listening task). Relevance of observations to formation of the
      False Memory Syndrome and to the development of nonpsychotic delusions is
      discussed.

PMID- 8284173
TI  - Effects of subliminal stimuli on unconscious processing of anxiety: an
      examination of implicit perception.
AB  - Researchers in cognitive psychology generally accept that information, including
      emotions, may be processed outside of awareness. Some have postulated that
      anxiety may be induced by stimuli presented below the level of detection, a
      process called implicit perception; however, conflicting findings as to the
      validity of subliminal stimuli in influencing anxiety have been reported over the
      past decade. In the present study, 39 subjects were exposed to either positive,
      negative, or neutral subliminal stimuli, and half the subjects were informed as
      to the type of stimuli they received. All subjects were monitored for frontalis
      muscle tension, a physiological indicator of anxiety, on an electromyograph
      (EMG). No significant effects of the exposure upon EMG recordings were noted.
      Awareness of the type of stimuli presented had a small but insignificant effect.
      These results, although tentative, when replicated would question the validity of
      subliminal visual presentation in altering emotive states.

PMID- 8284174
TI  - The age-range illusion in developmental research on the structure of abilities: a
      comment on Lis and Magro.
AB  - The general effect of age range on findings from studies of the structure of
      intellectual abilities in children is considered. Two topical examples of the
      effect in the work of Lis and Magro and that of Demetriou and Efklides are
      considered.

PMID- 8284175
TI  - Effects of self-modeling on self-efficacy and balance beam performance.
AB  - The purpose of this investigation was to assess the effect of self-modeling on
      self-efficacy and performance of balance beam routines. Subjects were
      intermediate-level female gymnasts who were randomly assigned to one of two
      groups, a self-modeling or a control group. For the self-modeling group, self
      modeling videotapes were made of each subject performing her balance beam
      routine. During a 6-wk. period, self-modeling group subjects viewed the videotape
      of themselves three times a week prior to practice. During this time, the control
      group and self-modeling group participated in their normal instructional program.
      All subjects completed self-efficacy inventories and balance beam skill tests at
      four intervals, a pretest, a 2-wk. test, a 4-wk. test, and a 6-wk. posttest.
      Although no significant differences in ratings of self-efficacy or balance beam
      performance between the groups were found, the correlation between subjects' self
      rated performance scores and actual performance scores for the self-modeling
      group was significant (r = .92). This correlation was not significant for the
      control group (r = .02). This significant correlation suggests that self-modeling
      may enhance performers' ability to assess their own performance realistically,
      improving their understanding and use of instructional feedback to enhance
      performance.

PMID- 8284176
TI  - Acoustic analysis of diplophonia: a follow-up report.
AB  - Additional information on the physiology of the diplophonic speech produced by an
      adult female is provided. Direct endoscopic examination of the subject's
      laryngeal mechanism showed her diplophonia was produced by exerting differential
      tension on her vocal folds. The ventricular folds were not directly involved.

PMID- 8284177
TI  - Random-number generation and the menstrual cycle: preliminary evidence for a
      premenstrual alteration of frontal lobe functioning.
AB  - 20 women (M age = 30.4 yr.) were given the "Mental Dice Task" (randomization of
      the numbers from 1 to 6) once during the preovulatory and once during the
      premenstrual phases of their menstrual cycles. In addition, for both test
      sessions a premenstrual-symptom score was assessed reflecting self-rated severity
      of cognitive, affective, and somatic complaints during the preovular and the
      premenstrual phases. In comparison to series of real dice throws, the Mental Dice
      sequences of all the subjects showed a relative lack of repetitions and an excess
      of counting at both times of testing. Counting bias was significantly enhanced in
      the sequences generated during the premenstrual testing and the size of this bias
      was positively correlated with the self-rated severity of premenstrual symptoms.
      Pronounced counting despite the instruction to randomize was interpreted as
      reflecting decreased ability to suppress task-irrelevant cues and indicating a
      relative impairment of frontal lobe functioning. Resistance of the Mental Dice
      Task towards expectation biases renders a sociopsychological interpretation of
      these results improbable. We conjecture that, like other cognitive processes,
      frontal lobe functions also fluctuate with hormonal changes.

PMID- 8284178
TI  - Domestic integration and suicide in England and Wales, 1901-1975.

PMID- 8284179
TI  - Vividness of imagery and creativity.
AB  - We evaluated the extent to which vividness of imagery is correlated with
      creativity in a sample of 1361 university students from different disciplines and
      assessed which sensory modalities of vividness of imagery best predicted
      creativity. Vividness of imagery was generally poorly correlated with creativity
      and, for all subjects combined, explained only about 2% of total variance in
      creativity. Promising directions for research are mentioned.

PMID- 8284180
TI  - Television viewing and exercise habits of 8,885 adults.

PMID- 8284181
TI  - Gender differences in motor performance of 50- to 79-year-old adults.
AB  - This study was conducted to assess gender and age differences among 73 men and
      women (50-59, 60-69, and 70-79 yr.) on five motor tasks (balance, standing long
      jump, sit and reach, hand grip, and softball throw). Differences between men and
      women on the standing long jump, hand grip, and the softball throw favored men.
      The men had better performance scores than the women on each of these tasks. An
      interaction of gender by age was noted on the balance task. Women 50-59 yr. old
      balanced significantly longer than the men of that age group. Age differences
      were found for the standing long jump, hand grip, and softball throw. The 50-59
      age group performed significantly better than the 60-69 and the 70-79 age groups.
      Performance decreased on each task across age groups. These findings suggest
      gender differences in motor performance of older adults as has been noted for
      children.

PMID- 8284182
TI  - Preliminary study of the bilingual version of the Khatena-Torrance Creative
      Perception Inventory.
AB  - A bilingual version of the Khatena-Torrance Creative Perception Inventory was
      given to 70 Malaysian students. The two 50-item subscales, 'Something About
      Myself' and 'What Kind of Person Are You?", require the respondent to choose one
      of two alternatives. Test-retest reliability and criterion validity indices for
      this version suggest the bilingual form is suitable to assess the creative
      perception of these students. Replication with other groups is recommended.

PMID- 8284183
TI  - Performance of subjects with probable Alzheimer disease and normal elderly
      controls on the Gollin Incomplete Pictures Test.
AB  - Our study was designed to evaluate perceptual ability measured by the Gollin
      Incomplete Pictures Test (in which subjects identify fragmented pictures of
      common objects) in Alzheimer Disease. We developed a standardized procedure for
      administering Gollin's test and compared the performance of 58 Alzheimer patients
      and 37 elderly controls on the Gollin, two design copying tests, the Mini-Mental
      State Examination, a verbal version of the Knox Cubes test, a recognition memory
      test, and a verbal fluency test. Alzheimer patients performed significantly more
      poorly than controls on all tests. Factor analysis demonstrated a visual
      perceptual factor, with loadings on the Gollin test and design copying, and three
      other factors representing primary memory, secondary memory, and language.
      Results indicate the Gollin test measures visual perceptual ability, but the
      precise nature of the task requires further study. Identification of fragmented
      pictures appears a practical and potentially useful measure for evaluating at
      least some aspects of visual perception in patients with generalized cognitive
      impairment.

PMID- 8284184
TI  - Anarthria impairs subvocal counting.
AB  - We studied subvocal counting in two pure anarthric patients. Analysis showed that
      they performed definitively worse than normal subjects free to articulate
      subvocally and their scores were in the lower bounds of the performances of
      subjects suppressing articulation. These results suggest that subvocal counting
      is impaired after anarthria.

PMID- 8284186
TI  - Relational communication messages of type-A scoring physicians.

PMID- 8284185
TI  - Psychology of computer use: XXX. Effects of presentation speed on pupil size
      using negative and positive CRTS.
AB  - The effects of presentation speed and both positive and negative CRT (cathode ray
      tube) displays on pupil size were studied. The pupillary areas of 12 female
      student volunteers were measured by infrared videopupillography. The three
      presentation speeds were no change for 12 sec., a change every 2 sec. for 12
      sec., and a change every 1/2 sec. for 12 sec. Two-way analysis of variance showed
      that the pupil size in the negative displays was significantly larger than that
      in the positive displays. A difference in pupillary area results from different
      display speeds, irrespective of a difference in polarity.

PMID- 8284187
TI  - A subjective index of American social, economic, and political threat, war and
      personal violence.

PMID- 8284188
TI  - Interactive effects of musical and visual cues on time perception: an application
      to waiting lines in banks.
AB  - This study explores the interactive effects of musical and visual cues on time
      perception in a specific situation, that of waiting in a bank. Videotapes are
      employed to stimulate the situation; a 2 x 3 factorial design (N = 427) is used:
      2 (high vs low) amounts of visual information and 2 (fast vs slow) levels of
      musical tempo in addition to a no-music condition. Two mediating variables are
      tested in the relation between the independent variables (musical and visual
      ones) and the dependent variable (perceived waiting time), mood and attention.
      Results of multivariate analysis of variance and a system of simultaneous
      equations show that musical cues and visual cues have no symmetrical effects: the
      musical tempo has a global (moderating) effect on the whole structure of the
      relations between dependent, independent, and mediating variables but has no
      direct influence on time perception. The visual cues affect time perception, the
      significance of which depends on musical tempo. Also, the "Resource Allocation
      Model of Time Estimation" predicts the attention-time relation better than
      Ornstein's "storage-size theory." Mood state serves as a substitute for time
      information with slow music, but its effects are cancelled with fast music.

PMID- 8284189
TI  - [Evaluation of lumbar vertebral bone marrow changes with MR imaging].
AB  - Seven hundred nine magnetic resonance (MR) imaging studies of the lumbar spine
      were reviewed to assess the signal intensity (SI) changes in vertebral bone
      marrow. Marrow changes were classified into four types according to their SI
      changes on T 1-weighted images (T 1-WI) and T 2-WI. Type 1 changes (decreased SI
      on T 1-WI and increased SI on T 2-WI) were identified in 28 patients (3.9%), type
      2 changes (increased SI on T 1-WI and isointense or slightly increased SI on T 2
      WI) in 184 (26%), type 3 changes (decreased SI on both T 1-, T 2-WI) in 71 (10%),
      and type 4 changes (linearly increased SI on T 1-WI in the center of the
      vertebral body) in 142 (20%). Plain radiographs showed sclerotic changes in
      patients with type 3. In patients with type 1 or 4 changes, no focal
      abnormalities were observed. Histological evaluation of type 1 change revealed
      fibrous tissue including cartilaginous formation. Focal replacement by fatty
      tissue was observed in type 2 and type 4 changes. Bone sclerosis was observed in
      type 4 change. Type 1, type 2 and type 3 changes, which occurred commonly in the
      old and in the lower lumbar levels, appear to reflect a spectrum of degenerative
      changes of the bone marrow including both pathological and physiological ones.

PMID- 8284190
TI  - [Intravascular ultrasound imaging as adjunct to vascular interventions:
      preliminary experience in patients with atherosclerotic disease].
AB  - Catheter-based intravascular ultrasound (IVUS) imaging is new, evolving technique
      in which a high-frequency transducer is attached to the tip of a catheter. In
      this study, we evaluated the usefulness of catheter-based IVUS in 11 patients
      with atherosclerotic disease as an adjunct to PTA or atherectomy. A 30-MHz
      ultrasound catheter was inserted through a 6 F sheath to obtain real-time and
      cross-sectional images. The IVUS images demonstrated a three-layered appearance
      of muscular arteries, intimal thickening and calcification. IVUS was performed in
      11 patients undergoing percutaneous transluminal angioplasty (7 patients) or
      atherectomy (4 patients). The presence of dissection between the media and
      atheroma was observed after balloon angioplasty, while IVUS imaging demonstrated
      a smooth wall after atherectomy. There was a good correlation between IVUS and
      angiography in the quantitative assessment of luminal %diameter stenosis before
      vascular intervention, but a poor correlation was observed after angioplasty,
      probably due to the dissections from balloon dilatation that resulted in
      irregular crescentic pathways with unclear borders to the lumen on angiography.
      The results of our study illustrate the potential utility of IVUS as an adjunct
      to transluminal vascular intervention.

PMID- 8284191
TI  - [The evaluation of lung cancers hidden by the mediastinal and hilar shadows on
      the plain chest film].
AB  - We retrospectively evaluated the plain chest frontal radiographs in four cases in
      which the lung cancers were quite difficult to observe prospectively on plain
      chest frontal radiographs in spite of the relatively large size of tumors (over 3
      cm in diameter). Three of four cases were central-type lung cancers, two squamous
      cell carcinomas and one adenosquamous cell carcinoma. Since there was no
      associated atelectasis or obstructive pneumonia in these cases, wall thickening
      and indistinctness of the lumen of the central bronchi were the significant
      findings for diagnosis. One case proven to be adenocarcinoma was located in the
      periphery of S6. A focally increased radiopacity behind the descending pulmonary
      artery was the only finding to pointed out. Since tumors were not demonstrated
      directly in the aerated lungs, the condition of the central bronchi as well as
      the degree radiopacity of the pulmonary artery should be carefully interpreted.

PMID- 8284192
TI  - [An improved method of preparation of autopsied human inflated-fixed whole lungs
      for radiologic-pathologic correlation].
AB  - Inflated-fixed lung specimens, prepared using polyethyleneglycol 400, the
      standard Heitzman method have the disadvantage of bad staining. The authors
      attempted to improve this short-coming using human autopsied lungs and evaluated
      both microscopical findings and the degree of specimen inflation. Fifty-five
      human autopsied whole lungs were examined. Forty-six lungs with cannulation
      through the main bronchus were distended with 20% formalin, after clamping the
      cannula for 15 minutes to six days, formalin in lungs was expelled by air at 10
      cm H2O pressure, then fixed with fixative-fluid containing polyethyleneglycol
      400, 95% ethyl-alcohol, 40% formalin and water mixed in a ratio of 10:5:2:3. In 9
      lungs without cannulation, formalin was expelled manually. The degree of
      distension of 46 of the 55 cannulated specimens was satisfactory (score A: 42
      specimens, score B: 4 specimens). In 9 specimens without cannulation, inflation
      was poor (Score C). Good or excellent staining was obtained in 29 specimens
      (Score A: 10 specimens, Score B: 19 specimens), but 3 specimens were not be
      improved (Score C). Both inflation and staining were good in 21 specimens. This
      new method, requiring cannulation in the main bronchus, inflated-fixation with
      20% formalin and expulsion of formalin by air prior to the standard Heitzman
      method enables both high quality staining and radiographs of the inflated-fixed
      lung specimen.

PMID- 8284193
TI  - [MR evaluation of common femoral arterial flow: age-related changes and
      characteristics in obstructive arterial disease of lower extremities].
AB  - Flow velocity measurements of the common femoral arteries in 60 lower extremities
      of 30 healthy subjects and 12 lower extremities of 7 patients with
      arteriosclerosis obliterans (ASO) were performed by means of magnetic resonance
      imaging with a use of presaturation bolus tracking (PBT) method. Our PBT method
      can provide both precise determination of flow velocity and evaluation of flow
      patterns within 30 minutes in the clinical setting. In phantom study, MR flow
      velocity had good correlation with actual flow velocity (r = 0.997). 30 healthy
      volunteers were classified into three groups; group I (20-40 years), group II (41
      60 years) and group III (61-80 years). Starting time of acceleration (STA) were
      shortened as the age progressed. Peak reverse velocity (PRV), maximum
      deceleration rate (MDR), peak forward velocity/mean velocity ratio (PFV/MV) and
      pulsatility index (PI) were significantly decreased in group III as compared to
      group I and group II. Although intraluminal flow profile showed almost uniform
      during acceleration time on MR images, flow profile became disproportioned and
      reverse flow was observed in the medial portion during deceleration time. These
      characteristic hemodynamics were recognized in all healthy subjects regardless to
      the different age group. In ASO, STA was prolonged and PFV, PRV, Maximum
      acceleration rate, MDR, PFV/MV, PI, Vascular sectional area, flow volume were
      significantly decreased (p < 0.001) as compared to the control healthy group III.
      As the result we obtained marked characteristics such as flattening of curves and
      disappearance of reverse flow in MR flow waveform. On MR images, disproportion of
      intraluminal flow profile, decreased flow velocities during acceleration time and
      disappearance of reverse flow (11 of 12 extremities) during deceleration time
      were observed.

PMID- 8284194
TI  - [The consideration and performing of pretesting of contrast medium: surveying in
      Kanagawa].
AB  - The pretesting of contrast medium is world widely recognized to be an invaluable
      method to predict the adverse reactions. It was still required to perform on
      patients who shall have a contrast examination until recently in Japan. In May of
      1990 the contrast drug package insert was reviewed and a statement of "there is
      no known method to predict the adverse reactions" was included. Although two
      reports suggested that the percentage of not performing the pretesting was
      increasing gradually since then, the clinical communications between institutes
      did not support the truth. This study investigated the problem by surveying the
      area in Kanagawa-ken neighboring to Tokyo and revealed that: 1. The percentage of
      non-performing the pretesting is high in radiologist and urologist (both are 40%)
      but low in other physicians (18%). 2. The risky performances of pretesting in the
      area without emergent equipment are occurring daily. 3. The percentage of the
      approval to abandon the pretesting increased significantly (from 46% to 89% with
      p < 0.01) after the accurate information on pretesting was given. 4. To prevent
      the tragedy caused by risky performance, actively contacting with and offering
      the information are necessary.

PMID- 8284195
TI  - [Development of oral reporting system in PACS environment].
AB  - An experimental radiologic reporting system using oral presentations has been
      developed and tested. The rewritable and compact magneto-optical disk (MOD) is
      employed to store oral diagnostic reports together with read radiologic images.
      The MOD is 5.25 inches in diameter, has a 600 MB memory capacity, and is
      erasable, light and compact. Advantages of the system are simultaneous retrieval
      of oral reports by a radiologist and the images he or she interpreted, and the
      capability of media circulation in addition to the function of filing. Thus MOD
      has a multimedia function of both off-line communication and filing. When medical
      images are interpreted and oral presentations are registered, automatically
      digitized oral reports and digitized images are filed in the MOD. Referring
      physicians can get oral diagnostic reports and can see the images at the same
      time on a personal computer. Furthermore, integration with voice recognition
      capability is being tried in our experiment.

PMID- 8284196
TI  - [Clinical evaluation of ultrasonic measurement of the calcaneal bone].
AB  - We measured the speed of sound (SOS) and broadband ultrasound attenuation (BUA)
      in the calcaneal bone and compared those values with bone mineral density (BMD)
      as assessed by single X-ray absorptiometry and dual energy X-ray absorptiometry.
      Calcaneal speed of sound and broad band ultrasound attenuation showed an earlier
      decrease with age than lumbar BMD, Calcaneal SOS and BUA correlated well with
      calcaneal BMD. Calcaneal SOS correlated more closely with neck BMD than lumbar
      BMD measured by DXA. Furthermore, measurement of calcaneal SOS is more useful
      than measurement of lumbar BMD to evaluate femoral neck BMD, which might be very
      important for clinical purposes. Both body weight and height correlated well with
      calcaneal BMD but not so well with calcaneal SOS or BUA. As ultrasound emits no
      radiation, we can use it without the restriction of radiation protection.

PMID- 8284198
TI  - Isolation and cloning of putative mouse DNA replication initiation sites: binding
      to nuclear protein factors.
AB  - By using an original two-step technique (trioxsalen
      crosslinking/immunoprecipitation) we were able to isolate in a single-stranded
      form a fraction of mouse DNA enriched in putative Replication Initiation
      Sequences (RIS). The isolated and purified single-strand fragments were made
      double-stranded in vitro and were cloned in pUC12 to prepare a confined RIS
      library. 30 randomly selected RIS inserts were subjected to gel mobility shift
      assay using nuclear extracts either from dividing, or from quiescent mouse cells.
      Twelve out of the 30 RIS fragments showed specific binding to proteins present in
      nuclear extract from dividing cells, while none were retarded by extracts from
      quiescent cells. RIS12, RIS18 and RIS30 were sequenced and it was found that they
      were A+T rich and contained different regulatory elements. By using a two step
      procedure (Heparin-sepharose chromatography/DNA affinity chromatography) we
      isolated the protein factor that specifically binds to RIS12. It appeared as a
      double band with apparent molecular masses of 63 and 65 kD.

PMID- 8284199
TI  - Purification and characterization of human 3-methyladenine-DNA glycosylase.
AB  - A human cDNA coding sequence for a 3-methyladenine-DNA glycosylase was expressed
      in Escherichia coli. In addition to the full-length 3-methyladenine-DNA
      glycosylase coding sequence, two other sequences (resulting from differential RNA
      splicing and the truncated anpg cDNA) derived from that sequence were also
      expressed. All three proteins were purified to physical homogeneity and their N
      terminal amino acid sequences are identical to those predicted by the nucleic
      acid sequences. The full-length protein has 293 amino acids coding for a protein
      with a molecular mass of 32 kDa. Polyclonal antibodies against one of the
      proteins react with the other two proteins, and a murine 3-methyladenine-DNA
      glycosylase, but not with several other E. coli DNA repair proteins. All three
      proteins excise 3-methyl-adenine, 7-methylguanine, and 3-methylguanine as well as
      ethylated bases from DNA. The activities of the proteins with respect to ionic
      strength (optimum 100 mM KCl), pH (optimum 7.6), and kinetics for 3-methyladenine
      and 7-methylguanine excision (average values: 3-methyladenine: Km 9 nM and kcat
      10 min-1, 7-methylguanine: Km 29 nM and kcat 0.38 min-1) are comparable. In
      contrast to these results, however, the thermal stability of the full-length and
      splicing variant proteins at 50 degrees C is less than that of the truncated
      protein.

PMID- 8284197
TI  - Compilation of sequence-specific DNA-binding proteins implicated in
      transcriptional control in fungi.

PMID- 8284200
TI  - Specific transcriptional activation in vitro by the herpes simplex virus protein
      VP16.
AB  - The herpes simplex virus protein VP16 interacts with cellular factors, including
      the protein Oct-1, to activate viral immediate early (IE) gene transcription. We
      have reproduced this effect by addition of purified, full-length VP16 and the DNA
      binding 'POU' domain of Oct-1 (Oct-1/POU) to a HeLa cell in vitro transcription
      system. Stimulation of transcription was dependent on the IE-specific element,
      TAATGARAT. In agreement with earlier observations from electrophoretic mobility
      shift assays, activation was not observed when Oct-2/POU, the DNA-binding domain
      from the Oct-2 protein, was substituted for Oct-1/POU. Single round transcription
      assays revealed that, together, VP16 and Oct-1/POU facilitate the assembly of pre
      initiation complexes at target gene promoters.

PMID- 8284201
TI  - A new imprinted gene cloned by a methylation-sensitive genome scanning method.
AB  - We cloned a new imprinted gene by searching for parental-origin-specific CpG
      methylations using methylation-sensitive two-dimensional genome scanning method.
      This gene encodes a putative 51 kDa protein with significant similarity to U2
      small nuclear ribonucleoprotein auxiliary factor small subunits, an essential
      mammalian splicing factor, and is located on mouse chromosome 11, of which
      maternal duplication/paternal deficiency results in a small body.

PMID- 8284202
TI  - Editing does not exist for mammalian selenocysteine tRNAs.
AB  - It has been reported that selenocysteine tRNA from bovine liver is completely
      edited to two isoacceptor species, called tRNA([Ser]SecNCA) and
      tRNA([Ser]SecCmCa), which differ from the gene sequence. We used direct tRNA
      sequencing, mobility shift analyses, primer extension, restriction enzyme
      digestion and single strand conformational polymorphism (SSCP) analyses of
      products from reverse transcription coupled with polymerase chain reaction
      (RT/PCR), sequencing of RT/PCR products and HPLC-coupled mass spectrometry to
      reproduce this result and show here that editing of these tRNAs does not occur.

PMID- 8284203
TI  - The long extra arms of human tRNA((Ser)Sec) and tRNA(Ser) function as major
      identify elements for serylation in an orientation-dependent, but not sequence
      specific manner.
AB  - Selenocysteine tRNA [tRNA((Ser)Sec)] is charged with serine by the same seryl
      tRNA synthetase (SerRS) as the canonical serine tRNAs. Using site-directed
      mutagenesis, we have introduced a series of mutations into human tRNA((Ser)Sec)
      and tRNA(Ser) in order to study the identity elements of tRNA((Ser)Sec) for
      serylation and the effect of the orientation of the extra arm. Our results show
      that the long extra arm is one of the major identity elements for both tRNA(Ser)
      and tRNA((Ser)Sec) and gel retardation assays reveal that it appears to be a
      prerequisite for binding to the cognate synthetase. The long extra arm functions
      in an orientation-dependent, but not in a sequence-specific manner. The
      discriminator base G73 is another important identity element of tRNA((Ser)Sec),
      whereas the T- and D-arms play a minor role for the serylation efficiency.

PMID- 8284204
TI  - Methylation profiles of genomic DNA of mouse developmental brain detected by
      restriction landmark genomic scanning (RLGS) method.
AB  - Restriction landmark genomic scanning using methylation-sensitive endonucleases
      (RLGS-M) is a newly developed powerful method for systematic detection of DNA
      methylation. Using this method, we scanned mouse brain genomic DNAs from various
      developmental stages to detect the transcriptionally active regions. This
      approach is based on the assumption that CpG methylation, particularly of CpG
      islands, might be associated with gene transcriptional regulation. Genomic DNAs
      were prepared from telencephalons of 9.5-, 13.5- and 16.5-day embryos, 1- and 10
      day neonates and adults, followed by subjecting them to RLGS-M and comparing
      their patterns with each other or with that of the adult liver. We used NotI as a
      methylation-sensitive restriction enzyme and surveyed the methylation states of
      2,600 NotI sites, almost of which should correspond to gene loci. Although almost
      all RLGS spots (98%) were present constantly at every developmental stages, only
      a few percent of spots reproducibly appeared and disappeared at different
      developmental stages of the brain (44 spots, 1.7%) and some were tissue-specific
      (10 spots, 0.7%). These data suggest that DNA methylation associated with gene
      transcription is a well-programmed event during the central nervous system (CNS)
      development. Thus, RLGS-M can offer a means for detecting systematically the
      genes in which the state of DNA methylation changes during development of the
      higher organism.

PMID- 8284205
TI  - C-terminal domain (CTD) of RNA-polymerase II and N-terminal segment of the human
      TATA binding protein (TBP) can mediate remote and proximal transcriptional
      activation, respectively.
AB  - Activation domains of mammalian transcription factors can be subdivided into at
      least two functional classes. One, exemplified by the glutamine-rich activation
      domains of Oct and Sp1 factors, mediates transcriptional activation only from a
      proximal promoter position, and in response to an enhancer. The other,
      exemplified by the 'acidic' domain of the viral activator VP16, has the ability
      to activate from remote enhancer as well as from proximal promoter positions.
      Here we report that two proteins of the basal transcription apparatus also
      contain activation domains whose stimulatory effect can be detected in fusion
      proteins containing the GAL4 DNA binding domain. The human TATA-binding protein
      (TBP) contains at its N-terminus a domain with typical 'promoter' activity. We
      propose that the TBP N-terminal region acts as an auxiliary activation domain
      which reinforces the activity of other promoter-bound factors. The largest
      subunit of RNA polymerase II contains at its C-terminus a conserved heptad repeat
      structure (CTD). Both natural and synthetic CTD consensus repeats fused to GAL4
      can activate transcription from remote positions like a typical enhancer-active
      domain. Accordingly we propose that the RNA polymerase II large subunit contains
      a 'portable' domain for transcriptional activation which may synergize with the
      activation domains of enhancer-bound transcription factors.

PMID- 8284206
TI  - The binding of an antisense oligonucleotide to a hairpin structure via triplex
      formation inhibits chemical and biological reactions.
AB  - We have investigated the binding of a 26-mer antisense oligodeoxynucleotide to a
      69-mer DNA hairpin with a 13 base pair stem, bearing an Rsa1 restriction site.
      The 5' part of the 26-mer annealed to a stretch of six purines at the bottom of
      the hairpin. The 3' part was designed to fold back to form a triplex with both
      the stem of the hairpin and with the sequence paired to its own 5' region. Using
      non-denaturing polyacrylamide gel electrophoresis, melting curves (Tm) and
      chemical footprinting, we were able to show the formation of a 'double-hairpin'
      complex between the 69-mer and the 26-mer antisense oligopyrimidines. The
      association was both sequence and pH-dependent. The formation of a double hairpin
      complex was shown to prevent the alkylation of the 69-mer DNA target by an
      oligonucleotide-nitrogen mustard conjugate and to selectively inhibit the action
      of Rsa1.

PMID- 8284207
TI  - The crystal structure of N4-methylcytosine.guanosine base-pairs in the synthetic
      hexanucleotide d(CGCGm4CG).
AB  - The structure of d(CGCGm4CG) were m4C = N4-methylcytosine has been determined by
      crystallographic methods. The crystals are multifaced prisms, with orthorhombic
      space group P2(1)2(1)2(1) and unit cell dimensions of a = 17.98, b = 30.77 and c
      = 44.75A. The asymmetric unit consists of one duplex of hexanucleotide and 49
      waters. The R-factor is 0.189 for 1495 reflections with F > or = sigma(F) to a
      resolution limit of 1.8A. The double helix has a Z-DNA type structure which
      appears to be intermediate in structure to the two previously characterised
      structure types for Z-DNA hexamers. The two m4C.G base-pairs adopt structures
      that are very similar to those of the equivalent base-pairs in the structure of
      the native sequence d(CGCGCG) except for the presence of the methyl groups which
      are trans to the N3 atoms of their parent nucleotides and protrude into the
      solvent region. The introduction of the modified base-pairs into the d(CGCGCG)
      duplex appears to have a minimal effect on the overall base-pair morphology of
      the Z-DNA duplex.

PMID- 8284208
TI  - Monovalent cation effects on intermolecular purine-purine-pyrimidine triple-helix
      formation.
AB  - The binding of a 19-mer guanosine-rich oligodeoxyribonucleotide, TG3TG4TG4TG3T
      (ODN 1), to a complementary polypurine DNA target was investigated by DNase I
      footprinting and restriction endonuclease protection assays. Monovalent cations
      inhibited intermolecular purine-purine-pyrimidine triple-helical DNA formation,
      with K+ and Rb+ being most effective, followed by NH4+ and Na+. Li+ and Cs+ had
      little to no effect. Similar results were observed with the G/A-rich
      oligonucleotide AG3AG4AG4AG3AGCT. Kinetic studies indicated that monovalent
      cations interfered with oligonucleotide-duplex DNA association but did not
      significantly promote triplex dissociation. The observed order of monovalent
      cation inhibition of triplex formation is reminiscent of their effect on
      tetraplex formation with G/T-rich oligonucleotides. However, using
      electrophoretic mobility shift assays we found that the oligonucleotide ODN 1 did
      not appear to form a four-stranded species under conditions promoting tetraplex
      formation. Taken together, our data suggest that processes other than the self
      association of oligonucleotides into tetraplexes might be involved in the
      inhibitory effect of monovalent cations on purine-pyrimidine-purine triplex
      formation.

PMID- 8284209
TI  - Ets transcription factor binding site is required for positive and TNF alpha
      induced negative promoter regulation.
AB  - Thrombomodulin (TM) is expressed on vascular endothelial cells and plays an
      important role in the anticoagulant pathway by maintaining the thrombo-resistance
      of the blood vessel wall. We show that in primary human endothelial cells TM gene
      expression is repressed at the transcriptional level by Tumour necrosis factor
      (TNF alpha) through a protein kinase C independent pathway. The TM promoter is
      highly active in endothelial cells and is inhibited by TNF alpha. The -76/-56
      region mediates both specific high basal activity and TNF alpha-repression. It
      binds a nuclear factor specific to endothelial cells, that appears to belong to
      the Ets-family by various criteria. The -76/-56 region contains three direct
      repeats of the ets-core sequence GGAA that are important for specific high basal
      activity, TNF alpha repression and trans-activation by expression of Ets-1 and 2.
      Although human Ets-1 (h-Ets-1) and chicken c-Ets-1 and 2 stimulate the TM
      promoter through the -76/-56 element, their activity is not suppressed by TNF
      alpha. c-Ets-1 competes and overrides TNF alpha repression in a concentration
      dependent manner. We propose that either a different member of the Ets domain
      protein family, or an Ets-associated co-factor, is the target of the TNF alpha
      signalling cascade in endothelial cells.

PMID- 8284210
TI  - Expression and V(D)J recombination activity of mutated RAG-1 proteins.
AB  - The products of the RAG-1 and RAG-2 genes are essential for the recombination of
      the DNA encoding the antigen receptors of the developing immune system. Little is
      known of the specific role these genes play. We have explored the sequences
      encoding mouse RAG-1 by deleting large parts of the gene and by introducing local
      sequence changes. We find that a RAG-1 gene with 40% of the coding region deleted
      still retains its recombination function. In addition, a series of small
      deletions within the strongly conserved remaining 60% of the coding region was
      tested. Nine out of ten of these prove unable to provide RAG-1 activity, but one
      is quite active. Certain peptide sequences were also specifically targeted for
      mutagenesis. The RAG-1 protein generated from this expression system is
      transported to the nucleus and is degraded with a 15 minute half-life. The fate
      of the proteins made by the deletion mutants were also assessed. Transport of RAG
      1 protein to the nucleus was found even with the most extensive deletions
      studied. The functionality of the deleted proteins is discussed with relation to
      an alignment of RAG-1 sequences from five animal species.

PMID- 8284211
TI  - A single trinucleotide, 5'AGC3'/5'GCT3', of the triplet-repeat disease genes
      confers metal ion-induced non-B DNA structure.
AB  - Expansion of (AGC)n repeats has been associated with genetic disorders called
      triplet-repeat diseases such as Huntington's disease (HD), myotonic muscular
      dystrophy (DM) and Kennedy's disease. To gain insight into the abnormal behavior
      of these repeats, we studied their structural properties in supercoiled DNA.
      Chemical probing revealed that, under physiological salt and pH conditions, Zn2+
      or Co2+ ions induce (AGC)n repeats to adopt a novel non-B DNA structure in which
      all cytosine but none of adenine residues in either strand become unpaired. The
      minimum size of (AGC)n repeat that could form this structure independently of
      neighboring sequences is a single unit of double-stranded trinucleotide,
      5'AGC3'/5'GCT3'. Other trinucleotide units of the same nucleotide composition,
      5'CAG3'/5'CTG3' or 5'GCA3'/5'TGC3', do not form non-B DNA structures. This
      unusual DNA structural properly adopted by a single 5'AGC3'/5'GCT3' trinucleotide
      may contribute to expansion of (AGC)n sequences in triplet-repeat diseases.

PMID- 8284212
TI  - The challenge-phage assay reveals differences in the binding equilibria of mutant
      Escherichia coli Trp super-repressors in vivo.
AB  - The phenotypes of four mutant Escherichia coli Trp repressor proteins with
      increased activities have been examined in vivo using the challenge-phage assay,
      an assay based on a positive genetic selection for DNA binding. These proteins,
      which differ by single amino acid changes from the wild type (Glu13-->Lys, Glu18-
      >Lys, Glu49-->Lys and Ala77-->Val), require less L-tryptophan than wild-type
      repressor for activation in vivo, and are super-aporepressors. However, none of
      the four mutant repressors binds DNA in a corepressor-independent manner. Three
      of the four mutant repressors (with Glu-->Lys changes) are more active when
      complexed with tryptophan, and are superholorepressors. Challenge-phage assays
      with excess tryptophan rank the mutant holorepressors in the same order as
      determined by binding studies in vitro. Challenge-phage assays with limiting
      tryptophan reveal additional phenotypic differences among the mutant proteins.
      These results show that the challenge-phage assay is a robust assay for measuring
      the relative affinities of specific protein-DNA interactions in vivo.

PMID- 8284213
TI  - A closely related group of RNA-dependent RNA polymerases from double-stranded RNA
      viruses.
AB  - Probably one of the first proteinaceous enzymes was an RNA-dependent RNA
      polymerase (RDRP). Although there are several conserved motifs present in the
      RDRPs of most positive and double-stranded RNA (dsRNA) viruses, the RDRPs of the
      dsRNA viruses show no detectable sequence similarity outside the conserved
      motifs. There is now, however, a group of dsRNA viruses of lower eucaryotes whose
      RDRPs are detectably similar. The origin of this sequence similarity appears to
      be common descent from one or more noninfectious viruses of a progenitor cell, an
      origin that predates the differentiation of protozoans and fungi. The cause of
      this preservation of sequence appears to be constraints placed on the RDRP by the
      life-style of these viruses--the maintenance of a stable, persistent,
      noninfectious state.

PMID- 8284214
TI  - High-resolution NMR study of a synthetic oligoribonucleotide with a
      tetranucleotide GAGA loop that is a substrate for the cytotoxic protein, ricin.
AB  - Ricin is a cytotoxic protein that inactivates ribosomes by hydrolyzing the N
      glycosidic bond at position A4324 in eukaryotic 28S rRNA. Its substrate domain
      forms a double helical stem and a 17-base loop that includes the sequence GAGA,
      the second adenosine of which corresponds to A4324. Recently, studies of mutant
      RNAs have shown that the four-nucleotide loop, GAGA, can function as a substrate
      for ricin. To investigate the structure that is recognized by ricin, we studied
      the properties of a short synthetic substrate, the dodecaribonucleotide r
      CUCAGAGAUGAG, which forms a RNA hairpin structure with a GABA loop and a stem of
      four base pairs. The results of NMR spectroscopy allowed us to construct the
      solution structure of this oligonucleotide by restrained molecular-dynamic
      calculations. We found that the stem region exists as an A-form duplex. 5G and 8A
      in the loop region form an unusual G:A base pair, and the phosphodiester backbone
      has a turn between 5G and 6A. This turn seems to help ricin to gain access to 6A
      which is the only site of depurination in the entire structure. The overall
      structure of the GAGA loop is similar to those of the GAAA and GCAA loops that
      have been described but that are not recognized by ricin. Therefore, in addition
      to the adenosine at the depurination site, the neighboring guanosine on the 3'
      side (7G) may also play a role in the recognition mechanism together with 5G and
      8A.

PMID- 8284215
TI  - Discrimination between initiation and elongation of protein biosynthesis in
      yeast: identity assured by a nucleotide modification in the initiator tRNA.
AB  - Cytoplasmic initiator tRNAs from plants and fungi possess an unique 2'
      phosphoribosyl residue at position 64 of their sequence. In yeast tRNA(iMet),
      this modified nucleotide located in the T-stem of the tRNA is a 2'-1''-(beta-O
      ribofuranosyl-5''-phosphoryl)-adenosine. The phosphoribosyl residue of this
      modified nucleoside was removed chemically by treatment involving periodate
      oxidation of tRNA(iMet) and regeneration of the 3'-terminal adenosine with ATP
      (CTP):tRNA nucleotidyl transferase. The role of phosphoribosylation at position
      64 for interaction with elongation factor eEF-1 alpha and initiation factor 2
      (eIF-2) was investigated in the homologous yeast system. Whereas the 5'
      phosphoribosyl residue prevents the binding of Met-tRNA(iMet) to eEF-1 alpha, it
      does not influence the interaction with eIF-2. After removal of the ribosyl
      group, the demodified initiator tRNA showed binding to eEF-1 alpha, but no change
      was detected with respect to the interaction with the initiation factor eIF-2.
      This observation is interpreted to mean that a single modification of an
      eucaryotic initiator tRNA in yeast serves as a negative discriminant for eEF-1
      alpha, thus preventing the initiator tRNA(iMet) from entering the elongation
      cycle of protein biosynthesis.

PMID- 8284216
TI  - Upstream sequences of the myogenin gene convey responsiveness to skeletal muscle
      denervation in transgenic mice.
AB  - Myogenin, as well as other MyoD-related skeletal muscle-specific transcription
      factors, regulate a large number of skeletal muscle genes during myogenic
      differentiation. During later development, innervation suppresses myogenin
      expression in the fetal hind limb musculature. Denervation of skeletal muscle
      reverses the effects of the nerve, and results in the reactivation of myogenin
      expression, as well as of other embryonic muscle proteins. Here we report that
      myogenin upstream sequences confer tissue- and developmental-specific expression
      in transgenic mice harboring a myogenin/chloramphenicol acetyltransferase (CAT)
      reporter construct. Using in situ hybridization to analyze serial sections of
      E12.5 embryos, we found colocalization of CAT and endogenous myogenin transcripts
      in the primordial muscle of the head and limbs, in the intercostal muscle masses,
      and in the most caudal somites. Later in development, we observed that the
      expression of the transgene and endogenous myogenin gene continued to be
      restricted to skeletal muscle but decreased shortly after birth; a period that
      coincides with the innervation of secondary myotubes. Furthermore, denervation of
      the mouse hind limbs induced a 10-fold accumulation of CAT and endogenous
      myogenin transcripts by 1 day after sciatic nerve resection; a 25-fold increase
      was observed by 4 days after denervation. Interestingly, we observed that the
      accumulation of CAT enzyme activity lagged considerably with respect to the
      increase in CAT transcripts. Our results indicate that the cis-acting elements
      that temporally and spatially confine transcription of the gene during embryonic
      development, and that mediate the responses to innervation and denervation of
      muscle, lie within the upstream sequences analyzed in these studies.

PMID- 8284217
TI  - Multiple closely-linked NFAT/octamer and HMG I(Y) binding sites are part of the
      interleukin-4 promoter.
AB  - We show here that the immediate upstream region (from position -12 to -270) of
      the murine interleukin 4 (Il-4) gene harbors a strong cell-type specific
      transcriptional enhancer. In T lymphoma cells, the activity of the Il-4
      promoter/enhancer is stimulated by phorbol esters, Ca++ ionophores and agonists
      of protein kinase A and inhibited by low doses of the immunosuppressant
      cyclosporin A. The Il-4 promoter/enhancer is transcriptionally inactive in B
      lymphoma cells and HeLa cells. DNase I footprint protection experiments revealed
      six sites of the Il-4 promoter/enhancer to be bound by nuclear proteins from
      lymphoid and myeloid cells. Among them are four purine boxes which have been
      described to be important sequence motifs of the Il-2 promoter. They contain the
      motif GGAAA and are recognized by the inducible and cyclosporin A-sensitive
      transcription factor NFAT-1. Three of the Il-4 NFAT-1 sites are closely linked to
      weak binding sites of Octamer factors. Several purine boxes and an AT-rich
      protein-binding site of the Il-4 promoter are also recognized by the high
      mobility group protein HMG I(Y). Whereas the binding of NFAT-1 and Octamer
      factors enhance the activity of the Il-4 promoter, the binding of HMG I(Y)
      suppresses its activity and, therefore, appears to be involved in the suppression
      of Il-4 transcription in resting T lymphocytes.

PMID- 8284218
TI  - An unstructured mRNA region and a 5' hairpin represent important elements of the
      E. coli translation initiation signal determined by using the bacteriophage T7
      gene 1 translation start site.
AB  - Gene 1 of bacteriophage T7 early region--the RNA polymerase gene--is very
      actively translated during the infectious cycle of this phage. A 29 base pair
      fragment of its ribosome binding site containing the initiation triplet, the
      Shine-Dalgarno sequence (S-D), 10 nucleotides (nt) upstream and 6 nt downstream
      of these central elements was cloned into a vector to control the expression of
      the mouse dihydrofolate reductase gene (dhfr). Although all essential parts of
      this translation initiation region (TIR) should be present, this fragment showed
      only very low activity. Computer analysis revealed a potentially inhibitory
      hairpin binding the S-D sequence into its stem base paired to vector-derived
      upstream sequences. Mutational alterations demonstrated that this hairpin was not
      responsible for the low activity. However, addition of 21 nt of the T7 gene 1
      upstream sequence to the 29 base pair fragment were capable of increasing the
      translational efficiency by one order of magnitude. Computer analysis of this
      sequence, including nucleotide shuffling, revealed that it contains a highly
      unstructured region lacking mRNA secondary structures but with a hairpin at its
      5' end, here formed solely by T7 sequences. There was not much difference in
      activity whether the mRNA included or lacked vector-derived sequences upstream of
      the hairpin. Such highly unstructured mRNA regions were found in all very
      efficiently expressed T7 genes without any obvious sequence homologies. The delta
      G values of these regions were higher, i.e. potential secondary structural
      elements were fewer, than in TIR of genes from E. coli. This is likely due to the
      fact that T7 as a lytic phage is relying for successful infection on much
      stronger signals which a cell cannot afford because of the indispensable balanced
      equilibria of its interdependent biochemical processes. When the 5' ends of
      efficient T7 gene mRNA are formed by the action of RNase III they generally start
      with an unstructured region. Efficiently expressed T7 genes within a
      polycistronic mRNA, however, always contain a hairpin preceding the structure
      free sequence. We suggest that the formation of this 5' hairpin is releasing
      enough energy to keep the unstructured regions free of secondary RNA structures
      for sufficient time to give ribosomes and factors a good chance for binding to
      the TIR. In addition, sequences further downstream of the start codon give rise
      to an additional increase in efficiency of the TIR by almost two orders of
      magnitude.

PMID- 8284219
TI  - Specificity of DNA recognition in the nucleoprotein complex for site-specific
      recombination by Tn21 resolvase.
AB  - Resolvases from Tn3-like transposons catalyse site-specific recombination at res
      sites. Each res site has 3 binding sites for resolvase, I, II, and III. The res
      sites in Tn3 and Tn21 have similar structures at I and II but they differ at III.
      Mutagenesis of the Tn21 res site showed that sub-site III is essential for
      recombination though the sequences in III that are recognized by Tn21 resolvase
      are positioned differently from the equivalent sequences in the Tn3 site. The
      deletion of III caused a 1,000-fold drop in the rate of recombination. But other
      mutations at III, changing 3 or 4 consecutive base pairs, caused only 1.5- to 4
      fold decreases in rate, even when the mutations were in target sequences for this
      helix-turn-helix protein. The reason why Tn21 resolvase has similar activities at
      a number of different DNA sequences may be due to the multiplicity of protein
      protein and protein-DNA interactions in its recombinogenic complex. This lack of
      precision may be a general feature of nucleoprotein complexes.

PMID- 8284220
TI  - Heterodimeric DNA-binding dyes designed for energy transfer: stability and
      applications of the DNA complexes.
AB  - Spectroscopic studies of the complexes of double-stranded (ds) DNA with the
      polymethylene-amine linked heterodimers thiazole orange-thiazole blue, thiazole
      orange-ethidium, and fluorescein-ethidium, in each case show efficient energy
      transfer from donor to acceptor chromophores (Benson, S.C., Singh, P. and Glazer,
      A.N. (1993) accompanying manuscript). A quantitative assay of the stability of
      such complexes during gel electrophoresis is presented. The off-rate of dye from
      complexes formed at an initial dsDNA bp:dye ratio > or = 10:1 follows strict
      first-order kinetics. The t0.5 values for the dissociation of a series of related
      dyes provide a quantitative criterion for the design of DNA-binding fluorophores.
      Complexes of dsDNA with the monomeric propidium and cyanine dyes, [1-(9-amino-4,7
      diazanonyl)-3,8-diamino-6-phenyl-phenanthridinium bromide trihydrobromide] and
      (N,N'-tetramethyl-1,3-propanediamino)propyl thiazole orange [4-[3-methyl-2,3
      dihydro-(benzo-1,3-thiazole)-2-methylidenyl]-1-(4 ,4,8-trimethyl-4,8-diazanonyl)
      quinolinium diiodide], are much more stable than those with their widely used
      counterparts, ethidium and thiazole orange. Applications of the new dyes in post
      staining of gels and in the multiplex detection of DNA restriction fragments are
      presented.

PMID- 8284221
TI  - Heterodimeric DNA-binding dyes designed for energy transfer: synthesis and
      spectroscopic properties.
AB  - Heterodimeric dyes are described which bind tightly to double-stranded (dsDNA)
      with large fluorescence enhancements. These dyes are designed to exploit energy
      transfer between donor and acceptor chromophores to tune the separation between
      excitation and emission wavelengths. The dyes described here absorb strongly at
      the 488 nm argon ion line, but emit at different wavelengths, and can be applied
      to multiplex detection of various targets. The chromophores in these dyes, a
      thiazole orange-thiazole blue heterodimer (TOTAB), two different thiazole orange
      ethidium heterodimers (TOED1 and TOED2), and a fluorescein-ethidium heterodimer
      (FED), are in each case linked through polymethyleneamine linkers. The emission
      maxima of the DNA-bound dyes lie at 662 (TOTAB), 614 (TOED 2), and 610 nm (FED).
      The dyes showed a > 100 fold enhancement of the acceptor chromophore fluorescence
      on binding to dsDNA and no sequence selectivity. In comparison with direct 488 nm
      excitation of the constituent monomeric dyes, in the heterodimers the
      fluorescence of the acceptor chromophores was greatly enhanced and the emission
      of the donor chromophores quenched by over 90%. The acceptor emission per DNA
      bound dye molecule was constant from 100 DNA bp:dye to 20 bp:dye and decreased
      sharply at higher dye:DNA ratios.

PMID- 8284222
TI  - Chromatin structure of the EGFR gene suggests a role for intron 1 sequences in
      its regulation in breast cancer cells.
AB  - The chromatin structure of the epidermal growth factor receptor gene (EGFR) has
      been analyzed in several human breast cancer cell lines exhibiting a wide range
      of EGFR expression. Using DNase I, structural differences were identified in the
      promoter, first exon, and intron 1 of the EGFR gene that correlate with its
      expression. Specifically, a DNase I hypersensitive site (DH site) around the exon
      1/intron 1 boundary occurred preferentially in estrogen receptor positive breast
      cancer cell lines with low levels of EGFR expression, while a group of DH sites
      in intron 1 were observed in estrogen receptor negative, high EGFR expressors.
      Additionally, a region in the promoter was sensitive to DNase I in all breast
      cancer cells expressing EGFR, but showed differences in both the level of
      nuclease sensitivity and the extent of the area that was susceptible. Fine
      mapping by native genomic blotting revealed the presence of multiple protein
      footprints in both the promoter and first intron of the EGFR gene in MDA-MB-468
      cells, a breast cancer cell line that overexpresses the EGFR gene. The appearance
      of DH sites in intron 1 associated with high levels of EGFR expression suggests
      that these regions of the gene contain potential enhancer elements, while the
      absence of a DH site at the exon 1/intron 1 boundary when the gene is up
      regulated suggests the action of a repressor that may block transcriptional
      elongation.

PMID- 8284223
TI  - Identification of genes up-regulated in dedifferentiating Nicotania glauca pith
      tissue, using an improved method for constructing a subtractive cDNA library.
AB  - Pith explants of Nicotiana glauca grown in vitro in synthetic medium supplemented
      with 2,4 dichlorophenoxyacetic acid (2, 4 D), are induced to dedifferentiate.
      Treatment with actinomycin D within the first 4-8 h of culture (but not later) is
      lethal and the explants die, implying a requirement for de novo transcription.
      The genes expressed during the initial period of culture are presumably critical
      for subsequent cell survival and proliferation, but so far their identity is
      unknown. We have constructed a subtractive cDNA library, enriched in sequences
      more abundant in dedifferentiating tissue than in pith. The subtractive library
      contains approximately seven major species, two of which, NGSUB7 and NGSUB8, are
      highly abundant. In Northern blots, these two hybridized to mRNA species whose
      abundance increased significantly but transiently during the first 4 to 8 h of
      culture. The sequence of NGSUB7 showed no significant homology at a nucleotide or
      derived amino acid level with any previously reported sequence. NGSUB8 however,
      showed significant homology over part of the derived amino acid sequence to
      several yeast and bacterial proteins with DNA binding function. We propose that
      the two recombinants represent transcripts from two novel genes edeA and edeB,
      which are expressed early in dedifferentiation.

PMID- 8284224
TI  - Conformational changes in E. coli RNA polymerase during promoter recognition.
AB  - We analysed complexes formed during recognition of the lacUV5 promoter by E. coli
      RNA polymerase using formaldehyde as a DNA-protein and protein-protein cross
      linking reagent. Most of the cross-linked complexes specific for the open complex
      (RPO) contain the beta' subunit of RNA polymerase cross-linked with promoter DNA
      in the regions: -50 to -49; -5 to -10; + 5 to +8 and +18 to +21. The protein
      protein cross-linking pattern of contacting subunits is the same for the RNA
      polymerase in solution and in RPO: there are strong sigma-beta' and beta-beta'
      interactions. In contrast, only beta-beta' cross-links were detected in the
      closed (RPC) and intermediate (RPI) complexes. In presence of lac repressor
      before or after formation of the RPO cross-linking pattern is similar with that
      of RPI (RPC) complex.

PMID- 8284225
TI  - Direct genetic selection for a specific RNA-protein interaction.
AB  - The decision between lytic and lysogenic development of temperate DNA
      bacteriophages is determined largely by transcriptional regulation through DNA
      binding proteins. To determine whether a heterologous RNA-binding activity could
      control the developmental fate of a DNA bacteriophage, a derivative of P22 was
      constructed in which the chosen developmental pathway is regulated by an RNA
      binding molecule interacting with its RNA target site located in a phage mRNA. In
      the example presented, lysogenic development of the phage relies upon R17 coat
      protein expression in the susceptible host cell and the availability of a
      suitable coat protein binding site encoded by the phage genome. Through the
      analysis of phage mutants that are able to grow lytically in susceptible cells
      that express the coat protein, additional insights were obtained regarding the
      specific interaction of the R17 coat protein with its RNA binding site. This
      study also suggests a novel and extremely sensitive strategy for selecting RNA
      binding activities in vivo.

PMID- 8284226
TI  - Evaluation of some properties of a phosphorodithioate oligodeoxyribonucleotide
      for antisense application.
AB  - An all phosphorodithioate oligodeoxyribonucleotide (PS2; 17-mer) complementary to
      the coding region of the rabbit beta-globin mRNA was compared with the normal
      (PO2) and phosphorothioate (POS) oligonucleotide of the same size and sequence
      with respect to physicochemical properties and antisense activity in cell-free
      systems. The melting temperature (Tm) of the PS2-cDNA duplex was reduced by 17
      degrees C relative to the PO2-cDNA duplex, compared to 11 degrees C for the POS
      cDNA duplex, suggesting a decreased stability of the duplex with an increasing
      sulfur substitution. Like the POS-derivative, the PS2 oligonucleotide is quite
      stable against exonucleases, but these modified oligonucleotides showed different
      stability towards endonucleases and also towards different sub-cellular fractions
      of MCF-7 cells. During in vitro protein binding studies, the PS2 oligonucleotide
      showed similar binding (10-20%) to that of the PO2 oligonucleotide, while the POS
      oligonucleotide bound 60%. In cell-free translation, the PS2 oligonucleotide
      produced slightly higher specific translation inhibition of rabbit beta-globin
      mRNA compared to that of the PO2 oligonucleotide, and this was true only at
      concentration below 2 mM. The POS-derivative, except at 10 mM concentration,
      always showed higher translation arrest of the rabbit beta-globin mRNA compared
      to that of the other two oligonucleotides. The present study suggests that the
      PS2 oligonucleotide offers very little advantage over the POS oligonucleotide for
      use as an antisense analog.

PMID- 8284227
TI  - Expression and differential regulation of Id1, a dominant negative regulator of
      basic helix-loop-helix transcription factors, in glomerular mesangial cells.
AB  - Id is a family of dominant negative helix-loop-helix (HLH) proteins that block
      cell-specific transcription mediated by basic HLH (bHLH) transcription mediated
      by basic HLH (bHLH) transcription factors. We have analyzed Id1 expression in
      mesangial cells as a first step towards understanding the putative role of bHLH
      transcription factors in cell type-specific gene expression in the kidney.
      Glomerular mesangial cells expressed an abundant 1.1 kb mRNA transcript for Id1,
      but in contrast to other cell types Id1 mRNA was expressed in both randomly
      cycling cells and in serum-deprived, quiescent cultures. When quiescent mesangial
      cells were treated with serum to re-enter G1, Id1 mRNA levels were rapidly (2-4
      h) and transiently down-regulated. Down-regulation of Id1 mRNA following addition
      of serum to mesangial cells was cell type-specific and contrasted with induction
      of Id1 by serum in BHK-21 and 3T3 fibroblasts. Down-regulation of Id1 mRNA
      correlated with mitogenesis and occurred when quiescent cells were treated with
      growth factors that activate G protein-coupled receptors and receptor protein
      tyrosine kinases but not with a non-mitogenic cAMP analog. Down-regulation of Id1
      by growth factors required de novo protein synthesis, suggesting that a labile
      protein was involved. Appearance of E-box DNA binding activity in mesangial cell
      extracts followed down-regulation of Id1 message. Steady state Id1 mRNA levels
      and E-box DNA binding activity were not tightly correlated, suggesting complex
      regulation of Id1 activity. mRNA transcripts for E2A gene products were also
      expressed in mesangial cells, but these cells failed to express mRNAs for
      MyoA/MyoD-related genes. Collectively, these data demonstrate that Id1 is
      expressed in renal mesangial cells and suggest that bHLH complexes might be
      important for transcriptional regulation in the kidney. In addition, the
      observation that Id1 mRNA is transiently down-regulated by serum in mesangial
      cells suggests that Id1 gene expression is more complicated than previously
      appreciated and is tightly regulated in a cell-specific manner.

PMID- 8284228
TI  - Selection of a preribosomal RNA processing site by a nucleolar endoribonuclease
      involves formation of a stable complex.
AB  - A nucleolar endoribonuclease from mouse Ehrlich ascites tumor cells, that has
      been implicated in the endonucleolytic cleavage of mouse precursor ribosomal RNA,
      specifically and stably binds an in vitro-derived rRNA transcript containing the
      +650 early processing site. The specificity of binding was demonstrated by
      mobility shift analysis, glycerol gradient velocity sedimentation analysis, and
      UV-crosslinking studies. Binding did not require Mg2+ and therefore was not
      dependent on cleavage; however, binding was dependent on the presence of the
      early +650 processing site since a pre-rRNA transcript with the +650 processing
      site deleted failed to compete in binding. A small nucleolar RNA component was
      not required for the formation of this stable complex or for the specific
      cleavage of a processing competent pre-rRNA transcript. UV crosslinking studies
      using 32P-labeled 5-azidouridine-substituted pre-rRNA with bound nucleolar
      endoribonuclease identified three closely sized polypeptides of approximately 50,
      approximately 48, and approximately 45 kDa, respectively, that specifically
      crosslinked to the processing competent rRNA transcript. These three polypeptides
      species were identified following ribonuclease digestion and electrophoresis on a
      SDS-polyacrylamide gel. An identical pattern of labeled polypeptides was also
      identified from gel mobility shift analysis where the specifically shifted
      material was U.V. crosslinked. The largest of these polypeptides corresponded to
      the estimated size of the nucleolar endoribonuclease, while the lower molecular
      weight species may represent partially proteolyzed enzyme. Overall, these results
      suggest that the unique specificity of the nucleolar endoribonuclease may, in
      part, be attributed to the formation of a stable complex at the +650 processing
      site for mouse preribosomal RNA, and that formation of this unique stable complex
      affords a means to specifically label the limited amount of available partially
      purified enzyme for sequence analysis.

PMID- 8284229
TI  - PCR primed with VNTR core sequences yields species specific patterns and
      hypervariable probes.
AB  - The use of genomic DNA-based techniques in ecological and evolutionary studies
      has been limited by the availability of suitable probes for species of interest
      due to the technical difficulty of isolating and applying such probes. We have
      developed a simple technique that directs polymerase chain reaction (PCR)
      amplification to regions rich in variable number of tandem repeats (VNTRs). By
      using published VNTR core sequences as primers in PCRs, fragments were amplified
      that showed little variation within a species, but did show differences between
      species. When the amplified fragments were used as probes with genomic DNA
      Southern blots they produced hypervariable single-locus or few-locus patterns in
      fish, birds, and humans. We have named this procedure as Directed Amplification
      of Minisatellite-region DNA (DAMD).

PMID- 8284231
TI  - BspKT6I, a new site-specific endonuclease which cleaves the GATC site two
      nucleotide 5'-protruding ends.

PMID- 8284230
TI  - A nuclear protein with enhanced binding to methylated Sp1 sites in the AIDS virus
      promoter.
AB  - We report here the discovery of HMBP, a protein in nuclei of human T-helper
      lymphocytes and other human cell types, which binds with enhanced affinity to a
      promoter element in the HIV-1 long terminal repeat when that element is
      methylated at CpGs, the target site of the human DNA methyltransferase. This
      promoter element contains three (degenerate) binding sites for Sp1, a general
      activator of transcription. Gel shift assays and footprinting experiments
      indicate that HMBP binding overlaps two of these methylated Sp1 sites. Although
      HMBP binds these methylated Sp1 sites, it does not bind consensus Sp1 sites.
      Competition studies, differences in binding site specificities, binding
      conditions, and, in some cases, chromatographic separation further distinguish
      HMBP from Sp1 and from each of four previously identified methylated-DNA binding
      proteins. HMBP binds hemimethylated DNA in a strand dependent manner. These
      binding characteristics suggest that HMBP may recognize newly replicated DNA and
      thereby play a role in differentiation. If HMBP is able to compete with Sp1 for
      binding at methylated, non-consensus Sp1 sites in vivo and repress transcription,
      it may play a role in AIDS latency.

PMID- 8284232
TI  - Binding capacity and cis-acting efficiency of DNA regulatory sequences can be
      distinguished in an in vivo competition assay.

PMID- 8284233
TI  - A rapid and sensitive method to measure DNA endonuclease activity.

PMID- 8284234
TI  - Localization of single copy gene by PRINS technique.

PMID- 8284235
TI  - World Health Day, April 7, 1993. Theme: handle life with care; prevent violence
      and negligence.

PMID- 8284236
TI  - Protecting, promoting and supporting breast feeding: the special role of
      maternity services.

PMID- 8284237
TI  - International Nurses Day, 1993. Quality, costs, and nursing.

PMID- 8284238
TI  - Psychiatric nursing outside hospitals: some observations.

PMID- 8284239
TI  - Organo phosphate poisoning: a clinical presentation.

PMID- 8284240
TI  - [Immunotherapy and gene therapy of neoplasms].

PMID- 8284241
TI  - [Value of fructosamine test in monitoring of diabetes complicated by
      proteinuria].
AB  - The aim of study was evaluation of fructosamine test in monitoring of diabetes
      mellitus complicated by proteinuria. Twenty patients with type 1 diabetes
      mellitus without proteinuria and 20 diabetic (type 1) patients with proteinuria
      were examined. Absent-present proteinuria was alone differential parameter
      between these groups. Correlations between past-glycaemia and other indices of
      diabetes balance as fructosamine, glycated haemoglobin and fructosamine: albumin
      molal ratio were examined. Results of study suggest that fructosamine test is
      useless in monitoring diabetes with proteinuria, but fructosamine: albumin molal
      ratio is a good parameter in monitoring of either: diabetes mellitus without
      proteinuria and with proteinuria.

PMID- 8284242
TI  - [Effect of hemodialysis on left ventricular function in patients with chronic
      renal failure assessment with radionuclide ventriculography].
AB  - To examine the effects of haemodialysis (HD) on left ventricular (LV) function,
      gated radionuclide ventriculography was conducted before and after HD in 16
      patients with chronic renal failure (CRF) and in 12 healthy persons. The LV
      sectorial function was assessed by subdividing the LV region of interest into 6
      sectors. Global ejection fraction (EF) was unchanged by dialysis (61.4 +/- 8.3%
      before vs. 63.5 +/- 10.4% after) (mean +/- S.D.). EF of sectors 4 and 5 was
      improved significantly (69.3 +/- 10.7% and 85.6 +/- 17.1% before vs. 81.7 +/-
      18.4% and 97.4 +/- 22.0% after) (p < 0.05 and p < 0.05). The peak ejection rate
      (PER) was increased following HD (3.07 +/- 1.03 EDc/s before vs. 3.88 +/- 0.88
      EDc/s after) (p < 0.02). The time to end systole (TES) corrected for R-R interval
      was unchanged by HD (46.3 +/- 6.3 before vs. 43.8 +/- 5.3 after). The peak
      filling rate (PFR) was unchanged by HD (3.41 +/- 0.77 EDc/s before vs. 3.05 +/-
      0.45 EDc/s after). The time to peak filling rate (TPFR) corrected for R-R
      interval was increased (21.8 +/- 5.3 before vs 25.9 +/- 5.0 after) (p < 0.02).
      This study indicates that HD produces beneficial effects on LV systolic function
      in CRF patients and does not improve LV filling in early diastole.

PMID- 8284243
TI  - [Long term echocardiographic evaluation of thrombolytic therapy effect on
      regional function of and aneurysm formation in, the left ventricle in myocardial
      infarction].
AB  - The late effects of thrombolytic therapy on regional left ventricular function
      and ventricular aneurysm formation were evaluated in 91 patients with acute
      myocardial infarction by two-dimensional echocardiography performed at 12 weeks
      and after one year follow-up. 53 patients were randomized to streptokinase plus
      heparin and 38 patients to heparin therapy alone. Wall motion score index (WMSI),
      asynergic area (AA) and left ventricular aneurysm were assessed in serial
      echocardiographic examination. During examination at 12 weeks of acute myocardial
      infarction significant differences between both groups of patients showed: WMSI
      1.43 +/- 0.42 vs 1.78 +/- 0.61 (p < 0.005), AA 26.3 +/- 20.4 vs 39.4 +/- 22.8 (p
      < 0.01), left ventricular aneurysm 3(5.7%) vs 10(26.3%) (p < 0.05). After one
      year of examination significant differences persisted: WMSI 1.35 +/- 0.42 vs 1.62
      +/- 0.59 (p < 0.05) AA 23.2 +/- 22.2 vs 35.8 +/- 24.8 (p < 0.02), left
      ventricular aneurysm 3(6.1%) vs 9(25.7%) (p < 0.05). Our data indicate that
      thrombolytic therapy improves late regional left ventricular function in patients
      with acute myocardial infarction by reducing the extent of regional wall motion
      abnormalities. We find evident reduction in aneurysm formation due to acute
      myocardial infarction in survivors after 12 weeks of observation. The mentioned
      beneficial effects are noted at least up to one year after acute myocardial
      infarction.

PMID- 8284244
TI  - [The role of adhesion molecules in pathogenesis of selected internal diseases].

PMID- 8284245
TI  - [Scribner's shunt as a first step in creation of a Brescia type fistula].
AB  - The aim of this paper is to present the advantages of performing a vascular
      access in two steps in uremic patients requiring urgent hemodialysis. In 15
      patients age 28-68 yrs. (mean 50 yrs.) with end stage renal disease the Quinton
      Scribner shunt linking radial artery with cephalic vein was placed on a forearm,
      and dialysis was started on the same day. After 18-35 days (mean 26 day) in 12
      patients depending on efferent vein arterialization the second step operation of
      creating Cimino-Brescia fistula was performed on the same vessels. The fistula
      was immediately good for punction with standard needles. In 3 patients, due to
      low arterial output the vein condition did not allow for the second step
      operation. The results of our observations show an efficiency of the proposed
      method in establishing an acute and chronic vascular access which was as
      effective as routinely constructed shunts. Our patients avoided complications of
      central vein cannulation and the hospitalization period was shortened.

PMID- 8284246
TI  - [Ventricular arrhythmia in patients treated with diuretics].
AB  - A quantitative and qualitative analysis of ventricular arrhythmia was performed
      in 120 patients (64 men and 56 women, mean age 54 +/- 16) who suffered from
      arterial hypertension or congestive heart failure in the course of organic heart
      disease or ischaemic heart disease. 60 of them were treated with diuretics and
      the other 60 were control group. Neither antiarrhythmic drugs nor digitalis were
      used. There were no signs of left ventricular hypertrophy. Most patients treated
      with diuretics received potassium supplementation. Besides clinical examination
      all patients underwent 24 hours monitoring of Holter ECG. 38 patients treated
      with diuretics were evaluated before and after 6 months of therapy. In the
      diuretic group significantly higher percentage of patients with greater density
      of premature ventricular beats (count of premature ventricular beats
      [PVB]/100,000 heart evolutions) was observed. Number of patients with complex
      ventricular arrhythmia (Lown IVa and IVb) was also greater in this group. Serum
      levels of potassium and magnesium fell within the normal range, but the latter
      was significantly lower (p < 0.05) in those treated with diuretics.

PMID- 8284247
TI  - [Tuberculosis in patients chronically treated with hemodialysis].
AB  - Tuberculosis (tbc) is a significant problem in view of diagnosis and therapy in
      patients on hemodialysis (HD). The object of this study was to analyse cases of
      tbc found among patients treated by HD at the 1st Dept. of Internal Medicine,
      Central Railway Hospital in the years 1971-91. Tuberculosis was found in 10 out
      of 182 patients eligible for analysis (5.5%), 7 of whom were men. Mean HD
      treatment time before diagnosis was 17 months (for the majority--less than 1
      year). One patient had pulmonary tbc 6 had pulmonary tbc with extrapulmonary
      involvement and 3 had extrapulmonary TB only. Six patients had pericardial
      involvement. Clinical examination revealed malaise, lack of appetite, weight
      loss, fever, cough. All cultures were negative. Tuberculin test were positive in
      only 2 cases. In 4 cases tbc was diagnosed on necropsy. In remaining cases tbc
      diagnosis was based on clinical grounds, X-ray films and ineffectiveness of broad
      spectrum antibacterial chemotherapy in conjunction with effective
      antimycobacterial chemotherapy. Agents used were: rifampicin, isoniazide,
      ethambutol. Out of 6 treated patients 5 showed improvement. Two patients had a
      tbc relapse. Mean yearly incidence in our material is 33 times higher than the
      mean yearly incidence in the general Polish population in the years 1971-91.
      CONCLUSIONS: Patients on HD have a high incidence of tbc which presents
      diagnostic difficulties; extrapulmonary organ involvement is the rule in dialysed
      patients; tbc in such a setting may lead to death if untreated; effect of
      antimycobacterial therapy confirms diagnosis.

PMID- 8284248
TI  - [Concomitant symptom syndrome of primary HIV infection].
AB  - A primary HIV infection presenting as an acute viral syndrome in 31-years-old
      male drug addict is described. Two weeks after the probable infection the patient
      presented with fever, sweats, anorexia, vomiting, diarrhoea, myalgia, arthralgia,
      headaches, macular eruption, generalized lymphadenopathy, paresthesia and
      thrombocytopenia. These symptoms lasted 7 weeks. The immune abnormalities
      included an increase of CD8+ lymphocyte percentage resulting in decrease od
      CD4/CD8 ratio. HIV antigenemia was found 4 weeks after the presumed exposure
      whereas anti-HIV became detectable 2 weeks later.

PMID- 8284249
TI  - [Possible applications of NMR spectroscopy in cell metabolism studies in
      different physiological and pathological states. I. Physical basis of nuclear
      magnetic resonance].

PMID- 8284250
TI  - NPFF, a FMRF-NH2-like peptide, blocks opiate effects on ileum contractions.
AB  - We studied the ability of NPFF, a FMRFamide-like peptide with certain antiopiate
      properties, to affect the inhibitory effect of morphine on the electrically
      induced contraction of guinea pig ileum. Neuropeptide FF had no effect when
      administered alone but reduced morphine inhibition in a noncompetitive manner.
      Neuropeptide FF also altered the inhibitory effect of opioid peptides as released
      by an intense electrical stimulation at 10 Hz. These results suggest that NPFF
      receptors exist in guinea pig ileum in association with opiate receptors, and
      that endogenous NPFF may play a role in the diarrhea observed in the morphine
      withdrawal syndrome.

PMID- 8284252
TI  - Proteolytic cleavage of ACTH in corticotropes of sexually mature axolotls
      (Ambystoma mexicanum).
AB  - Immunohistochemical analysis of the pituitary of sexually mature axolotls
      revealed both ACTH(1-39)-related and alpha-MSH-related immunoreactivity present
      in corticotropic cells located in the rostral anterior pituitary. Gel filtration
      analysis indicated that the ACTH(1-39)-sized immunoreactivity and the alpha-MSH
      sized immunoreactivity detected in acid extracts of the axolotl anterior
      pituitary were present in a ratio in a range between 1:1 and 1:0.6. Reversed
      phase HPLC analyses indicated that the alpha-MSH-sized immunoreactivity had the
      same retention time as synthetic ACTH(1-13)-NH2. The corticotropic activity of
      the ACTH(1-39)-sized immunoreactivity and the purified ACTH(1-13)-NH2 was tested
      in a heterologous, larval bullfrog adrenal bioassay system. As expected, the
      ACTH(1-39)-sized immunoreactivity stimulated corticosterone release; however, the
      purified ACTH(1-13)-NH2 lacked glucocorticoid activity. The proteolytic cleavage
      of ACTH in corticotropes of sexually mature axolotls was identical to the
      cleavage events observed in neotenic Ambystoma tigrinum that had not reached
      sexual maturity. These studies indicate that the transient expression of ACTH
      cleavage activity is not affected by the reproductive state of the animal. Since
      axolotls do not undergo metamorphosis, it is possible that events associated with
      metamorphosis may induce the decline in ACTH cleavage activity observed in
      amphibian corticotropes.

PMID- 8284251
TI  - Structure-activity studies of peptide YY(22-36): N-alpha-Ac-[Phe27]PYY(22-36), a
      potent antisecretory peptide in rat jejunum.
AB  - Peptide YY (PYY) and its homologous peptide, neuropeptide Y (NPY), are known to
      exhibit potent antisecretory effects in the intestine. To determine the
      structural requirements to elicit antisecretory effects, we have synthesized
      several analogs of the PYY active site, PYY(22-36), and compared their binding
      affinities and antisecretory potencies in rat jejunum. These investigations
      revealed that the hydroxyl groups of Ser23 and Thr32, as well as the imidazole
      group of His26, are important for activity in the intestine. N-alpha-acetylation
      of PYY(22-36) increased both the binding affinity and antisecretory potency.
      Structure-activity studies with N-alpha-Ac-PYY(22-36) showed that substitution of
      His26 with parachlorophenylalanine (pCl-Phe) or Tyr36 with N-Me-Tyr reduced
      receptor affinity, while replacement of Tyr27 with Phe increased the activity
      substantially. Furthermore, acylation of the alpha-NH2 group with hydrophobic
      groups, myristic and naphthaleneacetic acids, substantially reduced the
      antisecretory potencies but not the binding affinities. Further modification of N
      alpha-Ac-[Phe27]PYY(22-36) may lead to the development of more potent agonist
      compounds, which may provide a framework for the design of a new class of
      antidiarrheal drugs.

PMID- 8284253
TI  - Differential effect of dithiothreitol and DuP 753 on angiotensin II receptor
      subtypes in bovine cerebellar cortex.
AB  - Angiotensin II (AII) receptor subtypes were investigated in bovine cerebellar
      cortical membranes (BCCM) using agonists and antagonists. Differences were
      observed whether the tissue for the characterization was used fresh or frozen. In
      fresh BCCM, AII and angiotensin III (AIII) (not selective), p 
      aminophenylalanine6 -AII ([pNH2Phe6]AII) (AT2 selective), and DuP 753 (AT1
      selective) interacted with two sites, at high and low affinity. In the presence
      of 10 mM dithiothreitol (DTT), the low-affinity site for AIII and [pNH2Phe6]AII
      and the high-affinity site for DuP 753 were no longer detectable. The same effect
      was obtained with 1 microM DuP 753, with only the low-affinity component of
      [pNH2Phe6]AII being resistant to this blocker. In frozen BCCM, DuP 753, PD 123319
      (AT2 selective), and sarcosine1, isoleucine8-AII ([Sar1Ile8] AII) yielded
      monophasic curves. These data confirm the presence of multiple receptors (AT1 and
      AT2) for AII on BCCM and suggest the possibility that within the AT2 receptors,
      one subtype, DTT sensitive, may exist. Alternatively, a heterogeneity in the AT1
      class, with respect to the sensitivity to DuP753, may be considered.

PMID- 8284254
TI  - Silkworm diapause induction activity of myotropic pyrokinin (FXPRLamide) insect
      neuropeptides.
AB  - A family of myotropic neuropeptides sharing the common C-terminal pentapeptide
      Phe-Xxx-Pro-Arg-Leu-NH2 (Xxx = Ser, Thr, Val), known as the pyrokinins, has been
      isolated from the cockroach Leucophaea maderae and locust Locusta migratoria of
      the order Orthoptera. A hormone (Bom-DH) that elicits diapause induction in the
      silkworm Bombyx mori (order Lepidoptera) also contains this C-terminal
      pentapeptide (Xxx = Gly). The orthopteran pyrokinin neuropeptides elicit
      significant diapause-inducing activity in the lepidopteran silkworm. Despite
      containing the sterically bulky, inflexible Val residue in the variable Xxx
      position, the locust pyrokinin Lom-PK is threefold more active than native Bom-DH
      as a diapause induction agent. The C-terminally truncated cockroach
      leucopyrokinin (LPK) fragment, Thr-Ser-Phe-Thr-Pro-Arg-NH2 [LPK(2-7)], proved
      virtually inactive in the silkworm assay, demonstrating the importance of an
      intact C-terminal pentapeptide sequence to diapause induction activity. Bom-DH
      also elicits significant myostimulatory activity in a cockroach hindgut assay,
      although at a level several orders of magnitude less than the native myotropic
      peptide LPK. However, the C-terminal pentapeptide of Bom-DH (Xxx = Gly) is
      equipotent with the LPK C-terminal pentapeptide (Xxx = Thr) as a myostimulatory
      agent. The cross-activity observed for the various pyrokinins suggests that the
      receptors that mediate the disparate physiological processes of diapause in the
      silkworm and hindgut contraction in the cockroach share homologous
      features.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284255
TI  - Estradiol increases the behavioral response to arginine vasopressin (AVP) in the
      medial preoptic-anterior hypothalamus.
AB  - Flank marking, a form of hamster scent marking controlled by arginine vasopressin
      (AVP) in the medial preoptic-anterior hypothalamus (MPOA-AH), is altered by
      circulating levels of gonadal hormones. We hypothesized that gonadal hormones
      influence flank marking either by altering the availability of AVP for release in
      the MPOA-AH or by altering the sensitivity or responsiveness of MPOA-AH neurons
      to AVP. We examined the levels of AVP immunoreactivity (AVP-IR) over the estrous
      cycle in the MPOA-AH and other areas. Arginine vasopressin immunoreactivity did
      not vary in the areas examined as a function of the stage of the estrous cycle.
      In Experiment 2 we measured flank marking after MPOA-AH microinjection of AVP in
      ovariectomized hamsters receiving estradiol or empty Silastic capsules. Hamsters
      implanted with estradiol capsules marked significantly more in response to AVP
      than did hamsters receiving no hormone replacement. These results support the
      hypothesis that estradiol influences flank marking by altering the sensitivity or
      responsiveness of the MPOA-AH or its efferents to AVP. Additionally, we observed
      an unexpected effect of AVP in estradiol-treated hamsters. After microinjection
      with 90 microM AVP, lordosis occurred spontaneously in 60% of the hamsters even
      though no male was present. We suggest that female hamsters may be a useful model
      to further investigate the role of AVP and AVP-like peptides in female sexual
      behavior.

PMID- 8284256
TI  - Purification and primary structure of alligator neurotensin.
AB  - The gastrointestinal neurohormones of reptiles have been poorly characterized
      structurally. Neurotensin has been purified to apparent homogeneity from an
      extract of the small intestine of the alligator, Alligator mississipiensis. The
      primary structure of the peptide (pGlu-Leu-His-Val-Asn-Lys-Ala-Arg-Arg-Pro-Tyr
      Ile-Leu) is identical to that of chicken neurotensin. The data provide further
      evidence for a close phylogenetic relationship between crocodilians and birds.

PMID- 8284257
TI  - Median eminence-afferent vasoactive intestinal peptide (VIP) neurons in the
      hypothalamus: localization by simultaneous tract tracing and immunocytochemistry.
AB  - Retrograde tract tracing and immunocytochemistry were used to investigate the CNS
      source of the VIP that is present in high concentrations in the hypophysial
      portal blood and has been shown to have a stimulatory effect on pituitary
      prolactin secretion. Fluoro-gold (FG), which enters the CNS through areas devoid
      of the blood-brain barrier, such as median eminence, was injected peripherally.
      Brain sections from FG-treated animals were immunostained for VIP. A small
      population of VIP-containing cell bodies in the parvocellular and periventricular
      parts of the paraventricular nucleus (PVN) was also labeled with FG. Vasoactive
      intestinal peptide-immunoreactive perikarya not labeled with FG were also
      observed in the PVN, as well as FG-labeled cells that did not contain VIP. The
      results suggest that some VIP-producing neurons in the PVN project to the median
      eminence and are, therefore, functionally related to pituitary regulation; the
      function of other VIP neurons in the PVN is unknown.

PMID- 8284258
TI  - Vasoactive intestinal peptide (VIP) causes memory impairment in passive avoidance
      responding of the rat.
AB  - Our previous studies demonstrated that CCK-8 and its analog, cerulein (CER), have
      a potent preventive action on experimental amnesia, and that VIP has reciprocal
      action against CCK-8 and CER. Since VIP has been reported to cause amnesia, we
      carried out the present experiments to confirm this action and to examine the
      preventive effect of CER on VIP-induced amnesia. In the passive avoidance
      response, central administration, but not peripheral injection, of VIP caused
      amnesia; the effective portion of the molecule was found to be located in the N
      terminus amino acid sequence. Secretin and PACAP, which have similar molecular
      structures to that of VIP, had no amnestic action. Preadministration of CER
      prevented VIP-induced memory deficit. The VIP antagonists did not affect amnesia
      induced by electroconvulsive shock and scopolamine. It was concluded that CER
      prevents VIP-induced memory deficit in the passive avoidance response of the rat.

PMID- 8284259
TI  - Influence of chronic intracerebroventricular infusion of vasoactive intestinal
      peptide (VIP) on memory processes in Morris water pool test in the rat.
AB  - In our previous study, bolus injection of VIP into the lateral cerebral
      ventricle, at nonphysiological high doses, has been shown to produce amnesia.
      Accordingly, in the present study, VIP was infused chronically into the cerebral
      ventricle of the rat at a rate of 10 ng per day for 2 weeks. During the infusion
      period, the animals were subjected to the Morris water pool test. The VIP
      infusion caused an apparent impairment of memory, particularly in the acquisition
      of new information; VIP(1-12) also caused similar impairment, but to a lesser
      extent. The VIP antagonists did not affect the performance of learned tasks.
      However, cerulein treatment prevented the VIP-induced memory impairment.

PMID- 8284260
TI  - Effects of a biologically active LHRH fragment on CA1 hippocampal neurons.
AB  - The actions of a behaviorally active luteinizing hormone-releasing hormone
      fragment, Ac-LHRH(5-10), on CA1 pyramidal cells were studied utilizing
      conventional intracellular recordings from the in vitro rat hippocampal slice
      preparation. The behaviorally active fragment (10(-7) M) and the natural
      decapeptide [LHRH(1-10), 10(-8) M] had similar actions on CA1 neurons: a long
      duration depolarization associated with increased input resistance, a reduction
      in the slow afterhyperpolarization (AHP), and a decrease in accommodation. In
      contrast, a biologically inactive LHRH fragment [LHRH(1-6) at 10(-7) M] had no
      effect on electrical properties of CA1 neurons. These data suggest that Ac-LHRH(5
      10), like LHRH(1-10), may have a modulatory action on hippocampal neurons.

PMID- 8284261
TI  - Individual variability in Tyr-Gly-Gly formation from enkephalin hydrolysis in
      mouse plasma.
AB  - We examined the effects of captopril (an angiotensin-converting enzyme inhibitor)
      and phosphoramidon (a selective enkephalinase inhibitor) on Tyr-Gly-Gly
      production during Met-enkephalin hydrolysis in plasma samples taken from
      individual outbred Swiss-Webster and inbred C57BL/6J and DBA/2J mice.
      Discriminant analysis procedures identified three distinct plasma profiles of Tyr
      Gly-Gly production in all strains of mice: a captopril-sensitive/phosphoramidon
      insensitive profile, a captopril-insensitive/phosphoramidon-sensitive profile,
      and a moderate captopril and phosphoramidon sensitivity profile. The abilities of
      captopril and phosphoramidon to inhibit Tyr-Gly-Gly production in the same mouse
      plasma sample were highly inversely correlated (r = -0.938). Plasma of Swiss
      Webster mice whose cages and bedding had been changed 24 h prior to sample
      collection was significantly more likely to exhibit the captopril
      sensitive/phosphoramidon-insensitive profile than the plasma of mice whose
      cages/bedding had not been changed for at least 5 days. The results suggest that
      environmental novelty may dramatically alter the activity of a plasma dipeptidyl
      carboxypeptidase system, and thereby regulate behavioral and physiological
      responses to novel experiences.

PMID- 8284262
TI  - Effect of cyclic Arg-Gly-Asp-containing peptide on fibronectin binding to
      activated platelets; role of fibronectin on platelet aggregation.
AB  - The interaction of fibronectin with glycoprotein IIb/IIIa (GPIIb/IIIa) was
      studied. Fibronectin bound to thrombin-stimulated platelets in a calcium
      dependent, specific, and saturable manner with 98,000 molecules/platelet (Kd =
      2.76 x 10(-7) M). The binding was inhibited by other adhesive proteins with IC50S
      of 0.076-0.105 microM and the anti-GPIIb/IIIa monoclonal antibody (LJ-CP8). The
      binding was also inhibited by the cyclic GRGDSPA peptide and the linear GRGDSPA
      peptide with IC50S of 0.223 microM and 3.75 microM, respectively. Native
      fibronectin, the cyclic peptide, and the linear peptide blocked thrombin-induced
      aggregation with IC50 of 0.95 microM, 32 microM, and 190 microM, respectively.
      These observations imply that the conformation of RGD-containing sequence may
      play an important role for an increasing affinity of the binding, and fibronectin
      may prevent thrombus formation by interfering with the interaction between
      fibrinogen and activated GPIIb/IIIa.

PMID- 8284263
TI  - Conformational analysis of synthetic peptides encompassing the factor XI and
      prekallikrein overlapping binding domains of high molecular weight kininogen.
AB  - High molecular weight kininogen, a plasma glycoprotein, circulates as a
      noncovalent complex with either prekallikrein or factor XI, two other plasma
      glycoproteins. The binding domain for factor XI within kininogen, Pro556-Met613
      (58 residues), wholly contains the binding domain for prekallikrein, Ser565
      Lys595 (31 residues), but Trp569-Lys595 (27 residues) retains some ability to
      bind prekallikrein. Complex formation between these proteins is mediated by
      recognition between complementary domains. The 58-residue factor XI peptide
      domain has now been prepared following a strategy of condensation of long-chain
      peptide fragments prepared using orthogonal chemistry protocols. The 58-, 31-,
      and 27-residue peptides assume very different structures in aqueous solution as
      revealed by differential scanning calorimetry, intrinsic fluorescence emission,
      and circular dichroism spectroscopies. Thus, the 31-residue peptide shows a broad
      endothermic transition in differential scanning calorimetry (DSC), but the 58-mer
      undergoes a well-defined, two-state transition (Tm 43 degrees C; transition
      enthalpy approximately 30 kcal/mol). The 58- and 27-residue peptides continuously
      lose structure with increasing temperature, but the 31-mer retains significant
      structure even at temperatures approaching 90 degrees C. Lys595 plays a critical
      role in maintaining structure through electrostatic contacts, probably with
      Asp572 in the N-terminal segment of the 31-residue sequence. Isothermal ligand
      titration calorimetry was used to directly assess the ability of the 31-, 27-,
      and 58-residue peptides to bind prekallikrein. The 31-residue peptide binds
      prekallikrein with 25-fold higher affinity (Kd = 1.0 x 10(-6) M) than the 58
      residue peptide and with 5.4-fold higher affinity than the 27-residue peptide.
      Hence, the essential features of the 31-residue peptide domain required for
      binding prekallikrein are absent in the 58-residue peptide, which is optimized
      for binding factor XI. The results suggest that a conformational change may occur
      within kininogen that causes expression of one domain structure in preference to
      the other.

PMID- 8284264
TI  - Adipokinetic peptide hormone content and biosynthesis during locust development.
AB  - The content and biosynthesis of adipokinetic hormones (Lom-AKH-I, -II. and -III)
      were studied in larval stages and adults of Locusta migratoria. The amount of all
      three AKHs increases with age, although the patterns found for AKH-I and -II
      differ from that for AKH-III. Biosynthetic capacity of the corpus cardiacum for
      the three AKHs increases with age, particularly in larvae, whereas in adults this
      increase is only observed for AKH-III. The amounts of AKH-I and -II stored and
      their active biosynthesis greatly surpass the small quantities needed for
      mobilization of fuels during flight. The data for AKH-III suggest that this
      hormone may be important also during larval stages.

PMID- 8284265
TI  - Angiotensin(1-7) in the spontaneously hypertensive rat.
AB  - We profiled the concentrations of angiotensin I (Ang I), angiotensin II (Ang II),
      and angiotensin(1-7) [Ang(1-7)] by the combination of radioimmunoassay and high
      performance liquid chromatography in the blood of 14-week-old male Wistar-Kyoto
      (WKY) and spontaneously hypertensive rats (SHR) drinking either tap water or a
      solution containing ceranapril (30 mg/kg) or lisinopril (20 mg/kg) for 14 days.
      Differences in the chemical and pharmacokinetic properties of the two converting
      enzyme inhibitors ruled out class-related effects. Plasma renin activity,
      angiotensin converting enzyme (ACE) activity, and plasma levels of Ang I and Ang
      II were the same in vehicle-treated WKY and SHR. In contrast, plasma levels of
      both Ang(1-7) and vasopressin in SHR were 3.7-fold and 2.6-fold higher,
      respectively (p < 0.05). Angiotensin converting enzyme inhibition reduced the
      blood pressure of WKY and SHR, and augmented their intake of water and output of
      urine. These changes were associated with increases in renin activity and plasma
      levels of Ang I and Ang(1-7). In both WKY and SHR, lisinopril had a greater
      effect in inhibiting plasma and cerebrospinal fluid ACE, reducing levels of
      plasma angiotensinogen, and increasing the concentrations of authentic Ang II.
      The principal finding of this study is that plasma Ang(1-7) is the sole component
      of the circulating angiotensin system that is elevated in the established phase
      of genetic hypertension. The finding that chronic inhibition of ACE augments
      circulating levels of Ang(1-7) evidenced the existence of functional pathways for
      the alternate processing of Ang I.

PMID- 8284266
TI  - Differential binding of opioid peptides and other drugs to two subtypes of opioid
      delta ncx binding sites in mouse brain: further evidence for delta receptor
      heterogeneity.
AB  - Research into the functional role of the opioid delta receptor has intensified
      with the recent in vivo identification of delta receptor subtypes, termed delta 1
      and delta 2, which mediate antinociception in the mouse. A variety of data also
      support the hypothesis of an opioid receptor complex composed of distinct, yet
      interacting, mu, delta, and perhaps kappa binding sites. This model postulates
      two classes of delta binding sites: a delta binding site not associated with the
      opioid receptor complex, termed the delta ncx site, and a delta site associated
      with the receptor complex, termed the delta cx site. A major purpose of this
      study was to clarify the relationship between the delta ncx binding sites and the
      delta 1 and delta 2 receptors. Mouse brain membranes were depleted of mu sites by
      pretreatment with the site-directed acylating agent, BIT, and the delta ncx
      binding sites were labeled with [3H][D-Ala2,D-Leu5]enkephalin. Binding surface
      analysis readily resolved two binding sites (delta ncx-1 and delta ncx-2) in the
      absence and presence of 100 mM NaCl. Control experiments with guanine nucleotides
      and the ligand-selectivity analysis indicated that the two sites were not two
      states of a single receptor. Pretreatment of membranes with DALCE, but not
      [Cys4]deltorphin, decreased [3H] [D-Ala2,D-Leu5]enkephalin and [3H][D
      Ser2,Thr6]enkephalin binding. Ligand-selectivity analysis of the two binding
      sites suggested that neither delta ncx binding site had the characteristics
      expected of the delta 2 receptor, and that the delta ncx-1 site, but not the
      delta ncx-2 site, was synonymous with the delta 1 receptor. Moreover, our finding
      that the racemic nonpeptide delta agonist, BW373U86, had high affinity at and
      selectivity for the delta ncx-2 site suggests that this site may be a novel delta
      receptor that mediates some of the effects of BW373U86.

PMID- 8284267
TI  - ANF binding sites in the heart of the quail (Coturnix coturnix japonica).
AB  - The distribution pattern of rat [125I]-atrial natriuretic factor (ANF) binding
      sites in the cardiac regions of the Japanese quail was examined by in vitro
      quantitative autoradiography. Elevated ANF binding densities (519 +/- 121 fmol/mg
      protein) were found in the posterior vena cava, while lower binding levels
      (between 40 and 50 fmol/mg protein) were found in sinus venosus, aortic bulb, and
      endomural vessels, with the ventricular wall having the lowest value (17.6 +/-
      8.8 fmol/mg protein). Scatchard analyses of the ANF binding characteristics (Kd,
      Bmax) revealed both low (94 +/- 55 fmol/mg protein) and high (1161 +/- 69 fmol/mg
      protein) Bmax values. Receptors with higher Kd values than those observed in
      other cardiac regions (Kd between 30 and 60 pM) were found in the vena cava and
      in the heart ventricle (Kd between 113.2 and 229 pM).

PMID- 8284268
TI  - Biphasic effect on nociception and antiopiate activity of the neuropeptide FF
      (FLFQPQRFamide) in the rat.
AB  - The purpose of the present study was to systematically investigate the effects of
      the mammalian neuropeptide Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF) on
      nociception, using the tail-flick test. We report that ICV administration of NPFF
      induces a rapid and short-lasting hyperesthesic effect during day or night, for
      doses ranging from 10 ng to 10 micrograms. During the night, this hyperesthesic
      effect is followed by a long-lasting analgesic effect, the magnitude of which is
      related to the magnitude of the hyperesthesic effect. In addition to this
      intrinsic effect of NPFF, we report that NPFF reverses morphine-induced analgesia
      and that the magnitude of the response elicited by NPFF increases as a function
      of morphine-induced analgesia.

PMID- 8284269
TI  - Local implants of testosterone metabolites regulate vasopressin mRNA in sexually
      dimorphic nuclei of the rat brain.
AB  - Biosynthesis of the neuropeptide vasopressin (VP) in extrahypothalamic neurons is
      dependent on circulating levels of testosterone (T). However, the mechanism by
      which endogenous or peripherally administered T induces VP gene expression in the
      brain has not been established. This study investigated the effects of androgens
      and estrogen in the steroid-dependent expression of VP mRNA in the bed nucleus of
      the stria terminalis (BNST). Testosterone, estrogen, and the T metabolite,
      dihydrotestosterone (DHT), were either peripherally administered or locally
      implanted in cannula into the BNST of castrated male rats to determine whether
      these steroids influence VP gene expression through a local effect within the
      nucleus itself. The results indicate that T does act locally within the BNST,
      since complete restoration of VP mRNA levels occurred in BNST neurons in the
      vicinity of T-containing cannulas but not on the contralateral side. In addition,
      both DHT and estrogen were partially effective in stimulating VP gene expression
      in the BNST, and in combination, synergized to produce the full complement of VP
      gene expression induced by T itself.

PMID- 8284270
TI  - Neuropeptide Y receptor numbers are reduced in the hypothalamus of streptozotocin
      diabetic and food-deprived rats: further evidence of increased activity of
      hypothalamic NPY-containing pathways.
AB  - Neuropeptide Y (NPY) injected into the hypothalamus stimulates feeding and
      affects pituitary secretion. Insulin-deficient diabetes and food deprivation
      markedly increase hypothalamic NPY and NPY mRNA levels, suggesting increased
      activity of NPYergic pathways in the hypothalamus, which could account for
      hyperphagia and neuroendocrine changes in these conditions. To clarify these
      changes, NPY receptor characteristics were compared amongst rats with 3-weeks'
      untreated streptozotocin diabetes, insulin-treated normoglycemic diabetics, and
      non-diabetics, and also in food-deprived (72 h), food-deprived then refed, and in
      freely fed rats. Hypothalamic tissue homogenates (pooled from 3 rats; n = 9 per
      group) in Tris/HCl buffer were incubated with 30 pM [125I]porcine NPY and
      unlabeled NPY (range, 1 pM to 1 microM) for 1 h. Bound and free fractions were
      separated by vacuum filtration. Scatchard analysis revealed both high-affinity
      (Kd 0.3-0.8 nM) and low-affinity (Kd 14-40 nM) NPY receptor populations. Compared
      with nondiabetics, diabetic rats showed significantly reduced numbers (Bmax) of
      both high-affinity receptors (10 +/- 2 vs. 57 +/- 2 pmol/mg protein; p < 0.001)
      and low-affinity receptors (113 +/- 25 vs. 544 +/- 48 pmol/mg protein; p <
      0.001). Insulin treatment partially restored Bmax of both high- and low-affinity
      receptors (24 +/- 1 and 334 +/- 60 pmol/mg protein, respectively; p < 0.01 vs.
      both other groups). Food deprivation also reduced Bmax of high-affinity (36 +/- 2
      vs. 56 +/- 7 pmol/mg protein in freely fed; p < 0.05) and low-affinity receptors
      (288 +/- 6 vs. 457 +/- 17 pmol/mg protein; p < 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8284271
TI  - AT4 receptor binding characteristics: D-amino acid- and glycine-substituted
      peptides.
AB  - The ability of angiotensin IV (AIV) analogs to compete for [125I]AIV binding in
      heat-treated bovine adrenal membranes was examined. Angiotensin IV displayed a Ki
      of 2.63 +/- 0.12 nM. Peptides containing mono-substitutions with glycine or the
      corresponding D-amino acid in positions one, two, or three possessed K(i)s
      greater than 100 nM. Conversely, substitutions at positions four, five, and six
      produced peptides with Kis less than 8 nM. These data suggest that the N-terminal
      domains of the AIV peptide are critical for receptor binding, while the C
      terminal domains play a less decisive role in receptor specificity.

PMID- 8284272
TI  - Glycyl-L-glutamine antagonizes alpha-MSH-elicited thermogenesis.
AB  - The objective of this study was to determine whether glycyl-L-glutamine [beta
      endorphin(30-31)] modulates the thermoregulatory actions of alpha-MSH.
      Microinjection of alpha-MSH (0.06 nmol) into PGE2-responsive thermogenic sites in
      the medial preoptic area of rats generated a hyperthermic response, inducing a
      0.85 +/- 0.19 degrees C rise in colonic temperature (Tc) within 45 min.
      Coadministration of glycyl-L-glutamine (3.0 nmol) completely blocked the
      response, maintaining Tc at baseline levels. This was not attributable to glycyl
      L-glutamine hydrolysis because coadministration of glycine and glutamine had no
      effect on alpha-MSH-induced thermogenesis. Glycyl-L-glutamine, injected alone,
      was similarly without effect. These data indicate that glycyl-L-glutamine
      inhibits alpha-MSH-induced thermogenesis but is devoid of thermoregulatory
      activity itself.

PMID- 8284273
TI  - Expression of CGRP mRNAs in the pink salmon, Oncorhynchus gorbuscha.
AB  - We report the isolation of calcitonin gene-related peptide (CGRP) mRNAs and
      expression of these RNAs in different tissues in the pink salmon, Oncorhynchus
      gorbuscha. Hybridization of poly(A+) RNAs indicated a mature CGRP RNA of 1.1 kb.
      The CGRP-like immunoreactivity occurring in tissues and plasma had the same
      relative molecular weight as the synthetic molecule. Variations in CGRP plasma
      levels were observed during migration, spawning, and postspawning states. These
      data suggest that CGRP may play an important role during the reproductive cycle
      of salmon.

PMID- 8284274
TI  - PC12 cells can be induced to produce, but do not process, the
      neurotensin/neuromedin N precursor.
AB  - Neurotensin and neuromedin N are two biologically active, related peptides that
      are encoded in the same precursor molecule. In the rat, the precursor consists of
      a 169-residue polypeptide containing in its C-terminal region one copy each of
      neurotensin and neuromedin N. Four Lys-Arg sequences, which are thought to
      represent putative processing sites, occur in the precursor molecule. Studies by
      others have shown that rat pheochromocytoma PC12 cells produced neurotensin and
      dramatically increased their neurotensin/neuromedin N precursor mRNA content in
      response to a combination of nerve growth factor, dexamethasone, forskolin, and
      Li+. Here, we investigated the effects of this combination of inducers on the
      posttranslational processing of the neurotensin/neuromedin N precursor in PC12
      cells. Radioimmunoassays coupled to HPLC and arginine-directed tryptic cleavage
      of cell extracts were performed with five antisera specific for precursor
      sequences adjacent to basic doublets. Thus, mature neurotensin and neuromedin N
      represented less than 1% of the total precursor content in PC12 cells. The PC12
      cell line may represent an interesting model with which one could transfect the
      recently cloned prohormone convertases PC1 and PC2, thereby allowing the study of
      the role of these enzymes in the processing of the neurotensin/neuromedin N
      precursor.

PMID- 8284275
TI  - Induction of the neurotensin (NT) gene in PC12 cells gives rise to NT precursor
      (approximately 88%), NT(3-13)-like peptide (approximately 10%), and NT
      (approximately 2%).
AB  - Neurotensin (NT) is coexpressed with catecholamines in sympathetic neurons and
      adrenal chromaffin cells. A pheochromocytoma PC12 cell line can also be induced
      to express the NT gene and produce immunoreactive NT. In the present study, NT
      mRNA was quantified under various hormonal conditions and NT precursor synthesis
      rates were determined by pulse labeling and immunoprecipitation. In addition, NT
      precursor and NT-related products were measured using RIA and were characterized
      using HPLC and Sephadex chromatography. Neurotensin mRNA, NT precursor synthesis,
      and NT precursor/product levels were correlated. Surprisingly, NT appeared to be
      a minor product, both in cells and media: NT precursor (approximately 88%), NT(3
      13)-like peptide (approximately 10%), and NT (approximately 2%). Neurotensin
      added to cultures was not converted to NT(3-13). Treatment of cells with 60 mM
      KCl or various secretagogues induced Ca(2+)-dependent release of NT precursor,
      NT(3-13), and NT in proportion to their cellular contents. These results suggest
      a) that NT precursor processing in induced PC12 cells was much slower than NT
      precursor synthesis, b) that NT(3-13) was a major product and NT a minor one, and
      c) that NT precursor and its products were stored within secretory vesicles.

PMID- 8284276
TI  - Poisoning in children and adolescents.

PMID- 8284277
TI  - Consultation with the specialist. Eye prophylaxis in the newborn infant.

PMID- 8284278
TI  - Sports medicine.

PMID- 8284279
TI  - Index of suspicion. Case 1. Diagnosis: congenital torticollis.

PMID- 8284280
TI  - Index of suspicion. Case 2. Diagnosis: niacin overdose.

PMID- 8284281
TI  - Index of suspicion. Case 3. Diagnosis: neurofibromatosis type 1 with
      hypertension.

PMID- 8284282
TI  - Chronic liver disease in children.

PMID- 8284283
TI  - Consultation with the specialist. Snoring.

PMID- 8284284
TI  - New concepts in the management of encopresis.
AB  - Persistent fecal incontinence without anatomic abnormality, otherwise known as
      soiling or encopresis, frequently brings ridicule and shame to the affected
      child. The disability that it imposes is accentuated by the parental anger,
      guilt, and helplessness it engenders; by the peer hostility and rejection it
      promotes; and by the disgust with which it may be greeted by teachers. Home-based
      pediatric therapy is safe, generally very effective, and rewarding to patient,
      family, and physician. However, it requires a comprehensive understanding of both
      the underlying pathophysiology and the integrated therapeutic program of
      counseling, pharmacotherapy, and behavior modification.

PMID- 8284285
TI  - Fluorescent in situ hybridization (FISH): a new application in the delineation of
      true vs. pseudomosaicism in prenatal diagnosis.
AB  - Metaphase chromosomes and interphase nuclei from nine amniotic fluid cultures
      were studied with fluorescence in situ hybridization (FISH). The samples were
      initially analyzed with routine G-banding and were diagnosed as having true
      mosaicism (five patients) or pseudomosaicism (four patients). In our study, FISH
      analysis could provide additional information to distinguish pseudo- from true
      mosaicism by allowing interphase studies and analysis of an increased number of
      metaphase spreads. These results suggest a multilinear origin of 'in situ'
      colonies of cells.

PMID- 8284286
TI  - Molecular cytogenetic analysis of term placentae suspected of mosaicism using
      fluorescence in situ hybridization.
AB  - In first-trimester chorionic villus sampling (CVS) for prenatal diagnosis,
      abnormal chromosomal findings, such as mosaicism, trisomies, or suspect abnormal
      karyotypes, are found more frequently than at amniocentesis. The fact that these
      chromosomal abnormalities do not always reflect the fetal karyotype but may be
      restricted to the placenta is a major problem in diagnosis and counselling. In
      this paper we present the results of fluorescence in situ hybridization (FISH)
      studies on interphase nuclei of three term placentae investigated because of
      false-positive findings at first-trimester CVS. The chorionic villi of the first
      case showed a mosaic chromosome pattern involving a trisomy 10 cell line and a
      normal cell line, those of the second case a total trisomy 8 cell line, while in
      the third case a complete monosomy X was found. Follow-up amniocentesis in each
      of these three cases revealed a normal karyotype. By using FISH, we were able to
      confirm the presence of the aberrant cell lines, which were all confined to one
      part of the placenta. FISH on interphase nuclei allows the investigation of large
      numbers of cells for the existence of numerical chromosome aberrations in a quick
      and reliable way.

PMID- 8284287
TI  - First-trimester biochemical screening for fetal chromosome abnormalities and
      neural tube defects.
AB  - Alpha-fetoprotein (AFP), unconjugated oestriol (UE3), intact human chorionic
      gonadotrophin (intHCG), and the free beta subunit of chorionic gonadotrophin (F
      beta HCG) were investigated in a series of 21 chromosomally abnormal and 14 open
      neural tube defect pregnancies ascertained from a series of 14,000 prospectively
      collected maternal serum samples at 6-14 weeks' gestation. In 16 cases of Down's
      syndrome, significant reductions were found for AFP (0.65 multiples of the normal
      median) and UE3 (0.67 MOM). IntHCG levels were unaltered (0.97 MOM) but a
      significant increase was found for F beta HCG (1.96 MOM). Significant
      correlations were found for AFP and UE3 in the controls and for intHCG and F beta
      HCG in both the control and the Down's syndrome pregnancies. In a group of five
      trisomy 18 pregnancies, median MOMs were for AFP 0.71, for UE3 0.34, for intHCG
      0.27, and for F beta HCG 0.15. None of 13 pregnancies with open neural tube
      defects at 8-13 weeks gestation had elevated maternal serum AFP levels, whereas
      matched second-trimester samples from the same pregnancies at 16-18 weeks
      gestation all had significantly elevated AFP levels. Thus, biochemical screening
      for chromosome abnormalities may be practicable in the first trimester using free
      beta human chorionic gonadotrophin in combination with AFP and maternal age.
      However, a separate screening protocol using AFP at 15-18 weeks gestation would
      still be required for effective detection of neural tube defects.

PMID- 8284288
TI  - Is selective abortion for a genetic disease an issue for the medical profession?
      A comparative study of Quebec and France.
AB  - This article discusses the results of a study of the stand and attitudes of
      physicians from the Picardie, Nord-Pas-de-Calais region in France and the
      province of Quebec (Canada) regarding abortion following the diagnosis of a fetal
      anomaly by ultrasound, amniocentesis, or chorionic villus sampling. The study
      examined the degree of acceptability of abortion for several specific conditions
      as well as the physicians' perceptions of their role in the women's decision to
      abort. The study shows a consensus (over 75 per cent of the physicians surveyed)
      for aborting a fetus with trisomy 21. There is a similar consensus, except among
      Francophones in Quebec, for muscular dystrophy, cystic fibrosis, and Huntington
      disease. Conversely, there is no consensus (below 60 per cent) for several
      anomalies. In these cases, Quebec Anglophone physicians find abortion more
      acceptable than Quebec Francophone or French physicians. Concerning the role of
      the practitioners in the decision to abort, physicians in France tend to be much
      more directive than their overseas colleagues. Several hypotheses are suggested
      to explain the difference between the three groups surveyed.

PMID- 8284289
TI  - Attitudes toward abortion for fetal anomaly in the second vs. the third
      trimester: a survey of Parisian obstetricians.
AB  - Cross-cultural differences exist in prenatal diagnosis and abortion for fetal
      anomaly, stemming from variations in laws, reimbursement policies, litigation,
      physicians' decision-making authority, and attitudes toward the prevention of
      handicaps. The first part of this paper discusses such differences in France and
      the U.S. The second part describes a survey of practising obstetricians in Paris,
      designed to assess (1) their attitudes toward pregnancy termination for various
      conditions, (2) their concern about fetal viability, (3) their desire for
      diagnostic certainty before justifying a late abortion, and (4) their perceived
      role in such decision-making. Among the 64.8 per cent (N = 217) who responded,
      the majority supported third-trimester termination (TTT) for diseases such as
      spina bifida, trisomy 21, microcephaly, and Duchenne muscular dystrophy; 30-59
      per cent supported TTT for cystic fibrosis and sickle cell disease; and 22-29 per
      cent supported TTT for haemophilia, tetralogy of Fallot, limb amputation, and
      Turner and Klinefelter syndromes. Obstetricians who approved of abortion across
      trimesters were less concerned with the certainty of diagnosis than its severity,
      more likely to think that abortion ought to be the parents' choice, but more
      likely to report making a recommendation to the parents about whether to abort a
      fetus. Such permissive abortion attitudes might imply more permissive prenatal
      diagnosis and abortion practice among Parisian obstetricians, which might lead to
      increased migration of patients from other E.C. countries. Cross-cultural
      variation in obstetric practice suggests that an international registry of
      pregnancies terminated for medical reasons, enabling further study of this issue,
      would be valuable.

PMID- 8284290
TI  - Cytogenetic analysis of 2928 CVS samples and 1075 amniocenteses from randomized
      studies.
AB  - We report cytogenetic results from a randomized Danish chorionic villus sampling
      (CVS) and amniocentesis (AC) study including 2928 placental and 1075 amniotic
      fluid specimens processed in the same laboratory. The results are presented in
      groups comparing CVS with amniocentesis and transabdominal (TA) CVS with
      transcervical (TC) CVS as randomized. More abnormalities and more ambiguous
      diagnostic problems were found in placental tissues than in amniotic cells. There
      were no diagnostic errors and no incorrect sex predictions. Mosaicism was
      detected in 1 per cent of all cases of CVS (discordancies included). When
      confirmation studies were done, 90 per cent were found to be confined to the
      placenta. Eight cases (0.7 per cent) of mosaicism/pseudomosaicism were seen in
      amniotic fluid specimens, and two cases of five with confirmation studies were
      confirmed in the fetus. The rate of mosaicism/pseudomosaicism in CVS and AC
      specimens differed (p < 0.05). The rate of pseudomosaicism in cultures of villi
      and amniotic fluid cells was 0.5 and 0.6 per cent, respectively. Single-cell
      aneuploidy was observed in 1.8 per cent of villi and 1.4 per cent of amniotic
      fluid cell specimens. Maternal cell contamination (MCC) was seen more often after
      TC sampling (4.5 per cent) compared with TA sampling (1.5 per cent), but posed no
      problems in interpretation. Compared with the processing of cultured specimens,
      the short-term method of preparation of villi in our laboratory doubled the
      technicians' workload. For practical and economic reasons we have ceased the
      routine use of short-term preparations.

PMID- 8284291
TI  - Women's opinions on the offer and use of maternal serum screening.
AB  - We studied the opinions and experiences concerning maternal serum screening of
      two groups of women: (A) women who were not eligible for prenatal diagnosis; and
      (B) women for whom prenatal diagnosis was available because of advanced maternal
      age, and who either underwent chorionic villus sampling or amniocentesis. Many of
      the women were in favour of the availability of serum screening and would apply
      for this test in a future pregnancy. This applied also to many respondents who
      had previously undergone prenatal diagnosis. Most of these women, however, did
      not intend to decline diagnostic amniocentesis if the screening results did not
      indicate an increased risk. The majority of the group of respondents of 36 years
      and over did not consider it acceptable if age indication was dropped altogether.
      A system based on serum screening will have other implications than a policy
      based on age indication, since specific individual risk assessment is perceived
      as being of more significance than a risk statistically derived from age alone.
      Serum screening is often seen as a means of reassurance and many women are not
      aware of the possible drawbacks. As technology becomes increasingly complicated,
      counselling has to be adjusted correspondingly. Further research is needed to
      establish whether and how distress can be minimized and well-considered
      individual choice can be achieved.

PMID- 8284292
TI  - Measurement of the fetal mandible--feasibility and construction of a centile
      chart.
AB  - The prenatal diagnosis of micrognathia is usually based on a subjective
      impression of the size of the jaw when examining the fetal profile. We have
      constructed a centile chart for mandibular length between 12 and 27 post
      menstrual weeks in a cross-sectional study of 184 fetuses. The application of
      this chart in clinical practice may permit a more objective diagnosis of
      micrognathia in the prenatal period.

PMID- 8284293
TI  - Verification of carrier status for Becker muscular dystrophy from analysis of a
      blighted ovum.
AB  - The polymerase chain reaction (PCR) was used on material from a blighted ovum to
      confirm indirectly the carrier status of a woman with a family history of Becker
      muscular dystrophy. Conventional testing including creatine kinase levels, muscle
      biopsy, and EMG had been inconclusive, and on the basis of one elevated creatine
      kinase level, the woman had been designated a possible carrier. Ultrasound
      examination at 10 weeks of pregnancy indicated a blighted ovum, from which DNA
      was subsequently extracted and subjected to PCR testing for determination of sex
      and genotypic status with respect to the known familial deletion of the
      dystrophin gene. The blighted ovum was found to have a Y chromosome and also to
      be deleted for at least exon 6 of the dystrophin gene, indirectly indicating that
      the mother most likely carried the family mutation for Becker muscular dystrophy.

PMID- 8284294
TI  - On the parental origin of the X's in a prenatally diagnosed 49,XXXXX syndrome.
AB  - A 49,XXXXX fetus was detected in amniotic fluid cell cultures from a 39-year-old
      mother. On ultrasonography, growth retardation and bilateral radioulnar
      synostosis were found. Additional clinical manifestations were mild facial
      anomalies and hypoplastic ovaries depleted of oocytes. Molecular analysis showed
      that this aneuploidy arose by successive maternal non-disjunction.

PMID- 8284295
TI  - How accurate does rapid fetal karyotyping need to be? Case of unbalanced t(13;18)

PMID- 8284296
TI  - First-trimester prenatal diagnosis of non-ketotic hyperglycinaemia by a micro
      assay of glycine cleavage enzyme.

PMID- 8284297
TI  - Prenatal diagnosis of spina bifida aperta after first-trimester valproate
      exposure.

PMID- 8284298
TI  - Second-trimester CA 125 and Down's syndrome.

PMID- 8284299
TI  - A biopsychological approach to temporomandibular joint pain and other chronic
      facial pain. Part II: Broadening of spectrum of treatments.
AB  - The multidimensional nature of chronic pain often requires a variety of
      therapies, ranging from reassurance and relaxation training to invasive
      treatment. The high spontaneous rate of recovery in temporomandibular dysfunction
      can lead to overtreatment of a benign disorder. However, a tendency to undertreat
      chronic facial pain and malignant pain conditions also exists. In therapy
      resistant chronic pain cases, alternative therapies merit consideration, even
      though they may generally be rejected by Western medicine as unscientific and no
      better than placebo. Working with chronic pain patients is demanding and
      fulfilling but can be wearing. Doctors, nurses and other staff involved in pain
      treatment should take part in supervision of therapeutic work, to prevent burn
      out. This article offers guidelines for treatments rarely considered as routine
      therapy, and describes an extreme case of therapy-resistant chronic facial pain.

PMID- 8284300
TI  - Dental tissues involved in exarticulation, root resorption and factors
      influencing prognosis in relation to replanted teeth. A review.
AB  - Prognosis in relation to an exarticulated, replanted tooth is poor. Late
      complications are frequent and often lead to tooth loss. However, the root of a
      replanted, avulsed tooth may be slowly resorbed preserving alveolar width and
      postpones replacement of the tooth to a more convenient time. During healing
      following transplantation or replantation of teeth, various dental and oral
      structures are involved. Late complications relate to various factors. Tissues
      and factors involved are reviewed. Knowledge of this subject derives mostly from
      results of transplantation studies in animals.

PMID- 8284301
TI  - A two-year follow-up of temporomandibular joint disk displacement without
      reduction in 22 subjects.
AB  - Twenty-two subjects with clinically diagnosed unilateral anterior disk
      displacement were followed up for two years. Seventeen of the patients were women
      and five were men, with ages ranging from 17 to 68 years (median 27 years). In 20
      cases the duration of locking at the time of the examination was less than 6
      months; the other two cases had experienced locking for more than 6 months but
      less than one year. Case histories were recorded and clinical examinations
      performed according to accepted principles, followed by calculation of Helkimo's
      anamnestic dysfunction index Ai and clinical dysfunction index Di. The patients
      were treated using full coverage splints combined with occlusal adjustment.
      Follow-up examinations were made after 6 months, one year and two years. At the
      time of the first visit, 17 patients had severe subjective symptoms such as
      difficulty in opening the mouth wide and pain on movement of the mandible, while
      five experienced locking without subjective symptoms. All patients apart from one
      belonged to Di III and had a maximal mouth opening capacity ranging from 24 to 38
      mm. During follow-up, one patient was treated surgically because of continuous
      severe symptoms; in one case, spontaneous disk reduction was confirmed by MR
      imaging. At the last examination the rest of the patients (n = 20) had a mouth
      opening capacity ranging from 31 to 60 mm and belonged to Di II. However, eight
      patients were completely symptom free and 12 had only mild symptoms. All patients
      regarded their condition and good as were able to manage well.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8284302
TI  - Dentistry in the future--on the role and goal of basic research in oral biology.
AB  - Examination of the state of affairs of oral biology cannot be endeavoured without
      considering the mutual interactions and interdependencies of sciences, and
      without considering the impact human acts will exert on these developments. Oral
      biology deals with the biochemical, chemical, molecular biologic, general
      biologic and physical aspects of all processes that take place in the oral
      cavity, in the masticatory organ, and in tissues and body fluids that are
      associated with the above processes. Oral biology also reaps the harvest sown by
      (other) basic sciences. From the methodological point of view, oral biology is
      indistinguishable from basic sciences; it is the anatomical object that makes it
      specific. Oral biology cannot be regarded as "big science" (i.e. compared with
      the human genome project, space research, AIDS research etc.). This fact may
      preserve the attractiveness of oral biology. Important science--this concerns
      oral biology as well--still emerges in smaller settings, although there are omens
      that large research cartels will swallow larger and larger portions of research
      appropriations. A key to staying competitive is to use new science sources and-
      in some cases--to join bigger groups. Once upon a time oral biologists--or
      scientists in general--assumed that a record of solid accomplishments was
      sufficient to maintain research support. Today, in several countries, politics
      and public visibility unfortunately determine the funding privileges. Provided
      that human operations on earth will render future development of sciences
      possible, the future of oral biology will depend 1) on concomitant development in
      the above basic fields, and 2) on innovations in the individual psyches. This
      combination will unravel the structure of genes involved in the development and
      metabolism of oral processes, clone important salivary and connective tissue
      proteins, and control most important oral diseases. To achieve these goals, oral
      biology must attract young talent and funding must be made available. There is no
      shortcut, however. Individual efforts and persistent labouring at the laboratory
      bench will still remain prerequisites. Although successful prevention of certain
      oral diseases, such as dental caries, may be possible in certain regions of the
      Earth, the prospects are much gloomier globally.

PMID- 8284303
TI  - Periodontal health related to plasma ascorbic acid.
AB  - The exact relationship between plaque-induced periodontal diseases and vitamin C
      deficiency is not known. The aim of this study was to evaluate the possible
      effect of ascorbic acid (AA) on the severity of periodontal diseases. The
      periodontal condition of 75 dentulous subjects with a low level of AA in the
      plasma (< or = 25 mumol/l) was compared with that of 75 control subjects (plasma
      level > or = 50 mumol/l) matched for age, sex and number of teeth. The subjects
      were asked to list foods containing AA in their diet, and intake of AA in
      milligrams per day was calculated. The daily diet of the study subjects contained
      on average 52 mg +/- 24.9 (SD) of AA, and that of the controls 77 mg +/- 43.2
      (SD). For each individual, site-specific recordings for the presence or absence
      of plaque and supra- and subgingival calculus, filling overhangs, gingival
      bleeding after probing, probing pocket depth, and gingival recession were made
      clinically in a double blind examination carried out by one dentist. Five per
      cent of the subjects in the study group (low plasma level of AA) and 18 per cent
      of the controls had healthy periodontal tissues. The proportion of sites in which
      bleeding after probing and a probing pocket depth of 4 mm or over were observed
      was significantly higher in the study group than in the controls. Sixty per cent
      of the subjects in the study group and 37 per cent of the controls had
      pathological pockets of 4 mm or over.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284304
TI  - The ethos of the military surgeon.

PMID- 8284305
TI  - Human germ-line gene therapy: new territory?

PMID- 8284306
TI  - Medical education and health care reform.

PMID- 8284307
TI  - Baconian science, nineteenth-century alternative practice, and clinical medicine.

PMID- 8284309
TI  - Questions and reflections. People-poisoning.

PMID- 8284308
TI  - Remorse--end stage for the combat physician?

PMID- 8284310
TI  - Defensive medicine.

PMID- 8284311
TI  - Unintended plagiarism.

PMID- 8284312
TI  - The making of a physician.

PMID- 8284313
TI  - The making of a physician.

PMID- 8284314
TI  - In regard to residency contract withdrawal.

PMID- 8284315
TI  - Pandemic, medicine, and public health: Yersinia pestis and fourteenth-century
      European culture.

PMID- 8284316
TI  - Thermodynamics of the binding of hematoporphyrin ester, a hematoporphyrin
      derivative-like photosensitizer, and its components to human serum albumin, human
      high-density lipoprotein and human low-density lipoprotein.
AB  - The phenomena of the high affinity of porphyrins to the human serum proteins,
      albumin, high-density lipoproteins (HDL) and low-density lipoproteins (LDL) is
      well established. Yet, evaluation of the activities of these proteins as
      endogenous porphyrin carriers, especially with respect to receptor-mediated
      porphyrin uptake into tumor cells, the merits of which are still in dispute,
      requires more quantitative protein-porphyrin binding data. As a continuation of
      previous studies on this issue, the binding of several porphyrin systems to each
      of the three proteins, employing previously developed spectral methodologies, was
      studied. The specific systems reported here are hematoporphyrin ester (HPE),
      which is a novel hematoporphyrin derivative (HPD)-like system, two porphyrin
      trimers (denoted O1 and O2) and a porphyrin dimer (denoted O3) isolated from HPE.
      Human serum albumin (HSA) was found to have a single high-affinity site for the
      monomeric components of HPE, with an equilibrium binding constant of 3.6 x 10(6).
      The equilibrium parameters determined for the binding of the three HPE-isolated
      oligomers to each of the serum proteins are: (1) Binding constants (Kb') of 2.3 x
      10(6), 6.9 x 10(4) and 1.5 x 10(4) and number of sites per protein molecule (n)
      of 3, 1 and 5, for the binding of O1, O2 and O3, respectively, to HSA. (2) Kb'
      values of 15.5 x 10(3), 15.3 x 10(3) and 6.6 x 10(3) and n values of 1, 2 and 2,
      for the binding of O1, O2 and O3, respectively, to HDL.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8284317
TI  - Flavin-photosensitized monomerization of dimethylthymine cyclobutane dimer in the
      presence of magnesium perchlorate.
AB  - We have investigated the photosensitized monomerization of the cis,syn
      cyclobutane dimer of 1,3-dimethylthymine using riboflavin tetraacetate and a 5
      deazaflavin derivative as photosensitizer. Although little monomerization of the
      dimer is induced by photoexcitation of the flavins in the absence of any
      additives, the flavins can function as an efficient photosensitizer in the
      presence of magnesium perchlorate. Mechanistic studies involving spectroscopic,
      quantum-yield and flash-photolysis measurements demonstrated that the
      photosensitized monomerization exclusively proceeds through electron transfer
      from the dimer to the triplet flavins complexed with Mg2+. The effects of
      magnesium perchlorate are compared with those on the chloranil-photosensitized
      monomerization and also with the effects of HClO4 on the flavin-photosensitized
      reaction.

PMID- 8284318
TI  - Fluorescence line-narrowing studies of antibody-benzo[a]pyrene tetrol complexes.
AB  - Benzo[a]pyrene tetrol (BPT) was used as a fluorescent probe to investigate the
      nature of antigen binding by two different monoclonal antibodies (MAb) that
      recognize a variety of derivatives of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-
      tetrahydrobenzo[a]pyrenes (BPDE). Fluorescence line-narrowed spectra of the
      physical complexes of BPT formed with antibodies 8E11 and 3C3 were recorded at 4
      K by employing vibronic excitation into the S1 electronic state. The frequencies
      of the vibrational modes of the S1 state were only marginally affected, though
      changes in relative intensities of some bands were observed. Fluorescence spectra
      recorded at 77 K by excitation into the S2 state showed that the (0,0)
      fluorescence emission of BPT was shifted to red on complex formation. Intensity
      ratios of the (0,0) band and the main vibrational band at 1300 cm-1 were used to
      assess the degree of interior binding of the chromophore. Quenching studies with
      acrylamide were employed to designate the complexes as type I, solvent
      inaccessible, or type II, solvent accessible. These studies also indicated that
      antibody 3C3 complexes tend to be more heterogeneous compared to the 8E11
      complex. Deuterated BPT-d-12 also formed complexes with both antibodies, however,
      with different quenching behavior.

PMID- 8284319
TI  - Comparative potency of broad-band and narrow-band phototherapy sources to induce
      edema, sunburn cells and urocanic acid photoisomerization in hairless mouse skin.
AB  - The Philips TL01 narrow-band (311-313 nm) fluorescent lamp provides effective
      phototherapy for psoriasis and atopic eczema while emitting less erythemogenic
      radiation than conventional broad-band (e.g. Philips TL12; 270-350 nm) sources.
      We studied the potency of TL01 and TL12 radiation to induce edema and sunburn
      cells (SBC) and to photoisomerize naturally occurring trans-urocanic acid (UCA)
      to cis-UCA in hairless mouse skin. Cis-UCA has immunosuppressive properties and
      is a putative mediator of UV-induced suppression of immune responses. For each
      source, there was UV dose dependence for all three responses. Within the dose
      ranges used, the potency ratio of TL12:TL01 radiation to induce equivalent edema
      and SBC was about 6:1. However, the potency ratio to induce cis-UCA was less than
      2.3:1. Therefore, at a given level of edema or SBC induction, TL01 was more
      efficient than TL12 at UCA photoisomerization. The TL01 induction of
      immunomodulating cis-UCA, while causing minimal skin injury, may relate to the
      therapeutic efficacy of this source in skin conditions with an immunological
      component.

PMID- 8284321
TI  - Relaxation of vascular smooth muscle induced by low-power laser radiation.
AB  - The relaxation of rabbit aorta rings induced by low-power laser radiation was
      investigated in vitro to determine the location of the chromophore(s) responsible
      for this response and evaluate possible mechanisms. An action spectrum for
      relaxation was measured on rabbit thoracic aorta rings precontracted with
      norepinephrine. The decrease in isometric tension was measured during exposure to
      laser light (351-625 nm) delivered via a fiber optic to a small spot on the
      adventitial surface. The shortest UV wavelength (351 nm) was 35-fold more
      effective than 390 nm and 1700-fold more effective than 460 nm. Ultraviolet
      wavelengths also produced greater maximum relaxation (0.40-0.45) than visible
      wavelengths (0.20-0.25), suggesting that photovasorelaxation involves more than
      one chromophore. The adventitial layer was not necessary for photovasorelaxation,
      indicating that the light is absorbed by a chromophore in the medial layer. The
      same degree of relaxation was obtained on rings without adventitia when either
      one-half of the ring, or a small spot was irradiated indicating that
      communication between smooth muscle cells spreads a signal from the area
      illuminated to the entire ring. The mechanism for photovasorelaxation was
      investigated using potential inhibitors. N-monomethyl-L-arginine and N-amino-L
      arginine, inhibitors of nitric oxide synthase, did not alter photovasorelaxation
      nor did indomethacin, an inhibitor of cyclooxygenase, and zinc protoporphyrin, an
      inhibitor of heme oxygenase.

PMID- 8284320
TI  - In vitro photodynamic effects of lysyl chlorin p6: cell survival, localization
      and ultrastructural changes.
AB  - The in vitro cell survival, localization and ultrastructural changes following
      irradiation were examined in 9L glioma cells sensitized with a new
      photosensitizer, lysyl chlorin p6 (LCP). In clonogenic assays, LCP was 10-100
      fold more phototoxic than photofrin II on a microgram/mL basis. Lysyl chlorin p6
      uptake was blocked when cells were incubated at 2 degrees C. In view of the
      chemical properties of LCP, this finding indicates that uptake probably occurred
      through the endocytic pathway. Fluorescence studies showed LCP localized in a
      region of the endocytic compartment similar in size, shape and distribution to
      that labeled by lucifer yellow CH (LY), as well as localizing diffusely
      throughout the perinuclear cytoplasm. Cells stained with both LY and LCP,
      however, had distinctly separate regions of staining. Lysyl chlorin p6
      localization differed from that of fluorescent probes labeling the mitochondria,
      Golgi apparatus and endoplasmic reticulum. Ultrastructural changes at both 2 and
      30 min after laser irradiation were similar. Mitochondria were often condensed or
      swollen and also had constrictions and cytoplasmic invaginations. The Golgi
      apparatus, perinuclear space and rough endoplasmic reticulum (RER) were dilated.
      These data demonstrate that LCP localizes in a portion of the endosomal
      compartment, but that morphologic damage initially occurs in the mitochondria,
      Golgi apparatus and RER.

PMID- 8284322
TI  - The effect of differentiation on photosensitizer uptake by HL60 cells.
AB  - The capability of human promyelocytic leukemia cells HL60 to be induced to
      differentiate to various stages along the monocytic or myelocytic pathway was
      exploited for investigation of the uptake of selected photosensitizers by diverse
      types of cells of the same origin. The results showed that there was no
      substantial difference in photofrin uptake between noninduced HL60 cells,
      immature monocytes, immature neutrophils and cells differentiated along the
      eosinophilic pathway. In contrast, HL60 cells differentiated into macrophages
      (HL60 phi) exhibited markedly increased photofrin uptake, which was further
      enhanced by their pretreatment with bacterial lipopolysaccharide. Similar results
      were obtained with other photosensitizers tested: di- and tetrasulfonated
      aluminum phthalocyanines (A1PcS2 and A1PcS4), tetrasulfonated zinc phthalocyanine
      (ZnPcS4), tetraphenylporphine tetrasulfonate (TPPS4) and benzoporphyrin
      derivative monoacid (BPD). Despite marked differences in the state of self
      aggregation and other chemical properties of these compounds, the degree of their
      preferential uptake by HL60 phi cells showed very little variation. In a typical
      experiment, the uptake of these photosensitizers by HL60 phi cells was four to
      five times higher than the uptake by noninduced HL60 cells. In addition to the
      fluorometric assay employed in most of the experiments, cellular concentration of
      A1PcS4 was determined by measurement of elementary aluminum using atomic
      absorption spectroscopy.

PMID- 8284323
TI  - Non-nuclear damage and cell lysis are induced by UVA, but not UVB or UVC,
      radiation in three strains of L5178Y cells.
AB  - The potential to induce non-nuclear changes in mammalian cells has been examined
      for (1) UVA1 radiation (340-400 nm, UVASUN 2000 lamp), (2) UVA+UVB (peak at 313
      nm) radiation (FS20 lamp), and (3) UVC (254 nm) radiation (G15T8 lamp). The
      effects of irradiation were monitored in vitro using three strains of L5178Y (LY)
      mouse lymphoma cells that markedly differ in sensitivity to UV radiation.
      Comparisons were made for the effects of approximately equitoxic fluences that
      reduced cell survival to 1-15%. Depending on the cell strain, the fluences ranged
      from 830 to 1600 kJ/m2 for the UVASUN lamp, 75 to 390 J/m2 for the FS20 lamp and
      3.8 to 17.2 J/m2 for the G15T8 lamp. At the exposure level used in this study,
      irradiation with the UVASUN, but not the FS20 or G15T8, lamp induced a variety of
      non-nuclear changes including damage to cytoplasmic organelles and increased
      plasma membrane permeability and cell lysis. Cell lysis and membrane
      permeabilization were induced by the UVA1 emission of the UVASUN lamp, but not by
      its visible+IR components (> 400 nm). The results show that the plasma membrane
      and other organelles of LY cells are highly sensitive to UVA1 but not to UVB or
      UVC radiation. Also UVA1, but not UVB or UVC radiation, causes rapid and
      extensive lysis of LY cells. In conclusion, non-nuclear damage contributes
      substantially to UVA cytotoxicity in all three strains of LY cells.

PMID- 8284324
TI  - The treatment of mastocytoma cells with 8-methoxypsoralen and long-wavelength
      ultraviolet radiation enhances cellular immunogenicity: preliminary results.
AB  - Evidence for the increased immunogenicity of mastocytoma cells (P815) treated
      with 8-methoxypsoralen (8-MOP) and long-wavelength ultraviolet radiation (UVA) is
      presented. A highly tumorigenic clone (P1) became much less tumorigenic (tum-)
      after repetitive phototreatments with 8-MOP (16 ng/mL) and UVA (1 J/cm2). The
      yield of tum- clones was proportional to the number of phototreatments. In a
      pilot study in which P1 cells were treated with three successive rounds of 8
      MOP/UVA, one clone out of 73 was tum-. In a second series of experiments, the P1
      cells were treated 10 times and 4 out of 100 clones were much less tumorigenic.
      When some of the tum- clones were administered intraperitoneally to DBA/2 mice,
      significant protection against challenge with the original P1 clone was observed.
      In addition, the transfer of immune cells from tum(-)-treated mice allowed the
      transfer of resistance to other tum- clones to immunosuppressed mice (650 rad).
      These results are consistent with earlier literature showing the potent mutagen,
      N-methyl-N'-nitrosoguanidine, led to mutations in P1 that altered the expression
      of new surface antigens, which stimulated the murine immune system such that
      there was also cross recognition of shared antigens on untreated P1 cells used to
      challenge the immunized mice. The increased immunogenicity that resulted from the
      less mutagenic 8-MOP/UVA treatment may arise by a similar mechanism and may be
      responsible in part for the efficacy of 8-MOP/UVA photochemotherapy for the
      treatment of cutaneous T cell lymphoma.

PMID- 8284325
TI  - Protection against ultraviolet B radiation-induced effects in the skin of SKH-1
      hairless mice by a polyphenolic fraction isolated from green tea.
AB  - In prior studies we and others have shown that oral feeding of a polyphenolic
      fraction isolated from green tea (GTP) or water extract of green tea affords
      protection against ultraviolet B (UVB) radiation-induced carcinogenesis in SKH-1
      hairless mice (Wang et al., Carcinogenesis 12, 1527-1530, 1991). It is known that
      exposure of murine skin to UVB radiation results in cutaneous edema, depletion of
      the antioxidant-defense system and induction of ornithine decarboxylase (ODC) and
      cyclooxygenase activities. In this study we assessed the protective effect of GTP
      on these UVB radiation-caused changes in murine skin. Oral feeding of 0.2% GTP
      (wt/vol) as the sole source of drinking water for 30 days to SKH-1 hairless mice
      followed by irradiation with UVB (900 mJ/cm2) resulted in significant protection
      against UVB radiation-caused cutaneous edema (P < 0.0005) and depletion of the
      antioxidant-defense system in epidermis (P < 0.01-0.02). The oral feeding of GTP
      also resulted in significant protection against UVB radiation-caused induction of
      epidermal ODC (P < 0.005-0.01) and cyclooxygenase activities (P < 0.0001) in a
      time-dependent manner. Our data indicate that the inhibition of UVB radiation
      caused changes in these markers of tumor promotion in murine skin by GTP may be
      one of the possible mechanisms of chemopreventive effects associated with green
      tea against UVB-induced tumorigenesis. The results of this study suggest that
      green tea, specifically polyphenols present therein, may be useful against
      inflammatory responses associated with the exposure of skin to solar radiation.

PMID- 8284326
TI  - Analyzing the red-shift characteristics of azulenic, naphthyl, other ring-fused
      and retinyl pigment analogs of bacteriorhodopsin.
AB  - Prompted by the near infrared-absorbing properties of some of the azulenic
      bacteriorhodopsin (bR) analogs, we have analyzed their absorption characteristics
      along with 11 new related ring-fused analogs and the corresponding Schiff bases
      (SB) and protonated Schiff bases (PSB). The following three factors are believed
      to contribute to the total red shift of each of the pigment analogs (sigma RS):
      perturbation of the basic chromophore (SB shift, delta SB), protonation of the SB
      (PSB shift, PSBS) and protein perturbation (the opsin shift, OS). For each
      factor, effects of structural modifications were examined. For the red-shifted
      pigments, percent OS has been suggested as an alternate way of measuring protein
      perturbation. Computer-simulated chromophores provided evidence against any
      explanation involving altered shapes of the binding pocket as a major cause for
      absorption differences. Implications of the current bR results on preparation of
      further red-shifted bR and possible application to visual pigment analogs are
      discussed.

PMID- 8284327
TI  - Role of hydroxyl-bearing amino acids in differentially tuning the absorption
      spectra of the human red and green cone pigments.
AB  - The human red and green cone pigments differ at either 15 or 16 amino acids,
      depending upon which polymorphic variants are compared. Seven of these amino acid
      differences involve the introduction or removal of a hydroxyl group. One of these
      differences, a substitution of alanine for serine at position 180, was found
      previously to produce a 5 nm blue shift. To determine the role of the remaining
      six hydroxyl group differences in tuning the absorption spectra of the human red
      and green pigments, we have studied six site-directed mutants in which single
      amino acids from the green pigment have been substituted for the corresponding
      residues in the red pigment. Blue shifts of 7 and 14 nm were observed upon
      substitution of phenylalanine for tyrosine at position 277 and alanine for
      threonine at position 285, respectively. Single substitutions at positions 65,
      230, 233, and 309 produced spectral shifts of 1 nm or less. These data are in
      good agreement with a model based upon sequence comparisons among primate
      pigments and with the properties of site-directed mutants of bovine rhodopsin.
      Nonadditive effects observed in comparing the absorption spectra of red-green
      hybrid pigments remain to be explained.

PMID- 8284328
TI  - Aggregation of 2,3-dihydroxy-etiochlorin I. An amphiphilic model compound for
      photodynamic therapy and green heme d.
AB  - The crystal structure of 2,3-dihydroxy-etiochlorin I has been determined to
      obtain information on its aggregation behavior. Cis-dihydroxychlorins serve as
      model compounds for green heme d and show promising photonecrotic activity in
      photodynamic therapy. The compound shows strong aggregation in the solid state
      facilitated by intramolecular hydrogen bonding between one hydroxy group and
      pyrrole nitrogens of neighboring molecules. This novel type of aggregation leads
      to chain-type aggregates in the crystal. The title compound 4 crystallized in the
      monoclinic space group Ia (Z = 4) with unit cell dimensions a = 9.902(4) A, b =
      26.430(9) A, c = 10.823(5), beta = 104.47(3) A, V = 2743(2) A3. The structure was
      refined to an R-value of 0.097 on the basis of 1150 reflections with F > 4.0
      sigma (F) (130 K).

PMID- 8284329
TI  - Nuclear factor kappa B binding activity in mouse L1210 cells following photofrin
      II-mediated photosensitization.
AB  - Clinical photodynamic therapy (PDT) uses the photosensitizer photofrin II to
      produce singlet molecular oxygen and other reactive oxygen intermediates for
      localized tumor tissue cytotoxicity. In this report, we show that PDT enhances
      the DNA binding activity of nuclear factor kappa B (NF kappa B), a transactivator
      of cytokine gene expression. Photosensitization following a 16 h incubation of
      photofrin II induced NF kappa B binding activity in mouse leukemia L1210 cells 10
      fold above that observed in exponentially growing cultures. Serum starvation, as
      well as drug-alone and light-alone controls, elevated basal NF kappa B binding
      activity two- to three-fold. Upstream stimulatory factor binding activity was not
      modulated by any of the cell treatments and was used to standardize gel mobility
      shift data. This study identifies porphyrin-mediated PDT as an inducer of NF
      kappa B binding activity, extending recent findings that NF kappa B activation is
      a general response to oxidative stress.

PMID- 8284330
TI  - Developmental observation, multiple models of the mind, and the therapeutic
      relationship in psychoanalysis.
AB  - This overview of the therapeutic relationship in psychoanalysis utilizes a
      sampling of findings of infant observational research to illuminate issues in the
      evolving technique of psychoanalysis. The therapeutic relationship is followed
      schematically through the course of a treatment, from initial contact through
      termination, and the gradual shift of psychoanalytic technique toward an
      interactional view of the psychoanalytic situation is noted. During the middle
      phase, some areas of current controversy in psychoanalysis are discussed, along
      with views on the multiple theoretical models currently available for organizing
      psychoanalytic data and for gaining clinical access for analytic work.

PMID- 8284331
TI  - Analytic interaction: conceptualizing technique in light of the analyst's
      irreducible subjectivity.
AB  - Every aspect of an analyst's clinical activity is determined in part by his or
      her personal psychology. The implications for our theory of technique of taking
      the analyst's subjectivity fully into account--which we have tended not to do-
      are discussed.

PMID- 8284332
TI  - Early sexual abuse and nightmares in the analysis of adults.
AB  - An examination of the nightmares of four adults in analysis who had been sexually
      abused as children revealed a characteristic distortion of the body
      representation as it appeared in the manifest content of the dream. The authors
      believe that childhood sexual trauma has profound and pervasive effects on the
      development and consolidation of the body image. Experienced as a grave assault
      on body integrity and function, it mobilizes primitive anxieties and specific
      genital anxieties, resulting in distortion, fragmentation, or disintegration of
      the body representation. The frequently observed multiple somatization of victims
      of sexual abuse is attributable to such a damaged and persecutory body
      representation.

PMID- 8284333
TI  - The personal dimension and management of the supervisory situation with a special
      note on the parallel process.
AB  - This paper focuses on the vicissitudes of the supervisor/supervisee relationship
      and on the personal impact of supervision on the candidate. Conflicts within the
      supervisory situation and their potential intrusion into the learning process are
      discussed. The supervisee's character as a limiting factor and some of the
      dynamics of the parallel process are considered as well. A number of vignettes
      illustrate the problems involved and some possible remedies.

PMID- 8284334
TI  - An unusual relationship: the final encounter of Picasso and Matisse.
AB  - Picasso and Matisse renewed their relationship in 1946 as the aging Matisse
      approached death. Picasso, ordinarily contemptuous of others and indifferent to
      their needs, revealed a markedly different attitude toward Matisse, whom he
      admired and whose affection and approbation he sought. The roots of Picasso's
      attitude are traced to his morbid concern about bodily deterioration and fear of
      death. Matisse, apparently serene in his confrontation with approaching death,
      represented an ideal to Picasso, a hoped-for remedy for anxiety, a confident
      paternal representation so unlike his father. Freud's view of death, poetically
      expressed in his paper, "On Transience," is a model for contrasting Picasso's
      "revolt . . . against mourning" with Matisse's sense of symbolic immortality.

PMID- 8284335
TI  - Rodman Gilder 1918-1993.

PMID- 8284336
TI  - Avoiding research in consultation-liaison psychiatry.

PMID- 8284337
TI  - Secondary prevention of ischemic heart disease. The case for aggressive
      behavioral monitoring and intervention.
AB  - The hierarchy of evidence for arguing causality of a disease by any factor
      consists of epidemiological and, ultimately, treatment studies. The application
      of these criteria to chronic negative emotion as a risk factor for ischemic heart
      disease (IHD) is relatively new. However, controlled prospective evidence now
      indicates that anger, depression, and anxiety may play a major role in the
      genesis of IHD. And the strongest form of evidence, a controlled clinical trial
      that used randomly assigned subjects, exists, implicating anger as a strong
      predictor in the development of IHD. Resistance to the utility of this avenue of
      care is not based on evidence alone because widely accepted risk factors and/or
      treatment modalities often have less persuasive evidence, or less powerful
      effects, than do the emotional factors. Rather, such resistance is largely due to
      "paradigmatic scotomata"--conceptual difficulties for those not familiar with
      biopsychosocial research. Routine psychometric screening of IHD patients may
      provide a cost-effective means of alerting cardiologists and internists to the
      relatively high levels of distress among their patients.

PMID- 8284338
TI  - Recurrent abdominal pain in child patients seen at a pediatric gastroenterology
      clinic. Observations of 50 children and their families.
AB  - Recurrent abdominal pain is a common patient complaint in general pediatric and
      gastroenterology clinics. Various psychiatric problems have been noted in the
      children, adolescents, and parents of children who present with nonorganic
      recurrent abdominal pain. This article reviews the stressors, psychopathology,
      and biopsychosocial treatment of 50 patients with recurrent abdominal pain who
      were referred from a pediatric gastroenterology clinic to their psychiatric
      consultant over a 3-year period (1987-1990). The salient literature is also
      reviewed and thoughts for future research are outlined.

PMID- 8284339
TI  - Overlooked physical diagnoses in chronic pain patients involved in litigation.
AB  - This study followed the course of 60 chronic pain patients, from referral to a
      pain diagnostic center through the formulation of complete discharge diagnoses.
      The most common referral "diagnoses" were really descriptions or vague
      explanations, such as "chronic pain," "psychogenic pain," "cervical strain," or
      "lumbar strain." The most commonly missed diagnoses were 1) myofascial disease,
      2) facet disease, 3) peripheral nerve entrapment, 4) radiculopathy, and 5)
      thoracic outlet syndrome. Seventy percent of the laboratory studies ordered by
      the clinic had significant abnormalities. The authors determined that the overall
      rate of inaccurate or incomplete diagnosis at referral was 66.7%.

PMID- 8284340
TI  - Association of baseline neuropsychological function and progression of illness
      over 4 years in HIV-seropositive individuals.
AB  - The authors conducted a study to examine the association between
      neuropsychological markers of central nervous system impairment and systemic
      human immunodeficiency virus (HIV) disease progression in a sample of 64 HIV
      positive asymptomatic patients who were followed for a median of 45.6 months.
      Patients with poorer baseline scores on the Halstead-Reitan Trail-Making A
      neuropsychological test developed HIV-related systemic symptoms earlier over the
      study period than patients with the higher scores on the same test (P < 0.05).
      Subclinical neuropsychological dysfunction in otherwise asymptomatic HIV-infected
      individuals may be a harbinger of progressive HIV-related immunologic
      dysfunction.

PMID- 8284341
TI  - Maternal distress and discrepancy in reports of psychopathology in chronically
      ill children.
AB  - This article focuses on the relation between maternal distress and mother-child
      discrepancy in reports of child psychopathology, as assessed by a standardized
      structured interview. The sample includes 92 chronically ill children (mean age
      +/- SD = 12.5 +/- 2.7 years). Agreement between mother and child on the presence
      of any child psychiatric diagnosis was low. Maternal distress was correlated with
      the number of disorders identified by the mother but not with those identified by
      the child. Maternal distress was significantly higher in the mothers who
      identified a disorder but whose children did not. Choice of informant and
      maternal distress are significant factors in the evaluation of psychopathology.

PMID- 8284342
TI  - Neurobehavior rounds. Their role in promoting psychiatric liaison in a neurology
      inpatient unit.
AB  - A joint neurobehavior conference was established utilizing the models of
      Lipowski's Montreal conference and Geschwind's aphasia and neurobehavior rounds
      at the Boston VA Hospital in 1991. The authors report on the usefulness of this
      conference in promoting the goals of psychiatric consultation and liaison on a
      neurology inpatient unit, specifically on patient care, education, and
      collegiality. The value of the multidisciplinary approach in solving complex
      neuropsychiatric problems is also discussed.

PMID- 8284343
TI  - Significance of stuffed animals at the bedside and what they can reveal about
      patients.

PMID- 8284344
TI  - Partial complex status epilepticus in a lithium-toxic patient.

PMID- 8284345
TI  - Conversion hysteria and dominant hemisphere lesions.

PMID- 8284346
TI  - Electroconvulsive therapy for depression in a liver transplant patient.

PMID- 8284347
TI  - Isoniazid-induced hallucinosis: response to pyridoxine.

PMID- 8284348
TI  - Thyrotoxicosis in a depressed patient on L-triiodothyronine.

PMID- 8284349
TI  - The structure of branched DNA species.

PMID- 8284350
TI  - Interrelations of bioenergetic and sensory functions of the retinal proteins.
AB  - Rhodopsins are intrinsic membrane retinal-containing proteins composed of 7
      hydrophobic alpha-helical transmembrane columns and hydrophilic sequences of
      various length connecting the helices and localized at N- and C-ends of the
      polypeptide. The chromophore (retinal) forms a Schiff base with a lysine residue
      in the middle part of the last alpha-helix. Absorption of a photon results in
      isomerization of retinal which gives rise to a conformational change in the
      protein moiety. Rhodopsins can be involved in two entirely different types of
      activities, i.e. ion pumping and photosensing. Recent observations concerning the
      pumping and sensory mechanisms allowed both these events to be explained in terms
      of one and the same unitary concept, which postulates the formation of a
      hydrophilic cleft in the hydrophobic part of the protein molecule as a crucial
      step in energy conservation and photosensing.

PMID- 8284351
TI  - Nonlinear dynamics of biopolymers: theoretical models, experimental data.

PMID- 8284352
TI  - The diagnosis and staging of primary lung cancer.
AB  - The controversy surrounding the diagnosis and staging of the patient with primary
      lung cancer is reviewed in this article. Three basic algorithmic approaches to
      the problem are presented, with recommendations for both the theoretic and
      practical approaches to staging.

PMID- 8284353
TI  - Magnetic resonance staging of neoplasms of the uterus.
AB  - The treatment of patients with uterine neoplasms may be significantly altered by
      the stage of disease at the time of diagnosis. A noninvasive and accurate means
      of staging these tumors is therefore desirable. This article discusses the
      magnetic resonance imaging techniques and findings that are essential for the
      accurate staging of uterine neoplasms. The imaging findings are presented
      following a discussion of the histopathologic findings, clinical presentation,
      diagnosis and staging, pathways of tumor spread, and treatment of each neoplasm.
      A comparison of magnetic resonance and other imaging techniques is also provided.

PMID- 8284354
TI  - Radiologic staging of thoracoabdominal tumors in childhood.
AB  - Thoracoabdominal tumors of childhood include a pathologically diverse spectrum of
      neoplasms. Improved survival for many of these once lethal malignancies reflects
      current multimodality approaches to treatment based on the combined experience of
      specific tumor study groups. The choice of surgery, chemotherapy, and/or
      radiation depend on accurate clinical and radiologic staging based on
      determination of tumor extent and the feasibility of surgical resection. Advanced
      cross-sectional and scintigraphic imaging techniques have enhanced the accuracy
      of radiologic assessment and staging. Established pathologic patterns of local
      extension and more distant dissemination, as well as the relative sensitivity and
      specificity of applicable imaging modalities determine radiologic approaches to
      radiologic staging of specific neoplasms.

PMID- 8284355
TI  - Neoplasms of the upper gastrointestinal tract.
AB  - Neoplasms of the upper gastrointestinal tract are generally detected by barium
      studies or endoscopy. Computed tomography remains the primary imaging modality
      for staging. Magnetic resonance imaging and endoscopic ultrasonography may also
      play an increasing role in evaluating these tumors.

PMID- 8284356
TI  - Staging of musculoskeletal tumors.
AB  - Staging of musculoskeletal neoplasms is important for planning chemotherapy and
      surgical procedures. Accurate staging has increased in importance with
      advancements in limb salvage procedures. This article outlines concepts,
      techniques, and potential problems with staging of neoplasms. It is important to
      remember that biopsy should be preformed after consultation with an orthopedic
      surgeon specialized in tumor surgery.

PMID- 8284357
TI  - Radiologic diagnosis and staging of head and neck squamous cell carcinoma.
AB  - The predominant extracranial head and neck cancer in adults is squamous cell
      carcinoma. The purpose of this article is to discuss the radiographic evaluation
      of these patients with computed tomography (CT) or magnetic resonance (MR)
      imaging prior to therapeutic intervention. Specific focus is given to the
      efficacy of CT and MR imaging, as an adjunct to clinical staging, for evaluation
      of the primary tumor, and metastatic adenopathy. MR imaging, because of its
      improved soft tissue contrast and multiplanar capability, is probably superior to
      CT for evaluation of the primary tumor in patients with squamous cell carcinoma.
      CT, however, remains the gold standard for identifying metastatic adenopathy and
      in most institutions remains the study of choice for evaluating this patient
      population.

PMID- 8284358
TI  - Radiologic diagnosis, staging, and follow-up of adult central nervous system
      primary malignant glioma.
AB  - Glioma represents the most common primary intra-axial brain tumor. Currently,
      magnetic resonance (MR) imaging is the study of choice for the radiographic
      evaluation of patients with primary central nervous system glioma prior to and
      following therapeutic intervention. Computed tomography and MR imaging are
      frequently used for stereotactic biopsy and mapping. MR spectroscopy and/or
      thallium-201 single photon emission computed tomography may prove helpful in
      differentiating recurrent malignancy from radiation-induced necrosis.

PMID- 8284359
TI  - Staging colorectal carcinoma.
AB  - Colorectal cancers are the second most common tumor in the United States and the
      most common gastrointestinal cancer. Preoperative staging with computed
      tomography, magnetic resonance imaging, and endorectal ultrasonography has some
      limitations. Their routine use has not been established. Endorectal
      ultrasonography may prove valuable in patients with rectal tumors. Computed
      tomography is the recommended procedure for follow-up imaging in colorectal
      cancer patients.

PMID- 8284360
TI  - Liver tumor imaging. Current concepts.
AB  - With the increasing availability of curative surgical techniques for primary and
      secondary hepatic neoplasms, the tasks for clinical imaging of patients suspected
      of having liver cancer have become more exacting. Detection of tumor,
      differential diagnosis of individual nodules, and mapping the anatomic extensions
      of malignant disease are now required routinely. The most sensitive imaging
      techniques are computed tomography and arterial portography and intraoperative
      sonography, but because of their invasiveness, there are reserved exclusively for
      cancer staging. For primary screening, magnetic resonance imaging is increasingly
      preferred over computed tomography because of its superiority in discriminating
      hemangiomas and cysts from metastases without the need for iodinated contrast
      material.

PMID- 8284361
TI  - The imaging evaluation of renal cell carcinoma: diagnosis and staging.
AB  - Computed tomography plays the dominant role in the pretreatment evaluation of
      renal carcinomas. For detection, definition (staging), and determination of
      resectability or recurrence, both computed tomography with dynamic intravenous
      contrast enhancement and magnetic resonance imaging with Gadolinium-based
      contrast enhancement may offer all the cross-sectional imaging information
      required prior to institution of appropriate therapy. Ultrasonography and color
      flow Doppler ultrasonography may offer unique information about tumor vascularity
      and major venous vascular involvement. An oncologic imaging approach that is
      based on tumor staging and classification for patients with real or suspected
      renal carcinoma is described.

PMID- 8284362
TI  - Radiologic staging of pancreatic adenocarcinoma.
AB  - Dynamic CT currently is the imaging modality of choice for staging of pancreatic
      carcinoma. It has an accuracy of 72% in predicting tumor resectability and an
      accuracy of virtually 100% in predicting tumor unresectability. However, it is
      important that the CT criteria of unresectability be defined for each individual
      institution. In some hospitals, extended pancreatectomy, including resection of
      involved major extrapancreatic vessels, contiguous solid or hollow organs, and
      regional lymph nodes, is performed for pancreatic carcinoma. Thus, these CT
      findings would not be considered to obviate surgical resection, whereas in other
      hospitals, surgeons consider tumor spread beyond the gland, particularly vascular
      involvement, as a contraindication for resection. It is also important to note
      that enlarged regional lymph nodes that would be included in the resection are
      not considered to be a CT criteria of unresectability when they occur as an
      isolated finding. MR imaging, EUS, and angiography have less significant roles
      compared with CT in the staging of pancreatic carcinoma; however, MR imaging and
      EUS can be valuable staging techniques in patients in whom an optimal dynamic
      contrast-enhanced CT cannot be obtained, although angiography now is indicated
      primarily to provide the surgeon with a vascular roadmap prior to resection or to
      evaluate patients in whom CT is equivocal.

PMID- 8284363
TI  - Neoplasms of the bladder, prostate, and testis.
AB  - As a group, carcinomas of the urinary bladder, prostate, and testis account for
      more than one third of all cancers occurring in men. Computed tomography is the
      imaging procedure of choice for postorchiectomy staging of testicular cancers.
      Transrectal ultrasonography and magnetic resonance imaging play important roles
      in the staging of prostate cancer. Magnetic resonance imaging, computed
      tomography, and transurethral ultrasonography are all capable of providing
      important information in the staging of bladder cancer. Carefully designed
      clinical trials will be needed to provide a sound scientific basis for guiding
      the judicious use of imaging tests for staging bladder and prostate cancer in the
      future.

PMID- 8284364
TI  - Computed tomography in spiral mode.

PMID- 8284365
TI  - Teaching your students to care.

PMID- 8284366
TI  - Non-surgical biopsy: providing a choice.

PMID- 8284367
TI  - Why continuing education?

PMID- 8284369
TI  - Technique detects hard-to-find cancers.

PMID- 8284368
TI  - QA through exception reporting.
AB  - All staff members are involved in the QA by exception process, empowering them to
      voice what is wrong with the system and giving them the opportunity to have an
      impact on improvement. Since the review of aspects of care is ongoing and all
      encompassing, it allows for continuous improvement. Other reviews will be
      required; however, this comprehensive method of assessment can add to the value
      of your QA program. It provides accurate measurements and positive direction
      while facilitating quality improvement.

PMID- 8284370
TI  - Radiography education's past ... and future. 1970.

PMID- 8284371
TI  - Achieving dose reduction in lumbar spine radiography.
AB  - Conventional lumbar spine examinations are performed by placing the patient in
      the supine position. The alternative prone position is less commonly used. In
      this study, researchers measured entrance skin exposure for both supine and prone
      positioning techniques and the radiation dose to the eyes, thyroid, ovaries,
      testes and bone marrow. Compared with the AP projection, the PA projection
      produced a moderately higher bone marrow dose (28%), but resulted in a slightly
      reduced dose (17%) to the thyroid and greatly reduced doses (200+%) to the eyes,
      ovaries, uterus and testes. The PA projection also produced an ESE 52% lower than
      the AP projection. Results suggest an advantage to using prone positioning for
      lumbar spine examinations.

PMID- 8284372
TI  - Assessing adequacy of mammographic image quality.
AB  - High-quality mammographic images enhance the radiologist's ability to interpret
      mammograms with high sensitivity for detecting abnormalities and high specificity
      for classifying lesions suspicious for malignancy. In addition to proper
      exposure, contrast, resolution, compression, and positioning, high-quality
      mammographic images must be accompanied by pertinent history and available
      comparison images. To avoid negating the benefits of technically ideal images,
      mammograms must be viewed under optimal viewing conditions. Constant attention to
      quality control, with every image evaluated for adherence to strict technical
      standards, is essential for maintaining image quality.

PMID- 8284373
TI  - Role of CT and CT-guided nodal biopsy in staging of prostatic cancer.

PMID- 8284374
TI  - Appropriate role of core breast biopsy in the management of probably benign
      lesions.

PMID- 8284375
TI  - Lymph node staging of localized prostatic carcinoma with CT and CT-guided fine
      needle aspiration biopsy: prospective study of 285 patients.
AB  - PURPOSE: To ascertain the reliability of computed tomography (CT) and CT-guided
      fine-needle aspiration biopsy (FNAB) in staging of lymph nodes in patients with
      locally confined prostatic carcinoma. MATERIALS AND METHODS: A total of 285
      patients were studied prospectively. FNAB was performed in 43 patients (15%) with
      lymph nodes suspect for metastasis on CT scans. FNAB findings were correlated
      with either the findings of the pathologic examination performed after lymph node
      dissection (LND) or the status of the lymph node at follow-up with CT after
      hormone therapy. RESULTS: The sensitivity, specificity, and accuracy of CT-guided
      FNAB were 77.8%, 100%, and 96.5%. If CT only had been performed, these results
      would have been 77.8%, 96.7%, and 93.7%. CT staging was false-negative in only 10
      patients, who had microscopic metastatic deposits in a solitary lymph node.
      CONCLUSION: Combined CT and FNAB is highly efficient for assessment of lymph node
      metastasis. Therefore, it could be considered an alternative to surgical or
      laparoscopic lymphadenectomy in patients scheduled for radical prostatectomy or
      curative radiation therapy.

PMID- 8284376
TI  - MR imaging of prostate cancer with an endorectal surface coil technique:
      correlation with whole-mount specimens.
AB  - PURPOSE: To evaluate the diagnostic accuracy of magnetic resonance (MR) imaging
      in staging prostate cancer with an endorectal surface coil technique. MATERIALS
      AND METHODS: The authors prospectively evaluated MR images obtained with an
      endorectal surface coil from 70 consecutive patients with known prostate cancer.
      Gadopentetate dimeglumine was administered to 40 patients. Multiple sequences
      were used, including conventional and fast spin echo, with and without fat
      suppression. The readers were blinded to the MR findings unless bone or nodal
      metastasis was present. MR images were compared with whole-mount sections.
      RESULTS: The prospective staging accuracy for MR imaging was 51% (36 of 70
      patients). Stage B disease was present in 27 patients (38%), stage C in 42 (60%),
      and stage D in one (1%). The retrospective staging accuracy was 67% (47 of 70
      patients). Of the 42 patients with stage C disease, positive surgical margins
      were present in 36 (85%). Gadopentetate dimeglumine did not help detect or stage
      tumors. CONCLUSION: Further studies must be performed to determine the role of
      endorectal coil MR imaging in the staging of prostate cancer.

PMID- 8284377
TI  - Ovarian masses: can benign and malignant lesions be differentiated with color and
      pulsed Doppler US?
AB  - PURPOSE: To determine whether color and pulsed Doppler ultrasound (US) can be
      used to differentiate benign from malignant ovarian masses. MATERIALS AND
      METHODS: Forty-four ovarian masses identified with sonography in 40 patients were
      confirmed at surgery (n = 35) or followed up to resolution with US (n = 9). Color
      and pulsed Doppler US were used to calculate the lowest pulsatility index (PI)
      and resistance index (RI) for each mass. RESULTS: Color Doppler US enabled
      detection of arterial flow in 24 of 36 benign masses and six of eight malignant
      masses. PI was lower in malignant masses than in benign masses (P = .002), as was
      RI (P = .001). Both indexes demonstrated overlap between benign and malignant
      masses; therefore, no cutoff value for either index had both high sensitivity and
      high specificity for malignancy: For PI cutoff of 1.0, sensitivity and
      specificity were 100% and 46%, respectively; for RI cutoff of 0.4, 50% and 96%.
      CONCLUSIONS: While PI and RI tend to be lower in malignant ovarian masses,
      neither index can be used reliably to differentiate benign from malignant
      lesions. In addition, lack of detectable flow by means of color Doppler US does
      not exclude ovarian malignancy.

PMID- 8284378
TI  - Ovarian torsion: CT and MR imaging appearances.
AB  - PURPOSE: To describe the features of twisted ovarian tumors on computed
      tomographic (CT) scans and magnetic resonance (MR) images. MATERIALS AND METHODS:
      The CT scans, MR images, clinical records, and histopathologic findings in 10
      patients with surgical proof of a twisted adnexal tumor were retrospectively
      evaluated. RESULTS: The most common findings on MR images were nonspecific:
      deviation of the uterus to the twisted side (n = 9), engorged blood vessels on
      the twisted side (n = 6), a small amount of ascites (n = 5), and obliteration of
      fat (n = 4). The following characteristics were seen only in the five patients
      with hemorrhagic infarction: (a) a protrusion of the lesion on the twisted side
      to which the uterus was continuous or engorged blood vessels converged (n = 5);
      (b) thick, straight blood vessels that draped around the lesion (n = 2); (c)
      distinct hematoma (n = 2); and (d) complete absence of enhancement (n = 3).
      CONCLUSION: Three findings (a, b, and d) seem to be diagnostic of the twisted
      adnexal tumor and may facilitate prompt surgical intervention at examination with
      MR imaging or CT.

PMID- 8284379
TI  - Diabetic nephropathy: evaluation with renal duplex Doppler US.
AB  - PURPOSE: To compare Doppler ultrasonography (US) with conventional clinical and
      laboratory tests in evaluation of diabetic renal disease. METHODS: Ninety-eight
      patients with diabetes mellitus underwent renal Doppler (resistive index [RI]
      measurement) US examination. US data were compared with clinical variables and
      follow-up data. RESULTS: Thirty-four diabetic patients without nephropathy had a
      mean RI of 0.62 +/- 0.09, which was not significantly different from the mean RI
      of 0.64 +/- 0.09 in 23 patients with early diabetic nephropathy. Patients with
      established nephropathy had a mean RI of 0.83 +/- 0.11, which was significantly
      (P < .001) higher than in the other two groups. Renal RI correlated highly with
      serum creatinine concentration (r = .64) and creatinine clearance rate (r = .80).
      An elevated RI (> or = 0.70) was associated with impaired renal function,
      increased proteinuria at 24 hours, and poor outcome. Absent diastole (RI = 1.0),
      observed in 7% of patients, was an ominous sign: Five of seven patients underwent
      dialysis or transplantation shortly after US. CONCLUSION: RI is typically
      elevated in established nephropathy but is often normal in the early clinical
      stages of disease. Renal Doppler US provides an accurate indication of renal
      function in diabetic nephropathy but does not offer a great advantage over
      conventional tests.

PMID- 8284380
TI  - Detection of heart calcification with electron beam CT: interobserver and
      intraobserver reliability for scoring quantification.
AB  - PURPOSE: To assess interobserver and intraobserver reliability of three
      quantitative measures of coronary artery calcium burden: calcium "score," number
      of calcified lesions, and calcified area. MATERIALS AND METHODS: Electron beam
      computed tomographic (CT) scanning was used in a series of 25 patients to detect
      coronary artery calcification. Scan results were reviewed for quality by a
      radiologist, then scored by two radiologic technologists and by another
      radiologist. RESULTS: Many interobserver and intraobserver disagreements were
      noted on a lesion-by-lesion basis. Since most disagreements involved very small
      lesions, however, their impact was negligible for all three measures of calcium
      burden. CONCLUSION: It is not useful for more than one observer to independently
      score a single CT examination obtained to detect cardiac calcification, even when
      the arteries are heavily calcified.

PMID- 8284381
TI  - Is 300 msec too long for cardiac MR imaging? Feasibility study demonstrating
      changes in left ventricular cross-sectional area with use of single-shot
      turboFLASH imaging.
AB  - PURPOSE: To assess the feasibility of demonstrating cardiac motion with 313.6
      msec single-shot turbo-fast low-angle shot magnetic resonance imaging. MATERIALS
      AND METHODS: Effects of motion on single-shot images were evaluated with a
      phantom moving at known velocity. Single-shot images were obtained in eight
      healthy volunteers and four cardiac patients and compared with conventional cine
      images. RESULTS: The moving phantom was visualized at the location where zero
      phase-encoded data were sampled. When the velocity was within the physiologic
      range of left ventricular wall motion (< 11 cm/sec), the full width at half
      maximum of the object on a 64 x 64-matrix image with a 4.9-msec repetition time
      was comparable with that of a stationary phantom. The left ventricular cross
      sectional area determined with single-shot imaging showed good correlation with
      results of conventional cine imaging (r = .96) in healthy volunteers. CONCLUSION:
      Single-shot imaging can be used for simple and quick assessment of cardiac
      function.

PMID- 8284382
TI  - MR angiography of the pelvis with variable velocity encoding and a phased-array
      coil.
AB  - PURPOSE: To evaluate the feasibility of an automated variable velocity-encoding
      sequence and improve the signal-to-noise ratio (S/N) on magnetic resonance
      angiograms with use of phase contrast and a pelvic phased-array coil. MATERIALS
      AND METHODS: Three cardiac-gated, two-dimensional (2D), phase-contrast (PC)
      sequences were evaluated in 10 healthy subjects. A 2D gated PC sequence with
      variable velocity encoding (velocity-optimized phase contrast [VOPC]) was
      compared with gated 2D PC sequences performed with high or low constant velocity
      encoding. S/Ns in VOPC images obtained with a pelvic phased-array coil were
      compared with those in VOPC images obtained with a body coil. RESULTS: Two
      blinded readers preferred VOPC for simultaneous display of large and small blood
      vessels in one acquisition compared with constant low (P = .0105) and high (P =
      .0067) velocity encoding and for overall image interpretation. VOPC images
      obtained with the pelvic coil had a 68%-100% better S/N compared with those
      obtained with the body coil. CONCLUSION: Use of a phased-array coil and variable
      velocity encoding improves depiction of segmental vascular anatomic structures of
      the pelvis.

PMID- 8284383
TI  - Renal artery blood flow: quantitation with phase-contrast MR imaging with and
      without breath holding.
AB  - PURPOSE: To compare the accuracy of 16-frame cine phase-contrast (PC) magnetic
      resonance (MR) imaging with those of two breath-hold PC techniques in the
      measurement of renal artery blood flow. MATERIALS AND METHODS: In vitro flow
      measurements were performed in a segment of harvested human artery embedded in
      gel. For the cine PC acquisition, respiratory motion was simulated. In eight
      subjects with recently obtained para-amino-hippurate-clearance renal blood flow
      data, renal artery flow measurements were subsequently performed with two breath
      hold imaging techniques and with cine PC imaging during shallow respiration.
      RESULTS: Breath-hold sequences were significantly more accurate than conventional
      cine PC sequences both in vitro (P < .005) and in vivo (P < .05). Cine PC imaging
      tended to overestimate flow (in vivo mean, 24.47% +/- 9.94), reflecting
      artifactual enlargement of the apparent vessel size. CONCLUSION: Reliable blood
      flow measurements in the renal artery are possible with breath-hold PC MR
      imaging.

PMID- 8284384
TI  - Palmaz stent in the treatment of central venous stenosis: safety and efficacy of
      redilation.
AB  - PURPOSE: To assess the safety and efficacy of redilation of central venous stents
      in a growing animal model. MATERIALS AND METHODS: Palmaz stents were placed in
      the inferior vena cava (IVC) in 18 newborn lambs. After 5 months, vena cavography
      was performed. Those animals in which growth of the IVC adjacent to the stent
      and/or neointimal hyperplasia had resulted in a stenosis were considered
      candidates for redilation. Repeat vena cavography, intravascular ultrasound, and
      histologic examination were performed at 2 or 6 months. RESULTS: A stenosis of >
      20% was demonstrated in 13 animals. Redilation was performed, and a 50% mean
      increase in stent diameter was achieved. There were no immediate complications.
      Late complications included nonocclusive laminar clot (n = 2), and a bar of
      tissue dividing but not occluding the caval lumen (n = 1). Moderate neointimal
      hyperplasia occurred in all stents. Stent compression (unrelated to redilation)
      occurred in seven animals. CONCLUSION: Palmaz stents can be redilated safely and
      effectively in an animal model of growing central veins.

PMID- 8284386
TI  - Idiopathic polyhydramnios: association with fetal macrosomia.
AB  - PURPOSE: To determine the relationship between idiopathic polyhydramnios and
      fetal macrosomia in the absence of maternal diabetes. MATERIALS AND METHODS:
      Idiopathic polyhydramnios was studied with ultrasound (US) in 99 consecutive
      normal fetuses of nondiabetic women. Birth weights and estimated fetal weights
      were compared with those of postnatal and prenatal control groups, respectively.
      RESULTS: The mean birth weight for the study (polyhydramnios) group was 3,771 g
      +/- 572 (standard deviation) compared with 3,476 g +/- 444 for the postnatal
      control group (P < .001). Birth weights in the 90th percentile or greater
      occurred in 28.2% of the study group versus 9.3% of the postnatal control group
      (P < .001) with a relative risk of 3.0 and a 95% confidence interval of 1.9, 4.9.
      The mean percentile of estimated fetal weight obtained with US was also
      significantly greater for the study group (79.3 +/- 23.7) than for the prenatal
      control group (51.5 +/- 32.7) (P < .001). CONCLUSION: Idiopathic polyhydramnios
      is associated with large-for-gestational-age fetuses and macrosomia independent
      of maternal diabetes.

PMID- 8284385
TI  - Symptomatic hepatic cysts: percutaneous drainage and sclerosis.
AB  - PURPOSE: To evaluate the authors' experience with treatment of symptomatic
      hepatic cysts by means of percutaneous catheterization and sclerosis. MATERIALS
      AND METHODS: Twenty patients with 24 symptomatic hepatic cysts underwent
      percutaneous drainage and sclerosis. Ten patients had polycystic disease, and 10
      had solitary cysts. Sclerosants used were alcohol, tetracycline, doxycycline, or
      a combination. RESULTS: Twenty-one of 24 cysts in 17 of 20 patients were treated
      successfully. Treatment was unsuccessful in three patients: one patient with
      innumerable medium-size and small cysts, one patient in whom only a needle was
      inserted (no catheter), and one patient with a cystic metastasis (rather than a
      simple cyst) that recurred. Complications included pleural effusion in two
      patients and secondary infection in one patient. The range of blood alcohol
      levels was 0-0.8 mg%. CONCLUSION: Percutaneous catheter drainage with sclerosis
      is an effective method of therapy for symptomatic hepatic cysts; careful patient
      selection is essential for proper therapy.

PMID- 8284387
TI  - Pediatric knee MR imaging: pattern of injuries in the immature skeleton.
AB  - PURPOSE: To evaluate the frequency of various cartilaginous and ligamentous knee
      injuries with magnetic resonance (MR) imaging in a large pediatric population.
      MATERIALS AND METHODS: The authors reviewed 104 consecutive MR imaging studies
      acquired in patients 4-18 years of age with open physes. Frequency of various
      injuries was compared by using a chi 2 test. The frequency of each injury was
      compared with published adult data by using the Student t test. Arthroscopic
      follow-up in 30 patients was used to calculate sensitivity and specificity.
      RESULTS: The medial meniscus was found to be injured more frequently than the
      lateral meniscus or the anterior cruciate ligament (ACL). Both menisci were
      injured less frequently than in adults. Sensitivity and specificity of MR imaging
      for meniscal tears were 83% and 95%, respectively, and for ACL tears were 64% and
      94%, respectively. CONCLUSIONS: These results show that medial meniscal tears are
      the most common cartilaginous or ligamentous injury in children and adolescents.
      The frequency of specific injuries, however, is different from that in adults.

PMID- 8284388
TI  - Juvenile rheumatoid arthritis of the knee: evaluation with US.
AB  - PURPOSE: To evaluate the value of ultrasound (US) in assessing joint inflammation
      in patients with juvenile rheumatoid arthritis (JRA) of the knee. MATERIALS AND
      METHODS: US scans obtained in 36 children (mean age, 8 years) with JRA of the
      knee were compared with those obtained in 30 healthy children. RESULTS: Changes
      in synovial membrane (synovial thickness), presence of fluid in the suprapatellar
      bursa, and alterations in the contour (blurring) of the articular cartilage
      showed statistically significant differences between JRA patients and control
      subjects. US was more sensitive than physical examination for detecting a minimal
      amount of intra-articular fluid in 21% of JRA-affected knees with no clinical
      evidence of active disease. CONCLUSION: US is a simple, rapid, inexpensive, and
      accurate method for assessing joint inflammation in patients with JRA of the
      knee.

PMID- 8284389
TI  - Three-dimensional sonographic evaluation of developmental dysplasia of the hip:
      preliminary findings.
AB  - PURPOSE: To determine the value of three-dimensional (3D) sonography in the
      evaluation of developmental dysplasia of the hip. MATERIALS AND METHODS: 3D
      reconstruction and section analysis were performed on 38 data acquisitions
      obtained in nine patients with a clinical diagnosis of developmental dysplasia of
      the hip. Data were obtained mostly in the coronal plane, and section-analysis and
      3D volume reconstruction images were generated. RESULTS: Of the 32 image sets
      obtained in the coronal plane, the technical quality of 27 (84%) section-analysis
      images and 25 (78%) spatial-revolving images was judged to be satisfactory.
      CONCLUSION: In addition to permitting global visualization of the hip, 3D
      sonography offers imaging in the sagittal and craniocaudal projections, something
      no other modality can offer. 3D sonography can also demonstrate the relationship
      of the femoral head to the acetabulum and femoral head containment more
      thoroughly than does conventional sonography.

PMID- 8284390
TI  - Splenic enlargement in neonates during ECMO.
AB  - PURPOSE: To determine whether hepatosplenomegaly was a reproducible finding in
      seven neonates who were being treated with extracorporeal membrane oxygenation
      (ECMO) for respiratory failure. MATERIALS AND METHODS: The authors measured
      splenic and hepatic dimensions with ultrasound (US) at the time ECMO was
      initiated and then every 24-48 hours until decannulation. Splenic volume and the
      index of hepatic size were calculated by using published formulas. RESULTS:
      Splenic volume increased in all seven patients from 8.3 cm3 +/- 1.7 to 16.4 cm3
      +/- 4.4 (P < or = .001). Hepatic size did not change markedly. CONCLUSION:
      Hemolysis, leukopenia, and platelet activation occur during ECMO. Rapid splenic
      enlargement may be secondary to sequestration of red cells, platelets, and other
      hematologic elements that have been damaged in the ECMO circuit. Since the liver
      does not also increase in size, the splenic enlargement is unlikely to be the
      result of passive congestion.

PMID- 8284391
TI  - Vesicoureteral reflux: an accurate predictor of acute pyelonephritis in childhood
      urinary tract infection?
AB  - PURPOSE: To determine the association between vesicoureteral reflux (VUR) and the
      presence of acute pyelonephritis in children with urinary tract infections.
      MATERIALS AND METHODS: The authors studied 150 consecutive patients less than 5
      years of age with their first proved urinary tract infection. All patients
      underwent renal cortical scintigraphy (with technetium-99m dimercaptosuccinic
      acid or Tc-99m gluconate) and voiding cystourethrography (VCUG) to identify the
      presence of cortical defects and VUR, respectively. RESULTS: Of 300 kidneys, 88
      (29.3%) had a cortical defect at scintigraphy. Fifty-four of the 88 patients
      (61%) did not have VUR demonstrated at VCUG. Conversely, 72 of the 300 kidneys
      (24%) had VUR; of these, 38 (53%) had no cortical defect. The sensitivity of VCUG
      in helping predict a defect was 38.6%, and the specificity was 82.1%. CONCLUSION:
      VUR (as shown by VCUG) and renal cortical scintigraphic defects frequently occur
      independently of each other. Renal cortical scintigraphy may be a more accurate
      predictor of patients at risk for scarring.

PMID- 8284392
TI  - Focal liver lesions: characterization with nonenhanced and dynamic contrast
      material-enhanced MR imaging.
AB  - PURPOSE: To evaluate prospectively the diagnostic accuracy of non-enhanced and
      gadolinium-enhanced magnetic resonance (MR) imaging in characterization of
      hepatic lesions. MATERIALS AND METHODS: Fifty-five patients with benign and 52
      patients with malignant focal liver lesions underwent examination at 1.5 T that
      comprised nonenhanced and dynamic contrast material-enhanced images. Four
      experienced radiologists independently read the different sets of images without
      and with knowledge of clinical history. RESULTS: Receiver operating
      characteristic analysis showed that dynamic contrast-enhanced MR imaging added
      information to nonenhanced MR studies and thereby improved distinction between
      benign and malignant lesions (P < .05). Knowledge of clinical data further
      improved lesion characterization with nonenhanced and combined nonenhanced and
      contrast-enhanced MR imaging (P < .05). CONCLUSION: Dynamic contrast-enhanced MR
      imaging is a useful adjunct for characterization of hepatic lesions. Knowledge of
      clinical history still has a decisive effect on interpretation of MR images of
      the liver.

PMID- 8284393
TI  - Abdominal MR imaging: evaluation of a fast spin-echo sequence.
AB  - PURPOSE: To compare contrast of abdominal tissue on magnetic resonance (MR)
      images obtained with T2-weighted conventional spin-echo (SE) and fast spin-echo
      (FSE) sequences. MATERIALS AND METHODS: Forty-eight patients (26 men and 22
      women, aged 24-77 years) with known or suspected liver disease underwent FSE and
      SE MR imaging at 1.5 T. Signal intensity (SI) and ratios of signal-to-noise
      (S/N), signal difference-to-noise (SD/N), and SI were calculated for the spleen,
      pancreas, kidney, muscle, fat, and malignant liver lesions compared with liver.
      RESULTS: Significant differences were found between SD/N on FSE and SE images of
      all tissues, with FSE images providing lower SD/N for all tissues except fat.
      Malignant liver lesions (n = 69) showed lower SI ratios on the FSE compared with
      the SE images. Differences in mean SI ratios between malignant liver lesions and
      hemangiomas or cysts (n = 41) were significant on the FSE images (P = .01) but
      not on the SE images (P = .27). CONCLUSION: Compared with conventional T2
      weighted SE images, small but significant differences in tissue-to-liver contrast
      were obtained for some tissues, including malignant liver lesions, on FSE images.

PMID- 8284394
TI  - Hepatic abscesses: MR imaging findings.
AB  - PURPOSE: To determine magnetic resonance (MR) imaging features that characterize
      hepatic abscesses. MATERIALS AND METHODS: Clinical records and MR studies of 18
      patients with proved hepatic abscesses were evaluated. The abscesses were
      pyogenic in 15 patients, fungal in two patients, and amebic in one patient.
      RESULTS: A total of 122 lesions were identified. Most were round (n = 114) with
      sharp borders (n = 99), hypointense on T1-weighted images (n = 73), and very
      hyperintense on T2-weighted images (n = 88). After injection of gadopentetate
      dimeglumine in 43 lesions, all 43 enhanced with sharp margins and 37 showed rim
      enhancement. All abscesses followed up diminished in size (50 of 50), and
      perilesional edema resolved before the central cavity did. CONCLUSION: MR imaging
      findings seen in hepatic abscesses include high signal intensity on T2-weighted
      images (72%) and perilesional edema (43 of 122 [35%]). Rim enhancement (86%) and
      increased conspicuity (35 of 43 [81%]) were found after injection of
      gadopentetate dimeglumine.

PMID- 8284395
TI  - Pancreatic sparing of focal fatty infiltration.
AB  - PURPOSE: To describe typical findings of focal fatty sparing of the pancreas.
      MATERIALS AND METHODS: Computed tomography, ultrasonography, and/or magnetic
      resonance imaging were performed in seven patients. RESULTS: In these patients,
      the area of sparing of fatty change was within the head or uncinate process of
      the pancreas. CONCLUSION: Differentiating pancreatic fatty sparing from true
      neoplasm by means of cross-sectional imaging obviates the need for invasive
      diagnostic studies.

PMID- 8284396
TI  - Hypoechogenic embryologic ventral aspect of the head and uncinate process of the
      pancreas: in vitro correlation of US with histopathologic findings.
AB  - PURPOSE: To evaluate the hypothesis that hypoechogenicity of the embryologic
      ventral aspect of the head of the pancreas is due to diminished fat content.
      MATERIALS AND METHODS: Ultrasound and histopathologic findings in 13 pancreatic
      autopsy specimens were compared, and the prevalence of areas of hyperattenuation
      of the embryologic ventral aspect of the head of the pancreas at computed
      tomography (CT) was studied. RESULTS: In vitro examination of pancreatic autopsy
      specimens showed this variant in seven (54%) of the 13 specimens, and
      histopathologic correlation confirmed that there is diminished fat content
      corresponding to the hypoechoic portion of the head of the pancreas. This
      difference in attenuation was visible on 21 (22%) of 96 CT scans. There was a
      statistically significant (P < .05, r = .212) increase in the prevalence of this
      finding with increasing age. CONCLUSION: Hypoechogenicity of the embryologic
      ventral aspect of the head of the pancreas is due to diminished fat content. This
      difference in attenuation is also commonly seen on CT scans.

PMID- 8284397
TI  - Colitis: use of CT findings in differential diagnosis.
AB  - PURPOSE: To determine whether colitides can be differentiated based on computed
      tomographic (CT) features. MATERIALS AND METHODS: The CT scans of 117 patients
      with documented colitis and colon wall thickening were reviewed. Features
      evaluated included mural thickness and homogeneity, distribution of bowel
      involvement, and associated mesenteric and small bowel disease. RESULTS: The mean
      colon wall thickness in Crohn colitis (11.0 mm +/- 5.1) was significantly greater
      than in ulcerative colitis (7.8 mm +/- 1.9) (P < .002). Submucosal fat
      deposition, not observed in the acute colitides, was present significantly more
      often in ulcerative (61%) than in Crohn colitis (8%) (P = .0001). Exclusive
      involvement of the right colon and small bowel was most frequent with Crohn and
      infectious colitis. Abscess was associated almost exclusively with Crohn colitis
      (35%) but was seen in one patient with radiation colitis. CONCLUSION: Although
      many CT findings in patients with colitis are nonspecific, some features are
      helpful in suggesting a specific diagnosis.

PMID- 8284398
TI  - Crohn disease: early recognition and progress of aphthous lesions.
AB  - PURPOSE: To clarify the radiographic appearance of the initial change an
      dprogression in Crohn disease. MATERIALS AND METHODS: Between 1984 and 1992, nine
      patients (seven men and two women, aged 16-34 years; mean, 20 years) with Crohn
      disease, who had evidence of only aphthous erosions or ulcers at the initial
      examination, underwent repeated radiography for up to 7 years 11 months (median,
      4 years). RESULTS: In all patients, the stomach, duodenum, small intestine, and
      colorectum were involved, and the esophagus was affected in three patients.
      Subsequently, four of the nine patients had lesions that progressed from aphthous
      lesions to overt Crohn disease, including ileitis in two patients, colitis in
      one, and ileocolitis in one. Time intervals between the first visit and the
      progression varied from 9 months to 3 years 6 months. In all eight patients who
      underwent nutritional treatment, regression of the lesions was recognized, but
      three of the lesions progressed during interruption of the nutritional diet.
      CONCLUSION: Crohn disease may initially appear as diffuse aphthous lesions in the
      gastrointestinal mucosa.

PMID- 8284399
TI  - Posterior cruciate ligament injury: MR imaging diagnosis and patterns of injury.
AB  - PURPOSE: To illustrate the variety of posterior cruciate ligament (PCL) injuries
      and assess the type and frequency of associated knee injuries. MATERIALS AND
      METHODS: In a retrospective review of 1,950 magnetic resonance (MR) examinations
      of the knee, 47 patients with MR imaging findings of PCL injury were identified.
      In 24 patients, the findings on MR images were correlated with athroscopic
      findings (n = 14) or findings at physical examination (n = 10). Patterns of
      associated injuries were described and tabulated. RESULTS: Twenty-one patients
      (45%) had complete PCL tears; 22 patients (47%), partial tears; and four patients
      (9%), bone avulsion. Associated injuries were seen in 34 patients (72%). Patterns
      of injuries differed from those seen in anterior cruciate ligament injury and
      correlated with the mechanism of trauma. CONCLUSION: MR imaging proved accurate
      in assessment of the PCL in patients with clinical correlation and demonstrated
      patterns of associated injury that may affect management strategy.

PMID- 8284400
TI  - Carpal tunnel syndrome: evaluation of median nerve circulation with dynamic
      contrast-enhanced MR imaging.
AB  - PURPOSE: To identify mechanism(s) responsible for carpal tunnel syndrome (CTS).
      MATERIALS AND METHODS: At dynamic gadolinium-enhanced magnetic resonance (MR)
      imaging, the enhancement pattern of the sagittal section of the median nerve in
      10 wrists of nine patients with CTS (two men and seven women, aged 43-60 years
      [mean, 52 years 10 months]) was studied while each wrist was in a neutral,
      flexed, and/or extended position. Five asymptomatic volunteers (four men and one
      woman, aged 23-54 years [mean, 31 years 5 months]) also underwent MR imaging to
      establish the normal enhancement patterns. RESULTS: Two distinctly abnormal
      patterns of median-nerve enhancement were revealed: marked or no enhancement.
      Marked enhancement was attributed to nerve edema, and the lack of enhancement was
      attributed to ischemia. Marked enhancement changed to no enhancement changed to
      no enhancement when the wrists were in a flexed or extended position. This change
      was associated with an aggravation of the symptoms of CTS. CONCLUSIONS: CTS may
      result from a circulatory disturbance rather than from deformation or compression
      of the nerve.

PMID- 8284401
TI  - Chondroblastoma: classic and confusing appearance at MR imaging.
AB  - PURPOSE: To define the characteristics of chondroblastoma at magnetic resonance
      (MR) imaging and the combination of findings that are diagnostic for
      chondroblastoma. MATERIALS AND METHODS: From January 1987 through December 1992,
      22 patients with histologically confirmed chondroblastoma and prior MR imaging
      examinations were seen. Patients included 16 men and six women, aged 10-58 years
      (median, 17 years). Retrospective analysis of findings at MR imaging, plain
      radiography, computed tomography, and bone scanning was performed. RESULTS: Low
      to intermediate heterogeneous signal intensity, lobular internal architecture,
      and fine lobular margins were well defined with high-resolution T2-weighted
      (repetition time > or = 1,500 msec, echo time > or = 70 msec) MR imaging.
      Adjacent bone-marrow and soft-tissue edema and periosteal reactions were more
      dramatically demonstrated on MR images than on radiographs. Bone marrow edema was
      prominent in all but five cases. Obvious periosteal reaction and adjacent soft
      tissue edema were visible in 17 cases. CONCLUSION: Knowledge of the MR imaging
      findings of chondroblastoma will allow accurate diagnosis and help avoid
      confusion with infection and aggressive neoplasms.

PMID- 8284402
TI  - Abdominal diffusion mapping with use of a whole-body echo-planar system.
AB  - PURPOSE: To measure apparent diffusion coefficients (ADCs) of water in liver,
      spleen, kidney, and muscle. MATERIALS AND METHODS: Ten volunteers (seven women
      and three men, aged 19-31 years [mean, 24 years]) and nine patients (five women
      and four men, aged 49-70 years [mean, 62 years]) (liver cyst, n = 3; liver
      hemangioma, n = 3; liver cirrhosis, n = 2; hepatocellular carcinoma, n = 1; and
      liver metastasis, n = 1) underwent magnetic resonance (MR) imaging. A stimulated
      echo acquisition mode (STEAM)-type excitation and echo-planar imaging (EPI)
      readout was used in a 1.5-T echo-planar MR imaging system. RESULTS: ADCs measured
      in volunteers were liver, 1.39 x 10(-3) mm2/sec +/- 0.16; spleen, 0.95 x 10(-3)
      mm2/sec +/- 0.15; muscle, 1.99 x 10(-3) mm2/sec +/- 0.16; and kidney, 3.54 x 10(
      3) mm2/sec +/- 0.47 (mean +/- standard deviation). Distinctive ADC values were
      found in organs with abnormalities. ADCs in patients with hepatic disease
      included liver cysts, 3.9-5.3; liver hemangiomas, 2.0-2.8; liver metastases from
      an islet cell tumor, 1.2; hepatocellular carcinoma, 1.7; and liver cirrhosis, 0.9
      1.2 x 10(-3) mm2/sec. CONCLUSION: In vivo diffusion measurements of abdominal
      organs obtained with MR imaging may prove helpful in the identification and
      classification of abdominal disease.

PMID- 8284403
TI  - Isolated clustered microcalcifications: diagnostic value of mammography--series
      of 400 cases with surgical verification.
AB  - PURPOSE: To determine the diagnostic value of mammographic criteria in cases of
      isolated clustered microcalcifications. MATERIALS AND METHODS: Four hundred
      mammographic studies of isolated clustered microcalcifications for which surgical
      verification was available were reviewed. A descriptive statistical study was
      performed to evaluate the distribution of each criterion relative to
      histopathologic results, followed by a multivariate study to determine
      statistically significant criteria. Seven breast specialists gave a consensus
      opinion on the need for surgery. RESULTS: There were 302 benign lesions and 98
      cancers. The most useful criteria were vermicular form, linear/branching shape,
      and irregular size of microcalcification. The number of biopsies recommended with
      use of these three criteria was 177 instead of the 172 recommended by the
      experts. CONCLUSION: Use of these three preoperative criteria permits correct
      diagnosis of most such malignancies (90% in our series vs 67% diagnosed by the
      experts).

PMID- 8284404
TI  - Suspicious breast lesions: MR imaging with radiologic-pathologic correlation.
AB  - PURPOSE: To study the architecture and enhancement characteristics of breast
      lesions with magnetic resonance imaging. MATERIALS AND METHODS: Forty-one
      patients with mammographic and/or palpable lesions were imaged. T1-weighted, fat
      saturated T2-weighted fast spin-echo, and gadolinium-enhanced and -unenhanced fat
      saturated spoiled gradient-echo images were obtained. All patients underwent
      excisional biopsy or cyst aspiration. RESULTS: Fifteen of 16 carcinomas were
      identified and exhibited at least partially irregular borders. T2-weighted signal
      intensity and contrast enhancement varied. Rim enhancement was seen in five
      lesions. Nine of 10 fibroadenomas were visualized and showed well-defined
      borders. T2-weighted signal intensity and contrast enhancement varied and
      correlated with histologic features. Internal septations were seen in five
      lesions. Time-intensity curves showed no statistically significant difference
      between fibroadenomas and cancers. CONCLUSION: There is an overlap in the signal
      intensity characteristics and enhancement profiles of benign and malignant
      lesions. However, border characteristics, internal architecture, enhancement
      characteristics, and the presence of multiple tiny associated cysts may be
      important clues to lesion identification.

PMID- 8284405
TI  - Apocrine carcinoma: clinical and mammographic features.
AB  - PURPOSE: To describe the mammographic features of apocrine carcinoma and assess
      the patterns of calcifications associated with these lesions. MATERIALS AND
      METHODS: Clinical and mammographic features from 17 patients with apocrine
      carcinoma were retrospectively reviewed. Special attention was paid to the
      presence of mixed form, diffusely scattered microcalcifications on mammograms.
      RESULTS: Patients were referred for clinical (n = 10), mammographic (n = 2), or
      both clinical and mammographic (n = 5) abnormalities. Findings at clinical
      examination included a palpable breast mass (n = 12), multiple breast masses (n =
      1), and bloody nipple discharge (n = 2); two patients had normal findings.
      Fourteen patients had opacities at mammography. These opacities were associated
      with microcalcifications in 10 cases. Three patients had microcalcifications
      without opacities; one of those three patients exhibited a mixed form of
      diffusely scattered calcifications. CONCLUSION: Clinical and mammographic
      features of apocrine carcinoma do not differ from those of invasive ductal
      carcinoma.

PMID- 8284406
TI  - Pulmonary embolism: comparison of MR images with radionuclide and angiographic
      studies.
AB  - PURPOSE: To assess the accuracy and potential of magnetic resonance (MR) imaging
      in evaluation of patients in whom pulmonary embolism is suspected. MATERIALS AND
      METHODS: Blinded, prospective interpretations of multiphasic, cardiac-gated spin
      echo MR images were compared with retrospective chart review in 86 patients in
      whom pulmonary embolism was suspected. In 64 patients, the presence or absence of
      pulmonary emboli was established with x-ray angiography (n = 34) or ventilation
      perfusion (V-P) scans and concurrent clinical impression (n = 30). RESULTS: In
      the subgroup with angiographic proof, MR imaging had a sensitivity of 90%,
      specificity of 77%, positive predictive value of 86%, and negative predictive
      value of 83%. In 21 patients with intermediate probability of pulmonary embolism
      on V-P scans and angiograms, MR images enabled diagnosis of pulmonary embolism in
      12 of 12 patients (sensitivity, 100%) and absence of pulmonary embolism in seven
      of nine patients (specificity, 78%). CONCLUSION: MR imaging reliably depicts
      large and medium-size pulmonary emboli, regardless of infiltrates or effusion;
      hence, it may clarify findings on V-P scans that show intermediate probability of
      pulmonary embolism or are at variance with the clinical impression.

PMID- 8284407
TI  - Pulmonary embolism in patients with intermediate probability lung scans:
      diagnosis with Doppler venous US and D-dimer measurement.
AB  - PURPOSE: To test the usefulness of lower limb Doppler venous compression
      ultrasound (US) and serum D-dimer measurements in diagnosis of pulmonary embolism
      in patients in whom ventilation-perfusion (V-P) scans indicate intermediate
      probability of pulmonary embolism. MATERIALS AND METHODS: V-P scanning, pulmonary
      angiography, US, and D-dimer measurements were performed in 36 patients without
      known deep venous thrombosis but with intermediate probability of having a
      pulmonary embolism. RESULTS: Pulmonary angiography demonstrated pulmonary
      embolism in 15 (41%) of 36 patients. US demonstrated deep venous thrombosis in
      only two patients, both with pulmonary embolism. Sensitivity of US was only 13%,
      but specificity was 100%. Five (14%) of the 36 patients had normal (< 220
      micrograms/L) D-dimer levels; none of the five had pulmonary embolism.
      Sensitivity and specificity of D-dimer values were 100% and 16%, respectively,
      with a negative predictive value of 100%. CONCLUSION: Combined D-dimer
      measurement and US were helpful in correctly diagnosing pulmonary embolism in
      only seven (20%) of 36 patients. Pulmonary angiography is still required to
      diagnose pulmonary embolism in the majority of patients.

PMID- 8284408
TI  - Pulmonary nodules and the CT halo sign.
AB  - PURPOSE: To determine whether the "halo sign" at computed tomography (CT) could
      be used to differentiate hemorrhagic from nonhemorrhagic pulmonary nodules.
      MATERIALS AND METHODS: CT scans of 12 patients with hemorrhagic pulmonary nodules
      and of a control group of 10 patients with nonhemorrhagic pulmonary nodules were
      randomized and reviewed by two chest radiologists. Nodules were considered
      hemorrhagic if a surrounding halo of ground-glass attenuation was present.
      RESULTS: Nodules were correctly identified as either hemorrhagic or
      nonhemorrhagic by both observers in 19 of the 22 cases (86%). Eight of the 12
      patients with hemorrhagic nodules had an infectious process including invasive
      aspergillosis, candidiasis, cytomegalovirus, herpes simplex virus, or
      coccidioidomycosis. Four of 12 patients with hemorrhagic nodules had a
      noninfectious cause including Wegener granulomatosis, metastatic angiosarcoma,
      and Kaposi sarcoma. CONCLUSION: Most hemorrhagic pulmonary nodules have a
      characteristic CT appearance consisting of a central area of soft-tissue
      attenuation with a surrounding halo of ground-glass attenuation that allows
      distinction from nonhemorrhagic nodules.

PMID- 8284409
TI  - Thoracic CT images: effect of lossy image compression on diagnostic accuracy.
AB  - PURPOSE: To evaluate the effects of lossy image (noninvertible) compression on
      diagnostic accuracy of thoracic computed tomographic images. MATERIALS AND
      METHODS: Sixty images from patients with mediastinal adenopathy and pulmonary
      nodules were compressed to six different levels with tree-structured vector
      quantization. Three radiologists then used the original and compressed images for
      diagnosis. Unlike many previous receiver operating characteristic-based studies
      that used confidence rankings and binary detection tasks, this study examined the
      sensitivity and predictive value positive scores from nonbinary detection tasks.
      RESULTS: At the 5% significance level, there was no statistically significant
      difference in diagnostic accuracy of image assessment at compression rates of up
      to 9:1. CONCLUSION: The techniques presented for evaluation of image quality do
      not depend on the specific compression algorithm and provide a useful approach to
      evaluation of the benefits of any lossy image processing technique.

PMID- 8284410
TI  - Scanning slit chest radiography: a practical and efficient scatter control
      design.
AB  - PURPOSE: To design a chest radiography unit that eliminates scatter. MATERIALS
      AND METHODS: A scanning slit radiography unit that also incorporates a
      conventional grid was designed. The scanning slit geometry defined a 10-mm-wide
      beam at the image receptor. RESULTS: With a typical heavy-duty radiographic tube,
      the proposed system was capable of delivering an entrance skin exposure of up to
      32 microC/kg for a 1-second scan. Monte Carlo simulations indicated that the
      scatter-to-primary ratio (S/P) imaged with the scanning slit system alone was
      0.125 for a 35 x 43-cm, 23-cm-thick Lucite phantom imaged at 140 kVp. When the
      system was coupled with 4:1, 8:1, and 12:1 grids, S/P decreased to 0.063, 0.055,
      and 0.054, respectively. CONCLUSION: A scanning slit system coupled with a
      conventional grid is a practical and highly efficient method of controlling
      scatter and will result in minimal soft-tissue and bone measurement errors in
      dual-energy chest radiography.

PMID- 8284411
TI  - Treatment of autonomous thyroid nodules with percutaneous ethanol injection: 4
      year experience.
AB  - PURPOSE: To evaluate the long-term efficacy of treatment of autonomous thyroid
      nodules with percutaneous ethanol injection under ultrasound guidance. MATERIALS
      AND METHODS: Treatment was performed in 101 patients. The mean ratio of injected
      ethanol volume to nodule volume was approximately 1.5; ethanol was usually
      administered in four to eight sessions. RESULTS: Complete cure was achieved in 59
      patients. Partial cure was achieved in 34 patients. Eight patients had remission
      of thyrotoxicosis but persistence of thyroid-stimulating hormone level
      suppression and radionuclide uptake only in the nodule. The extent of the
      response was inversely proportional to the nodule volume. Marked nodule shrinkage
      was observed in all groups. No recurrences were observed. Transient vocal cord
      paresis occurred in four patients, with full recovery in all cases. CONCLUSION:
      This method compares favorably with both surgery and radioiodine treatment,
      especially when the very low prevalence of posttreatment hypothyroidism is
      considered.

PMID- 8284412
TI  - Nasolacrimal duct obstruction treated nonsurgically with use of plastic stents.
AB  - PURPOSE: To evaluate the clinical utility of plastic stents in treatment of
      complete obstruction of the nasolacrimal duct. MATERIALS AND METHODS: Nineteen
      plastic stents were successfully placed under fluoroscopic guidance in 16
      consecutive patients with epiphora due to complete obstruction of the
      nasolacrimal duct. After balloon dilation of the obstructed area, the stents were
      placed in the lacrimal system with the head portion lying in the dilated lacrimal
      sac and the body in the nasolacrimal duct and projecting into the inferior meatus
      of the nasal cavity. RESULTS: Complete resolution of epiphora was accomplished in
      15 (79%) of 19 eyes and partial resolution in the remaining four (21%) eyes.
      CONCLUSION: These preliminary results with use of plastic nasolacrimal stents are
      encouraging.

PMID- 8284413
TI  - Cranial tissues: appearance at gadolinium-enhanced and nonenhanced MR imaging
      with magnetization transfer contrast.
AB  - PURPOSE: To determine the relative contrast of normal cranial tissues at
      magnetization transfer (MT) spin-echo magnetic resonance (MR) imaging. MATERIALS
      AND METHODS: MR imaging at 1.5 T was performed with conventional spin-echo
      techniques without and with off-resonance MT saturation pulses. The signal
      intensities of normal cranial tissues were measured in 10 healthy volunteers on
      spin-density- and T2-weighted images and in 10 patients on T1- weighted images
      obtained before and after administration of gadopentetate dimeglumine. RESULTS:
      MT saturation produced a significant (P < .01) reduction in signal from all
      tissues except cerebrospinal fluid and fat. Several gray matter structures had
      higher signal intensity than white matter on T1-weighted MT images. After
      administration of gadopentetate dimeglumine, imaging with the MT sequence
      increased visualization of normally enhancing structures. CONCLUSION: MT
      saturation pulses produce new patterns of tissue contrast that differ
      substantially from those seen on conventional spin-echo images.

PMID- 8284414
TI  - Cerebral infarction: effects of dose and magnetization transfer saturation at
      gadolinium-enhanced MR imaging.
AB  - PURPOSE: To determine contrast enhancement after cerebral infarction at T1
      weighted magnetic resonance (MR) imaging with delayed, gadolinium-enhanced, and
      magnetization transfer (MT) techniques. MATERIALS AND METHODS: Ten patients aged
      40-81 years with recent infarctions (< 7 days) were prospectively studied at MR
      imaging. Gadoteridol (0.1 mmol/kg [standard dose] and an additional 0.2 mmol/kg
      [high dose]) was administered before imaging with and without MT saturation and
      after a 15-minute delay. Two neuroradiologists ranked enhancement conspicuity.
      RESULTS: interobserver concordance was excellent (kappa = .86). Pairwise
      comparisons revealed high-dose MT images were ranked highest, followed by high
      dose delayed non-MT images (P < .01). Standard-dose MT images and initial high
      dose non-MT images were ranked intermediately but were not distinguishable from
      each other (P > .05). Initial and delayed standard-dose MT images were ranked
      lowest (P < .01) and were not distinguishable from each other. CONCLUSION: MT
      saturation and high-dose gadoteridol individually and synergistically improve the
      depiction of contrast enhancement.

PMID- 8284415
TI  - Improved contrast of enhancing brain lesions on postgadolinium, T1-weighted spin
      echo images with use of magnetization transfer.
AB  - PURPOSE: To prove that the contrast of enhancing brain lesions on post-gadolinium
      T1-weighted spin-echo (SE) images can be statistically significantly improved
      with magnetization-transfer (MT) indirect saturation. MATERIALS AND METHODS: The
      contrast-to-noise ratios (C/Ns) of 201 enhancing brain lesions in 110 patients
      were compared on conventional and MT T1-weighted SE images obtained at 1.5 T
      after injection of 0.05-0.10 mmol/kg gadopentetate dimeglumine or gadodiamide.
      RESULTS: The MT T1-weighted SE images showed a 37% reduction in signal intensity
      of background white matter and thereby provided a 108% improvement in the C/N of
      enhancing brain lesions over the conventional T1-weighted SE images (P < .001).
      CONCLUSION: The C/Ns obtained with single-dose gadolinium and the MT T1-weighted
      SE technique were twice those obtained with the conventional technique and are at
      least equivalent to reported values obtained with triple-dose gadolinium and
      conventional T1-weighted SE images.

PMID- 8284416
TI  - Shunt flow measurement and evaluation of valve oscillation with a spin-echo phase
      contrast MR sequence.
AB  - PURPOSE: To present a spin-echo phase-contrast (SEPC) magnetic resonance pulse
      sequence designed to measure the very slow flow in ventricular shunt tubing.
      MATERIALS AND METHODS: A flow phantom constructed of shunt tubing and
      incorporating no valve or a high-, medium-, or low-pressure valve was connected
      to a flow pump. Flow rates were 0.05-1.00 mL/min (72-1,440 mL/d). Flow
      measurement was performed with the thin-section SEPC sequence. RESULTS: The flow
      rates measured with SEPC imaging correlated closely with the pump flow rate for
      the entire physiologic spectrum of shunt flow rates. This was true for all
      valves, resulting in overall R2s of .974 at 4 cm/sec and .980 at 2 cm/sec. Shunt
      flow was pulsatile with valves in place. There was a linear relationship between
      flow rate and the frequency of valve opening and closing. CONCLUSION: The SEPC
      technique is an accurate and noninvasive method of measuring shunt flow.

PMID- 8284417
TI  - Metallic artifacts on MR images of the postoperative spine: reduction with fast
      spin-echo techniques.
AB  - PURPOSE: To determine whether the relative insensitivity of T2-weighted fast spin
      echo (FSE) techniques to magnetic susceptibility can be exploited to reduce
      metallic artifacts on images of the postoperative spine and, thus, improve the
      interpretation of the postoperative study. MATERIALS AND METHODS: Three
      neuroradiologists retrospectively evaluated sagittal T2-weighted conventional
      spin-echo and FSE images obtained in 15 patients with metallic artifacts from
      various sources including drill particles from anterior cervical diskectomy,
      posterior fixation wires, fixation rods or plates, and an inferior vena cava
      filter. The amount of artifact present and whether these artifacts affected image
      interpretation were evaluated. RESULTS: Among the 45 paired evaluations, the
      artifact was judged to be less apparent with FSE sequences in 39. In eight of 45
      evaluations (18%), the interpretation of the area of interest was possible only
      on the FSE images. CONCLUSION: FSE imaging, especially when performed with
      shorter echo spacing, increases the amount of T2-weighted information in the
      presence of metallic artifact because it decreases magnetic susceptibility
      effects.

PMID- 8284418
TI  - How to write a successful abstract.

PMID- 8284419
TI  - US of breast biopsy specimens.
AB  - From January 1990 through December 1992, 1,585 preoperative wire localization
      procedures of occult breast lesions were performed at the authors' institution.
      Of these, 739 (47%) were masses, and ultrasound (US) guidance was performed to
      localize 30 lesions. In five of the 30 lesions, no mass was seen at radiography
      of the specimen, but US of the specimen helped confirm complete excision.

PMID- 8284420
TI  - Presacral abscesses: percutaneous transperineal drainage with use of bone
      landmarks and fluoroscopic guidance.
AB  - Presacral abscesses developed in two men (aged 59 and 76 years) after
      abdominoperineal resection. Computed tomography was performed to demonstrate the
      distance from the abscess to the perineum and the distance of the abscess
      anterior to the sacrum. Then, lateral and anteroposterior fluoroscopy was
      performed to guide transperineal drainage catheter placement. No complications
      occurred, and clinical outcome was successful in both cases.

PMID- 8284421
TI  - Deep venous thrombosis: value of self-augmentation US evaluation.
AB  - In 10 healthy volunteers (three men and seven women, aged 24-35 years [mean, 27
      years]) and 28 patients (11 men and 17 women, aged 38-74 years [mean, 60 years])
      with symptoms for deep venous thrombosis (DVT), self-augmentation ultrasound (US)
      scanning was performed. The technique resulted in diagnostically useful venous
      flow augmentation in the femoropopliteal veins in all 10 (100%) limbs of
      volunteers, in 25 of 27 (93%) limbs of patients without DVT, and in two of seven
      (29%) limbs of patients with DVT. Of the patients in whom self-augmentation
      failed, two could not perform the maneuver and five had scans positive for DVT.

PMID- 8284422
TI  - Coronary arteries: new design for three-dimensional arterial phantoms.
AB  - Few three-dimensional (3D) anthropomorphic phantoms are available for testing 3D
      reconstruction and quantitation of vessels. The authors built a new realistic
      model of arteries with use of stereolithography, a computer-aided design and
      computer-aided manufacturing technique. Each phantom is composed of the physical
      object and its digital "twin." The entire coronary artery tree and complex
      stenoses were manufactured with a precision below 0.1 mm.

PMID- 8284423
TI  - After all, wood would float, wouldn't it?

PMID- 8284424
TI  - US appearance of ruptured silicone breast implants.

PMID- 8284425
TI  - Abdominal-gastrointestinal radiology.

PMID- 8284426
TI  - Genitourinary radiology.

PMID- 8284427
TI  - Cardiovascular/interventional radiology.

PMID- 8284428
TI  - Musculoskeletal radiology.

PMID- 8284429
TI  - Ultrasonography.

PMID- 8284430
TI  - Head and neck radiology.

PMID- 8284431
TI  - Nuclear medicine.

PMID- 8284432
TI  - Pediatric radiology.

PMID- 8284433
TI  - Evaluation of left ventricular function by impedance cardiography: a review.
AB  - There are a number of different methods by which the impedance waveform can at
      least partly predict ventricular function. Of these methods, the measurement of
      systolic time intervals has been best validated. However, much work still needs
      to be done on a wide variety of ICU and non-ICU patients to validate a stable and
      predictable relationship between PEP/VET and EF. Further work may also validate
      the other indices discussed above, but less confidence can be expressed as to
      their eventual clinical use at present. All of the work to date has examined the
      relationship between impedance and LV function. Although the impedance tracing is
      known to largely reflect LV ejection and aortic root flow, there may be some
      contribution from right ventricular function. To further evaluate this
      contribution, work using first-pass radionuclear techniques to selectively look
      at right ventricular EF will need to be done.

PMID- 8284434
TI  - Quantitative hemodynamics by Doppler echocardiography: a noninvasive alternative
      to cardiac catheterization.
AB  - Doppler echocardiography has greatly enhanced the information provided by two
      dimensional echocardiography. By providing information concerning pressure
      gradients, intracardiac pressures, volumetric flow, and diastolic filling of the
      heart, most hemodynamic information that in the past could be obtained only from
      cardiac catheterization can now be provided accurately and noninvasively by
      Doppler echocardiography. Future developments in instrument technology and
      understanding of the various Doppler velocity curves should further aid in the
      ability to obtain a complete, noninvasive hemodynamic assessment of the patient
      with cardiac disease.

PMID- 8284435
TI  - The neurobiology of narcolepsy-cataplexy.

PMID- 8284436
TI  - In vitro studies of visual cortical development and plasticity.

PMID- 8284437
TI  - Spatial and temporal aspects of spinal cord and brainstem activation in the
      formalin pain model.

PMID- 8284438
TI  - [The privileged background of Drosophila, as a material for developmental biology
      studies].

PMID- 8284439
TI  - [Genes that control embryogenesis of caenorhabditis elegans].

PMID- 8284440
TI  - [Genetic control of early zebrafish development].

PMID- 8284441
TI  - [Important genes during early development of Xenopus laevis].

PMID- 8284442
TI  - [The molecular mechanism of dorsoventral polarity formation in Drosophila
      embryos].

PMID- 8284443
TI  - [Molecular and developmental mechanisms of neuronal diversities in D.
      melanogaster].

PMID- 8284444
TI  - [Neuron network formation in vertebrates].

PMID- 8284445
TI  - [Signal transduction and morphogenesis].

PMID- 8284446
TI  - [Adhesion molecules in animal development].

PMID- 8284447
TI  - [Regulation of yeast morphogenesis].

PMID- 8284448
TI  - New perspectives of combined radiation and chemotherapy in oncology.

PMID- 8284449
TI  - Mechanisms of radiation resistance.

PMID- 8284450
TI  - Combined radiation and chemotherapy in head and neck cancer.

PMID- 8284451
TI  - Combined radiation and chemotherapy in the management of cervical cancer.

PMID- 8284452
TI  - Combined radiation and chemotherapy in non oat-cell lung cancer.

PMID- 8284453
TI  - Combined radiation and chemotherapy in esophageal cancer.

PMID- 8284454
TI  - Combined radiation and chemotherapy in anal carcinoma.

PMID- 8284455
TI  - Combined radiation and chemotherapy in rectal cancer.

PMID- 8284456
TI  - Concomitant radiation and chemotherapy with mitomycin-C in advanced head and neck
      cancer.

PMID- 8284457
TI  - Combined radiation and chemotherapy in the treatment of gynecologic malignancies:
      preliminary results.

PMID- 8284458
TI  - Combined radiation and chemotherapy in lung cancer: preliminary results.

PMID- 8284459
TI  - Combined radiation and chemotherapy in anal carcinoma: preliminary results.

PMID- 8284460
TI  - Combined radiation and chemotherapy of resectable stage II-III carcinoma of mid
      lower rectum: preliminary results.

PMID- 8284461
TI  - Combined radiation and chemotherapy in locally advanced rectal cancer:
      preliminary results.

PMID- 8284462
TI  - T-lymphocyte subsets in cancer patients undergoing radiotherapy and their
      recovery after thymostimulin treatment. A cooperative study.

PMID- 8284463
TI  - [Experimental study of dislocations of the scapulohumeral joint].
AB  - One may produce easily an experimental dislocation (anterior or erecta) of the
      scapulohumeral joint. The authors discuss, the experimental model then they
      describe the anatomical lesion produced through the experimental dislocation of
      32 shoulders and the correlation observed after RMI assessment of 24 recurrent
      dislocations. The tear of the inferior glenohumeral ligament is constant, in 20
      per cent of the cases the tear lies on the anterior aspect of the glenoid, in the
      other cases the tear was found on its humeral side. Whatever the situation of the
      tear of the inferior glenohumeral ligament, the lesion of the labrum was
      constant. The erecta dislocation was produced with the same movement but with a
      particular tear of the glenohumeral ligament: the tear was longitudinal. The
      experimental dislocation needs, in 7 or 8 cases, a desinsertion of the deep
      aspect of the rotator cuff. The Hill Sachs lesion occurs when the humerus falls
      along the chest wall after the dislocation. In 50 per cent of the patients, MRI
      shows modifications of the cuff which are compatible with our results. Hills
      Sachs lesions appear to be constant after MRI examination.

PMID- 8284464
TI  - [AIDS and orthopedic surgery].

PMID- 8284465
TI  - [Periprosthetic ossifications of the hip: role of the duration of postoperative
      indomethacin therapy in the prevention of ossifications and role of screwed
      acetabulum in the occurrence of ossification].
AB  - After showing, as many others did, in an article published in 1987, that
      indomethacin administered immediately after surgery and for about 3 weeks at a
      dose of 75 mg/day effectively protected THA against heterotopic ossification, the
      authors have searched whether treatment duration could be reduced, and to
      investigate the existence of risk factors other than those classically known.
      They studied the prevalence of heterotopic ossification in two groups of THA with
      known risks of ossification, one with one-week prophylaxis, the other with two
      week prophylaxis using Indomethacin. The results obtained were compared with a
      third group of THA performed during the same period, which presented no known
      risk of ossification and were not treated with indomethacin, and with the THAs of
      the initial study, where indomethacin had been administered for 3 weeks.
      Occurrence of heterotopic ossification was equally prevented by an 8-day course
      and by a longer one. No etiological, radiological or pathological risk factor
      other than those described in 1987 were fund (with all due caution given to hips
      re-operated on that had not ossified the first time): in contrast, the type or
      acetabular cup appears to have some influence on the occurrence of HO: uncemented
      prosthesis clearly favours ossification.

PMID- 8284466
TI  - [Gamma nail in the treatment of closed trochanteric fractures. Results and
      indications apropos of 121 cases].
AB  - The Gamma Nail, developed at the Centre for traumatology and orthopaedics of
      Strasbourg, is the latest advance in the treatment of trochanteric fractures,
      based on the intra-medullary principle and on the closed procedure. It was
      inspired both by the Y nail of Kuntscher and by the interloking nail. This is the
      study of the results of a first series of 121 cases treated between 1988 and 1990
      and followed until consolidation. The mean age was 75 years, mostly patients in
      poor general condition, unstable fracture types were predominant. The
      preoperative reduction was anatomic in 72 per cent and the quality of
      osteosynthesis was good in 66 per cent, acceptable in 27 per cent; 83.4 per cent
      of the patients resumed full weight bearing during the first week. Only one case
      of deep infection occurred, treated by Gentamicyn beeds without removal of the
      nail. The mortality rate was 12.3 per cent at three months. We note 7 malunions
      in varus > 10 degrees, 3 in valgus > 10 degrees, 2 in external rotation > 10
      degrees and 1 internal rotation > 10 degrees. In six cases, there was a cut out
      of the femoral head by the screw (in two cases the screws were too short, in four
      cases they were in a bad position). The same criticism against all surgical
      methods of treatment of trochanteric fractures can be done against the Gamma
      Nail. Nevertheless, it keeps the advantages of a closed procedure and, in
      comparison to the Ender nail, the absence of knee pain and the systematic weight
      bearing whatever the fracture type.

PMID- 8284467
TI  - [Surgery of the foot in equinus deformity in hemiplegic adults].
AB  - The authors report the results of surgical treatment of the equinus deformity of
      the foot in adult hemiplegia performed on 23 patients with a long term follow-up
      for 20 of them. Surgical treatment required two phases. Firstly, a spasticity
      correction by scopiform neurotomy of the posterior tibial nerve: this operation
      had to be done 14 times because of the importance of the spasticity. Secondly, a
      phase of truly orthopaedic surgery which involved successively, a treatment of
      the equinus deformity by lengthening of the Achilles tendon, a restoration of the
      dorsal flexion by anterior muscle transfer and some complementary operations on
      the forefoot. An astragalo-scaphoid arthrodesis was associated in the 13 most
      recent cases. Results were subjectively judged very good or good for 17 patients.
      Objectively, walking appliances have been reduced, gait was more secure and a
      greater autonomy has been reached. However, the goals of this surgery are limited
      as it has no incidence on central interferent lesions and neuropsychological
      troubles resulting from brain damage. The quality of the result is, in other
      respects, conditional upon the gait pattern of the whole limb, particularly upon
      the importance of the flexion of the knee during the step cycle.

PMID- 8284468
TI  - [Intraarticular fractures of the calcaneus: pathological description.
      Contribution of x-ray computed tomography].
AB  - Computed tomography (CT) is of cardinal importance in the study of displaced
      intra-articular fractures of the calcaneus, as with this imaging technique the
      primary fracture line of Palmer can be followed and its various locations
      visualised. If the three-stage classification system of these fractures as
      vertical, horizontal or mixed fractures, based on their radiological appearance,
      is adopted, a correlation can be established between the location of Palmer's
      line and these three anatomical types. The fundamental fracture line is medial in
      the vertical types, lateral in the horizontal types and is located in the centre
      of the posterior facet in the mixed types. It can be seen that the fundamental
      fracture line separates a laterally detached fragment which is always tilted,
      giving a vertical slope to the surface of the posterior facet which it supports
      and thus giving a vertical image. This fragment is itself separated from a
      medially detached fragment which is tilted horizontally and produces a horizontal
      image on the lateral view. The CT sections must be examined for the presence of a
      secondary sagittal line completely isolating the horizontally tilted fragment.
      The importance of the location of the fundamental fracture line, which is on the
      borderline between tilting and horizontalisation, suggests that pronation
      supination of the foot is a factor in the causal mechanism of these fractures. A
      clear understanding of the three-dimensional position of the fragments and of
      their displacement, essentially defined by the location of the fracture line, is
      a prequisite before attempting surgical reduction of calcaneal fractures.

PMID- 8284469
TI  - [HIV virus and orthopedic surgery].
AB  - The risks of HIV viral transmission by blood transfusion or by bone
      transplantation during planned surgical orthopaedic procedures has been studied
      from French epidemiological data on the subject. The authors outline methods
      which may be used to reduce these risks: planned auto-transfusion of blood,
      serological assessment of a donor and quarantine of allograft material. Finally,
      the authors have examined the risks of contamination of the surgical team during
      an operation.

PMID- 8284470
TI  - [Apophysitis of the iliac crest. A little known cause of low back pain and pelvic
      pain in children].
AB  - The authors describe an iliac osteochondrosis in 98 teenagers aged of 12 to 17
      years, responsible for anterior, medial or posterior pains of pelvis and the
      lumbar zone, squaring with the period of ossification of the iliac crest. The
      spontaneous pain was revived by pressing a precise zone of the iliac crest. These
      pains have the usual characteristics of the pains of ossification of apophysis.
      The identification of the characteristics allows to avoid any further
      investigation which will have to be realised in case of doubt or modification of
      the evoluting symtomatology. It is to recognize this cause of pain so as not to
      attribute it to a regional morphological anomaly that may lead to excessive
      surgical indications. The evolution was constantly favourable after a few weeks
      delay. Only a momentary and adapted restriction of sporting activities is
      justified.

PMID- 8284471
TI  - [Epidermoid carcinoma arising in femoral osteitis. A case].
AB  - The authors report a case of malignant degeneration arising from a fistula in a
      patient with chronic osteomyelitis of the femur. This rare complication (0.2 per
      cent-1.6 per cent) most frequently involves the lower limb. A review of the
      literature reveals that it is associated with long-standing osteomyelitis (30
      years), is most frequently a squamous cell carcinoma or rarely a sarcoma, and is
      principally treated by surgical amputation. The frequency of metastatic spread is
      low (30 per cent). Malignant degeneration appears to be a local phenomenon, and
      if diagnosed early, has a rather favorable outcome following complete excision.

PMID- 8284472
TI  - [Acrometastasis of the hand presenting as a whitlow. General review apropos of a
      case].
AB  - Acrometastases are rarely diagnosed. We present a new case. A literature review
      provides the opportunity to summarise the frequency, the clinical forms, the
      diagnoses, and proposed treatments. A biopsy of each chronic lesion in the hand,
      even without anamnesis seems to be indicated.

PMID- 8284473
TI  - [Primary rhabdomyosarcoma of bone. Apropos of a spinal localization].
AB  - The authors describe one case of rhabdomyosarcoma of the second thoracic
      vertebra. The primitive osseous nature is discussed through an analysis of the
      case and a review of the literature.

PMID- 8284474
TI  - [The national public health network: a new system of intervention epidemiology].

PMID- 8284475
TI  - [Conditions and limitations of healthy carrier screening for the mutation
      responsible for cystic fibrosis].
AB  - Cystic Fibrosis is an autosomal, recessive and lethal disease which affects one
      newborn in 2500 in most of European countries. The gene has been cloned and most
      of the deleterious mutations have been identified. This has led to a complete
      change in attitude to cystic fibrosis from a public health standpoint. Prenatal
      diagnosis is now available for couples of carriers (each unaffected parent
      carrying a deleterious mutation) with a 1/4 risk of having an affected newborn.
      Prenatal diagnosis can be performed through three different but complementary
      procedures with an overall reliability of 98%. As these couples at risk are
      identified by a first affected newborn, prenatal diagnosis may only prevent
      further ones. General screening of carriers would be valuable from a public
      health standpoint, for it could prevent the first affected newborn and would
      decrease very much the incidence of the disease. Such carrier screening is
      theoretically feasible through the direct analysis of identified deleterious
      mutations of the gene in the DNA of both parents, before any pregnancy. However
      there are major obstacles to general screening. On the one hand unidentified
      mutations are still numerous, except in certain populations, so screening is not
      perfect. On the other hand, the larger the number of tested mutations (and thus
      the better the efficiency of screening), the more expensive the procedure. New
      and cheaper screening technologies are therefore required but as yet unavailable.
      Moreover, due to the genetic variability within human populations, reliable
      screening can only be performed within certain homogeneous ethnic sub
      populations. This limitation may raise ethical and public health questions.

PMID- 8284476
TI  - [Past and present asthma mortality: towards a shift in the secular trend?].
AB  - In recent years disconcerting observations have been published concerning changes
      in mortality from asthma in France and other countries. These conclusions are
      difficult to assess due to uncertainty regarding the underlying asthma mortality
      trends. We have attempted to address this question by constituting a statistical
      series of asthma deaths from 1925 to 1989. The 1925 to 1989 mortality trend is
      clearly decreasing. This decrease follows the same rhythm as the general
      mortality decline, since the proportion of asthma in total deaths remained
      between 3 to 4/1000. Three periods are emphasized: from 1925 to 1965 where the
      decreasing trend is interrupted by an important crisis in mortality, from 1965 to
      1980 where the decrease is regular, and the last period since 1980 with an
      important crisis in 1985 and 1986; crisis applying to all genders and ages. The
      latest trend is uncertain. Careful epidemiologic surveillance will decide between
      a change in the secular trend or a transitory crisis and thus determine the
      cause(s). An effect due to the reinclusion by ICD 9 of a fluctuating component in
      asthma mortality cannot be excluded.

PMID- 8284477
TI  - Cancer mortality by urbanization and altitude in a limited area in Northeastern
      Italy.
AB  - The geographical patterns of cancer mortality have been studied in Friuli-Venezia
      Giulia Region (1.2 million inhabitants), the North-eastern part of Italy, with
      respect to certain characteristics (i.e., rural, mixed, urban) and the altitude
      of the commune where the deceased subjects lived permanently at the time of
      death. In males, significantly increased mortality rates in rural versus urban
      communes (after allowance for altitude) were found for cancer of the oral cavity
      and pharynx, oesophagus and stomach. Conversely, significantly decreased
      mortality rates emerged for cancer of the colo-rectum, liver, lung, bladder,
      kidney and Hodgkin's disease. In females, significantly increased mortality rates
      in rural as compared to urban communes were observed for stomach cancer while
      significantly decreased mortality rates emerged for cancer of the colo-rectum,
      gallbladder, lung, breast, ovary, bladder and brain. With respect to altitude,
      residence above 200 meters retained a significant association in males, after
      allowance for the degree of urbanization of the commune of residence, for cancer
      of the oral cavity and pharynx, stomach and larynx (positive) and cancer of the
      colorectum and brain (negative). Women in locations above 200 meters seemed
      significantly at risk for stomach cancer, but protected from cancer of the colo
      rectum and kidney. These results may provide a useful summary guide for further
      aetiological investigations into the risk factors associated with the diseases
      and give practical indications for local strategies of cancer control.

PMID- 8284478
TI  - [Prevalence of sleep and wakefulness disorders in high school students at the
      Academy of Lyon].
AB  - We studied sleep and wakefulness disorders in high schools of the Lyon district.
      Data were collected by auto-questionnaire from a very large sample (11,923 boys
      and 13,870 girls) of high school students, between 15 and 20 years of age.
      Thirteen per cent of boys and 17% of girls complained of poor sleep, and the most
      frequent trouble was difficulty in falling asleep. The difference between the
      length of the sleep during school time and holidays was greater than 3 hours for
      24% of the students. About 10% of students who reported habitual difficulties in
      falling asleep used drugs (at least once a week) which facilitate sleep. The use
      of sleeping pills by the family correlated with that by the subject: 5% of boys
      belonging to families using sleeping pills are themselves users compared to 1% in
      the whole sample. Students using hypnotic drugs frequently had daytime naps (14%
      versus 3%); their morning wakefulness was poorer and their afternoon wakefulness
      better than students who did not.

PMID- 8284479
TI  - [Survival rate of elderly patients with senile dementia according to type of
      institutional care. Comparison between "long stay hospitals" and structures of
      the type "cantou"].
AB  - The proliferation of new forms of so-called "non-medical" care for the elderly
      suffering from dementia raises the problem of the subsequent impact of this
      development on the quality of the care given. One way of approaching this
      question is to examine survival of the persons admitted to this form of care. A
      comparison was made of the survival of elderly persons admitted to an innovative
      "non-medical" form of care (units known as "cantou") with that of elderly
      patients in long-stay hospital care. A retrospective analysis was carried out of
      the survival of 707 elderly persons with dementia admitted into both types of
      care between the 1st of May 1978 and the 15th of September 1988. After
      controlling for age, sex and date of admission no significant difference in
      survival was found between the two forms of care. This supports the notion that
      the quality of medical care in the "cantou" is not fundamentally different from
      that provided by long-stay hospitals.

PMID- 8284480
TI  - [Cost effectiveness evaluation of breast cancer therapy. Comparative analysis
      1975-1985 in a cancer prevention center].
AB  - We describe a retrospective and comparative assessment of the medical care of
      breast cancer among women in a French comprehensive cancer center, the Centre
      Claudius Regaud. There was no significant difference for the clinical results
      between two cohorts of women, treated in 1975 and 1985 respectively, for
      equivalent stages of disease. The overall increase in survival resulted mainly
      from early diagnosis. Locoregional treatment cost and conservative treatment
      cost, from official Social Security costs, did not increase between the two
      periods. However, a high risk of metastasis risk during the first treatment, or
      recurrence during the follow-up, resulted in differences in cost-effectiveness
      between 1975 and 1985. Although these results must be interpreted with caution,
      this analysis raises strategic questions about the suitability of some medical
      practices, particularly in the care of evolutive neoplasm.

PMID- 8284481
TI  - [Computer analysis of audiograms in epidemiologic surveillance of cohorts exposed
      to excessive noise].
AB  - We have developed a method for the assessment of auditive loss using a sample of
      1794 Bekesy audiograms recorded in young military students. A rectangular digital
      filter was used to smooth rough audiogram signals so as to detect pathological
      patterns such as scotoms and recruitments. Three factors were extracted from
      principal component analysis. They were correlated with the usual auditory
      indices and explained 70% of the total observed variance. The first factor is a
      general indicator of deafness, while the second and third describe the shapes of
      the hearing threshold level (asymmetry and convexity). This method can be used
      for rapid identification of suspect audiograms and is thus of value for
      epidemiological surveillance of populations exposed to impulsive noise.

PMID- 8284482
TI  - [Development of a simple and reliable method for estimating malaria morbidity
      according to the modified Muench model].
AB  - To evaluate malaria control measures one needs to document morbidity trends over
      time. Malaria morbidity incidence rates (MMIR) can be estimated from multi-round
      surveys that use specially designed questionnaires, but they are cumbersome and
      very expensive. Parasitological incidence rates (PIR), in contrast, can be
      estimated from malariometric indices, which are simple to collect, but are
      difficult to interpret in terms of morbidity. We present an extension of Muench's
      mathematical model which overcomes this drawback. Between June 1990 and May 1991,
      data were collected in Nyanza-lac, South Burundi, in two parallel studies of
      children under 6 years old. A fortnightly morbidity recall survey documented MMIR
      by age. Thick blood films were collected bimonthly to calculate PIR according to
      Muench's model. The proportion of high parasitaemia (PHP) was defined as the
      number of slides with 100% of the examined microscopic fields positive for at
      least one asexual form of Plasmodium falciparum over the total number of slides
      examined. To test the hypothesis that parasitological data can provide an
      accurate approximation of malaria morbidity, age specific PIR were multiplied by
      the corresponding PHP to obtain the incidence rate of high parasitaemia (HPIR).
      Close agreement was found between MMIR and HPIR (regression coefficient = 1.15;
      r2 = 98%). Thus, this method offers a simple, accurate and cost-efficient
      alternative for questionnaire-based morbidity surveys.

PMID- 8284483
TI  - [Mortality and morbidity of drug addiction increases in France].

PMID- 8284484
TI  - [Family policies in the European community in 1991].

PMID- 8284485
TI  - [The 40th anniversary of the WHO regional bureau for Europe].

PMID- 8284486
TI  - Secretory component and IgA expression by epithelial cells in sow mammary gland
      and mammary secretions.
AB  - Secretory component (SC) and IgA expression of epithelial cells were studied in
      the mammary tissue and mammary secretions of sows. In mammary tissue, SC was not
      detected until day 105 of gestation. From the time of delivery (day 115) to the
      time of established lactation, the proportion of epithelial cells containing SC
      rose from 20 per cent to nearly 100 per cent. There was no IgA in alveolar
      epithelial cells until day 105 of gestation; on day 115, IgA positive epithelial
      cells were present in 10 per cent of the alveoli, which increased to 80 per cent
      during lactation. Epithelial cells represented more than 20 per cent of the total
      cells in colostrum, and predominated over leucocytes in milk. In colostrum, these
      epithelial cells (9 to 15 microns) showed weakly positive membrane, SC, contained
      cytoplasmic SC and had a limited capacity for in vitro proliferation. Ten per
      cent of epithelial cells contained intracytroplasmic IgA. In milk, the epithelial
      cells were larger (15 to 40 microns) with a higher expression of both membrane
      and intracytoplasmic SC; 66 per cent of these cells expressed intracytoplasmic
      IgA. These data showed that the capacity of mammary epithelium to process IgA to
      secretory IgA was complete at the end of mammary gland organisation, and
      established that the epithelial cells of milk contribute to the transfer of IgA
      to neonates.

PMID- 8284487
TI  - Prenatal diagnosis of bovine citrullinaemia.
AB  - Holstein/Friesian embryos, progeny of citrullinaemia heterozygotes, were
      transferred to recipient cows. The citrullinaemia genotype of the fetus/calf was
      established, at birth, by estimation of citrulline concentration in plasma or by
      analyses of argininosuccinate synthetase exon 5 sequences in DNA from blood
      leucocytes. Between 115 and 125 days of gestation amniotic fluid was collected
      transabdominally from nine recipient cows. The mean citrulline concentration in
      amniotic fluid from fetuses unaffected with citrullinaemia was 28 microM, SD 9
      and range 15 to 38 microM. Citrulline concentration was 107 and 130 microM in
      amniotic fluid from two fetuses homozygous for the citrullinaemia mutation. Only
      the normal bovine citrullinaemia sequence was detected in cells cultured from
      amniotic fluid taken from two homozygous normal and two heterozygous fetuses.
      Both normal and mutant sequences were found in cells cultured from amniotic fluid
      collected from three of five heterozygous fetuses. Only the mutant sequence was
      found in cells cultured from the two citrullinaemia affected fetuses. MHC class
      II DRB3 haplotyping revealed that in four instances cultured cells were from the
      surrogate mother, not the fetus, these included samples from two heterozygotes in
      which only the normal sequence was detected in amniotic fluid.

PMID- 8284488
TI  - Serum enzyme activity evaluated in budgerigars (Melopsittacus undulatus)
      inflicted with muscle injury.
AB  - Aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase
      (CK) and lactate dehydrogenase (LDH) concentrations were measured in 73
      budgerigars. In spite of increases in the serum concentration of AST and ALT the
      loss of enzyme activity from the injection site occurred at about the same rate
      for all four enzymes tested. The rate constants, calculated in birds administered
      muscle extract via the intravenous or the intramuscular route of injection,
      disclosed that in subjects treated intramuscularly the serum enzyme elevation was
      dependent on the elimination half-life of the enzyme and partly on the rate at
      which the particular enzyme was absorbed into the bloodstream. Moreover, serum
      enzyme elevations correlated inversely with total clearance. To determine the
      aetiology of blood enzyme elevation in budgerigars, for diagnostic purposes, the
      absorption rate, total clearance and elimination half-life of each of these four
      enzymes are deemed valuable components.

PMID- 8284490
TI  - Seroepidemiological study of Taenia saginata cysticercosis in Swaziland.
AB  - A cross-sectional study of Taenia saginata cysticercosis in Swaziland using a
      serodiagnostic ELISA for parasite antigen is described. The seroprevalence and
      the levels of parasite antigen were compared in the sera of cattle from different
      geographical localities, and from areas of high or low population density. Cattle
      from the Lowveldt region, which has a hot and dry climate relative to the other
      areas investigated, exhibited significantly higher serum antigen levels.
      Seroprevalence was also higher in the Lowveldt but this difference was not found
      to be significant. Within the Lowveldt, antigen levels were found to be slightly
      elevated in cattle from more highly populated areas. It is suggested that either
      human behaviour and/or practices in animal husbandry, or increased susceptibility
      of cattle to reinfection at certain times of the year, may enhance transmission
      in the Lowveldt since climatic conditions in this region are not conducive to
      transmission.

PMID- 8284489
TI  - Protective immunity following immunisation of pigs with aerosol of Actinobacillus
      pleuropneumoniae serotype 2.
AB  - To introduce antigen to the respiratory mucosa, killed Actinobacillus
      pleuropneumoniae with quil A as adjuvant was administered to pigs as an aerosol.
      Immunisation by this aerosol induced a marked IgA response in the bronchoalveolar
      and nasal fluids, and in the serum. Following challenge with live bacteria two
      weeks after the last exposure to the aerosol, the immunised pigs were protected
      from the severe pleuropneumonia which developed in non-immunised pigs. The
      immunised pigs had lower antibody titres in the mucosal fluids and serum after
      exposure to the challenge. The immune response after experimental infection of
      non-immunised animals was a weak IgA antibody response in the bronchoalveolar and
      nasal fluids, whereas the systemic immune response after challenge included both
      IgA and IgG antibodies.

PMID- 8284491
TI  - Maturation of cellular defence in the respiratory tract of young calves.
AB  - The maturation of respiratory tract defence was investigated in a longitudinal
      study of calves during the first 100 days of life. From day 7, the proportions of
      the cell types identified in bronchoalveolar lavage (BAL) fluid were similar to
      those found in adults, with a predominance of alveolar macrophages over
      polymorphonuclear neutrophils (PMNs) and lymphocytes. Functionally, bactericidal
      activity of BAL cells was defective and for the first 21 days they supported
      intracellular bacterial growth. At 24 hours of life, the movement of peripheral
      blood neutrophils to a chemotactic source was poor, but this increased rapidly
      during the first week of life. Like BAL cells, peripheral blood PMNs supported
      intracellular bacterial growth for the first two weeks of life. These studies
      suggest that cellular defence mechanisms may be compromised during the first week
      of life.

PMID- 8284492
TI  - Alteration of cellular immune responses by nutrition and weaning in calves.
AB  - The effects of two levels of nutrition (400 g and 1000 g air dry matter milk
      substitute powder per day) and three ages of weaning (five, nine and 13 weeks) on
      cellular immune responses were determined in 32 calves. The lower level of
      nutrition was found to increase skin sensitivity responses to keyhole limpet
      haemocyanin (KLH) and decrease lymphocyte blastogenesis test (LBT) responses to
      ConA and pokewood mitogen (P < 0.05). Weaning at five weeks old resulted in
      increased KLH skin responses at nine weeks old compared with unweaned calves and
      decreased LBT responses to ConA and phyto-haemagglutinin at 10 weeks old compared
      with calves weaned at nine weeks old (P < 0.05). Weaning at five weeks old also
      increased peripheral blood concentrations of BoCD2+ and BoCD8+ lymphocytes (P <
      0.05). The results show that the choice of husbandry conditions alters cellular
      immune responses in young calves and suggest that early weaning effects are
      essentially nutritional.

PMID- 8284493
TI  - Feed intake affects metabolic clearance rate of progesterone in sheep.
AB  - To study the inverse relationship between feed level and concentrations of
      peripheral plasma progesterone, 36 ovariectomised ewes were fed rations at levels
      calculated to maintain liveweight (M). On the seventh day, the ewes were given an
      intravenous infusion of progesterone and the metabolic clearance rate (MCR) was
      calculated. The ewes were then randomly allotted to receive either 1/2M, M or 2M
      rations for seven days at which time the infusion and blood sampling schedules
      were repeated. The mean (SE) MCR of infused progesterone in ovariectomised ewes
      fed either 1/2M, M or 2M rations for seven days was 7.1 (0.59), 9.9 (1.64 and
      13.0 (1.19) litre h-1 kg-1 of liveweight, respectively. Differences in MCR of
      progesterone between ewes fed 1/2M and 2M rations were significant (P < 0.05).
      The inverse relationship between level of feed intake and plasma progesterone
      concentration was attributed to differences in clearance rate of progesterone
      rather than to changes in the entry rate of the hormone into the blood.

PMID- 8284494
TI  - Liver blood flow and metabolic clearance rate of progesterone in sheep.
AB  - To study the effects of feeding on concentrations of peripheral plasma
      progesterone, ovariectomised ewes, given exogenous progesterone, were fed 750 g
      of chopped lucerne hay at either 09.00 (group A, n = 5) or at 15.00 (group B, n =
      5) or were fed ad libitum regularly through the experimental period (group C, n =
      5). Peripheral blood samples were taken from each ewe at 09.00, 11.00, 15.00,
      17.00 and 23.00. In ewes of groups A and B, mean plasma progesterone
      concentrations declined significantly (P < 0.05) after feeding. Mean progesterone
      concentrations of group C ewes remained low and were significantly different (P <
      0.05) from the pre-feeding values of group A and B ewes. These results showed
      that the metabolic clearance rate of progesterone changed with the act of
      feeding. In a second experiment, portal, hepatic and mesenteric vein cannulae
      were placed in ovariectomised ewes (n = 17). They were then fed a ration
      calculated to maintain liveweight for seven days (M ration). The ewes were then
      infused with progesterone into a jugular vein and with p-amino hippuric acid into
      a mesenteric vein. Ewes were then allotted to receive either half M or twice M
      rations for seven days after which the infusions and blood sampling procedures
      were repeated. The mean rate of blood flow in the portal vein was directly
      related to the level of feed offered when ewes received either 1/2M, M or 2M
      rations. The liver and gut region removed a mean of 96 per cent of the
      progesterone entering these tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284495
TI  - Purification and quantitative measurement of bovine serum amyloid-A.
AB  - Bovine serum amyloid-A (b-SAA) was purified from a pool of acute phase serum
      using hydrophobic interaction chromatography and gel filtration. Serum was
      applied at a low salt concentration to a phenyl-sepharose column and SAA was
      eluted with a gradient of 0 to 6 M guanidine-HCl. Fractions containing SAA were
      pooled, concentrated and further purified by gel filtration on Superose-12. The
      concentration of SAA in bovine serum was quantified by an indirect ELISA using
      rabbit anti-human SAA and horseradish peroxidase conjugated donkey anti-rabbit
      IgG. Dilutions of an acute phase bovine serum sample were used as working
      standards. The SAA concentration of this standard was determined by comparison
      with purified b-SAA on SDS-polyacrylamide gel electrophoresis followed by
      densitometry at 590 nm. The assay detection limit was 3 micrograms ml-1; the
      intra-assay coefficient of variation was 4 per cent and interassay coefficients
      of variation were 5.5 per cent and 7.2 per cent at 66 and 178 micrograms ml-1
      SAA, respectively. In calves experimentally infected with Pasteurella haemolytica
      type A1 the ELISA was able to detect a 10-fold increase of SAA within 24 hours of
      inoculation.

PMID- 8284496
TI  - Evaluation of canine small intestinal permeability using the lactulose/rhamnose
      urinary excretion test.
AB  - The use of the lactulose and rhamnose urinary excretion test was evaluated in
      dogs with gastrointestinal disease. Lactulose and rhamnose urinary excretion was
      measured in three groups of dogs: clinically healthy dogs and dogs with
      gastrointestinal disease with and without coexistent panhypoproteinaemia. A
      significant increase in both the percentage of lactulose:percentage of rhamnose
      urinary excretion ratio and the percentage of lactulose excretion was
      demonstrated in dogs with hypoproteinaemia when compared to the other two groups.
      The results suggest that the lactulose/rhamnose urinary excretion test may prove
      a useful adjunct to currently available tests for assessing small intestinal
      function, but lacks sensitivity in detecting small intestinal mucosal damage in
      the absence of villus atrophy.

PMID- 8284497
TI  - Morphometric study of the recurrent laryngeal nerve in young 'normal' horses.
AB  - Quantitative measurements were made on cross-sectional preparations of the distal
      part of the recurrent laryngeal nerve (RLN) from nine young mixed-breed horses to
      establish reference values for the total number of myelinated fibres, mean fibre
      diameter and percentage of thickest fibres (over 9.5 microns) and to delineate
      diameter distribution curves. The total number of myelinated fibres, mean fibre
      diameter and percentage of thickest fibres for the left RLN were significantly
      lower than those of the right RLN (P < 0.005). The distribution of fibres was
      unimodal. The fibre diameter ranged from 1 micron to 17 microns. Approximately,
      95 per cent of fibres had a diameter larger than 5 microns.

PMID- 8284498
TI  - Biochemical and haematological changes following prolonged halothane anaesthesia
      in horses.
AB  - Six healthy horses were anaesthetised with halothane (1.2 times the horse minimal
      alveolar concentration) in oxygen for more than 12 hours. Serum bilirubin,
      aspartate aminotransferase, alkaline phosphatase and L-iditol dehydrogenase
      values were significantly (P < 0.05) increased for up to nine days after
      anaesthesia. These changes suggest an anaesthesia related liver dysfunction.
      Creatine kinase increased to an average of more than 1400 IU litre-1 24 hours
      after anaesthesia and this change is indicative of muscle cell disruption. Renal
      associated biochemical results, (that is serum creatinine and inorganic phosphate
      concentrations) were significantly increased transiently and are indicative of
      reduced renal function during and immediately after anaesthesia. Plasma
      concentrations of eicosanoids (6-keto-PGF1a, PGF2a, PGE and thromboxane)
      following anaesthesia were not different from preanaesthetic values. The
      magnitude of liver and muscle cell related increases in serum enzyme activities
      resulting from prolonged halothane anaesthesia was in excess of that previously
      reported for anaesthesia of shorter duration.

PMID- 8284499
TI  - Abnormalities of collagen fibrils in a rabbit with a connective tissue defect
      similar to Ehlers-Danlos syndrome.
AB  - A morphometric ultrastructural study was performed to confirm the presence of an
      abnormality of the collagen fibrils in a rabbit with a connective tissue defect
      similar to Ehlers-Danlos syndrome. Median fibril diameter and perimeter were not
      altered but their ranges were significantly increased. As indicated by the median
      fibril 'form factor', fibrils were significantly more irregular in shape; the
      range of irregularity in shape was also increased. Fibril periodicity was
      unchanged. The results are discussed in relation to collagen fibril structure and
      fibril abnormalities in similar diseases in man and other animals.

PMID- 8284500
TI  - Lymphocyte subsets in the mammary gland of sows.
AB  - The presence and localisation of lymphocyte subsets together with class II
      bearing cells in the mammary gland of sows, were studied at different periods of
      the reproductive cycle by immunohistochemistry and compared with blood. All cell
      types involved in the immune response were present in the mammary gland at the
      different stages of gestation and lactation and nearer the alveolar epithelium as
      gestation proceeded: T lymphocytes, including CD4+ and CD8+, B lymphocytes and
      class II bearing cells (epithelial cells and macrophages). The results indicated
      an early accumulation of T lymphocytes, specifically T helper cells, during
      pregnancy; the specific increase of IgA lymphocytes occurring after this phase
      could suggest a role for these T cells in the induction of IgA response. The
      local accumulation of immune cells sustains the view that the mammary gland is
      able to mount a true local immune response and the increase in CD8+ cells near
      the epithelium suggests a role in local immune defence.

PMID- 8284501
TI  - Isolation of Corynebacterium pseudotuberculosis from the cervical canal of
      clinically normal sows.
AB  - Two isolates from the cervical canal of clinically normal sows were
      indistinguishable from Corynebacterium pseudotuberculosis in their biochemical
      properties and genetic homology by DNA-DNA hybridisation. Furthermore, three
      sheep inoculated with one of the isolates developed typical lesions of caseous
      lymphadenitis and gave antibody responses specifically to C pseudotuberculosis.

PMID- 8284502
TI  - Plasmid encoded beta-lactamases resistant to inhibition by clavulanic acid
      produced by calf faecal coliforms.
AB  - Two new plasmid encoded beta-lactamase enzymes produced by a strain of
      Escherichia coli and a strain of Citrobacter freundii isolated from calf faeces
      have been characterised. Both enzymes were similar to TEM-1 in terms of substrate
      and inhibition profiles and physical properties but differed from TEM-1 in being
      far less susceptible to the beta-lactamase inhibitors clavulanic acid or
      tazobactam. In each case transfer of the plasmid E coli K12 rendered it
      clinically resistant to the combination of amoxycillin and clavulanic acid. The
      beta-lactamase from the E coli had an iso-electric point (pI) of 5.4 and was
      encoded on a plasmid of 95 Kbp which also mediated resistance to tetracycline,
      sulphonamides, apramycin, streptomycin and gentamicin. The beta-lactamase from
      the C freundii had a pI of 5.2 and was encoded on a 75 Kbp plasmid which also
      mediated resistance to trimethoprim, chloramphenicol, apramycin, gentamicin and
      tobramycin.

PMID- 8284503
TI  - Serum and mucosal antibody responses against Mycoplasma hyopneumoniae following
      intraperitoneal vaccination and challenge of pigs with M hyopneumoniae.
AB  - Pigs were immunised intraperitoneally when six weeks old and again at about 10
      weeks old with killed Mycoplasma hyopneumoniae antigen prepared in an oil
      adjuvant. The pigs were challenged with live M hyopneumoniae (Beaufort strain) at
      between 11 and 15 weeks old. Antigen specific antibody levels for both IgG and
      IgA classes in serum and respiratory tract secretion were monitored over time. In
      serum anti-M hyopneumoniae antibody was detected shortly after the second
      intraperitoneal vaccination and was largely IgG. In respiratory tract secretion
      the response was observed after challenge, and was primarily IgA. Anti-M
      hyopneumoniae antibody-containing cells and their immunoglobulin class
      specificity were monitored in lung and tracheal lamina propria. In lung the
      majority of anti-M hyopneumoniae-containing cells were IgG, whereas in the
      tracheal lamina propria the majority were IgA. These results are discussed in
      terms of the use of intraperitoneal vaccination for the control of M
      hyopneumoniae infection.

PMID- 8284504
TI  - Isolation of infectious laryngotracheitis virus from proximal femora of lame
      broiler chickens.
AB  - Two herpesviruses previously isolated from seven of 19 affected joint/bone
      samples in an earlier survey of lameness in broilers were identified. They were
      characterised as infectious laryngotracheitis (ILT) virus using serum
      neutralisation, immunofluorescence, restriction enzyme analysis and polymerase
      chain reaction techniques. In experimentally infected chicks, one of the isolates
      caused mild ILT and intranuclear inclusion bodies were present in the tracheal
      epithelium after four days. It is considered unlikely that these viruses were
      involved in the pathological changes in the affected legs. The possibility that
      ILT pathogenesis and epidemiology are more complex than currently understood is
      discussed.

PMID- 8284505
TI  - Plasma cortisol concentrations in dogs given cortisone or placebo by mouth.
AB  - Fasted normal dogs (n = 8) were given fixed doses of cortisone acetate orally as
      5 mg and 25 mg tablets; plasma cortisol concentrations were determined, and Cmax,
      tmax and area under the curve of plasma cortisol concentration plotted against
      time from zero to 12 hours were compared for the two preparations. In addition,
      these variables were compared when 25 mg tablets were administered with and
      without food. No significant difference in cortisol availability was noted for
      the two preparations and feeding did not apparently affect cortisone absorption.
      The findings in two hypoadrenocorticoid dogs were similar. Plasma cortisol
      concentrations in placebo-treated dogs similarly sampled showed minor
      fluctuations and were generally within accepted reference limits for normal dogs.

PMID- 8284506
TI  - Uterine activity after ovariectomy in the camel (Camelus dromedarius): effect of
      exogenous administration of oestrogen and progesterone.
AB  - During oestrous cycles of the camel, spontaneous uterine contractions were
      correlated significantly with plasma oestradiol-17 beta concentration.
      Ovariectomy in the camel resulted in a decreased plasma concentration of
      oestradiol-17 beta (< 15 pg ml-1) and progesterone (< 0.1 ng ml-1) and caused
      complete cessation of uterine activity. Daily administration of oestradiol
      benzoate (5 mg, intramuscularly) increased the plasma concentration of oestradiol
      17 beta (> 45 pg ml-1) and increased the frequency and amplitude of uterine
      activity. Coadministration of progesterone (100 mg, intramuscularly) increased
      the plasma concentration of progesterone (> 4 ng ml-1) and increased the
      frequency but not amplitude of uterine activity. It is suggested that uterine
      activity in the camel is correlated with the circulating levels of oestradiol-17
      beta and progesterone.

PMID- 8284507
TI  - Viral antibodies in bovine fetuses in Argentina.
AB  - In order to establish the prevalence of viral infections of the bovine fetus in
      Argentina, a serological survey for antibodies against viral agents currently
      affecting cattle in this country was conducted. Antibodies against foot-and-mouth
      disease virus (FMDV), bovine herpesvirus-1 (BHV-1), bovine leukaemia virus (BLV),
      bovine rotavirus (BRV), bovine coronavirus (BCV), bovine viral diarrhoea virus
      (BVDV) and parainfluenza-3 (PI-3) were investigated in a total of 315 fetal serum
      samples. Conventional techniques were used: indirect immunofluorescence (FMDV,
      BHV-1, BVDV and BCV), radial immunodiffusion (BLV), ELISA (BRV) and
      haemagglutination inhibition (PI-3). Antibodies against BHV-1, BVDV and PI-3 were
      detected in samples from fetuses in the second and third trimester of gestation,
      with a prevalence of 1.21 per cent (two of 165), 2.03 per cent (four of 197) and
      5.08 per cent (nine of 177), respectively. Either antibodies or non-antibody
      factors able to bind to BRV and BCV antigens were detected with a prevalence of
      2.44 per cent (five of 205) and 4.54 per cent (five of 110), respectively. In
      addition, 14.68 per cent of non-specific inhibitors of PI-3 mediated
      haemagglutination were found. No seropositives against FMDV and BLV were
      detected.

PMID- 8284508
TI  - A new technique for accessing the cerebral ventricles of the horse.
AB  - A technique is described for catheterisation of the ventricular recess within the
      olfactory bulb of the horse. Twelve adult horses were used. The olfactory recess
      is in the frontal region, 42 +/- 3 mm below the skin, on the line joining the
      supraorbital foramina, and approximately 18 +/- 2 mm from the midline. The
      approach is relatively easy under normal experimental conditions.

PMID- 8284509
TI  - Dose-response relationship of atracurium besylate in the halothane-anaesthetised
      pig.
AB  - The dose response relationship for the intermediate-acting non-depolarising
      muscle relaxant, atracurium besylate in the pig was determined using evoked
      electromyography. An incremental dose technique was used in seven Large
      White/Landrace crossbred pigs anaesthetised with nitrous oxide and halothane.
      ED50 and ED95 were 510 +/- 87 micrograms kg-1 and 1150 +/- 270 micrograms kg-1,
      respectively. Although these values may represent an overestimate, they provide a
      reasonable guideline for the use of atracurium by veterinary anaesthetists.

PMID- 8284510
TI  - Comparison of serum, milk and urine as samples in an enzyme immunoassay for
      bovine leukaemia virus infection.
AB  - Serum, milk and urine specimens were taken from 15 bovine leukaemia virus (BLV)
      positive and 20 BLV-negative cattle which had been determined previously to be
      infected or not by the use of a monoclonal enzyme-linked immunosorbent assay
      (ELISA). An ELISA was performed on the samples for the detection of IgG1
      antibodies to the BLV surface glycoprotein, gp 51. The three types of samples had
      parallel optical density (OD) values apart from three urine samples which,
      although accepted as negative for anti-BLV antibodies, had numerically higher ODS
      than those of control BLV-negative animals. Therefore, detection of IgG1
      antibodies against BLV in the urine of naturally infected animals could be an
      indication for the use of urine for diagnosis of BLV infection.

PMID- 8284511
TI  - Biological characterisation of an Indian isolate of egg drop syndrome-76 virus.
AB  - An isolate of egg drop syndrome-76 virus replicated best in primary chicken
      embryo liver cells and less well in duck embryo liver cells, duck embryo
      fibroblast cells and chicken embryo kidney cells. The cytopathic effect in
      chicken embryo liver cells was marked by the presence of round and refractile
      cells and detachment of cells from the glass surface. The intranuclear
      eosinophilic inclusion bodies were observed by 24 to 48 hours after infection. No
      virus multiplication was observed in primary quail embryo fibroblast cells,
      chicken embryo fibroblast cells or mammalian cells like Vero, BHK-21 and MDBK.
      Duck embryos supported the maximum growth of the virus, with allantoic fluid
      having the highest haemagglutinin titre, followed in order by chorioallantoic
      membrane, skin and internal organs. Chicken and quail embryos did not support the
      growth of the virus.

PMID- 8284512
TI  - In vitro transcripts of turnip yellow mosaic virus encompassing a long 3'
      extension or produced from a full-length cDNA clone harbouring a 2 kb-long PCR
      amplified segment are infectious.
AB  - Two types of full-length cDNA clones have been constructed corresponding to the
      entire genome of turnip yellow mosaic virus (TYMV), from which infectious
      transcripts devoid of 5' non-viral extensions can be synthesized in vitro. The
      first type of transcript (tTYFL7) harbours 75 non-viral nucleotides at its 3'
      end, whereas the second type (tTYFL84) possesses only 2 non-viral nucleotides at
      its 3' end. The 2 kilobase-long 3' region of tTYFL84 derives from amplification
      by the polymerase chain reaction of the corresponding TYMV cDNA. Both tTYFL7 and
      tTYFL84 are infectious in rapeseed protoplasts and plants. tTYFL7 is far less
      infectious than wild-type TYMV RNA and somewhat less infectious than tTYFL84. The
      possible effects of the 3' extraviral sequences of tTYFL7 and the heterogeneity
      observed in the infectivity of other transcripts prepared as was tTYFL84 are
      discussed.

PMID- 8284513
TI  - Cucumber mosaic virus-associated RNA 5. XIII.--Opposite necrogenicities in tomato
      of variants with large 5' half insertion/deletion regions.
AB  - Two satellite RNA of cucumber mosaic virus (CMV) designated J876-CARNA-5 (for
      cucumber mosaic virus-associated RNA-5) and D27-CARNA-5 have been molecularly and
      biologically characterized. J876-CARNA-5 (387 nucleotides (nt)) and D27-CARNA-5
      (391 nt) have nearly identical 5' half insertion/deletion regions where 120 nt
      replace approximately 70 nt of D-CARNA-5 (335 nt), the first variant described
      and sequenced. J876-CARNA-5 possesses the 15-nt conserved sequence element in its
      3' half which is present in all tomato necrogenic variants and induces the same
      level of necrosis in tomatoes as the prototype necrogenic D-CARNA-5. D27-CARNA-5
      lacks the 3' half necrosis-determining element and attenuates the CMV symptoms in
      tomato. Transcripts of cloned cDNA of J876-CARNA-5 were stably propagated in
      tomato in the presence of CMV-1. Purified J876-CARNA-5 progeny, inoculated with
      CMV-1 in a quantitative bioassay, induced tomato necrosis at the same dilution
      level as the natural satellite. Several computer-generated secondary structures
      of CMV satellites were examined and the possible correlation of a defined
      secondary structural element with necrosis induction is discussed.

PMID- 8284514
TI  - The VP4 gene sequence of a haemagglutinating strain of feline rotavirus.

PMID- 8284515
TI  - Molecular cloning of single-stranded DNA purified from scrapie-infected hamster
      brain.
AB  - Homogenized normal and scrapie-infected hamster brains were subjected to
      subcellular fractionation. A single band of ssDNA corresponding to about 1.2 kb
      was purified by alkaline gel electrophoresis from the nucleic acid content of
      enriched preparations of mitochondria/tubulofilamentous particles. The ssDNA was
      synthesized into double-stranded DNA using Taq polymerase with four dNTP for
      extension. The cDNA synthesized was inserted in M13mp10, cloned and sequenced. An
      unusual palindromic six-base TACGTA repeat sequence was obtained and confirmed by
      an independent automated pathway and by cutting with a specific restriction
      enzyme. Comparison of the nucleotide sequence of the inserted DNA with the
      GenBank nucleotide database revealed no significant homology with those
      sequences. A probe prepared from the Nar 50 clone hybridized with the scrapie DNA
      band of about 1.2 kb noted above; however, no hybridization was observed with
      normal DNA, thus confirming the presence of ssDNA in scrapie. The presence of
      palindromic sequences in the scrapie genome could explain why many previous
      searches have revealed no evidence for a scrapie-specific nucleic acid.

PMID- 8284516
TI  - Transient immunosuppressive effect induced in rabbits and mice by the human
      spumaretrovirus prototype HFV (human foamy virus).
AB  - Spumaviruses (foamy viruses) constitute one of the three retroviral genera
      isolated from man. Although spumaviruses have not been clearly linked to a given
      pathology in humans and other infected species, it is well established that they
      lead in vivo to chronic infections without detectable viral expression. We
      thought it of interest to investigate certain aspects of the pathology induced in
      laboratory animals by human foamy virus (HFV). In this work, we demonstrate that
      HFV infection of rabbits and mice gives rise to a transient immunosuppressive
      effect, as evaluated in vitro by lymphocyte transformation tests. This phenomenon
      occurs shortly after viral inoculation, at around 4-5 days, and regresses within
      thirty days.

PMID- 8284517
TI  - Enzyme-linked immunosorbent assay for antibodies to ZEBRA, an Epstein-Barr trans
      activator.
AB  - Patients with AIDS and AIDS-related complex often show symptoms of Epstein-Barr
      virus (EBV) reactivation. Several EBV-encoded trans-acting factors activate the
      EBV lytic cycle, and one, called ZEBRA (BamHI Z EBV replication activator),
      controls the switch of EBV from a latent to a productive cycle. We describe here
      a simple ELISA test using a bacterially expressed ZEBRA protein as antigen.
      Utilizing this technique, we evaluated the humoral response to ZEBRA antigen in
      38 patients with nasopharyngeal carcinoma and 134 subjects with an asymptomatic
      HIV 1 infection. The control group consisted of 40 healthy adult blood donors.

PMID- 8284518
TI  - Meteorological variables and occurrence of respiratory syncytial virus in
      Uruguay.

PMID- 8284519
TI  - Apoptosis and subacute spongiform encephalopathies.

PMID- 8284520
TI  - Wheezing triggered by dorsal decubitus: pulmonary function changes.
AB  - In 23 subjects with chronic obstructive pulmonary disease (COPD) who wheezed when
      changing their position from sitting to dorsal decubitus (DD), we recorded lung
      volumes and flow volume loops in sitting (S1), DD and immediately after resuming
      sitting (S2). We found three main patterns of ventilatory changes associated with
      wheezing in DD: (1) acute obstruction (AO) in 14 subjects characterized by FEV1 >
      or = -10% and %FEV1/FVC > or = -3%; functional residual capacity or residual
      volume was increased, decreased or unchanged; (2) acute restriction (AR) in 7
      subjects characterized by absence of obstruction spirographically and FVC and/or
      FRC > -10%; (3) indeterminate response (IR) in 2 subjects. Except for 3 subjects,
      the changes recorded in DD returned to baseline in S2. Both AO and AR responses
      in DD and their rapid resolution in S2 were reproducible (11 subjects). IN
      CONCLUSION: (1) in COPD, DD may trigger wheezing; (2) the physiologic changes
      during DD wheezing are reproducible, rapidly reversible when the sitting position
      is resumed and unlike those recorded during bronchoprovocation, heterogeneous.

PMID- 8284521
TI  - Immediate allergic and nonallergic reactivity of the airways in Ascaris skin
      sensitive sheep.
AB  - Immediate airway reactivity to Ascaris suum allergen was compared with the
      responses to nonallergic airway challenge using histamine and acetylcholine in
      sheep with positive skin reactions to the allergen. In a control group of 6 sheep
      with negative skin test responses, allergen aerosol inhalation and allergen
      extract infusion only caused minor changes in mechanics of breathing as well as
      in arterial plasma histamine concentration. Nearly 40% of the animals with a
      positive skin test responded to allergen inhalation with an acute airway
      obstruction, whereas all animals bronchoconstricted after allergen infusion.
      Bronchoconstriction was associated with an increase in arterial plasma histamine
      concentrations. The difference between the two groups of skin test-positive sheep
      seems to be due to the amount of histamine liberation after allergen exposure.
      Allergen infusion caused a more severe increase of airway resistance and plasma
      histamine levels in animals responding to allergen inhalation than in animals
      responding to allergen infusion only. Similar responses were obtained in both
      groups after inhalation and infusion of histamine and acetylcholine. Since the
      slope of the responses (dEdyn/dHi.Pl.) was similar in both groups of animals we
      conclude that the sensitivity of receptors is similar in responders to allergen
      inhalation and in animals responding to allergen infusion only.

PMID- 8284522
TI  - Elevated ventilatory equivalents during exercise in patients with
      hyperventilation syndrome.
AB  - In hyperventilation syndrome (HVS), hyperventilation is often provoked by
      exercise. This study was undertaken to investigate gas exchange parameters and
      their correlation to arterial blood gas values in HVS patients during exercise.
      Ventilatory equivalents for oxygen (VE/VO2) and carbon dioxide (VE/VCO2) were
      significantly higher in HVS patients than in the controls. (VE/VO2) during light
      exercise (40-50 W) was 23.1 +/- 2.7 (n = 10) in the controls and 35.2 +/- 8.2 (n
      = 10) in the HVS group (p < 0.01). VE/VCO2 during light exercise was 30.0 +/- 3.3
      in the controls and 41.8 +/- 6.0 in the HVS group (p < 0.01). In HVS,
      significantly correlations were observed between VE/VCO2 and PaCO2, and between
      VE/VO2 and PaCO2 during both light and maximal exercise (p < 0.02). The findings
      suggest that exercise testing can be used to aid HVS diagnosis without invasive
      arterial cannulation.

PMID- 8284523
TI  - Effects of flow and resistive training on respiratory muscle endurance and
      strength.
AB  - This study was conducted to ascertain whether resistive or flow type training
      would better improve both strength and endurance in the respiratory muscles of
      healthy subjects. Subjects performed a battery of respiratory strength and
      endurance tests before and after training, which consisted of either control,
      cycling exercise (E), inspiratory loading (IL), expiratory loading (EL), or
      hyperventilation (H) training for 4 weeks. Maximal sustained ventilation
      increased after training in the E and H groups. Both IL and H improved
      inspiratory fatigue resistance. IL improved maximal inspiratory pressure. No
      significant changes were found in maximal expiratory pressure although E, EL, and
      H tended to improve. There was no statistical difference in maximal voluntary
      ventilation between groups after training, but the H group alone did increase.
      This study suggests that respiratory muscle strength and endurance can be
      improved with flow or resistive training. Flow type training improves both flow
      and resistive tests while resistive training appears to affect only strength and
      resistive type measurements.

PMID- 8284524
TI  - Percutaneous transthoracic fine-needle lung biopsy with 3 different needles. A
      retrospective study of results and complications in 224 patients.
AB  - During 1986-1990, 307 percutaneous transthoracic fine-needle biopsies (PTNB) were
      performed on 224 patients (mean age 63 years, range 27-83) with three types of
      needles (Nordenstrom, Vacu-Cut and Franzen). The overall sensitivity regarding
      malignant disease in central and peripheral pulmonary lesions was 67.0%. In 71
      patients with suspected malignancy and a negative PTNB, the examination was
      repeated and the sensitivity was increased to 79.5%. Each needle had the
      following sensitivity: Nordenstrom 67.4%, Vacu-Cut 75.7%, Franzen 75.9%. The
      overall pneumothorax frequency was 24.7%, being highest with the Nordenstrom
      needle. Hemoptysis was seen in 5 examinations. In conclusion, the Franzen and
      Vacu-Cut needles have a significantly higher sensitivity and a lower complication
      frequency compared to the Nordenstrom needle.

PMID- 8284525
TI  - Percutaneous lung biopsy with a semi-automatic, spring-driven fine needle.
      Preliminary results in 13 patients.
AB  - The diagnostic value of percutaneous transthoracic needle biopsy using a newly
      designed, semi-automatic, spring-driven fine needle (Autovac, diameter 0.95 and
      1.2 mm) was assessed in a study of 13 patients with circumscribed pulmonary
      lesions (median diameter 50 mm, range 25-100). In all patients, biopsy specimens
      2-30 mm long, were obtained for histologic examination. Eleven patients had
      malignant lesions, in all these the biopsies showed malignancy, and the tumour
      type was correctly classified in 10 patients. Two patients had benign lesions,
      one of these was correctly diagnosed by histology. One patient developed
      pneumothorax at the biopsy procedure. The Autovac needle combines the safety of
      fine aspiration needles with the qualities of biopsies obtained using larger
      cutting needles.

PMID- 8284526
TI  - Unusual course of pulmonary hypertension of vascular origin.
AB  - We report a boy with an unusual course of pulmonary hypertension of vascular
      origin. He suffered from pulmonary perinatal complications due to a Pierre Robin
      anomaly. Pulmonary hypertension was diagnosed at the age of 18 months. He died
      from progressive right heart failure at the age of 19 years.

PMID- 8284527
TI  - Intractable asthma and mitral stenosis.

PMID- 8284528
TI  - Endobronchial lipomas.
AB  - We report 2 cases of endobronchial lipomas diagnosed by biopsy through a
      fiberoptic bronchoscope. Its endoscopic differences with bronchial adenomas are
      analyzed. Computerized tomography contribution to differential diagnosis with
      other pulmonary tumors is reported. Early diagnosis is advised and the endoscopic
      removal, before pulmonary complications are observed, is thought preferable to
      surgery.

PMID- 8284529
TI  - Pneumatoceles and pneumothorax after Pneumocystis carinii pneumonia.
AB  - Pneumocystis carinii pneumonia (PCP) is common in patients with AIDS. The usual
      chest X-ray pattern is a diffuse interstitial pulmonary infiltrate. Nevertheless,
      unusual roentgenographic forms can appear. A patient with PCP that resulted in
      pneumatoceles and a further pneumothorax is described.

PMID- 8284530
TI  - Mesenchymal cystic hamartoma of the lung.
AB  - We report the case of an asymptomatic 51-year-old man, presenting with chest X
      ray abnormalities consisting in multiple pulmonary nodules; the diagnosis of
      mesenchymal cystic hamartoma of the lung was made by an open lung biopsy,
      revealing both nodules of mesenchymal cells and cysts with a lining of normal or
      metaplastic epithelium. Clinical and pathological characteristics of this rare
      entity are reviewed.

PMID- 8284531
TI  - Pulmonary lymphangiomyomatosis and kidney angiomyolipomas.

PMID- 8284532
TI  - Respiratory function in the perioperative phase of the Harrington operation.

PMID- 8284533
TI  - [Left ventricular wall motion: basic concepts and clinical aspects].

PMID- 8284534
TI  - [Carbonic anhydrase].

PMID- 8284535
TI  - [New technology in oxygen measurement].

PMID- 8284536
TI  - [Management for deep venous thrombosis].

PMID- 8284537
TI  - [Pleural indentation].

PMID- 8284538
TI  - [Determining factors of successful percutaneous transvenous mitral commissurotomy
      and eligible indications for the procedure].
AB  - The aim of this report is to investigate the factors which influence mean left
      atrial pressure (LAP) after percutaneous transvenous mitral commissurotomy (PTMC)
      and the characteristics of patients in whom PTMC is most effective. Fifty one
      patients with symptomatic mitral stenosis underwent PTMC. The patients included 8
      males and 43 females, aged 26-66 years (mean age of 46). These patients were
      classified into two groups according to LAP after PTMC: 31 cases with LAP after
      PTMC of 12 mmHg or less (group A) and 20 cases with LAP after PTMC greater than
      12 mmHg (group B). The patients of group A were younger (44 +/- 6 vs 48 +/- 6
      years, p < 0.05), and had atrial fibrillation (af) less frequently (35 vs 65%, p
      < 0.05), and had mitral valve calcification less frequently (29 vs 65%, p <
      0.01). Before PTMC, LAP (19 +/- 6 vs 23 +/- 5 mmHg, p < 0.01) was lower and
      mitral valve area (MVA) (0.95 +/- 0.24 vs 0.81 +/- 0.15 cm2, p < 0.05) larger in
      group A. Symptoms graded according to the New York Heart Association functional
      classification system were similar in both groups before PTMC. After the
      procedure, final MVA (1.79 +/- 0.69 vs 1.40 +/- 0.50 cm2, p < 0.05) was larger
      and systolic pulmonary artery pressure (32 +/- 9 vs 39 +/- 7 mmHg, p < 0.01)
      lower in group A. Mitral regurgitation > or = 3-grade tended to complicate more
      frequently (3 vs 20%, NS) in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284539
TI  - [A clinical study on asthmatic patients who were readmitted after a short period
      of discharge].
AB  - We conducted a clinical study on asthmatic patients who were readmitted within
      three months of discharge. During twelve years (1979-1991), the number of
      patients who were readmitted within three months was 139 cases (209 episodes) in
      our department. Patients with respiratory diseases made up 53% of the subjects.
      Among patients with pulmonary disease who were readmitted within three months,
      the number of patients with lung cancer was 25 cases and that with bronchial
      asthma 24 cases. Within a month period, the number of readmitted patients with
      bronchial asthma was the largest 59% (19 cases) and the number of patients with
      lung cancer came second (4 cases). As for the characteristics of these asthmatic
      patients, the intrinsic type (15 cases), those with a history of over one year of
      the disease (20 cases), and those with steroid dependency (10 cases) were most
      commonly observed. Readmission occurred frequently between October and April.
      Readmission occurred frequently because of asthmatic attacks due to infection of
      reduction of steroid. Among asthmatic patients who were readmitted within one
      month, the disease severity was mild to moderate in 11 out of 19 patients, but
      there was a tendency for this to become intractable thereafter. It is impossible
      to prevent all patients from seeling readmission within a short period of
      discharge. However, we think the doctor's careful education of the patients is an
      important factor to reduce the early readmission rate of asthmatic patients.

PMID- 8284540
TI  - [The mechanism of pleural liquid transudation and absorption following a new
      hypothesis].
AB  - We have put forward a hypothesis that the pleural fluid is filtered at the
      arterial ends of the pleural blood capillaries and is absorbed mainly at the
      venous ends, partly at the lymphatic channels, as it is in the other tissues.
      Then we have calculated the pleural liquid pressure following the Starling
      equation applying the ordinary value of factors. The result is that the
      calculated pleural liquid pressure is low enough to expand the lung.

PMID- 8284541
TI  - [Effect of continuous intravenous administration of midazolam and ketamine on
      respiratory pattern].
AB  - The purpose of the study was to investigate the effect of continuous IV
      administration of midazolam and ketamine on respiratory pattern in six adult
      volunteers. Midazolam 0.05 mg/kg and ketamine 0.5 mg/kg were given, and then 0.1
      mg/kg/hr for midazolam and 1 mg/kg/hr for ketamine were administered
      continuously. We measured MV, RR and TV (OMR86036), and calculated duty ratio and
      mean inspiratory flow at the level of 0 and 5 cmH2O CPAP during spontaneous
      respiration of air with and without 5% CO2. Each parameter was obtained before
      and 1 hr after the start of IV administration of the drugs. With 5% CO2, MV
      decreased significantly from 15.5 +/- 1.5 l/min to 11.7 +/- 0.8 l/min at 0 cmH2O
      CPAP level and from 15.8 +/- 1.8 l/min to 12.6 +/- 1.5 l/min at 5 cmH2O CPAP
      level, and also mean inspiratory flow decreased significantly from 590 +/- 2
      ml/sec to 421 +/- 30 ml/sec at 0 cmH2O CPAP level and from 606 +/- 53 ml/sec to
      477 +/- 48 ml/sec at 5 cmH2O CPAP level. TV decreased significantly during
      sedation at both CPAP levels with or without 5% CO2, while RR and duty ratio
      tended to increase. It was thought that, when the respiration was stimulated with
      5% CO2, the decrease in mean inspiratory flow greatly contributed to the fall in
      MV during administration of midazolam and ketamine.

PMID- 8284542
TI  - [Effect of enalapril on left ventricular hypertrophy and left ventricular
      function in patients with hypertension].
AB  - The aim of this study was to study the effect of enalapril (E) on left
      ventricular (LV) mass, LV function and blood renin-angiotensin (RA) in patients
      with hypertension. Sixteen hypertensives were included in this study (WHO I 8,
      WHO II 8, 49.5 +/- 10.5 yrs). They were examined for blood pressure and heart
      rate. Chest X-ray film, echocardiography (echo), X-ray computed tomography (CT)
      and RA before and after about 6 months of E administration were studied. The LV
      mass was calculated by CT. The LV function was measured by echo. RAS was
      unchanged during this study. LV mass was significantly reduced after E (121.4 +/-
      25.6 vs 104.6 +/- 13.7 g/cm2). The LV systolic function was unchanged after E,
      but LV diastolic function improved. It was shown that the long-term
      administration of E improves LV hypertrophy and LV diastolic function without any
      change of RAS.

PMID- 8284543
TI  - [Effects of intravenous injection of ioversol, a nonionic contrast medium, on
      circulating blood volume: comparison among different combinations of its dose and
      volume injected].
AB  - Effects on circulating blood volume (CBV) of the intravenous injection of a
      nonionic contrast medium, ioversol, with various doses were assessed in order to
      find a way of injection with less effects on systemic circulation. Ioversol was
      injected as a bolus to 20 mongrel dogs at doses of A: 3.75 ml/kg (n = 8) or B: 2
      ml/kg (n = 6) of a solution containing 320 mg iodine per ml, or C: 2 ml/kg (n =
      6) of a 240 mgI/ml solution. Colloid oncotic pressure (COP) of the bloods drawn
      before and 1, 2, 3, 5 min after the injection of ioversol was measured by a
      needle type osmometer, and changes in CBV were calculated using the COP values.
      Upon injection of ioversol CBV increased rapidly and then gradually returned to
      the preinjection levels. The change in CBV induced by ioversol was significantly
      less than those reportedly induced by an ionic contrant medium, iothalamate, and
      a nonionic medium, iopamidol, and comparable to that by another nonionic medium,
      iohexol. The degree of increase in CBV and the blood concentration of ioversol
      were related to the amount, but not the volume, of ioversol injected. Thus,
      ioversol proved to be one of the low osmotic nonionic contrast media with less
      effects on CBV. Furthermore, it is suggested that the amount, rather than volume,
      of contrast medium should be taken into consideration when the angiography of the
      patients with reduced cardiac function, children or aged patients is performed in
      whom the contrast medium-induced CBV expansion needs to be as less as possible.

PMID- 8284544
TI  - [A case of obstructive sleep apnea syndrome with increased lung water during
      sleep].
AB  - A 22-year-old man was admitted to the department of plastic surgery in our
      university with diagnosis of ankylosis and microgeniea. His complaints were
      snoring and somnolence in the daytime, so we performed a Respigraph (Chest) that
      showed obstructive apnea during sleep. We diagnosed obstructive sleep apnea
      syndrome. So we observed pulmonary circulation and measured lung water using the
      double indicator dilution method (Nihon Koden, MTV-1100) during sleep. During the
      period of apnea, arterial oxygen pressure and mixed venous saturation decreased,
      reversely, mean pulmonary arterial pressure rose, lung water (ETV) and central
      blood volume increased. We considered that the increase of lung water during
      sleep apnea is caused by hemodynamic change due to hypoxia and increase of venous
      return. After operation, the value of blood gas assay and apnea index were
      improved.

PMID- 8284545
TI  - [Transvenous pacemaker implantation for sick sinus syndrome with mirror-image
      dextrocardia].
AB  - A case of sick sinus syndrome with mirror-image dextrocardia which was associated
      with bilateral superior vena cava and an absent inferior vena cava with azygos
      continuation is reported. A 45-year-old woman was referred to our hospital with
      the chief complaints of dizziness and palpitation. The electrocardiogram showed a
      atrial fibrillation with a 4-second period of asystole. A permanent endocardial
      bipolar demand pacemaker was inserted through the left superior vena cava. Since
      anomaly of venous system is commonly associated with mirror-image dextrocardia,
      the angiogram is necessary prior to permanent pacemaker implantation.

PMID- 8284546
TI  - [A case involving coronary dissection caused after PTCA that was observed with
      intravascular echocardiography].
AB  - We encountered a case that was observed on coronary angiography (CAG) during
      coronary dissection after coronary angioplasty (PTCA) in which the dissected
      cavity disappeared on CAG but thrombolytic obstruction in the dissected cavity
      could be observed by intravascular echocardiography (IVUS). A 67-year-old woman
      was admitted with a diagnosis of acute myocardial infarction with ST elevation
      when experiencing chest pain. PTCR was performed for obstruction of the left
      circumflex artery (LCX) and the stenosis was improved to 90 percent. One month
      later PTCA was performed on an obstruction lesion in LCX and the feature of the
      dissected section at the same site was observed by CAG after PTCA. CAG showed
      that the dissected cavity had disappeared a year and a half later, but IVUS
      indicated thrombolytic obstruction in the dissected cavity.

PMID- 8284547
TI  - [A case report of acute mid-graft occlusion of the left internal mammary artery
      to the left anterior descending artery after PTCA].
AB  - A 66 year-old woman underwent coronary artery bypass grafting for postinfarction
      angina. A left internal mammary artery graft was joined to the left anterior
      descending artery. Coronary and graft angiography revealed a 90% stenosis in the
      anastomotic site of the left internal mammary artery. During PTCA with a 2.0 mm
      balloon catheter, acute occlusion of the graft body occurred. Intragraft
      injection of isosorbide dinitrate failed to dilate the graft. Thus, careful
      consideration should be given to several complications such as acute occlusion of
      the graft when PTCA for anastomotic site of the graft is performed.

PMID- 8284548
TI  - [A case of long-standing isolated traumatic tricuspid regurgitation with
      remarkably dilated right cardiac chambers and pancytopenia].
AB  - We report a rare case of tricuspid regurgitation due to nonpenetrating chest
      trauma 33 years previously. A 79-year-old man suffered a blunt trauma due to a
      piece of wood at work in 1958. He suffered multiple rib fractures on the right
      side and was admitted. Since then, he began having shortness of breath on
      exertion and was treated with medication. The patient was transferred to the
      Division of Cardiology, Hakodate National Hospital in 1984. A chest x-ray film
      revealed a marked cardiomegaly. Cardiac catheterization showed severe tricuspid
      regurgitation. Hepatomegaly and pancytopenia was observed. He was readmitted
      because of general fatigue in July 1991. Two-dimensional echocardiography
      demonstrated systolic excursion of septal and posterior tricuspid leaflets with
      ruptured chordae tendineae into the right atrium, and a remarkably enlarged right
      ventricule, right atrium and vena cava interior. Cardiac catheterization was
      performed. The right atrial pressure-wave form resembled the right ventricular
      pressure recording (ventricularization of the atrial pressure). Right ventricular
      cineangiography revealed severe tricuspid regurgitation, grade 4. Laboratory data
      showed pancytopenia. Thrombocytopenia progressed (3 x 10(4)/mm3), and a
      hemorrhagic tendency developed. The liver edge was palpable 4 finger breadths
      below the right costal margin. Pancytopenia due to congestive hepatomegaly and
      hypersplenism would have complicated this case.

PMID- 8284549
TI  - [Mechanisms of electrogenic secretion of potassium in endolymph].
AB  - Endolymphatic potential is assumed to result from active K transport into the
      endolymphatic compartment and passive K diffusion in the opposite direction.
      However, in several in vivo experiments, changes in endolymphatic potential
      differed from that in endolymphatic K concentration. Moreover, in in vitro
      experiments, a negative endolymphatic potential was observed in presence of
      ouabain without K gradient between the two compartments. These observations
      suggest that the coupling between the K transport and the genesis of the
      endolymphatic potential is not tight. Several factors may influence separately
      the endolymphatic potential and the K transport such as the acid-base
      equilibrium, the integrity of the Reissner's membrane, the hormonal status and
      the Na transport.

PMID- 8284550
TI  - Investigations in electrophysiology and morphology of the VIII cranial nerve.
AB  - The morphological and functional changes of the eighth nerve in patients
      undergoing cerebello-pontine angle (CPA) surgery are under investigation in the
      ENT Department of the University of Verona. The main aspects of the research are:
      ultrastructural examination of the eighth nerve in normals and subjects operated
      on for vestibular or cochleo-vestibular neurectomy and for acoustic neuroma;
      monitoring cochlear nerve function during CPA surgery by monopolar and bipolar
      recording of cochlear nerve action potential (CNAPs). The specific aims of this
      research are: to acquire information on the pathophysiology of a number of
      peripheral cochleo-vestibular disorders; to evaluate the role of intraoperative
      recording of the eighth nerve in preserving hearing.

PMID- 8284551
TI  - [Exploration of the efferent system in man: basic and clinical results].
AB  - Since 1989, the exploration of the medial efferent system has been possible in
      human by using a non-invasive technique consisting in the association of the
      contralateral acoustic stimulation and the evoked otoacoustic emissions (EOAEs).
      This exploration presents a great interest for fundamental auditory research
      because it is the sole means of exploring in human these cochlear efferent
      neurons synapsing at the base of the outer hair cells. The function of this
      system is still unknown. The interest of such an exploration in clinical research
      is now becoming obvious such that it would be not only useful but also necessary
      to establish a precise diagnosis in particular pathologies. The aim of the
      present paper is to expose basic results obtained on the medial efferent system
      in normal subjects and above all to present findings for pathological ears, among
      which figure in particular: retrocochlear pathologies, hyperacousia, noise
      induced hearing loss, tinnitus. In addition to the diagnostic interest of the
      exploration of the medial efferent system, a knowledge of its functioning will
      probably allow its role in audition to be determined.

PMID- 8284552
TI  - [Acoustic neuroma].
AB  - The progress of the diagnostic and treatment of the acoustic tumors have begin in
      the years 1960. From this time, radio imaging, surgical and anasthesic techniques
      have improved in such a way that the lethality of the surgery is almost equal to
      0% and the preservation of the facial mimic have reached a point that was never
      attained before. It must be emphasized that this surgery requires a surgical
      staff well trained and an appropriate structure. The preservation of hearing
      remains and will remain possible in some exceptional cases, as we know how
      fragile is this function in most of the cases.

PMID- 8284553
TI  - [Treatment of sudden deafness apropos of 447 cases].
AB  - Due to 447 cases of sudden deafness followed up and treated during the last ten
      years in their clinic, the authors report the results of their treatment method
      composed of normovolemic hemodilution followed by fractional perfusion of
      vasodilators, corticosteroids and anticoagulants. Presenting overall examination
      of this population with audiological, vestibular, clinical, hematological and
      radiological findings, they insist on the need for emergency treatment and
      discuss the different aspects of this problem. They also present a global
      evaluation of the investigations performed on some patient groups. The most
      spectacular recoveries are obtained in cases who present earlier and who have a
      hearing loss of low frequencies.

PMID- 8284554
TI  - [Ototoxicity of aminosides: recent results on uptake and clearance of gentamycin
      by sensory cells of the cochlea].
AB  - Recent experiments using autoradiographic and immunohistochemical labelling of
      gentamicin have demonstrated that GM penetrates specifically into the sensory
      cells of the inner ear, with a good correlation between the intensity of the
      labelling and the respective degrees and localisations of ototoxic damages. In
      the sensory hair cells GM ils localised below the cuticular plate, in an area
      rich in lysosomes during the ototoxic treatment. This penetration precedes the
      development of ototoxicity and there seems to be a threshold of intracellular
      concentration of GM for development of intracellular ototoxic processes.
      Clearance is very slow since GM can still be observed 11 months after the end of
      a non toxic treatment (60 mg/kg/day for 6 consecutive days). This observation is
      of clinical interest, in view of the delayed development of ototoxicity often
      observed clinically, and with respect to other hazards, including new ototoxic
      treatments, to which the cells can be exposed while loaded with the
      aminoglycoside molecule.

PMID- 8284555
TI  - [Application of osseous allografts in surgery of the middle ear. Authors'
      experience].
AB  - The authors describe an osseous allograft enabling reconstruction with or without
      filling of the middle ear cavities in suppurative chronic otitis. This filling
      material is a cryoconserved osseous allograft. It is saturated with an antibiotic
      sensitive to the germs responsible for otorrhea based on the data of the
      antibiotic sensitivity test and is thus adapted to each patient. The technique
      for preparing the material is described. This material was applied to 70
      patients, including some who received the material over four years ago. The
      operation made it possible to stop the infection. The long-term check-ups show
      good tolerance of the material with, nevertheless, a certain amount of resorption
      in some cases.

PMID- 8284556
TI  - [Bone and cartilage allografts in microsurgery of the ear].
AB  - The authors present there experience with bone allografts and costal cartilage
      allografts in middle ear microsurgery. A drastic selection of the doners and a
      careful preparation of the grafts avoid the risk of viral transmission to the
      receiver. The easy available materials can be used for reconstructing the ear
      drum, the ossicular chain and the tympanic bony wall. With good anatomical and
      functional results, even at long-term (3 and 4 years).

PMID- 8284557
TI  - [Laser: otology, oto-neurosurgery].
AB  - The use of lasers in otology is rather recent and their use in otoneurosurgery is
      even more so, as shown by the limited number of publications dealing with this
      subject in the literature. After a review of the main bibliographical data on
      these subjects, the authors present their experience and analyze their results.
      Two types of lasers were used successively, an Argon laser and then a laser with
      a double KTP 532 and Nd: YAG 1320 nm beam. The Argon laser and the KTP 532 laser
      were exclusively used in otology whereas in otoneurosurgery, both KTP 532 and Nd:
      YAG 1320 nm beams were used depending on the indications. The KTP 532 beam
      appears to be preferable for treating vascular and small-sized lesions; the Nd:
      YAG 1320 nm beam proves to be very advantageous for vaporizing the slightly
      vascular, larger lesions such as stage III and IV neurinomas of the VIIth.

PMID- 8284558
TI  - [Prefabricated tympanic prosthesis].
AB  - Total and subtotal perforations of the tympanic membrane cause problems.
      Adhesions and poor hearing results are the outcome when just the stapes or the
      footplate remain intact. Reinforcement of the transplant using cartilage and
      plastic sheeting were not successful in the long run. The tympano-wire prosthesis
      with its concave form prevents the above mentioned disadvantages. Short
      interpositioning is to prefer in order to prevent impedance.

PMID- 8284559
TI  - [Implants for the middle ear, development of a human prototype].
AB  - Middle ear implants are a new type of hearing aid. Their principle is direct
      stimulation of the inner ear fluids, by a vibrator implanted in the middle ear.
      Two technologies are developed by different teams: electromagnetic vibrators, and
      piezoelectric vibrators. Middle ear implants should be partially implantable (P
      MEI), or totally implantable (T-MEI). Authors develop, concurrently with animal
      experimentation an in vitro method to measure the performance date of the
      vibrators. The specifications of a future P-MEI have been defined, and vibrators
      tested with this method. First results encourage to develop this project.

PMID- 8284560
TI  - [Surgery for deafness: tympanoplasty].
AB  - The communicative task of the auditory system is characterized by the perception
      of sound in it's complexity. This holds true especially for verbal communication
      which is the most important part of the condition human of man. Based on these
      thoughts the development of otosurgery up to tympanoplasty is highlighted.

PMID- 8284561
TI  - [Development of the surgery of chronic otitis].
AB  - For on a strictly conceptual level, today as well as yesterday we find the two
      main streams of thoughts shared by otologists. Some put the emphasis on the
      exeresis of lesions which are mainly cholesteatoma, at the agreed expense of
      hearing. Others are anxious to conciliate lesion exeresis and conservation, even
      restoration of hearing. The first streams of thoughts outnumbered the others
      during the first half of the century. Thus that was the triumph of the radical
      mastoidectomy, due to the works of Kurster, Laufal and Stacke, then those of
      Bergman, Barany, Bondy, Beyer and Voss. Today the heirs to that philosophy have
      converted this surgery, in open technique tympanoplasty. In the second streams of
      the ... there was Heath in 1904, then Bondy in 1908, and especially Sourdille in
      France, who in his thesis, described antro-atticotomy with conservation of the
      ossicular chain. The state of mind he was in as early as 1918 makes him one of
      the fathers of tympanoplasty, at least so we think. Unfortunately for him, he was
      ahead of his time and it wasn't until the second half of the century that the
      heirs to his philosophy could fulfill the vow which was to conciliate lesion
      exeresis and restoration of hearing. To be frank, they enjoyed the use of
      antibiotics and surgery microscope, without which tympanoplasty whose initiators
      were Zollner and Wullstein would have never been possible. A lot of improvement
      remains to be done as far as chronic otitis surgery is concerned.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8284562
TI  - [Hypoacusis and tinnitus: an overview].
AB  - An overview of hearing loss and tinnitus deals with the evaluation and
      measurement of auditory function and the factors which influence hearing. The
      change in the threshold of hearing with age shows a basic pattern, which is also
      observed in many auditory disorders. Characteristically, the audiogram is
      bisegmental, with change in threshold being a linear function of log frequency.

PMID- 8284563
TI  - Pediatric surgical oncology. Introduction.

PMID- 8284564
TI  - Supportive care of the paediatric cancer patient.
AB  - Cytotoxic therapy for paediatric malignancy continues to be associated with
      significant mortality and morbidity. However, survival figures continue to
      improve despite increasingly toxic treatment protocols. Aggressive supportive
      care, more than any other modality, has produced a dramatic reduction in
      mortality during the past 30 years, and includes the appropriate management of
      infection, provision of adequate nutrition, and proper use of blood and blood
      products. The paediatric surgeon plays an integral role in the multidisciplinary
      team of cancer management and together with other team specialists is responsible
      for the planning of surgical intervention and also ensuring the safe passage of
      immunologically impaired patients through the additional stress of surgery. This
      paper details essential aspects of supportive care as commonly practiced in
      paediatric patients undergoing therapy and surgery.

PMID- 8284565
TI  - Venous access in pediatric oncology patients.
AB  - Long-term central venous access is an integral part of the management of many,
      but not all children with cancer. The proper selection of those children who
      require this access and which access device (external vs. totally implanted) is
      best suited to that child is important to minimize complications and obtain
      optimal results. Although most of these devices can be expected to last the
      duration of the treatment protocol or the patient's life, complications
      (infection, occlusion, dislodgment) occur with higher than desired frequency,
      infection being the most common. No measures are clearly beneficial in preventing
      infection, but most infections can be treated successfully without device
      removal. Premature removal or dislodgement occurs more frequently with external
      catheters and may be minimized by techniques used at insertion. Occlusion,
      detected early, can be successfully managed by clot lysis in most children.

PMID- 8284566
TI  - Anesthesia considerations for pediatric cancer.
AB  - The multidisciplinary approach to the care of children with cancer demands an
      understanding of all aspects of its treatment. Recognition of potential anatomic
      and physiologic derangements which may result from specific types of malignancy
      allows optimal preoperative preparation. Understanding the anesthetic
      implications of cancer chemotherapy, irradiation and surgery, and the medical
      complications which result, is essential. The anesthesiologist is involved in
      critical perioperative issues during surgical resection in the operating room,
      but just as importantly plays a crucial role in a variety of procedures performed
      in remote locations. An awareness of special problems related to cancer and its
      treatment allows optimal anesthesia care while dealing with such issues as
      radical surgery, organ system failure, acute and chronic pain, and terminal
      illness.

PMID- 8284567
TI  - Radical surgery for abdominal neuroblastoma.
AB  - Radical operation predominantly for those with stages III and IV, i.e., locally
      advanced and/or metastatic abdominal neuroblastoma, is described. Generally the
      surgery has been performed when tumour shrinkage has been achieved by means of
      chemotherapy, and metastases have been ablated. The author compares his results
      in 46 patients with those of 34 patients undergoing less aggressive surgery
      performed by a number of surgeons, with similar results. Given the difficulties
      inherent in performing curative resection for disseminated abdominal
      neuroblastoma, the surgeon needs to be convinced that his/her efforts are
      worthwhile. The results reported here do not provide such reassurance.

PMID- 8284568
TI  - Current biologic and therapeutic implications in the surgery of neuroblastoma.
AB  - Advances in the understanding of neuroblastoma biology have helped distinguish
      those patients who require maximum therapy from those who do not. However,
      management of children with advanced disease remains a significant problem. New
      more intensive multiagent chemotherapy, ablative chemoradiotherapy with bone
      marrow transplantation, radiolabelled monoclonal antibody technology and a host
      of biologic response modifiers are currently being intensively studied.
      Nevertheless, surgery remains crucial for diagnosis, for providing adequate
      tissue for biological and histopathologic staging, for primary and secondary
      resections as well as restaging after therapy. Major surgical questions remain to
      be addressed in cooperative group studies.

PMID- 8284569
TI  - Current management of Wilms' tumor.
AB  - Most children with Wilms' tumor can now expect remarkably good survival. Current
      protocols have placed greater emphasis on reducing the morbidity of treatment for
      low-risk patients reserving intensive treatment for selected high-risk patients.
      This review addresses recent advances and current recommendations for the
      treatment of nephroblastoma. Controversial issues regarding the surgical
      management of these children are also discussed.

PMID- 8284570
TI  - Extremity rhabdomyosarcoma: biological principles, staging, and treatment.
AB  - Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and
      adolescence with 20% of the primary tumors anatomically located on extremities.
      It is a complicated entity that requires careful planning and coordination
      between the surgical oncologist and other members of the therapeutic team for
      successful treatment. Even with the most effective regimens more than 50% of
      patients will die from progressive, usually distant disease. Further progress may
      require new therapeutic agents or techniques. The surgical oncologist is a
      necessary and often prominent member of the team. Elements of the biological
      behavior, histopathology, clinical staging, and treatment of extremity
      rhabdomyosarcomas occurring in children are discussed. In particular, the
      importance of the alveolar subtype in determination of prognostic risk as well as
      new findings regarding the molecular biologic determinants of phenotypic behavior
      are mentioned. Finally, innovative methods of local control like regional
      arterial perfusion and rapid intraoperative brachytherapy are addressed.

PMID- 8284571
TI  - Bladder/prostate rhabdomyosarcoma: results of the multi-institutional trials of
      the Intergroup Rhabdomyosarcoma Study.
AB  - Rhabdomyosarcomas (RMS) occurring in pelvic sites are almost entirely of the
      embryonal histologic subtype and are relatively responsive to chemotherapeutic
      agents. When treated by radical surgery, pelvic irradiation, and intensive
      chemotherapy for 2 years, survival rates of higher than 85% have been achieved.
      However, the effects of such therapeutic approaches have resulted in major
      changes in the quality of life of survivors, because of the loss of pelvic
      organs, primarily the bladder. Current efforts are directed towards achieving
      long range survival with procedures that are less extensive than pelvic
      exenteration or total cystectomy and by regimens that eliminate or reduce the
      intensity of radiotherapy. Until the past 5 years, these efforts have been
      relatively unsuccessful in both North America and Europe. However, the most
      recent studies of the IRS and European cooperative groups suggest that a majority
      of these patients can survive with intact pelvic organs when treated with
      currently available chemotherapeutic agents in conjunction with radiotherapy and
      limited surgery.

PMID- 8284572
TI  - Nonrhabdomyosarcoma in children: prognostic factors influencing survival.
AB  - In approximately 90% of children with nonrhabdo soft tissue sarcoma (NRSTS) local
      control can be obtained by either surgery alone or with supplemental radiation.
      The disease-free survival is, however, only about 50%. To determine factors
      influencing overall survival, we undertook a retrospective review of the 154
      children with NRSTS. We used the American Joint Committee on Cancer staging
      system (1988), using invasiveness, size, and a Pediatric Oncology Group grading
      system. Using this system we documented that 72 (46%) were noninvasive (T1)
      lesions. Of these 72 patients 50 (70%) were < or = 5 cm A, and only 9 (18%) had
      G3 lesions. Overall 7/72 (10%) have died. In contrast to the 82 patients with
      invasive (T2) lesions, 65 (79%) were > 5 cm (B), with approximately 80% G3. Of
      all T2 lesions, 56/82 were G3 (65%). Here, overall 58/82 (70%) have died,
      primarily because 49/58 had G3 lesions. Important prognostic factors include
      primarily G3 lesion 52/71 (73%) mortality, as compared to 13/83 (15%), G1-2
      dying. Children with invasive lesions tended to have larger tumors, 50/65, most
      of which were higher grades. We feel that patients with histologic grade G3 and
      T2 lesions should be enrolled in effective chemotherapy protocols.

PMID- 8284573
TI  - Management of hepatic epithelial malignancy in childhood and adolescence.
AB  - This review addresses the management of epithelial liver tumors of childhood and
      adolescence (hepatoblastoma and hepatocellular carcinoma), which constitute
      approximately 90% of primary liver malignancy in this age group. The
      epidemiology, pathology, clinical presentation, and diagnosis are given in order
      to appreciate differences in biological behavior of these two neoplasms and the
      need for a distinct therapeutic approach to each. The multidisciplinary treatment
      of hepatoblastoma has become increasingly refined and long-term survival can be
      expected in approximately 80% of patients. Where survival once depended solely on
      complete surgical resection, it is now also possible in patients with initially
      unresectable tumors due to effective cytoreductive chemotherapy. The problem of
      systemic relapse following complete surgical resection has been reduced although
      not eliminated by adjuvant chemotherapy programs. To date, the biological
      behavior of hepatocellular carcinoma prohibits complete resection in the majority
      of children and chemotherapy has not been effective. Early detection, development
      of new agents and techniques such as monoclonal antibodies and total hepatectomy
      with autologous transplantation in selected cases may offer hope for the future.

PMID- 8284574
TI  - Changing role of surgery in childhood lymphomas.
AB  - The use of combinations of chemo- and radiotherapy have decreased the need for
      surgical staging of Hodgkin's disease. The goal of decreasing therapy while
      maintaining cure rates, however, recreates a need for staging. Attempts are being
      made to devise criteria to decrease the need for surgical staging or to decrease
      the extent of the procedure. Non-Hodgkin's lymphoma requires adequate tissue
      samples for analysis, for example, for immunophenotyping to determine treatment.
      Surgical resection in non-Hodgkin's lymphoma is inadequate for treatment but may
      be helpful. Debulking, however, is no longer recommended.

PMID- 8284575
TI  - Prognostic factors and relative risk in hypopharyngeal cancer--related parameters
      concerning stage, therapeutics and evolution.
AB  - The prognostic value of 16 parameters was evaluated in a series of 126 squamous
      cell carcinoma of hypopharynx between 1978 and 1985 at the "Servico de Cirurgia
      de Cabeca e Pescoco" of the "Hospital Heliopolis", Sao Paulo. The variables
      considered were: age, sex, ethnic background, interval between diagnosis and
      detection of first symptom, extension of primary lesion (T), N categories,
      histologic evaluation of primary lesion (pT) and neck node metastasis (pN),
      number of clinical positive nodes (NGPOS), radiation, chemotherapy and recurrence
      of the disease (local, regional and distant metastasis). After a multifactorial
      study using Cox life table model (3) and Dixon mathematic-statistical model (8),
      5 of those 16 parameters were found to influence survival, independently. The
      five variables organized according to hypopharynx cancer prognostic significance
      were: age, odynophagia, number of clinical (NGPRE) and histological (NGPOS)
      metastatic lymph nodes and radiation therapy; odynophagia and radiotherapy were
      the variables that decreased the relative risk of recurrence in the survival of
      cancer of the hypopharynx.

PMID- 8284576
TI  - Musculotendinous lengthening of the knee flexors in cerebral palsy. Surgical
      technique.

PMID- 8284577
TI  - Exchange transfusion in newborn infants with perinatal hemolytic disease.
      Efficacy of the procedure.
AB  - A study was conducted on 115 full-term newborn infants with fetal-maternal ABO or
      Rh incompatibility submitted to exchange transfusion (EXT) due to
      hyperbilirubinemia. Donor blood was preserved in sodium citrate-sodium phosphate
      dextrose-adenine (CPDA-1) and stored for a maximum of 48 hours. The volume of
      blood exchange was equivalent to two blood volumes of the infant and the
      procedure took approximately two hours. The following results were obtained with
      respect to bilirubins: 1) EXT let to a 44.03% reduction in indirect bilirubin in
      the ABO group and to a 43.40% reduction in the Rh group, thus demonstrating the
      efficacy of this procedure. 2) EXT was indicated earlier and in the presence of
      lower indirect bilirubin levels in the Rh group, which was also the group which
      required more frequent repetition of EXT (44.40% as opposed to 17.10% for the Rh
      group. 3) In both the ABO and Rh groups, the indirect bilirubin value that most
      closely approached the level for EXT indication was that obtained 3 hours post
      EXT (least significant percent difference).

PMID- 8284578
TI  - Total hysterectomy versus subtotal hysterectomy: which procedure should be
      performed during the pregnant-puerperal period?
AB  - A retrospective study of 40 hysterectomies due to hemorrhage performed at the
      "Hospital das Clinicas, Faculdade de Medicina de Sao Paulo", from January 1978 to
      August 1989 was conducted in order to determine which type of hysterectomy (total
      or subtotal) is better indicated during the pregnant-puerperal period. We
      analyzed operating time, quantity of blood derivatives transfused during the
      intra- and postoperative periods, time of postoperative hospitalization, number
      of intra- and postoperative complications, and deaths. The results did not show
      statistically significant differences between the two types of hysterectomy. We
      conclude that total hysterectomy is preferable in any clinical situation,
      especially in the presence of uterine atony and low implanted placenta.

PMID- 8284579
TI  - Ischemic rest pain of the lower extremities. Treatment with peripheral nerve
      crush.
AB  - The authors report the results obtained from peripheral nerve crushing in the
      treatment of ischemic rest pain and/or trophic lesions of toes and feet. They
      studied retrospectively 102 patients who were submitted to peripheral nerve
      crushing at the "Hospital das Clinicas da Universidade de Sao Paulo" during a
      sixteen-year period, from March 1971 to April 1987. These patients had no other
      choice, either clinical or surgical. The results were evaluated under three
      aspects: elimination of pain, evolution of trophic lesions and postoperative
      complications. The follow-up period varied from 1 month to 6 years (mean of 18
      months). The results showed immediate elimination of pain in 94% of the patients.
      The remaining 6% were reoperated on within 24 to 48 hours, due to technical
      failure in identifying some of the nerves during the first operation. Regarding
      the trophic lesions, in 71% of the patients the results were good and the
      remaining underwent amputation at leg or thigh. The worst results were obtained
      in patients with necrotic lesions (p < 0.05). Three patients presented surgical
      wound dehiscence. The authors conclude that peripheral nerve crushing constitutes
      a valid alternative for a select group of patients with uncontrollable ischemic
      rest pain in the feet.

PMID- 8284580
TI  - Use of videoscopy as an aid in the placement of tissue expanders.
AB  - In this preliminary note the authors describe a new technique consisting in the
      use of videoscopy as an aid in surgery for the placement of tissue expanders in a
      patient with sequelae due to burn scarring on the posterior thorax. The surgical
      steps are described, together with the technical details of the use of the
      videolaparoscopy equipment. The authors discuss the advantages of this new
      technique which permits the use of small routes of approach, perpendicular to the
      expansion area, thus, providing an excellent view with a minimal amount of
      trauma. The method prevents complications such as dehiscence with prosthesis
      exposure and hematomas. A precise dissection of the necessary area can be
      achieved by this technique, a process facilitated by the continuous expansion and
      bulging of the dissected area obtained by controlled injection of carbon dioxide.
      The disadvantages are the high cost of the procedure and the long surgical time.
      The authors emphasize the need for future rationalization of the indications and
      for an appropriate methodology for the procedure.

PMID- 8284581
TI  - Posterior trapezius myocutaneous flap.
AB  - Since last decade, myocutaneous flaps have appeared among the most versatile and
      safest options for the reconstruction of defects caused by large oncological
      resections, in the head and neck area. Undoubtedly, the myocutaneous flap of the
      pectoralis major muscle is the most widespread and accepted, due to the long
      experience obtained through its use. Nevertheless, it presents some restrictions
      related not only to its rotation arch, but also to the esthetic consequences for
      the donor site in females. Over the last years, there has been a growing interest
      in the posterior trapezius myocutaneous flap (PTMF), which proved to be a
      valuable alternative for reconstruction in selected cases. The experience of the
      Department of Head and Neck Surgery, at the University of Sao Paulo Medical
      School-Hospital das Clinicas, using this technique, is reported here in a
      detailed description.

PMID- 8284582
TI  - Corpectomy and anterior plating in cervical spine fractures with tetraplegia.
AB  - Between 1980 and 1989, 68 tetraplegic patients (69 males and 8 females) with
      cervical spine fractures were treated with corpectomy, iliac bone grafting and
      anterior plating. The average age was 27 years (15-58 years). The resected
      vertebrae was C4 in 4 cases, C5 in 24, C6 in 32 and C7 in 8. The injuries were
      classified according to Allen et al. in: compressive flexion in 47 cases,
      vertical compression in 20 and distractive flexion in 1. The neurologic deficit
      was complete in 30 patients and incomplete in 38 patients. The surgery was
      performed 7 days (average) (1-28 days) after the trauma. The mean follow-up was
      2.8 years (1-9 years). In the postoperative period early mobilization was
      permitted with a plastic collar. There were 6 deaths that were not related to the
      technique in the first 4 weeks; the results of the remaining 62 patients are
      presented hereafter. In the final follow-up we observed that 56 patients had no
      complications related to the procedure and the spine was stabilized. The
      following complications were observed in the remaining patients: 5 partial
      loosening of the plate, but the patients were asymptomatic and 1 complete
      loosening that was reoperated after 2 weeks. The motor indices improved from 12.4
      points initially to 23.7 in the complete tetraplegics and from 30.2 points to
      72.5 in the incomplete tetraplegics. We conclude that the anterior plate fixation
      after anterior decompression for cervical spine fractures avoids the extrusion of
      the graft and provides immediate stabilization of the spine, permitting early
      mobilization of the patients.

PMID- 8284583
TI  - Ileal segmental gangrene caused by a metastatic mesenteric carcinoid.
AB  - Malignant tumors of the small intestine are rare and their symptoms are discrete
      and of a chronic nature. At times they manifest as an acute abdomen, with high
      mortality. Carcinoid tumors represent one of the types of intestinal tumors, of
      the neuroendocrine line, more frequently located in the cecal appendix. In the
      small intestine, carcinoid tumors are most often located in the ileum. Carcinoid
      tumors produce several hormonal substances, some of which may induce symptoms
      such as the carcinoid syndrome. Gangrene of the small intestine is a rare
      complication attributed to hormonal substances produced by the tumor which causes
      high mortality rates. We report, here, a case of ileal segmental gangrene with an
      excellent course.

PMID- 8284584
TI  - Possible effect of peptic ulcer upon the biliary tract.

PMID- 8284585
TI  - [Low stage non-Hodgkin's lymphoma: cases studied in 15 years at the HC-FMUSP
      Children's Institute].
AB  - In the recent few years the treatment of the stages I and II of non-Hodgkin
      lymphomas with the simultaneous use of several drugs showed improvement of
      results. In the period between 1977 and 1992 three consecutive chemotherapy
      programs have been developed in the "Instituto da Crianca-HC-FMUSP". Between 1977
      and 1980 five patients belonging to stage II were treated according to the LSA 2
      L-Protocol; complete remission was attained in all of them and three patients
      have been kept in remission so far. In 1980-1984 period a new regimen (Protocol-I
      80) was instituted using the same remission induction strategy as before adding a
      consolidation with Cyclo and Adria combination and a continuation phase with 6
      MP+MTX; five out of six patients have survived free of events till now. In the
      1984-1992 period a new protocol was designed (VM-26+ARA-C) replacing Cyclo+Adria.
      Five patients were included and all of them are disease free survivors.

PMID- 8284586
TI  - [Osteomyoarticular injuries in a physical conditioning program].
AB  - From the follow-up of one hundred and thirty patients in a physical conditioning
      program during the period of one year, partially disabling lesions with
      preliminary complaints were observed at the beginning of the program in thirteen
      patients, and lesions during the development of the program were observed in
      nineteen patients. Within the first group, four patients had to quit the program,
      two temporarily and two definitively. In the second group, five patients had to
      interrupt the program for periods varying from twenty days to two months. In both
      groups, treatment involving physical agents, kinesiotherapy and drugs was
      proposed. Interruptions in the physical conditioning program for periods longer
      than three weeks imply in considerable reduction of the cardiovascular benefits.
      The clinician must be aware of the fact that sedentary patients have not only
      cardiovascular, but also musculoskeletal deconditioning. These patients must be
      evaluated by the physiatrist in order that the disabling lesions be avoided and
      treated.

PMID- 8284587
TI  - [Effect of nutritional support on survival of AIDS-IV C patients].
AB  - Fifty-two patients with AIDS-IV C (opportunistic infections) received nutritional
      supplementation, (enteral diets or total parenteral nutrition) in 60 admission
      episodes. Most patients had lost more than 10% of their ideal weight; albumin
      serum level was inferior or equal to 3.0 g/dl at admission in 33.3% of cases, and
      low serum albumin had a positive correlation with mortality (p less than 0.05%).
      Lean body mass, indirectly evaluated by 24 hour urinary creatinine excretion was
      less than 30% of the ideal in 44.7% of cases, and had a positive correlation with
      death rate. Enteral nutrition was given in 16.7% of episodes, total parenteral
      nutrition in 35% and in the remaining episodes the patient received only oral
      supplements. Patients that received TPN spent more time in hospital than patients
      with enteral nutrition (23.1 more or less 21.3 days against 7.2 more or less 4.8
      days). Patients with AIDS IV C are usually undernourished, have low serum albumin
      and important deficit of lean body mass. Weight loss and low lean body mass are
      associated positively with mortality. Nutritional support had no influence on
      mortality rate.

PMID- 8284588
TI  - [Lyme disease. Report of a case observed in Brazil].
AB  - Lyme disease is an infectious disease caused by spirochete Borrelia burgdorferi
      transmitted by Ixodid tick bite. The geographic distribution of the disease is
      universal, but the disease has not been identified definitely in South America
      yet. We report a probable case of Lyme disease in a woman, living in Jaguare slum
      (Sao Paulo), who showed characteristics skin lesions of erythema chronicum
      migrans, with fever, weakness, headache, muscular pain, cough, arthralgia and
      sensitive radicular neuropathy in the left arm. The sequential serology made by
      ELISA method, using Borrelia burgdorferi whole sonicated antigen from Dr. Allen
      C. Steere laboratory, showed high titers of IgM antibody (1:1600). Because of the
      persistence of high IgM response for two months, we decided to treat the patient
      with tetracycline 2g/day during 10 days and the sorology became negative two
      months. The western blotting confirmed ELISA results showing presence of five
      bands (IgM). This report fulfills CDC criteria for Lyme disease diagnosis.

PMID- 8284589
TI  - [The importance of Strongyloides stercoralis revisited].
AB  - Strongyloidiasis is a worldwide parasitic disease and of great importance in
      Brasil. Among the diverse species of Strongyloides, only the following are of
      importance to man: S. stercoralis, S. fulleborni and S. fullerboni-like.
      Eventhough S. stercoralis is an intestinal helminth, strongyloidiasis is a
      systemic infection that can affect, beside the gastrointestinal tract, lungs,
      CNS, liver and biliary tract, pancreas, genitourinary tract and skin. The great
      majority of cases are asymptomatic, having a chronic and benign course. Among the
      symptomatic subjects, the gastrointestinal and pulmonary symptoms prevail. For
      unknown reasons, strongyloides infection may result in severe, disseminated
      disease. Immunosuppressive, therapy was identified as an important risk factor
      for disseminated illness. Diagnosing strongyloidiasis may be difficult, and
      eventhough the parasitological stool examination is the most used diagnostic
      test, sometimes larvae cannot be identified. Immunodiagnosis is not yet
      assessible for routine usage and is still a subject of research. Thiabendazole
      remains the drug of choice for treatment of strongyloidiasis, but other drugs,
      such as ivermectin, have been used. The purpose of this paper was to review the
      important aspects of the S. stercoralis infection in man.

PMID- 8284590
TI  - [Current risk of AIDS transmission by transfusion].
AB  - Transmission of HIV infection by blood transfusion was first reported in 1982. By
      systematic blood testing of the donors the risk of transmission of HIV by blood
      transfusion has been diminished. In the USA the risk to be infected by HIV with
      blood that was tested negative is about 1/60.000. In Brazil this risk is much
      greater: it is believed that in Sao Paulo the HIV infection occurs in between
      1/2500 and 1/15000 of transfusions.

PMID- 8284591
TI  - [Expectations of patients waiting for ambulatory care at a cardiology hospital].
AB  - A series of 398 patients attended in the outpatients department of a Center for
      heart diseases in Sao Paulo were interviewed by a social worker and a nurse. The
      greatest part of patients (62%) were living in Sao Paulo City, and the remaining
      38% in other Brazilian cities or States. The Department of Internal Medicine of
      the Medical Faculty of Sao Paulo referred 86 (22%) of these patients to the
      Center, while 159 of them did not receive any primary medical attention before
      that. The existence of cardiological care facilities near their homes was not
      know to 287 (72%) of them.

PMID- 8284592
TI  - [Study of morbidity in patients hospitalized at the Clinic Hospital at the
      Medical School of the USP-1989].
AB  - The diagnostic categories of the patients discharged from the "Hospital das
      Clinicas" of the University of Sao Paulo in 1989 were arranged according the
      International Classification of Diseases (I.C.D.) and analysed. In each Group
      sex, age and the reason of discharge or death was indicated. The data concerning
      39,601 cases were provided by the Medical Data Service of the "Instituto Central"
      of the "Hospital das Clinicas". Only the principal diagnosis was taken into
      account. In the "Instituto de Psiquiatria" most the patients (55.4%) were males
      between 20 and 49 years of age. The main diagnostic categories were affective
      psychoses (20.3%), schizophrenic disorders (15%), and disorders related to
      alcoholism (9.5%). The mortality rate was 0.27%. In the "Instituto da Crianca"
      56% of the patients that left the hospital were male children and 45.8% of them
      were less than one year old. Regarding to the diagnostic categories the most
      important one was that of the diseases of the respiratory system with 27.1% of
      cases, followed by that of infectious and parasitic diseases with 16.0% of cases.
      Within the respiratory diseases the most important were the pneumonias caused by
      not specified microorganisms, and within the infectious diseases the most
      important was the diarrhea of presumably infectious origin. The mortality rate in
      this Institute was 9.4%. The "Instituto de Ortopedia e Traumatologia" left 3,825
      patients 61.7% males, and 46.9% of them were aged between 20 and 49 years. The
      greatest number of cases (57.1%) belonged to the Chapter "Injury and Poisoning"
      followed by that of "Diseases of the Muscoleskeletal System" and Connective
      Tissue Diseases (23.5%). In this Institute the mortality rate was 1.2%. From the
      "Instituto do Coracao" 7,194 patients were discharged; 65% of them were males,
      varying their age between 50 and 69 years. The diseases of the circulatory system
      were mostly ischemic heart disease, miocardiopathies and rheumatic heart
      diseases. Mortality rate in this Institute was 10.8%. The "Instituto Central" was
      responsible for 65.6% of all the patients discharged from the "Hospital das
      Clinicas" (26,015 cases). As to the diagnostic categories the predominant chapter
      was that of "Injury and Poisoning" (12.8% of cases) followed by the "Diseases of
      the Digestive System" (10.9%) "Neoplasms" (10.8%) and the "Diseases of
      Circulatory System" (9.2%). The mortality rate in the "Instituto Central" was
      7.2%.

PMID- 8284593
TI  - [Performance of FMUSP graduate students and curricular disciplines evaluation: in
      search of correlations].
AB  - In search of correlation, the performance of graduate students at the Medical
      Faculty of the University of Sao Paulo, established by self-evaluation of the
      students, was compared with curricular performance. There was no statistically
      significant difference between these two ways of analysis.

PMID- 8284594
TI  - Central nervous system involvement in Chagas' disease. An updating.
AB  - A review was made of the available literature on central nervous system (CNS)
      involvement in Chagas' disease. Thirty-one works concerning the acute nervous
      form and 17 others dealing with the chronic nervous form, all presenting
      neuropathologic studies, were critically analysed. Based on this analysis, an
      attempt was made to establish the possible natural history of CNS involvement in
      Chagas' disease. Among others, the following facts stand out: 1) the initial,
      acute phase of Trypanosoma cruzi infection is usually asymptomatic and
      subclinical; 2) only a small percentage of cases develop encephalitis in the
      acute phase of Chagas' disease; 3) the symptomatic acute forms accompanied by
      chagasic encephalitis are grave, with death ensuing in virtually all cases as a
      result of the brain lesions per se or of acute chagasic myocarditis, this being
      usually intense and always present; 4) individuals with the asymptomatic acute
      form and with the mild symptomatic acute form probably have no CNS infection or,
      in some cases, they may have discrete encephalitis in sparse foci. In the latter
      case, regression of the lesions may be total, or residual inflammatory nodules of
      relative insignificance may persist. Thus, no anatomical basis exists that might
      characterize the existence of a chronic nervous form of Chagas' disease; 5)
      reactivation of the CNS infection in the chronic form of Chagas' disease is
      uncommon and occurs only in immunosuppressed patients.

PMID- 8284595
TI  - Chronic gastritis and Helicobacter pylori in digestive form of Chagas' disease.
AB  - Patients with the digestive form of Chagas' disease frequently present chronic
      gastritis. As the microorganism Helicobacter pylori is now accepted as the most
      common cause of human chronic gastritis, the present work was undertaken to
      verify a possible relationship between the presence of this bacterium and
      inflammatory changes of antral mucosa in chagasic patients. Seventeen chagasics,
      with megaesophagus and or megacolon were studied. Fragments from two different
      regions of antral mucosa were obtained by endoscopy, fixed in 4% neutral
      formaldehyde and embedded in paraffin. The sections were stained by haematoxylin
      and eosin for histology analysis, and by carbolfuchsin for H. pylori
      identification. H. pylori was found in 16 (94.1%) chagasic patients, all of them
      presenting chronic gastritis. Superficial gastritis was seen in 9 (52.9%) while
      atrophic gastritis was present in 8 (47.1%) patients. H. pylori was present on
      gastric mucosa of 8 (100%) patients with atrophic gastritis and of 8 (88.8%)
      patients with superficial gastritis. We concluded that the microorganism H.
      pylori should be considered a possible factor connected with the etiopathogenesis
      of chronic superficial and atrophic gastritis frequently observed in patients
      with the digestive form of Chagas' disease.

PMID- 8284596
TI  - Hemolymphatic components in vectors of Trypanosoma cruzi: study in several
      species of the subfamily Triatominae (Hemiptera: Reduviidae).
AB  - The members of the subfamily Triatominae (Hemiptera: Reduviidae) comprise a great
      number of species of medical importance in the transmission of the T. cruzi
      (American trypanosomiasis). The aim of this study was to contribute to the
      knowledge about the chemical composition in proteins, lipids, lipoproteins, and
      carbohydrates of vectors of Chagas' disease corresponding to twelve members of
      the subfamily Triatominae. This study was carried out in ninphs of the fifth
      instar and adult males of the species: T. delpontei, T. dimidiata, T. guasayana,
      T. infestans, T. mazzotti, T. pallidipennis, T. patagonica, T. platensis, T.
      rubrovaria, T. sordida of the Triatoma genus, and D. maximus and P. megistus of
      the Dipatalogaster and Panstrongylus genera respectively. The results show on one
      hand, qualitative differences in the protein composition, and on the other hand,
      similarity in the lipoprotein profiles. Lipids, proteins, and carbohydrates did
      not show significant differences between species or/and stages.

PMID- 8284597
TI  - Respiratory complications in Brazilian patients infected with human
      immunodeficiency virus.
AB  - PURPOSE: To determine how often and by what means an indentifiable pulmonary
      pathogen can be recognized in human immunodeficiency virus (HIV) infected
      patients with respiratory disorders in Brazil, which are the most frequently
      observed microorganisms and what impact specific therapy has on these agents.
      PATIENTS AND METHODS: Thirty-five HIV seropositive subjects with respiratory
      complaints were studied. All patients had a complete history, physical
      examination and blood counts. The pulmonary assessment included chest radiograms;
      sputum examination for bacterial and fungal pathogens; bronchoscopy with
      bronchoalveolar lavage and transbronchial biopsy. Patients with treatable
      complications received standard antimicrobial therapy. RESULTS: One or more
      microorganisms were found in 24 subjects and another 3 individuals showed
      nonspecific interstitial pneumonitis. The sputum examination identified the
      pulmonary pathogens in 7 cases. The bronchoalveolar lavage and the
      histopathologic examination were diagnostic in 14% and 83%, respectively, of the
      28 individuals that were submitted to bronchoscopy. The most frequently
      identified microorganism was P. carinii (55%), followed by M. tuberculosis (41%)
      and cytomegalovirus (8%). The clinical, laboratory and radiographic findings
      failed to distinguish the specific pulmonary pathogens. Twenty-three individuals
      with P. carinii pneumonitis and/or tuberculosis received specific therapy; among
      the evaluable patients the therapeutic response rates were 79% for PCP and 100%
      for TB. CONCLUSIONS: We have determined that tuberculosis, P. carinii and
      cytomegalovirus pneumonitis are the most common respiratory opportunistic
      diseases in Brazilian patients infected with HIV. The histologic evaluation was
      crucial in order to identify the pulmonary pathogens. Tuberculosis in AIDS
      individuals displayed clinical and radiographic findings atypical for
      reactivation disease. However, most of the features observed in HIV infected
      patients had been previously described in infection of the normal host.
      Furthermore, the AIDS subjects showed a good therapeutic response to anti
      tuberculous drugs.

PMID- 8284598
TI  - [Outbreak of classical fever of dengue caused by serotype 2 in Araguaiana,
      Tocantins, Brazil].
AB  - We report the first outbreak of dengue fever caused by dengue 2 (DEN 2) in
      Araguaina, Tocantins State. Four hundred people of 74 families, living at S.
      Joao, Araguaina Sul and Neblina districts were questioned and then bled, in order
      to obtain sera to test for anti-dengue antibodies. If a person was sick, a small
      quantity of blood was collected for virus isolation. The main clinical picture of
      disease was characterized by fever, headache, myalgias, arthralgias and skin
      rash. Were obtained 1,105 (56 females and 45 males of Culex quinquefasciatus and
      567 females and 437 males of Aedes aegypti) mosquitoes from larvae collected in
      Araguaina. The females of Aedes aegypti obtained from larvae were allowed to feed
      on 8 febrile patients. The diagnosis of infection was made by both virus
      isolation into Aedes albopictus (C6/36) cells, and serology, by Hemagglutination
      inhibition (HI) and IgM capture ELISA (MAC ELISA). No virus was isolated from
      mosquitoes. Although five strains of DEN 2 were obtained from humans, and another
      111 infections were diagnosed serologically (IgM positive). The positivity rate
      of the samples was 27.75% (111 of 400), while that of the families was 66.2% (45
      of 72), where at least one member of the each family was infected. It was also
      detected 26.1% of asymptomatic infections. All age groups were affected.
      Therefore, the infection was more frequent in females (33.5%) than males
      (23.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284599
TI  - Dengue epidemic in the state of Rio de Janeiro, Brazil: virological and
      epidemiological aspects.
AB  - Laboratory studies were carried out on 3178 patients with signs and symptoms
      suggestive of dengue infection from April 1986 to December 1987 in the State of
      Rio de Janeiro, Brazil. The epidemic had two peaks following the first virus
      isolation and affected the inhabitants of 17 counties. Both sex and all age
      groups were affected. Dengue virus type 1 was isolated from 1039 sera and the
      number of confirmed cases was increased to 1874 (59%) by MAC-ELISA. Isolation
      rate confirmed cases reached 80% in the specimens obtained until the 4th day
      after the onset of disease and viraemia ranged from 10(3.0) to 10(8.5) TCID50/ml.

PMID- 8284600
TI  - [Hydatidosis immunodiagnosis: determination of Taenia crassiceps cysticerws
      antigens in hydatid and vesicular fluid].
AB  - The specificity and sensitivity of the enzyme immunoassay (EIA), presently used
      in South America areas where hydatidosis caused by Echinococcus granulosus is
      endemic, was compared to two alternative EIA. One of these uses an hydatid
      antigen of different preparation and the other vesicular fluid of Taenia
      crassiceps cisticerci (VFCC). The effect of previous neutralization in the serum
      sample of antibodies antinormal ovine or murine sera and antiphosphorylcholine on
      the diagnostic efficiency of these EIA was studied. The frequency of distribution
      of the titers obtained with normal sera, hydatid sera positive to DD5 test and
      hydatid sera negative to DD5 test in three EIA systems was analyzed. Results
      showed a significant decrease of sensitivity of the EIA using VFCC when compared
      to these EIA using hydatid antigens. This makes inconvenient the use of VFCC for
      the immunodiagnosis of hydatid disease. No significant differences between the
      two EIA using hydatid antigens were observed. SDS-PAGE analysis showed remarkable
      differences between the VFCC and the hydatid antigens composition and some
      differences among these latters probably due to manufacturing procedures.

PMID- 8284601
TI  - [Value of direct and indirect diagnostic methods in systemic mycoses associated
      with AIDS].
AB  - One hundred and seventeen patients suffering systemic mycosis and AIDS were
      studied during 5 years in the Muniz Hospital of Buenos Aires City. Seventy four
      of them presented cryptococcosis, 39 histoplasmosis and 4 both mycoses. The
      following specimens were studied for the diagnosis: skin and mucous membrane
      scrapings, bone marrow aspirations, bronchial secretions, biopsies of different
      organs, cerebral spinal fluid and blood cultures. Sera were also collected for
      serologic tests. A total of 203 samples from patients with histoplasmosis were
      studied, 46.3% of them showed H. capsulatum in microscopic examinations or in
      cultures, skin scraping was the most sensitive diagnostic method (94.7% of
      positive results), followed by biopsies (80%) and bone marrow cultures (42.1%).
      Specific antibodies were detected in 45.4% of the patients with histoplasmosis,
      using 2 different antigens and 3 types of serologic reactions (complement
      fixation test, immunodiffusion and counterimmunoelectrophoresis). A total of 413
      samples from patients with cryptococcosis were examined, 69% of them confirmed
      the diagnosis. The mycologic study of CSF was the most sensitive method of study,
      since it registered positive results in 89.5%, followed by blood cultures
      (61.2%), skin scrapings (42.9%), and urine cultures (41.7%). Polysaccharyde
      antigens from C. neoformans in organic fluids were detected in almost all the
      cases. The aim of this study is to compare all the suitable diagnostic methods
      which can be used in systemic mycosis associated with AIDS in order to find the
      most rapid way of diagnosis.

PMID- 8284602
TI  - Simplified fluorescent inhibition microtest for the titration of rabies
      neutralizing antibodies.
AB  - A simplified fluorescence inhibition microtest (SFIMT) was standardized for the
      evaluation of antirabies serum neutralizing antibodies based on the rapid
      fluorescent focus inhibition test (RFFIT) and the fluorescence inhibition
      microtest (FIMT). The simplified test showed reproducibility similar to that of
      the FIMT with advantages as easier executation and quicker reading. A simple pre
      treatment of Brazilian microplates produced for immune enzymatic assays (PROSIL)
      gave equivalent results and substantial coast reduction, in relation to imported
      plates (DIFCO). The simplified test can be easily implemented in less
      sophisticated laboratories, as alternative to the mouse serum neutralization
      test, still the most largely employed in Brazil, or even to others as RFFIT and
      FIMT.

PMID- 8284603
TI  - [Evaluation of 3 therapeutic schedules with N-methyl-glucamine antimonate in the
      treatment of visceral leishmaniasis in the state of Para, Brazil].
AB  - We have evaluated, in a retrospective manner, three chemotherapeutic schemes with
      meglumine antomoniate (Glucantime) use in the treatment of 43 autochthonous cases
      of visceral leishmaniasis in children in the age-group of 1-12 years old, during
      the period 1985-1990. Of the 43 cases, 28 (group A) were treated with 40mg/SbV/kg
      given IV at intervals of 48 hours, in courses of 15 applications (scheme I); 8
      (group B) were treated with 40 mg/SbV/kg given IV daily during 15 days (scheme
      II), and 7 (group C) were treated with 20 mg/SbV/kg given IV daily during 15 days
      (scheme III). With the criteria for cure based essentially on clinical
      examination, we admitted that the scheme III would be the preferred for these
      reasons: a) it produces the same cure-rate as those schemes which use double this
      dosage, b) in relation to positive results it is less expensive, c) the scheme
      can be used for more extended periods, with less risk of toxic effects, and d)
      there has till now been no evidence of the development of resistance to treatment
      using this scheme, at least in our particular area of study (Para).

PMID- 8284604
TI  - [Chemoprophylactic activity on Schistosomiasis mansoni of soaps containing
      essential oil from the fruits of Pterodon pubescens].
AB  - The chemoprophylactic action of the essential oil of the fruit of Pterodon
      pubescens Benth (Leguminosae), incorporated in different soap formulations, was
      studied in experimental schistosomiasis. The formulations were used locally on
      the tails of mice which were exposed to Schistosoma mansoni cercariae
      immediately, 24, 72 or 168 hours later by the method of tail immersion.
      Protection was evaluated 45 days after exposure when the mice were sacrificed and
      the worms collected by perfusion. The results showed levels of protection varying
      from 0.0 to 100% depending on the formulation used. A methodology that allowed
      the evaluation of soap protection of mice exposed to natural infection in snail
      infested streams on the outskirts of Belo Horizonte, MG, was also developed.
      Promising results were obtained in that protection of between 57.5 and 31.1% was
      observed in field trials when soap was applied to the animals 24 and 48 hours
      earlier. Preliminary studies evaluating irritation and toxicity were favorable
      and showed that this new prophylactic weapon could contribute to the control of
      schistosomiasis.

PMID- 8284605
TI  - Evaluation in white mice of the infectivity of eggs of Lagochilascaris minor
      (Nematoda: Ascarididae), incubated by decortication with sodium hypochlorite
      (NaOCl).
AB  - White mice were used to study the infectivity of the eggs of Lagochilascaris
      minor Leiper, 1909 after incubation in liquid media, with or without preservative
      substances. Potassium bichromate (K2Cr2O7) at 1% restrict hatching, while 1%
      formalin gave a greater larval yield. Incubation of eggs in distilled water, in
      Roux or Falcon flasks gave a good yield, whether the eggs were obtained from
      human feces or from experimentally infected cats. Treatment of eggs with Sodium
      hypochlorite (NaOCl) at 5.25% for 2 min prior to inoculation, produced a notable
      increment of the larval yield in the infections.

PMID- 8284606
TI  - Mycetoma by Nocardia asteroides: a 9 year follow-up.
AB  - An extensive and severe actinomycetoma by Nocardia asteroides, a rare etiologic
      agent of this infection in Brazil, observed during a 9 year follow-up is
      reported. Unsuitable social and financial conditions led to amputation as the
      only possible solution for this case, no signs of infection relapse having been
      observed in three years after his surgery.

PMID- 8284608
TI  - IgA deficiency associated with human immunodeficiency virus infection.

PMID- 8284607
TI  - Trypanosoma cruzi meningoencephalitis and myocarditis in a patient with acquired
      immunodeficiency syndrome.
AB  - We report the case of a 52-year-old male heterosexual patient with acquired
      immunodeficiency syndrome (AIDS) and reactivation of Chagas' disease manifested
      by meningoencephalitis and myocarditis, diagnosed post-mortem. Unexplained
      reactivation of Chagas' disease should be included among the diagnostic criteria
      of AIDS in human immunodeficiency virus positive patients. On the other hand,
      AIDS should be considered in the differential diagnosis of patients with
      unexplained reactivation of Chagas' disease.

PMID- 8284609
TI  - Isosporiasis in Venezuela: a report of two cases in patients with acquired
      immunodeficiency syndrome.

PMID- 8284610
TI  - [Primary nursing care. A study in the province of Huesca].

PMID- 8284611
TI  - [The prevention of a subcutaneous hematoma by fibrinolysis].

PMID- 8284612
TI  - [Nursing students and health promotion].

PMID- 8284613
TI  - [A view of the current state of nursing].

PMID- 8284614
TI  - [Without continuing education, professional development does not exist. IDER and
      B. Braun Medical, S.A. are starting a collaborative project. The Institute for
      the Development of Nursing].

PMID- 8284615
TI  - [Acceptance of Coloplast:Alterna 3-piece among health professionals].

PMID- 8284616
TI  - [The terminal patient].

PMID- 8284617
TI  - [Childhood tuberculosis. An analysis of the sources of contagion].

PMID- 8284618
TI  - [Urinary infections. The role of nursing].

PMID- 8284619
TI  - [Anxiety in nursing professionals].

PMID- 8284621
TI  - [Schools, should they offer a professional or a postgraduate degree?].

PMID- 8284620
TI  - [Nitrites and nitrates in food].

PMID- 8284622
TI  - Potential of measurements of unsaturated vitamin B12-binding capacity in serial
      colonoscopic biopsy specimens for global and regional assessments of disease
      severity in inflammatory bowel disease.
AB  - We investigated whether measurements of unsaturated vitamin B12-binding capacity
      (UBBC), in homogenates of serial colonoscopic biopsy specimens, could be used as
      objective measures of disease severity in ulcerative colitis (UC) and Crohn's
      disease (CD). On a regional basis UBBC activity correlated with and showed good
      agreement with endoscopic and histologic activity scores (r = 0.8 and 0.6,
      respectively, for UC, and r = 0.7 and 0.7, respectively, for CD). For global
      assessment aggregate UBBC, endoscopic and histologic scores were compared with
      standard clinical activity scores. In UC, correlations with the van Hees index
      were r = 0.7, 0.8, and 0.7, respectively, and UBBC assays accurately reflected
      both regional and global disease activity. In CD, correlations with the CDAI were
      -0.1, 0.7, and 0.6, respectively. Thus, aggregate UBBC scores failed to reflect
      disease activity in CD, in which focal deep ulcers may produce high symptom
      scores but in which adjacent specimens may show no acute inflammation.

PMID- 8284623
TI  - Determinants of symptoms suggestive of gastroesophageal reflux disease in the
      elderly.
AB  - The study material consisted of 487 subjects from a stratified random sample of
      the non-institutionalized population of Turku aged 65 years or more (n = 24,937).
      The study was based on a population study on health status and sleeping habits of
      the elderly. Information on health status and medications was obtained by means
      of interviews and from the national health insurance records of the subjects. A
      postal questionnaire inquired about symptoms suggestive of gastroesophageal
      reflux disease (GERD). In univariate analyses, perceived poor health, insomnia,
      disability, depression, previous peptic ulcer, cholelithiasis, and bronchial
      asthma were associated with daily symptoms suggestive of GERD. Moreover, the
      symptoms were associated with the use of beta-blocking agents, benzodiazepines,
      and neuroleptic agents. In multivariate analyses, previous peptic ulcer,
      perceived poor health, insomnia, and use of benzodiazepines were independently
      associated with symptoms suggestive of GERD. In conclusion, the determinants of
      symptoms suggestive of GERD in the elderly differ from those reported in young
      and middle-aged subjects.

PMID- 8284624
TI  - Does physiologic gastroesophageal reflux affect heart rate or rhythm?
AB  - An acid-induced, cholinergic esophagocardiac reflex has been observed in humans.
      Decrements of heart rate can be induced by direct intraesophageal acid infusion.
      To ascertain whether this reflex occurs during physiologic reflux and whether
      stimulation of this reflex might precipitate dysrhythmias, a prospective study
      was performed. Twenty consecutive patients referred for 24-h ambulatory
      intraesophageal pH monitoring underwent simultaneous 24-h cardiac holter
      monitoring. Analyses were performed only on gastroesophageal reflux episodes
      which resulted in esophageal acidification to pH < 4 for 60 sec or more.
      Evaluable cardiac holter variables included premature ventricular contractions
      (PVCs), premature atrial contractions (PACs), tachycardia (heart rate, >
      110/min), and bradycardia (heart rate, < 50/min). Measurements were made for 60
      sec before and after onset of esophageal acidification. No relationship was noted
      between physiologic episodes of gastroesophageal reflux and PVCs (p = 0.29), PACs
      (p = 0.12), tachycardia (p = 0.33), or bradycardia (p = 0.78). No statistically
      significant correlations were noted between total 24-h acid exposure
      (minutes/24h) and mean heart rate (p = 0.07), number of PVCs (p = 0.41), and
      number of PACs (p = 0.39). Analyses of reflux episodes lasting more than 5 min
      with intraesophageal pH < 2 also failed to show changes in pulse rate (p = 0.22).
      Physiologic gastroesophageal reflux does not induce changes in heart rate or
      rhythm in humans. It is possible that esophagocardiac reflexes noted during
      intraesophageal acid infusion are related to lower pH values or to other factors
      such as osmolarity, temperature, or site-specific receptors.

PMID- 8284625
TI  - Detection and management of common bile duct stones in the era of laparoscopic
      cholecystectomy.

PMID- 8284626
TI  - Efficacy and side effects of a triple drug regimen for the eradication of
      Helicobacter pylori.
AB  - One hundred consecutive patients with Helicobacter pylori infection, as proven by
      culture, were treated with 120 mg colloidal bismuth subcitrate (CBS) four times
      daily, 250 mg tetracycline four times daily, and 250 mg metronidazole four times
      daily during 15 days. The patients were amply instructed in how to take the
      medicine and strongly urged to complete the prescribed course. In 66 of the 100
      patients pretreatment metronidazole susceptibility was determined. Endoscopy was
      performed 3 months after cessation of treatment to check for H. pylori
      eradication by culture, urease testing, and histology. Side effects of the
      treatment were registered and classified into five groups on the basis of
      severity. Eradication was achieved in 93 of 100 patients (93%), in 61 of 62
      patients with a metronidazole-sensitive strain (98.4%), and in 2 of 4 patients
      with a metronidazole-resistant strain (50%). Eighty-two per cent of the patients
      experienced no or just minor side effects; 15% had moderate side effects, and
      just 3% had severe side effects. Non-ulcer dyspepsia patients reported
      significantly more side effects than patients with peptic ulcer disease. With
      proper patient instruction, this treatment regimen is well tolerated and very
      effective for the eradication of metronidazole-sensitive H. pylori strains.

PMID- 8284627
TI  - Treatment of Helicobacter pylori reduces the rate of rebleeding in peptic ulcer
      disease.
AB  - BACKGROUND: We evaluated whether therapy designed to eradicate Helicobacter
      pylori infection resulted in a reduction in rebleeding in patients with peptic
      ulcer disease. Patients presenting because of major upper gastrointestinal
      hemorrhage from peptic ulcer and whose ulcers healed in a study in which they
      were randomized to receive ranitidine alone or triple therapy plus ranitidine
      were followed up regularly with endoscopy. No maintenance anti-ulcer therapy was
      given after ulcer healing. METHODS: Patients received ranitidine, 300 mg, or
      ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g;
      metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth
      per tablet), and was administered for the first 2 weeks of treatment; ranitidine
      therapy was continued until the ulcer had healed or 16 weeks had elapsed. After
      ulcer healing, no maintenance antiulcer therapy was given. Development of ulcer
      recurrence with or without recurrent upper gastrointestinal bleeding was
      evaluated. RESULTS: Thirty-one patients with major upper gastrointestinal
      bleeding from peptic ulcer were studied; 17 received triple therapy and 14
      ranitidine alone. Major rebleeding occurred significantly (p = 0.031) more often
      in those in the ranitidine group (28.6%), compared with none (0%) in the triple
      therapy group. CONCLUSION: Eradication of H. pylori infection reduces the rate of
      ulcer recurrence and rebleeding in complicated ulcer disease.

PMID- 8284628
TI  - Motility-related cyclic fluctuations of interdigestive gastric acid and
      bicarbonate secretion in man. A source of substantial variability in gastric
      secretion studies.
AB  - The relationship between interdigestive gastric motility and secretion was
      studied in eight healthy volunteers. Acid and bicarbonate output rates were
      measured with a high time resolution, using a perfusion system based on
      continuous registration of pH and PCO2 of gastric effluent. Antral pressure was
      measured by manometry. The total duration of the interdigestive motility cycle
      (time between two phase-III complexes) was 96 +/- 12 min (mean +/- SE). In late
      migrating motor complex phase II, acid output, bicarbonate output, and bile
      reflux increased significantly. Acid secretion reached a peak in association with
      motor phase III. The gastric lumen was then rapidly alkalinized; this phenomenon
      was due to a simultaneous decrease in acid secretion and a short-lasting (15 +/-
      2 min, mean +/- SE) phasic increase in bicarbonate output, which was not
      associated with bile reflux (bilirubin). After these phase-III-related events
      both acid and bicarbonate output rates reached a relatively stable level during
      phase I and early phase II. This period of stability constituted 47 +/- 3% (acid)
      and 41 +/- 6% (bicarbonate, means +/- SE), respectively, of the cycle. The peak
      to base line output ratio was 6.6 +/- 1.2 (p < 0.001) for acid and 2.8 +/- 0.3 (p
      < 0.001) for bicarbonate (means +/- SE). The results show a marked variability in
      acid and bicarbonate output rates during the interdigestive motility cycle. The
      magnitude of this variability has previously been underestimated owing to poor
      time resolution of the secretion measurements. If not taken into account, these
      'spontaneous' secretory variations may constitute a considerable source of error
      in gastric secretion studies.

PMID- 8284629
TI  - Postoperative course of functional and cellular variables in liver resection.
AB  - The determination of total serum bile acids (BA) is a sensitive variable for
      detection of altered liver function. This study investigated the course of serum
      bile acids in 44 liver-resected patients with different factors possibly
      compromising liver function. These factors were 1) amount of resected parenchyma;
      2) duration of intraoperative ischemia; and 3) patient's age. The course of BA
      was compared with that of transaminases, bilirubin, lactate, and NH3. Serum BA
      showed a course correlated to the amount of resected liver parenchyma and
      differentiated between groups with < or = 35% and > 35% resected parenchyma.
      Whereas BA were more accurate in paralleling the resected tissue in the first
      postoperative days, a rise of bilirubin indicated complications in the
      postoperative course. As BA did not increase in a case of pulmonary-induced
      multiorgan failure, the specificity of this variable for liver function is
      implied. Different amounts of resection could not be distinguished by
      determination of transaminases. Different ischemic periods did not result in
      significant differences in the postoperative course of BA or bilirubin. However,
      marked elevations of transaminases depending on the duration of hepatic inflow
      occlusion were seen. None of the traced variables were related to the patient's
      age.

PMID- 8284630
TI  - Large-bowel mucosal biotransformation activity in persons at high risk for
      colorectal cancer. A preliminary report.
AB  - The transformation of xenobiotics and endogenous compounds to active carcinogens
      and their subsequent deactivation as an aid to eradication may be important in
      the etiology of some gastrointestinal cancers. In mammals the gastrointestinal
      tract has been shown to be an important site of inducible enzyme systems active
      in mucosal biotransformation, but few data are available in man. The mucosal
      activity of CYPIA1 (formerly aryl hydrocarbon hydroxylase), a potential
      carcinogen-activating enzyme, and catechol-O-methyl transferase, a potential
      carcinogen-inactivating enzyme were determined in colonic tissue obtained by
      biopsy. There were no significant differences in activity rates in normal mucosa
      between colorectal cancer and healthy persons, but significant differences are
      seen in patients with a history of neoplasia with no evidence of recurrence. The
      levels of activity of these carcinogen-inductive and -protective enzymes may be
      prognostic markers, in that the balance or imbalance could play a role in the
      recurrence of neoplasia. This will require confirmation and prospective studies.

PMID- 8284631
TI  - Reduced accuracy of 14C-D-xylose breath test for detecting bacterial overgrowth
      in gastrointestinal motility disorders.
AB  - The accuracy of the 14C-D-xylose breath test in the diagnosis of small-bowel
      bacterial overgrowth was prospectively evaluated in 10 patients with motility
      disorders: 6 myopathic, 3 neuropathic, and 1 mechanical obstruction. Six of the
      10 patients had small-bowel bacterial overgrowth (> or = 10(5) colony-forming
      units/ml) on culture of small-bowel aspirate. Increased breath 14CO2 levels were
      documented in three of six patients with positive cultures and in two of four
      with negative cultures. Two patients with positive results by both methods and
      one of two patients with positive breath 14CO2 but negative cultures had
      previously undergone gastric surgery. Three patients with myopathic dysmotility
      had positive cultures but negative breath tests. Cultures of duodenal aspirates
      and the D-xylose test had sensitivities of 80% and 40%, respectively, for the
      finding of hypoalbuminemia. Compared with cultures, the sensitivity and
      specificity of the breath test were 60% and 40%, respectively. Impaired delivery
      of 14C-D-xylose for bacterial metabolism may result from postprandial antral
      hypomotility (n = 4) or low-amplitude (n = 6) small-bowel motility, contributing
      to the false-negative breath tests. Thus, culture is the optimal method to detect
      small-bowel bacterial overgrowth in patients with motility disorders.

PMID- 8284632
TI  - Efficacy of sucralfate in treatment of non-ulcer dyspepsia. A double-blind
      placebo-controlled study.
AB  - The object of this study was to assess the efficacy of sucralfate in the
      treatment of non-ulcer dyspepsia (NUD). The diagnosis of NUD was made by
      exclusion. All patients underwent an upper gastrointestinal endoscopy and
      abdominal ultrasound, and blood tests were done as clinically indicated. Patients
      with a history of peptic ulcer disease were not included. Symptomatic assessment
      was made at the beginning and at the end of the study. The patients registered
      their most prominent dyspeptic symptoms and whether they improved, were
      unchanged, or worsened. The study was double-blind. Placebo or 1 g sucralfate
      four times daily was given for 3 weeks. Over a 2-year period 104 patients were
      included in the study; 56 received sucralfate and 48 placebo. Nine patients were
      excluded because of poor compliance or side effects, six from the sucralfate
      group and three from the placebo group. The sucralfate and placebo groups were
      comparable with regard to symptom and clinical variables. Global assessment of
      symptoms showed that in the sucralfate group 34 improved (68%), 11 were
      unchanged, and 5 were worse. In the placebo group 31 improved (69%), 11 were
      unchanged, and 3 were worse. There was no statistically significant difference
      between the groups. The 3-week course of sucralfate in patients with NUD did not
      show symptomatic improvement over placebo.

PMID- 8284633
TI  - Parietal cell antibodies among Peruvians with gastric pathologic changes.
      Gastrointestinal Physiology Working Group.
AB  - Parietal cell antibodies were present in 12% of 272 Peruvians presenting for
      endoscopy. Gender, age, socioeconomic status, ethnic background (Peruvian versus
      Japanese), and altitude at which the patient lived were not associated with the
      presence of parietal cell antibodies. No significant relationship could be shown
      between the presence of parietal cell antibodies and either Helicobacter pylori
      infection or gastric lesions, including chronic atrophic gastritis. Loss of
      proper gastric glands was significantly more common in patients who had H. pylori
      infection than in those in whom no H. pylori was found on biopsy (78 of 114 (85%)
      versus 14 of 36 (39%); p = 0.002). Our data suggest that, although parietal cell
      antibodies are present in third-world populations, they are unrelated to H.
      pylori infection and that pathologic changes associated with this infection are
      not mediated by the action of parietal cell antibodies on the cells of the
      stomach.

PMID- 8284634
TI  - Long-term omeprazole therapy does not affect Helicobacter pylori status in most
      patients.
AB  - Fifty-one patients were treated with 20-60 mg omeprazole for reflux oesophagitis
      resistant to H2-blocker therapy during a mean of 49 months of follow-up. With use
      of a standardized enzyme-linked immunosorbent assay technique specific IgG and
      IgG Helicobacter pylori antibodies were determined in serum obtained at the start
      of therapy and at the most recent visit. At the start of therapy 26 patients
      (51%) had evidence of H. pylori infection, as demonstrated by increased IgG and
      IgA antibody levels. During follow-up, 4 of these 26 patients (15%) became H.
      pylori seronegative. It is concluded that long-term treatment with omeprazole has
      no effect on H. pylori status in most patients.

PMID- 8284635
TI  - The influence of cholestasis on CA 50 and CA 242 in pancreatic cancer and benign
      biliopancreatic diseases.
AB  - The tumour markers CA 50 and CA 242 were determined in serum from 70 cholestatic
      patients--35 with pancreatic cancer and 35 with benign biliopancreatic diseases.
      Both markers correlated (r = 0.37) with serum bilirubin in all patients. When the
      patients were subdivided into groups, the only correlation apparent was between
      CA 50 and bilirubin in patients with benign diseases (r = 0.40). The serum
      concentrations of both markers were much higher in patients with pancreatic
      cancer. Serial sampling before and after decompression of the cholestasis showed
      reduction of CA 50 and CA 242 concurrently with bilirubin and alkaline
      phosphatases in nine patients with benign disease but unchanged levels in six
      cancer patients. When the two markers were compared, sensitivity was superior for
      CA 50 (94% versus 73%), whereas specificity was better for CA 242 (65% versus
      34%), as was positive prediction (76% versus 59%), whereas negative prediction
      was higher for CA 50 (86% versus 61%). Higher cut-off levels yielded better
      specificity for CA 50 but not for CA 242. Both markers indicate pancreatic cancer
      irrespective of cholestasis, but moderate elevations occur in some patients with
      benign disorders.

PMID- 8284636
TI  - Hypercholecystokininemia produced by pancreaticobiliary diversion causes gastrin
      like effects on enterochromaffin-like cells in the stomach of rats subjected to
      portacaval shunting or antrectomy.
AB  - Gastrin and possibly cholecystokinin (CCK) control the activity and growth of the
      histamine-containing endocrine cells, the enterochromaffin-like (ECL) cells, in
      the oxyntic mucosa of the rat. Portacaval shunting (PCS) is known to activate the
      ECL cells through as yet unknown mechanisms. PCS also exaggerates the ECL cells'
      response to gastrin, whereas antrectomy causes hypotrophy and hypoplasia of the
      ECL cells. A recent study showed that the ECL cells failed to respond to
      sustained hyperCCKemia caused by pancreaticobiliary diversion (PBD). In the
      present study we investigated whether PBD-produced hyperCCKemia influenced the
      effects of PCS or antrectomy on the ECL cells. The results show 1) that
      hyperCCKemia raised the histidine decarboxylase (HDC) activity of the ECL cells
      in PCS rats but not in control rats, and the CCK-A receptor blockade failed to
      prevent the enzyme activation; and 2) that PBD prevented the ECL cell hypoplasia
      and the decrease in HDC activity induced by antrectomy. The findings suggest that
      under special circumstances endogenous CCK may stimulate the ECL cells.

PMID- 8284637
TI  - Breath methane excretion and intestinal methanogenesis in children and adults in
      rural Nigeria.
AB  - Breath methane excretion was measured in 274 healthy subjects from 2 rural
      communities in northern Nigeria. Studies in 24 adults showed a normal faecal
      flora with no enteric pathogens. Breath methane was detected in 122 (77%) of 159
      adults, 19 (40%) of 47 older children (2-6 years), and 4 (8%) of 68 young
      children (< 2 years). Women were slightly more commonly breath methane-positive
      than men (82% versus 75%, respectively). Hyperventilation did not influence the
      specificity of the breath methane assay, although levels were circa 30% lower
      after deliberate hyperventilation. Methanogens were estimated by enrichment
      culture of faeces from 49 subjects. Of the subjects 76% had faecal methanogens
      estimated at > or = 10(2)/g, 45% at > or = 10(4)/g, and 16% at > or = 10(6)/g.
      There was no significant difference in distribution of methanogenic cultures
      between different age or tribal groups, and there were no obvious correlations
      between breath methane excretion and either the faecal carriage of methanogens
      per se or numbers present.

PMID- 8284638
TI  - Does antral distension inhibit gastric acid secretion or stimulate bicarbonate
      secretion in 'healthy' subjects?
AB  - The effects of a 150-ml antral balloon distension on pentagastrin-stimulated
      gastric acid secretion and bicarbonate secretion were studied in nine healthy
      subjects and eight duodenal ulcer (DU) patients. The gastric secretions were
      simultaneously measured, using a luminal perfusion and pH/PCO2 measurements. Two
      of the healthy subjects and six of the DU patients were positive for Helicobacter
      pylori. When H. pylori-positive and -negative subjects were compared, basal
      gastric acid and bicarbonate outputs did not differ significantly. In H. pylori
      infected subjects the bicarbonate transport increased by about 70% on
      pentagastrin stimulation. In the H. pylori-negative group pentagastrin had no
      effect on the bicarbonate secretion. Antral distension elicited a 30-35%
      inhibition of pentagastrin-stimulated gastric acid secretion in the group of H.
      pylori-negative subjects, whereas the acid secretory level remained essentially
      unchanged in the positive group. Bicarbonate secretion decreased transiently by
      the distension in the negative subjects, whereas a slight increase was observed
      in the infected group. We conclude that antral distension inhibits pentagastrin
      stimulated gastric acid output in healthy H. pylori-negative subjects. Our
      results strongly suggest that the underlying mechanism is a direct inhibition of
      gastric parietal cell function and not an increased gastric bicarbonate
      secretion. Furthermore, the results indicate that this defective distension
      induced acid inhibition may be correlated to H. pylori infection rather than to
      duodenal ulcer disease.

PMID- 8284639
TI  - Detection of enteroviral RNA by polymerase chain reaction in cerebrospinal fluid
      from patients with aseptic meningitis.
AB  - An assay based on a 2-step (semi-nested) polymerase chain reaction (PCR) was
      developed and evaluated for detection of enterovirus-specific RNA in
      cerebrospinal fluid (CSF) from patients with aseptic meningitis of different
      etiology. The limit of detectability of enteroviral RNA was equivalent to about
      0.25 tissue culture infective doses 50%. In samples, stored at -70 degrees C,
      analyzed without repeated thawing, enteroviral RNA was demonstrable in 21/22 CSF
      specimens from which an enterovirus had been isolated. Enteroviral RNA was shown
      to be degraded during freeze-thawing of the samples. In repeatedly freeze-thawed
      samples from 134 consecutive patients with aseptic meningitis, a lower
      sensitivity (34/48 = 0.71) was observed. In the latest phase of the study,
      comprising 35 consecutive patients, the PCR was performed in CSF stored at -20
      degrees C without thawing. In this material, the PCR yielded positive results in
      19 patients, whereas enteroviruses were isolated from 6 cases only. In the total
      clinical material of 169 patients, 67 (40%) were found positive by PCR, whereas
      an enterovirus was isolated from CSF in 54 (32%) cases. All the 13 isolated
      enterovirus serotypes found in the study were demonstrable by PCR, indicating
      that the assay is broad-reacting within the enterovirus group. The specificity
      appeared to be high, since all of 21 patients with non-enteroviral diagnoses were
      negative by the PCR test, except 1 with an Epstein-Barr virus infection. As
      serological evidence of enteroviral etiology was found in this patient, a dual
      infection seemed probable. This study indicates that enteroviral RNA can be
      detected in CSF by a 2-step PCR in meningitis caused by enterovirus and that the
      technique has the potential to become a screening method for routine diagnosis of
      enteroviral meningitis.

PMID- 8284640
TI  - Seroprevalence of Chlamydia pneumoniae in Taiwan.
AB  - Chlamydia pneumoniae (TWAR) is a relatively newly discovered respiratory tract
      pathogen which was first isolated in Taiwan. In order to describe the
      seroepidemiology of C. pneumoniae in Taiwan, we evaluated 1,085 stored serum
      samples: 904 from patients, 97 from umbilical cord blood samples, and 84 from
      medical personnel at the Veterans General Hospital-Kaohsiung, between January 1
      and April 30, 1991. Antibodies were determined by the use of a
      microimmunofluorescence test using elementary bodies of C. pneumoniae AR-39 as
      antigen. Sera were tested with screening titres of 16 and 512 for immunoglobulin
      G antibody. The antibody prevalence was found to be 23.1% in young children (6
      months to 10 years old), rising to 66.7% in teenagers, and to 96.2% in older age
      groups. These rates were higher than any reported earlier. The progressively
      increasing rates of seropositivity found in older individuals indicated a surge
      of reinfection in these age groups. Only 5 cases were found with micro-IF IgG
      titres equal to or greater than 512. All were asymptomatic according to the
      hospital records. In addition to a high prevalence rate in Taiwan, the data also
      showed high infection rates in teenagers and elderly people.

PMID- 8284641
TI  - Serum antibody responses against shigella lipopolysaccharides and invasion
      plasmid-coded antigens in shigella infected Swedish patients.
AB  - Serum antibody responses to shigella lipopolysaccharide (LPS) and invasion
      plasmid-coded antigens (Ipa) were studied in 74 Swedish patients with culture
      verified bacillary dysentery using class-specific enzyme immunoassay (EIA). Anti
      LPS responses were found in 80% and 79% serum samples, respectively, from S.
      flexneri and S. sonnei infected patients and anti-Ipa responses in 60% and 43%,
      respectively. The mean anti-Ipa IgG antibody titres in S. flexneri infected
      patients remained high for 4-6 months after onset while the anti-LPS IgG antibody
      titres had dropped to normal levels. The specificity of EIA for shigella Ipa was
      90% and for S. dysenteriae, S. flexneri and S. sonnei LPSs it varied between 84%
      and 90%. No close correlations between the anti-LPS and anti-Ipa antibody
      responses were observed indicating that they may be differently regulated. The
      dynamics of the serum antibody responses indicates that an anti-LPS response is a
      good indicator of a recent shigella infection and an anti-Ipa IgG response a good
      indicator of a previous infection.

PMID- 8284642
TI  - Enteroaggregative Escherichia coli may be a new pathogen causing acute and
      persistent diarrhea.
AB  - The role of Hep-2 cell adherent Escherichia coli (EAEC) of localized (EAEC-L),
      diffuse (EAEC-D) and aggregative (EAggEC) phenotype, was investigated in 254
      children aged < or = 48 months seeking treatment for non-bloody diarrhea at an
      outpatient clinic, and in 107 age-matched controls. The stool excretion rates of
      single isolates from patients/controls for the different phenotypes of Hep-2 cell
      adherent E. coli were: EAEC-L, 5.9/2.8%, p = 0.33; EAEC-D, 7.5/12.1%, p = 0.22;
      and EAggEC, 11.8/3.7%, p = 0.03. When patients were categorized by pre-admission
      diarrheal duration > or = 14/< 14 days, the excretion rates were EAEC-L, 0/7.1%;
      EAEC-D, 9.5/7.1%, and EAggEC, 21.4/9.9%, the difference approaching significance
      only for EAggEC (p = 0.06). These findings suggest that EAggEC may be an
      important cause of diarrhea in children, with a predilection to cause prolonged
      disease.

PMID- 8284643
TI  - Endotoxin liberation from Neisseria meningitidis correlates to their ability to
      induce procoagulant and fibrinolytic factors in human monocytes.
AB  - Endotoxin released from different strains of Neisseria meningitidis were studied
      for their ability to induce procoagulant (tissue factor, TF), fibrinolytic
      (plasminogen activator, PA) and antifibrinolytic (plasminogen activator inhibitor
      2, PAI-2) factors in human monocytes. Two meningococcal strains that liberate
      endotoxin (E+; 270+ and 840+) and 2 non-liberating (E-; 270- and 840-) strains
      were used. The endotoxin activity in culture filtrates of these strains was
      monitored with the Limulus amoebocyte lysate (LAL) test. There was a marked
      difference between E+ and E- strains in their ability to liberate endotoxin.
      Suspensions of whole bacteria of all 4 strains induced a significant (14-19-fold)
      increase in monocyte TF expression when present in concentrations > 10(5) CFU/ml.
      At lower concentrations (10(4) CFU/ml), E+ strains were clearly more potent
      stimulators of TF synthesis than E- strains. Culture filtrates of E+ strains were
      up to 10(4)-fold more potent in inducing TF synthesis than filtrates from E-
      strains. This marked difference in inducing potency between E+ and E- strains was
      also observed when monocyte PAI-2 synthesis was examined. The PA expression, on
      the other hand, was suppressed when monocytes were incubated in the presence of
      culture filtrates, especially filtrates from the E+ strains. The increased
      procoagulant and antifibrinolytic activity, together with reduced profibrinolytic
      activity of monocytes, was closely correlated to the amount of endotoxin measured
      in the culture filtrates. These changes may contribute substantially to the
      coagulopathic state seen during systemic meningococcal disease.

PMID- 8284644
TI  - Clinical manifestations and antibody prevalence of Lyme borreliosis and tick
      borne encephalitis in Sweden: a study in five endemic areas close to Stockholm.
AB  - Five populations, including 903 individuals living in 5 different areas close to
      Stockholm, were studied with regard to clinical manifestations and antibody
      prevalence of Lyme borreliosis (LB) and tick-borne encephalitis (TBE). The study
      areas involved 4 groups of islands in the Baltic Sea and 1 island in Lake
      Malaren. Serum samples from each individual were tested for antibody activity to
      Borrelia burgdorferi using a sonicated whole spirochete antigen in an ELISA, and
      to TBE-virus (TBEV) by ELISA and haemagglutination inhibition. A history of LB
      was reported by 1-21% and antibodies to Borrelia burgdorferi were found in 7-29%
      of the participants from the various areas. An increasing seroprevalence with age
      was seen. In sera from 3 different control groups, including 502 individuals
      living in non-endemic areas, antibodies to Borrelia burgdorferi were detected in
      1-2% and from 1 control group including 150 individuals living in the city of
      Stockholm, in 9%. A history of TBE was reported by 0-6% of the individuals and in
      non-immunized individuals seropositivity was seen in 4-22%, depending on the area
      investigated. No antibody activity to TBEV could be detected in sera from persons
      in the 3 control groups living in non-endemic areas, whereas 5% of the controls
      from Stockholm were found to be positive. The prevalence rates of antibodies to
      TBEV in persons vaccinated against TBE were 40%, 53% and 79% after 1, 2 and 3
      injections, respectively.

PMID- 8284645
TI  - Antibody prevalence and clinical manifestations of Lyme borreliosis and tick
      borne encephalitis in Swedish orienteers.
AB  - Antibody prevalence and clinical manifestations of Lyme borreliosis (LB) and tick
      borne encephalitis (TBE) were studied in 362 orienteers from the county of
      Stockholm during a large relay race in October 1990. From all participating
      orienteers, a blood sample was collected and a questionnaire completed. Antibody
      activity to Borrelia burgdorferi was measured using a sonicated whole spirochete
      antigen in an ELISA, and to TBE virus (TBEV) by ELISA and haemagglutination
      inhibition (HI) test. A past history of LB was reported by 6% of the orienteers
      and antibodies to B. burgdorferi were found in 9%. Antibody reactivity to B.
      burgdorferi was found in 1-2% of the sera from 3 different control groups
      comprising 502 persons living in non-endemic areas. The corresponding value was
      9% in sera from a fourth control group consisting of 150 persons living in the
      city of Stockholm. A past history of TBE was reported by 1 orienteer (0.3%) and
      detectable antibodies to TBEV in non-immunized individuals were found in 1%. No
      antibody activity to TBEV could be detected in sera from the control individuals
      living in the 3 non-endemic areas, but in 5% of the controls from Stockholm. In
      this study, there was no indication that frequent or severe manifestations of LB
      or TBE are common among orienteers in Sweden.

PMID- 8284646
TI  - Polymerase chain reaction in the diagnosis of tuberculous meningitis.
AB  - 43 cerebrospinal fluid (CSF) specimens obtained from 20 children with tuberculous
      meningitis (TBM) at varying times during the first month of treatment were
      examined by polymerase chain reaction (PCR) for the presence of M. tuberculosis
      DNA. Overall 27 CSF specimens (63%) from 16 patients (80%) gave > or = 1 positive
      results and positive results were obtained from CSF specimens throughout the
      first 4 weeks of therapy. Nine CSF specimens (21%) gave a doubtful result (only 1
      of duplicate determinations positive) and 7 (16%) a negative result. CSF from
      patients with suspected TBM should be submitted for PCR evaluation and positive
      results may be obtained up to at least 4 weeks after the start of treatment.

PMID- 8284647
TI  - Treatment of non-tuberculous mycobacterial infections in patients without AIDS.
AB  - This report summarizes the results of an 8-year study of the treatment of non
      tuberculous mycobacterial infections and the long-term efficacy of this treatment
      in patients without AIDS. Of 25 patients, aged 10-82 years, 24 had pulmonary
      involvement; in 5 cases as part of disseminated disease. One patient had a renal
      infection only. Predisposing factors were identified in 16 patients. M. avium
      intracellulare and M. malmoense were isolated in 17 and 7 patients, respectively,
      and M. kansasii in 1 patient. Three patients were subjected to lobectomy and 22
      received multiple drug chemotherapy for 18-60 months. Chemotherapy was initially
      effective in 17/22 patients and surgery in 3/3. However, in the end 10 patients
      died of their mycobacterial infection, and 6 are still suffering from chronic
      infection. Only 7 patients appear to be free of disease more than 2 years after
      completing chemotherapy.

PMID- 8284648
TI  - Serum C-reactive protein in the differential diagnosis of acute meningitis.
AB  - The ability of serum C-reactive protein (S-CRP) to differentiate between acute
      bacterial and viral meningitis was evaluated in 235 patients, both children and
      adults. The patients underwent lumbar puncture due to suspected central nervous
      system (CNS) infection. In patients with bacterial meningitis, 7/60 (12%) had S
      CRP concentrations below 50 mg/l. Of these patients, 4 were children below 6
      years of age, all with symptoms of meningitis for less than 12 h before admission
      and 3 adults of whom 1 had symptoms of meningitis for less than 12 h. In patients
      with viral meningitis, 15/146 (10%) had S-CRP concentrations above 50 mg/l. Only
      3 children below 6 years of age with viral meningitis had S-CRP concentration
      above 20 mg/l, but none exceeded 50 mg/l. An S-CRP value above 50 mg/l in
      patients with CSF pleocytosis usually indicates bacterial etiology. However, S
      CRP values above 50 mg/l may occasionally be seen in viral meningitis. In
      children younger than 6 years of age a discriminatory level for S-CRP of 20 mg/l
      can be used to distinguish between bacterial and viral meningitis, but for older
      patients a discriminatory level of 50 mg/l is more appropriate. If the duration
      of the illness is less than 12 h, S-CRP concentrations below the discriminatory
      levels are of limited diagnostic value.

PMID- 8284649
TI  - Comparison of three days' therapy with cefcanel or amoxicillin for the treatment
      of acute uncomplicated urinary tract infection.
AB  - The clinical and bacteriologic efficacy of 3 days of cefcanel daloxate therapy,
      compared with 3 days of amoxicillin for the treatment of acute uncomplicated
      urinary tract infection was compared in a prospective randomized double-blind
      multicentre study. 400 subjects were randomized to receive cefcanel daloxate and
      199 to receive amoxicillin. 166 (77%) of 215 evaluable cefcanel daloxate subjects
      and 72 (77%) of 94 evaluable amoxicillin subjects evidenced bacteriologic
      elimination at short-term follow-up, while in 149 (69%) and 67 (71%),
      respectively, clinical symptoms disappeared. At long-term follow-up, 150 (70%)
      cefcanel daloxate and 65 (69%) amoxicillin subjects evidenced bacteriological
      elimination, while in 150 (70%) and 61 (65%), clinical symptoms disappeared.
      There were no significant differences in outcome between the 2 therapeutic
      regimens. Adverse events were similar in the 2 groups. In additional analyses,
      antimicrobial efficacy diminished significantly with increasing age, pretherapy
      in vitro susceptibility was significantly associated with bacteriological failure
      at the short-term visit, and subjects with low quantitative counts pretherapy had
      clinical outcomes similar to those with quantitative counts > or = 10(5) cfu/ml
      at the short-term outcome. These data suggest that cefcanel daloxate and
      amoxicillin are comparable as regards efficacy and adverse effects for 3-day
      therapy of acute uncomplicated urinary tract infection. The observed cure rates,
      however, are lower than those reported for other agents such as
      trimethoprim/sulfamethoxazole or quinolones for short course therapy.

PMID- 8284650
TI  - Changing pattern of phage group II Staphylococcus aureus infections: from
      community to hospital.
AB  - Changes in Staphylococcus aureus strains of phage group II were evaluated over a
      30-year period. Strains of this group were previously known to be mainly
      community-acquired, to be rather sensitive to antibiotics and to occur in
      infections with better clinical outcome. During the period 1961 to 1990 a total
      of 551, 563 S. aureus strains was characterized according to antibiotic
      resistance, phage type and site of isolation. Clinical information was obtained
      on 16,781 bacteraemia cases. Strains of group II occurred until 1983 with a
      rather constant frequency around 16% of the S. aureus population. Since then, a
      constant increase in frequency has taken place and since 1990 they are the most
      frequently isolated phage pattern (22%). Bacteraemia caused by these strains
      occurs today with the same frequency in hospital and community as strains of
      other phage patterns. Moreover, these strains have changed from being highly
      susceptible, to being more resistant to penicillins and tetracycline than the
      rest of the population. Resistance to methicillin remained low in group II
      strains throughout the period (about 0.2%). Mortality rate and the proportion of
      patients with underlying diseases have been the same in recent years regarding
      group II strains as with other strains. This study indicates that the previous
      distinction between community-acquired and hospital-acquired S. aureus infections
      is no longer valid.

PMID- 8284651
TI  - Pasteurella multocida meningitis in a two-day old neonate.
AB  - A normal full-term baby boy, born by vaginal delivery, became ill on day 2 with
      fever and failure to feed. CSF examination revealed 260 x 10(6)/l leucocytes,
      mainly mononuclears, protein 2 g/l and glucose zero. Pasteurella multocida was
      isolated in pure culture from the baby's CSF, blood and umbilicus and from the
      mother's vagina. The baby was treated with i.v. penicillin for 7 weeks. Progress
      was complicated by mild hydrocephalus, which resolved, and prolonged low grade
      fever. Recovery was complete, without neurological sequelae. This case
      illustrates that P. multocida can infect the vagina where it presents a hazard to
      a newborn infant delivered vaginally. Early diagnosis is critical, intravenous
      high dose penicillin being the treatment of choice.

PMID- 8284652
TI  - Fatal necrotizing fasciitis due to Vibrio damsela.
AB  - A patient who succumbed to fulminant necrotizing fasciitis due to Vibrio damsela
      after injury by a rabbitfish is described. Despite the absence of any known
      underlying illness, he did not respond to appropriate antibiotic therapy and
      radical surgical intervention. This represents the first documented case of
      necrotizing fasciitis due to this organism, and is also the first reported case
      in Southeast Asia inflicted by rabbitfish.

PMID- 8284653
TI  - Meningoencephalitis caused by Toxoplasma gondii diagnosed by isolation from
      cerebrospinal fluid in an HIV-positive patient.
AB  - Toxoplasmosis of the central nervous system is a frequent opportunistic infection
      in AIDS patients, usually presenting as a mass brain lesion detected by
      computerized axial tomography scanning or magnetic resonance imaging. A case of
      diffuse meningoencephalitis with no radiological evidence of brain lesions is
      described. Diagnosis was made by culturing cerebrospinal fluid (CSF) on THP1
      cells where tachyzoites of Toxoplasma gondii were demonstrated after 8 days of
      incubation by both direct observation and immunofluorescence. CSF examination
      with culture should be considered in AIDS patients with neurological signs and
      symptoms but without radiological evidence of cerebral lesions.

PMID- 8284655
TI  - The occurrence of human intestinal parasites in Finland.
AB  - The survey of the occurrence of intestinal parasites presented here covers 726
      hospital patients, 175 healthy adults and 212 children, and 976 healthy Finnish
      holiday-makers prior to their trip abroad. Two faecal samples from each
      individual were examined. Further, 344 children were tested for Enterobius
      vermicularis. The total prevalence of intestinal parasites in the hospital
      patients was 4.2%, and that of pathogenic parasites 2.9%. The prevalence rates in
      healthy subjects were 4.9% and 1.5%, respectively. Three species of pathogenic
      parasites were found: Giardia lamblia, Entamoeba histolytica and Diphyllobothrium
      latum. A test for Enterobius vermicularis was positive in 5.2% of children
      examined.

PMID- 8284654
TI  - First cases of microsporidiosis in Scandinavian patients with AIDS.
AB  - The first 2 cases of infection with Enterocytozoon bieneusi in Denmark and
      Scandinavia are reported. Both patients were women and to the best of our
      knowledge this is the first report of E. bieneusi in female AIDS patients. Both
      had late stage AIDS, and both had complained of intermittent diarrhoea for more
      than 1 year. At the time microsporidiosis was diagnosed, no other pathogens
      causing diarrhoea were found. Immunodeficient patients with chronic unexplained
      diarrhoea should be investigated for intestinal microsporidiosis, especially as
      treatment is now available.

PMID- 8284656
TI  - Animal Sexuality.

PMID- 8284657
TI  - World linguistic diversity.

PMID- 8284659
TI  - Biowarfare wars. Critics ask whether the army can manage the program.

PMID- 8284658
TI  - A war not won.

PMID- 8284660
TI  - Dioxin indictment. A growing body of research links the compound to cancer.

PMID- 8284661
TI  - The toxins of cyanobacteria.

PMID- 8284662
TI  - Health care costs.

PMID- 8284664
TI  - Health care costs.

PMID- 8284663
TI  - Health care costs.

PMID- 8284665
TI  - R&D budget: more wins than losses.

PMID- 8284666
TI  - U.S.-Japan collaboration. Academic biotech deals offer more promise than product.

PMID- 8284667
TI  - Rise and fall of the Y chromosome.

PMID- 8284668
TI  - Unveiling a tuberculosis drug target.

PMID- 8284669
TI  - Ancient tropical climates warm San Francisco gathering.

PMID- 8284670
TI  - A family tree of European bears.

PMID- 8284671
TI  - Nanometer spatial resolution achieved in hard x-ray imaging and Laue diffraction
      experiments.
AB  - Tapered glass capillaries have successfully condensed hard x-ray beams to
      ultrasmall dimensions providing unprecedented spatial resolution for the
      characterization of materials. A spatial resolution of 50 nanometers was obtained
      while imaging a lithographically prepared gold pattern with x-rays in the energy
      range of 5 to 8 kiloelectron volts. This is the highest resolution scanning x-ray
      image made to date with hard x-rays. With a beam 360 nanometers in diameter, Laue
      diffraction was observed from the smallest sample volume ever probed by x-ray
      diffraction, 5 x 10(-3) cubic micrometers.

PMID- 8284672
TI  - Crystal structure of the DNA binding domain of the heat shock transcription
      factor.
AB  - The structure of the DNA binding domain, determined at 1.8 angstrom resolution,
      contains a three-helix bundle that is capped by a four-stranded antiparallel beta
      sheet. This structure is a variant of the helix-turn-helix motif, typified by
      catabolite activator protein. In the heat shock transcription factor, the first
      helix of the motif (alpha 2) has an alpha-helical bulge and a proline-induced
      kink. The angle between the two helices of the motif (alpha 2 and alpha 3) is
      about 20 degrees smaller than the average for canonical helix-turn-helix
      proteins. Nevertheless, the relative positions of the first and third helices of
      the bundle (alpha 1 and alpha 3) are conserved. It is proposed here that the
      first helix of the three-helix bundle be considered a component of the helix-turn
      helix motif.

PMID- 8284673
TI  - inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium
      tuberculosis.
AB  - Isoniazid (isonicotinic acid hydrazide, INH) is one of the most widely used
      antituberculosis drugs, yet its precise target of action on Mycobacterium
      tuberculosis is unknown. A missense mutation within the mycobacterial inhA gene
      was shown to confer resistance to both INH and ethionamide (ETH) in M. smegmatis
      and in M. bovis. The wild-type inhA gene also conferred INH and ETH resistance
      when transferred on a multicopy plasmid vector to M. smegmatis and M. bovis BCG.
      The InhA protein shows significant sequence conservation with the Escherichia
      coli enzyme EnvM, and cell-free assays indicate that it may be involved in
      mycolic acid biosynthesis. These results suggest that InhA is likely a primary
      target of action for INH and ETH.

PMID- 8284674
TI  - Degeneration of a nonrecombining chromosome.
AB  - Comparative studies suggest that sex chromosomes begin as ordinary autosomes that
      happen to carry a major sex determining locus. Over evolutionary time the Y
      chromosome is selected to stop recombining with the X chromosome, perhaps in
      response to accumulation of alleles beneficial to the heterogametic but harmful
      to the homogametic sex. Population genetic theory predicts that a nonrecombining
      Y chromosome should degenerate. Here this prediction is tested by application of
      specific selection pressures to Drosophila melanogaster populations. Results
      demonstrate the decay of a nonrecombining, nascent Y chromosome and the capacity
      for recombination to ameliorate such decay.

PMID- 8284675
TI  - Innervation of the heart and its central medullary origin defined by viral
      tracing.
AB  - The vagus nerve exerts a profound influence on the heart, regulating the heart
      rate and rhythm. An extensive vagal innervation of the cardiac ventricles and the
      central origin and extent of this innervation was demonstrated by transynaptic
      transport of pseudorabies virus with a virulent and two attenuated pseudorabies
      viral strains. The neurons that innervate the ventricles are numerous, and their
      distribution within the nucleus ambiguus and dorsal motor nucleus of the vagus is
      similar to that of neurons innervating other cardiac targets, such as the sino
      atrial node. These data provide a neuroanatomical correlate to the physiological
      influence of the vagus nerve on ventricular function.

PMID- 8284676
TI  - Phase shifting of the circadian clock by induction of the Drosophila period
      protein.
AB  - Virtually all organisms manifest circadian (24-hour) rhythms, governed by an ill
      defined endogenous pacemaker or clock. Several lines of evidence suggest that the
      Drosophila melanogaster period gene product PER is a clock component. If PER were
      central to the time-keeping mechanism, a transient increase in its concentration
      would cause a stable shift in the phase of the clock. Therefore, transgenic flies
      bearing a heat-inducible copy of PER were subjected to temperature pulses. This
      treatment caused long-lasting phase shifts in the locomotor activity circadian
      rhythm, a result that supports the contention that PER is a bona fide clock
      component.

PMID- 8284677
TI  - [Management of the patient with craniocerebral injuries at the accident site and
      clinic admission].
AB  - Between January 1991 and December 1992, there were 686 rescue operations
      involving patients with craniocerebral trauma in the catchment area of Ulm. There
      were 376 patients who had to be graded as seriously injured according to the NACA
      classification. In 178 cases there was a severe craniocerebral trauma, and 131 of
      these patients were admitted to the traumatology department of the University of
      Ulm. The pattern of injuries was analysed; multiple injuries were found in 63
      patients, with injuries to the extremities and the thorax being most-frequent.
      The primary preclinical treatment for patients with craniocerebral trauma is
      demonstrated; the indications for intubation and artificial respiration are
      discussed, and also the selection of drugs. Diagnostic procedures and immediate
      treatment must initially be directed at securing vital functions. Treatment of
      life-threatening haemorrhage has priority over neurosurgical diagnosis and
      therapy. The urgent indications for neurosurgical intervention are: space
      occupying intracranial bleeding, open craniocerebral traumas, and space-occupying
      depressed fractures.

PMID- 8284678
TI  - [Computerized tomography and craniocerebral trauma].
AB  - Computed tomography (CT) is now the standard neuroradiological examination for
      patients with major head injuries, although conventional X-ray of the skull
      should not be neglected. Whereas the latter only shows such skull pathology as
      fractures or intracranial air following a basal fracture, CT clearly visualizes
      intracranial pathology. It allows differentiation between haematoma and
      contusion, between localized oedema and generalized brain swelling; CT is
      therefore indicated in every patient with disturbed consciousness, focal
      neurological signs, and/or secondary clinical impairment, and also in all drunken
      patients with head injury. In a patient with impaired consciousness and focal
      neurological deficit the probability of a pathologic CT is 85%. An extracerebral
      haematoma is often present, which needs urgent evacuation. A modern, non
      expensive communications system using a standard telephone line enables hospitals
      without a neurosurgical unit to send CT pictures that are difficult to interpret
      to a neurosurgeon and to discuss them on-line by telephone. This system has now
      been in operation for over 2 years and has improved the care of patients with
      head injury in our region. It is highly efficient and reliable and improves
      cooperation between distant hospitals. It also helps to avoid unnecessary
      transfers, which are not only expensive but may even harm a critically ill
      patient.

PMID- 8284680
TI  - [Surgical indications in space-occupying contusion hemorrhage].
AB  - Traumatic intracerebral haematomas are a common neurosurgical emergency. The role
      of surgical removal is controversial. The diagnosis and treatment of life
      threatening thoracic or abdominal haemorrhage is more urgent than are measures
      undertaken by the neurosurgeon. In the present paper we report on 318 patients
      with severe head injury. In 161 cases (38 female, 123 male) CT investigation
      showed a a resulting from contusion. About a third of each group of patients,
      both with and without contusion-induced haematomas, were 21-30 years old. The
      mortality rate was 18.6%. Multiple contusion haematomas occurred in 36%, and
      solitary ones in 64%. The diagnostic investigations showed contusion haematomas
      in isolation only in 10.6% of patients. All others had additional injuries:
      epidural haematomas in 24 cases, subdural haematomas in 29, depressed fractures
      of the skull in 6, and traumatic subarachnoid haemorrhage in 37. Only 10 patients
      underwent operative removal of their contusion haematomas by trepanation and 2
      others by stereotactic puncture.

PMID- 8284679
TI  - [Treatment measures in traumatic extracerebral hemorrhage. Management of epi
      /subdural hemorrhage and prognosis].
AB  - Surgical therapy for intracranial extracerebral haemorrhages is one of the oldest
      surgical techniques. The low mortality and morbidity in recent years have come
      about through of the emergency service, modern neurosurgical techniques,
      widespread use of the CT scanner, and adequate intensive care. The treatment
      target in the case of head injuries is to provide the optimal milieu for recovery
      from the primary injury and to prevent secondary damage to the brain. Acute
      subdural haematomas (SDH) are the most frequent traumatic lesion. The outcome is
      related more to the degree of associated brain damage than to the subdural clot
      itself. Once the stability of vital functions has been assured to prevent
      intracranial hypertension, a craniotomy to remove the haematoma must follow
      immediately. Intracranial pressure (ICP) monitoring is mandatory after evacuation
      of the clot. Results of the preliminary analysis of the Traumatic Coma Data Bank
      (TCDB) show a 50% mortality rate after operative treatment of subdural
      haematomas. Chronic SDH is a different entity in terms of manifestations, time
      course and outcome. Twist drill evacuation of the fluid (= chronic haematoma) in
      local anaesthesia is now accepted as the treatment of choice. An extradural
      haematoma is a potentially lethal lesion with a mortality rate of 5%. Emergency
      surgical intervention is appropriate before neurological signs appear.

PMID- 8284681
TI  - [Special aspects in diagnosis and treatment of open craniocerebral injuries
      including basilar skull fractures].
AB  - The possibility of CSF leakage means that open head injuries and skull base
      fractures are serious and sometimes dangerous. An operation should be considered
      in cases of open depressed skull fractures with or without space-occupying
      haematoma, compound fractures of the rhinobasis and orbita, dislocated fractures
      of the dorsal wall of the frontal sinus, CSF leakage for longer than 1 week, and
      posttraumatic intracranial infection. Operative and posttraumatic intracranial
      infection is also potentially dangerous. The operative approach depends on the
      type and localization of the fracture. The transsphenoidal and frontoorbital
      approaches are less traumatic, but offer only limited visibility. The
      transfrontal intradural approach offers by far the best view of the frontobasis
      and is therefore indicated in most cases.

PMID- 8284682
TI  - [Early and late complications of craniocerebral trauma. Chronic subdural
      hematoma/hygroma, carotid-cavernous sinus fistula, abscess formation, meningitis
      and hydrocephalus].
AB  - A group of 318 patients suffering from severe head injury, 51 of whom died of
      their (head) injury, is reviewed. A small contusional cerebral haemorrhage had
      occurred in 50.6%, and 30% had had basal skull fractures. In the entire group,
      2.8% developed posttraumatic hydrocephalus. Shunt implantation was necessary
      between the 11th and 123rd posttraumatic days (mean 52nd). All patients with
      inflammatory problems, e.g. meningitis or intracranial abscess, developed
      posttraumatic hydrocephalus. In 10 of the 12 patients with hygromas, an operative
      procedure with bur hole trepanation was necessary. Half of the patients with
      hygromas were polytraumatized but only 25.85% of the entire group. Two patients
      in the group and a further 49 patients with chronic subdural haematomas were
      operated on by a bur hole trepanation and appropriate drainage for several days.
      In 2 cases the development of the chronic subdural haematoma had been documented
      by CAI. All patients with frontobasal skull fractures were operated on by a
      transethmoidal approach only the 1st day. Only 2 of the laterobasal skull
      fractures needed an operation. One of these caused was by a pneumocephalus. In
      0.9% of the patients an intracranial abscess was present; these all had a basal
      skull fracture, 1 after gunshot injury. Among the patients with basal skull
      fractures 3.1% developed carotid artery-cavernous sinus fistula. One of these
      three fistulas has been documented as yielding to spontaneous closure. After
      reangiography for balloon occlusion an aneurysm was found. Following primary
      operation, 2.5% of patients required revision operation because of renewed
      bleeding. The posttraumatic treatment of the complications is discussed.

PMID- 8284683
TI  - [Pediatric craniocerebral trauma. Special characteristics, therapy and
      prognosis].
AB  - The mortality rate after traumatic brain injury in children ranges between 2.5%
      and 21%. Standardized diagnostic procedures and therapeutic strategies for the
      management of traumatic brain damage are presented in this article. Children with
      traumatic cerebral lesions have a better clinical outcome than head-injured
      adults. Optimized medical management and intensive rehabilitation may help to
      reduce the frequency of mental retardation and physical disability following such
      injuries in children.

PMID- 8284684
TI  - [Expert assessment of craniocerebral trauma].
AB  - The officially appointed external expert needs a precise documentation of the
      initial clinical findings and the findings at follow-up of the patient with
      craniocerebral trauma. The next step in preparation of the expert report consists
      in a pathophysiological and a neurological examination, including CT scan and EEG
      repeated at intervals; a stable condition can be expected after 1-2 years. In the
      case of reversible closed head syndrome (brain concussion) the expert should
      certify a disability for about 6 months; a degree of 20% for over 3 months should
      not be certified unless there are massive vegetative signs and symptoms.
      Persisting damage should only be recognized if a substantial brain lesion is
      present. In cases of cerebral compression or open skull fracture with manifest
      damage to the substance of the brain the duration of unconsciousness must be
      taken into account. For children and young people up to 10 days' unconsciousness
      is not taken to imply later disability; after 10-20 days' unconsciousness such
      young people are considered fit for work or school to a qualified extent; a
      persistent defect must be expected to follow unconsciousness lasting over 20
      days. Adults who are unconscious for up to 5 days can be expected to make a
      complete recovery, while a longer duration of coma and more advanced age are
      associated with a worse outcome. The degree of functional impairment is thus
      important in the expert's decision on the level of disability. A flow chart is
      presented for guidance in the preparation of expert reports.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8284685
TI  - Interleukin-2: Advances in Clinical Research and Treatment. Proceedings of a
      meeting. Colorado Springs, Colorado, June 24-27, 1993.

PMID- 8284686
TI  - Combination biologic therapy with interleukin-2 and interferon-alfa in the
      outpatient treatment of metastatic renal cell carcinoma.

PMID- 8284687
TI  - A progress report on the outpatient treatment of patients with advanced renal
      cell carcinoma using subcutaneous recombinant interleukin-2.

PMID- 8284688
TI  - European studies of interleukin-2 in metastatic renal cell carcinoma.

PMID- 8284689
TI  - Low-dose recombinant interleukin-2 therapy: rationale and potential clinical
      applications.
AB  - Interleukin-2 is a lymphocytotrophic hormone that plays a critical role in the
      host's normal immune response. Deficiencies in the production of IL-2 are likely
      to be important in the pathogenesis of certain infectious and malignant diseases.
      A better understanding of IL-2 and its potential applications in the treatment of
      human disease will come about with continued efforts in at least two areas.
      First, we must continue to characterize IL-2 receptor expression on the cells
      that normally use IL-2, in an attempt to fully elucidate their functional
      responsiveness to this hormone in vitro and their physiologic role in vivo.
      Second, we should proceed with clinical trials that use rIL-2 in an effort to
      assess cellular and humoral responses in vivo, and to learn more about the
      ability of rIL-2 to provide additional defense against persistent infection or
      malignancy in both immunocompromised and cancer patients.

PMID- 8284690
TI  - The role of recombinant interleukin-2 in therapy for hematologic malignancies.

PMID- 8284691
TI  - Interleukin-2 therapy after autologous bone marrow transplantation for
      hematologic malignancies.

PMID- 8284693
TI  - Interleukin-2 antitumor and effector cell responses.
AB  - Based on the above considerations, there are a number of implications for the
      clinical development of rIL-2 that depend on the putative effector cell. If the
      effector cell responsible for rIL-2-mediated antitumor effects is the LAK cell,
      effective treatment regimens will likely continue to require extremely high doses
      of rIL-2. Based on preclinical models, one would also predict that LAK cell
      mediated tumor killing against nonimmunogenic tumors would be most effective in
      low tumor burden states and could only be demonstrated clinically in large-scale,
      randomized, adjuvant trials. On the other hand, some weakly immunogenic tumors
      might be susceptible to CTL-mediated killing even when disease was further
      advanced. The antitumor activity of rIL-2 in patients with large tumors suggests
      that this might be the case for some patients with RCC. Treatment approaches that
      result in the generation of relevant effector cell populations would be expected
      to markedly enhance CTL-dependent rIL-2 antitumor activity. However, unless
      antigenic heterogeneity was minimal, multiple tumor antigen-specific T-cell
      populations would have to be generated for responses to be complete and durable.

PMID- 8284692
TI  - Treatment with pentoxifylline and ciprofloxacin reduces the toxicity of high-dose
      interleukin-2 and lymphokine-activated killer cells.

PMID- 8284694
TI  - Women, development and health. Introduction.

PMID- 8284695
TI  - Health-seeking behavior of Rwandan women.
AB  - The responses of Rwandan women in a highland region to their own and their
      children's illness episodes are examined. Over 85% of diarrhea cases from monthly
      morbidity recalls were treated by health-center visits, use of Western medicine,
      or no treatment. Factors such as the age of the child at the time of the illness,
      previous child death in the household, and the women's control of various
      categories of household expenditures exert some influence on health-seeking
      behavior, according to results of cross-tabulations. Women at the highest
      altitudes tend to respond less actively to children's diarrhea, possibly because
      of the relative difficulty of their journey to the health center. Recommendations
      are offered for policy and further study.

PMID- 8284696
TI  - Children's nutritional status in female-headed households in the Dominican
      Republic.
AB  - A national representative household survey of food consumption, income, and
      expenditure was conducted in the Dominican Republic in 1986 by Tufts University
      School of Nutrition in cooperation with USAID Office of Nutrition [1: Rogers B.
      L. and Swindale A. Determinants of Food Consumption in the Dominican Republic.
      USAID/S & T/Nutrition, Washington, DC, 1988]. Out of 1440 families surveyed 706
      had children under 6 years of age. Anthropometric indicators of height and weight
      were collected for all 1251 children in the sample in a follow-up study conducted
      from December 1986 to January 1987 by Tufts with USAID/Santo Domingo Mission
      funding. Anthropometric measurements were converted to standard deviation scores
      using NCHS standards; nutritional status was thus measured by height-for-age
      (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ). Earnings in families
      with children having males as heads-of-household were roughly one-third greater
      than in those with females as household head; total income was also greater in
      these families, though not significantly. More calories and protein per adult
      equivalent were available in male-headed families as well. In spite of this
      superior economic and dietary situation, there was a trend throughout the entire
      sample for children of female-headed households to be taller and heavier for
      their age than those of two parent homes; all three anthropometric measures
      showed differences in the same direction. In the lowest expenditure quartile, WAZ
      and WHZ were significantly greater for children in female-headed households than
      their counterparts in male-headed households (WAZ: P = 0.01, WHZ: P =
      0.00).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284697
TI  - Influences of mothers' and fathers' income on children's nutritional status in
      Guatemala.
AB  - The relative effects of fathers' and mothers' income on children's nutritional
      status were examined with a sample of 294 peri-urban Guatemalan children aged 8
      47 months. Whether or not incomes tended to be pooled, and the relation of income
      earning to decision-making about purchases were examined. Four measures of income
      were constructed for both mother and father: total income, contribution to the
      household food budget, percentage of her/his income contributed to the household
      food budget, and a percentage of total family income earned by that person. In
      the majority of households, women did not report pooling their incomes. Women who
      earned a higher proportion of the family income had significantly more control
      over decision-making in all areas except food purchases, which were already
      primarily women's decisions. Relationships of income measures with children's
      nutritional status were examined with multiple linear regression analyses
      controlling for potentially confounding variables. For mothers, the percentage of
      the total family income they earned was most highly associated with children's
      nutritional status, suggesting that income control by mothers may have benefits
      for children. For fathers, the percentage of their income they contributed to the
      household food budget was most highly associated with children's nutritional
      status, suggesting that father investment or attitude toward children has
      important benefits for children.

PMID- 8284698
TI  - Agricultural productivity, seasonality and gender bias in rural nutrition:
      empirical evidence from south India.
AB  - This paper analyzes changes in the nutrients intake, intra-household allocation
      and gender bias due to changes in agricultural productivity among four groups of
      rural households over six different seasons. The study utilizes household survey
      data collected from a village in Tamil Nadu, India. While the results are
      consistent with earlier findings that seasonality influences variation in the
      intake of nutrients, it is shown that subsistence agricultural households recover
      faster from poor crop yields than market oriented agricultural households in
      terms of nutrient intake. Agricultural labour households consumed lowest
      quantities of energy and protein in all the seasons with the highest degree of
      gender bias. The gender bias is more in terms of protein intake compared to
      energy intake for all the households. The non-agricultural households are least
      affected due to variability in crop yields and seasonality. While nutritional
      intake of the rural households is positively correlated with crop yields, the
      variations in yields worsen the gender bias. It is argued that reducing
      dependency of rural households on agriculture may reduce malnutrition and the
      gender bias associated with it.

PMID- 8284699
TI  - Midwives in the Mexican health system.
AB  - The health care system in Mexico was built upon a western model in which curative
      rather than preventive medicine is emphasized. However, the incorporation of
      indigenous midwives into maternal and child care and family planning programs by
      several public health agencies is an exception to the governmental health
      policies. An analysis of midwife preferences among rural women indicates that
      primarily poor illiterate women with children, living in remote areas with
      difficult access, rely on midwives. The continued reliance on midwives by this
      sector of the population makes the government programs most important. These
      programs are a unique case in which the incorporation of traditional
      practitioners in the modern health system has occurred. However, in order to
      implement programs that have the capability to offer rural women the benefits of
      both health systems, the incorporation of the traditional midwives requires not
      only the upgrading of their skills in modern antiseptic techniques, but the
      recognition of the contributions of traditional health practices, and the
      research of elements and practices to foster its understanding.

PMID- 8284700
TI  - The education and contribution of women health care professionals in Saudi
      Arabia: the case of nursing.
AB  - "Women constitute the key resource for attaining the goal of health for all by
      the year 2000," maintains a report by The World Health Organization. Achieving
      this goal requires massive efforts including (1) the training of women health
      care professionals; and (2) the nonformal health education of women, the primary
      health care providers to their families and communities. This paper focuses on
      the first area, specifically on the education of women nurses in a Third World
      country, Saudi Arabia, where traditional attitudes persist against intermingling
      of the genders and the treatment of women by men. It examines the progress and
      problems encountered in recruiting Saudi women for nursing education and
      practice; describes the evolution of nursing education programs; and analyzes the
      obstacles to women's participation in these programs and in the nursing
      profession. The paper concludes with recommendations to address the problem,
      increase women's participation, and contribute to that country's health
      development. The paper is based upon primary and secondary data, including
      official statistics; personal interviews with Saudi women health professionals
      and students; the memoirs of a leading Saudi woman nurse and educator, the
      author's personal observations and experiences with the health care system during
      four years of residence in Saudi Arabia, and available literature on the subject.

PMID- 8284701
TI  - Rural origin as a risk factor for maternal and child health in periurban Bolivia.
AB  - Rapid migration in Latin America is settling rural women and their families next
      to those of urban origin in sprawling urban settings. Those born and reared in
      rural areas bring with them knowledge and skills learned and adapted to rural
      areas; those same skills may be maladaptive in urban areas. Hypothesized is that
      urban women of rural origin are more likely to have poorer health outcomes for
      themselves and their children than lifelong urban counterparts. Identification of
      specific risk factors affecting child and/or maternal health status in peri-urban
      barrios can assist health workers to target limited resources to those least
      likely to access available services.

PMID- 8284702
TI  - The health status of women in Oaxaca: determinants and consequences.
AB  - Survey data from a sample of 575 women from the city of Oaxaca de Juarez, Mexico,
      are analyzed to ascertain the effect of the receipt of job-related benefits,
      including health benefits, on the self-reported health status of women, their
      rating of the health of the members of their household, and their satisfaction
      with the health of the members of their household. Health status depends on the
      woman's age, her socioeconomic status, and the number of children she has borne.
      Her rating of the health of the members of her household is related to her age,
      her socioeconomic status, and her rating of her own health. Satisfaction with the
      physical health of the members of the household is a function her health, her
      rating of the health of her household, her age, her socioeconomic status and the
      number of children she has borne. The overall conclusion is that, in this study,
      it is socioeconomic and demographic factors that are important in determining the
      woman's health status, rather than the receipt of job-related benefits. That she
      reports good health is an important factor in her view of her family's health and
      her satisfaction with her own health and that of her family.

PMID- 8284703
TI  - Prenatal diagnosis and sex selection in 19 nations.
AB  - As part of a study of ethics and human genetics in 19 nations, we surveyed
      attitudes of 71 medical geneticists in 4 developing nations (Brazil, Greece,
      India and Turkey), and 611 geneticists in 15 developed nations, using anonymous
      questionnaires. Overall, 52% in India, 30% in Brazil, 29% in Greece, and 20% in
      Turkey would perform prenatal diagnosis to select a male fetus for a couple with
      4 daughters and no sons. Sex selection is the major use of prenatal diagnosis in
      India. The majority in the U.S.A. (62%) and Hungary (60%) would also do sex
      selection or refer. We discuss possible means of preventing sex selection while
      avoiding medical paternalism and promoting the autonomy of women.

PMID- 8284704
TI  - Family composition strategies in rural north India.
AB  - Recent evidence on child mortality and fertility trends in the community known as
      Karimpur in the north Indian state of Uttar Pradesh presents a troubling puzzle:
      the female children of the poor are now dying at a much more rapid rate than
      their brothers. In this community, sex-specific child mortality is not new. What
      is new is the increasing female bias in child mortality among the poor. My
      contention is that this trend can only be understood in the larger context of
      family composition strategies, strategies which have changed due to the socio
      economic changes wrought by the green revolution and other development programs
      of the past 25 years. Moreover, mortality cannot be understood without also
      considering fertility behavior and the overall shape of the resulting families.
      My hypothesis is that the Karimpur poor are using high fertility and sex-specific
      child mortality to maximize the number of surviving males in attempting to insure
      family welfare.

PMID- 8284705
TI  - When more means less: assessing the impact of dairy 'development' on the lives
      and health of women in rural Rajasthan (India).
AB  - Following upon the proclaimed success of cooperative dairy schemes in other parts
      of India (Operation Flood based on the Amul model), the Rajasthan government is
      attempting a similar scheme. A key theme of the project is to bring women into
      the mainstream of dairy development in order to improve their economic,
      nutritional, and social status. For this purpose a special program was initiated
      to train poor rural women in 'dairy camps' on how to care for their milch
      animals. Successful completion of such 'camp' training then qualifies the woman
      for a loan to buy an animal in her name. It is hoped that a part of the milk
      obtained will go to the village dairy cooperative. The major aims of this program
      are to: remove milch animals from the cities; encourage production of more milk
      for the cooperative dairies; encourage modern techniques of animal care; put
      control of the income from milk-selling in the hands of the women who care for
      the animals by permitting them to own the animals and hence contribute to their
      'independence' and 'development;' and to encourage self-sufficiency for the
      weaker sections by providing loans to the poor. Data for this paper were
      collected during fieldwork in a village in Alwar District, Rajasthan and
      specifically from observation and participation in the two-week dairy 'camp'
      there. Eighteen women were selected on poverty criteria to participate in the
      program. The general situation of these women is analyzed within the context of a
      critical discussion of the dairy movement in India, in general, and the intended
      effects on the lives of the village women, in particular, with special attention
      to the impact on their workload, nutritional intake and, ultimately, overall
      health. Concluding remarks are addressed to the broad issues of government
      development programs and why more of the same type of development strategies
      persist in the face of often-repeated failures.

PMID- 8284706
TI  - Child and maternal health and international economic policies.
AB  - The following article suggests that the current economic crisis in the Dominican
      Republic could have serious consequences for the health of women and children.
      Health status will be affected both indirectly and directly by the crisis: that
      indirect effect can be seen in changes in dietary patterns, increased nutritional
      risk, increased incidence of infectious disease, and in time, increased mortality
      among women and children. The direct effect can be seen in higher unemployment,
      reduced wages, increased prices of basic commodities, and reduced government
      support for public health care delivery systems. Examples are drawn from
      observations in public health postpartum wards.

PMID- 8284707
TI  - AIDS action-research with women in Kinshasa, Zaire.
AB  - AIDS has assumed epidemic proportions in Central Africa. Knowledge of culturally
      constructed gender relations and sexual meanings is crucial to developing
      prevention strategies and reducing the impact of AIDS. CONNAISSIDA, a
      transdisciplinary medical anthropology research project, developed culturally
      appropriate community-based empowerment workshops. These used cognitive,
      emotional and social stimulants to provoke critical reflection and action.
      Collaborative relationships developed in workshops were used to study sexual
      relations in many contexts. Significant changes in knowledge and action were
      observed. Nevertheless, economic necessity and inequality limited the ability of
      many women to avoid sexual risk. Economic crisis, structural adjustment and debt
      reimbursement policies have exacerbated poverty, particularly among women.
      Linking macrolevel political economy to microlevel sociocultural analysis shows
      how strategies adopted for survival contribute to sexual risk. Therefore broader
      socioeconomic changes that reduce poverty and gender subordination are necessary
      to control the HIV/AIDS epidemic. Findings from Zaire are widely applicable in
      the region.

PMID- 8284708
TI  - Hormonal therapy for metastatic prostate cancer: issues of timing and total
      androgen ablation.
AB  - This review summarize results of hormonal management in patients with metastatic
      prostate cancer in terms of both timing and amount of androgen blockade. The
      standard of delayed hormonal therapy resulted from data of the Veterans
      Administration Cooperative Urologic Research Group showing high toxicity in
      patients treated with estrogen therapy. Reanalysis of those data using cancer
      specific deaths showed improved cancer-specific survival with early hormonal
      therapy. A large and growing body of clinical data also suggests a superior
      benefit to early hormonal therapy. The concept of total androgen (adrenal and
      testicular) ablation was supported by reports that show a survival advantage
      using a combined blockade over luteinizing hormone-releasing hormone agonist
      alone. A National Cancer Institute study showed particularly impressive disease
      free and overall survival in a subset of patients with low volume disease and
      good performance status. However, caution should be exercise in view of differing
      Canadian and European data. This review provides guidelines for treatment, but
      ultimately the timing and amount of androgen deprivation must be tailored to the
      individual patient. Ongoing and future prospective studies hold the promise of
      answers to these difficult and unresolved questions.

PMID- 8284709
TI  - Suicide in Alabama, 1980 to 1989.
AB  - Trends of US suicide rates show great variations among demographic groups over
      time. Although more attention has been directed to the increasing suicide rate
      among adolescents, persons aged 65 years and older continue to commit suicide at
      a higher rate than for any other age group. To examine the recent trend of
      suicide rates and compare the suicide pattern with that at the national level, we
      conducted a study using suicide data in Alabama from 1980 to 1989. For all age
      groups in Alabama in the 1980s, male suicide rates exceeded female rates. Of the
      four major race-sex groups, nonwhite females are an especially low-risk group,
      experiencing a rate of about 1.5/100,000 at all ages. There have been remarkable
      increases in suicide rates in the 1980s for males, especially for nonwhite males
      in Alabama. The results suggest that high-risk groups to be targeted for
      interventions are men over age 45 (especially white men over age 65), and
      divorced and widowed men and women.

PMID- 8284710
TI  - Therapeutic blood monitoring of tricyclic antidepressants.

PMID- 8284711
TI  - Small fenestra stapedotomy for management of progressive conductive deafness.
AB  - Progressive conductive deafness may be caused by otosclerosis, a bone fixation of
      the stapes that causes reduced transmission of sound from the eardrum to the
      inner ear. Since the late 1950s, stapes surgery has been considered the treatment
      of choice for alleviating hearing loss due to otosclerosis. Over the past 20
      years, there has been a decline in the number of stapes operations done. As a
      result, there are concerns regarding results of the stapes surgery done today
      compared with the results of such surgery when it was done more frequently. In
      this paper, I retrospectively review 603 stapes operations that I did at the
      Farrior Ear Clinic between 1981 and 1991. There were 484 primary stapes
      operations. Hearing results using the small fenestra technique showed closure of
      the air-bone gap to 10 dB or less in 96% of cases. During the same period, 119
      revision operations were also done. The surgical technique, operative findings,
      and hearing results are presented. In both primary and revision stapes surgery,
      the hearing results of this series are compatible with the results of earlier,
      larger series. My findings show that stapes surgery is still the treatment of
      choice for hearing loss due to otosclerosis.

PMID- 8284712
TI  - Incidence of inguinal hernias diagnosed during laparoscopy.
AB  - This prospective study was done to identify the incidence of asymptomatic hernias
      diagnosed during laparoscopic surgery. Previously unidentified inguinal hernias
      were discovered in 13 of 100 consecutive patients undergoing laparoscopic
      procedures (13%). Nine of the patients were male, four were female. The average
      age was 43.3 years. Four defects were direct and nine were indirect (patent
      processus vaginalis). Eleven defects were small (< 3 cm) but two were large (> 3
      cm). All four direct defects occurred in male patients. We conclude that
      asymptomatic defects are surprisingly common in our surgical population (13%) and
      that laparoscopic examination of the pelvis is a sensitive technique for
      identifying these defects. To date, no patient with laparoscopically diagnosed
      hernia has had symptoms or complications related to the hernia. We recommend that
      the surgeon should note in the medical record the presence of a defect, but not
      proceed with prophylactic repair of asymptomatic defects.

PMID- 8284713
TI  - Bartholin's duct abscess and cyst: a case-control study.
AB  - Little is known about the epidemiology of Bartholin's duct abscess and cyst. We
      did an emergency department-based case-control study to examine demographic risk
      factors for this condition. We found that risk varied by age. After adjustment
      for pregnancy status, the relative odds (odds ratio [OR]) of occurrence of
      Bartholin's duct abscess for women 20 to 29 years old, compared to women younger
      than 20 years, was 2.3. The association was weaker among women in their 30s and
      40s (OR = 1.4 and 1.1, respectively). The majority of patients were Hispanic
      whites (66% of cases and 79% of control subjects). Risk of Bartholin's duct
      abscess was greater among non-Hispanic white women (OR = 1.9) and black women (OR
      = 2.4). At lowest risk of this condition were women with high parity (> or = 4)
      or high gravidity (> or = 5). These findings suggest that the risk factor profile
      of this condition is similar to that of most sexually transmitted diseases. The
      advisability of presumptive antibiotic treatment of these patients and
      examination and treatment of their sexual partners should be considered.

PMID- 8284714
TI  - Niacin-induced hepatotoxicity: unusual presentations.
AB  - We report four cases of niacin-induced hepatotoxicity. All four patients were
      using sustained-release niacin preparations. When they stopped taking niacin,
      symptoms and laboratory abnormalities resolved. Two of the patients had focal
      fatty infiltration of the liver on imaging studies, a presentation of niacin
      hepatotoxicity not previously described. One patient had a coagulopathy even
      though aminotransferase levels were only mildly elevated. We recommend that
      patients using sustained-release preparations of niacin have periodic monitoring
      of liver enzymes and that the preparation be discontinued if any abnormalities
      develop.

PMID- 8284715
TI  - Arteriographic incidence of coronary artery disease in black men with chest pain.
AB  - To determine the incidence of arteriographically proven coronary artery disease
      in black men evaluated for chest pain, we retrospectively reviewed the charts of
      208 black men, aged 20 to 60, who had coronary arteriography at the Medical
      Center of Central Georgia (MCCG) from 1985 through January 1990. Age, type of
      chest pain, and risk factors commonly accepted as associated with coronary
      disease (hypertension, family history, left ventricular hypertrophy, diabetes,
      smoking, and hypercholesterolemia) were identified for each patient. Patients
      were categorized by previous evidence of coronary disease: 145 were studied to
      evaluate suspected disease and 63 to evaluate previously proven (prior
      catheterization) or presumptive (prior myocardial infarction) disease. Chest pain
      groups (typical and atypical angina) were analyzed by Pearson chi-square goodness
      of fit using the Diamond and Forrester age and chest pain tables as a model. Risk
      factors were analyzed using a maximum likelihood chi-square test. Coronary artery
      disease was common in the study group (48.6% of all patients) but significantly
      less than predicted by the Diamond and Forrester tables. Risk factors were highly
      prevalent, but only age and smoking were associated with catheterization-proven
      coronary artery disease in this group. We conclude that coronary artery disease
      is common in black men evaluated for chest pain but less frequent than would be
      expected from comparison with findings in white men presenting similar clinical
      features. Risk factors other than age and smoking were not associated with
      increased incidence of disease. A prospective study is needed to delineate a more
      effective means of evaluating black male patients with chest pain.

PMID- 8284716
TI  - Impact of immunization against Haemophilus influenzae type b (HIB) on the
      incidence of HIB meningitis treated at Arkansas Children's Hospital.
AB  - The newly available Haemophilus influenzae type b (HIB) protein conjugate
      vaccines are efficacious among study populations in which a high proportion of
      infants and children are vaccinated. In this retrospective study, we show the
      impact of the availability of HIB conjugate vaccines on the incidence of HIB
      meningitis at Arkansas Children's Hospital (ACH) in Little Rock. The Arkansas
      State Health Department estimates that only 43% of children in the state younger
      than 2 years of age have received the appropriate vaccinations. From 1985 through
      1987, 27.3 +/- 4 HIB meningitis cases per year were treated at ACH. Although an
      HIB conjugate vaccine was licensed for 18-month-old children in December 1987,
      the incidence of HIB meningitis treated at ACH did not decrease significantly;
      there were 19.0 +/- 2 cases per year from 1988 through 1990. In December 1990, an
      HIB conjugate vaccine was licensed for use in infants beginning at 2 months of
      age. From that time through August 1992, there were five cases of HIB meningitis
      treated at ACH, representing a significant decrease over previous years. Four of
      these cases occurred in unimmunized infants younger than 6 months of age. The
      availability of HIB conjugate vaccines for infants has resulted in a dramatic
      decrease in the number of cases of HIB meningitis treated at ACH, despite a
      relatively low proportion of infants and children who are receiving vaccination.

PMID- 8284717
TI  - Serum potassium concentrations in trauma patients.
AB  - Hypokalemia occurs in 50% to 68% of trauma patients. To investigate the
      pathophysiology of these changes in serum potassium, we prospectively studied 133
      trauma patients. Among the patients who had hypokalemia, the serum potassium
      usually decreased within 1 hour of trauma and returned to normal within 24 hours
      without significant potassium replacement. In bivariant analysis, age, admission
      systolic blood pressure, cardiac injury, and serum epinephrine level were
      associated with admission serum potassium value (K1), whereas sex, mechanism of
      injury, number of organ systems injured, blood glucose, serum alcohol, arterial
      pH, Injury Severity Score, trauma score, estimated blood loss, and urine
      potassium were not significantly related to K1. But in a multiple regression
      model, the only significant independent variables were age, arterial pH, and
      serum epinephrine level.

PMID- 8284718
TI  - Intravenous ethanol for alcohol detoxification in trauma patients.
AB  - Traumatic injury frequently follows alcohol abuse. Between October 1, 1988 and
      January 31, 1992, 2,219 patients were admitted to the Trauma Service at the
      University Medical Center of Eastern Carolina-Pitt County. Of the 1,602 who were
      tested for serum ethanol, 685 (43%) were found to have measurable levels. Thirty
      seven patients had alcohol withdrawal and were treated with intravenous ethanol;
      34 were male (21 black, 13 white) and 3 female (1 black, 2 white), with an
      average age of 46 years. Those who had withdrawal had an average serum ethanol
      level, on presentation, of 239 mg/dL (N = 34). Fourteen patients were involved in
      motor vehicle crashes, seven were pedestrians struck by cars, and the remaining
      16 had various traumatic mechanisms of injury. The most common injuries were long
      bone fractures and blunt abdominal trauma. The length of ethanol therapy averaged
      4 days. A majority of patients had a favorable response to treatment. Relative
      contraindications to i.v. ethanol therapy were CNS trauma, liver disease, and
      pancreatitis. i.v. ethanol is a safe and effective method of alcohol
      detoxification in the trauma patient.

PMID- 8284719
TI  - Comparison of venography, duplex imaging, and bilateral impedance plethysmography
      for diagnosis of lower extremity deep vein thrombosis.
AB  - Twenty-four consecutively hospitalized patients with clinical evidence of lower
      extremity deep vein thrombosis (DVT) had blinded ipsilateral ultrasonographic
      duplex imaging (US), contrast venography (VG), and a one-time bilateral impedance
      plethysmography (IPG) examination. The cases of eight (33%) of the study patients
      were thought to be complicated due to a prior history of DVT or the presence of
      ipsilateral inguinal adenopathy. Interpretable test results were obtained for
      100% of the US examinations, 88% of the VG studies, and 75% of the IPGs. One
      additional subject, included in our study for statistical analysis, had an
      unblinded false-negative US examination; in this case DVT was shown by VG but
      could not be seen on US despite the radiologist's prior knowledge. The
      sensitivities, specificities, and 95% confidence intervals for the three studies
      were as follows: US, 92% (81% to 103%) sensitivity, 100% (99% to 101%)
      specificity; VG, 100% (99% to 101%) sensitivity, 75% (58% to 96%) specificity;
      IPG, 50% (30% to 70%) sensitivity, 83% (68% to 98%) specificity. Of the six
      indeterminate IPG studies, four (67%) occurred in complicated cases. These data
      suggest that US should be the first-line noninvasive screening study done for
      evaluation of suspected DVT, especially in complicated cases.

PMID- 8284720
TI  - Review of 333 living donor nephrectomies.
AB  - We reviewed the operative complications in 333 living related donor nephrectomies
      done at our institution over the past 12 years. The overall complication rate was
      17.1%; only three patients (0.9%) had major complications, and none died. The
      major complications were a delayed splenectomy because of bleeding, an
      adrenalectomy, and acute renal failure in one patient in the immediate
      postoperative period. We concluded that donor nephrectomy done through a flank
      incision results in minimal morbidity.

PMID- 8284721
TI  - Are emergency physicians too stingy with analgesics?
AB  - Several recent reports suggest that emergency physicians do not use adequate
      analgesia for patients with acutely painful conditions in the emergency
      department (ED). To quantify the extent of this problem, we retrospectively
      studied 401 patients who were treated for acute fracture over a 17-day period in
      eight area-wide emergency departments. Patient age, fracture site, and ED setting
      (urban or suburban, teaching or nonteaching) were noted. Only 121 patients (30%)
      received analgesics while in the ED; neither fracture site, ED setting, or
      patient age significantly altered analgesic dispensing practices. We conclude
      that inadequate use of analgesics in patients who come to the ED for treatment of
      acute fractures is widespread and that efforts aimed at improving the appropriate
      use of analgesics in the ED are warranted.

PMID- 8284722
TI  - Malaise in medicine: we don't teach what we do.
AB  - I tested the hypothesis that the most frequently used textbooks of internal
      medicine are inadequate in their coverage of the evaluation and management of
      common complaints and management problems of primary care. Fourteen common
      complaints (symptoms) and nine common management problems (diseases) representing
      20% to 40% of primary care patient visits were identified, and seven major
      textbooks of internal medicine were reviewed to assess the amount and extent of
      coverage of these topics. The average number of pages devoted to all 14 major
      problems was about 30, or 1.5% of the total. About 40 (2%) of the pages addressed
      the nine management problems. The minimal amount of coverage devoted to these
      topics could be taken as evidence of the lack of respect, importance, and
      emphasis ascribed to them. The lack of instruction in these areas may enhance
      malaise in primary car medicine due to inadequate instruction in the needed data
      base and skills and the resultant patient dissatisfaction.

PMID- 8284723
TI  - Varicella immunity and clinical disease in HIV-infected adults.
AB  - Varicella is an infrequent but potentially severe infection in adult HIV-infected
      patients. We reviewed five cases of varicella in HIV-seropositive men; two were
      complicated by severe headache and meningismus, and one of these patients also
      had hepatitis and thrombocytopenia. All five patients responded well to acyclovir
      therapy, but one patient had dermatomal zoster 2 years later, and another failed
      to have detectable antibody after infection. We also performed a serosurvey on
      181 consecutive HIV-infected patients presenting themselves for evaluation. A
      total of 95% of these patients had demonstrable antibody to varicella-zoster
      virus. Immune status to varicella did not correlate with the declining CD4 count,
      which was well preserved even in patients with fewer than 200 CD4 cells/mm3.

PMID- 8284724
TI  - Dome-shaped lesion on chest radiograph: retroperitoneal abscess dissecting
      through the posterior chest wall.
AB  - A 50-year-old man with an 8 x 4 cm mass on the posterior chest was found to have
      a large retroperitoneal abscess due to Klebsiella pneumoniae. The abscess
      dissected through the right lower lobe of the lung and the posterior chest wall
      to produce a subcutaneous mass. The source of the posterior chest wall mass
      appeared to be a perinephric abscess. A dome-shaped lesion above the right
      hemidiaphragm on chest radiograph resolved immediately with surgical drainage,
      suggesting that an abscess should be a prime consideration when one observes such
      a lesion on a chest film.

PMID- 8284725
TI  - Crohn's disease complicating cystic fibrosis.
AB  - We report the 10th known case of Crohn's disease associated with cystic fibrosis.
      Because the symptoms of Crohn's disease may easily be confused with those of
      cystic fibrosis, this association probably exceeds that predicted by existing
      prevalence data.

PMID- 8284726
TI  - Unmasking a patent foramen ovale during recurrent paradoxical cerebral embolism.
AB  - A patient with an acute ischemic stroke had an interatrial septal aneurysm shown
      by transesophageal echocardiography. Interatrial shunting, compatible with a
      patent foramen ovale, was observed on a follow-up study after a second stroke.
      This was seen in association with a right atrial thrombus. This case illustrates
      that an interatrial septal aneurysm serves as a marker for potential interatrial
      shunting, which can lead to paradoxical cerebral embolism.

PMID- 8284727
TI  - Very brief transient ischemic attack.
AB  - TIA is an important risk factor for ischemic stroke. Early diagnosis and
      management can result in a significant reduction in the risk of subsequent
      stroke. We report the case of a 54-year-old man who developed a 5-second episode
      of leg weakness and in whom a tight stenosis of the appropriate carotid artery
      was found. TIAs can sometimes be brief and have an atypical presentation,
      requiring a high level of suspicion for early diagnosis.

PMID- 8284728
TI  - Cardiogenic shock due to progression of cutaneous T-cell lymphoma.
AB  - We describe a patient with progressive cutaneous T-cell lymphoma (CTCL) and
      development of subacute cardiac failure. Symptomatic lymphomatous involvement of
      the heart may be more common in patients with CTCL than in other lymphomas
      because the former is more likely to be associated with circulating tumor cells
      and hematogenous spread to the myocardium. No single symptom or sign is highly
      predictive of cardiac involvement, but unexplained tachyarrhythmias, conduction
      disturbances, low voltage on ECG, and unexplained cardiac enlargement should
      arouse clinical suspicion. Although echocardiography may be helpful in suggesting
      cardiac involvement, endomyocardial biopsy should be considered in patients with
      a reasonable chance of responding to chemotherapy or radiation.

PMID- 8284729
TI  - Streptococcus milleri as a cause of antecubital abscess and bacteremia in
      intravenous drug abusers.
AB  - S milleri should be added to the list of organisms producing wound infections in
      parenteral drug addicts. Recovery of "viridans streptococci" from an antecubital
      aspirate should prompt the clinician to request speciation, examine closely for
      abscess formation, and anticipate prolonged antibiotic therapy.

PMID- 8284730
TI  - Spontaneous conversion of supraventricular tachycardia followed by
      electromechanical dissociation.
AB  - We present this case to emphasize the potentially fatal outcome of
      supraventricular tachycardia in infancy, particularly if it has been undiagnosed
      for several days. Certainly, careful monitoring needs to take place during any
      attempt at cardioversion or any other noxious stimulation of the patient.
      Bicarbonate therapy should be provided if metabolic acidosis is present.
      Restoration of sinus rhythm may not guarantee an immediate return of normal
      cardiac function.

PMID- 8284731
TI  - Endometrioma: sonographic classification.

PMID- 8284732
TI  - Family burden in schizophrenia: implications for services.

PMID- 8284733
TI  - Economic evaluation in health care: an introduction for psychiatrists.
AB  - The objective of this paper is to provide an understanding of economic evaluation
      as applied to health care. A number of methodological issues are explained.
      Measurement issues are outlined and examples given.

PMID- 8284734
TI  - The relationship of social network deficits with deficits in social functioning
      in long-term psychiatric disorders.
AB  - It has been suggested that deficits or impairments in social functioning may
      explain the depleted support networks of the mentally ill. With this in mind, 145
      long-term users of day care psychiatric facilities, 57% of whom had a life-time
      diagnosis of schizophrenia, were examined to determine whether deficits in social
      and survival skills explained deficits in their social networks. Compared with
      patients with acute depression, long-term patients had smaller social networks.
      There was a very small but statistically significant association between observer
      ratings of deficits in social functioning (daily social and living skills) and
      self-reported family social networks size. Behavioural problems were also
      associated with smaller family networks. Among the long-term patients, duration
      of service contact and type of disorder (affective vs nonaffective psychosis)
      were not related to network size. These preliminary findings are discussed.

PMID- 8284735
TI  - Are social deprivation and psychiatric service utilisation associated in neurotic
      disorders? A case register study in south Verona.
AB  - Measures of service utilisation from the South Verona psychiatric case register
      in North-East Italy for the years 1983, 1986 and 1989 were used to identify
      possible associations with sociodemographic variables from the 1981 census for
      neurotic disorders. There were no consistent patterns of associations between
      local social and demographic predictors and rates of psychiatric service
      utilisation. This contrasts markedly with the associations found previously in
      England (for all psychiatric admissions) and in Italy (for various measures of
      service utilisation concerning contacts both in and outside hospital for
      schizophrenic as well as for all psychiatric patients) where social deprivation
      factors proved to be strong predictors of service use.

PMID- 8284736
TI  - Work environment and schizophrenia: an extension of the arousal hypothesis to
      occupational self-selection.
AB  - The present study investigated a possible mechanism underlying the occupational
      self-selection of future schizophrenic patients prior to their first admission.
      More precisely, we explored whether schizophrenic patients are more likely than
      other psychotic patients to work in environments with a low potential for arousal
      (low complexity environments) in the last full-time job that preceded their
      hospitalization. All first admissions with psychotic symptoms to 15 hospitals
      providing inpatient psychiatric services in the Baltimore-Washington area were
      surveyed during a 6-year period. Patients diagnosed with schizophrenia were
      compared to patients diagnosed with bipolar disorder and other psychotic
      disorders to evaluate the suspected association. Study participants were assessed
      with a modified version of the Diagnostic Interview Schedule. Standard survey
      questions were used to assess occupational background. A measure based on the
      dictionary of occupational titles (DOT) was used to estimate the degree of
      complexity to which patients had been exposed in their last full-time occupation.
      Data were analyzed using multinomial logistic regression. After adjustment for
      age, gender, marital status, unemployment, socioeconomic status, hospital type,
      and physical demands and hazards on the job, patients with schizophrenia were
      more likely to have been working in low complexity environments in their last
      full-time jobs (e.g., janitors, gardeners, guards) than patients with bipolar
      disorder or with other psychotic disorders. Alternative explanations and
      potential implications regarding which work environments might be best suited to
      the social behavior of patients with schizophrenia are examined.

PMID- 8284737
TI  - The ICD-10 symptom checklist: a companion to the ICD-10 classification of mental
      and behavioural disorders.
AB  - The ICD-10 Symptom Checklist is a semi-structured diagnostic instrument intended
      for clinicians' assessment of F0-F6 categories in the ICD-10 Classification of
      Mental and Behavioural Disorders. The instrument was preliminarily tested at the
      St. Louis site during its participation in the field trials of the ICD-10
      Diagnostic Criteria for Research. The Checklist was found to be a reliable
      diagnostic tool (overall kappa 0.72) within the constraints of the
      interviewer/observer reliability study design. More rigorous tests of the
      psychometric properties of the instrument are necessary.

PMID- 8284738
TI  - Depression in three populations in the Basque country--a comparison with Britain.
AB  - A psychiatric survey in three regions of the Basque Autonomous Community aimed to
      replicate two British surveys, in London and a rural area of Scotland,
      investigating both prevalence of psychiatric disorder and its relationship with
      certain key psychosocial factors. The Spanish rural-urban differences in rates of
      depression and anxiety closely paralleled the earlier British results. As in
      Britain, Spanish rural rates of depression were lower among those most integrated
      into the traditional family ways of life, but in contrast to Britain the urban
      rates did not vary with social class or the presence of children at home. As in
      Britain, severe life event and major difficulties were associated with onset of
      depression, and varied in prevalence and type with degree of integration with the
      traditional lifestyle. The protective role of intimate confiding with a partner
      against depressive onset was confirmed among non-churchgoers in Bilbao, but not
      among churchgoers, while in the rural samples there was only a nonsignificant
      trend.

PMID- 8284739
TI  - Psychometric properties of the parental bonding instrument in a Spanish sample.
AB  - The Parental Bonding Instrument was translated into Spanish and administered to a
      sample of 205 Spanish primiparae 3 days after childbirth. Reliability, factorial
      structure and predictive validity for affective disorders were evaluated. The
      Spanish version of the PBI has psychometric features similar to those described
      in other cultures. However, the results suggest that in future research the
      predictive power of the "Control" factor in affective disorders might be improved
      by splitting it into two subfactors: "Overprotection" and "Restraint".

PMID- 8284741
TI  - [9th Annual meeting of the German Society for Vascular Surgery. Heidelberg, 26-29
      May 1993. Proceedings].

PMID- 8284740
TI  - Suicidal attempts and ideations among adolescents and young adults: the
      contribution of the father's and mother's care and of parental separation.
AB  - Parental care was analyzed separately with the PBI for both father and mother or
      their surrogate to assess its association with suicidal behavior (attempt or
      serious ideation). The study was conducted on two French-speaking samples from
      Montreal: the first included 2,327 high school students and the second 701 young
      adults (18 to 24) reached by phone. Results showed poor care of father to be
      highly associated with suicidal behavior in the highschool group. Poor care of
      the mother and parental divorce obtained a lower association. In the second
      sample, only poor care of the father was significantly associated with suicidal
      behavior. The conclusion is that more attention should be focused on the father
      and that parental divorce may have a short-term effect but not a lasting
      influence when poor care is absent.

PMID- 8284742
TI  - [Therapy of Ewing's sarcoma].
AB  - Therapy of Ewing's sarcoma requires a qualified clinical, radiological, and
      pathohistological diagnosis and, in particular, an optimal therapy by an
      experienced team of oncological specialists. Important prognostic factors are the
      presence of hematogenous metastases at diagnosis, the initial tumor volume, the
      response to chemotherapy, and adequate local therapy. Presently, cure rates of
      more than 60% can be achieved for localized Ewing's sarcoma by combination of
      local therapy and chemotherapy. The four-drug combination VACA (vincristine,
      actinomycin D, cyclophosphamide, adriamycin) can be considered as cytostatic gold
      standard. More aggressive regimens (VAIA, EVAIA, autologous bone marrow
      transplant) may be beneficial in subgroups and are under investigation.
      Concerning local therapy adequate radiotherapy plays a major role and achieves
      the same survival rates as radical surgery, comparable patient selection
      provided. Several factors have impact on radiotherapeutic results, especially
      total dose (45 Gy large volume, 55 Gy to the primary tumor), target volume
      (safety margin at least 2 cm according to the pretreatment volume, at least 5 cm
      in proximal and distal extension of long bones), timing of radiotherapy (as early
      as possible) and quality of treatment. Radiotherapy as sole local treatment is
      indicated in inoperable lesions (spine, sacrum, skull) and in small, good
      responding tumors. High-risk patients should receive combined radiotherapeutic
      surgical treatment, preferably as pre-operative irradiation. The value of
      hyperfractionation is not yet proven despite theoretical advantages.

PMID- 8284743
TI  - [Preoperative low-dose-rate versus high-dose-rate brachytherapy in stage IB
      cervix cancer. An efficacy study].
AB  - In women with stage IB (FIGO) carcinoma of the cervix, the authors investigated
      the efficacy of the manual low-dose rate (LDR) and afterloading high-dose rate
      (HDR) technique in terms of local freedom from tumor. It was found that in the
      194 patients treated with the low-dose rate LDR-technique (computed dose point A
      23.5 GY; point B 4.7 Gy), the surgical specimen was free of tumor in 37%. Among
      the 161 patients treated with the high-dose rate technique (point A11 Gy; point B
      2 Gy), 41% of the surgical specimens were free of tumor. Follow-up examinations
      in the group receiving LDR-brachytherapy were carried out within a period of
      between ten and 90 months after treatment (average: 30.76 months). In 84% of the
      cases, NED was established. In the patient group treated with HDR-brachytherapy,
      follow-up examinations performed within a period of between six and 42 months
      after treatment (average 17.17 months), NED was found in 90%.

PMID- 8284744
TI  - [Radiation sensitivity of the normal bile duct during high dose rate afterloading
      irradiation with Iridium 192. Experimental studies in pigs].
AB  - This animal study was designed to assess the tolerance of the normal bile duct to
      a single intraluminal high-dose-rate afterloading irradiation. This information
      is essential for treatment recommendations in irradiation therapy of malignant
      bile duct stenoses. In 16 pigs bile duct catheters were inserted surgically. Over
      these devices single intraductal doses of 7.5 Gy and 15 Gy were applied using an
      iridium-192 source. After a period of two to three months the bile ducts and the
      surrounding structures were investigated by means of cholangiography,
      angiography, and macropathological and histological investigations. A single
      intraductal dose of 7.5 Gy leads to a slightly scarred shrinkage of the bile duct
      with sclerosis and obliteration of the capillary vessels. Vasculitis and necrosis
      of the bile duct wall are still evident three months after irradiation. A single
      dose of 15 Gy leads to severe lesions with widespread necroses of the bile duct
      wall which tend to bleed, and result in a high degree of shrinkage of the bile
      duct. The radiation damage is most prevalent near the papilla and in the narrow
      segments near the liver. Single intraluminal high-dose-rate afterloading doses of
      7.5 and 15 Gy cause significant lesions and complications at the bile ducts. As
      the intact bile duct is the Achilles heel of intraductal therapy, considerably
      lower single doses are recommended for a fractioned treatment.

PMID- 8284745
TI  - Brain tumor delineation based on CT and MR imaging. Implications for radiotherapy
      treatment planning.
AB  - This paper deals with the impact MRI may have on radiotherapy treatment planning
      of brain tumors. The authors analyzed differences in size and position of
      treatment fields as indicated by three observers (two radiotherapists and one
      neuroradiologist) using CT or MR based radiotherapy planning procedures for
      cerebral-gliomas. Large differences in field size and position were found in non
      CT contrast enhancing tumors, all low grade gliomas. Small differences were found
      in contrast enhancing lesions including the high grade gliomas. We conclude that
      implementation of MRI in radiotherapy treatment planning leads to a greater
      precision in treatment fields for non CT contrast enhancing lesions.

PMID- 8284746
TI  - [An irradiation technique for the right half of the rat lung using 9 MV photons
      from a linear accelerator].
AB  - Prior to the irradiation of inner organs of animal models with linac photons the
      organ has to be related to the beam portal using a radiation therapy simulator.
      This relation becomes possible in an easy way by the method and a special
      irradiation tray, which are described in this paper.

PMID- 8284747
TI  - X-ray induced DNA double-strand breakage and rejoining in a radiosensitive human
      renal carcinoma cell line estimated by CHEF electrophoresis.
AB  - Cell intrinsic radiosensitivity is of great importance in radiation therapy, but
      its molecular basis is still uncertain. Since DNA double strand breakage is
      considered to be the most important lesion related to cell death induced by
      ionizing radiation, the relationship between DNA double-strand breakage, repair
      and cell survival was investigated in three cell lines: Chinese hamster cell (CHO
      K1), human fibroblast and human renal carcinoma (Tu 25). The D0 values after X
      irradiation were 1.73, 1.23, and 0.89 Gy, respectively, showing that Tu 25 was
      the most sensitive among them. DNA double-strand breaks were measured by CHEF
      electrophoresis, the initial yield of double-strand break per dose in the three
      cell lines was almost the same, and no correlation to cell survival was found.
      However, the rejoining capacity for DNA double-strand break differed. After a
      dose of 20 Gy, the repair rate was markedly lower in Tu 25, with a half repair
      time of 40 min, as compared with the other two cell lines with half repair times
      of 15 min. The results strongly supported the correlation between the repair
      capacity for DNA double-strand break and cell survival. It was concluded that DNA
      repair capacity is one of the determinants of cell radiosensitivity. Estimation
      of DNA double-strand break rejoining by CHEF was suggested as a predictive assay
      for radiosensitivity of human tumor cells.

PMID- 8284748
TI  - [Radiochemotherapy in the treatment of metastatic renal cell carcinoma].
AB  - Enhancement of the radiation effect with Epirubicin (20 mg day 1 to 5 and 29 to
      33) in a metastasis of a renal cell carcinoma will be presented. The published
      experimental results are also encouraging.

PMID- 8284749
TI  - Intracoccygeal and pericoccygeal glomus bodies and their relationship to
      coccygodynia.
AB  - BACKGROUND: Coccygodynia is an uncommon condition of diverse causes. A few cases
      were attributed to so-called pericoccygeal glomus tumors. However, the
      pericoccygeal soft tissues normally contain numerous small glomus bodies and a
      larger one known as the glomus coccygeum, which can reach several millimeters in
      diameter. Most reported cases of alleged pericoccygeal glomus tumors represent
      normal, incidentally discovered coccygeal glomus bodies. Recently, an
      intracoccygeal glomus tumor was reported as a cause of coccygodynia. However, we
      suspected that glomera can also occur normally within the coccyx itself. METHODS:
      Twenty coccyges from fetuses, newborns, infants, and adults were obtained at
      autopsy, embedded in toto, and examined histologically in step sections. RESULTS:
      Intracoccygeal glomera were present in six of the nine pediatric specimens and
      all 11 adult specimens. All were microscopic structures, and none appeared to
      have caused bony destruction or erosion. They did not differ from the structures
      previously reported as alleged intracoccygeal "glomus tumors." CONCLUSIONS:
      Pericoccygeal and intracoccygeal glomus bodies are normal findings in humans at
      all ages. They should not be mistaken for tumors, and their role in the
      pathogenesis of coccygodynia is questionable.

PMID- 8284750
TI  - Effects of trehalose in canine lung preservation.
AB  - BACKGROUND: The effect of trehalose on the preservation of canine lungs was
      studied with the use of Euro-Collins solution (ECS). METHODS: In group 1, five
      lungs were perfused and preserved with a modified ECS in which trehalose (35.0
      gm/L) was used instead of glucose. In group 2, six lungs were perfused and
      preserved with a modified ECS in which glucose was replaced by 70.0 gm/L
      trehalose. In group 3, six lungs were perfused and preserved with ECS. After
      preservation for 12 hours, left lung transplantation was performed. RESULTS: The
      PaO2 values in groups 1 and 2 at 130 minutes after reperfusion were 264.9 and
      257.5 mm Hg, respectively. These PaO2 values were significantly higher than the
      corresponding PaO2 value in group 3 (114.8 mm Hg). All the transplanted lungs in
      groups 1 and 2 had normal structures on histologic examination, whereas five of
      the group 3 lungs showed severe pulmonary edema. CONCLUSIONS: These findings show
      that trehalose is effective in the preservation of lungs for 12 hours.

PMID- 8284751
TI  - Heterotopic liver transplantation in rats: effect of intrahepatic islet isografts
      and split portal blood flow on liver integrity after auxiliary liver
      isotransplantation.
AB  - BACKGROUND: Auxiliary heterotopic liver grafts atrophy in the absence of portal
      venous inflow; evidence suggests that an islet-derived hepatotrophic factor may
      exist in the portal drainage. Here we examine the effects of intrahepatic islet
      isografts in maintaining hepatocyte integrity in Wistar Furth rats with one of
      several types of arterialized auxiliary liver isografts. METHODS: In type 1
      procedures the auxiliary liver was interposed into the recipient infrarenal vena
      cava and perfused through the graft portal vein with caval blood. In type 2
      procedures the donor infrahepatic vena cava was anastomosed end-to-side to the
      recipient vena cava and the recipient portal vein was diverted to the graft
      portal vein. Both types of auxiliary grafts were arterialized; bile duct drainage
      was through the duodenum. Syngeneic islets were isolated and embolized into the
      portal veins of one half of the donor type 1 or native type 2 livers (1500 to
      1700 islets). Finally, we performed six type 3 procedures in which a type 2
      procedure was performed except that the portal blood flow was split so that the
      portal vein receiving the splenic, gastric, pancreatic, and duodenal drainage
      supplied the native liver and that the common mesenteric vein supplied the
      auxiliary graft with equivalent portal blood flow. Atrophy in heterotopic and
      native livers were compared for the three models after 3 months. RESULTS:
      Intrahepatic islets in type 1 auxiliary liver isografts without portal venous
      inflow did not prevent graft atrophy. Conversely, native livers deprived of
      portal venous inflow in our type 2 procedures, regardless of the presence of
      intrahepatic islet isografts, atrophied relative to auxiliary liver grafts in
      which portal venous inflow was provided by diverting the recipient's portal vein
      to the graft. In type 3 recipients atrophy was greater in the native livers than
      in the grafts. CONCLUSIONS: The results of our study suggest that islet-derived
      factors are not sufficient to prevent hepatocellular atrophy in auxiliary rat
      liver transplantation models and that a potent hepatotrophic factor may exist in
      the venous drainage of the bowel distal to the duodenum.

PMID- 8284752
TI  - Intraluminal measurement of enteric mucosal perfusion: relationship to superior
      mesenteric artery flow during basal and postprandial states in the dog.
AB  - BACKGROUND: Several in vivo techniques that assess mucosal perfusion by
      intraluminal probes have recently been developed and validated, including laser
      Doppler flowmetry, reflectance spectrophotometry, and tonometry. METHODS: With
      these techniques, a canine model where the entire vascular supply to the
      jejunoileum was isolated as the superior mesenteric artery and vein was used to
      examine the relationship between enteric mucosal blood perfusion and adjusted
      decrements in arterial flow under fasting and postprandial conditions. RESULTS:
      Mucosal perfusion measured by laser Doppler flowmetry and reflectance
      spectrophotometry correlated linearly with decrements in superior mesenteric
      artery flow (r2 = 0.96 and 0.98, respectively); estimation of mucosal pH by
      tonometry decreased only after a critical level of arterial inflow was reached
      (less than 50% of baseline flow). Mucosal perfusion increased after the meal
      throughout the jejunoileum with unrestricted superior mesenteric artery flow.
      However, with restricted superior mesenteric artery flow, nutrient delivery to
      the jejunum was accompanied by increased mucosal perfusion at that level but by
      decreased perfusion in the distal ileum not exposed to nutrients. This latter
      response represents a distal to proximal redistribution of blood, i.e., an
      intramesenteric steal phenomenon. CONCLUSIONS: In vivo measurements of mucosal
      perfusion reflected changes in large mesenteric vessel blood flow. These
      intraluminal techniques discriminated between a normal and an impaired mesenteric
      circulation in an acute model and may have clinical application.

PMID- 8284753
TI  - Small intestinal sarcoidosis with massive hemorrhage: report of a case.
AB  - Sarcoidosis of the small intestine is a rarely described complication of systemic
      sarcoidosis. Although bleeding from sarcoidosis of the esophagus, stomach, and
      colon has been reported, massive bleeding from this condition in the small
      intestine has not been previously described. We present here the first case of
      hemorrhage from a jejunal sarcoid lesion that was unsuspected and undiagnosed
      until laparotomy with resection was performed. As with most pathologic conditions
      of the small intestine, preoperative diagnosis is difficult. Furthermore, the
      refractory nature of bleeding from this lesion made resection necessary in this
      patient, suggesting the need for similar therapy in other affected patients.

PMID- 8284754
TI  - Malignant mixed tumor (carcinosarcoma) of the pancreas: a case report supporting
      organ-induced differentiation of malignancy.
AB  - BACKGROUND: We present an unusual case of a malignant mixed tumor
      (carcinosarcoma) of the head of the pancreas that was surgically resected and
      whose tissue pathologic condition supported the concept of organ-induced
      differentiation of malignancy. METHODS: After a pancreaticoduodenectomy, tissue
      sections from various anatomic regions of the tumor were studied by routine
      histologic examination and immunocytochemistry. Genomic DNA from various regions
      of the tumor was extracted and digested with Hpa II, and a 511 bp region of the
      hypoxanthine phosphoribosyltransferase gene was amplified with the polymerase
      chain reaction to assess clonality. RESULTS: The pathologic findings revealed
      areas of both adenocarcinoma and leiomyosarcoma, but these disparate areas were
      not randomly distributed but rather were polar in nature. The adenocarcinomatous
      areas localized to the tumor within the head of the pancreas, an area of normal
      ontogenetic glandular development, whereas the leiomyosarcomatous areas localized
      to regions of the tumor infiltrating the duodenal wall, an area of normal
      ontogenetic smooth muscle development. Both the adenocarcinomatous and the
      leiomyosarcomatous areas showed evidence of monoclonality and clonal identity.
      CONCLUSIONS: This interesting polar distribution of histologic patterns
      illustrated by this malignant mixed tumor (carcinosarcoma) supports the
      hypothesis of organ-induced differentiation of malignancy.

PMID- 8284755
TI  - Detection of intraabdominal abscess by serum lysozyme estimation.
AB  - BACKGROUND: The failure of new, innovative, and often expensive tests to show the
      presence of intraabdominal infection caused us to reexamine the value of an
      inexpensive and almost forgotten one. Lysozyme is a bacteriolytic enzyme located
      within the lysosomes of phagocytic cells including leukocytes. METHODS: We
      measured serum concentrations of lysozyme by a standard turbidimetric method in
      both a murine model of intraabdominal infection and in trauma patients with
      intraabdominal abscesses or other acquired infections. RESULTS: In mice with
      intraabdominal abscess secondary to cecal ligation and puncture (n = 35) serum
      lysozyme activity increased compared with sham-operated controls (n = 20; p <
      0.001). In trauma patients with intraabdominal abscess after injury and surgery
      (n = 19), there was also an increase in serum lysozyme activity compared with
      controls (n = 15; p < 0.001) or with patients with lung infection (n = 21; p <
      0.001). The increase of serum lysozyme activity occurred before intraabdominal
      sepsis was clinically apparent. CONCLUSIONS: In this study, serum lysozyme
      concentration has a high specificity related to the presence of an intraabdominal
      abscess and is an indirect measure of the sequestration of leukocytes to the site
      of an established or developing collection of intraabdominal pus. The estimation
      of serum lysozyme may be an aid to differentiate critically ill patients with a
      potential occult intraabdominal abscess.

PMID- 8284756
TI  - Total pancreatic duct drainage for leakproof pancreatojejunostomy.
AB  - BACKGROUND: We describe a new method to achieve a safe and leakproof
      pancreatojejunostomy based on the hypothesis that anastomotic leakage will not
      occur if no accumulation of pancreatic juice precipitates it. METHODS: Forty
      eight patients underwent end-to-side pancreatojejunostomy with a pancreatic duct
      tube designed with an expanded segment to prevent slippage, which drained
      externally via the gastrostomy. The tube was tied to the main pancreatic duct
      with absorbable suture, which ensured complete external drainage of pancreatic
      juice during the postoperative healing period. After the tie was absorbed, the
      tube was simply removed. RESULTS: Minor leakage of the pancreatojejunostomy
      developed in only two of the 48 patients, and both healed spontaneously without
      surgical intervention. No morbidity or death was related to the
      pancreatojejunostomy. CONCLUSIONS: This method is safe, because even if leakage
      does occur the intestinal fluid contains no pancreatic juice.

PMID- 8284757
TI  - External iliac ligation and axillary-bifemoral bypass for blue toe syndrome.
AB  - BACKGROUND: This report describes six patients with atheroemboli to both lower
      extremities that originated from the abdominal aorta. All patients had severe
      bilateral rest pain and ulceration or gangrene. Each had severe coronary artery
      disease and other medical problems, which precluded direct aortic reconstruction.
      METHODS: Ligation of the external iliac arteries was performed to prevent
      continual passage of emboli into the lower extremities. Revascularization was
      effected by axillary-bifemoral bypass. RESULTS: Initial limb salvage was
      accomplished in twelve threatened extremities. One patient required a single toe
      amputation. One axillary graft failed after 3 months and was successfully
      replaced with a contralateral graft. These patients have been followed for up to
      52 months without limb loss; the mean follow-up is almost 2 1/2 years.
      CONCLUSIONS: In patients with severe coronary artery disease and blue toe
      syndrome, the combination of external iliac ligation and axillary-bifemoral
      bypass is an effective and durable procedure to prevent worsening ischemia and to
      salvage threatened lower extremities.

PMID- 8284758
TI  - Amount of alcohol is an important determinant of the severity of acute alcoholic
      pancreatitis.
AB  - BACKGROUND: Does the amount of recently consumed alcohol correlate with the
      severity of acute alcoholic pancreatitis? METHODS: One hundred one consecutive
      episodes of acute pancreatitis (AP) were prospectively studied. Seventy-three
      were alcoholic AP episodes; 40 patients had their first alcoholic AP episode. A
      standard personal interview was used to determine the alcohol consumption during
      2 months and during 1 week before AP. The severity of AP was evaluated according
      to the Ranson criteria, the serum C-reactive protein (CRP) concentration measured
      24 to 48 hours after admission, the length of the hospital stay, the development
      of complications, and the mortality rate. RESULTS: In the 40 patients having
      their first alcoholic AP episode, the reported 2-month alcohol consumption
      correlated significantly with the number of positive Ranson criteria (correlation
      coefficient r = 0.44, p < 0.01), serum CRP concentration (r = 0.51, p < 0.001),
      and the length of the hospital stay (r = 0.45, p < 0.01). Complications occurred
      in eight of 14 patients with 2-month alcohol consumption of more than 5000 gm as
      compared with one of 14 patients with consumption of less than 2000 gm (p <
      0.05). In the same 40 patients the 1-week alcohol consumption correlated with the
      number of positive Ranson criteria (r = 0.40, p < 0.05) and serum CRP
      concentration (r = 0.37, p < 0.05). Of the 12 patients who had consumed more than
      1000 gm alcohol during the last week before admission, two died and complications
      developed in six (50%), as compared with none (p < 0.05) and six (21%),
      respectively, of those who had consumed less than 1000 gm. No significant
      correlations were observed between the reported alcohol consumption and any of
      the severity parameters in the 33 patients with recurrent episodes of alcoholic
      AP. CONCLUSIONS: The amount of alcohol consumed may be an important determinant
      of the severity of the first alcoholic AP episode but not of recurrent alcoholic
      AP.

PMID- 8284759
TI  - Prognostic factors for tumor response and limb recurrence-free interval in
      patients with advanced melanoma of the limbs treated with regional isolated
      perfusion with melphalan.
AB  - BACKGROUND: At this time little is known about prognostic factors for tumor
      response and subsequent limb recurrence-free interval in patients suffering from
      advanced melanoma of the limbs who were treated with regional isolated perfusion.
      METHODS: A retrospective analysis was done, with a logistic regression model and
      a Cox proportional hazard analysis, looking at possible patient-, tumor-, and
      treatment-related prognostic factors in all 120 patients with advanced melanoma
      of the limbs who were treated with regional isolated perfusion with melphalan in
      the period 1978 to 1990 at our institutions. RESULTS: Complete remission was
      achieved in 65 patients (54%) with a median duration of 9+ months (range, 1 to
      97+ months), and partial remission was seen in 30 patients (25%). Prognostic
      factors for complete remission were multiple versus single perfusion schedule,
      the absence of regional node involvement, and leg versus other tumor sites. The 3
      year limb recurrence-free interval was 38%. Factors associated with this interval
      were one as opposed to more than one lesion, complete remission after perfusion,
      and female sex. Patients exhibiting complete remission after perfusion had a
      better overall 3-year survival rate than had patients without complete remission
      (60% vs 35%; p = 0.0012). CONCLUSIONS: In the present study prognostic factors
      for tumor response and limb recurrence-free interval could be determined. A
      multiple perfusion schedule may be more effective in providing complete remission
      in patients undergoing regional isolated perfusion than single perfusions are.

PMID- 8284760
TI  - Influence of renal artery blood flow on renal function during aortic surgery.
AB  - BACKGROUND: This study was undertaken to determine the true incidence of renal
      impairment after aortic surgery and its association with intraoperative
      fluctuations in renal artery blood flow and cardiac output. METHODS: Direct
      measurements of renal artery blood flow were undertaken with electromagnetic
      flowmetry in 19 patients undergoing elective infrarenal aortic surgery. Renal
      function was assessed before and after operation by measurement of creatinine
      clearance. RESULTS: Twelve patients (63%) had renal impairment as defined by a
      40% or greater reduction in creatinine clearance after operation. This group of
      patients had significantly lower renal artery blood flow during the period of
      aortic cross-clamping than had those who preserved their renal function (p <
      0.001). CONCLUSIONS: Renal impairment is common after infrarenal aortic surgery
      and may be a result of intraoperative ischemia secondary to reduced renal artery
      blood flow.

PMID- 8284761
TI  - Expression of CA 15.3 protein in the cyst contents distinguishes benign from
      malignant pancreatic mucinous cystic neoplasms.
AB  - BACKGROUND: Inflammatory pseudocysts, serous cystadenomas, and mucinous cystic
      tumors comprise most cystic lesions of the pancreas. The mucinous tumors include
      mucinous cystic neoplasms, which are benign on histologic examination but have
      the potential for malignant transformation, and mucinous cystadenocarcinomas.
      Accurate preoperative classification of pancreatic cysts with clinical and
      radiologic criteria is often impossible, and as a result many cystic tumors are
      inappropriately treated as pseudocysts. Analysis of percutaneous needle-aspirated
      cyst fluid for tumor markers, enzymes, viscosity, and cytologic study has been
      proposed as a useful modality to distinguish mucinous from nonmucinous cystic
      lesions. However, no reliable cyst fluid parameter distinguishes benign from
      malignant mucinous tumors. METHODS: The concentration of the tumor marker CA 15-3
      was measured by immunoassay in cyst fluid from six pseudocysts, five serous
      cystadenomas, three mucinous cystic neoplasms, and six mucinous
      cystadenocarcinomas. RESULTS: The concentration of CA 15-3 in the cyst fluid of
      mucinous cystadenocarcinomas was higher (mean, 178 units/ml; range, 40 to 392)
      than that of mucinous cystic neoplasms (mean, 4.7 units/ml; range, 0 to 14),
      serous cystadenomas (mean, 9.2 units/ml; range, 0 to 32), and pseudocysts (mean,
      15.3 units/ml; range, 0 to 66). An upper cutoff value of 30 units/ml
      distinguished mucinous cystic neoplasms from mucinous cystadenocarcinomas with
      100% sensitivity and 100% specificity (p = 0.01). CONCLUSIONS: Production of CA
      15-3 appears to coincide with malignant transformation in pancreatic mucinous
      cystic neoplasms. We conclude that measurement of CA 15-3 levels in the cyst
      fluid is useful in the differentiation of benign from malignant pancreatic
      mucinous cysts.

PMID- 8284762
TI  - Preoperative laboratory screening based on age, gender, and concomitant medical
      diseases.
AB  - BACKGROUND: The purpose of this study was to determine the most efficient
      preoperative laboratory screening for elective surgery. METHODS: Five hundred
      twenty patients undergoing elective operations on the general, vascular,
      thoracic, and head and neck surgical services were eligible for the study. The
      patient characteristics evaluated were age, gender, race, American Society of
      Anesthesiologists physical status classification, ponderal index, presence of
      concomitant respiratory disease, coronary artery disease, other heart disease,
      kidney disease, endocrine disease, malignancy, peripheral vascular disease,
      hypertension, diabetes mellitus, and neuropsychiatric disease. Preoperative
      laboratory screening included electrolytes, blood urea nitrogen, creatinine, and
      glucose levels, hemogram, nutritional studies (total protein and albumin levels
      and total lymphocyte count), coagulation studies (prothrombin time, partial
      thromboplastin time, and platelet count), urinalysis, electrocardiogram, and
      chest radiograph. Univariate analysis was done by Pearson's Chi square with
      Yate's correction. Significant p values were adjusted with Bonferroni's
      correction. Multivariate analysis was done with stepwise logistic regression.
      RESULTS: Univariate analysis showed age, gender, and the specific concomitant
      illness were associated with specific abnormal preoperative laboratory test
      results. Similarly, multivariate analysis showed specific predictors based on
      these risk factors. CONCLUSIONS: Routine preoperative laboratory testing is
      neither useful nor cost-effective. Appropriate preoperative laboratory testing
      can be based on age, gender, concomitant medical diseases, and type of operation
      to be performed.

PMID- 8284763
TI  - Defining the surgical personality: a preliminary study.
AB  - Noting that noncognitive factors may be more predictive of success in a medical
      career than is intellectual ability or cognitive performance, we undertook a
      study to determine whether a surgical personality exists and to delineate the
      temperament and personality traits that contribute to its definition. The Krug
      Adult Personality Inventory, the Strelau Temperament Inventory, and Barclay's
      adjective checklist were administered to 110 physicians, 35 in a "controllable
      lifestyle" specialty, 28 in primary care, and 47 in surgery or a surgery
      subspecialty. In addition, participants completed a stress inventory. Results
      showed that surgeons form a distinct and homogeneous group based on temperament
      and personality traits. We suggest that noncognitive factors can be of use to
      medical educators in the selection, counseling, training, and evaluation of
      medical personnel.

PMID- 8284764
TI  - Reduction in the homologous blood requirement for abdominal aortic aneurysm
      repair by the use of preadmission autologous blood donation.
AB  - BACKGROUND: To evaluate the effectiveness of preadmission autologous blood
      donation (PABD) in reducing the homologous transfusion requirement of abdominal
      aortic aneurysm resection, the blood product requirements of 145 patients who
      underwent operation at Cleveland Clinic from September 1987 through May 1991 were
      reviewed. METHODS: A study group of 73 patients underwent aortic grafting for
      aneurysm after PABD. Intraoperative autotransfusion (IAT) was used routinely.
      Homologous blood requirements were compared to those of 72 patients at the same
      center who underwent similar operations using IAT alone. No significant
      differences were noted in age, gender, cardiovascular risk factors, operation
      complexity, intraoperative blood loss, or IAT volumes between the two groups.
      Mean aneurysm size of the study patients (5.4 cm) was slightly less than that of
      the comparison patients (6.0 cm) (p < or = 0.001). Patients in the study group
      received a mean of 1.9 units predeposited autologous blood. RESULTS: The mean
      discharge hematocrit (33.4%) and hemoglobin (11.0 gm/dl) levels of the study
      group were indistinguishable from those of the comparison group (33.3% and 11.1
      gm/dl, respectively). The homologous blood requirement of the study group was
      significantly less (median, 0; mean, 1.3 units/patient) than that of the
      comparison group (median, 1.5; mean, 1.9 units/patient) (p = 0.001). Furthermore,
      67% (49 of 73 patients) of the study group required no homologous blood although
      only 36% (26 of 72 patients) of the comparison patients avoided banked blood
      transfusions (p = 0.0004). No significant differences were found in platelet,
      fresh frozen plasma, or cryoprecipitate requirements between the study and
      comparison groups. CONCLUSIONS: PABD significantly reduces the homologous blood
      requirements for elective aortic aneurysm resection and, when used in combination
      with IAT, eliminates the need for homologous blood in at least two thirds of
      properly selected patients.

PMID- 8284765
TI  - Physiologic basis for the pharmacologic use of recombinant human erythropoietin
      in surgery and cancer treatment.
AB  - BACKGROUND: Recombinant human erythropoietin (rHuEPO) is approved for the
      treatment of the anemia of chronic kidney failure and anemia associated with
      zidovudine therapy of acquired immunodeficiency syndrome. In chronic kidney
      failure and other conditions such as cancer and hematologic malignancies, the
      endogenous erythropoietin response to anemia is blunted and rHuEPO might be
      beneficial in these conditions. METHODS: We reviewed preclinical and clinical
      trial results with rHuEPO in a variety of conditions. RESULTS: It is clear that
      chronic anemias of several causes respond to pharmacologic doses of rHuEPO.
      rHuEPO has been shown to enhance erythropoiesis before elective surgery, reduce
      the number of patients exposed to homologous blood at the time of coronary artery
      bypass grafting, reverse the anemia in most patients with cancer, and result in
      clinical benefit in 25% to 35% of patients with myelodysplasia. CONCLUSIONS:
      rHuEPO is important as a therapeutic means to correct anemia. rHuEPO is likely to
      be useful in correcting chronic anemias or anemias associated with chemotherapy,
      particularly in those patients with expected long-term survival. Issues to be
      resolved include the accurate prediction and targeting of rHuEPO therapy for
      patients most likely to respond.

PMID- 8284766
TI  - Serum and cellular factors in murine obstructive jaundice.
AB  - BACKGROUND: The present experiments were performed to determine whether serum or
      cellular factors are responsible for the immune suppression observed in biliary
      obstruction. METHODS: Male Lewis strain rats underwent bile duct ligation and
      division (BDL) or sham celiotomy (SC). Spleen cells (splenocytes) and lymph node
      cells (lymphocytes) were isolated 3 to 14 days later. Levels of direct and total
      serum bilirubin and total conjugated bile acids and response of BDL and SC
      splenocytes and lymphocytes to concanavalin A (Con A) and phytohemagglutinin were
      measured. Splenocytes from normal Lewis rats were then added to medium containing
      20 microliters, 40 microliters, and 100 microliters BDL or SC serum and incubated
      with Con A. BDL or SC splenocytes were injected into normal Lewis rats, and
      splenocytes from those rats were studied 24 hours later (adoptive transfer).
      Splenocytes from BDL and SC rats were separated into nylon wool adherent and
      nonadherent fractions and incubated with Con A and phytohemagglutinin. RESULTS:
      The mitogenic response to Con A and phytohemagglutinin was depressed in BDL
      splenocytes but normal in BDL lymphocytes. BDL serum suppressed the proliferative
      response of normal splenocytes, and adoptive transfer of cells produced
      immunosuppression. Removal of a nylon wool adherent fraction of cells restored
      the lymphoproliferative response in BDL splenocytes. CONCLUSIONS: The blastogenic
      response to phytohemagglutinin and Con A was decreased in BDL splenocytes. This
      effect was transferrable by both serum and cells. Removal of a subpopulation of
      splenocytes corrected the defect.

PMID- 8284767
TI  - Evidence for free radical-mediated lipid peroxidation at reperfusion of human
      orthotopic liver transplants.
AB  - BACKGROUND: Generation of toxic oxygen metabolites at reperfusion may contribute
      to the injury sustained as a consequence of harvest and ischemic preservation of
      organ allografts. Because there is a paucity of evidence that this mechanism is
      operative in human beings, we measured the generation of ethane into the exhaled
      breath as a biomarker of free radical-mediated lipid peroxidation in human liver
      transplantation. METHODS: A novel technique that increased the previous standard
      of sensitivity 100-fold was used to measure picomole quantities of ethane in
      exhaled breath of eight recipients undergoing human orthotopic liver
      transplantation. RESULTS: Ethane production correlated closely with the specific
      events of liver transplantation including the initial reperfusion of the
      allografts. In every case a twofold to threefold increase in ethane production
      was superimposed on a stable baseline immediately after reestablishment of portal
      vein blood flow through the donor liver. CONCLUSIONS: Ethane production was
      interpreted as evidence of hepatic lipid peroxidation, presumably mediated by
      toxic metabolites of oxygen occurring at reperfusion. This noninvasive approach
      allowed localization of the time point at which lipid peroxidation occurred and
      may facilitate quantification of lipid peroxidation mediated by free radicals and
      other toxic oxygen metabolites during operation.

PMID- 8284768
TI  - Portrait of a malpractice defendant: the demographics of liability.

PMID- 8284769
TI  - Federal law and laboratory referrals.

PMID- 8284770
TI  - Surgeon's bronze casts immortalize hands.

PMID- 8284771
TI  - Cell block doc. Medical practice inside the walls of the Texas prison system.

PMID- 8284772
TI  - Abortion fight demonstrates classic political tactics.

PMID- 8284773
TI  - Conference explores rise in female AIDS cases.

PMID- 8284774
TI  - Program educates teens about killer tans.

PMID- 8284775
TI  - Physiatrics at the forefront: physical medicine and rehabilitation in the 1990s.
AB  - Physiatry, a specialty title derived from the word "physical," is the second
      fastest-growing medical specialty in the United States. The interdisciplinary
      team-management system is the key to the success of physiatric services. The goal
      is to maximize functional outcome for physically challenged patients who have any
      of a broad scope of disorders causing disabilities or pain. Rehabilitation of
      these patients is cost-effective and provides improved quality of life for those
      treated. The job of the four excellent Physical Medicine and Rehabilitation
      (PM&R) training programs in Texas is to educate young physicians with knowledge
      regarding medicine, general science, electrodiagnostics, and allied health-care
      science. Young physiatrists may gravitate towards various subspecialties in the
      field or choose to provide a variety of services to assist other physicians in
      the management of patients over a prolonged period. In the age of managed
      competition, costs versus access, and quality-of-care issues, physiatrists must
      educate physicians, the public, legislators, and insurance carriers (federal,
      state, workers' compensation, and third-party) as to why rehabilitation should be
      included in any and every health-care plan.

PMID- 8284776
TI  - Annual economic costs attributable to cigarette smoking in Texas.
AB  - The costs attributable to smoking in Texas continue to rise. The most recent
      estimates show more than $4 billion in 1990 can be associated with the direct
      health-care costs from treatments for disease and the indirect costs associated
      with mortality and morbidity. The breakdown of these estimates for adults 35
      years and older shows 61% of the total costs was due to premature death caused by
      smoking, 29% due to direct health-care costs, and 9% attributable to indirect
      morbidity costs, which indicate lost wages caused by smoking-related illness. The
      1990 smoking-attributable deaths estimated at 24,600 far exceed the accumulated
      deaths, 9430 in 1991, caused by auto accidents, homicide, AIDS, alcohol, fires,
      cocaine, crack, heroin, and morphine. The estimates are prepared by The
      University of Texas M.D. Anderson Cancer Center Office of the Vice President for
      Health Policy for the Office of Smoking and Health, Bureau of Chronic Disease
      Prevention and Control, Texas Department of Health.

PMID- 8284777
TI  - Physicians' insensitivity to blame for managed care woes.

PMID- 8284778
TI  - TMA must take health plans to task.

PMID- 8284779
TI  - Educational program available on diabetic retinopathy.

PMID- 8284780
TI  - A nurse's Christmas Eve: the miracle.

PMID- 8284781
TI  - Health care reform.

PMID- 8284782
TI  - Legal issues for nurses. Shhhh! Confidentiality in the 90's.

PMID- 8284783
TI  - A significant percentage of normal T lymphocytes express HLA-DP in the peripheral
      blood.
AB  - HLA-DP expression has been widely investigated on T lymphocytes activated under
      different conditions. In the present study, a double staining procedure was used
      in flow cytometric experiments to define DP expression on normal peripheral blood
      T lymphocytes. In about two-thirds of the case analyzed, DP was expressed on a
      higher percentage of normal peripheral T lymphocytes than DR was. This was
      particularly true for 1 of the 16 cases investigated in which the percentage of T
      lymphocytes expressing DP was 46% and in which DP expression was mainly the
      prerogative of CD8+ and CD56+ lymphocytes.

PMID- 8284784
TI  - Functional dissection of the serological DR LYGUE and genotypic DRB1*1303
      specificities using a tetanus toxin-specific T-cell clone.
AB  - The DRB1 sequence of the homozygous cell line HAG (DR13-DwHAG-DQ7) represents a
      new DRB allele assigned DRB1*1103, whereas its DRB3 sequence corresponds to the
      previously described DRB3*0101 (DR52a) allele. The DRB1*1303 gene product is
      undetectable by current sera used in routine serology typing. We report here
      direct evidence that the MHC molecule encoded by the DRB1*1303 gene is functional
      in antigen presentation and in T-cell restriction. We describe a T-cell clone
      specific for tetanus toxin whose restriction pattern strictly follows the
      DRB1*1303 allele, as defined by oligonucleotide typing. It also follows the
      serologic reactivity with the serum LYGUE and also the DwHAG MLC-defined
      specificity pattern, with one exception. The potential functional sites for the
      DRB1*1303 gene product involved in T-cell restriction were deduced from sequence
      comparisons between DRB1*1303 and closely related DRB1 alleles. The relevant as
      substitutions were located within close proximity to each other on the HLA class
      II structural model. Our results demonstrate that 1) DRB1*1303 is functional in
      antigen presentation and T-cell restriction 2) the functional region involved in
      antigen presentation and T-cell restriction by DRB1*1303 can be defined
      structurally.

PMID- 8284785
TI  - Modulation of cell surface antigens and regulation of phagocytic activity
      mediated by CD11b in the monocyte-like cell line U937 in response to
      lipopolysaccharide.
AB  - Modulation of the cellular antigens and regulation of the phagocytic activity of
      the monocyte-like cell line U937 after culture with lipopolysaccharide (LPS) were
      investigated. CD14 expression was induced on the surface of the U937 cells after
      48 h of culture with LPS and then they became adhesive with numerous filamentous
      filopodia extruded on the cell surface, exhibiting the enhanced expression of
      CD16 and CD23, the activation cell surface markers for differentiation into
      macrophage. However, no induction or enhancement of the cell surface expression
      was observed with respect to CD11b, CD18, HLA-A, B, C, HLA-DR, DQ, DP or CD57.
      These U937 cells also acquired the ability to produce superoxide anions and to
      phagocytose the Salmonella enteritidis strain, 116-54. This phagocytosis was
      inhibited by the anti-CD11b monoclonal antibodies, but not by the anti-CD14, anti
      CD16, anti-CD18, anti-CD23, anti-HLA-A, B, C or anti-HLA-DR monoclonal
      antibodies. These findings indicate that the phagocytic activity against
      Salmonella enteritidis 116-54 induced by LPS is mediated mainly via the CD11b
      molecule, but is not associated with the increased expression of CD11b. Puromycin
      and cycloheximide, inhibitors of protein synthesis, or a divalent cation
      chelating agent, EDTA completely inhibited this phagocytic activity.
      Interestingly, EDTA was found to suppress specifically the CD11b expression on
      the U937 cells cultured with LPS. No phagocytic activity was induced when the
      U937 cells cultured with LPS were incubated at 4 degrees C, but restored to the
      control level when shifted up to 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284786
TI  - Study of HLA class II alleles by PCR oligotyping in leprosy patients from north
      India.
AB  - Host factors seem to play an important role in determining the immune response
      and the differential manifestations of lepromatous (LL) and tuberculoid (TT)
      leprosy. In order to investigate the role of immunogenetic factors in determining
      the form of leprosy, the HLA class II alleles of DRB1, DRB3, DRB5, DQA1, DQB1 and
      DPB1 were studied by a PCR oligotyping technique in 93 patients and 47 healthy
      controls. DRB1*1501 and DRB1*1502 (two of five tested subsets of the
      serologically defined DR2) accounted for 81.5% of the multibacillary patients
      (relative risk 16.3) and 60.7% of the TT patients (relative risk 5.7) compared to
      21.3% in normal, ethnically- and geographically-matched controls. The much
      stronger association of DRB1*1501 with the multibacillary form than with the TT
      type of leprosy suggests a possible role in the differential immune response to
      M. leprae antigens. DQB1*0601 was found significantly more often than in controls
      throughout the leprosy spectrum, while DQA1*0103 was most frequent in the LL
      group and DQA1*0102 was selectively increased in the borderline lepromatous (BL)
      patients. On the other hand, DRB1*0701, DQB1*0201 and DQA1*0201 were decreased in
      the multibacillary leprosy patients (MLP) compared to TT patients and controls,
      and DQB1*0503 was selectively decreased in TT patients, suggesting that these HLA
      alleles might play a role in modulating the immune response that determines the
      form of leprosy that develops in each patient.

PMID- 8284787
TI  - Genetic markers for susceptibility to endemic Brazilian pemphigus foliaceus (Fogo
      Selvagem) in Xavante Indians.

PMID- 8284788
TI  - The HLA-DP locus in systemic sclerosis--no primary association.

PMID- 8284789
TI  - Direct detection of PCR products for HLA class II typing.
AB  - Direct detection of the PCR, or DD-PCR is proposed as an efficient method for
      performing PCR assays. Following the PCR reaction, ethidium homodimer dye is
      added to the reaction mixture and read by fluorescence. The dye step circumvents
      the necessity of running reactions on agarose gel electrophoresis, which is the
      current standard. This simple modification should find wide application for
      assays utilizing the PCR reaction. Here we show the ready detection of HLA class
      II polymorphism.

PMID- 8284790
TI  - Analysis of the MHC-encoded transporters TAP1 and TAP2 in rheumatoid arthritis:
      linkage with DR4 accounts for the association with a minor TAP2 allele.

PMID- 8284791
TI  - A sixth family of HLA-A alleles defined by HLA-A*8001.

PMID- 8284792
TI  - A new DRB1 allele DRB1*1107--a combination of DRB1*11 and DRB1*03.

PMID- 8284793
TI  - Metabolic fate of methyl n-butyl ketone, methyl isobutyl ketone and their
      metabolites in mice.
AB  - The metabolic fate of methyl n-butyl ketone (MnBK) and its isomer methyl isobutyl
      ketone (MiBK) was studied in mice. The concentrations of both ketones and their
      metabolites in blood and brain were measured at different time intervals after
      their administration. The principal metabolites of MnBK were 2-hexanol (2-HOL)
      and 2,5-hexanedione (2,5-HD), while those of MiBK were 4-methyl-2-pentanol (4
      MPOL) and 4-hydroxy-4 methyl-2-pentanone (HMP). The administration of 2-hexanol
      by itself led to the appearance of both MnBK and 2,5-hexanedione which, when
      administered by itself, did not lead to the appearance of either MnBK or 2
      hexanol. The administration of 4-methyl-2-pentanol resulted in the appearance of
      MiBK and HMP. The administration of HMP did not result in the appearance of MiBK
      or 4-MPOL. These results indicate that the metabolic fate of MnBK and MiBK is
      similar to that reported in other species.

PMID- 8284795
TI  - Metabolism of benzene and trans,trans-muconaldehyde in the isolated perfused rat
      liver.
AB  - Perfusate from rat livers perfused with benzene (approximately 0.7-7 x 10(-4) M)
      or trans,trans-muconaldehyde (MUC) (10(-4) M) was extracted and analyzed by
      reverse-phase HPLC. Based on retention time and co-elution experiments, benzene
      was found to be metabolized to trans,trans-muconic acid, a urinary ring-opened
      metabolite of benzene and a major in vivo and in vitro metabolite of MUC. These
      data demonstrate that benzene ring-opening occurs in the liver. Following
      perfusion with MUC (a microsomal hematotoxic metabolite of benzene), trans,trans
      muconic acid and three other MUC metabolites were detected in the perfusate
      extract, suggesting that these metabolites would be present in the circulation
      following metabolism of MUC.

PMID- 8284794
TI  - A comparison of the efficacy of HI6 and 2-PAM against soman, tabun, sarin, and VX
      in the rabbit.
AB  - This study compared the efficacy of HI6 and 2-PAM against nerve agent (soman,
      tabun, sarin, and VX)-induced lethality in the atropinesterase-free rabbits
      pretreated with vehicle (controls) or pyridostigmine. Treatment was administered
      at signs or 2 min after agent challenge and consisted of oxime (100 mumol/kg) +
      atropine (13 mg/kg) (alone or together with diazepam). Twenty-four-h LD50 values
      were calculated for soman- and tabun-intoxicated animals, whereas 24-h survival
      was noted in animals given 10 LD50s of sarin or VX. In pyridostigmine and control
      rabbits intoxicated with soman and treated with oxime + atropine (alone or
      together with diazepam), HI6 was 3-5 times more effective than 2-PAM. In
      contrast, HI6 was less effective than 2-PAM against tabun poisoning. In
      pyridostigmine-pretreated animals exposed to tabun, efficacy was increased more
      than 3-fold when compare to tabun-challenged animals treated with atropine + HI6
      alone. Both oximes were highly effective against sarin and VX. These findings
      suggest that HI6 could replace 2-PAM as therapy for nerve agent poisoning,
      because it is superior to 2-PAM against soman, and when used in pyridostigmine
      pretreated animals, it affords excellent protection against all four nerve agents
      when used in combination with atropine (alone or together with diazepam) therapy.

PMID- 8284796
TI  - Excessive dietary selenium decreases the vitamin A storage and the enzymatic
      antioxidant defence in the liver of rats.
AB  - This study investigated the influence of selenium intake, over 8 weeks, on
      vitamin A level and on enzymatic antioxidant defence in the liver of young rats.
      Deficient animals were fed a well-balanced diet but without selenite addition;
      the Se content of this diet which originated from natural Se content of
      ingredients was 0.05 mg/kg. Controls were fed the same diet with 0.40 mg/kg added
      Se. The two other groups received high levels of Se, 2.05 or 4.05 mg/kg.
      Excessive Se intake decreased the concentrations of retinol and retinyl palmitate
      in the liver. The linear regression analysis indicated a significant (P < 0.001)
      dose-dependent vitamin A decline. As expected, Se deficit lowered glutathione
      peroxidase activity. The highest Se excess decreased the enzymatic antioxidation:
      Zn,Cu superoxide dismutase, catalase, glutathione peroxidase activities. Data
      showed that high dietary Se can sometimes enhance carcinogenesis and our results
      suggest that it is best to be cautious in administrating Se to humans with the
      aim of preventing diseases.

PMID- 8284797
TI  - A retinoic acid receptor alpha antagonist counteracts retinoid teratogenicity in
      vitro and reduced incidence and/or severity of malformations in vivo.
AB  - The role of retinoic acid receptors (RAR) in retinoid-induced teratogenesis is
      mainly unknown. The aim of the present studies was to demonstrate the effect of a
      RAR alpha antagonist on retinoid-induced teratogenic effects in vitro and in
      vivo. In micromass cultures of rat limb bud cells a RAR alpha antagonist was able
      to counteract differentiation inhibiting effects of a RAR alpha agonist. In mouse
      studies, the selective RAR alpha antagonist reduced frequency and/or severity of
      major malformations. Our observations indicate the potentiality of selective RAR
      agonists and antagonists in dissecting the function of nuclear receptors and in
      particular cases of retinoid teratogenesis, to assign to the different receptors
      a primary role in determining one or another of the multiple malformations.

PMID- 8284798
TI  - Cytotoxicity potential of surfactant mixtures evaluated by primary cultures of
      rabbit corneal epithelial cells.
AB  - The use of in vitro cytotoxicity assays as potential alternatives in assessing
      ocular irritation of surfactant mixtures was evaluated in a primary culture
      system of rabbit corneal epithelial cells. Two groups of surfactant mixtures,
      each with the same surfactant components in varying proportions, were studied.
      Cytotoxicity was determined by lactate dehydrogenase (LDH) enzyme leakage and 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) dye reduction
      in the cell culture system. There was a good correlation between the cytotoxicity
      in vitro and the reported Draize eye irritation data within each group of the
      surfactant mixtures studied.

PMID- 8284799
TI  - T cell functions are impaired by inhaled isobutyl nitrite through a T-independent
      mechanism.
AB  - Isobutyl nitrite is representative of a group of inhalants abused by male
      homosexuals and adolescents. Inhalation exposure of mice to isobutyl nitrite at
      900 ppm for 45 min per day for 14 days caused serious deficits in T cell-mediated
      immune responses. Cytotoxic T lymphocyte (CTL) activity was reduced by 36%
      following the exposure. T cell proliferative responses to mitogenic and
      allogeneic stimulation were reduced by 37% and 51%, respectively. The exposure
      did not directly alter the ability of cells to synthesize or respond to IL-2.
      Accessory cell function in facilitating T cell activation was inhibited by about
      50% following exposure to the inhalant.

PMID- 8284800
TI  - Similarities of the in vivo and in vitro effects of mercuric chloride on
      [3H]ouabain binding and potassium activation of Na+/K(+)-ATPase in isolated rat
      cerebral microvessels.
AB  - A previous study revealed that a single i.p. administration of 6 mg/kg body wt.
      of mercuric chloride (MC) durably inhibits the rat cerebral microvascular
      Na+/K(+)-ATPase activity [1]. In this study, cerebral microvessels isolated 18 h
      after MC treatment were compared to those obtained from control rats and
      subsequently treated or not treated with MC in vitro, with regard to: (a)
      [3H]ouabain binding to, and (b) K(+)-activation kinetics of, the Na+/K(+)-ATPase.
      Microvessels from MC-treated rats showed a decrease of [3H]ouabain binding down
      to 62% of the control binding, and the same degree of inhibition was attained in
      microvessels treated in vitro with 5 microM MC. Analysis of the K(+)-activation
      kinetics of Na+/K(+)-ATPase revealed a decrease of Vmax from the control value of
      13.1 to 7.67 mumol/mg/h in microvessels from MC-treated rats and 6.07 mumol/mg/h
      in microvessels treated in vitro with 5 microM MC, with no change in Km in either
      case. The similarity of the effects of in vivo and in vitro treatments suggests
      that the inhibition of the cerebromicrovascular Na+/K(+)-ATPase following in vivo
      administration of MC results from a direct interaction of Hg2+ with the enzyme.

PMID- 8284801
TI  - Toxicity of precocene II in rat hepatocyte cultures: effects of serum and culture
      time.
AB  - Omission of serum from culture medium markedly increased the toxicity of the
      cytochrome P450-activated toxin precocene II in 24-h cultures of rat hepatocytes.
      In addition, the depletion of glutathione and inhibition of cytochrome P450 in 24
      h cultures increased and decreased, respectively, the toxicity of precocene II,
      as seen in vivo. Precocene II was also toxic to 72-h cultures, although the
      effect of the serum-free medium was attenuated. However, depletion of glutathione
      and inhibition of P450 had little or no effect on the toxicity in 72-h cultures.
      Therefore, the mechanism of precocene II-induced cell death appears to change
      with time in culture.

PMID- 8284802
TI  - Trichloroacetate stimulation of liver DNA synthesis in male and female mice.
AB  - Male and female B6C3F1 mice were given trichloroacetate (TCA) by gavage for 11
      days. Livers from untreated male and female mice were unremarkable by
      histopathologic examination. In livers from mice receiving 1000 mg/kg body
      weight, the centrolobular hepatic cords showed slight changes, which included
      increased eosinophilic staining and rare apoptosis. Areas in the intermediate
      zone were noted where the architecture of the liver hepatic cords was subtly
      changed. The changes in cord architecture seemed to define nodular areas where
      cellular proliferation in animals treated with TCA had occurred. No
      histopathologic differences were noted between the livers of treated or control,
      male and female animals. Mitosis and DNA synthesis were examined using
      incorporation of [3H]thymidine into liver cells. [3H]Thymidine incorporation into
      extracted liver DNA of animals receiving TCA was significantly increased over
      controls in all treatment groups. Autoradiographic examination of liver sections
      showed that the incorporation of label in control animals was predominantly in
      peri-sinusoidal cells, whereas the majority of radiolabel incorporation in TCA
      treated animals was found in intermediate zone cells that appeared to be mature
      hepatocytes. No outstanding differences in the distribution of radiolabel in the
      liver sections from male or female mice were noted. When incorporation of
      [3H]thymidine was quantified by enumeration of labeled liver cells following
      autoradiography, incorporation of the radiolabel into hepatocytes increased with
      the dose of TCA given but there was no increase in radiolabel in peri-sinusoidal
      cells. Increased mitotic figures in intermediate zone cells resembling mature
      hepatocytes were noted in all mice treated with TCA. These results suggest that
      increased DNA synthesis and mitosis may contribute tumorigenesis by TCA.

PMID- 8284803
TI  - Analysis of sister chromatid exchange, micronucleus and chromosomal aberration
      frequencies in rodents exposed to mosquito coil smoke by inhalation route.
AB  - Mosquito coil smoke emitting from a mosquito repellent, was tested for its
      mutagenic effect in bone marrow cells from mouse and rat after 4 h acute
      inhalation exposure. Coil smoke with suspended particulate concentrations of 99
      129 mg/m3, significantly elevated the frequencies of sister chromatid exchanges
      in bone marrow cells and micronuclei in polychromatic erythrocytes. Analysis of
      chromosomal aberrations in metaphases also revealed a significantly higher
      incidence of chromosomal aberration frequency in exposed rats and mice.

PMID- 8284804
TI  - TCDD decreases brain inositol concentrations in the rat.
AB  - A single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduced significantly
      brain regional inositol levels in both the most TCDD-susceptible (Long-Evans;
      LD50 9.8 micrograms/kg) and the most TCDD-resistant (Han/Wistar; LD50 > 7200
      micrograms/kg) rat strain. The decrease emerged earlier in Long-Evans rats but
      was similar in magnitude at 8 days in both strains. There were some inconsistent
      and largely dose-independent changes in inositol-1- and inositol-4-monophosphate
      concentrations at 2 days. On day 8, a tendency towards reduced levels was seen
      especially in H/W rats. We conclude that TCDD reduces brain inositol levels
      presumably by inhibiting its synthesis by way of substrate deficit
      (hypoglycemia), but this effect does not appear to be causally related to the
      lethal action of TCDD.

PMID- 8284805
TI  - The impaired nurse--how can we help?

PMID- 8284806
TI  - Characterization of the specificity of a naturally-occurring monoclonal anti
      thymocyte autoantibody derived from an unimmunized, neonatal Balb/c mouse.
AB  - The immune repertoire of healthy unimmunized Balb/c mice contains a significant
      proportion of B lymphocytes which produce natural autoantibodies. The majority of
      these predominantly CD5+ B lymphocytes, secrete autoantibodies which react with
      conserved intracellular autoantigens such as actin, myosin and DNA. Significantly
      fewer autoreactive B lymphocytes produce natural autoantibodies reactive with
      cell surface autoantigens. In the present study, the specificity of monoclonal
      IgM kappa anti-thymocyte autoantibodies from hybridoma NMT-1 (NMT-1 maAbs),
      derived from the spleen of an unimmunized 8-day-old inbred Balb/c mouse has been
      examined. Anti-thymocyte NMT-1 maAbs reacted with cell surface molecules on 86
      87% thymocytes from mice 1-28 days of age. Thymus-restricted expression of the
      identified autoantigen was demonstrated by the lack of detectable reactivity of
      NMT-1 maAbs to cell surface molecules of Balb/c mouse splenocytes, PBLs, lymph
      node, peritoneal and bone marrow cells and tissues including brain, liver and
      kidney. Furthermore, multiparameter flow cytometry demonstrated an association
      between the expression of the cell surface autoantigen identified by NMT-1 maAbs
      and thymocyte maturation as 94-97% of the CD4+ CD8+ thymocytes expressed the
      identified autoantigen which was largely absent from CD3+ thymocytes and not
      expressed in the peripheral immune system. Tissue distribution, flow cytometry
      and competition analysis indicated differences between identified T lymphocyte
      markers, including Thy-1, and the autoantigen identified by NMT-1 maAbs in this
      study. Immunoprecipitation analysis, however, revealed that NMT-1 maAbs reacted
      with 14.5 and 18.3 kDa Thy-1-related autoantigens within Balb/c mouse thymocyte
      membrane extracts, possibly unique glycosylated forms of the Thy-1 molecule.

PMID- 8284807
TI  - Thymic stroma-derived T-cell inhibitory factor (TSTIF). 2: TSTIF acts on the
      antigen-presenting cell to inhibit antigen-stimulated T-cell proliferation.
AB  - Culture supernatant (SN) was obtained from the monolayer of the MRL104.8a thymic
      stromal cell clone. This SN alone induced proliferation of helper T-cell (Th)
      clones because it contained IL-7. However, addition of the SN to cultures of Th
      stimulated with antigen plus antigen-presenting cells (APC) resulted in potent
      inhibition of their proliferation. This suppression was ascribed to a factor
      (designated thymic stroma-derived T-cell inhibitory factor, TSTIF) that is
      contained in the MRL104.8a SN and distinct from IL-7. TSTIF affected antigen
      stimulated proliferation of both type 1 helper (Th1) and type 2 helper (Th2) T
      cell clones. The TSTIF effect was also observed by the presence of the MRL104.8a
      SN only in the initial 24 hr pre-culture during the entire course (48-72 hr) of
      antigenic stimulation. Pre-exposure of Th cells to the SN in the absence of
      Ag/APC induced their proliferation upon stimulation with Ag/APC in the next 48 hr
      cultures. However, pre-cultures of Th cells with the SN in the presence of APC
      alone (without antigen) resulted in potent inhibition of the subsequent Ag/APC
      stimulated proliferation. Interaction of TSTIF with APC but not with responding
      Th cells was further demonstrated in the following experiment: APC alone were
      exposed to the MRL104.8a SN and used for stimulation of Th that had not been
      exposed to the SN. Such an APC population exhibited a remarkably reduced capacity
      to induce antigen-stimulated Th proliferation when compared to that induced by
      freshly prepared APC or APC cultured in the absence of the MRL104.8a SN. These
      results indicate that TSTIF exerts its inhibitory effect on the antigen
      stimulated T-cell proliferation by acting on APC.

PMID- 8284808
TI  - [Intrathymic regulation of proliferation of medullary thymocytes in CBA mice].
AB  - The action of non-peptide mitogenic factor (NMF) on the following thymocytes
      populations: common cortisone-resistant (CR); cortisone-resistant cells without
      macrophages (CR-M) and mature (PNP-) thymocytes was studied. It has been shown,
      that NMF shifts the catabolism of (8-(14) C) AMP towards hypoxanthine
      accumulation as well as stimulates the (2(-14) C) Thd incorporation in DNA of
      thymocyte populations to an increasing degree when comparing CR with PNA- cells.
      The action of NMF is not mediated by macrophages. It has been concluded that
      mature PNP- population is the target for NMF.

PMID- 8284809
TI  - [Effect of varying alloxan concentration on serum levels of glucose, calcium and
      alkaline phosphatase in the rat].
AB  - Two groups of rats were injected intravenously 20 and 40 mg alloxan/kg of body
      weight respectively. It was shown that different doses of alloxan induced the
      increase of glucose concentration, activity of alkaline phosphatase and decrease
      of calcium level in the rat serum. The above changes more expressed in the groups
      of rats that received the higher dose of alloxan.

PMID- 8284810
TI  - [Paracatalytic interaction of pyruvate decarboxylase with quinones in the
      presence of an organic solvent. Formation of an active site which hinders proton
      transfer].
AB  - Inactivation kinetics of pyruvate decarboxylase under joint action of substrate
      and substituted quinones in aqueous solutions which contain 1.0-13.5 vol.% of
      methyl alcohol has been investigated. The observed inactivation rate constant of
      pyruvate decarboxylase sharply decreases with the increase of methanol
      concentration from 4 up to 7 vol.% at pH 5.8-6.4. The decrease of the rate
      constant is independent of quinone order in the kinetic inactivation equation.
      The result is that the decrease of microscopic dielectric permeability by
      interaction of methanol with hydrophobic cities of enzyme active surface hinders
      the transfer of proton at the stage which is limiting in the inactivation
      process. It is assumed that the organization of active centre of pyruvate
      decarboxylase may depend on hydrophobic contact.

PMID- 8284811
TI  - [Effect of ethanol and lipid peroxidation on testosterone biosynthesis by
      interstitial cells of rat testes].
AB  - The induction of lipid peroxidation in interstitial cells of rat testes of ADP
      Fe3+ complex results in the decrease of testosterone biosynthesis. Ethanol at 50
      mM concentration enhances the level of malonic dialdehyde and inhibits the
      steroidogenesis. Effects of alcohol and ADP-Fe3+ complex both on lipid
      peroxidation or testosterone biosynthesis are additive. This agrees with the idea
      about the mediation of ethanol effects in testes by the induction of lipid
      peroxidation.

PMID- 8284812
TI  - [Multiplicity of molecular forms of soluble carboxypeptidase-B-like enzymes in
      the cat brain].
AB  - Four forms of enzymes possessing carboxypeptidase-B-like activity have been
      detected in the soluble fraction of the cat encephalon. The first of these forms
      has molecular weight 50 kDa pH optimum is 5.0-5.6, it is four times activated by
      Co2+ ions and intensively inhibited by EDTA and reagents to sulphydryl groups.
      The other form has molecular weight 100 kDa, manifests maximum activity at pH 5.0
      5.5 and is inhibited by HgCl2. EDTA, Co2+ ions and 2-mercaptoethanol take no
      effect on its activity. Molecular weight of the third form is not less than 280
      kDa, optimum pH 5.5, is activated by Co2 ions and 2-mercaptoethanol, intensively
      inhibited by EDTA and reagents to sulfhydryl groups. The fourth form has
      molecular weight about 280 kDa, wide pH optimum with maximum at 5.5, is not
      activated by Co2+ ions and inhibited by EDTA, HgCl2, N-ethyl maleimide and 2
      mercaptoethanol.

PMID- 8284813
TI  - [Characterization of free and bound pyruvate kinase in the brain of the teleost
      fish mullet].
AB  - Activity of pyruvate kinase free and bound with the structural components that
      has been revealed in brain of red mullet. The bound form disappeared as a result
      of 1.5 hour hypoxia. The Hill coefficients for phosphoenolpyruvate and ADP of the
      both enzyme forms were about 1, but the Michaelis constants of free enzyme for
      the phosphoenolpyruvate and ADP were 2-3 times higher than that for the bound
      form. The pH-dependence of the both enzymes was similar. The free enzyme was
      studied as a result of heating probes at 45 degrees C during 15 minutes, but the
      bound form was successively activated and stabilized within this procedure. The
      ATP inhibition of the both forms was the same. Fructose-1,6-bisphosphate and
      alanine does not affect the pyruvate kinase activity. Possible mechanisms for
      regulation of kinetic properties and redistribution of pyruvate kinase between
      free and bound states are discussed.

PMID- 8284814
TI  - [Activity of the pyruvate dehydrogenase complex in Walker-256 carcinosarcoma].
AB  - Pyruvate dehydrogenase complex activity in the coarsely purified enzyme fractions
      (supernatant and mitochondrial extract) isolated from Walker-256 carcinosarcoma
      is shown to be much lower than the complex activity in the rat brain. Acetoin was
      not found in the incubation medium containing pyruvate dehydrogenase tumour
      complex. The rate of the reaction of nonoxidative formation of acetaldehyde by
      pyruvate dehydrogenase complex of the tumour was approximately five times lower
      than the rate of reaction catalyzed by the complex from the rat brain. It is
      shown that in the presence of adenine nucleotides AMP, ADP or ATP (0.5 mM) in the
      medium pyruvate: NAD+ oxidoreductase activity of the tumour complex is inhibited
      by 40-56% as compared to the control and reaction of nonoxidative decarboxylation
      of pyruvate is approximately 2 times activated. It is supposed that the
      accumulation of nonoxidative reaction products may be an essential factor for
      development and functioning of the tumour.

PMID- 8284815
TI  - [Structural similarity of the active sites of major histocompatibility complex
      class I proteins and ubiquitin].
AB  - With the help of a new method of protein primary structures analysis, i.e. CAACRA
      (comparative amino acid codon root analysis) a marked structural similarity of
      the MHC class I protein active sites and ubiquitin alpha-helix has been revealed.
      Using the CAACRA a periodicity of ubiquitin primary structure has been shown.
      Ubiquitin molecule consists of 4 repeat units.

PMID- 8284816
TI  - [Enzymes of ethanol metabolism in the liver of rats with varying alcohol
      motivation in acute alcoholization].
AB  - Alcohol dehydrogenase (ADH) activity does not change in ethanol-preferring rats
      (EP receiving ethanol injection in a dose of 2.5 g/kg; an increase of the dose to
      4.5 g/kg leads to a descent of activity 60 min later. Enhancement of the reverse
      reaction activity 120 min after injection of ethanol both doses probably induce
      faster metabolism of acetylanhydride and thus absence of the adverse ethanol
      action in these animals. An increase of activity of NAD(+)- and NADP(+)-dependent
      isoforms of ALDH-II 60 min after their injection in a dose of 2.5 and 4.5 g/kg
      also contributes to this effect. Synchronous changes both in direct and reverse
      ADH reactions in water-preferring (WP) rats with 2.5 g/kg ethanol injection were
      observed: the activity increase 30 min later followed by normalization at the
      60th min and a repeated increase 120 min later; a dose of 4.5 g/kg induced an
      increase of only direct ADH reaction activity at the 30th and 60th min. The liver
      mitochondria ALDH-I of WP were practically unsusceptible to ethanol in a dose of
      2.5 and 4.5 g/kg. Activity of NAD(+)-dependent ALDH-II mitochondria decreased
      with 2.5 g/kg at the 30th and 60th min, respectively. Yet an increase in activity
      of isoforms in microsomes was observed. ADH activity in short-sleeping (SS) rats
      does not change both at 2.5 and at 4.5 g/kg doses. More intensive ethanol
      metabolism in these rats is probably connected with increased activity of MEOS
      and catalase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284817
TI  - [Activity of neutrophil proteinase in rat skeletal muscles after muscle
      activity].
AB  - Neutrophil proteinases have been studied for their activity in the rat skeletal
      muscles after muscular activity using antiserum to neutrophils. The increase of
      proteolytic activity after physical load partially determined by neutrophil
      proteinases in the skeletal muscles is shown.

PMID- 8284818
TI  - [Biochemical markers of muscle tissue during regenerative processes in newts and
      annelid worms].
AB  - The biochemical markers of muscle tissue (creatine- and pyruvate-kinase
      activities and myosin chains maintenance) have been studied at different stages
      of regeneration process in newt and annelid worms. The enzymes' activity and
      myosin chains maintenance decrease at the stage of dedifferentiation and return
      to the standard under redifferentiation of regenerating sites. In some cases the
      increase of the enzyme activity during redifferentiation is remarked. The results
      obtained are compared with data about changes of the biochemical markers during
      embryogenesis and post-embryogenesis. The community of the mechanisms of
      differentiation and embryogenesis is discussed.

PMID- 8284819
TI  - [Effect of nitrobenzenes on methemoglobin formation and activity of antioxidative
      enzymes in mouse erythrocytes].
AB  - The mice intoxication with intraperitoneal introduction of 1,3,5-trinitrobenzene
      and 2,4,6-trinitrotoluene causes an increase of methemoglobin and a decrease of
      glutathione level. But intoxication by polynitrobenzenes exerts no effect on the
      total level of SH-groups. A small increase in total activity of dehydrogenases of
      the pentose phosphate way in response to 2,4,6-trinitrotoluene intoxication is
      also revealed. The level of both lipid peroxidation, superoxide dismutase and
      catalase activity is not influenced by 2,4,6-trinitrotoluene and 1,3,5
      trinitrobenzene.

PMID- 8284820
TI  - [Effect of fluorine in drinking water of varying hardness on protein-mineral
      metabolism of mineralized tissues of rats maintained on a sugar diet].
AB  - Variations of mineral and protein metabolism in calcified tissues were studied
      using 32P, 45Ca and 35S methionine in the rats on sugar diet and water of
      different hardness with F and without it. Hard drinking water without F like soft
      water and water of medium hardness with F affect metabolism in mineralized
      tissues preventing the development of carious process. Incorporation of 32P and
      45Ca to mineralized tissues, specific radioactivity of 32P and 35S methionine of
      tooth and bone proteins are lower in rats which drank soft water without F. These
      parameters increase in rats which received hard water without F almost to the
      level of animals which received water with F. Ways of the effect of Ca2+ Mg2+ and
      F on protein and mineral metabolism of calcified tissues of rats on sugar diet
      (including proteins (osteo-induced, etc., which initiate mineralization) and
      enzymes are considered.

PMID- 8284821
TI  - [Degree of leucine utilization in the provision of substrate for lipid synthesis
      in animal tissues in vivo].
AB  - Radioactivity of lipids synthesized in the encephalon, liver kidneys, lungs,
      pancreas, stomach mucosa, duodenum, heart, skeletal muscle, fat tissue and rat
      skin 2h after intraperitoneal administration of [U-14C] leucin is 0.38-19.3% of
      protein radioactivity, 31.2-615.3% of radioactivity of lipids synthesized in the
      mentioned organs and tissues of rats whom [U-14C] glucose was administered. CO2
      radioactivity in rats released with the expired air in 1.5% of medium
      radioactivity of proteins in the studied organs and tissues, 19.5% of
      radioactivity of 14CO2 released with the expired air in rats who were
      administered [U-14C] glucose.

PMID- 8284822
TI  - [Lipid composition and fertility of human ejaculate].
AB  - The morpho-functional indexes of ejaculates from 35 healthy and 145 infertile men
      were studied. The depression of functional sperm activity was found in the
      majority of infertile men. Phospholipid analysis of whole ejaculates from 12
      healthy and 35 infertile subjects was performed. It was shown that inorganic
      phosphorus of total phospholipids decreased in ejaculates of men with secretory
      infertility. Lyso-phosphatidyl choline (LPC) was not detected in ejaculates of
      men with relative infertility. The amount of lyso-phosphatidyl ethanolamine (lyso
      PE) and sphingomyelin in whole ejaculates of those patients decreased. The levels
      of LPC and lyso-PE decreased in ejaculates of persons with associated
      infertility. The level of phosphatidyl inositol, LPC and PE decreased in
      ejaculates of men with secretory infertility. The gas-lipid chromatography
      analysis of fatty acids composition of whole ejaculates of the infertile men
      showed significant changes in quantity of fatty acids. The quantity of
      docosahexaenoic acid in ejaculates of infertile men decreased and positively
      correlated with motility of spermatozoa.

PMID- 8284823
TI  - [Development of a highly efficient method for separating bee venom components].
AB  - Factors preventing complete separation of melittin and phospholipase A2 under
      fractionation of the bee venom were studied. The methods of electrophoresis in
      PAAG, gel-filtration, ion-exchange and reverse-phase chromatography were used to
      show that the intermolecular interactions of suppositionally hydrophobic
      character prevent from complete separation of melittin and phospholipase A2.
      Conditions and methods are chosen which permit isolating melittin and
      phospholipase in a pure form.

PMID- 8284824
TI  - [Phospholipids of human spermatozoa and their role in ensuring fertility].
AB  - The phospholipid composition of spermatozoa in healthy subjects (n = 13) and
      infertile men (n = 38) was studied. The level of inorganic phosphorus of total
      phospholipids decreased in spermatozoa of infertile men (relative and excretory
      infertility). It was found that the phosphatidyl ethanolamine amount in
      spermatozoa of infertile men fell. The level of phosphatidyl serine had certain
      tendency to decrease as well. Lyso-phosphatidyl serine was detected in some
      samples of infertile spermatozoa. Correlation between the amount of spermatozoa,
      its motility, vitality etc. and content of some phospholipids was found.

PMID- 8284825
TI  - [Phospholipids of human seminal plasma and their role in ensuring fertility].
AB  - The phospholipid composition of seminal plasma from health (n = 13) and infertile
      men (n = 49) was studied. A significant decrease of lyso-phosphatidyl choline and
      lyso-phosphatidyl serine levels in seminal plasma of men with relative
      infertility was shown. Two-fold enhancement of phosphatidyl serine in seminal
      plasma of men with excretory infertility was found. A significant decrease of
      lyso-phosphatidyl choline in men with associated infertility was determined. An
      essential decrease of lyso-phosphatidyl serine and lyso-phosphatidyl choline in
      men with secretory infertility were shown. The level of phospholipids correlated
      with some morphological and functional characteristics of ejaculate.

PMID- 8284826
TI  - [NADH as a substrate of enzymatic lipid peroxidation].
AB  - The existence of enzymatic NADH-dependent peroxidation of lipids has been
      established. Some its characteristics in comparison with nonenzymatic ascorbate
      dependent and enzymatic NADPH-dependent lipid peroxidation have been found. Some
      reactions of enzymatic peroxidation of lipids (NADPH- and NADH-dependent) in
      contrast to nonenzymatic (ascorbate-dependent), is not inhibited by the electron
      carriers (methylene blue and vikasol). This part of lipid peroxidation is not
      affected by hypoxia and combined effect of hypoxia as well as the action of
      carbon oxide (II) both separate and in combination with the electron carriers.

PMID- 8284827
TI  - [Comparative characteristics of color reactions to ecdysteroids].
AB  - The colour reactions used to determine sterols have been compared to find most
      sensitive method of quantitative determination of ecdysteroids. It is shown that
      the Liberman-Burchard reaction is most sensitive to most ecdysteroids, while the
      Chugaev reaction is most specific.

PMID- 8284828
TI  - [Metabolism and catabolism to CO2 of [14C] gamma-aminobutyric acid conjugates
      with pyridoxal phosphate, nicotinate and biotin].
AB  - Pharmacokinetics and catabolism to CO2 in the mice organism and metabolic
      transformation by the tissues homogenates of [1-14C] GABA and its conjugates with
      nicotinate, pyridoxal phosphate and biotin have been studied. The permeability of
      nicotinoyl-GABA through the hemato-encephalic barrier was 10 times as much as the
      corresponding value for GABA and its conjugates with other vitamins. PLP-GABA is
      eliminated more rapidly from the brain in comparison with GABA, biotinyl-GABA is
      retained to a higher degree in kidneys, the entero-hepatic recycling takes place
      more actively for nicotinoyl-GABA. The latter, in contrast to biotinyl-GABA,
      remains unaffected by the liver, intestine mucose membrane and brain proteases
      and is catabolized to CO2 to a considerably lower extent as compared with GABA,
      perhaps due to the intestine bacterial microflora.

PMID- 8284829
TI  - [N-demethylation and denitrosation activity of the rat liver, thymus lymphocytes
      and spleen after exposure to simazine and sodium nitrite].
AB  - Simazine and NaNO2 have been studied for their effect on cytochrome P-450-binding
      N-demethylation and denitrosation activity in the rat liver and lymphocytes in
      the subchronic (two-month-long) experiment. N-demethylation in lymphocytes of the
      thymus and spleen was higher than in the liver; denitrosation in the lymphocytes
      was not observed. Effects of simazine and NaNO2 being injected separately in most
      of cases have different directions. Combined injection of these substances
      exceeded the total effect.

PMID- 8284830
TI  - [Effect of pyrazole on the activity of acetaldehyde-producing enzymes in the
      liver].
AB  - Influence of pyrazole on the endogenous ethanol level and activities of
      acetaldehyde-producing enzymes was investigated. Drastic enhancement of the
      endogenous ethanol level in the blood and tissues was accompanied by an
      insignificant increase of phosphoethanolamine lyase activity, while activity of
      threonine aldolase and pyruvate dehydrogenase was unchanged.

PMID- 8284831
TI  - Interstitial cystitis. A patient's perspective.
AB  - Interstitial cystitis is a debilitating bladder disorder that affects up to
      450,000 people in the United States, 90% of whom are women. Confusion in defining
      and understanding interstitial cystitis has resulted in the failure to diagnose
      and treat thousands of afflicted patients, committing them to a life of
      intractable pain. Even with diagnosis, there are no uniformly effective
      treatments. It is extremely important that these patients have the understanding
      and support of the medical community, and they should develop a constructive and
      effective relationship with their physician and other urologic caregivers.

PMID- 8284832
TI  - Nalmefene in the treatment of interstitial cystitis.
AB  - Nalmefene is a new narcotic antagonist that is structurally similar to naloxone
      and naltrexone. The drug is a long-acting oral agent that is a pure opiate
      antagonist without agonist activity. Nalmefene appears to be a safe and effective
      compound for the treatment of interstitial cystitis. Longer-term studies and
      Phase III randomized trials need to be completed to substantiate these
      encouraging findings.

PMID- 8284833
TI  - Calcium channel antagonists in the treatment of interstitial cystitis.
AB  - The calcium channel antagonist nifedipine has shown efficacy in the treatment of
      interstitial cystitis and the urethral syndrome. The optimal daily dose of
      nifedipine can be determined with the use of a nifedipine titration test. To
      complete the repair of damaged bladder and/or urethral mucosa, nifedipine therapy
      should be used for a minimum of 3 months. Patients who do not respond well to
      nifedipine are those with the pelvic floor muscle spasm syndrome variant of
      interstitial cystitis.

PMID- 8284834
TI  - Hydroxyzine in the treatment of interstitial cystitis.
AB  - Hydroxyzine is a piperazine, tricyclic, H1-receptor antagonist with unique
      properties, especially the inhibition of mast cell and neuronal secretion.
      Preliminary results indicate is has an unusual ability to reduce interstitial
      cystitis symptoms. The long history, lack of major side effects, wide
      availability, low cost, and apparent effectiveness of hydroxyzine compel
      presentation of these preliminary results.

PMID- 8284835
TI  - Self-care regimens for patients with interstitial cystitis.
AB  - For those who suffer from interstitial cystitis, living with the condition is a
      challenge that requires creativity, patience, determination, and a sound set of
      coping mechanisms. Because of the high percentage of gynecologic and systemic
      manifestations of interstitial cystitis, a customized treatment regimen is often
      necessary to achieve the therapeutic goal of a remission in symptoms. Treatment
      philosophies should be based on the proposed causative mechanisms, and a
      multimodality approach to therapy is usually successful. Self-care regimens give
      the patient a sense of control by active participation in treatment, which often
      improves coping mechanisms. Treatment of the sequelae of chronic pain (anxiety
      and depression) often improves response to overall therapy. Remission is the
      goal, coping is the key, and creativity opens the door to treating this most
      perplexing of conditions.

PMID- 8284836
TI  - Transcutaneous electrical nerve stimulation in classic and nonulcer interstitial
      cystitis.
AB  - Long-term treatment of interstitial cystitis by transcutaneous electrical
      stimulation provides a conservative means of bringing the disease to remission.
      The overall results are better in the classic than in the nonulcer subtype of
      interstitial cystitis. These findings are considered in relation to the role of
      neutral factors in the disease.

PMID- 8284837
TI  - Laser therapy for interstitial cystitis.
AB  - Laser treatment for interstitial cystitis patients should be limited to those who
      are positively diagnosed and have failed more conservative forms of therapy. The
      results are not as beneficial for patients with intractable pain but show only
      signs of glomerulation. When the laser is used within the proper power settings
      and the amount of energy applied during any one operative procedure is limited,
      the treatment is safe and can be very beneficial.

PMID- 8284838
TI  - Surgical management of interstitial cystitis.
AB  - For most urologists the decision to operate on a patient with interstitial
      cystitis is made with extreme caution. The knowledge that this is a nonmalignant
      disease, that it poses little risk to overall health (although most patients
      would differ with this assertion), and that surgical intervention may be
      accompanied by additional complications has relegated open surgical procedures to
      last on the list of treatments for interstitial cystitis. This reluctance to
      operate until late in the course of the disease is clearly unsatisfactory. If a
      successful surgical procedure can performed, it ought to be employed early in the
      course of the patient's management and not withheld after the unfortunate patient
      has been subjected to a host of unsatisfactory conservative treatments. There is
      a need for balance between timidity and surgical aggression in the management of
      this dreadful condition. There is a need to identify the appropriate patients for
      surgical treatment and to select the most successful procedure. We should not
      expect to have to move through a series of different procedures for each patient,
      but rather select the right one the first time. There is an obvious need for a
      better understanding of the precise cause and pathogenesis of the condition so
      that alternative forms of treatment may be investigated. Surgery can provide
      significant relief for many patients with incapacitating symptoms. Cystectomy,
      either supratrigonal or total, is best reserved for those patients with markedly
      reduced bladder capacities.

PMID- 8284839
TI  - Interstitial cystitis. Current and future approaches to diagnosis and treatment.
AB  - Both the patient and physician must understand that there is no single cure for
      interstitial cystitis, nor is there a single treatment that is effective in
      reducing symptoms for every patient. Most patients, however, can benefit from one
      treatment or another, or from a combination of treatments. The author's general
      philosophy about the treatment of interstitial cystitis is described, and other
      theoretical modalities of treatment are discussed.

PMID- 8284840
TI  - Current findings and future research avenues in the study of interstitial
      cystitis.
AB  - This article reports the progress made in the last several years of
      investigations into possible pathogenic processes that lead to the development of
      interstitial cystitis. The evidence presented here asserts that bladder mucin is
      functionally intact in interstitial cystitis and that the permeability of the
      afflicted patient's bladder is not greater than normal.

PMID- 8284841
TI  - Collagen injection therapy for urinary incontinence.
AB  - The goal of treatment in patients with ISD is to allow for coaptation of the
      urethral mucosa without obstruction. Urodynamically this means that the pressure
      necessary to open the urethra (leak point pressure) is increased but no
      appreciable change occurs in the closure pressure of the urethra. Periurethral
      injections have the potential to accomplish this need. Contigen appears
      efficacious and safe in the properly chosen patient. The cross-linking of the
      bovine collagen has enhanced the durability of the substance when injected and
      reduced the potential to produce local immune-type reactions. None of the
      patients in the multicenter trial (many of whom have been followed for more than
      5 years) have had an adverse event related to immunogenicity. The technical
      aspects of the actual injection process are easily learned, and no special
      equipment is needed. More important than technique is patient selection. The best
      results are attained in those patients who do not have detrusor problems, have an
      adequate bladder capacity, and have minimal anatomic abnormality (urethral
      hypermobility). Because injection of Contigen can usually be done with local
      anesthesia alone, a significant number of patients who are not acceptable
      candidates for open surgical procedures (slings and artificial sphincters) may
      benefit from this treatment. It is anticipated that Contigen will be a valuable
      adjunct in the management of both adult and pediatric incontinence problems.

PMID- 8284842
TI  - The etiology of interstitial cystitis.
AB  - The cause of interstitial cystitis remains unknown. Potential causes including
      infection, vascular alterations, psychological aberrations, bladder surface
      alterations, toxic agents, neurologic disorders, and autoimmune responses have
      been investigated. To date, no compelling evidence for any hypothesized cause is
      available. Recently, several animal models have been described that may provide a
      basis for fundamental biologic studies that may aid in answering this important
      question.

PMID- 8284843
TI  - Interstitial cystitis as an infectious disease.
AB  - In the author's opinion, infection has not been properly ruled out as a factor in
      the development of interstitial cystitis. Dismissing infection as a cause would
      require special techniques to search for microorganisms not only in urine but
      also in bladder tissue. Infection is not necessarily exclusive of other theories
      concerning the pathogenesis of interstitial cystitis, such as autoimmunity or
      increased bladder permeability.

PMID- 8284844
TI  - The role of the mast cell in interstitial cystitis.
AB  - The bladder mast cell contains many granules, each of which can secrete many
      vasoactive and nociceptive molecules. A number of conditions, such as extreme
      cold, drugs, neuropeptides, stress, trauma, and toxins, can trigger the mast cell
      to secrete some of its contents; they, in turn, can sensitize sensory neurons,
      which can further activate mast cells by releasing neurotransmitters or
      neuropeptides. Additionally, the mast cell can directly cause vasodilation and
      bladder mucosa damage while also attracting inflammatory cells, thus causing many
      of the problems seen in interstitial cystitis. The mast cell appears to be
      involved in the pathogenesis of interstitial cystitis. Although it is not
      pathognomonic of the disease, mastocytosis does occur in a significant subset of
      interstitial cystitis patients. Because interstitial cystitis is now regarded as
      a syndrome caused by multiple factors, it is conceivable that one cause of
      interstitial cystitis is associated with bladder mastocytosis and mast cell
      activation. The fact that mast cells are also increased in patients with
      transitional cell carcinoma of the bladder does not diminish the importance of
      mastocytosis in interstitial cystitis, because the mast cells are not activated
      in carcinoma but are activated in interstitial cystitis. Perhaps the common
      strand between these two bladder diseases is the putative allergens/carcinogens
      in bladder urine that breach the protective lining of the bladder and then elicit
      an immune response in the bladder wall. Furthermore, the majority of patients
      with a history of bladder tumors receive multiple courses of intravesical
      chemotherapy (such as thiotepa) or immunotherapy (bacille Calmette-Guerin), and
      it is possible that these agents damage the bladder lining or provoke an
      inflammation in the bladder wall. The theory of a defective/deficient bladder
      glycosaminoglycan layer in interstitial cystitis is also consonant with this
      putative chain of events in the pathogenesis of interstitial cystitis. Thus these
      two theories interstitial cystitis causation--a glycosaminoglycan deficiency and
      bladder mastocytosis--may well operate in concert to cause bladder inflammation
      and the symptoms of interstitial cystitis. Clinicians may be at a distinct
      disadvantage because they are faced with a multitude of potential mast cell
      triggers and numerous mediators secreted. It may, therefore, be advisable to
      block or inhibit the mast cell from responding to many of these various stimuli.
      Specific mast cell mediators should be assayed as possible diagnostic tools, and
      potential mast cell inhibitors should be tried under controlled conditions to
      determine the extent of therapeutic benefit.

PMID- 8284845
TI  - Pathology of interstitial cystitis.
AB  - Morphologic changes, including light microscopy and ultrastructural, immunologic,
      and immunohistochemical findings in interstitial cystitis are described. The
      results indicate that biopsies are useful as an aid in the diagnosis of
      interstitial cystitis.

PMID- 8284846
TI  - Diagnosis of interstitial cystitis.
AB  - The diagnosis of interstitial cystitis is best based on the techniques necessary
      to elicit the criteria established at the conferences of the National Institute
      of Arthritis, Diabetes, Digestive, and Kidney Diseases (NIDDK). Essentially, this
      requires a thorough patient history, urodynamic evaluation, and cystoscopy
      carried out under anesthesia with hydrodistention of the bladder and bladder
      biopsy. Diagnosis of interstitial cystitis is tightly linked to its definition,
      and until the latter is crystal clear, the former will continue to be murky.

PMID- 8284847
TI  - Measurement of symptoms of interstitial cystitis. A pilot study.
AB  - The existence of a reliable and valid measure of interstitial cystitis symptoms
      would assist with diagnosis and the evaluation of treatment effectiveness. The
      purpose of this article is to report development of a scale to measure symptoms
      of interstitial cystitis. Data concerning the evidence of content and construct
      validity, as well as reliability, is provided. The findings suggest that this
      scale accurately measures the symptoms of interstitial cystitis.

PMID- 8284848
TI  - Epidemiology of interstitial cystitis.
AB  - This article concerns a survey conducted to determine the origin and history of
      interstitial cystitis. Information was elicited from 565 patients on
      demographics, risk factors symptoms, pain, and psychological factors. All those
      surveyed satisfied the National Institute of Arthritis, Diabetes, Digestive, and
      Kidney Diseases (NIDDK) criteria for interstitial cystitis and have been
      diagnosed as having the disorder. Comparison of risk factors was made with a
      control group of 171 individuals, consisting of healthy individuals over 18 years
      old and of adults attending urology clinics for bladder disorders unrelated to
      interstitial cystitis.

PMID- 8284849
TI  - Standard intravesical therapies for interstitial cystitis.
AB  - The treatment of interstitial cystitis is difficult and at time frustrating--both
      for the patient and for the physician. Treatment is hampered by the lack of a
      clear understanding of its pathophysiology, which makes it difficult to
      objectively assess disease severity and/or progression. Intravesical therapy
      appears to be the most successful approach to the relief of symptoms. Clearly,
      there are drawbacks to intravesical therapy, particularly Clorpactin lavage.
      Responses to intravesical lavage are variable in duration, unpredictable, and
      unamenable to objective measurement. Multiple treatments are frequently needed,
      as with DMSO, and multiple anesthetics may be required for Clorpactin therapy.
      There have been no double-blind, placebo-controlled studies comparing the
      mainstays--Clorpactin and DMSO--of intravesical treatment. It is hoped that
      current research into the pathogenesis and causation of interstitial cystitis
      will lead to an improved understanding of this disease or syndrome. The
      introduction of newer, more specific intravesical therapies will surely follow
      such advances.

PMID- 8284850
TI  - Dimethyl sulfone (DMSO2) in the treatment of interstitial cystitis.
AB  - DMSO2 is one alternative for treating interstitial cystitis. Research with this
      compound is very limited, but side effects have been negligible. The drug may
      hold promise for interstitial cystitis patients, as well as those suffering from
      painful bladder (urethral) syndrome.

PMID- 8284851
TI  - Amitriptyline in the treatment of interstitial cystitis.
AB  - Limited data and an accumulated body of anecdotal experience with the tricyclic
      class of antidepressants suggest that this group of drugs (especially
      amitriptyline) may be an effective treatment modality in nonulcerative
      interstitial cystitis. Both the ease of administration and the relatively rapid
      onset of relief make these types of drugs appropriate to consider for first-line
      therapy after bladder distention has failed.

PMID- 8284852
TI  - [Graduate and Continuing Education Commission of German Urologists].

PMID- 8284853
TI  - [Operable diseases of the adrenal gland].

PMID- 8284854
TI  - [Synchronous growth of a mixed mesodermal tumor and an adenocarcinoma of the
      urinary bladder].
AB  - The case of synchronous growth of a mesodermal mixed tumour and an adenocarcinoma
      in the bladder is presented. This is a rare phenomenon. Mesodermal mixed tumours
      are malignancies with both epithelial (carcinoma) and mesenchymal (sarcoma)
      differentiation. The term carcinosarcoma is frequently used in the literature. In
      most cases the prognosis of mesodermal mixed tumours, which depends mainly on the
      high rate of local recurrences, is poor. Therefore, cystectomy with suprapubic
      urinary diversion is the treatment of choice. However, results reported in the
      literature show that transurethral resection of the tumour may be adequate when
      there is only superficial growth of mesodermal mixed tumours. Short follow-up
      intervals are absolutely essential for patients treated this way.

PMID- 8284855
TI  - [The androgen receptor. New aspects in intersexuality patients].
AB  - Androgen resistance is thought to vary phenotypically from a normal female to an
      infertile male. At the functional level a variety of defects have been detected
      in cultured skin fibroblasts in these patients. Since the isolation and cloning
      of the 5 alpha-reductase and the androgen receptor gene, several new disorders
      have been characterized at the molecular level, including major gene
      rearrangements, deletions and defects in RNA splicing, and single amino acid
      substitutions. These studies have provided insight into the spectrum of
      mechanisms that can alter receptor function and serve to increase our
      understanding of the etiology in patients with androgen resistance.

PMID- 8284856
TI  - [Effectiveness and safety of cavernous body auto-injection therapy with
      papaverine/phentolamine. Study group].
AB  - A multicenter long-term study at 13 urologic clinics in Germany and Austria
      tested the efficacy and safety of a papaverine (15 mg/ml) and phentolamine (0.5
      mg/ml) mixture (ANDROSKAT) in achievement of pharmacologically aided erection.
      The study population of 157 men with chronic erectile dysfunction received a
      total of 559 injections administered by physicians, to establish the individual
      minimal dose of the mixture needed by each patient for a rigid erection. Rigidity
      sufficient for intercourse was achieved by 94% of these men. In the second phase
      of the study, 92 men administered a total of 4717 self-injections (mean 51.2, SD
      7.7), with an average follow-up of 14 months. The mean therapeutic dose was 1.02
      ml (SD 0.72). The latency time to full erection averaged 10.3 min (SD 5.5). The
      average duration of the erection induced was 67.1 min (SD 40.8, min. 11.2, max.
      236). Sexual intercourse, orgasm and ejaculation were reported following 90%, 88%
      and 86%, respectively, of all injections. In the initial diagnostic phase,
      prolonged erections were seen in 13 patients (3%) and minor bruises at the
      injection site in 12 men. Side effects of self-injection during home therapy were
      pain (1.2%), haematoma (2.6%) and prolonged erection (0.9%). We conclude that
      self-injection with a combination of papaverine and phentolamine is an efficient
      and safe long-term treatment for erectile dysfunction.

PMID- 8284857
TI  - [Ultrastructural studies of the ileum neobladder].
AB  - Four patients had cold biopsies of the ileal mucosa 15-40 months after bladder
      substitution with an ileal neobladder. We used electron optical systems
      encompassing scanning electron microscopy and transmission electron microscopy
      for ultrastructural evaluation of the specimen. The changes observed did not vary
      markedly from patient to patient. In all biopsies the number of normal intestinal
      mucosa cells as well as mitochondrial density and number of microvilli was
      significantly reduced. In contrast the density of goblet cells was similar to
      that found in normal ileal tissue. These findings confirm the clinical
      observation that, on long-term follow-up, patients with an ileal neobladder show
      a decrease in urinary resorption via the ileal mucosa, whereas mucus secretion
      tends to be constant.

PMID- 8284858
TI  - [The biofragmentable Valtrac ring--a reliable concept for enteral anastomosis?].
AB  - In a retrospective investigation, 54 patients with 55 enteric anastomoses
      performed with the new biofragmentable Valtrac ring were examined. In 45 patients
      with disease of the colon partial resection of the large bowel had been
      performed. In 9 patients undergoing urinary diversion an end-to-end ileostomy was
      performed. The most important advantage of this device is that its use is
      achieved by way of a safe and quick technique which is easy to learn. Bowel
      stenosis, bleeding and other complications independent of anastomotic technique,
      such as wound infection, were no more frequent than after conventional suture
      anastomosis. In 3 patients an anastomotic leakage appeared. In 1 of these cases
      conservative management for a colocutaneous fistula was successful, but the other
      2 patients had to undergo a second operation. In our opinion, the Valtrac system
      offers a convincing and reproducible alternative to conventional anastomotic
      techniques and it is easy to learn how to apply it.

PMID- 8284859
TI  - [Therapy of prostate abscess by employing pigtail drainage with transrectal
      ultrasound control].
AB  - Prostatic abscess is a rare but often severe disease. In most cases diagnosis is
      difficult. The best diagnostic tool is transrectal ultrasound, which depicts
      prostatic abscess very clearly. The therapy of choice to date is surgery, usually
      transurethral resection. At the Department of Urology of the University of Kiel
      we have employed another form of treatment, namely perineal drainage of the
      abscess with a pigtail tube under transrectal ultrasound guidance. This method is
      expected to be particularly advantageous in younger patients, for whom
      transurethral resection may cause problems. Five patients aged 24-71 years have
      been treated in this manner so far.

PMID- 8284860
TI  - [Treatment of ureteral calculi in bone coverage using in situ ESWL in prone
      position].
AB  - From January 1988 to February 1992, a total of 26 patients with calculi in the
      middle third of the ureter underwent primary in situ ESWL in the prone position.
      All treatments were performed in sedoanalgesia using the Dornier HM 3
      lithotriptor. During and after ESWL in the prone position, severe complications
      did not occur. Of the 26 patients, 10 (38%) were treated by a single application
      of ESWL. No auxiliary measures were necessary, and they became stone-free within
      3 months following treatment. In another 9 patients (35%) auxiliary measures were
      required for visualization of radiolucent calculi or to relieve a urinary tract
      obstruction with incipient septicemia. All these auxiliary measures could be
      performed in sedoanalgesia. In the remaining 7 patients (27%), in whom stone
      disintegration following ESWL was incomplete, ureteroscopic lithotripsy
      techniques had to be applied. One of these 7 patients had to undergo an
      additional open operative procedure. The results of the present study demonstrate
      that a majority of patients with calculi in the middle portion of the ureter can
      become stone-free without invasive lithotripsy techniques following ESWL in the
      prone position, if necessary plus auxiliary measures, in sedoanalgesia. From
      these results it can be concluded that primary ESWL in the prone position should
      be considered for patients with calculi in the middle third of the ureter before
      invasive lithotripsy techniques are applied.

PMID- 8284861
TI  - [Electronic data processing in urologic clinics. Results of a survey. Electronic
      Data Processing in Urology Group of the Graduate and Continuing Education
      Commission of German Urologists].
AB  - Computer equipment in Departments of Urology in Germany was evaluated by a nation
      wide questionnaire. One hundred and fifty-three questionnaires were returned with
      detailed information on computer hardware, software and applications in Urology.
      Most departments were equipped with at least one computer. Computer equipment
      varied considerably among the participants including both stand alone personal
      computers (PCs) and local area networks (LANs) with several PCs connected by
      cable. Typically, PCs were IBM-compatible and ran the MS-DOS operating system
      Word processing and related applications were the most frequently mentioned
      computer tasks in urology. In some departments computers are also used in
      research for production of databases and graphics and for statistical
      applications. When computers were used for documentation of therapy and/or
      medical records, software was often custom-made according to the department's
      specific needs. In the future, more computers will be needed in departments of
      urology, because medical records will have to meet higher standards of
      documentation.

PMID- 8284862
TI  - [An unusual case of ureter ligation after abdominal hysterectomy].
AB  - Iatrogenic ureteral lesion is a severe complication in gynecological surgery. We
      present a case in which the obstruction led to fornix rupture, urine
      extravasation and urinary ascites. The problematic diagnostic pathway is
      emphasized.

PMID- 8284863
TI  - [Malignant pheochromocytoma of the urinary bladder. Case report and review of the
      literature].
AB  - Iatrogenic ureteral lesion is a severe complication in gynecological surgery. We
      present a case in which the obstruction led to fornix rupture, urine
      extravasation and urinary ascites. The problematic diagnostic pathway is
      emphasized.

PMID- 8284864
TI  - [Pneumoscrotum. Case report and review of the literature].
AB  - The rare case of a pneumopenis and pneumoscrotum after a thoracic operation is
      reported. Two subtypes--pneumatocele and subcutaneous emphysema of the scrotum-
      are differentiated on the basis of anatomy. The cases reported in the literature
      so far are reviewed. A therapeutic regimen is recommended.

PMID- 8284865
TI  - Catheterization of edematous uncircumcised penis.
AB  - Catheterization of a grossly edematous uncircumcised penis can be challenging if
      the prepuce cannot be retracted. Herein is described a technique in which an
      anoscope is used to visualize the meatus and facilitate placement of a Foley
      catheter. This simple technique can obviate the need for cystoscopy or suprapubic
      cystotomy.

PMID- 8284866
TI  - Alkalinization of local anesthesia with sodium bicarbonate--preferred method of
      local anesthesia.
AB  - Effective anesthetic techniques include local anesthetic infiltration with or
      without sedation and general anesthesia. Local anesthesia is a safe and effective
      anesthetic technique, that when performed properly is applicable to many
      outpatient urologic procedures. We have found that the pain usually associated
      with intradermal injection of lidocaine is attenuated by the addition of sodium
      bicarbonate.

PMID- 8284867
TI  - Renal cell carcinoma in the presence of adult polycystic kidney disease.
AB  - A case of autosomal dominant polycystic kidney disease associated with widely
      metastatic renal cell carcinoma is reported. The patient had presented with
      pneumothorax, weight loss, leukocytosis, lytic bone lesions, and hypercalcemia.
      Despite intensive diagnostic search for a neoplasm, no firm evidence of
      malignancy was found. However, at the autopsy, widely metastatic, papillary renal
      cell carcinoma was found originating in the left kidney. Many metastases showed
      central necrosis mimicking small cysts.

PMID- 8284868
TI  - Perirenal liposarcoma containing extramedullary hematopoiesis associated with
      renal cell carcinoma.
AB  - We present the first reported case of a perirenal well-differentiated liposarcoma
      containing extramedullary hematopoiesis associated with an ipsilateral T2N0M0
      renal cell carcinoma. This patient, a seventy-one-year-old white male, had no
      known hematologic disorder and on preoperative evaluation had similar
      radiographic findings identified within the contralateral perirenal space.
      Pathologic evaluation after radical nephrectomy reported the perirenal mass to
      consist only of myelolipomatous change, however, further review identified
      liposarcoma.

PMID- 8284869
TI  - Stage T1A carcinoma of prostate.
AB  - When presented with a post-TURP patient with pathologically confirmed Stage T1a
      disease, several points should be considered (Fig. 1). Is the patient's
      anticipated longevity and quality-of-life likely to be affected by the confirmed
      diagnosis? From current knowledge, men over the age of seventy or with co-morbid
      risk factors probably will not be adversely affected, and no treatment is
      required apart from expectant follow-up with semiannual DRE and serum PSA
      determinations. The group at risk seems to be the young patient with a Stage T1a
      tumor who is likely to survive more than ten years after the diagnosis. Data
      showing progression rates without treatment as high as 16-25 percent at eight to
      ten years seem to indicate the need for additional therapy. If the patient
      belongs to this category and is ready to pursue more aggressive treatment,
      reestablishing the diagnosis might be suggested, as well as an evaluation of the
      pre- and post-TUR PSA levels. This can be done by TRUS-guided biopsies of the
      prostate (or repeat TURP, which we regard as less preferable). If residual tumor
      is not found, we would counsel a "wait and see" approach. If subsequent tissue
      sampling identifies other than well-differentiated cancer or indicates the
      likelihood of more extensive cancer than the T1a staging, treatment would be
      suggested. If the restaging reveals some residual well-differentiated disease
      that would not alter the initial staging of T1a, the patient should be offered
      the alternatives of close monitoring, radical prostatectomy, or radiation
      therapy. Until prognostic factors such as DNA ploidy and nuclear roundness are
      better studied, we are unable to counsel the patient on the biologic
      significance/aggressiveness of his Stage T1a disease.

PMID- 8284870
TI  - Percutaneous approach to indeterminate caliceal filling defects.
AB  - Although the radiologic characteristics and endoscopic appearance of aberrant
      renal papillae have been described, a tissue diagnosis is the only way to exclude
      a low-grade urothelial malignancy. We report on three caliceal filling defects
      managed percutaneously in which biopsy findings confirmed aberrant papillae.

PMID- 8284871
TI  - Duplication of inferior vena cava: its importance in retroperitoneal surgery.
AB  - Anomalies of the inferior vena cava arise infrequently. Knowledge of their
      presence can be established preoperatively with a variety of radiologic studies.
      This knowledge can prevent hemorrhagic complications from occurring during
      surgery. We present a case report of a patient with renal cell carcinoma and
      duplication of the inferior vena cava.

PMID- 8284872
TI  - Retroperitoneal tumor eleven years after initial treatment of testicular cancer.
AB  - Presented is a case report of retroperitoneal tumor eleven years after
      orchiectomy for testicular cancer. Complete remission was achieved with combined
      chemotherapy and retroperitoneal lymph node dissection. Histologic examination
      revealed that primary testicular tumor was pure choriocarcinoma and that the
      retroperitoneal tumor was likely embryonal cell carcinoma without foci of
      choriocarcinoma. It is difficult to determine whether the retroperitoneal tumor
      is a late recurrence of testicular cancer of a primary extragonadal germ cell
      tumor.

PMID- 8284873
TI  - Papillary mesothelioma of the albuginea testis.
AB  - An eleven-year-old boy is presented with symptom of a torsion of the testis.
      Scrotal exploration revealed a papillary mesothelioma of the tunica albuginea
      which is extremely rare in childhood. We report 1 case and review the literature.

PMID- 8284874
TI  - Bacillus Calmette-Guerin immunotherapy for refractory interstitial cystitis.
AB  - OBJECTIVE: To determine whether or not patients with refractory interstitial
      cystitis who had failed conservative therapy might benefit from intravesical
      bacillus Calmette-Guerin (BCG) immunotherapy. METHOD: Five patients with
      refractory interstitial cystitis who had failed conservative therapy underwent
      six weekly treatments with intravesical BCG. All 5 patients were evaluated before
      therapy and quarterly thereafter by water cystometry and symptom questionnaire.
      RESULTS: The average number of medications used daily per patient decreased from
      3.2 to 1.2 after therapy. Average volumes of both first desire to void and
      cystometric capacity doubled after BCG. Improvement in cystometric capacity,
      average daytime urinary frequency, nocturia, and global pain/discomfort were
      statistically significant (P = 0.0277, P = 0.0131, P = 0.0199, and P = 0.0317,
      respectively). Three patients experienced near total relief of their symptoms
      with six to twelve months' follow-up (average follow-up equals 33.6 weeks).
      CONCLUSIONS: Although the mechanism of action of BCG in interstitial cystitis is
      unknown, we recommend a double-blind placebo controlled trial to confirm these
      results and determine an optimal dosage and treatment schedule.

PMID- 8284875
TI  - Three-dimensional imaging and display of renal tumors using spiral CT: a
      potential aid to partial nephrectomy.
AB  - OBJECTIVE: A new technique for creating three-dimensional (3D) images of renal
      tumors using contrast-enhanced spiral computed tomography (CT) is described and
      preliminarily investigated. METHODS: 3D spiral CT was employed in 2 patients
      before radical nephrectomy and in 5 patients before partial nephrectomy.
      Preoperative and postoperative image analyses were conducted to evaluate the
      ability of the images to depict key anatomic relationships in planning partial
      nephrectomies. RESULTS: 3D spiral CT defined the tumor's location and
      relationship to the kidney surface better than the tumor's proximity to renal
      hilar vessels and collecting system. Negative surgical margins were obtained in
      all 4 patients with renal cell carcinoma, and post-operative serum creatinine
      remained less than 2 mg/dL in all 5 patients after partial nephrectomy.
      CONCLUSIONS: This early experience suggests that 3D spiral CT can help in the
      planning of partial nephrectomy and in attaining complete resection of renal cell
      carcinoma while conserving normal renal tissue.

PMID- 8284876
TI  - The natural history of early untreated prostate cancer.

PMID- 8284877
TI  - Simultaneous penile and urethral agenesis.

PMID- 8284878
TI  - Krukenberg tumors.

PMID- 8284879
TI  - Major renal trauma in children.

PMID- 8284880
TI  - Similarity of generic quinolone drug names.

PMID- 8284881
TI  - Endopyelotomy: patient selection, results, and complications.
AB  - The popularity of minimally invasive surgical techniques, such as endopyelotomy,
      has increased markedly among urologists in recent years. While it was initially
      thought that this procedure was best utilized in patients with secondary UPJ
      obstruction, recent evidence suggests that endopyelotomy should be considered in
      the majority of cases. The primary contraindication to endoscopic incision of the
      UPJ is a long stricture, although a large redundant renal pelvis and the presence
      of crossing lower pole vessels are considered by some to be relative
      contraindications as well. Although the majority of surgeons have used a
      percutaneous, antegrade approach to endopyelotomy, successful results also have
      been reported with a ureteroscopic, retrograde technique. With the development of
      modified ureterotomes and balloon-cutting devices, the retrograde approach
      eventually may become the preferred method since no skin incision or external
      drainage are needed. The role of endopyelotomy in children remains undefined.
      While successful results have been reported in infants, the relative morbidity
      and long-term success of open pyeloplasty in this age group are excellent, thus
      limiting the relative advantage of an endoscopic approach. However, there may be
      a role for endopyelotomy in older children and in those patients with secondary
      obstruction who have failed open surgery. From a technical standpoint, there are
      several minor variations in surgical technique and postoperative management that
      are important. The success rate of endopyelotomy using a cold knife or small
      electrocautery probe appears to be comparable, and the use of cautery may allow
      for precise control of minor bleeding thus decreasing the risk of complications.
      However, larger electrodes may induce greater tissue reaction leading to fibrosis
      and should be avoided. Postoperatively, most authors prefer a tapered double
      pigtail stent which allows for adequate internal drainage while avoiding
      excessive pressure within the distal ureter. While successful results have been
      reported with stenting intervals of only four days, it is generally recommended
      that the stent be left in place for a minimum of six weeks following endoscopic
      incision of the UPJ. Overall, endopyelotomy is associated with shortened
      hospitalization, more rapid return to normal activity levels, and decreased
      morbidity compared with open pyeloplasty. The success rates reported with
      endopyelotomy approach those achieved with open surgery, and it is likely that an
      endoscopic approach to UPJ obstruction will assume an increasingly greater role
      in the future.

PMID- 8284882
TI  - Clinical follow-up in 24 nonfamilial renal tumors cytogenetically characterized
      in tissue culture.
AB  - OBJECTIVE: This study investigates the relationship between clonal chromosomal
      abnormalities detected in nonfamilial renal cell carcinoma and the clinical
      outcome, specifically, whether or not patients whose tumors had karyotypic
      changes have a different prognosis than those whose tumors did not. METHOD: Fresh
      tumor tissue obtained from 32 cases was grown in tissue culture. Twenty four grew
      successfully and were harvested and multiple cells of each karyotyped. Clinical
      follow-up was obtained for at least five years or until the time of death.
      RESULTS: Fourteen of 24 cases demonstrated karyotypic abnormalities including
      loss of Y chromosome (64%), trisomy 7 (50%), trisomy 12 (14%), trisomy 9, 10, 14,
      15, 16, and 17, monosomy 9 and 20, and long-arm deletion of chromosome 16 (1 case
      each). Tumors were well-differentiated in 16 cases, moderately differentiated in
      5 cases, and poorly differentiated in 1 case; 13 cases were pathologic Stage I, 5
      Stage II, and 6 Stage III. Thirty-three percent of the patients demonstrated
      clinical progression. CONCLUSIONS: No significant difference in prognosis could
      be found between patients with and without karyotypic abnormalities. The only
      clinical or pathologic difference which could be established was sex
      distribution. Significantly greater numbers of males had karyotypic abnormalities
      than females, but this could be explained by the high number of Y chromosome
      deletions that were detected. The lack of correlation between karyotypic
      abnormalities and clinical outcome may reflect a confounding factor in genetic
      evolution such that clinically determining chromosomal changes present early in a
      tumor's growth in vivo may no longer be present when the tumor is diagnosed,
      treated, or after it is grown in culture. This may make demonstration of such
      clinically significant chromosomal changes very difficult.

PMID- 8284883
TI  - Effects of verapamil, prostaglandin F2 alpha, phenylephrine, and noradrenaline on
      upper urinary tract dynamics.
AB  - OBJECTIVES: The effects of verapamil (VRP), prostaglandin F2 alpha (PGF2 alpha),
      phenylephrine, and noradrenaline on upper urinary tract dynamics were studied in
      vivo, using a pig model involving 12 miniswine which were subjected to acute
      pharmacologic perfusion studies of the upper urinary tract. METHOD: Changes in
      renal pelvic pressure (Ppvs) and ureteral peristalsis frequency were recorded at
      2 mL/min perfusion rate premedication, and then during perfusion with different
      concentrations of each drug tested in three experiments. RESULTS: Ppvs showed no
      significant variations with VRP perfusion when compared with premedication
      readings, whereas ureteral peristalsis frequency was decreased significantly by
      10(-3) mol/L of VRP. PGF2 alpha perfusion caused no statistically significant
      changes in Ppvs when compared with premedication values, but increased ureteral
      peristalsis frequency from 3 to 6.5/min at a concentration of 2 x 10(-1) mg (200
      micrograms). Phenylephrine HCl and noradrenaline perfusion increased Ppvs from 8
      +/- 1.1 to 11.9 +/- 1.6 cm water at a concentration of 100 micrograms. They
      augmented the frequency of ureteral peristalsis from about 2.5 +/- 1.2 to 4.1 +/-
      1.3/min. No systemic effects were recorded since pulse, respiration, and left
      ureteral activity were unchanged during pharmacologic perfusion of the right
      side. CONCLUSION: Pharmacologic manipulation of ureteral activity can be achieved
      via direct perfusion with no significant modulation of Ppvs or systemic impact.
      VRP-induced smooth muscle relaxation of the upper urinary tract may be useful in
      percutaneous surgery for stones.

PMID- 8284884
TI  - Bladder distention therapy for symptomatic relief of frequency and urgency: a ten
      year review.
AB  - OBJECTIVE: A retrospective review was undertaken to determine the efficacy of
      bladder distention therapy for the treatment of frequency and urgency, and to
      determine the relative value of prolonged versus short duration distention
      therapy. METHOD: Prolonged bladder distention therapy was performed on 14
      patients and short duration distention on 8 patients over a ten-year period.
      Indications for the procedure included severe urgency, frequency, and
      incontinence from a variety of etiologies. RESULTS: Five of 14 patients (18
      distentions, 2 bladder ruptures) who had prolonged distention, and 3 of 8
      patients (9 distentions, 1 bladder rupture) who had short duration distention
      experienced symptomatic relief on follow-up (p > 0.7). Since there was no
      difference between the prolonged and short duration groups, the results were
      combined to yield 8 of 27 successful distentions (30%) in 8 of 22 patients (36%).
      All patients with detrusor hyperreflexia failed distention therapy. Complications
      included 3 cases of bladder rupture, 2 cases of urinary retention, and 1 case of
      urethral stricture. The rates of bladder rupture were identical in both groups
      (11%). CONCLUSIONS: The use of prolonged bladder distention therapy has no role
      in the treatment of detrusor hyperreflexia, and only limited success in the
      symptomatic relief of severe urgency, frequency, and incontinence of other
      etiologies. Equal efficacy of prolonged and short duration distention therapy
      would tend to favor the use of short duration distention to reduce possible
      anesthesia complications and cost.

PMID- 8284885
TI  - Raz bladder neck suspension in women younger than sixty-five years compared with
      elderly women: three years' experience.
AB  - OBJECTIVE: To verify the efficacy of Raz bladder neck suspension in producing
      cure of genuine stress incontinence (GSI) in women younger than sixty-five years
      compared with elderly women, and to find out whether or not elderly patients are
      more prone to failure with this technique. METHOD: We reviewed our results with
      this procedure in 67 women younger than sixty-five years (group I) compared with
      21 elderly women (group II). Seventeen patients in group I and 4 patients in
      group II had bladder neck suspension for grade I-II incontinence, and 50 patients
      in group I and 17 in group II had additional cystocele repair by the four-corner
      technique. Rectocele repair and vaginal hysterectomy were also performed when
      indicated. RESULTS: With a mean follow-up period of 18.2 months for group I and
      16.8 months for group II, 57 women (85.1%) in group I were completely cured of
      stress incontinence, 6 (8.9%) had marked improvement, and 4 (6.0%) had
      recurrence, while in group II, 19 (90.4%) were completely cured, 1 (4.8%) had
      marked improvement, and 1 (4.8%) had recurrence. Namely, in group I, 94 percent
      of the patients were either cured or improved, as compared with 95.2 percent in
      group II (P = 0.6; Fisher's exact test). Postoperative complications were few,
      and there was no permanent urinary retention. CONCLUSION: We conclude that, in a
      relatively short-term follow-up, Raz bladder neck suspension is equally
      successful in curing stress urinary incontinence in young and elderly females.

PMID- 8284886
TI  - Heterogeneity of prostate cancer in radical prostatectomy specimens.
AB  - OBJECTIVE: To understand the morphologic and spatial relationships of the various
      grades of prostate cancer, we investigated whether poorly differentiated cancer
      usually arises within the center of a large, well-differentiated tumor or more
      often forms the periphery or leading edge of the tumor. METHODS: In a series of
      one hundred and one completely sectioned whole-mount radical prostatectomy
      specimens removed from patients with clinical Stage T2 prostate cancer, we mapped
      the distribution of each of the five Gleason grades and assessed their frequency,
      proportion, and spatial distribution. RESULTS: The average number of different
      grades present in our patients was 2.7 (range 1-5). Over 50 percent of the
      prostates contained at least three different grades of cancer. The number of
      different Gleason grades present increased significantly with increasing tumor
      volume (p < 0.0001). Only 10 percent of the index cancers (largest tumor present)
      were composed of a single grade and these cancers were small (0.02-1.7 cm3).
      Among cancers with multiple grades, the most common finding (53%) was a high
      grade cancer present within the core of a larger, more well-differentiated tumor;
      however, the opposite pattern, low-grade cancer present within a larger poorly
      differentiated cancer, was also common (30%) and predominated in very large
      cancers (> 10 cm3). CONCLUSION: Small prostate cancers are often composed of a
      single grade, usually Gleason grade 2 or 3. But most palpable cancers contain
      multiple grades which are arranged in heterogeneous and unpredictable geographic
      interrelationships.

PMID- 8284887
TI  - Laser treatment of urethral condyloma: a five-year experience.
AB  - OBJECTIVE: Twenty cases of men treated with the neodymium:yttrium-aluminum-garnet
      (Nd:YAG) laser for meatal and/or urethral condyloma over five years were
      reviewed. METHOD: All patients underwent Nd:YAG laser treatment of visible
      lesions as outpatients under general anesthesia using the visual urethrotome
      sheath and 0 degree lens. Follow-up urethroscopy was performed at three-month
      intervals. Cure of the gross disease was defined as negative findings on two
      sequential follow-up urethroscopies. RESULTS: All patients with gross
      condylomatous disease were verified to have type 6/11 human papillomavirus.
      Ninety-five percent had meatal condylomata of which 42 percent had concomitant
      distal urethral lesions. Thirty percent were cured of gross disease after one
      treatment, while 40 percent needed two, three, four, or five separate treatments
      before gross cure was obtained. Thirty percent had insufficient follow-up. Only 2
      of the patients experiencing recurrence did so after negative finding on one
      follow-up urethroscopy. CONCLUSIONS: We believe attempts at cure of gross
      urethral condylomatous disease should be made because of its unsightliness and
      symptoms such as split stream and bleeding. Cure of gross disease with the Nd:YAG
      laser, as evidenced by our results, is possible. However, it may require several
      treatments. Follow-up urethroscopy is recommended in all patients because of the
      high incidence of recurrence and concomitant distal urethral involvement in those
      patients with meatal disease.

PMID- 8284888
TI  - High attrition rate with intracavernous injection of prostaglandin E1 for
      impotency.
AB  - OBJECTIVE: To determine if intracavernosal pharmacotherapy utilizing
      prostaglandin E1 (PGE1) injections is a well accepted and durable treatment
      modality for impotency. METHOD: We reviewed the charts of 110 consecutive men who
      underwent a thorough impotency evaluation and were considered acceptable
      candidates for intracavernosal pharmacotherapy with PGE1. RESULTS: Forty patients
      opted not to initiate treatment with PGE1 (16 due to loss of interest in sex),
      while 60 patients pursued home self-injection therapy; 10 patients were lost to
      follow-up. Thirty-six (60%) of those who initiated therapy discontinued the use
      of PGE1 with a mean follow-up of six months; 18 terminated PGE1 usage due to loss
      of interest in sexual activity and 3 due to return of spontaneous erections.
      However, many who lost interest in sexual activity in both groups directly
      attributed this to the required intracavernosal route of administration for PGE1.
      Thus, only 24 of the original 100 (24%) patients continued to use PGE1 as
      impotency therapy for an attrition rate of 76 percent. CONCLUSION: Our study
      indicates that intracavernosal pharmacotherapy using PGE1 injection therapy is
      not a satisfactory long-term therapeutic modality for many patients with erectile
      dysfunction. The diverse reasons for this high attrition rate are discussed.

PMID- 8284889
TI  - Urologic manifestations of Goldenhar syndrome.
AB  - OBJECTIVE: Goldenhar syndrome (oculoauriculovertebral dysplasia) is associated
      with anomalies in multiple organ systems. Renal abnormalities have also been
      reported with the complex, but the incidence of associated genitourinary
      malformations has not been defined. METHOD: We have reviewed our experience with
      28 children with Goldenhar syndrome evaluated during the past twelve years.
      Twenty children underwent imaging evaluation of the urinary tract and 14 (70% of
      those imaged) children had urinary tract anomalies. RESULTS: The majority of
      anomalies presented as an incidental finding on a screening ultrasound (8
      patients) or during cardiac catheterization (2 patients). Two children presented
      with urinary tract infection, 1 child presented with renal failure, and another
      was diagnosed antenatally. The genitourinary anomalies included the following:
      ectopic and/or fused kidneys (8 patients), renal agenesis (7), vesicoureteral
      reflux (5), ureteropelvic junction obstruction (2), ureteral duplication (2), and
      multicystic kidney (1 patient). Four children have undergone surgical
      intervention. CONCLUSION: Our experience in children with Goldenhar syndrome
      suggests that the incidence of genitourinary anomalies is higher than previously
      reported. A screening ultrasound in the neonatal period allows for early
      intervention in those children with significant urologic abnormalities.

PMID- 8284890
TI  - Current indications for cutaneous ureterostomy.
AB  - OBJECTIVE: To assess the current indications for cutaneous ureterostomy in
      children. METHOD: A total of 32 children underwent cutaneous ureterostomy at
      Texas Children's Hospital from 1975 to 1990. Medical records were reviewed to
      determine the urologic diagnosis, the indication for urinary diversion, the type
      of ureterostomy performed, and the outcome for each patient. RESULTS: Twenty
      patients underwent loop cutaneous ureterostomy (LCU) or pyelostomy and 12
      patients underwent end cutaneous ureterostomy (ECU). The main indication for LCU
      was obstructive uropathy unresponsive to lower urinary tract drainage, and the
      most common cause was posterior urethral valves. Other indications for LCU
      included obstruction requiring delayed surgical correction, high-grade reflux
      into a solitary kidney, and obstruction with infection. The children who required
      ECU were an older, more diverse group than those who underwent LCU. The main
      indication for ECU was poor bladder function secondary to a variety of congenital
      anomalies, including prune-belly syndrome, posterior urethral valves, bladder
      exstrophy, and urogenital sinus defect. CONCLUSION: LCU is easy to perform and is
      an excellent method for achieving temporary upper urinary tract drainage. ECU is
      suited for long-term or permanent urinary diversion in children with at least one
      dilated ureter, and can provide a socially acceptable stoma when delayed
      reconstruction is necessary. Many children who were "permanently" diverted by ECU
      may be undiverted using newer reconstructive techniques.

PMID- 8284891
TI  - Congenital urethrocutaneous fistulas.
AB  - We report on 2 cases of congenital urethrocutaneous fistulas in otherwise normal
      children. There were no associated congenital anomalies. Satisfactory surgical
      results were obtained. Potential causes are discussed.

PMID- 8284892
TI  - Coronary arterial anatomy of the one-humped camel (Camelus dromedarius).
AB  - The detailed coronary arterial anatomy of seven camels was studied and compared
      with that of horses and cattle. In camels, there is a bilateral coronary supply,
      the right coronary artery being the larger. The left coronary artery follows the
      same pattern as that in horses. The ramus collateralis proximalis in camels
      separates off some distance away from the origin of the ramus interventricularis
      paraconalis, as in horses, whereas it separates of very quickly in cattle. The
      ramus collateralis distalis has two branches in camels, whereas the left distal
      ventriculi ramus does not branch. The ramus angularis is also absent but the left
      distal atrii ramus is present.

PMID- 8284893
TI  - Type, diameter and distribution of fibres in some respiratory and abdominal
      muscles of the goat.
AB  - This study was designed to determine the histochemical properties, size and
      composition of fibres in the diaphragm, intercostal and abdominal muscles of
      goats to clarify whether reported similarities in respiratory muscle physiology
      between goats and humans have a structural basis. Serial sections (10 microns) of
      muscular tissue from adult female goats were stained for myosin adenosine
      triphosphatase and reduced nicotinamide adenine dinucleotide dehydrogenase
      tetrazolium reductase activities; the fibres were classified into type I, IIA and
      IIB; and their mean diameter and composition were determined. Abdominal and
      intercostal muscles contained types I, IIA and IIB fibres in the ratio 1:1:1, and
      the mean diameter of the fibres ranged from 49.2 to 62.2 microns. In contrast,
      the diaphragm contained 58.9% type I and 41.1% type II fibres, and the latter
      could not be differentiated into types IIA and IIB. Diaphragmatic fibres were
      also smaller (36.9-40.9 microns). These findings contrast with those in humans,
      where the diaphragm, intercostal and abdominal muscles contain > 50% type I
      fibres and have fibres of identical diameter. The differences in fibre
      characteristics between the diaphragm, intercostal and abdominal muscles of goats
      and the differences between goats and humans need to be taken into consideration
      in interpreting the results from studies in respiratory muscle physiology.

PMID- 8284894
TI  - The association between antibody titres against Campylobacter fetus and milk
      production efficiency in dairy cattle.
AB  - The association between serological evidence of exposure to Campylobacter fetus
      and milk production performance was studied in 178 lactating cows from three
      California Dairy Herd Improvement Association herds using a cross-sectional study
      design in December 1986. ELISAs were used to determine the antibody titres
      against Campylobacter fetus, Haemophilus somnus and Leptospira hardjo, which were
      classified as either negative or positive. The status of a cow as negative or
      positive against C. fetus and H. somnus represents the serological evidence of
      natural exposure to the corresponding bacteria. However, the status against L.
      hardjo was assumed to be the level of vaccinal titre against this organism since
      all the cows studied had been vaccinated against this agent. The data on
      demographic and productivity variables relating to the current lactation of the
      cows were obtained from Dairy Herd Improvement Association individual cow records
      for December 1986. Four measures of milk production efficiency for the current
      lactation were used. The status against L. hardjo and other covariates suggested
      by previous studies were included in modelling the relationships of interest.
      Stepwise multiple linear regression was used to study the adjusted relationship
      of C. fetus with each measure of milk production efficiency. Multivariate
      analyses revealed that the adjusted relationships of C. fetus with the test-day's
      milk production, the extended 305-day milk production and the relative value of
      milk production were not significant (p > 0.1). However, after adjusting for
      possible covariates, C. fetus-positive cows had an average of 7.43% lower mature
      equivalent milk production than C. fetus-negative cows (p = 0.02).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8284895
TI  - A comparison of dot-blot assay with the synergistic haemolytic inhibition test in
      goats naturally infected with Corynebacterium pseudotuberculosis.

PMID- 8284896
TI  - The retrospective use of a peroxidase technique for confirmation of suspected
      canine distemper in Kenya.

PMID- 8284897
TI  - Preliminary findings from an experimental study of caprine besnoitiosis in Kenya.
AB  - Inoculation of cystozoites obtained from natural, chronic cases of caprine
      besnoitiosis produced clinical disease in goats but not in rabbits, mice, guinea
      pigs, hamsters, rats or cattle. Histological examination of tissue sections from
      the experimental animals showed Besnoitia cysts only in goats. This, together
      with field observations that cattle reared together with goats having
      besnoitiosis do not contract the disease, suggests that the Besnoitia species
      that infects goats in Kenya is host-specific and is not Besnoitia besnoiti. We
      suggest that the name Besnoitia caprae be adopted for the caprine pathogen.

PMID- 8284898
TI  - Mucosal uptake, mucosal transfer and retention of iron in veal calves.
AB  - A method for studying iron absorption in humans was adapted to veal calves. Three
      10-week-old calves with moderate (calves 1 and 2) or severe (calf 3) iron
      deficiency were given an abomasal injection of 59Fe and 51Cr and all their faeces
      were collected over 15 days in order to measure mucosal uptake, mucosal transfer
      and retention of iron. The mucosal uptake was 62.2, 53.4 and 71.8% in calves 1, 2
      and 3, respectively. The iron retention measured 14 days after administration of
      the test dose was 57.4, 52.3 and 56.4% in calves 1, 2 and 3, respectively.
      Maximal plasma activity was found in all three calves between 1 1/2 and 2 h after
      injection of the test dose. The plasma activity decreased rapidly, with a slight
      increase between the 5th and the 10th hour. After 21 h, less than 0.25% of the
      injected dose was still present in 1 litre of plasma. Not all the 51Cr was
      recovered in the faeces. No 59Fe was found in the urine but some 51Cr could be
      detected. The results of this study show that the method described is useful for
      measuring the different steps of iron absorption in iron-deficient veal calves.

PMID- 8284899
TI  - Disposition kinetics, urinary excretion and dosage regimen of kanamycin in
      buffalo calves following single intravenous administration.
AB  - The disposition kinetics and appropriate dosage regimen for kanamycin were
      investigated in buffalo calves following a single intravenous dose of 10 mg/kg
      body weight. The distribution and elimination half-lives were 0.12 +/- 0.01 h and
      1.94 +/- 0.11 h, respectively. The apparent volume of distribution and total body
      clearance were 0.2 +/- 0.01 L/kg and 92.9 +/- 3.69 ml/kg/h, respectively. About
      74% of the administered dose was excreted in urine in 24 h. A suitable dosage
      regimen for the intravenous administration of kanamycin was also calculated.

PMID- 8284900
TI  - Measurement of total respiratory impedance in dogs by the forced oscillation
      technique.
AB  - The resistance (Rrs) and reactance (Xrs) of the total respiratory system were
      determined at various frequencies in 14 healthy conscious beagle dogs. A
      pseudorandom noise pressure wave was produced at the nostrils of the animals by
      means of a loudspeaker adapted to the nose by a tightly fitting mask. A Fourier
      analysis of the pressure and flow signals yielded mean Rrs and Xrs, over 16 s, at
      frequencies from 2 to 26 Hz. The influence of the posture of the dog, the
      position of its head, the linearity of the respiratory system, the
      reproducibility of the method and the effects of upper and lower airway
      obstructions were studied. In sitting and standing healthy dogs with the head in
      the extended position, Rrs values increased progressively with frequency from 5.4
      +/- 0.4 (SEM) cmH2O L-1s at 6 Hz up to 8.8 +/- 0.7 cmH2O L-1s at 26 Hz, the mean
      resonant frequency being 6.1 +/- 0.5 Hz. No significant differences were observed
      between measurements performed with the head in the normal or the extended
      position. In a recumbent posture, all Rrs values were increased but Rrs was still
      dependent on the frequency in the same way (7.1 +/- 0.7 cmH2O L-1s at 6Hz up to
      10.0 +/- 0.5 cmH2O L-1s at 26 Hz). Tracheal compression also induced higher Rrs
      values without changes in the frequency dependence or in the resonant frequency.
      In anaesthetized dogs, airway obstruction was induced by inhalation of histamine
      (4 mg/ml for 5 min; the Rrs values tended to decrease with increasing frequency,
      and the resonant frequency was markedly increased.

PMID- 8284901
TI  - [Carcinoma of the lung in patients with pneumoconiosis].
AB  - From 614 patients with notified pneumoconiosis who died in 1964-1992 on necropsy
      carcinoma of the lungs was found in 87, i.e. 14.1% (in 48 it was the cause of
      death). The incidence in individual years did not differ significantly; on
      evaluation in relation to the diagnosis of pneumoconiosis an insignificantly more
      frequent incidence was found in complicated pneumoconiosis of miners. On
      evaluation by work places miners in black coal mines and workers in quarries were
      affected more frequently, the difference being at the borderline of statistical
      significance. As to the histological aspect, most frequently squamous cell
      carcinoma was involved, the site was most frequently in both upper lobes. The
      carcinoma was seven times associated with silicotic lesions, with
      anthracofibrotic lesions six times (a total of 14.9%). In lifetime carcinoma was
      detected in 55 of the patients who died, i.e. in 63.2%. As to aetiopathogenetic
      influences, the relationship with smoking is significant. The aetiopathogenesis
      of carcinoma of the lungs in patients with pneumoconiosis is most probably not
      uniform-the influence of smoking is beyond doubt, the carcinogenic effect of
      silica should be considered in patients with carcinoma in the scar. With regard
      to the repeatedly proved more frequent incidence of carcinoma of the lungs in
      patients with pneumoconiosis, frequent check-ups of patients with pneumoconiosis
      focused on possible detection of lung cancer are essential.

PMID- 8284902
TI  - [Recurrent exudative pericarditis--non-traditional therapy with colchicine].
AB  - Relapses are one of the most serious complications of exudative pericarditis.
      Optimal treatment which prevents exacerbation of the disease does not exist so
      far. Non-steroid antiphlogistic drugs are usually drugs of choice. Corticoids are
      used in more severe conditions or during frequent relapses. Development of a
      relapse, despite corticoid treatment, calls for more intense and prolonged
      corticoid treatment even when this treatment produces undesirable side-effects.
      Surgical methods do not always produce a lasting favourable effect, as the
      authors observed repeatedly in two patients from the group of patients referred
      to. The initial therapeutic findings after colchicine treatment in relapsing
      pericarditis are optimistic but it will be necessary to find in larger groups of
      patients the optimal method of implementation of this treatment.

PMID- 8284903
TI  - [Reactive arthritis in infectious diarrhea].
AB  - The authors made a ten-year analysis of the incidence of these complications.
      They describe a total of 16 cases of arthralgia at the onset of diarrhoea and
      nine cases of reactive arthritis. The paper deals with some clinical and
      laboratory aspects of the disease.

PMID- 8284904
TI  - [Extra-articular manifestations of rheumatoid arthritis].
AB  - The author gives an account of the incidence of extraarticular organ
      manifestations of rheumatoid arthritis. These manifestations cause deterioration
      of the prognosis of the disease and are evidence of the systemic character of
      rheumatoid arthritis, which cannot be conceived as an articular disease.

PMID- 8284905
TI  - [Present views on the osteoarthrosis syndrome].

PMID- 8284906
TI  - [Is diagnosis and therapy of gout a simple matter?].
AB  - In the first part of the paper the author deals with the problem of the diagnosis
      of acute gouty arthritis. The apparently easy diagnosis is made three times more
      frequently than corresponds to the actual position. Since 1977 Wallace's criteria
      are used. The focal point of the diagnosis is evidence of sodium urate crystals
      in the synovial fluid. Various methods of assessment are discussed. In the second
      part the author deals with treatment of acute gouty attacks. He mentions the
      advantages and disadvantages of treatment with colchicine, steroid and non
      steroid antirheumatic drugs. In the conclusion he analyzes treatment with
      allopurinol and uricosurics.

PMID- 8284907
TI  - [The importance of the HLA complex antigens in systemic rheumatoid diseases].
AB  - The submitted paper reviews contemporary knowledge on the clinical impact of
      assessment of HLA-complex antigens in systemic rheumatic diseases. The authors
      explain the term "relative risk" and its practical importance. As to antigens of
      the HLA-complex class I, attention was paid in particular to the importance of
      HLA B 27 in ankylosing spondylitis, other spondylarthropathies and reactive
      arthritis; in this part the review is supplemented by results of the authors' own
      research. As to antigens of the HLA-complex class II, attention was paid to the
      sub-area DR in rheumatoid arthritis and other diffuse affections of connective
      tissue. The advance in knowledge of the clinical impact of investigations of
      selected HLA-complex antigens in systemic rheumatic diseases is that in many
      instances it reveals an association not only at the level of the nosological unit
      but frequently also sub-unit with prognostically important clinical and
      biochemical manifestations, a typical autoantibody profile and sometimes also
      with the risk of a greater organ toxicity of drugs.

PMID- 8284908
TI  - [The primary importance of the kidneys in the development of essential
      hypertension].
AB  - The participation of the kidneys in the development of renovascular and
      renoprivic hypertension has been known for a long time. The kidneys are, however,
      important also in the development of essential hypertension: these views are
      based on transplantation studies on various types of hypertensive and
      normotensive rats and their hybrids and transplantation studies in patients. In
      the genesis of hypertension participates the dual regulation of blood pressure by
      the kidneys: a) the renin-angiotensin-aldosterone system in the renal cortex
      which is manifested by two mechanisms (high- and low-renin hypertension resp.)
      with a number of functional and metabolic effects of angiotensins and
      aldosterone, b) the medullipine system with the production of medullipine I by
      interstitial cells in the renal medulla and its transformation into effective
      medullipine in the liver. The latter prevents the vasoconstrictor effect of
      pressor factors. Some other vasopressor and vasodilatating factors participate in
      the regulation of blood pressure by acting as mediators. These findings have not
      only a theoretical but also an immediate impact on evaluation of the prognosis
      and selection of treatment of essential hypertension.

PMID- 8284909
TI  - [Resistance to diuretic therapy].
AB  - Sequential nephron blockade--the combination of several diuretic agents which
      inhibit sodium reabsorption at different nephron sites simultaneously--is an
      effective, but potentially dangerous means of treating resistant edema. Several
      drug combinations have been used successfully, especially they have included a
      loop diuretic (furosemide in most cases) and the distal tubule-acting diuretics
      (hydrochlorothiazide).

PMID- 8284910
TI  - [Alport's syndrome].
AB  - After a historical introduction the authors analyze contemporary views on the
      aetiology, pathogenesis and genetics, they characterize the clinical picture and
      histopathological findings in Alport's syndrome. They emphasize that Alport's
      syndrome is more frequent than generally reported and that it deserves therefore
      appropriate attention in the differential diagnosis of renal diseases. They draw
      attention to the results of most recent genetic research which makes it possible
      to detect gene carriers of Alport's syndrome as well as early prenatal and
      postnatal diagnosis of this most frequently progressing hereditary nephritis.

PMID- 8284911
TI  - [Hypercoagulation states].
AB  - Hypercoagulability is a condition where as a result of certain pathological
      changes in the blood inadequate cumulation of thrombocytes or fibrin occurs which
      finally can lead to arterial or venous thrombosis, depending on vascular wall
      damage. In the submitted review the authors analyze the most important inborn and
      acquired causes of hypercoagulation states. As to inborn causes, deficiens of
      natural anticoagulation proteins (antithrombin III, protein C, protein S) are
      most important as well as dysfibrinogenaemia, impaired fibrinolysis associated
      with deficiency of natural activators of fibrinolysis or increased activity of
      their inhibitors and homocystinuria. The most frequent acquired causes of
      hypercoagulation states are the presence of anticardiolipin antibodies ("lupus
      anticoagulans"), pregnancy, the use of oral contraceptives, malignity, nephrotic
      syndrome, postoperative conditions, diabetes mellitus and some other diseases.

PMID- 8284912
TI  - [Hypocalcemic states].
AB  - The authors review contemporary knowledge of acute and chronic hypocalcaemia.
      They mention in more detail the most typical symptom of acute hypocalcaemia,
      tetany, and emphasize some chronic symptoms of chronic hypocalcaemia. Diagnostic
      difficulties may arise in particular in epileptic states, hypocalcaemic organic
      psychosyndrome and cataract. Diagnosis of their hypocalcaemic cause is important
      from the therapeutic and preventive aspect. The authors mention also states which
      may cause hypocalcaemia and finally they give an account of therapeutic
      possibilities in acute and chronic hypocalcaemia. Data from the literature are
      supplemented by the authors' data on the prevalence, pathogenesis and treatment
      of hypocalcaemia.

PMID- 8284913
TI  - [A comprehensive plan for management of a hematologic laboratory].

PMID- 8284914
TI  - [A method of competitive dot hydridization for genotyping influenza A viruses].
AB  - A new method for genetic typing of influenza viruses using molecular
      hybridization of DNA-RNA was developed which consisted in addition to the
      hybridization solution, apart from the radioactively labeled probe, of RNA of a
      virus with known gene homologous to the plasmid DNA used as the probe but
      belonging to a different serosubtype of influenza A virus, other than cloned
      kDNA, (within the range of H1N1, H2N2, and H3N2). This competitive RNA (RNAc) is
      added in considerable excess with regard to both molecular probe and to RNA
      immobilized on the filter. Therefore hybrids of molecular probe DNA with RNAc are
      rapidly formed from which RNAc may be replaced only by those bRNA immobilized on
      the filter whose homology to the probe is higher than that of RNAc.

PMID- 8284915
TI  - [The use of saliva for study in the immunoenzyme analysis of postvaccinal and
      postinfectious immunity to influenza].
AB  - Paired specimens of blood sera, upper respiratory tract secretions, and saliva
      from healthy, influenza-infected, and live influenza trivaccine-immunized humans
      were tested in parallel by HI tests and enzyme immunoassay (EIA). The resulting
      comparative data suggest that determination by EIA of specific secretory IgA in
      the saliva may be recommended as an independent test for large-scale influenza
      diagnosis, evaluation of the immune status of people, and trials of influenza
      vaccines. By immunologic parameters, this method is not inferior to the standard
      ones. At the same time its advantages include simplicity and readily available
      large volumes of saliva even from children as well as no necessity to bleed
      subjects to be examined.

PMID- 8284916
TI  - [Antibody functional activity in immunization with influenza vaccines].
AB  - The functional activity of serum antibody had been shown previously to reflect
      the state of resistance to influenza more accurately than antibody concentration.
      The functional activity of antibodies in the vaccination process was studied. The
      immune response to influenza antigens was found to be accompanied by an increase
      in the functional activity of antibodies, the intensity of this increase was the
      highest in natural influenza infection, moderate after administration of live
      vaccines and the least after immunization with inactivated preparations. The
      vaccine strains may differ significantly in their capacity to stimulate antibody
      with high functional activity. The quantitative parameters of the functional
      activity of antibody are directly related to the antigen dose and frequency of
      antigenic stimulation.

PMID- 8284917
TI  - [The factors and cofactors affecting the heterosexual transmission of human
      immunodeficiency virus (HIV) infection].
AB  - HIV-infected women and men as well as their sexual partners were examined with
      the purpose of detecting the factors and cofactors facilitating the risk of HIV
      transmission in heterosexual contacts. Among HIV-infected women were predominant
      those who led promiscuous sex life, practicing sex life during menstruation,
      those with traumatic sex, with cervical erosion in the anamnesis, and women whose
      sexual partners showed signs of marked immunodeficiency. Cervical erosion in
      women with heterosexual contacts is the leading factor increasing the risk of
      infection transmission from women to man and vice versa.

PMID- 8284918
TI  - [An outbreak of poliomyelitis in Tajikistan in 1991 caused by the poliomyelitis
      virus type 1 in concomitant echovirus 19 infection].
AB  - In 1991 in Tajikistan 36 cases of acute poliomyelitis were recorded (spinal form
      27, bulbospinal 3, pontospinal 6 cases) in children ranging in ages from 6 months
      to 6 years. The outcome of the disease was fatal in 4 cases and with crude
      residual effects in 32 children. Out of 23 children examined, poliomyelitis virus
      type I was isolated from 13, antibodies to poliovirus type I in titres 1:16 to
      1:1024 were detected in 21 children, ECHO 19 virus was isolated from 5 children
      and antibodies to this virus in titres 1:16 to 1:8192 were demonstrated in 13
      children. The fresh isolates of poliomyelitis virus type I had rct+, DS+ and N+
      markers. The strains of ECHO 19 virus were highly pathogenic for monkeys causing
      deaths of the animals within 3-4 days. It is assumed that the main causative
      agent of the Tajikistan outbreak of poliomyelitis was a virulent "wild" variant
      of poliovirus type I. The preceding or concomitant infection with ECHO 19 virus
      (considering the data from the literature and the demonstrated high virulence of
      this agent for monkeys) could exert an aggravating effect on the course of
      poliomyelitis or, in some cases, be an independent cause of the disease and,
      possibly, death of the children.

PMID- 8284919
TI  - [The diagnosis of herpesvirus infection in patients with organ allografts].
AB  - The diagnostic value of three methods for detection of herpes virus infection
      caused by herpes simplex virus and cytomegaloviruses was investigated in patients
      with allotransplanted organs. The method of molecular hybridization was
      demonstrated to be more sensitive in diagnosing herpes virus infection than
      virological and cytological methods. Herpes virus infection can be effectively
      diagnosed by a complex of methods including the detection of cytomegalic cells in
      the urine and saliva.

PMID- 8284920
TI  - [A comparative evaluation of the immunogenicity and reactogenicity of recombinant
      vaccines against hepatitis B].
AB  - Controlled epidemiological studies were carried out to evaluate two recombinant
      vaccines against hepatitis B of Cuban and Belgian production by the parameters of
      reactogenicity, safety and antigenic activity. Two groups of adult subjects (n =
      73 each) and two groups of children (n = 30 each) were selected among those free
      from hepatitis B markers carrier state. The adults were given both preparations
      in a dose of 20 micrograms at intervals of 0-1-4 months, and the children
      received 10 micrograms at 0-1-2 months. The comparative studies showed both
      vaccines to be poorly reactogenic, safe and inducing anti-Hns in 80-100% of
      triply vaccinated subjects in titres within 100-500 IU. No statistically
      significant differences in the examined parameters were found in the two
      preparations tested.

PMID- 8284921
TI  - [An experimental model of the vertical transmission of the Coxsackie-group
      enteroviruses and its use in developing methods to prevent congenital
      coxsackievirus infection].
AB  - An experimental model of vertical transmission of Coxsackie group enteroviruses
      was developed in BALB/c mice the first generation of which was infected with
      Coxsackie A18 virus in the neonatal period. Persistence of the virus was
      demonstrated in all females of the first generation tested and in 90.9% to 100%
      of the animals of the next two generations. Cytochemical analysis of the enzyme
      status of lymphocytes revealed reliable relationship between the depression of
      energetic metabolism enzymes and the activity of virus amplification in the
      animals under study. The correction of aerobic respiration in pregnant females by
      administration of a complex of energy metabolism substrates and cofactors was
      accompanied by a significant reduction of the virus infection activity in the
      females and their offsprings as well as by prevention of transplacental infection
      in some litters. The experimental model of vertical transmission of enteroviruses
      is proposed for use in the development of methods for prevention of congenital
      Coxsackie virus infection. The authors express their deep gratitude to the
      sponsor of the publication--NOVRUZ Co., Turkmenistan.

PMID- 8284922
TI  - [The immunogenic properties of a recombinant vaccinia virus with an incorporated
      DNA copy of the 26S RNA of the Venezuelan equine encephalomyelitis virus].
AB  - A recombinant strain of vaccinia virus (VR26) containing a DNA-copy of the
      subgenomic 26S RNA of Venezuelan equine encephalomyelitis virus (VEE) inserted
      into the coding region of thymidine kinase (TK) gene was produced. This
      subgenomic RNA contained the genes for all structural proteins of the VEE virus,
      the strain Trinidad donkey (TRD). VR26 effectively expressed VEE virus
      glycoproteins on the membranes of the infected cells. Blood sera of VR26
      immunized animals were found to contain VEE virus-specific antibodies. VR26
      immunized mice and rabbits showed a high level of resistance to subcutaneous
      inoculation with the pathogenic TRD strain of VEE virus. VR26 also provided a
      high level of protection in animals against aerogenic infection. The absence of
      virus-neutralizing antibodies in most VR26-immunized animals resistant to
      inoculation with high doses of VEE suggests the dominant role of the cell
      component in the immune response. The immune response induced by the recombinant
      VR26 strain was stable as demonstrated by the resistance of the animals to a
      challenge with VEE virus 7 months after immunization. The experimental results
      suggest that this recombinant strain may be considered as a candidate for vaccine
      preparation.

PMID- 8284924
TI  - [New properties of trental as an inhibitor of viral activity with a wide range of
      activity].
AB  - Experimental investigations on the spectrum and degree of the expression of
      trental antiviral activity were carried out. The investigations were done in cell
      cultures and laboratory animals using laboratory strains (including drug
      resistant ones) of 13 viruses, causative agents of human and animal infections.
      The drug demonstrated its activity against 8 viruses of 7 families. It was highly
      active against 5 viruses: herpes simplex virus (including its acyclovir-resistant
      strain), vaccinia virus (including its methisazone-resistant strain), rotavirus
      and tick-borne encephalitis virus. As regards other viruses, its activity was
      less pronounced (hepatitis JA virus) or low (vesicular stomatitis virus, West
      Nile virus). It was concluded that, being a cardiovascular drug, trental was an
      effective broad spectrum virus inhibitor.

PMID- 8284923
TI  - [The immunity indices of BALB/c mice immunized with an inactivated antigen of the
      Machupo virus].
AB  - The paper presents the data characterizing parameters of specific and nonspecific
      immunity in BALB/c mice immunized with gamma-ray-inactivated Machupo virus
      antigen or its formalinized antigen. The gamma-ray inactivated preparation was
      shown to be more immunogenic for BALB/c mice. A certain relationship between the
      time course of activity of nonspecific immunity factors in the immunized animals
      and the protective activity of the preparation under study was also noted. The
      decisive role of the T-cell part of the immune system was demonstrated in the
      resistance of this model animal to Machupo virus infection.

PMID- 8284925
TI  - [The evaluation of the immunogenic activity of an experimental lot of a vaccine
      against rotavirus infection in cattle on an animal-breeding farm complex].
AB  - The immunogenic potency of an experimental vaccine against rotavirus infection of
      cattle was studied under production conditions. Cows with calves were vaccinated
      in the second period of pregnancy once, twice and three times. The study showed
      the schedule of immunization of pregnant cows including three vaccinations at 50
      40, 30-20, and 15-10 days before delivery to be technological, providing a high
      protective effect in newborn calves.

PMID- 8284926
TI  - [The pathology of a Chinese oak silkworm cell culture infected with the mosquito
      iridovirus].

PMID- 8284927
TI  - Reciprocity of involvement activities in client-nurse interactions.

PMID- 8284928
TI  - Patients' satisfaction with nurses' caring during hospitalization.

PMID- 8284929
TI  - Causal influences of psychological adaptation in dying.

PMID- 8284930
TI  - Spiritual caring behaviors as reported by Christian nurses.

PMID- 8284931
TI  - Limits of using patient characteristics in predicting home health care
      coordination.

PMID- 8284932
TI  - Nursing director responses to the rural hospital environment.

PMID- 8284933
TI  - The health motivation assessment inventory.

PMID- 8284934
TI  - Vulnerability: an ethical consideration in research with older adults.

PMID- 8284935
TI  - A problem-solving approach to technical research issues.

PMID- 8284936
TI  - Increasing the relevance of education for health professionals. Report of a WHO
      Study Group on Problem-Solving Education for the Health Professions.

PMID- 8284937
TI  - Implementation of the global malaria control strategy. Report of a WHO Study
      Group on the Implementation of the Global Plan of Action for Malaria Control 1993
      2000.

PMID- 8284938
TI  - Glutathione.

PMID- 8284939
TI  - Significance of an unusually low Km for glutathione in glutathione transferases
      of the alpha, mu and pi classes.
AB  - 1. Interactions of glutathione transferases (GST) of the alpha, mu and pi classes
      with glutathione (GSH) and glutathione conjugates (GS-X) are in contrast with
      those of a GST of the theta class (GST5-5). 2. GST 5-5 has a Km for GSH of
      approx. 5 mM. Thus Km/ambient [GSH] is approx. 1, within the range of Km/ambient
      [s] of glycolytic enzymes. GSTs of the alpha, mu and pi classes yield much lower
      values of Km for GSH (approx. 0.1 mM) hence Km/ambient [s] is significantly lower
      than those of most (non-GST) enzymes (p < 0.025). 3. GSTs of the alpha, mu and pi
      classes are sensitive to inhibition by GS-X (i.e. product) and GS-X analogues.
      GST 5-5 is not. 4. Rate enhancements up to 10(10), similar to an average enzyme
      (10(8)-10(12)), are seen in catalysis by GST 5-5, but not in catalysis by GSTs of
      alpha, mu and pi classes (> 10(7)). 5. Comparisons of primary structure indicate
      that theta class GSTs may have a decreased binding of the glu-alpha-amino- and
      gly-COO(-)-groups of GSH compared with GSTs of the other classes. 6. It is
      concluded that GSTs of alpha, mu and pi classes have evolved towards increased
      product binding at the expense of catalytic efficiency. Thus GSH is uniquely
      utilized both as a nucleophile and a 'tag' which can be used to bind and
      sequester product particularly during GSH-depletion. This interpretation unifies
      the catalytic and binding properties of these GSTs and alters their perceived
      role in detoxication.

PMID- 8284940
TI  - Glutathione transferases of classes alpha, mu and pi show selective expression in
      different regions of rat kidney.
AB  - 1. Glutathione transferases (GST) are mainly cytosolic and occur in multiple
      forms, which can be arranged in three distinct, structural classes. The different
      enzyme forms show distinct substrate specificities with electrophilic and
      genotoxic substances. The expression of the alpha subunits 1, 2 and 8, the mu
      subunits 3, 4 and 6, and the pi subunit 7 of GST in different parts of the rat
      kidney was determined immunohistochemically. 2. GST immunoreactivity was present
      predominantly in the nephron, collecting duct and urothelium. 3. A conspicuous
      finding was that subunits 1, 2 and 8 were localized to the proximal tubules,
      while the mu subunit 3 was demonstrable in epithelial tubular cells from the
      distal tubules to the urothelium. The immunoreactivity of subunits 4 and 6 could
      be visualized in epithelial cells from the ascending thin limb to the collecting
      ducts. Subunit 7 was found in the thin limb of the loop of Henle, and in
      scattered cells in the distal tubules. 4. The urothelial cells covering the
      papilla and the renal calyces showed immunoreactivity to GST subunits 2-4 and 6
      8. 5. Thus, in the nephron the class alpha GSTs were selectively expressed in the
      proximal tubules and the class mu and class pi GST in the thin loop of Henle and
      distal tubules. The cells in the collecting ducts and the urothelium, which have
      a different ontogeny than the nephron, do not show any corresponding differential
      distribution of the GST classes. 6. Cells in a given location were in some cases
      found to be non-reactive with a given antiserum in an otherwise immunoreactive
      cell population, demonstrating a spatial variation in GST expression. The
      immunoreactivity to the different forms of GST was predominantly cytoplasmic but
      a nuclear localization could also be demonstrated. 7. The panel of antibodies to
      GST may tentatively be used as markers in localizing lesions in restricted parts
      of the nephrons and to elucidate dynamic alterations in the tubular system in
      response to physiological and toxic agents.

PMID- 8284941
TI  - Separation of multiple forms of glutathione S-transferase from the blue mussel,
      Mytilus edulis.
AB  - 1. Glutathione S-transferase isoenzymes from Mytilus edulis and M.
      galloprovincialis have been partially purified by glutathione-sepharose affinity
      chromatography followed by Mono Q anion exchange fast protein liquid
      chromatography (f.p.l.c.). 2. The tissue distribution of glutathione S
      transferase in M. edulis has been studied. Using 1-chloro-2,4-dinitrobenzene as
      substrate, highest specific activity is observed in the gill, the main feeding
      organ. Affinity-purified extracts of this organ give a characteristic f.p.l.c.
      profile. A similar profile is obtained with affinity-purified extracts of the
      digestive gland of M. galloprovincialis. 3. The subunit structure of the purified
      isoenzymes has been studied by SDS polyacrylamide gel electrophoresis and
      reversed-phase h.p.l.c. The subunits have similar molecular weights and h.p.l.c.
      retention times to rat glutathione S-transferases.

PMID- 8284942
TI  - S-nitrosyl glutathione-mediated hepatocyte cytotoxicity.
AB  - 1. The addition of n-butyl nitrite (BN) to isolated rat hepatocytes caused rapid
      S-nitrosyl glutathione (GSNO) formation, then a concomitant decrease in protein
      thiols, followed by a marked ATP depletion. Cytotoxic concentrations of BN also
      caused lipid peroxidation after a long lag period but before cytotoxicity ensued.
      2. Prior glutathione (GSH) depletion protected hepatocytes against the BN-induced
      decrease in protein thiols, ATP depletion, lipid peroxidation and cytotoxicity.
      Thus cytotoxic effects were thought to be mediated via GSNO formed by reaction of
      BN with GSH, a reaction catalysed by the cytosolic fraction. 3. Cytotoxicity and
      lipid peroxidation, but not depletion of GSH, protein thiols or ATP, could be
      averted by the subsequent addition of antioxidants or the iron chelator,
      desferoxamine. 4. Addition of the thiol reductant, dithiothreitol to BN-treated
      hepatocytes restored GSH and protein thiols and also prevented cytotoxicity.

PMID- 8284943
TI  - Glutathione-dependent bioactivation of xenobiotics.
AB  - Glutathione conjugation has been identified as an important detoxication
      reaction. However, in recent years several glutathione-dependent bioactivation
      reactions have been identified. Current knowledge on the mechanisms and the
      possible biological importance of these reactions are discussed. 1.
      Dichloromethane is metabolized by glutathione conjugation to formaldehyde via S
      (chloromethyl)glutathione. Both compounds are reactive intermediates and may be
      responsible for the dichloromethane-induced tumorigenesis in sensitive species.
      2. Vicinal dihaloalkanes are transformed by glutathione S-transferase-catalyzed
      reactions to mutagenic and nephrotoxic S-(2-haloethyl)glutathione S-conjugates.
      Electrophilic episulphonium ions are the ultimate reactive intermediates formed.
      3. Several polychlorinated alkenes are bioactivated in a complex, glutathione
      dependent pathway. The first step is hepatic glutathione S-conjugate formation
      followed by cleavage to the corresponding cysteine S-conjugates, and, after
      translocation to the kidney, metabolism by renal cysteine conjugate beta-lyase.
      Beta-Lyase-dependent metabolism of halovinyl cysteine S-conjugates yields
      electrophilic thioketenes, whose covalent binding to cellular macromolecules is
      responsible for the observed toxicity of the parent compounds. 4. Finally,
      hepatic glutathione conjugate formation with hydroquinones and aminophenols
      yields conjugates that are directed to gamma-glutamyltransferase-rich tissues,
      such as the kidney, where they undergo alkylation or redox cycling reactions, or
      both, that cause organ-selective damage.

PMID- 8284944
TI  - Perturbation of glutathione status and generation of oxidative stress in mouse
      skin following application of contact allergenic sesquiterpene lactones and
      isothiocyanates.
AB  - 1. The sensitizing or non-sensitizing status of selected sesquiterpene lactones
      and isothiocyanates was confirmed in mouse by open epicutaneous application. 2.
      Glutathione status of mouse skin was determined 12 h after lactone/isothiocyanate
      application; glutathione S-transferase activity also was determined 12 h after
      lactone application. 3. NAD(P)H utilization by rat liver microsomal preparations
      exposed to the sesquiterpene lactones and isothiocyanates was measured. 4. A
      correlation was observed between sensitizing status and the ability to perturb
      glutathione status, to induce glutathione S-transferase activity, and to
      stimulate NAD(P)H utilization. 5. It was concluded that sensitizing sesquiterpene
      lactones and isothiocyanates could induce oxidative stress in mouse skin,
      possibly as a result of their reductive metabolism.

PMID- 8284945
TI  - Role of tissue glutathione in prevention of surgical trauma.
AB  - 1. Surgical trauma has been associated with pre-anaesthesia fasting, anaesthetic
      toxicity, haemorrhage, hypovolaemic shock, and other pathological phenomena.
      Tissue glutathione (GSH), thiobarbituric acid-reacting substances (TBAR), and
      radical-trapping activity (RTA) have been determined at various time intervals
      after fasting, anaesthesia, and also after hepatic ischaemia and reperfusion as a
      model for haemorrhage and hypovolaemic shock. 2. Light ether anaesthesia of rats
      resulted in an immediate (5 min) and progressive decrease in liver and kidney
      total glutathione (GSH and GSSG), which was much greater in animals that had been
      fasted for 20 h. TBARs, a measure of lipid peroxidation, in rat liver and kidney
      increased as total GSH decreased. Fasting (20 h) alone decreased tissue GSH by
      50%, and increased TBAR 100%; fasting plus 30 min of ether anaesthesia decreased
      tissue glutathione by 80 to 85%, and increased TBAR by some 600%. 3. Liver
      ischaemia alone decreased total liver GSH by 20% in the fed rat, and 50% in the
      fasted rat. Ischaemia, followed by reperfusion, decreased liver total GSH by 70%
      in the fed rat, and 90% in the fasted rat. The ratio of GSH/GSSG decreased from
      16 in control animals to 7 in the fasted ischaemic rat, then to 1 in the fasted,
      ischaemic rat reperfused for 90 min. RTA of liver closely paralleled liver total
      GSH levels. TBAR was increased by ischaemia alone (50-100%), but more (400%) by
      90 min reperfusion. 4. A complex series of molecular mechanisms including: (1)
      GSH depletion; (2) induction of CYP2E1 activity; (3) generation of reactive
      oxygen species; (4) lipid peroxidation; (5) cytokine release; and (6) leucocyte
      activation, are advanced to account for the toxic phenomena of surgical trauma
      and multiple system organ failure.

PMID- 8284946
TI  - Ethacrynic acid and its glutathione conjugate as inhibitors of glutathione S
      transferases.
AB  - 1. The diuretic drug ethacrynic acid (EA) is a potent reversible inhibitor of rat
      and human glutathione S-transferases (GST), with I50-values (microM) of 4.6-6.0,
      0.3-1.9 and 3.3-4.8 for alpha, mu and pi-class, respectively. 2. The reversible
      inhibition by the glutathione conjugate of EA is even stronger for alpha and mu
      class, with I50-values (microM) of 0.8-2.8 and < 0.1-1.2, respectively, while the
      I50 for the pi-class is 11. 3. Inhibition of rat and human pi-class GST also
      occurs by covalent binding of ethacrynic acid. 14C-ethacrynic acid, 0.8 nmol EA
      per nmol pi-class GST could be incorporated, resulting in 65-93% inhibition of
      the catalytic activity. 4. Owing to the chemical nature of the covalent binding
      (Michael addition), this reaction should be reversible. Indeed, full restoration
      of the catalytic activity of GST P1-1 inactivated by covalently-bound EA was
      reached in about 125 h by incubation with an excess of glutathione. 5. EA has
      been used to inhibit GST in biological systems. The reversible covalent binding
      may very well play a role in the observed inhibition of GST by EA in vivo.

PMID- 8284947
TI  - Hexobarbital metabolism: a new metabolic pathway to produce 1,5
      dimethylbarbituric acid and cyclohexenone-glutathione adduct via 3'
      oxohexobarbital.
AB  - 1. In the presence of glutathione under physiological conditions, 3'
      oxohexobarbital was non-enzymically converted to 1,5-dimethylbarbituric acid and
      a cyclohexenone-glutathione adduct. 2. The two reaction products were
      characterized by mass spectrometry, 1H- and 13C-n.m.r. spectrometry, and UV
      spectral analyses. 3. 1,5-Dimethylbarbituric acid was excreted in urine of rat
      given hexobarbital, 3'-oxohexobarbital, or 1',2'-epoxyhexobarbital, and accounted
      for 13.4, 14.5 and 4.7% of dose, respectively. 4. The cyclohexenone-glutathione
      adduct, a novel metabolite of hexobarbital, was excreted in the bile of rat given
      hexobarbital. 5. The route of 1,5-dimethylbarbituric acid formation via 3'
      oxohexobarbital in the metabolism of hexobarbital was discussed in comparison
      with the epoxide-diol pathway.

PMID- 8284948
TI  - Identification and quantitative determination of glutathione-related urinary
      metabolites of fotemustine, a new anti-cancer agent.
AB  - 1. Potential sulphur-containing metabolites of the anticancer agent, fotemustine,
      were synthesized, namely thiodiacetic acid (TDA), S-2-hydroxyethyl N-acetyl-L
      cysteine (2-HE-NAC), N-acetyl-L-cysteine (NAC), S-methyl N-acetyl-L-cysteine (M
      NAC), S-carboxymethyl-L-cysteine (CM-Cys), S-carboxymethyl N-acetyl-L-cysteine
      (CM-NAC), their corresponding sulphoxides and sulphones. Their chemical
      structures and stabilities were confirmed and derivatization methods were
      developed for their analysis by sulphur-selective g.l.c. (g.l.c.-FPD) and g.l.c.
      mass spectrometry. 2. Four methods for isolation of potential metabolites of
      fotemustine were developed. Quantification of metabolites, derived in various
      ways was carried out by g.l.c.-atomic emission detection (AED) or g.l.c.-mass
      spectrometry. 3. Male Wistar rats (n = 4) were given a single i.p. dose of 40
      mg/kg fotemustine. Urine excretion of TDA (18.4 +/- 1.9% in 24 h) and TDA
      sulphoxide (12.0 +/- 1.6% in 24 h) was significant; 32.7 +/- 4.6% of the
      fotemustine dose was excreted as TDA, and TDA sulphoxide in 48 h. NAC was
      excreted in rat urine at 1% of the dose. No other potential glutathione-derived
      metabolites of fotemustine were excreted. 4. Male Wistar rats (n = 4) were also
      treated i.p. with fotemustine at 5, 20 and 40 mg/kg, to investigate dose
      dependency and the time course of excretion of TDA. Excretion of TDA in 48 h
      urine decreased from 32 +/- 2 to 17 +/- 2% dose (mean +/- SD) with increasing
      dose of fotemustine.

PMID- 8284949
TI  - Glutathione-mediated methylthio-turnover and sex differences in the metabolism of
      pentachlorothioanisole by rat.
AB  - 1. Sex differences observed in the metabolism of pentachlorothioanisole in rat
      were due to: (1) greater excretion in urine by females, and greater biliary
      excretion by males; (2) formation of pentachlorophenyl mercapturic acid pathway
      metabolites by females; and (3) redox-cycling between methylthio and
      methylsulphoxyl oxidation congeners in intermediary metabolites by females. 2.
      Three methylthio-turnover processes are proposed in the intermediary metabolism
      of pentachlorothioanisole.

PMID- 8284950
TI  - Investigations on the antibacterial effect of conifer needle oils on bacteria
      isolated from the feces of captive Capercaillies (Tetrao urogallus L., 1758).
AB  - In winter, free-living Capercaillies feed almost exclusively upon needles of
      various conifer species. An important part of the energy and protein requirements
      of captive Capercaillies, however, is supplied by food rich in starch and
      proteins. The fecal flora of captive Capercaillies is considerably different from
      the flora of free-living Capercaillies. Bacterial diseases are frequent in
      captivity. The aim of the present study is to determine whether the essential
      oils from conifer needles possess antibacterial properties against several
      bacteria, some of which are facultatively pathogenic for Capercaillies. Needles
      of Pinus sylvestris contain few tannins, which could be a reason for the
      Capercaillies' preference for these needles. The needles of Abies alba contain
      high amounts of tannins and essential oils, which could explain the refusal of
      Capercaillies to eat these needles. The antibacterial effect of commercially
      available essential oils on the bacteria is investigated with a filter paper disc
      method and in a liquid medium. The essential oils possess a bacteriostatic or a
      bactericidal effect against some of the tested bacteria. Feeding on natural
      forage plants may help prevent the colonization of the intestines by
      facultatively pathogenic bacteria. The authors discuss why Capercaillies,
      especially young birds that are to be released, should be fed with natural forage
      plants.

PMID- 8284951
TI  - Oxygen concentration and asexual development of Eimeria tenella in cell cultures.
AB  - Primary chicken kidney cells in Flexiperm cultures were either inoculated with
      Eimeria tenella sporozoites or incubated as noninoculated controls. Oxygen
      concentration was reduced (10 or 15 vol% O2, 5 vol% CO2) or increased (25 or 30
      vol% O2, 5 vol% CO2) in a triple gas incubator (Heraeus B 5061 EK/O2) and
      retained in a CO2-air incubator (20 vol% O2, 5 vol% CO2) 24 hours post
      inoculation (hpi). Mature second generation schizonts (mS2) were counted
      microscopically at 120 hpi and numbers were compared either as mS2 or mS2/cm2
      confluent cells. Asexual development of Eimeria tenella was neither stimulated
      nor inhibited by different oxygen concentrations, indicating that higher numbers
      of schizonts in cultures under reducing conditions reported earlier are probably
      a result of increased invasion rates of sporozoites.

PMID- 8284952
TI  - Detection of galactomannan and the 18 kDa antigen from Aspergillus fumigatus in
      serum and urine from cattle with systemic aspergillosis.
AB  - Serum and urine samples from cattle with experimental and spontaneous systemic
      mycotic infections were tested for the presence of galactomannan and the 18 kDa
      antigen from Aspergillus fumigatus by an inhibition ELISA and immunoblotting,
      respectively. High levels of galactomannan (approximately 80 ng/ml.) were
      detected in serum from two of three calves experimentally infected with A.
      fumigatus. In two out of three cows with spontaneous acquired aspergillosis a
      similar amount of galactomannan was detected. Galactomannan was not found in
      serum samples of 20 cows which aborted due to either experimental or spontaneous
      placental aspergillosis. Twenty-four of forty urine samples from normal cattle
      reacted positively in the ELISA, consequently, the assay was not applicable on
      bovine urine. The 18 kDa antigen from A. fumigatus was detected in the urine from
      one calf out of three calves experimentally infected with aspergillosis and in
      the urine from one cow with spontaneous aspergillosis. It is concluded that
      detection of galactomannan in serum and the 18 kDa antigen in urine may be used
      as an aid for the diagnosis of disseminated bovine aspergillosis with the
      exception of placental and probably gastrointestinal localization.

PMID- 8284954
TI  - Spinal dysmyelination in new-born brown Swiss x Braunvieh calves.
AB  - In four new-born Braunvieh calves suffering from connate recumbency and body
      tremor, a hitherto not described myelination disorder of the spinal cord was
      examined. Bilateral symmetric hypo- as well as demyelination in several spinal
      tracts were the most conspicuous findings, affecting the ascending gracile
      funiculus, the ascending dorsolateral spinocerebellar tract, and the mainly
      descending sulcomarginal tract. Deficient myelin production, loss of myelin,
      consecutive axonal degenerations, and prominent astrogliosis within these tracts
      were the histological hallmarks of the disease. This possibly inherited primary
      myelination disorder of the spinal cord differs markedly from known hereditary
      neurological diseases in Brown Swiss and Braunvieh cattle, respectively, i.e. the
      weaver-syndrome and the spinal muscular atrophy.

PMID- 8284953
TI  - Effect of age on serum concentrations of the third component of complement in
      dogs.
AB  - Single radial immunodiffusion was used to determine the concentration of the
      third component of complement (C3) in canine sera from 48 normal dogs in the
      following age groups: < 12 months, 12 to 24 months, and > 24 months. Mean serum
      C3 concentrations, expressed as the percentage of pooled reference sera from 20
      dogs, showed a significant (P < 0.017) correlation with age in dogs less than 12
      months old, while the character of this correlation was negative for dogs more
      than 24 months old (P < 0.056). Two-way analysis of variance, for age and sex,
      revealed significant differences between C3 values from this two groups that were
      not present when compared with dogs aged between 12 and 24 months old. Sex had no
      effect on serum C3 concentrations.

PMID- 8284955
TI  - [Aerogenous immunostimulation of weaner swine against experimentally induced
      respiratory infections with Pasteurella multocida].
AB  - The clearance of Pasteurella, Bordetella and Haemophilus from the lung of weaners
      was increased by aerogenous immunostimulations using a lysate mixture consisting
      of 12 strains of 8 bacterial species, as well as live and inactivated temperature
      sensitive mutants of Pasteurella multocida. The severity of experimental
      pneumonias caused by Pasteurella has also been decreased by this treatment. The
      effect of the lysate was shown to be unspecific and short, as antibody production
      against Pasteurella was not induced and no booster effect of subsequent
      aerogenous immunizations with Pasteurella antigens could be detected.

PMID- 8284956
TI  - Relation between serotype of streptococci of serological group B and growth rate
      at early logarithmic phase.
AB  - Determination of growth rate of streptococci of serological group B at early
      logarithmic phase by measuring optical density of the growth medium and by
      measuring the change of conductivity of the culture fluid appeared to be closely
      related to the serotype of the respective cultures. Most of the human and bovine
      group B streptococci with type patterns Ia/c, II, III and IV exhibited clearly
      visible growth of the culture medium after 4 h incubation and changed the
      conductivity of the culture fluid to a point defined as time to detection within
      4 h. No comparable growth could be observed with most of the cultures possessing
      type antigens R and X, either alone, or in combination with polysaccharide
      antigens. The importance of type specific capsule sialylation to the growth rate
      of the bacteria could be additionally shown with two group B streptococci of
      serotype III and their transposon mutagenized asialo capsular mutants. Both
      sialylated wild-type group B streptococci grew much quicker than their asialo
      capsular mutants. The results from additional experiments revealed that the
      growth velocity seemed to be significantly related to the chain length of the
      bacteria, to growth patterns of the group B streptococci in fluid media and soft
      agar and to the surface hydrophobicity of the bacteria. Determination of growth
      rate at early logarithmic phase could be used to predict various degrees of
      capsular sialylation of group B streptococci. This might help to understand the
      pathogenicity of individual group B streptococcal isolates in clinical cases.

PMID- 8284957
TI  - Endometritis in cattle experimentally induced by Chlamydia psittaci.
AB  - On the day of estrus, eight virgin heifers received intrauterine inoculations of
      yolk sac propagated Chlamydia psittaci strain BovEnd 11/88 isolated from the
      uterus of a slaughter cow. All heifers developed purulent vaginal discharge which
      persisted for 3 to 7 weeks. Chlamydiae or chlamydial antigen were detected in
      vaginal and uterine discharges of infected animals by culture or Capture ELISA,
      while other bacterial pathogens were not found. In sera of the chlamydia-infected
      heifers marked increases in antibody titres against the chlamydial genus-specific
      LPS-antigen were found by ELISA and complement fixation test. Six heifers were
      artificially inseminated in 5 successive cycles beginning at the first estrus
      following intrauterine inoculation. In two of the infected heifers spontaneous
      healing of endometritis occurred after 5 estrus cycles. Only these animals
      conceived after the 5th breeding, whereas in the remaining four animals a
      chlamydia-associated chronic endometritis was recognized as the cause of
      infertility in the 19th and 26th week p.i. at slaughter. Two control heifers
      which remained clinically normal after intrauterine exposure to sterile yolk sac
      suspensions conceived at the 1st and 2nd service, respectively.

PMID- 8284958
TI  - Isolation of Chlamydia psittaci from a chicken egg: evidence of egg transmission.

PMID- 8284959
TI  - [The infection risk for dogs raised helminth-free in conventional conditions in
      an urban area].
AB  - The present investigations were carried out to clarify whether or not and to what
      extent helminth-free raised dogs acquire patent and impatent helminth infections
      when exposed to an urban area contaminated with dog faeces. Groups of each 3
      bitches at an age of 3, 6 or 9 months were taken out to an urban area (with
      average dog density of 1.5 per ha) for 3 hours daily on 5 days per week for a
      period of 3 month. During the whole trial the bitches and puppies born during
      this period were maintained under conditions which excluded other infections than
      those acquired during exposure in the urban area. The examination of the animals
      had the following results: All 9 bitches remained coproscopically negative until
      the end of the trial. In these bitches neither intestinal stages nor somatic
      helminth larvae were found. Seven out of 45 puppies from these bitches shed
      Toxocara canis eggs with the faeces. Shedding of eggs began 21 to 28 days after
      birth. Eggs excretion in most cases was low (< 33 eggs per gram). In 12 puppies
      from 5 litters intestinal stages of T. canis were found with a maximum of 4
      specimens per animal. In 9 puppies only male or female T. canis were found.

PMID- 8284960
TI  - Enzootic intranasal tumour of goats in Italy.
AB  - An outbreak of enzootic intranasal tumour (EIT) in a goat herd in Central Italy
      is described. From October 1990 to September 1992 41 tumors were diagnosed in
      goats ranging in age from 6 months to 6 years and of both the Alpine and Saanen
      breeds. Clinically the affected goats showed nasal discharge, facial swelling,
      sneezing and snoring respiration and weight loss. Post-mortem examinations
      revealed uni- or bilateral tumours of the olfactory mucous membrane. The
      neoplasms were classified as low grade adenocarcinomas. Ultrastructurally,
      retrovirus-like particles were observed in 10/10 tumours examined.
      Epidemiological and ultrastructural findings strongly suggest a viral aetiology
      for intranasal enzootic adenocarcinoma in the goats examined.

PMID- 8284961
TI  - Investigations on the aerobic flora and Clostridium perfringens in fecal
      specimens from free-living and captive capercaillies (Tetrao urogallus L., 1758).
AB  - 173 fecal specimens from captive Capercaillies and 92 fecal specimens from free
      living Capercaillies were examined bacteriologically. With all specimens the
      bacteriological examination was limited to the aerobic bacteria which can be
      isolated by the usual methods and to Clostridium perfringens. The occurrence of
      fungi and parasites was examined as well. The present paper compares the results
      of these examinations. The identifiable fecal flora of free-living Capercaillies
      consists of few species with low colony numbers. In about half of the specimens
      Bacillus spp. are the main aerobic component while only a small number of the
      fecal specimens contain Escherichia coli and Streptococcus spp. None of the
      literature to date has stated that Streptococcus spp. do not belong to the
      autochthonous fecal or intestinal flora of an avian species. Clostridium
      perfringens cannot be isolated. The identifiable fecal flora of captive
      Capercaillies consists of many species with high colony numbers. Almost all fecal
      specimens contain Escherichia coli and various Bacillus spp. Streptococcus spp.
      can be isolated frequently, other enterobacteriaceae and Clostridium perfringens
      are present. The results of the examinations for fungi and parasites only differ
      slightly from those in wild birds.

PMID- 8284962
TI  - Feed-induced lectins in piglets. Feed-induced lectins and their effect on post
      weaning diarrhoea, daily weight gain and mortality.
AB  - The effect on various biological variables of a special weaner feed (FD) with the
      capacity to induce endogenous synthesis of feed induced lectins (FIL), and a
      commonly used commercial diet (CD) was evaluated in 891 piglets in four different
      experiments. The FD diet was found to induce a high activity of FIL (FIL = 0.94
      +/- 0.03 units/ml. blood), as compared to CD (FIL < 0.20 units/ml. blood). The
      FIL values did not decrease after weaning. The incidence of diarrhoea in piglets
      fed FD 0-14 days post-weaning was 12 +/- 5 per cent, as compared to 41 +/- 9 per
      cent in the CD group, the difference being significant. Daily weight gain 0-35
      days after weaning was 67 +/- 15 grams greater in the FD group than among those
      fed CD. The consumption of FD was double that of CD in the period before weaning
      (at 5 weeks), and some 40 per cent more in the postweaning period up to 9 weeks
      of age.

PMID- 8284963
TI  - Prevalence of antibodies to Streptococcus bovis serotype 1 in racing pigeons.
AB  - Indirect ELISA techniques for the detection of antibodies to S. bovis serotypes
      1, 2 and 3 in pigeon plasma were developed. Whole formaldehyde-inactivated
      bacteria were used as coating antigens. Bound antibodies were detected with
      peroxidase-conjugated rabbit anti-pigeon serum and OPD and H2O2 as chromogen and
      substrate, respectively. ELISA was used to determine the prevalence of antibodies
      to S. bovis serotype 1 in healthy Belgian racing pigeons. Antibodies were
      demonstrated in 83 (= 37%) of 225 samples tested. Results indicate that pigeons
      may build up plasma antibodies in the absence of clinical signs resembling
      septicaemia.

PMID- 8284964
TI  - Comparison of the restriction patterns of equine herpesvirus (EHV-1) strains
      isolated for eight years in France.
AB  - The equine herpes viruses strains (EHV) isolated from organs of aborted foetuses
      or from nasal swabs have been analysed by comparison of their restriction
      endonucleases patterns using two enzymes, Bam HI and Pst I. The majority of the
      clinical samples came from the west part of France ("Normandie") after abortions
      or respiratory disorders. All the viruses isolated were EHV-1 strains whose
      patterns show considerable homogeneity although some differences can be
      described. The genomic DNAs of the same twenty strains have been digested by the
      Pst I enzyme, which induced a great number of restriction fragments. It allows a
      more precise epidemiological study between strains isolated in the same studs
      with different Bam HI patterns or between strains with identical Bam HI profiles
      but with distinct respiratory or abortigenic pathogenicity. No strain isolated
      from aborted foetuses or nasal swabs presented the vaccinal pattern.

PMID- 8284965
TI  - Effect of selected antibiotics on Staphylococcus aureus present in milk from
      infected mammary glands.
AB  - Milk from a mammary gland infected with Staphylococcus aureus Newbould 305 was
      collected and dispensed into sterile tubes. Selected antibiotics were added at 2,
      4, or 32 times the MIC, and the percentage survival of S. aureus at various times
      through 24 h after addition of each antibiotic was determined. Percentage
      survival of the same S. aureus strain grown in vitro and added to 1) Mueller
      Hinton broth and 2) ultrahigh temperature pasteurized milk with the same
      concentration of antibiotics was also determined. Percentage survival observed
      after 24 h in milk from the infected quarter at 2, 4, and 32 times MIC,
      respectively, were: penicillin: 12, 9.4, and 13%; cephapirin 43, 50, and 30%;
      erythromycin: 120, 95, and 82%; pirlimycin: > 1000, 148, and 38%; tilmicosin: >
      1000, > 1000, and 9%; ciprofloxacin: 458, 6, and 3%; norfloxacin: 40, 10, and <
      1%; rifampicin: < 1, < 1, and < 1%; and novobiocin: 20, 41, and 5%. By
      comparison, percentage survival observed after 24 h for in vitro grown S. aureus
      tested in Mueller-Hinton broth at 2, 4, and 32 times MIC, respectively, were < 1%
      for penicillin, cephapirin, pirlimycin, ciprofloxacin, norfloxacin, and
      rifampicin, and < 10% for erythromycin, novobiocin, and tilmicosin. UHT milk had
      minimal effect on percentage survival compared to Mueller-Hinton broth for S.
      aureus 305 when tested against penicillin or cephapirin. Increased survival was
      noted in UHT milk for erythromycin, pirlimycin, and tilmicosin at all antibiotic
      concentrations and for ciprofloxacin, norfloxacin, rifampicin, and novobiocin at
      2 times the MIC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284966
TI  - Course of infection and humoral immune reaction in calves infected orally with
      different Salmonella serovars.
AB  - 5 groups of five calves each were orally infected with the salmonella serovar S.
      agona, S. dublin, S. enteritidis, S. infantis or S. typhimurium. The course of
      infection and the humoral immune response against 5 antigen preparations of the
      homologous and the 4 heterologous salmonella serovars were monitored in each
      group. Antibodies against two different protein antigens and against two
      differently prepared LPS antigens were determined by ELISA and the level of H
      agglutinin was assessed by micro agglutination test. All 5 serovars proved to be
      virulent for calves. The specificity of antibodies produced following the
      infection are not always consistent with the Kauffmann-White scheme. There was a
      relation of age and strain for infection on immune response, whereas the severity
      of infection did no correlate with an increase of antibody production. The
      serological tests used were good for investigation of a defined host-parasite
      interaction but not satisfactory for serovar specific diagnosis of salmonella
      infection in cattle.

PMID- 8284967
TI  - Vaccination of chickens with live fowl pox (FP) vaccine in oil.
AB  - Live fowl pox (FP) vaccine was adjuvanted in oil just prior to the subcutaneous
      (SC) vaccination of one day old chicks and adult chickens. The birds were
      challenged by the wing web (WW) method and absence of "takes" were considered as
      protection. On 21 day post challenge, 90%-100% of the chicks or chickens were
      protected while on day 9 post challenge 60% were protected. Full protection of
      the live-in-oil adjuvanted vaccine is probably somewhat delayed as compared to
      protection endowed by the liquid vaccine. Incorporation of live FP vaccine in two
      different kinds of commercial Newcastle disease (ND) killed vaccine in oil, was
      shown to endow full protection following SC administration.

PMID- 8284968
TI  - Worldwide mortality changes from all causes and from cardiovascular diseases
      between 1968 and 1988.
AB  - The worldwide changes in mortality from 35 countries, between 1968 and 1988, have
      been analyzed in four age classes between 45 and 85+ years and in both sexes,
      together with years gained in life expectancy at age one between 1967 and 1990.
      The most important decreases have been seen in populations with important changes
      in life style, primarily nutritional, such as in East Asia, Australia, Finland,
      Austria, France, Switzerland, Portugal, Belgium, F.R.G. and Spain. Less
      beneficial changes were observed in Sweden and The Netherlands. Unsatisfactory
      changes were observed in Norway, Denmark and especially in the East European
      countries. The small increase in life expectancy at age one (+1.5 year) observed
      in Denmark between 1967 and 1990 was situated between that of the former German
      Democratic Republic and of Czechoslovakia, +1.6 and +0.3, respectively. However,
      marked differences exist among sexes and age classes. The changes obtained for
      all-cause mortality in the 75-84 years age class are better than in the 45-64
      years age class. All these observations cannot be explained by better medical
      treatment only and point towards nutrition as the most important causal factor.

PMID- 8284969
TI  - Nutrition and life expectancy of populations.

PMID- 8284970
TI  - Dietary fat intake and coronary heart disease in women.

PMID- 8284971
TI  - Nutrition and diabetes: the role of fat.

PMID- 8284972
TI  - Epidemiological aspects of dietary lipids and health--a review.

PMID- 8284973
TI  - Platelets and dietary prevention of coronary heart disease (CHD).

PMID- 8284974
TI  - Dietary fat and cancers of the colo-rectum and breast: a short review.

PMID- 8284975
TI  - On the importance of dietary fat. Conclusions from the Framingham Study.

PMID- 8284976
TI  - Antioxidants and risk of myocardial infarction. EURAMIC Study Group.

PMID- 8284977
TI  - The role of lipid peroxidation, antioxidants and pro-oxidants in atherosclerosis.

PMID- 8284978
TI  - Trans fatty acids in human nutrition.

PMID- 8284979
TI  - Methodological problems in nutritional epidemiology.

PMID- 8284980
TI  - Validation of nutritional studies for use in epidemiology.

PMID- 8284981
TI  - Nutrition in Hungary.

PMID- 8284982
TI  - Nutrition in China.

PMID- 8284983
TI  - Changing dietary patterns in Japan.

PMID- 8284984
TI  - Dietary fat intake in relation to apo E isoforms and body fat distribution in
      obese women.

PMID- 8284985
TI  - Quantification and physiological role of lipoprotein Lp(a).

PMID- 8284986
TI  - Nutrition and chronic disease--the viewpoint of WHO.

PMID- 8284987
TI  - Nutrition and health policy regarding fat consumption for U.S. population.

PMID- 8284988
TI  - Influencing the diet of populations: the Finnish experience.

PMID- 8284989
TI  - Hormonal profile in mild heart failure.
AB  - Neurohormonal activation is a fundamental component in the pathophysiology of
      congestive heart failure. In fact it represents a mechanism consecutive to
      cardiac dysfunction that favours the development of congestion and of further
      heart failure through vasoconstriction and water and salt retention. The time of
      onset and the mechanisms responsible for neurohormonal activation in heart
      failure are not defined. This brief article reviews this topic and summarizes the
      findings of studies that investigated the dynamic adaptations of hormonal
      mechanisms in the milder or initial stages of heart failure. An early
      characterization and detection of the abnormalities of the hormonal responses to
      salt or volume changes may be useful for a better comprehension and the treatment
      of the initial stage of the disease.

PMID- 8284990
TI  - Hemodynamic effects of nifedipine in patients with asymptomatic aortic
      regurgitation: evaluation by Doppler echocardiography.
AB  - Nineteen asymptomatic patients affected by isolated chronic aortic regurgitation
      received 20 mg of nifedipine sublingually: the acute hemodynamic effects of
      nifedipine were evaluated by combined cross-sectional and Doppler
      echocardiography. To assess variations in the regurgitant flow volume, the flow
      volume across the mitral and aortic valves was calculated as the product of
      velocity-time integral multiplied by the orifice valve area. Flow volume across
      these valves represented the total stroke volume, and forward stroke volume,
      respectively: the regurgitant volume was obtained by calculating the difference
      between total and forward stroke volume. Nifedipine induced a redistribution of
      the two components of the total left ventricular stroke volume: regurgitant
      stroke volume decreased from 57 +/- 22 ml/beat to 46 +/- 21 ml/beat (P < 0.002),
      while forward stroke volume increased from 83 +/- 12 to 93 +/- 15 ml/beat (P <
      0.0005), as a consequence of the reduction in systemic vascular resistance from
      1513 +/- 378 to 1092 +/- 307 dynes.sec.cm-5 (P < 0.0001). The reduction of
      regurgitant volume was due to either a 24.8% decrease of the aortic-left
      ventricular mean pressure gradient during diastole (P < 0.008) or a 6% decrease
      of the diastolic time interval (P < 0.04). The effect of these acute changes on
      left ventricular loading was to induce a reduction in oxygen consumption which
      was expressed by a decrease in the double product (from 10176 +/- 1767 to 9444 +/
      1559 mmHg.beats/min; P < 0.002), in spite of a significant increase in heart
      rate. This study, therefore, shows the beneficial acute hemodynamic effect
      induced by nifedipine in asymptomatic patients affected by chronic aortic
      regurgitation and shows that Doppler-echocardiography is a useful instrument for
      the evaluation of hemodynamic changes immediately after the administration of
      drugs.

PMID- 8284991
TI  - Influence of left ventricular hypertrophy on the diastolic performance in
      hypertensive patients and in athletes.
AB  - The aim of the study was to investigate whether the aetiology of left ventricular
      hypertrophy (LVH) is related with distinct abnormalities of left ventricular
      diastolic performance. METHODS: thirty patients with mild to moderate essential
      hypertension (15 without echocardiographic evidence of LVH and 15 with LVH) and
      15 athletes with LVH were studied. Control group comprised 10 normotensive
      subjects. By means of echocardiography, the dimensions (EDD, ESD) the wall
      thickness (IVST, PWT) and their ratio (IVST/PWT), the ejection fraction (EF), the
      mass (LVM) and the index mass (I mass) of the left ventricle (LV) as well as the
      dimension (LA) and the emptying index (LAEI) of the left atrium were measured.
      From the first derivative of the apexcardiogram the a/b and ef/ZN indices were
      estimated. RESULTS: in hypertensive patients, with or without LVH, a decrease of
      LAEI and increases of a/b and ef/ZN indices were found, compared to normotensive
      subjects. In contrast, no significant differences were observed between athletes
      with LVH and normotensive subjects. CONCLUSIONS: in hypertensive patients the
      diastolic performance of the LV, as derived from the alterations of the indices
      LAEI, a/b and ef/ZN appears to be impaired at an early stage. This alteration may
      be related with the increased afterload and diminished diastolic compliance of
      the LV. In contrast, LV diastolic performance in athletes, even in the presence
      of LVH, is not affected possibly because fibrosis of the hypertrophic myocardium
      is less pronounced not affecting LV diastolic compliance.

PMID- 8284992
TI  - [Comparison of surgical and radioactive synovectomy in various disorders of the
      knee joint].
AB  - The authors evaluate after an interval of 1-20 years the long-term results of
      surgical synovectomy in 454 patients and radioactive synoviorthesis in 528
      patients performed at the First Orthopaedic Clinic, Medical Faculty, Comenius
      University and Faculty Hospital in Bratislava and at the Orthopaedic and
      Traumatological Clinic of the Medical Faculty in Martin in 1969-1991. The most
      frequent diagnosis in surgical synovectomy is rheumatic synovitis in radioactive
      synovectomy arthrotic synovitis (47.6% and 68.6%). The authors evaluate both
      methods of synovectomy according to Aidem-Baker and compare the results of the
      two methods. They found significantly more very good and good results after
      surgical synovectomy (54.8% and 33.5%) as compared with radioactive
      synoviorthesis (15.5% and 38.0%). Conversely they found significantly more
      satisfactory and poor results in radioactive synoviorthesis (29.1% and 17.4%)
      than after surgical synovectomy (8.8% and 2.9%) which comprise patients
      relatively satisfied with this procedure and who do not agree with other
      procedures.

PMID- 8284993
TI  - [Structure of compact bone and types of stress in the long bones in humans].
AB  - The authors elaborated a new macroscopic method which made it possible to analyze
      the orientation of osteons in the entire diaphysis. All long bones of the human
      extremities were thus analyzed. In each bone the osteons are arranged in a
      specific pattern but according to a uniform plan. Most of them are oriented in an
      oblique direction and are arranged as two helices of opposite directions located
      on opposite sides of the bone. The two fields are separated by a sharp
      borderline. Biomechanical analysis revealed that the orientation of the osteons
      is consistent with the direction of the maximal principal stress which depends on
      the normal and torsional stress to which the bone is exposed. From the
      orientation of osteons the authors derived ex post the mode of dominant loading
      of all long bones: the femur is exposed to bending in the medial direction and to
      outer rotation, the tibia is exposed to bending in dorsal direction and to inner
      rotation. The humerus is bent in the medial direction, the radius in the dorsal
      one. Both these bones are exposed to loading in inner rotation. In the ulna and
      fibula the mode of stress could not be assessed by the authors' method. The
      results are summarized in two diagrams which indicate the orientation of osteons
      and the way in which the long bones in man are exposed to load. The authors
      discuss the theoretical and practical impact of these findings.

PMID- 8284994
TI  - [Results of reconstructive surgery in fractures of the proximal humerus].
AB  - In treatment of comminuted dislocation fractures of the proximal humerus the most
      serious therapeutic problem still remains the 6th group of Neer's classification,
      in particular fractures with four fragments and with a completely dislocated and
      devitalized head. The authors present in a retrospective study an overall
      comparison of results assembled in 30 patients (and 19 checked patients resp.)
      who were operated by the technique of anatomical reconstruction (13 and 8
      patients resp.) or by the authors own technique of non-anatomical reconstruction
      (17 and 11 patients resp.), all operated on account of comminuted dislocation
      fractures of the proximal humerus at the orthopaedic clinics of the First and
      Third Medical Faculty, Charles University, Prague in 1976-1988. Analysis of the
      results of the checked patients made the authors draw the following conclusions:
      1. Fractures of the proximal end of the humerus is a relative frequent injury, in
      particular in the elderly. About 20% of these injuries call for surgical
      treatment. 2. In all non-anatomical reconstructions the mobility is very
      restricted in particular exorotation, in anatomical reconstructions the
      restriction is much smaller. 3. In all patients operated by the technique of non
      anatomical reconstruction within three years necrobiotic reconstruction of the
      fragment of the head occurred which is the greater, the larger the fragment of
      the head which was preserved. 4. The result of the reconstruction depends on the
      preservation of nurture of the fragment of the head and on selection of an
      adequate technique of osteosynthesis. 5. In anatomical reconstructions the most
      frequent complication was loosening of the osteosynthetic material, a varus
      position of the head and pseudoarthrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8284995
TI  - [The Strayer surgical technic as the basic operation for treatment of pes equinus
      in cerebral palsy].
AB  - The authors describe the technique of Strayer's operation (gastrocnemius
      recession) in the spastic form of cerebral palsy and draw attention to its
      indications, possible combinations with other operations and technical errors
      associated with its implementation. They evaluate 644 operations made by
      Strayer's method. In 361 regularly followed-up patients they evaluate from the
      long-term aspect combined operations of the lower extremities (which form a
      functional unit), using as a basis their own locomotor and position standards.
      They emphasize the necessity of a correct strategy, i.e. selection and sequence
      of surgical procedures. They recommend Strayer's operation (gastrocnemius
      recession) as the basic operation in pes equinus spasticus and in genu flectum
      spasticum. In the conclusion they present their own modification of Strayer's
      operation elaborated by the first author.

PMID- 8284996
TI  - [Genu flectum in cerebral palsy, elongation of the flexors of the knee joint and
      our modification].
AB  - The authors evaluate the results of prolongation of the flexors of the knee joint
      in 175 patients with a flexed position of the knee joint associated with the
      spastic form of cerebral palsy. They draw attention to the interrelationship of
      the position of the lower extremities in the area of the sole, knee and hip joint
      and emphasize the necessity of correct assessment of primary contractures. They
      emphasize also the evaluation of correct concurrent function of flexors and
      extensors of the knee and their balanced functioning. The authors prefer a single
      surgical operation in combined affections of the lower extremities to the system
      of so-called minor steps. They emphasize the importance of postoperative
      rehabilitation and prosthetic support. In the authors' opinion surgery of the
      knee joint in manifestations of cerebral palsy on the lower extremities is the
      most controversial area associated with the highest percentage of failures and
      complications. Contrary to data in the literature, they refute the necessity of
      capsulotomy of the knee joint and recommend their own modification how to treat
      severe forms of genu flectum spasticum.

PMID- 8284997
TI  - [Aggressive chondroblastoma].
AB  - The authors report three observations of rather extensive aggressive
      chondroblastoma and draw attention to difficulties of histological diagnosis,
      which result out of a less typical histological picture, in which signs of
      differentiation into cartilaginous tissue may be missing. Differential diagnosis
      may be facilitated by proper recognition of the cytologic character of
      chondroblasts by the positivity of S-100 protein, and by proving characteristic
      properties of chondroblasts in electronmicroscopic examination. In treating this
      type of tumors an increased risk of local recurrence (in one of our patients) and
      aggressive behaviour to surrounding tissues should be considered, exceptionally
      pulmonary metastases may develop, as was the case in one of our presented
      patients.

PMID- 8284998
TI  - [Hallux valgus--the Dega surgical technic].
AB  - The author gives an account of one possible approach to the surgical treatment of
      valgus deformities of the toe. He corrects by the described subcapital wedge
      shaped osteotomy of the first metatarsal bone the valgus deviation of the toe in
      the first metatarsophalangeal joint and at the same time he remodels the
      metatarsal arch of the foot. The surgical procedure is described and the results
      of operations, incl. complications, are evaluated. During check-up examinations
      some 85% of the patients found the results of the operation satisfactory. 13.5%
      of the patients reported pain when burdening the extremity. 12% of the patients
      reported difficulties with selection of footwear. Objective examination revealed
      in 9.5% of the patients revalgization.

PMID- 8284999
TI  - [Selection of treatment in femoral shaft fractures].
AB  - It is not possible and seems not reasonable to treat all kinds of femoral shaft
      fractures in the same way. Any type of osteosynthesis has its own advantages and
      disadvantages. The decision towards an operative procedure and the application of
      a special method depends on the individual situation of the patient and on the
      familiarity and experience of the orthopedic surgeon with the different available
      procedures. Single fractures, shaft fractures in combination with jointnear
      lesions, fractures in polytraumatized patients require a differentiated approach.
      Doubtless, nowadays the trend to treat all femoral shaft fractures by i.m.
      nailing is obvious. But it seems that there still exist a lot of indications
      where the plate or an external fixation can be used with remarkable advantages.

PMID- 8285000
TI  - [A brain injury caused by a fragment from a soda water carbon dioxide cartridge].
AB  - The authors present a report on the treatment of a female patient with a brain
      injury caused by a splint from an exploded sparklet used for making soda water.
      The rare occurrence of gunshot wounds in peace time leads to embarrassment as
      regards treatment of patients with this type of injury. It was found that in
      gunshot wounds of the head and brain it is necessary to revise the pathway of the
      splint after craniotomy, remove the foreign body, bone fragments and debris, then
      close carefully the opening in the dura mater, remove the margins of the bone
      contaminated with the object which caused the injury and stitch the skin. The
      authors draw attention to difficulties associated with localization of the
      foreign body in the pathway of the splint and to the possible use of peroperative
      two-dimensional ultrasonography.

PMID- 8285001
TI  - [Intrapelvic migration of a total hip prosthesis in rheumatoid arthritis].
AB  - The authors discuss the risk of mechanical loosening and protrusion of a cemented
      endoprosthesis of the hip joint after operation which is one of the few
      possibilities of palliative treatment in patients with rheumatoid arthritis. They
      deal in particular with specific features of surgical approaches whereby they
      select a modified method described by Eftekhar which makes it possible to resolve
      even severe grades of intrapelvic migration of the socket of a total
      endoprosthesis. The authors discuss possible complications which can be prevented
      if the relationship of intrapelvic structures to the protruded prosthesis is
      elucidated before operation. In a group of 1268 patients operated there were
      three with intrapelvic migration of a total endoprosthesis of the hip joint.

PMID- 8285002
TI  - [Treatment of acetabular fractures].
AB  - The authors present an account of 85 patients with fractures of the acetabulum
      treated at the Orthopaedic Clinic, Faculty Hospital Plzen in 1985-1991. The
      fractures are classified according to Lettournel-Judet. The authors investigated
      associated injuries which prolong the interval between injury and operation as
      well as the correlation between the mechanism of injury and the patient's age and
      the incidence of injuries in different months of the year. For indication for
      operation the quality of reposition evaluated by computed tomography is
      essential. The authors analyze the length of the interval between injury and
      operation, administration of antibiotics and anticoagulants. As to early
      complications, they pay attention in particular to bronchopneumonia, infection
      and thromboembolic disease. The paper deals also with the most serious late
      complication--avascular necrosis--and the authors discuss the causes of its
      development as well as possibilities to influence it. The paper presents also
      results evaluating patients as regards their return to work, subjective
      evaluation of gait, pain of the joints and satisfaction with treatment. The case
      history is followed by discussion concerned with the importance of computed
      tomography, the surgical approach, importance of treatment of the sacroiliac
      complex, the development of heterotopic and ectopic ossifications and the
      essential time of relief of the operated joint. In the conclusion the authors
      summarize the basic principles of fractures of the acetabulum.

PMID- 8285003
TI  - [A sandwich-type hip joint socket with a ceramic lining].
AB  - The authors present a new type of sandwich socket with ceramic lining. Mechanical
      tests provide evidence that the submitted implant is very firm. It is a basic
      prototype from which cemented and non-cemented sockets of the hip joint will be
      derived. The authors use a 28 mm socket paired with a 28 mm head and 12/14 conus
      and 14/16 Euroconus. This means that the submitted socket is compatible with all
      types of cemented and non-cemented endoprostheses.

PMID- 8285004
TI  - Wave plate osteosynthesis as a salvage procedure.
AB  - The load axis of the curved-shaped proximal femur lies not inside, but outside
      the bone. Therefore high bending forces are acting, the medial cortex absorbing
      pressure, the lateral cortex absorbing tension. In a transverse fracture, a
      laterally applied plate will absorb the tensile stresses, the medial cortex the
      pressure forces. When medial butress due to bony defect is missing, the laterally
      applied plate is subjected to cycling bending and will undergo fatigue fracture.
      This dilemma is compensated by a wave-plate with bone graft: The compression
      forces are detoured to the lateral cortex and the plate is again subjected to
      tension. Furthermore since the plate is standing away from the bone, the plate
      does not disturb the blood supply at the fracture side and bone healing.

PMID- 8285005
TI  - [Personal experience with non-cemented femoral components in the Schenker total
      hip prosthesis].
AB  - Based on seven-year experience with non-cemented femoral components of total
      endoprostheses of the hip joint, type Schenker, the authors assume that their use
      is limited only to a small group of patients under 40 years of age, provided
      strict principles as regards precision of implantation are respected. The latter
      are discussed in the submitted paper.

PMID- 8285006
TI  - [Experience with non-cemented stems in Schenker hip prosthesis].
AB  - In 1986-1988 at the Orthopaedic clinic of the Institute for Postgraduate Medical
      Training 56 stems on non-cemented total endoprostheses of the hip joint type
      Schenker were implanted. The non-cemented stem was combined in all patients with
      a cemented socket Poldi. The endoprosthesis was indicated in particular in young
      patients in 59% in hip joints affected with secondary postdysplastic arthritis of
      the hip joint. The group was checked by Harris' method, the mean follow-up period
      in 1992 was 58 months. Of 36 followed up patients 21 operated patients reported
      pain in the area of the hip joint, 10 patients used analgetics. In nine patients
      reimplantation of the non-cemented Schenker stem was performed on account of
      aseptic loosening, in 11 patients the X-ray check revealed obvious signs of
      aspectic loosening associated with subjective complaints. The dependence of
      aseptic loosening on the quality of primary implantation is marked. In patients
      with perfect cortical contact of the stem aseptic loosening developed in 27% of
      the patients, in patients with inadequate cortical contact aseptic loosening was
      recorded in 80% of the operated patients. The general evaluation according to
      Harris comprised 42% excellent results, 30% good results, 14% satisfactory
      results and 14% poor results. This evaluation does not include patients who on
      account of pain and loosening of the femoral Schenker component were already re
      operated. Because of the considerable number of complications implantation of
      this type of prosthesis was discontinued at the authors' department.

PMID- 8285007
TI  - [Our method of arthrodesis of the wrist].
AB  - The authors emphasize the importance of a stable pain-free carpus for the
      function of fingers. Reflections on their own type of osteosynthesis are based on
      anatomical and biomechanical findings. They emphasize the functional concept of
      the central pillar of the wrist where maximum flexion and extension takes place.
      In this very line formed by the distal portion of the radius, os lunatum, os
      capitatum and the base of the third metacarpal bone they apply the splint. The
      splint is as compared with classical AO splints low (only 2.8 mm), L-shaped and
      in its cross section slightly convex dorsally. It follows thus the natural
      arching of the carpal and metacarpal bone and does not increase the tension of
      soft structures and the overlying skin. By the localization of oval openings it
      makes slight self-compression possible and ensures adequate, three-point fixation
      of the metacarpal region. The oval opening in the short branch of the splint
      serves location of the centre of the transverse section of the second metacarpal
      bone and ensures correct placement of the screw. It makes plastic operation of
      extensors possible which in rheumatic synovialis and destruction of the carpal
      bone are frequently impaired. The authors present the results of 21 operations.
      Adequate healing of bone was achieved in all patients, on average after 3.5
      months. In all the height of the carpal index (CHI) was increased and the hand
      grip improved. In nine patients they found rupture of the extensors and repaired
      it. In all instances they performed synovectomy and resection of the head of the
      ulna. Two patients have bilateral arthrodesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285008
TI  - [Diagnostic and therapeutic arthroscopy of the elbow joint].
AB  - The anatomical structure of the elbow joint makes arthroscopy markedly more
      difficult, as compared with the knee joint or shoulder. This is confirmed also by
      the small number of hithero published work. The limitation of inspection of the
      elbow joint ensues from the firm articular capsule and restricted intraarticular
      space. This leads to difficult manipulation of optical and other instruments in
      the limited visual field. The position of neurovascular structures in the
      vicinity of the surgical approach increases the demands of surgical technique.

PMID- 8285009
TI  - [Importance of tenotomy of the adductors in the treatment of cerebral palsy
      manifestations in the lower extremities].
AB  - The authors evaluate 303 tenotomies of adductors performed in patients with
      cerebral palsy (CP) in 1970-1992. They emphasize the correct diagnosis of
      adduction contracture of the hip joint and correct treatment, incl. early
      surgery, not only because of the influence of adductors on standing and gait but
      also on the development of the hip joint in children. The authors draw attention
      to the increased incidence of subluxations and luxations of the hip joint in
      recent years in children with CP who were not operated or where the muscular
      balance and contractures of the hip joint were not modified. They emphasize the
      fact that in children where tenotomy of the adductors was performed in time
      before the age of 8 years, with a single exception luxation did not develop. In
      the authors' opinion tenotomy at the age of cca 11 years is an essential
      operation but in view of the development of skeletal changes it is late. The
      authors recommend to pay increased attention to the problem of adductors in CP as
      regards diagnosis and technical aspects of the operation.

PMID- 8285010
TI  - [The importance of age in patients for the subsequent state of the growth
      cartilage lengthened by distraction epiphysiolysis].
AB  - The authors evaluated the state and behaviour of 18 growth cartilages in 16
      patients lengthened by the method of distraction epiphysiolysis in 1974 to 1991
      at the Clinic of Child Orthopaedics in Brno. Lengthening was performed in 8 boys
      and 8 girls in the area of the distal femur and/or proximal or distal tibia. The
      follow-up period of these patients was 2 to 8 years. The authors revealed that
      the bone age of the patient had a decisive effect on the state and behaviour of
      the lengthened epiphyseal growth plate. The mode and rate of release of the
      growth zone was the same, similarly as the rate of lengthening; despite this the
      patients could be divided into three defined groups: 1. The growth cartilage
      remained open, remained active and closed when the cartilages on the non
      lengthened side closed. The bone age was on average 8 years. 2. The growth
      cartilage was apparent for a certain period (2 or more years) but closed sooner
      than on the non-lengthened side. The mean bone age was 10.35 years. 3. The growth
      cartilage disappeared already during distraction epiphysiolysis. The mean bone
      age was 14.3 years. The authors conclude that assessment of the bone age in
      patients where lengthening of bones by distraction epiphysiolysis is planned is
      very useful as it makes it possible to predict with a high probability further
      behaviour of the epiphyseal cartilage after its lengthening and thus the need of
      possible revision.

PMID- 8285011
TI  - [Causes of corrosive mechanical defects in isoelastic endoprostheses].
AB  - Within the framework of evaluation of endoprostheses of the hip joint reoperated
      at the orthopaedic clinic of the Institute for Postgraduate Medical Training,
      Faculty Hospital Na Bulovce in Prague in the course of six years the authors made
      a more detailed analysis of the group of isoelastic POLDI endoprostheses which
      displayed obvious signs of corrosion. The specimens from this group were
      subjected to evaluation focused on corrosion, metallographic and fractographic
      evaluation. In impaired wires of isoelastic endoprostheses the fracture surfaces
      have a fatigue character where a corrosion fatigue mechanism may be assumed as
      well fracture with a dominant mechanical component of stress. From the analysis
      of corrosion ensues that the connections of the wire shank with the head of the
      endoprosthesis are affected by crevice corrosion, the revealed fractures and
      cracks are most probably associated with corrosion fatigue. The construction of
      isoelastic prostheses of this type is the cause of corrosion processes which lead
      to mechanical failure. This should be the reason to refuse them for patients of
      any age group.

PMID- 8285012
TI  - [The founder of modern trauma surgery, Prof. Lorenz Bohler (1885-1973)].

PMID- 8285013
TI  - [Discussion of the article by K. Urban, J. Stehlik: Initial clinical experience
      with bioactive BAS-O glass-ceramic material].

PMID- 8285014
TI  - A case of multiple myeloma with nuclear hypersegmentation after MP/VAD/VCAP-IFN
      therapies with a good prognosis.

PMID- 8285015
TI  - Gradual correction of leukocyte alkaline phosphatase in chronic myelocytic
      leukemia after interferon-alpha.

PMID- 8285016
TI  - Intermittent claudication as the presenting symptom in primary amyloidosis.

PMID- 8285017
TI  - Megadose methylprednisolone for idiopathic thrombocytopenic purpura.

PMID- 8285018
TI  - Recombinant erythropoietin in myelodysplastic syndromes: whom to treat and how?
      More questions than answers.

PMID- 8285019
TI  - Subcutaneous recombinant human erythropoietin for the treatment of anemia in
      myelodysplastic syndromes.
AB  - Recombinant human erythropoietin (rhEPO) was administered subcutaneously to 13
      anemic (Hb < 10 g/dl) patients with myelodysplasia (MDS). rhEPO was given 3 times
      a week at doses of 75-250 U/kg body weight, over a maximum period of 24 weeks.
      Five patients (38%) showed a response to rhEPO treatment. rhEPO was well
      tolerated and without relevant side effects throughout the study. All responding
      patients had low but detectable pretreatment circulating erythroid progenitor
      cells (BFU-E) and the response to rhEPO was associated with a significant
      increase in BFU-E (p < 0.01); concentrations of serum transferrin receptor (TfR)
      also consistently rose in all responding patients. Baseline erythropoietin (EPO)
      concentrations did not significantly differ between responders and nonresponders,
      although 4 out of the 5 responders had relatively low levels of EPO. In
      conclusion, subcutaneous rhEPO administration appears to be an effective
      treatment of anemia in a substantial subset of patients with MDS. Relatively low
      baseline EPO concentrations, detectable pretreatment circulating BFU-E and an
      early increase in the serum concentrations of TfR seem to be criteria for
      predicting response to rhEPO in patients with MDS.

PMID- 8285020
TI  - Recombinant human erythropoietin in patients with myelodysplastic syndrome and
      myelofibrosis.
AB  - In a dose titration study we tested the efficacy and tolerance of recombinant
      human erythropoietin (rhEPO) in 10 patients with myelodysplasia (MDS) and 2
      patients with idiopathic myelofibrosis. Patients with a haemoglobin level < 100
      g/l were treated as out-patients for 12 weeks with daily doses ranging from 30
      U/kg body weight (BW) up to 240 U/kg BW in non-responders. Of the 10 patients
      with MDS, 6 were suffering from refractory anaemia with sideroblasts (RAS) and 4
      from refractory anaemia with an excess of blasts. The median age was 73 years
      (range 41-81). Two patients with RAS responded with a rise in haemoglobin
      concentration to > 130 g/l. They had not been transfusion-dependent prior to
      treatment. Both patients had relatively low serum concentrations of
      immunoreactive EPO. There was neither a rise in haemoglobin nor a reduction in
      transfusion dependence in any of the other patients. It may be concluded that
      rhEPO is possibly effective in a subgroup of MDS patients where the disease is
      less advanced. None of the transfusion-dependent patients benefited.

PMID- 8285021
TI  - Interferon plus glucocorticoids as intensified maintenance therapy prolongs tumor
      control in relapsed myeloma.
AB  - Interferon-alpha-2b (IFN) has been demonstrated to prolong remission duration and
      survival in responding multiple myeloma (MM) patients. The aim of this study was
      to intensity maintenance therapy adding glucocorticoids (GLU) to the standard IFN
      therapy. Twenty-eight relapsed MMs with stable disease or response after
      conventional chemotherapy received IFN+GLU. The treatment included 3 megaunits of
      IFN 3 times a week continuously until relapse, plus 4 days pulsed high-dose
      dexamethasone (40 mg/day for 4 days every 28 days for 6 consecutive months every
      12 months) in patients < 70 years, or oral prednisone (PDN, 50 mg 3 times a week)
      in patients > 70 years, both until relapse. Conventional chemotherapy induced a
      response in 12/28 MMs. For all patients the actuarial median progression-free
      survival from relapse was 24 months and the survival from relapse 42 months with
      no difference between responding and nonresponding patients. The first duration
      of tumor control, i.e. the interval from diagnosis to first relapse, was shorter
      than the period between first and second relapse in 11/28 patients (40%).
      Toxicity was mild and oral PDN significantly increased the subjective
      tolerability of IFN. These findings indicate that IFN+GLU after induction
      chemotherapy may prolong the duration of tumor control in relapsed MM.

PMID- 8285022
TI  - Effects of tumor necrosis-factor on primary human leukemia cells: ultrastructural
      changes.
AB  - We investigated the ultrastructural effects of recombinant tumor necrosis factor
      alpha (TNF) on primary leukemia cells of 8 patients (4 cases of acute myelogenous
      leukemia and 4 cases of chronic myelogenous leukemia) as well as on bone marrow
      cells of 1 normal control. The cells were kept in liquid culture for up to 92 h
      in the presence of up to 10,000 U/ml of recombinant human TNF without adding
      colony-stimulating factors. Under these conditions the concentration of viable
      leukemic cells decreased by 14 to 53%, compared to control cultures. In acute
      myelogenous leukemia, all cases to some degree developed an enlargement of
      mitochondria; in 2 cases prominent cytoplasmic processes, and in 2 cases
      cytoplasmic vacuoles were observed. In chronic myelogenous leukemia, an
      enlargement and deformation of all cell types was observed to varying degrees. In
      the normal bone marrow sample only minor cytoplasmic changes occurred. In all
      cultures apoptotic changes were rarely observed and--if present--were observed
      also in cultures without TNF. When the DNA of leukemic cells treated with TNF was
      separated on agarose, no fragments characteristic of apoptosis were visible. Our
      results demonstrate that TNF does not induce direct cytotoxicity or apoptosis in
      acute or chronic myeloid leukemias and are compatible with the notion that some
      leukemic cells may be activated or stimulated by TNF. The mitochondrion appears
      to be one of the primary targets of TNF. Electron microscopy is useful for
      monitoring the changes induced by TNF.

PMID- 8285023
TI  - Immunohistochemical characteristics of monocytoid B cell lymphoma, mantle zone
      lymphoma, small lymphocytic lymphoma (or B chronic lymphocytic leukemia), and
      hairy cell leukemia.
AB  - Biopsy specimens obtained from 2 patients with monocytoid B cell lymphoma, 7 with
      mantle zone lymphoma, 7 with small lymphocytic lymphoma or B chronic lymphocytic
      leukemia, and 6 with hairy cell leukemia were investigated using an
      immunohistochemical method to detect their immunophenotypic characteristics.
      Periodate-lysine-paraformaldehyde-fixed frozen biopsies from the lymph node,
      peripheral blood, bone marrow, spleen, tonsil, lung, and stomach were studied.
      Monocytoid B cell lymphoma exhibited the immunophenotype of surface(s) IgD-/DRC-1
      /Leu-1(CD5)-/Leu-M5(CD11c)-, +/- on the neoplastic cells or neoplastic lesions,
      mantle zone lymphoma exhibited that of sIgD+/DRC-1++/Leu-1-,+/Leu-M5-, small
      lymphocytic lymphoma or B chronic lymphocytic leukemia that of Leu-1+/sIgD-,+sIgD
      ,+/DRC-1- > +Leu-M5-, and hairy cell leukemia that of Leu-M5++/sIgD- >> +/Leu-1-
      >> +/DRC-1-. We therefore suggest that these four types of lymphomas can be
      differentiated by a combination of anti-sIgD, DRC-1, Leu-1, and Leu-M5 monoclonal
      antibodies based on their immunophenotypic characteristics.

PMID- 8285024
TI  - Cancer morbidity rates of children from the vicinity of the nuclear power plant
      of Wurgassen (FRG).
AB  - The morbidity rates from neoplastic disease have been studied in children below
      the age of 15 years, residing at the time of their diagnosis within a diameter of
      25 km of the nuclear power plant of Wurgassen (FRG). A total of 42 patients were
      registered between the years of 1980 and 1988: 15 patients with neoplasms of the
      hematolymphopoietic system, 14 neoplasms of the central nervous system (CNS), and
      13 with solid tumors outside of the CNS. The data show that children living in
      the vicinity of this nuclear power plant do not have an increased risk of
      developing neoplastic disease, as compared to the entire pediatric population of
      the FRG. However, a tendency for an elevated risk, not reaching the level of
      statistical significance, cannot be fully excluded.

PMID- 8285025
TI  - Iron deficiency anemia: recovery from in vitro oxidative stress.
AB  - Red blood cells in iron deficiency anemia (IDA) have a decreased activity of
      essential antioxidant enzymes. The present study examined the effect of in vitro
      exposure to oxidative agents in IDA cells and their recovery capacity. Red cells
      of 26 IDA patients and 10 healthy subjects were examined. Cells of IDA patients
      had higher levels of reduced glutathione (GSH), and normal methemoglobin and
      malonyldialdehyde (MDA) levels. Exposure to butyl hydroperoxide revealed a dose
      dependent sensitivity in IDA cells, with extensive GSH depletion and increased
      MDA levels. These changes were partially reversible by incubation with
      dithiothreitol. Exposure to phenazine methosulfate, to produce intracellular
      superoxide ions, resulted in moderate GSH depletion and methemoglobin production.
      IDA cells were more sensitive than control cells to high concentrations of this
      substance. This effect was further augmented by preincubation with a superoxide
      dismutase inhibitor. Our data demonstrate that IDA cells are more susceptible to
      oxidation but have good capacity for recovery.

PMID- 8285026
TI  - Early community health nursing in Alberta.

PMID- 8285027
TI  - Nursing: a dying art?

PMID- 8285028
TI  - Life after layoff--what really happens.

PMID- 8285029
TI  - Home care--1993.

PMID- 8285030
TI  - Tax and the travelling nurse--eight quick tax tips.

PMID- 8285031
TI  - Task force on direct access to services provided by registered nurses.

PMID- 8285032
TI  - New R.N.--a wonderful career? A personal view.

PMID- 8285033
TI  - Health care in Alberta: a futuristic perspective.

PMID- 8285034
TI  - Revenge of the laid off nurse.

PMID- 8285035
TI  - AARN position statement on the utilization of auxiliary health care workers in
      the delivery of health care.

PMID- 8285036
TI  - Controlling urinary incontinence. Interview by Patricia Marck.

PMID- 8285037
TI  - Analysis of viral infection in patients with IgA nephropathy.
AB  - We investigated viral infections in the tonsils, pharynx and renal tissues of
      patients with IgA nephropathy using cell culture, polymerase chain reaction (PCR)
      and immuno-fluorescent techniques, and measured antibody titers against numerous
      types of viruses. Neutralization tests found no significant inhibition of growth
      of adenovirus-1, 2, 3, 4, 5, 6, 7, 11 or 19, Coxsackie virus-A7, A9, A16, B1, B2,
      B3, B4, B5 or B6, or RS virus. Swabs of the oral cavity of patients with IgA
      nephropathy were cultured with Hel cells, MDCK cells, FL cells, BHK-21 cells and
      RD-18S cells. No cytopathic effect was detected in any of these cell cultures. We
      failed to detect the presence of herpes simplex virus-1 and -2, varicella-zoster
      virus, cytomegalovirus and Epstein-Barr virus (EBV)-1 and -2 in tonsils, renal
      tissues and mouthwashings from patients with IgA nephropathy. On the other hand,
      EBV alone was detected with the PCR technique, in mouthwashings from 6 out of 14
      patients with IgA nephropathy (42%). Immunohistological and serological analyses
      were done to examine the relationship between EBV and IgA nephropathy. No
      evidence was obtained that EBV-infected B lymphocytes were producing IgA. It
      seems unlikely that the viral infections examined in this study play a
      significant role in the pathogenesis of IgA nephropathy.

PMID- 8285038
TI  - Reconstitution of immunological imbalance in SCID mice given tonsillar
      mononuclear cells from patients with IgA nephropathy.
AB  - IgA nephropathy (IgAN) is thought to be mediated by the glomerular deposition of
      circulating immune complexes containing IgA as the major antibody component.
      Tonsillitis often precedes IgAN, and tonsillectomy is an efficient treatment of
      IgAN. Thus, the tonsil may cause initial and/or progressive events leading to
      IgAN. To determine the pathological features of tonsillar lymphoid cells, we
      transferred tonsillar mononuclear cells from IgAN patients to SCID mice. Although
      human IgG-, IgM- and IgA-positive cells were detected in the spleens of SCID-Hu
      mice, they failed to reproduce the increase in serum IgA level and glomerular
      deposition. These results suggest that other factors are needed for the
      progression of IgAN.

PMID- 8285040
TI  - Chronic tonsillitis and IgA nephropathy. Clinical study of patients with and
      without tonsillectomy.
AB  - To determine whether tonsillectomy is a significantly effective treatment in the
      clinical course of IgA nephropathy, we did a comparative study on 50 patients
      with IgA nephropathy and chronic tonsillitis. We divided the patients into two
      groups: 35 patients with and 15 without tonsillectomy (control group). With or
      without tonsillectomy, renal function became progressively worse during the
      follow-up period in most patients with a serum creatinine level of > 1.4 mg/dl at
      the time of renal biopsy. In patients with a serum creatinine level of < or = 1.4
      mg/dl, renal function remained normal in all subjects with tonsillectomy, but
      worsened in 3 patients out of 13 without tonsillectomy. Improvement in
      proteinuria/hematuria was found more frequently in the tonsillectomized group
      than in the controls. Furthermore, the serum IgA level was significantly reduced
      after tonsillectomy, especially in patients showing improvement. From these
      results we conclude that tonsillectomy was effective for patients with IgA
      nephropathy complicated by tonsillitis when the operation was performed before
      deterioration of renal function.

PMID- 8285039
TI  - Effect of and indication for tonsillectomy in IgA nephropathy.
AB  - Although more than 20 years have passed since the initial report of IgA
      nephropathy, the etiology of this disease is still unclear. Some reports suggest
      that the tonsil is an important etiological factor. We performed tonsillectomy on
      26 patients with IgA nephropathy associated with chronic tonsillitis, and
      followed up the patients for two years after the operation to evaluate its
      clinical effect on this disease. Twelve patients (efficacy rate 46%) showed
      distinct improvement in urinary findings after the operation, although the
      efficacy rate went down as renal injury advanced. Serum IgA levels decreased
      significantly after the operation both in patients who improved and in those who
      did not; the decrease was especially evident in patients who had high levels of
      serum IgA before tonsillectomy. In 4 patients who improved, the level of
      circulating immune complex (CIC) was extremely high before, and decreased
      significantly after, the operation. One patient suffered renal failure three
      years after tonsillectomy. When renal injury has advanced to the clinically
      apparent degree, as occurred in this patient, tonsillectomy is absolutely
      contraindicated. In reaching a decision as to whether tonsillectomy is indicated
      in mild cases, the change in the number of erythrocytes in urinary sediments may
      be a sensitive parameter of the tonsillar provocation test.

PMID- 8285042
TI  - Clinicopathological study of the effectiveness of tonsillectomy in IgA
      nephropathy accompanied by chronic tonsillitis.
AB  - Tonsillectomy is often effective in reducing proteinuria in patients with IgA
      nephropathy (IgAN), which might otherwise lead to renal failure. Twenty-eight
      patients with IgAN accompanied by chronic tonsillitis were observed for more than
      2 years after tonsillectomy and studied clinicopathologically. Tonsillectomy was
      effective in 17 patients (effective group), but not effective in 11 (noneffective
      group). Many patients in the effective group showed mild proteinuria, whereas
      proteinuria of 1 g/24 h or higher was found in a few cases. In comparison with
      the noneffective group, the levels of serum IgA, polymeric IgA and circulating
      immune complex (CIC) in the effective group were significantly higher prior to
      tonsillectomy. Histopathologically, there was only a slight increase in mesangial
      cells and matrixes in the effective group compared with the noneffective group,
      and global glomerular sclerosis, small glomerular crescents and interstitial
      scarring were seldom found. Rupture of the glomerular basement membrane (GBM)
      occurred more frequently in the noneffective than in the effective group. In a
      study of IgA subclasses in the mesangial area of the glomerulus, IgA1 was
      predominantly stained in the effective group.

PMID- 8285041
TI  - Expanded primary T nodules in the palatine tonsils from patients with IgA
      nephropathy.
AB  - We designed a study to investigate the morphological expression of immune
      responses in the palatine tonsils from patients with IgA nephropathy. To
      distinguish between the histological characteristics of the tonsils in habitual
      tonsillitis (47 patients) and IgA nephropathy (11 patients), we studied the T
      nodules, B-lymphoid follicles, germinal centers, areas of mixed T and B
      lymphocytes, lacunar epithelium and connective tissues; then we compared patients
      with habitual tonsillitis and IgA nephropathy. The T nodules in patients with IgA
      nephropathy were enlarged, and this change was not accompanied by atrophy of B
      lymphoid follicles. Morphologically, primary T nodules were predominant. In
      reactive lymph nodes, T nodules generally play an important role in the extra
      follicular maturation of stimulated B lymphocytes into Ig-secreting plasma cells.
      Therefore the enlarged primary T nodules remind us that this maturation may occur
      more frequently in the tonsils of patients with IgA nephropathy than in those
      with habitual tonsillitis. This suggests that some immunoregulatory dysfunction
      exists in the secretory immune system of mucosa-associated lymphoid tissues in
      patients with IgA nephropathy.

PMID- 8285043
TI  - Role of serum antibodies to streptococci in patients with IgA nephropathy.
AB  - Serum antibodies to whole cells of streptococci and serum immune complexes were
      investigated in patients with IgA nephropathy accompanied by tonsillitis and in
      healthy adult controls by enzyme-linked immunosorbent assay (ELISA). Serum IgA
      levels to Streptococcus salivarius, S. sanguis I and S. pneumoniae were higher in
      patients with IgA nephropathy than in healthy controls. The levels of IgG to S.
      pyogenes T12, S. gordonii and S. sanguis II in patients with IgA nephropathy were
      also higher than in healthy controls. Serum immune complexes of IgG and IgA were
      higher in patients with IgA nephropathy than in healthy controls. Serum levels of
      IgA to some strains of streptococci tended to correlate with the level of IgA
      immune complex in both patients and healthy controls. These results suggest that
      antibodies to some strains of streptococci play a role in the pathogenesis of IgA
      nephropathy.

PMID- 8285044
TI  - Recovery of head postural control following unilateral vestibular neurectomy in
      the cat. Neck muscle activity and neuronal correlates in Deiters' nuclei.
AB  - Recovery of head postural control after unilateral vestibular neurectomy was
      investigated in the alert cat by chronically recording the spontaneous neck
      muscle EMG activity from splenius capitis on both sides and the vestibulocollic
      reflexes evoked during roll and pitch tilts. Neuronal correlates occurring within
      the lateral (Deiters) vestibular nuclei (LVN) were also recorded during the time
      course of recovery. During the acute phase (1-2 weeks), the cats exhibited strong
      imbalance in spontaneous neck muscle activity, characterized by increased
      muscular tone in the ipsilateral splenius capitis muscle and hypoactivity in the
      contralateral one. At the same time, the mean resting activity of Deiters'
      neurons strongly decreased on the deafferented side, while a slight but
      significant decrease was observed on the intact side. Vestibulocollic reflexes
      were totally lacking during the acute phase, whatever the direction and the
      amplitude of tilt. Recovery developed in the following weeks, leading to complete
      rebalance of spontaneous EMG activity as well as near to normal static
      vestibulocollic reflexes 5 weeks after the lesion. However, compensation remained
      sub-normal during roll tilts while overcompensation was found during pitch tilts,
      suggesting that the intact labyrinth would play a leader role in the recovery
      process but that bilateral cooperation of the two labyrinths is required for
      proper head postural control. Five weeks are also needed for a partial
      rebalancing of resting activity between both LVN. These results indicate that
      changes in neck muscle activity observed in the acute cats and that recovery
      found in the compensated animals could result from modifications in neural
      networks controlling neck musculature, such as the LVN.

PMID- 8285046
TI  - [Development of pentylenetetrazol kindling model].
AB  - An ideal animal model of chemical kindling mimicking human epilepsy was developed
      in 28 day-old rats. Rats were given pentylenetetrazol (PTZ) 30 mg/kg, ip, once
      per day for 28 consecutive days; after stopping treatment for one week, the rats
      were retreated using the same dose of PTZ until reaching the kindled criterion.
      The kindled rate was 74%. The behavioral seizure and EEG discharges were
      synchronized. All kindled rats still kept their high seizure state after the
      experiments.

PMID- 8285045
TI  - [Antimutagenic activity and metabolic transformation of ranunculin by rat liver
      microsomes].
AB  - Ranunculin (RAN) was shown to be an antimutagenic agent selectively against
      mitomycin C (MMC) or methyl methane sulfanate (MMS) treated Salmonella
      typhimminum TA100/TA102. It decreased the formation of micronucleus of MMC
      induced polychromatic erythrocytes (PEC) from 46 +/- 9.2% to 20 +/- 6% in mice.
      The inhibition of RAN on the incorporation of 3H-TdR into DNA disappeared after
      incubation with rat liver microsomes and cytoplasm since RAN was found to be
      metabolized by rat liver microsomes in vitro, resulting in a new absorbance peak
      at 258 nm, determined by RP-HPLC. The data show that RAN may have both
      antimutagen and antitumor activity, but the latter action may disappear by
      metabolic transformation.

PMID- 8285047
TI  - [Effects of Phytolacca acinosa polysaccharides II on lymphocyte proliferation and
      colony stimulating factor production from mice splenocytes in vitro].
AB  - Phytolacca acinosa polysaccharides II (PAP-II), a kind of polysaccharides
      isolated from Phytolacca acinosa Roxb with MW 40 kDa, on lymphocyte proliferation
      and colony stimulating factor (CSF) production from splenocytes in vitro, was
      studied. The radioactivities of [3H] TdR uptake by lymphocyte and bone marrow
      cells were used to determine the ability of lymphocyte proliferation and CSF
      production respectively. PAP-II was found to significantly augment splenocyte
      proliferation in a dose-dependent fashion, and significantly enhance Con A (1,
      2.8 micrograms.ml-1) and LPS (3, 10, 30 micrograms.ml-1) induced lymphocyte
      proliferation at concentration of 31-125 micrograms.ml-1. As the concentration of
      PAP-II increased, significant suppression of Con A-induced lymphocyte
      proliferation was observed. Induction of CSF by PAP-II from splenocyte was
      confirmed at the present study. The optimal dosage was 100 micrograms.ml-1 and
      the optimal effect occurred on day 5. These results suggest that PAP-II can
      augment immunological function and enhance hematopoiesis.

PMID- 8285048
TI  - [Comparison between the effects of (-)- and (+)-gossypol on protein kinase C and
      protein kinase A].
AB  - Protein kinase C(PKC) and protein kinase A(PKA) purified from rat liver were
      incubated with (-)- and (+)-gossypol. The activity of PKC was significantly
      inhibited in a concentration-dependent manner by both (-)-gossypol and (+)
      gossypol. (-)-gossypol was found to inhibit type I PKA, whereas the inhibitory
      action of (+)-gossypol for type I PKA was less potent. Both (-)-gossypol and (+)
      gossypol showed inhibition for type II PKA only at high concentration. These
      results suggest that administration of gossypol might impair cellular signal
      transduction.

PMID- 8285049
TI  - Effects of dauricine and tetrandrine on [3H] WEB 2086 specific binding to bovine
      anterior cerebral arterial smooth muscle cells in vitro.
AB  - By using [3H] WEB 2086, a PAF antagonist, specific binding sites of PAF on bovine
      anterior cerebral arterial smooth muscle cells was identified. Two populations of
      binding sites with different dissociation constants on the cells were found. The
      Kd-1 = 22.8 +/- 5.0 nmol.L-1, Kd-2 = 186 +/- 20.5 nmol.L-1 at 25 C. The total
      number of binding sites were Bmax-1 = 2.1 +/- 0.3 pmol/10(6) cells and Bmax-2 =
      12.1 +/- 1.5 pmol/10(6) cells. Dauricine and tetrandrine, two active compounds
      with similar chemical structure extracted from traditional Chinese herbs, were
      found to inhibit [3H] WEB 2086 specific binding significantly in culture cells.

PMID- 8285050
TI  - [Effects of 3,6-dimethylamino-dibenzopyriodonium formiate on action potential and
      slow inward calcium current in isolated guinea pig ventricular myocytes].
AB  - The effects of 3,6-dimethylamino-dibenzopyriodonium formiate (IHC-64) on action
      potential and slow inward calcium current (I(si)) were investigated in isolated
      guinea pig ventricular myocytes using whole cell voltage clamp recording. IHC-64
      (20 and 200 mumol/L) was shown to markedly decrease APD20 and APD90. However, in
      the presence of nisoldipine, no obvious effects of IHC-64 on APD20 could be
      detected. Under voltage clamp conditions, IHC-64 (20 and 200 mumol/L) caused a
      significant decrease in I(si). The results indicate that IHC-64 can block the
      calcium channels in isolated guinea pig ventricular myocytes.

PMID- 8285051
TI  - [Synthesis of porcine brain natriuretic peptide (BNP-26) and an analog].
AB  - The porcine brain natriuretic peptide (BNP-26) and its analog, (Mpr4,D-Ala6,13)
      BNP(4-24)-NH2, were synthesized by solid phase method employing the Boc strategy.
      After HF cleavage to remove the protected groups, the crude linear peptide was
      air-oxidized under alkaline conditions to form the disulfide bridge. The
      synthetic peptides, purified by gel filtration and HPLC, were proved to have
      pharmacological spectra very similar to that of natural BNP such as
      natriuretic/diuretic, hypotensive and vaso-relaxant activities.

PMID- 8285052
TI  - [Studies on the indole alkaloids of Winchia calophylla A. DC].
AB  - Winchia calophylla A. DC. (Apocynaceac) is one traditional medicine of the Dai
      Nationality in Xishuangbanna, Yunnan Province, for the treatment of trachitis.
      Four indole alkaloids have been isolated from the stem bark and the leaves of
      this plant by aluminum oxide and silica gel chromatography. Three of them were
      identified as echitamine chloide (I), echitamidine (II) and Nb-demethyl
      echitamine (III) by comparison with literature. One of them are new, with
      structures elucidated as 22-O-acetyl-Nb-demethyl-echitamine (IV) by chemical and
      spectroscopic methods.

PMID- 8285053
TI  - [Studies on the chemical constituents of Fritillaria taipaiensis L].
AB  - A new C-nor-D-homo-steroidal alkaloid named taipaienine, together with five known
      alkaloids namely chuanbeinone, imperialine, verticinone, perimissine and
      isoverticine were isolated from the bulbs of Fritillaria taipaiensis L. var.
      ningxiaensis Y. et W.. The unusual structure of taipaienine was a first sample
      with a hydroxyl group substituted at C-25 of (22)R-trans quinolizidine moiety
      with orientation of nitrogen lone pair. Their structures were determined by
      various spectral analyses.

PMID- 8285054
TI  - [Swertiapunimarin from Swertia punicea Hemsl].
AB  - A new secoiridoid glycoside, swertiapunimarin (I), was isolated from the whole
      plant of Swertia punicea Hemsl. The structure was elucidated as 6'-O-beta-D
      glucopyranosylsweroside on the basis of chemical and spectroscopic analysis. The
      other seven known compounds were identified as sweroside (II), swertiamarin
      (III), oleanolic acid (IV), daucosterol (V), beta-sitosterol (VI), 2,3-dihydroxy
      1,4-benzodicarboxylic acid (VII) and methylswertianin (VIII).

PMID- 8285055
TI  - [Studies on two new furostanol glycosides from Allium macrostemon Bunge].
AB  - Further studies on the active constituents in the bulbs of Allium macrostemon
      Bunge led to the isolation and structural determination of two new furostanol
      saponin macrostemonoside E and F. On the basis of chemical evidences and spectral
      analysis (UV, IR, 1H-NMR, 13C-NMR and FAB-MS), the structure of macrostemonoside
      E(I) was elucidated as (25R)-26-O-beta-D-glucopyranosyl-5 alpha-furost-20(22)-ene
      3 beta,26-diol-3-O- beta-D-glucopyranosyl (1-->2) [beta-D-glucopyranosyl (1-->3)]
      beta-D-glucopyranosyl (1-->4)-beta-D-galactopyranoside; macrostemonoside F(II)
      was established to be (25R)-26-O-beta-D-glucopyranosyl-5 beta-furost-20(22)-ene-3
      beta,26-diol-3-O- beta-D-glucopyranosyl (1-->2)-beta-D-galactoside. Preliminary
      pharmacological tests showed that both macrostemonoside E and F could strongly
      inhibit ADP-induced human platelet aggregation in vitro. The IC50 of the former
      was 0.417 mM and that of the latter was 0.020 mM.

PMID- 8285056
TI  - [Determination of berberine in biological specimen by high performance TLC and
      fluoro-densitometric method].
AB  - In this paper, a simple and specific high performance TLC and fluoro
      densitometric method for separating and determining berberine in biological
      specimen was developed. Two hundred microliters of plasma or tissue homogenate
      mixed with 20 microliters of sodium lauryl sulfate (18%) and quinidine (300 ng,
      as internal standard) were extracted with 1 ml of chloroform. The developing
      solvent consisted of ethyl acetate-methyl acetate-methanol-water
      (5.4:4.6:1.2:1.0). The determination was carried out with a Shimadzu TLC-Scanner
      CS-910. Berberine spots were measured using an excitation wavelength of 350 nm
      and an emission wavelength of 550 nm, while using 350 nm and 450 nm for quinidine
      spots as the excitation and emission wavelength respectively. The average
      recoveries were 100.3% from plasma and 103.8% from tissue homogenate. The
      berberine levels in plasma and in tissues were compared in normal mice after oral
      administration of berberine (100 mg/kg) or the powder of Coptis chinensis (2
      g/kg) containing the same amount of berberine. Simultaneously, the hypoglycemic
      effect of berberine and that of the powder of Coptis chinensis were measured in
      these mice. Results indicate that the concentrations of berberine in plasma and
      tissues given the powder of Coptis chinensis orally were higher than those given
      berberine and that the hypoglycemic effect of the powder was also stronger than
      that of berberine. Evidently, the changes of the blood glucose level and the
      level of berberine in plasma showed an opposite relationship.

PMID- 8285057
TI  - [Determination of major volatile components in suhexiang wan (storax pill) using
      analytical supercritical fluid extraction (SFE)].
AB  - A new method based on the off-line coupling of analytical SFE and GC has been
      developed for qualitative and quantitative analysis of major volatile components
      in Suhexiang Wan, a Chinese patent medicine. The factors affecting extraction
      efficiency were examined to seek the optimal operating parameters. Quantitative
      recovery (90%) was achieved with 20 ml CO2 in ca 1 h using a self-designed
      analytical SFE system. Compared with the conventional methods, the SFE as an
      alternative technique for sample preparation will be most useful in the quality
      control of Chinese patent medicine.

PMID- 8285058
TI  - [Separation and quantitative determination of seven aqueous depsides in Salvia
      miltiorrhiza by HPTLC scanning].
AB  - A new analytical method for the separation and determination of seven aqueous
      depsides in salvia miltiorrhiza by HPTLC has been developed. The seven depsides
      are protocatechualdehyde, caffeic acid, methyl rosmarinate, rosmarinic acid,
      salvianolic acid A, B and C. Using chloroform-ethyl acetate-benzene-formic
      acid(2.4:2:1:0.6) as developing solvent A, protocatechualdehyde was separated;
      using chloroform-ethyl acetate-benzene-formic acid-methanol (1.5:2:1:1:0.1) as
      developing solvent B, the other six constituents were well separated. The aqueous
      depsides were detected at the wave lengths of lambda S = 300 nm and lambda R =
      240. This method is simple, rapid, sensitive and accurate. The contents of seven
      depsides in several Salvia species were determined.

PMID- 8285059
TI  - [Synthesis and platelet aggregation inhibitory activity of 6-substituted
      dihydropyridazinones].
AB  - In order to develop more potent and less toxic antithrombotic agents, ten 6-(4
      substituted piperazinyl acetyl aminophenyl)-4,5-dihydro-3(2H)-pyridazinones were
      synthesized. The title compounds were tested in vitro for platelet aggregation
      inhibitory activity with ADP-induced rat platelets and PAF-induced rabbit
      platelets. Preliminary tests showed that all of the pyridazinones could inhibit
      ADP-induced rat platelet aggregation. I7, I8, I9 were more potent than the
      control compound CI 930. I9 was the most potent compound with IC50 of 0.99
      mumol/L. Pertaining to PAF-induced rabbit platelet aggregation, I9 was the most
      potent inhibitor with IC50 of 3.7 mumol/L.

PMID- 8285060
TI  - [Studies on chemotherapeutic agents against Schistosomiasis japonica: synthesis
      of benzimidazole derivatives].
AB  - A series of 3-(1H-benzimidazole-2)-2-propenoic acid derivatives were prepared and
      tested for schistosomicidal activity. The acid was proved to be a cis-isomer.
      Preliminary pharmacological tests showed that these compounds were in effective.

PMID- 8285061
TI  - [Preparation and structural elucidation of insularine-N-oxides].
AB  - Oxidation of insularine (I) with m-chloroperbenzoic acid yielded four insularine
      N-oxides. Two of them are identical in every respect with our insularine-2 beta-N
      oxide (II) and insularine-2' beta-N-oxide (III), two rare examples of naturally
      occurring head-to-tail bisbenzylisoquinoline N-oxides newly isolated from Cyclea
      sutchuenensis, which confirmed the structures of the two novel natural N-oxides.
      The other two are new compounds and their structures have been established as
      insularine-2' alpha-N-oxide (IV) and insularine-2 beta,2' beta-N, N-dioxide (V),
      on the basis of spectral data (UV, IR, 1HNMR, NOEDS AND MS) analysis.

PMID- 8285062
TI  - [Protective effects of combination of chlorpromazine and verapamil on ischemia
      reperfusion induced injury in rat myocardium].
AB  - Combination of chlorpromazine (CPZ) and verapamil (Ver) was found to decrease the
      incidence of ventricular arrhythmias and ventricular fibrillation induced by
      myocardial ischemia and reperfusion, lower serum creatine phosphokinase (CPK) and
      decrease the content of malondialdehyde (MDA) in heart tissue homogenate
      especially in mitochondria; and increase the phospholipid content and the
      phospholipid/cholesterol ratio; and decrease the myocardial "cell calcium"
      content in the reperfused area. The effect of CPZ and Ver combination was better
      than either CPZ and Ver alone.

PMID- 8285063
TI  - [The effect of zinc glycyrrhizate on toxicity and anticancer activity of
      cisplatin in mice].
AB  - The preventive effects of Zn Glycyrrhizate (Gly-Zn) on lethal toxicity,
      nephrotoxicity, hemotoxicity, testicular toxicity and anticancer activity of
      cisplatin (CDDP) were investigated in mice. The toxicity of CDDP evaluated by the
      above criterion was significantly reduced by preadministration of Gly-Zn 400
      mg.kg-1.d-1 x 5 (P < 0.05 or P < 0.01). The protective effects were better than
      bismuth subnitrate (BSN) which has been studied previously (0.05 < P < 0.1). The
      metallothionein (MT) level in the liver, kidney, heart and cancer of mice treated
      with one of these compounds were determined. The results showed that the levels
      of MT induced by Gly-Zn were significantly increased in liver and kidney (P <
      0.05). It was just in conformity with the conclusion that the best protective
      effect appeared in the groups treated with preadministration of Gly-Zn. These
      results suggest that increased MT synthesis in the liver and kidney may be
      involved in the protective effect of Gly-Zn on the toxicities produced by CDDP.
      The experiments also showed that Gly-Zn did not affect the anticancer effect of
      CDDP in vitro and in vivo, while the MT level was not increased in cancer (P <
      0.05), so Gly-Zn might improve the therapeutic index of CDDP.

PMID- 8285064
TI  - [The protective action of glycyrrhiza flavonoids against carbon tetrachloride
      hepatotoxicity in mice].
AB  - The protective action of Glycyrrhiza flavonoids (GF), the major components in the
      radix of Glycyrrhiza, on carbon tetrachloride-induced hepatotoxicity was
      investigated. The carbon tetrachloride-induced increases of serum glutamic
      pyruvic transaminase and lactate dehydrogenase were significantly inhibited by GF
      dose-dependently. Carbon tetrachloride-induced necrosis in mice were ameliorated
      by GF pretreatment. Concomitantly, the carbon tetrachloride-induced elevation of
      MDA in the liver was lowered by GF. GF neither reduced the activities of the two
      enzymes in normal mouse sera nor directly inhibited the activities of the two
      enzymes in the serum. These findings suggest that the anti-lipid peroxidation
      effect of GF was contributed to its protective action against carbon
      tetrachloride-induced hepatotoxicity.

PMID- 8285065
TI  - [Effects of Ganoderma polysaccharides on the activity of DNA polymerase alpha of
      splenocytes and immune function in aged mice].
AB  - The activity of DNA polymerase alpha in splenocytes of 24-month-old mice was
      about 35.6% lower than that of 3-month-old mice. Aged mice were intraperitoneally
      administered Ganoderma polysaccharides (GL-B) once a day for 4 days and then the
      activity of the enzyme was assessed. The results showed that GL-B at doses of 25
      and 50 mg/kg-1 enhanced the activity of the enzyme in aged mouse splenocytes by
      44.0 and 58.8% respectively. In addition, the mixed lymphocyte response to
      alloantigen, automatic proliferation and IL-2 production of splenocytes in aged
      mice declined as compared with that in young adult mice. GL-B (50, 100, 200
      micrograms.ml-1) was found to restore those parameters to the levels of that of
      young mice in vitro.

PMID- 8285066
TI  - [Structural congeners of guanfu base A and their antiarrhythmic activity].
AB  - Guanfu base A (GFA) is an alkaloid isolated from the root of Aconitum coreanum
      and is effective in several experimental arrhythmia models. GFA can effectively
      antagonize aconitine-induced arrhythmia, significantly reduce CaCl2-induced
      incidence of ventricular fibrillation in rats and markedly raise the ventricular
      fibrillation threshold to electrical stimulation in rabbits and cats. It would be
      valuable in clinic to treat ventricular fibrillation. Thus, we chose GFA as lead
      compound for chemical modification. From the view point of stereochemistry, GFA
      is a rigid structure and can be considered as composed of two layers. The first
      layer is a hydrogenated phenanthrene ring; the second is the alkylamino chain
      containing hydroxy and acetoxy groups [formula: see text]. It was speculated that
      the skeleton of such chain might play as pharmacophore contributing to the
      biological activity. In order to reduce the size of the molecule and simplify the
      chemical structure of GFA, the hydrogenated phenanthrene was removed and an aryl
      residue commonly occurred in the structure of antiarrhythmic agents was
      introduced. Thus, fourteen derivatives of phenylpropanediolamine were designed
      and synthesized. There is a hydrogenated indolizine ring in the structure of GFA
      and a indolizine ring in the structure of class III antiarrhythmic agent-
      butoprizine. By combing the structural feature of GFA with that of butoprizine,
      nine indolizine derivatives were also designed and synthesized. Screening test of
      23 compounds indicated that phenylpropanediolamine derivatives--I1, I2, I3, I7,
      I8, I14, and indolizine derivatives--II2 markedly antagonized chloroform-induced
      arrhythmias in rats. Among them I2, I3, I7 and I8, appeared to be more potent
      than GFA.

PMID- 8285067
TI  - [Synthesis of pyronaridine related compounds and comparison of antimalarial
      activities].
AB  - The paper reports the synthesis of pyronaridine (I) related compounds II-V for
      exploring whether the antimalarial activity of pyronaridine is by virtue of a
      nitrogen atom at position 1 in the ring and a pair of pyrrolidinyl Mannich base
      side chains in its structure. The condensation of 2-methoxy-6,9-dichloroacridine
      or 4,7-dichloro-1,5-naphthyridine with 4-hydroxy-3,5-bis-(pyrrolidinyl-1'-methyl)
      aniline yielded the related compound II, 1-deazapyronaridine, or V, 5
      azabispyroquine, respectively. 2-Methoxy-7,10-dichlorobenzo (b) 1,5-naphthyridine
      or 4,7-dichloro-1,5-naphthyridine was condensed with 4-diethylamino-1
      methylbutylamine to obtain the related compound III, azacrin, or IV, 5
      azachloroquine, respectively. The results of in vivo tests against Plasmodium
      berghei chloroquine-resistant ANKA strain, drug-sensitive P. berghei N line and
      drug-resistant P. yoelii nigeriensis line showed that all the related compounds
      II-V were less effective than pyronaridine (I). It suggests that the nitrogen
      atom at position 1 and pyrrolidinyl Mannich base side chains on the structure of
      pyronaridine play an important and indispensable role for antimalarial activity
      of pyronaridine. The pyrrolidinyl Mannich bases impart increased activity to the
      corresponding compounds.

PMID- 8285068
TI  - [Two novel bisbenzylisoquinoline alkaloids from Cyclea sutchuenensis Gagnep].
AB  - In addition to the known cycleanine (I) and d-isochondodendrine (II), two novel
      bisbenzylisoquinoline alkaloids named isocycleanine (III) and sutchuenensine (IV)
      have been isolated from the roots of Cyclea sutchuenensis Gagnep grown wild in
      Sichuan province, China. III was established as the epimer of I and IV, as a new
      type of head-to-tail bisbenzylisoquinoline alkaloid with two diarylether bridges
      in between C-8 to C-12' and C-12 to C-7' on the basis of physical constants and
      spectral data (UV, IR, EIMS, 1HNMR and NOEDS).

PMID- 8285069
TI  - [Study on cisplatin albumin microspheres for neck external artery embolization].
AB  - In this paper the technique of emulsion chemical-crosslinking was used to prepare
      cisplatin albumin microsphere for jaw squamous cancer by neck external artery
      embolization. It was yellow powder with yield 80 +/- 5%, mean size 56.3 microns,
      cisplatin concentration 14.02-14.20%, loading rate 97.08-97.95%. The release
      characteristics in vitro, sterilization, stability and recipe of disperse solvent
      of cisplatin albumin microsphere were investigated. Animal test showed that
      cisplatin albumin microsphere may plug the branches of neck external artery well
      and remain in local tissue.

PMID- 8285070
TI  - [The bioavailability of transdermal therapeutic system of timolol].
AB  - A matrix-type transdermal therapeutic system of timolol (TTS-timolol) was well
      prepared. The patch consisted of backing membrane layer, timolol reservoir layer,
      pressure sensitive adhesive layer and protective layer. A sensitive and reliable
      HPLC-UV method for the determination of plasma level of timolol in healthy
      volunteers was developed. Effective therapeutic plasma level of timolol (4 ng/ml)
      was attained 4 h after application of the timolol patches and was maintained
      within 32 h while the patch was removed at 24 h. The pharmacokinetic behavior of
      this transdermal therapeutic system (TTS)-timolol in human showed zero order
      absorption and well fitted to a one compartment model. The pharmacokinetic
      parameters are: Tmax = 18.8 h; Cmax = 11.2 ng/ml; AUC = 265.7 ng/ml.h; Vss =
      120.0 L; K = 0.084 h-1. In comparison with the results of oral administration of
      timolol tablets, TTS-timolol possesses some advantages: stable plasma level, long
      effective time and convenient administration.

PMID- 8285071
TI  - Effects of kappa-selenocarrageenan on lymphocyte proliferation and antibody
      productive cells in immunosuppressed mice.

PMID- 8285072
TI  - [Studies on uranium mobilization agents VI: synthesis of 2,3-dihydroxy-4
      carbomethoxybenzyl aminocarboxylic acid amides chelating agents].
AB  - In searching for new chelation therapy drugs against uranium intoxication, a
      series of N-carboxymethyl-N-(substituted carbamoylmethyl)-2,3-dihydroxy-4
      carbomethoxybenzylamine was synthesized starting with o-vanillin. The effect on
      detoxication of UO2(NO3)2, CuSO4 and NiCl2 in mice was tested. Some of them (IVa,
      IVd, IVf and IVg) were shown to be good antidotes for acute uranium intoxication,
      but all were less effective for Cu2+ and Ni2+.

PMID- 8285073
TI  - [Isolation and identification of gancaonin P-3'-methylether from the leaves of
      Glycyrrhiza uralensis Fisch].
AB  - Two flavonoids were isolated from the leaves of Glycyrrhiza uralensis Fisch
      (Licorice, Leguminosae). On the basis of physico-chemical properties and
      spectroscopy (UV, 1HNMR and MS), a new compound was elucidated as 3,5,7,4'
      tetrahydroxy-3'-methoxy-6-isoprenyl flavone (gancaonin P-3'-methylether) and
      another known compound was identified as 8-C-prenyleriodictyol.

PMID- 8285074
TI  - [Photodegradation assay method of nifedipine and its application to studies on
      percutaneous absorption].
AB  - A new method of analysis for low concentrations nifedipine was developed
      according to the principle of a photodegradation analytical method that has been
      reported by the authors previously, and was used to study percutaneous
      absorption. The absorbance of sample solution was measured before and after light
      irradiation at 237 nm for 2 h. In this method, calibration graph was linear in
      the range of 1-20 micrograms/ml for delta A237. The average recovery for
      nifedipine was 98.80%. No interference from propylene glycol, azone, m
      nifedipine, nitrendipine, verapamil and propranolol was observed. It is shown
      that azone can promote markedly percutaneous absorption of nifedipine.

PMID- 8285075
TI  - [Determination of acyclovir in human plasma by RP-HPLC].
AB  - A RP-HPLC method was developed for the determination of acyclovir (ACV) in human
      plasma. ACV was extracted from plasma using ODS, obtained from Sep-Pak C18
      cartridge (Waters associates) and reinstalled in a self-made glass tube suitable
      for extraction of solutes from small volume plasma samples. After extraction, and
      rinsing the ODS extract with water to remove hydrophilic impurities, ACV was
      recovered with methanol and chromatographed on YWG C18H37 column, and detected at
      254 nm. The mobile phase was 5.0% (v/v) methanol/water. The average recovery of
      ACV was 73.5%; the minimum detection concentration of ACV in plasma was 20 ng/ml
      with a plasma volume of 0.2 ml and S/N value of 2. A good linear relationship
      between the peak area ratios and ACV concentrations was found at the ACV
      concentrations ranging from 0.2 to 1.0 microgram/ml, CACV = 0.840 AACV/Ais +
      0.002, r = 0.9969.

PMID- 8285076
TI  - [The degradation mechanism of penequine hydrochloride in aqueous solutions].
AB  - Penequine hydrochloride (I) is a new potent anticholinergic drug, the degradation
      mechanism of I in aqueous solutions is reported in this paper. I is an ethereal
      compound, stable in neutral and alkaline solutions, but it decomposes in strong
      acidic solutions. Its main degradation products have been separated and
      identified by means of TLC, MS, GC/MS and GC/FTIR. With reference to the general
      degradation rule of ethereal compound and the structure of the degradation
      products, we deduced that the ether linkage of I splits in acidic solutions by
      the catalysis of hydrogen ion, producing 3-quinuclidinol (DP1) and 1-phenyl-1
      cyclopentyl glycol. The latter turns into 1-phenyl-1-cyclopentyl acetaldehyde
      through dehydration and rearrangement. In addition, small amounts of other
      degradation compounds, e. g. benzaldehyde, acetophenone, phenylcyciopentyl
      ketone, etc. have also been found, but the mechanism remains to be further
      studied.

PMID- 8285077
TI  - On the time course and accuracy of spatial localization: basic data and a two
      process model.
AB  - This article addresses the question how fast and accurate the location of a
      single stimulus can be perceived. In Experiment 1, we measured localization
      performance in a task which required subjects to perceive and report the location
      of a single target stimulus ('*' sign) presented in one square of an imaginary 25
      x 19 grid. Two factors were varied: stimulus duration and stimulus eccentricity.
      Stimulus duration was manipulated by employing a backward masking stimulus. Ten
      intervals (stimulus onset asynchronies) separated target and masking stimulus:
      25, 50, 75, 100, 125, 150, 200, 250, 300, and 350 ms. Stimulus eccentricity was
      manipulated by presenting the target stimulus at five different distances from
      the fixation point. The observer localized the target stimulus by moving the
      cursor from the middle of the grid (the initial fixation point) to the perceived
      target location by pressing the 'arrow' keys on the keyboard. Localization
      performance showed to be typically related to stimulus duration. That is, two
      components could be distinguished: The first component represented an initial
      steep rise in localization performance during the first 50 ms of stimulus
      duration; the second component represented a gradual rise in localization
      performance after 50 ms, reaching maximal performance at about 300 ms. We
      interpreted these two localization performance functions as reflecting the
      operation of two systems, namely the attentional system for the initial strong
      increase and the eye movement system for the subsequent gradual increase. In
      Experiment 2, we measured saccadic eye response latencies to clarify the role of
      eye movements in localization performance. It was found that in 98.4% of all
      trials saccades were executed, and, moreover, that saccadic eye response latency
      decreased with increasing stimulus duration. In Experiment 3, we compared
      localization performance in the absence and presence of eye movements and
      demonstrated that localization performance for stimulus durations up to 50 ms was
      independent of eye movements. Overall, the present findings were interpreted as
      evidence in support of a two-process model of localization performance in which a
      shift of attention is followed by a rapid eye movement toward the target
      location. In line with a continuous flow conception of visual information
      processing, our model assumes that location information takes time to develop in
      the visual system; hence, an observer's localization response may be based on
      qualitatively different processes operating on qualitatively different kinds of
      information. In case of short duration stimuli, information conveyed by transient
      cells is used by the attentional system to shift attention toward the target
      location; this results in course location information being available.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8285078
TI  - Mental accounting and the process of multiattribute choice.
AB  - Tversky and Kahneman (1981) discussed how multiattribute choices may be framed in
      terms of alternative psychological accounts established for specific problems.
      They identified three levels of account: minimal, topical and comprehensive. The
      role of these mental accounts is investigated in two studies of Tversky and
      Kahneman's Jacket and Calculator problem. In the first, systematic variation of
      jacket and calculator prices showed that the latter had a large effect on choice,
      and the former a small but significant effect. It is concluded that: (1) the
      effect of the calculator price supports Tversky and Kahneman's view that people
      frame simple choices in terms of specific, topical accounts; and (2) the jacket
      price effect supports the view that more comprehensive mental accounts also
      influence evaluation and choice. In the second study, think aloud evidence is
      presented which supports these conclusions and indicates that the level of
      account adopted may be contingent on characteristics of the choice problem.

PMID- 8285079
TI  - Effects of extended practice in a one-finger keypressing task.
AB  - This paper addresses skilled operations underlying the initiation and execution
      of rapid movement sequences in a task consisting of three sequential keypresses
      made with one finger. It sought to provide evidence for the notion that, as a
      result of practice, processes required to produce a keypressing sequence become
      concurrent. The results of the experiment show, first, that unpacking of the
      third keypress in a three-keypress sequence, which is assumed to occur normally
      after execution of the second keypress, is shifted in time during practice so as
      to occur during or before actual depression of the second key. Second, no
      evidence was found that selection of a stimulus-dependent key occurring later in
      the sequence could be performed during execution of earlier, stimulus-independent
      keypresses. Third, the pattern of dual-task interference suggested that attention
      is required for preparing as well as for executing movement sequences. Dual-task
      interference hardly reduced with practice which was interpreted as evidence for
      the notion that reduction of attentional demands of keypressing with practice is
      used only for increasing the amount of concurrent unpacking. In conclusion, the
      present experiment suggests that a major reason that movement sequences are
      executed faster with practice is that the reduction of attentional demands of
      individual subprocesses is utilized to increase the amount of concurrent
      processing.

PMID- 8285080
TI  - Practice management research.

PMID- 8285081
TI  - Identifying gestational diabetes mellitus: research needs.

PMID- 8285082
TI  - Methodological issues in conducting a community-based clinical drug trial.
AB  - OBJECTIVE: This paper explores the advantages and disadvantages of implementing a
      clinical drug trial in a closed community. METHODS: In the study we conducted a
      randomized, double-blind, placebo-controlled clinical trial to evaluate the
      effects of an antacid containing aluminum hydroxide on serum lipoproteins in
      hypercholesterolemic adults. RESULTS: The results of the trial, which was
      conducted on two Israeli kibbutzim (rural cooperative communities), have been
      published previously. CONCLUSIONS: The kibbutz presents a unique setting for the
      conduct of a clinical trial. There were opportunities to uphold inclusion and
      exclusion criteria carefully, to obtain informed consent, to enhance dietary and
      drug adherence, to ensure the quality of data collection, to maintain the
      interest of the participants in the study, and to monitor closely adverse effects
      and patient safety. This report describes the unique circumstances under which
      the trial was conducted and the role of the clinician as a clinical investigator
      and discusses their implications for the internal validity and generalizability
      of the trial.

PMID- 8285083
TI  - Family medicine in Minnesota: office costs and productivity.
AB  - Clinics representing more than half of Minnesota's family physicians participated
      in a statewide study on the practice of family medicine conducted by the
      Minnesota Academy of Family Physicians. The survey was designed to provide
      direction for individual physicians, administrators, and the Minnesota Academy of
      Family Physicians as an organization. The survey identified some concerns
      regarding access to care. In the central portion of the state, 71% of the full
      time equivalent family physicians were in practices with Medicaid patient
      restrictions. In the most sparsely populated towns, 35% of the reporting family
      physicians who provided obstetrical care three years ago discontinued that
      service due to the cost or availability of professional liability coverage.
      Statewide in 1989, 57% of the family physician positions recruited for by the
      practices studies were unfilled at year's end, with 82% unfilled in the most
      sparsely populated areas.

PMID- 8285084
TI  - Assessing bad debt in New Hampshire and Vermont office-based practices.
AB  - OBJECTIVE: Bad debt is one measure of the cost of medical indigence on health
      care institutions. This two-part study identifies a methodology for and presents
      findings from measuring bad debt in a collection of office-based practices.
      METHODS: In Part I of the study, data were gathered on site from 26 practices in
      Sullivan County, New Hampshire, after first conducting a survey of bad debt
      losses at these offices. Survey findings were compared to on-site findings and it
      was determined that only the practices with computerized record-keeping systems
      were able to supply accurate data by survey alone. In Part II, 71 randomly chosen
      computerized practices in New Hampshire and Vermont (identified in a screen of
      275 practices) were surveyed on bad debt. RESULTS: The practices from Part II
      wrote off an average of $23,115 per physician in 1990 from bad debt in a region
      in which primary care physician income averages approximately $70,000.
      CONCLUSIONS: The author calculates that bad debt losses are greater than either
      Medicare or Medicaid losses. Uninsured patients account for 21.6% of office
      visits but 45% of practice write-offs. Bad debt accounts for a 16% loss from
      total earnings from regular office visits. Office-based practices in this study
      are shouldering a significant portion of the cost of care of their uninsured and
      underinsured patients.

PMID- 8285085
TI  - Clinical decision-making following abnormal Papanicolaou smear reports.
AB  - OBJECTIVE: Interpretation of abnormal Papanicolaou smear reports and the
      subsequent management of the patient frequently present significant decision
      making problems for clinicians. The purpose of this study was to evaluate family
      physician clinical decision-making strategies for abnormal cervical cytology
      reports using simulation techniques. METHODS: One hundred fifteen practicing
      family physicians evaluated two simulations of women with abnormal cervical
      cytology, the first with inflammatory cytology and the second with a high-grade
      squamous intraepithelial lesion. RESULTS: Most physicians (66%) selected an
      etiology evaluation and specific treatment approach to an inflammatory report,
      while 26% of respondents chose empiric treatment. For the high-grade squamous
      intraepithelial lesion simulation, 88% of physicians chose the appropriate
      management response of colposcopic evaluation. CONCLUSIONS: Practice experience,
      level of involvement, clinician gender, and type of cervical cytology
      classification influenced family physician clinical decision-making. The majority
      of responses to an inflammatory or high-grade squamous intraepithelial lesion
      report was appropriate based on current scientific data.

PMID- 8285086
TI  - Characteristics of colon cancer at time of presentation.
AB  - OBJECTIVE: To evaluate the relationships between demographic and clinical
      characteristics and the stage and site of colon cancer at the time of
      presentation. METHODS: New cases of colon cancer identified through a tumor
      registry at a teaching hospital during 1989 were reviewed retrospectively. Of the
      110 cases, 53% of the subjects were female, 95% were white, and 63% were more
      than 70 years of age. RESULTS: Early stages of colon cancer (Dukes A [11%] or B
      [41%]) occurred in 52%, and late stages (Dukes C [26%] or D [22%]) in 48%. Most
      patients (88%) presented with symptoms; 12% of the cases were detected in
      asymptomatic patients. Of the 13 asymptomatic patients, 7 were identified by
      positive occult blood in the stool, 5 by colonoscopy, and 1 during a
      hysterectomy. The stage of colon cancer was more likely to be early in
      asymptomatic patients (85% Dukes A or B) compared to those with symptoms (47%
      Dukes A or B) (p < 0.02). Sixty-two percent (62%) of the cecum/ascending colon
      cancer were early compared to 46% of the cancers in other locations (p = 0.11).
      Seventy-seven percent (77%) of the asymptomatic cancers were located in the
      cecum/ascending colon compared to 33% of the symptomatic patients (p < 0.02). Age
      and gender were not associated with site or stage of colon cancer. CONCLUSION:
      The majority of patients with colon cancer are diagnosed when symptomatic. When
      colon cancer is diagnosed while still asymptomatic, it is more likely to be at an
      early stage. The most common screening procedure leading to diagnosis in
      asymptomatic patients is the identification of fecal occult blood. Colon cancer
      is more likely to be located in the cecum/ascending colon when diagnosed at an
      asymptomatic stage.

PMID- 8285087
TI  - Chlamydia trachomatis screening in a family planning clinic.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of chlamydia
      in women attending a family planning clinic and to explore the feasibility of
      making chlamydia screening part of the routine procedure for all women. This
      study also investigated clinical and demographic parameters that may be
      associated with chlamydial infections. METHODS: Subjects were 239 female patients
      who attended the Planned Parenthood Clinic in Wichita, Kansas, during July 1990.
      Subjects included all patients receiving pelvic examinations regardless of
      indication. Each subject was screened for C. trachomatis using Testpack Chlamydia
      (Abbott Labs). RESULTS: Of the 239 women screened, 11 (4.6%) had positive
      Testpack Chlamydia tests. Young age (< 24 years), self-reported bleeding, and
      inflammation found on Papanicolaou exams were positively associated with
      chlamydial infection. CONCLUSION: These parameters provide additional information
      for the clinician deciding who should be screened for chlamydia infections.

PMID- 8285088
TI  - Sleep, psychological distress, and somatic symptoms in perimenopausal women.
AB  - OBJECTIVE: Self-report and somnographic data from 135 volunteer, disease-free,
      women (37-59 years) were used to determine the prevalence of perceived poor sleep
      and to compare women with and without "poor" sleep on menopausal status,
      somnographic sleep, psychological distress, and somatic symptom cluster
      frequencies. METHODS: Data from identical measures done on two groups of
      perimenopausal-age women, one recruited for menopausal age and the other for same
      age but sleep problems plus controls, were tested using a two-way analysis of
      variance for the main effects of recruitment group and the presence or absence of
      "poor" sleep as well as the joint effects of both. RESULTS: "Poor" sleep was
      reported by more than one-third of the women, but menopausal status and perceived
      sleep quality were not statistically related. Women with "poor" sleep took longer
      to fall asleep, spent longer in bed, and had higher scores for psychological
      distress and for four out of five somatic symptom clusters (p < or = 0.03),
      compared to women with "good" sleep. CONCLUSION: In sum, midlife women reporting
      poor sleep are likely to have trouble falling asleep and to have higher
      psychological distress and somatic symptoms, especially musculoskeletal
      discomfort and fatigue, coinciding with their perceived poor sleep.

PMID- 8285090
TI  - The structure and activity of primary care research networks.

PMID- 8285089
TI  - The effect of a rural family practice preceptorship on medical students'
      residency selection.
AB  - OBJECTIVE: We suspected our senior medical student rural family practice
      preceptorship was a positive influence on students' selection of family practice
      as a specialty. METHODS: A five-year study of 598 students' specialty choices
      before and after their preceptorship was done and compared to eventual residency
      choice. RESULTS: Of these students, 565 (94.5%) appeared to be uninfluenced by
      the preceptorship. Of the 33 students who reported a change in residency choice
      after completing the rural preceptorship, 15 (2.5%) chose a family practice
      residency. CONCLUSIONS: The rural preceptorship was found to have a positive
      influence on students' choice of family practice residency positions.

PMID- 8285091
TI  - Systematic cholesterol screening during acute care visits.
AB  - BACKGROUND: Physicians rarely offer clinical preventive services to patients
      during acute care visits, but only a minority of patients schedule health
      maintenance visits. Consequently, many eligible patients never receive
      appropriate preventive care. Successful strategies are needed to deliver
      preventive services during acute care visits. METHODS: This study tested the
      feasibility and effectiveness of a simple, physician-initiated protocol for
      management of hypercholesterolemia in one nonacademic community primary care
      (family practice) practice. Cholesterol testing was offered to all adult patients
      (aged 18 years or older) encountered by the clinician during acute care visits,
      as well as during scheduled health maintenance visits. Mailed notification of
      cholesterol risk status with a recommendation to follow a prudent (Step I) diet
      was the main intervention. Some high-risk patients additionally received formal
      dietary counseling and lipid-lowering medication as clinically warranted.
      RESULTS: A total of 1334 patients (95 percent of the eligible clinical
      population) accepted cholesterol testing, and 158 (11.8 percent) had high
      cholesterol (> or = 240 mg/dL). For the 114 patients (72.2 percent) with high
      cholesterol (mean 275.1 mg/dL) who returned for follow-up, cholesterol change 1
      year after screening was -9.2 percent (P < 0.001, compared with base line). This
      decrease could not be explained by expected temporal trends or regression to the
      mean. Assuming unchanged cholesterol values for patients not followed up,
      decrease for the entire clinical population with high cholesterol was -6.8
      percent (95 percent confidence interval -4.9 to -8.6 percent). CONCLUSIONS:
      Systematic cholesterol screening during acute care visits is a feasible and
      effective adjunct to screening during health maintenance visits in this practice.
      Because most people eventually visit a primary care physician, offering clinical
      preventive services during acute care visits might be an effective method for
      reaching the entire clinical population.

PMID- 8285092
TI  - Cost-effectiveness of cervical cytologic examination during pregnancy.
AB  - BACKGROUND: We undertook a study to determine the cost-effectiveness of
      performing routine cervical cytologic examination during pregnancy. METHODS: The
      costs generated by doing routine prenatal cervical cytologic examination were
      calculated based on chart review in a family practice setting. A consecutive
      sample of 523 patients giving birth during 1990 was used. Analysis was done on
      423 of those patients with prenatal Papanicolaou smear results recorded. Cost
      savings from detection of curable disease and utility of the test in terms of
      well-years saved were calculated from published statistics using a single-step
      Markov process to model the population at risk. RESULTS: For patients of all ages
      using a discount rate of 5 percent, the cost generated by prenatal cervical
      cytologic examination was $146,400 per well-year of life saved. Age
      stratification showed cost per well-year to range from $321,600 for patients aged
      15 to 19 years to $48,800 for those aged 35 to 39 years. CONCLUSIONS: Routine
      prenatal cervical cytologic examination is significantly less cost-effective than
      the most commonly done medical procedures. If medical funding is limited,
      elimination of this test should be considered for women with normal findings on
      cervical cytologic examinations within the previous 2 to 3 years.

PMID- 8285093
TI  - Women's responses to the mammography experience.
AB  - BACKGROUND: Accounts of mammography-related anxiety, embarrassment, and pain have
      been barriers to women contemplating a mammogram. Because it is not known how
      many women have had bad mammography experiences, we designed a study to learn
      what women actually experience when they have a mammogram. METHODS: Two hundred
      fifty-five women were interviewed immediately after having a mammogram at three
      different breast-imaging centers in the Philadelphia area. RESULTS: Significant
      racial differences were noted in this study with reports of mammography-related
      anxiety and pain. Nonwhite women and women who had less than a high-school
      education reported significantly more anxiety about having a mammogram. Sixty
      percent of all women interviewed were anxious about having a mammogram; 20
      percent of them reported being extremely anxious. White women reported pain more
      often than African-American women. Only 12 percent of the women reported that
      their physicians had explained the mammography procedure, but 61 percent of those
      women reported no anxiety versus 37 percent of women whose physicians did not
      explain the procedure. More than one-third (34 percent) of women having a first
      mammogram stated that their mammogram experience affected their future plans for
      having another. CONCLUSION: Extra physician or nurse time spent in explaining
      mammography to women could result in lower anxiety, higher levels of future
      intentions to get mammograms, and better experiences for the women themselves.

PMID- 8285094
TI  - Physician perspectives on the causes of rural hospital closure, 1980-1988.
AB  - BACKGROUND: Few studies seeking to determine the causes of rural hospital closure
      have examined the opinions of individuals intimately involved with the closed
      facilities. The purpose of this research was to examine the reasons for small
      sole community general hospital closures from the perspective of local physicians
      and to compare these reasons with the perceptions of local mayors. METHODS:
      Hospitals in this study were selected from a list provided by the American
      Hospital Association. A two-page questionnaire was sent to every physician who
      had practiced in the towns in which a sole community general hospital had closed
      between 1980 and 1988. RESULTS: Physicians reported government reimbursement
      policies as the most important reasons for hospital closure, agreeing with the
      mayors' opinions. Other reasons cited were general financial difficulties,
      competition from other hospitals, and bad board leadership. More than three
      quarters of the physicians surveyed considered the quality of care provided by
      their facilities to be average or better. CONCLUSIONS: The closure of rural
      hospitals that physicians consider of average or better quality suggests that
      many of the closed hospitals could have continued to provide valuable services to
      the residents of their communities. Efforts must be made to ensure that rural
      communities are not losing viable and useful facilities.

PMID- 8285095
TI  - Care of the organ transplant recipient.
AB  - BACKGROUND: Organ and tissue allografting is now a commonly performed procedure.
      Patients receiving allografts and immunosuppressive medication are no longer
      restricted to a few specialized centers and areas of the country. Because
      transplant recipients are leading longer and healthier lives, these patients are
      appearing in diverse medical settings where expertise in transplantation is not
      generally established. Because many generalist and specialist physicians can
      expect to treat this group of patients, it is important that information about
      the care of transplant patients and their particular problems and needs be made
      more accessible to other physicians. METHODS: The authors have compiled the most
      numerous questions and problems from referring physicians, emergency department
      physicians, and housestaff and have reviewed the recent literature pertinent to
      particular issues. RESULTS AND CONCLUSIONS: This review addresses some of the
      common problems and myths that surround transplant recipients and discusses how
      best to initiate care for these patients, particularly when they seek treatment
      from a nontransplant physician. This review is not exhaustive, but rather a field
      guide to the initial care of this group of patients. The notion that only those
      with specialized knowledge can care for these individuals must now be
      relinquished so that these patients can enter the mainstream of medical care.

PMID- 8285096
TI  - Cogan syndrome: autoimmune-mediated audiovestibular symptoms and ocular
      inflammation.
AB  - BACKGROUND: Cogan syndrome is an uncommon disorder that presents with symptoms
      involving the eyes and ears. At its onset, it can mimic many common entities.
      Family physicians should be aware of Cogan syndrome because it can be
      successfully treated if it is recognized early in its course. It is one of the
      few treatable causes of deafness. METHODS: MEDLINE files were searched from 1982
      to the present for "Cogan's syndrome." Additional references were obtained by
      cross-referencing bibliographies from available articles. RESULTS AND
      CONCLUSIONS: As first defined in 1945, Cogan syndrome includes nonsyphilitic
      interstitial keratitis and attacks of vertigo, tinnitus, and hearing loss.
      Although it usually begins with only one symptom, most patients have both
      auditory and ocular findings within 1 year of the onset. If untreated, most
      patients become deaf within 36 months. Blindness occurs in about 5 percent of
      patients, but ocular symptoms relapse during a period of years. The disease
      eventually involves other organs with clinical and pathologic findings that
      suggest vasculitis. Aortic insufficiency, the most serious complication, develops
      in 15 percent of patients. The cause of Cogan syndrome remains unknown, but
      several studies suggest an autoimmune-mediated process. Many reports document an
      improvement in symptoms with immunosuppressive therapy, particularly if started
      early in the course of the illness. Family physicians should include Cogan
      syndrome in their differential diagnosis when a young adult seeks care with
      audiovestibular symptoms or ocular inflammation.

PMID- 8285097
TI  - Screening and management of cholesterol levels in children and adolescents.
      National Cholesterol Education Program.

PMID- 8285098
TI  - Outcome and cost of family physicians' care--pilot study of three diagnosis
      related groups in elderly inpatients.
AB  - BACKGROUND: Health care analysts have speculated whether a primary-care-based
      delivery system would improve outcomes and costs for the currently preponderantly
      specialist-directed United States system. This pilot study compares outcomes and
      costs of family physicians' care with those of other physicians' care for three
      diagnosis-related groups (DRGs) and shows the feasibility of a larger scale
      research program using the Pennsylvania MedisGroups data base. METHODS: A cross
      sectional comparison of outcomes and costs of hospital care given by either
      family physicians or other physicians was conducted using patients aged 65 years
      and older who were hospitalized during 1990. The study population was 2420
      inpatients: 847 with DRG 174 (gastrointestinal bleeding), 628 with DRG 243
      (medical back pain), and 945 with DRG 296 (metabolic disorders). Patients were
      stratified into five admission severity groups for each DRG. Comparison variables
      were MedisGroups major morbidity classification, in-hospital mortality, mean
      length of stay, and total charges. RESULTS: The family physician group delivered
      inpatient care to the elderly with gastrointestinal bleeding at significantly
      less cost than other physicians without any compromise of effectiveness. There
      was a similar but less striking trend for medical back pain. Results were
      variable for metabolic disorders. CONCLUSIONS: The results of this pilot study
      apply only to the three DRGs in the region at the time investigated.
      Generalizations should be avoided before additional DRGs are studied throughout
      the rest of the state. This pilot study demonstrates the feasibility of such
      research.

PMID- 8285099
TI  - Severe hypothermia associated with prolonged cardiorespiratory arrest and full
      recovery.
AB  - A patient with severe hypothermia was in ventricular fibrillation for more than 1
      hour. Conservative core rewarming methods were used with complete success. In
      dealing with severely hypothermic patients, it is important to continue treatment
      despite prolonged cardiopulmonary arrest. If conservative core rewarming methods
      are not successful, then aggressive invasive techniques might be effective.

PMID- 8285100
TI  - Endometriosis: a part of the differential diagnosis of hip pain.

PMID- 8285101
TI  - Twin vaginal delivery after a previous cesarean delivery for twins.

PMID- 8285102
TI  - Cholesterol: to screen or not to screen, that is the question.

PMID- 8285103
TI  - Cost-effectiveness of care by family physicians.

PMID- 8285104
TI  - Causes of rural hospital closure.

PMID- 8285105
TI  - Cardiovascular risk in a Mennonite community.

PMID- 8285106
TI  - Nondiagnostic colposcopy findings.

PMID- 8285107
TI  - Growth and luminescence of luminous bacteria promoted by agents of microbial
      origin.
AB  - The examination of four species of luminous bacteria Photobacterium leiognathi,
      Photobacterium phosphoreum, Vibrio fischeri and Vibrio harveyi has enabled us to
      reveal some nutrient medium components effecting growth, luminescence intensity
      and luciferase synthesis. These agents are nucleic components (nucleotides,
      nucleotides and amine bases), amino acids and vitamins, which are part of
      hydrolysates from the biomass of various lithotrophic microorganisms, hydrogen
      oxidizing, iron-oxidizing and carboxydobacteria. The effect of promoting agents
      essentially alters the physiological state and ultrastructure of the cells of
      luminous bacteria and increases luciferase biosynthesis two- to three-fold
      compared to a control.

PMID- 8285108
TI  - Luminescence of Ca(2+)-activated photoprotein obelin initiated by NaOCl and
      MnCl2.
AB  - The luminescence of obelin is initiated by NaOCl in a reaction mixture containing
      no calcium. The addition of Mn2+ enhances the light emission > 300-fold. Sodium
      azide and histidine, as singlet oxygen quenchers, inhibit NaOCl-activated obelin
      luminescence in the presence or absence of Mn2+. This suggests that the addition
      of NaOCl to the mixture causes singlet oxygen formation (stimulated by Mn2+
      ions), and singlet oxygen initiates the light-emitting reaction.

PMID- 8285109
TI  - Mechanisms of inhibition of chemiluminescence in the oxidation of luminol by
      sodium hypochlorite.
AB  - Two different mechanisms of inhibition of chemiluminescence in the oxidation of
      luminol by sodium hypochlorite were found. Most substances investigated in these
      experiments acted by scavenging NaOCl. This mechanism was independent of the
      concentration of hydrogen peroxide and the incubation time between luminol and
      inhibitors. The most potent inhibitors were substances containing SH groups.
      Compounds with amino groups as a target for HOCl/OCl- to yield chloramines were
      much less effective inhibitors. Another mechanism of inhibition was found for
      catalase. It depended on the presence of hydrogen peroxide in the incubation
      medium and the incubation time between luminol and catalase. The enzyme inhibited
      the luminescence by removing H2O2 at molar concentrations much smaller than those
      found for all other inhibitors. Our results confirm the present models of the
      mechanism of generation of luminescence in luminal oxidation.

PMID- 8285111
TI  - [The primacy of the clinic].

PMID- 8285112
TI  - [An evaluation of the quality of medical care for hypertensive patients. A review
      of the record of explicit criteria and standards in the clinics of the District
      of Lisbon].
AB  - Cardiovascular and in particular cerebrovascular diseases are the most
      significant in mortality in Portugal, as well as in Lisbon. Arterial hypertension
      is the highest and most prevalent risk factor for cardiovascular diseases, the
      most important predictor of life span and apparently easy to control. A
      descriptive study has been made through observation of the clinical procedures,
      from the record of the explicit normative criteria used in identified
      hypertensive people aged between forty five and sixty four years. From the
      analysis of the results we may confirm that 28% of the studied hypertensive
      individuals had a complete diagnostical process, 48% has a complete following
      process and 41% had controlled arterial hypertension. The possible justifications
      for these values are the adherence of the ill individuals to vigilance, the
      undervalue of risk factors by health professionals or even the fact that the
      family doctor, due to his deep knowledge of the individual, neglects the records
      of the observations already made.

PMID- 8285110
TI  - Chemiluminescence of diglycidyl ether of bisphenol A--norbornene anhydride
      networks.
AB  - Networks were prepared by curing diglycidyl ether of bisphenol A (DGEBA) with
      variable concentrations of norbornene anhydride (NA). Almost completely cured
      samples with anhydride/epoxide (A/E) molar ratios of respectively 0.8, 0.9, 1.0
      and 1.1, and one incompletely cured sample with A/E = 1.0, were studied by
      chemiluminescence in the temperature range 135-220 degrees C, using isothermal
      stationary or non-stationary (atmosphere change) exposures. The comparison of
      kinetic curves of intensity variation reveals: the importance of unreacted
      epoxide groups as sources of highly emissive radical species, the lowering effect
      of oxidation products, and the increasing effect of the decrease of
      macromolecular mobility due to crosslinking in the case of the incompletely cured
      sample. Most of the features of kinetic curves obtained in non-stationary
      experiments are explained in terms of radical formation mechanisms during
      exposure in inert atmosphere. The results show clearly that chemiluminescence is
      due to reactions of peroxy radicals rather than hydroperoxide groups.

PMID- 8285113
TI  - [Berger's disease in childhood. The clinical, laboratory and histological
      aspects. A collaborative multicenter study of the Pediatric Nephrology Section of
      the Portuguese Society of Pediatrics].
AB  - After a multicentric questionnaire, a clinicopathological study was performed
      retrospectively in 35 children with Berger's Disease. The sex ratio was 2.8/1
      (M/F) and the mean age of onset was 8.5 years. Gross hematuria was the presenting
      sign in all the patients, being isolated in 20 and associated with proteinuria in
      the others. 2.3 was mean number of episodes per year and they lasted from 1 to 4
      days in 14 patients and from 5 to 15 in the remaining. In 32 patients the
      episodes were related to a previous respiratory infection and in the meantime 34
      patients had persistent microscopic hematuria. Seric IgA was raised in 67% of the
      patients during the episodes and in 45% between them. The histopathological
      studies demonstrated, by immunofluorescence microscopy, besides mesangial
      deposits of IgA in all the patients, C3 deposits in 17, IgG in 9 and IgM in 5 and
      by optic microscopy 31 cases had mesangial hypercellularity (2 with crescents in
      less than 50% of the glomeruli) and 4 minimal lesions. None of the 35 patients
      developed renal failure (4.6 years mean follow-up).

PMID- 8285114
TI  - [81 cancers of the rectosigmoid junction. Colonic or rectal neoplasms?].
AB  - With the aim of a better understanding of the cancer of the rectosigmoid junction
      the authors studied a series of 245 patients treated in Surgery Department 4 with
      the following distribution according to the localization: 113 in the sigmoid, 81
      in the rectosigmoid junction and 51 in the superior rectum. The percentage of
      cases operated for intestinal obstruction in the rectosigmoid junction (37.0%)
      was higher than those in the superior rectum (7.8%) (p = 0.001) and the
      resectability rate of tumours located in the rectosigmoid junction (44.4%) was
      lower than that of those located in the sigmoid (68.1%) (p = 0.004). In the
      patients submitted to surgical resection the greater percentage of tumours in
      stage A and B (58.3%) and with venous invasion (34.4%) was observed in the
      rectosigmoid junction. Nevertheless, the differences according to the site and
      shape of the tumour, degree of differentiation, stage and venous invasion were
      not statistically significant. The 5-year survival rate in 101 cases submitted to
      resection was higher in patients with tumours in the superior rectum (75.9%) than
      in patients with carcinomas located in the rectosigmoid junction and in the
      sigmoid (51.5% and 36.8%, respectively). In summary, this study supported those
      who consider the rectosigmoid junction cancers as a specific group, based on the
      particular association of the high frequency of intestinal obstruction and the
      low resectability rate, apparently related with a special anatomic localization,
      in a curved segment of the large bowel and suggests that these carcinomas do not
      constitute, in fact, a colo-rectal independent histopathologic entity.

PMID- 8285115
TI  - [Obstructive sleep apneas. A clinical and laboratory study].
AB  - Our study included 42 patients with obstructive sleep apnea (OSAS) confirmed by
      polysomnography. In these patients we investigated the clinical manifestations,
      the results of the laboratory examinations, including polysomnography, ORL
      observations and tests of pulmonary function, as well as the therapeutic results.
      Our patients presented a serious set of symptoms which included excessive daytime
      sleepiness, snoring, obesity, cranio-facial abnormalities, systemic hypertension,
      cardiac arrhythmias, incapacity to work with precocious retirement, marital
      conflicts and high incidence of accidents, namely traffic accidents. An adequate
      treatment, mostly with nasal CPAP (continuous positive airway pressure), induced
      marked relief of the symptoms; some patients had an advantage in surgical
      treatment and weight reduction. OSAS is a frequent entity, affecting mostly male
      adults after the 5th decade. The lack of knowledge about this entity and the
      common social acceptance of some of its cardinal symptoms induces considerable
      delays in its diagnosis. The severity of the symptoms, the personal and social
      risks of excessive daytime sleepiness, the cardio-circulatory effects and the
      risk of sudden death during sleep justify an early diagnosis in order to prevent
      the severe evolution of the disease. Its complex physiopathology and multiple
      etiological factors justify a multidisciplinary approach.

PMID- 8285116
TI  - [Postmortem orbital hematomas].
AB  - Several cases of post mortem hematoma resulting from harvesting of the eye globes
      for transplantation, and susceptible of being misinterpreted as representing ante
      mortem trauma, are presented. Based on these cases the authors make a few
      considerations about the mechanisms of their production and technical procedures
      to avoid them.

PMID- 8285117
TI  - [Essential thrombocythemia. Apropos a case of cerebrovascular stroke].
AB  - The authors report the case of a 60-year-old white man with a previous history of
      pulmonary tuberculosis, smoking habits, hypertension, intermittent claudication
      and erythromelalgia, admitted to our ward with an ischemic cerebral event.
      Initial laboratory evaluation documented thrombocytosis (platelet-950000/mm3) and
      discrete anemia. Additional studies confirmed the diagnosis of essential
      thrombocythemia, meeting all the criteria proposed by the Polycythemia Vera Study
      Group in 1986, after exclusion of the possible causes of reactive thrombocytosis.
      Therapy was initiated with alpha-2b interferon (3 MU/m2 subcutaneously three
      times a week) and aspirin. Platelet count control was obtained and the patient
      remained asymptomatic. Nine months later cutaneous toxicity obliged the
      discontinuance of alpha-interferon. Due to a continuous increase of platelet
      count, hydroxyurea was introduced. The patient is asymptomatic, with platelet
      counts < 500000/mm3, without toxicity manifestations, two years after diagnosis.
      The contribution of cardiovascular risk factors versus thrombocythemia in the
      pathogenesis of the ischemic cerebral event and the benefit of platelet count
      control are discussed.

PMID- 8285118
TI  - [Cefoxitin: its role in the therapy of anaerobic infections].
AB  - Cefoxitin is a second generation cephalosporin commonly used to treat anaerobic
      and mixed infections. The authors reviewed the recently published data about the
      efficacy of cefoxitin; its utility in different clinical entities, patterns of
      resistance and resistance mechanisms, indications and reliability of in vitro
      susceptibility testing. These data indicate the need for determining
      susceptibility patterns of anaerobics at each hospital and point out to the
      essential close communication between the microbiologist and clinician to the
      rational treatment of anaerobic infections.

PMID- 8285119
TI  - [Acute promyelocytic leukemia. The therapeutic advances].
AB  - Acute promyelocytic leukemia (APL) is a rare subtype of acute myelogenous
      leukemia. It is frequently associated with a life-threatening hemorrhagic
      diathesis, often aggravated by induction cytotoxic chemotherapy. Patients with
      APL have bone marrow infiltration by abnormal promyelocytes, usually with
      prominent cytoplasmic granulation. These patients have a unique cytogenetic
      abnormality, a balanced reciprocal translocation between the long arms of
      chromosomes 15 and 17. The nuclear retinoic acid receptor alpha gene, on
      chromosome 17, is translocated to the PML gene region, on chromosome 15,
      resulting in the synthesis of two fusion messenger ribonucleic acids, PML/RAR
      alpha and RAR-alpha/PML, easily detected by the reverse transcriptase polymerase
      chain reaction. This assay is extremely useful in the diagnosis and detection of
      minimal residual disease in APL patients. All trans-retinoic acid (ATR)
      differentiates the malignant cell clone and corrects the coagulopathy associated
      with this disease. The most important adverse effect is a respiratory distress
      syndrome, treatable with steroids, if detected at its onset. ATR yields durable
      remissions in patients with APL, after consolidation with cytotoxic chemotherapy.

PMID- 8285120
TI  - [The directional axes in the reform of medical teaching. A strategic proposal].
AB  - The circumstances preceding the future revision of the medical curriculum are
      analysed, main internal and external stimuli are described, and sources of
      resistance to changes in medical training require new educational philosophy,
      privileging oriented training during undergraduation, as a preliminary phase of
      medical education. The definition and accompaniment of the general and specific
      objectives, the strategy and programme used, the design and adequacy of the
      available support, and the related engagement of all political, academic and
      socially responsible persons and institutions, are fundamental factors for
      successful change. The education and training of polyvalent medical doctors
      requires methodological modifications, namely the definition of a core
      curriculum, made dynamic through the teaching of interdependent subjects and
      earlier contact with common clinical problems. Learning through interconnected
      basic and clinical matters will benefit the technical and psychosocial education
      of future doctors. The education resulting from a renewal in undergraduate
      medical education will be mostly determined by organizational and institutional
      frameworks, teaching methods and the evaluation process used, as well as by
      teacher commitment, pedagogic and scientific capacities. Professional competence
      should be the end product of efficient training. Otherwise, undergraduate medical
      education would not prepare the professional development of the young doctors,
      thus diminishing the quality of medical training in the future.

PMID- 8285121
TI  - [A single-topic supplement on prenatal cardiology].

PMID- 8285122
TI  - [Fetal cardiology. Bases for the prenatal diagnosis of congenital cardiopathies].
AB  - The bases for prenatal diagnosis of congenital heart disease are presented, in
      the line of a comprehensive program undertaken by paediatric cardiology and
      obstetrics. This program is designed to improve the screening of fetal heart
      diseases by obstetric echographists, particularly those working at peripheral
      high risk clinics. It includes the visit of paediatric cardiologists to district
      hospitals for joint meetings with local physicians, going over theoretical
      aspects, case presentation and four chamber view with outflow tract
      demonstrations using local ultrasound equipment. Referring protocols, handouts
      and support media exchange are contemplated. Support texts on the program
      divulged, on etiology of congenital heart disease, on abnormal fetal
      echocardiography and on fetal dysrhythmias are presented here in. The need for an
      organized national effort to increase the prenatal diagnosis of congenital heart
      disease is emphasized as well as the need to centralize some aspects related to
      diagnosis and treatment in order to improve the care of newborns with congenital
      heart disease.

PMID- 8285123
TI  - [General concepts on the etiology of congenital cardiopathies].

PMID- 8285124
TI  - [Transvaginal endosonography and Doppler study in embryo-fetal hemodynamic
      assessment in the first pregnancy trimester].
AB  - Transvaginal endosonography is now currently used in obstetrics and gynecology
      practice and seems a promising tool for essential studies on first trimester
      pregnancy. High-resolution and duplex/color Doppler in vaginal probes have
      brought to light new chances for early investigations on embryonic-fetal
      haemodynamics. We report our experience in this field, together with a review of
      the literature, giving an overview on embryonic-fetal cardiovascular
      haemodynamics studied by this approach. Blood flow patterns of intracardiac flows
      as extra-cardiac circulation during first trimester pregnancy are reported.

PMID- 8285125
TI  - [The plan of the 4 heart chambers and the ventricular outflow tracts. A simple
      echocardiographic method for the diagnosis of cardiopathies in the fetus].

PMID- 8285126
TI  - [Fetal arrhythmias. The general concepts].

PMID- 8285127
TI  - [Fetal echocardiography. The results of a 3-year study].
AB  - During the last three years (July 89 to July 92), 875 fetal echocardiographic
      studies were performed, at a mean gestational age of 26 +/- 6.5 weeks (12 to 40
      weeks), with the following main referral indications: family history of
      congenital heart disease 23%; advanced maternal age 13%; fetal arrhythmia 10%;
      amniotic fluid abnormalities 8%; fetal malformations 7%; diabetes 6%; four
      chamber view changes 4%. There were 15 twin pregnancies, two of them
      thoracopagus. The referral patterns with higher percentage of cardiac pathology
      were: abnormal four chamber view 56%; fetal chromosomal anomalies 50%;
      omphalocele 33%; twin pregnancy 33%; IUGR 29%; arrhythmias 20%. The referral
      patterns with lower percentage of cardiac pathology were: congenital heart
      disease in the family 0.2%; maternal risk 2%; amniotic fluid volume alterations
      2%. The diagnosis of congenital heart disease was made in 37 fetus (4.2%), with
      the following most frequent: 9 cases with the atrioventricular septal defect, 5
      cases with ventricular septal defect, 5 cases with hypoplastic left heart
      syndrome and 5 cases with tricuspid valve abnormalities. From a total of 78
      referred fetal arrhythmias, 25 were confirmed, 20 being ectopic beats without
      structural heart disease, 3 with tachycardia, and 2 with bradycardia. One newborn
      with tachycardia and Ebstein's disease died, and the fetus with AV block and left
      atrial isomerism died in utero. The treatment and follow up of the remaining
      cases with heart disease are described. The whole mortality in the cases with
      heart pathology was 65%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285128
TI  - Immunological and biochemical investigations of infectious bovine
      rhinotracheitis. IV. Effect of suramin on pulmonary surfactant lipids.

PMID- 8285129
TI  - Effect of oxadiarrhot on some mechanisms of the immune system.
AB  - The preliminary application of the preparation Oxadiarrhot has no effect on the
      progress and the result of bacterial and mixed (bacterial-viral) infections. In
      animals treated with the preparation antigen-reactive and antibody-productive
      cells show insignificant decrease in number. There is no essential influence of
      the preparation on the mononuclear phagocytes system--the alveolar macrophages
      and polymorphonuclears do not change their functions.

PMID- 8285130
TI  - Studies on aerosol Yersinia pseudotuberculosis infection of guinea-pigs.
AB  - Aerosol Y. pseudotuberculosis infection in guinea-pigs has been reproduced. In
      the course of infectious process, alveolar macrophages respiration is activated
      due to a rise in their cytochrome oxidase activity.

PMID- 8285131
TI  - Combined effect of selected antiviral substances of natural and synthetic origin.
      II. Anti-influenza activity of a combination of a polyphenolic complex isolated
      from Geranium sanguineum L. and rimantadine in vivo.
AB  - The synergistic effect shown by the combination of a natural product,
      polyphenolic complex (PC) isolated from Geranium sanguineum L., and rimantadine
      (R) in vitro and in ovo [7], encouraged us to continue these studies by in vivo
      testing. A marked protective effect in experimental influenza virus A (H3N2)
      infection in mice was found when PC was applied nasally (i.n.) (1.0 mg/kg) only
      once 6 h before infection in combination with R applied orally in concentration
      10.5 and 2.5 mg/kg 2h before and 2.24 and 48 h after viral inoculation (PI =
      72.55%, 55% and 57.8% respectively).

PMID- 8285132
TI  - Amylase activity of Aspergillus strains--producers of organic acids.
AB  - The ability of fungi from genus Aspergillus (producers of organic acids) to
      synthesize amylase enzymes (alpha-amylase and glucoamylase) was investigated. The
      productivity of the strains on Czapek-Dox agar and in liquid Czapec-Dox media
      with 3% soluble starch as a carbon source was established.

PMID- 8285133
TI  - Kinetics of the gluconic acid biosynthesis by strain Aspergillus niger 13-73.
AB  - The kinetics of gluconic acid biosynthesis of the strain Aspergillus niger 13-73
      by submerged cultivation in a medium containing 26% glucose was investigated. The
      maximum amount of the product was obtained at minimum biomass growth. The yield
      of the product compared to the theoretical one was 95% and the fermentation
      period was 42 hours. The results regarding the limitation theory are discussed.

PMID- 8285134
TI  - Biodegradation of dimethylterephthalate by mixed microbial cultures.
AB  - The microbial association 189 was isolated from soil treated with
      dimethylterephthalate (DMT) for a long time. The dynamics of its growth,
      respectively the degradation of the terephthalate ester known as an environmental
      pollutant has been studied.

PMID- 8285135
TI  - Influence of some physicochemical factors on dimethylterephthalate
      biodegradation.
AB  - The mixed microbial culture 189 possesses high biodegradation capacity against
      dimethylterepthalate (DMT)--a basic substance in polyester fibres production and
      an environmental pollutant. The process of its degradation was followed and the
      effect of some external factors (pH, concentration, accompanying substrates) on
      the growth of the association was shown.

PMID- 8285136
TI  - Lung inflammatory cells after exposure to mouldy hay.
AB  - To investigate the inflammatory cell response after exposure to mouldy hay,
      guinea pigs were exposed to an aerosol of spores from mouldy hay. Lung wall (LW)
      and lung lavage (LL) cells were counted after 5 weeks of daily exposures. At 5
      weeks both LW and LL macrophages, lymphocytes and neutrophils increased. The LL
      cell increase was proportionally higher. At 12 weeks, the increase in the number
      of cells was slightly less than at 5 weeks. After cessation of exposure,
      macrophages and lymphocytes remained elevated up to 7 days whereas neutrophils
      rapidly decreased to normal values. This animal inhalation model of early
      allergic alveolitis could be used to evaluate the importance of different
      exposure conditions and various agents in the dust.

PMID- 8285137
TI  - Mustard oil-induced cutaneous inflammation in the pig.
AB  - Recent findings indicate that chemical stimulation of the porcine skin with
      capsaicin evokes a flare response similar to that observed in man. The aim of the
      present study was to elucidate whether chemical stimulation of cutaneous
      capsaicin-sensitive nerve endings with mustard oil produces neurogenic
      inflammatory reactions in the pig. The application of mustard oil onto the
      abdominal skin of domestic pigs resulted in a pronounced flare response. After a
      previous intravenous injection of a solution of Evans blue, the skin area in
      contact with the irritant turned dark blue, indicating a marked extravasation of
      albumin. Quantitative estimation of the dye content of the skin supported this
      conclusion. The technique of vascular labelling revealed a delicate network of
      small subepidermal blood vessels in histological preparations after the
      application of mustard oil following a previous intravenous injection of
      colloidal silver. Labelled blood vessels were not noted outside the treated area.
      The present results show that mustard oil produces a strong cutaneous
      inflammatory response in the pig, and suggest that the porcine skin provides a
      valuable model for study of the significance of capsaicin-sensitive sensory
      nerves in vascular and other cutaneous reactions.

PMID- 8285138
TI  - Effects of two vasodilatory phosphodiesterase inhibitors on bradykinin-induced
      permeability increase in the hamster cheek pouch.
AB  - Two inhibitors with selective effect on cyclic nucleotide phosphodiesterases
      (PDEs, preferentially hydrolyzing cAMP), milrinone (cGMP-inhibited PDE) and
      rolipram (cAMP-specific PDE) were studied for their effects on bradykinin-induced
      plasma leakage in comparison with the beta 2-receptor stimulant terbutaline. The
      dilation of arterioles induced by milrinone and rolipram was studied in the
      concentration range 10(-7)-10(-4) M. Maximal arteriolar dilation was 53% for
      milrinone at 10(-4) M and 28% for rolipram at 10(-4) M. The hamster cheek pouch
      preparation was used as prepared for intravital microscopy of fluorescein
      labelled dextran, FITC-dextran. Bradykinin was applied topically to the cheek
      pouch at a final concentration of 4 x 10(-7) M and caused rapid and reversible
      increase in plasma leakage (number of leakage sites) from postcapillary venules.
      Milrinone (M), rolipram (R) and terbutaline (T) were also applied topically
      starting 5 min prior to bradykinin application and at final concentration of 10(
      4) and 10(-5) M (M), 10(-5) and 10(-6) M (R) and 10(-7) M (T). These local
      concentrations resulted in significant (p < 0.05) and reversible inhibition of
      the bradykinin-induced response by 44% and 33% (M), 77% and 67% (R) and 46% (T).
      Combining M and R individually with T resulted in a significantly larger
      inhibition of the bradykinin response than with each of the drugs given
      separately.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285139
TI  - Effects of a highly selective plasma kallikrein inhibitor on collagen-induced
      arthritis in mice.
AB  - A study was conducted to evaluate the effects of a new, highly selective plasma
      kallikrein inhibitor, PKSI-527, on collagen-induced arthritis (CIA) in mice. PKSI
      527 or indomethacin was administered daily intraperitoneally from day 20
      postimmunization. Clinical evaluation was performed, and two of the components of
      the kallikrein-kinin system, high-molecular-weight (HMW) kininogen and plasma
      prekallikrein, were assayed. PKSI-527, as well as indomethacin, reduced the
      severity of arthritis significantly. PKSI-527, but not indomethacin, restored
      consumed components of the kallikrein-kinin system. These results suggest that
      PKSI-527 suppresses CIA by modifying the kallikrein-kinin system and PKSI-527 as
      a synthetic plasma kallikrein inhibitor would be a valuable tool to study the
      mechanism of inflammation of arthritic diseases.

PMID- 8285140
TI  - Is aspirin a prodrug for antioxidant and cytokine-modulating oxymetabolites?
AB  - Aspirin and salicylate are transformed by stimulated human polymorphonuclear
      leucocytes (PMN), likely to be found at inflammatory sites, into both 2,3- and
      2,5-dihydroxybenzoates (DHB). These DHB inhibit both the production of hydrogen
      peroxide by stimulated human PMN and prostaglandin (PG) E2 by activated rat
      macrophages. In contrast, DHB stimulated production of interleukin (IL)-1 and
      tumour necrosis factor (TNF) but inhibited IL-6 production by rat macrophages.
      These effects were probably a consequence of PGE2 inhibition. Gentisate (2,5-DHB)
      and homogentisate (a tyrosine metabolite) inhibited the lymphoproliferative
      action of IL-1. Some related phenols, e.g. 5-aminosalicylate, inhibited H2O2
      production but had little effect on PGE2 production. These findings suggest that
      the local synthesis of DHB may contribute to the overall anti-inflammatory
      activity of salicylate, which (unlike aspirin) has little direct effect on PG
      production.

PMID- 8285141
TI  - Pharmacokinetics of tiaprofenic acid in normal rabbits and rabbits subjected to
      joint immobilisation.
AB  - In a previous study, tiaprofenic acid (TA) was administered daily over a 30-day
      period at 5 and 10 mg/kg of body weight subcutaneously (s.c.) to animals with
      arthritis induced by immobilisation. The 10 mg/kg dose exacerbated the loss of
      proteoglycan from joint cartilage but the 5 mg/kg dose showed protective effects
      on articular cartilage. These results led us to investigate the concentration of
      TA achieved in synovial fluid of both the immobilised and non-immobilised rabbit
      joints after single s.c. doses of 5 or 10 mg/kg. The half-lives of elimination of
      TA from the synovial fluids of the immobilised joints were 1.27 and 1.07 h after
      the 5 and 10 mg doses, respectively, and 0.66 and 0.39 h in the non-immobilised
      contralateral joints. Clearances from synovial fluid to plasma were found to be
      0.41 and 0.55 ml/h/kg from the immobilised joints after the 5 and 10 mg doses,
      respectively, and 0.11 and 0.25 ml/h/kg from the non-immobilised contralateral
      joints. The peak concentration of TA achieved in synovial fluid of immobilised
      knee joints after a single s.c. injection of 10 mg/kg was approximately two times
      greater than the concentrations achieved after administration of 5 mg/kg by the
      same route and two to six times greater than the levels achieved after oral
      administration of TA at 600 mg/day in humans.

PMID- 8285142
TI  - Some problems with the diamine oxidase (DAO) assay using putrescine as substrate
      in rat liver.
AB  - Determination of diamine oxidase (DAO) activity in rat liver preparations by
      measuring the formation of radioactive delta 1-pyrroline from 14C-putrescine is
      complicated by the complexity of competing metabolic pathways. This can lead to
      complete masking of the DAO activity present when rat liver homogenates are used
      as the enzyme source. However, subcellular fractionation of rat liver homogenates
      makes it possible to detect some putrescine oxidizing activity in the microsomal
      fraction when assayed at pH 8.5. When 1 mM putrescine was used as the substrate,
      over 90% of this activity was inhibited by 6 x 10(-4) M selegiline (deprenyl),
      indicating that monoamine oxidase (MAO) rather than DAO activity was being
      measured. The observed activity was also interfered with by agents that reduced
      acetylation processes and polyamine synthesis. A different picture appears when
      microM concentrations of putrescine are used: in these conditions all
      interference is strongly reduced and DAO activity can be measured in rat liver
      microsomes. Furthermore, kinetic studies on deaminative oxidation of 14C
      putrescine at concentrations from 1 microM to 5 mM confirm the existence of two
      enzymes: one with a high affinity for the substrate and similar to intestinal
      mucosa DAO in its sensitivity to alpha-aminoguanidine, and the other one with a
      low affinity and selegiline-sensitive.

PMID- 8285143
TI  - In vitro activation of hepatic glutathione reductase from mice by lobenzarit
      disodium.
AB  - Glutathione reductase activity from mice liver is significantly enhanced by
      lobenzarit disodium at concentrations between 0.3 and 1.5 mM. A maximum
      activation of almost 30% is achieved at a drug concentration of 0.9 mM. Similar
      results were observed with glutathione reductase from human leukocytes, but not
      with the enzyme from yeast. By preincubation with the enzyme from mice liver,
      lobenzarit also proved to prevent, at least partially, the immediate inhibition
      caused by the well-known thiol-reacting agents, thus indicating a protecting
      effect on the catalytically important thiol residue of the enzyme. The results
      here obtained explain in part the recently found hepatoprotective effect of
      lobenzarit disodium against acute liver toxicity induced by acetaminophen in
      mice.

PMID- 8285144
TI  - The removal of metal ions from transferrin, ferritin and ceruloplasmin by the
      cardioprotective agent ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane]
      and its hydrolysis product ADR-925.
AB  - The ability of the metal ion binding rings-opened hydrolysis product of the
      anthracycline cardioprotective agent ICRF-187 [dexrazoxane; (+)-1,2-bis(3,5
      dioxopiperazinyl-1-yl)propane] to remove iron from transferrin and ferritin, and
      copper from ceruloplasmin was examined. ADR-925 completely removed Fe3+ from
      transferrin at below physiological pH but was unreactive at pH 7.4. ADR-925
      slowly removed copper from ceruloplasmin at physiological pH (68% removal after
      4.8 days). ADR-925 was capable of removing 18% of the iron from ferritin in 7.0
      days. All of the metalloproteins displayed saturation behavior in their initial
      rates of metal ion removal by ADR-925. ICRF-187 may be, in part, preventing
      doxorubicin-induced cardiotoxicity by depleting iron and copper from these
      storage and transport proteins or by scavenging metal ions released from these
      proteins, thus inhibiting hydroxyl radical production by iron-doxorubicin
      complexes.

PMID- 8285146
TI  - [Molecular cloning of the genes in genetic chorioretinal diseases--positional
      cloning and the candidate gene approach].
AB  - Two different molecular biological approaches to the disease-causing genes of
      genetic eye diseases are described. In gyrate atrophy of the chroid and retina
      where the biochemical defect was identified as inactivation of ornithine
      aminotransferase, the gene was cloned by using antibody for the enzyme. In most
      genetic eye diseases, however, the biochemical defects are unknown. Positional
      cloning and/or the candidate gene approach are used to identify the disease
      causing genes for these diseases. The genes of chroideremia and Norrie disease
      were cloned by positional cloning. Several genes expressed in the photoreceptor
      cells have been identified recently and may be the genes causing progressive
      degeneration of the retina and choroid. Rhodopsin, peripherin (RDS), rom-1, and
      beta subunit-cGMP phosphodiesterase are identified as the disease-causing genes
      for retinitis pigmentosa by the candidate gene approach.

PMID- 8285145
TI  - Independent effects of interleukin 1 on proteoglycan synthesis and proteoglycan
      breakdown of bovine articular cartilage in vitro.
AB  - We studied the effects of human recombinant interleukin-1 beta on proteoglycan
      metabolism of bovine articular cartilage in organ culture. IL-1 was more potent
      in inhibiting synthesis (IC50 4 ng/mL) than in stimulating breakdown of
      proteoglycans (EC50 200 ng/mL). Inhibition of proteoglycan synthesis began to
      plateau earlier (2 days) than stimulation of proteoglycan release (4 days). Both
      effects could be neutralized with a polyclonal anti-IL-1 beta antibody; however,
      higher antibody titers were required to block IL-1 effects on proteoglycan
      synthesis than to neutralize those on proteoglycan release. Chloroquine, but not
      hydrocortisone, blocked IL-1-mediated proteoglycan breakdown. Both drugs,
      however, augmented IL-1-induced inhibition of proteoglycan synthesis. Our data
      suggest that the effects of IL-1 on articular cartilage proteoglycan synthesis
      and proteoglycan breakdown can be regulated independently.

PMID- 8285147
TI  - [Histological analysis of aging ciliary body].
AB  - The aging changes in human ciliary body were studied by histological analysis.
      Thirty four autopsy eyes were fixed in 2.5% formalin and 1.0% glutaraldehyde
      mixture. The age distribution was 12 eyes below 50 years of age 13 eyes between
      60 and 70 years of age, and 9 eyes over 80 years of age. Serial sections of the
      ciliary body were made parallel to the limbus and vertical to the ciliary
      processes. From four areas (transitional portion between pars plana and pars
      plicata, posterior portion of pars plicata, middle portion of pars plicata, and
      anterior portion of pars plicata) a central section was selected. Histological
      analysis was done with the use of Azur II stained light microscopic pictures. The
      basement membrane of non-pigmented epithelium below 50 years of age was thinner
      than between 60 and 70 years of age. This finding may be related with lowering
      aqueous humor secretion with aging. Non-pigmented epithelium, blood vessels in
      the stroma, and muscle fibers in muscle tissue showed aging changes. The pigment
      epithelium, basement membrane, and muscle fibers in muscle tissue did not show
      aging changes in light microscopical analysis, but study of their fine structure
      is necessary.

PMID- 8285148
TI  - [Damage to cultured corneal endothelium caused by ultrasound during
      phacoemulsification].
AB  - An experimental study was performed to estimate the degree of corneal endothelial
      damage caused by ultrasound during phacoemulsification. Cultured corneal
      endothelium prepared from bovine eyes was exposed to ultrasound. Dead cell rates
      were determined by counting the number of cells positively stained by trypan blue
      under various conditions of ultrasonic radiation. Dead cell rate increased from
      13 +/- 2% to 39 +/- 4% (n = 5, Mean +/- S.D.) as ultrasonic duration was
      prolonged from 15 seconds to 45 seconds. Dead cell rate increased from 6 +/- 1%
      to 39 +/- 4% as ultrasonic power increased from 60% to 100%. Dead cell rate
      increased from 8 +/- 1% to 44 +/- 11% as the distance of the phaco tip decreased
      from 7 mm to 4 mm. Dead cell rate increased from 4 +/- 2% to 35 +/- 7% as the
      angle of the phaco tip increased from 30 degrees to 90 degrees. We confirmed that
      endothelial damage depended on ultrasonic duration, ultrasonic power, the
      distance of the phaco tip, and the angle of the phaco tip. We suggest that the
      endothelium is damaged mainly by shock waves emanating from the phaco tip.

PMID- 8285149
TI  - [Scanning electron microscopic observation of hydrodissected human lens nucleus].
AB  - Using a scanning electron microscope, we studied the surface structure of 5
      different central nuclei, isolated by repeated hydrodissection during
      extracapsular cataract extraction. Aside from the damage induced by surgical
      maneuvers, the surfaces were very smooth, and there was no major disruption of
      the lamellar structure of the lens. Our studies have shown that hydrodissection,
      which allows atraumatic separation of the lens fiber layers, can be used to
      analyze the lamellar structure of the lens. Some of the evaluated specimens
      showed a distinct suture line and the lens fibers were approximately at right
      angles to it. These observations were different from those reported previously.

PMID- 8285150
TI  - [Anatomical evaluation of hydrodissected human lens nucleus].
AB  - We measured the diameter and central thickness of the central nucleus, isolated
      by repeated hydrodissection, in 100 eyes undergoing extracapsular cataract
      extraction. The average diameter and central thickness were 6.43 +/- 0.86 mm and
      2.93 +/- 0.36 mm, respectively. The average ratio between the two measurements
      was 2.12, which is similar to that of an extracted crystalline lens. Statistical
      analysis revealed a positive correlation between central thickness and age (p <
      0.05). There was a weak positive correlation between central thickness and
      hardness of the nucleus. Since specimens were obtained from clinical cases in
      this study, further evaluation should be made using cadaver eyes.

PMID- 8285151
TI  - [The effect of epidermal growth factor on the growth potential of epithelial
      cells from human lens].
AB  - The growth promoting effect of epidermal growth factor (EGF) was studied in
      cultures of epithelial cells from human normal and cataractous lenses. The growth
      potential of lens epithelial cells was measured by MTT assay. The concentration
      of EGF in culture medium were classified into 7 groups (0 ng/ml-10(3) ng/ml).
      When the concentration of EGF was 1 ng/ml, EGF induced the highest increase of
      growth potential epithelial cells compared with an EGF-free group.

PMID- 8285152
TI  - [Intraocular lens implantation in severely mentally and physically handicapped
      patients].
AB  - We implanted a posterior chamber intraocular lens (PC-IOL) in 30 eyes of 17
      severely mentally and physically handicapped patients, i.e., 14 eyes of 9
      severely mentally retarded patients, 14 eyes of 7 patients with Down's syndrome,
      and 2 eyes of a mitochondrial encephalomyopathy patient. All surgery was
      performed under general anesthesia and 3 to 10 post-operative days of hospital
      care were needed in an ophthalmic ward. A post-operative intensive care unit was
      not necessary. Severe post-operative complications occurred in 2 eyes of 2 cases.
      One case was complicated by an iris prolapse, and in another case traumatic wound
      rupture caused a prolapse of the IOL, vitreous, and retina. However, in both
      cases, the other eye, which also had a PC-IOL implantation, showed an uneventful
      post-operative course. Vision and quality of life in all patients seem to have
      improved. The present observations indicate that cataract surgery with PC-IOL for
      these patients should be positively considered in spite of difficulties in pre-
      and post-operative management, and when done, calibration of IOL power
      immediately before surgery under general anesthesia and small incision techniques
      are essential.

PMID- 8285153
TI  - [Eye movements in dissociated vertical deviation].
AB  - The horizontal, vertical and cyclorotational components of eye movements were
      analyzed in 8 cases of dissociated vertical deviation (DVD), using a Fundus
      Haploscope (Inatomi, 1980) and an Eye Movement Analyzing System (Kani, 1985).
      Excyclomovements and upward movements were observed in the deviating eyes in all
      cases, and incyclomovements in the fixating eyes in 6 cases. Sequential analysis
      revealed these movements to be "cycloversion". Vertical movements and
      cyclorotational movements were similar in their forms, but in some parts only the
      torsional movements were recognized. The rotatory nystagmus of patients'
      binocular vision efforts were almost purely rotatory, of the pendular type, and
      seemed to have congenital nystagmus characteristics. Many kinds of abnormal
      cyclorotational movements were found in these DVD cases. These movements were all
      version movements. Cyclorotational movements in DVD cases were thought to reflect
      abnormalities in the upper levels of the central nervous system. Abnormalities of
      the "cyclorotational movement center" were assumed in DVD.

PMID- 8285154
TI  - [The central visual field defects in low-tension glaucoma. A comparison of the
      central visual field defects in low-tension glaucoma with those in primary open
      angle glaucoma].
AB  - To discover if there is difference in central visual field damage between low
      tension glaucoma (LTG) and primary open angle glaucoma (POAG) eyes, the data
      obtained with the 10-2 threshold program of the Humphrey visual field analyzer
      were analysed using logistic discriminant analysis. One hundred and four LTG eyes
      from 65 case (maximum IOP < or = 21 mmHg) and 48 POAG eyes from 34 cases (maximum
      IOP > or = 25 mmHg) with early to moderately advanced visual field damage were
      included. There was no significant difference in mean deviation (MD, STATPAC),
      refraction, or age between the 2 groups. The analysis demonstrated that an
      arcuate area in the upper central 5-10 degrees of the visual field was
      significantly more depressed in LTG than in POAG eyes.

PMID- 8285155
TI  - [Optical density of human macular pigment in spectral sensitivity measurements].
AB  - Optical density of the human macular pigment was measured by studying the
      spectral sensitivities to 1 degree, 200 ms test flashes on a 430 nm monochromatic
      background in the fovea and 10 degrees outside the fovea. Narrow-band (6 to 10 nm
      half band width) interference filters were used for the test lights. The
      difference between the spectral sensitivity in the fovea and outside the fovea
      coincided with the optical density of the macular pigment estimated previously by
      psychophysical means. We suggest that this method is useful for investigating the
      optical density of human macular pigment.

PMID- 8285156
TI  - [Lattice corneal dystrophy type II with familial amyloid polyneuropathy type IV].
AB  - Lattice corneal dystrophy type II associated with familial amyloid polyneuropathy
      type IV (Finish type, FAP-IV) has not yet been reported in Japan. We report 7
      cases in a Japanese family. The proband, a 64-year-old man, suffering from
      itching in his limbs, impaired lip movement, and dysarthria, consulted the
      Department of Neurology, University of Tokyo. Neurological examination revealed
      bilateral facial, glossopharyngeal, vagal, and hypoglossal nerve palsy, and
      impaired distal vibratory perception. His vision was 1.2 and he had fine lattice
      corneal dystrophy in both eyes. Short glassy lines were randomly scattered in the
      lattice dystrophy. Corneal sensation was normal and there was no evidence of
      recurrent corneal erosion. Immunohistological and biochemical studies confirmed
      the diagnosis of FAP-IV. Six siblings were neurologically suspected to be FAP-IV
      patients with similar lattice corneal dystrophy. The family pedigree suggested an
      autosomal dominant trait of inheritance.

PMID- 8285157
TI  - [A case of necrotizing scleritis associated with Epstein-Barr virus infection].
AB  - Recently Epstein-Barr virus (EBV) is often reported in association with ocular
      disease. But EBV has not been reported to cause necrotizing scleritis. A 71-year
      old woman developed ciliary injection and peripheral corneal ulcer in both eyes.
      The lesions did not respond to topical steroid and systemic indomethacin. The
      sclera became transparent and perforated. EBV serologic antibody titers were
      strongly positive. Anti-viral capsid antigen (VCA)-IgG was 1: 1,280 and anti
      early antigen (EA)-IgG was 1: 640. These serologic results suggested active EBV
      infection. Using immunofluorescence techniques, the squamous epithelial cells of
      the conjunctiva were stained with monoclonal antibody against EBV-VCA and
      strongly stained with antibody against IgG. The results of serologic test and the
      immunofluorescence techniques appeared to suggest that the necrotizing scleritis
      was caused by EBV.

PMID- 8285158
TI  - [Benign hemorrhagic renal cyst mimicking cystic renal cell carcinoma].
AB  - We experienced four cases of benign hemorrhagic renal cyst which were
      indistinguishable from cystic renal cell carcinoma on ultrasonography, computer
      tomographic scanning, magnetic resonance imaging and angiography. Nephrectomy was
      performed in one case and enucleation of the mass in the other three.
      Pathological diagnoses were hemorrhagic septate cyst in two cases, cyst with
      inflammation containing old blood clots in one, and organized hemorrhagic cyst
      with calcification in one. Conservative surgeries should be considered when the
      definite diagnosis for renal hemorrhagic cysts is not made.

PMID- 8285159
TI  - [Septic shock induced by extracorporeal shock wave lithotripsy treatment with
      percutaneous nephrostomy in 5 cases with urolithiasis].
AB  - We have experienced 5 cases of septic shock induced by extracorporeal shock wave
      lithotripsy (ESWL) and percutaneous nephrostomy. We suspected 5 causes of septic
      shock; severe hydronephrosis, nephrostomy tube itself, an increase of intrarenal
      pressure, bacteria in urinary stone, and hepatic failure. Based on the above
      suspected causes of septic shock, we suggested 3 prophylactic treatments for
      septic shock; a preventive administration of antibiotics before ESWL and
      percutaneous nephrostomy, proper management of nephrostomy tube, and early
      diagnosis and treatment for septic shock.

PMID- 8285160
TI  - [Diagnostic imaging of invasive renal pelvic cancer].
AB  - In 5 patients with invasive renal pelvic cancer, we evaluated the imaging
      features of drip infusion pyelography (DIP), retrograde pyelography (RP),
      ultrasonography (USG), computerized tomography (CT), magnetic resonance imaging
      (MRI) and renal angiography (RAG). The different features of high diagnostic
      value were as follows. DIP revealed no visualization with enlargement and
      reniform outline. RP revealed irregular, serrated filling defect of the pelvis
      with destruction of the involved calyces and infundibula. USG revealed loss of
      normal parenchymal architecture with amputation of the central echo complex due
      to echogenic mass. CT revealed widened renal parenchyma and the involved
      parenchymal segment, which was replaced by tumor mass with inhomogeneous density
      and minimal enhancement. MRI denoted renal vein thrombus. RAG revealed, besides
      the fine neovascularity with tumor blush, hypovascularity in the involved area.
      In addition to these features, we believe that in particular, RP, USG, CT and RAG
      are useful tools for patients with non-functioning kidney.

PMID- 8285161
TI  - [Clinical observations on bladder cancer--difference in clinical features with
      age].
AB  - Three hundred and ninety-four patients with transitional cell carcinoma of the
      bladder who initially visited Yokohama City University Hospital were reviewed
      according to age group. The patients were divided into four groups, group A (less
      than 49 years old), group B (from 50 to 64 years old), group C (from 65 to 79
      years old) and group D (more than 80 years old). The clinical characteristics as
      follows were obtained by statistical analysis compared with these four groups. No
      statistical significance was obtained about frequency of macroscopic hematuria as
      chief complaint. However, the younger age groups (A and B) tended to visit
      hospital later after the first symptom of hematuria. The older age groups (C and
      D) had multiple and large tumor at the first cystoscopic examination. The older
      age groups (C and D) had high stage and high grade tumor at the first
      roentgenological examination and transurethral biopsy or resection. The 5-year
      recurrence free rate after transurethral resection of bladder tumor (TUR-BT) of
      the older age group (D group) was lower than that of the other groups. The 5-year
      survival rate of older age group was lower than that of the younger age group.
      However, no statistical significance between the age groups existed concerning
      high grade or high stage tumor and survival after total cystectomy. We clarified
      here that the clinical features of elderly patients who have bladder cancer were
      significantly different from those of younger patients. Otherwise the prognosis
      of patients who have high grade and/or high stage bladder cancer were
      demonstrated to be poor regardless of age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285162
TI  - [Results of combination chemotherapy with etoposide, ifosfamide, peplomycin for
      advanced prostatic cancer].
AB  - Between August, 1986 and August, 1992, 16 combination chemotherapies with
      etoposide (100 mg/body, day 1-5), ifosfamide (50 mg/kg, day 1, 3, 5), peplomycin
      (5 mg/body, day 1-5) were performed on 13 patients with endocrine therapy
      relapsed advanced prostatic cancer. Seven trials were performed on 5 patients who
      received DESP (diethylstilbestrol diphosphate) (500 mg/body, day 1-5) with the
      chemotherapy. In 9 trials performed on 9 patients who did not receive DESP, there
      was no response case. In 7 trials with DESP, one trial had a partial response
      (PR) (14%) and 4 remained objectively stable (stable) (57%). As to adverse
      effects, myelosuppression was observed in all trials but there was no lethal
      toxicity. The one-year survival rate of these patients treated with the
      chemotherapy alone and combined DESP were both about 20%. Therefore we should
      find a more effective treatment for endocrine relapsed prostatic cancer.

PMID- 8285163
TI  - [Clinical results of transrectal hyperthermia in 15 patients with chronic
      abacterial prostatitis].
AB  - A prospective uncontrolled study of the safety and efficacy of transrectal
      hyperthermia was performed on 15 patients with chronic abacterial prostatitis or
      prostatodynia. A total of 6 (1-2 per week) 1-hour sessions of hyperthermia were
      performed. Subjective improvement was fair in 2 cases and slight in 13 cases
      (about 87%). The uroflowmetry and the prostatic size measured by transrectal
      echography did not show any significant changes. The complications were
      epididymitis (1 case), UTI (1 case) and chlamydial urethritis (2 cases). In
      conclusion, this therapy seems to achieve the short-term improvement of chronic
      abacterial prostatitis or prostatodynia.

PMID- 8285164
TI  - [Clinical studies on methicillin-resistant Staphylococcus aureus (MRSA)
      infections].
AB  - We experienced 20 cases of methicillin-resistant Staphylococcus aureus (MRSA)
      infection from April 1991 to September 1992. Of them, 9 showed substantial
      morbidity and their clinical courses are herein reported. The clinical
      presentations of these cases were wound infection and enterocolitis. Although in
      8 cases MRSA was eradicated in 14 to 160 days by effective antibiotics
      administration, one had a fatal outcome. All strains isolated showed similar drug
      sensitivity pattern suggesting hospital infection. Sensitivity to vancomycin and
      arbekacin, however, remained high and these drugs were effective clinically. It
      should be stressed that treatment strategy of MRSA infection should consist of
      isolation of patients with MRSA from other patients, use of disposable equipment
      and products, and serious and continuing concerns of medical personal on
      communicability of MRSA.

PMID- 8285165
TI  - [Fistula between iliac artery aneurysm and ureter: a case report and review of
      the literature].
AB  - We report a patient who developed a fistula between the right ureter and the
      right common iliac artery aneurysm. He had had replacement of a synthetic graft
      for abdominal aortic aneurysm sixteen years previously. The diagnosis was
      confirmed by angiography, retrograde pyelography and computed tomography. The
      fistula was treated by right nephroureterectomy and resection of right common
      iliac artery aneurysm. A brief description of the case is provided and the review
      of the literature is described.

PMID- 8285166
TI  - [Two cases of bladder cancer in patients with chronic renal failure].
AB  - We report here two cases of bladder cancer in patients with chronic renal failure
      who had been treated with hemodialysis. Case 1: A 58-year-old male on
      hemodialysis for 3 years visited with a complaint of gross hematuria.
      Transurethral resection of the bladder tumor (TUR-Bt) was performed and
      histopathological examination showed grade 1, stage pTa transitional cell
      carcinoma (TCC). The patient was followed for 4 years postoperatively without
      recurrence. Case 2: A 64-year-old male with hemodialysis for 1 week was referred
      to our department with a gross hematuria. TUR-Bt was conducted and
      histopathological findings showed grade 2, stage pT1b TCC. In April, 1992, he
      revisited our hospital with bladder tamponade due to massive hematuria, and TUR
      Bt was performed. Histopathologically, the tumors were grade 2, stage pT2 TCC. He
      was followed for 1 year without recurrence.

PMID- 8285167
TI  - [Malignant lymphoma of the prostate--a case report].
AB  - We report a case of prostatic malignant lymphoma causing bilateral
      hydronephrosis. A 73-year-old man was referred to our department, suffering from
      urinary frequency and gross hematuria. The mild elevation of serum prostatic
      tumor markers made us suspect prostatic carcinoma. He was admitted to our
      hospital and needle biopsy of the prostate was performed. Unexpectedly
      histological findings revealed "malignant lymphoma, diffuse large cell type". CT
      scan showed bilateral hydronephrosis, and renal function was decreased. As the
      patient suddenly vomited blood, gastric fiberscopy and biopsy was performed.
      Histological diagnosis of stomach was the same as for the prostate. After
      systemic chemotherapy of cyclophosphamide, adriamycin, vincristine, prednisone
      (CHOP) regimen, renal function improved and the tumor of stomach reduced, but his
      respiratory condition rapidly worsened, and he died about 1 month after
      chemotherapy. Malignant lymphoma involving the prostate is very rare. Especially
      in Japan only 19 cases have been reported including our case. Four of the 19 men
      were in their twenties and so we remind the urologists of the possibility of
      "malignant lymphoma of the prostate" in young patients with dysuria or frequency.

PMID- 8285168
TI  - [Strangulation of the penis by a metallic ring].
AB  - An 81-year-old male patient visited our hospital on November 13, 1992 for the
      treatment of penile edema that had been caused by a metallic ring which he placed
      for fun 4 days prior to the visit. He had placed the metallic ring on the base of
      the penis and subsequent penile edema made it impossible to remove the ring. He
      had no problem with urination. The ring was successfully removed with a metal
      cutting tool. But 3 days later, infected penile ulceration occurred at the base
      of the penis and the necrotic tissue was resected. It took 25 days for the wound
      to heal. It is stressed that penile strangulation is a serious injury and prompt
      removal is necessary.

PMID- 8285169
TI  - [Clinical statistics on outpatients, inpatients and operations at the Department
      of Urology, Yamatokooriyama Social Insurance General Hospital during 12 years
      from 1981 to 1992].

PMID- 8285170
TI  - [Biochemical modulation of chemotherapy of urologic malignancies].
AB  - Generally speaking, the outcome of cancer chemotherapy for urologic malignancies
      is poor. This poor response is attributed to the weak sensitivity to anti-cancer
      agents, represented by renal cell cancer, and the advanced age of most patients
      to tolerate the toxicities of the drugs, as is experienced in prostate cancer
      patients, which leads to insufficient therapy. Biochemical modulation was
      initially used to refer to the enhancement of the effect of 5-FU by modulating
      its pharmacological action by the addition of other drugs. The concept was
      expanded to the enhancement of the effect of the chemotherapeutic agents,
      potentiating the pharmacological action and/or reducing the toxicity, by means of
      any drug or biological modality. This preface is for the following 7 articles
      which were based on the presentations at the Symposium of 42nd Annual Meeting of
      Central Section of Japanese Urological Association in 1992, entitled as
      "Biochemical modulation of chemotherapy of urologic malignancies".

PMID- 8285171
TI  - [Cancer immunotherapy by murine bladder cancer cells transfected with mouse
      interferon-gamma gene].
AB  - We established constitutively an interferon-gamma (IFN-gamma) producing cell line
      (MBT2/gamma) from a mouse bladder cancer cell line (MBT2) by retroviral transfer
      of a mouse IFN-gamma cDNA. Although the in vitro cell growth of these cells was
      unaffected by the IFN-gamma production, their subcutaneous tumor growth in
      syngeneic C3H/He mice was different; MBT2/gamma tumor growth was more strongly
      suppressed (3/20) than that of MBT2 (10/10). MBT2/gamma tumor growth was observed
      in nude mice (6/6). The mice immunized with MBT2/gamma were resistant to tumor
      growth of the parental cells (7/9; 77%), but permitted the growth of another kind
      of C3H/He tumor line. These findings indicate that the reduced tumorigenicity of
      the IFN-gamma producing line was due to the augmented specific antitumor
      immunity, probably as a result of the immunomodulatory effects of the IFN-gamma
      derived from the tumor.

PMID- 8285172
TI  - [The enhancement of the chemotherapeutic effects on human prostate cancer cell-
      the combination with the growth factor interaction inhibitor (suramin)].
AB  - The present study was designed to evaluate the antiproliferative effects of
      suramin and the combination of suramin plus cisplatin (CDDP) on the hormone
      independent human prostate carcinoma cell line (PC-93). In vitro, suramin induced
      a dose-dependent reduction of PC-93 proliferation, and at the clinically
      achievable concentration (300 micrograms/ml), suramin induced a 19.7% decrease in
      proliferation on the 3rd day compared to suramin-free control (P < 0.01).
      However, from the 4th day on the inhibitory action of suramin was reversed
      following exposure. The suramin-cisplatin combination showed an additive effect
      (inhibition ratio 32.4% on the 3rd day), and prolongation of the inhibition
      activity on the 4th day on, but it did not show any synergistic effect. Suramin
      inhibited dose-dependently the growth stimulatory effect of exogenous epidermal
      growth factor (EGF). In vivo study, suramin and suramin-cisplatin combination
      showed antitumor effects continuously in nude mouse implanted PC-93. These
      findings suggest that the inhibitory effects of suramin on PC-93 are mediated by
      inhibition of the EGF-mediated growth mechanism, but by a cytostatic rather than
      cytotoxic manner in vitro. In addition, other mechanisms such as inhibition of
      angiogenesis factor might exist in vivo.

PMID- 8285173
TI  - [Advantages in combination chemotherapy using the camptothecin analogue CPT-11
      and cisplatinum analogues for human testicular cancer xenografts].
AB  - The antitumor effects of combination chemotherapies using CDDP and the
      camptothecin analogue CPT-11 were compared with those of vinca alkaloids or
      podophyllotoxins, and those of CPT-11 and cisplatinum analogues were also
      estimated. Two human testicular cancer xenografts (TTSC -2 and TTSC-3)
      heterotransplanted in nude mice were used. Combination therapy with CPT-11 and
      CDDP resulted in significant tumor regression and was much more effective than
      that of CDDP and vinca alkaloids or podophyllotoxin. The combination of CPT-11
      and either CDDP or 254-S was significantly more effective than that of CPT-11 and
      either carboplatin or DWA2114R. Four evaluable refractory testicular cancers were
      treated with combination chemotherapy with CPT-11 and CDDP or 254-S as third line
      chemotherapy. Two patients remain alive and disease free and two patients died of
      disease. We concluded that the present combination is active in refractory
      testicular cancer.

PMID- 8285174
TI  - [Circumvention of the multidrug-resistance in renal cancer by
      bisbenzylisoquinoline].
AB  - A bisbenzylisoquinoline alkaloid, cepharanthine, significantly enhanced
      vinblastine, adriamycin and etoposide sensitivities in P-glycoprotein positive
      renal cancer cells. However, it did not show any enhancing effect on cisplatin
      sensitivity. Four patients with metastatic renal cell carcinomas were treated
      with intraarterial chemotherapy using vinblastine and/or adriamycin in
      combination with cepharanthine for their metastatic lesions (3 bone and 1
      contralateral kidney metastases). A partial response was observed in 1 patient
      with femoral bone metastasis and a minor response in 1 patient with lumbar bone
      metastasis, although they were also treated with interferons. No adverse effects
      associated with cepharanthine were seen except in one patient complaining of
      redness and burning sense of the skin probably due to its vaso-dilatation effect.

PMID- 8285175
TI  - [The effects of rhodamine 123 on the cell growth of the cultured cells derived
      from urogenital carcinoma].
AB  - Rhodamine 123 (Rh123) is a red fluorescence dye, which is accumulated more and
      retained longer in the mitochondria of malignant transformed cells. In this
      study, the suppressive effects on the growth of cultured urogenital carcinoma
      cells (PC-3 and LNCaP from prostate carcinoma, T-24 from bladder cancer, and SV
      HUC-1 human ureteral transitional cell transformed by SV virus in vitro, ACHN,
      YCR-1 and RCF213 from renal cell carcinoma) were examined. The cell growth of PC
      3, LNCaP, T-24 and SV-HUC-1 was suppressed significantly in a dose dependent
      manner, but that of cells derived from renal cell carcinoma was not suppressed.
      The uptake and elimination of Rh123 in PC-3, ACHN and YCR-1 were not
      significantly different. When administered with verapamil and buthionine
      sulfoximine, which are reported to be chemical modulators of anticancer agents,
      Rh123 suppressed the growth of ACHN and YCR-1 significantly. Rh123 seems to have
      an anticancer effect against the urogenital carcinomas, and the role of Rh123
      with hyperthermia, photodynamic therapy and chemotherapy requires further
      investigation.

PMID- 8285176
TI  - Age-related issues in the treatment of hypertension.
AB  - The highest prevalence of hypertension is now recognized to exist in the elderly
      segment of the population. With the completion of several large-scale studies,
      several of our assumptions regarding elderly hypertensive patients have changed.
      It is now clear that the elderly have shown the greatest benefit from
      antihypertensive therapy. This favorable risk-benefit ratio extends to even the
      very elderly; treatment for hypertension is appropriate for healthy elderly
      individuals, regardless of age. It also extends to elderly individuals who have
      already experienced the consequences of elevated blood pressure. Attitudes toward
      antihypertensive agents have also evolved. Diuretics are appropriate monotherapy
      in many patients, when the dose is kept low. The usefulness of calcium
      antagonists has been confirmed, whereas beta blocker use appears to be indicated
      only in certain subgroups. Recently, angiotensin-converting enzyme inhibitors
      have also been shown to be effective in elderly patients, despite earlier studies
      whose results describe low plasma renin activity in the elderly.

PMID- 8285177
TI  - Systemic hypertension and the renin-angiotensin system in diabetic vascular
      complications.
AB  - Antihypertensive treatment in the diabetic patient is a critical issue because
      hypertension has an impact on all of the vascular complications of diabetes,
      including nephropathy, retinopathy, atherosclerosis, and left ventricular
      hypertrophy. These complications are a consequence of altered endothelial
      vascular smooth muscle interrelations that ultimately enhance vasoconstriction
      and alter the remodeling processes in the vascular wall. Several observations
      suggest that the renin-angiotensin system (RAS) may be an important contributor
      to these processes in diabetes mellitus. In both animal and human studies,
      angiotensin-converting enzyme (ACE) inhibitors have been demonstrated to slow the
      progression of glomerulosclerosis, prevent abnormal remodeling processes in the
      heart following injury, and slow the progression of atherosclerosis. In
      particular, ACE inhibitors appear to protect the kidney more than would be
      expected from simply the lowering of blood pressure and decreasing of
      intraglomerular pressure, possibly because angiotensin II has both hemodynamic
      and direct effects on the glomerulus. Paradoxically, however, the activity of the
      circulating RAS is low in diabetic patients. Part of these seemingly inconsistent
      observations may be due to (1) potential activity of tissue RASs, (2) increased
      sensitivity to angiotensin II in diabetes, or (3) an effect of ACE inhibition on
      other systems in addition to the RAS. Investigation of these mechanisms will be
      important in determining the therapeutic role of inhibition of the RAS in
      diabetes mellitus.

PMID- 8285178
TI  - Fosinopril: an overview.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are an effective, well-tolerated
      option for management of mild-to-moderate hypertension. An increase of nearly
      250% in prescriptions between 1986 and 1990 testifies to the growing importance
      of this drug class. With the development of newer ACE inhibitors, the debate on
      pharmacokinetic and pharmacodynamic differences and the clinical relevance of
      such differences has also been growing in importance. It is in this context that
      the clinical data on fosinopril will be reviewed. Fosinopril has several
      intriguing features, among them a unique chemical structure and elimination
      profile. In addition, preliminary data on cardiac effects and on risk for cough
      are provocative and support further study. The antihypertensive efficacy of
      fosinopril is comparable to other ACE inhibitors. Thus, fosinopril represents an
      interesting and useful addition to this antihypertensive class.

PMID- 8285179
TI  - Angiotensin-converting enzyme inhibitors: more different than alike? Focus on
      cardiac performance.
AB  - Development of an increased systemic vascular resistance and the concomitant
      increase in blood pressure are associated with significant changes in left
      ventricular structure and function. The plasma and tissue renin-angiotensin
      systems play an important, but variable, role in the regulation of blood pressure
      and systemic vascular resistance in normotensive and hypertensive patients. Non
      angiotensin-mediated effects of angiotensin-converting enzyme (ACE) inhibitors
      and/or differential tissue specificities may result in a variable hemodynamic
      response to individual therapies. Using first-pass radionuclide cineangiography,
      the hemodynamic effects of captopril, lisinopril, and fosinopril were compared.
      Fosinopril induced a greater reduction in systemic vascular resistance than did
      equipotent hypotensive doses of captopril or lisinopril and was associated with
      an increase in cardiac output, left ventricular peak ejection rate, and left
      ventricular peak filling rate. Along with previously accumulated data, these
      results suggest that structural differences among ACE inhibitors may result in
      unique physiologic effects. Fosinopril appears to have a cardiotropic effect that
      causes improved left ventricular diastolic performance; this effect is unique
      among currently available ACE inhibitors. The clinical significance of the unique
      profiles of individual ACE inhibitors awaits assessment via comparative clinical
      investigations.

PMID- 8285180
TI  - Controversies in the diagnosis and treatment of hypertension: a personal review
      of JNC V.
AB  - In January 1993 the Joint National Committee on Detection, Evaluation, and
      Treatment of High Blood Pressure published its fifth report (JNC V). The report
      highlighted the importance of systolic hypertension and recommended that
      hypertension should be diagnosed--regardless of age--when systolic blood pressure
      readings are consistently > or = 140 mm Hg. JNC V reflected the opinion in JNC IV
      that several drug classes--including diuretics, beta blockers, angiotensin
      converting enzyme (ACE) inhibitors, calcium antagonists, and alpha blockers--are
      suitable for initiating antihypertensive therapy. However, JNC V gave preference
      to diuretics and beta blockers because these drug classes have been shown to
      reduce the incidence of stroke and cardiovascular events in clinical trials;
      similar studies with the newer drug classes have not yet been completed. This
      recommendation is highly controversial because the benefits of diuretic and beta
      blocker use are most evident in the elderly, and the beneficial effects of these
      drugs on the incidence of coronary events are relatively modest. Further, growing
      experience with ACE inhibitors and calcium antagonists shows that these agents
      lack the metabolic disadvantages of older agents and can exhibit
      antiatherosclerotic and antihypertrophic vasoactivity. Although to date the
      clinical benefits of the newer agents have been documented in conditions other
      than hypertension, the data are persuasive and indicate a probability that these
      drugs will improve prognosis in hypertensive patients. JNC V also emphasized
      lifestyle modifications; however, even when they decrease blood pressure, dietary
      and other nonpharmacologic strategies have not been shown to lower the incidence
      of clinical events.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285181
TI  - Metabolic effects of converting enzyme inhibitors: focus on the reduction of
      cholesterol and lipoprotein(a) by fosinopril.
AB  - It is generally believed that the use of angiotensin-converting enzyme (ACE)
      inhibitors has no effect on the lipid profile. Our recent data show that in
      patients with proteinuric renal disease, serum levels of total cholesterol and
      lipoprotein(a) [Lp(a)] may be lowered during treatment with an ACE inhibitor,
      fosinopril sodium. During a 12-week randomized, placebo-controlled, double-blind
      study involving 26 patients with mild-to-moderate renal impairment, fosinopril
      administration was associated with significant decreases in both urinary protein
      excretion and serum total cholesterol levels, whereas placebo was not. During a 6
      week washout phase, both parameters returned to baseline in fosinopril-treated
      patients and remained unchanged in placebo recipients. In addition, fosinopril
      treated patients had a decrease in plasma levels of Lp(a), whereas this was not
      seen in placebo-treated patients. When data from a subset of 13 patients with
      proteinuric renal disease and hypertension were examined, a significant decrease
      in serum total cholesterol levels was observed; this decrease reversed after
      discontinuation of fosinopril. Analysis of the effect of fosinopril on plasma
      Lp(a) levels in a subset of patients who had type II diabetes mellitus and overt
      proteinuria revealed a significant decrease in plasma Lp(a) after administration
      of fosinopril. Moreover, fosinopril lowered plasma Lp(a) levels in blacks, whose
      pretreatment levels were higher than those of whites with comparable degrees of
      proteinuria and levels of serum total cholesterol. Thus, the reduction in serum
      Lp(a) levels may be related not only to amelioration of proteinuria, but also to
      another direct action of fosinopril on the metabolism of Lp(a).

PMID- 8285182
TI  - Safety update: focus on cough.
AB  - Overall, angiotensin-converting enzyme (ACE) inhibitors have a very low side
      effect profile. However, several reports in the literature cite cough as a
      possible complication of ACE inhibitor therapy. These reports have prompted
      speculation that the risk of cough may differ among ACE inhibitors and that the
      risk may be greater in patients with renal impairment, perhaps because of
      excessive drug accumulation. However, these hypotheses have not been tested in
      prospective, controlled studies. Fosinopril is a long-acting ACE inhibitor with a
      unique chemical structure and an elimination profile that is associated with
      stable clearance, regardless of the degree of renal impairment. Favorable
      clinical experience with fosinopril led to the evaluation of this agent's cough
      profile in a prospective, open-label study. This study focused on the frequency
      of cough in patients with mild-to-moderate hypertension who had previously
      experienced cough while taking another ACE inhibitor. Whereas most prior
      controlled studies and postmarketing surveillance trials measured the frequency
      of cough through spontaneous adverse-event reporting, in this study a methodology
      previously validated in antitussive and mucolytic studies was adapted to provide
      accurate and sensitive measure of fosinopril's cough profile. Twenty-four
      patients were switched from another ACE inhibitor to fosinopril, 10 mg once daily
      for 6 weeks. At study end, the mean occurrence of cough, frequency of cough, and
      cough severity significantly changed from baseline (p < or = 0.0002). Thus,
      fosinopril use was associated with a less frequent, less severe cough in patients
      who experienced cough while taking other ACE inhibitors.

PMID- 8285183
TI  - Renal replacement therapies in the elderly: Part II. Renal transplantation.
AB  - The United States end-stage renal disease (ESRD) population is growing
      progressively older. As a percentage of the overall ESRD population, the number
      of patients 65 years of age and older approached 40% by 1989. However, the
      percentage of ESRD patients with a functioning transplant was only 2.7% in this
      age group. Success of transplantation in geriatric ESRD patients over the last
      decade is due to improved patient selection as well as the use of cyclosporine A
      and lower doses of corticosteroids, with the achievement of 1-year patient and
      graft survival rates of 85% and 75%, respectively. For patients older than 60 or
      65 years, the 5-year "functional" graft survival is 55% to 60%. Although overall
      results are excellent, the management of transplantation in the elderly requires
      an understanding of pharmacology, immunology, and physiology peculiar to this age
      group. Since the elderly have a degree of immune incompetence, they require less
      aggressive immunotherapy. Elderly patients have decreased hepatic enzyme
      activity, especially the P450 system, and therefore require a lower cyclosporine
      dose. Although elderly patients experience less rejection episodes than younger
      patients, graft loss in the elderly transplant recipient is due mainly to patient
      death. Most common causes of death in the elderly transplant recipient are
      cardiovascular disease and infection related to peaks of immunosuppression.
      Shortage of cadaver kidneys and limited life expectancy of the geriatric ESRD
      patient make allocation of cadaver kidneys to patients over 70 years (and even 65
      years) a controversial issue and an ethical dilemma. Use of elderly cadaver
      donors (over 55 to 60 years) is associated with inferior success rates and is not
      an optimal solution to shortage of cadaver kidneys.

PMID- 8285184
TI  - Angiotensin-converting enzyme inhibition partially prevents diabetic
      organomegaly.
AB  - The present study was conducted to evaluate whether captopril prevents the
      organomegaly and accumulation of matrix proteins that normally accompanies the
      diabetic state. The following groups of rats were studied: normal rats, normal
      rats treated with captopril (30 mg/kg/d orally), streptozotocin diabetic rats,
      and diabetic rats treated with captopril. All rats were killed at 10 weeks for
      histologic and morphometric evaluation of tissues. Compared with the normal rats,
      the diabetic rats demonstrated significant hepatomegaly, nephromegaly, and
      cardiomegaly, and the increase in organ size was directly related to increasing
      levels of protein glycosylation. The development of organomegaly was partially
      prevented by captopril. We determined by morphometry that the hepatomegaly seen
      in the diabetic rats was due to an increase in cell size and number, while the
      nephromegaly seen in the diabetic rats was due to an increase in tubular and
      glomerular cell size and is associated with glomerular hypertrophy. Captopril
      prevented the development of hepatic and renal cell hypertrophy and glomerular
      hypertrophy. These effects of captopril were not associated with detectable
      changes in body weight or levels of glucose, protein glycosylation, glycosuria,
      or renal histologic changes secondary to glycosuria. The diabetic rats
      demonstrated significant glomerular mesangial matrix expansion, and captopril
      treatment partially prevented that expansion. In conclusion, captopril prevents,
      in part, the development of organomegaly in diabetic rats, and this effect is due
      mainly to the prevention of the development of cellular hypertrophy. The present
      findings are most consistent with a direct effect of captopril on cell metabolism
      during diabetes mellitus.

PMID- 8285185
TI  - Aminoglycoside-induced Fanconi's syndrome.
AB  - Nephrotoxicity manifested by renal insufficiency is a well-known consequence of
      aminoglycoside administration in hospitalized patients. We report two cases of
      aminoglycoside-induced nephrotoxicity as manifested by proximal tubular
      dysfunction (Fanconi's syndrome). In the two patients reported, the tubular
      dysfunction occurred at the extremes of renal function. In both patients, tubular
      function returned to normal when the antibiotic was discontinued. Because of the
      widespread use of these antibiotics in the critically ill patient, it may be
      prudent to recognize this disorder when managing fluids, electrolytes, and
      nutrition.

PMID- 8285186
TI  - Reversible renal failure in an elderly woman with renal artery stenosis.
AB  - Renal artery stenosis not only causes severe hypertension, but if left untreated,
      can progress to renal failure. A 64-year-old woman with a serum creatinine of 1.8
      mg/dL and mild proteinuria developed progressively severe hypertension that was
      resistant to a calcium channel blocker. The patient received lisinopril, which
      was discontinued after 2 days because of nonspecific symptoms. One week later, an
      intravenous pyelogram showed a normal-sized but poorly functioning left kidney
      and a nonfunctional right kidney. The serum creatinine increased to 11.7 mg/dL
      and the patient was begun on hemodialysis. A renal arteriogram performed 6 weeks
      later for persistent hypertension showed bilateral renal artery occlusion; renal
      vein renin values from the left kidney were higher than those from the right
      kidney. After 11 weeks of hemodialysis, thrombolytic therapy followed by
      angioplasty was performed. Three weeks later, the renal function had returned to
      baseline (serum creatinine of 1.8 mg/dL) and hypertension was controlled with a
      beta-blocker. Renal artery stenosis is a potentially reversible cause of renal
      failure and should be considered in the evaluation of elderly patients with
      hypertension, even in the presence of renal failure.

PMID- 8285187
TI  - Bilateral vocal cord paralysis secondary to treatment of severe hypophosphatemia
      in a continuous ambulatory peritoneal dialysis patient.
AB  - Neuromuscular complications, including tetany and laryngeal spasm, are recognized
      complications of hypocalcemia and hypomagnesemia. We present a continuous
      ambulatory peritoneal dialysis patient with hypomagnesemia who developed
      hyperphosphatemia and profound hypocalcemia after oral phosphate replacement for
      severe hypophosphatemia. The combination of hypocalcemia and hypomagnesemia
      resulted in life-threatening bilateral vocal cord paralysis. Phosphate
      replacement should be determined and given cautiously, particularly in patients
      with renal failure and concomitant electrolyte disturbances.

PMID- 8285188
TI  - Simultaneous development of diffuse immunoblastic lymphoma in recipients of renal
      transplants from a single cadaver donor: transmission of Epstein-Barr virus and
      triggering by OKT3.
AB  - Rapidly progressive diffuse immunoblastic lymphoma is an uncommon but devastating
      complication of organ transplantation that typically occurs early in the
      postoperative period. The fulminant course is characterized by progressive
      encephalopathy and coagulopathy, with malignant B-cell infiltration in the graft
      and other sites. Both de novo infection with Epstein-Barr virus (EBV) and
      treatment with the monoclonal antibody OKT3 have been implicated in the
      development of this disorder. We report two patients who received renal
      transplants from the same cadaver donor, with transmission of EBV from the same
      source, in whom treatment with OKT3 for acute rejection triggered the
      simultaneous development of fulminant and fatal B-cell immunoblastic lymphoma. We
      suggest that antilymphocyte agents be used with caution in EBV-seronegative graft
      recipients who receive a transplant from an EBV-seropositive donor to minimize
      the risk of this lethal complication.

PMID- 8285189
TI  - Metabolic acidosis following jejunoileal bypass.

PMID- 8285190
TI  - Monoclonal antibodies in organ transplantation.

PMID- 8285191
TI  - An adult with the nephrotic syndrome unresponsive to treatment.

PMID- 8285192
TI  - Race, socioeconomic status, and the development of end-stage renal disease.
AB  - The reasons for the increased annual incidence of end-stage renal disease (ESRD)
      in blacks compared with whites are unclear, but may include lack of access to
      treatment of the causative disease, which likely relates closely to socioeconomic
      status (SES). End-stage renal disease rates for diabetic glomerulosclerosis,
      hypertensive nephrosclerosis, and glomerulonephritis were determined in the 9,390
      black and white New York State residents who began treatment within the Medicare
      program between 1982 and 1988. The relationship between the incidence of ESRD,
      age, and SES, as measured by the race-specific median family income in the
      patient's zip code, was estimated using a series of logistic-regression models
      for 12 populations: three causes of renal failure by two races by two sexes. For
      whites, incidence rates of diabetic glomerulosclerosis and hypertensive
      nephrosclerosis were significantly negatively associated with declining SES for
      the 45 to 65 year and 25 to 55 year age groups, respectively. In contrast, there
      was no relationship between the incidence of these diseases and SES in blacks.
      For glomerulonephritis, effects of SES were minor for both races. Better access
      to treatment of diabetes and hypertension might well decrease the annual
      incidence of ESRD due to diabetic glomerulosclerosis and hypertensive
      nephrosclerosis in whites. If the SES measures used for blacks are adequate,
      predisposition to progressive renal damage in response to renal injury or
      environmental factors other than SES are stronger risk factors for ESRD than SES.

PMID- 8285193
TI  - Altered clearance of N-1 methylnicotinamide associated with the use of low doses
      of cyclosporine.
AB  - To improve the monitoring of patients on low doses of cyclosporine there is a
      need for new tests of tubular function. N-1 methylnicotinamide (NMM) is an
      endogenous organic cation that is secreted by the proximal tubule and its
      clearance can be measured. In 27 patients with psoriasis, serial measurements of
      NMN clearance, plasma aldosterone, plasma chloride, bicarbonate, and magnesium
      were compared with changes in the radionuclide measurement of glomerular
      filtration rate and renal blood flow before, during, and after a 3-month course
      of low-dose cyclosporine (< 5 mg/kg/d). N-1 methylnicotinamide clearance
      decreased significantly with cyclosporine only (2.5 mg/kg/d, n = 10, P < 0.01).
      Recovery of NMN clearance lagged behind that of glomerular filtration rate and
      renal blood flow. Serum magnesium decreased significantly on cyclosporine (2.5
      mg/kg, n = 10, P < 0.01; 5 mg/kg, n = 9, P < 0.0001). In the whole group, plasma
      potassium increased significantly (n = 27, P < 0.02) and plasma aldosterone was
      inappropriately low. Low doses of cyclosporine in psoriasis cause a reduced
      clearance of NMN, hypomagnesemia, and a variable hyperchloremic acidosis.
      Nifedipine may alter these biochemical variables without necessarily improving
      renal hemodynamics. The delayed recovery of NMN clearance in comparison with
      renal haemodynamic measurements following cyclosporine therapy suggests that this
      noninvasive test of tubular function may be a marker of persisting cyclosporine
      nephrotoxicity and that it should be evaluated further.

PMID- 8285194
TI  - Renal biopsy in infants and children.
AB  - Renal biopsy is a technically difficult procedure in children. Some centers are
      still using general anesthesia, fluoroscopy, and/or open renal biopsies in young
      infants. We evaluated the safety and efficacy of two different types of 18-gauge,
      automated, spring-loaded disposable biopsy needles in 43 children, aged 8 months
      to 16 years, under ultrasound guidance. Microinvasive ASAP18 (Boston Scientific
      Corp, Watertown, MA) needles retrieve 19-mm long specimens only, while Ultra-Cut
      needles (Medical Device Technologies, Inc, Gainesville, FL) are adjustable and
      can retrieve 6-, 13-, or 19-mm specimens. Technically, Ultra-Cut needles are
      easier to use in infants or when small kidneys are biopsied. While two infants
      required intravenous ketamine, the remaining biopsies were done with intravenous
      sedation. Ultrasound-guided renal biopsy with 18-gauge microinvasive needles and
      intravenous sedation is a safe and reliable method for obtaining biopsy specimens
      in older children, as well as in small infants.

PMID- 8285195
TI  - A nomogram approach to hemodialysis urea modeling.
AB  - Two sets of nomograms were developed for modeling hemodialysis urea kinetics. The
      first set is designed to arrive at an initial dialysis prescription. One nomogram
      estimates the mass transfer area coefficient (KoA) based on urea clearances of a
      dialyzer, based on urea clearances provided in the manufacturer's product
      literature. A second nomogram uses the dialyzer KoA value to estimate the
      expected in vivo urea clearance (K) based on the nominal blood flow rate. The
      computations include corrections for blood flow-related errors in urea clearance,
      blood water content, and cardiopulmonary recirculation. Mean urea clearance
      measured in a series of patients was 226 +/- 22 mL/min and did not differ
      significantly from mean clearance estimated using this nomogram (232 +/- 8
      mL/min). Another pair of nomograms, based on an anthropometric formula, can be
      used to estimate urea distribution volume (V) from patient sex, height, and
      weight. The first set of nomograms is designed to estimate an initial dialysis
      prescription because the nomograms propose an estimated K and an estimated V.
      Once the target Kt/V is chosen, the appropriate initial treatment time (t) is
      computed algebraically. The second set of nomograms was developed to verify
      delivery of the dialysis prescription and to estimate the normalized protein
      catabolic rate (PCRn). Kt/V is estimated from the postdialysis to predialysis
      blood urea nitrogen ratio and the ratio of ultrafiltrate volume to postdialysis
      weight (UF/W). The PCRn is estimated from the predialysis blood urea nitrogen and
      Kt/V. In a series of 115 patients, Kt/V and PCRn determined from the nomograms
      correlated highly with corresponding values determined from formal urea modeling
      (r = 0.99).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285196
TI  - Cuprophane but not synthetic membrane induces increases in serum tumor necrosis
      factor-alpha levels during hemodialysis.
AB  - Cytokine synthesis and secretion by blood mononuclear cells is a well-documented
      phenomenon in hemodialyzed patients. The present study was conducted in 17
      chronically hemodialyzed patients to test the relative effect of uremic toxicity,
      membrane biocompatibility, dialysate composition, and the risk of endotoxinemia
      on the serum level of tumor necrosis factor-alpha (TNF-alpha). The only
      significant parameter that influenced circulating TNF-alpha was the chemical
      characteristics of the dialyzer membrane. Tumor necrosis factor-alpha levels
      significantly increased during the session with cuprophane, whereas they
      decreased with AN69. The TNF-alpha increase was documented whatever the dialysate
      buffer and the presence or absence (negative Limulus amoebocyte lysate test) of
      endotoxin in the dialysate. In the subgroup of patients treated with a
      contaminated dialysate and AN69, none had clinical symptoms and the central body
      temperature remained constant throughout the session. In these patients, serum
      TNF-alpha levels did not change after priming the dialyzer with sterile saline.
      In conclusion, the serum TNF-alpha level during hemodialysis appears to be
      modulated by biocompatibility, permeability, and binding properties of dialysis
      membrane rather than dialysate composition. Endotoxin in the dialysate did not
      result in positive TNF-alpha balance no matter what its possible priming effect
      on mononucleated blood cells.

PMID- 8285197
TI  - Heterogeneity in gentamicin clearance between high-efficiency hemodialyzers.
AB  - Gentamicin is frequently prescribed for treatment of gram-negative infections in
      patients on dialysis. The amino-glycoside is renally excreted; therefore, dosage
      modifications are required in patients on hemodialysis. The introduction of short
      duration dialysis using high-efficiency hemodialyzers requires that the
      dialysance of gentamicin be re-examined. We recently demonstrated that high
      efficiency dialyzers have a superior gentamicin clearance as compared with
      conventional dialyzers. In this study we examined the dialysance of gentamicin in
      two high-efficiency dialyzers using a randomized, controlled, cross-over design.
      Despite a comparable amount of dialysis (Kt/V urea), rate of dialysis (K/V urea),
      and ultrafiltration, there were significant differences noted in gentamicin
      removal between the high-efficiency cuprammonium rayon and polysulfone dialyzers.
      Furthermore, the amount of dialysis (Kt/V urea) could predict the fractional
      gentamicin clearance for the TAF 175L dialyzer (Terumo Corp, Somerset, NJ) and
      may be useful in the initial planning of gentamicin therapy. In addition, since
      gentamicin is a middle molecule (molecular weight, 500 to 2,000 d), the study
      suggests a superior middle molecule clearance of cuprammonium rayon dialyzer
      compared with a high-efficiency polysulfone dialyzer. The substantial
      heterogeneity in gentamicin clearance, even between dialyzers of the same class,
      emphasizes the importance of monitoring drug levels in hemodialysis patients
      receiving this drug.

PMID- 8285198
TI  - Influence of erythropoietin on dialyzer reuse, heparin need, and urea kinetics in
      maintenance hemodialysis patients.
AB  - The administration of erythropoietin (EPO) in maintenance hemodialysis may affect
      urea kinetic parameters by altering dialyzer function during first use and reuse,
      and dietary protein intake as a consequence of increased appetite. In the present
      study, the effect of EPO treatment on urea kinetic parameters in case of reuse (n
      = 14) and first use (n = 10) of dialyzers was assessed in 24 clinically stable
      hemodialysis patients who were evaluated before and during EPO treatment. In
      addition, the heparin need and the number of uses before discarding the dialyzer
      were registered. No significant differences between urea kinetic parameters
      before compared with during EPO treatment were noted in the overall population or
      in the subgroups treated with reused or first-use dialyzers. However, in 13
      patients with a low baseline protein catabolic rate (pcr(wt)) (pcr(wt) < 1.0
      g/kg/24 hr before EPO treatment), pcr(wt) increased from 0.81 +/- 0.04 to 0.93 +/
      0.06 (+ 15%, P < 0.01). The heparin dosage increased from 6,693 +/- 419
      IU/session to 7,659 +/- 566 IU/session and from 5,538 +/- 594 IU/session to 6,918
      +/- 649 IU/session (P < 0.05) in the subgroups treated with reused or first-use
      dialyzers, respectively. Nevertheless, when dialyzer reprocessing was performed,
      the number of achieved uses before discarding the dialyzers was reduced after the
      introduction of EPO (5.4 +/- 0.4 v 3.4 +/- 0.4, P < 0.01). In conclusion, during
      EPO treatment urea kinetic parameters were not affected in case of dialyzer first
      use or in case of reuse. In patients with low pretreatment values, pcr(wt)
      increased, possibly indicating improved protein intake in malnourished
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285199
TI  - Frequency and outcome of pregnancy in women on dialysis.
AB  - Two hundred six dialysis units were surveyed to determine the frequency and
      outcome of pregnancy in dialysis patients. Ninety-four percent of the units
      responded. Of the 1,281 women of childbearing age cared for in these units, 1.5%
      became pregnant during the 2-year study period. Thirty-seven percent of
      pregnancies resulted in surviving infants. Pregnancies that took place from 1990
      on had a 52% success rate. There was no significant difference in outcome as a
      result of dialysis modality or erythropoietin use. All but one of the infants
      were premature. Pregnancy entailed substantial risks for the mother.

PMID- 8285201
TI  - Comparison of different measurements of lean body mass in normal individuals and
      in chronic peritoneal dialysis patients.
AB  - To evaluate different methods of measuring lean body mass (LBM) in chronic
      peritoneal dialysis (CPD) patients, we first made comparisons in seven normal
      subjects. Seven methods (total body potassium [TBK] counting, bioelectrical
      impedance with calculations according to Segal and Deurenberg, near-infrared
      interactance with and without exercise level included as a variable,
      anthropometric measurements, and creatinine kinetics) were compared with the
      standard method of underwater weighing (UW) for measuring LBM. Significant
      correlations with LBM measured by UW (r > 0.938) were found with LBM measured by
      all other methods. Compared with UW, the best result in normals was found with
      TBK as it had high r values, small y-intercepts, and slopes of regression lines
      close to unity in both measurements of LBM and %LBM; in addition, fat-free mass
      index by TBK best approximated that by UW and TBK had the lowest mean prediction
      error with UW. In 11 patients on CPD, LBM was measured by all the above methods
      except UW. Significant correlations of all methods with LBM measured by TBK used
      as the reference standard were noted (all r > 0.76) in the CPD population. The
      LBM measured by creatinine kinetics correlated best (by kilograms or percentage
      of body weight [%BW]) with LBM from TBK compared with the other methods in which
      values tended to be higher. The fat-free mass index by creatinine output was
      nearest to the fat-free mass index by TBK. The root mean square prediction error
      was lowest between LBM by creatinine output and that by TBK. The findings support
      the concept of measuring creatinine outputs in CPD patients for estimates of LBM
      as an index of nutritional status as well as for creatinine clearances as an
      index of adequacy. Total body potassium and creatinine output measurements of LBM
      reflect the LBM at normal body fluid volumes ("dry weight") and may be better
      indices of nutrition in dialysis patients than the other techniques, which
      include excess fluid in the LBM.

PMID- 8285200
TI  - Functional longevity of the human peritoneum: how long is continuous peritoneal
      dialysis possible? Results of a prospective medium long-term study.
AB  - Long-term peritoneal dialysis requires the maintenance of the transport function
      of the peritoneal membrane, and appropriate studies of possible changes are
      necessary. The quantification of peritoneal mass transfer coefficients (MTCs) has
      been judged to be the ideal method for the evaluation of peritoneal diffusion.
      The aim of the present study was to show the results of the prospective
      evaluations in long-term continuous ambulatory peritoneal dialysis patients. We
      have studied the clinical incidents and peritoneal function of 56 patients who
      started continuous ambulatory peritoneal dialysis between 1980 and 1988, and have
      completed at least 3 years of follow-up. Ultrafiltration capacity was calculated
      with a standardized formula. All patients were studied for peritoneal diffusion
      of urea and creatinine at least once a year. The evaluation consisted of a
      kinetic study done by means of a peritoneal equilibration curve for urea and
      creatinine, applying a bicompartmental mathematical model to calculate the MTCs.
      The sequential mean values for urea-MTC did not show significant changes over the
      observation period (20.7 +/- 5.9 mL/min for the first year v 19.8 +/- 6 mL/min
      for the fifth year). Creatinine-MTC values showed a significant increase over
      this period in the paired data analysis. The decrease of the urea-MTC to
      creatinine-MTC ratio may be an early and appropriate index for measuring these
      changes when the individual values are in the normal range. On the other hand,
      peritoneal ultrafiltration capacity significantly decreased over this period
      (1,800 +/- 530 mL/d v 1,400 +/- 600 mL/d, P < 0.01). The high rate of accumulated
      days of peritoneal inflammation was related to these significant changes, and
      thus may be proposed to be a good prognostic index of long-term peritoneal
      survival. These long-term functional changes might be related to the effect of
      injuries on the preservation of the normal peritoneal structure. We conclude that
      after 5 to 11 years, the human peritoneum shows functional stability (diffusion
      and water transport) in patients with low rates of peritoneal inflammation. With
      a few exceptions, represented by patients with a high rate of peritoneal
      inflammation, long-term peritoneal dialysis accomplished its newly entrusted
      task.

PMID- 8285202
TI  - 1% amino acid peritoneal dialysate: single-cycle study in diabetic patients with
      end-stage renal disease.
AB  - Uremia is associated with multiple abnormalities of carbohydrate and protein
      metabolism, which are partially corrected by continuous ambulatory peritoneal
      dialysis with dextrose-based solutions. The hormonal and metabolic effects of
      amino acid (AA)-based peritoneal dialysis have been studied in nondiabetic uremic
      patients. Such solutions may be particularly suitable for diabetic patients with
      end-stage renal disease provided the safety and efficacy of such solutions can be
      established. We have studied and compared the metabolic and hormonal responses to
      a single-cycle exchange of dextrose versus a 1% AA-based continuous ambulatory
      peritoneal dialysis solution in six diabetic patients with end-stage renal
      disease. In the fasting state and under similar free insulin concentrations, use
      of the AA solution led to a higher mean glucose concentration (109 +/- 16 mg/dL
      with dextrose solution v 128 +/- 25 mg/dL with AA solution, P < 0.05). Levels of
      alanine, lactate, pyruvate, glycerol, non-esterified fatty acids, and
      triglycerides were similar with the use of either solution. Use of the AA-based
      solution led to increases in the mean values of the branched chain AAs for the
      period of the study (valine 131 +/- 10 mumol/L with dextrose solution v 331 +/-
      40 mumol/L with AA solution, P < 0.01; leucine 72 +/- 7 mumol/L with dextrose
      solution v 129 +/- 11 mumol/L with AA solution, P < 0.01; isoleucine 48 +/- 5
      mumol/L with dextrose solution v 103 +/- 11 mumol/L with AA solution, P <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285203
TI  - Predictors of survival in continuous ambulatory peritoneal dialysis patients: the
      importance of prealbumin and other nutritional and metabolic markers.
AB  - Serum markers of visceral and somatic protein status are directly correlated with
      the survival of hemodialysis patients. We prospectively examined the relationship
      of single baseline levels of serum albumin, cholesterol, creatinine, and urea to
      prognosis in 80 continuous ambulatory peritoneal dialysis patients monitored for
      up to 33 months. Other variables tested included age, race, gender, diabetes,
      cause of end-stage renal disease, and number of months on dialysis. The Cox
      proportional hazards model was used to determine independent predictors of
      mortality risk. In a subgroup of 33 patients followed for up to 21 months, the
      predictive value of single measurements of baseline serum prealbumin also was
      tested. Overall, 29 patients died during the study. Independent predictors of
      mortality risk included serum albumin (P = 0.024) and creatinine (P = 0.006),
      diabetes (P < 0.06), prior months on dialysis (P < 0.05), and older age (P =
      0.18). In a subgroup of 33 patients with prealbumin measurements, there were nine
      deaths over 21 months. A serum prealbumin level less than 30 mg/dL was associated
      with an increased mortality rate compared with higher prealbumin values (odds
      ratio, 3.8; P = 0.09). We conclude that markers of visceral and somatic nutrition
      are important and independent predictors of mortality risk in continuous
      ambulatory peritoneal dialysis patients. We are unable to suggest whether the
      relationship is causal or causative. However, the predictive value of these
      single baseline markers were valid for up to 33 months. We also note that
      patients with diabetes are at an increased risk even after adjusting for somatic
      and visceral protein status.

PMID- 8285205
TI  - Nationally speaking. Value in a changing environment.

PMID- 8285204
TI  - Results of ultrasound-assisted diagnosis of tunnel infections in continuous
      ambulatory peritoneal dialysis.
AB  - The management of catheter-related infections has become a major challenge in
      continuous ambulatory peritoneal dialysis treatment. Early recognition and
      discrimination of mere exit site infections from more invasive and catheter
      menacing tunnel infections (TIs) are of therapeutic importance. As the diagnosis
      of TI is still based on clinical signs and only indicates advanced infections, we
      studied the usefulness of the ultrasound examination (UE) of the continuous
      ambulatory peritoneal dialysis catheter. Examinations were made by a mobile
      ultrasound unit using a 7.5 MHz transducer. Sixty-two continuous ambulatory
      peritoneal dialysis patients with an Oreopoulos Zellermann catheter (Oreopoulos
      Zellerman Cathete-THWII, Baxter GmbH, Unterschleissheim, Germany) were studied
      repeatedly between February 1991 and July 1992. Pericatheter fluid collection
      (with typical sonographic localization) was consistent with surgical findings and
      histopathologic examination and proved to be a reliable criterion of TIs. The
      incidence of TIs was significantly higher when using UE (0.35/patient-year)
      compared with the usual clinical criteria (0.12/patient-year, P < 0.01).
      Staphylococcus aureus exit site infections were predominant and had the highest
      risk of concomitant TIs (83%). Eleven of 25 patients with a positive UE lost
      their catheter due to infectious complications, while no patient with a negative
      UE underwent operation for infectious reasons (P < 0.01). The peritonitis rate
      (0.64/patient-year) was markedly increased when UE indicated a TI (1.7/patient
      year, P < 0.01). We conclude that sonography is a sensitive tool for the early
      diagnosis of unsuspected TIs. Sonography is a bedside method used for screening
      purposes and allows us to control the treatment regimen.

PMID- 8285206
TI  - Occupation embedded in a real life: interweaving occupational science and
      occupational therapy. 1993 Eleanor Clarke Slagle Lecture.
AB  - This lecture presents an example of research in the genre of interpretive
      occupational science and demonstrates how occupational science can inform
      clinical practice. The innovative qualitative methodology used blended elements
      of the anthropological tradition of life history ethnography, ethnomethodology,
      the naturalistic methods used by Mattingly and Schon to study practice, and
      especially narrative analysis as described by Polkinghorne. The bulk of the paper
      is presented in the form of a narrative analysis that provides an account of a
      stroke survivor's personal struggle for recovery, a story that emerged from
      transcription, coding, and analysis of transcripts from approximately 20 hours of
      interview time. First, this narrative analysis provides an example of how the
      occupational science framework can evoke a particular kind of storytelling in
      which childhood occupation can be related to adult character. Storytelling of
      this kind is later shown to be therapeutic for the stroke survivor. Next, the
      narrative illustrates how rehabilitation can be experienced by the survivor as a
      rite of passage in which a person is moved to disability status and then
      abandoned. Finally, a picture is given of how occupational story making and
      occupational storytelling embedded in real life can nurture the human spirit to
      act and can become the core of clinical practice.

PMID- 8285207
TI  - Short-term regulation of renal Na-K-ATPase activity: physiological relevance and
      cellular mechanisms.
AB  - Sodium-potassium-activated adenosinetriphosphatase (Na-K-ATPase; the Na:K pump),
      located at the basolateral domain of epithelial cells, provides the driving force
      for active sodium and potassium translocation and for the secondary active
      transport of other solutes across the renal tubules. Short-term regulation of
      renal Na-K-ATPase activity (i.e., not reflecting changes in its biosynthesis
      rate) provides an important mechanism of modulating tubule transport and thus the
      final Na and K urinary excretion. Recent studies have provided abundant evidence
      that such regulation is effected by complex functional networks that are specific
      for different nephron segments and involve distinct and often mutually
      interacting intracellular signal transduction pathways. The effects of hormones
      and autacoids linked to alterations in cell adenosine 3',5'-cyclic monophosphate
      and consequently of protein kinase A, in the levels and distribution of protein
      kinase C, or in the generation of various eicosanoids provide examples of rapid
      Na:K pump activity modulation by the mechanisms mentioned above. In this review
      we assess the roles of specific intracellular messengers and the manner in which
      they, and especially protein kinases, might interact with the pump in the short
      term regulation of its activity; also, we examine the emerging evidence
      supporting the participation of the cytoskeleton in this process.

PMID- 8285208
TI  - Phosphonoformic acid blunts adaptive response of renal and intestinal Pi
      transport.
AB  - Parenteral administration of phosphonoformic acid (PFA) results in phosphaturia,
      but the effects of oral PFA on Pi handling are not known. To assess this effect,
      PFA was administered in drinking water for 5 days to rats stabilized on normal
      (NPD) or low (LPD) phosphorus diets. In renal brush-border membrane vesicles
      (BBMV), kinetic studies showed a higher apparent Vmax for Pi in rats on LPD
      compared with rats on NPD (1,840 +/- 274 vs. 1,111 +/- 192 pmol.mg-1.5 s-1,
      respectively, P < 0.05, n = 5). In LPD rats, PFA reduced the apparent Vmax for Pi
      to 1,047 +/- 191 pmol.mg-1.5 s-1 (P < 0.05, n = 5) with no change in the apparent
      Km. Similarly, there was a higher apparent Vmax for Pi in intestinal BBMV from
      rats on LPD compared with rats on NPD. In LPD rats, PFA reduced the apparent Vmax
      for Pi with no change in the apparent Km. Oral PFA had no effect on the kinetics
      of Pi transport in renal or intestinal BBMV from rats on NPD. Pi-protectable
      [14C]PFA binding was lower in renal BBMV from PFA-treated LPD rats, but membrane
      fluidity was not different. Orally administered PFA can blunt the adaptive
      response of the renal and intestinal BBM to an LPD. The downregulation of Na(+)
      Pi cotransport is mediated through a reduction in the number of Na(+)-Pi
      cotransporters.

PMID- 8285209
TI  - Carbonic anhydrase II mRNA is induced in rabbit kidney cortex during chronic
      metabolic acidosis.
AB  - Carbonic anhydrase II (CA II), the predominant isoform of carbonic anhydrase in
      the kidney, is believed to be localized primarily in the cytoplasm of proximal
      tubule and collecting duct intercalated cells. Carbonic anhydrase facilitates H+
      secretion by catalyzing the formation of HCO3- from OH- in the presence of CO2.
      We have shown that renal cortical CA II activity is stimulated during 4-6 days of
      chronic metabolic acidosis [L.P. Brion, B.J. Zavilowitz, O. Rosen, and G.J.
      Schwartz. Am. J. Physiol. 261 (Regulatory Integrative Comp. Physiol. 30): R1204
      R1213, 1991]. The purpose of these studies was to examine under similar
      conditions the regulation of CA II mRNA. We obtained a major portion of the
      rabbit CA II cDNA by reverse transcription of total RNA from rabbit kidney
      followed by amplification using oligonucleotide primers prepared from conserved
      areas in the coding regions of human, mouse, and chick CA II cDNAs in a
      polymerase chain reaction (RT-PCR). The 696-bp RT-PCR product was sequenced and
      found to be 71-86% homologous to CA II cDNAs from the other three species. The
      deduced amino acid sequence agreed closely (> 97%) with a previous Edman analysis
      of rabbit erythrocyte CA II. Northern analysis showed expression of a
      approximately 1.4 kb RNA, with cortex > outer medulla > inner medulla. Steady
      state mRNA expression from kidney cortex of acid-treated rabbits was about twice
      that from controls, when normalized to the expression of beta-actin or malate
      dehydrogenase. The stimulation of CA II mRNA was greater after 3 days than after
      5-6 days of acid treatment. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285210
TI  - Regulation of cell pH by K+/H+ antiport in renal epithelial cells.
AB  - Acid-loaded opossum kidney (OK) cells secrete H+ by Na+/H+ exchange and by a
      Na(+)- and HCO3(-)-independent pathway that has not been fully characterized. We
      studied the Na(+)-independent component by measuring H+ flux using the pH
      sensitive trapped indicator 2',7'-bis(2-carboxyethyl)-5(6)- carboxyfluorescein.
      Two Na(+)-independent H(+)-transport systems were identified in acid-loaded cells
      perfused with HCO3(-)-free buffers. The minor component appears to be a
      conductive pathway for H+, over 90% inhibitable by 5 mM barium. The major
      component is stimulated by extracellular K+ and was fully active in the presence
      of barium, amiloride, ouabain, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid,
      and bumetanide and in the absence of Cl-. Ammonium inhibited the H+ flux by 72%
      at 50 mM, and the H+ flux could be accelerated two- to threefold by limited
      proteolysis of intact cells using kallikrein or papain. In cells pretreated with
      barium, the K(+)-induced H+ flux caused no change of bis-oxonol fluorescence,
      suggesting an electroneutral pathway. The H+ flux was a saturable function of
      extracellular K+ (Michaelis constant 55 mM), and flux reversed when the K+
      gradient was reversed. Similarly, the H+ flux was a linear function of the H+
      gradient and reversed when the H+ gradient reversed. Evidence for ongoing K(+)
      induced H+ flux was also found in nonacidified cells. First, changing perfusate
      K+ from 5 to 50 mM alkalinized baseline cell pH, an effect not reproduced by
      barium despite an equivalent depolarizing effect. Second, increasing perfusate K+
      from 5 to 50 mM completely eliminated the acidification produced by 1 mM
      amiloride. We conclude that the OK cell expresses two Na(+)-independent acid-base
      transport systems. One is a barium-sensitive electrogenic H+ conductance and the
      other functions as an electroneutral K+/H+ antiporter. The antiporter is capable
      of H+ extrusion from acid-loaded cells but in normal cells functions in the
      reverse direction, as an H+ loader. The K+/H+ antiporter appears to be one of the
      major systems regulation cell pH in these cells, balancing the H+ efflux mediated
      by Na+/H+ exchange.

PMID- 8285211
TI  - Citrate and calcium effects on Tamm-Horsfall glycoprotein as a modifier of
      calcium oxalate crystal aggregation.
AB  - We measured the effects of Tamm-Horsfall glycoprotein (THP) on calcium oxalate
      monohydrate (COM) crystal aggregation (Ac) in vitro as well as intrinsic
      viscosities (Vi) of THP at pH 5.7 and 200 mM NaCl and studied the effects of
      calcium and citrate on these parameters. THP were isolated from 24-h urines of
      seven male recurrent calcium stone formers (RCSF) and eight age-matched male
      healthy volunteers (N, normal). At basal conditions, RCSF-THP inhibited Ac by 28
      +/- 10% and normal THP by 60 +/- 6% (P = 0.028). In the presence of calcium,
      increasing THP concentrations from 16 to 28 and 40 mg/l progressively lowered
      inhibition by RCSF-THP, but not by N-THP. At 40 mg/l, inhibition by N-THP was 27
      +/- 9% vs. -43 +/- 8% by RCSF-THP (P = 0.001), i.e., all stone former THP
      promoted Ac. With an additional 3.5 mM of citrate, inhibition of Ac was 56 +/- 5%
      by normal and 34 +/- 6% by stone former THP (P = 0.021), and all seven stone
      former THP again inhibited Ac. Vi of RCSF-THP was higher than that of N at basal
      conditions (162 +/- 21 vs. 93 +/- 15 ml/g, P = 0.021) and in the presence of 5 mM
      calcium (352 +/- 54 vs. 118 +/- 17 ml/g, P = 0.001), i.e., RCSF-THP were more
      self-aggregated, but not when citrate was added (185 +/- 29 vs. 123 +/- 19 ml/g).
      (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285212
TI  - Differential expression and cellular distribution of mRNAs encoding alpha- and
      beta-isoforms of Na(+)-K(+)-ATPase in rat kidney.
AB  - We have used in situ hybridization histochemistry with isoform-specific,
      digoxigenin-labeled cRNA probes to characterize systematically the cellular
      distribution of mRNAs encoding alpha- and beta-subunit isoforms of the Na(+)-K(+)
      adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the normal rat kidney. Transcripts
      encoding the alpha 1-, alpha 2-, alpha 3-, beta 1-, and beta 2-subunits were
      detected in virtually all of the nephron segments, with prominent hybridization
      signal in the S3 segment of the proximal tubule, the cortical and medullary thick
      ascending limb of Henle's loop, the distal convoluted tubule, the cortical
      collecting duct along its entire length, and the renal pelvic epithelium. Several
      differences in the cell-specific pattern of expression of the various isoforms
      were observed. Among the alpha-isoforms, the alpha 3-subunit appeared to be
      preferentially expressed in the glomerular podocytes and mesangial cells,
      papillary interstitial cells, and renal pelvic epithelium. The beta-isoforms also
      differed in their distribution pattern, with the beta 1-subunit expressed to a
      greater degree in the glomerulus and renal pelvic epithelium and the beta 2
      subunit preferentially expressed in the papillary interstitial cells and
      papillary surface epithelium. The detection and expression pattern of alpha- and
      beta-subunit mRNAs in structures throughout the kidney is compatible with the
      possibility of six structurally unique Na(+)-K(+)-ATPase isozymes and suggests a
      potentially greater role for isozymes comprised of the alpha 2-, alpha 3-, and
      beta 2-subunits in renal sodium and potassium transport.

PMID- 8285213
TI  - Disparate effects of adenosine A1- and A2-receptor agonists on intrarenal blood
      flow.
AB  - Endogenous adenosine, secreted locally by the kidney during tissue hypoxia,
      induces heterogeneous renal hemodynamic responses. We investigated the cortical
      and outer medullary blood flow responses to intrarenal infusions of adenosine and
      adenosine A1- and A2-receptor agonists in anesthetized rats. These agents were
      infused into the renal interstitium through chronically implanted capsules, and
      blood flow was measured by laser-Doppler probes. Short (1 min, 0.05 ml)
      intrarenal infusions of adenosine (0.5 mumol) lowered cortical blood flow to 27
      +/- 10% of baseline (n = 7, P < 0.0005). Medullary blood flow response was
      biphasic, i.e., a transient decrease in flow to 52 +/- 8% of baseline (n = 17, P
      < 0.0001) followed by a more-sustained increase in flow to 135 +/- 6% (n = 17, P
      < 0.0001). N6-cyclopentyladenosine, an adenosine receptor A1 agonist, reduced
      both cortical and medullary blood flow to 59 +/- 4% (n = 10, P < 0.0001) and 38
      +/- 5% (n = 11, P < 0.0001) of baseline, respectively. By contrast, 2-[p-
      (carboxyethyl)phenethylamino]-5'-N-ethycarboxamidoadenosine (CGS-21680C), an
      adenosine receptor A2 agonist, increased dramatically the medullary blood flow to
      184 +/- 15% of baseline (n = 12, P < 0.0005), without major changes in cortical
      flow. We conclude that intrarenal adenosine reduces cortical blood flow and
      predominantly increases medullary flow via A1 and A2 receptors, respectively.
      These hemodynamic responses could play a role in protection of the outer medulla
      from hypoxia.

PMID- 8285214
TI  - Effect of fetal exposure to gentamicin on phosphate transport in young rat
      kidney.
AB  - The renal phosphate (Pi)-transporting capacity normally increases, due to
      increased carrier system affinity, during the third postnatal week in rats.
      However, the tubular Pi reabsorption of rat pups born from gentamicin-treated
      mothers does not increase during this period. This study determines whether
      exposure to gentamicin in utero selectively alters the postnatal maturation of
      the carrier affinity for Pi. Pi and glucose transports by proximal tubule brush
      border membrane (BBM) were studied. The maximal rate of uptake (Vmax) of Na-Pi
      cotransport was significantly lower (536 +/- 169 pmol.mg protein-1.10 s-1; n = 6,
      P < 0.01) in gentamicin-exposed rats than in controls (1,021 +/- 167 pmol.mg
      protein-1.10 s-1, n = 6), whereas the Michaelis constant (Km) values were the
      same. Gentamicin exposure had no effect on plasma parathyroid hormone
      concentration or on BBM glucose transport activity. The total phospholipid
      content of BBM, their phospholipid composition, cholesterol content, and
      cholesterol-to-total phospholipid mole ratio were unaltered, suggesting that
      membrane fluidity was unchanged. The Vmax of BBM alkaline phosphatase was lower
      in gentamicin-exposed rats than in controls.

PMID- 8285215
TI  - PTH-sensitive K(+)- and voltage-dependent Pi transport by chick renal brush
      border membranes.
AB  - Brush-border membrane vesicles (BBMV) from chick (Gallus gallus) kidneys were
      used to examine possible pathways of Pi transport associated with Pi secretion.
      Preloading with 6 mM Pi trans-stimulated 32Pi uptake in the absence of Na+,
      indicating facilitation. Inside-positive voltage (100 mM K+, out > in,
      +valinomycin) increased Pi uptake from 161 +/- 4.4 to 241 +/- 16.1 pmol.mg
      protein-1.5s-1 at pH 7.5 (in = out). Gradients characterized by extravesicular pH
      (pHo) of 5.5 vs. intravesicular pH (pHi) of 7.5, 100 mM K+ (out > in), without
      and with valinomycin, further increased uptake to 664 +/- 148.5 and 946 +/- 90.8
      pmol.mg protein-1.5s-1, respectively. Carbonyl cyanide m-chlorophenylhydrazone
      (CCCP) had no effect on the latter response, but with 100 mM K+ (in = out),
      valinomycin decreased the response more than one-half, implicating a H+ diffusion
      potential. Generation of this potential with pHo 5.5 vs. pHi 7.5 and CCCP did not
      drive concentrative Pi uptake in absence of K+. Parathyroid hormone (PTH)
      treatment significantly increased this BBMV K(+)- and voltage-dependent Pi up
      take compared with the parathyroidectomized (PTX) condition. The values of
      maximal uptake rate (Vmax) in PTH vs. PTX BBMV were 5,330 and 1,976 pmol.mg
      protein-1.5s-1, respectively. K(+)-dependent transport was inhibited by arsenate,
      phosphonoacetic acid, and vanadate. Together, the data indicate that this PTH
      sensitive, voltage- and K(+)-dependent monovalent Pi transporter could be the
      mechanism by which Pi exits, cell-to-lumen, during renal tubular Pi secretion.

PMID- 8285216
TI  - Basic amino acid transport in renal papilla: microinfusion of Henle's loops and
      vasa recta.
AB  - To determine whether basic amino acids, like acidic and neutral amino acids,
      could be reabsorbed distal to tips of Henle's loops and recycled between loops
      and vasa recta in the renal papilla, we continuously microinfused ascending
      Henle's loops and vasa recta with 14C-labeled L-lysine (L-Lys; 1.28 mM) or L
      arginine (L-Arg; 1.17 mM) and 3H-labeled inulin. We also determined percent of
      recovered radiolabel as intact amino acid. Like acidic and neutral amino acids,
      relative to inulin, approximately 30% of L-Lys and approximately 45% of L-Arg
      microinfused into Henle's loops were reabsorbed. However, whereas radiolabeled L
      Lys reabsorption, like reabsorption of acidic and neutral amino acids, was not
      readily inhibited, radiolabeled L-Arg reabsorption was reduced to approximately
      25% by addition of unlabled L-Arg (50 mM) or L-homoarginine (L-Homo-Arg) (50 mM)
      to infusate. This observation provides greater evidence for specific, carrier
      mediated reabsorption for L-Arg than for acidic or neutral amino acids. About 36%
      (relative to inulin) of each of these amino acids microinfused into ascending
      vasa recta apparently was transferred directly into ipsilateral tubular
      structures (probably thin descending limbs of Henle's loops). Transfer of
      radiolabeled L-Arg was reduced to approximately 8% by the inclusion of unlabeled
      L-Arg (50 mM) in infusate. Transfer of unlabeled L-Lys was unaffected by
      inclusion of unlabeled L-Lys (50 mM) in infusate but was reduced to approximately
      20% by inclusion of unlabeled L-Arg (50 mM) or L-Homo-Arg (50 mM) in infusate.
      (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285217
TI  - Cystine loading induces Fanconi's syndrome in rats: in vivo and vesicle studies.
AB  - To better understand the link between lysosomal cystine accumulation and the
      renal impairment seen in cystinosis, we have studied the effect of cystine
      loading in vivo, on renal function of rats, and in brush-border membrane vesicles
      (BBMV) prepared from the kidney cortex of the treated rats. Intraperitoneal
      injection of cystine dimethyl ester (CDME) (400 mumol, twice a day, for 5 days)
      led to an increased urine volume and excretion of glucose, phosphate, and
      protein. Kinetic analysis of alpha-methylglucoside initial flux in BBMV showed
      reduction in maximal transport capacity (Vmax, from 10.1 +/- 1.3 to 8.5 +/- 0.7
      nmol.min-1.mg protein-1; P < 0.01) with no change in Michaelis constant (Km, 4.80
      +/- 0.08 and 4.90 +/- 0.05 mM). The number of phlorizin binding sites declined
      (from 6.5 +/- 0.7 to 4.1 +/- 0.4 pmol/mg protein; P < 0.01) with no significant
      change in the affinity for phlorizin (0.64 +/- 0.08 and 0.59 +/- 0.06 microM). In
      the cortex homogenate, cystine concentration, which was undetectable in controls,
      increased to 0.97 +/- 0.09 nmol 1/2 cystine/mg protein. Two hours after CDME
      administration, ATP content declined to approximately 50% of control values. This
      decline was transient, and ATP content was recovered to control values 5 h after
      CDME administration. The treatment did not affect ouabain-sensitive
      adenosinetriphosphatase activity (40.0 +/- 3.9 and 38.6 +/- 4.7 nmol Pi.mg
      protein-1.min-1) or the number and affinity of ouabain binding sites (Bmax = 1.48
      +/- 0.25 and 1.44 +/- 0.18 pmol/mg, and Kd = 0.68 +/- 0.09 and 0.72 +/- 0.12
      microM, respectively). (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285218
TI  - Angiotensin receptor sites in renal vasculature of rats developing genetic
      hypertension.
AB  - The purpose of the present study was to characterize angiotensin II (ANG II)
      receptors in renal resistance vessels of young spontaneously hypertensive rats
      (SHR) ANG II receptor subtypes were evaluated in biochemical and functional terms
      using nonpeptide ANG II antagonists of the types AT1 (Dup-753 and Dup-532) and
      AT2 (PD-123319 and CGP-42112). In vitro radiolabeled ligand binding studies were
      performed on preglomerular resistance vessels freshly isolated from kidneys of
      SHR and Wistar-Kyoto (WKY) rats. The method of isolation and purification of
      renal microvessels was based on iron oxide infusion into the kidneys and
      separation of the vessels with the aid of a magnetic field followed by successive
      passages through various sized sieves. Physiological receptor expression was
      evaluated in vivo by measuring renal blood flow responses to ANG II injected
      alone and in a mixture with a receptor antagonist into the renal artery of
      indomethacin-treated rats. Our results indicate the existence of at least two
      functional (vasoconstriction mediating) subtypes of ANG II receptors sites in the
      renal microcirculation. Eighth percent of the ANG II receptor sites displayed
      high affinity to Dup-753 and Dup-532 and low affinity to PD-123319 and CGP-42112,
      whereas the remaining 20% of sites showed low affinity to Dup-753 and Dup-532 and
      CGP-42112 and intermediate affinity to PD-123319. In addition, the renal
      vasculature of young SHR and WKY displays similar ANG II receptor characteristics
      and identical blood flow responses to ANG II and to mixtures of ANG II and its
      antagonists.

PMID- 8285219
TI  - H-K-ATPase in distal renal tubular acidosis: urinary tract obstruction, lithium,
      and amiloride.
AB  - In previous studies we suggested that urinary tract obstruction and chronic
      administration of lithium or amiloride were models of "voltage-dependent" distal
      renal tubular acidosis (DRTA). Subsequently, differences among these three models
      suggested that the pathogenesis was far more complex than we originally proposed.
      A recent study showed that H-adenosinetriphosphatase (H-ATPase) activity was
      decreased in all three experimental models. In the current experiments we
      examined the effect of 24-h unilateral ureteral obstruction (UUO) and chronic
      administration of amiloride and lithium on collecting tubule H-K-ATPase, the
      other renal H-ATPase enzyme. In the obstructed kidney, cortical collecting tubule
      (CCT) H-K-ATPase activity was enhanced by 73 +/- 10.0%, whereas the enzyme
      activity in medullary collecting tubule (MCT) was decreased by 67 +/- 5.4%. In
      the normal contralateral kidney, activities of H-ATPase, H-K-ATPase, and Na-K
      ATPase were increased by approximately 30% in both CCT and MCT. Following
      amiloride (3 mg.kg-1.day-1 x 3 days ip), rats had normal acid-base status, slight
      hyperkalemia, and markedly elevated plasma aldosterone levels. Both CCT and MCT H
      K-ATPase activities in amiloride-treated rats were unchanged. After LiCl (4
      meq.kg-1.day-1 x 3 days ip), rats developed mild metabolic acidosis and had
      normokalemia and normal aldosterone status. CCT H-K-ATPase activity in lithium
      treated rats was decreased by 64 +/- 8.8%, whereas the enzyme activity in MCT
      remained unchanged. Lithium in vitro (30 meq/l) inhibited CCT, but not MCT, H-K
      ATPase activity, whereas amiloride had no effect on the enzyme activity.
      (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285220
TI  - Segmental differences in angiotensin receptor subtypes in interlobular artery of
      hydronephrotic rat kidneys.
AB  - Recent studies demonstrate that angiotensin II (ANG II)-induced vascular action
      is mediated preferentially by AT1 receptors. Although autoradiographic studies
      indicate the presence of AT2 receptors in large preglomerular vessels, functional
      roles for AT2 receptors in ANG II-induced renal vasoconstriction remain
      undetermined. We examined the effects of DuP-753 and PD-123319 on ANG II-induced
      vasoconstriction of interlobular arteries (ILA) in isolated perfused
      hydronephrotic rat kidneys to directly assess the AT1- and AT2-mediated action of
      ANG II on renal microvessels. Both DuP-753 (0.1-10 microM) and PD-123319 (0.1-10
      microM) elicited dose-dependent vasodilation of ANG II-induced ILA constriction,
      with 86 +/- 4% and 36 +/- 4% inhibition by 10 microM DuP-753 and PD-123319,
      respectively. The reversal by DuP-753 of ANG II-induced ILA vasoconstriction was
      greater in small-caliber segments than in large-caliber segments. In contrast,
      the ability of PD-123319 (10 microM) to inhibit the vasoconstriction was
      augmented as the vessel diameter increased (slope = +0.46, correlation
      coefficient = +0.68; P < 0.01). Thus, although AT1 predominantly mediates the ANG
      II-induced ILA vasoconstriction, PD-123319-sensitive ANG II receptors (e.g., AT2
      or AT1B) may also participate partly in the ILA vasoconstriction, particularly at
      large-caliber segments. In conclusion, distribution of ANG II receptor subtypes
      may differ depending on the size of the renal microvasculature.

PMID- 8285221
TI  - Expression and characterization of a new species of 11 beta-hydroxysteroid
      dehydrogenase in Xenopus oocytes.
AB  - 11 beta-Hydroxysteroid dehydrogenase (11-OHSD) plays a critical role in
      conferring aldosterone specificity to mineralocorticoid target cells. We have
      recently described a novel isoform of 11-OHSD in the collecting duct (11
      OHSD/CD), which differs from the previously characterized isoform (11-OHSD-1) in
      kinetic parameters, cofactor dependency, and reversibility of the reaction.
      Unlike 11-OHSD-1, the collecting duct enzyme catalyzes irreversible
      dehydrogenation of endogenous glucocorticoids, has a very high affinity for its
      substrate, and is located in mineralocorticoid target cells; it thus appears well
      suited to "protect" the mineralocorticoid receptors from occupancy by
      glucocorticoids. As a first step in attempting to isolate the cDNA for the 11
      OHSD/CD isoform, we isolated mRNA from immunodissected cortical collecting duct
      (CCD) cells and characterized the 11-OHSD in oocytes injected with this mRNA.
      Water-injected oocytes had no measurable 11-OHSD activity. In contrast, oocytes
      injected with as little as 1 ng CCD mRNA expressed detectable 11-OHSD activity.
      Expression of 11-OHSD activity was dependent on the amount of mRNA injected and
      was maximal with 30 ng mRNA. Similar to the findings in CCD cells, the expressed
      enzyme preferred NAD over NADP (activity was 0.46 +/- 0.04 and 0.011 +/- 0.01
      fmol.min-1.oocyte-1 with 0.1 mM NAD and NADP, respectively). The Michaelis
      constant (Km) for corticosterone was 11.5 +/- 3.7 nM. Similar to the findings in
      CCD cells, the expressed enzyme worked predominantly in the oxidative direction,
      as back-conversion of [3H]dehydrocorticosterone to corticosterone was negligible.
      (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285222
TI  - Enhanced myogenic activation in skeletal muscle arterioles from spontaneously
      hypertensive rats.
AB  - The purpose of this study was to determine whether the vascular myogenic response
      is enhanced in hypertension. Experiments were conducted in the intact cremaster
      muscle microcirculation as well as in isolated arterioles of hypertensive (SHR)
      and normotensive (WKY) rats. Increasing venous pressure in vivo by approximately
      5 mmHg had no effect on normotensive first- (1A) or third-order arteriolar (3A)
      diameters; in contrast, hypertensive 1A diameter decreased 4% (89 +/- 2 to 85 +/-
      3 microns) with an 8% decrease in 3A (24 +/- 2 to 22 +/- 2 microns). To further
      examine this enhanced constriction to elevated intravascular pressure in SHR,
      diameter was monitored in isolated 1A during step increases and decreases in
      intraluminal pressure. Normotensive arterioles displayed myogenic responses
      between pressures of 50 and 170 cmH2O; in contrast, hypertensive arterioles
      demonstrated myogenic responses over an extended pressure range (50-210 cmH2O).
      In addition, the change in diameter for each step change in pressure was greater
      in the arterioles from SHR, indicating an increased myogenic responsiveness. The
      myogenic reactions were unaffected by alpha-receptor blockade with phentolamine
      (10(-6) M), indicating that adrenergic hypersensitivity was not involved in the
      enhanced response to stretch. Morphometric analysis of the vascular wall revealed
      no differences in wall thickness, cross-sectional wall area, or wall-to-lumen
      ratio between normotensive and hypertensive rats. The length-tension
      relationships for normotensive and hypertensive rats demonstrated that peak
      active tension occurred at nearly the same vascular smooth muscle length. In
      addition, SHR arterioles were capable of maintaining higher levels of active
      tension that WKY arterioles, indicating an altered length-tension curve in
      chronic arterial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285223
TI  - Continuous pulmonary C-fiber stimulation produces sustained reflex cardiovascular
      depression.
AB  - We used an isolated perfused in situ left lung preparation to evaluate the
      hemodynamic response to specific pulmonary C-fiber stimulation with capsaicin in
      two groups of anesthetized dogs. In one group (n = 6), continuous administration
      of capsaicin at 5 micrograms.kg-1.min-1 into the isolated pulmonary circulation
      produced sustained (20 min) reflex decreases in mean arterial pressure, cardiac
      output, maximal left ventricular rate of pressure over time, and heart rate.
      These effects were abolished by vagotomy. In a second group (n = 5) of
      atropinized dogs, a mild hemorrhage was first performed in each dog during
      control conditions (capsaicin vehicle administration). The hemorrhage was
      performed by removing 10% of blood volume over 3 min and then replacing this
      blood 3 min later. After reinfusion and stabilization, the mild hemorrhage was
      repeated during continuous administration of capsaicin (6.0 +/- 1.0 microgram.kg
      1.min-1) into the isolated pulmonary circulation. The decrease of mean arterial
      pressure in response to hemorrhage was significantly greater during capsaicin
      administration than during control conditions. Lung denervation prevented the
      effect of capsaicin administration on the response to hemorrhage. We concluded
      that continuous pulmonary C-fiber stimulation produces sustained cardiovascular
      depression and compromises the hemodynamic response to mild hemorrhage in dogs.
      This latter effect may represent a central alteration of baroreflex gain.

PMID- 8285224
TI  - Inhibitory role of capsaicin-sensitive afferent neurons and nitric oxide in
      hemostasis.
AB  - Capsaicin-sensitive afferent neurons control blood flow via release of peptide
      transmitters and formation of nitric oxide (NO). The present study examined
      whether capsaicin-sensitive afferent neurons and NO interact in the control of
      hemostasis. Afferent nerve ablation by pretreating rats with a neurotoxic dose of
      capsaicin (125 mg/kg) led to a 26% reduction of the time of bleeding from
      punctured small mesenteric arteries in pentobarbital-anesthetized animals.
      Blockade of NO formation by NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg)
      attenuated the bleeding time in capsaicin-pretreated rats but had no effect in
      vehicle-pretreated rats. Platelet aggregation induced by ADP was significantly
      augmented by 12% in capsaicin-pretreated rats. L-NAME did not alter platelet
      aggregation in vehicle-pretreated rats but enhanced it in capsaicin-pretreated
      animals. The prothrombin and partial thromboplastin time and the plasma levels of
      fibrinogen and antithrombin III remained unchanged by capsaicin or L-NAME,
      whereas the thrombin time was reduced in capsaicin-pretreated rats. These data
      indicate that capsaicin-sensitive afferent neurons play an inhibitory role in
      platelet aggregation and hemostasis, a function in which they interact with the
      NO system.

PMID- 8285225
TI  - Sieving of electrolytes at capillary wall of cat skeletal muscle by osmotic water
      flow.
AB  - To test the hypothesis that a significant proportion of transcapillary water flow
      occurs through solute-restricting channels, we investigated the effects of
      transcapillary water movement on plasma electrolytes in isolated perfused cat
      skeletal muscle. The lower hindlimbs of anesthetized cats were perfused with a
      plasma-albumin solution and were weighed to determine transcapillary water
      movement. Osmolality was increased 60-70 mosmol/kgH2O with sucrose, creating
      water fluxes of 8-10 ml.min-1.100 g-1, and the changes in the venous
      concentrations of sodium, potassium, and chloride were determined. The ion
      concentrations were all reduced by 6-7% with no significant difference between
      them. The amount of reduction was quantitatively explained by the flow of ion
      free water from the interstitial space into plasma and the diffusion of
      electrolyte in the same direction. These findings support the hypothesis that
      important water-only transcapillary channels exist in mammalian skeletal muscle.
      The observations may also explain some of the electrolyte changes seen in intense
      exercise.

PMID- 8285226
TI  - Thyroxine effects on temperature dependence of ionic currents in single rabbit
      cardiac myocytes.
AB  - Macroscopic whole cell currents were measured from single rabbit cardiac
      myocytes, using the suction electrode voltage-clamp technique, under euthyroid,
      hyperthyroid, and hypothyroid conditions. In ventricular myocytes, the
      temperature dependence of the transient outward current (I(t)) was greatly
      reduced in hyperthyroid conditions, with Q10 values (between 22 and 32 degrees C)
      reduced from normal values of 6.14 +/- 0.93 (SE, n = 8) to 2.14 +/- 0.14 (n = 6).
      In contrast, two of the other major currents in these cells were relatively
      unaffected. Under hyperthyroid conditions, there was very little change in the
      amplitudes or temperature dependence of L-type calcium currents and of steady
      state currents, which reflect mainly the inwardly rectifying potassium current.
      In atrial cells no changes in the temperature dependence of I(t) were observed,
      with virtually identical Q10 values (close to 4) in eu- and hyperthyroid
      conditions. Under hypothyroid conditions, there was no change in the temperature
      dependence of I(t) in either ventricular or atrial cells. We conclude that the
      regulation of I(t) in ventricular cells is unique, rendering it extremely
      sensitive to temperature changes and to elevations in thyroxine levels. These
      results are discussed in the context of long-term regulation of ionic channels.

PMID- 8285227
TI  - Hemodynamic and mechanical determinants of myocardial O2 consumption in normal
      human heart: effects of dobutamine.
AB  - The relationship of myocardial O2 consumption (MVO2) to its potential hemodynamic
      and mechanical determinants was investigated in eight healthy normal volunteers
      at rest and during infusion of dobutamine (5-10 micrograms.kg-1.min-1). MVO2 was
      calculated from the monoexponential myocardial clearance of [1-11C]acetate with
      positron emission tomography, and left ventricular mechanical function was
      assessed by two-dimensional echocardiography. Infusion of dobutamine increased
      heart rate by 53%, the tension-time index by 31%, and the rate-pressure product
      by 116%. Cardiac output (+70%), left ventricular ejection fraction (+24%), total
      mechanical energy [systolic pressure-volume area, (PVA) +84%], and left
      ventricular pressure-work index (+100%) also increased during infusion of
      dobutamine. During infusion of dobutamine, MVO2 increased from 96 +/- 17 to 233
      +/- 19 J.min-1.100 g left ventricle-1, while myocardial efficiency (the ratio of
      PVA to MVO2) decreased from 46 +/- 8 to 35 +/- 4% (P < 0.001 each). MVO2 was best
      correlated (P < 0.001) with the PVA (r = 0.92) and the pressure-work index (r =
      0.92). Infusion of dobutamine also resulted in a significant parallel upward
      shift of the PVA-MVO2 relationship, indicative of an increase in PVA-independent
      MVO2. Our data indicate that, in human subjects, MVO2 is mainly related to
      systolic PVA and that inotropic stimulation with dobutamine results in decreased
      efficiency of contraction, such as that previously described in isolated hearts.

PMID- 8285228
TI  - Adaptation speed of cardiac mitochondrial oxygen consumption decreases with
      higher heart rate.
AB  - The purpose of the present study was to determine whether the mean response time
      of cardiac mitochondrial oxygen consumption after a step in metabolic demand is
      constant in heart muscle, as has already been found for skeletal muscle. The mean
      response time reflects the average delay between the change in ATP hydrolysis due
      to a heart rate step and mitochondrial ATP production. Isolated rabbit hearts
      with a water-filled balloon in the left ventricle were perfused according to
      Langendorff with a constant flow of Tyrode solution at 28 degrees C. The mean
      response time increased significantly from 7.6 s for a step in heart rate from 60
      to 70 min-1 to 12.1 s for a step from 60 to 120 min-1. The mean response times
      for heart rate steps downward from 120 min-1 were all approximately 12 s, but for
      the step from 120 to 140 min-1 the response time was 16.8 s. These results
      demonstrate that the mean response time of cardiac mitochondrial oxygen
      consumption in most cases increases with heart rate. These findings are in
      contrast to those obtained in skeletal muscle, where the response time at which
      ATP synthesis adapts to a change in work load is constant.

PMID- 8285229
TI  - Nitric oxide-induced microvascular permeability alterations: a regulatory role
      for cGMP.
AB  - This study evaluated the physiological effects of compounds that alter guanosine
      3',5'-cyclic monophosphate (cGMP) on the increase in vascular protein clearance
      induced by nitric oxide (NO) synthesis inhibition in the feline small intestine.
      A lymphatic vessel draining the small bowel was cannulated; vascular protein
      clearance and intestinal blood flow were measured. N omega-nitro-L-arginine
      methyl ester (L-NAME), the NO inhibitor, was infused (0.5 mumol/min) into the
      superior mesenteric artery. Vascular protein clearance increased approximately
      4.6-fold, whereas blood flow decreased to 50% of control. Elevation of cGMP by 1)
      cytosolic guanylate cyclase activation with a NO donor (SIN 1) or 2) a cGMP
      analogue, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) completely
      prevented the rise in microvascular permeability associated with L-NAME.
      Moreover, these compounds reduced (almost 90%) baseline vascular protein
      clearance, whereas inhibition of cytosolic guanylate cyclase with methylene blue
      significantly increased this parameter. Atrial natriuretic factor (ANF) has been
      reported to increase tissue cGMP levels and microvascular permeability. In this
      study, ANF did indeed increase intestinal microvascular permeability however this
      occurred independent of changes in intestinal cGMP levels. These data support a
      role for cGMP associated with NO-induced microvascular permeability alterations
      and raise the possibility that ANF has a cGMP-independent effect on microvascular
      permeability within the intestine.

PMID- 8285230
TI  - Cardiac desensitization to adenosine analogues after prolonged R-PIA infusion in
      vivo.
AB  - To determine the effects of chronic in vivo stimulation of adenosine receptors, R
      (-)-N6-(2-phenylisopropyl)adenosine (R-PIA), a selective A1 receptor agonist, was
      administered to rats as a continuous 7-day infusion (200 nmol/h). Inotropic and
      chronotropic responses of isolated atria to adenosine receptor agonists were
      markedly desensitized compared with the responses of atria from age-matched
      control animals. Carbachol's negative chronotropic effect was also attenuated,
      indicating a heterologous mode of desensitization. Antagonist radioligand binding
      assays indicated a 52% reduction in A1 adenosine receptor maximum binding, and
      competition binding assays revealed a significant loss of G protein-coupled high
      affinity A1 receptors in atria from R-PIA-treated rats. Inhibitory G proteins
      (Gi) were significantly reduced, as quantified by immunoblot analysis, with no
      change in the amount of stimulatory G proteins. Ventricular membranes from R-PIA
      rats showed loss of Gi and uncoupling of A1 receptors, without a significant
      change in A1 receptor density. Thus chronic R-PIA infusion desensitized rat
      atrial muscle to the effects of adenosine receptor agonists via several
      regulatory adaptations, including downregulation of A1 adenosine receptors,
      uncoupling of A1 receptors from their associated G proteins, and loss of Gi
      proteins.

PMID- 8285231
TI  - Carotid baroreflex responsiveness during dynamic exercise in humans.
AB  - We utilized 5-s changes of neck pressure and neck suction (from 40 to -80 Torr)
      to alter carotid sinus transmural pressure in seven men with peak oxygen uptake
      (VO2peak) of 41.4 +/- 3.6 ml O2.kg-1.min-1. Peak responses of heart rate (HR) and
      mean arterial pressure (MAP) to each carotid sinus perturbation were used to
      construct open-loop baroreflex curves at rest and during exercise at 25.7 +/- 1.1
      and 47.4 +/- 1.9% VO2peak. The baroreflex curves were fit to a logistic function
      describing the sigmoidal nature of the carotid sinus baroreceptor reflex. Maximal
      gain for baroreflex control of HR (-0.31 +/- 0.05 beats.min-1.mmHg-1) and MAP (
      0.30 +/- 0.08 mmHg/mmHg) at rest was the same as during exercise at 25 and 50%
      VO2peak (-0.30 +/- 0.05, -0.39 +/- 0.13 beats.min-1.mmHg-1 for HR, P = NS; -0.23
      +/- 0.04, -0.60 +/- 0.38 mmHg/mmHg for MAP, P = NS). Resetting of the baroreflex
      occurred during exercise at 50% VO2peak. The centering point, threshold, and
      saturation pressures were significantly increased for baroreflex control of HR
      (delta pressure = 26.3 +/- 6.8, 19.6 +/- 10.4, 33.0 +/- 5.6 mmHg, P < 0.05) and
      MAP (delta pressure = 27.1 +/- 7.7, 16.1 +/- 14.8, 38.2 +/- 8.5 mmHg, P < 0.05).
      The operating point (steady-state HR and MAP) was shifted closer to threshold of
      the baroreflex during exercise at 50% VO2peak, as reflected by differences in HR
      and MAP between the centering and operating points (delta HR = 12.5 +/- 4.7
      beats/min, P = 0.10; delta MAP = 7.6 +/- 1.3 mmHg, P < 0.05). These findings
      suggest a resetting of the carotid baroreflex during exercise with no attenuation
      in maximal sensitivity. A shift in operating point toward threshold of the
      baroreflex enables effective buffering of elevations in systemic blood pressure
      via reflex alterations in HR and MAP.

PMID- 8285232
TI  - Response of arterial resistance and critical pressure to changes in perfusion
      pressure in canine hindlimb.
AB  - The dynamic pressure-flow relationship in the canine hindlimb at normal arterial
      pressure is best explained by modeling a Starling resistor (critical pressure,
      Pcrit) at the level of the arterioles. Regulation of flow can therefore occur at
      the Starling resistor through changes in Pcrit or along the length of the vessel
      through changes in arterial resistance (Ra). We hypothesized that increasing
      perfusion pressure (Pper) would increase Pcrit due to the myogenic response but
      would decrease Ra because of flow-mediated vasodilation and passive effects. We
      pump-perfused vascularly isolated hindlimbs of anesthetized dogs and then
      measured Pcrit and calculated Ra over Pper range of 75-175 mmHg. When Pper was
      increased from 75 to 175 mmHg, Pcrit increased from 33 +/- 2 to 48 +/- 6 (means
      +/- SE) mmHg, whereas Ra decreased from 10.1 +/- 1.2 to 7.86 +/- 0.7 mmHg.min.100
      g.ml-1 (P < 0.01). Thus the responses of Pcrit and Ra to an increase in Pper were
      dissociated. In a second part of the study, we lowered carotid sinus pressure to
      determine the effects of central factors on local autoregulation. A decrease in
      carotid sinus pressure increased Pcrit and Ra at each Pper (P < 0.05). We
      conclude that an increase in Pper causes the arterial vasculature to constrict at
      the level of the Starling resistor and dilate more proximally. The carotid
      baroreflex causes an increase in tone throughout the arterial vasculature but
      does not alter the local response to increases in Pper.

PMID- 8285233
TI  - Ventriculographic evaluation in three rat models of cardiac dysfunction.
AB  - Chronic cardiac dysfunction was produced in rats by means of 1) aorto-caval
      fistula (A-V fistula), 2) coronary ligation, or 3) coronary embolization. Eleven
      to twelve weeks later, left ventricular ejection fraction (LVEF) was evaluated by
      ventriculography and compared with normal controls. A-V fistula decreased LVEF by
      13% and increased cardiac output (CO) by 82%. Coronary ligation and embolization
      produced a greater decrease in LVEF (-36% and -30%) and a decrease in CO (-36%
      and -29%). Systemic vascular resistance was significantly decreased in the A-V
      fistula (-47%) model but increased in both ligation and embolization models (by
      99 and 87%). LV end-diastolic volume was increased in fistula or ligation (by 68
      and 36%), whereas there was no change in rats with embolization. LV end-systolic
      volume and LV end-diastolic pressure were significantly increased in all three
      models. Plasma atrial natriuretic factor was increased by 676% with fistula, 212%
      with ligation, and 113% with embolization. There was no significant change in
      plasma renin activity or catecholamines in any of the models. We concluded that
      coronary embolization and ligation are effective methods of producing chronic LV
      dysfunction in rats, as evidenced by the significant decrease in LVEF. On the
      other hand, A-V fistula is an appropriate model of myocardial hypertrophy with
      greatly increased plasma atrial natriuretic factor, but cardiac dysfunction was
      minimal as indicated by the mild decrease in LVEF.

PMID- 8285234
TI  - Cytosolic calcium transients in myocytes isolated from rats with ischemic heart
      failure.
AB  - Mechanical performance and cytosolic Ca2+ dynamics were characterized in myocytes
      isolated from left and right ventricles of rats with ischemic heart failure.
      Seven days after coronary artery narrowing (CAN) in rats filling pressures were
      elevated, whereas systolic pressures and ejection of blood were depressed. Left
      ventricular myocytes increased 18% in length and 19% in width, whereas right
      myocytes expanded longitudinally by 23% and transversely by 24%. Contractile
      behavior of myocytes displayed reductions in myocyte shortening and velocity of
      shortening, despite prolongation of time to peak shortening. Diastolic Ca2+
      increased by 32 and 39% in left and right myocytes of CAN animals, whereas peak
      systolic Ca2+ in left ventricular myocytes was depressed (22%). Time to peak Ca2+
      was prolonged by 68% in left myocytes. Moreover, time required for peak Ca2+ to
      return to diastolic levels was prolonged in left myocytes. Regression analysis
      revealed correlations between end-diastolic pressure and diastolic Ca2+ and peak
      developed pressure and systolic Ca2+. Thus ischemic heart failure finds its
      cellular basis in a depression in myocyte contractility that may in turn be due
      to alterations in cytosolic Ca2+ handling.

PMID- 8285235
TI  - Regulation of L-arginine synthesis from L-citrulline by L-glutamine in
      endothelial cells.
AB  - L-Arginine synthesis from L-citrulline was studied in cultured bovine venular,
      bovine aortic, human microvascular, and cloned human microvascular endothelial
      cells (EC). L-Citrulline was actively recycled into L-arginine in all four EC
      lines, with similar rates between venular and aortic EC. L-Arginine synthesis
      from L-citrulline was very sensitive to extracellular L-citrulline concentrations
      in the range normally found in plasma (50-100 microM). L-Glutamine (0.5mM)
      decreased L-arginine synthesis from L-citrulline, whereas 0.5 mM L-arginine, L
      alanine, L-glutamate, or L-lysine had no effect. In contrast to the findings in
      intact cells, 1 mM L-glutamine had no effect on L-arginine synthesis from L
      citrulline in EC lysates. Similarly, L-glutamine (1 mM) had no effect on the
      conversion of argininosuccinate to arginine in EC lysates. L-Glutamine (0.5 and 1
      mM), but not 0.5 mM L-arginine, L-alanine, L-glutamate, or L-lysine, inhibited L
      citrulline transport by EC. The inhibition of L-citrulline transport by L
      glutamine was dose dependent and competitive in nature. These results suggest
      that L-glutamine decreased L-arginine synthesis from extracellular L-citrulline
      by interfering with its transport. Inasmuch as nitric oxide (NO) and L-citrulline
      are constantly generated from L-arginine, with L-citrulline being actively
      converted into L-arginine in venular, microvascular, and aortic EC, our data
      indicate a functioning intracellular arginine-citrulline cycle in these cells.
      This cycle may function to efficiently scavenge the carbon and alpha-amino group
      of L-arginine and to maintain a sufficient cellular concentration of L-arginine
      during prolonged synthesis of NO in EC. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285236
TI  - Cyclic nucleotides and cerebrovascular tone in newborn pigs.
AB  - Relationships between cyclic nucleotides and cerebrovascular tone were
      investigated using closed cranial windows in anesthetized newborn pigs. Pial
      arteriolar diameter was monitored and cerebrospinal fluid (CSF) was collected
      from beneath the cranial window. Adenosine 3',5'-cyclic monophosphate (cAMP) and
      guanosine 3',5'-cyclic monophosphate (cGMP) concentrations in CSF were 1,690 +/-
      200 and 730 +/- 40 fmol/ml, respectively. Topically applied isozyme-selective and
      nonselective inhibitors [3-isobutyl-1-methylxanthine (IBMX), theophylline, Ro
      201724, dipyridamole, zaprinast, calmidazolium, and W-7] of cyclic nucleotide
      phosphodiesterases dilated pial arterioles with concomitant increases in cAMP
      and/or cGMP levels in CSF. Topical application of dibutyryl-cAMP and dibutyryl
      cGMP also resulted in pial arteriolar dilation. Ten-minute hypercapnia, which
      results in pial arteriolar dilation, increased cAMP to 5,240 +/- 900 and cGMP to
      1,350 +/- 200 fmol/ml. IBMX and zaprinast potentiated the increases in cAMP and
      cGMP as well as the cerebrovascular dilation in response to hypercapnia. These
      data suggest that cyclic nucleotides contribute to regulation of cerebral
      vascular tone during control conditions. Furthermore, cAMP and/or cGMP appears to
      be involved in arterial vasodilation in response to hypercapnia in newborn pigs.

PMID- 8285237
TI  - ANP has no postsynaptic effect on autonomic regulation of cardiac pacemaker rate
      in the rat.
AB  - We studied whether atrial natriuretic peptide (ANP) influences sinoatrial node
      pacemaker activity or whether it modifies the response to activation of
      postsynaptic autonomic receptors. Male Sprague-Dawley rats were anesthetized with
      pentobarbital sodium (45 mg/kg). Their hearts were removed quickly and placed in
      physiological salt solution. The atria were isolated; the right intra-atrial
      chamber was exposed to allow intracellular recording from sinoatrial node
      pacemaker cells. The tissue was placed in a temperature-regulated recording
      chamber and superfused with warmed oxygenated physiological salt solution. With
      use of standard microelectrode recording techniques, action potentials were
      recorded from spontaneously depolarizing cells in the presence of muscarine (62.5
      500 nM) or norepinephrine (0.1 and 1.0 microM). Muscarine reduced the frequency
      of action potentials dose dependently, whereas norepinephrine increased their
      frequency. The addition of ANP (0.1-100 nM) to the superfusion had no effect on
      the frequency of action potentials during the superfusion of physiological salt
      solution or in the presence of either muscarine or norepinephrine. We conclude
      that ANP does not act on cardiac pacemaker cells to modulate the effect of
      neurotransmitters.

PMID- 8285238
TI  - Physiology of cardiac tamponade and paradoxical pulse in conscious dogs.
AB  - The physiological mechanism of paradoxical pulse in cardiac tamponade remains
      controversial. In eight conscious dogs with intact pericardia, ultrasonic
      dimension transducers assessed biventricular geometry and volumes, while
      micromanometers measured right ventricular (RV), left ventricular (LV), pleural,
      and pericardial pressures. With normal inspiration, peak LV pressure fell by 7.7
      +/- 1.3 mmHg at control and by 20.3 +/- 3.7 mmHg during tamponade (P < 0.001),
      consistent with the development of paradoxical pulse. At peak inspiration during
      tamponade, RV filling increased, the interventricular septum shifted leftward,
      transeptal pressure became negative, and LV septal arc length (l theta) became
      smaller than its respective unpreloaded value at maximal vena caval occlusion
      (l(o)). Analysis of stroke work (SW)-end-diastolic volume (EDV) and end-systolic
      pressure-volume coordinates at peak inspiration during tamponade revealed that
      end-systolic pressure was 19.1 +/- 10.2 mmHg below the baseline end-systolic
      pressure-volume curve (P < 0.01), and SW was 24.2 +/- 8.8% below the baseline SW
      EDV curve (P < 0.01), indicating transient inspiratory LV dysfunction. It is
      proposed that inspiratory leftward interventricular septal shifting at low LV EDV
      during tamponade completely unloads the septum (l theta < l o), eliminates the
      septal contribution to global LV SW, results in transient inspiratory LV
      dysfunction, and contributes to the phenomenon of paradoxical pulse.

PMID- 8285239
TI  - Sarcoplasmic reticulum-related changes in cytosolic calcium in pressure-overload
      induced feline LV hypertrophy.
AB  - Alterations in Ca2+ homeostasis that involve the sarcoplasmic reticulum (SR) were
      studied in feline left ventricular (LV) myocytes isolated from hearts with LV
      hypertrophy induced by slow, progressive pressure overload. At death, severe
      hypertrophy was evidenced by increased heart weight-to-body weight ratio (8.4 +/-
      0.6 vs. 4.2 +/- 0.2 g/kg in controls). Steady-state Ca2+ transients (measured as.
      indo 1 fluorescence at 410 nm/480 nm; I410/I480) in LV hypertrophy (LVH) myocytes
      had diminished peak amplitudes (I410/I480 2.28 +/- 0.07 vs. 2.53 +/- 0.07 in
      controls) and prolonged durations (0.75 +/- 0.03 vs. 0.59 +/- 0.02 s in
      controls). The magnitude of shortening was reduced and the contractile duration
      was prolonged in LVH myocytes. The idea that changes in SR function are
      responsible for these alterations in the Ca2+ transient was tested by studying
      two aspects of SR-related Ca2+ homeostasis. Restitution of releasable SR Ca2+ was
      studied by measuring indo 1 transients and contractions during premature beats.
      The time course of restitution of both the indo 1 transient and contraction of
      hypertrophy myocytes was significantly slower than in controls. These data
      suggest that restitution of releasable SR Ca2+ is slowed in hypertrophy myocytes.
      The reduction of the indo 1 transient and contraction in beats following long
      rest periods (rest decay) was measured to determine the rate of Ca2+ loss from
      the SR. Rest decay was significantly (P < 0.05) more pronounced in hypertrophy
      myocytes, suggesting that Ca2+ loss from the SR is accelerated in these myocytes.
      (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285240
TI  - NMR measurements of Na+ and cellular energy in ischemic rat heart: role of Na(+)
      H+ exchange.
AB  - Interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectra were
      continuously collected on perfused rat hearts subjected to low-flow ischemia (30
      min, 10% flow) or zero-flow ischemia (21 min) followed by reperfusion. During
      untreated low-flow and zero-flow ischemia, intracellular Na+ (Nai+) increased by
      53 +/- 11 (+/- SE) and 78 +/- 8%, respectively, and remained elevated for zero
      flow hearts. However, during both low- and zero-flow ischemia, Nai+ did not
      increase in hearts treated with the Na(+)-H+ exchange inhibitor, 5-(N-ethyl-N
      isopropyl)amiloride (EIPA). The pH decreases during ischemia were unchanged. EIPA
      treatment reduced ATP depletion during ischemia. During reperfusion from zero
      flow ischemia, EIPA-treated hearts displayed more rapid and extensive recoveries
      of phosphocreatine and ATP. Recovery of left ventricular developed pressure was
      improved for zero-flow hearts treated with EIPA during the ischemic period
      exclusively (104 +/- 13%) compared with untreated hearts (36 +/- 21%). These data
      indicate that Na(+)-H+ exchange is an important mechanism for Nai+ accumulation,
      but not for pH regulation, during myocardial ischemia. Additionally, Nai+
      homeostasis plays an important role in the postischemic recovery of cellular
      energy and ventricular function.

PMID- 8285241
TI  - Vasopressin and oxytocin: modulators of neurohypophysial blood flow.
AB  - We examined the role of arginine vasopressin (AVP) as a mediator of
      neurohypophysial (NH) blood flow regulation in anesthetized dogs. First, we
      evaluated the NH hyperemia that occurs during hemorrhagic hypotension in the
      presence (n = 7) and absence (n = 7) of the selective AVP-V1 receptor antagonist
      [d(CH2)5Tyr(Me)]AVP. AVP-V1 blockade did not alter NH transient or steady-state
      flow responses to a standardized decrease to 80 mmHg mean arterial blood
      pressure. We then determined whether exogenous AVP alters NH and regional
      cerebral blood flow (CBF) (n = 8). Sequential intracarotid infusions resulted in
      sagittal sinus blood AVP concentrations ranging from 6.97 +/- 3.3 x 10(3) to 2.45
      +/- 0.47 x 10(6) pg/ml. No change in NH blood flow (control 428 +/- 162 vs. 487
      +/- 75 ml.min-1.100 g-1) was observed even at the highest blood level. However,
      CBF at the highest AVP level increased from a control value of 20 +/- 3 to 40 +/-
      4 ml.min-1.100 g-1, while cerebral oxygen consumption remained unchanged.
      Administration of a selective AVP-V1 receptor antagonist, [d(CH2)5Tyr(Me)]AVP,
      blocked AVP-induced elevation in CBF in a third set of dogs (n = 5). Oxytocin was
      also given by intracarotid infusion at a constant rate (1-200 micrograms/ml) in a
      final group (n = 5). NH blood flow was unchanged at all doses, whereas CBF
      increased from control (24 +/- 2 to 38 +/- 5 ml.min-1.100 g-1) at the highest
      dose. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285242
TI  - NO is more important than PGI2 in maintaining low vascular tone in feto-placental
      vessels.
AB  - The endothelial cells of the human umbilical artery and vein release the
      vasodilators prostacyclin [prostaglandin (PG) I2] and nitric oxide (NO). However,
      the role of these two substances in the maintenance of vasodilator tone in the
      feto-placental circulation is not known. Studies were therefore undertaken to
      compare the relative release of PGI2 and NO from perfused segments (10 cm) of
      endothelium-intact human umbilical artery (HUA) and vein (HUV) utilizing the
      cascade bioassay. The endothelium-denuded bovine pulmonary arterial strip was
      used as the detector tissue because this tissue relaxes equally to various
      concentrations of PGI2 and S-nitroso-N-acetylpenicillimine (SNAP), which acts by
      releasing NO. The basal release of NO from the HUA was approximately five times
      greater than that of PGI2. After stimulation with A-23187, the release of NO from
      HUV was five to six times greater, and from the HUA, the release was three times
      greater compared with the PGI2. SNAP was significantly more potent compared with
      PGI2 in relaxing endothelium-denuded rings of human umbilical and chorionic plate
      arteries in vitro. These studies suggest that NO is more important than PGI2 for
      maintenance of low vascular tone in feto-placental vessels, because there is a
      greater release of NO from the HUA and HUV, and NO is more potent in relaxing
      endothelium-denuded feto-placental vessels in vitro relative to PGI2.

PMID- 8285243
TI  - Ventricular interaction and septal deformation: a model compared with
      experimental data.
AB  - Diastolic ventricular interaction is associated with septal shift and
      deformation, the consequences of which have not been fully assessed. A model was
      therefore developed to describe the mechanisms involved in interaction between
      the ventricles under different loading conditions. We assumed a circular cardiac
      minor-axis geometry surrounded by a pericardial membrane with the left ventricle
      (LV) and septum described by three layers. To define the equilibrium condition,
      we required the net force-balance at the right ventricular (RV)-LV intersection
      points to equal zero. The model was tested with and without consideration of
      bending forces associated with a change of curvature of a thick-walled structure.
      Model results were compared with data from animal experiments subjected to aortic
      and pulmonary constriction. LV and RV end-diastolic pressures as well as
      pericardial pressure were measured. In six dogs, septal segment length was
      measured using sonomicrometry, and in seven dogs, endocardial curvature was
      measured using echocardiography. Model and experimental results show that 1) with
      severe RV loading, septal inversion occurs at a negative transseptal gradient,
      and 2) the end-diastolic septal segment length continues to shorten after septal
      inversion during pulmonary constriction. Model simulation suggests that bending
      moments account for the septal curvature at zero transseptal pressure. In
      addition, the model predicts the shift in the pressure-area relationship of each
      ventricle by a change in loading of the opposite ventricle and predicts that
      large transmural gradients in stress and strain are associated with septal
      inversion. Thus the model and the experimental data agree and describe the
      important factors that modulate diastolic septal mechanics during acute
      differential ventricular loading.

PMID- 8285244
TI  - Determinants of midwall circumferential segmental length of the canine
      ventricular septum at end diastole.
AB  - The ventricular septum attaches to the insertion points of the ventricular free
      walls, separates, and is shared by both the left (LV) and right (RV) ventricles.
      Changes in the transseptal pressure gradient (PTS, the difference between LV and
      RV pressures) will change the stress in the septum and, therefore, the length of
      the septal segment (Ls). However, since most of the septal myocardial fibers are
      continuous with those of LV free wall and the septum appears to be an integral
      part of LV, one might also expect that if the LV transmural pressure (Plvtm; the
      difference between LV and pericardial pressure) is raised, Ls would increase even
      in the absence of any change in PTS. Therefore, we hypothesized that at end
      diastole, Ls depends on both Plvtm and PTS. To test this hypothesis, we measured
      Ls (sonomicrometry), LV and RV pressures (micromanometers), and pericardial
      pressure (flat liquid-containing balloon) in seven anesthetized open-chest dogs.
      Plvtm was increased through volume loading, whereas PTS was maintained constant
      at 10, 5, 0, -5, -10, and -15 mmHg by adjusting the degree of constriction of the
      pulmonary artery or aorta. These procedures were performed first with pericardium
      reapproximated and then after the pericardium had been opened widely. At each
      controlled PTS level, Ls increased linearly with the increase in Plvtm. Both the
      slope and the intercept of this Ls-Plvtm relation were affected by PTS in a
      nonlinear fashion. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285245
TI  - Echocardiographic assessment of LV mass in rabbits: models of pressure and volume
      overload hypertrophy.
AB  - We describe a method for the noninvasive measurement of left ventricular mass in
      small animals using two-dimensionally guided M-mode echocardiography. We compared
      echocardiographic cross-sectional area (CSA) and cubed-based volumetric indexes
      of left ventricular (LV) mass with postmortem wet weight in renovascular
      hypertension-induced pressure overload (group I) and acute aortic insufficiency
      induced volume overload (group II) models of ventricular hypertrophy. CSA and
      cubed echocardiographic indexes correlated well with wet weight from a
      combination of group I and II animals and their controls (r = 0.89, P < 0.001 for
      both groups). Separate analyses of groups I and II also demonstrated significant
      relationships between mass indexes and wet weight using CSA and cubed formulas,
      respectively, in both pressure (r = 0.57, P = 0.01 and r = 0.71, P < 0.001) and
      volume (r = 0.90 and r = 0.89, P < 0.001) overload models. Echocardiographically
      predicted LV mass derived from cubed and CSA regression formulas was 89 and 56%
      sensitive for pressure overload hypertrophy in group I and 100% sensitive (both
      cubed and CSA methods) for volume overload hypertrophy in group II. Cubed and CSA
      mass regression formulas were 60 and 80% specific for hypertrophy in group I and
      100 and 90% specific in group II. Normalization of predicted LV mass for body
      weight added little to the overall technique accuracy with measured sensitivities
      of 83 and 75% and specificities of 92 and 77%, respectively, for cubed and CSA
      methods. Two-dimensionally guided M-mode echocardiography provides a reasonably
      accurate method of LV mass determination in rabbits with pressure- or volume
      overloaded ventricles.

PMID- 8285246
TI  - Role of endothelium in sexual dimorphism in vasopressin-induced contraction of
      rat aorta.
AB  - In rat thoracic aorta, contractile responses to arginine vasopressin (AVP) are
      twofold higher in females than in males. To determine the role of the endothelium
      in this phenomenon, the effects of endothelium removal and inhibition of nitric
      oxide (NO) synthase and cyclooxygenase were examined in thoracic aortas prepared
      from male and female Sprague-Dawley rats and mounted for isometric tension
      recording. Maximal contractile response to AVP was substantially higher in female
      (4,232 +/- 316 mg/mg ring dry wt) than in male aortas (1,365 +/- 239; P < 0.01).
      Removal of the endothelium markedly potentiated maximal response to AVP in male
      aortas (4,100 +/- 422 mg/mg ring wt; P < 0.01); endothelium removal increased
      sensitivity but not maximal response in female aortas. Inhibition of NO synthase
      with NG-monomethyl-L-arginine (L-NMMA, 250 microM) doubled maximal contraction to
      AVP in male aortas (3,175 +/- 193 mg/mg ring wt; P < 0.01); L-NMMA increased
      sensitivity but not maximal response in female aortas. Inhibition of
      cyclooxygenase with indomethacin (10 microM) did not alter maximal response to
      AVP in male aortas but significantly attenuated responses of female aortas (2,816
      +/- 306 mg/mg ring wt; P < 0.01). In contrast, maximal contractile response to
      phenylephrine hydrochloride (PE) was 40% higher in males than in females (P <
      0.01); L-NMMA increased both the sensitivity and maximal response to PE to a
      greater extent in female (3,061 +/- 121 vs. 4,971 +/- 135 mg/mg ring wt; P <
      0.01) than in male aortas (4,317 +/- 227 vs. 4,899 +/- 104 mg/mg ring wt; P <
      0.01). (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285247
TI  - Dynamics of myocardial lactate efflux after a step in heart rate in isolated
      rabbit hearts.
AB  - We investigated whether a glycolytic burst contributes to the initial adaptation
      of ATP synthesis to increased cardiac metabolic demand. Six isolated rabbit
      hearts were perfused with glucose-containing Tyrode solution at 28 degrees C. In
      venous and arterial samples the lactate concentration was determined with a
      sensitive enzymatic cycling method. After the heart rate was doubled from 60 to
      120 beats/min, lactate efflux increased from 0.23 +/- 0.10 (SE) to 0.45 +/- 0.12
      mumol.min-1.g-1 dry weight with a mean response time of 21.3 s but without an
      overshoot. The transport time for lactate is longer than 15.7 s, suggesting that
      lactate production adapts with a mean response time of less than 6 s. Because no
      overshoot in lactate efflux was found, it is unlikely that a glycolytic burst
      after a step in heart rate contributes to the fast adaptation of ATP synthesis to
      demand in the isolated rabbit heart, although it might be possible that a change
      in cytosolic lactate production is not reflected in an increase in lactate
      efflux. Extrapolation of the results of this study to the in vivo situation
      should be done with caution.

PMID- 8285248
TI  - Reductions of myocardial Na-K-ATPase activity and ouabain binding sites in heart
      failure: prevention by nadolol.
AB  - To study the changes in myocardial digitalis binding sites in heart failure, we
      measured myocardial ouabain binding sites, Na-K-adenosinetriphosphatase (ATPase)
      activity, and ventricular muscle mechanical responses to acetylstrophanthidin in
      dogs with right-heart failure (RHF) produced by tricuspid avulsion and pulmonary
      artery constriction. Sham-operated dogs were studied as the control. RHF produced
      a significant decrease in ouabain binding sites in the right and left ventricular
      myocardium, which was accompanied by a proportional decrease in Na-K-ATPase
      activity. However, RHF and sham-operated dogs did not differ in systemic
      hemodynamic or right ventricular trabeculate muscle isometric contractile
      responses to acetylstrophanthidin. To determine whether chronic beta-adrenergic
      stimulation contributed to the development of Na-K-ATPase downregulation, we
      administered nadolol (40 mg/day) to a separate group of dogs during an early
      stage of RHF development. Nadolol effectively prevented the reduction of
      myocardial ouabain binding sites that occurred in RHF. Thus we conclude that
      myocardial ouabain binding sites and Na-K-ATPase activity are reduced in dogs
      with experimental heart failure and that these changes probably occur as a result
      of the attendant heightened sympathetic activity.

PMID- 8285249
TI  - Rigorous exercise training increases superoxide dismutase activity in ventricular
      myocardium.
AB  - Controversy exists as to the effect of endurance training on myocardial
      antioxidant enzyme activity. These experiments sought to clarify this issue by
      examining antioxidant enzyme activities in the rat ventricular myocardium in
      response to different intensities and durations of exercise training. Female
      Fischer-344 rats (120 days old) were assigned to either a sedentary control group
      or one of nine exercise training groups. Animals were exercised on a motorized
      treadmill for 10 wk; combinations of three durations (30, 60, and 90 min/day),
      and three levels of exercise intensity (low, moderate, and high) were studied.
      Exercise training did not alter (P > 0.05) citrate synthase, catalase, or
      glutathione peroxidase activities in the right or left ventricle. In contrast,
      high-intensity exercise (all durations) and moderate-intensity exercise (90
      min/day) resulted in a significant increase (P < 0.05; +28-30%) in right
      ventricular superoxide dismutase (SOD) activity. Similarly, high-intensity
      exercise training (all durations) resulted in a significant elevation (P < 0.05;
      +14-26%) of left ventricular SOD activity. Furthermore, low- and moderate
      intensity exercise training of long duration (i.e., 60-90 min/day) resulted in
      significant increases (P < 0.05; +10-23%) in left ventricular SOD activity. These
      data support the hypothesis that high-intensity exercise (> or = 30 min/day) or
      moderate-intensity exercise of long duration (> or = 60 min/day) is effective in
      upregulating SOD activity in the ventricular myocardium.

PMID- 8285250
TI  - End-systolic pressure length relations of stunned right and left ventricles after
      inotropic stimulation.
AB  - Regional end-systolic pressure-segment length relationships (ESPSLR) were used to
      compare the degree of right and left ventricular stunning induced by a 10-min
      occlusion of the left anterior descending coronary artery and the response to
      subsequent atrial pacing (50 beats/min above intrinsic heart rate) without and
      with dobutamine (2 micrograms.kg-1.min-1) in nine anesthetized open-chest pigs.
      From the ESPSLR, the slope (Ees) (at 100 mmHg for the left and 25 mmHg for the
      right ventricle) and the total area of the pressure-length relationship (PLA)
      were determined. From the latter, the distribution into external work (EW) and
      potential energy (PE) as well as the efficiency of energy transfer (EET = EW/PLA)
      were calculated. In both the stunned left and right ventricular myocardium Ees
      and EW were reduced according to the same linear regression equations (delta Ees
      = 0.7 Ees,baseline - 11.4, r2 = 0.86 and delta EW = 0.4 EWbaseline + 2.3, r2 =
      0.67), where Ees,baseline and EWbaseline are Ees and EW at baseline,
      respectively. EET of the stunned left and right ventricular segments decreased as
      PLA remained unchanged, due to an increase in PE. EET decreased from 0.84 +/-
      0.02 to 0.71 +/- 0.03 (P < 0.05) in the stunned right ventricular segment and
      from 0.71 +/- 0.02 to 0.44 +/- 0.03 (P < 0.05) in the stunned left ventricular
      segment. Atrial pacing did not affect EET with respect to stunning levels,
      whereas the additional infusion of dobutamine restored Ees, EW, and PE and
      consequently EET to baseline values. In conclusion, the right ventricle is
      susceptible to stunning. During atrial pacing the EET was lower than expected
      from the Ees, which could, in agreement with the time-varying elastance concept,
      be explained by an increase in afterload (a consequence of the decrease in stroke
      volume). Dobutamine not only increased Ees, EW, and EET but also restored the
      relationship between Ees and EET in both ventricular stunned segments.

PMID- 8285251
TI  - Role of L-arginine-derived nitric oxide in cholinergic dilation of gastric
      arterioles.
AB  - The role of L-arginine-derived nitric oxide (NO) in cholinergic vasodilation of
      resistance vessels was studied in the intact stomach of the rat, utilizing an in
      vivo microscopy technique. Two L-arginine analogues, NG-monomethyl-L-arginine (L
      NMMA) and nitro-L-arginine methyl ester (L-NAME), were used to block NO
      synthesis. Cholinergic dilation of gastric submucosal arterioles was induced by
      topical application of various concentrations of acetylcholine (ACh) (10(-7)-10(
      4) M). Intravenous but not topical administration of L-NMMA and L-NAME caused an
      increase in arterial pressure. Intravenous or topical L-NAME reduces resting
      arteriolar diameter. These findings support the contention that NO formation
      modulates basal vascular tone and suggest that NO release may play a significant
      role in the regulation of the gastric circulation. L-Arginine analogues
      attenuated the arteriolar dilating effect of ACh but not adenosine or
      nitroglycerin. Substantial arteriolar responses to ACh remained after systemic or
      topical treatment with either L-NMMA or L-NAME. These results indicate that the L
      arginine-NO pathway accounts only in part for ACh-induced vasodilation in gastric
      resistance vessels in vivo.

PMID- 8285252
TI  - Computer model of membrane current and intracellular Ca2+ flux in the isolated
      guinea pig ventricular myocyte.
AB  - This paper presents the equations and responses of a mathematical model that
      simulates the transmembrane current and intracellular concentrations of Ca2+
      ([Ca2+]), Na+ ([Na+]), and K+ ([K+]) of an isolated guinea pig myocyte. The
      structure of the model is closely related to the formulation of DiFrancesco and
      Noble (9). Quantitative values are based on a large number of experimental
      constraints, taken from the literature on isolated myocytes as well as our own
      experimental studies, that describe the properties of individual channels and
      integrated responses of whole cells under a variety of conditions. The model was
      constructed as a homeostatic system. The equilibrium of the model corresponds to
      the resting potential and intracellular ionic concentrations of unstimulated
      myocytes. The model generates deviations from equilibrium corresponding to the
      behavior of cells after stimulation of action potentials at different rates,
      blockade of Na-K-adenosinetriphosphatase (ATPase), reduction in extracellular
      [K+], and injection of constant depolarizing current. Simulations from the model
      suggest that changes in myoplasmic [Ca2+] at different stimulation rates, the
      generation of restitution and postextrasystolic potentiation, and the development
      of intracellular [Ca2+] oscillations arise simply from different interactions
      between uptake of Ca2+ into the sarcoplasmic reticulum via the Ca(2+)-ATPase,
      Ca(2+)-induced Ca2+ release of Ca2+ into the myoplasm, flux between regions of
      uptake and release, and leakage between sarcoplasmic reticulum and myoplasm. The
      model also demonstrates that a wide variety of basic electrophysiological
      responses of the isolated guinea pig myocyte can be simulated with quantitative
      precision by a single set of equations based on experimentally measured
      transmembrane current and intracellular [Ca2+] and [Na+].

PMID- 8285253
TI  - Endothelin-1 and -3 cause endothelium-dependent hyperpolarization in the rat
      mesenteric artery.
AB  - The present study was designed to determine whether endothelin (ET) induces
      endothelium-dependent hyperpolarization in the isolated rat mesenteric artery
      and, if so, to identify the receptor subtype involved. Main superior mesenteric
      arteries of Wistar-Kyoto and spontaneously hypertensive rats were used for the
      measurement of electrical responses of smooth muscle cells, using glass
      microelectrode. In tissues with endothelium of both strains, ET-1 (10(-8) M)
      caused an initial transient hyperpolarization followed by a sustained
      depolarization. In tissues without endothelium, only depolarization was observed.
      ET-3 (10(-8) M) produced transient hyperpolarizations only in preparations with
      endothelium. There was no significant difference in maximal amplitude of
      hyperpolarization between the two strains. BQ-123 (selective ETA-receptor
      antagonist) blocked the depolarization to ET-1 but did not inhibit
      hyperpolarizing responses to either isopeptide. IRL-1620 (specific ETB-receptor
      agonist) produced transient membrane hyperpolarizations in tissues with
      endothelium. The hyperpolarizations induced by ET were not affected by NG-nitro-L
      arginine. These data suggest that both ET-1 and ET-3 can cause endothelium
      dependent hyperpolarization in the rat mesenteric artery and that the endothelial
      receptor involved may belong to ETB subtype.

PMID- 8285254
TI  - Nicotine increases microvascular blood flow and flow velocity in three groups of
      brain areas.
AB  - To examine the mechanism of local cerebral blood flow (LCBF) elevation, nicotine
      (1.75 mg/kg sc) was administered to rats, and LCBF plus the distribution spaces
      of radiolabeled albumin (RISA) and red blood cells (RBC) in parenchymal
      microvessels were measured throughout the brain. Microvascular blood spaces and
      transit times were calculated from the data. From 1.5 to 3 min after nicotine
      administration, LCBF was raised by 40-150% in 16 of the brain areas and unaltered
      in the remaining 28 areas. The affected structures included parts of the visual
      auditory, sensorimotor-cortical, and interpeduncular systems. RBC spaces were not
      changed by nicotine treatment. RISA and blood spaces were increased slightly but
      not significantly in some of the LCBF-affected areas but nowhere else. Nicotine
      seemingly elevates LCBF in the affected areas mainly by increasing linear
      velocity of flow through the microvascular beds. In agreement with this, mean
      transit time, which is inversely related to velocity, was decreased from 0.3-0.5
      to approximately 0.2 s in the microvascular systems of the nicotine-affected
      areas.

PMID- 8285255
TI  - Inhibition of platelet aggregation and the stimulation of prostacyclin synthesis
      by insulin in humans.
AB  - An intravenous bolus injection of insulin (35.5 microM) followed by an infusion
      of insulin (0.53 microM.kg-1.h-1) for 2.5 h (which maintained plasma levels
      between 0.71 nM to 1.4 nM) in normal fasting volunteers (n = 16), increased
      [3H]prostaglandin E1 (a probe for prostacyclin) binding to platelets by two- to
      threefold over the control. Scatchard analyses showed that the increased binding
      was due to the increase of both high and low affinity receptor numbers with
      little change in the receptor affinities. Similar results were obtained by using
      [3H]prostacyclin as the radioligand. The increased binding was associated with
      more than a twofold decrease of the minimum concentration of prostanoid needed to
      inhibit aggregation of platelets through the increased formation of adenosine
      3',5'-cyclic monophosphate. Furthermore, the infusion increased the mean plasma
      prostacyclin level from 12.10 +/- 4.5 pM to 23.9 +/- 6.7 pM (n = 16; P < 0.001).
      These effects of insulin were at least partially direct, since the treatment of
      endothelial cells with insulin in tissue culture stimulated the production of the
      autacoid. Bolus injection of insulin (0.71 microM/kg) showed that the above
      effects of insulin could be demonstrated within 20 min after the injection,
      attained maximal ranges in approximately 60 min, and disappeared by 2-4 h.

PMID- 8285256
TI  - Endothelin-1 enhances cross-bridge function of ferret myocardium: role of second
      messengers.
AB  - To investigate postreceptor pathways of endothelin and the site of action
      responsible for enhancing myocardial contractility, studies were performed on
      ferret papillary muscles loaded with the Ca2+ indicator aequorin. Endothelin-1
      (ET) and the alpha 1-adrenoceptor agonist, phenylephrine (PE) produced similar
      dose-dependent increases in tension development and peak intracellular Ca2+
      concentration ([Ca2+]i); moreover, pretreatment with PE eliminated effects of ET,
      suggesting similar postreceptor pathways. Because alpha 1-adrenoceptor activation
      is thought to cause the hydrolysis of phosphatidylinositol and generate D-myo
      inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and 1,2-diacylglycerol (DAG), the
      protein kinase C (PKC) activator 4 beta-phorbol 12-myristate 13-acetate (PMA) was
      used to determine whether activation of PKC was responsible for the myocardial
      actions of ET. In contrast to ET, PMA decreased tension development and peak
      [Ca2+]i, and pretreatment with PMA attenuated the myocardial action of ET;
      however, intracellular Ins(1,4,5)P3 levels were greatly increased by ET
      stimulation, suggesting that rather than DAG, Ins(1,4,5)P3 might be the second
      messenger for the actions of ET. To determine whether ET produced actions on the
      contractile elements, thereby enhancing myocardial contractility, 2,3-butanedione
      monoxime (BDM) was used to interfere with the interaction of myosin and actin.
      Pretreatment with 6 mM BDM did not alter the half-maximum effective concentration
      (EC50) of the [Ca2+]o-tension relation, but, in contrast, shifted the ET dose
      response curve to the right, and increased the EC50 by approximately 1.0 log
      unit. In addition, ET partially reversed the downward shift of the peak [Ca2+]i
      peak tension curve induced by BDM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285257
TI  - Progressive loss of vasodilator responsive component of pulmonary hypertension in
      neonatal calves exposed to 4,570 m.
AB  - Severe neonatal pulmonary hypertension (PH) may have both reversible
      (vasoconstrictive) and "fixed" (vasodilator unresponsive) components. To assess
      when and to what degree vasodilator unresponsive PH developed in the neonate,
      pulmonary arterial pressures (PAP) and cardiac outputs (CO) were measured, and
      total pulmonary resistances (TPR) were calculated in neonatal calves exposed to
      chronic hypoxia (CH) (barometric pressure of 430 mmHg = 4,570 m) for 1, 3, 7, and
      14 days under both normoxic (barometric pressure of 640 mmHg = 1,500 m) and
      hypoxic conditions with and without an infusion of the vasodilator acetylcholine
      (ACh). Studies were done at 4 h and at 2, 4, 8, and 15 days of life in both
      control and CH animals. The fixed component of PH was defined as that PAP or TPR
      above the control baseline value which remained in CH animals after an infusion
      ACh at 1,500 m. Small pulmonary arteries were also examined histologically in an
      attempt to correlate relative changes in the reversible and fixed elements of PH
      with alterations in vessel structure. Chronic exposure to 4,570 m altitude
      prevented the normal postnatal fall in PAP and TPR observed in control animals.
      Instead, PAP, TPR, and the structure of small pulmonary arteries initially
      remained similar to those of the 4-h-old newborn. By 7 days exposure to 4,570 m,
      a significant element of fixed PH developed, which increased dramatically between
      the 7- and 14-day exposure periods and appeared to correlate with a narrowed
      pulmonary artery lumen and increased medial and adventitial thickness.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8285258
TI  - Metabolic inhibition enhances Ca(2+)-activated K+ current in smooth muscle cells
      of rabbit portal vein.
AB  - The effect of metabolic inhibition on macroscopic and single-channel K+ currents
      in isolated rabbit portal vein myocytes was investigated by patch-clamp
      technique. Depression of adenosine triphosphate synthesis was produced by 2-deoxy
      D-glucose (10 mM) and either cyanide (2 mM) or dinitrophenol (50 microM). Outward
      quasi-steady-state current evoked by a ramp protocol and outward time-dependent
      current during step depolarizations were increased during metabolic inhibition.
      The reversal potential for quasi-steady-state current shifted negatively toward
      equilibrium potential of K+ during treatment consistent with a role for K+
      conductance and hyperpolarization of membrane potential. The macroscopic K+
      current affected was 1) voltage dependent, 2) inhibited by intracellular Ca2+
      chelation and low tetraethylammonium ion (1 mM) but unaffected by 4-aminopyridine
      (2 mM), and 3) associated with a rise in intracellular Ca2+ assessed by indo 1.
      Metabolic inhibition caused an increase in voltage-dependent large-conductance K+
      channel (120-130 pS) activity in cell-attached patches of myocytes bathed in
      physiological solution (140 mM K+ in pipette). The channels were blocked in a
      flickery fashion by tetraethylammonium ion (0.5 mM) and inhibited with
      charybdotoxin (100 nM). We conclude that metabolic inhibition increases the
      activity of large-conductance Ca(2+)-activated K+ channels in vascular smooth
      muscle.

PMID- 8285259
TI  - A vascular transport operator.
AB  - A pulse or a sharp front in concentration of a tracer or a substrate in the blood
      within a vessel becomes dispersed while being transported along a vessel. Cross
      stream mixing and pulsations in flow with the heartbeat cause the dispersion to
      be less than would occur with a parabolic velocity profile (Newtonian flow).
      These characteristics allow intravascular mass transport to be described well by
      a simple two-parameter differential operator, which is a one-dimensional
      representation of the rather complex real situation. The operator consists of two
      components in series, a pure delay and a fourth-order linear differential
      operator. The latter is merely two underdamped second-order operators in series,
      with fixed relationships between the natural frequencies and damping
      coefficients. The operator is useful because it provides a transport function
      with skewness and kurtosis suitable to intravascular transport where the mean
      velocity profile is blunter than in Newtonian parabolic flow. The parameters of
      the operator are its mean transit time, t, and its relative dispersion, RD, which
      is the standard deviation of the response impulse divided by t. The operator
      transport function describes blood transport through the human leg arterial
      system, where the RD values are approximately 15-20%.

PMID- 8285260
TI  - Nitric oxide contributes to dilatation of cerebral arterioles during seizures.
AB  - Endogenous release of excitatory amino acids during seizures produces marked
      increases in neuronal activity and guanosine 3',5'-cyclic monophosphate levels in
      brain tissue, which are mediated by nitric oxide (NO). We tested the hypothesis
      that dilatation of the cerebral microcirculation during seizures is mediated by
      NO. Diameters of cerebral arterioles were measured using a closed cranial window
      in anesthetized rabbits. Three, five, nine, and eleven minutes after the onset of
      pentylenetetrazole-induced seizure (which releases endogenous excitatory amino
      acids), arteriolar diameter increased by 42 +/- 6, 30 +/- 3, 20 +/- 2, and 16 +/-
      2% (means +/- SE), respectively, from a control diameter of 86 +/- 6 microns.
      Arterial pressure was maintained at control levels during seizures. In the
      presence of NG-nitro-L-arginine (L-NNA, 300 microM), an inhibitor of NO synthase,
      vasodilatation during seizures was not affected at 3 min (40 +/- 8%) but was
      significantly reduced at 5, 9, and 11 min (17 +/- 5, 6 +/- 3, and 1 +/- 3%,
      respectively, P < 0.05 vs. control). Vasodilatation in response to topical
      application of acetylcholine (1 microM) was also inhibited by L-NNA (33 +/- 5 vs.
      3 +/- 2%, P < 0.05). Dilatation of cerebral arterioles in response to
      nitroprusside (1 and 10 microM) was not inhibited by L-NNA. Thus sustained, but
      not initial, dilatation of cerebral arterioles during seizures appears to be
      mediated in part by NO.

PMID- 8285261
TI  - Oral sensory stimulation in men: effects on insulin, C-peptide, and
      catecholamines.
AB  - To investigate the effect of oral sensory stimulation on cephalic phase insulin
      release (CPIR) and other compounds associated with glucose metabolism, a modified
      sham feed was used in which male subjects (n = 15) tasted, chewed, and then
      expectorated the food stimulus. Subjects remained fasted, sham fed, or ingested
      food on separate days over a 5-day period. After four baseline blood samples,
      poststimulus samples were taken every 2 min for 14 min and then every 15 min for
      2.25 h. Increases in plasma insulin and C-peptide were found during the cephalic
      phase time period (0-10 min poststimulus) on the sham-fed and fed conditions when
      compared with fasted values. Glucose, norepinephrine, epinephrine, and free fatty
      acids were not affected by oral sensory stimulation or food ingestion during the
      cephalic phase period. The magnitude and profile of CPIR were similar after sham
      feeding and food ingestion. This study demonstrates that oral sensory stimulation
      can elicit CPIR in humans independently of changes in blood glucose.

PMID- 8285262
TI  - Pancreatic glucagon suppresses gustatory responsiveness to glucose.
AB  - Peripheral administration of the gut peptide pancreatic glucagon (GGN) alters
      hepatic metabolism and suppresses feeding. Other physical (gastric distension)
      and chemical factors (hyperglycemia, hyperinsulinemia) that reduce food intake
      also suppress taste-evoked activity. This may attenuate the reinforcement derived
      from feeding and so promote termination of the meal. To determine whether this
      mechanism was operative with GGN administration, we studied the effect of hepatic
      portal infusions of 40 micrograms/kg pancreatic GGN on taste responses in the
      nucleus tractus solitarius of the rat. Taste activity was elicited by oral
      application of NaCl, glucose, HCl, and quinine HCl. Responses were monitored
      before and after injections of GGN or a control vehicle. Blood glucose levels
      were measured in separate groups of GGN- and vehicle-injected rats. Blood glucose
      increased significantly after GGN infusion and returned to control levels within
      35 min. Taste responsiveness to glucose was significantly reduced after the GGN
      injection and recovered to preinjection levels by 36 min. Activity evoked by
      NaCl, HCl, and quinine HCl was unaffected. The suppression of responsiveness to
      sugars may reduce the hedonic appeal of tastants and so serve as a mechanism by
      which GGN could contribute to postprandial satiety.

PMID- 8285263
TI  - Regulatory features of protein synthesis in isolated mitochondria from Artemia
      embryos.
AB  - Optimal conditions were developed for measuring rates of protein synthesis in
      isolated mitochondria from encysted embryos of Artemia franciscana to 1) identify
      the required chemical constituents, 2) assess the influence of extramitochondrial
      pH on protein synthesis, and 3) investigate potential mechanisms coordinating
      nuclear and mitochondrial gene expression. Isolation procedures resulted in
      intact, highly coupled mitochondria [respiratory control ratio = 6.48 +/- 0.43
      (SE), n = 21]. Requirements for maximal rates of protein synthesis, measured as
      incorporation of [3H]leucine (60 microM), included an oxidizable carbon source
      (10 mM succinate), adenine nucleotides (1.5 mM ADP), phosphate (10 mM), K+ (125
      mM), Mg2+ (10 mM), amino acids (0.3 mM of each), sucrose or trehalose (500 mM),
      EGTA (1 mM), and bovine serum albumin (1 mg/ml). Rates were linear for 60 min at
      25 degrees C (r = 0.99). Fluorography of translated products revealed 13
      peptides. Previous research has shown that anoxia-induced acidification of
      intracellular pH (pHi) results in suppression of protein biosynthesis, as judged
      by cytochrome-c oxidase synthesis. In the present study, mitochondrial protein
      synthesis was acutely sensitive to external pH, with 80% inhibition observed by
      lowering pH from 7.5 to 6.8. Thus acidification of pHi may serve as one
      intracellular signal contributing to a coordinated suppression of both
      cytoplasmic and mitochondrial protein synthesis during transitions from active to
      anoxia-induced quiescent states.

PMID- 8285264
TI  - Impairment of osmotically stimulated AVP release in patients with primary
      polydipsia.
AB  - The secretion of arginine vasopressin (AVP) from the posterior pituitary is
      primarily and finely regulated by the osmolality of plasma. Even though a number
      of factors alter osmolality-induced release of AVP, there are no published data
      in humans that have addressed the role of chronic overhydration on this
      phenomenon. To address this problem we have identified eight patients with
      primary polydipsia using criteria not involving measurement of AVP, and have
      subjected them to standardized infusions of hypertonic saline. These patients had
      less AVP in both plasma and urine in relation to plasma osmolality than was found
      in normal subjects. In addition, their rate of rise of plasma and urine AVP was
      less than in normal subjects. Their osmotic threshold for AVP release may have
      been higher than normal. These data demonstrate that chronic overhydration in
      humans downregulates the release of AVP in response to hypertonicity. This
      phenomenon may explain the impairment of urine concentration in patients with
      primary polydipsia and emphasizes the basis of the difficulty that may occur
      clinically in differentiating between patients with primary polydipsia and
      partial central diabetes insipidus.

PMID- 8285265
TI  - Basic fibroblast growth factor may mediate proliferation in the compensatory
      adrenal growth response.
AB  - We have investigated the role of basic fibroblast growth factor (bFGF) in the
      neurally mediated compensatory adrenal growth response. Unilateral adrenalectomy
      resulted in a 13, 6, and 22% increase in adrenal weight, protein, and DNA
      content, respectively, and 33-40% increases in the rate of cell proliferation
      measured by [3H]thymidine incorporation in vitro. Three forms of bFGF,
      approximately 18.6, 21, and 22.5 kDa, were identified in rat adrenals by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. bFGF was
      localized immunocytochemically in cells of the glomerulosa and the medulla. bFGF
      stimulated a 68-80% increase in the rate of DNA synthesis in adrenal capsule
      glomerulosa preparations in vitro. Suramin (0.1 mM), a growth factor antagonist,
      blocked bFGF receptor interaction in vitro and, at 200 mg/kg given 5-7 days
      before adrenal surgery, blocked compensatory growth. Conversely, at 2.0 mg/kg,
      suramin significantly enhanced the compensatory growth response, perhaps caused
      by suramin-induced bFGF receptor upregulation, since suramin pretreatment also
      enhanced DNA synthesis in response to exogenous bFGF in vitro. These results
      suggest that bFGF may mediate proliferation in the compensatory adrenal growth
      response.

PMID- 8285266
TI  - Cerebral metabolism and electrocortical activity in the chronically hyperglycemic
      fetal lamb.
AB  - Previous studies in the fetal lamb have demonstrated that hyperglycemia
      stimulates the fetal metabolic rate. The present study examined the effects of
      chronic fetal hyperglycemia on fetal cerebral metabolic rate and electrocortical
      activity. Nine chronically instrumented fetal lambs had measurements of cerebral
      blood flow and cerebral uptake/excretion of oxygen, glucose, lactate, and beta
      hydroxybutyrate taken before and during a 48-h fetal glucose infusion.
      Electrocortical activity was also recorded. The fetal arterial glucose
      concentration was 19.8 +/- 2.0 mg/dl before glucose infusion and 48 +/- 4.5 to
      54.6 +/- 6.6 mg/dl during the infusion period. Cerebral blood flow and cerebral
      glucose and oxygen uptake increased by 219, 209, and 171%, respectively, by the
      end of the infusion period. There was a linear relationship between the fetal
      arterial glucose concentration and cerebral blood flow and cerebral glucose and
      oxygen uptakes. The electroencephalogram showed significant slowing with
      increases in the cerebral metabolic rate. These findings suggest that fetal
      hyperglycemia is associated with significant metabolic stimulation of the brain.

PMID- 8285267
TI  - Angiotensin II: nitric oxide interaction and the distribution of blood flow.
AB  - Nitric oxide (NO) contributes to the regulation of regional blood flow.
      Inhibition of NO synthesis increases blood pressure and vascular resistance.
      Using radioactive microspheres and the substrate antagonist N omega-nitro-L
      arginine methyl ester (L-NAME) (10 mg/kg) to block NO synthesis, we tested the
      hypothesis that there is a significant interaction between the vasodilator NO and
      the vasoconstrictor angiotensin II, which regulates regional hemodynamics.
      Further, we investigated the influence of anesthesia on this interaction. L-NAME
      increased blood pressure, decreased cardiac output, and increased total
      peripheral resistance in both anesthetized and conscious rats. In anesthetized
      rats, L-NAME decreased blood flow to visceral organs (i.e. kidney, intestine, and
      lung) but had little effect on blood flow to the brain, heart, or hindlimb.
      Treating anesthetized rats with the angiotensin II receptor antagonist losartan
      (10 mg/kg) attenuated the decrease in cardiac output and the increase in total
      peripheral resistance without affecting the pressor response to L-NAME. Losartan
      also attenuated the visceral hemodynamic responses to L-NAME. In conscious rats,
      L-NAME decreased blood flow to all organ beds. Treating these rats with losartan
      only marginally attenuated the increase in total peripheral resistance to L-NAME
      without significantly affecting the pressor response or the decrease in cardiac
      output. Losartan had no effect on the regional hemodynamic responses to L-NAME.
      These data suggest that NO-mediated vascular relaxation is an important regulator
      of total peripheral and organ vascular resistance. (ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8285268
TI  - Sex difference in the antidiuretic activity of vasopressin in the rat.
AB  - A possible gender difference in the antidiuretic activity of vasopressin was
      studied in male and female Sprague-Dawley rats. Infusion of vasopressin (3-100
      pg.kg-1.min) into conscious, chronically instrumented water-loaded rats resulted
      in a dose-dependent antidiuresis in both male and female rats. Male rats,
      however, were more than three times more sensitive to vasopressin than female
      rats. Thus the effective doses of vasopressin (pg.kg-1.min-1) to decrease urine
      flow to 30 microliters.min-1.100 g-1 (18 +/- 5 in males; 58 +/- 12 in females),
      to increase urine osmolality to 600 mosmol/kgH2O (35 +/- 5 in males; 119 +/- 15
      in females), and to decrease free water clearance to 30 microliters.min-1.100 g-1
      (8 +/- 3 in males; 28 +/- 7 in females) were significantly (P < 0.05) lower in
      males. Furthermore, in vitro studies in papillary collecting duct cells
      demonstrated a significantly higher density of vasopressin V2 receptors and a
      greater ability of vasopressin to stimulate adenosine 3',5'-cyclic monophosphate
      (cAMP) accumulation in males than in females. Vasopressin V2-receptor density
      (maximum binding) was 359 +/- 47 and 238 +/- 22 fmol/mg in male and female rats,
      respectively (P < 0.05). There was no difference in apparent dissociation
      constants (Kd). Vasopressin resulted in a dose-dependent increase in cAMP
      accumulation in papillary collecting duct cells, and at the highest concentration
      of vasopressin used (10(-8) M) cAMP increased from 44 +/- 10 to 182 +/- 51
      fmol/micrograms protein in males and from 30 +/- 4 to 91 +/- 18 fmol/micrograms
      protein in females (P < 0.05). (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285269
TI  - Tonic descending modulation of spinal neuronal responses to activation of renal
      receptors.
AB  - Experiments were conducted in anesthetized cats to determine if spinal neuronal
      responses to activation of renal receptors are tonically modulated by descending
      spinal pathways. Eighty-seven thoracolumbar spinal neurons with renal and somatic
      input were tested for responses to occlusion of the renal vein, renal artery, and
      ureter before, during, and after cooling the spinal cord rostral to the recording
      site. Cooling increased the number of neurons that responded as well as the
      magnitude of the responses to renal vein (RVO), renal artery (RAO), and ureteral
      occlusion (UO). RVO increased cell activity of 21 neurons from 12.5 +/- 2.7 to
      31.7 +/- 6.0 spikes/s during cooling. UO increased cell activity of 24 neurons
      from 9.0 +/- 2.1 before cooling to 25.0 +/- 4.9 spikes/s during cooling. Cold
      block increased the magnitude of both types of responses to RAO that were due to
      mechanical deformation of the renal artery and prolonged renal ischemia. These
      data show that the majority of spinal neuronal responses to renal receptor
      stimulation are modulated by tonic inhibitory influences. Thus these results
      provide a mechanism by which the brain may control spinal circuitry that
      underlies reflexes of renal origin.

PMID- 8285270
TI  - Psychoneuroendocrine profile associated with hypertension or hyperactivity in
      spontaneously hypertensive rats.
AB  - The behavioral and neuroendocrine reactivity to a novel environment (open field)
      and the adrenocorticotropic hormone (ACTH)/corticosterone response to a
      corticotropin-releasing factor (CRF) challenge were measured in 2-mo-old rats
      from four inbred strains derived from the Wistar-Kyoto rat: spontaneously
      hypertensive rats (SHRs), hypertensive and behaviorally hyperactive to novelty;
      WKY, neither hypertensive nor hyperactive; WKHA, hyperactive but normotensive;
      and WKHT, only hypertensive. The ACTH response to CRF was much lower in SHRs than
      WKYs, this reduced reactivity being clearly associated with the hyperactivity
      trait, since it was present in the WKHA and absent in the WKHT strain. On the
      other hand, the ACTH/corticosterone response to a psychological stimulus (open
      field) could not clearly discriminate the four strains. The largest difference
      was found in the prolactin response. Post-open-field levels were much lower in
      the WKHA (27.11 +/- 4.69 ng/ml) than in the parent WKY strain (83.65 +/- 6.84
      ng/ml), the hypertensive strains having intermediate levels (WKHT: 58.05 +/- 7.65
      ng/ml; SHR: 64.13 +/- 7.19 ng/ml). Other differences were also found in the
      levels of aldosterone and renin activity. These results indicate that these
      strains are an excellent model to study neuroendocrine correlates of hypertension
      and hyperactivity, which are associated in the SHR strain and may be of interest
      for the study of the association between neuroendocrine and behavioral
      characteristics.

PMID- 8285271
TI  - Coronary vasoconstrictor pathway from anterior hypothalamus includes neurons in
      RVLM.
AB  - We have previously identified discrete brain sites [anterior (AHA) and lateral
      hypothalamus, periaqueductal gray, pontine parabrachial nucleus, lateral
      reticular formation, and rostral ventrolateral medulla (RVLM)] in the cat, in
      which electrical or chemical activation produces coronary vasoconstriction. This
      study examines whether the most rostral (AHA) and caudal (RVLM) of these sites
      are connected as part of a common pathway mediating coronary vasoconstriction. In
      chloralose-anesthetized cats, electrical stimulation in the AHA produced maximum
      increases in arterial pressure (41 +/- 10%) and coronary vascular resistance (28
      +/- 9%). Microinjection of lidocaine into the RVLM attenuated the increases in
      arterial pressure (10 +/- 3%) and coronary vascular resistance (5 +/- 1%) in
      response to electrical stimulation in the AHA (P < 0.05 vs. before lidocaine).
      Lidocaine nonspecifically inhibits neural elements in the region. gamma
      Aminobutyric acid in the RVLM, which selectively inhibits cell bodies and not
      fibers passing through the RVLM, attenuated the increase in coronary vascular
      resistance (38 +/- 8 to 14 +/- 3%; P < 0.05) but not the increase in arterial
      pressure (87 +/- 12 to 92 +/- 16%) in response to electrical stimulation in the
      AHA. These data indicate that coronary vasoconstriction in response to electrical
      stimulation in the AHA requires cell bodies in the RVLM; however, the associated
      pressor response is mediated by fibers passing through the RVLM. We conclude that
      a polysynaptic descending pathway that mediates sympathetic coronary
      vasoconstriction descends from the AHA through a synaptic connection in the RVLM.

PMID- 8285272
TI  - Effect of plasma osmolality on steady-state fluid shifts in perfused cat skeletal
      muscle.
AB  - Fluid redistribution in isolated perfused cat calf muscle caused by rapid
      increases in plasma osmolality was studied using NaCl or sucrose. Extracellular
      tracers (51Cr-labeled EDTA or [3H]mannitol) were added to the perfusate 90 min
      before solutes were added, and samples were taken from plasma immediately before
      osmolality was increased and 17, 40, and 65 min later. Interstitial fluid volume
      (IFV) was calculated as extracellular volume (ECV) minus plasma volume (Evans
      blue dye). Total tissue water changes (delta TTW) were measured by continuous
      recording of tissue weight. Change in intracellular volume (delta ICV) was
      obtained from delta TTW--delta IFV. TTW, IFV, ICV, and plasma osmolality were in
      steady state after 17 min. Changes in hydrostatic and colloid osmotic pressure
      were insignificant in comparison with small-molecule osmotic pressure changes.
      The apparent volume of TTW participating in the fluid shift averaged 65 +/- 1
      ml/100 g (SE) over a wide range of osmolality increases. In contrast to the large
      changes in TTW, IFV was not altered by osmolality. Thus decreases in TTW were
      similar to cell dehydration. Hence, increases in plasma volume induced by
      hypertonic fluids may come entirely at the expense of cell volume, not
      interstitial volume.

PMID- 8285273
TI  - Dehydration tolerance in wood frogs: a new perspective on development of
      amphibian freeze tolerance.
AB  - Wood frogs, Rana sylvatica, tolerate the loss of 50-60% of total body water
      during experimental dehydration. The rate of water loss for unprotected frogs is
      the same whether animals are frozen (at -2 degrees C) or unfrozen (at 1 degrees
      C) but is greatly reduced when frogs are frozen under a protective layer of moss.
      Dehydrational death could occur in as little as 7-9 days for unprotected animals;
      this indicates the importance for winter survival of selecting well-protected and
      damp hibernation sites. Prior dehydration affected the cooling and freezing
      properties of frogs, reducing supercooling point and the amount of ice formed
      after 24 h at -2 degrees C and acting synergistically with freezing exposure in
      stimulating cryoprotectant synthesis. Analysis of the effects of controlled
      dehydration at 5 degrees C showed that changes in body water content alone
      (without freezing) stimulated liver glycogenolysis and the export of high
      concentrations of glucose into blood and other organs. Autumn-collected frogs
      dehydrated to 50% of total body water lost showed glucose levels of 165-1,409
      nmol/mg protein in different organs, increases of 9- to 313-fold compared with
      control values and reaching final levels very similar to those induced by
      freezing exposure. The data support the proposal that various adaptations for
      natural freeze tolerance may have been derived from preexisting mechanisms for
      dealing with water stress in amphibians and that cell volume change may be one of
      the signals involved in triggering and sustaining molecular adaptations (e.g.,
      cryoprotectant output) that support freezing survival.

PMID- 8285274
TI  - Effects of glucose infusion on hormone secretion and hepatic glucose production
      during heavy exercise.
AB  - Blood-borne metabolic feedback vs. neural feedforward regulation of glucose
      homeostasis during exercise was investigated by infusion glucose and [3H]glucose
      for glucose appearance determination intravenously in rats running for 20 min at
      28 m/min [approximately 85% of maximal O2 consumption (VO2max)]. Infused glucose
      corresponded to the exercise-induced increase in hepatic glucose production (HGP)
      found in saline-infused rats. Saline- and glucose-infused resting rats were also
      studied. Arterial blood was sampled for analyses of hormones and metabolites.
      Plasma epinephrine, norepinephrine, and insulin were always similar and HGP was
      initially similar in the two exercising groups, although glucose infusion
      resulted in higher plasma glucose compared with control (P < 0.05). Late during
      exercise, high plasma glucose (11.3 +/- 0.4 vs. 9.6 +/- 0.3 mM) and low glucagon
      (16 +/- 2 vs. 27 +/- 3 pM) in glucose- vs. saline-infused rats caused an
      inhibition of HGP in glucose-infused rats, although never below preexercise
      levels. In resting rats, glucose infusion resulted in elevated plasma glucose and
      insulin and, in turn, inhibition of HGP but had no effect on catecholamines,
      corticosterone, or glucagon. The findings indicate that during heavy exercise,
      glucose homeostasis is regulated primarily by neural feedforward mechanisms and
      that blood-borne metabolic feedback mechanisms play a regulatory role if
      metabolic error signals are pronounced.

PMID- 8285275
TI  - Interaction between temperature and hypoxia in the alligator.
AB  - Hypoxia elicits behavioral hypothermia in alligators. Under normoxic conditions,
      the selected body temperature is 27.8 +/- 1.2 degrees C. However, when inspired
      O2 is lowered to 4%, selected body temperature decreases to 15.4 +/- 1.0 degrees
      C. The threshold for the behavioral hypothermia is between 4 and 5% inspired O2,
      the lowest threshold measured so far in terrestrial vertebrates. This study
      assessed the physiological significance of the behavioral hypothermia. The body
      temperature was clamped at 15, 25, and 35 degrees C for measurements of
      ventilation, blood gases, metabolic rate, plasma lactate, and acid-base status.
      Hypoxia-induced changes in ventilation, acid-base status, oxygen consumption, and
      lactate were proportional to body temperature, being pronounced at 35 degrees C,
      less at 25 degrees C, and absent at 15 degrees C. The correlation between
      selected body temperature under severe hypoxia and the measured parameters show
      that behavioral hypothermia is a beneficial response to hypoxia in alligators.

PMID- 8285276
TI  - Acute exercise and skeletal muscle antioxidant and metabolic enzymes: effects of
      fiber type and age.
AB  - Inhibition of metabolic enzyme activity has been associated with free radical
      stress in locomotor muscle with prolonged or intense exercise. However, it is not
      known whether such alterations with acute exercise in skeletal muscle are
      influenced by muscle fiber type or age. Twenty 4-mo-old and twenty 24-mo-old
      female Fischer-344 rats were divided at random into young exercised (YE; n = 10),
      old exercised (OE; n = 10), young control (YC; n = 10), and old control (OC; n =
      10) groups. Animals in both YE and OE groups ran on a treadmill (10% uphill
      grade) for 40 min at approximately 75% of each age-group's maximal O2
      consumption. Immediately after the treadmill run, white gastrocnemius (WG), red
      gastrocnemius (RG), and soleus (SOL) muscles were removed and quick-frozen in
      liquid nitrogen. Malondialdehyde was significantly increased (P < 0.05) in RG of
      YE vs. YC rats. Glutathione peroxidase activity was significantly elevated (P <
      0.05) in the WG of YE rats. Analysis of variance revealed a significant over-all
      increase in superoxide dismutase activity with exercise. Activities of
      phosphofructokinase (PFK), citrate synthase, succinate dehydrogenase, and 3
      hydroxyacyl-CoA dehydrogenase were unchanged (P > 0.05) with acute exercise in
      the SOL. However, PFK activity was decreased in the WG by 60% in OE but only 33%
      in YE, and in the RG by 41% in OE but only 21% in YE. We conclude that maximal
      glycolytic flux in the gastrocnemius may be adversely affected by acute exercise,
      and this effect was more pronounced in the 24-mo-old group.

PMID- 8285277
TI  - Tumor necrosis factor is not involved in exercise-induced elevation in core
      temperature.
AB  - Female Sprague-Dawley rats (12:12-h light-dark photoperiod) with access to
      running wheels have an elevated body temperature (BT) both during exercise
      (nighttime) and nonexercise periods (daytime). We studied whether the exercise
      induced increase in BT is modulated by the release of the cytokine, tumor
      necrosis factor-alpha (TNF). Two weeks after the onset of exercise, nighttime
      temperatures of exercising rats were elevated approximately 0.5 degree C compared
      with preexercise values (P = 0.006). By 3 wk after the onset of exercise, daytime
      temperatures had increased 0.3 degree C (P = 0.03) above control levels. To
      confirm that endogenously produced TNF can modulate fever in female rats, we
      injected six rats with antiserum to TNF (300 microliters/rat) and six rats with
      control serum 24 h before intraperitoneal injection of lipopolysaccharide (50
      micrograms/kg). As occurred in earlier studies on male rats, antiserum-treated
      female rats had significantly enhanced fevers (P = 0.017). To determine whether
      endogenously produced TNF was involved in modulating the daytime and nighttime
      increases in BT, antiserum to TNF (300 microliters/rat, n = 7) or control serum
      (300 microliters/rat, n = 5) was injected intraperitoneally in exercising rats.
      Neither injection of antiserum nor control serum had any effect on daytime or
      nighttime BTs. Because BTs of exercising female rats injected with antiserum
      against TNF were not affected, we conclude that TNF is not responsible for
      modulating their exercise-induced rise in BT.

PMID- 8285278
TI  - NTS neuronal responses to arterial pressure and pressure changes in the rat.
AB  - Central representation of arterial pressure by baroreceptor target neurons in the
      nucleus of the solitary tract (NTS) has not been studied. The present experiments
      sought to characterize response patterns of NTS baroreceptive cells in
      anesthetized, paralyzed, and artificially ventilated rats to both resting
      pressures and induced blood pressure challenges. Single-unit extracellular
      recordings were made from 83 baroreceptive NTS cells that received a synaptic
      input after electrical stimulation of the aortic nerve [latency, 2.46 +/- 0.78
      (+/- SD) ms] and were located at an anatomically defined region known to receive
      baroreceptor afferents. Seventy-one neurons were presumed second order, since
      they received a short (< 5 ms) and invariant (< +/- 0.5 ms) synaptic input from
      the ipsilateral aortic nerve. Thirty-five of these neurons were silent at resting
      blood pressures and produced few (1-4) spikes when presented with induced pressor
      responses. The remainder (n = 36) had ongoing activity that was not pulse
      rhythmic and that varied in rate nonuniformly with arterial blood pressure during
      an induced challenge. Ongoing activity was analyzed for active neurons, revealing
      both R wave-related and lung inflation-related phasic activity. The present data
      suggest that baroreceptive NTS neurons may be sensitive to many characteristics
      of the input signal, such as dP/dt, mean pressure, and cardiac frequency, as well
      as pulmonary afferent drive.

PMID- 8285279
TI  - Role of intrapreoptic norepinephrine in endotoxin-induced fever in guinea pigs.
AB  - The peripheral administration of pyrogens has been shown previously to affect the
      activity of central noradrenergic neurons, but the effects have been variable and
      no consensus has emerged regarding their functional significance. Because
      norepinephrine (NE) microdialyzed into the preoptic area (PO) of the anterior
      hypothalamus of conscious guinea pigs is hypothermizing, the possibility was
      investigated whether NE might be a febrilytic rather than a febrigenic mediator.
      Intravenous injections of Salmonella enteritidis lipopolysaccharide (2.0
      micrograms/kg) evoked a bimodal fever, which was attenuated in a dose-dependent
      manner by NE microdialyzed (10 or 20 micrograms/microliters at a rate of 2
      microliters/min for various durations) into the PO. The alpha 2-adrenergic
      receptor antagonists rauwolscine (1 or 2 micrograms/microliters) and yohimbine (1
      microgram/microliter) microdialyzed intrapreoptically significantly reduced the
      trough of body (core) temperature (Tc) between the first and second peaks of the
      bimodal fever and prolonged the overall febrile course. None of these effects was
      associated with changes in skin temperature. The level of NE (assayed by high
      performance liquid chromatography with electrochemical detection) in the preoptic
      extracellular fluid collected by intracerebral microdialysis was significantly
      elevated at the end of each rising phase of the bimodal fever, just before or
      about the time when Tc began to fall, compared with pyrogen-free saline controls
      at the same times. These results suggest that intrapreoptic NE may have a
      thermolytic effect on fever by reducing metabolic heat production and may thus
      play a physiological role in the initiation of febrilysis in guinea pigs.

PMID- 8285280
TI  - De novo protein synthesis and protein phosphorylation during anoxia and recovery
      in the red-eared turtle.
AB  - Changes in de novo protein synthesis and protein phosphorylation were monitored
      during anoxia and recovery in the red-eared slider Trachemys (= Pseudemys)
      scripta elegans. Time courses of 35S-radiolabeled methionine incorporation into
      acid-precipitable material showed an increase up to 5 h postinjection and
      remained constant after this time. Comparison of the total and acid-precipitable
      35S label incorporation into tissues from 20-h control, anoxic, and recovering
      animals showed differences between these groups: total radioactivity in brain was
      2.9-fold lower in recovering turtles, whereas protein-associated radioactivity
      was 2.4-fold higher in anoxic liver, 2.3-fold lower in recovering skeletal
      muscle, and 3.7-fold lower in recovering brain tissue. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of radiolabeled proteins showed the existence
      of a newly synthesized protein band (relative molecular mass = 72 kDa) that was
      apparent only in 20-h recovering liver and skeletal muscle. Use of 32P labeling
      to monitor changes in protein phosphorylation patterns during anoxia revealed 1.6
      , 1.4-, and 1.5-fold increases in 32P incorporation in anoxic brain, heart, and
      liver, respectively. Changes in protein phosphorylation were localized to the
      plasma membrane and cytosolic fractions in brain and to the cytosolic fraction in
      liver.

PMID- 8285281
TI  - Parenteral nutrition, brain glycogen, and food intake.
AB  - To determine whether brain glycogen concentrations change during parenteral
      nutrition, Fischer 344 rats with jugular vein catheters received 0.9 N saline or
      parenteral nutrition providing 100% of daily calories (PN-100). Rats were killed
      after 4 days of PN-100 and serially after PN-100 was stopped. Food intake
      decreased during PN-100 to approximately 15% of control, but total kilocalories
      eaten and infused over the 4-day PN-100 period was approximately 130% of control.
      Food intake of PN-100 rats remained low for 3-4 days post-PN-100. At the end of
      the 4-day PN-100 period, plasma glucose and insulin (P = 0.01) and whole brain
      glycogen (P < 0.005) were higher than but similar to control within 24 h of PN
      100 being stopped. When PN-100 rats were not allowed to eat during the infusion
      period, plasma glucose was lower, plasma insulin higher, and brain glycogen
      content the same as in control rats after 4 days of PN-100. The increased brain
      glycogen was the likely consequence of the hyperglycemia and hyperinsulinemia
      during PN-100 and was not causally associated with the reduced food intake either
      during or immediately after PN-100.

PMID- 8285282
TI  - ICI 182,780: a pure antiestrogen that affects behaviors and energy balance in
      rats without acting in the brain.
AB  - ICI 182,780 is one of a new class of steroidal antiestrogens that differs from
      nonsteroidal antiestrogens, such as tamoxifen, in a number of respects. 1) It is
      bound by estrogen receptors with a high affinity, similar to that for estradiol.
      2) It is a "pure" antiestrogen in that it does not mimic any of the effects of
      estradiol. 3) This class of antiestrogens does not seem to be bound by
      antiestrogen binding sites. 4) ICI 182,780 may not be active in the brain after
      peripheral administration. Indeed, ICI 182,780 blocked in vivo cell nuclear
      binding of [3H]estradiol in uterus, pituitary, and adipose tissue but not in
      hypothalamus-preoptic area. In vitro, ICI 182,780 competed for binding by neural
      estrogen receptors with an affinity comparable with that for estradiol. When
      given to ovariectomized rats, ICI 182,780 did not mimic any of the actions of
      estradiol. Instead, ICI 182,780 treatment completely blocked the uterotrophic
      effects of estradiol and attenuated the actions of estradiol on linear growth,
      carcass fat content, fat pad weight, and sexual receptivity. Treatment with ICI
      182,780 also attenuated the estrogenic effects of tamoxifen on food intake, body
      weight and composition, linear growth, and uterine weight. These findings support
      the concept that, in addition to its actions in the brain, estradiol can act
      peripherally to modulate regulatory behaviors, energy balance, and estrous
      behavior. They are also consistent with the hypothesis that nonsteroidal
      antiestrogens, such as tamoxifen, affect energy balance via estrogen receptors,
      rather than antiestrogen binding sites.

PMID- 8285283
TI  - ICI 182,780 antagonizes the effects of estradiol on estrous behavior and energy
      balance in Syrian hamsters.
AB  - Three experiments examined the effects of ICI 182,780, a steroidal "pure"
      antiestrogen that is thought to be active peripherally but not in the brain when
      given systemically, on energy balance, estrous behavior, and in vivo cell nuclear
      binding of [3H]estradiol in Syrian hamsters. Pretreatment with ICI 182,780
      reduced in vivo uptake of [3H]estradiol in uterus but not in pooled hypothalamus
      preoptic area. Ovariectomized Syrian hamsters were treated with estradiol
      benzoate (EB, 5 micrograms/day), ICI 182,780 (250 micrograms/day), or both EB and
      ICI 182,780 for 4 wk. Estradiol treatment caused significant decreases in food
      intake, body weight and fat content, and linear growth. Given alone, ICI 182,780
      had no effect on these measures. When they were given concurrently, ICI 182,780
      attenuated the effects of estradiol on body weight, growth, and fat content but
      not on food intake. Treatment with ICI 182,780 significantly diminished estrous
      behavior induced with either EB plus progesterone or with EB alone. These
      findings support the hypothesis that, in addition to its actions in the brain,
      estradiol acts peripherally to modulate estrous behavior and energy balance.

PMID- 8285284
TI  - Role of olfaction in starch and oil preference.
AB  - Two different techniques were used to assess the role of olfaction in the
      preference rats show for dilute nutrient suspensions and solutions. Removal of
      the olfactory bulbs reduced but did not abolish preference for 1% starch and oil
      emulsions. Removal of the olfactory bulbs also reduced preference for sucrose,
      Polycose, and saccharin. In another experiment, rats were rendered anosmic with
      intranasal zinc sulfate. The degree of anosmia was evaluated by measuring
      preference for an aqueous solution of citral and vanillin. Rats whose avoidance
      of citral plus vanillin had been abolished by zinc sulfate continued to prefer a
      1% starch suspension over vehicle, although starch preference was significantly
      reduced. It is concluded that starch and oil preference is mediated by both
      olfactory and nonolfactory cues.

PMID- 8285285
TI  - Role of NO in goat basal cerebral circulation and after vasodilatation to
      hypercapnia or brief ischemias.
AB  - The role of nitric oxide (NO) in the cerebral circulation under basal conditions
      and after vasodilatation to hypercapnia or reactive hyperemias was studied in 17
      anesthetized goats. The intravenous administration of NG-nitro-L-arginine methyl
      ester (L-NAME, 3-4 or 8-10 mg/kg), an inhibitor of nitric oxide production,
      reduced middle cerebral artery (MCA) flow (electromagnetically measured) by 19
      and 30% and increased systemic arterial pressure by 21 and 26%, respectively,
      whereas heart rate did not significantly change; MCA resistance increased by 48
      and 86%, respectively. These hemodynamic effects were reversed by L-arginine (200
      300 mg/kg iv; 5 goats). Different levels of hypercapnia (PCO2 of 30-35, 40-45,
      and 55-65 mmHg) (12 goats) produced arterial PCO2-dependent increases in MCA flow
      that were similar under control and L-NAME treatment. Graded cerebral hyperemia
      occurred after 5, 10, and 20 s of MCA occlusion in 5 goats, but its magnitude was
      decreased during L-NAME treatment. It suggests that, in the cerebral circulation,
      nitric oxide 1) produces a basal vasodilator tone and 2) is probably not involved
      in the vasodilatation to hypercapnia but may mediate hyperemic responses after
      short brain ischemias.

PMID- 8285286
TI  - Biological actions of brain natriuretic peptide in thoracic inferior vena caval
      constriction.
AB  - Brain natriuretic peptide (BNP) shares structural and functional similarities to
      atrial natriuretic peptide (ANP). Although BNP and ANP interact with the same
      biologically active guanylate cyclase-coupled receptor, recent reports conflict
      with regard to the biological actions of exogenous BNP in sodium-retaining and
      edematous states. We studied the biological actions of BNP in normal dogs (n = 5)
      and sodium-avid dogs with chronic thoracic inferior vena caval constriction
      (TIVCC) (n = 6). In normal dogs BNP increased glomerular filtration rate, renal
      blood flow, and urinary sodium excretion and decreased proximal and distal
      fractional reabsorption of sodium with activation of urinary guanosine 3',5'
      cyclic monophosphate (cGMP). These renal actions occurred in association with
      marked hypotensive actions and activation of systemic cGMP. In TIVCC, a state
      characterized by chronic reductions of cardiac output, avid sodium retention,
      edema, and activation of the renin-angiotensin-aldosterone system (RAAS), the
      renal actions of BNP were absent in association with marked attenuation of the
      urinary cGMP response. In contrast, an enhanced hypotensive response with
      preserved activation of systemic cGMP was observed. In neither normal dogs nor
      TIVCC dogs did BNP inhibit the RAAS. These studies report that BNP is a potent
      vasoactive and natriuretic peptide with potent proximal and distal tubular
      actions in normal dogs. These studies also demonstrate that in TIVCC, a model of
      low cardiac output and congestive failure that results in marked sodium retention
      with edema in which there is activation of the RAAS, the renal actions of BNP are
      attenuated while the vasoactive actions are enhanced.

PMID- 8285287
TI  - Adaptations of myocardial beta-adrenergic receptor complex in hibernating
      marmots.
AB  - Properties of marmot (Marmota flaviventris) myocardial beta-adrenergic receptor
      complex (beta-AR) were evaluated during hibernation (H), in summer (S) animals,
      and in animals aroused from hibernation (C). The results obtained for S and C
      animals were identical, and only the results for C animals are shown. In H-animal
      myocardial membrane preparations assayed at 37 degrees C, isoproterenol-dependent
      adenylate cyclase activity (ACA) was consistently higher, whereas the synergistic
      contribution of 5'-guanylylimidodiphosphate [Gpp(NH)p] in this reaction was
      reduced. When assayed at 10 degrees C, only the ACA in H animals responded to the
      combination of isoproterenol and Gpp(NH)p. In contrast, at 10 degrees C, ACA in
      response to Gpp(NH)p alone is essentially equal in H and C animals. Hibernation
      did not change myocardial beta-AR receptor density or affinity. In contrast,
      analysis of isoproterenol displacement of [125I]iodocyanopindolol revealed that
      the proportion of beta-AR in the high-affinity state was substantially greater in
      H than in C animals, and this relationship was retained even in the presence of
      Gpp-(NH)p. In an evaluation of the role of the GTP binding proteins that couple
      the beta-AR to the effector adenyl cyclase, we determined that there was no
      change in the cholera toxin- or pertussis toxin-dependent ADP ribosylation
      patterns. Immunochemical detection of the individual GTP binding proteins
      revealed no change in the levels of G alpha i1, G alpha i2, or G alpha i3. In
      contrast, we observed a hibernation-associated decrease in G alpha o associated
      with the plasma membrane-enriched particulate fraction. (ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8285288
TI  - Synchrony between breathing and shivering in three muscles of bantam hens exposed
      to cold eggs.
AB  - Unrestrained, incubating bantam hens (Gallus domesticus) were exposed to cold,
      water-perfused eggs to induce shivering. Mean rectified electromyogram (EMG
      activity) was recorded from the iliotibialis, gastrocnemius, and pectoralis
      muscles, together with breathing and O2 consumption. EMG activity in all three
      muscles varied in synchrony with breathing, as confirmed by spectral analysis.
      The highest shivering intensity occurred during end expiration. This synchrony
      was also present when respiratory frequency was increased by hypercapnic/hypoxic
      stimuli and tended to improve with increasing respiratory frequency and tidal
      volume. The absolute modulation of shivering intensity remained relatively
      constant with increasing average intensity, indicating that breathing-modulated
      motor units are activated first. In the less active pectoralis muscle, all
      activity was modulated. Modulation is probably not restricted to one type of
      muscle fiber because it occurs in both predominantly red hindquarter muscles and
      the white pectoralis muscle. It is tentatively suggested that respiratory drive
      related influence from the brain stem has a synchronizing effect on spinal cord
      activity. A bursting activity pattern may be more favorable for muscle
      circulation than a tonic discharge pattern.

PMID- 8285289
TI  - Hyperthermia protects mice against the lethal effects of endotoxin.
AB  - Recently, investigators have reported that heat shock proteins (HSPs) can protect
      isolated cells from cytotoxicity induced by two important mediators of sepsis:
      interleukin-1 and tumor necrosis factor. The present study was undertaken to
      examine the hypothesis that transient whole body hyperthermia could decrease
      mortality from subsequent challenge with gram-negative endotoxin. We demonstrate
      that heat pretreatments improved long-term survival fivefold in a mouse endotoxin
      model and this was correlated with the production of HSPs. There was a marked
      difference in individual organ expression of the inducible 72-kDa heat shock
      protein (HSP72). Heat treatments caused significant HSP72 formation in lung,
      liver, kidney, and small intestine, but much lesser formation in heart, brain,
      and abdominal wall muscle. Additional experiments demonstrated that the
      protective effect of hyperthermic treatments against an endotoxin challenge
      occurred early, i.e., 1 and 2 h after heating, was maximal at 12 h, and had
      significantly diminished by 48 h. The formation and decay of HSP72 demonstrated a
      time course that paralleled the survival curve from endotoxin challenge, thus
      suggesting a possible role for HSP72 in the protective effect. Surprisingly, and
      in contrast to studies reported in incubated cells, endotoxin alone did not cause
      significant formation of HSP72 in vivo.

PMID- 8285290
TI  - Integrating behavior and cardiovascular responses: posture and locomotion. I.
      Static analysis.
AB  - Heart rate, arterial blood pressure, and renal and mesenteric or femoral blood
      flow were telemetered from 11 Papio hamadryas in an untethered free-ranging
      situation. The animals' behavior was recorded on videotape, and the
      cardiovascular (CV) data were recorded on the audio channels of the tape. The
      behavior was coded, and the codes were linked to the CV data via a time-code
      generator and computer control. The CV data were digitized into 1-s intervals,
      and the static relations between CV measures and the postures/locomotions (P/Ls)
      associated with the behavior were analyzed. The total frequency distributions for
      heart rate, blood pressure, and renal conductance approximated Gaussian
      distributions, whereas femoral conductance was positively skewed. The
      distribution for renal conductance suggested that during normal waking conditions
      the kidney is not maximally dilated and may increase or decrease its blood flow.
      All distributions were highly influenced by the Sit category, which occupied 80%
      of the total time. The CV measures for all P/Ls had wide ranges, and the CV
      values associated with each P/L overlapped those for the other P/Ls. The heart
      rate and renal conductance associated with the various P/Ls showed the largest
      deviations from the grand means and therefore contributed the most to the ability
      to discriminate one P/L from another. Blood pressure varied little from one P/L
      to another. The patterns of CV variables served to distinguish particular P/Ls
      very effectively. The frequency distributions were separated best when they were
      parceled on the basis of the intensity of behavior associated with a particular
      P/L. These variations in intensity were the major cause of the overlaps in the
      frequency distributions associated with P/Ls.

PMID- 8285291
TI  - Role of prostaglandins on the renal effects of angiotensin and interstitial
      pressure during volume expansion.
AB  - This study was undertaken to determine, in anesthetized dogs, the role of renal
      prostaglandins (PG) in mediating the natriuretic response to increased renal
      interstitial hydrostatic pressure (RIHP) during extracellular volume expansion
      (ECVE) with isotonic saline. It was also determined if the intrarenal angiotensin
      II (ANG II) effects during ECVE are potentiated by the inhibition of PG
      synthesis. ECVE induced similar elevations of RIHP, natriuresis, and fractional
      lithium excretion in dogs treated (n = 7) and not treated with a PG synthesis
      inhibitor (n = 5). In other experimental groups, the effects of the intrarenal
      maintenance of ANG II levels (n = 6) by infusing captopril and ANG II into the
      right renal artery were compared with those induced by the simultaneous infusion
      of captopril, ANG II, and a PG synthesis inhibitor (n = 6). In response to ECVE,
      renal blood flow and glomerular filtration rate were similar in both kidneys when
      ANG II levels were maintained constant and were significantly higher in the left
      kidney when ANG II levels were maintained constant and PG synthesis was inhibited
      in the right kidney. However, when compared with the left kidney, the ECVE
      induced increments of natriuresis and RIHP in the right kidney were reduced by
      the same magnitude when intrarenal ANG II was maintained constant with (36 and
      53%, respectively) and without (40 and 54%, respectively) the simultaneous PG
      synthesis inhibition. Our results indicate that during ECVE, renal PGs do not
      play an important role in mediating the RIHP-induced increments in natriuresis
      and decrements in proximal sodium reabsorption. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285292
TI  - Steady-state osmotic modulation of cationic conductance in neurons of rat
      supraoptic nucleus.
AB  - Whole cell patch-clamp recordings were obtained from isolated rat supraoptic
      nucleus magnocellular neurosecretory cells (MNCs). Under current clamping,
      hyperosmolality produced by the addition of 10-30 mM mannitol depolarized each of
      25 cells tested. In contrast, reducing fluid osmolality from 295 to 265
      mosmol/kgH2O had the reverse effect, hyperpolarizing 18 of 21 MNCs. Voltage-clamp
      recordings in 43 cells revealed that the effects of hypo- and hyperosmolality,
      respectively, were caused by decreases and increases in a nonselective cation
      conductance reversing near -41 mV. Current-voltage analysis in Na(+)-free
      solution revealed that the reversal potentials of currents elicited by increases
      and decreases in osmolality both shifted to a value near -90 mV, suggesting that
      a single ionic conductance is modulated by these stimuli. The relation between
      cationic conductance and osmolality was specific, sensitive (+2.14%.mosmol
      1.kgH2O-1), and well-fit by linear regression (r = 0.96; n = 22 cells) between
      275 and 325 mosmol/kgH2O. These results indicate that MNCs express a depolarizing
      current that is active under steady-state conditions and that the up- or
      downregulation of this current contributes to the excitation or inhibition of
      these cells upon acute exposure to hypo- or hyperosmolar conditions.

PMID- 8285293
TI  - Latent learning about calcium and sodium.
AB  - We used the latent-learning paradigm to examine whether replete rats can
      recognize sodium and calcium and whether they use that knowledge to guide
      consumption when subsequently mineral deprived. Rats fed a nutritionally complete
      diet received four pairs of 17-h training trials. During one trial of each pair,
      the rats drank grape- or cherry-flavored water; during the other, they drank the
      other flavor mixed with 100 mM CaCl2 (experiment 1), 750 mM NaCl (experiment 2),
      or 584 mM (20% wt/vol) sucrose (experiment 3). The rats were then fed
      nutritionally complete, calcium-deficient, or sodium-deficient diet for 3 wk and
      were given a two-bottle preference test between the two flavors. Relative to rats
      fed complete diet, calcium-deprived rats had elevated preferences for calcium-
      and sodium-paired flavors but not sucrose-paired flavors. Sodium-deprived rats
      had elevated preferences only for sodium-paired flavors. These results provide
      evidence for the existence of innate calcium and sodium appetites in calcium
      deprived rats. They indicate that these distinct appetites are centrally
      generated behaviors and are not simply due to peripheral alterations in taste
      perception.

PMID- 8285294
TI  - The art of intuition: consequence predicts conflict.

PMID- 8285295
TI  - Understanding the relationship between transference interpretation and outcome in
      the context of other variables.
AB  - Transference interpretation has traditionally been regarded as a powerful
      distinguishing feature of dynamically oriented psychotherapy. The failure of
      early studies to demonstrate its impact on outcome may, in part, have been due to
      limitations in methodology and conceptual models. A recently completed clinical
      trial of short-term individual psychotherapy has provided evidence of
      associations between two aspects of transference interpretation and outcome. The
      two aspects were concentration (frequency expressed as a proportion of
      interventions) and correspondence (congruence with a patient formulation). The
      nature of the associations varied as a function of the patient characteristic
      known as quality of object relations. Also important was the therapeutic
      alliance. When the variables were considered together in a multivariate model and
      their relationships examined by means of multiple regression, substantial amounts
      of outcome variance were accounted for. The evidence from previous and recent
      studies suggests that technique can have an important impact on outcome in short
      term individual psychotherapy. It also indicates that the impact of technique
      should be viewed in relation to patient and relationship variables.

PMID- 8285296
TI  - Transference interpretations and long-term change after dynamic psychotherapy of
      brief to moderate length.
AB  - In our study of 43 neurotic outpatients treated with brief dynamic psychotherapy,
      a significant inverse relationship was found between frequency of transference
      interpretations and long-term outcome for the subsample of 21 patients with a
      history of high quality of interpersonal relationships. At four-year follow-up,
      only one of four such patients achieved successful dynamic change when the
      interpretive focus had been on the transference relationship, whereas three of
      four patients achieved successful dynamic change when the interpretive focus had
      been on extratransference relationships. Contrary to what we expected, the
      subsample of 22 patients with a history of low quality of interpersonal
      relationships were more able to tolerate high numbers of transference
      interpretations from early on in treatment. Interpretive work on the transference
      is ancillary to work outside the transference. This, indeed, was Freud's
      theoretical position.

PMID- 8285297
TI  - The immediate impact of transference interpretation in short-term individual
      psychotherapy.
AB  - Interpretation of transference is a hallmark of psychoanalytically-oriented
      psychotherapy. Proponents of short-term individual (STI) approaches have been
      divided on the use of the technique, some stating that the time-limited format
      does not allow for exploration of transference while others advocate a more
      active and rigorous observation of transference manifestations. Recent
      theoretical formulations regarding transference, based on a cognitive-affective
      view of how individuals structure their experience, are summarized. A rationale
      for the technique of transference interpretation (TI) in the time-limited format
      is presented. A process analysis of the immediate impact of interpretation is
      described, and findings and examples of relationships involving the accuracy of
      TI are reviewed. The findings demonstrate that TIs can have a potent impact on
      the STI therapy process if employed judiciously and based on a careful
      formulation of the psychodynamics of the patient's presenting complaint.

PMID- 8285298
TI  - Clinical and research implications of patient-therapist interaction in brief
      psychotherapy.
AB  - The study of immediate in-session processes and outcomes as possible change
      events as they vary across context has become an important research focus. In
      this paper we examined transference and nontransference interpretations, as well
      as clarifications (in-session processes) followed by patient affect or defensive
      behavior (in-session outcomes). Transference interpretations followed by affect
      are associated with a positive outcome, while interpretations and clarifications
      followed by patient defensive behavior are correlated with poor outcome. On a
      clinical level these patient responses can be thought of as sub-outcome markers.
      An affective response to a transference interpretation should serve as an
      indicator to the clinician that he/she is on the right track. Conversely,
      repeated defensive behavior by the patient should alert the therapist to consider
      a change in approach. Highly defensive patients generally have a lower level of
      object relations, less psychological flexibility, and diminished access to
      feelings. Careful exploration of the multiple factors operating simultaneously
      (and which are only slowly becoming evident to us), hopefully will yield data to
      guide future clinicians when clinical intuition is not able to make fine enough
      discriminations.

PMID- 8285299
TI  - The context of transference interpretations in analytical group psychotherapy.
AB  - Transference interpretation varies with the underlying understanding of the
      concept of transference. We view the phenomena of transference in its multiple
      connections; its relationship to countertransference, its relationship to a
      particular kind of remembering that unfolds in sequence rather than in
      representation and its relationship to working through. The transference is
      expressed in the context of a "total situation" and in order to unfold, requires
      a time-space frame which variation will modify the nature of the transference
      available for interpretation. The analytical frame applied to a group situation
      creates an environment that promotes rapid and sometimes massive regression. We
      have introduced the notion of levels of transference to account for the state of
      self/object differentiation present in the group. This varies with the amount of
      regression, and depends on the severity of splitting, projection and projective
      identification. In terms of transferential objects available in the group, we
      recognize the analyst, other members and the group as a whole. The latter carries
      the more primitive transference and the underlying phantasy structure of the
      group transactions. We briefly described some possible errors in the
      interpretation of transference and their potential consequences.

PMID- 8285300
TI  - Transference interpretations: for better or worse.

PMID- 8285301
TI  - Personality disorders: model for conceptual approach and classification. Part I:
      General model.
AB  - In this article we present data suggesting that one core deficit in personality
      represents a common dimension extending across most categories of personality
      disorders (PDs), whereas clinically discrete syndromes classified as PDs in DSM
      IIIR are categorical maladaptive types related orthogonally to the common
      borderline dimension. In a sample of 121 subjects with PDs and 67 controls,
      persons with PDs and without PDs manifested similar profiles on the Millon
      Clinical Multiaxial Inventory (MCMI) scales for various behavior styles.
      Conversely, the two groups consistently differed with respect to the MCMI
      borderline scale: in contrast to non-PD persons, those with PDs were strikingly
      more borderline and typically scored above 75 points (the latter has been
      established as the cut off for the diagnosis of Borderline PD). Likewise, persons
      with PDs scored significantly higher on the Diagnostic Interview for Borderlines
      than the control group. These results suggest that: i) most symptoms usually
      considered typical of the borderline personality characterize other PDs as well;
      ii) borderline features seem to be characteristic of persons with PDs and can be
      used to distinguish PDs vs. non-PDs. Therefore, symptoms widely regarded as
      typical of the borderline personality characterize other PDs as well. This shared
      dimension may explain the overlap in categorical diagnoses of individual PDs.
      Moreover, this shared dimension may be efficiently used as the classificatory
      principle for PDs. In Part II of this article, we present a model that classifies
      deviant behaviors in a systematic way, i.e., combines three levels of functioning
      (normal, neurotic, and borderline) with a limited number of categories of (mal)
      adaptive behavior types.

PMID- 8285302
TI  - Psychotherapy during pregnancy: opportunities and challenges.
AB  - In this article, I emphasized the developmental receptivity of pregnant women to
      psychotherapeutic interventions. I selected four psychotherapy themes,
      illustrated with examples of brief, conflict-focused interventions with pregnant
      women and their families. The first theme that I discussed was conflicts over
      increased dependency needs, and I gave clinical examples of helping to express
      and to tolerate such needs. The second theme examined was narcissistic
      disturbances and pregnancy. I discussed both the impact of a burdening maternal
      ego ideal and the attempts to reestablish a narcissistic balance through
      pregnancy. In the third theme, reconciliative themes in pregnancy, I discussed
      the identificatory struggle with the mother's mother that is reactivated by
      pregnancy, both in renegotiating separation from her and in facing issues of
      rivalry. In the last theme, working through losses while giving life, I described
      a case of mourning during pregnancy. In the discussion, I examined various
      aspects of involving expectant fathers and other family members in treatment.
      Finally, I discussed various transference phenomena, including the fetus as a
      transference object, some aspects of the transference to the therapist, and the
      integration of different transference phenomena.

PMID- 8285303
TI  - The ill therapist: therapists' reactions to personal illness and its impact on
      psychotherapy.
AB  - This paper examines the potential countertransference problems therapists face
      when they become ill. Personal illness creates conscious and unconscious dilemmas
      for therapists, and the psychotherapy relationship may be strongly affected by
      the ways in which the dilemmas are managed. Psychotherapy is a relationship based
      on trust. A therapist's illness does not necessarily damage the trust that has
      been developed; however, the handling of the illness and interruption can create
      a major rupture in the relationship. Alternatively, the therapist's illness can
      create a useful opportunity for therapeutic work. Successful management of
      countertransference is a crucial ingredient for the latter outcome. Relatively
      little has been written until recently on countertransference aspects of
      therapist illness. Available literature has noted such defenses as denial,
      omnipotent fantasies, and reaction formation against dependency and weakness.
      Illness has been seen as a problem for "older" therapists, but, in fact, illness
      can occur at any age. Illness may cause a defensive withdrawal from one's
      patients and in its most serious instance lead to total empathic failure.
      Clinical concerns for the ill therapist fall into two categories: how much (if
      any) information to give patients about the illness and how to work
      therapeutically with patients' reactions. While there are no clear guidelines, we
      recommend a flexible, common sense approach with the central focus always on the
      patient's reactions to information or to changes in the therapy. The foundation
      for decisions about information and for subsequent processing of reactions must
      be the therapist's own awareness of countertransference. We recommend
      consultation with trusted colleagues or supervisors. In addition, we emphasize
      the ethical responsibility every therapist has to provide for patients in the
      event of an emergency ahead of time. Finally, we surveyed a small number of
      experienced therapists who were known to have had personal experience with
      illness. The results indicated that decisions about giving information were not
      difficult. However, the countertransference reactions of anxiety, denial,
      sadness, and avoidance (of patient anger) were often troublesome. We recommend
      that psychotherapy training include management of therapist illness. We also
      recommend that supervisors be familiar with the countertransference aspects as
      they may be called on suddenly to give consultation. Our conclusion is that
      therapist illness is as big an event for the therapist as it is for the patient,
      and we hope that a body of literature will be developed on this important topic.

PMID- 8285304
TI  - Two models of suicide treatment: evaluation and recommendations.
AB  - Treating suicidal patients is one of the most stressful aspects of
      psychotherapeutic work. This paper describes and evaluates two models of therapy
      with suicidal patients. The crisis-intervention model, which assumes suicidal
      feelings are acute and suicide is preventable; and the continuing-therapy model,
      which emphasizes chronic suicidal feelings and posits that suicide is not
      preventable. Ethical and legal issues as well as treatment strategies from each
      model are described. Both therapy models stress the importance of assessing,
      understanding, and validating the patient's feelings as well as establishing a
      good therapeutic relationship. The crisis intervention model recommends an
      active, directive intervention while the continuing therapy model emphasizes
      ongoing therapy principles. After reviewing the different models, this article
      concludes that the assumptions of the crisis-intervention model are not supported
      while those of the continuing-therapy model are. In addition, it is concluded
      that there are more therapeutic advantages to employing the continuing-therapy
      model. These include taking short-term risks to acquire long-term gain, treating
      the patient as a responsible adult and seeing the suicidal behavior in the
      context of the total personality.

PMID- 8285305
TI  - Are psychoanalytic billing practices ethical?
AB  - The changing climate of "health care reform" and increased third-party intrusion
      into psychotherapy are raising challenges over the ethics of traditional
      psychoanalytic practices such as billing for missed sessions. The practice of
      billing for missed sessions is an integral part of some analytic psychotherapies
      and forms the basis of the field of operation of many therapies. When used in
      this way, the billing practices are unique in medicine in that only these
      therapies use billing as a part of treatment. This practice is used for a variety
      of practical reasons but especially to emphasize to patients that the therapy
      occurs in their internal lives and addresses the symbols they use in organizing
      their world view. The symbolic use of a time commitment and the obligation to pay
      for that commitment are necessary so as not to present the patient with a
      contaminated field of operation. In this way the practice is similar to many
      other areas of medicine, such as surgeries that are viewed as global procedures
      whose billing allows for time that is not actually spent in contact with
      patients. This paper discusses the clinical rationale for the ability to bill for
      missed sessions and its ethics in terms of the newer language of utilization
      review. By laying down the principle of billing as a practice parameter for an
      open-ended bundled service that is billed globally the author translates the
      practice into more modern utilization-review terminology.

PMID- 8285306
TI  - Topical pharmacotherapy for allergic rhinitis: nedocromil.
AB  - Nedocromil sodium is a mast-cell stabilizer that prevents or ablates both the
      acute and late phases of the allergic response. It is an antiinflammatory agent
      that is not a steroid. It is more potent than the currently available mast-cell
      stabilizer, cromolyn, and maintenance therapy may be possible at less frequent
      intervals than the initially recommended regimen of 4 times daily. Nedocromil for
      pulmonary administration is currently available. The nasal form has undergone
      clinical trials but has not yet been released in the United States.

PMID- 8285307
TI  - The history of otolaryngology from ancient to modern times.

PMID- 8285308
TI  - Endonasal micro-endoscopic pansinusoperation in chronic sinusitis. I. Indications
      and operation technique.

PMID- 8285309
TI  - Mitochondrial ribosomal RNA gene mutation in a patient with sporadic
      aminoglycoside ototoxicity.
AB  - PURPOSE: Aminoglycoside-induced deafness has been described in a number of
      Chinese pedigrees. In nearly all of these families, affected individuals were
      related through the maternal side. Because mitochondrial DNA is transmitted
      exclusively through mothers, it had been speculated that a mutation in the
      mitochondrial DNA might predispose these maternally related family members to
      aminoglycoside ototoxicity. Recently, we analyzed three such families with
      multiple cases of ototoxic deafness and identified a pathogenic mutation in the
      mitochondrial 12S ribosomal RNA gene at nucleotide position 1555. The purpose of
      the current study is to analyze individuals with no family history of deafness,
      who had severe hearing loss after aminoglycoside exposure, for presence or
      absence of this particular mitochondrial DNA mutation. MATERIALS AND METHODS:
      Blood was obtained from 36 Chinese individuals who became deaf after
      aminoglycoside exposure and had no family history of deafness. The DNA of these
      individuals was extracted, amplified by the polymerase chain reaction, and
      analyzed for the mitochondrial ribosomal RNA gene mutation by allele-specific
      oligonucleotide hybridization and Southern blot analysis. RESULTS: In one of
      these 36 sporadic cases, we identified the nucleotide 1555 A-->G mutation in the
      mitochondrial genome. CONCLUSION: This finding implies that a small proportion of
      individuals at risk for aminoglycoside ototoxicity harbor the specific
      mitochondrial DNA mutation identified in the familial cases. In these
      individuals, a genetic susceptibility to the ototoxic effects of aminoglycosides
      can be diagnosed, and deafness can be prevented in maternal relatives by avoiding
      the use of these antibiotics.

PMID- 8285310
TI  - Sensory interaction platform posturography in patients with Meniere's syndrome.
AB  - INTRODUCTION: The influence on balance by the peripheral vestibular disturbance
      in Meniere's disease is studied. The influence of visual and proprioceptive
      support in balance is evaluated. MATERIALS AND METHODS: Patients with recurrent
      spontaneous vertigo attacks (n = 134) were studied, 90 with Meniere's disease and
      44 with recurrent vestibulopathy. A post-urographic technique was applied with
      the patient standing on a force plate in four test conditions: (1) eyes open, (2)
      eyes closed on a stable platform, and the same two conditions on a foam rubber
      platform. Postural sway was measured for each test and the normality of the
      results were evaluated by a scoring system. Sensory interaction on balance was
      assessed by comparing the values of the test results obtained with and without
      interfering influences on the vestibular-visual-proprioceptive sensory input.
      RESULTS: The results of the posturographic data were used to subdivide the
      patients into normal and abnormal groups. Comparison of the tests with and
      without visual input as well as of the tests with undisturbed and disturbed
      proprioceptive input were used to evaluate the effect of each sensory input and
      to determine which effects were dominant. In this way a "pattern" was defined.
      The interaction effect, thus defined, was most frequently positive, however, it
      could also be negative (negative patterns). Visual effects were most frequent.
      There was no significant difference for findings between patients who were
      stabilized and nonstabilized. Negative patterns suggest a complex interaction of
      the sensory inputs. CONCLUSION: In these patients with spontaneous vertigo
      attacks, sensory interaction posturography showed an influence upon balance in
      the erect position. Different patterns of sensory interaction were found. There
      was no specific pattern for this category of patients. There was no significant
      difference related to the "stabilization" of the syndrome.

PMID- 8285311
TI  - Laser shaping of composite cartilage grafts.
AB  - INTRODUCTION: The restoration of malformations of different etiology in the head
      and neck area continue to be a problem to the reconstructive surgeon. Many of
      these problems are created by the destruction of cartilage. The success of the
      reconstructive effort very often depends on the selection of a composite
      cartilage graft of proper size, shape, and thickness, which has to replace the
      missing cartilage. Despite the best of surgeon's intentions, the postoperative
      result is not always satisfactory due to the difficulty in obtaining a cartilage
      of the proper shape. Using a carbon dioxide laser, composite cartilage samples
      0.4 to 1 mm thick taken from rabbits ears were irradiated. METHODS: Rabbit ear
      cartilage with covering epithelium was used. The thickness of the composite graft
      measured 0.4 to 1 mm. Specimens were reshaped, treated with a carbon dioxide
      laser, then immersed in saline. CONCLUSION: It was observed that it was possible
      to change the shape of the cartilage, which then had the tendency to retain its
      new form for several days. Thicker composite grafts retained the new shape more
      satisfactorily. The significance of this experiment for future corrective surgery
      in various parts of the head and neck area is evident. We anticipate that this
      technique may be useful to mold grafted cartilage for use in complex
      reconstructions such as nasal, auricular, and tracheal deformities.

PMID- 8285312
TI  - Auditory brainstem latencies in type I (insulin-dependent) diabetic patients.
AB  - INTRODUCTION: This study was undertaken to compare auditory brainstem response
      latencies in insulin-dependent diabetics, and to compare these findings with
      metabolic control, microangiopathy, neuropathy, and the duration of diabetes.
      METHODS: Auditory brainstem latencies were studied in 53 type I diabetic patients
      and 42 randomly selected nondiabetic control subjects, aged between 20 and 40
      years. Three different stimulus repetition rates (10, 30, and 50 Hz) were used.
      All subjects had normal hearing ability. RESULTS: Wave V latencies were longer in
      diabetic patients when compared with those of control subjects at all repetition
      rates. At repetition rates of 10 and 50 Hz, diabetic patients had a prolonged I-V
      interwave latency, and at a repetition rate of 50 Hz, diabetics had a longer III
      V interwave latency than control subjects. These findings indicate a central
      disturbance in the auditory pathway. Microvascular complications (retinopathy,
      nephropathy) and the duration of diabetes were associated with the prolongation
      of auditory brainstem latencies. In contrast, poor metabolic control (high
      fasting blood glucose and glycated hemoglobin A1c) at the time of the present
      study was only marginally associated with prolonged auditory brainstem latencies.
      The changes in auditory brainstem latencies associated with diabetic neuropathy
      (measured with five cardiac autonomic nervous function tests) appeared
      simultaneously with microvascular complications and in patients with diabetes of
      long duration, and thus a causative role of diabetic neuropathy in the
      pathogenesis of prolonged auditory brainstem latencies remains unsolved.
      CONCLUSION: Delayed auditory brainstem latencies in type I diabetic patients are
      probably caused by the long duration of diabetes and the microvascular
      complications associated with it.

PMID- 8285313
TI  - Near total laryngectomy with epiglottic reconstruction: long-term results in 57
      patients.
AB  - INTRODUCTION: Extended partial laryngectomy procedures may offer patients the
      potential for a cure with preservation of voice. This report characterizes our
      patients managed with near laryngectomy and reconstructed with epiglottic tissue.
      MATERIALS AND METHODS: A total of 57 patients with T1 or T2 glottic carcinoma
      undergoing total laryngectomy with epiglottic reconstruction were reviewed
      retrospectively. This group included 15 patients with T1 lesions and 42 patients
      with T2 lesions. In the standard operation the specimen includes the thyroid ala,
      both vocal cords, both false vocal cords, and one arytenoid cartilage. The
      epiglottis is mobilized and delivered inferiorly for reconstruction of the
      glottic larynx. RESULT: Tumor control was obtained in 93% of T1 patients and 79%
      of T2 patients. All patients tolerated decannulation. After a mean duration of 12
      days (range 5 to 22 days), all patients were able to swallow. Voice evaluation
      revealed 5 patients had whispery voices, 25 were difficult to understand in a
      noisy environment, and 27 were easily understood. DISCUSSION: This technique is
      an effective approach to cancer therapy with cure rates comparable to total
      laryngectomy. The main limitation of this technique is that voice recovery is
      unpredictable.

PMID- 8285314
TI  - The role of radiation therapy in the treatment of head and neck cutaneous
      melanoma.
AB  - INTRODUCTION: This study was undertaken to elucidate the efficacy of external
      beam irradiation in the treatment of head and neck malignant melanoma, in
      comparison with the efficacy of surgical excision and the efficacy of surgical
      excision combined with external beam irradiation. MATERIALS AND METHODS: A
      retrospective chart review of all patients seen at the Department of Radiation
      Oncology at the University of California at Los Angeles Medical Center with the
      diagnosis of head and neck melanoma from 1973 to 1992 was conducted. Using chi 2
      analysis, survival rates were examined for patients treated with excision alone,
      irradiation alone, and both excision and irradiation. RESULTS: Patients were
      treated with primary excision (96%), salvage excision for recurrent or residual
      disease (47%), primary irradiation (9%), post-surgical-planned irradiation (22%),
      adjuvant chemotherapy (45%), and adjuvant immunotherapy (36%). The overall
      survival rate for the entire group was 29%. For patients with recurrent or
      regional disease, survival rates were 37% for those treated with excision in
      combination with irradiation, 20% for those treated with irradiation alone, and
      19% for those treated with excision. Whereas the differences among groups were
      not statistically significant, the biologic implication is that external beam
      irradiation is effective in controlling regional disease, since the tumors
      treated with irradiation alone or excision in combination with irradiation were
      larger and more aggressive than those treated with excision alone. CONCLUSION:
      External beam irradiation is of benefit in treating patients with melanoma who
      are ineligible for salvage surgery or as an adjunctive modality in situations
      where the risk of recurrence is high.

PMID- 8285315
TI  - Prosthetic voice restoration with the tracheostomal valve: a clinical experience.
AB  - INTRODUCTION: Tracheoesophageal puncture (TEP) and use of a voice prosthesis is
      not a panacea for all laryngectomies. This report presents results of
      longitudinal treatment of 24 patients with secondary TEP followed longitudinally
      for 10 years in a private practice setting. Unique to this report is a focus on
      the use of the entire voice restoration system including both the voice
      prosthesis and the automatic tracheostomal valve. METHODS: All patients referred
      for secondary TEP between 1982 and 1992 are included. Voice quality and the
      longevity of vocal restoration were ascertained. Clinical problems and their
      solutions are reported. RESULTS: Immediate vocal restitution was achieved in 19
      of 24 patients. Voicing was produced in two more patients within a few weeks.
      Four patients were not available for long-term follow-up because of death due to
      recurrent disease. Overall, 60% of patients were rated excellent and 5% rated
      fair in communication over a long-term period. Thirty-five percent were rated
      failure. DISCUSSION: TEP and the use of the voice restoration system enabled both
      hands to be free during speaking and is achieved by many laryngectomies. Patient
      evaluation, training, and follow-up with team problem-solving may increase
      success rates using this approach.

PMID- 8285316
TI  - Diagnosis and management of latex allergy in surgical patients.

PMID- 8285317
TI  - Invasive aspergillosis of the temporal bone: an unusual manifestation of acquired
      immunodeficiency syndrome.

PMID- 8285318
TI  - The etiologic role of frontal sinusitis in pediatric orbital abscesses.

PMID- 8285319
TI  - A time to die?

PMID- 8285320
TI  - Elderly patients' preferences concerning life-support treatment.
AB  - The preferences of 118 elderly patients, aged from 70 to 97 years, concerning the
      institution of artificial ventilation in the event of an overwhelming illness,
      were investigated using a questionnaire. Most patients wanted treatment if the
      outcome was likely to be good, but in approximately half, the desire for
      treatment declined as anticipated quality of life or chances of recovery fell.
      Forty percent wanted to make the decision about institution of artificial
      ventilation themselves if mentally competent and 24% wanted to use some form of
      advance directive if mentally incompetent.

PMID- 8285321
TI  - Haemodynamic responses to surgery in brain-dead organ donors.
AB  - In a prospective study we documented the haemodynamic response to surgery in 14
      brain-dead organ donors. The haemodynamic responses to the first 30 min of
      surgery were predominantly due to alterations in vascular resistance. The mean
      systemic vascular resistance increased significantly (p = < 0.01) from 936 to
      1217 dyn.s.cm-5 after 6 min, then decreased significantly (p = < 0.001) to 642
      dyn.s.cm-5 after 30 min of surgery. In two patients, the decrease in systemic
      vascular resistance was associated with haemodynamic decompensation. The left
      cardiac work index increased significantly (p = < 0.05) during surgery. We
      conclude that retrieval surgery causes significant haemodynamic effects. The
      early effects are predictable and may jeopardise organ perfusion. We advance
      arguments that organ preservation may be compromised by the use of inotropic
      agents. When practical, we suggest that a pulmonary artery catheter should be
      used during retrieval surgery in multi-organ donors to facilitate a reduction in
      the use of inotropic drugs.

PMID- 8285322
TI  - True patient-controlled sedation.
AB  - A modified patient-controlled analgesia pump provided doses of propofol 3 mg or
      midazolam 0.1 mg in 0.3 ml, over 5.4 s, with no lockout, during transvaginal
      oocyte retrieval. Alfentanil 0.2 mg was administered at three points during the
      procedure, and on request. Patients were randomly assigned to receive either
      propofol (25 patients) or midazolam (22 patients). The mean age, weight, duration
      of procedure and dose of alfentanil were similar in both groups. Onset of
      sedation with propofol or midazolam took 70.6 (SD 22.4) and 106.3 (50.7) s
      respectively. Mean doses over the first 5 min were midazolam 2.7 (1.2) mg, and
      propofol 54 (18) mg. Thereafter requirements decreased: midazolam 0.065 (0.065)
      mg.min-1, propofol 2.1 (1.3) mg.min-1. All patients successfully completed the
      procedure; none required additional sedation. P-deletion, reaction time, and
      critical flicker fusion tests revealed similar depression in both groups
      immediately postoperatively. After 30 min the p-deletion and critical flicker
      fusion scores were still impaired in the midazolam, but not in the propofol,
      group.

PMID- 8285323
TI  - An evaluation of a new self-adhesive patch preparation of amethocaine for topical
      anaesthesia prior to venous cannulation in children.
AB  - A new preparation of amethocaine in the form of a self-adhesive patch, designed
      to provide topical cutaneous anaesthesia prior to venous cannulation, was
      evaluated in an open study of 189 children. The new preparation of amethocaine
      was in place for a mean time of 48 min (SD 3.9). Eighty percent of patients had a
      satisfactory degree of analgesia for venous cannulation. Nine percent of patients
      experienced moderate pain and 11% experienced severe pain during venous
      cannulation. In 26% of patients there was slight (24%) or moderate (2%) erythema
      at the site of application, and in 5% slight oedema was noted at the site of
      application. Eight percent of patients had slight itching and 1% had moderate
      itching at the site of application. There was a clinical impression that venous
      dilatation made cannulation easier than with EMLA cream. These results suggest
      that this convenient preparation of amethocaine is highly effective at providing
      adequate topical cutaneous anaesthesia with a short onset time and a low
      incidence of minor side effects with no evidence of systemic toxicity.

PMID- 8285324
TI  - Bacterial growth in isoflurane vapour.
AB  - Pathogenic bacteria were grown on nutrient agar in a mixture of air and
      isoflurane vapour, and in air alone. The presence of isoflurane vapour in
      concentrations considerably in excess of those used either for anaesthesia or for
      sedation in intensive care had no effect either on the rate of bacterial growth
      or on the viability of colony forming units.

PMID- 8285325
TI  - Respiratory arrest following extradural sufentanil.

PMID- 8285326
TI  - Concealed Wolff-Parkinson-White syndrome detected during spinal anaesthesia.
AB  - We report a case of concealed Wolff-Parkinson-White syndrome detected for the
      first time during spinal anaesthesia in an adult male. Episodes of
      tachyarrhythmia with a heart rate of approximately 115 beat.min-1, wide QRS
      complexes and negative T waves which lasted 30-60 s, but were unassociated with
      hypotension, occurred three times after spinal anaesthesia. Postoperative Holter
      ECG monitoring showed the frequent occurrence of supraventricular premature
      contractions and paroxysmal supraventricular tachycardias with the same
      electrophysiological characteristics as those noted during spinal anaesthesia.
      The patient was diagnosed as having concealed Wolff-Parkinson-White syndrome.
      Since this condition is asymptomatic and undetectable by routine pre-operative
      screening it is likely that other unsuspected cases will arise. When episodes of
      tachyarrhythmia occur unexpectedly during anaesthesia, as was the case in this
      patient, postoperative examination including Holter ECG monitoring will be
      necessary to determine the nature and severity of the tachyarrhythmia.

PMID- 8285327
TI  - Successful use of continuous veno-venous haemofiltration to treat profound fluid
      retention in severe peripartum cardiomyopathy.
AB  - The use of continuous veno-venous haemofiltration after failure of conventional
      treatment in a patient with severe peripartum cardiomyopathy is described.
      Treatment with inotropes and diuretics failed to produce a diuresis despite the
      presence of severe fluid overload. Haemofiltration over a 9-day period allowed
      removal of 171 of fluid with a concomitant improvement in haemodynamic function
      and a spontaneous diuresis.

PMID- 8285328
TI  - Intercostal neuralgia associated with internal mammary artery grafting.
AB  - Two patients who underwent coronary artery bypass grafting in which the internal
      mammary arteries were used, developed chronic, atypical chest pain. After further
      investigation a diagnosis of intercostal neuralgia was made. It is thought that
      this condition is due to damage to the intercostal nerves when the internal
      mammary arteries are dissected. Intercostal neuralgia should be included in the
      differential diagnosis of chest pain after coronary artery surgery, as its
      recognition may save the patient unnecessary investigation and suffering.

PMID- 8285329
TI  - Controlled ventilation with the Bain co-axial system. A rationalisation of gender
      related minute volume requirements and carbon dioxide replacement therapy.
AB  - The minute ventilation required to maintain either hypocapnia (FE'CO2 = 4.0 kPa,
      group A, n = 36) or normocapnia (FE'CO2 = 5.0 kPa, group B, n = 38) in 74 adult
      patients was determined for the Bain system with controlled ventilation at 10
      breath.min-1 and fresh gas flow equal to minute ventilation. Males required a
      greater minute ventilation and fresh gas flow than females (p < 0.01) in each
      group (group A, males approximately 90 ml.min-1.kg-1, females approximately 80
      ml.min-1.kg-1; group B, males approximately 75 ml.min-1.kg-1; females
      approximately 65 ml.min-1.kg-1). Where capnography is not available, it may be
      safer to ventilate patients' lungs using the minute volume and fresh gas flow
      requirements established in group A patients. The administration of 5% carbon
      dioxide in oxygen for 2 min safely re-established normocapnia and spontaneous
      respiration in hypocapnic patients when ventilated with the same minute volume,
      fresh gas flow and respiratory rate required during surgery. Only one patient
      required greater than 400 ml.min-1 of carbon dioxide to produce a 5%
      concentration. Maximum flow from the carbon dioxide flowmeter may be restricted
      to 400 ml.min-1 rather than the 500 ml.min-1 currently recommended.

PMID- 8285330
TI  - A study of laryngeal mask inflation. Pressures exerted on the pharynx.
AB  - Laryngeal mask airway cuff inflation pressures were measured when inflated with
      the same volume of gas firstly in free space and then in position in the pharynx.
      A large difference in these pressures was observed and this was related to
      pharyngeal mucosal perfusion pressure. This study shows that it may be easy to
      produce pressures on the pharyngeal mucosa in excess of the critical perfusion
      pressure and thus potentiate mucosal trauma. Furthermore, laryngeal mask cuff
      pressures were measured at intervals during anaesthesia and were found to rise by
      a significant amount if room air was used as the cuff inflating gas. This effect
      could, however, be reversed if inspired gas was used to inflate the mask cuff. We
      conclude that care must be taken when inflating the laryngeal mask cuff if
      postoperative morbidity is to be avoided and also that it may not be necessary to
      use as high a volume of inflating gas as has been recommended during spontaneous
      respiration.

PMID- 8285331
TI  - A split laryngeal mask as an aid to training in fibreoptic tracheal intubation. A
      comparison with the Berman II intubating airway.
AB  - Thirty patients were randomly allocated to one of two groups in order to compare
      the use of a split laryngeal mask airway with the Berman II airway as aids to
      training in fibreoptic laryngoscopy. In both groups anaesthesia was induced with
      propofol and maintained with isoflurane in N2O/O2 (FIO2 = 0.5). The fibreoptic
      laryngoscope was guided towards the larynx using the split laryngeal mask airway
      in group 1 and the Berman airway in group 2. The tracheas of all patients were
      successfully intubated at the first attempt and no patient's peripheral oxygen
      saturation decreased below 92%. Two min after intubation mean heart rate was
      significantly greater in group 1 (101 beat.min-1) than in group 2 (84 beat.min-1)
      (P < 0.05). The split laryngeal mask is a useful aid to training in fibreoptic
      intubation and may allow better airway control than the Berman II intubating
      airway.

PMID- 8285332
TI  - A modified sensor for pulse oximetry in children.
AB  - Pulse oximetry is a powerful tool for patient monitoring but there are practical
      problems with its application in small children. Standard probes may be too large
      to be used easily and dedicated paediatric probes may be awkward to apply. The
      authors describe a modification of the Nellcor 'Oxiband' probe which simplifies
      its use in children. The modified probe was compared in 27 children with the
      conventional 'clothes-peg' type of device and found to under-read by 1.5% with
      95% confidence intervals of +/- 3.1%. This is comparable to the error of the
      'Oxiband' probe in normal use of +/- 3% over the range of saturations 70-95%. It
      is concluded that the modified probe may safely be used in clinical practice.

PMID- 8285333
TI  - A comparison of epidural diamorphine with intravenous patient-controlled
      analgesia using the Baxter infusor following caesarean section.
AB  - In a randomised study of analgesia following Caesarean section, we compared the
      efficacy and side effects of on-demand epidural diamorphine 2.5 mg with
      intravenous patient-controlled analgesia using diamorphine from the Baxter
      infusor system. Pain scores fell more rapidly in the epidural group, but by the
      fourth hour, and thereafter, both techniques had a similar analgesic effect. The
      patient-controlled analgesia group used significantly more diamorphine (p <
      0.001), median 62 mg (range 18-120 mg) compared to the epidural group, median 10
      mg (range 2.5-20 mg), over a significantly longer time period (p < 0.001), median
      54.25 h (range 38-68 h) compared to the epidural group, median 40.75 h (range 6
      70 h). The frequency and severity of nausea, vomiting and pruritus were similar
      in the two groups, however, the patient-controlled analgesia group were more
      sedated during the first postoperative day. This reached statistical significance
      (p < 0.05) between 9-24 h. Overall satisfaction scores (0-100) were high, but the
      patient-controlled analgesia group scored significantly higher: mean 85.5 (SD
      12.2) compared to mean 77.0 (SD 11.7) in the epidural group.

PMID- 8285334
TI  - Comparison of 2-chloroprocaine and prilocaine for intravenous regional
      anaesthesia of the arm: a clinical study.
AB  - In a double-blind, randomised study of patients scheduled for minor hand surgery
      0.5% 2-chloroprocaine (n = 30) and 0.5% prilocaine (n = 30) in a volume of 40 ml
      were compared for intravenous regional anaesthesia. The onset of sensory and
      motor block and recovery of sensory block were determined, and the occurrence of
      side-effects was noted. Twenty-four patients in the 2-chloroprocaine group and 17
      in the prilocaine group developed complete sensory block by 15 min after
      injection (p < 0.05). Complete recovery of sensation was faster after prilocaine
      (7.1 min) than 2-chloroprocaine (9.8 min) (p < 0.01). Venous irritation and/or
      urticaria after tourniquet release was observed on 10 occasions in those
      receiving 2-chloroprocaine and twice in those receiving prilocaine. An increase
      in heart rate of > 20% above control values occurred in three patients, all of
      whom had been given 2-chloroprocaine. Clinically, local anaesthetic properties of
      0.5% 2-chloroprocaine and prilocaine were similar, but there were more side
      effects with the former drug.

PMID- 8285335
TI  - Atelectasis and oxygenation in major surgery with either propofol with or without
      nitrous oxide or isoflurane anaesthesia.
AB  - Forty-two patients undergoing major colonic surgery were assigned at random to
      receive isoflurane-fentanyl anaesthesia with nitrous oxide in oxygen, propofol
      fentanyl anaesthesia with air in oxygen or propofol-fentanyl anaesthesia with
      nitrous oxide in oxygen. The groups were comparable in demographic data.
      Atelectases were identified, and the area measured by computerised tomography of
      the chest 203 +/- 69 min after extubation, and oxygenation was determined by
      arterial blood gas samples taken during operation at 30, 60, 90 and 120 min after
      extubation and on postoperative days 1, 2 and 3. Atelectases were seen in all
      three groups with no differences in the mean area between groups. After
      operation, the effect of 4 l.min-1 of oxygen by nasal catheter on PaO2 was
      similar in all groups. A significant decrease in PaO2 was found during the first
      3 days after surgery, and was also the same in all groups. There was no
      correlation between area of atelectasis and postoperative PaO2. We conclude there
      is no difference in the incidence of postoperative atelectasis or oxygenation
      when using propofol, with or without nitrous oxide or isoflurane.

PMID- 8285337
TI  - Where now? The anaesthetists development in management.

PMID- 8285336
TI  - Suxamethonium-induced muscle pains are not related to cholinesterase activity.
AB  - We have investigated the possibility of using the pre-operative measurement of
      cholinesterase activity to predict the postoperative development of myalgia
      following the administration of suxamethonium. Seventy-seven patients presenting
      for elective extraction of wisdom teeth were entered in the study. All patients
      received a standard anaesthetic regimen, including suxamethonium to facilitate
      tracheal intubation, and standardised postoperative analgesia. Myalgia was
      assessed postoperatively and no correlation between muscle pains and
      cholinesterase activity was found.

PMID- 8285338
TI  - Muscle rigidity in meningococcal meningitis.

PMID- 8285339
TI  - Laryngeal mask placement in the prone position.

PMID- 8285340
TI  - The reinforced laryngeal mask airway for laser pharyngoplasty.

PMID- 8285341
TI  - Cardiac output measurement and continuous venovenous haemofiltration.

PMID- 8285342
TI  - Use of the Servo 900C ventilator for nasal positive pressure ventilation.

PMID- 8285343
TI  - Extradural air as a cause of paraplegia.

PMID- 8285344
TI  - Extradural air as a cause of paraplegia.

PMID- 8285345
TI  - Extradural anaesthesia and air.

PMID- 8285346
TI  - Acute porphyria and propofol.

PMID- 8285347
TI  - Right sided aortic arch--diagnosis by pulse oximetry.

PMID- 8285348
TI  - Peribulbar anaesthesia and aspirin.

PMID- 8285349
TI  - Deflated tracheal tube cuff with inflated pilot balloon.

PMID- 8285350
TI  - Awaiting the levering laryngoscope.

PMID- 8285351
TI  - Does a bloody tap prevent postdural puncture headache?

PMID- 8285352
TI  - Cricoid pressure and potential spine injuries.

PMID- 8285353
TI  - Broken O-ring causing hypoventilation.

PMID- 8285354
TI  - Oxygen flush buttons: more critical incidents.

PMID- 8285355
TI  - Mivacurium in electroconvulsive therapy.

PMID- 8285356
TI  - Anaesthesia and undiagnosed Jervell and Lange-Nielsen syndrome.

PMID- 8285357
TI  - Mechanism of antiemetic effect of ginger.

PMID- 8285358
TI  - Training in pain management.

PMID- 8285359
TI  - A knotty problem.

PMID- 8285360
TI  - 'Just a scratch': harmless, but not necessarily trivial.

PMID- 8285361
TI  - [Arterial steal via an arteriovenous fistula for hemodialysis. A clinical case
      and review of the literature].
AB  - We related a case of arterial atrappment in the left upper limb by an
      arteriovenous humerus-cephalic hyperfunctioning fistula. Surgical procedure
      consisted on the insertion of a PTFE's banding around the arterialized vein
      obtaining satisfactory clinic and functional results. We review in the
      literature, the frequency the pathogeny and the therapeutics possibilities.

PMID- 8285362
TI  - [An inflammatory aortic aneurysm ruptured into the retroperitoneum and an
      extensive communication of the aneurysm with the vena cava inferior].
AB  - Aortocaval fistula is a rare complication of abdominal aortic aneurysms that
      occurs with a frequency of 1% of operative cases or less. In this report we
      present a case of aortocaval fistula associated with ruptured and inflammatory
      aortic aneurysm that became apparent after evacuation of the thrombus. The
      inferior cava was ligated. We discuss the clinical syndrome and the management of
      patients with aortocaval fistula secondary to an abdominal aortic aneurysm and
      the results of surgical repair.

PMID- 8285363
TI  - [Major vascular complications following surgery for a herniated lumbar disk].
AB  - Two cases of arterial injury of the iliac arteries during surgery of the lumbar
      disc are presented. Both patients were successfully operated, in the first case a
      primary repair was accomplished, the second patient was treated by means of an
      ileo-femoral bypass graft. A comment of the pathophysiology, diagnostic and
      surgical management of this unusual complication is presented.

PMID- 8285364
TI  - [Prosthesis interposition in the case of subclavian artery transposition].
AB  - When we can't realize the reimplantation because of technical difficulties,
      special cases are presented during transposition from the subclavian artery to
      the primitive carotid artery. In these cases, between primitive carotid artery
      and the subclavian artery and also the vertebral artery, Gore-tex's tubes were
      implanted with favourable results.

PMID- 8285365
TI  - [Arteriosclerosis obliterans and ozone therapy. Its administration by different
      routes].
AB  - We report 72 non-diabetic patients with obliterant atherosclerosis, stadium II,
      (intermittent claudication). The medium age of these patients was 62 +/- 4.5
      years old. They were randomly included into four groups. Three were treated with
      Ozone: one of them by endovenous way, other intramuscular way, and the last one
      by rectal way; meanwhile, in the fourth group the patients were submitted to
      conventional medical treatment (control group). In the three ozone-groups there
      weren't differences when they were compared between then. But there was a
      significant improvement in comparison with the control group. The claudication
      distance in the treadmill increased to the 2.5 km/hour. Ankle/arm pressure rates
      hadn't significant differences, this corroborates the ozone action on the
      microcirculation. The least uncomfortable, the more harmless and the more
      economic way was the rectal way.

PMID- 8285366
TI  - [Blood groups as a risk factor in venous thrombosis].
AB  - We report 173 patients with venous thrombosis (or post-thrombotic syndrome)
      demonstrated by phlebography. We show up the importance of blood groups as risk
      factor, being very significant the A group. Female sex is associated with a high
      incidence of this pathology. A frequent location is the left lower limb.

PMID- 8285367
TI  - [The clinical indications for and risks of fresh frozen plasma. A consensus
      conference. The Ministry of Health and Consumer Affairs].

PMID- 8285368
TI  - Total occlusion of left main coronary artery in Orientals: profile of 4 cases.
AB  - The authors report 4 Oriental cases of total occlusion of the left main coronary
      artery (LMCA) with differing presentations. The first patient had a twelve-year
      history of stable angina pectoris. The second patient had angina for a year,
      which became unstable two months prior to diagnosis. The third patient had
      myocardial infarction seven years ago and presented with a one-month history of
      rest angina. The fourth patient had stable effort angina for six years but
      presented with accelerated angina three months prior to diagnosis. The incidence
      of total occlusion of the LMCA is rare and survival depends on the existence of
      collateral circulation. In LMCA disease, there is usually disease in other parts
      of the coronary arterial tree, and hence, the need for urgent coronary bypass
      surgery.

PMID- 8285369
TI  - Coronary angioplasty in the elderly: immediate and long-term results.
AB  - Coronary angioplasty was performed in 37 elderly patients (> sixty-eight years)
      with unstable or stable angina, refractory to medical treatment. History of
      myocardial infarction was present in 38% and of previous bypass surgery in 5% of
      patients. Coronary angiography revealed single-vessel disease in 22 (59%) and
      multivessel disease in 15 (41%) of patients. The mean left ventricular ejection
      fraction was 53 +/- 17%. Percutaneous transluminal coronary angioplasty (PTCA)
      was successful in 92% of patients; there were two angioplasty failures and 1
      acute occlusion leading to Q wave myocardial infarction. In patients with
      multivessel disease complete revascularization was achieved in 33%. Follow-up
      data (21.29 +/- 9.23 months) are available in all patients with primary
      angiographic success. There was 1 death. Seventy-nine percent of patients had an
      improved anginal status, and repeat PTCA was performed in 2 patients because of
      clinical recurrence. Thus, coronary angioplasty is a safe and efficacious method
      of revascularization in symptomatic patients over the age of sixty-eight years.

PMID- 8285370
TI  - Coronary flow reserve measurements with a new Judkins-style Doppler angiographic
      catheter.
AB  - The authors assessed whether measurements obtained by Judkins-style Doppler
      catheters are comparable to those achieved with the intracoronary Doppler
      technique in 42 patients with normal coronary arteries on angiography (19
      syndrome X and 23 heart transplant patients). Resting coronary flow velocity and
      response to a hyperemic intracoronary dose of papaverine was measured with a
      Judkins-style, 8F Doppler-tipped catheter positioned in the left coronary ostium
      and a 3.6F intracoronary Doppler catheter positioned in the proximal left
      anterior descending artery. Mean coronary flow velocity at rest was significantly
      higher with the Judkins Doppler (10.1 +/- 4.6 vs 6.3 +/- 4.5 cm/sec, p < 0.01).
      The mean coronary flow velocity at peak hyperemia was also significantly higher
      with the Judkins Doppler (33.7 +/- 14.1 vs 19.7 +/- 11.5 cm/sec, p < 0.01).
      Coronary flow reserve was 3.57 +/- 1.3 with the Judkins Doppler and 3.47 +/- 1.2
      with the intracoronary Doppler (r = 0.85). A second study was performed in 14
      heart transplant patients with the intracoronary Doppler positioned in the left
      main coronary artery. The resting and hyperemic flow velocities were again higher
      with the Judkins Doppler but the differences were not statistically significant.
      There was again a strong correlation between the Doppler catheters for coronary
      flow reserve measurements. The Judkins-style Doppler technique appears to be a
      quick, safe, and accurate alternative to the intracoronary Doppler technique.

PMID- 8285371
TI  - Precise assessment of myocardial damage associated with secondary
      cardiomyopathies by use of Gd-DTPA-enhanced magnetic resonance imaging.
AB  - To evaluate the myocardial damage in patients with secondary cardiomyopathies,
      the authors examined gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)
      enhanced magnetic resonance imaging (MRI) in 5 patients (2 with cardiac
      amyloidosis, 2 with acute myocarditis, 1 with cardiac thyrotoxicosis). MR images
      were performed at 1.5-T by using a spin echo pulse sequence before and after
      intravenous administration of Gd-DTPA (0.2 mmol/kg). All patients revealed
      distinct high-intensity areas on postcontrast images. Moreover, MRI with Gd-DTPA
      could determine the severity and precise regions of myocardial damage associated
      with secondary cardiomyopathies. It is suggested that gated cardiac MRI with Gd
      DTPA enhancement is useful for detecting the myocardial damage in secondary
      cardiomyopathies.

PMID- 8285372
TI  - Effects of glyceryl trinitrate on blood pressure and arterial compliance.
AB  - Glyceryl trinitrate (GTN) mainly reduces systolic blood pressure (SBP) rather
      than diastolic blood pressure (DBP) in acute conditions. To examine the efficacy
      of GTN as an antihypertensive agent in patients with isolated systolic
      hypertension (ISH), the authors examined the effects of GTN on BP and arterial
      compliance (AC) in patients who underwent cardiac catheterization. Seventy
      patients (with old myocardial infarction, 36; angina pectoris, 25; chest pain
      syndrome, 9) who underwent cardiac catheterization because of chest pain were
      included in this study. They were aged between thirty-seven and seventy-four
      (mean sixty-one) years. According to the levels of BP at cardiac catheterization,
      the authors selected two subgroups: the normotensive group (NT group, n = 18) and
      the isolated systolic hypertensive group (ISH group, n = 20) from all subjects.
      The authors measured BP before and after (three minutes) sublingual
      administration of GTN (0.3 mg) at the cardiac catheterization. AC was assessed by
      means of diastolic pressure decay. The change of BP was estimated by the
      differences between values before and at three minutes after GTN. After
      administration of GTN, SBP was decreased significantly from 157 +/- 25 to 142 +/-
      23 mmHg (P < 0.01), while DBP did not change (83 +/- 13 vs 84 +/- 15 mmHg). The
      change in SBP was positively correlated with the pretreatment SBP and negatively
      correlated with AC (r = 0.51, P < 0.001; r = 0.39, P < 0.001, respectively). AC
      was significantly lower in the ISH group than in the NT group (P <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285373
TI  - The left ventricular end-systolic pressure and pressure-volume index. Comparison
      between invasive and auscultatory arm pressure measurements.
AB  - The slope of the left ventricular (LV) end-systolic pressure-volume relation
      (ESPVR) has been established as a valuable clinical method to assess LV
      contractile function independent of LV loading factors. The purpose of the
      present study was to evaluate whether the ESPVR could be reliably determined from
      auscultatory blood pressure (BP) measurements and from LV volume measurement by
      contrast ventriculography (CVG). Twenty-four patients with suspected or known
      ischemic heart disease were studied by cardiac catheterization with simultaneous,
      blinded, intravascular and auscultatory pressure measurements. LV volume was
      determined by CVG. The auscultatory mean arterial blood pressure (MAP) derived
      from: [formula: see text] was found to be a useful measure of the LV end-systolic
      pressure in this connection. The correlation between invasively measured LV end
      systolic pressure (ESP) and MAP was highly significant (r = 0.82; SEE = 6.9 mmHg;
      p = 0.001). The correlation between invasively and semi-invasively measured ESPVR
      fell close to the line of identity (r = 0.99; SEE = 0.23 mmHg.mL-1; p < 0.001).
      The replacement of ESP by MAP induced only a minimal error in the assessment of
      the ESPVR. A complete noninvasive determination of the ESPVR and LV contractility
      therefore seems possible by using the MAP and by measuring the end-systolic
      volume by radionuclide ventriculography or by echocardiography.

PMID- 8285374
TI  - Hormonal and hemodynamic changes following single-dose felodipine treatment
      during mental stress.
AB  - Mental stress induces changes in hemodynamic variables and in the plasma level of
      many hormones and plasma peptides. These changes can be modulated by various
      drugs, eg, beta-blockers. In a double-blind, placebo-controlled crossover study,
      the authors evaluated the hormonal and hemodynamic changes during psychological
      stress and the effect of felodipine 10 mg (plain tablet). Eight male volunteers
      participated. Heart rate, blood pressures, and stroke volume were measured by
      ECG, mercury sphygmomanometer, and impedance cardiography. Catecholamines and
      atrial natriuretic factor in plasma were measured by electrochemical and
      radioimmunoassay techniques. A single dose of felodipine, 10 mg, exaggerates the
      heart rate decreases the left ventricular ejection time and augments the plasma
      level increment of noradrenaline. The stress-induced changes in other variables
      were not influenced by felodipine treatment. In conclusion, acute felodipine
      treatment influences the reflex activation of the sympathetic nervous system
      during psychological stress. In the treatment of patients, especially patients
      with heart disease, these findings could be important but further investigations
      in patients need to be done.

PMID- 8285375
TI  - 99Tcm-sestamibi uptake in the leg muscles and in the myocardium in patients with
      intermittent claudication.
AB  - 99Tcm-Sestamibi has now replaced 201Tl as a cardiac imaging agent. In addition to
      the myocardial uptake there is also a considerable uptake in the striated muscle,
      which may be used for analyzing the muscular perfusion. Sixteen patients with
      intermittent claudication were investigated with 99Tcm-Sestamibi-SPECT (single
      photon emission computerized tomography) in order to visualize coronary ischemic
      disease. After the registration of the myocardial perfusion they were also
      studied regarding their leg muscle perfusion. This was done at rest and during
      standardized stress test using a bicycle ergometer. In 10 of the patients there
      was an increase in the isotope uptake in the myocardium from work to rest > 10%
      reflecting pronounced myocardial ischemia, which, however, was symptomatic in
      only 4 of the patients. The muscular uptake in the myocardium of 99Tcm-Sestamibi
      in the thigh increased significantly from rest to exercise (P < 0.01), while it
      remained unchanged in the calf muscle. There were no significant correlations at
      rest between the ratio of the right and left systolic blood pressure in the
      ankles and the ratio between the right and left isotope uptake in the calves, but
      the increase in the isotope uptake from rest to work correlated with the blood
      pressure ratio at r = 0.79, P < 0.01 (anterior projection) and r = 0.71, P < 0.01
      (posterior projection).

PMID- 8285376
TI  - Left and right coronary artery to left ventricular fistula: demonstration of
      myocardial ischemia by treadmill test and Holter monitoring--a case report.
AB  - Fistulous communication from the coronary artery to the left ventricle is
      extremely rare. The authors report such a case in a sixty-year-old woman with
      chest pain. They demonstrated myocardial ischemia on treadmill test and Holter
      monitoring in this patient.

PMID- 8285377
TI  - Transluminal angioplasty of a single coronary artery anomaly during acute
      myocardial infarction--a case report.

PMID- 8285378
TI  - Clonidine for painful diabetic-uremic leg cramps and pruritus--a case report.

PMID- 8285379
TI  - Colorflow duplex ultrasonography determines the presence and nature of
      vasculogenic headaches.
AB  - Eighteen consecutive patients with severe headache syndromes underwent
      noninvasive interrogation to explore the intracranial vascular involvement in
      their headaches. The authors used a colorflow duplex scanner with a 2.25 MHz,
      tightly curved, phased-array transducer to insonate and visualize the terminal
      segments of the vertebral arteries; the anterior, middle, and posterior cerebral
      circulations; and the basilar artery. Blood flow velocities and vessel caliber
      were obtained during a headache-free period and during a grade 8-10 headache in
      all patients. Comparisons of these data indicated that 14 of the 18 patients had
      demonstrable arterial changes associated with their headaches. Of these 14, 4
      patients were found to have marked vasospasm of at least two of the arteries in
      the Circle of Willis and/or the vertebrobasilar system. The remaining 10 patients
      had headaches associated with intracerebral vasodilation. The authors conclude
      that color flow duplex ultrasonography of the intracerebral arteries is capable
      of determining the presence and mode of vascular headache development.

PMID- 8285380
TI  - Doxazosin withdrawal and ambulatory blood pressure monitoring in normotensive
      subjects.
AB  - The effect of doxazosin withdrawal on normotensive subjects was examined by
      ambulatory blood pressure monitoring (ABPM) during twenty-four hours. Eight
      normotensive volunteers were treated with doxazosin for four weeks. ABPM was done
      the day before withdrawal and on the second and seventh days after withdrawal.
      The average systolic and diastolic BP were not altered by doxazosin withdrawal
      either on day 2 or day 7, but pulse rate (PR) decreased on day 2 and day 7.
      Daytime PR decreased on day 2, but both daytime and nighttime PR decreased on day
      7. On withdrawal of doxazosin, the plasma norepinephrine concentration decreased
      and the plasma renin activity tended to decrease. Neither overshooting
      hypertension nor cardiovascular event was related to doxazosin withdrawal was
      observed. It is concluded that, in normotensive subjects, discontinuation of
      doxazosin may result in bradycardia without hypotension or signs of withdrawal
      syndrome.

PMID- 8285381
TI  - Platelet-activating-factor-induced changes in cardiovascular function and
      oxyradical status of myocardium in presence of the PAF antagonist CV-6209.
AB  - The effects of platelet-activating factor (PAF) on cardiac function and
      contractility and its mechanism of action are not fully understood. The authors
      investigated the effects of PAF in the absence or presence of a potent PAF
      antagonist CV-6209 on the cardiac function and contractility; lipid peroxidation
      product malondialdehyde (MDA), an indirect measure of oxygen free radicals; serum
      creatine kinase (CK); blood lactate; and pH in anesthetized dogs. CV-6209 (1
      mg/kg, IV) did not produce significant changes in the various parameters studied.
      PAF (1 microgram/kg, IV) produced decreases in the cardiac function (cardiac
      index, left ventricular work index) and indices of cardiac contractility [(+) and
      (-) dp/dt, dp/dt at CPIP, (dp/dt)/IP, dp/dt at CPIP/IP, Vmax] and increases in
      the systemic and pulmonary vascular resistance. It also produced increases in
      cardiac MDA, serum CK, blood lactate, and H+ and decreases in blood pH and HCO3-.
      CV-6209 completely prevented the PAF-induced changes in the hemodynamic and
      biochemical parameters. These results suggest that PAF-induced cardiac depression
      may be due to PAF-induced release of oxyradicals from neutrophils and that PAF
      antagonist may be useful in counteracting the deleterious effects of PAF on the
      cardiovascular system.

PMID- 8285382
TI  - Nailfold capillaroscopy in the screening and diagnosis of Raynaud's phenomenon.
AB  - Raynaud's phenomenon is in most cases idiopathic, but it may appear as secondary
      to other diseases. Since clinical evaluation is often inadequate to distinguish
      between these two forms, simple noninvasive methods are needed for an early
      diagnosis of the secondary form. The authors used nailfold capillaroscopy to
      study 58 patients with Raynaud's phenomenon--44 apparently idiopathic and 14
      secondary to connective tissue diseases. In all patients affected by secondary
      Raynaud's phenomenon nailfold capillaroscopy confirmed the presence of an
      abnormal pattern with typical systemic sclerosis alterations in 5 cases. Twenty
      one (48%) of the other 44 patients presented a normal capillaroscopic pattern, 15
      (34%) had alterations compatible with long-term idiopathic Raynaud's phenomenon,
      and 8 (18%) showed abnormal capillaroscopic patterns, 2 of which were identified
      as the sclerodermic pattern. Nailfold capillaroscopy distinguishes between
      primary and secondary Raynaud's phenomenon and may be used to identify patients
      presenting no evidence of underlying disease who could be at risk of developing
      connective tissue disease.

PMID- 8285384
TI  - Prevalence, clinical features, and acute course of atypical myocardial
      infarction.
AB  - Ninety-four consecutive patients (60 men and 34 women; mean age 68.5 +/- 11.5
      years) with acute myocardial infarction (MI) were investigated retrospectively,
      in order to evaluate the prevalence, clinical features, and short-term course of
      the atypical forms (symptoms other than chest pain). An atypical MI was found in
      30 patients, with a prevalence of 32% (95% confidence limits 27-36%). It was most
      prevalent in women above sixty-five years old (P < 0.05). Abdominal pain,
      paroxysmal dyspnea, and pulmonary edema were the most frequent symptoms (33%,
      17%, 13%, respectively). No differences were observed between typical and
      atypical MI in regard to risk factors (hypercholesterolemia, arterial
      hypertension, diabetes mellitus, cigarette smoking) and history of MI,
      cerebrovascular disease, peripheral vascular disease, or chronic lung disease.
      Significantly fewer patients with atypical MI had a history of angina pectoris (P
      < 0.05). No differences were observed in regard to previous medication, except
      for antiarrhythmic drugs, more often used by atypical patients (P < 0.05).
      Location and severity of MI (as judged by ECG and peak levels of creatine kinase
      in the serum) were similar in both subgroups, as were the complications (34%
      typical and 50% atypical) and death rate (12.5% and 16.7%, respectively). In
      conclusion, atypical MI is not less severe than typical. This emphasizes the need
      for a high suspicion index in many different clinical settings, but particularly
      (although not exclusively) in elderly females, in the presence of abdominal pain
      or otherwise unexplained paroxysmal dyspnea.

PMID- 8285383
TI  - Clinical and hemodynamic effects of stepwise lowering of hemoglobin concentration
      in patients with intermittent claudication.
AB  - This study evaluates the effect of stepwise lowering of the hemoglobin (Hb)
      concentration on maximal walking distance (MWD) and hemodynamics in patients with
      intermittent claudication. The results in a study group (n = 6) were compared
      with those of a control group (n = 6) whose members were not subjected to
      venesections. An average decrease of Hb concentration from 151 +/- 4 to 121 +/- 3
      g/L did not significantly influence MWD, the result being 282 +/- 62 meters
      before venesections and 255 +/- 54 meters after three to five (mean four)
      repeated venesections. Transcutaneous oxygen pressure was measured at the dorsum
      of the foot before and after exercise and did not change with a gradual decrease
      of the Hb concentration. Maximal heart rate, painfree walking distance, ankle
      pressure, and blood lactate concentration were also unchanged. An average
      venesection volume of about 1.4 liters whole blood within fourteen days, without
      isovolemic replacement, did not change the blood volume, which was 5.1 +/- 0.4
      liters before and 5.0 +/- 0.5 liters after venesections. In conclusion,
      hemodilution accomplished by venesections did not have a clinically or
      physiologically beneficial effect in patients with severe intermittent
      claudication. However, hemodynamics and clinical symptoms were not affected by a
      considerable decrease in the arterial oxygen content within the normal Hb
      concentration range.

PMID- 8285385
TI  - Anomalous left coronary artery originating in the right aortic sinus with
      retroaortic course: a postmortem study.
AB  - Post-mortem study of a heart specimen from a forty-two-year-old man showed an
      anomalous origin of the left main coronary artery from the right aortic sinus and
      its course posterior to the aorta. In this case the branches of the left main
      artery were smaller than usual, being partly supplied by the right coronary
      artery, which originated in a common point with a right preventricular artery. In
      the case reported myocardial ischemic signs were not noted.

PMID- 8285386
TI  - Hyperhidrosis--a case history.
AB  - The authors present a case report on hyperhidrosis. The social and occupational
      consequences of this disease entity are discussed as well as the genetic
      implications of this disorder. The medical and surgical treatments of
      hyperhidrosis are evaluated. The use of infrared imaging techniques as a cost
      effective, rapid, noninvasive procedure to diagnose this disorder is described.

PMID- 8285387
TI  - Pain relief and clinical improvement temporally related to the use of
      pentoxifylline in a patient with documented cholesterol emboli--a case report.
AB  - A sixty-six-year-old man with known severe atherosclerosis was admitted with
      painful feet and nonblanching purpuric lesions of his toes. He had undergone
      cardiac catheterization and coronary artery bypass five and three months,
      respectively, prior to admission. Initial treatment included: stopping the
      patient's lisinopril, increasing his nifedipine dose, and adding pentoxifylline
      400 mg po tid. Within twenty-four hours pain was markedly decreased. Skin biopsy
      confirmed a diagnosis of cholesterol embolism. Pentoxifylline was stopped and
      intravenous heparin therapy was initiated. Within twenty-four hours, pain
      returned. Nitrol paste applied to the top of each foot had no effect. After forty
      eight hours, pentoxifylline was restarted. Once again, pain relief was noted
      within twenty-four hours, and after forty-eight hours both feet were visibly
      improved. Heparin and analgesics were discontinued. On the ninth hospital day,
      the patient was able to walk and was discharged to home. The innocuous nature of
      the intervention combined with the prompt nature of the therapeutic response
      support a short trial of pentoxifylline in patients with cholesterol emboli who
      are not responding to other therapy.

PMID- 8285388
TI  - Intravascular ultrasound evaluation for assessment and therapeutic decisions in
      aortic diseases.
AB  - Intravascular sonography (IVS) was employed in several aortic pathologies. Acute
      dissecting aneurysm, chronic or recurrent dissection in previously repaired
      aneurysm, iatrogenic (postcatheterism) dissection, noncommunicating dissection
      (mural hematoma), chronic and acute partial thrombosis, and mural fibrosis
      following aspecific aortitis were studied. The stationary and dynamic
      observations combined with angiographic findings provided useful information for
      characterization of the lesions and for therapeutic decisions. In all 14 patients
      studied, supplemental data achieved from IVS suggest that a combination of
      angiography and IVS is the most nearly complete examination for concomitant and
      fast diagnostic workup.

PMID- 8285389
TI  - The value of captopril renal scintigraphy in assessing the results of
      percutaneous transluminal renal angioplasty and in following up renovascular
      hypertension--a case report.
AB  - Percutaneous transluminal renal angioplasty (PTRA) was performed in a patient
      with bilateral renal artery stenoses diagnosed noninvasively by captopril renal
      scintigraphy and confirmed by renal arteriography. The captopril renal
      scintigraphy parameters returned to normal in correlation with improved blood
      pressure response fifteen days after PTRA. Five months later hypertension
      reappeared and the repeated captopril renal scintigraphy suggested left renal
      artery stenosis. PTRA was repeated and a stent was implanted with reversal of
      blood pressure, and captopril renal scintigraphy findings returned to normal
      levels. Six months after second PTRA, the blood pressure increased to
      hypertensive levels, and captopril renal scintigraphy indicated left renal artery
      stenosis. The renal arteriography, however, revealed a new stenosis at the left
      renal artery ostium. The PTRA with a second stent implantation was performed
      successfully. The captopril renal scintigraphic parameters and the blood pressure
      were again normalized after the last intervention and remained normal for
      thirteen months of follow-up.

PMID- 8285390
TI  - Headache, thrombolytic therapy, and chronic subdural hemorrhage--a case report.
AB  - Subdural hematomas are well known but infrequent complications of thrombolytic
      therapy. Although these are usually associated with head trauma, the authors
      describe a case of a patient who received a particularly aggressive thrombolytic
      regimen and presented six months later with complaints of nothing more than a
      headache resistant to medical therapy, without associated neurologic
      manifestations, which was finally diagnosed as a chronic subdural hematoma by
      computerized tomography. In the era of thrombolysis, physicians should maintain a
      heightened index of suspicion for subdural hematoma in patients complaining of
      headache.

PMID- 8285391
TI  - Spontaneous pneumopericardium--a case report.

PMID- 8285393
TI  - Healing and hope brought to thousands at dedication.

PMID- 8285392
TI  - A most unusual case of a whole family suffering from late Lyme borreliosis for
      over 20 years.

PMID- 8285394
TI  - Working to advance health care reform.

PMID- 8285395
TI  - Primary health care: environmental challenges.

PMID- 8285396
TI  - S.C. nurses use carnival to promote good health.

PMID- 8285397
TI  - Nurse participation in CPRI workgroups advances use of computer-based patient
      records.

PMID- 8285398
TI  - ANA testifies on health care reform.

PMID- 8285399
TI  - Nurses are key members of rural interdisciplinary teams.

PMID- 8285400
TI  - Bringing children home for high-tech nursing care.

PMID- 8285401
TI  - The evolution of high-tech nursing.

PMID- 8285402
TI  - A long overdue "welcome home".

PMID- 8285403
TI  - Safeguarding a patient's right to self-determination.

PMID- 8285404
TI  - A day in the life of a nurse. Tenderness and technology are formula for
      successful neo-natal unit.

PMID- 8285405
TI  - Nurses advocate for ethical decision in high-tech care.

PMID- 8285406
TI  - Valuing our staff nurses.

PMID- 8285407
TI  - Privileging essential to APN autonomy.

PMID- 8285408
TI  - N-STAT recruitment up as nurses volunteer for national grassroots network.

PMID- 8285409
TI  - Washington insiders share insights with nurses.

PMID- 8285410
TI  - The 'graying of America'--changing what nurses need to know.

PMID- 8285411
TI  - National Practitioner Data Bank impacts nursing practice.

PMID- 8285412
TI  - Opportunities on the rise in long-term care.

PMID- 8285413
TI  - Providing care to the elderly: a challenge to the health of nursing personnel.

PMID- 8285414
TI  - Workplace, professional issues hinder organizing in long-term care.

PMID- 8285415
TI  - Restraint use still an issue for nurses.

PMID- 8285416
TI  - Staffing nursing homes to meet care needs.

PMID- 8285417
TI  - Meeting mental health needs of the long-term care patient.

PMID- 8285418
TI  - Healing through caring touch.

PMID- 8285420
TI  - Nurses can have impact when families assume caregiver role.

PMID- 8285419
TI  - Compassion part of RN role in long-term care. A day in the life of a nurse.

PMID- 8285421
TI  - House poll shows TB and assault concern to RNs.

PMID- 8285422
TI  - Clinton names nurse as AIDS policy coordinator.

PMID- 8285423
TI  - ANA meets with Dept. of Labor to discuss nurse layoffs.

PMID- 8285424
TI  - The burden of knowing Romania's abandoned children.

PMID- 8285425
TI  - New brochure details measures against sexual harassment.

PMID- 8285426
TI  - Would you recommend your lifestyle to a patient?

PMID- 8285427
TI  - Winners in the transition to reform. As I see it.

PMID- 8285429
TI  - Communication: a critical part of nursing.

PMID- 8285428
TI  - Linking delivery systems will increase early intervention.

PMID- 8285430
TI  - Documentation serves as invaluable defense tool.

PMID- 8285431
TI  - Nursing and risk: the politics of responsibility.

PMID- 8285432
TI  - Looking forward by examining our past.

PMID- 8285433
TI  - Nurses, stand up for nursing home reform!

PMID- 8285434
TI  - Nursing scores big in national media. ANA and nursing issues receiving
      unprecedented coverage.

PMID- 8285435
TI  - Center for Ethics and Human Rights continues consultation, clearinghouse
      activities.

PMID- 8285436
TI  - A day in the life of a nurse. Career changes for public health RN after
      development of new vaccine.

PMID- 8285437
TI  - RNs work against cultural barriers to improve health care access.

PMID- 8285438
TI  - Emphasizing culture diversity to improve nursing education, care.

PMID- 8285439
TI  - Improving patients' lives with pain management.

PMID- 8285440
TI  - Defining 'rural' before tackling access issues.

PMID- 8285441
TI  - FMLA: a first step toward equitable leave policies.

PMID- 8285442
TI  - ANA, Red Cross cite need for more RNs to be trained for disaster relief.

PMID- 8285443
TI  - RNs begin relief efforts in flood-devastated Midwest.

PMID- 8285444
TI  - Just like my cousin Marg, the nurse.

PMID- 8285445
TI  - ANA and its world: an international season.

PMID- 8285446
TI  - Defining cultural and ethnic differences to adapt to a changing patient
      population. As I see it.

PMID- 8285447
TI  - Second licensure? ANA and NCSBN debate the issue.

PMID- 8285448
TI  - [Intra-partum asphyxia and brain damage. Myth and reality].

PMID- 8285449
TI  - [Ultramicroscopic aspects of the lungs in copper-deficient newborn rats].
AB  - In order to investigate the possible morphological alterations in the lungs of
      copper-deficient neonatal rats, three groups of 10 female Sprague-Dawley rats
      were used. The copper-deficient group was fed with a copper-free diet beginning
      at 35 days before pregnancy and throughout the gestation period. The control
      group received a diet adequate in copper and the pair-fed group received a diet
      with adequate copper content, but in limited amounts. After birth, the
      ultrastructural study of the neonatal lungs showed a thickening of the air-blood
      barrier in the copper-deficient group. No other differences were observed in the
      rest of the pulmonary structures.

PMID- 8285450
TI  - [Hemolytic uremic syndrome. Evaluation of clinical and prognostic factors].
AB  - Ten patients with hemolytic uremic syndrome (HUS) were admitted to our ICU during
      the last 7 years. The mean age at entry was 26 month old. Only one child was more
      than 2 years of age. A greater incidence of this illness was noted during the
      summer season. Almost all cases (90%), were severe with arterial hypertension and
      requiring peritoneal dialysis. HUS is a multisystemic disorder with early renal
      involvement, but the possibility of other sites being affected must be kept in
      mind. Half of the patients presented extrarenal manifestations of disease,
      including: seizures (30%), colonic ischemia requiring intestinal resection, and
      heart failure with lung edema due to severe hypertension. The two parameters that
      were helpful in determining the prognosis were the interval of renal
      insufficiency (greater than 14 days) and neurologic impairment, with the later
      being of most importance.

PMID- 8285451
TI  - [Diagnostic value of biliary acid serum levels in Gilbert syndrome].
AB  - OBJECTIVE: The aim of the present work was to study the diagnostic value of the
      measurement of total serum bile acids in patients with Gilbert's syndrome as
      compared to the fasting test. PATIENTS AND METHODS: We have studied 17 patients,
      12 males and 5 females, between the ages of 7 and 15 years. All patients showed a
      slight unconjugated hyperbilirubinemia (1.4 +/- 0.5 mg/dl) in the presence of
      repeated normal liver function test, including the total serum bile acids (7.47
      +/- 2.3 mumol/l), and showed no evidence of hemolysis. A modified fasting test
      was performed in all of the patients. Serum bile acid levels (Merckotest, Merck
      Labs) and the biochemical parameters of liver function were determined before and
      after the fasting test. RESULTS: Our results show that to confirm the diagnosis
      of Gilbert's syndrome, the fasting test could be avoided in patients with
      increased unconjugated bilirubin levels if the basal levels of total serum bile
      acids are normal.

PMID- 8285452
TI  - [Reproducibility of the use of classifications of causes of death in the context
      of inquiries in perinatal mortality].
AB  - The objective of this study was to verify the reliability of the classifications
      of perinatal mortality causes. An independent observer coded the cases of
      perinatal death (n = 152) collected in the Encuesta Confidencial de Mortalidad
      Perinatal de Barcelona (ECMP, Confidential Perinatal Mortality Inquiry of
      Barcelona), by using both the Aberdeen classification system (regarding obstetric
      factors) and the Wigglesworth classification system (according to the initial
      pathological cause), with the same information used previously by the ECMP
      Commission. For the Aberdeen classification, the observed concordance index (Po)
      was 86% and the Kappa coefficient (K) 0.77 (95% CI: 0.68-0.86). For the
      Wigglesworth classification, the figures were 89% and 0.82 (95% CI: 0.74-0.90),
      respectively. The disagreement was mainly due to differences in the
      interpretation of the sequence of death, minimal information available in order
      to classify the cause of death, and misunderstanding of the existing information.
      To a lesser extent, the disagreement was caused by a failure to comply with the
      rules laid down for classifications. The assessment of the causes of death was
      not significantly influenced by birth weight, gestational age, time of death or
      the presence of necropsy. These results support the use of classifications of
      perinatal mortality causes in the context of confidential inquiries.

PMID- 8285453
TI  - [Carbon monoxide poisoning. A home accident to remember].
AB  - BASIS: The aim of this paper is to clinically describe a type of intoxication,
      mainly domestic, which still prevails today and which could even be increasing.
      MATERIALS AND METHODS: We present ten "toxic accidents" which involved seventeen
      patients, all under fifteen years of age. The diagnosis was confirmed upon
      obtaining a level of more than 5% carboxyhemoglobin (CO-Hb) in the blood.
      RESULTS: The symptomatology included: a sensation described by the patients as
      dizziness (53%), headache (53%), nausea and vomiting (35%). Sleepiness, fainting,
      or a faint-like feeling were also frequent (23%). The CO-Hb levels at admission
      were 28.6% +/- 9 (7.1-39.8). Pulse oximetry was performed in three patients,
      resulting in normal values. In all of the cases with the exception of one,
      several members of the family were affected simultaneously and the sources of
      intoxication were the boilers and/or gas heaters that were installed in the
      homes. The exception occurred in a home were there was a traditional coal burner.
      All patients were treated by inhalation of 100% oxygen. This resulted in a mean
      fall of the CO-Hb level in a two-hour interval to 4.6% +/- 2.1 (0-7.8).
      CONCLUSIONS: We emphasis the fact that since the symptoms are often nonspecific,
      a high level of suspicion is necessary in order to make this diagnosis. It is
      fundamental to keep this type of intoxication in mind when various members of a
      family present symptoms simultaneously and especially if it occurs during the
      colder time of the year. Only the determination of the CO-Hb can confirm this
      suspicion since gasometry and pulseoximetry are useless.

PMID- 8285454
TI  - [Quality of life of children with cystic fibrosis].
AB  - Cystic fibrosis is a disease that conveys a large amount of anxiety.
      Nevertheless, it is always said that the psychosocial adaptation of the patients
      and their families is good. In this study, we analyzed the quality of life and
      the knowledge of the illness possessed by parents of 55 children with cystic
      fibrosis. The data obtained suggested a good level of knowledge about the disease
      and an acceptable assessment of their quality of life. The familiar problems
      reflected in the study concerned regular school attendance and the communication
      between parents and patients, mainly concerning the illness. This was more
      obvious with teenagers (12 cases: 21.8%). Finally, it can be stated that the work
      activity and social relationships of the families had changed notably since the
      time of diagnosis (70% of the 55 cases reflect this change), with no differences
      among the age groups. We conclude by stressing the importance of supporting these
      families, especially at the moment of diagnosis. The associations for cystic
      fibrosis are of great importance for preventing psychosocial problems amongst
      their membership.

PMID- 8285455
TI  - [Hyperactivity and infantile depression: a frequent association?].
AB  - We analyzed the scores obtained on the Children Depression Scale (CDS) (1) in a
      group of hyperactive children (n = 39) and a control group (n = 15). We observed
      that there were more children with depression in the hyperactive group (9) than
      in the control group (O). No significant differences appeared in the hyperactive
      index (Conners Teacher Rating Scale) between the depressed hyperactive group
      (DHG) and the non-depressed hyperactive group (HG). No significant correlation
      appeared between the level of hyperactivity and depression. The HG group showed
      no significant difference in their performance on the CDS subtests with respect
      to the control group. However, the results of the "Positive Varios" (PV) subtest
      would indicate the existence of greater feelings of sadness, unhappiness and the
      absence of entertainment in this group.

PMID- 8285456
TI  - [Kawasaki disease; complications and clinical course. Apropos of 38 cases].
AB  - Between January 1978 and December 1991, 38 patients who fulfilled the CDC (Center
      for Disease Control) criteria for Kawasaki syndrome were admitted to our
      hospital. We reviewed the clinical data, laboratory tests, ECG and serial
      echocardiographic studies in order to establish the characteristics of the
      disease in our environment. There were 23 males and 15 females. The age at
      presentation ranged from 4 months to 10 years (mean 3.5 years). Extracardiac
      complications were as follows: arthritis in 12 patients, vesicular hydrops in 2,
      urinary tract infection in 1 and lymphocytic meningitis in 1. Cardiac involvement
      was frequent, with 35% of the patients being diagnosed with coronary pathologies
      (dilatation of coronary arteries in 9 and aneurysm formations in 4). The most
      usual location of these anomalies was in the left main coronary artery. By the
      end to the follow-up period, 71% of the lesions had disappeared. The time
      necessary for this regression was related to the size of the abnormalities. The
      high incidence of cardiac involvement make it necessary to follow these patients
      for a period of time in order to prevent or to treat the later occurring
      sequelae.

PMID- 8285457
TI  - [Nodular antritis and Helicobacter pylori infection in children].
AB  - We have studied 115 patients infected with Helicobacter pylori (HP). Endoscopic
      nodular antritis and histologic lymphonodular hyperplasia was noted. The
      frequency of nodular antritis was compared between the 115 HP patients and a HP
      negative age-matched control group. Nodular antritis was observed in 70.4% of the
      HP-positive patients and 11.3% of the HP-negative group (p <0.001). The
      specificity of nodular antritis was 86.1%. A significant association was found
      between the existence of nodular antritis and histologic lymphonodular
      hyperplasia (67.9%; p < 0.001). In conclusion, the endoscopic nodular antritis is
      a frequent and specific finding in children with HP infection and is associated
      with histologic lymphonodular hyperplasia.

PMID- 8285458
TI  - [Diagnosis of gastroesophageal reflux: ultrasonographic method].
AB  - In this study, 63 infants, 38 males and 25 females, with pathology that suggested
      gastro-esophageal reflux, were studied. These patients were between one month and
      7-1/2 years of age, with a mean age of 29 months and a standard deviation of 28.1
      months. All patients underwent a barium study of the esophagus and the stomach,
      evaluated according to the criteria of Cleveland, an esophageal scintigram to
      detect GER, performed according to the criteria of Fernandez and Arguelles, and
      an abdominal echography according to the technique of Naik and Moore. The test
      was considered a true positive if the echography was positive along with one
      other positive examination. A false positive was considered if only the
      echography were positive. A true negative was when the echography was negative
      along with another negative test. A false negative was when the echography was
      negative and some other test was positive. The following results were obtained
      for the echography: a sensitivity of 68%, a specificity of 84.61% and a safety
      factor of 71.2%. We conclude that echography can be considered as a complimentary
      examination for the study of GER, given it harmless nature, the availability of
      the equipment and the possibility of prolonging the exploration which can be
      recorded on videotape.

PMID- 8285459
TI  - [Intra-articular steroids in chronic juvenile arthritis].
AB  - The use of intraarticular steroids was evaluated in 15 children with chronic
      pauciarticular juvenile arthritis. Of the 25 joints injected, 23 responded
      favorably. At the 6-month check-up, 65% remained in remission. One year after
      injection, 42% maintained a good response. The beneficial effect of the injection
      was not associated with age, sex, erythrosedimentation or arthritis duration. A
      small atrophic lesion in the area of the injection in one patient was the only
      complication.

PMID- 8285460
TI  - [Transcutaneous bilirubinometry: correlation of the reading site obtained with
      spectrophotometry and diazoreaction technique].
AB  - During the last ten years, the clinical use of a non-invasive method for the
      measurement of bilirubin became available as an alternative for classical routine
      procedures. Values obtained with a Minolta bilirubinometer from different reading
      sites were correlated with those obtained by using an optic bilirubinometer
      (American Diagnostics) and a dimethyl-sulfoxide mediated diazoreaction. The
      antero-external face of the thigh revealed the highest correlation coefficients
      with the two serum techniques (r = 0.925, p < 0.001) and was more efficient when
      the newborn was under phototherapy (r = 0.811, p < 0.01).

PMID- 8285461
TI  - [Leri-Weill dyschondrosteosis. Report of a new familial case].

PMID- 8285462
TI  - [Discordant acquired immunodeficiency syndrome in dizygotic twins].

PMID- 8285463
TI  - [Acute hemorrhagic edema in an infant].

PMID- 8285464
TI  - [Turner syndrome associated with dychondrosteosis].

PMID- 8285465
TI  - [Bilateral cataract in the initial phase of insulin dependent diabetes mellitus
      in childhood].

PMID- 8285466
TI  - [Joubert syndrome without mental retardation].

PMID- 8285467
TI  - [Acute carbon monoxide poisoning. Importance of diagnosis. Report of 3 pediatric
      cases].

PMID- 8285468
TI  - [Sepsis caused by Hemophilus influenzae type B in a neonate].

PMID- 8285469
TI  - [Fatal wounding by a compressed air weapon].

PMID- 8285470
TI  - [Usher syndrome and possible heredity linked to X chromosome].

PMID- 8285471
TI  - [Holt-Oram syndrome. Report of a case].

PMID- 8285472
TI  - [Cutis verticis gyrata in a newborn infant].

PMID- 8285473
TI  - [Larsen syndrome and idiopathic hypercalciuria].

PMID- 8285474
TI  - [Intrafamilial psychological violence: opportunity to consider judicial aspects].

PMID- 8285475
TI  - [The correlation between successful nuclear status to maternal status in the
      psychological development of the child].

PMID- 8285476
TI  - [Specifics of therapeutic consultation with the child and his parents].

PMID- 8285477
TI  - [Tragedy of two fates].

PMID- 8285478
TI  - [Children of alcoholic parents. A clinical study].

PMID- 8285479
TI  - [Indications for hospitalization: a topic for collaboration between the child
      psychiatrist and the family].

PMID- 8285480
TI  - [Jean-Pierre, replacement child or unfounded suspicion].

PMID- 8285481
TI  - [Disorders in the immigrant child and family crisis].

PMID- 8285482
TI  - ["My son has a problem in the head". "My daughter has a flawed head, a flawed
      character". What is the relationship to ethnopsychiatry?].

PMID- 8285483
TI  - [Mother-child relationship: the kangaroo syndrome].
AB  - The author describes among some adults a special clinical form of mother-child
      relation in which bond between both partners, without being fusional, remains
      very strong and can be likened with the larva relation among marsupials. He calls
      to mind the hard therapeutic problems given by persistency at adult age of this
      complementary type relation.

PMID- 8285484
TI  - [Separation anxiety disorder and aggression in the child].

PMID- 8285485
TI  - [The family as a group].

PMID- 8285486
TI  - [The family impaired with incest].

PMID- 8285487
TI  - [Pathology of post-adolescence and early adulthood. Role of the parental
      function].
AB  - That study views a developing perspective and touches on the end of the
      adolescence like a crucial time during that the subject, often remained in a kind
      of latency from the beginning of his adolescence delay his entry in the adult
      world. As a result certain particularities of the psychological functioning
      peculiar to that period and a pathology of 18-25 years considered in the
      incidence of the failures during the processus of separation-individuation,
      beginning in the infancy, and has to draw to close. Different situations are
      considered concerning the role of the parents, and the therapeutic perspectives
      implicating the families.

PMID- 8285488
TI  - [Place of the long-term treated psychotic in the family of the psychiatrist].

PMID- 8285489
TI  - [Strategy of clinical intervention in families of alexithymic patients].
AB  - Authors study psychiatric symptoms coexisting with psychosomatic disorders and
      artistic behaviours, in alexithymia. Building genealogy brings informations on
      their family system, and opens way to psychotherapeutic treatment.

PMID- 8285490
TI  - [The immigrant family in psychiatry].

PMID- 8285491
TI  - [Development of a new therapeutic approach to migrant families. Reflections from
      consultation experience in ethnopsychiatry].

PMID- 8285492
TI  - [Difficult separations and reunions].

PMID- 8285493
TI  - [The family with reference to prescription of psychotropic drugs to the child and
      adolescent].

PMID- 8285494
TI  - [Group psychotherapy for families of psychotic patients].

PMID- 8285495
TI  - [Reactions of the child and the therapist as therapeutic tools in focal family
      therapy].

PMID- 8285496
TI  - [Psychiatric aspects of cancer diagnosis].

PMID- 8285497
TI  - [Descriptive study of schizophrenic patients treated for 15 years in the
      psychiatric department B of the Clermont-Ferrand C.H.U].

PMID- 8285498
TI  - [The elderly schizophrenic patient].

PMID- 8285499
TI  - [Specifics of various forms of paranoia and paraphrenia].

PMID- 8285500
TI  - [New diagnostic criteria of deficits in schizophrenia by the Carpenter school:
      importance and validity].

PMID- 8285501
TI  - [Evolution of schizophrenia: role of symptomatology in the reliability of 11
      diagnostic systems for schizophrenia].

PMID- 8285502
TI  - [Predictive factors in the evolution of schizophrenia. Relations with
      neurodevelopmental models].

PMID- 8285503
TI  - [Neuro-imaging in schizophrenia].

PMID- 8285504
TI  - [A psycho-educational and cognitive approach to the treatment of adolescent
      schizophrenic patients. Results of two years of treatment].

PMID- 8285505
TI  - [Care and rehabilitation of patients with schizophrenia with an unfavorable
      course].

PMID- 8285506
TI  - [Satellite care of schizophrenic patients].

PMID- 8285507
TI  - [Resistant schizophrenia. Definition of a clinical approach and therapeutic
      strategy. Nosologic consequences for the concept of schizophrenia].

PMID- 8285508
TI  - [Hospitalization time, therapeutic work and transitional structures].

PMID- 8285509
TI  - [Importance and limits of combined care for psychotic states in the acute phase].

PMID- 8285510
TI  - Multivariate predictors of audiological success with multichannel cochlear
      implants.
AB  - To predict the audiological outcomes of 2 multichannel cochlear implants, a
      preoperative battery of historical, audiological, electrophysiologic, and
      psychologic variables from 48 postlingually deafened adults was tested in a
      prospective randomized clinical trial. Multivariate analyses were used to select
      and combine these preoperative variables in a predictive index that was
      significantly related to audiological outcome at 9 months. The preoperative
      variables included in the predictive index were duration of profound deafness,
      speech reading ability, residual hearing, cognitive ability, measures of
      compliance and engagement with treatment, and use of nonverbal communication
      strategies. The preoperative predictive index had correlations of .81 with the
      Iowa Sentences Test, and .78 with the NU-6 word understanding scores, both
      obtained in a sound-only test. Probability and percentile curves generated from
      these data offer considerable optimism in forecasting the range of likely
      audiological outcomes that would be realized by postlingually deafened adult
      candidates for multichannel cochlear implants.

PMID- 8285511
TI  - Aneurysmal bone cyst of the mandible.
AB  - The aneurysmal bone cyst is a nonmalignant lesion that by expanding disrupts the
      architecture of the affected bone and destroys surrounding tissue. Developing
      rarely in the craniofacial region, and more commonly affecting the long bones and
      the spine, the lesion has characteristic radiographic features but is
      definitively diagnosed only by pathologic characteristics. Complete surgical
      excision is used to treat aneurysmal bone cyst, with either curettage or
      composite resection. Recurrence is common in incompletely excised lesions.
      Adjunctive cryotherapy reduces the risk of recurrence, and radiotherapy is
      reserved for nonresectable lesions. The case we report of a young man seen for a
      large mandibular aneurysmal bone cyst demonstrates the complexity of diagnosing
      and treating this condition.

PMID- 8285512
TI  - Rhinophyma: a new approach to hemostasis.
AB  - Rhinophyma is a benign tumor of the nose. It possesses both functional and
      cosmetic implications. The pathophysiology of the disease is reviewed to
      illustrate the basis for the treatment options. Many different therapeutic
      modalities have been reported in the literature, each with reasonable success. A
      new treatment approach to this condition is developed using a combination of the
      Weck blade and the argon beam coagulator. This modality is found to be relatively
      simple and less traumatic than all the other techniques used by the senior
      author.

PMID- 8285513
TI  - Location of the preepiglottic space and its relationship to the paraglottic
      space.
AB  - An investigation was carried out to determine the location of the preepiglottic
      space (PES) and its relationship to the paraglottic space (PGS). Excised human
      adult larynges served as materials for this study. The distribution of the PES of
      the larynx was determined histologically in 3 whole organ serial sections:
      sagittal, horizontal, and coronal. The results are summarized as follows. 1) The
      PES exists not only anterior, but also posterolateral and inferolateral to the
      epiglottis. 2) Its posterior end is located in the vicinity of the
      anteroposterior midpoint of the thyroid lamina. 3) The PES is adjacent to the PGS
      posteroinferiorly and is separated by fibrous tissue (the thyroglottic ligament).
      Posterosuperiorly, the 2 spaces are not clearly delineated from each other.

PMID- 8285514
TI  - Experimental tracheal tube created with vascularized fascia.
AB  - An experimental fascial transferable bed was developed in the rabbit model. This
      tissue is reliable in bringing a viable mucosal graft inside the larynx. A
      vascular connective tissue sheet with full-thickness mucosa and autogenous
      cartilage for external support are needed. In this study a tracheal tube was
      preformed to study the use of autogenous cartilage as support for a
      circumferential lumen.

PMID- 8285515
TI  - Airway protection during breath-holding.
AB  - Little is known about laryngeal function during breath-holding. The completeness
      of laryngeal closure during breath-holding is clinically relevant during the
      supraglottic swallow. To investigate this phenomenon, vocal cord position was
      studied prospectively in 10 adults during breath-holding using nasolaryngoscopy
      with video recording. The position of the vocal cords was not consistent during
      breath-holding. Some subjects closed the glottis, while others had variable
      amounts of glottic opening. Straining and vocalizing at the onset of breath
      holding produced both glottic and supraglottic closure, increasing the number of
      levels of laryngeal closure during breath-holding. Nasolaryngoscopy can be used
      clinically to document the airway protection, the effects of various protective
      maneuvers, and any resulting aspiration during breath-holding and during the
      supraglottic swallow.

PMID- 8285516
TI  - Late waves in the response recorded from the intracranial portion of the auditory
      nerve in humans.
AB  - We showed in previous studies that the click-evoked responses from the exposed
      eighth nerve in some patients contain quasi-periodic components that appear in
      the interval between 4 and 16 milliseconds after the click stimulus, and that the
      phase of these oscillatory components reverses when the click polarity is
      reversed. When the responses to clicks of opposite polarity are subtracted from
      each other, these late waves appear as a prolonged quasi-periodic oscillation
      with a frequency around 700 Hz. These late components appear more frequently in
      patients with high-frequency hearing losses than in patients with normal hearing.
      We have attributed these components to prolonged and in-phase oscillations of a
      large portion of the basilar membrane, possibly caused by the generation of
      standing waves on the basilar membrane. The results of the present study show
      that these oscillations correspond closely in both frequency and phase to the
      late oscillations that are seen in the cross-correlograms of the responses from
      the exposed eighth nerve to pseudorandom noise. The finding that similar quasi
      periodic components can be retrieved from the responses from the exposed eighth
      nerve to both transient and continuous sounds is taken as an indication that the
      neural activity that these components represent reflects some general property of
      the cochlear frequency analyzer. We also found that the speech discrimination is
      not noticeably different in patients with such waves compared with what it is in
      patients with similar hearing loss who do not have such waves. This is taken as
      an indication that spectral analysis in the cochlea is less important in speech
      discrimination than previously assumed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285518
TI  - Extracranial carotid artery aneurysm.
AB  - Although rare, extracranial carotid aneurysms are common enough to be considered
      in the differential diagnosis of a mass in the neck or posterior pharynx. The
      unexpected finding of an aneurysm of the carotid artery during the biopsy of a
      mass in the neck for histologic diagnosis could be catastrophic. The case
      presented demonstrates the importance of diagnostic imaging of the neck prior to
      biopsy of a clinically presumed solid mass.

PMID- 8285517
TI  - Arachidonic acid metabolites in experimental otitis media and effects of anti
      inflammatory drugs.
AB  - Previous studies have shown that arachidonic acid (AA) metabolites are important
      in the pathogenesis of otitis media with effusion. The AA metabolites in 4
      different experimental models for otitis media were analyzed, and the effect of
      anti-inflammatory drugs was studied. Purulent otitis media was induced in rats by
      inoculation of Streptococcus pneumoniae in the tympanic bulla, serous otitis
      media by blocking the tympanal orifice of the eustachian tube, and mucoid otitis
      media by combining the two procedures. Middle ear effusion was also induced by
      stimulating the external auditory canal with cold air. Indomethacin and
      hydrocortisone were used to inhibit AA metabolism in the latter model.
      Lipoxygenase products dominated in the purulent and cold air otitis media models.
      Cyclooxygenase products dominated in the mucoid and serous models. Indomethacin
      inhibited accumulation of middle ear effusion in the cold air otitis media model,
      whereas hydrocortisone did not. Apart from AA metabolites, other mechanisms and
      mediators appear to be responsible for the increased vessel permeability observed
      in the cold air otitis media model, such as interactions between mast cells and
      nerves in the middle ear mucosa.

PMID- 8285519
TI  - Tortuous internal carotid artery: a rare cause of oropharyngeal bulging diagnosed
      by magnetic resonance angiography.

PMID- 8285520
TI  - Extracranial, extraspinal meningiomas of the head and neck.
AB  - The head and neck is the most frequent location for extraneuraxial meningiomas,
      be they wholly extracranial or extraspinal or extensions of central nervous
      system meningiomas. Regardless of anatomic site of origin, nearly all meningiomas
      arise from meningocytes of arachnoid granulations. Ectopic arachnoid cell
      clusters have a predilection for areas of dural penetration of cranial nerves,
      and it is in these areas that most extracranial meningiomas are found. Surgical
      excision is the mainstay of treatment and must be planned by radiologic studies
      to determine the extent of the tumor and the presence or absence of a companion
      central nervous system meningioma. The often locally invasive and aggressive
      behavior of the meningiomas belies their benign histologic appearance.

PMID- 8285521
TI  - Rare congenital anomaly of tracheal agenesis (TA)

PMID- 8285522
TI  - The expanded "BAT" flap for treatment of male pattern baldness.
AB  - A new combination of expanded simultaneous transposition and advancement flaps is
      reported for the treatment of extensive male pattern baldness. Although vertical
      transposition and parieto-occipital advancement flaps in themselves are not new,
      their combination and simultaneous bilateral use combined with the use of
      expansion is new. The advantages of the expanded bilateral advancement
      transposition flap procedure are presented, along with the technique and results.
      The results are predictable, providing a more pleasing result, with a natural
      immediate temporal recession, avoidance of temporal dog-ears, and desirable
      anterior-superior direction of hair growth. Although flaps do require surgical
      skill and training, and there are risks and possible complications involved, the
      results are achieved in a relatively short time compared with grafting
      techniques. Flaps also provide the advantages of a full and natural hairline
      contrasted with the sparse look afforded by multiple grafts. The described
      procedures are very effective and reliable when properly planned and properly
      executed.

PMID- 8285523
TI  - Restoring the breast to match the normal side.
AB  - Although breast symmetry is for most patients a reconstructive goal of the
      highest order, the alteration of a normal breast may, for many women, constitute
      another "branding." Our patients have chosen overwhelmingly to leave their normal
      breasts "untouched" since having been given the opportunity to do so. Treatment
      planning and surgical methods are described that have made possible symmetrical
      results without change in the normal breast. Representative patients are shown to
      document the usefulness of these plans in women of varied anatomy. Our ongoing
      experience shows us that it is an uncommon patient, indeed, for whom symmetrical
      breast restoration cannot be accomplished without resorting to surgery on the
      normal organ.

PMID- 8285524
TI  - Reconstruction of radiation-induced chest wall lesions.
AB  - Radiation-related ulcers of the chest wall provide a great challenge to
      reconstructive surgeons because of the necessity of protecting the underlying
      vital structures and the difficulty in repairing irradiated tissues. To evaluate
      the efficacy of treatment, 24 patients who underwent reconstruction of radiation
      related ulcers of the chest wall were retrospectively reviewed. A variety of
      muscle and musculocutaneous flaps as well as omentum and microvascular tissue
      transfers were used to reconstruct these defects. The defects in the chest wall
      arose from spontaneous breakdown of irradiated tissue, tumor recurrence, or
      nonhealing after surgical procedures performed in the irradiated field. Our
      treatment protocol consisted of aggressive debridement of all affected tissues
      including skeletal tissues when necessary. The application of a tension free
      closure using a flap was then performed. Skeletal support was provided in three
      reconstructions. There were no mortalities, the morbidity rate was 29% (six
      minor, one major complication), and the mean hospital stay was 10.9 days. None of
      the patients required prolonged ventilator support. In all but 2 patients, who
      were left with small chronic granulating nonhealing wounds, complete wound
      healing was achieved. We conclude that chest wall reconstruction of radiation
      related ulcers can be achieved with minimal morbidity in an acceptable period of
      inpatient hospital care using a variety of vascularized tissue transfers.

PMID- 8285525
TI  - Acrylic splints for dental alignment in complex facial injuries.
AB  - Twenty-four patients with complex facial injuries were managed by wide
      subperiosteal exposure, precise anatomical reduction, rigid internal fixation,
      and immediate bone grafting when indicated, in conjunction with dental
      impressions, model surgery, and fabrication of dental splints to establish proper
      preinjury occlusion. The study population consisted of 18 men and 6 women, whose
      ages ranged from 18 to 49 years (mean, 30.7 yr) at the time of injury. High
      velocity motor vehicle accidents were responsible for facial injuries in 18
      patients, gunshot wounds in 2, low velocity blunt trauma in 3, and falls in 1.
      All facial fractures involved the occlusion, and unstable and/or comminuted
      palatal/maxillary and mandibular fractures, often with edentulous segments, were
      the major indications for fabrication of acrylic splints. Depending on the nature
      of the fracture pattern, model surgery was performed on the maxillary and/or
      mandibular models and segmented along fracture lines. These fragments were then
      repositioned according to dental wear facets and preinjury occlusion. When
      possible, preinjury occlusal records were obtained before splint fabrication.
      Models were mounted on a Galetti articulator and palatal, lingual, and/or
      occlusal splints were fabricated. Edentulous segments were compensated for by
      local buildup of the splints to produce an occlusal stop. Arch bars were fixed
      directly to the splint with acrylic. Twenty-six splints were used in the 24
      patients to establish proper occlusal relationships before internal fixation of
      fractures. The types of splints were palatal (n = 8), palatal-occlusal (n = 6),
      lingual (n = 8), lingual-occlusal (n = 1), and occlusal (n = 3).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8285526
TI  - Long-term results after surgical reduction cheiloplasty in patients with
      Melkersson-Rosenthal syndrome and cheilitis granulomatosa.
AB  - Cheilitis granulomatosa in patients with Melkersson-Rosenthal syndrome has proven
      difficult to treat, and various forms of symptomatic treatment of orofacial
      swellings have been used with varying success. To evaluate long-term results
      after surgical reduction cheiloplasty in patients suffering from persistent lip
      swellings, a follow-up study was performed on 13 patients after 16 years
      (median). The operations were performed after unsuccessful conservative treatment
      and regardless of disease activity. Pre- and postoperative medical histories were
      updated and a clinical examination evaluated the following criteria for a good
      result: symmetry of the lip, a normalized anterior projection, dimensional
      harmony between upper and lower lip, no disfiguring cicatrices, and no sensory
      disturbances. In spite of postoperative disease activity in 6 patients, all 13
      patients were satisfied with the long-term result. Clinically, the results in 12
      patients were considered good. We therefore recommend lip resection as described
      when a stationary swelling becomes associated with permanent aesthetic deformity
      or functional disturbances and conservative measures are unsuccessful.

PMID- 8285527
TI  - Effect of insulin-like growth factor-1 on zygomatic arch bone regeneration: a
      preliminary histological and histometric study.
AB  - A number of physicians have attempted to pharmacologically manipulate the healing
      of bony fractures with a variety of agents such as growth hormone, thyroxine,
      chondroitin sulfate, and parathyroid hormone. Thus far, results from these
      experiments have been inconclusive. Previous research dealing with insulin-like
      growth factors has centered on cultures of osteoblast-like cells and has
      demonstrated a stimulatory effect on bone collagen synthesis, which may in fact
      play a critical role in the process of bone formation itself. The purpose of this
      investigation was to examine the effects of a genetically engineered growth
      factor, insulin growth factor type I, on midfacial fracture healing. In 24 adult
      male Sprague-Dawley rats, a standardized defect was created within the midportion
      of each zygomatic arch. One-half were treated with insulin growth factor type I
      administered with an osmotic infusion pump and the other half served as control
      subjects. At 2, 4, 8, and 12 weeks, animals from each group were killed and
      specimens of the defect obtained. Data were collected from radiographs and
      histological studies to compare the extent of bony repair. From this study, it
      appears that insulin growth factor type I could exert a potentiating effect on
      the repair of midfacial bone defects.

PMID- 8285528
TI  - The effects of insulin-like growth factor-1 on critical-size calvarial defects in
      Sprague-Dawley rats.
AB  - In a previous study prepared in 1992, we found that insulin-like growth factor-1
      showed promise in hastening intramembranous bone repair in midfacial bone
      defects. For the present study, we created critical-size calvarial defects in 36
      adult male Sprague-Dawley rats. The rats were then divided into two groups and
      killed at 1, 2, 3, 4, 5, 6, and 8 weeks. Twenty-one rats were administered
      insulin-like growth factor-1 subcutaneously with a 14-day osmotic infusion pump.
      An untreated group served as controls. Results were compared using routine
      histology to examine bone reconstitution of the surgical defects. Within the
      experimental group, we observed repair commenced at approximately 1 week and the
      critical-size calvarial bone defects were completely obliterated by 6 weeks; in
      the control group, even by 8 weeks, the surgical defects remained almost
      unchanged. In summary, this is further evidence that insulin-like growth factor-1
      may have the potential to accelerate repair of intramembranous bone defects.

PMID- 8285529
TI  - Microvascular reconstruction of the esophagus with pedicled small intestine.
AB  - A modified procedure for total reconstruction of the esophagus with small
      intestinal transfer is suggested. It includes reconstruction of marginal and
      lymphatic vessels of its mesentery using microsurgical technique. With
      application of the modified procedure, the transplant may be longer, its loops
      may be straightened and better vascularized, and lymphatic drainage of the
      intestine may be preserved.

PMID- 8285530
TI  - Microvascular free transfer in reconstruction of the pharynx and cervical
      esophagus.
AB  - We present 8 cases of microvascular reconstruction of the pharynx and cervical
      esophagus using 5 free ileal transfers and 3 radial forearm flaps. One of the
      skin flaps underwent a delay procedure a month before transfer. All flaps
      survived, though there were 2 salivary fistulas that healed spontaneously.

PMID- 8285531
TI  - A method for optimizing skin graft healing and outcome of wounds of the penile
      shaft and scrotum.
AB  - Split-thickness skin grafting provides the best functional and aesthetic result
      in the treatment of wounds of the penis and scrotum. Achieving graft adherence
      and take in this anatomically mobile region is challenging. A simple method of
      effectively stabilizing skin grafts in the treatment of penile and perineal
      wounds is described, and patients in whom complete graft take was achieved are
      discussed.

PMID- 8285532
TI  - Massive orbital teratoma in the newborn.
AB  - Teratomas are rare germ cell tumors that comprise approximately 1% of orbital
      tumors in childhood. Review of the world literature revealed only 51 well
      documented patients with true congenital orbital teratomas. We present a newborn
      girl with a massive orbital teratoma that caused significant orbital enlargement
      with inferior and lateral displacement of the zygoma and a thinning of the
      orbital roof. The ipsilateral maxilla and palate were depressed inferiorly. No
      bony invasion was seen despite its massive size. A craniofacial approach was used
      to safely and completely extirpate this tumor. Histological sections demonstrated
      derivatives of all three germ cell layers. Recommendations for definitive
      treatment and a review of the literature are presented.

PMID- 8285533
TI  - Secondary reconstruction of abdominal wall defects associated with exstrophy of
      the bladder.
AB  - Exstrophy of the bladder is a spectrum of congenital anomalies that involve the
      structures of the lower abdominal wall. The classic bladder exstrophy results in
      a severe deformity. The purpose of the original surgery is to obtain a secure
      abdominal wall closure with urinary continence. In present times the abdominal
      wall is repaired shortly after birth. The occasional patient has residual
      anatomical deformities that impede their social development and interaction.
      Secondary reconstructive surgery can be helpful, and this patient report
      illustrates this.

PMID- 8285534
TI  - Correction of prominent zygomata by tripod osteotomy of the malar bone.
AB  - Reduction of the prominent zygomata is occasionally required in aesthetic surgery
      in Oriental patients. Two approaches to surgical exposure are commonly used; one
      is oral and the other is coronal. In addition, there are two basic surgical
      concepts of reduction malar-bone plasty; one is thinning and chiseling the
      prominent area, and the other is mobilizing the prominent zygoma by osteotomy of
      the zygomata. We devised a new tripod osteotomy of the zygomata by the coronal
      exposure approach and applied it to correct prominent zygomata in association
      with frontoperiorbital lifting in Oriental patients. Satisfactory results were
      obtained and we concluded that this was an effective procedure to correct
      prominent zygomata for elderly Oriental patients.

PMID- 8285535
TI  - Revascularization of an ischemic replanted thumb using a lateral arm free fascial
      flap.
AB  - Digital ischemia and cold sensitivity after replantation are common. Occasionally
      they are severe enough to warrant intervention, including amputation of an
      otherwise functional digit. We present a patient with pregangrenous ischemia in a
      replanted thumb 10 years after multiple digit replantation. Angiography revealed
      vascular occlusion in the distal radial artery with no patent vessel in the
      thumb. The option of transposition of a spare neurovascular bundle from the
      adjacent radial digits was limited by their single-vessel supply resulting from
      previous replantation. We describe a method of revascularization by introduction
      of an arteriovenous pedicle, using a free fascial flap harvested from the lateral
      arm and based on terminal ramifications of the profunda brachii vessels. The flap
      was buried between the pulp and flexor tendon sheath and anastomosed to the
      radial artery and a wrist vein. This resulted in successful revascularization of
      the digit, clinically and radiologically, and 20 months later, the patient
      remains symptom free.

PMID- 8285536
TI  - Pseudocyst of the auricle: case reports and its biochemical characteristics.
AB  - Pseudocyst of the auricle is a rare, asymptomatic cystic swelling of the auricle
      resulting from accumulation of yellow viscous fluid with unknown cause. We herein
      report 3 such patients in whom biochemical study of the aspirated fluid revealed
      markedly elevated activity of lactate dehydrogenase (LDH) and a preponderance of
      LDH-4 and LDH-5. We postulate that pseudocyst formation is due to the disruption
      of the auricular cartilage and that LDH in the fluid is released from the
      auricular cartilage. This observation supports that the lesions represent a
      pattern of chondromalacia. It is hypothesized that the cause of such pseudocysts
      is repeated minor trauma.

PMID- 8285537
TI  - Experience with U-shaped gluteal thigh flap for reconstruction of radionecrosis
      in the sacral region.
AB  - The gluteal thigh flap first reported by Hurwitz in 1980 can provide a large
      reliable flap for coverage of the sacrogluteal and perineal regions. This flap
      can be extended quite some way along its axial inferior gluteal vessels, but its
      width is limited to approximately 10 cm if direct approximation of the donor site
      defect is required. In this article, we report a U-shaped modification of the
      gluteal thigh flap for efficient use of the flap in covering a large defect in
      the sacrogluteal region.

PMID- 8285538
TI  - The racket over numbers.

PMID- 8285539
TI  - Laparoscopic vagotomy: an operation for the 1990s?

PMID- 8285541
TI  - Markers of data quality in computer audit: the Manchester Orthopaedic Database.
AB  - This study investigates the efficiency of the Manchester Orthopaedic Database
      (MOD), a computer software package for record collection and audit. Data is
      entered into the system in the form of diagnostic, operative and complication
      keywords. We have calculated the completeness, accuracy and quality (completeness
      x accuracy) of keyword data in the MOD in two departments of orthopaedics
      (Departments A and B). In each department, 100 sets of inpatient notes were
      reviewed. Department B obtained results which were significantly better than
      those in A at the 5% level. We attribute this to the presence of a systems
      coordinator to motivate and organise the team for audit. Senior and junior staff
      did not differ significantly with respect to completeness, accuracy and quality
      measures, but locum junior staff recorded data with a quality of 0%.
      Statistically, the biggest difference between the departments was the quality of
      operation keywords. Sample sizes were too small to permit effective statistical
      comparisons between the quality of complication keywords. In both departments,
      however, the poorest quality data was seen in complication keywords. The low
      complication keyword completeness contributed to this; on average, the true
      complication rate (39%) was twice the recorded complication rate (17%). In the
      recent Royal College of Surgeons of England Confidential Comparative Audit, the
      recorded complication rate was 4.7%. In the light of the above findings, we
      suggest that the true complication rate of the RCS CCA should approach 9%.

PMID- 8285540
TI  - Lymphocele.
AB  - Lymphocele is a complication which will be familiar to the gynaecological
      surgeon, particularly the oncologist. It is also well recognised in association
      with urological pelvic surgery and renal transplantation. Occurrence of
      lymphocele has been described in relation to surgery in a wide variety of other
      areas including the mediastinum, axilla, neck, aorta and peripheral vasculature.
      Clearly many of these examples are unusual occurrences, but they serve to
      illustrate that this complication will be encountered occasionally by surgeons in
      any of a number of disciplines.

PMID- 8285542
TI  - Cell proliferation, tumour growth and clinical outcome: gains and losses in
      intestinal cancer.

PMID- 8285543
TI  - Bile reflux in columnar-lined Barrett's oesophagus.
AB  - Total and individual bile acid concentrations in the oesophageal aspirates from
      30 patients with Barrett's oesophagus were compared with those from 15 patients
      with oesophagitis and 15 normal subjects. The highest total bile acid
      concentrations were found in the Barrett's patients and this was statistically
      significant when compared with controls but not oesophagitis patients. However,
      when the 95th percentile value of bile acid concentration in the normal subjects
      was taken as the 'cut-off' level, a significantly higher number of Barrett's
      patients (15/30) were bile refluxers than were the oesophagitis patients (3/15).
      Glycocholic and taurocholic acids were the predominant bile acids detected, but
      taurochenodeoxycholic acid was also present in significant amounts in the
      patients with oesophagitis. It is possible that bile reflux contributes to the
      development of Barrett's oesophagus.

PMID- 8285544
TI  - Closing the audit circle: effect of continuing audit on arthroscopic practice.
AB  - A prospective study in a single orthopaedic unit for one calendar year was
      carried out to examine the effect of continuing audit on arthroscopic practice. A
      standard proforma was introduced to record information and results were analysed
      using a system of audit codes. Two audit periods were examined, the first 3
      months and the subsequent 9 months. Results after audit of the first period were
      compared with the second period; diagnostic accuracy and clarity had improved as
      had the accuracy of audit coding. The subset of patients with a preoperative
      diagnosis of a meniscal tear was analysed and the diagnostic accuracy for this
      group improved over the year. We found that the Audit Circle had been closed in
      the areas of diagnostic clarity, diagnostic accuracy of meniscal tears and the
      accuracy of audit coding.

PMID- 8285545
TI  - Does teaching audit improve standards, and affect MCQ results in undergraduate
      trauma and orthopaedic tuition?
AB  - Over the study period from 1981 to 1987 inclusive, student critiques were scored
      to indicate the undergraduates' perception of the quality of teaching they
      received on each 2-month attachment to the trauma and orthopaedic surgical
      departments of two teaching hospitals. The medical staff and the environment in
      the two teaching hospitals were different. It was found that while the mean MCQ
      results did not change significantly throughout the study period, an improvement
      was noticed in the perceived quality of undergraduate tuition, especially at one
      hospital.

PMID- 8285546
TI  - Comparison of the cost-effectiveness of administering heparin subcutaneously or
      intravenously for the treatment of deep vein thrombosis.
AB  - The cost-effectiveness of subcutaneous heparin (20,000 iu, twice daily, prefilled
      syringes), a continuous intravenous infusion of 24,000 iu heparin in 24 h, and
      the intravenous infusion of 48,000 iu heparin as two consecutive 12-h infusions
      of 24,000 iu, were compared. The costs were calculated by timing and observing
      staff in three hospitals, and by noting the costs of what they used. Cannulation
      of a vein by a doctor took a mean of 4 min 16 s and cost 2.61 pounds. To prepare
      and administer the 24,000 iu of heparin in a 24-h infusion took a mean of 22 min
      42 s/day and cost 9.52 pounds. If a 48,000 iu in 24-h infusion was used it took a
      mean of 36 min 3 s/day and cost 16.81 pounds. The use of heparin syringes, 20,000
      iu subcutaneously twice daily, took 2 min 53 s/day and cost 4.80 pounds. A
      generic cost formula was calculated to allow for variation in staff or drug
      costs. The subcutaneous and intravenous routes were assumed to be equally
      effective on the basis of the medical literature. This study shows that
      subcutaneous heparin therapy is significantly more cost-effective than
      intravenous heparin therapy. The reduction in cost and liberation of nursing time
      mean that the subcutaneous route should be preferred.

PMID- 8285547
TI  - Outcome of biliary tract surgery in unknown cirrhotics: a case-control study.
AB  - The substantial risk of biliary surgery in patients with liver cirrhosis may be
      reduced by preoperative preparation but the problem of the unknown cirrhotic
      remains. We studied 18 patients found incidentally to have cirrhosis at surgery.
      The perioperative complications and the outcome in these patients was compared
      with 18 non-cirrhotic patients, computer matched for age and sex, undergoing the
      same operations. Mean blood loss at operation was 324 ml (SD 218.1 ml) in the
      cirrhotic group and 105 ml (SD 74.7 ml) in the control group (P < 0.01). The
      postoperative complication rate was 38% in cirrhotics, but zero in controls (P <
      0.01). The length of hospital stay was significantly increased in the cirrhotic
      group (P < 0.01). There was no mortality in either group. The incidental finding
      of cirrhosis at biliary surgery is associated with increased peroperative
      bleeding and increased morbidity. There is no increase in mortality in such
      patients.

PMID- 8285548
TI  - Intraperitoneal bupivacaine for effective pain relief after laparoscopic
      cholecystectomy.
AB  - Laparoscopic cholecystectomy is now widely practised. There are various methods
      of pain relief used but none has been assessed or compared following this
      procedure. We have assessed the analgesic effect of intraperitoneal bupivacaine
      in laparoscopic cholecystectomy. Sixty consecutive patients were randomly
      assigned to one of two groups. Patients in group 1 were given 20 ml of saline
      injected under vision into the region of the gallbladder bed. Patients in group 2
      were given 20 ml of 0.25% bupivacaine in a similar fashion. Postoperative pain
      was assessed with a visual analogue pain scale and the site of pain was recorded.
      Patients in the bupivacaine group had less pain in the early postoperative period
      and a lower incidence of pain in the right hypochondrium. Intraperitoneal
      bupivacaine is a simple and effective treatment for postoperative pain after
      laparoscopic cholecystectomy.

PMID- 8285549
TI  - A simple technique of umbilical port closure in laparoscopic cholecystectomy.

PMID- 8285550
TI  - An emergency daytime theatre list: utilisation and impact on clinical practice.
AB  - A prospective study of all weekday emergency surgery performed in a district
      general hospital over an 18-month period was undertaken to assess the impact of a
      fully staffed, daytime operating theatre for emergency surgery on night-time
      operating and on consultant supervision of trainees. In the 12 months following
      the introduction of the emergency list there was a 46% reduction in the number of
      general surgical operations performed after midnight compared with the preceding
      6 months. Despite the increase in daytime operating the degree of consultant
      participation was unchanged, with the majority of emergency procedures being
      performed by unsupervised junior surgeons and anaesthetists. Although the
      emergency theatre was available to all specialties and was used for 'scheduled'
      and occasional 'elective' cases when there were no emergencies, only 37% of total
      theatre time was used. Without a change in consultant workload and practice which
      permits their increased involvement in emergency surgery, a dedicated daytime
      emergency theatre may be a costly measure which fails to fulfil all CEPOD
      recommendations.

PMID- 8285551
TI  - Lower limb ischaemia in the octogenarian: is limb salvage surgery worthwhile?
AB  - Vascular surgeons are being asked to manage vascular disease in an increasingly
      elderly population, and advanced age may be considered a relative
      contraindication to limb salvage surgery with an amputation seeming the preferred
      option. We present a review of 50 patients over the age of 80 years, presenting
      with ischaemic rest pain, ulceration or gangrene of the lower extremity. Six
      patients were treated conservatively, four of whom died during the same
      admission. Only two patients proved suitable for transluminal angioplasty as the
      sole curative procedure. Twelve patients (24%) underwent primary amputation with
      a perioperative mortality of 3/12 (25%). Five patients (10%) had an iliac bypass
      procedure, and 25 patients (50%) were considered suitable for infrainguinal
      bypass. Of the latter group 14 had femoropopliteal bypasses, and 11 had
      femorodistal bypasses with an overall perioperative mortality of 3/25 (12%).
      Mortality at 6 months was high (33%) and was similar in both the grafted and
      amputation groups. Patients having reconstruction fared well in terms of
      independent mobility, use of long-term care, and length of hospital stay.
      Patients over 80 years of age with critical ischaemia should not be denied the
      opportunity of vascular reconstruction.

PMID- 8285552
TI  - Incisional hernia after laparoscopic cholecystectomy.

PMID- 8285553
TI  - Laparoscopic vagotomy.

PMID- 8285554
TI  - Comparative vascular audit using the POSSUM scoring system.

PMID- 8285555
TI  - How long do patients convalescence after inguinal herniorrhaphy? Current
      principles and practice.

PMID- 8285556
TI  - An improved method for oesophageal intubation.

PMID- 8285557
TI  - Benign thyroid disease and vocal cord palsy.

PMID- 8285558
TI  - Gunshot wounds of the colon: ballistic considerations.

PMID- 8285559
TI  - Provision and acceptability of day case breast biopsy: an audit of current
      practice.

PMID- 8285560
TI  - Provision and acceptability of day case breast biopsy: an audit of current
      practice.

PMID- 8285561
TI  - [Doppler echocardiography under dipyridamole after thrombolyzed early myocardial
      infarction. Comparison with coronarographic data].
AB  - The reliability and safety of Doppler echocardiography with dipyridamole (0.84
      mg/kg in 10 min) were evaluated in 63 patients an average of 7 days after a
      thrombolysed early lateral infarct and 24 hours before follow-up coronary
      arteriography. The aims of the test were the detection of tight stenoses
      (diameter reduced by more than 75%) affecting the artery responsible for the
      infarct as well as the other coronary vessels, using the vasodilator action of
      dipyridamole. The echocardiographic manifestation of induced coronary steal
      consisted of transitory asynergism in the territory of the artery involved.
      Clinical tolerability of the test was good. The brief onset of anginal pain was
      nevertheless seen in 6 patients. Analysis of the zone corresponding to the
      necrosed area was possible in only 43 cases. Sensitivity of the test for
      detection of a post-infarction residual stenosis was 64% (39-89) and specificity
      90% (79-100). Study of other territories was possible in 59 cases. Sensitivity of
      the test for the diagnosis of multiple vessel disease was 70% (42-98) and
      specificity 94% (88-100). In the population as a whole, Doppler study of
      variations in anterograde mitral flow revealed a sensitivity of 40% (27-53) and
      specificity of 87% (78-96). Variations in sub-aortic flow were analysed only in
      the final 27 patients, with a sensitivity and specificity of 100%. The
      specificity of dipyridamole echocardiography after infarction is good, both for
      the detection of residual stenosis and that of multiple vessel disease, the chief
      limiting factor being the impossibility of analysis of the infarcted region in
      the presence of initial akinesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285562
TI  - [Surveillance of iatrogenic complications in a department of cardiology. Thoughts
      about a preventive strategy].
AB  - A study was made of iatrogenic complications (IC) occurring in the department of
      cardiology of the Nantes Teaching Hospital Group between May 31, 1990 and June 1,
      1991. One hundred and fifty eight IC were seen during this period, i.e. an annual
      incidence of 4.4%. There were 4 deaths following and IC, i.e. an annual mortality
      rate of 0.11%. Five other IC had serious though non-fatal consequences. Taken in
      general, IC appeared to be benign and of various origins. Drugs were responsible
      for almost half of IC and invasive investigations for one third. Application of a
      simple and single preventive approach is difficult in view of the diversity of
      causes. The solution lies in part in awareness and education concerning the
      problem, in which a permanent register system like ours certainly has a role to
      play.

PMID- 8285563
TI  - [A rare course of spastic angina with normal coronary arteries].
AB  - The authors report the case of a 65-year-old woman smoker monitored for spastic
      angina. A first coronary arteriogram in 1986 failed to reveal any significant
      coronary lesion and was complicated by reversible occlusive spasm of the anterior
      interventricular artery. A second coronary arteriogram 6 years later because of
      recurrence of angina revealed the development of 70% stenosis of the coronary
      segment affected by the spasm. Such an outcome is rarely reported in the
      literature and raise the question of a possible link between spasm and the
      progression of atheroma.

PMID- 8285564
TI  - [Thrombocytopenia caused by digitoxin overdose].
AB  - The authors report a new case of digitoxin-related thrombocytopenia. It involved
      a patient hospitalised for torsades de pointe in whom blood digitoxin was 85
      micromols/l on admission. This rare complication progressed to a satisfactory
      conclusion in seven days. The mechanism is immuno-allergic and/or toxic since
      thrombocytopenia occurs only following therapeutic overdose. The prognosis is
      determined by the cardiac arrhythmia rather than the hemostasis abnormality.
      Treatment is symptomatic and should include the withdrawal of digitoxin which can
      be replaced by digoxin. Oral activated charcoal decreases the plasma half-life by
      blocking the enterohepatic cycle and is hence recommended in this situation.

PMID- 8285565
TI  - [Ambulatory arterial blood pressure monitoring in the management of hypertension
      in pregnancy].
AB  - Ambulatory blood pressure monitoring (ABPM) completes the diagnostic approach to
      hypertension of pregnancy, by providing a dynamic study of the blood pressure
      status of the pregnant woman. It corrects certain erroneous diagnoses of
      hypertension of pregnancy, in particular those related to the "White coat"
      effect, especially common in pregnant women. ABPM enables the study of nocturnal
      blood pressured figures, known for their prognostic value in hypertension of
      pregnancy. Finally, while loss or reversal of circadian rhythm appears to be of
      good predictive value regarding the onset of eclampsia, it is above all blood
      pressure load which appears to be harmful to fetal growth and maturity. ABPM also
      facilitates management by improving the compliance of pregnant women with regular
      monitoring and with treatment, by more accurately guiding the surveillance of
      drug treatment.

PMID- 8285566
TI  - [Antithrombotic agents].

PMID- 8285567
TI  - Prevention of recurrent rectal carcinoma.

PMID- 8285568
TI  - Rectal carcinoma, type of surgery and the role of adjuvant radiation therapy.

PMID- 8285569
TI  - Experience with restorative proctocolectomy in 201 patients.
AB  - Two hundred and one patients underwent restorative proctocolectomy between
      January 1985 and January 1993. The underlying disease was ulcerative colitis in
      191 and familial adenomatous polyposis in ten patients. All patients had a J
      pouch and, except for 22 patients, total mucosectomy was performed. The procedure
      was technically successful in 200 cases (99.5%). There was no postoperative
      mortality, but two patients died soon afterwards due to unrelated causes
      (suicide, upper gastrointestinal bleeding). Early postoperative complications
      were observed in 33% of patients and 21% required reoperations, most often
      because of haemorrhage or pelvic sepsis. Late morbidity rate was 29% including
      reoperations in 31 patients (17%) and conversion to permanent ileostomy in five
      cases (2.5%). The most common late problems were anal sinus, stricture or fistula
      (11%) and episodic or chronic pouchitis (20%). The functional result was
      evaluated in 150 patients followed up for one year. the mean bowel frequency was
      5.6 times in 24 hours, 19% of patients had minor anal soiling and 11% required a
      protective pad. It is concluded that restorative proctocolectomy has become the
      first choice for most patients with ulcerative colitis and familial adenomatous
      polyposis.

PMID- 8285570
TI  - Peptic ulcer surgery in the nineties: patient profile, immediate results and
      clinical findings.
AB  - The decreasing frequency of elective ulcer surgery and the persisting frequency
      of emergency surgery for peptic ulcer diseases has often been reported. The
      reason for the divergent epidemiological behaviour of the two subgroups of
      surgical candidates is not clear. The present cross-sectional, population-based
      analysis of patients undergoing peptic ulcer surgery evaluates the mode of
      preoperative therapy in elective and emergency cases. It also assesses the
      present frequency of peptic ulcer surgery, ulcer complications, and the immediate
      results of ulcer surgery in a target population. The evaluation concerned 117
      adult patients (F/M ratio 1/1.1, mean age 58.7 +/- 1.8 years) operated on for
      peptic ulcer disease in Helsinki City between March 1990 and February 1991. The
      annual frequency of elective surgery was 8.3 and of emergency surgery 20.7 per
      10(5) residents in Helsinki. 30% of the patients treated surgically had no
      preoperative symptoms or antiulcer medication; the others were on on-demand type
      H2-receptor antagonist therapy. Whereas there was no mortality from the elective
      surgery the mortality rate for the emergency surgery was 10%, mainly due to
      cardiopulmonary reasons among elderly, high-risk patients. In conclusion, since
      our previous report for 1987 for the same target population in Helsinki, the
      incidence of emergency surgery has additionally increased, while the incidence of
      elective surgery has continuously decreased.

PMID- 8285571
TI  - Preoperative ultrasound in patients undergoing initial neck exploration for
      primary hyperparathyroidism.
AB  - 92 patients with primary hyperparathyroidism were subjected prospectively to
      preoperative ultrasound to identify enlarged parathyroid glands and detect
      simultaneous thyroid lesions of surgical significance. The overall sensitivity
      and specificity rates were 62.7% and 95.7%, 85.2% and 96.8% for patients with a
      single adenoma, 44.3% and 88% for those with multiglandular disease, 56.8% and
      95.6% for those with simultaneous thyroid disease and 20% and 100% for
      mediastinal glands. Ultrasound revealed a pathological thyroid gland in 26
      patients (28%). The sensitivity and specificity rates were 96% and 100%. The
      thyroid lesion was considered clinically significant in 15 of the 92 patients
      (16.3%) and only in three patients (3.3%) was the diagnosis not established
      preoperatively. Operating room times and costs were significantly lower for
      patients with an accurate ultrasound scan than for those with an inaccurate scan
      (P < 0.001). We conclude that both the sensitivity of ultrasound for locating
      enlarged parathyroid glands and its yield of previously unknown thyroid lesions
      of surgical significance are too low to warrant preoperative ultrasound
      evaluation. Although our operating room expenses were significantly higher for
      patients with an inaccurate scan, the cost effectiveness of preoperative
      ultrasound cannot be proved until a prospective, randomised investigation has
      been carried out.

PMID- 8285572
TI  - Indications for surgery in penetrating chest injuries.
AB  - This study is concerned with the outcome of treatment of 933 patients with
      penetrating gunshot chest injuries at the Medical Academy in Afghanistan. The
      most important factors to determine the choice of management were the general
      state of the patient, the type and location of the injury and the arrival time.
      326 (34.9%) patients needed thoracic resuscitation. There were 117 (12.6%) cases
      of thoracotomy (91 emergency, 26 early operations). Of the conservative treatment
      group there were 636 (68.2%) cases of thoracostomy, 105 (11.2%) of repeated
      thoracocentesis, and as few as 75 (8.0%) required medical treatment only. There
      were 106 cases of the late thoracotomy because of empyema in 97 patients,
      fibrothorax and foreign body in eight cases and lung cystoma in one patient. The
      overall mortality rate was 9.4% with 5.5% in the group of isolated injuries and
      26.7% in the group of combined injuries. The long-term results show that 488
      (86.5%) of 564 patients were well enough to return to work and 39 (6.9%) were
      still suffering from secondary pulmonary disease.

PMID- 8285573
TI  - Lower-limb amputations.
AB  - The current epidemiological situation with regard to lower-limb amputations in
      southern Finland was analysed for the year 1989. Lower-limb amputations were
      performed on 268 patients. The amputation rate was 22.0 per 100,000 inhabitants,
      and the mean age of amputees was 70 years. Peripheral vascular disease was the
      main reason for amputation (79%). The most common level of amputation was above
      knee (49%) followed by below-knee (29%). Two thirds (64%) of the patients lived
      over one year, and half (53%) over two years after the amputation. In the group
      of patients undergoing unilateral amputation and surviving over two months, 26%
      of the above-knee and 63% of the below-knee amputation patients received a
      prosthesis. The (average) time lag between surgery and fitting the prosthesis was
      97 days. Incidence and mortality were decreased after 1985. The rate of
      prosthesis fitting was still low but the time lag between surgery and prosthetic
      fitting had decreased.

PMID- 8285574
TI  - A histomorphometric study of rabbit tibiofibular bones after rigid intramedullary
      nailing.
AB  - The effects of rigid intramedullary nailing on cortical bone structure were
      studied in osteotomized and non-osteotomized rabbit tibiofibular bone at time
      intervals ranging from three to 24 weeks postoperatively. Histological specimens
      were analysed morphometrically observing changes in cortical bone and the
      medullary cavity in transverse sections distal to the tibiofibular junction.
      Throughout the series, when compared to intact control bones, computerized
      planimetry revealed significant differences only in the osteotomized bones. At 24
      weeks, the area of whole cortical bone was less and the area of the medullary
      cavity greater in the osteotomized bones than in respective control bones. The
      reason for these changes seemed to be a profound resorption of subendosteal bone.
      The amount of cortical osteoporosis was slight, but a steady increase could be
      seen towards the end of the experiment. The results suggest that the
      morphological changes in cortical bone detected in the present study mostly
      depend on the operative trauma and not so much on the protection from stress
      provided by the rigid intramedullary nail.

PMID- 8285575
TI  - Holding power of metallic plates in cancellous bone. An experimental study on
      rabbits with polymethyl methacrylate as supporting material.
AB  - The holding power of a metallic device in cancellous bone was tested in sixteen
      rabbits (n = 16). The device was fixed with the support of polymethyl
      methacrylate. The fixation firmness was studied radiologically and by measuring
      the bonding strength. The mean value of the bonding strength was 485 N (n = 6) at
      6 weeks, and 557 N (n = 8) at 12 weeks.

PMID- 8285576
TI  - Thoracoscopic fundoplication.
AB  - Thoracoscopic fundoplication and hiatoplasty were performed by a videoassisted
      technique in a patient with longstanding pathologic gastro-oesophageal reflux,
      reflux oesophagitis and hiatal hernia. Ten months later the patient was
      asymptomatic and had normal findings by oesophageal endoscopy and 24-hour pH
      monitoring. Thoracoscopic fundoplication may be useful in patients with intra
      abdominal adhesions due to previous abdominal surgery. Also obese patients with
      large hiatal hernias and perioesophageal adhesions may benefit from the
      thoracoscopic approach.

PMID- 8285577
TI  - Aneurysm of the iliac artery in Marfan's syndrome.
AB  - There appears to be an association between iliac artery aneurysm and Marfan's
      syndrome. A case of iliac artery aneurysm in a young male with the disorder is
      presented. The iliac aneurysm was successfully managed by arterial reconstruction
      with a prosthesis. Patients with Marfan's syndrome should be followed for signs
      of weakness of the peripheral arterial system.

PMID- 8285578
TI  - Pancreatic lymphoma.
AB  - Primary lymphoma of the pancreas is an extremely rare condition. There are no
      previous reports from northern Europe. It is important to differentiate
      pancreatic carcinoma from lymphoma because there is significant difference
      between the prognosis and treatment. We describe here a case of primary
      pancreatic lymphoma in a 64-year-old woman who was admitted to hospital because
      of a sudden abdominal pain and vomiting. Ultrasound, computed tomography and
      endoscopic retrograde cholangiopancreatography findings are presented, and the
      features of pancreatic lymphoma in these imaging studies are discussed.

PMID- 8285579
TI  - Myotonic dystrophy patients have larger CTG expansions in skeletal muscle than in
      leukocytes.
AB  - The genetic basis of myotonic dystrophy is an unstable expansion of CTG repeats
      located in a gene on chromosome 19 that encodes a putative serine/threonine
      protein kinase. We studied the somatic mosaicism of the (CTG)n expansion in
      myotonic dystrophy patients. (CTG)n expansions were 2- to 13-fold greater in DNA
      isolated from skeletal muscle than in DNA from leukocytes in 10 of 11 patients
      with myotonic dystrophy. Different muscles of the same individual showed similar
      (CTG)n expansions. In postmortem tissues from an adult patient, (CTG)n expansions
      in brain, skeletal muscle, cardiac muscle, testes, and liver were all greater
      than in leukocytes. Normal myotonic dystrophy gene alleles from 7 healthy
      subjects had the same number of CTG repeats in leukocytes and muscle. The
      myotonic dystrophy mutation displays pronounced heterogeneity in somatic cells.
      The (CTG)n expansion observed in peripheral blood leukocytes is not necessarily
      representative of the repeat expansion in affected tissues, such as skeletal
      muscle and myocardium. In some patients with myotonic dystrophy, the predictive
      value of genetic analysis based on leukocyte DNA may be limited.

PMID- 8285580
TI  - Influence of visual information on cerebellar saccadic dysmetria.
AB  - We compared the accuracy of saccades made to seen or remembered visual targets in
      3 patients with saccadic dysmetria due to cerebellar lesions. Saccadic dysmetria
      was worse for saccades to remembered targets and for saccades to flashed targets
      visible for only 150 msec (i.e., invisible at the time of saccade). Furthermore,
      no corrective saccades were made if the target was not visible. These results
      have implications for testing saccadic dysmetria and suggest new hypotheses about
      the control of saccadic amplitude.

PMID- 8285581
TI  - Herpes simplex type 2 in a patient with Mollaret's meningitis: demonstration by
      polymerase chain reaction.
AB  - We describe a patient with recurrent self-limited aseptic meningitis meeting the
      criteria for Mollaret's syndrome, in whom extensive serological investigation and
      cerebrospinal fluid analysis failed to reveal a specific cause. Using polymerase
      chain reaction techniques to amplify herpes simplex viral DNA, we were able to
      identify the presence of herpes simplex virus type 2 in the cerebrospinal fluid.
      The duration of clinical illness may have been shortened by treatment with
      intravenous acyclovir. We suggest that herpes simplex virus may be a more common
      cause of aseptic meningitis than has been demonstrated by current commonly
      available serological and culture techniques.

PMID- 8285582
TI  - Human beta-mannosidase deficiency associated with peripheral neuropathy.
AB  - Human beta-mannosidosis is an inherited lysosomal storage disorder described in
      only seven families. We present a further case in a black African 14-year-old boy
      with severely deficient beta-mannosidase activity, bilateral thenar and
      hypothenar amyotrophy, electrophysiologically demonstrable demyelinating
      peripheral neuropathy, and cytoplasmic vacuolation of skin fibroblasts and
      lymphoid cells. The clinical and biochemical features of our patient are compared
      to those of previously reported patients.

PMID- 8285583
TI  - Absence of hereditary mutations in exons 5 through 9 of the p53 gene and exon 24
      of the neurofibromin gene in families with glioma.
AB  - Inherited mutations of the p53 and neurofibromin genes are thought to cause two
      distinct neoplastic disorders in which gliomas occur, the Li-Fraumeni syndrome
      and neurofibromatosis type 1. We investigated the possibility that inherited
      mutations in specific regions of these genes also contributed to the clustering
      of gliomas in otherwise normal families. Twenty-six members of 16 families with
      glioma were screened for germline mutations of exons 5 through 9 of the p53 gene
      and exon 24 of the neurofibromin gene using a polymerase chain reaction-single
      strand conformation polymorphism method. No germline mutations were found,
      suggesting that the genetic basis of familial glioma is distinct from that of
      gliomas occurring in the Li-Fraumeni syndrome, and that inherited mutations of
      the catalytic domain of neurofibromin do not predispose affected glioma families
      to these tumors.

PMID- 8285584
TI  - Congenital Horner's syndrome does not alter Lisch nodule formation.
AB  - A 21-year-old woman with neurofibromatosis type 1 (NF-1) had a unilateral
      congenital Horner's syndrome with resultant hypopigmentation of the affected
      iris. Lisch nodules, which are melanocytic hamartomas, were similar in number,
      size, and pigmentation in both eyes. The present findings suggest that the
      formation of Lisch nodules is not influenced by the presence or absence of
      sympathetic innervation of the iris.

PMID- 8285585
TI  - Human immunodeficiency virus infection of the nervous system.

PMID- 8285586
TI  - Recurrent stroke caused by spondylotic compression of the vertebral artery.

PMID- 8285587
TI  - Concentric sclerosis (Balo): morphometric and in situ hybridization study of
      lesions in six patients.
AB  - Brain tissues from 6 patients with concentric sclerosis (Balo) were examined by
      in situ hybridization, immunocytochemistry, morphometry, and histological
      methods. The patients were 24 to 48 years old and had progressive cerebral
      symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most
      frequent in the frontal white matter, contained alternating bands of demyelinated
      and partly myelinated white matter that were arranged in concentric or mosaic
      patterns. In the areas of demyelination, axons were relatively well preserved and
      there were perivascular inflammatory infiltrates. In 2 specimens, lesions
      contained regions with the characteristic appearance of actively demyelinating
      multiple sclerosis plaques. Oligodendroglial densities were highest in normal
      appearing white matter, lower in partially myelinated areas, and lowest in
      demyelinated areas, which also contained many hypertrophic astrocytes closely
      associated with oligodendroglia. Messenger RNA levels for myelin-related proteins
      followed the same pattern; they were lowest in demyelinated areas, higher in
      partially myelinated areas, and highest in normal-appearing white matter beyond
      lesion margins. Our findings suggest that concentric sclerosis is a variant of
      multiple sclerosis, that oligodendroglial loss is important in the pathogenesis
      of demyelination, and that partially myelinated areas probably represent stages
      of ongoing myelin breakdown rather than remyelination of previously demyelinated
      areas.

PMID- 8285588
TI  - Cerebellar control of movement.

PMID- 8285589
TI  - Localization of non-N-methyl-D-aspartate glutamate receptors in normal and
      Alzheimer hippocampal formation.
AB  - The hippocampi and adjacent temporal cortices of 24 human brains were examined
      with antibodies to the GluR1, GluR2/3, and GluR4 subunits of the D,L-alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid-preferring glutamate receptor. GluR1
      immunoreactivity was most dense in the dentate gyrus, with lower densities in
      other hippocampal and cortical regions. GluR2/3 immunoreactivity was the most
      intense of the three antibodies, with high levels throughout most hippocampal
      subfields, where it was localized to cell bodies, proximal axons, and dendrites.
      GluR4 immunoreactivity was very sparse in all regions. In Alzheimer's disease
      brains, the general pattern of staining was similar to that seen in control
      brains. GluR1 and GluR4 immunoreactivity was seen in some but not all neuritic
      plaques. All three antibodies recognized some neurons undergoing neurofibrillary
      degeneration.

PMID- 8285590
TI  - Indices of oxidative stress and mitochondrial function in individuals with
      incidental Lewy body disease.
AB  - Brain tissue from normal individuals with incidental Lewy bodies and cell loss in
      pigmented substantia nigra neurons (asymptomatic Parkinson's disease) and age
      matched control subjects without nigral Lewy bodies was examined biochemically.
      There was no difference in dopamine levels or dopamine turnover in the caudate
      and putamen of individuals with incidental Lewy body disease compared to control
      subjects. There were no differences in levels of iron, copper, manganese, or zinc
      in the substantia nigra or other brain regions from the individuals with
      incidental Lewy body disease compared to those from control subjects. Similarly,
      ferritin levels in the substantia nigra and other brain areas were unaltered.
      There was no difference in the activity of succinate cytochrome c reductase
      (complexes II and III) or cytochrome oxidase (complex IV) between incidental Lewy
      body subjects and control subjects. Rotenone-sensitive NADH coenzyme Q1 reductase
      activity (complex I) was reduced to levels intermediate between those in control
      subjects and those in patients with overt Parkinson's disease, but this change
      did not reach statistical significance. The levels of reduced glutathione in
      substantia nigra were reduced by 35% in patients with incidental Lewy body
      disease compared to control subjects. Reduced glutathione levels in other brain
      regions were unaffected and there were no changes in oxidized glutathione levels
      in any brain region. Altered iron metabolism is not detectable in the early
      stages of nigral dopamine cell degeneration. There may be some impairment of
      mitochondrial complex I activity in the substantia nigra in Parkinson's
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285591
TI  - Cerebellar hypermetria is larger when the inertial load is artificially
      increased.
AB  - Hypermetria is a classical cerebellar symptom designating the overshoot observed
      when a patient is asked to make a very fast and accurate movement. The movement
      studied here was wrist flexion. Hypermetria was found to be increased by
      artificially increasing the inertia of the moving hand. A normal subject adapted
      himself to increasing inertia by increasing both his agonist activity (the
      launching force) and its antagonist activity (the braking force). In the same
      circumstances, a patient with symptoms of cerebellar system dysfunction was found
      to be able to increase his agonist activity but not his antagonist activity.

PMID- 8285592
TI  - Carotid endarterectomy: trials and tribulations.
AB  - Since its introduction 40 years ago, the value of carotid endarterectomy has been
      controversial. In the early 1980s, several clinical trials were initiated to
      determine the efficacy of this operation in patients with carotid stenoses who
      were either symptomatic or asymptomatic for retinal or hemispheric ischemia. In
      1991, interim results were published for the North American Symptomatic Carotid
      Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST), both
      reporting efficacy for surgery in patients with symptomatic carotid artery
      stenosis of greater than 70%. Subgroup analyses revealed variable risk groups.
      The Veterans Administration (VA) Symptomatic Trial (Cooperative Studies Program
      309 of the Department of Veterans Affairs) terminated early because of these
      results and its findings were consistent with the results of the larger trials.
      NASCET and ECST continue for symptomatic patients with carotid stenoses between
      30% and 69%. The results of three trials in asymptomatic patients, the Mayo
      asymptomatic trial, the Carotid Artery Stenosis with Asymptomatic Narrowing:
      Operation Versus Aspirin trial, and the VA Asymptomatic Trial (Cooperative
      Studies Protocol 167 of the Department of Veterans Affairs), have been reported.
      None showed a statistically significant benefit for surgery in the prevention of
      stroke or death. However, none was sufficiently large to exclude such a benefit.
      The large Asymptomatic Carotid Atherosclerosis Study is in progress. Differences
      in the results and design of these trials are discussed as are restrictions in
      the applicability of their results.

PMID- 8285593
TI  - Acute lumbosacral polyradiculopathy in acquired immunodeficiency syndrome:
      experience in 23 patients.
AB  - We reviewed our experience in 23 patients with acquired immunodeficiency syndrome
      (AIDS) who had acute lumbosacral polyradiculopathy. The patients developed a
      distinctive syndrome of rapidly progressive flaccid paraparesis and areflexia
      that was frequently associated with sphincter disturbances. Persuasive laboratory
      evidence of a cytomegalovirus polyradiculopathy (polymorphonuclear pleocytosis or
      confirmatory cerebrospinal fluid culture) was found in 15 of the 23 patients.
      Treatment with ganciclovir in these patients led to clinical stabilization,
      although worsening during the first 2 weeks of treatment was common. Most
      patients with cytomegalovirus polyradiculopathy had severe residual deficits.
      Metastasis from systemic lymphoma accounted for the polyradiculopathy in 2 other
      patients. A more benign syndrome was identified in the remaining 6 patients. They
      generally had slower clinical progression and less severe neurological deficits
      at their nadir than did patients with cytomegalovirus polyradiculopathy. Unlike
      patients with cytomegalovirus infection, their cerebrospinal fluid showed a
      predominantly mononuclear pleocytosis. Moreover, spontaneous improvement without
      treatment was common. Our experience together with the published experience of
      others suggests that the acute lumbosacral polyradiculopathy in AIDS is a
      clinical syndrome with different etiologies and variable clinical outcome.
      Recognition of this heterogeneity is necessary for the management of individual
      patients, as well as the interpretation of treatment results.

PMID- 8285594
TI  - Autosomal dominant Lewy body parkinsonism in a four-generation family.
AB  - We report a family with autosomal dominant parkinsonism. The propositus developed
      parkinsonism at a relatively young age (45 years) and came to autopsy after a 6
      year illness. She had typical features of Parkinson's disease except for an
      absence of rest tremor, although this was present in other family members. A
      diagnosis of Lewy body parkinsonism was confirmed by neuropathological
      examination. Additional pathological features included the presence of cortical
      Lewy bodies and anti-ubiquitin-positive neurites in the cornu Ammonis 2 and 3
      (CA2-3) region of the hippocampus. This kindred is similar both clinically and
      pathologically to a few previously reported pedigrees, further strengthening
      recent evidence of a genetic etiology of some forms of Parkinson's disease.

PMID- 8285595
TI  - Oligodendrocytes in the early course of multiple sclerosis.
AB  - The neuropathology of demyelinating lesions in multiple sclerosis was studied in
      specimens obtained by diagnostic needle biopsy during early stages of the
      disease. The lesions were characterized by a chronic inflammatory reaction
      dominated by lymphocytes and macrophages, plaque-like demyelination, and
      astroglial sclerosis. Oligodendrocytes within the lesions were studied by
      immunocytochemistry using antibodies against various myelin and oligodendroglia
      components. The expression of messenger RNA for proteolipid protein was
      determined by in situ hybridization. Our studies revealed that myelin
      oligodendrocyte glycoprotein is a sensitive and reliable marker for
      identification of oligodendrocytes in demyelinated plaques. The results suggest
      that in the early course of the disease in some patients, oligodendrocytes may
      largely be preserved, whereas in others oligodendroglial loss is pronounced. Loss
      of oligodendrocytes was only marginally related to the stage of demyelinating
      activity within the lesions. These findings indicate that the pathogenesis of
      demyelination may vary within different multiple sclerosis patients.

PMID- 8285596
TI  - Synaptotagmin can cause an immune-mediated model of Lambert-Eaton myasthenic
      syndrome in rats.
AB  - The possible antigenicity of synaptotagmin, a synaptic vesicle protein acting as
      a cooperative calcium (Ca2+) receptor in exocytosis, was tested to determine
      whether it is involved in the induction of Lambert-Eaton myasthenic syndrome in
      which antibodies against voltage-dependent Ca2+ channels or related molecules
      play a pathogenic role. Repeated injections to Lewis rats with peptides of
      synaptotagmin residues 20 through 53 or 1 through 30 that are presumably exposed
      at the nerve terminal surface during exocytosis induced corresponding antipeptide
      antibodies; on immunoblots, antibodies recognized synaptotagmin that was
      expressed in the clonal cells. Electrophysiologically, the peptide (residues 20
      53)-immunized rats showed (1) reduced acetylcholine quantal content of end-plate
      potential, (2) an increase in quantal content at high extracellular Ca2+
      concentration, and (3) early facilitation followed by less marked depression of
      end-plate potential amplitude at a tetanic rate of repetitive nerve stimulation.
      Findings are similar to those in human Lambert-Eaton myasthenic syndrome and
      passively transferred Lambert-Eaton myasthenic syndrome in mice, and thus suggest
      that antibody to a synaptotagmin-voltage-dependent Ca2+ channel complex may be
      involved in the pathogenesis of Lambert-Eaton myasthenic syndrome. The peptide
      (residues 1-30)-immunized rats showed no electrophysiological abnormality.

PMID- 8285597
TI  - Alzheimer's disease and Lewy body disease: a comparative clinicopathological
      study.
AB  - The exact nature of the relationship between Lewy body disease and Alzheimer's
      disease (AD) is unknown. To investigate this, we compared cases of pure Lewy body
      disease, mixed Lewy body disease with AD, and pure AD to see what pathological
      features were shared and how they differed. We counted neurons, Lewy bodies,
      diffuse and neuritic senile plaques, neurofibrillary tangles, and neuropil
      threads in the frontal and medial temporal cortex and hippocampus from 5
      autopsied cases of Lewy body disease (without AD histopathology), 7 with combined
      Lewy body disease and AD, 6 with AD, and 5 age-matched normal control subjects.
      Average neuronal counts in the cases with Lewy body disease were
      indistinguishable from those of control subjects, but higher than those for AD
      and combined Lewy body disease and AD. Diffuse plaque densities were similar in
      all disease forms. Neuritic senile plaques, neurofibrillary tangles, and neuropil
      threads were numerous in AD and combined Lewy body disease and AD, but sparse or
      absent in Lewy body disease and controls. Pure Lewy body disease and AD appear to
      be distinct clinicopathological entities except for the common feature of diffuse
      plaques in both disorders.

PMID- 8285598
TI  - [Brain evolution of the human from the paleoneurologic viewpoint].
AB  - Paleoneurology interprets natural or artificial endocasts. It is, therefore, the
      only method which is able to provide direct information on the ancestry of the
      human brain. Australopithecus, Homo habilis and Homo erectus are of outstanding
      importance concerning human evolution. This short review deals with some well
      preserved endocasts of these forms. Possibilities and limitations of
      paleoneurology are discussed with respect to the taxonomic attribution of fossil
      specimens. Functional aspects of the cortical sulcus pattern can be interpreted
      rather strictly and is, therefore, of considerably phylogenetic significance. It
      indicates that even some early hominids exhibit a human-like brain organization
      (e.g. KNM-ER 1470) while others (such a KNM-ER 1805) feature a rather pongid-like
      brain organization. However, controversy over the interpretation of endocasts
      from early hominids continues: It has not been possible to unequivocally
      demonstrate a human-like feature of the Australopithecus brain.

PMID- 8285599
TI  - Life style, subsistence and mortality in the Slavonic village at Espenfeld (Kr.
      Arnstadt, FRG). A trace element study.
AB  - Since the burial site of the Slavonic settlement at Espenfeld, Germany (10th to
      12th century AD), has been completely excavated, the skeletons are representative
      of the historic population. This skeletal series has also been intensively
      investigated both archaeologically and anthropologically. It thus belongs to the
      kind of museum specimens which should not be left apart from any further study
      made possible by technological improvements. Analysis of elements Ca, P, Sr, Ba,
      Zn, Pb and As from compact bone specimens of a subsample of this series was
      carried out to get a more detailed knowledge on the population's life style.
      After a consideration of site-specific diagenesis, reconstruction of subsistence
      was possible for both adults and children. The assessment of weaning practice
      revealed insights into childcare. Special consideration was given to hazardous
      elements and their influence on infant morbidity. Also, a presumed genetic
      relationship between certain individuals based on morphological traits was
      paralleled by a striking similarity of trace element profiles, suggesting that
      bone chemistry might also permit the differentiation of microenvironments.

PMID- 8285600
TI  - Dental agenesis in Sardinians.
AB  - The authors report on the results of a study on the dental agenesis frequency in
      a sample of 420 individuals (152 males, 268 females), aged between 8 and 20
      years, from Sardinia (Italy). 18.33% of the examined individuals (22 males, 55
      females) show congenital absence and/or morphometric reduction of at least one
      tooth. The frequency of congenital absence of teeth in Sardinians lies in the
      middle of the range of Caucasoid populations, but the average (mean = 1.7) per
      individual seems to be the lowest ever reported. In some traits of agenesis
      Sardinians show great similarity to other isolated populations. This suggests
      that dental agenesis is probably affected by the same factors (e.g. isolation and
      inbreeding), which are responsible for the present genetic structure of the
      Sardinian population.

PMID- 8285601
TI  - Changes in birth weight, birth length and head circumference of Hungarian
      children in the county Baranya between 1968 and 1979-1981.
AB  - Possible secular changes of newborn's body measurements were investigated in a
      cross-sectional growth study in the County Baranya (South Hungary) in 1979-1981.
      The total sample includes 2,130 children. The results were compared with those
      obtained by Fekete et al. (1968, 1974) in the same region on 3,567 neonates.
      During the 12-years interval the birth weight increased slightly. The head
      circumference did not change in girls, but decreased slightly in boys. The birth
      length values could not be evaluated because of technical reasons. According to
      the present results secular changes in the body measurements of the newborns
      could not be seen during the investigated period. The fetal growth standard
      values ascertained by Fekete et al. (1968, 1974) are still suitable. A repeated
      anthropometric investigation of newborns is necessary in the near future.

PMID- 8285602
TI  - Stature and footsize in four Thai communities of Assam, India.
AB  - An attempt has been made to examine correlationships between stature and
      footlength, stature and footbreadth, and footlength and breadth among four Thai
      (male) populations of Assam (India), viz. the Khamyangs, the Turungs, the Aitons
      and the Khamitis. Significant positive correlations have been found in all the
      cases. Mean values of the indices have revealed a more or less constant ratio of
      stature and footsize at all heights suggesting the possibility of estimating
      stature from footlength or breadth and vice versa. Estimation of stature from
      footlength is, however, preferable to estimation from footbreadth. The Turungs
      stand for the tallest in stature and biggest foot measurements. They fall into
      'medium' stature of the Martin's scale while the others fall into 'below medium'.
      Statistically significant difference has been observed the Turungs and the
      Khamyangs in respect of footbreadth, between the Turungs and the Aitons in
      footlength and, between the Khamyangs and the Khamtis in respect of stature
      footbreadth index.

PMID- 8285603
TI  - Antibiotic-supersusceptible mutants of Escherichia coli and Salmonella
      typhimurium.

PMID- 8285604
TI  - Azithromycin inhibition of intracellular Legionella micdadei.
AB  - Legionella micdadei is an intracellular parasite that is ingested, but not
      killed, by leukocytes. Within monocytes, the organism has been shown to grow 1.0
      to 2.0 log10 units over 48 h (D. L. Weinbaum, R. R. Benner, J. N. Dowling, A.
      Alpern, A. W. Pasculle, and G. R. Donowitz, Infect. Immun. 46:68-73, 1984).
      Intracellular L. micdadei would appear to be a useful model in which to study the
      effect of antibiotics which accumulate intracellularly. Azithromycin, a newly
      introduced azalide, is highly concentrated within leukocytes and was therefore
      studied to determine its effect on a single strain of L. micdadei that had been
      ingested by human monocytes. Peripheral blood monocytes were allowed to ingest L.
      micdadei and extracellular, nonadherent organisms were subsequently removed by
      washing. Cells and cell-associated bacteria were then incubated at 0, 24, and 48
      h in media with serial concentrations of azithromycin at sub-MIC levels (less
      than 1.0 microgram/ml). L. micdadei in cells not exposed to azithromycin grew 0.8
      +/- 0.1 log10 units (mean +/- standard deviation) at 24 h and 1.7 +/- 0.4 log10
      units at 48 h. At both 24 and 48 h, the lowest concentrations of azithromycin
      tested (0.02 microgram/ml) significantly inhibited bacterial growth in monocytes
      (P = 0.02). A stepwise inhibition of L. micdadei CFUs was noted with increasing
      azithromycin concentrations. In contrast, when cells were exposed to antibiotic
      before ingesting L. micdadei, a less effective antibacterial effect was noted.
      Under certain in vitro conditions, azithromycin is a potent agent against
      intracellular L. micdadei.

PMID- 8285605
TI  - Treatment of acute experimental toxoplasmosis with investigational poloxamers.
AB  - Because of the limited chemotherapeutic approaches available to treat reactivated
      latent Toxoplasma gondii infection manifested as toxoplasmic encephalitis in AIDS
      patients, investigation of novel chemotherapeutic agents is warranted. Several
      poloxamers (nonionic block copolymers composed of a central hydrophobic chain of
      polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene) were
      tested for their abilities to alter the course of acute infection with a highly
      virulent T. gondii in mice. The effect varied markedly with the length of the
      constituent chains of the copolymers. The most effective preparations were highly
      effective when administered after infection and afforded remarkable protection
      against 10 to 1,000 100% lethal doses of T. gondii. Protection was dose
      dependent, and multiple treatments were more effective than single treatment.
      These preliminary findings warrant additional studies to determine whether this
      novel form of antitoxoplasma chemotherapy may prove promising in the treatment or
      prevention of acute toxoplasmic encephalitis in humans.

PMID- 8285606
TI  - In vitro and in vivo antibacterial activities of the glycylcyclines, a new class
      of semisynthetic tetracyclines.
AB  - N,N-Dimethylglycylamido (DMG) derivatives of minocycline and 6-demethyl-6
      deoxytetracycline are new semisynthetic tetracyclines referred to as the
      glycylcyclines. The in vitro activities of the glycylcyclines were evaluated in
      comparison with those of minocycline and tetracycline against strains carrying
      characterized tetracycline resistance determinants and against 995 recent
      clinical isolates obtained from geographically distinct medical centers in North
      America. The glycylcyclines were active against tetracycline-resistant strains
      carrying efflux [tet(A), tet(B), tet(C), and tet(D) in Escherichia coli and
      tet(K) in Staphylococcus aureus] and ribosomal protection [tet(M) in S. aureus,
      Enterococcus faecalis, and E. coli)] resistance determinants. Potent activity
      (MIC for 90% of strains, < or = 0.5 microgram/ml) was obtained with the
      glycylcyclines against methicillin-susceptible and methicillin-resistant S.
      aureus, E. faecalis, Enterococcus faecium, and various streptococcal species. The
      glycylcyclines exhibited good activity against a wide diversity of gram-negative
      aerobic and anaerobic bacteria, most of which were less susceptible to
      minocycline and tetracycline. The activities of the glycylcyclines against most
      organisms tested were comparable to each other. The in vivo efficacies of the
      glycylcyclines against acute lethal infections in mice when dosed intravenously
      were reflective of their in vitro activities. The glycylcyclines had efficacies
      comparable to that of minocycline against infections with methicillin-susceptible
      and methicillin-resistant S. aureus strains, a strain carrying tet(K), and a
      tetracycline-susceptible E. coli strain but exceeded the effectiveness of
      minocycline against infections with resistant isolates, including strains
      harboring tet(M) or tet(B). Levels of DMG-6-deoxytetracycline in serum were
      higher and more sustained than those of DMG-minocycline or minocycline. Our
      results show that the glycylcyclines have potent in vitro activities against a
      wide spectrum of gram-positive and gram-negative, aerobic and anaerobic bacteria,
      including many resistant strains. On the basis of their in vitro and in vivo
      activities, the glycylcyclines represent a significant advance to the
      tetracycline class of antibiotics and have good potential value for clinical
      efficacy.

PMID- 8285607
TI  - Pharmacokinetics, oral bioavailability, and metabolic disposition in rats of (-)
      cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine, a nucleoside
      analog active against human immunodeficiency virus and hepatitis B virus.
AB  - The pharmacokinetics and metabolism of the potent anti-human immunodeficiency
      virus and anti-hepatitis B virus compound, (-)-cis-5-fluoro-1-[2-(hydroxymethyl)
      1,3-oxathiolan-5-yl] cytosine (FTC), were investigated in male CD rats. Plasma
      clearance of 10 mg of FTC per kg of body weight was biexponential in rats, with a
      half-life at alpha phase of 4.7 +/- 1.1 min (mean +/- standard deviation) and a
      half-life at beta phase of 44 +/- 8.8 min (n = 5). The total body clearance of
      FTC was 1.8 +/- 0.1 liters/h/kg, and the oral bioavailability was 90% +/- 8%. The
      volume of distribution at steady state (Vss) was 1.5 +/- 0.1 liters/kg.
      Increasing the dose to 100 mg/kg slowed clearance to 1.5 +/- 0.2 liters/kg/h,
      lowered the Vss to 1.2 +/- 0.2 liters/kg, and reduced the oral bioavailability to
      65% +/- 15%. FTC in the brains of rats was initially less than 2% of the plasma
      concentration but increased to 6% by 2 h postdose. Probenecid elevated levels of
      FTC in plasma as well as in brains but did not alter the brain-to-plasma ratio.
      The urinary and fecal recoveries of unchanged FTC after a 10-mg/kg intravenous
      dose were 87% +/- 3% and 5% +/- 1.6%, respectively. After a 10-mg/kg oral dose,
      respective urinary and fecal recoveries were 70% +/- 2.5% and 25% +/- 1.6%. Two
      sulfoxides of FTC were observed in the urine, accounting for 0.4% +/- 0.03% and
      2.7% +/- 0.2% of the intravenous dose and 0.4% +/- 0.06% and 2.5% +/- 0.3% of the
      oral dose. Also observed were 5-fluorocytosine, representing 0.4% +/- 0.06% of
      the intravenous dose and 0.4% +/- 0.07% of the oral dose, and FTC glucuronide,
      representing 0.7% +/- 0.2% of the oral dose and 0.4% +/- 0.2% of the intravenous
      dose. Neither deaminated FTC nor 5-fluorouracil was observed in the urine (less
      than 0.2% of dose). The high oral availability and minimal metabolism of FTC
      encourage its further preclinical development.

PMID- 8285608
TI  - Liposome-incorporated ciprofloxacin in treatment of murine salmonellosis.
AB  - We used a dehydration-rehydration procedure in order to efficiently incorporate
      ciprofloxacin into phospholipid vesicles (liposomes), which we then used to treat
      BALB/c mice that had been infected per os with Salmonella dublin. A single
      injection of liposome-incorporated ciprofloxacin (LIC) was 10 times more
      effective than a single injection of free drug at preventing mortality. When free
      ciprofloxacin was administered twice daily for 5 days, it was more effective than
      when it was administered as a single dose. Treatment with LIC produced dose
      dependent decreases in bacterial counts in spleen, stool, and Peyer's patches,
      indicating that the drug had distributed to all areas of inflammation, not just
      to the major reticuloendothelial system organs. Although LIC was cleared rapidly
      from the blood, drug persisted in the liver and spleen for at least 48 h after
      administration of a dose of LIC. We attribute the enhanced activity of LIC to the
      concentration and persistence of active drug in the infected organs. Our results
      confirm the fact that ciprofloxacin is effective therapy for systemic salmonella
      infection and show that LIC is even more effective than aqueous ciprofloxacin in
      our model.

PMID- 8285609
TI  - Double-blind, comparative study of rufloxacin once daily versus amoxicillin three
      times a day in treatment of outpatients with exacerbations of chronic bronchitis.
AB  - In a double-blind, randomized, multicenter study, the efficacy and safety of two
      dosage schedules of rufloxacin once daily were compared with those of amoxicillin
      three times a day in the treatment of 192 outpatients with exacerbations of
      chronic bronchitis. Rufloxacin was given as a single oral dose of 400 mg on day 1
      and single daily doses of 200 mg on the subsequent 9 days (n = 64) or as 300 mg
      on day 1 and then 150 mg daily for 9 days (n = 63); amoxicillin was given as 500
      mg orally three times a day for 10 days (n = 65). Clinical and bacteriological
      assessments were carried out before treatment, between study days 3 and 5, and at
      days 1 and 8 after treatment. Pretreatment cultures were positive for 139
      patients, the most frequently isolated pathogens being Streptococcus pneumoniae,
      Moraxella catarrhalis, and Haemophilus influenzae. Clinical success rates were
      comparable in the three groups (94, 95, and 98%, respectively), as were
      bacteriological success rates at the end of treatment (93, 95, and 91%,
      respectively) and at follow-up (88, 95, and 98%, respectively). The power to
      detect a significant 15% difference in cure rates was 74.9%. Follow-up
      bacteriological failures from pneumococcal infection were 18% in both rufloxacin
      groups combined and 5% in the amoxicillin group. The 200-mg dose regimen achieved
      average steady-state concentrations in plasma higher than did the 150-mg dose
      regimen (3.75 versus 2.72 micrograms/ml). Adverse events occurred in 11 and 13
      patients, respectively, on rufloxacin and 8 on amoxicillin. This study shows that
      rufloxacin once daily ay be a possible option for the treatment of acute
      exacerbations of chronic bronchitis. The 200-mg daily oral dose preceeded by a
      loading dose of 400 mg displays a better pharmacokinetic profile than the lower
      dose.

PMID- 8285610
TI  - Efficacy of itraconazole solution in a rabbit model of invasive aspergillosis.
AB  - The efficacy of an itraconazole-cyclodextrin solution against Aspergillus
      fumigatus was assessed in an immunosuppressed, temporarily leukopenic rabbit
      model of invasive aspergillosis and compared with that of amphotericin B. Oral
      itraconazole solution at dosages of 20 and 40 mg/kg/day improved survival as
      compared with that of controls. Itraconazole (40 mg/kg/day) not only improved
      survival and reduced antigen levels but also significantly eradicated A.
      fumigatus from tissues and was as effective as amphotericin B in these studies.
      The higher dose of itraconazole produced higher levels in serum, which correlated
      with improved efficacy of the drug. This itraconazole-cyclodextrin solution was
      well absorbed and was effective in the treatment of experimental invasive
      aspergillosis; it demonstrates the potential of this class of agents in improving
      therapy for invasive aspergillosis.

PMID- 8285611
TI  - Characterization of glycopeptide-resistant enterococci from U.S. hospitals.
AB  - We examined 105 clinical isolates of glycopeptide-resistant enterococci collected
      from 31 U.S. hospitals in 14 states during May 1988 to July 1992. The isolates
      included 82 Enterococcus faecium, 8 E. faecalis, 6 Enterococcus spp., 5 E.
      gallinarum, 3 E. casseliflavus, and 1 E. raffinosus. The isolates were
      categorized into the following four phenotypes of glycopeptide resistance on the
      basis of their MIC patterns: (i) 70 VanA (vancomycin [Vm] MIC, > or = 64
      micrograms/ml; teicoplanin [Tei] MIC, 16 to > or = 128 micrograms/ml), (ii) 26
      VanB (Vm MIC, 16 to 1,024 micrograms/ml; Tei MIC, < or = 2 micrograms/ml), (iii)
      5 VanC (Vm MIC, 4 to 16 micrograms/ml; Tei MIC, < or = 2 micrograms/ml) in E.
      gallinarum, and (iv) 3 E. casseliflavus and 1 E. raffinosus isolates for which Vm
      MICs were 4 to 16 micrograms/ml and Tei MICs were < or = 1 micrograms/ml were
      called unclassified. Of the 101 isolates with the VanA, VanB, and VanC
      phenotypes, 99 were confirmed by production of a specific 1,030-, 433-, or 796-bp
      polymerase chain reaction product, respectively, and hybridization with the
      respective gene probe. The vanA gene was also detected in the E. raffinosus
      isolate for which the Vm MIC was 16 micrograms/ml and the Tei MIC was 1
      microgram/ml. The vanA gene was located on either a 34- or a 60-kb plasmid in all
      of the U.S. isolates examined. Pulsed-field gel electrophoresis demonstrated both
      intrahospital and interhospital diversity among Vmr enterococci in the United
      States and was more useful than plasmid analysis for epidemiologic studies.

PMID- 8285612
TI  - Uptake of azithromycin by human monocytes and enhanced intracellular
      antibacterial activity against Staphylococcus aureus.
AB  - The uptake of azithromycin by human monocytes and the intracellular antibacterial
      activity of azithromycin against Staphylococcus aureus were investigated. With an
      extracellular pH of 6.9, the maximum intracellular concentration of azithromycin
      in monocytes was about six times the extracellular concentration. The half-life
      for diffusion was 44 min. The results support the view that no active transport
      is involved in the intracellular accumulation of azithromycin. In cell-free
      medium, the maximum effect of azithromycin on S. aureus was bacteriostasis, which
      was achieved at a concentration of 5 mg/liter. In contrast, concentrations
      greater than 1.5 mg of azithromycin per liter were bactericidal for S. aureus
      ingested by monocytes. The difference in maximum growth inhibition on S. aureus
      for the two conditions was 0.1.68 h-1 (95% confidence interval, 0.128 to 0.208).
      The concentration of the drug that achieved 50% of the maximum effect was 0.434
      mg/liter for both conditions. The enhancement of the effect on S. aureus ingested
      by monocytes suggests that the intracellular environment in human monocytes
      favors the antibacterial action of azithromycin. Enhancement of the antibacterial
      activity of azithromycin was not observed with granulocytes.

PMID- 8285614
TI  - Stereoselective renal tubular secretion of carbenicillin.
AB  - The stereoselective disposition of carbenicillin epimers was studied in healthy
      human volunteers. There was a difference between the two epimers in the extent of
      plasma protein binding in vitro, with the unbound fraction of the R epimer being
      greater than that of the S epimer. Renal clearance (CLR) of each epimer was
      greater than the glomerular filtration rate, suggesting renal tubular secretion
      of both epimers. Although the CLR was greater for the R epimer, renal tubular
      secretion was greater for the S epimer. When probenecid was coadministered, the
      CLR of each epimer was significantly reduced and was approximately equal to the
      glomerular filtration rate. The difference in CLR between the two epimers was
      simply due to differences in plasma protein binding. The observations in the
      present study suggest that both carbenicillin epimers are secreted by an organic
      anion transport system in the renal proximal tubule in humans and that the two
      epimers may be distinguished in the secretion process, resulting in the
      differences in the secretion rates.

PMID- 8285613
TI  - Activities of antimicrobial agents against clinical isolates of Mycobacterium
      haemophilum.
AB  - Mycobacterium haemophilum, first described in 1978, can cause severe infections
      of skin, respiratory tract, bone, and other organs of immunocompromised patients.
      There is no standardized antimicrobial susceptibility test, and for the 27
      reported cases, a variety of test methods have been used. This paper reports the
      in vitro test results for 17 isolates of M. haemophilum recovered from 12
      patients in the New York City area. MICs of 16 antimicrobial agents were
      determined in microtiter trays containing Middlebrook 7H9 broth plus 60 microM
      hemin, inoculated with 10(6) CFU of the organism per ml and incubated at 30
      degrees C for 10 days. Ethambutol, ethionamide, tetracycline, cefoxitin, and
      trimethoprim-sulfamethoxazole were inactive against initial isolates from the 12
      patients. Isoniazid was weakly active with a MIC for 50% of strains tested
      (MIC50) of 8 micrograms/ml and a MIC90 of > 32 micrograms/ml. Three quinolones,
      ciprofloxacin, ofloxacin, and sparfloxacin, were moderately active with MIC50s of
      2 to 4 micrograms/ml and MIC90s of 4 to 8 micrograms/ml. Amikacin and clofazamine
      were active with MIC90s of 4 and 2 micrograms/ml, respectively. Clarithromycin
      was the most active macrolide with a MIC90 of < or = 0.25 microgram/ml. The MIC90
      of azithromycin was 8 micrograms/ml, and the MIC90 of erythromycin was 4
      micrograms/ml. The rifamycins were active with a MIC90 of 1 microgram/ml for
      rifampin and one of < or = 0.03 micrograms/ml for rifabutin. For a second isolate
      from the skin of one patient and a isolate from an autopsy culture of the spleen
      of a second patient, MICs of rifampin and rifabutin were > 16 microgram/ml,
      whereas initial isolates were inactivated by low concentrations of the
      rifamycins. Both patients had been treated for several months with several
      antimicrobial agents, including a rifamycin.

PMID- 8285615
TI  - Therapy of experimental murine brucellosis with streptomycin alone and in
      combination with ciprofloxacin, doxycycline, and rifampin.
AB  - The in vivo efficacy of streptomycin (STR), doxycycline (DOX), rifampin (RIF),
      ciprofloxacin (CIP), and their combinations was evaluated for a Brucella
      melitensis experimental infection in a mouse model. Animals were infected with 2
      x 10(4) to 4 x 10(4) CFU of B. melitensis intraperitoneally on day 0 and were
      randomized to receive, starting on day 7, STR alone at 75, 150, or 300 mg/kg of
      body weight per day intraperitoneally or DOX at 6 mg/kg/day orally, RIF at 3
      mg/kg/day orally, or CIP at 200 mg/kg/day orally, each of the last three drugs
      alone or in combination with STR at 75, 150, or 300 mg/kg/day, for 14 days.
      Therapy failure (defined as nonsterile spleens) was observed in all animals
      treated with STR at all doses and with CIP given as monotherapy. Mean log CFU
      isolated from the spleens remaining infected following monotherapy with STR or
      CIP were not different from those in control mice. RIF at a low dose did not have
      an effect on cure rates; however, a reduction in CFU relative to the CFU in
      untreated animals was obtained. DOX at low levels achieved a 35% cure rate and a
      reduction in CFU in animals not cured. All animals treated with DOX or RIF
      combined with any STR dose were cured, but none of the animals receiving the STR
      CIP combinations was cured, and the splenic CFU remained similar to those in the
      controls. These results demonstrate that the combinations DOX-STR and RIF-STR are
      synergistic against B. melitensis, while the combination STR-CIP is indifferent
      and ineffective in the management of acute murine brucellosis. The results also
      appear to support the clinical superiority of combination drug therapy over
      monotherapy.

PMID- 8285616
TI  - Development of halofantrine resistance and determination of cross-resistance
      patterns in Plasmodium falciparum.
AB  - Intermittent exposure to halofantrine (HF) of both chloroquine-susceptible
      (T9.96) and chloroquine-resistant (K1) isolates of Plasmodium falciparum in vitro
      resulted in a rapid reduction in susceptibility to HF. After 6 months, the 50%
      inhibitory concentration (IC50) of HF, determined with [G-3H]hypoxanthine
      incorporation as a marker, increased ninefold for the chloroquine-resistant (K1)
      isolate and threefold for the cloned chloroquine-susceptible (T9.96) isolate, the
      derived isolates being termed the K1HF3 and T9.96HF4 isolates, respectively. By
      microscopic examination of cultured erythrocytes, we determined that there was a
      fivefold increase in the IC50 for isolate T9.96HF4. The responses of the parental
      isolates and the HF-resistant isolates to chloroquine, mefloquine, quinine,
      amodiaquine, qinghaosu, and pyrimethamine were determined. In comparison with the
      parental K1 isolate, HF-resistant isolate K1HF3 was significantly more
      susceptible to the action of chloroquine and exhibited a significantly reduced
      susceptibility to quinine and mefloquine. The other HF-resistant isolate,
      T9.96HF4, showed no alteration in susceptibility to amodiaquine or chloroquine
      but a significantly decreased susceptibility to mefloquine. Resistance was stable
      in the two isolates, both in the absence of drug pressure or when kept frozen in
      liquid nitrogen. In contrast, continuous exposure to HF had no effect on the
      susceptibility of the parasites to this drug above HF concentrations of 3.2 x 10(
      9) M.

PMID- 8285617
TI  - Therapy of multidrug-resistant tuberculosis: lessons from studies with mice.
AB  - The activities of antituberculosis agents were evaluated in a murine tuberculosis
      model using a drug-resistant isolate. A multidrug-resistant clinical isolate from
      a recent outbreak of tuberculosis in the New York State correctional system was
      used for infection. Approximately 10(7) viable Mycobacterium tuberculosis ATCC
      49967 (strain CNL) organisms were given intravenously to 4-week-old female
      outbred mice. Treatment was started 1 day after infection and given for 4 weeks.
      Spleens and lungs were homogenized, and viable cell counts were determined.
      Statistical analysis indicated that ethionamide, sparfloxacin, ofloxacin,
      capreomycin, clarithromycin, and clofazimine are active in the murine test system
      with this multidrug-resistant tuberculosis isolate. Sparfloxacin is the most
      active quinolone. Despite in vitro resistance, isoniazid has moderate activity.
      In vitro susceptibility data coupled with evaluation of agents against drug
      resistant isolates in the murine system should provide information necessary to
      design clinical trials for treatment of infections with these organisms.

PMID- 8285618
TI  - In vitro activity of Bay y 3118, a new quinolone.
AB  - MICs of Bay y 3118, ciprofloxacin, ofloxacin, clarithromycin, azithromycin,
      cefuroxime, amoxicillin-clavulanate, and trimethoprim-sulfamethoxazole for 878
      recent clinical isolates were determined by broth microdilution methods. Among
      the three quinolones, Bay y 3118 was the most active against Haemophilus
      influenzae, Moraxella catarrhalis, Acinetobacter baumannii, Xanthomonas
      maltophilia, gram-positive cocci, and anaerobes; MICs for 50% of the strains
      (MIC50s) and MIC90s were < or = 0.015 and < or = 0.015, < or = 0.015 and < or =
      0.015, 0.03 and 2, 0.25 and 0.5, 0.06 and 1, and 0.12 and 0.25 micrograms/ml,
      respectively. For gram-positive cocci and anaerobes, these values were 16- to 32
      fold (4 to 5 log2 dilution steps) lower than those for ciprofloxacin and
      ofloxacin. Bay y 3118 was similar in activity to ciprofloxacin and more active
      than ofloxacin against members of the family Enterobacteriaceae and Pseudomonas
      aeruginosa; Bay y 3118 MIC50s and MIC90s were 0.03 and 0.25 and 0.5 and 8
      micrograms/ml, respectively. Scattergrams and regression analyses comparing
      quinolone MICs indicated that, despite differences in activity, organisms
      relatively susceptible to one were relatively susceptible to all and organisms
      relatively resistant to one were relatively resistant to all. However, the
      greater in vitro activity of Bay y 3118 was most pronounced against relatively
      resistant organisms. Pending pharmacokinetic and safety data for Bay y 3118,
      there is reasonable anticipation that its enhanced activity against gram-positive
      cocci and anaerobes would broaden the clinical utility of the quinolone class of
      antimicrobial agents.

PMID- 8285619
TI  - Toxoplasma gondii: susceptibility and development of resistance to anticoccidial
      drugs in vitro.
AB  - Anticoccidial drugs were evaluated for activity and for the development of
      resistance in a model of Toxoplasma gondii growing in human fibroblast cultures.
      Of 13 anticoccidial drugs tested, 9 had selective antitoxoplasma activity (50%
      inhibitory concentration, in micrograms per milliliter): decoquinate (0.005),
      arprinocid-N-oxide (0.015), robenidine (0.03), the aryl triazine CP-25,415 (0.2),
      toltrazuril (0.4), clopidol (1), dinitolmide (Zoalene; Dow) (10), and the
      carboxylic acid ionophores monensin (0.001) and salinomycin (0.04).
      Glycarbylamide, amprolium, nicarbazin, and the 6-(p-bromophenoxy)-7-chloro analog
      of halofuginone (Stenorol; Roussel-UCLAF) (CP-63,567) were toxic for the
      fibroblasts. Since Eimeria tenella has a similar drug susceptibility profile,
      anticoccidial drugs can be viewed as a potential source of new antitoxoplasma
      therapies. The development of resistance has limited the usefulness of most of
      these drugs as anticoccidial agents; in coccidia, resistance to all except the
      ionophores occurs readily in vivo. We explored the development of resistance in
      T. gondii by attempting to select mutants in vitro from parasites mutagenized
      with ethylnitrosourea. Mutants that had 20- to 50-fold-reduced susceptibility to
      decoquinate, arprinocid-N-oxide, and CP-25,415 were obtained. Ionophore-resistant
      T. gondii mutants were also selected in vitro; however, there was only a twofold
      difference in susceptibility between these mutants and the wild type. For three
      drugs (clopidol, robenidine, and toltrazuril), we were unable to select resistant
      mutants. For experimental anticoccidial drugs, there is currently no in vitro
      method for assessing the risk of development of resistance in Eimeria species.
      Our results suggest that T. gondii may offer a useful surrogate for this
      assessment.

PMID- 8285620
TI  - In vitro and in vivo activities of the hydroxynaphthoquinone atovaquone alone or
      combined with pyrimethamine, sulfadiazine, clarithromycin, or minocycline against
      Toxoplasma gondii.
AB  - The efficacy of atovaquone alone or combined with pyrimethamine, sulfadiazine,
      clarithromycin, and minocycline was examined in vitro and in a murine model of
      acute toxoplasmosis. In vitro studies were performed with MRC5 fibroblast tissue
      cultures, with quantification of Toxoplasma growth by an enzyme-linked
      immunosorbent assay. For in vivo studies, mice were acutely infected
      intraperitoneally with 10(4) tachyzoites of the virulent RH strain and then
      treated perorally for 10 days from day 1 postinfection. The following drug
      regimens were investigated: atovaquone at 100 and 50 mg/kg of body weight per day
      and the combinations of atovaquone at 50 mg/kg with sulfadiazine at 200 mg/kg,
      pyrimethamine at 12.5 mg/kg, clarithromycin at 200 mg/kg, or minocycline at 50
      mg/kg. Efficacy was assessed by determination of survival rates and sequential
      determination of parasite burdens in blood, brain, and lungs. In vitro,
      atovaquone inhibited Toxoplasma growth at a concentration of > or = 0.02
      mg/liter; the 50% inhibitory concentration was estimated to be 0.023 mg/liter. No
      synergistic effect was observed when it was combined with sulfadiazine,
      clarithromycin, or minocycline, whereas a significant antagonistic effect was
      noted for the combination of atovaquone with pyrimethamine. In vivo,
      administration of atovaquone at 100 or 50 mg/kg/day for 10 days resulted in
      prolonged survival compared with that in untreated mice; this survival was
      associated with a reduction of parasite burdens in blood and tissues during the
      course of treatment. The combinations of atovaquone with pyrimethamine,
      clarithromycin, or sulfadiazine were more efficient than each drug administered
      alone, in terms of survival, but parasite burdens in blood and organs were not
      reduced compared with those in mice treated with any of the agents alone. These
      experimental results confirmed the activity of atovaquone against Toxoplasma
      gondii, but no marked improvement in efficacy was observed in vitro and in vivo
      when this drug was combined with pyrimethamine, sulfadiazine, minocycline, or
      clarithromycin.

PMID- 8285621
TI  - Antibiotic preparations contain DNA: a source of drug resistance genes?
AB  - Fluorescence measurements and polymerase chain reaction amplification of
      streptomycete 16S ribosomal DNA sequences were used to show that a number of
      antibiotic preparations employed for human and animal use are contaminated with
      chromosomal DNA of the antibiotic-producing organism. The DNA contains
      identifiable antibiotic resistance gene sequences; the uptake of this DNA by
      bacteria and its functional incorporation into bacterial replicons would lead to
      the generation of antibiotic resistance determinants. We propose that the
      presence of DNA encoding drug resistance in antibiotic preparations has been a
      factor in the rapid development of multiple antibiotic resistance in bacteria.

PMID- 8285622
TI  - Mechanism of efficient elimination of protein D2 in outer membrane of imipenem
      resistant Pseudomonas aeruginosa.
AB  - Most imipenem-resistant Pseudomonas aeruginosa isolates produce an
      immunologically undetectable level of protein D2 (OprD2). To study the efficient
      elimination of the protein, we selected 23 independent imipenem-resistant mutants
      from a strain harboring the plasmid carrying cloned oprD and having a mutation in
      chromosomal oprD. All these oprD/oprD (plasmid/chromosomal) mutants expressed
      undetectable levels of OprD2, as shown from an assay by the immunoblotting
      method. Restriction maps of the DNAs from all 23 mutant plasmids could be divided
      into two groups. Restriction mapping and sequencing analysis of DNA from one
      representative plasmid from each group showed that both mutant oprD genes had a
      deletion. One had an 11-bp deletion in the coding region generating a frameshift
      mutation and a premature termination codon. Another had a large deletion
      encompassing the upstream site of its putative promoter region through the coding
      region. Northern blotting analysis showed that the gene with the 11-bp deletion
      was transcribed to about 1.5 kb of mRNA, but the gene with the large deletion
      produced undetectable RNA complementary to the oprD DNA probe. Since we analyzed
      only plasmid-borne oprD, we cannot exclude the possibility that the imipenem
      resistance caused by the chromosomal mutation is by a different mechanism(s). It
      is suggested, yet, that clear elimination of OprD2 from most imipenem-resistant
      P. aeruginosa isolates is due to efficient selection of the oprD deletion
      mutants.

PMID- 8285623
TI  - Cloning and characterization of the endogenous cephalosporinase gene, cepA, from
      Bacteroides fragilis reveals a new subgroup of Ambler class A beta-lactamases.
AB  - Bacteroides fragilis CS30 is a clinical isolate resistant to high concentrations
      of benzylpenicillin and cephaloridine but not to cephamycin or penem antibiotics.
      beta-Lactam resistance is mediated by a chromosomally encoded cephalosporinase
      produced at a high level. The gene encoding this beta-lactamase was cloned from
      genomic libraries constructed in Escherichia coli and then mated with B. fragilis
      638 for identification of ampicillin-resistant (Apr) strains. Apr transconjugants
      contained a nitrocefin-reactive protein with the physical and enzymatic
      properties of the original CS30 isolate. The beta-lactamase gene (cepA) was
      localized by deletion analysis and subcloned, and its nucleotide sequence was
      determined. The 903-bp cepA open reading frame encoded a 300-amino-acid precursor
      protein (predicted molecular mass, 34,070 Da). A beta-lactamase-deficient mutant
      strain of B. fragilis 638 was constructed by insertional inactivation with the
      cepA gene of CS30, demonstrating strict functional homology between these
      chromosomal beta-lactamase genes. An extensive comparison of the CepA protein
      sequence by alignment with other beta-lactamases revealed the strict conservation
      of at least four elements common to Ambler class A. A further comparison of the
      CepA protein sequence with protein sequences of beta-lactamases from two other
      Bacteroides species indicated that they constitute their own distinct subgroup of
      class A beta-lactamases.

PMID- 8285624
TI  - Use of intravenous rifampin in neonates with persistent staphylococcal
      bacteremia.
AB  - Ten neonates with persistent staphylococcal bacteremia (positive blood cultures
      for > or = 5 days despite appropriate antibiotic therapy) received intravenous
      (i.v.) rifampin in combination with vancomycin with or without aminoglycoside.
      Their mean birth weight and length of gestation were 900 g and 27 weeks,
      respectively. Their ages at the time of infection ranged from 6 to 64 days (mean,
      26 days). The staphylococcal isolates were methicillin-resistant Staphylococcus
      aureus (five isolates), methicillin-susceptible S. aureus (two isolates), and
      coagulase-negative staphylococci (three isolates). The mean number of bacteremia
      days prior to administration of i.v. rifampin was 8.3 (range, 5 to 15 days),
      despite a mean peak vancomycin concentration of 33 micrograms/ml. The dosing of
      rifampin varied from 2.5 to 10 mg/kg of body weight every 12 h. The mean duration
      of the rifampin course was 9.7 days (range, 3 to 16 days). Of the 10 neonates, 8
      (80%) had sterile blood cultures within 24 h, 1 (10%) had a sterile blood culture
      within 48 h, and 1 (10%) had a sterile blood culture within 5 days of being
      placed on i.v. rifampin. No adverse effects were noted in this small group of
      infants. Seven of the 10 neonates survived; three died from unrelated
      complications. The MIC ranges of amikacin, vancomycin, and rifampin for the
      isolates were 2.0 to 16, 0.5 to 2.0, and 0.0013 to 0.04 micrograms/ml,
      respectively. We also studied eight infants, with a mean age of 23 days, who were
      receiving i.v. or oral rifampin at a dose of 10 mg/kg/day. For i.v.
      administration, the peak serum concentration of rifampin (mean +/- standard
      deviation) was 4.02 +/- 1.22 microgram/ml. The mean trough level at 12 h
      postifution was 1.11 +/- 0.48 micrograms/ml. For oral administration, the
      concentrations of rifampin in serum ranged from 0.59 to 2.86 micrograms/ml (mean,
      1.86 +/- 0.96 microgram/ml) at 2 h postingestion, increasing to a peak
      concentration of 2.8 micrograms/ml at 8 h postingestion. The mean 12-h
      postingestion level was 0.77 +/- 0.03 microgram/ml. From the study of this
      limited series of neonates, rifampin appears to be a safe and effective addition
      to therapy when staphylococcal bacteremia is persistent despite vancomycin
      treatment.

PMID- 8285625
TI  - Response to antifungal therapy by human immunodeficiency virus-infected patients
      with disseminated Penicillium marneffei infections and in vitro susceptibilities
      of isolates from clinical specimens.
AB  - Eighty-six patients with laboratory evidence of human immunodeficiency virus
      infection presented to Chiang Mai University Hospital in Chiang Mai, Thailand,
      between 1 June 1990 and 30 June 1992 with systemic infection caused by the
      dimorphic fungus Penicillium marneffei. Thirty isolates of P. marneffei from
      clinical specimens from these patients were tested for their in vitro
      susceptibilities to amphotericin B, 5-fluorocytosine, miconazole, ketoconazole,
      itraconazole, and fluconazole. P. marneffei was highly susceptible to miconazole,
      itraconazole, ketoconazole, and 5-fluorocytosine. Amphotericin B showed
      intermediate antifungal activity, while fluconazole was the least active; some
      strains of the fungus were resistant to fluconazole. The clinical and
      microbiological responses correlated with the overall patterns of in vitro
      susceptibility to the azoles, whereas results with amphotericin B were more
      difficult to assess. Antibiotic failures of initial therapy occurred in 8 of 35
      (22.8%) patients treated with amphotericin B, 3 of 12 (25%) patients treated with
      itraconazole, and 7 of 11 (63.6%) patients treated with fluconazole. Itraconazole
      or ketoconazole should be considered to be the drug of first choice in the
      treatment of mild to moderately severe P. marneffei infection. Parenteral therapy
      with amphotericin B may be required for seriously ill patients. Since at least 12
      patients who responded to initial therapy relapsed within 6 months regardless of
      initial antifungal therapy, maintenance oral therapy with itraconazole or
      ketoconazole may be necessary.

PMID- 8285626
TI  - In vitro and in vivo antifungal activities of D0870, a new triazole agent.
AB  - In vitro and in vivo antifungal activities of D0870 were evaluated in comparison
      with those of fluconazole. D0870, which is the R-enantiomer of ICI195,739, was
      found to be the mycologically active enantiomer by comparing the activities of
      D0870 with those of M16355 (S-enantiomer of ICI195,739). D0870 showed a broad
      spectrum of antifungal activity and MICs and minimum antibiotic concentrations 4-
      to 2,000-fold lower in synthetic amino acid medium (fungal) agar than those of
      fluconazole for various fungi. Although MICs of D0870 were affected by variation
      of the test conditions, such as type of medium, inoculum size of fungi,
      supplementation with fetal bovine serum, and pH of medium, they were consistently
      much lower than those of fluconazole under any condition. In vivo activities of
      D0870 in the systemic infection models with Candida albicans, Cryptococcus
      neoformans, and Aspergillus fumigatus in normal mice and in the mice
      immunosuppressed with cyclophosphamide or cortisone acetate were 2- to 7-fold and
      3- to 89-fold greater than those of fluconazole, respectively. In these infection
      models in immunosuppressed mice, the therapeutic efficacy of D0870 was almost
      equivalent to that in normal mice, whereas the efficacy of fluconazole was 2- to
      50-fold lower than that in normal mice.

PMID- 8285627
TI  - Interleukin-6, gamma interferon, and tumor necrosis factor receptors in typhoid
      fever related to outcome of antimicrobial therapy.
AB  - To study mechanisms of antibiotic effects in typhoid fever, levels of interleukin
      6 (IL-6), gamma interferon (IFN-gamma), and cytokine receptors (tumor necrosis
      factor receptor [TNF-R] p55 and TNF-R p75) were measured in the plasma of 29
      adult Nepalese with culture-positive typhoid fever before therapy and on days 4
      and 15 after start of therapy with either ceftriaxone at 2 g/day for 3 days or
      chloramphenicol at 50 mg/kg of body weight per day for 14 days. Bacteriologic
      cure was defined as blood cultures testing negative on days 4 and 15 after start
      of therapy; clinical cure was defined as symptomatic improvement within 5 days
      after start of therapy and absence of relapse. Clinical and bacteriologic cures
      occurred in 24 patients. There were two clinical failures, two patients who
      failed to complete therapy because of leukopenia, and one relapse. Mean levels
      before therapy were elevated compared with those in healthy controls (IL-6, 11.4
      pg/ml; IFN-gamma, 1.3 ng/ml; TNF-R p55, 3.8 ng/ml; and TNF-R p75, 6.1 ng/ml) and
      fell progressively during and after therapy. For six patients (three in each
      treatment group) who showed prolonged fever (> 5 days) or relapse, mean levels of
      IL-6 and TNF-R p55 before therapy (29.5 pg/ml and 6.1 ng/ml, respectively) and on
      day 4 (17.7 pg/ml and 4.0 ng/ml) were significantly greater than corresponding
      means for 23 patients who showed early defervescence (on admission, 6.7 pg/ml and
      3.3 ng/ml, and on day 4, 1.8 pg/ml and 2.7 ng/ml, P < .05). These results
      indicate that the concentrations of plasma cytokines and their receptors are
      elevated in typhoid fever and that these concentrations can be useful in
      predicting outcome.

PMID- 8285628
TI  - High-level penicillin resistance and penicillin-gentamicin synergy in
      Enterococcus faecium.
AB  - Thirty-seven Enterococcus faecium strains with different levels of penicillin
      susceptibility were studied in time-kill experiments with a fixed concentration
      (5 micrograms/ml) of gentamicin combined with different penicillin concentrations
      (6 to 600 micrograms/ml). Synergy was defined as a relative decrease in counts of
      greater than 2 log10 CFU per milliliter after 24 h of incubation when the
      combination of the antibiotics was compared with its most active component alone.
      The minimal synergistic penicillin concentrations found were 6 micrograms/ml for
      16 of 16 strains for which penicillin MICs were < or = 25 micrograms/ml, 20 to
      100 micrograms/ml for 14 of 17 strains for which penicillin MICs were 50 to 200
      micrograms/ml, and 200 to 500 micrograms/ml for 4 of 4 strains for which MICs
      penicillin were > 200 micrograms/ml. Penicillin-gentamicin synergy was observed
      even in high-level penicillin-resistant E. faecium strains at penicillin
      concentrations close to one-half the penicillin MIC. The possibility of treating
      infections caused by high-level penicillin-resistant E. faecium strains with
      penicillin-gentamicin combinations in particular cases may depend on the
      penicillin levels attainable in vivo.

PMID- 8285629
TI  - Teicoplanin-resistant Staphylococcus aureus expresses a novel membrane protein
      and increases expression of penicillin-binding protein 2 complex.
AB  - In the recent clinical trials of teicoplanin therapy of endocarditis caused by
      Staphylococcus aureus, at least one instance of the emergence of teicoplanin
      resistant strains during therapy has been reported (G.W. Kaatz, S. M. Seo, N. J.
      Dorman, and S. A. Lerner, J. Infect. Dis 162:103-108, 1990). We have confirmed,
      using conventional electrophoresis of EcoRI-digested chromosomal DNA and pulsed
      field gel electrophoresis of SmaI-digested chromosomal DNA, that the resistant
      strain (12873) (MIC, 16 micrograms/ml) is genetically very similar to the
      susceptible parent (12871) (MIC, 4 micrograms/ml). Kaatz et al. were able to
      select spontaneous teicoplanin-resistant mutants (10(-9)), suggesting that a
      single gene might be involved. We have shown that the mutation is highly stable
      during growth in the absence of teicoplanin. Using Tn551, we have selected
      insertion mutants of 12873 that become teicoplanin susceptible. We have examined
      a number of aspects of cell wall physiology in strains 12871 and 12873 and the
      teicoplanin-susceptible Tn551 mutants of 12873. 12873 was more susceptible to
      lysostaphin lysis than 12871 and the susceptible Tn551 derivatives of 12873.
      Autolysis in phosphate buffer (pH 7.5) and cell wall turnover rates were similar
      in 12871 and 12873. An analysis of membrane proteins revealed the expression of a
      ca. 35-kDa protein and increased expression of both polypeptides of penicillin
      binding protein (PBP) 2 (PBP2) in 12873 relative to 12871 and the Tn551 mutants
      of 12873. This increased expression was not related to PBP2', since both strains
      were susceptible to oxacillin in 2% NaCl (MIC, < or = 0.25 microgram/ml) and
      cellular DNA from neither strain hybridized with a specific mec gene probe. Two
      independent Tn551 inserts have been mapped to a ca. 117-kb SmaI fragment of the
      chromosome. These data suggest the possibility that the mutation resulting in
      resistance to teicoplanin involves the regulation of expression of both
      polypeptides of PBP2 and a 35-kDa membrane protein.

PMID- 8285630
TI  - Critical hydrogen bonding by serine 235 for cephalosporinase activity of TEM-1
      beta-lactamase.
AB  - The role of Ser-235 in the catalytic mechanism of the TEM-1 beta-lactamase has
      been explored by the study of a mutant enzyme in which Ser-235 has been
      substituted by alanine (Ala-235 mutant enzyme). A comparative kinetic analysis of
      both the wild-type and the Ala-235 TEM-1 enzymes revealed little effect of this
      substitution of residue 235 on the turnover of penicillins but a greater effect
      on the turnover of cephalosporins. Susceptibility testing of Escherichia coli
      strains harboring the wild-type TEM-1 beta-lactamase and the Ala-235 mutant
      enzyme revealed an effect of the mutation similar to that observed in the
      enzymological studies. The MICs of two representative cephalosporins for the
      strain containing the mutant enzyme were much lower than those for the isogenic
      strain bearing the wild-type TEM-1 beta-lactamase. On the other hand, the strain
      with the mutant enzyme was still highly resistant to penicillins.

PMID- 8285631
TI  - Susceptibilities of Norwegian Candida albicans strains to fluconazole: emergence
      of resistance. The Norwegian Yeast Study Group.
AB  - All Candida albicans isolates in Norwegian microbiological laboratories in 1991
      judged clinically important (except vaginal isolates) were collected. The
      isolates were tested for susceptibility to fluconazole with an agar dilution test
      and a commercially available agar diffusion test. A total of 212 strains (95%)
      were susceptible to fluconazole, and MICs for most of the strains (92%) were < or
      = 1.56 micrograms/ml. The agar diffusion test using a 15-micrograms tablet and a
      48-h incubation period separated resistant from susceptible strains with a wide
      margin. The only exception was a strain for which the MIC was 6.25 micrograms/ml.
      The difference in zone size between the resistant and the susceptible populations
      of strains was 11 mm. Accordingly, it appears that the agar diffusion test is an
      appropriate method for detecting fluconazole resistance. The 12 fluconazole
      resistant isolates originated from eight AIDS patients with oral or esophageal
      Candida infections. Seven of the patients had been given fluconazole for 1 month
      or more, often as self medication. Four had infections that were clinically
      resistant to fluconazole; one additional patient responded only when the dose was
      increased. All isolates recovered from these patients were analyzed by multilocus
      enzyme electrophoresis. The 12 C. albicans isolates belonged to five
      electrophoretic types, but three of four patients attending one hospital had
      isolates belonging to one electrophoretic type. One possible explanation for this
      finding could be that a nosocomial spread of resistant strains has occurred.

PMID- 8285632
TI  - Correlation of in vitro fluconazole resistance of Candida isolates in relation to
      therapy and symptoms of individuals seropositive for human immunodeficiency virus
      type 1.
AB  - Yeast strains isolated from the oropharynx of 87 consecutive patients infected
      with human immunodeficiency virus type 1 were examined for in vitro
      susceptibility to fluconazole. Candida albicans was isolated from 73 patients.
      Fifty-one patients had received antifungal therapy in the month preceding the
      yeast infection. Thirty-two patients had symptomatic oropharyngeal candidiasis.
      The MICs were correlated with azole use and with clinical symptoms and signs.
      Although there is overlap between groups, in vitro testing identified a large
      group of patients for whose yeast isolates the fluconazole MICs were high and who
      remained symptomatic while receiving azole therapy. This study supports the
      ability of in vitro testing to predict the clinical outcome of mucosal fungal
      infections. The study also demonstrates that azole resistance of oropharyngeal
      yeasts is a common problem in patients infected with human immunodeficiency virus
      type 1 and that this azole resistance has clinical relevance.

PMID- 8285633
TI  - Evaluation of activity of temafloxacin against Bacteroides fragilis by an in
      vitro pharmacodynamic system.
AB  - An in vitro pharmacodynamic system has been successfully adapted to simulate in
      vivo antimicrobial pharmacokinetics under anaerobic conditions. This system was
      used to perform time-kill kinetic studies which were designed to compare the
      activity of temafloxacin to ciprofloxacin and cefotetan against two strains of
      Bacteroides fragilis (ATCC 25285 and ATCC 23745). All experiments were performed
      as single-dose, 24-h, duplicate runs. Starting bacterial inocula of 10(7) CFU/ml
      were exposed to starting antimicrobial concentrations of 5 micrograms of
      temafloxacin per ml, 5 micrograms of ciprofloxacin per ml, and 100 micrograms of
      cefotetan per ml. Terminal half-lives of 8, 4, and 4 h were simulated for each
      antimicrobial agent. Temafloxacin was rapidly bactericidal against B. fragilis.
      Ciprofloxacin was not bactericidal (< 3 log10 unit decline in bacterial numbers)
      to either strain of B. fragilis. Cefotetan was bactericidal (> or = 3 log10 unit
      decline in bacterial numbers) to each strain but killed at a slower rate than
      temafloxacin. Times to 3 log10 unit declines of strain ATCC 25285 were 2, 4, and
      > 24 h, whereas those of strain ATCC 23745 were 4, 4, and > 24 h for
      temafloxacin, cefotetan, and ciprofloxacin, respectively. Total logarithmic
      declines of strain ATCC 25285 were > 4.5, > 4.5, and 2.9 log10 CFU/ml, whereas
      those of strain ATCC 23745 were 4.1, > 4.5, and 1.2 log10 CFU/ml for each drug,
      respectively. These and other studies demonstrated that temafloxacin showed
      potential as an agent that could have been further developed for use in the
      treatment of anaerobic infections. However, the drug was removed from the market
      by its manufacturer because of toxicity issues. Although the release of newer
      fluoroquinolones that possess significant activity against anaerobic bacteria
      does not appear imminent, the time-kill studies performed in this study
      demonstrate that further research is warranted in the development of
      fluoroquinolones which possess significant antianaerobic activity.

PMID- 8285634
TI  - Experimental visceral leishmaniasis: role of trans-aconitic acid in combined
      chemotherapy.
AB  - We previously reported the effectiveness of trans-aconitic acid (TAA) as an
      antileishmanial compound. Inhibitory effects of TAA along with other
      antileishmanial compounds on transformation and in vitro multiplication in
      macrophage cultures of Leishmania donovani have been assessed. The efficacy of
      TAA in combined chemotherapy of experimental visceral leishmaniasis has also been
      evaluated along with those of commonly used antileishmanial compounds such as
      sodium stibogluconate, pentamidine, and allopurinol. TAA (2 mM) inhibited
      transformation of L. donovani amastigotes to promastigotes by 95.2%, whereas in
      combination with pentamidine (5 micrograms/ml), allopurinol (10 micrograms/ml),
      and sodium stibogluconate (50 micrograms of Sb per ml), it inhibited
      transformation by about 100, 99, and 98.5%, respectively. Sodium stibogluconate
      (20 micrograms of Sb per ml), pentamidine (2 micrograms/ml), and allopurinol (5
      micrograms/ml) suppressed the amastigote burden in peritoneal macrophage cultures
      from BALB/c mice by 32.6, 56.1, and 46.3%, respectively. When these three drugs
      were used along with TAA (5 mM), the parasite loads were reduced by 100, 100, and
      88.1%, respectively. TAA (5 mM) alone suppressed the amastigote burden by 59.5%.
      In experimental visceral leishmaniasis in hamsters (1-month model), TAA at a dose
      of 200 mg/kg of body weight per day suppressed the spleen parasite load by 73.5%,
      and TAA in combination with sodium stibogluconate (50 mg of Sb per kg per day),
      pentamidine (8 mg/kg/day), and allopurinol (15 mg/kg/day) inhibited the spleen
      parasite load by 98, 98.9, and 97%, respectively. Individually, these three drugs
      inhibited the parasite load by 35, 20, and 22%, respectively. TAA (400 mg/kg/day)
      inhibited the spleen parasite load by 99.8%, but an inhibitory effect of
      approximately 100% was noted when TAA was supplemented with an antileishmanial
      drug. TAA was administered in experimental animals through oral, intraperitoneal,
      and intramuscular routes; the intramuscular route was most effective.

PMID- 8285635
TI  - Fusidic acid alone or in combination with vancomycin for therapy of experimental
      endocarditis due to methicillin-resistant Staphylococcus aureus.
AB  - The usefulness of fusidic acid, alone or combined with vancomycin, was
      investigated for the therapy of experimental endocarditis caused in rabbits by a
      methicillin-resistant strain of Staphylococcus aureus. In vitro killing curves
      showed an indifferent interaction between the two antibiotics. In vivo,
      vancomycin alone was as effective as a vancomycin-fusidic acid combination (P <
      0.05 versus control animals). No resistance to fusidic acid emerged during
      combination therapy. Fusidic acid alone was not effective. Resistance emerged in
      5 of 12 animals treated with fusidic acid alone and was responsible for
      antibacterial failure. Fusidic acid alone was effective (P < 0.001) and did not
      select resistant strains if therapy was started when animals retained a smaller
      inoculum. We concluded that the vancomycin-fusidic acid combination exhibited no
      advantage over vancomycin alone in this model.

PMID- 8285636
TI  - Bactericidal activity of the fluoroquinolone WIN 57273 against high-level
      gentamicin-resistant Enterococcus faecalis.
AB  - The fluoroquinolone WIN 57273 showed identical bactericidal activities (MBC for
      90% of the strains = 0.25 micrograms/ml) for bacteremic strains of Enterococcus
      faecalis with and without high-level gentamicin resistance. WIN 57273 was
      bactericidal in time-kill measurements with highly gentamicin-resistant,
      ciprofloxacin-susceptible strains of E. faecalis. However, WIN 57273 was
      indifferent with penicillin for gentamicin-resistant E. faecalis and was not
      bactericidal for ciprofloxacin-resistant E. faecalis.

PMID- 8285637
TI  - Plasmid-associated hemolysin and aggregation substance production contribute to
      virulence in experimental enterococcal endocarditis.
AB  - A rabbit endocarditis model was utilized to evaluate the virulence conferred by
      the conjugative plasmid pAD1 with the following strains: Enterococcus faecalis
      plasmid-free FA2-2 and FA2-2 containing plasmids pAD1 (hemolysin and aggregation
      substance positive), pAM9058 (insertional inactivation of hemolysin), and pAM944
      or pAM947 (insertional inactivation of aggregation substance). All isolates were
      similar in ability to produce endocarditis. Mean vegetation weight was greater in
      animals inoculated with strains that produced aggregation substance (P < 0.01).
      Mortality was significantly increased in animals given FA2-2 containing pAD1
      compared with those given all other strains (P < 0.01). These results suggest
      that the combination of hemolysin and aggregation substance is associated with
      increased mortality and that vegetation weight is associated with production of
      aggregation substance in experimental E. faecalis endocarditis.

PMID- 8285638
TI  - Effects of phosphonylmethoxyalkyl derivatives studied with a murine model for
      abortion induced by equine herpesvirus 1.
AB  - (S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) and (S)-9-(3-hydroxy-2
      phosphonylmethoxypropyl)cytosine (HPMPC) were tested in a mouse model for equine
      herpesvirus 1-induced abortion. HPMPA, given twice daily, reduced virus
      replication, but the compound was embryotoxic. A single dose of HPMPC, however,
      reduced the incidence of abortion and transfer of virus to the fetuses while
      producing no obvious toxic effects.

PMID- 8285639
TI  - Selective repression of v-abl-encoded protein by N-methylisatin-beta-4',4'
      diethylthiosemicarbazone and N-allylisatin-beta-4',4'-diallylthiosemicarbazone.
AB  - N-Methylisatin-beta-4',4'-diethylthiosemicarbazone (M-IBDET) and N-allylisatin
      beta-4',4'-diallylthiosemicarbazone (A-IBDAT) selectively inhibited v-abl protein
      (P120), an oncogene product associated with tyrosine kinase activity.
      Concentrations of M-IBDET ranging between 0.17 and 0.64 microM and concentrations
      of A-IBDAT from 1.45 to 2.9 microM reduced tyrosine kinase activity
      significantly, whereas 0.64 microM M-IBDET and 2.9 microM A-IBDAT blocked P120
      production. Cellular growth rate, protein production, and synthesis of p45 actin
      and p53 nuclear oncogene were not affected at these conditions. M-IBDET and A
      IBDAT selectively suppress the v-abl oncogene as well as Moloney murine leukemia
      virus production.

PMID- 8285640
TI  - Reduced susceptibilities of Shigella sonnei strains isolated from patients with
      dysentery to fluoroquinolones.
AB  - Seven clinical isolates of Shigella sonnei with reduced susceptibilities to
      fluoroquinolones (sparfloxacin, ciprofloxacin, and ofloxacin) were obtained. The
      MICs of fluoroquinolones against these S. sonnei strains were 16 to 32 times
      higher than those obtained against typical strains that are highly susceptible to
      these agents. The kinetics of [14C]ofloxacin accumulation in these clinical
      strains were not different from those in the fully susceptible strains. However,
      DNA synthesis was much less inhibited by ofloxacin in the strains with reduced
      susceptibility. Analysis of the in vitro activity of the partially purified DNA
      gyrase from these isolates showed that the decreased quinolone susceptibility of
      the S. sonnei strains was likely due to mutation of the DNA gyrase subunit A
      gene.

PMID- 8285641
TI  - Ganciclovir prophylaxis decreases frequency and severity of cytomegalovirus
      disease in seropositive liver transplant recipients treated with OKT3 monoclonal
      antibodies.
AB  - The efficacy of ganciclovir, given prophylactically, to prevent cytomegalovirus
      related disease was evaluated in liver transplant recipients, mostly
      seropositive, under treatment with OKT3 monoclonal antibodies. The incidence of
      cytomegalovirus disease and visceral involvement was reduced, respectively, from
      52 and 36% in the control group to 12 and 8% in the ganciclovir-treated patients.
      Leukopenia was a frequent (32%) side effect of ganciclovir administration.

PMID- 8285642
TI  - Activities of potential therapeutic and prophylactic antibiotics against blood
      culture isolates of viridans group streptococci from neutropenic patients
      receiving ciprofloxacin.
AB  - All 47 sequential blood culture isolates of viridans group streptococci obtained
      from febrile neutropenic patients receiving quinolone prophylaxis were
      susceptible to vancomycin, teicoplanin, and imipenem. Resistance to
      benzylpenicillin (MIC for 50% of isolates [MIC50], 0.125 microgram/ml) and
      ceftazidime (MIC50, 4 micrograms/ml) was common. Most isolates were susceptible
      to amoxicillin, co-amoxiclav (amoxicillin-clavulanic acid at a 2:1 ratio by
      weight), azlocillin, clarithromycin, and erythromycin, with azithromycin showing
      comparable activity. The MIC90 of sparfloxacin was 1 microgram/ml; those for
      ciprofloxacin and ofloxacin were > 16 and 16 micrograms/ml, respectively.

PMID- 8285643
TI  - Use of human renal proximal tubule cell cultures for studying foscarnet-induced
      nephrotoxicity in vitro.
AB  - Foscarnet is an antiviral agent used for the treatment of cytomegalovirus
      retinitis and acyclovir-resistant herpes simplex virus infections in AIDS
      patients. Renal impairment has been reported for many patients treated with
      foscarnet. We have studied the effects of foscarnet on the viability (estimated
      by neutral red inclusion) and ultrastructure of cultures of human renal proximal
      tubule cells (HRPTC) isolated from the kidneys of five cadavers and cultured. The
      degree of foscarnet-induced toxicity was dose dependent and varied among the
      HRPTC cultures. The data obtained by using the in vitro system of HRPTC mimic the
      data of the clinical trials in that there is a dose-dependent individual
      variation among human cases in response to foscarnet treatment. Thus, these
      cultures are extremely well-suited to investigations of the mechanism of toxicity
      at the subcellular level.

PMID- 8285644
TI  - In vitro antibiotic susceptibility testing of different strains of Mycoplasma
      fermentans isolated from a variety of sources.
AB  - The in vitro susceptibilities to antibiotics of 24 strains of Mycoplasma
      fermentans (isolated from human immunodeficiency virus type 1-infected AIDS
      patients, non-AIDS patients with acute respiratory disease, and tissue culture)
      were determined. MICs for 90% of the strains tested (micrograms per milliliter)
      were obtained for chloramphenicol (1.25), ciprofloxacin (0.078), clindamycin
      (0.078), doxycycline (0.625), erythromycin (> 10), gentamicin (> 10),
      levofloxacin (0.078), lincomycin (0.156), streptomycin (> 10), and tetracycline
      (0.625).

PMID- 8285645
TI  - In vitro activities of antimicrobial agents against clinical isolates of
      Flavimonas oryzihabitans obtained from patients with cancer.
AB  - We evaluated the in vitro activities of 21 different antimicrobial agents against
      nine clinical isolates of Flavimonas oryzihabitans obtained from patients with
      cancer. The organisms were susceptible to most agents commonly used for the
      empiric therapy (aminoglycosides, ureidopenicillins, extended-spectrum
      cephalosporins, monobactams, and carbapenems) and prevention of infections
      (quinolones and trimethoprim-sulfamethoxazole) in this patient population.

PMID- 8285646
TI  - Increased susceptibility of Pseudomonas aeruginosa to ciprofloxacin in the
      presence of vancomycin.
AB  - Vancomycin in combination with ciprofloxacin exhibited synergy against 7 of 10
      strains of Pseudomonas aeruginosa. MICs for the microbial strains used in this
      study ranged from 0.0325 to 3.0 micrograms/ml for ciprofloxacin and from 23.5 to
      > 188 micrograms/ml for vancomycin. Combinations of these antibiotics, tested in
      a checkerboard pattern, gave fractional inhibitory concentrations of 0.5 or less
      for 7 of the 10 strains tested.

PMID- 8285647
TI  - In vitro activity of Bay Y3118 against anaerobic bacteria.
AB  - The antimicrobial activity of a new quinolone, Bay Y3118, was determined against
      326 strains of anaerobic bacteria and compared with the activities of ampicillin
      sulbactam, cefotetan, clindamycin, imipenem, metronidazole, and sparfloxacin. The
      National Committee for Clinical Laboratory Standards-approved Wadsworth agar
      dilution technique with Brucella-laked blood agar was used throughout the study.
      Breakpoints used to determine the percent susceptible were 2 micrograms/ml for
      Bay Y3118 and sparfloxacin, 4 micrograms/ml for clindamycin, 8 micrograms/ml for
      imipenem, 16 micrograms/ml for metronidazole and ampicillin-sulbactam, and 32
      micrograms/ml for cefotetan. Species tested included Bacteroides fragilis (57
      strains), other B. fragilis group species (79 strains), Bacteroides gracilis (10
      strains), other Bacteroides spp. (9 strains), Prevotella spp. (30 strains),
      Porphyromonas spp. (9 strains), Fusobacterium spp. (36 strains), Bilophila
      wadsworthia (14 strains), Clostridium spp. (36 strains), Peptostreptococcus spp.
      (20 strains), and gram-positive non-spore-forming rods (26 strains). Bay Y3118
      inhibited all but 1 of 326 anaerobic bacteria tested at the breakpoint level or
      lower.

PMID- 8285648
TI  - Antimicrobial susceptibilities of Nocardia spp.

PMID- 8285649
TI  - Effects on food cravings of a very low calorie diet or a balanced, low calorie
      diet.
AB  - It is commonly believed that dieting and the restriction of specific types of
      foods produces cravings for these foods. This study, therefore, compared changes
      in self-reported cravings experienced by 93 obese subjects with Type II diabetes
      who were randomly assigned to behavioral treatment programmes which used either:
      (a) a balanced, low-calorie diet (LCD) of 1000-1200 kcal/day throughout, with all
      foods allowed in moderation, or (b) a programme which included a 12-week period
      of a very low calorie diet (VLCD), where intake was restricted to 400 kcal/day
      with only lean meat, fish, or fowl allowed. There were significant decreases in
      cravings for all types of foods over the 20 weeks of the study for both the VLCD
      and the LCD conditions. The decreases in cravings were particularly pronounced
      for the VLCD condition for low-fat, high-protein foods (the only foods allowed on
      the VLCD) and for complex carbohydrates, especially grains (one of the types of
      foods prohibited on this diet). There was no evidence to support the belief that
      restricting intake of certain foods leads to increased craving for these foods or
      that the magnitude of weight loss is related to food cravings.

PMID- 8285650
TI  - No effect of extended home use on linking for sensory characteristics of reduced
      fat foods.
AB  - In order to assess whether and to what extent extended sensory exposure would
      modify liking for the sensory characteristics of specific reduced-fat food items,
      consumers were provided with unlabelled full- or reduced-fat (FF or RF) versions
      of two foods for home use over 12 weeks. Group 1 (n = 30) received unlabelled RF
      cheddar cheese and FF potato crisps, and group 2 (n = 26) received the
      alternative versions of these same products. Blind sensory tests on these plus a
      control item (savoury crackers) were carried out at weeks 0, 3, 6, 9, and 12. A
      control group (n = 23) participated only in sensory tests. The two versions of
      crisps did not substantially differ initially, and showed minimal changes in
      ratings over time. The cheeses differed more substantially in sensory quality,
      and there were a number of significant changes in pleasantness ratings and
      selected attribute ratings over time. However, these were largely similar for all
      groups and therefore not specifically related to the use of the specific
      products. Group 1 consumed less cheese than group 2, but consumption did not
      change over time. These data indicate that extended home use did not have any
      unique facilitating effect on sensory or hedonic responses to these RF foods and
      suggest that, in the absence of specific cognitive cues or an overall change in
      the sensory or nutritional composition of the diet, consumers do not exhibit any
      spontaneous change in liking for the sensory characteristics of RF versions of
      foods.

PMID- 8285651
TI  - Bite size, ingestion rate, and meal size in lean and obese women.
AB  - The effect of bite size on ingestion rate, satiation, and meal size was studied
      in nine lean and nine obese women. On separate days, subjects were given one of
      three bite sizes of sandwiches and one of two bite sizes of bagels with cream
      cheese to eat in a laboratory lunch. Decreasing bite size significantly lowered
      ingestion rate for the whole meal. The effect was most pronounced at the
      beginning of meals. As bite size decreased from 15 to 5 g, the average ingestion
      rate decreased from (mean +/- SEM) 19.4 +/- 2.0 to 15.9 +/- 2.0 g/min (p <
      0.001). The initial ingestion rate decreased from 30.0 +/- 2.9 to 19.6 +/- 1.7
      g/min (p < 0.001). The larger the bite size, the more quickly ingestion rate
      decelerated; by the end of meals, ingestion rate was not different across
      conditions. The decrease in ingestion rate with smaller bites was offset by an
      increase in meal duration, such that meal size did not differ across conditions.
      Eating behavior of lean and obese subjects was not different. There were
      individual differences related to ingestion rate, but these were not related to
      body weight nor to meal size. These results bring into question the
      recommendation of behavior therapists that obese people eat more slowly in order
      to eat less.

PMID- 8285652
TI  - Food and society.

PMID- 8285653
TI  - Towards a concept of food-related life style.

PMID- 8285654
TI  - The validity of appetite ratings.

PMID- 8285655
TI  - Serotonergic mechanisms and ingestion: pharmacological facts and physiological
      promises.

PMID- 8285656
TI  - Persistence of sham feeding after real-fed gastric loads in rats.
AB  - Esophagostomized rats were permitted to "real-feed" a glucose solution
      (Experiment 1) or milk (Experiment 2), by receiving intragastric (IG) infusions
      concurrent with sham feeding. This was done for the first part of the feeding
      session; then the IG infusions were discontinued so that subsequent ingestion was
      sham. When such infusions stopped after 80% of real-meal volume had been
      delivered, they had no measurable effect on subsequent oral ingestion: sham
      feeding persisted as if nothing had been delivered IG. Therefore, the onset of
      postingestive satiety, at least in experienced sham-feeding rats, is all-or-none
      or close to it: if the IG loads are even slightly short of what is required to
      abolish sham feeding, then they do not affect sham feeding at all. This is so
      even if the postingestive events occur within their normal behavioral context.

PMID- 8285657
TI  - Is cholecystokinin a satiety hormone? Correlations of plasma cholecystokinin with
      hunger, satiety and gastric emptying in normal volunteers.
AB  - This study was designed to test the putative role of plasma cholecystokinin (CCK)
      in eating behaviour by examining the relationships between bioassayed plasma CCK
      concentrations and rated sensations of satiety and hunger following the ingestion
      of an appetizing nutrient-dense meal and between plasma profiles of CCK and
      scintigraphically determined gastric emptying in nine healthy male volunteers.
      Mean plasma CCK levels from the whole group showed a significant negative
      correlation with mean hunger ratings (r = -0.64) and a positive correlation with
      fullness (r = +0.68). However, there was considerable interindividual variation
      and negative correlations with hunger were only seen in three out of nine
      subjects and positive correlations with fullness in four out of nine subjects. In
      contrast, there was a strong relationship between the plasma CCK produced over
      the first 2 h after the meal and the half time for gastric emptying of the meal
      (r = -0.81). These data do not support a direct role for circulating levels of
      CCK in the control of hunger and satiety following a meal. Instead, the strong
      correlation with gastric emptying is compatible with release of CCK in response
      to nutrient delivery into the small intestine.

PMID- 8285658
TI  - Direct plating procedure for enumerating Vibrio vulnificus in oysters
      (Crassostrea virginica).
AB  - A procedure for enumerating and identifying Vibrio vulnificus in oysters was
      developed and evaluated. This method consists of growth on a direct plating
      medium (VVE medium) for isolating the organism from shellfish tissues, followed
      by biochemical tests for differentiating and identifying presumptively positive
      isolates. Densities of V. vulnificus are reliably obtained in 2 to 4 days, and as
      few as 10 culturable cells per 100 g can be identified. The procedure was
      evaluated by using a DNA probe technique specific for the cytotoxin-hemolysin
      gene of V. vulnificus and gas chromatographic analysis of the fatty acid contents
      of positive isolates. Only 3.2 and 0.4% of the isolates gave false-positive and
      false-negative results, respectively. The average level of recovery on VVE medium
      for 33 strains, including both clinical and environmental isolates, was 92% of
      the level of recovery obtained with brain heart infusion agar supplemented with
      1% NaCl. The densities of V. vulnificus in oyster homogenates and individual
      oysters harvested from gulf and Atlantic coastal waters revealed that seasonally
      high levels occurred. The VVE medium procedure facilitated enumeration of this
      pathogen in molluscan shellfish and had a distinct advantage over the widely used
      most-probable-number procedure for V. vulnificus enumeration, which requires 5 to
      7 days and often gives improbable and imprecise results.

PMID- 8285659
TI  - A comparison of NO and N2O production by the autotrophic nitrifier Nitrosomonas
      europaea and the heterotrophic nitrifier Alcaligenes faecalis.
AB  - Soil microorganisms are important sources of the nitrogen trace gases NO and N2O
      for the atmosphere. Present evidence suggests that autotrophic nitrifiers such as
      Nitrosomonas europaea are the primary producers of NO and N2O in aerobic soils,
      whereas denitrifiers such as Pseudomonas spp. or Alcaligenes spp. are responsible
      for most of the NO and N2O emissions from anaerobic soils. It has been shown that
      Alcaligenes faecalis, a bacterium common in both soil and water, is capable of
      concomitant heterotrophic nitrification and denitrification. This study was
      undertaken to determine whether heterotrophic nitrification might be as important
      a source of NO and N2O as autotrophic nitrification. We compared the responses of
      N. europaea and A. faecalis to changes in partial O2 pressure (pO2) and to the
      presence of typical nitrification inhibitors. Maximal production of NO and N2O
      occurred at low pO2 values in cultures of both N. europaea (pO2, 0.3 kPa) and A.
      faecalis (pO2, 2 to 4 kPa). With N. europaea most of the NH4+ oxidized was
      converted to NO2-, with NO and N2O accounting for 2.6 and 1% of the end product,
      respectively. With A. faecalis maximal production of NO occurred at a pO2 of 2
      kPa, and maximal production of N2O occurred at a pO2 of 4 kPa. At these low pO2
      values there was net nitrite consumption. Aerobically, A. faecalis produced
      approximately the same amount of NO but 10-fold more N2O per cell than N.
      europaea did. Typical nitrification inhibitors were far less effective for
      reducing emissions of NO and N2O by A. faecalis than for reducing emissions of NO
      and N2O by N. europaea.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285660
TI  - New medium for the simultaneous detection of total coliforms and Escherichia coli
      in water.
AB  - A new membrane filter agar medium (MI agar) containing a chromogen, indoxyl-beta
      D-glucuronide, and a fluorogen, 4-methylumbelliferyl-beta-D-galactopyranoside,
      was developed to simultaneously detect and enumerate Escherichia coli and total
      coliforms (TC) in water samples on the basis of their enzyme activities. TC
      produced beta-galactosidase, which cleaved 4-methylumbelliferyl-beta-D
      galactopyranoside to form 4-methylumbelliferone, a compound that fluoresced under
      longwave UV light (366 nm), while E. coli produced beta-glucuronidase, which
      cleaved indoxyl-beta-D-glucuronide to form a blue color. The new medium TC and E.
      coli recoveries were compared with those of mEndo agar and two E. coli media,
      mTEC agar and nutrient agar supplemented with 4-methylumbelliferyl-beta-D
      glucuronide, using natural water samples and spiked drinking water samples. On
      average, the new medium recovered 1.8 times as many TC as mEndo agar, with
      greatly reduced background counts (< or = 7%). These differences were
      statistically significant (significance level, 0.05). Although the overall
      analysis revealed no statistically significant difference between the E. coli
      recoveries on MI agar and mTEC agar, the new medium recovered more E. coli in 16
      of 23 samples (69.6%). Both MI agar and mTEC agar recovered significantly more E.
      coli than nutrient agar supplemented with 4-methylumbelliferyl-beta-D
      glucuronide. Specificities for E. coli, TC, and noncoliforms on MI agar were
      95.7% (66 of 69 samples), 93.1% (161 of 173 samples), and 93.8% (61 of 65
      samples), respectively. The E. coli false-positive and false-negative rates were
      both 4.3%. This selective and specific medium, which employs familiar membrane
      filter technology [corrected] to analyze several types of water samples, is less
      expensive than the liquid chromogen and fluorogen media and may be useful for
      compliance monitoring of drinking water.

PMID- 8285661
TI  - Survival of subsurface microorganisms exposed to UV radiation and hydrogen
      peroxide.
AB  - Aerobic and microaerophilic subsurface bacteria were screened for resistance to
      UV light. Contrary to the hypothesis that subsurface bacteria should be sensitive
      to UV light, the organisms studied exhibited resistance levels as efficient as
      those of surface bacteria. A total of 31% of the aerobic subsurface isolates were
      UV resistant, compared with 26% of the surface soil bacteria that were tested.
      Several aerobic, gram-positive, pigmented, subsurface isolates exhibited greater
      resistance to UV light than all of the reference bacterial strains tested except
      Deinococcus radiodurans. None of the microaerophilic, gram-negative,
      nonpigmented, subsurface isolates were UV resistant; however, these isolates
      exhibited levels of sensitivity similar to those of the gram-negative reference
      bacteria Escherichia coli B and Pseudomonas fluorescens. Photoreactivation
      activity was detected in three subsurface isolates, and strain UV3 exhibited a
      more efficient mechanism than E. coli B. The peroxide resistance of four
      subsurface isolates was also examined. The aerobic subsurface bacteria resistant
      to UV light tolerated higher levels of H2O2 than the microaerophilic organisms.
      The conservation of DNA repair pathways in subsurface microorganisms may be
      important in maintaining DNA integrity and in protecting the organisms against
      chemical insults, such as oxygen radicals, during periods of slow growth.

PMID- 8285662
TI  - Bacterial strains from human feces that reduce CO2 to acetic acid.
AB  - We used dilutions of fecal suspensions from a human volunteer to enrich cultures
      for bacteria that reduce CO2 to acetate in the colon. The soluble enrichment
      substrates used were glucose, methanol, formate, and vanillate, which were used
      with a gas phase that contained 80% N2 and 20% CO2. The gaseous enrichment
      substrates used were 80% H2-20% CO2 and 50% CO-50% CO2. We isolated three
      different strains that produced acetate from CO2. One strain produced acetate
      from methanol, vanillate, H2-CO2, glucose, and other sugars. The other two
      strains did not form acetate from methanol or vanillate. Both of the latter
      strains formed acetate from glucose and other sugars, but only one of these
      strains formed acetate from H2-CO2. Both of these strains cometabolized formate.
      However, none of the enrichment cultures or pure cultures used CO or formate as a
      substrate for growth. The two strains that produced acetate from H2 and CO2 grew
      slowly when the gases alone were used as substrates, but they rapidly
      cometabolized H2 and CO2 when they were grown with organic substrates. The
      ability of all of the strains to produce acetate from CO2 and/or other one-carbon
      precursors was verified by determining the radioactivity of the methyl and
      carboxyl groups of the acetate formed after growth with 14CO2 or other
      radioactively labeled one-carbon precursors.

PMID- 8285663
TI  - Utilization of xylooligosaccharides by selected ruminal bacteria.
AB  - The ability of ruminal bacteria to utilize xylooligosaccharides was examined.
      Xylooligosaccharides were prepared by partially hydrolyzing oat spelt xylan in
      phosphoric acid. This substrate solution was added (0.2%, wt/vol) to a complex
      medium containing yeast extract and Trypticase that was inoculated with
      individual species of ruminal bacteria, and growth and utilization were monitored
      over time. All of the xylanolytic bacteria examined were able to utilize this
      oligosaccharide mixture as a growth substrate. Butyrivibrio fibrisolvens,
      Eubacterium ruminantium, and Ruminococcus albus used xylooligosaccharides and
      whole, unhydrolyzed xylan to similar extents, while Prevotella ruminicola used
      twice as much xylooligosaccharides as xylan (76 versus 34%). Strains of
      Selenomonas ruminantium were the only nonxylanolytic species that were able to
      grow on xylooligosaccharides. The ability of individual S. ruminantium strains to
      utilize xylooligosaccharides was correlated with the presence of xylosidase and
      arabinosidases activities.

PMID- 8285664
TI  - Cloning and characterization of a cDNA from Aspergillus parasiticus encoding an O
      methyltransferase involved in aflatoxin biosynthesis.
AB  - Aflatoxins are polyketide-derived secondary metabolites produced by the fungi
      Aspergillus flavus and Aspergillus parasiticus. Among the catalytic steps in the
      aflatoxin biosynthetic pathway, the conversion of sterigmatocystin to O
      methylsterigmatocystin and the conversion of dihydrosterigmatocystin to dihydro-O
      methylsterigmatocystin are catalyzed by an S-adenosylmethionine-dependent O
      methyltransferase. A cDNA library was constructed by using RNA isolated from a 24
      h-old culture of wild-type A. parasiticus SRRC 143 and was screened by using
      polyclonal antiserum raised against a purified 40-kDa O-methyltransferase
      protein. A clone that harbored a full-length cDNA insert (1,460 bp) containing
      the 1,254-bp coding region of the gene omt-1 was identified by the antiserum and
      isolated. The complete cDNA sequence was determined, and the corresponding 418
      amino-acid sequence of the native enzyme with a molecular weight of 46,000 was
      deduced. This 46-kDa native enzyme has a leader sequence of 41 amino acids, and
      the mature form of the enzyme apparently consists of 377 amino acids and has a
      molecular weight of 42,000. Direct sequencing of the purified mature enzyme from
      A. parasiticus SRRC 163 showed that 19 of 22 amino acid residues were identical
      to the amino acid residues in an internal region of the deduced amino acid
      sequence of the mature protein. The 1,460-bp omt-1 cDNA was cloned into an
      Escherichia coli expression system; a Western blot (immunoblot) analysis of crude
      extracts from this expression system revealed a 51-kDa fusion protein (fused with
      a 5-kDa beta-galactosidase N-terminal fragment).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285665
TI  - Reduction of uranium by cytochrome c3 of Desulfovibrio vulgaris.
AB  - The mechanism for U(VI) reduction by Desulfovibrio vulgaris (Hildenborough) was
      investigated. The H2-dependent U(VI) reductase activity in the soluble fraction
      of the cells was lost when the soluble fraction was passed over a cationic
      exchange column which extracted cytochrome c3. Addition of cytochrome c3 back to
      the soluble fraction that had been passed over the cationic exchange column
      restored the U(VI)-reducing capacity. Reduced cytochrome c3 was oxidized by
      U(VI), as was a c-type cytochrome(s) in whole-cell suspensions. When cytochrome
      c3 was combined with hydrogenase, its physiological electron donor, U(VI) was
      reduced in the presence of H2. Hydrogenase alone could not reduce U(VI). Rapid
      U(VI) reduction was followed by a subsequent slow precipitation of the U(IV)
      mineral uraninite. Cytochrome c3 reduced U(VI) in a uranium-contaminated surface
      water and groundwater. Cytochrome c3 provides the first enzyme model for the
      reduction and biomineralization of uranium in sedimentary environments.
      Furthermore, the finding that cytochrome c3 can catalyze the reductive
      precipitation of uranium may aid in the development of fixed-enzyme reactors
      and/or organisms with enhanced U(VI)-reducing capacity for the bioremediation of
      uranium-contaminated waters and waste streams.

PMID- 8285666
TI  - Pediocin PA-1, a bacteriocin from Pediococcus acidilactici PAC1.0, forms
      hydrophilic pores in the cytoplasmic membrane of target cells.
AB  - Pediocin PA-1 is a bacteriocin which is produced by Pediococcus acidilactici
      PAC1.0. We demonstrate that pediocin PA-1 kills sensitive Pediococcus cells and
      acts on the cytoplasmic membrane. In contrast to its lack of impact on immune
      cells, pediocin PA-1 dissipates the transmembrane electrical potential and
      inhibits amino acid transport in sensitive cells. Pediocin interferes with the
      uptake of amino acids by cytoplasmic membrane vesicles derived from sensitive
      cells, while it is less effective with membranes derived from immune cells. In
      liposomes fused with membrane vesicles derived from both sensitive and immune
      cells, pediocin PA-1 elicits an efflux of small ions and, at higher
      concentrations, an efflux of molecules having molecular weights of up to 9,400.
      Our data suggest that pediocin PA-1 functions in a voltage-independent manner but
      requires a specific protein in the target membrane.

PMID- 8285667
TI  - Pulmonary clearance and inflammatory response in C3H/HeJ mice after intranasal
      exposure to Pseudomonas spp.
AB  - The environmental release of engineered microorganisms has caused health and
      environmental concerns. In this study, an animal model was used to examine health
      effects following pulmonary exposure to environmental and clinical isolates. In
      order to rule out the possibility that an adverse response was caused by
      endotoxin, 50% lethal doses (LD50) were determined, when possible, with endotoxin
      sensitive (C3HeB/FeJ) and endotoxin-resistant (C3H/HeJ) mice by using both
      environmental isolates (Pseudomonas aeruginosa BC16, BC17, BC18, and AC869 and
      Pseudomonas maltophilia BC6) and clinical isolates (P. aeruginosa PAO1 and DG1).
      The LD50 of strains AC869, DG1, and PAO1 are 1.05 x 10(7), 6.56 x 10(6), and 1.02
      x 10(7) CFU, respectively, in C3HeB/FeJ mice and 1.05 x 10(7), 1.00 x 10(7), and
      2.75 x 10(6) CFU, respectively, in C3H/HeJ mice. Strains BC17 and BC18 were not
      lethal to the animals. On the basis of the LD50 data, an appropriate sublethal
      dose (approximately 10(6) CFU) was selected. Animals were challenged intranasally
      with microorganisms, and clearance from the lungs and nasal cavity was
      determined. Strains BC17, BC18, and AC869 were not detected in lungs or nasal
      washes 14 days following treatment. Strains BC6, BC16, and DG1 were recovered
      from the nasal cavities at the end of the experiment. Only strain PAO1 was
      detected in lungs and in nasal cavities 14 days after treatment. At selected
      intervals following treatment, the percentages of polymorphonuclear leukocytes
      and lymphocytes in bronchoalveolar lavage samples were determined. P. aeruginosa
      AC869, PAO1, and DG1 elicited a relatively strong inflammatory response which was
      indirectly related to lung clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285668
TI  - Reductive dehalogenation of the trichloromethyl group of nitrapyrin by the
      ammonia-oxidizing bacterium Nitrosomonas europaea.
AB  - Suspensions of Nitrosomonas europaea catalyzed the reductive dehalogenation of
      the commercial nitrification inhibitor nitrapyrin (2-chloro-6
      trichloromethylpyridine). The product of the reaction was identified as 2-chloro
      6-dichloromethylpyridine by its mass fragmentation and nuclear magnetic resonance
      spectra. A small amount of 2-chloro-6-dichloromethylpyridine accumulated during
      the conversion of nitrapyrin to 6-chloropicolinic acid in an aerated solution in
      the presence of ammonia (T. Vannelli and A.B. Hooper, Appl. Environ. Microbiol.
      58:2321-2325, 1992). Nearly stoichiometric conversion of nitrapyrin to 2-chloro-6
      dichloromethylpyridine occurred at very low oxygen concentrations and in the
      presence of hydrazine as a source of electrons. Under these conditions the
      turnover rate was 0.37 nmol of nitrapyrin per min per mg of protein. Two specific
      inhibitors of ammonia oxidation, acetylene and allylthiourea, inhibited the rate
      of the dehalogenation reaction by 80 and 84%, respectively. In the presence of
      D2O, all 2-chloro-6-dichloromethylpyridine produced in the reaction was
      deuterated at the methyl position. In an oxygenated solution and in the presence
      of ammonia or hydrazine, cells did not catalyze the oxidation of exogenously
      added 2-chloro-6-dichloromethylpyridine to 6-chloropicolinic acid. Thus, 2-chloro
      6-dichloromethylpyridine is apparently not an intermediate in the aerobic
      production of 6-chloropicolinic acid from nitrapyrin.

PMID- 8285669
TI  - Detection of Legionella species in sewage and ocean water by polymerase chain
      reaction, direct fluorescent-antibody, and plate culture methods.
AB  - Legionella spp. are ubiquitous in most environmental water sources; however,
      sewage treatment plants have not been examined as potential environmental
      reservoirs for these bacteria. This study used polymerase chain reaction, direct
      fluorescent-antibody staining, and culture methods to examine raw and treated
      sewage, ocean-receiving waters, and nearshore coastal environments for the
      presence of Legionella pneumophila and other Legionella spp. The study concluded
      that Legionella spp. are present in all phases of sewage treatment and that
      population numbers do not significantly decline through the treatment process.
      Ocean-receiving waters located 5 miles offshore, where the treated sewage is
      discharged, were found to contain Legionella spp., but ocean water between the
      discharge site and coastal bathing beaches was negative. This suggests that the
      Legionella spp. from the ocean discharge site were not reaching the nearshore
      beach waters. A flood control channel and river that entered the ocean were found
      to contain Legionella spp., and a nearby beach swimming area was also found to be
      positive, suggesting that land runoff from the flood control channel and river
      were the source of the Legionella spp. in the beach water samples that tested
      positive.

PMID- 8285670
TI  - Cloning and expression of the transposable chlorobenzoate-3,4-dioxygenase genes
      of Alcaligenes sp. strain BR60.
AB  - Growth on 3-chlorobenzoate was found to induce the enzymes of the protocatechuate
      meta ring fission pathway in Alcaligenes sp. strain BR60. The chlorobenzoate
      catabolic genes, designated cba, were localized to a 3.7-kb NotI-EcoRI fragment
      within the nonrepeated region of the composite transposon Tn5271. The cba genes
      were cloned onto two broad-host-range vectors and expressed in Escherichia coli
      and Alcaligenes sp. strain BR6024. In E. coli, expression of the cba genes with
      the IPTG (isopropyl-beta-D-thiogalactopyranoside)-inducible tac promoter of the
      IncQ vector pMMB66HE resulted in the production of protocatechuate and
      chlorodihydroxybenzoate metabolites of 3-chlorobenzoate. Expression of this
      construct in one orientation resulted in the formation of two polypeptides 51 and
      42 kDa in size. This result was confirmed by subcloning into pGEM3Zf and then
      incorporating L-35S-methionine into newly synthesized proteins, using the
      thermally regulated T7 polymerase-promoter system. Introduction of the NotI-EcoRI
      fragment into Alcaligenes sp. strain BR6024 (Cba-P), using the IncP broad-host
      range, mobilizable plasmid pBW13, restored the 3-chlorobenzoate-degradative
      phenotype and resulted in the accumulation of protocatechuate and
      chlorodihydroxybenzoate intermediates. The data indicate that a two-component
      dioxygenase specified by Tn5271 oxidizes 3-chlorobenzoate at the 3,4- or 4,5
      positions. This activity extends the range of pathways for chloroaromatic
      compounds known to be functional in the environment. The new pathway avoids the
      toxicity attributed to the accumulation of chlorocatechol metabolites in bacteria
      degrading chlorobenzoates.

PMID- 8285671
TI  - Diversity of cell envelope proteinase specificity among strains of Lactococcus
      lactis and its relationship to charge characteristics of the substrate-binding
      region.
AB  - The biochemical and genetical diversity of the subtilisin-like cell envelope
      proteinase (CEP) among Lactococcus lactis strains was investigated. The
      specificities of the proteinases of 16 strains toward the important cheese
      peptide alpha s1-casein fragment 1 to 23 and toward two differently charged
      chromophoric peptides have been determined. On the basis of the results, these
      strains could be classified into seven groups. The contribution to the
      specificity of specific residues in the large C-terminal segment, which
      differentiates this proteinase from most other members of the subtilisin family,
      was established with hybrid proteinases, even in the case of the small
      substrates. These remote residues and the subtilisin-like substrate-binding
      region are therefore assumed to be spatially close to each other and together
      constitute most of the binding region of CEP. DNA sequence analysis of fragments
      of the gene (prtP) encoding segments of the proteinase which contain the relevant
      residues of the substrate-binding region shows that among the strains studied,
      this binding region is the most negatively charged in the CEP group represented
      by strain HP and the positively charged in the CEP group represented by strains
      AM1 and SK11. Consequently, these two proteinase groups show the most divergent
      specificities. Each of the proteinases of the other groups shows a different
      intermediate specificity which in part is the reflection of an intermediate
      charge in the binding region. However, the results suggest that amino acid
      residues outside the segments known to be part of the CEP-binding region also
      contribute to specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285672
TI  - Purification and characterization of two 1,4-beta-xylan endohydrolases from the
      rumen fungus Neocallimastix frontalis.
AB  - Two beta-endoxylanases produced by Neocallimastix frontalis have been purified by
      ammonium sulfate precipitation, gel filtration, and ion-exchange chromatography.
      Xylanase I is a nonglycosylated protein with an apparent molecular mass of 45
      kDa. Xylanase II is a glycoprotein with an apparent molecular mass of 70 kDa. The
      pH optima of these enzymes were 5.5 and 6, respectively, and the temperature
      optimum was 55 degrees C for each enzyme. The endo mode of action of the enzymes
      was revealed by thin-layer chromatography of xylan hydrolysates. Antibodies
      raised against each purified protein exhibited no cross-reaction, confirming the
      biochemical specificities of the enzymes. Both enzymes exhibited carboxymethyl
      cellulase activity, and xylanase I was absorbed on crystalline cellulose,
      indicating that these enzymes might belong to the F family of beta-1,4
      glycanases.

PMID- 8285673
TI  - Dose response of Cryptosporidium parvum in outbred neonatal CD-1 mice.
AB  - Cryptosporidium parvum infectivity in a neonatal CD-1 mouse model was used to
      determine the dose needed to infect 50% of the population. The 50% infective dose
      was estimated to be 79 oocysts. It was observed that a mean oral inoculum of 23
      oocysts produced infection in 2 of 25 neonatal mice 7 days postinoculation. All
      animals became infected when the mean oral dose exceeded 310 oocysts per animal.
      The dose response of C. parvum was modeled with a logit dose-response model
      suitable for use in water disinfection studies.

PMID- 8285674
TI  - Molecular cloning and expression of two alpha-amylase genes from Streptococcus
      bovis 148 in Escherichia coli.
AB  - The alpha-amylase genes of Streptococcus bovis 148 were cloned in Escherichia
      coli MC1061, using pBR322. The recombinant plasmids were classified into two
      groups on the basis of their restriction maps. Southern blot analysis did not
      show homology between the two types of alpha-amylase genes, and the two alpha
      amylase genes existed on the chromosomal DNA of S. bovis 148. The enzymatic
      properties and N-terminal amino acid sequences of the two purified enzymes
      produced by the cloned E. coli strains were quite different from each other.
      Particularly, one alpha-amylase (Amy I) was adsorbed on raw corn starch and
      hydrolyzed raw corn starch, and another (Amy II) was not adsorbed on raw corn
      starch and did not hydrolyze raw corn starch. Amy I was considered to be the same
      as the extracellular alpha-amylase of S. bovis 148 in raw starch absorbability,
      ability to hydrolyze raw corn starch, enzymatic characteristics, N-terminal amino
      acid sequence, and mode of action on soluble starch. Amy II showed a unique
      pattern of oligosaccharide production from soluble starch compared with the
      extracellular alpha-amylase of S. bovis 148. Amy II was suggested to be an
      intracellular alpha-amylase of S. bovis 148.

PMID- 8285675
TI  - Comparison of Giardia lamblia and Giardia muris cyst inactivation by ozone.
AB  - Inactivation of Giardia lamblia and Giardia muris cysts was compared by using an
      ozone demand-free 0.05 M phosphate buffer in bench-scale batch reactors at 22
      degrees C. Ozone was added to each trial from a concentrated stock solution for
      contact times of 2 and 5 min. The viability of the control and treated cysts was
      evaluated by using the C3H/HeN mouse and Mongolian gerbil models for G. muris and
      G. lamblia, respectively. The resistance of G. lamblia to ozone was not
      significantly different from that of G. muris under the study conditions,
      contrary to previously reported data that suggested G. lamblia was significantly
      more sensitive to ozone than G. muris was. The simple Ct value for 2 log unit
      inactivation of G. lamblia was 2.4 times higher than the Ct value recommended by
      the Surface Water Treatment Rule.

PMID- 8285676
TI  - A simple, sensitive, and rapid method for detecting seed contaminated with highly
      virulent Leptosphaeria maculans.
AB  - A primer-directed DNA amplification polymerase chain reaction assay for detection
      of seed contaminated with highly virulent Leptosphaeria maculans was developed.
      The primers were derived from a 5,238-bp repetitive sequence present only in the
      highly virulent isolates of the fungus. A procedure for isolating DNA from
      organisms infesting germinating seed was also developed. Seeds were added to
      liquid fungal minimal medium, and the culture was incubated for 3 days at room
      temperature with shaking. The organisms were collected from the cultures by
      centrifugation and lysed with a combination of sodium dodecyl sulfate and
      proteinase K. The DNA was extracted with organic solvents and with a high-salt
      cetyltrimethylammonium bromide solution. It was also precipitated with a low-salt
      cetyltrimethylammonium bromide solution. The extensive treatments used for
      minimizing polysaccharide contamination greatly improved the reliability of the
      assay. The minimum contamination level (2 of 1,000 seeds) that was tested was
      successfully detected with this DNA isolation procedure. The reliability of the
      assay was 96% at the 1 to 2% level of seed contamination. The described method is
      less laborious and requires only 4 to 5 days for completion in comparison to the
      11 to 22 days required for the currently employed methods. In addition, large
      sample sizes can be easily handled, thus reducing the probability of contaminated
      seed escaping detection.

PMID- 8285677
TI  - In situ growth and activity and modes of penetration of Escherichia coli in
      unconsolidated porous materials.
AB  - Statistically reliable data on the in situ rates of growth, substrate
      consumption, and product formation are required to test the validity of the
      mathematical models developed for microbially enhanced oil recovery and in situ
      bioremediation processes. A simple, replicable porous-core system that could be
      aseptically divided into sections at various times was developed to follow the
      kinetics of microbial growth and metabolism in situ. This core system was used to
      study the kinetics of growth and the mode of penetration of strains of
      Escherichia coli through anaerobic, nutrient-saturated, fine Ottawa sand
      (permeability of 7.0 microns2 and porosity of 37%) under static conditions. The
      in situ rate of growth of a wild-type, motile, chemotactic strain, RW262, was two
      times slower inside cores than it was in liquid cultures. The mode of metabolism
      of galactose by strain RW262 was not altered inside cores, as acetate was the
      only product detected either inside the cores or in liquid cultures. Without
      applied advective force, strain RW262 grew exponentially and moved through cores
      at a rate of about 0.1 m/day. The cell population moved through cores in a band
      like fashion, as the front of the moving cells consisted of high cell
      concentrations (greater than 10(5) cells per ml). Until the breakthrough of the
      cells occurred, galactose consumption and acetate production were observed only
      in the proximal sections of the core, showing that the cell propagation preceded
      the complete depletion of the substrate or the accumulation of large amounts of
      products.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285678
TI  - Isotactic polypropylene biodegradation by a microbial community: physicochemical
      characterization of metabolites produced.
AB  - From a selective enrichment culture prepared with different soil samples on
      starch-containing polyethylene we isolated four microaerophilic microbial
      communities able to grow on this kind of plastic with no additional carbon
      source. One consortium, designated community 3S, was tested with pure isotactic
      polypropylene to determine whether the consortium was able to degrade this
      polymer. Polypropylene strips were incubated for 5 months in a mineral medium
      containing sodium lactate and glucose in screw-cap bottles. Dichloromethane crude
      extracts of the cultures revealed that the weight of extracted materials
      increased with incubation time, while the polypropylene sample weight decreased.
      The extracted materials were characterized by performing chromatographic and
      spectral analyses (thin-layer chromatography, liquid chromatography, gas
      chromatography-mass spectrometry, infrared spectrometry, nuclear magnetic
      resonance). Three main fractions were detected and analyzed; a mixture of
      hydrocarbons at different degrees of functionalization was found together with a
      mixture of aromatic esters, as the plasticizers usually added to polyolefinic
      structures.

PMID- 8285679
TI  - A substrate-dependent biological containment system for Pseudomonas putida based
      on the Escherichia coli gef gene.
AB  - A model substrate-dependent suicide system to biologically contain Pseudomonas
      putida KT2440 is reported. The system consists of two elements. One element
      carries a fusion between a synthetic lac promoter (PA1-04/03) and the gef gene,
      which encodes a killing function. This element is contained within a
      transposaseless mini-Tn5 transposon so that it can be integrated at random
      locations on the Pseudomonas chromosome. The second element, harbored by plasmid
      pCC102, is designed to control the first and bears a fusion between the promoter
      of the P. putida TOL plasmid-encoded meta-cleavage pathway operon (Pm) and the
      lacI gene, encoding the Lac repressor, plus xylS2, coding for a positive
      regulator of Pm. In liquid culture under optimal growth conditions and in sterile
      and nonsterile soil microcosms, P. putida KT2440 (pWWO) bearing the containment
      system behaves as designed. In the presence of a XylS effector, such as m
      methylbenzoate, the LacI protein is synthesized, preventing the expression of the
      killing function. In the absence of effectors, expression of the PA1-04/03::gef
      cassette is no longer prevented and a high rate of cell killing is observed.
      Fluctuation test analyses revealed that mutants resistant to cell killing arise
      at a frequency of around 10(-5) to 10(-6) per cell per generation. Mutations are
      linked to the killing element rather than to the regulatory one. In bacteria
      bearing two copies of the killing cassette, the rate of appearance of mutants
      resistant to killing decreased to as low as 10(-8) per cell per generation.

PMID- 8285680
TI  - Genetic improvement of Escherichia coli for enhanced biological removal of
      phosphate from wastewater.
AB  - The ability of Escherichia coli MV1184 to accumulate inorganic phosphate (Pi) was
      enhanced by manipulating the genes involved in the transport and metabolism of
      Pi. The high-level Pi accumulation was achieved by modifying the genetic
      regulation and increasing the dosage of the E. coli genes encoding polyphosphate
      kinase (ppk), acetate kinase (ackA), and the phosphate-inducible transport system
      (pstS, pstC, pstA, and pstB). Acetate kinase was employed as an ATP regeneration
      system for polyphosphate synthesis. Recombinant strains, which contained either
      pBC29 (carrying ppk) or pEP02.2 (pst operon), removed approximately two- and
      threefold, respectively, more Pi from minimal medium than did the control strain.
      The highest rates of Pii removal were obtained by strain MV1184 containing pEP03
      (ppk and ackA). However, unlike the control strain, MV1184 (pEP03) released Pi to
      the medium after growth had stopped. Drastic changes in growth and Pi uptake were
      observed when pBC29 (ppk) and pEP02.2 (pst operon) were introduced simultaneously
      into MV1184. Even though growth of this recombinant was severely limited in
      minimal medium, the recombinant could remove approximately threefold more Pi than
      the control strain. Consequently, the phosphorus content of this recombinant
      reached a maximum of approximately 16% on a dry weight basis (49% as phosphate).

PMID- 8285681
TI  - Cloning and sequencing of agaA, a unique agarase 0107 gene from a marine
      bacterium, Vibrio sp. strain JT0107.
AB  - An agarase gene (agaA) was cloned from genomic DNA of Vibrio sp. strain JT0107.
      An open reading frame of 2,985 nucleotides gave a primary translation product
      composed of the mature protein, agarase 0107 (975 amino acid residues, with a
      molecular weight of 105,271) and a signal peptide of 20 amino acid residues at
      the N terminus. Comparison of the deduced amino acid sequence of agarase 0107
      with those of Streptomyces coelicolor and Pseudomonas atlantica suggests that
      these enzymes share two regions in common. The AgaA protein which was expressed
      in Escherichia coli had the agarase activity. Agarase 0107 hydrolyzes not only
      agarose but also neoagarotetraose [O-3,6-anhydro-alpha-L-galactopyranosyl (1-->3)
      O-beta-D-galactopyranosyl(1-->4)-O-3,6-anhydro-alpha-L-galact opy ranosyl (1-->3)
      D-galactose] to yield neoagarobiose [O-3,6-anhydro-alpha-L-galactopyranosyl(1-
      >3)-D-galactose]. This is a quite unique characteristic for a beta-agarase.

PMID- 8285682
TI  - Involvement of cytochromes in the anaerobic biotransformation of
      tetrachloromethane by Shewanella putrefaciens 200.
AB  - Shewanella putrefaciens 200 is an obligate respiratory bacterium that can utilize
      a variety of terminal electron acceptors, e.g., NO3-, NO2-, Fe(III), and
      trimethylamine N-oxide, in the absence of O2. The bacterium catalyzed the
      reductive transformation of tetrachloromethane (CT) under anaerobic conditions.
      The only identified product was trichloromethane (CF), but CF production was not
      stoichiometric. No dichloromethane, chloromethane, or methane was produced. A
      chloride mass balance indicated that fully dechlorinated products were not
      formed. Studies with [14C]CT suggested that a portion of the transformed CT
      reacted with biomass to form unidentified soluble and insoluble products.
      Intermediate production of a trichloromethyl radical can explain observed product
      distribution without significant CO2 formation. Evidence suggests that
      respiratory c-type cytochromes are responsible for the dehalogenation ability of
      S. putrefaciens 200. Previous growth under microaerobic conditions ([O2], < 2.5
      microM) results in (i) a 2.6-fold increase in specific heme c content and (ii) a
      2.3-fold increase in specific rates of anaerobic CT transformation. Manipulation
      of heme content by growth on iron-free medium or medium amended with delta
      aminolevulinic acid showed that CT transformation rates increase with increases
      in specific heme c content. Transformation of CT is inhibited by CO.
      Dehalogenation studies with periplasmic, cytoplasmic, and membrane fractions
      indicated that only periplasmic and membrane fractions possessed dehalogenation
      ability. Cytochromes c were the predominant cytochromes present. Membranes were
      also found to contain smaller amounts of cytochrome b. Observed CT transformation
      patterns are consistent with a cometabolic description involving fortuitous CT
      reduction by reduced c-type cytochromes.

PMID- 8285683
TI  - Characterization of enzymatic reduction of hexavalent chromium by Escherichia
      coli ATCC 33456.
AB  - Chromium reduction by Escherichia coli ATCC 33456 quantitatively transferred
      hexavalent chromium, Cr(VI), to trivalent chromium, Cr(III). The reduced chromium
      was predominantly present in the external medium. Supernatant fluids of cell
      extract, obtained by centrifugation at 12,000 and 150,000 x g, showed almost the
      same Cr(VI) reduction activity, indicating that Cr(VI) reduction by E. coli ATCC
      33456 was a largely soluble reductase activity. In studies with respiratory
      inhibitors, no inhibitory effects on aerobic and anaerobic Cr(VI) reduction were
      demonstrated by addition of cyanide, azide, and rotenone into both intact cell
      cultures and supernatant fluids of E. coli ATCC 33456. Although cytochromes b and
      d were identified in the membrane fraction of cell extracts, Cr(VI) was not
      reduced by the membrane fraction alone. The cytochrome difference spectra
      analysis also indicated that these cytochromes of the respiratory chain require
      the presence of the soluble Cr(VI) reductase to mediate electron transport to
      Cr(VI). Stimulation of Cr(VI) reduction by an uncoupler, 2,4-dinitrophenol,
      indicated that the respiratory-chain-linked electron transport to Cr(VI) was
      limited by the rate of dissipation of the proton motive force.

PMID- 8285684
TI  - A new mechanism for the aerobic catabolism of dimethyl sulfide.
AB  - Aerobic degradation of dimethyl sulfide (DMS), previously described for
      thiobacilli and hyphomicrobia, involves catabolism to sulfide via methanethiol
      (CH3SH). Methyl groups are sequentially eliminated as HCHO by incorporation of O2
      catalyzed by DMS monooxygenase and methanethiol oxidase. H2O2 formed during CH3SH
      oxidation is destroyed by catalase. We recently isolated Thiobacillus strain ASN
      1, which grows either aerobically or anaerobically with denitrification on DMS.
      Comparative experiments with Thiobacillus thioparus T5, which grows only
      aerobically on DMS, indicate a novel mechanism for aerobic DMS catabolism by
      Thiobacillus strain ASN-1. Evidence that both organisms initially attacked the
      methyl group, rather than the sulfur atom, in DMS was their conversion of ethyl
      methyl sulfide to ethanethiol. HCHO transiently accumulated during the aerobic
      use of DMS by T. thioparus but not with Thiobacillus strain ASN-1. Catalase
      levels in cells grown aerobically on DMS were about 100-fold lower in
      Thiobacillus strain ASN-1 than in T. thioparus T5, suggesting the absence of H2O2
      formation during DMS catabolism. Also, aerobic growth of T. thioparus T5 on DMS
      was blocked by the catalase inhibitor 3-amino-1,2,4-triazole whereas that of
      Thiobacillus strain ASN-1 was not. Methyl butyl ether, but not CHCl3, blocked DMS
      catabolism by T. thioparus T5, presumably by inhibiting DMS monooxygenase and
      perhaps methanethiol oxidase. In contrast, DMS metabolism by Thiobacillus strain
      ASN-1 was unaffected by methyl butyl ether but inhibited by CHCl3. DMS catabolism
      by Thiobacillus strain ASN-1 probably involves methyl transfer to a cobalamin
      carrier and subsequent oxidation as folate-bound intermediates.

PMID- 8285685
TI  - Dichloromethane as the sole carbon source for an acetogenic mixed culture and
      isolation of a fermentative, dichloromethane-degrading bacterium.
AB  - Dichloromethane (DCM) is utilized by the strictly anaerobic, acetogenic mixed
      culture DM as a sole source of carbon and energy for growth. Growth with DCM was
      linear, and cell suspensions of the culture degraded DCM with a specific activity
      of 0.47 mkat/kg of protein. A mass balance of 2 mol of chloride and 0.42 mol of
      acetate per mol of DCM was observed. The dehalogenation reaction showed similar
      specific activities under both anaerobic and aerobic conditions. Radioactivity
      from [14C]DCM in cell suspensions was recovered largely as 14CO2 (58%),
      [14C]acetate (23%), and [14C]formate (11%), which subsequently disappeared. This
      suggested that formate is a major intermediate in the pathway from DCM to
      acetate. Efforts to isolate from culture DM a pure culture capable of anaerobic
      growth with DCM were unsuccessful, although overall acetogenesis and the partial
      reactions are thermodynamically favorable. We then isolated bacterial strains
      DMA, a strictly anaerobic, gram-positive, endospore-forming rod, and DMB, a
      strictly anaerobic, gram-negative, endospore-forming homoacetogen, from culture
      DM. Both strain DMB and Methanospirillum hungatei utilized formate as a source of
      carbon and energy. Coculture of strain DMA with either M. hungatei or strain DMB
      in solid medium with DCM as the sole added source of carbon and energy was
      observed. These data support a tentative scheme for the acetogenic fermentation
      of DCM involving interspecies formate transfer from strain DMA to the acetogenic
      bacterium DMB or to the methanogen M. hungatei.

PMID- 8285686
TI  - Natural occurrence of Fusarium mycotoxins (trichothecenes and zearalenone) in
      barley and corn in Korea.
AB  - Barley is produced in four provinces, Chonbuk, Chonnam, Kyungbuk, and Kyungnam,
      and corn is mainly produced in the Kangwon province in Korea. The natural
      occurrence of Fusarium mycotoxins was surveyed in 39 barley and 46 corn samples
      from different areas. Five 8-ketotrichothecenes, namely deoxynivalenol (DON),
      nivalenol (NIV), 4-acetylnivalenol (4-ANIV), 3-acetyldeoxynivalenol (3-ADON), and
      4,15-diacetylnivalenol (4,15-DANIV), and zearalenone (ZEA) were detected in
      barley. DON, NIV, and ZEA were the major contaminants in barley, with mean levels
      of 170, 1,011, and 287 ng/g, respectively. On the other hand, DON, 15
      acetyldeoxynivalenol (15-ADON), NIV, 4-ANIV, 4,15-DANIV, and ZEA were detected in
      corn samples. DON and 15-ADON were the major contaminants in corn, with mean
      levels of 310 and 297 ng/g, respectively. The survey indicated that the natural
      occurrence of monoacetyl-DON and the ratios of NIV to DON in two cereals were
      different. In addition, this is the first report of the natural occurrence of
      4,15-DANIV in cereals.

PMID- 8285687
TI  - Transfer of neurotoxigenicity from Clostridium butyricum to a nontoxigenic
      Clostridium botulinum type E-like strain.
AB  - Two Clostridium butyricum strains from infant botulism cases produce a toxic
      molecule very similar to C. botulinum type E neurotoxin. Chromosomal, plasmid,
      and bacteriophage DNAs of toxigenic and nontoxigenic strains of C. butyricum and
      C. botulinum type E were probed with (i) a synthesized 30-mer oligonucleotide
      encoding part of the L chain of type E botulinum toxin and (ii) the DNA of phages
      lysogenizing these cultures. The toxin gene probe hybridized to the chromosomal
      DNA of toxigenic strains but not to their plasmid DNA. All toxigenic and most
      nontoxigenic strains tested were lysogenized by a prophage on the chromosome.
      Prophages of toxigenic strains, irrespective of species, had related or identical
      DNAs which differed from the DNAs of prophages in nontoxigenic strains. The
      prophage of toxigenic strains was adjacent or close to the toxin gene on the
      chromosome. Phage DNAs purified from toxigenic strains did not hybridize with the
      toxin gene probe but could act as the template of the polymerase chain reaction
      to amplify the toxin gene. The toxin gene was not transferred between C.
      botulinum and C. butyricum (either direction) when different pairs of a possible
      gene donor and a recipient strain were grown as mixed cultures. Nontoxigenic C.
      butyricum or C. botulinum type E-like strains did not become toxigenic when grown
      in broth containing the phage induced from a toxigenic strain of the other
      species.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285688
TI  - Use of 5-cyano-2,3-ditolyl tetrazolium chloride for quantifying planktonic and
      sessile respiring bacteria in drinking water.
AB  - Direct microscopic quantification of respiring (i.e., viable) bacteria was
      performed for drinking water samples and biofilms grown on different opaque
      substrata. Water samples or biofilms developed in flowing drinking water were
      incubated with the vital redox dye 5-cyano-2,3-ditolyl tetrazolium chloride (CTC)
      and R2A medium. One hour of incubation with 0.5 mM CTC was sufficient to obtain
      intracellular reduction of CTC to the insoluble fluorescent formazan (CTF)
      product, which was indicative of cellular respiratory (i.e., electron transport)
      activity. This result was obtained with both planktonic and biofilm-associated
      cells. Planktonic bacteria were captured on 0.2-microns-pore-size polycarbonate
      membrane filters and examined by epifluorescence microscopy. Respiring cells
      containing CTF deposits were readily detected and quantified as red-fluorescing
      objects on a dark background. The number of CTC-reducing bacteria was
      consistently greater than the number of aerobic CFU determined on R2A medium.
      Approximately 1 to 10% of the total planktonic population (determined by
      counterstaining with 4,6-diamidino-2-phenylindole) were respirometrically active.
      The proportion of respiring bacteria in biofilms composed of drinking water
      microflora was greater, ranging from about 5 to 35%, depending on the substratum.
      Respiring cells were distributed more or less evenly in biofilms, as demonstrated
      by counterstaining with 4,6-diamidino-2-phenylindole. The amount of CTF deposited
      in single cells of Pseudomonas putida that formed monospecies biofilms was
      quantified by digital image analysis and used to indicate cumulative respiratory
      activity. These data indicated significant cell-to-cell variation in respiratory
      activity and reduced electron transport following a brief period of nutrient
      starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285689
TI  - Enhanced biodegradation of polychlorinated biphenyls after site-directed
      mutagenesis of a biphenyl dioxygenase gene.
AB  - Biphenyl dioxygenase catalyzes the first step in the aerobic degradation of
      polychlorinated biphenyls (PCBs). The nucleotide and amino acid sequences of the
      biphenyl dioxygenases from two PCB-degrading strains (Pseudomonas sp. strain
      LB400 and Pseudomonas pseudoalcaligenes KF707) were compared. The sequences were
      found to be nearly identical, yet these enzymes exhibited dramatically different
      substrate specificities for PCBs. Site-directed mutagenesis of the LB400 bphA
      gene resulted in an enzyme combining the broad congener specificity of LB400 with
      increased activity against several congeners characteristic of KF707. These data
      strongly suggest that the BphA subunit of biphenyl dioxygenase plays an important
      role in determining substrate selectivity. Further alteration of this enzyme can
      be used to develop a greater understanding of the structural basis for congener
      specificity and to broaden the range of degradable PCB congeners.

PMID- 8285690
TI  - Derivation of DNA probes for enumeration of a specific strain of Lactobacillus
      acidophilus in piglet digestive tract samples.
AB  - Four DNA probes were derived that hybridized specifically to DNA from
      Lactobacillus acidophilus O. The probes were constructed by randomly cloning
      lactobacillus DNA in plasmid vector pBR322. Two of the probes (pSR1 and pSR2)
      were composed of vector and plasmid DNA inserts (3.6 and 1.6 kb, respectively);
      the others (pSR3 and pSR4) were composed of vector and chromosomally derived
      inserts (6.9 and 1.4 kb, respectively). The probes were used to enumerate, by
      colony hybridization, strain O in digestive tract samples collected from piglets
      inoculated 24 hours previously with a culture of the strain. The probes did not
      hybridize to DNA from lactobacilli inhabiting the digestive tract of uninoculated
      piglets. Strain O made up about 10% of the total lactobacillus population of the
      pars esophagea and about 20% of the population in other digestive tract samples.

PMID- 8285691
TI  - Gene cloning, sequence analysis, purification, and characterization of a
      thermostable aminoacylase from Bacillus stearothermophilus.
AB  - A genomic DNA fragment encoding aminoacylase activity of the eubacterium Bacillus
      stearothermophilus was cloned into Escherichia coli. Transformants expressing
      aminoacylase activity were selected by their ability to complement E. coli
      mutants defective in acetylornithine deacetylase activity, the enzyme that
      converts N-acetylornithine to ornithine in the arginine biosynthetic pathway. The
      2.3-kb cloned fragment has been entirely sequenced. Analysis of the sequence
      revealed two open reading frames, one of which encoded the aminoacylase. B.
      stearothermophilus aminoacylase, produced in E. coli, was purified to near
      homogeneity in three steps, one of which took advantage of the intrinsic
      thermostability of the enzyme. The enzyme exists as homotetramer of 43-kDa
      subunits as shown by cross-linking experiments. The deacetylating capacity of
      purified aminoacylase varies considerably depending on the nature of the amino
      acid residue in the substrate. The enzyme hydrolyzes N-acyl derivatives of
      aromatic amino acids most efficiently. Comparison of the predicted amino acid
      sequence of B. stearothermophilus aminoacylase with those of eubacterial
      acetylornithine deacylase, succinyldiaminopimelate desuccinylase,
      carboxypeptidase G2, and eukaryotic aminoacylase I suggests a common origin for
      these enzymes.

PMID- 8285692
TI  - A soluble Bacillus cereus cytochrome P-450cin system catalyzes 1,4-cineole
      hydroxylations.
AB  - A cytochrome P-450-dependent monooxygenase system that catalyzes the
      stereospecific hydroxylation of the monoterpene substrate 1,4-cineole was
      demonstrated in cell-free preparations of Bacillus cereus UI-1477. 1,4-Cineole
      hydroxylations were catalyzed by a 100,000 x g (1-h)-centrifuging soluble, hexane
      inducible enzyme that activated and incorporated molecular oxygen into
      hydroxylated products; required NADH; was inhibited by SKF-525A, imidazole,
      metyrapone, and octylamine; and displayed a 452-nm peak in the carbon monoxide
      difference absorption spectrum. The constant 7:1 ratio of endo/exo alcohol
      products formed when 1,4-cineole was hydroxylated by normal cells, hexane-induced
      cells, and cell extracts suggested that a single enzyme designated cytochrome P
      450cin was responsible for both reactions.

PMID- 8285693
TI  - Secretion of streptavidin from Bacillus subtilis.
AB  - Streptavidin is an extracellular tetrameric protein produced by Streptomyces
      avidinii. A series of hybrid gene fusions consisting of Bacillus signal peptide
      coding regions fused to the mature streptavidin sequence were constructed. B.
      subtilis strains harboring these plasmids accumulate a tetrameric streptavidin in
      the growth medium. The properties of the streptavidin produced by B. subtilis are
      similar to those of the streptavidin produced by S. avidinii. B. subtilis strains
      carrying the various fusions can be grown to a high cell density in a biotin-free
      medium. Thus, B. subtilis represents an alternate host system for the production
      of streptavidin.

PMID- 8285694
TI  - Molecular analysis of the lactacin F operon.
AB  - Lactacin F is a nonlantibiotic, heat-stable, peptide bacteriocin produced by
      Lactobacillus johnsonii VPI11088. Molecular analysis of the lactacin F DNA region
      characterized a small operon that codes for three open reading frames, designated
      lafA, lafX, and ORFZ. The peptide encoded by lafA, the lactacin F structural
      gene, was compared with various peptide bacteriocins from lactic acid bacteria,
      and similarities were identified in the amino and carboxy termini of the
      propeptides. Site-directed mutagenesis of the LafA precursor at the two glycine
      residues in positions -1 and -2 defined an essential motif for processing of
      mature lactacin F. The involvement of the peptides encoded by lafX and ORFZ in
      bacteriocin expression was investigated by subcloning various fragments from the
      lactacin F region into the shuttle vector pGKV210. In addition to lafA,
      expression of lafX is essential to lactacin F activity. The lactacin F operon
      resembles the genetic organization of lactococcin M. Although no function has
      been assigned to ORFZ by genetic analysis, both peptide Z and the lactococcin M
      immunity protein are predicted to be integral membrane proteins with four
      putative transmembrane segments. Lactacin F activity, defined by bactericidal
      action on Lactobacillus delbrueckii, is dependent on the expression of two genes,
      lafA and lafX.

PMID- 8285695
TI  - Role of the CryIVD polypeptide in the overall toxicity of Bacillus thuringiensis
      subsp. israelensis.
AB  - The gene encoding the CryIVD protein of B. thuringiensis subsp. israelensis
      crystals was disrupted by in vivo recombination. The toxicity of the CryIVD
      protein-free inclusions was similar to that of the wild-type crystals on
      Anopheles stephensi larvae but was half the wild-type toxicity on Culex pipiens
      and Aedes aegypti larvae.

PMID- 8285696
TI  - Biodegradation and transformation of 4,4'- and 2,4-dihalodiphenyl ethers by
      Sphingomonas sp. strain SS33.
AB  - The bacterium Sphingomonas sp. strain SS33, obtained from parent diphenyl ether
      mineralizing strain SS3 (S. Schmidt, R.-M. Wittich, D. Erdmann, H. Wilkes, W.
      Francke, and P. Fortnagel, Appl. Environ. Microbiol. 58:2744-2750, 1992) after
      several weeks of adaptation on 4,4'-difluorodiphenyl ether as the new target
      compound, also utilized 4,4'-dichlorodiphenyl ether for growth. Intermediary
      halocatechols were also mineralized via the ortho pathway by type I enzymes. 4,4'
      Dibromodiphenyl ether was not used as a carbon source although transformation by
      resting cells yielded mononuclear haloaromatic compounds, such as 4-bromophenol
      and 4-bromocatechol. The same was true for the conversion of 2,4-dichlorodiphenyl
      ether, which yielded the respective (halo-) phenols and (halo-) catechols.

PMID- 8285697
TI  - Acylated proteins in Borrelia hermsii, Borrelia parkeri, Borrelia anserina, and
      Borrelia coriaceae.
AB  - Borrelia hermsii, Borrelia parkeri, Borrelia anserina, and Borrelia coriaceae
      produced several lipoproteins identified by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and fluorography of bacteria grown in [3H]palmitate. Five
      major acylated proteins were demonstrated by sequential alkaline and acid
      hydrolysis. High-pressure liquid chromatography of isolated proteins confirmed
      that covalently bound radioactivity was represented by fatty acids.

PMID- 8285698
TI  - Temporal expression of the major lignin peroxidase genes of Phanerochaete
      chrysosporium.
AB  - DNA probes specific for the genes encoding major lignin peroxidase (LIP) isozymes
      H2, H8, and H10 of Phanerochaete chrysosporium were constructed. These probes
      were used to study the temporal expression of the three lip genes in defined low
      nitrogen medium. H2 gene transcripts were produced at high levels on days 4, 5,
      and 7 and at low levels on day 6, while the H8 gene transcripts peaked on day 4
      and were produced in substantially lower amounts thereafter. H10 transcripts, on
      the other hand, peaked on day 4, dropped precipitously on day 5, and were barely
      detectable on days 6 and 7. There was no precise correlation between lip
      transcript and isozyme levels.

PMID- 8285699
TI  - A model system for the investigation of heterologous protein secretion pathways
      in Lactococcus lactis.
AB  - The capacity of recombinant strains of Lactococcus lactis to secrete a
      heterologous protein was investigated by constructing two expression-secretion
      vectors (pLET2 and pLET3) for use with a lactococcal gene expression system
      driven by the highly active T7 RNA polymerase. The vectors incorporated different
      lactococcal secretion leaders and translation initiation sequences. When tetanus
      toxin fragment C (TTFC) was used as a test protein, the quantities of TTFC
      produced by the pLET2-TTFC strain exceeded the rate of secretion of TTFC into the
      growth medium. However, nearly all of the soluble TTFC associated with the cell
      (3.4%) was translocated through the cell membrane. The pLET3-TTFC strain did not
      accumulate TTFC intracellularly and exhibited growth characteristics and
      viability identical to the growth characteristics and viability of the control
      strain. This strain secreted approximately 2.9 mg of TTFC per liter into the
      growth medium after 6 h of growth under test tube conditions. Our results
      indicate that L. lactis is capable of secreting substantial amounts of
      heterologous protein and also confirm the findings of other workers that the cell
      wall may serve as a functional barrier to the diffusion of some secreted proteins
      into the growth medium.

PMID- 8285700
TI  - Use of genomic probes to detect hepatitis A virus and enterovirus RNAs in wild
      shellfish and relationship of viral contamination to bacterial contamination.
AB  - Genomic probes were used to investigate hepatitis A virus (HAV) and enterovirus
      RNAs in two types of shellfish from natural beds (Atlantic coast, France). After
      elution concentration, nucleic acid extracted by proteinase K and purified by
      phenol-chloroform and ethanol precipitation was assayed by dot blot
      hybridization. The probes used were a specific HAV probe corresponding to the 3'
      end (3D polymerase coding region) and an enterovirus probe corresponding to the
      5' noncoding region. The method was first tested under experimental conditions by
      using virus-spiked shellfish before being applied under field conditions. Our
      results show that shellfish were highly contaminated: enterovirus and HAV RNAs
      were found in 63 and 67%, respectively, of samples examined with the riboprobes.
      On the same site, viral (HAV and enterovirus) RNAs were found in a larger
      fraction of cockles than mussels. Statistical tests of dependence showed no
      relationship between viral contamination and bacterial contamination (evaluated
      by fecal coliform counts).

PMID- 8285701
TI  - Nylon oligomer degradation gene, nylC, on plasmid pOAD2 from a Flavobacterium
      strain encodes endo-type 6-aminohexanoate oligomer hydrolase: purification and
      characterization of the nylC gene product.
AB  - A new type of nylon oligomer degradation enzyme (EIII) was purified from an
      Escherichia coli clone harboring the EIII gene (nylC). This enzyme hydrolyzed the
      linear trimer, tetramer, and pentamer of 6-aminohexanoate by an endo-type
      reaction, and this specificity is different from that of the EI (nylA gene
      product) and EII (nylB gene product). Amino acid sequencing and sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of the purified EIII demonstrated that
      the enzyme is made of two polypeptide chains arising from an internal cleavage
      between amino acid residues 266 and 267.

PMID- 8285702
TI  - Effect of phosphate concentration on production of tetrodotoxin by Alteromonas
      tetraodonis.
AB  - Tetrodotoxin production by Alteromonas tetraodonis occurred during the stationary
      phase of growth and was regulated by phosphate concentration; toxin production
      was repressed if phosphate was added at the onset of stationary phase and was
      over 100-fold greater in phosphate-limited cultures than in cultures in which
      phosphate was not limiting.

PMID- 8285703
TI  - Nutritional aspects of cytotoxin production by Clostridium difficile.
AB  - Arginine was the only amino acid used by Clostridium difficile that permitted
      cytotoxin synthesis in a peptone-based medium. Synthesis of cytotoxin was delayed
      when glucose was used as the substrate. Addition of rifampin or puromycin to
      cultures prior to release of cytotoxin inhibited the release of cytotoxin,
      suggesting that a protein essential for cytotoxin release is synthesized after
      cytotoxin is synthesized.

PMID- 8285704
TI  - Differential expression of conserved protease genes in crucifer-attacking
      pathovars of Xanthomonas campestris.
AB  - Strains of Xanthomonas campestris pathovars armoraciae and raphani, which cause
      leaf spotting diseases in brassicas, produce a major extracellular protease in
      liquid culture which was partially purified. The protease (PRT 3) was a zinc
      requiring metalloenzyme and was readily distinguishable from the two previously
      characterized proteases (PRT 1 and PRT 2) of X. campestris pv. campestris by the
      pattern of degradation of beta-casein and sensitivity to inhibitors. PRT 3 was
      produced at a low level in the vascular brassica pathogen X. campestris pv.
      campestris (five strains tested), in which PRT 1 and PRT 2 predominate. In
      contrast, expression of PRT 1, a serine protease, could not be detected in the
      six tested strains of the leaf spotting mesophyll pathogens. However, all these
      strains had DNA fragments which hybridized to a prtA probe and which probably
      carry a functional prtA (the structural gene for PRT 1). The structural gene for
      PRT 3 (prtC) was cloned by screening a genomic library of X. campestris pv.
      raphani in a protease-deficient X. campestris pv. campestris strain. Subcloning
      and Tn5 mutagenesis located the structural gene to 1.2 kb of DNA. DNA fragments
      which hybridized to the structural gene were found in all strains of the crucifer
      attacking X. campestris pathovars tested as well as in a number of other
      pathovars. Experiments in which the pattern of protease production of the
      pathovars was manipulated by introduction of cloned genes into heterologous
      pathovars suggested that no determinative relationship exists between the pattern
      of protease gene expression and the (vascular or mesophyllic) mode of
      pathogenesis.

PMID- 8285705
TI  - Ubiquity of lignin-degrading peroxidases among various wood-degrading fungi.
AB  - Phanerochaete chrysosporium is rapidly becoming a model system for the study of
      lignin biodegradation. Numerous studies on the physiology, biochemistry,
      chemistry, and genetics of this system have been performed. However, P.
      chrysosporium is not the only fungus to have a lignin-degrading enzyme system.
      Many other ligninolytic species of fungi, as well as other distantly related
      organisms which are known to produce lignin peroxidases, are described in this
      paper. In this study, we demonstrated the presence of the peroxidative enzymes in
      nine species not previously investigated. The fungi studied produced significant
      manganese peroxidase activity when they were grown on an oak sawdust substrate
      supplemented with wheat bran, millet, and sucrose. Many of the fungi also
      exhibited laccase and/or glyoxal oxidase activity. Inhibitors present in the
      medium prevented measurement of lignin peroxidase activity. However, Western
      blots (immunoblots) revealed that several of the fungi produced lignin peroxidase
      proteins. We concluded from this work that lignin-degrading peroxidases are
      present in nearly all ligninolytic fungi, but may be expressed differentially in
      different species. Substantial variability exists in the levels and types of
      ligninolytic enzymes produced by different white not fungi.

PMID- 8285706
TI  - Detection of polychlorinated biphenyl degradation genes in polluted sediments by
      direct DNA extraction and polymerase chain reaction.
AB  - It was the aim of this study to specifically detect the DNA sequences for the
      bphC gene, the meta-cleavage enzyme of the aerobic catabolic pathway for biphenyl
      and polychlorinated biphenyl degradation, in aquatic sediments without prior
      cultivation of microorganisms by using extraction of total DNA, PCR amplification
      of bphC sequences, and detection with specific gene probes. The direct DNA
      extraction protocol used was modified to enhance lysis efficiency. Crude extracts
      of DNA were further purified by gel filtration, which yielded DNA that could be
      used for the PCR. PCR primers were designed for conserved regions of the bphC
      gene from a sequence alignment of five known sequences. The specificity of PCR
      amplification was verified by using digoxigenin-labeled DNA probes which were
      located internal to the amplified gene sequence. The detection limit for the bphC
      gene of Pseudomonas paucimobilis Q1 and Pseudomonas sp. strain LB400 was 100
      cells per g (wet weight) or approximately five copies of the target sequence per
      PCR reaction mixture. In total-DNA extracts of aerobic top layers of sediment
      samples obtained from three different sampling sites along the Elbe River, which
      has a long history of anthropogenic pollution, Pseudomonas sp. strain LB 400-like
      sequences for the bphC gene were detected, but P. paucimobilis Q1 sequences were
      not detected. No bphC sequences were detected in an unpolluted lake sediment. A
      restriction analysis did not reveal any heterogeneity in the PCR product, and the
      possibility that sequences highly related to the bphC gene (namely, nahC and
      todE) were present was excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285707
TI  - Aerobic and anaerobic degradation of a range of alkyl sulfides by a denitrifying
      marine bacterium.
AB  - A pure culture of a bacterium was obtained from a marine microbial mat by using
      an anoxic medium containing dimethyl sulfide (DMS) and nitrate. The isolate grew
      aerobically or anaerobically as a denitrifier on alkyl sulfides, including DMS,
      dimethyl disulfide, diethyl sulfide (DES), ethyl methyl sulfide, dipropyl
      sulfide, dibutyl sulfide, and dibutyl disulfide. Cells grown on an alkyl sulfide
      or disulfide also oxidized the corresponding thiols, namely, methanethiol,
      ethanethiol, propanethiol, or butanethiol. Alkyl sulfides were metabolized by
      induced or derepressed cells with oxygen, nitrate, or nitrite as electron
      acceptor. Cells grown on DMS immediately metabolized DMS, but there was a lag
      before DES was consumed; with DES-grown cells, DES was immediately used but DMS
      was used only after a lag. Chloramphenicol prevented the eventual use of DES by
      DMS-grown cells and DMS use by DES-grown cells, respectively, indicating separate
      enzymes for the metabolism of methyl and ethyl groups. Growth was rapid on
      formate, acetate, propionate, and butyrate but slow on methanol. The organism
      also grew chemolithotrophically on thiosulfate with a decrease in pH; growth
      required carbonate in the medium. Growth on sulfide was also carbonate dependent
      but slow. The isolate was identified as a Thiobacillus sp. and designated strain
      ASN-1. It may have utility for removing alkyl sulfides, and also nitrate,
      nitrite, and sulfide, from wastewaters.

PMID- 8285708
TI  - Efficacy of filter types for detecting Campylobacter jejuni and Campylobacter
      coli in environmental water samples by polymerase chain reaction.
AB  - A previously developed polymerase chain reaction (PCR) amplification of a target
      region in the flaA Campylobacter flagellin gene was evaluated and adapted for use
      with environmental water samples. The ability to detect Campylobacter jejuni or
      Campylobacter coli in seeded water samples was tested with various filters after
      concentration and freeze-thaw lysis of the bacterial cells. A nonradioactive
      probe for the amplified flagellin gene fragment detected as little as 1 to 10 fg
      of genomic DNA and as few as 10 to 100 viable C. jejuni cells per 100 ml of water
      filtered onto Fluoropore (Millipore Corp.) filters. No amplification was obtained
      with cellulose acetate filters, most likely because of binding of the DNA to the
      filter. Concentration and lysis of target cells on Fluoropore and Durapore
      (Millipore Corp.) filters allowed PCR to be performed in the same reaction tube
      without removing the filters. This methodology was then adapted for use with
      environmental water samples. The water supply to a broiler chicken production
      farm was suspected as the source of C. jejuni known to be endemic in grow-out
      flocks at the farm, despite the inability to culture the organisms by standard
      methods. The filtration-PCR method detected Campylobacter DNA in more than half
      of the farm water samples examined. Amplified campylobacter DNA was not detected
      in small volumes of regional surface water samples collected on a single occasion
      in February. The filtration-PCR amplification method provided a basis for
      detection of C. jejuni and C. coli in environmental waters with a high degree of
      specificity and sensitivity.

PMID- 8285709
TI  - Adhesion of human bifidobacterial strains to cultured human intestinal epithelial
      cells and inhibition of enteropathogen-cell interactions.
AB  - Thirteen human bifidobacterial strains were tested for their abilities to adhere
      to human enterocyte-like Caco-2 cells in culture. The adhering strains were also
      tested for binding to the mucus produced by the human mucus-secreting HT29-MTX
      cell line in culture. A high level of calcium-independent adherence was observed
      for Bifidobacterium breve 4, for Bifidobacterium infantis 1, and for three fresh
      human isolates from adults. As observed by scanning electron microscopy, adhesion
      occurs to the apical brush border of the enterocytic Caco-2 cells and to the
      mucus secreted by the HT29-MTX mucus-secreting cells. The bacteria interacted
      with the well-defined apical microvilli of Caco-2 cells without cell damage. The
      adhesion to Caco-2 cells of bifidobacteria did not require calcium and was
      mediated by a proteinaceous adhesion-promoting factor which was present both in
      the bacterial whole cells and in the spent supernatant of bifidobacterium
      culture. This adhesion-promoting factor appeared species specific, as are the
      adhesion-promoting factors of lactobacilli. We investigated the inhibitory effect
      of adhering human bifidobacterial strains against intestinal cell monolayer
      colonization by a variety of diarrheagenic bacteria. B. breve 4, B. infantis 1,
      and fresh human isolates were shown to inhibit cell association of
      enterotoxigenic, enteropathogenic, diffusely adhering Escherichia coli and
      Salmonella typhimurium strains to enterocytic Caco-2 cells in a concentration
      dependent manner. Moreover, B. breve 4 and B. infantis 1 strains inhibited, dose
      dependently, Caco-2 cell invasion by enteropathogenic E. coli, Yersinia
      pseudotuberculosis, and S. typhimurium strains.

PMID- 8285710
TI  - Characterization and structural analysis of the laccase I gene from the newly
      isolated ligninolytic basidiomycete PM1 (CECT 2971).
AB  - We have isolated and characterized the cDNA and genomic DNA coding for a
      phenoloxidase, laccase I, previously purified from culture supernatant of the
      newly isolated ligninolytic basidiomycete PM1 (CECT 2971). A cDNA library from
      basidiomycete PM1 was constructed, and laccase-encoding cDNAs were identified by
      screening with antiserum raised against the purified enzyme. The lac1 gene coding
      for the laccase was identified in a partial genomic library by using the isolated
      cDNA as a probe. Nucleotide sequence determination of the full-length cDNA
      revealed an open reading frame of 1,551 bp encoding a polypeptide of 517 amino
      acid residues with a putative signal peptide of 21 amino acid residues. Ten small
      introns interrupted the genomic DNA. A single 1.8-kb transcript mRNA was detected
      by Northern (RNA) blot analysis, and its 5' end maps to a position 51 bp upstream
      from the site of initiation of protein synthesis. Eukaryotic regulatory
      sequences, CAAT and TATA, were observed in the 5' flanking region, which also
      contains sequences similar to those of copper-regulated proteins. Comparative
      analysis of the predicted amino acid sequence showed that basidiomycete PM1
      laccase I had great similarity to the laccases from Coriolus versicolor, Coriolus
      hirsutus, and Phlebia radiata.

PMID- 8285711
TI  - Ozone inactivation of Cryptosporidium parvum in demand-free phosphate buffer
      determined by in vitro excystation and animal infectivity.
AB  - Inactivation of Cryptosporidium parvum oocysts by ozone was performed in ozone
      demand-free 0.05 M phosphate buffer (pH 6.9) in bench-scale batch reactors at 7
      and 22 degrees C. Ozone was added to each trial from a concentrated stock
      solution for contact times ranging from 5 to 15 min. The viability of the control
      and treated oocysts was determined by using in vitro excystation and infection in
      neonatal CD-1 mice. It was found that excystation consistently underestimated
      inactivation when compared with animal infectivity (P < or = 0.05). As
      inactivations increased, the difference between excystation and infectivity also
      increased. The inactivation kinetics of C. parvum by ozone deviated from the
      simple first-order Chick-Watson model and was better described by a nonlinear Hom
      model. The use of the Hom model for predicting inactivation resulted in a family
      of unique concentration and time values for each inactivation level rather than
      the simple CT product of the Chick-Watson model.

PMID- 8285712
TI  - Identification of endomycorrhizal fungi colonizing roots by fluorescent single
      strand conformation polymorphism-polymerase chain reaction.
AB  - A method to identify arbuscular endomycorrhizal fungi based on the amplification
      of portions of the nuclear gene coding for the small subunit rRNA is presented.
      By coupling the sensitivity of the polymerase chain reaction and the specificity
      afforded by taxon-specific primers, a variety of samples can be analyzed,
      including small amounts of colonized roots. Family-specific primers as well as
      generic primers are described and can be used to amplify small subunit rRNA
      fragments from endomycorrhizal fungi by polymerase chain reaction. The amplified
      products are then subjected to single-strand conformation polymorphism analysis
      to detect sequence differences. Among the advantages of this approach is the
      possibility of directly identifying the fungi inside field-collected roots,
      without having to rely on the fortuitous presence of spores. This technique
      should have obvious applications in the study of arbuscular endomycorrhizal fungi
      populations and allow closer examination of their host specificity.

PMID- 8285713
TI  - An enzyme-linked immunosorbent assay-based isolation procedure for verotoxigenic
      Escherichia coli.
AB  - A colony enzyme-linked immunosorbent assay using the hydrophobic grid membrane
      filter format was developed for the isolation of verotoxigenic Escherichia coli
      from human and food samples. The method utilizes monoclonal antibodies directed
      against the verotoxins and is sensitive to all verotoxin 1- and/or 2-producing
      serotypes. E. coli that produced a minimum of 2 x 10(2) and 2 x 10(3) 50%
      cytotoxic doses per ml of verotoxins 1 and 2, respectively, were detectable. In a
      method comparison using human stool specimens, this procedure isolated 29% more
      E. coli O157 than did the standard sorbitol-MacConkey agar procedure, with no
      false-positive reactions. When applied to meat, 11 of 20 samples positive for
      verotoxin by polymyxin extraction yielded verotoxigenic E. coli of a variety of
      serotypes including O157:H7. Four false positives were noted. This procedure
      provides a sensitive means for the isolation of verotoxigenic E. coli and should
      facilitate recovery of those serotypes that are otherwise indistinguishable from
      nonpathogenic strains.

PMID- 8285714
TI  - Fermentation of lactose by yeast cells secreting recombinant fungal lactase.
AB  - Strains of Saccharomyces cerevisiae transformed with a yeast multicopy expression
      vector carrying the cDNA for Aspergillus niger secretory beta-galactosidase under
      the control of ADH1 promoter and terminator were studied for their fermentation
      properties on lactose (V. Kumar, S. Ramakrishnan, T. T. Teeri, J. K. C. Knowles,
      and B. S. Hartley, Biotechnology 10:82-85, 1992). Lactose was hydrolyzed
      extracellularly into glucose and galactose, and both sugars were utilized
      simultaneously. Diauxic growth patterns were not observed. However, a typical
      biphasic growth was observed on a mixture of glucose and galactose under aerobic
      and anaerobic conditions with transformants of a haploid S. cerevisiae strain,
      GRF167. Polyploid distiller's yeast (Mauri) transformants were selected simply on
      the basis of the cloned gene expression on X-Gal (5-bromo-4-chloro-3-indolyl-beta
      D-galactopyranoside) plates. Rapid and complete lactose hydrolysis and higher
      ethanol (0.31 g/g of sugar) and biomass (0.24 g/g of sugar) production were
      observed with distiller's yeast grown under aerobic conditions. A constant
      proportion (10%) of the population retained the plasmid throughout the
      fermentation period (48 h). Nearly theoretical yields of ethanol were obtained
      under anaerobic conditions on lactose, glucose, galactose, and whey permeate
      media. However, the rate and the amount of lactose hydrolysis were lower under
      anaerobic than aerobic conditions. All lactose-grown cells expressed partial
      galactokinase activity.

PMID- 8285715
TI  - Virulence of an Escherichia coli O157:H7 sorbitol-positive mutant.
AB  - Virulence and pathogenicity of an Escherichia coli O157:H7 sorbitol-positive
      mutant were investigated with an infant rabbit animal model as well as a battery
      of in vitro assays. Total cell lysate protein profiles, outer membrane protein
      profiles, plasmid profiles, and levels of cytotoxic activity against Vero cells
      were similar in the wild-type and mutant strains. Both adhered to intestinal
      epithelial cells in culture and reacted with fluorescein isothiocyanate-labeled
      antiserum against E. coli O157:H7. The mutant appeared to be similar to the wild
      type in all respects except in its ability to ferment sorbitol. [14C]sorbitol
      uptake and sorbitol-6-phosphate dehydrogenase activities were notably increased
      in the mutant strain. Diarrhea developed in rabbits administered the wild-type
      strain and in those fed the sorbitol-positive mutant. There was greater bacterial
      attachment and mucosal damage in the cecum and large intestine than in the small
      intestine. Scanning electron microscopy revealed bacteria adhering as single
      cells and as aggregates closely associated with mucus. Mucosal lesions consisted
      of areas of tissue necrosis with sloughing of epithelial cells. By transmission
      electron microscopy, electron-dense necrotic epithelial cells were visible in
      areas where bacteria were present, and epithelial cell debris containing bacteria
      was observed between the villar luminal surfaces. Light microscopy of epithelial
      cells of intestinal sections of infected rabbits revealed noticeable vacuolation
      and spherical, pyknotic nuclei. These data indicate that the sorbitol-negative
      phenotype is not associated with the pathogenicity of E. coli O157:H7.

PMID- 8285716
TI  - Alteration of growth yield by overexpression of phosphoenolpyruvate carboxylase
      and phosphoenolpyruvate carboxykinase in Escherichia coli.
AB  - Phosphoenolpyruvate and oxaloacetate are key intermediates at the junction
      between catabolism and biosynthesis. Alteration of carbon flow at these branch
      points will affect the growth yield and the formation of products. We attempted
      to modulate the metabolic flow between phosphoenolpyruvate and oxaloacetate by
      overexpressing phosphoenolpyruvate carboxylase and phosphoenolpyruvate
      carboxykinase from a multicopy plasmid under the control of the tac promoter. It
      was found that overexpression of phosphoenolpyruvate carboxylase decreased the
      rates of glucose consumption and organic acid excretion, but the growth and
      respiration rates remained unchanged. Consequently, the growth yield on glucose
      was improved. This result indicates that the wild-type level of
      phosphoenolpyruvate carboxylase is not optimal for the most efficient glucose
      utilization in batch cultures. On the other hand, overexpression of
      phosphoenolpyruvate carboxykinase increased glucose consumption and decreased
      oxygen consumption relative to those levels required for growth. Therefore, the
      growth yield on glucose was reduced because of a higher rate of fermentation
      product excretion. These data provide useful insights into the regulation of
      central metabolism and facilitate further manipulation of pathways for metabolite
      production.

PMID- 8285717
TI  - Biodegradation, sorption, and transport of 2,4-dichlorophenoxyacetic acid in
      saturated and unsaturated soils.
AB  - The fate of an organic contaminant in soil depends on many factors, including
      sorption, biodegradation, and transport. The herbicide 2,4-dichlorophenoxyacetic
      acid (2,4-D) was used as a model compound to illustrate the impact of these
      interacting factors on the fate of an organic contaminant. Batch and column
      experiments performed with a sandy loam soil mixture under saturated and
      unsaturated conditions were used to determine the effects of sorption and
      biodegradation on the fate and transport of 2,4-D. Sorption of 2,4-D was found to
      have a slight but significant effect on transport of 2,4-D under saturated
      conditions (retardation factor, 1.8) and unsaturated conditions (retardation
      factor, 3.4). Biodegradation of 2,4-D was extensive under both batch and column
      conditions and was found to have a significant impact on 2,4-D transport in
      column experiments. In batch experiments, complete mineralization of 2,4-D (100
      mg kg-1) occurred over a 4-day period following a 3-day lag phase under both
      saturated and unsaturated conditions. The biodegradation rate parameters
      calculated for batch experiments were found to be significantly different from
      those estimated for column experiments.

PMID- 8285718
TI  - Kinetics of the persistence of chromosomal DNA from genetically engineered
      Escherichia coli introduced into soil.
AB  - Investigations to quantify bacterial survival and DNA persistence of a
      genetically engineered population of Escherichia coli introduced into soil
      microcosms were carried out. The survival of E. coli was monitored by plate
      counting and immunofluorescence methods, whereas the persistence of the DNA was
      evaluated by using a most-probable-number-polymerase chain reaction method.
      Whereas the E. coli population density declined below the plate-counting
      technique detection threshold (10(2) CFU.g-1) after 15 days, 10(3) extracellular
      and 5 x 10(5) total DNA target sequences were still detected after 40 days.
      Additionally, the E. coli cell counts fell below the detection limit of the
      immunofluorescence method (10(5) cells.g-1) before the end of the experiment.
      Colony hybridizations did not reveal gene transfer to the indigenous microflora.
      These results confirm the persistence of residual E. coli target sequences that
      could not be detected by the classical cell counting method and offer promising
      applications for the environmental detection of microorganisms, either
      engineered, pathogenic, or released for beneficial effects.

PMID- 8285719
TI  - Antimicrobial activity of a newly identified bacteriocin of Bacillus cereus.
AB  - A bacteriocin-producing Bacillus cereus strain was isolated. The bacteriocin,
      here called cerein, was shown to be active specifically against other B. cereus
      strains and inactive against all other bacterial species tested. Cerein was
      detected in the culture supernatants of stationary-phase cells, and its
      appearance was inhibited by induction of sporulation. The bacterial activity of
      cerein was insensitive to organic solvents and nonproteolytic enzymes, partially
      stable to heat, and active over a wide range of pH values. Direct detection of
      antimicrobial activity on sodium dodecyl sulfate-polyacrylamide gel suggested an
      apparent molecular mass of about 9 kDa.

PMID- 8285720
TI  - Streptomyces subtilisin inhibitor-like proteins are distributed widely in
      streptomycetes.
AB  - Streptomyces subtilisin inhibitor-like proteins were found to be distributed
      widely in streptomycetes by using the combination of the convenient, newly
      developed plate assay system and an established liquid culture assay. Almost all
      the strains formerly categorized as Streptoverticillium species produced proteins
      that exhibited inhibitory activity against both subtilisin BPN' and trypsin. N
      terminal regions of three purified proteins showed high structural similarity to
      those of other previously reported SIL inhibitors.

PMID- 8285721
TI  - Rapid glutamate decarboxylase assay for detection of Escherichia coli.
AB  - A rapid test procedure for the enzyme glutamate decarboxylase was developed for
      detection of Escherichia coli. The assay procedure was able to confirm the
      presence of E. coli in enteric broth cultures with 95% specificity for both pure
      cultures and environmental samples. The procedure was capable of detecting
      survivors among chlorine-exposed cells.

PMID- 8285722
TI  - Isolation and characterization of Listeria monocytogenes-specific nucleotide
      sequences.
AB  - Subtracter probe hybridization was used to screen a partial genomic library of a
      clinical isolate of Listeria monocytogenes. Three clones that hybridized with
      genomic DNA from 174 strains of L. monocytogenes but not with genomic DNA from 32
      strains representing other Listeria spp. were recovered. These data establish the
      utility of subtracter probe hybridization for recovering L. monocytogenes
      specific sequences.

PMID- 8285723
TI  - Common soybean inoculant strains in Brazil are members of Bradyrhizobium elkanii.
AB  - The Brazilian inoculant strains 29W and 587 were found to be members of
      Bradyrhizobium elkanii primarily on the basis of 16S rRNA gene sequences
      identical to that of B. elkanii USDA76 and on the basis of reactivity with
      antibodies against serogroups 76 and 31, respectively. The agronomic consequences
      of using strains of B. elkanii as soybean inoculants are discussed.

PMID- 8285724
TI  - Virus inactivation by copper or iron ions alone and in the presence of peroxide.
AB  - Cupric and ferric ions were able to inactivate five enveloped or nonenveloped,
      single- or double-stranded DNA or RNA viruses. The virucidal effect of these
      metals was enhanced by the addition of peroxide, particularly for copper(II).
      Under the conditions of our test, mixtures of copper(II) ions and peroxide were
      more efficient than glutaraldehyde in inactivating phi X174, T7, phi 6, Junin,
      and herpes simplex viruses. The substances described here should be able to
      inactivate most, if not all, viruses that have been found contaminating medical
      devices.

PMID- 8285725
TI  - Annular scaly plaques in an infant. Neonatal lupus erythematosus (NLE).

PMID- 8285726
TI  - Crusted scalp nodule in an infant. Chronic granulomatous disease of childhood
      (CGD).

PMID- 8285727
TI  - Lichenoid papular eruption in a child. Frictional lichenoid dermatitis of
      childhood (FLDC).

PMID- 8285728
TI  - Vesicles and bulla in an infant. Bullous varicella (chicken pox complicated by
      bullous impetigo).

PMID- 8285729
TI  - You say potato, we say potatoe.

PMID- 8285730
TI  - Dermatitis of the leg following saphenous venectomy.

PMID- 8285731
TI  - Abnormal T-cell response in toxic epidermal necrolysis.

PMID- 8285732
TI  - Turban ear.

PMID- 8285733
TI  - Hypereosinophilia secondary to immunodysregulation in patients with HIV-1
      disease.

PMID- 8285734
TI  - Over-the-counter clobetasol propionate.

PMID- 8285735
TI  - Association of asymmetrical facial photodamage with automobile driving.

PMID- 8285736
TI  - Candidiasis endocrinopathy syndrome. Treatment with itraconazole.

PMID- 8285737
TI  - The use of Food and Drug Administration--approved medications for unlabeled (off
      label) uses. The legal and ethical implications.
AB  - Physicians increasingly use Food and Drug Administration (FDA)-approved drugs
      (medication) for unlabeled (off-label) indications. The ethical and legal
      implications of these actions are not always clear. In this article, I examine
      the common law and federal statutory regulations concerning this issue and also
      explore some of the ethical and financial issues involved.

PMID- 8285738
TI  - Fibrogenic growth factors in the eosinophilia-myalgia syndrome and the toxic oil
      syndrome.
AB  - BACKGROUND AND DESIGN: We sought to determine if growth factors of potential
      pathogenetic significance are deposited in the skin, muscle, and peripheral nerve
      lesions of eosinophilia-myalgia (EMS) and toxic oil syndrome. Immunohistochemical
      studies using affinity-purified peroxidase-conjugated antibodies to detect
      transforming growth factor-beta, platelet-derived growth factorAA and growth
      factorBB, fibroblast growth factor, epidermal growth factor, and interleukin 4
      were performed on formalin-fixed, paraffin-embedded specimens. Seven skin biopsy
      specimens from EMS, six skin biopsy specimens from toxic oil syndrome, nine
      muscle biopsy specimens from EMS, and one sural nerve biopsy specimen from EMS
      were studied. RESULTS: Growth factor staining was noted primarily in the
      epidermis and periappendageal locations of the dermis. The presence of TGF-beta
      and platelet-derived growth factorAA in the periappendageal dermis was
      significantly more prevalent in EMS than toxic oil syndrome (57% vs 0%).
      Prominent staining of transforming growth factor-beta was also present in the
      perimysial connective tissue of five (63%) of eight EMS muscle biopsy specimens
      and one sural nerve biopsy specimen. CONCLUSIONS: These studies implicate
      transforming growth factor-beta and platelet-derived growth factorAA as
      potentially important cytokines in EMS and suggest that the pathogenesis of
      tissue fibrosis in EMS and toxic oil syndrome may be dependent on different
      growth factors.

PMID- 8285739
TI  - Talc deposition in skin and tissues surrounding silicone gel-containing
      prosthetic devices.
AB  - BACKGROUND AND DESIGN: Periprosthetic capsule formation is the most common cause
      of morbidity associated with silicone gel-filled breast implants. All implant
      recipients develop capsules. However, the extent of capsule formation varies
      greatly among patients, ranging from a thin flexible membrane to a constrictive
      inelastic band of sclerotic collagen. Although silicone gel bleed has been
      proposed as the most likely cause of excessive capsular sclerosis, liquid
      silicone did not induce fibrosis in early clinical trials. Because many implant
      modifications have been introduced since the original studies were performed, a
      more plausible explanation for excess capsular sclerosis is the inadvertent
      introduction of a fibrogenic contaminant. The skin and periprosthetic tissues
      removed from 41 women during implant revision surgery were examined for the
      presence of foreign substances that might contribute to capsular sclerosis.
      Tissue was examined histologically with and without polarizing filters and with
      scanning electron microscopy equipped for energy-dispersive x-ray analysis.
      RESULTS: A high incidence of talc was found within the skin and tissues adjacent
      to silicone-containing breast prostheses. Birefringent talc crystals, identified
      in 71% of the patients, were observed within nodular granulomas and perivascular
      histiocytes. Two specimens containing talc crystals were analyzed by energy
      dispersive roentgenographic analysis, which confirmed the identity of the
      crystalline material as talc. Among 10 capsules examined by direct
      immunofluorescence, there was no evidence of immune complex deposition.
      CONCLUSIONS: The high incidence of talc deposition in the skin and tissues
      surrounding silicone implants suggests that talc either is introduced at the time
      of implant surgery (possibly in association with the silicone elastomer bag,
      tissue sizers, or surgical gloves) or is released into the tissues as a silicone
      gel contaminant during gel bleed. Talc, a known sclerosing agent, may contribute
      to periprosthetic fibrosclerosis.

PMID- 8285740
TI  - Histopathologic findings in cutaneous lupus erythematosus.
AB  - BACKGROUND AND DESIGN: The possible distinction between different types of
      cutaneous lupus erythematosus (CLE) based on histologic features has been largely
      debated. This study describes the histopathologic features of three distinct
      subsets of CLE: chronic, annular-subacute, and papulosquamous-subacute. Biopsy
      specimens from 92 patients with CLE were examined without the clinical diagnosis
      being known by the examiners. Of them, 36 clinically demonstrated chronic CLE;
      32, annular-subacute CLE; and 24, papulosquamous-subacute CLE. RESULTS: In
      chronic CLE, the dermal changes (basement membrane thickening, dermal colloid
      bodies, pilosebaceous atrophy, and periappendageal infiltrate) were more
      frequent, while in annular-subacute CLE, a more severe vacuolation of the basal
      layer and a greater number of epidermal colloid bodies were seen. In addition,
      pilosebaceous atrophy and more severe epidermal damage were almost exclusive to
      chronic CLE and annular-subacute CLE, respectively. CONCLUSIONS: Although some
      histologic differences between chronic and annular-subacute CLE exist,
      histopathologic diagnosis of the CLE subsets can only be accurately established
      when pilosebaceous atrophy or necrosis of all epidermal layers is observed.

PMID- 8285741
TI  - Cutaneous manifestations and histologic findings in the hyperimmunoglobulinemia D
      syndrome. International Hyper IgD Study Group.
AB  - BACKGROUND AND DESIGN: The hyperimmunoglobulinemia D (hyper-IgD) syndrome is
      characterized by recurrent febrile attacks with abdominal distress, headache, and
      arthralgias. Physical examination reveals cervical lymphadenopathy in most cases
      and, sometimes, splenomegaly. Skin lesions have been observed in isolated cases
      during attacks. We summarize the features of skin lesions and the histopathologic
      findings in biopsy specimens in the hyper-IgD syndrome. RESULTS: A total of 44
      patients with the hyper-IgD syndrome were studied. Thirty-five (79%) of them, 19
      males and 16 females, had skin lesions during febrile attacks. Erythematous
      macules were the most common cutaneous manifestation (15 cases), followed by
      erythematous papules (12 cases); urticarial lesions (nine cases) and erythematous
      nodules (seven cases). Skin biopsy specimens of 10 patients with the hyper-IgD
      syndrome were available for review. The findings varied considerably. Most biopsy
      specimens showed mild features of vasculitis. Nonspecific findings were noted in
      five biopsy specimens; Sweet-like features in two, cellulitis-like findings in
      one, and deep vasculitis characteristics in one. CONCLUSIONS: Skin lesions are
      common in the hyper-IgD syndrome suggesting that they are a true manifestation of
      the disease.

PMID- 8285742
TI  - Thalidomide neuropathy incidence and clinico-electrophysiologic findings in 42
      patients.
AB  - BACKGROUND AND DESIGN: Thalidomide therapy was shown to be effective in numerous
      dermatologic diseases. As reliable methods of contraception are now available,
      neurotoxicity has become the most important side effect limiting the use of
      thalidomide. The incidence of this neuropathy and its relationship to thalidomide
      doses are still matters of debate. In a retrospective study, we reviewed the
      files of 42 patients who had received thalidomide between 1987 and 1992 for
      various dermatologic diseases. The incidence and the conditions of occurrence of
      the neuropathy were analyzed. RESULTS: Evidence of a thalidomide-induced
      neuropathy was present in nine patients (21%), who had both clinical and
      electrophysiologic typical abnormalities. Twelve other patients (28%), however,
      presented with isolated clinical or electrophysiologic signs. Thus, the diagnosis
      of thalidomide neuropathy could not be affirmed. The occurrence of the neuropathy
      did not appear to be related to the daily dose nor to the duration of treatment.
      The highest risk of developing a thalidomide neuropathy was found in female and
      elderly patients. Two monozygotic twin sisters, who received thalidomide for
      Behcet's disease, both developed a neuropathy. CONCLUSIONS: These data suggest
      that the incidence of thalidomide neuropathy may be between 21% and 50%.
      Individual susceptibilities with possible genetic predisposition seem to be more
      important than daily dose and duration of thalidomide therapy.

PMID- 8285743
TI  - Lichenoid chronic graft-vs-host disease occurring in a dermatomal distribution.
AB  - BACKGROUND: Chronic graft-vs-host disease (GVHD) is a late complication of
      allogeneic bone marrow transplantation and is associated with high morbidity and
      mortality. While the pathogenesis of chronic GVHD is not fully understood,
      several observations and studies suggest that viral infections may play a role.
      We describe two patients who developed linear lichenoid chronic GVHD. The
      dermatomal distribution of their lesions suggests an association with herpes
      zoster virus infection. OBSERVATIONS: Two allogeneic bone marrow transplantation
      patients developed violaceous papules in a dermatomal distribution. Histologic
      examination of these lesions revealed dyskeratosis, vacuolar changes in the basal
      layer, and a mild perivascular and interstitial infiltrate, diagnostic of
      lichenoid chronic GVHD. CONCLUSIONS: The linear distribution of our patients'
      lichenoid chronic GVHD is unique and may represent an association with herpes
      zoster virus infection, providing further support for a role for viral infections
      in the pathogenesis of chronic GVHD.

PMID- 8285744
TI  - Lichen planus and hepatitis C virus--related chronic active hepatitis.
AB  - BACKGROUND AND DESIGN: An increased prevalence of chronic liver disease has been
      reported in patients with lichen planus (LP). We report six cases of LP
      associated with chronic active hepatitis and actively replicating hepatitis C
      virus (HCV). RESULTS: We studied six patients (three men and three women; mean
      age, 61 years; age range, 47 to 70 years) with various forms (cutaneous and/or
      mucosal) of LP and abnormal liver test results. Four patients had severe mucosal
      lesions. Cutaneous and mucosal lesions had a long-term evolution. Liver disease
      was discovered 2 to 6 years before LP in three cases and was diagnosed at the
      same time as LP in the three other cases. Liver biopsy performed in five patients
      showed chronic active hepatitis without cirrhosis in all five cases. Anti-HCV
      antibodies were detected in all cases by second-generation enzyme-linked
      immunosorbent assay and confirmed by second-generation recombinant immunoblot
      assay. Hepatitis C virus RNA was evidenced by means of polymerase chain reaction
      in the serum samples from the six patients, proving active viral replication.
      CONCLUSIONS: Lichen planus may be associated with HCV-related chronic active
      hepatitis. As interferon treatment may induce viral inactivation in some patients
      with HCV-related chronic liver disease, a search for HCV infection should be
      systematically performed in patients with chronic LP.

PMID- 8285745
TI  - Aging and photoaging affect gene expression in cultured human keratinocytes.
AB  - BACKGROUND: Aging has two components: changes that occur in all individuals with
      the passage of time alone and changes that occur to varying degrees in different
      individuals as a result of repeated environmental injury. In the skin, the major
      environmental influence is sun exposure, and the combined effect of aging and sun
      damage has been termed photoaging. To determine whether aging and photoaging have
      characteristic effects on gene expression, we performed Northern blot analysis of
      several genes in early-passage cultured keratinocytes derived from donors of
      different ages (newborn, young adult, and old adult) and from paired sun-exposed
      (photoaged) and sun-protected sites of old-adult donors. OBSERVATIONS: We
      examined genes involved in cell division, immunomodulation, or differentiation.
      Aging alone strikingly increased the baseline expression of the differentiation
      associated SPR2 and interleukin 1 receptor antagonist (IL-1ra) genes but had
      relatively little effect on the UV inducibility of any genes studied. In
      contrast, photoaging markedly increased the inducibility of the c-fos proto
      oncogene and decreased the baseline expression of SPR2 and IL-1ra relative to
      that in cells derived from sun-protected skin of the same donors. CONCLUSIONS:
      Both aging and photoaging alter the expression of selected genes that are
      implicated in growth, differentiation, immunomodulation, and UV response in human
      epidermis. This may explain, in part, the predisposition to photocarcinogenesis
      in chronically sun-exposed skin of older individuals.

PMID- 8285746
TI  - The cellular and molecular biology of skin aging.
AB  - BACKGROUND: The dramatic alterations in the appearance of the integument with
      increasing age are due in part to a progressive destruction of the delicate
      architecture of the connective tissue components of the dermis. Both collagenous
      and elastic components display a degeneration consistent with the overexpression
      of proteolytic activity. Recent advances in the field of molecular gerontology,
      using in vitro models of cellular aging, are yielding clues as to the fundamental
      causes of dermal aging. OBSERVATIONS: Dermal fibroblasts possess a finite
      replicative capacity of 50 to 100 doublings, then cease replicating in response
      to growth factors. Cells cultivated to the end of their replicative lifespan in
      vitro display alterations consistent with their playing a role in aging in vivo.
      In particular, senescent dermal fibroblasts overexpress metalloproteinase
      activities that may explain the age-related atrophy of extracellular matrix
      architecture. CONCLUSIONS: The recent discovery of a structural change in the
      telomeric region of the genome with cellular aging and new insights into DNA
      damage checkpoint mechanisms offer new opportunities to uncover both the
      molecular mechanisms regulating cellular aging and possibly to devise new
      strategies to manipulate these molecular events for therapeutic effect.

PMID- 8285747
TI  - Chemical exposure-induced cutaneous fibrosis. Lessons from 'experiments of
      nature'.

PMID- 8285748
TI  - Low cost technology for the newborn in developing countries.

PMID- 8285749
TI  - Randomised trial of routine versus selective paralysis during ventilation for
      neonatal respiratory distress syndrome.
AB  - The strategy of non-selective neuromuscular paralysis was compared with that of
      synchronised (fast rate) ventilation and selective paralysis in infants receiving
      mechanical ventilation for respiratory distress syndrome with chronic lung
      disease as the primary outcome measure. One hundred and ninety three infants
      weighing under 2000 g were randomly allocated to receive either pancuronium
      during mechanical ventilation in the acute phase of respiratory distress syndrome
      (non-selective group) or synchronised ventilation (initial ventilatory rate at or
      above that of the infant's) (selective group). Infants in the selective group
      received pancuronium if they were consistently expiring during the inspiratory
      phase of the ventilator cycle. There was no significant difference between the
      groups with respect to birth weight, gestation, and sex distribution. There was
      no significant difference between the group with respect to death (selective 19%,
      non-selective 16%), pneumothorax (selective 14%, non-selective 14%), chronic lung
      disease (selective 49%), non-selective 47%), and oxygen dependency at 36 weeks'
      postmenstrual age (selective 32%, non-selective 39%). Routine paralysis of
      ventilated infants has potential complications that may be avoided by using
      synchronised ventilation. As the latter is not associated with an increased
      incidence of long term respiratory complications, it is concluded that it is the
      optimum strategy of the two for ventilating infants with respiratory distress
      syndrome.

PMID- 8285750
TI  - Enteral feeding of premature infants with Lactobacillus GG.
AB  - The objectives of this study were to determine whether or not the probiotic
      Lactobacillus GG can colonise the immature bowel of premature infants and if so,
      does colonisation result in a reduction of the size of the bowel reservoir of
      nosocomial pathogens such as enterobacteriaceae, enterococci, yeasts or
      staphylococci, and does colonisation with Lactobacillus GG have any effect on the
      clinical progress and outcome. Twenty preterm infants with a gestational age of
      33 weeks or less who were resident on a neonatal unit were studied from the
      initiation of milk feeds until discharge. The infants were randomised to receive
      either milk feeds or milk feeds supplemented with Lactobacillus GG 10(8) colony
      forming units twice a day for two weeks. The clinical features of the two groups
      of infants were similar. Orally administered Lactobacillus GG was well tolerated
      and did colonise the bowel of premature infants. However, colonisation with
      Lactobacillus GG did not reduce the faecal reservoir of potential pathogens and
      there was no evidence that colonisation had any positive clinical benefit for
      this particular group of infants.

PMID- 8285751
TI  - Effects of feeding premature infants with Lactobacillus GG on gut fermentation.
AB  - The study aimed to find out whether gut colonisation of premature babies with a
      probiotic, Lactobacillus GG, modified enteric carbohydrate fermentation. Twenty
      preterm infants were randomised to receive Lactobacillus GG 10(8) colony forming
      units twice a day for two weeks or to a control group. Faecal short chain fatty
      acids (SCFAs), ethanol, and urinary 2,3-butanediol, were measured in parallel
      with microbiological studies. Lactobacillus GG colonised nine babies. From 1-28
      days of age faecal SCFAs did not differ significantly from controls. Median and
      ranges were (treated and controls, respectively): acetic acid: 173 (trace-799),
      166 (trace-700); propionic acid: 44 (trace-169), 37 (11-229); butyric acid: 31 (5
      107), 37 (2-118) mumol/g dry weight. Ethanol was detected in more faecal samples
      from treated babies (65% v 37%), and at higher concentration (6.3 (trace-40) v
      3.3 (0.6-8.8; one 229) mumol/g). 2,3-Butanediol was found in 66% of urine samples
      from treated babies and 58% from controls. On 83% of these occasions Klebsiella
      sp, Enterobacter sp, or Serratia sp were cultured from faeces. Lactobacillus GG
      had no obvious adverse effects on nutritionally important SCFAs. The small
      increase in ethanol excretion is unlikely to have clinical significance.

PMID- 8285752
TI  - Non-invasive measurement of intracranial pressure in the newborn and the infant:
      the Rotterdam teletransducer.
AB  - Knowledge of intracranial pressure may be important in many clinical situations
      in neonates and young infants. The best way to obtain this information would be a
      non-traumatic procedure. In order to test the reliability of a new fontanometer,
      the Rotterdam teletransducer, 25 simultaneous measurements of cerebrospinal fluid
      (CSF) pressure and anterior fontanelle pressure (AFP) were performed. Mean (SD)
      difference between CSF pressure and AFP was -0.2 (1.8) mm Hg (95% confidence
      interval from -0.48 to -0.88 mm Hg). The AFP was also measured in 60 healthy
      children (15 premature, 30 term newborn babies, and 15 infants). The different
      aspects of AFP were analysed and normal values computed. These results suggest
      that the Rotterdam teletransducer gives reliable continuous information about
      intracranial pressure and can be used in clinical practice. Interpretation of AFP
      plots must take the influence of postconceptional age and the physiological
      occurrence of pressure waves into account.

PMID- 8285753
TI  - Knemometry and the assessment of growth in premature babies.
AB  - The characteristics of a knemometer designed for accurate lower leg measurement
      in babies were assessed. Repeated measurement of a 100 mm Perspex rod gave a mean
      length of 99.993 mm and a mean SD of 0.058. When used to measure leg length,
      technical error of the measurement technique was 0.31 with a mean leg length of
      98.49 mm (coefficient of variation 0.31%). Leg lengths measured at birth in 324
      babies from 23 to 42 weeks' gestation gave an estimated in utero leg length
      velocity of 0.43 mm/day (95% confidence interval 0.41 to 0.45). Assessment of
      interobserver variation showed poor agreement in absolute values of leg length,
      although similar estimates of leg length velocity could be obtained. The neonatal
      knemometer allows measurements to be made in situations where conventional growth
      measurements are not possible. It is believed that knemometry has an important
      role in accurate evaluation of factors that can influence short term bone growth.

PMID- 8285754
TI  - Growth retardation after dexamethasone administration: assessment by knemometry.
AB  - Knemometry has been used to measure lower leg growth during 32 nine day courses
      of dexamethasone in 26 babies ranging from 24 to 32 weeks' gestation at birth.
      Mean leg length velocity was 0.37 mm/day in the 10 days before steroids.
      Administration of dexamethasone was associated with a decrease in velocity in all
      babies, and in 15 leg shortening was documented. Mean leg length velocity during
      steroid treatment was -0.003 mm/day. After the course of dexamethasone was
      completed there was an immediate increase in leg length velocity to a mean of
      0.52 mm/day over the first 10 days then falling to a value similar to the growth
      velocity observed before treatment. Leg length had reached the value predicted by
      growth before steroids about 30 days after dexamethasone. The reduction in leg
      length velocity occurred despite a significant increase in energy intake and
      decrease in oxygen requirements.

PMID- 8285755
TI  - Fetal echogenic gut: a marker of intrauterine gut ischaemia?
AB  - The pathophysiological significance of fetal echogenic gut (FEG) is unknown. Our
      aim was prospectively to evaluate FEG in infants with intrauterine growth
      retardation (IUGR) and absent umbilical artery end diastolic flow velocities.
      Over a 15 month period, nine infants with FEG met these criteria. Nine infants
      who, on antenatal assessment, had demonstrated IURG and absent umbilical artery
      end diastolic flow velocities, but no evidence of FEG, were selected as case
      controls. Gastrointestinal function was then prospectively evaluated in both
      groups after delivery. All liveborn infants received nasogastric feeds of breast
      milk by 8 days of age. All in the FEG group developed marked abdominal
      distension, large, bile stained, nasogastric aspirates, and constipation
      requiring rectal washouts. This led to a discontinuation of enteral feeds on one
      or more occasions. Two patients in the FEG group required water soluble contrast
      enemas in order to relieve intestinal obstruction. In the control group, 3/9
      patients had abdominal distension, but no rectal washouts were given and enteral
      feeds were not interrupted. The median (range) time to tolerate full enteral
      feeds was 15 (7-32) days in the FEG group, compared with 4 (1-8) days in the
      control group. In the FEG group 5/6 patients required parenteral nutrition for 5
      27 days. In the control group one patient required parenteral nutrition over a
      period of four days only. No child had necrotising enterocolitis or cystic
      fibrosis. When FEG is observed in the fetus with IUGR, problems with enteral
      feeding should be anticipated.

PMID- 8285756
TI  - Inhaled nitric oxide for pulmonary hypertension after repair of exomphalos.
AB  - Inhaled nitric oxide was used successfully to treat a newborn infant with severe
      pulmonary hypertension complicating repair of congenital exomphalos. The infant
      had failed conventional treatment and extracorporeal membrane oxygenation was
      unsuitable because of the risk of bleeding from the recent laparotomy. Extended
      treatment with inhaled nitric oxide appears safe and may offer an alternative to
      mechanical life support in severe cases of neonatal pulmonary hypertension.

PMID- 8285757
TI  - Systolic blood pressure and blood volume in preterm infants.
AB  - Blood volume and systolic blood pressure (SBP) were measured in 43 preterm
      infants. Mean (SD) blood volume was 83 (19) ml/kg (range 48-119) and SBP 50 (9)
      mm Hg (range 34-69), showing a significant overall relationship. Blood volume in
      infants with SBP > 60 mm Hg (110 (6) ml/kg) was significantly higher than in
      infants with SBP 40-60 mm Hg (78 (16) ml/kg) and in infants with SBP < 40 mm Hg
      (75 (10) ml/kg). In conclusion, SBP is of limited value in detecting hypovolaemia
      in very low birthweight infants.

PMID- 8285758
TI  - Fetal anaemia due to pyruvate kinase deficiency.
AB  - Pyruvate kinase deficiency was diagnosed in an infant by umbilical vessel
      sampling at 30 weeks' gestation. Although three previous hydropic siblings had
      been stillborn or died in the neonatal period, this infant survived with
      transfusion dependent haemolytic anaemia. Prompt fetal diagnosis of pyruvate
      kinase deficiency is feasible and allows better management of hydrops fetalis due
      to this disorder.

PMID- 8285759
TI  - Bronchocutaneous fistula associated with mechanical ventilation.

PMID- 8285760
TI  - Symptomatic congenital cytomegalovirus infection in two consecutive sisters.
AB  - The occurrence of symptomatic congenital cytomegalovirus (CMV) infection in two
      consecutive sisters is reported. The first sibling showed hepatosplenomegaly with
      slight hyperbilirubinaemia and abnormal liver function tests, right inguinal
      hernia, and peripheral lymphoedema. Her sister, the product of an uneventful
      pregnancy showing no signs of CMV reactivation, had life threatening CMV disease,
      including microcephaly, hepatitis with high serum bilirubin concentrations, and
      thrombocytopenic purpura.

PMID- 8285761
TI  - Patent ductus arteriosus in the newborn.

PMID- 8285762
TI  - Therapeutic bronchoscopy in ventilated neonates.

PMID- 8285763
TI  - Training overseas graduates in neonatal intensive care.

PMID- 8285764
TI  - Hippocrates (460-c 356 BC) and the founding of perinatal medicine.

PMID- 8285765
TI  - Double blind trial of recombinant human erythropoietin in preterm infants.

PMID- 8285766
TI  - Should we look after babies less than 800g?

PMID- 8285767
TI  - When will my baby go home?

PMID- 8285768
TI  - Bilateral congenital diaphragmatic hernia--delayed presentation of the
      contralateral defect.

PMID- 8285769
TI  - Ranitidine in infants.

PMID- 8285770
TI  - Stereotactic techniques for brain biopsies.

PMID- 8285771
TI  - Regional anaesthesia for surgical treatment of inguinal hernia in preterm babies.

PMID- 8285772
TI  - Follow up of victims of fabricated illness (Munchausen syndrome by proxy).
AB  - Fifty four children were studied 1-14 (mean 5.6) years after fabrications of
      illness had been identified. Thirty of the 54 children were living in families
      with their biological mothers and 24 were with other family members or in
      substitute families. Further fabrications were identified for 10 children who had
      been living with their mothers and there were 'other concerns' for a further
      eight children. Thirteen children residing with mother and 14 not residing with
      mother at follow up had a range of disorders including conduct and emotional
      disorders, and problems related to school, including difficulties in attention
      and concentration and non-attendance. Overall, 20 children (49% of those
      successfully followed up) had outcomes that were considered to be unacceptable.

PMID- 8285773
TI  - Management of Kawasaki disease in the British Isles.
AB  - Kawasaki disease in the British Isles was surveyed by an active reporting scheme,
      based on all cases reported to the British Paediatric Surveillance Unit that were
      diagnosed between 1 January and 31 December 1990. The study was prompted by the
      need to investigate the high case fatality rate of Kawasaki disease of 2%
      observed in 1988. One hundred and sixty three patients were identified of whom
      six (3.7%) died. Forty five children (28%) suffered cardiac complications of
      which 39 (24%) were coronary artery abnormalities; five children were diagnosed
      at postmortem examination, and coronary artery abnormalities were detected by
      echocardiography in 34. One hundred and forty nine children (93%) had
      echocardiography. High thrombocytosis, leucocytosis, duration of fever, and
      younger age were associated with the presence of coronary artery abnormalities.
      Erythrocyte sedimentation rate, sex, and the number of diagnostic criteria were
      not. One hundred and thirty three children (87%) received aspirin. Ninety three
      children (61%) received intravenous gammaglobulin (IVGG). Children were more
      likely to receive IVGG if they had thrombocytosis or typical Kawasaki disease.
      The incidence of coronary artery abnormalities was found to be similar in those
      treated with IVGG (29%) and those untreated (20%), including those treated within
      10 days of onset. This may have reflected selection of the more serious cases to
      receive IVGG or that Kawasaki disease in the British Isles is a different illness
      to that experienced elsewhere. It amy be, however, that IVGG is less effective in
      the treatment of British patients with Kawasaki disease than has been the
      experience in the United States and Japan. These observations emphasise the need
      for a therapeutic trial of treatment modalities for Kawasaki disease in the UK
      and the Republic of Ireland.

PMID- 8285774
TI  - Effect of oral acyclovir against primary and secondary viraemia in incubation
      period of varicella.
AB  - The effect of oral acyclovir (approximately 40 mg/kg daily in four divided doses)
      against primary and secondary viraemia of varicella zoster virus (VZV) was
      examined in 27 children susceptible to VZV who were exposed to the virus in their
      families and their clinical features were compared with those of 19 non-treated
      subjects. The infection was confirmed by a fluorescent antibody to membrane
      antigen assay in 11 (85%) of 13 children who received acyclovir for the first
      seven days after exposure to VZV and in 11 (79%) of 14 who received acyclovir for
      the next seven days. The geometric mean antibody titre of the former group was
      significantly higher than that of the latter group. Varicella developed in 10
      (91%) and was subclinical in one (9%) in the former group, whereas a very mild
      disease occurred in three (27%) and was subclinical in eight (73%) in the latter
      group. The severity of varicella was significantly greater in the former group
      than that in the latter group. On the other hand, all of the control group
      developed typical varicella and their clinical features were more severe than
      those of the acyclovir administered group. These data indicate that oral
      acyclovir more effectively inhibits replication of VZV in secondary viraemia than
      that of the primary viraemia.

PMID- 8285775
TI  - Development of IgG responses to mycobacterial antigens.
AB  - Recent studies link mycobacterial and human heat shock protein antigens with
      autoimmune diseases. Little is known about the development of antibody responses
      to these antigens in children. IgG responses to mycobacterial antigens were
      studied in children living in the UK (an environment low in mycobacteria) who had
      not received BCG vaccination. Age curves of IgG response to sonicates from
      different species of mycobacteria were similar suggesting that the greater part
      of the developing IgG response is to the common antigens shared by all
      mycobacteria. The major part of the IgG response was to carbohydrate antigens:
      lipoarabinomannan is a mycobacterial cell wall carbohydrate and was confirmed as
      a major immunodominant antigen. Infants showed a marked early response to the
      mycobacterial 65 kilodalton (kDa) and 70 kDa heat shock proteins, but not to the
      human 65 kDa heat shock protein. The early IgG response to heat shock proteins
      may reflect cross reactivity to proteins released by a wide variety of bacteria
      (possibly from breakdown in the gut) or recognition of other immunodominant
      antigens with high levels of cross reactivity to self.

PMID- 8285776
TI  - Nebulised racemic adrenaline in the treatment of acute bronchiolitis in infants
      and toddlers.
AB  - The effect of inhaled nebulised racemic adrenaline upon symptoms of acute
      bronchiolitis was investigated in 29 infants and toddlers aged 2-17.5 months by
      transcutaneous oxygen tension (TcPO2), oxygen saturation, transcutaneous carbon
      dioxide tension (TcPCO2), and clinical evaluation in a double blind placebo
      controlled study. Clinical score and TcPO2 improved significantly at 30, 45, and
      60 minutes after inhalation of racemic adrenaline, with an increase in TcPO2 > or
      = 0.5 kPa in 72% of the children < 1 year of age. No significant improvement was
      observed after inhalation of placebo. No significant changes in heart rate or
      TcPCO2 were observed from before to after inhalation, but a small increase in
      mean systolic blood pressure was observed immediately and 45 minutes after
      racemic adrenaline inhalation. This study demonstrates that treatment with
      nebulised racemic adrenaline improved oxygenation and clinical signs in
      hospitalised children aged less than 18 months with bronchiolitis.

PMID- 8285777
TI  - Omeprazole and high dose ranitidine in the treatment of refractory reflux
      oesophagitis.
AB  - Thirty two consecutive patients (age range 6 months-13.4 years) with severe
      reflux oesophagitis were randomised to a therapeutic trial for eight weeks during
      which they received either standard doses of omeprazole (40 mg/day/1.73 m2
      surface area) or high doses of ranitidine (20 mg/kg/day). Twenty five patients
      completed the trial (12 on omeprazole, 13 on ranitidine). At entry and at the end
      of the trial patients underwent symptomatic score assessment, endoscopic and
      histological evaluation of the oesophagus, and simultaneous oesophageal and
      gastric pH measurement; results are given as median (range). Both therapeutic
      regimens were effective in decreasing clinical score (omeprazole before 24.0 (15
      33), after 9.0 (0-18); ranitidine before 19.5 (12-33), after 9.0 (6-12)), in
      improving the histological degree of oesophagitis (omeprazole before 8.0 (6-10),
      after 2.0 (0-60); ranitidine before 8.0 (8-10), after 2.0 (2-6), and in reducing
      oesophageal acid exposure, measured as minutes of reflux at 24 hour pH monitoring
      (omeprazole before 129.4 (84-217), after 44.6 (0.16-128); ranitidine before 207.3
      (66-306), after 58.4 (32-128)) as well as intragastric acidity, measured as
      median intragastric pH (omeprazole before 2.1 (1.0-3.0), after 5.1 (2.2-7.4);
      ranitidine before 1.9 (1.6-4), after 3.4 (2.3-5.3)). Serum gastrin concentration
      was > 150 ng/l in four patients on omeprazole and in three patients on
      ranitidine. It is concluded that in children with refractory reflux oesophagitis
      high doses of ranitidine are comparable with omeprazole for the healing of
      oesophagitis and relief of symptoms; both drugs resulted in efficacious reduction
      of intragastric acidity and intra-oesophageal acid exposure.

PMID- 8285778
TI  - Sleeping position for infants and cot death in The Netherlands 1985-91.
AB  - Until the early 1970s the traditional sleeping position for Dutch infants was not
      prone. After a much publicised lecture in October 1987 on the possible relation
      between sleeping prone and cot death, the fairly new habit of placing infants
      prone is being replaced by more traditional positions. The decrease in the
      prevalence of the prone sleeping position has been documented in six studies.
      Since 1987 the incidence of registered cot deaths has decreased from 1.04/1000
      live births in 1986 to 0.44 in 1991; the real decrease of sudden unexpected death
      in infancy, however, is greater.

PMID- 8285779
TI  - Sociodemographic factors associated with sleeping position and location.
AB  - Recent research has implicated infant sleeping body position and bed sharing as
      risk factors in the sudden infant death syndrome. The sociodemographic
      associations of infant sleeping body position and location were examined in this
      study. This showed that the majority (86.4%) of New Zealand parents now place
      their infants to sleep on their sides. The remainder place their infants supine
      (1.3%), prone (4.8%), or no particular way (7.5%). In the waking position, 57.9%
      were usually found on their sides, 18.2% supine, and 6.1% prone. Infant sleeping
      position showed marked sociodemographic variability. These findings are a marked
      contrast to previous New Zealand studies which showed a reversed pattern, with
      most infants put to sleep prone. There were also highly significant
      sociodemographic differences in the place of sleeping. Overall 12.2% of infants
      shared a bed, with infants of younger less well educated mothers who were of non
      European origin, with a parity of five or more, or unmarried significantly more
      likely to do so. Infants of unemployed and lower socioeconomic group (Elley
      Irving groups 5 and 6) fathers were also more likely to share a parental bed.

PMID- 8285780
TI  - Screening a state middle school for asthma using the free running asthma
      screening test.
AB  - The free running asthma screening test (FRAST) was used to screen children in a
      state middle school during a normal physical education lesson. The test was
      conducted by the teachers with a general practitioner available via a radiopager.
      Of the 249 children attending the school, aged 8-12 years, 237 (95%) were tested.
      Twenty two (9%) children were known to have asthma, of whom 18 were tested.
      Thirty one children had a significant decrease (> 15%) in their peak expiratory
      flow rate (PEFR) after exercise. Six of these children were known to have asthma,
      indicating that their asthma treatment may be suboptimal. A further six children
      assessed clinically had false positive results. The 31 children with significant
      decreases in their PEFR were matched for age and sex with a control group of 30
      children who were considered to have a normal result. Of the control group, one
      child had clinical asthma. In total, 19 (8%) new cases of asthma were identified,
      giving an overall prevalence of asthma in the school of 16%. These results
      indicate that it is feasible to screen schools for asthma using the FRAST.
      Children with undiagnosed asthma can be identified and the control of children
      with known asthma monitored.

PMID- 8285781
TI  - Psychosocial adjustment in preschool children with atopic eczema.
AB  - Atopic eczema is a chronic skin disorder that is most common in early childhood,
      an important stage in the child's social and emotional development. The
      psychiatric adjustment and mother-child attachment in 30 preschool children with
      severe atopic eczema was compared with 20 matched controls. Patients with eczema
      had a significant increase in behaviour symptoms, 7/30 (23%) v 1/20 (5%); with
      significant excess of dependency/clinginess, 15/30 (50%) v 2/20 (10%);
      fearfulness, 12/30 (40%) v 2/20 (10%); and sleep difficulty, 19/30 (63%) v 9/20
      (45%), but there was no significant difference between the two groups in the
      security of attachments, 25/29 (86%) v 14/20 (70%). Significantly fewer mothers
      of children with atopic eczema were in outside employment, 8/29 (27%) v 13/20
      (65%), or felt supported socially, 10/29 (34%) v 13/20 (65%). Significantly more
      of them, 9/30 (30%) v 1/20 (5%), felt particularly stressed in relation to their
      parenting and less efficient in their disciplining of the affected child. In
      spite of this and at variance with earlier reports in the literature, they did
      not display negative attitudes towards their child. On the contrary mothers had a
      positive empathic attitude towards the child, 7/14 (50%) v 2/16 (12%). Child
      behaviour problems, 7/14 (50%) v 2/16 (12%), and maternal distress, 12/14 (85%) v
      5/16 (31%), were significantly more common in the more severely affected
      children. Minor behaviour problems and parenting distress are important features
      of severe atopic eczema in early childhood but atopic eczema does not lead to
      insecurity of the mother-child attachment.

PMID- 8285782
TI  - Paediatric home care in the UK.
AB  - Paediatric home care services in the UK were ascertained in 1991 and 1992.
      Respondents from 209 (97%) UK health districts and boards identified 62 general
      and 124 specialist paediatric home care services by January 1993, 15% having
      opened in the previous year. Of all UK children, 30% lived in a district with a
      general home care service. Five health regions had only specialist services.
      Districts differed widely in the availability of home care for different
      disorders. The home care services were small, general services employing a mean
      (SD) of 2.5 (1.6) whole time equivalent (WTE) nurses, and specialist services 1.3
      (0.8) WTE nurses. Few services were available 24 hours a day. Funding
      arrangements were diverse and some services had difficulties in obtaining
      consumables and equipment for home use. Despite rapid growth there remains
      considerable scope for the development of paediatric home care throughout the UK.

PMID- 8285783
TI  - Ambulatory blood pressure monitoring.
AB  - Ambulatory blood pressure monitoring (ABPM) in adults is proving to be useful.
      The aim of this study was to determine if ABPM is accurate in the lower blood
      pressure range encountered in children and, equally important, whether it is
      acceptable to children. Thirty one children, between the ages of 6 and 18 years,
      were assessed using an ambulatory blood pressure monitor that uses an
      auscultatory method. Blood pressure was measured in the contralateral arm with a
      mercury sphygmomanometer and an oscillometric device at the beginning and end of
      the study for comparison. Over a blood pressure range of 90-130 mm Hg systolic
      and 40-80 mm Hg diastolic, a close agreement was found with the sphygmomanometer;
      the limits of agreement (+/- 2 SD) were 11.6 mm Hg for systolic blood pressure
      and 13.6 mm Hg for diastolic blood pressure. The bias was less than 1.0 mm Hg.
      The ambulatory device was worn by all patients for at least 16 hours with an
      average of 52 recordings per patient. The majority found the device comfortable
      to wear and were not woken from sleep.

PMID- 8285784
TI  - Intra-atrial calcium infusions, growth, and development in end organ resistance
      to vitamin D.
AB  - A five and a half year follow up of a girl with end organ resistant rickets is
      described. After failing to respond to high dose oral alfacalcidol (4
      micrograms/kg/day) and calcium supplements, treatment for one year with
      domiciliary intra-atrial calcium infusions at 2 years of age induced a complete
      remission, which was maintained on subsequent high dose oral calcium supplement.
      Overnight infusions were well tolerated without adverse cardiovascular or renal
      sequelae or ectopic calcification. If the first three years of life are survived,
      the prognosis for a normal life on oral treatment is excellent.

PMID- 8285785
TI  - Asthma and growth.

PMID- 8285786
TI  - Preoperative and postoperative pain control.

PMID- 8285787
TI  - Dietary treatment of renal insufficiency.

PMID- 8285788
TI  - Early presentation of meningococcal disease after media publicity.

PMID- 8285789
TI  - The dangers of soft bedding for infants.

PMID- 8285790
TI  - National follow up of Haemophilus influenzae meningitis.

PMID- 8285792
TI  - High-tech chronic care: addressing the dilemmas.

PMID- 8285791
TI  - Is hearing assessed after bacterial meningitis?

PMID- 8285793
TI  - President's message: ANNA completes first phase of Patient Classification System.

PMID- 8285794
TI  - Bioethics in nephrology: definitions and practices.
AB  - Ethical theory and principles can be applied and adapted for use in health care;
      individuals or groups may be making bioethical decisions regarding patient care
      in a number of settings. The current bioethical debates in the nephrology
      community and for ESRD patients center on issues of patient selection for
      treatment and criteria for the discontinuation of treatment after it has been
      initiated. This article defines bioethical theory and principles and their
      application to these two issues of patient care.

PMID- 8285795
TI  - Ethical issues in caring for patients with renal failure.
AB  - This article reviews a brief history of the origins of dialysis for patients in
      end stage renal disease (ESRD), focusing on the early beginnings in Seattle, and
      identifies ethical issues emerging from the new technology. Current ethical
      issues in ESRD are discussed along with an approach to ethical problem-solving
      that nephrology nurses may find useful in analyzing cases in the clinical
      context.

PMID- 8285796
TI  - A proposal for guidelines for patient acceptance to and withdrawal from dialysis:
      a follow-up to the IOM report.
AB  - The Institute of Medicine Committee for the Study of the Medicare End Stage Renal
      Disease Program recommended that the nephrology community, patients, and families
      develop guidelines for decisions to accept patients to and withdraw them from
      dialysis. This article rebuts the arguments that have been voiced against such
      guidelines, presents arguments for them, and proposes a mechanism for their
      development should general agreement to draft such guidelines be reached.

PMID- 8285797
TI  - Moving beyond the Patient Self-Determination Act: educating patients to be
      autonomous.
AB  - This article explores the limitations of the Patient Self-Determination Act. We
      need to think of advance directives as a process of understanding, reflecting,
      and discussing, not just a written document. Further, health care professionals
      must initiate the process of advance directive education in the outpatient
      setting. Our dialysis unit has successfully integrated this view into daily care
      of patients and families.

PMID- 8285798
TI  - Ethical issues in the elderly ESRD patient.
AB  - The fastest growing population group in the United States is the over 65 years
      old group. In 1985, 59% of all new patients to chronic dialysis were age 55 years
      or older. Quality of life has been a health care issue in the past and is more so
      now with decreasing health care resources. The rationing of health care resources
      has become an increasingly important issue in determining and defining the
      quality of life, especially for the chronically ill elderly. This article does
      not support either dialysis treatment or no dialysis treatment for the elderly,
      but assists readers to consider the implications to the health care system and
      the limited health care resources that are present. This bioethical dilemma will
      be with the health care system for years to come.

PMID- 8285799
TI  - Quality of life of hemodialysis patients.
AB  - The purpose of this study was to assess the quality of life of hemodialysis
      patients. The sample (n = 349) was selected randomly from the adult, inunit
      hemodialysis patient population of 90% of the counties of Illinois, with the
      exception of those dialyzed by the Veterans Administration. The findings indicate
      that the patients in this study were satisfied with their lives in general.
      Nevertheless, the results also indicated that continued efforts are needed to
      improve the health and financial independence of hemodialysis patients.

PMID- 8285800
TI  - Annotated bibliography: general research texts and statistics.

PMID- 8285801
TI  - Maintaining near-normal life style for ESRD patients.
AB  - Over the past 2 years, the nephrology nursing staff assisted the patient to meet
      all four expected outcomes. He has in the past and is currently demonstrating
      positive coping strategies and problem-solving techniques. His hematocrit was
      maintained above 27% whenever possible. He expressed satisfaction with his
      sexuality and is a very proud father. His pretransplant knowledge deficit was
      overcome by the education given by the transplant team and his primary nurse. The
      multidisciplinary team approach was successful in assisting to maintain a near
      normal lifestyle for a most grateful ESRD patient. His cooperative attitude,
      young age, and generally good health allowed him to take an active part in his
      care.

PMID- 8285802
TI  - When caring isn't enough.
AB  - The patient met three of the expected outcomes while receiving hemodialysis. Soon
      after, she became an ethical dilemma and challenge for the nephrology nurses. The
      inconsistent telephone communications left us feeling helpless. The fourth
      outcome seemed to be met during the final days of G.S.'s life. As nurses, we may
      find it difficult caring for patients who make decisions contrary to ours.
      Moreover, when we are not convinced these decisions are made voluntarily and
      willingly, and when our nursing concerns are not received or valued, the ethical
      dilemmas result in overwhelming cognitive and emotional frustration.

PMID- 8285803
TI  - Transmission of HIV in dialysis units.

PMID- 8285804
TI  - Ethical issues in drug pricing.

PMID- 8285805
TI  - Case management of the anemic patient: epoetin alfa--focus on osteitis fibrosa.
AB  - Most patients with anemia caused by end-stage renal disease respond well to
      Epoetin alfa therapy, but in a small number the hematocrit fails to rise as
      expected. A potential cause of suboptimal response is osteitis fibrosa.
      Understanding the pathophysiology, manifestations, diagnosis, and treatment for
      osteitis fibrosa helps nurses to identify this condition as a cause of resistance
      to Epoetin alfa and to manage patients appropriately.

PMID- 8285806
TI  - Patient selection committees: should they be reinstituted?
AB  - Chronic renal failure is no longer synonymous with death. Federal and state
      government funding for end stage renal disease (ESRD) services and advances in
      modern technology now make the prolongation of life possible for almost any
      individual with renal failure. However, the same medical devices and sources of
      funding that support renal replacement therapies have also contributed to the
      moral and ethical debates that surround these treatments. Discussions regarding
      quality of life, rehabilitation statistics, functional status data, prognosis,
      decision making protocol, and selection criteria provoke much controversy in the
      nephrology community and remind us of the "Death or God Committees" utilized in
      the pre-Medicare days to make decisions regarding access to dialysis treatments.
      In this issue of ANNA Journal, Marguerite Hartigan and Christy Price revisit the
      issue of selection criteria and explore the advantages and disadvantages of using
      established protocol to access the services of the ESRD Program and nephrology
      community.

PMID- 8285807
TI  - Chronic sinusitis and the internist. Inadequate training and education.

PMID- 8285808
TI  - Myths of dental-induced endocarditis.
AB  - Although the latest (1990) American Heart Association recommendations for the
      prevention of bacterial endocarditis are by far the simplest yet, many physicians
      and dentists still do not comply with them. One of the reasons for this low
      compliance is that many clinicians rely on "myths" of dental-induced endocarditis
      prevention. To educate clinicians on endocarditis and its prevention, the myths
      of dental-induced endocarditis prevention are analyzed. Myth 1: For the most
      part, physicians and dentists are aware of and comply with American Heart
      Association guidelines on antibiotic prophylaxis for prevention of infective
      endocarditis. Myth 2: Most cases of bacterial endocarditis of oral origin are
      caused by dental procedures. Myth 3: American Heart Association antibiotic
      regimens give almost total protection against endocarditis after dental
      procedures. Myth 4: Antibiotics should be administered for any dental procedure
      that causes bleeding. Myth 5: If a patient was receiving recent antibiotic
      therapy before the dental procedure, there is no need to change the dose or the
      antibiotic before the dental procedure. Myth 6: The risk of endocarditis is
      almost always greater than the risk of antibiotic toxic effects. Myth 7:
      Parenteral antibiotics before dental procedures are preferable for most patients
      with high-risk conditions (eg, prosthetic heart valves and previous history of
      endocarditis). Myth 8: All patients with mitral valve prolapse should routinely
      receive antibiotic prophylaxis for dental procedures. Myth 9: Clinicians should
      err on the positive side of antibiotic prophylaxis to prevent lawsuits.

PMID- 8285809
TI  - Microalbuminuria in non-insulin-dependent diabetes mellitus. Implications for
      renal survival.
AB  - Microvascular and macrovascular disease cause considerable mortality and
      morbidity both among patients with non-insulin-dependent diabetes mellitus and
      those with insulin-dependent diabetes mellitus. Furthermore, non-insulin
      dependent and insulin-dependent diabetes mellitus overlap in their pathogenesis
      as well as short- and long-term complications. In the diabetic patient, genetic
      susceptibility as well as other factors, ie, microalbuminuria, hypertension, high
      protein intake, blood glucose control, etc, ultimately culminate in a diffuse
      disease process, eg, diabetic vascular and/or renal disease. Early predictors of
      susceptibility for development of renal disease in diabetic subjects would help
      focus our treatment strategies. The role of microalbuminuria as a prognostic
      marker for the major complications of insulin-dependent diabetes mellitus has
      been previously reviewed. We reviewed the role of microalbuminuria as prognostic
      marker for progression of diabetic renal disease in subjects with non-insulin
      dependent diabetes mellitus. We examined treatment strategies to lower
      microalbuminuria and its associated impact on disease progression.

PMID- 8285810
TI  - A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs
      in the treatment of arthritis.
AB  - BACKGROUND: To study the relation between reported drug performance in published
      trials and support of the trials by the manufacturer of the drug under
      evaluation, we studied a sample of trials of nonsteroidal anti-inflammatory drugs
      (NSAIDs) used in the treatment of arthritis. METHODS: All randomized control
      trials of NSAIDs published between September 1987 and May 1990 identified by
      MEDLINE were reviewed. If an article met the following criteria (n = 61), it was
      selected: trials involving adult patients with osteoarthritis or rheumatoid
      arthritis (n = 180), use of nonsalicylate NSAIDs marketed in the United States (n
      = 101), randomized control trial (n = 81), duration of the trial 4 or more days
      (n = 78), and use of an efficacy outcome measure (n = 61). Reviewers, "blinded"
      to manufacturer status, evaluated the narrative interpretation of results and
      extracted numeric data on efficacy and toxicity. Manufacturer-associated trials
      were defined as those that acknowledged an association with a pharmaceutical
      manufacturer. Because of the scarcity of non-manufacturer-associated trials (n =
      9), we report only on the manufacturer-associated articles. RESULTS: Fifty-two
      publications (85.2%) representing 56 trials were associated with a manufacturer.
      The manufacturer-associated drug was reported as comparable with (71.4%) or
      superior to (28.6%) the comparison drug in all 56 trials. These narrative claims
      of superiority were usually justified with trial data. Of the trials identifying
      one drug as less toxic (n = 22), the manufacturer-associated drug's safety was
      reported as superior to the comparison drug in 86.4% of cases. Justification for
      the narrative interpretation of the trial findings regarding less toxicity was
      provided in only 12 (54.5%) of 22 trials. CONCLUSION: The manufacturer-associated
      NSAID is almost always reported as being equal or superior in efficacy and
      toxicity to the comparison drug. These claims of superiority, especially in
      regard to side effect profiles, are often not supported by trial data. These data
      raise concerns about selective publication or biased interpretation of results in
      manufacturer-associated trials.

PMID- 8285811
TI  - Acquired risk factors for deep-vein thrombosis in symptomatic outpatients.
AB  - BACKGROUND: Epidemiologic studies on deep-vein thrombosis (DVT) have been mainly
      confined to the inpatient population. The aim of this study was to investigate
      the association between DVT and acquired risk factors in a large cohort of
      outpatients with clinically suspected DVT. METHODS: Consecutive outpatients with
      clinically suspected DVT were enrolled in the study. Before objective testing,
      all patients were interviewed by a trained physician for the presence of risk
      factors for DVT development. Subsequently, the presence or absence of DVT was
      assessed with venography. RESULTS: Approximately 50% of cases of DVT were
      considered to be secondary to a major risk factor (immobilization, trauma, and/or
      recent surgery). Among additional risk factors, only increased age (over 60
      years), male gender, malignant neoplasm, heart failure, systemic lupus
      erythematosus, and arteriopathy were independently associated with the risk of
      acute DVT. CONCLUSION: Major risk factors for venous thromboembolism are a common
      cause of DVT among symptomatic outpatients; therefore, the usefulness of
      extending DVT prophylaxis in the outpatient setting should be tested. The role of
      additional risk factors in the development of DVT needs to be established by
      properly designed studies.

PMID- 8285812
TI  - Smoking cessation and time course of decreased risks of coronary heart disease in
      middle-aged women.
AB  - BACKGROUND: We examined prospectively the relation of time since stopping smoking
      with risk of coronary heart disease in middle-aged women. METHODS: The study was
      based on 12 years' follow-up data (1976 through 1988) from the Nurses' Health
      Study, an ongoing prospective cohort study, in which information on smoking
      habits was updated every 2 years by a mailed questionnaire. The study population
      consisted of 117,006 female registered nurses aged 30 to 55 years in 1976 who
      were free of coronary heart disease, stroke, and cancer at baseline. The outcome
      measure used was incident coronary heart disease, defined as nonfatal myocardial
      infarction plus fatal coronary heart disease. RESULTS: A total of 970 incident
      cases of coronary heart disease (215 among participants who never smoked, 214
      among former smokers, and 541 among current smokers) occurred during 1.37 million
      person-years of follow-up. The multivariate relative risk of total coronary heart
      disease among current smokers compared with participants who never smoked was
      4.23 (95% confidence interval, 3.60 to 4.96). Risk of coronary heart disease was
      highest among smokers who started smoking before the age of 15 years (relative
      risk, 9.25; 95% confidence interval, 5.27 to 16.23). The relative risk among
      former smokers was 1.48 (95% confidence interval, 1.22 to 1.79). On stopping
      smoking, one third of the excess risk of coronary heart disease was eliminated
      within 2 years of cessation. Thereafter, the excess risk returned to the level of
      those who never smoked during the interval 10 to 14 years following cessation.
      CONCLUSION: Women who stop smoking will experience an immediate benefit as well
      as a further longer-term decline in excess risk of coronary heart disease to the
      level of those who never smoked.

PMID- 8285813
TI  - Cancer among Hispanic males in south Florida. Nine years of incidence data.
AB  - BACKGROUND: Dade County (Florida) is the largest county in the United States in
      which a majority of the population is Hispanic. To describe and compare cancer
      incidence among white and black Hispanic and non-Hispanic males in South Florida
      and to identify those sites showing important racial-ethnic differences between
      sub-groups, incidence rates were determined from 9 years of prospective
      population-based cancer surveillance data. METHODS: All incident cancer cases
      diagnosed among male residents of Dade County for the period January 1, 1981,
      through December 31, 1989, were obtained from the statewide tumor registry for
      Florida, the Florida Cancer Data System. Race- and ethnic-specific age
      standardized incidence rates and standardized rate ratios to compare rates among
      racial-ethnic subgroups for each site are presented. RESULTS: Compared with white
      non-Hispanics, white Hispanic males had significantly higher rates of cancers of
      the liver, gallbladder, nasal cavity, penis, and thyroid; acute lymphocytic
      leukemia; and Kaposi's sarcoma. Significantly lower rates were found for cancers
      of the esophagus, stomach, colon, rectum, pancreas, lung, testes, bladder, and
      kidney, and for mesothelioma, melanoma, non-Hodgkin's lymphoma, and chronic
      lymphocytic leukemia. Black Hispanics had significantly lower rates only of
      cancers of the esophagus, lung, and prostate than did black non-Hispanics.
      CONCLUSION: Differences were found in incidence rates by race-ethnicity; while
      incidence rates for most sites among white Hispanic males were lower than among
      white non-Hispanics, higher rates for several sites are of particular concern and
      merit further investigation to determine differences in risk factors and
      exposures.

PMID- 8285814
TI  - The effect of gastric bypass surgery on hypertension in morbidly obese patients.
AB  - BACKGROUND: Hypertension is the most common medical disorder associated with
      obesity. The relationship between dietary weight loss and the reduction of blood
      pressure is well established. However, the effect of gastric bypass surgery on
      blood pressure has not been well studied. METHODS: We evaluated the relationship
      between weight loss and blood pressure in patients with diastolic hypertension
      who had gastric bypass surgery for morbid obesity. Patients were defined as
      hypertensive if taking antihypertensive medication or if both the preoperative
      office and mean hospital diastolic blood pressures were greater than 90 mmHg. Two
      of the authors (J.L.C., M.E.R.), blinded to all postoperative weights, classified
      the follow-up hypertensive status into one of four categories: resolved,
      improved, no change, or worse. The relationship between postoperative changes in
      blood pressure status and mean weight loss, percent excess weight loss, and body
      mass index were examined using a one-way analysis of variance. The relationship
      between postoperative weight loss and blood pressure was assessed in the baseline
      normotensive population using linear regression analysis. RESULTS: There were 45
      patients with diastolic hypertension; 91% were taking an antihypertensive
      medication. The mean follow-up was 39 months. The mean preoperative weight was
      137 kg and the mean weight loss at 1, 12, and 24 months following surgery was 13,
      21, and 45 kg, respectively. Twelve months after surgery, hypertension had
      resolved in 22 patients (54%) and had improved in six patients (15%). These
      findings persisted through 48 months postoperatively. There was a significant
      relationship between the percentage of excess weight lost and improvement of
      hypertension at the 6-month and 12-month follow-up visits. There was also a
      significant relationship between the body mass index and improvement of
      hypertension at the 1-month, 12-month, 24-month, and 48-month follow-up visits.
      In the baseline normotensive patients there was not a significant relationship
      between our weight loss measures and changes in blood pressure. CONCLUSIONS: We
      conclude that postoperative weight loss in patients undergoing gastric bypass
      surgery was associated with resolution or improvement of diastolic hypertension
      in approximately 70% of cases. Resolution or improvement of hypertension occurred
      more often in patients with a lower postoperative body mass index.

PMID- 8285815
TI  - Limitations of serum creatinine level and creatinine clearance as filtration
      markers in cirrhosis.
AB  - BACKGROUND: Several studies carried out in a limited number of patients
      demonstrated a wide range of overestimation of glomerular filtration rate (GFR)
      by serum creatinine level and creatinine clearance (Ccr) in liver disease.
      METHODS: We simultaneously evaluated Ccr, inulin clearance, and predicted GFR
      calculated from serum creatinine level in 56 cirrhotic patients. Inulin clearance
      was considered the gold standard for GFR evaluation. RESULTS: The sensitivity of
      serum creatinine level, predicted GFR, and Ccr in detecting renal failure was
      18.5%, 51%, and 74%, respectively. On the basis of inulin clearance, patients
      were divided into two groups: those with normal GFR (mean, 106 +/- 34 mL/min per
      1.73 m2) (group 1, 29 patients) and those with reduced GFR (mean, 56 +/- 19
      mL/min per 1.73 m2) (group 2, 27 patients). Predicted GFR and Ccr were accurate
      markers of GFR in group 1 patients, while both overestimated GFR by about 50% in
      group 2 patients. An increased tubular secretion of creatinine accounted for the
      disparity between Ccr and inulin clearance in these patients. CONCLUSIONS: Our
      results indicate that renal failure is greatly underestimated on the basis of
      serum creatinine level and Ccr in cirrhotic patients. Clinical implications of
      this observation include excessive dosage of potentially nephrotoxic drugs and
      failure to recognize renal impairment induced by such medical treatments as
      diuretic therapy or paracentesis.

PMID- 8285816
TI  - Advance directives. Stability of patients' treatment choices.
AB  - BACKGROUND: Advance directives are intended to extend patient autonomy into
      periods of mental incompetence. However, for advance directives to fulfill this
      objective, patients' choices must be reasonably consistent over time. Thus, we
      assessed the stability of the advance treatment decisions of patients and members
      of the public. METHODS: In a prospective cohort study of 495 outpatients and 102
      members of the public, we studied the stability of scenario- and treatment
      specific choices. Subjects completed an advance directive, which included four
      illness scenarios with 11 treatment choices in each, as part of a questionnaire.
      A second interview was completed by 296 patients and 78 members of the public
      after 6 to 12 months; 154 patients completed a third interview after a further 6
      to 12 months. We assessed stability by comparing each choice between interviews.
      RESULTS: Stability of choices was moderately high among patients (pooled kappa =
      0.39) and members of the public (pooled kappa = 0.48). Stability improved with
      repeat interview (pooled kappa = 0.47 among patients). Patients who had
      discussions with their physicians showed more improvement (kappa = 0.57) than
      others. Patients had a wide range of personal stability levels (0% to 100%), but
      individuals starting out stable rarely became less so (93% of the patients with
      85% to 100% stability maintained this level of stability on the third interview).
      Hospitalized patients showed no significant difference in stability at the second
      interview, but their stability was not improved at the third interview.
      CONCLUSIONS: Our findings generally support the use of advance directives. Most
      people made moderately stable decisions when using scenario- and treatment
      specific directives, and stability improved after they reviewed the decisions,
      especially among those who had discussions with their physicians. Recent
      hospitalization did not decrease stability, although it appeared to reduce the
      improvement that others achieved with repeat interview. These findings suggest
      that advance directives can be relied on 1 to 2 years after completion to reflect
      a patient's choices.

PMID- 8285817
TI  - Aldicarb poisoning. A case report with prolonged cholinesterase inhibition and
      improvement after pralidoxime therapy.
AB  - Aldicarb is the most potent of the commercially available carbamate pesticides
      and is an unusual source of acute human poisonings. We present the case of a 43
      year-old man exposed to aldicarb who developed severe cholinergic symptoms and
      progressive weakness requiring intubation for 5 days. Both his red blood cell
      cholinesterase and plasma pseudocholinesterase levels were depressed for a
      minimum of 44 hours. He demonstrated neuromuscular improvement concurrent with
      pralidoxime administration. The pertinent medical literature on aldicarb
      poisoning is reviewed.

PMID- 8285818
TI  - Self-induced insulin hypoglycemia in a bodybuilder.

PMID- 8285819
TI  - Cardiopulmonary resuscitation survival.

PMID- 8285820
TI  - A unifying physical diagnosis for Adolph Hitler.

PMID- 8285821
TI  - [Endothelial dysfunction and coronary vasomotricity. Contribution of endocoronary
      echography].
AB  - The regulation of flow and diameter of the coronary arteries depends on many
      factors. In normal subjects, increased coronary flow is associated with an
      increase in diameter of the epicardial coronary vessels. The coupling of these
      two independent variables depends on the integrity of endothelial function. In
      isolated arteries suppression of the endothelium induces an abnormal vasomotor
      response to acetylcholine. The presence of atherosclerotic lesions on the
      coronary vessels also induces the opposite response to the administration of
      acetylcholine, even in apparently normal segments. Other physiological coronary
      vasodilator stimuli, especially those which increase the concentration of
      noradrenaline, become vasoconstrictor in diseased coronary vessels. Finally,
      increasing coronary blood flow is not associated with increases in coronary
      diameter in patients with coronary atherosclerosis. This loss of flow-dependent
      vasodilatation is an early and diffuse phenomenon in subjects with cardiovascular
      risk factors. The authors have shown that this inversion of vasomotor responses
      observed by angiographic techniques, may also be documented by endocoronary
      ultrasonography. Their results demonstrate that the vasodilatation induced by
      papaverine or by the cold pressor test in 6 normal subjects is lost in 20 
      patients with coronary atherosclerosis and that the administration of Sin 1
      induces a comparable vasodilatation in normal and diseased vessels. This study
      confirms that endothelial function is globally altered in atherosclerotic
      coronary artery disease.

PMID- 8285822
TI  - [Detection and prognostic value of silent myocardial ischemia].
AB  - Silent myocardial ischaemia (SMI) is a common manifestation of coronary artery
      disease. Continuous electrocardiographic recordings have shown that 75% of
      ischemic episodes are asymptomatic. In addition, SMI has the same consequences as
      symptomatic ischaemia on myocardial perfusion and ventricular function. There are
      many means of detecting SMI, continuous electrocardiographic monitoring, exercise
      stress testing with or without methods of analysis of myocardial perfusion or
      wall motion using radioactive tracers or echocardiography. The latter techniques
      seem to improve the sensitivity of exercise stress testing. More recently,
      pharmacological stress testing coupled with myocardial scintigraphy or
      echocardiography has been introduced. In coronary patients, the prevalence of SMI
      on Holter monitoring is about 50% in angina and 25% after myocardial infarction.
      The prognostic value of SMI has been the object of much research. In asymptomatic
      patients with documented coronary artery disease, SMI is associated with a
      relative risk of a cardiac event 2 to 3 times greater than that of subjects
      without ischaemia. In angina pectoris, the relative risk of future cardiac events
      is 5.3 times greater, and that of death is 2.3 times greater. These results
      reported with the Holter method have been confirmed by those of exercise stress
      testing with and without coupled imaging techniques. In unstable angina, the
      results are the same: the relative risk of cardiac events in patients with SMI on
      Holter monitoring is increased by a factor of 4.5, and that of death by a factor
      of 4. This increased risk is also observed after myocardial infarction whether
      SMI is recorded by Holter monitoring or exercise stress testing. However, these
      observations are not confirmed in all reports.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285823
TI  - [Myocardial revascularization in silent myocardial ischemia].
AB  - Although there have been many reports of medical treatment of silent myocardial
      ischaemia (SMI) there have been fewer studies on the effects of myocardial
      revascularisation for this form of ischaemia. Myocardial revascularisation by
      coronary bypass surgery is particularly beneficial in patients with triple vessel
      disease and poor ventricular function, as shown by Weiner in a subgroup of
      patients from the CASS study. The tendency nowadays is to offer percutaneous
      transluminal coronary angioplasty (PTCA), because it is less traumatic,
      relatively simple and effective. A review of the literature shows that SMI may be
      treated effectively by PTCA. In a personal series of 62 patients, 80% of those
      are still asymptomatic and have no signs of ischaemia on maximal negative
      exercise stress tests one year after the procedure.

PMID- 8285824
TI  - Clinical trials in silent ischaemia: lessons from TIBET.
AB  - The Total Ischaemic Burden European Trial (TIBET) affords the opportunity to
      investigate the prognostic value of both exercise testing and ambulatory
      monitoring on and off medical treatment; 682 patients were followed for two
      years. Patients with < 1 mm ST segment depression on exercise testing have very
      low risk indeed of an important end point in a two year period, and this effect
      is partially obscured by the presence of medical treatment. Ambulatory monitoring
      showed that the presence of silent ischaemia had little prognostic impact in this
      group of patients.

PMID- 8285825
TI  - Silent ischaemia--to treat or not to treat?
AB  - The authors summarise published data concerning silent myocardial ischaemia: they
      review the studies showing the poor prognosis of this type of myocardial
      ischaemia but pose the question of whether this is due to the severity of the
      lesions causing the ischaemia or to the ischaemia itself. To answer this
      question, it would be necessary to set up a therapeutic trial showing that
      treatment preventing the electrocardiographic changes of silent ischaemia is
      associated with an improved prognosis. In the absence of solid evidence on this
      point, the authors present the case for and against treatment of silent ischaemia
      without drawing any formal conclusions.

PMID- 8285826
TI  - [Therapeutic choices in silent ischemia].
AB  - Silent or painless myocardial ischaemia is a common presentation of coronary
      insufficiency. Repeated episodes lead to anatomical and functional myocardial
      changes and are associated with the risk of ischemic cardiomyopathy, infarction,
      arrhythmias and sudden death. The physiopathology is complex and involves
      transient changes in coronary flow secondary to abnormalities of coronary
      vasomotricity. It is commonly observed in association with symptomatic angina, in
      unstable angina and after acute myocardial infarction. In all cases, appropriate
      treatment is required, the aim being to decrease and suppress not only pain but
      also ischaemia. Treatment is guided by the ischemic episodes. "Isolated" silent
      myocardial ischaemia as the only sign of coronary insufficiency justifies
      accurate evaluation of the coronary status, risk factors and a therapeutic trial,
      followed by systematic coronary angiography if the ischaemia persists. Silent
      myocardial ischaemia has modified classical therapeutic attitudes in which the
      choice of treatment is based on the severity of functional impairment. Priority
      should now be given to treating the severity of the ischaemia and of the
      anatomical lesions.

PMID- 8285827
TI  - Primary lymphoma of the kidney in the acquired immunodeficiency syndrome.

PMID- 8285828
TI  - Primary lymphoma of the kidney.

PMID- 8285829
TI  - Body fluid microscopy in US laboratories. Data from two College of American
      Pathologists surveys, with practice recommendations.
AB  - Questionnaires addressing laboratory practices in cerebrospinal fluid and body
      fluid (serous, synovial) microscopy were distributed to participants in the
      Clinical Microscopy Survey of the College of American Pathologists, Northfield,
      Ill, in 1985 and 1989. In both Surveys, cell enumeration was performed primarily
      by hemocytometry, while nearly all respondents used Wright-stained microscopy.
      There was little formal quality control to assess the accuracy of counts or
      differential cell count. Less than 55% of laboratories used the cytocentrifuge.
      About half of respondents performed a differential cell count on every sample.
      Slides with atypical or malignant cells were usually (> 85%) reviewed by
      physicians without automatic referral to the cytopathology section. Only about
      half of respondents examined every synovial fluid specimen with polarized
      microscopy for crystals. Other than a modest increase in use of the
      cytocentrifuge, the 1989 Survey showed little interval change in practices. In
      1989, there was equal dependence on Wright's and Papanicolaou's stains for an
      infrequent diagnosis of malignancy. The low rate of positives may have related to
      the high prevalence of wedge smears, a suboptimal technique. The Hematology and
      Clinical Microscopy Resource Committee of the College of American Pathologists
      makes recommendations for optimal laboratory handling of body fluid specimens for
      microscopy.

PMID- 8285830
TI  - Practice guidelines for autopsy pathology. Autopsy performance. Autopsy Committee
      of the College of American Pathologists.
AB  - The Autopsy Committee of the College of American Pathologists has prepared this
      guideline in conjunction with representatives of other organizations to assist
      pathologists in the performance of autopsies. The guideline is to be regarded as
      being primarily an educational tool. Application of these recommendations on
      autopsy performance is to be made on the basis of the judgment of the pathologist
      engaged in a specific case.

PMID- 8285831
TI  - Experience of an academic reference laboratory using automation for analysis of
      cystic fibrosis mutations.
AB  - OBJECTIVE: To examine the use of partial automation for molecular analysis of
      cystic fibrosis and to evaluate the diagnostic experience gained. DESIGN: Twenty
      four cystic fibrosis mutations, with cumulative mutation detection of 89% in
      North American whites and of 97% in the Ashkenazim, were tested by multiplex
      amplification and allele-specific oligonucleotide hybridization. SETTING: A
      university-based DNA diagnostic laboratory. SUBJECTS: More than 700 serial
      specimens were analyzed for cystic fibrosis mutations over a 5-month period. The
      study included 377 individuals tested for carrier status, of which 288 had no
      family history for cystic fibrosis; prenatal diagnosis for 17 fetuses at a one in
      four risk and eight pregnancies at lower risk; fetal or parental samples for 33
      pregnancies with fetal ultrasound abnormalities; 40 individuals diagnosed with
      cystic fibrosis; and 87 individuals with a possible diagnosis of the disease.
      RESULTS: Automation has permitted increasing numbers of mutations while
      decreasing personnel time and cost. Mutation testing identified 10 carriers with
      no family history for cystic fibrosis, four couples at a one in four risk, and
      five affected fetuses, one ascertained by abnormal fetal ultrasound. Mutation
      analysis also identified two mutant copies of the gene in 26 of 40 individuals
      with a clinical diagnosis of cystic fibrosis, and in two of 87 patients with
      possible cystic fibrosis. CONCLUSION: This partially automated, direct mutation
      analysis provides DNA diagnostic laboratories with the capacity to process a
      larger number of samples at lower cost with greater sensitivity for mutation
      detection. As pilot screening programs are reported, it is appropriate to
      reevaluate recommendations regarding population-based carrier screening for
      cystic fibrosis.

PMID- 8285832
TI  - Analysis of lower genital tract lesions clinically suspicious for condylomata
      using in situ hybridization and the polymerase chain reaction for the detection
      of human papillomavirus.
AB  - The presence of human papillomavirus was analyzed in 123 biopsy specimens of
      lower genital tract lesions, clinically considered to be condyloma, using both in
      situ hybridization and the polymerase chain reaction. Using standard histologic
      criteria only 22% of the lesions could be diagnosed as condyloma, 17% had
      features suggestive but not diagnostic of condyloma and 61% lacked the histologic
      features of condyloma. Human papillomavirus was detected by in situ hybridization
      in 89% of the lesions with the histologic features of condyloma but in only 3% of
      the biopsy specimens lacking the histologic features of condyloma. Fifty percent
      of lesions that had histologic features suggestive, but not diagnostic for,
      condyloma contained human papillomavirus by in situ hybridization. Using
      polymerase chain reaction similar results were found. This study underscores the
      usefulness of human papillomavirus detection methods for analyzing histologically
      equivocal lesions of the lower genital tract.

PMID- 8285833
TI  - Nonepidermotropic cutaneous lymphomas. A histopathological and immunohistological
      study of 52 cases.
AB  - We report the detailed histological and immunohistological findings in 52 cases
      of nonepidermotropic cutaneous lymphoma, as revealed by cutaneous lesions. The
      patients presented mainly with cutaneous nodules and, more rarely, with
      infiltrated plaques, annular erythema, or erythroderma. The staging procedure
      following the diagnosis revealed lymph node and/or bone marrow involvement in
      half of the cases. Nearly 60% of the nonepidermotropic cutaneous lymphomas were
      of the large-cell type. The reticular dermis was involved in all of the cases,
      and the papillary dermis was involved in only 11 of them. Nonepidermotropic
      cutaneous lymphomas were of the B-cell, T-cell, and non-B-, non-T-cell type in
      38, 13, and 1 case(s), respectively. A monotypic immunoglobulin light chain
      expression was detected in 33 of 35 tested cases of the B-cell lymphomas, and a
      loss of one or several pan-T-cell antigens was observed in all of the cases of
      the T-cell lymphomas. In seven cases (13%), the diagnosis of malignancy was based
      only on these immunohistological criteria. This study shows that
      nonepidermotropic cutaneous lymphomas are B-cell lymphomas in 75% of the cases,
      most often of the large-cell type. It also emphasizes the value of
      immunohistochemistry to firmly establish malignancy when routine light
      microscopical findings are questionable.

PMID- 8285834
TI  - Osseous metaplasia in benign colorectal polyps.
AB  - We report two unique cases of metaplastic ossification occurring within a
      tubulovillous adenoma and a juvenile polyp. In both lesions, well-formed bony
      spicules were present that were adjacent to living epithelial cells. The
      metaplastic bone revealed vimentin positivity and cytokeratin negativity. The
      pathogenesis of osseous metaplasia in colorectal tumors remains unclear, but the
      process seems to have no clinical significance.

PMID- 8285835
TI  - Recurrent plurihormonal bimorphous pituitary adenoma producing growth hormone,
      thyrotropin, and prolactin.
AB  - A 48-year-old man with visual disturbances and subtle features of acromegaly had
      elevated serum thyrotropin (thyroid-stimulating hormone) levels but was
      clinically euthyroid and initially had normal blood growth hormone (GH) levels. A
      computed tomographic scan documented a large pituitary tumor; he underwent
      incomplete transsphenoidal adenomectomy. Postoperative octreotide treatment
      failed to shrink the tumor. Rising GH levels necessitated repeated
      transsphenoidal and, subsequently, frontotemporal resection. By histology, the
      tumor was a chromophobic adenoma. In the first specimen, immunocytochemistry
      localized GH, beta-thyrotropin, and alpha-subunit of glycoprotein hormones in
      adenoma cells. The second specimen also contained prolactin, whereas the third
      contained only GH and beta-thyrotropin. By electron microscopy, the tumor was
      bimorphous, composed of elongated thyrotrophs and densely granulated
      somatotrophs. In tissue culture, the first specimen released GH, thyrotropin, and
      alpha-subunit and smaller quantities of prolactin; the second specimen released
      only GH and alpha-subunit; and the third released GH, thyrotropin, alpha-subunit,
      and prolactin. Incubation with somatorelin (GH-releasing hormone) variably
      stimulated release of all four hormones in the first and third specimens;
      protirelin (thyrotropin-releasing hormone) had no effect. Somatostatin
      consistently inhibited release of all four hormones; inhibition by bromocriptine
      mesylate was variable. The mild degree of clinical and biochemical acromegaly is
      unusual for a large macroadenoma, and the reasons for the absence of
      hyperthyroidism are unclear. These discrepancies may be attributed to retarded
      hormone release and/or synthesis due to suppression by somatostatin in vivo.

PMID- 8285836
TI  - Application of an autopsy report specifically designed for cardiovascular
      diseases.
AB  - After modifying the format and content of the autopsy report traditionally used
      at the Instituto Nacional de Cardiologia of Mexico, Tlalpan, we present the
      results of the new, revised autopsy protocol here. The new autopsy protocol
      (model report) was designed as a "fixed format" to describe the cardiovascular
      diseases observed at our institution, thus pretending to collect more and better
      data, providing useful information, and contributing to better clinicopathologic
      correlations. The comparison between the model and traditional reports
      demonstrated an improvement in the autopsy data collection system--achieving
      better clinicopathologic correlations of the main disease and the cause of death,
      and identifying morphologic alterations that would explain it in more cases. The
      model report was also considered more accessible and useful since it permitted
      the answering of more questions raised by clinicians.

PMID- 8285837
TI  - Drug-related pigmentation of the thyroid associated with papillary carcinoma.
AB  - Black pigmentation of the thyroid attributed to minocycline hydrochloride is
      known, but to our knowledge, pigmentation associated with antidepressants has not
      been reported. We studied four patients with papillary carcinoma associated with
      thyroid pigmentation; two had received minocycline therapy, and two had received
      long-term treatment with antidepressants. The thyroids of patients who had been
      treated with minocycline were black, with pigment primarily in nontumorous
      tissue. The thyroids associated with antidepressant therapy were dark red, with
      pigment in both tumorous and nontumorous tissue. All four cases were positive for
      periodic acid-Schiff, periodic acid-Schiff with diastase predigestion, and
      Schmorl's stains and negative for Prussian blue; the results differed from those
      found with Fontana's technique. Minocycline-related pigmentation appears to imply
      a role for the iodide peroxidase system in the accumulation of pigment, whereas
      pigmentation attributed to intake of antidepressants appears to result from
      lysosomal accumulation of the drug itself.

PMID- 8285838
TI  - Vanished islets with pancreatitis in acute-onset insulin-dependent diabetes
      mellitus in an adult.
AB  - We report an autopsy case of acute-onset insulin-dependent diabetes mellitus,
      type I, that occurred in an adult. The patient died 3 days after the clinical
      onset of diabetes. Hyperglycemia, ketonuria, and hyperamylasemia were observed at
      admission. The pathologic examination of the pancreas showed a markedly decreased
      number of islets, and residual islets were small and shrunken. Diffuse
      inflammatory cell infiltrates, which were found in islets and also in acini, were
      mainly T lymphocytes. Shrunken islets were composed of insulin cells, glucagon
      cells, somatostatin cells, and pancreatic polypeptide cells. A decreased number
      of zymogen granules in acini were prominent [corrected]. This case suggested that
      pan-pancreatitis, destroying whole islets and acini, can initiate insulin
      dependent diabetes mellitus.

PMID- 8285839
TI  - Hepatocellular adenoma in glycogen storage disease type IV.
AB  - The development of hepatocellular adenoma has been recognized in association with
      glycogen storage disease type I and, less often, with glycogen storage disease
      type III, but, to our knowledge, it has not been reported in glycogen storage
      disease type IV. We had the opportunity to study an 11-month-old male infant who
      underwent orthotopic liver transplantation for cirrhosis that developed in the
      setting of glycogen storage disease type IV. A clinically unsuspected
      hepatocellular adenoma was present in the explanted liver. Glycogen storage
      disease type IV should be considered as a potential precursor to the development
      of hepatocellular adenoma. Recognition of this association is important, both in
      terms of the differential diagnosis of tumors that occur in this setting and also
      to anticipate potential complications of this benign neoplasm.

PMID- 8285840
TI  - Insensitivity of actin FS in the detection of nonspecific inhibitors.

PMID- 8285841
TI  - A relationship between specific antiphospholipid autoantibodies in normal human
      and autoimmune serum?

PMID- 8285842
TI  - Mammary cystosarcoma with mature adipose stromal differentiation (lipophyllodes
      tumor) arising in a lipomatous hamartoma.
AB  - This report documents an uncommon variant of benign cystosarcoma phyllodes with
      mature adipose stromal differentiation, for which the term lipophyllodes tumor is
      proposed. Origin of this unusual tumor within a lipomatous hamartoma was
      confirmed by histologic and mammographic observations. The lesion developed in a
      40-year-old woman 2 months post partum, and she remained well after treatment by
      biopsy. Lipophyllodes tumor, which features mature adipose tissue in much of the
      stromal component of a cystosarcoma, should not be mistaken for a malignant
      neoplasm. Complete excision is adequate therapy.

PMID- 8285843
TI  - Hyphalike pseudofungus in a lymph node.
AB  - Mediastinoscopic biopsy specimens of multiple paratracheal lymph nodes in a 66
      year-old man with a history of resected pulmonary carcinoma were submitted for
      histologic evaluation. Structures present in one of these lymph nodes
      superficially resembled branching septate fungal hyphae. Perls' stain
      demonstrated that these structures contained iron, and Gomori's methenamine
      silver stain was negative. The histopathologic features are similar to those of
      the first and only previous case report of such structures.

PMID- 8285844
TI  - Aging and sexual function in men.
AB  - Sexual function, and in particular erectile capacity, declines with age in men.
      The present study attempted to identify possible sensory/neural and autonomic
      factors related to this decline. Data on self-reported sexual activity and
      functioning, as well as erectile response to visual erotic stimulation, were
      gathered from 39 healthy, sexually functional men ranging in age from 21 to 82.
      In addition, four parameters of putative significance to sexual functioning were
      measured: penile electrical and vibrotactile thresholds, pudendal somatosensory
      evoked potentials, penile autonomic response to ischemia, and blood testosterone.
      Results indicated significant age-related decreases in self-reported frequency of
      sexual activity and in erectile response to erotica. Furthermore, penile
      sensitivity, response to penile ischemia, and somatosensory evoked potentials
      showed age-related changes. In contrast, self-reported erectile capacity, ratings
      of overall sex life, and levels of testosterone did not change over age groups.
      These findings suggest that decreasing erectile capacity in aging men may be
      related to decreasing sensory/neural and autonomic functioning, but they also
      indicate that factors other than the frequency of and potency for sexual response
      are important to the overall rating of sex life.

PMID- 8285846
TI  - Sexual arousal in diabetic females: physiological and self-report measures.
AB  - Diabetes mellitus, a major health problem afflicting 500,000 Americans each year,
      is a leading cause of male erectile difficulties. Diabetic women may be
      susceptible to a similar diabetic pathogenesis for sexual problems but
      information about the effect of diabetes on female sexual response is sparse and
      conflicting. Past research has been based upon self-report measures, a
      methodology flawed by susceptibility to response bias. Whether diabetic women
      differed from a matched nondiabetic control group in their physiological as well
      as subjective response to erotic stimulus exposures was investigated. Vaginal
      photoplethysmographic measures of capillary engorgement were taken while subjects
      individually viewed counterbalanced erotic and non-erotic videotape
      presentations. Graphically and statistically analyzed results indicated that
      diabetic women demonstrated significantly less physiological arousal to erotic
      stimuli than controls, whereas their subjective responses were comparable. These
      objective, physiological findings support and extend previous subjectively based
      research which found potential diabetes-related sexual dysfunction in female
      diabetics. The groups did not differ, however, in the reported occurrence of
      sexual difficulties.

PMID- 8285845
TI  - Coming out and AIDS-related high-risk sexual behavior.
AB  - How the withdrawal of social support associated with the coming out of gay men
      influences AIDS-related sexual risk-taking among Flemish (Belgian) gay men is
      analyzed. Recruited via key persons, the 379 gay men in this nonclinical cohort
      completed a lengthy, computerized questionnaire dealing with diverse aspects of
      gay life and culture. Independent variables include demographic characteristics,
      AIDS knowledge, coming-out histories, six social support dimensions, and personal
      resources. The dependent variables were insertive and receptive anal intercourse
      with and without a condom. Stepwise regression explained, respectively, 41.2,
      38.4, 18.4, and 14.2% of the variance. Absence of appraisal (the view that others
      approve of the way one does things or feels about things) led to higher
      frequencies of insertive anal sex (both with and without a condom). The
      experience of emotional conflict lowered the use of condoms by the insertive
      partner in anal intercourse. Disapproval by significant others of being gay also
      led to higher levels of receptive anal intercourse without a condom. Subjects
      with a high belief in mastery had higher frequencies of risk-taking, suggesting
      that the combination of the experience of negative reactions and high mastery
      lead to greater involvement in risky sexual behavior. Findings are interpreted
      within the theoretical framework of the coming-out process and gay identity
      formation.

PMID- 8285847
TI  - Patient-reported erectile dysfunction: a cross-validation study.
AB  - Previous work highlighting a significant correspondence between patient-reported
      sex history information and physiological indices of erectile functioning was
      cross-validated. The matched sample comprised of 46 older male veterans
      presenting with erectile dysfunction, with many experiencing chronic physical
      illnesses. All subjects underwent a comprehensive medical and psychological
      evaluation, followed by 2 consecutive nights of in-hospital Rigiscan diagnostic
      monitoring, to evaluate penile rigidity, tumescence, and duration of erectile
      episodes. Stringent criteria were employed to control for confounding of Rigiscan
      results, with elimination from the study for affective, thought, or sleep
      disorders. Results from the multiple regression analyses showed that patient
      reports of AM erections and erectile quality accounted for significant
      proportions of the variance in the Rigiscan criterion measures, with 3 of the 4
      R2 values falling within the Herzberg criterion for cross-validation. Results
      confirm the diagnostic significance of patient self-report for the population of
      older, chronically ill men who present with impaired erectile functioning.

PMID- 8285848
TI  - Deficient erotic gender differentiation in pedophilia: a follow-up.
AB  - Divided 262 phallometrically diagnosed pedophiles into heterosexual, homosexual,
      and bisexual groups, according to the sex of their victims. Each group was then
      divided into 3 subgroups according to degree of admitting to an erotic preference
      for children. They were compared among each other and with 47 self-professed
      heterosexual and 20 self-professed homosexual male volunteers phallometrically
      diagnosed as having an erotic preference for physically mature partners. The
      comparison was in regard to phallometrically assessed "erotic gender
      differentiation." Results demonstrate that gender differentiation of even the
      fully admitting heterosexual pedophiles was significantly weaker than that of the
      heterosexual controls, and the gender differentiation of the fully admitting
      homosexual pedophiles was significantly weaker than that of both groups of
      controls. Gender differentiation of the nonadmitting heterosexual pedophiles was
      significantly weaker than that of the heterosexual pedophiles who fully admitted
      to their paraphilia. This was demonstrated to be caused by the nonadmitters
      suppression of responses.

PMID- 8285849
TI  - Effects of cyproterone acetate on sexual arousal patterns of pedophiles.
AB  - The antiandrogen treatment of sexual offenders has been shown to reduce the
      recidivism rate. The mechanism of action has been assumed to be through
      asexualization with its secondary effects on sexual behavior. This study shows
      that the mechanism may be more complex and may involve a differential effect on
      sexual arousal patterns. Treatment responses may differ in high and low plasma
      testosterone groups.

PMID- 8285850
TI  - Species-specific pharmacokinetics of styrene in rat and mouse.
AB  - The pharmacokinetics of styrene were investigated in male Sprague-Dawley rats and
      male B6C3F1 mice using the closed chamber technique. Animals were exposed to
      styrene vapors of initial concentrations ranging from 550 to 5000 ppm, or
      received intraperitoneal (i.p.) doses of styrene from 20 to 340 mg/kg or oral
      (p.o.) doses of styrene in olive oil from 100 to 350 mg/kg. Concentration-time
      courses of styrene in the chamber atmosphere were monitored and analyzed by a
      pharmacokinetic two-compartment model. In both species, the rate of metabolism of
      inhaled styrene was concentration dependent. At steady state it increased
      linearly with exposure concentration up to about 300 ppm; more than 95% of
      inhaled styrene was metabolized and only small amounts were exhaled unchanged. At
      these low concentrations transport to the metabolizing enzymes and not their
      metabolic capacity was the rate limiting step for metabolism. Pharmacokinetic
      behaviour of styrene was strongly influenced by physiological parameters such as
      blood flow and especially the alveolar ventilation rate. At exposure
      concentrations of styrene above 300 ppm the rate of metabolism at steady state
      was progressively limited by biochemical parameters of the metabolizing enzymes.
      Saturation of metabolism (Vmax) was reached at atmospheric concentrations of
      about 700 ppm in rats and 800 ppm in mice, Vmax being 224 mumol/(h.kg) and 625
      mumol/(h.kg), respectively. The atmospheric concentrations at Vmax/2 were 190 ppm
      in rats and 270 ppm in mice. Styrene accumulates preferentially in the fatty
      tissue as can be deduced from its partition coefficients in olive oil:air and
      water:air which have been determined in vitro at 37 degrees C to be 5600 and 15.
      In rats and mice exposed to styrene vapors below 300 ppm, there was little
      accumulation since the uptake was rate limiting. The bioaccumulation factor
      body:air at steady state (K'st*) was rather low in comparison to the
      thermodynamic partition coefficient body:air (Keq) which was determined to be
      420. K'st* increased from 2.7 at 10 ppm to 13 at 310 ppm in the rat and from 5.9
      at 20 ppm to 13 at 310 ppm in the mouse. Above 300 ppm, K'st* increased
      considerably with increasing concentration since metabolism became saturated in
      both species. At levels above 2000 ppm K'st* reached its maximum of 420 being
      equivalent to Keq. Pretreatment with diethyldithiocarbamate, administered
      intraperitoneally (200 mg/kg in rats, 400 mg/kg in mice) 15 min prior to exposure
      of styrene vapours, resulted in effective inhibition of styrene metabolism,
      indicating that most of the styrene is metabolized by cytochrome P450-dependent
      monooxygenases.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8285851
TI  - Comparative metabolism of bis(2-methoxyethyl)ether in isolated rat hepatocytes
      and in the intact rat: effects of ethanol on in vitro metabolism.
AB  - The metabolism of the reproductive and developmental toxicant bis(2
      methoxyethyl)ether (diglyme) was studied in isolated rat hepatocytes and in the
      intact rat. Male Sprague-Dawley rats (190-220 g) were used in both studies.
      Hepatocytes, isolated by a two-step in situ collagenase perfusion of the liver,
      were cultured as monolayers and incubated with [14C]diglyme at 1, 10, 30, and 50
      microM for up to 48 h. For the in vivo study, rats were given single oral doses
      of [14C]diglyme at 5.1 mmol/kg body wt, and urine was collected for up to 96 h.
      Radioactive compounds in the culture medium or in the urine were separated by
      high performance liquid chromatography and quantified with an in-line
      radioactivity monitor. Metabolites were identified by comparison of their
      chromatographic retention times and their mass spectra with those of authentic
      compounds. The principal metabolite from hepatocytes and in the urine was (2
      methoxyethoxy)acetic acid (MEAA). This metabolite accounted for approximately 36%
      of the radioactivity in the 48-h culture medium and about 67% of the administered
      dose in the 48-h urine. Other prominent metabolites common to both systems
      included 2-(2-methoxyethoxy)ethanol, methoxyacetic acid (MAA), 2-methoxyethanol,
      and diglycolic acid. The diglyme metabolite profiles from urine and from
      hepatocytes were qualitatively similar, demonstrating that, in the rat,
      hepatocytes serve as a good model system for predicting the urinary metabolites
      of diglyme. Moreover, MEAA was shown to be the metabolite best suited for use as
      a short-term biological marker of exposure to diglyme.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8285852
TI  - Effect of various non-hepatotoxic compounds on urinary and liver taurine levels
      in rats.
AB  - Administration of compounds which alter protein synthesis or sulphur amino acid
      metabolism in rats results in changes in the excretion of urinary taurine.
      Treatment with diethylmaleate (DEM) or phorone, which will deplete glutathione
      (GSH), reduces taurine excretion, whereas treatment with buthionine sulphoximine
      (BSO), which will inhibit glutathione synthesis, increases taurine excretion.
      Treatment with cycloheximide, an inhibitor of protein synthesis, increases
      taurine excretion, whereas pretreatment with phenobarbital, which will increase
      protein synthesis, decreases taurine excretion. Administration of agents which
      damage organs other than the liver such as the kidney, heart and testes, does not
      increase urinary taurine.

PMID- 8285854
TI  - DNA cleavage by metabolites of butylated hydroxytoluene.
AB  - The effect of butylated hydroxytoluene (BHT) and its metabolites on DNA cleavage
      in vitro was studied with supercoiled plasmid DNA, pUC18, by agarose gel
      electrophoresis. Among several BHT metabolites, 2,6-di-t-butyl-p-benzoquinone
      (BHT-quinone) caused cleavage of supercoiled DNA (form I) at a concentration as
      low as 1 x 10(-6) M. The relative amount of linear form (form III) was increased
      with increasing concentration of BHT-quinone. 2,6-Di-t-butyl-4-hydroperoxy-4
      methyl-2,5-cyclohexadienone (BHT-peroxyquinol) and 3,5-di-t-butyl-4
      hydroxybenzaldehyde (BHT-CHO) also cleaved DNA, but to a lesser extent than BHT
      quinone. No DNA cleavage was detected by BHT, 2,6-di-t-butyl-4-hydroxymethyl
      phenol (BHT-OH), 3,5-di-t-butyl-4-hydroxybenzoic acid (BHT-COOH), 2,6-di-t-butyl
      4-hydroxy-4-methyl-2,5-cyclohexadienone (BHT-quinol) or 2,6-di-t-butyl-4
      methylene-2,5-cyclohexadienone (BHT-quinone methide). The DNA cleavage by BHT
      quinone was inhibited by oxygen radical scavengers including superoxide dismutase
      (SOD), catalase, polyethylene glycol, t-butyl alcohol, dimethyl sulfoxide, sodium
      azide, sodium benzoate, bovine serum albumin and methionine, while it was
      enhanced by the addition of FeCl2. The production of superoxide radical in a
      solution of BHT-quinone was confirmed by cytochrome c reduction assay. Superoxide
      was not produced by BHT or other BHT metabolites except for BHT-quinone. These
      results suggest that BHT-quinone, one of the principal metabolites of BHT,
      cleaves DNA strands via its generation of oxygen radicals.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8285853
TI  - Antioxidative stress therapy with dithiothreitol tetraacetate. I. Protection
      against carbon tetrachloride induced liver necrosis.
AB  - Dithiothreitol (DTT) is known to prevent or even reverse several deleterious
      effects of radiation or of chemical agents operating via free radical and
      oxidative stress. However, its use has been hampered by its chemical instability
      and toxic properties. In this work, we synthesized and characterized
      dithiothreitol tetraacetate (DTT-Ac) which is less toxic and chemically stable,
      and we provided GLC/MS evidence that it is able to rapidly generate fully
      deacetylated DTT in liver after its administration to rats. Treatment with DTT-Ac
      simultaneously with CCl4 or 3 h after the hepatotoxin was able to significantly
      prevent the CCl4-induced liver necrosis at 24 h after poisoning. DTT-Ac
      administration was able to significantly reduce the intensity of the covalent
      binding of CCl4 reactive metabolites to microsomal lipids (CB), but it did not
      prevent the CCl4-induced initiation of a lipid peroxidation (LP) process as
      evidenced by diene hyperconjugation of microsomal lipids. Results suggest that
      DTT-Ac protective effects might be due to its in vivo conversion to DTT which in
      turn would decrease the intensity of CB via different potential mechanisms to be
      explored. Protection cannot be attributed to decreases in levels of CCl4 reaching
      the liver or to chain breaking effects on LP.

PMID- 8285855
TI  - Ultrastructure of the cortical epithelium of the rat thymus after in vivo
      exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known for inducing cortical atrophy
      in the rat thymus. The present study was conducted to provide ultrastructural
      evidence for the cortical epithelium to be a target for TCDD in vivo. Juvenile
      male Wistar rats were orally intubated once with either 50 or 150 micrograms/kg
      TCDD and killed 4 or 10 days thereafter. Major changes were found in the cortical
      thymic epithelium. First, a relative shift occurred from "pale" to darker
      cortical epithelial cell types, as judged by their nuclear and cytoplasmic
      electron density. This effect was most prominent at 10 days after exposure to 150
      micrograms/kg TCDD. The increased electron density of the cortical epithelium
      indicates an altered state of cellular differentiation. Secondly, at the 150
      micrograms/kg dose level focal epithelial cell aggregates were seen both at day 4
      and day 10 after administration. This aggregation may either be compound induced
      or represent a secondary event to the collapse of the thymic stroma. Thirdly,
      increased vacuolation of cortical epithelial cells was apparent. This effect is
      interpreted as a consequence rather than a cause of thymocyte depletion from the
      cortex. This study indicates that TCDD exposure affects the cortical epithelium
      of the rat thymus at a high dose level. Electron microscopy reveals that the
      differentiation of epithelial cells is altered. In addition, epithelial cell
      aggregates are formed.

PMID- 8285856
TI  - Effect of tumor promoting stimuli on gap junction permeability and connexin43
      expression in ARL18 rat liver cell line.
AB  - The ARL18 rat liver cell line has previously been used for screening tumor
      promoters in the metabolic cooperation assay (Williams 1980; Williams et al.
      1981; Telang et al. 1982). These cells display high levels of gap junctional
      communication, as assessed functionally and immunologically. Intracellularly
      injected Lucifer Yellow diffused extensively and there was rapid fluorescent
      recovery after photobleaching. Moreover, expression of connexin43 (Cx43) was high
      as evaluated by immunocytochemistry of cell monolayers and Western blot analysis
      of total cell homogenates. Western blot analysis revealed multiple forms of Cx43,
      which presumably correspond to known dephosphorylated and phosphorylated states
      of this protein. Gap junction permeability and Cx43 expression in ARL18 cells
      were studied after exposure to the tumor promoters 12-0-tetradecanoyl-phorbol-13
      acetate (TPA), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (DDT), and
      after wounding the cell monolayer. TPA and DDT strongly inhibited gap junction
      permeability; whereas monolayer wounding did not affect the degree of fluorescent
      recovery after injury, either in the cells on the edge of the wound or in distal
      regions. No changes in the cellular distribution of Cx43 were observed after any
      of these treatments, although Western blots revealed a decrease in total Cx43
      after 24-h exposure to DDT (10 micrograms/ml) and a slight increase after TPA
      treatment (30 min, 0.1 microgram/ml). Relative abundance of different
      phosphorylated Cx43 forms was increased after 1 h exposure to DDT (10 micrograms)
      and 30 min exposure to TPA (0.1 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285857
TI  - Fluoride toxicity: a biochemical and scanning electron microscopic study of
      enamel surface of rabbit teeth.
AB  - The present study has been carried out to investigate the effect of fluoride
      toxicity on the morphology as well as inorganic chemical constituents of rabbit
      teeth. Rabbits were administered sodium fluoride at a dose of 10 mg NaF/kg body
      weight every 24 h for 18 and 23 months. The incisor and molar teeth (whole tooth)
      were investigated for fluoride, calcium and phosphorus content in 18- and 23
      month treated animals. The enamel surfaces of incisor teeth of 23-month treated
      animals were examined under scanning electron microscope. A significant increase
      in fluoride levels and significant decrease in calcium content was found
      following fluoride administration for 18 and 23 months as compared to control.
      Ca/P ratio was significantly increased only in 23-month treated animals. The
      scanning electron micrographs revealed hypoplastic, rough, uneven, pitted and
      cracked enamel surfaces covered with granular deposits as a result of excessive
      intake of fluoride. It can be concluded that long term fluoride administration
      leads to severe structural alterations on the enamel surface, possibly through
      defective mineralization.

PMID- 8285858
TI  - Genotoxic effects of subacute treatments with wood dust extracts on the nasal
      epithelium of rats: assessment by the micronucleus and 32P-postlabelling.
AB  - Human exposure to wood dust has been epidemiologically linked to a number of
      enhanced incidences of various neoplasias, including those of the nose. Among
      different suspected woods, long-term exposure to the dust of beech (Fagus
      silvatica) is strongly associated with development of these tumors.
      Experimentally, it has been shown that a simple alcoholic extract of beech wood
      dust is mutagenic toward some bacteria and tumorigenic on mouse skin. For the
      present study, different groups of male Wistar rats were treated with aqueous,
      ethanol, or methanol extract of untreated beech wood dust via nasal drip at three
      concentrations for 48 h. Animals were killed 24 h after the last treatment and
      the nasal tissues were isolated to be examined for possible induction of
      micronuclei and DNA adducts. A clear dose-dependent increase in the number of
      micronuclei (P < 0.01) was observed after treatment of rats with each alcoholic
      extract of wood dust. In contrast, no DNA adducts could be detected with these
      extracts using the 32P-postlabelling technique. No increased number of
      micronucleated cells was found with solvents alone or with aqueous extract of
      dust. These data might support the early hypothesis that wood dust per se
      contains some in vivo genotoxic and thus possibly carcinogenic components
      extractable by an alcohol.

PMID- 8285859
TI  - [Pediatric heart surgery in a general hospital. Procedures and results in a 5
      years' experience].
AB  - PURPOSE: To establish the routines for pediatric cardiac surgery in a general
      hospital, with a view to accurate diagnostic, a more precise intervention, a
      reduction of the risks and consequently an improvement of the results. METHODS:
      Three hundred and ninety surgeries were carried out in children with congenital
      heart disease. The method use highlighted noninvasive diagnosis, joint lodging,
      reduced period of hospitalization, care with the collection and preservation of
      blood, as well as the preference for fresh blood, techniques of monitoring,
      anesthesia, cardiopulmonary bypass and myocardial protection, concern with
      aesthetic incision for female patients and postoperative critical care. RESULTS:
      A high rate of early extubation was observed, with a significant reduction of the
      pulmonary complications resulting from prolonged mechanical ventilation. Low
      haemodynamic instability, arrhythmia and postoperative bleeding rates were
      uncommon. The low mortality rate and the average hospitalization period confirmed
      the good results. CONCLUSION: With the establishment of routines for pediatric
      cardiac surgery, we observed a progressive improvement of the results, with low
      rates of morbidity and mortality in a general hospital.

PMID- 8285860
TI  - [Acute effects of propafenone in patients with ventricular pre-excitation].
AB  - PURPOSE: To evaluate the electrophysiological effects of intravenous propafenone
      in the anterograde and retrograde effective refractory period of the accessory
      pathways (AP), in patients with Wolff-Parkinson-White syndrome. METHODS: Forty
      symptomatic patients were studied. All patients were undergone to
      electrophysiologic study at baseline and after IV propafenone (2.0mg/kg). Drug
      effects were analysed according to the basal state of the anterograde and
      retrograde effective refractory periods of the AP > < 270ms. RESULTS: The mean
      anterograde and retrograde effective refractory periods of the AP were 275 +/-
      76ms and 264 +/- 44ms at the control and 462 +/- 190ms and 438 +/- 184ms after
      drug respectively (p < 0.01 in both situations). The mean anterograde effective
      refractory period of the AV node was 236 +/- 40ms (control) and 276 +/- 57ms
      (post-drug)- p < 0.05. The mean atrial and right ventricular effective refractory
      period in the control were 210 +/- 23ms and 240 +/- 34ms passing to 215 +/- 24ms
      and 250 +/- 40 ms after drug respectively (p = ns). After drug, complete
      anterograde and retrograde block of the AP, occurred in 15 (42%) and 12 (35%)
      patients respectively. Out of 15 patients with complete anterograde block of the
      AP, 11 had anterograde effective refractory period of the AP > 270ms and 4, <
      270ms (p < 0.02). Out of 12 patients with complete retrograde block of the AP
      after drug, 4 had retrograde effective refractory period > 270ms and 8, < 270ms
      (p: ns). CONCLUSION: Propafenone caused significant increase in the anterograde
      and retrograde effective refractory periods of the AP. There was a tendency of
      the drug to show better effectiveness in patients with anterograde effective
      refractory period of the AP > 270ms. This results were not seen in relation to
      the retrograde effective refractory period of the AP.

PMID- 8285861
TI  - [Lovastatin in the treatment of hypercholesterolemia in non-insulin-dependent
      diabetes mellitus patients].
AB  - PURPOSE: To evaluate the effects of lovastatin as an hypocholesterolemic agent in
      non-insulin dependent diabetic (NIDDM) patients with high cholesterol plasma
      levels. METHODS: Twenty NIDDM patients were included in this study.
      Hypercholesterolemia was defined as LDL-cholesterol plasma levels above 160mg/dl
      in female patients and above 130mg/dl in male patients or in women presenting any
      other risk factor for cardiovascular disease. From the 20 patients included, 18
      had also high levels of arterial blood pressure. They were evaluated for
      admission in the study after they have substituted the antihypertensive
      medication for at least 6 weeks, from beta-blockers or diuretics to angiotensin
      converting enzyme inhibitors or calcium channel blockers. Lovastatin was
      administered in a initial daily dose of 20mg to all patients for 6 weeks. After
      this period this dose was increased to 40mg in 11 patients with LDL-cholesterol
      levels above 130mg/dl. All patients were treated for a total period of 24 weeks.
      RESULTS: Lovastatin therapy for 24 weeks reduced LDL-cholesterol and total
      cholesterol plasma levels in 30% and 21%, respectively, while no changes in HDL
      cholesterol or triglycerides plasma levels were observed. The medication was well
      tolerated and no changes in bilirrubins or transaminases plasma levels were
      detected. In 9 patients the serum levels of alkaline phosphatase showed an
      elevation and the mean level of all group increased from 109 +/- 59 to 188 +/-
      60m mu/ml (p < 0.05). This was an isolated abnormality without any other clinical
      manifestation. CONCLUSION: Lovastatin in NIDDM showed to be an efficient agent to
      reduce high levels of LDL-cholesterol and total cholesterol. However, the
      importance of the abnormality observed in serum alkaline phosphatase levels
      deserves further investigation. In this condition we recommend discontinuation of
      lovastatin therapy.

PMID- 8285862
TI  - [The scientific impact of the nitric oxide discovery as vasodilator and
      endogenous antithrombotic agent].

PMID- 8285863
TI  - [Atrial septostomy at the intensive care unit under echocardiographic monitoring.
      Initial experience of the Heart Institute of Pernambuco].
AB  - The present article describes the initial experience of the Instituto do Coracao
      de Pernambuco, at the neonatal intensive care unit, with the performance of
      Rashkind atrioseptostomy under two-dimensional echocardiographic control, through
      percutaneous venous approach (right femoral vein catheterization), under local
      anaesthesia, in three cases, two neonates with transposition of the great
      arteries and one with tricuspid atresia. In two children the procedure was
      successful both technically and haemodynamically. In the third child, aged 36
      days, the atrial septum was thickened not allowing for satisfactory withdraw. In
      none of the three cases significant complications were observed during the
      procedure. Despite of the small number of patients, our experience showed that
      this new approach to the performance of Rashkind atrioseptostomy is feasible
      without major complications to the neonate and with advantages over the
      conventional technique.

PMID- 8285864
TI  - [Coronary angioplasty using double balloon in artery of large calibre (hugging
      balloons)].
AB  - In this case report the transluminal coronary angioplasty was performed in a
      oversized right coronary artery with a severe lesion with thrombus inside, using
      the Hugging balloon technique (two dilatation balloon catheters used
      simultaneously). This technique achieved minimal residual lesion and had a
      favorable clinical outcome of the patient.

PMID- 8285865
TI  - [Coronary-cavitary fistula. Embryogenesis and report of a case surgically
      treated].
AB  - The authors report the case of a 6-year-old female patient with congenital left
      coronary artery-right cardiac chamber fistula. The anomalous communication began
      at the left main coronary artery and extended to the top of the heart, throughout
      the myocardial muscle thickness. Diagnosis done by 2-D echocardiogram and
      cineangiography. The patient underwent to surgical treatment and both sides of
      the anomalous fistula was closed with pericardium bovinus patch. There was found
      no arterial ventricular branch originary of the fistulas course. The patient had
      a good post-operative outcome and there was no clinical or laboratorial evidences
      of myocardial ischemia.

PMID- 8285866
TI  - [Aortic arch interruption with restrictive ductus arteriosus].
AB  - Interruption of the aortic arch is an uncommon cardiovascular anomaly. It is
      usually associated with a large ductus arteriosus (DA) and interventricular
      septal defects. Two cases of one and two month old girls with restrictive DA are
      reported. The clinical, anatomical and surgical findings are discussed.

PMID- 8285867
TI  - [Refractory heart failure and sepsis in a patient with hypertrophic
      cardiomyopathy].
AB  - A twenty one years old man with obstructive hypertrophic cardiomyopathy with
      resting gradient and which develops subacute infectious endocarditis and acute
      mitral regurgitation by valvular apparatus destruction. During the course occurs
      refractory heart failure and sepsis. The association between these diseases and
      difficulties in management are analyzed, and literature is reviewed. It is
      emphasized the high mortality of this condition and indication for surgical
      referral, as well the necessity for infectious endocarditis prophylaxis in
      patients with obstruction at rest.

PMID- 8285868
TI  - [Embolomycotic pseudoaneurysm of the common femoral artery in infective
      endocarditis].
AB  - A male patient, six years old, with mitral valve endocarditis presented with
      pseudoaneurysm of the right femoral artery. He was submitted to surgical
      treatment with reconstruction of the artery with good outcome.

PMID- 8285869
TI  - [Restenosis after angioplasty. "Excessive cicatrization"? Diagnosis, management
      and perspectives].

PMID- 8285870
TI  - [Treatment of systemic arterial hypertension with urapidil. Study in mild and
      moderate hypertension with ambulatory monitoring of arterial pressure].
AB  - PURPOSE: To study the efficacy and tolerability of urapidil in patients with mild
      and moderate arterial hypertension, including ambulatory blood pressure
      monitoring (ABPM). METHODS: Twenty patients, either sex, 40 to 75 years old, with
      diastolic blood pressure (DBP) between 90 to 115mmHg were studied. The DBP was
      the follow-up criterion measured by conventional esphygmomanometer. The 24 hours
      ambulatory monitoring of BP was made to observe its variation. After wash-out of
      15 days, urapidil was administered starting with 60 mg/day, during two weeks,
      followed by 120mg/day and 180mg/day if necessary, to achieve th protocol baseline
      of 90mmHg or less of DBP. It followed 8 weeks treatment. Laboratory tests, EKG,
      monitoring of BP and clinical evaluation was made at pre and post treatment
      period, with clinical examinations every two weeks. RESULTS: In 15 (75%) patients
      the BP was controlled according to the protocol criteria (p < 0.001). The control
      of BP was not achieved in 3 (15%) and 2 (10%) patients were withdrawn because of
      intolerable drug side effects. The most frequent side effects were nausea,
      dizziness and indisposition, but 60% of the patients did not present any one. The
      duration of side effects was not longer than to 30 days, except in one patient.
      There were no changes in laboratory results after the treatment period. The 24
      hours ABPM showed an improvement in the pattern of hypertension, maintaining the
      BP circadian rhythm. CONCLUSION: Urapidil demonstrated to be effective and safe
      in the treatment of patients with mild and moderate arterial hypertension,
      showing good control of BP levels, without changing the laboratory parameters.

PMID- 8285871
TI  - [Are the spontaneous coronary recanalization and the coronary collateral
      circulation really important in the left ventricular preservation in acute
      myocardial infarct?].
AB  - PURPOSE: To determine if maintenance of residual blood flow to culprit coronary
      artery in acute myocardial infarction is important in preserving left ventricular
      systolic function. METHODS: Prospective study of 63 consecutive survivors of
      acute myocardial infarction in the prethrombolytic era that were submitted to
      cinecoronary angiography and 30 degrees RAO left ventriculography on the 4th
      week. Culprit coronary artery patency and collateral circulation were correlated
      with global and segmental left ventricular contractility. RESULTS: Spontaneous
      coronary recanalization correlated significantly with better left ventricular
      systolic function only in patients with anterior wall myocardial infarction. This
      relationship was stronger with segmental than with global contractility. Besides,
      it was seen that absence of recanalization of pre-septal left anterior descending
      coronary artery occlusion resulted in significantly worse global and segmental
      left ventricular systolic function than post-septal occlusion, resulting in left
      ventricular aneurysm in all patients (2/3 of recanalized patients versus 1/3 of
      post-septal occlusions). Collateral circulation to culprit coronary artery
      correlated significantly with better global and segmental left ventricular
      contractility only in patients with inferior wall myocardial infarction.
      CONCLUSION: In acute anterior wall myocardial infarction spontaneous coronary
      artery recanalization is associated with better global and segmental left
      ventricular systolic function, specially if the occlusion is of pre-septal
      localization, while collateral circulation is not related to better
      contractility. In acute inferior wall myocardial infarction one sees the reverse.

PMID- 8285872
TI  - The Dutch model of maternity care.

PMID- 8285873
TI  - Trial of labour.

PMID- 8285874
TI  - Trial of labour--thoughts and feelings of the midwife participant.

PMID- 8285875
TI  - Born before arrival--mother nature accoucheur.

PMID- 8285876
TI  - Variation in healing throughout the depth of long-term, unsutured, corneal wounds
      in human autopsy specimens and monkeys.
AB  - OBJECTIVE: To determine regional differences in stromal wound healing morphologic
      features in long-term radial keratotomy wounds. METHODS: Unsutured, semiradial,
      nonperforating wounds in seven monkeys and 10 human autopsy specimens obtained
      3.5 to 52 months after surgery were analyzed using light, transmission, and
      fluorescent microscopy. RESULTS: Monkeys showed fast healing, whereas all human
      specimens had one or more incisions containing a superficial epithelial plug.
      Completely healed wounds in both models had fibroblast orientation and
      ultrastructural "pseudolamellar" (ie, colinear collagen fiber) continuity across
      the anterior wound, compared with disorganization of the midposterior scar.
      CONCLUSIONS: Regional differences in healing rates, mechanical factors associated
      with epithelial plug elimination, intrinsic tissue characteristics, and/or
      induction of pseudolamellar repair by the epithelial plug may explain variation
      in healing within an unsutured corneal wound.

PMID- 8285877
TI  - Bipolar surface electrical stimulation of the vertebrate retina.
AB  - BACKGROUND: Retinitis pigmentosa with attendant photoreceptor loss can cause a
      profound visual handicap. We have postulated that an intraocular prosthesis that
      could electrically stimulate the inner retina might provide vision to some of
      these patients. For such a prosthesis to be feasible, electrical stimulation of
      the inner retina must elicit a focal retinal response. The stimulating current
      densities required to elicit such a response must not result in irreversible
      toxic reactions at the electrode-tissue interface. METHODS: To test the
      feasibility of this approach, we used bipolar platinum wire electrodes to
      electrically stimulate the inner retinal surface in bullfrog eyecup preparations
      and, using similar methods, we electrically stimulated rabbit eyes after
      injecting intravenous sodium iodate (40 mg/kg), a retinal pigment epithelial
      toxin with secondary effects on the photoreceptors. RESULTS: Surface electrical
      stimulation of the inner retina in normal eyes and in eyes with outer retinal
      degeneration can elicit a localized retinal response. The threshold stimulating
      currents resulted in charge densities of 2.98 microcoulombs per square centimeter
      (bullfrog), 8.92 microC/cm2 (normal rabbit), and 11.9 microC/cm2 (rabbit retinas
      with outer retinal degenerations). These charge densities are within the
      previously delineated safe limits for long-term electrical stimulation of neural
      tissue using platinum microelectrodes (100 microC/cm2). CONCLUSION: Multifocal
      electrical stimulation of the retina might be a viable approach to provide some
      vision to patients who have profound visual loss due to outer retinal
      degenerations.

PMID- 8285878
TI  - Localization and quantitation of blood-retinal barrier breakdown in experimental
      proliferative vitreoretinopathy.
AB  - OBJECTIVE: To determine the contribution of the breakdown of the blood-retinal
      barrier (BRB) as measured with magnetic resonance imaging in the development of
      retinal detachment in an experimental model of proliferative vitreoretinopathy.
      METHODS: Contrast-enhanced magnetic resonance imaging was used to evaluate BRB
      breakdown in an intravitreal cell-injection model of proliferative
      vitreoretinopathy. Intravitreal injection of 2.5 x 10(5) homologous dermal
      fibroblasts produced specific disruption of the inner, or vascular, BRB. RESULTS:
      Breakdown of the BRB was greatest in the first 3 days after injection, confirming
      previous work using fluorescein-based methods. Injection of 1 mg of intravitreal
      triamcinolone acetonide at the time of cell injection significantly reduced both
      BRB breakdown and the incidence of eventual traction retinal detachment. Eyes
      that did develop detachment had significantly greater leakage prior to its
      development than those that did not, regardless of steroid treatment.
      CONCLUSIONS: Quantitation and definitive localization of BRB leakage with
      magnetic resonance imaging provides a better understanding of the relationship
      between BRB compromise and the development of retinal detachment in this
      frequently used model.

PMID- 8285879
TI  - Giant cavernous hemangioma of the face.

PMID- 8285880
TI  - Artificial orbit for experimental surgery on the anterior segment.

PMID- 8285881
TI  - Ceftazidime or amikacin: choice of intravitreal antimicrobials in the treatment
      of postoperative endophthalmitis.

PMID- 8285882
TI  - Intraocular ceftazidime as an alternative to the aminoglycosides in the treatment
      of endophthalmitis.

PMID- 8285883
TI  - Ganciclovir intraocular device and patient survival.

PMID- 8285884
TI  - Ganciclovir intraocular device and patient survival.

PMID- 8285885
TI  - Phototherapeutic keratectomy in recurrent corneal intraepithelial dysplasia.

PMID- 8285886
TI  - Postpartum Brown's syndrome.

PMID- 8285887
TI  - Optic nerve sheath decompression with adjunctive mitomycin and Molteno device
      implantation.

PMID- 8285888
TI  - Measuring the benefit and value of services.

PMID- 8285889
TI  - High-dose corticosteroid regimen retards development of multiple sclerosis in
      optic neuritis treatment trial.

PMID- 8285890
TI  - The nerve of glaucoma!
AB  - Contemporary concepts of open angle glaucoma suggest that the current emphasis on
      reduction of elevated intraocular pressure could be augmented by other
      therapeutic approaches. In this article, we describe significant recent
      developments in the molecular and cellular biology and neuropharmacology of nerve
      damage that are likely, in coming years, to suggest new therapeutic approaches to
      the management of glaucoma. These developments may lead to the achievement of
      pharmacologic protection of the optic nerve from damage or possibly promotion of
      reversal of damage. We review selected studies of excitotoxins and N-methyl-D
      aspartate receptor antagonists, Ca(2+)-induced damage and calcium channel
      blockers, the intracellular messenger nitric oxide and its perturbation, free
      radical damage and scavengers, nerve regeneration, and growth factors. Several
      basic research questions are posed, answers to which may transform our concepts
      of glaucoma therapy.

PMID- 8285891
TI  - Empiric treatment of endophthalmitis. Are aminoglycosides necessary?
AB  - OBJECTIVE: To reevaluate the necessity of empiric gram-negative therapy for
      postoperative endophthalmitis based on the recognition of aminoglycoside-induced
      toxic effects. METHODS: A review of 162 cases of culture-positive bacterial
      endophthalmitis to determine bacterial prevalence, antibiotic susceptibilities,
      and laboratory staining results of intraocular material. RESULTS: One hundred
      fifty (93%) gram-positive and 12 (7%) gram-negative isolates. All the gram
      positive bacteria were susceptible to vancomycin hydrochloride; and gram-negative
      bacteria were susceptible to gentamicin sulfate, amikacin sulfate, and
      ceftazidime sodium. Bacterial rods were observed on smear of intraocular material
      in 10 gram-negative cases submitted for examination. CONCLUSION: Vancomycin is an
      appropriate single agent if laboratory studies rule out gram-negative infection.
      In the absence of laboratory support, an aminoglycoside (possible toxic effects)
      or another gram-negative antibiotic (possibly ceftazidime) should also be
      administered.

PMID- 8285892
TI  - Aminoglycoside toxicity in the treatment of endophthalmitis. The Aminoglycoside
      Toxicity Study Group.
AB  - OBJECTIVE AND METHODS: Intravitreous aminoglycosides are widely used for the
      treatment and prophylaxis of endophthalmitis. Because the toxicity of 0.4 mg of
      gentamicin sulfate is well documented, many surgeons now use amikacin sulfate or
      low-dose gentamicin to reduce the risk of macular infarction. A survey of retinal
      specialists has suggested that amikacin or low-dose gentamicin can also cause
      macular toxic side effects. To further investigate this issue, the critical
      details of the case histories, findings, and course of 13 patients who received
      intravitreous injections of 0.2 to 0.4 mg of amikacin sulfate or 0.1 to 0.2 mg of
      gentamicin sulfate for prophylaxis or treatment of endophthalmitis are
      summarized. For several patients, complete case histories and a fluorescein
      angiogram are provided. RESULTS: These cases suggest that amikacin and low-dose
      gentamicin, similar to gentamicin sulfate at a dose of 0.4 mg, can cause macular
      infarction. The causative dose cannot be ascertained in any of the cases, but
      doses were prepared by hospital pharmacists using typewritten protocols, a
      practice that helps to prevent dilution errors. Several of these cases differ
      from previously reported cases of aminoglycoside toxicity in that the involvement
      of the macula was quite discrete. Most of the patients suffered severe visual
      loss, but two patients, in whom most of the nonperfusion was adjacent to the
      macula and in whom some of the perifoveal capillaries were spared, recovered
      20/50 visual acuity. CONCLUSIONS: These cases emphasize the potential hazards of
      the intravitreous use of aminoglycosides. A toxic reaction can occur even when
      injection of low doses is intended and precautions are made to avoid dilution
      errors. A localized increase in concentration in dependent areas of the retina
      may play a role in aminoglycoside toxicity. If some of the perifoveal capillaries
      are spared, retention of some central vision is possible. Consideration should be
      given to substituting ceftazidime for aminoglycosides for the treatment and
      prophylaxis of endophthalmitis.

PMID- 8285893
TI  - Presumed occlusion of posterior ciliary arteries following central retinal vein
      decompression surgery.
AB  - OBJECTIVE: Sectioning of the posterior scleral ring has been advocated in the
      treatment of central retinal vein occlusion. We reviewed cases in which this
      surgery apparently produced sectioning or closure of the short and long posterior
      ciliary arteries that resulted in a triangular area of choroidal ischemia and
      permanent chorioretinal lesions. DESIGN: Case series. SETTING: Clinic-based
      vitreoretinal referral practice. PATIENTS: Four eyes of three patients whose ages
      ranged from 17 to 53 years underwent sectioning of the posterior scleral rings as
      treatment for central retinal vein occlusion. MAIN OUTCOME MEASURES: Findings
      from complete ophthalmologic evaluation. RESULTS: All patients had either an oval
      or a triangular area of choroidal ischemia nasal to the optic disc and had
      permanent chorioretinal lesions. CONCLUSIONS: Valid basis for performing this
      operation requires further investigation.

PMID- 8285894
TI  - Treatment of bleb infection after glaucoma surgery.
AB  - OBJECTIVE: To assess the history, clinical course, and response to treatment of
      14 patients with a bleb infection (blebitis) following glaucoma surgery. DESIGN:
      Retrospective study. SETTING: A university referral center in Atlanta, Ga.
      PATIENTS: Fourteen patients developed a bleb infection that ranged from 1 month
      to 22 years after glaucoma surgery. Infections were characterized by pain, a
      whitened bleb surrounded by intense conjunctival injection, marked anterior
      chamber reaction (hypopyon in six eyes), and a clear vitreous. Before infection,
      most blebs were described as thin. The results of Seidel's test were positive in
      six patients, and most patients had a low intraocular pressure without the use of
      any glaucoma medication. INTERVENTION: Treatment consisted of hospitalization,
      intravenous antibiotic therapy, and hourly topical fortified cefazolin sodium and
      gentamicin sulfate. RESULTS: The visual acuity in most patients improved to the
      level before the bleb infection, with only three eyes losing 2 or more lines of
      vision. CONCLUSIONS: Bleb infection without vitreous involvement (blebitis) may
      be a precursor of endophthalmitis. With aggressive treatment, bleb infection
      appears to have a much better prognosis for visual recovery than endophthalmitis.

PMID- 8285895
TI  - Trabeculectomy with releasable sutures.
AB  - OBJECTIVE: To determine whether the use of releasable scleral-flap sutures
      affects the success rate and the incidence of complications following
      trabeculectomy. DESIGN: A retrospective chart review of a consecutive series of
      trabeculectomies. SETTING: A university-based referral practice. PATIENTS: Two
      hundred fifty-eight consecutive patients (274 eyes) undergoing trabeculectomy
      because of uncontrolled glaucoma. INTERVENTION: During the first year, 124
      patients (128 eyes) underwent trabeculectomies with permanent scleral-flap
      sutures. During the second year, 134 patients (146 eyes) underwent
      trabeculectomies with releasable scleral-flap sutures. MAIN OUTCOME MEASURES:
      Incidence of flat and shallow anterior chamber, incidence of operations to drain
      choroidal detachment and to re-form anterior chamber, and long-term control of
      intraocular pressure. RESULTS: In the group with permanent sutures, 42 eyes
      (32.8%) had clinically detectable shallowing of the anterior chamber in the early
      postoperative period. In contrast, a shallow anterior chamber was noted in 21
      eyes (14.4%) in the group with releasable sutures (P = .0003). Flat anterior
      chamber, defined as iridocorneal apposition to the pupil margin, occurred in 11
      eyes with permanent sutures (8.6%) but in only two eyes (1.4%) with releasable
      sutures (P = .0078). Surgical intervention to drain suprachoroidal fluid and re
      form the anterior chamber was required in eight eyes with permanent sutures
      (6.2%) but in only one eye with releasable sutures (0.7%) (P = .014). At 1-year
      follow-up, the two groups were similar in terms of intraocular pressure and the
      need for ocular hypotensive medications. CONCLUSIONS: Releasable scleral-flap
      sutures reduce the incidence of shallow and flat anterior chamber after
      trabeculectomy without compromising long-term control of intraocular pressure.

PMID- 8285896
TI  - Oral imipramine and acute angle closure glaucoma.
AB  - OBJECTIVE: To document acute angle closure glaucoma temporally related to
      ingestion of oral imipramine hydrochloride. PATIENTS: Four patients with narrow
      angles received routinely prescribed doses of imipramine that triggered acute
      angle closure glaucoma. OUTCOME: Laser iridotomy was successful in all patients.
      CONCLUSIONS: Psychoactive drugs should be prescribed cautiously in patients with
      known narrow angles and should be monitored by an ophthalmologist.

PMID- 8285897
TI  - Family history and risk of primary open angle glaucoma. The Baltimore Eye Survey.
AB  - OBJECTIVE: Primary open angle glaucoma has been previously associated with a
      positive family history of glaucoma. We used data from the Baltimore Eye Survey
      to examine this association. DESIGN: A population-based prevalence survey
      identified 161 cases of primary open angle glaucoma among 5308 black and white
      residents of east Baltimore, Md, who were 40 years of age or older. Family
      history was ascertained by interview and included all first-degree relatives
      (parents, siblings, and children). RESULTS: Age-adjusted associations of primary
      open angle glaucoma with a history of glaucoma were higher in siblings (odds
      ratio [OR] = 3.69) than in parents (OR = 2.17) or children (OR = 1.12). Odds
      ratios were slightly higher in blacks than in whites, and there was evidence of
      selection bias, with ORs between two and three times higher for those who had
      prior knowledge of their glaucoma diagnosis than for those who first received
      their diagnosis by the study examination (history in siblings OR = 4.72 for those
      with prior knowledge vs 2.77 for those without). CONCLUSION: Family history is an
      important risk factor for primary open angle glaucoma, although clinic-based
      studies are likely to overstate its impact.

PMID- 8285898
TI  - Clinicopathologic features of excised mitomycin filtering blebs.
AB  - Using light and electron microscopy, we examined two conjunctival filtering blebs
      that had been treated with mitomycin just prior to trabeculectomy and were later
      excised due to ocular hypotony. Light microscopy showed attenuated epithelium,
      loosely arranged subepithelial connective tissue, and scattered acute and chronic
      inflammatory cells. Electron microscopy also showed these findings and
      demonstrated the presence of presumably viable activated fibrocytes in the
      subepithelial connective tissue. The presence of inflammatory cells in the blebs
      was attributed to concurrent infections and suggests that mitomycin does not
      completely suppress, but may attenuate, the inflammatory response. The mechanism
      of hypotony and bleb failure in the two eyes was most likely a combination of
      over-filtration and a persistent wound leak due to a lack of postoperative
      subconjunctival fibrosis secondary to treatment with mitomycin.

PMID- 8285899
TI  - Sympathetic ophthalmia following laser cyclocoagulation.
AB  - We describe a 49-year-old white man with sympathetic ophthalmia following contact
      neodymium-YAG laser cyclotherapy. There was no invasive surgery, and no
      perforating injuries preceded cyclodestructive therapy. The eye had hemorrhagic
      secondary glaucoma due to Coats' disease. It was treated three times with contact
      cyclophotocoagulation after cyclocryotherapy failed to lower intraocular
      pressure. Subsequently, the intraocular pressure slowly decreased and the eye
      became phthisical 15 months after the last surgery. Intraocular inflammation
      developed in the fellow eye and sympathetic ophthalmia was suspected. Histologic
      and immunohistologic study of the enucleated blind eye confirmed this diagnosis.

PMID- 8285900
TI  - Is there evidence of an estrogen effect on age-related lens opacities? The Beaver
      Dam Eye Study.
AB  - OBJECTIVE: To evaluate a possible association between estrogen and lens
      opacities. DESIGN: A prevalence survey of age-related eye disease. SETTING:
      Beaver Dam, Wis. PARTICIPANTS: A total community sample of persons 43 through 84
      years of age at the time of a private census were recruited for examination,
      medical history, and photographs of the lenses of the eyes. Data from women are
      included in this report. MAIN OUTCOME MEASURES: Photographs were graded by
      protocol for the presence and severity of age-related lens opacities. RESULTS:
      Current use of postmenopausal estrogens was associated with a decreased risk of
      more severe nuclear sclerosis. Younger age at menarche was also associated with a
      protective effect regarding nuclear sclerosis. Older age at menopause was
      associated with a decreased risk of cortical opacities. CONCLUSION: These data
      are suggestive of a modest protective effect of estrogen exposure on the lenses
      of women. Further evaluation of this may be possible in studies currently under
      way in which postmenopausal estrogens are being tested for other (protective)
      effects.

PMID- 8285901
TI  - Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in
      a population.
AB  - OBJECTIVE: To investigate the relationship of various retinal lesions to systemic
      hypertension in the population-based Beaver Dam Eye Study. DESIGN: In this cross
      sectional population-based study, blood pressure was measured using standardized
      protocols. Using standardized protocols, stereoscopic color fundus photographs
      were graded in a masked fashion to determine the presence of retinopathy (defined
      as retinal microaneurysms only, blot hemorrhages only, hemorrhages and/or
      microaneurysms, cotton-wool spots, hard exudates, intraretinal microvascular
      abnormalities, venous beading, and retinal new vessels), retinal arteriolar
      narrowing, and arteriovenous nicking. PARTICIPANTS: Subjects aged 43 through 84
      years who lived in Beaver Dam, Wis, between 1987 and 1988 were examined between
      1988 and 1990. People with diabetes or retinal vascular occlusions were excluded.
      RESULTS: Retinopathy was present in 336 subjects (7.8%), arteriolar narrowing in
      582 subjects (13.5%), and arteriovenous nicking in 95 subjects (2.2%) in the
      nondiabetic population. Hypertension was associated with increased frequency of
      retinopathy, arteriolar narrowing, and arteriovenous nicking. After adjusting for
      age, hypertension was associated with the presence of retinopathy (in men:
      relative risk [RR], 1.47; 95% confidence interval [CI], 1.10 to 1.96; in women:
      RR, 1.69; 95% CI, 1.26 to 2.27), arteriolar narrowing (in men: RR, 1.34; 95% CI,
      1.03 to 1.74; in women: RR, 1.37; 95% CI, 1.14 to 1.64), and arteriovenous
      nicking (in men: RR, 1.87; 95% CI, 0.99 to 3.54; in women: RR, 1.65; 95% CI, 1.00
      to 2.73). Retinopathy, arteriolar narrowing, and arteriovenous nicking were more
      frequent in those subjects whose blood pressure was elevated despite use of
      antihypertensive medications compared with those subjects whose blood pressure
      was controlled with antihypertensive medications or those who were normotensive.
      CONCLUSIONS: These data suggest that retinopathy and retinal arteriolar narrowing
      are common in people with hypertension. Further longitudinal study is necessary
      to evaluate the public health significance of these retinal lesions regarding
      possibly increased risk of renal and cardiovascular disease.

PMID- 8285902
TI  - Teaching surgeons to stitch.

PMID- 8285903
TI  - Resuscitation following injury: an end or a means?
AB  - It is known that a successful outcome after injury requires haemostasis and
      replacement of intra- and extracellular fluid losses. In situations of controlled
      haemorrhage rapid replacement of these fluid losses is likely to be associated
      with the least morbidity. When considering uncontrolled haemorrhage, however,
      there is good evidence that effective resuscitative devices and strategies have
      proven to be associated with a worse outcome when used initially than when their
      use follows surgical control of bleeding. Despite newer developments in
      resuscitative technique, surgeons must continue to be involved in the early
      management of the severely injured so that they are in the best position to
      employ their skills and provide surgical haemostasis when and where it is
      required. The 'end' therefore in resuscitation of the injured is a normovolaemic,
      normotensive patient who is physiologically stable and able to have definitive
      management of his/her anatomic injuries. The 'means' are good prehospital care,
      accurate initial assessment and resuscitation that employs temporary and
      definitive haemostasis combined with adequate volumes of appropriately chosen and
      delivered resuscitation fluid.

PMID- 8285904
TI  - Discogenic compression of the cauda equina: a surgical emergency.
AB  - The syndrome of cauda equina compression due to central disc rupture is uncommon
      but its importance greatly transcends its rarity. Key symptoms and signs are
      bilateral leg pain, weakness or numbness (although unilateral symptoms or even
      absence of leg pain do not exclude the diagnosis), perineal numbness and, in 60%
      of patients, bladder and bowel incompetence ranging from dysuria to vesical and
      anal sphincter paralysis. Diagnosis and treatment are often delayed due to lack
      of recognition of the condition and failure to appreciate the surgical imperative
      for its treatment. At the present time myelography is the one essential
      investigation, although this may become supplanted in time by magnetic resonance
      imaging. Arrangements for myelography should be planned so that immediate
      operation can be commenced following the procedure. The onset of disc rupture may
      be acute and massive and result in intradural sequestration of disc fragments in
      7.5% of cases. Intradural exploration and/or transdural sequestrectomy avoids
      traction on already compromised nerve roots and is often safer than extradural
      sequestrectomy. The onset of bladder paralysis is a most important indication for
      immediate surgery. The cases presented show that there is a highly significant
      difference in the outcome of those cases operated on within 24h of bladder
      paralysis compared to those operated on after this period.

PMID- 8285905
TI  - Missed injuries in the multiply traumatized.
AB  - The delayed diagnosis of injuries in traumatized patients is a recognized
      problem. A retrospective review of trauma patients admitted to a major teaching
      hospital has been performed. The records of all patients admitted to the
      intensive care unit (ICU) have been checked to determine the incidence of late
      diagnosed injuries. The notes written by the staff of the emergency department
      and the ICU, and the attending surgical registrars have been used as the criteria
      of initial diagnosis. Comparing them to the injuries listed in the progress
      notes, investigation reports, discharge summary and follow-up outpatient notes
      led to the discovery of a number of missed injures (19 of 50 patients had one or
      more). In 4 cases the management involved further surgery due to new diagnoses.
      This is consistent with overseas literature. A review of the literature is
      presented and methods to improve the missed diagnosis rate are discussed.

PMID- 8285906
TI  - Value of the prospective 'before and after' study as a methodology to evaluate
      outcome in a trauma centre.
AB  - A series of interventions (administrative, clinical and educational) was
      introduced to improve the quality of trauma care at Royal Prince Alfred Hospital,
      the designated trauma centre for the Central Sydney Area Health Service (CSAHS).
      A prospective, 'before and after' study was conducted to assess changes in
      outcome following the introduction of these measures. The trauma centre survival
      rate for patients admitted with serious injury (Injury Severity Scores > 15)
      increased significantly, from 72% in the nine months before trauma centre
      designation to 89% in the nine months after (P = 0.005). The peer review
      designated, potentially avoidable death rate did not change significantly over
      the two study periods, remaining in the 20-30% range. Similarly the unexpected
      death rate (TRISS) did not change significantly, remaining in the 20-45% range. A
      trend to a lower trauma centre mortality in those arriving with a systolic blood
      pressure < or = 90 mmHg was noted. Seven out of 14 patients 'at risk' from
      exsanguination died in the first 9 months compared with one out of seven in the
      second 9 months (P = 0.17). An unexpected finding was a change in the degree of
      injury severity and physiological status in patients arriving at the trauma
      centre. The Injury Severity Scores were significantly lower (P = 0.008) and the
      Revised Trauma Scores significantly higher (P = 0.0006) in the latter 9 months of
      the study. It was concluded that the improved trauma centre survival rate was a
      reflection of a reduced hospital mortality from haemorrhagic shock in conjunction
      with a lesser degree of injury severity in patients admitted from the CSAHS.

PMID- 8285908
TI  - The morbidity of surgical access: a study of open versus laparoscopic
      cholecystectomy.
AB  - A prospective non-randomized study of 37 adult patients undergoing open
      cholecystectomy and 40 patients undergoing laparoscopic cholecystectomy was
      undertaken to test the hypothesis that surgical access alone has a significant
      impact on postoperative morbidity. Specifically the study examined the
      deterioration of pulmonary function, development of pulmonary complications,
      postoperative narcotic requirement and total bed stay as markers of postoperative
      morbidity. The results showed that significantly less deterioration of pulmonary
      function occurred in patients treated using the laparoscopic approach. In this
      group there was also significantly less requirement for postoperative narcotics,
      less consequent development of pulmonary complications and a shorter bed stay in
      hospital. The study documents the substantial impact of surgical access on
      postoperative morbidity and highlights the benefits of the laparoscopic 'minimal
      access' approach.

PMID- 8285907
TI  - Postoperative fatigue after laparoscopic surgery.
AB  - Postoperative fatigue (POF) appears to be less following laparoscopic surgery but
      this has not been proven previously. This study compared a group of patients who
      had undergone open cholecystectomy with a group undergoing laparoscopic
      cholecystectomy. Postoperative fatigue was found to be decreased in duration in
      the patients having laparoscopic surgery, returning to pre-operative fatigue
      levels by 14 days, compared to 28 days for open surgery. Postoperative pain in
      the first 24 h and the early metabolic response to surgery were similar for both
      groups. The authors conclude that laparoscopic surgery is associated with
      decreased POF and that this is unlikely to be accounted for by a decrease in the
      early metabolic response to surgery.

PMID- 8285909
TI  - A technique for cholangiography during laparoscopic cholecystectomy.

PMID- 8285910
TI  - Post-traumatic radio-ulnar synostosis treated by surgical excision and adjunctive
      radiotherapy.
AB  - The management of three cases of traumatic radio-ulnar synostosis involved
      surgical excision of the synostotic bone followed by radiotherapy. Irradiation
      was commenced on the first postoperative day and was continued daily. The first
      patient received 20 Gy midline in 10 fractions and the second and third patients
      10 Gy in five fractions. No acute side effects were observed. All three patients
      regained a good, functional range of forearm rotation with no evidence of
      recurrence of the synostosis after 2 years. This method of treatment is
      recommended as an alternative to other adjunctive therapies including
      interposition of material such as silicone sheet between the bones or peri
      operative pharmacological suppression.

PMID- 8285911
TI  - Adolescent breast maldevelopment: buying time with liposuction.

PMID- 8285912
TI  - Cervical epidural haematoma following minor trauma.
AB  - Cervical epidural haematoma following minor trauma is unusual in normal adults.
      It is important that the condition is diagnosed and treated promptly in order to
      improve the prognosis. Surgery to evacuate the haematoma is the treatment of
      choice.

PMID- 8285913
TI  - The role of coherence time in the effect of microwaves on ornithine decarboxylase
      activity.
AB  - Previously, we demonstrated the requirements for a minimum coherence time of an
      applied, small amplitude (10 microT) ELF magnetic field if the field were to
      produce an enhancement of ornithine decarboxylase activity in L929 fibroblasts.
      Further investigation has revealed a remarkably similar coherence time phenomenon
      for enhancement of ornithine decarboxylase activity by amplitude-modulated 915
      MHz microwaves of large amplitude (SAR 2.5 W/kg). Microwave fields modulated at
      55, 60, or 65 Hz approximately doubled ornithine decarboxylase activity after 8
      h. Switching modulation frequencies from 55 to 65 Hz at coherence times of 1.0 s
      or less abolished enhancement, while times of 10 s or longer provided full
      enhancement. Our results show that the microwave coherence effects are remarkably
      similar to those observed with ELF fields.

PMID- 8285914
TI  - Effects of time-varying uniform magnetic fields on natural killer cell activity
      and antibody response in mice.
AB  - Natural Killer cell activity and antibody response were studied in Balb/c mice
      which were exposed in vivo to uniform pulsed magnetic fields (square-wave, 0.8
      Hz, 120 mT maximum field strength, 0.1 s rise-time) for 5 days, 10 h/day. No
      effects were found in antibody response to sheep red blood cell (SRBC)
      immunization as assayed by counting the plaque-forming cells (PFC) in the spleens
      of animals on the sixth day. Following 5-day exposures, the activity of Natural
      Killer (NK) cells was measured in vitro by challenge with YAC-1 cells, in
      experiments in which mice were not immunized. An increase of NK cytotoxic
      activity due to exposure was found which depended on the age of the mice (effect
      observed above 12 weeks) and on the strength of the applied field (effect
      observed above 30 mT).

PMID- 8285915
TI  - A scheme for incorporating DC magnetic fields into epidemiological studies of EMF
      exposure.
AB  - Experimental data on calcium-ion release in chicken brain tissue suggest that
      biological effects of electric and magnetic fields (EMFs) are concentrated near
      certain "active combinations" of DC magnetic field strength and "effective" AC
      magnetic field frequencies. We hypothesize that active AC/DC combinations may
      exist and suggest that epidemiologic data, coupled with DC magnetic field
      measurement, may be used to identify critical exposure conditions. An empirical
      model is used to calculate these multiple active combinations at any given DC
      magnetic field strength and to define a rating system that incorporates the
      proximity of AC magnetic field frequencies generated by electric power lines to
      the new, computed effective frequencies. Such an exposure score may be useful in
      investigating correlations of EMF exposure with disease incidence. For 60 Hz and
      50 Hz, the highest EMF exposure scores occurred at DC field strengths of 506 mG
      and 422 mG, respectively. The exposure score contains a factor which may be
      adjusted to reflect the importance of harmonics of the AC magnetic field as well
      as of the fundamental frequency. Using this factor, we consider two important
      special cases consistent with chick brain data: 1) we consider active pairs
      associated with all detectable harmonics (up to 660 Hz) without regard to
      relative intensity of the harmonics, and 2) we use the relative intensities of
      the AC field frequencies to adjust their contribution to the exposure score.

PMID- 8285916
TI  - Temporal bisection in rats: the effects of high-peak-power pulsed microwave
      irradiation.
AB  - The effects of high-peak-power, pulsed microwaves on a time perception and
      discrimination task were studied in rats. Exposures were performed with the TEMPO
      exposure system, which produces an 80 nanosecond pulse with peak-power levels in
      excess of 700 megawatts. The ability to expose animals to such fields within a
      controlled environment is unique. As determined by calorimetry, a maximal, whole
      body-averaged, specific-absorption rate of 0.072 W/kg was produced. Thus
      exposures were well below a recommended SAR limit of 0.4 W/kg. Power levels of
      transmitted microwaves were varied over a 50 dB range to obtain ascending and
      descending dose-response functions for each of the behavioral measures. Measures
      of time perception, response bias, and total trials did not change with power
      level. Dose-response effects were observed for discriminability (ability to
      distinguish between durations), session time, and trial completions (null
      responses, failures to respond on a trial). Covarying sound and X-ray exposures
      produced by TEMPO did not reliably correlate with the observed microwave effects.
      The observation of repeatable dose-response effects on discriminability and null
      responses indicates that the microwave exposures were affecting cognitive
      function in the rats, particularly the decision-making process.

PMID- 8285917
TI  - Biologic effects of prolonged exposure to ELF electromagnetic fields in rats. I.
      50 Hz electric fields.
AB  - A three-year investigation was conducted on the biological effects of high
      intensity electric field exposures of rats for up to 18% of their life span. Two
      hundred and forty adult male rats, divided into groups of 20 animals each, were
      exposed at ground potential for 8 h/day at 25-kV/m and 100-kV/m 50-Hz electric
      fields or were sham exposed for 280, 440, and 1240 h. The corresponding ages at
      sacrifice were 140, 164, and 315 days. An additional group of 40 rats was
      investigated under similar experimental conditions after 440 h of exposure at
      floating potential. Independent of exposure duration, mode of grounding, and
      field strength, no statistical differences in body weight, morphology, and
      histology of the liver, heart, mesenteric lymph nodes, and blood variables
      (hematology and serum chemistry) were found in comparison with sham-exposed
      animals. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone
      (FSH), and testosterone (TS) at sacrifice varied widely among experimental
      animals in the same group but did not differ in exposed compared with sham
      exposed rats. A nonsignificant tendency toward a decrease in the testes/body
      weight ratio was found after 1240 h of exposure. Microscopic examination of a
      large number of specimens showed no quantitative or qualitative statistical
      differences in testes alterations either among exposed animals or between exposed
      and their corresponding sham-exposed groups. We conclude that 50-Hz electric
      field exposure, even of long duration at very high field strengths, does not
      induce harmful effects on tissues with high cellular turnover rates and does not
      impair the reproductive function of rats. Moreover, after exposure, all variables
      investigated were well within the normal physiological range.

PMID- 8285918
TI  - [Reactions of 4/6-amide-lactam function of nucleic bases].
AB  - Reactivity of the amide-lactam function of nucleic bases under various
      conditions, methods of its activation, protection, deprotection and modification
      have been considered. Expediency of the function's protection in oligonucleotide
      synthesis is discussed.

PMID- 8285919
TI  - [Primary structure and catalytic properties of extracellular ribonuclease from
      Bacillus circulans].
AB  - A comparative research of individual peptide structures obtained after
      hydrolysing of Bacillus circulans and B. amyloliquefaciens RNases by the Glu
      specific staphylococcal protease was carried out by means of mass-spectrometry
      and Edman degradation methods. A complete amino acid sequence of B. circulans
      RNase was determined. Gln15, Gly65 and Gln104 residues in B. amyloliquefaciens
      RNase were found to be substituted by Leu, Ala and Lys residues in B. circulans
      RNase, respectively. Catalytic properties of the B. circulans RNase in
      transesterification reactions with poly- and oligonucleotides as substrates were
      investigated.

PMID- 8285920
TI  - [Isolation and properties of site-specific endonuclease BspTS514I from the
      thermophilic bacteria Bacillus species TS514].
AB  - New site-specific endonucleases BspBS31I, BstBS32I, BspIS41, BstTS5I, BspTS514I
      were isolated from five thermophilic soil bacteria Bacillus sp. BS31, B.
      stearothermophilus BS32, Bacillus sp. IS4, B. stearothermophilus TS5, Bacillus
      sp. TS514. The enzymes are isoschizomers of the restriction endonuclease BbvII.
      Endonuclease BspTS514I was obtained pure from interfering contaminations by two
      consecutive chromatographies on blue agarose and hydroxyapatite. The enzyme
      exhibits a maximal activity at 55 degrees C in 10 mM tris-HCl (pH 9.2), 10 mM
      MgCl2 and 50 mM NaCl.

PMID- 8285921
TI  - [Anticholinesterase activity of certain carboranyl-containing thio- and
      selenoesters of pentavalent phosphorus acids].
AB  - Anticholinesterase activity of carboranyl containing thio- and selenoesters of
      pentavalent phosphorus acids has been studied. Insertion of the carboranyl
      substituents in the thioester group of phosphororganic compounds was found to
      increase the anticholinesterase activity as compared with the thioalkyl
      analogues. The compounds with B-carboranyl group are less active inhibitors of
      cholinesterase than their isomers with C-carboranyl group.

PMID- 8285922
TI  - [Subtractive hybridization. Theoretical analysis, and a principle of the trap].
AB  - An analysis of the kinetics of the subtractive hybridization and the extent of
      enrichment of sequence differences between two otherwise identical genomes or
      transcripts has been carried out for different conditions. The hybridization of
      single- or double-stranded DNA (tracer) containing the difference (target) to the
      large excess of single-stranded complementary DNA not having the sequence
      (driver) gives a much higher enrichment of the target than hybridization of
      double-stranded driver and tracer or double-stranded driver with single-stranded
      tracer. The conclusion is that the first approach can give means for efficient
      extraction of the target without artificial simplifications of the genomes before
      subtraction. A principle of the "trapper", preventing the hybrids formed from
      dissociation in the course of PCR amplification of the target enriched, is
      proposed as a complement to the single-stranded DNA hybridization in the process
      of highly efficient subtraction.

PMID- 8285923
TI  - [Synthesis of thioacetamide analogs of blood group specific trisaccharide A and
      its fragments].
AB  - The determinant trisaccharide of the blood group A, GalNAc alpha 1-3(Fuc alpha 1
      2)Gal beta, was modified by treatment of the trisaccharide acetate with
      phosphorus pentasulphide to convert its acetamide fragment determining the
      serological difference between antigenic determinants A and B into the
      thioacetamide derivative. Thionated analogues of the A disaccharide and of GalNAc
      alpha-glycoside were obtained in a similar way. Interaction of three monoclonal
      anti-A antibodies with modified antigens was studied using ELISA, the O-->S
      replacement allowing to evaluate the contribution of the acetamido carbonyl group
      into the antigen-antibody interaction.

PMID- 8285924
TI  - [Formation of a structural isomer of platelet activating factor during
      acetylation of 1-alkyl-sn-glycero-3-phosphocholine].
AB  - In studying acetylation of 1-alkyl-sn-glycero-3-phosphocholine (lyso PAF) with
      acetic anhydride, a key step of the platelet activating factor (PAF) synthesis,
      we have found that in the presence of triethylamine or 4-dimethylaminopyridine
      some 1-alkyl-3-acetyl-sn-glycero-2-phosphocholine as an admixture to PAF formed,
      whereas the acid catalysed reaction resulted in isomerically pure PAF. The
      mechanism of the reaction leading to the PAF structural isomer is discussed.

PMID- 8285925
TI  - [Synthesis of monoepoxides of arachidonic, eicosapentaenoic, and docosahexaenoic
      acids].
AB  - A practical synthesis of cis-monoepoxides from free arachidonic 20:4 (n-6),
      eicosapentaenoic 20:5 (n-3) and docosahexaenoic 22:6 (n-3) acids, their
      cytochrome P-450 epoxygenase metabolites, is described. The free polyunsaturated
      fatty acids (PUFA) were oxidized each by 1.25 eq. m-chloroperbenzoic acid in
      ethanol to give a mixture of PUFAs' mono-epoxy derivatives (45%) which was
      separated by HPLC and the individual isomers were characterised by mass
      spectrometry. All regioisomers of the free PUFAs' cis-monoepoxides were thus
      obtained.

PMID- 8285926
TI  - [Synthesis and antigenic activity of peptides from the C-terminal part of the NS4
      protein of the hepatitis A virus].
AB  - A set of four peptides from the HCV NS4-protein C-terminal region (aa 1921-1940)
      were obtained by solid-phase synthesis using activated esters and symmetrical
      anhydrides of Boc-amino acids. Peptide 1921-1940 has demonstrated a positive
      reaction in ELISA with individual anti-HCV-positive sera from patients with acute
      and chronic hepatitis C (80% and 56%, respectively). We analysed the antigenic
      properties of the peptide 1921-1940 and its fragments and suggested at least two
      antibody recognizing sites to be contained in this region.

PMID- 8285927
TI  - Early administration of nifedipine in suspected acute myocardial infarction. The
      Secondary Prevention Reinfarction Israel Nifedipine Trial 2 Study.
AB  - BACKGROUND: The administration of nifedipine, 30 mg/d, between 7 and 22 days
      after hospitalization for an acute myocardial infarction (Secondary Prevention
      Reinfarction Israel Nifedipine Trial study) showed no effect on subsequent
      mortality and morbidity. Since a possible indication of benefit was observed in
      patients with a second- or higher-order infarction, a second trial was conducted
      with a higher dose (60 mg/d), early administration (usually within 3 hours of
      hospital admission), and in high-risk patients only. METHODS: A total of 1358 men
      and women with suspected acute myocardial infarction (MI), judged not to require
      calcium antagonist therapy, were randomized to receive nifedipine, 60 mg/d, or
      placebo between November 1985 and July 1986. Study medication was discontinued in
      352 patients because they did not exhibit study criteria for MI or lacked high
      risk criteria, or because they decided to discontinue the study. Thus, the
      treated high-risk group included 1006 patients, of whom 826 were successfully
      titrated to the target dose of 60 mg/d and were treated for up to 6 months.
      RESULTS: In the 1006 patients, mortality was 18.7% among those randomized to
      nifedipine and 15.6% in the patients randomized to placebo. This reflected an
      increased mortality of 7.8% as compared with 5.5% during the first 6 days in the
      nifedipine and placebo groups, respectively (adjusted mortality odds ratio by
      logistic regression, 1.60; 95% confidence interval, 0.86 to 3.00). Among the 826
      patients who continued treatment, mortality was equal in the nifedipine (9.3%)
      and placebo (9.5%) groups. No differences in the rates of nonfatal MI (5.1% and
      4.2% in the nifedipine and placebo groups, respectively), hospitalization due to
      unstable angina, and frequency of chest pain reported during follow-up were
      observed. An increased rate of sudden death (4.9%) in the placebo group in
      comparison with the nifedipine group (2.3%) was not statistically significant on
      post hoc testing, nor was an effect of nifedipine demonstrable in post hoc
      analyses by congestive heart failure status of randomized patients. CONCLUSION:
      Nifedipine as a prophylactic treatment in patients immediately after acute MI or
      in survivors recovering 1 week or longer after acute MI appears ineffective.
      Early routine administration of nifedipine in acute MI, other than to patients in
      whom it may be specifically indicated (eg, those with Prinzmetal's variant angina
      or severe hypertension) may be hazardous and seems to be contraindicated.

PMID- 8285928
TI  - Pain, euthanasia, and anesthesiologists.

PMID- 8285929
TI  - A preliminary report comparing magnetic resonance coronary angiography with
      conventional angiography.
AB  - BACKGROUND: The ability to assess the patency of coronary arteries by noninvasive
      means would represent an important advance. We have developed a magnetic
      resonance imaging (MRI) coronary angiographic technique that permits the display
      of areas of abnormal coronary blood flow. We have compared this method with
      conventional contrast angiography for the identification of coronary-artery
      stenoses. METHODS: MRI coronary angiography was performed with an
      electrocardiographically gated sequence in 39 subjects, 33 to 84 years of age,
      who were scheduled for elective cardiac catheterization with coronary
      angiography. Sequential overlapping transverse and oblique sections were acquired
      during periods of breath-holding and were displayed as cine loops for analysis.
      MRI and conventional angiographic data were compared in a blinded manner. The
      four major epicardial coronary arteries were classified by MRI coronary
      angiography as being normal (or having only minimal irregularities) or as having
      disease that was moderately severe to severe. RESULTS: The sensitivity and
      specificity of MRI coronary angiography, as compared with conventional
      angiography, for correctly identifying individual vessels with > or = 50 percent
      angiographic stenoses were 90 percent and 92 percent, respectively. The
      corresponding positive and negative predictive values were 0.85 and 0.95,
      respectively. The sensitivity and specificity of the technique were 100 percent
      and 100 percent, respectively, for the left main coronary artery, 87 percent and
      92 percent for the left anterior descending coronary artery, 71 percent and 90
      percent for the left circumflex coronary artery, and 100 percent and 78 percent
      for the right coronary artery. CONCLUSIONS: MRI coronary angiography provides a
      new approach to evaluating the patency of coronary arteries. These preliminary
      data suggest that this technique may provide a noninvasive means of evaluating
      patients with known or suspected coronary artery disease. At its current stage of
      development, this procedure may be most helpful for excluding clinically
      important stenoses in patients referred for diagnostic contrast angiography.

PMID- 8285930
TI  - Counselling in general practice.

PMID- 8285931
TI  - Counselling in general practice.

PMID- 8285932
TI  - Deception in research, and racial discrimination in medicine.

PMID- 8285933
TI  - G protein-linked receptors labeled by [3H]histamine in guinea pig cerebral
      cortex. I. Pharmacological characterization [corrected].
AB  - Binding of histamine to washed membranes from guinea pig cerebral cortex can be
      described empirically as two classes of distinct and independent sites (log IP1 =
      -8.45 +/- 0.02, R1;t = 98 +/- 6 pmol/g of protein; log KP2 = -6.34 +/- 0.22, R2.t
      = 990 +/- 60 pmol/g of protein). At 1.4 nm [3H]histamine, the kinetics of
      association and dissociation are biexponential. The values of k-Pj/k+Pj
      calculated for parallel one-step processes agree well with the corresponding
      values of KPj. Both k-p1 and k-P2 are increased by 0.1 mM
      guanylylimidodiphosphate; apparent capacity at equilibrium is reduced for both
      classes of sites, with little or no change in KP1 or KP2. Twenty-six H2 and H3
      agonists and antagonists block access of [3H]histamine to the same sites, and the
      binding patterns reveal either one or two hyperbolic terms [i.e., sigma nj = 1 F'
      jKj/(Kj+[L])]. Two terms are required for six agonists and six antagonists, and
      F'2 varies widely from ligand to ligand. Also, the quantity log (K2/K1) is
      correlated with F'1 among agonists but with F'2 among antagonists (K1 < K2). The
      pharmacological selectivity is suggestive of both H2 and H3 receptors. An H2
      specificity emerges from the appropriate values of Kj for 12 H2 agonists (i.e.,
      K1 when n = 1 and K2 when n = 2; p = 0.00045), although a specificity distinct
      from that of H2 receptors is found with H2 antagonists. An H3 specificity emerges
      from the inhibitory potencies (IC50) of eight H3 agonists (p = 0.00025) and eight
      H3 antagonists (p = 0.0019); also, the sites labeled by [3H]histamine resemble H3
      receptors reportedly labeled by N alpha-[3H]methylhistamine and (R)-alpha
      [3H]methylhistamine. Ligand-dependent differences in F'2 are inconsistent with
      the notion of distinct and independent sites, and the tendency of antagonists to
      promote the sites of weaker affinity (F'2) argues against a ligand-regulated
      equilibrium between two states. The physical significance of the binding
      parameters is therefore unclear. The failure to identify an unambiguous
      pharmacological specificity may reflect the failure to assess binding in the
      correct mechanistic context.

PMID- 8285934
TI  - Hysterical conversion and developmental psychiatry.

PMID- 8285935
TI  - Assessing secondary malignancy risk.

PMID- 8285936
TI  - Racial discrimination against doctors.

PMID- 8285937
TI  - Condom characteristics: the perceptions and preferences of men in the United
      States.
AB  - Perceptions regarding the consequences of condom use, as well as preferred
      characteristics of condoms, are examined in a nationally representative sample of
      3,321 men aged 20-39. The psychological and interpersonal effect most often cited
      is that using a condom "shows that you are a concerned and caring person." This
      is particularly the case among black men and men who are young and have low
      educational attainments. However, the same men usually agree that using a condom
      sends unwanted messages to one's partner--for example, that doing so "makes your
      partner think that you have AIDS" and "shows that you think that your partner has
      AIDS." In contrast, white men and those who are highly educated tend to cite
      embarrassment when buying condoms as a frequent consequence of condom use. The
      device-related consequences cited most often, particularly among black,
      unmarried, young and poorly educated men, are that using a condom results in
      reduced sensation, that one must be careful during sex or the condom may break
      and that one must withdraw quickly after sex or the condom may come off. When
      purchasing condoms, most men look for those that are easy to put on, have the
      right amount of lubrication and stay on; these preferences are particularly
      prevalent among black men. Few men identify color, ribbing and partner's
      preference for condom type as important.

PMID- 8285938
TI  - Acute myocardial infarction experience at a rural hospital.

PMID- 8285939
TI  - Keratometry using the Goldmann tonometer.
AB  - Keratometry using the Goldmann tonometer is a reliable and readily available
      guide to corneal astigmatism following cataract surgery. In regular corneal
      astigmatism the Goldmann tonometer rings are distorted into skewed ellipses. The
      axis of the cylinder can be measured by rotating the tonometer head until an
      undistorted ellipse is obtained. The power is then assessed by comparison with
      standard ellipses. The difference in the intracular pressure readings (mmHg) in
      the two principal meridians was also a good guide to the presence of astigmatism.
      Goldmann keratometry was performed by a single masked observer in 71 patients 8
      weeks after routine extracapsular cataract surgery. This was compared with Javal
      Schiotz Keratometry performed by an independent observer. In 83% of patients the
      axis was measured to within 20 degrees. The 95% confidence interval for the power
      was +/- 2.90 DC; and 87% of patients would have sutures removed appropriately.

PMID- 8285940
TI  - [Incentives].

PMID- 8285941
TI  - Changes in outer membrane protein of Salmonella typhimurium due to copper
      resistance plasmid.

PMID- 8285942
TI  - Occupational overuse syndrome.

PMID- 8285943
TI  - NSAIDS in the postoperative period. Don't dismiss gastric erosion.

PMID- 8285944
TI  - Potential of trypanotolerance as a contribution to sustainable livestock
      production in tsetse affected Africa.
AB  - Tsetse transmitted trypanosomiasis is possibly the major constraint on livestock
      and agriculture development in Subsaharan Africa. Control of the disease has been
      based on vector control as well as on the use of trypanocidal drugs to treat or
      prevent infection in animals. Both control methods are effective but have proven
      not to be sustainable. Moreover, the development of a vaccine against
      trypanosomiasis is unlikely to be successful in the near future. On the other
      hand, trypanotolerant cattle, like the N'Dama can survive and produce in tsetse
      affected areas without interventions. This taurine breed has been indigenous to
      Africa for approximately 7,000 years and forms presently about 6% of the bovine
      population of Africa. Generally the N'Dama are kept in the rural areas by the
      small-scale farmer as a multi-purpose animal. Recent studies have defined
      management characteristics and assessed the production potential at the village
      level and under ranching conditions of N'Dama cattle exposed to various levels of
      tsetse challenge. Furthermore, experimental infections showed conclusively the
      superior resistance to the effects of infection of the N'Dama cattle when
      compared to zebu cattle and have confirmed that trypanotolerance is innate in
      N'Dama cattle. Studies have been conducted on development of protective humoral
      and cellular responses, the regulation of parasite multiplication and control of
      anaemia. These studies provided tools for identifying components of
      trypanotolerance. The ability to resist the development of anaemia in the face of
      infection, has shown to be correlated with the capacity to be productive;
      moreover, PCV values can serve as selection criterium for trypanotolerance.
      Subsequently, repeatabilities and heritabilities of trypanotolerance and
      performance traits were estimated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285945
TI  - Hippocampal gamma-aminobutyric acid and benzodiazepine receptors after early
      phenobarbital exposure.
AB  - Mice were exposed to phenobarbital (PhB) prenatally (PreB offspring) by feeding
      their mothers 3 g/kg PhB in milled food on gestation days 9-18, or neonatally by
      directly injecting pups of intact mothers with daily dose of 50 mg PhB on
      postnatal days 2-21 (NeoB offspring). At age 22 or 50 days, the offspring were
      tested for gamma-aminobutyric acid (GABA) up take in the hippocampus and in the
      rest of the brain. In addition, [3H]muscimol and [3H]flunitrazepam binding in the
      hippocampus and cortex were measured in the offspring at age 22 and 50 days. Long
      term decrease in GABA uptake was found in the NeoB group. A 23% decrease was
      found in 22-day-old mice (P < 0.001) and a 22% decrease in 50-day-old mice (P <
      0.05). In addition, there was a 22% decrease in GABA uptake in the brain of 22
      day-old PreB mice (P < 0.05). An increase of 52% in [3H]muscimol binding (P <
      0.001) and 45% (P < 0.001) in [3H]flunitrazepam binding were measured in the
      hippocampus in the 22-day-old NeoB mice; no differences were found in affinity.
      The differences were short-term and could no longer be detected at age 50 days.
      No differences were found in the cortex; unlike NeoB, PreB mice did not differ
      from controls. The results suggest upregulation of the GABAergic system in early
      PhB exposed mice.

PMID- 8285946
TI  - Shorter treatment courses or larger daily doses?

PMID- 8285947
TI  - The use of documents for computer-based patient records.

PMID- 8285948
TI  - Diaphragmatic pacing. An option for patients with quadriplegic respiratory
      paralysis.
AB  - Recent advances in design, increased reliability, and computerized pacing provide
      an exciting alternative to mechanical ventilation for the quadriplegic patient.
      Research into the development of totally implantable, demand-type respiratory
      pacemakers is ongoing. Careful patient selection, meticulous surgical technique,
      adequate training in the use of the device, and conscientious follow-up
      contribute to a successful outcome--increased mobility and independence for the
      ventilator-dependent quadriplegic patient.

PMID- 8285949
TI  - Urinary oligosaccharides in pregnant or lactating women: pitfall in screening.

PMID- 8285950
TI  - Patient evaluation of four different combinations of intravenous anaesthetics for
      short outpatient procedures.
AB  - We studied 200 female patients (ASA group 1) scheduled for termination of
      pregnancy under general anaesthesia. The patients were randomly allocated to
      receive one of four anaesthetic combinations; (1) propofol in combination with
      ketamine 20 mg, (2) propofol in combination with fentanyl 0.1 mg, (3) thiopentone
      in combination with fentanyl 0.1 mg, (4) methohexitone in combination with
      fentanyl 0.1 mg. All patients were breathing oxygen in nitrous oxide 1:2.
      Patients' self assessments of per- and postoperative course and time to discharge
      were compared. No patient's response suggested light anaesthesia, but dreams were
      frequently experienced during anaesthesia especially among the propofol-ketamine
      combination (29 out of 50). Time to discharge was shortest for the groups of
      patients given propofol; the mean time was 93 and 96 min for the ketamine and
      fentanyl groups respectively. During the recovery period significantly more
      patients experienced pain in the ketamine-propofol group. Complaints of nausea
      were seen in only 15 patients, and seven patients noted psycho-mimetic side
      effects during recovery, without any differences between the groups. All four
      combinations tested offered good conditions for short outpatient procedures.
      However, the propofol-fentanyl combination was found to offer the best quality of
      anaesthesia as assessed by the patients themselves.

PMID- 8285951
TI  - Reproducibility of fluorine-18-6-fluorodopa positron emission tomography in
      normal human subjects.
AB  - Fluorine-18-6-fluorodopa (FD) positron emission tomography (PET) is established
      for measuring nigrostriatal dopaminergic function. This is despite the absence of
      data on the reproducibility of results. METHODS: With an ECAT 953B/31 tomograph,
      we performed two or three repeated FD PET scans in 10 normal subjects to measure
      the scan-to-scan variation in the total striatal uptake rate constant (Ki).
      RESULTS: We found a scan-to-scan standard deviation (s.d.) of 8.7% of the mean.
      The between-subject s.d. was 26% of the mean, resulting in a reliability
      coefficient of 90%. Analysis of the variation in the components contributing to
      Ki showed a reliability varying from 77% to 86% (depending on the different time
      points analyzed) for emission data measured by the PET camera. The reliability of
      the blood radioactivity time course, as reflected by the stretch time, varied
      from 43% to 81%. The overall reliability for the correction of the blood time
      course for metabolites of FD was 71%. Variation in the blood radioactivity
      contributed to the variability of Ki by 50% more than the metabolite correction
      and by 200% more than the emission data. CONCLUSION: The striatal Ki is a
      reliable measurement; it has a 95% chance of lying within +/- 18% of its value
      for an individual normal subject.

PMID- 8285952
TI  - Development of the emergency physician job satisfaction measurement instrument.
AB  - The objective of this study was to develop a valid and reliable instrument to
      measure the job satisfaction of physicians practicing emergency medicine. A
      prospective survey involving four separate stages (an item evaluation and
      reduction stage, a factor analysis stage, a construct validity stage, and a
      reliability stage) was distributed in Canada to full-time emergency physicians.
      Three separate survey instruments were administered (an initial draft instrument
      with 228 items, a pilot instrument with 142 items, and the final instrument with
      79 items). Construct validity of the final instrument was tested by evaluating
      the correlation between physician scores on the instrument, and scores on two
      instruments measuring the same construct, and three measuring different but
      related constructs. A draft instrument with 228 items and six hypothetical
      domains was tested on 61 physicians. Evaluation for frequency endorsement,
      redundancy, and homogeneity reduced the item pool to 157. The remaining 157 items
      were used as a pilot instrument and tested on 223 physicians. Factor analysis
      eliminated 66 items from the pilot instrument, creating a final instrument with
      79 items, 11 factors, and six domains. Cronbach's coefficient alpha for the final
      instrument domains is 0.81, and all domain-total correlations are greater than
      0.4. All correlations between the final instrument and the construct validity
      instruments were statistically significant (P < .001), but not so high that they
      appeared to be measuring the same thing. Correlations between instruments
      measuring the same construct were higher than those measuring related but
      different constructs. Correlations between the final instrument and the CES-D
      scale, emotional exhaustion, and depersonalization subscales of the Maslach
      Burnout Inventory were negative. A test-retest reliability study on 42 physicians
      showed Pearson's correlation coefficients for individual domains were all greater
      than 0.7 and greater than 0.8 for the final instrument. This study has produced a
      valid and reliable instrument for measuring emergency physician job satisfaction,
      which is both internally consistent and stable.

PMID- 8285953
TI  - Use of transesophageal echocardiography in the detection and consequences of an
      intracardiac bullet.
AB  - A 17-year-old male sustained a gunshot injury to the chest. Transesophageal
      echocardiography showed the presence of a retained bullet in the pericardium and
      the absence of an intracardiac shunt, which provided important information for
      the treatment of the patient.

PMID- 8285954
TI  - Patterns of oxygen transport in trauma and their relationship to outcome.

PMID- 8285955
TI  - Observation unit impact on ED admission for asthma.
AB  - The hypothesis that the use of an observation unit (OU) in the emergency
      department (ED) results in monetary savings by lowering the hospital admission
      rate for asthma was studied in a retrospective comparative cohort at an urban
      university county hospital. All acute asthmatic patients seen in the ED during a
      22-month period were included. Preobservation patients were seen before the OU
      opened (n = 834); postobservation patients were treated afterward (n = 390).
      Postobservation patients in the experimental group meeting standard criteria were
      admitted to the OU. Fisher's exact test and the binomial distribution were used
      to analyze proportions of patients admitted. Median charges were compared with
      the Mann-Whitney test. The difference between groups in hospital admission rate
      was only 2.7% and was not significant (P = .25). However, 5.3% less patients were
      admitted directly to the hospital (P = .01), and 6.7% less patients were
      discharged directly from the ED (P = .005). The OU produced no demonstrable cost
      savings. The use of an OU for asthmatic patients results in lower initial
      discharge rates from the ED and does not reduce eventual hospital admission
      appreciably.

PMID- 8285956
TI  - Improving the quality of emergency medicine rotation/clerkship evaluations.
AB  - The process of evaluating the performance of medical students and/or residents
      during emergency medicine clinical rotations is constrained by several potential
      shortcomings. These constraints can limit the quality of the information provided
      to the student/resident, as well as that provided to the sponsoring institution.
      During the course of an academic year at United States Air Force Medical Center,
      Wright-Patterson, a number of medical students, interns, and residents rotate
      through the emergency department. The limitations identified in the process of
      evaluating these trainees include the (1) retrospective nature of the data
      provided in evaluations; (2) the lack of clear pre-established performance
      criteria; (3) the time constraints placed on preceptors; and (4) the incremental
      nature of the observations of performance during emergency medicine rotations.
      The evaluation tool developed to address these limitations is presented as a
      mechanism to help improve the ability of educators to evaluate and record
      performance during emergency medicine rotations.

PMID- 8285957
TI  - Israeli ED experience during the Gulf War.
AB  - The experience in an emergency department (ED) during the Gulf War in treating
      casualties referred to the ED soon after each missile attack is reported. Data
      were gathered within an 8-hour period of each nationwide alert on all patients
      who presented to the ED with injuries or complaints directly related to the
      missile attacks of the Tel Aviv area. One hundred three patients presented with
      symptoms directly related to the missile attacks. Of 103, 70 suffered from acute
      psychological reaction, 19 from false autoinjection of atropine, and nine from
      physical injuries from the explosion. Of the remainder, four had mild symptoms of
      smoke inhalation, and one had intercurrent myocardial infarction. The missile
      attacks resulted in a relatively small number of serious injuries. Most of the
      patients who presented to the ED soon after the missile attacks suffered from
      either anxiety reaction or false atropin injection.

PMID- 8285958
TI  - Chest pain evaluation in the ED: beyond triage.

PMID- 8285959
TI  - Albuterol protocol.

PMID- 8285960
TI  - Albuterol.

PMID- 8285961
TI  - Emergency cricothyrotomy.

PMID- 8285962
TI  - Physician business cards enhance patient satisfaction.

PMID- 8285963
TI  - Safer right subclavian vein puncture: the importance of pressing the needle with
      the left thumb.

PMID- 8285964
TI  - Toxicology screening and substance abuse consultations in acutely traumatized
      patients.

PMID- 8285965
TI  - Radiation exposure from cervical spine radiographs.
AB  - Radiation exposure to hospital personnel during 41 cervical spine radiographs of
      30 multiply injured patients was prospectively evaluated. A digital dosimeter was
      attached to the exposed torso of personnel applying upper extremity traction or
      managing the airway. Radiation exposure was measured during each radiograph. Any
      exposure of one or more milliroentgen was detectable. No radiograph resulted in a
      measurable radiation exposure. Multiple radiographs (up to five exposures) also
      did not register even the minimum recordable exposure, demonstrating that
      exposure is less than 1.0 mR per radiograph (P < .05). We conclude that hospital
      personnel, even those applying traction or managing the airway, are not at risk
      of significant radiation exposure at the time of cervical spine radiographs.

PMID- 8285966
TI  - One-year survival after prehospital cardiac arrest: the Utstein style applied to
      a rural-suburban system.
AB  - To evaluate the recently published Utstein algorithm (Ann Emerg Med 1991;20:861),
      the authors conducted a retrospective review of all advanced life support (ALS)
      trip sheets and hospital records of patients with prehospital cardiac arrests
      between January 1988 and December 1989. Telephone follow-up was used to determine
      1-year survival rates. Of 713 arrests in the 24-month study period, 601 were of
      presumed cardiac etiology. Approximately 599 of these charts were available for
      analysis. One hundred ninety-three (32.2%) of these had return of spontaneous
      circulation (ROSC), 36 (6.0%) survived to hospital discharge, and 24 were alive
      at 1-year follow-up (4.0% of total or 67% of survivors to discharge). The Utstein
      style was found to be a useful algorithmic format for reporting prehospital
      cardiac arrest data in a manner that should allow direct comparison between
      emergency medical service (EMS) systems. Existing prehospital record-keeping
      practices (trip sheets) are easily adapted to this style of data collection,
      although certain data for the template (eg, resuscitations not attempted and
      alive at 1-year) are more difficult to ascertain. Additionally, the authors
      report their own experience during a 2-year period, including data that suggest
      that the majority of patients with cardiac arrest who survive to hospital
      discharge are still alive at 1 year.

PMID- 8285967
TI  - Prehospital recognition of AMI using independent nurse/paramedic 12-lead ECG
      evaluation: impact on in-hospital times to thrombolysis in a rural community
      hospital.
AB  - Because the benefits from thrombolytic therapy in acute myocardial infarction
      (AMI) are time dependent, multiple strategies have been devised to speed therapy.
      This study sought to determine whether hospital-based nurse and paramedic
      advanced life support (ALS) providers could be trained to independently evaluate
      (sight read) a prehospital 12-lead electrocardiogram (ECG) for the presence of
      AMI as part of a protocol designed to speed in-hospital administration of
      thrombolytic agents. Providers were required to determine on the basis of a
      protocol (1) whether or not AMI was present, and (2) whether or not thrombolytic
      therapy was indicated. Providers then radioed their impression to the emergency
      department (ED) and initiated a protocol to prepare identified candidates for
      thrombolysis. The final decision to initiate thrombolytic therapy was made by the
      ED physician after patient arrival at the hospital. One hundred fifty-five
      patients with chest pain were studied. Twenty-one (13.5%) were ultimately proven
      in-hospital to have AMI. Providers were able to recognize AMI in 17 of 21. Four
      of 21 did not meet ECG criteria for AMI on the field ECG, but were categorized as
      having a high index of suspicion for AMI by providers. There were no false
      positive diagnoses. Fourteen patients (9%) received thrombolytic therapy. In
      hospital times to administration of thrombolytic therapy decreased to an average
      of 22 +/- 13.8 minutes in the studied group compared with a historical control
      group average of 51 +/- 50 minutes. It is concluded that hospital-based
      paramedics and nurses can successfully be taught to evaluate (ie, sight read) a
      prehospital ECG for the presence of AMI with accuracy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8285968
TI  - Lactic acidosis and acute ethanol intoxication.
AB  - Ethanol intoxication has been widely reported as a cause of lactic acidosis. To
      determine the frequency and severity of ethanol-induced lactic acidosis, patients
      who presented to an emergency department with a clinical diagnosis of acute
      ethanol intoxication and a serum ethanol concentration of at least 100 mg/dL were
      studied. Arterial blood was sampled for lactate and blood gas determinations. A
      total of 60 patients (mean age, 41 years) were studied. Twenty-two patients
      sustained minor trauma. Ethanol concentrations ranged from 100 to 667 mg/dL
      (mean, 287 mg/dL). Lactate concentrations were abnormal (> 2.4 mmol/L) in seven
      patients (11.7%). In all cases, blood lactate was less than 5 mmol/L. Of the
      patients with elevated lactate, other potential causes for lactic acidosis,
      including hypoxia, seizures, and hypoperfusion, were also present. Only one case
      with elevated blood lactate concentration had associated acidemia. Significant
      elevations of blood lactate are uncommon in acute ethanol intoxication. In
      patients with ethanol intoxication who are found to have lactic acidosis, other
      etiologies for the elevated lactate level should be considered.

PMID- 8285969
TI  - Resuscitation of canine hemorrhagic hypotension with large-volume isotonic
      crystalloid: impact on lung water, venous admixture, and systemic arterial oxygen
      saturation.
AB  - The objective of this study was to test the hypothesis that after hemorrhagic
      hypotension, reinfusion of the shed blood with threefold that volume of lactated
      Ringer's (LR) solution will significantly increase lung water and venous
      admixture and hence decrease systemic arterial oxygen saturation. A prospective,
      randomized, fixed-volume hemorrhage laboratory study was performed at the
      Oklahoma University Health Sciences Center on 18 anesthetized mongrel dogs. After
      40 mL/kg of blood were withdrawn through a femoral artery catheter, the dogs were
      randomized either to the control group (n = 9) that received a reinfusion of the
      shed blood, or to the LR treatment group (n = 9) that received an intravenous
      mixture of the shed blood with 120 mL/kg of LR. After fluid resuscitation,
      pulmonary artery occlusion pressure (PAOP) and cardiac output (CO) were
      significantly increased in the LR group compared with control animals (PAOP, 18.7
      +/- 1.1 vs 13.4 +/- 2.9 mm Hg; CO, 8.14 +/- 1.08 vs 4.59 +/- 0.47 L/min; P < .05
      each). However, lung water, venous admixture, and systemic arterial PO2 were
      similar between groups. In this fixed-volume hemorrhage model, hemodiluting the
      reinfused shed blood with threefold the volume of LR did not significantly
      influence lung water, venous admixture, or systemic arterial oxygen saturation.

PMID- 8285970
TI  - Bupropion overdose: a 3-year multi-center retrospective analysis.
AB  - Bupropion (Wellbutrin; Burroughs Welcome Co, Research Triangle Park, NC) is a
      unique monocyclic antidepressant about which there is limited overdose
      information. A retrospective analysis of all bupropion ingestions reported to
      five regional poison control centers from 1989 through 1991 was conducted. There
      were 58 cases of bupropion ingestion and nine cases of combined bupropion and
      benzodiazepine ingestion. Sinus tachycardia was the only toxic cardiovascular
      effect noted, except for one case of hypotension in the bupropioin and
      benzodiazepine group. Neurological toxicity was commonly encountered and included
      lethargy, tremors, and seizures. Both benzodiazepines and phenytoin were
      efficacious in controlling seizures. Five cases of pure bupropion overdose had
      electrolytes reported. Serum potassium ranged from 2.6 to 4.2 mEq/L (mean, 3.3
      mEq/L). In overdose, bupropion seems to lack major cardiovascular toxicity;
      however, it does manifest significant neurological toxicity.

PMID- 8285971
TI  - Adverse lighting condition effects on the assessment of capillary refill.
AB  - In 1989, Champion et al recommended revising the Trauma Score to exclude
      capillary refill because it is "difficult to assess at night. . . ." However, a
      literature search produced no studies evaluating the effect of lighting
      conditions on the assessment of capillary refill. This study was undertaken to
      determine if any such effect exists. Three hundred nine participants at an
      emergency medical services (EMS) seminar were asked to assess each others'
      capillary refill in both light and dark environments. The participants were
      nurses, emergency medical technicians (EMTs), and paramedics who had been
      instructed in the assessment of capillary refill. In daylight conditions (partly
      cloudy day, lux meter = 15 to 16), capillary refill was reported as normal in
      94.2% of the participants, delayed in 1.9% of the participants, and undetected in
      3.9% of the participants. In dark conditions (moonlight or street lamp, lux meter
      = 4 to 6), capillary refill was reported as normal in 31.7% of the participants,
      delayed in 1.6% of the participants, and undetected in 66.7% of the participants.
      chi 2 analysis demonstrated a statistically significant difference between
      capillary refill assessment in light versus dark environments (P < .001).

PMID- 8285972
TI  - Clinical application of infrared thermography in the diagnosis of appendicitis.
AB  - To determine the clinical usefulness of infrared skin temperatures in diagnosing
      appendicitis, the authors conducted a prospective study of 86 adult and pediatric
      emergency department (ED) patients presenting during a 4-month study period with
      acute right lower abdominal pain. Skin temperature readings (FirstTemp digital
      thermometer, Intelligent Medical Systems, Inc, Carlsbad, CA) were taken from the
      right lower abdominal quadrant and a corresponding position on the left. An
      unpaired t test was used to determine if there was a significant difference
      between the right and left lower quadrants in patients with appendicitis.
      Discharged patients were followed up by telephone to determine any subsequent
      morbidity. A total of 23 patients had appendicitis confirmed by surgery; 63
      subjects had other medical diagnoses. There was no significant skin temperature
      differential between the lower abdominal quadrants in either patient group (0.0
      degree C vs 0.1 degree C; P > .5). Three patients had a skin temperature on the
      right that was at least 1 degrees C warmer than on the left; none of these
      patients had appendicitis. The results suggest that infrared thermography is not
      a sensitive diagnostic test for acute appendicitis in the ED population.

PMID- 8285973
TI  - Clinical characteristics of acute uvulitis.
AB  - Previous literature has identified uvulitis as a condition with serious
      implications. This report details a series of 15 patients with uvulitis whose
      clinical features were remarkable for a relatively benign course. This is the
      largest series of patients with uvulitis in the literature. The predominant
      symptoms were related to sore throat and pain or difficulty on swallowing. No
      patient had significant airway or infectious complications attributable to the
      uvulitis. The only patient admitted to the hospital required management of an
      associated peritonsillar abscess. Of the 14 patients discharged, 13 (93%) were
      followed-up and none required further care. Seven (50%) of the discharged
      patients received symptomatic treatment only, whereas the others were treated
      with medications including antibiotics, corticosteroids, diphenhydramine, and B
      agonists. Further research into the etiology and management of uvulitis is
      warranted.

PMID- 8285974
TI  - Delayed appendicitis from an ingested foreign body.
AB  - An unusual case of acute appendicitis induced by a metal drill bit that was
      ingested by a 27-year-old man 3 years before presentation is reported. This
      foreign body lodged in the patient's appendix and developed a fecalith coating.
      When this fecalith coating enlarged enough to obstruct the appendiceal lumen, the
      patient presented with classic acute appendicitis. Foreign body-induced
      appendicitis is reviewed.

PMID- 8285975
TI  - Acute toxicity from baking soda ingestion.
AB  - Sodium bicarbonate is an extremely well-known agent that historically has been
      used for a variety of medical conditions. Despite the widespread use of oral
      bicarbonate, little documented toxicity has occurred, and the emergency medicine
      literature contains no reports of toxicity caused by the ingestion of baking
      soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic
      alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia,
      hypokalemia, hypochloremia, intravascular volume depletion, and urinary
      alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may
      result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of
      calcium and phosphorus metabolism. The case of a patient with three hospital
      admissions in 4 months, all the result of excessive oral intake of bicarbonate
      for symptomatic relief of dyspepsia is reported. Evaluation and treatment of
      patients with acute bicarbonate ingestion is discussed.

PMID- 8285976
TI  - Infection control for health care workers caring for critically injured patients:
      a national survey.
AB  - Prevention of transmission of bloodborne pathogens to health care workers (HCWs)
      involved in resuscitation of critically injured patients presents special
      challenges. As a step toward creation of a standard, a telephone survey of the
      infection control practices in this setting of the 100 busiest EDs in the United
      States (US) was performed. Departmental staff who were knowledgeable about ED
      infection prevention protocols were questioned about general policy, barrier
      protection measures, sharps management, and educational programs directed to
      HCWs. Surveys were completed for 82 EDs. Of these, 56 (68%) either function as
      primary trauma care facilities for the local community, or are designated level 1
      trauma centers by the American College of Surgeons. Specific infection control
      protocols for trauma resuscitation had been printed and posted by 18 EDs (22%),
      with the remaining 64 (78%) using the same universal precautions for care of the
      severely injured as for other patients. A specific policy relating to invasive
      procedures had been promulgated by 66 EDs (80%). Barrier protection was used by
      protocol or by custom for care of all critically injured patients by 43 EDs
      (52%). Impermeable gowns with sleeves were available in 63 EDs (77%). Eye or face
      protection included face shields by 74 EDs (90%), face masks by 76 EDs (93%), and
      goggles by 72 EDs (88%). Only 59 EDs (72%) reported that sharp containers were
      always within arm's reach of HCWs with material to discard. Specially adapted
      equipment included self-sheathing intravenous catheters (21, 26%) and
      needle/syringe combinations (16, 20%). Considerable variation exists in infection
      control practices in busy US EDs during resuscitation of critically injured
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285977
TI  - Hypokalemia after pediatric albuterol overdose: a case series.
AB  - Sympathomimetic use results in a triad of hypokalemia, hyperglycemia, and
      elevated white blood cell count. Transient hypokalemia results from activation of
      the Na+/K+ pump and transport of potassium intracellularly. Increased serum
      glucose and insulin may also contribute to the intracellular shift of potassium
      after sympathomimetic use. Four cases of accidental pediatric albuterol ingestion
      with significant hypokalemia are reported. Four children between 1 and 6 years of
      age presented to the emergency department within 5 hours of ingesting 3.0, 1.1,
      3.7, and 1.7 mg/kg albuterol, respectively. All four presented alert and oriented
      in no apparent distress. The most common findings were vomiting, sinus
      tachycardia, and hypokalemia (2.3, 2.5, 2.8, and 2.5 mmol/L, respectively). Each
      child received a single dose of activated charcoal and intravenous potassium
      replacement. All patients recovered uneventfully within 12 to 24 hours with
      supportive care only. These cases demonstrated that significant depressions in
      serum potassium can occur after pediatric albuterol overdose. Although transient,
      the dose-response relationship and duration of effect is unknown. Although
      significant hypokalemia can occur after ingestion of oral sympathomimetics,
      replacement should be managed on an individual basis until further studies are
      completed.

PMID- 8285978
TI  - Severe low back pain secondary to acute interstitial nephritis following
      administration of ranitidine.
AB  - Acute interstitial nephritis is a disease characterized by renal inflammation and
      is thought to be secondary to a hypersensitivity reaction. Although the causes of
      acute interstitial nephritis are numerous, adverse reactions to many common
      drugs, particularly antibiotics and nonsteroidal anti-inflammatory agents, are
      important etiological factors. Acute interstitial nephritis has many clinical
      manifestations, most notably fever and rash. Flank pain is an uncommon
      presentation. A case of acute, severe, low-back pain and rash in a healthy woman
      found to be secondary to acute interstitial nephritis is reported. The etiology
      of acute interstitial nephritis in this patient's case is suspected to be
      ranitidine (Zantac; Glaxo Pharmaceuticals, Research Triangle Park, NC), which has
      not been previously associated with this syndrome.

PMID- 8285979
TI  - ST-segment instability preceding simultaneous cardiac arrest and AMI in a patient
      undergoing continuous 12-lead ECG monitoring.
AB  - Little data exist concerning the actual onset time (time zero) in sudden death
      (SD) and acute myocardial infarction (AMI). Most studies have focused on
      describing the warning arrhythmias that occur before SD and AMI and have relied
      on retrospective analyses of fortuitous data obtained from patients who
      experience these adverse outcomes while undergoing routine ambulatory holter
      monitoring. Because of the limitations of holter monitoring, little information
      is known concerning the actual incidence of ST-segment changes preceding SD and
      AMI. The first case of simultaneous onset of silent SD and AMI occurring in a
      patient undergoing continuous 12-lead electrocardiograph (ECG) monitoring during
      his initial emergency department evaluation is reported. Analyses of the serial
      12-lead electrocardiographs showed extensive transient silent ST-segment
      elevations and depressions preceding cardiac arrest and AMI and provided insight
      in the pathogenesis of SD and AMI. Continuous 12-lead ECG monitoring can identify
      patients at high risk for SD and AMI and allow physicians to intervene before the
      development of life-threatening conditions.

PMID- 8285980
TI  - Ceramic lead glaze ingestions in nursing home residents with dementia.
AB  - Three cases of acute lead ceramic glaze ingestions that occurred in elderly
      patients during art therapy classes in nursing homes are reported. Initial blood
      lead levels were 109 micrograms/dL (5.23 mumol/L), 259 micrograms/dL (10.43
      mumol/L), and 85 micrograms/dL (4.08 mumol/L), respectively, and all patients
      underwent chelation therapy. Two individuals tolerated therapy well and showed no
      discernable changes from baseline state. One patient with a lead encephalopathy
      died and is, to the best of our knowledge, the first report of a death directly
      related to a ceramic lead glaze ingestion. Ceramic lead glaze ingestions among
      institutionalized patients may be more common than generally appreciated and
      occasionally are associated with significant morbidity or, rarely, mortality.
      Simple preventive measures could eliminate the majority of such occurrences.

PMID- 8285981
TI  - Postpartum ovarian vein thrombosis.
AB  - Ovarian vein thrombosis is a rare occurrence in the postpartum period. Two cases
      of postpartum ovarian vein thrombosis are presented. The differential diagnosis
      is extensive because many diseases can present with similar symptoms. Early
      diagnosis is essential for appropriate treatment and prevention of the potential
      sequelae that can occur. Computerized tomography with contrast is the optimal
      imaging modality for the diagnosis.

PMID- 8285982
TI  - Atypical migraine presenting with meningeal signs.
AB  - A case of atypical or complicated migraine is presented with signs and symptoms
      of meningeal irritation, projectile emesis NS obtundation, and unresponsiveness.
      The patient is a 19-year-old diabetic on insulin who had a mild episode of upper
      respiratory tract symptoms with severe headache and was found unresponsive and
      brought to the emergency department. After a work-up for meningitis was negative
      (as well as computerized tomography and magnetic resonance imaging) he recovered
      totally in 3 days with no residual signs or symptoms and was discharged from the
      hospital.

PMID- 8285983
TI  - Pseudofractures of the mandible secondary to motion artifact.
AB  - The case of a patient with a false-positive fracture on the panoramic view of the
      mandible is presented. The patient motion produced a spurious image that
      perfectly mimicked a fracture without any evidence of motion. To better assess
      motion artifact, panoramic views of a "phantom" human skull were developed with
      movement during the exposure. These radiographs were analyzed with the assistance
      of a radiologist, and diagnostic features of motion artifact are discussed. Some
      radiographs were created by movement that mimicked fractures without the telltale
      signs of motion artifact. These "motion pseudofractures" are diagnosed clinically
      if the examiner knows that motion can mimic fractures, and all x-ray findings are
      carefully correlated with clinical findings. Diagnosis of a motion pseudofracture
      will avoid the additional expense and time of a specialty consultation.

PMID- 8285984
TI  - The incidence of spontaneous subarachnoid hemorrhage with change in barometric
      pressure.
AB  - The authors' observation of an apparent increased incidence of patients
      presenting with spontaneous subarachnoid hemorrhage (SAH) during stormy weather
      prompted them to retrospectively review admissions data during an 18-month period
      to look for an association between SAH and changes in barometric pressure (BMP).
      Of the 39,049 cases examined, 76 had confirmed SAH. Continuous graphs of BMP were
      used to categorize days as being "flat" days (change in BMP < or = 0.15; dpHg) or
      "change" days (change in BMP > 0.15; dpHg). Days on which patients presented with
      SAH were significantly correlated with change days (P < .004). There was
      significantly more SAH during the winter months (October to March), than during
      the remaining summer months (P < .02). The correlation of SAH with change in BMP
      did not hold if these summer months were examined alone. The risk ratio of having
      an SAH on an inclement day during the winter months was 1.99 (95% confidence
      interval, 1.11 to 3.60). The reason for this association is not clear at this
      time.

PMID- 8285985
TI  - Traumatic train injuries.
AB  - Train accidents involving motor vehicles and pedestrians can be devastating.
      Approximately 1,234 fatalities were recorded in the United States in 1989. The
      literature from the United States is sparse, prompting a 7-year review of 23
      consecutive train accident victims. Twenty (87%) were male, with an average age
      of 30.6 years. Sixteen (70%) were intoxicated at the time of the accident, and
      the average Injury Severity Score was 21.4. There was a total of eight traumatic
      amputations occurring in the 11 (48%) patients involved as pedestrians. Two of
      these were railroad workers, and nine were trespassers. Fourteen (61%) accidents
      occurred between the hours of 2300 and 0700. Three (14%) patients died. Although
      alcohol use occurred in 16 (70%), there was no significance between alcohol use
      and amputation. Thus, non-railroad employed pedestrians, because of a lack of
      protection, are more prone to traumatic amputations, primarily of the lower
      extremities, than those involved in motor vehicle accidents.

PMID- 8285986
TI  - Rotaviral gastrointestinal infection causing afebrile seizures in infancy and
      childhood.

PMID- 8285987
TI  - Topical lidocaine and proparacaine abuse.

PMID- 8285989
TI  - Turnover of deans of medicine during the last five decades.
AB  - This report uses published information on the tenures of the 862 U.S. medical
      school deans who served from 1940-41 through 1990-91 to ascertain whether the
      turnover of deans has increased historically. The data confirm the wide-spread
      impression that there has been increasing instability of medical school
      leadership in recent decades. The proportion of deans who survive to a specific
      tenure in office has diminished, and the proportion of schools with new deans has
      increased, although with marked yearly fluctuations. Furthermore, the frequency
      of deans' turnover has not been evenly distributed among medical schools. Some
      schools have had large numbers of short-tenured deans, while other schools have
      had only a few deans over the five decades studied. The authors speculate that
      the rise in the turnover of deans may be related to the criteria used for their
      selection and/or because American academic medical centers have grown in size and
      are increasing in organizational complexity. The authors urge that future
      research that explores the causes of recent deans' turnover should incorporate
      modern management and statistical techniques and consider organizational
      variables as well as the personal and professional characteristics of deans.

PMID- 8285988
TI  - Diagnosis, complications, and treatment of dentoskeletal malocclusion.
AB  - The frequency of correctable malocclusion makes it imperative that the condition
      be diagnosed and referred for appropriate treatment. A complete dentofacial
      examination, which assesses facial symmetry and the dentition in the transverse,
      sagittal, and centric relations, is appropriate. Early diagnosis is imperative
      because malocclusion leads to long-term complications such as temporomandibular
      joint (TMJ) dysfunctions, perodontal disease, obstructive sleep apnea,
      psychological disorders, and articulation errors. A combination of orthodontic
      treatment and orthognathic surgery will correct the dentoskeletal malocclusion
      and prevent any long-term complications. The purpose of this case report is to
      describe a patient with severe dentoskeletal malocclusion who benefitted from
      appropriate orthodontic treatment and orthognathic surgery.

PMID- 8285990
TI  - A structured clinical feedback exercise as a learning-to-teach practicum for
      medical residents.

PMID- 8285992
TI  - Plagiarism and biomedical publishing.

PMID- 8285991
TI  - An Internet primer: resources and responsibilities.
AB  - The ease with which individuals can access the Internet and with which
      institutions can make information available on the Internet explains the
      exponential growth of this national resource. Once one accomplishes the difficult
      task of installing network services and establishing an ongoing mechanism for
      their support, it is relatively simple to use software systems such as those
      described in this article to gainfully traverse the Internet for a wide range of
      professional activities. But, as we have discussed, every step of the process,
      from simple naming conventions to organizations and ongoing maintenance of
      network-based information services, should proceed only after careful
      consideration of a network growing hourly in complexity. Despite the power of the
      technology available on one's desktop, one can often be frustrated by the small
      decisions: what is my colleague's email address? How can I most effectively find
      relevant information on home health care software? How should I organize a gopher
      server? When is WAIS preferable to Gopher or W3? Who will help me learn more? The
      process comes full circle back to academic medical institutions. The usefulness
      of the Internet hinges upon the policies these institutions create to aid the
      organization and dissemination of medical information, and in the means they use
      to make their constituents aware of the pitfalls and potentials of various
      technologies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8285993
TI  - The illegal use of NBME examination materials.

PMID- 8285994
TI  - GPEP report recommends traditional and nontraditional approaches.

PMID- 8285996
TI  - CGEA's fellowship in medical education research. Central Group on Educational
      Affairs.

PMID- 8285995
TI  - LCME accreditation standards for management of the medical school curriculum: a
      clarification. Liaison Committee on Medical Education.

PMID- 8285997
TI  - Retired physicians in undergraduate medical education.

PMID- 8285998
TI  - Creating a code of conduct for and by medical students.

PMID- 8285999
TI  - Educating medical students: lessons from research in continuing education.
AB  - Creating a true continuum of medical education from admission to medical school
      throughout a lifetime of professional learning is easier said than done. To do
      so, the various components on the continuum must be explored to determine where
      appropriate links might be made. The author considers selected concepts and
      evidence from the theory and practice underlying continuing medical education
      (CME) and continuing professional education (CPE) insofar as CME and CPE can
      inform undergraduate medical curricula, including its current innovations. Five
      conceptual and empirical approaches from CME and CPE are discussed in detail:
      social learning theory, how physicians learn and change, competence in business
      and the professions, how professionals learn in practice, and lifelong self
      directed learning. Then the author describes the implications of these approaches
      for the ongoing development of undergraduate medical education. (1) The entire
      learning environment, and not merely discrete aspects such as curriculum content,
      must be examined and fully utilized to benefit learning. (2) The importance of
      the contexts in which learning occurs must be emphasized in several ways. (3)
      Learning should be centered around clinical problems. (4) The many benefits of
      small-group learning and other ways of learning from colleagues should be
      emphasized. (5) The undergraduate curriculum should emphasize the development of
      students' feelings of self-efficacy to ensure that students become physicians who
      are confident about their abilities. (6) CME research and CPE research reinforce
      the efforts in undergraduate medical education to emphasize the early development
      of students' process skills as well as content mastery.

PMID- 8286000
TI  - Orientation of medical residents to the psychosocial aspects of primary care:
      influence of training program.
AB  - PURPOSE: To describe the attitudes of residents in general medicine to the
      psychosocial dimensions of primary care and to evaluate the influences of
      selected variables. METHOD: A cross-sectional analysis-of-variance design (two
      training programs involving residents in all three residency years) was used in
      the analysis of 21 psychosocial attitude items from a survey questionnaire
      completed by general medicine residents. In 1991-92, 77 general medicine
      residents in ambulatory care group practices associated with the Massachusetts
      General Hospital were surveyed. Eighteen of the residents were in a primary care
      program (PCP), and 59 were in a traditional medicine program (TMP). RESULTS: The
      overall response rate was 82% (63 of 77 residents), with slightly lower rates for
      four items. The residents' attitudes to the psychosocial role of the primary care
      physician were positive but with reservations: 55 (87%) endorsed asking
      psychosocial questions, while only 28 (44%) indicated that most internists felt
      competent to diagnose and treat. Most residents did not feel defensive about
      enacting the role (neither uncomfortable asking questions in ambulatory care
      settings, 58, 92%; nor nosey, 56, 89%; nor personally interfering, 47, 76%).
      Fifty-two residents (83%) perceived patients to be receptive to psychosocial
      questions, yet 31 (49%) indicated that patients were resistant to psychosocial
      attributions, and 48 (76%) indicated that patients need to be prompted to talk
      about life problems. The clearest and strongest influence on attitudes was
      setting: ambulatory care over inpatient (p < .0001). Overall, the responses of
      the residents from the PCP and TMP were more similar than different. CONCLUSION:
      The residents accepted the psychosocial role of the primary care physician, found
      it most appropriate in ambulatory care settings, felt ambivalent about their
      ability to carry it out, and assigned it a secondary priority in patient care. To
      interest residents in primary care, more training should be based in ambulatory
      care settings and more emphasis should be placed on improving residents'
      competency in psychosocial skills.

PMID- 8286001
TI  - Undergraduate clinical education in internal medicine at Canadian medical
      schools.
AB  - PURPOSE: To document the characteristics of the clinical education in internal
      medicine of undergraduate medical students at Canadian medical schools. METHOD: A
      five-part questionnaire was sent in 1991-92 to the individuals responsible for
      supervising the internal medicine clerkships at all 16 Canadian medical schools.
      The questions were related to (1) tutors, hospitals, and inpatient clinical
      experiences of internal medicine clerks; (2) ambulatory care experiences; (3)
      evaluation methods; (4) "junior clerkships" (i.e., clinical courses that precede
      the clerkships); and (5) supervisors' opinions about changes needed to improve
      the clerkships. RESULTS: Responses were received from all schools. There was
      surprising uniformity in clinical education across Canada. Clinical education
      methods have changed very little over the past decade. In the opinion of the
      clerkship supervisors, there were too few committed clinical tutors, little
      evidence of use of newer evaluation methods, and inadequate ambulatory care
      instruction. CONCLUSION: The study results suggest that the clinical education in
      internal medicine of undergraduate medical students has changed little despite
      numerous calls for reform.

PMID- 8286002
TI  - A model to determine the influence of medical school on students' career choices:
      psychiatry, a case study.
AB  - BACKGROUND: A major concern of medical educators is to understand better how the
      experience of medical school influences students' career choices. This concern is
      of particular relevance for specialties experiencing or anticipating serious
      shortages (e.g., psychiatry, generalist specialties, general surgery). METHOD: To
      construct a case study of a model to determine the influence of medical school on
      students' selections of specialty, Association of American Medical Colleges
      (AAMC) databases were used to examine students' interests in one specialty
      (psychiatry) at two time periods: (1) at or before matriculation and (2) in the
      first year of residency. Data were examined for all graduates of all U.S. medical
      schools from 1991 and 1992. In addition to examining data for each school
      individually, comparisons were made of schools by region and by institutional
      control (public or private). RESULTS: Increased interest in psychiatry was found
      in seven of eight regions across the country. The greatest increases were found
      among graduates of public and private medical schools in the southeast: both
      types of schools increased the interest in psychiatry among their graduates by
      250%, compared with the national average of 170%. A decrease in interest in
      careers in psychiatry was found among graduates of private medical schools in the
      northeast. CONCLUSION: The findings point to one way of understanding better the
      influence of a medical school on its students' career choices. By using this
      model, each specialty may be able to develop studies to examine the complex
      interactions between students and specific medical schools.

PMID- 8286003
TI  - Students' time allocation in a required third-year ambulatory care clerkship.
AB  - PURPOSE: To assess time use by students during clinic sessions of an ambulatory
      care clerkship. METHOD: All 207 third-year students at the Medical College of
      Wisconsin during 1991-92 were asked to report their time use in eight categories
      during two clinic sessions of the three-week clinical component of the required
      clerkship in ambulatory care medicine. Other variables assessed were site of
      clinical rotation, first versus third week of rotation, and time of year of
      rotation. The statistical methods used were t-tests and one-way analysis of
      variance. RESULTS: Of the 207 students, 192 (93%) completed time-allocation
      reports for the first and third weeks of their rotations. The average time spent
      per clinic session was four hours. Compared with the students at faculty practice
      sites, the students at private practice sites spent significantly more time
      observing and working with preceptors as they saw patients and significantly less
      time doing solo clinical work (reviewing and writing in charts). During the
      course of each rotation, the students increased the time they saw patients by
      themselves and decreased the time they observed preceptors. As the year
      progressed, later cohorts of students spent less time observing preceptors and
      more time working by themselves. CONCLUSION: Both within and across rotations,
      the students eventually spent less time observing and more time working
      independently. However, the results suggest that preceptors in private practice
      may not allow students as much autonomy as do faculty preceptors. Further
      research is needed to determine (1) whether the differences between types of
      preceptors result in meaningful differences in the quality of education and (2)
      which activities or mixes of activities contribute most to students' education.

PMID- 8286004
TI  - Facilitating faculty development and research through critical review of grant
      proposals and articles.
AB  - BACKGROUND: In 1983 the Department of Pediatrics at the University of Texas
      Medical Branch at Galveston established a faculty development program to address
      faculty needs for continuing education and improved resources for research. At
      first a part-time coordinator was hired; then, in 1985, a full-time, faculty
      level science communicator provided help with strategic planning of projects and
      intensive review of grant proposals and journal articles. Faculty participation
      in the program was voluntary. METHOD: Pre- and post-intervention data for 1983
      1992 included numbers of faculty using the program, faculty evaluations of the
      program, grant dollars awarded, counts of grant submissions and awards, and
      numbers of published articles. RESULTS: The review services were used heavily for
      grant proposals (75% of the department's proposals), but were used lightly for
      research articles (18% of publications). Grant funding quadrupled from 1983 to
      1988; although funding peaked in 1988, it thereafter remained at three to four
      times the 1983 level. In contrast, the mean number of publications per faculty
      per year dropped between 1983 and 1990. CONCLUSION: The program provided valuable
      assistance to the faculty in writing grant proposals, and it helped to generate
      critically needed resources. However, the program's failure to increase the
      publication productivity of the faculty suggests that despite financial
      pressures, similar programs should use their influence and resources to promote a
      balance between scholarly publication and grant acquisition.

PMID- 8286006
TI  - The depiction of medical education in medical school catalogs.
AB  - BACKGROUND: Medical educators bear responsibility for the informational materials
      that their institutions use to communicate with potential applicants. These
      documents, because they are often the first official correspondence that
      prospective students receive, may be influential in shaping students'
      expectations. METHOD: In March 1990 all North American medical schools that
      awarded MD or DO degrees were requested to send their catalogs and courses of
      study to the authors. In response came 175 documents, with nearly all the schools
      represented at least once. The photographs and other visual images in these
      documents were then analyzed from the perspective of a hypothetical applicant who
      perused what his or her initial request for information had produced. RESULTS:
      Nearly 3,400 images were analyzed and categorized according to content and
      stylistic approach. Two basic stylistic approaches were found: stylized and
      documentary. Few documents used exclusively one or the other approach, as the
      approaches represent poles along a continuum. The stylized approach portrays
      medical education as a product to be sold, whereas the documentary approach
      candidly tells the story of medical education. CONCLUSION: The authors conclude
      that the documentary approach is a more morally responsible way for schools to
      communicate with individuals who are in the beginning stages of building their
      mental images of medical education and medical care.

PMID- 8286005
TI  - Pilot study of the use of the ECFMG clinical competence assessment to provide
      profiles of clinical competencies of graduates of foreign medical schools for
      residency directors. Educational Commission for Foreign Medical Graduates.
AB  - PURPOSE: To conduct the first of a series of pilot projects of the clinical
      competence assessment (CCA) of the Educational Commission for Foreign Medical
      Graduates (ECFMG) in order to provide profiles of clinical competencies of
      graduates of foreign medical schools for residency directors in the United States
      and for governments and institutions in other countries. METHOD AND RESULTS: In
      September 1992 the first pilot project of the ECFMG CCA was conducted for a
      program director who wanted to evaluate ten first-year residents in a midwestern
      U.S. program. The CCA consists of integrated clinical encounters with ten
      standardized patients, 60 laser videodisc pictorials, and analysis of test items
      of previously completed ECFMG certification examinations. Profiles of the
      following clinical competencies were provided to the program director: data
      gathering (history and physical examination), interviewing and interpersonal
      skills, diagnosis and management skills, interpretation of diagnostic and
      laboratory procedures, written communication of information to the health care
      team, and spoken-English proficiency. The profiles were provided as individual
      scores compared with mean scores of a reference group of 525 first-year residents
      who took the CCA at four U.S. assessment centers, and as percentile scores with a
      range of one standard error of measurement. CONCLUSION: The individual
      performance data in this first pilot project were valuable to the program
      director, who used them to supplement scores on a written examination during the
      first residency year. The pilot project has shown the ECFMG CCA to be a useful
      tool for program directors to evaluate applicants and residents who are graduates
      of foreign medical schools.

PMID- 8286007
TI  - Medical school financing 1991-1992: comparing seven different types of schools.
AB  - Medical schools are often thought of as relatively homogeneous entities with
      similar financial and structural characteristics. In fact, they are of several
      types. For this report, the authors group the 126 accredited U.S. medical schools
      that share at least one key characteristic (e.g., being community-based) into
      seven groups, provide an analysis of the differences in revenue patterns for the
      groups, examine intragroup differences, and present detailed information about
      the student financial aid that all schools provide. The data used in this
      analysis were derived from the schools' responses to the Part 1A and the Part 1B
      questionnaires of the Liaison Committee on Medical Education for the academic
      year 1991-92. The results of the analysis indicate that there were substantial
      differences in the financial structures both within and between the groups
      studied. The differences suggest that generalizations regarding how medical
      schools will be affected by impending changes in health care reform are likely to
      be tenuous at best.

PMID- 8286008
TI  - Foundations that support medical education and health care: their missions,
      accomplishments, and unique role.
AB  - The author provides a detailed overview of the missions, accomplishments, current
      strategies, and unique institutional role of those U.S. private foundations that
      have a significant focus on health, especially those that emphasize the support
      of medical education. The major foundations of this kind are identified, their
      contributions during this century are described, and their current finding
      strategies and directions are listed. The author indicates the history of
      foundation giving during this century, discusses in detail the characteristics of
      five major foundations, indicates their influence in the medical education and
      public health arenas in the United States and around the world, and provides two
      tables with thumbnail sketches of 31 foundations working in these arenas. She
      concludes that foundations have offered and continue to offer to government,
      medical schools, and other health-promoting institutions an array of innovative,
      less traditional options and the results of pilot programs using these options.
      In this way, foundations provide challenges and guidance to these institutions to
      stretch toward better ways of fulfilling their missions. Clearly, foundations
      cannot fund the cost of reforming medical education and health care for the
      twenty-first century, but they have a crucial role in leading the way to such
      reform.

PMID- 8286009
TI  - Synthesis and evaluation of 4-amino-substituted 7-methoxy (and 7-hydroxy)- 11
      methyl (and 5,11-dimethyl)-10H-pyrido [2,3-b] carbazoles and 4-amino- substituted
      11-methyl (and 5,11-dimethyl)-10H-pyrido[3',4':4,5] pyrrolo [3,2-g] quinolines,
      two new series related to antitumor ellipticine derivatives.
AB  - 2-Acetyl-4-chloro-3-lithiopyridine ethylene glycol ketal (6b) was reacted with 3
      formyl-5-methoxy-1-methyl-indole (9) and 3-formyl-1-methyl-1H-pyrrolo [3,2-c]
      pyridine (12), giving the corresponding expected alcohols. Reduction of these
      intermediates with triethylsilane trifluoroacetic acid and subsequent
      cyclodehydration then led to 4-chloro-7-methoxy-10,11-dimethyl-10H-pyrido [2,3-b]
      carbazole (8a) and the corresponding 7-aza-analog (8b). The synthesis of 4-chloro
      11-methyl (and 5,11-dimethyl)-10-unsubstituted derivatives of these two series
      was performed through an independent pathway, involving condensation of
      conveniently substituted 2-amino carbazoles (17) and 7-amino-5H-pyrido [4,3-b]
      indoles (18) with 5-(ethoxymethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione, thermal
      cyclization of the resulting compounds with concomitant decarboxylation to the
      corresponding tetracyclic fused-4-quinolone systems and final chlorination with
      phosphorus oxychloride. Nucleophilic substitution of various 4-chloro derivatives
      was then easily performed in an excess of the required dialkylamino alkylamines
      at reflux and 4-amino substituted-7-hydroxy-10H- pyrido [2,3-b] carbazoles (25d
      e) were obtained from 7-methoxy precursors (25a-b), by demethylation with boron
      tribromide in methylene chloride at -65 degrees C or with boiling 47% hydrobromic
      acid. Cytotoxicity determination of all new aminosubstituted derivatives and in
      vivo antitumor evaluation of the most active compounds clearly show that these
      two series of ellipticine analogs closely related to highly active products are
      devoid of antitumor properties in two experimental models shown to be sensitive
      to ellipticines. The place of the pyridinic nitrogen atom in these series has
      thus been demonstrated to play a crucial role in antitumor activity.

PMID- 8286010
TI  - Inhibitory effects of cholera toxin on in vitro growth of human lung cancer cell
      lines.
AB  - Cholera toxin (CT) inhibited the growth of three out of 10 small cell lung cancer
      (SCLC) cell lines and two out of seven non-small cell lung cancer (NSCLC) cell
      lines when tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
      (MTT) assay. These CT-sensitive as well as CT-resistant cell lines bound well to
      the non-toxic CT-B subunit-fluorescein isothiocyanate conjugate (FITC-CTB) when
      assayed by flow cytometry. Using the reaction of horseradish peroxidase
      conjugated CT-B (HRP-CTB) on thin-layer chromatography (TLC), we analyzed
      gangliosides extracted from SCLC cell lines, CT-resistant SBC-1, minimally CT
      sensitive SBC-3 and CT-sensitive SBC-5. HRP-CTB was found to react not only with
      GM1, but also with Fuc-GM1, GD1b and other gangliosides on TLC. Although CT
      resistant SBC-1 cells bound well to FITC-CTB, the binding of gangliosides
      extracted from SBC-1 cells to HRP-CTB was markedly decreased when compared to
      those from CT-sensitive SBC-5 cells. The CT resistance of the minimally CT
      sensitive SBC-3 cell lines, which binds weakly FITC-CTB and HRP-CTB, was
      partially reversed by exogenous GM1 pretreatment. These observations suggest that
      the amount of gangliosides, such as GM1, Fuc-GM1 and GD1b, on the cells, rather
      than the CT-binding ability to the cells, plays a major role in cytotoxicity by
      CT.

PMID- 8286011
TI  - Synthesis and biological evaluation of phenanthrene-derived carboxamides as
      cytotoxic agents.
AB  - A series of phenanthrene-based tricyclic carboxamides has been synthesized as
      angular analogues of the clinical acridine carboxamide DACA, and their DNA
      binding, in vitro cytotoxicities and in vivo antitumour activities have been
      investigated. The compounds fall into two broad topological classes, where the
      carboxamide side chain is appended either to one of the terminal rings or to the
      central ring. In general, compounds of the first class showed stronger DNA
      binding than those of the second, and were the more potent in vitro cytotoxins.
      However, they were considerably less effective than DACA, both as DNA binders and
      cytotoxins. A 1,10-phenanthrolinecarboxamide derivative showed significant in
      vivo activity. As a class, these fused angular tricyclic carboxamides do not show
      sufficiently interesting activity to warrant further studies.

PMID- 8286012
TI  - Heterocyclic mono-N-oxides with potential applications as bioreductive anti
      tumour drugs: Part 1. 8-Alkylamino-substituted phenylimidazo [1,2-a]
      quinoxalines.
AB  - A series of imidazo [1,2-a] quinoxaline mono-N-oxides and their 6- and 9-aza
      analogues have been substituted in the 8-position with a variety of secondary and
      tertiary amines, and the compounds evaluated as bioreductively activated
      cytotoxins. Cytotoxic action against hypoxic cells in vitro was critically
      dependent upon the structural nature of the 8-substituent and its basicity, with
      little dependence upon reduction potential. 1,2-Dihydro-8-(4-methylpiperazin-1
      yl)-4-phenylimidazo [1,2-a] pyrido [3,2-e] pyrazine 5-oxide (11) had differential
      hypoxic:oxic toxicity of 15.3 and some novel analogues had differential
      hypoxic:oxic toxicities of 7.5-17. Other related compounds with either
      substituted or unsubstituted 8-piperazinyl substituents, or certain straight
      chain aminoalkyl substituents, show comparable activity in vitro. Less basic 8
      substituents abolished activity, although the 8-morpholinyl derivatives (7 and 8)
      had differential hypoxic:oxic toxicities of 3-4. Substitution of the 4-phenyl
      ring with an electron-withdrawing group (F) improved hypoxic potency, but only
      with a small effect on hypoxic:oxic toxicity, whereas an electron-donating
      substituent (MeO) reduced hypoxic potency. Perhaps significantly, the 8
      unsubstituted analogue 3 was 6-fold less potent, but had comparable differential
      cytotoxicity in vitro. The most effective novel hypoxia-selective cytotoxins
      synthesized were the bifunctional 2-nitro-imidazole derivative 1,2-dihydro-8-((4
      (3-(2-nitro-1-imidazoyl)-1-hydroxypropyl)- piperazin-1-yl))-4-phenylimidazo [1,2
      a] quinoxaline 5-oxide bishydrochloride (37) and its 9-aza analogue 38. These
      compounds also exhibited the lowest aerobic toxicities in vitro of the new
      compounds.

PMID- 8286013
TI  - Clinical trials with intraperitoneal cisplatin microspheres for malignant ascites
      -a pilot study.
AB  - A new formulation (CDDP-MS), which is composed of lactic acid oligomer
      microspheres incorporating cisplatin, has been developed in a dosage form for
      peritoneal carcinomatosis. In this pilot study, CDDP-MS was used clinically for
      the treatment of malignant ascites induced by cancers of the digestive organs.
      Thirteen patients with malignant ascites received an i.p. administration of CDDP
      MS, of which 12 received 100 mg and one received 200 mg of cisplatin/person to
      control the ascites. Total platinum levels in ascites and blood plasma were
      measured periodically. Intraperitoneal CDDP-MS decreased malignant ascites
      completely in eight patients and partially in four patients, and thus gave a
      response rate of 92%. The platinum concentration in ascites was maintained at a
      high level for a week after administration, whereas the concentrations in blood
      plasma were low. The side effects were well tolerated. Intraperitoneal CDDP-MS
      exhibits a marked therapeutic benefit with small systemic side effects for the
      treatment of malignant ascites.

PMID- 8286014
TI  - Uptake and photoeffectiveness of two thiazines in HeLa cells.
AB  - A comparative study of the uptake and photoinactivation of HeLa cells treated
      with methylene blue (MB) and toluidine blue (TB) has been performed. Cell
      toxicity induced by different concentrations of either MB or TB showed that 10(
      5) M was the concentration at which dark damage was not observed, while an
      elevated photoinactivation could be detected with both thiazines. The uptake
      studies showed that the penetration kinetics of 10(-5) M MB into HeLa cells is
      faster than that of TB, used at the same concentration, reaching saturation
      (approximately 1.8 micrograms/10(6) cells) after 6 or 12 h of incubation,
      respectively. For both sensitizers, the survival of HeLa cells was dependent on
      the incubation time, as well as the light dose, for a given concentration (10(-5)
      M). Moreover, cell photoinactivation produced by MB was higher than that produced
      by TB. The differences between MB and TB obtained under our experimental
      conditions are discussed.

PMID- 8286015
TI  - On calculating incidence rate.

PMID- 8286016
TI  - NPUAP update on reimbursement.

PMID- 8286017
TI  - Pressure ulcer prevalence, incidence and associated risk factors in the
      community.
AB  - This study examined the prevalence and incidence of pressure ulcers as well as
      associated risk factors in the community. By using the Web of Causation and the
      Braden conceptual schema, barriers to effective interventions were identified and
      analyzed. The Web of Causation for pressure ulcer development includes
      socioeconomic factors and personal belief systems. It also includes the following
      risk factors: mobility, activity, moisture, nutrition, friction, shear, and
      altered sensory perception. There were 103 participants in this study. Data
      gathered by public health nurses included occurrence, risk assessment score, and
      demographics. Significant demographics for the pressure ulcer group included age
      greater than 70 years and diagnoses related to altered mobility, activity, and
      circulatory status. Pressure ulcer patients who were incontinent accounted for
      73% of the total, with urinary incontinence accounting for 33%. There were 1.4
      ulcers per patient. Most of the ulcers (78%) occurred on the sacral/coccygeal
      area and were either Stage II or Stage III. The prevalence rate of pressure
      ulcers in the community was 29% and the incidence rate was 16.5%.

PMID- 8286018
TI  - Case study: the role of surgical debridement and dural patching in the prevention
      of a recurrent radiation-induced sacral ulcer.
AB  - The effects of radiation are not tissue selective. Changes are consistent with
      thermal injury, but evolve in a more insidious manner. Erythema, edema, itching,
      and osteonecrosis can occur. These changes, over the sacrum, can lead to a spinal
      cutaneous fistula with persistent cerebrospinal fluid (CSF) leak in association
      with ulceration. Soft tissue coverage alone appears to be inadequate treatment.
      Aggressive bony debridement with dural patching have prevented recurrence of the
      fistula in a recent case.

PMID- 8286019
TI  - Skin failure and the pressure ulcer.

PMID- 8286020
TI  - A comparative study of wound dressings on full-thickness wounds in micropigs.
AB  - Eight full-thickness (to the depth of adipose tissue) skin wounds were surgically
      inscribed on the backs of four Yucatan micropigs (32 wound sites in total). Wound
      sites were created to allow for controlled comparative evaluation between wound
      sites, wound dressings, and specified postoperative healing time. The wounds were
      dressed with either ClearSite hydrogel dressing (New Dimensions in Medicine,
      Dayton, Ohio) or Duoderm hydrocolloid wound dressing (ConvaTec Inc., Princeton,
      New Jersey). Tracings and photographs of each wound site were made and
      computerized planimetry was done to compare the rate of epithelialization for
      like wounds and like wound dressings. Histomorphometric measurements were also
      made to compare the effects of the dressing on the wounds at the cellular level.
      The results of this study indicate that the wounds covered with the hydrogel
      dressing exhibited a more rapid rate of closure and reepithelialization as
      compared with the hydrocolloid wound dressing.

PMID- 8286021
TI  - Measurement strategies: the visual analogue scale.
AB  - Measuring psychosocial responses to health problems poses a unique challenge for
      the clinician searching for empirical indicators of these abstract constructs.
      Subjective phenomena such as pain, craving, or well-being vary in levels of
      intensity and are often difficult for the individual to describe in concrete
      terms. Visual analogue scales provide a valid and reliable solution to this
      challenging measurement problem.

PMID- 8286022
TI  - Questions about staging.

PMID- 8286023
TI  - The effects of prolonged pressure on skin blood flow in elderly patients at risk
      for pressure ulcers.
AB  - Although the physiological effects of pressure on tissue have been demonstrated
      in the animal model, little is known about its effect in ill, elderly patients
      who are at risk for pressure ulcers. This study describes the pattern of dermal
      blood flow during a period of constant, low-level, compressive pressure in this
      population of patients. Dermal blood flow was measured over the trochanter of 16
      elderly (> 60 years) subjects who were defined as at risk for pressure ulcer
      development by the Braden Scale for Predicting Pressure Ulcer Risk. Using a laser
      Doppler velocitometer, blood flow at baseline and during 60 minutes of left-side
      lying on an air mattress were measured. Mean blood flow at baseline was 0.79 (SD
      0.43). Following 60 minutes of compressive pressure, mean blood flow was 0.65 (SD
      0.87). Blood flow tracings during the 60-minute period of continuous, compressive
      pressure revealed an inconsistent pattern of response; the flow increased,
      decreased, or showed no change. This distribution of responses suggests that
      significantly more variability in blood flow response exist in at-risk
      individuals than was previously believed.

PMID- 8286024
TI  - Comparison of quantitative methodologies to define chronic pressure ulcer
      measurements.
AB  - The objective of this study was to evaluate and compare various methodologies of
      measuring the characteristics of pressure ulcers. This prospective, four-week,
      follow-up study consisted of 20 patients, of whom 17 completed the study. Each
      patient had at least one full-thickness pressure ulcer (surface area between 1.2
      and 61.6 cm2) that had been present for at least four weeks. The ulcers were
      assessed weekly for four weeks using the following techniques: direct measurement
      (length, width, and depth), tracing of the ulcer outline onto transparent
      material, standard photography, and volume measurement. Computer-assisted
      planimetry from the tracings and photographs, and calculations from the direct
      measurements determined ulcer areas. Each technique estimating ulcer area gave
      similar results; however, the areas obtained from the direct measurements
      slightly over-estimated the areas when compared with the areas obtained by
      computer-assisted planimetry (mean difference of about 1.5 cm2). Areas obtained
      from the photographs were more variable than the other measurement techniques.
      Volumes calculated from bedside measurements were consistently larger than those
      calculated by jeltrate impression (mean difference of 4.0 cm3). While all the
      measurement methodologies gave similar and reproducible results, the areas
      obtained from the photographs were more variable than the areas obtained from the
      other measurement techniques. The photographic measurements could be improved
      either by tracing the ulcer outline at the bedside onto the photograph shortly
      after being taken, or by drawing an outline of the ulcer margin directly on the
      patient's skin just before taking the photograph.

PMID- 8286025
TI  - Specialty support surfaces: a cost containment perspective.
AB  - Challenged by annual expenditures exceeding $5.9 million dollars for specialty
      support surface rentals, the National Center for Cost Containment (NCCC), an
      office of the Department of Veterans Affairs (VA), organized a Technical Advisory
      Group (TAG) to identify strategies for the appropriate use and cost-containment
      of specialty support surfaces. A survey of utilization patterns revealed that
      some VA facilities (n = 20) had no expenditures for rental of specialty support
      surfaces while others (n = 13) spent over $100,000 per facility on rental
      expenditures. Many facilities had a significant cost savings by owning specialty
      support surfaces. A decision-making tree, emphasizing first line devices, was
      developed to assist in containing expenditures. It was recommended that this
      algorithm be used in conjunction with the Specialty Support Surface Guidelines
      developed by the TAG. It is anticipated that this information may assist both VA
      and non-VA healthcare facilities to contain costs in the utilization of specialty
      support surfaces.

PMID- 8286027
TI  - Skin failure and the pressure ulcer.

PMID- 8286026
TI  - A comparison of Epi-Lock and saline dressings in the treatment of pressure
      ulcers.
AB  - The use of Epi-Lock dressings was compared to moist saline dressings as a
      treatment for Stage II and III pressure ulcers in 38 patients. Demographic and
      clinical data were collected at the onset of the investigation. At the time of
      enrollment and during weeks six, 12 and 24, pressure ulcers were inspected and
      measured, and laboratory data were collected. More healing occurred with Epi-Lock
      dressing than with moist saline dressing for Stage II and III pressure ulcers.
      Although individual Epi-Lock dressings were more expensive than saline dressings,
      they required less dressing changes. Therefore considering cost of nursing time,
      Epi-Lock dressings are more cost effective.

PMID- 8286028
TI  - A quantitative study of normal nephrogenesis in the human fetus: its implication
      in the natural history of kidney changes due to low obstructive uropathies.
AB  - An evaluation of nephrogenesis according to fetal age was performed by
      quantifying the state of the nephrogenic blastema (NB) and the number of
      glomeruli (GN) on frontal renal sections in 99 control fetuses (gestational age
      ranging from 9 to 40 weeks) and in 17 aborted fetuses with low urinary tract
      obstruction (gestational age ranging from 14 to 36 weeks). In the control group,
      GN increases slowly from the 10th to the 18th week, then abruptly from the 18th
      to the 32nd week, reaching an upper limit with NB disappearance by the 32nd week.
      In the uropathy group, the renal changes show a wide range of severity clearly
      accounted for by the impairment of both NB and GN. The dysplastic effect of
      urinary backpressure is the more consistent pathogeny with the spectrum of
      observed renal changes. It is likely, from GN used as a time-dependent marker of
      renal development, that the most severe dysplasia is the result of early
      obstruction with abnormal disappearance of NB and subsequent arrest of
      nephrogenesis.

PMID- 8286029
TI  - Comparison of intrapartum fetal monitor tracings of karyotypically abnormal and
      control infants.
AB  - To determine if there are any specific monitoring patterns associated with
      chromosomal abnormalities the intrapartum tracings of 17 postnatally diagnosed
      karyotypically abnormal infants were obtained. Controls were randomly selected
      from infants born on the same day at the same gestational age. The tracings from
      these two groups were independently evaluated. Comparison of the monitor
      interpretations showed: (1) the karyotypically abnormal group was more likely to
      have decreased or absent short- (p < 0.001) and long-term (p < 0.01) variability;
      (2) accelerations were more likely to be represented in the control group (p <
      0.001); (3) no significant differences were found in the baseline heart rates or
      in the presence or frequency of mild, moderate, or severe variable or late
      decelerations. These findings may reflect underlying central nervous system
      abnormalities as opposed to uteroplacental insufficiency, but are not specific to
      karyotypically abnormal infants.

PMID- 8286030
TI  - How antenatal ultrasound diagnosis of congenital malformations has contributed to
      fetal outcome: a 22-year review.
AB  - We herein reviewed 630 malformed fetuses delivered from 24 weeks of gestation
      onwards in our institute over the past 22 years. These fetuses were divided into
      2 groups: 210 from 1970 to 1982 (group 1) and 420 from 1983 to 1991 (group 2).
      Twenty-two varieties of congenital malformations were diagnosed antenatally in
      group 1, whereas 55 additional malformations became diagnosable in group 2.
      Thirty-four varieties of congenital malformations still remained undiagnosed
      throughout the 22-year study period. Cases receiving 'fetal therapy' and 'close
      obstetric care' increased, with statistical significance, from 1.8 to 15.7%, and
      from 22.9 to 55.7% in groups 1 and 2, respectively. A significant increase was
      also noted in the survival rate from group 1 (63.3%: 105/166) to group 2 (75.5%:
      259/343). This study has revealed that the steady advancement in antenatal
      diagnosis of congenital malformations, along with great efforts in terms of
      intensive care, has contributed to improved fetal outcome.

PMID- 8286031
TI  - Fetal growth and birthweight in isoimmunized pregnancies after intravenous
      intrauterine transfusion.
AB  - Forty-seven fetuses treated with intravenous intrauterine transfusion for rhesus
      isoimmunization were studied. At the time of first transfusion the fetuses were
      below average in size with the fetal femur length being directly related to the
      degree of fetal anemia. Subsequent to transfusion therapy there was increased
      growth of all fetal parameters measured. Birthweight was similar to a control
      group of unaffected fetuses. This contrasts with results after intraperitoneal
      transfusion where birthweights have been reported as being below average.

PMID- 8286032
TI  - Transabdominal amnioinfusion for the management of nonlaboring postdates with
      severe oligohydramnios.
AB  - A retrospective study compared two comparable consecutive groups of nonlaboring
      primiparas beyond 41 weeks with severe oligohydromanios (no amniotic pocket more
      than 2 cm deep). Transabdominal amnioinfusions were not done in the historical
      control group (n = 14) but were done in the second group (n = 11). Fetal heart
      rate patterns and neonatal outcome were better in the group with amnioinfusion
      than in controls, and the rate of cesarean delivery was significantly lower (18
      vs. 93%, p < 0.001). These results suggest that prepartum transabdominal
      amnioinfusion may have obstetrical and perinatal benefits for nonlaboring
      postdates with oligohydramnios, especially when the cervix is unripe.

PMID- 8286033
TI  - Perinatal case report of unexpected thalassemia Hb Bart.
AB  - Homozygous alpha-thalassaemia Hb Bart is a very rare illness in North America and
      Western Europe, but is a common cause of NIHF especially in South East Asia. It
      causes severe hydrops fetalis with lethal outcome and maternal complications as
      preterm labour, pre-eclampsia and retained placenta. A case report of an
      immigrant from Laos with preterm labour and fetal ascites, but without signs of
      pre-eclampsia is demonstrated. Fetal heart rate (FHR) trace and biophysical
      profile were pathological, while umbilical Doppler flow was normal due to
      hypoxaemia, but with hypervolumina and a high cardiac output. An amniocentesis
      and puncture of the ascites were performed, but FBS was not successful. Before
      receiving the results a caesarean section had to be done for deterioration of the
      FHR trace. A 1,370-g female infant was born who died of cardiovascular failure
      due to an alpha-thalassaemia Hb Bart and respiratory distress 5 days post partum.
      The parents had both an alpha-zero-thalassaemia. alpha-Thalassaemia is still a
      very unknown illness in Germany, but with the increasing numbers of immigrants
      from South East Asia it should be considered at the differential diagnosis of
      hydrops fetalis. A prenatal diagnosis should be offered to parents with alpha
      zero-thalassaemia.

PMID- 8286034
TI  - Meroanencephaly: pathology and prenatal diagnosis.
AB  - Meroanencephaly is a rare form of anencephaly characterized by malformed cranial
      bones and a median cranial defect, through which protrudes abnormal tissue,
      called the area cerebrovasculosa. Area cerebrovasculosa denotes abnormal spongy,
      vascular tissue admixed with glial tissue ranging from a thin membrane to a large
      pseudoencephalic mass simulating cerebral tissue, that is composed of connective
      tissue, hemorrhagic vascular channels, glial nodules, and disorganized choroid
      plexuses. There are three types of anencephaly: (1) meroanencephaly, where there
      is rudimentary brain tissue and partial formation of the cranium; (2)
      holoanencephaly, the most common type, in which the brain is completely absent,
      and (3) craniorachischisis, the most severe, where area cerebrovasculosa and area
      medullovasculosa fill both cranial defects and the spinal column. In
      meroanencephaly, there is a median defect present, through which protrudes the
      area cerebrovasculosa. We present 3 cases of meroanencephaly diagnosed
      prenatally, along with histopathologic analysis. One case showed ectopic glial
      tissue in the lung and adrenal medullary hyperplasia. Two cases were diagnosed in
      the early second trimester by ultrasound scanning. Meroanencephaly may be
      mistaken for encephalocele both at the bedside exam and sonographically, and
      should be included in the differential for protruding anterior cranial masses.

PMID- 8286035
TI  - Cloning of the gene for bovine monocyte chemoattractant protein-2.
AB  - Bovine monocyte chemoattractant protein-1 (bovine MCP-1) cDNA has recently been
      characterized and shown to be highly expressed in bovine seminal vesicles
      secretory epithelium as well as in phytohemagglutinin (PHA)-stimulated peripheral
      blood mononuclear leukocytes (PMNLs). In an attempt to isolate the MCP-1 gene, we
      screened a bovine genomic cosmid library with a MCP-1-specific probe pH42. A
      positive clone, c11/1, was subjected to restriction analysis and fragments probed
      with pH42 by southern blotting. pH42-positive fragments were subcloned and
      sequenced. The sequence revealed three exon-like regions that coded for a protein
      displaying an identity of 51% with bovine MCP-1. Employing this sequence
      information from c11/1, the c11/1-specific cDNA was generated from poly(A)+RNA of
      bovine PMNLs by reverse transcription and a combination of polymerase chain
      reaction (PCR) methods. The assembled c11/1 cDNA comprised a 5' UTR coding region
      as well as 3' UTR for the gene product c11/1. Amino acid sequence comparison of
      the bovine c11/1 gene product with human monocyte chemotactic proteins yielded
      the highest sequence identity with human MCP-2, and it is assumed that the c11/1
      gene product represents the bovine MCP-2. The exon/intron structure of the bovine
      MCP-2 gene was found to be similar to the human MCP-1 gene. The bovine MCP-2 gene
      consists of three exons separated by two introns. In the 5'-flanking region of
      the 3.3-kb gene, a TATA box as well as an AP-1 sequence motif were identified.
      The bovine MCP-2 is specified by a single-copy gene.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8286036
TI  - Cloning and characterization of hamster proenkephalin gene.
AB  - Our previous studies have shown that the hamster adrenal, like the human,
      contains high levels of preproenkephalin (PPenk) mRNA and enkephalin peptides,
      and may serve as a mammalian model for the in vivo study of proenkephalin (Penk)
      gene expression, peptide biosynthesis, and release. To define further the factors
      that may regulate hamster Penk gene expression, the hamster Penk gene was
      isolated from a genomic library prepared from Syrian hamster liver. The hamster
      Penk gene contains four exons and three introns and encodes 268 amino acids
      including six copies of Met-enkephalin containing peptides and one copy of Leu
      enkephalin. In the 5' upstream region, there are TATA and GC boxes and multiple
      putative regulatory elements including the cAMP response element, AP-1, AP-2, AP
      4, and the glucocorticoid response element (GRE). Possible GREs are also present
      in the introns. A comparison with the human and the rat Penk genes indicates that
      both the human and hamster Penk gene contain three introns, while the rat Penk
      gene has two introns. The intron missing from the rat Penk gene is short and
      separates the first and second exons of the hamster and human genes. In addition,
      the hamster and human genes share a region (100 bases) in the 5' upstream
      sequence that is 98% homologous. It is of interest that Penk gene expression is
      high in the adrenal medulla of both human and hamster, but is much lower in the
      rat. These homologous regions and the extra intron may contain regulatory
      features responsible for a high level of expression in the human and hamster
      adrenal medulla.

PMID- 8286037
TI  - Cloning and characterization of the bovine immunoglobulin J chain cDNA and its
      promoter region.
AB  - The immunoglobulin J (joining) chain plays an important role in the assembly of
      polymeric immunoglobulins (dimeric IgA and pentameric IgM) and in the selective
      transport of these across epithelial cell layers. The primary structure of the
      bovine J chain has been determined by sequencing of three cDNAs. The cDNA has an
      open reading frame of 471 nucleotides encoding a putative protein of 157 amino
      acids. The 3' untranslated region consists of 698 nucleotides and a poly(A) tail.
      The 5' untranslated region and the promoter were isolated from a genomic clone.
      By comparison with the murine J chain gene, the 5' untranslated region was
      predicted to be 37 bp, giving the bovine J chain cDNA a total length of 1,206 bp.
      This size was confirmed by Northern blot analysis of total RNA from colon and
      mammary gland. The amino acid sequence of the bovine J chain shows extensive
      homology with the J chain from human, mouse, rabbit, and bullfrog. Analysis of
      the J chain secondary structure showed a high propensity for forming beta-sheets.
      An alignment of the predicted secondary structure of the J chain from bovine,
      human, mouse, rabbit, and bullfrog revealed a highly conserved "beta-profile."
      The promoter sequence of the bovine J chain gene is presented and shown to
      contain a conserved interleukin-2 (IL-2)-responsive element previously
      characterized in the murine J chain gene.

PMID- 8286038
TI  - Hepatic transcriptional up-regulator of the rat microsomal epoxide hydrolase
      gene.
AB  - Rat microsomal epoxide hydrolase (mEH) is one of the detoxification enzymes and
      selectively expressed in liver. A 350-bp DNA fragment of the proximal promoter
      was found to contain information sufficient to express the mEH gene in hepatoma
      cells, however not in nonhepatoma cells. We identified two cis-acting elements,
      epoxide hydrolase proximal element 1 (EHP1) and 2 (EHP2), in this promoter region
      by using transient transfection assays. Each element is a new cell-type-specific
      transcriptional up-regulator. The cell-type-specific activity of EHP1 correlates
      to the limited cell distribution of its cognate transacting factor(s). In the
      case of EHP2, a similar or possibly the same cognate factor(s) binding to EHP2
      was detected by DNase I footprinting and gel retardation assays in both hepatoma
      and nonhepatoma cells. However, EHP2 functions as an up-regulator only in
      hepatoma cells. Our finding adds repertoire to a battery of cis-regulatory
      elements that are required for liver-specific transcription.

PMID- 8286039
TI  - Effect of artificially inserted intron on gene expression in Saccharomyces
      cerevisiae.
AB  - The intron of the yeast RP51A gene was cloned with precision using the polymerase
      chain reaction (PCR) amplification method, and then inserted into several
      different positions of the yeast URA3 gene as well as the PGK-lacZ fusion gene
      without introduction of additional exon sequences. Analysis of transcripts of
      these genes showed that an intron inserted near the transcription start site of
      the gene was spliced out efficiently, whereas the same intron sequences inserted
      200 bp or further downstream of the start site were not, resulting in a reduced
      level of mRNA. These results explain why intron-containing genes in yeast usually
      have an intron near the 5' end.

PMID- 8286040
TI  - Chemoprevention of retroviral infection: success is determined by virus inoculum
      strength and cellular immunity.
AB  - We demonstrated earlier that post-exposure prophylaxis with 3'-azido-3'
      deoxythymidine (AZT, zidovudine) or with AZT + interferon-alpha (IFN-alpha)
      prevented viremia and disease in BALB/c mice inoculated with Rauscher murine
      leukemia virus (RLV). After the 20-day treatment course, most animals were
      resistant to rechallenge with live virus. Adoptive transfer of T cells from such
      resistant but not from normal mice into naive recipients provided full protection
      against virus challenge. From these experiments, we concluded that post-exposure
      chemoprophylaxis restricted virus replication and allowed the animals to form
      protective, long-lasting cellular immune responses. Here, the role for cellular
      immunity during antiviral chemoprophylaxis was tested by comparing treatment
      success in normal BALB/c mice and in their nude, athymic counterparts. Both were
      inoculated with equal doses of RLV (10(4) plaque-forming units, pfu). Single
      agent AZT or combination therapy with AZT + IFN-alpha, started before or after
      RLV inoculation, prevented viremia in all normal but not in most nude mice. A
      significant number of nude mice were completely protected by chemoprevention only
      when given a 10 times lower virus dose. When normal mice were injected with a 10
      times higher virus dose (10(5) pfu), complete protection by chemoprevention was
      lost. These results demonstrate that the success of chemoprevention depends
      critically on the virus inoculum. The differential success of chemoprevention in
      normal and T-cell-deficient mice implies that effective cellular immunity plays
      an important role in protecting virus-exposed animals against viremia and
      disease.

PMID- 8286041
TI  - Identification of a human immunodeficiency virus type 1 TAR binding protein in
      human hepatoblastoma HepG2 cells that trans-activates HIV-1 LTR-directed gene
      expression.
AB  - Recently, we have shown that the human immunodeficiency virus (HIV-1) long
      terminal repeat (LTR) directed chloramphenicol acetyltransferase (CAT) gene is
      efficiently expressed in human hepatoblastoma HepG2 cells and these cells can
      support productive HIV-1 replication. In this study we show that HepG2 cells
      contain a nuclear factor that binds to the HIV-1 trans-activating region (TAR),
      which we named HepG2-derived TAR binding protein (HTBP). Gel retardation assays
      using synthetic oligonucleotide probes carrying different mutations in the TAR
      region and competition DNA mobility-shift experiments using these
      oligonucleotides revealed the binding site encompassing between +7 and +13
      nucleotides (5'-TCTGGTT-3') in the HIV-1 LTR. An in vivo CAT competition assay
      using -65HIV-1 LTR CAT as a reporter plasmid and various competitor plasmids
      containing these mutated oligonucleotides also demonstrated that HTBP can
      influence the HIV-1 LTR-directed CAT gene expression in HepG2 cells by
      interaction with a specific sequence in the TAR region.

PMID- 8286042
TI  - Oligonucleotides as short as 7-mers can be used for PCR amplification.
AB  - Amplification of DNA sequences using the polymerase chain reaction (PCR) requires
      as primers two oligonucleotides, which are carefully designed for length and G/C
      content. Such primers are generally between 18 and 30 bases long so that the
      primer sequences can amplify a unique sequence in the target genome; they should
      possess a minimal degree of secondary structure. We have tested the minimum
      length of G/C-rich and palindromic oligonucleotides to be used as primers in PCR.
      Oligonucleotides with sequences corresponding to the recognition sites of rare
      restriction enzymes were used on the DNA of vector constructs as model template
      DNA. Surprisingly, we found specific amplification with a low background over a
      wide range of temperatures for oligonucleotides as short as 7 nucleotides. This
      findings contradicts the previously reported empirical relationship between
      oligonucleotide length and ability to trigger amplification and points to the
      complex relationship between thermodynamic and kinetic criteria in relation to
      PCR. This technique should lead to new application in the cloning and screening
      of complex genomes.

PMID- 8286043
TI  - An efficient method for large-scale isolation of plasmid DNAs by heat-alkali co
      denaturation.
AB  - A method is presented for efficient and large-scale isolation of plasmid DNAs
      from bacterial cells. Based on the cooperativity of heat and alkali actions, the
      method provides DNA preparations with high quality and yield (about 2 micrograms
      of DNA/ml culture), which are completely digestable by restriction enzymes and
      have a high transformation efficiency. Furthermore, the DNA preparations are
      extremely stable, and even through 4-year storage at -20 degrees C, the
      electrophorogram and transformation efficiency remain as high as before. The
      factors affecting the stability of various DNA samples are discussed.

PMID- 8286044
TI  - Molecular cloning and functional analysis of the promoter of rat skeletal muscle
      voltage-sensitive sodium channel subtype 2 (rSkM2): evidence for muscle-specific
      nuclear protein binding to the core promoter.
AB  - rSkM2 is a tetrodotoxin-resistant rat skeletal muscle voltage-sensitive sodium
      channel that is expressed in immature and denervated skeletal muscle and in adult
      heart. We have isolated a 3.7-kb gene segment that contains the first exon,
      multiple transcription initiation sites, the core promoter (nt -102 to +1), GC
      rich elements (Sp1 recognition sites), three overlapping C-rich motifs (important
      for muscle-specific expression of some muscle genes), and multiple CANNTG (E-box)
      motifs (MyoD binding sites). A deletion analysis of the 5' upstream 2.8-kb
      segment, driving the rSkM2 core promoter, has localized a muscle-restrictive
      enhancer element (MRSE) at least 2 kb upstream from the core promoter. The core
      promoter is silenced by an additional cis element (-645/-506). The positive and
      negative cis-elements together drive transcription of the chloramphenicol
      acetyltransferase (CAT) reporter gene from the core promoter at about the same
      level as does the core promoter alone in a skeletal muscle differentiation stage
      specific manner. Gel-shift assays have identified sequence- and cell-type
      specific proteins that bind to a 16-bp region (-44/-29) containing C-rich motifs.
      Muscle-specific complexes formed from muscle cell nuclear extracts and a 16-bp
      element (-44/-29) are competed by unlabeled -44/-29 oligonucleotide but not by
      several mutant oligonucleotides that implicate nucleotides -40 to -38 and -34 to 
      32 in the binding of a nuclear protein (designated SkM2 transcription factor 1,
      SkM2-TF1). We conclude that rSkM2 gene expression depends on the interactions of
      positive and negative transcriptional regulators with tissue- and developmental
      stage-specific core promoter elements.

PMID- 8286045
TI  - [Poverty and inattention].

PMID- 8286046
TI  - [Tuberculosis: not a 'conquered' disease].

PMID- 8286047
TI  - [Nursing of patients with tuberculosis].

PMID- 8286048
TI  - [Maturing in the nursing home].

PMID- 8286049
TI  - [Introduction and use of standard nursing care plans].

PMID- 8286050
TI  - [Standard nursing care plans behave like an oil slick. Interview by Toine de
      Graaf and Tonny van de Pasch].

PMID- 8286051
TI  - [Elderly patients force someone to adapted education].

PMID- 8286052
TI  - A model for the solution structure of a branched, three-strand DNA complex.
AB  - The solution structure of a DNA three-way junction (TWJ) containing two unpaired
      thymidines was elucidated using two- and three-dimensional 1H nuclear magnetic
      resonance (NMR) spectroscopy. TWJs with unpaired nucleotides are ubiquitous
      structural motifs of complex single-stranded nucleic acids. In the presence of
      Mg2+, the TWJ complex adopts a unique conformation in which the bases of one of
      the oligonucleotides ("strand 1") are continuously stacked across the junction.
      Guanosine 8 of strand 3 (S3-G8), which pairs with S1-C5, stacks on S2-G5, which
      is paired to S1-C6. The unpaired thymidine bases (S3-T6 and S3-T7) are exposed to
      the solvent, whereas the sugar of S3-G8 is largely buried. S3-T6 also interacts
      with the sugar residue of S3-G11. All three stems conform to B-type DNA.

PMID- 8286053
TI  - Molecular dynamics investigations of DNA triple helical models: unique features
      of the Watson-Crick duplex.
AB  - We have built computer models of triple helical structures with a third poly(dT)
      strand Hoogsteen base paired to the major groove of a poly(dA).poly(dT) Watson
      Crick (WC) base-paired duplex in the canonical A-DNA as well as B-DNA. For the A
      DNA form, the sugar-phosphate backbone of the third strand intertwines and
      clashes with the poly(dA) strand requiring a radical alteration of the duplex to
      access the hydrogen bonding sites in the major groove. In contrast, when the
      duplex was in the canonical B-DNA form, the third strand was readily accommodated
      in the major groove without perturbing the duplex. The triple helical model, with
      the duplex in the B-DNA form, was equilibrated for 400ps using molecular dynamics
      simulations including water molecules and counter-ions. During the entire
      simulations, the deoxyriboses of the adenine strand oscillate between the S-type
      and E-type conformations. However, 30% of the sugars of the thymine strands-II &
      III switch to the N-type conformation early in the simulations but return to the
      S-type conformation after 200ps. In the equilibrium structure, the WC duplex
      portion of the triplex is unique and its geometry differs from both the A- or B
      DNA. the deoxyriboses of the three strands predominantly exhibit S-type
      conformation. Besides the sugar pucker, the major groove width and the base-tilt
      are analogous to B-DNA, while the X-displacement and helical twist resemble A
      DNA, giving a unique structure to the triplex and the Watson & Crick and
      Hoogsteen duplexes.

PMID- 8286054
TI  - Thermodynamic and kinetic analyses of DNA triplex formation: application of
      filter-binding assay.
AB  - We have developed a simple and efficient method for studying equilibrium
      thermodynamics and kinetics of DNA triplex formation, which utilizes a filter
      binding procedure. The application of this method to the triplex formation
      between a double-stranded homopurine-homopyrimidine and a single-stranded
      homopyrimidine oligonucleotides has demonstrated its ability in the quantitative
      estimation of equilibrium binding constants and rate constants under various
      conditions. Thus, this simple method can serve as a powerful tool for the
      systematic analysis of sequence and environmental effects on the equilibrium and
      kinetic quantities in the triplex formation.

PMID- 8286055
TI  - Molecular structure of cyclic diguanylic acid at 1 A resolution of two crystal
      forms: self-association, interactions with metal ion/planar dyes and modeling
      studies.
AB  - Cyclic ribodiguanylic acid, c-(GpGp), is the endogenous effector regulator of
      cellulose synthase. Its three dimensional structure from two different crystal
      forms (tetragonal and trigonal) has been determined by x-ray diffraction analysis
      at 1 A resolution. Both structures were solved by direct methods and refined by
      block-matrix least squares refinement to R-factors of 0.112 (tetragonal) and
      0.119 (trigonal). In both crystal forms, two independent c-(GpGp) molecules
      associate with each other to form a self-intercalated dimer. All four c-(GpGp)
      molecules have very similar backbone conformation. The riboses are in the C3'
      endo pucker with pseudorotation angles ranging from -7.2 degrees to 16.5 degrees
      and the bases have anti glycosyl chi angles (-175.5 degrees to 179.7 degrees). In
      the tetragonal form, a hydrated cobalt ion is found to coordinate to two N7 atoms
      of adjacent guanines, forcing these two guanines to destack with a large dihedral
      angle (33 degrees). This metal coordination mechanism has been noted previously
      in other Pt- or Co-GMP complexes and may be relevant to the binding of the
      anticancer drug cisplatin to a GpG sequence in DNA. A model of the adduct between
      cisplatin and a d(CAATGGATTG) duplex has been constructed in which the induced
      bending of the DNA helix at the Pt crosslinking site is 33 degrees, consistent
      with earlier electrophoretic analyses. Moreover, c-(GpGp) exhibits unusual
      spectral properties not seen in other cyclic dinucleotides. It interacts with
      planar organic intercalator molecules in ways similar to double helical DNA. We
      propose a cage-like model consisting of a tetrameric c-(GpGp) aggregate in which
      a large cavity (host molecule) is generated to afford a binding site for certain
      planar intercalators (guests molecules). The aggregate likely uses a hydrogen
      bonding scheme the same as that found in the G-quartet molecules, e.g., telomere
      DNA. The conformation of c-(GpGp) also suggests that certain nearest-neighbor
      intercalators may be synthesized on the basis of its unique molecular framework.
      Modeling studies have been carried out to test this hypothesis.

PMID- 8286056
TI  - Theoretical analysis of the base stacking in DNA: choice of the force field and a
      comparison with the oligonucleotide crystal structures.
AB  - It follows from previous studies that changes in the base pair vertical
      separation (BPVS) influence the architecture of DNA much more than any other
      conformational parameter. This inspired us to compare BPVS in the available
      oligonucleotide crystal structures with the optimum values provided by nine
      different empirical potentials employed in the theoretical studies of DNA
      conformation. This comparison shows that BPVS is reproduced by three fields in
      all steps of the highly resolved oligonucleotide crystal structures while the
      remaining six empirical potentials, including AMBER, GROMOS and CHARMM, provide
      systematic deviations. We further find that the base pairs are poorly stacked
      (mostly compressed) in some other refined DNA crystal structures. Our analysis
      indicates that this poor stacking originates from improperly determined positions
      of the bases. The approach described in the present communication can be used to
      identify DNA structures which are not accurate enough for studies of the
      relationships between the base sequence and DNA conformation.

PMID- 8286057
TI  - Conformations of DNA duplexes containing 8-oxoguanine.
AB  - As a step towards elucidating the mechanisms of mutagenesis induced by
      irradiation and oxidation, we study the incorporation of 8-oxoguanine (OG) into
      duplex DNA. Molecular modelling is used to reveal changes in DNA conformational
      parameters due to mispairs within the sequences d(A5XA5).d(T5YT5) and
      d(G5XG5).d(C5YC5) where one of the bases of the bases of the central X:Y pair is
      OG and the other A,T,G or C. The G:C to OG:C replacements in DNA duplexes produce
      only minor conformational changes, similar to normal base sequence effects. The
      calculations suggest that both OG(syn):G and OG(syn):A mispairs can also be
      introduced without drastic distortion of sugar-phosphate backbone. The
      distortions produced by OG-containing mispairs are also found to be sequence
      dependent. Overall these calculations suggest that the G-->OG conversion could be
      an important factor in the irradiative or oxidative damage of DNA.

PMID- 8286058
TI  - Free energy component analysis: application to the "Z-phobicity" of A-T base
      pairs.
AB  - We have carried out molecular dynamics/free energy perturbation calculations on
      the double helical hexamer d(CGCGCG)2 in both B and Z forms. The third C.G base
      pair was "mutated" to T-A in both B and Z-DNA. It is known experimentally that
      replacement of a C.G with a T-A base pair in an alternating CG sequence raises
      the energy of the Z form relative to the B form by approximately 1 kcal mole-1.
      We have carried out free energy component calculations to assess the reason for
      the "Z-phobicity" of T-A base pairs. There are two major contributions. The
      primary contribution is from the intra-base pair interactions of the mutated base
      pair itself which disfavor T-A relative to C.G in the Z form by congruent to 1.4
      kcal mole-1. A secondary contribution of 0.4 kcal mole-1 arises because the two
      cytosines on the strand where G is mutated to A disfavor T-A relative to C.G in
      the Z form by 1.9 kcal mole-1, while the guanines flanking the C on the
      complementary strand stabilize the T-A base pair relative to the C.G in the Z
      form by 1.5 kcal mole-1. The effect of the phosphates, non-neighboring
      nucleotides and intramolecular energies of the base pair being mutated are all
      small and come close to canceling each other, leading to a net calculated free
      energy for T-A Z-phobicity of 1.7 kcal mole-1.

PMID- 8286059
TI  - Cyclic voltammetry of submicrogram quantities of supercoiled, linear and
      denatured DNAs with DNA-modified mercury electrode.
AB  - We have previously shown that a DNA-modified electrode can be prepared by
      immersing the hanging mercury drop electrode (HMDE) in a small volume (about 5-10
      microliters) of a DNA solution. Within a short period of time the DNA is
      irreversibly adsorbed at the electrode, resisting subsequent washing. The
      electrode is then transferred into a voltammetric cell filled with the background
      electrolyte (that does not contain any nucleic acid) in which the voltammetric
      measurements are performed. This procedure is called adsorptive transfer
      stripping voltammetry (AdTSV). In this paper AdTS cyclic voltammetry (CV) peaks
      of DNA were measured to report on the stability of the attachment of plasmid DNA
      molecules to the electrode surface. It was shown that the attachment of plasmid
      DNA to the electrode was, like the case of calf thymus DNA, sufficiently stable.
      If the DNA-modified electrode was immersed in a protein solution no significant
      exchange between the DNA and protein was observed. Submicrogram amounts of DNA
      were sufficient to attain full coverage of the electrode at relatively short
      waiting times and the detection limit of the denatured DNA was below 2 ng. The
      intensity of the AdTS CV signals of supercoiled, linearized and thermally
      denatured linear DNAs differed from one another. It was shown that alkaline
      denaturation of linear and supercoiled DNA in solution can be studied using AdTS
      CV technique. It was further shown that at neutral pH the linearized plasmid
      undergoes denaturation due to a prolonged contact with the electrode charged to
      potentials around -1.2 V. Such a surface denaturation has been previously
      observed with calf thymus DNA and synthetic double-stranded polynucleotides. Our
      results show that in contrast to linear DNA, supercoiled DNA was not
      significantly denatured as a result of its prolonged contact with the electrode
      charged to various potentials in the range between -0.1 to -1.5 V.

PMID- 8286060
TI  - Theoretical design of a bis-orthopepetide derivative of a tetracationic porphyrin
      targeted toward a six-base pair sequence of DNA.
AB  - Tetra-(4-N-methylpyridyl)-porphyrin, (T4MPyP), is a tetracationic porphyrin that
      binds to G-C sequences of DNA by means of an intercalative mode. In order to
      extend its selective sequence recognition capacity for bases beyond the
      intercalation site, and in the major groove, we have undertaken the theoretical
      design of bis-ortho peptide derivatives of T4MPyP. In these, two ortho N
      methylpiperidinium nitrogens are linked to a cationic residue, L-Lys, L-Orn, or L
      Arg. The binding energetics of these novel compounds were compared for six
      distinct double-stranded palindromic hexanucleotide sequences. Four distinct
      modes of binding were compared: a) major, b) minor groove binding of both
      peptidic arms; c) a straddling mode in which each arm is in a different groove of
      DNA; d) exclusive binding of the arms to the sugar-phosphate backbone. For our
      most promising compound, that with Lys side-chains, a distinctive energetical
      advantage was computed in favor of an all-major groove binding to sequence
      d(CCCGGG)2. The corresponding complex is separated by an energy gap of 12
      kcal/mol, with respect to the second-best sequence bound in the major groove,
      d(GGCGCC)2, and of 20 kcal/mol with respect to minor groove binding to sequence
      d(TACGTA)2. The results obtained with such a prototypic compound indicate that it
      is fully possible to design sequence selective (> 6 base-pairs) photosensitizers
      as peptide derivatives of T4MPyP and prompt the engineering of further, more
      complex analogs thereof.

PMID- 8286061
TI  - Solution structure of the V3 loop of a Thailand HIV isolate.
AB  - The principal neutralizing determinant (PND) of human immunodeficiency virus
      (HIV) is located inside the third variable loop (designated the V3 loop) of the
      envelope glycoprotein gp120. The V3 loop is typically 35 amino-acids long, and
      the 1st and the 35th residues in the loop are invariant cystines involved in a
      disulfide-bridge. Although PNDs from different HIV isolates contain a conserved
      GPG-sequence, the amino acids flanking the conserved sequence show
      hypervariability among HIV isolates; the GPG and the two flanking regions are
      collectively referred to as the GPG-crest or the PND. The amino acid sequence
      variability in the GPG-crest gives rise to different antigenic specificities for
      different PNDs from different HIV isolates. By combining two-dimensional nuclear
      magnetic resonance (2D NMR) and molecular modeling techniques, we have developed
      a method to study (1) the global tertiary fold of the V3 loops of HIV and (2) the
      local structure of the PND at the tip of the V3 loop. In this article, we report
      the results of our structural studies on the V3 loop of a Thailand HIV isolate.
      The sequential assignment is made by combining DQF-COSY, TOCSY, and NOESY/ROESY
      experiments. Various intra- and inter-residue inter-proton distances are
      estimated by full-matrix analyses of the NOESY data at 100 and 400 ms of mixing
      times and of the ROESY data at 60 and 200 ms of mixing times. 100 inter-residue
      distances are used as structural constraints in a simulated annealing procedure
      to derive energetically stable structures. Two functional motifs in the V3 loop,
      i.e., the glycosylation site and the GPG-crest, form defined structures: a turn
      is located at the glycosylation site, and the GPG-crest forms a protruding domain
      with a type-II GPGQ turn. The other regions of the V3 loop are rather flexible-
      especially the C-terminal DIRKAYC-stretch. These flexible regions of the V3 loop
      lead to conformational flexure of the entire V3 loop without altering the local
      structures of the glycosylation site or the GPG-crest. However, the ROESY
      experiments revealed no slow exchange among different V3 loop conformations, and
      therefore the flexible conformations are in fast exchange within the NMR time
      scale. The extent of this conformational flexibility is also discussed.

PMID- 8286062
TI  - Spatial, sequence-order-independent structural comparison of alpha/beta proteins:
      evolutionary implications.
AB  - We present a unique sequence-order independent approach which allows examination
      of three dimensional structures, searching for spatially similar substructural
      motifs. If the amino acids composing the motifs are contiguous in the primary
      chain, that is, they follow each other in the sequence, a common ancestor and a
      divergent evolutionary process may be implied. On the other hand, if the three
      dimensional substructural motif consists of amino acids whose positions in the
      sequences vary between the different proteins, a convergent evolution might have
      taken place. Starting from different, ancient sequences, mutations may have
      occurred that brought about formation and conservation of a truly structural
      motif. Such a motif might be particularly suitable for fulfilling a specific
      function. Clearly, in order to be able to carry out such a task one needs a
      technique which allows comparisons of protein structures absolutely independent
      of their amino acid sequence-order. Our novel, efficient, computer vision based
      technique treats atoms (residues) as unconnected points in space, using strictly
      the atomic (either all atoms or only the C alpha atoms) coordinates. The order of
      the residues is completely disregarded. Detection, cataloging and analysis of
      "real" three-dimensional, sequence-order independent motifs in the
      crystallographic database is expected to be an invaluable tool for protein
      folding. Here we demonstrate the power of the technique by applying it to
      alpha/beta proteins. Our studies indicate that for some of the proteins, the
      "classical" structural alignments (conserving the amino acid order) are the
      optimal ones. Nevertheless, for others, truly spatial (out of sequential-order)
      amino acid equivalencing results in a better geometrical match.

PMID- 8286063
TI  - Conformational stability of the DNA-binding histone-like protein, HBsu, from
      Bacillus subtilis, and of the four HBsu variants [F29W], [F47W], [F50W] and
      [F79W].
AB  - From denaturation studies with urea a free energy delta GuH2O of unfolding of
      49.8 kJ.mol-1 at 25C was calculated for the histone-like DNA-binding protein HBsu
      from Bacillus subtilis. Unfolding was monitored by circular dichroism
      measurements observing the changes of the molar mean residue ellipticity [theta]
      at 222 nm. For the calculation of delta Gu a two-state model of unfolding, i.e.
      the unfolding of native dimers into unfolded monomers, was applied. The validity
      of this model in high ionic strength buffer was proven by measurements at
      different protein concentrations yielding the same delta Gu values. Four HBsu
      variants, each carrying one single point mutation ([F29W], [F47W], [F50W] and
      [F79W]) were analysed with respect to their stability against unfolding at
      increasing temperatures and urea concentrations. The delta Gu values of mutants
      were calculated using the two-state model and show a reduced stability of the
      variants [F29W], [F47W], [F50W] and [F79W] in comparison to the wild type HBsu
      with delta delta Gu values of -9.2 kJ.mol-1, -7.5 kJ.mol-1, -5.9 kJ.mol-1, and 
      7.5 kJ.mol-1, respectively. Similar delta delta Gu values were obtained for the
      HBsu mutant proteins by thermal unfolding experiments.

PMID- 8286064
TI  - Computer modelling studies of ribonuclease A-pyrimidine nucleotide complexes.
AB  - Different modes of binding of pyrimidine monophosphates 2'-UMP, 3'-UMP, 2'-CMP
      and 3'-CMP to ribonuclease (RNase) A are studied by energy minimization in
      torsion angle and subsequently in Cartesian coordinate space. The results are
      analysed in the light of primary binding sites. The hydrogen bonding pattern
      brings out roles for amino acids such as Asn44 and Ser123 apart from the well
      known active site residues viz., His12,Lys41,Thr45 and His119. Amino acid
      segments 43-45 and 119-121 seem to be guiding the ligand binding by forming a
      pocket. Many of the active site charged residues display considerable movement
      upon nucleotide binding.

PMID- 8286065
TI  - Conformation of polyene antibiotic, filipin III: CD and 1H NMR studies.
AB  - Detailed studies on the solution conformation of polyene antibiotic, filipin III
      using circular dichroism (CD) and proton nuclear magnetic resonance techniques
      have been carried out. In dimethyl sulfoxide (DMSO), filipin III exhibits
      concentration dependent aggregation-monomeric at lower and oligomeric at higher
      concentrations of the antibiotic. At concentrations used for 1H NMR studies (6 x
      10(-3)M) the molecule coexists as monomeric and oligomeric species. However,
      titration experiments indicated that, in a mixed solvent system of DMSO:methanol
      (2:3 v/v) the antibiotic exists only as a monomer. Complete 1H NMR assignments
      and the conformation of the monomer filipin III have been determined by the
      combined use of DQFCOSY and ROESY experiments in DMSO:methanol solvent system.

PMID- 8286066
TI  - Effects of different continium dielectric models in a molecular dynamics and
      energy minimization study of the antigenic loop of foot-and-mouth disease virus.
AB  - This study presents the influence of the dielectric constant on the final
      structure of the major antigenic loop of the FMDV serotype C. Minimizations have
      been performed on the nine-residue peptide Ac-TASARGDLA-NHMe, using two
      expressions for the dielectric constant: a distance-independent (epsilon =
      kappa), and a distance-dependent (epsilon = kappa *r) forms, and for kappa values
      from 1 to 10. In addition, kappa = 40 and 80 has also been considered for the
      constant expression of the dielectrics. The calculations suggest, for both
      expressions of the dielectrics, that for the sequence under study a value of
      kappa in the range of 2-6 performs an adequate treatment of the electrostatic
      interactions. Finally, molecular dynamic simulations at 298 K calculated with an
      effective dielectric constants of epsilon = 1*r and epsilon = 4*r are compared.
      The results indicated that a dielectric of epsilon = 4*r provides a peptide
      fluctuations which are in agreement with recent X-ray diffraction studies.

PMID- 8286067
TI  - Confronting the HIV epidemic in Asia and the Pacific: developing successful
      strategies to minimize the spread of HIV infection.

PMID- 8286068
TI  - Penetration of zidovudine into the cerebrospinal fluid of patients infected with
      HIV.
AB  - OBJECTIVE: To investigate penetration of zidovudine (ZDV) into the cerebrospinal
      fluid (CSF) of HIV-infected patients for whom a lumbar puncture was indicated.
      DESIGN: A prospective study. SETTING: General 525-bed hospital with special
      funding for treatment and research of HIV-infected patients. PATIENTS,
      PARTICIPANTS: Thirty-nine patients with a medical indication for lumbar puncture
      who used ZDV chronically were included in this study (50 samples in total). MAIN
      OUTCOME MEASURE: Determination of ZDV and proteins in CSF and plasma samples.
      RESULTS: CSF concentrations of ZDV showed little fluctuation 1-8 h after the last
      ingestion of ZDV. In contrast, plasma levels displayed large variability in this
      period and decreased exponentially over time. As a result, the CSF/plasma ratio
      increased linearly over time. No significant relation between the ZDV dose,
      neither the medical indication for lumbar puncture nor the protein ratio (as a
      measure for the integrity of the blood-brain barrier), and CSF levels of ZDV was
      found. The CSF/plasma ratio of ZDV did not give essential information on drug
      distribution into CSF. CONCLUSIONS: Penetration of ZDV into the CSF appears to be
      independent of the dose (range, 200-1250 mg daily), which may be an explanation
      for the efficacy of low doses of ZDV in the prevention and treatment of HIV
      related neurological diseases. ZDV levels were at steady-state during the first 6
      h after ingestion. The CSF/plasma ratio of ZDV concentrations is not an
      appropriate marker for drug penetration into CSF.

PMID- 8286069
TI  - Selective thymocyte depletion in neonatal HIV-1 thymic infection.
AB  - OBJECTIVE: To determine the impact of HIV-1 infection on thymocyte development,
      and the role of thymic infection on the pathogenesis of neonatal HIV-1 infection.
      DESIGN AND METHODS: The consequences of thymic infection by HIV-1 were examined
      by comparative histologic and molecular analyses of an asymptomatic, HIV-1
      seropositive 3-day-old subject, versus age- and treatment-matched controls. The
      presence of replicating virus was established by in situ hybridization with
      specific molecular probes to HIV-1. The distribution of thymocyte subsets was
      determined by quantitative flow cytometry following staining with antibodies to
      CD4 and CD8 cell surface proteins. RESULTS: The results show clear evidence of
      severe thymic involution, HIV-1 infection of thymocytes, and selective depletion
      of thymocyte subpopulations. The consequences of HIV-1 infection were a marked
      depletion of CD3+CD4+ CD8hi and CD3+CD4+CD8- cells. The phenotype of the residual
      thymic lymphoid population was predominantly that of immature CD3-CD4-CD8- double
      negative and CD3+CD4+CD8lo cells. CONCLUSION: Changes in the distribution of
      thymocyte subsets suggests a role for thymic involvement in the pathogenesis of
      HIV-1 infection in neonates.

PMID- 8286070
TI  - Change in neuropsychological performance in asymptomatic HIV infection: 1-year
      follow-up.
AB  - OBJECTIVE: To examine the stability of cognitive function in patients with
      asymptomatic HIV infection. DESIGN: Previous longitudinal studies of cognitive
      function have focused on patients who progress in terms of disease stage. The
      present study avoided this potential confounding factor by including only
      subjects who remained in the asymptomatic stage of infection over the follow-up
      period. METHOD: Subjects were administered an extensive neuropsychological test
      battery at baseline and 1 year follow-up. Overall performance was characterized
      as normal or abnormal based on the performance of a well-matched HIV-negative
      control group. RESULTS: A significantly higher proportion of HIV-positive
      subjects became abnormal at the follow-up examination. Comparison of the
      seropositive subjects who remained normal with those who became abnormal revealed
      no differences at baseline on age, education, depression or CD4 levels. Subjects
      who became abnormal had worse performance at baseline on measures of information
      processing, verbal learning and memory, and reaction time. CONCLUSIONS: These
      data indicate that cognitive function may decline in some patients who continue
      to be in the asymptomatic stage of infection. Patients with a pattern of
      cognitive abnormalities at baseline, which includes information processing and
      reaction time deficits, may be at increased risk for declines in function during
      early stages of infection.

PMID- 8286071
TI  - Risk factors for HIV infection among abandoned Romanian children.
AB  - OBJECTIVE: To determine risk factors for HIV infection among abandoned Romanian
      infants and children living in a public institution. METHODS: A cross-sectional
      study was conducted in June 1990 among 101 children between 0 and 4 years of age
      living in an orphanage. Orphanage and hospital records were reviewed and a blood
      specimen for hepatitis B and HIV serologic testing obtained from each child. A
      case-control study was conducted using data from the cross-sectional study. Cases
      were HIV-positive children; one HIV-negative control, matched by age, was
      selected for each case. RESULTS: Overall, 20 (20%) children were HIV-positive, 88
      (87%) tested positive for antibody to hepatitis B core antigen, and 32 (32%) were
      hepatitis B surface antigen-positive. In the case-control study, HIV-positive
      children had received more therapeutic injections [mean, 280; median, 231] than
      age-matched HIV-negative children [mean; 142, median, 155; P = 0.02]. Cases were
      more likely than controls to have received over 200 lifetime injections (odds
      ratio, 5.7; 95% confidence interval, 1.2-32.7). Blood transfusions and mother-to
      child transmission were excluded as routes of HIV transmission. By reviewing
      sterilization records and interviewing local health-care workers, we determined
      that needles and syringes were often re-used without proper disinfection in the
      orphanage. CONCLUSIONS: These data provide strong epidemiologic evidence that
      indiscriminate injections with contaminated needles and syringes were responsible
      for HIV transmission in this population.

PMID- 8286072
TI  - Evaluation of HIV testing in Sweden, 1985-1991.
AB  - OBJECTIVE: Evaluation of the extent and outcome of HIV testing in Sweden. DESIGN:
      Data from screening programmes, laboratory and clinical reports were compared and
      a national survey on HIV testing was performed. RESULTS: The proportion found to
      be positive in screening of blood donors, pregnant women and sexually transmitted
      disease patients were approximately 1/100,000, 1/10,000 and 1-2/1000,
      respectively. One-quarter of the men and one-third of the women in Sweden aged 16
      74 years reported that they had been tested for HIV at least once. CONCLUSION:
      There is a high cost involved in detecting HIV-infected individuals through
      general testing. This cost can be justified if we believe that awareness of an
      infection substantially reduces the risk of further transmission.

PMID- 8286073
TI  - Impact of HIV counseling and testing among child-bearing women in Kinshasa,
      Zaire.
AB  - OBJECTIVE: To determine the impact of HIV counseling and testing among child
      bearing women. STUDY SETTING: Mama Yemo Hospital in Kinshasa, Zaire. PARTICIPANTS
      AND INTERVENTIONS: After informed consent, 187 HIV-seropositive and 177 HIV
      seronegative child-bearing women received pre- and post-test counseling for HIV
      infection. MAIN OUTCOME MEASURES: Participant knowledge of HIV/AIDS and plans for
      notifying partners of serologic status and contraceptive use at the time of
      counseling, and actual partner involvement and contraception use 12 months later.
      RESULTS: During pre-test counseling, participant knowledge of HIV infection was
      high, although 30% of women were unaware of perinatal HIV transmission, and 50%
      did not know that HIV infection could be asymptomatic. At post-test counseling,
      70% of mothers (47% of HIV-seropositive, 94% of HIV-seronegative) intended to
      notify their partners and have joint counseling and testing, although after 12
      months, only 2.2% of all women and 7.9% of those who desired assistance to notify
      their partner returned with their partners for joint counseling and testing.
      Similarly, 86% planned to use birth control (61% condoms), with HIV-seropositive
      women more likely to prefer condoms than HIV-seronegative women (71 versus 53%; P
      < 0.001). After 12-months, however, only 20% of HIV-seropositive women reported
      condom use, and the frequency of pregnancy in both groups was approximately
      equal. CONCLUSIONS: HIV counseling and testing led to higher rates of
      contraceptive and condom use, although the actual level was lower than the
      intended use. To further reduce the risk of heterosexual and perinatal HIV
      transmission in families with an HIV-infected woman, counseling should also
      include their male partners.

PMID- 8286074
TI  - Multiple sexual partners and mother-to-child transmission of HIV-1.
AB  - OBJECTIVE: To investigate risk factors for mother-to-child transmission of HIV-1,
      particularly sexual behavior before and during pregnancy. DESIGN AND METHODS:
      This study is part of a prospective cohort study in Butare, Rwanda, of 318 HIV-1
      seropositive and 309 HIV-1-seronegative women enrolled during pregnancy and
      followed for a mean duration of 21 months (range, 8-34 months). Clinical follow
      up of the mother-infant pairs was performed at 6-week intervals during the first
      year of life and at 4-month intervals thereafter. Detailed sexual history
      interviews were conducted during pregnancy and at the first postnatal visit.
      RESULTS: Of 184 singleton infants born to HIV-1-infected mothers who survived the
      neonatal period, 32 (17%) children were classified as HIV-1-infected, 130 (71%)
      as not infected, and 22 (12%) died with indeterminate HIV-1 infection status. The
      vertical transmission rate was estimated to be between 20 and 29%. Unprotected
      sexual intercourse with increased number of partners during the past 5 years was
      strongly associated with mother-to-child transmission (P < 0.001), even after
      adjustment for maternal CD4/CD8 ratio, parity, history of sexually transmitted
      diseases, and evidence of genital infection during pregnancy. In a multivariate
      analysis, excluding children with indeterminate HIV-1 status, odds ratios for
      vertical transmission were 2.6 [95% confidence interval (CI), 1.0-6.9] for
      maternal CD4/CD8 ratio < 0.5 and 3.6 (95% CI, 1.1-11.8) for more than three
      sexual partners versus a single partner. Women with more than one sexual partner
      during the first trimester of pregnancy were at particularly high risk of
      transmitting the virus. CONCLUSION: Unprotected sexual intercourse with multiple
      partners before and during pregnancy in a population with high HIV-1
      seroprevalence may well increase the likelihood of HIV-1 transmission from an
      infected mother to her child.

PMID- 8286076
TI  - Syringe-mediated drug-sharing (backloading): a new risk factor for HIV among
      injecting drug users.
AB  - BACKGROUND: In syringe-mediated drug-sharing (backloading), injecting drug users
      (IDU) use their syringes to mix drugs and to give measured shares to other IDU by
      squirting drug solution into the syringes of other IDU. Backloading has been
      discussed as a potential HIV risk factor, but its role as an HIV transmission
      route has not been established empirically. METHODS: Six hundred and sixty IDU
      who had injected drugs in the previous 2 years were street-recruited from
      Bushwick, New York City through chain referral, tested for HIV antibody and
      interviewed about sexual and drug-risk behaviors. RESULTS: Receiving drugs via
      backloading in the previous 2 years was reported by 24.5% of the subjects. These
      subjects had significantly higher HIV seroprevalence than those who did not
      receive drugs by backloading (odds ratio, 2.2; 95% confidence interval, 1.5-3.1).
      Backloading remained positively and significantly associated with HIV
      seropositivity in stepwise logistic regression, and in a series of simultaneous
      logistic models controlling for sociodemographic variables and for sexual and
      drug risk variables. CONCLUSIONS: Backloading can be a route of HIV transmission
      among IDU and should be incorporated into risk-factor studies and HIV
      transmission modeling. Many IDU who avoid other high-risk drug-injection
      practices may overlook the risk of backloading. HIV prevention programs should
      warn IDU against syringe-mediated drug-sharing and work together to develop ways
      to avoid it.

PMID- 8286075
TI  - Behavioral and sociodemographic risks for frequent visits to commercial sex
      workers among northern Thai men.
AB  - OBJECTIVE: The transmission of HIV-1 in Thailand has recently been attributed to
      exposure to infected commercial sex workers (CSW). We sought to identify risk
      factors for patterns of CSW visits among northern Thai men. DESIGN: Retrospective
      recall of lifetime and recent CSW visits and associated risk factors were
      obtained by interview. SETTING: Two military bases in northern Thailand.
      PARTICIPANTS: We enrolled two cohorts (n = 2417) of young men, aged 19-23 years,
      who were conscripted into the Royal Thai Army and Air Force from six provinces in
      northern Thailand in May and November 1991. MAIN OUTCOME MEASURES: Frequency of
      self-reported lifetime and recent sex with CSW. RESULTS: Multivariate results
      showed that lower socioeconomic status, early first intercourse and substance-use
      factors (alcohol, marijuana, other drugs, and smoking) associated with lifetime
      and recent sex with CSW. Sexual intercourse with other female partners, lower
      price paid at last CSW visit and frequency of condom use with CSW did not
      differentiate frequent from infrequent CSW visitors. CONCLUSIONS: Limits in the
      frequency of sex with CSW, improved condom practices and reduction of drinking
      prior to CSW visits would all appear to provide substantial protection from
      exposure to HIV-1 in this setting.

PMID- 8286077
TI  - AIDS surveillance: a direct assessment of under-reporting.
AB  - OBJECTIVE: To assess directly the extent of under-reporting of AIDS cases to the
      National AIDS surveillance system. DESIGN: All AIDS cases diagnosed from 1
      January 1982 to 1 August 1989 in Riverside Health Authority were identified from
      a local register of HIV infection and cross-checked against records of AIDS cases
      reported to the national AIDS surveillance system. SETTING: Riverside Health
      Authority, London, UK. MAIN OUTCOME MEASURES: An estimate of under-reporting was
      made by identifying both the number of AIDS cases that had not been reported and
      the number of AIDS cases reported after August 1989 (allowing for reporting
      delay). Changes in the timeliness, 1982-1989, of AIDS reporting by Riverside
      physicians were measured by comparing reporting delay (time between diagnosis and
      report) and the proportion of AIDS cases reported more than a year after
      diagnosis (non-reports). RESULTS: A total of 807 AIDS cases were identified.
      Under-reporting of AIDS cases was found to be 10%; less than 3% (20 cases) of the
      AIDS identified had not been reported by September 1991. The timeliness of AIDS
      reporting from Riverside improved significantly from 1987, when the median
      reporting delay fell from 7 to 4 months, and the proportion of non-reports fell
      from 36 to 17% (Mann-Whitney U test P < 0.001, chi 2 test P < 0.001,
      respectively). CONCLUSIONS: Our estimate of 10% AIDS under-reporting is half that
      used to adjust the previous forecasts of the AIDS epidemic in the UK, confirms
      current thinking that under-reporting lies between 5 and 15%, and supports the
      view that AIDS reporting is more complete than the reporting of most other
      infectious diseases.

PMID- 8286078
TI  - Kaposi's sarcoma as a sexually transmissible infection: an analysis of Australian
      AIDS surveillance data. The National HIV Surveillance Committee.
AB  - OBJECTIVE: To further examine the hypothesis that Kaposi's sarcoma (KS) among
      people with AIDS is caused by a sexually transmissible infectious agent. DESIGN:
      Analysis of Australian AIDS surveillance data for the period 1982-1991 by sex,
      age, exposure category, country of birth, year and place of diagnosis. MAIN
      OUTCOME MEASURES: Percentage of people with AIDS who had KS. RESULTS: In
      Australia, by November 1991, 17.2% (527 out of 3067) of individuals with AIDS
      aged > or = 13 years had presented with KS as their AIDS-defining illness: men,
      17.6% (524 out of 2977); women, 3.4% (three out of 87) (P < 0.001). KS was
      predominantly reported in people aged 20-49 years and there were no cases in
      children < 13 years of age. In general, KS was more common in those who had
      acquired HIV by sexual contact rather than parenterally. Among people aged > or =
      13 years, the proportion with KS ranged from 0.0% (none out of 41) in men with
      haemophilia to 1 Iford 9.0% (483 out of 2542) in men reporting homosexual
      contact. Between 1984-1985 and 1990-1991, the percentage of men with AIDS
      reporting homosexual contact who presented with KS declined from 30% (37 out of
      124) to 15% (145 out of 995) (chi 2 for a linear trend, P < 0.001). For men with
      AIDS reporting homosexual contact, the percentage with KS in New South Wales and
      Victoria (20.3%) was higher than in the other States and Territories (12.5%) (P <
      0.001). New South Wales and Victoria have also reported the highest incidence of
      AIDS in Australia. CONCLUSION: The epidemiological characteristics of KS among
      people with AIDS in Australia are broadly consistent with those reported from the
      United States and Europe. This provides further evidence that KS may be caused by
      a sexually transmissible infectious agent. The nature of the infectious agent and
      its mode of transmission have yet to be determined.

PMID- 8286079
TI  - Viral phenotype and severity of HIV-1 infection: are children different from
      adults?

PMID- 8286080
TI  - HIV-related morbidity and mortality in sub-Saharan Africa: opportunities for
      prevention.

PMID- 8286082
TI  - HIV seropositivity of blood donations in Spain from 1988 to 1992. The HIV Blood
      Donation Study Group.

PMID- 8286081
TI  - Do needle exchanges help to control the spread of HIV among injecting drug users?

PMID- 8286083
TI  - Polymerase chain reaction procedure for rapid diagnosis of HIV infection.

PMID- 8286084
TI  - Screening of HIV-1 proviral DNA using simple protocol polymerase chain reaction
      in Thai blood donors.

PMID- 8286085
TI  - Specific tolerance to HIV-1 antigens in an infant with rapid progression to AIDS.

PMID- 8286086
TI  - Transmission of zidovudine-resistant HIV-1.

PMID- 8286087
TI  - Successful treatment of disseminated cryptococcosis with high-dose oral
      fluconazole.

PMID- 8286088
TI  - The effect of Pneumocystis carinii pneumonia prophylaxis regimens on the
      incidence of bacterial infections in HIV-infected patients.

PMID- 8286089
TI  - Statistics from the Centers for Disease Control and Prevention.

PMID- 8286090
TI  - Acinetobacter in Denmark: I. Taxonomy, antibiotic susceptibility, and
      pathogenicity of 112 clinical strains.
AB  - One hundred and twelve clinical strains of Acinetobacter were collected during a
      7-month period in 1990-1991 from Danish clinical microbiology departments.
      According to the old notation, 37 strains were biovar anitratus and 75 b.lwoffii.
      Using the newest terminology, 35 strains were unambiguously identified as the
      species A. haemolyticus, A. johnsonii, A. radioresistens, and as the unnamed
      phenons 6, 10, and 14, by a numerical approach using a simplified phenotypical
      identification scheme. Most of the remaining strains were identified to the
      genotypically heterogeneous A. calcoaceticus-A. baumannii complex and the A.
      lwoffii phenotype. Sixteen strains (14%) were left unidentified. Eight A. lwoffii
      strains were glucose-oxidizing and were thus classified as b. anitratus using the
      old terminology. The strains were tested for susceptibility to ampicillin,
      piperacillin, ticarcillin, cefotaxime, ceftazidime, imipenem, gentamicin,
      tetracycline, sulphonamide, and nalidixic acid. All strains were susceptible to
      imipenem. The susceptibility to the remaining beta-lactams was variable, the A.
      lwoffii isolates being the most and the A. calcoaceticus-A. baumannii complex
      strains the least susceptible. All non-A. calcoaceticus-A. baumannii complex
      strains were susceptible to all other antibiotics tested, except for one A.
      lwoffii strain that was sulphonamide resistant. Twenty-two percent of the strains
      in the A. calcoaceticus-A. baumannii complex showed reduced susceptibility or
      resistance to gentamicin, but only sporadic resistance to sulphonamides,
      tetracyclines, and nalidixic acid. Eight infections were recorded: three cases of
      septicaemia, three cases of peritonitis related to continuous ambulatory
      peritoneal dialysis, and two cases of recurrent urinary tract infection. No
      epidemics were detected.

PMID- 8286091
TI  - Acinetobacter in Denmark: II. Molecular studies of the Acinetobacter
      calcoaceticus-Acinetobacter baumannii complex.
AB  - The Acinetobacter calcoaceticus-Acinetobacter baumannii complex consists of four
      closely related "genospecies" or DNA groups: DNA group 1 (A. calcoaceticus), DNA
      group 2 (A. baumannii), DNA 3, and Tjernberg & Ursing's DNA group 13. Strains in
      this complex are so similar phenotypically that it is often impossible to
      identify them to the DNA group level by the use of biochemical tests. Twenty
      three Danish clinical strains from 23 patients phenotypically identified to the
      A. calcoaceticus-A. baumannii complex were studied by ribotyping, plasmid
      profiling, and DNA/DNA hybridization. Multiple isolates were recovered from four
      patients. These were identical in each patient as judged by phenotype, ribotype
      and plasmic profile. Seventeen different ribotypes were observed among the 23
      strains, and by using this method 19 out of the 23 strains could be identified to
      the DNA group level. Five strains were allocated to DNA group 2 (A. baumannii),
      eight to DNA group 3, and six to DNA group 13. These findings were confirmed by
      DNA/DNA hybridization. Two of the four unidentified strains were genotypically
      most closely related to but different from DNA groups 1 and 3. The last two
      strains were most closely related to DNA group 13. These four strains represent
      two new DNA groups within the A. calcoaceticus-A. baumannii-complex. One to four
      plasmids in the size range 2.1 kb- > kb were detected in 13 of the strains. Nine
      plasmid profiles were seen, indicating the usefulness of this typing method if
      the strains contain plasmids. The study also indicates that ribotyping is useful
      both for typing and for identification purposes, and that the genetic
      relationship in this area are more diverse than hitherto perceived. Taxonomic
      reconsiderations are warranted.

PMID- 8286092
TI  - Melanocytic lesions in a private pathology practice. Comparison of histologic
      features in different tumor types with particular reference to dysplastic nevi.
AB  - This study reviews a total of 1000 melanocytic lesions--two separate 500
      consecutive sample groupings from 1980 and 1989, respectively--diagnosed in a
      private non-hospital-associated pathology practice. Lesions were classified as
      lentigo simplex, congenital nevus, "common" nevus, dysplastic nevus, blue nevus,
      Spitz's nevus or malignant melanoma. A comparison of the two periods reveals an
      increase in dysplastic nevi from one in 1980 to nine in 1989. The histologic
      changes in these nevi were compared to those of the other tumors. Pronounced
      cytologic atypia was seen in the melanocytes of a few "common" nevi, but more
      often in the dysplastic nevi and in all of the melanomas. Slight nuclear atypia
      was usual in "common" nevi and lentigines, and also fibroplasia, lymphocytic
      infiltration, vessel proliferation and pigment incontinence were seen in both
      "common" nevi and dysplastic nevi. It is concluded that no single histologic
      variable was specific for dysplastic nevi.

PMID- 8286093
TI  - Characterization of glycoproteins from Chlamydia trachomatis using lectins.
AB  - Glycoproteins in Chlamydia trachomatis, serotype L1, elementary bodies were
      studied by lectin blotting. A panel of 23 lectins representing a variety of sugar
      specificities was used. The pattern of lectin-binding specificities at a peptide
      band was studied in order to determine the type and structure of its
      glycoconjugate. To establish chlamydial origin of the glycopeptide bands in the
      blot, control samples from non-infected host cell membranes were run in parallel.
      Terminal mannosidic structures were demonstrated in a 72 kDa glycopeptide (gp72)
      by its selective binding of Galanthus nivalis lectin (GNA). Sialic acids were
      found in two chlamydial glycopeptides, gp40 and gp64, which appear to carry O
      linked glycoconjugates as they bound the peanut agglutinin (PNA, both gp40 and
      gp64) and jackfruit lectin (Jac, only gp40). Such structures were also present in
      other chlamydial glycopeptides. Lectins with specificities for fucose in
      different links, galactose and N-acetyl glucosamine bound to several chlamydial
      peptides. On the basis of our results we suggest an alternative mechanism for
      uptake of chlamydial elementary bodies into host cells, namely phagocytosis
      mediated by eukaryotic cell surface lectins.

PMID- 8286094
TI  - Human intestinal spirochaetosis in mid-Norway. A retrospective histopathological
      study with clinical correlations.
AB  - Among 1205 mid-Norwegian patients who underwent colorectal biopsies during 1990,
      30 cases (2.5%) with human intestinal spirochaetosis (HIS) were found. In only
      two cases were the spirochaetes mentioned in the biopsy reports. Cases with HIS
      showed a 7:3 male preponderance, but the mean age did not differ from that in the
      whole material. The spirochaetes were slightly more frequent in the rectum than
      in other parts of the large bowel. There was no indication of seasonal or
      geographical clustering of HIS and no association with occupation, use of certain
      drugs or underlying diseases. Most cases had HIS as the only positive biopsy
      finding, but the condition was also seen in connection with adenocarcinomas,
      Crohn's disease, and metaplastic and granulation polyps. The predominant symptoms
      of patients with HIS were faecal blood, diarrhoea, abdominal pain and
      constipation.

PMID- 8286095
TI  - Xanthogranulomatous cholecystitis. A clinicopathological study of 20 cases and
      review of the literature.
AB  - Xanthogranulomatous cholecystitis (XGC) is a focal or diffuse destructive
      inflammatory process of the gall bladder, characterized macroscopically by
      yellowish tumour-like masses in the wall of the gall bladder. Microscopically, it
      is characterized in the early stages by a large number of foamy histiocytes and
      acute inflammatory cells. Later stages demonstrate increasing fibrosis. The gall
      bladder from 20 of 352 consecutive patients subjected to cholecystectomy showed
      XGC. Gall stones were found in the gall bladder of all 20 patients and in the
      ductus choledochus in 3 cases. Perforation of the gall bladder was observed at
      operation in six cases; in one case there was also a fistula to the colon. A
      perivesical abscess was found in five other cases. Adhesions to the surrounding
      structures were seen in a total of 16 cases. Pathogenetically, XGC is probably
      due to an interplay between obstruction of the gall flow, infection with
      subsequent inflammation, and leakage of gall fluid to the tissue, where
      histiocytes accumulate and phagocytize the bile pigment, haemosiderin and
      cholesterol, resulting in the formation of xanthoma cells. The correct diagnosis
      of XGC is important for several reasons, first and foremost due to the high
      frequency of complications, but not least because the condition may give rise
      peroperatively to the suspicion of malignancy. The new laparoscopic method for
      cholecystectomies further stresses the necessity of correct preoperative
      diagnosis of complicating disease.

PMID- 8286096
TI  - Search for Mycobacterium paratuberculosis DNA in tissue from patients with
      sarcoidosis by enzymatic gene amplification.
AB  - The etiology of sarcoidosis has not yet been established, but several
      mycobacterial species have been implicated in the pathogenesis of this disease.
      We have used a nested primer polymerase chain reaction (PCR) specific for the
      IS900 Mycobacterium paratuberculosis insertion element to analyse paraffin
      embedded mediastinal lymphoid tissue from 18 patients with pulmonary sarcoidosis
      verified by mediastinoscopy. Only the positive control contained M.
      paratuberculosis-specific DNA. The present study does not support a role for M.
      paratuberculosis in the pathogenesis of sarcoidosis. However, further studies are
      needed in order to clarify the possible role of other mycobacteria in this
      disease.

PMID- 8286097
TI  - Induction of oxidative burst response in human neutrophils by immune complexes
      made in vitro of lipopolysaccharide and hyperimmune serum from chronically
      infected patients.
AB  - Purified lipopolysaccharide (LPS) from Pseudomonas aeruginosa was used as an
      antigen for immune complex (IC) formation in vitro together with hyperimmune sera
      from chronically P. aeruginosa-infected patients with cystic fibrosis (CF). P.
      aeruginosa LPS by itself did not induce an oxidative burst in human neutrophil
      granulocytes (PMN)s measured by chemiluminescence (CL). This was also the case
      using hyperimmune CF serum alone. In contrast, P. aeruginosa LPS together with CF
      serum did induce a CL response. The CL responses varied depending on the sera
      used for IC formation, and were reduced when protein A preabsorbed sera were
      used. PEG precipitation of the ICs from the mixture increased the CL response.
      These findings indicate that the CL responses induced by the mixture of P.
      aeruginosa LPS and CF serum were due to IC formation and an Fc-mediated
      stimulation of the PMNs. It is concluded that ICs made from sera of chronically
      infected CF patients and purified P. aeruginosa LPS are biologically active in
      terms of activating PMNs, and may contribute to the lung tissue damage seen in
      this group of patients.

PMID- 8286098
TI  - Management of penetrating wounds of the neck.
AB  - Management policies for penetrating wounds of the neck vary from mandatory
      surgical exploration to selective surgical exploration following extensive or
      minimal imaging investigation. In order to review the treatment protocol at Sheba
      Medical Center, Tel Hashomer, Israel, we retrospectively studied 21 patients who
      were treated between the years 1984 and 1989. Thirteen had gunshot injuries and
      eight had stab wounds. Eight patients had undergone immediate exploration of the
      neck. Four patients had died, but all of these latter patients had evidence for
      significant bleeding that could have been detected within a short time of
      admission. On the basis of our findings and previous studies, we conclude that:
      presenting features of neck injuries should be differentiated into two basic
      categories: immediately life-threatening and not immediately life-threatening.
      Immediately life-threatening features include overt massive bleeding, expanding
      hematoma, non-expanding hematoma in the presence of hemodynamic instability,
      hemomediastinum, hemothorax, and hypovolemic shock. In all of these cases,
      immediate surgical exploration is mandatory. Non-life-threatening features
      include any signs of vascular complication in a hemodynamically stable patient,
      signs of upper aerodigestive tract lesions (when initial treatment has already
      relieved respiratory distress) and peripheral neurological deficits. These
      patients should undergo thorough imaging investigations on the basis of which the
      need for and the nature of possible surgical intervention can be determined.

PMID- 8286099
TI  - Aerodynamic characteristics of the Provox low-resistance indwelling voice
      prosthesis.
AB  - The use of various prostheses for voice rehabilitation after total laryngectomy
      has become widely accepted in recent years. Two different types of prostheses can
      be distinguished: non-indwelling devices, which can be removed and replaced by
      the patient, and indwelling voice prostheses, which have to be removed and
      replaced by a physician. In this report we describe the in vitro measurement of
      the airflow dynamics of the recently developed Provox low-resistance, indwelling
      voice prosthesis. Airflows used in these experiments varied from 0.05 to 0.4 ls
      1. With increasing flows, the trans-device air pressure against airflow rates
      increased from 0.28 kPa to 1.36 kPa, while the mean airflow resistance decreased
      from 5.6 to 3.4 kPa l-1 s-1. From these data and by comparison with data for
      other prostheses, the Provox voice prosthesis shows favorable airflow
      characteristics.

PMID- 8286100
TI  - Malignant nerve sheath tumors of the head and neck: four case studies and review
      of the literature.
AB  - Malignant peripheral nerve sheath tumors (MPNST) are very uncommon neoplasms.
      While the incidence of these lesions is estimated to be 0.001% in a general
      population, they make up 5-15% of all soft tissue sarcomas in the head and neck
      region. We present four cases of MPNST in the head and neck. Since certain
      difficulties were encountered in diagnosis, the importance of clinical evaluation
      is emphasized. The prognosis for these tumor patients is poor in spite of
      improvements in diagnostic and therapeutic modalities.

PMID- 8286101
TI  - Symptoms and signs and their prognostic value in tracheal carcinoma.
AB  - Of all the 95 primary tracheal carcinomas diagnosed in Finland in 1967-1985, 72%
      were squamous cell carcinomas. Fifty-three percent were located in the lower
      third of the trachea. main symptoms were dyspnea, cough and hemoptysis. Fifty
      nine percent of the patients developed extratracheal growth during the follow-up
      of 12 years, with lungs, neck, liver, and bones being the most common sites. In
      addition, autopsy revealed mediastinal metastases in 25% of patients. Vocal cord
      palsy at the time of diagnosis was present in 33%. The size and location of tumor
      in the trachea did not affect survival significantly. Patients with adenoid
      cystic carcinomas had the best prognosis.

PMID- 8286102
TI  - Diagnostic and therapeutic management of atypical mycobacterial infections in
      children.
AB  - A series of 12 children (9 girls, 3 boys) with non-tuberculous mycobacterial
      lymphadenitis was reviewed to define the most frequent presenting features,
      helpful diagnostic measures and optimal management. The mean age at diagnosis was
      42 months and cervical nodes in the submandibular region were most commonly
      affected. In most of the children the diagnosis was made on the basis of a
      positive intradermal skin test with specific antigens for atypical mycobacteria.
      The diagnosis was confirmed in all but one case by histopathologic examination.
      Total excision of the affected gland was recommended as the therapy of choice in
      the patients treated.

PMID- 8286103
TI  - erbB-3, a third member of the erbB/epidermal growth factor receptor gene family:
      its expression in head and neck cancer cell lines.
AB  - Proto-oncogenes encoding growth factor receptors constitute several distinct
      families with close overall structural homology. The highest degree of homology
      can be observed in their catalytic domains, which are essential for intrinsic
      tyrosine kinase activity. Growth factor receptors in several of these families
      play critical roles in the regulation of normal cell growth and development. Some
      of these molecules have been implicated in the neoplastic process as well. A
      related DNA fragment distinct from epidermal growth factor receptor and erbB-2
      genes was detected by reduced stringency hybridization of v-erbB to normal
      genomic human DNA. The expression of erbB-3 was studied by southern and northern
      blot technique in a subset of nine head and neck tumor cell lines, as well as in
      three immortalized cultures established from normal human salivary glands. No
      gene amplification of erb-B-3 was noted in any of the head and neck cell lines.
      The 6.2 kb transcript of erbB-3 was elevated significantly in an epidermoid
      carcinoma of the larynx (A388) and an esophageal carcinoma (HA 114).

PMID- 8286104
TI  - Changes in cochlear oxygenation, microcirculation and auditory function during
      prolonged general hypoxia.
AB  - Changes in cochlear microcirculation and oxygenation and auditory function were
      examined in anesthetized guinea pigs during prolonged hypoxic ventilation (8%
      oxygen in nitrogen) for 1 h. Cochlear blood flow and perilymphatic oxygen partial
      pressure were measured using laser Doppler flowmetry and oxygen-sensitive
      microelectrodes. Auditory function was examined by recording cochlear
      microphonics, compound action potentials and auditory evoked brainstem response.
      Blood pressure and heart rate were monitored. During systemic hypoxia, the
      perilymphatic PO2 dropped on average to about 70% of the initial value. Cochlear
      and brainstem potentials showed a mean reduction to 75-82%. Different effects of
      hypoxia on cochlear blood flow were observed and included decreases as well as
      increases. Mean arterial blood pressure declined significantly during hypoxia,
      while the heart rate remained constant. The changed variables returned to normal
      during reventilation with room air. The findings are discussed with regard to
      their significance as an animal model for the study of hypoxia-induced cochlear
      pathophysiology.

PMID- 8286105
TI  - Electron and fluorescence microscopic investigations on composition and structure
      of the epithelial basement membrane of the human inferior nasal concha.
AB  - Light and electron microscopic as well as immunohistochemical investigations were
      performed on the basement membrane (BM) of the nasal mucosa from the inferior
      nasal conchae of 20 patients, aged 15-50 years. Two of the patients served as
      controls. Clinical disorders requiring the turbinectomies were hyperplastic nasal
      inferior conchae (17 patients) and immobile cilia syndrome (1 patient). In all
      cases light microscopy demonstrated a 10-15 microns thick homogeneous BM
      underneath an intact epithelium. Electron microscopic findings revealed a typical
      subepithelial basal lamina (BL). The remaining parts of the BM consisted of
      single, isolated 25-mm-thick collagenous fibrils. Only a few cells and small
      unmyelinated nerves occurred in this layer. Immunohistochemical investigations
      showed BL components (collagen type IV, laminin, nidogen and heparan sulfate
      proteoglycan) directly underneath the epithelium. Collagen types I, III, V, and
      VI could also be demonstrated immunohistochemically in the remaining parts of the
      BM. Collagen type VII was allocated to the anchor filaments beneath the BL. This
      special BM is presumed to contribute to mechanical stabilization of the
      epithelium. The significance of the BL and the subepithelial connective tissue
      for the behavior of the epithelium--e.g. direction of differentiation--are
      discussed.

PMID- 8286106
TI  - A trial of individual dose intensity and relative performance factors in tegafur
      maintenance chemotherapy for head and neck cancer.
AB  - Tegafur (Sunfural-S), as masked compound of a 5-fluorouracil derivative, was
      administered orally as a maintenance chemotherapeutic agent at a dose of 600
      mg/day in 98 cases of head and neck epithelial cancer. The effectiveness of the
      drug was evaluated by a statistical method involving two formulae: individual
      dose intensity (IDI) and relative performance (RP). When comparing patients rated
      above a reference IDI value of 1.0 with those rated below 1.0, it was not
      possible to predict patient survival or tumor-free rates. In contrast, the value
      of the RP did show such a correlation. These findings support the effectiveness
      of Tegafur as a maintenance chemotherapeutic treatment for head and neck cancer
      patients.

PMID- 8286107
TI  - Sugar-binding sites with specificity for glucosamine in the guinea pig middle ear
      mucosa.
AB  - Glucosamine-binding sites were detected in Lowicryl K4M-embedded guinea pig
      middle ear mucosa by electron microscopy, using glucosaminyl bovine serum
      albumin. Incubation of ultrathin tissue sections with gold-labeled glucosaminyl
      bovine serum albumin (GlcN/BSA/gold) resulted in binding mainly on cilia,
      microvilli, rough endoplasmic reticulum and nuclei. The sugar binding was not
      inhibited after ultrathin sections had been digested with trypsin or
      neuraminidase. Various carbohydrates and glycoconjugates were tested as
      competitive inhibitors of GlcN/BSA/gold labeling on the tissue sections. The
      sugar specificity range detected by the glucosamine-binding sites included
      glucosamine, N-acetylglucosamine, mannose and fucose, whereas N
      acetylgalactosamine, galactose and glucose were not detectable. A series of
      endotoxic substances such as Salmonella minnesota Re595 lipid A complex with BSA
      and lipopolysaccharides (LPS) derived from Escherichia coli 055:B5 or S.
      minnesota Re595 also competed with GlcN/BSA/gold binding. This indicates that the
      lipid A backbone glucosamine or other carbohydrate portions of LPS is a part of
      the structure recognized by glucosamine-binding sites.

PMID- 8286108
TI  - An electrocochleographic study of acute low-tone sensorineural hearing loss.
AB  - Twenty-four patients with acute low-tone sensorineural hearing loss (ALHL) were
      examined using electrocochleography. The negative summating potential (SP)
      amplitude and the summating potential/action potential (AP) ratio were
      significantly greater in the ALHL patients than in normals. The SP/AP ratio was
      smaller in the ALHL patients than in patients with known Meniere's disease and
      moderate hearing loss, although the SP amplitude was somewhat greater in the
      former. An abnormal increase in the SP amplitude following click stimuli was
      found in 54% of the ALHL patients, while the SP/AP ratio was increased abnormally
      in 63% of these patients. These findings suggest that the pathophysiology of ALHL
      may be similar to that for endolymphatic hydrops.

PMID- 8286109
TI  - Sex determination of in vitro developed buffalo (Bubalus bubalis) embryos by DNA
      amplification.
AB  - This study was conducted to determine the sex of buffalo embryos produced in
      vitro by amplifying male specific DNA sequences using the polymerase chain
      reaction (PCR). This method uses three different pairs of bovine Y-chromosome
      specific primers and a pair of bovine satellite specific primers. Buffalo in
      vitro fertilized embryos at the 4-cell to blastocyst stage were collected at days
      3, 4, 6, and 8 postinsemination, and the sex of each embryo was determined using
      all three different Y-chromosome specific primers. The bovine satellite sequence
      specific primers recognize similar sequences in buffalo and are amplified both in
      males and in females. Similarly, Y-chromosome specific primers amplify the
      similar Y-chromosome specific sequences in male embryos of buffalo. Upon
      examining genomic DNA from lymphocytes of adult males and females, and embryos,
      the results demonstrate the feasibility of embryo sexing in buffaloes.
      Furthermore, sex determination by PCR was found to be a rapid and accurate
      method.

PMID- 8286110
TI  - Presence and possible role of c-ras and nuclear (c-fos and c-jun) proto-oncogene
      products in preimplantation embryonic development in mice.
AB  - The presence and possible role of products of nuclear (c-fos and c-jun) and c-ras
      proto-oncogenes were investigated in preimplantation embryonic development in
      mice. Polyclonal antibodies to c-fos or c-jun proto-oncogene products did not
      affect development of in vitro-cultured embryos from two-cell to morula or from
      morula to late blastocyst stages. However, v-H-ras monoclonal antibody (mAb) to c
      ras protein (p21), although it did not inhibit the development of in vitro
      cultured embryos from two-cell to morula stages, it significantly (P < .001-.005)
      inhibited the development of morula to late blastocyst stages in a dose-dependent
      manner. The effects of v-H-ras mAb were specific, since immunoabsorption with
      synthetic ras peptide completely blocked inhibitory effects of v-H-ras mAb.
      Neither c-fos nor c-jun antibodies reacted with specific proteins corresponding
      to c-fos (62 kDa) and c-jun (39 kDa) products on the Western blots of various
      murine ova/embryos extracts. However, the c-fos and c-jun antibodies reacted with
      62 and 39 kDa protein bands, respectively, on the blot of NIH 3T3 cells extract.
      The v-H-ras mAb specifically identified 21 +/- 3 kDa protein corresponding to c
      ras p21 on the blots of early as well as late blastocyst extracts. The rat
      control ascites IgG1 did not react with any protein band on the blots of various
      ova/embryo extracts. The reactions of v-H-ras mAb on the Western blots of
      blastocyst extracts were specific, since immunoabsorbed antibody was unable to
      react with any specific band on blots of early or late blastocyst extract. These
      results were further confirmed by immunoprecipitation procedure utilizing v-H-ras
      mAb. Again, the v-H-ras mAb immunoprecipitated a 21 kDa band from early as well
      as late blastocyst extracts. The rat control ascites IgG1 did not react with any
      band corresponding to p21 in the immunoprecipitation procedure. These results
      suggest that the specific products of nuclear proto-oncogenes, the c-fos and c
      jun, are not detected in murine ova and preimplantation embryos, and the
      respective antibodies do not inhibit embryogenesis, indicating that they may not
      play a major role in early embryonic development. On the other hand, the product
      of c-ras proto-oncogene is specifically expressed in the blastocyst-stage embryos
      and may have a possible role in preimplantation embryonic development in mice.

PMID- 8286111
TI  - Nuclear transfer and electrofusion in bovine in vitro-matured/in vitro-fertilized
      embryos: effect of media and electrical fusion parameters.
AB  - In this study, micromanipulation and electrofusion conditions for the cloning of
      in vitro-produced bovine embryos (here after termed IVM/IVF embryos) derived from
      in vitro-matured (IVM) and in vitro-fertilized (IVF) oocytes were established.
      The effect of DC field strength on the fusion rate was tested in a model system
      using pronuclear stage embryos in which a cytoplasmic vesicle was removed and
      reinserted. Efficient fusion (80%) was obtained by applying a pulse of 1.75 kV/cm
      for 40 microseconds. In vitro development of manipulated pronuclear stage embryos
      was as efficient as that of unmanipulated control embryos. Different fusion media
      were compared in the cloning procedure, using IVM oocytes as recipients and
      blastomeres from day 6 IVM/IVF donor embryos. Zimmermann cell fusion medium
      reduced the lysis of nuclear transfer embryos compared to F300 (5% vs. 25%). The
      effects of drugs disrupting the microfilaments and microtubuli were determined.
      Neither the addition of cytochalasin B (CCB) for 1 hr in the postfusion medium
      nor incubation of donor blastomeres with nocodazole had a significant effect on
      the fusion or cleavage rate of the nuclear transfer embryos. Additional
      experiments demonstrated that there was no difference in developmental potential
      between nuclear transfer embryos allowed to develop in vitro or in vivo and that
      the embryos gave a 15% pregnancy rate in recipient cattle.

PMID- 8286112
TI  - Uptake and metabolism of pyruvate and glucose by individual sheep preattachment
      embryos developed in vivo.
AB  - The uptake of pyruvate and glucose by individual sheep oocytes and preattachment
      sheep embryos at each state of development up to the hatching blastocyst was
      determined using a microfluorescence technique. After an initial increase at
      fertilization, pyruvate uptake was relatively constant (approximately 15
      pmol/embryo/h) from the zygote through to the morula. Upon blastocyst formation
      and hatching, there were significant increases in uptake (39 pmol/embryo/h, P <
      0.001; and 53 pmol/embryo/h, P < 0.001, respectively). In contrast to that of
      pyruvate, glucose uptake was very low (approximately 1 pmol/embryo/h) up to the
      time of genome activation (eight- to 16 cell stage), after which there were
      significant increases in uptake at each successive stage of development. By the
      hatching blastocyst stage, glucose uptake had reached 54 pmol/embryo/h. The
      ability of day-7 hatching blastocysts to oxidize pyruvate and glucose was
      determined indirectly by measuring the production of lactate when either
      substrate was present as the sole energy source. Unlike the mouse blastocyst,
      which has a considerable oxidative capacity for both pyruvate and glucose, the
      day-7 sheep blastocyst showed limited ability to oxidise either substrate.
      Rather, in the sheep blastocyst, 65% of pyruvate and 98% of glucose taken up
      could be accounted for as lactate. Such low levels of substrate oxidation appear
      to be inconsistent with the energy requirements of the proliferating
      preattachment ruminant blastocyst. The utilization of alternative substrates at
      the blastocyst, such as amino acids, is proposed.

PMID- 8286113
TI  - Modulation of embryonic Na(+)-K(+)-ATPase activity and mouse preimplantation
      development in vitro in media containing high concentrations of potassium.
AB  - The effect of various potassium concentrations (ranging from 1.4 mM to 30 mM K+)
      in modified Tyrode's medium on the culture of mouse zygotes obtained after in
      vitro fertilization to the blastocyst stage was examined. A clear dose-dependent
      negative effect of increasing K+ concentrations on the preimplantation embryonic
      development in vitro was found. We have previously shown that significantly more
      two-cell embryos reach the blastocyst stage when cultured during the second day
      postinsemination in medium supplemented with taurine. Because taurine, an amino
      acid that abounds in the reproductive tract, has been reported to inhibit the
      enzyme Na(+)-K(+)-adenosine triphosphatase (Na(+)-K(+)-ATPase), we used two other
      conditions known to inhibit the Na(+)-K(+)-ATPase to study their effect on mouse
      embryo development. Culturing embryos during a short period (the second day
      postinsemination) in low extracellular K+ concentrations (1.4 mM) or in medium
      supplemented with ouabain (50 microM) showed positive effects similar to those of
      culturing in medium with taurine (10 mM). This beneficial effect of ouabain was
      found in various K+ concentrations tested, including the high concentrations
      present in the oviduct. Although the effects of low K+ and taurine can possibly
      be ascribed to their other cellular effects, the effect of ouabain shows that
      inhibition of the Na(+)-K(+)-ATPase during the two-cell stage in the mouse is
      beneficial for further embryonic development to the blastocyst stage.

PMID- 8286114
TI  - Sperm penetration through the zona pellucida of salt-stored hamster eggs is
      delayed.
AB  - One of the problems in assaying sperm capacitation is that live eggs mount a
      block to polyspermy at the zona pellucida. To circumvent this problem,
      researchers have started to use salt-stored eggs to assay sperm capacitation
      (Boatman et al., Gamete Res 19:19-29, 1988; Yoshimatsu et al., Gamete Res 21:115
      126, 1988). These researchers have demonstrated that the zonae of salt-stored
      eggs were penetrable by capacitated sperm, but they did not examine whether the
      timing of penetration of fully capacitated sperm was altered. This report shows
      that zona penetration by fully capacitated sperm is delayed in both short-term
      salt-treated eggs (2 hr) and in eggs stored in salt for > 2 days. These results
      indicate that the zona is modified when eggs are treated with a high-salt
      solution.

PMID- 8286115
TI  - Fertilization and early embryonic development in the blue fox (Alopex lagopus).
AB  - A total of 15 blue fox vixens aged 1-6 years were mated, 12 once on the first day
      of estrus and three a second time 48 hr after the first mating, and were killed 4
      hr to 8 days following mating. Ova were collected from the oviducts, evaluated by
      stereomicroscopy, and studied by transmission (TEM; N = 49, 12 vixens) or
      scanning (SEM, N = 11, three vixens) electron microscopy. At 0-3 days after
      ovulation, the ova had not cleaved and were at different stages of meiotic
      maturation. In about one-half of these ova, representing all stages of meiotic
      maturation, a decondensing sperm head without nuclear envelope or a small
      pronucleus with partial nuclear envelope was observed. No clear relationship was
      found between maternal meiotic stage and the stage of paternal pronucleus
      formation. Sperm tails were never identified in the ooplasm. Cortical granules
      were released after sperm penetration at early stages of meiotic maturation. Thus
      the block against polyspermic penetration was activated during maturation of the
      oocyte. The first two-cell stage appeared 4 days after ovulation (3 days after
      mating), the first four-cell stage the following day (day 5), and the first eight
      cell stage 6 days after ovulation (5 days after mating). In a single vixen mated
      late (7 days postovulation) two- to four-cell stages appeared the following day
      (day 8). This indicates that the time required for the first cleavage division
      decreases with increasing interval from ovulation to mating.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8286116
TI  - Ram spermatozoa cocultured with epithelial cell monolayers: an in vitro model for
      the study of capacitation and the acrosome reaction.
AB  - The effects of different epithelial cells, namely, hamster oviduct, sheep
      oviduct, and pig kidney epithelial cells (IBRS-2), on the viability, percentage
      of progressive motility (PPM), and acrosome reactions of ejaculated ram
      spermatozoa were investigated. Sperm aliquots were cultured on cells, cell
      conditioned medium 199, or control medium 199. The PPM of unattached spermatozoa
      was estimated after 0, 3, 6, 9, 12, and 24 hr of incubation at 37 degrees C under
      5% CO2 in air. Viability and the occurrence of true acrosome reactions were
      assessed using a triple-stain technique. Spermatozoa started to attach within 1
      hr of coculture with the hamster or sheep oviductal epithelial cell (OEC)
      monolayers, and these spermatozoa showed vigorous tail motion. No spermatozoa
      were found to attach to the IBRS-2 monolayer. The PPM of unattached spermatozoa
      cocultured with the various types of epithelial cell monolayers for 12 hr was
      significantly higher than that of spermatozoa incubated in conditioned media or
      medium 199 alone (54% in hamster OEC vs. 40% in conditioned; 68% in sheep OEC vs.
      38% in conditioned; 36% in control medium). On the other hand, after 24 hr of
      incubation, there were no differences in the PPM of spermatozoa cocultured with
      epithelial cells or incubated in conditioned media. The percentages of cells
      undergoing a true acrosome reaction reached maximum values (P < 0.05) in
      spermatozoa incubated for 9 hr in the presence of hamster OEC (22.5%) or for 12
      hr on sheep OEC (20.5%) monolayers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286117
TI  - Binding of a murine proteinase inhibitor to the acrosome region of the human
      sperm head.
AB  - Proteinase inhibitors are present in the various glands, tissues, and secretions
      of the male reproductive tract. Some of these inhibitors bind to the acrosomal
      region of the sperm, and their release during in vitro or in utero incubation
      suggests that they may play a role in capacitation. In the mouse, the binding
      site for a trypsin-acrosin inhibitor, the acceptor, has been implicated in
      capacitation, zona binding, and the acrosome reaction. This presentation
      demonstrates that a component, molecular weight approximately 20,000, on the
      human sperm head may recognize the murine inhibitor. Furthermore, the acrosome
      reaction can be induced in capacitated human sperm by immunoaggregation of bound
      murine inhibitor. The data indicate that the proteinase inhibitor binding site on
      the human sperm head may, as with a similar site on murine sperm, play a role in
      the early events of fertilization.

PMID- 8286119
TI  - Effects of electrical stimulation before or after in vitro fertilization on sperm
      penetration and pronuclear formation of pig oocytes.
AB  - The effects of exposure of pig oocytes to an electrical pulse-on sperm
      penetration and pronuclear formation were determined before or after in vitro
      fertilization (IVF). After in vitro maturation (IVM) or after collection from
      oviducts of unmated gilts, pig oocytes either were not exposed or were exposed to
      an electrical pulse (a 10 sec pulse at 4.0 Vmm-1 AC followed by a 30 microseconds
      pulse at 120 V mm-1 DC), followed 30 min later by IVF. The incidence of male
      pronuclear formation of both IVM and in vivo-matured oocytes at 12 hr after
      insemination was decreased from 59% and 100%, respectively, to 2% and 36%,
      respectively, by the electrical pulse, but the penetration rates (88-100%) and
      polyspermic rates (79-100%) were not affected by exposure to an electrical pulse.
      Similarly, when pig IVM oocytes were exposed to an electrical pulse at 6 hr after
      insemination, electrical activation did not decrease penetration rates (93% vs.
      90%), polyspermic rates (83% vs. 91%), or number of spermatozoa in penetrated
      oocytes (4.0 +/- 0.5 vs. 4.6 +/- 0.5) but did decrease the rate of male
      pronuclear formation from 58% to 18%. When oocytes were examined at 6 hr after
      insemination, 75% of them had been penetrated and resumed meiotic progression,
      but all sperm heads in penetrated oocytes were fully condensed or only partially
      decondensed. The percentage of penetrated eggs with multiple female pronuclei was
      increased when oocytes were exposed to an electrical pulse in all experimental
      series.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286118
TI  - Assessment of ram sperm mitochondrial function by quantitative determination of
      sperm rhodamine 123 accumulation.
AB  - A simple procedure is described for determining the functional state of ram sperm
      mitochondria by quantitative measurement of sperm rhodamine 123 (R 123)
      accumulation. Sperm were incubated with 1 microgram/ml R 123, and the accumulated
      R 123 was measured fluorimetrically after release from washed sperm by detergent
      lysis. Ram sperm R 123 uptake was maximal after 30 min of incubation and
      responded to changes in both sperm (P < 0.01) and R 123 (P < 0.01) concentration.
      There was a linear relationship (r = 0.98) between R 123 uptake and the
      proportion of cold-shocked sperm present in a sperm sample. R 123 uptake was
      unaffected by 20 mM 2-deoxyglucose or by 10 mM malonate (the latter being
      sufficient to reduce O2 uptake; P < 0.01). R 123 accumulation in ram sperm was
      reduced by 6 mg/ml sodium pentobarbitone (P < 0.05), by 1 microM 2,4
      dinitrophenol (P < 0.01), and by 0.05% Triton X-100 (P < 0.01). It is concluded
      that quantitative estimation of R 123 uptake complements oxygen uptake in
      detecting mitochondrial dysfunction in ram sperm. While it is largely unaffected
      by inhibition of glycolysis, and is less sensitive than oxygen uptake to
      trichloroacetic acid cycle inhibition, R 123 uptake is sensitive to factors
      directly reducing the mitochondrial membrane potential of ram sperm. It may
      therefore by useful in the evaluation of the effects of such membrane-mediated
      injuries as cold shock and freezing damage on ram sperm mitochondria.

PMID- 8286120
TI  - Calcium channels play a pivotal role in the sequence of ionic changes involved in
      initiation of mouse sperm acrosomal exocytosis.
AB  - The sequence of ionic changes involved in initiation of acrosomal exocytosis in
      capacitated mouse spermatozoa was investigated. Earlier studies demonstrated that
      a large influx of Na+ is required for exocytosis, this Na+ apparently being
      associated with an increase in intracellular pH (pHi) via an Na(+)-H+ exchanger.
      This rise in pHi may in turn activate calcium channels and permit the influx of
      extracellular Ca2+ needed to trigger acrosomal exocytosis. In the present study,
      the dihydropyridine voltage-dependent calcium channel antagonist nifedipine was
      able to inhibit significantly exocytosis in sperm cells treated in various ways
      capable of stimulating acrosomal loss. The monovalent cation ionophore monensin
      can promote Na+ entry required for both capacitation and acrosomal exocytosis, as
      demonstrated by using chlortetracycline to monitor changes in sperm functional
      potential. In the presence of 10 nM nifedipine, monensin treatment accelerated
      capacitation but was unable to trigger exocytosis. The requirement for
      internalization of a high concentration of Na+ can be bypassed by the addition of
      25 mM NH4Cl to raise the pHi of cells capacitated in 25 mM Na+ (insufficient Na+
      to support exocytosis under usual conditions). Again, introduction of nifedipine
      was able to inhibit exocytosis. In a third experimental approach, amiloride
      stimulated exocytosis in capacitated cells was significantly inhibited by
      nifedipine. In contrast to these treatments directed at specific mechanisms, the
      ability of the Ca2+ ionophore A23187 to promote more general entry of Ca2+ and
      thereby to accelerate capacitation and exocytosis was not inhibited by
      nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286121
TI  - Does the zona pellucida select spermatozoa from the medium with higher
      fertilizing potential?
AB  - The present study was carried out to test whether the zona pellucida selects
      spermatozoa with higher fertilization potential. Fertilization rates of mouse
      oocytes after sperm microinjection under the zona pellucida (SMUZ) of zona-bound
      spermatozoa and of spermatozoa incubated in the absence of oocytes and treated
      (acid-treated group) or not (control group) with acid Tyrode's solution were
      compared. SMUZ was performed at 15, 30, 60, and 90 min after the insemination of
      fresh oocytes required for selecting spermatozoa bound to the zona pellucida. At
      these times, the percentages of acrosome-reacted spermatozoa (PARS) were
      evaluated using the chlortetracycline fluorescence method. Fertilization rate in
      the three groups analysed increased from 25.9% to 47.3% in the control group,
      from 29.3% to 44.0% in the acid-treated group, and from 19.5% to 40.0% in the
      zona-bound group from 15 to 90 min after insemination, respectively. The global
      fertilization potential was significantly lower in the zona-bound group compared
      to the other two groups. The PARS in the zona-bound group at 15 (11.48 +/- 3.02),
      30 (16.74 +/- 3.71), and 90 (19.68 +/- 3.68) min after insemination were
      significantly (P < 0.05) lower than those found in the acid-treated group (39.26
      +/- 6.69, 38.20 +/- 6.24, and 42.83 +/- 5.39, respectively). At 90 min after
      insemination, the PARS in the zona-bound group was also significantly (P < 0.05)
      lower than the control group (36.72 +/- 4.51). No significant correlation between
      either time and PARS or PARS and fertilization rate was observed. It appears that
      the zona pellucida does not select from the medium spermatozoa with higher
      fertilization potential.

PMID- 8286122
TI  - Porcine zona pellucida ZP3 alpha glycoprotein mediates binding of the biotin
      labeled M(r) 55,000 family (ZP3) to boar sperm membrane vesicles.
AB  - The two M(r) 55,000 glycoproteins, ZP3 alpha and ZP3 beta, of porcine zona
      pellucida copurify as a preparation designated ZP3. Gamete binding assays have
      implicated ZP3 alpha, but not ZP3 beta, as participating in sperm-zona
      recognition events. We now report that boar sperm contain membrane-associated
      binding sites with specificity for ZP3 alpha. Biotin-labeled (b-) preparations of
      ZP3 bind to intact boar sperm in a saturable manner, with localization on the
      anterior head region. Membrane vesicles obtained from capacitated sperm by
      nitrogen cavitation retain b-ZP3 binding sites as determined by an enzyme-linked
      method employing alkaline phosphatase-conjugated strepavidin. In competitive
      binding assays using b-ZP3 (0.1 microgram/ml) as probe, heat-solubilized zonae
      and ZP3 were effective competitors, whereas the nonzona molecules fetuin and
      fucoidin were not. Digestion of ZP3 with endo-beta-galactosidase, an enzyme that
      trims polylactosamines, enhanced its affinity for membrane receptors. In contrast
      treatments such as chemical deglycosylation, pronase digestion, or disruption of
      disulfide bonds abolished the ligand activity of ZP3. Finally, purified ZP3 alpha
      was an at least 100-fold better antagonist than purified ZP3 beta. The results
      demonstrate that binding of b-ZP3 to isolated boar sperm membranes is mediated by
      sperm receptors with specificity for the ZP3 alpha macromolecular component and
      reveal a complex contribution of both carbohydrate and protein moieties toward
      the ligand activity of this sperm adhesive zona molecule.

PMID- 8286123
TI  - Gene imprinting during placental and embryonic development.

PMID- 8286124
TI  - IgG subclass concentrations and Gm allotypes in IgA-deficient and normal pregnant
      women.
AB  - IgG subclass concentrations were measured in the serum of 40 IgA-deficient (IgA
      concentration < 0.01 milligram) and 38 normal women in the second trimester of
      pregnancy. In the IgA-deficient group, 2 women were also deficient in IgG2 and
      IgG4, while a further 10 had very low concentrations of serum IgG4 only. These
      low IgG4 values were unrelated to the presence of anti-IgA antibodies. The
      incidence of low IgG4 values was significantly greater (p < 0.01) than in the
      control group where only 1 woman had low IgG4 and none had low IgG2. Mean values
      for total IgG, IgG1 and IgG3 were very significantly higher (p < 0.001) in the
      IgA-deficient group than in the control group. These differences were unrelated
      to Gm phenotype.

PMID- 8286125
TI  - Genetic polymorphisms of the A and B subunits of coagulation factor XIII in the
      Chinese population.
AB  - Coagulation factor XIIIA and XIIIB polymorphisms in a random population sample
      from Chengdu in southwest China (n = 121) were studied using isoelectric focusing
      in polyacrylamide gels followed by immunoblotting with enzyme immunoassay. The
      allele frequencies were as follows: FXIIIA*1 = 0.8719, FXIIIA*2 = 0.1240,
      FXIIIA*3 = 0.0041; FXIIIB*1 = 0.2727, FXIIIB*2 = 0.0165, FXIIIB*3 = 0.7107. The
      distribution of phenotypes of FXIII agrees with the Hardy-Weinberg equilibrium.
      Comparing these allele frequencies with those reported in other populations, it
      was found that the allele frequencies of FXIIIA*1 and FXIIIB*3 in the Chinese
      population were higher.

PMID- 8286126
TI  - Example of a woman with multiple intrauterine deaths due to anti-M who delivered
      a live child after plasmapheresis.
AB  - Serological and hematological investigations are reported for a woman who had
      multiple intrauterine deaths due to anti-M. The mother was group O Ns and the
      husband's cells were shown to be group O MSs. In the serological examination
      during the third pregnancy anti-M antibodies were identified in her serum. The
      antibodies comprised IgM saline agglutinin at a titer of 256 at 4 degrees C and
      IgG agglutinin reacted in an indirect antiglobulin technique at a titer of 4,096
      at 37 degrees C. After the intrauterine death at 14 weeks gestation of her fifth
      pregnancy she underwent plasmapheresis 6 times on a biweekly program.
      Approximately 2 liters of plasma were exchanged for 1 liter of plasma protein
      fraction and 1 liter of fresh frozen plasma. In her sixth pregnancy, intensive
      plasmapheresis was started from 2 months gestation and a total of 56 liters
      plasma were exchanged. The anti-M titer fell to 256. She delivered a live girl by
      induction of labor at 35 weeks. The child was group O MNs. Her red cells had a
      positive direct antiglobulin reaction and her serum contained IgG anti-M
      antibody. Phototherapy was carried out and the child developed normally.

PMID- 8286127
TI  - Antibody reactivity to synthetic peptides representing the principal neutralizing
      determinant of HIV-1 in mouse strains following repeated immunization with
      recombinant gp160.
AB  - The third variable region (V3) of the HIV-1 gp120 envelope molecule appears to
      represent a target for naturally occurring neutralizing antibodies in HIV-1
      infected individuals. In this report, we examined the extent of antibody cross
      reactivity to a panel of V3-based synthetic peptides in six inbred strains of
      mice following repeated immunization with a baculovirus-derived recombinant gp160
      (rgp160) preparation formulated with alum. The amino acid sequence of the rgp160
      used in these immunizations was based upon the HIV-1 IIIB (LAI) isolate.
      Following five injections with rgp160, all six strains developed antibodies to
      the homologous IIIB-based V3 peptides, designated 304-321 and RP135. However,
      antibody cross-reactivity to the other nonhomologous V3 peptides was either
      undetectable or limited among the strains of mice examined. No in vitro
      neutralizing activity against HIV-1 was observed in sera from any of the six
      inbred strains of mice that were examined. These results suggest that repeated
      immunization of mouse strains with a rgp160/alum formulation leads to
      nonneutralizing antibodies directed against the V3 region which remain
      predominantly type specific.

PMID- 8286128
TI  - [Apropos the pharmacological treatment recommended in the Fifth Report of the
      Joint National Committee on Detection, Evaluation and Treatment of High Blood
      Pressure].

PMID- 8286129
TI  - [Congenital cardiopathies in postchildhood. Cardiopathies operated on. A new and
      growing population].
AB  - Due to the continual progress being made in the surgical treatment of congenital
      heart diseases, very few symptomatic cardiac malformations can not now benefit
      from surgery, or more recently, from interventional catheterization. The result
      of such progress has led to an extraordinary change in survival patterns of
      congenital heart disease. With few exceptions, heart surgery is not curative.
      Residua and sequelae are the rule, and impose important medical, and sometimes
      surgical problems in the follow-up. Adequate control of this growing population
      is not easy within most of our adult cardiological departments. Adult patients
      with congenital heart disease represent a new area of cardiovascular interest.

PMID- 8286130
TI  - [The angiographic characteristics and extent of the coronary lesions in patients
      with residual ischemia following a myocardial infarct].
AB  - AIM OF THE STUDY: The aim of the present study was to analyze the angiographic
      findings of patients with residual ischemia after acute myocardial infarction
      (spontaneous angina versus ischemia stress induced), testing the following
      theoretical hypothesis: those patients with early spontaneous angina after acute
      myocardial infarction have singular angiographic characteristics that justify
      their clinical instability. PATIENTS: A consecutive group of 60 patients admitted
      in the Coronary Care Unit with acute myocardial infarction, all of them
      presenting signs or symptoms of residual ischemia, was divided into two
      subgroups: A--25 patients with spontaneous angina before discharge; B--35
      patients with myocardial ischemia (symptomatic or not) during exercise test
      performed before discharge. METHODS: The angiographic studies were analyzed
      according to following parameters: number of vessels with significant stenosis
      (more than 70%), involvement of the left anterior descending artery: "TIMI"
      score, presence of thrombi and morphology of the culprit lesion, presence of
      collaterals. RESULTS: We did not find any significant differences between the
      analyzed parameters. CONCLUSIONS: The present study does not disclose any
      significant differences related with coronary anatomy in patients with residual
      ischemia after acute myocardial infarction when we considered the two most
      frequent kinds of presentation: spontaneous angina or stress induced ischemia
      before discharge. Therefore the previous postulated hypothesis had not been
      confirmed.

PMID- 8286131
TI  - [A pulsed Doppler study of left atrial and ventricular inflow in 2 populations of
      normotensive and hypertensive subjects].
AB  - OBJECTIVE: Comparative analysis of left atrial and left ventricle Doppler inflow
      patterns in patients with essential systemic mild to moderate hypertension and
      normal global left ventricular systolic function. PATIENTS: A group of out
      patients with the diagnosis of hypertension referred to the Echocardiographic
      Laboratory of Egas Moniz Hospital in Lisbon. SETTING: Echocardiographic Doppler
      prospective study. MATERIAL AND METHODS: We studied a group of 50 patients with
      the diagnosis of mild to moderate arterial hypertension (Group H), which was
      compared with a population of 50 normal subjects (Group N). In each case we
      analysed the pulsed Doppler flow of the right upper pulmonary vein and the
      diastolic inflow of the left ventricular cavity. We calculated the peak
      velocities and time velocity integrals of the systolic, diastolic and atrial
      contraction waves of the pulmonary venous flow and also the systo-diastolic
      velocity and time velocity integral ratios. In the transmitral Doppler flow
      analysis we evaluated the peak velocities and time velocity integrals of the
      early (E wave) and late (A wave) waves, and their time velocity and velocity
      ratio. We assessed also the isovolumic relaxation time and left ventricular mass
      index. RESULTS: In groups N and H the peak velocity of the pulmonary venous flow
      systolic wave was 0.53 +/- 0.15 cm/sec and 0.75 +/- 0.10 cm/sec (p = 0.01),
      diastolic wave was 0.50 +/- 0.10 cm/sec and 0.41 +/- 0.09 cm/sec (p = 0.03) and
      atrial contraction wave was 0.18 +/- 0.03 cm/sec and 0.35 +/- 0.08 (p = 0.001),
      with a systo-diastolic ratio of 1.06 +/- 0.10 and 1.83 +/- 0.10 (p < 0.001),
      respectively. In these two groups the time velocity integral of the pulmonary
      venous flow systolic wave was 14.4 +/- 2.6 cm and 17.8 +/- 1.8 cm (p = 0.001),
      the diastolic wave was 12.5 +/- 3.2 cm and 9.3 +/- 1.3 cm (p = 0.05) and the
      atrial contraction wave was 4.4 +/- 0.07 cm (p = 0.001), with a systo-diastolic
      ratio of 1.1 +/- 0.16 and 1.9 +/- 0.12 (p < 0.001), respectively. For the group H
      and considering the three subgroups, hypertensive patients without anatomical or
      functional alterations, with isolated diastolic dysfunction and with left
      ventricular hypertrophy associated to diastolic dysfunction, the velocity systo
      diastolic ratio was 1.08 +/- 0.12, 1.57 +/- 0.08 (p < 0.01) and 2.4 +/- 0.08 (p <
      0.01) and 2.4 +/- 0.08 (p < 0.001), the systo-diastolic time velocity integral
      ratio was 1.22 +/- 0.17, 1.72 +/- 0.13 (p < 0.01) and 2.4 +/- 0.15 (p < 0.001),
      the peak velocity of the atrial contraction wave was 0.28 +/- 0.07, 0.3 +/- 0.08
      (p < 0.01) and 0.43 +/- 0.07 (p < 0.001) and its time velocity integral was 4.6
      +/- 0.06 cm, 5.6 +/- 0.07 cm (p < 0.01) and 7.0 +/- 0.08 cm (p < 0.001).
      CONCLUSIONS: Pulsed Doppler study of pulmonary venous flow is significantly
      abnormal in patients with arterial hypertension. This abnormal pulmonary venous
      flow pattern has a close relationship with structural and functional alterations
      of the left ventricle. Combined analysis of the pulsed Doppler inflow at these
      two cardiac anatomical levels is fundamental to understand the pathophysiology of
      hypertensive heart disease.

PMID- 8286132
TI  - [The remote noninvasive assessment of left ventricular diastolic pressure by
      pulsed Doppler echography--the importance of the time of mitral protodiastolic
      deceleration].
AB  - To find a possible correlation between the transmitral diastolic flow, obtained
      by pulsed Doppler echocardiography, and left ventricular end-diastolic pressure
      (LVedP), we studied 95 patients (p) (58 +/- 9 years), with coronary artery
      disease (76 p) and dilated cardiomyopathy (19 p). P with atrial fibrillation,
      heart rate > 100 b/m or mitral regurgitation > 2+/4+ were excluded. We analyzed E
      and A wave peak velocities (v), time-velocity integrals (i) and diastolic filling
      intervals. Restriction to filling pattern was considered in the presence of an E
      wave deceleration time (DecT) < or = 120 ms (Group B- 22 p); the other 73 p
      (group A) ranged from abnormal relaxation to normal diastolic patterns, with DecT
      > 120 ms. RESULTS: -LVedP ranged from 3 to 38 mmHg in group A and from 16 to 39
      mmHg in group B. In group A, the Ai/Ei ratio showed a significant linear
      correlation with the LVedP (r = 0.83, y = 14 chi + 2); Ai/El ratio > 1.0
      identified pts with LVedP > 18 mmHg with a sensitivity of 85% and a specificity
      of 98%. In group B, there was a correlation between LVedP and the inverse ratio
      of integrals (Ei/Ai) (r = 0.72), as well as Ev/Av ratio (r = 0.69). CONCLUSIONS:
      In myocardial active relaxation abnormalities, Ai/Ei ratio increases
      proportionally to LVedP. A short DecT (< or = 120 ms) identifies a subgroup of p
      with predominant impairment of LV compliance and high filling pressures, in which
      the atrial contribution decreases as LVedP rises. Thus, whatever the prevailing
      mechanism of diastolic dysfunction, echo-Doppler transmitral diastolic flow can
      provide a noninvasive assessment of LVedP.

PMID- 8286133
TI  - [The complications associated with the performance of heart catheterizations
      (diagnostic and therapeutic). The results in the Hemodynamics Laboratory of
      Hospital de Santa Marta].
AB  - OBJECTIVES: To evaluate the morbidity and mortality with cardiac catheterization
      (diagnostic and intervention). DESIGN: Retrospective analysis of complications
      occurring within 24 h of a cardiac catheterization, in three consecutive years
      (1989-1991). SETTING: Patients admitted to the Haemodynamic Laboratory of Santa
      Marta Hospital-Lisbon. PATIENTS: 4014 patients submitted to diagnostic and
      interventional procedures. MATERIALS AND METHODS: Registry analyze in order to
      obtain the following data: pathology, age, vascular approach and complications of
      cardiac catheterization. RESULTS: In three years there were 4014 cardiac
      procedures. 53.6% were performed in patients with coronary artery disease, 20%
      with valvular heart disease, 8.1% with congenital heart disease, 16.1% with
      others pathologies and 2.2% revealed normal vessels in coronary angiography. The
      incidence of ischemic heart disease was progressively higher in the studied
      years: 51.9% in 1989, 52.4% in 1990 and 55.2% in 1991. Data from population age
      showed the same tendency: mean age was 51, 53 and 55 years, respectively. Femoral
      approach was attempted in 95% of the studies, and the axillary in 2.15%.
      Complications of diagnostic and interventional cardiac procedures occurred in 3%
      of the patients. Dead occurred in 0.14%; arrhythmia, 0.37%; vascular, 0.14%;
      vasovagal/pyrogen reactions, 0.73%; myocardial infarction, 0.05%; and others,
      1.58%. CONCLUSION: The diagnostic and interventional cardiac catheterization in
      experienced laboratories are a safe procedure with a reduced incidence of major
      complications.

PMID- 8286134
TI  - [A case of rupture of the free wall of the left ventricle occurring at a district
      hospital. The problems of communication with heart surgery centers].
AB  - This is a report of an acute myocardial infarction complicated with rupture of
      the free wall of the left ventricle. Some comments concerning diagnosis and
      therapy are added, with emphasis in the correct communication of community
      hospitals with the centers of cardiac surgery.

PMID- 8286135
TI  - [Paroxysmal atrial fibrillation and flutter and "occult" arterial hypertension.
      The importance of the ambulatory monitoring of the blood pressure. Apropos 2
      cases].
AB  - The authors describe two hypertensive patients with paroxysmal auricular flutter
      or fibrillation. The arterial hypertension was suspected because of a
      hypertensive response in a treadmill stress test, confirmed by a 24-hour blood
      pressure ambulatory monitoring and there was no damage in target organs. They
      focus that auricular flutter/fibrillation may be related to "occult
      hypertension".

PMID- 8286136
TI  - [Infectious endocarditis. The usefulness of echocardiography in the clinical
      picture of endocarditis].

PMID- 8286138
TI  - [New concepts in the treatment of congestive heart failure. Introduction].

PMID- 8286137
TI  - [Jose Maria Grande, physician, naturalist and politician. Patron of the Hospital
      de Portalegre].

PMID- 8286139
TI  - [Digitalis glycosides and diuretics in the treatment of congestive heart
      failure].

PMID- 8286140
TI  - [Angiotensin I-converting enzyme inhibitors in the treatment of congestive heart
      failure].

PMID- 8286141
TI  - [Nitrates in the treatment of congestive heart failure].
AB  - In this revision article, after referring the mechanisms of action of nitrates in
      the relief of heart failure symptoms, the author presents the results of the
      controlled studies which show the beneficial effect of the nitrates on heart
      failure symptoms and mortality. The results of the therapy with nitrates are
      compared to other heart failure therapies, such as the administration of the
      angiotensin conversion enzyme (ACE) inhibitors. In spite of the highly favourable
      results regarding mortality shown by the latest studies with ACE inhibitors, the
      nitrates still occupy an essential place in the therapy of patients with heart
      failure, since they have the advantage of a much faster onset of action and are
      more effective in relieving symptoms than ACE inhibitors. Ancient problems of
      controversial clinical significance are focused such as resistance and tolerance
      to nitrates, its clinical implications, and possible methods for prevention of
      nitrate tolerance and resistance are reviewed. Finally, the author suggests some
      dosage and administration routes of the nitrates in heart failure, giving
      attention to particular clinical groups, namely the elderly and other special
      cases, and their adverse events.

PMID- 8286142
TI  - [Calcium antagonists in the treatment of congestive heart failure].
AB  - The authors present a revision of the clinical studies using calcium antagonists
      to treat chronic heart failure. They analyse cases where calcium antagonists seem
      to be of no use (and can even have an adverse effect), particularly in patients
      with significant left ventricular systolic dysfunction, with normal afterload,
      high levels of renin, very high levels of right atrium pressure or low sodium. On
      the opposite, patients with increased afterload or valvular regurgitation can
      receive some benefit, although care must be taken in the administration of this
      kind of drugs. New calcium antagonists may show more benefit because they seem
      not to stimulate the adrenergic system and do not have significant negative
      inotropic effects. They conclude with a reference to the multiple situations that
      can be the basis for heart failure, suggesting that probably, in the future,
      therapy shall be more individually tailored and that in some cases calcium
      antagonists can be included in such therapy.

PMID- 8286143
TI  - [Mechanical support in the treatment of heart failure].

PMID- 8286144
TI  - Recurrent aphthous ulceration: virological and immunological aspects.

PMID- 8286145
TI  - Macrophage heterogeneity in development and differentiation.
AB  - Macrophages, which are heterogeneous populations existing in various tissues and
      organs, are responsible for numerous metabolic, immunological, and inflammatory
      processes in physiological and pathological conditions. Macrophage heterogeneity
      is observed from early ontogeny. Primitive macrophages first develop in yolk sac
      hematopoiesis, by-passing the differentiation pathway of the monocytic series to
      differentiate into fetal macrophages in various tissues. Monocytic cells are a
      minor cell population in the early fetal period, and increase in the late stage.
      Primitive/fetal macrophages proliferate and survive in loco in the fetal period
      and reside as resident macrophages after birth. In adult animals, monocytes are
      differentiated from promonocytes derived from pluripotent stem cells in bone
      marrow. Monocytes exude in inflammatory foci and differentiate into exudate
      macrophages, exudate-resident macrophages and peroxidase-negative macrophages,
      but not resident macrophages. Monocyte-derived macrophages are a short-lived and
      non-proliferating cell population. Tissue (resident) macrophages proliferate and
      maintain their population by self renewal. In mice rendered monocytopenic by
      administration of a bone-seeking isotope, strontium-89, tissue resident
      macrophages maintained their population for 6 weeks. Resident macrophages in the
      liver formed glucan-induced granulomas in this monocytopenic model. In macrophage
      colony stimulating factor (M-CSF)-deficient mice (op/op), monocytes as well as
      tissue macrophages are deficient. However, M-CSF-independent tissue macrophages
      and Langerhans/dendritic cells are present in the defective condition of monocyte
      differentiation into macrophages, indicating that differentiation pathways of
      tissue macrophages and nonlymphoid dendritic cells are different from those of
      monocytes. In cultures supplemented with various colony stimulating factors
      (CSFs), heterogenous macrophage populations were generated. These in vivo and in
      vitro findings suggest that the phenotypic and functional heterogeneity of
      macrophages reflects complex macrophage differentiation mechanisms and that CSFs
      are important factors in the formation of a microenvironment for macrophage
      differentiation.

PMID- 8286146
TI  - Migration of LHRH neurons derived from the olfactory placode in rats.
AB  - Using the olfactory placode of 12.5- and 14.5-day-old (E12.5, E14.5) rat embryos,
      we examined the migration of LHRH neurons by in vivo intraventricular
      transplantation and in vitro organotypic culture systems. In the transplantation,
      the olfactory placode of E12.5 embryos was co-transplanted with the cerebral
      cortex and also with medial basal hypothalamus (MBH). LHRH neurons that had
      migrated into the co-transplanted brain tissues were fusiform, but those that had
      moved into the neuro-mesenchymal tissue were polyhedral. The migration occurred
      most conspicuously in the MBH. In our in vitro studies, we used E14.5 embryos;
      their vomeronasal organ was cultured with MBH, the olfactory cortex, and the
      septum of the telencephalon in two systems (piled-culture with an intervening
      transferrable membrane and co-culture). Among these brain tissues, the MBH was
      the most effective in inducing the development and migration of LHRH neurons. We
      further found synaptic junctions of immunonegative nerve fibers on immunoreactive
      LHRH neurons located in the septum of E16.5 and 17.5 embryos. These findings
      suggest that the MBH may lead the intraseptal migration of LHRH neurons by
      yielding certain substances after introducing the neurons into the medial aspect
      of forebrain vesicles. The early development of the neuronal connection may
      further promote the migration of LHRH neurons.

PMID- 8286147
TI  - A study on the submandibular ganglion of the monkey with special reference to
      ultrastructural changes after lingual nerve sectioning.
AB  - This study describes normal light and electron microscopic features of the monkey
      submandibular ganglion. The intraglandular ganglion is composed of a collection
      of smaller ganglia distributed mainly at the hilum of the submandibular gland:
      one or two large ganglia were often found along with the main duct, while the
      smaller ones were located at the periphery. All ganglion cells were covered by
      satellite cells. Ultrastructurally, the ganglion cells showed the usual features
      of autonomic neurons, being round to oval with a prominent nucleus and nucleolus.
      Their cytoplasm contained numerous randomly distributed organelles. Occasional
      ganglion cells showed darkened dendrites. The majority of the synapses observed
      were of the axo-dendritic type, although the axo-somatic type was not uncommon.
      In the latter, the axon terminals were sometimes seen to deeply invaginate the
      soma of the ganglion cells forming synaptic contacts. Non-synaptic desmosome-like
      junctional complexes were common between the ganglion cells. Following the
      severance of the lingual nerve, the ganglion showed structural alterations
      beginning 1 day after the operation. The earliest sign of change was the increase
      in the number of macrophages surrounding the ganglion. Three and five days after
      the lingual nerve sectioning, the number of darkened dendrites considerably
      increased. Associated with this change were neuronal nuclei displaying irregular
      outlines. Other changes involved the disintegration of the preganglionic fibres
      and their axon terminals. The latter were observed to be engulfed by the
      infiltrated macrophages and Schwann cells. By 7 days after the preganglionic
      parasympathectomy, the ganglion cells resumed normal features, suggesting the
      acute and reversible nature of the transneuronal degeneration of the monkey
      submandibular ganglion cells. This is further supported by the absence of cell
      death during the period examined.

PMID- 8286148
TI  - Postnatal development of periodontal innervation in rat incisors: an
      immunohistochemical study using protein gene product 9.5 antibody.
AB  - The postnatal development of innervation in the lingual periodontal ligament of
      rat incisors was investigated by immunohistochemistry using an antibody against
      protein gene product 9.5 (PGP 9.5), a neuron-specific protein. Immunostaining
      with the antibody enabled the clear demonstration of chronological alteration in
      the distribution and maturation of nerve terminals after birth. At 1 day after
      birth, thick nerve fibers showing PGP 9.5-immunoreactivity first appeared in the
      loose connective tissue corresponding to the future periodontal ligament, without
      forming an apparent terminal structure. At 4 days, two portions became
      distinguishable in the lingual periodontal ligament: alveolus- and tooth-related
      parts being comparable to those in the adult ligament. The immunoreactive nerve
      fibers increased in density and appeared to extend more incisally. Those
      restricted to the alveolus-related part showed ramifications with a small number
      of expanded or bulbous portions, and terminated among the periodontal fibers.
      Characteristic dendritic and expanded terminals, similar to Ruffini endings in
      the adult ligaments, began to occur in the lingual periodontal ligament at 7 days
      after birth and gradually increased in number until day 11 when the incisal edges
      emerged in the oral cavity. At approximately 15 days after birth, nerve endings
      possessing morphological features similar to Ruffini endings in adult rats were
      recognizable in the entire length of the periodontal ligament. After the eruption
      of first molars, the periodontal Ruffini endings drastically increased in number,
      and by the time the occlusion between the first molars was established, became
      identical in distribution and density to those seen in the lingual periodontal
      ligament of adult rat incisors. These findings suggest that the mechanical
      stimuli due to tooth eruption and occlusion might be a prerequisite for the final
      differentiation and maturation of the periodontal Ruffini endings.

PMID- 8286149
TI  - Fixation of biological specimens by high hydrostatic pressure.
AB  - We investigated whether or not high hydrostatic pressure could be used as a new
      method of histological fixation. Various high hydrostatic pressures from 200 to
      800 MPa (Mega Pascal) were applied to fresh organs including heart, liver,
      intestine and kidney of mice, and the gross and light microscopic findings were
      compared with those of organs fixed with formalin and those without fixation. The
      specimens processed with pressure were firm, elastic and pale, somewhat
      resembling the formalin fixed ones. Light microscopic examination revealed well
      preserved fine structures in the heart and intestine subjected to approximately
      450 MPa for 15 min at room temperature, although the fine structures of the liver
      and kidney were not well preserved. The enzyme activity of alkaline phosphatase
      was rarely preserved in the formalin-fixed kidney, but could be easily detected
      in kidneys processed with a pressure of 450 MPa. We conclude that high
      hydrostatic pressure can be used as a fixative, both for preserving the basic
      tissue structure in certain organs and for retaining the biological activity of
      an enzyme. In addition, the fixation is uniform, the processing is fast, and the
      materials can be handled safely. At present, however, its application is limited
      to specific organs.

PMID- 8286150
TI  - The existence and distribution of melanocytes in the periodontal ligament of the
      mongrel dog.
AB  - The existence and distribution of melanocytes in the periodontal ligament of the
      mongrel dog were investigated. Melanocytes were found in the periodontal ligament
      of the maxillary incisor and premolar segments. Melanocytes in the periodontal
      ligament varied in number, and generally appeared as dendritic or elongated cells
      with several, long cytoplasmic processes. These melanocytes were always
      distributed closer to the tooth root side of the periodontal ligament than the
      alveolar bone side, but did not contact the cementum. Melanocytes were
      longitudinally distributed in the apical half of the periodontal ligament. There
      were no findings suggestive of a relationship between melanocytes and epithelial
      rests of Malassez or other cellular elements of the periodontal ligament.
      Although some parts of the gingival mucosa of all dogs in this study showed
      pigmentation, no relationship was seen between melanocytes in the periodontal
      ligament and those in the gingival mucosa. This is the first report of
      melanocytes in the periodontal ligament under normal conditions.

PMID- 8286151
TI  - A hydrophilic resin-embedding method for light and electron microscopic detection
      of tissue anionic sites with cationic colloidal iron: as applied to mouse Paneth
      cells.
AB  - A cationic colloidal iron method was introduced for electron microscopic
      detection of anionic sites in hydrophilic resin-embedded specimens, and the
      method was applied to Paneth cells of the mouse jejunum. Mouse jejunal blocks
      were embedded in hydrophilic acrylic resin (LR White), cut into ultrathin
      sections, stained with the diluted cationic colloidal iron, and exposed to osmium
      vapor. The jejunal tissues, including the Paneth cells, embedded in hydrophilic
      resin were reactive to the fine cationic colloidal iron. At pH value 1.5, fine
      electron dense colloidal iron deposited along the rims of the secretory granules
      and the Golgi apparatus of the Paneth cell. Colloidal particles distributed on
      the osmiophilic reticular structures in the rim and in dot-like fashion lined the
      border between the granular core and rim. At pH value 4.0, ribosomes reacted to
      cationic colloidal iron particles in addition to the granular rims and Golgi
      apparatus. At pH 7.0, even the cores of the secretory granules were stained. Semi
      thin sections prepared from the LR White-embedded specimens and stained at pH 1.5
      with the diluted (1:3 in volume) cationic colloidal iron showed sufficient
      Prussian blue reaction for light microscopy in the rims of Paneth granules and
      mucus of goblet cells. This method is therefore useful for correlative light and
      electron microscopic detection of tissue anionic sites, including sulfate,
      carboxyl and phosphate groups, at various pH values.

PMID- 8286152
TI  - Influence of exogenously administered oxytocin on prolactin-producing cells in
      adult male rats as revealed by immuno-electron microscopy.
AB  - Prolactin-producing cells (PRL cells) identified by immuno-electron microscopy
      were studied in male rats with chronic intraperitoneal injection of synthetic
      oxytocin (OT). The PRL cells are usually classified into three types: the
      immature type containing round secretory granules about 100 nm in diameter with
      poorly developed cell organelles; the intermediate type containing medium-sized
      (150-250 nm in diameter) secretory granules with moderately developed cell
      organelles; and mature type containing large pleomorphic secretory granules
      ranging from 300 to 700 nm in diameter with well-developed cell organelles. In
      male rats, the intermediate type comprises typical PRL cells that constitute
      about 50% of all immunoreactive PRL cells. Chronic intraperitoneal OT
      administration to rats caused morphologically hypertrophic and hyperfunctioning
      PRL cells which are identified as mature type PRL cells. The frequency of
      occurrence of the mature type PRL cells increased after treatment. The contents
      of pituitary and serum PRL as measured by radioimmunoassay essentially paralleled
      the morphological results. These data indicate that OT may play a physiological
      role in PRL secretion as a releasing factor, and that OT administration causes
      the interconversion of the three types of PRL cells, indicating the mature type
      to be at the most activated state of secretory function.

PMID- 8286153
TI  - Scanning electron microscopic studies of smooth muscle cells and their collagen
      fibrillar sheaths in empty, distended and contracted urinary bladders of the
      guinea pig.
AB  - This study was performed to clarify the structure of muscle cells and the
      arrangement of surrounding collagen fibrils in the guinea-pig urinary bladder by
      scanning electron microscopy with two different chemical-digestion methods.
      Morphological changes in the muscle cells and the collagen fibrils under
      stretching and contraction were also examined. The smooth muscle cells in the
      empty bladder were shaped like an unbranched stick 130 microns long. They
      elongated to 360 microns in the distended bladder, and 48 microns in the
      contracted bladder. These cells have short lateral processes touching the
      neighboring muscle cells in an end-to-side fashion. Longitudinal striations on
      the cell surface due to rows of caveolae and dense bands were recognizable
      irrespective of the extended or contracted conditions. Transversely arranged
      wrinkles, which were considered to be produced by surface enfolding during
      contraction, were marked on the surface of contracted muscle cells. Each muscle
      cell was accommodated by a thin lace-like sheath made of both separate and small
      bundled collagen fibrils. That part of the fibrils in one sheath often extended
      to participate in another sheath suggested that the collagen sheaths not only
      modulate cell shape but also provide a structure serving the co-ordinated motion
      of neighboring muscle cells.

PMID- 8286154
TI  - The effect of dietary fat on the developing brain.

PMID- 8286155
TI  - Assessment of short stature in very low birthweight children.
AB  - The aims of this study of short very low birthweight (VLBW) children at or after
      8 years of age were to determine: (i) if there were any unsuspected organic
      causes for their growth failure; and (ii) whether any children might be suitable
      for treatment with synthetic growth hormone. Thirty-seven of 195 (19%) VLBW
      children seen at 8 years had heights < 10th centile, and of these only 40%
      (10/25) of families offered an assessment were concerned enough to have the child
      fully evaluated. No child had an unsuspected organic cause of short stature. The
      children's parents were significantly shorter than expected for Caucasians (mean
      parental height s.d. score = -1.06 (s.d. 0.72), t = -5.9, P < 0.001). On average,
      the bone age of the short children was delayed by 14.9 months (s.d. 18.8 months)
      compared with chronological age (t = -3.4, P < 0.01). When compared with their
      parents, the children's mean height s.d. score for their bone age was not
      significantly different (mean height s.d. score for bone age = -0.83 (s.d. 1.3),
      t = 0.6, NS). Only three children qualified for treatment with synthetic growth
      hormone; all three had been small for gestational age at birth and had
      birthweights < 1000 g. In conclusion, in short VLBW children, only a minority of
      families and children are likely to be concerned enough about short stature to be
      fully assessed; an unsuspected organic cause for growth failure is unlikely, and
      only a few will qualify for synthetic growth hormone therapy.

PMID- 8286156
TI  - Short-term outcome of mechanically ventilated infants weighing more than 2499 g
      at birth: a population based study.
AB  - Very little data exist describing the neonatal outcome of infants of birthweight
      2500 g or more who require mechanical ventilation. Our aim was to collect
      population-based data on such infants in New South Wales (NSW), and to monitor
      their neonatal morbidity, mortality to 1 year of age and the associated risk
      factors. The study group (NICUS infants) comprised all 341 infants weighing >
      2499 g who were admitted to the seven neonatal intensive care units in New South
      Wales and mechanically ventilated for 4 h or more between 1 January and 31
      December, 1987. Two groups of infants emerged: those who were preterm and mostly
      had hyaline membrane disease, and term and post-term infants for whom the most
      common problem was 'perinatal asphyxia'. The most important factors associated
      with dying were a birthweight of over 3499 g (OR = 2.6; CI 1.03-6.6) and a 1 min
      Apgar score < 4 (OR = 4.8; CI 1.4-16.9). Study group mothers were significantly
      more likely than all NSW mothers to have had a spontaneous abortion in the
      previous pregnancy (P < 0.01), a pre-existing medical condition or an obstetric
      complication in this pregnancy, or a Caesarean section for this delivery (P <
      0.001). This is the first population-based study of high-risk neonates without
      congenital anomalies to clearly document the worsening prognosis associated with
      a birthweight over 3499 g. Further research should be directed towards
      identifying prenatal and perinatal factors which might minimize the morbidity and
      mortality in this group of babies.

PMID- 8286157
TI  - Has the prevalence of asthma symptoms increased in Australian children?
AB  - This paper estimates whether an increase has occurred in the prevalence of asthma
      symptoms and diagnosed asthma in Australian children over the past two decades.
      Seventeen population-based studies undertaken in Australia since 1969 were
      reviewed. Inclusion criteria were studies using population samples of children
      aged 5-12 years, with standardized questionnaire measurements. Data from serial
      National Health Surveys were also examined for trends in recent and chronic
      asthma. The prevalence of recent (12 month) and cumulative wheeze increased,
      showing a significant correlation with year of study (r = 0.78 and r = 0.79,
      respectively). Diagnosed asthma showed a smaller but still significant increase
      (r = 0.65). The trends observed indicated that diagnosed asthma and reported
      wheeze have increased by almost 1% per year over the past two decades. Data since
      1980 have provided estimates of bronchial hyperreactivity (BHR), but no trend was
      observed. Substantial increases were noted in the National Health Surveys, with
      recent asthma prevalence in children aged 5-14 increasing from 3.3% in 1983 to
      8.3% in 1989, and chronic asthma prevalence increasing from 4.5% in 1977 to 15.2%
      in 1989. The findings of this review suggest an increase in the prevalence of
      asthma symptoms in children, but these observations could also be explained by
      changes in diagnostic fashion and an increased awareness of asthma symptoms.

PMID- 8286158
TI  - Variation in selected childhood surgical procedures: the case of tonsillectomy
      and management of middle ear disease.
AB  - We examined rates of the most common ear, nose and throat (ENT) surgical
      procedures among NSW residents under 15 years of age, against a background of
      concern for the relevance of differences in clinical practice to cost and quality
      of health care. We found significant (P < 0.01) increases in the rate of
      procedures involving myringotomy (from 5.8/1000 to 7.6/1000) or adenoidectomy
      (from 5.6/1000 to 6.3/1000) between 1986 and 1989/90. Over this period the
      proportion of ENT procedures which involved myringotomy also increased
      significantly (P < 0.01) from 53 to 60%. We found significant (P < 0.01)
      differences in procedural rates between health areas when aggregated into inner
      and outer metropolitan and rural groups with the mean rate of procedures
      involving myringotomy highest in the outer metropolitan group in both years. The
      difference was not due to variation in patient insurance status, per capita
      hospital bed or staff numbers. We found no evidence that the National Health and
      Medical Research Council Tonsillectomy and Adenoidectomy Guidelines (first
      published in 1982) have been effective in influencing clinical practice. The rate
      of tonsillectomy had been declining in NSW since the late 1970s but has remained
      stable in recent years. Surgical intervention for middle ear disease is
      increasing.

PMID- 8286159
TI  - Surfactant replacement therapy in neonates less than 32 weeks gestation: effect
      on neonatal intensive care resource utilization.
AB  - The effect of synthetic surfactant (Exosurf) replacement on complications from
      hyaline membrane disease (HMD) in infants < 32 weeks gestation and their resource
      utilization within a neonatal intensive care unit was studied in 1991-92. A
      control group was selected from infants admitted to the same unit during the
      preceding 3 years when Exosurf was not available. The infants were controlled for
      gestation, weight and severity of HMD. Infants given Exosurf had a significant
      reduction in the incidence of pulmonary interstitial emphysema (PIE), and a
      marginal decrease in the incidence of pneumothorax. They required fewer days on
      the ventilator and consumed less of the scarce financial resources. There was no
      difference in the mortality rate among the two groups. The changes seen were more
      evident among those infants between 30 and 31 weeks gestation, compared to those
      < 28 weeks.

PMID- 8286160
TI  - The socio-economic context of child injury in Australia.
AB  - After the first year of life, injury is the leading cause of mortality in
      children and adolescents in Australia and a major cause of morbidity and
      hospitalization. Studies from Europe and North American and more recently New
      Zealand have demonstrated that injury rates differ between different socio
      economic groups, with a relatively consistent pattern of higher rates being found
      in lower socio-economic groups. To date, the pattern of child injury morbidity by
      socio-economic group has not been studied in Australia. Eighteen months of data
      from Brisbane and Melbourne collections of the National Injury Surveillance Unit
      data base were analysed and linked to census data from each postcode in the
      collecting area to calculate injury rates. Injury rates for each postcode were
      correlated with measures of disadvantage derived from the same census data. There
      was a consistent pattern of moderately strong statistically significant
      associations (Pearson correlation coefficients generally 0.30-0.60) found between
      measures of disadvantage and injury rate at the postcode level of aggregation.
      This association was present across cities, age groups, type of injury and for
      those hospitalized as well as those treated as outpatients. It is apparent that
      residence in a low income area is a significant predictor of child injury in
      Australia.

PMID- 8286161
TI  - An epidemiological survey of SIDS in the Sydney metropolitan area.
AB  - Records of 1049 cases of Sudden Infant Death Syndrome (SIDS) (100%) in the Sydney
      metropolitan area (SMA) from 1980 to 1989 were analysed in relation to ambient
      temperature, geographical distribution and socio-economic scale. The SIDS rate
      varied between eastern and western Sydney and between statistical subdivisions;
      it peaked sharply in July, coinciding with the monthly mean minimum daily
      temperature (MMMDT; 6.5 and 5.4 degrees C, respectively). The inverse linear
      relationship between the SIDS rate and the MMMDT for the regions and the
      subdivisions was highly significant (P < 0.001). The SIDS rate showed a
      significant inverse linear relationship to two socio-economic scales (allotment
      and house value) for 82 of the 87 suburbs (94%) of the SMA. Temperature,
      indicative of cold weather, was the major factor determining SIDS rates, and
      this, together with socio-economic factors, largely explains the observed
      geographical distribution of SIDS rates in the SMA.

PMID- 8286162
TI  - Paediatricians' reports to general practitioners: should parents receive copies?
AB  - The aim of this study was to determine whether it was helpful for parents to
      receive a copy of the letter written by the paediatrician to the general
      practitioner (GP) when a child was referred to a paediatric outpatient department
      for the first time or with a new problem. A randomly allocated sample of 40
      intervention patients and 49 comparison patients was seen 2-4 weeks following the
      consultation in a semi-structured home interview conducted by a researcher who
      did not know the group allocation. Although significant differences in parent
      knowledge were not detected, parent satisfaction with the consultation was
      improved. No parent reported being upset or worried by the contents of the
      letter, and none of the paediatricians required extra time to explain aspects of
      the letter in an additional consultation, although the possibility of this was
      offered. There seem to be advantages in sending a letter copy to parents of
      children presenting with a wide range of conditions.

PMID- 8286163
TI  - Measles vaccine efficacy study in a Canberra high school: a study following a
      measles outbreak.
AB  - An outbreak of measles which occurred in Canberra between October and December,
      1991, was investigated to estimate the public health utility of the vaccine. The
      measles vaccine efficacy was determined for the 13-15 year old children in a
      selected high school. During the outbreak, at least 82 Canberra children
      contracted measles. Teenage males accounted for 56% of total cases, and 22% of
      cases were confirmed by serology. The vaccine coverage in the high school studied
      decreased with increasing school years, varying from 85.8% in Grade 8 to 79.2% in
      Grade 10. The highest attack rate occurred in Grade 10 (66/1000). The vaccine
      efficacy for age 13-15 was estimated to be 72% (95% Cl, 45-86%) but varied from
      67 to 73%. Measles remains a serious disease of childhood in Australia. The
      elimination of measles is only partly dependent on the vaccine coverage of
      children. Issues relating to the effectiveness of vaccine are also important. A
      two dose vaccine strategy with the second dose of measles, mumps, rubella vaccine
      (MMR), given preferably in the last year of primary school or the first year of
      high school, is supported by the findings of this study.

PMID- 8286164
TI  - Lack of agreement between two methods of measuring haemoglobin.
AB  - Haemoglobin values are reported by the current generation of blood gas analysers
      used in many intensive care units. A comparison of one such machine against a
      reference found that there was a mean difference of 1.32 g/dL (95% confidence
      intervals -2.75-0.9 g/dL) between the values reported. Haemoglobin values
      reported by blood gas machines may be inaccurate.

PMID- 8286165
TI  - Molecular characterization of beta-thalassaemia in Singaporean Chinese:
      application to prenatal diagnosis.
AB  - Sixty-five beta-thalassaemia genes from 14 unrelated Chinese beta-thalassaemia
      major patients and 37 Chinese beta-carriers were analysed by allele-specific
      oligonucleotide (ASO) hybridization after DNA amplification by the polymerase
      chain reaction (PCR). Six mutations were studied and are represented by 49.2% of
      codon 41-42, 30.8% of IVSII #654, 6.2% of 17 beta, 3.1% of IVSI #5 (G-->C) and
      1.5% of -28 TATA box. The complete mutations responsible for beta-thalassaemia
      major in 13 of our 14 affected families were identified. For these families
      prenatal diagnosis at 10 weeks gestation using DNA amplification and ASO
      hybridization will replace the globin chain biosynthesis technique at 19 weeks
      gestation. Using ASO analysis, our results indicate that 5 oligo-probes (41-42,
      II-#654, 17 beta, IVSI-#5 and -28) allow determination of beta-thalassaemia
      mutations in 59/65 (90.8%) of the Singaporean Chinese studied.

PMID- 8286166
TI  - Intracranial choriocarcinoma causing precocious puberty and cured with combined
      modality therapy.
AB  - Precocious puberty can be caused by hormonally active tumours, which may arise
      intracranially. Treatment of these intracranial lesions traditionally involves
      biopsy and radiotherapy. Chemotherapy has been used recently, although
      radiotherapy has been given irrespective of the response to chemotherapy. We
      report a case of precocious puberty in an 8 year old boy due to a malignant
      intracranial germ cell tumour. Although one could speculate that he was cured by
      such combined modality therapy, the patient was left with several long-term
      problems. Radiotherapy was a major cause of these complications. Radiotherapy is
      now thought unnecessary for most extracranial germ cell tumours, as chemotherapy
      alone is curative in most patients. Therefore it seems appropriate to consider
      the elimination of radiotherapy for patients with intracranial disease.

PMID- 8286167
TI  - Williams syndrome: a clinical study of children and adults.
AB  - Eighteen individuals in Western Australia with Williams syndrome were surveyed.
      Nine were adults. The majority (72%) presented initially because of developmental
      delay. The diagnosis was made at an average age of 35 months and in over half the
      cases was made by general paediatricians. Two-thirds of those surveyed had a
      significant cardiac murmur and eight had features of supravalvular aortic
      stenosis. Reduced peripheral circulation was found in 22%. One half had mild
      musculoskeletal abnormalities, joint contractures being the most common. Chronic
      or recurrent urinary symptoms were present in one-third of cases. Adults tended
      to be on a lower height centile and were more obese compared to children. The
      early diagnosis of Williams syndrome remains elusive. A wide range of
      complications may develop.

PMID- 8286168
TI  - Deletion of the terminal segment of the long arm of chromosome 4 with aortic
      stenosis.
AB  - A dysmorphic Chinese baby girl was found to have deletion of the long arm of
      chromosome 4 (46XX, del[4] q33-->qter). A review of various case reports of
      deletion of the long arm of chromosome 4 is reported and the clinical features
      are identified and compared. The earlier reports on this condition were that of
      deletion of the terminal segment of the long arm with break point occurring at
      q31. Since 1981, cases of deletion with break point at q33 have been reported.

PMID- 8286169
TI  - Colloid cyst of the 3rd ventricle as a cause of acute neurological deterioration
      and sudden death.
AB  - A 13 year old girl presented with a 24 h history of headache and vomiting. There
      were no focal neurological signs. The diagnoses considered were vascular
      headache, meningitis and subarachnoid haemorrhage. Lumbar puncture revealed clear
      cerebrospinal fluid under high pressure and subsequent cerebral computed
      tomography (CT) scan revealed hydrocephalus. Death occurred some hours after the
      lumbar puncture. Autopsy revealed a colloid cyst of the 3rd ventricle causing the
      hydrocephalus. Cerebellar tonsillar herniation was present. This case is reported
      because although 3rd ventricular colloid cysts are a recognized cause of acute
      neurological deterioration and sudden death, they rarely present in childhood. In
      this case, it is considered that lumbar puncture may have hastened death by
      increasing brain-stem compression due to cerebellar tonsillar herniation. It
      raises the question of whether cerebral CT scan, where readily available, should
      be performed prior to lumbar puncture. Pathologically, colloid cysts may be
      easily missed if the brain is examined fresh as the cysts are fragile and have a
      tendency to be destroyed or fall out.

PMID- 8286170
TI  - Liver disease in association with neonatal lupus erythematosus.
AB  - This report describes a patient with neonatal lupus erythematosus (NLE) in whom
      there was multisystem involvement including neonatal hepatitis. The hepatitis,
      defined pathologically as a giant cell hepatitis, presented with severe
      cholestasis, was unrelated to other known causes of neonatal hepatitis and
      resolved spontaneously by 6 months of age. Both mother and infant were positive
      for Sjogren syndrome A+B antibodies (SS-A[Ro] and SS-B[La]) as well as having
      high titres of antinuclear antibody (ANA). Three of the four cases described in
      the one previous report of this association were also ANA positive. This antibody
      may be a marker for the development of the hepatitis. Maternal and infant ANA
      status should be determined in cases labelled as idiopathic neonatal hepatitis to
      exclude undiagnosed maternal SLE as a cause of neonatal cholestasis.

PMID- 8286171
TI  - Learning disabilities and vision.

PMID- 8286172
TI  - Safety aspects of food additives.

PMID- 8286173
TI  - Antigenuria following Haemophilus influenzae type B vaccination.

PMID- 8286174
TI  - Renal candidiasis: possible aetiology for fungal ball formation.

PMID- 8286175
TI  - [The emergency treatment of voluminous laparoceles].

PMID- 8286176
TI  - [Perioperative pain and stress: a comparison between video laparoscopic
      cholecystectomy and "open" cholecystectomy].
AB  - Pain and endocrine-metabolic response to surgical stress, during surgery and in
      the early postoperative period, was compared in two groups of patients affected
      by gallstones and randomly assigned to Laparoscopic Cholecystectomy or Open
      Cholecystectomy. Pain was assessed by the VAS method also taking into account the
      need of analgesic administration in the postoperative period. The so called
      "stress hormones" (Prolactin (PRL), Cortisol (CORT), Human Growth Hormone (HGH))
      and glycaemia were monitored during surgery and in the first postoperative 24
      hours. The minimal invasive technique of laparoscopic cholecystectomy accounted
      for a very limited analgesic administration. In the intraoperative period
      laparoscopic cholecystectomy plasma hormone levels overlapped the open
      cholecystectomy ones, while in the postoperative period a constant increase in
      PRL and CORT levels was registered in the open cholecystectomy group
      demonstrating a prolonged stressful condition. The end results of this study show
      that laparoscopic cholecystectomy has major advantages than open cholecystectomy
      in the treatment of gallstones as far as pain and endocrine-metabolic response
      are concerned.

PMID- 8286177
TI  - Spontaneous rupture of the liver.
AB  - A case of spontaneous hepatic rupture associated with bacterial
      cholangiohepatitis, an entity not previously described as an etiologic factor, is
      reported and the literature reviewed. Awareness of the pathophysiology of this
      process and avoidance of certain procedures are important parts of the surgical
      armamentarium.

PMID- 8286178
TI  - [Squamous-cell carcinoma of the thyroglossal duct. A clinical case].
AB  - The authors report a rare case of squamous cell carcinoma arising in a
      thyroglossal duct cyst. The lesion is a malignancy arising directly from the
      lining epithelium of the thyroglossal duct remnant and as a rule has a poor
      prognosis with survival ranging from few months to few years.

PMID- 8286179
TI  - [Multiple primary malignant tumors of the larynx and lung].
AB  - The association of laryngeal and pulmonary neoplasms is one of the most frequent
      among multiple primary malignant tumors and represents an important problem in
      terms of prevention and diagnosis. The present study involves 22 cases of
      associated tumors observed from January 1st 1977 and December 31st 1992. All the
      patients involved were male, average age 62 years, who had been treated for
      laryngeal cancers, mostly laryngeal epidermoid carcinoma. Pulmonary cancers
      (simultaneous, synchronous, metachronous) were diagnosed in all these subjects
      and one patient presented 2 autonomous bronchial lesions which arose in different
      periods. Five patients out of 22 (23%) are still alive and with no evidence of
      disease (NED), 2 more patients are alive although not disease-free. After
      reporting some considerations regarding the neoplastic association involving the
      larynx and the lung as well as the increased risk of pulmonary neoplasm in those
      patients treated for supraglottic lesions, the authors emphasize the importance
      of personal and family history for cancer and suggest a classification of the
      risk to develop a second malignancy in these patients.

PMID- 8286180
TI  - [Parotid metastases of malignant tumors of the head].
AB  - Tumors of the head as well as other distant tumors may metastasize to the lymph
      nodes of the parotid gland. Metastases from head malignancies are much more
      frequent than those arising in distant organs. The authors report their
      experience in three cases of parotid lymph nodal metastases from head neoplasms:
      nasal septum carcinoma, left external auditory canal carcinoma and right
      suborbital skin melanoma. In two cases nodal metastases appeared after the
      treatment of the primary malignant tumor; in one case metastases were
      simultaneous to it. All patients were treated surgically (total parotidectomy
      with facial nerve preservation) and in two cases a submaxillary and functional
      neck dissection was carried out. Only one patient is alive and disease-free at
      three years from operation. The authors believe that total parotidectomy
      performed for nodal metastases involving the parotid gland is to be considered a
      true "parotid dissection", either "curative" or "prophylactic", depending on
      whether it is carried out when lymph nodes are palpable or not.

PMID- 8286181
TI  - [Cystosarcoma phyllodes of the breast: clinical cases].
AB  - The authors report their experience in the management of 8 cases of cystosarcoma
      phylloides of the breast observed between January 1979 and December 1986 in the
      Surgical Department of the University of Bari. This uncommon breast pathology,
      which stands halfway between benign (adenofibromas) and malignant (carcinomas)
      tumors presents considerable difficulties in terms of diagnosis particularly
      problematic for the small-sized lesions. The authors stress the need of a
      surgical treatment which takes into account women aesthetic desire assuring at
      the same time a complete exeresis. The latter includes the sacrifice of at least
      1 cm thick normal breast tissue to prevent the frequent local relapses.

PMID- 8286182
TI  - [Adenomyomatosis of the gallbladder: the authors' personal experience].
AB  - The authors report on a particular affection of the cholecyst wall known as
      adenomyomatosis. Having observed seven cases in the last three years they analyse
      the most suitable diagnostic methods and treatment.

PMID- 8286183
TI  - [The role of echography in the determination and monitoring of ductal ectasia in
      nipple discharge].
AB  - In this study a good sensibility of ultrasound in identifying ductal disease was
      demonstrated. We evaluated the relationship between nipple discharge and ductal
      ectasia and the importance of the ectasia in maintaining nipple discharge. From
      our data the hypothesis of a possible role of oestroprogestinic hormones in the
      genesis or maintaining of ductal ectasia emerged.

PMID- 8286184
TI  - [Intestinal infarct: a critical review of the cases observed in the decade of
      1981-1991].
AB  - The authors consider the causes of bowel infarction and report the up-to-date
      diagnostic tools for optional treatment. They verify management and outcome of 97
      cases treated during the last decade.

PMID- 8286185
TI  - [Secondary bacterial peritonitis: a diagnostic and therapeutic update].
AB  - In spite of the availability of new powerful antibiotics, intraabdominal sepsis
      still has a high mortality rate (20-50%). With regards to postoperative
      peritonitis, the referred high mortality rate is due to a late recognition and a
      consequently late treatment. The causes for late diagnosis are: uncertain
      clinical picture; misuse of analgesic drugs; reluctance of the surgeon to accept
      a failure. Moreover, many operated patients are under treatment with antibiotics:
      their misuse, particularly broad spectrum ones, is responsible for the selection
      of resistant bacteria. Age is another very significant prognostic factor:
      mortality rate is constantly higher in elderly subjects than in younger ones.
      Malnutrition, immunodepression, origin and location of sepsis, concomitant
      diseases, immunosuppressive treatments, delayed diagnosis, all can significantly
      affect clinical outcome. Probably the most important and less assessable factor
      is represented by the surgeon himself with his experience and technical accuracy:
      any mistake may worse patient's prognosis. Recently, many Authors have stressed
      the pathogenic relevance of the intestinal mucosa as a barrier, which may
      influence the clinical course.

PMID- 8286186
TI  - Programme for the control of acute respiratory infections. Recent developments.

PMID- 8286187
TI  - Dengue and dengue haemorrhagic fever. Dengue serotype 2 epidemic, Townsville,
      Queensland, 1992-1993.

PMID- 8286188
TI  - Mechanism of action of an orally administered platinum complex [ammine bis
      butyrato cyclohexylamine dichloroplatinum (IV) (JM221)] in intrinsically
      cisplatin-resistant human ovarian carcinoma in vitro.
AB  - Intrinsic resistance to existing clinical platinum drugs is a major cause of
      treatment failure; moreover, these agents have the drawbacks of cross-resistance
      and intravenous administration. The mechanism of intrinsic cisplatin resistance
      and the mechanism of circumvention of intrinsic resistance by a member (JM221) of
      the ammine/amine platinum (IV) dicarboxylate class of platinum complex was
      studied in intrinsically resistant (SKOV-3) and sensitive (41M) human ovarian
      carcinoma cell lines. JM221 reduced the cisplatin resistance factor nine- to 2.7
      fold, was more potent than cisplatin and showed marked time-dependent
      cytotoxicity. Cellular platinum accumulation was 20- to 40-fold greater (P <
      0.001), and DNA platination was fourfold greater (P < 0.02), immediately
      following 2 h equimolar exposure to JM221, compared with cisplatin. DNA platinum
      levels decreased following cisplatin exposure with a half-life approximating 48 h
      in both lines, while no net removal of DNA-bound platinum was recorded following
      JM221 exposure. JM221 caused DNA interstrand cross-linking, but this was 10-20%
      less frequent with JM221 than with cisplatin when expressed as a proportion of
      total DNA platinum lesions. Cisplatin DNA interstrand cross-linking was twofold
      greater in the intrinsically sensitive line (41M) than in the resistant line
      (SKOV-3) over a range of concentrations and time-points. Neither cellular
      platinum accumulation, levels of DNA platination nor the rate of removal of DNA
      bound platinum in the two cell lines related to their ninefold difference in
      cisplatin sensitivity. Intrinsic cisplatin resistance appears to be attributable
      to the inhibition of formation of bifunctional DNA lesions, while the
      circumvention of intrinsic resistance by JM221 seems to be the result of both
      improved transport properties and circumvention of DNA repair mechanisms.

PMID- 8286189
TI  - Photodynamic therapy-induced alterations in interstitial fluid pressure, volume
      and water content of an amelanotic melanoma in the hamster.
AB  - The effect of photodynamic therapy (PDT) on interstitial fluid pressure (IFP),
      tumour volume and water content was measured in melanomas grown in hamsters.
      Unlike control tumours, treated tumours exhibited a 40-60% increase in volume at
      1, 3 and 6 h post PDT. IFP also increased at 1 and 3 h after PDT, but decreased
      to 50% of control value after 24 h, presumably as a result of PDT-induced
      microcirculatory impairment.

PMID- 8286191
TI  - Leukaemia mortality in French communes (administrative units) with a large and
      rapid population increase.
AB  - Higher than expected leukaemia mortality rates have been observed in the persons
      under 25 years of age living in new towns in Britain. We report the results of a
      study on persons under 25 residing in all French communes (administrative units)
      in which a large and rapid population increase occurred between 1968 and 1990.
      The observed number of leukaemia deaths was 101, slightly less than the 112.0
      expected from national mortality statistics. There was no difference in the risk
      of leukaemia mortality according to sex, age, size of the population increase or
      region (Ile de France versus others).

PMID- 8286190
TI  - Duck hepatitis B virus infection, aflatoxin B1 and liver cancer in domestic
      Chinese ducks.
AB  - The oncogenicity of Duck hepatitis B virus (DHBV) is unclear since hepatocellular
      carcinomas (HCCs) have been reported only in domestic ducks in Qidong, an area of
      China where hepatitis B virus (HBV) and aflatoxin B1 (AFB1) are risk factors for
      liver cancer in man. In order to better define the association between DHBV
      infection, AFB1 and HCC we analysed a series of 16 duck liver samples collected
      from local farms in Qidong. HCC was found in eight and cirrhosis in one of these
      samples. Furthermore bile duct proliferation, characteristic of AFB1 exposure in
      ducks and other animal species, was found in these ducks. Integration of DHBV DNA
      into cellular DNA was observed in only one out of four DHBV positive HCCs,
      indicating that viral integration is not prerequisite for tumour development. In
      four remaining HCCs the polymerase chain reaction (PCR) failed to show any DHBV
      DNA suggesting that liver tumours do occur in polymerase chain reaction (PCR)
      failed to show any DHBV DNA suggesting that liver tumours do occur in these ducks
      in the absence of DHBV infection. In addition, AFB1-DNA adducts were detected by
      hplc-immunoassay in one such DHBV-negative tumour. In summary we demonstrate that
      risk factors other than DHBV, including AFB1 exposure, may be important in duck
      liver carcinogenesis in Qidong.

PMID- 8286192
TI  - Human papillomavirus and invasive cervical cancer in Brazil.
AB  - A hospital-based case-control study was undertaken to examine the role of human
      papillomavirus (HPV) in the development of invasive cervical cancer in Brazil.
      The study included 199 histologically confirmed incident cases and 225 age
      frequency-matched controls selected from a wide range of diagnostic categories. A
      polymerase chain reaction technique was used to detect HPV DNA in cervical
      specimens collected with spatula and brush. HPV DNA was detected in 84% of the
      cases compared with 17% of controls. Grouping HPV types 16, 18, 31 and 33, 66% of
      the cases were positive compared with only 6% of the controls. In addition to
      HPV, number of sexual partners, early age at first intercourse, parity and
      duration of oral contraceptive use were significantly associated with an
      increased risk of cervical cancer. A history of previous Papanicolaou smears was
      significantly associated with a decreased risk. After adjustment, only presence
      of HPV DNA, parity and history of previous smears remained as independent risk
      factors. The adjusted odds ratios of cervical cancer associated with HPV 16, 18,
      31, and 33 was 69.7 (95% confidence interval 28.7-169.6) and with unidentified
      types was 12.0 (5.1-28.5). The very high risks found in this study further
      implicate this virus in the aetiology of cervical cancer.

PMID- 8286193
TI  - Analysis of the IGF-II receptor gene copy number in breast carcinoma.
AB  - Insulin and the insulin-like growth factors (IGFs) may be important regulators of
      breast cancer growth. The IGF-II receptor is identical to the mannose 6-phosphate
      (Man-6-P) receptor, which is involved in lysosomal enzyme pathways. In order to
      determine whether the Man-6-P/IGF-II receptor gene copy number is altered in
      breast cancer we analysed specimens of invasive breast carcinoma from 51 patients
      by Southern blotting. No amplification of the receptor gene was observed whatever
      the clinical presentation of the tumour and irrespective of a concomitant
      amplification of c-erbB2 or int-2 genes in several tumours. As indicated by
      Northern blotting, the gene is transcribed in breast tumour tissues and non
      tumour breast tissue. These results suggest that the receptor gene is stable in
      breast carcinoma and that, if anything, the receptor involvement in breast cancer
      progression may be the result of a disregulation of its expression at a post
      transcriptional or post-translational level.

PMID- 8286194
TI  - Induction of transforming growth factor beta in hormonally treated human prostate
      cancer.
AB  - Transforming growth factor beta-1 (TGF-beta 1) has been proposed as a mediator of
      tumour growth in a number of tumours and cell lines including prostate, and in a
      recent study was shown to be up-regulated in the stroma of breast cancer tissue
      following treatment with the anti-oestrogen tamoxifen. Immunolocalisation of the
      intracellular form of TGF-beta 1 confirmed that the source of the stromal TGF
      beta 1 was the peritumoral fibroblasts. We present here the results of a study in
      which five patients with hormonally unresponsive prostatic carcinoma and seven
      patients responding to a luteinising hormone-releasing hormone analogue had
      prostate biopsies taken before and during treatment. These were stained for TGF
      beta expression prior to treatment and at either relapse or 3 months later
      respectively. Six of seven clinically responding tumours and three of five
      relapsed tumours showed up-regulation of extracellular TGF-beta 1, again
      primarily in the stroma, with no apparent up-regulation of intracellular TGF-beta
      1, TGF-beta 2 or TGF-beta 3. These data illustrate that the epithelial growth
      inhibitor TGF-beta 1 can be induced by hormonal manipulation in prostate cancer
      in vivo, and may continue to be up-regulated even after relapse. This suggests
      that relapse of hormonally treated prostate cancer may be associated with a
      failure of the epithelium to respond to stromal TGF-beta 1.

PMID- 8286195
TI  - bcl-2 in normal human breast and carcinoma, association with oestrogen receptor
      positive, epidermal growth factor receptor-negative tumours and in situ cancer.
AB  - The role of bcl-2 expression in solid tumours is as yet undefined. It was,
      therefore, the purpose of this study to investigate expression of bcl-2 protein
      in 111 human breast carcinomas using immunohistochemistry and the monoclonal
      antibody bcl-2 124. Expression was then compared with the established indicators
      of prognosis and biological behaviour in malignant breast disease. No
      relationship could be observed between bcl-2 and node status, tumour size,
      differentiation, type or age at excision. However, a strong positive relationship
      was seen between bcl-2 and oestrogen receptor (ER), with 70 of 88 (80%) bcl-2
      positive tumours being ER positive also, compared with seven of 23 (30%) bcl-2
      negative tumours being ER positive (P < 0.0001). The converse was found when bcl
      2 was compared with epidermal growth factor receptor (EGFR). A strong negative
      relationship was observed, with 26 of 88 (30%) bcl-2-positive tumours being EGFR
      positive, compared with 16 of 23 (70%) bcl-2-negative tumours being EGFR positive
      (P = 0.001), raising the possibility that bcl-2 is an ER-regulated gene. An
      inverse relationship was also found between bcl-2 and the oncogenes c-erbB-2 and
      p53. Thus, loss of bcl-2 expression in breast cancer is associated with a range
      of molecular markers of poor prognosis and may define part of an ER-negative,
      EGFR-positive phenotype.

PMID- 8286196
TI  - Cancer incidence in a population potentially exposed to radium-226 at Dalgety
      Bay, Scotland.
AB  - Cancer incidence in the Dalgety Bay area of Fife, Scotland, was examined
      following the detection of radium-226 particles by routine radiation monitoring.
      The study was confounded by rapid population growth, demographic change and the
      relatively high socioeconomic status of the Dalgety Bay population. Health Board
      Primary Care Division records were used to calculate population estimates and
      Carstairs deprivation score was used to adjust for socioeconomic characteristics.
      In the period 1975-90, 211 residents were registered as having cancer compared
      with 214.21 expected from Scottish national rates. Of specific cancers possibly
      associated with radiation, the incidence of stomach, liver, lung, bone, prostate,
      bladder and kidney cancer and lymphoma were lower than expected while colon,
      rectum, pancreas, skin, breast and thyroid cancer and multiple myeloma and
      leukaemia were higher. There were three cases of childhood leukaemia compared
      with 1.22 expected. The only statistically significant differences observed were
      for pancreas (11 cases, O/E 2.28), lung (25 cases, O/E 0.65) and non-melanoma
      skin (36 cases, O/E 1.50). Stomach cancer was of borderline statistical
      significance (four cases, O/E 0.40). Adjustments for socioeconomic factors
      accounted for the apparently low incidence of stomach and lung cancer and, to a
      lesser extent, skin cancer, which remained of borderline statistical
      significance. Results in relation to pancreas cancer were unchanged. The
      observations of raised incidence of pancreas and skin cancer arose in the context
      of a survey of 17 cancer sites, from which the finding of two or more
      statistically significant results is not unusual (P = 0.21), and the numbers of
      cases involved were small. The epidemiological evidence for an association
      between radiation exposure and pancreas cancer risk is weak. Stronger evidence
      exists for an association with skin cancer. In the present study the anatomical
      distribution of the 36 cases was similar to that found elsewhere in Scotland.

PMID- 8286197
TI  - Human ductal adenocarcinomas of the pancreas express extracellular matrix
      proteins.
AB  - Pancreatic ductal adenocarcinomas are characterised by a dense connective tissue
      reaction. To test the hypothesis that stroma components are synthesised and
      produced by the tumour cells themselves, eight cell lines as well as six
      xenografted tumours from human ductal adenocarcinomas of the pancreas were
      examined for the expression of extracellular matrix proteins (ECM), using cDNA
      probes and antibodies to collagen types I, III and IV, vitronectin, fibronectin,
      undulin and laminin. All tumour cell lines (CAPAN-1, CAPAN-2, AsPC-1, BxPC-3,
      PANC-1, PaCa-2, PaCa-3, PaCa-44) and xenografted human pancreatic tumours
      expressed at least one of the examined ECM at the RNA (collagen type IV > laminin
      = fibronectin = vitronectin > collagen type III > undulin > collagen type I) or
      protein level (collagen type IV = collagen type III > vitronectin > laminin >
      collagen type I = fibronectin > undulin). In nude mouse tumours expression of
      laminin and collagen I was most pronounced in well-differentiated carcinomas. In
      a few tumours, collagen type III, vitronectin and undulin were expressed on the
      luminal side of the neoplastic glands, suggesting loss of normal polar
      differentiation. Incubation with fetal calf serum modulated ECM RNA levels to a
      varying extent in all but one cell line (AsPC-1). The results suggest that human
      pancreatic ductal adenocarcinomas cells are capable of synthesising and producing
      extracellular matrix proteins in vitro and in vivo, but that the extent and
      pattern of ECM expression differs between the various tumours and conditions
      tested.

PMID- 8286198
TI  - Pancreatic trypsinogen and cathepsin B in human pancreatic carcinomas and
      associated metastatic lesions.
AB  - Expression of pancreatic trypsinogen and cathepsin B in 23 surgically resected
      pancreatic ductal adenocarcinomas was evaluated immunohistochemically, using a
      monoclonal antibody against human pancreatic trypsinogen and a polyclonal
      antibody against human cathepsin B. Fifteen of 20 invasive tubular
      adenocarcinomas (75%) expressed pancreatic trypsinogen in a coarse granular
      pattern located in the supranuclear cytoplasm of the carcinoma cells. In
      addition, metastatic lesions, including those in peripancreatic lymph nodes and
      neural plexuses, expressed pancreatic trypsinogen. In contrast, three intraductal
      (non-invasive) papillary adenocarcinomas did not express pancreatic trypsinogen.
      Cathepsin B expression was recognised in 14 of 20 invasive tubular
      adenocarcinomas (70%) in a fine granular pattern located diffusely in the
      cytoplasm of the carcinoma cells, while none of the three intraductal papillary
      adenocarcinomas had detectable cathepsin B. These findings suggest that
      pancreatic invasive ductal adenocarcinomas express pancreatic trypsinogen and
      cathepsin B immunoreactive peptides, raising the possibility that pancreatic
      trypsinogen and cathepsin B may act independently of each other in the process of
      carcinoma invasion and metastasis, like other different classes of proteases
      involved in the proteolytic modification of the matrix barrier.

PMID- 8286199
TI  - E-cadherin expression in basal cell carcinoma.
AB  - E-cadherin (E-CD) is a calcium-dependent cell-cell adhesion molecule which is
      expressed in almost all epithelial tissues. E-CD expression is involved in
      epidermal morphogenesis and is reduced during tumour progression of mouse
      epidermal carcinogenesis. It has been suggested that E-CD could play a role as an
      invasion-suppressor molecule. In the present work we have studied the E-CD
      expression in 31 patients with basal cell carcinoma (BCC) using an
      immunohistochemical technique with a monoclonal antibody (HECD-1) specific for
      human E-CD. E-CD expression was preserved in all specimens of superficial and
      nodular BCC, and was reduced in 10 of 15 infiltrative BCCs. A heterogeneous
      distribution of cells with different immunostaining intensity was more frequently
      observed in specimens of infiltrative BCC. These results suggest that E-CD might
      be related to the growth pattern and the local aggressive behaviour of BCC, and
      support the idea that E-CD might play a role as an invasion-suppressor molecule
      in vivo.

PMID- 8286200
TI  - Differential expression of myc, max and RB1 genes in human gliomas and glioma
      cell lines.
AB  - Deregulated expression of myc proto-oncogenes is implicated in several human
      neoplasias. We analysed the expression of c-myc, N-myc, L-myc, max and RB1 mRNAs
      in a panel of human gliomas and glioma cell lines and compared the findings with
      normal neural cells. The max and RB1 genes were included in the study because
      their protein products can interact with the Myc proteins, being thus putative
      modulators of Myc activity. Several gliomas contained c/L-myc mRNAs at levels
      higher than those in fetal brain, L-myc predominantly in grade II/III and c-myc
      in grade III gliomas. High-level N-myc expression was detected. In one small-cell
      glioblastoma and lower levels in five other gliomas. In contrast, glioma cell
      lines totally lacked N/L-myc expression. The in situ hybridisations revealed
      mutually exclusive topographic distribution of myc and glial fibrillary acidic
      protein (GFAP) mRNAs, and a lack of correlation between myc expression and
      proliferative activity, max and RB1 mRNAs were detected in most tumours and cell
      lines. The glioma cells displayed interesting alternative splicing patterns of
      max mRNAs encoding Max proteins which either suppress (Max) or augment (delta
      Max) the transforming activity of Myc. We conclude that (1) glioma cells in vivo
      may coexpress several myc genes, thus resembling fetal neural cells; but (2)
      cultured glioma cells expression only c-myc; (3) myc, max and RB1 are regulated
      independently in glioma cells; and (4) alternative processing of max mRNA in some
      glioma cells results in delta Max encoding mRNAs not seen in normal fetal brain.

PMID- 8286201
TI  - Combined evaluation of preoperative serum sialyl-Tn antigen and carcinoembryonic
      antigen levels is prognostic for gastric cancer patients.
AB  - We have found that elevation of preoperative serum sialyl-Tn antigen (STN) levels
      is associated with a poor prognosis for gastric cancer patients, and these high
      levels remain in the advanced stage of the disease. We have now examined findings
      with the combined assay of STN and carcinoembryonic antigen (CEA) levels with
      regard to prediction of the prognosis of gastric cancer patients. Serum CEA
      levels and STN levels were determined preoperatively in 349 Japanese patients
      with gastric cancer. The patients were divided into four groups: (A) the CEA (-)
      STN (-) group (CEA < or = 5 ng ml-1, STN < or = 45 U ml-1, n = 286); (B) the CEA
      (-) STN (+) group (CEA < or = 5 ng ml-1, STN > 45 U ml-1, n = 31); (C) the CEA
      (+) STN (-) group (CEA > 5 ng ml-1, STN < or = 45 U ml-1, n = 17); and (D) the
      CEA (+) STN (+) group (CEA > 5 ng ml-1, STN > 45 U ml-1, n = 15).
      Clinicopathological features and the prognosis of these groups were examined. The
      distribution of two markers showed no significant correlation. The patients in
      the CEA (+) STN (+) group (group D) had more advanced disease than the patients
      in CEA (-) STN (-) group (group A); tumour size was larger, serosal invasion was
      prominent, lymphatic and vascular involvement was frequent and the tumour was
      more infiltrative. Lymph node metastasis and hepatic metastasis were more common.
      Total gastrectomy was usually performed, and the non-curative rate was higher.
      The 5-year survival of patients in the CEA (+) STN (+) (group D) was 14.5 +/-
      9.5%, that is lower than that of patients in any other group [CEA (+) STN (-)
      (group C) 44.1 +/- 12.7% (P < 0.05); CEA (-) STN (+) (group B) 60.1 +/- 9.5% (P >
      0.05); CEA (-) STN (-) (group A) 77.6 +/- 9.5% (P < 0.05)]. This combined assay
      of these markers will aid in estimating the prognosis and selecting appropriate
      drugs and care for gastric cancer patients.

PMID- 8286202
TI  - Type-specific human papillomavirus DNA in abnormal smears as a predictor of high
      grade cervical intraepithelial neoplasia.
AB  - Human papillomavirus (HPV) typing and quantitation by polymerase chain reaction
      was performed on exfoliated cells from 133 women referred for colposcopy because
      of an abnormal smear. High levels of HPV 16 correctly predicted cervical
      intraepithelial neoplasia (CIN) grade II-III in 93% of its occurrences, but only
      59% of cases of CIN III were associated with high levels of this type. Eighty
      four per cent of CIN III lesions contained high levels of at least one of HPV
      types 16, 18, 31, 33 and 35, but the other types were less specific for CIN III
      than HPV 16. Overall HPV testing compared favourably with cytology for predicting
      high-grade CIN lesions, but it would appear that some combination of the two
      modalities will produce better performance than either alone. In particular, HPV
      testing appears to be helpful in determining which women with mildly abnormal
      smears have high-grade underlying lesions in need of immediate referral for
      colposcopy.

PMID- 8286203
TI  - Prognostic value of a novel circulating serum 90K antigen in breast cancer.
AB  - Monoclonal antibody SP-2 to the tumour-associated antigen 90K was generated by
      immunisation with conditioned medium of human breast cancer cells. We
      investigated whether circulating levels of 90K can influence the prognosis of
      patients with breast cancer. Serum samples were obtained from 425 patients with
      histologically proven breast cancer with no clinical evidence of disease after
      surgery (NED) and in 310 patients with metastatic disease. Serum 90K was
      determined by a new immunoradiometric assay (IRMA). Antigen levels in NED
      patients were elevated in 18.5% of cases, mean levels being higher than in
      healthy controls (P = 0.001). Among 375 evaluable patients, the 75-month overall
      survival for 90K-negative (< or = 11 U ml-1) and 90K-positive (> 11 U ml-1)
      patients was 78% and 53% respectively (P = 0.004). The prognostic value of 90K
      appeared to be limited to patients with node-positive disease. Number of
      metastatic axillary lymph nodes and level of 90K antigen were the only
      independent variables for predicting overall survival. Patients with metastatic
      breast cancer had elevated 90K in 51.3% of cases. High 90K levels were
      significantly associated with the presence of metastases to liver, shorter
      disease-free interval and younger age. We conclude that an elevated 90K antigen
      level in serum is a predictor of poor prognosis in breast cancer.

PMID- 8286204
TI  - Cyclic adenosine 3',5'-monophosphate-binding proteins in human ovarian cancers.
AB  - The aims of the present study were to characterise an assay for cAMP-binding
      proteins in ovarian cancer and then to measure levels in a series of tumours with
      a view to developing a potential prognostic indicator for this disease. Levels
      and types of binding proteins have been measured in cytosols from 50 ovarian
      tumours. Binding proteins were detected in all tumours but, as calculated from
      Scatchard analysis, binding levels ranged from 267 to 12,037 fmol per mg of
      cytosol protein (mean value of 4248 fmol mg-1). Dissociation constants of binding
      varied between 0.4 x 10(-8) and 5.9 x 10(-8) (mean value 2.3 x 10(-8)). Types of
      binding protein were detected by incubation with the photoaffinity ligand 8-N3
      [32P]cAMP, followed by polyacrylamide gel electrophoresis and autoradiography.
      Labelled proteins with molecular weights of 52, 48, 43, 39 and 37 kDa were
      identified in the cytosols. The proportion and pattern of bands detected varied
      between different cytosols. The significance of these findings awaits clinical
      follow-up of the patients.

PMID- 8286205
TI  - Protracted oral etoposide in epithelial ovarian cancer: a phase II study in
      patients with relapsed or platinum-resistant disease.
AB  - This phase II study evaluates the efficacy and toxicity of a prolonged schedule
      of oral etoposide in patients with measurable advanced ovarian cancer resistant
      to, or relapsed following, platinum-based chemotherapy. Forty-seven patients
      participated, 20 of whom had received more than one prior treatment. Seventy
      seven per cent had evidence of disease progression during or within 6 months of
      the previous chemotherapy. Initially, oral etoposide, 50 mg b.d. (regardless of
      patient size), was given for 14 days on a 21-day cycle. However, after
      encountering toxicity, the schedule was modified to 7 days' treatment escalating
      to 10 then 14 days if well tolerated. Among 41 assessable patients there were two
      complete and eight partial objective responses (24% response rate; 95% confidence
      interval 12-41%). Nine further patients (22%) had stable disease, four with a
      sustained fall of > 50% in CA-125. Median duration of response or stable disease
      was 35 weeks (range 21-49). Overall median survival was 41 weeks from study entry
      (range 2 to 96+ weeks). Toxicity for most patients was mild, but sporadic severe
      myelotoxicity occurred, with two treatment-related deaths. Risk factors for
      severe toxicity were: performance status 3; hepatic impairment; renal impairment.
      We conclude that oral etoposide has activity in platinum-resistant ovarian cancer
      and that it is a useful palliative therapy. It has significant toxicity which may
      be avoided by appropriate patient selection and an escalating-duration schedule.

PMID- 8286206
TI  - A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin
      2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than
      renal cancer and melanoma.
AB  - Our previous experimental studies have shown that the best approach to increase
      the biological anti-tumour activity of interleukin 2 (IL-2) is not co
      administration of another cytokine, but the association with immunomodulating
      neurohormones, in an attempt to reproduce the physiological links between
      psychoendocrine and immune systems, which play a fundamental role in the
      regulation of the immune responses. In particular, the association with the
      pineal neurohormone melatonin (MLT) has been shown to cause tumour regressions in
      neoplasms that are generally non-responsive to IL-2 alone. To confirm these
      preliminary results, a clinical trial was performed in locally advanced or
      metastatic patients with solid tumours other than renal cell cancer and melanoma.
      The study included 80 consecutive patients, who were randomised to be treated
      with IL-2 alone subcutaneously (3 million IU day-1 at 8.00 p.m. 6 days a week for
      4 weeks) or IL-2 plus MLT (40 mg day-1 orally at 8.00 p.m. every day starting 7
      days before IL-2). A complete response was obtained in 3/41 patients treated with
      IL-2 plus MLT and in none of the patients receiving IL-2 alone. A partial
      response was achieved in 8/41 patients treated with IL-2 plus MLT and in only
      1/39 patients treated with IL-2 alone. Tumour objective regression rate was
      significantly higher in patients treated with IL-2 and MLT than in those
      receiving IL-2 alone (11/41 vs 1/39, P < 0.001). The survival at 1 year was
      significantly higher in patients treated with IL-2 and MLT than in the IL-2 group
      (19/41 vs 6/39, P < 0.05). Finally, the mean increase in lymphocyte and
      eosinophil number was significantly higher in the IL-2 plus MLT group than in
      patients treated with IL-2 alone; on the contrary, the mean increase in the
      specific marker of macrophage activation neopterin was significantly higher in
      patients treated with IL-2 alone. The treatment was well tolerated in both groups
      of patients. This study shows that the concomitant administration of the pineal
      hormone MLT may increase the efficacy of low-dose IL-2 subcutaneous therapy.

PMID- 8286207
TI  - Pretreatment serum CRP and response to interleukin 2.

PMID- 8286208
TI  - Carotenoporphyrins as selective photodiagnostic agents for tumours.
AB  - The covalent binding of a carotene moiety to one phenyl ring and meso-tetraphenyl
      substituted porphyrins (see Figure 1) efficiently quenches the photosensitising
      activity of the porphyrin while a relatively large yield of fluorescence emission
      around 650 nm is retained. Pharmacokinetic studies performed with two
      carotenoporphyrins (CPs) and the corresponding porphyrins (Ps) in Balb/c mice
      bearing an MS-2 fibrosarcoma show that the two Ps give a high selectivity of
      tumour localisation (tumour/peritumoral tissue ratios of dye concentration
      ranging between c. 30 and 90 at 24 h after injection of 4.2-8.4 mumol kg-1 in a
      Cremophor emulsion) and photosensitive tumour necrosis upon red light
      irradiation. For the same injected doses, the two CPs show no tumour
      photosensitising activity even though they localise in the tumour in
      concentrations of the order of 10-40 micrograms g-1 at 24 h with
      tumour/peritumoral ratios larger than 10. Thus, the fluorescence emitted by these
      CPs in the tumour can be used for photodiagnostic purposes with no risk of skin
      photosensitisation. However, this approach is presently limited by the large
      accumulation and prolonged retention of the CPs in the liver and spleen.

PMID- 8286209
TI  - Stable bioenergetic status despite substantial changes in blood flow and tissue
      oxygenation in a rat tumour.
AB  - Experiments on s.c. rat tumours (DS sarcoma) were performed to determine whether
      chronic or acute changes in tumour perfusion necessarily lead to changes in
      tissue oxygenation and bioenergetic status since, as a rule, blood flow is
      thought to be the ultimate determinant of the tumour bioenergetic status. Based
      on this study, there is clear experimental evidence that growth-related or acute
      (following i.v. administration of tumour necrosis factor alpha) decreases in
      tumour blood flow are accompanied by parallel alterations in tissue oxygenation.
      In contrast, tumour energy status remains stable as long as flow values do not
      fall below 0.4-0.5 ml g-1 min-1, and provided that glucose as the main substrate
      can be recruited from the enlarged interstitial compartment. Perfusion rate seems
      to play a paramount role in determining energy status only in low-flow tumours or
      low-flow tissue areas.

PMID- 8286210
TI  - The relationship between carbon monoxide breathing, tumour oxygenation and local
      tumour control in the C3H mammary carcinoma in vivo.
AB  - The effect of acute carbon monoxide (CO) breathing on blood oxygenation and
      tumour hypoxia was related to the radiation response of the C3H/Tif mammary
      carcinoma. Blood gas analysis showed that CO breathing caused a time- and dose
      dependent formation of carboxyhaemoglobin (HbCO), a significant left shift of the
      oxygen dissociation curve and a reduction in tumour blood perfusion. These
      factors all contributed to a marked drop in tumour oxygen supply. In agreement
      with this, tumour hypoxia was found to be significantly increased: Microelectrode
      PO2 measurements showed a clear relationship between CO concentration and the
      proportion of low PO2 measurements (< or = 5 mmHg). The fraction of clonogenic
      hypoxic cells increased from 8% in air-breathing animals to 13%, 18% and 54% with
      75,220 and 660 p.p.m. CO respectively. The tumour hypoxia resulted in significant
      radiation modification. The local tumour control after single-dose and
      fractionated irradiation gave TCD50 enhancement ratios (relative to air-breathing
      controls) of 0.90, 0.85 and 0.89 for single dose and five or ten fractions given
      in 5 days (P < 0.005 for all values). For 15 fractions in 5 days with 6- 6- and
      12 h intervals, the TCD50 was similar in CO- and air-breathing mice, presumably
      as a consequence of insufficient reoxygenation during the short inter-fraction
      intervals. It is concluded that elevated HbCO levels to increased tumour hypoxia
      and that the induced hypoxia has a significant impact on the local tumour control
      also after fractionated irradiation.

PMID- 8286211
TI  - The combined effects of high-energy shock waves and cytostatic drugs or cytokines
      on human bladder cancer cells.
AB  - The effects of shock waves generated by an experimental Siemens lithotripter in
      combination with cytostatic drugs or cytokines on several bladder cancer cell
      lines were examined in vitro. Proliferation after treatment was determined with
      the 3-4,5-dimethylthiazol-2,5 diphenyl tetrazolium bromide assay. Dose
      enhancement ratios were calculated for each drug and each shock wave application
      mode in order to characterise the sensitising effect of shock wave pretreatment.
      The influence of the time between shock wave and drug treatment as well as the
      effects of different sequences of shock wave and drug treatment or concomitant
      treatment were assessed for selected combinations of cell lines and drugs. It was
      found that shock wave treatment could render certain cell lines more susceptible
      to subsequent cis-platinum, mitomycin C or actinomycin D incubation. Cell lines
      sensitive to tumour necrosis factor alpha or interferon alpha were further
      sensitised to these cytokines by shock wave pretreatment. The enhanced
      sensitivity to cis-platinum and actinomycin D decreased rapidly during the first
      hours after shock wave treatment. The antiproliferative effect was most
      pronounced after concomitant shock wave and drug treatment. The sensitisation to
      interferon alpha diminishes more slowly after shock wave exposure. From the
      results presented in this study it is concluded that transient shock wave-induced
      permeabilisation of cell membrane not only enhances drug efficiency, but also
      causes damage to cell organelles and alterations in cellular metabolism.

PMID- 8286212
TI  - An enzyme-linked immunosorbent assay for hypoxia marker binding in tumours.
AB  - An enzyme-linked immunosorbent assay (ELISA) has been developed for measuring the
      in vivo binding of a hexafluorinated 2-nitroimidazole (CCI-103F) in tumour tissue
      biopsies. The binding of CCI-103F is believed to reflect the presence of hypoxia
      in tumours. The ELISA provides a sensitive and convenient method of measuring CCI
      103F binding which does not require the injection of radioactive reagents. The
      ELISA is based on reagents prepared from synthetic antigens formed by the
      reductive activation and binding of CCI-103F to proteins in novel test tube
      experiments. Calibration of the ELISA involved comparing the ELISA with the
      radioactivity contained either in protein-CCI-103F adducts formed in vitro with
      tritiated CCI-103F or in tissues isolated from a tumour-bearing dog which had
      been injected with tritium-labelled CCI-103F. The two approaches to calibration
      are compared. The scope and limitation of the ELISA for measuring the binding of
      CCI-103F is discussed and an example of the application of the ELISA to measuring
      changes in tumour hypoxia in canine patients undergoing fractionated radiation
      therapy is presented.

PMID- 8286213
TI  - Production of immunoreactive polymorphonuclear leucocyte elastase in human breast
      cancer cells: possible role of polymorphonuclear leucocyte elastase in the
      progression of human breast cancer.
AB  - Breast cancer cells are known to express various proteolytic enzymes, which make
      them invasive and favour their dissemination to distant sites. However, it is
      unclear whether breast cancer cells have the ability to produce polymorphonuclear
      leucocyte elastase (PMN-E). We measured immunoreactive (ir) PMN-E content in the
      conditioned medium of two breast cancer cell lines, MCF-7 and ZR-75-1, and two
      normal breast epithelial cell lines, HBL-100 and Hs 578Bst, using a highly
      specific and sensitive enzyme immunoassay. Furthermore, ir-PMN-E content was
      determined in tissue extracts from 62 human breast cancers. ir-PMN-E content in
      the culture medium of MCF-7 cells and ZR-75-1 cells increased as a function of
      time, regardless of the presence or absence of oestradiol. On the other hand, no
      detectable ir-PMN-E was secreted into the culture medium of HBL-100 and Hs 578Bst
      cells. ir-PMN-E was detectable in 59 of 62 tissue extracts prepared from human
      breast cancers, the concentration ranging from 0.12 to 19.17 micrograms per 100
      mg of protein. When 62 breast cancer specimens were categorised into four groups
      in terms of clinical stage, ir-PMN-E content in breast cancer tissue was
      significantly higher in stage III (8.90 +/- 5.13 micrograms 100 mg-1 protein) and
      stage IV (12.19 +/- 5.44 micrograms 100 mg-1 protein) patients than in stage I
      (1.64 +/- 1.54 micrograms 100 mg-1 protein) and stage II (4.23 +/- 3.74
      micrograms 100 mg-1 protein) patients. Breast cancer patients with high levels of
      ir-PMN-E showed significantly shorter disease-free survival and overall survival
      than those with low levels of ir-PMN-E at the cut-off point of 8.99 micrograms
      100 mg-1 protein. In the multivariate analysis, ir-PMN-E content was found to be
      a significant prognostic factor for disease recurrence and death in human breast
      cancer.

PMID- 8286214
TI  - Biological effects of stable overexpression of aromatase in human hormone
      dependent breast cancer cells.
AB  - Aromatase is a key enzyme in the conversion of androstenedione and testosterone
      to oestrone and oestradiol. Intratumoral aromatase activity is expressed by
      around 70% of breast carcinomas, but it is not clear what effect this has on the
      tumour phenotype. To address this question we expressed human aromatase in
      hormone-dependent MCF-7 breast cancer cells. Clone Arom. 1 expressed aromatase at
      1,000 times the endogenous level in wild-type (WT) cells. Clone Arom. 2
      incorporated the expression construct but did not express aromatase at levels
      above WT. There was no morphological difference between the two clones and WT,
      all three cell lines expressed oestrogen receptor at equivalent levels, and all
      manifested a mitogenic response to oestradiol. In steroid-depleted medium Arom. 1
      cells showed significant growth enhancement over WT and Arom. 2, and this growth
      advantage was increased by exogenous androstenedione or testosterone. Both the
      enzyme activity and androgen-stimulated growth of Arom. 1 cells were completely
      reversible by aromatase inhibitor CGS 16949A. The Arom. 1 cell line may
      contribute to the development of an in vivo model of intratumoral aromatase, to
      study the biological significance of this phenomenon.

PMID- 8286215
TI  - Epidermal growth factor and transforming growth factor alpha characteristics of
      human oral carcinoma cell lines.
AB  - This study examined the expression of epidermal growth factor (EGF) cell-surface
      receptors, the response to exogenous ligand and the autocrine production of
      transforming growth factor alpha (TGF-alpha) in normal and carcinoma-derived
      human oral keratinocytes. One of eight malignant cell lines overexpressed EGF
      receptors, while the remainder expressed receptor numbers similar to normal
      cells. Exogenous EGF stimulated incorporation of tritiated thymidine in a dose
      dependent manner. In keratinocytes expressing normal numbers of EGF receptors,
      the cellular response to exogenous EGF correlated positively with total EGF
      receptor number. SCC-derived keratinocytes produced more TGF-alpha than normal
      cells. There was no statistical correlation between the autocrine production of
      TGF-alpha, EGF cell-surface receptor expression and cellular response to
      exogenous EGF. While the growth-stimulatory effects of exogenous TGF-alpha were
      inhibited by the addition of a neutralising antibody, the presence of this
      antibody in conditioned medium failed to produce a similar decrease in growth.
      The results indicate that overexpression of EGF receptors is not an invariable
      characteristic of human oral squamous carcinoma-derived cell lines. Further, the
      contribution of TGF-alpha to the growth of normal and carcinoma-derived human
      oral keratinocytes in vitro may be less significant than previously documented.

PMID- 8286216
TI  - Genome scanning of breast cancers by two-dimensional DNA typing.
AB  - We have recently used two-dimensional DNA typing to detect genetic alterations in
      breast tumours. This method, which is based on size separation in neutral gels
      and sequence separation in denaturing gradient gels followed by hybridisation
      analysis with mini- and microsatellite core probes, allows the simultaneous
      analysis of hundreds of allelic fragments in a very short time. Here we
      demonstrate the potency of this method for total genome scanning of the tumour
      genome by analysing a small series of breast cancers. Comparison of tumour and
      normal DNA from ten breast cancer patients, using two-dimensional DNA typing with
      four core probes, revealed a considerable number of genomic alterations. In
      contrast, with Southern blot analysis only a few alterations were observed using
      the same probes. Most of the changes observed (74%) were deletions (absence of
      spots in the tumour) while 20% corresponded to amplifications (spots of higher
      intensity in the tumour) and 5% were new spots (gains). About 10% of the genomic
      changes detected appeared to occur in the tumours of more than one patient.

PMID- 8286217
TI  - The role of apoptosis in cell killing by cisplatin: a flow cytometric study.
AB  - Cell killing of L1210 cells by cisplatin has been studied using flow cytometry
      and DNA gel electrophoresis. Ten hours after a supralethal dose of drug (100
      microM), extensive apoptosis was induced. Cells were also susceptible to the
      induction of apoptosis by nutritional deprivation, for example by incubation in
      arginine-deficient medium. After treatment in full medium with doses of drug in
      the range 1-10 microM, cells experienced a slow-down in S-phase transit followed
      by a G2 block. Cells either overcame the G2 block and continued to cycle or
      enlarged and eventually died. There was no evidence to suggest that cells dying
      from the G2 block underwent apoptosis. The data were consistent with a dual
      mechanism of cell death-higher doses of drug led to rapid death through
      apoptosis; lower doses led to death at later times resulting from failure to
      overcome a block in G2.

PMID- 8286218
TI  - Production of basement membrane components by a reconstructed epidermis cultured
      in the absence of serum and dermal factors.
AB  - A fully differentiated epithelium displaying features of human epidermis was
      obtained in vitro by culturing second-passage normal human keratinocytes for 14
      days in defined medium and on an inert polycarbonate filter substratum at the air
      liquid interface. Vertical sections stained for histology and indirect
      immunofluorescence studies showed that the 'basal' cells synthesize and secrete
      all major markers of hemidesmosomes and the lamina lucida. Components of the
      lamina densa are also expressed. Collagen VII is synthesized, but not secreted.
      Ultrastructural studies showed the presence of hemidesmosomes with major dense
      plaques and anchoring filaments, and a basement membrane-like structure was
      clearly identified. These results show that epidermal cells are able to produce
      hemidesmosomes and to secrete the major components of the dermo-epidermal
      junction in the absence of serum and dermal factors, suggesting that basement
      membrane synthesis and hemidesmosome assembly are not dependent on the presence
      of dermis.

PMID- 8286219
TI  - The relation between p53 mutation and p53 immunostaining in non-melanoma skin
      cancer.
AB  - Extensive study of the p53 gene has established its role as a tumour-suppressor
      gene, and the involvement of mutant p53 in a wide spectrum of human malignancy.
      Many mutations of p53 result in a protein product that is abnormally stable, so
      that it becomes readily detectable by immunocytochemistry. In contrast, under
      normal conditions, it has been considered that levels of wild-type p53 were too
      low to be detectable. Although positive immunocytochemistry has been used as a
      marker of mutation, recent evidence suggests that this assumption may not always
      be valid. We have carried out both PCR-sequencing of exons 5-8 of the p53 gene in
      20 basal cell carcinomas (BCC), and immunocytochemistry of these tumours with the
      anti-p53 antibody DO7. Twenty cases of Bowen's disease, in which we had
      previously documented mutations, were also immunostained. We report a low rate of
      p53 mutation in the BCCs we examined (2/20), and a discrepancy between tumours
      with positive immunostaining and those with mutation in both Bowen's disease and
      BCC. Of eight tumours in which we detected mutation, only four were
      immunopositive: of 19 immunopositive samples, only four showed detectable
      mutation. We discuss the implications of our results for the use of positive
      immunostaining in clinical diagnosis, and the involvement of p53 in skin
      carcinogenesis.

PMID- 8286220
TI  - Sunlight, keratotic skin lesions and skin cancer in renal transplant recipients.
AB  - In a retrospective follow-up study, 36 renal transplant recipients with, and 101
      without, skin cancer, who had received their first transplant before January 1981
      and who were still alive with a functioning graft on 1 August 1989, were assessed
      to determine the risk of non-melanoma skin cancer in relation to exposure to
      sunlight during childhood and adolescence. The contribution of the number of
      keratotic skin lesions to the skin cancer risk was also assessed. The estimated
      relative risks (odds ratios) of skin cancer in relation to exposure to sunlight
      and the presence of keratotic skin lesions were calculated by maximum likelihood
      estimation in a logistic model. The majority of skin cancers and keratotic skin
      lesions were confined to sun-exposed skin. After adjustment for possible
      confounding variables, the odds ratios of skin cancer for moderate and high
      cumulative life-time exposure to sunlight, respectively, compared with low
      exposure, were 2.4 (95% confidence interval [CI] 0.64-9.3) and 47.6 (95% CI 5.4
      418). Exposure to sunlight before the age of 30 contributed more to the risk of
      developing skin cancer later in life than exposure after the age of 30. No
      association was found between cumulative life-time exposure to sunlight and the
      number of keratotic skin lesions. Nevertheless, these lesions behaved as a strong
      independent risk factor in the development of skin cancer. The adjusted odds
      ratio of skin cancer for 50-99 lesions compared with < 50 lesions was 4.5 (95% CI
      1.1-18.2); the adjusted odds ratio for > or = 100 lesions compared with < 50
      lesions was 20.8 (95% CI 5.3-81.7).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286221
TI  - Anti-HLA antibodies in pemphigoid gestationis (herpes gestationis).
AB  - Pemphigoid gestationis (PG; herpes gestationis) is a rare autoimmune disease
      associated with pregnancy, currently defined by the presence of complement
      deposition along the cutaneous basement membrane zone. It is known to be
      associated with HLA-DR3 and DR4, and an increase in anti-HLA antibodies in those
      with a history of PG has been reported. We have studied 39 patients with an
      immunofluorescence-confirmed diagnosis of PG for the presence and specificity of
      anti-HLA antibodies. Anti-HLA antibodies were found in all 39 patients.
      Specificity was against class I antigens in 98% (controls 10%; P < 0.001) and
      class II antigens in 25% (controls 8.5%; P < 0.001). Almost all anti-HLA
      antibodies were cytotoxic. The universal presence of anti-HLA antibodies in PG
      suggests that they may develop coincidently with antibasement membrane
      antibodies, and may reflect a common immunological event.

PMID- 8286222
TI  - A clinical classification and grading system of the cutaneous changes in
      onchocerciasis.
AB  - Although onchocerciasis is one of the most important diseases of the skin and eye
      in the tropical world, to date there has been no formal consensus regarding the
      description and terminology of skin lesions. Furthermore, the contribution of
      cutaneous pathology to the morbidity and socio-economic effects of the disease
      has been largely neglected. We present a clinical classification and grading
      system for recording the cutaneous changes of onchocerciasis, and propose that
      this system be used as a standard method of description to convey clinical
      information between workers in all endemic areas to assist local and comparative
      research.

PMID- 8286223
TI  - Venous leg ulcers: an analysis of underlying venous disease.
AB  - Patients with venous leg ulcers have a readily recognized clinical syndrome of
      shallow ulcers, oedema, leg pain, venous ankle blush, lipodermatosclerosis,
      varicose veins, hyperpigmentation, and atrophie blanche, and they are assumed to
      have venous abnormalities. We examined 43 patients with venous leg ulcers, and
      compared those with obvious venous abnormalities (defined as historical or
      clinical evidence of deep venous thrombosis or varicose veins) with those with
      presumed venous abnormalities (defined as lacking any such evidence), to see if
      they presented with different clinical features. We found that both groups had
      similar clinical features, with the exception that lipodermatosclerosis was
      present more frequently in those patients with obvious venous abnormalities (94
      vs. 36%, P < 0.001). Most patients with presumed venous abnormalities had
      musculoskeletal conditions which might cause calf pump dysfunction (91%). Using
      air plethysmography, we were unable to confirm that all patients with presumed
      venous abnormalities did have intrinsic venous abnormalities. We propose that
      ulcers occurring in this clinical syndrome be designated as calf pump dysfunction
      ulcers (CPD ulcers), rather than venous ulcers.

PMID- 8286224
TI  - Immunological evaluation of erythema nodosum in tularaemia.
AB  - During two tularaemia outbreaks in the Bursa region of Turkey in 1991, a total of
      98 patients were diagnosed and evaluated. Thirteen of these patients had erythema
      nodosum, which is accepted as a secondary skin manifestation. The patients with
      erythema nodosum, 21 patients without any skin lesions, and 20 healthy controls
      were studied. Comparable elevations of levels of IgG, IgA, and IgM were detected
      in the two tularaemia groups. There was no difference in complement C3c and C4
      levels between the groups. All of the patients with erythema nodosum had elevated
      circulating immune complex (CIC) levels, when compared with the patients without
      skin lesions and the control group. The acute phase response (C-reactive protein
      [CRP] and erythrocyte sedimentation rate [ESR]) of the erythema nodosum group was
      significantly higher than the patients with normal skin, and healthy controls (P
      < 0.001). Serum transferrin levels were significantly decreased in both of the
      tularaemia groups (P < 0.001). Serum soluble interleukin-2 receptor levels (SIL
      2R) were significantly elevated in both tularaemia groups (P < 0.001), and the
      elevation was more marked in the erythema nodosum group (P < 0.05).
      Histopathological evaluation of biopsies from two patients with erythema nodosum
      showed dermal oedema, a perivascular lymphocytic infiltrate, and panniculitis. No
      immunoglobulin or complement deposits were detected on immunofluorescence.
      Erythema nodosum in the course of tularaemia is associated with many
      immunological changes, although it is not clear whether these findings are
      related to the increased tissue response, or whether they play a role in the
      pathogenesis of the erythema nodosum.

PMID- 8286225
TI  - Reciprocity between tissue calmodulin and cAMP levels: modulation by excess zinc.
AB  - Signal transduction of many intracellular events is initiated by a minute influx
      of calcium ions into the cells, resulting in the formation of calcium-calmodulin
      complex and cAMP. Because zinc appears to have an inhibitory effect on a number
      of tissue reactions, it is postulated that this occurs through modulation of
      intracellular calcium influx. To test the hypothesis that the inhibitory effects
      of zinc are mediated through the calcium-calmodulin-cAMP pathway, zinc was
      administered by various routes to five groups of nude mice (control,
      intragastric, intraperitoneal, intradermal and oral groups), and calmodulin and
      cAMP concentrations were measured in the cytosol of epidermal cells. Calmodulin
      levels decreased significantly in the groups given intraperitoneal zinc (P <
      0.025) and intradermal zinc (P < 0.001) injections. Significant elevations of
      cAMP levels were noted with intradermal zinc (P < 0.025). Overall, the
      relationship between calmodulin and cAMP appeared to be inversely logarithmic,
      with the lowest calmodulin levels associated with the highest cAMP
      concentrations. In addition, there was a significant trend towards a smaller
      calmodulin/cAMP ratio in all zinc-treated groups, except the mice fed dietary
      zinc. These results appear to correlate with tissue zinc levels obtained with
      these various forms of zinc administration. Our results therefore indicate that
      there is a reciprocity between epidermal calmodulin and cAMP levels, which may be
      modulated by external factors such as zinc.

PMID- 8286226
TI  - Ibuprofen epidermal levels after topical application in vitro: effect of
      formulation, application time, dose variation and occlusion.
AB  - The influence of vehicle (two oil-in-water emulsions and two gels, each
      containing 10% or 5% ibuprofen) application time (0.5, 1, 2 h), applied dose
      (1.5, 3, 6, 12 mg/cm2), time (24 h after an 0.5 h application time), and
      occlusion on the epidermal concentration of ibuprofen was investigated. The drug
      concentration in the epidermis was measured by HPLC. All results were expressed
      as microgram drug/mg epidermal protein. The application time had no influence on
      the epidermal drug concentration, whereas the two gel formulations produced
      concentrations approximately twice those obtained with the emulsions. A
      significant positive correlation was found between the applied dose and the
      epidermal concentration for each formulation. After 24 h the amount of drug
      remaining in the epidermis was low (reduced by factors of 10-20). Occlusion
      produced higher concentrations, but only with the 2-h application time. The
      methods are reliable, and useful in ranking vehicles according to their ability
      to release ibuprofen into the epidermis. Future investigations should explore the
      relationship between epidermal concentration and anti-inflammatory efficacy in
      vivo.

PMID- 8286227
TI  - Isotretinoin for acne vulgaris--10 years later: a safe and successful treatment.
AB  - The purpose of this study was to assess the long-term benefit of isotretinoin in
      otherwise therapy-resistant acne. We also assessed risk factors which might
      influence the long-term outcome. We studied 88 patients (mean age 20.8 years),
      most of whom had suffered from acne for many years (mean 7.4 years). They
      received isotretinoin in an initial dose of 0.5 or 1.0 mg/kg/day. The dose was
      subsequently adjusted according to response and side-effects. Most patients only
      required 4 months' therapy to produce at least 85% clinical improvement. The
      patients were seen up to 10 years post-therapy (mean 9 years). Sixty-one patients
      were still virtually clear of disease. Of the others, 16% required further
      treatment with conventional antibiotics and 23% required a second course of
      isotretinoin. Of those who relapsed, 96% did so within 3 years of stopping
      therapy. The patients' age, sex, and duration of acne did not influence outcome.
      However, in patients with predominantly truncal acne, especially when severe,
      there was an increased incidence of relapse. Sebum excretion is known to
      correlate with acne severity, but the long-term degree of sebum suppression was
      found not to be related to relapse. The dose schedule, in particular cumulative
      dose, was an important factor in determining relapse rate. Those patients who
      received 0.5 mg/kg daily, or a cumulative dose of < 120 mg/kg, had a
      significantly higher relapse rate than patients receiving a larger dose. We did
      not elicit any long-term systemic or biochemical side-effects. We conclude that
      isotretinoin is a safe and effective therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286228
TI  - Isotretinoin for the treatment of acne vulgaris: which factors may predict the
      need for more than one course?
AB  - We investigated 299 patients treated 5-10 years ago with isotretinoin, and
      followed them for 5 years post-treatment. Of the 299 patients 22.7% required
      repeat courses of treatment; 17% had two courses, 5% had three courses and 1% had
      4-5 courses. Response to further treatment was predictably successful, was not
      associated with any additional adverse reactions, and produced no persistent side
      effects. Factors contributing to the need for further courses of treatment
      included lower dose regimens (0.1 and 0.5 mg/kg), the presence of severe acne,
      being a female over the age of 25 at the onset of therapy, and having a prolonged
      history of acne.

PMID- 8286229
TI  - The effect of topical tretinoin on photodamaged facial skin: the Thai experience.
AB  - Because of the climate in Bangkok, Thailand, a prematurely aged appearance is
      common in adults beyond 40 years of age. Sixty-one Thai people with moderate to
      severe signs of dermatoheliosis applied 0.05% tretinoin cream to the face once
      daily for 6-12 months. Four-mm punch biopsies were obtained from the cheeks
      before and after treatment. These were formalin-fixed and evaluated
      histochemically. A surprising degree of photodamage was noted histologically in
      these dark-skinned people. After 6 months of tretinoin, epidermal atypia and
      atrophy were largely corrected. There was a great diminution in the density of
      melanin granules within keratinocytes and corneocytes. Tretinoin did not
      significantly affect the dermal matrix after 6 months. However, after 12 months,
      a thin band of new collagen was deposited beneath the epidermis, accompanied by
      the formation of new vessels (angiogenesis). By global assessment, after 12
      months most subjects experienced at least moderate improvement in appearance,
      especially with regard to hyperpigmented spots and fine wrinkles.

PMID- 8286230
TI  - Efficacy of topical 5% liquor carbonis detergens vs. its emollient base in the
      treatment of psoriasis.
AB  - Tar has been a mainstay in the treatment of psoriasis for centuries, but despite
      its widespread use, there is little evidence supporting its clinical efficacy
      without the combined use of ultraviolet radiation. The purpose of this study was
      to compare psoriasis improvement rates in patients using 5% liquor carbonis
      detergens (LCD) in an emollient base with the emollient base alone. Eighteen
      patients completed a randomized, bilaterally controlled, double-blind study.
      Emollient-treated plaques showed a mean improvement of 35.3% by 4 weeks of
      treatment, and LCD therapy produced a mean improvement of 48.7%, a difference
      which was statistically significant.

PMID- 8286231
TI  - Lupus vulgaris confirmed by polymerase-chain reaction.
AB  - We report a case of lupus vulgaris with typical clinical and histological
      findings. Mycobacterium tuberculosis was not only identified by a conventional
      culture technique, but also by a recently established system which has been
      designed to detect mycobacterial DNA in formalin-fixed, paraffin-embedded tissue
      by polymerase-chain reaction (PCR). Because results can be obtained within days,
      the PCR-based technique may markedly facilitate the diagnosis of skin
      tuberculosis.

PMID- 8286232
TI  - Reticulate purpura, cryoglobulinaemia and livedo reticularis.
AB  - Two patients with type I cryoglobulinaemia are described, both of whom presented
      with purpura in a reticulate distribution on the legs, resembling the pattern of
      physiological livedo. It appeared that increased cooling due to sluggish blood
      flow in areas of the skin corresponding to the blue areas of physiological livedo
      may have caused the localization of cryoprecipitate at these sites. To
      investigate the pathogenesis of the net-like pattern of purpura, three subjects
      with physiological livedo reticularis of the thighs were studied with a laser
      Doppler velocimeter. In two subjects, mean blood flux in the blue areas was 21%
      (P < 0.01) and 26% (P < 0.02) lower than in adjacent white areas, whereas in the
      third there was no significant difference. The cutaneous features of
      cryoglobulinaemia, and the mechanism of the reticulate purpura in this condition,
      are discussed.

PMID- 8286233
TI  - Inflammatory breast carcinoma (carcinoma erysipeloides): an easily overlooked
      diagnosis.
AB  - A 70-year-old woman developed erythema and induration of the right chest wall,
      and swelling of her right arm. The provisional diagnosis was deep venous
      thrombosis and/or cellulitis of the right arm. Skin biopsy showed a poorly
      differentiated adenocarcinoma within lymphatic vessels, and immunohistochemical
      staining revealed this to be of breast origin. Inflammatory carcinoma or
      carcinoma erysipeloides represents < 1% of all cases of breast carcinoma. Our
      case illustrates the importance of considering this entity in the differential
      diagnosis of unilateral chest wall erythema and induration.

PMID- 8286234
TI  - Melanoma erysipeloides: inflammatory metastatic melanoma of the skin.
AB  - We report a case of diffuse infiltration of the skin of the chest wall with
      metastatic melanoma. This developed as a direct extension from right axillary
      lymph nodes. Histology and immunohistochemistry showed invasion of dermal
      lymphatics with melanoma cells.

PMID- 8286235
TI  - Adult Kawasaki syndrome.

PMID- 8286236
TI  - Acquired vulval lymphangiomata mimicking genital warts.
AB  - Acquired cutaneous lymphangiomata are characterized clinically by the presence of
      a circumscribed eruption of thin-walled, translucent vesicles. However,
      epithelial changes and tissue organization may occasionally give rise to firmer
      nodules or even warty lesions. When these arise on the vulva, diagnostic
      difficulties may ensue. We report two patients in whom vulval lymphangiomata
      resulting from treatment for cervical neoplasia were mistaken for viral warts.

PMID- 8286237
TI  - Squamous cell carcinoma arising within congenital lymphangioma circumscriptum.

PMID- 8286238
TI  - Reticular erythematous mucinosis syndrome and a monoclonal IgG kappa paraprotein-
      is there an association?

PMID- 8286239
TI  - Aquagenic pruritus and acute lymphoblastic leukaemia.

PMID- 8286240
TI  - Assessment of severity score in patients with psoriasis.

PMID- 8286241
TI  - An efficient method for isolation of hair papillae and follicle epithelium from
      human scalp specimens.

PMID- 8286242
TI  - Clearance of confluent and reticulate papillomatosis of Gougerot and Carteaud
      with minocycline.

PMID- 8286243
TI  - Pityriasis lichenoides chronica resolving after tonsillectomy.

PMID- 8286244
TI  - Acute generalized exanthematous pustulosis due to diltiazem.

PMID- 8286245
TI  - Fordyce spots responding to isotretinoin therapy.

PMID- 8286246
TI  - Undergraduate teaching in dermatology and general practice.

PMID- 8286247
TI  - Immunophenotypic studies in cutaneous T-cell lymphomas: clinical implications.
AB  - Examination of biopsies from 62 patients with, or suspected of having cutaneous T
      cell lymphoma (CTCL) revealed 24 cases in which the neoplastic cells expressed
      aberrant or suppressor T-cell phenotypes. The clinical records of these patients
      were reviewed in an attempt to establish whether recognition of these phenotypes
      has any clinical implications. Twelve patients had mycosis fungoides (MF) with
      plaques (n = 4) or tumours (n = 8), four had Sezary syndrome, and eight had large
      cell lymphomas of pleomorphic (n = 6) or anaplastic subtype (n = 2). Most of the
      large-cell lymphomas behaved aggressively, as might have been expected from their
      cytological appearance. Aggressive courses were also seen in Sezary syndrome, and
      in tumour lesions of MF, whereas the behaviour in cases of plaque lesions was
      indolent. Again, this might have been anticipated from the clinical staging and
      routine histological examination. It is suggested that the expression of aberrant
      or suppressor T-cell phenotypes in CTCL is not of independent prognostic
      significance, but that the stage and histology are more important. This issue is
      an important topic for a prospective analysis.

PMID- 8286248
TI  - Immunophenotyping on simultaneously occurring plaques and tumours in mycosis
      fungoides and Sezary syndrome.
AB  - Skin biopsy specimens from 15 patients with mycosis fungoides and Sezary
      syndrome, with simultaneously occurring plaques and tumours, were examined to
      assess phenotypic deviation. We focused on immunophenotypic differences between
      the two types of lesions with respect to the T-cell markers CD2, CD3, CD4, CD5
      and CD8. In six patients (40%) loss of one or more T-cell markers occurred in at
      least one of the lesions. Three of the patients studied (20%) showed a difference
      in immunophenotype between plaques and tumours, with an additional loss of one of
      the T-cell markers in the tumours (respectively, CD5, CD2 and CD4). All three of
      these patients showed a larger number of blast cells in the tumour compared with
      the plaque. No correlation between this loss of antigenicity and the prognosis
      was observed. The results of this study show that different immunophenotypes can
      occur simultaneously in an individual patient. Furthermore, we were able to
      confirm a relationship between the number of intraepidermal CD1+ cells in plaque
      lesions and the prognosis.

PMID- 8286249
TI  - Patients with psoriasis often have increased serum levels of IgA antibodies to
      gliadin.
AB  - It was recently observed that in six patients with psoriasis and one with
      palmoplantar pustulosis, with newly discovered gluten intolerance, a gluten-free
      diet had a remarkable effect on the skin lesions. This prompted us to undertake a
      screening investigation to discover whether increased levels of serum antibodies
      to gliadin are more common in patients with psoriasis than in healthy persons.
      IgA and IgG antibodies to gliadin (IgA AGA and IgG AGA) were quantified by a
      micro-ELISA method. Out of 302 patients with psoriasis, 16% (18 females, 31
      males) showed serum IgA AGA levels above the 90th percentile value (51 u/ml) of
      the reference group. This tendency was even more marked when the proportion of
      patients with values > 70 u/ml was compared with the corresponding proportion of
      99 reference subjects. Thus, 3% of the reference subjects but 7.9% of the
      patients had values > 70 u/ml. The corresponding figures for men were 1.6% and
      8.9%, respectively. Men with psoriasis had a significantly higher mean IgA AGA
      than the male reference group. The means based on logarithmic values of the
      individual IgA AGA values were significantly higher in the psoriatic groups than
      in the reference groups. Although the mean level of IgG AGA was not increased in
      the psoriasis group, there was a correlation between the values for IgA AGA and
      IgG AGA. The serum concentrations of IgG, IgA and IgM were also measured. In the
      male patients, the mean IgA value was significantly increased. Women in whom IgA
      AGA was elevated also showed a significantly increased mean IgA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8286250
TI  - A calmodulin-like protein as an extracellular mitogen for the keratinocyte.
AB  - This study investigated the importance of extracellular calmodulin to the
      proliferation of the keratinocyte. Normal keratinocytes in culture produced a
      calmodulin-like protein in their culture media, the level of which increased
      abruptly and transiently during their growth. This protein was calmodulin-like,
      in that it specifically bound to a calmodulin affinity column, exhibited
      calmodulin-like immunoreactivity in both an ELISA and on immunoblots when
      immunostained with a monoclonal antibody against calmodulin, had an apparent M(r)
      between 18,000 and 20,000, and stimulated activity in a calmodulin-dependent
      phosphodiesterase enzyme assay. Addition of exogenous pure calmodulin was of no
      further mitogenic benefit to the keratinocytes, and slightly reduced
      proliferation under the culture conditions used. However, addition of either a
      neutralizing antibody to calmodulin, or W7-agarose, to the culture media of
      proliferating cells markedly inhibited their proliferation. Accordingly, a
      calmodulin-like protein was found to satisfy all but one of the criteria for its
      action as an autocrine growth factor for the keratinocyte. We propose that the
      lack of mitogenic response to calmodulin in vitro is due to the cell meeting its
      own requirement for extracellular calmodulin.

PMID- 8286251
TI  - Are pigmented lesion clinics worthwhile?
AB  - To assess the effect of a pigmented lesion clinic on referral patterns and
      thickness of melanoma at presentation, we have compared data from the centralized
      pathology services of the adjacent health authorities of Wandsworth, and Merton
      and Sutton. Both districts were the subject of a CRC public awareness campaign in
      1987, but only Wandsworth is served by a pigmented lesion clinic. All patients
      presenting with malignant melanoma were included; from 1981 to 1990 for
      Wandsworth, and from 1984 to 1990 for Merton and Sutton. The Breslow thickness
      and clinic source of all melanomas was documented. Approximately equal numbers of
      melanomas were seen in the two districts, with no obvious difference in the
      numbers of thin (< 1.5 mm thick) 'good prognosis' tumours. Both districts saw an
      increase in the total number of tumours, and the number of thin tumours, after
      the CRC publicity campaign. However, there was considerable cross-boundary
      referral to the pigmented lesion clinic in Wandsworth, with 60% of all melanomas
      coming from outside the district. The presence of a pigmented lesion clinic
      within a given district confers no obvious benefit with regard to the number of
      thin, 'good prognosis' melanomas being seen as a whole, but the cross-boundary
      referral pattern suggests that it fulfils a demand from both general
      practitioners (GPs) and patients, and it does provide a centralized source for
      the collection of much-needed data.

PMID- 8286252
TI  - Dermatitis herpetiformis and established coeliac disease.
AB  - Fifteen (5.3%) of 282 patients with dermatitis herpetiformis (DH) were diagnosed
      as suffering from coeliac disease before the onset of their DH. This group showed
      a female preponderance, and a later than usual onset of DH. The mean age at which
      DH developed was 40.0 years, and there was a mean interval of 13.2 years between
      the two diagnoses. Seven patients had stopped their gluten-free diet, and a
      further four were poor compliers. Persistent gluten ingestion in coeliacs with a
      specific genetic predisposition may result in the development of DH.

PMID- 8286253
TI  - Folliculitis in Down's syndrome.
AB  - Twenty-two male and 20 female adults with Down's syndrome were examined. Ten of
      the men and two of the women had a follicular rash consistent with Malassezia
      folliculitis. Oral itraconazole treatment produced a significant improvement in
      the rash, accompanied by a decrease in the skin Malassezia count. Clinical
      relapse occurred when therapy was discontinued, and was accompanied by return of
      the Malassezia yeasts.

PMID- 8286254
TI  - A device for phototesting patients before PUVA therapy.
AB  - A device is described and validated for rapid and easy phototesting of patients
      at the start of a course of PUVA therapy. The phototesting template consists of
      metal foil with four apertures of 10 mm diameter, mounted in pliable
      polyurethane. One aperture is open, and the other three each incorporate a grid
      of hexagonal holes of differing size which attenuate the radiation, resulting in
      relative intensities at the skin surface of 1, 2, 4 and 8. Thus, a single
      exposure through the foil of, for example, 8 J/cm2, would allow the minimal
      phototoxic dose to be determined as either 1, 2, 4, 8, or > 8 J/cm2. The device
      was validated by comparison with a metal foil with four open apertures, but
      otherwise identical construction, in which the dose was controlled by varying the
      exposure time. In 11 subjects, tested with one device on each arm, the minimal
      phototoxic dose, judged visually, was identical. Reflectance measurements of
      erythema at each of the test sites showed no systematic difference between the
      two methods. The device has no moving parts, requires no source of electrical
      power, will not change its optical transmission with age, and is robust and easy
      to use. It should, therefore, allow much wider application of the useful
      technique of minimal phototoxic dose determination before PUVA therapy.

PMID- 8286255
TI  - Isotretinoin therapy for acne vulgaris: a re-evaluation of the need for
      measurements of plasma lipids and liver function tests.
AB  - A retrospective analysis of patients receiving isotretinoin for acne was
      performed, in order to determine the necessity for routine testing of lipid
      profiles and liver function tests during therapy. Data were analysed from 209
      individuals, 113 (69 males, 44 females) of whom had been treated with 1
      mg/kg/day, and 96 (67 males, 29 females) with 0.5 mg/kg/day. There were no
      significant changes in any of the tests of liver function. There were significant
      elevations in both plasma cholesterol and triglycerides at 8 and 16 weeks (P <
      0.01) for both dose schedules, which were significant in both male and female
      subjects (P < 0.001). All the individuals with elevated cholesterol (> 6.5
      mmol/l) at 16 weeks had elevated cholesterol at the onset of therapy.
      Triglyceride concentrations were elevated at 8 weeks, but there was no further
      increase thereafter. It was not possible to predict which subjects would become
      hypertriglyceridaemic from pretreatment lipid estimations. In conclusion, there
      appears to be little evidence to support the previously recommended regular
      biochemical monitoring of liver function and lipid profiles in patients who are
      treated with isotretinoin for 16 weeks. It would appear prudent to ensure that
      there is neither liver disease nor hyperlipidaemia prior to the onset of therapy,
      and to determine the triglyceride response to therapy on one occasion after 4
      weeks' treatment. This change in patient management should result in considerable
      savings both in patient time and in blood collection and analysis.

PMID- 8286256
TI  - A comparison of narrow band phototherapy (TL-01) and photochemotherapy (PUVA) in
      the management of polymorphic light eruption.
AB  - Twenty-five patients suffering from severe polymorphic light eruption (PLE) were
      randomized to either photochemotherapy (PUVA) or narrow-band phototherapy (TL-01
      UVB) treatment in early spring; patients receiving UVB were given placebo tablets
      to achieve a matching therapy procedure. During the 4 months following treatment,
      patient exposure to solar UVB was monitored with polysulphone badges. PLE
      occurrence, severity, and restriction of outdoor activity were recorded, using
      weekly diary-sheets. Analysis of covariance on this data, using the logarithm of
      UVB exposure as the explanatory variable, showed no significant differences
      between the treatments. TL-01 UVB is an effective alternative to PUVA in the
      management of PLE.

PMID- 8286257
TI  - Highly purified omega-3-polyunsaturated fatty acids for topical treatment of
      psoriasis. Results of a double-blind, placebo-controlled multicentre study.
AB  - We report the results of a multicentre, double-blind, placebo-controlled study of
      topical therapy with omega-3-polyunsaturated fatty acids (omega-3-PUFA) in 52
      patients suffering from moderate plaque-type psoriasis. In each patient, two
      similar stable psoriatic plaques served as indicator lesions for the study. One
      indicator lesion was randomly assigned to treatment with topical preparations of
      highly purified omega-3-PUFA in one of two concentrations (1 or 10%), and the
      other was treated with placebo. Efficacy assessment was based on changes in local
      psoriasis severity index, area involved, erythema, desquamation, induration and
      pruritus. After 8 weeks of treatment, all indicator lesions had improved
      significantly, compared with baseline. However, no statistically or clinically
      relevant differences between the omega-3-PUFA-treated and the placebo-treated
      lesions were found. Therapy was well tolerated and, apart from one patient who
      developed perilesional eczema, no clinically relevant adverse events occurred. In
      conclusion, topical omega-3-PUFA were not effective in a randomized, placebo
      controlled, double-blind setting. Results of non-blind trials should be (re
      )considered with caution.

PMID- 8286258
TI  - Superficial granulomatous pyoderma. A report of two cases.
AB  - We report two cases of superficial granulomatous pyoderma (SGP). Unlike classical
      pyoderma gangrenosum this variant is characterized by a benign course,
      superficial ulceration and a granulomatous infiltrate. Although our cases share
      the typical features of SGP, they are noteworthy in that one had the disease for
      18 years, and the other had concomitant sarcoidosis.

PMID- 8286259
TI  - Rothmund-Thomson syndrome and osteosarcoma.
AB  - A 10-year-old girl with Rothmund-Thomson syndrome developed a fibular
      osteosarcoma. Standard chemotherapy produced intolerable toxicity, necessitating
      a modification of therapy. Initial DNA repair studies on skin fibroblasts were
      abnormal, but repeat studies failed to reproduce the defects.

PMID- 8286260
TI  - Cutaneous 'ringworm' lesions of Scopulariopsis brevicaulis.
AB  - Scopulariopsis brevicaulis is a saprophytic fungus which is occasionally isolated
      as an apparent cause of toenail fungal infection, and which rarely has been
      reported as a cause of deep fungal granuloma. We report a case of skin infection
      with this organism, which was proved by culture of a pure isolate. The skin
      lesions had an annular ringworm appearance with pustules, they occurred initially
      at a site of minor injury, and they responded to treatment with terbinafine and
      itraconazole.

PMID- 8286261
TI  - Dermatophyte pseudomycetoma: a case report.
AB  - A 25-year-old man presented with several prominent subcutaneous masses in the
      occipital region of the scalp. He had a long history of tinea capitis and tinea
      corporis infection. Histopathology of the occipital lesions showed mycelial
      aggregates in the deep dermis and subcutis. Cultures of the excised material and
      superficial scales grew a fungus identified as Microsporum ferrugineum. We
      propose the term 'dermatophyte pseudomycetoma' to describe this distinctive
      mycosis.

PMID- 8286262
TI  - Electron-beam therapy in Arndt-Gottron's scleromyxoedema.
AB  - We report a patient with Arndt-Gottron's scleromyxoedema whose skin lesions
      responded to electron-beam therapy. This treatment appears to be effective in
      improving the cutaneous signs and functional impairment of this disease.

PMID- 8286263
TI  - Systemic sclerosis terminating as systemic necrotizing angiitis.
AB  - We report a 57-year-old woman with systemic sclerosis (SSc) who died suddenly,
      following a haemoptysis. At post-mortem, systemic necrotizing angiitis of small
      vessels was observed in several organs. Necrotizing angiitis has been reported as
      a rare complication of systemic sclerosis, and is usually lethal.

PMID- 8286265
TI  - Pemphigoid nodularis.

PMID- 8286264
TI  - Epidermal antigens and complement-binding anti-intercellular antibodies in
      pemphigus vegetans, Hallopeau type.
AB  - The serum of a 34-year-old woman with the Hallopeau type of pemphigus vegetans
      (PVg) contained antibodies against a 130-kDa polypeptide in human epidermal
      lysates, as revealed by Western blot analysis. The serum strongly fixed
      complement in vitro, and the PVg lesional skin contained a predominance of
      complement-fixing IgG2 and IgG4. Although the antigens reactive with sera from
      PVg and pemphigus vulgaris were the same, strong fixation of complement by PVg
      antibodies, due to the presence of complement-dependent IgG subclasses, and
      subsequent in situ activation of complement, might explain the marked
      infiltration of neutrophils and eosinophils in PVg.

PMID- 8286266
TI  - Splenectomy followed by local injections of interferon-alpha is effective for
      treating cutaneous-type adult T-cell leukaemia/lymphoma.

PMID- 8286267
TI  - Lichen sclerosus et atrophicus confined to the areolae.

PMID- 8286268
TI  - Smoking, drinking and psoriasis.

PMID- 8286269
TI  - Response of nail psoriasis to cyclosporin.

PMID- 8286270
TI  - Cyclosporin A does not affect epidermal proliferation following standardized
      injury.

PMID- 8286271
TI  - The efficacy of topical cyclosporin in the management of desquamative gingivitis
      due to lichen planus.

PMID- 8286272
TI  - An update on the peripheral pseudoaneurysm.
AB  - A false aneurysm, or pseudoaneurysm, is a hematoma that occurs after injury of
      all layers of the arterial wall and that may occur secondary to trauma or to
      infection or as a complication of arterial bypass reconstruction. The presence of
      a pulsatile mass is usually the initial finding on physical examination that
      leads to more definitive testing and diagnosis. Treatment traditionally has been
      surgical repair. Recently, observation of stable false aneurysms and ultrasound
      guided compression have proved to be effective and less invasive in a select
      group of patients. This article focuses on the incidence, causes, diagnosis, and
      various treatment modalities used today. The role of the nurse in caring for
      these patients is also addressed.

PMID- 8286273
TI  - Three methods of taking the brachial systolic pressure to measure the
      ankle/brachial index: which one is best?
AB  - This study was designed to determine which method of measuring the brachial
      systolic blood pressure is most accurate when determining the ankle/brachial
      index (ABI). The accuracy of the stethoscope diaphragm was compared with the
      accuracy of the stethoscope bell and Doppler methods in measuring the brachial
      systolic pressure. These pressures were used in the calculation of the ABI, and
      then the ABI was compared by method and time since surgery. The sample consisted
      of 31 subjects who had peripheral arterial bypass surgery. The findings of this
      study indicate that there is no significant difference in the ABI when the
      brachial systolic blood pressure is measured by any of the three methods. A
      difference was found between the right-arm and left-arm brachial systolic
      pressures in many of the patients, and this would make a difference in the
      calculation of the ABI.

PMID- 8286274
TI  - Reperfusion injury.
AB  - Reperfusion injury occurs after flow is restored to an ischemic area in an effort
      to salvage limbs and prevent amputation. Skeletal muscle damage occurs during
      ischemia as well as during reperfusion. Literature review supports the theory
      that reperfusion of the ischemic area may cause a chain of events that results in
      irreversible necrosis. Neutrophils, calcium, and oxygen free radicals appear to
      play a significant role in the cellular injury during reperfusion. Free radical
      scavengers administered at the appropriate time may prevent injury. Nurses play a
      significant role in identifying signs of reperfusion injury.

PMID- 8286275
TI  - Interruption of the inferior vena cava for venous thromboembolic disease.
AB  - The indications for interruption of the inferior vena cava include recurrent
      pulmonary emboli in the presence of adequate anticoagulation, contraindication to
      anticoagulation, contraindication to thrombolytic therapy, or the presence of
      other conditions demanding prophylaxis for pulmonary emboli. Interruption of the
      inferior vena cava by filter insertion has increased in recent years. The most
      commonly used filter is the Greenfield filter. This article reviews indications,
      insertion procedures, complications, and the nursing implications related to
      filter insertion via the inferior vena cava.

PMID- 8286276
TI  - President's address: the secret's out.

PMID- 8286277
TI  - Selecting a treadmill for home use.

PMID- 8286278
TI  - Popliteal artery entrapment.

PMID- 8286279
TI  - Management of patients undergoing vascular surgery who are receiving epidural
      analgesia.
AB  - Epidural analgesia affords new opportunities for pain management in the acute and
      chronic arenas for patients undergoing vascular surgery. Effective and safe
      management of the patient receiving epidural analgesia requires careful
      integration of the skills and knowledge of the health care providers. Vascular
      surgeons in this institution use epidural analgesia almost exclusively in
      postoperative management of the patient undergoing vascular surgery, resulting in
      consistent pain relief with reduced narcotic requirements and earlier
      mobilization. Recognized complications are associated with epidural analgesia.
      Thus development of standardized nursing care plans to ensure safe and
      appropriate care of patients is imperative. Monitoring specific quality
      indicators ensures safe delivery of epidural analgesia and evaluates the
      effectiveness of the pain management program.

PMID- 8286280
TI  - The role of duplex and color Doppler imaging in the operating room.
AB  - For years vascular surgeons have used objective methods in the operating room to
      assess the technical quality of vascular procedures. Black and white (duplex) and
      color Doppler imaging are critical to the preoperative work-up and postoperative
      follow-up of many patients. With advancing technology it is possible to adapt
      these imaging techniques for use in the operating room as well. Anatomic and
      hemodynamic results can therefore be ascertained before the patient leaves the
      operating room. Over the past 31 months, vascular surgeons at St. John's Mercy
      Medical Center (SJMMC) have regularly used duplex and color Doppler imaging in
      the operating room after carotid thromboendarterectomy and renal artery bypass. A
      peripheral vascular laboratory nurse is called to the operating room and brings
      the imaging equipment and videotape recorder. The imaging transducer is draped
      with a sterile sheath and positioned directly on the vessel. Longitudinal and
      transverse views are obtained; the presence of intimal flap or turbulent color
      flow is noted. Sound spectral analysis and peak systolic velocity are obtained in
      centimeters per second (cm/sec) at various locations proximal and distal to the
      arteriotomy and within the graft or endarterectomized segment. Results are
      classified as normal or abnormal. Abnormal findings are further classified as
      accepted or warranting reexploration. Of 81 carotid scans, 55 (67%) were normal
      and 26 (33%) abnormal by imaging. Of 28 abnormal sites, 14 (17%) were reexplored
      and the abnormality repaired. The other 14 abnormalities were accepted. Duplex
      and color Doppler imaging have proved helpful to surgeons in assessing technical
      results before the patient leaves the operating room.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8286281
TI  - Research: conception to completion.
AB  - A lack of theory-based nursing research exists in the area of vascular disease.
      Nursing research is critical to evaluate the effectiveness of specific nursing
      interventions with the patient population with peripheral vascular disease. This
      knowledge will strengthen the scientific basis for nursing practice. For the
      purpose of facilitating increased participation in nursing research by members of
      the Society for Vascular Nursing, the authors presented the following article, "
      RESEARCH: Conception to Completion," at the Tenth Annual Symposium in Chicago.
      The author's current research entitled, "The Effects of Nurse Follow-Up on
      Increasing Self Care in Patients With Peripheral Vascular Disease: A Prospective
      Randomized Study," is used as a prototype to illustrate the conceptual, empiric,
      and interpretive phases of the research process. As the Society for Vascular
      Nursing moves into its second decade, members will become more focused on
      research that will generate new knowledge and validate current practices as
      vascular specialists. There is a great need for the generation and dissemination
      of knowledge that will help nurses better understand adaptation to health and
      illness. From this knowledge must come clinical strategies that assist people to
      promote their own health or cope with illness and its effects on their lives.
      Vascular specialists must be at the forefront of this effort. Furthermore, the
      era of cost containment has resulted in increasing pressure to document what
      nurses do and the differences they make in the outcomes of patient care. The most
      important outcome of clinical nursing research is the potential benefit it offers
      to patients. This article will review the steps in conducting nursing research.

PMID- 8286282
TI  - Practicing nursing research: Part 3. Critiquing the hard part: research design
      and data analysis.

PMID- 8286283
TI  - Magnetic resonance angiography: imaging the distal circulation.

PMID- 8286284
TI  - Urokinase therapy in mesenteric venous thrombosis: a case study.
AB  - Mesenteric venous thrombosis is an emergency usually treated by bowel resection
      with an end-to-end anastomosis and in some cases anticoagulant therapy. The
      survival rate is low. The literature records many cases of mesenteric venous
      thrombosis and various treatment modalities. An 18-year-old man was successfully
      treated for mesenteric venous thrombosis by the placement of a femoral infusion
      catheter in the superior mesenteric artery for continuous infusion of urokinase
      (Abbot Laboratories, N. Chicago, Ill.). This case study and overview of the
      disease process reviews the nursing implications of this problem.

PMID- 8286285
TI  - Continuing medical education.

PMID- 8286286
TI  - Surgical accuracy in orthognathic surgery.
AB  - This study investigated the accuracy with which the planned surgical change could
      be achieved during orthognathic surgery, based upon the retrospective
      cephalometric analysis of 62 patients who received correction of dentofacial
      deformity. It is concluded that, despite individual variation, no statistically
      significant difference could be demonstrated between the orthognathic prediction
      and the surgical outcome. This supports both the use of orthognathic profile
      planning and the surgeon's ability to follow the plan.

PMID- 8286287
TI  - Preoperative intravenous diclofenac for postoperative pain prevention in
      outpatients.
AB  - Fifty patients undergoing a standard removal of an impacted lower third molar
      were given a single dose of 75 mg sodium diclofenac or saline (placebo)
      intravenously before operation, on a double-blind basis. Pain was measured
      postoperatively by means of a visual analogue scale hourly for the first 8 h and
      during the first and second days after operation. Administration of diclofenac
      resulted in greater pain relief than administration of placebo for the first 3 h
      after surgery, whereafter the treatments did not differ. The results suggest that
      intravenous preoperative diclofenac may be useful in some clinical situations but
      generally it probably offers little benefit over the corresponding oral
      treatment.

PMID- 8286288
TI  - Knowledge of wisdom tooth removal: influence of an information leaflet and
      validation of a questionnaire.
AB  - Different methods are now being employed to increase patient's knowledge of
      operative procedures for the purpose of ensuring informed consent and improving
      satisfaction with the service provided. Information leaflets are being used as an
      additional aid in general practice and in hospital units but many are ambiguous
      and poorly designed. The evaluation of such written information is seldom
      conducted. Where evaluation has been reported, the measures employed to assess
      the benefit of the intervention are poorly validated. This study was conducted to
      help validate a measure of knowledge concerning removal of impacted third molar
      and to assess in the longer term the effect of the introducing an information
      leaflet for patients attending the oral surgery clinic at a dental teaching
      hospital. Predictions were made about how the knowledge scale would perform under
      certain conditions. These predictions were subsequently tested in a sample of 156
      subjects: dental students (n = 55), sixth-formers (n = 50) and relatives of
      patients attending a dental hospital (n = 51). All the predictions made about the
      behaviour of the new scale were confirmed, thereby strengthening the validity of
      the newly designed measure. This approach of conducting preliminary work to gain
      an understanding of a new measure's behaviour is advocated as an essential first
      step in the evaluation of initiatives to provide patient information about dental
      and oral surgical procedures.

PMID- 8286289
TI  - The use of third molar surgery in clinical pharmacology.
AB  - This review discusses the various sequelae that arise after third molar surgery
      and their use for assessing the efficacy of a variety of therapeutic measures.
      The surgical procedure provides an opportunity to investigate onset, depth,
      duration and possible systemic effects of local anaesthetic solutions. Also, the
      anxiety which often accompanies such surgery lends itself to the appraisal of
      different anxiolytic agents and sedation techniques. The immediate postoperative
      sequelae of pain, buccal swelling and trismus provides a useful clinical model
      for evaluating the efficacy of analgesics and anti-inflammatory drugs. Third
      molar tooth sockets are susceptible to infection and this propensity enables the
      assessment of different antibiotic regimens. A further advantage of the third
      molar model is its application for crossover studies, with the patient acting as
      their own control. Very few surgical procedures afford this facility, which
      further adds to the value of this model in clinical pharmacology.

PMID- 8286290
TI  - A comparative animal experimental study of differently dimensioned osteosynthesis
      screws used in the mid-face.
AB  - The soft tissue covering most of the midfacial skeleton is relatively thin. On
      account of this plates and screws of the 2 mm systems used in the osteosynthesis
      of this region can bulge and/or be palpable through the thin integument. This
      shortcoming has prompted the need to develop smaller systems. The present study
      was designed to investigate whether these more delicate systems are capable of
      withstanding the midfacial forces that come to bear during functional
      mastication. For the study a Le Fort I osteotomy was carried out in 10 sheep. The
      mobile maxilla was fixed with osteosynthesis plates and screws. This paper
      reports on 40 plates and 170 screws of two AO titanium systems. It compares the
      strength of 1.5 mm and 2.0 mm AO screws. The anchorage of the screws was assessed
      by evaluating the nature of contact between the screw and interfacial bone. The
      loaded screws showed no discernible differences in postoperative bone remodelling
      that could be correlated to the osteosynthesis systems. Although the experimental
      situation may not be directly comparable to the trauma or osteotomy case, this
      study lends credibility to the assumption that the 1.5 mm screw system could be
      used instead of the 2.0 mm system, even in mid-face areas associated with high
      masticatory loads.

PMID- 8286291
TI  - Location of the mandibular canal within the atrophic mandible.
AB  - In 43 edentulous, lower jaw halves, sections were carried out in the area between
      the mental foramen and the third molar. The relative changes in the location and
      course of the mandibular canal which are caused by atrophy were analysed. For
      this purpose, the mandibles were classified according to so-called residual ridge
      orders which describe the different stages of alveolar ridge resorption. The
      following findings were obtained: The distance between the mandibular canal and
      the lingual and buccal external border does not change in any stage of the
      atrophic process, i.e. it remains conspicuously constant. However, the distance
      between the mandibular canal and the cranial and caudal borders of the body of
      the mandible partly changes to a statistically highly-significant extent, the
      distance between the canal and the atrophic alveolar ridge being affected more
      strongly than that between the canal and the base of the mandible. These changes
      were most clearly pronounced in the area of the first molar.

PMID- 8286292
TI  - The compressible silicone rubber prosthesis in temporomandibular joint disease.
AB  - An alternative technique for temporomandibular joint arthroplasty is described,
      in which the mandibular condyle is replaced by a soft compressible silicone
      rubber prosthesis. A modified Nicolle-Calnan metacarpo-phalangeal joint
      prosthesis was used to reconstruct 31 joints in 24 patients. Results suggest that
      in those patients where there has been no loss of the prosthesis, function
      continues to be markedly improved when compared with the pre-operative condition.
      Painful symptoms were relieved in cases of specific joint pathology but the
      technique was of little value in the management of dysfunctional pain when
      radiographic evidence of joint pathology was absent. A specifically designed TMJ
      prosthesis of this type may be a useful addition to the surgeon's armamentarium.

PMID- 8286293
TI  - Split-thickness skin grafted stent for upper airway patency after medial
      maxillectomy.

PMID- 8286294
TI  - Infiltrating lipoma of the mental region: report of a case.
AB  - Lipoma is an uncommon tumour in the oral cavity. Infiltrating lipoma is extremely
      rare. An infiltrating lipoma of the mental region in a 48-year old woman is
      reported. Wide myectomy was performed, and follow-up showed excellent healing
      without recurrence.

PMID- 8286295
TI  - Systemic immunosuppression and oral malignancy: a report of a case and review of
      the literature.
AB  - A case is described of squamous cell carcinoma (SCC) of the lower lip in a
      patient receiving systemic immunosuppression. Contemporary theories on the
      aetiology of malignancy in such systemically immuno-compromised patients are
      discussed.

PMID- 8286296
TI  - Dysplastic pleomorphic adenoma of the sublingual salivary gland.
AB  - All tumours of the sublingual gland are rare and paradoxically the large majority
      are malignant. A case of pleomorphic adenoma in the sublingual gland is
      described. The tumour showed areas of dysplasia and the difficulties in
      distinguishing this from benign pleomorphic adenoma or carcinoma in pleomorphic
      adenoma are considered, and the literature is reviewed.

PMID- 8286297
TI  - Citation for presentation of the 1992 Down Surgical Prize to Russell Hopkins OBE,
      FDSRCS, MRCS, LRCP.

PMID- 8286298
TI  - The aetiology of Class III malocclusion examined by tensor analysis.
AB  - This study compares and contrasts the differences in facial pattern between
      groups of young people, employing a modified tensor analysis. One-hundred-and
      thirty-eight children with Class III malocclusions were compared with 105 control
      individuals of similar ages: 126 subjects were prepubertal (age range 7 to 10
      years), whilst the remaining 117 were between 15 and 22 years of age. Males and
      females were examined separately. The tensor analysis permitted the computation
      of differences in form (that is in size and shape) without specifically measuring
      either. Mean values for 18 conventional cephalometric landmarks were determined
      for each sub-group of control and Class III individuals. Customized programs were
      developed to assess the differences between 23 triads of points between the two
      occlusal groups.

PMID- 8286299
TI  - Surface roughness and droplet contact angle measurement of various orthodontic
      bonding cements.
AB  - Surface characteristics that are considered important for bacterial attachment to
      thirteen orthodontic bonding composite cements and one glass ionomer cement were
      examined in vitro before and after toothbrush abrasion. The surface roughness and
      contact angle measurements were found to be statistically significantly different
      between the materials, both before and after brushing, and there were also
      statistically significant changes within materials after brushing. There were low
      correlation coefficients between surface roughness and contact angle for both pre
      and post-brushed materials.

PMID- 8286300
TI  - The clinical evaluation of a fluoride-containing orthodontic bonding material.
AB  - A clinical trial comparing a conventional adhesive, Concise, with a new fluoride
      containing composite cement is described. The bond failure rate, plaque score,
      gingival health, and enamel decalcification were assessed for each material after
      a minimum period of 1 year. The preliminary results show no significant
      difference between the two materials for each of the variables examined, although
      there was a reduction in the number of white spot lesions using the fluoride
      containing composite. The level of fluoride ion concentration required to inhibit
      the growth of oral micro-organisms is discussed.

PMID- 8286301
TI  - The development of a new method of cephalometric and study cast mensuration with
      a computer controlled, video image capture system. Part II: Study cast
      mensuration.
AB  - A computerized system for mensuration of dental casts, developed at the Royal
      Berkshire Hospital in Reading was tested against a conventional manual method and
      a computer controlled reflex microscope. Systematic errors, calibration, and
      handling aspects are discussed. Results showed that the computerized system
      provided data which while statistically different, were clinically comparable
      with the same measurements carried out using conventional manual or digitizing
      techniques. The results indicated that future research is required with respect
      to object illumination for all indirect techniques.

PMID- 8286302
TI  - The relationship of crowding to the eruptive position of the lower permanent
      incisors.
AB  - The aim of this study was to examine the positions of newly erupted lower
      permanent incisors and their relationship to crowding. Forty-one crowded and 37
      uncrowded dental casts of children in the early mixed dentition were examined by
      means of digitization using a reflex microscope. Two aspects of alignment were
      considered: rotation and labio-lingual displacement. Rotations of the incisors
      were defined as deviations from 'ideal' predicted angles. Displacement of the
      incisors was measured as the distance between the most labial and most lingually
      placed incisors. The study showed an increase in rotations amongst the crowded
      sample. The result of the investigation of the relationship between crowding and
      displacement was inconclusive. There would appear to be significant differences
      between the positions of newly erupted crowded and uncrowded incisors. Crowding,
      however, was not the only factor causing irregularity.

PMID- 8286303
TI  - The incidence and prevention of ocular injuries in orthodontic practice.
AB  - A postal survey was conducted to determine the use of eye protection and
      incidence of ocular trauma in orthodontic practice. One-hundred-and-fifty-nine
      NHS orthodontic consultants and 203 specialist orthodontic practitioners were
      surveyed. Two-hundred-and-forty-one (66.5 per cent) replies were received. Some
      form of eye protection was routinely worn by 66.8 per cent of orthodontists, 64.3
      per cent of patients, but only 33.6 per cent of DSAs. Eye protection was not
      offered to DSAs in 31.9 per cent of practices or to patients in 22.1 per cent.
      Forty-three per cent of orthodontists reported instances of ocular injury in
      their practices. The majority of these injuries (n = 104) occurred during
      debonding or trimming acrylic. Other incidents involved ligating materials, intra
      oral polishing, and acid etching. Most injuries (83.5 per cent) were treated in
      the surgery without any long-term effects. The routine use of goggles or
      spectacles with side-pieces and plastic lenses, which conform to British Standard
      BS 2092, is recommended for staff and patients during all operative procedures in
      orthodontic practice.

PMID- 8286304
TI  - The provision of orthodontic care in the general dental services of England and
      Wales: extraction patterns, treatment duration, appliance types and standards.
AB  - A systematic sample of 1010 cases was collected by the Dental Practice Board. The
      commonest type of treatment involved extraction of the first premolars followed
      by removable appliances. Treatment duration was on average 1.9 years, one-arch
      fixed appliances were started in an older age group and two-arch fixed appliance
      treatment took longer to complete than other appliance types. The best standard
      of treatment was achieved using upper and lower fixed appliances.

PMID- 8286305
TI  - Use of the PAR index in assessing the effectiveness of removable orthodontic
      appliances.
AB  - The dental study casts of 150 consecutively completed removable appliance cases
      were examined before and after orthodontic treatment using the PAR index. Eighty
      nine per cent were classified either as 'improved' or 'greatly improved'. Of the
      16 cases classified as 'worse, no different', six were mixed dentition cases with
      limited treatment objectives (which were successfully achieved) and three were
      permanent dentition cases where only one tooth was being aligned. Using
      predefined criteria removable appliances were shown to be most effective in
      treating cross-bites, ectopic tooth position, anterior spacing, and overjet, and
      less effective in treating crowding, rotations, and molar relationships.

PMID- 8286306
TI  - Guidance on presentation of cephalometry-based research studies. A personal
      perspective.
AB  - This paper presents advice on the planning and presentation of cephalometric
      investigations.

PMID- 8286307
TI  - Hard times.

PMID- 8286308
TI  - Gloves: a recommended aid in cross infection control in orthodontics. A
      comparison of gloves available from UK supply houses.

PMID- 8286309
TI  - Infection crossed--a very personal viewpoint.

PMID- 8286310
TI  - Late forming supernumeraries in the mandibular premolar region.

PMID- 8286311
TI  - Orthodontic audit.

PMID- 8286312
TI  - [The resistance to drainage of the aqueous humor].
AB  - The presence of the evacuation paths of aqueous humor at the level of the
      camerular angle makes it play an important role on open angle glaucoma pathology.
      The fundamental element in the evacuation of aqueous humor is the endothelial
      cell, who has a main contribution to the routing of aqueous humor using the
      phenomenon called micropinocytosis. With the age the number of endothelial cells
      diminishes, their function reduces and an atypical collagen appears, together
      with the thickness of the basal membrane, the agglutination of the trabecular
      blades and Schlemm channel collapse. The fact is that the raise of the evacuation
      resistance in open angle glaucoma must not be interpreted mechanically; a
      research from a biochemical and molecular point of view must be completed.

PMID- 8286313
TI  - [The effect of meteorological factors on the body in general and on the eye in
      particular].
AB  - Some data of the literature concerning the action of the weather factors on the
      human body are presented. In the same time the knowledge about the modifications
      induced in the healthy organism by the atmospheric factors and the biotropical
      action of the weather factors and about some ocular diseases, whose evolutions in
      made worse by the weather factors, is summarized.

PMID- 8286314
TI  - [The ocular manifestations of AIDS in children].
AB  - The exam of 33 children with AIDS revealed in 10 cases manifestations of the
      anterior pole and of ocular anexes specific to this infection. In 8 cases we
      noticed seborrheic dermatitis, exudative dermatitis. Molluscum contagiosum,
      staphilococies, papoulous eruptions . In 3 cases there were herpetic infections,
      one of them was corneal localized. In one case was Burkitt lymphoma with
      palpebral exteriorization. The fundus exam revealed retinal microvasculopathies
      with aneurysmal dilatations in cases and retinal hemorrhages in 3 cases. The
      discrete found in 8 cases, in 2 cases was bilateral papillary and papilloretinal
      edema was papillary stasis. In 8 cases was partial optical atrophia and in one
      case we noticed tapetoretinal degenerescente. The aid of the ophthalmologist in
      the thorough examination of children having AIDS was important, in spite of the
      unspecific nature of the noticed lesions.

PMID- 8286315
TI  - [Sympathetic ophthalmia in a case of neurilemmoma of the ciliary body].
AB  - The paper presents the case of a 62-year-old male patient, which has been
      hospitalized with the symptomatology of a acute glaucoma through intumescent
      lens. After the lens extraction, the globe evolution was to atrophy with chronic
      irrigation, starting a hypertensive cyclitis at the other eye, assumed to be a
      sympathetic ophthalmia. After several acute evolutive episodes at both eyes, the
      enucleation of the primal eye was made and a ciliary body tumour (neurinoma) was
      discovered. After enucleation under general and local cortisone treatment, the
      inflammatory phenomena at the sympathetic eye were entering in remission; but the
      hypertony, which was considered to be an open-angle pre-existent glaucoma, was
      persistent. The paper also discusses the sympathetic ophthalmia producing
      mechanism the characteristics of the ciliary body tumour and the diagnosis
      problems raised by this case.

PMID- 8286316
TI  - [Simultaneous bilateral occlusion of the central retinal artery].
AB  - There are presented two rare cases of bilateral and simultaneous OACR. In the
      last year's literature there were founded a few cases of bilateral and
      simultaneous OACR described as occurring during other diseases. After the clinic
      and laboratory investigation, the authors consider the two cases'
      etiopathogenesis being part: first of a ischemic anterior arterial neuropathy and
      the second case part of a nonarterial neuropathy. Further, there are commented
      the manifestations and the immediate therapy of the ischemic optic neuropathy.
      Finally, the authors propose the immediate use of corticosteroids in high doses
      simultaneous with the classic treatment: vasodilators , anticoagulant drugs,
      thrombolytic agents. The purposes are to save the affected eye and especially to
      prevent the appearance of the disease to the second one.

PMID- 8286317
TI  - [Progressive nuclear external ophthalmoplegia].
AB  - 66-year-old female patient presents palpebral bilateral ptosis and external
      ophthalmoplegia with a progressive evolution. The clinical aspects are completed
      with the affectation of the sensitive and motor trigemen, with the masseter
      atrophy and bilateral trophic keratitis. The affectation of the facial and
      acoustic nerves was associated with bilateral perception surditate. The
      hereditary transmission was dominant, with incomplete penetration. The neurogenic
      pathogeny was sustained on the basis of the association of neurological
      multilesions with III, IV, V, VI, VII, VIII nerves, with progressive extension.

PMID- 8286318
TI  - [The macular vascular changes in diabetic retinopathy].
AB  - The angiofluorographic surveys done on 46 patients with diabetes shows some
      particular modifications of the retinal vessels, from the foveolar, perifoveolar
      and parafoveolar areas. These modifications influence the values of the visual
      acuity; they are not connected in all cases with all the retinal vascular
      modifications.

PMID- 8286319
TI  - [Secondary glaucoma in the Weill-Marchesani syndrome].
AB  - The observation on a female patient with anterior underluxation of the lens at
      the right eye, secondary absolute glaucoma at the right eye, posterior luxation
      of the lens at the left eye, pathological cataract at both eyes. The general
      somatic exam shows low tallness, short members, brachydactyly and reduced
      functional mobility. The clinical manifestations point out a Weill-Marchesani
      syndrome . The underluxation of the lens determined secondary glaucoma in the
      absolute stage at the right eye, while the evolution of the lens luxation in
      vitreous at the left eye kept the visual function. The secondary glaucoma in the
      Weill-Marchesani syndrome is not a compulsory complication of it.

PMID- 8286320
TI  - [Autosomal dominant transmission in retinitis pigmentosa].
AB  - The family tree, including 5 generations, of a female patient with typical
      retinitis pigmentosa has been studied. The transmission was irregular autosomal
      dominant the gene being manifest for 5 generations both to men and women. The
      gene penetration was 64%; less than evolution of the illness to bilateral cecity.
      The case seem to be closely related with the recessive forms of transmission.

PMID- 8286321
TI  - [Ophthalmic migraine].
AB  - Ophthalmic migraine is a particular form of essential vascular headache, which is
      determined by modification of the vascular tonus at the level of intracranial
      vessels, especially at the level of occipital cortex. The paper presents the case
      of a 41-year-old male patient with typical symptoms of ophthalmic migraine which
      started two years ago. The ocular examination of both eyes is normal. The
      clinical and paraclinical investigation did not reveal any biological and
      neuroendocrine dysfunction.

PMID- 8286322
TI  - [Sectorial retinitis pigmentosa and acoustic neurinoma].
AB  - The case of a 56-year-old female patient is presented; she was hospitalized for
      decreased vision of both eyes, discrete hemeralopia, vertigo, right hypoacusis
      and occipital headache. The eye fundus examination showed lesions of retinitis
      pigmentosa in the inferotemporal sector and decreased arterial calibre. The
      patient was diagnosed neurologically as a right acoustic neurinoma with
      pontocerebellar syndrome. No other cases with the same symptomatology were
      noticed in the patient's family.

PMID- 8286324
TI  - [New concepts in the approach to congenital strabismus].
AB  - The first part of the paper reviews the clinical symptoms of congenital
      strabismus. Congenital strabismus passes four stages during its evolution.
      Spontaneous evolution becomes either alternant strabismus (stage IV a) or
      monolateral strabismus (stage IV b). The early treatment is to direct the
      evolution to the "a" form of stages III and IV and mainly consists of optical
      correction and occlusion.

PMID- 8286323
TI  - [Albuminuric neuroretinopathy in chronic primary glomerulonephritis].
AB  - The case of a 23-year-old young patient, which had an impure nephrotic syndrome
      and chronic glomerulonephritis, is presented. The evolution was to arterial
      hypertension, azotemia and albuminuria. The symptomatology was dominated by the
      ocular signs of AHT and albuminuric neuroretinopathy. The physiopathological
      mechanisms were of immunological type, starting an inflammatory chronic process
      at the level of renal glomeruli, together with the diminishing of the glomerular
      filtration and the appearance of a hypertension in the arterial sector, including
      the ocular area. The exact diagnosis was the result of a good cooperation between
      the physician and the ophthalmologist.

PMID- 8286325
TI  - [Clinical ocular electrophysiology].
AB  - The paper summarizes the aspects connected with the clinical interpretation of a
      normal or modified electric path, together with the indications of the
      electrophysiological exploration use and the contributions to the diagnosis and
      prognosis in ocular diseases. The methods are complementary ore to each other and
      must be interpreted together with the clinical, ophthalmological, adaptometrical
      and neuro-ophthalmological data.

PMID- 8286326
TI  - NMR evidence for similarities between the DNA-binding regions of Drosophila
      melanogaster heat shock factor and the helix-turn-helix and HNF-3/forkhead
      families of transcription factors.
AB  - Heteronuclear multidimensional NMR experiments of residues 33-163 of the DNA
      binding domain of Drosophila heat shock factor, dHSF(33-163), were recorded,
      using only 3 mg of uniformly 15N-labeled or 2 mg of uniformly 15N/13C-labeled
      protein. The polypeptide consists of a structured part comprising three helices,
      a three-stranded antiparallel beta-sheet, with the first two strands connected by
      a four-residue type I tight turn. The second helix is disrupted at its C-terminal
      end by a proline residue and is followed by an extended turn, leading to the
      third helix. The dHSF(33-163) protein is unstructured at its N- and C-termini,
      and a third unstructured region is found from Thr113 to Arg124. Exchange
      broadening of the 15N-1H correlations upon titration of 15N labeled HSF with a 13
      base-pair DNA duplex suggests a DNA-binding motif in which the third helix acts
      as the recognition helix. Both the secondary structure and DNA-binding pattern of
      dHSF(33-163) suggest that the overall topology resembles that the helix-turn
      helix bacterial activator CAP [Weber, I. T., & Steitz, T. A. (1987) J. Mol. Biol.
      198, 311-326] and the liver-specific transcription factor HNF-3 gamma, the
      prototype of the HNF-3/forkhead protein family [Clark, K. L., Halay, E. D., Lai,
      E., & Burley, S. K. (1993) Nature 364, 412-420].

PMID- 8286327
TI  - Equilibrium unfolding studies of barstar: evidence for an alternative
      conformation which resembles a molten globule.
AB  - The folding of the small protein barstar, which is the intracellular inhibitor to
      barnase in Bacillus amyloliquefaciens, has been studied by equilibrium unfolding
      methods. Barstar is shown to exist in two conformations: the A form, which exists
      at pH values lower than 4, and the N state, which exists at pH values above 5.
      The transition between the A form and the N state is completely reversible. UV
      absorbance spectroscopy, fluorescence spectroscopy, and circular dichroism
      spectroscopy were used to study the two conformations. The mean residue
      ellipticity measured at 220 nm of the A form is 60% that of the N state, and the
      A form has some of the properties expected for a molten globule conformation.
      Fluorescence energy transfer experiments using 1-anilino-8-naphthalenesulfonate
      indicate that at least one of the three tryptophan residues in the A form is
      accessible to water. Surprisingly, high concentrations of denaturant are required
      to unfold the A form. For denaturation by guanidine hydrochloride, the midpoint
      of the cooperative unfolding transition measured by circular dichroism for the A
      form at pH 3 is 3.7 +/- 0.1 M, which is significantly higher than the value of
      2.0 +/- 0.1 M observed for the N state at pH 7. The unfolding of the A form by
      guanidine hydrochloride or urea is complex and cannot be satisfactorily fit to a
      two-state (A<==>U) model for unfolding. Fluorescence-monitored tertiary structure
      melts before circular dichroism-monitored secondary structure, and an equilibrium
      unfolding intermediate must be present on the unfolding pathway of A.

PMID- 8286328
TI  - Characterization of covalently bound enzyme inhibitors as transition-state
      analogs by protein stability measurements: phosphonate monoester inhibitors of a
      beta-lactamase.
AB  - An experimental method is described for determining whether a covalent enzyme
      inhibitor complex has the properties expected of a transition-state analog. The
      method involves a comparison of the noncovalent interaction energies between the
      enzyme and the inhibitor on one hand (determined from protein denaturation
      thermodynamics) and the analogous transition state on the other (determined from
      kinetic measurements). These two quantities should presumably be large (in
      comparison with the interaction energies of substrates or reaction intermediates)
      and close to equal for a good transition state analog; the former is seen
      dramatically in a large increase in protein stability. The method is absolute in
      the sense that it does not require a crystal structure of the inhibited enzyme or
      any preconceptions as to the mechanism of action of the enzyme except those which
      led to adoption of the potential transition state analog and which might turn out
      to be right or wrong. In this paper the method is quantitatively applied to the
      inhibition of the Staphylococcus aureus PC1 beta-lactamase by phosphonate
      monoesters. It is concluded that the enzyme-inhibitor complex in this case is
      likely to be a good transition-state mimic. Therefore, mechanistic interpretation
      of the crystal structure of the complex can be made with more confidence. A
      semiquantitative assessment of the situation with serine proteinases is also
      made. It is concluded, in agreement with predictions based on the generally
      accepted mechanism and on crystal structures, that anionic, but not neutral,
      phosph(or/on)yl derivatives are good transition-state analogs.

PMID- 8286329
TI  - Inhibition and inactivation of the F1 adenosinetriphosphatase from Bacillus PS3
      by dequalinium and activation of the enzyme by lauryl dimethylamine oxide.
AB  - The F1-ATPase from Bacillus PS3 (TF1) hydrolyzes 50 microM ATP in three kinetic
      phases. An initial burst rapidly decelerates to a partially inhibited,
      intermediate phase, which, in turn, gradually accelerates to an uninhibited,
      final steady-state rate. Lauryl dimethylamine oxide (LDAO) stimulates the final
      rate over 4-fold. The stimulatory effect saturates at about 0.1% LDAO. Under
      these conditions, the intermediate phase is nearly absent. Dequalinium inhibits
      TF1 reversibly in the dark in the presence or absence of LDAO. The apparent
      affinity of TF1 for dequalinium increases in the presence of LDAO. Dixon plots of
      the initial rates of the intermediate phase and the final rates against
      dequalinium concentration at a series of fixed ATP concentrations in the presence
      and absence of 0.03% LDAO indicate noncompetitive inhibition in each case.
      Replots of the slopes of the Dixon plots for the initial rate of the intermediate
      phase and the final rate against 1/[ATP] reveal apparent Km values of 770 microM
      and 144 microM, respectively, when obtained in the absence of LDAO. The apparent
      Km values determined from the data obtained in the presence of LDAO for the same
      phases are 303 microM and 163 microM, respectively. These results suggest that
      LDAO stimulates ATPase activity either by increasing the affinity of noncatalytic
      sites for ATP, which promotes release of inhibitory MgADP from a catalytic site,
      or by directly promoting release of MgADP from the affected catalytic site.
      Dequalinium retards this process without affecting the affinity of noncatalytic
      sites for ATP. When irradiated in the presence of dequalinium, TF1 is rapidly
      inactivated with an apparent Kd of 12.5 microM in the presence or absence of
      LDAO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286330
TI  - Equilibrium folding studies of cellular retinoic acid binding protein, a
      predominantly beta-sheet protein.
AB  - We have examined the conformational behavior under various unfolding conditions
      of a predominantly beta-sheet protein, cellular retinoic acid binding protein
      (CRABP). Urea unfolding-refolding of CRABP is a highly cooperative process that
      can be approximated by a two-state model. Acid denaturation is also cooperative
      and reversible and leads to a state containing nonnative residual structure:
      Below pH 2.6, CRABP contains a substantially larger amount of alpha-helix than
      under native conditions. CRABP adopts up to 75% alpha-helix in solutions
      containing a high percentage of 2,2,2-trifluoroethanol. The acid-denatured state
      of CRABP undergoes a conformational change to a state containing predominantly
      beta-sheet structure upon the addition of small amounts of Na2SO4. This
      conformational malleability may be important for the folding mechanism of CRABP.
      The possible implication of nonnative alpha-helical structure in the folding of
      CRABP is discussed.

PMID- 8286331
TI  - Isoform differences in substrate recognition by glycogen synthase kinases 3 alpha
      and 3 beta in the phosphorylation of phosphatase inhibitor 2.
AB  - Phosphorylation of inhibitor 2, the regulatory subunit of the ATP-Mg-dependent
      protein phosphatase, by glycogen synthase kinase 3 (GSK-3) causes activation of
      the phosphatase. Prior phosphorylation by casein kinase II has been shown to
      enhance both phosphorylation and activation of the phosphatase by GSK-3 (DePaoli
      Roach, A. A. (1984) J. Biol. Chem. 259, 12144-12152). Reported here is a
      comparison of the phosphorylation of inhibitor 2 by two defined isoforms of GSK
      3, GSK-3 alpha and GSK-3 beta. GSK-3 beta was a significantly better inhibitor 2
      kinase than was GSK-3 alpha. The Vmax/Km value for GSK-3 beta was approximately
      10-fold higher than that for GSK-3 alpha. GSK-3 beta phosphorylated inhibitor 2
      to a stoichiometry of approximately 1.0 mol of phosphate/mol of inhibitor 2. The
      phosphorylation by GSK-3 beta was determined to be exclusively at Thr-72 on the
      basis of the inability of the enzyme to modify a mutant inhibitor 2 in which Thr
      72 was changed to alanine. Prior phosphorylation by casein kinase II promoted the
      action of GSK-3 alpha in keeping with earlier reports using undefined GSK-3
      preparations. Phosphorylation by GSK-3 beta, in contrast, was unaffected by the
      previous action of casein kinase II. These results suggest that there can be
      important differences in substrate recognition by different isoforms of the same
      protein kinase and may help explain why some reported GSK-3 substrates require
      prior phosphorylation whereas other do not.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286332
TI  - In vivo phosphorylation site of hexokinase 2 in Saccharomyces cerevisiae.
AB  - Yeast hexokinase 2 is known to be a phosphoprotein in vivo, prominently labeled
      from 32P-inorganic phosphate after a shift of cells to medium with low glucose
      concentration [Vojtek, A. B., & Fraenkel D. G. (1990) Eur. J. Biochem, 190, 371
      375]. The principal and perhaps sole site of phosphorylation is now identified as
      residue serine-15, by observation of a single tryptic peptide difference, its
      sequencing and size determination by mass spectrometry, and by mutation to
      alanine, which prevents phosphorylation in vivo. Although protein kinase A was
      unlikely to accomplish the phosphorylation in vivo, serine-15 does belong to a
      protein kinase A consensus phosphorylation sequence, and in vitro phosphorylation
      by protein kinase A at serine-15 could be shown by labeling and by peptide
      determination. The alanine-15 mutant enzyme was not phosphorylated in vitro.

PMID- 8286333
TI  - Resonance Raman spectra of the intermediates in phototransformation of large
      phytochrome: deprotonation of the chromophore in the bleached intermediate.
AB  - Resonance Raman (RR) scattering from type A large phytochrome of pea was measured
      at cryogenic as well as ambient temperatures to determine an intermediate in
      which deprotonation of the chromophore takes place. The RR bands of the red
      absorbing (Pr) and far-red-absorbing forms (Pfr) of large pea phytochromes at
      ambient temperatures are almost the same in their frequencies as those of the
      intact form reported previously (Mizutani et al., 1991). The RR spectrum of large
      phytochrome excited at 364 nm at -120 degrees C, where Pr and a
      photointermediate, I700 (= lumi-R), are trapped, showed a strong band at 1625 cm
      1 with a shoulder at 1648 cm-1 in the C C=C stretching region. The shoulder
      disappeared, and a new band appeared at 1597 cm-1 upon raising the temperature to
      -80 degrees C, where transformation from I700 to meta-Ra proceeds. The RR spectra
      remained unchanged until -10 degrees C, indicating that the RR spectra of meta-Rb
      and meta-Rc are close to that of meta-Ra, and we call them comprehensively the
      bleached intermediate, Ibl. At ambient temperatures where photo-steady-states
      among a few species are attained, strong RR bands were observed at 1625 and 1599
      cm-1 upon excitation at 364 nm under simultaneous far-red illumination, and the
      1599-cm-1 band was appreciably intensified under simultaneous red- instead of far
      red illumination. By comparison of these spectra with those at low temperatures,
      the 1625- and 1599-cm-1 bands were reasonably assigned to Pr and Ibl,
      respectively. A chemically prepared model of the bleached form, Pbl, also gave a
      prominent band at 1599 cm-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286334
TI  - Studies on the assembly of complex II in yeast mitochondria using chimeric
      human/yeast genes for the iron-sulfur protein subunit.
AB  - A series of chimeric human/yeast IP genes were constructed in order to
      investigate domains of the iron-sulfur protein (IP) that are important for
      assembly and/or activity of complex II of the electron transport system in
      Saccharomyces cerevisiae. These genes were expressed in a respiration-deficient
      yeast mutant in which the endogenous IP gene had been disrupted. Substitutions at
      the N-terminus were tolerable. Substituting the region covering the first iron
      sulfur center [2Fe-2S] had no effect on assembly, while activity decreased 2-5
      fold. The addition of seven amino acids from the human peptide, including four
      charged residues, at the C-terminus did not perturb either assembly or activity.
      A region between the first and second cysteine clusters was identified which when
      substituted caused a complete failure in the assembly of complex II. It includes
      a 15 amino acid stretch which shows the greatest variability between species.
      Larger substitutions including this segment failed as well. Exchanging the region
      between the second and third cysteine clusters making up the [4Fe-4S] and [3Fe
      4S] centers enabled transformants to grow on nonfermentable carbon sources, yet
      no SDH activity was observed in vitro. The IP and FP proteins accumulate to wild
      type levels in these mutants. We speculate that the lack of observed activity is
      due to the lability of iron-sulfur centers in isolated, broken mitochondria.

PMID- 8286335
TI  - Thiophene derivatives as new mechanism-based inhibitors of cytochromes P-450:
      inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic
      acid.
AB  - Oxidation of tienilic acid (TA) by microsomes of yeast expressing two closely
      related human liver cytochrome P-450s (P450), P450 2C9 and 2C10, led to catalysis
      dependent loss of activity of these P450s. Under identical conditions, oxidation
      of a tienilic acid isomer (TAI) failed to give any P450 inactivation. The loss of
      P450 activity during TA oxidation was concomitant with product (5-hydroxytienilic
      acid, 5-OHTA) formation, showed pseudo-first-order and saturation kinetics, and
      was inhibited by an alternative substrate, tolbutamide. Covalent binding of TA
      metabolites to microsomal proteins occurred in parallel with enzyme inactivation
      and was partially inhibited by the presence of glutathione in the reaction
      medium. However, glutathione did not protect P450 enzyme from inactivation. Thus,
      TA exhibited all of the characteristics of a mechanism-based inactivator for P450
      2C9 and 2C10 enzymes. The following kinetic parameters were determined in the
      case of P450 2C10: t1/2,max = 3.4 min, k(inact) = 3.6 10(-3) s-1, KI = 4.3
      microM, k(inact)/KI = 813 L mol-1 s-1, and partition ratio = 11.6. Moreover, a
      specific covalent binding of 0.9 mol of TA metabolite per mole of P450 2C10 was
      found to occur before the complete loss of enzyme activity (in incubations
      performed in the presence of glutathione). A plausible mechanism for P450 2C10
      (2C9) inactivation during TA oxidation is proposed. It involves the intermediate
      formation of an electrophilic thiophene sulfoxide, which may react at position 5
      of its thiophene ring either with H2O to give 5-OHTA or with a nucleophilic group
      of an amino acid residue of the P450 active site, which results in its covalent
      binding to P450 protein. This alkylation and inactivation of P450 2C9 (2C10) by
      TA could be a starting point for the appearance of anti-P450 2C antibodies
      detected in patients treated with TA and suffering from immunoallergic hepatitis.

PMID- 8286337
TI  - Application of exciton coupling theory to the structure of mitochondrial
      cytochrome b.
AB  - The circular dichroism of the reduced bis-heme mitochondrial cytochrome b in the
      Soret region has been analyzed using exciton theory. The theory was applied to a
      geometric model that reflects the current consensus of the structure of this
      membrane protein [Degli Esposti, M., De Vries, S., Crimi, M., Ghelli, A.,
      Patarnello, T., & Meyer, A. (1993) Biochim. Biophys. Acta 1143, 243-271]. The
      analysis suggests that the iron-iron distance is about 19.5 A, with a possible
      range of 17-23 A; the two hemes appear to be canted at 45 degrees with respect to
      one another. It appears that the two hemes undergo a relative angular
      displacement upon reduction, suggesting some flexibility in the protein
      structure. Some applications of this analysis to other bis-heme proteins are
      considered.

PMID- 8286336
TI  - Glycoforms modify the dynamic stability and functional activity of an enzyme.
AB  - Glycoproteins generally consist of collections of glycosylated variants
      (glycoforms) in which an ensemble of different oligosaccharides is associated
      with each glycosylation site. Bovine pancreatic ribonuclease B occurs naturally
      as a mixture of five glycoforms in which the same polypeptide sequence is
      associated with a series of oligomannose sugars attached at the single N
      glycosylation site. Individual glycoforms were prepared by exoglycosidase
      digestions of RNase B and analyzed directly at the protein level by capillary
      electrophoresis. For the first time, electrophoretically pure single glycoforms
      have been available to explore the possibility that different sugars might
      specifically modify the structure, dynamics, stability, and functional properties
      of the protein to which they are attached. Comparisons of the amide proton
      exchange rates for individual glycoforms of RNase B and unglycosylated RNase A
      showed that while the 3D structure was unaffected, glycosylation decreased
      dynamic fluctuations throughout the molecule. There was individual variation in
      the NH-ND exchange rates of the same protons in different glycoforms,
      demonstrating the effects of variable glycosylation on dynamic stability.
      Consistent with the overall decrease in flexibility, and with the possibility
      that all of the sugars may afford steric protection to susceptible sites, was the
      finding that each of the glycoforms tested showed increased resistance to Pronase
      compared with the unglycosylated protein. In a novel sensitive assay using double
      stranded RNA substrate, the different glycoforms showed nearly a 4-fold variation
      in functional activity; molecular modeling suggested that steric factors may also
      play a role in modulating this interaction.

PMID- 8286338
TI  - Fluorescence investigation of yeast cytochrome c peroxidase oxidation by H2O2 and
      enzyme activities of the oxidized enzyme.
AB  - The role of tryptophan residues as endogenous electron donors in cytochrome c
      peroxidase (CCP) was examined by protein steady-state fluorescence. Compound I
      and more highly oxidized forms of CCP were formed by adding 1, 3, and 10 equiv of
      H2O2 to 5 microM protein at pH 7.0 in the absence of exogenous reducing
      substrates. Addition of native CCP to 8 M urea at pH 1.5 relieved heme quenching,
      and compound I exhibited 90 +/- 4% fluorescence relative to unoxidized CCP,
      consistent with the loss of 0.7 +/- 0.2 tryptophan and the assignment of the
      primary radical site to Trp191. CCP oxidized with 10-fold excess H2O2 exhibited
      65 +/- 1% relative fluorescence, indicating loss of 2.4 +/- 0.1 tryptophans.
      Compound I and the higher oxidized forms of CCP spontaneously decayed to ferric
      CCP species over approximately 24 h with the loss of approximately 0.5 additional
      tryptophan in each case. The 24-h decay product of compound I exhibited 73%
      activity, 74% H2O2 titer, and titration led to the further oxidation of
      approximately 0.6 tryptophan. However, no further tryptophan oxidation was
      observed on titration of the 24-h decay products of samples initially oxidized
      with 3 and 10 equiv of H2O2. These samples exhibited 58 and 18% H2O2 titer, and
      47 and 16% activity, respectively, which shows that radical formation of Trp191
      is not required for activity. The fluorescence decrease with time paralleled the
      decrease in activity of H2O2-oxidized CCP using both ferrocytochrome c and
      ferrocyanide as substrates, indicating that tryptophan and activity loss occurred
      on similar time scales.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286339
TI  - Identification of a metalloprotease from Alzheimer's disease brain able to
      degrade the beta-amyloid precursor protein and generate amyloidogenic fragments.
AB  - A 4.2-kDa polypeptide termed beta protein (A beta) accumulates in senile plaques
      and blood vessels in Alzheimer's disease and Down's syndrome. It is widely
      believed that A beta is the product of the posttranslational processing of a
      larger precursor protein, the beta amyloid precursor protein (APP). The
      proteolytic processes involved in the generation of the A beta are virtually
      unknown. Here the purification and characterization of a protease from
      Alzheimer's disease brain capable of cleaving a 10 amino acid synthetic substrate
      flanking the N terminus of A beta at the Met-Asp bond are described. Most
      importantly, the purified protease degrades human recombinant APP and generates a
      15-kDa amyloidogenic fragment. The protease requires the presence of a reducing
      agent for its activity. Its pH optimum is around physiological pH, while the
      enzyme is inactive at acidic pH (below pH 5.0) and basic pH (over pH 7.6). The
      enzyme is inhibited by N-ethylmaleimide, (hydroxymercuri)benzoate, 1.10
      phenanthroline, EDTA, and EGTA. Phenylmethanesulfonyl fluoride has no effect on
      its activity. This protease is devoid of caseinolytic or gelatinase activities,
      as well as activities against cathepsin B and cathepsin L substrates. Sequence
      analysis reveals high homology to the rat metallopeptidase EC 3.4.24.15, a
      protease involved in neuropeptide processing.

PMID- 8286340
TI  - Structure and function of DNA photolyase.
AB  - Cyclobutane pyrimidine dimers (Pyr < > Pyr) are the major DNA photoproducts
      induced by the UV component of solar radiation. Photoreactivating enzyme (DNA
      photolyase) repairs DNA by utilizing the energy of visible light to break the
      cyclobutane ring of the dimer. Photolyases are monomeric proteins of 50-60 kDa
      with stoichiometric amounts of two noncovalent chromophore/cofactors. One of
      these cofactors is FADH-, and the second chromophore is either
      methenyltetrahydrofolate (MTHF) or 8-hydroxy-5-deazariboflavin (8-HDF). The
      enzyme binds the DNA substrate in a light-independent reaction, the second
      chromophore of the bound enzyme absorbs a visible photon and, by dipole-dipole
      interaction, transfers energy to FADH- which, in turn, transfers an electron to
      Pyr < > Pyr in DNA; the Pyr < > Pyr- splits and back electron transfer restores
      the dipyrimidine and the functional form of flavin ready for a new cycle of
      catalysis.

PMID- 8286341
TI  - Single peptide bond hydrolysis/resynthesis in squash inhibitors of serine
      proteinases. 1. Kinetics and thermodynamics of the interaction between squash
      inhibitors and bovine beta-trypsin.
AB  - The substrate and inhibitory parameters are described for the interaction between
      Cucurbita maxima trypsin inhibitor I (CMTI I) and bovine beta-trypsin. The data
      are fully consistent with the reactive site hypothesis and the standard mechanism
      proposed for the protein inhibitor-serine proteinase interaction. The second
      order association rate constant (k(on)) for the interaction of the intact
      inhibitor and trypsin is high, above 10(6) M-1 s-1. The same value is only 22
      fold lower for the reactive site hydrolyzed inhibitor. This result implicates a
      very low transition-state barrier for the hydrolysis of the Arg5-Ile6 reactive
      site peptide bond. The equilibrium constant Ka (= 1/Km,f) and K(assoc) change by
      6 orders of magnitude in the pH range 4.0-8.3. The steady-state parameters for
      the hydrolysis and resynthesis of the reactive site have been determined over the
      pH range 3.2-8.3. Catalytic rate constants, but not kcat/km, exhibit strong pH
      dependence. The dependence of the hydrolysis constant (Khyd) on pH fits the
      simplest form of the Dobry equation, indicating that after the hydrolysis of the
      reactive site, pK values of any preexistent groups are not perturbed. It is
      suggested that a major factor leading to high kcat/Km values is the presence of
      Arg or Lys residues at the P1 position. Low values of Km result from a
      conservation of the ground-state conformation of the inhibitor binding loop upon
      the complex formation. The crucial stage of the reactive site hydrolysis seems to
      be associated with a change of basic side-chain interactions within the S1
      binding pocket.

PMID- 8286342
TI  - Single peptide bond hydrolysis/resynthesis in squash inhibitors of serine
      proteinases. 2. Limited proteolysis of Curcurbita maxima trypsin inhibitor I by
      pepsin.
AB  - Porcine pepsin hydrolyzes the Leu7-Met8 (P2'-P3') peptide bond in Cucurbita
      maxima trypsin inhibitor I (CMTI I) in the pH range 2.0-4.8. The reaction
      proceeds to equilibrium between intact CMTI I and its cleaved form. The pH
      independent value of the equilibrium constant (Khyd0 = 0.78) indicates that both
      forms of the inhibitor have similar Gibbs energies. The pH dependence of this
      constant shows that the peptide bond hydrolysis does not perturb ionization
      constants of any preexistent groups. The same equilibrium values can also be
      reached from the cleaved inhibitor side through pepsin-catalyzed resynthesis of
      the Leu7-Met8 peptide bond. Catalytic rate constants for the forward (hydrolysis)
      and reverse (resynthesis) reactions are similar. Both catalytic rate constants
      are strongly pH dependent, approaching the highest values at pH 2.0. Michaelis
      constant values for hydrolysis and resynthesis reactions depend much less on pH
      and are within values typical for oligopeptide substrates of pepsin. The
      influence of the binding loop rigidity on slow proteolysis by pepsin and other
      proteinases is discussed.

PMID- 8286343
TI  - Inhibition of glyceraldehyde-3-phosphate dehydrogenase by phosphorylated epoxides
      and alpha-enones.
AB  - Pentalenolactone and koningic acid are antibiotics known for their potent
      inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. The
      reactive groups present in these antibiotics are, respectively, an epoxide and an
      alpha-enone, which form covalent bonds with an active-site cysteine residue of
      the enzyme. This information was used for the design of two series of
      glyceraldehyde 3-phosphate analogues with similar reactive groups that could
      function as potential irreversible inhibitors of glyceraldehyde-3-phosphate
      dehydrogenase. Inactivation kinetics, NMR analysis, protection experiments, and
      titration of free cysteine residues together indicate that the inhibitors bind to
      the active site of the enzyme and form a covalent bond with the active-site
      cysteine residue of the enzyme. Binding probably takes place at the inorganic
      phosphate site of the enzyme and may lead to a conformational change. Comparison
      of the reactivities of the inhibitors for the glycosomal enzyme from the
      protozoan parasite Trypanosoma brucei and the rabbit muscle enzyme revealed that
      some of them had a preference for the trypanosome enzyme. When their effect was
      measured on the multiplication of trypanosome in vitro cultures, one inhibitor
      appeared to exhibit an inhibitory effect at a concentration significantly lower
      than the trypanocidal drugs, pentamidin and (difluoromethyl)ornithine, that are
      routinely used in the treatment of African sleeping sickness.

PMID- 8286344
TI  - Variants of subtilisin BPN' with altered specificity profiles.
AB  - A strategy for increasing the size of the S4 binding pocket was used to improve
      the specificity of subtilisin BPN' toward substrates with large hydrophobic P4
      side chains. This approach involves single and double amino acid replacements at
      positions 104, 107, and 126. Previously, alteration of I107 to glycine has been
      found to increase the specificity of subtilisin toward leucine, isoleucine, and
      phenylalanine as P4 residues by up to 214-fold. Replacement of Y104 by alanine
      also yields a similar improvement in specificity. However, this subtilisin
      variant favors isoleucine and phenylalanine over leucine. When L126 was replaced
      by valine, alanine, and glycine, respectively, only the L126A subtilisin variant,
      which possesses a 28-fold-increased catalytic efficiency for isoleucine compared
      with all other substrates tested, showed a significantly improved specificity
      profile. As inferred from the double-mutant enzymes I107G/L126V, I107G/L126A, and
      I107G/Y104A, none of the effects of the single amino acid replacements on the
      kinetic parameters are additive. The I107G/L126V mutant subtilisin has the
      largest improvement in P4 substrate specificity reported so far: kcat/KM is
      increased 340-fold for leucine compared to alanine. By contrast, the specificity
      profile of the I107G/Y104A mutant enzyme is impaired in comparison with that of
      the corresponding single mutants. Therefore, the design of high-specificity
      subtilisin variants through the combination of single amino acid replacements in
      the S4 pocket appears to be nontrivial due to the interference of the introduced
      structural changes.

PMID- 8286345
TI  - Oxygen-18 kinetic isotope effects in the dopamine beta-monooxygenase reaction:
      evidence for a new chemical mechanism in non-heme metallomonooxygenases.
AB  - Previous studies of dopamine beta-monooxygenase (D beta M) have implicated the
      formation of a substrate-derived benzylic radical via a hydrogen atom abstraction
      mechanism [Miller & Klinman (1985) Biochemistry 24, 2114]. We now address the
      nature of the oxygen species catalyzing C-H bond cleavage through the measurement
      of oxygen-18 isotope effects as a function of substrate structure. Using
      deuterium isotope effects, together with experimental O-18 isotope effects with
      protonated and deuterated substrates, it has been possible to calculate intrinsic
      O-18 isotope effects. Since the D beta M mechanism includes many steps which may
      involve changes in bond order at dioxygen, e.g., the reversible binding of O2 to
      the active-site copper and its reductive activation to a copper-hydroperoxide
      species, the intrinsic O-18 isotope effect is expected to be the product of two
      terms: (1) an overall equilibrium O-18 isotope effect on steps leading from O2
      binding to the formation of the intermediate which catalyzes C-H bond cleavage
      and (2) a kinetic O-18 isotope effect on the C-H bond cleavage step. Thus, the
      magnitude of a single O-18 isotope effect measurement cannot reveal the nature of
      the bonding at oxygen during substrate activation. In the present study we have
      measured the change in O-18 isotope effect as a function of substrate structure
      and reactivity, finding values of 18(V/K) which decrease from 1.0281 +/- 0.001 to
      1.0216 +/- 0.0003 as the rate of the C-H bond cleavage step decreases from 680 to
      2 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286346
TI  - Crystallographic studies of two alcohol dehydrogenase-bound analogues of thiazole
      4-carboxamide adenine dinucleotide (TAD), the active anabolite of the antitumor
      agent tiazofurin.
AB  - Thiazole-4-carboxamide adenine dinucleotide (TAD) is the active anabolite of the
      antitumor drug tiazofurin. Beta-methylene TAD (beta-TAD) is a phosphodiesterase
      resistant analogue of TAD, active in tiazofurin-resistant cells. Beta-methylene
      SAD (beta-SAD) is the active selenium derivative of beta-TAD. Both agents are
      analogues of the cofactor NAD and are capable of acting as general dehydrogenase
      inhibitors. Crystal structures of beta-TAD and beta-SAD bound to horse liver
      alcohol dehydrogenase (LADH) are presented at 2.9 and 2.7 A, respectively. Both
      complexes crystallize in the orthorhombic space group C222(1) and are isomorphous
      to apo-LADH. Complexes containing beta-TAD and beta-SAD were refined to
      crystallographic R values of 15% and 16%, respectively, for reflections between 8
      A and the minimum d spacing. Conformations of both inhibitors are similar. beta
      TAD and beta-SAD bind to the "open" form of LADH in the normal cofactor-binding
      cleft between the coenzyme and catalytic domains of each monomer. Binding at the
      adenosine end of each inhibitor resembles that of NAD. However, the positions of
      the thiazole and selenazole heterocycles are displaced away from the catalytic Zn
      cation by approximately 4 A. Close intramolecular S-O and Se-O contacts observed
      in the parent nucleoside analogues are maintained in both LADH-bound beta-TAD and
      beta-SAD, respectively. These conformational constraints may influence the
      binding specificity of the inhibitors.

PMID- 8286347
TI  - Regiospecificity of the hydrolysis of diadenosine polyphosphates catalyzed by
      three specific pyrophosphohydrolases.
AB  - The different patterns of enzymatic cleavage of diadenosine polyphosphates,
      ApnAs, where n = 3-5, have been established by fast atom bombardment mass
      spectrometry, FAB MS, of the nucleotide products formed in the presence of
      H2(18)O. The three specific pyrophosphohydrolases, Ap3A hydrolase (EC 3.6.1.29)
      and (asymmetrical) Ap4A hydrolase (EC 3.6.1.17) from lupin and the (symmetrical)
      Ap4A hydrolase (EC 3.6.1.41) from Escherichia coli, manifest three different
      regiospecificities. The Ap3A hydrolase cleaves all four substrates tested, Ap3A,
      Ap4A, ApCH2ppA, and ApCHFppA, to give [18O]AMP and the corresponding unlabeled
      adenosine nucleotide. In each case, the enzyme cleaves at the phosphate proximate
      to the bound adenosine moiety. The (asymmetrical) Ap4A hydrolase cleaves both
      Ap4A and Ap5A to give unlabeled ATP plus [18O]AMP and [18O]ADP, respectively, and
      is thus seen to add water at the fourth phosphate from the bound adenosine
      moiety. Lastly, the (symmetrical) Ap4A hydrolase from E. coli gives beta-[18O]ADP
      from Ap3A, Ap4A, and Ap5A along with the unlabeled nucleotide coproducts. In
      addition, with Ap4A alpha S (ApspppA) as substrate for the bacterial enzyme, the
      products are beta-[18O]ADP and unlabeled ADP alpha S. This symmetrical enzyme is
      thus characterized as cleaving the polyphosphate chain at the second phosphate
      from the bound adenosine moiety.

PMID- 8286348
TI  - Lipopolysaccharides of Campylobacter jejuni serotype O:19: structures of core
      oligosaccharide regions from the serostrain and two bacterial isolates from
      patients with the Guillain-Barre syndrome.
AB  - Lipopolysaccharides from phenol-water extraction of cells of Campylobacter jejuni
      serotype O:19 were separated into a water-soluble gel of low M(r) and a water
      soluble component of high M(r). Acetic acid hydrolysis of the ketosidic linkages
      to lipid A furnished respectively a core oligosaccharide, the structure of which
      is reported herein, and an O antigenic polysaccharide. Structural investigations
      were performed on the O-deacetylated lipopolysaccharide of low M(r), the
      liberated core oligosaccharide and the various products from removal of
      neuraminic acid and phosphate residues, and from the Smith degradation. It is
      concluded that the lipopolysaccharide from the serostrain has a core region with
      two types of closely related oligosaccharide chains showing striking homologies
      with gangliosides, the first with a single N-acetylneuraminic acid residue in an
      outer chain resembling GM1 and the second with two N-acetyl-neuraminic acid
      residues with a terminal region resembling GD1a. Similar experiments were carried
      out on lipopolysaccharides of low M(r) from bacterial isolates OH 4384 and OH
      4382 serotyped as O:19 that had been obtained from two patients who subsequently
      developed the Guillain-Barre syndrome. The core oligosaccharide region of
      lipopolysaccharide from the former isolate differed only slightly from that of
      the serostrain, whereas that from the latter isolate was distinctly shorter.

PMID- 8286349
TI  - Role of the amino-terminal domain in regulating interactions of annexin I with
      membranes: effects of amino-terminal truncation and mutagenesis of the
      phosphorylation sites.
AB  - Phosphorylation of the N-terminal tail by protein kinase C strongly inhibits the
      ability of bovine or human annexin I to aggregate chromaffin granules by
      increasing the calcium requirement 4-fold (Wang, W., & Creutz, C. E. (1992)
      Biochemistry 31, 9934-9936). In the present study three forms of human annexin I
      truncated in the amino terminus at residue Trp-12, Lys-26, or Lys-29 exhibit
      dramatic differences in their sensitivities to calcium in a chromaffin granule
      aggregation assay, while the [Ca2+](1/2)max values for binding of the truncated
      proteins to granule membranes are similar. Cleavage at Trp-12 causes a 3-fold
      decrease in calcium sensitivity in the membrane aggregation assay, while cleavage
      at Lys-26 causes a 4-fold enhancement of calcium sensitivity. In contrast,
      cleavage at Lys-29 results in virtually no change in calcium sensitivity.
      Mutagenic substitution with negatively charged amino acids of Ser-27, a site for
      phosphorylation by protein kinase C, or Tyr-21, a site for phosphorylation by the
      epidermal growth factor receptor kinase, mimics the inhibition of granule
      aggregating activity seen with phosphorylation by protein kinase C. When bovine
      chromaffin cells are stimulated to secrete by nicotine, annexin I is
      phosphorylated in the amino terminus. Thr-24 and Ser-28, which are sites for
      phosphorylation by protein kinase C in vitro, are two of the sites phosphorylated
      in vivo in stimulated chromaffin cells. These data demonstrate that the ability
      of annexin I to promote membrane aggregation is highly sensitive to changes in
      the structure of the N-terminal domain of the protein.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8286350
TI  - Down-regulation of hepatic HMG-CoA reductase in mice by dietary cholesterol:
      importance of the delta 5 double bond and evidence that oxidation at C-3, C-5, C
      6, or C-7 is not involved.
AB  - It has been suggested that the down-regulation of hepatic HMG-CoA reductase by
      dietary cholesterol requires modification of the cholesterol molecule before it
      can exert its suppressive action. In a recent study [Lund, E., Breuer, O., &
      Bjorkhem, I. (1992) J. Biol. Chem. 267, 25092-25097], we showed that side-chain
      hydroxylation is not likely to be of importance for this down-regulation in male
      C57BL/6J mice. In this study, we studied the possibility that modification of
      cholesterol in the region around the delta 5 double bond is required for the
      suppression. It was shown that cholestanol, which does not have a delta 5 double
      bond but is otherwise identical to cholesterol, is a poor suppressor of HMG-CoA
      reductase activity. Groups of mice were fed with diets containing cholestanol,
      epicholesterol, 6-methylcholesterol, 6-fluorocholesterol, [3 alpha
      2H]cholesterol, and [7,7-2H2]cholesterol with control groups fed cholesterol or a
      cholesterol-free diet. These cholesterol analogues were selected to interfere
      with potential in vivo modifications and to clarify structural requirements for
      the down-regulation. After sacrifice, the hepatic HMG-CoA reductase activity was
      assayed. Cholesterol, 6-methylcholesterol, and 6-fluorocholesterol were efficient
      suppressors whereas cholestanol and epicholesterol only had a low suppressive
      capacity. Differences in the degree of absorption from the intestine or degree of
      esterification were too small to explain the differences in HMG-CoA reductase
      suppressing capacity. The two deuterated cholesterol species had a suppressive
      capacity similar to that of unsubstituted cholesterol.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8286351
TI  - Surface charge of bacteriorhodopsin detected with covalently bound pH indicators
      at selected extracellular and cytoplasmic sites.
AB  - We present a method that allows the detection of the surface charge density of
      bacteriorhodopsin (bR) at any selected protein surface site. The optical pH
      indicator fluorescein was covalently bound to the sulfhydryl groups of single
      cysteine residues, which were introduced at selected positions in bR by site
      directed mutagenesis. On the extracellular side, the positions were in the BC
      loop (72) and in the DE loop (129-134). On the cytoplasmic side, one position in
      each loop was labeled: 35 (AB), 101 (CD), 160 (EF), and 231 (carboxy tail). The
      apparent pKs of fluorescein in these positions were determined for various salt
      concentrations. The local surface charge density was calculated from the
      dependence of the apparent pK of the dye on the ionic strength using the Gouy
      Chapman equation. The surface charge density at pH 6.6 is more negative on the
      cytoplasmic side (averaged over all positions, -2.5 +/- 0.2 elementary charges
      per bR) than on the extracellular side (average, -1.8 +/- 0.2 elementary charges
      per bR) with little variation along the surface. Since the experiments were
      performed with electrically neutral CHAPS/DMPC micelles, these values represent
      the charge present on bR itself.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286352
TI  - The cardiac Na(+)-Ca2+ exchanger: relative rates of calcium and sodium movements
      and their modulation by protonation-deprotonation of the carrier.
AB  - The exchange cycle of the cardiac Na(+)-Ca2+ exchanger can be described as
      separate steps of Ca2+ and Na+ transport [Khananshvili, D. (1990) Biochemistry
      29, 2437-2442]. In order to determine the relative rates of Na+ and Ca2+ movement
      during the Na(+)-Ca2+ and Ca(2+)-Ca2+ exchange modes, the ratios (R) of Na(+)
      Ca2+/Ca(2+)-Ca2+ exchanges were estimated with saturating concentrations of ions
      at both sides of the membrane. The effect of extravesicular pH and voltage
      (potassium valinomycin) on the initial rates (t = 1 s) of Na(+)-Ca2+ and Ca(2+)
      Ca2+ exchange were investigated by assuming that, under the conditions tested,
      the intravesicular pH (pH 7.4) is not affected. Na(+)- or Ca(2+)-preloaded
      sarcolemma vesicles were diluted rapidly in assay medium containing 45Ca and
      buffer (pH 5.0-10.9), and the reaction of 45Ca uptake was quenched by using a
      semi-rapid-mixing device. Under conditions in which [45Ca]o = [Ca]i = 250 microM,
      the pH-dependent curve of Ca(2+)-Ca2+ exchange shows a bell shape in the acidic
      range (pKa1 = 5.1 +/- 0.1 and pKa2 = 6.5 +/- 0.2) followed by activation of the
      exchange in the alkaline range (pKa3 = 10.0 +/- 0.2). With [45Ca]o = 250 microM
      and [Na]i = 160 mM, the Na(+)-Ca2+ exchange increases monotonically from pH 5.0
      to 9.5 (pKa1 = 5.1 +/- 0.1, pKa2 = 7.2 +/- 0.2, and pKa3 = 9.1 +/- 0.2). At pH <
      6.1, the ratio of Na(+)-Ca2+/Ca(2+)-Ca2+ exchange is close to unity (R
      approximately 1), while it increases to R = 3-4 in the range of pH 7.1
      9.3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286353
TI  - Conformation of phosphatidylserine in bilayers as studied by Fourier transform
      infrared spectroscopy.
AB  - The 13C labeled lipid 1[1'-13C]DPPS-NH4+ and its metal salts were used to
      unambiguously assign all carbonyl vibrations in the infrared spectrum of
      phosphatidylserines. It is shown that the C=O stretching band at 1741 cm-1 of
      phosphatidylserines previously assigned to the sn-1 C = O vibration contains
      contributions from both the sn-1 and the sn-2 carbonyls. The C=O stretching band
      at frequencies between 1715 and 1730 cm-1 previously assigned to the sn-2 C=O
      vibration also contains contributions from both carbonyl groups. The frequency
      dependence observed with the ester carbonyls primarily reflects hydrogen bonding
      and the polarity of the immediate vicinity. Conformational changes are accounted
      for in terms of frequency shifts if the conformational change involves the
      disposition of the C=O groups and in turn the hydrogen bonding properties. The
      infrared spectra of phospholipids dispersed in aqueous medium in the liquid
      crystalline state are inconsistent with a simple phospholipid conformation, e.g.,
      with a conformation as found in the single-crystal structure of 1,2-dimyristoyl
      sn-phosphatidylcholine and 1,2-dilauroyl-rac-phosphatidylethanolamine. The
      spectra support the hypothesis proposed earlier (Hauser et al., Biochemistry,
      1988) on the basis of existing single-crystal phospholipid structures and NMR
      evidence. The hypothesis states that several conformations are present in liquid
      crystalline phospholipid dispersions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286354
TI  - Vaccinia DNA topoisomerase I: single-turnover and steady-state kinetic analysis
      of the DNA strand cleavage and ligation reactions.
AB  - Vaccinia DNA topoisomerase I catalyzes a reversible, site-specific strand
      cleavage and resealing reaction with duplex DNA involving a transient 3'
      phosphotyrosyl linkage between the DNA and Tyr-274 of the enzyme. Single-turnover
      and steady-state kinetic measurements, as well as DNA binding studies with DNA
      duplexes containing the preferred cleavage sequence (5'-CCCTT decreases -3') in
      50 mM Tris-HCl, pH 7.5, at 20 degrees C, have permitted the evaluation of the
      individual rate constants for strand cleavage (kcl) and religation (kr) and for
      duplex DNA binding and dissociation. The values of kcl = 0.07 s-1 and kr = 0.66 s
      1 indicate that the internal cleavage equilibrium (Kcl = kcl/kr = 0.1) favors the
      uncleaved E.DNA complex. The apparent second-order rate constant kcl/KmDNA + = 8
      x 10(5) M-1 s-1 for the single-turnover cleavage reaction is 10(2)-10(3)-fold
      less than the rate of diffusional encounter and provides an estimate of k(on)
      (DNA). Single-turnover cleavage experiments using a duplex substrate with a
      nonbridging racemic phosphorothioate nucleotide substitution at the cleavage site
      showed biphasic cleavage kinetics with equal amplitudes for each phase, which was
      fit to a double exponential: kfast = 0.01 s-1 and kslow = 0.0004 s-1. These "thio
      effects" (= kclphos/kclthiol) of 4.6- and 115-fold indicate that cleavage is at
      least partially rate-limiting in the single-turnover reaction; the two kinetic
      phases indicate a strong preference for cleavage of one thio isomer. Multiple
      turnover cleavage-religation reactions showed an initial pre-steady-state burst
      proportional to enzyme, followed by a slower steady-state rate with a value of
      kcat = 0.006 s-1. The phosphorothioate substrate showed a smaller burst and no
      significant thio effect on kcat. These results indicate fast chemical steps and
      largely rate-limiting dissociation of the religated product (KD = 54 nM) in the
      steady-state, a conclusion confirmed by direct measurement of the rate constant
      for product dissociation as 0.01 s-1. MgCl2 (5 mM) increases this rate constant
      by an order of magnitude, thus explaining the divalent cation induced
      acceleration of DNA supercoil relaxation by this enzyme. No divalent cation
      binding by the enzyme was detected indicating this effect to result from metal
      binding to DNA. The rate constants kcl and kr for the nucleophilic attack of Tyr
      274 and deoxyribose 5'-OH at phosphorus represent approximately 10(9)- and 10(12)
      fold enhancements over the analogous attack of phenolate and alcoholate anions at
      the phosphorus backbone of DNA in solution at pH 7.5. Consistent with this
      estimate, the Y274F mutant is at least 10(6)-fold less active in cleavage than
      the wild-type enzyme.

PMID- 8286355
TI  - Structural analysis of peptide fragment 71-93 of transthyretin by NMR
      spectroscopy and electron microscopy: insight into amyloid fibril formation.
AB  - A peptide corresponding to the amino acid region 71-93 of the plasma protein
      transthyretin (TTR) has been synthesized to investigate its role in the native
      folding of the molecule and the possible relationship between mutations in this
      region and amyloid formation of TTR. In the native structure this fragment
      includes a beta-strand followed by a short helix and turns back on itself to form
      part of an antiparallel beta-sheet. Electron microscopy has shown that the
      peptide is not intrinsically amyloidogenic. NMR spectroscopy has been used to
      investigate the conformational dependency of the peptide on the solution
      conditions. Minor populations of peptide showing partial turns were apparent in
      deuterated dimethyl sulfoxide (DMSO-d6). Some indication of nascent helix between
      residues 5 and 12 was observed in water, and upon the addition of 20%
      trifluoroethanol (TFE) the span of helix was confirmed. The intrinsic tendency to
      form a helical structure between residues 5 and 12 in solution suggests that the
      helical region, also present in the native crystallographically determined TTR
      structure at corresponding residues 75-82, is an important folding initiation
      site. In contrast, the beta-sheet motif observed in the native structure was not
      detected in solution. It is proposed that mutations in TTR occurring in the
      helical region result in subtle changes in the TTR structure leading to amyloid
      fibril formation.

PMID- 8286356
TI  - DNase I hypersensitive sites in promoter elements associated with basal and
      vitamin D dependent transcription of the bone-specific osteocalcin gene.
AB  - Nuclease hypersensitive sites were mapped in the proximal promoter of the
      osteocalcin gene, which is expressed only in bone cells exhibiting the mature
      osteoblast phenotype. Nuclei from proliferating and confluent rat osteosarcoma
      (ROS) 17/2.8 cells were subjected to DNase I digestion, and hypersensitivity was
      assayed by the indirect end-labeling method, using osteocalcin gene probes.
      Hypersensitive sites were detected in two promoter domains: -590 to -390, which
      spans the vitamin D responsive element, and -170 to -70, which spans the TATA box
      and the CCAAT-containing OC box domain. Together, these elements regulate basal
      and vitamin D enhanced osteocalcin gene transcription. We observed a parallel
      relationship between the intensity of bands representing the hypersensitive sites
      and the extent to which the osteocalcin gene is transcribed. Both in confluent
      cultures and in response to vitamin D, when osteocalcin transcription was
      upregulated, the hypersensitive bands were significantly intensified.
      Additionally, the bands were decreased under conditions that downregulate
      osteocalcin gene transcription. A functional relationship between the presence of
      hypersensitive sites and osteocalcin gene transcription is further supported by
      the absence of hypersensitivity in nonosseous cells that do not express
      osteocalcin, although these proliferating cells exhibited hypersensitivity in a
      cell cycle regulated histone gene promoter. Our results suggest the involvement
      of chromatin structure in transcriptional responsiveness of the osteocalcin gene
      to physiologic modulation.

PMID- 8286357
TI  - Solution structure of the octamer motif in immunoglobulin genes via restrained
      molecular dynamics calculations.
AB  - The solution structure of the DNA decamer d(CATTTGCATC)-d(GATGCAAATG), comprising
      the octamer motif of immunoglobulin genes, is determined by restrained molecular
      dynamics (rMD) simulations. The restraint data set includes interproton distances
      and torsion angles for the deoxyribose sugar ring which were previously obtained
      by a complete relaxation matrix analysis of the two-dimensional nuclear
      Overhauser enhancement (2D NOE) intensities and by the quantitative simulation of
      cross-peaks in double-quantum-filtered correlated (2QF-COSY) spectra. The
      influence of torsion angles and the number of experimental distance restraints on
      the structural refinement has been systematically examined. Omitting part of the
      experimental NOE-derived distances results in reduced restraint violations and
      lower R factors but impairs structural convergence in the rMD refinement. Eight
      separate restrained molecular dynamics simulations were carried out for 20 ps
      each, starting from either energy-minimized A- or B-DNA. Mutual atomic root-mean
      square (rms) differences among the refined structures are well below 1 A and
      comparable to the rms fluctuations of the atoms about their average position,
      indicating convergence to essentially identical structures. The average refined
      structure was subjected to an additional 100 ps of rMD simulations and analyzed
      in terms of average torsion angles and helical parameters. The B-type duplex
      exhibits clear sequence-dependent variations in its geometry with a narrow minor
      groove at the T3.A3 tract and a large positive roll at the subsequent TG.CA step.
      This is accompanied by a noticeable bend of the global helix axis into the major
      groove. There is also evidence of significant flexibility of the sugar-phosphate
      backbone with rapid interconversion among different conformers.

PMID- 8286358
TI  - Binding specificity of a nuclear scaffold: supercoiled, single-stranded, and
      scaffold-attached-region DNA.
AB  - Scaffold-attached-region (SAR) elements of DNA enhance transcriptional rates, and
      this has been correlated with their ability to undergo separation into single
      strands (ssDNA) under conditions of negative superhelicity (Bode et al., 1992).
      The competition studies presented here suggest that the SAR-scaffold interaction
      is based, in part, on the recognition of single strands, while about one-half of
      SAR sites are inaccessible to ssDNA. Conversely, since there are 20,000 SAR sites
      but more than 60,000 sites for ssDNA per nuclear equivalent, not all ssDNA sites
      are open for SARs. In addition, a completely separate set of binding centers
      recognizing and enzymatically converting DNA of superhelical density below -0.04
      can be titrated. These findings reflect multiple binding specificities for
      scaffold preparations that are routinely used for screening scaffold-attached
      regions.

PMID- 8286359
TI  - Factors influencing the extent and regiospecificity of cross-link formation
      between single-stranded DNA and reactive complementary oligodeoxynucleotides.
AB  - Cross-link formation, within the duplex, by oligodeoxynucleotides containing a 5
      [omega-(omega-haloacylamido)alkyl]-2'-deoxyuridine to a complementary
      oligodeoxynucleotide was investigated under conditions approximating the
      physiologic environment. The site and extent of crosslinking to the target strand
      were determined for several electrophilic haloacylamidoalkyl structures. The
      regiospecificity of alkylation was primarily determined by the length of the
      electrophilic haloacylamidoalkyl group, while the extent of reaction was
      dependent upon both the structure of the acylamidoalkyl group and the reactivity
      of the electrophile. Cross-linking was additionally modulated by the sequence of
      the duplex in the vicinity of the alkylation site. The exact placement of the
      electrophile adjacent to the targeted nucleophile, an N-7 group on a specific
      guanine base in the target strand, was the most important factor in determining
      the rate of reaction. With the optimal haloacylamidoalkyl structure and duplex
      sequence, the most rapid rate obtained was t1/2 = 1.3 h at 37 degrees C.

PMID- 8286360
TI  - Preferential binding of H1e histone to GC-rich DNA.
AB  - We have investigated the binding of a pure H1 histone, the mouse variant H1e, to
      a 214 bp fragment of DNA from pBR322. Binding was monitored by observing the
      effects of the protein on melting of the DNA and by a gel-mobility-shift assay.
      We found, using this highly purified system, that H1e protein binds
      preferentially and cooperatively to the GC-rich region of the DNA. A chemically
      synthesized peptide containing 25 residues, corresponding to a region of the
      carboxyl-terminal domain of H1e, shows the same sequence preference but does not
      exhibit cooperativity.

PMID- 8286361
TI  - Solution structure of RP 71955, a new 21 amino acid tricyclic peptide active
      against HIV-1 virus.
AB  - The structure of RP 71955, a new tricyclic 21 amino acid peptide active against
      human immunodeficiency virus 1, was determined. Its amino acid composition was
      inferred from the results of fast atom bombardment mass spectrometry, nuclear
      magnetic resonance, Raman spectroscopy, and amino acid analysis. Its sequence
      could not be determined classically, using Edman degradation, given the lack of a
      free terminal NH2. It was deduced from the interpretation of interresidue nuclear
      Overhauser effects and confirmed by the sequencing of peptides obtained by
      limited chemical hydrolysis. It was found to be CLGIGSCNDFAGCGYAVVCFW. An
      internal amide bond between the NH2 of C1 and the gamma-COOH of D9 was observed,
      as well as two disulfide bridges, one between C1 and C13 and one between C7 and
      C19. The three-dimensional structure of RP 71955 was determined from nuclear
      magnetic resonance derived constraints using distance geometry, restrained
      molecular dynamics, nuclear Overhauser effect back calculation, and an iterative
      refinement using a full relaxation matrix approach. Analogies between the
      structure of RP 71955 and some functional domains of gp41, the transmembrane
      protein of human immunodeficiency virus 1, suggest hypotheses concerning the mode
      of action of RP 71955.

PMID- 8286362
TI  - Inhibition of thermolysin and neutral endopeptidase 24.11 by a novel glutaramide
      derivative: X-ray structure determination of the thermolysin-inhibitor complex.
AB  - Determination of the X-ray structure of thermolysin-inhibitor complexes has
      proven useful in aiding our understanding of the mode of binding of inhibitors of
      related, physiologically important, mammalian zinc peptidases including neutral
      endopeptidase EC 3.4.24.11 and angiotensin-converting enzyme. Here we describe
      the mode of binding to crystalline thermolysin of N-[1-(2(R,S)-carboxy-4
      phenylbutyl)-cyclopentylcarbonyl]-(S) -tryptophan (CCT). CCT is an analogue of
      both candoxatrilat, a potent inhibitor of neutral endopeptidase 24.11, and of the
      5-indanyl ester prodrug candoxatril, which is under clinical evaluation as a
      potential therapy for congestive heart failure. CCT differs from the previously
      studied N-carboxyalkyl dipeptide CLT [N-(S)-(1-carboxy-3-phenylpropyl)-(S)-leucyl
      (S)-tryptophan] in several important respects. It has a highly constrained gem
      cyclopentyl P1' substituent and lacks the characteristic imino nitrogen
      substituent of CLT. The structure determination shows that, notwithstanding the
      conformational influence of the gem-cyclopentyl substituent, CCT binds within the
      active site of thermolysin in a similar manner to CLT. Although the
      characteristic hydrogen bond between the imino nitrogen of CLT and thermolysin is
      absent in CCT, the affinities of the two inhibitors for the enzyme are virtually
      identical. These results illustrate the importance of considering not only those
      hydrogen bonds that are formed in an enzyme-ligand complex but also the other
      hydrogen bonds that may be lost due to desolvation of the enzyme and ligand on
      formation of the complex. In addition, the overall conformational demands placed
      upon a ligand in order to achieve receptor interaction may be critically
      important.

PMID- 8286363
TI  - Nuclear magnetic resonance study of the interaction of T4 endonuclease V with
      DNA.
AB  - T4 endonuclease V catalyzes the DNA strand cleavage in the vicinity of a thymine
      dimer. In order to obtain insight into the specific recognition mechanism of this
      enzyme with a thymine photodimer within DNA, the conformations of five different
      DNA duplexes, [sequence: see text] with which the enzyme can interact, were
      studied by 1H NMR. DNA I, DNA IV, and DNA V do not contain the TT sequence or a
      thymine dimer and hence, are expected to bind the enzyme only in a nonspecific
      manner. DNA II includes a single TT sequence which does not form a thymine dimer.
      Only DNA III is expected to bind specifically to the enzyme through a thymine
      photodimer. The NMR spectra of these five DNA duplexes in the absence of the
      enzyme clearly show that the formation of a thymine dimer within the DNA induces
      only a minor distortion in the structure and that the overall structure of B-type
      DNA is retained. The photodimer formation is found to cause a large change in
      chemical shifts at the GC7 base pair, which is located at the 3'-side of the
      thymine dimer, accompanied by the major conformational change at the thymine
      dimer site. The effects of T4 endonuclease V binding on these DNA duplexes were
      also investigated by 1H NMR. The binding of this enzyme to DNA I, DNA IV, and DNA
      V causes no alteration in chemical shift values of the imino proton resonances,
      but the binding to DNA II induces a small downfield shift in the imino proton
      resonance of GC7.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286364
TI  - Site-directed mutagenesis, fluorescence, and two-dimensional NMR studies on
      microenvironments of effector region aromatic residues of human c-Ha-Ras protein.
AB  - The Tyr residues in positions 32 and 40 of human c-Ha-Ras protein were replaced
      by site-directed mutagenesis (Y32F, Y32W, Y40K, and Y40W) to examine their roles
      in the signal-transducing activity and the sensitivity to the GTPase activating
      protein (GAP). The signal-transducing activity of the oncogenic Ras protein in
      PC12 cells was lost upon mutations Y32F and Y40K, but retained upon mutations
      Y32W and Y40W. These results suggest that residues 32 and 40 are both required to
      have aromatic groups and residue 32 is further required to have a hydrogen donor.
      On the other hand, three mutations (Y32F, Y32W, and Y40W) caused no appreciable
      reduction in either GAP-binding affinity or GAP sensitivity. By the Y40K
      mutation, GAP-binding affinity was slightly lowered, while GAP sensitivity was
      drastically impaired. Therefore, for residues 32 and 40 of Ras, interactions with
      GAP appear to be different from those with the target of signal transduction in
      the PC12 cell. As for the Y32W-Ras protein bound with an unhydrolyzable GTP
      analogue (GMPPNP), the Trp32 fluorescence is appreciably red-shifted, weaker, and
      more susceptible to KI quenching as compared to that of the GDP-bound form. Two
      dimensional NMR spectroscopy with selectively deuterated Ras proteins revealed
      fewer and weaker nuclear Overhauser effects on the aromatic protons of Trp32 in
      the GMPPNP-bound form than in the GDP-bound form. This indicates that the side
      chain of Trp32 is more exposed to the solvent in the GMPPNP-bound form than in
      the GDP-bound form.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286365
TI  - 13C NMR analysis of intercompartmental flow of one-carbon units into choline and
      purines in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the three-carbon of serine is normally the major one
      carbon donor, although glycine and formate can substitute for serine. The second
      carbon of glycine enters via the glycine cleavage system in the mitochondria and
      can satisfy all cellular one-carbon requirements. It remains unresolved, however,
      as to the route by which these mitochondrial one-carbon units supply cytosolic
      anabolic processes. In the present work, we have used yeast mutants blocked at
      selected sites and 13C NMR to trace the incorporation of glycine-derived
      mitochondrial 5,10-methylenetetrahydrofolate into nonmitochondrial synthesis of
      choline and purines. Label incorporation into choline traces the methylation
      pathway of choline synthesis from production of serine to methylation of
      phosphatidylethanolamine. The active one-carbon unit of S-adenosylmethionine
      involved in methylation reactions originates almost solely from C3 of serine. On
      the other hand, flow of mitochondrial one-carbon units to 10
      formyltetrahydrofolate for purine synthesis is shown to occur via both serine and
      formate. Formate transport accounts for at least 25% of the total, even during
      growth with sufficient serine to provide for the one-carbon requirements of the
      cell. This work shows that the synthetase function of the cytosolic C1
      tetrahydrofolate synthase plays a critical role in the processing of
      mitochondrial one-carbon units to 10-formyltetrahydrofolate pools. In addition,
      this study provides evidence of two pools of glycine within the mitochondria and
      establishes a system of analyzing flux into the different folate derivatives.

PMID- 8286366
TI  - Cutinase, a lipolytic enzyme with a preformed oxyanion hole.
AB  - Cutinases, a group of cutin degrading enzymes with molecular masses of around 22
      25 kDa (Kolattukudy, 1984), are also able to efficiently hydrolyse triglycerides
      (De Geus et al., 1989; Lauwereys et al., 1991), but without exhibiting the
      interfacial activation phenomenom (Sarda et al., 1958). They belong to a class of
      proteins with a common structural framework, called the alpha/beta hydrolase fold
      (Martinez et al., 1992; Ollis et al., 1992). We describe herein the structure of
      cutinase covalently inhibited by diethyl-p-nitrophenyl phosphate (E600) and
      refined at 1.9-A resolution. Contrary to what has previously been reported with
      lipases (Brzozowski et al., 1991; Derewenda et al., 1992; Van Tilbeurgh et al.,
      1993), no significant structural rearrangement was observed here in cutinase upon
      the inhibitor binding. Moreover, the structure of the active site machinery,
      consisting of a catalytic triad (S120, H188, D175) and an oxyanion hole (Q121 and
      S42), was found to be identical to that of the native enzyme, whereas the
      oxyanion hole of Rhizomucor lipase (Brzozowski et al., 1991; Derewenda et al.,
      1992), like that of pancreatic lipase (van Tilbeurgh et al., 1993), is formed
      only upon enzyme-ligand complex formation. The fact that cutinase does not
      display interfacial activation cannot therefore only be due to the absence of a
      lid but might also be attributable to the presence of a preformed oxyanion hole.

PMID- 8286367
TI  - Dissociation and association of the HIV-1 protease dimer subunits: equilibria and
      rates.
AB  - The kinetics and equilibrium properties were investigated for the interconversion
      between the active dimer of human immunodeficiency virus 1 (HIV-1) protease and
      its inactive monomeric subunits. The equilibrium dissociation constant (Kd) of
      the dimeric protease as well as the monomer association rate were obtained by
      monitoring the fluorescence change of an active-site-directed fluorescent probe
      (L-737244) upon its binding to the protease. The Kd of the HIV-1 protease is
      strongly pH dependent. At pH 5.5 where the enzyme is most active catalytically,
      the extrapolated values of Kd are 0.75 and 3.4 nM at 30 and 37 degrees C,
      respectively. The rate constant for HIV-1 monomer association, approximately 4 x
      10(5) M-1 s-1, is within the range commonly observed for protein-protein
      interactions. Dimer dissociation was further scrutinized in the presence of an
      inactive, point mutant form of the enzyme. As a result of subunit exchange
      between the native and mutant enzymes and the formation of an inactive
      heterodimer, there was a time-dependent decrease in the activity of the native
      protease. Enzyme activity could be reinstated with the addition of an active-site
      directed inhibitor (L-365862) which selectively binds active dimers. The rate of
      dimer dissociation was found to also decrease with pH. At pH 5.5 and 30 degrees
      C, the half-life for subunit dissociation is about 0.5 h. The slow dissociation,
      coupled with the high stability for dimer association, attests to the importance
      of allowing sufficient time for dimer-monomer equilibration in kinetic assays in
      order to avoid reaching erroneous conclusions in studies of dimer dissociation.

PMID- 8286368
TI  - Nitrogenase and biological nitrogen fixation.
AB  - Biological nitrogen fixation is catalyzed by the nitrogenase enzyme system which
      consists of two metalloproteins, the iron (Fe-) protein and the molybdenum-iron
      (MoFe-) protein. Together, these proteins mediate the ATP-dependent reduction of
      dinitrogen to ammonia. Recent crystallographic analyses of Fe-protein and MoFe
      protein have revealed the polypeptide fold and the structure and organization of
      the unusual metal centers in nitrogenase. These structure provide a molecular
      framework for addressing the mechanism of the nitrogenase-catalyzed reaction.
      General features of the nitrogenase system, including conformational coupling of
      nucleotide hydrolysis, aspects of the cluster structures, and the general spatial
      organization of redox centers within the protein subunits, are relevant to a wide
      range of biochemical systems.

PMID- 8286369
TI  - Probing the metal binding sites of Escherichia coli isoleucyl-tRNA synthetase.
AB  - The metal binding properties of isoleucyl-tRNA synthetase (IleRS) from
      Escherichia coli were studied by in vivo substitution of the enzyme-bound metals.
      Purified E. coli IleRS was shown to have two tightly bound zinc atoms per active
      site. Cobalt- and cadmium-substituted IleRS were also found to contain two
      tightly bound Co2+ and Cd2+ atoms per polypeptide chain, respectively. The d-d
      transitions in the low energy absorption spectrum of Co(2+)-substituted IleRS
      were characteristic of that expected for two tetrahedrally coordinated Co2+
      metals. Apo-IleRS was found to be inactive in both the aminoacylation of
      tRNA(Ile) and in the isoleucine-dependent ATP-pyrophosphate exchange reactions.
      Both Co(2+)- and Cd(2+)-substituted IleRS were found to have kcat/Km values in
      the isoleucine-dependent ATP-pyrophosphate exchange assay approximately 5-fold
      lower than the native Zn2+ enzyme. A single enzyme-bound Zn2+ or Co2+ atom per
      polypeptide chain could be removed by dialysis of Zn(2+)- or Co(2+)-substituted
      IleRS against 1,10-phenanthroline. Removal of one of the two enzyme-bound Zn2+
      atoms per polypeptide chain with 1,10-phenanthroline was found to decrease
      (kcat/Km)Ile by approximately 130-fold. The dependence of the kinetic parameters
      on the identity and number of enzyme-bound metals in the isoleucine-dependent ATP
      pyrophosphate exchange reaction suggests that at least one enzyme-bound metal is
      indirectly involved in aminoacyladenylate formation. Metal substitution or
      removal of one of the two enzyme-bound metals in IleRS was found to have little
      effect on the Km value for tRNA(Ile) or the kcat value for aminoacylation of
      tRNA(Ile).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286370
TI  - Human ferrochelatase is an iron-sulfur protein.
AB  - Recombinant human ferrochelatase has been expressed in Escherichia coli and
      purified to homogeneity. Metal analyses revealed approximately 2 mol of non-heme
      Fe per mol of the purified enzyme (M(r) = 40,000). The UV-visible absorption
      spectrum of the purified enzyme consists of a protein absorption at 278 nm
      (epsilon approximately 90,000 M-1 cm-1) and bands at 330 nm (epsilon
      approximately 24,000 M-1 cm-1), 460 nm (shoulder, epsilon approximately 11,000 M
      1 cm-1), and 550 nm (shoulder, epsilon approximately 9000 M-1 cm-1) that are
      indicative of a [2Fe-2S]2+ cluster. The spectra show an additional band at 415 nm
      that varied in intensity for different preparations and is attributed, at least
      in part, to a minor component of enzyme-associated high-spin Fe(III) heme. The
      presence of a single [2Fe-2S]2+,+ cluster as a redox active component of human
      ferrochelatase was confirmed by variable-temperature MCD and EPR studies of the
      dithionite-reduced enzyme which showed the presence of a S = 1/2 [2Fe-2S]+
      cluster in addition to residual high spin Fe(II) heme. The reduced enzyme
      exhibits a S = 1/2 EPR signal, g = 2.00, 1.94, 1.91 accounting for 0.75 +/- 0.25
      spins/molecule, that readily saturates at low microwave powers below 10 K but is
      observable without significant broadening at temperatures up to 100 K. The Fe-S
      cluster is labile and gradually disappears over period of 24 h, with concomitant
      loss of enzyme activity, when the enzyme is stored aerobically at 4 degrees
      C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286371
TI  - Unbleachable rhodopsin with an 11-cis-locked eight-membered ring retinal: the
      visual transduction process.
AB  - Visual transduction occurs through photorhodopsin, the primary photoproduct of
      rhodopsin, which relaxes to bathorhodopsin and a series of other intermediates
      until it reaches the metarhodopsin II stage, upon which the enzymatic cascade
      leading to vision is activated. Despite advances in areas related to visual
      transduction, the triggering process itself, a key problem in the chemistry of
      rhodopsin, has remained unsolved. In order to clarify the extent of involvement
      of the chromophoric excited state versus the 11-cis to trans isomerization, and
      as an extension of past studies with 11-cis-locked seven-membered ring rhodopsin
      (Rh7), 11-cis eight- and nine-membered ring retinal analogs, ret8 and ret9,
      respectively, have been synthesized. The bulkiness of the tetramethylene bridge
      in ret8 led to numerous unexpected obstacles in attempts to reconstitute a ret8
      containing rhodopsin (Rh8) embedded in lipid bilayer membranes. These obstacles
      were solved by using methylated rhodopsin which gave MeRh8 containing 11-cis-ret8
      as its chromophore. MeRh8 exhibited UV-vis and CD spectra very similar to those
      of native rhodopsin (Rh); furthermore, the quantum efficiency of photorhodopsin
      formation was comparable to that of Rh.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286372
TI  - Interaction of cationic porphyrins with DNA.
AB  - Utilizing linear dichroism (LD), circular dichroism (CD), and fluorescence energy
      transfer, the binding geometries of a series of Co(3+)-porphyrins and their free
      ligands were examined. The compounds studied were Co-meso-tetrakis(N
      methylpyridinium-4-yl)porphyrin (CoTMPyP) and its free ligand (H2-TMPyP), Co-meso
      tetrakis(N-n-butylpyridinium-4-yl)porphyrin (CoTBPyP) and its free ligand
      (H2TBPyP), and Co-meso-tetrakis(N-n-octylpyridinium-4-yl)porphyrin (CoTOPyP). The
      two non-metalloporphyrins exhibit negative LD, having angles of roughly 75
      degrees relative to the DNA helix axis. They also display negative CD and a
      significant contact energy transfer from the DNA bases. On the other hand, the
      three metalloporphyrins display orientation angles of roughly 45 degrees between
      the porphyrin plane and the helix axis of DNA. Furthermore, they exhibit positive
      CD and no contact energy transfer from DNA bases. These observations show that
      the metalloporphyrins are not intercalated whereas non-metalloporphyrins having
      four freely rotating meso-aryl groups intercalate between the base pairs of DNA.
      In the presence of KHSO5, the cobalt porphyrins cleave closed circular PM2 DNA in
      a single strand manner, i.e., a single activation event on the porphyrin leads to
      a break in one of the DNA strands. A kinetic analysis of the cleavage data
      revealed that cleavage rates are in the order CoTMPyP > CoTBPyP > CoTOPyP with
      the difference being due to different DNA affinities rather than differences in
      cleavage rate-constants. Based on these and earlier observations, the
      metalloporphyrins appear bound to a partially melted region of DNA.

PMID- 8286373
TI  - Hepatitis B virus direct repeat sequence: imino proton exchange rates and
      distance and torsion angle restraints from NMR.
AB  - Structural features of a trisdecamer duplex, [d(GGCAGAGGTGAAA).d(TTTCACCTCTGCC)],
      in solution are being investigated by proton one-dimensional (1D) and two
      dimensional (2D) NMR spectroscopy. This DNA sequence is comprised of the 11-base
      pair direct repeat sequence found in the hepatitis B viral genome with an
      additional base pair from the genome included on each end to minimize end effects
      on the 11-bp sequence of interest. The direct repeat sequence occurs twice in the
      viral genome; both are essential for initiation of DNA synthesis. The critical
      nature of this sequence suggests it may be a target to control replication of the
      virus. Elucidation of the structure of the direct repeat sequence could prove to
      be beneficial in targeting efforts. Structural determination via restrained
      molecular dynamics requires experimentally derived distance restraints. The
      ability to determine solution structures of biomolecules by NMR spectroscopy is
      limited by the quality and quantity of distance and torsion angle restraints that
      can be extracted from the NMR data. Techniques used to establish these restraints
      are constantly evolving and improving. Modifications in procedure are applied to
      the trisdecamer duplex to yield improvements in the determination of sugar
      conformations from COSY data and a substantial increase in the number of distance
      restraints typically garnered from 2D NOE intensity data. This increase in the
      number of distance restraints normally obtained from 2D NOE intensities was
      accomplished by utilizing a new version of the iterative complete relaxation
      matrix program MARDIGRAS with intensities extracted from a 2D NOE data set
      acquired in 90% H2O. The exchange rate of the imino and amino protons with the
      solvent water protons can now be included in the relaxation matrix calculations,
      thereby providing more accurate distances when utilizing the 2D NOE cross-peaks
      involving at least one exchangeable proton. In this lab, analysis of two-quantum
      filtered correlation (2QF-COSY) spectra to determine the conformational states of
      the sugar moieties typically employs the program package SPHINX/LINSHA to
      simulate the scalar coupling effects manifest in the cross-peaks. With enough
      data, we typically find that a single conformer is inadequate to describe sugar
      pucker, but a rapid two-state equilibrium is consistent with all the data. In the
      process, a large number of cross-peaks are simulated with a range of possible
      sugar conformation ratios, amplitudes, and line widths. A limitation of this
      procedure is the possibility of producing a nonunique solution. These methods
      rely on the ability to match the appearance of simulated cross-peaks with real
      data.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8286374
TI  - Dynamics of a flexible loop in dihydrofolate reductase from Escherichia coli and
      its implication for catalysis.
AB  - Apo-dihydrofolate reductase from Escherichia coli samples two distinct
      environments slowly on the NMR time scale at room temperature. Several assigned
      resonances belong to residues in, or proximal to, a loop (loop I) which is
      comprised of residues 9-24. This exchange process was altered (either removed or
      made fast on the NMR time scale) by deleting three hairpin turn forming residues
      from the loop and filling the gap with a single glycine [Li, L., Falzone, C. J.,
      Wright, P. E., & Benkovic, S. J. (1992) Biochemistry 31, 7826-7833]. An
      approximate value of 35 s-1 for the exchange rate associated with loop I in apo
      DHFR was obtained in two-dimensional nuclear Overhauser spectra by analyzing the
      time dependence of the cross-peak volume for N epsilon H of Trp-22, a residue
      which is located in this loop and which has resolved cross-peaks. Owing to the
      critical role that this loop plays in catalysis, the correspondence between this
      rate of conformational exchange and off-rates for tetrahydrofolate and the
      reduced nicotinamide cofactor from product and substrate complexes suggests that
      loop movement may be a limiting factor in substrate turnover.

PMID- 8286375
TI  - Roles of the aromatic residues conserved in the active center of Saccharomycopsis
      alpha-amylase for transglycosylation and hydrolysis activity.
AB  - The molecular structure of Saccharomycopsis fibuligera alpha-amylase was
      predicted by a homology-based modeling technique, and the amino acid residues
      composing the active site were displayed with color codes according to their
      order of conservation. We noticed two highly conserved aromatic residues located
      in the active center, tyrosine 83 (Y83) and tryptophan 84 (W84), and examined
      their roles in catalytic activity by site-directed mutagenesis. The W, leucine
      (L), and asparagine (N) mutants at Y83 and the L mutant at W84 showed remarkable
      enhancement of transglycosylation activity and complementary decreases in native
      hydrolysis activity. The phenylalanine (F) mutant at Y83 and the F and Y mutants
      at W84 only decreased hydrolysis activity. Mechanistic and kinetic studies of
      these mutants using a reducing-end-blocked substrate and a hydrolysis-specific
      substrate revealed a probable transglycosylation mechanism and critical
      contributions of the 83rd and 84th aromatic residues to efficient hydrolysis.
      Given that aromatic residues stack against the faces of sugars, we assumed that
      Y83 and, presumably, W84 play roles in the binding of oligosaccharide substrates
      through the stacking interaction and in the indirect fixation of the catalytic
      water molecule through hydrogen bonding with the hydroxyl of the bound
      substrates. Mutations to nonaromatic residues could cause slight changes in the
      binding topology of substrates to favor transglycosylation over hydrolysis.

PMID- 8286376
TI  - Adenosine 5'-diphosphate binding and the active site of nucleoside diphosphate
      kinase.
AB  - The X-ray structure of nucleoside diphosphate kinase (NDP kinase) from the slime
      mold Dictyostelium discoideum has been determined to 2.2-A resolution and refined
      to an R-factor of 0.19 with and without bound ADP-Mg2+. The nucleotide binds near
      His 122, a residue which becomes phosphorylated during the catalytic cycle. The
      mode of binding is different from that observed in other phosphokinases, and it
      involves no glycine-rich sequence. The adenine base makes only nonpolar contacts
      with the protein. It points outside, explaining the lack of specificity of NDP
      kinase toward the base. The ribose 2'- and 3'-hydroxyls and the pyrophosphate
      moiety are H-bonded to polar side chains. A Mg2+ ion bridges the alpha- to the
      beta-phosphate which approaches the imidazole group of His 122 from the N delta
      side. The geometry at the active site in the ADP-Mg2+ complex suggests a
      mechanism for catalysis whereby the gamma-phosphate of a nucleoside triphosphate
      can be transferred onto His 122 with a minimum of atomic motion.

PMID- 8286377
TI  - Common metal ion coordination in LIM domain proteins.
AB  - The LIM motif is a cysteine- and histidine-rich sequence that was first
      identified in proteins involved in control of gene expression and cell
      differentiation. In order to characterize structural features of the LIM domain,
      we have carried out biophysical studies on two polypeptides that display LIM
      domains: the cysteine-rich intestinal protein (CRIP) and a fragment of the
      cysteine-rich protein (CRP). Bacterial expression vectors were constructed for
      the intact CRIP molecule and the C-terminal half of CRP, designated LIM2, such
      that each expressed protein contained a single LIM domain. Both proteins were
      recovered as soluble, Zn(II)-containing proteins. The metal coordination
      properties of these two distinct LIM domain proteins were highly similar,
      suggesting that a common structural architecture may exist in LIM domain
      proteins. Both proteins exhibit a maximum of two tetrahedrally bound Zn(II) ions
      per molecule. Electronic spectroscopy of Co(II) complexes and 113Cd NMR of Cd(II)
      complexes of CRIP and LIM2 revealed a similar ligand field pattern with one
      tetrathiolate (S4) site and one S3N1 site for divalent metal ions. The nitrogen
      ligand was shown to arise from a histidyl imidazole by heteronuclear multiple
      quantum coherence NMR. The eight conserved residues within the LIM domains of
      CRIP and LIM2 include seven cysteines and one histidine. It is likely that these
      conserved residues generate the S4 and S3N1 Zn(II)-binding sites. Metal binding
      to the two sites within a single LIM domain is sequential, with preferential
      occupancy of the S4 site. Slow metal ion exchange occurs between sites within an
      LIM domain, and metal exchange with exogenous metal ions is observed, with
      exchange at the S3N1 site being kinetically more facile. In the absence of metal
      binding both proteins appear to be substantially unfolded. Metal binding
      stabilizes a tertiary fold containing appreciable secondary structural elements.
      The common metal ion coordination in CRIP and LIM2 suggests that the LIM motif
      may constitute a structural module with conserved features.

PMID- 8286378
TI  - Factor Va-membrane interaction is mediated by two regions located on the light
      chain of the cofactor.
AB  - Factor Va was incubated with 1-azidopyrene, a fluorescent lipophilic probe, in
      the presence of phospholipid vesicles composed of various proportions of
      phosphatidylcholine (PC) and phosphatidylserine (PS). The majority of the label
      was associated with the light chain of factor Va. The light chain was found to be
      labeled in the presence of phospholipid vesicles containing either 100% PC or
      100% PS. After cleavage by factor Xa and incubation with PC/PS vesicles composed
      of 75% PC and 25% PS, label was found both on the M(r) = 30,000 fragment, derived
      from the NH2-terminal portion of the bovine factor Va light chain (residues 1537
      1752), and on the M(r) = 46,000/48,000 carboxyl-terminal fragment of the factor
      Va light chain (residues 1753-2183). The M(r) = 46,000/48,000 fragment
      incorporated 1-azidopyrene independent of the phospholipid composition, while
      label incorporation into the M(r) = 30,000 fragment required phospholipid
      vesicles containing PC. No labeling of the M(r) = 30,000 fragment was observed
      with phospholipid vesicles composed of 100% PS. The label incorporation into the
      two portions of the molecule was found to be independent of the ionic strength in
      the presence of phospholipid vesicles containing 75% PC and 25% PS. In contrast,
      the labeling of the M(r) = 46,000/48,000 fragment with phospholipid vesicles
      composed of 100% PS was ionic strength dependent.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8286379
TI  - Expression of the 25-kilodalton iron-sulfur subunit of the energy-transducing
      NADH-ubiquinone oxidoreductase of Paracoccus denitrificans.
AB  - The energy-transducing NADH-ubiquinone (Q) oxidoreductase of Paracoccus
      denitrificans is composed of 14 dissimilar subunits and contains at least four
      iron-sulfur clusters [Yagi, T. (1993) Biochim. Biophys. Acta 1141, 1-17]. The
      complete DNA sequence of the gene cluster encoding the energy-transducing NADH-Q
      oxidoreductase of P. denitrificans has been determined. This paper reports the
      expression of the 25-kilodalton (kDa) (NQO2) subunit of the P. denitrificans
      enzyme complex in Escherichia coli and the characterization of the iron-sulfur
      cluster bound to the expressed subunit. The 25-kDa subunit was expressed in the
      cytoplasmic phase but not in the membrane fraction of E. coli cells and then
      purified using an affinity nickel chelation column. The purified subunit contains
      1.44 mol of non-heme iron and 1.33 mol of acid-labile sulfide/mol of subunit. EPR
      analysis of the reduced form of this subunit indicates that the expressed subunit
      contains a single binuclear [2Fe-2S] cluster. This cluster exhibits a spectrum of
      rhombic symmetry with g values of gx,y,z = 1.913, 1.942, and 1.996, which is very
      similar to the spectrum of the [2Fe-2S] cluster in the resolved flavoprotein II
      subfraction (subunit 24 + 9 kDa) of bovine heart complex I [Ragan, C. I.,
      Galante, Y. M., Hatefi, Y., & Ohnishi, T. (1982) Biochemistry 21, 590-594;
      Ohnishi, T., Ragan, C. I., & Hatefi, Y. (1985) J. Biol. Chem. 260, 2782-2788].
      The assignment of the binuclear iron-sulfur cluster of the 25-kDa subunit to an
      EPR-visible iron-sulfur cluster in the Paracoccus NADH-Q oxidoreductase in situ
      is discussed.

PMID- 8286380
TI  - Picosecond infrared study of the photodynamics of carbonmonoxy-cytochrome c
      oxidase.
AB  - Time-resolved infrared (TRIR) techniques have been employed to study the
      reactions of carbon monoxide with the cytochrome alpha 3-Cu(B) site of cytochrome
      c oxidase (CcO). The ligation dynamics immediately following photodissociation
      have been investigated using picosecond TRIR spectroscopy and linear dichroism.
      The rate of photoinitiated transfer of CO from cytochrome alpha 3 to CuB was
      measured directly by monitoring the development of the transient CuBCO
      absorption. In less than 1 ps, a stationary CuBCO spectrum develops, which
      together with the CO infrared linear dichroism is constant until the CO
      dissociates from CuB on a microsecond time scale. These observations indicate
      that the CO is transferred between metals and reaches its equilibrium
      conformation in less than 1 ps. This unprecedented ligand transfer rate has
      profound implications with regard to the structure and dynamics of the cytochrome
      alpha 3-CuB site, the functional architecture of the protein, and coordination
      dynamics in general.

PMID- 8286381
TI  - Calmodulin interaction with the skeletal muscle sarcoplasmic reticulum calcium
      channel protein.
AB  - Studies were initiated to define the equilibria of calmodulin binding to the
      skeletal muscle sarcoplasmic reticulum (SR) Ca(2+)-release channel protein in
      native SR vesicles. Calmodulin affinity-labeling experiments indicated that the
      major calmodulin receptor in heavy SR preparations was a protein of M(r) >
      450,000, corresponding to the Ca(2+)-release channel protein. [3H]Ryanodine
      binding assays indicated 10.6 +/- 0.9 pmol of high-affinity ryanodine binding per
      milligram of SR protein. Wheat germ calmodulin was derivatized with rhodamine-x
      maleimide. The affinity and binding capacity of the channel protein in SR
      vesicles for the derivatized calmodulin (Rh-CaM) were determined by fluorescence
      anisotropy in the presence of (1) 1 mM EGTA, (2) 0.1 mM CaCl2, and (3) 0.1 mM
      CaCl2 plus 1 mM MgCl2. In the presence of EGTA, Rh-CaM bound to the channel
      protein with a Kd of 8.6 +/- 0.8 nM and a Bmax of 229 +/- 7 pmol/mg, suggesting
      that calmodulin binds to the channel protein at [Ca2+] comparable to that in
      resting muscle. In the presence of 0.1 mM CaCl2, the binding equilibrium shifted
      to a two-site ligand-binding model; the high-affinity class of sites had a Bmax1
      of 54 +/- 7 pmol/mg and a Kd1 of 4.3 +/- 1.1 nM, while the lower affinity class
      of sites had a Bmax2 of 166 +/- 28 pmol/mg and a Kd2 of 239 +/- 102 nM. In the
      presence of both Ca2+ and Mg2+, there was a further change in the Rh-CaM/channel
      protein interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286382
TI  - Alpha-thrombin-induced nuclear sn-1,2-diacylglycerols are derived from
      phosphatidylcholine hydrolysis in cultured fibroblasts.
AB  - Diglycerides play an important role in a number of agonist-induced signal
      transduction pathways. We have recently demonstrated that alpha-thrombin induces
      a rapid increase in the level of diglyceride mass in the nucleus and a selective
      increase in nuclear PKC-alpha [Leach, K.L., Ruff, V.A., Jarpe, M.B., Fabbro, D.,
      Adams, L.D., & Raben, D.M. (1992) J. Biol. Chem. 267, 21816-21822]. In the
      present report, we examined the potential source of the induced nuclear
      diglycerides by examining the molecular species profiles of both the induced
      diglycerides and nuclear phospholipids by capillary gas chromatography. The
      molecular species profiles of the nuclear diglycerides generated resemble the
      species profiles of PC, and not PI species, at all times. In addition, while our
      previous data indicated that the molecular species of whole-cell phospholipids
      did not change in response to alpha-thrombin, nuclear PE was altered in a
      dramatic and selective manner in response to this agonist. These results
      demonstrate that PC hydrolysis is the predominant, if not exclusive, source of
      the alpha-thrombin-induced nuclear diglycerides in these fibroblasts.

PMID- 8286383
TI  - Bacteriorhodopsin can function without a covalent linkage between retinal and
      protein.
AB  - Light energy is transferred from retinal to the protein in bacteriorhodopsin
      after absorption of a photon resulting in changes of protein conformation. To
      examine whether the covalent bond, formed by the carbonyl group of retinal and
      the epsilon-amino group of lysine 216, is essential for this process, a mutant
      with lysine 216 replaced by alanine was expressed in Halobacterium salinarium L33
      (BO-, retinal+). Reconstitution of the chromoprotein with varying retinylidene-n
      alkylamines was possible in isolated membranes as well as in whole cells. When
      the protein in membranes with retinylidene Schiff bases of n-alkylamines of
      different lengths was reconstituted, the most stable chromoprotein was formed
      with retinylideneethylamine. The absorbance maximum was at 475 nm in alkaline
      solution and 620 nm in acidic solution. At neutral pH values both species
      equilibrate with a third one absorbing maximally at 568 nm. Reconstitution of
      whole cells with retinylideneethylamine led to a specific proton pump activity of
      30 mol of protons per mol of BR per minute. This value indicates a lower limit of
      transport; no light saturation could be reached in these measurements in contrast
      to wild-type BR where transport activities of 162 mol of protons per mol of BR
      per minute under identical conditions can be achieved. Action spectra from flash
      photolysis experiments revealed that only the 568-nm form led to a M-intermediate
      with a half-time of decay of 17 ms. In summary, it could be shown that the
      covalent linkage between retinal and the protein is basically not required for
      the function of bacteriorhodopsin as a light-driven proton pump.

PMID- 8286384
TI  - A bryostatin-sensitive protein kinase C required for nerve growth factor
      activity.
AB  - Nerve growth factor (NGF) stimulates rat pheochromocytoma cells (PC12) to
      differentiate into a neuronal-like cell that exhibits neurite extensions. The
      role of protein kinase C in signal transduction has been examined in PC12 cells
      treated with phorbol 12-myristate 13-acetate (PMA) and bryostatin, a macrocyclic
      lactone that activates protein kinase C at both the nuclear and the plasma
      membranes [Hocevar, B. A., & Fields, A. P. (1991) J. Biol. Chem. 266, 28-33]. In
      contrast to PMA down-regulation [Reinhold, D. S., & Neet, K. E. (1989) J. Biol.
      Chem. 264, 3538-3544], chronic (24 h) treatment with bryostatin blocked the
      formation of neurites in response to NGF or basic fibroblast-derived growth
      factor stimulation, but, like PMA, bryostatin did not block the induction of c
      fos or c-jun protooncogenes by NGF. Chronic bryostatin treatment down-regulated
      protein kinase C activity in the cytosolic, membrane, and nuclear fractions.
      Acute (60 min) bryostatin or NGF treatment activated cytosolic and nuclear
      protein kinase C activity, suggesting possible translocation to the nucleus.
      Bryostatin did not induce neurite outgrowth, either alone or in combination with
      PMA. Thus, the bryostatin-sensitive protein kinase C is distinct from PMA- or
      K252a-sensitive kinases previously described. The bryostatin-sensitive protein
      kinase C is necessary, but not sufficient, for neurite outgrowth and acts in the
      nucleus in a manner independent of c-fos and c-jun transcription.

PMID- 8286385
TI  - Details of the acyl-enzyme intermediate and the oxyanion hole in serine protease
      catalysis.
AB  - Raman, absorbance, and kinetic measurements were used to determine how the serine
      protease active site feature known as the oxyanion hole interacts with an acyl
      enzyme intermediate. The substrate, p-(dimethylamino)benzoylimidazolide (DAB-Im),
      was synthesized and used to prepare DAB-acyl-enzymes of wild-type (WT) and N155G
      subtilisin-BPN' (the N155G mutant lacks a fully functioning oxyanion hole), alpha
      chymotrypsin (CHT), and bovine trypsin (TRY). DAB-acyl-enzyme deacylation rate
      constants, k3, were found to span a 720-fold range at pH 7.8 (DAB-WT > DAB-TRY >
      DAB-N155G > DAB-CHT). DAB-N155G was found to deacylate 80-fold slower than DAB
      WT, indicating a 2.6 kcal/mol loss of transition-state binding energy due to this
      mutation. Absorbance spectra revealed strongly red-shifted absorbance lambda max
      values for all of the DAB-acyl-enzymes. The red shift was found to be 2.0 nm less
      in DAB-N155G, indicating that the oxyanion hole is partially responsible for this
      electronic perturbation of the DAB chromophore at the active site. Raman
      difference spectra of the DAB-acyl-enzymes measured at pH 5.0 and 8.6, with 18O
      labeling of the carbonyl, show that the molecular motions most perturbed by the
      active site are three associated with the scissile acyl bond. Most interesting is
      the carbonyl stretching vibration, v(C = O), whose motion extends into the
      hydrolytic reaction coordinate. Comparison of the v(C = O) of DAB-WT and DAB
      N155G reveals that the oxyanion hole does indeed form a hydrogen-bonding
      interaction with the carbonyl oxygen, the strength of which increases at pH 8.6.
      Interestingly, the DAB-TRY carbonyl forms very strong hydrogen bonds, even at pH
      5.0, but DAB-CHT does not, even at pH 8.6. The low-frequency (1661 cm-1) v(C =
      O)'s of pH 5.0 DAB-TRY and pH 8.6 DAB-WT are proposed to correspond to a
      tetrahedrally distorted carbonyl center like that observed in the crystal
      structure of guanidinobenzoyl-TRY (Mangel et al., 1990). The strength of hydrogen
      bonding between the DAB-acyl-enzyme's carbonyl and the oxyanion hole, as gauged
      by the v(C = O) frequency, was found to correlate positively with an increased
      deacylation rate. This correlation, as well as calculated acyl-enzyme carbonyl
      bond lengths, which indicate a 0.015-A lengthening due to the oxyanion hole
      interaction, was found to be in good agreement with previously published
      resonance Raman data of alpha, beta-unsaturated arylacryloyl-acyl-enzymes (Tonge
      & Carey, 1990b, 1992).

PMID- 8286386
TI  - A covalently trapped folding intermediate of subtilisin E: spontaneous
      dimerization of a prosubtilisin E Ser49Cys mutant in vivo and its autoprocessing
      in vitro.
AB  - The propeptide of subtilisin E (the N-terminal 77 amino acid extension) is
      required for the proper folding of the nascent mature protein and is also a
      potent and specific inhibitor of the active enzyme. Previous studies have
      demonstrated that the propeptide can renature denatured mature sequence either in
      cis or in trans and can be considered an intramolecular chaperone, since it is
      not required for activity of the mature enzyme. In this paper it is shown that a
      prosubtilisin-S49C mutant can be expressed in Escherichia coli either as a
      monomer or as a disulfide-linked dimer, (prosubtilisin-S49C)2, depending on the
      vector selected. Interconversion between (prosubtilisin-S49C)2 and prosubtilisin
      S49C could be readily achieved by reduction and oxidation in denaturing
      solutions, such as guanidine hydrochloride or urea. While the monomer can undergo
      autoprocessing in vitro under refolding conditions, the dimer is trapped in an
      intermediate state which could not be processed into active enzyme. Remarkably,
      the autoprocessing of this trapped intermediate could be induced readily upon
      reduction by dithiothreitol. This disulfide-linked (prosubtilisin-S49C)2 is
      fairly stable, but does tend to aggregate when the ionic strength of the solution
      is reduced below 0.1 M. The disulfide-linked (prosubtilisin-S49C)2 has far- and
      near-UV CD spectra revealing the presence of both secondary and tertiary
      structures, respectively, similar to those of the active mature monomer. Hence
      this autoprocessing-competent state appears to be a "late" folding intermediate,
      arising after the "molten globule" state formed in the absence of the
      prosequence, that has no discernible tertiary structure.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8286387
TI  - Specific interaction between H1 histone and high mobility protein HMG1.
AB  - High mobility group proteins HMG1 and -2 and histone H1 are structural components
      of chromatin. Previously, we reported that HMG1 interacts with H1 histone in a
      way that modulates the ability of H1 to condense DNA in vitro, suggesting that
      these proteins may act together in vivo to regulate locally the condensation
      state of chromatin, possibly affecting replication and/or transcription. Here we
      show that reduced (native) HMG1 binds to H1 cooperatively at pH 6.0 as a tetramer
      with a dissociation constant of 3.4 x 10(-8) M, and at pH 7.5 as a monomer with a
      dissociation constant less than 10(-9) M. Denaturation through oxidation of
      sulfhydryl groups has a strong effect on the interaction of HMG1 with H1 histone,
      suggesting that the reduced state of HMG1 is critical to its function. Oxidized
      HMG1 failed to bind H1 at pH 7.5, and its binding at pH 6 was biphasic; the first
      three (or two) molecules of H1 were bound with a dissociation constant of 2 x 10(
      8) M with negative cooperativity, and the last one (or two) H1's were bound
      cooperatively with KD = 1.8 x 10(-7) M. Regulation of the pH or the concentration
      of some other ion may be used in vivo to alter the interactions between HMG1 and 
      2, H1 histone, and DNA.

PMID- 8286388
TI  - DNA recognition by the NIT2 nitrogen regulatory protein: importance of the
      number, spacing, and orientation of GATA core elements and their flanking
      sequences upon NIT2 binding.
AB  - NIT2, a global positive-acting regulatory protein in Neurospora crassa, activates
      the expression of a series of unlinked structural genes in the nitrogen
      regulation circuit. NIT2 binding sites in the promoter region of the nit-3, alc,
      and lao genes are very different in sequence context except for the presence of
      at least two copies of a GATA core sequence. Changing a single nucleotide of only
      one of two closely spaced GATA core elements abolished NIT2 binding,
      demonstrating their importance for NIT2 binding. The effect of altering the
      number, orientation, or spacing of paired GATA elements and the importance of 5'-
      and 3'-flanking sequences upon NIT2 binding were examined. Strong binding sites
      for a NIT2-beta GAL fusion protein appear to contain at least two GATA elements,
      which can have varied spacing but must be within a certain effective distance,
      approximately 30 bp, of each other. Surprisingly, the orientation of GATA
      elements and their flanking sequences have only modest effects upon NIT2 binding.

PMID- 8286389
TI  - Chemical probing studies of variants of the genomic hepatitis delta virus
      ribozyme by primer extension analysis.
AB  - We have investigated in detail the higher order structure of the genomic
      hepatitis delta virus (HDV) ribozyme using various base-specific chemical probes
      under native, semi-denaturing, and denaturing conditions. The bases of the HDV
      ribozyme were probed by treatment with dimethyl sulfate [which reacts with A (at
      N1) and C (at N3)] and a carbodiimide [which reacts with U (at N3) and G (at
      N1)]. In addition, for probing G residues (at N7), RNA samples were treated with
      NaBH4 and aniline after modification by treatment with dimethyl sulfate. The
      sites of modified positions were identified by primer extension analysis with
      reverse transcriptase. In general, our results are consistent with the proposed
      pseudoknot model of secondary structure, a model that is based on data from
      ribonucleolytic cleavage experiments. Our results provide clues to the
      identification of interacting bases in the HDV ribozyme. Furthermore, using this
      method we identified local conformational changes in several stem variants.

PMID- 8286390
TI  - Microfibril-associated glycoprotein: characterization of the bovine gene and of
      the recombinantly expressed protein.
AB  - Microfibrils having a diameter of 10-12 nm, found either in association with
      elastin or independently, are an important component of the extracellular matrix
      of many tissues. Because isolation of native proteins composing the microfibrils
      has proven difficult, information on structure/function relationships is limited.
      In order to extend our understanding of the 31-kDa microfibril-associated
      glycoprotein (MAGP), the bovine gene has been cloned and characterized and the
      protein has been expressed in a eukaryotic system. The compact coding portion of
      the gene is contained in 4.5 kbp of genomic DNA and does not appear to share any
      domain motifs with other known proteins. The size, amino acid composition, and
      sequence of the amino terminus of the secreted recombinant protein (rMAGP) all
      agree with values predicted by the nucleotide sequence of the cDNA used in the
      expression vector. The rMAGP reacts with a monospecific antibody prepared against
      a defined amino acid sequence of the natural molecule and reacts specifically
      with recombinantly produced tropoelastin, suggesting that rMAGP will be a useful
      reagent with which to study its interaction with other extracellular matrix
      components.

PMID- 8286391
TI  - Reconstitution of the biosynthetic pathway of selenocysteine tRNAs in Xenopus
      oocytes.
AB  - Selenocysteine is cotranslationally introduced into a growing polypeptide in
      response to certain UGA codons in selenoprotein mRNAs. The biosynthesis of this
      amino acid initiates by aminoacylation of specific tRNAs (designated
      tRNA([Ser]Sec)) with serine and subsequent conversion of the serine moiety to
      selenocysteine. The resulting selenocysteyl-tRNA then donates selenocysteine to
      protein. In most higher vertebrate cells and tissues examined, multiple
      selenocysteine isoacceptors have been described. Two of these have been
      determined to differ by only a single modified residue in the wobble position of
      the anticodon. In addition, the steady-state levels and relative distributions of
      these isoacceptors have been shown to be influenced by the presence of selenium.
      In order to gain a better understanding of the relationship between these tRNAs
      and how they are regulated, both the Xenopus selenocysteine tRNA gene and an in
      vitro synthesized RNA have each been injected into Xenopus oocytes and their
      maturation analyzed. In this system, selenium enhanced RNA stability and altered
      the distribution of isoacceptors that differ by a single ribose methylation.
      Interestingly, the biosynthesis of one of these modified nucleosides (5
      methylcarboxymethyl-2'-O-methyluridine), which has been identified only in the
      wobble position of selenocysteine tRNA, also occurs in oocytes. Examination of
      the modified residues in both the naturally occurring Xenopus selenocysteine tRNA
      and the products generated from exogenous templates in oocytes demonstrated the
      faithful reconstruction of the biosynthetic pathway for these tRNAs.

PMID- 8286392
TI  - Detailed study of sequence-specific DNA cleavage of triplex-forming
      oligonucleotides linked to 1,10-phenanthroline.
AB  - We introduced eight bases, including four base analogs, into 15-mer triplex
      forming oligonucleotides (TFOs) [d-psTTTCTTTNTTTTCTT; ps = thiophosphate; N = A,
      G, C, T, 2'-deoxyinosine (I), 2'-deoxyxanthosine (X), 5-methyl-2'-deoxycytidine
      (m5C), or 5-bromo-2'-deoxyuridine(br5U)] to investigate the Hoogsteen-like
      hydrogen bonding to the base in the target 34-mer strand (d
      TGAGTGAGTAAAGAAARAAAAGAATGAGTGCCAA.d-TTGGCACTCATTCTTTTYTTTCT TTACTCACTCA; RY =
      AT, GC, TA, or CG). We examined the thermal stability of 15-mer triplexes in
      buffer containing 100 mM sodium acetate and 1 M NaCl at pH 5.0. The triplexes
      with typical triplets of T.AT (51.3 degrees C), br5U.AT (52.4 degrees C), C+.GC
      (66.7 degrees C), and m5C+.GC (66.8 degrees C) at the central position showed
      relatively higher Tm values, as expected. The relatively high stability of the
      X.AT triplex (39.8 degrees C) was observed. Among the N.TA triplets, G.TA (44.8
      degrees C) was thermally the most stable, and moreover, the data showed that the
      N.TA triplet was also stabilized by I in the N position (40.7 degrees C).
      Furthermore, the TFOs were converted to DNA-cleaving molecules by introducing a
      newly synthesized 1,10-phenanthroline (OP) derivative on the thiophosphate group
      at the 5' end. Cleavage reactions of the 32P-labeled DNA (34-mer) were carried
      out. The cleavage efficiencies were compared to the Tm values of triplexes with
      or without an OP derivative. Results showed that the increased cleavage yields
      reflect the higher thermal stability of the triplex formed in most cases, but a
      few exceptional cases existed. Especially, the G-containing TFO did not show the
      above correlation between thermal stability and cleavage yield.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8286393
TI  - Hydroxyl radical footprinting of calicheamicin. Relationship of DNA binding to
      cleavage.
AB  - The binding to DNA by calicheamicin epsilon (CLM epsilon), the rearranged and
      reduced product of the diynene antitumor antibiotic calicheamicin gamma 1I (CLM
      gamma 1I), was studied using the method of hydroxyl radical footprinting. The
      drug binding sites determined in this way were compared to locations of double
      stranded DNA cleavage by thiol-activated CLM gamma 1I. The results of these
      experiments show that CLM epsilon lies in the minor groove in an extended
      conformation protecting approximately four nucleotides on each strand of DNA.
      Sites of CLM epsilon binding correlate to sites of CLM gamma 1I cleavage with
      protection by CLM epsilon occurring mainly to the 3' side of the site of C5'
      hydrogen abstraction. From these results, it is possible to propose global
      structures of the drug/DNA complexes such that the oligosaccharide side chain is
      arrayed to the 3' side of the site of C5' hydrogen abstraction. This conclusion
      is entirely consistent with the results of recent atom-transfer experiments
      [Hangeland, J.J., De Voss, J.J., Heath, J.A., Townsend, C.A., Ding, W.-D.,
      Ashcroft, J., & Ellestad, G.A. (1992) J. Am. Chem. Soc. 114, 9200-9202]. Somewhat
      greater protection on the strand undergoing C5' hydrogen abstraction was observed
      to the 5' side of the site of attack owing presumably to proximity of the methyl
      carbamate portion of the drug with DNA. Overall, binding is seen where cleavage
      is seen in accord with thermodynamics of drug association to DNA being important
      in determining the sites of cleavage.

PMID- 8286394
TI  - Molecular cloning and primary structure of rat testes metalloendopeptidase EC
      3.4.24.15.

PMID- 8286395
TI  - Bioenergetic aspects of the translocation of macromolecules across bacterial
      membranes.
AB  - Bacteria are extremely versatile in the sense that they have gained the ability
      to transport all three major classes of biopolymers through their cell envelope:
      proteins, nucleic acids, and polysaccharides. These macromolecules are
      translocated across membranes in a large number of cellular processes by specific
      translocation systems. Members of the ABC (ATP binding cassette) superfamily of
      transport ATPases are involved in the translocation of all three classes of
      macromolecules, in addition to unique transport ATPases. An intriguing aspect of
      these transport processes is that the barrier function of the membrane is
      preserved despite the fact the dimensions of the translocated molecules by far
      surpasses the thickness of the membrane. This raises questions like: How are
      these polar compounds translocated across the hydrophobic interior of the
      membrane, through a proteinaceous pore or through the lipid phase; what drives
      these macromolecules across the membrane; which energy sources are used and how
      is unidirectionality achieved? It is generally believed that macromolecules are
      translocated in a more or less extended, most likely linear form. A recurring
      theme in the bioenergetics of these translocation reactions in bacteria is the
      joint involvement of free energy input in the form of ATP hydrolysis and via
      proton sym- or antiport, driven by a proton gradient. Important similarities in
      the bioenergetic mechanisms of the translocation of these biopolymers therefore
      may exist.

PMID- 8286396
TI  - A dialogue on Ca2+ oscillations: an attempt to understand the essentials of
      mechanisms leading to hormone-induced intracellular Ca2+ oscillations in various
      kinds of cell on a theoretical level.

PMID- 8286397
TI  - The proton activity at cryogenic temperatures--a possible influence on the spin
      state of the heme iron of cytochrome P-450cam in supercooled buffered solutions.
AB  - The electronic absorption spectra for camphor-bound cytochrome P-450cam have been
      analysed in the temperature range between 78 K and 298 K. The well-known high
      spin/low-spin equilibrium has been detected between 298 K and 220 K. Depending on
      the cooling rate, below 220 K a new species was found in the absorption spectra.
      In contrast, the electronic absorption spectra for camphor-free cytochrome P
      450cam between 78 K and 295 K show no significant spectral changes. The
      conversion between the spin states of camphor-bound cytochrome P-450cam and the
      appearance of the new species do not correspond to the temperature-induced change
      in the paH value of the aqueous glycerol mixture containing phosphate or
      cacodylate buffer (paH 7.0). For this study a spectroscopic procedure for the
      determination of the temperature dependence of the paH value of the solvent for
      the range 78-295 K is presented using dyes as pH-indicators. It is shown that the
      state of the acid-base equilibrium frozen in is strongly dependent on the cooling
      rate of the mixture.

PMID- 8286398
TI  - Effects of deletions in the uncA-uncG intergenic regions on expression of uncG,
      the gene for the gamma subunit of the Escherichia coli F1Fo-ATPase.
AB  - The gamma subunit of the E. coli F1Fo-ATPase is coded for by uncG. This gene is
      poorly expressed compared to uncA (alpha subunit), which precedes uncG in the unc
      operon. The genes are separated by a 50-nucleotide intergenic region. We examined
      the effects of a set of deletions in this region on the relative expression of
      uncA'-'lacZ and uncG'-'lacZ translational fusion genes located either in the
      chromosomal unc operon or at the chromosomal lambda att site. The gene for the
      alpha subunit was expressed 3-6-times better than the gene for the gamma subunit,
      depending upon chromosomal location. Deletion analysis revealed that the uncA
      uncG intergenic region significantly affects expression of uncG, but the Shine
      Dalgarno region is not absolutely required for expression of uncG. Different
      deletions resulted in either increased or decreased expression of uncG.

PMID- 8286399
TI  - Structure of the binuclear heme iron-copper site in the quinol-oxidizing
      cytochrome aa3 from Bacillus subtilis.
AB  - Cytochrome aa3-600 is a terminal quinol oxidase of Bacillus subtilis, belonging
      to the large family of structurally and functionally related respiratory enzymes
      to which the mitochondrial cytochrome c oxidase also belongs. However, the CuA
      center typical of the cytochrome c oxidases is lacking from cytochrome aa3-600.
      The presence of only one copper, viz. CuB of the binuclear heme iron-copper site,
      makes cytochrome aa3-600 especially suitable for XAS analysis of this structure.
      Cu and Fe XAS data for fully oxidized cytochrome aa3-600 indicate a structure for
      the binuclear site similar to that previously reported for mitochondrial
      cytochrome c oxidase (see Powers et al. (1981) Biophys. J. 34, 465-468). Heme
      Fea3 has a proximal histidine nitrogen ligand 2.10 +/- 0.02 A from the iron, and
      a distal S or Cl ligand at 2.36 +/- 0.03 A. The latter is also a ligand of CuB
      (2.21 +/- 0.02 A), and apparently forms a bridge between the two metals which are
      3.70 +/- 0.06 A apart. CuB has two more close-lying ligands at 1.95 +/- 0.02 A,
      which are likely histidine nitrogens. The similarity between EXAFS of CuB and
      type 1 'blue' copper is contrasted to EPR and optical spectroscopic properties of
      CuB, and the nature of the bridging ligand is discussed.

PMID- 8286400
TI  - An NADH-diaphorase is located at the cell plasma membrane in a mouse
      neuroblastoma cell line NB41A3.
AB  - Plasma membranes from most mammalian cells display significant transplasma
      membrane oxidoreductase (PMO) activity. The enzymes use an extracellular,
      impermeant electron acceptor as substrate and intracellular reduced pyridine
      nucleotide as electron donor. The plasma membrane from a neuroblastoma cell line,
      NB41A3, has been biotinylated and purified by immunoprecipitation with avidin and
      antiavidin-antibodies. The protein recovery of an immunopurified membrane
      preparation was < 0.15% of the protein content in the cell extract. The
      preparation displays an increase in the specific activity of PMO's of 15- to 20
      fold compared to the activity in whole cells. With this approach the presence of
      a NADH-diaphorase within the cell plasma membrane can be demonstrated. This
      activity accounts for about one third of the total cellular diaphorase activity.
      The PMO activity cannot be attributed to an increased permeabilization of the
      plasma membrane induced upon biotinylation nor to intracellular activity from
      lysed cells. Activation of basal metabolism (glycolysis) stimulates PMO activity
      up to approx. 54%, presumably through a raise of the intracellular NADH store.
      PMO also promotes cell growth at low substrate concentrations (0.1-1 microM).
      Native gel electrophoresis of iminobiotinylated and affinity purified plasma
      membrane extracts displays two diaphorase-positive bands, indicating that a
      homogeneous cell population may express several PMO activities at the plasma
      membrane.

PMID- 8286401
TI  - Flash photolysis of the carbon monoxide compounds of wild-type and mutant
      variants of cytochrome bo from Escherichia coli.
AB  - The carbon monoxide compounds of the fully reduced and mixed valence forms of
      cytochrome bo from Escherichia coli were laser photolysed under anaerobic
      conditions at room temperature. The carbon monoxide recombined with
      characteristic rate constants of 50 s-1 or 35 s-1 in the fully reduced and mixed
      valence forms, respectively. Rates of CO recombination with the fully reduced
      enzyme were examined in a variety of mutant forms of cytochrome bo, produced by
      site-directed mutagenesis. A method was developed to deconvolute cytochromes bo
      and bd, leading to some reassessment of histidine ligands to the metals.
      Significant changes in the rate constant of recombination of carbon monoxide
      occurred in many of these mutants and these results could be rationalised
      generally in terms of our current working model of the folding structure of
      subunit I. In the mixed valence form of the enzyme the transient photolysis
      spectra in the visible region are consistent with a rapid electron redistribution
      from the binuclear centre to the low-spin haem. This electron transfer is
      biphasic, with rate constants of around 10(5) and 8000 s-1. The process was also
      examined in the His-333-Leu mutant, in which a putative histidine ligand to CuB
      is replaced by leucine, and which results in the loss of the CuB. It appeared
      that rapid haem-haem electron transfer could still occur. The observation that
      CuB is apparently not required for rapid haem-haem electron transfer is
      consistent with the recently proposed model in which the two haems are positioned
      on opposite sides of transmembrane helix X in subunit I of the oxidase.

PMID- 8286402
TI  - Molecular cloning of hydrogenosomal ferredoxin cDNA from the anaerobic
      amoeboflagellate Psalteriomonas lanterna.
AB  - Anaerobic parasitic and free living protozoa and anaerobic rumen fungi often
      contain a characteristic organelle, the hydrogenosome. Recently obtained
      molecular data show that hydrogenosomes in parasitic protozoa probably use a
      mitochondria-like protein targeting mechanism, whereas for hydrogenosomes in
      fungi a microbody-like mechanism is inferred. Here we present, to our knowledge,
      the first sequence data of a hydrogenosomal protein in a free-living anaerobic
      protozoan. It is shown that ferredoxin of the amoeboflagellate Psalteriomonas
      lanterna is similar to hydrogenosomal ferredoxin of the parasite Trichomonas
      vaginalis. We suggest that the two ferredoxins use similar organelle targeting
      mechanisms.

PMID- 8286403
TI  - Molecular cloning, sequencing and expression of cDNA encoding human
      coproporphyrinogen oxidase.
AB  - A complete cDNA clone encoding human coproporphyrinogen (coprogen) oxidase, the
      sixth enzyme in the heme biosynthetic pathway, has been isolated from a human
      placenta cDNA library. The cDNA had an open reading frame of 1062 base pairs
      encoding a protein of 354 amino acid residues (M(r) 40,291). Amino acid
      sequencing showed that the mature enzyme consists of 323 amino acid residues
      (M(r) 36,842) with a putative leader peptide of 31 amino acid residues. The human
      enzyme showed an 86% identity to the mouse enzyme. In addition, the recombinant
      enzyme which did not contain leader peptide was actively expressed in Escherichia
      coli. The isolation and expression of cDNA for human coprogen oxidase should
      facilitate studies of the structure of the gene as well as characterization of
      molecular lesions causing hereditary coproporphyria.

PMID- 8286404
TI  - Molecular cloning and nucleotide sequencing of Schizosaccharomyces pombe
      homologue of the class II fructose-1,6-bisphosphate aldolase gene.
AB  - DNA fragment containing Schizosaccharomyces pombe homologue of the class II
      fructose-1,6-bisphosphate aldolase gene was cloned and sequenced. A long open
      reading frame, which encodes a polypeptide of 358 amino acid residues, was found
      in the sequence. Amino acid sequence deduced from the nucleotide sequence is 63%
      homologous to the amino acid sequence of the enzyme of Saccharomyces cerevisiae.
      Northern blot analysis revealed that 1.3 kb poly(A)+ RNA is transcribed from this
      DNA sequence.

PMID- 8286405
TI  - Nucleotide sequence of a rice root ferredoxin-NADP+ reductase cDNA and its
      induction by nitrate.
AB  - A ferredoxin-NADP+ reductase (FNR) cDNA was isolated from a lambda gt 11 cDNA
      library constructed from the roots of nitrate-induced rice (Oryza sativa L. cv.
      Kinmaze) seedlings. The nucleotide sequence of this clone contains a 1134
      nucleotide open reading frame. The N-terminal 62 amino acid stretch was assigned
      to the transit sequence, followed by 316 residues for the mature protein. The
      rice root FNR shows only 49% sequence identity to that of the leaf enzyme, but
      the regions of the binding sites to ferredoxin, NADP-PPi and NADP+ are highly
      conserved between the two enzymes. The root FNR mRNA was induced transiently by
      the addition of nitrate, but not by ammonia. The results support the view that
      the root FNR is involved in the nitrate assimilation in nonchlorophyllous
      tissues.

PMID- 8286406
TI  - Cloning and sequencing of the gene encoding spinach ferredoxin-dependent
      glutamate synthase.
AB  - The nucleotide sequences of two cDNA clones, totalling 4948 bp in length,
      encoding 98% of the 1483 amino acids of the mature form of the ferredoxin
      dependent glutamate synthase of spinach chloroplasts have been determined. The
      amino-terminal sequence of the enzyme has been determined by direct sequencing of
      the protein. The deduced amino-acid sequence of the spinach enzyme is 83%
      identical to that of the ferredoxin-dependent maize enzyme and shows significant
      sequence homology to two prokaryotic NAD(P)H-dependent glutamate synthases.
      Analysis of spinach genomic DNA indicates the presence of a single-copy gene for
      the spinach enzyme. Northern analysis reveals the presence of a single 5.5 kb
      transcript, which is present in higher levels in young spinach leaves than in
      older leaves.

PMID- 8286407
TI  - The chloroplast CF0I subunit can replace the b-subunit of the F0F1-ATPase in a
      mutant strain of Escherichia coli K12.

PMID- 8286408
TI  - A new member to the astacin family of metalloendopeptidases: a novel 1,25
      dihydroxyvitamin D-3-stimulated mRNA from chorioallantoic membrane of quail.
AB  - 1,25-Dihydroxyvitamin D-3 is essential for the utilization of eggshell calcium by
      avian embryo through the chorioallantoic membrane (CAM). A cDNA library was
      constructed from poly(A)+ RNA extracted from vitamin D-deficient CAMs given 1,25
      dihydroxyvitamin D-3. Screening this library by differential hybridization
      yielded a full-length (approximately 1.8 kb) cDNA, whose corresponding mRNA is
      increased 3-fold 2.5 h after a single injection of 1,25-(OH)2D3. The complete
      nucleotide sequence for the full-length cDNA has been determined. An open-reading
      frame, corresponding to a 310 amino acid, 41 kDa protein was found. Searching
      protein sequence data bases revealed a strong similarity to the following
      proteases: astacin, a crayfish digestive protease, Oryzias latipes hatching
      enzyme constituent protease (Orz), Xenopus laevis developmentally regulated UVS.2
      protein secreted by the hatching gland of embryos, the NH2-terminal domain of
      human bone morphogenetic protein (BMP-1) and Drosophila dorsal-ventral patterning
      tolloid. The cDNA has approximately 36% overall identity with astacin and BMP-1,
      and is more than 60% identical to either Orz or UVS.2. Moreover, multiple
      alignment analysis indicates that 37 residues, including 3 cysteine residues, are
      strictly conserved in the complete 200-amino acid astacin sequence. All 6
      proteins contain a zinc-binding motif (HEXXH), found at the active site of most
      metalloendopeptidases. This motif is found within an extended sequence of
      HEXXHXXGFXHE that is unique to this subgroup of metalloendopeptidases. In
      addition, the 6 proteins have 50% identity (including the present cDNA) and 79%
      are conserved in 4 of these proteins in a 24-amino acid sequence that includes
      the putative active site. The level of mRNA for the new protein reaches a maximum
      at day 12 of embryonic life and declines thereafter. It is suggested that this
      clone corresponds to an mRNA encoding for a protease that may play a role in the
      degradation of eggshell matrix.

PMID- 8286409
TI  - Cloning and sequence analysis of the beta subunit of the human translocon
      associated protein.
AB  - A cDNA corresponding to the beta subunit of the human translocon-associated
      protein was cloned and sequenced. The polypeptide is 183 amino acids long and 96%
      homologous to its canine counterpart. Both polypeptides contain a cleavable
      signal sequence, an NH2-terminal domain extruding in the endoplasmic reticulum
      lumen, a transmembrane domain and a COOH-terminal domain located in the
      cytoplasm.

PMID- 8286410
TI  - Rat desmin gene structure and expression.
AB  - The isolation of two partial genomic clones and a near full length cDNA clone
      encoding the rat intermediate filament protein desmin is reported. Desmin is a
      differentiation marker for all types of muscle cells. The nucleotide order of the
      coding region and 0.1 kb of 5'-flanking sequences of the rat desmin gene has been
      determined. One genomic clone encompasses exons I-III and approx. 12 kb of 5'
      flanking sequences, while the other clone contains exons VII-IX and about 12 kb
      of 3'-flanking sequences. Northern analysis of RNA from different organs reveals
      that, as expected, desmin is expressed in striated, heart and smooth muscle cells
      containing tissues; among other tissues, lung displays relatively high expression
      levels, while desmin mRNA is barely detectable in spleen, kidney and liver. S1
      mapping reveals that the same transcription initiation site is used in all desmin
      mRNA containing tissues.

PMID- 8286411
TI  - Synthesis and expression of a gene coding for Erythrina trypsin inhibitor (ETI).
AB  - A gene coding for Erythrina trypsin inhibitor (ETI) was designed, based on the
      published N-terminal sequence of the protein, and synthesized by an
      oligonucleotide-directed single strand break-repair mechanism. Direct expression
      from the expression vector pBtac1 was unsuccessful. A construct, encoding an
      extended methionyl N-terminal amino acid was expressed from the vector pET12a
      which supplies a signal sequence for export to the periplasm. Most of the
      expressed protein was located in the cytoplasm but because the periplasm is an
      environment conducive to the formation of disulphide bridges, only periplasmic
      protein was extracted. Cyanogen bromide cleavage at the sole methionyl residue
      removed the undesired amino acid residues that remained after signal sequence
      peptidase processing. The resultant ETI was assayed against trypsin and tissue
      plasminogen activator and found to have activity similar to that of natural ETI.

PMID- 8286412
TI  - Site-directed mutagenesis of the synthetic Erythrina trypsin/tissue plasminogen
      activator (tPA) inhibitor encoding-gene to compare the interaction of Erythrina
      and soybean trypsin inhibitor with tPA.
AB  - Erythrina trypsin inhibitor (ETI) has good structural and sequence homology with
      soybean trypsin inhibitor (STI). However, STI does not inhibit tPA. From the
      three-dimensional structure of ETI it was known that the N-terminus of the
      molecule forms a finger-like structure stabilized by hydrogen bonds and
      hydrophobic interactions. In addition, the N-terminal finger region is located in
      close proximity to the reactive site loop and the N-terminal residue (Val) is
      bound up in the finger region. In STI the N-terminal region is located in close
      proximity to the reactive site loop and is folded into a structure similar to
      that in ETI. It was hypothesized that the N-terminal region is stabilized as in
      ETI and that the N-terminal residue of STI (Asp), because of its hydrophilic
      nature, is not involved in the structured N-terminal finger region of this
      protein. This leaves Asp1 of STI free to form an ion pair with Lys60 of trypsin,
      when STI and trypsin interact. When amino acid sequences of trypsin and the C
      terminus of tPA are aligned for optimum homology, it is seen that there are a
      number of insertion sequences in tPA that are thought to be accommodated in the
      form of protrusions. One of these can be seen to occur in the region that lies
      opposite the Lys60 region of trypsin. It is suggested in this work that the N
      terminal Asp of STI and this protrusion of tPA sterically prevent the two
      proteins from approaching close enough for binding and inhibition to occur. A
      modified form of ETI was produced with an Asp residue N-terminal to Val to
      simulate the N-terminal region of STI. The active sites were titrated against
      trypsin and assayed against tPA. The results showed that the modified form of ETI
      had activity towards tPA similar to that of STI. This evidence indicates strongly
      that the N-terminal Asp of STI prevents its binding to and inhibiting tPA.

PMID- 8286413
TI  - In vitro conversion of recombinant human proapolipoprotein A-I to apolipoprotein
      A-I.
AB  - We recently investigated the in vivo conversion of recombinant human
      proapolipoprotein A-I (rh-Met-proapo A-I) from E. coli to apolipoprotein (apo) A
      I in rabbits. In vitro incubation of rh-Met-proapo A-I with rabbit serum produced
      mature apo A-I3 isoproteins, as determined by the immunoblotting method. However,
      at the time we were unable to chemically confirm a newly produced protein band
      which appeared at the position of human apo A-I3. Since then, we have confirmed
      the amino acid sequence of the protein using a membrane protein sequence
      technique, and have concluded that it corresponds to human apo A-I3.

PMID- 8286414
TI  - Purification and identification of two major single-stranded binding proteins of
      yeast Saccharomyces cerevisiae as ribosomal protein L4 and histone H2B.
AB  - Affinity chromatography on single-stranded DNA cellulose (ssDC) is useful for
      purification of single-stranded RNA and single-stranded DNA binding proteins.
      Most of the proteins purified off of this resin have proven to be
      ribonucleoproteins, with various roles in RNA processing. A homogenate of the
      yeast Saccharomyces cerevisiae shows perhaps a dozen major protein species, and
      many more minor protein species, upon elution from ssDC. A major protein species
      of 30-31 kDa that elutes from ssDC between 0.35 and 0.45 M NaCl was purified to
      homogeneity. V8 protease was used to fragment this protein, and the peptides so
      generated were purified by HPLC and sequenced. From the sequence so derived six
      synthetic oligonucleotides were made. These oligonucleotides were used to pull
      out the corresponding gene from a yeast genomic library. The entire gene was
      eventually found on a 4.4 kb BamHI fragment. This entire fragment was sequenced.
      The sequence showed three open reading frames (ORFs). ORF1 was the p30 gene, for
      all six V8 peptide fragment sequences were found in it. Published here is the
      sequence for ORF1. Sequence comparisons of this sequence to the protein sequence
      databases showed that it is ribosomal protein L4. Another major ssb of yeast,
      which migrates as a doublet of 15-16 kDa, was also purified. N-terminal peptide
      sequencing of this protein produced a sequence identical to that for histone H2B.

PMID- 8286415
TI  - Cloning of cDNA for rat pro alpha 1(III) collagen mRNA. Different expression
      patterns of type I and type III collagen and fibronectin genes in experimental
      granulation tissue.
AB  - A cDNA clone for rat pro alpha 1(III) collagen mRNA was isolated from a cDNA
      library constructed for poly(A)+ RNA from 15-day experimental granulation tissue.
      Two clones, pRGR1 and pRGR5, were characterized by restriction mapping and
      sequencing. Comparison with human type III collagen sequences revealed 92%
      identity at the level of translated amino acids, and 88% identity at nucleotide
      level in the coding region. In the 3'-untranslated sequence the identity was even
      higher (90%). The clones were used together with cDNA clones for type I collagen
      chains, fibronectin and gamma-actin to study the expression of the corresponding
      mRNAs during the development of experimental sponge-induced granulation tissue in
      rats. These studies revealed a marked activation of type I and type III collagen
      genes during the second week of granuloma development followed by a transient
      reduction in their levels during the third week. The mRNA levels for both
      collagen types remained relatively unchanged from day 25. The molar ratio of pro
      alpha 1(III) and pro alpha 1(I) collagen mRNAs was at a maximum on day 6, and
      then decreased to reach a plateau by the end of the third week. Fibronectin mRNA
      levels were found to increase slower; the maximum value was reached during the
      fifth week of granuloma development. The mRNA levels of gamma-actin increased
      continuously up to the end of the fourth week, thus following the cellular
      maturation of the tissue.

PMID- 8286416
TI  - Effects of double amino-acid substitution polymorphism in acid beta-galactosidase
      gene in two inbred strains of mice.
AB  - We observed earlier that there are 5 nucleotide polymorphisms in the protein
      coding sequence of the acid beta-galactosidase gene between the C57BL/6J and
      DBA/2J strains of mice. Two of them result in amino acid substitutions.
      Consequences of the difference in the primary amino acid sequence were studied by
      introducing the two DBA polymorphisms into the C57BL cDNA, individually and in
      combination, by oligonucleotide-directed mutagenesis and expressing the resultant
      cDNAs in the COS-1 cell expression system. Introduction of one polymorphism,
      Asn517-->Asp into the C57BL cDNA, did not alter the acid beta-galactosidase
      activity in the transfected COS-1 cells, while introduction of Gly539-->Arg
      completely abolished the catalytic activity. When both polymorphisms were
      introduced together, as in the DBA mice, however, the acid beta-galactosidase
      activity was restored to that of the C57BL level. Thus, Asn517-->Asp appears to
      counteract the activity-abolishing effect of Gly539-->Arg, although it does not
      by itself raise the catalytic activity. All four types of cDNA generated
      similarly large amounts of stable mRNA in COS-1 cells. These results do not
      explain the significantly low acid beta-galactosidase activity in tissues of DBA
      mice, described earlier and also confirmed in this study.

PMID- 8286417
TI  - Proximal regulatory elements and nuclear activities required for transcription of
      the human Na+/H+ exchanger (NHE-1) gene.
AB  - We herein demonstrate competence of the 5' upstream region -1374 to +16 of the
      human growth factor-activatable Na+/H+ exchanger (NHE-1) gene to promote
      transcription of the chloramphenicol acetyltransferase gene in cells of hepatic
      origin (HepG2), vascular-smooth-muscle origin (VSM A7r5) and fibroblasts (3T3).
      We also describe the mapping of the regulatory elements required for such
      transcription. Sequential 5' end-deletions indicated that the 5' boundary of the
      positive regulatory elements of NHE-1 transcription is localized downstream of
      nucleotide -252 in both HepG2 and VSM A7r5 cells but downstream of nucleotide 
      654 in 3T3 cells. Footprinting analysis of the 0.25-kb promoter fragment using
      rat liver nuclear extracts identified 4 protected regions as follows: A, -31 to 
      9; B, -108 to -65; C, -124 to -111; and D, -239 to -215. Internal deletion and
      nucleotide substitutions within regulatory element D revealed its essential role
      for transcription of the human NHE-1 gene in HepG2 and VSM A7r5 cells. DNA
      binding and competition assays using rat liver nuclear extracts indicated that
      regulatory element D is recognized by 5 nuclear activities. Four of these
      activities (designated as NHE-1D1-4) are competed out completely by
      oligonucleotides containing the binding sites of transcription factors CREB, AP3,
      NFY, and other CCAAT box-binding proteins (C/EBP alpha or related proteins). This
      competition profile might be explained by the presence of homology between
      regulatory element D and the consensus sequence of C/EBP as well as the other
      competitor oligonucleotides. The actual relationship between these nuclear
      activities and the C/EBP family of proteins (or other transcription factors)
      remains to be determined.

PMID- 8286418
TI  - Specific 3' sequences flanking a minimal apolipoprotein B (apoB) mRNA editing
      'cassette' are critical for efficient editing in vitro.
AB  - Apolipoprotein B (apoB) mRNA in mammalian intestine undergoes direct conversion
      of cytidine to uridine at nucleotide 6666, generating a UAA stop codon which
      defines the carboxyl-terminus of apoB48. We have identified three distinct
      sequence elements which are required for efficient apoB RNA editing in vitro and
      have defined a 20 nucleotide 'editing cassette' which will support efficient
      editing in the context of a variety of AT-rich apoB mRNA backgrounds. An
      important question remaining to be addressed is whether this cassette can support
      editing in a GC-rich background characteristic of other mRNAs. We demonstrate
      that the context into which the editing cassette is inserted may determine the
      efficiency of editing site utilization. When an editing cassette is placed in the
      context of human albumin mRNA sequence, editing is reduced 6-fold relative to a
      construct of similar length in which the cassette is surrounded by apoB mRNA
      sequence. Chimeric RNA substrates may be efficiently edited, however, when
      albumin sequence resides only 5' of the editing cassette. The data suggest that
      the proximal of an AT-rich, apoB-like, mRNA sequence is only required 3' of the
      editing cassette. These results should prove useful in evaluating the potential
      for editing on mRNAs where similar cassettes can be found.

PMID- 8286419
TI  - Regulation of the expression of the H(+)-ATPase genes PMA1 and PMA2 during growth
      and effects of octanoic acid in Saccharomyces cerevisiae.
AB  - A peak of plasma membrane H(+)-ATPase activity during exponential growth is
      correlated with the expression of the PMA1 gene as monitored by measurements of
      the beta-galactosidase activity from a PMA1-lacZ fusion. This peak of activity is
      also correlated to the content of the H(+)-ATPase protein in yeast plasma
      membrane as shown by quantitative immunodetection. The PMA2-lacZ fusion assay
      indicates that the expression of the PMA2 gene is activated somewhat later during
      exponential phase but under all circumstances its activity remains at least 500
      fold lower than that of the PMA1-lacZ fusion. A slight but significant
      stimulation of ATPase activity by low concentrations of octanoic acid coincides
      with a decrease in the PMA1 gene expression. It is concluded that octanoic acid
      stimulates de PMA1 ATPase activity by posttranslational mechanisms.

PMID- 8286420
TI  - Characterization of singlet oxygen-induced guanine residue damage after
      photochemical treatment of free nucleosides and DNA.
AB  - DNA and free nucleosides were photosensitized with the DNA-binding dyes methylene
      blue (MB) and meso-tetra(4-N-methyl-pyridyl) porphyrin (p-TMPyP) and the non
      binding meso-tetra (4-sulphonatophenyl) porphyrin (TSPP). After light exposure
      DNA was enzymatically digested to nucleosides. Only the guanine residues were
      photodegraded. By measuring optical absorption, at least 20 photoproducts were
      detected. Singlet oxygen (1O2) was involved in induction of all these products
      since D2O enhanced their yields from 4 to 10 times. The photoproducts were the
      same for all sensitizers. However, several photoproducts were found only with DNA
      or only with free 2'-deoxyguanosine. Four of 20 photoproducts were induced both
      in DNA and free 2'-deoxy-guanosine. The yield of the photoproduct 8-oxo-7,8
      dihydro-2'-deoxyguanosine (8-oxo-dG) relative to the degree of 2'-deoxy-guanosine
      degradation depended on which sensitizer was used and on whether nucleosides or
      DNA was exposed. Apparently, DNA structure affected the types of as well as the
      yields of photo-products induced by 1O2.

PMID- 8286421
TI  - Isolation and sequence of a rat glucose-6-phosphate dehydrogenase promoter.
AB  - A 935 bp fragment of the rat glucose-6-phosphate dehydrogenase (G6PDH) gene
      containing promoter activity was isolated using the polymerase chain reaction
      (PCR). This fragment was sequenced and primer extension analysis showed a
      transcription initiation site in agreement with the human and mouse genes.
      Computer analysis of the sequence showed a 60% and 78% similarity to the human
      and mouse G6PDH sequences, respectively. A TATA box element, TTAAAT, was found
      and shown to be 100% similar to the human and mouse TATA box elements. Based on
      sequence comparison, some putative transcriptional regulatory elements were also
      found.

PMID- 8286422
TI  - Secondary thrombin-binding site, glycosaminoglycan binding domain and reactive
      center region of leuserpin-2 are strongly conserved in mammalian species.
AB  - Using a combination of conventional and inverse polymerase chain reaction the
      cDNA structure coding for the thrombin inhibitor leuserpin-2 from rat has been
      determined. The rat genome specifies leuserpin-2 mRNAs differing in their 5'
      untranslated regions probably due to alternative splicing of the primary
      transcript. Comparisons of partial sequences from five different mammalian
      species show that the secondary thrombin binding site, the glycosaminoglycan
      binding domain and the reactive center region of the inhibitor are strongly
      conserved.

PMID- 8286423
TI  - Organization and nucleotide sequence of the secE-nusG region of Streptomyces
      griseus.
AB  - The nusG genes of Streptomyces griseus and Streptomyces coelicolor A3(2) were
      cloned by the DNA-probing method with synthetic oligonucleotides designed on the
      basis of the nucleotide sequence of the nusG gene of Streptomyces virginiae. The
      amino acid sequences of the NusG proteins deduced from the nucleotide sequences
      showed significant homologies to those from a variety of microorganisms.
      Nucleotide sequence analysis of the region upstream of the nusG gene of S.
      griseus revealed the presence of the secE gene, suggesting that secE and nusG are
      organized as an operon as is found in other microorganisms.

PMID- 8286424
TI  - A patient education program.
AB  - Everyday language used by health care professionals in gastroenterology is often
      unfamiliar to patients, regardless of their level of education. Consequently, the
      best efforts to explain diagnoses to patients can result in confusion and anxiety
      instead of understanding. A patient education program was designed in an attempt
      to correct this problem. This article describes how the patient education program
      was developed and implemented.

PMID- 8286425
TI  - Colon cleanout preparations in children and adolescents.
AB  - To determine the effectiveness and associated side effects of a variety of bowel
      cleansing preparations before colonoscopy, 52 children, ages 4 months to 18
      years, were evaluated. Data gathered included type of cleanout preparation used,
      adequacy of the preparations, and side effects. Twenty-two combinations of
      laxatives, lavages, enemas, and rectal suppositories were used. Side effects were
      reported in 90% of patients. In 79% of the patients the colon was clean or clean
      with some liquid feces, allowing a complete examination of the colon. Formed
      feces were present in 21% of the subjects, and cleanout preparations were so
      inadequate in 9% of the subjects that the procedure had to be rescheduled. The
      most effective preparations were X-Prep liquid+Adult Fleet enema, GoLYTELY, and
      GoLYTELY+Adult Fleet enema, all of which allowed a complete examination of the
      colon. Pediatric Fleet ready-to-use enema was the least effective when used
      alone. X-Prep liquid+Adult Fleet enema caused the highest number of side effects
      (18%), while Pediatric Fleet ready-to-use enema alone caused the least (4%). The
      most effective cleanout preparation with the fewest side effects was GoLYTELY,
      used alone or in combination with enemas. These results suggest that many typical
      cleanout preparations yield inadequate results, wasting time or money, and argue
      in favor of the use of more effective preparations with fewer side effects, such
      as GoLYTELY.

PMID- 8286426
TI  - Analysis of aldehyde content of Sekusept Forte solution in automatic disinfection
      of endoscopes.

PMID- 8286428
TI  - Mrs. C.

PMID- 8286427
TI  - Managing esophageal achalasia: medical and nursing implications.
AB  - Achalasia is a motility disorder of the esophagus characterized by total loss of
      esophageal peristalsis and by defective lower esophageal sphincter function. The
      etiology of achalasia is poorly understood. Achalasia occurs across the lifespan,
      but is uncommon in children. Most patients have progressive dysphagia for both
      liquids and solids. This article describes the symptoms of achalasia, its
      diagnosis, and treatment. The emphasis is on primary achalasia. Case studies
      illustrate common findings in patients with achalasia. The importance of patient
      education for effective management of this chronic illness is discussed.

PMID- 8286429
TI  - Endoscopic specimen preparation.

PMID- 8286430
TI  - Pentasa (Mesalamine).
AB  - Pentasa (mesalamine) is a newly released oral 5-aminosalicylic acid capsule
      marketed by Marion Merrel Dow Inc., for the induction of remission and for the
      treatment of mildly to moderately active ulcerative colitis. Ulcerative colitis
      is a chronic inflammatory disease and the most common form of inflammatory bowel
      disease, which is a debilitating and unpredictable group of illnesses affecting
      the gastrointestinal tracts of over 2 million Americans. Pentasa causes few side
      effects and is generally well tolerated.

PMID- 8286431
TI  - It could make a difference.

PMID- 8286432
TI  - Gene discovered for familial colon cancer susceptibility.

PMID- 8286433
TI  - The role of p21ras in receptor tyrosine kinase signaling.
AB  - The notion that ras proteins are required for the stimulation of mitogenesis by
      different receptor tyrosine kinases (RTKs) has spurred researchers to investigate
      the precise role of p21ras in signal transduction. A large number of stimuli can
      drive p21ras in the active conformation, and several proteins that play an
      important role in regulating the GTP/GDP balance on p21ras have been identified.
      Indeed, activation of p21ras has been demonstrated to occur by stimulation of
      guanine nucleotide-releasing proteins (GNRPs) or inhibition of GTPase-activating
      proteins (GAPs). Moreover, a number of SH2-containing proteins have been
      implicated in this signaling pathway, such as shc and sem-5/grb2. On the other
      hand, downstream signaling from p21ras involves an important protein kinase
      cascade. This pathway seems to be conserved in evolution, and analogous routes
      have been described in organisms such as yeast, nematodes, and fruit flies.
      Nevertheless, the direct effector molecule of p21ras that could couple to this
      kinase cascade is still unknown. Some indications have been obtained that suggest
      that this function might be partially performed by p120GAP. This review gives an
      overview of the role of p21ras in signaling from diverse RTKs. Elucidation of
      this pathway will improve our understanding of mitogenic signaling pathways and
      the basis of cancer.

PMID- 8286434
TI  - How does the T-DNA of Agrobacterium tumefaciens find its way into the plant cell
      nucleus?
AB  - Agrobacterium tumefaciens causes the crown gall disease in plants by transferring
      a piece of DNA, the T-DNA, into the genome of the plant cell. The virulence
      protein VirD2, tightly linked to the T-DNA, is thought to direct it to the plant
      cell nucleus and to assist it in integration. The VirD2 protein contains two
      nuclear localization signals (NLS) which are functional both in yeast and in
      plant cells. One signal is located in the N-terminal part of the protein and
      resembles a single-cluster type NLS. The second signal is near the C-terminus and
      is a bipartite type NLS. The involvement of the C-terminal NLS in the entry of
      the T-DNA into the plant cell nucleus was directly tested in vivo.

PMID- 8286435
TI  - Developments in the understanding of the particle structure of tobraviruses.
AB  - Particles of tobraviruses resemble those of tobacco mosaic tobramovirus (TMV) in
      having helical symmetry and in being rod-shaped. However, isolated tobravirus
      coat protein and TMV coat protein respond to changes in the ionic strength and pH
      of the solute in contrasting ways. The types of aggregate formed in solutions of
      coat protein also differ which may be related to differences in the apparent
      mechanism of reconstitution of virus particles from isolated protein and RNA. The
      amino acid sequences of tobravirus and tobramovirus coat proteins have been shown
      to be similar in some regions known to be important for the structure of TMV
      particles. These alignments also show that tobravirus proteins are larger than
      tobramoviral proteins in part because of extra residues at the C-terminus.
      Tobravirus particles give a signal in proton NMR spectroscopy but TMV particles
      do not. The signal is caused by segmental mobility of the C-terminal peptide.
      This difference between TMV and tobraviruses may be related to a property not
      shared by tobraviruses and TMV and it is therefore speculated that the mobile C
      terminal peptide of tobravirus coat proteins may be important in the transmission
      of tobravirus particles by nematode vectors.

PMID- 8286436
TI  - Characterization of different electrophoretic forms of cauliflower mosaic virus
      virions (strain Cabb-S).
AB  - The electrophoretic forms of purified cauliflower mosaic virus (CaMV), strain
      Cabb-S, were examined by electrophoresis on agarose gels. Three populations of
      viral particles were identified: a faster migrating component (the form F) and
      two slower migrating components (the forms S and S'). When the different forms of
      virions, after excision from gels, were subjected to analysis in SDS
      polyacrylamide gel, the fast component consisted of the 37 and 42 kDa coat
      proteins whereas the slow components contained mainly the 39 kDa coat protein.
      However, there was no difference among the nucleic acids associated within the
      three forms. The biological significance of the different components is
      discussed.

PMID- 8286437
TI  - Structural aspects and evolutionary implications of the recognition between tRNAs
      and aminoacyl-tRNA synthetases.
AB  - Recent structural discoveries in the fields of tRNAs and aminoacyl-tRNA
      synthetases (aaRS), such as the existence of two classes of aminoacyl tRNA
      synthetases, the modular character of aaRS with domains homologous to other
      existing proteins, and the absence of direct interactions between the catalytic
      site containing the aminoacid binding pocket and the anticodon point the way to
      an understanding of the origin of the genetic code.

PMID- 8286438
TI  - A novel open reading frame in tobacco mosaic virus genome coding for a putative
      small, positively charged protein.
AB  - From sequence comparisons between the tobramovirus genomes an open reading frame
      (ORF-X) potentially encoding a small, positively charged protein (33- to 45-amino
      acids long) was found to overlap the immediate 3' and 5' sides of the transport
      protein gene and coat protein gene, respectively. In vitro translation of the
      monocistronic artificial transcripts generated with T7 RNA polymerase yielded a
      protein of M(r) 4000 (p4) and an unexpected trypsin-sensitive complex of M(r)
      54,000 that was resistant to reduction with 2-mercaptoethanol but could be
      dissociated by 8 M urea. Assembly of this complex was inhibited completely by
      site-directed mutagenesis within a conserved, positively charged 5-amino-acid
      long segment of the ORF-X protein. After centrifugation in low salt buffer the 54
      kDa complex remained mostly associated with ribosomes. Apparently this complex
      represents a specific aggregate of the p4 product of ORF-X with a protein of
      approximate M(r) 50,000 that is a component of the translation apparatus.

PMID- 8286439
TI  - The thermal stability and decapsidation mechanism of tymoviruses: a differential
      calorimetric study.
AB  - The thermal stability of virions present in purified suspensions of three
      tymoviruses, turnip yellow mosaic virus (TYMV), belladonna mottle virus (BelMV)
      and eggplant mosaic virus (EMV) was investigated by microcalorimetry. Virions are
      less stable than natural empty shells at 4.5 < or = pH < or = 8.5. Polyvalent
      cations present in TYMV stabilize the virions at pH < or = 5.0 only. Virions
      decapsidate in three steps: i) the release of the viral RNA, probably through a
      hole in the capsid; ii) the dissociation of the artificial empty shells thus
      formed; and iii) the denaturation of the dissociated components. An exothermic
      process accompanies the first step. Structural implications are discussed.

PMID- 8286440
TI  - Evidence for a phosphoenolpyruvate dependent sugar-phosphotransferase system in
      the mollicute Acholeplasma florum.
AB  - In order to confirm the presence of a phosphoenolpyruvate (PEP)-dependent sugar
      phosphotransferase system (PTS) in the mollicute Acholeplasma florum we studied
      the ability of cell free extracts of this organism to phosphorylate glucose
      and/or fructose in the presence of PEP. We also cloned and sequenced a DNA
      fragment coding for a putative polypeptide showing significant similarity with
      the enzyme II of the beta-glucoside PTS of Escherichia coli. Taken together,
      these results show that A florum possesses a fructose-PTS, but not a glucose-PTS,
      and that the amino acid sequence deduced from the DNA fragment is related to beta
      glucoside and sucrose enzymes II of PTS from various bacteria.

PMID- 8286441
TI  - Spontaneous dimerization of retroviral MoMuLV RNA.
AB  - The genome of the Moloney murine leukemia virus (MoMuLV) is composed of two
      identical RNA molecules joined at their 5' ends by the dimer linkage structure
      (DLS). Dimerization sequences are located within the PSI encapsidation domain. We
      present here an overview of the work we have performed on spontaneous
      dimerization of a MoMuLV RNA fragment encompassing the PSI domain in order to
      understand the mechanism by which retroviral RNA dimerization takes place. We
      present kinetical, thermodynamical and conformational evidence which leads to the
      conclusion that the PSI domain is a structurally independent domain and that
      conformational changes are triggered by the dimerization process. We conclude
      that at least one particular region (nucleotides 278-309) of the RNA is directly
      involved in the process while the conformation of some other regions is changed
      probably because of a long-range effect.

PMID- 8286442
TI  - Plant 'pathogenesis-related' proteins and their role in defense against
      pathogens.
AB  - The hypersensitive reaction to a pathogen is one of the most efficient defense
      mechanisms in nature and leads to the induction of numerous plant genes encoding
      defense proteins. These proteins include: 1) structural proteins that are
      incorporated into the extracellular matrix and participate in the confinement of
      the pathogen; 2) enzymes of secondary metabolism, for instance those of the
      biosynthesis of plant antibiotics; 3) pathogenesis-related (PR) proteins which
      represent major quantitative changes in soluble protein during the defense
      response. The PRs have typical physicochemical properties that enable them to
      resist to acidic pH and proteolytic cleavage and thus survive in the harsh
      environments where they occur: vacuolar compartment or cell wall or intercellular
      spaces. Since the discovery of the first PRs in tobacco many other similar
      proteins have been isolated from tobacco but also from other plant species,
      including dicots and monocots, the widest range being characterized from
      hypersensitively reacting tobacco. Based first on serological properties and
      later on sequence data, the tobacco PRs have been classified in five major
      groups. Group PR-1 contains the first discovered PRs of 15-17 kDa molecular mass,
      whose biological activity is still unknown, but some members have been shown
      recently to have antifungal activity. Group PR-2 contains three structurally
      distinct classes of 1,3-beta-glucanases, with acidic and basic counterparts, with
      dramatically different specific activity towards linear 1,3-beta-glucans and with
      different substrate specificity. Group PR-3 consists of various chitinases
      lysozymes that belong to three distinct classes, are vacuolar or extracellular,
      and exhibit differential chitinase and lysozyme activities. Some of them, either
      alone or in combination with 1,3-beta-glucanases, have been shown to be
      antifungal in vitro and in vivo (transgenic plants), probably by hydrolysing
      their substrates as structural components in the fungal cell wall. Group PR-4 is
      the less studied, and in tobacco contains four members of 13-14.5 kDa of unknown
      activity and function. Group PR-5 contains acidic-neutral and very basic members
      with extracellular and vacuolar localization, respectively, and all members show
      sequence similarity to the sweet-tasting protein thaumatin. Several members of
      the PR-5 group from tobacco and other plant species were shown to display
      significant in vitro activity of inhibiting hyphal growth or spore germination of
      various fungi probably by a membrane permeabilizing mechanism.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8286443
TI  - UDP-glucose sterol beta-D-glucosyltransferase, a plasma membrane-bound enzyme of
      plants: enzymatic properties and lipid dependence.
AB  - UDP-glucose sterol beta-D-glucosyltransferase (UDPG-SGTase) catalyzes the
      glucosylation of plant sterols. This enzyme has been shown to be membrane-bound,
      most of its activity being associated with plasma membrane in etiolated maize
      coleoptiles. After solubilization with detergents, total delipidation and
      purification, kinetic studies performed with a purified enzyme preparation in the
      presence of detergent and soybean phosphatidylcholine (PC) strongly suggest an
      ordered bi-bi mechanism for the glucosylation of sterols. A reduced sulfhydryl
      group and an arginyl residue were shown to be essential for activity. Lipid
      dependence studies have been performed on the delipidated enzyme in two systems:
      a micellar one composed of a mixture of enzyme, detergent and phospholipids and
      another one where the enzymatic activity was reconstituted in unilamellar lipid
      vesicles. In both systems it was shown that the UDPG-SGTase activity was
      stimulated to a large extent by negatively charged phospholipids. Enzymatic
      assays were performed with membrane fractions originating from plants whose
      sterol content was profoundly modified following treatment with a sterol
      biosynthesis inhibitor. Results showed that the sterol glucosylating activity was
      strongly inhibited in these fractions in accordance with sterol substrate
      specificity studies. All these results show that the UDPG-SGTase is exquisitely
      sensitive to its lipid environment. Physiological implications of these data are
      discussed in the light of the putative role of sterols in the plant cell.

PMID- 8286444
TI  - Higher plant microtubule-associated proteins: in vitro functional assays.
AB  - Microtubule-associated proteins (MAPs) can account for the assembly and
      stabilization of microtubules at low tubulin concentration, for their ability to
      interact with other microtubules and/or cytoskeletal polymers or organelles and
      also for regulating microtubule anchoring and bundling properties. The data
      concerning higher plant MAPs remain limited so far to a few examples. Motor MAPs
      such as dynein or kinesin remain poorly documented in plants and are not to be
      discussed here. In this manuscript, the attention is focused on structural MAPs
      which co-assemble with tubulin during microtubule assembly. Using taxol, we
      developed an assay where higher plant microtubules were induced to self-assemble
      in a cytosolic extract of maize cultured cells and could be used as a native
      matrix for the isolation of putative higher plant MAPs. Seven polypeptides with
      molecular masses ranging between 60-125 kDa were found in this MAP-enriched
      fraction. These putative plant MAPs were shown to co-assemble with pig brain
      tubulin through two cycles of temperature-dependent assembly-disassembly. They
      were able to initiate and promote MAP-free tubulin assembly under conditions of
      non-efficient self-assembly and induced bundling of both plant and neural
      microtubules. One of these polypeptides (83 kDa) was found to be immunologically
      related to neural tau, suggesting the presence of common epitopes between neural
      and plant MAPs. Such epitopes may be present at the microtubule-binding domains,
      as the higher plant MAPs co-assemble with brain tubulin. Plant microtubules
      exhibit an important in situ bundling activity, as in cortical or pre-prophase
      band arrays, or during the drastic reorganization of the cytoskeleton during
      mitosis induction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286445
TI  - Mutational analysis of AUG codons of cowpea mosaic virus M RNA.
AB  - The involvement of the AUG codons at positions 115, 161, 512 and 524 in
      translation and infectivity of cowpea mosaic virus M RNA was studied. Mutations
      were introduced in each of these codons in a full length cDNA clone of M RNA and
      the effect of the mutations was examined by translation from in vitro transcripts
      of these mutant cDNAs in rabbit reticulocyte lysates and by checking the
      replication of these transcripts in the presence of B RNA in cowpea protoplasts
      and plants. It was found that AUG115, at the beginning of an open reading frame
      (ORF) for a putative 2-kDa protein, can be used in vitro to initiate translation,
      but mutation of this AUG codon in the M RNA does not affect the ability of the
      virus to infect cowpea plants. AUG161, located at the beginning of the large ORF,
      was shown to be essential for expression of the large 105-kDa polyprotein and for
      replication of M RNA. Translation of the second 95-kDa polyprotein was found to
      start at AUG512. Upon mutation of this AUG codon efficient initiation of
      translation occurred at AUG524. Results with M RNAs that lack AUG512 and/or 524
      indicate that an intact 95-kDa polyprotein is not required for replication of M
      RNA but that this protein has an essential function in cell-to-cell movement of
      the virus.

PMID- 8286446
TI  - Comparison of in vivo reactivation, in vitro reactivation, and polymerase chain
      reaction for detection of latent pseudorabies virus infection in swine.
AB  - The following methods were compared for their ability to detect latent
      pseudorabies virus in 24 pigs that had been experimentally infected with virulent
      pseudorabies virus: 1) in vivo reactivation by dexamethasone administration, 2)
      in vitro reactivation by 5 different techniques of explant culture or
      cocultivation of trigeminal ganglia, and 3) detection of pseudorabies virus
      genome in tissue digests of tonsils or trigeminal ganglia using the polymerase
      chain reaction. Reactivation of pseudorabies virus by administration of
      dexamethasone was attempted in 12 of 24 pigs in an effort to determine if this
      procedure would affect the detection of latent pseudorabies virus by any of the
      subsequent in vitro methods. Detection of latent virus by the polymerase chain
      reaction with trigeminal ganglia was the most successful method (24/24 were
      positive). The next most successful method was in vivo reactivation through the
      administration of dexamethasone (10/12 [83%] were positive). Only 1 in vitro
      reactivation technique, cocultivation involving digestion of the trigeminal
      ganglia with trypsin and collagenase and the addition of a hypomethylating agent
      to the medium, yielded positive results (5/24 [21%] were positive). The
      polymerase chain reaction performed on tissue digests of tonsils was much less
      effective (2/24 [8%] were positive) than it was with trigeminal ganglia.
      Reactivation by dexamethasone did not appear to have any effect on the subsequent
      detection of latency by any of the methods tested.

PMID- 8286447
TI  - ELISA method for detection of influenza A infection in swine.
AB  - An antigen-capture enzyme-linked immunosorbent assay (ELISA) was developed to
      monitor virus shedding associated with experimental infection with a field strain
      of swine influenza in pigs. The assay consisted of a monoclonal anti
      nucleoprotein capture antibody and a biotinylated rabbit anti-influenza A (H1N1)
      sandwich antibody. The antigen-capture system was capable of detecting as little
      as 1 ng/ml purified virus. The ELISA system surpassed egg cultivation procedures
      in the detection of low levels of shedding virus. Egg cultivation procedures
      indicated that most viral shedding had ceased by day 10 postinfection. In
      contrast, antigen-capture ELISA still showed an ongoing presence of viral
      antigen. A virus-capture ELISA, using this capture-sandwich antibody system, is
      equivalent in sensitivity to conventional egg inoculation procedures for the
      detection of the early phases of virus shedding. The automative potential of an
      ELISA-based system coupled with a substantially reduced assay time requirement
      give this virus-capture ELISA a distinct advantage over other cell culture or egg
      based diagnostic techniques.

PMID- 8286448
TI  - PCR detection of group A bovine rotaviruses in feces.
AB  - A polymerase chain reaction (PCR) protocol has been developed for identification
      of bovine group A rotavirus infection in feces. Primers (20mers) complementary to
      3' ends of double-stranded RNA genome segment 6 of bovine rotavirus NCDV strain
      were synthesized and used in PCR. Bovine rotavirus RNA from infected cell culture
      was employed to optimize the PCR protocol. Rotavirus-negative fecal samples were
      spiked with known quantities of bovine rotavirus, and the sensitivity of the PCR
      assay was determined. Fecal samples were extracted with phenol and treated to
      eliminate unidentified PCR inhibitor(s) in feces, and PCR was performed. PCR
      products were either visualized on ethidium bromide-stained agarose gels or
      detected by chemiluminescent hybridization. The sensitivity of the assay was 6 x
      10(4) viral particles/ml of feces with ethidium bromide-stained agarose gel
      visualization or 6 x 10(2) viral particles/ml of feces with chemiluminescent
      hybridization. The PCR assay was applied to 18 fecal specimens from clinical
      cases. All 16 clinical samples that were positive for rotavirus by enzyme-linked
      immunosorbent assay (ELISA) or by ELISA and electron microscopy (EM) were
      positive by PCR. The 2 samples that were rotavirus negative by ELISA or by ELISA
      and EM were also negative on PCR analysis.

PMID- 8286449
TI  - Laboratory investigation of PRRS virus infection in three swine herds.
AB  - Late in 1991, an enveloped RNA virus (now called porcine reproductive and
      respiratory syndrome [PRRS] virus) was identified as the etiologic agent for
      mystery swine disease. In 1992, laboratory procedures for the diagnosis of this
      disease evolved rapidly, and veterinary diagnosticians started applying these
      tests to field cases. This report is written from the perspective of veterinary
      laboratory diagnosticians and utilizes 3 case studies to define the advantages
      and disadvantages of the various available diagnostic laboratory PRRS test
      procedures in different clinical situations. The diagnostic procedures currently
      used in our laboratory for investigating PRRS are pathologic examination,
      serologic testing, fluorescent antibody (FA) testing, and virus isolation.
      Interstitial pneumonia, characterized by mononuclear cell infiltration of
      alveolar walls with normal airway epithelium, is a hallmark lesion for the
      disease, especially in neonatal pigs with respiratory distress. Interstitial
      pneumonia is not a specific lesion and must be coupled with other tests to verify
      PRRS virus infection. Demonstration of seroconversion is helpful, especially in
      sows that have experienced reproductive failure. The indirect FA test detects
      antibody sooner than the serum neutralization test and will likely become the
      serologic test of choice. The direct FA test on fresh tissue utilizes monoclonal
      antibody and is useful for investigating PRRS virus-associated pneumonia. Virus
      isolation utilizing swine alveolar macrophages has also been a useful diagnostic
      procedure. All of the above tests have been universally unrewarding when applied
      to aborted, mummified, or stillborn piglets.

PMID- 8286450
TI  - Evaluation of serological pseudorabies tests for the detection of antibodies
      during early infection.
AB  - Six enzyme-linked immunosorbent assays, a latex agglutination test, and the
      standard microtitration serum virus neutralization test were compared for their
      ability to detect antibodies against pseudorabies virus (PRV) during the early
      stages of infection. Thirty-five pigs were infected intranasally with 10(5)-10(7)
      TCID50 of either the Iowa 4892 pneumotropic or the Becker strain of PRV. Blood
      samples were drawn from experimentally inoculated animals on days 4-10, 14, and
      21 postchallenge. Test sensitivity estimates and comparisons among tests were
      made for each sampling day over the 21-day monitoring period. Results of this
      study demonstrated differences among tests in 1) the time from inoculation to
      initial antibody detection, 2) the time to detect > or = 95% of the infected
      pigs, and 3) the time from initial antibody detection to determination of > or =
      95% as positive. By day 10 postchallenge, no statistically significant difference
      in diagnostic sensitivity was observed among the 8 tests compared in the study.

PMID- 8286451
TI  - Efficacy of a deletion mutant bovine herpesvirus-1 (BHV-1) vaccine that allows
      serologic differentiation of vaccinated from naturally infected animals.
AB  - Fifteen bovine herpesvirus-1 (BHV-1)-negative calves were vaccinated
      intramuscularly with 10(7.4) plaque-forming units of a double-deletion BHV-1
      mutant (IBRV(NG)dltkdlgIII), and 6 remained as nonvaccinated controls. Thirty
      days after vaccination, the animals were challenged by nasal instillation of
      10(8.2) CCID50 of a virulent BHV-1 strain (Cooper). The vaccinated calves were
      protected against wildtype virus challenge as demonstrated by clinical
      evaluation. Most of the vaccinates developed only a mild rhinitis (lasting an
      average of 6.5 days) with almost no systemic symptoms, whereas the controls
      developed a serious illness characterized by rhinitis (mean = 11.5 days),
      conjunctivitis, hyperthermia, apathy, loss of appetite, and dyspnea. The
      vaccinates also shed significantly less virus and for a shorter period of time
      (mean = 5.5 days) than the controls (mean = 9 days). Thirty days after
      vaccination, the vaccinates were negative in an anti-gIII specific blocking
      enzyme-linked immunosorbent assay (ELISA), despite the fact that most of them had
      developed neutralizing antibodies (serum neutralization titers ranging from 1:2
      to 1:16). Seroconversion to gIII was detected as early as 7 days postinfection
      (dpi). Fourteen days after the challenge, all the animals exposed to wildtype BHV
      1 had developed anti-gIII antibodies and were positive in this differential
      serologic test. Six controls plus 8 vaccinates kept in isolation were still
      positive to gIII when tested at 75 dpi. The use of the IBRV(NG)dltkdlgIII strain
      in conjunction with an anti-gIII specific blocking ELISA kit represents a
      powerful tool for BHV-1 control/eradication programs.

PMID- 8286453
TI  - Optimization of polymerase chain reaction for the detection of Borrelia
      burgdorferi in biologic specimens.
AB  - This study describes the use of a newly constructed set of primers that amplifies
      an 85-base pair (bp) segment of Borrelia burgdorferi chromosomal DNA. This 85-bp
      product is not produced when other Borrelia species, Leptospira, or other
      bacteria are subjected to polymerase chain reaction (PCR). We also describe a
      rapid method of optimizing the amplification of B. burgdorferi DNA from canine
      ethylenediaminetetraacetic acid-treated blood and urine samples that circumvents
      some of the problems encountered due to low number of spirochetes in clinical
      specimens and that removes inhibiting substances, which improves the PCR
      diagnosis of canine Lyme borreliosis.

PMID- 8286452
TI  - Microdilution antimicrobial susceptibilities of selected gram-negative veterinary
      bacterial isolates.
AB  - Gram-negative bacterial isolates (635) obtained from routine submissions to the
      Oklahoma Animal Disease Diagnostic Laboratory during 1983-1987 were tested for
      antimicrobial susceptibility. Minimal inhibitory concentrations (MICs) were
      determined for the following antimicrobials using commercially prepared
      microdilution assay materials: ampicillin, cephalothin, chloramphenicol,
      erythromycin, gentamicin, kanamycin, oxytetracycline, penicillin G,
      spectinomycin, sulfachlorpyridazine, sulfadimethoxine, and tylosin. Results for
      isolates from cattle, dogs, horses, and pigs are presented. In only a few
      instances were differences in MICs apparent among bacterial isolates from
      different tissues. Aminocyclitol MICs for equine uterine isolates of Klebsiella
      pneumoniae differed from MICs for isolates from other tissues, and ampicillin,
      kanamycin, and spectinomycin MICs for bovine fecal isolates of Escherichia coli
      differed from MICs for isolates obtained from other tissues. In several
      instances, bimodal distribution of susceptibilities was apparent for ampicillin,
      kanamycin, and/or oxytetracycline. There was also a bimodal distribution pattern
      for erythromycin against Pasteurella haemolytica of bovine origin.

PMID- 8286454
TI  - Systemic Pasteurella haemolytica infection as a rare sequel to avirulent live
      Pasteurella haemolytica vaccination in cattle.
AB  - Eleven cases of systemic Pasteurella haemolytica infection in cattle were
      identified from routine diagnostic laboratory submissions during the falls of
      1988, 1989, and 1991. All cases came with a history of recent vaccination with an
      avirulent live culture P. haemolytica product. Nine of 11 cases involved cattle
      vaccinated between 2 and 18 days previously with this product. Ten of 11 cases
      involved 182-227-kg beef calves that were vaccinated between September and
      November during routine processing for entry into feedlots. The morbidity and
      mortality was generally low. The major pathologic findings included meningitis,
      injection site abscessation and/or cellulitis, and polyarthritis. Systemic
      infection was indicated in all cases by the isolation of P. haemolytica from 2 or
      more organs or distinct anatomical sites. In 6 cases, the vaccine injection site
      was cultured, and in all 6 cases, P. haemolytica was isolated. Three separate P.
      haemolytica isolates from 2 cases were further studied by restriction enzyme
      analysis (REA). These isolates were from tissues with suppurative inflammation,
      including the brain, joint, and injection site. The REA patterns of each of these
      3 isolates were identical to the REA pattern of the vaccine masterseed, which
      strongly suggested that the organisms causing systemic infection were the same as
      the organism used to produce the vaccine. Because the overall incidence was quite
      low, other factors, such as stress, probably played a major role in the
      expression of this syndrome.

PMID- 8286455
TI  - Equine abortion and stillbirth in central Kentucky during 1988 and 1989 foaling
      seasons.
AB  - Pathologic and microbiologic examinations were performed on 1,211 aborted equine
      fetuses, stillborn foals, and placentas from premature foals in central Kentucky
      during the 1988 and 1989 foaling seasons to determine the causes of reproductive
      loss in the mare. Placentitis (19.4%) and dystocia-perinatal asphyxia (19.5%)
      were the 2 most important causes of equine reproductive loss. The other causes
      (in decreasing order) were contracted foal syndrome and other congenital
      anomalies (8.5%), twinning (6.1%), improper separation of placenta (4.7%),
      torsion of umbilical cord (4.5%), placental edema (4.3%), equine herpesvirus
      abortion (3.3%), bacteremia (3.2%), fetal diarrhea (2.7%), other placental
      disorders (total of 6.0%), and miscellaneous causes (1.6%). A definitive
      diagnosis was not established in 16.9% of the cases submitted. Streptococcus
      zooepidemicus, Escherichia coli, Leptospira spp., and a nocardioform actinomycete
      were organisms most frequently associated with bacterial placentitis, and
      Aspergillus spp. was the fungus most often noted in mycotic placentitis. No viral
      placentitis was noticed in this series. Dystocia-perinatal asphyxia was mostly
      associated with large foals, maiden mares, unattended deliveries, and
      malpresentations. The results of this study indicate that in central Kentucky,
      the noninfectious causes of equine reproductive loss outnumber the infectious
      causes by an approximate ratio of 2:1, placental disorders are slightly more
      prevalent than nonplacental disorders, Leptospira spp. and a nocardioform
      actinomycete are 2 new important abortifacient bacteria in the mare, the
      occurrence of contracted foal syndrome is unusually frequent, the incidence of
      twin abortion has sharply declined, and torsion of the umbilical cord is an
      important cause of abortion in the mare.

PMID- 8286456
TI  - Paratuberculosis in farmed deer: case reports and DNA characterization of
      isolates of Mycobacterium paratuberculosis.
AB  - Mycobacterium paratuberculosis was isolated from farmed deer in New Zealand on 21
      occasions over a 7-year period. The number of cases increased during the last 3
      years of the study. Clinical paratuberculosis was observed in 5 deer, 3 other
      cases came from grossly normal animals that reacted to a tuberculin skin test,
      and the remaining 13 animals had tuberculous lesions that were identified at meat
      inspection. Pathologic features of the lesions in these 13 cases included
      necrosis and mineralization in lymph nodes draining the gastrointestinal tract.
      The histologic changes in these lesions were very similar to those caused by
      Mycobacterium bovis and members of the M. avium complex. Characterization of 20
      of the isolates of M. paratuberculosis by restriction endonuclease analysis and
      DNA hybridization revealed that 3 of these isolates were identical to New Zealand
      sheep isolates and 17 were the same as cattle isolates. The source of the cervine
      infections was not determined.

PMID- 8286457
TI  - Detection of serum antibody responses in cattle with natural or experimental
      Neospora infections.
AB  - Parasite-specific antibody responses were detected using an indirect fluorescent
      antibody (IFA) test in cattle that were naturally or experimentally infected with
      Neospora parasites. The test was developed using Neospora tachyzoites isolated
      from an aborted bovine fetus and grown in bovine cell cultures (isolate BPA1). In
      all cases, infections were confirmed by the identification of Neospora
      tachyzoites and/or bradyzoite cysts in fetal or calf tissues using an
      immunoperoxidase test procedure. Fifty-five naturally infected cows that aborted
      Neospora-infected fetuses had titers of 320-5,120 at the time of abortion. The
      titer of 6 cows that were serologically monitored over a prolonged period
      decreased to 160-640 within 150 days after they aborted infected fetuses. Two of
      the cows showed an increase in their Neospora titers during their subsequent
      pregnancy, and they gave birth to congenitally infected calves that had
      precolostral titers of 10,240-20,480. Postcolostral titers of these calves and of
      4 other calves with congenital Neospora infections were all > or = 5,120, whereas
      calves with no detectable parasites had titers < or = 160. Two pregnant heifers
      that were experimentally infected with the BPA1 isolate at approximately 120 days
      gestation seroconverted to Neospora antigens within 9 days and developed peak
      titers of 5,120 and 20,480 within 32 days of infection. The fetus taken by
      caesarean section 32 days postinfection from 1 heifer and the full-term calf born
      to the other had Neospora titers of 640 and 10,240, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8286458
TI  - Detection of Neospora caninum in tissue sections using a murine monoclonal
      antibody.
AB  - A murine monoclonal antibody (MAb 6G7), isotype IgG2a, produced against
      tachyzoites of Neospora caninum (isolate NC-1) reacted specifically with
      tachyzoites of N. caninum in an indirect immunofluorescent antibody test. MAb 6G7
      did not react with tachyzoites of Toxoplasma gondii, sporozoites of Isospora
      suis, Eimeria bovis, or E. tenella, or merozoites of E. bovis in the indirect
      immunofluorescent antibody test. MAb 6G7 reacted positively with both tachyzoites
      and bradyzoites of N. caninum in an avidin-biotin peroxidase complex
      immunohistochemical test on formalin-fixed paraffin-embedded tissues. No reaction
      was observed with the following: tachyzoites and bradyzoites of T. gondii, T.
      gondii-like parasites, or Hammondia hammondi; bradyzoites of Frenkelia microti;
      schizonts and merozoites of Sarcocystis-like organisms; schizonts, sarcocysts,
      and oocysts/sporocysts of S. cruzi; schizonts and merozoites of S. canis;
      schizonts of S. hirsuta, S. tenella, and S. capracanis; merozoites of S. neurona
      and S. neurona-like organisms, E. bovis, or Haemoproteus sp.; bradyzoites and
      merozoites of S. montanaensis; bradyzoites of S. odocoileocanis, S. cruzi, and S.
      tenella; meronts, sexual stages, and caryocysts of Caryospora sp. and C.
      bigenetica; micromerozoites, macromerozoites, and schizonts of Hepatozoon canis;
      sporozoites, sexual stages, and oocysts of Cryptosporidium parvum and C. baileyi;
      trophozoites of Monocystis lumbrici, Tritrichomonas foetus, and Balantidium coli;
      tissue cysts and bradyzoites of Besnoitia sp. and B. jellisoni; amastigotes of
      Leishmania sp.; and trophic theronts of Ichthyopthirius multifilis. MAb 6G7
      reacted with tachyzoites and bradyzoites of N. caninum in natural and
      experimental infections in dogs, cattle, mice, rats, sheep, and goats, indicating
      that host origin of the tissues did not affect the performance of the test.

PMID- 8286459
TI  - Neuroaxonal dystrophy in a group of related cats.
AB  - A syndrome resembling previously described feline hereditary neuroaxonal
      dystrophy (FHND) was diagnosed in a litter of cats. The disorder was
      characterized by a sudden onset of hind limb ataxia that slowly progressed to
      hind limb paresis and paralysis. The cats were between 6 and 9 months old when
      clinical signs were first noted. Histologically, there was marked ballooning of
      axonal processes, with spheroid formation and vacuolation in specific regions of
      the brain and spinal cord. Some dystrophic axons contained a central periodic
      acid-Schiff (PAS)-positive core. Neuronal loss and gliosis were seen in certain
      brain stem nuclei, spinal cord nuclei, and the cerebellum. Ultrastructurally,
      there was hypomyelination and dysmyelination of affected axons. The PAS-positive
      core in dystrophic axons corresponded ultrastructurally with accumulations of
      electron-dense, flocculent, amorphous material. In addition, these axons
      contained membrane-bound osmiophilic bodies and large nonmembrane-bound vacuoles.
      The syndrome in this report differs from the previously described FHND in that no
      inner ear involvement was seen and onset of clinical signs occurred at a later
      age. In addition, although some of the affected cats did have diluted coat
      colors, abnormal coat color was not always associated with clinical disease. This
      disease is similar to juvenile neuroaxonal dystrophy in children and to
      neuroaxonal dystrophies described in horses, dogs, cattle, and sheep.

PMID- 8286460
TI  - Pathology of renal dysplasia and bladder aplasia-hypoplasia in a flock of sheep.
AB  - Congenital renal disease was detected in a flock of sheep in the English Midlands
      over 2 successive years (1982 and 1983). A Suffolk ram was removed from the flock
      and test mated to unrelated Suffolk ewes in another flock; 14 of the resulting 43
      lambs born in 1984 had an identical congenital renal disease. Kidneys were
      examined microscopically from 60 clinically affected neonatal lambs. Kidneys from
      7 of the 60 clinically affected neonatal lambs (1, 1983; 6, 1984) were examined
      ultrastructurally and compared with kidneys from 3 healthy unrelated neonatal
      lambs. Most affected lambs examined (52/60) had bilaterally small kidneys (< or =
      2 g) with fine intracortical cysts and distinct cortical and medullary zones.
      Kidneys were either grossly normal (3/60 lambs) or multicystic and of normal size
      to markedly enlarged (5/60 lambs). The bladder was absent or vestigial in most
      lambs. Microscopically, poorly differentiated ("primitive") tubules were present
      in renal cortex and medulla. Proximal convoluted tubules, where present, were
      formed by epithelial cells with distinctive round weakly autofluorescent
      intracytoplasmic inclusions with the ultrastructural appearance of atypical
      lysosomes. Loops of Henle, distal convoluted tubules, and juxtaglomerular
      peripolar cell complexes were largely absent. Glomerular changes were minimal.
      Cystic dilatation of nephrons was restricted to proximal convoluted tubules lined
      by vacuolated epithelium. This distinctive congenital renal dysplasia of sheep
      was most likely inherited as a dominant trait with complete penetrance.

PMID- 8286461
TI  - Estrogenic activity in forages: diagnostic use of the classical mouse uterine
      bioassay.
AB  - The classical mouse uterine bioassay was evaluated and adapted for routine
      diagnostic use in response to requests for evaluation of forages suspected of
      being estrogenic. Forages were extracted in acetone or 10% ethanol in acetone
      (v/v). Extracts were mixed with ground corn-based mouse feed. Immature female
      mice (n = 3/group) were fed a total of 100 g of the ground feed for 5 days. Body
      weights were monitored before and after the trial. After 6 days, the mice were
      euthanized and uterine weights were determined. Mean uterine weights were
      compared using 1-way analysis of variance with preselected contrasts for
      individual means. Selected uteruses were fixed in 10% neutral buffered formalin
      for histologic examination. Control feeds, diethylstilbestrol (DES), estradiol,
      coumestrol, feeds with no reported estrogenic properties, and a feed that caused
      hyperestrogenism in cattle were tested. Moderate levels of estrogenic compounds
      resulted in dose-responsive uterine enlargements (10-270 ppm coumestrol over 5
      days). Extremely high levels of estrogen frequently resulted in feed refusal and
      lack of uterine enlargement (10 ppm DES, 100 ppm estradiol). Diagnostically
      significant estrogenic activity was recovered from the feed known to have been
      estrogenic in cattle. The classical mouse uterine bioassay was relatively
      inexpensive, quick, repeatable, and capable of detecting clinically relevant
      coumestrol levels in hay.

PMID- 8286462
TI  - Circovirus-like infection in a pigeon.

PMID- 8286463
TI  - Serologic survey for Lelystad and VR-2332 strains of porcine respiratory and
      reproductive syndrome (PRRS) virus in US swine herds.

PMID- 8286464
TI  - Competitive ELISA for serodiagnosis of bluetongue: a refinement.

PMID- 8286465
TI  - Immunohistochemical detection of CD3 antigen (pan T marker) in canine lymphomas.

PMID- 8286466
TI  - Time and temperature survivability of PRRS virus in serum and tissues.

PMID- 8286467
TI  - Diagnosis of enteritis and enterotoxemia due to Clostridium difficile in captive
      ostriches (Struthio camelus).

PMID- 8286468
TI  - Minimum inhibitory concentrations of bacteria isolated from septicemia and
      airsacculitis in ducks.

PMID- 8286469
TI  - The thermal resistance of Mycobacterium paratuberculosis in raw milk under
      conditions simulating pasteurization.

PMID- 8286470
TI  - Nocardiosis in a llama.

PMID- 8286471
TI  - Hepatoblastoma in an equine fetus.

PMID- 8286472
TI  - Myofibroblastic sarcoma originating at the site of rabies vaccination in a cat.

PMID- 8286473
TI  - Metastatic adenocarcinoma of the mammary gland in a Pere David's deer.

PMID- 8286474
TI  - Hereditary hypermetria in shorthorn cattle.

PMID- 8286475
TI  - Ubiquitin immunocytochemistry of spinal cord in an inherited porcine motor neuron
      disease.

PMID- 8286476
TI  - Comparison of three diagnostic tests for Dirofilaria immitis in a low-incidence
      area.

PMID- 8286477
TI  - Spontaneous encephalitozoonosis in an experimental group of guinea pigs.

PMID- 8286478
TI  - Toxicosis due to microcystin hepatotoxins in three Holstein heifers.

PMID- 8286479
TI  - Fumonisin contamination of the 1991 Indiana corn crop and its effects on horses.

PMID- 8286480
TI  - Porcine reproductive and respiratory syndrome.

PMID- 8286481
TI  - [Changes in lipoglycoprotein metabolism in toxic fatty liver].
AB  - BACKGROUND: A number of agents that produce liver injury also cause the
      accumulation of an abnormal amount of fat, predominantly triglycerides (TGs) in
      the parenchymal cells. Fatty liver (FL) is the result of an hepatocyte imbalance
      between the rate of synthesis and output of TGs into the plasma. TGs are not
      secreted as such, but combined with a glycoprotein moiety, and particularly with
      the very low density lipoproteins (VLDLs). This fraction is involved in the
      transport of hepatic TGs to extrahepatic tissues. FL can be induced by either
      acute or chronic administration of ethanol (EtOH), and/or several haloalkanes
      (carbon tetrachloride, CCl4; 1.2-dichloroethane, DCE; 1.1.2.2-tetrachloroethane,
      TTCE), both in laboratory animals and in man. Since the pathogenesis of this
      disease is a crucial problem, as yet undefined, the purpose of this article is to
      summarize the studies which have unraveled some of the mechanisms involved in FL,
      particularly the role played by impaired lipoglycoproteins (LGP) metabolism in
      rat liver. DISCUSSION: An important element in the pathogenesis of EtOH- and
      haloalkanes-induced FL is the impairment of hepatic secretion of VLDLs, which
      occurs soon after poisoning. Various steps of the secretory pathway are probably
      involved in the expression of such damage. The intoxication of rats with these
      xenobiotics leads to an early impairment of the hepatocyte system responsible for
      terminal glycosylation and maturation of LGP at the level of three different
      subfractions (F1, F2 and F3) of purified Golgi apparatus (GA). The earliest
      functional change is a block of LGP transit through the GA cisternae and
      vesicles, both in isolated hepatocyte model and in the whole animal. The
      glycosylation of LGP is a multistep process which starts in the rough endoplasmic
      reticulum (RER), and comes to its end in the GA. Dolichols (Dol) are a family of
      long-chain polyisoprenoid alcohols, present either as neutral free-Dol and
      dolichyl-phosphate (Dol-P). The latter acts as a glycosyl carrier across the RER
      membranes in the initial steps of LGP biosynthesis. Nearly all the other
      reactions occur in GA, where free-Dol have a role either in terminal LGP
      processing or in their secretion into the blood stream. Several investigations
      indicated that both EtOH and haloalkanes (CCl4, DCE, and TTCE) may selectively
      and precociously impair the total microsomes (TM) and GA pool of Dol,
      particularly in F1. Lipid peroxidation appears to be the fundamental mechanism
      involved. CONCLUSIONS: Such results, obtained in several works, point out a key
      role played in FL by selective impairment of MT and GA processes which provide
      for the synthesis, maturation and release of hepatic LGP.

PMID- 8286482
TI  - [Eating behavior and energy expenditure].
AB  - The relationships between the resting energy expenditure (REE), measured by
      indirect calorimetry, and eating behavior, assessed by the "Three Factor Eating
      Questionnaire" were evaluated. The study was carried out in a group of healthy
      never-obese subjects and in two groups of formerly obese people, who have
      maintained a normal weight for more than two years. The subjects of the first
      formerly obese group had brought their body weight to normal by dieting. The
      second one comprised subjects following biliopancreatic diversion for obesity
      (BPD) in the long term, who maintain a normal weight because of the intestinal
      malabsorption due to the operation regardless of food consumption. In comparison
      with the other subjects, significantly higher cognitive restraint score values
      were observed in the post-diet subjects. Furthermore, a negative significant
      correlation between cognitive restraint and REE was found in the non operated
      subjects, while such correlation was not present in the BPD subjects. Therefore,
      in normal people cognitive restraint has to be considered to be related to
      behavioral-cognitive factors rather than biologically driven by energy
      requirements.

PMID- 8286483
TI  - [Refractory ascites: a fifteen-year experience with the peritoneovenous shunt].
AB  - The authors consider the various causes of ascites and they also develop the
      concept of refractory ascites. They consider the various possibilities of medical
      and dietary therapy whose failure constitutes the basis for a surgical approach.
      In the latter case it is being considered the Peritoneo Venous Shunt (PVS) that
      employs different types of valves. In the light of their personal experience,
      matured over a period of 15 years, in which 75 valves were positioned in 64
      patients and precisely: 55 valves of Le Veen, 15 Hakim and 5 Denver, it is
      emphasized that the best results, as for as mortality and morbidity goes, were
      obtained through careful attention in the preoperative stage and during surgery
      itself with the privileged use of a Le Veen's valve. For such motives, since in a
      high percentage of these patients there persists a poor prognosis a year away
      from the onset of refractory ascites, a PVS seems proposable anyway and even
      though this will not alter the pathological outcome, there's a clear improvement
      in the quality of life without precluding any other surgical approach. Finally,
      the authors outline the possibilities offered by the Transjugular Intrahepatic
      Portosystemic Shunt (TIPS), as a new original approach for the resolution of
      refractory ascites.

PMID- 8286484
TI  - [Combined treatment of colorectal polyps with diathermy and the Nd-YAG laser. Our
      experience].
AB  - Among colorectal polyps, those of the sessile and villous type are said to bear a
      high frequency cancer degeneration. While surgery is considered the cure,
      alternative choices are to be offered in the presence of contraindications or
      lack of an informed consent. We analyzed the results of the "combined therapy"
      that requires the use of the ND-YAG laser following the ablation of the lesion
      with diathermic snare. We used an EV laser 132 with double wavelength to allow
      the ablation of flat lesions and minimize the risk of perforation. We included 12
      patients with sessile colorectal polyps. In 9/12 complete eradication was
      obtained over a follow-up 11 months; of the remaining 3, 2 dropped out, 1 did not
      respond. Owing to the small series, the relationship between the successful
      eradication and the size of the polyp cannot be evaluated. We conclude that the
      treatment of sessile colorectal polyps with this combined approach may be a
      promising one.

PMID- 8286485
TI  - [Pancreatic extract therapy in exocrine pancreatic insufficiency].
AB  - The authors consider the different strategies in long term enzyme replacement
      therapy in relation to the complex mechanics at the basis of pancreas exocrine
      insufficiency. This condition occurs in chronic pancreatitis and is present in
      Cystic Fibrosis, the most common potentially lethal inherited disorder of
      Caucasians. Pancreatic exocrine insufficiency occurs in the vast majority of
      cystic fibrosis affected children and is now becoming a frequent pathology in
      adults for the better life expectancy and the recent acknowledgements in this
      disease. The principal aims of research in enzyme replacement therapy have been
      directed at the formulation of products with high enzyme concentration, to the
      prevention of gastric acid inactivation of enzymes and to the better mixing of
      the preparations with meals. The authors consider all the different enzyme
      preparations from pancreatin powder to the 1st. generation of enteric coated
      tablets and examine the advantages of administering H-2 receptor antagonists or
      antacids and the possibility of stimulating bicarbonate secretion as an adjunct
      to pancreatic enzyme replacement therapy. Significant benefits in pancreatic
      insufficiency therapy have derived from the introduction of enteric coated
      microspheres which ensure a consistent level of enzymes to reach the duodenum
      mixed with the meal and which are resistant to gastric acid inactivation as well.

PMID- 8286486
TI  - [Clinical evaluation of calcium-polycarbophil in the treatment of non-specific
      diarrhea].
AB  - We performed a study on 10 patients aged between 26 and 54 males and females,
      affected by non-specific diarrhea. A single-blind clinical trial has been
      developed where Calcium-Polycarbophil was administered (2 cps t.i.d.) for a
      period of 8 weeks, half with placebo and half with drug in cross-over. No drop
      out occurred. Number of evaluations, cramps and consistency of stools, have been
      evaluated before and after treatment. A definite decrease of evacuations per day
      and of cramps, when present, together with a higher consistency of stools, are
      reported when Calcium-Polycarbophil is administered, according to the favourable
      medical judgement. Haematochemical parameters, evaluated before, during and after
      the treatment didn't show any relevant variation, apart from slight increase (not
      statistically significant) of calcium both in blood and in urine). No other
      unwanted event has been detected. Hence, the high therapeutic index of Calcium
      Polycarbophil makes it highly desirable in the treatment of diarrhea.

PMID- 8286487
TI  - Tertiary ambulatory care: its strategic importance in future health care.

PMID- 8286488
TI  - Educating the public--Norman Swan's Plagued.

PMID- 8286489
TI  - The definition and assessment of physical activity in cardiovascular risk
      reduction research.
AB  - Community-wide promotion of physical activity is becoming increasingly relevant
      in the development of social, economic, and health-related policy. Such research
      raises issues in the assessment of physical activity on a population basis. This
      paper reviews definitions of physical activity for cardiovascular risk reduction
      and the assessment techniques which arise from them, and makes some
      recommendations, firstly for the identification of appropriate levels of physical
      activity, and secondly for the development and selection of assessment
      techniques. It seems that a clearer conception of appropriate activity levels for
      fitness and for health will require further research with a range of population
      groups and activity types. Greater standardisation of questionnaires, improved
      validity of measures, and a greater understanding of possible response biases
      will also improve the quality of the basic information on which interventions and
      policies are developed.

PMID- 8286490
TI  - Comparison of three data collection methodologies for the study of young illicit
      drug users.
AB  - Three data collection methods (street-intercept, telephone ring-in and focus
      group discussions) were compared for their feasibility, reliability, validity and
      cost. The subjects of investigation were drug-related behaviours, attitudes and
      knowledge among current illicit drug users aged 16 to 21 years in Sydney. All
      three methods were found to be feasible and to produce reliable and valid
      information. Few differences in the demographic make-up and drug-use profiles of
      the samples were evident. The main differences between the data collections
      related to cost and the type of information obtained. The street-intercept method
      was the cheapest per completed interview and the focus-group method was the most
      expensive. Focus-group discussions were considered a valuable adjunct to the
      surveys because they facilitated an understanding of the quantitative survey
      results. It was concluded that the street-intercept method is the preferred
      survey method because of its lower cost and lower susceptibility to volunteer
      bias compared to the telephone ring-in. For repeated data collection to monitor
      changes in drug use patterns, street-intercept surveys in combination with focus
      group discussions are recommended.

PMID- 8286491
TI  - Sun-related attitudes and beliefs among Queensland school children: the role of
      gender and age.
AB  - A cross-sectional study of the sun-related attitudes and beliefs of 3,655
      children in Grades 7 to 11 attending 55 representative Queensland schools was
      undertaken using a structured questionnaire administered at school. Factors
      derived from a series of focus groups were incorporated into the questionnaire.
      Knowledge about risk factors in the aetiology of skin cancer and the role of
      protective measures was high. Several potential barriers to the use of sun
      protection were identified, including the desire to be tanned, the perceived
      attitudes of the peer group to sun protection, and difficulties with the use of
      specific sun protection measures. In general, these barriers were significantly
      more prominent among boys and children from older grades than other students.
      These data will be used to design school-based sun protection interventions which
      are sensitive to these age and sex differences.

PMID- 8286492
TI  - Solar protection behaviours: a study of beachgoers.
AB  - This study explored the prevalence and predictors of solar protection behaviour
      in a community sample of beachgoers. A total of 670 participants was randomly
      selected from six beaches in the Newcastle district. The solar protection
      behaviour of each participant was assessed by direct observation and interview. A
      subsample was also asked to complete a written questionnaire to assess attitudes
      to solar protection use, knowledge of skin cancer and awareness of recommended
      solar protection behaviours. Forty-five per cent of the beachgoers in this sample
      were using a high level of solar protection, and a substantial proportion (16 per
      cent) of the sample was not using any kind of solar protection. Sunscreen with
      SPF 15+ was applied to at least one body region by 69 per cent of the sample, 17
      per cent of the sample were wearing a recommended hat, 15.1 per cent were using
      shade, and 3.4 per cent were wearing a recommended style of shirt at the time of
      observation. Chi-square analyses of the data for under-15-year-olds indicated
      that a significantly greater proportion of 0- to 9-year-olds were well protected
      compared to 11- to 14-year-olds, but there was no difference in use of protection
      by boys and girls under 15 years of age. Stepwise regression analysis of the
      adult sample (15 years and over) showed that the predictors of overall level of
      solar protection were marital status and frequency of skin self-examination in
      the past 12 months. The practical implications of these findings for future
      community-based skin cancer prevention programs are discussed.

PMID- 8286493
TI  - The Good Heart, Good Life survey: self-reported cardiovascular disease risk
      factors, health knowledge and attitudes among Greek-Australians in Sydney.
AB  - This survey aimed to assess the prevalence and knowledge of coronary risk factors
      and self-perceived coronary heart disease risk among Greek-Australians in the
      Marrickville area of inner Sydney. A random sample of 834 household addresses was
      selected from the 2,403 households having Greek-Australian surnames on the
      electoral roll. In each household, one individual aged 18 years or over was
      selected using a Kish grid, and a questionnaire was administered by a bilingual
      interviewer. Questions concerned knowledge of and self-reported risk factors for
      coronary heart disease, and ratings of perceived stress, social support and
      networks. There was a response rate of 81 per cent of actual Greek-Australian
      households, a total of 541 interviews (61 per cent women). Most of the sample (86
      per cent) were born in Greece and 77 per cent of interviews were administered in
      Greek. The age-adjusted male prevalences of self-reported smoking, high blood
      pressure, high blood cholesterol and body mass index over 26 kg/m2 were 44 per
      cent, 5 per cent, 14 per cent and 58 per cent, respectively. The age-adjusted
      female prevalences of self-reported smoking, high blood pressure, high blood
      cholesterol and body mass index over 26 kg/m2 were 19 per cent, 8 per cent, 15
      per cent and 40 per cent, respectively. Compared to the National Heart Foundation
      risk-factor prevalence survey, the prevalence of self-reported high blood
      pressure was lower, but obesity and, among males, smoking, were higher. Low
      levels of education and poor English-language skills among older Greek
      Australians may be contributing to the problem.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286494
TI  - History of hepatitis B vaccination in New Zealand: lessons for Australia?
AB  - Recognition of the high prevalence of and the problems caused by the hepatitis B
      virus (HBV) infection in the North Island of New Zealand is largely due to the
      observations and work of one man, Alexander Milne. This article outlines the
      history of the events that led up to the culmination of his team's work--a
      national hepatitis vaccination strategy for New Zealand children. The situation
      in Australia is reassessed in the light of the New Zealand example with data
      based on benefit-cost analysis of various vaccination strategies.

PMID- 8286495
TI  - Assessing the extent of the Australian HIV epidemic from AIDS surveillance data.
AB  - Current knowledge about human immunodeficiency virus (HIV) disease is used to
      assess past and future trends in Australian HIV/AIDS (acquired immune deficiency
      syndrome) incidence, focusing on the precision with which such assessments can be
      made. The statistical method of back-projection is applied to reconstruct the
      past pattern of HIV incidence from surveillance data on AIDS incidence to June
      1992. The results indicate that HIV incidence rose rapidly in the early 1980s to
      peak in 1983-1984, followed by a sharp decline. This finding is insensitive to
      plausible variations from the assumptions made, and is consistent with both
      success in preventive strategies and high levels of infection in a subgroup
      having a high probability of exposure. Cumulative HIV incidence to the end of
      1987 is estimated with a 90 per cent confidence interval from 9,350 to 10,350.
      Estimation of the cumulative HIV incidence to June 1992 is less precise, with a
      90 per cent confidence interval of 12,900 to 17,800. After adjustment for
      underreporting the incidence could be as high as 22,000, but only if recent
      infection rates, which cannot be quantified accurately, were very high. Based on
      data to June 1992, the estimated trend in AIDS incidence indicates 680 new cases
      in 1993, rising gradually to 695 in 1995. The estimated rate of increase in AIDS
      incidence over the recent past and near future is significantly less than that
      observed earlier in the epidemic. This is a consequence of both the earlier peak
      in HIV incidence and the effect of therapy.

PMID- 8286496
TI  - Control of a community outbreak of measles which started in a poorly immunised
      high school population.
AB  - An outbreak of measles occurred in Darwin from February to March 1991. The first
      case was in a 13-year-old high school student who had returned from a holiday
      overseas. She was symptomatic on the second day of the new school term. She
      infected an infant while both waited in a doctor's surgery. Outbreak control
      measures were instituted 18 days later when the Communicable Diseases Centre was
      first alerted of cases through the laboratory notification scheme. Through active
      surveillance, we identified 76 cases of measles, of whom 92 per cent (70 cases)
      were under 20 years of age. Of these, 46 were students at the index high school
      in which the attack rate was 39.2 per 1,000. They transmitted the disease to six
      unvaccinated siblings aged 11 to 18 years, resulting in a secondary attack rate
      of 113 per 1,000 in this age group (relative risk of disease in siblings 2.8, 95
      per cent confidence interval 1.2 to 6.2). The outbreak affected one other high
      school, a number of primary schools, one tertiary institution, and nine children
      under five years. Only four of the cases had a verified history of previous
      immunisation against measles. The outbreak was arrested within two weeks of
      instituting community-wide control measures. Inadequate immunisation coverage
      among school-aged children and delays in notification contributed to the severity
      of the outbreak. Improved measles surveillance systems, including telephone
      notification of clinical cases are needed so that control measures can be
      instituted immediately within the household and in the community.

PMID- 8286497
TI  - A study of building structural features associated with high indoor air
      concentrations of organochlorine termiticides.
AB  - As part of a two-year study of post-treatment residential exposure to the
      termiticide, aldrin, the building structural features of ten houses with crawl
      space-type floors were assessed by an independent inspector. Building attributes
      recorded on a checklist included the age of the dwelling, room characteristics,
      floor details and the nature of subfloor ventilation. At the end of each
      inspection, the inspector, who was blinded to data on airborne aldrin
      concentrations, provided a rating of expected indoor air contamination. Several
      of the building attributes, including the age of the house, the area of exterior
      subfloor vents, as well as the inspector's rating, were significantly correlated
      with airborne aldrin values. No single building variable, however, was highly
      correlated with every measure of aldrin concentration over a 12-month period. The
      observed data are consistent with poor subfloor ventilation and a 'leaky' floor
      being important contributors to indoor air pollution. It is recommended that pest
      control companies advise householders about any obvious floor and ventilation
      deficiencies before soil treatment work is undertaken. Pesticide exposure (by
      analogy with geological radon exposure) may be reduced by sealing gaps in floors
      and/or by improving subfloor ventilation.

PMID- 8286498
TI  - An epidemiological study of falls in older community-dwelling women: the Randwick
      falls and fractures study.
AB  - Seven hundred and four women aged between 65 and 99 years (mean age 74.6 years),
      who were randomly selected from the community, took part in a study to determine
      whether health and lifestyle factors were associated with falls. In the 12 months
      before the survey, 66.1 per cent of the subjects experienced no falls, 19.7 per
      cent fell once and 14.2 per cent fell on two or more occasions. The proportion of
      women who fell outside the home decreased with age, with a corresponding increase
      in the proportion who fell inside the home on a level surface. The most common
      causes of falls reported were trips, slips and loss of balance. Some (27 per
      cent) suffered injuries as a result of a fall, and the proportion suffering
      injuries increased with age. Those who rated their health and balance as
      impaired, those with a limitation in activities of daily living, those receiving
      community services, those taking psychoactive drugs, and those taking four or
      more drugs had significantly more falls. On the other hand, those taking part in
      planned exercise and those active for seven or more hours per week had fewer
      falls. Smoking and alcohol consumption were not significantly associated with
      falls. Stepwise logistic regression analysis revealed poor vision, inactivity and
      subjective fall risk as variables that were independently and significantly
      associated with falling. These findings highlight possible intervention
      strategies for reducing falls risk in older people.

PMID- 8286499
TI  - Vitamin supplementation and nutritional status in homeless men.
AB  - Homeless men and women are both physically and socially disadvantaged. Their
      nutritional status is also often compromised. In this sample of 107 homeless men
      in Sydney, about half reported taking vitamin supplements (with varying duration
      and regularity), usually a regimen consisting of thiamin, vitamin C, folic acid
      and a multivitamin-B-complex capsule. In this cross-sectional study, little
      effect could be seen on clinical health between those reporting taking vitamin
      supplementation and those not doing so. However, biochemical measurements showed
      significant differences. The numbers of men classified as deficient were higher
      by about 20 per cent for those reporting not taking vitamins. The mean
      biochemical levels were significantly better for the supplemented group for
      thiamin, as assessed by TPP per cent effect (P = 0.04), vitamin B6, as assessed
      by P5'P per cent effect (P = 0.002), vitamin C (P < 0.001) and blood folate (P <
      0.02). Consequently, on the basis of mean biochemical levels of vitamin status,
      the supplemented group were better off and it is reasonable to presume that in
      the long term this would be reflected in improved clinical status.

PMID- 8286500
TI  - Inequalities in risk factors and cardiovascular mortality among Australia's
      immigrants.
AB  - Inequalities in biomedical and life-style risk factors for cardiovascular disease
      were examined for 6,116 immigrants to Australia and 14,941 people born in
      Australia, using data collected in the 1980, 1983 and 1989 risk-factor prevalence
      surveys. After adjusting for age and study design, significant differences were
      identified between immigrant groups and the Australian-born reference group,
      particularly for systolic blood pressure, overall obesity and behavioural risk
      factors. There were few substantial differences in blood lipid concentrations and
      little evidence to suggest that total plasma cholesterol has played a major role
      in lower cardiovascular mortality among immigrants. Overall, the results
      suggested that profiles of risk factors commonly accepted as determinants of
      cardiovascular disease are an insufficient explanation of the lower standardised
      mortality ratios from cardiovascular disease which characterise immigrants in
      Australia. Systolic blood pressure best explained variation in cardiovascular
      mortality among male immigrants, and smoking prevalence among female immigrants.
      The acculturation process affected immigrant groups differently. Generally,
      systolic blood pressure increased with period in Australia. Body mass index
      increased among Asian immigrants, as did participation in physical activity
      during leisure time.

PMID- 8286501
TI  - The health and wellbeing of informal caregivers: a review and study program.
AB  - Informal caregivers are the families and other unpaid caregivers in the home who
      support people of all ages with severe and chronic mental or physical
      disabilities. Home care of this sort has been increasing over the past 30 years
      because of the reduced number of beds in hospitals and nursing homes and
      increased outpatient and community care. Moreover, with an aging population and
      increasing rates of disability, the demand for family caregiving will continue to
      rise. This has important implications for the development of health, community
      service and social policy. At the same time, however, very little is known about
      the impact such changes are having on the caregivers of various ages and in
      various circumstances. The Victorian Health Promotion Foundation is funding a
      research and intervention program in Melbourne to promote wellbeing and prevent
      ill-health in caregivers.

PMID- 8286502
TI  - Perceptions of unmet need in four community services for elderly people.
AB  - Home-care services particularly, and food services to a lesser extent, are seen
      by elderly people as being critically important for their capacity to live
      independently in western Sydney. Home nursing and transport services are valued
      but are less critical. Consumers, providers of services and referral agents all
      identify significant levels of unmet need for community services. The home care
      service particularly is stretched by pressures which are likely to be exacerbated
      by demographic change and by cost-shifting between state governments and the
      Commonwealth Governments.

PMID- 8286503
TI  - Injuries due to falls from horses.
AB  - This study describes the epidemiology of injuries due to falls from horses in New
      Zealand. There were 54 fatalities from 1977 to 1986 (0.17 per 100,000 persons per
      year). There were 773 hospitalisations in 1987 (23.7 per 100,000 persons per
      year). Head injuries were predominant among both fatal and nonfatal injuries. The
      incidence of nonfatal head injury in the 10 to 19 age group was significantly
      higher than the incidence in all older groups (P = 0.003). Young people,
      particularly females, were the segment of the population most affected by the
      problem of falls from horses. Reference to data on horse-riding participation
      rates, however, did not indicate that young people were overrepresented in the
      series studied. Reference to the same data showed that the rate of
      hospitalisation due to falls from horses is comparable to the rate for injuries
      from playing rugby. The magnitude and severity of the problem indicates that
      there is a need need for helmet use, safe-riding practices, and further research.

PMID- 8286504
TI  - Quality-adjusted life years: origins, measurements, applications, objections.
AB  - Quality-adjusted life years or QALYs are used to combine, in a single measure,
      information about the quantity and quality of life produced by a health
      intervention. They have been used as outcome measures in clinical trials and in
      cost-effectiveness analyses. This paper describes how QALYs are assessed and how
      they are used. Methodological and theoretical problems are discussed as are
      ethical objections to the utilitarian ethos underlying their use. It is concluded
      that QALYs are part of a technology that is still in development but, because of
      the lack of alternatives, they will certainly continue to be used. It is
      important to resolve the outstanding methodological issues and reach an ethical
      consensus to ensure that QALYs truly reflect community goals.

PMID- 8286505
TI  - QALYs for resource allocation: probably not and certainly not now.
AB  - Quality-adjusted life years (QALYs) have the attractive characteristic of
      combining morbidity and mortality into a single index which purports to measure
      the outcomes of health interventions. Their primary aim, when combined with cost,
      is to permit comparisons across candidate spending programs and thereby promote
      economic efficiency in the use of rationed funds. QALYs, in fact, comprise a
      family of measures with major differences in approach and many variations in
      construction, process and methods of measurement. A necessary unifying
      characteristic is the ethical assumption of utilitarianism. The paper examines
      the state of the art in the development of QALY measures. It concludes that they
      fall far short of requirements for their advocated use in resource allocation
      decisions. Furthermore, their demands on measurement for this purpose are such
      that it is unlikely that methodological problems can be solved.

PMID- 8286506
TI  - Chemical hazards in the Melbourne metropolitan area.

PMID- 8286507
TI  - Cadaverous particles and infection in injured man. Clinical review based on the
      Semmelweis Lecture.

PMID- 8286508
TI  - Effect of povidone-iodine lavage on peritoneal defence mechanisms in rats.
AB  - OBJECTIVE: To assess the effect of povidone iodine lavage on peritoneal defence
      mechanisms in rats. DESIGN: Randomised study. MATERIAL: 90 Wistar albino rats.
      INTERVENTION: Rats were divided in three groups of 30. All rats underwent midline
      laparotomy, and 20 rats in each group had peritoneal lavage with 20 ml 1%
      povidone iodine, samples being taken before lavage in 10 and after lavage in 10.
      MAIN OUTCOME MEASURES: Effect of povidone-iodine lavage compared with laparotomy
      alone on bactericidal activity of peritoneal fluid (group 1); chemotactic indices
      of polymorphonuclear leucocytes (PMNL) (group 2); and total cell counts, cell
      types, and peritoneal phagocytic activity (group 3). RESULTS: Lavage with
      povidone-iodine increased the total peritoneal cell count/washing from 10.4 x
      10(6) to 12.4 x 10(6) (p < 0.005), peritoneal bactericidal activity from 69.2% to
      92.7% (p < 0.05), and peritoneal phagocytic activity from 58.9% to 73.7% (p <
      0.05) at the end of four hours. Chemotactic indices of peritoneal PMNL before and
      after lavage were 1.90 and 1.89, respectively. Among the cells in the peritoneal
      fluid, the proportion of PMNL increased, whereas those of macrophages,
      lymphocytes, and mast cells decreased (p < 0.005). CONCLUSIONS: These results
      differ from those that we found previously after saline lavage. Lavage with 1%
      povidone-iodine does not increase the detrimental effect of saline lavage; on the
      contrary, it may even enhance peritoneal defence mechanisms. Any detrimental
      effects of povidone-iodine lavage should be attributed to systemic rather than
      local toxicity.

PMID- 8286509
TI  - Perioperative TNF alpha and IL-6 concentrations correlate with septic state,
      organ function, and APACHE II scores in intra-abdominal infection.
AB  - OBJECTIVE: To find out if concentrations of tumour necrosis factor a (TNF alpha)
      and interleukin-6 (IL-6) play a part in the pathophysiology of intra-abdominal
      infection, and try to identify patients who would benefit from immunotherapy
      against TNF alpha. DESIGN: Prospective open study. SETTING: University hospital.
      SUBJECTS: 19 consecutive patients (septic shock, n = 4; sepsis syndrome, n = 6;
      and no sepsis syndrome, n = 9, classified by the APACHE II score and the criteria
      of the Methyl-prednisolone Severe Sepsis Study Group) who were to undergo their
      first operation for intra-abdominal infection. MAIN OUTCOME MEASURES: Correlation
      between median (interquartile) concentrations of TNF alpha and IL-6 (pg/ml), and
      APACHE II score, plasma lactate concentration, and organ function. RESULTS:
      Perioperative concentrations of both TNF alpha (p = 0.001) and IL-6 (p = 0.006)
      were significantly higher in patients with septic shock. Preoperative
      cardiovascular and respiratory failure were associated with significantly raised
      TNF alpha (p < 0.001 in both cases) and IL-6 concentrations (p = 0.02 and p <
      0.001, respectively). The preoperative APACHE II score correlated with the
      increased TNF alpha concentration (r = 0.5, p < 0.001) and plasma lactate
      concentration with that of IL-6 (r = 0.7, p = 0.003). CONCLUSION: Perioperative
      TNF alpha and IL-6 concentrations correlated with the severity of intra-abdominal
      infection, so it is possible that patients who present with either septic shock
      or the sepsis syndrome may benefit from immunotherapy against TNF alpha.

PMID- 8286510
TI  - Multivariate analysis for predicting the presence of bacteria in bile in patients
      with acute cholecystitis.
AB  - OBJECTIVE: to find out whether the presence of bacteria in bile could be
      predicted accurately from preoperative data in patients with acute cholecystitis.
      DESIGN: Prospective open study. SETTING: University hospital. SUBJECTS: 42
      patients undergoing cholecystectomy for acute gallstone cholecystitis. MAIN
      OUTCOME MEASURES: Correlations between 24 preoperative clinical and laboratory
      variables, and the incidence of pathogenic organism in bile. RESULTS: 4 of the 24
      variables tested were of predictive significance. These were external body
      temperature on admission, percentage of neutrophils, preoperative white blood
      cell count, and total serum concentration of bilirubin. When these predictive
      variables were evaluated in the discriminant analysis equation they had a
      sensitivity of 92% and a specificity of 100% in predicting positive bile culture.
      CONCLUSION: Multivariate discriminant analysis permits accurate preoperative
      prediction of bile cultures growing pathogens in patient undergoing
      cholecystectomy for acute cholecystitis.

PMID- 8286511
TI  - Effect of sepsis-related cytokines on lipid synthesis by isolated human
      hepatocytes.
AB  - OBJECTIVE: To investigate the effect of tumour necrosis factor-alpha (TNF-alpha)
      and other sepsis related cytokines on the synthesis of several lipid fractions by
      human hepatocytes. DESIGN: Laboratory study. SETTING: University departments of
      surgery and biochemistry. MATERIAL: Livers from eight donors of other organs.
      MAIN OUTCOME MEASURES: Effect of TNF-alpha, interleukin-1 (IL-1), and interleukin
      6 (IL-6) on the synthesis of triacylglycerol and phospholipids by freshly
      isolated human hepatocytes. RESULTS: All three cytokines, particularly TNF-alpha,
      inhibited the incorporation of D-glucose uniformly labelled with 14C (D-(U-14C)
      glucose) into phosphatidylcholine. The incorporation of D-(U-14C) glucose into
      triacylglycerol and free fatty acids was significantly stimulated by TNF-alpha
      and IL-1, but not by IL-6. When palmitate uniformly labelled with 14C was used as
      the radiolabelled precursor, TNF-alpha stimulated the synthesis of both
      triacylglycerol and phosphatidylcholine, neither of which was affected by IL-1 or
      IL-6. CONCLUSION: Changes that are induced by cytokines in lipid synthesis by
      hepatocytes can contribute to the impairment of lipid metabolism seen in septic
      patients. TNF-alpha seemed to have more effect than the other two cytokines.

PMID- 8286512
TI  - Tumour necrosis factor-alpha inhibits synthesis of surfactant by isolated human
      type II pneumocytes.
AB  - OBJECTIVE: To investigate the effect of tumour necrosis factor-alpha (TNF-alpha)
      on the synthesis of surfactant by human type II pneumocytes. DESIGN: Laboratory
      study. SETTING: University departments of surgery and biochemistry. MATERIAL:
      Segments of right lower lobe of lungs from nine donors of other organs, and from
      tumour-free portions of 10 lungs excised from patients with lung cancer. MAIN
      OUTCOME MEASURES: Effect of TNF-alpha on the incorporation of D-glucose and
      palmitate, both of which had been uniformly labelled with 14C (D-(U-14C) glucose
      and (U-14C) palmitate), into various phospholipid fractions by pneumocytes
      isolated from both healthy lungs and those from patients with lung cancer.
      RESULTS: TNF-alpha decreased the incorporation of both D-(U-14C) glucose and (U
      14C) palmitate into phospholipid fractions, particularly phosphatidylcholine, in
      both healthy lung tissue and that from patients with lung cancer. The degree of
      inhibition was less in the group from patients with lung cancer because the basal
      value was lower. CONCLUSION: TNF-alpha may contribute to the pathophysiology of
      the adult respiratory distress syndrome by inhibiting the synthesis of
      surfactant. The results suggest the possibility that TNF-alpha may be produced
      locally in the presence of lung cancer resulting in chronic paracrine or systemic
      exposure of pneumocytes to low concentrations of the cytokine.

PMID- 8286513
TI  - Restoration of bactericidal activity of peritoneal fluid by cimetidine but not
      ranitidine or famotidine in burned mice.
AB  - OBJECTIVE: To find out the effect of 20%, third degree burns and H2 receptor
      antagonists on peritoneal bactericidal activity. DESIGN: Animal experiment.
      SETTING: Research laboratory of university school of medicine. SUBJECTS: 52 mice
      in five groups. INTERVENTIONS: Sham burn (n = 5, group I), burned, and received
      subcutaneous injections of saline (0.3 ml/kg day, n = 14, group II); ranitidine
      (10 ml/kg/day, n = 15, group III); cimetidine (10 mg/kg/day, n = 8, group IV); or
      famotidine (0.7 mg/kg/day, n = 10, group V); for 14 days. MAIN OUTCOME MEASURE:
      Peritoneal bactericidal activity in all groups measured 15 days after the burn.
      RESULTS: There was a significant difference in peritoneal bactericidal activity
      between the control and burned mice, but no significant difference between the
      control group and the burned mice that were given cimetidine and famotidine.
      CONCLUSION: Peritoneal bactericidal activity is suppressed in mice after 20%
      third degree burns and this effect may be partly reversed by cimetidine and
      famotidine.

PMID- 8286514
TI  - Outcome at three to five years of primary closure of perianal and pilonidal
      abscess. A randomised, double-blind clinical trial with a complete three-year
      followup of one compared with four days' treatment with ampicillin and
      metronidazole.
AB  - OBJECTIVE: To evaluate the long term results after primary closure of perianal
      abscess and pilonidal sinus. DESIGN: Follow up by questionnaire and study of
      casenotes. SETTING: University hospital and district hospital. SUBJECTS: 88
      Patients who had previously been in a prospective random control trial of two
      regimens of antibiotic treatment (ampicillin and metronidazole for one compared
      with four days) before incision, curettage, and primary closure of perianal
      abscess or pilonidal sinus. MAIN OUTCOME MEASURES: Recurrence rate and outcome.
      RESULTS: 32 Patients had perianal abscesses of which 31 (97%) healed primarily
      (95% confidence interval [CI] 84 to 100%) with 4 recurrences (13%, 95% CI 2 to
      24%). 56 Patients had pilonidal sinuses or abscesses of which 46 (82%) healed
      primarily (95% CI 70 to 91%) with 14 recurrences (30%, 95% CI 16 to 40%). There
      were no significant differences between the two antibiotic regimens. The mean
      followup was 53 months. Two patients had died, both had had perianal abscesses.
      Pilonidal sinuses tended to recur during the first year, whereas pilonidal
      abscesses recurred after a lapse of two years or more. Half the patients who had
      had previous operations for the same complications, compared with a third who
      were being operated on for the first time. CONCLUSIONS: A one day course of
      ampicillin and metronidazole is not associated with any more complications than a
      four day course. Perianal abscesses respond well to primary closure, but
      management of pilonidal abscesses and sinuses is more difficult.

PMID- 8286515
TI  - Comparison of HA-1A and E5 monoclonal antibodies to endotoxin in rats with
      endotoxaemia.
AB  - OBJECTIVE: To investigate the ability of two anti-endotoxin IgM antibodies (10
      mg/kg) to prevent the hyperdynamic response induced by infusion of Escherichia
      coli rough mutant endotoxin core types R1 and R2 in rats. DESIGN: Randomised
      blind laboratory study. SETTING: University department of surgery. MATERIAL: 8
      groups of 5 male Sprague-Dawley rats and 10 control animals. MAIN OUTCOME
      MEASURE: Percentage change in cardiac output during the period of observation.
      RESULTS: E5 provided significant protection against R1 (p = 0.04) but not against
      R2. HA-1A gave significant protection against R2 (p < 0.04) but not against R1.
      In clinical isolates of E. coli the R1 type predominates (about 70%). CONCLUSION:
      These results may reflect true differences in specificity between the antibodies,
      but there remains the possibility that these are non-specific effects. Further
      controls with irrelevant murine and humanized IgM monoclonal antibodies are in
      progress.

PMID- 8286516
TI  - Fish oil increases the release of tumour necrosis factor and interleukin-6, and
      has no effect on the incidence of multiple organ failure in rats with
      peritonitis.
AB  - OBJECTIVE: To find out if fish oil given intraperitoneally would cause a
      reduction in the release of tumour necrosis factor and interleukin-6 in abdominal
      exudate and blood (experiment A), and if it reduces the incidence of organ
      failure in rats with peritonitis (experiment B). DESIGN: Laboratory experiment.
      SETTING: University animal laboratory. MATERIAL: Thirty-six selectively
      decontaminated rats in each experiment. INTERVENTIONS: All rats were pretreated
      with 2 ml fish oil, lecithin, or saline, intraperitoneally for one or six weeks
      before intraperitoneal injection of zymosan. Experiment A: Samples of abdominal
      exudate and plasma were taken regularly for 24 hours after the zymosan had been
      given. Experiment B: Clinical, biochemical, and histological variables were
      measured over a 12-day period after the zymosan had been given. MAIN OUTCOME
      MEASURES: Experiment A: Concentrations of tumour necrosis factor and interleukin
      6 in abdominal exudate and plasma. Experiment B: Incidence of multiple organ
      failure. RESULTS: Experiment A: Concentrations of tumour necrosis factor and
      interleukin-6 in abdominal exudate and plasma were significantly higher in rats
      pretreated with fish oil, compared with control rats. This effect was more
      pronounced after six weeks of pretreatment. Experiment B: There were no
      significant differences between the groups for any variable. CONCLUSION: Fish oil
      given intraperitoneally increased rather than reduced local and systemic release
      of tumour necrosis factor and interleukin-6, and did not reduce the incidence of
      organ failure in rats with sterile peritonitis.

PMID- 8286517
TI  - Outcome of intra-abdominal infection in pigs depends more on host responses than
      on microbiology.
AB  - OBJECTIVE: To assess the effects of mortality of the presence and proliferation
      of bacteria, and the host's response to infection, in pigs with peritonitis.
      DESIGN: Laboratory study. SETTING: University hospital. MATERIAL: 71 Swedish
      Landrace pigs, 63 with peritonitis and 8 without (controls). INTERVENTIONS:
      Induction of peritonitis by intraperitoneal infusion of equal amounts of
      Escherichia coli and Bacteroides fragilis (10(9) to 10(11) bacteria/animal);
      sterile faeces were added in half the experiments. MAIN OUTCOME MEASURES:
      Microbiological events were quantified as the area under the bacterial
      concentration curve from 0-6 hours. Host responses were quantified with a score
      of 8 physiological variables measured between 4-6 hours after the induction of
      peritonitis. RESULTS: Of the 63 infected animals, 37 (59%) died within 6-24 hours
      and both the physiological response and the bacterial load were significantly
      higher in those that died. Logistic regression analysis with death as the
      dependent variable showed that the physiology score carried more predictive
      information than the quantification of bacterial load. CONCLUSION: The
      quantification of local events within the abdomen is of only limited predictive
      value compared with the extent of the physiological alterations.

PMID- 8286518
TI  - The influence of splenectomy on infective morbidity after colonic and splenic
      injuries.
AB  - OBJECTIVE: To establish the incidence of early postoperative infections after
      civilian injuries to the spleen, colon, or both and assess the effect of
      splenectomy on outcome. DESIGN: Retrospective study of case notes. SETTING:
      University hospital. SUBJECTS: 403 Patients of whom 353 had splenic injuries, 91
      with associated colonic injuries, together with 50 randomly selected patients
      with colonic injuries alone. MAIN OUTCOME MEASURES: Morbidity and mortality.
      RESULTS: 45 Patients had splenectomy and colonic injury (group 1), 46 had a
      colonic injury and the spleen conserved (group 2) 50 had colonic injury alone
      (group 3), 143 had splenectomy for injured spleen without colonic injury (group
      4), and 119 had the spleen injured and conserved without colonic injury (group
      5). Their mean age was 28 years. Overall mean Injury Severity Score (ISS) was
      30.1, and Abdominal Trauma Index (ATI) 22.4. 68/403 died (17%), more than half
      within 48 hours. Early mortality was higher in both groups in which the spleen
      was removed but after stratification by ISS and ATI the differences were not
      significant. Late mortality (after 48 hours) associated with sepsis did not
      differ significantly among the groups, nor did the rate of infective
      complications. Mechanism and severity of injury had the most influence on
      morbidity and mortality. CONCLUSION: Removal of an injured spleen does not have
      an adverse influence on the incidence of serious infective complications in the
      early postoperative period in patients with injuries to the spleen, the colon, or
      both.

PMID- 8286519
TI  - Age-related morphological changes in the testis of the BDF1 mouse.
AB  - Age-related morphological changes in the testis of the BDF1 mouse were studied by
      light and transmission electron microscopy. No apparent changes were detected
      until 12 months of age. After 18 months of age, vacuoles firstly appeared in the
      seminiferous epithelium. These vacuoles were gradually increased in number and
      showed a tendency to cluster with each other in accordance with age. While, germ
      cells were decreased in number. The sloughing of germ cells caused a thin
      seminiferous epithelium. In the tubule with a thin epithelium, spermatogenesis
      was severely interrupted. After 30 months of age, extremely thin seminiferous
      epithelia were observed. In these epithelia, most of spermatids and spermatocytes
      disappeared, and most of Sertoli cells lost their polarity to be flattened. On
      the other hand, in the interstitial region, PAS-positive cells (mononuclear
      phagocytes) tended to increase in number after 24 months of age. PAS-positive
      extracellular matrix newly appeared at 27 months of age. In the cytoplasm of
      Leydig cells, a whorl of sER was frequently found. Degeneration of testes
      proceeded with age. The regressive tubules occupied only 2.2% at 18 months of
      age, but extended to 63.0% at 33 months.

PMID- 8286520
TI  - Passive protection of mice against Actinobacillus pleuropneumoniae infection by
      monoclonal antibodies.
AB  - Mouse monoclonal antibodies (MAbs), Y-4b, F-6b and K-6a recognized as capsular
      antigens of A. pleuropneumoniae serotypes 1, 2 and 5, respectively, and MAb H-1b
      as lipopolysaccharide (LPS) of serotype 2 were produced. We examined the passive
      immunizing efficacy of these MAbs on A. pleuropneumoniae infection in C3H/HeJ
      mice. On the challenge infection of homologous serotype strains, they showed a
      sufficient protective effect in immunized mice. It was concluded that MAbs
      recognized as capsular antigen and LPS have a serotype-specific protective effect
      on A. pleuropneumoniae infection, suggesting the important role in preventing A.
      pleuropneumoniae infection.

PMID- 8286521
TI  - Sedative effect induced by a combination of medetomidine and midazolam in pigs.
AB  - Sedative and analgesic/anesthetic effects induced by a combination of
      medetomidine and midazolam were evaluated in pigs. This combination exerted a
      much more potent sedative effect than that induced by a medetomidine alone, even
      if the dose of medetomidine was reduced to one half, and even if the pigs were
      stimulated continuously during the induction phase. Pigs given this combination
      were induced to sedation smoothly and very quickly. During being sedated the
      arousal reaction induced by sensory stimuli were depressed profoundly and pigs
      could be placed in dorsal recumbency without any resistance. In addition, this
      combination produced moderate analgesic effect and apparent muscle relaxation.
      This potent effect induced by this combination seemed to be induced by a
      synergistic interaction between medetomidine and midazolam because the sedative
      effect achieved with this combination was much greater than that which could be
      expected from a simple additive response of both sedatives. This sedative
      combination may be a widely available and valuable for chemical restraint in
      pigs.

PMID- 8286522
TI  - Peritoneal dialysis using a recycling system in dogs.
AB  - In this study, Recirculation Peritoneal Dialysis (RPD) apparatus using a pump to
      circulate the dialysate was devised and its dialysis efficiency was investigated.
      In the experiment, 15 mongrel dogs with body weights of 6.6 +/- 0.7 kg were used.
      The surgery to induce azotemia was performed on the dogs, a disk catheter for
      drainage was placed between the liver and diaphragm, and a straight catheter for
      infusion was placed on the abdominal side of the bladder. RPD was conducted using
      2 l of dialysate containing 1.3% glucose, and the dialysate was circulated by a
      pump through the peritoneal cavity and the dialysate chamber at the circulation
      rates of 30, 60, 90 and 120 ml/min. RPD was conducted for 3 hr and the clearances
      of urea nitrogen, creatinine, inorganic phosphorus and potassium were recorded
      every hour. The clearances in RPD became higher with an increase in the
      circulation rate. Although RPD requires two catheters in the peritoneal cavity,
      it has no appreciable technical difficulty in handling and is considered to be
      easier than hemodialysis. RPD enabled higher dialysis efficiency to be achieved
      in a short time compared with conventional peritoneal dialysis. It seems
      reasonable to conclude that RPD is a useful new dialysis technique for animals.

PMID- 8286523
TI  - Swine interleukin 2 activity produced by mesenteric lymph node cells.
AB  - Swine interleukin 2 (IL-2) activity was assayed by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay using murine IL-2
      dependent cell line (CTLL-2). The culture supernatant of mesenteric lymph node
      (MLN) cells stimulated with phytohemagglutinin-P (PHA) induced a generation of
      MTT formazan in a dose-dependent manner, suggesting dose-dependent proliferation
      of CTLL-2. The maximal swine IL-2 activity was observed in the culture of MLN
      cells at 1 to 2 x 10(7) cells/ml when stimulated with 20 to 40 micrograms/ml PHA
      for 48 hr. Based on these findings, a large culture of MLN cells to prepare swine
      IL-2 were performed under the following condition; cell concentration of 1 x
      10(7) cells/ml, PHA concentration of 20 micrograms/ml, a culture scale of 200 to
      400 ml, and a stirring speed of 30 rpm. Swine IL-2 activity was detected from 4
      hr after PHA stimulation, and rapidly increased until 16 hr. Almost maximal IL-2
      activity in stirring culture was observed at the incubation of 20 hr. Swine IL-2
      was partially purified by Sephacryl S-200 gel filtration and the estimated
      molecular weight was about 32 kD based on the peak of IL-2 activity. The pI value
      of swine IL-2 was estimated to be approximately pH 5.3. Swine IL-2 was sensitive
      to acid (pH 3.2) or alkaline (pH 10.5), 4 or 8 M urea, trypsin, and the heating
      at 70 degrees C. These physico-chemical properties of swine IL-2 was similar to
      those of human, murine or feline IL-2.

PMID- 8286524
TI  - Dot-blot hybridization using digoxigenin-labeled cDNA probe complementary to the
      S1 gene of avian infectious bronchitis virus permits discrimination between virus
      strains.
AB  - Digoxigenin-dUTP-labeled DNA probe was prepared from a cDNA clone complementary
      to the gene encoding S1 region of the spike protein of infectious bronchitis
      coronavirus (IBV) strain M41. The probe exclusively reacted with four strains at
      56 degrees C which were grouped to the same serotype as the strain used for the
      probe. In contrast, at 68 degrees C, the probe reacted only with the homologous
      strain and did not react even with the strains belonging to the same serotype.
      The dot-blot hybridization thus appeared serotype-specific at 56 degrees C and
      strain-specific at 68 degrees C. In addition, it was revealed that the S1 gene
      has some nucleotide sequence variation even among strains in the same serotype.
      This technique should be applied to determining serotypes of the virus isolates
      and to differentiating field isolates from the vaccine strain.

PMID- 8286525
TI  - Application of polymeric N-acetyl-D-glucosamine (chitin) to veterinary practice.
AB  - The sponge-, cotton-, and flake-type remedies made of chitin (chitin-sponge,
      chitin-cotton, and chitin-flake, respectively), and non-woven fabric of polyester
      (NWF) composited with chitin (chitin-NWF) were applied to various types of
      trauma, abscess, surgical tissue defect and herniorrhaphy in 147 clinical cases
      including 72 dogs, 38 cows, 33 cats, 2 rabbits, one monkey and one horse. Chitin
      sponge was applied in 30 cases as filling agent of surgical tissue defect, and in
      25 cases of trauma, 31 cases of abscess as wound dressing or tissue defect
      filling agent. In 77 out of 86 cases (89.5%), good healing developed. When chitin
      sponge was buried in surgical tissue defects due to oncotomy in 20 cases,
      recurrence of the tumor developed in one case on one month post-operatively, but
      was not recognized for 3-24 months in 19 cases. Chitin-NWF was applied in 2 cases
      of trauma and 12 cases of abscess as wound dressing or tissue defect filling
      agent, 6 cases as filling agent of surgical tissue defect, and 12 cases of
      umbilical hernia as prosthesis of suture site of hernia ring. In 28 out of 32
      cases (87.5%), good healing developed. Chitin-cotton was applied in 8 cases of
      trauma and 12 cases of abscess as wound dressing or tissue defect filling agent.
      In 18 out of 20 cases (90.0%), good healing developed. Chitin-flake was applied
      in 9 cases of trauma as wound dressing or tissue defect filling agent. In 8 out
      of 9 cases (88.9%), good healing developed. In all cases, no side effects were
      observed.

PMID- 8286527
TI  - Chronic Sarcocystis infections in slaughtered cattle.
AB  - Parasitological, histopathological and immunohistochemical examinations were
      carried out on three slaughtered cattle with many nodules in all the striated
      muscles. At necropsy, many yellowish green rice-grain sized nodules including
      cheesy contents were observed in all the striated muscles. Histopathologically
      the nodules were granuloma principally consisting of eosinophiles. No Sarcocystis
      cysts nor bradyzoites were found in the nodules, but intact sarcocysts were found
      in the normal tissues surrounding the nodules. The central necrotic focus of
      nodules showed intense positive responses against anti-Sarcocystis cruzi rabbit
      serum by immunohistochemical examination. From the above findings the slaughtered
      cattle were diagnosed as chronic sarcocystiasis.

PMID- 8286526
TI  - Two-step polymerase chain reaction for diagnosis of scrub typhus and
      identification of antigenic variants of Rickettsia tsutsugamushi.
AB  - Two-step polymerase chain reaction (nested PCR) method was examined for the
      diagnosis of scrub typhus. Primers were derived from the type-specific antigen
      (TSA) gene DNA sequences of Rickettsia tsutsugamushi, Gilliam strain. These
      primers served to produce rickettsia-specific products in the amplification of
      template DNA prepared from all serovariants, Gilliam, Karp, Kato, Kawasaki,
      Kuroki and Shimokoshi strains, and the fragments of product after digestion with
      several kinds of restriction endonuclease showed the respective patterns to
      strain in acrylamide or agarose gel electrophoresis. The rickettsia-specific DNAs
      were also derived, by this nested PCR, by amplifying DNA from patients' bloods
      and mites from endemic areas, and the serotype of rickettsiae infected to these
      hosts could be identified from fragment patterns of the amplified products
      observed after endonuclease treatment. These results indicate that this PCR is
      sensitive and specific method not only for detection of rickettsial DNA in
      patient specimens and in mites, but also for the typing of rickettsiae infected
      to these hosts.

PMID- 8286528
TI  - Effects of milbemycin D on microfilarial number and reproduction of Dirofilaria
      immitis in dogs.
AB  - A single dose (1 mg/kg) of milbemycin D was administered orally to 24 dogs with
      microfilaremia of Dirofilaria immitis, and the number of circulating
      microfilariae was counted weekly. The number was decreased by 3 to 8% of the
      pretreatment levels 1 week after the drug administration. The number remained
      relatively stable for the first 8 weeks and was gradually increased thereafter
      without returning to the pretreatment levels by 20 weeks. Three or 4 dogs each
      were euthanatized on day 1, and 1, 4, 8, 12, 16 and 20 weeks after the drug
      administration to examine the effects of the drug on intrauterine microfilariae
      and embryos of the worms. Although no intrauterine microfilariae were destroyed
      directly by the drug, degeneration and collapse of morular embryos and decrease
      in the number of intrauterine microfilariae were observed 12 after weeks the drug
      administration. These findings became more remarkable with time, and no
      intrauterine microfilariae developed in any worms by 20 weeks. The electron
      microscopic findings revealed that the nucleoli of oocytes had a high density in
      the worms of 1, 4 and 8 week groups. Unequal size of cleavage cells and decrease
      of polysome number were noticed in the early-stage embryos after 8 weeks. It was
      assumed that the drug might have some effect on the chromosomes or genes in the
      germinal stem-cell of the heartworm and interfere with protein syntheses,
      resulting in inhibition of embryonic development. Twelve dogs were given
      milbemycin D (1 mg/kg) a total of 4 or 6 times monthly according to a
      prophylactic program.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286529
TI  - Detection of bovine coronavirus by enzyme-linked immunosorbent assay using
      monoclonal antibodies.
AB  - A sensitive and highly specific enzyme-linked immunosorbent assay (ELISA) system
      for detection of bovine coronavirus was developed using monoclonal antibodies,
      which showed both neutralization and hemagglutination inhibition activities. A
      monoclonal antibody was coated onto microplates for capturing antigen and a
      mixture of two monoclonal antibodies served as detecting antibodies. Using this
      assay, 40 of 202 fecal specimens from 29 herds were shown to be positive for
      viral antigen. From 10 ELISA positive specimens from 5 herds, the virus was
      isolated after several passages on human rectal adenocarcinoma (HRT-18) cell
      culture.

PMID- 8286530
TI  - Rearrangements of immunoglobulin and T-cell receptor genes in canine
      lymphoma/leukemia cells.
AB  - Tumor cells from 15 canine lymphoma/leukemia cases were examined for genetic
      rearrangements of immunoglobulin and T-cell receptor (TCR) genes in parallel with
      cell surface antigens. Ten of these 15 cases showed rearrangements of the
      immunoglobulin heavy chain (IgH) gene, while 4 cases displayed TCR beta-chain
      gene rearrangements on Southern blot analysis. All the cases with IgH gene
      rearrangements had multicentric form lymphoma, and 6 of the 10 cases were cell
      surface immunoglobulin-positive. On the other hand, the cases with TCR gene
      rearrangements included atypical lymphoma/leukemia cases, and 3 of the 4 cases
      were Thy-1 antigen-positive. Although the tumor cell lineage of a considerable
      number of lymphoma/leukemia cases could not be determined by phenotypic analysis,
      examination of the IgH and TCR gene rearrangements disclosed the lineages of 14
      of 15 cases. Genetic analysis demonstrated that the tumor cells in most canine
      multicentric lymphomas were formed by clonal expansion of B-lymphocyte. These
      findings show that studies on the rearrangements of immunoglobulin and TCR genes
      are very useful for understanding the cellular origin, clonality and hierarchy of
      canine lymphoma/leukemia cells.

PMID- 8286531
TI  - A retrospective study of ventral fenestration for disk diseases in dogs.
AB  - Sixty-six dogs suffering from intervertebral disk diseases on cervical and/or
      thoracolumbar disks were treated by a ventral fenestration. The breeds affected
      with disk diseases were Dachshund (65.1%), Beagle (15.2%), Shih Tsu (4.5%),
      Pekingese (4.5%), and others (18.2%). Sites suffered from disk diseases and
      received disk fenestration most frequently were from T10-11 to L2-3. However,
      other disks were also needed the operation in some cases. An average number of
      disks received fenestration was 6.0. Days to walk after the fenestration in 51
      cases varied 1 to 120 days (average: 14.9 +/- 22.0 days, mean +/- S.D.) depending
      on their severity. The recovery rates from the follow-up study were as follows:
      In grade I (3 cases, able to walk with back pain) and grade II (14 cases, slight
      ataxia and paresis) it was 100%, respectively. The rates in grade III (23 cases,
      paraplegia with positive deep pain) and grade IV (26 cases, paraplegia with lack
      of deep pain) were 73.9% and 65.4%, respectively. A few recurrence after the
      operation were observed in this study. As a result, the ventral fenestration was
      extremely effective as a treatment for disk diseases in the dog.

PMID- 8286532
TI  - Fibrinogen as a ferritin-binding protein in horse plasma.
AB  - Lower apparent concentrations of ferritin were observed in horse plasma than in
      serum using the enzyme-linked immunosorbent assay (ELISA). However, the ferritin
      concentrations in plasma and serum were increased to the same level on heating
      the samples at 75 degrees C for 15 min. These results suggest that horse plasma
      has specific ferritin-binding protein(s) which inhibit(s) the ferritin assay. The
      apparent ferritin concentrations in horse serum were markedly decreased by adding
      horse fibrinogen to the serum. It was also found that fibrinogen bound to spleen
      ferritin and inhibited the immunoassay of this protein. From these results, it
      was concluded that horse fibrinogen is one of the ferritin-binding proteins which
      inhibit the immunoassay of horse ferritin.

PMID- 8286533
TI  - Effects of 2-carboxythylgerumanium sesquioxide (Ge-132) as an immunological
      modifier of post-surgical immunosuppression in dogs.
AB  - The effect of 2-carboxythylgerumanium sesquioxide (Ge-132) as an interferon-gamma
      (IFN-gamma) inducer on post-surgical immunosuppression was evaluated from the
      immunological response augmented in canine neutrophils, macrophages and
      peripheral blood lymphocytes (PBL) using the chemiluminescence technique.
      Experimental gastrotomy was performed on dogs in two groups; one group was
      subjected to sham-surgery without any medication, and the other was treated by Ge
      132 administration at 24 hr before operation. Although the phagocytic activities
      of neutrophils, macrophages and PBL in the sham-operated group were depressed
      transiently after surgery, those in the Ge-132-administered group (Ge-132 group)
      were enhanced for a long time after surgery. It appeared that the generated free
      radical, which blocked the phagocytosis of macrophages and PBL, was activated by
      IFN-gamma. These results suggest that Ge-132 pre-treatment may be efficacious and
      useful in preventing the multifaceted clinical symptoms induced by post-operative
      immunosuppression in dogs.

PMID- 8286534
TI  - Molecular cloning and chromosomal mapping of feline p53 tumor suppressor gene.
AB  - Alterations of the p53 tumor suppressor gene have been observed in a variety of
      human and mouse tumors. For investigation of the role of this gene in tumors in
      cats, feline p53 cDNA was molecularly cloned by PCR amplifications using primers
      based on the sequences conserved among several species. The cloned cDNA appeared
      to cover approximately 90% of the open reading frame of the feline p53 gene and
      had characteristic structures in common with the p53 genes of several other
      species. The amino acid sequence similarities of the feline p53 with the human,
      mouse, rat and chicken counterparts were 82.9%, 75.6%, 76.5% and 57.2%
      respectively. Moreover, using a panel of feline x rodent somatic cell hybrids,
      the feline p53 gene was assigned to feline chromosome E1. These data will be
      useful for determining the role of the p53 tumor suppressor gene in feline
      tumors.

PMID- 8286535
TI  - Prevalence of Toxocara eggs in sandpits in Tokushima city and its outskirts.
AB  - To demonstrate the prevalence of Toxocara eggs in sandpits in Tokushima
      Prefecture, Japan, sand samples were examined. Of 46 sandpits surveyed, 29
      sandpits (63.3%) had Toxocara eggs. Sandpits in public parks and playgrounds in
      residential areas were more contaminated (87.5%) with the eggs than those in
      kindergartens, schools, and children's centers (36.4%). To examine the seasonal
      change in the contamination, sand samples obtained from five sandpits were
      examined monthly from May 1990 to April 1991. Toxocara eggs were found in the
      majority of sandpits (3/5-5/5) in the spring, early summer, and autumn. In the
      summer and winter, the rates of sandpits contaminated were lower (2/5-3/5) than
      in other seasons. Egg counts became smaller in the summer and winter, especially
      in summer. The ratio of T. canis to T. cati eggs recovered was 2:3. Fecal
      examination of 144 puppies revealed that 98 (68.0%) were positive for T. canis
      eggs. These findings show that Toxocara eggs, a possible causative agent of
      visceral larva migrans, commonly present in sandpits of the urban area. To
      prevent the contamination of sandpits with these eggs, control measures are
      needed.

PMID- 8286536
TI  - hlyIA-like sequence present in a genetic locus with low homology to appA in
      Actinobacillus pleuropneumoniae serotype 10.
AB  - Using the appA gene encoding Actinobacillus pleuropneumoniae-RTX-toxin II (ApxII)
      as a probe, Southern hybridization demonstrated the presence of appA-sequence in
      all 12 serotypes except serotype 10. Serotype 10 strains had a genetic locus with
      low homology to appA (tentatively designated Lha). DNA sequence analysis revealed
      that Lha contained a part of hlyIA gene encoding a 105-kDa hemolysin ApxI.
      Southern hybridization demonstrated the presence of Lha (hlyIA) sequence not only
      in serotype 10 but also in serotypes 1, 5a, 5b, 9, and 11, which had strong
      hemolytic activity with sheep red blood cells and were highly virulent for mice.
      These results suggest that ApxI may be associated with the virulence phenotype of
      the organism.

PMID- 8286537
TI  - Electron microscopic studies on reticular fibers in the pig sheathed artery and
      splenic cords.
AB  - The reticular fibers of the capillary sheath and splenic cord were studied in the
      pig spleen by transmission electron microscopy to reveal their components and the
      presence of sialic acid in the amorphous ground substance. Collagen fibrils,
      elastic fibers, microfibrils, nerve fibers and smooth muscle cells were observed
      in the reticular fibers of the splenic cord, while only microfibrils were
      recognized in the reticular fibers of the capillary sheath. The binding of LFA
      lectin to the splenic cord was stronger than the capillary sheath. These findings
      may suggest that the reticular fibers of the splenic cord include numerous
      functional elements and perform an important role during contraction or dilation
      of the spleen. On the other hand, it seems to be reasonable to term the capillary
      sheath as "capillary basement membranous reticular tissue", since the reticular
      fiber of the capillary sheath resembles the basement membrane of the capillary in
      its components.

PMID- 8286538
TI  - Systemic ceroid-lipofuscinosis in a Japanese domestic cat.
AB  - An 11-month-old castrated male Japanese domestic cat was euthanized because of
      neurological symptoms such as shivering and difficulty of walking.
      Histopathological examination showed glial proliferation and marked deposition of
      ceroid-lipofuscin in the neuronal and glial cells of the brain. Ceroid-lipofuscin
      was deposited also in reticuloendothelial cells of the liver, spleen and some
      lymph nodes.

PMID- 8286539
TI  - Reproduction of female Sika deer (Cervus nippon yesoensis Heude, 1884) in Ashoro
      District, Hokkaido.
AB  - The authors studied some reproductive characteristics of wild female sika deer
      (Cervus nippon yesoensis Heude, 1884) in Ashoro District, Hokkaido. Large numbers
      of females attained sexual maturation at the age of yearling, and the pregnancy
      rate of yearlings and older was 96.4% (n = 28). These high levels of fertility
      should be considered the standard for high quality populations of sika deer. The
      estrus cycle began in late October. Twinning was exceptional. Sex ratio of
      fetuses was statistically 1:1, and there was no significant difference in fetal
      weights between males and females in March. The birth weight is estimated to be
      around 6 kg. Accessory corpora lutea were found in 77.8% (n = 27) of pregnant
      females.

PMID- 8286540
TI  - Light and electron-microscopical observations of the early developmental stages
      of Theileria sergenti in the gut of Haemaphysalis longicornis.
AB  - Morphological characteristics of the early developmental stages of Theileria
      sergenti in the vector tick were observed by light and electron-microscopies and
      compared with those of other Theileria species. Just before the repletion of
      nymphs, various stages of the parasite were observed in gut contents of tick by
      light microscopy: the spherical intra-erythrocytic stage, the ring-form stage,
      the spindle-shaped stage and the round-form stage. Electron microscopy revealed
      that the spherical intra-erythrocytic stages were 1-2 microns in diameter and
      were marginally located in host erythrocytes. The organisms liberated from host
      erythrocytes into the tick gut lumen had a large nucleus, an endoplasmic
      reticulum, electron dense-organelles and a double-walled, mitochondrion-like
      organelle. In addition ticks had ray-bodies in the gut lumen. These bodies had
      short protrusions containing 1-3 microtubules and a labyrinthine structure
      containing highly electron-dense organelles, so they were considered as the
      developing microgamont of T. sergenti.

PMID- 8286541
TI  - A Ca(2+)-dependent phosphorylcholine-binding protein in chicken serum.
AB  - A Ca(2+)-dependent phosphorylcholine (PC)-binding protein in normal chicken serum
      was purified by affinity chromatography on p-aminophenyl PC-Sepharose 4B followed
      by gel filtration on Sephacryl S-300. In gel filtration, the isolated PC-binding
      protein was eluted in a symmetrical protein peak at the position of approximately
      100,000. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the
      protein was resolved into two protein bands of 31,000 and 38,000 under
      nonreducing conditions and of 40,000 and 46,000 under reducing conditions. These
      results suggest that chicken serum PC-binding protein may be composed of two
      different subunits which contain intrachain disulfide bonds.

PMID- 8286543
TI  - Theileria sergenti: transformation of zygotes into kinetes in vector ticks,
      Haemaphysalis (Kaiseriana) longicornis and H. (K.) mageshimaensis.
AB  - Invagination or transformation of a zygote of Theileria sergenti into a kinete
      was examined with Giemsa-stained smears of the midgut of vector ticks,
      Haemaphysalis longicornis and H. mageshimaensis. Zygotes invaginated almost
      simultaneously with the moulting of host ticks. They were round and oval, and
      measured 5.4 to 6.7 microns in diameter on average. The kinetes developing in the
      zygotes were situated in the periphery of cytoplasm and were spindle- or club
      shaped.

PMID- 8286542
TI  - Changes of lipid concentrations in liver and serum by administration of carnitine
      added diets in rats.
AB  - Carnitine [4,-(N,N,N-trimethyl-ammonio)-3-hydroxybutanoate] was added to the diet
      to study its effect on lipid concentrations in liver and serum of rats. In rats
      administered with a high-fat diet containing 30% corn oil, simultaneous
      administration of carnitine reduced the concentrations of triglycerides and total
      cholesterol in both liver and serum. The addition of carnitine to a high
      cholesterol diet decreased the levels of cholesterol and lipids in serum, but the
      cholesterol level to remain higher than control level. The present findings
      suggested that addition of carnitine may improve the lipid metabolism in obesity.

PMID- 8286544
TI  - Suppression of delayed-type hypersensitivity (DTH) responses in xenografts by
      pretreatment with ultraviolet (UV)-irradiated hepatocytes.
AB  - F344 Rat hepatocytes (HCs) that had been exposed to ultraviolet (UV) light were
      transplanted into the dorsal subcutaneous tissues of Balb/c mice. Four days after
      the transplantation, the anti-HC delayed-type hypersensitivity (DTH) response was
      assessed by determining the response to a direct challenge with non-irradiated
      HCs. The DTH response in mice transplanted with 600 J/m2-UVB-irradiated HCs was
      suppressed significantly compared with that with non-irradiated HCs. Furthermore,
      the DTH responses evoked by challenge with non-irradiated HCs were similar to
      those evoked by UV-irradiated HCs.

PMID- 8286545
TI  - Three-dimensional reconstruction of the pig sheathed artery.
AB  - The structure of the sheathed artery and the number of branches of the sheathed
      capillary were investigated by three-dimensional reconstruction computer graphics
      in the pig spleen. The capillary branched 1 to 6 times in the capillary sheath in
      more than 90% of all samples examined. The sheathed artery varied in shape and
      size in accordance with the number of branches and direction of the capillary.
      The usual descriptions for the sheathed artery were suggested to be mostly in
      appropriate at least for that of the pig spleen.

PMID- 8286546
TI  - Distinction between Aujeszky's disease virus-infected and vaccinated pigs by
      hemagglutination-inhibition test.
AB  - A hemagglutination-inhibition (HI) test was applied to distinguish virulent
      Aujeszky's disease virus infected pigs from those immunized with a glycoprotein
      gIII deletion vaccine. The vaccine strain, dlg92/dltk, did not have
      hemagglutination activity with mouse erythrocytes and the pigs vaccinated five
      times with the dlg92/dltk strain failed to develop HI antibody, although they
      developed neutralizing antibody with 128 to 512 titers to Aujeszky's disease
      virus. On the other hand, these pigs produced HI antibody 1 to 2 weeks after
      virulent virus inoculation. Thus the animals infected with virulent strain were
      easily differentiated from the animals immunized with the gIII deletion vaccine.

PMID- 8286547
TI  - Establishment and characterization of a feline large granular lymphoma cell line
      expressing interleukin 2 receptor alpha-chain.
AB  - A feline large granular lymphocyte (LGL) cell line was established from a cat
      with an alimentary-form lymphoma. This cell line, designated as FGL, had many
      large azurophilic granules in the cytoplasm, which were typical to LGL cells.
      Proviral genome of feline leukemia virus was detected in the chromosomal DNA of
      FGL cells, and reverse transcriptase activity was also demonstrated in the
      culture supernatant. Furthermore, we found expression of interleukin 2 (IL-2)
      receptor alpha-chain on the cell surface of FGL and its natural killer activity
      against human erythroblastic leukemia cell line, K562.

PMID- 8286548
TI  - Vertical transmission of Hepatozoon canis in dogs.
AB  - We experienced vertical infections of puppies with Hepatozoon canis from 1990 to
      1992. In 23 of 29 (79.3%) puppies from a total of 6 deliveries, gamonts or
      meronts were detected from 16 to 60 days after birth. The mother dogs were
      delivered of the puppies under tick-free conditions treated with an acaricide.
      There was no chance of infection of the puppies with H. canis after birth.
      Therefore, the vertical transmission of H. canis was supposed to be established
      in the family of dog.

PMID- 8286549
TI  - First incidence of multilocular echinococcosis in a race horse in Japan.
AB  - Nodular hepatic lesions caused by larval Echinococcus multilocularis were found
      in a four-year-old female thoroughbred race horse born and raised in Hokkaido.
      Before detection of the infection, the infected animal was transported around
      Honshu for racing. The present disclosure of hydatidosis in a race horse raises
      concern over the potential danger of spreading the infection throughout Japan by
      horses possibly infected in Hokkaido.

PMID- 8286550
TI  - Secondary antibody response to Haemophilus somnus antigen in breeding Japanese
      black cattle fed selenium-deficient and alpha-tocopherol-fortified diets.
AB  - The cattle with adequate alpha-tocopherol (Vit E) and marginally deficient
      selenium (Se) status manifested significantly lower anti-Haemophilus somnus
      antibody titer than the cattle supplemented with Se in the later stage of an 8
      week trial. However, in the early stage no difference was observed in magnitude
      of anti-H. somnus antibody development between them. These results suggested that
      Se may contribute to anti-H. somnus antibody production, and that Vit E can make
      up for Se deficiency to a certain degree.

PMID- 8286551
TI  - Magnetic resonance imaging in a dog with choroid plexus carcinoma.
AB  - Choroid plexus carcinoma was diagnosed in a 10-year-old maltese dog with chief
      complaint of progressive ataxia and head tilt. No abnormalities was observed on
      hemogram, radiographs of the skull, and electroencepharograph (EEG). Neurological
      examination suggested central vestibular lesions. On the magnetic resonance
      imaging (MRI) examination, images after contrast enhancement with Gadolinium DTPA
      dimeglumine showed a rough circular lesion with an increased signal intensity in
      caudal fossa. This lesion was histopathologically confirmed to be choroid plexus
      carcinoma.

PMID- 8286552
TI  - Seasonal periodical appearance of Hepatozoon canis gamont in the peripheral
      blood.
AB  - We investigated the appearance of gamonts in peripheral leukocytes of 13
      Hepatozoon canis infected dogs from June 1990 to December 1992. In almost all the
      dogs, the numbers of gamonts increased from spring to autumn, and decreased from
      autumn to winter. Particularly in the dogs used for hare hunting, a large number
      of gamonts was detected from spring to autumn. This finding reveals that the
      gamont increases in number in the dog which ingested the infected ticks during
      the hunting season.

PMID- 8286553
TI  - Protein analysis of Strongyloides venezuelensis by two-dimensional polyacrylamide
      gel electrophoresis.
AB  - Infective larvae, larvae in the lung and adult-stage worms in the small intestine
      of Strongyloides venezuelensis were analysed for protein by two-dimensional gel
      electrophoresis. The infective larvae were differentiated from the other two
      stages of parasite with 13 stage-specific spots, whereas the larvae in the lung
      and the adult-stage worms were identical to each other in spot patterns except
      for 6 spots.

PMID- 8286554
TI  - A survey of an antibody to reticuloendotheliosis virus in sera of chickens and
      other avian species in Japan.
AB  - An examination of antibody to reticuloendotheliosis virus (REV) in sera of
      chickens and other avian species collected from various districts in Japan was
      carried out. Agar gel immunodiffusion test (AGID) to the chicken sera revealed
      positive results in 25.9% of the 54 farms, 21.4% of the 126 flocks and 14.3% of
      the 1,892 individual chickens. All the AGID positive sera also were positive in
      indirect immunofluorescence and/or virus neutralization tests. In avian species
      other than chickens, Peking ducks (1/120; 0.4%) and pheasants (4/27; 14.8%) were
      AGID test positive. This is the first study conducted in Japan.

PMID- 8286555
TI  - Development to the blastocyst stage of pig embryos cultured in the amniotic fluid
      of developing chick embryos.
AB  - Early-stage pig embryos were collected from superovulated donor gilts (60-72 hr
      post hCG injection) and co-cultured in modified Brinster medium for ovum culture
      (mBMOC-2) + porcine oviduct epithelial cells (POEC) or in the amniotic fluid of a
      developing chick embryo (CEAm). The development rate to the compacted morulae or
      blastocyst stage was significantly higher (P < 0.01) in embryos co-cultured in
      CEAm (60.0%) than those co-cultured in mBMOC-2 + POEC (18.0%). The results
      indicate that CEAm could be used for production of compacted morulae or
      blastocysts from early-stage pig embryos. This culture system could also be
      valuable in situations where a CO2 controlled incubator is not available.

PMID- 8286556
TI  - Appearance of haptoglobin in serum from cows at parturition.
AB  - Haptoglobin (Hp) concentrations were evaluated in 42 cow sera at around
      parturition by single radial immunodiffusion using anti-cow Hp rabbit serum. At
      parturition, Hp was detected in 31 of 42 cows. The detection rate (74%) was
      significantly higher than those before (0-10%) and after parturition (5-21%). At
      parturition, serum concentrations of cortisol and non-esterified fatty acids were
      significantly higher than those before and after parturition. A significantly
      lower concentration of serum triglycerides at parturition, compared to the values
      before parturition, was also observed. From these results, Hp is considered to be
      associated with fatty liver development of cows, because fatty liver particularly
      occurs in the peripartum period.

PMID- 8286557
TI  - Immunohistochemical investigations of lymphocytes in the lymphoid organs of
      cyclophosphamide treated chickens.
AB  - The localization of lymphocytes in the lymphoid organs of cyclophosphamide (Cy)
      treated chickens and untreated control chickens was compared
      immunohistochemically using a variety of monoclonal antibodies (CT3, 2-6, 11-39,
      TCR1, TCR2, TCR3, L22, 11G, 3E8, B-4D-4, A-13). In the Harderian glands of Cy
      treated chickens, an an increase of T cells was observed, though T cells were a
      few in untreated controls. These increased T cells consisted of CD4 positive or
      CD8 positive cells. Further, these T cells were stained with TCR2 or TCR3
      antibody, and a small number of cells were stained with TCR1 antibody. In other
      lymphoid organs such as the bursa of Fabricius, thymus, spleen and cecal tonsils,
      B lymphocyctes severely decreased or disappeared in Cy treated chickens, though
      no significant alteration in T cell distribution was observed.

PMID- 8286558
TI  - Effect of active egg white product on neutrophil function in weanling piglets.
AB  - The effect of oral administration of an active egg white product (AEWP) on
      neutrophil function in weanling piglets was investigated. The peripheral blood
      neutrophils of piglets receiving single doses of 20 mg/kg and 100 mg/kg displayed
      increased phagocytic activity for latex particles from 1 day after
      administration. This increased phagocytic activity persisted for 5 days in the
      100 mg/kg group. Piglets receiving a dose of 30 mg/kg/day for a week displayed
      increased neutrophil phagocytic activity throughout the administration period.
      Moreover, when the administration of AEWP was resumed 10 days after withdrawal,
      neutrophil phagocytic activity rapidly increased again. Thus, AEWP enhanced the
      nonspecific phagocytic activity of neutrophils when given to piglets by the oral
      route.

PMID- 8286559
TI  - Immune response after surfactant treatment of newborn infants with respiratory
      distress syndrome.
AB  - We examined the sera of 68 newborn infants with respiratory distress syndrome; 49
      were treated with a natural porcine-derived surfactant preparation and 19 were
      controls. Serum of the patients was collected before, 3 weeks and 3 months after
      surfactant treatment. To detect any antibody that had been raised, we applied
      diluted serum of the babies in an indirect immunoperoxidase staining technique on
      frozen pig lung tissue specimens. With light microscopy an immune response could
      be appreciated as a brown reddish deposit in the porcine lung tissue specimens in
      4 out of the 49 surfactant-treated and not in the control babies.

PMID- 8286560
TI  - Expression of CD45R0 antigen on the surface of resting and activated neonatal T
      lymphocyte subsets.
AB  - Expression of CD45R0 antigen has been evaluated on the surface of T lymphocyte
      subsets obtained from cord blood and on peripheral blood lymphocytes (PBL) from
      both term and preterm neonates. In some experiments, expression of the same
      antigen has also been evaluated after in vitro activation of cord blood
      lymphocytes (CBL) with phytohemagglutinin (PHA) or in mixed lymphocyte culture.
      The CD45R0 molecule was found to be present on a significantly lower percentage
      of CD3+, CD4+ and CD8+ CBL as compared with the same subsets evaluated in adult
      individuals. Moreover, at variance with adult PBL, the great majority of CBL
      displayed a low level of fluorescence when stained with UCHL1 (CD45R0-specific
      monoclonal antibody), and both PHA and allogeneic stimuli were able to strongly
      increase the expression of the CD45R0 molecule on CBL. The percentage of CD45R0+
      PBL obtained from both term and preterm neonates on the 1st day of life was
      comparable to that of CBL, however the expression of this molecule increases
      remarkably within a few days in the majority of term neonates, while it seems to
      take more time for the antigen to be fully expressed in preterm infants.

PMID- 8286561
TI  - Transport of triiodothyronine by erythrocytes from premature and term infants.
AB  - To analyze hypothyroxinemia in low birth weight (LBW) infants, the initial uptake
      of T3 into erythrocytes from term and premature infants was measured. Thirty
      eight infants and 18 prepubertal children as controls were subjected in this
      study. The infants were divided into group 1 (premature infants; below 2,500 g, n
      = 12) and group 2 (term infants; 2,501-3,500 g, n = 26). Infants with LBW for
      gestational age were excluded from this study. Vmax for group 1 (mean +/- SE, 6.4
      +/- 0.5 pmol/min/10(8) cells), having low thyroid hormone levels, was
      significantly less than in group 2 (9.0 +/- 0.7 pmol/min/10(8) cells; p < 0.05).
      Mean Vmax for both groups exceeded normal controls (3.9 +/- 0.3 pmol/min/10(8)
      cells; p < 0.01). Km in the perinatal period varied widely and was essentially
      the same as in the normal controls. These findings indicate that T3 uptake by
      erythrocytes of newborns may possibly be high regardless of maturation stage and
      blood levels of thyroid hormones may be reflected not by change in the affinity
      of the transport system but by that in the number of membrane carriers.

PMID- 8286562
TI  - Effect of opioid-induced analgesia on beta-endorphin, cortisol and glucose
      responses in neonates with cardiorespiratory problems.
AB  - The effects of analgesia on plasma beta-endorphin (beta-E), serum cortisol and
      blood glucose responses were investigated in 20 distressed, mechanically
      ventilated neonates during the first 3 days of life. Morphine 0.1 mg/kg,
      meperidine 1 mg/kg or alfentanil 10 micrograms/kg were used for analgesia as
      clinically indicated. Plasma beta-E, serum cortisol and blood glucose were
      recorded before analgesia and 1 and/or 2, 12 and 24 h afterwards in the distress
      group and once in 20 healthy neonates (control group). beta-E, cortisol, and
      blood glucose before analgesia were significantly higher in the distress group
      than in the control group. Cortisol values had decreased significantly 2 h after
      analgesia and blood glucose within 12 h. Plasma beta-E values had decreased to
      the same level as in the controls 24 h after the start of analgesia. The results
      indicate that the stress response in the distressed neonates with
      cardiorespiratory problems, as assessed by beta-E, cortisol, and blood glucose,
      is attenuated by opioid medication, and it is concluded that these patients
      should be given adequate analgesia.

PMID- 8286563
TI  - Ontogeny of rat lung type IV collagenase mRNA expression and collagenolytic
      activity during the perinatal period.
AB  - The extracellular matrix is important in the cellular differentiation and
      morphogenesis of the lung. The basement membrane (BM), an integral part of the
      extracellular matrix, is composed primarily of type of IV collagen. The
      metabolism of type IV collagenase is important in remodeling of BM that occurs
      during growth. We examined the ontogeny of rat lung type IV collagenase mRNA
      expression, type IV collagenolytic activity and type IV collagen content during
      the perinatal period. In addition, the effect of prenatal glucocorticoid (GC)
      treatment on fetal lung type IV collagenase mRNA expression and type IV
      collagenolytic activity was studied. Lung polyadenylated RNA was extracted and
      subjected to Northern blot analysis and laser densitometry after hybridization
      with human type IV collagenase (approximately 72 kD) and rat actin cDNA probe.
      Type IV collagenolytic activity and type IV collagen concentration were
      quantitated by an enzymatic and a radioimmunoassay, respectively. While lung type
      IV collagenase mRNA to alpha-actin ratio and type IV collagenolytic activity were
      highest prior to birth (21-day fetus), the lung type IV collagen concentration
      was lowest at this time. Prenatal GC treatment did not influence type IV
      collagenase mRNA expression or the collagenolytic activity. A role for fetal lung
      type IV collagenase in preparation for the neonatal pulmonary vascular and/or
      alveolar adaptation is proposed.

PMID- 8286564
TI  - Induction and distribution of cellular retinol-binding protein, type two during
      villus-crypt development in the chick duodenum.
AB  - Between day 18 of embryogenesis and 1 day posthatch, a rapid and remarkable (over
      10-fold) increase in cellular retinol-binding protein, type two (CRBP(II)) levels
      occurred in the lower portion of duodenal villi of the chick. With further
      postnatal growth and concomitant with initiation of food intake, CRBP(II) levels
      increased over 2-fold in the mid-villus enterocytes. The results suggest that a
      first induction of CRBP(II) occurs in differentiating lower villus enterocytes
      during the perinatal period and is followed by marked increases in mid-villus
      cells. These quantitative change in the distribution and levels of CRBP(II) are
      probably related to the appearance of retinol in the duodenal lumen.

PMID- 8286565
TI  - Effect of the progesterone-induced serpin-like proteins of the sheep endometrium
      on natural-killer cell activity in sheep and mice.
AB  - Natural killer (NK)-like cells have been implicated as an important component of
      the endometrial lymphoid cell population and have been suggested to play roles in
      resistance to viral infection, in abortion, and in fetal growth. Inhibition of
      endometrial NK cell activity may be an important aspect of successful pregnancy
      because of the potential for actions directed against the conceptus. The aim of
      the study reported here was to test the hypothesis that the uterine milk proteins
      (UTM-proteins) inhibit activity of NK cells. Physiological concentrations of
      enriched preparations of UTM-proteins, which are a pair of related proteins that
      represent the major lymphocyte-inhibitory molecules in uterine fluid of pregnant
      and progesterone-treated ewes, were found to inhibit cytotoxic activity of
      cultured sheep and mouse NK cells. Furthermore, injection of the proteins into
      mice reduced activity of basal and poly(I).poly(C)-induced NK activity in spleen
      and prevented a slight increase in fetal loss caused by injection of
      poly(I).poly(C). These results further implicate the UTM-proteins as important
      regulators of uterine immune function.

PMID- 8286566
TI  - Effect of time of mating relative to ovulation on morphological diversity of
      swine blastocysts.
AB  - The effect of time of mating relative to ovulation on the amount of embryonic
      diversity was investigated in 37 mature crossbred gilts. Ovulation was induced by
      injecting proestrous gilts with 1000 IU of hCG. Gilts were naturally mated once
      at 24-32 (control), 41, or 43 h after hCG injection (n = 10, 9, and 18,
      respectively). Blastocysts were collected surgically 288 h post-hCG from gilts
      mated at 24-32 h post-hCG, from those mated at 41 h post-hCG, and from 8 of those
      mated at 43 h post-hCG. Collection of blastocysts was performed at 295 h in 10
      gilts mated at 43 h post-hCG. Blastocysts within the ranges 1.0-4.0, 4.5-7.0, 7.5
      10.0, 10.5-15.0, and 15.5-40.0 mm and those > 40.0 mm were classified
      morphologically as small, medium, and large spheres and as ovoidal, tubular, and
      filamentous, respectively. Blastocysts were incubated for 6 h to quantify
      secretion of estradiol-17 beta (estradiol). Morphological diversity (standard
      deviation of size) did not differ among blastocysts of treatment groups. Delaying
      the time of mating reduced (p < 0.07) the subsequent size and estradiol secretion
      of blastocysts. Waiting until 295 h after hCG to evaluate blastocysts of gilts
      mated at 43 h resulted in blastocysts size and estradiol secretion similar to
      that of conception of controls. Estradiol secretion by medium and large spherical
      blastocysts of gilts mated at 43 h post-hCG and evaluated at 288 h was lower (p <
      0.05) than that by blastocysts of the same classifications from
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286567
TI  - Gonadotrope responsiveness in orchidectomized sheep: III. Effect of estradiol
      withdrawal after continuous infusion.
AB  - The magnitude of GnRH-induced (1600 ng/hourly pulse for 24 h) preovulatory surge
      like secretion of LH was assessed in orchidectomized sheep (wethers) during
      infusion of estradiol (E2, 5 micrograms/h in 10% ethanol-saline [vehicle]) or at
      0, 12, 24, or 48 h after E2 withdrawal (n = 6 wethers/group). In one group,
      infusion of E2 was continued for 48 h, with concurrent circhoral delivery of GnRH
      during the final 24 h of the E2 delivery period. In other treatment groups,
      infusion of E2 or vehicle was continued for 24 h. Circhoral delivery of GnRH was
      initiated at the conclusion of E2 delivery or 12, 24, or 48 h thereafter, or at
      48 h after cessation of vehicle infusion. Total GnRH-induced LH secretion in
      wethers receiving concurrent E2 was significantly augmented relative to the GnRH
      induced secretory response in wethers receiving vehicle alone. The magnitude of
      GnRH-induced LH release was significantly reduced in animals in which E2 delivery
      was halted at the beginning of the GnRH challenge period. Further reductions in
      gonadotrope responsiveness were noted 12, 24, and 48 h after cessation of E2
      delivery. Responsiveness 48 h after halting the E2 infusion did not differ (p >
      0.05) from the responsiveness of wethers that had not been treated with E2. In a
      companion study, anterior pituitary tissue was collected at the end of E2
      infusion (5 micrograms/h for 24 h) or at 12, 24, or 48 h thereafter (n = 6
      wethers/group). Anterior pituitary tissue of control animals (n = 6) was
      collected after halting the infusion of vehicle alone.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8286568
TI  - Plasma concentrations of immunoreactive inhibin and gonadotropins following
      removal of ovarian follicles in the domestic hen.
AB  - In the domestic hen, the preovulatory follicles are arranged in a hierarchy. The
      largest (F1) follicle ovulates first, the second largest (F2) follicle ovulates
      approximately 26 h later, and so on. The nature of this regulation is not known.
      Inhibin has been implicated in the feedback regulation of FSH in mammals, and
      bioactive as well as immunoreactive inhibin has been demonstrated in chickens.
      The present experiments were conducted with two aims: 1) to determine the plasma
      level of immunoreactive inhibin in response to removal of various numbers of
      preovulatory follicles and 2) to assess the gonadotropin response to such
      follicle removal. In experiment 1, the F1 (n = 4), F1 + F2 (n = 5), F1 + F2 + F3
      (n = 5), and F1 + F2 + F3 + F4 (n = 4) follicles were removed surgically. Sham
      operated animals served as controls. Blood samples were taken at time 0 (prior to
      surgery) and at 6, 24, and 48 h after surgery. In experiment 2, animals were sham
      operated (n = 5) or the F1-F4 (n = 4) or F1-F4 plus small yellow follicles (SYF;
      n = 5) were removed. Blood samples were removed at time 0 and at 3, 6, and 24 h
      and at daily intervals until Day 10 after surgery. In both experiments, plasma
      immunoreactive inhibin was significantly lowered (p < 0.001) and plasma FSH was
      acutely increased (p < 0.05) by follicle removal. Plasma LH was decreased at some
      time points after follicle removal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286569
TI  - Epidermal growth factor and insulin induce the proliferation of guinea pig
      endometrial stromal cells in serum-free culture, whereas estradiol and
      progesterone do not.
AB  - Guinea pig endometrial stromal cells were cultured in serum-free medium to assess
      the effects of growth factors and ovarian steroids on cell proliferation. When
      the cells were made quiescent by serum depletion, [3H]thymidine incorporation was
      increased by the addition of insulin plus epidermal growth factor (EGF), reaching
      a peak after 24 h of stimulation. This effect was dose-dependent. Both factors
      acted synergistically. Estradiol-17 beta (E2), either alone or with various
      concentrations of growth factors, had no mitogenic effect. Thus, cell
      proliferation appeared to be estrogen-insensitive, despite a high level of
      estrogen receptors (19,000 sites per cell). The integrity of these receptors was
      checked by transfecting cells with a plasmid containing an estrogen-responsive
      element linked to a CAT gene: E2-induced CAT activity was reduced by the
      antiestrogen ICI 164,384. Despite the presence of progesterone receptors, the
      cells, either primed with E2 or not, were not growth-stimulated by progesterone.
      E2 had no effect on cells cultured in the presence of dextran-coated charcoal
      stripped serum. Thus, whatever the culture conditions, stromal cells with
      functional estrogen receptors were insensitive to the putative mitogenic effects
      of E2 and progesterone. However, they were highly responsive to the mitogenic
      effects of insulin and EGF.

PMID- 8286570
TI  - Sertoli cell and germ cell cystatin C: stage-dependent expression of two distinct
      messenger ribonucleic acid transcripts in rat testes.
AB  - Sertoli cells were shown to synthesize and secrete cystatin C, a potent inhibitor
      of cysteine proteases. The evidence for this observation was obtained from
      protein sequencing. Western analysis using antiserum specific to cystatin C, and
      immunoprecipitation of 35S protein secreted by cultured cells. The Western
      analysis with an antiserum to human cystatin C showed that cultured Sertoli cells
      secrete three previously reported immunoreactive forms of cystatin C: a
      predominant pair of proteins at 13-14 kDa and a less abundant 20-kDa protein.
      Immunohistochemical localization of cystatin C in sections of rat testes showed
      intense staining in Sertoli cells; no immunoreactivity was observed in
      spermatogonia or spermatocytes. A cDNA fragment for rat cystatin C was obtained
      by use of the polymerase chain reaction and was used as a probe in Northern
      analyses to examine the steady-state levels of cystatin C mRNA in intact testes
      and in Sertoli and spermatogenic cells. Sertoli cells contained a 700-nucleotide
      cystatin C transcript, and a mixed population of spermatids and spermatocytes
      contained a 550-nucleotide transcript. Analysis of RNA from purified
      spermatogenic cells revealed that round and condensing spermatids contained the
      550-nucleotide transcript, while pachytene spermatocytes contained a smaller 500
      nucleotide transcript. The 700-nucleotide transcript was present in testes
      isolated from rats of 5-79 days of age, the 500-nucleotide transcript was
      detected initially in testes from 24-day-old rats, and the 550-nucleotide
      transcript was detected initially at 35 days of age. Both the 500- and 550
      nucleotide transcripts increased in abundance until 50 days of age. RNA from
      stage-synchronized testes showed that steady-state levels of both the 550- and
      700-nucleotide transcripts were lowest in stages VI-VII of the cycle. These data
      suggest that the role of cystatin C in the testis may be to inhibit the
      proteolytic activity of the cysteine protease cathepsin L in all stages except
      stages VI-VII.

PMID- 8286571
TI  - Mouse Sertoli cells secrete mannose 6-phosphate containing glycoproteins that are
      endocytosed by spermatogenic cells.
AB  - Sertoli cells were isolated from prepubertal mice and cultured in serum-free
      medium to determine whether they secrete glycoproteins containing mannose 6
      phosphate (M6P). Assays of the conditioned medium for lysosomal enzyme
      precursors, which typically bear the M6P recognition marker, indicated that
      Sertoli cells selectively secreted beta-N-acetylhexosaminidase and alpha
      mannosidase, but not beta-glucuronidase or beta-galactosidase. Sertoli cells were
      labeled metabolically with [35S]methionine and the conditioned medium was
      fractionated on a cation-independent M6P receptor affinity column. Most of the
      secreted proteins did not bind to the column (peak A); however, approximately 10%
      of the radioactivity eluted as a low-affinity fraction (peak B), and 5-11% of the
      recovered cpm bound to the column and were eluted with 2.5 mM M6P (peak C). The
      radiolabeled proteins in each fraction were analyzed by one- and two-dimensional
      electrophoresis and fluorography. Two protein bands with molecular weights of
      30,000 and 35,000 were present in peak B. Peak C contained at least ten M6P
      containing glycoproteins with molecular weights between 30,000 and 135,000 and
      isoelectric points < 6.5. The 35,000-molecular-weight constituent prominent both
      in peaks B and C was identified as procathepsin L by immunoprecipitation with a
      specific antibody. When pachytene spermatocytes and round spermatids were
      cultured overnight in the presence of peak C glycoproteins radiolabeled with
      125I, both germ cell types accumulated these Sertoli M6P-glycoproteins by a
      receptor-mediated process that was specifically inhibited by M6P. The Sertoli M6P
      glycoproteins taken up by germ cells were processed to lower molecular weight
      forms. These results provide evidence that M6P receptors on the surface of
      spermatogenic cells endocytose secrete glycoproteins that are likely to be
      present in the seminiferous epithelium.

PMID- 8286572
TI  - Retinol-binding protein gene expression in cyclic and pregnant endometrium of
      pigs, sheep, and cattle.
AB  - Retinol-binding protein (RBP) is a major secretory product of conceptuses and
      endometrium of the large domestic animals. The present study examined the
      abundance of RBP mRNA in cyclic and early pregnant endometrium of pigs, sheep,
      and cattle and confirmed the presence of RBP mRNA in preiimplantation conceptuses
      of the large domestic animals. Northern blot analysis, using porcine liver RBP
      cDNA as the probe, detected a 1.0-1.1-kb transcript in conceptuses and
      endometrium collected during the preiimplantation period of pregnancy in pigs
      (Day 15), sheep (Day 16), and cows (Day 18). Slot-blot analysis of RBP mRNA in
      endometrium of pigs, sheep, and cows indicated differential RBP gene expression
      across days and statuses in pigs and sheep and across days alone in cows. In
      pigs, RBP gene expression was low to undetectable at Days 0, 5, and 10 of the
      estrous cycle and Day 10 of pregnancy. Levels of RBP mRNA increased (p < 0.06)
      from Days 10 to 12 and further (p < 0.001) to Day 15 across both statuses. At Day
      18, RBP mRNA levels decreased (p < 0.01) in cyclic pigs but remained elevated in
      endometrium of pregnant pigs. In sheep, levels of RBP mRNA increased between Days
      10 and 12 and 14 in both cyclic and pregnant ewes; however, between Days 14 and
      16, RBP mRNA levels remained elevated in cyclic endometrium but decreased (p <
      0.01) in endometrium of pregnant ewes. In a second experiment, RBP mRNA levels
      increased (p < 0.01) between Days 0-5 and Days 13-15 of the estrous
      cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286573
TI  - Atrial natriuretic factor activates cyclic adenosine 3',5'-monophosphate
      phosphodiesterase in Xenopus laevis oocytes and potentiates progesterone-induced
      maturation via cyclic guanosine 5'-monophosphate accumulation.
AB  - Xenopus oocytes were found to express atrial natriuretic factor (ANF) receptors
      that activate guanylate cyclase and stimulate cyclic guanosine 5'-monophosphate
      (cGMP) production in a dose- and time-dependent manner. A truncated fragment of
      ANF, known to bind to mammalian ANF receptors without stimulating cGMP
      accumulation, did not elicit a cGMP response in oocytes. In addition,
      preincubation with ANF increased the number of oocytes that underwent
      progesterone-induced maturation. The maximally effective dose of ANF (1 microM)
      elevated intracellular and extracellular cGMP accumulation from 50 to 200 and 5
      to 800 fmol/oocyte, respectively, and increased the number of maturing oocytes by
      up to 3-fold. ANF's effects on progesterone-induced maturation were mimicked by
      nonhydrolyzable analogues of cGMP. ANF and 8-Br-cGMP had no effect on maturation
      in the absence of progesterone, indicating that elevation of cGMP alone is not
      sufficient to induce maturation. Dibutyryl-cGMP was as effective as 8-Br-cGMP,
      whereas 8-Br-guanosine monophosphate, 8-Br-guanosine, and 8-Br-cyclic inosine
      monophosphate did not potentiate ovum maturation. In Xenopus oocytes, an initial
      step in progesterone-induced maturation is the reduction of intracellular cAMP
      levels; both ANF and 8-Br-cGMP lowered cAMP levels and enhanced progesterone's
      ability to do so. This decrease in cAMP levels was attributable to increased cAMP
      phosphodiesterase activity, which was enhanced by both ANF and 8-Br-cGMP. These
      findings, and the presence of functional ANF receptors on Xenopus oocytes,
      demonstrate that ANF can participate in ovum development by stimulation of cGMP
      accumulation and activation of cAMP phosphodiesterase, thereby potentiating
      progesterone's ability to decrease cAMP levels and promote ovum maturation.

PMID- 8286574
TI  - Effect of deoxyribonucleic acid protamination on fluorochrome staining and in
      situ nick-translation of murine and human mature spermatozoa.
AB  - A major event in enhancing sperm chromatin stability is the replacement of the
      histones by protamines during spermiogenesis. In this study, we present results
      indicating that chromomycin A3 (CMA3) can be used to show protamine deficiency in
      sperm chromatin. Fixed chromatin of mature mouse spermatozoa showed high
      fluorescence after treatment with ethidium bromide (EB), but was completely
      unstained after treatment with CMA3. The same chromatin was found to be highly
      resistant to in situ nick-translation. In contrast, a substantial fraction of
      human spermatozoa were positive for CMA3. The accessibility of CMA3 to the DNA of
      human sperm was eliminated if the slides were previously treated with protamine
      in situ. This treatment did not affect the accessibility of EB to the chromatin.
      Individual human sperm samples revealed a substantial frequency of spermatozoa
      with endogenous nicks, which was found to be the same as the frequency of
      spermatozoa responding positively to CMA3 staining. Treatment of preparations
      with protamines prevented the identification of the endogenous nicks. These data
      as a whole suggest that CMA3 could represent a useful tool for the detection of
      protamine deficiency in sperm chromatin. Furthermore, confirmation of experiments
      relating sensitivity to nick translation and positivity to CMA3 may allow an
      indirect in situ visualization of nicked and partially denatured DNA, which could
      correlate with certain forms of male factor infertility.

PMID- 8286575
TI  - Season of the year influences concentration and pattern of gonadotropins and
      testosterone in circulation of the bovine male.
AB  - Serum concentrations of LH vary with season of the year in ovariectomized beef
      and dairy cows. The objective of the present study was to determine whether
      concentrations and profile of the gonadotropins and testosterone (T) in
      circulation vary with season of year in bovine males of a composite breed type
      (beef). Five INTACT and five gonadectomized (GNX) males that were 22 mo of age at
      the initiation of the study were used. All of the males utilized were maintained
      on pasture throughout the year at the latitude of 41 degrees N. Blood samples
      were collected in a serial regimen (10-min intervals for 24 h) at the spring and
      fall equinox and the summer and winter solstice. Concentrations of LH were
      quantified in all samples, and concentrations of T were determined in all samples
      of the INTACT group. Concentrations of FSH and 17 beta-estradiol (E2) were
      quantified in pooled samples for all animals, while concentrations of T were
      determined in pooled samples for males from the GNX group. Pulse frequency of LH
      or T and mean concentration of FSH did not vary with season of the year. A
      seasonal effect on mean concentration of LH (p < 0.01) occurred in males of the
      GNX group, with mean concentrations of LH being greatest during the spring
      equinox and lowest during the winter solstice. Season had an effect on pulse
      amplitude of LH (p < 0.01), mean concentration of T (p < 0.01), and pulse
      amplitude of T (p < 0.05) in males from the INTACT group.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8286576
TI  - Progesterone, 17 beta-estradiol, and opioid neuropeptides modulate pattern of
      luteinizing hormone in circulation of the cow.
AB  - The working hypothesis for this study was that 17 beta-estradiol (E2),
      progesterone (P4), and opioid neuropeptides modulate frequency of pulsatile
      release of LH during the luteal phase of the bovine estrous cycle. On Day 8 of
      the estrous cycle (Day 0 = estrus), 20 cows were ovariectomized (OVX) and
      immediately received one of three steroid replacement treatments: P4 alone (n =
      6), E2 alone (n = 7), or P4 and E2 (n = 7). To characterize the pattern of LH in
      peripheral circulation, serial blood samples were collected (12-min intervals for
      22 h) on the fifth day following OVX. LHRH was administered after the 22-h sample
      was taken. Naloxone (opioid neuropeptide antagonist; 0.5 mg/kg) was administered
      on the sixth day after OVX, and change of concentration of LH in peripheral
      circulation was monitored. Pulse frequency of LH and mean concentration of LH
      were lower (p < 0.01) in cows treated with P4 and E2 compared to cows treated
      with P4 alone. Moreover, cows treated with E2 alone had a greater (p < 0.01)
      frequency of LH pulses and mean concentration of LH compared to cows treated with
      P4 alone. The greatest amplitude (p < 0.01) of LH release after LHRH was in cows
      treated with E2 alone. The greatest percentage increase (p < 0.01) in LH after
      administration of naloxone occurred in cows treated with P4 alone.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8286577
TI  - Pregnancy rate is greater when the corpus luteum is present during the period of
      progestin treatment to synchronize time of estrus in cows and heifers.
AB  - Our hypothesis was that conception in bovine females would be enhanced if the
      corpus luteum was present during the period of progestin treatment to synchronize
      estrus. In this study, 67 heifers (one replicate) and 124 cows (two replicates)
      were randomly assigned to one of two treatment groups. Seven days after estrus
      (Day 0), all animals were implanted with norgestomet and the implant remained in
      place for 10 days. All implants were removed on Day 17. Cows and heifers in one
      group received prostaglandin F2 alpha (PGF2 alpha) on Day 7 of the estrous cycle
      (PG 7; norgestomet without corpus luteum), and animals in the second group
      received PGF2 alpha on Day 17 (day of implant removal; PG 17; norgestomet with
      corpus luteum). All heifers and cows exhibiting behavioral estrus were
      artificially inseminated 12 h after estrus was detected during a 7-day period
      following removal of norgestomet. Blood samples were collected from cows of
      replicate 1 to determine serum concentrations of progesterone and 17 beta
      estradiol. Percentage of females that had calves as a result of artificial
      insemination was greater (p < 0.01) in the PG 17 group (87% and 78% cows [two
      replicates] and 58% heifers) compared to the PG 7 group (31% and 44% cows [two
      replicates] and 41% heifers).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286578
TI  - Restoration of spermatogenesis by follicle-stimulating hormone despite low
      intratesticular testosterone in photoinhibited hypogonadotropic Djungarian
      hamsters (Phodopus sungorus).
AB  - By exposing male Djungarian hamsters to short-day photoperiods, a
      hypogonadotropic condition resembling that of hypophysectomized animals can be
      achieved without resorting to surgery. By use of this animal model, differential
      effects of gonadotropins on spermatogenesis have been studied revealing that FSH
      selectively restimulates spermatogenesis up to the level of spermatids. In the
      present study, we investigated whether FSH (6 IU/day) also restores fertility in
      hamsters exposed to short-day photoperiods (8L:16D). Animals kept under long-day
      photoperiod (16L:8D) served as controls. After 8 wk under 8L:16D, gonads were
      involuted and the animals (n = 9-10 per group) were treated with FSH, or
      testosterone implants, or both for the following 33 days. An additional group
      received FSH for 33 days and, for the last 12 days only, FSH plus testosterone to
      induce copulatory and ejaculatory behavior. The implants caused no increase in
      intratesticular testosterone as compared to that in short-day controls. All males
      were paired with adult females for the last 5 days of treatment, and killed
      thereafter. Litter sizes were determined 22 days later. The examination of the
      testes by flow-cytometrical techniques revealed qualitatively normal
      spermatogenesis in animals receiving FSH, whereas testosterone caused an
      insignificant increase to a few round spermatids. In most FSH-treated animals,
      sperm were present in the epididymides. In hamsters receiving FSH along with
      testosterone, treatment resulted in restoration of full fertility as compared to
      long-day controls. Fertility was also restored in animals receiving testosterone
      only for the last 12 days of FSH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286579
TI  - A phytoestrogen diet induces the premature anovulatory syndrome in lactationally
      exposed female rats.
AB  - The effects of a phytoestrogen diet on sexual differentiation were examined in
      lactationally exposed rat pups. Rat dams were provided a semipurified diet
      containing the isoflavonoid coumestrol at a concentration (0.01%) previously
      found to be uterotrophic. Coumestrol treatment did not significantly alter the
      time of vaginal opening, although vaginal opening did occur at a lighter body
      weight. By 132 days of age, 83% of coumestrol-treated females exhibited the
      cornified smears of a persistent estrous state. By contrast, 91% of control
      animals were cycling regularly at 132 days of age. Estradiol stimulation failed
      to elicit an LH elevation in the coumestrol-treated animals, suggesting the
      possibility of neuroendocrine impairments. These findings indicate that the
      female offspring of mothers fed a low-level phytoestrogen diet during lactation
      manifest early and nearly universal disruption of cyclicity of the persistent
      estrus type.

PMID- 8286580
TI  - Junction-related Sertoli cell cytoskeleton in testosterone-treated
      hypophysectomized rats.
AB  - Testosterone is the principal hormone necessary for insuring the completion of
      normal spermatogenesis. However, its precise role in spermatid maturation is not
      clear. In hypophysectomized rats, testosterone can maintain spermiogenesis if
      replaced soon after surgery. Delaying treatment results in a reduction in the
      number of mature spermatids. In culture, testosterone and FSH are required to
      maximize spermatid attachment to binding-competent Sertoli cells. This binding
      event is an essential step in the process of spermiogenesis and is dependent on
      components of the Sertoli cell cytoskeleton. The present study was undertaken to
      determine the binding competency of Sertoli cells and their junctional
      interaction with spermatids in the hypophysectomized rat after immediate
      testosterone replacement and after delayed testosterone replacement.
      Hypophysectomized rats treated with immediate testosterone replacement had
      peripheral distribution of Sertoli cell f-actin and vinculin, structurally intact
      Sertoli ectoplasmic specializations facing step 8 spermatids, and daily sperm
      production similar to these parameters as observed in intact controls. In the
      delayed treatment group, these parameters were abnormal and were similar to those
      observed in the untreated hypophysectomized animals. The results suggest that
      testosterone can maintain binding competency of the Sertoli cell and normal
      Sertoli-spermatid junctional interaction but cannot restore them.

PMID- 8286582
TI  - Plasminogen activator activity in preovulatory follicles during the ovulatory
      cycle of the chicken.
AB  - The stages of follicular maturation of a preovulatory follicle in the chicken can
      be divided into an extended proliferative phase (prior to the LH surge) and a
      brief ovulatory phase (after the LH surge). There is evidence to suggest that
      plasminogen activator (PA) may play a role in follicular maturation and ovulation
      in the chicken. The objective of this study was to determine whether PA activity
      changes in the stigma (site of follicular rupture) and nonstigma regions of the
      theca layer, granulosa layer, and germinal disc region (germinal disc and
      adjacent granulosa cells; GDR) during the transition from the proliferative phase
      to the ovulatory phase and immediately before ovulation. The largest preovulatory
      follicle (F1) and the second-largest follicle (F2), which would have ovulated
      first and 26 h later, respectively, were collected at 8 h and 2 h before
      ovulation (before and after the LH surge, respectively), and at 0.5 h
      (immediately before ovulation). PA activity in the stigma region of the theca
      layer in the F1 and F2 follicles was very low at 8 h before ovulation (before the
      LH surge) and increased dramatically (9-fold) at 2 h before ovulation (after the
      LH surge). PA activity in the stigma region of the F1 follicles remained high as
      the follicles prepared to ovulate (0.5 h before ovulation), whereas in the stigma
      region of the less mature F2 follicles it decreased to a level similar to that
      measured 8 h before ovulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286581
TI  - Ovarian structures during the estrous cycle and early pregnancy in ewes.
AB  - The development of ovarian follicular and luteal structures during the estrous
      cycle and early pregnancy in ewes was examined. Ewes were treated with
      prostaglandin F2 alpha to induce estrus; they were placed with either two fertile
      or two vasectomized rams and observed for estrus twice daily. Beginning at estrus
      (Day 0), ovaries were scanned for CL and for follicles > or = 2 mm by transrectal
      ultrasonography daily for the first 25 days of pregnancy (PREG, n = 17 ewes) or
      until Day 8 of the second estrous cycle (CYC, n = 15 ewes). Jugular blood samples
      were collected at ultrasonography and on Days 30, 35, and 40 of gestation for RIA
      of progesterone and estradiol-17 beta. Total follicles (17.6 +/- 1.3), number of
      follicles > or = 4 mm in diameter (11.3 +/- 0.6), and number of follicles that
      became the largest during the first 16 days of pregnancy or the first estrous
      cycle (4.9 +/- 0.3) did not differ between PREG and CYC ewes. Number of newly
      detected follicles each day and difference in mean diameter between the largest
      two follicles and all other follicles were similar between PREG and CYC ewes
      until luteal regression. At that time, difference in diameter between the largest
      two follicles and all other follicles increased in CYC ewes in parallel with
      estradiol-17 beta in serum. Mean concentrations of progesterone in serum were
      higher in PREG than in CYC ewes (2.4 +/- 0.1 vs. 2.0 +/- 0.1 ng/ml; p < 0.05)
      before onset of luteal regression, but mean areas of CL did not differ.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8286583
TI  - A novel stage-specific differentiation antigen is expressed on mouse testicular
      germ cells during early meiotic prophase.
AB  - A murine cell surface antigen exhibiting stage-specific expression during
      spermatogenesis was detected with two monoclonal antibodies (mAbs), designated
      BC7 and CA12. In mouse testis, these mAbs recognized a small population of cells
      located near the periphery of seminiferous tubules at stages XII and I-VI, and
      these spermatogenic cells were identified as zygotene and early pachytene
      spermatocytes. Expression of the antigens was transient and was not detected in
      germ cells at more advanced stages of spermatogenesis such as late pachytene
      spermatocytes and round spermatids. Immunoprecipitation and immunoblotting
      studies showed that both mAbs CA12 and BC7 reacted with the same antigenic
      molecule, which had an estimated molecular mass of 95 kDa. CA12/BC7 antigen,
      detected in plasma membrane fraction, was a glycoprotein with sialic acid
      residues and had affinity with WGA lectin. Furthermore, intraperitoneal injection
      of mAb BC7 caused an apparent spermatogenic disturbance in prepubertal mice.
      These results suggested that CA12/BC7 antigen, a novel cell surface glycoprotein,
      is an essential molecule that plays an important role during early meiotic
      prophase of spermatogenesis.

PMID- 8286584
TI  - Localization of transforming growth factor alpha in the human placenta and
      decidua: role in trophoblast growth.
AB  - Transforming growth factor alpha (TGF alpha) is an important growth regulatory
      molecule, the location and function of which at the human fetomaternal interface
      remain to be determined. The present study examined the presence of TGF alpha in
      the human placenta, decidua, and fetal membranes throughout gestation (from a
      total of 29 subjects) as well as its functional role in the proliferation of
      first trimester trophoblasts. The peptide was localized immunocytochemically with
      a monoclonal anti-TGF alpha antibody (Ab) (MF9) on paraffin-embedded tissues via
      the avidin-biotin complex-peroxidase technique with diaminobenzidine (DAB) as the
      chromogen. Omission or TGF alpha absorption of the primary Ab served as negative
      controls. Specific (cytoplasmic) staining was noted in typical stromal-type
      decidual cells, including cells of the decidua basalis and parietalis and
      chorionic decidua, throughout gestation. Villous trophoblast cells
      (syncytiotrophoblast and to a minor extent cytotrophoblast) at all gestational
      ages as well as extravillous cytotrophoblast cells (intermediate and
      cytotrophoblastic shell) also showed specific cytoplasmic staining. Chorionic
      trophoblasts showed variable staining, and little or no immunoreactivity was seen
      in the amniocytes. Second-passage first trimester human trophoblast cells
      (characterized by their expression of cytokeratin as well as other markers) were
      cultured in the presence of TGF alpha or neutralizing anti-TGF alpha Ab (TAb-1)
      or no additive for 18 h prior to exposure to 3H-TdR for 6 h to measure 3H-TdR
      uptake. TGF alpha (0-100 ng/ml) caused a dose-dependent stimulation of
      proliferation, reaching a near plateau at 6-100 ng/ml to slightly more than
      double the basal level. The presence of anti-TGF alpha Ab alone (25
      micrograms/ml) did not significantly influence the proliferation of the cells,
      indicating the absence of significant endogenous TGF alpha in these cultures;
      however, the Ab was able to abolish the stimulatory function of exogenous TGF
      alpha. Exogenous TGF alpha also increased the number of trophoblast nuclei
      immunoreactive for proliferating cell nuclear antigen and reduced the incidence
      of multinucleate cells in culture. These results indicate that TGF alpha is
      present in the cells of the fetomaternal interface throughout human gestation and
      may function as a stimulator of trophoblastic growth in situ.

PMID- 8286585
TI  - Ovaries of ewes homozygous for the X-linked Inverdale gene (FecXI) are devoid of
      secondary and tertiary follicles but contain many abnormal structures.
AB  - Ewes homozygous (II) for the Inverdale prolificacy gene (FecXI) located on the X
      chromosome are infertile with "streak" ovaries. The aims of this study were to
      examine the ovarian morphology and plasma and tissue (or extracellular fluid)
      hormone concentrations in II ewes in comparison to control (++) animals. All II
      animals (n = 11) were found to contain no normal ovarian follicles beyond the
      primary stage of development despite their being similar in number of germ cells
      to the ++ ewes. The II animals had high plasma gonadotropin levels and
      undetectable estradiol and progesterone, and in addition 6 of 9 ewes had
      undetectable plasma inhibin concentrations. II ewes contained large numbers of
      oocyte-free follicles ("nodules") that were often found as clusters in the
      innermost regions of the cortex. In addition, 6 of 11 ewes contained abnormal
      luteal- or granulosa cell-like structures and other unusual formations. In three
      II animals the abnormal structures were visible on the ovarian surface, and the
      plasma inhibin concentrations in these ewes were significantly higher than in the
      ++ ewes (p < 0.05). Collectively these findings suggest that two copies of the
      FecXI mutation impair the resumption of growth of primordial follicles and may in
      some instances lead to the development of abnormal structures having a morphology
      consistent with that observed for ovarian tumors.

PMID- 8286586
TI  - In vivo induction of increased DNA ploidy of mouse cervicovaginal epithelium by
      neonatal estrogen treatment.
AB  - The purpose of this study was to test the hypothesis that exposure to natural
      estrogen early in the development of hormone-dependent tissue induces a change in
      nuclear DNA content. Female BALB/c mice were treated neonatally with daily s.c.
      injections of either 25 micrograms of 17 beta-estradiol (E2) in 0.02 ml of sesame
      oil (vehicle) or vehicle alone for 5 days. Treatment was begun either within 15 h
      of birth or 6 days after birth. One set each of 10-day-old E2-treated and control
      mice received s.c. pellet implants containing 15 mg of E2 and cholesterol (10% E2
      and 90% cholesterol), a second set received implants containing 25 mg of
      cholesterol alone, and a third set did not receive implants. Cervicovaginal
      tracts from intact BALB/c mice were examined histologically and by flow cytometry
      at 21, 40, 70, 180, or 240 days of age. The results obtained include several
      important findings: 1) neonatal E2 treatment in BALB/c mice causes an increase in
      nuclear DNA content in cervicovaginal epithelium; 2) short-term administration of
      secondary exogenous E2 reduces the latency period for the appearance of increased
      nuclear DNA content in neonatally E2-treated cervicovaginal epithelium; 3)
      increased nuclear DNA content can indicate abnormal cervicovaginal epithelium
      before histological abnormalities become evident; and 4) there is a sensitive
      period for neonatal E2 induction of increased nuclear DNA content in the
      cervicovaginal epithelium. These findings support other reports of the
      carcinogenic potential of estrogen in vivo. Therefore, increased DNA ploidy may
      be an important early detectable event in estrogen-induced carcinogenesis.

PMID- 8286587
TI  - Oxidative stress during the interaction of gametes.
AB  - Oxidative stress, commonly defined as a disturbance in the prooxidant and
      antioxidant levels, may be causatively involved in the etiology of defective
      sperm function. To mimic the physiological situation, in this study xenogeneic
      activators of the oxidative burst of sperm were excluded. In addition, transition
      metal-driven production of reactive oxygen species was avoided by chelation of
      Fenton catalysts. On average, 28 +/- 4 U of superoxide dismutase (SOD) and 375 +/
      105 mumol/L of sulfhydryls were found in normozoospermic ejaculates from 10
      healthy men. The in vitro inhibition of superoxide dismutase by
      diethyldithiocarbamate caused the rapid oxidation of seminal plasma sulfhydryls,
      suggesting a pivotal role for SOD in maintaining the antioxidant defense system
      and protecting against oxidant-induced injury. The production of superoxide by
      hamster sperm as well as hamster oocytes was examined by lucigenin-mediated
      chemiluminescence both prior to and following the addition of sperm to oocytes
      for in vitro fertilization. During fusion, the generation of superoxide from both
      sperm and oocytes was markedly suppressed. This inhibition was partially due to
      the superoxide dismutase released during gamete interactions.

PMID- 8286588
TI  - Granulosa-thecal cell interactions in the regulation of plasminogen activator
      activity during ovarian follicular development in the hen.
AB  - In the present studies, hen granulosa and thecal cells from the first (F1) and
      fourth (F4) largest and developing large white follicles (LWF) were cultured
      alone or cocultured, and plasminogen activator (PA) activity was determined. The
      PA of the cells (PAc) and the medium (PAm) was measured through use of the
      chromogenic substrate Val-Leu-Lys-p-nitroanilide, and the total PA (PAt) was
      calculated. The PA activity of cultured granulosa cells from all stages of
      follicular development increased with time of culture. Granulosa cell PAc and PAm
      activity differed with follicular development: the LWF granulosa cells had the
      highest levels of activity, the F4 had intermediate levels, and the F1 cells had
      the lowest. Thecal cell PA activity increased during culture but was unaffected
      by the stage of follicular development. Cocultures of granulosa and thecal cells
      from F1 follicles exhibited PA activity 2- to 3-fold higher than the sum of the
      activities of granulosa and thecal cells cultured alone. The PA activity of
      granulosa cells from LWF was not affected by coculture with thecal cells.
      Conditioned medium from thecal cells (TCCM) of all stages of follicular
      development stimulated PAc activity of granulosa cells from F1 and F4 follicles.
      Conditioned medium from thecal cells of F4 and LWF caused small inhibitory
      effects on the PAc activity of granulosa cells from LWF. Zymographic analysis of
      the PA activity of F1 granulosa cell cultures indicates that the enzyme activity
      is associated with a molecular mass of about 33 kDa, which is consistent with
      that of urokinase type PA. Thecal cell PA activity was unaffected by granulosa
      cell-conditioned medium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286589
TI  - Nuclear-cytoplasmic interactions during the first cell cycle of nuclear transfer
      reconstructed bovine embryos: implications for deoxyribonucleic acid replication
      and development.
AB  - The present study investigated the decay of maturation-promoting factor (MPF)
      activity in electrically activated in vitro-matured bovine oocytes and examined
      the influence of the cell cycle stage of both the donor nucleus and the recipient
      cytoplasm upon the morphology and DNA synthesis potential of the donor nucleus in
      reconstructed embryos. The decay of MPF activity was studied both biochemically
      in electrically activated in vitro-matured oocytes and by morphological
      examination of nuclear structure in reconstructed bovine embryos. As measured by
      H1 kinase activity in groups of 10 oocytes, the level of MPF declined rapidly to
      30 +/- 4% (of the maximum level in unactivated control oocytes) at 60 min and
      reached a basal level of 20 +/- 6% at 120 min. This level of activity was then
      maintained until at least 9 h postactivation. In contrast, when MPF activity was
      assayed by morphological examination of nuclei in individual reconstructed
      embryos, the decline in activity occurred over a period of 9 h postactivation.
      DNA synthesis of nuclei arrested at the G1/S border and in G2 phases of the cell
      cycle was examined in embryos reconstructed at the time of oocyte activation,
      i.e., when MPF levels were maximal, and by fusion 10 h postactivation, when no
      MPF activity could be detected. All nuclei transferred at the time of oocyte
      activation underwent nuclear envelope breakdown (NEBD) and subsequent DNA
      synthesis. However, when nuclei were transferred 10 h after activation, no NEBD
      was observed in any nuclei. Nuclei arrested at the G1/S border or nuclei in S
      phase when transferred in the absence of NEBD underwent DNA synthesis, while no
      DNA synthesis was observed in G2 nuclei transferred into this cytoplasmic
      environment. The results presented show that all nuclei, regardless of cell cycle
      stage, undergo DNA replication when transplanted into metaphase II (MeII)
      cytoplasts in which MPF activity is high. From these observations we would
      suggest that one factor that may contribute to the present low frequency of
      development of bovine nuclear transfer embryos is the ploidy of the reconstructed
      embryo after the first cell cycle. In order to maintain correct ploidy of the
      reconstructed embryo, only G1 nuclei should be transferred at the time of
      activation, when MPF levels are high. In contrast, when the integrity of the
      nuclear membrane is maintained by transfer at 10 h postactivation, when MPF
      activity is absent, the rereplication of G2 nuclei is prevented and correct
      ploidy of the reconstructed embryo may be maintained.

PMID- 8286590
TI  - Expression of c-fos in porcine endometrium during the estrous cycle and early
      pregnancy.
AB  - This study determined the pattern of expression of the c-fos oncogene in
      endometrium from pregnant and cyclic gilts. A transcript of the expected 2.2-kb
      size for the c-fos mRNA was detected in porcine endometrium from cyclic and
      pregnant gilts. Expression of endometrial c-fos mRNA was not different for Days
      0, 5, 10, 15, or 18 cyclic or pregnant gilts. However, expression of c-fos mRNA
      was greater on Day 12 of pregnancy compared to Day 12 of the estrous cycle.
      Furthermore, expression of c-fos mRNA was related to developmental stages when
      pig conceptuses secrete estradiol, the primary determinant for maternal
      recognition of pregnancy. Throughout the estrous cycle and early pregnancy,
      immunoreactive fos protein was localized to the glandular and surface epithelial
      cells as well as myometrial cells. Results of this study indicate that
      endometrial expression of c-fos mRNA increases on Day 12 of pregnancy, coinciding
      with the establishment of maternal recognition of pregnancy in pigs.

PMID- 8286592
TI  - Effects of injection of anti-luteinizing hormone (LH)-releasing hormone serum and
      anti-gonadotropin-releasing hormone-associated peptide serum into neonatal rats
      on LH and follicle-stimulating hormone cells.
AB  - Relatively little is known regarding the potential importance of LHRH and of
      gonadotropin-releasing hormone-associated peptide (GAP) on the postnatal
      development of gonadotrophs. We investigated the effects of administration of
      anti (A)-LHRH serum or A-GAP serum to neonatal rats on the development of LH and
      FSH immunoreactivity in anterior pituitary gland (APG) cells. Serum (sheep non
      immune [NSS], sheep A-LHRH, sheep A-LHRH/GAP [which bound LHRH and GAP], rabbit
      non-immune [NRS], or rabbit A-GAP) was injected s.c. into neonatal female and
      male rats on Days 1 and 3 or Days 1, 3, 5, and 7 after birth. Pups were killed on
      Day 5 or 9, two days after the last injection. The percentages of APG cells
      immunoreactive for LH or FSH increased from Day 1 to Day 5 and did not change
      between Days 5 and 9 in female pups treated with NSS or NRS. There was a trend
      for the percentages of LH and FSH cells to increase from Day 1 to Days 5 and 9 in
      male pups treated with NSS or NRS, but the increases were not statistically
      significant. In both females and males, treatment with antisera that recognized
      LHRH reduced the percentage of FSH cells on Day 5 and the percentages of LH and
      FSH cells on Day 9. Treatment with A-GAP was without effect in both sexes. There
      were similar percentages of LH and FSH cells in females and a lower percentage of
      FSH than of LH cells in males in the Day 5 and 9 controls.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8286591
TI  - Retinol differentially regulates male germ cell-associated kinase (mak) messenger
      ribonucleic acid expression during spermatogenesis.
AB  - Retinol down-regulates male germ cell-associated kinase (mak) transcripts during
      the spermatogonial proliferation phase of spermatogenesis. Mak transcripts of 2.6
      and 3.4 kb were detected in vitamin A-deficient germ cells, but decreased to
      undetectable levels shortly after retinol replacement to vitamin A-deficient
      rats. In contrast, mak seems to play a role in spermatocytes and round spermatids
      during meiotic and post-meiotic events. The 3.4-kb transcript initially appeared
      in pachytene spermatocytes and continued to increase in round spermatids; the
      level of the 2.6-kb transcript increased markedly only in round spermatids. These
      transcripts also exhibited stage-specificity in synchronized retinol-regenerated
      rat seminiferous tubules. Silver grains were intensely localized mainly in round
      spermatids in stages IV-VI of the spermatogenic cycle in normal tests after in
      situ hybridization. These results suggest that the mak gene in early germ cells
      responds to retinol in an opposite manner from the mak gene in spermatocytes or
      in round spermatids. The findings support the existence of two distinct pathways
      of retinol signaling in the testis that depend on the spatial localization and
      development ages of the individual germ cells.

PMID- 8286593
TI  - Expression of cellular retinol-binding protein and lecithin-retinol
      acyltransferase in developing rat testis.
AB  - Vitamin A deficiency in mammals results in the loss of germ cells on the
      adluminal side of the blood-testis barrier, suggesting a need for vitamin A that
      would be supplied by the surrounding Sertoli cells. Cellular retinol-binding
      protein (CRBP) and lecithin-retinol acyltransferase (LRAT) are two proteins found
      in Sertoli cells that are known to be involved in vitamin A trafficking. To
      clarify the role of these two proteins in the delivery of vitamin A to developing
      germ cells, we have examined changes in their cell-specific expression during the
      onset of puberty in the rat. In adult rats, Sertoli cell expression of CRBP
      varies with the cycle of the seminiferous epithelium. Here, we demonstrate that
      differences in the intensity of CRBP immunoreactivity are detectable in Sertoli
      cells of different tubules as early as postnatal Day 4, prior to the onset of
      meiosis. This indicates that variable expression of CRBP by Sertoli cells is
      established independently of late germ cells and may anticipate the cyclical
      variation seen in the adult. We further demonstrate that the specific activity of
      LRAT in rat testis increases tenfold between postnatal Days 20 and 35. This
      increase is attributable to the appearance of post-meiotic germ cells: the LRAT
      activity of microsomes prepared from a round spermatid-enriched cell fraction
      from post-pubertal rat testis could account for the majority of the LRAT activity
      observed in the whole testis. The presence of LRAT activity within adluminal germ
      cells suggests that they receive vitamin A as retinol and synthesize the retinyl
      esters that have been shown to be present in mature sperm.

PMID- 8286594
TI  - High-affinity binding of progesterone to the plasma membrane of Xenopus oocytes:
      characteristics of binding and hormonal and developmental control.
AB  - Progesterone induces maturation of the amphibian oocyte through its action on the
      plasma membrane. However, whether or not this action requires high-affinity
      binding to a specific receptor is unclear. In this study, the binding activity of
      progesterone was characterized in plasma membranes from whole ovaries or
      defolliculated oocytes of Xenopus laevis. Membrane-bound, radiolabeled
      progesterone was isolated by filtration of membrane suspensions and quantified by
      liquid scintillation. The association of progesterone to membrane preparations
      reached equilibrium within 15 min. Progesterone binding activity was directly
      proportional to the sample concentration, was significantly reduced by trypsin
      digestion, and was pH-dependent and temperature-sensitive. Also, binding activity
      was observed in membrane preparations from whole ovaries and defolliculated
      oocytes but not in those from somatic cells, indicating that progesterone binding
      is restricted to the oocyte membrane. Scatchard analysis indicated a single class
      of high-affinity (average KD, 10(-9) M), low-capacity (average concentration, 10(
      12) mol/mg protein) binding sites for progesterone in all oocyte membrane
      preparations tested. Progesterone binding activity was also detected in
      preparations from albino frog ovaries, indicating that the binding activity is
      not an artifact of melanin contamination. Competition studies showed the
      following order of affinities: progesterone > pregnenolone > 17 alpha, 20 beta,
      21-trihydroxy-4-pregnen-3-one > 11-deoxycorticosterone > 17 alpha, 20 beta
      dihydroxy-4-pregnen-3-one > 11-deoxycortisol > estradiol > R5020 > corticosterone
      > aldosterone > cortisol > androstenedione > ouabain.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8286595
TI  - Immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase in the
      rat ovary during follicular development and atresia.
AB  - In the adult ovary, cohorts of growing follicles are continuously generated, from
      which dominant follicles are selected during each estrous cycle. To compensate
      for the rapid proliferation of follicular cells in the growing pool of follicles,
      follicles are eliminated by atresia, thereby maintaining ovarian tissue mass.
      Estrogens and androgens have been implicated as intraovarian regulators of
      follicular growth and atresia, suggesting that the fate of an individual follicle
      to develop to the preovulatory stage or to undergo atresia is associated with
      distinct profiles of steroid production. We therefore have localized 3 beta
      hydroxysteroid dehydrogenase (3 beta-HSD), an enzyme required for the
      biosynthesis of all major steroid hormones, in ovaries of immature and adult rats
      during follicular development, atresia, and corpus luteum formation. The pattern
      of immunostaining for 3 beta-HSD remained constant in the interstitial cell
      compartment and was not affected by the age of the rats nor the stage of the
      estrous cycle. As thecal cells differentiated from the surrounding stroma and
      restructured around the secondary follicle, they expressed intense staining for 3
      beta-HSD. This staining persisted in preantral, antral, and preovulatory
      follicles. Granulosa cells in primary, secondary, and antral follicles did not
      contain detectable levels of 3 beta-HSD and did not stain positively until the
      follicle reached the preovulatory stage of development. A novel finding presented
      in this paper is that 3 beta-HSD persisted in the thecal cells of follicles
      throughout the entire process of atresia, suggesting that during atresia the
      potential for the synthesis of androgens is retained.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8286596
TI  - Identification of the predominant proteins in uterine fluids of unilaterally
      pregnant ewes that inhibit lymphocyte proliferation.
AB  - Uterine fluid from unilaterally pregnant ewes contains activity inhibitory to
      lymphocyte proliferation. The molecules responsible for this activity may thereby
      regulate uterine immune responses during pregnancy. The purpose of the experiment
      described here was to identify the major protein in uterine fluid responsible for
      this activity. When uterine fluid was fractionated by a combination of cation
      exchange chromatography, gel filtration, and lectin affinity chromatography, the
      majority of the lymphocyte activity co-migrated with a pair of proteins
      previously identified as related, serpin-like glycoproteins. Together, this pair
      of proteins, called the uterine milk proteins (UTM-proteins), are the predominant
      endometrial secretory protein produced under the influence of progesterone.
      Preparations of uterine protein highly enriched for the UTM-proteins inhibited
      lymphocyte proliferation induced by phytohemagglutinin, concanavalin A, and mixed
      lymphocyte reactions but did not inhibit proliferation induced by pokeweed
      mitogen. In some experiments, UTM-proteins also reduced viability of cultured
      lymphocytes. Another previously described lymphocyte-inhibitory factor,
      megasuppressin, was also observed. Megasuppressin, which eluted at an apparent
      molecular weight of greater than 4 x 10(6) even after treatment with urea,
      guanidine-HCl, and beta-mercaptoethanol, was a more potent inhibitor of
      lymphocyte proliferation than UTM-proteins. Megasuppressin is not very abundant,
      however, and probably is responsible for only a small fraction of the lymphocyte
      inhibitory activity in uterine fluid. The majority of lymphocyte-inhibitory
      activity is caused by the UTM-proteins or by a molecule that co-purifies in trace
      amounts with UTM-proteins.

PMID- 8286597
TI  - Human myometrial smooth muscle cells are novel targets of direct regulation by
      human chorionic gonadotropin.
AB  - Human myometrium contains receptors for hCG/human LH (hLH). This suggested the
      possibility that hCG and hLH might regulate human myometrium, which has not
      previously been considered a direct target of gonadotropin regulation. To
      investigate such a possibility, highly pure and viable smooth muscle cells were
      isolated from nonpregnant human myometrium and cultured as monolayers. The cells
      contained hCG/LH receptor mRNA transcripts and a 50-kDa immunoreactive protein
      that can bind 125I-hCG in a ligand-specific manner. The presence of hCG during
      culture resulted in a significant increase of myometrial smooth muscle cell
      density. The hCG effect was time- and concentration-dependent and was mimicked by
      hLH but not by human FSH or human FSH or human thyroid-stimulating hormone. Human
      CG also greatly increased the size of a subpopulation of myometrial smooth muscle
      cells without affecting their chromosomal ploidy. Antibodies to hCG/LH receptors
      and hCG blocked hCG effects. Human prolactin and growth hormone, which do not
      bind to hCG/LH receptors, also increased the myometrial smooth muscle cell
      density. A protein kinase A inhibitor (H-89) blocked hCG response whereas
      calphostin (a protein kinase C inhibitor) and lavendustin A (a tyrosine kinase
      inhibitor) had no effect on hCG response, suggesting that a cAMP/protein kinase A
      signaling mechanism is involved in hCG action. Eicosanoids from cyclooxygenase
      and 5-lipoxygenase pathways of arachidonic acid metabolism are probably not
      involved, because the inhibitors of these enzymes had no effect on hCG response.
      While progesterone and estradiol could not mimic or modify hCG action, epidermal
      growth factor did mimic hCG in increasing myometrial smooth muscle cell
      density.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286598
TI  - Cytogenetic evaluation of ova from pubertal and third-estrous gilts.
AB  - Cytogenetic characteristics of ova surgically recovered from 19 first-estrous
      (pubertal) gilts were compared with those from 24 third-estrous gilts. Mean
      percentage recovery of ova was 82.1 +/- 2.9%. A total of 159 and 203 ova from
      first- and third-estrous gilts, respectively, were evaluated. Gilts at first and
      third estrus ovulated more mature ova (metaphase I-II chromosomes visible) than
      immature ova (germinal vesicle stage through prometaphase stage), but the
      percentage of immature ova in gilts at first estrus was greater than in those at
      third estrus (33.1 vs. 24.1%, p < 0.06). Percentage of mature ova with a normal
      haploid complement of chromosomes was similar in gilts at first and at third
      estrus (52.7 vs. 47.5%, p > 0.10). Percentage of hyperploid ova did not differ
      between first- and third-estrous gilts (10.8 vs. 5.9%, respectively); however,
      estimated frequency of nondisjunction appeared greater for gilts at first than at
      third estrus (21.6 vs. 11.9%, p < 0.10). These data suggest that ova of first
      estrous gilts are inferior in quality compared to those of cyclic gilts.

PMID- 8286599
TI  - Developmental expression of activin/inhibin beta A, beta B, and alpha subunits,
      and activin receptor-IIB genes in preimplantation mouse embryos.
AB  - We demonstrated previously that activin A released the two-cell block of mouse
      embryos cultured in vitro and stimulated early embryonic development. We then
      confirmed immunohistochemically the presence of the beta A, beta B, and alpha
      subunits in early embryos together with the oviductal epithelium facing those
      embryos. The results of in situ hybridization and reverse-transcription
      polymerase chain reaction here show the presence of mRNA transcripts for
      activin/inhibin beta A, beta B subunits in the ovary, oviduct, unfertilized egg,
      and embryo at the early preimplantation stage. However, the mRNA of the inhibin
      alpha subunit was not expressed in any of these. Considering our previous
      demonstration of the immunoreactive beta A, and beta B subunits of
      activin/inhibin polypeptides in the cytoplasm of 1- and 2-cell embryos, we
      suggest that activins appearing in the oviduct and in embryos are not only
      transferred from the follicular fluids, but produced by the oviduct, oocytes, and
      embryos themselves. Since the mRNA of the inhibin alpha subunit was absent at
      those stages, the beta A and beta B subunits may not exist as the inhibin
      molecule. The mRNA of activin receptor-IIB was detected in the ovary, in embryos
      at the 1-cell and the 8-cell/morula stages, and also in the unfertilized egg,
      although to a lesser extent, but not in the oviduct or in the 2-cell-stage embryo
      either in vivo or cultured in vitro. These results suggest that activin is
      physiologically involved in the process of early development of mouse embryos.

PMID- 8286600
TI  - Maintenance of sexual function with testosterone in the gonadotropin-releasing
      hormone-immunized hypogonadotropic infertile male rat.
AB  - We have previously shown that active immunization against GnRH in the mature male
      rat can predictably produce hypogonadotropic hypogonadism and azoospermia and,
      further, that normospermia and normal fertility can be restored by testosterone
      (T) administration alone. The objective of this study was to explore the
      hypothesis that GnRH-immunized azoospermic rats could be supplemented with T
      doses sufficient to restore sexual behavior, but insufficient to support adequate
      spermatogenesis or to allow restoration of fertility. Adult male rats of proven
      fertility were immunized against GnRH and supplemented with 2-, 4-, or 8-cm T
      implants or with empty implants. Eight weeks later, fertility was evaluated;
      concentrations of serum T, LH, FSH, growth hormone (GH), prolactin (PRL), and
      thyroid-stimulating hormone (TSH) were determined; sperm number was obtained from
      the testis; and weights of androgen-dependent organs were measured. GnRH
      immunization and T supplementation resulted in restoration of organ weights and
      of fertility in a dose-dependent manner. GnRH immunization with or without T
      supplementation resulted in the absence of circulating gonadotropins, but had no
      effect on serum GH, PRL, or TSH levels. Whereas all control animals were fertile,
      rats that received either empty or 2-cm T implants were completely infertile.
      Rats that received 4-cm or 8-cm T implants were fertile in 60% and 100% of cases,
      respectively. Sexual behavior of rats with empty and with 2-cm T implants was
      compared at 10-18 wk after immunization with GnRH. GnRH-immunized rats given
      empty implants displayed negligible sexual activity, but those with 2-cm T
      implants displayed sexual activity equivalent to that of untreated controls
      despite complete infertility.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286601
TI  - Mechanisms of action for an androgen-mediated autoregulatory process in rat
      thecal-interstitial cells.
AB  - In rat thecal-interstitial cells (TIC), treatment with the synthetic androgen
      mibolerone has led to the documentation of an autoregulatory process for androgen
      production. In the present study, accumulated evidence has provided insight into
      the mechanisms of mibolerone action that control this process. Investigations
      using the nonsteroidal antiandrogen hydroxyflutamide were conducted to
      characterize mibolerone's mode of action. Hydroxyflutamide had differential
      effects on hCG action, the 1-microM dose stimulating hCG-induced androsterone
      synthesis by 27% and the 10-microM concentration decreasing the androgen levels
      by 84%. In addition, treatment with 1 microM hydroxyflutamide was effective in
      partially reversing the inhibitory action of mibolerone on hCG-stimulated
      androsterone production. Thus, the data indicated that mibolerone's mode of
      action may be mediated, at least in part, via the androgen receptor. The
      possibility that mibolerone had multiple sites of action prompted studies on the
      effectiveness of this androgen to alter various signaling pathways. Treatment
      with increasing concentrations (0.01-100 nM) of the phorbol ester 12-0
      tetradecanoylphorbol 13-acetate (TPA), which activates protein kinase C, resulted
      in a 75% decrease in hCG-stimulated androgen production at a dose of 100 nM TPA.
      Treatment with mibolerone (100 nM) was unable to alter the action of TPA on
      androgen synthesis when doses of 1 and 10 nM TPA were employed. It was also found
      that Ca2+ can serve as a mediator of mibolerone action. Treatment with a 0.01
      microM dose of A23187, a Ca2+ ionophore known to increase intracellular Ca2+, was
      ineffective in altering hCG-stimulated androsterone synthesis. The concurrent
      treatment of mibolerone (100 nM) and A23187 (0.01 microM) resulted in the
      potentiation of mibolerone's inhibitory effects on hCG-stimulated androgen
      production, thereby suggesting that mibolerone can stimulate Ca2+ influx.
      Additional studies revealed that the administration of a 1-microM dose of the L
      type Ca2+ channel blocker verapamil to TIC cultures was able to partially block
      the inhibitory effect of mibolerone on androgen synthesis. Evidence for an
      additional site of mibolerone action was revealed through an analysis of the mRNA
      levels of P450scc and P450(17) alpha enzymes. Although hCG and insulin-like
      growth factor I treatment resulted in 20- and 32-fold increases in the amount of
      P450scc and P450(17) alpha mRNA, respectively, the addition of mibolerone (100
      nM) reduced only P450(17) alpha mRNA levels by 91%. Overall, the evidence
      indicates that mibolerone has multiple sites of action in exerting its regulatory
      effect on androgen synthesis.

PMID- 8286602
TI  - Fertility-associated proteins in Holstein bull seminal plasma.
AB  - This study was undertaken to determine whether bovine seminal plasma contained
      protein markers associated with bull fertility, and whether these markers were of
      value in predicting bull fertility. Seminal plasma was obtained from 35 Holstein
      bulls of known fertility. Two-dimensional PAGE of seminal plasma samples
      indicated that two proteins (26 kDa, pI 6.2; 55 kDa, pI 4.5) predominated in
      higher-fertility bulls, and two proteins (16 kDa, pI 4.1; 16 kDa, pI 6.7)
      predominated in lower-fertility bulls. Densitometry data for these proteins in
      individual samples were combined for bulls grouped by fertility level. Average
      density of the 26-kDa protein was significantly greater in seminal plasma of high
      fertility bulls, and high-fertility seminal plasma also contained more of the 55
      kDa protein than that of average- and below average-fertility bulls. Below
      average- and low-fertility bull seminal plasma had significantly more of both 16
      kDa proteins than that of average- and high-fertility bulls. A regression model
      was developed to predict bull fertility using the four fertility-associated
      protein densities. A plot of actual bull fertility versus that calculated by this
      model was linear and positively correlated (r = 0.89). These findings indicate
      that bull seminal plasma contains fertility-associated proteins that are
      predictive of bull fertility.

PMID- 8286603
TI  - Enhanced ovarian inhibin subunit gene expression in aging rats is due to chronic
      anovulation.
AB  - The persistent-estrous (PE) state in aging rats, characterized by a lack of
      ovulation and absence of estrous cycles, is associated with enhanced inhibin
      alpha and beta A subunit mRNA expression in the ovaries. It has been shown that
      the PE state can be interrupted by successive treatments with a progesterone
      implant (P-implant) and that estrous cycles can be transiently restored after
      implant removal. The present study examined whether restoration of estrous cycles
      in PE rats could reverse the altered ovarian inhibin alpha and beta A subunit
      gene expression. PE rats were treated with subcutaneous P-implants for 6 wk.
      After implant removal, the return of estrous cyclicity was confirmed by
      characteristic cyclic changes in vaginal cytology. Ovaries collected from the P
      implant-treated animals at 1100 h on diestrus Day 2 or proestrus showed
      significantly decreased levels of both inhibin alpha and beta A subunit mRNAs
      compared to those of PE controls and young cyclic females. In situ hybridization
      revealed that the decreased inhibin alpha subunit mRNA after P-implants was due
      to decreased gene expression in the granulosa cells of large preovulatory
      follicles and to a compete absence of gene expression in large, cystic follicles
      devoid of granulosa cells and oocytes. In addition, inhibin alpha subunit mRNA
      was expressed in the newly developed follicles after implant removal. The beta A
      subunit mRNA was detected only in maturing follicles, not in newly developing
      follicles or in the large cystic follicles. The patterns of ovarian inhibin alpha
      and beta A subunit gene expression mimicked those of cyclic animals. These data
      indicate that loss of estrous cycles in aging rats results in an overexpression
      of inhibin alpha and beta A mRNAs in large and anovulatory follicles and that
      reinstatement of ovarian cycles in aged rats restores inhibin gene expression to
      normal levels.

PMID- 8286604
TI  - Surface and surface-to-volume relationships of the Sertoli cell during the cycle
      of the seminiferous epithelium in the rat.
AB  - The surface relationships of the Sertoli cell and the surface relationships of
      the Sertoli cell in comparison to the changing volumes of developing germ cells
      were studied using morphometric techniques at periods representing nine groupings
      of the fourteen defined periods in the cycle of the seminiferous epithelium of
      the adult rat. No cyclic variation in the total Sertoli plasma membrane surface
      area was noted. Cyclic variations were noted in the area of the Sertoli cell
      surface that faces the basal compartment germ cells, but not the basal lamina. No
      cyclic variations were noted in the amount of contact of the Sertoli cells with
      each other at the level of the Sertoli cell barrier. However, when areas in the
      adluminal compartment were studied, significantly less Sertoli-Sertoli contact
      was seen in stages V through VII than in other stages with the exception of
      stages II-IV. Surface contact of germ cells with Sertoli cells increased
      progressively as germ cells entered the intermediate compartment and progressed
      to late spermatids. However, a calculation of the surface-to-volume ratio showed
      that surface increases of the Sertoli cell in relation to the volume of germ
      cells were greatest in elongating spermatids past step 12 of spermiogenesis. The
      area in which Sertoli ectoplasmic specializations faced germ cells was determined
      throughout spermatogenesis, and these data demonstrated that the first appearance
      of ectoplasmic specialization was at the mid-pachytene phase. They also showed
      that stage VIII was a period when ectoplasmic specialization loss from the cell
      surface was evident. Less Sertoli ectoplasmic specialization face step 8 and step
      19 spermatids than comparable germ cell types at other stages. In addition to
      Sertoli cell surface area changes during the cycle, volumes of individual germ
      cell types were determined for the first time. The data presented allow an
      objective understanding of the complex structure and relationships of the Sertoli
      cell and provide a basis for understanding functional changes and interpreting
      biochemical data.

PMID- 8286605
TI  - Spermatogenesis is accelerated in the immature Djungarian and Chinese hamster and
      rat.
AB  - The rate of progression of spermatogenesis was studied in immature Djungarian and
      Chinese hamsters and Wistar rats by scoring the most advanced cell types present
      at various ages after birth. From 15 days of age onward, the most advanced cell
      types in the Djungarian hamsters were formed at a rate compatible with the
      duration of the spermatogenic cycle in adult animals, i.e., 7.9 days. However, in
      Djungarian hamsters up to 15 days of age, the rate of spermatogenic development
      was accelerated. The estimated duration of the spermatogenic cycle ranged between
      5.0 and 5.3 days. In the rats, spermatogenesis also was accelerated during the
      first 15 days of life, with an estimated duration of the seminiferous cycle of
      4.5-5.3 days. From 15 days of age onward, the rate of progression was strongly
      reduced, being compatible with the adult value of 12.8 days. In the Chinese
      hamsters, a similar change in the rate of spermatogenesis occurred at 25 days.
      Before this age, spermatogenesis proceeded with an estimated duration of the
      cycle of 8.8-9.2 days. From 25 days onward, spermatogenesis advanced much more
      slowly, at a rate compatible with the adult value of 17.0 days. Despite the
      strong reduction in the rate of spermatogenic progression in the three species,
      the cellular associations in the stages of spermatogenesis were not affected. In
      the three species, the clear reduction in the rate of spermatogenic progression
      correlated with the process of testicular descent, with the appearance of
      pachytene spermatocytes associated with preleptotene spermatocytes, and with the
      onset of tubular lumen formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286606
TI  - Characterization of a sperm-specific monoclonal antibody and isolation of 95
      kilodalton fertilization antigen-2 from human sperm.
AB  - Monoclonal antibodies (mAbs) were raised in mice against human sperm. Of the
      eight hybridomas secreting mAbs that react with human sperm, one, the Vic-1
      antibody, was selected for detailed analysis because of its high degree of tissue
      specificity. The Vic-1 antibody was of the IgG1 subclass and demonstrated binding
      predominantly with the acrosomal regions of viable but not methanol-fixed
      noncapacitated and capacitated human sperm cells. It also reacted with the
      acrosomal and mid-piece regions of viable capacitated as well as noncapacitated
      murine sperm, but not with methanol-fixed murine sperm. The Vic-1 antibody was
      germ-cell specific as it did not react with any human somatic cell, tissue, or
      secretion examined including seminal plasma. The Vic-1 antibody significantly (p
      = 0.0006) inhibited human sperm penetration of zona-free hamster oocytes in a
      concentration-dependent manner; at 15 g% concentration it almost completely
      blocked sperm penetration. The antibody significantly reduced the acrosome
      reaction and the release of acrosin activity in human sperm cells. There was no
      effect of the Vic-1 antibody on percentage of motile sperm, although it
      significantly affected motility characteristics such as linearity, amplitude of
      lateral head displacement, and beat frequency; motility parameters involved in
      the hyperactivation phenomenon related to capacitation and the acrosome reaction.
      The Vic-1 antibody recognized a predominant antigen of 95 kDa, designated
      fertilization antigen-2 (FA-2), in Western blot and immunoprecipitation
      procedures using human sperm preparations. The FA-2 antigen was isolated from
      human sperm preparations by using an immunoaffinity column containing the Vic-1
      antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286607
TI  - Expression of laminin and nidogen genes during the postimplantation development
      of the mouse placenta.
AB  - The expression patterns of laminin A, B1, B2, and nidogen genes were identified
      by in situ hybridization in postimplantation mouse extraembryonic tissues and
      maternal decidua during the period when the chorioallantoic placenta is
      established. Laminin and nidogen genes were not coordinately expressed either in
      the decidua or in trophoblast cells, indicating that these genes are regulated
      independently in these cell types during the establishment of the placenta.
      Laminin A mRNA was absent from the decidua except in the outer layer of cells
      adjacent to the myometrium and in the central decidual zone adjacent to the
      remnant of the uterine epithelium on Day 9. At this stage laminin B1, B2, and
      nidogen genes were strongly expressed in these cells and also in other regions of
      the decidua. Laminin B1 mRNA was present at higher levels in the decidua
      capsularis than in the decidua basalis, while nidogen mRNA showed highest
      expression in the decidua basalis. Laminin B2 mRNA was produced uniformly
      throughout the decidua at very high levels, suggesting that laminin B2 chains may
      be an important component of the decidual matrix. By Day 11, the nidogen gene was
      expressed only in endothelial cells lining the maternal blood spaces within the
      decidua. Laminin B1 and nidogen mRNAs were found at high levels within
      trophoblast giant cells at all stages, while laminin A mRNA was detected in
      trophoblast giant cells at later stages and laminin B2 mRNA was not produced in
      high levels by these cells. The patterns of gene expression show a very high
      degree of regional specialization, suggesting that the extracellular matrices in
      different regions of the decidua and extraembryonic membranes are likely to be
      composed of quite different ratios of laminin and nidogen polypeptides.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8286608
TI  - Suppression of the hypothalamic-pituitary-ovarian axis in normal women by
      glucocorticoids.
AB  - To determine whether cortisol has an effect on hypothalamic-pituitary-gonadal
      function, we studied 11 eumenorrheic women in the early follicular phase of
      consecutive menstrual cycles by performing daytime 10-min blood sampling, one
      before and one during hydrocortisone administration. Daily blood sampling for
      gonadotropins and sex steroids was also performed. LH pulsations were determined
      by modification of a widely used threshold method and compared by paired t
      testing. The LH interpulse interval was significantly prolonged (95 +/- 5 to 119
      +/- 14 min; p = 0.001), and the mean LH pulse amplitude remained unchanged (1.3
      +/- 0.1 and 1.5 +/- 0.2 mIU/ml) with glucocorticoid exposure. Mean estradiol was
      not altered (46 +/- 5 and 43 +/- 3 pg/ml), but mean LH and FSH from pooled serum
      aliquots were slightly but significantly reduced (2.6 +/- 0.2 to 2.2 +/- 0.2, 5.5
      +/- 0.4 to 4.5 +/- 0.3 mIU/ml; p = 0.004, 0.012, respectively). Mean progesterone
      levels were also decreased (0.8 +/- 0.3 to 0.5 +/- 0.2 ng/ml; p = 0.011) in the
      presence of exogenous glucocorticoid. Twenty-four-hour urinary free cortisol
      levels confirmed a substantial increase in free cortisol excretion (74 +/- 10 to
      305 +/- 50 micrograms/day; p = 0.001). These results demonstrate that cortisol
      can slow LH pulse frequency and, by inference, hypothalamic GnRH secretion, in a
      manner that appears independent of corticotropin releasing factor. Excess
      cortisol alone may therefore play a role in the development of stress-associated
      menstrual disturbances.

PMID- 8286609
TI  - Dynamic changes of gap junctions and cytoskeleton during in vitro culture of
      cattle oocyte cumulus complexes.
AB  - Changes in cell-to-cell contact and distribution of cytoskeletal components were
      investigated during in vitro culture of cattle oocyte cumulus complexes (OCC).
      Freeze-fracture analysis (FF), microinjections of the fluorescent dye Lucifer
      Yellow (LY), immunofluorescence, and ultrastructural immunocytochemistry were
      used. The cumulus cells (CC) remained in close contact via gap junctions (GJ)
      constituted of connexin43 (Cx43) during the entire culture time. Whereas the GJ
      decreased in diameter after 24 h of culture, their number was still substantially
      great at that time. The Cx43-positive GJ, localized between corona radiata cell
      projections and oolemma, disappeared after 6 h of culture. Concomitantly, the OCC
      lost the ability to transfer LY from cumulus to oocyte, and connexin32 (Cx32)
      became detectable in the oocytes. Both the changes in corona-oocyte coupling and
      cumulus expansion were preceded by the redistribution of F-actin in cytoplasm of
      CC. These data indicate that functional GJ linked the CC until the second meiotic
      arrest. However, the removal of Cx43-positive GJ interconnecting cytoplasmic
      projections of corona radiata cells with the oocyte was temporally correlated
      with germinal vesicle breakdown. The present results suggest the pivotal role of
      the cytoskeleton (F-actin) in cumulus expansion.

PMID- 8286610
TI  - Effects of glucose and fructose on fertilization, cleavage, and viability of
      mouse embryos in vitro.
AB  - In this study we examined the role of glucose, and the use of fructose as a
      replacement, in embryo culture medium. Three embryo culture media were used: a
      routine embryo culture medium (M16), M16 without glucose (M16-G) and M16-G
      supplemented with fructose (M16F-G). Their effect on fertilization, rate of
      cleavage, and embryo viability were examined in both an outbred (OF1) and an
      inbred (C57Bl) mouse strain. Of the three media, only M16 was found to support
      fertilization. In vitro-fertilized embryos from OF1 oocytes and C57Bl oocytes and
      OF1 sperm were placed in the different media at the early 2-cell stage. In 65% of
      OF1 embryos cultured in M16, development was blocked at the 2-cell stage, whereas
      in M16-G and M16F-G embryos, only 22% and 32%, respectively, were blocked. M16F-G
      medium also produced morulae and blastocysts with higher cell numbers than M16-G.
      In vitro-fertilized C57Bl 2-cell embryos cultured in M16 displayed retarded
      cleavage to the 4-cell stage compared to embryos cultured in M16-G and M16F-G. In
      contrast, the morulae and blastocyst cell numbers were significantly lower in M16
      G compared to M16 and M16F-G. The viability of morulae and blastocysts obtained
      from OF1 and C57Bl embryos cultured in M16-G and M16F-G was lower compared to
      control C57Bl morulae and blastocysts cultured in M16. The results show that
      although morphologically normal embryos could be obtained in M16-G and M16F-G,
      inherent anomalies existed that limited viability.

PMID- 8286611
TI  - Expression and regulation of cytochrome P450 17 alpha-hydroxylase messenger
      ribonucleic acid levels and androstenedione production in hen granulosa cells.
AB  - Studies were conducted to evaluate the expression and regulation of cytochrome
      P450 17 alpha-hydroxylase (P450 17 alpha-OH) mRNA levels and androstenedione
      production in 6-8-mm-diameter follicle granulosa cells from the domestic hen.
      Although P450 17 alpha-OH mRNA was detected within granulosa cells from follicles
      at all stages of development (3-12-mm and preovulatory follicles), 8-12-fold
      higher levels were found in small, less developed follicles (3-12 mm in diameter)
      compared to the three largest follicles within the preovulatory hierarchy (F3 to
      F1 follicles). By comparison, P450 17 alpha-OH mRNA levels were 25-89-fold higher
      in theca tissue compared to the granulosa layer at comparable stages of
      development. Despite detection of P450 17 alpha-OH mRNA in granulosa cells from 6
      8-mm follicles, androstenedione production was low to nondetectable when cells
      were cultured in the presence of exogenous progesterone (10 ng/ml). Treatment
      with FSH increased levels of P450 17 alpha-OH mRNA (by 6-fold after 16 h of
      treatment) and induced androstenedione production in cultured granulosa cells;
      these actions were mimicked by the cAMP analog, 8-bromo-cAMP. By contrast,
      addition of the growth factors transforming growth factor alpha (TGF alpha),
      epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF)
      completely suppressed the stimulatory effects of FSH on both mRNA levels and
      androstenedione production, while insulin-like growth factor I (IGF-I) inhibited
      only androstenedione production. We conclude that in the granulosa layer of
      developing (< or = 12 mm) hen follicles the expression of P450 17 alpha-OH mRNA
      does not directly reflect P450 17 alpha-OH enzyme activity. Moreover, P450 17
      alpha-OH mRNA levels dramatically decrease in granulosa cells from preovulatory
      (compared to developing) follicles, and in the theca layer from the F1
      preovulatory follicle (compared to remaining follicles). It is proposed that FSH
      initiates P450 17 alpha-OH enzyme activity (and perhaps to a lesser extent
      regulates mRNA levels) at the time a follicle is recruited into the preovulatory
      hierarchy, and that this action is mediated, at least in part, by the adenylyl
      cyclase/cAMP second messenger pathway. On the other hand, growth factors
      (including TGF alpha, EGF, bFGF, and possibly IGF-I) may act to prevent premature
      expression of P450 17 alpha-OH activity in the granulosa layer of follicles that
      have yet to enter the rapid growth phase of follicle development.

PMID- 8286612
TI  - Reproductive condition, glomerular adenosine diphosphatase activity, and platelet
      aggregation in the rat: effect of endotoxin.
AB  - In experiment A, the activity of the glomerular antithrombotic enzyme adenosine
      diphosphatase (ADPase) and the sensitivity of this enzyme for endotoxin (1.0
      microgram/kg BW) in various reproductive conditions of female rats were studied
      through use of enzyme histochemical methods. In experiment B, the effect of this
      dose of endotoxin on the thrombotic tendency of the glomeruli in pregnant (Pr)
      and pseudopregnant (PSP) rats was studied by means of ex vivo alternate perfusion
      of the kidneys with human platelets and adenosine diphosphate (ADP). In
      experiment A, cyclic (C), ovariectomized (OVX), Pr, and PSP rats were infused
      with endotoxin or saline. Three days later (for Pr and PSP rats, Day 8), animals
      were killed. In intact rats (C, Pr, PSP), the activity of glomerular ADPase was
      the same; however, the activity decreased after OVX. Endotoxin decreased the
      activity of glomerular ADPase in Pr rats only. In endotoxin-treated Pr rats,
      spontaneously formed platelet microaggregates were present in a few glomeruli; in
      glomeruli of the other groups, microaggregates were not observed. Platelet
      microaggregates were also present in the venous microvasculature of endotoxin
      treated Pr rats and, to a lesser extent, in that of other groups, while saline
      treated OVX rats were negative in this respect. In experiment B, Pr and PSP rats
      were treated as in experiment A; ex vivo kidney perfusion was performed on Day 8.
      Immediately after perfusion, rats were killed. Only Pr endotoxin-treated rats
      exhibited significantly increased intraglomerular platelet aggregation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8286613
TI  - Luminescence luteinizing hormone/choriogonadotropin (LH/CG) bioassay: measurement
      of serum bioactive LH/CG during early pregnancy in human and macaque.
AB  - Because of the microheterogeneities of gonadotropins, measurement of
      immunoreactivity of these glycoproteins does not necessarily reflect changes in
      their bioactivity. In addition, LH bioactivities in human samples analyzed by a
      rodent LH bioassay have been discordant with findings based on human granulosa
      luteal cells. We have isolated a human LH/choriogonadotropin (CG) receptor cDNA
      and expressed the recombinant protein. Using 293 cells permanently transfected
      with the human LH receptor cDNA and a luciferase reporter gene driven by a cAMP
      dependent promoter, we have developed a luminescence LH/CG bioassay. After cells
      were treated with human LH or CG for 20 h, luciferase activity was measured
      through use of a luminometer. Luciferase activity in the cells was increased in a
      dose-dependent manner. In contrast, treatment with FSH, thyroid-stimulating
      hormone, prolactin, growth hormone, adrenocorticotropin, insulin, prostaglandins,
      and several neurotransmitters had no effect. Because treatment with basic
      fibroblast growth factor (bFGF) caused significant increases in basal luciferase
      activity, a fixed amount of bFGF was included in all reactions. Incubation with
      0.1 to 30 microliters serum from women during different physiological states
      stimulated the luciferase activity in parallel with the hCG standard curve. In 4
      conception cycles, bioactive LH/hCG levels began to increase 2 wk after the
      midcycle LH surge, followed by a logarithmic increase from 22 days on. Due to the
      lack of a homologous RIA for measuring CG levels in monkeys, we analyzed serum
      bioactive monkey CG (mCG) in macaque during early pregnancy. Bioactive mCG was
      detected about 12 days after the midcycle LH surge and fertile mating and
      persisted until Days 21-23, followed by a decline.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8286614
TI  - Overexpression of uteroferrin, a lysosomal acid phosphatase found in porcine
      uterine secretions, results in its high rate of secretion from transfected
      fibroblasts.
AB  - Lysosomal enzymes can, under certain circumstances, be secreted in large amounts.
      One example is uteroferrin (Uf), an iron-containing, purple-colored acid
      phosphatase secreted by the uterus of the pig during pregnancy. Uf is identical
      to the intracellular tartrate-resistant acid phosphatase of pig spleen, yet is
      the major protein component of uterine secretions. To investigate possible
      regulatory mechanisms that might direct Uf along a secretory pathway, we
      expressed Uf in Chinese hamster ovary (CHO) cells under the control of the SV40
      early promoter using an expression construct, pX/Uf. The proportion of Uf
      secreted into the medium relative to the amount retained intracellularly
      increased as total Uf expression was increased. At transfection doses of 15
      micrograms pX/Uf per 10(6) cells, over 80% of the Uf produced in 48 h was
      secreted. A parallel situation was observed when human cathepsin D was
      overexpressed in CHO cells. Thus, high production of Uf, as occurs in the uterus
      in response to progesterone, may overwhelm the intracellular enzymatic and
      receptor systems that are normally employed to target acid hydrolases to
      lysosomes, resulting in secretion. Both Uf and cathepsin D secreted by CHO cells
      possess N-linked, phosphorylated high-mannose oligosaccharide chains. However,
      the phosphate groups on the oligosaccharide chains of Uf, unlike those on
      cathepsin D, cannot be readily removed by alkaline phosphatase treatment. These
      results suggest that the phosphate groups on Uf are masked at least partially by
      covering N-acetylglucosamine residues and that two mechanisms may contribute to
      hypersecretion of Uf in the uterus: 1) very high rates of synthesis and 2)
      partial masking of the mannose 6-phosphate recognition signal.

PMID- 8286615
TI  - Mammary somatosensory pathways are not required for suckling-mediated inhibition
      of luteinizing hormone secretion and delay of ovulation in cows.
AB  - Four experiments were conducted to evaluate endocrine, lactational, and
      reproductive features of an experimental animal model employing complete neural
      disconnection of the udder in beef cows and then to utilize the validated model
      to study the role of mammary somatosensory pathways in suckling-mediated
      anovulation. For experiment 1, crossbred beef cows (n = 16) were randomly
      assigned to suckled/sham-operated control, weaned (calf removed)/sham-operated
      control, and suckled/mammary-denervated groups between Days 14 and 18
      postcalving. Ten additional cows were randomly divided into weaned or suckled
      unoperated control groups (experiment 2). Complete mammary anesthesia was
      attained in all denervated cows (experiment 1), but sensory perception was not
      affected in sham-operated controls. Prolactin release patterns were markedly
      depressed by denervation; however, oxytocin release, milk production, and calf
      growth rates were not affected. Although acute sham surgery attenuated weaning
      induced increases in LH pulse and ovulation frequency (experiment 1), normal
      responses to weaning were observed in unoperated controls (experiment 2) as well
      as in sham-operated cows 1 yr later (experiment 3). Finally, denervated-suckled
      cows (n = 22) that had been denervated before conception (experiment 4) exhibited
      LH secretion patterns and mean postpartum intervals to luteal activity similar to
      those of intact-suckled cows (n = 16). In contrast, the intact-weaned group (n =
      16; calves weaned at birth) responded within 2 wk postcalving with an increased
      frequency of LH pulses, and intervals to onset of luteal activity were shortened
      compared to those in the other groups. Suckling-mediated anovulation is not
      dependent upon mammary somatosensory cues.

PMID- 8286616
TI  - Evidence for maternal behavior as a requisite link in suckling-mediated
      anovulation in cows.
AB  - Some component of the suckling process inhibits LH secretion and delays
      postpartum ovulation in beef cows. To investigate a possible role for maternal
      behavior in suckling-mediated anovulation, 27 crossbred beef cows were randomly
      allotted to 1 of 3 groups: 1) alien (dam suckled by alien calf; n = 11); 2) own
      (dam suckled by own calf; n = 8); and 3) weaned (calf removed for 6 days; n = 8).
      Beginning 14-17 days after parturition (experimental Day 0), cows were control
      suckled (10 min every 6 h) in stanchions for 6 days by either their own calf or
      by an alien calf or were weaned. Mean LH pulse frequencies in the alien and
      weaned groups were similar but were elevated (p < 0.02) on experimental Days 2
      and 4 compared to those in the own group. The incidence of luteal activity by
      experimental Day 10 was greater (p < 0.01) for the alien (72.2%) and weaned
      groups (75.0%) than for the own group (12.5%). Frequency of oxytocin release
      following suckling was greater (p < 0.01) in the own group than in the alien
      group (Day 2: 100% vs. 36.4%; Day 4: 100% vs. 54.6%), whereas suckling-induced
      release of prolactin was similar for both groups. Data provide evidence that the
      mother-offspring bond is an important link in suckling-mediated inhibition of LH
      secretion and ovulation.

PMID- 8286617
TI  - Expression of E-cadherin in immature rat and mouse testis and in rat Sertoli cell
      cultures.
AB  - Cadherins are Ca(2+)-dependent cell adhesion molecules that play essential roles
      in organogenesis. Northern blot analysis was used to determine the levels of
      epithelial (E)-, neural (N)-, and placental (P)-cadherin expression in developing
      rat testes from 1-, 2-, 3-, and 4-wk-old rats. Highest expression of all three
      cadherins occurred during the first two postnatal weeks, prior to the
      establishment of the blood-testis barrier. Transcripts of all three cadherins
      were also detected in RNA isolated from Sertoli cells cultured from 3-wk-old rat
      testes. Immunoblot analysis demonstrated levels of E- and P-cadherin protein in
      the testis and Sertoli cells that corresponded to the levels of their respective
      RNA transcripts. Immunohistochemical reactivity of E-cadherin in 8-day-old mouse
      testis was associated with germ cells situated basally in the seminiferous
      tubules. This report establishes the expression of E-cadherin in the testis and
      the simultaneous expression of E-, N-, and P-cadherin in both testis and Sertoli
      cell cultures.

PMID- 8286618
TI  - Effects of stimulation or inhibition of lipid peroxidation on freezing-thawing of
      mouse embryos.
AB  - This study was conducted to determine whether the tolerance of embryos to the
      stress of freezing and thawing can be modified by including in the incubation
      medium stimulators or inhibitors of membrane lipid peroxidation. Mouse zygotes
      were cultured in medium M16, supplemented or not with FeSO4, apotransferrin,
      and/or ascorbate. In each culture supplement, 8-cell embryos were randomly
      allocated to an untreated (nonfrozen) control group, or treatment by freezing
      using slow or ultra-rapid cooling. In the slow-frozen group, FeSO4 (49.3%, 66 of
      134), decreased embryo survival, whereas apotransferrin (82.7%, 110 of 133) and
      ascorbate (86.4%, 114 of 132), increased significantly the percentage of intact
      embryos recovered after thawing compared to those cultured in the basic medium
      M16 (66.9%, 99 of 148). Apotransferrin and ascorbate also increased significantly
      the percentage of blastocysts on Day 5 (79.7%, 106 of 133, and 89.4%, 118 of 132
      vs. 62.2%, 92 of 148, respectively). Ascorbate, in addition, increased
      significantly the percentage of implantations compared to those in the basic
      medium M16 (84.5%, 60 of 71 vs. 61.1%, 37 of 56). Changes in the ultra-rapidly
      frozen group were not so evident. However, a significant fetal wastage after
      implantation was observed when embryos were cultured without additives and then
      ultra-rapidly frozen (31.7%, 13 of 41 vs. 7.0%, 3 of 43, in the nonfrozen control
      group). Fetal weight was similar between culture conditions, but it was
      significantly lower in slow-frozen and ultra-rapidly frozen embryos than in the
      nonfrozen control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286619
TI  - Neuroendocrine mechanisms that control seasonal changes of luteinizing hormone
      secretion in sheep are sexually differentiated.
AB  - The apparent earlier onset of seasonal breeding activity of adult male versus
      adult female sheep suggests that the neuroendocrine mechanisms that control onset
      of the breeding season may be sexually differentiated in this species. However,
      it is difficult to compare gradual onset of testicular growth to abrupt changes
      in ovarian activity. To determine the relative timing of seasonal transitions in
      neuroendocrine reproductive activity, we compared temporal changes of LH
      concentrations in adult, gonadectomized, estradiol (E)-treated (experiment 1), or
      testosterone (T)-treated (experiment 2) Suffolk male and female sheep held
      outdoors for 18 mo. In addition, we compared the rates at which E-treated males
      and females become photorefractory to a winter solstice hold (WSH) photoperiod.
      In all three experiments, blood samples were collected weekly. In addition,
      serial blood samples were collected every 12 min for 4 h at approximately 2-mo
      intervals for experiment 1 and at monthly intervals for experiment 2. Neither
      plasma E nor T concentrations differed (p > 0.05) between sexes. In E-treated
      animals, mean LH changed (p < 0.001) over time in both sexes, and there was a sex
      x time interaction (p < 0.001). LH pulse amplitude changed (p < 0.001) over time
      in both sexes, but there was no detectable (p > 0.05) sex x time interaction. LH
      pulse frequency varied significantly over time in E-treated females (p < 0.001)
      but not in males (p < 0.05). The amplitude of the annual oscillation of mean LH
      was greater (p < 0.01) in E-treated females than in males.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8286620
TI  - Seasonal changes in gonadotropin-releasing hormone secretion in the ewe:
      alteration in response to the negative feedback action of estradiol.
AB  - Two experiments were performed to test the hypothesis that there is a seasonal
      change in the negative feedback effect of estradiol on episodic secretion of GnRH
      in the ewe. The first experiment identified a specific estradiol treatment
      (delivered by s.c. Silastic implant) that produced a 50% decrease in the
      frequency of pulsatile secretion of LH in ovariectomized ewes during the
      anestrous season. In the second experiment, this estradiol treatment was
      administered to ovariectomized ewes during the mid-breeding and anestrous
      seasons. Separate groups of ovariectomized ewes not treated with estradiol were
      included during each season to test for a seasonal difference in the effect of
      estradiol on episodic GnRH and LH secretion. Samples of hypophyseal portal blood
      (for GnRH) and jugular blood (for LH) were obtained at 5-min intervals
      approximately one month after placement of the estradiol implants. During the
      breeding season, no effect of estradiol was observed on either the frequency or
      size of GnRH and LH pulses. During anestrus, however, estradiol produced a
      profound suppression of the frequency of GnRH and LH pulses, and an increase in
      GnRH pulse size. No significant seasonal change was observed in the
      characteristics of GnRH and LH pulses in ovariectomized ewes in the absence of
      estradiol treatment. These findings lead to the conclusion that there is a marked
      seasonal change in the negative feedback effect of estradiol on episodic GnRH
      secretion in the ewe, with the steroid being maximally effective during anestrus.

PMID- 8286621
TI  - Instituting health care reform and preserving quality: role of the hospital
      epidemiologist.

PMID- 8286622
TI  - Cryptococcal meningitis and AIDS.
AB  - Dr. William G. Powderly provides a comprehensive review of the state of our
      knowledge regarding cryptococcal infection in persons with infection due to human
      immunodeficiency virus type 1. The introduction of fluconazole and itraconazole
      increased insight into prognostic factors affecting these patients. The need to
      suppress this fungal infection in individuals with impaired immunity has greatly
      altered the management of cryptococcal meningitis; therapy for this condition was
      established by the landmark study conducted by the Mycosis Study Group in 1979
      (Bennett JE, Dismukes WE, Duma RJ, et al. A comparison of amphotericin B alone
      and combined with flucytosine in treatment of cryptococcal meningitis. N Engl J
      Med 1979;301:126-31). In this AIDS commentary Dr. Powderly clearly outlines the
      progress made through clinical investigations and the problems that remain to be
      resolved.

PMID- 8286623
TI  - Nosocomial acinetobacter meningitis secondary to invasive procedures: report of
      25 cases and review.
AB  - The medical records of 25 patients with nosocomial meningitis due to
      Acinetobacter baumannii were retrospectively reviewed. Most cases occurred in the
      neurosurgical intensive care unit over a 5-year period, with an increased rate
      during summer. The majority of infections were associated with indwelling
      ventriculostomy tubes or CSF fistulae in patients receiving antimicrobial
      therapy. Repeated environmental cultures failed to reveal a source of the
      microorganism, and control measures had no apparent effect on the outbreak.
      However, no further cases appeared following a sharply reduced total intake of
      antibiotics in the neurosurgical department. Forty-one cases of acinetobacter
      meningitis, secondary to invasive procedures, were found in the English-language
      literature and were compared with the cases presented. To our knowledge, our
      series is the largest of acinetobacter meningitis reported hitherto. Although not
      one of the most common pathogens in hospitals, Acinetobacter constitutes an
      increasing threat for patients, especially those receiving antimicrobial therapy
      in intensive care units who are being maintained by various life-support systems.

PMID- 8286624
TI  - Fatal Israeli spotted fever in children.
AB  - We describe three Israeli children with fatal spotted fever. Clinical disease was
      characterized by irreversible shock, encephalopathy, renal failure, bleeding
      tendency, and death within 24 hours of admission. None of the patients had a
      history of tick bite, and no tache noire was noted. One child presented without
      rash, and the other two did not have antibodies to spotted-fever-group
      rickettsiae. The disease was confirmed by isolation of Rickettsia conorii from
      the patients' blood and tissues in cell cultures or from susceptible laboratory
      animals inoculated with human specimens. The present cases demonstrate the
      existence of a severe form of Israeli spotted fever in this population that
      resembles Rocky Mountain spotted fever. Because Israeli spotted fever may follow
      a quick, unpredictable, rapidly fatal clinical course, specific antimicrobial
      therapy should be promptly administered whenever the diagnosis is suspected.

PMID- 8286625
TI  - Cytomegalovirus polyradiculopathy caused by a ganciclovir-resistant strain.
AB  - Polyradiculopathy caused by cytomegalovirus (CMV) is a rare but serious
      neurological disorder that occurs late in the course of HIV-1 infection and is
      potentially treatable with antimicrobial agents active against CMV. We describe a
      patient with CMV infection caused by a strain that was resistant to ganciclovir.
      This case demonstrates one potential mechanism of therapeutic failure and
      illustrates the potential pathogenicity of strains that are resistant to
      antiviral drugs.

PMID- 8286626
TI  - Treatment of brain abscess with cefotaxime and metronidazole: prospective study
      on 15 consecutive patients.
AB  - The aim of the present investigation was to prospectively study the clinical and
      bacteriologic outcome of 15 consecutive patients with brain abscesses who were
      treated with surgical excision and cefotaxime (3 g every 8 hours) plus
      metronidazole (0.5 g every 8 hours) for at least 3 weeks. The patients were
      followed clinically and with computed tomographic (CT) examinations. All patients
      survived, and there were no recurrences within 1 year. CT scans showed an
      exponential decrease in the size of enhancement. Cultures of all six specimens
      obtained after < 24 hours of treatment with cefotaxime and metronidazole were
      positive compared with cultures of three of nine specimens obtained later (P =
      .017). Anaerobic bacteria were isolated from 2 of 3 patients given two doses of
      metronidazole or less compared with none of 12 given three doses or more (P =
      .029). Reversible side effects occurred in nine patients. It is concluded that
      cefotaxime plus metronidazole is an alternative treatment for brain abscess in
      addition to surgical excision because of their good abscess penetration, their
      ability to eradicate bacteria, and a good clinical outcome.

PMID- 8286627
TI  - Group II phospholipase A2 in sera of febrile patients with microbiologically or
      clinically documented infections.
AB  - Group II phospholipase A2 (PLA2-II) is an inflammatory enzyme, which has been
      shown to be an acute-phase protein and to correlate with the severity of sepsis.
      In a prospective study, the concentration of PLA2-II in the sera of 46 patients
      with sepsis and nonseptic bacterial and viral infections was measured by a
      fluoroimmunoassay. The serum concentration of PLA2-II in patients with infections
      (median, 164.5 micrograms/L; range, 5.07-1,740 micrograms/L) was elevated 46-fold
      above normal concentrations (median, 3.61 micrograms/L; range, 1.32-25.25
      micrograms/L). The concentration of PLA2-II was higher in patients with sepsis
      (median, 284.5 micrograms/L; range, 12.95-1,574 micrograms/L) and nonseptic
      bacterial infections (median, 210.6 micrograms/L; range, 5.07-1,740 micrograms/L)
      than in those with viral infections (median, 46.78 micrograms/L; range 11.46
      275.9 micrograms/L) (P = .0042). The concentration of PLA2-II correlated well
      with the concentration of C-reactive protein (CRP) (r = .613, P = .0001) but not
      with the concentration of pancreatic PLA2 (r = .089, P = .365). Measuring the
      serum concentration of PLA2-II is useful as an adjunct to the determination of
      CRP concentrations for differentiating bacterial from viral infection.

PMID- 8286628
TI  - Endocarditis due to Staphylococcus lugdunensis: report of 11 cases and review.
AB  - Staphylococcus lugdunensis is a recently described coagulase-negative
      staphylococcus that has been associated with human infections, including nine
      reported cases of infective endocarditis. The present study describes 11 other
      cases of infective endocarditis caused by this organism. The infection occurred
      in patients whose mean age was 61 years and was community-acquired in most cases.
      A preexisting cardiac abnormality was present in eight patients. Three of the 11
      infections involved prosthetic valves. Ten strains were susceptible to
      penicillin. The destructive course of the infection, the need for valve
      replacement, and the high mortality suggest that S. lugdunensis causes a virulent
      form of endocarditis.

PMID- 8286629
TI  - Infections caused by Pseudomonas pickettii in association with permanent
      indwelling intravenous devices: four cases and a review.
AB  - Permanent indwelling intravenous devices (PIIDs) have become increasingly
      prevalent in the past decade. These devices offer the advantage of long-term and
      convenient venous access, but their not-infrequent colonization by bacterial or
      fungi can lead to bloodstream infection with or without sepsis. We describe a
      series of four patients with PIIDs who became infected with Pseudomonas
      pickettii, and we review the properties of this unusual organism and the clinical
      presentation of the infections it causes.

PMID- 8286630
TI  - Invasive infection due to Apophysomyces elegans in immunocompetent hosts.
AB  - A previously well 59-year-old man developed necrotizing, invasive cellulitis and
      subsequent osteomyelitis at what was judged to be the site of a bite or sting.
      The pathogen isolated was Apophysomyces elegans. Eventually, in addition to
      treatment with intravenous amphotericin B, en bloc resection was required for
      cure. Only six previous cases of A. elegans infection have been reported in the
      literature. The lack of underlying disease in six of the total of seven cases
      contrasts with the usual findings for other zygomycoses. This article describes
      all seven reported cases as well as the characteristics of this unique fungal
      pathogen.

PMID- 8286631
TI  - A case of hyperdynamic shock caused by trimethoprim-sulfamethoxazole in which no
      tumor necrosis factor or features of anaphylaxis were detected.
AB  - An unusual acute hypotensive syndrome has been observed in association with
      administration of trimethoprim-sulfamethoxazole (TMP-SMZ) to patients with human
      immunodeficiency virus (HIV) infection. In the 11 cases that have been reported,
      the syndrome differs from classic anaphylaxis and resembles septic shock.
      Mediation by tumor necrosis factor (TNF) has been hypothesized, but the mechanism
      has not been characterized with cytokine assays, and no invasive hemodynamic
      measurements have been reported. We describe a case of recurrent hyperdynamic
      shock--without classic features of anaphylaxis, without detectable IgE antibodies
      against TMP or SMZ, and without detectable levels of TNF--involving an HIV
      infected patient rechallenged with TMP-SMZ.

PMID- 8286632
TI  - Failure of therapy with fluconazole for candidal endophthalmitis.
AB  - The incidence of candidemia and its complications, such as endophthalmitis, has
      measurably increased in recent years. However, the optimal method of treatment of
      hematogenous candidal infection remains a controversial issue. Traditional
      therapy with amphotericin B is associated with well-known adverse reactions. Many
      clinicians therefore prefer to use fluconazole, which is administered orally and
      is relatively less toxic. We recently observed a patient with candidal sepsis in
      whom blinding endophthalmitis developed despite aggressive and lengthy therapy
      with fluconazole. This grave clinical outcome and the data derived from
      experimental models of ocular candidal infection suggest that empirical usage of
      fluconazole may not be warranted in cases of disseminated candidiasis potentially
      complicated by endophthalmitis.

PMID- 8286633
TI  - Non-urinary tract infections caused by multiply antibiotic-resistant
      Corynebacterium urealyticum.
AB  - Five patients with non-urinary tract infections caused by Corynebacterium
      urealyticum were seen during an 8-year period at a university hospital in Madrid.
      Bacteremia (one case) and wound infections (four cases) were the most relevant
      features of these cases. Treatment with vancomycin, surgery, and supportive
      measures contributed to a favorable outcome for four of the five patients.

PMID- 8286634
TI  - Propionibacterium propionicum and infections of the lacrimal apparatus.
AB  - Analysis of the clinical details associated with 26 referred isolates of
      Propionibacterium propionicum revealed the marked propensity of this anaerobe to
      be involved with infections of the lacrimal apparatus; 18 (69%) of the 26
      referred isolates were from cases of canaliculitis in which this organism was
      regarded as the significant pathogen. Further analysis of data showed a
      significant correlation with the sex of the patient. Of the 18 cases of
      canaliculitis, the sex of the patient was reported in 16; 14 (88%) of these 16
      patients were females (P < .005). The age of 13 of the 18 patients with
      canaliculitis was known (mean, 61.6 years; range, < 1-80 years); it appears from
      these cases that P. propionicum lacrimal infections are more common in later
      life. None of the referred isolates were identified as Actinomyces species.
      Despite the fact that infection of the lacrimal apparatus is known as ocular
      actinomycosis, it appears that P. propionicum is more frequently associated with
      the condition than are true Actinomyces species.

PMID- 8286635
TI  - Epidemiology and etiology of pneumonia in children in Hong Kong.
AB  - The epidemiologic and etiologic features of cases of pneumonia among 1,740
      children admitted to a teaching hospital in Hong Kong over a 3-year period were
      studied. Of the patients, 23% were < 1 year old and 69% were < 5 years old. The
      incidence of pneumonia requiring admission to the hospital was 6.4 episodes per
      1,000 children per year for those < 5 years of age. The overall case fatality
      rate was 0.15% among patients who did not have severe underlying disease before
      contracting pneumonia. A bacterial etiology was confirmed by blood culture for
      only 2% of patients. However, culture of sputum or nasopharyngeal aspirates
      yielded predominant or pure growth of one bacterial agent in 17% of cases.
      Haemophilus influenzae was the bacterial agent most frequently isolated from
      nasopharyngeal aspirates or sputum, followed by Streptococcus pneumoniae and
      Staphylococcus aureus. Of the H. influenzae isolates, 38% were resistant to
      ampicillin. A viral etiology was proven in 9.1% of cases, and evidence of
      mycoplasmal infection was found in 3.8% of cases. Respiratory syncytial virus was
      the most frequently identified viral agent, followed by adenovirus and influenza
      A virus.

PMID- 8286636
TI  - Recent trends in the epidemiology of Shigella species in Israel.
AB  - Trends in the epidemiology of infections due to Shigella species over a period of
      6 years (1986-1991) in Israel were studied by analysis of the results of 51,300
      stool cultures, of which 2,987 yielded Shigella species. In a university
      hospital, the relative prevalence of Shigella sonnei in patients with shigellosis
      increased over the years from 60% in 1986 to 91% in 1991 (r = 0.93; P = .007);
      concomitantly, the prevalence of Shigella flexneri decreased from 29% to only 8%
      (r = -0.80; P < .05). In the community, the increase in prevalence of S. sonnei
      was more moderate and occurred only from 1989 to 1991. Since 1990, S. sonnei has
      been isolated from more hospitalized patients than has S. flexneri, in contrast
      to their rates of isolation in the past. The increase in prevalence of S. sonnei
      was most prominent among children, in whom it caused 94% of shigella infections
      in 1991. Shigella boydii and Shigella dysenteriae remained relatively rare,
      causing approximately 5% and approximately 1%, respectively, of the cases of
      shigella infection. Concomitantly, the antimicrobial resistance of S. sonnei has
      become significantly greater, and it is currently 2.7 and 1.6 times higher than
      that of S. flexneri to trimethoprim-sulfamethoxazole and ampicillin,
      respectively. We conclude that the relative frequency of S. sonnei is increasing,
      especially in hospitalized patients, and hypothesize that this may be related to
      its increasing antimicrobial resistance. These trends have clinical implications.

PMID- 8286637
TI  - Efficacy of ivermectin in the treatment of strongyloidiasis complicating AIDS.
AB  - Nine adult male homosexuals who were infected with the human immunodeficiency
      virus (five with AIDS-defining conditions) and harbored Strongyloides stercoralis
      received ivermectin on a compassionate basis for persistent intestinal infection.
      Hyperinfection was present in all cases. Ivermectin was given either as a single
      oral dose (200 micrograms/kg) or on a multidose schedule (200 micrograms/kg.d) on
      days 1, 2, 15, and 16. All seven patients who received multiple doses showed
      sustained clinical and parasitological cure, whereas one of two patients who
      received single-dose therapy relapsed promptly and fatally. Remissions have been
      maintained for at least 7 months and up to 3 years of follow-up. Ivermectin
      appears promising in the treatment of strongyloidiasis in patients with AIDS.
      Because of the risk of hyperinfection and/or disseminated disease, multidose
      courses are warranted. We are not aware of other reports describing the efficacy
      of antiparasitic drugs for strongyloidiasis in patients with AIDS.

PMID- 8286638
TI  - Persistent infection with Ehrlichia chaffeensis.
AB  - Although persistent infection of animals by members of the genus Ehrlichia is
      well known and may be associated with subsequent severe or fatal illness,
      persistent infection of humans with Ehrlichia chaffeensis has not been reported.
      Herein we report a typical case of serologically documented acute ehrlichiosis;
      despite therapy with tetracycline and chloramphenicol, the patient's condition
      progressively worsened and he suffered multiple secondary infections and
      gastrointestinal hemorrhage. He died 68 days after his initial hospitalization.
      Retrospective immunohistologic examination of both acute-phase bone marrow
      specimens (obtained day 12 of illness) and postmortem liver tissue specimens
      (obtained day 68 after onset of disease) revealed E. chaffeensis morulae in
      mononuclear cells, presumably macrophages and monocytes. Findings of this case
      provide the first definitive evidence that E. chaffeensis is capable of
      establishing persistent human infection and suggest a role for this obligate
      intracellular bacterium in the induction of immune compromise associated with a
      fatal outcome.

PMID- 8286639
TI  - Invasive aspergillosis in liver transplant recipients: association with
      candidemia and consumption coagulopathy and failure of prophylaxis with low-dose
      amphotericin B.
AB  - Invasive aspergillosis developed in three (5%) of 55 adult liver transplant
      recipients at our institution. All three of our patients had concomitant
      candidemia and consumption coagulopathy, and invasive aspergillosis developed
      while they were receiving therapy with intravenous amphotericin B (0.5
      mg/[kg.d]). The simultaneous occurrence of candidemia and invasive aspergillosis
      in liver transplant recipients may reflect a common defect in the host-defense
      mechanism against Candida and Aspergillus organisms (i.e., impaired phagocytic
      and mononuclear macrophage function) and liver disease per se. These three cases
      suggest that such low-dose intravenous amphotericin B will likely be ineffective
      if used as antifungal prophylaxis for invasive aspergillosis.

PMID- 8286640
TI  - Human intestinal capillariasis in an area of nonendemicity: case report and
      review.
AB  - We report a rare case of human intestinal capillariasis in a young Colombian man
      who presented with abdominal pain and mild, self-limited diarrhea. Capillaria
      eggs were visualized in the feces, and treatment with mebendazole (200 mg/d for 3
      weeks) resulted in clinical and parasitological cure. To our knowledge, this is
      the first case in a South American person and the second case reported in Europe.
      This case highlights the acquisition of endemic intestinal parasitosis far away
      from classically considered areas of endemicity. We review the English-language
      literature on human intestinal capillariasis and compare findings from other
      cases with those from the current case.

PMID- 8286641
TI  - A brief history of the pneumococcus in biomedical research: a panoply of
      scientific discovery.
AB  - Because of its prominence as a cause of disease in humans, Streptococcus
      pneumoniae has been the subject of intensive investigation at both the clinical
      level and the basic scientific level during the past century. In a number of
      instances, these studies have resulted in important progress toward the
      comprehension of basic biological principles. The areas advanced by studies of
      the pneumococcus include an understanding of the concept of pathogenesis of
      infectious disease; the development of Gram's stain for identification of
      bacteria in specimens from patients; the elucidation of the role of the bacterial
      capsule in resistance to phagocytosis by cells of the host's immune system; the
      demonstration that molecules other than proteins are capable of eliciting the
      host's humoral immune responses and later, by extension, that isolated bacterial
      exopolysaccharides can be used safely and effectively as vaccines in humans; the
      documentation of the efficacy of penicillin; the collection of conclusive
      evidence that DNA encodes genetic information; and the investigation of putative
      proteinaceous virulence factors.

PMID- 8286642
TI  - Pneumonia due to Chlamydia pneumoniae strain TWAR.

PMID- 8286643
TI  - Thrombocytopenia due to use of teicoplanin.

PMID- 8286644
TI  - Varicella lesions and Woronoff's ring.

PMID- 8286645
TI  - Multiple sclerosis and hepatitis B vaccination.

PMID- 8286646
TI  - Cellulitis associated with bacteremia due to Flavobacterium meningosepticum.

PMID- 8286647
TI  - Three cases of fatal infection due to Fusarium solani in patients with cancer.

PMID- 8286648
TI  - A case of meningitis due to "Streptococcus zooepidemicus".

PMID- 8286649
TI  - Cervicofacial nocardiosis caused by Nocardia brasiliensis in an adult.

PMID- 8286650
TI  - Nosocomial infection of a pancreatic pseudocyst due to Corynebacterium xerosis.

PMID- 8286651
TI  - Malaria in splenectomized patients.

PMID- 8286652
TI  - Management of respiratory diphtheria.

PMID- 8286653
TI  - Pyogenic abscess of the gluteal muscle due to Streptococcus pneumoniae.

PMID- 8286654
TI  - Azathioprine hypersensitivity mimicking sepsis in a patient with Crohn's disease.

PMID- 8286655
TI  - Herpes simplex virus type 2 DNA in cerebrospinal fluid of a woman with recurrent
      meningitis.

PMID- 8286656
TI  - Training in invasive procedures for infectious diseases specialists.

PMID- 8286657
TI  - Don't forget Leishmania!

PMID- 8286659
TI  - Variation in physicians' recording of human immunodeficiency virus--associated
      risk behavior among socioeconomically diverse populations.

PMID- 8286658
TI  - Prosthetic valve endocarditis due to Rothia dentocariosa.

PMID- 8286660
TI  - Localized cutaneous Rhizopus presenting as an anesthetic rash in a patient
      infected with human immunodeficiency virus.

PMID- 8286661
TI  - Postoperative pancreatic abscess due to Haemophilus influenzae.

PMID- 8286662
TI  - Breast abscess due to Salmonella serogroup B, serotype Reading, in a young
      nonpuerperal woman.

PMID- 8286663
TI  - Goiter as a manifestation of disseminated aspergillosis in a patient with AIDS.

PMID- 8286664
TI  - Septic shock due to Yersinia enterocolitica after autologous transfusion.

PMID- 8286665
TI  - Cutaneous infection due to Aspergillus species after transthoracic lung biopsy.

PMID- 8286666
TI  - Trivalent metal ions in the prevention of calcification in glutaraldehyde treated
      biological tissues. Is there a chemical correlation?
AB  - The influence of chemical factors on trivalent metal ions in the prevention of
      calcification of glutaraldehyde treated biological tissue has been explored. The
      results indicate that the chemical link lies in the hard character of the
      trivalent metal ions. Metal ions with the hardest character appear to have the
      best chance of reacting with oxygen atoms of the phosphate groups at nucleation
      sites of hydroxyapatite. This disrupts the nucleation and thus prevents
      calcification in glutaraldehyde treated biological tissue.

PMID- 8286667
TI  - Interfacial photopolymerization of poly(ethylene glycol)-based hydrogels upon
      alginate-poly(l-lysine) microcapsules for enhanced biocompatibility.
AB  - The biocompatibility of microcapsules made by the co-acervation of alginate and
      poly(l-lysine) (PLL) was enhanced by coating the surface of these microcapsules
      with a poly(ethylene glycol) (PEG)-based hydrogel. The hydrogel was formed by an
      interfacial photopolymerization technique using visible light from an argon ion
      laser. The light absorbing chromophore, eosin Y, was immobilized on the
      microcapsule surface. This restricted the formation of the PEG hydrogel to the
      surface of the microcapsule. The presence of the PEG gel on the surface was
      confirmed by fluorescent dextran entrapment, by direct visualization after
      dissolution of the underlying membrane and by electron spectroscopy for chemical
      analysis. The biological response of such microcapsules was evaluated by
      intraperitoneal implantation in mice. The PEG-coated microcapsules were found to
      be less inflammatory and were seen not to elicit a fibrotic response, as was the
      case with alginate-PLL microcapsules.

PMID- 8286668
TI  - Press-coated tablets for time-programmed release of drugs.
AB  - A new dry-coated device for the release of drug after a programmable period of
      time is proposed. It is intended to be used mainly in the therapy of those
      diseases which depend on circadian rhythms. Some core formulations, characterized
      by different release rates and mechanisms (containing diltiazem hydrochloride or
      sodium diclofenac as model drugs), were coated by compression with different
      polymeric barrier layers (press-coated systems). The shell formulations tested
      contained either gellable or erodible polymers. The dissolution profiles of
      uncoated cores and press-coated devices were compared. The gellable and/or
      erodible characteristics (properties) of the barrier formulations were also
      examined by means of a penetrometer. The coatings prevent drug release from the
      core until the polymeric shell is completely eroded or swollen. This delay in
      release start is not influenced by the core composition and depends only on the
      shell formulation. Except for the time-lag, the release kinetics of the drug
      contained in the core are not significantly influenced by the presence of the
      erodible barrier, but can be widely modulated using a swellable polymeric shell.

PMID- 8286669
TI  - Biocompatible and biodegradable polyurethane polymers.
AB  - This study deals with the opportunities for the synthesis of biocompatible and
      biodegradable polyurethane adhesives which are suitable for application as wound
      dressings. Three different synthetic possibilities have been investigated. The
      relationships between some reaction factors and the final properties of the
      obtained products are pointed out. The toxicity of the investigated urethane
      acrylates, polyurethanes and combined polyurethane adhesives is also studied.

PMID- 8286670
TI  - Re-freeze dried bilayer artificial skin.
AB  - A bilayer artificial skin composed of a silicone sheet and a collagen sponge
      sheet was developed by us in 1986, modifying Yannas and Burke's technique. It was
      used in experimental animals and clinically, both with success; but the
      artificial skin was inconvenient for clinical use in terms of disinfection and
      preservation. In an attempt to reduce the drawbacks, we developed a re-freeze
      dried artificial skin. Experiments were conducted to examine whether the re
      freeze dried material is equivalent to the prototype one. A significant
      difference between the two was found in tensile tests but not in experimental and
      clinical effects.

PMID- 8286671
TI  - Bending stiffness of conical and standard external fixator pins.
AB  - The bending stiffnesses of a conical and a standard external fixator pin have
      been compared. The pins were inserted into pilot holes in a piece of teak
      hardwood and loads of different magnitudes were applied at a fixed moment arm.
      Force-deflection curves were obtained for each pin, and stiffness (newtons per
      metre) and percentage stiffness reduction were calculated for each pilot hole
      size. The results show that deflection increased (i.e. stiffness decreased) with
      increasing force or diameter of pilot hole. This loss of stiffness was linear for
      the standard pin but was bimodal for the conical pin.

PMID- 8286672
TI  - Toxicity of silica-containing calcium phosphate glasses.

PMID- 8286673
TI  - Induction and morphology of hydroxyapatite, precipitated from metastable
      simulated body fluids on sol-gel prepared silica.
AB  - Hydroxyapatite crystallization is induced at 37 degrees C by sol-gel prepared
      silica from metastable calcium phosphate solutions. The morphology of the apatite
      forming on the silica surface depends on the nature of the solutions. For
      example, apatite grew in a flake-like form at pH 7.4. The morphology changed to
      plate-like when the pH was adjusted to pH 7.2. At this lower pH, the apatite
      plate even exhibited a hexagonal feature, reflecting the unique hexagonal
      structure of hydroxyapatite. An increase in either Mg or P ion concentration of
      the fluid can cause apatite to grow in a rod-like shape while addition of F ions
      to the fluid leads to a perfect needle pattern. The flake geometry of apatite was
      not altered by increasing Ca concentration from 2.5 to 3.8 mM in the solution.
      From this we conclude that sol-gel prepared silica is an efficient apatite
      inducer and the morphology of the hydroxyapatite deposit is determined by factors
      of the fluid such as pH, Ca/P molar ratio, Mg and F concentrations.

PMID- 8286674
TI  - Relationship between the colour change of hydroxyapatite and the trace element
      manganese.
AB  - Hydroxyapatite containing the trace element manganese turns blue after sintering
      at high temperature in an oxidizing atmosphere. This phenomenon is related to the
      oxidation of manganese ions in the special crystal structure of hydroxyapatite.
      Combination of the crystal structure with electron spin resonance spectra gives
      an explanation for this oxidation of Mn2+ ions at Ca(l) sites into Mn5+ ions and
      the formation of MnO4(3-) ions at PO4(3-) sites, corresponding to the colour
      change of hydroxyapatite.

PMID- 8286675
TI  - Bone ingrowth into hydroxyapatite coating: a light microscopy and laser scanning
      microscopy study.
AB  - The authors present a description of the presence of organic material inside the
      hydroxyapatite (HA) coating of Calcitek implants inserted in rabbit tibia. Light
      microscopy showed that in all specimens a granular basophilic material which was
      not mineralized was present inside the thickness of the coatings. In two
      specimens out of 40, a bone-like substance was observed in some areas of the
      coating, at a distance from the interface. Laser scanning microscopy showed in
      all specimens an autofluorescence of osteocytes, osteoblasts, of the interface,
      and inside the coating. The presence of bone could either show an ability of the
      coating to serve as a scaffold for the newly forming osseous tissue or be a sign
      of an initial degradation of the HA.

PMID- 8286676
TI  - Molecular interface characterization in human bone matrix. I. Biochemical and IR
      spectroscopic studies.
AB  - The aim of this work is the characterization of interfaces in calcified tissues.
      In order to separate the non-collagenous bone proteins, according to their
      interaction with collagen or hydroxyapatite crystals, 10 sequential bone
      demineralizations using EDTA alone were carried out, followed by four sequential
      extractions using both EDTA and GuHCl. The extracts were characterized by SDS
      PAGE, IR spectrum analysis, and kinetics of demineralization and proteins
      released. A great proportion of non-collagenous proteins are bound to the
      collagen matrix, many of which have a high affinity to it. This work demonstrates
      that collagen is not directly linked to the mineralized phase.

PMID- 8286677
TI  - Predictive modelling of hydroxyapatite-polyethylene composite.
AB  - A predictive model for hydroxyapatite-reinforced polyethylene composite has been
      developed using the finite element analysis method. The simulation is based on
      the analysis of a representative cell. Results for the complete material can be
      derived using a spatial statistical material model. Predicted values of Young's
      modulus are found to be in reasonable agreement with experimentally measured
      values over a wide range of hydroxyapatite volume fraction. The predictive model
      can be used to investigate the micromechanical behaviour of the material. This
      investigation leads to significant elucidation of the failure processes for this
      material.

PMID- 8286678
TI  - Effect of ethylene oxide sterilization on human demineralized bone.
AB  - Demineralized human bone used as an autologous bone graft substitute is ethylene
      oxide sterilized, which is reported to reduce the bone's osteoinductive
      potential. To determine the minimum sterilization time required and the effect of
      ethylene oxide on bone's osteoinductive capacity and chemical structure, samples
      were exposed to ethylene oxide for different times (5-240 min). Results showed
      that 1 h exposure sterilized the bone (assessed by Attests). This exposure time
      reduced the bone's osteoinductive potential and caused surface ultrastructural
      changes. These findings raise questions concerning the suitability of ethylene
      oxide for sterilizing demineralized human bone.

PMID- 8286679
TI  - Elastic and fracture properties of dental direct filling materials.
AB  - Five dental direct filling materials were tested in tension and compression in
      order to define their stress-strain behaviour for both types of applied stress.
      In addition, fracture toughness was determined from three-point bending tests.
      Linear and non-linear stress-strain behaviour was observed, and the response was
      specific for each material and also to the type of applied stress. Fracture
      resistance was also found to be material specific, which was related to
      differences in composition.

PMID- 8286680
TI  - Office gynecology.

PMID- 8286681
TI  - Victims of rape: the physician's role in treatment.
AB  - Physicians are seeing an increasing number of women who have experienced rape.
      Proper collection of physical evidence and thorough documentation during the
      initial examination are essential for potential use in the legal system.
      Psychological support and follow-up care for sexually transmitted diseases
      (STDs), the victim's emotional recovery, and return to normal functioning are
      also the sine qua non components for the woman's transition from victim to
      survivor of rape. In the past 2 years several articles have been published on the
      initial physical examination after the rape. In addition, there are increasing
      numbers of publications on the emotional and follow-up components of care. This
      article is an attempt to demonstrate the need for both components of care.

PMID- 8286682
TI  - Vulvitis and vaginitis.
AB  - Although the vulva and vagina are embryologically and histologically different,
      proximity results in inflammatory conditions which commonly affect both regions.
      Patients often confuse 'vulvitis' and 'vaginitis' in characterizing symptoms. It
      is the job of the clinician to recognize inflammatory conditions specific to
      vulva and vagina, as well as to understand that inflammatory conditions can often
      involve both areas. This review of recent literature does not pretend to be
      comprehensive. Rather, it highlights specific conditions and research questions
      of recent interest.

PMID- 8286683
TI  - Office sonography and office hysteroscopy.
AB  - Researchers involved in assessing technology and healthcare, including
      gynecologic care, have identified differences among the terms efficacy,
      effectiveness and efficiency. In order to assess the efficiency of procedures
      such as office sonography and hysteroscopy, it is first necessary to compare them
      with the alternatives in terms of patient-focused outcomes. Office sonography has
      been used to diagnose early pregnancy disorders such as ectopic gestations and
      evaluate other adnexal pathology, with mixed results. The use of office
      hysteroscopy to assess abnormal bleeding may replace procedures that are
      associated with greater risk and expense. More information regarding outcomes is
      needed for both procedures before they can be recommended as efficient
      alternatives for the diagnosis or treatment of gynecologic conditions.

PMID- 8286684
TI  - Chronic pelvic pain.
AB  - Chronic pelvic pain is a complex problem with a long history of attempts to
      elucidate the cause and to design effective therapies. This review is structured
      around recent articles in the field which contribute to our understanding,
      support certain therapeutic approaches, or describe a specific case. The pain
      aspects of endometriosis are included for their contribution to our understanding
      of pain and the difficulty encountered in managing these patients.

PMID- 8286685
TI  - Benign breast disease.
AB  - Most women initially consult their gynecologist when they have concerns about
      breast disorders. Although breast cancer is usually the patient's biggest fear,
      it is benign breast disease, a common disorder, which often complicates a
      thorough evaluation and which interferes with the early diagnosis of breast
      cancer. This article summarizes the current state of knowledge on the cause,
      diagnosis, and prognosis of selected benign breast disorders. Recent progress
      includes a promising line of research on the content of cyst fluids, better
      definition of breast cancer risk, and increasing acceptance of ultrasound
      techniques to differentiate cystic from solid masses.

PMID- 8286686
TI  - The genital examination of the infant through adolescence.
AB  - The genital examination of the young female is a relatively new procedure for
      many clinicians. It was not felt important until physicians became involved with
      the examination of survivors of childhood sexual abuse; from these examinations
      it is apparent that young females also have a broad array of genital conditions
      which need clinical evaluation and intervention. This review of the recent
      literature on the techniques employed by a variety of clinicians demonstrates the
      limitations placed on our knowledge of pediatric and adolescent gynecologic
      conditions by technical and psychosocial parameters.

PMID- 8286687
TI  - Congenital anomalies of the female reproductive tract.
AB  - External and internal anomalies can result from enzyme or chromosome defects, and
      prenatal drug exposure. Major new developments in this field include better
      understanding of the genetics of enzymatic defects, laparoscopic and
      hysteroscopic modifications of older procedures, the advent of magnetic resonance
      imaging for diagnosis, and better understanding of the psychosocial impact and
      timing of therapy.

PMID- 8286688
TI  - Development of children and adolescents: physiological, pathophysiological, and
      therapeutic aspects.
AB  - Luteinizing hormone (LH) secretion is pulsatile with nocturnal augmentation even
      in prepubertal children, though at very low concentrations. With puberty wake
      time, LH concentration increases 100-fold. Rising estradiol levels transiently
      increase growth hormone (GH) concentrations, which in turn leads to increases in
      insulin-like growth factor (IGF)-I, insulin resistance, and physiological hyper
      insulinemia. In addition to estrogens, GH-IGF are important in accretion of bone
      mineral density (BMD) in puberty, and hypofunction may cause permanent low bone
      density. Growth hormone treatment of girls with Turner syndrome increases final
      height.

PMID- 8286689
TI  - Sexuality: sexual activity and contraception during adolescence.
AB  - Adolescent sexual activity is increasing. Premature sexual intercourse results in
      high figures of adolescent pregnancy and abortion, as well as in increased risk
      of sexually transmitted diseases (STDs). Lack of information on the prevention of
      STDs and poor hygiene in both boys and girls are also main reasons for increased
      morbidity because of STDs during adolescence. Contraceptive behaviour during
      adolescence varies between countries and communities. It seems, however, that the
      condom and oral contraceptives (OC) are popular contraceptive methods.
      Ineffective methods such as periodic abstinence, coitus interruptus, and
      withdrawal before ejaculation are in use. On the other hand, compliance of
      adolescents on contraception is poor. The above are additional causes for
      increasing rates of adolescent pregnancies. Countries providing sexual education
      programs in schools present lower rates of pregnancy and abortion. Adolescent
      pregnancy is safe if a careful follow up is accepted by the teenager. A
      significant number of homeless youth are homosexuals or lesbian adolescents. Most
      of them are at high risk for HIV infection, AIDS, and STDs. It is concluded that
      sexual education programs are absolutely necessary to offer adolescents the
      knowledge on the complications of premature sexual activity, as well as
      prevention of the undesired pregnancy and STDs.

PMID- 8286690
TI  - Child sexual abuse.
AB  - Child sexual abuse is being recognized as a common and serious problem which
      affects children regardless of their age, sex, socio-economic class, or
      geographic location. Children of all ages, from infancy to young adulthood, have
      been victims of abuse. It is well accepted that the number of reported incidents
      of child sexual abuse represents only a portion of the actual number of victims.
      The National Center on Child Abuse and Neglect estimates the number of child
      victims to be more than 200,000 per year. Many of these children are brought to
      emergency facilities or to their private physician's office for evaluation. Many
      physicians have difficulties in correctly identifying and managing child-victims
      of sexual abuse. The purpose of this chapter is to review the most recent
      advances in the medical evaluation of children who are the victims of sexual
      abuse.

PMID- 8286691
TI  - Family planning.

PMID- 8286692
TI  - The impact of family planning on women's health.
AB  - Approximately half a million women in developing countries die each year as a
      result of complications during pregnancy. Sadly, illegal abortion is one of the
      five major causes of these deaths. International data suggest that maternal
      mortality is decreasing in regions where the use of family planning is increasing
      because of the consequent avoidance of unwanted pregnancies, although accurate
      data on maternal mortality are difficult to obtain in most developing countries.
      Use of family planning to delay first births and to increase interpregnancy
      intervals has the potential to decrease infant mortality by at least 20%. Data
      from developing countries show that some of this potential has already been
      realized during the past 20 years, but additional improvement is possible. In
      countries where maternal mortality is low, women may avoid using contraceptives
      because of the perceived dangers of the most effective methods. Recent analyses
      show that cardiovascular risks associated with oral contraceptives are low, and
      that the net effect of oral contraceptives on cancer of the ovary and endometrium
      is one of protection. While there remain unanswered questions regarding cervical
      and breast cancer, the net effect is small at worst.

PMID- 8286693
TI  - Family planning in the teen population.
AB  - As an increasing percentage of adolescents reach their sexual debut at younger
      ages, effective contraceptive methods, which will decrease the risks of
      unintended pregnancies and sexually transmitted diseases (STDs), become even more
      critical. Contraceptive methods which are less 'compliance-dependent', such as
      the implantable subdermal levonorgestrel and the injectable depot formulation of
      medroxyprogesterone acetate, are popular in adolescents but careful counseling
      before method selection and on-going counseling when side-effects are experienced
      are necessary and essential. The use of condoms to decrease the risks of STDs
      will continue to be important for adolescents, and it remains to be seen what
      impact the long-term methods will have on effective condom use. Adolescents'
      access to abortions when contraceptive methods fail, or when no method is used,
      is being challenged with state laws which mandate parental notification or
      permission. A greater knowledge about the option of emergency contraception could
      potentially lead to increased use of this method, particularly when the option of
      medications such as RU486 becomes available. The potential for a reduction in
      unintended pregnancies in adolescents, and a reduced need for abortions is a
      welcome prospect.

PMID- 8286694
TI  - Recent experience with and future directions of contraceptive implants and
      injectable contraceptives.
AB  - Subdermal implantable contraception has been the most important addition to
      contraceptive technology in the past 2 decades. The Norplant system is only the
      first of a new family of long acting methods of high effectiveness, high
      acceptability, and prompt reversibility. The main advantage of the second
      generation implant systems, to be available soon, is the reduction in the number
      of implants, which greatly facilitates insertion and removal. However, great
      improvement in bleeding control is not to be expected. Large and carefully
      designed epidemiological studies have contributed to clear the main objections to
      the US Food and Drug Administration (FDA) approval of depot medroxyprogesterone
      acetate (DMPA) as an injectable contraceptive. New progestin-only, long acting
      injectables are being tested, but significant improvements over existing methods
      are difficult to foresee, although every alternative is welcome. Monthly combined
      injectables have been in great demand, at least in China and Latin America,
      because of better bleeding control. Improved combined monthly injectables, less
      estrogenic and more progestin dominated, have been developed and are being
      introduced in several countries and should soon replace the old monthly
      injectables. Contraceptive implants and injectables have shown to be an important
      addition to the contraceptive options available to women throughout both the
      developing and developed world.

PMID- 8286695
TI  - Contraception in lactating women.
AB  - Lactating women need contraception after first menses, supplementation or 6
      months postpartum, or before, according to personal or programmatic reasons. Non
      hormonal methods have no influence on lactation and are the first choice.
      Intrauterine devices (IUDs) inserted during amenorrhea are safe and show good
      continuation rates. Progestin-only methods do not affect breast-feeding and
      should be used after 6 weeks to prevent transference of orally active steroids to
      the newborn. Progesterone rings and Nestorone implants are effective new methods,
      that use orally inactive steroids.

PMID- 8286696
TI  - Contraception choice and sexually transmitted disease.
AB  - Sexually active couples need to be concerned with the risk of sexually
      transmitted diseases (STDs) and how their choice of contraception influences that
      risk. Condoms provide the best documented protection against such pathogens as:
      gonorrhea, herpes simplex virus (HSV), hepatitis B, HIV, and chlamydia. Female
      dependent barrier methods also provide protection against most STDs and also
      possibly HIV. Most hormonal non-barrier contraceptives, although providing
      excellent protection against unwanted pregnancies, provide little protection
      against STDs. Oral contraceptive pills (OCP) may increase the risk of infection
      with human papillomavirus (HPV) and cervical infections of chlamydia. Individuals
      at high risk for both an unwanted pregnancy and an STD should be counseled to use
      both a hormonal and barrier contraceptive. Recently, nonoxynol-9 (N-9) and OCP
      use have been associated with an increase in HIV infection in African women at
      high risk for HIV. This association has not been found in other studies and
      currently does not outweigh the proven benefits of these contraceptive methods.

PMID- 8286697
TI  - The intrauterine device in the present and future.
AB  - Good counseling and better selection of candidates would result in the
      intrauterine device's (IUD) safer use. Age and parity of the IUD acceptor do not
      seem to be associated with an increased risk of pelvic inflammatory disease
      (PID). The newer generation of copper- and hormone-releasing IUDs are associated
      with improved safety and efficacy.

PMID- 8286699
TI  - Office gynecology.

PMID- 8286698
TI  - Current controversies and future direction of oral contraception.
AB  - Despite their general use for more than 30 years there is ongoing controversy
      within the medical community and the lay press about the safety of oral
      contraceptive pills (OCPs). Cervical cancer and breast cancer continue to
      dominate as controversial issues. Presently, many experts agree that OCPs may
      accelerate the growth of early breast cancer in certain subgroups of younger
      women, e.g. with initiation at an early age, before the first pregnancy, when
      used long term. They do not agree on the profile of the woman at risk, whether
      this risk continues with older women, and whether the risk is of such
      significance for certain women that they should not take OCPs. Resolution of
      issues about risks of dysplasia and invasive cervical cancer will be difficult
      because of the many variables contributing to causation. It is more of a problem
      in areas of the world where routine Papanicolaou smears are not available.
      Controversy continues as to which of the new progestins, norgestimate,
      desogestrel, or gestodene offers the greatest advantages to OCP users. This is
      particularly true in the case of gestodene. Only further research will elucidate
      such questions. There is significant disagreement as to the root causes of high
      user failure rates with OCPs and how to remedy these. Some experts believe that
      making OCPs available off prescription and without direct medical supervision is
      the way to proceed, although other strongly disagree, citing the need to require
      regular Papanicolaou smears and check-ups to rule out sexually transmitted
      diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286701
TI  - Family planning.

PMID- 8286700
TI  - Adolescent and pediatric gynecology.

PMID- 8286702
TI  - Coding of odor intensity.
AB  - A model for coding of odor intensity in the first two neuronal layers of
      olfactory systems is proposed. First, the occupation and activation by odorant
      molecules of receptor proteins of different types borne by the first order
      neurons are described as birth and death processes. The occupation (birth) rate
      depends on the concentration of the odorant, whereas the probability of
      activation of an occupied receptor depends on the type of the odorant. Second,
      the spike generation mechanism proposed for the first order neuron depends on the
      level of the generator potential evoked by the activated receptors and on a time
      decaying threshold which is reset to infinity after each spike. The various
      resulting stochastic regimes of firing activity at different concentrations are
      described. Third, each second order neuron is influenced by excitation coming
      from numerous first order neurons, lateral inhibition from other second order
      neurons, and self-inhibition. All these incoming signals are integrated at the
      second order neuron. The firing activity of the first and second order neurons is
      modeled by a first passage time scheme. For both types of neuron the shapes of
      the curves predicted by the model for the mean firing frequency as a function of
      stimulus concentration are shown to be in accordance with available experimental
      results.

PMID- 8286703
TI  - Non-discrete biomolecular computing: an approach to computational complexity.
AB  - General principles of information processing at the molecular level inherent in
      simple biological and biomolecular entities can be used to elaborate essentially
      new non-discrete information-processing devices. These principles are: giant
      parallelism of information processing; processing mechanisms based on complicated
      non-linear dynamics; high efficiency of information transformations; considerable
      behavioral complexity of computational (pseudoelementary) primitives; and the
      possibility of variation and evolution of the molecular components of information
      processing devices, including the possibility of evolutionary learning. Problems
      of high computational complexity are currently of great practical importance. Non
      discrete biomolecular information-processing devices seem to be able to solve
      effectively some classes of problems of high computational complexity.

PMID- 8286704
TI  - Persistence of a four species food chain with full omnivory.
AB  - We consider here a food chain composed of four species with full omnivory with
      Lotka-Volterra dynamics. Conditions for uniform persistence and weak persistence
      of the food chain are derived. It is also shown that the system exhibits a
      heteroclinic cycle.

PMID- 8286705
TI  - The effect of diffusion on two predators exploiting a resource.
AB  - This paper deals with the stabilizing effect of diffusion on a system of a living
      resource supporting two noncompeting predators. It is shown that while the three
      species mathematical model without diffusion is unstable, the model with
      diffusion is asymptotically stable provided the diffusion coefficient of the
      resource exceeds a certain threshold value.

PMID- 8286706
TI  - World and regional populations.
AB  - Non-linear regression indicates that the logistic model provides excellent fits
      to world and continental human population data of the period 1950-1985. If the
      present logistic regime persists, the world population is likely to double in 47
      years. Moreover, the eventual world population would be close to its final value
      of 23.8 billion by the year 2200, with about 11 billion in Asia and 10.5 billion
      in Africa. An approximately 95% confidence interval for the eventual world
      population is found to be between 11.9 and 35.7 billion. The logistic estimates
      of future populations are much higher than those considered most likely by the
      United Nations.

PMID- 8286707
TI  - Quantum mechanical properties of biosystems: a framework for complexity,
      structural stability, and transformations.
AB  - Internal quantum non-demolition measurements are inherent for biological
      organization and determine the essential features of living systems. Low energy
      dissipation in these measurements provided by slow conformational relaxation of
      biomacromolecular complexes (regarded as measuring devices) is the main
      precondition of enzyme operation and information transfer determining the steady
      non-equilibrium state of biosystems. The presence of an internal formal
      description inside a biosystem, expressed in genetic structures (developmental
      program), is a consequence of its quantum properties. Incompleteness of this
      formal description provides the possibility of the generation of new functional
      relations and interconnections inside the system. This is a logical precondition
      of an evolutionary process. The quantum mechanical uncertainty that underlies the
      appearance of bifurcations is considered to be the main physical foundation of
      complication and irreversible transformation of biosystems.

PMID- 8286708
TI  - The hemodialysis prescription and quality-adjusted life expectancy. Renal
      Physicians Association Working Committee on Clinical Guidelines.
AB  - What comprises an optimal prescription for uremictoxin clearance in the chronic
      hemodialysis setting is a much disputed issue. The dispute is underscored by the
      rise in mortality of the U.S. dialysis population during the 1980s and reports of
      significant noncompliance with minimal treatment standards recommended from the
      National Cooperative Dialysis Study. A decision model was developed to summarize
      and test assumptions about the effect of various dialytic-treatment options on
      patient outcomes. Treatment options included delivered fractional urea clearance
      (Kt/V), dialysis-treatment duration, dialysis membrane (high flux versus
      conventional), dialysate (bicarbonate versus acetate), and ultrafiltration
      (controlled versus uncontrolled). The expected outcome for any set of treatment
      options was calculated as a function of a representative patient's life
      expectancy, adjusted for the probability and assumed importance of avoiding
      uremia- and treatment-related complications, referred to as quality-adjusted life
      expectancy (QALE). QALE increased by 59 days for each 0.1-U increase in Kt/V and
      by 187 days with high-flux dialysis. Controlled ultrafiltration with bicarbonate
      dialysis increased QALE by 30 days compared with uncontrolled ultrafiltration
      with acetate dialysis. Sensitivity analyses showed that, under conservative
      assumptions, QALE increased 11 days for every 0.1 increment in Kt/V. The model
      afforded a framework for reviewing the literature and testing assumptions about
      the expected benefits of dialytic-treatment options for the development of a
      clinical guideline on the adequacy of dialysis.

PMID- 8286709
TI  - The hemodialysis prescription and cost effectiveness. Renal Physicians
      Association Working Committee on Clinical Guidelines.
AB  - Case-mix adjusted mortality rates for patients undergoing hemodialysis for ESRD
      increased during the 1980s, despite the introduction of advanced dialysis
      technologies. Variations in dialysis practices suggest that excess mortality may
      be caused by inadequate uremic-toxin clearances. Cost-effectiveness analysis was
      used to assess whether attempts to improve uremic-toxin clearance are cost
      effective, assuming that these therapies are clinically effective. The medical
      literature was surveyed by the use of MEDLINE to assess the likelihood of
      clinical outcomes on the basis of the type of treatment given to the patient.
      Options considered in the model were delivered fractional urea clearance (Kt/V),
      dialysis-treatment duration, type of dialyzer membrane, dialysate, and
      ultrafiltration. Clinical outcomes included in the model were survival, severity
      of uremic symptoms, hospital days per year, and intradialytic hypotension and
      symptoms. Lifetime costs were calculated from data collected from a northern
      California dialysis center and abstracted from the literature. In the base-case
      scenario, it was assumed that increasing Kt/V to levels greater than 1 was
      effective in reducing morbidity and mortality. Under these assumptions,
      outpatient cost increased significantly, but the cost effectiveness of Kt/V equal
      to 1.5 was less than $50,000 per quality-adjusted life-year saved. These
      calculations indicate that, if higher levels of Kt/V prove clinically effective,
      they are also cost effective.

PMID- 8286710
TI  - Social support and subsequent mortality among patients with end-stage renal
      disease.
AB  - The association between social support in newly entered dialysis patients and
      their subsequent risk of mortality was investigated. Two hundred forty-nine
      dialysis patients were enrolled from dialysis facilities in two southeastern
      states. A score was calculated for the amount of social support a patient
      reported giving and receiving from spouse, family, friends, nurses, physicians,
      staff, and fellow patients. Patients were monitored for 12 months after
      enrollment into the cohort: 43 (17.6%) died. Mean (SD) scores for giving support
      to the family were higher among survivors, 3.59 (0.92), than among those who
      died, 3.17 (1.32) (P = 0.022). Mean scores for giving support to friends were
      also higher among survivors, 3.38 (1.13), than among nonsurvivors, 2.94 (1.33) (P
      = 0.044). After other factors associated with increased risk of dying, including
      age, sex, race, diabetic renal disease, angina pectoris, and functional status,
      were controlled for, individuals in the lowest quartile of giving social support
      to friends continued to have a greater risk of dying, with adjusted relative risk
      (95% confidence interval) = 2.02 (1.01, 4.07). In contrast, there were no
      differences in risk of death found for differing levels of receiving social
      support. It was concluded that social support is an independent risk factor for
      mortality among new dialysis patients.

PMID- 8286711
TI  - Effect of uric acid on plasma levels of 1,25(OH)2D in renal failure.
AB  - Previous studies from these laboratories have demonstrated that uremic biologic
      fluids contain substances that suppress 1,25(OH)2D metabolism. Among these
      substances, it was found that uric acid suppresses 1 alpha-hydroxylase activity
      and synthesis of 1,25(OH)2D in rats. In this study, the effect of uric acid on
      plasma concentrations of 1,25(OH)2D in patients with renal failure was examined.
      Nine patients with stable chronic renal failure (serum creatinine, 1.9 to 6.4
      mg/dL) were studied. None of the patients received vitamin D supplementation.
      Plasma concentrations of Ca, P, parathyroid hormone, creatinine, uric acid,
      1,25(OH)2D, and 25(OH)D were measured before and 1 wk after the patients received
      allopurinol, 300 mg daily. Plasma creatinine, Ca, P, parathyroid hormone, and
      25(OH)D did not change before or after allopurinol treatment. However, plasma
      uric acid decreased significantly from 7.3 +/- 0.4 to 4.0 +/- 0.4 mg/dL (P <
      0.01) and plasma concentration of 1,25(OH)2D rose from 30.8 +/- 2.7 to 38.2 +/-
      4.8 pg/mL (P < 0.01) after the ingestion of allopurinol. Allopurinol itself did
      not appear to directly enhance 1 alpha-hydroxylase activity in rats. It was
      concluded that a short-term administration of allopurinol suppresses plasmic uric
      acid and increases plasma 1,25(OH)2D in patients with chronic mild to moderate
      renal failure.

PMID- 8286712
TI  - L-arginine administration prevents glomerular hyperfiltration and decreases
      proteinuria in diabetic rats.
AB  - The effect(s) of L-arginine administration on the renal function of rats with
      untreated diabetes mellitus was examined. Rats received streptozotocin (N = 11)
      or vehicle (N = 12): Group 1 (normal rats, N = 6) drank tap water; Group 2
      (normal rats, N = 6) drank tap water containing 1% L-arginine; Group 3 (diabetic
      rats, N = 5) drank tap water; and Group 4 (diabetic rats, N = 6) drank tap water
      with 1% L-arginine. Rats were fed a standard rat chow diet (22.8% protein, 142% L
      arginine) with free access to food and water for 14 wk. Diabetic rats gained less
      weight, had significantly lower plasma levels of albumin and L-arginine, and had
      greater values for 24-h urine volumes and urine excretion of glucose, protein,
      urea, creatinine, nitrate, and nitrite than control rats. Diabetic rats given L
      arginine (Group 4) had significantly lower protein and cGMP excretion in the
      urine than did rats of Group 3. The administration of L-arginine did not affect
      the plasma levels of glucose or L-arginine in Groups 2 or 4 compared with those
      of their respective controls. Group 3 had significantly higher values for GFR
      than did the other three groups of rats, but values for effective RPF, mean
      arterial pressure, hematocrit, and renal vascular resistance were not
      significantly different between Groups 3 and 4. There was no significant
      difference in glomerular morphology among the four groups of rats as determined
      by light microscopy, and both groups of diabetic rats exhibited the Armanni
      Ebstein lesion in their tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286713
TI  - Contribution of angiotensin II to renal hemodynamic and excretory responses to
      nitric oxide synthesis inhibition in the rat.
AB  - This study was performed to evaluate the contribution of angiotensin II to the
      effects of nitric oxide (NO) synthesis inhibition on renal hemodynamics and
      excretory function in rats. Intravenous infusion of N omega-nitro-L-arginine
      (NLA; 20 micrograms/100 g.min) increased renal arterial pressure (RAP) from 128
      +/- 2 to 143 +/- 3 mm Hg (P < 0.05; N = 6) and decreased RBF by 64 +/- 3% (P <
      0.01) and GFR by 41 +/- 5% (P < 0.05). In response to reduction of RAP to control
      levels (127 +/- 2 mm Hg) by means of an adjustable clamp (CL) placed on the
      suprarenal aorta, RBF and GFR exhibited efficient autoregulation and were not
      altered. In rats (N = 6) pretreated with the AT1 angiotensin II receptor
      antagonist losartan (10 mg/kg iv), the infusion of NLA increased RAP (from 114 +/
      1 to 135 +/- 2 mm Hg; P < 0.05) and decreased RBF by 42 +/- 3% (P < 0.05).
      However, NLA did not decrease GFR in the losartan-treated rats. As in the control
      rats, the reduction of RAP to 113 +/- 1 mm Hg elicited autoregulatory responses
      that maintained RBF and GFR. In the untreated rats, at similar RAP (128 +/- 2
      (control) versus 127 +/- 2 mm Hg (NLA+CL)). NO synthesis inhibition decreased
      urine flow and sodium excretion (P < 0.05, in both cases). However, during
      blockade of AT1 receptors, NLA infusion failed to decrease urine flow and sodium
      excretion, even when RAP was controlled (114 +/- 1 (control) versus 113 +/- 1 mm
      Hg (NLA+CL)).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286714
TI  - Role of renin isoelectric heterogeneity in renal storage and secretion of renin.
AB  - Renin is a glycoprotein that is heterogeneous with respect to carbohydrate
      content and net charge. In an attempt to clarify the role of renin isoelectric
      heterogeneity in renal renin storage and secretion, the isoelectric profile of
      renal renin, secreted renin, and circulating renin were directly assessed and
      compared under basal and stimulated conditions by the use of an in vivo blood
      perfused rabbit kidney preparation. Under basal conditions, the kidney
      preferentially stored and secreted the relatively basic isoelectric forms of
      renin. Acute stimulation of renin secretion (reduced renal perfusion pressure and
      angiotensin-converting enzyme inhibition) significantly increased the secretion
      of the relatively basic isoelectric forms but had very little effect on the
      secretion of the relatively acidic renin forms. Circulating renin was composed
      primarily of relatively basic forms, which increased disproportionately after
      stimulation of renin secretion. These findings suggest that the isoelectric
      heterogeneity of renin is important in the cellular processing of renin and can
      be explained by a two-pool model in which the relatively acidic isoelectric forms
      of renin are constitutively secreted (and not stored) and the relatively basic
      isoelectric forms represent a regulated pathway in which they are stored and
      rapidly released in response to acute secretory stimuli. Preferential hepatic
      extraction of the more basic isoelectric forms has previously been described.
      Data from this study suggest that the disproportionate increase in circulating
      basic forms of renin observed after acute stimulation reflects the net effect of
      preferential renal the more basic renin isoelectric forms. The disproportionate
      increase in relatively basic circulating renin forms after acute secretory
      stimulation results in an overall circulating renin activity with a shorter half
      life.

PMID- 8286715
TI  - Impaired urinary ammonium excretion in patients with isolated proximal renal
      tubular acidosis.
AB  - During previous studies in patients with isolated proximal renal tubular acidosis
      (pRTA), the rates of urinary ammonium excretion were considered inappropriately
      low for their state of chronic metabolic acidosis. These observations were made
      while the patients were on a normal diet as well as when they were undergoing a
      short ammonium chloride test. Because these findings suggested an impaired
      ability to excrete maximal amounts of ammonium, the response to the 3-day acid
      loading test was evaluated in eight patients with isolated pRTA and in 10 normal
      control subjects. Plasma creatinine, acid-base, and electrolyte values were
      analyzed before and after 3 days of ingesting 2 mmol/kg.24 h of ammonium
      chloride. Twenty-four-hour urine specimens were collected the day before and on
      the third day of acid loading to determine urine pH, as well as the rate of
      excretion of NH4+ and titratable acid in milliequivalents per 24 h per 1.73 m2.
      During the basal state, all patients with pRTA had hyperchloremic metabolic
      acidosis and they excreted urine of lower pH (5.51 +/- 0.18 versus 6.00 +/- 0.13;
      P < 0.05) and greater titratable acid (29.1 +/- 4.3 versus 21.8 +/- 1.4; P <
      0.05); however, they had rates of NH4+ excretion similar to those of controls. On
      the third day of acid loading, they excreted urine of lower pH (4.66 +/- 0.03
      versus 5.00 +/- 0.03; P < 0.05) and equivalent amounts of titratable acid,
      whereas their NH4+ excretion was significantly less than that of controls (47.7
      +/- 4.4 versus 76.3 +/- 5.7; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286716
TI  - Role of protein kinase C in the adaptive increase in Na-H antiporter in
      respiratory acidosis.
AB  - Chronic respiratory acidosis stimulates the Vmax of the renal brush border Na-H
      antiporter. The activation of protein kinase C (PKC) by phorbol esters stimulates
      the activity of the renal Na-H antiporter. In this study, the hypothesis that PKC
      plays a role in the adaptive increase of the renal brush border Na-H antiporter
      activity to respiratory acidosis was tested. In vivo respiratory acidosis was
      associated with an increase in in vitro Na-H antiporter activity and also with an
      increase in brush border membrane PKC activity, without changes in PKC activity
      in cytosol or basolateral membranes. Na-H antiporter activity, assessed as the
      amiloride-sensitive component of 22Na uptake, was measured in cultured proximal
      tubule cells exposed to 10% CO2 for 48 h. Na-H antiporter activity was
      significantly higher in cells exposed to 10% CO2 than in those exposed to 5% CO2.
      To evaluate the role of PKC, cultured cells were depleted of PKC by exposure to
      the active phorbol ester phorbol 12-myristate 13-acetate (PMA; 10(-7) or 10(-6)
      M) for 48 h before exposure to 10% CO2. In the presence of 10% CO2, Na-H
      antiporter activity was significantly lower in PKC-depleted cells than in
      control. In addition, sphingosine, an inhibitor of PKC, also prevented the
      adaptation of the Na-H antiporter to 10% CO2 as compared with 5% CO2. In cells
      treated with the inactive analog 4 alpha-PMA, 22Na uptake was not different than
      that in control. PMA-treated cells also had a decrease in Na-H antiporter
      activity during exposure to 5% CO2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286717
TI  - The concept of preload and afterload applied to renal hemodynamics.

PMID- 8286718
TI  - The mammalian Na+/H+ exchanger gene family--initial structure/function studies.
AB  - A gene family of mammalian Na+/H+ exchangers has been identified. Three isoforms
      have been cloned, sequenced, and stably expressed, and structure/function studies
      have been begun. Several of the isoforms are found in the epithelia, and one of
      them is epithelial specific.

PMID- 8286719
TI  - CD45 and the immune response.
AB  - CD45 is a major transmembrane glycoprotein expressed on all nucleated
      hematopoietic cells. Eight isoforms of CD45 are distributed through the immune
      system according to cell type and degree of cellular differentiation.
      Heterogeneity among the isoforms is found entirely in the extracellular domain,
      arising from the differential splicing of up to four exons of a single gene. The
      control of isoform expression suggests that the extracellular domain may
      participate in protein-protein interactions with isoform-specific ligands. The
      intracellular domain of CD45 is large (approximately 700 amino acids), identical
      for all isoforms, and highly conserved across species. Two nonidentical
      intracellular sequences of about 240 amino acids that are homologous with a
      tyrosine phosphatase consensus sequence have been identified. Studies with
      purified CD45 have shown that all isoforms possess enzymatic activity in in vitro
      assays. In several T and B cell lines and in natural killer cells, it appears
      that CD45 is required for optimal signal transduction after stimulation through a
      number of surface receptors. Although an in vivo substrate has not been
      identified conclusively, one model suggests that CD45 functions to
      dephosphorylate a negative-regulatory tyrosine residue on one or more protein
      tyrosine kinases involved in receptor-mediated second messenger formation. In T
      cells, the src family kinases, lck and fyn, are candidates for this regulated
      kinase. In this review, some of the structural and functional aspects of CD45 and
      its role in signal transduction in the immune system are discussed.

PMID- 8286720
TI  - Preservation of vascular access.
AB  - Preservation of vascular access is critical in the long-term successful
      management of hemodialysis patients. Dialysis access abnormalities are the most
      common cause of hospitalization in this patient group, and access problems can
      increase the morbidity and cost involved in the care of these patients. Native
      fistulas are preferable to synthetic grafts because of longer survival and a
      lower complication rate. Venous outflow stenosis is the most common site of
      obstruction in a failing graft. The pathophysiology of access failure is poorly
      understood, but it seems to be related to intimal hyperplasia in the native
      vessel downstream from the anastomosis. The stimulation of local growth factors
      by needle puncture may also play a role. An assessment of access adequacy
      includes careful physical examination, laboratory evaluation, and ultimately,
      angiography. Measurements of recirculation and venous pressure are commonly used
      to screen for access dysfunction, and their appropriate use will lower the
      incidence of graft loss in dialysis units. Treatment is usually either
      angioplasty or surgery, with some centers having success with thrombolytic
      therapy. New techniques such as atherectomy and stent placement may prove to be
      beneficial, but this requires further study.

PMID- 8286721
TI  - Poiseuille Medial Award lecture: from papermaking fibers to human blood cells.

PMID- 8286722
TI  - Structure and rheology of gelatin and collagen gels.
AB  - This paper undertakes a parallel analysis of the gelation mechanisms, structure
      and rheological properties of gelatin and collagen gels. Although the molecular
      compositions of collagen and gelatin are almost identical, gelation proceeds from
      distinct mechanisms and leads to different types of molecular assemblies. First
      are presented the properties of the solutions, based on their structural and
      rheological characterization; then the mechanisms of gelation in the networks,
      observed by Transmission Electron Microscopy, of three types of gels: gelatin
      gels, Type I collagen gels and gels made of cuticle collagen extracted from
      annelid worms. The rheological investigation of the sol-gel transition of gelatin
      is described within the context of the theories of percolation and scaling laws.
      Different experimental approaches to the kinetics of gelation are presented,
      combining dynamic light scattering and rheology in respect to gelatin gels.

PMID- 8286723
TI  - Rheological properties of casein micelle gels: the influence of calcium
      concentration on gelation induced by rennet.
AB  - Rheological studies on the gelation of casein micelles using rennet have been
      performed in relation to cheese making. The influence of calcium concentration on
      the time course of storage and loss modulus was investigated using rheological
      measurements. Observed gelation curves at 30 degrees C were well approximated by
      first-order reaction kinetics except for the very short time after gelation
      occurred. The saturated modulus decreased with decreasing calcium ion
      concentration in the range from 4.5 to 9 mM. The rate constant of gelation, Kg
      decreased linearly with decreasing calcium ion concentration. A minimum amount of
      calcium was needed for gelation to occur. Kg was inversely proportional to the
      latent time, tL. The value of the product of Kg and tL for the casein micelle
      gels containing various calcium concentrations was 0.4.

PMID- 8286724
TI  - Polysaccharide strong and weak gels.
AB  - Small deformation oscillatory shear measurements have enabled a distinction to be
      made between so-called "strong" and "weak" gels, in particular those formed from
      biologically significant polysaccharides. At small enough strains, both systems
      give essentially the same mechanical spectrum, with G' > G", and with both moduli
      largely independent of frequency. However, the deformation dependence of the two
      classes of materials is very different. Strong gels are essentially strain
      independent (linearly viscoelastic) for strains of greater than about 0.25,
      whereas weak gels show such a response only for strains of less than about 0.05.
      At large deformations strong gels will rupture and fail, and will never "heal"
      without melting and resetting. Conversely, weak gels will recover and can flow
      without fracture, giving a power law response, with an exponent approaching -1,
      so-called "yield stress" behavior. The rheological properties of a strong gel,
      agarose, derived from the Rhodophyceae (marine algae) and a weak gel xanthan, an
      exocellular slime exuded by bacteria of the genus Xanthomonas, are measured in
      vitro, and related to in vivo requirements.

PMID- 8286725
TI  - Polysaccharide-protein interaction: a rheological study of the gel-sol transition
      of a gelatin-methylcellulose-water system.
AB  - Viscoelastic parameters for mixtures of gelatin and methylcellulose were measured
      as a function of temperature, in order to study the gel-sol transition of the
      system in which biopolymers forming thermo-setting and thermo-melting gels
      coexist. At higher temperatures than 45 degrees C, the gel network is mainly
      formed by methylcellulose while at lower temperatures around 5 degrees C, it is
      mainly formed by gelatin. At higher temperatures than 45 degrees C, gelatin
      inhibits the gelation of methylcellulose. A small amount of methylcellulose helps
      gelatin to form a network at lower temperatures. However, excessive amounts of
      methylcellulose inhibit the growth of network structure. Therefore, this mixture
      forms a phase separated gel at higher temperatures while it is not completely
      phase separated at lower temperatures, probably by some interaction between non
      substituted hydroxyl groups in methylcellulose with carboxylic groups in gelatin.

PMID- 8286726
TI  - A non-linear Maxwell model of biofluids: application to normal blood.
AB  - For transient shear stress responses at moderate shear rates, predictions of a
      Non-Linear Maxwell model, in which the viscosity coefficient is assumed to depend
      on the instantaneous structural state of the material, are compared to
      measurements on normal blood (McMillan et al., 1986). This is carried out on a
      modified viscometer which incorporates a dynamic balance torque monitoring, in
      order to eliminate apparatus inertia effects. Satisfactory agreement is obtained
      with model variables closely related to the structure kinetics.

PMID- 8286727
TI  - Study of biofluid mechanics at arterial bifurcations: importance of flow division
      ratio as a parameter.
AB  - We re-examined the measurement of the mass flow ratio at model bifurcations as a
      function of the inlet Reynolds number, which has been used to study the role of
      arterial bifurcation in distal blood supply. However, this relationship was found
      not to be applicable to investigations of blood circulation, because the measured
      mass flow ratio is strongly dependent on the resistance downstream of the
      bifurcation, and therefore is specific to the experimental set-up. An alternative
      approach for studying the role of arterial bifurcation is presented, in which the
      flow division ratio is used as a parameter.

PMID- 8286728
TI  - Impaired deformability of Heinz body-forming red cells.
AB  - Although a decrease in the deformability of red blood cells (RBCs) has been
      suspected in Heinz body-forming hemolytic anemia, it remains uncertain whether
      the formation of Heinz bodies themselves impairs RBC deformability or not. To
      elucidate this question, we used RBCs treated with phenylhydrazine and RBCs from
      patients with unstable hemoglobin (Hb) disease (Hb Yokohama) to investigate the
      effect of Heinz body formation on deformability in terms of RBC filterability
      through nickel mesh and viscosity of the RBC suspension. The phenylhydrazine
      treated RBCs exhibited a marked decrease in deformability in a dose-dependent
      manner. The Heinz body-forming RBCs from the patients also showed a marked
      decrease in deformability. Thus we confirmed that Heinz body formation impairs
      RBC deformability. Further, both phenylhydrazine-treated RBCs and RBCs from the
      patient showed a degradation of spectrin without any cross-linking of membrane
      proteins, thereby suggesting that the impaired deformability is associated with
      the oxidative degradation of the cytoskeletal framework. In summary, this study
      supports the conclusion that RBC deformability is impaired by the presence of
      Heinz bodies as well as the related oxidative damage involved in their formation.

PMID- 8286729
TI  - Hemodynamics in rigid and distensible saccular aneurysms: a numerical study of
      pulsatile flow characteristics.
AB  - Flow characteristics are examined in two lateral model aneurysms by means of
      numerical simulation. The study concentrates on basic flow and stress patterns in
      a rigid wall and in a distensible wall aneurysm. The numerical solution of the
      governing Navier-Stokes equations describing incompressible, pulsatile, three
      dimensional non-Newtonian flow is accomplished with the use of a finite element
      method together with a pressure correction technique. The inflow into the
      aneurysm is seen to arise from the downstream lip of the orifice and to be
      directed backward to the center. Backflow to the parent vessel takes place along
      the walls of the aneurysm. The intra-aneurysmal flow is found to be low compared
      with the flow velocity in the parent vessel, and even stagnation of flow occurs
      in the dome of the aneurysm. With a distensible wall, the basic flow
      characteristics are changed during systolic flow. The intra-aneurysmal secondary
      flow increases significantly. The increase and decrease of the flow velocity at
      the downstream lip reflect the expansion and contraction of the aneurysm wall
      where the maximal wall displacement during systolic acceleration is about 6% of
      the aneurysm diameter.

PMID- 8286730
TI  - Immunotoxins: will their clinical promise be fulfilled?

PMID- 8286731
TI  - Controversies in the management of early stage Hodgkin's disease.

PMID- 8286732
TI  - The der(11)-encoded MLL/AF-4 fusion transcript is consistently detected in
      t(4;11)(q21;q23)-containing acute lymphoblastic leukemia.
AB  - The t(4;11)(q21;q23) is the most common translocation involving band 11q23 and is
      found predominantly in acute lymphoblastic leukemias (ALLs) of infants. Recent
      studies have shown that this translocation involves the MLL gene on chromosome 11
      and the AF-4 gene on chromosome 4. Using oligonucleotide primers derived from
      these genes, we established reverse transcription-polymerase chain reaction (RT
      PCR) assays for the detection of the fusion transcripts from both the der(11) and
      der(4) chromosomes. Using these assays we analyzed 23 pediatric cases of t(4;11)
      containing ALL. RT-PCR analysis for the der(11)-derived MLL/AF-4 fusion
      transcript resulted in its detection in every case at a sensitivity of greater
      than 1 leukemic cell in 10(5) cells. Sequence analysis of MLL/AF-4 PCR products
      demonstrated fusion mRNAs resulting from breaks in MLL introns 6, 7, or 8, with
      alternative splicing to one of three exons in the AF-4 gene. In contrast,
      analysis for the der(4)-derived transcript resulted in the detection of this
      chimeric mRNA in only 84% of the cases analyzed. These data suggest that the
      critical chimeric gene product involved in the establishment of the leukemic
      clone is derived from the der(11) chromosome. Moreover, these data demonstrate
      the utility of the RT-PCR assay for the der(11)-encoded message both for
      diagnosing t(4;11)-containing leukemia and for monitoring patients for minimal
      residual disease.

PMID- 8286733
TI  - Long-term bone marrow culture in persons with Fanconi anemia and bone marrow
      failure.
AB  - Fanconi anemia is an autosomal recessive disease characterized by a high risk of
      developing bone marrow (BM) failure and acute myelogenous leukemia. We studied
      growth of hematopoietic progenitor cells in long-term BM culture (LTBMC) in 8
      persons with Fanconi anemia and BM failure. Although LTBMC were initiated with
      very few BM cells, an adherent layer formed in cultures from 7 persons. In these
      cultures, the number of nonadherent cells increased for 10 to 15 days. Cell
      growth continued until cultures were terminated at day 35 to 40. During the first
      2 weeks of culture, most nonadherent cells were differentiated myeloid cells. By
      days 35 to 40, the adherent layer contained cells able to initiate secondary
      LTBMCs. These data indicate that hematopoietic precursors cells able to
      proliferate and differentiate in vitro are present in the BM of persons with
      Fanconi anemia and BM failure. They suggest that mechanisms other than absent
      precursor cells are responsible for BM failure in Fanconi anemia.

PMID- 8286734
TI  - Search for maternal cells in human umbilical cord blood by polymerase chain
      reaction amplification of two minisatellite sequences.
AB  - Since our first report in 1989, 26 transplants by means of umbilical cord blood
      have been reported. Furthermore, systematic studies of the feasibility of using
      banked placental blood for bone marrow reconstitution of unrelated recipients on
      a large scale are in progress worldwide. However, already by 1989, it was pointed
      out that the use of cord blood might be hampered by contamination of neonatal
      blood with maternal cells contributing unacceptably to graft-versus-host disease
      (GVHD). In the present study, we used the polymerase chain reaction (PCR)
      amplification of 2 minisatellite sequences (33.6 and MS 51) to address this
      question. The sensitivity of PCR amplification of minisatellite sequences is
      known to be of 1% to 0.1%. This sensitivity has been confirmed in the present
      study, in which a dilution analysis was performed for each experiment in which
      cell separation was performed. The inclusion of the dilution experiment in these
      analyses allowed us to estimate the relative amount of contaminating maternal
      cells, if any. Among 47 cases (31 whole blood analyses, 10 gradient separations,
      and 6 subpopulation separations), the coamplification of the 2 minisatellites
      sequences allowed the discrimination of maternal and neonate alleles in 42 cases
      (89%). In 1 case, we were able to detect a child-specific allele in a mother's
      whole blood sample, thus validating our approach to search for maternal cells in
      cord blood. In a single other case, we were able to detect a maternal-specific
      allele in the cord blood sample. This maternal specific allele was detected in
      the whole blood, polymorphonuclear cell, and lymphocyte fractions. Comparison of
      the signal intensity obtained with these 3 cord blood samples to the result of
      the dilution experiment performed in the same analysis led to an estimate of 1 to
      5% maternal cells in the polymorphonuclear cell fraction and 0.1% to 1% maternal
      cells in the whole blood and lymphocyte cell fractions. In conclusion, our study
      indicates that maternal cells are very rarely present in the cord blood collected
      at birth because we detected them in only 1 of 47 cases. More importantly, when
      detected, they were present at very low level in the lymphocyte cell fraction
      (0.1% to 1%). However, although small, this amount of cells may result in GVHD in
      a susceptible recipient. Because the method we used allows the detection of
      maternal cells within cord blood from 10(4) nucleated cells, it would thus be of
      interest in a cord blood banking perspective.

PMID- 8286735
TI  - Platelets inhibit fibrinolysis in vitro by both plasminogen activator inhibitor-1
      dependent and -independent mechanisms.
AB  - Platelet-rich thrombi are resistant to lysis by tissue-type plasminogen activator
      (t-PA). Although platelet alpha-granules contain plasminogen activator inhibitor
      1 (PAI-1), a fast-acting inhibitor of t-PA, the contribution of PAI-1 to the
      antifibrinolytic effect of platelets has remained a subject of controversy. We
      recently reported a patient with a homozygous mutation within the PAI-1 gene that
      results in complete loss of PAI-1 expression. Platelets from this individual
      constitute a unique reagent with which to probe the role of platelet PAI-1 in the
      regulation of fibrinolysis. The effects of PAI-1-deficient platelets were
      compared with those of normal platelets in an in vitro clot lysis assay. Although
      the incorporation of PAI-1-deficient platelets into clots resulted in a moderate
      inhibition of t-PA-mediated fibrinolysis, normal platelets markedly inhibited
      clot lysis under the same conditions. However, no difference between PAI-1
      deficient platelets and platelets with normal PAI-1 content was observed when
      streptokinase or a PAI-1-resistant t-PA mutant were used to initiate
      fibrinolysis. In addition, PAI-1-resistant t-PA was significantly more efficient
      in lysing clots containing normal platelets than wild-type t-PA. We conclude that
      platelets inhibit t-PA-mediated fibrinolysis by both PAI-1-dependent and PAI-1
      independent mechanisms. These results have important implications for the role of
      PAI-1 in the resistance of platelet-rich thrombi to lysis in vivo.

PMID- 8286736
TI  - A phase I/II study of sequential interleukin-3 and granulocyte-macrophage colony
      stimulating factor in myelodysplastic syndromes.
AB  - In this phase I/II study, 9 patients with myelodysplastic syndromes (MDS) were
      treated with interleukin-3 (IL-3) followed by granulocyte-macrophage colony
      stimulating factor (GM-CSF). Each treatment cycle was 28 days long and
      administered as follows: 1 microgram/kg/d IL-3 on days 1 through 7 and 3
      micrograms/kg/d GM-CSF for days 8 through 21, followed by a 7-day rest period. IL
      3 dose escalations were planned, but the dose of GM-CSF was fixed. Three patients
      had refractory anemia, 4 had refractory anemia with ringed sideroblasts, and 2
      had refractory anemia with excess blasts. Six patients were dependent on red
      blood cell transfusions, 1 on platelet transfusions, and 2 on both. The absolute
      neutrophil count improved in 7 (77%) patients and the platelet count improved in
      3 (33%) patients during therapy. Hemoglobin levels were unchanged. A clinically
      relevant response was seen in only 1 patient with thrombocytopenia, and he
      received five cycles of therapy. The neutrophil count decreased in 2 patients and
      the platelet count decreased in 4 patients during treatment. The toxicity of the
      treatment was significant. In the first cohort of 3 patients, 1 patient developed
      supraventricular tachycardia and congestive heart failure. In the second group, 1
      patient developed progressive granulocytopenia and died of gram-negative
      septicemia. Because of the disparate toxicity, 3 more patients were treated at
      the same dose level. One of these experienced a high fever and bone pain
      requiring hospitalization. Because of these adverse effects, the IL-3 dose was
      not escalated and all patients received 1 microgram/kg/d for 7 days. We believe
      that sequential therapy with IL-3 and GM-CSF at these dose levels causes
      unacceptable toxicity in patients with MDS. The major toxic events occurred
      during weeks 4 and 5 after starting treatment and may have been primarily caused
      by GM-CSF therapy. Although neutrophil counts improve in most patients, the
      effect on red blood cells and platelets is minimal. At present, this form of
      therapy remains problematic and appears to have a limited potential in the
      management of MDS.

PMID- 8286737
TI  - Human cytomegalovirus alters interleukin-6 production by endothelial cells.
AB  - In an effort to study whether human cytomegalovirus (HCMV) can disrupt the
      balanced cytokine network that controls human hematopoiesis, we investigated the
      ability of a laboratory strain HCMV (AD169) to alter the production of
      interleukin-6 (IL-6) by cultured endothelial cells (HUVECs). ECs are important
      components of human bone marrow stroma and produce factors that stimulate the
      proliferation and differentiation of human hematopoietic progenitors. HCMV was
      able to greatly increase production of both mRNA and protein for IL-6 in unprimed
      HUVECs. When we discriminated between viral pellet and cleared viral
      supernatants, the supernatants induced an increase in mRNA at 30 minutes and
      protein by 2 hours, whereas an increase in IL-6 caused by virus itself did not
      become evident until 12 hours. The possibility that IL-6 induction was simply
      caused by the presence in the viral stock of endotoxin, IL-1 alpha, IL-1 beta,
      tumor necrosis factor alpha, or IL-4, all known inducers of IL-6 in HUVECs, was
      ruled out by the addition of polymyxin B and appropriate neutralizing antibodies.
      These findings show that HCMV is capable of directly and indirectly modulating
      the production by HUVECs of IL-6, one of the cytokines involved in the process of
      hematopoiesis.

PMID- 8286738
TI  - Administration of recombinant human interleukin-7 to mice induces the exportation
      of myeloid progenitor cells from the bone marrow to peripheral sites.
AB  - The administration of recombinant human interleukin-7 (rhIL-7) to mice twice a
      day for 7 days does not appreciably change bone marrow (BM) cellularity, but does
      result in a threefold to fivefold increase in the total number of leukocytes in
      the spleen, an eightfold to 10-fold increase in the total number of
      nonparenchymal cells (NPC) obtained from the liver, and up to a 20-fold increase
      in the total number of peripheral white blood cells (WBC). This regimen of rhIL-7
      administration also causes a profound reduction in the total number of
      progenitors in the BM for both single-lineage colony-forming units-culture (CFU
      c) (> 90%) and multilineage CFU-granulocyte, erythroid, monocyte, megakaryocyte
      (CFU-GEMM) (> 99%) colonies. In contrast, mice treated with rhIL-7 exhibited
      increases in both CFU-c (20- to 40-fold, 20-fold, and 15- to 40-fold) and CFU
      GEMM (8- to 10-fold, 30-fold, and 6- to 10-fold) cultured from the peripheral
      blood, spleen, and NPC, respectively. The increase in CFU in the NPC was
      accompanied by a fivefold increase in the number of MAC-1+ cells and a ninefold
      increase in the number of 8C5bright+ cells. Splenectomy of mice before the
      administration of rhIL-7 further increased the total number of WBC, NPC, and
      myeloid progenitors as compared with the rhIL-7-treated nonsplenectomized mice.
      Finally, selective depletion of the BM by intraperitoneal administration of 89Sr
      (98% reduction in BM cellularity and > 99% reduction in BM myeloid progenitors)
      abrogated the rhIL-7-induced increases in cellularity and myeloid progenitor
      number in the peripheral blood, spleen, and NPC. These results show that the
      changes in myelopoiesis observed after in vivo administration of rhIL-7 to mice
      result largely from the emigration of myeloid progenitors from the BM through the
      blood to the spleen, liver, and, possibly, other peripheral organs.

PMID- 8286739
TI  - Increased endogenous thrombin generation in children with acute lymphoblastic
      leukemia: risk of thrombotic complications in L'Asparaginase-induced antithrombin
      III deficiency.
AB  - Pediatric patients with acute lymphoblastic leukemia (ALL) are at an increased
      risk of thromboembolic events. Potential responsible mechanisms include the
      disease process itself, treatment with chemotherapeutic agents (particularly L
      Asparaginase [ASP]), or a combination of the disease and treatment. We studied
      thrombin regulation in 26 consecutive children with ALL and 14 healthy age
      matched controls by: (1) plasma concentrations of prothrombin; (2) plasma
      inhibition of 125I-alpha-thrombin; and (3) four biochemical markers of in vivo
      thrombin activation (thrombin complexed to its inhibitor antithrombin III [ATIII;
      TAT], prothrombin fragment 1.2 (F1.2), activated protein C complexed to the
      inhibitors alpha 1 antitrypsin [APCAT]), and protein C inhibitor (APC-PCI).
      Measurements were made at presentation before treatment, after treatment with ASP
      alone, and during combination chemotherapy with and without ASP. At presentation,
      the capacity to generate thrombin (reflected by plasma prothrombin
      concentrations) and the capacity to inhibit thrombin (125I-alpha-thrombin-
      inhibitor complex formation) were similar in children with ALL compared with that
      for healthy children. After ASP alone or as part of combination chemotherapy,
      prothrombin levels were preserved, whereas plasma inhibition of 125I-alpha
      thrombin decreased significantly because of a decrease in plasma concentrations
      of inhibitors, most importantly ATIII. After combination chemotherapy without
      ASP, plasma concentrations of ATIII and the capacity to inhibit 125I-alpha
      thrombin returned to normal values, whereas prothrombin levels increased above
      control values. Thrombin generation in vivo also differed from healthy controls.
      At presentation, plasma concentrations of three of four markers of in vivo
      thrombin activity (TAT, F1.2, APCAT, but not APC-PCI) were increased in children
      with ALL. Neither ASP alone nor combination chemotherapy with or without ASP
      significantly altered values of these three markers. In summary, although the in
      vitro capacity to generate thrombin was preserved, the in vitro capacity to
      inhibit 125I-alpha-thrombin decreased after ASP therapy. Evidence for increased
      endogenous thrombin generation was documented in children with ALL at
      presentation and throughout treatment. We speculate that poor regulation of this
      thrombin may contribute to thrombotic complications in children with ALL.

PMID- 8286740
TI  - Structural changes in platelet glycoprotein IIb/IIIa by plasmin: determinants and
      functional consequences.
AB  - Plasmin exposure modulates platelet aggregation responses, but a direct effect of
      plasmin on the platelet fibrinogen receptor, glycoprotein IIb/IIIa (GPIIb/IIIa),
      has never been conclusively shown in a plasma milieu. To examine this issue, we
      incubated platelets in platelet-rich plasma with plasmin and measured the effect
      of this treatment on platelet aggregation, fibrinogen binding, and the structural
      integrity of GPIIb/IIIa. Plasmin treatment reduced maximal reversible fibrinogen
      binding in a dose-dependent fashion, and this reduction in binding was
      accompanied by a correlative reduction in the maximal rate of aggregation.
      Immunoblots performed with polyclonal antibodies against GPIIb/IIIa showed that
      GPIIIa had been cleaved by plasmin, but this cleavage was detected only after
      subsequent degradation of the solubilized GPIIb/IIIa with Staphylococcus aureus
      V8 (Glu-C) endoprotease. Peptide sequence analysis showed that cleavage occurred
      at the lys444-pro445 bond in the first cysteine-rich repeat domain of GPIIIa a
      unique proteolytic event observed only in the presence of plasma fibrinogen.
      These observations suggest that plasmin modifies GPIIIa by a unique proteolytic
      event in plasma that is dependent on fibrinogen binding and, consequently, is
      accompanied by significant reductions in fibrinogen binding and aggregation
      response.

PMID- 8286741
TI  - Recombinant immunotoxins containing anti-Tac(Fv) and derivatives of Pseudomonas
      exotoxin produce complete regression in mice of an interleukin-2 receptor
      expressing human carcinoma.
AB  - Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin composed of the
      variable domains of the monoclonal antibody anti-Tac, which binds to the p55
      subunit of the interleukin-2 receptor (IL-2R), and a truncated form of
      Pseudomonas exotoxin (PE), which does not bind to the PE receptor (Chaudhary et
      al, Nature 339:394, 1989). Whereas its cytotoxic activity toward autoimmune and
      malignant target cells has been established, its efficacy in vivo remains
      unknown. To establish an animal model, we produced ATAC-4 cells by transfecting
      the gene encoding the low-affinity IL-2R (p55) into A431 epidermoid carcinoma
      cells. ATAC-4 cells contained low-affinity IL-2Rs (2 x 10(5)/cell) and formed
      tumors in nude mice. In tissue culture, protein synthesis in ATAC-4 cells was
      inhibited 50% (IC50) at 0.06 ng/mL (0.9 pmol/L) of anti-Tac(Fv)-PE40. IC50s for
      the derivatives anti-Tac(Fv)-PE38, which is missing PE amino acids 365-380, and
      anti-Tac(Fv)-PE38KDEL, which contains the same deletion plus the KDEL carboxyl
      terminus, were 0.04 and 0.025 ng/mL, respectively. All the agents produced
      complete tumor regressions in ATAC-4 tumor-bearing mice and anti-Tac(Fv)-PE38KDEL
      had significant antitumor activity at 1% of the LD50. The dose limiting toxicity
      of anti-Tac(Fv)-PE38KDEL was from hemorrhagic liver necrosis, which was observed
      at approximately 55% of the LD50.

PMID- 8286742
TI  - Differential effects of anti-tumor necrosis factor monoclonal antibodies on
      systemic inflammatory responses in experimental endotoxemia in chimpanzees.
AB  - Tumor necrosis factor (TNF) is considered to be a pivotal mediator of endotoxin
      induced lethality. To assess the intermediate role of TNF in specific systemic
      inflammatory responses known to contribute to tissue injury in endotoxemia, eight
      healthy adult chimpanzees were intravenously injected with Escherichia coli
      endotoxin (4 ng/kg). In four of these animals the administration of endotoxin was
      followed immediately by a bolus intravenous injection of an anti-TNF monoclonal
      antibody (15 mg/kg). Treatment with anti-TNF completely prevented the endotoxin
      induced increase in serum TNF activity, and profoundly reduced the appearance of
      interleukin-6 and -8 (both P < .05). Neutrophilia and lymphopenia were not
      affected by anti-TNF, whereas neutrophil degranulation, as measured by the plasma
      concentrations of elastase-alpha 1-antitrypsin complexes, was only slightly
      reduced (peak levels after endotoxin alone 31.0 +/- 3.4 ng/mL, versus 25.5 +/-
      3.4 ng/mL after endotoxin with anti-TNF; P < .05). Anti-TNF did not influence
      endotoxin-induced activation of the coagulation system, as reflected by unchanged
      increases in the plasma concentrations of the prothrombin fragment F1 + 2 and
      thrombin-antithrombin III complexes. In contrast, anti-TNF strongly attenuated
      the activation of the fibrinolytic system, ie, peak plasma levels of plasmin
      alpha 2-antiplasmin were 33.8 +/- 11.1 nmol/L after endotoxin alone and 17.0 +/-
      2.9 nmol/L after endotoxin with anti-TNF (P < .05). These results suggest that
      TNF is not the common mediator of systemic inflammatory changes in low-grade
      endotoxemia. Moreover, the finding that in this mild model anti-TNF specifically
      inhibited fibrinolysis suggests that treatment with anti-TNF potentially may
      enhance the tendency towards microvascular thrombosis in sepsis.

PMID- 8286743
TI  - Alterations of p53 and c-myc in the clonal evolution of malignant lymphoma.
AB  - We derived the lymphoma cell lines OCI-Ly 13.1 and OCI-Ly 13.2 from a patient
      with non-Hodgkin's lymphoma at the time of presentation and during chemotherapy
      resistant relapse. These lines were of T-cell phenotype and contained the
      identical T-cell receptor beta-chain rearrangement, indicating that both lines
      were members of the same malignant clone. The lines differed in their growth
      characteristics; OCI-Ly 13.1 grew slowly and required growth factors for colony
      formation, whereas OCI-Ly 13.2 grew rapidly and formed colonies without addition
      of growth factors. To test whether or not these biologic differences were
      associated with specific genetic changes, we evaluated the status of the c-myc
      and p53 genes of both cell lines. The p53 and c-myc genes of OCI-Ly 13.1 were in
      germline configuration and produced normal-sized transcripts. The p53 protein
      expressed in OCI-Ly 13.1 was recognized by the anti-p53 monoclonal antibody,
      PAb240, indicating a conformation typical of p53 proteins expressed by p53
      alleles containing a missense mutation. However, sequencing studies of the entire
      p53 coding region did not reveal any point mutations. In contrast, the cell line
      OCI-Ly 13.2 contained structural abnormalities of both the c-myc and p53 genes.
      In addition, one of the p53 alleles was lost as determined by a cDNA probe for
      the p53 gene (17p 13.1) and the YNZ22.1 probe (17p 13.3). These changes resulted
      in the absence of p53 protein and mRNA in OCI-Ly 13.2 as detected by
      immunoprecipitation and Northern blot analysis, respectively. They may be a
      reflection of disease progression and may be associated with the altered behavior
      of the malignant cell population within the patient and in vitro.

PMID- 8286745
TI  - Successful treatment of disseminated human Hodgkin's disease in SCID mice with
      deglycosylated ricin A-chain immunotoxins.
AB  - To evaluate the effects of deglycosylated ricin A-chain (dgA) immunotoxins
      against disseminated Hodgkin's lymphoma, we used RFT5.dgA (CD25) and IRac.dgA (70
      kD) to treat L540Cy Hodgkin cells in severely immunodeficient SCID mice. In this
      model, more than 90% of the animals developed multiple lymphomas in various
      organs such as the lymph nodes, liver, bone marrow, and extranodal sites that
      killed untreated animals after a mean survival time (MST) of 36.3 days. A single
      intraperitoneal injection of 8 micrograms of either immunotoxin rendered 95%
      (RFT5.dgA) and 93% (IRac.dgA), respectively, of mice tumor-free when applied 1
      day after tumor challenge. The MST of the RFT5.dgA-treated group was extended by
      more than 80 days (P < .00001). SCID mice treated 12 days after tumor challenge
      had lower remission rates (46%), suggesting that the antitumor effect of the
      immunotoxins depends on the number of tumor cells present. We conclude that ricin
      A-chain immunotoxins have potent antitumor effects against disseminated Hodgkin's
      tumors in SCID mice and that this model is ideally suited for the evaluation of
      different immunotoxin treatment modalities.

PMID- 8286744
TI  - Suppression of juvenile chronic myelogenous leukemia colony growth by interleukin
      1 receptor antagonist.
AB  - Bone marrow (BM) and peripheral blood (PB) cells from patients with juvenile
      chronic myelogenous leukemia (JCML) exhibit spontaneous in vitro proliferation.
      Several cytokines including granulocyte-macrophage colony-stimulating factor (GM
      CSF), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha)
      have been implicated in supporting the growth of leukemic monocyte-macrophage
      colonies either by autocrine or paracrine pathways. In seven untreated JCML
      patients, we investigated the role of IL-1 in the spontaneous growth of these
      cells by specifically blocking IL-1 receptors. The IL-1 receptor antagonist (IL-1
      Ra) was added to the clonogenic assays, and in each case significant (mean = 63%,
      range = 35% to 82%) inhibition of spontaneous proliferation was observed.
      Uncultured circulating cells from PB or BM of four out of five patients expressed
      IL-1 beta-specific mRNA and secreted the protein into the culture supernatants.
      Moreover, by means of reverse transcriptase-polymerase chain reaction (RT-PCR),
      we demonstrated that most of the spontaneously growing leukemic colony-forming
      unit cells (CFU-C) obtained from BM cells of two patients were positive for the
      presence of the IL-1 beta-specific mRNA. Despite the presence of a measurable
      amount of GM-CSF in JCML cell culture supernatants, GM-CSF-specific mRNA in CFU-C
      cells of four cases was not detected by RT-PCR. These data further support a
      central role for IL-1 beta in the pathogenesis of JCML and suggest that the use
      of IL-1 Ra could represent a novel therapeutic strategy against this disorder.

PMID- 8286746
TI  - All-trans retinoic acid reverses phorbol ester resistance in a human myeloid
      leukemia cell line.
AB  - Treatment of human HL-60 leukemic cells with 12-O-tetradecanoylphorbol-13-acetate
      (TPA) is associated with activation of protein kinase C (PKC) and induction of
      monocytic differentiation. An HL-60 variant cell line, termed HL-525, derived
      from long-term exposure to TPA (Homma et al, Proc Natl Acad Sci USA 83: 7316,
      1986) is resistant to TPA-induced differentiation and displays decreased PKC beta
      expression compared with the HL-60 parent line. However, this variant exhibits
      features of granulocytic differentiation, including nitroblue tetrazolium
      reduction, when exposed to all-trans retinoic acid (ATRA). Whereas treatment of
      HL-525 cells with ATRA or TPA alone had no effect on features of monocytic
      differentiation, these agents in combination resulted in cellular adhesion,
      nonspecific esterase staining, and induction of the c-fms (monocyte growth factor
      receptor) gene. In order to measure PKC expression associated with the reversal
      of TPA resistance by ATRA, we exposed HL-525 cells to ATRA and analyzed PKC-mRNA
      and protein levels. Exposure of HL-525 cells to ATRA for 3 days resulted in
      induction of PKC beta transcripts, whereas there was little change in PKC alpha
      mRNA levels. ATRA treatment was also associated with an increase in PKC activity
      and an induction of cytosolic PKC beta protein levels. These findings are
      consistent with the hypothesis that ATRA reverses TPA resistance in HL-525 cells
      by enhancing the expression of PKC.

PMID- 8286747
TI  - The bone marrow fibrosis of hairy-cell leukemia is caused by the synthesis and
      assembly of a fibronectin matrix by the hairy cells.
AB  - Hairy-cell leukemia (HCL) is a proliferation of clonal B-lymphocytes with
      features of activation. The disease has a number of distinctive characteristics,
      prominent among which is the fine reticulin fibrosis invariably present in the
      bone marrow. However, fibroblast infiltration has never been noted in the marrow
      and the origin of the fibrosis has not been established. The present studies show
      that the hairy cells (HCs) of HCL produce an insoluble matrix of fibronectin (FN)
      in vitro. FN synthesis was shown by the appearance of cellular FN on the surface
      of cells cultured in serum-free medium and by immunoprecipitation of the
      metabolically labeled protein from HC aggregates. Moreover, the HCs were shown to
      assemble FN into disulphide-bonded multimers. This assembly was blocked by a 70
      kD amino-terminal fragment of the molecule that blocks FN multimer formation by
      fibroblasts. HCs expressed abundant VLA-5, an FN receptor not present on normal
      circulating B lymphocytes, but important in matrix formation. Furthermore, HCs
      were shown to adhere to an FN fragment containing the VLA-5 binding site. It is
      therefore suggested that the VLA-5 of HCs is implicated in their assembly of FN
      matrix. The in vivo relevance of the findings was established by the
      demonstration of FN in association with infiltrating HCs in bone marrow sections
      from patients with HCL. It is concluded that the HCs synthesise and assemble an
      FN matrix and that this is at least partly responsible for the bone marrow
      fibrosis so characteristic of the disease.

PMID- 8286748
TI  - Cytogenetic findings in peripheral T-cell lymphomas as a basis for distinguishing
      low-grade and high-grade lymphomas.
AB  - Cytogenetic studies on lymph node and skin biopsy specimens and peripheral blood
      in 104 patients with peripheral T-cell lymphomas (PTL) were compared with
      histopathologic diagnoses made according to the updated Kiel classification. Low
      grade lymphomas presented normal metaphases more frequently than high-grade ones
      (P < .0001). This difference remained significant if cases with greater than 10%
      and greater than 50% normal metaphases in unstimulated cultures and in cultures
      stimulated by different mitogens were compared. On the other hand, high-grade
      lymphomas more often showed aberrant clones (P < .05), triploid to tetraploid
      clones (P < .0001), and complex clones with more than four chromosome changes (P
      < .01). Low-grade PTL showed consistent cytogenetic features. Clones with both
      inv(14)(q11q32.1) and trisomy 8q, mostly caused by i(8q)(q10), were found in all
      cases of T-cell chronic lymphocytic leukemia (T-CLL) and T-cell prolymphocytic
      leukemia (T-PLL). Trisomy 3 was observed only in angioimmunoblastic
      lymphadenopathy with dysproteinemia (AILD)-type PTL, T-zone lymphoma, and
      lymphoepithelioid lymphoma. Moreover, the proportion of normal metaphases in
      these PTL was higher than in the other low-grade PTL (P < .01). On the contrary,
      T-CLL, T-PLL, and cutaneous T-cell lymphomas (CTCL) showed complex clones (P <
      .0001), duplications in 6p (P < .01), deletions in 6q (P < .01), trisomy 8q (P <
      .00001), inv(14) (P < .00001), and monosomy 13 or changes of 13q14 (P < .001)
      more frequently than the other low-grade PTL. Trisomy 5 and + X predominated in
      AILD-type PTL. A cytogenetic feature characteristic of AILD-type PTL and CTCL was
      unrelated clones, which were found in 15% of AILD-type PTL and 17% of CTCL. The
      only chromosome aberration restricted to a certain high-grade PTL was
      t(2;5)(p23;q35) in large-cell anaplastic lymphoma. Deletions in 6q, total or
      partial trisomies of 7q, and monosomy 13 or changes of 13q14 turned out to be
      significantly more frequent in high-grade than in low-grade lymphomas (P < .01, P
      < .01, and P < .05, respectively). In summary, the cytogenetic findings in our
      series of 104 PTL enabled us to distinguish not only between low-grade and high
      grade lymphomas but also between various entities of PTL. Thus, the cytogenetic
      findings paralleled the histopathologic diagnoses made according to the updated
      Kiel classification.

PMID- 8286749
TI  - Autosomal recessive chronic granulomatous disease with absence of the 67-kD
      cytosolic NADPH oxidase component: identification of mutation and detection of
      carriers.
AB  - Chronic granulomatous disease (CGD) is characterized by the failure of phagocytic
      leukocytes to kill certain bacteria and fungi. This is caused by deficiencies in
      one of the components of NADPH oxidase, the enzyme in phagocytic leukocytes that
      generates superoxide. In a rare, autosomal recessive form of CGD, a 67-kD
      cytosolic component of NADPH oxidase (p67-phox) is missing. Until now, mutations
      in the gene coding for this protein have not been identified. We now report on a
      10-year-old girl with lymph node and liver abscesses who was recognized as an
      A67(0) CGD patient by lack of NADPH oxidase activity in her granulocytes, a
      cytosolic defect in a cell-free oxidase system, and lack of immunoreactive
      material with an antiserum against the p67-phox protein. mRNA for this protein
      was present in normal amounts in her monocytes. This p67-phox mRNA was reverse
      transcribed, and the coding region was amplified by polymerase chain reaction in
      six overlapping fragments and was sequenced. The patient appeared to be
      homozygous for a G-233-->A mutation, resulting in a nonconservative amino acid
      change (78Gly-->Glu). This mutation was also found in the genomic DNA of this
      patient but not in that of 38 normal donors. Both parents and a sister proved to
      be carriers of the disease, as deduced from the mutation in only one allele. The
      carrier state was also manifested by intermediate superoxide production by their
      intact granulocytes and in the cell-free system.

PMID- 8286750
TI  - Interferon-gamma upregulates interleukin-8 gene expression in human monocytic
      cells by a posttranscriptional mechanism.
AB  - Interleukin-8 (IL-8) is a neutrophil chemotactic and activating cytokine that is
      produced in response to several stimuli. Because monocytic cells are important
      producers of IL-8, we investigated whether interferon-gamma (IFN-gamma), a potent
      inducer of activation and differentiation of mononuclear phagocytes, affected IL
      8 expression in this cell lineage. We found a low constitutive level of IL-8 mRNA
      expression that was upregulated by IFN-gamma in a dose- and time-dependent manner
      and via a protein-synthesis-dependent process in the human monocytic cell line
      U937. IL-8 protein secretion was also stimulated by IFN-gamma. Nuclear run-on
      experiments showed that the IL-8 gene was transcriptionally active in control
      cells and that IFN-gamma did not enhance the transcriptional activity. The
      increase in IL-8 mRNA by IFN-gamma was concomitant with the stabilization of the
      mRNA and, therefore, controlled primarily at a posttranscriptional level. These
      results represent the first evidence that IFN-gamma upregulates IL-8 gene
      expression in cells of the monocytic lineage, and show the involvement of
      posttranscriptional mechanisms in the induction of IL-8 mRNA.

PMID- 8286751
TI  - Hydroxyurea affects cell morphology, cation transport, and red blood cell
      adhesion in cultured vascular endothelial cells.
AB  - Hydroxyurea (HU) significantly increases fetal hemoglobin (Hb) production and
      concomitantly affects passive erythrocyte K transport and cell volume in patients
      homozygous for Hb S, thus decreasing disease severity. Red blood cells (RBCs)
      with Hb S display a greater adherence to vascular endothelial cells (VECs) than
      do Hb A cells, thus increasing the probability of vaso-occlusive crisis. The
      effect of HU on the structure and function of VECs is still unknown. In the
      present study, HU significantly changed, in a dose-dependent manner, the
      morphology and monovalent cation composition of cultured VECs after incubation in
      normal culture medium for up to 10 days in the absence and presence of 0.3
      (therapeutic dose) and 3.0 (toxic dose) mmol/L HU. Treated cells showed
      significant morphologic changes such as an increase in apparent cell size and the
      formation of multinucleated giant cells. The protein content per dish decreased
      by 50% and 80% at 0.3 and 3.0 mmol/L HU, respectively, accompanied by an increase
      in cell Na (maximum, approximately 200%) and cell K (maximum, approximately 50%)
      contents at about days 4 to 6 and 8 to 10, respectively. In addition, HU
      decreased RBC adherence to VECs in experiments with 51Cr-loaded Hb A or Hb S
      RBCs. The HU-induced changes in VEC morphology, cation composition, and RBC
      adherence may be caused or accompanied by alterations in cell membrane
      permeability, transformation of endothelial cells, or decreased number/density of
      VEC adhesion molecules. Precise mechanisms of the HU effects warrant further
      investigation in light of the reported beneficial effects of HU in the treatment
      of sickle cell anemia.

PMID- 8286752
TI  - Fragility and structure of hemoglobin S fibers and gels and their consequences
      for gelation kinetics and rheology.
AB  - Pathogenesis in sickle cell disease depends on whether red blood cells can pass
      the microvasculature during the delay time before hemoglobin S gelation and cell
      rigidification occur. Here we observe individual hemoglobin S fibers by
      differential interference contrast (DIC) microscopy and show that hemoglobin S
      gels and fibers are fragile and easily broken by mechanical perturbation, and
      that breakage results in vast acceleration of gelation kinetics due to the
      creation of new, growing fiber-ends. Hence, in vivo this may be an important
      factor, in addition to hemoglobin concentration and degree of deoxygenation, that
      governs delay time and pathogenesis. Pathogenesis also depends on gel rheology
      and cell rigidification, which depend on fiber cross-linking. We show different
      mechanisms by which X-shaped, Y-shaped, and "zippering" cross-links form.
      Finally, we estimate the "on" rate constant for fiber growth to be about 200
      mmol/(L.s) and obtain a value for the heterogeneous nucleation rate at 13.5
      mmol/L heme.

PMID- 8286753
TI  - Elimination of the O-linked glycosylation site at Thr 104 results in the
      generation of a soluble human-transferrin receptor.
AB  - The transferrin receptor (TfR) is the plasma membrane protein responsible for the
      binding and internalization of the major iron-transport protein, transferrin. The
      function of the single O-linked oligosaccharide near the transmembrane domain of
      the TfR at amino acid Thr 104 is unknown. To elucidate the effect of the O-linked
      carbohydrate on TfR function, the oligosaccharide was eliminated by replacing Thr
      104 with Asp and the mutated cDNA was expressed in a cell line lacking endogenous
      TfR. Elimination of the oligosaccharide at Thr 104 results in a form of the
      receptor that is susceptible to cleavage. A 78-kD soluble TfR that can bind
      transferrin is released into the growth medium. The intact mutant TfR is not
      grossly altered in its structure and does not differ significantly from the wild
      type human receptor in many respects: (1) It shows the same distribution between
      the plasma membrane and intracellular compartments; (2) the binding constant for
      transferrin is similar to that of the wild-type TfR; and (3) it is not rapidly
      degraded. Protein-sequence analysis of the soluble form indicates that the
      sequence begins at amino acid 101 of the intact receptor. This is the same
      cleavage site reported for a soluble form of normal receptor found in human
      serum. Substitution of Gly, Glu, or Met at position 104 also results in increased
      cleavage of the TfR and suggests that elimination of the O-linked carbohydrate at
      position 104 enhances the susceptibility of TfR to cleavage and may mimic a
      naturally occurring process previously described as being related to
      erythropoiesis.

PMID- 8286754
TI  - Hematopoietic recovery after 10-Gy acute total body radiation.
AB  - Considerable data suggest that very high doses of acute total body radiation
      destroy most hematopoietic stem cells and that recovery is possible only after a
      bone marrow transplant. We review data from a radiation accident victim exposed
      to about 10-Gy or more acute total body radiation. Total dose and uniformity of
      distribution were confirmed by physical measurements (paramagnetic resonance),
      computer simulation, and biologic dosimetry (granulocyte kinetics and cytogenetic
      abnormalities). Treatment consisted of supportive measures, transfusions, and
      hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor
      and interleukin-3). Hematopoietic recovery occurred slowly. Granulocytes were
      detectable throughout the postexposure period, exceeding 0.5 x 10(9)/L by day 37.
      There was slower and incomplete recovery of red blood cells and platelets.
      Increases in blood cell production were paralleled by morphologic changes in bone
      marrow biopsies. Gastrointestinal toxicity was moderate. Death from a probable
      radiation pneumonitis infection occurred on day 130. These data indicate the
      possibility of hematopoietic recovery after approximately 10 Gy or more acute
      total body radiation without a transplant. They also suggest that lung rather
      than gastrointestinal toxicity may be dose-limiting under these circumstances.

PMID- 8286755
TI  - Rapamycin, a potent inhibitor of T-cell function, prevents graft rejection in
      murine recipients of allogeneic T-cell-depleted donor marrow.
AB  - We investigated the ability of the macrolide antifungal agent rapamycin (RAPA) to
      inhibit the rejection of T-cell-depleted (TCD) donor bone marrow (BM)
      transplanted into major histocompatibility complex (MHC)-disparate irradiated
      recipients. RAPA (1.5 mg/kg) was administered for 14 days beginning on the day of
      transplant. In the present study, we have tested RAPA administration in two types
      of fully allogeneic BM transplantation (BMT) systems in which host T cells
      mediate the rejection of TCD BM grafts (DBA/1 transplanted into C57BL/6 and
      BALB/c transplanted into C57BL/6). In both instances, RAPA administration
      prevented the rejection of the donor graft, accelerated post-BMT hematopoietic
      recovery, and did not compromise recipient survival. Sequential post-BMT
      fluorescence-activated cell sorter analysis of the spleen showed that RAPA
      administration inhibited host CD4+ and CD8+ T-cell expansion that leads to graft
      rejection. To further investigate the effect of RAPA on T-cell subpopulations, we
      used two congenic donor mouse stains with isolated MHC class I (bm1) or class II
      (bm12) mutations. In these studies, we showed that RAPA administration can
      inhibit MHC class I-restricted CD8+ or class II-restricted CD4+ T-cell-mediated
      graft rejection without compromising recipient survival. The RAPA-facilitated
      alloengraftment is multilineage and durable. We have also shown that RAPA speeds
      hematopoietic recovery post-BMT. We conclude that RAPA represents a new
      therapeutic modality for promoting alloengraftment and accelerating hematopoietic
      recovery.

PMID- 8286756
TI  - Sustained response after recombinant interleukin-3 in diamond blackfan anemia.

PMID- 8286757
TI  - Clonality of chronic neutrophilic leukemia.

PMID- 8286758
TI  - Health care reform: separate and unequal?
AB  - The author discusses the current and evolving forces which are operating to
      prevent the establishment of a universal, comprehensive, equitable, cost
      effective health care system for all Americans. It is the contention of the
      author that managed competition, the most popular of the plans being discussed by
      the Clinton administration, will perpetuate the separate and unequal health care
      system which currently exists. The author supports this conclusion through a
      detailed critique of the proposed managed competition system.

PMID- 8286759
TI  - A comparative analysis of the health beliefs of older black males and females.
AB  - The purpose of this study was to examine differences in the health beliefs of
      older Black males and females. The sample consisted of 66 respondents, 39 females
      and 27 males. The six variables measured in this study were current health
      perceptions, health concerns, resistance-susceptibility perceptions, health
      outlook and rejection of the sick role. The Health Perceptions Questionnaire
      (HPQ) developed by Ware (1976) and a demographic profile were utilized to collect
      data. The HPQ is a self administered instrument, consisting of 32 questions which
      are designed to obtain information relative to an individual's beliefs about
      various aspects of his/her health status. Internal consistency coefficients of
      the HPQ ranged from 0.70 to 0.92. Descriptive statistics were utilized to
      describe the sample. One-way analysis of variance was utilized to test each
      hypothesis. Results revealed rejection of all six hypotheses at p < 0.05 level.

PMID- 8286760
TI  - Using theory to facilitate the transition from faculty to administrator: a
      personal account.
AB  - The author recently made the transition from a faculty role in a large college of
      nursing to the head of the department of nursing at a university in the same
      state. Three theoretical frameworks are discussed in terms of their usefulness to
      the author in determining a framework for decision-making and for understanding
      the new role. Differences in role expectation between faculty and administrator
      are identified and a problem stemming from role-based differences is discussed.
      The author shares some basic beliefs about the responsibilities of leadership.

PMID- 8286761
TI  - Developing a career trajectory: research and community service.
AB  - The faculty of historically black colleges and universities (HBCUs) assume a
      major role in educating the largest share of the country's minority students.
      These institutions have traditionally focused upon teaching and learning
      processes which most result in student successes; conversely, their faculty's
      focus has suffered a decreased emphasis in the areas of research and community
      service. The Project for Faculty and Community Enhancement (FACE) has been
      designed to meet this decreased interest and activity in the areas of research
      and community service. This article will discuss the design and effectiveness of
      Project FACE among nursing faculty at twenty-two HBCUs.

PMID- 8286762
TI  - Administrators and faculty in higher education are aware of the need for the
      promotion of collaborative research and development activities.

PMID- 8286763
TI  - Politics: take an issue and make it yours.

PMID- 8286764
TI  - LPN to ADN/BSN: accelerated curriculum for LPN's.
AB  - This article describes a special project involving the design, implementation and
      evaluation of a flexible education track for licensed practical nurses (LPN)
      within an established nursing program containing an associate degree in nursing
      (ADN) track and a baccalaureate degree in nursing (BSN) track. The LPN track
      facilitated the achievement of the associate degree or baccalaureate degree
      through curricular options which decreased the length of time and/or credit load
      for the LPN. A mechanism also was designed and implemented whereby credit for
      previous nursing knowledge and skills was awarded. Years 1 through 3 of the
      project focused on the advanced placement of LPNs into the associate degree
      program, and years 4 and 5 are an expansion to include the advanced placement of
      LPNs into the baccalaureate degree program.

PMID- 8286765
TI  - Child abuse and neglect: researching the use of a programmed instructional
      manual.
AB  - The problem studied was whether different instructional methods could increase
      assessment skills and affect reporting patterns of child abuse and neglect among
      undergraduate students majoring in nursing. Two hundred nineteen nursing students
      were selected from two urban universities. A programmed instruction manual, Child
      Abuse and Neglect, a pretest booklet, and a posttest booklet were developed
      specifically for this research. The nonequivalent control-group design was
      selected for this quasi-experimental study. Programmed instruction was found to
      be a viable alternative method of instruction on the topic of child abuse and
      neglect. Further, students who are instructed using the programmed instruction
      manual are able to acquire and retain information on the topic equally as well as
      students who are instructed by the more traditional method of lecture and
      discussion.

PMID- 8286766
TI  - Early postnatal assessment of the newborn in the developing country: Malawi.
AB  - The high rate of infant mortality, defined as the number of deaths in the first
      year of life for every 1000 babies born alive (WHO, 1981), is recognized as an
      extremely serious problem in the developing world. Worldwide decreases in the
      number of infant deaths are occurring; however, the gap continues to increase in
      countries with high socioeconomic baselines and those with low per capita income.
      This article discusses ways in which relevant health care policies and the use of
      newborn assessment tools can decrease infant mortality in Malawi Central Africa.
      The description of the tool, Newborn History and Physical Examination Form, for
      assessing the newborn and documenting care from birth until discharge in this
      setting, is included. Post delivery care and the components of a history and
      physical examination are amplified.

PMID- 8286767
TI  - Student success begins with the course guide.
AB  - Nursing faculty have seen enrollments increase over the past few years. Many of
      these students are from non-traditional applicant pools: minority groups, re
      entry students, second career starters, males, and culturally diverse
      individuals. Greater numbers of nurses and nursing students from a broader
      population base represent a very positive trend for the nursing profession as a
      whole. This new trend can be credited as a result of extensive efforts beginning
      in the 1980's to ease the nursing shortage in the United States. Yet teaching
      students with such a wide variety of backgrounds can be quite a challenge for
      faculty. Many students have special learning needs that are addressed poorly in
      the traditional academic setting, but funding cuts and faculty shortages have
      limited opportunities for universities to provide special programs. Faculty must
      become more creative in their efforts to meet students' needs with fewer
      resources. One teaching/learning tool that is literally within the grasp of every
      course instructor, but is highly underrated and inefficiently prepared or used,
      is the course syllabus or guide. Adult learners of all populations benefit from a
      well organized course guide, and it remains one of the most basic and cost
      effective instructional aids that any teacher can supply for a student.

PMID- 8286768
TI  - The Nurse Entrance Test (NET): an early predictor of academic success.
AB  - The purpose of this study is to determine whether a relationship exists between
      beginning nursing students' Nurse Entrance Test (NET) scores and their academic
      success within the first year of professional study. The major goal is to
      identify predictors of academic success so that supportive academic strategies
      could be implemented for the at-risk student. A statistically significant
      relationship is found between NET reading comprehension, math and composite
      scores and nursing grades during the first semester. Test-taking skills, social
      stressors and learning styles were also significantly related to course
      performance. Successful students had significantly higher reading, math, and
      composite scores and lower family and social stress scores than unsuccessful
      students. NET scores were also predictive of nursing grades, accounting for 10
      33% of the variance when entered into a multiple regression equation.

PMID- 8286769
TI  - Lifestyle and morbidity among blacks.
AB  - This descriptive study used the questionnaire method to investigate health
      lifestyle patterns of two Southern Black religious denominations. Baptists and
      Seventh-day Adventists (SDAs). The entire sample numbered 105 persons from urban
      centers. Responses of Baptists (N = 46) were compared with responses of Seventh
      day Adventists (N = 59) on the seven health promoting practices identified in the
      studies of Belloc and Breslow (1972): hours of sleep, appropriate body weight,
      regularity of exercise, moderate alcohol consumption, smoking abstinence,
      regularity of breakfast and moderation of between meal snacks. This was the first
      research focusing on these health behaviors in a Black population in the South.
      Findings showed the groups to be significantly different only in smoking
      behavior, SDAs were more often nonsmokers. The salient implications for practice
      in this study are in the health education area for the individual, the family,
      the community and ethnic groups. This investigator submits that the church as a
      wider support system needs to be utilized by practitioners as a vehicle for
      client education. Several suggestions for further research are presented.

PMID- 8286770
TI  - Health policy reform initiatives to improve the health of black Americans.
AB  - Black Americans comprise 12.4 percent of the United States (U.S.) population and
      is one of the fastest growing minority groups (U.S. Bureau of the Census, 1992).
      Recent health statistics indicate, however, that the life expectancy for Black
      Americans has lagged dramatically behind other minorities and White Americans
      throughout the century (DHHS, 1990). Economic, legislative and social factors
      hinder access to care and the provision of services within the current structure
      of health care in the U.S. Under health care reform, these three factors must be
      redefined to promote access to comprehensive health care services for Black
      Americans. Nursing is being challenged to provide the vision and leadership that
      will influence the key players to support a reform in health policy.

PMID- 8286771
TI  - Research notes: health care reform: implications for nursing research.

PMID- 8286772
TI  - Is anybody listening?

PMID- 8286773
TI  - Black is a color, not a culture: implications for health care.

PMID- 8286774
TI  - Home parenteral nutrition for the management of chronic intestinal failure: a 34
      patient-year experience.
AB  - Home parenteral nutrition (HPN) was used for the treatment of 18 patients with
      chronic intestinal failure (CIF): short bowel syndrome (9), extensive intestinal
      disease (4), motility disorder (4), entero-enteric fistulas (1). The underlying
      diseases were: chronic inflammatory (7), mesenteric vascular (4), scleroderma
      (2), pseudo-obstruction (2), malignancy (2), radiation enteritis (1). HPN was
      more effective on protein-calorie nutritional status than on fluid and
      electrolyte balances. About two-thirds of the patients achieved full or partial
      social rehabilitation. During the 6 months before HPN, there were 20
      hospitalizations (mean stay: 55 days). During HPN (mean length of treatment: 22
      months/patient) there were 16 hospitalizations (mean stay: 22 days), 8 of which
      were caused by HPN complications (sepsis and deep vein thrombosis; overall
      incidence of catheter-related complications: 0.411 per patient-year). Bone
      demineralization, liver abnormalities and biliary stones developed, respectively,
      in 57%, 28% and 11% of the cases. The underlying intestinal condition played a
      role in their pathogenesis. The annual cost of HPN ranged from 40 (Hospital
      Pharmacy Service) to 80 (commercial firm) million lire per patient. To sum up,
      HPN improves the nutritional status and the quality of life of patients with CIF,
      and the risk of complications is acceptable. The medical and social advantages
      are considered to offset the cost of the technique.

PMID- 8286775
TI  - Helicobacter pylori infection, cigarette smoking and alcohol consumption. A
      histological and clinical study on 286 subjects.
AB  - Helicobacter pylori (Hp) is connected with active/chronic gastritis, gastric
      gastric and duodenal ulcer. It is not known whether exogenous factors are
      involved in Hp infection. The aim of this prospective study, performed on 286
      consecutive subjects undergoing upper gastrointestinal endoscopy, was to evaluate
      the influence of smoking and alcohol consumption on Hp infection. For each
      patient the following parameters were taken into account: sex, age, smoking (no,
      < 10, > 10 cig/day) and alcohol (no, < 40, > 40 g ethanol/day) intake, antiulcer
      therapy (no, H2-blockers, omeprazole, sucralfate), presence of gastric or
      duodenal ulcer (DU). At least two biopsies from both the antrum and the corpus
      were obtained for histological examination; the gastritis was classified and
      scored according to the Sydney system. STATISTICS: chi-squared test (corrected),
      Fisher's exact test. RESULTS: 43 pts had Hp (27M, 16F; age 57.8 yrs, range 23
      91), 47 Hp ++ (25M, 22F; age 61.1, range 19-86), 81 Hp + (48H, 33F; age 56, range
      16-84), 115 Hp- (75M, 40F; age 57.8, range 19-84). Hp infection was found to be
      significantly correlated with presence of ulcer symptoms, gastritis, lymphoid
      follicles and, among DU patients, with active DU. The other parameters considered
      did not influence Hp infection. In conclusion smoking habits and alcohol
      consumption do not affect Hp infection of the stomach.

PMID- 8286776
TI  - Long-term effects in bilio-digestive shunts.
AB  - Duodenogastric reflux (DGR) and its effects were studied in patients with bile
      stones, operated by various bilio-digestive by-pass techniques, and followed up
      for 13-73 months. Ten patients underwent cholecystectomy and
      choledochoduodenostomy (CD), eight cholecystectomy and transduodenal
      sphincteroplasty (TDS) and ten cholecystectomy and endoscopic papillotomy (EP).
      The control group consisted of eight patients who had undergone minor surgery.
      DGR was studied by 99mTc-DISIDA scanning, and primary and secondary bile acids
      were assayed in reflux fluid. The effects were studied by gastroduodenoscopy and
      biopsies from the body of the stomach and antrum. Only patients operated by TDS
      (7/8) presented significant increases in DGR and bile acids (p < 0.008). Half the
      patients in this same group (4/8) had chronic atrophic gastritis and major
      clinical disorders. Some physiopathological mechanisms possibly involved in DGR
      and its effects are suggested.

PMID- 8286777
TI  - Serum malondialdehyde and mitochondrial aspartate aminotransferase activity as
      markers of chronic alcohol intake and alcoholic liver disease.
AB  - Since lipid peroxidation is a well-know mechanism of alcohol-related liver
      damage, the aim of the present study was to assess the role of serum
      malondialdehyde (MDA), a secondary product of lipoperoxidation, in the detection
      of alcoholism and different stages of alcoholic liver disease and to correlate
      serum levels of malondialdehyde with other markers. Sixty-five patients with a
      mean alcohol intake of 151 gr/day, were divided into three groups: alcoholics
      with normal liver function (ANLF, 7 pts), non-cirrhotic alcoholic liver disease
      (NCALD, 26 pts) and alcoholic cirrhosis (ALC, 32 pts). The control group
      consisted of 15 healthy subjects. Serum MDA was measured by the thiobarbituric
      acid reaction test, and mitochondrial aspartate aminotransferase (mAST) with
      immunochemical assay. MDA had a higher sensitivity (70% vs 37.5%) and specificity
      (100% vs 93%) than mAST in detecting alcohol abuse, irrespective of the presence
      of liver disease. Serum MDA levels were significantly higher in all three groups
      than in controls (2.3 +/- 0.1 nmol/ml), the highest value being found in NCALD
      (4.6 +/- 0.4). Serum MDA levels were correlated with prothrombin time (p < 0.005)
      and blood alcohol levels (p < 0.05). mAST serum activity was also significantly
      higher in all three groups than in controls. A significant correlation was found
      between serum MDA and mAST only when the whole group was considered.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8286778
TI  - Does alcohol activate mast cells in peptic ulcer?

PMID- 8286780
TI  - Specialist training in gastroenterology in the European Economic Community: the
      case for European boards.

PMID- 8286779
TI  - Primary systemic amyloidosis with giant hepatomegaly and portal hypertension: a
      case report and a review of the literature.
AB  - Amyloidosis is a manifestation of a group of diseases resulting from the variable
      infiltration of multiple organs by a fibrillar protein called amyloid. Hepatic
      involvement in amyloidosis is common both in the primary and in the secondary
      forms, whereas clinically-dominant liver amyloidosis is relatively rare. The
      authors describe a case of primary systemic amyloidosis with giant hepatomegaly,
      portal hypertension and renal insufficiency; the patient did not develop
      jaundice, ascites or gastrointestinal bleeding but died 6 months later, death
      being due to cerebral haemorrhage.

PMID- 8286781
TI  - Immunohistochemistry of a human type I pneumocyte-associated protein in lung.
AB  - A mouse monoclonal antibody to a human lung lavage protein was raised using
      proteins, with the potential ability to bind surfactant, as the immunogen. The
      proteins were isolated from cadaver lung lavage. The antibody was tested for its
      reactivity with lung and other organs. It reacted with type I pneumocytes and
      some of the nonciliated cells in the surface epithelium of distal bronchioles.
      Staining was also seen in the cells surrounding the glandular structures,
      superficial keratinocytes of the skin, endothelium, and nerve sheath cells. With
      the exception of bronchiolar cells, the stained cells have a squamous morphology,
      and this protein may serve as a marker or determinant of this characteristic of
      cells. In pathologic lungs some of the cells in air spaces with
      "bronchiolarization" of the epithelium exhibited staining for the protein. It
      could not be ascertained whether the stained cuboidal cells were reactive type II
      pneumocytes or distal bronchiolar cells. The intraalveolar material in pulmonary
      alveolar proteinosis did not show remarkable staining for the protein. Even
      though the protein is not unique to type I pneumocytes, it may serve as a marker
      for these cells in the study of their development and biology.

PMID- 8286782
TI  - Biosynthetic routing of pulmonary surfactant proteins in alveolar type II cells.
AB  - Surfactant proteins A, B, and C (SP-A, SP-B, and SP-C) are synthesized in
      alveolar type II cells. SP-B and SP-C are both synthesized as large precursor
      molecules that are proteolytically processed to their mature sizes. In a previous
      immunoelectron microscopic study, we showed that precursor SP-B is processed to
      its mature size in multivesicular bodies. In the present study, using a specific
      antibody against precursor SP-C, we demonstrate that precursor SP-C is present in
      the same intracellular compartments of the biosynthetic pathway, i.e.,
      endoplasmic reticulum, Golgi complex, and multivesicular bodies, as precursor SP
      B. Since mature SP-C is known to be present in multilamellar bodies, this
      suggests a biosynthetic routing and site of processing of this protein similar to
      those of SP-B. Double-labeling experiments using antibodies against SP-A,
      precursor SP-B, precursor SP-C, and an antibody against HA I, an adaptor protein
      involved in the budding of transport vesicles from the Golgi complex, showed that
      the different surfactant proteins traverse and exit the Golgi complex via the
      same route. The surfactant proteins do not exit the Golgi complex via HA I
      positive coated buds or vesicles. These data are in accordance with the concept
      that SP-A, SP-B, and SP-C are transported together through the same biosynthetic
      pathway via multivesicular bodies to multilamellar bodies.

PMID- 8286783
TI  - Interaction of lung surfactant protein A with alveolar macrophages.
AB  - We analyzed the binding mechanism of human recombinant lung surfactant protein A
      (SP-A) to rat alveolar macrophages using anti-SP-A antiserum and protein A coated
      onto gold particles. Results were compared with our recent data on binding and
      uptake of SP-A-coated colloidal gold particles. The rationale for the current
      approach was to avoid any possible steric effects on SP-A binding to the cell
      surface. Binding of unlabeled SP-A depends on the presence of calcium ions in the
      medium and involves a mannose-specific mechanism. Binding is partly inhibited by
      the collagenase-resistant fragment of SP-A, representing mainly the globular part
      of SP-A. Taken together, these facts indicate binding of SP-A via the
      carbohydrate binding site on the globular region of SP-A. On the other hand, a
      partial inhibition of SP-A binding by fragments of C1q (representing the
      collagenous region of C1q) indicates a second binding site for SP-A by the
      collagen-like portion to the C1q receptor of macrophages. We conclude that two
      different mechanisms are probably involved in SP-A binding to alveolar
      macrophages. Specificity of the binding was shown with fluorescein-labeled SP-A.
      Binding was inhibited by an excess of unlabeled SP-A. Binding and uptake of SP-A
      are seen only with alveolar macrophages and not with other macrophage populations
      isolated from rat, such as liver macrophages (Kupffer cells), resident peritoneal
      macrophages, and peritoneal macrophages activated by Corynebacterium parvum.
      Therefore, binding sites for SP-A occur exclusively on alveolar
      macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286784
TI  - Ontogeny of platelet-derived growth factor receptor in fetal rat lung.
AB  - There is increasing evidence that platelet-derived growth factor (PDGF) or PDGF
      like molecules play a role in fetal lung morphogenesis. Our previous studies
      demonstrated the presence of PDGF-AA and PDGF-BB homodimers in fetal rat lung. To
      study further the target cells of PDGF in lung development, immunolocalization
      studies of PDGF receptors (PDGFR) were conducted on embryonic and fetal rat lung
      from day 13 to day 21 of gestation (term = 22 days) using two polyclonal PDGFR
      antibodies, one of which one recognizes both alpha and beta receptors (PDGFR
      alpha/beta), while the other is specific for the beta receptor (PDGFR-beta). A
      similar immunostaining pattern for both antibodies was noted. Immunoreactivity to
      PDGFR was evident in both epithelial and mesenchymal cells of the embryonic lung
      bud as early as 13 days gestation. The number of PDGFR immunoreactive cells
      increased with advancing gestation. Intense immunoreactivity was noted in both
      epithelial cells and interstitial cells during the saccular stage of lung
      development. The immunoreactivity to PDGFR was localized to the apical/luminal
      side of bronchial and distal airway epithelial cells. PDGFR-immunopositive
      bronchial and vascular smooth muscle cells were detected only during the
      canalicular and saccular stages of lung development. Immunopositive endothelial
      cells lining the internal vascular plexuses were observed from days 14-16 of
      gestation. No PDGFR was detected in endothelial cells of large pulmonary vessels.
      We conclude that PDGFR are present in airway epithelial cells, interstitial
      cells, and bronchial and vascular smooth muscle cells and that gestation
      dependent up- and down-regulation of PDGFR may play a role in developmental
      regulation of PDGF bioactivity during lung morphogenesis.

PMID- 8286785
TI  - Ultrastructural features of alveolar epithelial cells in the late fetal pulmonary
      acinus: a comparison between normal and hypoplastic lungs using a rat model of
      pulmonary hypoplasia and congenital diaphragmatic hernia.
AB  - The aim of this study was to describe and compare the ultrastructural features
      and functional maturity of alveolar epithelial cells in hypoplastic and normal
      fetal rat lungs. Pulmonary hypoplasia in association with congenital
      diaphragmatic hernia was induced in fetuses by administration of 2,4
      dichlorophenyl-p-nitrophenylether (Nitrofen) to pregnant Sprague Dawley rats (100
      mg on day 10 of gestation). Lung tissue of Nitrofen-exposed and control fetal
      rats aged 19-22 days (vaginal plug day 1, birth day 23) was embedded in Epon.
      Semithin (1 micron) toluidine blue-stained sections were examined by light
      microscopy; ultrathin sections (approximately 80 nm) were studied via
      transmission electron microscopy. In bronchoalveolar lavage fluid from control
      and Nitrofen-exposed fetuses (day 22), phospholipid fractions and surfactant
      protein A content were measured semiquantitatively. On day 19 both control and
      Nitrofen-exposed lungs contained only cuboid alveolar epithelial cells; from day
      20 there were cuboid, low cuboid, and thinner epithelial cells. The (low) cuboid
      cells contained large glycogen fields, some precursory stages of multilamellar
      bodies (MLBs), and just a few mature MLBs on day 19 and 20; smaller glycogen
      fields, more precursory stages, and more mature MLBs on day 21; and little or no
      glycogen but many precursory stages and mature MLBs on day 22. The thinner cells
      contained little or no glycogen and a few precursory stages of MLBs on days 20
      22; very thin cells on day 22 contained neither glycogen nor any precursory
      stages of MLBs. MLBs and tubular myelin were seen in the lumens of future air
      spaces from day 20 onward. Nitrofen-exposed lungs differed from control lungs in
      that inclusion bodies (IBs) were less numerous in (low) cuboid alveolar cells on
      days 19 and 20, and more glycogen was seen on day 22. In addition intra- and
      extracellular "MLBs" in exposed lungs more often had an unusual appearance, i.e.,
      a confluent structure and higher electron density. However, despite morphologic
      differences, there was no clear difference in phospholipid composition and SP-A
      content per mol phospholipid in bronchoalveolar lavage fluid. We conclude that
      morphologically hypoplastic lungs are less mature near term, without an apparent
      effect on surfactant composition.

PMID- 8286786
TI  - Clara cell differentiation in the mouse: ultrastructural morphology and
      cytochemistry for surfactant protein A and Clara cell 10 kD protein.
AB  - The morphologic and functional differentiation of the nonciliated columnar
      (Clara) cell, one of two secretory cell types in distalmost bronchioles in
      mammals, was studied in the mouse. Lungs from embryos (16-19 days of
      developmental age, dDA; birth on day 19), postnatal animals (5-20 days
      postnatally dPN), and adult animals were investigated by transmission electron
      microscopy, using standard staining procedures and immunogold (GAR-Au10) labeling
      for SP-A and Clara cell 10 kD antigen (CCA). At 16 dDa, all the columnar
      epithelial cells lining prospective distalmost bronchioles lacked distinctive
      features. By 17 dDa, some cells displayed a few cilia or apical dense granules.
      At 18 dDa, many nonciliated columnar cells had apical protrusions, as are seen in
      adult Clara cells. Apical concentrations of glycogen observed in nonciliated
      columnar cells perinatally were absent by 5 dPN, whereas apical dense granules
      became more abundant. Profiles of smooth and rough endoplasmic reticulum (ER),
      which had been randomly distributed, exhibited a selective, adult distribution at
      20 dPN (apical vs. basal cytoplasmic domains). Labeling for SP-A and CCA, which
      was almost absent between 17 and 19 dDa, reached adult levels at the same time.
      The two proteins differed in distribution. SP-A predominated in adluminal
      cytoplasmic areas, where it was found over dense granules, vesicles, and
      multivesicular bodies; it was also present in bronchiolar lumens and
      intercellular spaces but not in rough ER or Golgi apparatus. In contrast, CCA
      showed a more uniform distribution; it was present over the same structures as SP
      A and in the synthetic organelles. Ciliated columnar cells were virtually devoid
      of SP-A and CCA. We conclude that mouse Clara cells acquire a mature phenotype by
      20 dPN. They are likely to be involved in recycling and/or degradation of SP-A
      that is internalized from airway lumens through their apical or lateral cell
      borders; furthermore, they synthesize the Clara cell 10 kD protein. These two
      Clara cell functions (first detectable late prenatally) reach mature levels by 20
      dPN.

PMID- 8286787
TI  - Role of alveolar macrophage chemotaxis and phagocytosis in pulmonary clearance
      responses to inhaled particles: comparisons among rodent species.
AB  - Alveolar macrophages (AM) play an important role in clearing inhaled particles
      from the lung. The mechanisms through which macrophages identify particles that
      have been deposited in the alveolar regions is not well understood, although
      macrophage motility and phagocytic functions appear to be prerequisites for
      efficient clearance of inhaled materials. In previous studies, we assessed the
      mechanisms of macrophage-mediated clearance of inhaled particles using a rat
      model. In this regard, it appears that one mechanism by which rat alveolar
      macrophages are recruited to sites of particle or fiber deposition is through
      complement activation and consequent generation of chemotactic factors by the
      inhaled particulates. Whether this mechanism is operative in other rodent species
      remains an unanswered question. The current studies were undertaken to compare
      pulmonary clearance responses in several rodent species exposed to carbonyl iron
      (CI) particles. In vitro and in vivo pulmonary clearance responses were evaluated
      using one strain each of mouse, hamster, rat, and guinea pig. In vitro studies
      showed that hamster AM had the greatest phagocytic activity and that rat AM
      migrated best to complement-dependent chemotactic factors. Subsequently, groups
      of animals from each species were exposed to CI particles for 1 or 6 hr at
      aerosol concentrations of 100 mg/m3. Particle depositions patterns in the distal
      lung were nearly identical for all species, although enhanced numbers of CI
      particles were deposited on alveolar duct bifurcations of either rats or mice
      compared to hamsters, and particle deposition in guinea pigs was substantially
      lower. Time course studies showed that enhanced numbers of rat AM migrated to
      deposition sites and phagocytized particles, and this correlated with increased
      numbers and percentages of phagocytic macrophages recovered by lavage (P < 0.01).
      In vivo phagocytic rates were the lowest in the mouse, and this correlated with
      reduced phagocytic rates in vitro. It is concluded from these studies that the
      rat may be the most efficient rodent species in clearing inhaled iron particles.
      In addition, it is conceivable that hamster AM are recruited to sites of particle
      deposition by a noncomplement-mediated mechanism.

PMID- 8286788
TI  - Surfactant and inhaled particles in the conducting airways: structural,
      stereological, and biophysical aspects.
AB  - We have investigated the displacement into the sol phase of inhaled particles
      deposited in the intrapulmonary conducting airways. Hamsters inhaled an aerosol
      of monodisperse polystyrene particles of 6 microns diameter. Their lungs were
      fixed by intravascular perfusion, and light and electron microscopy was used to
      study the epithelial coating. The surfactant film at the wall-air interface was
      investigated by measuring its surface tension. The number of particles retained
      was determined stereologically. In addition we investigated the displacement of
      spherical particles in vitro on a DPPC monolayer in a Langmuir-Wilhelmy surface
      balance and determined the surface tension in vivo in the horse trachea by video
      bronchoscopy, applying the droplet spreading method. We found that particles
      deposited onto a surfactant film were pulled into the aqueous subphase, and we
      concluded that surface forces due to the airway surfactant likely displace
      deposited particles into the periciliary fluid (sol phase). Comparing lungs fixed
      immediately after inhalation with lungs fixed 24 hr after inhalation revealed
      that 86% of the particles retained in the intrapulmonary conducting airways
      immediately after inhalation had been cleared within 24 hr. One-third of the
      particles of the lungs fixed immediately after inhalation was phagocytized. The
      combination of structural and stereological analyses with in vitro and in vivo
      measurements has led to new insights into the role of airway surfactant with
      respect to the fate of inhaled particles, which may have important consequences
      regarding the effects of hazardous particles. These studies may also help to
      evaluate the deposition pattern and clearance of therapeutic particles, with
      important implications for their therapeutic use.

PMID- 8286789
TI  - Aerosolized fluorescent microspheres detected in the lung using confocal scanning
      laser microscopy.
AB  - Aerosolized fluorescent microspheres were used to study particle deposition in
      site-specific regions of the lung with confocal laser scanning microscopy. A
      nebulizer was used to aerosolize microspheres followed by passage through a
      heated discharging column to reduce static charge and to remove water surrounding
      each microsphere. Precoating of microspheres with albumin helped to minimize
      displacement during vascular fixation of the lungs. Confocal laser microscopy
      facilitated visualization of microspheres throughout the bronchial tree, ducts,
      and alveoli of the lungs. The use of fluorescent microspheres and confocal laser
      imaging provided distinct advantages compared with other methods to study lung
      particle deposition due to (1) the generation of single microspheres of uniform
      size by nebulization, (2) easy detection of microspheres in large slabs of
      microdissected lung tissues, (3) excellent resolution of tissue surfaces and
      microspheres for an infinite number of orientations and planes of section, and
      (4) the ability to visualize microspheres below fluid lining layers and on
      surfaces that could not easily be done by other methods of microscopy.

PMID- 8286790
TI  - Acute lung injury during bacterial or fungal sepsis.
AB  - We compared physiological and ultrastructural indices of acute lung injury (ALI)
      during septic shock caused by taxonomically diverse pathogens to distinguish ALI
      due to endogenous inflammatory mediators vs. microbial exotoxins or other
      factors. Conscious rats were infected i.v. with gram-negative Escherichia coli
      (EC, serotype 055:B5), exotoxin-C producing gram-positive Staphylococcus aureus
      (SA), or yeast-phase Candida albicans (CA, a clinical isolate). Viable inocula of
      10(10) EC, 10(10) SA, or 10(9) CA caused lethal shock in < 24 h, but distinct
      types of ALI were noted after bacteria vs. fungi. Within 0.5 h of EC infection,
      leukocytes marginated in the lung vasculature; by death at 6-14 h, animals were
      hyperoxemic but not acidemic, and showed slight interstitial edema with increased
      wet/dry weight ratios (W/D = 5.22 +/- 0.10, mean +/- SE, vs. 4.86 +/- 0.07 in
      controls, P < 0.05). Similarly mild ALI occurred after 10(10) SA. In contrast,
      within 0.5 h of CA infection, yeast were visible within lung intravascular
      leukocytes. By death at 6-12 h, CA animals showed hyperoxic acidemia and moderate
      ALI with capillary obstruction, interstitial hemorrhage, and elevated lung W/D
      (5.52 +/- 0.13, P < 0.01 vs. controls) associated with yeast-mycelial
      transformation. Prior neutropenia accelerated mortality and worsened ALI after
      CA, with hypoxemic acidemia, increased lung W/D (7.23 +/- 0.34, P < 0.05 vs.
      other groups), capillary occlusion, perivascular and alveolar hemorrhage, and
      septal disruption by mycelia. Bacteremia induced large increases in serum tumor
      necrosis factor-alpha (TNF) and interleukin-1 alpha within 1.5 h, but these
      cytokines remained low in CA animals, even at death. Neither survival nor ALI
      after EC or CA was altered by pentoxifylline, which attentuated TNF production,
      or by cyclooxygenase inhibition with ibuprofen. Thus, overall ALI severity
      correlated with physiological indices of pulmonary function, but ultrastructural
      changes correlated better with pathogen type than circulating cytokine or
      eicosanoid mediators. Whereas lethal bacteremia induced early cytokinemia and
      mild ALI with or without bacterial exotoxins, moderate ALI apparently was
      mediated by fungal exotoxins during lethal candidemia, which worsened during
      neutropenia due to enhanced mycelial proliferation.

PMID- 8286791
TI  - In vivo effects of endotoxin on DNA synthesis in rat nasal epithelium.
AB  - Airway inflammation in bacterial infections is characterized by the presence of
      neutrophils and often epithelial injury and repair. Release of endotoxin from
      bacteria may contribute to these processes. The purpose of this study was to
      determine the in vivo effects of repeated endotoxin exposure on DNA synthesis in
      rat nasal epithelium in the presence and absence of neutrophilic influx. Rats
      were intranasally instilled, once a day for 3 days, with endotoxin or saline
      (controls). Before the first and third instillations, half of the saline and
      endotoxin-instilled animals were depleted of circulating blood neutrophils by
      administering a rabbit anti-rat neutrophil antiserum. Rats were sacrificed 6 or
      24 h after the last instillation. Two hours prior to sacrifice, rats were
      intraperitoneally injected with bromodeoxyuridine (BrdU), an analog of thymidine
      that is incorporated in the nucleus of cells in the S-phase of the cell cycle.
      Nasal tissues were processed for light microscopy and immunohistochemical
      detection of BrdU in nasal epithelial cells. The numbers of nasal epithelial
      cells, BrdU-labeled epithelial nuclei, and neutrophils per millimeter of basal
      lamina in the epithelium lining the nasal turbinates in the proximal nasal
      passages were determined by morphometric analysis. We did not observe a
      neutrophilic influx in the nasal tissues of neutrophil-depleted rats at 6 or 24 h
      after the last endotoxin instillation; however, the numbers of nasal epithelial
      cells and the BrdU-labeling index were significantly increased compared to saline
      instilled controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286793
TI  - The epipharynx in normo- and pathogenesis.
AB  - We studied the development of the epipharynx in normal human ontogeny comparing
      findings in fetuses with severe CNS malformations with those of normal fetuses of
      a comparable stage of development. Normally, the epipharynx forms a tube and
      bends at a right angle, whereas, in the fetuses with CNS malformations, the
      epipharynx develops as a balloon-like form of slightly triangular shape. In
      hydrocephaly, it formed a narrow tube that was nearly vertical. We concluded that
      the early formation of the epipharynx is influenced by the separation of the
      notochord and the formation of the basicranium, by ascendant processes during
      vertebrogenesis, and by the neotenic development of the maxillomandibular
      complex.

PMID- 8286792
TI  - A step section method for full histopathological assessment of carcinogen
      affected target tissue during respiratory carcinogenesis.
AB  - Studies of carcinogenesis that are not limited to overt neoplasms but also
      involve evaluations of preneoplastic stages require histopathological assessment
      of the entire carcinogen-affected tissue so that the true nature and sequence of
      the progressive process can be determined. The customary serial sectioning
      approach achieves this goal, but at an inordinate logistic cost. In studies of
      hamster bronchial carcinogenesis, a step section method was compared to a quasi
      random approach and to the customary serial section method. The step section
      method achieved the same diagnostic completeness as serial sectioning, but at a
      two orders of magnitude reduction in costs.

PMID- 8286794
TI  - The differentiation and involution of the mullerian duct in the rat.
AB  - The structural differentiation of the Mullerian ducts of both sexes was studied
      in rat fetuses from 15 to 21 days of gestation. Differences between the male and
      female Mullerian ducts were observed from the 17th day onward. The epithelium of
      male Mullerian duct lost its regular arrangement, the increased lysosomal
      activity and disintegration of some cells was found. The involution of the male
      duct was accompanied by the condensation of the surrounding mesenchyme with the
      participation of macrophages. The female Mullerian duct was lined with simple
      columnar epithelium; its pattern remained indifferent until birth. The apical
      migration of centrioles and solitary cilia formation belonged to the typical
      findings from the 18th day. Neither ciliated cells nor multiple centriole
      replication were observed in oviductal segment of Mullerian duct.

PMID- 8286795
TI  - Histological and submicroscopical findings on the seminiferous parenchyma in rams
      after copper oxide intoxication from industrial emissions.
AB  - In this work the author examined the histological and submicroscopical picture of
      the seminiferous parenchyma in 5 breeding rams from a herd in which intoxication
      with copper oxide from industrial emissions of a copper producing plant had been
      diagnosed. The toxic effect irreversibly damages all developmental stages of the
      germ cells. It injures the cell membranes of both germ cells and Sertoli cells.
      Similar changes were observed on the interstitial cells. The degree of injury to
      the germinative epithelium confirms its significant role in the decreased
      reproduction rate of the herd under examination.

PMID- 8286796
TI  - Structure and development of the internal male reproductive organs in the
      dragonfly Tramea virginia (Rambur).
AB  - The internal male reproductive organs of Tramea virginia consist of a pair of
      testes, a pair of vasa deferentia (which in adult modify distally into seminal
      vesicles), a median sperm sac and a short ejaculatory duct. The development of
      the genital tract occurs in the ultimate nymph. Each testicular lobule contains
      the gametes showing collectively only a single stage of spermatogenesis. The
      process of spermatogenesis is vigorous in the ultimate nymph and, therefore, the
      newly emerged imago contains active spermatozoa in its testicular lobules.
      Spermatophores are not observed in the genital tract of the adults.

PMID- 8286797
TI  - A scanning electron microscopic study on three-dimensional organization of human
      diaphragmatic lymphatics.
AB  - Three-dimensional organization of diaphragmatic lymphatics in five fetuses was
      studied by the lymphatic casts of scanning electron microscope. A new resin
      consisting of piperylene, acrylic ester and styrene was used instead of Mercox.
      The diaphragmatic lymphatics formed rich networks in the muscular portion. There
      were two layers of lymphatic networks, i.e. the submesothelial network and the
      deeper network and only one layer in the tendinous portion of the diaphragm. The
      lymphatic networks were more dense in the tendinous portion than these in the
      muscular portion. The lymphatics were mainly composed of main lymphatic vessels
      and anastomosing side branches. The side branches often communicated the
      submesothelial network with the deeper network in the muscular portion. The main
      lymphatics were connected at regular intervals by way of transverse side branches
      in the tendinous portion. Numerous constrictions and notches showing the presence
      of lymphatic valves were often found on the cast surface of the main lymphatic
      vessels and the side branches. The lymphatics extended as far as the terminal
      branches, i.e. the lymphatic lacunae recognized as broad, flattened and blind
      ended. In the present study, three-dimensional organization of human
      diaphragmatic lymphatics was for the first time described. It was suggested that
      the passageway of the lymph flow out of the peritoneal cavity may be explained.
      From the peritoneal stomata, the lymph of the peritoneal cavity flowed into the
      channels under the peritoneum, then into the lymphatic lacunae and finally into
      the lymphatic networks under the diaphragmatic pleura.

PMID- 8286798
TI  - Remembrance of Professor MUDr. Vladimir Munka, DrSc. (2. 12. 1922-31. 7. 1986) to
      his unfinished seventies.

PMID- 8286799
TI  - The segmental Bauplan of the rostral zone of the head in vertebrates.
AB  - Observations in a wide selection of lower vertebrate embryos have confirmed
      classical descriptions concerning segmentation of the early head mesoderm. The
      premandibular (PM) segment is seen as the most rostral representative of a
      continuous rostro-caudal series of condensations in the paraxial mesoderm,
      luminisations within which are secondary and variable in occurrence and form. The
      premandibular condensations are typically in continuity across the midline; the
      confluence, which comes to lie behind Rathke's pouch, marks the site of first
      mesoderm formation behind the oral membrane. The underlying consistency of pre
      otic segmental pattern throughout the vertebrates is frequently obscured by
      superimposed variation in morphological detail between species, reflecting the
      dynamic nature of the morphogenetic tissue processes. Luminisation is one such
      morphogenetic epiphenomenon. Variations in it account for the terminal (Platt's)
      vesicle and "proboscis pores": such structures cannot therefore be safely used to
      infer evolutionary homologies. Many previous difficulties facing segmentation
      theory are explained as the result of failure to take account of the dynamic
      nature of the responsible morphogenetic events.

PMID- 8286800
TI  - Principal types of functional architecture of cancellous bone in man.
AB  - The cancellous bone architecture in man is locally specific. Several principal
      types can be distinguished, depending on the kind of loading and movement in the
      joint in one, two or more directions. Under multidirectional load the spongiosa
      trabeculae form spatial fans seen as two crossing systems on plane sections.
      Marked differences exist between the bone structure under concave joint surfaces
      and the convex ones. The analysis testifies the correctness of the author's own
      theory on the development of the cancellous bone architecture. According to this
      theory every trabecular system corresponds to other direction of maximal
      principal stress in the course of movement. Both crossing systems in the
      metaphysis are pressure systems, corresponding to opposite extreme positions in
      the joint. Tension systems can be found in sites of ligament or tendon insertions
      and closely under concave articular surfaces only.

PMID- 8286801
TI  - Effect of multiple staggered doses of calcium on the bioavailability of
      ciprofloxacin.
AB  - OBJECTIVE: To determine the effect on the relative bioavailability (Fr) of a
      staggered single dose of ciprofloxacin given two hours after a morning dose of
      calcium carbonate given three times daily over the three previous days. DESIGN:
      Thirteen male volunteers participated in this randomized, nonblinded, crossover
      investigation; 12 subjects were included in the final analysis. SETTING: Data
      collection and ciprofloxacin administration occurred at Albany Medical Center, a
      tertiary-care teaching institution. Calcium carbonate administration was on an
      outpatient basis. RESULTS: For 12 volunteers, the mean +/- SD Fr of ciprofloxacin
      staggered with calcium was 0.87 +/- 0.23 (noncompartmental model) and 0.98 +/-
      0.27 (compartmental model). Other statistically significant findings were a
      decrease in the time to maximum concentration of ciprofloxacin staggered with
      calcium in serum compared with ciprofloxacin alone (from 1.76 +/- 0.54 to 1.23 +/
      0.52 h in the noncompartmental model; p < 0.05), and a decrease in the same
      parameter (from 1.92 +/- 0.96 to 0.77 +/- 0.53 in the compartmental model; p <
      0.005). Maximum concentration of ciprofloxacin staggered with calcium was
      decreased in the noncompartmental model compared with ciprofloxacin alone (from
      2.11 +/- 0.72 to 1.60 +/- 0.33, respectively; p < 0.05). The elimination half
      life and area under the concentration-time curve of ciprofloxacin were not
      significantly altered. CONCLUSIONS: Repeated doses of calcium carbonate,
      administered two hours before ciprofloxacin, did not significantly alter the Fr
      of this fluoroquinolone.

PMID- 8286802
TI  - Effect of frequently prescribed cardiovascular medications on sexual function: a
      pilot study.
AB  - OBJECTIVE: To determine the effect on male sexual function of initiating any one
      of the cardiovascular medications most frequently prescribed at our institution.
      DESIGN: Men were surveyed via telephone when they received a new prescription for
      hydrochlorothiazide, furosemide, lisinopril, verapamil, nifedipine, or diltiazem,
      and after 30 days of daily medication ingestion. To assess Hawthorne effect, men
      who had no change to their medication regimen also were surveyed at the time of
      medication refill for maintenance therapy and 30 days later. PARTICIPANTS:
      Community-dwelling male veterans who received a single new prescription between
      January 1 and April 1, 1992 (n = 134). MAIN OUTCOME MEASURES: Responses to
      questions about sexual interest, erectile function, orgasmic ability, and sexual
      satisfaction. RESULTS: Men who had no change to their medication regimen showed
      no change in sexual interest, erectile function, orgasmic ability, or
      satisfaction. Hydrochlorothiazide was associated with decreased orgasmic ability
      (p = 0.008). Although none of the other changes were statistically significant (p
      < 0.05), both nifedipine and diltiazem showed a trend toward improved sexual
      function. CONCLUSIONS: Hydrochlorothiazide may be associated with anorgasmia.
      More study is needed to determine if nifedipine and diltiazem improve erectile
      function. Furosemide, lisinopril, and verapamil likely have no effect on sexual
      function.

PMID- 8286804
TI  - Rhodococcus equi pneumonia: case report and literature review.
AB  - OBJECTIVE: To present a case of Rhodococcus equi (RE) pneumonia and discuss its
      pathophysiology and treatment. CASE SUMMARY: An HIV-positive patient presented
      with pneumonia. A lung biopsy was performed after sputum and thoracentesis
      cultures failed to identify a pathogen. The lung biopsy revealed an
      unidentifiable, diphtheroid-like, gram-positive rod. A bronchoscopy performed
      five days after the lung biopsy produced the same diphtheroid-like, gram-positive
      rod. The patient was treated with several injectable antibiotics, but emergence
      of resistance to two of the antibiotics was suspected. Two weeks after the
      bacterial isolate was sent to a reference laboratory, it was identified as RE.
      The patient was discharged on oral antibiotics and experienced no recurrence of
      RE pneumonia. CONCLUSIONS: RE can be difficult to identify in the microbiology
      laboratory, or it may be assumed to be a colonizing diphtheroid. The isolation of
      difficult-to-identify, gram-positive rods, or diphtheroids, from a pulmonary
      source in a patient with decreased cell-mediated immunity should cause one to
      suspect RE. RE has been noted to develop resistance to beta-lactam antibiotics
      during therapy. A prolonged course of combination antibiotic therapy directed at
      the intracellular component of infection is necessary.

PMID- 8286803
TI  - A practical alternative to conventional aminoglycoside dosing methods.
AB  - OBJECTIVE: One-compartment pharmacokinetic equations are adequate to perform
      clinical dosing adjustments for aminoglycoside monitoring. This article describes
      the Fuller-Goldman (FG) method, an alternative method of aminoglycoside dosage
      adjustment after serum concentrations have been obtained. The FG method uses
      pharmacokinetic principles, but does not use standard pharmacokinetic equations
      (SPE) for aminoglycoside dosage adjustment. A comparison of the FG method to SPE
      is also presented. DATA SOURCES: Information was obtained from pharmacokinetic
      textbooks and references using basic pharmacokinetic concepts. Forty sets of peak
      and trough serum drug concentrations were randomly chosen, retrospectively, from
      routine pharmacokinetic service data. All of the patients were men with a variety
      of infectious diseases and cared for on general surgical and medical floors,
      intensive care units, and a spinal cord injury unit. STUDY SELECTION: No studies
      have previously been published using this dosing method. DATA EXTRACTION: Peak
      and trough data were extracted from routine pharmacokinetic monitoring forms kept
      by the coordinator of the Pharmacokinetic Monitoring Service at the Department of
      Veterans Affairs Medical Center. DATA SYNTHESIS: The FG method is characterized
      by assumptions and limitations similar to those of standard pharmacokinetic
      dosing methods. Forty sets of data were evaluated using both the FG method and
      SPE. These data were analyzed using mean percent differences of projected dosages
      and projected half-lives (t1/2S) as measures of the average magnitude of the
      discrepancy between the two methods. Ninety-five percent confidence intervals for
      mean percent differences also are provided. CONCLUSIONS: The FG method
      overestimated by 10.18 percent the dosage recommendations of the SPE method. This
      method also underestimated t1/2 by 2.96 percent, compared with SPE. The FG method
      is a viable alternative aminoglycoside dosing technique that requires one to use
      learned pharmacokinetic concepts.

PMID- 8286805
TI  - Placebo-controlled trial of intravaginal clindamycin 2% cream for the treatment
      of bacterial vaginosis.
AB  - OBJECTIVE: To compare the safety and efficacy of intravaginal clindamycin 2%
      cream with placebo in nonpregnant women with bacterial vaginosis. DESIGN: A
      randomized, double-blind, placebo-controlled clinical trial. SETTING: Ambulatory
      patients in the general community. PATIENTS: Two hundred fifteen nonpregnant
      outpatients with a diagnosis of bacterial vaginosis were entered into this study.
      Of the 134 evaluable patients, 65 received clindamycin and 69 placebo.
      Demographic parameters were comparable between the two treatment groups.
      INTERVENTION: Study subjects were equally randomized to receive either 5 g of
      clindamycin 2% vaginal cream or placebo cream for seven nights. MAIN OUTCOME
      MEASURES: Clinical and microbiologic follow-up evaluations were scheduled for 5
      10 days and 25-39 days posttreatment. Patients were interviewed about signs and
      symptoms, adverse events, and compliance. Diagnostic examinations were performed.
      RESULTS: Clinical success rates (cure and improvement) occurred in 50 of 65
      patients who received clindamycin (77 percent) and 17 of 69 patients who received
      placebo (25 percent) by the first posttreatment visit (p < 0.001). Microbiologic
      cures or improvement were observed in 59 of the 65 patients treated with
      clindamycin (91 percent) compared with 20 of 69 placebo-treated patients (29
      percent) (p < 0.001). At the end of the study, clinical and microbiologic cures
      or improvement were evident in 45 of 57 (79 percent) and 37 of 57 clindamycin
      treated patients (65 percent), respectively, and 18 of 51 (35 percent) and 14 of
      51 (28 percent) of the placebo-treated patients, respectively. The success rates
      with clindamycin 2% cream were statistically higher than those with placebo. The
      adverse-effect profiles in the two groups were similar and no serious adverse
      effects were reported. Patients who received clindamycin had a statistically
      higher incidence of nonbacterial vaginitis/cervicitis (18.5 vs. 7.5 percent, p =
      0.003). CONCLUSIONS: Intravaginal clindamycin 2% cream appears to be an effective
      and safe treatment of symptomatic bacterial vaginosis in nonpregnant women.

PMID- 8286806
TI  - Correlation of aminoglycoside and vancomycin pharmacokinetic parameters.
AB  - OBJECTIVE: To investigate a correlation between the elimination rate constants
      (Ke) of aminoglycosides (AG) and vancomycin; to investigate the correlation
      between actual Ke and creatinine clearance (Clcr) for AG versus vancomycin; to
      investigate the calculated versus actual Ke for AG and vancomycin; and to
      investigate a correlation between volumes of distribution (Vd) between AG and
      vancomycin. DESIGN: Retrospective data collection. METHODS: Patients in our
      institution who received AGs or vancomycin concomitantly or within six weeks of
      each other were identified retrospectively. Patient subpopulations were
      identified and analyzed collectively as well as individually. Steady-state serum
      concentrations of AG and vancomycin (more than four half-lives) were obtained and
      kinetic parameters (Ke, Vd) were calculated using first-order pharmacokinetic
      equations. Linear regression was used to determine correlation coefficients.
      RESULTS: In the total population and all subpopulations, the correlation between
      Ke of AG and vancomycin was superior to the correlation between Ke and Clcr. The
      correlations (r2) between Ke for AG and vancomycin in the total, general
      medicine, oncology, and intensive care units (ICU) populations were 0.572, 0.878,
      0.349, and 0.561, respectively. The correlations (r2) between Ke and Clcr for AG
      in the total, general medicine, oncology, and ICU populations were 0.235, 0.430,
      0.005, and 0.238, respectively. The correlations (r2) between Ke and Clcr for
      vancomycin in the total, general medicine, oncology, and ICU populations were
      0.300, 0.407, 0.055, and 0.309, respectively. CONCLUSIONS: The correlation
      between Ke of AG and vancomycin may be beneficial for predicting Ke of vancomycin
      when AG concentrations have already been obtained or vice versa, and may give
      more accurate estimations of dosing intervals and require less time adjusting,
      ordering, and interpreting concentrations and dosages.

PMID- 8286807
TI  - Influence of beta carotene, vitamin E, and vitamin C on endogenous antioxidant
      defenses in erythrocytes.
AB  - OBJECTIVE: To evaluate the in vivo radical scavenger activity of vitamin E,
      vitamin C, and beta carotene on erythrocyte membranes. DESIGN: A prospective,
      open trial without placebo. SETTING: Department of Clinical Pharmacy. PATIENTS:
      Ten healthy volunteers being supplemented with beta carotene, vitamin E, and
      vitamin C. MEASUREMENTS: Erythrocytes were incubated in water bath with 2,2'
      azobis (2 amidinopropane) hydrochloride (AAPH). AAPH decomposes spontaneously at
      37 degrees C to generate free radicals inducing membrane cellular damage and
      hemolysis. The absorbance was measured at 405 nm at 0, 30, and 60 min, and then
      every 20 minutes for four hours. The time for 50 percent of maximal hemolysis
      (T50%), which expresses the radical scavenger activity of erythrocytes, was
      determined. RESULTS: The physiologic T50% value determined in 52 healthy
      volunteers is 117 +/- 12 min. Patients receiving these supplements have a higher
      value of T50% (143.2 +/- 11.6 min at 30 d and 145.7 +/- 10.5 min at 60 d) than
      the physiologic value (p < 0.001). CONCLUSIONS: These data suggest that vitamin
      C, vitamin E, and beta carotene stimulate the radical scavenger activity of
      erythrocyte membranes after 30 days.

PMID- 8286808
TI  - Clonidine in panic disorder.

PMID- 8286809
TI  - Nonsteroidal antiinflammatory drugs in menorrhagia.

PMID- 8286810
TI  - Boric acid vaginal suppositories.

PMID- 8286811
TI  - Dronabinol in tremor.

PMID- 8286813
TI  - Cefpodoxime proxetil: a new, broad-spectrum, oral cephalosporin.
AB  - OBJECTIVE: To discuss the chemistry, pharmacokinetics, spectrum of activity,
      clinical trials, adverse effects, drug interactions, and dosage guidelines of
      cefpodoxime proxetil. DATA SOURCES: Literature was identified through a MEDLINE
      search from 1988 to the present and from review of bibliographies in that
      literature. STUDY SELECTION: Data were limited to comparative trials published in
      the English literature. Although many studies were conducted in Japan, the
      results often were available only in Japanese or partly in English. As these
      studies could not be completely evaluated, they are not included in this review.
      DATA SYNTHESIS: Cefpodoxime exhibits good activity against many gram-positive and
      gram-negative organisms. In clinical trials, cefpodoxime was similar in both
      clinical and bacteriologic efficacy to amoxicillin, cefaclor,
      amoxicillin/clavulanate, and penicillin in the treatment of respiratory and
      urinary tract infections. It also appeared effective in the treatment of skin and
      soft tissue infections, although no comparative trials have been performed.
      Cefpodoxime is well tolerated by children and is effective in the treatment of
      otitis media and pharyngitis. It has a similar adverse effect profile to that of
      other penicillins and cephalosporins, with gastrointestinal effects being most
      common. CONCLUSIONS: Cefpodoxime demonstrates good in vitro activity against
      pathogens frequently associated with respiratory tract, urinary tract, and skin
      and tissue infections. It has not demonstrated greater efficacy than the other
      antibiotics to which it has been compared. The available published clinical
      trials are fraught with methodologic, statistical, and evaluative flaws. Thus,
      further trials comparing cefpodoxime with established treatments, as well as the
      newer cephalosporins, are needed before its place in therapy can be established.

PMID- 8286812
TI  - Sotalol: a breakthrough antiarrhythmic?
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetic, dosing, adverse effects,
      and therapeutic uses of sotalol. DATA IDENTIFICATION: Articles were identified
      with an English-language literature computer search via Knowledge Finder, using
      the term sotalol, and with an extensive search of bibliographies of identified
      articles. STUDY SELECTION: Relevant or representative animal studies, human
      trials, and case reports were selected for evaluation. DATA EXTRACTION: The
      literature was assessed for quality, methodology, and outcome information. DATA
      SYNTHESIS: Sotalol is a racemic compound with Class II (beta-blocking properties)
      and Class III (prolonged action potential) antiarrhythmic activity. It has been
      suggested that the plasma concentration associated with QTc prolongation (a
      measure of the Class III action) is much greater than that associated with beta
      blockade. Therefore, sotalol is categorized as a Class III antiarrhythmic agent.
      The 1-isomer is responsible for the beta-blocking activity, whereas both isomers
      have Class III properties. After oral dosing in fasting patients with normal
      renal function, sotalol is > 90 percent absorbed, achieves peak serum
      concentrations in 2-4 h, is excreted unchanged 80-90 percent in the urine, has a
      volume of distribution of 1-2 L/kg, and has an elimination half-life of about 12
      h. Sotalol is effective in patients with life-threatening ventricular arrhythmias
      that have been refractory to other conventional antiarrhythmic drugs. In general,
      sotalol appears to be well tolerated, with many of its adverse effects caused by
      beta-blocking activity. As with other antiarrhythmic agents, the possibility of
      proarrhythmia (frequently torsade de pointes) exists. CONCLUSIONS: Racemic
      sotalol is an effective Class III antiarrhythmic agent approved by the Food and
      Drug Administration for the treatment of documented life-threatening ventricular
      arrhythmias. Investigations continue with racemic sotalol in the management of
      supraventricular arrhythmias. Trials with the d-isomer are also ongoing.

PMID- 8286814
TI  - Bacillary angiomatosis in a patient with AIDS.
AB  - OBJECTIVE: To report the clinical presentation and response to antimicrobial
      therapy of presumed bacillary angiomatosis in an AIDS patient. DESIGN: Single
      case report. SETTING: A 1058-bed, university teaching hospital. PATIENT: 28-year
      old HIV-positive man (T4 lymphocyte count < 3/mm3), who was diagnosed with AIDS
      in 1984. RESULTS: The skin lesions responded promptly to treatment with
      doxycycline and erythromycin. CONCLUSIONS: Bacillary angiomatosis is an infection
      that occurs with endstage AIDS. Skin lesions have recognizable characteristics
      and respond promptly to appropriate antibiotic therapy.

PMID- 8286815
TI  - Drug disposition in neonates with patent ductus arteriosus.
AB  - OBJECTIVE: To review the literature on the physiologic changes created by
      neonatal patent ductus arteriosus (PDA) and the potential impact on drug
      disposition in these infants. DATA SOURCES: An Index Medicus and bibliographic
      search of the English-language literature pertaining to neonatal PDA and drug
      usage in newborns. DATA SYNTHESIS: PDA in premature infants is associated with a
      variety of physiologic changes that could alter drug disposition. Perfusion of
      drug-elimination organs (i.e., liver and kidney) may be diminished, resulting in
      decreased drug elimination. Further, the general fluid overload state associated
      with PDA may result in larger volumes of distribution (Vd), and dilutional
      effects for many drugs. Drug absorption, Vd, tissue penetration, and clearance
      may be affected by the physiologic changes incurred by a PDA. Although the
      pharmacokinetics of several categories of therapeutic agents may be affected by a
      PDA, disposition changes with the aminoglycosides and indomethacin have been the
      best documented. The most reliable pharmacokinetic change appears to be related
      to drug Vd. The interpretation of many of these studies is confounded by a
      potential drug interaction with the concurrent administration of indomethacin for
      PDA closure. CONCLUSIONS: Close therapeutic drug monitoring is indicated in
      newborns with PDAs as abrupt changes in drug disposition can occur with PDA
      closure. PDA-induced changes in specific pharmacokinetic parameters of agents
      such as the aminoglycosides, indomethacin, and perhaps vancomycin may prove to be
      a valuable diagnostic adjunct for the identification of babies with undiagnosed
      PDA. More research into this pharmacophysiologic aspect of pharmacokinetics is
      warranted.

PMID- 8286816
TI  - Reassessing the lower end of the phenytoin therapeutic range: a review of the
      literature.
AB  - OBJECTIVE: To critically review available data on the effective lower end of the
      phenytoin therapeutic range for the treatment of seizure disorders. DATA SOURCES:
      Relevant articles were identified from an English-language search of MEDLINE 1982
      1992. Additional references were found in bibliographies of these articles. STUDY
      SELECTION/DATA EXTRACTION: We reviewed articles that included data on serum
      phenytoin concentrations (SPCs) and seizure control. Data on concurrent
      anticonvulsants, seizure diagnosis, and seizure severity were extracted when
      available. DATA SYNTHESIS: The original study defining the phenytoin therapeutic
      range as 10-20 mg/L is analyzed; it was based on a small, homogeneous sample that
      cannot be generalized to a more diverse epileptic population. Many studies report
      patients obtaining seizure control with SPCs below 10 mg/L. Studies including a
      range of seizure diagnoses and severity have a larger variability in effective
      SPCs; however, effective SPCs are reproducible. CONCLUSIONS: The therapeutic
      range of phenytoin is defined on an individual basis. Some patients, especially
      those with infrequent, primary tonic-clonic seizures, may be controlled with
      phenytoin concentrations below the recognized reference range of 10-20 mg/L.

PMID- 8286817
TI  - Assessing physician choice of nonsteroidal antiinflammatory drugs in a health
      maintenance organization.
AB  - OBJECTIVE: To develop a categorization scheme for grouping various nonsteroidal
      antiinflammatory drugs (NSAIDs) by relative safety; to develop a method to
      quantify the appropriateness of the initial and subsequent choices of NSAID
      therapy; to assess whether NSAID prescribing was consistent with the developed
      criteria; to examine the cost of inappropriate, acute NSAID use as defined by the
      established criteria. DESIGN: Retrospective drug utilization review focusing on
      NSAIDs. SETTING/PARTICIPANTS: Members aged > or = 18 years of a 40,000-person
      southeastern Michigan health maintenance organization. MAIN OUTCOME MEASURES: (1)
      Appropriateness of therapy using a four-level safety classification system for
      the NSAIDs developed by a consensus process; criteria based on safety under the
      assumption that any particular NSAID is equally likely to be effective when dosed
      appropriately; (2) evaluation of progression of NSAID therapy using the NSAID
      Therapy Progression Formula. RESULTS: For acute patients, almost half of the
      prescriptions were for ibuprofen and 33 percent were for naproxen. Ibuprofen
      usage accounted for 16 percent of total NSAID cost and naproxen agents accounted
      for over 50 percent of that cost. Potential cost savings of approximately $82,000
      probably would have occurred had a 50 percent interchange rate for ibuprofen been
      acceptable. For chronic patients, 85 percent were treated with one or two NSAIDs;
      treatments were of reasonable high quality when compared by safety profiles.
      There was low use of ibuprofen in patients who only received one NSAID.
      CONCLUSIONS: NSAID usage assessment in a large population was achieved by
      developing a classification and scoring system based on NSAID safety; in this
      population, prescribing patterns were generally consistent with established
      criteria; however, when considering cost, improvement in initial NSAID selection
      for acute patients was possible.

PMID- 8286818
TI  - Moving on.

PMID- 8286819
TI  - Faculty development.

PMID- 8286820
TI  - Ciprofloxacin-induced anaphylactoid reaction in a patient with AIDS.

PMID- 8286821
TI  - Potential terfenadine-fluoxetine interaction.

PMID- 8286822
TI  - Enalapril-induced hepatotoxicity.

PMID- 8286823
TI  - Documenting pharmacists' activities in the health record: a mechanism to provide
      ongoing quality assurance.

PMID- 8286824
TI  - Comment: ventricular fibrillation and anoxic encephalopathy secondary to
      astemizole overdose.

PMID- 8286825
TI  - Comment: natural products and the athlete: facts and folklore.

PMID- 8286826
TI  - Expression of c-myc, c-Ki-ras and c-Ha-ras oncogene products in peripheral blood
      mononuclear cells from patients with myasthenia gravis.
AB  - The oncogene products of c-myc, c-Ki-ras and c-Ha-ras and the subsets of natural
      killer cells in the peripheral blood mononuclear cells (PBMC) from 39 patients
      with myasthenia gravis (MG) and 40 healthy individuals were studied by
      immunocytochemical procedures. The MG patients showed an increased expression of
      c-myc, c-Ki-ras and c-Ha-ras oncoproteins in both lymphocytes and monocytes
      compared to those of healthy individuals (P < 0.01, P < 0.005 and P < 0.001,
      respectively). On the contrary, the number of Leu-7-Leu-11c+ cells of MG patients
      was less than that of healthy controls (P < 0.05). The oncogene expressions in
      PBMC of MG patients correlated positively with white blood cell counts, total
      natural killer cell counts (NK), Leu-7+Leu-11c+ of NK cell subset, gamma
      globulin, erythrocyte sedimentation rate and serum immunoglobulins; the oncogene
      expressions were negatively correlated with the Leu-7+Leu-11c-NK subset. Thus,
      the increased expressions of c-myc, c-Ki-ras and c-Ha-ras oncoproteins
      accompanying the decreased Leu-7-Leu-11c+NK cell in MG PBMC are likely
      responsible for the acceleration of the clinical manifestations in MG patients.

PMID- 8286828
TI  - Headache and painful lymphadenopathy in extracranial or systemic infection:
      etiology of new daily persistent headaches.
AB  - From 108 cases of new daily persistent headaches, clinical or laboratory evidence
      was found suggesting extracranial or systemic infections in: 28 cases (25.9%) of
      gastrointestinal mainly Salmonella, 28 (25.9%) urinary Coli, 16 (14.8%)
      Streptococcal, 4 (3.7%) each of Epstein Barr virus or Toxoplasma, and 1 (0.9%)
      each of Herpes Zoster or pneumonia. A group of 26 (24.1%) showed high Proteus OX
      titer or clinical adenoviral involvement. All had normal neurological
      examinations plus selective negative neuroimaging or spinal taps. The mean
      headache duration was 13.8 days, and mean age 28.8 years. Prominent symptoms were
      fever in 37 (34.2%) cases, nausea/vomiting in 30 (27%) and vertigo in 17 (15.7%).
      Diarrhea, dysuria, and abdominal discomfort were rare. Headache was a solitary
      symptom in 36 (33.3%). The predominant sign was painful cervical lymphadenopathy
      in 61 (56.5%). These cases represent 1.2% of our 9060 neurology patients.

PMID- 8286827
TI  - Appropriate interferon-alpha therapy for chronic hepatitis C: an assessment by
      quantitative changes in serum hepatitis C virus-RNA.
AB  - The antiviral effect of natural interferon (IFN)-alpha on chronic hepatitis C
      virus (HCV) infection was estimated by determining quantitative changes in serum
      HCV-RNA compared with the serum alanine aminotransferase (sALT) improvement; the
      relationships of responses to IFN according to the dose and period of IFN therapy
      were defined to determine an appropriate IFN therapy protocol. Twenty-two
      patients with chronic hepatitis C were given natural IFN-alpha and in 16 (72.7%)
      patients the viraemia was suppressed during therapy. Five (27.7%) of them
      sustained the disappearance of HCV-RNA for more than 6 months after therapy
      accompanied with a prolonged sALT improvement. Pre-treatment viraemia levels in 5
      complete responders with "complete suppression" of viraemia were significantly
      lower than in 11 patients with a transient loss or a decline of HCV-RNA. A
      favorable antiviral response was closely associated with a high total dose of IFN
      alpha and a long duration of IFN therapy.

PMID- 8286829
TI  - Myelo-monocytoid immunophenotypes of B-cell chronic lymphocytic leukemia cells.
AB  - Leukemia cells from ten patients with B-cell chronic lymphocytic leukemia (B-CLL)
      and one with B-CLL of mixed cell type (B-CLL/PL) were analyzed to delineate the
      cellular characteristics, especially the myelomonocytic nature. Most of the
      surface phenotypes were consistent with the previous reports. However, the
      frequency of positivity for CD22 and CD25 was much higher in the examined cases
      of B-CLL than in Western reports. B-CLL cells frequently possessed antigens which
      are mainly expressed in myelomonocytic cells: 8/10 for CD11b and 4/10 for CD11c,
      although the presence of CD14 was not apparent (0/10). In addition, colony
      stimulating factor-1 receptors (CSF-1R) were expressed in 6 of the 10 B-CLL
      cases. The reactivity with antigens such as CD14, CD11c, and CSF-R was markedly
      enhanced by in vitro incubation. Alterations in antigen expression and in in
      vitro survival by growth factors for myelomonocytic lineage were observed in
      certain cases. These data imply that not only are B-CLL cells phenotypically
      closely related to myelomonocytic lineage but that they may also be influenced by
      growth factors for that lineage.

PMID- 8286830
TI  - Protothecosis in a patient with systemic lupus erythematosus.
AB  - A rare case of protothecosis in a 40-year-old Japanese woman with systemic lupus
      erythematosus, under long-term prednisolone treatment is presented. The patient
      developed extensive ulcerative skin lesions after injury. The characteristic
      histopathological findings and biochemical sugar assimilation tests indicated
      infection by Prototheca wicherhamii. The lesions improved following treatment
      with amphotericin B. The immunodeficient state of this patient seemed to
      contribute to the infection with Prototheca.

PMID- 8286831
TI  - Biloma during steroid therapy for minimal change nephrotic syndrome.
AB  - A 27-year-old man, who had been on steroid therapy for 2 months for his nephrotic
      syndrome, suddenly developed intra-abdominal bile collection (biloma). He had no
      previous history of abdominal surgery, trauma, or any disease of the
      hepatobiliary system. The cause of the biloma formation was due, probably, to
      cholecystitis in the absence of calculi and a pinhole size perforation in the
      wall of gall bladder. It was assumed to be closely related to the high-dose
      steroid therapy over a prolonged period, which would likely suppress the repair
      process of the locally damaged biliary system.

PMID- 8286832
TI  - Fatal acute hepatitis B virus infection while receiving immunosuppressants after
      renal transplantation.
AB  - A 47-year-old man with acute hepatitis B virus (HBV) infection who had been
      receiving immunosuppressants after renal transplantation developed progressive
      liver failure. During the clinical course (approximately 7 months), anti-HBc IgM
      antibody and HBV-DNA polymerase levels remained high, but the serum alanine
      aminotransferase (ALT) level was consistently less than 150 K.U. Histopathologic
      examination of the liver showed submassive hepatic necrosis without significant
      inflammation accompanied by marked fibrosis. Most hepatocytes showed strong
      nuclear expression of HBc antigen by immunohistochemical staining and electron
      microscopy revealed numerous intranuclear core-like particles. Hepatitis B virus
      infection in immunosuppressed individuals occasionally insidiously progresses,
      resulting in liver failure. The clinical course of such patients thus merits
      close scrutiny.

PMID- 8286833
TI  - Idiopathic sclerosing peritonitis in a man.
AB  - Idiopathic sclerosing peritonitis (ISP) is a rare condition which has been mainly
      reported in young adolescent women as a cause of small bowel obstruction. In
      these patients the small bowel is sometimes encased in a fibrous sac called an
      "abdominal cocoon". We describe a 62-year-old man who underwent exploratory
      laparotomy for ascites and abdominal mass. Laparotomy showed 5.4 l of ascites and
      the entire small bowel was encased in a fibrous sausage-like cocoon. The
      pathological findings were characteristic of sclerosing peritonitis.

PMID- 8286834
TI  - Crow-Fukase syndrome associated with pulmonary hypertension.
AB  - A 60-year-old woman suffering from heart failure was found to have Crow-Fukase
      syndrome. A precise cardiovascular study revealed the existence of pulmonary
      hypertension (PH), cardiomegaly and myocardial hypertrophy in addition to
      manifestations of this syndrome such as hyperpigmentation, hypertrichosis, finger
      clubbing, polyneuropathy, organomegaly and plasma cell dyscrasia. These findings
      suggest the possibility that patients with Crow-Fukase syndrome have
      cardiopulmonary disorders including PH and cardiomegaly which might cause some
      cardiovascular symptoms such as peripheral edema and finger clubbing.

PMID- 8286835
TI  - Primary Sjogren's syndrome with subcortical dementia.
AB  - A 48-year-old man with primary Sjogren's syndrome (P-SS) developed subcortical
      dementia, characterized by forgetfulness, poor attention and concentration,
      slowness of thought process, difficulty to manipulate acquired knowledge,
      introversive and hostile personality change and inactivity. These were improved
      by corticosteroid treatment. Magnetic resonance imaging (MRI) revealed small
      lesions in the subcortical and periventricular white matter. An
      electroencephalogram (EEG) revealed short runs of theta activities in bilateral
      parietal areas. Latency of P300 shortened in accordance with clinical
      improvement. These findings suggest that the cognitive and neuropsychiatric
      manifestations in P-SS are included in a spectrum of organic brain dysfunction
      and are treatable.

PMID- 8286836
TI  - Integrin VLA-5 negative primary plasma cell leukemia.
AB  - We present a case of primary plasma cell leukemia with Bence Jones proteinuria.
      After combination chemotherapy, leukemic cells and the urinary levels Bence Jones
      protein were decreased. Small lytic bone lesions were detected only in the skull.
      Typical plasma cells were rarely seen in peripheral blood on the hyperleukocytic
      phase, however they were increased in the advanced stages. The most important
      diagnostic sign was persistent expression of CD38 antigen on leukemic cells
      throughout the entire course of the illness and these leukemic cells expressed
      very late antigen-4 (VLA-4) but not VLA-5.

PMID- 8286837
TI  - Cerebral cysticercosis.
AB  - A 44-year-old female underwent a right frontal craniotomy under a diagnosis of
      metastatic brain tumor and a fluid-filled cystic lesion was extirpated. One rice
      grain sized nodule was identified in the cyst and histopathological examination
      of the nodule showed a scolex with hooks and suckers. These macro and microscopic
      findings indicated a diagnosis of cerebral cysticercosis, caused by infection of
      the larval stage of some type of Taenia species. A therapeutic course of
      praziquantel was given after craniotomy. The patient has been a resident of the
      Kanto area of Japan since birth and has never been outside Japan.

PMID- 8286838
TI  - Metabolic bone disease (anticonvulsant osteomalacia) and renal tubular acidosis
      in tuberous sclerosis.
AB  - The characteristics triad of tuberous sclerosis-adenoma sebaceum, mental
      deficiency and epilepsy-associated with distal-type renal tubular acidosis was
      combined with anticonvulsant osteomalacia in a 41-year-old woman. In addition to
      the specific bone lesions of tuberous sclerosis, the bone disease was caused by
      an adverse effect of a drug and possibly also by the renal disorder leading to
      significant musculoskeletal disability. In response to calcium carbonicum and 1
      25-dihydroxyvitamin D therapy the musculoskeletal disability healed and the
      abnormal biochemical markers of anticonvulsant osteomalacia disappeared. The
      present observation draws attention to the increased hazard threatening patients
      on chronic anticonvulsant therapy simultaneously suffering from renal diseases.

PMID- 8286839
TI  - Hepatitis in an adult with rubella.
AB  - Rubella was accompanied by hepatic dysfunction in a 28-year-old male. Serum
      aminotransferase levels were moderately elevated and LDH markedly increased,
      especially LDH isoenzyme 5, whereas total bilirubin and ALP remained almost
      normal. GOT, GPT and LDH levels were completely normalized by the 21st hospital
      day. Paired antibody titers of viruses which may cause hepatitis, other than
      rubella, were of no significance. Laparoscopy showed enlarged, red liver.
      Histologic and electron microscopic findings of the liver were consistent with
      acute hepatitis. Hepatic damage with rubella is rare, and it is possible that the
      hepatic dysfunction seen in adult rubella may be mediated by an immunopathologic
      mechanism.

PMID- 8286840
TI  - Acute lymphoblastic leukemia associated with a t(1;19)(q23;p13) in an adult.
AB  - A cytogenetic study of a 38-year-old patient with acute lymphoblastic leukemia
      (ALL) revealed a t(1;19)(q23;p13), which is a characteristic translocation of
      childhood ALL. The leukemic cells were positive for the CD10, CD19, HLA-DR, TdT
      and cytoplasmic mu-chain. Both of the immunoglobulin heavy chain gene loci were
      rearranged and the RNA-based polymerase chain reaction demonstrated the E2A/PBX1
      fusion transcript which is the result of the t(1;19). This finding suggests that
      the t(1;19) is implicated not only in childhood ALL but also in adult ALL
      patients.

PMID- 8286841
TI  - Reversible left ventricular diastolic dysfunction resulting from frequent
      supraventricular tachycardia.
AB  - In two patients with frequent supraventricular tachycardia, echocardiograms
      revealed remarkable left ventricular systolic and diastolic dysfunction,
      associated with an absence of left ventricular filling during the early diastolic
      phase. This dysfunction was detected during normal sinus rhythm as well as
      tachycardia. By treatment with propafenone, both patients showed dramatic and
      rapid improvement of symptoms and the left ventricular dysfunction. Left
      ventricular diastolic dysfunction as well as systolic dysfunction were detected
      in patients with supraventricular tachycardia, suggesting that frequent
      supraventricular tachycardia results in severe left ventricular diastolic
      dysfunction which is reversible after control of the tachycardia.

PMID- 8286842
TI  - Ultrastructure and function of cilia and spermatozoa flagella in a patient with
      Kartagener's syndrome.
AB  - A 37-year-old man with the characteristic clinical signs of Kartagener's
      syndrome, including bronchiectasia, chronic paranasal sinusitis, and situs
      inversus, was found to have immotile cilia and sperm. Electron microscopy
      demonstrated that the majority of cilia lacked dynein arms and radial spokes and
      that various defects of microorgans existed in the sperm. The most frequent
      defect was total defect of axoneme followed by defect of inner dynein arms in the
      sperm. These findings suggest an association between the structural abnormality
      of absent inner dynein arms and immotility of cilia and sperm in Kartagener's
      syndrome.

PMID- 8286843
TI  - Cytomegalovirus mononucleosis with mixed cryoglobulinemia presenting transient
      pseudothrombocytopenia.
AB  - A 61-year-old man was admitted to our hospital because of fever and general
      malaise. We diagnosed his condition as cytomegalovirus (CMV) mononucleosis by
      hematological testing. His platelet count was decreased in spite of collection
      with several anticoagulants at room temperature (20 degrees C); no decrease was
      observed at 37 degrees C. Mixed cryoglobulinemia, monoclonal IgM and polyclonal
      IgG, which acted as anti-platelet antibodies in cold condition, were found in the
      patient's serum. With the resolution of CMV infection, the cryoglobulins
      disappeared and the platelet count returned to normal without platelet
      agglutination. This is the first report of transient pseudothrombocytopenia in
      CMV mononucleosis with mixed cryoglobulinemia.

PMID- 8286844
TI  - Marked increase in fundic mucosal histidine decarboxylase activity in a patient
      with H+,K(+)-ATPase antibody-positive autoimmune gastritis.
AB  - A 63-year-old woman was diagnosed as autoimmune gastritis by the presence of
      serum antibody against alpha-subunit of gastric H+,K(+)-ATPase. The patient did
      not have pernicious anemia, but showed achlorhydria, marked hypergastrinemia,
      enterochromaffin-like cell hyperplasia and an extremely high histidine
      decarboxylase activity in the gastric fundic mucosa. Intragastric acidification
      by infusion of hydrochloric acid via a nasogastric tube induced a transient
      reduction of serum gastrin level and fundic mucosal histidine decarboxylase
      activity. A marked increase in fundic mucosal histidine decarboxylase activity as
      well as hypergastrinemia appears to be the pathophysiologic response to
      achlorhydria caused by autoimmunity against gastric H+,K(+)-ATPase.

PMID- 8286845
TI  - Response to octreotide of intestinal pseudoobstruction and pneumatosis cystoides
      intestinalis associated with progressive systemic sclerosis.
AB  - Intestinal pseudoobstruction and pneumatosis cystoides intestinalis are uncommon
      complications of progressive systemic sclerosis. We report a 26-year-old woman
      with this disorder who responded poorly to conventional treatment. Subcutaneous
      administration of octreotide, a long-acting somatostatin analogue, at a dose of
      50 micrograms/day for 3 weeks, relieved symptoms such as nausea and bloating.
      There was also a marked decrease of intestinal gas accumulation, as documented on
      X-ray films.

PMID- 8286846
TI  - Transcription from TATA-less promoters: dihydrofolate reductase as a model.
AB  - The promoters of many of the genes encoding the so-called "housekeeping" enzymes,
      oncogenes, growth factors and their receptors, and transcription factors, do not
      contain a canonical TATA box, which is known to direct transcription initiation.
      The mechanisms through which TATA-less promoters are regulated, and their
      transcription start sites selected, have begun to yield to investigation. Using
      the dihydrofolate reductase (DHFR) gene as a model, recent work on this group of
      genes has been reviewed. Control of transcription initiation and the role of
      "initiator" sequences, as well as their binding factors, in particular YY1 and
      E2F, are addressed. In the DHFR gene, neither the E2F site at the major
      initiation region nor the upstream Sp1 sites can alone produce wild-type
      initiation, despite the fact that each of these sites has certain properties of
      initiators. Many TATA-less genes are growth regulated, that is, transcription is
      increased in response to stimulation of cell proliferation. Although both Sp1 and
      E2F have been implicated in growth regulation, our recent studies suggest that
      Sp1 sites alone can confer a growth-dependent increase in transcription in the
      late G1 and early S phases of the cell cycle. The regulatory role of E2F, which
      binds to many TATA-less promoters and mediates viral stimulation of
      transcription, is also reviewed.

PMID- 8286847
TI  - Replitase: a complex integrating dNTP synthesis and DNA replication.
AB  - Replitase is a multienzyme complex of mammalian cells that produces
      deoxynucleoside triphosphates and delivers them to the DNA polymerase activity,
      which also resides in the complex. Structural interactions within this complex
      form the basis of internal controls to keep these key biosynthetic processes
      efficient and in balance. The active complex is formed in the nuclear region in
      only the S phase of the cell cycle, when the cell's DNA is being replicated.
      Replitase is a member of the growing family of structured, multienzyme,
      biosynthetic complexes for which very similar complexes are found in prokaryotes
      and eukaryotes. Logically, the most basic of all biosynthetic pathways should
      show the efficiency and precise controls that even lesser pathways possess and,
      in fact, this seems to be so. In this article, we have outlined a broad range of
      evidence supporting the existence of the replitase complex in mammalian cells, a
      complex for dNTP synthesis and polymerase that exists only in the S phase and
      only in the nuclear region. This is consistent with localization studies in
      intact cells and after various forms of cell fractionation and, particularly,
      with experiments of incorporation of precursors into DNA in isolated complexes
      and S phase permeabilized cells. A most forceful argument for replitase is the
      existence of three striking phenomena--channeling, compartmentation, and cross
      inhibition. These are very difficult, perhaps impossible, to explain without
      replitase; with replitase, their explanation is beautifully simple.

PMID- 8286848
TI  - Signaling pathways for vitamin D-induced differentiation: implications for
      therapy of proliferative and neoplastic diseases.
AB  - The physiological form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 (1,25D3) is
      not only a powerful regulator of calcium homeostasis but also a hormone with
      important roles in cell growth and differentiation. The differentiating effects
      of 1,25D3 have been studied extensively in a large number of in vitro systems but
      primarily using cultured leukemia cells, keratinocytes, and bone cells. In spite
      of this attention, the understanding of the mechanisms that lead to the diverse
      forms of cell differentiation by 1,25D3 is fragmentary. It seems likely, however,
      that the effects of 1,25D3 on calcium homeostasis and on cell differentiation are
      both signaled by direct effects on the cell membrane and by the transduction of
      the signal to the genome. The direct effect may be mediated by a hypothetical
      membrane recognition element, the G proteins, phosphoinositide metabolism, and
      protein kinase C (PKC). Signals to the nucleus may include PKC, the Ca2+
      gradient, and protein phosphorylation cascades, but the protein receptor (VDR)
      plays a principal role in this form of signal transduction. The VDR interacts
      with the promoter elements of a number of nuclear genes, either as a homodimer or
      a heterodimer with a retinoid or orphan receptors. The key nuclear responses
      include the increased expression of phenotype-specifying proteins and the
      appearance of G1/S and G2+M cell cycle blocks, which result in cessation of cell
      proliferation. The attempts to improve control of neoplastic cell proliferation
      will depend on a selective exploitation of these properties of 1,25D3 to design
      novel analogs of 1,25D3 with low hypercalcemic but high differentiation-inducing
      properties. It is anticipated that a better understanding of the multiple
      pathways that transduce the signals from 1,25D3 to the nucleus and to the cell
      membrane, a consideration of the structure-function relationships of the
      derivatives of 1,25D3, and the use of synergistic combinations of 1,25D3 with
      other biological response modifiers or cytotoxic drugs will lead to improved
      therapy of several hyperproliferative and malignant diseases.

PMID- 8286849
TI  - Tailor made sialidase inhibitors home in on influenza virus.

PMID- 8286850
TI  - Do alcohol and complex carbohydrates mix?

PMID- 8286851
TI  - Immunological-based assay methods for glycosyltransferase enzymes.

PMID- 8286852
TI  - Re: Conservation and evolution of glycosylation sites on immunoglobulin-type
      domains.

PMID- 8286853
TI  - Substrate specificity of peptide:N-glycosidase from Flavobacterium
      meningosepticum.

PMID- 8286854
TI  - The carbohydrate-deficient glycoprotein syndromes: pre-Golgi and Golgi disorders?
AB  - The carbohydrate-deficient glycoprotein syndromes are a recently delineated group
      of genetic, multisystemic diseases with major nervous system involvement. Three
      distinct variants have been recognized and there are probably many more. They are
      characterized by a deficiency of the carbohydrate moiety of secretory
      glycoproteins, lysosomal enzymes and probably also membranous glycoproteins. The
      biochemical changes are most readily observed in serum transferrin and the
      diagnosis is usually made by isoelectric focusing of this glycoprotein. The
      deficiency of sialic acid, in particular, results in a cathodal shift and hence
      the presence of abnormal isoforms of transferrin with higher isoelectric points
      than normal. The basic defects are probably in the processing and synthesis of
      the carbohydrate moiety of glycoproteins; there is indirect evidence for a
      deficiency of asparagine-N-linked oligosaccharide transfer in type I (endoplasmic
      reticulum defect) and for a deficiency of N-acetylglucosaminyltransferase II in
      type II (Golgi defect). From the large number of patients detected in only a few
      years, it is expected that these diseases will become as important as, for
      example, the lysosomal, peroxisomal or mitochondrial disorders. Their study will
      undoubtedly yield a wealth of new information on the function of glycoproteins
      and of their carbohydrate moiety.

PMID- 8286855
TI  - Glycosylation sites identified by solid-phase Edman degradation: O-linked
      glycosylation motifs on human glycophorin A.
AB  - The human red blood cell sialoglycoprotein, glycophorin A (GpA), contains a
      'mucin-like' extensively O-glycosylated extracellular domain which carries the MN
      blood group antigens. We have revised the sites of O-glycosylation in the
      extracellular domain of GpA by automated solid-phase Edman degradation, which
      allowed positive identification and quantitation of O-glycosylated Ser and Thr
      residues, as well as the single N-glycosylation site. One N-linked and 16 O
      linked sites were identified. Carbohydrate was absent on Ser1, Ser14, Ser15,
      Ser23, Thr28 and Thr58 in GpA. We propose that the glycosyltransferases present
      in erythrocytes recognize specific flanking sequences around potential O
      glycosylation sites. All 16 O-glycosylation sites are explained on the basis of
      four motifs. Three motifs are associated with Thr-glycosylation: Xaa-Pro-Xaa-Xaa
      where at least one Xaa = Thr; Thr-Xaa-Xaa-Xaa where at least one Xaa = Thr; Xaa
      Xaa-Thr-Xaa where at least one X = Arg or Lys. The fourth motif is associated
      with Ser-glycosylation: Ser-Xaa-Xaa-Xaa where at least one Xaa = Ser. These
      simple rules explain the glycosylation (or lack of it) on 21 of 22 Ser/Thr in the
      extracellular domain of GpA.

PMID- 8286856
TI  - Rotaviruses preferentially bind O-linked sialylglycoconjugates and sialomucins.
AB  - Rotaviruses are the most common cause of severe gastroenteritis in infants and
      children worldwide. Early events of virus binding and entry are the critical
      determinants of cellular permissiveness to rotavirus replication. The only known
      ligands for rotaviruses are sialic acids. We now report that simian rotaviruses
      bind preferentially to a subset of sialylated glycoconjugates, i.e. glycoproteins
      containing O-linked sialic acid moieties. Rotaviruses are able to distinguish
      between sialylated trisaccharide ligands presented as neoglycolipids. Higher
      avidity binding by rotaviruses is explained by multivalent binding to clustered
      sialic acid moieties. Our in vitro data are extended to explain the protective
      effect of mucins in the murine model of rotavirus disease and the specific
      binding by rotavirus to a high molecular weight sialomucin in the infant mouse
      intestine. Rotavirus binding to a sialomucin may be analogous to selectin
      mediated mechanisms of cellular adhesion, and may be advantageous to the virus in
      the dynamic environment of the intestine.

PMID- 8286857
TI  - Lectin-induced apoptosis of tumour cells.
AB  - The mechanisms of cytotoxic activity of Griffonia simplicifolia 1-B4 (GS1B4) and
      wheat germ agglutinin (WGA) lectins against various murine tumour cell lines were
      studied. Tumour cells that lack lectin-binding carbohydrates were resistant to
      lysis by these lectins. However, YAC-1 cells that expressed GS1B4 lectin-binding
      sites showed low sensitivity to lysis. To further analyse the relative importance
      of cell surface carbohydrates in lectin cytotoxicity, BL6-8 melanoma cells, which
      do not express the alpha 1,3 galactosyltransferase (alpha 1,3GT) gene and cell
      surface alpha-galactosyl epitopes reacting with GS1B4 lectin, were transfected
      with cDNA encoding alpha 1,3GT. After transfection, BL6-8 cells expressed high
      levels of GS1B4-binding alpha-galactosyl epitopes, but remained resistant to
      lysis by GS1B4 lectin, suggesting that the presence of lectin-binding epitopes,
      while essential, is not sufficient for tumour cell lysis and probably some
      intracellular mechanisms are involved in the regulation of lectin-mediated
      cytotoxicity. We found that the GS1B4 and WGA lectins induced apoptosis with DNA
      fragmentation of sensitive, but not resistant, tumour cell lines. DNA
      fragmentation, as well as tumour cell lysis, was blocked in the presence of the
      specific inhibitory sugar. To determine whether binding of the lectin to cell
      surface carbohydrates is sufficient to trigger tumour cell lysis, lectin
      sensitive CL8-1 melanoma cells were incubated with GS1B4 lectin immobilized on
      agarose beads. Although these tumour cells bind to the immobilized lectin, it
      failed to trigger tumour cell death, suggesting that only soluble lectin is
      capable of tumour cell lysis and lectin internalization is probably required for
      their lysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286858
TI  - Isolation and properties of a soluble sialidase from the culture fluid of Chinese
      hamster ovary cells.
AB  - A soluble sialidase that can degrade recombinant glycoproteins expressed in
      Chinese hamster ovary (CHO) cells has been isolated and purified to near
      homogeneity from the cell culture fluid of this host. Purification of
      approximately 34,000-fold was carried out using conventional purification
      techniques including sequential DEAE-Sepharose and S-Sepharose ion-exchange
      chromatography, followed by hydrophobic interaction chromatography with Phenyl
      Toyopearl. Final purification was achieved by heparin-agarose and
      chromatofocusing chromatography. The minimum molecular weight of the sialidase on
      SDS-PAGE was approximately 43,000 Da. When the final preparation was examined
      under non-denaturing conditions, two major (pI = 6.8 and 7.0) and five minor
      electrophoretic forms with different isoelectric points were identified. The
      basis for the electrophoretic heterogeneity is not known, but it was not due to
      carbohydrate diversity since no carbohydrates were detected on the purified
      protein. The enzyme degraded a variety of sialyl-conjugate substrates, at a pH
      optimum of 5.9, including intact glycoproteins, oligosaccharides and gangliosides
      with a 4-fold preference for 2,3- versus 2,6-linked sialic acid residues. With
      ganglioside substrates, internally linked sialic acid residues were not cleaved
      by the enzyme. Delineation of this enzyme from the lysosomal and plasma membrane
      sialidases was made using inhibition studies with C-9 substituted 5-acetamido-2,6
      anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2- enonic acid derivatives. The
      enzyme was identified in several CHO cell lines by immunoblotting using antiserum
      raised against a synthetic peptide based on amino acid sequence of a fragment
      derived by trypsin digestion of the purified sialidase.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8286859
TI  - Glycosylation pattern and processing of envelope gene products encoded by
      glycosylation mutants of Friend spleen focus-forming virus.
AB  - The protein encoded by the envelope gene of Friend spleen focus-forming virus is
      responsible for the acute leukaemogenicity of this virus. In order to correlate
      glycosylation and intracellular processing of this protein with viral
      pathogenicity, envelope gene products of pathogenic and apathogenic glycosylation
      mutants were expressed in Rat-1 cells and metabolically labelled with [6
      3H]glucosamine. Following immunoprecipitation, primary and secondary gene
      products (gp55, gp65) were separated by preparative polyacrylamide gel
      electrophoresis. Oligosaccharides were released from tryptic glycopeptides by
      treatment with endo-beta-N-acetylglucosaminidase H (gp55), peptide-N4-(N-acetyl
      beta-glucosaminyl)asparagine amidase F (gp65) or by reductive beta-elimination.
      Resulting glycans were characterized by co-chromatography with authentic
      oligosaccharide standards using different HPLC systems and digestion with
      exoglycosidases. The results revealed that the primary envelope gene products of
      pathogenic glycosylation mutants were, in part, further processed in Rat-1 cells
      similar to wild-type glycoprotein, resulting in polypeptides carrying complex
      type N-glycans as well as partially sialylated O-linked oligosaccharides. In
      contrast, corresponding glycoproteins encoded by apathogenic mutants were found
      to remain at the level of the primary translation product exclusively comprising
      high-mannose-type N-glycans. Hence, intracellular maturation of the envelope gene
      products in this model cell line seems to correlate with the in vivo
      pathogenicity of the glycosylation mutants studied.

PMID- 8286860
TI  - Cell cycle-specific growth inhibition of human breast cancer cells induced by
      metabolic inhibitors.
AB  - Proliferation of exponentially growing breast cancer cells (line Hs578T) was
      blocked specifically in G1 by 3-hydroxy-3-methylglutaryl Coenzyme A (HMG CoA)
      reductase inhibition, as well as by inhibition of N-linked glycosylation. As a
      consequence of these inhibitory conditions, the cells were synchronized in the G1
      stage of the cell cycle. The similarities in the kinetic responses point to the
      possibility that the two different types of metabolic inhibitions block cell
      cycle progression by common mechanisms. One possibility is that the inhibition of
      HMG CoA reductase activity also leads to a depressed rate of N-linked
      glycosylation, which in turn may constitute the critical event for cell cycle
      progression and cell growth. In order to investigate whether this relationship
      exists in breast cancer cells, cells synchronized in G1 by mevinolin (an
      inhibitor of HMG CoA reductase) were used. Upon addition of mevalonate, whose
      endogenous synthesis is catalysed by HMG CoA reductase, the cells entered S phase
      after a 4 h pre-replicative period. Mevalonate stimulation also led to a rapid
      and substantial increase in N-linked glycosylation, measured by determining the
      uptake of radioactive glucosamine. This metabolic event was found to be of
      critical importance for the initiation of DNA synthesis. However, as soon as the
      cells had entered S phase, they were independent of the level of N-linked
      glycosylation.

PMID- 8286861
TI  - Mutants in dolichol synthesis: conversion of polyprenol to dolichol appears to be
      a rate-limiting step in dolichol synthesis.
AB  - Chinese hamster ovary (CHO) cells of the Lec9 recessive complementation group
      display a distinctive profile of resistance to a variety of toxic lectins. In
      addition, they accumulate cis-alpha-unsaturated polyprenol and use mainly
      polyprenol rather than dolichol to synthesize the glycosylated lipids used in
      asparagine-linked glycosylation of proteins. The primary defect in these cells is
      thought to result from a deficiency in polyprenol reductase activity. Three new
      mutants were isolated and determined to have qualitatively, although not
      quantitatively, similar lectin resistance profiles to Lec9 cells. Two of these
      mutants (AbrR and RicR) also contained polyprenol rather than dolichol. The
      lectin resistance profile of an independent mutant which accumulates polyprenol,
      F2A8, was also found to be qualitatively similar to the Lec9 pattern. The
      relationship among these mutants was analysed in more detail by construction of
      cell-cell hybrids. Lectin resistance profiles of the hybrids demonstrated that
      AbrR, RicR and F2A8 fell into the Lec9 complementation group. Analysis of prenols
      in the hybrids also showed that F2A8 was a member of the Lec9 group.
      Surprisingly, a significant fraction of the prenols found in Lec9 x Parent
      hybrids was polyprenol (up to 30% of the neutral fraction), whereas the prenols
      found in Parent x Parent hybrids were nearly exclusively dolichol (97% of the
      neutral lipid fraction). Therefore, reduction of polyprenol to dolichol appears
      to be a rate-limiting step in the synthesis of dolichol since hybrids with
      differing numbers of wild-type alleles can be biochemically distinguished.

PMID- 8286862
TI  - Phosphorylation and subcellular location of alpha-L-fucosidase in lymphoid cells
      from patients with I-cell disease and pseudo-Hurler polydystrophy.
AB  - Mannose 6-phosphate is a recognition marker used by many newly made acid
      hydrolases for their transport to lysosomes. Previously, we investigated the
      incorporation of 32Pi into alpha-L-fucosidase of lymphoid cell lines from a
      healthy individual (control) and an I-cell disease patient [DiCioccio and Miller,
      Glycobiology, 1, 595-604 (1991)]. Phosphoserine was found in immunoprecipitable
      alpha-L-fucosidase of both control and I-cell lymphoid cells, but mannose 6
      phosphate was identified only in enzyme of control cells. Extension of this
      investigation to lymphoid cultures of a pseudo-Hurler polydystrophy patient also
      identified only phosphoserine in alpha-L-fucosidase. Using [3H]mannose instead of
      32Pi, the precise identification of mannose 6-phosphate in alpha-L-fucosidase of
      control cells, and its absence in alpha-L-fucosidase of I-cell and pseudo-Hurler
      cells, was established. The stoichiometry of phosphorylation of alpha-L
      fucosidase in I-cell, pseudo-Hurler and control lymphoid cells was 3, 4 and 10
      mol Pi/mol enzyme, respectively. alpha-L-Fucosidase was located in lysosomes
      isolated from control, I-cell and pseudo-Hurler lymphoid cells by subcellular
      fractionation on Percoll density gradients. Both I-cell and pseudo-Hurler
      lymphoid cells displayed normal intralysosomal activity of alpha-L-fucosidase
      despite lack of the mannose 6-phosphate marker. Thus, I-cell and pseudo-Hurler
      lymphoid cells must possess a mannose 6-phosphate-independent mechanism for
      directing alpha-L-fucosidase to lysosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286864
TI  - 22nd Annual meeting of the Society for Complex Carbohydrates. San Juan, Puerto
      Rico, November 17-20, 1993. Abstracts.

PMID- 8286863
TI  - Structural definition of the non-reducing termini of mannose-capped LAM from
      Mycobacterium tuberculosis through selective enzymatic degradation and fast atom
      bombardment-mass spectrometry.
AB  - The application of extracellular arabinases from a Cellulomonas sp. and fast atom
      bombardment-mass spectrometry (FAB-MS) provided new insight into the structure of
      lipoarabinomannan (LAM) of Mycobacterium tuberculosis, a key molecule in the
      pathogenesis and physiology of the tubercle bacillus. Previously, the non
      reducing arabinan ends of LAM from the virulent (Erdman) strain of M.
      tuberculosis were shown to be 'capped' by short (alpha 1-->2)-linked
      mannopyranose (Manp)-containing oligosaccharides, a product called ManLAM. The
      structural relationship between these Manp units and the underlying
      arabinofuranose (Araf)-containing arabinan was examined by digesting ManLAM from
      M.tuberculosis Erdman with the Cellulomonas enzyme, resolving fragments by
      various means and subjecting the derivatized oligoglycosylalditols to FAB-MS. The
      sequences Manp2Araf4, Manp3Araf4 and Manp1-6Araf6 were recognized as the major
      terminal motifs. Upon complete structural definition, all of the Ara6-containing
      products were shown to be based on a 3,5-linked branched Araf unit, whereas those
      containing Ara4 were linear. Minor non-mannosylated terminal arrangements
      containing Ara4-6, branched, linear and cyclical, were also recognized. In
      addition, the mannan 'core' of ManLAM was isolated from enzyme digests and shown
      to contain segments of the phosphatidylinositol anchor and a 'stub' of the
      arabinan side-chain in the form of a 'linker' alpha-Araf-(1-->5)-Araf unit
      attached to C-2, apparently of the penultimate 2,6-linked Manp residue. The
      structural unravelling of this complex molecule further substantiates the case
      for structural and biological similarities to the enterobacterial
      lipopolysaccharides/lipoglycans and other important 'capped' lipooligomers such
      as the lipooligosaccharides of Neisseria species and the lipophosphoglycan of
      Leishmania promastigotes.

PMID- 8286865
TI  - Management of systemic atrioventricular valve regurgitation in infants and
      children.
AB  - Since September 1979, 53 patients have required operation for systemic
      atrioventricular valve regurgitation at Children's Hospital and Health Center of
      San Diego. (Primary repairs of atrioventricular canal defects are excluded from
      this report.) Diagnoses include single ventricle, cardiomyopathy, congenital
      mitral insufficiency , Marfan's disease, rheumatic heart disease, and a history
      of prior repair of atrioventricular canal defect. Ages ranged from 4 months to 19
      years; median age is 5 years. In 31 patients, the atrioventricular valve could be
      repaired. In 24 patients, the valve was replaced (including two patients
      previously repaired). There were four operative deaths, all in the valve
      replacement group: three following valve replacement, and one following emergency
      thrombectomy. Two early failures in the repair group required valve replacement.
      Techniques for repair included leaflet resection, commissural annuloplasty, ring
      annuloplasty, and chordal shortening. Follow-up reveals good-to-excellent status
      in 38 patients. There were seven late deaths: six following valve replacement
      (one death valve related). Current surgical technique permits repair of the
      systemic atrioventricular valve in many infants and children requiring operation
      for regurgitation. The long-term results of valve repair are good to excellent.
      Repair avoids the morbidity and mortality of valve replacement, e.g.,
      anticoagulation, fixed orifice size, and catastrophic mechanical valve
      malfunction.

PMID- 8286866
TI  - Transatrial-transpulmonary repair of atrioventricular septal defect with right
      ventricular outflow tract obstruction.
AB  - Twenty patients had a repair of an atrioventricular septal defect with tetralogy
      of Fallot (n = 13) or double outlet right ventricle (n = 7). Mean age was 3.5
      years. Surgical technique included transatrial-transpulmonary resection of right
      ventricular outflow tract obstruction and transatrial two patch repair of the
      atrioventricular septal defect. Ten patients required a transannular patch and
      one patient had a right ventricle-pulmonary artery conduit placed. There was no
      hospital mortality, and mean hospital stay was 15 days. One patient had late
      sudden death of unknown cause. Six patients have required reoperation because of
      residual ventricular septal defect (VSD), mitral incompetence, residual right
      ventricular outflow tract obstruction, and/or conduit stenosis. No patient was
      reoperated on because of left ventricular outflow tract obstruction. Fifteen
      patients are asymptomatic, one has exertional dyspnea, and two have intermittent
      occasional bronchospasm. The transatrial-transpulmonary two patch repair and
      extensive relief of right ventricular outflow tract obstruction have given good
      immediate results. Reoperation rate has been high mainly due to residual VSD and
      mitral incompetence.

PMID- 8286867
TI  - Intramyocardial dissecting hematoma: an unusual form of subacute cardiac rupture.
AB  - Intramyocardial dissecting hematoma following myocardial infarction is an unusual
      form of subacute cardiac rupture that tends to develop along naturally occurring
      dissection planes between the spiral muscles of the ventricle. The diagnosis has
      commonly been made at surgery, postmortem examination, or by echocardiography.
      Most are associated with acute transmural inferior infarction. Few patients
      survive without surgical intervention. Fourteen cases have appeared in the
      literature. One additional case is described. Ten cases were treated medically
      with one survivor (10%). Five cases were treated surgically with five survivors.
      Surgical treatment of intramyocardial dissecting hematoma is preferable to
      medical treatment. Proper and timely diagnosis and prompt surgical treatment are
      necessary before complete myocardial rupture ensues. Diagnosis is facilitated
      through the use of two-dimensional echocardiography. Successful surgical
      management of this condition requires an appreciation of commonly associated
      pathoanatomical conditions, and the utilization of appropriate methods of repair
      in the presence of potential ventricular septal and ventricular free wall
      rupture.

PMID- 8286868
TI  - Mechanical support for decompression of the left ventricle in repair of ischemic
      cardiac rupture.
AB  - Acute cardiac rupture is often a lethal complication of transmural myocardial
      infarction. A case of successfully treated left ventricular free wall rupture is
      described. Preoperative hemodynamic stabilization was achieved by intraaortic
      balloon counterpulsation. A BioMedicus left ventricular assist device was used
      intraoperatively and postoperatively to obtain long-term intraventricular
      decompression to allow for suture repair of friable myocardium.

PMID- 8286869
TI  - The DiMarco-Jurado pleuropericardioplasties: complete closure of the pericardial
      space with advancement/rotation flaps after adult primary cardiac operations.
AB  - This article describes three new techniques for completely closing the
      pericardial space. They entail the creation of three flaps of living,
      vascularized tissue: two pericardial and one pleural. Utilizing advancement and
      rotational plastic surgical principles, complete closure can be performed without
      tension or the use of any pericardial substitutes. These flaps create great
      laxity and tissue redundancy during closure, greatly reducing any possibility of
      graft compromise or impairment of myocardial diastolic function. There are three
      types of closure described, types I and Ia, and type II, creating great
      versatility in closing the pericardial space (and adaptability to the surgeon's
      preferences). These flaps are able to create pericardial tissue redundancy (and
      therefore laxity upon closure) in both the transverse and longitudinal
      directions, and are therefore suitable to any cardiac procedure. The advantages
      of these techniques in creating a tension-free complete closure include the
      possibility of a safer reoperation if needed. The DiMarco-Jurado
      pleuropericardioplasties as described are quick and easy methods to completely
      close the pericardial space without tension and may be utilized after all adult
      (and possibly pediatric) primary cardiac procedures.

PMID- 8286870
TI  - Protection of the internal mammary artery pedicle with polytetrafluoroethylene
      membrane.
AB  - With increasing frequency, reoperative coronary artery bypass surgery is being
      performed in the setting of a patent internal mammary artery (IMA) graft. Injury
      to the IMA graft at reoperation can result in ischemic myocardial injury and
      cardiac arrest. This descriptive laboratory study examined use of a
      polytetrafluoroethylene (PTFE) membrane wrap to protect the IMA pedicle during
      sternal reentry. Six pigs (25-30 kg) underwent median sternotomy and takedown of
      left and right IMAs. Grafts were implanted in the epicardium by a modified
      Vineberg procedure. In each animal, one IMA was wrapped circumferentially with
      PTFE, while the contralateral bare IMA served as the control. Redo sternotomy was
      performed 3 months later. Severe adhesions between chest wall, myocardium, and
      bare IMA grafts were encountered in six of six animals. PTFE-wrapped IMAs were
      easily identified by appearance and by palpation. There was no adherence between
      PTFE membranes and surrounding tissue, nor was there evidence of cellular
      infiltration, disruption, or contraction of the membrane. Most notably, PTFE
      membranes could not be cut or injured with the electrocautery, since they are
      electrical nonconductors. This study demonstrates that PTFE membrane: (1) is
      relatively inert and incites minimal surrounding tissue reaction; and (2) is
      impenetrable to electrocautery injury. Further studies are necessary to determine
      the impact of PTFE membrane on IMA graft patency and wound infection. PTFE
      membrane may prove clinically useful in protecting patent IMA pedicles during
      reoperative cardiac surgery.

PMID- 8286871
TI  - In vitro cultivation and immunogenicity of human cardiac valve endothelium.
AB  - Endothelial cells were derived from aortic and mitral valves (n = 17) by
      collagenase digestion and subsequently cultivated in RPMI medium supplemented
      with 20% fetal calf serum. The cells were stained in an alkaline phosphatase-anti
      alkaline phosphatase stain for the expression of MHC Class I and Class II
      antigens, ICAM-1, ELAM-1, F VIII, and H/Y. The endothelium showed a strong
      expression of Class I, H/Y, and ICAM-1 molecules, and weak expression of MHC
      Class II molecules. In contrast to vascular endothelium that is known to express
      F VIII constitutively, cardiac valve endothelium was found to be negative. F VIII
      and ELAM-1 were only expressed after stimulation with recombinant interferon
      gamma. To analyze the immunogenicity of valve endothelium, cells were used as
      stimulator cells in a mixed cell culture reaction using lymphocytes as responder
      cells. Endothelial cells had a 2 to 3 times higher stimulatory effect than
      peripheral blood lymphocytes. These data allow speculation on whether the
      observed degeneration of homografts can be reduced if HLA matching is performed
      prior to valve implantation.

PMID- 8286872
TI  - Semilunar valve replacement with a cylindrical valve.
AB  - A cylindrical valve was designed to prevent regurgitation of the semilunar valve.
      The valve is made of a sheet of polytetrafluoroethylene (PTFE) or porcine
      pericardium, and has three cusps and three commissures. The diameter of the valve
      is equal to the height of the cusps. We have used these valves in pulmonary
      stenosis after Jatene's operation and total correction of tetralogy of Fallot,
      and for truncal valve regurgitation. Regurgitation was trivial on color Doppler
      echocardiography in all cases. Advantages in comparison with the implantation of
      commercially available artificial valves include the ability to insert a larger
      size and no compression of the valve ring when closing the sternum. Outflow tract
      obstruction does not occur even when the valve is implanted in a small infant. In
      the present report, we describe this simple technique.

PMID- 8286873
TI  - Wound complications and treatment of the infected implantable cardioverter
      defibrillator generator.
AB  - Since 1980, the automatic implantable cardioverter defibrillator (ICD) has
      evolved as effective therapy for prevention of sudden cardiac death following
      documented sustained ventricular tachycardia or fibrillation. During a 5-year
      period, 412 ICD devices were implanted at the University of Michigan Hospitals
      with a wound complication rate of 4.1%. In this group, there were 13 infections,
      3 erosions of the generator pocket, and 1 wound hematoma. Of the 16 patients with
      infection or erosion, 12 patients were treated with a rectus abdominis muscle
      flap closure and 4 with ICD generator removal. In 83% (n = 12) of the muscle flap
      patients, the wound healed uneventfully. Preoperative chest CT scanning was found
      to be helpful in identifying probable infection of the epicardial leads. In these
      cases, all hardware had to be removed to achieve resolution of the infection. We
      concluded that rectus abdominis muscle flaps were helpful in salvaging infected
      or exposed ICD generators in the absence of infected epicardial leads.

PMID- 8286874
TI  - Intraoperative echocardiography: techniques and current applications.
AB  - Intraoperative echocardiography has opened new dimensions in the evaluation of
      cardiac surgical patients, and has contributed significantly to the improved
      surgical results. The use of intraoperative echocardiography has enabled the
      surgeon to image the working heart, to define the operative anatomy and
      physiology, and to evaluate the results immediately before the patients leave the
      operating room. This review summarizes the current status and applications of
      intraoperative echocardiography in the practice of cardiac surgery.

PMID- 8286875
TI  - An alternative technique for cardiac transplantation.

PMID- 8286876
TI  - Aortic valve replacement and mitral valve repair with allograft.

PMID- 8286877
TI  - Experimental evidence for and clinical implications of fiber and artificial
      enteral nutrition.

PMID- 8286878
TI  - Differential effects of sepsis and trauma on urinary excretion of polyamines.
AB  - Urinary excretion of polyamines increases in patients with trauma and infection.
      To separate the effect of infection from the general metabolic response to
      sepsis, we studied 7 patients with sepsis and 13 patients with multiple trauma in
      the intensive-care unit. Urinary excretion of total and free polyamines,
      putrescine, spermidine, spermine, and their metabolites N1-acetylspermidine (N1
      AcSPD) and N8-acetylspermidine (N8-AcSPD), and energy and nitrogen balance were
      measured. The patients were randomized to receive either hypocaloric glucose
      alone or with amino acids for 2 days. The excretion of individual polyamines,
      except spermine, significantly exceeded normal values in both patient groups; the
      excretion of total polyamines was 530 and 323% higher than normal in patients
      with sepsis and trauma, respectively. The excretion of N1-AcSPD and total
      spermidine was 141 and 74% higher in patients with sepsis than in patients with
      trauma, respectively (p < 0.05), whereas the excretion of N8-AcSPD was equal in
      both patient groups. This was also reflected as a significantly increased urinary
      ratio of N1-AcSPD to N8-AcSPD in septic patients (6.37 +/- 1.61; mean +/- SE)
      compared with patients after injury (2.69 +/- 0.27, p < 0.01) or a healthy
      population (1.08 +/- 0.04, p < 0.001). Amino acid infusion had no effect on
      polyamine excretion. The mean energy balance was -17.0 +/- 1.1 and -19.1 +/- 1.1
      kcal.kg-1.day-1, and the mean nitrogen balance was -0.17 +/- 0.03 and -0.15 +/-
      0.02 g.kg-1.day-1 in patients with sepsis and trauma, respectively (NS).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8286879
TI  - Nutrition status, severity of illness, and thermogenic response to parenteral
      nutrition.
AB  - The effect of the degree of metabolic stress on the thermogenic response to
      parenteral nutrition was studied in surgical and intensive-care patients.
      Indirect calorimetry was measured before and 3 h after the start of parenteral
      nutrition. The following patient groups were studied: depleted ward patients
      before and after surgery for gastrointestinal malignancy (n = 16), mechanically
      ventilated sepsis/injury patients (n = 21), and spontaneously breathing intensive
      care sepsis/injury patients (n = 8). The patients received either nonprotein
      energy alone (glucose/fat 30/70%) at a rate corresponding to 1.4-1.6x baseline
      resting energy expenditure (REE) or amino acids (1.5 g.kg-1.day-1) and
      hypocaloric glucose. There was no correlation between the thermogenic effect of
      nutrition and the degree of hypermetabolism or degree of malnutrition. There was
      no significant thermogenic response to either amino acids or hypercaloric lipids
      and glucose preoperatively. In the depleted patients, REE increased because of
      the operation (p < 0.05); postoperatively, only amino acids increased REE
      significantly (p < 0.05). The operation enhanced the thermogenic response, which
      was higher to amino acids than to nonprotein energy (27.2 +/- 9 vs. 5.3 +/- 2.2%,
      means +/- SE, p < 0.05). In the sepsis/trauma patients, REE increased in both
      nutrition groups (p < 0.05). The thermogenic response (19.7 +/- 6.5 and 8.0 +/-
      3.2% in patients receiving amino acids and nonprotein energy, respectively) was
      similar to that of the depleted patients postoperatively and was similar in
      sepsis and trauma patients. We conclude that the thermogenic response to
      parenteral amino acids and nonprotein energy is minor in depleted
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286880
TI  - Changes in iron status during competitive season in female collegiate swimmers.
AB  - We examined changes in iron status in 25 female varsity collegiate swimmers over
      the course of a competitive season via weekly capillary blood sampling. We also
      studied the effectiveness of moderate iron supplementation (39 mg/day) in
      preventing expected changes in iron status via a double-blinded crossover design.
      On entry into the study, 17 of the swimmers had depleted iron stores (plasma
      ferritin < 12 micrograms/L) and 5 were anemic (Hb < 120 g/L). After 5 wk of
      placebo treatment, hemoglobin decreased (> or = 6 g/L) in 44% and increased in
      12% of the subjects. After 5 wk of iron supplementation, hemoglobin decreased in
      16% and increased in 24% of the subjects. Likewise, after placebo treatment,
      plasma ferritin decreased (> or = 5 micrograms/L) in 24% and increased in 4% of
      the subjects, whereas iron supplementation resulted in decreases in 4% and
      increases in 68% of the subjects. In the absence of iron supplementation,
      hemoglobin levels decreased despite mean dietary iron intakes of 16.3 mg/day.
      These results show that moderate iron supplementation is effective in preventing
      decline in the iron status of female collegiate swimmers during a competitive
      season, but a higher dose of iron may be necessary to reverse their iron
      deficient state.

PMID- 8286881
TI  - Response of individual serum free fatty acids to oral and intravenous glucose:
      relation to adipose tissue composition.
AB  - The rate of oral glucose delivery determines whether serum total free fatty acids
      remain low (glucose sipping over 210 min) or rebound 120-180 min after initial
      suppression (via glucose bolus), but the response of individual serum free fatty
      acids to glucose ingestion is largely unknown. In this study, we measured the
      changes over 240 min in the levels of individual serum free and esterified fatty
      acids after bolus or sipped glucose ingestion and determined the extent to which
      the changes are related to abdominal subcutaneous adipose tissue composition. In
      eight healthy volunteers, 74% of the prolonged suppression of total serum free
      fatty acids resulting from sipping 50 g glucose over 210 min was caused by a
      decrease in free linoleic and oleic acids, whereas 92% of the rebound in total
      free fatty acids 240 min after consuming 50 g of glucose as a bolus was caused by
      increases in free oleic and linoleic acids. Two hundred forty minutes after the
      oral glucose, slower intravenous clearance of 5 g glucose was directly correlated
      to higher total serum free fatty acids and free stearic acid and higher oleic but
      lower linoleic acid in adipose tissue. We conclude that the net response of serum
      free fatty acids to an oral glucose load is mediated primarily by oleic and
      linoleic acids in a manner largely unrelated to adipose tissue composition.

PMID- 8286882
TI  - Liver reserves of iron, copper, and vitamin B12 in Brazilian fetuses and infants
      of different socioeconomic status.
AB  - The purpose of this study was to investigate the influence of the stage of fetal
      development and of maternal socioeconomic status on liver concentrations and
      total liver reserves of iron, copper, and vitamin B12 in Brazilian fetuses and
      infants. Eighty fetuses and infants ranging from 19 to 42 wk of gestational age
      were studied. Liver concentrations of nutrients did not vary significantly with
      the stage of fetal development. Therefore, increases in total liver reserves
      during development were caused mainly by increases in liver weight. There were
      significant correlations between total liver reserves of vitamin B12 and iron (r
      = 0.742, p < 0.001), vitamin B12 and copper (r = 0.444, p < 0.001), and iron and
      copper (r = 0.431, p < 0.001). Maternal socioeconomic status did not affect liver
      nutrient concentrations or total hepatic levels at any stage of fetal
      development.

PMID- 8286883
TI  - Metabolic rate and nitrogen balance after skeletal trauma in female and male
      rats.
AB  - Unequal metabolic responses to trauma by women and men have been suggested, but
      an explicit investigation demonstrating this conjecture has not been made. The
      responses of resting energy expenditure (REE) and nitrogen balance for 3 days
      before and 7 days after skeletal trauma were determined for female and male rats.
      Food intake and body weight were recorded daily, and 24-h urine samples were
      collected. Baseline REE and nitrogen balance were obtained for 3 consecutive days
      before induction of trauma. Then rats were divided into female trauma (n = 8),
      male trauma (n = 7), female control (n = 8), and male control (n = 7) groups.
      Trauma was produced by bilateral femoral fracture to anesthetized rats. Control
      rats were anesthetized without skeletal trauma. Traumatized rats were fed ad
      libitum for 7 days, and control rats were pair fed with the traumatized rats. The
      results showed that REE increased and nitrogen balance decreased in traumatized
      male rats relative to their controls. Traumatized female rats had increased REE
      and unchanged nitrogen balance compared with their controls. Traumatized female
      rats had a larger percentage increase in REE on days 5 through 7 than did
      traumatized male rats. These findings demonstrate a difference between female and
      male rats in response to trauma. Female rats use more energy and lose less
      nitrogen after trauma than do male rats. The results suggest that recommendations
      for increased energy and protein needs after trauma should consider the sex of
      the subject intended to be fed.

PMID- 8286884
TI  - Densitometry-based equations for estimating body composition in Fischer rats.
AB  - Male Fischer rats are widely used to evaluate the effects of nutritional
      repletion or deprivation on the rat's nutritional status. Practical methods are
      needed to evaluate changes in body composition. Chemical analysis is expensive,
      time consuming, and often not available; bioelectrical impedance analysis in
      laboratory animals lacks standardization. Postulating that the measurement of
      densitometry would allow reliable estimation of body composition in the male
      Fischer rat, we studied 27 male Fischer rats. Densitometric measurements of the
      carcasses and their chemical analysis were performed to obtain reference values.
      Initial estimation of the fraction of body fat based on densitometry was
      attempted with the Siri equation intended for use in humans. We found that this
      equation was not suitable for use in the male Fischer rat because it
      underestimated fat mass at high carcass weights and overestimated fat mass at low
      carcass weights. Therefore, the Siri equation was modified to more accurately
      predict carcass composition in the male Fischer rat. Three different predictive
      equations based on simple densitometric measurements were developed that allow
      separate estimation of carcass fat, carcass water, and carcass protein in the
      male Fischer rat. These equations were found to be accurate to within 2-5-3% of
      carcass weight.

PMID- 8286885
TI  - Total parenteral nutrition in pregnant patient with hyperemesis gravidarum.

PMID- 8286886
TI  - Abdominal obesity as important component of insulin-resistance syndrome.
AB  - The regional distribution of body fat has been identified as a significant risk
      factor for the development of noninsulin-dependent diabetes mellitus and
      cardiovascular disease (CVD). Several studies that have investigated the
      potential associations between topographic features of adipose tissue and indices
      reflecting carbohydrate and lipid metabolism have reported significant
      associations between abdominal fat deposition and metabolic complications. The
      development of computed tomography as a means to precisely measure the amount of
      subcutaneous and deep adipose tissue at any site of the body has shown that
      determination of the level of visceral adipose tissue is a critical measurement
      to perform in the assessment of the health hazards of obesity. Studies that we
      have conducted in premenopausal women have clearly shown that the level of
      visceral adipose tissue is the best correlate of lipoprotein ratios used to
      estimate the risk of CVD. We have also reported that a high level of visceral
      adipose tissue is associated with a deterioration of glucose tolerance and that
      the relationship between visceral fat deposition and glucose tolerance remains
      significant after controlling for the level of total-body fat. Because
      significant interrelationships were observed between abdominal visceral obesity,
      insulin resistance, and dyslipoproteinemias in obese women, it is suggested that
      visceral obesity is an important component of the insulin-resistance syndrome
      (syndrome X) that has been previously described. This cluster of morphological,
      hormonal, and metabolic alterations observed in abdominal obesity may have
      substantial implications for the treatment of this condition.

PMID- 8286887
TI  - Protein quality, amino acid balance, utilization, and evaluation of diets
      containing amino acids as therapeutic agents.
AB  - Basic concepts of amino acid nutrition are summarized and quantitative amino acid
      requirements of different age-groups based on current knowledge are presented.
      The newer concepts of "conditionally indispensable" amino acids and organ
      specific requirements for amino acids are discussed. The concepts of nitrogen
      balance, limiting amino acid, protein utilization, protein efficiency ratio, and
      amino acid score for determining protein quality are reviewed, and examples of
      low-, intermediate-, and high-quality proteins are provided. Problems in
      assessing efficiency of nitrogen utilization when single amino acids or amino
      acids in combination with balanced diets are used as therapeutic agents are
      discussed in relation to the potential roles of the branched-chain amino acids,
      arginine, and glutamine in trauma and as immunostimulators.

PMID- 8286889
TI  - Aims and objectives of societies of parenteral and enteral nutrition.

PMID- 8286888
TI  - Measurement of total-body fat by underwater weighing: new insights and uses for
      old method.

PMID- 8286890
TI  - Clinton health-care reform ... the inside track.

PMID- 8286891
TI  - Nonparametric tests of hypothesis.

PMID- 8286892
TI  - Little common ground seen in proposed U.S. laws vs. regulations on dietary
      supplements.

PMID- 8286893
TI  - Body composition from fluid spaces and density: analysis of methods. 1961.

PMID- 8286894
TI  - [Quality management in the hospital--methodological comments on quality effects
      of two aspects of a real case].
AB  - In this article two aspects of a clinical case, known in Germany as the Marion P.
      case, are adapted to fit into Donabedians systematic of factors of influence on
      health care quality. These aspects, case-related communication between doctors on
      the one hand and between doctors and directly affected persons on the other, are
      also viewed as specific problems of decision making. It turns out that in either
      situation the probability theory based medical decision analysis could have been
      an important contribution to improve problem transparency, i.e. medical decision
      analysis could have been used as a tool for quality management in hospitals.

PMID- 8286895
TI  - [Patients of private practice physicians--selected results of a survey in general
      practice offices].
AB  - The structural changes in outpatient medical care in the new Federal Laender were
      characterised by the fact that doctors now established their own medical practice
      whereas previously they had been part of a state-controlled and state-organised
      system of medical centres for outpatient treatment. The aim of the present study
      consisted in analysing the opinions of patients on these changes in ambulatory
      medical care from state control to a physician in own medical practice. The
      standardised questionnaire used in this study contained questions on the
      conditions of organisation within the practice, e.g. waiting period, consultation
      period, home visit and accessibility of the doctor. Furthermore the patients were
      asked for important criteria of medical care by a family doctor. Selected results
      of this inquiry of patients are compared to a study realised in 1988/89 under
      conditions of the former public health system of the GDR. Comparison of both
      studies results in significant differences. In a practice of a consulting-room
      practitioner the waiting period is shorter, the accessibility of the doctor is
      better and the time of consultations is positively changed compared to the former
      public health system. In 1992 about 94% of patients considered the general
      practitioner in his own practice as their family doctor, in 1988/89 under the
      conditions of the public health system only 66% of patients did so. These
      differences are due to the higher degree of realisation of the criteria of
      medical care by a family doctor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286896
TI  - [Comparative clinical, microbiologic and serologic studies of the incidence of
      genital and para-genital infections in prostitutes and women with mainly
      monogamous relations].
AB  - Legislation of the control of sexually transmitted diseases (STD) in the Federal
      Republic of Germany covers neither the complete spectrum of venereal diseases nor
      all population groups of high risk. We therefore investigated not only the
      classic STD but also some other STD, i.e. by serologic methods syphilis, HIV
      infection, hepatitis A, B, C, and herpes simplex genitalis, and by
      microbiological methods gonococci, chlamydiae, trichomonas, genital mycoplasmas,
      A-streptococci, B-streptococci, gram-negative enteric bacteria, anaerobic
      bacteria, staphylococci, listerias and yeasts. The cohorts of women living mainly
      monogamously and these of prostitutes were compared. They show some differences:
      There are remarkable differences in the prevalence of clinical symptoms, i.e.
      vaginal discharge, rubor, pruritus, and genital warts, between the two cohorts
      and depending on the season. Fluor, rubor, and pruritus were more frequently
      observed in mainly monogamous women than in prostitutes. Furthermore, the
      causative organisms of STD were isolated in different frequencies depending on
      the season particularly from mainly monogamous women. Furthermore, their
      frequencies depend on the age of the women. Gonococci, chlamydiae, trichomonas,
      genital mycoplasmas, B-streptococci and Staphylococcus aureus were significantly
      more isolated from prostitutes than from mainly monogamous women. But, on the
      other hand, candida and gram-negative enterobacteria are significantly more
      common in mainly monogamous women than in prostitutes. There are some
      correlations between clinical symptoms and organisms. The prevalence of syphilis,
      HIV-infection, hepatitis A, B, and C in the prostitutes were 7, 0.4, 3.5, 15, and
      1.6%, respectively. The most intriguing observation is the decreasing incidence
      of causative organisms of STD in prostitutes during the three years of study.
      This phenomenon promises an improvement of the health standard of prostitutes by
      regular medical, microbiological, serological check-ups without charge.

PMID- 8286897
TI  - [PCB caulking sealants--experiences and results of measures in Berlin and
      decontamination of a school (Part I)].
AB  - PCB contamination of indoor air in public buildings by elastic sealants has
      proved to be a serious problem in West Berlin. Besides a general survey and
      introduction into the toxicological problem the procedure and experiences in
      Berlin are presented. Besides a proposal of a catalogue of several preventive
      measures, sampling and analytical methods are also described. During the control
      of about 220 buildings, 40 turned out to be PCB-contaminated, mostly gymnastic
      halls (30). In former East Berlin no PCB contamination by elastic sealants is
      known so far. In part 2 experiences and results of a restoration of a school
      building are reported.

PMID- 8286898
TI  - [Health education in developing countries--Indian health promoters in a
      tuberculosis prevention program in the Chaco region of Paraguay].
AB  - Several characteristics obstacles exist in developing countries in respect of
      implementation or realisation of health programmes. The following article,
      however, shows how effective preventive health and health care measures can be
      made possible even in the face of seemingly insurmountable difficulties. The only
      presently existing model basing on many years of experience, consequent
      development and documented success in the targeted prophylaxis of tuberculosis,
      is that of the Latin American Indian health promoters in the Chaco of Paraguay.
      The article discusses the results of the authors' own investigations regarding
      the training curriculum for the job of a "health promoter", delegation and
      distribution of tasks and success of the programme (incidence of tuberculosis and
      death rates). These are discussed in respect of general consequences for a
      concept of health training in developing countries.

PMID- 8286899
TI  - [Tolerance of preventive influenza vaccination with a subunit vaccine].
AB  - The frequency and intensity of undesirable side effects after protective
      vaccination against influenza with a commercially available vaccine were studied.
      82 gainfully employed persons of both sexes were questioned in respect of local
      reactions such as weal and flare reactions, itching, sensation of heat,
      tenderness on pressure, and impeded movement, as well as systemic reactions e.g.
      elevated temperature or fever, profound sweating, headache, malaise, and
      insomnia. In 61 of 82 questioned persons local reactions occurred within 24 hours
      after vaccination, mainly weal and flare reactions and tenderness on pressure. 10
      persons had systemic reactions, chiefly headache and fever, 39 of the questioned
      persons who reported on undesirable effects considered these impairments to be
      slight, whereas 28 of the group did not feel that the impairments disturbed or
      upset them in any way.

PMID- 8286900
TI  - [Public health measures in homes for the aged and nursing homes].
AB  - It was the purpose of this study to give a survey of standards of hygiene in
      homes for the aged as well as nursing homes and to find out whether there is any
      need of appropriate training measures. Furthermore, we tried to compile a brief
      standard of assessment that should enable public health officers to draw up a
      standardised documentation of inspections. Four homes of the aged or nursing
      homes were chosen. At a cursory inspection two of them seemed properly run,
      whereas the other two showed certain deficiencies. Using a questionnaire that
      covered 11 fields of interest each home was registered 5-fold at intervals of 6
      weeks and once again 22 months later. 3 training courses were held at one home of
      each type (properly run, less properly run). Urine analyses served as indicators
      for the success of these courses. The most important and relevant points of each
      field of hygiene were chosen to compile a short schedule of assessment. By means
      of the detailed questionnaire it was possible to register completely the standard
      of hygiene and to check on the nursing of the patient. Inspections alone improved
      the standards of hygiene of those homes where no training courses had been held
      (homes B and C). With the other two homes the attitude towards hygiene improved
      even if the staff was less motivated (less properly run home D, trained). When
      the regular inspection and training measures had been interrupted for a longer
      time, the standards of hygiene were maintained only partially in some areas of
      interest.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286901
TI  - [Dreams in the elderly: contents and clinical usefulness].
AB  - This article reviews the literature on the dreams of persons beyond 50 years of
      age. A reduced dream recall rate, if at all, does not appear to be the result of
      weakened memory capacities at that age, but may rather be due to a lower rate of
      current concerns. In a similar way, the changes in contents are not a function of
      aging per se, but have taken place already between the 20th and 45th year of age.
      The dreams of the dying can, because of the unusualness of the situation
      experienced by this group, be of a very particular nature and quality. At any age
      of life, the dream can become instrumental in healing processes. Dreams seem to
      be of vital importance in supportive psychotherapy after bereavement and, of
      course, during the process of dying.

PMID- 8286902
TI  - [Competence to stand trial, capacity to law suits, fitness for imprisonment].
AB  - Frequently, the legal capacity of a person and fitness to be remanded to custody
      have to be examined by a medicolegal expert. Differences exist between legal
      capacity in criminal cases (competency to stand trial) and civil cases (capacity
      to sue and to be sued). Hence, a review is given for conducting practical work in
      the medicolegal field.

PMID- 8286903
TI  - [The nursing care insurance law].
AB  - By establishing an independent statutory nursing care insurance, the security of
      patients in need of nursing care and the organisation of nursing care will be
      placed on a new basis. For instance, the bill provides for substantially extended
      benefits for home care and also includes benefits for long-term care in nursing
      homes into the general risk pool. The nursing care funds yet to be founded will
      receive the service guarantee for the organisation of nursing care, negotiate
      contracts with the respective nursing institutions and monitor their quality.
      Although the envisaged range of benefits covered by the statutory nursing care
      insurance has been noticeably extended it remains doubtful whether these benefits
      will be sufficient or whether there will still be the need for supplemental
      income support payments for nursing care. Moreover, the set of tools for
      regulation remains contradictory as the regulating competences of the Federal
      Government and those of the nursing care funds overlap. The Medical Service of
      the Statutory Health Insurance will be given extended responsibilities regarding
      the examination of individual cases, including the determination of the degree of
      a patient's need for nursing care, checking the possibility of rehabilitation and
      giving advice for individual care. Apart from that, it will assume new duties in
      the fields of quality assurance of the nursing care institutions and consulting
      the nursing care funds.

PMID- 8286904
TI  - [The guardianship law and physician's responsibility].
AB  - From 1992 a new law regulating the taking care of another person's legal and
      personal affairs and nursing problems has become effective. The aim of this law
      is to establish an individual and respectful relationship between the patient in
      care and the appointed person. The appointed person has to emphathize with the
      patient in his care to a degree where he is able to make decisions that reflect
      the individual lifestyle and life history of the patient in care. Fundamentally,
      it is the patient's right to make his own decisions about medical treatment
      according to tis own experience, personal values and emotions. If the patient is
      unable to make his own decisions for health reasons a caretaking person is
      appointed by decree. In respecting the patient's will stringent standards are
      necessary. The new law offers possibilities of freedom of decision and self
      responsibility that should never be restricted again.

PMID- 8286905
TI  - [Comments on the report "Reform of public health in the new German lands" by F.
      Beske].

PMID- 8286906
TI  - A review for school nursing professionals: adolescent depression.
AB  - Adolescent depression occurs within various developmental, social, and biologic
      contexts, and is manifested by traditional depressive symptoms such as fatigue,
      loss of interest in daily activities, weight changes, sleep disturbances, sad
      moods, difficulty with concentration, behavioral agitation or lethargy, feelings
      of worthlessness, and recurrent thoughts of death. Depressed adolescents may
      combine these symptoms with certain additional behaviors such as academic
      deterioration, substance abuse, sexual activity, somatic complaints, eating
      disorders, conduct disorders, and other risk-taking behaviors. School nurses can
      play a central role in the prevention, assessment, referral, and follow-up care
      of this significant adolescent health problem.

PMID- 8286907
TI  - Caring for the child with Down syndrome.
AB  - This article reviews the etiology, treatment, and prognosis of Down syndrome.
      Effects of Down syndrome on growth and development, specific physiologic
      manifestations, and implications for school-based practice are discussed.

PMID- 8286908
TI  - Nursing practice management: Susan D. is a 3-year-old female who was diagnosed at
      birth with Down syndrome.

PMID- 8286910
TI  - Leadership.

PMID- 8286909
TI  - School nurses' perceptions of the health needs of Hispanic elementary school
      children.
AB  - School nurses' perceptions of the health needs of Hispanic elementary school
      children were surveyed in a national sample. Differences among the identified
      priority health needs were found for Hispanic subgroups and states of residence.
      Possible implications for school health personnel are discussed.

PMID- 8286911
TI  - Anaphylaxis at school.
AB  - Anaphylaxis is a life-threatening allergic reaction. It can occur after insect
      stings or food intake in susceptible children and adolescents while at school.
      The respiratory, cutaneous, gastrointestinal, and cardiovascular systems are
      often affected, and prompt treatment with injected epinephrine may be life
      saving. It is important for school nurses to be familiar with the early
      recognition, prompt treatment, and prevention of anaphylaxis.

PMID- 8286912
TI  - The contribution of secure hospitals to social control.

PMID- 8286913
TI  - APL: some international perspectives.

PMID- 8286914
TI  - Therapeutic use of reminiscence with the elderly.
AB  - Reminiscence may often be undervalued as a therapeutic activity. This article
      highlights the therapeutic potential of reminiscence and the important issues
      that need consideration for its effective use with elderly people suffering from
      dementia.

PMID- 8286915
TI  - An outline of the forensic nursing role.
AB  - Nurses working within secure institutions are agents for both therapy and
      custody. With its distinctive client group, predominantly institution-based care,
      exceptional knowledge base and clinical focus on mental disorder and deviance,
      forensic nursing can justifiably claim the status of a specialty.

PMID- 8286916
TI  - Psychosocial impact of end-stage renal disease.
AB  - Renal dysfunction has a profound physical, psychological, social and sexual
      impact. The impact of end-stage renal disease can be interpreted in terms of
      crisis theory and interventions planned. Factors predicting non-adherence to
      therapy can be isolated and managed in order to promote adherence. The challenge
      of renal disease can be met by a collaborative multidisciplinary approach.

PMID- 8286917
TI  - The group that cares for carers.
AB  - In response to two surveys of carers a carers group was set up at the Day
      Hospital of Wharfedale General Hospital. It aims not only to provide emotional
      support to empower elderly patients and their carers but also to supply a means
      of communication with professionals.

PMID- 8286918
TI  - Role of the nurse teacher as researcher.
AB  - Nurse teachers have an important role to play in nursing research. This article
      examines this role and considers some of the factors that prevent nurse teachers
      from increasing their research activity. It also highlights methods by which
      nurse teachers and nursing practitioners can work together to reduce the
      theory/practice gap and improve patient care.

PMID- 8286919
TI  - A personal view of asthma.

PMID- 8286920
TI  - Understanding ethics in nursing practice.
AB  - Ethics has traditionally been viewed as an abstract subject confined to the ivory
      towers of academia. This article challenges that view and describes how ethics
      can offer nurses a framework for analysing difficult situations at the interface
      of practice.

PMID- 8286921
TI  - Nurse-aid management of ear and nose emergencies: 2.
AB  - There are many disorders that affect the nose and interfere with its normal
      functioning. This article, the second in a two-part series, examines the common
      disorders and outlines the nurse-aid management.

PMID- 8286922
TI  - Implementing individual performance review.
AB  - This article examines the implementation of individual performance review as an
      effective managerial process for integrating the needs of all nursing staff with
      the needs of the organization. This will ultimately improve the standard of care
      received by patients within the NHS.

PMID- 8286923
TI  - Nurses and pharmacology.

PMID- 8286924
TI  - As nature intended? The uptake of DNA and oligonucleotides by eukaryotic cells.

PMID- 8286925
TI  - An overview of computer software developed to search biological sequence
      databases.
AB  - The scientific community has established a number of databases to receive and
      maintain the abundant biological sequence information being generated by research
      investigators worldwide. For researchers in an increasing number of biological
      disciplines, the information stored in these databases has become an invaluable
      tool in their daily research endeavors. This article reviews the organization of
      the largest nucleic acid and protein sequence databases and discusses some of the
      commonly available computer software that has been developed for searching them.

PMID- 8286926
TI  - A ribozyme that enhances gene suppression in tobacco protoplasts.
AB  - Site-directed mutagenesis has been used to produce two hammerhead ribozyme
      molecules targeting the chloramphenicol acetyltransferase gene (CAT). One
      ribozyme has a single catalytic domain between two 12-nucleotide arms that can
      hybridize 5' and 3' of the GUC target site of the CAT RNA transcript. The second
      ribozyme is a full-length antisense RNA with four catalytic domains inserted
      along the length, each targeting a specific GUC site within the CAT mRNA. Our
      results show that both ribozymes can produce almost equivalent rates of cleavage
      of the CAT mRNA in vitro (T1/2 of 18 or 15 min, respectively). In tobacco
      protoplasts we show consistently greater gene suppression in the presence of the
      long ribozyme molecule, compared with the equivalent antisense (22% gene
      reduction for antisense compared with 44% with the long ribozyme). These results
      suggest that hammerhead ribozymes may be developed for the inactivation of gene
      activity in plant cells.

PMID- 8286927
TI  - Oligonucleotide-poly-L-ornithine conjugates: binding to complementary DNA and
      RNA.
AB  - On the basis of the reported enhanced antisense activity of polylysine
      oligonucleotide conjugates, a synthetic 12-mer oligodeoxyribonucleotide has been
      coupled at its 5' terminus to a series of positively charged (delta-ornithine)n
      cysteine peptides. Binding between the nucleic acid-peptide conjugate and its
      complementary DNA target sequence was detected by the impact of complexation on
      the melting temperature (Tm). It was found that the Tm for the nucleic acid
      peptide gradually increased with increasing net charge on the conjugated peptide.
      Site-directed cleavage with RNase H demonstrates that the peptide-modified
      oligomer also hybridizes with its RNA target sequence. Increased affinity for
      target mRNA with net charge was shown by a cell-free translation arrest assay.

PMID- 8286928
TI  - Pharmacokinetics, biodistribution, and stability of capped oligodeoxynucleotide
      phosphorothioates in mice.
AB  - Several end-modified oligodeoxynucleotide phosphorothioates (S-oligonucleotides)
      were studied for their pharmacokinetics, biodistribution, excretion, and
      metabolic stability in vivo after intravenous administration in mice. The overall
      tissue distribution and excretion patterns of these S-oligonucleotides were found
      to be independent of 5' or 3' end modification studied. However, the 3' end
      modification proved to be of considerable importance with respect to metabolic
      stability of the oligonucleotide. In the case of uncapped and 5'-capped S
      oligonucleotide, only 50% of intact oligonucleotide was recovered out of the
      total bioavailable concentration in liver and kidney. In contrast, in the case of
      3'-capped oligonucleotides almost all bioavailable concentrations of 3'-capped
      oligonucleotide was found to be intact in kidney and liver at 24 hr after
      administration. These results demonstrate that superior pharmaceutical potential
      can be created by 3'-end modification of oligonucleotide phosphorothioates.

PMID- 8286929
TI  - Investigations of oligodeoxyinosine for triple helix formation.
AB  - The ability of a 17-mer of deoxyinosine to form a triple helix with a
      (dT)17(dA)17 segment of a 29-mer Watson-Crick duplex was investigated. Under
      conditions amenable to triple helix formation, (dT)17 showed evidence of complex
      formation as evidenced by UV melting curves and gel mobility shift assays whereas
      (dI)17 did not.

PMID- 8286930
TI  - Single-stranded phosphodiester and phosphorothioate oligonucleotides bind
      actinomycin D and interfere with tumor necrosis factor-induced lysis in the L929
      cytotoxicity assay.
AB  - Antisense oligonucleotides may prove useful tools to elucidate the biological
      functions of cytokines and to address regulatory control of cytokine expression.
      The functional activity of cytokines generally is determined by biological
      assays, and a standard biological assay for TNF activity measures the cytotoxic
      effect of TNF on actinomycin D-sensitized L929 cells (Matthews and Neale, 1987).
      We observed that phosphorothioate and phosphodiester oligonucleotides, at
      concentrations > 100 nM in supernatants tested in this bioassay, prevented TNF
      induced lysis of L929 cells. This "protective" effect was due to an interaction
      of the single-stranded oligonucleotides with actinomycin D as demonstrated by UV
      spectra of an actinomycin D-oligonucleotide solution. Substitution of
      cycloheximide for actinomycin D in the L929 assay eliminated the protective
      effect of the oligonucleotide. Our results reinforce the importance of
      controlling for nonspecific effects of oligonucleotides, particularly when a
      functional assay for protein activity is used to screen for antisense-mediated
      reductions in target protein expression.

PMID- 8286931
TI  - Commentary: regulatory issues affecting oligonucleotides.

PMID- 8286932
TI  - Is the Na(+)-K(+)-ATPase the link between phosphoinositide metabolism and bipolar
      disorder?
AB  - Recent experimental work suggests involvement of the phosphatidyl inositol second
      messenger system in the biochemical mechanism of lithium action, but this work
      has not shed light on the pathophysiology of bipolar illness. Earlier work had
      established reduction in sodium-potassium-activated adenosine triphosphatase
      (Na(+)-K(+)-ATPase) activity as a consistent marker of mood in bipolar illness
      but had only partially illuminated mechanisms of the action of lithium. Now,
      advances from research in diabetic neuropathy suggest that inositol phosphate and
      diacylglycerol metabolism are indeed linked to Na(+)-K(+)-ATPase activity. The
      data are compatible with a model in which a primary decrease in Na(+)-K(+)-ATPase
      activity in bipolar patients can stimulate an increase in phosphoinositide
      hydrolysis, thereby generating the equivalent of a second messenger signal in the
      absence of a first message. Lithium appears to act by blocking this false second
      message.

PMID- 8286933
TI  - Depression and anxiety following traumatic brain injury.
AB  - The frequency, course, and clinical correlates of generalized anxiety disorder
      (GAD) and its relationship to major depression were examined in 66 patients with
      traumatic brain injury (TBI). Of 66 TBI patients, 7 (11%) had both GAD and major
      depression; 10 (15%) had major depression without GAD. Median duration was 1.5
      months for nonanxious depressions, 7.5 months for anxious depressions, and 1.5
      months for concurrent GAD. Anxious depressions were also associated with right
      hemisphere lesions, whereas major depressions alone were associated with left
      anterior lesions. These findings suggest that anxious major depression and major
      depression following TBI may be two different disorders with different underlying
      etiological mechanisms and perhaps differential response to treatment.

PMID- 8286934
TI  - Developmental brain anomalies in schizophrenia and bipolar disorder: a controlled
      MRI study.
AB  - Many of the structural brain abnormalities found in schizophrenia (SC) and
      bipolar disorder (BD) over the past decade are believed to represent impaired
      neurodevelopmental processes. The authors hypothesized that incidental
      developmental anomalies would be more frequently present in the brains of
      subjects with SC and BD compared with healthy control subjects. The authors
      systematically assessed the MRI scans of 167 subjects (SC = 67,
      BD/schizoaffective = 63, healthy control subjects = 37) for the presence of 23
      developmental anomalies involving cortical and subcortical structures. No excess
      neurodevelopmental anomalies were found in the schizophrenic or
      bipolar/schizoaffective groups. These findings do not support the hypothesis that
      SC and BD are associated with an excess of gross neurodevelopmental brain
      anomalies.

PMID- 8286935
TI  - SPECT findings in patients with primary mania.
AB  - Five patients with a manic episode and 7 age-comparable control subjects were
      studied with single-photon emission computed tomography and [99mTc]d,l
      hexamethylpropyleneamine oxime. Manic patients showed significantly lower blood
      flow in the basal portion of the right temporal lobe compared with normal control
      subjects. Moreover, manic patients showed a left-right asymmetry (a significantly
      lower perfusion in the right versus left temporal basal cortex), as well as a
      dorsal-ventral asymmetry (a significantly lower perfusion in the right temporal
      basal versus dorsal cortex). These findings suggest that the right basotemporal
      cortex may play an important role in the production of primary mania.

PMID- 8286936
TI  - Brain regions involved in recognizing facial emotion or identity: an oxygen-15
      PET study.
AB  - The functional neuroanatomy of emotion recognition is inadequately understood
      despite well-documented clinical situations where emotion recognition is impaired
      (aprosodia). Oxygen-15 water positron-emission tomography (PET) was used to study
      9 healthy women volunteers during three match-to-sample conditions, each repeated
      twice: a study task matching facial emotions and control tasks matching spatial
      positions or facial identity. Results suggest that the higher order functional
      neural network for recognizing emotion in visual input likely involves the right
      anterior cingulate and the bilateral inferior frontal gyri.

PMID- 8286937
TI  - A preliminary study of cortical S2 serotonin receptors and cognitive performance
      following stroke.
AB  - Cortical serotonin receptor binding was measured with positron-emission
      tomography (PET) in uninjured regions of cortex in 26 stroke patients. Cognitive
      function was assessed with the Mini-Mental State Exam (MMSE) and a
      neuropsychological test battery. Left frontal cortex serotonin binding was
      correlated positively with MMSE total score (r = 0.50, P = 0.01) and with the
      MMSE concentration, writing, and copying tasks (r = 0.42, 0.56, 0.53,
      respectively; P < 0.05). Tests of orientation and repetition of difficult phrases
      were significantly correlated with serotonin binding (r = 0.53 and 0.52,
      respectively; P < 0.05). These findings suggest that cognitive performance after
      stroke may be influenced by alterations in the serotonergic system.

PMID- 8286938
TI  - Increased prevalence of electrophysiological abnormalities in children with
      psychological, physical, and sexual abuse.
AB  - This retrospective study examined the association between abuse history and
      neurological abnormalities in 115 consecutive patients admitted to a child and
      adolescent psychiatric inpatient unit. Increased electrophysiological
      abnormalities were found in abused patients compared with non-abused patients
      (54.4% vs. 26.9%, P = 0.021), predominantly in the left side of the frontal,
      temporal, or anterior region (P = 0.036). This may support the hypothesis that
      early abuse alters brain development, particularly limbic structures. However, a
      large-scale prospective longitudinal assessment study is needed to interpret this
      association. Possible clinical consequences of relatively preserved right frontal
      function are discussed.

PMID- 8286939
TI  - EEG power modifications in panic disorder during a temporolimbic activation task:
      relationships with temporal lobe clinical symptomatology.
AB  - Computerized EEG activity derived from the temporal lobes was investigated in
      normal subjects and panic disorder patients with and without depersonalization
      and/or derealization, in a resting condition and during an odor stimulation task.
      Panic patients without depersonalization or derealization showed an increase of
      fast and a decrease of slow activities independent of odor stimulation. Panic
      patients with depersonalization and/or derealization showed an increase of slow
      activity and bilateral lack of responsiveness in the fast alpha frequency band
      during odor stimulation. Findings suggest there are different EEG patterns in the
      temporal regions of the two different groups of panic patients during rest and
      activating conditions.

PMID- 8286940
TI  - Xenon-133 SPECT-determined regional cerebral blood flow in Alzheimer's disease:
      what is typical?
AB  - A study of 76 consecutive xenon-133 SPECT studies of regional cerebral blood flow
      was undertaken to determine the frequency of various patterns of blood flow in
      cases of clinically diagnosed probable and possible Alzheimer's disease. The
      reference tomographic section was a slice 6 cm above and parallel to the
      canthomeatal line. With the use of this technique, the "classic" finding of
      bilateral temporoparietal (TP) flow reductions as the sole abnormality occurred
      in only 28% of cases. Bilateral TP reductions accompanied by bilateral or
      unilateral frontal flow reductions were nearly as common (24%), and other
      patterns accounted for the other 48% of cases.

PMID- 8286941
TI  - Cerebral perfusion and neuropsychological consequences of chronic cocaine use.
AB  - Research indicates that cocaine significantly constricts the cerebral vasculature
      and can lead to ischemic brain infarction. Long-term effects of intermittent or
      casual cocaine use in patients without symptoms of stroke or transient ischemic
      attack were investigated. Single-photon emission computed tomography with xenon
      133 and [99mTc]hexamethylpropyleneamine oxime, magnetic resonance imaging, and
      selected neuropsychological measures were used to study cerebral perfusion, brain
      morphology, and cognitive functioning. Patients were drug free for at least 6
      months before evaluation. All showed regions of significant cerebral
      hypoperfusion in the frontal, periventricular, and/or temporal-parietal areas.
      Deficits in attention, concentration, new learning, visual and verbal memory,
      word production, and visuomotor integration were observed. This study indicates
      that long-term cocaine use may produce sustained brain perfusion deficits and
      persistent neuropsychological compromise in some subgroups of cocaine-abusing
      patients.

PMID- 8286942
TI  - ECT in a patient with a frontal craniotomy and residual meningioma.
AB  - Electroconvulsive therapy (ECT) was used to treat a patient with a large left
      frontal craniotomy and remaining frontal meningioma. Treatment was successful and
      uneventful. ECT should be considered in the treatment of drug-resistant depressed
      patients with craniotomies and remaining tumor.

PMID- 8286943
TI  - Anticonvulsant use in the treatment of manic syndromes in patients with HIV-1
      infection.
AB  - A retrospective chart review identified 11 patients with type 1 human
      immunodeficiency virus (HIV) who presented to an HIV/AIDS psychiatric service
      with an acute manic episode. Demographic data, neurodiagnostic studies, and
      treatment results are discussed. Abnormal brain magnetic resonance imaging
      significantly predicted poor tolerance of lithium and neuroleptics.
      Anticonvulsants were an effective alternative.

PMID- 8286944
TI  - Case conference: behavior change, hallucinations, and memory loss in a 25-year
      old man.

PMID- 8286945
TI  - Delirium and DSM-IV.

PMID- 8286946
TI  - Recombinant Escherichia coli RNA polymerase: purification of individually
      overexpressed subunits and in vitro assembly.
AB  - New improved methods were developed for the purification to apparent homogeneity
      of alpha, beta, beta', and sigma subunits of Escherichia coli RNA polymerase
      (RNAP) from corresponding overproducing strains. The purified subunits were
      assembled into enzymatically active RNAP holoenzyme (alpha 2 beta beta' sigma)
      using the optimal subunit molar ratio (alpha:beta:beta':sigma = 2:8:4:1) at a
      total protein concentration of 0.5 mg/ml. The presence of sigma subunit and 10
      microM ZnCl2 in the reconstitution mixture increased the yield of RNAP
      approximately 4 times. The assembled RNA polymerase was purified by two
      successive chromatographic steps using size-exclusion Superose 6 and anion
      exchange Mono Q FPLC columns, which resulted in the electrophoretically
      homogeneous holoenzyme with overall yield of 56%. The specific activity of the
      recombinant RNAP estimated by the standard T4 transcription assay was 6.5 nmol of
      [3H]UTP incorporated into acid-insoluble RNA product per microgram of RNAP per 1
      h.

PMID- 8286947
TI  - The purification and properties of ferredoxin-NADP(+)-oxidoreductase from roots
      of Pisum sativum L.
AB  - A ferredoxin-NADP(+)-oxidoreductase (FNR) was purified to homogeneity from pea
      root plastids to a specific activity of 200 nkat.mg protein-1, following acetone
      precipitation and ferredoxin affinity chromatography. The molecular weight of the
      enzyme was estimated to be 36,000 and 33,800 by SDS-polyacrylamide gel
      electrophoresis and molecular exclusion chromatography, respectively. The
      absorption spectrum of the enzyme suggests it contains flavin as a prosthetic
      group. The enzyme requires NADPH and did not use NADH as an electron donor. The
      Km values for NADPH and ferredoxin were calculated to be 28 and 5 microM,
      respectively. The enzyme exhibited optimal activity at pH 8.0. Although
      resembling the leaf enzyme in most properties, amino terminal sequencing
      demonstrates clear differences between the leaf and root proteins and suggests
      closer homology of the pea root enzyme with the enzyme from spinach roots. A
      polyclonal antibody against the pea root plastid enzyme was raised by the
      immunization of rabbits. Judging by immunodiffusion only partial identity was
      observed between the root plastid and chloroplast FNR. The root plastid FNR
      enzyme activity was precipitated with increasing concentrations of the antibody,
      in contrast to the chloroplast enzyme which was not inhibited. The potential
      usefulness of these antibodies is discussed.

PMID- 8286948
TI  - Purification of the glyoxylate cycle enzyme malate synthase from maize (Zea mays
      L.) and characterization of a proteolytic fragment.
AB  - A purification scheme is described for the glyoxylate cycle enzyme malate
      synthase from maize scutella. With our procedure, large amounts of extremely pure
      enzyme can easily be prepared. Purification involves a heat denaturation step,
      followed by ammonium sulfate precipitation, and chromatography on DEAE-cellulose
      and Blue Dextran-Sepharose. Catalase and malate dehydrogenase, which are the most
      persistent contaminants, are completely removed by this procedure. Maize malate
      synthase is an octameric protein with a subunit molecular weight of 64 kDa.
      Purity of the enzyme preparation was demonstrated by SDS-polyacrylamide gel
      electrophoresis and by isoelectric focusing (pI = 5.0). Pure malate synthase can
      be stored without appreciable loss of activity at -70 degrees C in 200 mM Hepes
      buffer containing 6 mM MgCl2 and 2 mM 2-mercaptoethanol, pH 7.6. Maize malate
      synthase contains no covalently linked carbohydrate residues. The enzyme requires
      Mg2+ ions for activity. From circular dichroism measurements we estimate that the
      secondary structure of the enzyme consists of 30% alpha-helical and almost no
      (5%) beta-pleated sheet segments. A 45-kDa polypeptide, which contaminates malate
      synthase preparations if the purification starts from seedlings older than 2.5
      days, is shown to be a degradation product of malate synthase. Together with full
      length chains, these 45-kDa polypeptides are able to take part in octameric
      oligomer formation.

PMID- 8286949
TI  - The preparation of endotoxin-free L-methionine-alpha-deamino-gamma
      mercaptomethane-lyase (L-methioninase) from Pseudomonas putida.
AB  - Many types of human and animal tumors have an absolute requirement for
      methionine. This requirement can be satisfied by homocysteine only in normal
      cells and tissues. Therefore, methionine may be an important target in cancer
      therapy. To attack this target we have purified endotoxin-free methioninase from
      Pseudomonas putida by a novel and simple procedure. This procedure involves (1) a
      heat step of the cell extract at 60 degrees C for 8 min, (2) DEAE-Toyopearl ion
      exchange chromatography, (3) DEAE-Sephadex A50 ion-exchange gel filtration
      chromatography, and (4) affinity chromatography on Acticlean to remove the
      endotoxin bound to the enzyme. The yield for this purification was up to 80%. The
      methioninase has four subunits of approximate molecular weight 43 kDa. This is
      the first methodology for methioninase that allows rapid purification with high
      yield and separation from endotoxin suitable for in vivo efficacy testing against
      methionine-dependent tumors in animal models.

PMID- 8286950
TI  - A four-step, inexpensive protocol for large-scale purification of goat uterine
      estrogen receptor.
AB  - A relatively inexpensive yet highly efficient and extremely rapid procedure has
      been developed for the isolation and purification of estrogen receptor from the
      goat uterine cytosol. Greater than 1 mg of purified receptor protein could be
      obtained from 75 g of uterine tissue within a period of < 24 h, following this
      protocol. The procedure does not require the use of an ultracentrifuge, a cold
      room, or a column chromatography setup. The entire isolation procedure, which
      involves adsorption to and selective elution from different chromatography
      matrices, is carried out at the laboratory bench using beakers kept in an ice
      bath. Antibodies raised against this receptor cross-react with the goat uterine
      estrogen receptor activation factor, a DNA binding protein having no capacity to
      bind estradiol but which dimerizes with the nonactivated estrogen receptor, an
      estrogen receptor incapable of binding to DNA on its own.

PMID- 8286951
TI  - One-step purification of plant ferredoxin-NADP+ oxidoreductase expressed in
      Escherichia coli as fusion with glutathione S-transferase.
AB  - Complementary DNA sequences encoding the mature form of pea ferredoxin-NADP+
      reductase were cloned in-frame at the 3' end of the Schistosoma japonicum
      glutathione S-transferase gene in the expression vector pGEX-3X (Smith and
      Johnson, Gene 67, 31-40, 1988). A spacer sequence linking the two genes was
      modified to provide a proteolytic site just before the first amino acid residue
      of mature pea reductase. When introduced into competent Escherichia coli cells
      and induced, the resulting plasmid (pGF205) directed the expression of a 60-kDa
      immunoreactive peptide that results from the fusion between glutathione S
      transferase and ferredoxin-NADP+ reductase sequences. The fused protein could be
      purified in a single step by selective absorption onto glutathione-agarose beads,
      followed by elution with free glutathione. It showed both transferase and
      reductase activities. Removal of the transferase portion by cleavage with the
      restriction protease Xa rendered ferredoxin-NADP+ reductase electrophoretically
      homogeneous. The purified transgenic enzyme showed kinetic and spectroscopic
      properties that were similar to those reported for the plant flavoprotein,
      indicating that, even when fused to the 27-kDa transferase portion, the reductase
      was still able to assemble FAD and to acquire an active conformation in the
      bacterial host. The expression-purification protocol employed here allows the
      isolation of up to 1 mg of active ferredoxin-NADP+ reductase/g of transformed
      cells. The system is potentially useful for the purification of activity-impaired
      forms of the flavoprotein.

PMID- 8286952
TI  - Purification and characterization of recombinant polymeric hemoglobin P1 of
      Glycera dibranchiata.
AB  - The apoprotein of component P1 of the polymeric fraction of the intracellular
      hemoglobin of the marine polychaete Glycera dibranchiata has been expressed at a
      high level in Escherichia coli. The expressed globin was reconstituted with heme
      and purified. The N-terminal sequence of the recombinant P1 is identical to the
      cDNA-derived sequence of cloned P1 (Zafar et al., Biochem. Biophys. Acta, 1041,
      117-123, 1990). Gel filtration, SDS-PAGE, optical spectra over the range 200-650
      nm, and circular dichroism over the range 200-250 nm of the purified recombinant
      P1 were very similar to the polymeric fraction of native Glycera hemoglobin. The
      molar ellipticity at 222 nm provided an estimate of 77% for the alpha-helical
      content of the recombinant P1, in excellent agreement with that calculated from
      the crystal structure of Glycera monomeric component M-II. Although the oxygen
      binding affinity of the recombinant P1 is higher than that of the polymeric
      fraction of Glycera hemoglobin (3-4 torr vs 7-13 torr), which consists of at
      least six different single-chain hemoglobins, the Hill coefficient is lower (1.0
      1.2 vs 1.2-1.4).

PMID- 8286953
TI  - Purification of glutamine transaminase K/cysteine conjugate beta-lyase from rat
      renal cytosol based on hydrophobic interaction HPLC and gel permeation FPLC.
AB  - Cysteine conjugate beta-lyase (beta-lyase, EC 4.4.1.13) was purified to
      homogeneity from rat renal cytosol using a new and highly efficient method, based
      on C3-hydrophobic interaction (HI) high-performance liquid chromatography (HPLC)
      in combination with gel permeation fast protein liquid chromatography. The purity
      of the enzyme was judged from SDS-PAGE and C18-reversed-phase HPLC. The beta
      lyase was estimated to be a homodimer consisting of a 47,400-Da subunit with
      absorption maxima at 280 and 420-430 nm. The specific activity of the purified
      beta-lyase toward S-(1,2-dichlorovinyl)-L-cysteine (1,2-DCVC) in the presence of
      alpha-keto-gamma-methiolbutyric acid (KMB) was 6.4 mumol/min/mg protein, which is
      by far the highest value so far reported. Kinetic analysis of 1,2-DCVC metabolism
      by the enzyme in the presence of KMB gave Km and Vmax values of 0.33 mM and 8.4
      mumol/min/mg protein, respectively. No significant activity of the purified
      enzyme was detectable with S-2-benzothiazolyl-L-cysteine up to 2 mM. The purified
      enzyme also had glutamine transaminase K activity (EC 2.6.1.64) as assayed with
      phenylalanine and KMB as substrates. This specific activity was 16.0
      mumol/min/mg. Amino acid analysis of the purified beta-lyase was carried out and
      was found to be closely similar to the amino acid composition of five other
      pyridoxal phosphate (PLP)-containing amino acid amino-transferases. This suggests
      that glutamine transaminase K/cysteine conjugate beta-lyase is a typical member
      of the PLP-containing aminotransferase group.

PMID- 8286954
TI  - Purification of concentrated hemoglobin using organic solvent and heat treatment.
AB  - A simple method for obtaining a purified and concentrated hemoglobin (Hb)
      solution (25 g/100 ml) from human red blood cells has been established. To
      prevent MetHb formation during the purification procedure, Hb in red blood cells
      was carbonylated in advance, and then washed red blood cells were mixed with
      organic solvents such as diethyl ether or dichloromethane for hemolysis and
      removal of stroma. The Hb solution was isolated by centrifugation (1900g) with
      the high removal efficiency of phospholipid (> 99.8%). After the solution was
      heated (60 degrees C, 1 h), the precipitates were removed by centrifugation. The
      purity of Hb was confirmed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Isoelectric focusing and oxygen-binding properties of the
      obtained Hb solution demonstrated its purity and showed no denaturation of
      globin. This purification procedure is applicable to large-scale production of
      the purified Hb.

PMID- 8286955
TI  - Expression in Escherichia coli of the cloned polyhedrin gene of Bombyx mori
      cytoplasmic polyhedrosis virus.
AB  - Cloned cDNA of genomic segment 10 of Bombyx mori cytoplasmic polyhedrosis virus
      (CPV) was placed downstream from the lambda PL promoter in expression plasmid
      pRC23 and expressed in Escherichia coli cells. A polypeptide of the same
      molecular weight (28 kDa) as natural polyhedrin was synthesized at the level of
      approximately 10% of total host cell protein. This polypeptide was identified as
      CPV polyhedrin (r-polyhedrin) after comparative studies. The r-polyhedrin did not
      form any crystalline structure in E. coli cells but instead accumulated in the
      form of an insoluble inclusion body, even though natural polyhedrin is known to
      form a crystalline matrix (polyhedra) in infected insect cells. The purified r
      polyhedrin complex, like natural polyhedra, was not soluble in neutral or acidic
      buffer but soluble in alkaline buffer. Upon solubilization, the r-polyhedrin
      complex did not undergo proteolytic degradation, while natural polyhedra were
      digested into small peptides by the associated protease. Incubation of r
      polyhedrin with natural polyhedra in alkaline buffer, however, degraded the r
      polyhedrin, resulting in an identical profile of peptide products to that of
      natural polyhedra. These results indicate that even though r-polyhedrin molecules
      produced in E. coli cells are not in the natural conformation, the molecules can
      present the identical cleavage sites to the polyhedra-associated alkaline
      protease. Experiments showed that the alkaline protease was associated with the
      matrix of polyhedra and not with virus particles.

PMID- 8286956
TI  - The Chinese total diet study in 1990. Part I. Chemical contaminants.
AB  - The Chinese total diet study in 1990 estimated the dietary intake of 24 chemical
      contaminants and 72 nutrients from 4 market baskets collected and prepared in 12
      provinces. Twelve food group composites were made for each regional market
      basket. The overall dietary Pb, Cd, Hg, hexachlorocyclohexane HCH, and DDT
      intakes were well below their corresponding acceptable daily intakes. However,
      the Pb content of eggs from the 2 southern regions exceeded the tolerance limit.
      The Hg content of legumes just reached the tolerance limit, and Hg in eggs from
      the North 1 region exceeded the tolerance limit. The dietary HCH intake has
      decreased significantly since the 1980s, but dietary DDT intake has decreased
      rather slowly. Five organophosphorus pesticides were detected out of a total of
      12 organophosphorus pesticides analyzed. Among them, methamidophos was the most
      outstanding. The intake of total committed dose equivalents (CDEs) of the 6
      radionuclides was 0.24 mSv/a; only 1.5% was accounted for by 90Sr and 137Cs.
      210Pb, 210Po, 226Ra, and 228Ra accounted for 98.5% of the total CDEs. The main
      food sources of those radionuclides were cereals, vegetables, and aquatic foods.
      Aflatoxin B1 was detected at very low levels only in the cereal composite of the
      North 1 region. Aflatoxin M1 was not detected in any of the milk and milk
      products. The overall results show that there is no significant environmental
      contamination of the average Chinese diet.

PMID- 8286957
TI  - The Chinese total diet study in 1990. Part II. Nutrients.
AB  - This paper reports the intakes of 72 nutrients and their dietary sources obtained
      from the Chinese total diet study in 1990. Most of the nutrient intakes are close
      or equal to their corresponding recommended daily allowances (RDAs). Both the
      total energy intake (2203 kcal) and the proportions contributed by protein, fat,
      and carbohydrate meet the current Chinese RDAs and the World Health Organization
      (WHO) nutrient goals. The average protein intake was 64 g/day. The intake of
      essential amino acids all exceeded the Chinese RDA, and their proportions were
      generally consistent with the WHO recommended pattern. The average fat intake was
      51.2 g/day (21.2% of the total energy intake). However, the dietary fat intake
      has been increasing significantly in the Chinese diet and the proportion of
      animal fat has reached 53% of the total fat intake. The total saturated:total
      monounsaturated: total polyunsaturated fatty acid ratio was 1.0:1.5:1.0. Although
      the average cholesterol intake was only 179 mg/day, it was 248 mg/day in the
      South 1 region. The intakes of thiamine and riboflavin were below the RDA.
      Retinol intakes in all the 4 regions were low. Most (80%) of the retinol
      (equivalent) intakes were from carotenoids. The average intake of total
      tocopherol was 89% of the RDA, and among the 4 regions, only the South 2 region
      has relatively low intake. The intakes of iron, copper, manganese, sodium, and
      phosphorus were adequate. The intakes of calcium, zinc, and potassium were
      insufficient, and intakes of selenium and magnesium were a little low. High
      sodium and low potassium intake is a traditional problem in the Chinese diet.

PMID- 8286958
TI  - Survey of benzene in foods by using headspace concentration techniques and
      capillary gas chromatography.
AB  - Recently, the combination of sodium or potassium benzoate with ascorbic acid was
      shown to produce low levels (ng/g) of benzene in fruit-flavored soft drinks. The
      presence of benzene also was reported in butter, eggs, meat, and certain fruits;
      levels of these findings ranged from 0.5 ng/g in butter to 500-1900 ng/g in eggs.
      Because benzoates are widely used as food preservatives, a limited survey of
      other foods containing added benzoate salts was conducted to investigate the
      potential for benzene formation. Selected foods that did not contain added
      benzoates but were previously reported to contain benzene were analyzed for
      comparison. More than 50 foods were analyzed by purge-and-trap or static
      headspace concentration and capillary gas chromatography. Benzene was quantitated
      by using the method of standard additions, and its identity was confirmed by mass
      selective detection. Results of this limited survey show that foods without added
      benzoates (including eggs) contained benzene at levels equal to or less than 2
      ng/g. Slightly higher levels were present in some foods and beverages containing
      both ascorbic acid and sodium benzoate.

PMID- 8286959
TI  - Pesticide residues in composited milk collected through the U.S. Pasteurized Milk
      Network.
AB  - The U.S. Food and Drug Administration (FDA) has implemented a comprehensive
      monitoring program to determine the incidence and levels of organohalogen
      pesticide residues in milk representing most of the U.S. supply consumed in
      metropolitan areas. Residue findings for 806 composite milks collected through
      the Pasteurized Milk Program by the U.S. Environmental Protection Agency (EPA) in
      1990-1991 are reported. Milk was collected on a monthly basis from 63 stations
      selected by EPA for radionuclide monitoring. These stations provide an estimated
      80% of the milk delivered to U.S. population centers. At each station, milk from
      selected sources had been composited to represent the milk routinely consumed in
      its metropolitan area. Portions of these composites were forwarded to an FDA
      contract laboratory for pesticide residue analysis. Pesticide residues were found
      in 398 (49.4%) of 806 test samples, on the basis of a 0.0005 ppm limit of
      detection for each residue on a whole-product basis. A total of 455 occurrences
      of pesticide residues were found; p,p'-DDE and dieldrin accounted for 384 (84.4%)
      of these occurrences. The highest level was 0.019 ppm p,p'-DDE.

PMID- 8286960
TI  - Survey of total tetrahydrophthalimide in baby foods using both enzyme-linked
      immunosorbent assay and gas chromatography/mass spectrometry: a comparative
      study.
AB  - An enzyme-linked immunosorbent assay (ELISA) method was compared with a gas
      chromatographic/mass spectrometric (GC/MS) method for determining the
      concentration (in parts per million) of the combination of captan and its
      degradation product tetrahydrophthalimide (THPI) in 13 fruit samples and in a
      survey of baby foods. Ninety baby foods (49 fruits, 28 juices, and 13 vegetables)
      from 2 different suppliers were sampled. All captan in the samples was converted
      to THPI before each analysis. None of the samples contained a concentration of
      combined captan and THPI that violated the maximum residue limit of 5.0 ppm.
      Eight samples of baby food tested positive for THPI at levels ranging from 0.019
      0.041 ppm by the GC/MS method, whereas 20 samples tested positive in the ELISA
      assay. All samples that tested positive with the GC/MS method also tested
      positive with the ELISA method. Thirteen percent of the baby food samples tested
      false positive with the ELISA method. The ELISA assay also gave higher values
      than the GC/MS method. The ELISA method can be effectively used as a primary
      screening tool to select samples testing positive for THPI. The concentration of
      THPI in these samples can then be verified using the GC/MS method.

PMID- 8286961
TI  - Liquid chromatographic determination of moxidectin residues in cattle tissues and
      confirmation in cattle fat by liquid chromatography/mass spectrometry.
AB  - Moxidectin, a potent new endo- and ectoparasitic agent, is determined in cattle
      tissues by liquid chromatography (LC) with fluorescence detection. Moxidectin
      residues in cattle fat are confirmed with thermospray LC/mass spectrometry (MS).
      Moxidectin is extracted from the tissue with acetonitrile; the extract is
      partitioned with hexane, concentrated, and reacted with acetic anhydride, 1
      methylimidazole, and dimethylformamide to produce a fluorescent product. The
      validated sensitivity of the LC/fluorescence method was 10 ppb, with a limit of
      detection typically between 1 and 2 ppb. Average recoveries from cattle fat,
      muscle, liver, and kidney were 99, 95, 89, and 92%, respectively. LC/MS
      confirmatory method determined the underivatized parent compound following the
      acetonitrile-hexane partitioning step, with an average recovery of 108% at the
      250 ppb level in cattle fat.

PMID- 8286962
TI  - Simultaneous determination of nitrofurazone and furazolidone in shrimp (Penaeus
      vannamei) muscle tissue by liquid chromatography with UV detection.
AB  - A liquid chromatographic (LC) method was developed for the simultaneous
      determination of nitrofurazone (NFZ) and furazolidone (FZD) in shrimp muscle
      tissue. The drugs are extracted from the tissue with acetonitrile, and the lipids
      and lipophilic pigments are removed from the extract with hexane. The remaining
      acetonitrile extract is evaporated by rotary evaporation, and the resultant
      residues are dissolved with LC-grade water, applied to a preconditioned C18 solid
      phase extraction column, and eluted with acetonitrile. The acetonitrile eluant is
      then dried under nitrogen, and the resultant drug residues are dissolved with
      mobile phase and filtered. The drugs are determined by LC by using a C18 reversed
      phase (octyldecylsilyl Hypersil) column, a mobile phase of acetonitrile--1%
      aqueous acetic acid (25 + 75, v/v), and a photodiode array UV detector at 375 nm.
      NFZ and FZD were determined in shrimp tissue at each of 5 spiking levels (64, 32,
      16, 8, and 4 ng drug/g tissue). Absolute recoveries ranged from 70.6 to 78.4%,
      and relative standard deviations ranged from 4.0 to 13.6%. The limit of detection
      of pure standard of each drug was approximately the equivalent of 1 ng drug/g
      tissue, and the limit of determination in a sample was 4 ng drug/g tissue.

PMID- 8286963
TI  - Effectiveness of the Bacteriological Analytical Manual culture method for the
      recovery of Shigella sonnei from selected foods.
AB  - The relative retention of the indigenous morphological, biochemical, and
      serological characteristics by Shigella sonnei was tested under various storage
      conditions (room temperature, refrigeration, freezing at -20 degrees C and at -70
      degrees C, and lyophilization). The use of a selective (desoxycholate citrate)
      agar rather than a nonselective (brain heart infusion) agar gave a lower
      conversion rate of smooth to rough colonies, and the percentage of rough colonies
      derived from cultures stored for prolonged periods increased under all
      conditions. With respect to biochemical characteristics, there were no major
      differences in the reactions of smooth vs rough variants. For serological
      characteristics, smooth variants agglutinated more readily in homologous antisera
      than did rough variants. S. sonnei populations maintained at -70 degrees C with
      glycerol remained reasonably stable and were used in recovery studies. Up to six
      foods (potato salad, chicken salad, cooked salad shrimp, lettuce, raw ground
      beef, and raw oysters) were inoculated with unstressed, chill-stressed, or freeze
      stressed S. sonnei cells. Test portions (25 g) were inoculated with serial 10
      fold dilutions of culture and subsequently analyzed by the culture method
      described in the U.S. Food and Drug Administration's Bacteriological Analytical
      Manual. It was found that the method was relatively ineffective for the recovery
      of S. sonnei from raw ground beef and raw oysters.

PMID- 8286964
TI  - Liquid chromatographic determination of aflatoxin M1 in milk powder using
      immunoaffinity columns for cleanup: interlaboratory study.
AB  - A liquid chromatographic method for determining low aflatoxin M1 concentrations
      in milk was evaluated in an International Dairy Federation (IDF) interlaboratory
      study. The study involved 16 participants from 11 countries. The method, chosen
      after a comparison of several methods by a preparatory group, uses an
      immunoaffinity column for cleanup. As the sample passes through the column,
      antibodies selectively bind with aflatoxin M1 (antigen) present and form an
      antibody-antigen complex. All other components of the sample matrix are washed
      off the column with water. Then, aflatoxin M1 is eluted from the column with
      acetonitrile, which is collected. Final determination is carried out by reversed
      phase liquid chromatography with fluorescence detection. Over the tested range
      (80-600 ng aflatoxin M1/kg milk powder), an RSDR ranging from 11 to 23% was
      obtained by analyzing 24 samples (blind duplicates), 2 samples of which were
      blanks.

PMID- 8286965
TI  - Semiautomatic determination of furanic aldehydes in food and pharmaceutical
      samples by a stopped-flow injection analysis method.
AB  - A kinetic study of the reactions of 5-hydroxymethyl-2-furfuraldehyde and furfural
      with 2-thiobarbituric acid (TBA) by a stopped-flow flow injection analysis
      technique has been undertaken. A semiautomatic method for the analytical
      determination of these furanic aldehydes is proposed on the basis of reaction
      with TBA. The proposed stopped-flow method was successfully applied to several
      commercial pharmaceutical preparations and food samples. The procedure is faster
      than the earlier procedure for determination of these compounds in foods and
      pharmaceuticals.

PMID- 8286966
TI  - Speciation analysis of organolead compounds in wine by capillary gas
      chromatography/microwave-induced-plasma atomic emission spectrometry.
AB  - A method was developed for the speciation analysis of ionic organolead compounds
      in wine. The analytes were extracted as diethyldithiocarbamate complexes into
      hexane and propylated with a Grignard reagent. The derivatized extract was
      analyzed by capillary gas chromatography/microwave-induced-plasma atomic emission
      spectrometry. The method of standard additions was used for calibration to
      correct for variable recoveries and signal enhancements. Red, rose, and white
      wines from southern France were analyzed. Trimethyllead was the ubiquitous
      species. The wines made from grapes grown close to industrial zones showed
      elevated concentrations of ethyllead species. The concentrations of methyllead
      and ethyllead found in wines were compared with the concentrations of organolead
      found in rain water and plant sap collected in the viticultural regions. The
      ratio of methyllead to ethyllead in wines greatly exceeded the same ratio found
      in atmospheric deposits.

PMID- 8286967
TI  - Determination of volatile chemicals released from microwave-heat-susceptor food
      packaging.
AB  - Microwave heat susceptors that convert electromagnetic energy to heat attain high
      temperatures that make it possible to cook some foods to golden crispness in a
      microwave oven. Susceptors are typically packaged with foods intended for
      microwave use, e.g., waffles, pizzas, and french fries. The high temperatures >
      302 degrees F used to cook some foods release trace levels of volatile chemicals
      from metalized polyester film, adhesive, and paper packaging materials; these
      volatile chemicals may be absorbed by the food. We simulated microwave susceptor
      cooking conditions and developed protocols by using headspace concentration
      capillary gas chromatography and mass spectrometry to identify volatile chemicals
      released from heated susceptors. We purchased a limited, cross-sectional sample
      of local retail microwave food products packaged with susceptors and used our
      protocol to analyze 10 different susceptor products. Although more than 140
      unique chromatographic peaks were tabulated, only 44 volatile chemicals were
      identified, including 1,1,1-trichloroethane, benzene, and 2-(2
      butoxyethoxy)ethanol, which were derived primarily from the paper and adhesive
      susceptor components. No one susceptor contained all the identified substances.
      The standard additions technique was the preferred method for quantitation.
      Trichloroethane and 2-(2-butoxyethoxy)ethanol were present in several products at
      75-122 micrograms/in.2 of susceptor surface area. Benzene was found in 3
      susceptors at < or = 0.22 microgram/in.2 levels. Examination indicates that
      adhesives used in more recent susceptor products were reformulated to remove even
      this trace level of benzene.

PMID- 8286968
TI  - Method modification for liquid chromatographic determination of thiamine,
      riboflavin, and pyridoxine in medical foods.
AB  - A reversed-phased ion pair liquid chromatographic method developed for the
      simultaneous determination of thiamine (B1), riboflavin (B2), and pyridoxine (B6)
      in perchloric acid extracts of infant formulas was modified to include medical
      foods. UV detection of B1 and B2 was replaced by fluorescence detection, which
      resulted in improved sensitivity and specificity. B1 was detected by fluorescence
      after conversion to thiochrome by a postcolumn reaction with sodium hydroxide and
      potassium ferricyanide. The method uses a mobile phase of water, acetonitrile,
      hexanesulfonic acid sodium salt, ammonium hydroxide, and phosphoric acid adjusted
      to pH 3.6. The column is a 300 x 3.9 mm Nova Pak C18. Limits of detection were
      0.05 microgram/mL for B1 and B2 and 0.01 microgram/mL for B6 by fluorescence
      detection. The system reproducibility was evaluated by completing 10 repetitive
      determinations on a medical food that gave a coefficient of variation of 5.9,
      6.0, and 10.7% for B1, B2, and B6, respectively. Mean recoveries (n = 10) were
      111, 96.3, and 113% for B1, B2, and B6, respectively. The results compared
      favorably with those by AOAC Official Methods 942.23, 940.33, and 961.15 for B1,
      B2, and B6, respectively.

PMID- 8286969
TI  - Determination of menthol in honey by gas chromatography.
AB  - A gas chromatographic method was developed for the determination of L-menthol in
      honey at levels as low as 0.1 ppm. The method includes steam distillation and
      hexane extraction with an internal standard (2,6-dimethylphenol). Beehives
      treated to control Acarapis woodi over 21 days with 30-60 g L-menthol contained L
      menthol residues in honey and beeswax. L-Menthol was found only in treated
      portions of the hive and not later transferred to added honey supers. The highest
      levels of residues in honey (18 ppm) and beeswax (2790 ppm) were found when pure
      L-menthol was adsorbed into foam strips placed on top of the hives. L-Menthol
      residues in honey were not reduced by storage in open containers at room
      temperature for up to 55 days. Untrained panelists could not detect L-menthol in
      honey until the levels approached 36 ppm.

PMID- 8286970
TI  - Analyte stability study of N-methylcarbamate pesticides in beef and poultry liver
      tissues by liquid chromatography.
AB  - To optimize conditions for sample collection, preparation, storage, and analysis
      and to assure the validity of our previously published liquid chromatographic
      (LC) method for carbamate analysis in tissue, stabilities of 16 N
      methylcarbamates in beef, duck, and chicken liver tissues were studied by using 2
      sampling protocols. Tissue samples were fortified at room temperature to a
      concentration 5 to 10 times greater than either the Environmental Protection
      Agency tolerance level for each compound (if established) or the concentration
      used in the previously published method. Thereafter, samples were continuously
      frozen at -4 degrees C for varying time intervals. In the first study, samples
      were analyzed one day (initial) and 0.5, 1, 1.5, 2, 3, 4, 5, and 6 months after
      fortification. In the second study, samples were analyzed one day (initial) and
      0.5, 1, 2, 3, and 6 months after fortification. For each residue and species, a
      minimum of 4 samples were analyzed by LC at each point in time, and the mean
      represented analyte concentration at the end of each time interval. Rates of
      residue depletion varied among analytes and among species. Depletion rates were
      greater in duck livers than in beef livers. Methomyl and oxamyl were depleted
      completely within 2 weeks. Between 2 and 6 months after sample fortification,
      residue depletions to levels below detection limits were observed for aldicarb,
      aldicarb sulfoxide, aldicarb sulfone, dioxacarb, promecarb, propoxur, and
      bendiocarb. The initial loss of certain carbamates during sample preparation in
      tissues exposed to room temperature for up to 8 h was greater than the subsequent
      rate of loss. Results indicate that cryogenic conditions are required for sample
      preparation and storage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8286971
TI  - Comparison of gel permeation chromatography, sweep codistillation, and Florisil
      column adsorption chromatography as sample cleanup techniques for the
      determination of organochlorine pesticide residues in animal fats.
AB  - Methods using a commercial sweep codistillation apparatus, gel permeation
      chromatography (GPC), and Florisil column adsorption chromatography were compared
      as cleanup techniques for the determination of organochlorine pesticide residues
      in animal fats by Megabore capillary gas chromatography with electron capture
      detection. Animal fat that had been previously found to contain no detectable
      organochlorine residues was spiked with 17 organochlorine pesticides at levels
      ranging from 0.1 to 0.4 mg/kg and cleaned up by each of the 3 techniques.
      Recoveries obtained for all 3 methods were in the range 73-113%, with
      coefficients of variation between 1.1 and 11.2%. Equivalence of method
      performance was further demonstrated by performing replicate analyses of beef and
      sheep fat containing naturally incurred residues of heptachlor epoxide, dieldrin,
      p,p'-DDE, p,p'-DDD and p,p'-DDT. All 3 methods offer effective cleanup and
      acceptable recovery of organochlorine pesticides in animal fat. The sweep
      codistillation method has the advantages of low solvent and reagent use,
      simultaneous cleanup of 10 samples, and rapid turnaround, although thermal
      degradation of p,p'-DDT requires monitoring and control. GPC offers a high degree
      of automation but is a relatively slow sequential sample cleanup with high
      solvent use. Florisil column adsorption chromatography is a simple, proven
      technique but requires considerable solvent and reagent and has a low potential
      for automation.

PMID- 8286972
TI  - Determination of paraquat and diquat in low-moisture food crops using silica
      column cleanup and liquid chromatography with UV detection.
AB  - A sample cleanup method was developed for the determination of paraquat (PQ) and
      diquat (DQ) in low-moisture food crops. Low-moisture commodities, such as milled
      dry navy beans, are digested in acid. PQ and DQ are isolated from the digestates
      by using a 4 g column of preconditioned silica gel. The analytes are concentrated
      and then determined by liquid chromatography with a silica analytical column,
      sodium chloride as an ion-pairing re-agent, and acetonitrile as an organic
      modifier. PD and DQ are determined simultaneously with a diode array UV
      absorbance detector. Recoveries for PQ and DQ were determined on 3 different
      fortified low-moisture crops. Fortification levels ranged from 0.01 to 0.30 ppm;
      average recoveries ranged from 47.5% (DQ) to 95.3% (PQ).

PMID- 8286973
TI  - Confirmation of identities of propylene and ethylene glycols in anchovies by
      tandem mass spectrometry.
AB  - A gas chromatographic/tandem mass spectrometric (GC/MS/MS) method has been
      developed for confirming the identity of propylene and ethylene glycols added to
      bait fish for preservation. Bait fish are occasionally illegally diverted to
      human food use. The bait fish were extracted with methanol, the extract was
      centrifuged and filtered, and the filtrate was concentrated 10-fold and then
      analyzed by GC/MS/MS. The glycols were separated chromatographically without
      derivatization or preliminary cleanup. Isobutane positive ion chemical ionization
      was used to generate the protonated molecular ion species of each glycol. Product
      ion MS/MS experiments were performed to obtain spectra to confirm the identities
      of propylene and ethylene glycols. The identities of these 2 compounds in anchovy
      extracts were successfully confirmed by this approach.

PMID- 8286974
TI  - Determination of pyrethroid residues in vegetables, fruits, grains, beans, and
      green tea leaves: applications to pyrethroid residue monitoring studies.
AB  - Determination of natural pyrethrins and 12 synthetic pyrethroids in agricultural
      products was investigated. Vegetables and fruits were extracted with acetone,
      filtered after addition of coagulating solution, partitioned into n-hexane, and
      cleaned up on a Florisil column (as necessary). Pyrethroids were determined by
      gas chromatography/electron capture detection (GC/ECD) by using a methyl silicone
      coated fused-silica capillary column, and recoveries were calculated by summing
      peak areas of the components. GC/mass spectrometry was used to identify the
      pyrethroids detected by GC/ECD monitoring. Grains and beans containing lipids
      were analyzed by extraction with acetonitrile, partition into n-hexane, Florisil
      column cleanup, and capillary GC/ECD. The coagulation method was suitable for
      nonfatty crops such as vegetables, fruits, and green tea leaves, because
      recoveries were good and Florisil column cleanup was not needed in most cases.
      The coagulation method was not applicable to lipid-containing crops such as
      grains and beans because of low recoveries. Recoveries for 18 crops at
      fortification levels of 0.25-1.0 ppm were 60.0-103.5%. No pyrethroids were
      detected from the nonfortified crops tested except green tea leaves, in which
      fluvalinate was detected at 0.89 ppm.

PMID- 8286975
TI  - Determination of formetanate hydrochloride in selected fruits by coupled-column
      cation exchange liquid chromatography.
AB  - A strong cation exchange (SCX) liquid chromatographic (LC) method is described
      for determination of formetanate hydrochloride residue in pome, citrus, and stone
      fruits. A test portion of fruit, homogenized with the peel left on, was blended
      with acidified acetonitrile and filtered. A portion of extract was finely
      filtered, and a 500 microL aliquot (ca 0.2 g test sample equivalent) was loaded
      onto an SCX solid-phase extraction (SPE) LC column, which replaced the injection
      loop of the LC injection valve. Cations were selectively enriched; noncations
      were eluted by acetonitrile in a pre-separation cleanup. Turning the valve to the
      inject position coupled the SPE column to an SCX analytical column for separation
      and detection at 250 nm. The mobile phase was 0.4M pH 3.0 ammonium phosphate
      buffer-water-acetonitrile (50 + 25 + 25). Formetanate cation was quantitated by
      peak area and regression coefficients from a 5-point linear calibration covering
      a 100-fold range. Recovery of duplicate fortifications of apple, pear, orange,
      and peach averaged 89-99% at the respective U.S. tolerances of 3, 3, 4, or 5 ppm
      and averaged 93-99% at one-tenth of the respective tolerance level. Peel pigments
      or variable peel bulk of crop varieties tested, as well as other endogenous fruit
      material, contributed interference that was below the 0.02 ppm limit of
      detection. In a 1991 limited survey comprising 15 samples, none were found
      violative. Residues were found in 2 samples, but only 1 measurement was
      quantifiable, near the 0.06 ppm limit of quantitation.

PMID- 8286976
TI  - Rapid gas chromatographic method for the multiresidue screening of fruits and
      vegetables for organochlorine and organophosphate pesticides.
AB  - A rapid and reliable method was developed for the determination of pesticides in
      fruits and vegetables. A 100 g sample is extracted with a mixture of 200 mL
      petroleum ether and 100 mL 2-propanol. The extract is backwashed 4 times, twice
      with aqueous sodium sulfate and twice with 350 mL distilled water, and then dried
      over 15 g sodium sulfate. The dried extract is analyzed by capillary gas
      chromatography with selective organochlorine and organophosphorus detection. The
      method determines primarily nonpolar pesticides, with recoveries ranging from 81
      to 114%, and has an average limit of detection of 10 ppb for both detectors.

PMID- 8286977
TI  - Inductively coupled plasma atomic emission spectrometric determination of tin in
      canned food.
AB  - Various canned foods were digested sequentially with HNO3 and HCl, diluted to 100
      mL, and filtered, and then tin was determined by inductively coupled plasma
      atomic emission spectrometry (ICP/AES). Samples of canned Satsuma mandarin,
      peach, apricot, pineapple, apple juice, mushroom, asparagus, evaporated milk,
      short-necked clam, spinach, whole tomato, meat, and salmon were evaluated. Sample
      preparations did not require time-consuming dilutions, because ICP/AES has wide
      dynamic range. The standard addition method was used to determine tin
      concentration. Accuracy of the method was tested by analyzing analytical
      standards containing tin at 2 levels (50 and 250 micrograms/g). The amounts of
      tin found for the 50 and 250 micrograms/g levels were 50.5 and 256 micrograms/g,
      respectively, and the repeatability coefficients of variation were 4.0 and 3.8%,
      respectively. Recovery of tin from 13 canned foods spiked at 2 levels (50 and 250
      micrograms/g) ranged from 93.9 to 109.4%, with a mean of 99.2%. The quantitation
      limit for tin standard solution was about 0.5 microgram/g.

PMID- 8286978
TI  - Determination of ultratrace levels of lead in infant formula by isotope dilution
      inductively coupled plasma mass spectrometry.
AB  - A simple method was developed for the accurate and precise determination of low-
      and sub-ppb (ng/g) concentrations of lead in infant formula by isotope dilution
      inductively coupled plasma mass spectrometry using ultrasonic nebulization. After
      addition of a known amount of 207Pb, samples were microwave digested and the
      ratio 207Pb/208Pb was measured in the digests. Agreement with certified values
      for lead in milk powder standard reference materials was good, and isotope
      dilution analysis using 206Pb yielded identical results for the standard
      reference materials. Lead concentrations determined for several infant
      nutritional products were verified by an independent method. Typically, relative
      standard deviations of < 4% were obtained with this method for lead
      concentrations above 2 ppb. The recovery of 2 ng of lead from an aqueous standard
      carried through the microwave digestion was 104 +/- 4%. Infant formula
      (containing 0.6 ppb lead) to which 0.4 ng of natural-abundance lead had been
      added, to simulate a formula containing 0.9 ppb lead, was analyzed by isotope
      dilution, and the result was 96 +/- 18% of the theoretical value. Thus,
      differences of 0.3 ppb lead could be clearly distinguished, and the detection
      limit was estimated to be 0.1 ng lead per gram of infant formula. The keys to
      accuracy for this method are minimizing contamination and accurately determining
      the concentration of lead in the isotopically enriched standard.

PMID- 8286979
TI  - Fluorometric determination of total and bound sulfite in wine by N-(9
      acridinyl)maleimide.
AB  - N-(9-Acridinyl)maleimide (NAM) reacts with sulfite in wine and gives strong
      fluorescent derivatives that lead to highly sensitive fluorometry of both total
      and bound sulfite in wine. Values of free and bound sulfite in wine determined by
      the NAM method and the modified Rankine method agreed. Sulfite was determined in
      < 200 microL wine within 2 h.

PMID- 8286980
TI  - Determination of sulfur dioxide in wines and beverages by flow injection analysis
      with reductive amperometric detection and electrolytic cleanup.
AB  - A new flow injection method is described for the determination of sulfur dioxide
      in red and white wines and other beverages. A dual-electrode electrochemical
      detector eliminates interferences by reduction at an upstream coulometric
      electrode before reductive detection of sulfur dioxide at the amperometric
      electrode. The data for free and total sulfur dioxide in wines and other
      beverages agree well with those obtained by the standard aspiration-oxidation
      method.

PMID- 8286981
TI  - Liquid chromatographic method for determining the percent of olestra in lipid
      samples.
AB  - A liquid chromatographic (LC) method has been developed to determine the percent
      of olestra in lipid samples. To achieve the highest degree of accuracy, this
      method requires the use of an olestra standard with the same molecular
      composition as the olestra in the lipid sample to be analyzed. Samples were
      analyzed by reversed-phase LC using an evaporative light-scattering detector.
      Chromatography was performed with a 5 microns octadecylsilane-Zorbax column that
      separates olestra from other lipophilic components. Three types of olestra
      standards (soybean-oil olestra, unheated cotton-seed-oil olestra, and heated
      cottonseed-oil olestra), each analyzed in soybean oil, showed linearity when the
      amount of olestra injected ranged from 20 to 160 micrograms (r = 0.9996). The
      area under the olestra peak (retention time 3.5 to 4.9 min) was used to quantify
      the amount of olestra in olestra-lipid samples, by comparing the olestra area for
      the sample with that of the standard using a curve derived by linear regression.
      The method was evaluated using 3 types of olestra blended with soybean oil and
      varying the percent of olestra in the olestra-lipid blend from 5 to 90%. Recovery
      of olestra from these olestra-lipid blends varied from 99.2 to 106.0%,
      demonstrating excellent accuracy, with method precision expressed as the
      coefficient of variation, 0.9%. Each error estimate was derived from 5 parallel
      determinations. With proper validation (e.g., running an olestra-free blank for
      each lipid matrix), this method provides a rapid, accurate, and precise technique
      for measuring the percent of olestra in lipids extracted from olestra-formulated
      foods and in olestra-lipid blends.

PMID- 8286982
TI  - Complement activation during saturation diving.
AB  - In this study, the levels of activated complement fragments C3a and C5a were
      measured on 11 U.S. Navy divers as they performed a 28-day saturation dive to a
      pressure equivalent of 1,000 feet of seawater (fsw, 31.3 atm abs). Two subjects
      developed symptoms consistent with the high pressure nervous syndrome (HPNS) and
      three were treated for type I DCS (joint pain only). These events allowed us to
      test two hypotheses: a) alterations in C3a or C5a levels during compression are
      related to the occurrence of HPNS and b) increases in complement fragments are an
      indicator of decompression stress associated with type I DCS. There was no
      correlation between changes in C3a and C5a levels during compression and the
      diagnosis of HPNS. Our results suggest that an increase in C3a and C5a levels
      during saturation diving correlates with decompression stress and the clinical
      diagnosis of type I DCS.

PMID- 8286983
TI  - Absence of intravascular bubble nucleation in dead rats.
AB  - Bubble formation in the inferior vena cavae (IVC) of dead rats was investigated
      after 6-15-h exposures to air at 123 atm abs (12.5 MPa) and decompression to 1
      atm abs at 13.6 atm/min (1.4 MPa/min). The maximum estimated air-supersaturation
      attained in the IVCs after decompression was 6.1-18.3 atm (0.6-1.8 MPa). Bubbles
      were detected by light microscopy, buoyancy, and underwater dissection. No
      bubbles formed in 42 blood-filled IVCs that were isolated from the circulation by
      ligatures, but bubbles were always observed in unisolated IVCs (P < 0.000005).
      Other isolated IVCs were filled with tap water, water and bubbles, or water and
      iron filings. Bubbles formed in 13% of the IVCs filled with tap water, in 16% of
      the IVCs containing water with preexisting bubbles, and in 80% of the IVCs
      containing water with iron filings. Results indicate that at the air
      supersaturations attained in the isolated IVCs a) blood is resistant to de novo
      bubble formation; b) preexisting bubbles are dissolved by compression; c) bubbles
      in water originate from preexisting gas nuclei; and d) iron filings harbor gas
      nuclei that are able to survive 122 atm (12.4 MPa) overpressures and form bubbles
      on subsequent decompression.

PMID- 8286984
TI  - Continuous pulse oximetry in the breath-hold diving women of Korea and Japan.
AB  - Arterial oxygen saturation during breath-hold diving has not previously been
      measured continuously. We devised a submersible, waterproof, backpack computer to
      continuously record heart rate, depth, and arterial oxygen saturation (SPO2) as
      determined by earlobe pulse oximetry. Our measurements showed that one assisted
      (Funado) diver had reduced SPO2 values immediately after surfacing from 22 dives
      which lasted 23-76 s, from a mean of 99 +/- 1% SPO2 to 96 +/- 3% SPO2. SPO2
      returned to 97 +/- 2% within 15 s after surfacing (P < 0.05 surface value differs
      from predive base line). Four unassisted (Cachido) divers showed no significant
      reduction of mean predive SPO2 below 98 +/- 2% at any time during the dive or
      recovery period in 92 routine dives lasting from 15 to 44 s. Upon surfacing from
      diving, mean SPO2 was 98 +/- 2% and the mean SPO2 15 s after surfacing was 97 +/-
      3% for the unassisted divers. Three Cachido divers were asked to dive and breath
      hold for as long as possible. Mean SPO2 at the conclusion of breath holding was
      73% after an average dive and breath hold lasting 69 s.

PMID- 8286985
TI  - Failure to reduce body water loss in cold-water immersion by glycerol ingestion.
AB  - The efficacy of ingesting an aqueous glycerol solution to enhance body water
      retention during prolonged cold-water dives was evaluated. Nine Naval Special
      Warfare divers performed a 3-h dive in 13 degrees C water. Divers were assigned
      to either a water-treatment group (WT) or a glycerol-treatment (GT) group. WT
      ingested 30 ml water/kg lean body mass (LBM). GT ingested a solution consisting
      of 1.2 ml glycerol/kg LBM and 30 ml water/kg LBM. Blood was drawn at
      prehydration, 90 min after hydration, and 20 min after the 3-h dive for serum
      glycerol, glucose, free fatty acids, lactate, and electrolyte determinations.
      Fluid intake and output was recorded and urine analyzed for osmolality,
      electrolytes, and specific gravity. Serum glycerol values in GT were 200 times
      greater at posthydration than prehydration and 100 times greater at postdive than
      at prehydration. Urine output, total body weight loss, and non-urine weight loss
      during posthydration and dive sampling periods were not significantly different
      between treatment groups. Hyperhydration with an aqueous glycerol solution of 1.2
      ml glycerol/kg LBM seems ineffective in significantly reducing body water loss in
      divers during prolonged cold-water immersion.

PMID- 8286987
TI  - Hyperbaric oxygen as an adjunctive treatment for severe laryngeal necrosis: a
      report of nine consecutive cases.
AB  - Laryngeal necrosis is a rare complication of therapeutic radiation, but when it
      does occur there is no established, definitive treatment and laryngectomy is
      frequently required. This report is a retrospective review of all patients
      referred for hyperbaric oxygen (HBO) therapy to a single hyperbaric medicine unit
      for treatment of their laryngeal necrosis between 1980 and 1985. Nine patients
      were in this series. One patient had had a vertical hemilaryngectomy and another
      a supraglottic laryngectomy before referral. Eight of the nine patients had a
      Chandler grade IV necrosis and the ninth had a Chandler grade III necrosis. All
      nine patients were able to maintain their voice until death or last follow up.
      Seven of the nine patients maintained good voice quality while two exhibited some
      hoarseness. All patients with tracheostomies were able to be decannulated, and
      all patients with fistulae had these closed. No untoward reactions to HBO
      occurred. Based on this review, HBO is recommended as a therapeutic option
      whenever laryngeal necrosis occurs and there is a chance to save the larynx.

PMID- 8286986
TI  - Hyperbaric hyperoxia enhances the lethal effects of amphotericin B in Leishmania
      braziliensis panamensis.
AB  - Leishmania braziliensis panamensis promastigotes were exposed in vitro to
      amphotericin B (AmB), menadione, or phenazine methosulfate under normoxic
      conditions. Promastigotes were also exposed to hyperoxia alone (100% O2 at total
      pressures of 101.3 or 253.3 kPa), or combined with drugs. After incubation for 24
      h at 27 degrees C, viable promastigotes were stained with fluorescein diacetate
      and counted using epifluorescence microscopy. Hyperbaric hyperoxia alone (PO2 =
      229.3 kPa) was as effective as AmB alone (0.2 microM); both reduced the number of
      viable promastigotes to approximately 13% of the original inoculum. In addition,
      AmB in a hyperbaric hyperoxic environment killed more promastigotes (97% of the
      original inoculum) than AmB in normoxic (PO2 = 21.1 kPa) or hyperoxic conditions
      (PO2 = 91.7 kPa). Finally, AmB in hyperbaric hyperoxia killed significantly more
      (75%) promastigotes than hyperbaric hyperoxia alone. High oxygen tensions did not
      significantly alter the lethal effects of either menadione or phenazine
      methosulfate. In conclusion, the lethal effects of low dose AmB in Leishmania
      promastigotes were augmented by hyperbaric hyperoxia in vitro, but only at oxygen
      doses too high to be tolerated by human patients.

PMID- 8286988
TI  - Hyperbaric oxygen and the cancer patient: a survey of practice patterns.
AB  - A questionnaire was sent to 179 clinical hyperbaric medicine facilities to survey
      treatment policies and referral patterns for patients with a history of
      malignancy. Eighty-five surveys were returned. Most respondents indicated that
      they would accept patients with a history of malignancy for either adjuvant or
      emergent hyperbaric oxygen (HBO). Depending on specific circumstances, from about
      one third to one half of respondents believed that such patients should be
      informed of a theoretical potential for tumor acceleration or reactivation. An
      overwhelming majority had not personally attended nor had they been told by
      colleagues of cases of patients whose malignancy had been activated or
      accelerated by HBO. A large majority felt that referring physicians did not
      believe that HBO was carcinogenic, and that referrals were not prevented by such
      concerns. Seven percent believed that HBO is potentially carcinogenic. Forty-two
      percent of respondents felt that they might be at risk for malpractice litigation
      if a patient had reactivation or acceleration of a malignancy. Among respondents
      to the questionnaire, there is a consensus that HBO does not have cancer
      promoting or accelerating properties.

PMID- 8286989
TI  - The contribution of neurophysiologic techniques to the investigation of diving
      related illness.
AB  - This review considers the important role of experimental and clinical
      neurophysiologic techniques in the investigation of diving-related illness. The
      invasive monitoring of neural function using evoked potentials has been central
      to the creation of animal models of neurologic decompression illness (DCI). Such
      models have produced important insights into the nature of DCI and have reduced
      the empiricism of treatment protocols. However, caution is required in the
      application of neurophysiologic data from animal models of the disease to human
      DCI. Conflicting evidence exists for the usefulness of electroencephalographic
      and evoked potential studies in the investigation of acute neurologic DCI in man.
      Some neurophysiologic evidence has been produced to support the contention that
      diving may cause subclinical injury to the central nervous system.

PMID- 8286990
TI  - Evaluation of a hyperbaric system to be used in conjunction with a fluorometer.
AB  - A high-pressure chamber that can be used inside the sample chamber of a
      spectrofluorometer is described and some performance characteristics are
      presented. The chamber body, constructed of 316 stainless steel, is temperature
      regulated using resistive heating elements and a microprocessor-based
      proportional integral derivative controller. The chamber holds a standard 1-cm2
      cuvette that indexes with an electromagnetic stirrer. Injection of different
      solutions into the closed and pressurized (6.8 MPa) vessel is accomplished by
      computer-controlled, low-volume solenoids attached to separate microliter
      injection ports. Repetitive injections of fluids down to a volume of 7
      microliters are possible in the pressurized chamber. Temperature stability of the
      chamber is +/- 0.2 degrees C at atmospheric or elevated pressure. However, during
      the initial phase (first 3 min) of pressurization, at a compression rate of 0.62
      MPa/min, a 0.23 degrees C/min increase in temperature occurs. The chamber windows
      depress the relative intensity of the emitted light by approximately 20% for
      visible light and 40% for near UV; however, total sensitivity of the system is
      sufficient to accomplish most determinations while maintaining a good signal-to
      noise ratio. This system can be used to evaluate the response of several
      molecular and cellular events during compression and at depth with the use of
      various fluorometric probes.

PMID- 8286991
TI  - Misusing anabolic drugs: possibilities for future policies.

PMID- 8286992
TI  - Does nicotine replacement therapy work?

PMID- 8286993
TI  - What really drives change?

PMID- 8286994
TI  - Benno Pollak Lecture 1992. Alcohol dependence--an illness with a treatment?
AB  - Unlike some countries, Britain may have experienced a rise rather than a fall in
      alcohol-related illness during a decade when consumption has not risen.
      Objections to the "illness concept" may impede our vision and the range of
      services we develop. It is possible to agree with objectors to the illness
      concept that a unidimensional view is unhelpful; that explanations are often only
      attributions; that the construct "illness" is not needed for help to be offered,
      its use could undermine self-mastery, and its misuse can breach civil rights.
      Learning can explain much over-drinking. However, the concept need not imply
      bimodality of drinkers; the syndrome of alcohol dependence has uses and does not
      imply a cause; physical and mental explanations are not incompatible; genetic and
      biochemical research has promise. Developments in treatment are still limited,
      but the mysteries of the free-will dilemma should not prevent us seeing
      physiological, psychological and social contributants as partners rather than
      rivals.

PMID- 8286995
TI  - The risk of alcohol.
AB  - We have reviewed 156 papers which provided sufficient information to relate
      individual alcohol consumption to risk for a variety of physical damage. Overall,
      there was evidence for a dose-response relationship between level of alcohol
      consumption and risk of harm for liver cirrhosis, cancers of the oropharynx,
      larynx, oesophagus, rectum (beer only), liver and breast, and blood pressure and
      stroke. An increased risk of cardiac arrhythmias, cardiomyopathy and sudden
      coronary death was associated with heavy drinking. There was evidence for a
      protective effect of alcohol consumption against risk of coronary heart disease,
      which could be achieved at consumption levels of less than 10 g alcohol a day.
      The mortality of non-drinkers was higher than that of moderate drinkers in some
      studies. Level of alcohol consumption and total mortality were dose-related when
      non-drinkers were excluded. The finding of a dose-relationship between alcohol
      and harm suggested causality. It was not possible to define individual risk for
      all harms at a given level of alcohol consumption because of variations in
      methodology, but some idea of the order of magnitude of the increased risk can be
      obtained from calculating trends of pooled log-odds ratios. At levels of alcohol
      consumption of more than 20-30 g a day, all individuals are likely to accumulate
      risk of harm. Current guidelines on upper limits of lower risk drinking in
      different countries (168-280 g of alcohol a week for men and 84-140 g a week for
      women) reflect levels at which the risk of total mortality is not greatly
      increased above one.

PMID- 8286996
TI  - Relative frequency of heavy drinking and the risk of alcohol dependence.
AB  - Data from a national representative sample of US adults were analyzed to
      determine the association between the relative frequency of heavy drinking (the
      proportion of drinking occasions on which 5+ drinks were consumed) and past-year
      alcohol dependence, adjusting for the influences of average ethanol intake and
      sociodemographic factors. Fifty-seven percent of current drinkers reported never
      drinking 5+ drinks, and 21% drank 5+ drinks at least once but on less than 10% of
      all drinking occasions. Nine percent reported drinking 5+ drinks on at least half
      of all drinking occasions. Average daily intake was positively correlated with
      the relative frequency of heavy drinking, and both consumption measures were
      positively associated with the risk of alcohol dependence. Increases in either
      relative frequency of heavy drinking or average ethanol intake reduced, but did
      not eliminate, the effect of the other on the risk of dependence. The excess risk
      of dependence associated with frequent heavy drinking varied among population
      subgroups and was increased by age, education, and female gender.

PMID- 8286997
TI  - High risk drinking settings: the association of serving and promotional practices
      with harmful drinking.
AB  - A household survey of 1160 Western Australian adults was used as a basis for
      exploring drinkers' reports about the settings in which they drank alcohol and
      their experiences of alcohol related harm. Of the 873 drinkers identified, 7.9%
      had experienced some form of acute alcohol related harm over the previous 3
      months. Violent incidents were the most common of these and drink-driving
      offences the least. Such harm was significantly more likely among drinkers who
      variously drank 'heavily', were male, single, under 25 years of age and/or who
      drank on licensed premises. Regression analyses revealed that even when
      demographic characteristics of the drinkers were controlled for licensed premises
      were significantly more likely to be the settings used prior to harm occurring.
      Bar staff continuing to serve 'obviously intoxicated' customers was the most
      powerful predictor of harm. Premises which offered discounted drinks or permitted
      crowding also tended to be those where intoxication was permitted but these
      variables were not directly associated with an increased risk of harm. These
      findings lend further weight to the view that prevention efforts should focus on
      licensed drinking environments and, in particular, the practice of continuing to
      serve obviously intoxicated customers.

PMID- 8286998
TI  - The importance of amount and location of drinking for the experience of alcohol
      related problems.
AB  - People's self report of a variety of alcohol-related problems was collected as
      part of a national survey carried out in New Zealand in 1988. These problems
      included self perception of adverse effects of drinking on a number of life areas
      such as health, friendships and financial position; items covering tangible
      consequences of alcohol use and items suggestive of alcohol dependence. The
      experience of these problems was predicted from a number of socio-demographic
      variables and respondent's reports of their typical drinking behaviour. Of the
      socio-demographic variables only age was found to relate strongly to experience
      of problems. The overall frequency of drinking relatively large amounts and the
      typical quantity drunk in certain licensed premises (hotels, taverns and clubs)
      and the typical quantity drunk in others' homes predicted the experience of
      problems. These findings are similar to research from other countries using
      different methodologies and support the likely effectiveness of prevention
      strategies which reduce the access of young people to alcohol and which aim to
      influence the amounts consumed in drinking sessions on licensed premises.

PMID- 8286999
TI  - Structure and correlates of alcohol dependence in clinical samples in the United
      States and Russia.
AB  - Using items from the Composite International Diagnostic Interview, dimensionality
      of the alcohol dependence syndrome was assessed in clinical samples in the United
      States and Russia. In both groups, a single-factor model provided a high degree
      of goodness of fit thus demonstrating cross-cultural coherence of the construct.
      The item dealing with narrowing of the drinking repertoire is most disparate in
      each sample. Severity of alcohol consequences was moderately related to alcohol
      dependence in both samples. Demographic variables, however, correlated less with
      severity of consequences. After the effects of severity of dependence and
      demographics were removed, quantity/frequency of recent alcohol consumption did
      not contribute to severity of consequences. Country, however, remained a
      significant, but small, predictor of severity of alcohol consequences.

PMID- 8287000
TI  - The effect of food deprivation on alcohol consumption in bulimic and control
      women.
AB  - The effect of food deprivation on alcohol self-administration was examined in
      five women with bulimia nervosa and five healthy controls in a semi-naturalistic
      experimental design. In this within-subjects study, each individual underwent two
      food-deprived and two non-deprived sessions. The deprivation condition consisted
      of no food or caloric beverages for 19 hours prior to the experimental procedure.
      On each of the 4 days, subjects watched a 2-hour segment of an epic movie and
      were permitted to drink ad libitum. No differences were observed in the number of
      grams of alcohol consumed under deprived and non-deprived conditions for either
      group. Breath alcohol levels were significantly higher under the non-deprived
      condition despite equivalent amounts of alcohol consumed and similar ratings of
      the subjective sense of tipsiness. Bulimic women consumed equivalent calories due
      to alcohol as control women but significantly fewer calories due to non-alcoholic
      beverages. These results do not support the hypothesis that food deprivation
      leads to increased self-administration of alcohol in women.

PMID- 8287001
TI  - Continued risk behaviour among HIV positive drug injectors in London:
      implications for intervention.
AB  - Findings are reported on the risk behaviour of 104 confirmed HIV-1 antibody
      positive drug injectors in London. Findings indicate that 41.3% of respondents
      had never received treatment or help for their drug use, and that 52.0% had never
      received a named test for HIV antibodies. The majority of confirmed HIV positive
      respondents (70.1%) were unaware of their HIV positive status. Respondents
      unaware of their HIV positive status were less likely to use condoms with primary
      sexual partners than respondents aware of their HIV status, and were marginally
      (though not significantly) more likely to report borrowing and lending used
      injecting equipment. Overall levels of risk-taking were similar to those reported
      in UK studies of injecting drug use as a whole. The paper concludes by
      emphasising the high potential for HIV transmission among the equipment sharing
      and sexual partners of HIV positive drug injectors and by stressing the
      importance of low-threshold HIV testing, education and treatment interventions in
      the community. If significant proportions of HIV positive drug injectors remain
      unaware of their antibody status, and if they also continue to engage in
      behaviours of risk to others, the spread of HIV among drug injectors and their
      partners may escape current efforts of prevention and prevalence control.

PMID- 8287002
TI  - HIV risk behaviours among female prostitute drug injectors in Glasgow.
AB  - This paper focuses upon HIV-related risk behaviours of 51 female drug injecting
      prostitutes, interviewed as part of a serial cross-sectional study of injecting
      drug users in Glasgow. Forty-five per cent injected with used needles and
      syringes in the 6 months prior to interview. Condom use in private sexual
      relations was low with only 9% of those with primary partners and 22% of those
      with casual partners reporting consistent use of condoms with these partners. In
      contrast, use of condoms for all commercial sexual encounters was almost
      universal. Prevalence of HIV was 2.2%. Despite this low prevalence, we conclude
      that the level of injecting-related and private sexual risk behaviours reported
      here requires the continuing monitoring of drug injecting prostitutes in Glasgow.

PMID- 8287003
TI  - A preliminary survey of Italian intravenous heroin users in London.
AB  - The present study analyses the phenomenon of the migration to London of Italian
      intravenous drug users. Using structured questionnaires and prevalence data it
      was estimated that a significant number of Italian intravenous drug users (at
      least 1000) were living in London at the time of the study (1990), of whom 30%
      were HIV positive. Risk-taking behaviour was disturbingly high. The reasons for
      migrating were identified, and the implications of recent Italian legislation are
      briefly discussed. The data indicated that the living conditions of these
      immigrants in London were precarious and that these vulnerable individuals had
      little access to services. As the barriers to travel within the European
      Community disappear, the public health problems represented by the migration of
      problem-drug users are likely to become more acute.

PMID- 8287004
TI  - Severity of dependence: data from the DSM-IV field trials.
AB  - The concept of a dependence syndrome with graded levels of severity was
      originally derived from work with alcoholics. The applicability and clinical
      utility of the dependence syndrome across a wider range of substances was
      examined as part of the DSM-IV field trials. When using a criterion count method
      to assess severity, it was found that persons cluster at different severity
      levels according to the drug on which they are dependent. Across all drug
      classes, severity correlated reasonably well with measures of quantity and
      frequency of use and with associated problems. The relationship between severity
      ratings and outcome was not tested, however data from other studies indicate that
      severity is only one of many factors that can influence outcome.

PMID- 8287005
TI  - 'Frontloading' ('halfing') among Glasgow drug injectors as a continuing risk
      behaviour for HIV transmission.

PMID- 8287006
TI  - Emerging worldwide trends of breast cancer incidence in the 1970s and 1980s: data
      from 23 cancer registration centres.
AB  - The aim of the study was to estimate the change in breast cancer incidence around
      the world in the last two decades, to investigate a hypothesized rise (of
      epidemic proportions) in incidence of the disease, and to assess the potential
      for its prevention. This was done by examining data from 23 registries worldwide.
      The anticipated widespread and epidemic proportions of the increases in breast
      cancer incidence were consistent with the proposed hypothesis. The results are
      discussed in these terms, and alternative actions for the prevention of the
      epidemic extent of breast cancer in the community are suggested.

PMID- 8287007
TI  - Primary prevention of malignant melanoma in the Stockholm Cancer Prevention
      Programme.
AB  - Malignant melanoma is the most rapidly increasing tumour in Sweden. Sunburns in
      childhood and adolescence are considered a major risk factor. The Stockholm
      Cancer Prevention Programme addresses strategies to establish sun awareness in
      the population of Stockholm county by using existing networks of standardized
      child health and preschool services, educational systems including schools,
      colleges of nursing sciences and preschool teaching (integration of sun awareness
      in curricula, and in a new syllabus for environmental theory), the Federation of
      Swedish Pharmacies, and media. Health education is designed for key persons in
      these organizations and the media, who in turn diffuse sun awareness via their
      respective organizations. The education programme only deals with primary
      prevention by behavioural changes in exposure to UV rays, ie excessive exposure
      to sun, and it is primarily intended to raise sun awareness. Experiences have
      shown that information diffusion was good in spite of limited staff resources.

PMID- 8287008
TI  - Changes in sun-related attitudes and behaviours, and reduced sunburn prevalence
      in a population at high risk of melanoma.
AB  - This study aimed to determine trends in exposure to sunlight in the context of a
      melanoma prevention programme by monitoring the prevalence of sunburn and sun
      related attitudes and behaviours. Telephone interviews were conducted in a
      baseline summer (December 1987 to February 1988) and two subsequent summers after
      the introduction of the SunSmart health promotion campaign. Interviewing a sample
      of 4,428 adult residents of the Australian city of Melbourne took place
      throughout summer on Monday evenings. Behavioural and sunburn data were reported
      for the previous weekend and relevant attitudinal data were collected. After
      adjusting for ambient ultraviolet radiation levels and temperature, survey month,
      age, sex and skin type, a significant reduction in sunburn was found. The crude
      proportion of sunburnt dropped from 11% to 10% to 7% over 3 years and the
      adjusted odds ratios (and 95% confidence intervals) were as follows: Year 1/Year
      2; 0.75 (CI 0.57-0.99) and Year 1/Year 3; 0.59 (CI 0.43-0.81). Substantial
      attitudinal shifts occurred over the 3 years. Hat wearing increased significantly
      each year (19%, 26%, 29%), as did sunscreen use (12%, 18%, 21%). However, the
      trends in mean proportion of body surface area covered by clothing were less
      clear cut (0.67, 0.64, 0.71). It is concluded that melanoma risk factor exposure
      of populations can change fairly rapidly and that well-conducted health promotion
      campaigns can play a part in producing such change.

PMID- 8287009
TI  - Does community-wide prevention of cardiovascular diseases influence cancer
      mortality?
AB  - The North Karelia Project, a community-based demonstration project for prevention
      of cardiovascular diseases since 1972 in Finland, was successful in reducing the
      population levels of the major cardiovascular risk factors. A net decline in risk
      factors and coronary heart disease mortality was observed in North Karelia in the
      1970s. Thereafter, the mortality from coronary heart disease has declined
      markedly in all of Finland. The aim of the study was to find out how the cancer
      mortality has changed in North Karelia during this longer follow-up period. Age
      adjusted mortality trends were calculated for the male population aged between 35
      and 64 years in the province of North Karelia, and in all of Finland for the
      period 1969-91, using the official mortality data. The trends and the changes
      were calculated using general linear model procedures. During the 20-year period,
      cancer mortality declined in North Karelia by 45.4% and in all of Finland by
      32.7% (P = 0.006 for difference). The greater decline in North Karelia occurred
      particularly in the second decade of the follow up, and lung cancer. The results
      support the hypothesis that reduction in the population levels of the
      cardiovascular risk factors lead to beneficial changes in cancer mortality rates,
      but such changes take longer time to manifest than for coronary heart disease.

PMID- 8287010
TI  - Increased mucosal antioxidant enzyme activities in chronic gastritis and benign
      gastric polyps.
AB  - Gastroscopy with gastric biopsy was performed in 109 individuals aged 25-71
      years. Activities of three antioxidant enzymes were assayed in biopsy specimens:
      Cu/Zn superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH
      Px). Patients were classified according to the endoscopic and histological
      findings in the following groups: normal findings (N), superficial gastritis
      (SG), mild (MAG) and severe (SAG) atrophic gastritis, gastritis after partial
      gastrectomy (PGG), hyperplastic polyp (HP), and gastric adenoma (A). Compared
      with the N group, increased activity of SOD was found in groups SG (+37%), PGG
      (+67%) and A (+35%), increased CAT activity in PGG (+40%), and increased GSH-Px
      activity in groups SG (+57%), SAG (+46%), PGG (+185%), HP (+50%) and A (+50%).
      Increased activity of antioxidant enzymes could be induced by higher
      concentrations of superoxide anion radicals, hydrogen peroxide and lipid
      peroxides, produced by phagocytic leucocytes or by polyunsaturated fatty acid in
      cellular membranes of gastric mucosa. The relation of reactive oxygen species to
      the induction of precancerous conditions and to carcinogenesis of the stomach
      requires further study.

PMID- 8287011
TI  - The psychological consequences of being at risk of developing breast cancer.
AB  - Recently the hereditary nature of some breast cancers has received a considerable
      amount of publicity. Consequently many more women today recognize that their
      family history places them at an increased risk of developing breast cancer. One
      justification for informing women that they may have a predisposition to breast
      cancer is to ensure that individuals at increased risk undergo regular screening.
      However, evidence suggests that women with a family history of breast cancer are
      no more likely to use available screening than those without such a family
      history. There is some evidence that a significant minority of these women at
      risk may be psychologically distressed to a degree that would warrant
      professional counselling. Research is needed to assess the psychological impact
      of being identified as at risk of developing breast cancer due to family history
      and to establish what can be done to reduce psychological morbidity in these
      women. In view of the advances being made generally in molecular biology, with
      the identification of genetic markers for different diseases being announced
      regularly, such psychosocial research is overdue and imperative.

PMID- 8287012
TI  - A reappraisal of W.R.D. Fairbairn.
AB  - W.R.D. Fairbairn was a noted Scottish psychoanalyst who helped launch the "object
      relations revolution." While working within the traditional Freudian and Kleinian
      framework, he developed ideas of importance that have hitherto been eclipsed but
      that are now resurfacing, thanks to current awareness of primitive mental
      disorders, child abuse, and infant development research. Fundamentally, he
      challenged the primacy of the drives and the pleasure principle and stated that
      the infant is object-seeking from the beginning. Furthermore, he established the
      dissociative nature of the schizoid personality in particular and the schizoid
      aspects of all psychopathology in general. The author summarizes Fairbairn's work
      from historical, theoretical, and clinical perspectives.

PMID- 8287013
TI  - An intersubjective view of the therapeutic process.
AB  - The author presents an intersubjective view of the therapeutic process,
      emphasizing the investigative and interpretive tracking of the figure-ground
      relationships among the various dimensions of the transference as they take form
      within the analyst-patient system. The author proposes that a crucial ingredient
      of the therapeutic action of psychoanalytic interpretations can be found in their
      specific transference meanings for the patient.

PMID- 8287014
TI  - Marital satisfaction in the lives of physicians.
AB  - Marital satisfaction data from a large sample of physicians and their spouses and
      dentists and their spouses suggest that about 85% of professionals and spouses
      are satisfied with their marriages. High levels of marital satisfaction are
      associated with high work satisfaction, low work stress, and fewer psychiatric
      symptoms. These findings do not support the widely held belief that physicians'
      marriages are more apt to be dysfunctional than those of other persons. The
      authors discuss this difference from two perspectives: (1) sampling differences
      and (2) differences between marital assessments from inside and outside the
      marriage.

PMID- 8287015
TI  - Combat and personality change.
AB  - In response to combat, some soldiers develop a feeling of satisfaction in
      killing. The authors label this reaction the "heart of darkness experience,"
      after the story by Joseph Conrad (1903/1982). They describe their clinical
      experience of seeing this response as part of a spectrum of reactions ranging
      from no personality change to rather gross personality change. After exploring
      psychological factors involved in this change, they suggest relevant treatment
      considerations.

PMID- 8287016
TI  - Combat stress reactions in Iraqi enemy prisoners of war.
AB  - Combat stress reactions (CSR) are a source of significant morbidity on the
      battlefield, and they initiate the cascade of psychophysiological dysfunction
      that results in the posttraumatic stress disorders. During Operation Desert Storm
      in early 1991, very few allied CSR casualties were observed. However, Iraqi
      soldiers experienced intense conditions likely to result in CSR. Using
      semistructured interviews, the authors examined Iraqi enemy prisoners of war for
      the presence of CSR and compared their responses to two groups of U.S. soldiers.
      Iraqi prisoners of war experienced many CSR symptoms that reduced their
      functional capacity during combat, but they had few residual symptoms.

PMID- 8287017
TI  - Stage fright in musicians: a psychodynamic perspective.
AB  - Stage fright is a mystifying and unnerving experience for many performing
      musicians, and it often impedes professional and personal fulfillment in careers.
      However, when some performers seek psychological treatment, it is not unusual for
      them to wish for a quick cure for a problem that is complex and overdetermined.
      Using psychoanalytic theory and a case example, the author illustrates how stage
      fright is related to an individual's life history and how its symptoms are the
      manifestation of complex unconscious processes. Questions are raised about
      problems that arise in treating performers.

PMID- 8287018
TI  - Nutrition and psychotherapy: collaborative treatment of patients with eating
      disorders.
AB  - The nutritionist has a variety of roles in the treatment of patients with eating
      disorders. The authors describe the psychotherapeutic issues raised in the course
      of this work. They also discuss how to integrate the nutritionist most
      effectively into a multidisciplinary team, and in particular how to build a
      collaborative relationship with the psychotherapist in creating and implementing
      a cohesive treatment plan.

PMID- 8287019
TI  - Psychiatric treatment of Roman Catholic religious patients: a pilot follow-up
      study.
AB  - The pilot follow-up study reported here was undertaken to determine the treatment
      outcome of Roman Catholic religious priests, sisters, and brothers treated at The
      Menninger Clinic during a 10-year period. The authors stress the importance of
      involvement by the religious community in treatment and follow-up, and of
      opportunities in treatment to address spiritual and vocational issues. The
      extremely low response rate requires that the findings be regarded as tentative
      and as a pilot study for further research. However, the data do suggest some
      general conclusions for treatment of this population.

PMID- 8287020
TI  - Proverb familiarity and the mental status examination.
AB  - Asking patients to interpret proverbs is a traditional method of assessing
      abstract thinking ability. Familiarity with a proverb increases the likelihood of
      interpreting it correctly. Differences in proverb familiarity among patients
      could lead clinicians to incorrectly conclude that a patient is thinking
      concretely, and thus to underestimate the patient's cognitive ability. Clinicians
      should be aware of this possibility when assessing patients from different racial
      and gender groups. The authors surveyed 229 Afro-American and 104 Caucasian high
      school students to determine their familiarity with 25 proverbs. Thirty-seven
      clinicians were also asked to rate their patients' familiarity with the same
      proverbs. The authors found no differences in proverb familiarity between the
      black and white students or the male and female students. Clinicians' beliefs
      about proverb familiarity in their patients were found to be inaccurate.

PMID- 8287021
TI  - Multidrug resistance and behavioural phenotype of cancer cells.
AB  - Resistance to cytotoxic chemotherapy is a major obstacle preventing successful
      treatment of cancer, allowing dissemination of tumour metastases, and may be
      viewed as the ultimate cause of death in the majority of patients with a
      malignant disease. Although cytotoxic chemotherapy is classically employed to
      produce maximal killing of malignant cells, the therapeutic doses of individual
      drugs required to achieve this objective are, in general, highly toxic to non
      neoplastic host tissues. However, there are several different aspects of cancer
      cell biology, distinct from their susceptibility to cytotoxicity, that might be
      exploited in order to alter the behavioral phenotypes of malignant neoplasms.
      Such features include regulation of cell proliferation, tumorigenicity and
      metastatic potential. Non-cytotoxic modulation of malignant cells may provide an
      alternative, and more effective, method of controlling the aggressive behaviour
      of cancer cells while exhibiting less iatrogenic morbidity and mortality than the
      therapeutic regimens presently employed.

PMID- 8287022
TI  - Subcellular localization and antiviral activity of carminic acid/poly r(A-U)
      combinations.
AB  - Carminic acid (CAR) enhances the antiviral activity of poly r(A-U) twelve-fold
      without increasing interferon induction, inactivating the vesicular stomatitis
      virus or inducing host cell cytotoxicity. Phase contrast photomicrographs of
      human foreskin fibroblasts (HSF) incubated with CAR alone, poly r(A-U) alone or
      with a CAR/poly r(A-U) combination illustrate that the CAR/poly r(A-U)
      combinations display altered subcellular distribution with the CAR being
      localized in the nucleoli and chromatin. Phase contrast and fluorescence
      photomicrographs of adriamycin (ADR)-treated and ADR/poly r(A-U)-treated HSF
      cells corroborate these findings. These results suggest that modulation of one or
      more nucleolar processes may be responsible for the enhanced antiviral activity.

PMID- 8287023
TI  - Hemolytic function of opsonizing proteins of earthworm's coelomic fluid.
AB  - Synthetic 2-hydroxyethylmethacrylate copolymer particles (HEMA) can be opsonized
      in the coelomic fluid of Eisenia foetida earthworms. The incomplete coelomic
      fluid (i.e., the coelomic fluid after incubation with HEMA particles) exerts a
      lower level of hemolytic activity compared to complete coelomic fluid. The
      decreased hemolysis can be compensated by the addition of isolated opsonins. On
      the other hand, isolated opsonins do not possess direct hemolytic capacity. It
      can be suggested that at least one of the isolated opsonins is involved in the
      hemolytic process. These results support the hypothesized cooperation of humoral
      and cellular mechanisms in earthworm defence.

PMID- 8287024
TI  - Failure of sister chromatid separation leads to formation of diplochromosomes in
      colcemid treated PtK1 cells.
AB  - The origin of diplochromosomes has been traced in multinucleate rat kangaroo
      cells (PtK1) obtained after colcemid treatment. In these cells the
      diplochromosomes were shown to originate from restitution nuclei, indicating that
      they were formed due to the omission or failure of sister chromatid separation
      and not due to endoreduplication. In this context the mechanism of sister
      chromatid separation has been discussed. The independence of this mitotic event
      from other associated processes, such as chromosome condensation, nuclear
      envelope breakdown or spindle formation has been stressed.

PMID- 8287025
TI  - Failure of centromere separation leads to formation of diplochromosomes in next
      mitosis in okadaic acid treated HeLa cells.
AB  - High concentrations of okadaic acid, sufficient to inhibit phosphatase 1 and 2A
      activities, induces formation of diplochromosomes in HeLa cells. It has been
      shown that this is due to a failure of sister chromatid separation in earlier
      mitosis in the presence of okadaic acid in the medium and not due to bypassing of
      mitosis (endoreduplication). Moreover, it has been demonstrated that the sister
      chromatid adherence does not depend on any under-replicated chromatin segment
      shared by the sister chromatids which might happen in okadaic acid induced
      premature mitosis, but due to the failure of the centromeres to separate at
      metaphase-anaphase transition. The role of phosphatase 1 in sister chromatid
      separation has been discussed.

PMID- 8287026
TI  - Modulation of glycolysis induction in primary cultures of rabbit kidney proximal
      tubule cells: the role of shaking, glucose and insulin.
AB  - We have assessed the impact of increasing oxygen availability on cellular
      phenotype expression of rabbit proximal tubule cells in primary culture developed
      with variable glucose and/or insulin contents. To mitigate hypoxia at the
      cell/medium interface, cells were shaken for the whole culture duration and their
      expressed phenotype was compared with those expressed by static cultures. O2 and
      CO2 tensions were kept constant in the incubator atmosphere. Glycolysis and
      gluconeogenesis pathways, detoxication system, and mitochondrial, apical and
      basolateral membrane marker enzyme activities were assessed. This study showed
      that the induction of glycolysis which appear in primary cultures of proximal
      tubule cells may be partially prevented by continuously shaking the cultures.
      This effect was more marked in the presence of glucose, suggesting better
      substrate oxidation in shaken cultures.

PMID- 8287027
TI  - Thapsigargin, a Ca(2+)-ATPase inhibitor, depletes the intracellular Ca2+ pool and
      induces apoptosis in human hepatoma cells.

PMID- 8287028
TI  - Sex hormone-related control of hepatic epoxide hydrolase activities in mice.
AB  - Sex-related differences in hepatic epoxide hydrolase (EH) activities towards 7
      (2',3'-epoxy)propoxycoumarin (7-glycidoxycoumarin, GOC) were investigated, mainly
      in mice but also in rats. Hepatic subcellular EH activities in the ddY mouse were
      higher in microsomes than in the soluble and mitochondrial fractions and sex
      related differences were noted in all the subcellular fractions where males had
      significantly higher activities than females. Sex differences in the hepatic
      microsomal and soluble activities similar to those in the ddY strain were also
      observed in two other strains of mice, A/J and C3H/He, and in Wistar rats. In the
      ddY strain, castration of the males caused decreases in microsomal and soluble EH
      activities, while no alteration in the activities in those fractions was found
      following castration of females. Treatment of the male castrates with
      testosterone led to recovery of the activities in microsomal and soluble
      fractions while hormone treatment of female castrates caused a rise only in
      microsomal activity. Estradiol treatments of both sexes did not cause any changes
      in the hepatic subcellular activities. In intact ddY mice, testosterone treatment
      did not affect the male microsomal and soluble EH activities, but resulted in
      stimulation of both subcellular enzyme activities in females. In contrast,
      estradiol treatment showed a suppressive effect on both subcellular activities in
      males, but had no effect on female activities. These results show that hepatic EH
      activities towards GOC are mainly under androgenic stimulatory control in mice.

PMID- 8287029
TI  - In vitro metabolic formation of a new metabolite, 6 beta-hydroxymethyl-delta 9
      tetrahydrocannabinol from cannabidiol through an epoxide intermediate and its
      pharmacological effects on mice.
AB  - The oxidative metabolism of cannabidiol (CBD) at the 8,9-double bond was
      examined. 8R,9-Epoxy-CBD was identified by GC-MS as a new metabolite of CBD
      produced by hepatic microsomal fractions of guinea pigs, rats and mice. The
      reaction required NADPH as a cofactor and molecular oxygen. The optimal pH for
      the reaction was 7.4-8.0. The 8R,9-epoxy-CBD forming activity was highest in
      guinea pigs, followed by mice and rats in the presence of 3,3,3-trichloropropene
      1,2-oxide (TCPO), an inhibitor of epoxide hydrolase. The activity was
      significantly suppressed by SKF 525-A, alpha-naphthoflavone, metyrapone and
      carbon monoxide. 8R,9-Epoxy-CBD was further converted to 6 beta-hydroxymethyl
      delta 9-tetrahydrocannabinol (6 beta-CH2OH-delta 9-TCH) and 8,9-dihydro-8,9
      dihydroxy-CBD by hepatic microsomes of guinea pigs, rats and mice. Microsomal
      formation of 6 beta-CH2OH-delta 9-THC was markedly increased in the presence of
      TCPO with a concomitant decrease in the formation of 8,9-dihydro-8,9-dihydroxy
      CBD in all animal species examined. Furthermore, 6 beta-CH2OH-delta 9-THC was
      also identified as a new metabolite of CBD produced by hepatic microsomes of
      guinea pigs. 6 beta-CH2OH-delta 9-THC exhibited THC-like pharmacological effects,
      catalepsy, analgesia, pentobarbital-induced sleep prolongation and hypothermia in
      mice, although these effects were less marked than those of delta 9-THC. This
      study presents the first example of the biotransformation of CBD to a delta 9-THC
      derivative which exhibits some pharmacological effects.

PMID- 8287030
TI  - Cytotoxicity of platinum(IV) and platinum(II) complexes containing 1R,2R
      cyclohexanediamine as a ligand.
AB  - Several Pt(IV) and Pt(II) complexes containing 1R,2R-cyclohexanediamine (1R,2R
      dach) as a carrier ligand were synthesized. The cytotoxicities and the uptake of
      the platinum complexes by leukemia L1210 cells were compared in order to study
      the correlation between their structures and cytotoxicities. [Pt(II)Cl2(1R,2R
      dach)], [(Pt(II)(oxalato)(1R,2R-dach)], and [Pt(II)(malonato)(1R,2R-dach)], which
      have excellent anticancer properties, exhibited very high cytotoxicities and were
      easily taken up by leukemia L1210 cells. [Pt(IV)Cl4(1R,2R-dach)], trans(Cl)
      [Pt(IV)Cl2(oxalato)(1R,2R-dach)], and trans(Cl)-[Pt(IV)Cl2(malonato)(1R,2R-dach)]
      also had high cytotoxicities. After a short incubation time, the uptake of
      [Pt(II)Cl2(1R,2R-dach)], [Pt(II)(oxalato)(1R,2R-dach)], and
      [Pt(II)(malonato)(1R,2R-dach)] by leukemia L1210 cells were respectively very
      similar to those of [Pt(IV)Cl4(1R,2R-dach)], trans(Cl)-[Pt(IV)Cl2(oxalato)(1R,2R
      dach)], and trans(Cl)-[Pt(IV)Cl2(malonato)(1R,2R-dach)]. In addition, trans(OH)
      [Pt(IV)(OH)2Y2(1R,2R-dach)] (Y2: oxalato or malonato) did not exhibit
      cytotoxicity towards leukemia L1210 cells, whereas trans(Cl)-[Pt(IV)Cl2Y2(1R,2R
      dach)] (Y2: oxalato or malonato) were highly cytotoxic. The accumulation of
      trans(OH)-[Pt(IV)(OH)2Y2(1R,2R-dach)] in leukemia L1210 cells was much lower than
      that of trans(Cl)-[Pt(IV)Cl2Y2(1R,2R-dach)]. Platinum(IV) complexes, in which
      leaving groups are replaced by hydroxide groups, have decreased cytotoxic
      activity, because the hydroxide groups of the platinum(IV) complex reduce the
      uptake of platinum by the cells. trans(OH),cis(Cl)-[Pt(IV)(OH)2Cl2(1R,2R-dach)],
      which has hydroxide and chloride groups, was easily incorporated into the cells
      and exhibited the high cytotoxic activity. This behavior indicates that the
      chloride group apparently overcomes the ameliorating effect of the hydroxide
      group.

PMID- 8287031
TI  - Dose-dependent hepatic handling of l-propranolol determined by multiple indicator
      dilution method: influence of tissue binding of l-propranolol on its hepatic
      elimination.
AB  - Concentration-dependency in the hepatic elimination of l-propranolol (l-PR) was
      investigated over a wide range of concentrations from 60 to 2200 microM in an
      isolated rat liver perfusion system. Under the steady-state condition produced by
      unlabeled l-PR at various concentrations, 3H-l-PR and 14C-inulin were bolusly
      injected into the portal vein, and the outflow was collected at 0.5 s intervals
      over 30 s. Up to 300 microM, the instantaneous hepatic availability of l-PR was
      approximately 4%, while it abruptly increased when the perfusate concentration
      exceeded 300 microM. To determine which process (influx or efflux or
      sequestration process) caused the nonlinearity, we calculated the rate constants
      k1 (influx), k2 (efflux), and k3 (sequestration) based on the "distributed"
      model. With increasing l-PR concentration in the perfusate, k2 increased
      approximately two times, whereas k3 decreased to approximately one-half. In
      contrast, k1 was independent of the perfusate concentration. The concentration
      dependency of k2 was explained by saturation of l-PR tissue binding, since the
      tissue unbound fraction of l-PR obtained with liver homogenates and isolated
      hepatocytes increased approximately two times. The efflux and sequestration
      clearances were then normalized by the unbound fractions in the liver. The efflux
      clearance for unbound l-PR was constant irrespective of the perfusate
      concentration, whereas the sequestration clearance for unbound l-PR (CL(int)
      showed Michaelis-Menten type saturation (Km = 28 microM, Vmax = 2.8 mumol/min/g
      liver, alpha (nonspecific) = 2- ml/min/g liver).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287032
TI  - Pharmacokinetic analysis of phenytoin and its derivatives in plasma and brain in
      rats.
AB  - The derivatives of phenytoin (DPH) were synthesized by the reaction at 3 position
      of hydantoin ring with valproic acid and valeric acid, producing valproyl DPH
      (VPDPH) and valeroyl DPH (VADPH), respectively. These derivatives showed much
      higher lipid solubilities than that of DPH. Their distribution and elimination
      were compared to those of DPH. Additionally, the concentration profiles of the
      drugs in brain and plasma were analyzed with a modified 2-compartment model. DPH
      and its derivatives, without hydrolysis to DPH in blood, were found rapidly
      distributed into brain, although the distribution of derivatives was much less,
      probably due to the high protein binding capacities. The distribution of DPH and
      its derivatives into brain regions was similar to that into the cortex cerebri.
      VPDPH and VADPH were more rapidly eliminated from plasma and brain than DPH,
      giving smaller mean residence time (MRT) values (0.92 and 0.85 h) and much
      smaller cortex/plasma concentration ratio than those of DPH. The VPDPH and VADPH
      concentrations in the cerebrospinal fluid (CSF) were also much lower than that of
      DPH. The time course of plasma and brain concentrations of DPH and its
      derivatives after i.v. administration was successfully described by the modified
      2-compartment models presented.

PMID- 8287033
TI  - Dose-dependent uptake of radioactivity by liver parenchymal and non-parenchymal
      cells after intravenous administration of fractionated 3H-heparin to rats.
AB  - The dose-dependent uptake of fractionated 3H-heparin in the subpopulations of
      liver cells, parenchymal and non-parenchymal cells, was characterized in rats in
      vivo. Following the intravenous administration of fractionated 3H-heparin, the
      radioactivity in plasma was eliminated according to the first order kinetics at
      each dose. However, the elimination rate constant decreased with dose over the
      dose range of 0.3 to 100 U/kg, suggesting nonlinear elimination. In accordance
      with the delay in the plasma elimination, the uptake rate constant of
      radioactivity by parenchymal as well as non-parenchymal cells of liver, the major
      distribution organ, also decreased. Although heparin has long been considered to
      be taken up by a reticuloendothelial system (RES) such as non-parenchymal cells
      in the liver, the uptake of fractionated 3H-heparin by parenchymal cells was
      found to be comparable with that by non-parenchymal cells at the lowest dose of
      0.3 U/kg, and even larger than that by non-parenchymal cells at the highest dose
      of 100 U/kg. The uptake clearances of fractionated 3H-heparin at the dose of 0.3
      U/kg were 86.4 and 504 ml/10(8) cells/d, respectively, for parenchymal and non
      parenchymal cells. These values were much larger than those reported for
      polyvinylpyrrolidone, which has been suggested to be taken up by fluid phase
      endocytosis. Thus, the present study revealed the significant contribution of
      parenchymal cells in the hepatic uptake of fractionated 3H-heparin. The dose
      dependent uptake with high clearance values in both parenchymal and non
      parenchymal cells provides an in vivo suggestion of the specialized transport of
      fractionated heparin in these two subpopulations of liver cells.

PMID- 8287034
TI  - Macromolecule-macromolecule interaction in drug distribution. III. Kinetic
      characterization of the uptake of fractionated [3H]heparin and the effect of
      plasma proteins in the perfused rat liver.
AB  - The concentration-dependent hepatic uptake of fractionated [3H]heparin, a
      macromolecular model drug, was kinetically characterized and the effect of plasma
      proteins, albumin and alpha-globulin, was evaluated in the perfused rat liver as
      part of an ongoing effort to elucidate the mechanism of interaction of
      macromolecular drugs with biological macromolecules and the role of this
      interaction in the drugs' distribution. In the absence of proteins, the uptake of
      fractionated [3H]heparin was saturable with the maximum uptake velocity (Vmax) of
      7.6 pmol/min/g liver and the Michaelis constant (Km) of 32.2 nM, suggesting the
      involvement of a specialized transport. alpha-Globulin (8.0 mg/ml) reduced the
      uptake of fractionated [3H]heparin at lower heparin at lower heparin
      concentrations. However, albumin (40 mg/ml) did not affect the uptake of
      fractionated [3H]heparin, suggesting an insignificant interaction. Assuming that
      fractionated [3H]heparin bound to alpha-globulin cannot be uptaken and that the
      reduction in uptake was solely attributable to the saturable Scatchard-type
      binding of fractionated [3H]heparin to alpha-globulin, the dissociation constant
      (Kd) and the binding capacity (n) were estimated to be 2.1 nM and 0.002,
      respectively. In in vitro binding experiments by ultrafiltration, Kd and n were
      estimated as 168 nM and 0.5, respectively, for alpha-globulin and 1021 nM and
      0.02, respectively, for albumin, suggesting lower affinity and higher capacity in
      vitro for each protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287035
TI  - Rat selection test with respect to laxative activity induced by barbaloin.
AB  - As individual differences in sensitivity in the laxative activity of barbaloin
      were observed in rats, a selection test for barbaloin (31.1 mg/kg, p.o.) was
      carried out between 1989 and 1991. The annual percentages of rats exhibiting a
      reaction positive to barbaloin were almost constant (about 57%). We propose that
      rats positive to barbaloin should be selected for studies on the laxative effect
      of barbaloin.

PMID- 8287036
TI  - Formation of p-hydroxycocaine from cocaine by hepatic microsomes of animals and
      its pharmacological effects in mice.
AB  - The hepatic microsomal metabolism of cocaine and the pharmacological effects of
      some metabolites were studied in experimental animals. Hepatic microsomes from
      mice, rats and guinea pigs catalyzed the oxidation of cocaine to m- and p
      hydroxycocaines. Only trace amounts of m-hydroxycocaine were detected in the
      extract of the incubation mixture with rabbit hepatic microsomes. The total
      amount of the two hydroxycocaines was less than 12% that of norcocaine which was
      the most predominant microsomal metabolite in all the animals species examined.
      The administration of p-hydroxycocaine (20 mg/kg i.p.) to mice significantly
      increased locomotor activity (total distance and number of rearing movements).
      The effect of p-hydroxycocaine was more active or comparable with that of
      cocaine, indicating that this metabolite is an active metabolite of cocaine.

PMID- 8287037
TI  - Utilization of intravenously infused maltooligosaccharides in rabbits.
AB  - The utilization of intravenously infused maltotriose, maltotetraose and
      maltopentaose was investigated in rabbits. Rabbits were infused with isotonic
      solutions of each maltooligosaccharide for 2 h and the utilization was assessed
      by the 24-h urinary loss of carbohydrates. The utilization of these
      maltooligosaccharides was good (> or = 87.5%) at a rate of 1 ml/kg/h (< or = 250
      mg/kg/h) and poor (< or = 36.2%) at a rate of 5 ml/kg/h (> 250 mg/kg/h).
      Furthermore, these maltooligosaccharides infused as 5% solution showed good
      utilization (> or = 86.2%) at a rate of 5 ml/kg/h (250 mg/kg/h). These results
      suggest the existence of a threshold dose in the utilization of intravenously
      infused maltooligosaccharides, and this threshold value in rabbits is estimated
      to be nearly 250 mg/kg/h.

PMID- 8287038
TI  - Expression of interleukin 1 family mRNAs by a highly branched (1-->3)-beta-D
      glucan, OL-2.
AB  - OL-2, a highly branched (1-->3)-beta-D-glucan, is an antitumor glucan showing
      strong hematopoietic activity with weaker adjuvant activity than schizophyllan
      (SPG), also an antitumor glucan and one which is clinically used. This paper
      deals with the gene expression of the interleukin 1 (IL-1) family in mice by OL-2
      and SPG in order to characterize the immunopharmacological activity. Gene
      expression was examined by reverse transcriptase-polymerase chain reaction
      method. Intraperitoneal administration of OL-2 (250 micrograms/mouse) expressed
      all three genes of IL-1 alpha, beta, and IL-1 receptor antagonist (IL-1ra) in the
      peritoneal exudate cells, while SPG induced a strength of IL-1 alpha mRNA
      comparable to that by OL-2 but a weaker level of IL-1 beta mRNA. SPG did not
      induce IL-1ra. Similar patterns were seen in spleen and liver by OL-2 or SPG
      administration. These findings suggest that the immunopharmacological
      characteristics of (1-->3)-beta-D-glucan are regulated under the gene expression
      of the IL-1 family.

PMID- 8287039
TI  - Direct determination of opium alkaloid-bovine serum albumin conjugate by matrix
      assisted laser desorption/ionization mass spectrometry.
AB  - Opium alkaloids (thebaine, codeine and morphine) have been conjugated with bovine
      serum albumin (BSA) to give individual antigen conjugates which are analyzed by
      matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. It became
      clear that 9 molecules of thebaine were contained in a thebaine-BSA conjugate.
      Codeine and morphine contents in individual conjugates were determined to be 12
      and 6 molecules, respectively.

PMID- 8287040
TI  - Effect of 12-O-tetradecanoylphorbol-13-acetate on expression of cell surface
      antigens in two subclones of human leukemia K562 cells.
AB  - Two subclones (K562-L and -H) were previously isolated from K562 human leukemic
      cells according to hemoglobin production: K562-L was expressed in less than 5%
      and K562-H in more than 90% of dianisidine positive cells. 12-O
      Tetradecanoylphorbol-13- acetate (TPA) suppressed the expression of the
      erythrocytic (glycophorin A) and myelocytic (CD11b) antigens in K562-L, but
      increased the expression of these antigens in K562-H. TPA increased the
      megakaryocytic (CD61) antigens in both cells. These findings suggest that there
      are distinct TPA responsible factors in K562-L and -H on the expression of the
      erythrocytic and myelocytic antigens.

PMID- 8287041
TI  - Inter-individual differences of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1
      piperidinyl]butyric acid ((+)-MPPB) disposition in rats.
AB  - Inter-individual differences of drug plasma concentration were recognized in male
      Sprague-Dawley (SD) rats after a p.o. or i.v. administration of (+)-MPPB. Rats
      could be divided into two phenotypes, the rapid-metabolizing group (RM) and the
      slow-metabolizing group (SM). The hepatic clearance (CLliver) of RM was about 10
      times larger than that of SM. Outbred SD(male, female), and Wistar(male) rats
      were mixtures of RM and SM. On the other hand, all inbred Lewis(male) rats were
      RM, and all inbred F344(male) and ACl(male) rats were SM.

PMID- 8287042
TI  - Capillary-zone electrophoretic analyses of the proteins and amino acid components
      in cerebrospinal fluid of central nervous system diseases.
AB  - Analysis systems for protein and amino acid components in cerebrospinal fluid
      (CSF) from patients with a variety of central nervous system (CNS) diseases were
      established employing capillary-zone electrophoresis (CZE). Under the conditions
      employed, the major proteins in CSF and the concurrent sera were separated into
      several respective fractions, and in the obtained electropherograms of serum
      proteins, the % values of areas of each major protein fraction (from gamma
      globulin to albumin) were in close accord with those in the densitograms of
      stained protein bands after electrophoresis on cellulose-acetate strips which had
      been done as a routine laboratory test in the hospital. Some unusual migration
      patterns of major proteins were observed in various CNS diseases, and an increase
      of glutamine in hepatic encephalitis was also detected on the electropherograms.
      A peak responsible for a minor protein component with the molecular weight of
      10000--30000, which was tentatively identified as beta-trace protein, was found
      to be contained in all the CSF samples examined, and its concentration levels
      were higher in some patients with cerebral infarction and multiple sclerosis.
      These results suggest that CZE can become a powerful aid in analyses of the
      protein and amino acid components in CSF for biochemical diagnosis of CNS
      diseases.

PMID- 8287043
TI  - Inhibition of DNA synthesis in Meth A cells by chlorpromazine.
AB  - We examined the influence of chlorpromazine, a phenothiazine derivative, on DNA
      synthesis in Meth A cells. Pulse-labelling experiments with [3H]thymidine showed
      that chlorpromazine inhibited DNA synthesis in cells cultured in vitro. The drug
      also inhibited DNA synthesis in isolated nuclei. Observation by fluorescence
      microscopy of fibroblastic cells stained with chlorpromazine indicated that the
      drug was localized in the cytoplasm and nuclear membranes, suggesting that it
      inhibited DNA synthesis in a manner dependent on the interaction of replication
      proteins with nuclear membranes. Meth A sarcomas growing in the endoderm of
      BALB/c mice regressed on intra-tumor injection of chlorpromazine, indicating that
      the drug has an anticancer action.

PMID- 8287044
TI  - Characterization of lignoceroyl-CoA ligase activity in chicken liver microsomes.
AB  - Lignoceroyl-coenzyme A (CoA) ligase activity was detected in microsomal fractions
      from chicken liver in the presence of alpha-cyclodextrin as a solubilizing agent
      of lignoceric acid. Heptakis(2,6-di-O-methyl)-beta-cyclodextrin (dimethyl-beta
      cyclodextrin) and hexakis(2,6-di-O-methyl)-alpha-cyclodextrin (dimethyl-alpha
      cyclodextrin), among the cyclodextrins tested, were more effective than alpha
      cyclodextrin as solubilizing agents. We have characterized lignoceroyl-CoA ligase
      activity in comparison with palmitoyl-CoA ligase activity. Lignoceroyl-CoA and
      palmitoyl-CoA ligase activities showed a similar dependency on CoA concentration.
      However, lignoceroyl-CoA ligase activity exhibited responses to the Mg2+ ion,
      adenosine triphosphate (ATP), ATP analogues (adenosine monophosphate (AMP) and
      adenosine diphosphate (ADP)), and heat treatment, which were distinctly different
      from the responses of palmitoyl-CoA ligase activity. These results are consistent
      with the idea that lignoceroyl-CoA and palmitoyl-CoA are synthesized by two
      different enzymes.

PMID- 8287045
TI  - Modification of liposomes by addition of HCO60. I. Targeting of liposomes to
      liver by addition of HCO60 to liposomes.
AB  - The influence of HCO60 on the blood clearance and tissue distribution of soybean
      phosphatidylcholine (PC) liposomes, encapsulating alpha-tocopherol as a marker,
      was studied in rats. The liposomes were prepared by the hydration method from a
      lipid film containing different amounts of HCO60, and by extrusion through a 0.1
      micron polycarbonate membrane filter. The blood clearance and liver uptake of
      alpha-tocopherol after i.v. administration increased with increasing the amount
      of HCO60 the liposome contained. With 80 wt% HCO60 liposomes, the accumulation of
      alpha-tocopherol in the liver was approximately three-fold that of the 100% PC
      liposomes. The uptake by lungs, spleen and kidneys did not change with the
      addition of HCO60. The findings obtained in a gel-filtration study suggested that
      alpha-tocopherol is not removed from the liposomes, with or without HCO60, by rat
      plasma proteins and the HCO60 micelle may form a complex with rat plasma
      proteins. Our findings suggest that liposomes containing large amounts of HCO60
      (more than 60 wt%) will be useful for delivering drug to the liver.

PMID- 8287046
TI  - Modification of liposomes by addition of HCO60. II. Encapsulation of doxorubicin
      into liposomes containing HCO60.
AB  - The efficiency of encapsulation of doxorubicin (DOX) into liposomes containing
      HCO60 was studied. Empty egg phosphatidylcholine (PC) liposomes containing
      various amounts of HCO60 were passed through a polycarbonate membrane filter (0.1
      micron). Closed vesicles were formed even with liposomes containing 90 wt% HCO60.
      DOX was encapsulated efficiently (more than 1 mg DOX/8 mg lipids) using a pH
      gradient method. HCO60 accelerated the leakage of DOX from liposomes into
      phosphate buffer at temperatures above 25 degrees C. HCO60 suppressed the leakage
      of DOX from egg PC/cholesterol (7/3, w/w) liposomes into phosphate buffer
      containing 50% fetal bovine serum (FBS). Studies on the interaction between
      liposomes and serum components using zeta potential and turbidity suggest that
      HCO60 prevents the liposomes from interacting with serum components.

PMID- 8287047
TI  - The protective effect of taurine on the biomembrane against damage produced by
      oxygen radicals.
AB  - The effect of taurine in protecting biomembrane against oxygen radicals was
      investigated using canine erythrocytes. 2,2'-Azobis(2-amidinopropane)
      dihydrochloride (AAPH), a water-soluble azo-compound, was used as the oxygen
      radical generator. Taurine suppressed erythrocyte hemolysis more effectively than
      alpha-alanine, used for comparison. To clarify the relationship to the lipid
      peroxidation, the amount of lipid peroxide was measured using liposomes prepared
      with egg yolk lecithin. However, the peroxidation was not suppressed by taurine.
      When intact erythrocytes were subjected to hemolysis by hyposmotic solutions,
      taurine suppressed the osmotic hemolysis more effectively than alpha-alanine.
      These results suggest that taurine does not have an antioxidative effect like
      vitamin E, but interacts with the biomembrane, and helps to protect it against
      damage caused by AAPH.

PMID- 8287048
TI  - Studies on thermophile products. VI. Activation of mouse peritoneal macrophages
      by bis(2-hydroxyethyl) trisulfide.
AB  - The biological effects of a cytotoxic substance (BS-1), isolated from Bacillus
      stearothermophilus UK563 and identified as bis(2-hydroxyethyl) trisulfide, on
      elicited mouse peritoneal macrophages induced by a casein injection, were
      investigated in vitro. BALB/c mouse macrophages treated or pretreated with BS-1
      (1-10 micrograms/ml) showed cytotoxicity against syngeneic DBA/2 mouse P815
      mastocytoma. BS-1 also showed weak cytotoxicity directly against P815 in the
      absence of macrophages. BS-1 significantly increased the glucose consumption of
      macrophages without producing cytotoxicity. This trisulfide compound increased
      nitric oxide formation, interleukin-1 production and prostaglandin E2 release in
      macrophages. It did not, however, increase the production of active oxygen
      species in macrophages, but it reduced cytochrome c in the presence of
      phagocytes. These results indicate that BS-1 activates macrophages to the
      cytolytic stage.

PMID- 8287049
TI  - New lectins from bulbs of Croccus sativum.
AB  - Four isolectins were isolated from bulbs of Croccus sativum (saffron), using
      affinity chromatography on mannan-Sepharose 4B, gel filtration and ion-exchange
      column chromatography in the presence of 8 M urea. The relative molecular masses
      of these lectins were determined by gel filtration to be approximately 48 kDa. On
      polyacrylamide gel electrophoresis, relative molecular masses of 8 kDa were
      obtained, suggesting that the lectins are hexamers. No carbohydrates were
      detected in the lectins. The lectins agglutinated the yeasts of Saccharomyces
      cerevisiae at a minimum concentration of 30 micrograms/ml, however, they did not
      agglutinate animal erythrocytes (human, sheep, rabbit and mouse) even at a
      concentration of 1000 micrograms/ml. In inhibitory experiments, mannan from
      Saccharomyces cerevisiae was the most potent inhibitor of C. sativum lectins.
      While D-mannose showed no inhibition, manno-oligosaccharides with either (alpha 1
      2, 1-3) or (alpha 1-6) linkages were potent inhibitors, suggesting that C.
      sativum lectins recognized manno-oligosaccharide units larger than mannobiose.
      Ovomucoid also exhibited potent inhibition, however, the other carbohydrates
      examined did not.

PMID- 8287050
TI  - Effect of anti-basic liver protein antibody-induced liver injury on hepatic drug
      metabolizing enzymes in C57 BL/6J mice.
AB  - We attempted to produce a model mouse with a liver injury resulting from an
      immunological mechanism in C57BL/6J mice, and the effect of hepatitis on the
      hepatic microsomal mixed-function oxidase system was studied. An experimental
      immunological liver injury model was caused by the intravenous injection of an
      anti-basic liver protein (BLP) antibody in mice which had been previously
      immunized with normal rabbit IgG (RGG) and complete Freund's adjuvant. C57BL/6J
      strain mice showed the highest susceptibility to the immunological liver injury.
      Typical histopathological changes in the liver included submassive hepatocellular
      necrosis and infiltration of lymphocytes into the portal tract and sinusoid area
      in a necrotic lesion. The liver injury in this model was markedly inhibited by
      the administration of prednisolone (20 mg/kg, p.o.), cyclophosphamide (15 mg/kg,
      i.p.), levamisole (10 mg/kg, p.o.), glycyrrhizin (50 mg/kg, i.p.) and
      cepharanthine (10 mg/kg, i.p.), which act on the immune system. Twenty-four hours
      after the injection of anti-BLP antibody, the activities of aminopyrine N
      demethylase, aniline hydroxylase and NADPH-cytochrome c reductase and the content
      of cytochrome P-450 were mostly reduced, whereas cytochrome b5 and NADH
      ferricyanide reductase were not. These results suggest that the experimental
      liver injury model in C57BL/6J mice is useful as a model of liver injury model,
      and its hepatitis was shown to inhibit the cytochrome P-450-dependent
      biotransformation of drugs in the mouse.

PMID- 8287051
TI  - Multiplicity of [3H]1,3-di-o-tolylguanidine binding sites with low affinity for
      haloperidol in rat brain.
AB  - Specific binding of [3H]1,3-di-o-tolylguanidine (DTG) was found not only in
      synaptic membrane fractions but also in subcellular fractions enriched of
      microsomes, nuclei and mitochondria/myelins, with different sensitivities to
      displacement by the antipsychotic haloperidol. The highest binding was detected
      in microsomal fractions followed by, in order of decreasing binding, fractions
      enriched in nuclei, synaptic membranes, mitochondria/myelins and homogenates.
      [3H]DTG binding was completely abolished by prior treatment of the synaptic
      membranes with a low concentration of Triton X-100. [3H]DTG binding reached a
      plateau within 30 min of the incubation at 2 degree C, whereas raising the
      incubation temperature to 30 degrees C resulted in marked shortening of the time
      required to attain equilibrium, without altering the binding at equilibrium. The
      binding was inhibited by haloperidol in a concentration-dependent manner over a
      concentration range of 1 nM to 0.1 mM but with a potency more than 100 times
      weaker than the value reported in the literature, irrespective of the termination
      method employed and the external proton concentrations. [3H]DTG binding was
      markedly displaced by a variety of compounds including sigma ligands,
      benzomorphan opiates and noncompetitive antagonists at the N-methyl-D-aspartate
      (NMDA) receptor in synaptic membranes of the cortex, hippocampus and cerebellum.
      However, sigma ligands such as haloperidol, DTG and (+)-3-(3-hydroxyphenyl)-N-(1
      propyl)piperidine were more potent in displacing [3H]DTG binding in cortical
      membranes than in hippocampal and cerebellar membranes, while the potencies of
      the NMDA antagonists were not significantly different from each other among these
      3 different central structures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287052
TI  - Synthetic Arg-Gly-Asp-Ser analogues of the cell recognition site of fibronectin
      that retain antimetastatic and anti-cell adhesive properties.
AB  - Synthetic peptide analogues of the Arg-Gly-Asp-Ser (RGDS) sequence of fibronectin
      in which the amino acid of Gly was substituted with another one, named X, i.e.
      Arg-X-Asp-Ser (R-X-DS), and N-terminal modified R-X-DS have been synthesized to
      examine their antimetastatic effects in murine lung or liver metastasis models,
      as well as the inhibitory effect on tumor cell invasion, migration and adhesion
      in vitro. R-X-DS [X = Leu (L) or D-Leu (1)], as well as RGDS at a high dose of
      3000 micrograms, significantly reduced the number of lung tumor colonies when
      they were co-injected with B16-BL6 melanoma. At a dose of 1000 micrograms/mouse,
      N-terminal modified R-X-DS, i.e. acetyl-D-R-X-DS [AcDR-X-DS: X = G, L or I],
      showed a more potent inhibitory effect on the lung or liver metastasis of B16-BL6
      melanoma or L5178Y-ML25 lymphoma cells, respectively, as compared with RGDS or R
      X-DS. AcDRLDS and AcDRIDS prevented the invasion of B16-BL6 cells into
      Matrigel/fibronectin- and Matrigel/laminin- coated filters, haptotactic
      migration, and the adhesion of the cells to both fibronectin- and laminin-coated
      substrates, whereas AcDRGDS inhibited only fibronectin-mediated cell functions.
      The intermittent i.v. administration of a water soluble vinylpolymer
      [poly(carboxyethylmethacrylamide), poly(CEMA)] containing R-X-DS (X = L or 1) or
      RGDS, following the subcutaneous inoculation of B16-BL6 cells, significantly
      inhibited spontaneous Jung metastasis as compared with multiple administrations
      of RGDS, R-X-DS or the untreated control.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287053
TI  - Estimation of absorbed dose to evacuees at pripyat-city using ESR measurements of
      sugar and exposure rate calculations.
AB  - The external absorbed doses in Pripyat-city resulting from the Chernobyl nuclear
      power plant accident have been evaluated from eight ordinary granulated sugar
      samples using the electron spin resonance method. The indoor and outdoor external
      doses to the people evacuated from Pripyat-city at about 36 h after the Chernobyl
      accident have been estimated using both data from the eight household sugar
      samples present in Pripyat-city prior to and during the accident and information
      on the type of buildings and survey-meter measurements of the exposure rates
      there. The absorbed dose to the evacuated people, as estimated from the exposure
      rates calculated in combination with the sugar dosimetry data, agree
      approximately with the reported average effective dose equivalent to such people,
      which was derived from both calculations and exposure-rate surveys. If each
      person in Pripyat-city could remember exactly the proportion of time spent
      indoors before being evacuated after the accident, the absorbed dose could
      roughly be estimated from the relationship between the documented external dose
      outdoors during the period between the accident and evacuation and the length of
      the period spent indoors by each individual prior to evacuation. It is suggested
      that as little as 1 g of sugar would be one of the most useful emergency
      dosimeters for people inside their dwellings, at least for absorbed doses greater
      than about 0.02 Gy.

PMID- 8287054
TI  - Computation of activities induced by 14 MeV neutrons for the elemental analysis
      of human tissues, skin and tooth enamel.
AB  - For planning experiments for neutron activation analysis investigations at 14
      MeV, suitable induced beta activities in Bq/g/neutron flux have been computed via
      appropriate reactions for the estimation of 19F, 23Na, 24Mg, 31P, 32S, 35,37Cl,
      39K, 40Ca, 55Mn, 56Fe, 66Zn, 63,65Cu, 107,109Ag and 208Pb. The computational work
      for (n,p); (n, alpha); (n,n') and (n,2n) reactions induced with 14 MeV neutrons
      are based on the pre-equilibrium emission mechanism and also the compound nucleus
      theory with otpical model potential and pairing energy corrections. The cross
      sections obtained by pre-equilibrium computer codes are reasonable and have been
      used in the present computations.

PMID- 8287055
TI  - Doses from radiocesium and 40K activities found in some tobacco leaves and
      cigarettes.
AB  - It has been found that tobacco leaves and cigarettes contain on the average 1.30
      +/- 0.40 Bq.g-1 of 40K which is a beta-gamma emitter. Besides due to the
      unfortunate Chernobyl accident tobacco leaves may contain 0.04 Bq.g-1 of 137Cs
      and 0.01 Bq.g-1 of 134Cs depending on their country of origin. From these
      activities, the annual dose equivalents and the 50 year committed dose
      equivalents from ingested and inhaled 134Cs, 137Cs and 40K through tobacco
      consumption are presented.

PMID- 8287056
TI  - A simple non-distillation method for the estimation of Ru-106 in urine.
AB  - A simple method has been developed for estimating Ru-106 in urine. Urine samples
      spiked with 3-50 Bq of Ru-106 and 200 micrograms of ruthenium carrier were
      initially oxidized using an HNO3-H2O2 mixture. Attempts to recover ruthenium by
      various preconcentration methods after the initial oxidation resulted in
      recoveries ranging from 10-54% depending on the experimental conditions. For near
      quantitative recoveries, the organic matter in urine was completely destroyed by
      wet ashing with HNO3-H2O2 (method A) or HNO3-H2O2 followed by H2SO4 treatment
      (method B). The ruthenium was oxidized to RuO4 using potassium periodate and
      allowed to react in situ with polyethylene powder. The polyethylene powder was
      separated, washed and its beta activity was counted. The recovery of ruthenium
      was 86.9 +/- 4.6% (RSD 5.3%) in method A; and 94.4 +/- 2.6% (RSD 2.8%) in method
      B. The minimum detection limit achieved was 0.59 Bq/dm3. Interferences due to Cs
      137 and Sr-90 were studied.

PMID- 8287057
TI  - Characterization of insoluble macromolecular Sn(II) complex and its application
      to the 99mTc labeling of human serum albumin-bearing mercapto groups.
AB  - A chelating ion exchange resin containing aminophosphonic acid groups was used as
      a polymer matrix for the preparation of an insoluble macromolecular Sn(II)(R-Sn)
      complex. Sn(II), which strongly bound to the surface of the polymer matrix by
      chelation, retained the ability to reduce 99mTc in the R-Sn complex. Human serum
      albumin-bearing-mercapto groups (HMA) was labeled with 99mTc at pH 2-3 using the
      R-Sn complex or SnCl2 as reducing agent. The 99mTc-HMA labeled with the R-Sn
      complex resulted in a higher sustained level of radioactivity in the blood of
      mice than the 99mTc-HMA labeled with SnCl2. These results suggest that the use of
      the R-Sn complex minimized Sn(II) contamination of the 99mTc labeling solution
      and can be used effectively as a reducing agent for 99mTc labeling of proteins
      containing sulfhydryl groups.

PMID- 8287058
TI  - Tissue distribution of liposomes prepared from synthetic amphiphiles after
      intraperitoneal injection into mice.
AB  - The tissue distribution of 99mTc-labeled vesicles prepared from synthetic
      amphiphiles containing an amino acid residue (synthetic liposomes) after
      intraperitoneal (i.p.) injection in Ehrlich solid tumor-bearing mice was
      investigated. Synthetic liposomes were labeled with 99mTc using stearylamine
      diethylenetriaminepentaacetic acid as a chelator. The accumulation of the
      synthetic liposomes in liver decreased and that in pancreas significantly
      increased in comparison with those after intravenous injection. Gamma camera
      images after i.p. injection also indicated high uptake of the synthetic liposomes
      in pancreas. The radioactivity of the synthetic liposomes in vitro was taken up
      most highly in pancreas among some excised organs.

PMID- 8287059
TI  - Formation of 1-[123I]iodobutane in labeling [123I]iomazenil by
      iododestannylation: implications for the reaction mechanism.
AB  - The benzodiazepine receptor tracer [123I]iomazenil (Ro 16-0154, IMZ) can be
      prepared in close to theoretical specific activity by the reaction of its
      tributyltin precursor (IMZ-SnBu3) with [123I]NaI in the presence of Iodogen.
      However, the labeling reaction is associated with variably high amounts of a
      volatile 123I byproduct. The purpose of these experiments was to characterize the
      volatile byproduct and to examine the effect on the course of the reaction of the
      following variables: solvent (MeOH, EtOH, HOAc, H2O), pH (2-7), oxidizing agent
      (chloramine-T, Iodogen, AcO2H), reaction temperature (22-128 degrees C) and
      structure of ArSnR3. The order of reactivity of oxidizing agents, at 22 degrees C
      for 30 min, was chloramine-T > Iodogen >> AcO2H. Raising the pH above 5.8 reduced
      the labeling, whereas raising the temperature increased the yield up to a maximum
      at 120 degrees (90%); at higher temperatures, decomposition occurred. The best
      conditions were 50 micrograms precursor, 50 microL 0.02 M chloramine-T; in
      aqueous HOAc (pH 3.3) at 120 degrees for 30 min. Variable amounts of volatile
      byproduct were observed for chloramine-T at different temperatures (2-21%) and
      for the three oxidizing agents at room temperature (3-22%). By contrast, the
      Bu3Sn derivatives of IBF, epidepride, beta-CIT and the Me3Sn derivative of beta
      CIT gave high labeling yields with peracetic acid at room temperature, and < or =
      2% volatile radioactivity. The volatile byproduct from the [123I]IMZ preparations
      was identified as I-[123I]iodobutane by its trapping characteristics and by its
      retention time in two different HPLC systems. Volatile activity was not generated
      in the absence of Bu3Sn precursor and was not due to the presence of impurities
      in the tributylstannyl precursor.

PMID- 8287060
TI  - Radioiodinated L-703,606: a potent, selective antagonist to the human NK1
      receptor.
AB  - A new, radioiodinated, NK1 selective radiotracer ([125I]L-703,606) was prepared.
      L-703,606 is an iodinated analog of the NK1 antagonist CP-96,345 in which the
      methoxy group has been replaced by an iodine substituent. [125I]L-703,606 was
      made from the corresponding trimethylsilyl compound by treatment with no carrier
      added Na 125I and an Iodobead in TFA. The tracer was prepared at a specific
      activity of approx. 1100 Ci/mmol and preliminary binding studies demonstrated
      that [125I]L-703,606 binds selectively to NK1 receptors with a kd = 0.3 nM. These
      results suggest that this radioligand will be useful for the biochemical and
      pharmacological characterization of the human NK1 receptor and, if labeled with I
      123, may be useful for non-invasive NK1 receptor imaging via SPECT.

PMID- 8287061
TI  - The AH-receptor: genetics, structure and function.
AB  - The AH-receptor is a ligand-activated transcription factor that regulates a
      number of biological responses to planar aromatic hydrocarbons. Interest in this
      receptor is related to its role in the toxic action of a variety of environmental
      chemicals, the simplicity and elegance of the murine genetics that led to its
      characterization and the distinctive mechanism by which this receptor activates
      gene expression. Recent cloning experiments have demonstrated that the AH
      receptor is structurally related to the Per, ARNT and Sim proteins. Members of
      this newly described gene family are characterized by two N-terminal domains, the
      most characteristic of which is a motif referred to as a PAS domain. In the AH
      receptor, this domain harbours sequences involved in the formation of a
      hydrophobic pocket that bind receptor agonists. Adjacent to the PAS domain in the
      AH-receptor, ARNT and Sim proteins is a basic/helix-loop-helix (bHLH) domain that
      appears to mediate heterodimerization and sequence specific DNA binding
      properties. The observation that the bHLH domain is present in the AH-receptor
      and the ARNT protein, a factor required for proper AH-receptor function, suggests
      that these proteins are heterodimeric partners that activate gene expression in a
      manner similar to Myc/Max and MyoD/E2A. The objectives of this review are to
      describe recent experimental results in this field and to use this information to
      develop a molecular model of AH-receptor mediated signal transduction.

PMID- 8287062
TI  - Expression of CYP1A1 and CYP1A2 genes in human liver.
AB  - Immunoblot analysis of human livers using a monospecific antibody to rat CYP1A2
      section demonstrated that the expression of CYP1A2 protein is highly variable in
      human liver. Quantitative PCR analysis was then employed to examine the
      interindividual variability of both CYP1A1 and CYP1A2 mRNAs in human liver.
      Hepatic content of CYP1A2 mRNA correlated significantly with levels of CYP1A2
      protein as analysed by immunoblot analysis (r = 0.58; p < 0.01). CYP1A2 mRNA
      content varied > 40-fold among individuals while CYP1A1 content varied > 20-fold.
      CYP1A2 mRNA was higher than CYP1A1 mRNA (approximately two to 30-fold) in livers
      of different individuals. The individual with the highest CYP1A1 and CYP1A2 mRNA
      amounts was a current smoker, but mRNA expression in two other smokers was within
      the range observed among nonsmokers. The expression of the two CYP1A mRNAs
      correlated highly (r = 0.72; p < 0.0005) when smokers were included, but the
      correlation was less significant (r = 0.62; p < 0.05) in nonsmokers. We amplified
      a full-length CYP1A2 cDNA clone by PCR from a liver which expressed extremely low
      amounts of CYP1A2 protein. Sequence analysis indicated that exon 4 was missing in
      this clone, but no other sequence changes were found. PCR analysis demonstrated
      that both the normally spliced mRNA and abnormally spliced mRNA could be detected
      in all human livers examined, but the normally spliced mRNA was more abundant
      than the splice variant. Therefore, sequence changes in the coding region of
      CYP1A2 did not account for the poor expression of CYP1A2 in this individual.

PMID- 8287063
TI  - Correlation between N-acetyltransferase activity and NAT2 genotype in Chinese
      males.
AB  - Eighty-four healthy Chinese male control subjects derived from an occupation
      based case-control study of bladder cancer were evaluated for hepatic N
      acetyltransferase activity by dapsone and for NAT2 genotype using allele-specific
      amplification of peripheral leukocyte DNA by the polymerase chain reaction. Fifty
      nine percent of the overall variation in acetylation activity was explained by
      genotype (p < 0.0001). The remaining variation in acetylation was not associated
      with dapsone N-hydroxylation activity, age, current smoking status, or weight in
      the study population, or within any genotype subgroup. Although acetylation
      activity in the homozygous mutant group did not overlap with the other genotype
      categories, there was moderate overlap in acetylation between the heterozygous
      mutant and wildtype groups, and substantial variation in acetylation within them.
      Considering all subjects with the identical NAT2 genotype as phenotypically
      similar and all subjects with differing NAT2 genotypes as phenotypically distinct
      may result in misclassification of metabolic risk factors in epidemiological
      investigations. As such, it would seem prudent, where possible, to collect both
      acetylation phenotype and NAT2 genotype data, since the advantages and
      limitations of these two sources of information complement, and serve to assess
      the accuracy of each other.

PMID- 8287064
TI  - Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese population
      associated with lower in vivo rates of sparteine metabolism.
AB  - A group of Japanese subjects were phenotyped for CYP2D6 activity by
      administration of sparteine and determination of urine metabolic ratios (MR). The
      CYP2D6 alleles from two subjects having a high MR, characteristic of slower rates
      of sparteine metabolism, were cloned in lambda EMBL3 and subjected to sequence
      analysis. One individual possessed a CYP2D6B allele, typically found in
      Caucasians, that is inactive due to an altered 3' splice recognition site and
      other potentially disruptive mutations. The second allele from this individual
      was identical to the wild type normal Caucasian CYP2D6 allele except for C188T
      and G4268C base differences in exons 1 and 9, respectively, that result in P34S
      and S486T amino acid substitutions. This allele was designated CYP2D6J. The
      second individual possessed two CYP2D6J alleles. PCR assays were performed to
      detect this allele and other alleles from a group of subjects exhibiting low
      rates of sparteine metabolism, i.e. with MRs > 1.5. Eleven CYP2D6J alleles were
      detected in 14 subjects exhibiting low rates of metabolism and including four
      individuals who were homozygous for this variant and had very low rates of
      sparteine metabolism (MRs > 2.5). In contrast, only two CYP2D6J alleles were
      found in 14 subjects having MRs of < 1.0. These data suggest that CYP2D6J encodes
      an enzyme having lower rates of sparteine metabolism.

PMID- 8287065
TI  - Acetylation phenotype and genotype in aboriginal leprosy patients from the north
      west region of Western Australia.
AB  - N-Acetyltransferases (NAT1, NAT2) play an important role in biotransformation of
      a number of drugs and carcinogens. A polymorphism in the metabolism of such
      compounds by NAT2 has been known for many years but it is only recently that the
      underlying molecular genetics has been elucidated. In the present study, we have
      correlated acetylation phenotype and genotype in a group of 49 Australian
      Aborigines (26 males and 23 females; mean age = 50.5 yr) from the Derby region of
      Western Australia. Phenotype was determined using caffeine and genotype by an
      allele-specific polymerase chain reaction. The percentages of slow and rapid
      phenotypes were 36.7 and 63.3%, respectively, while the distribution of alleles
      for the NAT2 gene was 41% for the wildtype and 2, 17 and 40% for the M1, M2 and
      M3 mutations, respectively. This is the highest proportion of M3 mutations
      reported for any ethnic population. The observed genotype proportions were not
      significantly different from those predicted by the Hardy-Weinberg Law (chi 2 =
      1.07, p > 0.05). Phenotype was predictable from genotype in 100% of patients. At
      the time of study, 29 of the Aborigines were receiving acedapsone intramuscularly
      for control of leprosy. Plasma dapsone concentrations in these patients were
      similar for both slow (n = 11) and rapid (n = 18) acetylators, suggesting that
      phenotype is unlikely to influence treatment outcome. The data show that
      Aborigines have a similar phenotype distribution to that of some Asian
      populations, but that there are differences in the frequencies of the M1, M2 and
      M3 mutant alleles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287066
TI  - Re-evaluation of the metabolism of carbocisteine in a British white population.
AB  - It has been claimed that the amino acid derivative carbocisteine is predominantly
      metabolized by sulfoxidation and that this pathway exhibits a genetic
      polymorphism. Moreover, those subjects with a 'poor metabolizer' phenotype have
      been thought to have a genetic predisposition to developing certain diseases. We
      have confirmed the observations of others that this marker drug does not undergo
      significant S-oxidation. Furthermore, a novel urinary metabolite, S
      (carboxymethylthio)-L-cysteine (CMTC) has recently been identified. To determine
      if a genetic polymorphism for this biotransformation pathway exists, metabolic
      ratios (% urinary excretion carbocisteine/% urinary excretion CMTC) for 120
      healthy volunteers were assessed using high-performance thin-layer
      chromatography. Urinary excretion of the parent drug ranged from 6% of the dose
      administered to 56% (mean +/- SD, 23.4 +/- 0.8%). No cysteinyl sulfoxide
      metabolites were identified in the urine samples. The amount excreted as CMTC
      exhibited a 12-fold variation but only accounted for mean of 4.4% (1-12%) of the
      dose given. Two individuals initially had high metabolic ratios (> 30), however,
      on rechallenge both their MRs were less than 5. Therefore, carbocisteine is not
      an appropriate probe drug for sulfoxidation. The formation of the novel
      metabolite CMTC appears to exhibit polymorphism, although the considerable intra
      subject variation for its formation does not allow assignment of a phenotype.

PMID- 8287067
TI  - Interaction of a conserved peptide domain in recombinant human ventricular myosin
      light chain-2 with myosin heavy chain.
AB  - Recent work on molecular genetics of mammalian contractile proteins has provided
      valuable insights into the basis of the heterogeneity of muscle proteins and
      their regulated expression during development, yet information on the precise
      role(s) of light chains in actomyosin interaction and muscle function is still
      lacking. The selective increase in ventricular myosin light chain-2 (MLC2) in
      hypertrophied heart muscle has been implicated as a compensatory feature of
      myosin, but its relevance to myosin function is not known. To investigate the
      role of cardiac MLC2, we have isolated a full-length cDNA clone for human
      ventricular MLC2 and produced a full-length and N-terminal deleted MLC2
      polypeptides in Escherichia coli using the bacterial expression vector pT7-7
      system. The interaction of recombinant MLC2 with myosin heavy chain (MHC) and its
      subfragment-1 was studied using the full-length and truncated recombinant
      polypeptides. The results demonstrated that the bacterially produced full-length
      human cardiac MLC2 exchanges effectively with the native MLC2 and binds with
      specificity to MHC and to intact myofibrils. Domain mapping by deletion and in
      vitro exchange/competition analysis with a synthetic peptide suggests that a
      conserved central domain in MLC2 participates in the functional association of
      the two myosin subunits.

PMID- 8287068
TI  - Conformation changes of p53 proteins in regulation of murine T lymphocyte
      proliferation.
AB  - This report shows that p53 gene expression is required for proliferation of
      Concanavalin A (ConA)-stimulated murine T lymphocytes. p53 gene-specific
      antisense oligodeoxynucleotides strongly inhibited expression of p53 gene in T
      lymphocytes, causing suppression of ConA-induced cell proliferation. In contrast,
      the complementary-sense oligomers had no inhibitory effects. Northern and
      immunoprecipitation-blotting assay data, however, showed no change in p53 mRNA
      and proteins synthesized in T lymphocytes before and after ConA stimulation. p53
      proteins in the resting and ConA-stimulated T cells had different
      immunoreactivity with specific monoclonal antibodies. p53 from resting T cells
      only reacted with "wild-type form" p53-specific monoclonal antibody (PAb246);
      whereas, p53 from ConA-stimulated T cells was recognized by "mutant-form" p53
      specific monoclonal antibody (PAb421). These results suggest that the
      conformation of p53 proteins in resting and ConA-stimulated T cells are
      different. The p53 conformation changes may be related to the regulation of
      murine T lymphocyte proliferation.

PMID- 8287069
TI  - Identification of specific intracellular domains of the human ETA receptor
      required for ligand binding and signal transduction.
AB  - We have investigated the function of the C-terminal and the third intracellular
      domains of the ETA receptor by expressing truncated and mutated ETA receptors in
      COS-7 and CHO cells. All the C-terminal truncated ETA receptors were produced at
      a similar expression level and were detected in the cell membrane using indirect
      immunostaining. The sizes of the truncated ETA receptors were decreased in
      proportion to the molecular mass of the truncated amino acid sequence. When the
      ligand binding activities were determined for various truncated ETA receptors, it
      was found that more than eight amino acid residues at the proximal cytoplasmic
      tail of the ETA receptor were required for ET-1 binding. In addition, the
      deletion of 16 C-terminal amino acid residues from the third intracellular loop
      severely decreased the ligand binding activity. It seems that deletion of these
      cytoplasmic domains of the ETA receptor influences the three-dimensional
      structure of the ligand binding site located in the extracellular domains. The
      ETA receptor required more than 13 amino acid residues in the proximity of C
      terminal cytoplasmic tail and 10 amino acid residues in the C-terminal region of
      the third intracellular loop to induce the ET-1 dependent increase in
      intracellular calcium concentration. Both regions are possibly coupled with G
      protein to transmit the ET-1 signal.

PMID- 8287070
TI  - Expression and subcellular locations of two forms of nucleolar protein B23 in rat
      tissues and cells.
AB  - Protein B23 (Mr/pI = 38,000/5.1) is a major RNA-associated nucleolar
      phosphoprotein and putative ribosome assembly factor. Previous cDNA and genomic
      analyses indicated the presence of two forms of the protein (B23.1 and B23.2)
      which arise from a single gene via alternative splicing. Expression of the two
      B23 isoforms in rat tissues cells has been studied at the mRNA level using
      northern blot and RNA-polymerase chain reaction analyses and at the protein level
      by western blotting. In all tissues examined, the relative amount of B23.1 mRNA
      was much higher (3-6-fold) than B23.2 mRNA. For B23.1, the level of mRNA and
      protein expression was highest in Novikoff hepatoma cells, followed by testis,
      liver, and kidney. This suggests that B23.1 expression is correlated with the
      rate of proliferation of the tissue and/or the rate of ribosome biogenesis. In
      contrast, the amount of B23.2 mRNA did not vary significantly among the three
      normal tissues, although it was elevated in Novikoff hepatoma cells. Similarly,
      the B23.2 protein was barely detectable in the normal rat tissues, but
      significant quantities were found in the Novikoff cells. In cell fractionation
      experiments, B23.1 was predominantly found in nucleoli, whereas B23.2 was located
      in cytoplasmic fractions and appeared to be associated with cytoskeletal
      elements. These studies suggest that the two protein B23 isoforms are engaged in
      very different functions.

PMID- 8287072
TI  - Platelet membrane-actin interaction.
AB  - In order to investigate how human platelet membranes associate with cytoskeletal
      proteins, purified membranes were extracted with 0.6 M KI (potassium iodide)
      followed by extraction with 1% octyl glucoside. The depleted membranes contain a
      significant amount of actin (5% of the actin that was originally present in the
      purified membranes) which is resistant to extraction by 0.6 M KI. We have
      examined how this actin interacts with the membrane skeletal fraction and find
      that the actin is not associated with the membrane directly or indirectly through
      any of the major transmembrane glycoproteins (GpIb, GpIIb, and GpIIIa), or any
      known specific linker proteins such as actin binding protein (ABP), alpha
      actinin, or spectrin. The results of an analysis of the membrane skeletal
      preparation using nonreducing sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) does indicate, however, that the actin, along with
      other proteins, exists in the form of two high molecular weight complexes. We
      have examined the effect of potassium iodide-octyl glucoside (KI-OG) extracted
      membranes upon (1) the polymerization of rabbit muscle G-actin, and (2) the actin
      activated Mg(2+)-dependent ATPase activity of rat skeletal muscle myosin. Based
      on the results of these experiments we have concluded that the actin is available
      for interaction with exogenously added proteins and that it might possibly be in
      a filamentous form. These results are compelling considering the role that the
      cytoskeleton is thought to play in the physiological functioning of the platelet.

PMID- 8287071
TI  - Androgenic regulation of the expression and phosphorylation of prostatic
      nucleolar protein B23.
AB  - Protein B23 is a nucleolar and nuclear matrix phosphoprotein which has been
      implicated in ribosomal assembly and/or rRNA processing. Since androgen action in
      the prostate is accompanied by early changes in rRNA synthesis, we have
      investigated androgenic regulation of protein B23 expression and phosphorylation
      in rat ventral prostatic nuclei. The mRNA for prostatic protein B23 was
      relatively stable and decreased only after several days of androgen deprivation.
      However, androgen deprivation resulted in a rapid change in the amount and
      phosphorylation of protein B23 in prostatic nuclei, which was reversed on
      administration of androgens to orchiectomized animals. Phosphorylation of protein
      B23 appears to be catalyzed primarily by casein kinase 2 (CK-2). Early androgenic
      changes in phosphorylation of protein B23 appear to relate more to modulations in
      the protein kinase activity than in the amount of protein B23. The androgen
      mediated enhancement in the amount of protein B23 and its phosphorylation
      precedes the cellular proliferative phase following androgen administration to
      castrated rats, and appear to be temporally concordant with the rRNA synthesis in
      the tissue. The androgen mediated changes in the amount and phosphorylation of
      protein B23 are specific to the prostate and are not detected in the liver
      nuclei. Thus, androgenic regulation of the amount and phosphorylation of
      prostatic protein B23 may be related to the early changes associated with
      androgen mediated growth of the gland.

PMID- 8287074
TI  - Bibliography of cellular and molecular biology research.

PMID- 8287073
TI  - Unique ultrastructural characteristics of pigeon anterior latissimus dorsi
      muscle.
AB  - The pale anterior latissimus dorsi (ALD) muscle of the adult pigeon was studied
      ultrastructurally. There were embryonic heart and skeletal muscle features
      present. These included loosely packed myofibrillar apparatus, subsarcolemmal
      pads of sarcoplasm, abundant pinocytotic vesicles, and tubular aggregates. The
      latter were focal, smooth surfaced, and bilaminar. An increased accumulation of Z
      disk material was widespread in the muscle fibers. There were distinct
      sarcolemmal evaginations which possess knob-like projections. Myocellular
      extensions were evident at muscle fiber ends and these produced bud-like
      configurations in transverse section. These features in the normal adult ALD
      rules out the assumption that they represent a denervation phenomenon, as
      suggested by others.

PMID- 8287075
TI  - Common etiologies and new approaches to management of poisoning in pediatric
      practice.
AB  - Accidental exposure to drugs and household products in young children and self
      poisoning by adolescents are common clinical problems of important concern to the
      general pediatrician. This article reviews new developments in the field of
      pediatric toxicology including 1) epidemiologic data collected from poison
      centers and hospital admissions that illustrate the changing spectrum of
      pediatric poisonings; 2) progress in identifying clinical features or laboratory
      tests predictive of outcome in specific poisoning; 3) advances in and limitations
      involving decontamination methods and antidote therapy in different toxic
      ingestions; and 4) recent investigations toward prevention of pediatric poisoning
      with an emphasis on barriers to compliance.

PMID- 8287076
TI  - New developments in pediatric lead poisoning.
AB  - In October 1991, the Centers for Disease Control and Prevention issued new lead
      guidelines, dramatically lowering the intervention level from 25 micrograms/dL of
      lead in blood to only 10 micrograms/dL and calling for universal screening. This
      review summarizes recent research findings on the effects of lead exposure on
      cognitive abilities and presents current information on sources of exposure to
      lead, methods of screening for lead poisoning, and options for treatment.

PMID- 8287077
TI  - The psychobiology of childhood stress.
AB  - Recent psychobiologic research has provided new insights into the interplay
      between constitutional and environmental etiologies in stress-induced childhood
      illness. Individual differences in both psychobiologic reactivity and physiologic
      self-regulation may substantially influence a child's internal stress responses.
      In addition, the physiologic consequences of a given environmental stressor may
      depend critically on the developmental stage in which the stressor occurs.
      Behavioral changes associated with early exposures to stressors may be linked to
      alterations in central nervous system monoamine production and metabolism.
      Evidence for developmental and psychobiologic changes in response to very early,
      even prenatal, stressors suggests that environmental and genetic contributions to
      stress response profiles may ultimately be difficult to disentangle.

PMID- 8287078
TI  - Infant mortality.
AB  - Infant mortality continues to be a major public health issue in the United
      States. Although some preventive strategies for neonatal mortality are emerging
      for congenital malformations, notably neural tube defects, the prevention of
      preterm deliveries among disadvantaged populations remains elusive, suggesting
      the need for different approaches to women's health needs. Despite the lack of
      success in preventing preterm birth, neonatal mortality rates continued to
      decline substantially, a decline attributed to improvements in neonatal intensive
      care associated with surfactant use. The increasing survival of very preterm
      infants continues to raise questions about their longer term outcomes especially
      with several recent studies on difficulties in school, and about the need for
      postdischarge developmental interventions. Attempts to decrease postneonatal
      mortality received marked attention with the recommendations for specific
      positioning to prevent sudden infant death syndrome and heightened attention to
      increased immunization completion rates. The dismal ranking of the United States
      in infant mortality rates among industrialized countries, however, continues to
      present a social policy challenge.

PMID- 8287079
TI  - Fat-soluble vitamin deficiency in infants and children.
AB  - Fat-soluble vitamin deficiency is known to result in various complications that
      may be prevented if the problem is recognized and managed appropriately. In
      infants and children with chronic cholestasis, replacement therapy of the fat
      soluble vitamins, vitamins A, D, E, and K, may prove extremely difficult because
      low concentrations of intraluminal bile acids lead to malabsorption of these
      compounds and other fat-soluble substances. Recent progress in the use of a water
      soluble form of vitamin E, d-alpha-tocopheryl polyethylene glycol-1000 succinate,
      has enabled correction of vitamin E-deficiency states in these patients. It has
      also allowed for the admixture and coadministration of other fat-soluble vitamins
      and compounds in d-alpha-tocopheryl polyethylene glycol-1000 succinate to enhance
      their absorption. For managing vitamin K deficiency, similar success has been
      achieved using a vitamin K compound solubilized in glycocholate and lecithin.
      Vitamin A deficiency has been implicated in the higher incidence of childhood
      mortality and morbidity in Third World countries. Increased risk of childhood
      cancer has recently been associated with intramuscular injection of vitamin K to
      newborns. Finally, it is worth noting that among the pediatric population,
      exclusively breastfed infants, in general, are at risk for hypovitaminosis D, and
      at even greater risk in the absence of adequate exposure to sunlight or when the
      maternal diet is not sufficient to provide for vitamin D requirements.

PMID- 8287080
TI  - Pathogenesis of food allergy in infants.
AB  - Three main factors are needed for an infant to develop allergy: allergen
      exposure, a genetic predisposition, and contributory factors. Recent literature
      suggests that the incidence of in utero sensitization might have been
      underestimated up to now. A number of papers provide evidence that atopic
      dermatitis should be regarded as a manifestation of food allergy. The case for an
      immunologic mechanism of food allergy has been indirectly strengthened because of
      the apparent association between increased levels of antibodies to cow's milk
      proteins and insulin-dependent diabetes mellitus. The vast majority of recent
      papers deal with the prevention, and thus indirectly with the pathogenesis, of
      cow's milk protein allergy. In general, studies focusing on the prevention of
      cow's milk protein allergy in at-risk infants report "satisfactory" results,
      suggesting that in a majority of infants the decreased or reduced exposure to
      native cow's milk proteins not only delays but also eliminates cow's milk
      allergy. Experience with hypoallergenic formulas in therapeutic situations is
      disappointing. Skin-prick tests with hypoallergenic formulas are recommended
      before such a formula can be considered in allergic infants.

PMID- 8287081
TI  - Gastrointestinal infection in children.
AB  - Infections of the gastrointestinal tract remain an important cause of childhood
      morbidity and mortality worldwide. A number of pertinent articles have appeared
      in the past year, advancing our understanding of 1) Helicobacter pylori-induced
      gastroduodenal disease, 2) Escherichia coli O157:H7-mediated diarrhea, and 3)
      newer gastrointestinal parasites that cause diarrhea. These are the topics of
      review.

PMID- 8287082
TI  - Esophageal disorders in infants and children.
AB  - Although the esophagus functions simply as a conduit between the mouth and the
      more distal gastrointestinal tract, its physiology and pathophysiology display a
      complexity that contrasts with that simple function. Thus there are still
      mysteries about this "tube" and its disorders, and each year brings new
      revelations. Most attention continues to focus on gastroesophageal reflux, its
      emerging pathophysiology, multiple manifestations, various diagnostic techniques,
      and improving methods of treatment. Complications of gastroesophageal reflux,
      including optimal ways of preventing and treating them, have been explored
      further. Other aspects of esophageal motility and dysmotility and other causes of
      inflammation and injury of the esophagus have also been studied during the past
      year. The surgical literature, especially, continues to struggle with congenital
      esophageal lesions, particularly esophageal atresia and stenoses.

PMID- 8287083
TI  - A 2-year-old girl with hematemesis, melena, and splenomegaly.

PMID- 8287084
TI  - Transthoracic versus transesophageal echocardiography in the pediatric patient.
AB  - The development of pediatric transesophageal ultrasound imaging represents an
      important advance in the diagnosis and treatment of the child with congenital
      heart disease. Although primary diagnostic transesophageal studies are seldom
      indicated in infants and unoperated children, they have an important role in the
      older child especially where there has been prior cardiac surgery. Diagnostic
      studies are most appropriate for abnormalities of venous return, the atria,
      atrioventricular valves, and the left ventricular outflow tract. Two other
      important areas in which transesophageal imaging is playing an increasing role in
      the treatment of the pediatric patient is in monitoring interventional
      catheterization and in the intraoperative and immediate postoperative monitoring
      of surgical repair.

PMID- 8287085
TI  - Drugs and ablation in the treatment of supraventricular tachyarrhythmias in
      children.
AB  - The vast majority of children who have symptoms (ie, cardiac failure,
      palpitations, dizziness) due to supraventricular tachycardias are successfully
      managed by medical treatment. Antiarrhythmic drug therapy may be complicated by
      side effects or become ineffective so that radiofrequency catheter ablation,
      which destroys the myocardial structure responsible for arrhythmias, can now
      offer an attractive option to lifelong drug therapy. Immediate results for
      supraventricular tachycardias due to a reentry mechanism or to an atrial ectopic
      focus are good, with a success rate over 80% and rare immediate complications.
      However, the long-term sequelae of the procedure on the growing heart have not
      been established and the risk of subsequent atrial and ventricular arrhythmias
      must be considered in young patients. For this reason, I believe that today,
      radiofrequency ablation should be reserved for young patients who have life
      threatening symptoms or who have arrhythmias that are refractory to medical
      treatment, and for older patients who will need a lifelong drug therapy.

PMID- 8287086
TI  - Comparison of risks and short- and long-term results of balloon dilatation versus
      surgical treatment for pulmonary and aortic valve stenosis and restenosis and
      coarctation and recoarctation of the aorta.
AB  - Balloon valvuloplasty and angioplasty have become accepted alternatives to
      surgery for valvar stenosis and coarctation of the aorta. Balloon dilation avoids
      a potentially painful operation, the long postoperative recovery, and at the same
      time offers substantial cost savings. However, such advantages are meaningless if
      the safety of the interventional procedure does not match or surpass the results
      of conventional surgery. This review summarizes a number of studies that compare
      the natural history of surgical therapy with that of balloon pulmonary and aortic
      valvuloplasty and balloon coarctation angioplasty. It appears that, regardless of
      age, balloon valvuloplasty is preferable to surgical valvotomy. For both aortic
      stenosis and coarctation of the aorta, balloon valvuloplasty and surgical
      valvotomy produce comparable relief of the hemodynamic obstruction. However,
      because the length of follow-up after the balloon angioplasties has been short,
      the actual risk of developing severe aortic regurgitation (postaortic
      valvuloplasty) and aortic aneurysms (postcoarctation angioplasty) has not been
      trivial, a large prospective follow-up of both of these interventional procedures
      will be mandatory before either can be judged superior to surgical therapy.

PMID- 8287087
TI  - Determinants of short- and long-term outcome in the surgical correction of
      tetralogy of Fallot.
AB  - Although biventricular correction of tetralogy of Fallot has been with us for
      well over three decades, the optimal treatment of these patients continues to be
      debated, and surgical techniques refined. There can be no doubt that operative
      mortality has improved, and no matter which approach is chosen, an early
      mortality of less than 5% should be easily achievable. As with most other areas
      of pediatric cardiology and cardiac surgery, these admirable early results are
      truly only the beginning. While reflecting the results of surgery in an earlier
      era, some of the long-term follow-up data beginning to emerge from studies of
      these patients, particularly in regard to the effect of pulmonary incompetence,
      is compelling and must be taken into account when deciding the optimal surgical
      treatment for the individual child presenting today with tetralogy of Fallot.
      This article reviews some of the more recent data regarding the functional
      outcome of these patients as well as the surgical approaches that have been
      developed to address them.

PMID- 8287088
TI  - Atopic disease, rhinitis and conjunctivitis, upper respiratory tract infections,
      and insect stings and snake bites.
AB  - In this section we review four broad topics in pediatrics: atopic disease,
      rhinitis and conjunctivitis, upper respiratory tract infections, and insect
      stings and snake bites. The first three topics comprise three of the most
      commonly encountered problems in pediatric practice. Although the fourth topic
      accounts for a relatively small number of office visits, it generates a great
      deal of concern among our patients and their parents. There have been significant
      contributions to the pediatric literature in each of these areas over the past
      year and we review those of particular interest.

PMID- 8287089
TI  - Slice cultures as a model to study entorhinal-hippocampal interaction.

PMID- 8287090
TI  - Constituents involved in glutamate receptor signaling.

PMID- 8287091
TI  - Alterations of signal transduction in the lesioned entorhinal-hippocampal system:
      a mini-review on Alzheimer's disease-related changes and experimental data.

PMID- 8287092
TI  - Cellular and subcellular distribution of receptors in the entorhinal-hippocampal
      system: morphologic and biochemical aspects.

PMID- 8287093
TI  - Receptor distribution in the human and animal hippocampus: focus on muscarinic
      acetylcholine receptors.

PMID- 8287094
TI  - Tissue sections as culture substrates: overview and critique.

PMID- 8287095
TI  - Laminar and region-specific cell surface markers in the entorhinal cortex and
      hippocampus.

PMID- 8287096
TI  - Comparative anatomy of the entorhinal cortex and hippocampus in mammals.

PMID- 8287097
TI  - Maturation of medial temporal lobe memory functions in rodents, monkeys, and
      humans.

PMID- 8287098
TI  - Role of the hippocampal formation in learning and memory.

PMID- 8287099
TI  - Cell assemblies, coherence, and corticohippocampal interplay.

PMID- 8287100
TI  - Expression and processing of pathologic proteins in Alzheimer's disease.

PMID- 8287101
TI  - Entorhinal-hippocampal interaction in mnestic disorders.

PMID- 8287102
TI  - Transneuronal changes in the lesioned entorhinal-hippocampal system.

PMID- 8287103
TI  - In vitro and in vivo models to unravel the potential roles of beta/A4 in the
      pathogenesis of Alzheimer's disease.

PMID- 8287104
TI  - Ontogeny of the entorhinal cortex.

PMID- 8287105
TI  - Cellular and molecular pathology in Alzheimer's disease.

PMID- 8287106
TI  - Plasticity in the entorhinal-hippocampal system.

PMID- 8287107
TI  - Structural correlates and cellular mechanisms in entorhinal-hippocampal
      dysfunction.

PMID- 8287108
TI  - Neuronal cell types in entorhinal cortex and hippocampal formation of man and
      other mammalia: an interspecies comparison.

PMID- 8287109
TI  - Morphological and functional correlates of borders in the entorhinal cortex and
      hippocampus.

PMID- 8287110
TI  - Organization of the entorhinal-hippocampal system: a review of current anatomical
      data.

PMID- 8287111
TI  - Metabolic alterations common to neural and non-neural cells in Alzheimer's
      disease.

PMID- 8287112
TI  - Perineuronal nets of extracellular matrix around parvalbumin-containing neurons
      of the hippocampus.

PMID- 8287113
TI  - The neuronal cytoskeleton and its role in axonal and dendritic plasticity.

PMID- 8287114
TI  - Entorhinal cortex-hippocampal interactions in normal and epileptic temporal lobe.

PMID- 8287115
TI  - Activity-dependent changes in structure and function of hippocampal neurons.

PMID- 8287116
TI  - Structural analysis of a new highly metastatic cell line PaTu 8902 from a primary
      human pancreatic adenocarcinoma.
AB  - The new cell line PaTu 8902 was established from a human pancreatic grade II
      adenocarcinoma of ductal origin. In early passages, cultured cells showed a high
      degree of heterogeneity in terms of their morphology and the number of
      chromosomes per cell. When transplanted subcutaneously into nude mice, these
      cells grew as tumors with a similar morphology and differentiation (grade II) to
      the primary tumor. In contrast, after prolonged cultivation, cells were more
      homogenous in terms of their morphology and number of chromosomes per cell, and
      the corresponding nude mouse xenografts were less differentiated (grade III).
      When cells from late passages were injected intravenously into nude mice, lung
      metastases occurred after 3-4 weeks. In addition, tumor cells were found in the
      wall of the esophagus and in the pleural cavity, indicating a high metastatic
      potential for PaTu 8902 cells in nude mice.

PMID- 8287117
TI  - Characterization of the inflammatory cell populations in normal colon and colonic
      carcinomas.
AB  - Little is known about the nature of the mucosa-associated immune system within
      the normal colon, or about the immune response to colon carcinoma. In this study
      inflammatory cells (ICs) in 14 normal colons and 14 carcinomas were
      characterized. Overall inflammation, lymphocytes, plasma cells, neutrophils, and
      eosinophils were graded in routine H & E sections. Frozen sections were stained
      by an immunoperoxidase technique using antibodies to the T cell associated
      antigens CD2, CD7, CD4, CD8, and T cell receptors alpha beta and gamma delta. B
      cells were identified with CD20, macrophages with CD68, and Class II antigen with
      anti-HLA DR. Each cell type was semiquantitatively graded in 10 high power fields
      (HPFs) in the lumenal half (LH) or basal half (BH) of the normal mucosae, and in
      epithelium or stroma of the carcinomas. In normal colons, ICs were more frequent
      in LH than in BH. Plasma cells, lymphocytes and monocytes predominated. Subtyping
      of lymphocytes showed that CD4+ TCR alpha beta + T lymphocytes were most numerous
      in the lamina propria. Lymphocytes within the epithelium were CD8+ T cells.
      Around carcinomas the overall grade of ICs was 1+ in the majority of cases.
      Plasma cells, CD4+ and CD8+ cells with the TCR alpha beta receptor, and
      macrophages were most frequent. Lymphoid aggregates of both T and B cells were
      frequent. CONCLUSIONS: 1. Normal colon contains a diffuse luminally oriented
      population of TCR alpha beta+ CD4+ T cells, plasma cells, macrophages and class
      II antigen-expressing cells in the lamina propria.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8287118
TI  - Differential expression of alpha 1-antichymotrypsin in the aged human brain.
AB  - The localization of alpha 1-antichymotrypsin (ACT) mRNA and ACT immunoreactivity
      (ACT-IR) were examined in 12 brains obtained at post-mortem from elderly
      patients, four of whom had Alzheimer's disease. A biotinylated oligonucleotide
      probe was used for in situ hybridization histochemistry and the relationship
      between the expression of both ACT mRNA and ACT-IR and the extent of beta protein
      or tau deposition were investigated. The extent of beta-plaques, tau-tangles, and
      ACT-IR were rated from (-) to (++). In brains without plaques and tangles, there
      were no detectable ACT mRNA signals in the gray matter, and those in the white
      matter were weak; in these brains, ACT-IR was generally weak. The brains with
      beta-plaques but no tangles showed weak ACT mRNA expression in astrocytes of both
      the gray and white matter; they also showed weak ACT-IR in the astrocytes. In the
      brains from patients with Alzheimer's disease with both plaques and tangles, ACT
      mRNA was expressed intensely in a majority of the astrocytes in the white and
      gray matter. Some senile plaques-associated astrocytes expressed ACT mRNA and ACT
      IR was strong in the white matter astrocytes. ACT-IR and ACT mRNA expression in
      astrocytes was correlated with the extent of beta and tau depositions.

PMID- 8287119
TI  - Morphogenesis of the protein secretory system in PC12 cells infected with
      Japanese encephalitis virus.
AB  - Infection of PC12 cells with Japanese encephalitis (JE) virus caused marked
      proliferation of the protein secretory system. Accordingly, in this study the
      morphogenesis of the secretory organelles, i.e., rough endoplasmic reticulum
      (RER) and the Golgi apparatus, in JE virus-infected PC12 cells was analyzed by
      electron microscopical observation. Starting 24 h postinoculation (p.i.), a
      structure that represented nascent RER appeared in the cytoplasm in the form of
      rows of ribosomes which surrounded membrane-unbounded, electron-lucent lacunae in
      a reticular, honey-comb pattern (reticular RER). Although the reticular RER
      lacked membrane components, its lacunae contained progeny virions, indicating
      that the rows of ribosomes synthesized the viral proteins and discharged them
      into the lacunae for the viral assembly. The reticular RER apparently transformed
      into the familiar lamellar RER during the RER morphogenesis as the lacunae
      coalesced to form flat cisternae and RER membrane assembled to border the
      cisternae. These findings indicated that the proliferating RER was the site of
      not only active protein synthesis but also active membrane biogenesis. The
      proliferating RER released a large number of membrane vesicles including virion
      carrying vesicles into the cytoplasm. These vesicles congregated in the
      juxtanuclear region, especially around the centrioles, and fused to existing
      Golgi complexes for enlargement or fused among themselves to form new Golgi
      complexes. The present study, therefore, indicated that (a) nascent RER was
      formed by polysomes that arranged themselves in rows of ribosomes without
      participation of a preexisting membrane framework of endoplasmic reticulum (ER),
      (b) membrane components of RER were assembled de novo within the structure during
      the RER morphogenesis, and (c) RER released membrane vesicles that moved to the
      Golgi apparatus and contributed to the morphogenesis of the Golgi apparatus.
      Possible causative mechanisms involved in the proliferation of the secretory
      system in JE virus-infected PC12 cells are discussed.

PMID- 8287120
TI  - Phospholipid loss in dying platelets.
AB  - The death of a cell results in a large amount of membrane lipid, predominantly
      phospholipids and cholesterol, that must be eliminated. In this study, we have
      examined what happens to phospholipids in dying rat platelets. Rat platelets were
      incubated for up to three days following their activation with thrombin. Platelet
      death occurred during the first day of incubation. This was indicated by a
      complete loss of platelet lactate dehydrogenase into the incubation medium. The
      platelets progressively lost over one-half of their phospholipid content during
      the three days of incubation. Cholesterol and sphingomyelin (the phospholipid
      with the highest affinity for cholesterol) were not lost during the same period.
      Our findings suggest that significant degradation of cellular non-sphingomyelin
      phospholipid can be triggered by cell death. The preservation of sphingomyelin in
      dying platelets, may be an adaptive response to maintain cholesterol in a
      solubilized state within dying cells.

PMID- 8287121
TI  - Granuloma formation in the liver of Balb/c mice intoxicated with carbon
      tetrachloride.
AB  - Hepatic granulomas induced by a single or several subcutaneous injections of
      carbon tetrachloride (CCl4) in Balb/c mice were examined electronmicroscopically
      and immunocytochemically. Stellate cells (fat-storing cells; lipocytes; Ito
      cells) were identified by the detection of cytoplasmic desmin, while T
      lymphocytes and monocytes/macrophages were identified with monoclonal antibodies
      Thy 1.2 and MOMA-2, respectively. Following pericentral necrosis induced with
      CCl4, clear foci containing lymphocytes, monocytes, macrophages and
      perisinusoidal stellate cells occurred in the surrounding hepatic parenchyma on
      day 5. These clear foci developed to granulomas with increasing numbers of
      macrophages and stellate cells. Mitotic and apoptotic figures in randomly
      distributed macrophages, and direct contacts between macrophages and stellate
      cells were frequently seen within the granulomas. The stellate cells were
      characterized by a well-developed granular endoplasmic reticulum and Golgi
      complex. Collagen fibrils were closely applied to the stellate cells and
      connective tissue septa extended between neighboring granulomas and/or the
      pericentral necrotic areas after several injections of CCl4. CCl4-induced hepatic
      granulomas provide a model for investigating paracrine and/or autocrine
      modulation within a well-organized microenvironment during progressive hepatic
      inflammation and fibrosis.

PMID- 8287122
TI  - Protective effect of silymarin on rat liver injury induced by ischemia.
AB  - The effect of silymarin on liver cell damage induced by ischemia was studied in
      rats fasted for 24 h. In the first series of experiments in vitro ischemia was
      induced by storing tissue blocks in closed vials at 37 degrees C for 15, 30, 45
      and 60 min. Cell injury was detected by the cytophotometrical measurement of
      glycogen phosphorylase activity in unfixed cryostat sections demonstrated by a
      modified histochemical procedure. In the second series of experiments in vivo
      ischemia was provoked by clamping the afferent vessels to the median and left
      lateral lobes of the liver for 60 min, followed by removal of the clamp and
      reperfusion. The extent of cell damage was determined by measuring the ALAT and
      ASAT activities in serum at 1, 3, 6 and 24 h after ischemia and by quantifying
      the extent of necrosis in the liver after 24 h reperfusion by measuring the
      unstained areas in cryostat sections incubated for lactate dehydrogenase
      activity. Silymarin (100 mg/kg b.w.) was administered intravenously at 5 min
      before both the induction of ischemia and the restoration of blood flow (in vivo
      ischemia) and at 1 h and at 5 min before sacrifice (in vitro ischemia). Controls
      received an equal amount of saline. The serum amino-transferase activities after
      24 h reperfusion were significantly reduced in the silymarin-treated group (n =
      10); ALAT 293 +/- 193 U/L, ASAT 343 +/- 229 U/L compared with the control group
      (n = 7): ALAT 1238 +/- 743 U/L, ASAT 948 +/- 541 U/L (p < 0.03), and the extent
      of necrosis decreased from 25.6 +/- 16.0% ( n = 7) to 7.8 +/- 8.3% (n = 10) (p <
      0.01) after treatment with silymarin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287123
TI  - Cellular localization of tissue factor in human breast cancer cell lines.
AB  - Expression of tissue factor (TF), the cellular receptor of clotting factor
      VII/VIIa, is a feature of certain malignant tumours. The TF gene has been
      classified as an immediate early gene responsive to serum and cytokines. Thus,
      the regulation of TF gene expression seems to play a role in cell growth.
      Recently, we have shown that constitutive TF expression in MCF-7 breast cancer
      cells is modulated by such growth factors as EGF, TGF alpha, and IL-1. The
      present study deals with the immunocytochemically detectable cellular
      distribution of TF in human breast cancer cell lines MCF-7 and MaTu stimulated by
      EGF and TGF alpha. In MCF-7 cells growing logarithmically, stimulation led to a
      significant increase of TF mRNA after 2 h (in situ hybridization, Northern blot)
      and to maximum TF expression after 6 h (immunohistochemistry). When decorated by
      monoclonal antibodies, TF protein showed a pronounced localization at ruffled
      membrane areas, cell edges, and processes of spreading cells after 6 and 20 h. In
      more flattened cells TF was concentrated in peripheric lamellae and microspikes
      communicating with neighbouring cells. After epithelial colony pattern had
      established, TF was predominantly accumulated at the intercellular boundaries.
      The vary same distribution patterns as seen in MCF-7 cells were true for the
      stimulated MaTu cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287124
TI  - Primary gastric lymphoma is rarely associated with Epstein-Barr virus.
AB  - Recently, the association of Epstein-Barr virus (EBV) with undifferentiated
      lymphoepithelioma-like carcinoma and adenocarcinoma of the stomach has been
      described. In this study of 55 primary gastric lymphomas, most of them belonging
      to the group of MALT lymphomas, the question of possible EBV involvement has been
      addressed using in-situ hybridization (ISH) and blot techniques. EBV DNA and/or
      DNA sequences were found in only two of 24 centroblastic and B-immunoblastic
      lymphomas and in one anaplastic large cell lymphoma of null cell phenotype. In a
      further centroblastic lymphoma, a few positive nontumorous (bystander) cells were
      identified by ISH. By means of ISH, no positive signals could be detected in the
      preserved overlying mucosa nor in regenerating epithelium adjacent to lymphoma
      induced ulcerations.

PMID- 8287125
TI  - Identification of p53 gene mutations in gastrointestinal and pancreatic
      carcinoids by nonradioisotopic SSCA.
AB  - A nonisotopic screening method based on single-strand DNA conformation analysis
      (SSCA) was established for the identification of p53 gene alterations in achieved
      tissue samples. The sensitivity of this approach was validated by testing
      mutations previously identified by direct sequencing. Applying this assay, 40
      samples of formalin-fixed, paraffin-embedded tumors, including 33
      gastrointestinal carcinoids and seven endocrine pancreatic tumors, were screened.
      Only one mutation (codon 283, CGC to CCC) was identified in a single clinically
      benign rectal carcinoid. This mutation occurred during the development of the
      tumor and was accompanied by loss of the wild-type gene. Our data indicate, that,
      in contrast to gastrointestinal carcinomas, alterations of the p53 gene are
      infrequent events in the development of gastrointestinal and pancreatic
      carcinoids. In addition, there was no evidence for the involvement of p53 in the
      malignant metastatic progression of carcinoids.

PMID- 8287126
TI  - Aldolase C in neuroendocrine tumors: an immunohistochemical study.
AB  - The expression of cerebral type aldolase C was investigated immunohistochemically
      in six varieties of neuroendocrine (n = 57) and six types of non-endocrine tumor
      (n = 76) using the avidin-biotin complex method. Aldolase C expression in the
      neuroendocrine tumors was also compared with those of chromogranin and gamma
      enolase. Aldolase C was detected in all the islet cell (7/7) and carcinoid tumors
      (10/10), thyroid medullary carcinomas (7/7), and pheochromocytomas (10/10), as
      well as in the majority of neuronal tumors (8/10) and bronchial small cell
      carcinomas (10/13). Chromogranin immunoreactivity was restricted to the tumors
      with abundant neuroendocrine granules. Gamma enolase positivity was generally
      similar to that of aldolase C, but there were some differences. Amongst the
      bronchial small cell carcinomas, three tumors negative for gamma enolase were
      positive for aldolase C, while another three tumors were positive for gamma
      enolase only. However all the small cell carcinomas were positive for at least
      one of these two enzymes. Aldolase C was detected in 28 (37%) of the 76 non
      endocrine tumors and tended to be expressed preferentially in the differentiated
      portions of these tumors. Although aldolase C was expressed in many bronchial
      squamous cell carcinomas, the immunoreactivity was localized mainly in
      keratinizing foci and the less differentiated parts of these tumors expressed the
      enzyme only occasionally. Thus aldolase C, in conjunction with other
      neuroendocrine-associated markers, may be of value in identifying tumors of
      neuroendocrine type.

PMID- 8287127
TI  - Juxtaglomerular cell tumor cell line producing active renin and its precursors.
AB  - We have established tumor cell lines from a rare juxtaglomerular cell tumor
      (JGCT) of the kidney. The original tumor contained both neoplastic cells and a
      tubular component. The tumor cell line (JX-G) maintained a capacity for renin
      production after the 20th passage. Cells at the fourth and 16th passage strongly
      reacted immunocytochemically with an antihuman renin antibody. Western blot
      analysis at the 9th passage revealed a positive reaction for renin at M(r) 45,000
      and M(r) 62,000 which corresponded to renin precursors. However, the total amount
      of active renin secreted into the culture medium was high in the primary culture,
      but undetectable after the 4th passage. These findings indicate that the JGCT
      cell lines produced both active and inactive renin and the primary cultured JGCT
      cells secreted active renin, but that the secretion of renin had diminished after
      several passages. Additional stimuli thus appear necessary for maturation of
      renin and its subsequent secretion. These findings and the presence of a tubular
      component in the original tumor suggest that some signal transduction system is
      maintained in JGCTs. The physiological relationship of JGCT to the
      juxtaglomerular apparatus (JGA) and possible applications of the new cell lines
      are also discussed.

PMID- 8287128
TI  - Regional appearance of atrial natriuretic peptide in the ventricles of infarcted
      rat hearts.
AB  - The appearance of atrial natriuretic peptide (ANP) in the ventricular myocardium
      was investigated in rat hearts subjected to severe left ventricular infarction.
      The left coronary artery was ligated for 1, 2, 3, 4 and 6 days and for 3 weeks,
      and the tissue was prepared for microscopic examination of immunoreactive ANP and
      for electron microscopy. In the normal and sham-operated hearts, and in hearts
      subjected to 1 day of coronary ligation, ANP immunoreactivity was restricted to a
      few ventricular myocytes of the conduction system. Following 2-3 days of coronary
      ligation, ANP immunoreactivity was detected in the viable myocardium of the
      lateral border of the infarct and in a few layers of viable cardiac myocytes
      located in the subendocardial areas of the ischemic left free ventricular wall.
      Further, during the following days and after 3 weeks of coronary ligation, a
      gradient of specific labeling was commonly seen across the lateral border area of
      the infarct. Thus, the strongest immunoreactivities were present in the cardiac
      myocytes located adjacent to the non-contracting myocardium. Electron microscopic
      examination of the immunoreactive cardiac myocytes confirmed the presence of
      electron-dense specific granules within these cells. The present findings suggest
      that the increased regional production of ANP within the ventricular myocardium
      is induced by increased mechanical stretch of the cardiac myocytes, and that this
      might contribute to the increased release of ANP in myocardial infarction.

PMID- 8287129
TI  - Effects of human epidermal growth factor on the development of bile canaliculi in
      neonatal rat hepatocytes in primary culture.
AB  - We have examined the effects of human epidermal growth factor (hEGF), a growth
      promoting factor for hepatocytes, on the cytoskeletal structure and intercellular
      contacts in neonatal hepatocytes in primary culture. The ultrastructural
      characteristics of cellular contacts and bile canaliculi (BC) were examined using
      a newly developed technique of scanning electron microscopy for cultured
      hepatocytes. The neonatal hepatocytes incubated with hEGF plus insulin for 3 h
      showed more variety in shape than controls, and their cellular contacts were very
      loose with many long fibers. At this time, there were no changes in the
      distribution of microtubules or microfilaments. After treatment with hEGF plus
      insulin for 21 h, the distribution of microfilaments was altered. Actin filaments
      no longer surrounded BC, but were observed near the cell periphery; in addition,
      DNA synthesis was increased to 3.9 times the rate in controls. Treatment with
      dexamethasone for 3 h caused tight straight cellular contacts, and after 21 h
      actin filaments appeared around slightly dilated BC, but there was no increase in
      DNA synthesis. Transmission electron microscopy showed that the transport and
      secretion of horseradish peroxidase in BC was inhibited after 3-h incubation with
      hEGF. These results suggested that hEGF first affected the cellular contacts of
      hepatocytes necessary for the development of cellular polarity, and then affected
      the distribution of actin filaments, the development of functioning BC being
      suppressed.

PMID- 8287130
TI  - Semiconductor laser-induced fluorescence detection in capillary electrophoresis
      using a cyanine dye.
AB  - Cy5, an activated carboxyl cyanine fluorophore, was characterized by capillary
      electrophoresis (CE) using a semiconductor laser at 652 nm to induce
      fluorescence. Hydrolysis of the activated Cy5 in the presence of ammonia results
      in the formation of a mono- and diamide and a dicarboxylic acid. A Cy5-labeled
      oligonucleotide M13 primer for DNA sequencing (M13mp18 template) was synthesized
      with a purity of better than 95%. The labeled primer was analyzed by liquid
      chromatography, using UV-visible detection, and by CE, monitored by laser-induced
      fluorescence (LIF) detection. Analysis of the Cy5-labeled oligonucleotide primer
      by CE-LIF in a 9% polyacrylamide gel-filled capillary indicated the purity of the
      major Cy5-oligonucleotide primer was greater than 90%. The detection sensitivity
      for Cy5-based CE-LIF detection system with a 2.5-mW red semiconductor laser is
      about 10(-10) M.

PMID- 8287131
TI  - Cetyltrimethylammonium chloride as a surfactant buffer additive for reversed
      polarity capillary electrophoresis-electrospray mass spectrometry.
AB  - The rapid analysis of picomole quantities of various cationic molecules (laser
      dyes, tripeptides and larger bioactive peptides) has been achieved by on-line
      capillary electrophoresis-electrospray mass spectrometry (CE-ES-MS). Use of the
      cationic surfactant, cetyltrimethylammonium chloride (CTAC) in the CE buffer
      greatly facilitated the analyses. Under reversed-polarity conditions (negative
      potential at the source vial), CTAC induces electroosmotic flow towards the mass
      spectrometer, presumably due to the creation of a cationic layer on the inner
      surface of the fused-silica capillaries. CTAC diminishes analyte-capillary wall
      interactions, allowing efficient separations and symmetrical peak shapes. It may
      be used over a wide range of pH values without loss of electroosmotic flow. Added
      selectivity, provided by the surfactant properties of CTAC, played a critical
      role in resolving closely related tripeptides as well as larger (five to thirteen
      amino acid units) peptides. Above the critical micelle concentration of CTAC,
      interactions with the pseudostationary micellar phase increased selectivity even
      for ionic analytes.

PMID- 8287132
TI  - Determination of peptides by capillary electrophoresis-electrochemical detection
      using on-column Cu(II) complexation.
AB  - A Cu(II)-coated capillary has been developed for the determination of peptides by
      capillary electrophoresis with electrochemical detection. Capillaries were
      prepared by forcing a solution 48 microM in CuSO4, 120 microM in tartaric acid,
      2.4 mM in NaOH and 120 microM in KI through them for 25 min; the resulting
      capillaries are stable for at least 12 h. Under alkaline conditions, peptides
      complex with Cu(II) present on the walls of the capillary to form Cu(II)-peptide
      complexes which can be detected oxidatively at a carbon fiber electrode. Di-, tri
      , tetra- and pentaglycine were determined with a detection limit of 7 x 10(-7) M
      for triglycine. N-Terminal-blocked peptides can also be determined via this
      method. This system is more sensitive than direct detection of peptides by UV at
      210 nm and exhibits higher selectivity than commonly employed derivatization
      procedures based on reactions with a primary amine functionality.

PMID- 8287133
TI  - Assessment of automated capillary electrophoresis for therapeutic and diagnostic
      drug monitoring: determination of bupivacaine in drain fluid and antipyrine in
      plasma.
AB  - In an effort to evaluate the use of electrokinetic capillary technology for
      therapeutic and diagnostic drug monitoring, samples were analysed batchwise with
      an automated, high-throughput capillary electrophoretic instrument coupled to an
      inexpensive PC data acquisition and evaluation system. Examples studied included
      the capillary electrophoretic (HPCE) determination of bupivacaine in drain fluid
      collected after pulmonary surgery and the micellar electrokinetic capillary
      chromatographic (MECC) determination of antipyrine in human plasma. Analyses for
      antipyrine could be accomplished without any sample pretreatment whereas
      bupivacaine required extraction prior to analysis. Antipyrine determination was
      effected through external calibration using either peak areas, relative peak
      areas or peak heights. The intraday and interday reproducibilities (n = 15) of
      the evaluated concentrations were 1.5-3% and 5-6%, respectively. For bupivacaine,
      determination based on internal and external calibration employing peak areas and
      peak heights was investigated. The intraday and interday reproducibilities (n =
      5) of bupivacaine concentrations were about 1% and 2%, respectively, for internal
      calibration and both about 5% for external calibration. The electrokinetic
      capillary data compared well with data obtained by gas chromatography
      (bupivacaine) and high-performance liquid chromatography (antipyrine).

PMID- 8287134
TI  - Investigation of the metabolism of the neuroleptic drug haloperidol by capillary
      electrophoresis.
AB  - Free solution capillary electrophoresis (FSCE) conditions were previously
      reported to be of limited use for the separation of pharmaceuticals, since many
      of these compounds are neutral. We show that by consideration of compound
      hydrophobicity and ionisable functional groups, FSCE conditions can be developed
      to effect the separation of a drug and its phase I metabolites. This is brought
      about by adding a suitable organic modifier to aid solubility, and modifying pH
      to effect a change in the mass to charge ratio of the metabolites present.
      Furthermore, we show that in this drug metabolism study, FSCE presents an
      advantage over both reversed-phase HPLC and micellar electrokinetic
      chromatography. We also demonstrate the use of FSCE for investigation of the
      phase I metabolites produced by the in vitro incubation of haloperidol (a
      neuroleptic agent) with both mouse and guinea pig hepatic microsomes and show
      that such an approach can be used to detect both qualitative and quantitative
      differences in species metabolism.

PMID- 8287135
TI  - Separation of estrogens and rodenticides using capillary electrophoresis with
      aqueous-methanolic buffers.
AB  - Capillary electrophoresis (CE) has proven to be an efficient method for the
      separation of various charged and neutral analytes. For analytes having limited
      solubility in water, the CE mode of separation has been micellar electrokinetic
      capillary chromatography (MECC). However, another approach is the direct addition
      of an organic solvent to a non-MECC CE separation system. Walbroehl and Jorgenson
      and also Balchunas and Sepaniak have reported on the use of organics in CE but
      the focus of their work was using MECC to separate small organic compounds. This
      work examines the use of aqueous-methanolic buffers in non-MECC CE separations of
      estrogens and rodenticides.

PMID- 8287136
TI  - Separation of gangliosides using cyclodextrin in capillary zone electrophoresis.
AB  - Gangliosides are glycosphingolipids containing sialic acid. These glycolipids
      have been suggested to play important roles in biological processes such as cell
      growth, differentiation and malignant transformation. Based on these proposed
      biological functions, gangliosides can be used as diagnostic tools and
      therapeutics for various human diseases. In this study, capillary zone
      electrophoresis (CZE) was used to determine the major gangliosides GM1, GD1a,
      GD1b and GT1b in mammalian brains, in addition to GM3 and Lac. Enhancement of
      selectivity and efficiency of separation was obtained by using 50 mM borate
      phosphate buffer containing 16.5 mM alpha-cyclodextrin (alpha-CD). Under this
      condition, several forms of gangliosides were successfully separated from
      extracts of deer antler, apricot seed and rat brain. The results demonstrate that
      the CD-modified CZE is a useful method for detecting glycolipids from various
      biological matrices.

PMID- 8287137
TI  - Screening for diuretics in urine and blood serum by capillary zone
      electrophoresis.
AB  - Diuretics are therapeutic agents used to promote the excretion of bodily fluids
      and salts. They are also misused by some athletes to decrease body mass or to
      mask the use of anabolic steroids and other drugs. We have developed a method
      that screens for diuretics in urine and blood serum. Two successive runs were
      required because of the heterogeneity of this group of compounds. Screening for
      diuretics that contained sulphonamide and/or carboxylic groups was done at pH
      10.6 with 3-(cyclohexylamino)-1-propane-sulphonic acid (0.06 M) as buffer.
      Diuretics that contained primary, secondary or tertiary amine groups were
      investigated at pH 4.5 with an acetate (0.07 M)-betaine (0.5 M) buffer system.
      Hydrostatic injection mode for 5 s gave the best efficiency. Longer injection
      times were acceptable but efficiency was then somewhat reduced. Detection limits
      at the low femtomole level are achievable for most compounds with a UV-Vis
      detector operating at 220 and 215 nm. Temperature affected the separation, and 20
      degrees C proved best. All compounds were separated in less than 30 mins. A
      confirmation analysis of all compounds was done by GC-MS.

PMID- 8287138
TI  - Determination of theophylline in plasma using different capillary electrophoretic
      systems.
AB  - Theophylline was determined in human plasma by capillary electrophoresis (CE).
      The drug was used as a model substance to study a simple sample pretreatment
      often used in HPLC: to 200 microliters of plasma were added 400 microliters of
      acetonitrile to precipitate the plasma proteins and the supernatant was injected
      into the capillary after centrifugation. Three capillary electrophoretic systems
      were compared with respect to migration time and electrophoretic migration
      reproducibility. UV detection at 280 nm was applied. The separation was
      preferably made in an uncoated fused-silica capillary (57 cm x 75 microns I.D.)
      with 10 mM phosphate-borate buffer (pH 9.0) as the electrophoretic buffer. A
      linear calibration graph was obtained in the concentration range studied, 1.8-36
      micrograms/ml (10-200 microM). The method permits the determination of
      theophylline in plasma at therapeutic concentrations of 4.5-20 micrograms/ml (25
      110 microM) with acceptable precision.

PMID- 8287139
TI  - Separation of water-soluble vitamins via high-performance capillary
      electrophoresis.
AB  - A standard sample and method for performance evaluation in capillary zone
      electrophoresis is defined. The sample, containing thiamine, nicotinamide and
      nicotinic acid, was analysed in a 20 mM sodium phosphate buffer pH 7. The impact
      of pH, buffer type and ionic strength on electroosmotic flow, electrophoretic
      mobility, and peak shape was investigated. The separation of several water
      soluble vitamins in phosphate buffer pH 7 was developed in order to analyse an
      over-the-counter vitamin preparation. Spectral analysis and peak purity tests
      were applied on-line for peak identification.

PMID- 8287140
TI  - Separation and determination of glycosaminoglycan disaccharides by micellar
      electrokinetic capillary chromatography for studies of pelt glycosaminoglycans.
AB  - Capillary electrophoresis based on cetyltrimethylammonium bromide micellar
      electrokinetic capillary chromatography (MECC) was developed for the separation
      and determination of glycosaminoglycan (GAG) disaccharide units without
      derivatization. The influence of changes in several separation conditions was
      studied, and the separation mechanisms are discussed. Tests of repeatability and
      linearity were performed for qualitative and quantitative evaluation of the
      method. The described procedure gives a rapid and efficient determination of GAG
      disaccharides. Samples of chondroitin sulphates and mink skin were treated with
      proteases, and the extent of protein cleavage was followed by free zone capillary
      electrophoresis. The result of the chondroitinase ABC treatment following the
      protease treatment was evaluated by the MECC method.

PMID- 8287141
TI  - Micellar electrokinetic capillary chromatography analysis of the behavior of
      bilirubin in micellar solutions.
AB  - The capacity factor of bilirubin is determined by micellar electrokinetic
      capillary chromatography (MECC) techniques in three different surfactant systems.
      The capacity factor of bilirubin in cholic acid, taurocholic acid, and
      taurochenodeoxycholic acid solutions are compared to each other as a function of
      pH. The pH range studied is 6.5 to 9.5 which includes the pH range of bile, and
      includes the most likely pKa values of bilirubin carboxyl groups. MECC techniques
      are used to estimate these apparent pKa values for bilirubin as well as to
      determine the capacity factors for the separate ionization states of bilirubin in
      the three different surfactants. Due to the complexity of the bilirubin-bile salt
      system, it appears as though it is not possible to use MECC to accurately
      determine the bilirubin apparent pKa values. Separations are performed in 75
      microns capillaries, typically 36 to 52 cm in length. UV detection,
      electrokinetic injection, and run voltages of 7 kV are typical. Solutions of 25
      mM of each bile salt are prepared in a 20 mM phosphate-borate buffer system.

PMID- 8287142
TI  - Use of capillary electrophoresis for monitoring citrus juice composition.
AB  - New trends in adulteration monitoring, favor the development of methods analyzing
      simultaneously as many compounds as possible. Capillary electrophoresis has been
      applied to the examination of a broad spectrum of citrus juice molecules that
      absorb in the UV and in the visible light. Depending on the conditions up to
      thirty compounds could be separated. The identified molecules included phenolic
      amines, amino acids, flavonoids, polyphenols and vitamin C. Samples can be
      analyzed without specific preparation and the best separations were obtained with
      diluted solutions due to a stacking effect. This method has been applied to the
      comparison of pure orange juice and pulpwash, a major adulterant of orange juice.
      Several significant quantitative differences were seen and it is hoped that this
      procedure will provide a more precise way of estimating pulpwash in orange juice.

PMID- 8287143
TI  - Quantitation of organic acids in sugar refinery juices with capillary zone
      electrophoresis and indirect UV detection.
AB  - During sugar refinement, monitoring of organic acids such as formate, tartrate,
      succinate, malate, glycolate and acetate in the process "juices" is important for
      process control. Matrix effects can lead to problems in conventional
      chromatographic ion analysis of these solutions. Capillary zone electrophoresis,
      with indirect UV detection, has been shown to be a good alternative, requiring
      almost no sample preparation, other than dilution, and with fast analysis time
      (less than 7 min). A co-elution problem for the formate-tartrate pair could be
      solved by adding small amounts of bivalent metal ions to the electrophoresis
      buffer. Quantitative analyses of the organic acids in the juices from beet sugar
      production and from the processing of a hydrolysed chicory root extract
      (Cichorium intybus) are reported.

PMID- 8287144
TI  - Rising trends in melanoma. An hypothesis concerning sunscreen effectiveness.
AB  - Incidence rates of melanoma have risen especially steeply since the mid-1970s.
      The two principal strategies for reduction of risk of melanoma and other skin
      cancers are sun avoidance and use of chemical sunscreens. Rising trends in the
      incidence of and mortality from melanoma have continued since the 1970s and
      1980s, when sunscreens with high sun protection factors became widely used.
      Commonly used chemical sunscreens block ultraviolet B (UVB) but are virtually
      transparent to ultraviolet A (UVA), which makes up 90 to 95% of ultraviolet
      energy in the solar spectrum. Because sunscreens prevent erythema and sunburn,
      and inhibit accommodation of the skin to sunlight, their use may permit excessive
      exposure of the skin to portions of the solar spectrum other than UVB. If
      melanoma and basal cell carcinoma are initiated or promoted by solar radiation
      other than UVB, as laboratory data suggest, then UVB sunscreens might not be
      effective in preventing these cancers, and sunscreen use might increase the risk
      of their occurrence. Alternative explanations for the rapid rise in the incidence
      and mortality rates of melanoma, such as changes in patterns of recreational sun
      exposure, are discussed. Traditional means of limiting overexposure to the sun,
      such as wearing of hats and adequate clothing and avoidance of prolonged
      sunbathing, may be more prudent than reliance on chemical sunscreens.

PMID- 8287145
TI  - Are administratively collected data useful for case-control studies?

PMID- 8287146
TI  - An important role for epidemiologists: improving administrative databases.

PMID- 8287148
TI  - Improving on a method for estimating seroprevalence from pooled sera.

PMID- 8287147
TI  - Lung cancer.

PMID- 8287149
TI  - Results of lipid and lipoprotein determination using Systeme International (SI)
      units.

PMID- 8287150
TI  - Relative risks in heart disease.

PMID- 8287151
TI  - The role of dietary fiber in the etiology of non-insulin-dependent diabetes
      mellitus. The San Luis Valley Diabetes Study.
AB  - To investigate the hypothesis that a low intake of dietary fiber could increase
      the risk of developing non-insulin-dependent diabetes mellitus (NIDDM), we
      ascertained prior dietary intake of 242 persons with known diabetes and 460
      persons without a prior diagnosis of diabetes among 20- to 74-year-old residents
      of two counties in southern Colorado from 1984 to 1986. When persons with
      diabetes were compared to nondiabetic controls, a higher reported fiber intake
      prior to diagnosis was found among persons with diabetes. A decrease in fiber of
      10 g/d was associated with a decrease in risk of NIDDM of 0.75 (95% confidence
      interval: 0.59 to 0.96), rather than an increase as hypothesized. However, when
      the diabetic group was limited to those with diabetes for less than 5 years, this
      association was no longer present. Two further analyses were carried out on 1317
      persons without a prior diagnosis of diabetes seen between 1984 and 1988. Among
      these persons, current fiber intake was inversely associated with fasting plasma
      insulin concentration. However, fiber explained less than 1% of the variation in
      fasting insulin levels. When persons with previously undiagnosed NIDDM were
      compared to normal controls, the odds ratio relating a decrease in fiber
      consumption of 10 g/d to NIDDM was 1.21 (95% confidence interval: 0.70 to 2.10)
      adjusting for calorie and carbohydrate intake. All analyses were adjusted for
      age, sex, ethnicity, and body mass index. The inconsistent findings reported here
      do not support the hypothesis that increasing dietary fiber intake could reduce
      the future occurrence of NIDDM.

PMID- 8287153
TI  - Risk factors for coronary heart disease mortality among persons with diabetes.
AB  - Although coronary heart disease is a leading cause of morbidity and mortality
      among persons with diabetes, the risk factors for coronary heart disease have not
      been well established for this population. The authors performed a case-control
      analysis by using data from two large population-based surveys. Cases of persons
      who died of coronary heart disease were identified from the 1986 National
      Mortality Followback Survey, and controls were taken from behavioral risk factor
      surveys conducted in 35 states in 1988. Diabetic women younger than 55 years with
      no other risk factors for coronary heart disease had a 16-fold higher risk of
      dying from coronary heart disease than did women without diabetes. About one
      third of younger women who died of coronary heart disease had diabetes. Diabetic
      men less than 45 years old with no other risk factors for coronary heart disease
      had an eightfold higher risk of coronary heart disease mortality. Among older
      white men and women, diabetes increased the risk of mortality from coronary heart
      disease about twofold. In younger diabetics, current cigarette smoking was
      associated with a 50% increase in risk, and high blood pressure increased the
      risk more than threefold. In the older age group, risk factors for coronary heart
      disease mortality were similar among those with and those without diabetes:
      Cigarette smoking and high blood pressure each were associated with about a
      twofold increase in risk. Diabetes is a particularly strong risk factor for
      mortality from coronary heart disease in young adults. Smoking and blood pressure
      control represent major opportunities to reduce the risk of coronary heart
      disease among persons with diabetes.

PMID- 8287152
TI  - Is there an ethnic difference in the effect of risk factors for diabetic
      retinopathy?
AB  - Mexican Americans have an increased prevalence and incidence of non-insulin
      dependent diabetes mellitus (NIDDM). In addition, Mexican American diabetic
      subjects have an increased prevalence of retinopathy relative to Caucasian
      diabetic subjects. In Mexican American diabetic subjects, established risk
      factors may have a stronger effect on diabetic retinopathy, compared to Caucasian
      diabetic subjects. In this report, we compare the effect of established risk
      factors (age at examination, gender, age at diagnosis of diabetes, duration of
      diabetes, glycemia, type of therapy, systolic and diastolic blood pressure, and
      hypertension prevalence) between Caucasian diabetic subjects (n = 478), a low
      risk population for NIDDM (Wisconsin Epidemiologic Study of Diabetic
      Retinopathy), and Mexican American diabetic subjects (n = 231), a high-risk
      population for NIDDM (San Antonio Heart Study). Retinopathy was classified into
      two categories (any or none) as assessed by seven standard stereoscopic retinal
      photographs read at the University of Wisconsin Reading Center. Mexican American
      diabetic subjects in Texas had an increased prevalence of any retinopathy (odds
      ratio = 1.71, 95% confidence interval: 1.25, 2.34), compared to Caucasian
      diabetic subjects in Wisconsin. Longer duration of diabetes, more severe
      glycemia, earlier age at diagnosis, and insulin therapy were associated with
      diabetic retinopathy in both Mexican Americans and Caucasians. Socioeconomic
      status was not associated with prevalence of retinopathy. Moreover, the effect of
      risk factors for retinopathy was similar in both ethnic groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8287154
TI  - Central adiposity and increased risk of coronary artery disease mortality in
      older women.
AB  - The relation between central adiposity, measured by the waist/hip circumference
      ratio (WHR), and 4-year risk of fatal coronary artery disease was examined in a
      large cohort (n = 32,898) of women aged 55 to 69 years. The age-adjusted relative
      risk of death from coronary artery disease (115 deaths) was 3.3 for women in the
      highest tertile of WHR compared to the lowest tertile (95% confidence interval:
      2.0, 5.6). After adjustment for age, body mass, smoking, physical activity,
      estrogen use, marital status, and alcohol intake, the relative risk of coronary
      death for women in the middle and highest tertiles versus those in the lowest
      tertile of WHR were 1.3 and 2.8, respectively (P for linear trend < 0.001).
      Further adjustment for hypertension and diabetes mellitus reduced the estimates
      slightly to 1.2 and 2.0, but the trend in relative risk remained statistically
      significant (P = 0.03). In contrast, body mass index showed no independent
      association with coronary death. Hypertension, diabetes mellitus, cigarette
      smoking, estrogen nonuse, and being unmarried were significant predictors of
      greater risk of coronary death in the multivariate model. These results indicate
      that central adiposity, reflected by an increased WHR, is an important risk
      factor for death from coronary artery disease in women, most of whom were
      postmenopausal. The association of central adiposity with risk of coronary death
      is independent, for the most part, of its association with hypertension and
      diabetes.

PMID- 8287155
TI  - Hospitalization rates for myocardial infarction among Mexican-Americans and non
      Hispanic whites. The Corpus Christi Heart Project.
AB  - The rate of hospitalization for myocardial infarction was examined in the Corpus
      Christi Heart Project (CCHP), a prospective population-based surveillance program
      in a biethnic community of Mexican-Americans and non-Hispanic whites. During 12
      months of ascertainment, a total of 740 patients hospitalized with definite (217)
      or possible (523) myocardial infarction were identified. Of the 740 subjects, 334
      were Mexican-Americans (150 females and 184 males), 348 were non-Hispanic whites
      (138 females and 210 males), and 58 were of other ethnic backgrounds. The 1-year
      age-adjusted rates of hospitalization per 100,000 population were 427.4 and 276.9
      among Mexican-American and non-Hispanic white females, respectively, and 721.4
      and 502.6 among Mexican-American and non-Hispanic white males, respectively. The
      age-adjusted hospitalization rate ratios for Mexican-Americans in relation to non
      Hispanic whites were 1.55 (95% confidence interval [CI]: 1.23 to 1.95) and 1.40
      (95% CI: 1.15 to 1.70) for females and males, respectively. These results suggest
      that Mexican-Americans may have a greater burden of coronary disease than non
      Hispanic whites.

PMID- 8287156
TI  - Factors associated with serum cholesterol level in a pediatric practice.
      Cholesterol screening in a pediatric practice.
AB  - The associations between age, sex, height, Quetelet index, blood pressure, and
      serum cholesterol level were examined among 1406 routinely screened children,
      aged 4 to 19 years, in a pediatric practice. After adjustment for sex and age,
      height and Quetelet index were associated with serum cholesterol levels. Quetelet
      index was shown by multiple linear regression to be positively related to
      cholesterol levels (b = 0.780, P < 0.01), but the predictive value of screening
      based on an elevated Quetelet index was marginal. Clustering of elevated serum
      cholesterol level, Quetelet index, and systolic blood pressure was observed.
      Familial aggregation of cholesterol levels was demonstrated using analysis of
      variance for 742 children from 342 families included in the regression analysis
      (F341,400 = 1.56, P < 0.0001). The intraclass correlation coefficient, a measure
      of familial aggregation, was 0.205 (P < 0.0001). Age, sex, height, Quetelet
      index, and familial aggregation accounted for 10.6% of the variance in serum
      cholesterol levels. Siblings of children with high cholesterol levels are a high
      yield group in cholesterol screening.

PMID- 8287157
TI  - Peripheral blood leukocyte count and respiratory symptoms.
AB  - The relationship of peripheral blood leukocyte count to respiratory symptoms was
      explored in data from the Second Annual National Health and Nutrition Survey
      (NHANES II). The study sample consisted of 9237 white and nonwhite US adults
      between the ages of 30 and 74 years. Three respiratory symptom outcomes were
      utilized: physician-diagnosed chronic cough and chronic bronchitis and self
      reported frequent wheeze apart from colds or flu in the past 12 months.
      Peripheral blood leukocyte counts were performed using a Coulter counter, model
      FN. Logistic regression analysis was performed for each of the three respiratory
      symptom outcomes controlling for age, race, gender, and cigarette-years of smoke
      exposure. The peripheral blood leukocyte count was a significant predictor for
      each symptom. For a standard deviation increase in the log leukocyte count, the
      relative odds of wheezing was 1.93 (95% confidence level [CI], 1.47 to 2.52); for
      chronic cough, 2.29 (95% CI, 1.74 to 3.00); and for bronchitis, 2.44 (95% CI,
      1.77 to 3.35). Analyses restricted to never smokers gave similar results. These
      data suggest that peripheral blood leukocyte count correlates with respiratory
      symptoms and are consistent with the hypothesis that the leukocyte count is a
      serum marker of inflammation.

PMID- 8287158
TI  - Education and mortality from cancer in Sao Paulo, Brazil.
AB  - This study investigated social class differentials in cancer mortality in Sao
      Paulo county, Brazil, for the period 1978 to 1982. A measure of socioeconomic
      status based on education was used, and cancer risk by level of education was
      estimated by a case-control approach in which other cancers were considered as
      controls. For most cancers, the socioeconomic differences in risk were similar to
      those found in western Europe and North America. For lung cancer, however, the
      highest risk was observed in men and women with the most education. Other cancers
      related to tobacco--cancer of the larynx, pharynx, and esophagus--showed a
      negative association with education. The differences between social classes in
      consumption habits of alcohol and mate and the use of black tobacco are probably
      responsible for these contrasting patterns. For breast and cervix uteri cancer
      the social class patterns were similar to those found in developed countries--a
      positive relationship for breast and a negative one for cervix uteri cancer. The
      magnitude of the differences observed between social classes for these cancers
      was frequently greater in South America than in the United States or western
      Europe.

PMID- 8287159
TI  - Level of education and change in cognitive function in a community population of
      older persons.
AB  - In a community population of persons over the age of 65, cognitive function was
      assessed using brief performance tests on two occasions 3 years apart. Those with
      fewer years of formal education consistently had greater declines in cognitive
      function, independently of age, birthplace, language of interview, occupation,
      and income. These prospective findings suggest that low educational attainment or
      a correlate predicts cognitive decline. It is not clear, however, whether this
      relation represents a direct effect of education on future cognition, whether
      education might be related to occurrence of a disease leading to cognitive
      decline in older persons, or whether education might be a surrogate for some
      variable not included in the study.

PMID- 8287160
TI  - The severity of fetal membrane infection and pregnancy complications.
AB  - The purpose of this report is to examine the association of histologic
      chorioamnionitis with microorganisms isolated from the fetal membranes and to
      evaluate whether microorganisms with or without inflammation are associated with
      labor characteristics and with pregnancy complications. Inflammation was more
      common among membranes that yielded pathogenic bacteria (47%, P = 0.002) or Urea
      plasma urealyticum (34%, P = 0.03) than among membranes that yielded no growth or
      nonpathogenic bacteria (20%). Prolonged membrane rupture (P = 0.0001), infant
      birth weight less than 2500 g (P = 0.02), and intraamniotic infection (P = 0.001)
      occurred more frequently among those women whose membranes yielded pathogenic
      bacteria than among those whose membranes yielded no growth or nonpathogenic
      bacteria. Our findings suggest that placental membranes in which pathogenic
      bacteria are accompanied by inflammation are associated with the highest risk of
      pregnancy complications.

PMID- 8287161
TI  - The use of restricted controls to prevent recall bias in case-control studies of
      reproductive outcomes.
AB  - Recall bias or report bias is said to occur when associations are distorted or
      created because case informants report events differently from controls. Some
      investigators have suggested that this bias can be prevented by choosing controls
      who have conditions similar to those found in the case group. We use the term
      "restricted-control group" for such a control series. Although using a restricted
      control series may eliminate differential misclassification, this approach will
      usually not eliminate nondifferential misclassification and may create selection
      bias. In this article, we present a way to algebraically examine the effects of
      misclassification and selection bias on observed associations. We use this method
      to compare the impact of recall bias in a study using a population control group
      with the effects of selection bias and nondifferential misclassification if a
      restricted-control group is used. Our approach is exemplified using data from a
      case-control study of sudden infant death syndrome. Our findings show that even
      when recall bias exists, the observed association can be closer to the true
      association when a population control series is used than when a restricted
      control group is used.

PMID- 8287162
TI  - C-peptide and the classification of diabetes mellitus patients in the Early
      Treatment Diabetic Retinopathy Study. Report number 6. The ETDRS Research Group.
AB  - The Early Treatment Diabetic Retinopathy Study (ETDRS), conducted at 22 clinical
      centers during the period 1980 to 1989, collected baseline data on C-peptide
      levels after ingestion of Sustacal in 582 patients with diabetes mellitus, prior
      to enrollment in the trial. Data on several clinical factors associated with
      diabetes were also collected from all 3711 enrolled patients. C-peptide data were
      used to develop sets of clinical criteria for the classification of ETDRS
      patients and to compare and contrast definitions of type of diabetes used in
      previous studies. The distribution of C-peptide levels was strikingly bimodal,
      suggesting a division of study participants into two groups--those with levels at
      80 pmol/L or less and those with more than 80 pmol/L of C-peptide after Sustacal
      ingestion. Constellations of clinical characteristics that could serve as proxies
      for C-peptide level were ascertained. The result was two sets of clinically
      developed definitions for type of diabetes in the ETDRS. According to the more
      restrictive set of definitions, three groups were identified, compared to two
      groups using the "broad" set of definitions. Discriminant analysis was also used
      to classify ETDRS patients, yielding similar results. A comparison of definitions
      of type of diabetes used in the ETDRS and in previous studies revealed that even
      in the absence of C-peptide data, clinically derived definitions provided good
      discrimination between type I and type II diabetes.

PMID- 8287163
TI  - Using administrative data for case-control studies: the case of the Papanicolaou
      smear.
AB  - Administrative data have not been used extensively for case-control studies. As
      an example, data from the Manitoba Health Services Commission were used to assess
      the effectiveness of Papanicolaou (Pap) testing in screening for cancer of the
      cervix. Case patients were 415 women with invasive cancer (aged 25 to 64 years)
      from the Manitoba Cancer Registry and control subjects were women aged 25 to 64
      years chosen from a random sample of the Manitoba female population (N = 29,926).
      For 82% of case patients there was information about Pap testing in a prior 5
      year period, as compared to 91% of the controls. Since diagnostic tests could not
      be distinguished from screening tests, data for the year prior to diagnosis were
      not used. The odds ratios for Pap testing reducing the risk of cancer of the
      cervix was 0.82 (95% confidence interval [CI]: 0.53, 1.26) for women aged 25 to
      34, 0.55 (95% CI: 0.35, 0.85) for women aged 35 to 44, 0.40 (95% CI: 0.23, 0.69)
      for women aged 45 to 54, and 0.45 (95% CI: 0.26, 0.78) for women aged 55 to 64.
      The overall 4-year relative odds adjusted for age and number of physician visits
      was 0.51 (95% CI: 0.43, 0.61). These results were similar to previously published
      values obtained from interview studies. Selection and recall bias are minimized
      and using claims avoids the expense of seeking neighborhood control subjects,
      carrying out interviews, or performing follow-up searches. As well, true
      population-based controls can be used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287164
TI  - A tribute to Edward Kass. His work on the epidemiology of urinary tract
      infections.

PMID- 8287165
TI  - From the friend of a deceased patient.

PMID- 8287166
TI  - Dutch euthanasia: background, practice, and present justifications.

PMID- 8287167
TI  - Dutch medical examiner/coroner's euthanasia report form.

PMID- 8287168
TI  - Physician attitudes and experiences with assisted suicide: results of a small
      opinion survey.

PMID- 8287169
TI  - Euthanasia: current problems in Japan.

PMID- 8287170
TI  - Reviving the swan, extending the curse of Methuselah, or adhering to the
      Kevorkian ethic?

PMID- 8287171
TI  - Bioethics here and in poor countries: a comment.

PMID- 8287172
TI  - Derek Humphry discusses death with dignity with Thomasine Kushner.

PMID- 8287173
TI  - Washington State Initiative 119: the first public vote on legalizing physician
      assisted death.

PMID- 8287174
TI  - Chinese medical ethics and euthanasia.

PMID- 8287175
TI  - CQ sources. Suicide and euthanasia.

PMID- 8287176
TI  - A small, good thing--anencephalic organ donation.

PMID- 8287177
TI  - The hastily obtained durable power of attorney: process for the sake of process?

PMID- 8287178
TI  - Been there: physicians speak for themselves.

PMID- 8287179
TI  - Pastoral care: finding a niche in ethical decision making.

PMID- 8287180
TI  - The Robinow (fetal face) syndrome: a continuing puzzle.
AB  - The history of the Robinow (fetal face) syndrome and the evolution of the
      phenotype are presented. Non-specific and syndrome-specific abnormalities are
      listed, discussed and illustrated. Existence of an autosomal dominant and an
      autosomal recessive type has been well documented. The two forms can be
      distinguished phenotypically. Hypogenitalism, especially micropenis, is a
      constant feature in males, while females show only hypoplasia of clitoris and
      labia minora and are functionally normal. No biochemical or molecular anomaly has
      been identified.

PMID- 8287181
TI  - Robinow syndrome: with special emphasis on dermatoglyphics and hand malformations
      (split hand).
AB  - Fourteen cases of Robinow syndrome are described with special emphasis on
      dermatoglyphics and hand malformations (split hands were detected in two,
      ectrodactyly with nail hypoplasia in one and hypoplastic extra middle finger in
      another one). Dermatoglyphic studies were performed on ten cases. Increased whorl
      patterns of the finger tips and a single large palmar hypothenar whorl pattern
      associated with distally displaced axial triradii were detected. These have not
      previously been described.

PMID- 8287182
TI  - Congenital heart disease and Robinow syndrome.
AB  - We present a 6-month-old infant with Robinow syndrome and tricuspid atresia (type
      Ia). Up to now, at least 67 cases of Robinow syndrome have been published
      including nine cases with a congenital heart defect (CHD). As in our case, the
      majority of the CHD were right ventricular outflow obstruction. Robinow syndrome
      with CHD is not rare and in all cases of Robinow syndrome detailed cardiologic
      evaluation and echocardiography should be performed.

PMID- 8287183
TI  - Marfanoid features and craniosynostosis: report of one case and review.
AB  - A new syndrome was delineated by Shprintzen and Goldberg (1982) based on the
      description of two patients with scaphocephaly, facial dysmorphism,
      arachnodactyly, mental retardation and other connective tissue defects. Sugarman
      and Vogel (1981) reported another child with the same overall pattern of
      anomalies. A fourth patient with normal mental development was described by
      Furlong et al. (1987) as a new syndrome. We report on another example of
      marfanoid features associated with craniosynostosis. This boy has no mental
      retardation and the case seems to be similar to the Furlong case but different
      from the others because of the lack of mental retardation.

PMID- 8287184
TI  - A third patient with median cleft upper lip, mental retardation and pugilistic
      facies (W syndrome): corroboration of a hitherto private syndrome.
AB  - We report a severely mentally retarded young male with the features of the W
      syndrome. This syndrome, to date described in only two brothers of one family, is
      characterized by severe mental retardation with seizures and a pattern of facial
      dysmorphisms including high broad forehead, down-slanting palpebral fissures,
      hypertelorism, abnormal configuration of the maxilla and mandible, peculiar nose,
      and incomplete midline oral cleft. The face has been compared to that of a boxer
      (pugilistic face). Mild skeletal anomalies have also been described. Inheritance
      is probably X-linked. The present report corroborates the existence of this
      hitherto private syndrome.

PMID- 8287185
TI  - An unusual syndrome with mental retardation and sparse hair.
AB  - We report a 16-year-old female patient with an undiagnosed syndrome, of mental
      retardation, sparse hair, a prominent lower lip, brachydactyly with cone-shaped
      epiphyses.

PMID- 8287186
TI  - Okihiro syndrome: thenar hypoplasia and Duane anomaly in three generations.
AB  - We describe a family with five members in three generations affected by Duane
      anomaly, three of whom also have minor radial ray abnormalities. This appears to
      be inherited as an autosomal dominant condition and is probably the same
      condition as that described by Temtamy et al. in 1975 and Okihiro et al. in 1977.
      One member also has congenital clubbing of the fingers and toes.

PMID- 8287187
TI  - Radial ray defect and Robin sequence: a new syndrome?
AB  - We report an infant with the principal features of bilateral radial defects, club
      foot deformity, micrognathia and cleft palate. Other dysmorphic manifestations
      include the presence of bilateral clinodactyly, medial displacement of the thumb,
      low set ears and an unusually long 2nd toe. This constellation of signs has not
      been previously reported and may constitute a new syndrome.

PMID- 8287188
TI  - Idiopathic multicentric osteolysis: family report and review of the literature.
AB  - A mother and son affected by idiopathic multicentric osteolysis are reported.
      This condition usually manifests in early childhood and is characterized by
      progressive destruction of the carpal and tarsal bones, with or without renal
      anomalies. Unusual facies might be the clinical features of the syndrome. Review
      of the literature shows that osteolysis can occur in isolation or may be
      associated with renal and/or facial anomalies.

PMID- 8287189
TI  - Syndactyly type 1 with cataracts and mental retardation.
AB  - We report a child affected by a malformation syndrome characterized by unusual
      facies, congenital cataracts, mental retardation, bilateral soft tissue
      syndactyly of the 3rd and 4th fingers and bilateral partial syndactyly of the 2nd
      and 3rd toes. The overall clinical picture in this patient is not similar to
      other cases previously reported.

PMID- 8287190
TI  - Partial 6q monosomy/partial 12q trisomy in a child with features of Kabuki make
      up syndrome.
AB  - Kabuki make-up syndrome (KMS) is a mental retardation/congenital malformation
      syndrome of unknown aetiology. We report a child with the unbalanced karyotype
      46,XY,-6,+der(6)t(6;12) (q25.3;q24.31)mat. who has several features of KMS and
      suggest a possible cause for this condition.

PMID- 8287191
TI  - Split-foot anomaly, microphthalmia, cleft-lip and cleft-palate, and mental
      retardation associated with a chromosome 6;13 translocation.
AB  - The split-hand/split-foot anomaly is a component of several disorders which may
      occur sporadically or be transmitted as autosomal dominant or autosomal recessive
      traits. We describe a severely mentally handicapped patient with ectrodactyly of
      both feet in association with extreme microphthalmia, central cleft-lip and
      palate and mental retardation. She has an apparent de novo 46,XX,t(6;13)
      (q21;q12) unbalanced translocation. Either of these breakpoints may be the locus
      for the ectrodactyly-ectodermal dysplasia-facial cleft (EEC) syndrome.

PMID- 8287192
TI  - Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in
      rat brain.
AB  - The distribution of interleukin 6 (IL-6) mRNA and IL-6 receptor (IL-6R) mRNA in
      the brain of adult male rats was studied at the light microscope level by in situ
      hybridization histochemistry using 35S-labelled oligonucleotides. The transcripts
      of both genes were localized in the pyramidal neurons and in the granular neurons
      of the hippocampus, in neurons of the habenular nucleus as well as in the
      dorsomedial and ventromedial hypothalamus, in the piriform cortex, in scattered
      neurons of the cortex and in granular cells of the cerebellum. The medial
      preoptic nucleus and the anterior tip of the lateral ventricle contained mRNA
      encoding IL-6 and its receptor. Moreover, white matter areas, such as the
      internal capsule, which consist of only fibres and glial cells, were found to
      have autoradiographic signals above background. The mRNAs for IL-6 and IL-6R in
      hippocampus and cerebellum are not different, as shown by Northern blot analyses
      of RNA isolated from these tissues. We postulate that the cytokine IL-6 is
      expressed constitutively in discrete regions of the CNS and that it is involved
      in the mechanisms coordinating metabolic, behavioural and neuroendocrine changes
      not only during illness but also under normal physiological conditions. Our
      results suggest that IL-6 mRNA and IL-6R mRNA are colocalized, thus supporting a
      role of the cytokine in autocrine and paracrine communication.

PMID- 8287193
TI  - Regional distribution of amyloid beta-protein precursor, growth-associated
      phosphoprotein-43 and microtubule-associated protein 2 messenger RNAs in the
      nigrostriatal system of normal and Weaver mutant mice and effects of ventral
      mesencephalic grafts.
AB  - Using in situ hybridization histochemistry with [32P]oligonucleotide probes, we
      studied the cellular localization of RNA transcripts for amyloid beta-protein
      precursor (beta APP), growth-associated phosphoprotein-43 (GAP-43) and
      microtubule-associated protein 2 (MAP2) in the mesostriatal system of normal
      (+/+) and weaver (wv/wv) mutant mice, which lose mesencephalic dopamine neurons.
      In addition, expression of the same messages was studied in ventral mesencephalic
      cell suspensions transplanted to the weaver striatum. Transcripts encoding GAP
      43, MAP2 and isoforms beta APP695, beta APP714 and beta APP751 were present in
      normal substantia nigra and progressively reduced in weaver substantia nigra;
      such a reduction was correlated with dopamine neuron loss. The survival of
      dopamine neurons in unilateral intrastriatal grafts was documented by
      methamphetamine-induced rotational asymmetry tests and by tyrosine hydroxylase
      immunocytochemistry. High hybridization signals were obtained for GAP-43, MAP2,
      beta APP695, beta APP714 and beta APP751 RNA transcripts in the grafted tissue;
      the beta APP770 species--normally seen in striatum and not substantia nigra--was
      not expressed in the grafts, but it was present in the recipient striatum.
      Following immunocytochemical labelling with antibodies, GAP-43 and MAP2
      immunoreactivities were seen in cell processes in the grafts and surrounding
      tissue, whereas beta APP immunoreactivity was mainly found in grafted cell
      bodies. These results suggest that the transplanted mesencephalic cells mature
      very similarly to those in the normal substantia nigra, expressing different
      mRNAs that are normally present in the ventral midbrain and which are reduced in
      the weaver mutant as a consequence of dopamine neuron loss.

PMID- 8287194
TI  - Sodium, calcium and late potassium currents are reduced in cerebellar granule
      cells cultured in the presence of a protein complex conferring resistance to
      excitatory amino acids.
AB  - Whole-cell, patch-clamp recordings were used to study voltage-gated currents
      generated by cerebellar granule cells that were cultured in medium containing
      either 10% fetal calf serum (hereafter termed S + granules) or neurite outgrowth
      and adhesion complex (NOAC, hereafter called NOAC granules). NOAC is a protein
      complex found in rabbit serum that renders granules resistant to the excitotoxic
      action of excitatory amino acids. During depolarizing commands both S+ and NOAC
      granules generated Na+ and Ca2+ inward currents and an early and a late K+
      outward currents. However, Na+ and Ca2+ inward currents and late outward K+
      currents recorded in NOAC granules were smaller than those seen in S+ granules.
      Furthermore, although of similar amplitude, early K+ currents displayed different
      kinetics in the two types of neurons. Thus, these data demonstrate that the
      electrophysiological properties of cerebellar granules, and probably of other
      neuronal populations, depend upon serum components and raise the possibility that
      an analogous modulation might be operative in vivo, and play a role in
      development, synaptic plasticity or neuropathological processes.

PMID- 8287195
TI  - Neurophysiological evidence for increased kappa opioidergic control of spinal
      cord neurons in rats with unilateral inflammation at the ankle.
AB  - The role of the endogenous kappa opioid system in the control of neuronal
      activity has been studied in the spinal cord of normal rats and in rats with
      Freund's adjuvant induced unilateral inflammation of the ankle under barbiturate
      anaesthesia. During recordings from neurons with ankle input the kappa receptor
      agonist U50,488H and/or the kappa antagonist nor-binaltorphamine were
      administered ionophoretically using multibarrel electrodes. In most neurons
      tested U50,488H reduced the responses evoked by pressure applied across the ankle
      whereas smaller proportions of neurons showed increased activity or were not
      affected. The kappa opioid antagonist nor-binaltorphamine affected more neurons
      in rats with inflammation than in control rats. Ongoing activity was increased in
      7 of 19 (37%) neurons in control rats, in 16 of 24 (67%) neurons in the acute
      phase of inflammation (2 days post inoculation) and in 15 of 23 (65%) neurons in
      the chronic phase of inflammation (16-20 days post inoculation). During
      application of nor-binaltorphamine in control rats, the responses to pressure
      were increased in 9 cells (36%), reduced in 7 cells (28%) and unaffected in 9
      cells (36%). In the acute phase of inflammation significantly more neurons (11 of
      15, 73%) showed enhanced responses to pressure during ionophoresis of nor
      binaltorphamine but not in the chronic phase. These results show that spinal cord
      neurons with ankle input are influenced by the endogenous kappa opioid system
      particularly under inflammatory conditions. The upregulation of this system under
      inflammatory conditions may serve to counteract inflammation-induced
      hyperexcitability.

PMID- 8287196
TI  - Electrical kindling of the hippocampus is associated with functional activation
      of neuropeptide Y-containing neurons.
AB  - The release of neuropeptide Y (NPY) was measured from hippocampal slices of rats
      at stage 2 (preconvulsive stage) and stage 5 (full seizure expression) of
      electrical kindling of the dorsal hippocampus (upper blade of the dentate gyrus).
      Spontaneous release in naive rats (9.0 +/- 0.8 fmol/ml every 10 min) was
      independent of external Ca2+ but was reduced by 38 +/- 3.6% (P < 0.05) during 20
      min incubation with 5 microM tetrodotoxin. Spontaneous efflux in naive rats did
      not differ from that in shams (implanted with electrodes but not stimulated) or
      in rats kindled to stage 2 and stage 5. Twenty-five, 50 and 100 mM KCl induced a
      concentration-dependent release of NPY (P < 0.05 and P < 0.01 at 25 and 50-100 mM
      respectively) from slices of shams. The effect of 100 mM KCl was reduced by 94 +/
      1% (P < 0.01) in the absence of Ca2+. Two days after the last stage 2
      stimulation and 1 week after the last stage 5 seizure, NPY release was
      significantly larger than in shams at all KCl concentrations in the stimulated
      and contralateral hippocampus (P < 0.05 and P < 0.01). Forty-eight hours after
      one single after-discharge and 1 month after the last stage 5 seizure, 50 mM KCl
      induced a significantly larger release of NPY in the stimulated and contralateral
      hippocampus (P < 0.01 and P < 0.05), although the effect was less than during
      kindling.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287197
TI  - Frequent and difficult problems perceived by nurses caring for the dying in
      community, hospice and acute care settings.
AB  - A total of 167 practising nurses from three practice settings--community, hospice
      and acute care--were asked to identify the five most common problems encountered
      when caring for the dying and the five most difficult problems to manage. Nine
      main categories of problems were elicited, including physical, work-related,
      nurse-related, death-related and spiritual problems. Key categories have been
      selected for discussion in this paper. Specific differences in the responses
      obtained from the three practice settings may be related to differences in the
      ethos of care of the dying patient in each area, particularly between
      hospice/community care and acute care. The findings of the survey will serve as a
      basis for planning initiatives in education and research in palliative care
      nursing.

PMID- 8287199
TI  - Managing family problems in advanced disease--a flow diagram.
AB  - The interaction between patient, family and professional team can sometimes make
      difficult situations worse rather than better. This flow diagram attempts to
      clarify the process by which a professional assesses situations and suggests ways
      in which people can gain understanding about their difficulties. Once everyone
      has a greater understanding of what is or is not happening, the diagram points to
      ways in which professionals can use questions to help patient and family create a
      solution that is workable both for them and for the professionals.

PMID- 8287198
TI  - Attitudes of general practitioners in Bizkaia, Spain, towards the terminally ill
      patient.
AB  - This paper reports the results of a survey of general practitioners in Biscay
      which investigated the types of narcotics used in the treatment of chronic
      malignant pain, the degree of their use and the difficulties encountered both in
      the use of narcotics and the general care of the terminally ill patient. We found
      that (1) 50% of the doctors surveyed used narcotics in the treatment of at least
      60% of their patients with terminal disease; (2) morphine is the most frequently
      used narcotic, usually being given orally, and (3) those who completed the
      questionnaire showed themselves to be highly motivated when treating terminally
      ill patients. However, they considered that their motivation exceeded their level
      of competence and, according to the majority, collaboration between the different
      health services and the formation of interdisciplinary teams would be the best
      way to facilitate an increase in competence.

PMID- 8287200
TI  - Terminal care in the community--an evaluation of residential workshops for
      general practitioner/district nurse teams.
AB  - This paper describes the development and content of palliative care residential
      workshops for general practitioner/district nurse pairs from the same practice.
      Pre- and post-testing self-rating scales were completed by the participants of
      five workshops. A retrospective questionnaire identified perceived effects on
      practice in terms of patient and family care, and the impact of having attended
      with a professional colleague. Demographic data are presented followed by
      respondents' perceived changes in practice following the workshop. These are
      supported by clinical examples. Respondents were able to identify specific
      effects of having attended with a colleague and offered supporting examples from
      their practice. The difficulties and limitations in the use of self-rating scales
      are discussed along with the possible effects of such methods on course content
      and development. Recommendations are made for further study.

PMID- 8287201
TI  - Brief social work intervention in the hospice setting: person-centred work and
      crisis intervention synthesized and distilled.
AB  - This essay explores the difficulties faced in a hospice when offering brief
      intervention work with the friends or relatives of patients. The relevance of
      various theories of intervention is explored and it is concluded that elements
      from a number of theories need to be applied flexibly when working for one or two
      meetings with people.

PMID- 8287202
TI  - Subcutaneous ketorolac--a new development in pain control.
AB  - Pain due to advanced malignant disease does not always respond to opioids, or the
      possible use of opioids may be limited by the occurrence of adverse effects. This
      paper describes the successful use of ketorolac, a new nonsteroidal anti
      inflammatory drug, given by continuous subcutaneous infusion. Seven patients with
      pain due to advanced malignant disease taking opioid analgesia were considered to
      have inadequate symptom control because of opioid unresponsiveness (n = 1),
      opioid-related adverse effects (n = 2) or both (n = 4). All patients became
      symptom-free with the introduction of ketorolac by subcutaneous infusion and the
      total daily opioid requirement was substantially reduced in three and reduced to
      zero in four patients.

PMID- 8287203
TI  - PCA pump.

PMID- 8287204
TI  - The use of octreotide in bowel obstruction.

PMID- 8287205
TI  - Use of microwaves for rapid fixation of tissues in vivo.
AB  - Accurate knowledge of the concentration in the central nervous system of
      neurochemicals undergoing rapid enzymatic destruction or synthesis is sparse
      because of the difficulty in stopping the rapid reactions while causing only
      minimal adverse changes in the neurochemistry and structure. Microwave heating
      can be effectively used to rapidly stop enzyme activity in the central nervous
      system with minimal adverse changes. This rapid inactivation of the enzymes
      increases the validity of the sample that is taken for analysis of the
      concentration of the enzyme's substrate.

PMID- 8287206
TI  - A review of rapid microwave fixation technology: its expanding niche in
      morphologic studies.
AB  - Microwave (MW) fixation methods are important because excellent preservation of
      both cell structure and antigenicity can be attained several orders of magnitude
      faster than by routine chemical fixation methods. However, because of the
      limitations of commercial MW ovens, fixation results are often irreproducible. We
      present a standardization protocol for MW fixation in household MW ovens that
      emphasizes magnetron warm-up; the use of a water load during sample irradiation,
      of an agar/saline/Giemsa model to evaluate uniformity of irradiation within the
      MW cavity, and of specimen containers with one dimension less than 1.5 cm; and
      fast specimen handling to prevent conductive heating artifacts after irradiation.
      We describe a prototypic MW device that improves the precision of sample
      irradiation and fixes blocks of tissue and cells in suspension in milliseconds.
      The solutions used to immerse the specimen during irradiation influence the
      specimen morphology. Aldehyde- or osmium-containing solutions used simultaneously
      with MW irradiation resulted in the best morphologic preservation of specimens up
      to 1 cm3. Using MW fixation methods and a postembedding, ultrastructural
      immunogold-labeling approach, we have localized granule chymase and histamine in
      rat mast cells and amylase in rat parotid acinar cells.

PMID- 8287207
TI  - Microwave techniques for diagnostic laboratories.
AB  - Microwaves (MWs) were first introduced as a method of fixation just over 20 years
      ago. In recent years their use has extended far beyond that of a safe, clean and
      rapid method of fixation of tissue blocks and large specimens, including brains.
      MWs accelerate the action of cross-linking fixatives and can greatly accelerate
      the various stages of tissue processing to produce a paraffin block in 30 min. An
      extensive range of ultrafast MW-stimulated special stains has been developed, and
      immunohistochemical procedures can be completed in 20 min by employing MWs.
      Cellular antigens are distinctly better preserved in tissues fixed by MWs than by
      conventional cross-linking fixatives. Also, the cytomorphology of cryostat
      sections irradiated in Wolman's solution is clearly improved. MWs can similarly
      be applied for fixation and staining of preparations for transmission and
      scanning electron microscopy, and they also greatly accelerate polymerisation of
      resins. In the current climate of cost containment, this wide range of
      applications makes the MW oven an invaluable addition to the diagnostic
      laboratory.

PMID- 8287208
TI  - Coronary thrombosis in non-cardiac death.
AB  - BACKGROUND: Coronary thrombosis is the major cause of acute myocardial ischaemia
      but can be, albeit rarely, clinically silent. We investigated a series of autopsy
      hearts from hospitalized patients who died from non-cardiac causes, to detect and
      study coronary thrombosis. METHODS: The series consisted of 132 autopsy cases (81
      men and 51 women, age range 32-39 years, mean 63 +/- 14), in whom cause of death
      was confirmed as extracardiac. Major epicardial coronary arteries were isolated
      from the hearts and routinely processed for histopathological study. We evaluated
      the presence of coronary atherosclerosis and thrombosis. Plaque size was
      histologically graded with low magnification lenses. RESULTS: Coronary
      atherosclerosis, which was found in 110 hearts, caused critical stenosis or
      occlusion of at least one major vessel in 55 (41.6%) cases. Coronary thrombosis
      was found in 10 vessels from nine different hearts. One coronary tree presented
      two thrombi in two different vessels. Thrombi were mural in all but one vessel.
      We did not observe either deep sub-thrombotic ulceration or atheromatous material
      mixed with thrombus. Deep thrombus layers often presented organizing features.
      There was no correlation between thrombosis and degree of vessel stenosis, which
      was only mildly increased by thrombus. Plaque rupture without thrombus was found
      in five coronary arteries of five different cases. CONCLUSIONS: Coronary thrombus
      may overlay the intima of a diseased vessel independently of plaque type and
      severity. Moreover, thrombosis is more frequent than expected, although it is
      rare when compared with the spread of coronary atherosclerosis. It may represent
      a plaque progression mechanism in the natural history of coronary
      atherosclerosis.

PMID- 8287209
TI  - Prognosis in men and women coming to the emergency room with chest pain or other
      symptoms suggestive of acute myocardial infarction.
AB  - BACKGROUND: Previous studies suggest a gender-related difference in prognosis
      among patients with ischaemic heart disease. In the present study, we aimed to
      describe the characteristics and prognosis among patients with suspected
      ischaemic heart disease in relation to gender. METHODS: During the 21 months of
      the study, all patients who came to the medical emergency room of one single
      hospital as a result of chest pain or other symptoms suggestive of acute
      myocardial infarction were prospectively followed for 1 year. RESULTS: A total of
      5362 patients were admitted on 7157 occasions; men accounted for 55% of the
      admissions. The 1-year mortality rate was 11% for men compared with 10% for
      women. The women were older and had a higher prevalence of known congestive heart
      failure and hypertension, whereas the prevalence of previous myocardial
      infarction was higher in men. When correcting for the dissimilarities in age and
      history of cardiovascular diseases, male gender appeared as an independent
      predictor of death. Development of myocardial infarction occurred in 25% of the
      men and 16% of the women (P < 0.001) during 1 year. The symptoms that brought
      patients to the emergency room were interpreted as being caused by myocardial
      infarction or myocardial ischemia in 29% of men compared with 21% of women (P <
      0.001). CONCLUSIONS: In a consecutive series of patients with chest pain or other
      symptoms suggesting acute myocardial infarction in the emergency room, male
      gender was an independent risk indicator for death during 1 year. This might be
      explained by a higher occurrence of coronary artery disease in men than in women
      in this patient population.

PMID- 8287210
TI  - Differential free-radical activity after successful and unsuccessful thrombolytic
      reperfusion in acute myocardial infarction.
AB  - BACKGROUND: Free-radical generation after successful thrombolysis in acute
      myocardial infarction may jeopardize ischaemic but viable myocardium, thus
      limiting the optimal benefits of reperfusion. METHODS: Circulating free-radical
      activity was assessed in 25 consecutive patients with acute myocardial
      infarction. Those who successfully reperfused (Group A) were compared with those
      who did not (Group B). We also compared patients who had or had not developed Q
      waves and patients with and without previous angina or myocardial infarction. All
      patients presented within 6 h of the onset of chest pain and received standard
      intravenous streptokinase therapy. Free-radical activity in serial serum samples
      collected over 72 h was measured using the percentage molar ratio (PMR) of the
      concentrations of 9,11-linoleic acid to 9,12-linoleic acid, and malonaldehyde
      concentration. RESULTS: Throughout the study period Group A (n = 11) showed
      significantly greater change in serum PMR and malonaldehyde levels compared with
      Group B (n = 14) (P < 0.01). PMR differences between the two groups were most
      pronounced at 3 and 12 h (P < 0.001). Patients with non-Q-wave myocardial
      infarction (n = 5) showed significantly greater changes in serum PMR and
      malonaldehyde levels (P < 0.01) compared with those with Q-wave infarction (n =
      20). A history of previous infarction or angina had no apparent effects on the
      changes in serum free-radical activity. CONCLUSIONS: Successful early reperfusion
      and non-Q-wave myocardial infarction are both associated with a significantly
      greater increase in the levels of markers of serum free-radical activity
      immediately after infarction. The results support present concepts of free
      radical-mediated reperfusion injury. Use of these assays may identify those
      patients who may be at risk from free-radical-mediated reperfusion injury.

PMID- 8287211
TI  - Sympathetic denervation of the epicardial border zone in the genesis of
      dispersion of refractoriness and arrhythmogenesis in a 7-day-old canine
      myocardial infarction model.
AB  - BACKGROUND: The purpose of this study was to clarify whether sympathetic
      denervation occurs in the infarcted heart and contributes to the dispersion of
      the effective refractory period (ERP) and arrhythmogenesis. METHODS: ERP was
      measured at 47 epicardial sites in 13 dogs with 7-day-old infarctions after
      proximal ligation of the left anterior descending artery. To delineate the
      sympathetic innervation, the effects of ansae subclaviae stimulation (ASS),
      norepinephrine infusion, and prazosin infusion on ERP were tested. RESULTS: The
      per cent change in ERP (delta ERP) induced by ASS was significantly lower at test
      sites where the surviving epicardial myocardial thickness (Th) was 2 mm or less
      than at those with a Th of more than 2 mm and the normal zone. Eleven out of 179
      sites (6.1%) overlying the infarct showed no ERP change after ASS. ASS
      paradoxically prolonged ERP at 29 sites (16.2%). In contrast, norepinephrine
      infusion produced a greater delta ERP in the infarct zone than in the normal
      zone. Prazosin shortened ERP at sites where ASS prolonged it, but had no effect
      at sites where ASS shortened ERP. ASS increased both the degree of ERP dispersion
      and inducibility of ventricular tachycardias or ventricular fibrillation (VT/VF),
      whereas norepinephrine increased VT/VF inducibility despite a reduction in ERP
      dispersion. CONCLUSIONS: We conclude that heterogeneous sympathetic denervation
      contributed to a prolongation and dispersion of ERP in the surviving epicardium
      overlying the infarct. Furthermore, a supersensitive response to norepinephrine
      with resultant ERP shortening and a paradoxical ERP prolongation during ASS
      caused by alpha-receptor mechanisms that may be related to increased electrical
      instability were observed.

PMID- 8287212
TI  - Exercise testing in women with chest pain: applications and limitations of
      computer analysis.
AB  - BACKGROUND: The frequent occurrence of false-positive results of standard
      electrocardiographic (ECG) treadmill exercise testing in women limits its
      diagnostic value. In men, a commercially available computer-derived treadmill
      exercise score (TES), which quantifies the exercise ECG, has been reported to
      have high diagnostic accuracy. The purpose of this study was to test TES accuracy
      in women. METHODS: We prospectively evaluated 87 middle-aged women with chest
      pain and no previous history of cardiac events who underwent exercise testing and
      coronary arteriography (Group 1). Also, in 15 young symptomatic women with mitral
      valve prolapse and 15 age- and sex-matched controls (Group 2) we compared the TES
      score with standard exercise testing. In 25 Group 1 patients, TES could not be
      evaluated because of technical reasons. RESULTS: By standard ECG criteria, 18 out
      of the 28 women in Group 1 with coronary artery disease (55%) had a false
      positive test, whereas the TES score reduced the false positives to 5 (15%, P <
      0.001). In Group 2, the false-positive rate was improved from 12 (40%) to zero
      with TES (P < 0.001). Overall specificity was thus improved from 52% to 92% by
      TES (P < 0.0001). There was a trend towards improving the positive predictive
      value (52% versus 74%) and diagnostic accuracy (57% versus 69%) (P = 0.1), but
      sensitivity and negative predictive value were not improved with TES.
      CONCLUSIONS: The treadmill exercise score improves the specificity of exercise
      ECG especially in women with mitral valve prolapse and atypical chest pain, but
      its overall utility and accuracy in women is lower than that reported in men.

PMID- 8287213
TI  - Intravascular ultrasound assessment of the balloon-expandable Palmaz-Schatz
      coronary stent.
AB  - BACKGROUND: Coronary stenting is an effective method for the treatment of acute
      coronary dissection and restenosis. In the comprehensive assessment of restenosis
      and of the complex interaction between coronary stent and vessel wall, coronary
      arteriography has significant limitations. Intravascular ultrasound as a high
      resolution tomographic imaging method is a promising tool for resolving these
      limitations. METHODS: A 3.5, 5.0 or 5.5F, 20 MHz multi-element ultrasound
      catheter was used in 27 patients who had received a Palmaz-Schatz coronary stent
      for the treatment of symptomatic coronary dissection. Intravascular ultrasound
      study was performed during routine follow-up arteriography at 3-10 months in all
      27 patients and had also been performed in four patients during stent deployment.
      Four patients with restenosis within the stent were re-investigated 3 months
      later after repeat angioplasty. RESULTS: Complete analysis of the stented
      coronary segment could be performed in 34 out of 35 studies (97%); no adverse
      effects occurred. The three layer appearance of the vessel wall was not
      discernible in most patients because of a complex and often eccentric lesion
      surrounding the stent resulting in an asymmetrical arrangement of stent
      filaments. The beginning and the end of the stent, the central strut, and the
      overlap of a double stent could be well assessed. Luminal diameters ranged from
      1.95 to 4.15 mm and cross-sectional areas from 3.83 to 10.85 mm2. Correlations
      with quantitative arteriography revealed r-values of 0.58 for diameter and 0.59
      for area. A stent-covering layer, indicative of neointima, was clearly visible in
      all patients during follow-up arteriography with a diameter of 0.10-0.95 mm (mean
      0.25 +/- 0.15 mm), which resulted in a reduction of 2-63% in the cross-sectional
      area of the vessel. This layer did not exceed a thickness of 0.4 mm in
      asymptomatic patients. CONCLUSIONS: This study demonstrates the safe and feasible
      application of intravascular ultrasound in patients with stented coronary
      lesions. Differences between the angiographic and ultrasonic measurements are
      presumably the result of the limitations of radiography in complex and eccentric
      lesions. Intracoronary ultrasound provides a unique comprehensive assessment of
      stent expansion, neointimal proliferation, and restenosis mechanisms. Thus,
      intravascular ultrasound may also have implications regarding the indication for,
      and optimal deployment of, intracoronary stents.

PMID- 8287214
TI  - Recovery of left ventricular function after acute myocardial infarction: efficacy
      of domiciliary thrombolysis in the Grampian Region Early Anistreplase Trial.
AB  - BACKGROUND: The objective was to compare the effect of thrombolytic therapy given
      either at home or in hospital on the recovery of left ventricular function after
      acute myocardial infarction. METHODS: In a randomized double-blind trial, 311
      patients with suspected acute myocardial infarction were given 30 units
      anistreplase intravenously either at home, or later, in hospital. The median time
      saving made with domiciliary thrombolysis was 130 min. All patients were admitted
      to hospital where left ventricular stroke distance was measured daily using a
      simple bedside ultrasound technique, and expressed as a percentage of the age
      predicted normal value. The last recorded inpatient stroke distance measurement
      was used to assess residual left ventricular function after recovery from
      myocardial infarction. RESULTS: The mean stroke distance in patients with
      confirmed myocardial infarction was 74% on the day of admission, rising to 83% on
      the last inpatient day; it did not change between discharge and 3 months after
      admission. For 180 patients assigned randomly to treatment within 2 h of the
      onset of symptoms, mean stroke distance was greater by 6.8% in those given active
      anistreplase at home rather than in hospital (95% confidence interval 1.0 to
      12.7%, P = 0.02), but there was no significant difference in stroke distance
      following home or hospital thrombolysis in 111 patients assigned treatment after
      that time (difference -2.0%, 95% confidence interval -8.4 to 4.5%, P = 0.54).
      CONCLUSIONS: The efficacy of thrombolytic therapy is enhanced when administered
      within 2 h of the onset of symptoms.

PMID- 8287215
TI  - Inhibition of coronary artery reocclusion after thrombolysis with an RGD
      containing peptide with no significant effect on bleeding time.
AB  - BACKGROUND: A synthetic RGD-containing cyclic peptide, TP9201, specific for the
      platelet alpha IIb beta 3 receptor complex, was tested for its ability to
      accelerate thrombolysis and prevent reocclusion in experimentally induced
      coronary artery thrombosis. METHODS: Anesthetized, open-chest dogs with occlusive
      thrombi received tissue plasminogen activator with TP9201 (113 micrograms/kg
      bolus; 2.7 micrograms/kg/min infusion, n = 7) or saline control (n = 9). RESULTS:
      A 2.8-fold increase in the duration of vessel patency from 52.7 +/- 63.7 min to
      149.1 +/- 63.7 min (P < 0.05) was observed with TP9201 treatment. The mean
      duration of vessel occlusion was reduced 2.4-fold from 172.4 +/- 81.1 min to 71.7
      +/- 63.7 min (P < 0.05). Administration of TP9201 reduced the mean time to lysis
      from 76.6 +/- 42.9 min to 54.4 +/- 42.9 min, but thrombolysis was not
      significantly accelerated. Persistent patency was observed in four out of seven
      of the treated dogs compared with none of the nine in the control group (P <
      0.05). Administration of TP9201 inhibited ex-vivo platelet aggregation stimulated
      by ADP (30 microM) or collagen (10 micrograms/ml). No thrombocytopenia or changes
      in hemodynamic parameters were observed in the treated group compared with the
      control group. Peptide TP9201 had no effect on bleeding time and the inhibitory
      effect on ex-vivo platelet aggregation was rapid and reversible. The
      pharmacodynamic half-life of TP9201 was approximately 1 h with ex-vivo platelet
      activity returning to baseline within 2 h of discontinuation of treatment.
      CONCLUSIONS: TP9201 may be an effective therapy for the prevention of re
      thrombosis after thrombolytic therapy without adversely affecting hemostasis.

PMID- 8287216
TI  - Spinal cord stimulation in angina pectoris with normal coronary arteriograms.
AB  - BACKGROUND: Patients with angina pectoris with normal coronary arteriograms, also
      known as Syndrome X (typical exercise-induced angina pectoris, positive exercise
      testing, and normal coronary arteriograms), are often difficult to treat with
      conventional forms of medical therapy. Spinal cord stimulation has been used in
      recent years for the treatment of severe angina pectoris refractory to
      conventional medical and surgical therapy in coronary artery disease. The aim of
      this study was to investigate the effects of spinal cord stimulation on angina
      pectoris with normal coronary arteriograms. METHODS: Twelve patients underwent
      five bicycle exercise tests, three tests without (control), and two tests with
      spinal cord stimulation treatment. RESULTS: The exercise tolerance of the
      patients increased (108 +/- 22 W versus 96 +/- 21 W; P < 0.001), the magnitude of
      ST-segment depression at comparable work load decreased (1.0 +/- 0.6 mm versus
      1.5 +/- 0.9 mm; P < 0.01), time to angina increased (5.4 +/- 2.2 min versus 2.7
      +/- 1.9 min; P < 0.01), and time to the appearance of ST-segment depression
      increased (3.5 +/- 1.9 min versus 2.4 +/- 1.6 min; P < 0.01). The rate-pressure
      product at maximum work load during treatment increased, compared with the
      maximum work load during the control session (28,038 +/- 6124 mmHg x bpm versus
      25,222 +/- 4519 mmHg x bpm; P < 0.05) and the comparable work load during
      treatment (28,038 +/- th 6124 mmHg x bpm versus 24,795 +/- 5022 mmHg x bpm; P <
      0.01). CONCLUSIONS: Spinal cord stimulation has beneficial effects in angina
      pectoris with normal coronary arteriograms in terms of relief of symptoms of
      angina pectoris and improvement of exercise tolerance. These effects may be
      associated with a reduction in myocardial ischemia.

PMID- 8287217
TI  - Evaluation of a new mechanical atherectomy system (TRAC) in normal canine
      coronary arteries. Transluminal Rotary Atherectomy System.
AB  - BACKGROUND: The feasibility and safety of a new mechanical atherectomy device,
      the Transluminal Rotary Atherectomy System (TRAC), for coronary application was
      examined in vivo in eight dogs. The system operates over a standard balloon
      coronary guide wire and excises and removes the atherosclerotic material in a
      single application. METHODS: The TRAC was introduced percutaneously using routine
      cardiac catheterization technique in four open-chest dogs (acute experiments) and
      in four closed-chest dogs (chronic experiments). RESULTS: Coronary angiography at
      the end of the procedure and 1-3 days later demonstrated normal coronary arteries
      without evidence of dissection, perforation, spasm, or thrombus formation.
      Macroscopic examination revealed perivascular bleeding along the treated coronary
      arteries in two out of eight dogs. Microscopic examination of these arteries
      demonstrated minimal endothelial peeling. Histology of the other coronary
      arteries demonstrated normal intact blood vessels without evidence for thrombus
      formation. CONCLUSIONS: These results demonstrate that it is feasible and
      relatively safe to introduce and operate the new TRAC mechanical atherectomy
      system in the normal coronary arteries of a beating dog heart.

PMID- 8287218
TI  - Randomized controlled trials of potentially life-saving therapies: are they
      ethical?

PMID- 8287219
TI  - Bibliography of the current world literature.

PMID- 8287220
TI  - p53 analysis in diagnostic pathology. Biologic implications and possible clinical
      applications.

PMID- 8287221
TI  - Infrequent mutation of the p53 gene in fibrous tumors of infancy and childhood.
AB  - Mutations in the p53 tumor suppressor gene occur in > 50% of human malignancies,
      but are exceedingly rare in benign tumors. The malignant potential of fibrous
      tumors of children may be unpredictable at microscopic examination. We therefore
      sought to determine whether malignant fibrous tumors could be distinguished from
      their benign counterparts by the presence of mutations in p53. We screened 27
      fibrous tumor samples from 20 young patients. Tumors were classified as benign,
      borderline, or malignant by conventional microscopic criteria. RNA extracted from
      each specimen was used as the template for reverse transcription followed by
      polymerase chain reaction (PCR) amplification, with six pairs of primers covering
      the whole coding region of the p53 gene. All PCR products were screened for the
      presence of mutations using single-strand conformation polymorphism analysis. In
      addition, PCR products encompassing exons 5-9, the sites of the most frequent
      mutations in human tumors, were sequenced directly. Both methods detected a
      single point mutation in a highly malignant tumor (malignant fibrous
      histiocytoma). The mutation was a silent one at codon 36 (CCG-CCA, Pro-Pro). We
      conclude that p53 mutations are infrequent in childhood fibrous tumors,
      consistent with previous observations of low malignant potential (< 10%) and
      better prognosis in this tumor group. Therefore, screening for p53 mutations is
      not a useful prognostic indicator in fibrous tumors with borderline pattern at
      microscopic examination.

PMID- 8287222
TI  - p53 gene mutations in medulloblastoma. Immunohistochemistry, gel shift analysis,
      and sequencing.
AB  - Medulloblastoma (MB), the most common malignant tumor of the CNS in children,
      bears a loss of the short arm of chromosome 17 in almost half of the cases. The
      tumor suppressor gene p53 is located on this chromosome and its role in the
      pathogenesis of this primitive tumor is controversial. Twenty-two MBs were
      analyzed by single-strand conformation polymorphism (SSCP) of polymerase chain
      reaction-amplified conserved exons. Fragments displaying a gel mobility shift
      were subsequently analyzed by direct sequencing. Immunohistochemistry for p53 was
      performed in all cases; three had cytogenetic analysis. Two cases (9%) were found
      to harbor a mutation: one homozygous and one heterozygous. The latter showed
      focal p53 immunostaining. None of the cases with chromosome 17p abnormality by
      cytogenetic analysis were found to have a mutation in the remaining allele. Loss
      of heterozygosity (LOH) of 17p, however, was found in four cases (one by SSCP and
      three by cytogenetic analysis). Together with the homozygous deletion in one
      case, the overall incidence of p53 allelic involvement in MB is 23%. Although LOH
      for the p53 gene may confer a selective advantage to tumor cells harboring
      mutations with dominant negative oncogenic effect, the infrequent occurrence of
      p53 mutations in face of frequent LOH for this gene supports the previously
      formulated hypothesis of a novel tumor-related locus distal to p53 on chromosome
      17p.

PMID- 8287223
TI  - Application of the p53 gene mutation pattern for differential diagnosis of
      primary versus metastatic lung carcinomas.
AB  - The p53 gene mutation pattern was used as a diagnostic marker of multiple and
      second primary lung carcinomas. Nine cases of multiple carcinoma, which were
      suspected clinicopathologically to be double or triple primary carcinomas, were
      examined for p53 protein expression by immunohistochemistry and for genetic
      abnormality of the p53 gene by polymerase chain reaction (PCR)-single-strand
      conformation polymorphism (SSCP) analysis. Nine tumors from four cases gave a
      positive result upon both immunostaining for the p53 protein and PCR-SSCP
      analysis of the p53 gene. These nine tumors showed different mobility shifts
      between exons 5 and 8. The four cases were diagnosed genetically as multiple
      primary carcinomas. To confirm the results of PCR-SSCP analysis, five tumors from
      two cases that showed different mobility shifts were further analyzed for their
      nucleotide sequences, and it was found that all of them had point mutations at
      different codons in exons 5 and 8. These findings suggest that the p53 gene
      mutation pattern is an effective marker for diagnosis of tumor multiplicity.

PMID- 8287224
TI  - Accumulation of p53 protein as an indicator for p53 gene mutation in breast
      cancer. Occurrence of false-positives and false-negatives.
AB  - Accumulation of p53 protein resulting in levels detectable by
      immunohistochemistry (IHC) has been proposed as an indicator of mutation of the
      p53 gene. We have investigated a panel of 23 fresh-frozen breast cancers by IHC
      (PAb 1801), Southern and Northern blot analysis, and direct sequencing of the
      mutation hot spot regions (exons 5-8) of the p53 gene. Three tumors (13%) showed
      an intense nuclear staining in the majority of malignant cells, but only one of
      these showed a mutation of the p53 gene (codon 237, Arg to His). Furthermore, a
      mutation (5-bp deletion) was identified in a tumor that showed no p53
      immunoreactivity. Our results indicate that accumulation of p53 protein, as
      detectable by IHC, is not a reliable indicator for p53 gene mutation in human
      breast cancer.

PMID- 8287226
TI  - Analysis of chromosome aneuploidy in ovarian dysgerminoma by flow cytometry and
      fluorescence in situ hybridization.
AB  - We determined the DNA ploidy and the centromeric copy number of chromosomes 7,
      12, 18, and X in four cases of ovarian dysgerminoma using DNA flow cytometry and
      fluorescence in situ hybridization (FISH) with chromosome-specific alpha
      satellite probes. The analyses were performed on nuclei isolated from paraffin
      embedded tissue. The DNA index of the tumors ranged from 1.75 to 2.08 (near
      tetraploid). The FISH analysis demonstrated five copies of chromosome 7 and four
      copies of chromosome 12 in most tumors. The copy number of chromosome 18 ranged
      from two to four. The X chromosome was present in three copies in most tumors.
      These data show that the aneuploidy profile of dysgerminoma is similar to that of
      testicular seminoma. Overrepresentation of chromosomes 7 and 12 and under
      representation of chromosome 18 are characteristic cytogenetic features of
      seminoma. Seminoma and dysgerminoma share the same chromosomal marker, an
      isochromosome i(12p). Our data suggest that these tumors are also characterized
      by a similar, nonrandom pattern of chromosome gains and losses.

PMID- 8287225
TI  - Determination of B-cell clonality in paraffin-embedded lymph nodes using the
      polymerase chain reaction.
AB  - Formalin-fixed, paraffin-embedded tissue from B-cell malignant lymphomas (26),
      reactive lymphadenopathies (8), non-B-cell malignancies (5), and atypical
      lymphoproliferative lesions (7) were analyzed for clonal immunoglobulin heavy
      chain gene rearrangement by the polymerase chain reaction (PCR), using consensus
      primers for the variable and joining regions of the gene. By employing a high
      resolution gel electrophoresis technique, we were able to demonstrate one or two
      dominant bands, indicating a clonal population, in 15 of the 23 cases (65%) of B
      cell lymphoma in which amplification occurred. Six of six reactive lymph nodes in
      which amplification occurred produced a multi-banded pattern indicative of a
      polyclonal population. This improved PCR technique allows a clearer distinction
      between clonal and polyclonal patterns than other previously proposed methods. It
      also works well in paraffin-embedded tissue and may therefore be a useful adjunct
      to the diagnostic armamentarium applied to archival material.

PMID- 8287227
TI  - Disseminated persistent lymphoid hyperplasia containing Epstein-Barr virus and
      clonal rearrangements of DNA.
AB  - We describe the pathologic, molecular, and clinical features of a 52-year-old man
      who had a 7-year history of widely disseminated, persistent lymphoid hyperplasia.
      Exuberant follicular and interfollicular lymphoid hyperplasia with some
      histologic features of Castleman's disease were present at various times in the
      submental and cervical lymph nodes, lacrimal and parotid glands, right and left
      orbits, mediastinum, and hard palate of this patient. Flow cytometric and
      immunoperoxidase studies of two of the specimens indicated a slight predominance
      of cells expressing lambda-immunoglobulin light chain. In one specimen, there
      were clonal rearrangement of DNA coding for immunoglobulin heavy chain and for
      the T-cell beta-receptor. When DNA from this specimen was also examined by the
      polymerase chain reaction technique, Epstein-Barr viral DNA was detected. This
      case suggests that Epstein-Barr virus may be associated with an unusual form of
      aggressive and persistent lymphoid hyperplasia that contains clonal
      rearrangements of DNA.

PMID- 8287228
TI  - EWS rearrangement in Ewing's sarcoma and peripheral neuroectodermal tumor.
      Molecular detection and correlation with cytogenetic analysis and MIC2
      expression.
AB  - The translocation t(11;22)(q24;q12) can be identified in its classical or variant
      form in approximately 90% of cases of Ewing's sarcoma (ES) and peripheral
      neuroectodermal tumor (PNET). In this tumor group in which the histopathologic
      diagnosis is often one of exclusion, the cytogenetic demonstration of this
      translocation has become an invaluable positive diagnostic marker. With the
      recent cloning of the breakpoint regions of the t(11;22), molecular genetic
      approaches to the detection of this translocation have become possible. By
      Southern blotting, the position of the breakpoints on chromosome 22 has been
      found to be tightly clustered within a 7-kilobase (kb) fragment of the genomic
      DNA, within a gene designated EWS. In the present study, we examined the efficacy
      of an EWS complementary DNA (cDNA) probe in detecting the t(11;22) in Southern
      blots of EcoRI- or HindIII-digested DNA extracted from cases of ES and PNET. We
      also compared the results of the molecular and cytogenetic analysis with the
      expression of the ES cell surface antigen MIC2, as demonstrated by
      immunoperoxidase staining with the monoclonal antibodies O13 and HBA71. Twenty
      three specimens were studied, including 18 ES and five PNET. Of 16 cases with
      clonally abnormal karyotypes, 14 (88%) showed a typical or variant t(11;22).
      Rearrangements were demonstrated within the EWS gene with the EWS cDNA probe in
      20 of 23 specimens (87%), including all of the 14 cases, as well as in one case
      that displayed clonal numerical chromosome abnormalities only. The MIC2 antigen
      was expressed in 19 of 20 cases (95%), including all three cases lacking EWS
      rearrangement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287229
TI  - dbl oncogene expression in childhood tumors and tumor cell lines.
AB  - We studied the expression of the dbl oncogene in the total RNA obtained from a
      wide spectrum of childhood tumors, including Ewing's sarcomas, peripheral
      neuroectodermal tumors (PNET), esthesioneuroblastomas, neuroblastomas,
      retinoblastomas, rhabdomyosarcomas, osteosarcomas, and synovial sarcomas.
      Material was obtained from primary tumors, nude mice xenografts, and tumor cell
      lines. Following the Northern blot technique, a single band of 2.8 kb was found
      in each analyzed case. Induction of neural differentiation in Ewing's sarcoma,
      peripheral PNET, and neuroblastoma cell lines with dibutyryl cyclic AMP did not
      change the expression of the dbl oncogene. We conclude that the wide expression
      of the dbl oncogene in these childhood tumors reduces its value as a molecular
      marker for their differential diagnosis; on the other hand, the dbl oncogene does
      not appear to be an essential molecular factor in the process of neuroectodermal
      differentiation of small round cell tumors of childhood.

PMID- 8287230
TI  - Sporadic amplification of the MYC gene in human osteosarcomas.
AB  - The MYC proto-oncogene has been shown to be overexpressed in several types of
      sarcomas, including some osteosarcomas. In most cases, the overexpression is due
      to gene amplification. The total number of osteosarcoma patients studied,
      however, remains too small to derive any conclusions regarding the true
      prevalence and the possible clinical significance of MYC gene amplification. To
      address the issue more thoroughly, we studied 27 specimens from 25 patients with
      high-grade osteosarcoma (16 primary, 11 metastatic; 11 adult, 14 pediatric) for
      MYC gene alterations by Southern blot analysis. Two of 27 specimens (7%) showed
      MYC gene amplification: a primary fibrohistiocytic osteosarcoma of the femur in a
      37-year-old man showed threefold amplification, and a primary Paget's
      osteosarcoma of the tibia in a 60-year-old man showed fourfold amplification.
      None of the specimens tested showed MYC gene rearrangement (zero of 27) or
      activating point mutations at the PvuII site in MYC exon-1 (zero of 26). Hence,
      the MYC gene is amplified in a subset of osteosarcomas. The possible clinical or
      biological significance of MYC gene amplification in osteosarcoma may warrant
      further investigation.

PMID- 8287231
TI  - Applied molecular genetics in the diagnosis of malignant non-Hodgkin's lymphoma.
AB  - Molecular DNA analysis has contributed to our understanding of
      lymphoproliferative disorders and aids the diagnosis of complicated lymphoma
      samples. The Southern blot procedure, still the gold standard for molecular
      genetic confirmation of clonality and lymphocyte lineage, is challenged by the
      simple and time-saving polymerase chain reaction (PCR) approach, which requires
      only small amounts of DNA and works for paraffin-embedded tissues. The
      effectiveness of PCR in rearrangement analyses of T-cell receptor gamma and
      immunoglobulin heavy chain genes is well documented. Though high sensitivity is
      achieved with the PCR-based detection of the t(14;18) translocation, more
      elaborate analyses of the other rearranging immune receptor genes and of
      translocations t(11;14) and t(8;14) require the Southern blot technique.
      Detection of bcl-2, bcl-1, and c-myc gene translocation goes beyond the
      assessment of clonality or lineage; these abnormalities may help to recognize the
      cellular compartment from which the tumor lymphocytes originate or, in the case
      of c-myc, may have prognostic impact. Molecular genetics bears the potential to
      identify new criteria for lymphoma diagnosis in conjunction with cytomorphology
      and immunophenotyping.

PMID- 8287233
TI  - Correlation of viral infection, histology, and mortality in immunocompromised
      patients with pneumonia. Analysis by in situ hybridization and the polymerase
      chain reaction.
AB  - The purpose of this study was to determine the occurrence and histologic
      correlates of viral infections in immunocompromised patients with pneumonia. Of
      the 44 immunocompromised patients studied, 37 had AIDS. Lung tissue from these
      patients, including 34 with pneumocystis pneumonia, was evaluated by in situ
      hybridization for the presence of cytomegalovirus (CMV), adenovirus, Epstein-Barr
      virus, and herpes simplex virus. Fifteen of the 44 patients were positive for at
      least one virus (34%); CMV (13 cases) was the most common. In an additional seven
      cases, CMV DNA was detected using the polymerase chain reaction (PCR), for an
      overall viral detection rate of 22 of 44 (50%). Histologic features were
      diagnostic of a viral infection in nine of 15 cases (60%) of the in situ positive
      cases and in nine of 22 (41%) of the tissues where viral DNA was detected by PCR.
      Mortality rate was significantly correlated with viral detection: 77% for the
      viral-positive cases and 27% for the viral-negative cases (p < 0.05). We
      concluded that in immunocompromised patients with pneumonitis, the detection of
      viral DNA is strongly correlated with survival and that histologic features of
      the inflamed lung tissue are a specific but insensitive means of diagnosing viral
      presence.

PMID- 8287232
TI  - HTLV-I sequence in lymphoproliferative disorders.
AB  - Several recent studies reported the detection of partially deleted HTLV-I
      provirus in biopsies of lesions from patients with mycosis fungoides (MF) and T
      cell anaplastic large-cell lymphoma. We studied lesions from 59 patients (21 B
      cell lymphomas: 16 diffuse and five follicular; 11 cutaneous T-cell lymphomas,
      including seven MF; one T-immunoblastic lymphoma; 10 diffuse anaplastic large
      cell lymphomas: two B, four T, and four of indeterminate phenotype; three
      Hodgkin's lymphomas; eight atypical lymphoid proliferations; four other lymphoid
      lesions, and one squamous-cell carcinoma) using primers to the gag, pol and pX
      regions of HTLV-I in the polymerase chain reaction (PCR) to detect relevant
      sequences. A total of 10 patients showed one or more PCR-amplifiable products,
      including five of 11 patients with cutaneous T-cell lymphomas (45%) as compared
      with one of 21 patients with B-cell lymphomas (4.3%). We did not find a high
      incidence of positivity in anaplastic large-cell lymphomas, as reported
      previously. Detectable HTLV-I sequences were not limited to any subtype of
      lymphoma, and a pX sequence was detected in a squamous-cell carcinoma. Sequence
      analysis of one amplified product from each of the three regions studied showed a
      94.2, 100, and 98.9% homology to the corresponding prototypical gag, pol, and pX
      HTLV-I sequences, respectively, indicating that the amplified sequences were
      derived from HTLV-I or a very closely related virus. HTLV-I sequences were
      detected in a significant proportion of patients with cutaneous T-cell lymphoma,
      but their role in the pathogenesis of the neoplasm is still unclear.

PMID- 8287234
TI  - Simulated ischemia does not protect against efferent sympathetic denervation
      following acute myocardial infarction in canine hearts.
AB  - INTRODUCTION: Preconditioning the myocardium with brief episodes of ischemia
      preserves efferent autonomic responsiveness of noninfarcted myocardium apical to
      a site of acute transmural ischemia by mechanism(s) still unknown. We
      hypothesized that repeated brief exposure of the myocardium to a simulated
      ischemic milieu including hypoxia, high K+, low pH, and adenosine would be as
      effective as brief coronary occlusions in creating this protection. METHODS AND
      RESULTS: Open chest anesthetized dogs received an extracorporeal bypass between
      the left carotid artery and a diagonal branch of the left anterior descending
      coronary artery. We analyzed the effects of simulated ischemia on the time course
      and extent of efferent sympathetic denervation during a subsequent 3-hour
      sustained ischemia in three groups of dogs: two groups of dogs underwent four
      cycles of 5-minute intracoronary perfusion with either hypoxic altered Tyrode's
      solution (12 mM K+, 6.8 pH, and 10 microM adenosine; n = 11) or normal Tyrode's
      solution (n = 11). Each Tyrode's perfusion was separated by 5 minutes of blood
      perfusion prior to permanent coronary occlusion by latex embolization of the
      cannulated coronary artery. A third group received a continuous 3-hour blood
      perfusion before the final ischemic episode (n = 5). Shortening of effective
      refractory periods (ERPs) induced by bilateral ansae subclaviae stimulation (2 to
      4 Hz) basal and apical to the intervention site was determined before and after
      perfusions and 20, 60, 120, and 180 minutes after sustained occlusion. In all
      groups, sympathetically-induced ERP shortening was unchanged at basal sites
      throughout the experiment. ERP shortening at apical sites was unchanged after
      perfusions with either the altered or normal Tyrode's solution or after a
      continuous 3-hour blood perfusion. However, ERP shortening became significantly
      attenuated at apical sites after coronary occlusion in all groups. Neither the
      size in reduction of sympathetically-induced ERP shortening at apical test sites
      nor the cumulative percentage of denervated apical test sites (< or = 2-msec
      shortening) during a 3-hour period of permanent ischemia differed significantly
      among groups (P = 0.052 and P = 0.752, respectively). The degree of subepicardial
      involvement in the myocardial infarction was comparable among groups. CONCLUSION:
      Thus, brief exposure of the left ventricular myocardium to ischemic metabolites
      prior to a subsequent permanent coronary occlusion does not trigger mechanism(s)
      that are responsible for protection against efferent sympathetic denervation
      apical to an area of transmural myocardial infarction/ischemia.

PMID- 8287235
TI  - On the mechanism of inhibition of KATP channels by glibenclamide in rat
      ventricular myocytes.
AB  - INTRODUCTION: The mechanism by which glibenclamide inhibits KATP channel activity
      has been examined in membrane patches from isolated rat ventricular cells.
      METHODS AND RESULTS: Inside-out patches were exposed to zero, or low, [ATP] to
      activate KATP channels. Glibenclamide did not affect single channel conductance,
      but reversibly reduced channel open probability from either side of the membrane.
      Internal (cytoplasmic) glibenclamide inhibited with half-maximal inhibitory
      [glibenclamide] = 6 microM, Hill coefficient = 0.35. Complete channel inhibition
      was not observed, even at 300 microM [glibenclamide]. The response to step
      increases of internal [glibenclamide] could be resolved into two phases of
      channel inhibition (t1/2,fast < 1 sec, t1/2, slow = 10.5 +/- 0.9 sec, n = 8).
      Step decrease of [glibenclamide] caused a single resolvable phase of reactivation
      (t1/2 = 20.4 +/- 0.7 sec, n = 16). Channel inhibition by internal glibenclamide
      could be relieved by ADP, but only in the presence of Mg2+. CONCLUSION:
      Glibenclamide can inhibit KATP channels from either side of the membrane, with
      block from one side being competitive with block from the other. Internal MgADP
      antagonizes the blocking action of glibenclamide. Glibenclamide inhibition of
      cardiac KATP channels differs quantitatively and qualitatively from the
      inhibition of pancreatic KATP channels.

PMID- 8287236
TI  - Drug-induced afterdepolarizations and triggered activity occur in a discrete
      subpopulation of ventricular muscle cells (M cells) in the canine heart:
      quinidine and digitalis.
AB  - INTRODUCTION: Oscillations of membrane potential that attend or follow the
      cardiac action potential and depend on preceding transmembrane activity for their
      manifestation are known as afterdepolarizations. Early afterdepolarizations
      (EADs) interrupt or retard repolarization of the cardiac action potential,
      whereas delayed afterdepolarizations (DADs) arise after full repolarization. EADs
      and DADs can give rise to spontaneous action potentials or triggered activity
      believed to be responsible for a variety of cardiac arrhythmias. Recent studies
      from our laboratory have highlighted differences in the electrophysiology and
      pharmacology of three functionally distinct myocardial cell types found in the
      canine ventricle. Epicardial, M region, and endocardial tissues and cells show
      distinct, sometimes opposite, responses to a variety of drugs, including those
      capable of inducing EADs and DADs. METHODS AND RESULTS: In the present study, we
      used standard microelectrode techniques to examine the pharmacologic response of
      these cellular subtypes to therapeutic levels of quinidine and toxic levels of
      digitalis. Quinidine readily produced prominent EADs and EAD-induced triggered
      activity in tissue preparations from the M region (deep subepicardium), but not
      in those from epicardium, endocardium, or deep subendocardium of the canine
      ventricle. Acetylstrophanthidin produced prominent DADs in M cell preparations
      and subendocardial Purkinje fibers but only minute DADs, if any, in epicardium,
      endocardium, or deep subendocardium. DAD-induced triggered activity was observed
      to arise only in Purkinje and M cells and never in myocardial tissues from the
      epicardial, endocardial, or deep subendocardial regions of the ventricular wall.
      CONCLUSION: We conclude that EADs, DADs, and triggered activity caused by
      therapeutic levels of quinidine and toxic levels of digitalis are limited to or
      much more readily induced in a select population of cells in the deep
      subepicardial (M cell) region of the canine ventricle in addition to the Purkinje
      system of the heart.

PMID- 8287237
TI  - The substrate for atrioventricular "nodal" reentrant tachycardia: is there a
      "third pathway"?

PMID- 8287238
TI  - Molecular biology of the voltage-gated potassium channels of the cardiovascular
      system.
AB  - K+ channels represent the most diverse class of voltage-gated ion channels in
      terms of function and structure. Voltage-gated K+ channels in the heart establish
      the resting membrane K+ permeability, modulate the frequency and duration of
      action potentials, and are targets of several antiarrhythmic drugs. Consequently,
      an understanding of K+ channel structure-function relationships and pharmacology
      is of great practical interest. However, the presence of multiple overlapping
      currents in native cardiac myocytes complicates the study of basic K+ channel
      function and drug-channel interactions in these cells. The application of
      molecular cloning technology to cardiovascular K+ channels has identified the
      primary structure of these proteins, and heterologous expression systems have
      allowed a detailed analysis of channel function and pharmacology without
      contaminating currents. To date six different K+ channels have been cloned from
      rat and human heart, and all have been functionally characterized in either
      Xenopus oocytes or mammalian tissue culture systems. This initial research is an
      important step toward understanding the molecular basis of the action potential
      in the heart. An important challenge for the future is to determine the cell
      specific expression and relative contribution of these cloned channels to cardiac
      excitability.

PMID- 8287239
TI  - Sotalol.
AB  - Sotalol causes noncardioselective beta-adrenergic antagonism and prolongation of
      repolarization of cardiac tissues (Class III electrophysiologic action). This
      dual pharmacologic profile confers unprecedented antiarrhythmic properties to the
      drug. Sotalol is highly bioavailable when administered orally in the fasting
      state and is mostly cleared unchanged in the urine with an apparent half-life of
      elimination of 15 to 17 hours. It has been found effective in the suppression of
      nearly all cardiac arrhythmias, with the exception of those precipitated by
      prolongation of ventricular repolarization. Its safety and efficacy relative to
      other antiarrhythmic drugs need to be examined more fully in randomized
      controlled trials of unselected patients. The adverse effects potentially
      associated with the use of sotalol are those commonly observed with beta
      adrenergic blockade, as well as those resulting from excessive prolongation of
      the QT interval. The occurrence of torsade de pointes during treatment with
      sotalol may be minimized by limiting doses to no more than 640 mg/day and by
      strictly avoiding the development of hypokalemia.

PMID- 8287240
TI  - Rapid inward current in ischemically-injured subepicardial myocytes bordering
      myocardial infarction.
AB  - INTRODUCTION: To determine if collagenase-dispersed epicardial myocytes overlying
      myocardial infarction reproduce the same altered electrophysiology observed in
      intact epicardium, multicellular tissue preparations and enzymatically-dispersed
      myocytes from ischemically-injured canine subepicardium were examined 1 and 4
      days after myocardial infarction. METHODS AND RESULTS: The electrophysiologic
      changes observed with ischemic injury in enzymatically-dispersed myocytes were
      not different from changes observed in multicellular tissue preparations at 1 and
      4 days postinfarction. Ischemically-injured myocytes were depolarized versus
      normal myocytes at [K0]+ (2.5 to 40 mM) with reduced membrane potentials also
      observed in injured subepicardial tissue preparations [K0]+ (4 to 24 mM). On day
      1, the reduced Vmax and the prolonged recovery of Vmax from inactivation were
      consistent with the reduced membrane potentials observed at each [K0]+. The half
      maximal Vmax, maximal Vmax, and Boltzmann constant (k) in injured myocytes were
      unchanged versus normal myocytes. On day 4 postinfarction, the half-maximal Vmax
      was shifted to a more negative membrane potential, the maximal Vmax was reduced,
      and k was increased in injured versus normal myocytes. Prolonged recovery from
      inactivation was observed with depressed membrane potentials in injured myocytes
      on day 4. CONCLUSION: Enzymatically-dispersed myocytes from ischemically-injured
      subepicardium closely reproduce altered cellular properties observed in
      multicellular tissue preparations. The data suggest that 1 day postinfarction,
      altered conduction and refractoriness largely result from a reduced membrane
      potential. At 4 days, a reduced maximal Vmax, a shift in the inactivation curve
      to more negative voltages, and prolonged recovery of Vmax from inactivation also
      contribute to slowed conduction and prolonged refractoriness.

PMID- 8287241
TI  - [Counseling role of district nurses and district assistant nurses. A descriptive
      and evaluative study of the extent and intensity of counseling].
AB  - In nursing literature no consensus exists on the phenomenon 'counseling'. A
      literature search of the concept 'counseling' makes clear that it is possible to
      distinguish two dimensions of the concept 'counseling', namely 'range' and
      'intensity' of counseling. These two dimensions are the starting point of this
      study. The main purpose of this study is to gain insight in the range and
      intensity of the counseling given by district nurses and district assistant
      nurses. This article aims to discover how often psychosocial nursing problems are
      recognized and how often nursing interventions are executed by nurses, and with
      how many patients this was done. The research is designed as a secondary
      analysis. We used data collected by Wiersma et al. (1991). The results confirm
      earlier research but also offer new points of view. The study confirms that
      counseling is an essential aspect of district nursing. Some (significant)
      differences were discovered between district nurses and district assistant nurses
      in the psychosocial care that was given. Factors like level of education, patient
      population and organization will probably explain the differences between the two
      professional groups. This aspect of the study needs further inquiry.

PMID- 8287242
TI  - [Factors influencing nurses' pain assessment in children and the choice of pain
      relieving interventions].
AB  - This article reports on a qualitative study, that explored factors influencing
      nurses' pain assessment and interventions with children. Although many factors
      appear to influence decision-making processes, nurses seem to attach more weight
      to some factors than to others. For example, medical diagnosis and the intensity
      with which the child expresses its pain are used as determining factors for the
      decision to administer analgesics. In this article the results of the study,
      their relationship to information reported in the literature as well as their
      implications for practice and research are further elaborated and discussed.

PMID- 8287243
TI  - [Nursing diagnosis in deaf patients in psychiatry].
AB  - The purpose of the study was to identify NANDA-nursing diagnoses with psychiatric
      patients who are deaf or hard of hearing. The research study took place at the
      VIA (Visual Interaction Ward) of the Robert Fleury Stichting at Leidschendam. By
      means of focused interviews with nurses data were gathered from which, using
      content analysis, nursing diagnoses were identified. These diagnoses, consisting
      of defining characteristics and related factors, were reviewed on their validity
      by the nurses who take care of these patients. In this way an inventory was made
      up of the diagnoses most characteristic of the population. From the data, the
      diagnosis of impaired communication related to deafness was generated by the
      researchers themselves. Although this diagnosis is not mentioned in literature,
      it was supported by the respondents who participated in the study.

PMID- 8287244
TI  - [When is continuing education useful? A literature analysis of determinants for
      behavioral change in nurses who finished continuing education].
AB  - Nursing continuing education programmes may differ in the extent in which they
      affect nursing practice. Differences may be explained by: background
      characteristics of the participant; characteristics of the programme itself;
      characteristics of the teacher(s); characteristics of the relationship between
      the participant and the teacher(s); characteristics of the relationship between
      the participant and the other participants; characteristics of the social system;
      knowledge, skills and attitudes; and intention of the participant to change
      behavior. In this literature review, a model is presented in which these
      variables are integrated and which may be used to explain why continuing
      education programmes have no, little or much effect. On the basis of the present
      scientific knowledge, support from colleagues, supervisors and administrators (a
      characteristic of the social environment) emerges as a very important determinant
      of positive behavior changes in nursing practice.

PMID- 8287245
TI  - [District nursing and care of AIDS patients].

PMID- 8287247
TI  - In defence of the medical media.

PMID- 8287246
TI  - The mischief in the media.

PMID- 8287248
TI  - Should the NHS fund infertility services?

PMID- 8287249
TI  - Prenatal diagnosis and correction of congenital heart defects.
AB  - The improvement in heart scanning expertise during the routine obstetric scan has
      resulted in more congenital heart disease being recognized prenatally. Early
      diagnosis of severe heart malformation results in the majority of parents
      choosing to interrupt the pregnancy or allows the mother to give birth in a
      centre with obstetric and paediatric cardiac facilities.

PMID- 8287250
TI  - Fetal limb gangrene from incarceration in a dehiscent uterine perforation scar.

PMID- 8287251
TI  - Catheter treatment of congenital heart disease.
AB  - Over the last 10 years, several advances have been made in paediatric cardiology
      and cardiac surgery. However, the major developments have been in non-surgical
      attempts at transcatheter treatment of congenital heart disease. Initially these
      concerned some simple defects such as pulmonary valve stenosis but lately much
      more high-risk and complex defects have been treated.

PMID- 8287252
TI  - Laparoscopic hysterectomy: a valid alternative to conventional surgery.
AB  - According to the records of the Royal College of Obstetricians and Gynaecologists
      (1990) more than 80,000 hysterectomies were performed in the UK during 1990.
      Minimally invasive procedures are replacing conventional hysterectomies in ever
      increasing numbers. This article describes the techniques and considers whether
      the trend is a welcome one.

PMID- 8287253
TI  - Clinical use of antineutrophil cytoplasmic antibodies.
AB  - Antineutrophil cytoplasmic antibodies (ANCAs) are found in sera from patients
      with vasculitis and less commonly in sera from other autoimmune diseases. ANCAs
      provide the only specific diagnostic test for vasculitis and are also useful in
      monitoring disease activity. The indirect immunofluorescence test remains the
      best screening test for ANCAs.

PMID- 8287254
TI  - The importance of words.
AB  - It is not only the advice the doctor gives which is important--the actual words
      he uses are important too. This, the sixth article in the specialist consultation
      series, outlines how to break the good or bad news.

PMID- 8287255
TI  - Legal implications of medical research.

PMID- 8287256
TI  - Systemic hazards of ocular timolol.

PMID- 8287257
TI  - Decision making in surgery: a pilonidal sinus.
AB  - Pilonidal sinus is an unglamorous surgical condition, often left to juniors, that
      is difficult to treat. Correct decisions in management may influence the
      prognosis of the condition by avoiding recurrence and continued sepsis.

PMID- 8287258
TI  - Multiple-choice questions: a guide to success.
AB  - Although many trainees have gained considerable experience in answering MCQs in
      undergraduate examinations, these papers are still a frequent cause of problems
      and failure for candidates of postgraduate examinations. This article aims to
      help trainees improve their technique so that their performance can more
      accurately reflect their knowledge and ability.

PMID- 8287259
TI  - Sudden respiratory distress in a child.

PMID- 8287261
TI  - The role of stress in the health and disease process.

PMID- 8287260
TI  - Fetal medicine: matters for concern.

PMID- 8287262
TI  - The cost of human interest.

PMID- 8287263
TI  - Effect of cooling the dentate nucleus of the cerebellum on hand movement of the
      monkey.
AB  - The functional role of the cerebellum in voluntary movement was investigated by
      local cooling of the cerebellar nuclei in three Japanese monkeys which performed
      hand movement tasks in response to visual stimuli. We implanted electrodes in
      various areas of the cerebral hemispheres to record field potentials in the
      cortex, and examined effects of the cooling upon the movement and field
      potentials. Cooling of the dentate nucleus ipsilateral to the moving hand
      reversibly increased the reaction time and reduced the size of surface-negative,
      depth-positive (s-N, d-P) field potential in the motor cortex contralateral to
      the hand. The potential preceded the movement by an almost constant time of about
      100 ms in the normal condition. The cooling remarkably prolonged and deviated the
      time. By shifting the cooling probe to different distances from the nucleus, we
      noted various decreases of the cooling effect. We also found a close correlation
      between the size of the s-N, d-P potential and the reaction time, i.e., when the
      potential was small, the reaction time was long. These findings support the
      following ideas; the motor command for this task comes to the motor cortex
      through the cerebello-thalamo-cortical pathway which includes the dentate
      nucleus, and produces the s-N, d-P potential as EPSP currents in pyramidal
      neurons in the motor cortex. We also studied self-paced movement task. In some
      cases, the cooling reduced the size of readiness potential in the motor cortex.

PMID- 8287264
TI  - Effect of the kappa-1 opioid agonist CI-977 on ischemic brain damage and cerebral
      blood flow after middle cerebral artery occlusion in the rat.
AB  - The effects of the kappa-1 opioid agonist CI-977 upon the volume of ischemic
      brain damage (defined using quantitative neuropathology) and local cerebral blood
      flow (CBF) (defined using quantitative [14C]iodoantipyrine autoradiography) have
      been examined at 4 h and 30 min, respectively, after permanent middle cerebral
      artery (MCA) occlusion in halothane-anesthetised rats. Treatment with CI-977 (0.3
      mg/kg, s.c.) 30 min before and 30 min after occlusion of the MCA reduced the
      volume of infarction in the cerebral hemisphere (reduced by 27% when compared to
      vehicle; P < 0.05) and cerebral cortex (reduced by 32%; P < 0.05), despite a
      marked and sustained hypotension, with only minimal effect on damage in the
      caudate nucleus. In the hemisphere contralateral to the occluded MCA, treatment
      with CI-977 (0.3 mg/kg, s.c.) 30 min prior to the induction of ischemia failed to
      demonstrate any significant effect on either the level of local CBF in any of the
      25 regions examined or on the volume of low CBF determined by frequency
      distribution analysis. In the hemisphere ipsilateral to MCA occlusion, CI-977
      failed to produce statistically significant alterations in either the level of
      local CBF in 23 of the 25 regions or on the volume of low CBF, but areas of
      hyperemia were observed in both the medial caudate nucleus and lateral thalamus
      (local CBF increased by 65% and 86%, respectively, when compared to
      vehicle).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287265
TI  - Modulation of thymidine incorporation by kappa-opioid ligands in rat spinal cord
      dorsal root ganglion co-cultures.
AB  - beta-Endorphin, met-enkephalin and several mu-selective opioid agonists were
      shown to decrease thymidine incorporation into DNA in various neural cell
      cultures. We now report that the kappa-selective opioid agonists U50488, U69593
      and MR2034 modulate [3H]thymidine incorporation into DNA in rat spinal cord
      dorsal root ganglion co-cultures. U50488 at 10 microM increased by 60% thymidine
      incorporation in 6-day-old cultures. The thymidine incorporation induced by
      U50488 was blocked by the kappa-selective antagonist nor-binaltorphimine, as well
      as by pertussis toxin and LiCl. U50488 treatment stimulated phosphatidylinositol
      turnover by three-fold compared with untreated controls. These findings suggest
      that kappa-opioid agonists modulate DNA synthesis in spinal cord-dorsal root
      ganglion co-cultures through a mechanism which involves pertussis toxin-sensitive
      GTP-binding proteins, as well as activation of phosphatidylinositol turnover.

PMID- 8287266
TI  - Long axon growth from embryonic neurons transplanted into myelinated tracts of
      the adult rat spinal cord.
AB  - Suspensions of embryonic mouse hippocampal neurons were micro-transplanted into
      the high cervical region of the corticospinal tracts and the ascending dorsal
      columns of immunosuppressed adult rat hosts. The mouse specific marker, M6,
      showed that the transplanted neurons grew long, straight, and uniform axons which
      passed both rostrally and caudally in a narrow beam within the tract occupied by
      the transplant. The donor axons did not fasciculate with each other, but were
      intermingled singly with the host myelinated axons, parallel to them and to the
      host interfascicular glial rows. The donor axons extended at about 0.5 mm per day
      for the first 6-10 days, after which they slowed down, gradually reaching a
      maximum distance of around 8 mm from the grafts by 6-7 weeks. Beyond this time M6
      ceased to be an effective marker. The presence of the donor axonal projections
      was confirmed by retrograde cellular labelling of the donor cells from injections
      of horseradish peroxidase caudal to the transplants in the same host tract. To
      test whether the donor embryonic hippocampal axons would be attracted to neuropil
      containing appropriate postsynaptic sites, embryonic rat hippocampal grafts were
      placed caudal to the mouse grafts. When placed where they could make direct
      contact with the projection, the rat grafts became M6 positive, suggesting that
      they had been innervated by mouse axons. But even when placed directly within the
      beam of donor projections, the rat grafts did not prevent large numbers of mouse
      axons from continuing caudally in the host spinal tracts. When the rat grafts
      were placed to one side of the beam of donor projection, the long projecting
      mouse axons did not deviate from their course. Thus the long ascending and
      descending myelinated fibre tracts of the adult spinal cord provide a permissive
      environment for the rapid growth of axons from embryonic donor neurons from a
      region not normally projecting to the spinal cord. The route taken by these axons
      is determined by the internal structure of the host tracts. Donor interfascicular
      axons are able to pass, without deviation, through or beside tissue containing
      appropriately matched postsynaptic targets.

PMID- 8287267
TI  - Identification of proton-translocating adenosine triphosphatases in rat cerebral
      microvessels.
AB  - To determine if proton translocating adenosine triphosphatases (ATPases) can be
      localized at the blood-brain barrier, isolated rat cerebral microvessels and
      cerebral synaptosomal preparations were assayed for ATPase activity in the
      presence of various inhibitors. N-ethylmaleimide-sensitivity could be
      consistently found in both cerebral microvessel and synaptosomal preparations.
      There was no vanadate sensitive component in the presence of ouabain, oligomycin
      and EGTA. Immunoblotting of cerebral microvessels and synaptosomes with a
      monoclonal antibody (E11) against the 31 kDa subunit of the vacuolar type H
      ATPase pump identified a discrete 31 kDa band. Diffuse immunocytochemical
      staining of cerebral cortical tissue, predominantly in choroid plexus, could be
      found with E11 but not with HK alpha N2, an H,K-ATPase specific antibody, nor
      with a non-specific mouse monoclonal antibody (MOPC-21). Immunoblotting with HK
      alpha N2 showed an immunoreactive 76 kDa band, not present with the preimmune
      serum or the antibody preabsorbed with the immunizing synthetic peptide. It is
      concluded that the vascular type H-ATPase and not the gastric H,K-ATPase is
      present in cerebral tissue including cerebral microvessels and choroid plexus.
      Non-specific immunoreactivity may account for the 76 kDa band observed in the
      immunoblots using the HK alpha N2 antibody although presence of a degradation
      product of H,K-ATPase can not be ruled out. The functional role of the vacuolar H
      ATPase in the blood-brain barrier remains to be determined.

PMID- 8287268
TI  - Aluminum decreases muscarinic, adrenergic, and metabotropic receptor-stimulated
      phosphoinositide hydrolysis in hippocampal and cortical slices from rat brain.
AB  - Effects of aluminum chloride (AlCl3) (0.1 to 1000 microM) on inositol phosphate
      (IP) accumulation stimulated by carbachol (CARB), norepinephrine (NE) or
      quisqualate (QUIS) were examined in rat hippocampal and cortical slices. In the
      absence of agonist, only 1000 microM AlCl3 significantly reduced basal
      accumulation of IPs. For CARB-stimulated IP accumulation, 100 microM and greater
      AlCl3 significantly inhibited IP accumulation. In cortical slices, 1000 microM
      AlCl3 reduced CARB-stimulated IP accumulation by 55% and in hippocampal slices
      1000 microM AlCl3 inhibited IP accumulation by 40%. Similar effects of AlCl3 were
      observed for NE-stimulated IP accumulation. In cortical slices, the concentration
      response for AlCl3 effects on agonist-stimulated IP accumulation was
      significantly different from that in hippocampal slices. For QUIS-stimulated
      accumulation of IPs, 1000 microM AlCl3 significantly inhibited IP accumulation in
      hippocampal slices. However, in cortical slices a biphasic effect of AlCl3 was
      observed. 500 and 1000 microM AlCl3 significantly inhibited IP accumulation,
      whereas 10 and 50 microM AlCl3 significantly enhanced QUIS-stimulated IP
      accumulation. In both hippocampal and cortical slices, 500 microM AlCl3
      significantly inhibited CARB-, NE- or QUIS-stimulated IP accumulation at all
      agonist concentrations (0.1 to 10000 microM) tested, indicating a post-receptor
      effect on agonist-mediated IP accumulation. Stimulation of G-proteins with NaF (5
      30 mM) resulted in accumulation of IPs in hippocampal and cortical slices in the
      absence of added agonists. NaF (5-30 mM) plus 1 mM CARB produced increased
      accumulation of IPs over CARB or NaF alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287269
TI  - Lateral olfactory tract input to dentate gyrus is depressed by prior
      noradrenergic activation using nucleus paragigantocellularis stimulation.
AB  - Nucleus paragigantocellularis stimulation potentiates the medial perforant path
      population spike in the dentate gyrus via beta-receptor activation. In this
      study, the same paragigantocellularis stimulation preceding lateral olfactory
      tract pulses depressed the lateral perforant path mediated synaptic potential in
      dentate gyrus. Depression of the lateral olfactory tract input was blocked by a
      beta-antagonist. These in vivo results confirm in vitro reports that
      norepinephrine induces potentiation of medial perforant path input and depression
      of lateral perforant path input to dentate gyrus.

PMID- 8287270
TI  - Inhibition of the soleus H-reflex in standing man.
AB  - There exists evidence to support the notion that the segmental reflex system is
      not fixed and inflexible, but rather is highly modifiable under a variety of
      circumstances. In this study the H-wave and M-wave recruitment curves were
      obtained from 19 subjects, utilizing the procedures outlined by Hugon. Each
      subject was tested on one day under two randomly administered conditions: (1)
      standing; and (2) prone. Once in place, the recording and stimulating electrodes
      were not removed until the completion of the study, to ensure that exact
      placement was maintained. A percutaneous electrical stimulus (1 ms pulse) was
      utilized to elicit the pulse. The current was monitored with a current probe, and
      was increased in 2 mA increments from zero until a maximal M-wave was obtained.
      An analysis of variance revealed significant increases in the amplitude of the H
      wave (P < 0.05) when the subject was prone with no significant increases in the M
      wave. The results indicate significantly higher H/M ratios with the subjects in
      the prone position. Therefore, it is concluded that H-reflex amplitude is
      tonically depressed when the subject is maintaining a standing position.

PMID- 8287271
TI  - Exposure to sub-lethal ischemia failed to prevent subsequent ischemic death of
      dentate hilar neurons, as estimated by laminin immunohistochemistry.
AB  - The CA1 pyramidal cells and dentate hilar neurons are selectively vulnerable to
      forebrain ischemia. Although brief ischemia induces tolerance to subsequent
      ischemia in the CA1 pyramidal neurons, a protective effect of preceding brief
      ischemia on the dentate hilar neurons has not been established. We observed that
      vulnerable dentate hilar neurons were strongly laminin-immunopositive and used
      laminin immunohistochemistry to estimate the fate of dentate hilar neurons after
      ischemia. Pretreatment of brief sublethal ischemia, which effectively protects
      the CA1 neurons, failed to prevent the death of dentate hilar neurons. These
      results indicate that brief ischemia failed to induce tolerance to subsequent
      longer ischemia in the dentate hilar neurons.

PMID- 8287272
TI  - Facilitation of cocaine kindling by glucocorticoids in rats.
AB  - We report that glucocorticoids significantly facilitated the development of
      cocaine-induced kindled seizures. These results suggest that glucocorticoids may
      have effects on the development of kindled seizures which are similar to those of
      the neuropeptide, corticotropin-releasing hormone (CRH), with which they show a
      close functional relationship. These results may be of interest in the light of
      data showing that glucocorticoids increase CRH expression in the central nucleus
      of the amygdala, which is an important site for the development of kindling.

PMID- 8287273
TI  - Decrease of hippocampal choline acetyltransferase activity induced by formalin
      pain.
AB  - The involvement of the hippocampal choline acetyltransferase (ChAT) activity in
      the response to tonic pain was investigated in rats injected with formalin,
      either 50 microliters 10% or 50 microliters 0.1%. Hippocampal ChAT activity was
      found to be reduced both 30 and 60 min after injection of the higher
      concentration of formalin but only 30 min after the lower one. Results indicate
      that the decrease in ChAT activity depends upon the presence of the nociceptive
      input rather than its magnitude. The hippocampal formation is involved in the
      specific behavioural response to pain, namely licking.

PMID- 8287274
TI  - Liposome targeting to rat brain: effect of osmotic opening of the blood-brain
      barrier.
AB  - To determine whether sulfatide liposomes can cross the blood-brain barrier (BBB)
      with or without osmotic treatment by mannitol, we administered liposomes through
      the internal carotid artery in rats. Sulfatide liposomes could pass the BBB with
      osmotic treatment, but not without osmotic treatment. Therefore, we propose that
      the combination method of administration of the reticuloendothelial-system
      avoiding liposomes with osmotic treatment can be useful for treatment of various
      kinds of brain diseases.

PMID- 8287275
TI  - Microinjections of the metabotropic glutamate receptor agonist, trans-(+/-)-1
      amino-cyclopentane-1,3-dicarboxylate (trans-ACPD) into the amygdala increase the
      acoustic startle response of rats.
AB  - The present study examined the effect of intraamygdaloid application of the
      metabotropic glutamate receptor agonist trans-ACPD on the acoustic startle
      response. Trans-ACPD led to a disruption of between-session habituation which is
      normally seen after repeated testing after injections of the vehicle into the
      amygdala. More specifically, a statistically significant increase of the
      magnitude of the startle response was observed 4 h after injection of 30 nmol of
      trans-ACPD into the central amygdaloid nucleus. The present findings suggest a
      role for the metabotropic glutamate receptor in the amygdala in the enhancement
      of the acoustic startle response.

PMID- 8287276
TI  - Independence of steady-state 40-Hz response and spontaneous 10-Hz activity in the
      human auditory cortex.
AB  - We recorded neuromagnetic signals from 5 subjects with a 24-channel planar SQUID
      gradiometer. Our aim was to search for any relationship between the 40-Hz steady
      state responses and the spontaneous 10-Hz activity in the auditory cortex. Source
      strengths and locations of spontaneous activity were determined from spectral
      components of the data, and sources within the auditory cortex were determined by
      restricting the source location to a neighborhood of the auditory evoked response
      to single clicks. The characteristics of the 40-Hz steady-state responses were
      not simply related to those of the spontaneous 10-Hz activity, even within
      subjects, suggesting that these two oscillatory phenomena have independent
      generators.

PMID- 8287277
TI  - Ipsilateral corticotectal pathway inhibits the formation of long-term
      potentiation (LTP) in the rat superior colliculus through GABAergic mechanism.
AB  - The purpose of the present experiments was to clarify the possible mechanism for
      the depression of long term potentiation (LTP) induction in the superficial gray
      layer of the rat superior colliculus after optic nerve stimulation. A
      postsynaptic field potential was recorded in vitro in the superficial gray layer
      of superior colliculus slices after stimulation of the optic layer. Tetanic optic
      layer stimulation (50 Hz, 20 s) induced LTP of the postsynaptic field potential
      elicited in the superficial gray layer. The postsynaptic field potential, with
      unitary discharges, produced in the superficial gray layer by optic nerve
      stimulation in vivo was depressed by a conditioning stimulus to the visual
      cortex. Identical inhibition of the cortical response of the superficial gray
      layer was produced by optic nerve stimulation. The application of picrotoxin (2.5
      mg/kg, i.p.), a GABAA antagonist or methoxypyridoxine (100 mg/kg, i.v.), an anti
      glutamate decarboxylase agent which reduces GABA levels, blocked the inhibitory
      interaction between the optic nerve-superficial gray layer and visual cortex
      superficial gray layer. Tetanic optic nerve stimulation (50 Hz, 20 s) failed to
      induce LTP in the superficial gray layer of the intact rat. LTP was only elicited
      by tetanic optic nerve stimulation when picrotoxin or methoxypyridoxine was
      administered prior to the tetanic stimulation and when the ipsilateral visual
      cortex was removed. These results indicate that GABAergic interneurons in the
      superficial gray layer activated by corticotectal input, may stop the formation
      of LTP in the superficial gray layer.

PMID- 8287278
TI  - Conditioned increases in mesolimbic dopamine overflow by stimuli associated with
      cocaine.
AB  - Stimuli associated with cocaine come to acquire incentive-motivational as well as
      secondary reinforcing properties which can energize and maintain behavior in
      laboratory animals as well as precipitate craving in addicts. Environmental
      stimuli paired with a large dose of cocaine for one training session elicited
      significant increases in locomotor activity and in extracellular dopamine in the
      nucleus accumbens of rats during a second test session with a low dose of
      cocaine. The increases in extracellular dopamine are not likely a secondary
      consequence of this increase in locomotor output of rats conditioned to cocaine,
      since doses of MK-801 which produced similar increases in locomotor behavior had
      no effect on mesolimbic dopamine. These findings provide a neurochemical
      mechanism for understanding the incentive motivational properties of stimuli
      associated with cocaine and may help to explain recidivism of cocaine addicts
      when they return to an environment in which the drug was used.

PMID- 8287279
TI  - The extent of phosphorylation of fetal tau is comparable to that of PHF-tau from
      Alzheimer paired helical filaments.
AB  - The relationship between Alzheimer's disease (AD) and expression of fetal
      proteins was examined by: (i) determining the phosphate content of tau prepared
      from fetal brains (F-tau); (ii) comparing F-tau, tau from normal adult human
      brains (N-tau) and tau from paired helical filaments in AD brains (PHF-tau) for
      phosphate content; and (iii) testing the reactivity of F-tau with five antibodies
      known to recognize PHF-tau. The antibodies have been reported to recognize
      phosphate dependent epitopes at the carboxy-terminal half of the tau molecule.
      Our data shows that on the average, F-tau contains 7 mol phosphate/mol protein,
      which is comparable to the phosphate content of PHF-tau, but is 3-4 times higher
      than that of N-tau. Immunoblotting shows that all of the tested antibodies
      reacted with F-tau on immunoblots, indicating that F-tau and PHF-tau are
      phosphorylated at similar sites. A difference between PHF-tau and F-tau is the
      state of phosphorylation in the Tau-1 epitope, an epitope reactive with a
      monoclonal anti-tau antibody, Tau-1. This epitope, which is phosphorylated in all
      PHF-tau, is phosphorylated only in some of the F-tau. The sharing of
      phosphorylated sites between F-tau and PHF-tau has also been reported by others
      in studies with antibodies to different and similar phosphorylated epitopes.
      Together these observations indicate that the extent and the site of
      phosphorylation in F-tau and PHF-tau tau are similar.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8287280
TI  - Amyloid beta-protein stimulates casein kinase I and casein kinase II activities.
AB  - Amyloid beta-protein (A beta) is the major protein of cerebrovascular and plaque
      amyloid in Alzheimer's disease (AD). Extensive evidence has demonstrated abnormal
      protein phosphorylation in this disease. We investigated the effect of synthetic
      A beta with the amino-acid sequence corresponding to cerebrovascular A beta and
      plaque A beta on the activities of casein kinase I (CK I) and casein kinase II
      (CK II). These enzymes were purified from bovine brain and casein was used as a
      substrate. A beta was found to stimulate markedly CK I- and CK II-mediated
      phosphorylation of casein in a concentration-dependent manner. The effect of
      plaque A beta was considerably higher than that of cerebrovascular A beta.
      Heparin, which is known to be a specific inhibitor of CK II, completely inhibited
      A beta-stimulated CK II activity. A beta itself was not a substrate for casein
      kinases. These findings were confirmed using other substrates for CK I and CK II.
      The experiments with synthetic CK II-substrate peptide (Leu-Glu-Leu-Ser-Asp-Asp
      Asp-Asp-Glu) and the phosphorylation of erythrocyte membrane proteins by
      intrinsic membrane-bound CK I in erythrocytes showed marked stimulation in
      activities of casein kinases in the presence of A beta 1-40 or blocked A beta. We
      propose that A beta, by stimulating casein kinases, may contribute to abnormal
      protein phosphorylation in AD, in particular to increased phosphorylation of
      microtubule-associated proteins, leading to the neurofibrillary tangles formation
      and neurodegeneration in this disease. Interaction of A beta with protein
      kinases, thus, may characterize the beginning of the disease.

PMID- 8287281
TI  - Characterization of slow postsynaptic K+ current of Aplysia LUQ neurons in
      culture.
AB  - We have characterized the slow inhibitory synaptic connection between an left
      upper quadrant (LUQ) neuron and neuron L10, L12 or L13 in culture. A slow
      postsynaptic outward current in the LUQ neuron was elicited by repetitive firing
      of the co-cultured cholinergic neuron L10 as well as neuron L12 or L13 which were
      not cholinergic but FMRFamide synthesizing neurons. This outward current was due
      to an increase in K+ conductance and was relatively insensitive to external
      application of tetraethylammonium and 4-aminopyridine. We also investigated the
      effects of injection of a guanosine 5'-triphosphate (GTP) analogue into the LUQ
      neuron and extracellular application of serotonin and an adenosine 3',5'-cyclic
      monophosphate (cAMP) analogue on the current. In all the investigated properties,
      no significant difference was found among neuron L10, L12 and L13 as a
      presynaptic neuron. The slow postsynaptic current appeared to be virtually
      identical to the FMRFamide or acetylcholine (ACh)-induced K+ current reported in
      vivo, which resembled the 'S' current in Aplysia sensory neurons. We performed
      experiments to see the effect of phenyltrimethylammonium, an ACh antagonist, on
      the postsynaptic, ACh-, and FMRFamide-induced currents, clearly indicating that
      the neurotransmitter used in the cultured synapses was not ACh.

PMID- 8287282
TI  - Expression of c-Fos-like immunoreactivity in the caudal medulla and upper
      cervical spinal cord following stimulation of the superior sagittal sinus in the
      cat.
AB  - Migraine is an episodic vascular headache with a well-recognized clinical picture
      but a poorly understood pathogenesis. Stimulation of a pain-sensitive
      trigeminally innervated intracranial structure, the superior sagittal sinus
      (SSS), was undertaken to map the higher-order neurons potentially involved in the
      processing of vascular head pain. The animals were prepared for stimulation by
      exposure of the sinus and then maintained under alpha-chloralose anaesthesia for
      24 h before SSS stimulation, perfusion and immunohistochemical processing for the
      detection of Fos protein. Examination of the medulla and upper cervical cord
      revealed marked increases in Fos-like immunoreactivity in laminae I and IIo of
      the trigeminal nucleus caudalis and the dorsal horn of the upper cervical spinal
      cord. In addition, Fos-like immunoreactivity was observed in lamina X of the
      upper cervical spinal cord, in the commissural and medial nuclei of the solitary
      tract and in the nucleus retroambigualis. The use of immunohistochemical
      detection of Fos has allowed visualization of several populations of neurons
      likely to be involved in the central neural processing of vascular headache
      syndromes, particularly migraine.

PMID- 8287283
TI  - Damage control.

PMID- 8287284
TI  - A legacy of violence in nonorganic failure to thrive.
AB  - It is often postulated that a mother's past experiences influence her ability to
      function as a parent. If those past experiences involve her as a victim of abuse,
      what lies ahead for her offspring? We studied 59 mothers of children referred for
      nonorganic failure to thrive (NOFTT) to the University of Colorado Health
      Sciences Center and compared their abuse history with a group of 131 mothers of
      children with normal growth. The mothers of NOFTT children were younger but of
      the same socioeconomic groups as the comparison mothers. Mothers of NOFTT
      children had a significantly higher history of abuse when compared to the
      comparison group p < 0.001. A surprising 80% of mothers of NOFTT children
      reported they were victims of abuse. We alert clinicians to the likelihood that
      mothers of children with NOFTT may be victims of abuse and that successful
      treatment of the child depends upon treatment of the mother-child dyad.

PMID- 8287285
TI  - The Psychological Maltreatment Rating Scales.
AB  - Psychological maltreatment is gaining recognition as one of the core concepts in
      child welfare, however, its utility has been limited by definitional problems and
      the absence of operationalized and validated instruments. These Psychological
      Maltreatment Rating Scales (PMRS) were developed for assessing psychological
      maltreatment in mother-child interaction, and were used to rate the videotaped
      interaction of 49 high-risk mother-child dyads and make predictions of child
      protective service involvement with the dyads. These predictions are compared
      with predictions based upon mothers' personal resources and social support.
      Results show that the PMRS is a moderately reliable and valid measure of
      psychologically maltreating and prosocial parental behavior that can discriminate
      between maltreating and comparison parents, and is a more effective predictor
      than maternal measures. Three factors of parenting emerged from an exploratory
      factor analysis: emotional abuse, and two factors of positive parenting.
      Psychological abuse was the presence of hostile behavior, and psychological
      neglect the absence of positive parenting.

PMID- 8287286
TI  - Development, reliability, and validity of a child dissociation scale.
AB  - Dissociation is a complex psychophysiological process that ranges along a
      continuum from minor, normal dissociation to Axis I psychopathology. High levels
      of dissociation are associated with increased self-destructive behaviors and
      other symptoms. Although several validated measures of dissociation exist for
      adults, no measures are available for children. The Child Dissociative Checklist
      (CDC) was developed to meet this need and is a reliable and valid observer report
      measure of dissociation in children. The CDC had a 1-year test-retest reliability
      coefficient of rho = .69 (N = 73, p = .0001) in a sample of normal and sexually
      abused girls. The CDC had high discriminant validity among four test samples
      including: normal control girls, sexually abused girls, boys and girls with
      dissociative disorder NOS and boys and girls with multiple personality disorder.
      The CDC is intended as a clinical screening instrument and as a research measure.
      The CDC is not designed to be used as a diagnostic instrument.

PMID- 8287287
TI  - A follow-up study of behavior problems associated with child sexual abuse.
AB  - The objectives of this study were to examine: (a) behavior in children evaluated
      for sexual abuse, (b) the stability of their behavior over 4 months, and (c) the
      relationship between aspects of the abuse and the children's behavior. The Child
      Behavior Checklist (CBCL) was completed by parents of 93 prepubertal children
      evaluated for sexual abuse and 80 nonabused children matched on age, gender, and
      race. A follow-up CBCL was completed after 4 months by 45% of parents of abused
      children. Sexually abused children had significantly more behavior problems than
      comparison children, including depression, aggression, sleep and somatic
      complaints, hyperactivity, and sexual problems. At follow-up, only those children
      who initially had externalizing behavior in the clinical range improved
      significantly. During the initial evaluation, behavior problems were associated
      with the child's disclosure of abuse and during follow-up, behavior problems were
      associated with abnormal physical findings. However, behavior problems were not
      related to characteristics of the abuse or perpetrator, likelihood of abuse, or
      therapeutic services. The persistence of behavior problems suggests that children
      suspected of having been sexually abused should receive an assessment of their
      psychological status and careful follow-up.

PMID- 8287288
TI  - The impact of maternal history and behavior upon foster placement and adjustment
      in sexually abused girls.
AB  - This study investigated the impact of the nonoffending mother's childhood history
      and current functioning upon the psychological status and placement decisions for
      68 sexually abused girls. Maternal history of abuse and/or poor childhood
      attachment relationships were significantly related to current maternal substance
      abuse. Maternal substance abuse and dissatisfaction with social support were
      significantly associated with lack of maternal support to the child and more
      abuse incidents, which in turn were related to more sexual abuse-related
      symptomatology and placement in foster care. The findings are congruent with
      studies indicating that intergenerational transmission of abuse is not
      inevitable, and suggest that maternal substance abuse and social isolation are
      important mediating variables between maternal history of sexual abuse and
      response to the abused child. The findings suggest that interventions targeted to
      the nonoffending mothers may be important in reducing child dysfunction and
      placement in foster care in the aftermath of sexual abuse.

PMID- 8287289
TI  - An analysis of allegations of sexual abuse in a multi-victim day-care center
      case.
AB  - Sexual abuse in day-care centers is a phenomenon of increasing concern, both in
      terms of its prevalence and its serious effects on child victims. Legal
      intervention in this area is problematic because criminal investigations are
      usually beset with difficulties: Characteristics of children and of the abuse
      situation affect disclosure rates and credibility. Research on children as
      witnesses is amassing; however, so far, little systematic analysis has been
      conducted on multi-victim child sexual abuse cases. The present study concerns a
      case of sexual abuse in a day-care center with over 100 alleged victims. Criteria
      derived from Statement Validity Analysis (SVA) protocols were applied to
      aggregate record review data to assess the veritability of the abuse allegations.
      Individual children's abuse disclosures were also analyzed, vis-a-vis
      characteristics of the children (age, gender, recency of attendance) and of the
      investigation (agency doing the interview, number of interviews, use of
      anatomically detailed dolls). The use of SVA criteria supported the veritability
      of allegations in this day-care abuse case. Even acknowledging the limitations of
      archival data collected for other purposes, the aggregate data analysis reflected
      consistency, logical structure, and spontaneity; however, little evidence of
      accommodation was found. Multivariate comparison of disclosing and nondisclosing
      children found an unexpected inverse relationship of disclosure with age, as well
      as positive associations with number of interviews and use of dolls. Alternative
      interpretations of these results are discussed.

PMID- 8287290
TI  - Challenges we face in understanding children and war: a personal essay.
AB  - War is a correlate of child abuse in several respects. War generally elevates the
      level of violence in the warring society, and thus increases risk for abuse. War
      disrupts communities and families (and thereby presumably undermines social
      support systems and increases single parenthood). War kills and maims children
      and their caregivers; it is abuse. This article presents an analysis of
      psychological and cultural issues faced by professionals dealing with children
      exposed to war zones. The premise for this article lies in the recognition that
      "war" is so powerfully loaded on subjective and ideological meanings for all
      adults (including professionals) that self-reflection and cultural criticism is a
      necessary condition for going forward effectively with children.

PMID- 8287291
TI  - The effects of chronic violence on preschool children living in South African
      townships.
AB  - Violence in South Africa has reached endemic proportions. To date, more than
      11,000 people have died in politically related violence. The present study is
      specifically concerned with researching the psychological sequelae of civil
      conflict and violence on preschool children. Using a combination of participatory
      and empirical methods, five creche teachers (also trained as field workers) took
      a random sample of 148 children in their creches. The Post Traumatic Stress
      Disorder Questionnaire for Children was completed by the creche teachers for each
      of the children under their care. Second, the children were asked to draw
      pictures of things they had experienced in their life. A significant finding of
      this study was that preschool children exposed to violence suffered from PTSD.
      Further, children's drawings showed severe emotional indicators. However, an
      interesting finding was that these drawings were not good predictors of PTSD; the
      more a child was able to express emotional trauma through drawings, the less
      likely he/she would suffer from PTSD. This finding has interesting ramifications
      for trauma intervention programs for preschool children.

PMID- 8287292
TI  - Ecological integrated model of children of war: individual and social psychology.
AB  - The psychological trauma associated with war is a topic that has occupied the
      attention of mental health researchers and practitioners for some time. Most of
      their attention, though, has focused on the traumatic stress of soldiers, and
      little attention has been paid to the problems and traumatization of civilians
      caught in war zones, especially the children. In this paper, the limited research
      on children of war is reviewed, and themes are extracted. Children suffer from
      both acute and chronic traumatic stress. The key to determining the amount of
      suffering has to do with the dynamic interaction among five processes within an
      ecological framework: the child's psychobiological makeup, the disruption of the
      family unit, the breakdown of community, and the ameliorating effects of culture.
      The intensity, suddenness and duration of the war-like experience itself
      constitute an additional component to this ecological model. In the final
      section, psychotherapeutic guidelines to help children cope with symptoms
      associated with war are presented for current and future caregivers. The
      prevention of war should be the primary task of all.

PMID- 8287293
TI  - Children living through a Desert Storm.
AB  - Mental health professionals have long been concerned about how children react to
      war. This paper reports a small, naturalistic study of how children reacted to
      Operation Desert Storm. Although no actual danger threatened these affluent east
      coast children, television transported the battle zone's gory pictures right into
      the living room. That experience had a deep impact on many children. Not only did
      they empathize with the wounded and maimed; they also resented the way injured
      people's privacy was invaded and were bewildered by news reporters' "bizarre"
      behavior when danger was imminent.

PMID- 8287294
TI  - Who are "street children?" A hierarchy of street use and appropriate responses.
AB  - "Street children" have come to public attention again as they did in the guise of
      the "street Arabs," "blackguards," and "war-vagrants" at periods of European
      history. Is this classification useful when considering education/welfare policy,
      or does it artificially mark a group for special attention in a manner that is
      misleading? There are two perspectives: (a) that this classification is
      imperfect, which leads to incorrect intervention; or (b) that unclassified can
      mean unrecognized and that labels are a prerequisite of motivating a response.
      From a comparative analysis, this paper proposes a working compromise based on a
      hierarchy of street use, from minimal to total dependency on the streets. Four
      overlapping levels are discussed: (a) beneficial street use; (b) an "assumed
      adult" status; (c) those who suffer school exclusion; and (d) a state of
      "degenerative estrangement." The aim of the hierarchy is to demonstrate the need
      for different types of education/welfare intervention at different levels.
      Intervention needs to emphasize three types of change: (a) in awareness of street
      life for those making little use of the streets; (b) in the capabilities of those
      using the street as a major resource; and (c) of the condition of those totally
      dependent on the street environment.

PMID- 8287296
TI  - [Considerations apropos of failures in the treatment of chronic pain].

PMID- 8287295
TI  - Psychological well-being of refugee children.
AB  - Two groups of refugee families participated in a program aimed at preventing
      children's mental health problems. The program attempted to gain insight into the
      character and scope of problems of refugee families and to develop and implement
      a spectrum of interventions that would meet their specific psychological needs.
      Data about the family situation and the psychosocial adaptation of refugee
      children to displacement was gathered during detailed structured interviews with
      the mothers, while the study families were accommodated either in a shelter or
      with host families. A considerable range of stress-related reactions among
      displaced children were identified (e.g., sleeping and eating disorders,
      separation fears, and withdrawal or aggression). Refugee children exhibited a
      significantly higher incidence of stress reactions if their mothers had
      difficulty coping with the stress of displacement. The findings also indicated
      that children in the collective shelter were at greater mental health risk than
      their peers housed with host families.

PMID- 8287297
TI  - [The sympathetic system and chronic pain in pediatrics].
AB  - Sympathetic dystrophy is defined as continuous pain in a portion of an extremity
      after trauma not involving a major nerve. It may be exacerbated by movement,
      physiotherapy or stress. There are sympathetically mediated changes with initial
      vasodilatation and if untreated progress to a second dystrophic stage. In 2 years
      48 patients (7-17 years) were evaluated and treated by the same protocol. For the
      majority of cases the time from the start of pain until the time of treatment was
      less than 60 days. The treatment was always performed by technical procedures:
      i.v. regional guanethidine, long-term epidural catheter or lumbar sympathetic
      blocks. In case of chronic pain the role of sympathic nervous system must be
      debatable and it is absolutely necessary to perform a treatment such as it is not
      a simple technic but always a safe technic.

PMID- 8287298
TI  - [Postdural puncture headache].
AB  - PDPH are not the privilege of spinal anaesthesia, as they can occur in various
      circumstances including epidural anesthesia, surgical wound of the dura, spinal
      tap and/or myclography. Diagnosis PDPH can be discussed with four etiologies:
      cortical vein thrombosis, meningitis, intracranial haematomas (intracerebral,
      subdural) or migraine. PDPH result from the leakage of CSF via the dural hole,
      responsible of hypotension of CSF in the subarachnoid compartment. Several
      etiologies and predisposing factors are discussed. The incidence of PDPH varies
      with age, maximum from 15 to 50 years-old, the decreasing to reach a very low
      incidence over 65 PDPH seems to occur more frequently in women, especially during
      pregnancy. The diameter of the spinal needle is the main factor of PDPH. Using
      small diameters (25 G and less) allows to reduce the percentage of PDPH, as well
      as using specially designed needles with a "pinpoint bevel" (Spritte, Whitacre).
      When PDPH occur, no specific treatment is required before the fifth day, as they
      spontaneously resolve in 80% of the patients, without any intervention. After
      then, epidural blood patch allows 90% success rate. Other therapeutic proposals
      are discussed. Finally, prevention of PDPH appears to be the keypoint, paying
      particular attention to the choice of the needle and of the spinal puncture
      technique.

PMID- 8287300
TI  - [The use of patient-controlled analgesia by the obstetrical patient].
AB  - Patient-controlled analgesia is a technique of analgesia recently developed for
      obstetrical pain. During labor, PCA using intravenous administration has already
      been used for more than a decade but meperidine may be conceivable replaced by
      fentanyl with which maternal and neonatal side-effect seem reduced. This
      analgesic technique is however less efficacious than epidural analgesia and thus
      might essentially be useful in situations when the latter is contra-indicated.
      During labor, patient-controlled epidural analgesia (PCEA) may produce powerful
      pain relief and may reduce local anesthetic doses thus reducing motor blockade.
      After cesarean section, PCA using intravenous morphine has been shown to produce
      less pain relief than epidural morphine but is associated with a high degree of
      satisfaction. The wider use of PCA in obstetrics is however limited by its cost
      and will thus require evaluation of its cost/effectiveness ratio.

PMID- 8287299
TI  - [Cardiotoxicity of local anesthetics].
AB  - The intravascular administration and the high blood resorption of local
      anesthetic agents are known to induce neurotoxic accidents. However, the use of
      potent local anesthetic drugs such as bupivacaine is responsible for serious
      cardiotoxic accidents with a mortality of about 50%. Indeed, bupivacaine induces
      both electrophysiologic and haemodynamic disturbances with the occurrence of
      conduction blocks, arrhythmias and cardiovascular collapse. Moreover,
      cardiotoxicity is worsened by: bupivacaine-induced sympathetic activation which
      facilitates tachycardia and arrhythmias, metabolic abnormalities such as hypoxia,
      acidosis, hyperkaliemia and hypothermia, pregnancy, diazepam pretreatment, and
      the antiarrhythmic drugs. In case of cardiac arrest, CPR must be made. In the
      other cases, the first treatment is to oxygenate, to intubate the trachea and to
      ventilate the lungs, and then to stop convulsions. Specific cardiac resuscitation
      remains controversial because it is based principally on experimental results. We
      demonstrated that the combination of clonidine and dobutamine is efficient to
      reverse both haemodynamic and electrophysiologic impairments induced by a large
      dose of bupivacaine in anesthetized dogs. Whatever the efficiency of specific
      resuscitation, it must be emphasized that prevention of toxic accident must
      always include: the best choice of local anesthetic drug (e.g.: lidocaine+alpha-2
      agonist vs bupivacaine), test dose, aspiration and slow administration. Finally,
      the monitoring of regional anaesthesia must be similar to that in use for general
      anaesthesia and drugs and devices for resuscitation must be ready.

PMID- 8287301
TI  - [Prevention and treatment of hypotension during spinal anesthesia].
AB  - Spinal and epidural anaesthesias alter self-regulation of arterial pressure as
      they lead to a sympathetic blockade. The extent and the speed of appearance of
      this blockade conditions the magnitude of the decrease of arterial pressure. So,
      epidural or spinal anaesthesias may only be performed on hemodynamically stable
      patients for a non hemorrhagic surgery. The routine fluid preloading is illogical
      and poorly efficient. Correcting a deep arterial hypotension demands first of all
      the use of vasoconstricting agents the choice of which depends on the site of the
      anaesthesia and on the cardiovascular condition of the patient. The occurrence of
      bradycardia more often indicates a hypovolaemic state.

PMID- 8287302
TI  - [The real risks of locoregional anesthesia].
AB  - Regional anaesthesia involves its own risks of which five main categories appear
      to stand out: 1. Excessive indications, especially of epidural anaesthesia
      instead of nerve blocks or general anaesthesia. 2. Delayed use of vasopressive
      amines after excessive fluid infusion. 3. Toxicity of local drugs which can be
      largely avoided by slow injection. 4. Neurological complications of traumatic
      punctures, such as nerve root or dura mater injury. 5. Excessive complementary
      sedation.

PMID- 8287303
TI  - [The clinical reality of preventive analgesia].
AB  - Preemptive analgesia is based on neurophysiological studies suggesting that a
      nociceptive input may induce a prolonged hyperexcitability of the central nervous
      system. This plasticity of the nervous system seems to be more easily prevented
      than treated. The clinical application of preemptive analgesia is not yet
      possible. Further clinical and fundamental studies using a good methodology are
      necessary. This article reviews available clinical data with a special interest
      for anti-inflammatory drugs that the author has personally evaluated.

PMID- 8287304
TI  - Cancer pain management.
AB  - Cancer pain can be relieved with oral analgesics in most cases but 10 to 20% of
      patients do not respond. They are presently called opioid-resistant. While mild
      pain can be treated by paracetamol and non steroidal anti-inflammatory drugs,
      strong opioids are needed frequently. The author believes that there is no place
      for the weak opioids in cancer pain treatment. With strong opioids side effects
      are frequent, whether given orally (as is to be tried whenever possible),
      rectally or by other routes. Epidural or spinal delivery needs a special support
      system. Associations with steroids, antidepressants or other drugs are
      recommended. Nerve blocks and neurolytic procedures and methods such as
      transcutaneous nerve stimulation and acupuncture can be helpful.

PMID- 8287305
TI  - [The use of locoregional anesthesia in the prevention of postoperative pain].
AB  - Preemptive analgesia is a new concept suggesting that postoperative pain may be
      attenuated if the transmission of pain is blocked before the occurrence of
      noxious stimuli. The widespread use of regional anesthesia whether or not
      associated to general anesthesia has contributed to the improvement of
      postoperative pain both in ambulatory surgery and inpatients. Numerous studies
      have demonstrated that postoperative analgesia was better after regional
      anesthesia when compared to general anesthesia. However, preemptive analgesia
      means the benefits of an analgesia technique administered before (no after) the
      occurrence of noxious stimuli. Unfortunately, very few studies have met this
      principal criteria in their design. Moreover, other criterias are also important
      in investigating preemptive postoperative analgesia such as: 1) the duration of
      preemptive analgesia (catheter,...); 2) the importance of surgical stress; 3) the
      multiple components of postoperative pain; 4) the analgesics used; 5) the route
      of administration. In conclusion, the participation of regional anesthesia in
      preventing postoperative pain remains controversial. Numerous studies are needed
      in the future. These studies should take into account the above criterias and
      should include a large number of patients in order to find first the type of
      surgery that could benefit and second, the preemptive analgesia treatment that
      should be used in such indications.

PMID- 8287306
TI  - [The 3-in-one block].

PMID- 8287308
TI  - [Digital local anesthesia through the flexor sheath].

PMID- 8287307
TI  - [Lower limb blocks in children].
AB  - Conduction blocks have important advantage over spinal blocks for unilateral low
      extremity surgery in children. The complexity of innervation compared with upper
      limb is more apparent than real and a good understanding of fascial diffusion
      spaces is as essential as it is of neural pathways. Useful techniques can be
      classified into two groups, proximal blocks and distal blocks. Beside emergency
      situations, proximal blocks are usually performed under light general
      anaesthesia, with the aid of a neurostimulation. The most used proximal blocks
      are the femoral block, the sciatic nerve block and to a lesser degree the lumbar
      plexus direct blockade. Distal blocks can complete a non quite satisfactory
      proximal block, or be effected so as to obtain analgesia in a limited area (in a
      cooperative vigil patient). Some of these consist of several anaesthetic
      subcutaneous infiltrations for which no costly material nor special dexterity are
      required. A judicious choice among the main available techniques allows an
      excellent analgesia with a very low cost and almost no risks.

PMID- 8287309
TI  - [Lumbosacral plexus block by the paravertebral route].
AB  - The authors present a detailed account of a technique of peripheric anesthesia of
      the lower limb, obtained with a single transcutaneous injection, blocking lumbar
      and sacral plexus, by a paravertebral way. Encouraging results have been reached
      in the treatment of both old (no cerebral or cardiorespiratory depressant
      effects) and young patients, which are frequently under day-hospital treatment.
      According to their experience, this technique is simple, easy to perform and less
      dangerous if compared to anesthesia obtained by spinal approach.

PMID- 8287310
TI  - [The truncal blocks of the foot].
AB  - Among the five branches of principal nerves trunks supplying the ankle and foot,
      only the tibial nerve is sometimes difficult to block at the ankle, at the border
      of the medial malleolus. Using new landmarks at the level of the sustentaculum
      tali overcomes this problem. Blocking these five nerves make possible all
      surgical procedures on the foot and provide excellent postoperative analgesia.
      Only tourniquet is a limit for these blocks.

PMID- 8287312
TI  - [Spinal anesthesia: a new technique of access to the intrathecal space].

PMID- 8287311
TI  - [Truncal and peripheral blocks of the arm].
AB  - Blocking the median, the radial, the ulnar and the musculo-cutaneous nerves,
      alone or all together provide sufficient anaesthesia for hand and forearm
      surgery. Because of frequent anatomical variations and the possibility of a
      double nerve supply in some territories, blockade must be extended to the
      adjacent nerves. Tourniquet over the elbow is the only limit for these blocks,
      but they are useful to provide per and postoperative analgesia during general
      anaesthesia, and in some cases to improve the efficiency of brachial plexus
      block.

PMID- 8287313
TI  - Cytokines and bone metabolism.

PMID- 8287314
TI  - Pharmacokinetic evaluation of pamidronate after oral administration: a study on
      dose proportionality, absolute bioavailability, and effect of repeated
      administration.
AB  - To evaluate dose proportionality and absolute bioavailability of a new enteric
      coated pellet formulation of pamidronate disodium (AREDIA), nine females (aged 52
      66 years) were given three different single peroral doses of pamidronate disodium
      (75, 150, and 300 mg) and an i.v. infusion of 15 mg over 30 minutes at constant
      infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12
      females (aged 51-70 years) for 10 consecutive days. Urinary excretion of
      pamidronate after peroral and i.v. administration was used for estimation of
      pamidronate absorption. Renal excretion of pamidronate ranged from 0.01% to 0.35%
      of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg,
      respectively. After i.v. infusion, the renal excretion of pamidronate was 26-53%
      of the dose, lower than for other bisphosphonates. The absolute bioavailability
      was 0.31% (range 0.08-0.7%) after 75 mg, 0.43% (0.01-1.20%) after the 150-mg
      dose, and 0.48% (0.07-1.06%) following 300 mg of pamidronate disodium. Urinary
      excretion after the 10th intake showed a significant increase (difference 0.07%
      (range -0.003-0.29%), P < 0.02) when compared with the first dose. In conclusion,
      intestinal uptake of pamidronate was low with high intraindividual variation,
      like other bisphosphonates.

PMID- 8287316
TI  - Comparison of the suppressive effect of two doses (500 mg vs 1500 mg) of oral
      calcium on parathyroid hormone secretion and on urinary cyclic AMP.
AB  - The respective effects of the ingestion of two different doses of calcium (500
      and 1500 mg) on serum ionized calcium, intact parathyroid hormone (PTH 1-84), and
      the urinary excretion of 3',5'-cyclic adenosine monophosphate (cyclic AMP) were
      evaluated in 15 young male adults. Ionized serum calcium and PTH 1-84 were
      measured before and 1 hour, 2 hours and 3 hours (P1, P2, and P3) after the oral
      intake of calcium. Cyclic AMP was measured in 2-hour urine samples collected
      before and during 4 hours after the ingestion of calcium. Similar increments in
      serum ionized calcium (delta Ca2+) were observed except at P3 where the delta
      Ca2+ was significantly (P < 0.02) higher after 1500 mg (0.088 mmol/liter) than
      after 500 mg of (0.062 mmol/liter). In the same way, the comparison of the PTH 1
      84 concentrations showed no statistical difference except at P3 (P < 0.002). When
      expressed as a percentage of P0, the P1 and P2 PTH 1-84 values were more
      suppressed after 1500 mg than after 500 mg of calcium (P1: -69% vs -59%; P <
      0.02; P2: -66% vs -50%; P < 0.02). However, the simultaneous cyclic AMP responses
      (-24% vs -19%) were not significantly different. The results show that the
      respective maximal effects on PTH secretion and on urinary cyclic AMP of two very
      different oral doses of calcium are only slightly different.

PMID- 8287315
TI  - Decrease of serum calcium concentration and lost influence of calcium on
      parathyroid hormone release in a patient with primary hyperparathyroidism after
      treatment with diphosphonates.
AB  - Prolonged decrease of elevated serum calcium levels after treatment with
      diphosphonates in patients with primary hyperparathyroidism (pHPT) is very rare.
      A patient with water clear cell hyperplasia and five enlarged glands is presented
      who received diphosphonates (day 1 through day 8 dichloromethylene diphosphonate
      orally and a single dose of 60 mg pamidronate on day 8 intravenously) leading to
      a significant fall in serum calcium levels. Surprisingly, there was no reactive
      increase in intact parathyroid hormone (PTH) in the following 18 days. Patients
      with missing PTH regulation to hypocalcemia after diphosphonates who need a
      period of stabilization prior to parathyroid surgery might benefit most from this
      therapy.

PMID- 8287317
TI  - One-year psoas training can prevent lumbar bone loss in postmenopausal women: a
      randomized controlled trial.
AB  - On the premise that bone response to exercise is locally controlled, we conducted
      a randomized trial to evaluate the effects of a 1-year training of psoas muscles
      (treatment group: TG) versus a 1-year training of deltoid muscles (control group:
      CG) on the lumbar trabecular bone mineral density (TBMD). TBMD was measured with
      computed tomography scan. Seventy-eight subjects were included and 67 completed
      the study. Intention to treat analysis revealed no significant change in TBMD
      from 0 to 12 months. Data analysis in the 67 remaining women, including both
      assiduous and nonassiduous subjects, revealed greater bone loss in CG than in TG
      although the difference was not significant. Similar analysis in a subgroup of
      subjects who performed the exercises assiduously (TG: n = 23, CG: n = 26) showed
      that the mean bone loss of all four vertebrae from 0 to 12 months was
      significantly greater in the CG (-8.87 +/- 12.75 mg/cm3, mean +/- SD) than in the
      TG (0.14 +/- 11.21 mg/cm3, mean +/- SD, P = 0.01). These results suggest that
      continuous 1-year psoas training can prevent lumbar bone loss in postmenopausal
      women and support the hypothesis of local action of physical activity.

PMID- 8287318
TI  - Bone endothelial cells as estrogen targets.
AB  - In the present study, we investigated the effects of estrogens on bone
      endothelial cell metabolism and the presence of estrogen binding sites in the
      same cells. For these studies, we have used a continuous cell line of clonal
      bovine bone endothelial cells for evidence of a direct response to estrogens in
      vitro. Receptor analysis to intact viable cells was steroid specific and
      saturable, with an apparent dissociation constant of 17.2 nM and a Bmax of 3.2 x
      10(4) sites/cell. Northern blot analysis revealed a 6.5-kilobase mRNA that
      hybridized with a cDNA to human estrogen receptor. The 6.5-kilobase size is in
      close agreement with the reported size of the human estrogen receptor mRNA. In
      vitro estrogen responses of bone endothelial cells included a stimulation of cell
      proliferation as well as an inhibition of parathyroid hormone responsiveness.
      These findings clearly demonstrate the presence of functional estrogen receptors
      in bone endothelial cells in vitro, suggesting a role of estrogens in bone
      angiogenesis and in the entire process of bone remodeling.

PMID- 8287319
TI  - Calcium regulating activity of 24a-homo-24,24-difluoro-1 alpha,25
      dihydroxyvitamin D3 and 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin
      D3.
AB  - Two fluoro analogs of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24a-homo
      24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24aF2-homo-1,25(OH)2D3], and 26,27
      dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24F2-1,25(OH)2(Me)2D3]
      were examined for calcium (Ca)-regulating activity. The objective of the present
      study was to determine whether or not fluoro substitution at 24-position would
      alter activities of the original compounds, that is, 26,27-dimethyl 1 alpha,25
      dihydroxyvitamin. D3[1,25(OH)2(Me)2D3] and 24-homo-1 alpha,25-dihydroxyvitamin D3
      [24homo-1,25(OH)2D3], respectively. The relative activities of 24aF2-homo
      1,25(OH)2D3, 24F2-1,25(OH)2(Me)2D3, and 1,25(OH)2D3 in competing with 1,25(OH)2D3
      for binding to chick intestinal cytosol receptor were 0.28:0.5:1.0. The relative
      potencies of the same series of compounds in competition for the vitamin D
      deficient rat serum binding sites were 0.04:0.15:1. Bone-resorbing activities of
      two fluoro analogs in cultures of neonatal mouse parietal bones were more potent
      than that of 1,25(OH)2D3. Similar results were recognized in stimulating
      activities of osteoclast-like cell formation. Responses of two fluoro analogs to
      intestinal Ca absorption were similar to that of 1,25(OH)2D3. The potencies of
      1,25(OH)2D3 and its fluoro analogs in bone Ca mobilization were the highest with
      1,25(OH)2D3, followed by 24F2-1,25(OH)2(Me)2D3 and 24aF2-homo-1,25(OH)2D3, in
      that order. From these results and the data of Paulson et al., fluoro
      substitution in 24-position of 1,25(OH)2D3 apparently does not alter their
      activities,hence, the fluoro substitution at 24-position of 1,25(OH)2D3 and the
      elongation of side chain of 1,25(OH)2D3 may not intensify Ca-regulating activity.

PMID- 8287320
TI  - Fatty acid composition and arachidonic acid concentrations in alveolar bone of
      rats fed diets with different lipids.
AB  - The purpose of the present study was to determine if the type of dietary fat can
      modify the fatty acid composition and arachidonic acid levels in the alveolar
      bone phospholipids. Three groups of rats were fed nutritionally adequate
      semipurified diets containing different lipids: 10% corn oil (control, group I,
      rich in n-6 fatty acids); 9% butter + 1% corn oil (experimental, group II, rich
      in saturated fatty acids); and 9% ethyl ester concentrate of n-3 fatty acids + 1%
      corn oil (experimental, group III, rich in n-3 fatty acids). After 10 weeks of
      feeding the various diets, rats were killed, maxillae and mandibles were
      dissected out, and the soft tissue was removed. Bone was frozen in liquid
      nitrogen and pulverized. Powdered bone was extracted for total lipids, and
      phospholipids were isolated by column chromatography. The fatty acid composition
      and arachidonic acid concentrations were determined in total phospholipids after
      the addition of an internal standard, octadecatetraenoic acid (18:4n-3), and
      subsequent gas chromatography. The type of dietary lipids had a profound
      influence on the fatty acid composition of bone lipids. Arachidonic acid
      concentrations were significantly lower in total phospholipids of mandibles and
      maxillae of rats fed the experimental diets than in those fed the control diet.
      Because arachidonic acid is a precursor of prostaglandin E2 and leukotriene C4, a
      significant reduction in its concentration may result in reduced levels of these
      eicosanoids in the alveolar bone.

PMID- 8287321
TI  - Dietary lipids, prostaglandin E2 levels, and tooth movement in alveolar bone of
      rats.
AB  - A previous study showed that certain dietary lipids can alter arachidonic acid
      concentrations in alveolar bone. Because arachidonic acid is a precursor of
      prostaglandin (PG) E2, which is known to play an important role in orthodontic
      tooth movement, the purpose of the present study was to determine the effect of
      dietary lipids on PGE2 levels and tooth movement. Two groups of male Sprague
      Dawley rats (20/group) were fed nutritionally adequate purified diets containing
      10% corn oil (group I, rich in n-6 fatty acids) or 9% ethyl ester concentrate of
      n-3 fatty acids + 1% corn oil (group II rich in n-3 fatty acids). After 5 weeks
      of feeding the diets, orthodontic force of 56 g was applied to the maxillary
      incisors to tip them distally. Prior to killing the rats at day 4 and 8 of
      orthodontic force application, tooth movement was measured by computerized image
      analysis. Premaxillae were dissected out free of soft tissue and incisors. The
      alveolar bone was frozen in liquid nitrogen, pulverized, and lipids were
      extracted. The concentrations of arachidonic acid and fatty acid composition of
      total phospholipids were measured by gas chromatography. PGE2 levels were
      measured by enzyme immunoassay. Arachidonic acid and PGE2 concentration were
      significantly lower (P < 0.001) in alveolar bone of rats in group II than in
      group I. The tooth movement was also significantly lower (P < 0.02) in group II
      than in group I at both 4 and 8 days. The results suggest that PGE2 levels in
      alveolar bone and orthodontic tooth movement can be affected by the type of
      dietary fat.

PMID- 8287322
TI  - Relationships between serial blood lead levels and exfoliated tooth dentin lead
      levels: models of tooth lead kinetics.
AB  - Because bones and permanent teeth accumulate lead, exfoliated deciduous teeth
      have been utilized as retrospective markers of cumulative exposure in
      epidemiological surveys. In this paper we describe four models of lead uptake by
      the coronal dentin of shed primary teeth, each with different assumptions and
      ramifications. Each model is characterized by different relationships between
      blood lead at several ages and tooth lead. Values observed in our cohort of
      normal Boston children are most compatible with models positing the largest lead
      contribution coming at older ages (i.e., closer to age at exfoliation).
      Characteristics of models incompatible with our data include (1) lead deposition
      only during initial calcification and (2) no loss or resorption of lead.

PMID- 8287323
TI  - The aged male rat as a model for human osteoporosis: evaluation by nondestructive
      measurements and biomechanical testing.
AB  - Effects of androgen deficiency and androgen replacement on bone density, as
      measured with dual-energy X-ray absorptiometry (DXA) and single photon
      absorptiometry (SPA), cortical ratio (cortical thickness/outside bone diameter x
      100), and biomechanical properties were evaluated in 14-month-old (1 month after
      orchiectomy (orch) or sham-operation) and in 17-month-old (4 months after orch or
      sham) male rats. Whole femoral bone mineral content (BMC) and density (BMD)
      measured with DXA were not significantly decreased 1 month after orch. Whole
      femoral BMC and BMD were 10% and 8% lower in 4 months after orch (P < 0.01 and P
      < 0.001, respectively). This decrease was prevented by testosterone replacement.
      There was an excellent correlation (R = 0.99) between whole femoral BMC and
      femoral ash weight. Selective scanning of cortical and cancellous sites of the
      femur showed that both cancellous and cortical BMC and BMD were significantly
      decreased 4 months after orch. SPA of the right tibia confirmed a 7% decrease in
      cancellous BMC and BMD 4 months after orch (preventable by testosterone) but not
      in cortical BMD and BMC. Femoral cortical ratio decreased with age (47 +/- 2 in
      14-month-old and 40 +/- 2 in 17-month-old sham rats versus 63 +/- 1 in 6-month
      old male rats) due to a continuously enlarging femoral shaft. Androgen deficiency
      resulted in an even greater decrease of the cortical ratio 4 months after orch
      (36 +/- 2 in 17-month-old orch rats) that was again prevented by testosterone (47
      +/- 3).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287324
TI  - Osteoclastic resorption of Ca-P biomaterials implanted in rabbit bone.
AB  - The nature of the multinucleated cells involved in the resorption processes
      occurring inside macroporous calcium-phosphate biomaterials grafted into rabbit
      bone was studied using light microscopy, histomorphometric analysis, enzymatic
      detection of tartrate-resistant acid phosphatase (TRAP) activity, scanning, and
      electron microscopy. Samples were taken at days 7, 14, and 21 after implantation.
      As early as day 7, osteogenesis and resorption were observed at the surface of
      the biomaterials, inside the macropores. Resorption of both newly formed bone and
      calcium-phosphate biomaterials was associated with two types of multinucleated
      cells. Giant multinucleated cells were found only at the surface of the
      biomaterials; they showed a large number of nuclei, were TRAP negative, developed
      no ruffled border, and contained numerous vacuoles with large accumulation of
      mineral crystals from the biomaterials. Osteoclasts exhibited TRAP positivity and
      well-defined ruffled border. They were observed at the surface of both newly
      formed bone and biomaterials, around the implant, and inside the macropores. In
      contract with the biomaterials, infoldings of their ruffled border were observed
      between the mineral crystals, deeply inside the microporosity. The microporosity
      of the biomaterials (i.e., the noncrystalline spaces inside the biomaterials)
      increased underneath this type of cell as compared with underneath giant cells or
      to the depth of the biomaterials. These observations demonstrate that macroporous
      calcium-phosphate biomaterials implanted in bone elicit osteogenesis and the
      recruitment of a double multinucleated cell population having resorbing activity:
      giant multinucleated cells that resorb biomaterials and osteoclasts that resorb
      newly formed bone and biomaterials.

PMID- 8287325
TI  - Effects of aluminum on rat bone cell populations.
AB  - Aluminum (Al) loading is associated with reduced bone formation and osteomalacia
      in human and certain animal models. However, uncertainty exists as to the
      cellular effect(s) of Al as both inhibition and stimulation of osteoblast
      proliferation have been reported. Furthermore, the extent to which Al affects
      osteoprogenitor cell populations is unknown. To determine the cellular effects of
      Al in the rat, an animal model in which Al bone disease has been produced, we
      compared the in vitro effect of 10-50 microns Al on the proliferation and
      hydroxyproline collagen formation of marrow osteoprogenitor stromal cell
      populations and perinatal rat calvarial osteoblasts. In subconfluent cultures, Al
      suppressed proliferation of both marrow fibroblast-like stromal cells and
      calvarial osteoblasts. In confluent cultures, however, Al selectively stimulated
      periosteal fibroblast and osteoblast DNA synthesis and collagen (hydroxyproline)
      production, both in the presence or absence of 1,25-dihydroxyvitamin D.
      Osteocalcin was not detected in osteoblast-conditioned media or extracellular
      matrix. These observations suggest that the bone formation defect associated with
      Al toxicity in growing rats may be a function of impaired patterns of
      osteoprogenitor/osteoblast proliferation. Furthermore, the Al-stimulated increase
      in collagen formation is consistent with the development of osteomalacia in Al
      toxic humans and animals. The mechanism by which Al stimulated DNA synthesis and
      collagen production in more mature cultures awaits further study.

PMID- 8287326
TI  - Interleukin-11 inhibits bone formation in vitro.
AB  - The effects of interleukin-11(IL-11) on the differentiation of osteoblast
      precursors was tested using a bone nodule forming assay in rat calvaria cell
      cultures. IL-11 caused a dose dependent inhibition of nodule formation, with 500
      U/ml IL-11 resulting in complete inhibition of nodule formation. IL-11 also
      caused a reduction in alkaline phosphatase expression in these cultures. These
      effects are similar to, but more potent than, the actions of IL-6 on these cells.
      These results indicate that IL-11 is an osteotropic cytokine and suggest that IL
      11 may be an important inhibitor of bone formation in health and disease.

PMID- 8287327
TI  - Letter to my patient.

PMID- 8287328
TI  - Age and organ transplantation.

PMID- 8287329
TI  - Physicians and euthanasia.

PMID- 8287330
TI  - Compensating occupational diseases.

PMID- 8287331
TI  - Smallpox and AIDS.

PMID- 8287332
TI  - Vitamin E and dapsone-induced hemolysis.

PMID- 8287333
TI  - Food irradiation: needs discussion.

PMID- 8287334
TI  - Challenging dogma.

PMID- 8287335
TI  - Definition of gender.

PMID- 8287336
TI  - Breast cancer: can good news be news?

PMID- 8287337
TI  - Running "smokes" across the river: Canadian tobacco policy needs a boost from Mr.
      Clinton.

PMID- 8287338
TI  - Uniform requirements for manuscripts submitted to biomedical journals.
      International Committee of Medical Journal Editors.
AB  - In the 13 years since it was first published the "Uniform requirements for
      manuscripts submitted to biomedical journals" (the Vancouver style), developed by
      the International Committee of Medical Journal Editors, has been widely accepted
      by both authors and editors; over 400 journals have stated that they will
      consider manuscripts that conform to its requirements. This is the fourth edition
      of the "Uniform requirements."

PMID- 8287339
TI  - Physicians in health care management: 1. Physicians as managers: roles and future
      challenges.
AB  - Physicians are increasingly expected to assume responsibility for the management
      of human and financial resources in health care, particularly in hospitals.
      Juggling their new management responsibilities with clinical care, teaching and
      research can lead to conflicting roles. However, their presence in management is
      crucial to shaping the future health care system. They bring to management
      positions important skills and values such as observation, problem-solving,
      analysis and ethical judgement. To improve their management skills physicians can
      benefit from management education programs such as those offered by the Physician
      Manager Institute and several Canadian universities. To manage in the future
      environment they must increase their knowledge and skills in policy and political
      processes, financial strategies and management, human resources management,
      systems and program quality improvement and organizational design.

PMID- 8287340
TI  - Helicobacter pylori infection as a cause of gastritis, duodenal ulcer, gastric
      cancer and nonulcer dyspepsia: a systematic overview.
AB  - OBJECTIVE: To evaluate current evidence for a causal relation between
      Helicobacter pylori infection and gastritis, duodenal ulcer, gastric cancer and
      nonulcer dyspepsia. DATA SOURCES: A MEDLINE search for articles published in
      English between January 1983 and December 1992 with the use of MeSH terms
      Helicobacter pylori, gastritis, duodenal ulcer, gastric cancer, dyspepsia and
      clinical trial; abstracts were excluded. Six journals and Current Contents were
      searched manually for pertinent articles published in that time frame. STUDY
      SELECTION: Original studies with at least 25 patients, case reports and reviews
      that examined the relation between H. pylori and the four gastrointestinal
      disorders; 350 articles were on gastritis, 122 on duodenal ulcer, 44 on gastric
      cancer and 96 on nonulcer dyspepsia. DATA EXTRACTION: The quality of the studies
      was rated independently on a four-point scale. The strength of the evidence was
      assessed using a six-point scale for each of the eight established guidelines for
      determining a causal relation. DATA SYNTHESIS: There was conclusive evidence of a
      causal relation between H. pylori infection and histologic gastritis. Koch's
      postulates for the identification of a microorganism as the causative agent of a
      disease were fulfilled for H. pylori as a causative agent of gastritis. There was
      strong evidence that H. pylori is the main cause of duodenal ulcers not induced
      by nonsteroidal anti-inflammatory drugs, but all of Koch's postulates were not
      fulfilled. There was moderate epidemiologic evidence of an association between
      chronic H. pylori infection and gastric cancer. There was a lack of convincing
      evidence of a causal association between H. pylori and nonulcer dyspepsia.
      CONCLUSIONS: The evidence supports a strong causal relation between H. pylori
      infection and gastritis and duodenal ulcer and a moderate relation between such
      infection and gastric cancer. Further studies are needed to clarify the role of
      H. pylori in these disorders. Thus far, there is no evidence of a causal relation
      between H. pylori and nonulcer dyspepsia.

PMID- 8287341
TI  - Indications for treatment of Helicobacter pylori infection: a systematic
      overview.
AB  - OBJECTIVE: To determine (a) the advantages and disadvantages of treatment options
      for the eradication of Helicobacter pylori and (b) whether eradication of H.
      pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and
      gastric cancer. DATA SOURCES: A MEDLINE search for articles published in English
      between January 1983 and December 1992 with the use of MeSH terms Helicobacter
      pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric
      cancer, dyspepsia and clinical trial. Six journals and Current Contents were
      searched manually for pertinent articles published in that time frame. STUDY
      SELECTION: For duodenal ulcer the search was limited to studies involving adults,
      studies of H. pylori eradication and randomized clinical trials comparing anti-H.
      pylori therapy with conventional ulcer treatment. For nonulcer dyspepsia with H.
      pylori infection the search was limited to placebo-controlled randomized clinical
      trials. DATA EXTRACTION: The quality of each study was rated independently on a
      four-point scale by each author. For the studies of duodenal ulcer the outcome
      measures assessed were acute ulcer healing and time required for healing, H.
      pylori eradication and ulcer relapse. For the studies of nonulcer dyspepsia with
      H. pylori infection the authors assessed H. pylori eradication, the symptoms used
      as outcome measures and whether validated outcome measures had been used. DATA
      SYNTHESIS: Eight trials involving duodenal ulcer met our inclusion criteria: five
      were considered high quality, two were of reasonable quality, and one was weak.
      Six trials involving nonulcer dyspepsia met the criteria, but all were rated as
      weak. Among treatment options triple therapy with a bismuth compound,
      metronidazole and either amoxicillin or tetracycline achieved the highest
      eradication rates (73% to 94%). Results concerning treatment indications for
      duodenal ulcer were consistent among all of the studies: when anti-H. pylori
      therapy was added to conventional ulcer treatment acute ulcers healed more
      rapidly. Ulcer relapse rates were dramatically reduced after H. pylori
      eradication. All of the studies involving nonulcer dyspepsia assessed clearance
      rather than eradication of H. pylori. No study used validated outcome measures. A
      consistent decrease in symptom severity was no more prevalent in patients in whom
      the organism had been cleared than in those taking a placebo. Of the studies
      concerning gastric cancer none investigated the effect of eradication of H.
      pylori on subsequent risk of gastric cancer. CONCLUSIONS: There is sufficient
      evidence to support the use of anti-H. pylori therapy in patients with duodenal
      ulcers who have H. pylori infection, triple therapy achieving the best results.
      There is no current evidence to support such therapy for nonulcer dyspepsia in
      patients with H. pylori infection. Much more attention must be paid to the design
      of nonulcer dyspepsia studies. Also, studies are needed to determine whether H.
      pylori eradication in patients with gastritis will prevent gastric cancer.

PMID- 8287342
TI  - Rates and outcomes of diabetic end-stage renal disease among registered native
      people in Saskatchewan.
AB  - OBJECTIVE: To determine the rates and outcomes of diabetic end-stage renal
      disease (ESRD) among registered native people and non-native people in
      Saskatchewan. DESIGN: Retrospective population-based study using data from the
      Canadian Organ Replacement Registry. SETTING: Saskatchewan. PATIENTS: All
      patients with diabetic ESRD diagnosed between Jan. 1, 1981, and Dec. 31, 1990.
      MAIN OUTCOME MEASURES: Incidence rates of diabetic ESRD in the general
      population, rates of diabetic ESRD among patients with diabetes mellitus, nature
      of initial dialysis treatment, length of survival from start of dialysis, cause
      of death and renal transplant rates. RESULTS: The 10-year incidence rates of
      diabetic ESRD were higher among all age groups among registered native people
      than among non-native people. The overall relative risk ratio for native people
      was 16.2. When a higher prevalence of diabetes among native people was taken into
      account, native diabetic people were still seven times as likely as non-native
      diabetic people to manifest diabetic ESRD. The median survival from start of
      dialysis was under 2 years in both groups, but more native people died of stroke
      and more non-native people died of heart disease. Non-native diabetic people were
      more likely than native diabetic people to receive renal transplants.
      CONCLUSIONS: Although the overall incidence of diabetic ESRD in Saskatchewan is
      increasing, registered native people have a disproportionate risk for this
      serious complication.

PMID- 8287343
TI  - Risks and probabilities of breast cancer: short-term versus lifetime
      probabilities.
AB  - OBJECTIVE: To calculate age-specific short-term and lifetime probabilities of
      breast cancer among a cohort of Canadian women. DESIGN: Double decrement life
      table. SETTING: Alberta. SUBJECTS: Women with first invasive breast cancers
      registered with the Alberta Cancer Registry between 1985 and 1987. MAIN OUTCOME
      MEASURES: Lifetime probability of breast cancer from birth and for women at
      various ages; short-term (up to 10 years) probability of breast cancer for women
      at various ages. RESULTS: The lifetime probability of breast cancer is 10.17% at
      birth and peaks at 10.34% at age 25 years, after which it decreases owing to a
      decline in the number of years over which breast cancer risk will be experienced.
      However, the probability of manifesting breast cancer in the next year increases
      steadily from the age of 30 onward, reaching 0.36% at 85 years. The probability
      of manifesting the disease within the next 10 years peaks at 2.97% at age 70 and
      decreases thereafter, again owing to declining probabilities of surviving the
      interval. CONCLUSIONS: Given that the incidence of breast cancer among Albertan
      women during the study period was similar to the national average, we conclude
      that currently more than 1 in 10 women in Canada can expect to have breast cancer
      at some point during their life. However, risk varies considerably over a woman's
      lifetime, with most risk concentrated after age 49. On the basis of the shorter
      term age-specific risks that we present, the clinician can put breast cancer risk
      into perspective for younger women and heighten awareness among women aged 50
      years or more.

PMID- 8287344
TI  - Interleukin-4: new diabetes champion?

PMID- 8287345
TI  - Physician-assisted smoking cessation: are Canada's MDs missing the boat?

PMID- 8287346
TI  - Many Canadians unaware of AIDS' impact on women.

PMID- 8287347
TI  - An analysis of finder's fees in clinical research.

PMID- 8287349
TI  - Interns, residents take NB government to court over billing-number restrictions.

PMID- 8287348
TI  - Physicians and the pharmaceutical industry (update 1994). Canadian Medical
      Association.
AB  - The history of health care delivery in Canada has been marked by close
      collaboration between physicians and the pharmaceutical and health supply
      industries, this collaboration extending to research as well as to education.
      Since medicine is a self-governing profession physicians have a responsibility to
      ensure that their participation in such collaborative efforts is in keeping with
      their duties toward their patients and society. The following guidelines have
      been developed by the CMA to assist physicians in determining when a relationship
      with industry is appropriate. Although directed primarily to individual
      physicians, including residents and interns as well as medical students, the
      guidelines also govern the relationships between industry and medical
      associations. These guidelines focus on the pharmaceutical companies; however,
      the CMA considers that the same principles apply to the relationship between its
      members and manufacturers of medical devices, infant formulas and similar
      products, and health care products and service suppliers in general. These
      guidelines reflect a national consensus and are meant to serve as an educational
      resource for physicians throughout Canada.

PMID- 8287350
TI  - Edmonton hospital enjoys great success in weaning smokers from tobacco.

PMID- 8287351
TI  - New program helps physicians guide patients to a smoke-free future.

PMID- 8287352
TI  - CMA issues revised guidelines on physicians' relationship with pharmaceutical
      industry.

PMID- 8287353
TI  - Three-dimensional computed tomography in the head and neck diseases with bony
      abnormalities.
AB  - The purpose of this study was to define the role of three-dimensional (3D)
      computed tomography (CT) in the head and neck diseases with bony abnormalities.
      Thirty-two patients were examined with a low dose radiation technique. Three
      dimensional CT clearly delineated bony lesions in 27 of 32 patients. Three
      dimensional CT could not demonstrate subtle bony erosions infiltrated by tumor, a
      temporal bone fracture, and a blow-out fracture, although two-dimensional (2D)
      images obtained before the 3D reconstructions clearly depicted those lesions.
      These two kinds of CT technique were thought to be complimentary.

PMID- 8287354
TI  - Using kriging for 3D medical imaging.
AB  - We describe our implementation of kriging for interpolation of scalar values in
      three-dimensional medical image surface rendering and for slice interpolation.
      Kriging is an interpolation technique developed in the geosciences for estimating
      ore deposit spatial distributions. Kriging has been mathematically proven to be
      the best (statistically optimal) linear unbiased estimation technique for
      spatially distributed data. As a byproduct of the kriging technique, kriging can
      calculate the estimation error for the interslice interpolated values. Kriging
      also offers the potential for quantifying the interpolation error in slices
      computed by the estimation technique. This paper presents the initial results
      obtained using kriging for the pre-processing operations of slice interpolation
      by slice-value interpolation and interpolating voxel values during iso-surface
      extraction. We found that kriging is an accurate interpolation technique for
      surface rendering and for slice interpolation. Our results indicate that kriging
      can duplicate the rendering results obtained with other interpolation techniques
      and it offers the potential for providing visually "better" images than are
      obtained using the other interpolation techniques we tested.

PMID- 8287355
TI  - Increased blood flow in human brain tumor after administration of angiotensin II:
      demonstration by PET.
AB  - To evaluate the changes of regional cerebral blood flow (CBF) in artificial
      hypertensive state, we investigated vascular responses to changes of arterial
      carbon dioxide tension (PCO2) and blood pressure by means of positron emission
      tomography (PET). The subjects were eight brain tumors which were histologically
      proven. We calculated CBF changes in hypercapnic and hypocapnic state, and then
      using those results, CBF changes in hypertensive state were corrected. Every
      patient represented a selective increase of tumor blood flow in hypertensive
      state induced by angiotensin II, demonstrating a loss of autoregulation in tumor.
      Our results suggested the possibility of enhancement of chemotherapy for brain
      tumors.

PMID- 8287356
TI  - Intrarenal aneurysm associated with "Ask-Upmark kidney": imaging pitfalls and
      limitations.
AB  - The imaging of a case of intrarenal aneurysm with associated "Ask-Upmark kidney"
      is presented. Pitfalls and limitations encountered with imaging in this case are
      discussed. Magnetic resonance imaging (MRI) proved to be the best imaging
      modality for visualization and characterization of the mass lesions present.

PMID- 8287357
TI  - Hepatic mass in Budd-Chiari syndrome: CT and MRI findings.
AB  - We describe a case of Budd-Chiari syndrome, secondary to a hypercoagulable state,
      which produced a mass lesion on computerized tomography (CT) and magnetic
      resonance imaging (MRI) examinations. The mass simulated a tumor, but proved to
      be an area of hemorrhagic necrosis upon biopsy. The finding of a space occupying
      lesion may not always indicate a tumor in a patient with the Budd-Chiari
      syndrome. The causes, pathologic changes, and radiologic findings of Budd-Chiari
      syndrome are discussed.

PMID- 8287358
TI  - Ruptured supratentorial dermoid cysts.
AB  - Two cases with ruptured supratentorial dermoid cysts are presented. Computerised
      tomography and magnetic resonance findings are illustrated. The pathology and
      differential diagnosis is discussed.

PMID- 8287359
TI  - Bilateral obturator hernias: case report, radiographic characteristics, and brief
      review of literature.
AB  - Obturator hernia is a rare cause of intestinal obstruction, and bilateral
      obturator hernias are even rarer. Early diagnosis can decrease the morbidity and
      mortality associated with these lesions. We present the case of a patient with
      bilateral obturator hernias, discuss the radiographic findings, and briefly
      review the literature.

PMID- 8287360
TI  - Intracranial extension of basal cell carcinoma of the scalp.
AB  - A case of recurrent basal cell carcinoma of the right occipital scalp is
      reported. Plain film, CT, and MRI examinations of the head demonstrated direct
      neoplastic invasion through the occipital bone and meninges into the right
      cerebellar hemisphere.

PMID- 8287361
TI  - Aromatic DNA adducts in brain tumors by 32P-postlabeling analysis.
AB  - DNA from human brain tumor samples was analysed by the 32P-postlabeling technique
      for the presence of aromatic DNA adducts. Thirteen out of 16 samples showed low
      levels of adducts at 0.14-3.53 adducts per 10(9) nucleotides. Inter-individual
      variations in the patterns of these aromatic adducts were observed. On the other
      hand, none of 5 brain samples from epilepsy patients revealed any evidence of
      such adducts. The data demonstrated the presence of low level, large molecule
      aromatic DNA adducts in malignant brain tissues and these adducts may either
      result from environmental exposure to an undetermined genotoxic agent or from the
      aging process.

PMID- 8287362
TI  - Carcinogenic effects in rats of nitrosopiperazines administered intravesically:
      possible implications for the use of piperazine.
AB  - Two nitrosamines derived from nitrosation of piperazine, 1-nitrosopiperazine (NO
      PIP) and 1,4-dinitrosopiperazine (DNP), were administered to groups of twelve
      female F344 rats intravesically. The doses were, respectively, 40 mg and 5.2 mg
      twice a week for 48 and 36 weeks in aqueous solution. Ten DNP-treated animals
      survived the treatment; six had tumors related to the treatment, nasal mucosa
      adenocarcinomas or neuroblastomas in five and a transitional cell carcinoma of
      the bladder in one. Rats treated with NO-PIP received a ten times greater dose,
      and all died by week 59, two with transitional cell neoplasms of the bladder and
      four with carcinomas of the nasal mucosa. NO-PIP was probably in part converted
      by transnitrosation to DNP. Piperazine, widely used as an oral anti-helminthic,
      could interact with nitrosating agents in vivo to form the two nitrosamines here
      shown to pose a possible carcinogenic risk if present in the bladder, by
      absorption through the bladder wall.

PMID- 8287363
TI  - Genotoxic effects of nicotine in combination with arecoline on CHO cells.
AB  - Genotoxic effects of nicotine and arecoline, major alkaloids of tobacco and areca
      nut, respectively, were analysed in combination on CHO cells utilising two
      different cytogenetic end points, namely chromosome aberration frequency and
      sister chromatid exchange frequency. Statistically significant elevation in the
      values of both markers compared with controls, as well as nicotine alone, clearly
      indicated a more clastogenic and genotoxic effect following the addition of areca
      nut to tobacco. The effects observed following the treatment with a low dose for
      a longer duration are of relevance to the condition of oral mucosa of the chewers
      of tobacco with areca nut.

PMID- 8287364
TI  - Covalent binding of (+) 7S-trans-7,8-dihydrobenzo [a]pyrene-7,8-diol to trout
      DNA: P-450- and peroxidation-dependent pathways.
AB  - Bioactivation in vivo of pure (+) 7S-trans-7,8-dihydrobenzo[a]pyrene- 7,8-diol
      ((+) BP-7,8-DHD) was investigated in rainbow trout. Embryos, microinjected with
      0.01-1.0 microgram of [3H]-(-)-7S-trans-7,8-dihydrobenzo[a]-pyrene-7,8-diol-anti
      9,10-epoxide ((-) anti-BPDE), exhibited a dose-dependent increase in DNA
      adduction. Subsequently, microinjection of trout embryos with [14C] (+) BP-7,8
      DHD also demonstrated a dose-dependent increase in DNA adduction. To determine
      the relative contribution of P-450-dependent versus peroxidation-dependent
      epoxygenation of (+)-BP-7,8-DHD, trout embryos were co-injected with [14C]-(+)-BP
      7,8-DHD and either beta-naphthoflavone (BNF) (CYP1A1 inducer) or carbon
      tetrachloride (CCl4) (lipid peroxidation enhancer). Co-injection with BNF tended
      to enhance covalent binding to DNA, which was consistent with rapid induction of
      CYP1A1. Co-injection with CCl4, significantly increased covalent binding of [14C]
      (+)-BP-7,8-DHD to DNA, suggesting a contribution from non-enzymic cooxidation.
      32P-Postlabeling analysis of liver DNA adducts following i.p. injections of (+)
      BP-7,8-DHD did not detect appreciable amounts of (-) anti-BPDE-dG from juvenile
      trout fed control diets or diets containing hydrogen peroxide or BNF. On the
      contrary, BNF pre-feeding markedly enhanced the levels of an adduct which co
      chromatographed with authentic (+) syn-BPDE-dG. These results confirm that trout
      are capable of metabolically activating BP-DHD to the ultimate carcinogen BPDE
      and that BNF stimulates CYP1A1-dependent epoxygenation, but peroxidation
      dependent activation may not contribute significantly to the bioactivation of BP
      7,8-DHD in vivo.

PMID- 8287365
TI  - Establishment of lung cancer cell line producing parathyroid hormone-related
      protein.
AB  - Parathyroid hormone-related protein (PTHrP) producing cell line (KCC-C1) was
      established from malignant pleural effusion of a patient with squamous cell lung
      carcinoma. Hypercalcemia and granulocytosis were noted in the patient. The serum
      level of PTHrP, measured by N-terminal specific radioimmunoassay, was 110 pg/ml
      (normal < 20 pg/ml). The established KCC-C1 tumor cells proved to have PTHrP RNA
      transcripts and produce a large amount of PTHrP. Besides the production of PTHrP,
      the culture medium contained a significant level of interleukin 1 (IL-1).
      However, tumor necrosis factor or colony stimulating factor was not defected.
      Transplantation of KCC-C1 tumor cells into nude mice resulted in tumor formation
      with hypercalcemia. As IL-1 is also known to have bone-resorbing activity, KCC-C1
      which may prove valuable in the study of the interaction between PTHrP and IL-1
      for induction of hypercalcemia.

PMID- 8287366
TI  - Nucleolar and nuclear aberrations in human lox tumor cells following treatment
      with p120 antisense oligonucleotide ISIS-3466.
AB  - Previous reports from this laboratory have shown marked cytocidal effects of the
      ISIS-3466 antisense phosphorothioate oligodeoxynucleotide to the human nucleolar
      protein p120 on human cancer cell lines in vitro and inhibition of tumor growth
      in vivo in an i.p/i.p. LOX cell model (L. Perlaky et al. Anti-Cancer Drug Design
      8:3-14, 1993). In this study, light and fluorescence microscopy showed that the
      number of LOX cells in mitosis decreased by 50% after incubation for 4 h in 0.2
      0.4 microM antisense oligonucleotide; a 70% reduction in cell number was found
      from 8-72 h post-treatment. In addition, marked unravelling of nucleolar
      structures and chromatin fragmentation was found after a 4-h incubation. The
      nucleolar unravelling occurred in varying degrees ranging from partial unfolding
      to almost complete separation of the strands of nucleolar residues. Twenty four
      hours post-treatment, immunofluorescence staining with the anti-p120 monoclonal
      antibody showed reduced nucleolar protein p120 and translocation of the p120
      protein from the nucleoli to the nucleoplasm. Analysis of the mechanisms of the
      nucleolar unravelling and inhibition of mitosis will provide further
      understanding of the cytocidal effects of the ISIS-3466 antisense
      oligonucleotide.

PMID- 8287367
TI  - Clonal growth and origin of two human keratinocyte cell lines transformed by
      human papillomavirus type 16 DNA.
AB  - Two human keratinocyte cell lines transformed by human papillomavirus type 16,
      designated Vp and Up, were compared for their clonal growth potential and clonal
      origin. Up showed greater anchorage-independent growth in soft agar and higher
      efficiency of single-cell colony formation than Vp (24.3% compared to
      approximately 10%). The clonal growth potential of these two cell lines was not
      related to the level of HPV16 gene expression. Fourteen single cell clones of the
      Vp and 24 of the Up were selected, propagated and analyzed by Southern and
      Northern blot analysis. Clonal variations existed among subclones of each cell
      line and between the two cell lines. These variations included cell morphology,
      growth potential, and expression levels of involucrin (a differentiation marker
      of keratinocytes) and of HPV16 mRNAs. The Vp and Up cell lines also showed
      different patterns of HPV16-DNA integration and RNA transcription. However, all
      subclones of Vp and subclones of Up displayed identical HPV16 DNA integration and
      RNA expression patterns. The results suggest that both cell lines were monoclonal
      in origin and that the host genetic factors play an essential role in determining
      cell clonality.

PMID- 8287368
TI  - Morphological transformation of C3H10T1/2CL8 cells by cyclopenta-fused
      derivatives of benzo[a]pyrene and benzo[e]pyrene.
AB  - Cyclopenta-fused homologs of polycyclic aromatic hydrocarbons (PAH) have proven
      to be more genotoxic and tumorigenic than their parent PAHs. In an effort to
      uncover their mechanisms of metabolic activation, the morphological transforming
      activities of dibenzo[k,mno]acephenanthrylene (CP(3,4)B[a]P),
      dibenzo[j,mno]acephenanthrylene (CP(1,12)B[a]P) and naphtho[1,2,3,4
      mno]acephenanthrylene (CPB[e]P) were studied in C3H10T1/2CL8 mouse embryo
      fibroblasts. CP(3,4)B[a]P, a PAH with a blocked K region and unblocked bay
      region, was highly active inducing an average of 1.1 Type II and III foci/dish at
      5 micrograms/ml with an average of 67% of the dishes containing foci. This
      activity was similar to that of benzo[a]pyrene. CP(1,12)B[a]P and CPB[e]P were
      inactive. The relative positions of the cyclopenta-ring and bay region may play
      an essential role in the metabolic activation of these PAHs and their biological
      activities.

PMID- 8287369
TI  - Morphological transformation of Syrian hamster embryo cells in primary culture by
      malachite green correlates well with the evidence for formation of reactive free
      radicals.
AB  - Malachite green (MG) (green crystals with metallic luster and very soluble in
      water) is highly cytotoxic to mammalian cells and also acts as a liver tumor
      promoter. In view of its industrial importance and possible exposure to
      individuals, MG poses a potential environmental health hazard. We have studied
      the effect of MG on the formation of morphologically transformed colonies using
      Syrian hamster embryo (SHE) cell transformation assay. MG induced a dose-related
      increase in the formation of transformed foci, the optimum concentration being
      0.05 micrograms/ml. Electron spin resonance (ESR) analysis using 5,5-dimethyl-1
      pyrroline N-oxide (DMPO) as a spin-trapping agent showed the formation of
      reactive free radicals during the in vitro metabolism of MG. The present study
      suggests a close relationship between the morphological transformation of SHE
      cells by MG and the possible involvement of reactive free radical formation.

PMID- 8287370
TI  - Inhibition of MDR1 gene expression by H-87, a selective inhibitor of cAMP
      dependent protein kinase.
AB  - N-[2-(p-bromocinnamylmethylamino) ethyl]-5-isoquinolinesulfonamide (H-87), a
      newly synthesized inhibitor of protein kinase A, significantly decreased the drug
      resistance of multidrug resistant human U937/M cells, mouse FM3A/M and P388/M
      cells. Northern blot analysis showed MDR1 gene expression was decreased in H-87
      treated P388 M cells. H-87 inhibited the activity of MDR1 (multidrug resistance
      1) promoter in a dose-dependent manner in transient expression assay. In
      contrast, the expression of c-raf-1 gene significantly enhanced the activity of
      MDR1 promoter. We therefore examined the effect of H-87 on MDR1 gene expression
      in c-raf-1 transfected CV-1 cells (CV-1/raf). A significant decrease in the level
      of MDR1 mRNA was observed after H-87 treatment of the CV-1/raf cells. These
      results suggest that inhibition of MDR1 gene expression by H-87 is associated
      with circumvention of drug resistance in MDR cells.

PMID- 8287371
TI  - Correlation of mitotic abnormalities and the presence of human papillomavirus
      antigens in squamous cell carcinomas of the oral cavity.
AB  - To determine the association of human papillomavirus (HPV) with oral cancer
      lesions containing abnormal mitoses, we analysed 54 of them by
      immunohistochemical techniques for the presence of HPV structural antigens and
      correlated the results with their histology. Sixteen out of 19 lesions with
      abnormal mitotic figures (MFs) and 15 of the 25 lesions with normal MFs contained
      the HPV antigen. However, 9 of the 11 koilocytotic lesions with abnormal MFs and
      13 of the 17 lesions with normal MFs were HPV antigen-positive. The nature of
      mitosis was not influenced by the grades of koilocytosis. No correlation of HPV
      antigen positivity and severity of the oral carcinomas was observed.

PMID- 8287372
TI  - Lipids alter the level and distribution of mouse mammary tumor virus gp52 in
      vitro.
AB  - Linoleic acid, cholesterol, dexamethasone and progesterone were tested by
      immunocytochemistry and immunoprecipitation for their single and combined effects
      in vitro on mouse mammary tumor virus (MMTV) gp52 distribution among three
      compartments: cell-associated antigen, extracellular virus particles and
      extracellular shed antigen unassociated with virus particles. Results indicated
      that all additives significantly increased total MMTV gp52 levels and altered the
      distribution. Linoleic acid and dexamethasone induced the greatest relative
      proportion of extracellular gp52, whereas cholesterol and progesterone induced
      the greatest proportion of cell-associated gp52. The implications of these
      findings for the immune response to mammary tumors is discussed.

PMID- 8287373
TI  - Morphological and morphometric measurements in colorectal mucosa of subjects at
      increased risk for colonic neoplasia.
AB  - Measurements of intermediate biomarkers have recently increased, attempting to
      provide useful information about cancer risk. We report morphological findings in
      rectal mucosal biopsies from patients at low risk and at high risk for colorectal
      cancer. Rectal biopsies were analyzed from fourteen Seventh-Day Adventist (SDA)
      subjects at low risk and from twenty-seven members of families with hereditary
      nonpolyposis colonic cancer (HNPCC) at higher risk. The following measurements
      were made on rectal crypts: length of crypts, numbers of cells, diameter of the
      surface, middle and base of the crypts and infiltration of inflammatory cells
      into the lamina propria. Findings indicated morphological differences in normal
      appearing rectal mucosa of individuals in the HNPCC group compared with SDA
      subjects (P < 0.05). They included shorter crypts with fewer epithelial cells and
      increased cellular infiltration in the mucosa of HNPCC subjects compared with SDA
      subjects, suggesting minimal inflammation, and an early stage of crypt atrophy in
      the rectal mucosa of subjects at higher risk for colonic neoplasia.

PMID- 8287374
TI  - Synergistic induction of rat microsomal CYP1A1 and CYP1A2 by acetone in
      combination with pyridine.
AB  - The effect of exposure to acetone, pyridine or acetone in combination with
      pyridine on microsomal CYP1A1, CYP1A2 and CYP2E1 levels and their catalytic
      activities was determined in the rat. CYP1A1 and CYP1A2 in the liver and CYP1A1
      in the lung were induced along with their catalytic activities by either
      pyridine, acetone or acetone and pyridine. The induction by acetone and pyridine
      was greater than the additive effect of both compounds, indicating synergism.
      Acetone, pyridine or both compounds induced CYP2E1 protein to the same extent in
      the liver and lung. However, induction of CYP2E1 protein was accompanied by
      induction of its catalytic activity in the liver but not in the lung. This is the
      first reported induction of CYP1A proteins and catalytic activities (a) by
      acetone and (b) synergistically by xenobiotics.

PMID- 8287375
TI  - Regulation of HIV-1 LTR trans-activating activities in two different human
      hepatocellular carcinoma cell lines.
AB  - The regulation of trans-activating activities of two human hepatocellular
      carcinoma cell (HCC) lines, HEP-G2 and SK-HEP-1, was investigated. These cells
      were transfected with the wild-type and a nested series of its 5'-deletion
      mutants of the long terminal (LTR) repeat derived from HIV-1, which were ligated
      with the chloramphenicol acetyl transferase gene. These two HCC cell lines
      exhibited different biological characteristics, reflecting their status of
      differentiation. Both cell lines showed moderate degrees of constitutive (basal)
      trans-activating activities. While HEP-G2 cells, which are well differentiated,
      showed marked degrees of enhancement of trans-activation after treatment with 12
      O-tetradecanoylphorbol-13-acetate, SK-HEP-1 cells, which are poorly
      differentiated, showed only moderate or low degrees of enhancement. These two
      cell lines up-regulated their trans-activating activities in response to the
      deletion of some regions of positive and negative regulatory elements, suggesting
      that they produce trans-acting factors that are quantitatively different from
      each other, and often employ different sets of positive and negative regulatory
      elements for trans-activation.

PMID- 8287377
TI  - Occurrence and de novo biosynthesis of follicle stimulating hormone (FSH) in
      benign and malignant conditions of human breast.
AB  - We report the occurrence as well as biosynthesis of a pituitary hormone, follicle
      stimulating hormone (FSH) in human breast. Using immunoperoxidase localization
      technique, both FSH and beta-FSH were localized in cytoplasm of epithelial cells
      but not in stromal cells. Immunostaining was more intense in benign and malignant
      specimens as compared to normal. In vitro radiolabelled precursor experiments
      with breast tissue explants indicate de novo synthesis of FSH. Human milk had
      higher concentrations of FSH as compared to serum. In gonads, FSH is involved in
      the cellular growth, differentiation and function. The presence of higher levels
      of FSH in benign mammary tumors and breast cancer when compared to normal breast
      supports the suggestion that FSH might have a role in the process of breast
      malignant transformation.

PMID- 8287376
TI  - Impact of organosulfur compounds in garlic on canine mammary tumor cells in
      culture.
AB  - Six organosulfur compounds found in garlic were examined for their ability to
      alter the growth of canine mammary tumor cells (CMT-13) in culture. Water-soluble
      organosulfur compounds (S-allyl-cysteine, S-ethyl-cysteine and S-propyl-cysteine)
      did not significantly alter the growth of CMT-13 cells when added to cultures at
      1.0 mM or less. However, oil-soluble organosulfur compounds (diallyl sulfide,
      diallyl disulfide and diallyl trisulfide) markedly inhibited growth. Increasing
      addition of diallyl disulfide (DADS) resulted in a progressive decrease in CMT-13
      cell growth. Addition of glutathione before DADS markedly decreased the severity
      of the growth inhibition. Treatment with DL-buthionine-SR-sulfoxamine, a specific
      inhibitor of glutathione synthesis, accentuated the growth inhibition caused by
      DADS. These studies show that some organosulfur compounds found in garlic are
      effective inhibitors of the growth of the neoplastic CMT-13 cell. The inhibitory
      effects of these compounds are modified by intracellular glutathione.

PMID- 8287378
TI  - Estrous cycle modulation of O6-alkylguanine-DNA alkyltransferase expression in
      rat mammary epithelial cells.
AB  - N-methyl-N-nitrosourea (MNU)-induced rat mammary tumor incidence and tumor number
      per rat, is directly correlated with an increase in the circulating level of
      estrogen(s) at the time of carcinogen administration and subsequent mammary
      epithelial O6-methylguanine content. We report that, expression of O6
      alkyltransferase (AGT) is also regulated by reproductive hormones in a tissue
      specific manner. The level of mammary epithelial cell AGT activity on estrus
      (0.47 pmol/mg protein) and proestrus (0.32) was significantly higher than on
      metestrus (0.14) (P < 0.05, estrus vs. metestrus). However, no change was
      observed in liver AGT activity (0.52 pmol/mg protein). In contrast, the mean
      level of AGT protein was not significantly different between tumors from rats
      injected with MNU on different days of the estrous cycle. In conclusion, the
      different tumor biologies resulting from carcinogen injection on different days
      of the estrous cycle may be partially explained by variation in levels of DNA
      repair activity. However, the cells in the resulting tumors did not continue an
      obligatory differential expression of the AGT activity consistent with their
      stage of initiation.

PMID- 8287379
TI  - Biological activity of a K-ras mutant that contains the 12R/59T/116Y mutations.
AB  - The 12R/59T/116Y mutations have been shown to confer a dominant negative activity
      on H-ras oncogene (H-ras 116Y). To determine whether this event is unique for H
      ras, we introduced the same mutations into K-ras oncogene. This mutant, K-ras
      116Y, suppressed transformed phenotypes induced by overexpression of H-ras proto
      oncogene. NIH3T3 cells expressing K-ras 116Y were resistant to transformation by
      v-fes oncogene. Analysis of chimaeras between H- and K-ras 116Y showed that the C
      terminal variable region determines the level of suppressor activity. These
      results suggest that these mutations are applicable to other GDP/GTP binding
      proteins.

PMID- 8287380
TI  - Effects of capsaicin on liver microsomal metabolism of the tobacco-specific
      nitrosamine NNK.
AB  - Chemically-induced mutagenesis and carcinogenesis is modulated by various plant
      products, some of which are present in the human diet. 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK), a potent carcinogen in tobacco and tobacco smoke, is
      activated by microsomal enzymes. In this study, we investigated the effects of
      capsaicin on the in vitro metabolism of NNK. Capsaicin is the principal component
      of Capsicum fruits used widely by humans as a food additive. Liver microsomes
      from saline-injected, phenobarbital-induced and beta-naphthoflavone-induced
      hamsters were used. Microsomes from phenobarbital and beta-naphthoflavone-induced
      animals expressed decreased NNK reduction and enhanced pyridine-N-oxidation, but
      did not significantly alter alpha-carbon hydroxylation of NNK. Capsaicin (0.5 mM)
      inhibited the formation of all metabolites of NNK by all microsomal fractions and
      inhibited alpha-hydroxylation by phenobarbital-induced microsomes more than by
      either of the other two treatments. Our results suggest that capsaicin, as a
      naturally occurring dietary constituent, possesses antimutagenic and
      anticarcinogenic properties through the inhibition of xenobiotic metabolizing
      enzymes.

PMID- 8287381
TI  - Potential synergism between wheat bran and psyllium: enhanced inhibition of colon
      cancer.
AB  - In this study we compared the influence of high fat (20% w/w) diets that combine
      low levels of calcium (0.18% w/w) and low (1% w/w), medium (4% w/w) and high (8%
      w/w) levels of dietary fiber from wheat bran (WB), with high (8% w/w) levels of
      dietary fiber from psyllium (PS) alone or in various combinations with WB, on the
      induction of colon tumors in Fischer-344 rats following exposure to azoxymethane
      (AOM). The rats were fed the experimental diets for 2 weeks, and then were given
      two s.c. injections of AOM (15 mg/kg body wt./week). Twenty-three weeks following
      the first injection of AOM, the incidence of colon tumors in the different
      dietary groups (12 rats/group) was compared. The results clearly showed that by
      increasing the dietary fiber concentration of WB from 1 to 8% significantly
      reduced the number of colon tumors/group. When the influence of 8% dietary fiber
      from WB on the development of colon tumors was compared with that of PS (WB:PS =
      0:100), no significant difference was observed. However, combinations of WB and
      PS showed a greater protective effect than either WB or PS alone, at comparable
      levels of dietary fiber. The 50:50 combination of WB and PS showed maximum
      protection, while 25:75 and 75:25 combinations both produced intermediate
      effects. None of the diets showed any significant effect on the normal growth of
      rats. The results indicate that WB and PS fiber alone, and to a greater degree in
      combination, can offer protection against colon cancer promoted by high fat, low
      calcium diets. Diets that include wheat bran in combination with psyllium could
      be an effective means of reducing colon cancer risk in human populations addicted
      to high risk western diets.

PMID- 8287382
TI  - The B chain, but not the A chain, of Ricinus communis activates human complement.
AB  - Complement activation properties of ricin holotoxin, its A or B chain were
      assessed in two enzyme immunoassays (EIA). One was specific for C3 activation
      products and the other detected the terminal SC5b-9 complement complex (TCC) and
      thus determined activation of the initial and terminal part of the complement
      pathways, respectively. Ricin and its A and B chains were incubated with normal
      human serum or EDTA-serum. It was found that ricin B chain activated both the
      initial and terminal complement pathways in a time- and concentration-dependent
      fashion, whereas the A chain and the holotoxin did not.

PMID- 8287383
TI  - Uptake and distribution of intravenously or intravesically administered
      photosensitizers in the rat.
AB  - Photodynamic therapy using i.v. injected porphyrin photosensitizers have been
      used to treat selected cases of superficial bladder cancer. Since cutaneous
      photosensitivity, lasting 6-8 weeks, is a well known undesirable side effect of
      this therapy, we instilled the photosensitizers intravesically in rats and
      compared the uptake of photosensitizers in different tissues by this route of
      administration with the uptake after intravenous injection. The intravesical mode
      of delivery enhanced photosensitizer uptake in the bladder wall, while giving low
      concentrations in extravesical organs. Intravesical instillation of the
      photosensitizers may therefore increase their efficacy and reduce phototoxicity
      as compared with intravenous injection. Comparing the results obtained by two
      assays, one based on porphyrin fluorescence and the other based on the
      application of radioactively labelled photosensitizers, it was concluded that the
      i.v. administration route may result in tissue uptake of significant amounts of
      aggregated non-fluorescent, supposedly inactive drug, while the intravesical
      administration led to less uptake of aggregates relative to active drug monomers.

PMID- 8287384
TI  - [The noninvasive assessment of coronary flow during isometric exercise by Doppler
      ultrasonography of the internal mammary artery anastomosed to the left coronary].
AB  - Isometric contraction of small group of muscles is believed to increase heart
      rate and contractility and arterial pressure without significant changes in
      systemic arterial resistance. Such a manoeuvre has been employed in this work to
      study dynamic changes induced in blood flow into coronary bed, in subjects in
      which an anastomosis of the internal mammary artery to anterior descending
      coronary artery was performed. Ten patients with no clinical signs of myocardial
      ischaemia at rest and during exercise, were requested to perform an endurance
      left handgrip manoeuvre, at 50% of maximal voluntary contraction. Doppler blood
      velocity curve in the anastomosed mammary artery; non-invasive blood pressure
      curve at a finger of the right hand by Finapres; the electrocardiogram, were
      recorded. A significative increase in heart rate and mean and diastolic blood
      pressure was found. Blood flow significantly increased, approximately in the same
      percentage as double product was increased. A calculated index of coronary
      resistance did not show significant changes. In this group of patients, the
      handgrip manoeuvre may display the ability of the cardiac pump to match its
      metabolic needs due to increased pressure load, by employing the same developed
      pressure load as an adequate coronary perfusion pressure. It is suggested to
      employ this simple test in the routine monitoring of patients with internal
      mammary artery bypass grafts.

PMID- 8287385
TI  - [The immediate and long-term efficacy of electrical cardioversion in atrial
      fibrillation].
AB  - With the aim to identify short- and long-term features predictive of successful
      electric cardioversion in stable atrial fibrillation, 186 consecutive patients
      submitted to electric cardioversion were reviewed. The following parameters were
      considered: age, atrial fibrillation duration, previous atrial fibrillation
      episodes, echocardiographic left atrial diameter, pre-treatment and prophylaxis
      with amiodarone. The patients were divided in 3 groups: Group I included 97
      patients with mitral valve disease or mitral prosthesis, Group II included 27
      patients with lone atrial fibrillation and Group III included 62 patients with
      different heart and extracardiac diseases. The electric cardioversion restored
      sinus rhythm in 155 patients (83%). The failure of the electric cardioversion was
      related only to a longer atrial fibrillation duration and to pre-treatment with
      amiodarone. Moreover, the failure of the electric cardioversion was more frequent
      in Group II patients (with lone atrial fibrillation) than in Group I patients
      (mitral disease or prosthesis; p < 0.005). Only for Group I patients failure of
      the cardioversion was related to a larger left atrium diameter (p < 0.05). Eighty
      nine (57%) of the 155 patients converted to sinus rhythm were followed for at
      least 1 year. At 1 year sinus rhythm persisted in 57 patients (64%), and
      prophylaxis with amiodarone was the only predictor of sinus rhythm persistence (p
      < 0.05). Out of 68 patients with a 3 year follow-up, 29% still showed sinus
      rhythm after a single cardioversion and 37% after 2 or more cardioversions; after
      5 years, out of 58 patients, those showing sinus rhythm were 6 (10.3%) and 9
      (16%) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287387
TI  - [The usefulness of bioimpedance in patient monitoring in an intensive-therapy
      heart-surgery unit: a comparison with thermodilution].
AB  - Haemodynamic monitoring of intensive care unit (ICU) patients can be carried out
      by thermodilution system. This method is invasive, does not give a continuous
      monitoring and complications can occur. Thoracic electrical bioimpedance (TB), a
      non invasive, fast, easily repeatable method, is able to measure some important
      haemodynamic parameters: end diastolic volume (EDV), stroke volume, cardiac
      output (CO), ejection fraction (EF), some contractility indexes, systemic
      vascular resistances (SVR) and cardiac work. The aim of the present study is to
      compare CO and SVR obtained by thermodilution with the same indexes obtained by
      TB. Therefore, 20 ICU patients (12 males and 8 females, mean age 54 +/- 11 years)
      were studied. Out of them, 16 had been submitted to cardiac surgery in the
      previous 7 days and 4 were waiting for cardiac surgery. The patients were divided
      in 2 groups: Group A (N 4) included patients with valvular malfunction and/or
      cardiac arrhythmias and Group B (N 16) included patients with normal valvular
      function and sinus rhythm. CO obtained by TB was well related with the one
      obtained by invasive (INV; r = 0.878; p < 0.001). The mean value of difference of
      the 2 methods was 12.29 +/- 11.83 for the whole group of 20 patients but it was
      26.07 +/- 14.16 in the Group A and 8.84 +/- 8.09 in the Group B confirming the
      less reliability of the method in patients with abnormal valvular function or in
      the presence of cardiac arrhythmias. As a consequence, SVR obtained by TB and INV
      resulted well related (r = 0.752; p < 0.001). The mean value of differences was
      11.14 +/- 9.01 in the group of 20 patients and particularly 19.55 +/- 10.87 in
      the Group A and 9.04 +/- 7.07 in the Group B. In a subgroup of 9 patients, CO was
      measured at successive times (0, 30, 60, 90 min) by both TB and INV; when
      comparing the 2 CO values a significant correlation was observed. In conclusion,
      TB represents a valid method in haemodynamic monitoring of the ICU patients.

PMID- 8287386
TI  - [An algorithm for the analysis of the circadian profile of the arterial pressure
      in normotensive subjects].
AB  - In this paper we proposed the use of a spectral analysis technique, the fast
      Fourier transform (FFT), for the evaluation of the normal circadian blood
      pressure rhythm. By means of this algorithm it is possible to separate the slower
      and reproducible variations of the blood pressure profile (probably due to
      endogenous rhythm) from the faster and random ones (due to psychophysical status
      of the subject). The FFT technique is used for the analysis of ambulatory blood
      pressure monitorings obtained in 66 normotensive subjects (38 males and 28
      females, mean age 35 +/- 10 years). Taking into account the mean duration of
      pressure variations related to major daily activities (e.g. sleeping, eating,
      etc) it is proposed to consider the first 10 harmonics as those having the main
      influence on the circadian blood pressure rhythm. The amplitude of the first 10
      harmonics of the whole sample was evaluated by using the chi 2 and the Kolmogorov
      tests, and the results confirmed the assumption of a normal distribution of the
      amplitudes. The 95% confidence interval of these harmonics was chosen as the
      criteria for defining a normal range for the circadian blood pressure rhythm.
      This approach was tested in a group of 4 hypertensive patients showing that
      alteration of the circadian blood pressure rhythm can be easily diagnosed.

PMID- 8287388
TI  - [A reduction of left ventricular hypertrophy and an improvement in diastolic
      function after therapy with nifedipine retard in patients with hypertensive
      cardiopathy].
AB  - Left ventricular (LV) hypertrophy with increased LV mass is associated with
      abnormal LV diastolic filling in patients with hypertension. To assess the effect
      of antihypertensive therapy on LV mass (M), LV wall stress (SS) and rapid LV
      filling, 16 patients (12 males, 4 females), mean age 57 +/- 8 years, were treated
      with nifedipine slow release (NSR, 20 mg bid) for 12 months and evaluated by
      Doppler echocardiography at baseline and at 3, 6, 9, 12 months from the beginning
      of treatment. No other cardiovascular drugs were given during the study. Systolic
      and diastolic blood pressure (SBP, DBP), LVM/m2 body surface (bs; M/m2), LVSS, LV
      end-diastolic and end-systolic diameters (EDD/m2, ESD/m2) bs, left atrial
      diameter (LAD), fractional shortening index (FS%), isovolumic relaxation time
      (IVRT), E/A velocities ratio at mitral Doppler spectrum (E/A) were measured at
      each examination. During treatment, systolic and diastolic blood pressure, LVM,
      LVSS, LV end-systolic diameter and isovolumic relaxation time decreased and FS%
      and E/A significantly increased as compared with baseline values, EDD and LAD did
      not change significantly. The reduction of LVSS was of greater extent compared
      with that of LVM, at short and at mid-term, probably for a fibrotic component of
      LVM induced by chronic systolic overload. Changes of ESD and FS% were less
      evident compared with LVSS, possibly depending on their contribution to LVSS
      normalization. In conclusion, our experience indicates that NSR is an effective
      antihypertensive agent at short and mid-term.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287389
TI  - [Treatment strategies in acute heart failure: how to restore hemodynamic
      stability rapidly and safely].

PMID- 8287390
TI  - Successful treatment of coronary artery spasm following coronary artery bypass
      grafting.
AB  - A case of coronary artery spasm developed 6 hours after myocardial
      revascularization inducing both hemodynamic and electrocardiographic changes, is
      reported. The spasm was documented by coronary angiography, and it was not
      reversed by intracoronary infusion of isosorbide dinitrate. Intravenous infusion
      of nifedipine (initial dose of 0.0104 mg/min to final dose of 0.0208 mg/min),
      along with infusion of glyceronitrate (1.0 micrograms/kg/min) was able to
      significantly improve hemodynamic impairment and to reverse electrocardiographic
      changes in 12 hours. Coronary angiography, repeated in postoperative day 3, after
      48 hours of continuous nifedipine infusion, showed a resolution of coronary
      spasm. There was no evidence of myocardial infarction as resulted from total CPK
      and MB isoenzyme release. Nifedipine infusion was gradually reduced as oral
      administration of slow release nifedipine (40 mg twice daily) was started. The
      combined intravenous infusion of glyceronitrate and nifedipine seems to be able
      to control and overcome coronary artery spasm following coronary surgery.

PMID- 8287391
TI  - Recent cardiovascular drugs from Chinese medicinal plants.
AB  - This paper describes the pharmacology of some recent cardiovascular drugs derived
      from plants used in Chinese traditional medicine. The groups of compounds
      discussed are benzylisoquinolines (several), tetrahydropyrazine (also called
      ligustrazine), rhynchophylline and hirsutine, ginkgolides and other PAF
      inhibitors, coumarins, and ginsenosides, plus a miscellaneous group;
      approximately 30 substances in all. The plant sources and the pharmacology are
      indicated for the drugs in each group. By far the most studied compounds are the
      benzylisoquinolines, especially tetrandrine. The types of pharmacological
      activity recently described for cardiovascular drugs from plants include calcium
      antagonism, adrenoceptor antagonism, antagonism of platelet activating factor
      (PAF), and the ability to act as antioxidants. Hundreds of chemicals have been
      isolated and identified as constituents of thousands of plants but the basic and
      clinical pharmacology is known for only a handful of these drugs. Much more
      research is needed, especially with regard to the pharmacology, both basic and
      clinical, of the pure chemicals derived from plants.

PMID- 8287392
TI  - "Wavefronts" in the aorta--implications for the mechanisms of left ventricular
      ejection and aortic valve closure.
AB  - Our understanding of the way the left ventricle ejects blood into the aorta has
      been advanced by considering aortic flow in terms of the elemental haemodynamic
      forces, compression and expansion wavefronts. The pattern of aortic wave
      intensity indicates that the contracting and relaxing left ventricle generates
      compression and expansion waves and that it is these, rather than the waves
      reflected from the arteries, that dominate ejection in the normal cardiovascular
      system. The wave intensity is a novel haemodynamic variable, with the potential
      to provide information about heart-vessel coupling and the fluid dynamic
      consequences for cardiac output of myocardial contraction and relaxation. This
      information should now be realised in experimental studies of the integrated
      circulation in health and in disease.

PMID- 8287393
TI  - The reasons why clinical cardiologists disregard reperfusion arrhythmias.

PMID- 8287394
TI  - The reasons why basic scientists study reperfusion arrhythmias.

PMID- 8287395
TI  - Acute myocardial infarction in dogs with experimental diabetes.
AB  - OBJECTIVE: The aim was to examine whether diabetes interferes with the
      development of myocardial injury in a canine ischaemia-reperfusion model.
      METHODS: Non-insulin-requiring diabetes was induced in dogs by the streptozotocin
      alloxan method. After 75 d, the dogs were anaesthetised and myocardial infarction
      was provoked by occluding the left anterior descending coronary artery for 2 h
      followed by 6 h reperfusion. RESULTS: Diabetic dogs had higher blood glucose
      [9.4(SEM 1) mmol.litre-1], fructosamine [417(57) mumol.litre-1], and glycated
      haemoglobin [3.3(0.7)%], than control dogs [5.5(0.6), p = 0.04, 243(15), p =
      0.01, and 0.7(0.2), p = 0.003, respectively], and they also had higher serum
      lipids (p = 0.001) and platelet aggregation (p = 0.03). Area at risk was similar
      in diabetic and control dogs but in contrast to controls (r = 0.78, p = 0.007),
      area at risk and infarct size were not correlated in diabetics (r = 0.08). In
      both groups, collateral flow was the major determinant of infarct size: r = -0.73
      in controls (p = 0.02) and -0.97 in diabetics (p = 0.001). In spite of higher
      subendocardial collateral flow in diabetics [representing 21.6(6)% of the flow in
      the corresponding non-ischaemic zone] than in controls [11.2(6)%], infarct size
      was similar in both groups. However, the mean observed infarct size in the
      diabetic group [7.5(2.8)% of the left ventricle] was significantly (p < 0.03)
      larger than the mean predicted infarct size [5.2(2)%]. Multivariate analysis
      confirmed that diabetes, as well as collateral flow, is an independent (p = 0.03)
      predictor of infarct size. CONCLUSIONS: For a given collateral flow, diabetic
      dogs develop larger infarcts than controls. Further studies are required to
      investigate the biochemical mechanism(s) underlying this deleterious effect.
      However, this may partly explain the poor prognosis of myocardial infarction in
      diabetic persons.

PMID- 8287396
TI  - Acute myocardial infarction and diabetes mellitus.

PMID- 8287397
TI  - Collagen induced human platelet aggregation: serotonin receptor antagonism
      retards aggregate growth in vitro.
AB  - OBJECTIVE: The role of platelet derived serotonin (5-HT) in collagen induced
      human platelet aggregation was examined both in hirudinised plasma and whole
      blood. Hirudin was used to maintain normocalcaemia, thereby avoiding erroneous
      findings often obtained with citrated blood. METHODS: Platelet aggregation,
      aggregate growth, and primary platelet aggregation were quantified by optical
      aggregometry and platelet counting respectively. RESULTS: In plasma, platelet
      aggregation induced by 5-HT (3 microM) in the presence of adrenaline (1 microM)
      was inhibited by more than 85% by ICI 170809 (3 microM, IC50 0.1 microM), a
      specific platelet 5-HT2 antagonist. With collagen (0.5 micrograms.ml-1), ICI
      170809 retarded the rate of aggregation by 30%, whereas aspirin abolished the
      response. In contrast, ICI 170809 inhibited collagen induced primary aggregation
      by less than 10% in both plasma and whole blood. CONCLUSIONS: (1) 5-HT
      contributes to collagen induced aggregate growth and 5-HT2 receptor antagonism
      with ICI 170809 retards the rate of growth. (2) This could explain the efficacy
      of 5-HT2 antagonists in limiting coronary thrombosis despite the limited role of
      5-HT in primary aggregation.

PMID- 8287398
TI  - Mechanisms causing coronary microvascular dysfunction following crystalloid
      cardioplegia and reperfusion.
AB  - OBJECTIVE: The aim was to examine the mechanisms of coronary microvascular
      dysfunction during cardiopulmonary bypass and ischaemic arrest using a
      crystalloid cardioplegic solution. METHODS: Porcine hearts were arrested with
      cold hyperkalaemic (K+ = 25 mmol.litre-1) cardioplegic solution for 1 h during
      cardiopulmonary bypass and then reperfused for 1 h. Selected hearts were arrested
      but not reperfused. Coronary vessels of non-instrumented pigs were used as
      controls. In vitro vascular responses of subepicardial and subendocardial
      arterioles were examined in a pressurised (40 mm Hg) no flow state with video
      microscopy. RESULTS: Following 1 h of ischaemic cardioplegia, endothelium
      dependent relaxations of epicardial arterioles to the receptor mediated agent ADP
      and the non-receptor-mediated agent calcium ionophore A23187 were moderately
      reduced, and the contractile responses to KCl or the thromboxane A2 analogue
      U46619 were reduced compared to responses of vessels from control animals. After
      1 h of reperfusion, U46619 caused contraction greater than control values, while
      contraction to KCl and endothelium dependent relaxations to ADP or A23187 were
      further reduced. Responses of endocardial microvessels to serotonin were slightly
      more affected by cardioplegia and reperfusion than were epicardial vessels, while
      the effect on responses of epicardial and endocardial vessels to bradykinin or
      A23187 were similar. Endothelium independent relaxation to sodium nitroprusside
      was not altered in any of the experimental groups. The addition of manganese
      superoxide dismutase to the cardioplegic solution markedly preserved endothelium
      dependent responses to ADP and A23187 and contractile response to U46619,
      compared to the responses of vessels from the plain crystalloid cardioplegia
      group, but had no effect on relaxation to sodium nitroprusside or on contraction
      to KCl. Five hours of normokalaemic hypothermia (5-10 degrees C) in Krebs buffer
      had minimal effect on vasodilator responses. Electron microscopy revealed
      preserved endothelial and smooth muscle cell structure, and focal mononuclear
      leucocyte-endothelium adherence following cardioplegic arrest and reperfusion.
      CONCLUSIONS: Ischaemic cardioplegia-reperfusion induced endothelium dependent and
      direct smooth muscle microvascular dysfunction is at least partially mediated by
      prolonged exposure of vessels to hyperkalaemia and to the generation of oxygen
      derived free radicals. Leucocytes probably mediate injury during reperfusion,
      while hypothermia has minimal effect on recovery of vasomotor function.

PMID- 8287399
TI  - Selective and time related activation of the cardiac renin-angiotensin system
      after experimental heart failure: relation to ventricular function and
      morphology.
AB  - OBJECTIVE: The cardiac renin-angiotensin system is activated in experimental
      heart failure, but it is unknown at what stage of heart failure it becomes
      activated, and whether activation is related to ventricular dysfunction and
      dilatation. Changes in activity of cardiac, renal, and plasma angiotensin
      converting enzyme (ACE) were therefore examined at different stages of
      experimental heart failure, with simultaneous measurements of left ventricular
      pressure, systolic dP/dt, and inner ventricular radius. METHODS: Heart failure
      was induced by experimental infarction in 17 normotensive male Wistar rats; 14
      rats were sham operated. Rats were killed 3, 5, or 80 d after infarction. In an
      isolated heart perfusion, left ventricular pressure and systolic dP/dT were
      measured. ACE activity was determined in samples of the left and right cardiac
      ventricle, kidney, and plasma. Radius of the ventricular cavity was
      planimetrically determined in transverse sections of the left ventricle. RESULTS:
      At the different stages both left ventricular pressure and systolic dP/dT
      progressively decreased and inner radius of the left ventricle increased in all
      heart failure groups. ACE activity in the left ventricle increased significantly
      in all heart failure groups and correlated inversely with left ventricular
      pressure (R = -0.81; p < 0.001) and dP/dt (R = -0.85; p < 0.001). ACE activity in
      the kidney was only increased 80 d after the induction of heart failure [17(SEM
      1) v 11.2(0.5) nM His-Leu generated per min.mg-1, p < 0.01], while plasma ACE
      activity was not increased in any heart failure group. CONCLUSIONS: Cardiac ACE
      is activated in the early stage after induction of heart failure and is related
      to the amount of dysfunction. ACE in the kidney is activated only in the chronic
      stage. The cardiac renin-angiotensin system therefore already appears to be an
      important neurohumoral adjustment in the early stage of heart failure and is
      thereby a suitable target for early intervention by ACE inhibitors.

PMID- 8287400
TI  - Endothelium independent relaxation of human coronary arteries by 17 beta
      oestradiol in vitro.
AB  - OBJECTIVE: There is accumulating evidence that oestrogen replacement therapy
      protects against the development of coronary atherosclerosis and myocardial
      infarction in postmenopausal women. The mechanism of this protective effect is
      uncertain. The aim of this study was to measure the effects of 17 beta-oestradiol
      on human epicardial coronary artery tone. METHODS: Coronary artery rings were
      obtained from explanted hearts during cardiac transplantation. The rings were
      suspended in organ baths for isometric tension measurements. The rings were
      precontracted with prostaglandin F2 alpha, and were then exposed to either 17
      beta-oestradiol (0.3 nM-3 microM) or solvent control (0.2% ethanol v/v). In some
      rings, cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'
      monophosphate content were measured by radioimmunoassay. RESULTS: 17 beta
      Oestradiol induced a significant relaxation [maximum effect: 84(SD 18)%]. The
      onset of the relaxant effect occurred within 5 min, and was maximal within 40
      min. The relaxation in response to 3 microM 17 beta-oestradiol was of similar
      magnitude in rings with and without intact endothelium. The maximum relaxation
      induced by 3 microM 17 beta-oestradiol was greater in arteries from hearts
      obtained from women than in those obtained from men [-100.0(3.0)% v -77.5(17.6)%,
      respectively]. The exposure of rings to 3 microM 17 beta-oestradiol for 30 min
      resulted in a significant increase in both cyclic AMP and cyclic GMP content, by
      88% and 182%, respectively. CONCLUSIONS: 17 beta-Oestradiol produced an
      endothelium independent relaxation of precontracted human coronary arteries in
      vitro, and this effect was associated with an increase in both cyclic AMP and the
      cyclic GMP content. This direct relaxant effect of oestrogens on coronary
      arteries may contribute to the beneficial effects of oestrogen replacement
      therapy in postmenopausal women.

PMID- 8287401
TI  - Transadventitial localisation of atheromatous plaques by fluorescence emission
      spectrum analysis of mono-L-aspartyl chlorin e6.
AB  - OBJECTIVE: The aim was to demonstrate specific detection of the fluorescence
      spectra of mono-L-aspartyl chlorin e6 (NPe6) emitted from atherosclerotic
      arterial lesions using an extravascular approach. METHODS: Cholesterol fed
      atherosclerotic rabbits were injected intravenously with 0.5 mg.kg-1 of NPe6. A
      fluorescence spectrum analysis system with a dual real time imaging system and a
      flexible endoscopic catheter was used. The pulsed excimer dye laser excited the
      photosensitiser. The fluorescence spectra were measured by a fluorescence
      spectrophotometer. RESULTS: Analysis of fluorescence spectra detected from
      outside the adventitia showed that a fluorescence spectrum peak at 675 nm was
      obtained only in parts of the artery with an atheromatous plaque; however, no
      fluorescence could be shown in aortic segments free of atheroma. It was also
      noted that the intensity of the specific peak of the spectrum detected from
      outside a vessel was closely related to the depth of atheromatous lesions, as
      determined by histological analysis. An in vivo study revealed good correlation
      between the peak intensity (which could vary with the amount of NPe6 accumulated
      in the tissue) measured laparoscopically from outside the abdominal aorta and the
      peak intensity measured angioscopically from inside the abdominal aorta.
      CONCLUSIONS: It is possible to detect atheroma from outside a vessel by
      fluorescence spectrum analysis employing NPe6 as the probe.

PMID- 8287402
TI  - Protein phosphorylation and cardiac function: cholinergic-adrenergic interaction.
AB  - OBJECTIVE: The muscarinic inhibition of cyclic AMP (cAMP) mediated contractile
      effects may not only be the result of a reduction in cAMP levels, but may also
      involve cAMP linked protein phosphorylation in the heart. To show that a
      cholinergic agonist may antagonise the effects of agents that induce the cAMP
      signalling sequence at the level of protein phosphorylation, the effect of
      carbachol was investigated on the in vivo phosphorylation of phospholamban,
      troponin I, and a 15 kDa protein during positive inotropic intervention with
      isoprenaline, forskolin, and a phosphodiesterase inhibitor in the isolated rat
      heart. METHODS: The contractile activity of the heart was monitored during drug
      administration, and the hearts were freeze clamped for assay of protein
      phosphorylation and metabolites [cAMP, cyclic guanosine monophosphase (cGMP),
      cAMP dependent protein kinase (cA-PK), and phosphorylase a]. For estimation of
      the amount of in vivo phosphorylation, a "back phosphorylation" method was used.
      RESULTS: Carbachol attenuated in vivo phosphorylation, induced by cAMP increasing
      drugs, of all the phosphoproteins studied, whereas the accumulation of cAMP was
      not affected or was decreased to 61% after exposure to isoprenaline alone. In
      addition, the cAMP mediated phosphorylase a activation was completely reversed by
      carbachol. similarly, sodium nitroprusside reduced phosphorylation as well as the
      contractile force of the investigated phosphoproteins. CONCLUSIONS: These data
      confirm the reduction of cAMP mediated cardiac protein phosphorylation by
      carbachol. The cholinergic antagonism may primarily involve cellular target
      systems distal to sites of cAMP generation. The observed similarity in the
      cardiac response to carbachol and sodium nitroprusside indicates a role of cGMP
      in the antiadrenergic action of carbachol in the myocardium.

PMID- 8287403
TI  - Dispersion of refractoriness in normal and ischaemic canine ventricle: effects of
      sympathetic stimulation.
AB  - OBJECTIVE: Dispersion in refractoriness is considered a major factor in induction
      and persistence of cardiac arrhythmias. The sympathetic nervous system is known
      to modulate refractoriness. An index of refractoriness has therefore been
      assessed in normal and ischaemic myocardium simultaneously at multiple sites,
      with and without sympathetic stimulation. METHODS: In six dogs on total
      cardiopulmonary bypass the average interval between local activations was
      measured during artificially induced ventricular fibrillation from extracellular
      electrograms simultaneously recorded from 32 ventricular sites. These local
      ventricular fibrillation intervals may be used as an index of local
      refractoriness. RESULTS: During regional ischaemia, ventricular fibrillation
      intervals of ischaemic sites could prolong by up to 60% after 3 min following
      coronary occlusion. Left stellate ganglion stimulation during ischaemia produced
      either no response or prolonged the ventricular fibrillation intervals even
      further at ischaemic sites, whereas ventricular fibrillation intervals at non
      ischaemic sites shortened. Dispersion in refractoriness across the ischaemic
      border increased by 14-59% in individual hearts following sympathetic stimulation
      during acute, regional ischaemia. CONCLUSIONS: Due to opposite effects on normal
      and ischaemic myocardium, sympathetic stimulation increases the difference in
      refractoriness over the ischaemic border. This may enhance the chance for
      regional conduction block and the propensity to re-entrant arrhythmias.

PMID- 8287404
TI  - Surgical preparation induces injury and promotes smooth muscle cell proliferation
      in a culture of human saphenous vein.
AB  - OBJECTIVE: The aim was to investigate the influence of vessel wall injury,
      incurred during routine vein preparation, on smooth muscle cell proliferation.
      METHODS: A newly developed quantitative organ culture was used, in which segments
      of human saphenous vein were cultured in medium containing 30% fetal bovine serum
      and 1 microCi.ml-1 of [3H]thymidine for up to 14 d. Endothelial integrity was
      measured by scanning electron microscopy and medial cell viability by adenine
      nucleotide concentrations. Cell proliferation was measured by DNA concentration,
      global incorporation of [3H]thymidine, and by counting labelled cells in
      autoradiographs of transverse sections. RESULTS: Surgical preparation led to
      endothelial injury and reduced adenine triphosphate concentration by 60%.
      Surgically prepared veins also suffered a significant decline in DNA
      concentration during culture, which implied that injury led to cell necrosis.
      Surgically prepared veins showed 2.1- and 2.7-fold greater global incorporation
      of [3H]thymidine than freshly isolated veins after 7 and 14 d in culture,
      respectively, which corresponded with a 23-fold and 11-fold greater abundance of
      thymidine labelled cells in the medial layer. Intimal thickening and the numbers
      of total and thymidine labelled cells in the intimal layer were similar.
      CONCLUSIONS: The data show that injury incurred during routine surgical
      preparation is associated with enhanced medial smooth muscle cell proliferation.
      The effect of injury was most probably to permit an increased response of medial
      smooth muscle cells to serum derived mitogens.

PMID- 8287405
TI  - Age associated changes in membrane currents in rat ventricular myocytes.
AB  - OBJECTIVE: Action potential duration of senescent rat ventricular myocytes is
      longer than in young adults. The aim of the study was to determine whether age
      related changes in L-type calcium current (ICa), transient outward potassium
      current (ITO), and inwardly rectifying potassium current (IK1) are involved in
      the prolongation of the early (ICa, ITO) and late (IK1) portions of the rat
      action potential plateau. METHODS: Whole cell voltage clamp techniques were used
      to study these currents in ventricular myocytes isolated from young (2-3 months),
      middle aged (8-9 months), and senescent (24-25 months) rats. RESULTS: There were
      no differences in the magnitude of ICa among age groups once currents were
      normalised for capacitative surface area. The voltage dependence of ICa
      activation and steady state inactivation in the three age groups was also
      similar. At test potentials of 0 and +10 mV, there was a significant (p < or =
      0.05) slowing in the time course of inactivation of ICa; the time constants of
      inactivation increased with age [young v old in ms(SEM): 0 mV, 22.2(2.2) v
      38.0(5.0) (slow); +10 mV, 8.0(2.0) v 15.6(2.0) (fast)]. With internal EGTA to
      buffer intracellular Ca2+, no significant age related differences in action
      potential duration or the time course of ICa inactivation were observed. There
      was an age associated decrease in peak ITO density in the old (n = 25) compared
      to the young (n = 25) cell group (p < 0.05). The only age associated change in
      the kinetic properties of ITO was a small but consistent slowing in the time
      constants of inactivation at most test voltages measured, with significance
      occurring at 0 mV in the slow (tau 2) component. CONCLUSIONS: ICa density is
      maintained in senescence; ICa inactivation, however, is slowed. Age related
      differences in action potential duration and ICa inactivation were reduced by
      buffering intracellular Ca2+. ITO channels appear to retain normal function
      through the aging process but overall there is a reduced channel density. The age
      associated changes in these currents should contribute to prolongation of action
      potential duration of the early plateau phase seen in the senescent rat.

PMID- 8287406
TI  - Effect of age on phosphorylated compounds and mechanical activity of isolated rat
      heart: a 31P-NMR study.
AB  - OBJECTIVE: The aim was to test the hypothesis that aging may change the function
      and energetics of isolated hearts subjected to an increased work load induced by
      varying the calcium concentration ([Ca2+]) in the perfusion fluid from 0.5 to
      1.0, 1.5, or 2.0 mM. METHODS: Female Wistar rats aged 4, 12-14, and 22-24 months
      were used. Their hearts were perfused through the aorta and changes in myocardial
      phosphorylated compound concentration were measured by means of 31P-nuclear
      magnetic resonance spectroscopy and biochemical analysis. Myocardial
      contractility was measured in situ in closed heart anaesthetised animals and was
      followed in vitro during perfusion. RESULTS: The contractile indices measured in
      situ revealed a decrease with aging of the left ventricular developed pressure
      and dP/dtmax, while heart rate did not show any significant difference. In all
      age groups the stepwise increase in [Ca2+] caused a graded increase in left
      ventricular pressure in the perfused hearts. In aged rats, the left ventricular
      pressure associated with the different concentrations of Ca2+ was significantly
      lower than in young rats. In all three groups the myocardial content of inorganic
      phosphorus (Pi) increased in response to a rise in [Ca2+] and left ventricular
      pressure. The ATP content of the hearts remained constant in all three groups at
      each value of [Ca2+] induced left ventricular pressure. However, both ATP and
      total adenine nucleotide contents of the hearts were lower in aged rats. When the
      alteration in Pi due to each increase in [Ca2+] was expressed in relation to the
      rise in left ventricular developed pressure, this relationship was not
      significantly different in the three groups of hearts. CONCLUSIONS: The reduced
      mechanical activity of aged rat hearts is not due to a diminished efficiency of
      the mechanisms transferring high energy phosphates.

PMID- 8287408
TI  - Effects of diacetyl monoxime on the electrical properties of sheep and guinea pig
      ventricular muscle.
AB  - OBJECTIVE: Diacetyl monoxime (DAM), a nucleophilic agent with "phosphatase-like"
      activity, has been found to effectively and reversibly block cardiac muscle
      contraction, while the cells remain capable of generating transmembrane action
      potentials. The aim of this study was to characterise the effects of DAM on the
      electrical properties of cardiac muscle. METHODS: Sheep epicardial muscle, guinea
      pig papillary muscle, and guinea pig ventricular myocytes were studied using
      conventional microelectrode techniques as well as single electrode current and
      voltage clamp techniques. RESULTS: DAM (5-20 mM) decreased action potential
      duration at 50% and 90% repolarisation levels (APD50, APD90) and refractory
      period in a dose dependent manner without causing significant changes in action
      potential amplitude, maximum upstroke velocity, or resting membrane potential.
      DAM induced a slight decrease in action potential conduction velocity in both the
      longitudinal and transverse directions, but on average the conduction velocity
      recorded in the presence of the drug was not significantly different from
      control. The time course of the APD restitution curve was not significantly
      changed but the frequency dependent APD variations were reduced. The ionic bases
      for these changes were studied in guinea pig ventricular myocytes. As with the
      results obtained in tissue preparations, DAM 15 mM decreased APD50 and APD90 by
      35% and 29%, respectively. Under voltage clamp conditions, DAM led to a 35%
      reduction of ICa. The delayed rectifier IK current and the inward rectifier
      background current were also partially depressed by DAM but to a lesser extent.
      All of these effects were reversible upon washout. CONCLUSIONS: Aside from its
      well known effect as an electromechanical uncoupler, DAM causes a small,
      reversible, and non-selective reduction of several membrane conductances.
      Provided such effects are taken into consideration, DAM is a valuable tool in
      electrophysiological studies.

PMID- 8287407
TI  - Impaired posthypoxic relaxation in single cardiac myocytes: role of intracellular
      pH and inorganic phosphate.
AB  - OBJECTIVE: The aim was to examine the effects of alterations in intracellular pH
      and inorganic phosphate concentration (known to influence myofilament kinetics
      and to change rapidly during hypoxia) on cell contraction, relaxation, and the
      Ca2+ transient in normoxic and hypoxic myocytes. METHODS: Single adult rat
      ventricular myocytes were electrically stimulated (0.2 Hz) and cell length
      (photodiode array), intracellular Ca2+ (indo-1 fluorescence), or intracellular pH
      (SNARF-1 fluorescence) measured. Hypoxia was induced in a special open chamber in
      which a laminar layer of argon prevented the back diffusion of atmospheric
      oxygen. RESULTS: Electrically stimulated contraction was preserved during
      exposure to hypoxia. At reoxygenation 10 minutes later the time from the stimulus
      to the peak of contraction (TPK) increased by 30(SEM 9)% and the time from the
      peak of contraction to 50% recovery of cell length (RT50) increased by 59(13)%
      relative to prehypoxic values (n = 8). These changes were not accompanied by a
      change in the kinetics of the Ca2+ transient. pHi fell from a baseline of
      7.33(0.04) to 7.25(0.03) during hypoxia and then overshot to 7.44(0.03) at
      reoxygenation (n = 5). Since an intracellular alkalosis can slow myofilament
      relaxation, proton extrusion routes were blocked to examine posthypoxic
      relaxation in the absence of an alkalosis. Despite inhibition of the pHi
      overshoot, posthypoxic relaxation remained impaired. Intracellular inorganic
      phosphate levels were manipulated in two protocols (2-deoxyglucose to "trap"
      phosphate and Tris(hydroxymethyl)-aminomethane to buffer phosphate) and both TPK
      and RT50 increased in normoxic cells. Having established that these two
      interventions, which would be expected to decrease intracellular inorganic
      phosphate, result in a slowing of relaxation, myocytes were first phosphate
      loaded (exposed to 5.0 mM phosphate) and then made hypoxic and reoxygenated after
      10 min to blunt the expected fall in phosphate accompanying reoxygenation. This
      led to a reduction in the slowing of contraction and relaxation following
      reoxygenation [TPK increased by 7(5)% and RT50 by 17(9)%, n = 8; p < 0.05 v cells
      studied in control buffer]. CONCLUSIONS: Impaired posthypoxic relaxation is not
      the result of changes in pHi but is attenuated by phosphate loading of cells and
      may be due to a rapid decrease in intracellular phosphate accompanying the
      resynthesis of high energy phosphates at reoxygenation.

PMID- 8287409
TI  - Effect of pressure and volume overload on proto-oncogene expression in the
      isolated working rat heart.
AB  - OBJECTIVE: The aim was to study the effect of pressure and volume overload on the
      expression of the proto-oncogenes, c-fos and c-myc, in isolated perfused working
      rat hearts and to compare these results with the known effects of noradrenaline.
      METHODS: Working rat hearts were obtained by converting the Langendorff
      preparation into the working mode by perfusion through the left atrium. Using
      specific cDNA clones, the mRNAs of c-fos and c-myc were measured by northern
      blots and quantified with densitometry. Total RNA was isolated from hearts after
      stimulation with noradrenaline (3 x 10(-8) M), after increasing afterload from 80
      to 100 cm H2O, and left atrial filling pressure (preload) from 8 to 16 cm H2O for
      15, 30, 60, 90, and 120 min, respectively. RESULTS: The mRNAs of c-fos and c-myc
      were not detectable in freshly excised rat hearts. When the hearts were perfused
      in the working mode for 15, 30, 60, 90, and 120 min, c-fos and c-myc mRNAs were
      measurable, and these mRNA levels served as control baseline values that were set
      at 100%. When noradrenaline was infused, c-fos mRNA was increased fivefold after
      30, threefold after 60, and 3.8-fold after 90 min. The mRNA of c-myc was
      increased 1.8-fold after 60 min and 3.8-fold after 90 min. The increase in
      afterload induced a threefold increase of c-fos mRNA after 30 min and a threefold
      increase of c-myc mRNA after 90 min. When preload was increased, c-fos mRNA rose
      1.8-fold after 30 min, and c-myc mRNA twofold after 60 min and 2.8-fold after 90
      min compared to the controls. CONCLUSIONS: Pressure and volume overload have
      effects on the expression of c-fos and c-myc mRNA that are similar to those
      obtained with noradrenaline stimulation which induced the most pronounced
      signals. Our time course studies showed that c-fos mRNA always rose before c-myc
      mRNA. This common sequential induction pattern may have important signal function
      in the processes that trigger the development of cardiac hypertrophy.

PMID- 8287410
TI  - Remodelling and functional alterations of the rabbit coronary artery in volume
      overloaded heart.
AB  - OBJECTIVE: The aim was to study the contractility of the conduit coronary artery
      to vasoactive agents in developing and established volume overload cardiac
      hypertrophy and to compare it with structural alterations in the artery. METHODS:
      Aortic valve insufficiency in rabbits was used to produce a volume overloaded
      heart. One month (developing hypertrophy), and four months (stabilised
      hypertrophy) after inducing aortic insufficiency, the isometric contraction of
      the coronary artery to acetylcholine, serotonin, and potassium chloride was
      recorded. For transmission electron microscopy, the coronary arteries were
      perfused via the ascending aorta with glutaraldehyde fixative under constant
      pressure. The point counting method was used for quantitative evaluation.
      Semithin sections were used to determine the geometry (ie, the inner diameter and
      wall thickness) of the coronary artery by light microscopy. RESULTS: A
      significant increase in heart weight and heart weight to body weight ratio was
      found after one month and four months of volume overload. Concentration-response
      relations of the coronary artery to all three agents were shifted to the right;
      in developing hypertrophy the shift was non-significant, in stabilised
      hypertrophy it was significant. The contractions were weakened by up to one fifth
      of the control values. An associated increase in wall thickness of the coronary
      artery was found, due to a significant expansion of the intercellular space. The
      internal diameter did not change significantly. Ultrastructural findings (an
      increase of the area occupied by organelles in myocytes) suggested a transition
      from "contractile" to more "synthetic" type of smooth muscle cells. CONCLUSIONS:
      In cardiac hypertrophy due to volume overload, the structure of the coronary
      arteries reflects the long term haemodynamic alterations, particularly through an
      increase in the non-cellular component. In parallel, the contraction efficiency
      to vasoactive drugs decreases markedly.

PMID- 8287411
TI  - Mechanisms of noradrenaline release in the anoxic heart of the rat.
AB  - OBJECTIVE: The aim was to examine the time course of exocytotic and "spontaneous"
      noradrenaline overflow and the influence of an Uptake1 inhibitor, desipramine, in
      rat hearts subjected to anoxic and substrate-free perfusion. METHODS: Hearts were
      perfused with a constant flow and exocytotic noradrenaline overflow was elicited
      either by electrical stimulation of the left stellate ganglion or by K+
      depolarisation. Noradrenaline overflow was measured by HPLC. RESULTS: Energy
      depletion for a period of 30 min resulted in an enhanced spontaneous
      noradrenaline overflow and a progressive decline in the nerve stimulation induced
      noradrenaline overflow. However, noradrenaline overflow induced by 40 mM K+ was
      enhanced by three- to fourfold in the energy depleted conditions. During anoxia,
      desipramine (0.3 microM) inhibited the spontaneous noradrenaline overflow and
      partly increased, in the early phase of anoxia, noradrenaline overflow by nerve
      stimulation, but showed no effect on K+ induced overflow. Further experiments
      showed that K+ at 10 mM failed to evoke noradrenaline overflow in normoxic hearts
      but induced a significant overflow in energy depleted hearts, either in the
      presence or absence of desipramine; quantities of noradrenaline overflow in
      response to 10-40 mM K+ were substantially higher in anoxia. This difference in
      noradrenaline overflow caused by K+ during normoxia and anoxia was partly
      narrowed by desipramine which enhanced overflow in normoxia. CONCLUSIONS:
      "Spontaneous" and exocytotic noradrenaline release coexist within the 30 min
      period of anoxia but their responses to Uptake1 inhibitor differ. K(+)-induced
      noradrenaline overflow was markedly augmented by energy depletion due to a
      combination of failed neuronal reuptake and enhanced exocytosis.

PMID- 8287412
TI  - Ischaemic preconditioning is not mediated by oxygen derived free radicals in
      rats.
AB  - OBJECTIVE: Although several studies have shown that ischaemic preconditioning
      greatly limits myocardial infarct size in the rat, the mechanisms of the
      beneficial effect of preconditioning in this species are not known. Experiments
      in dogs and rabbits have suggested that this effect could be related in part to
      the production of oxygen derived free radicals, as free radical scavengers
      partially prevent the limitation of infarct size induced by preconditioning. This
      study was designed to assess the contribution of oxygen derived free radicals in
      the infarct size limiting effects of preconditioning in rats, using the cell
      diffusible free radical scavenger N-2-mercaptopropionyl glycine (MPG). METHODS:
      Open chest rats underwent 20 minutes of coronary occlusion followed by one hour
      of reperfusion. Preconditioning was elicited by three cycles of five minutes
      ischaemia and five minutes reperfusion. MPG (20 mg.kg-1) was infused for 60
      minutes starting 30 minutes before preconditioning. Control hearts (with or
      without MPG) were treated identically but without ischaemic preconditioning. Area
      at risk and infarct size were determined by India ink injection and
      triphenyltetrazolium chloride stain, with computerised analysis of enlarged
      sections after colour video acquisition. RESULTS: During preconditioning,
      reperfusion after the first episode of ischaemia was associated with a high
      occurrence of severe ventricular arrhythmias, and this was reduced by MPG.
      Preconditioning, however, reduced arrhythmias and mortality during subsequent
      episodes of ischaemia and reperfusion. In the absence of MPG, preconditioning
      greatly limited infarct size (from (mean (SEM)) 59.8(3.9)% to 1.2(0.6)% of the
      area at risk; p < 0.01). MPG alone did not affect infarct size (60.5(6.1)%), and
      did not modify the infarct size limiting effect of preconditioning (infarct size:
      preconditioning 1.2(0.6)%; preconditioning + MPG 2.9(1.2)%. CONCLUSIONS:
      Preconditioning greatly reduced infarct size, and this was not affected by MPG.
      These experiments suggest that production of oxygen derived free radicals does
      not contribute to preconditioning in the rat heart.

PMID- 8287413
TI  - Central dopaminergic origin of bromocriptine induced tachycardia in normotensive
      rats.
AB  - OBJECTIVES: This study was undertaken to investigate the mechanism of the
      tachycardic effect of bromocriptine, a specific dopamine D-2 receptor agonist,
      which is not abolished, as previously reported, by intravenous domperidone, a
      selective dopamine D-2 antagonist unable to cross the blood brain barrier. Two
      hypotheses were tested: (1) that the increase in heart rate after intravenous
      treatment with bromocriptine could be related to central dopamine receptor
      stimulation and (2) that it could be induced by a release of adrenaline from the
      adrenal medulla. METHODS: Changes in mean aortic pressure and heart rate, induced
      by treatment with 150 micrograms.kg-1 bromocriptine intravenously, were measured
      in conscious or anaesthetised normal or adrenalectomised rats submitted to
      various pretreatments. RESULTS: In conscious intact rats, intravenous
      bromocriptine decreased mean aortic pressure (-11 (SEM1) mm Hg) and increased
      heart rate (62(12)) beats.min-1). Both effects were prevented by intravenous
      pretreatment (0.3 mg.kg-1) with dopamine D-2 receptor antagonists able to cross
      the blood brain barrier, such as haloperidol, sulpiride, and metoclopramide. In
      anaesthetised rats, domperidone (50 and 20 micrograms.kg-1) given via a lateral
      cerebral ventricle abolished the bromocriptine induced tachycardia without
      affecting the hypotensive response. Both effects were unchanged after bilateral
      adrenalectomy but were completely abolished by intravenous haloperidol
      pretreatment (0.3 mg.kg-1) in conscious adrenalectomised rats. CONCLUSIONS: These
      results suggest that in anaesthetised and conscious normotensive rats, the
      bromocriptine induced tachycardia is not related to a release of adrenaline from
      the adrenal medulla but could be elicited by central dopamine D-2 receptor
      stimulation through a possible increase in cardiac sympathetic tone.

PMID- 8287414
TI  - Intracoronary papaverine but not adenosine reduces regional ventricular function.
AB  - OBJECTIVES: Whether intracoronary papaverine or adenosine leads to reductions in
      regional left ventricular function was tested. METHODS: Fifteen anaesthetised
      dogs were prepared to record aortic pressure, left ventricular pressure dP/dt,
      electrocardiogram, regional ventricular shortening, and phasic and mean left
      circumflex coronary blood flow, and to give intracoronary boluses of papaverine
      (2, 4, or 6 mg) or adenosine (0.37 and 1.87 mg). RESULTS: Injected doses were
      chosen to mimic those given in the clinical setting. Papaverine (6 mg) reduced
      aortic pressure (mean 96(SD 17) to 89(18) mm Hg; p < 0.05), segmental shortening
      of the infused left circumflex zone (12(5) to 7(9)%; p < 0.05), and area of the
      pressure-length loop of the infused zone (120(71) to 53(47) mm.mm Hg; p < 0.05).
      Papaverine increased coronary blood flow (48(25) to 259(95) ml.min-1; p < 0.05),
      coronary vascular conductance (0.40(0.20) to 2.93(0.94) ml.mm Hg-1.min-1; p <
      0.05), heart rate (88(27) to 100(28) beats.min-1; p < 0.05), and the segmental
      shortening (17(6) to 19(3)% p < 0.05) and area of the pressure-length loop
      (130(32) to 177(33) mm.mm Hg; p < 0.05) of the non-infused left anterior
      descending region. The hyperaemia elicited by papaverine was greater than that of
      reactive hyperaemia (p = 0.008). Papaverine also increased the QT interval
      corrected for heart rate (0.35(0.04) to 0.45(0.05) s; p < 0.05). When adenosine
      was given, coronary blood flow and coronary vascular conductance were increased
      to similar degrees as those during reactive hyperaemia (41(12) to 210(75) ml.min
      1 and 0.46(0.14) to 2.43(0.83) mm Hg.ml-1.min-1, respectively; NS). No effects on
      segmental shortening or the area of the pressure-length loop in either zone were
      found. Also, adenosine had no effect on the QT interval. CONCLUSIONS: These
      adverse effects of intracoronary papaverine have important implications in its
      use in patients, particularly in those in whom abnormal cardiac function already
      exists. Adenosine, on the other hand, seems to be without deleterious effects.

PMID- 8287415
TI  - Enhanced gene expression of calcium regulatory proteins in stunned porcine
      myocardium.
AB  - OBJECTIVE: Increasing evidence points to a molecular disturbance of Ca2+
      homeostasis in stunned myocardium. The aim of this study was therefore to
      investigate the expression of mRNAs for Ca2+ binding proteins related to the
      sarcoplasmic reticulum in a porcine model of myocardial stunning. METHODS: In 22
      anaesthetised pigs, stunning was achieved by one or two cycles of 10 min left
      anterior descending coronary artery occlusion and reperfusion. Hearts were
      excised at various timepoints of the protocol. Total RNA was extracted from
      stunned (experimental) as well as normally perfused (control) myocardium.
      RESULTS: Northern blot analysis using radioactive cDNA probes revealed that the
      Ca(2+)-ATPase mRNA levels increased 1.6-fold compared to the control value at 90
      min of the second reperfusion. The steady state level of phospholamban mRNA rose
      2.5-fold at 180 min of reperfusion. A 2.3-fold increase in calsequestrin mRNAs
      was observed after 90 min of the second reperfusion. The calmodulin and alpha,
      beta myosin heavy chain mRNA levels were unchanged. A glyceraldehyde-3-phosphate
      dehydrogenase cDNA probe served as a reference system. Nuclear run-on assays
      showed increased transcription for Ca(2+)-ATPase and calsequestrin at 90 min of
      reperfusion, supporting the view that increased mRNA levels seen with northern
      hybridisation were due to increased transcription of the respective gene.
      CONCLUSIONS: The results suggest specific repair mechanisms of stunned myocardium
      and point to the involvement of calcium regulatory proteins related to the
      sarcoplasmic reticulum in the pathogenesis of myocardial stunning.

PMID- 8287416
TI  - Myocardial adaptation during acute hibernation: mechanisms of phosphocreatine
      recovery.
AB  - OBJECTIVES: Acute hibernation, defined as a prolonged period of moderately
      reduced oxygen supply and stable haemodynamic function, results in metabolic
      adaptation characterised primarily by an increase in phosphocreatine. The
      mechanism of this increase in phosphocreatine is unknown, but has been postulated
      to result from either an increase in adenosine triphosphate (ATP) production or a
      decrease in ATP utilisation under conditions of constant myocardial oxygen
      consumption (MVO2). These experiments were performed to test the hypotheses that
      (1) acute hibernation could be modelled in an isolated perfused rat heart
      exhibiting metabolic adaptation; and (2) recovery of phosphocreatine could be
      explained by alterations in relative creatine kinase flux during hibernation.
      METHODS: Nuclear magnetic resonance techniques were used in an isolated, perfused
      rat heart model of acute hibernation to determine the changes in metabolites and
      creatine kinase kinetics. A flow reduction from 12.5 to 5.4 ml.min-1 was employed
      for two hours, followed by reperfusion. RESULTS: Reduction of flow resulted in a
      stable 44% reduction in rate-pressure product. Phosphocreatine had a significant
      decrease of 9% within the first 15 minutes of ischaemia, but recovered to control
      values by the end of ischaemia. ATP and [ADP], although unchanged in the early
      phase of ischaemia, were progressively reduced during the later phase of
      ischaemia. Intracellular pH fell from 6.99(0.04) to 6.92(0.03) after 15 minutes
      of ischaemia with little recovery. Saturation transfer measurements showed
      stability of the forward flux in the creatine kinase reaction during ischaemia,
      but a progressive reduction in the calculated reverse flux. CONCLUSIONS: These
      data show that acute hibernation can be modelled in an isolated perfused heart,
      exhibiting recovery of phosphocreatine despite progressive reductions in ATP.
      Metabolic changes during acute hibernation have a phasic response characterised
      by an early ischaemic phase and a later adaptive phase. There is a time related
      change in measured creatine kinase flux, consistent with a differential change in
      either ATP production via an increase in MB creatine kinase isoenzyme or a shift
      in the activity of mitochondrial v cytosolic creatine kinase, a reduction in ATP
      utilisation via increased efficiency of ATP utilisation at the myofibril, or a
      changing contribution of glycolytically produced ATP.

PMID- 8287417
TI  - Antioxidant defences in rat, pig, guinea pig, and human hearts: comparison with
      xanthine oxidoreductase activity.
AB  - OBJECTIVE: Cardiac injury, related to ischaemia and reperfusion, may be caused by
      the action of oxygen free radicals. Xanthine oxidoreductase activity may be an
      important free radical source. During cardiac ischaemia, the native dehydrogenase
      form may be converted to the oxidase form, which uses molecular oxygen to form
      superoxide radicals. Superoxide dismutase converts the radicals to H2O2, which is
      detoxified by catalase and glutathione peroxidase. In view of the large
      differences in xanthine oxidoreductase in various species, the activity of these
      antioxidant enzymes was investigated. METHODS: Normal rodent and porcine as well
      as explanted human hearts were perfused according to Langendorff. After a 30
      minute stabilisation period, hypoxanthine was added to the perfusion buffer to
      estimate xanthine oxidoreductase. Hearts or biopsies were freeze clamped after 90
      minutes. Effluent xanthine and urate were assayed with high performance liquid
      chromatography; tissue reduced glutathione content and the activity of superoxide
      dismutase, catalase, glutathione peroxidase, and glutathione reductase were
      determined spectrophotometrically. Apparent xanthine oxidoreductase was
      calculated as xanthine +2 x urate production. RESULTS: Xanthine oxidoreductase
      was (mU.g-1 protein, mean(SEM), n = 5-7): rat, 470(40); guinea pig, 270(41); pig
      < 1.5; and human, 5.4(1.0). Superoxide dismutase activities were (U.g-1 protein):
      rat, 13,370(1030); guinea pig, 10,100(1110); pig, 12,800(450); and human,
      7400(450). Catalase activity (k < or = 10.g-1 protein) was low in all species
      studied. Glutathione peroxidase activity was 93(7) U.g-1 protein in rat heart,
      and 10 x lower in the other species. Glutathione reductase activity was (U.g-1
      protein): rat, 15.0(1.6); guinea pig, 10.4(1.3); pig, 16.0(1.5); and human,
      26.6(2.0). Tissue reduced glutathione concentrations were (mumol.g-1 protein):
      rat, 13.5(0.8); guinea pig, 18.5(0.9); pig, 11.1(2.9); and human 17.2(1.7).
      CONCLUSIONS: Considerable species differences in xanthine oxidoreductase activity
      exist, contrasting with the smaller variations in antioxidant enzyme activities.
      In the species examined catalase activities were very low. Rat hearts are far
      better protected against H2O2 than the other three species. Xanthine
      oxidoreductase induced free-radical damage probably plays a minor role in pig and
      human hearts. Human myocardium seems less protected against superoxide radicals.

PMID- 8287418
TI  - Disassociation of intrinsic and haemodynamic responses in stenotic arteries.
AB  - OBJECTIVE: In stenotic arteries, constriction can decrease intraluminal pressure,
      which in turn can further decrease vessel size. Because of these pressure
      changes, the hypothesis that haemodynamic responses may be significantly
      different from intrinsic smooth muscle responses in stenotic arteries was tested.
      METHODS: In rabbits (n = 16), one iliac artery was denuded (stenotic), and the
      other iliac artery was untouched (hypercholesterolaemic). The rabbits were placed
      on a 2% cholesterol diet for three weeks. Iliac arteries from these and normal (n
      = 8) rabbits were removed and studied as rings or perfused segments. RESULTS: In
      arterial rings, maximal isometric tension in response to noradrenaline was
      significantly (p < 0.05) greater in hypercholesterolaemic [0.59(SEM 0.03) x 10(6)
      dynes.cm-2] and normal arteries 0.63(0.04) compared with stenotic arteries
      [0.28(0.04)]. Normal [EC50 = 6.99(0.07), -log(M)] and hypercholesterolaemic [EC50
      = 7.00(0.12)] rings were more sensitive (p < 0.05) to noradrenaline than stenotic
      rings [EC50 = 6.49(0.24)]. All arterial rings vasodilated in response to glyceryl
      trinitrate, and changes in isometric tension occurred over a 1000-fold change in
      noradrenaline or glyceryl trinitrate concentration. In normal and
      hypercholesterolaemic arteries, flow was unaltered even at the highest
      noradrenaline concentration. In stenotic arteries, noradrenaline decreased distal
      pressure from 76.9(5.4) to 24.3(7.3) mm Hg (p < 0.05) and flow from 17.9(1.6) to
      6.4(1.8) ml.min-1 (p < 0.05). After noradrenaline decreased flow, glyceryl
      trinitrate did not always successfully vasodilate the stenotic arteries and
      thereby re-establish flow. Lastly, in stenotic arteries, most of the haemodynamic
      response occurred at one incremental dose of noradrenaline or glyceryl
      trinitrate. CONCLUSION: Fundamentally different haemodynamic responses occur in
      stenotic v normal and hypercholesterolaemic arteries. As the intrinsic smooth
      muscle responses (from the stenotic rings) are weaker, the augmented responses in
      whole stenotic segments are probably related to the intraluminal pressure
      changes.

PMID- 8287419
TI  - Hypersensitivity of Gi protein mediated muscarinic receptor adenylyl cyclase in
      chronic ischaemic heart failure in the rat.
AB  - OBJECTIVE: The aim was to study the Gi protein mediated muscarinic signalling
      system in the myocardium of rats with chronic ischaemic heart failure. METHODS:
      Chronic ischaemic heart failure was induced by myocardial ischaemia (four weeks
      after coronary artery ligation) in rats. The densities and agonist affinities of
      muscarinic receptors, and the functional activity and concentration of Gi
      proteins were studied. RESULTS: In failing hearts, the activity of adenylyl
      cyclase stimulated by guanyliminodiphosphate (Gpp(NH)p) was decreased by 46%.
      Stimulated activities of adenylyl cyclase by both sodium fluoride and forskolin,
      however, remained unchanged. Carbachol depressed forskolin stimulated adenylyl
      cyclase more in membranes from failing hearts than those from normal hearts. The
      functional level of Gs protein as measured by a reconstitution assay in
      sarcolemmal membrane did not differ between the two groups. Furthermore,
      muscarinic receptors exhibited superhigh and low affinities for agonist in
      failing hearts whereas those in control hearts displayed only high and low
      affinities. No significant difference in the peptide equivalent amount of
      membrane bound Gi protein was found in either group. CONCLUSIONS: The
      experimental chronic failing heart due to myocardial ischaemia showed a depressed
      myocardial adenylyl cyclase signalling system. This may be due to the
      hypersensitivity of the Gi protein mediated muscarinic receptor-adenylyl cyclase
      system as shown by the increased inhibition of Gpp(NH)p mediated adenylyl
      cyclase, more potent inhibition of stimulated adenylyl cyclase by carbachol, and
      the superhigh affinity of the muscarinic receptors for carbachol.

PMID- 8287420
TI  - Preconditioning with supply-demand imbalance limits infarct size in dog heart.
AB  - OBJECTIVE: The aim was to examine whether an absolute reduction in energy supply
      is required for preconditioning against myocardial infarction, and whether an
      episode of increased adrenergic activity with or without supply-demand imbalance
      is capable of triggering cardioprotection. METHODS: 41 anaesthetised dogs were
      subjected to 60 min left circumflex artery occlusion followed by 5 h reperfusion
      (control group, n = 8). The left stellate cardiac nerve was stimulated for 5 min
      starting 10 min before coronary occlusion in the stimulation group (STIM group, n
      = 8). The left circumflex artery flow increase that normally accompanies
      adrenergic stimulation was prevented by a pneumatic occluder in another group
      (STIM-R group, n = 8). Infarct size and area at risk were determined by triphenyl
      tetrazolium chloride staining and Evans blue dye, respectively. Regional
      myocardial blood flow during ischaemia and during stimulation (STIM-R group) was
      measured with radioactive microspheres. RESULTS: In the STIM group, adrenergic
      stimulation increased the coronary blood flow by approximately twofold from
      baseline. In the STIM-R group, transmural myocardial blood flow in the flow
      restricted left circumflex artery region was 64% of the flow to the non-flow
      restricted left anterior descending coronary artery region. Haemodynamic
      variables were not different among the experimental groups except during
      adrenergic stimulation. Collateral blood flow and area at risk were comparable
      among the three groups. Infarct size as a percentage of area at risk (%IS/AAR)
      was significantly smaller in the STIM-R group [7.6(3.2)%] than in the control
      group [27.9(7.3)%], whereas %IS/AAR in the STIM group [21.7(4.1)%] was not.
      Furthermore, the regression line between collateral blood flow and %IS/AAR was
      significantly shifted downward in the STIM-R group, but not in the STIM group.
      CONCLUSIONS: (1) Transient energy supply-demand imbalance triggers infarct size
      limitation; an absolute reduction in energy supply is not required for
      preconditioning. (2) Increased adrenergic activity without supply-demand
      imbalance seems unable to trigger appreciable cardioprotection.

PMID- 8287421
TI  - Ischaemic preconditioning and myocardial adaptation to ischaemia.

PMID- 8287422
TI  - Collateral flow and the acute phase treatment of myocardial infarction in
      diabetic patients.

PMID- 8287423
TI  - Na+/H+ exchange and regulation of intracellular Ca2+.

PMID- 8287424
TI  - Reperfusion arrhythmias.

PMID- 8287425
TI  - Reperfusion arrhythmias.

PMID- 8287426
TI  - Reperfusion arrhythmias.

PMID- 8287427
TI  - Reperfusion arrhythmias.

PMID- 8287428
TI  - Reperfusion arrhythmias.

PMID- 8287429
TI  - Recovery of hypoxic neonatal hearts after cardioplegic arrest.

PMID- 8287430
TI  - Myocardial oedema: a preventable cause of reperfusion injury?
AB  - Myocardial ischaemia increases cellular and extracellular osmolarity, alters
      membrane permeability to ions and causes moderate cell swelling and interstitial
      oedema. Ischaemia also reduces the mechanical resistance of the sarcolemma of
      myocytes, probably as a result of proteolytic digestion of the connections
      between cell membrane and the cellular scaffold. During reperfusion, the abrupt
      normalisation of extracellular osmotic pressure results in marked osmotic cell
      swelling. In the clinical situation, the ability of mechanical stress imposed by
      cell swelling to disrupt the weakened sarcolemma of viable myocytes during
      reperfusion has not been definitively established. Observations demonstrating the
      important role of mechanical stress caused by contraction and cell to cell
      interaction in myocyte necrosis support the hypothesis that osmotic cell swelling
      may actually produce lethal reperfusion injury. This hypothesis has been
      investigated by analysing the effect of hyperosmotic reperfusion with mannitol on
      final infarct size after coronary occlusion. Studies using highly hyperosmotic
      reperfusion after relatively short periods of ischaemia have yielded positive
      results, while studies using intravenous mannitol at the time of reperfusion, and
      more closely resembling clinical situations, have failed to detect any beneficial
      effect. Myocardial oedema could also contribute to postischaemic functional
      derangements, such as reperfusion arrhythmias and stunning, and could modify the
      passive mechanical properties of the infarcts and alter ventricular remodelling.
      Interventions aimed to limit myocardial oedema will probably not play a role as a
      co-adjuvant therapy in patients with acute myocardial infarction receiving
      thrombolytic treatment. However, they should probably form part of controlled
      reperfusion strategies to be evaluated in patients with acute myocardial
      infarction in whom reperfusion is accomplished by percutaneous transcoronary
      angioplasty or surgery.

PMID- 8287431
TI  - An explanation for the reported observation that ATP dependent potassium channel
      openers fail to mimic preconditioning.

PMID- 8287432
TI  - An explanation for the reported observation that ATP dependent potassium channel
      openers mimic preconditioning.

PMID- 8287433
TI  - Effect of ischaemia and role of eicosanoids in release of atrial natriuretic
      factor from rat heart.
AB  - OBJECTIVE: The aim was to investigate (1) the relationship between atrial
      natriuretic factor (ANF) release and the extent of ischaemia-hypoxia, and (2) the
      potential role of eicosanoids in ANF release during global ischaemia,
      particularly the cyclo-oxygenase derivatives (prostaglandins) and the
      lipoxygenase derivatives (leukotrienes). METHODS: Using an isolated perfused,
      spontaneously beating rat heart, global ischaemia was achieved by the reduction
      of perfusion flow rate relative to basal flow rate. ANF was measured by
      radioimmunoassay. RESULTS: A decrease in perfusion flow rate by 75-80% to a final
      value of 2-2.5 ml.min-1.g-1 heart (n = 6) caused a gradual but sustained increase
      of ANF release which reached a plateau after 12 min, attaining a peak value of
      89.9 (SEM 26.6)% over baseline. A decrease in perfusion flow rate by 55-60% (n =
      5) also resulted in an increased ANF secretion, with a peak of 125.6(23.2)% over
      baseline at 14 min. A decrease in perfusion flow rate by 25-30% to a final value
      of 5-6.75 ml.min-1.g-1 heart (n = 4) showed no change in ANF release. The mean
      basal value of ANF release was 8.23(2.39) ng.min-1.g-1 heart (n = 26). In a
      separate series of experiments using a reduction of 55-60% in perfusion flow rate
      but with the addition to the perfusion medium of the specific cyclo-oxygenase
      inhibitor meclofenamate 10 microM (n = 5) or the lipoxygenase inhibitor
      nordihydroguaiaretic acid 10 microM (n = 5), no increase in ANF release occurred
      during the period of global ischaemia. Neither inhibitor affected ANF release
      during basal perfusion rates (7-9 ml.min-1.g-1 heart). CONCLUSIONS: ANF released
      in response to global ischaemia is likely to be mediated by prostanoids generated
      via the cyclo-oxygenase pathway and leukotrienes generated via the lipoxygenase
      pathway. Both pathways may provide important paracrine/autacoid regulatory roles
      for the protection of the heart during ischaemia by stimulating ANF release, with
      the subsequent beneficial effects of the peptide on peripheral tissues,
      ultimately leading to a reduction in load on the heart.

PMID- 8287434
TI  - Cellular electrophysiology of WAY-123,398, a new class III antiarrhythmic agent:
      specificity of IK block and lack of reverse use dependence in cat ventricular
      myocytes.
AB  - OBJECTIVE: The objectives were (a) to evaluate the effects of WAY-123,398, a new
      class III antiarrhythmic agent, on the action potential of canine Purkinje fibres
      in comparison with dofetilide, E-4031, and dl-sotalol, and (b) to characterise
      the mechanism of the class III action by studying its effects on several ionic
      currents in isolated cat myocytes. METHODS: Transmembrane potentials in Purkinje
      fibres were studied with standard microelectrodes filled with 3M KCl. Myocytes
      were isolated by enzymatic disaggregation with collagenase and current recordings
      were obtained by voltage clamp with either the nystatin perforated patch
      technique or the usual whole cell configuration. RESULTS: WAY-123,398 prolonged
      action potential duration (APD) in Purkinje fibres and in cat ventricular
      myocytes without altering other variables of the action potential; in Purkinje
      fibres the concentration producing a 20% prolongation of APD-60 mV at a basic
      cycle length of 1000 ms was 0.2 microM. After depolarising voltage steps, the
      delayed rectifier (IK) peak tail currents in cat myocytes were blocked with IC50
      = 0.1 microM. The block was unaffected by varying the duration (200 to 500 ms) or
      the frequency (0.4 to 2.5 Hz) of the depolarising steps. A much higher
      concentration of WAY-123,398 (10 microM) did not have effects on the L type Ca
      current (ICa-L), and on the inward rectifier (IK1) and transient outward (I(to))
      K currents. CONCLUSIONS: The results indicate that WAY-123,398 is an effective
      and specific class III agent devoid of class I activity, and suggest that WAY
      123,398 prolongs cardiac repolarisation by specifically blocking the delayed
      rectifier current (IK). The block was unchanged over a range of frequencies and
      duration of depolarisation, showing no evidence of "reverse use dependence" of
      block.

PMID- 8287435
TI  - Endogenous adenosine and coronary vasoconstriction in hypoperfused myocardium
      during exercise.
AB  - OBJECTIVE: The coronary circulation has been shown to remain responsive to
      vasodilator and vasoconstrictor stimuli during myocardial ischaemia. The aim of
      this study was to investigate whether endogenous adenosine attenuates coronary
      vasoconstriction caused by the thromboxane A2 analogue, U46619. METHODS: Nine
      chronically instrumented dogs were studied during treadmill exercise in the
      presence of a coronary stenosis which resulted in distal left circumflex coronary
      artery hypoperfusion. Myocardial blood flow was assessed with radioactive
      microspheres during exercise prior to and during intracoronary infusion of U46619
      (0.01 microgram.kg-1 x min-1), in the absence and the presence of adenosine
      receptor blockade with intravenous 8-phenyltheophylline (5 mg.kg-1) and
      intracoronary adenosine deaminase (50 units.kg-1). Distal coronary pressure was
      maintained constant during the control stenosis and the three interventions, at
      49(SEM 3), 50(3), 50(3), and 50(3) mm Hg. RESULTS: During control exercise mean
      myocardial blood flow was 0.91(0.09) ml.min-1 x g-1 in the stenosis region and
      2.54(0.28) in the normal region. With no change in distal coronary pressure,
      U46619 decreased mean myocardial blood flow to 0.70(0.10) ml.min-1 x g-1 (p <
      0.05). Adenosine blockade alone decreased myocardial blood flow in the stenosis
      region to 0.60(0.07) ml.min-1 x g-1 (p < 0.05 v control stenosis), indicating
      that endogenous adenosine contributed to coronary vasodilatation in the ischaemic
      region. However, adenosine blockade did not augment the vasoconstriction in
      response to U46619 [mean myocardial blood flow 0.49(0.05) ml.min-1 x g-1],
      indicating that endogenous adenosine did not attenuate the vasoconstriction
      caused by U46619. CONCLUSIONS: Endogenous adenosine contributed to dilatation of
      resistance vessels in hypoperfused myocardium of exercising dogs in the absence
      as well as in the presence of U46619. However, endogenous adenosine did not
      attenuate the magnitude of the vasoconstrictor response to U46619. These findings
      are best explained by observations that thromboxane A2 and adenosine act on
      coronary vascular segments of different size.

PMID- 8287436
TI  - Coordinate gene expression during neonatal rat heart development. A possible role
      for the myocyte in extracellular matrix biogenesis and capillary angiogenesis.
AB  - OBJECTIVE: Neonatal heart development is a period of active extracellular matrix
      deposition and capillary angiogenesis which follows the cessation of ventricular
      myocyte proliferation. The aim was to determine whether coordinate expression of
      growth factors by the ventricular myocyte could function to inhibit myocyte
      proliferation directly as well as indirectly by paracrine stimulation of non
      myocyte extracellular matrix deposition and capillary angiogenesis. METHODS:
      Immunohistochemistry and northern blot hybridisations were performed on
      ventricular samples from fetal to mature animals of the spontaneously
      hypertensive (SHR) and normotensive control Wistar Kyoto (WKY) strains. RESULTS:
      Ventricular expression of types I, III, and IV collagen genes reached their
      "maximum" within the first 2-3 postnatal weeks and then rapidly declined.
      Expression of TGF beta 3 and SPARC were found to precede and accompany the
      changes in extracellular matrix gene expression during this same developmental
      period. TGF beta 3 was immunolocalised to fetal cardiomyocytes with very limited
      expression in neonatal/adult non-myocytes. Associated with the neonatal
      expression of TGF beta variants, transcripts for the type 2 IGF receptor
      gradually declined over the first three postnatal weeks. Myocyte TGF beta gene
      expression, latent TGF beta release, and paracrine mechanisms of action could be
      facilitated by residual type 2 IGF receptor expression to help mediate
      stimulation of non-myocyte extracellular matrix synthesis and deposition.
      CONCLUSIONS: Expression of select growth factors, growth factor receptors, and
      components of the extracellular matrix appear to be highly coordinated during
      ventricular remodelling which occurs during neonatal heart development. A
      paradigm is presented which integrates the expression patterns of various myocyte
      derived stimuli and their postulated impact on formation of the structural
      components of the neonatal heart by modulation of myocyte and non-myocyte cell
      types.

PMID- 8287437
TI  - Specific atrial overexpression of G protein coupled human beta 1 adrenoceptors in
      transgenic mice.
AB  - OBJECTIVE: The aim was to develop a transgenic mouse model of atrial beta 1
      adrenoceptor overexpression in order to create atrial alteration of the receptor
      transduction system. METHODS: Transgenic founders were generated after
      microinjection of the transgene construct into the pronucleus of fertilised mouse
      eggs. Heterozygous progeny were screened for RNA expression of the human beta 1
      adrenoceptor gene under the control of a 0.56 kb proximal promoter of the human
      atrial natriuretic factor. One line, out of the three obtained, was selected and
      further characterised for overexpression of the human beta 1 adrenoceptor.
      Polymerase chain reaction was employed to detect beta 1 adrenoceptor mRNA, and
      125I-cyanopindolol (ICYP) binding assays were used to quantify receptors in heart
      membranes. A quantitative autoradiographic ICYP binding technique was also used
      to visualise atrial and ventricular beta adrenoceptors in heart sections.
      RESULTS: The human beta 1 adrenoceptor was overexpressed specifically in the
      atria of transgenic mice. The level of the beta 1 adrenoceptor was 5-10-fold
      higher in transgenic mice compared to basal murine beta 1 adrenoceptors in non
      transgenic control mice. Left and right atrial receptor overexpression was
      confirmed by in vitro autoradiography. The human receptors were able to couple to
      the murine stimulatory G proteins (Gs), as shown by high affinity binding site
      dosage using the beta adrenoceptor agonist isoprenaline. Isoprenaline
      displacement studies allowed the determination of two different affinity sites,
      one of high affinity (KH = 5.8 nM), and one of low affinity (KL = 520 nM). When
      expressed in terms of protein density (fmol.mg-1), atrial transgenic beta 1
      adrenoceptors displayed a threefold increase in high affinity sites (KH) as
      compared to control mice. Preliminary electrocardiographic data showed
      supraventricular premature beats in 6/14 transgenic mice v 2/16 control mice.
      CONCLUSIONS: These transgenic mice may provide a useful pharmacological tool to
      investigate the pathophysiological consequences of the overactivation of atrial
      beta 1 adrenoceptor-adenylyl cyclase signalling system.

PMID- 8287438
TI  - The endothelin-1 receptor antagonist BQ-123 reduces infarct size in a canine
      model of coronary occlusion and reperfusion.
AB  - OBJECTIVE: The aim was to determine the effect of the endothelin-1 receptor
      antagonist, BQ-123, on infarct size in anaesthetised dogs subjected to 90 min of
      left circumflex coronary artery occlusion and 5 h of reperfusion. METHODS: BQ-123
      was given directly into the left circumflex coronary artery at 0.03 or 10
      micrograms.kg-1 x min-1 starting 15 min before coronary occlusion and continuing
      throughout occlusion and reperfusion. Regional myocardial blood flow was
      determined before, during, and after ischaemia. At the end of the study, infarct
      size was determined using triphenyltetrazolium chloride staining. RESULTS:
      Myocardial infarct size was significantly reduced by BQ-123 (40% reduction from
      vehicle infarct size) at both doses used. This cardioprotection occurred despite
      a lack of effect of BQ-123 on peripheral haemodynamic status. BQ-123 also had no
      effect on regional myocardial blood flow in ischaemic and non-ischaemic tissue.
      Both cardioprotective doses of BQ-123 were found to completely abolish the
      coronary constrictor effect of intracoronary endothelin-1 administration.
      CONCLUSIONS: These data indicate that endothelin-1 release during ischaemia may
      be involved in the pathogenesis of myocardial ischaemia and infarction.

PMID- 8287439
TI  - Role of 5-hydroxytryptamine in the progression of monocrotaline induced pulmonary
      hypertension in rats.
AB  - OBJECTIVE: The aim was to clarify the role of serotonin (5-hydroxytryptamine, 5
      HT) in monocrotaline induced pulmonary hypertension. METHODS: Plasma 5-HT levels,
      pulmonary capillary platelet count, and vascular responsiveness to 5-HT were
      evaluated in the model. The effects of the selective 5-HT2 receptor antagonist,
      DV-7028, on the development of pulmonary hypertension were also investigated.
      RESULTS: Plasma 5-HT was raised 12 h to 3 d after monocrotaline administration
      (60 mg.kg-1), coinciding with accumulation of platelets in the pulmonary
      circulation. Isolated pulmonary arteries showed hyperreactivity to 5-HT at 14 and
      21 d after monocrotaline. Administration of DV-7028 (20 mg.kg-1 x d-1) attenuated
      the increase in pulmonary arterial pressure, right ventricular hypertrophy, and
      medial thickening of the pulmonary arteries. CONCLUSIONS: The present study
      suggests that 5-HT released from platelets contributes to the initiation and
      progression of monocrotaline induced pulmonary hypertension.

PMID- 8287440
TI  - Deaminovasopressin has direct and modulatory effects on ventricular automaticity
      in the rat heart.
AB  - OBJECTIVE: Some neuropeptides have direct cardiac effects and also modulate the
      cardiac effects of catecholamines. Vasopressin is an abundantly available
      neuropeptide having well known interactions with catecholamines in vascular
      smooth muscle. The aim of this study was to determine the direct and modulatory
      effects of vasopressin on ventricular automaticity. METHODS: The cardiac effects
      of deaminovasopressin (dAVP), a long acting synthetic analogue of vasopressin,
      were tested on basal and alpha 1 agonist induced changes in automaticity in
      isolated ventricular septal preparations from adult and neonatal rats after
      chronic exposure (10 micrograms.kg-1 x d-1 subcutaneously for 10 d) and acute
      exposure (in vitro bath superfusion with 10(-8) M dAVP for 1 h). RESULTS: Chronic
      exposure to dAVP decreased basal ventricular automaticity in the adult and in 10
      11 d old rats. Although alpha 1 agonists tended to decrease automaticity in adult
      rat heart, prior chronic dAVP exposure altered the chronotropic response to alpha
      1 agonist so that only an increase in automaticity was observed. A similar result
      was seen in adult ventricular septal preparations upon acute superfusion with
      dAVP. Acute dAVP exposure reduced basal ventricular automaticity, and modified
      the alpha 1 adrenergic chronotropic response, such that only an increase in
      automaticity occurred. Acute dAVP exposure in adult ventricular septal
      preparations did not significantly change total alpha 1 adrenergic receptor
      density or antagonist affinity, alpha 1 adrenergic receptor subtype expression,
      or the amount of pertussis toxin sensitive G protein measured in an ADP
      ribosylation assay. CONCLUSION: dAVP not only exerted direct effects of
      chronotropy, but also influenced the expression of alpha 1 adrenergic
      chronotropic responsiveness. If vasopressin has a similar action, this may have
      important implications in instances where levels of this peptide are raised. For
      example, surgical stress and cardiopulmonary bypass are clinical situations
      associated with increases in both vasopressin and catecholamine levels. An
      interaction between the two may contribute to the development of tachyarrhythmias
      in these settings.

PMID- 8287441
TI  - Effect of pregnancy on relaxation of rat aorta to magnesium.
AB  - OBJECTIVE: There is evidence for involvement of the endothelium in magnesium
      induced vasodilatation. In view of the use of magnesium in the treatment of women
      with pre-eclampsia, and because the mechanism of the vascular effects of
      magnesium in pregnancy is not fully understood, this study examined the dilator
      response to magnesium of aortic rings from pregnant and non-pregnant rats. The
      role of the endothelium was also evaluated. METHODS: Rings from descending
      thoracic aorta of pregnant and non-pregnant rats, contracted with either 10(-7) M
      phenylephrine or 40 mM potassium chloride, were relaxed with increasing
      concentrations of MgSO4 in the presence or absence of 10(-6) M indomethacin or
      endothelium. The rings were also contracted to 10(-5) M phenylephrine, in calcium
      free medium containing 0, 1.2, or 4.8 mM MgSO4. RESULTS: The relaxation of aortic
      rings from pregnant rats to MgSO4 was greater when stimulated with potassium
      chloride but that of rings from non-pregnant rats was greater when stimulated
      with phenylephrine. Neither the presence of MgSO4 nor pregnancy had any effect on
      intracellular calcium dependent contraction. The relaxations of rings from either
      pregnant or non-pregnant rats to MgSO4 were not significantly altered by de
      endothelialisation or pretreatment with 10(-6) M indomethacin. CONCLUSIONS: The
      effect of pregnancy on magnesium induced relaxation of rat aortic smooth muscle
      was dependent on the agent used to induce contraction in the tissue, probably
      because pregnancy exerted different actions on receptor and voltage operated
      calcium channels. This effect of pregnancy was independent of either endothelial
      function or prostaglandin synthesis. Neither pregnancy nor the presence of
      magnesium affected the release of intracellular stored calcium.

PMID- 8287442
TI  - Changes in cyclic AMP dependent protein kinase and active stiffness in the rat
      volume overload model of heart hypertrophy.
AB  - OBJECTIVE: The aim was to clarify the role of cyclic AMP dependent protein kinase
      (PKA) and changes in mechanical heart function during development of cardiac
      hypertrophy induced by volume overload. METHODS: Protein and DNA contents, PKA
      activity, and peak systolic stress-strain relationships in hearts from animals
      submitted to aortocaval shunt were assessed as a function of time. Sham operated
      (control) rats were used as controls. RESULTS: Heart weight to body weight ratio
      and cardiac protein content per heart increased from d 7 (p < 0.005 and p < 0.01,
      respectively) reaching their highest values by d 56; the same occurred with
      cardiac DNA content. PKA activity.g-1 tissue in soluble extracts of hearts from
      rats with aortocaval shunt increased by 2.7-fold on d 2 (p < 0.005), reached a
      ninefold peak increase by d 7 (p < 0.0001) and declined to fourfold by d 56 with
      respect to control values. The end peak systolic stress-strain relation slopes
      were: control, 368(SEM 14) g.cm-2 (n = 16); aortocaval shunt values: 2 d, 514(28)
      g.cm-2 (n = 6); 7 d, 579(10) g.cm-2 (n = 7); and 56 d, 554(28) g.cm-2 (n = 7).
      The force generating capacity at 0% strain was also significantly higher in the
      shunt groups as compared to sham operated controls (p < 0.01). Early activation
      of PKA was also confirmed through endogenous cardiac protein phosphorylation. SDS
      PAGE gel electrophoretogram and autoradiography showed more heavily
      phosphorylated bands in aortocaval shunt hearts than in the control group.
      CONCLUSIONS: PKA activity and the slope of systolic stress-strain regression line
      followed a similar trend throughout the study, with an early increase in both
      variables by d 2 in the shunt group, reaching a peak at d 7, and decreasing
      thereafter but remaining higher than in controls. PKA activity appears to be
      related to increased force generating capacity rather than to hypertrophy or
      increased cardiac protein content. Thus PKA activation is an early biochemical
      event after aortocaval shunt, followed later by cardiac hypertrophy. Changes in
      PKA activity showed a similar trend to mechanical heart function over time. These
      findings help to explain the changes in the mechanical properties of the heart
      preceding the development of cardiac hypertrophy in the rat model of volume
      overload.

PMID- 8287443
TI  - Characterisation of regional myocardial dynamics during mechanical alternans in
      heart of anaesthetised pig.
AB  - OBJECTIVE: The aim was to investigate the behaviour of regional myocardium during
      mechanical alternans in a multidirectional manner. METHODS: Mechanical alternans
      was induced in 12 anaesthetised open chested pigs by rapid atrial pacing. In
      contrast to previous studies, regional mechanical activity was simultaneously
      assessed at up to three different sites on the left ventricle using epicardial
      measuring devices able to provide multidirectional information on segment motion.
      Pressure-length loops were plotted to assess different patterns of segmental
      motion. The integral of pressure and length was calculated to obtain a regional
      work index for each beat. RESULTS: Pressure-length loops revealed profound
      abnormalities in segment motion and work index during regional mechanical
      alternans. Myocardial segments either performed alternate amounts of positive
      work on each beat or alternate amounts of positive and negative work on each
      beat. Alternating segments contracted out of phase with each other and were
      occasionally stretched during systole. CONCLUSIONS: The spatio-temporal
      heterogeneity of regional mechanical behaviour is greatly increased during
      mechanical alternans.

PMID- 8287444
TI  - Inhibition of glycolysis or increased perfusate H+ buffering capacity, but not
      their combination, attenuates myocardial stunning.
AB  - OBJECTIVE: Both inhibition of glycolysis and enhancement of the H+ buffering
      capacity of the perfusate during ischaemia reduce myocardial reperfusion injury.
      The aim of the study was to investigate whether these manoeuvres, performed
      separately or together, could reduce myocardial stunning after brief global
      ischaemia. METHODS: The hearts of male Sprague-Dawley rats were preperfused for
      10 min with oxygenated or hypoxic buffer (pH 7.4) containing 100 mM sucrose, 100
      mM HEPES, or 5 mM 2-deoxyglucose plus 100 mM sucrose, followed by 15 min of total
      ischaemia and 30 min of reperfusion. In some hearts, 5 mM 2-deoxyglucose was
      combined with 100 mM HEPES during the 10 min preperfusion period. RESULTS: Brief
      hypoxic preperfusion, 2-deoxyglucose, or HEPES reduced myocardial stunning as
      well as improving the metabolic recovery and reducing Ca2+ overload after
      reperfusion. These changes were associated with a smaller increase in
      intracellular Na+ and a smaller decrease of coronary effluent pH at the end of
      ischaemia. In contrast, the combination of HEPES with hypoxic preperfusion or 2
      deoxyglucose depressed functional recovery and increased the intracellular Na+
      level at the end of ischaemia as well as increasing Ca2+ overload after
      reperfusion. This happened even though the decrease in coronary effluent pH was
      attenuated to the same extent as before. CONCLUSIONS: Both inhibition of
      glycolysis and enhancement of the perfusate H+ buffering capacity before
      ischaemia attenuated myocardial stunning, but the protective effect of each
      manoeuvre was lost when they were combined.

PMID- 8287445
TI  - Vascular relaxation and cyclic guanosine monophosphate in a rat model of high
      output heart failure.
AB  - OBJECTIVE: Low output heart failure induces abnormalities of endothelium
      dependent vasodilation, but the mechanisms responsible for this remain unclear.
      As blood flow can alter endothelial cell function, in particular nitric oxide
      (NO) release, the activity of endothelium derived relaxing factor (EDRF) was
      investigated in a rat model of high output heart failure. METHODS: The thoracic
      aorta upstream of an aorto-caval fistula in rats was submitted to hormonal
      changes (similar to those in heart failure) and to high blood flow (opposite to
      that found in low output heart failure). Functional and biochemical arterial
      properties were studied in aorto-caval fistula rats and in sham operated rats
      three months after operation. The vascular responses were studied by exposing
      aortic segments from fistula and sham operated rats to increasing concentrations
      of agonists. Aortic cyclic guanosine monophosphate (cGMP) concentration was
      assessed as an index of NO synthase activity. The effect of NO synthase blockade
      on functional and biochemical arterial properties was also studied. RESULTS:
      Plasma atrial natriuretic factor (ANF) was increased in fistula rats compared to
      sham operated rats. The concentrations of acetylcholine or the calcium ionophore
      A23187 required to produce 10% and 50% maximum relaxation (EC10 and EC50) were
      similar in the two groups. Relaxation in response to low concentrations of Sin-1
      (an NO donor) was shifted rightwards in fistula rats and EC10 was greater than in
      the controls. The aortic cGMP concentration was higher in aorto-caval fistula
      rats than in sham operated rats (p = 0.008). The differences between aorto-caval
      fistula rats and sham operated rats were probably the result of increased basal
      EDRF-NO release in the former, since NO synthase blockade abolished the
      differences in both aortic cGMP and the dose-response curve to Sin-1.
      CONCLUSIONS: The arterial wall upstream of a chronic aorto-caval fistula has
      increased cGMP content and hyposensitivity to Sin-1, which may be due to enhanced
      basal EDRF-NO release. These changes, strikingly different from those found in
      the low output heart failure, suggest that haemodynamic rather than
      neuroendocrine factors play a determinant role in the altered vasodilator
      response in heart failure.

PMID- 8287446
TI  - Transient outward current in human and rat ventricular myocytes.
AB  - OBJECTIVE: The aim was to investigate transient outward currents (I(to)) in
      single myocytes isolated from human heart muscle specimens which were obtained
      either from patients in terminal heart failure receiving a transplant or from
      multiorgan donors whose hearts were not suitable for transplantation. METHODS:
      Using the whole cell patch clamp technique, depolarisation dependent I(to) was
      investigated in these myocytes, and its electrophysiological characteristics
      compared to I(to) of rat myocytes. RESULTS: I(to) was observed in ventricular
      myocytes isolated from failing and non-failing human hearts. The current density
      of I(to) was similar in cells from failing and non-failing hearts [at +60 mV:
      7.9(SEM 1.0) pA.pF-1, n = 9, and 8.7(1.2) pA.pF-1, n = 8, respectively], but
      smaller in human than in normal rat myocytes, ie, 8.2(0.7) pA.pF-1 (n = 17) v
      19.9(2.8) pA.pF-1 (n = 12, six hearts), respectively. Half maximum activation was
      found at more positive potentials in human than in rat cells, at +21.2(2.0) v
      +6.4(1.3) mV. In human myocytes, the fraction of non-inactivating outward current
      at the end of 300 ms long clamp steps was smaller than in rat cells, ie, 22(5%)
      of peak I(to) in human (n = 17) and 39(5%) in rat cells (n = 12). The potential
      of half maximum steady state inactivation of rapidly inactivating I(to) in the
      presence of 0.1 mM Cd2+ was -21.4(0.7) mV in human (n = 15, five hearts), and 
      35.3(1.0) mV in rat cells (n = 12, six hearts). The late component of outward
      current showed no potential dependent inactivation in human cells, but underwent
      steady state inactivation at all potentials positive to -100 mV in rat myocytes.
      At -100 mV, recovery of I(to) from inactivation took place with a similar time
      constant, ie, 18(2) ms (n = 7), 24(2) ms (n = 6), and 25(2) ms (n = 4) in cells
      from three failing and two non-failing human hearts, and from two normal rat
      hearts, respectively. CONCLUSIONS: In a limited number of cells, I(to) in human
      ventricular myocytes shows no dramatic differences between cells derived from
      failing and non-failing hearts. The characteristics of I(to) in human cells were
      similar though not identical to I(to) in rat heart cells. This current may be a
      potential target for antiarrhythmic drug action.

PMID- 8287447
TI  - Adenosine and A1 selective agonists offer minimal protection against ischaemic
      injury to isolated rat cardiomyocytes.
AB  - OBJECTIVE: The aim was to determine if isolated rat cardiomyocytes could be
      protected from ischaemic cell death by preincubation with adenosine or adenosine
      agonists. METHODS: Cardiomyocytes isolated from rat hearts were preincubated in
      the presence of adenosine, CCPA (2-chloro-N6-cyclopentyladenosine), or carbachol
      prior to concentration into an ischaemic slurry. Effects of glycolysis and of
      isoprenaline were determined by addition of iodoacetic acid or isoprenaline to
      the ischaemic incubates and by exclusion of glucose from all media. Rates of
      ischaemic contracture were determined and survival of the myocytes versus paired
      control preparations was determined after various times of ischaemia, following
      resuspension of the cells in isotonic or hypotonic media. RESULTS: Adenosine and
      CCPA produced only a small reduction of the rates of contracture and death of
      isolated myocytes. Carbachol gave no significant protection. Neither the degree
      of injury of control cells nor the amount of protection by CCPA was altered in
      the presence of added isoprenaline. Protection was abolished by the A1 receptor
      blocker sulphophenyl theophylline, iodoacetic acid, and exclusion of glucose.
      CONCLUSIONS: Adenosine and adenosine agonists afford a minimal degree of
      protection to ischaemic isolated myocytes by a glucose dependent mechanism. This
      protection does not appear to account for the larger degree of protection seen in
      intact hearts, following similar preconditioning protocols. The failure of
      adenosine to protect may be related to the quiescent state of isolated
      cardiomyocytes, or be species specific in that adenosine may not be the trigger
      for preconditioning in rats.

PMID- 8287448
TI  - A role for depolarisation induced calcium entry on the Na-Ca exchange in
      triggering intracellular calcium release and contraction in rat ventricular
      myocytes.
AB  - OBJECTIVE: The aim was to test whether depolarisation-induced calcium entry on
      the Na-Ca exchange is able to trigger calcium release from the sarcoplasmic
      reticulum in rat ventricular myocytes. METHODS: Myocytes were isolated
      enzymatically from the left ventricle of the rat heart. Cells were impaled with
      narrow tipped microelectrodes to minimise intracellular dialysis and maintain
      normal internal ionic conditions. Cells were voltage clamped, contraction was
      measured optically, and in some experiments intracellular calcium was measured
      with Fura-2. RESULTS: When the fast Na current was inactivated by using a holding
      potential of -40 mV, Ca entry via L-type Ca channels was expected to be the only
      mechanism capable of triggering sarcoplasmic reticular Ca release. In this
      situation, blocking L-type Ca channels should have abolished sarcoplasmic
      reticular release and the phasic twitch. However, after 2 min exposure to 20
      microM nifedipine, which abolished the Ca current (ICa) completely, voltage clamp
      depolarisation from -40 mV to 0 mV still elicited 41(SEM 8.9)% of the control
      phasic twitch (n = 22 cells). This shows that there must be another mechanism,
      besides Ca entry via Ca channels, by which membrane depolarisation can trigger
      sarcoplasmic reticular release and the phasic twitch. The phasic twitch that
      remained in the presence of nifedipine increased progressively with the magnitude
      of step depolarisation, required a functional sarcoplasmic reticulum, was
      abolished by 5 mM external nickel, and was sensitive to both the Na and Ca
      transmembrane gradients. CONCLUSIONS: The voltage dependent sarcolemmal Na-Ca
      exchange is predicted theoretically to generate a transient Ca entry at the start
      of a step membrane depolarisation, when membrane potential suddenly becomes more
      positive than the reversal potential of the Na-Ca exchange. The results of this
      study indicate that in rat myocytes with normal internal ions, physiological
      levels of membrane depolarisation generate a sufficient Ca entry on the exchange
      to trigger sarcoplasmic reticular calcium release and contraction. In the absence
      of ICa, this mechanism is capable of triggering a calcium release which leads to
      about 40% of the phasic contraction in cells depolarised from -40 mV to 0 mV. The
      existence of this sarcoplasmic triggering mechanism may have significance for the
      normal control of cardiac muscle contraction.

PMID- 8287449
TI  - Cytotoxic effects of vascular smooth muscle cells of the chimeric toxin, heparin
      binding TGF alpha-Pseudomonas exotoxin.
AB  - OBJECTIVE: Smooth muscle cell proliferation appears to be very important in
      restenosis after angioplasty. A chimeric toxin created by genetically fusing the
      gene encoding TGF alpha (targets the EGF receptor) to the gene encoding
      Pseudomonas exotoxin (PE) preferentially kills rapidly proliferating smooth
      muscle cells. Recently, a heparin binding EGF-like growth factor (HB-EGF) has
      been identified. The HB domain enhances the mitogenic activity for smooth muscle
      cells. The purpose of this study was to design a new chimeric toxin, having both
      heparin binding and EGF receptor binding function, and to determine whether it is
      more cytotoxic to smooth muscle cells. METHODS: By recombinant DNA techniques, a
      new chimeric toxin, HB-TGF alpha-PE4EKDEL, was synthesised. Cytotoxic assays were
      performed by assessing the capacity to inhibit protein synthesis of rat vascular
      smooth muscle cells. RESULTS: The toxin preferentially killed rapidly
      proliferating smooth muscle cells (p < 0.025). The HB domain increased the
      cytotoxicity of the molecule when compared to the other chimeric toxins tested
      against smooth muscle cells. The cytotoxic effect of the new molecule was
      significantly decreased by exogenously added heparin (p < 0.05). CONCLUSIONS: The
      presence of a heparin binding domain increases the smooth muscle cell
      cytotoxicity of the TGF alpha fusion toxin, perhaps because HB-TGF alpha-PE4EKDEL
      functions as a molecule with two ligands. It will be important to determine
      whether the greater smooth muscle cell cytotoxicity that exists in vitro will
      facilitate the specific targeting and killing of rapidly proliferating cells in
      vivo.

PMID- 8287450
TI  - Guidelines for personnel radiation monitoring in the cardiac catheterization
      laboratory. Laboratory Performance Standards Committee of the Society for Cardiac
      Angiography and Interventions.
AB  - The Laboratory Performance Standards Committee of the Society for Cardiac
      Angiography and Interventions has devised guidelines to inform catheterization
      laboratory personnel about appropriate radiation monitoring and protection. A
      personal monitoring dosimeter must be placed over any radiation protective
      garments on the collar near the thyroid. A second dosimeter, worn at the waist
      level under any radiation protective garments, is mandatory for any declared
      pregnant workers exposed to radiation. This dosimeter is recommended, but not
      required, for all personnel in the catheterization laboratory. The limit for
      whole body radiation exposure is stated in terms of the effective dose equivalent
      (EDE). Different formulas are used for calculating the EDE, depending on the
      number of dosimeters worn simultaneously by the individual. Finger dosimeters
      should be worn by personnel whose hands are likely to be directly exposed to the
      x-ray beam. Initial and periodic training in radiation protection is a part of
      good laboratory practice.

PMID- 8287451
TI  - Optimizing surgical backup for multiple simultaneous percutaneous transluminal
      coronary angioplasty procedures.
AB  - At busy interventional centers, it may be difficult to coordinate surgical backup
      for multiple simultaneous PTCA procedures. We sought to determine the actual risk
      of two simultaneous cases requiring surgery, and to identify a group in which
      multiple simultaneous PTCA procedures could be performed at low risk. We
      prospectively applied the ACC/AHA A/B/C lesion classification system and an
      empiric low/medium/high risk classification (based on patients' overall clinical
      picture) to 1,128 PTCA procedures over a 9 month period; 22 of these patients
      (1.9%) went directly from the catheterization laboratory to emergency CABG. The
      incidence of emergency CABG by groups was A-low 1/166, A-medium 1/71, A-high
      0/22, B-low 1/116, B-medium 10/481, B-high 2/52, C-low 2/47, C-medium 3/88, and C
      high 2/85. The patients were divided into two groups: minimal risk (A + B-low:
      3/375 or 0.8%) and increased risk (B-med/high + C: 19/753 or 2.5%). The
      difference between the groups was significant using chi square with an alpha <
      0.05. The risk of two cases requiring surgery at the same time was calculated as
      a function of the number of simultaneous PTCA procedures performed. Six or fewer
      minimal risk PTCA, one increased risk plus up to three minimal risk, and a
      maximum of two increased risk cases were found to have a risk of < 0.001. We
      conclude that it is possible to identify a group of patients with minimal risk,
      in whom multiple simultaneous procedures can be performed with a negligible
      probability of two cases requiring surgery at the same time.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8287452
TI  - Effect of catheter positioning on the variability of measured gradient in aortic
      stenosis.
AB  - The purpose of this study was to quantify the variation in measured aortic valve
      gradient and calculated aortic valve area when different techniques of cardiac
      catheterization were utilized. Hemodynamic assessment of aortic stenosis severity
      requires an accurately determined pressure gradient. In aortic stenosis, the
      presence of intraventricular pressure gradients and downstream pressure recovery
      within the aorta means that a range of aortic valve gradients could be measured
      in a given patient depending upon catheter position and measurement technique. To
      quantify the degree of variation in measured gradient and calculated aortic valve
      area, we generated transvalvular gradients by nine different techniques in 15
      patients (11 men, 4 women; 29-86 years old). Patients were divided into those
      with severe aortic stenosis (aortic valve area < or = 0.6 cm2, n = 6) and those
      with moderately severe aortic stenosis (aortic valve area 0.61-0.90 cm2, n = 9).
      Considerable variation in measured gradient and calculated aortic valve area was
      observed. The maximum variation in gradient was similar in severe and moderately
      severe aortic stenosis groups (33 mm Hg. vs. 32 mm Hg., p = NS). However, the
      variation in gradient as a percent of maximum gradient was greater (P < 0.05) in
      the moderately severe aortic stenosis group. The maximum variation in calculated
      aortic valve area was 0.1 cm2 in the severe group and 0.3 cm2 in the moderately
      severe group (P < 0.01). An intraventricular gradient, present in 13 of 15 (87%)
      patients, was partially responsible for the variation in pressure gradient
      measurement and calculated aortic valve area.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287453
TI  - Balloon angioplasty of totally and subtotally occluded coronary arteries: results
      using the Hydrophillic Terumo Radifocus Guidewire M (glidewire)
AB  - Balloon angioplasty was attempted, using hydrophillic Terumo guidewires, in 52
      totally and subtotally occluded coronary arteries (50 patients), in which
      recanalisation by conventional angioplasty guidewires had failed. Hydrophillic
      guidewires had a crossing success rate of 65.4% (34/52); there was subsequently a
      technical success rate of 56% (29/52) and clinical success of 39% (20/52).
      Dissection of the coronary artery was seen in 16/29 technically successful cases.
      In 12/16 arteries, dissection was small and localised, whereas in 4/16 large and
      extended distally. There was one myocardial infarction and no peri-procedural
      deaths. Eleven out of 29 technically successful cases continued to be regarded as
      successful 12 mo postangioplasty. We conclude that the hydrophillic Terumo
      guidewire can improve the success rate in angioplasty of totally and subtotally
      occluded coronary arteries when conventional wires have failed.

PMID- 8287454
TI  - Selective injection of a left coronary artery arising anomalously from the
      posterior aortic sinus.
AB  - Six cases of anomalous origin of the left main coronary artery arising from the
      posterior or noncoronary aortic sinus have been previously found at autopsy by
      nonselective aortic sinus injection and only once by selective injection. The
      seventh known case of this anomaly is demonstrated by selective injection that
      also reveals distal severe coronary artery disease.

PMID- 8287455
TI  - Multiple spontaneous coronary artery dissections in a middle aged woman: support
      for an underlying eosinophilic arteritis predisposing to intimal disruption.
AB  - A 43-year-old female received tissue plasminogen activator for an acute antero
      apical myocardial infarction. Cardiac catheterization demonstrated three focal
      dissections involving the left anterior descending and circumflex arteries. She
      expired unexpectantly after undergoing emergency coronary artery bypass grafting
      for therapy of an extension of her infarct. To our knowledge, this is the fourth
      report of multiple spontaneous coronary artery dissections and the second in
      which tissue plasminogen activator was administered. The histologic findings and
      their implications are reviewed.

PMID- 8287456
TI  - Aneurysm of the left main coronary artery without obstructive disease: report of
      a case presenting with severe unstable angina and treated with systemic
      thrombolysis.
AB  - A fusiform aneurysm of the left main coronary artery without associated
      obstructive disease was detected in a 77-year-old patient with severe unstable
      angina treated with systemic thrombolysis. The authors emphasize the following
      features: (1) unusual location of the aneurysm, (2) absence of concomitant
      obstruction in this age group, and (3) clinical efficacy of thrombolysis and
      subsequent long-term oral anticoagulation.

PMID- 8287457
TI  - Right coronary artery cirsoid with fistulous connection to the coronary sinus.
AB  - A 61-yr-old woman was referred to our hospital for evaluation of a suspected
      right atrial myxoma. The transesophageal echocardiogram suggested the presence of
      an anomalous right coronary artery with fistulous connection to the coronary
      sinus. At cardiac catheterization, an oxygen step-up in the right atrium
      indicated a 1.3:1.0 left-to-right shunt. Aortic root angiography showed a large
      and calcified right coronary artery cirsoid draining to the coronary sinus, which
      appeared remarkably dilated. In this rare anomaly, cardiac catheterization is
      necessary, not only to quantify the magnitude of the left-to-right shunt, which
      is an important requirement for the indication to surgical treatment, but also to
      confirm the echocardiographic diagnosis.

PMID- 8287458
TI  - Femoral artery catheterization in patients with previous bifemoral grafting.

PMID- 8287459
TI  - Collagen plug hemostatic closure of femoral arterial puncture sites following
      implantation of intracoronary stents.
AB  - Recently a new adjunct to achieving arterial hemostasis has been developed. The
      device consists of a purified bovine collagen plug which when inserted adjacent
      to the arterial wall induces the formation of a hemostatic cap directly over the
      arterial puncture. We have utilized collagen plug hemostasis in 32 patients on 35
      occasions undergoing implantation of intracoronary stents while attempting to
      maintain continuous full anticoagulation. Initial hemostasis was successfully
      achieved in all patients. Moderate sized (5 to 10 cm) hematomas were noted in 4
      patients and large hematomas (> 10 cm) in 3, of whom 2 required vascular repair
      and transfusion. One patient developed a purulent discharge from the puncture
      site which resolved with a brief course of antibiotics. No patient suffered
      femoral arterial occlusion, distal embolization, or venous thrombosis. There were
      no long term access site problems at a mean follow up of 6 months. Repeat
      catheterization utilizing the same femoral artery was performed in 16 patients
      without difficulty. In five of these patients angiography was performed early
      after stent implantation without discontinuation of full anticoagulation and
      collagen closure was utilized a second time. Collagen plug hemostasis is feasible
      after coronary stenting, may allow more aggressive anticoagulation than might
      otherwise be achieved, and may facilitate angiographic restudy early after
      stenting without the need to discontinue anticoagulation.

PMID- 8287460
TI  - Improved anticoagulation management after Palmaz Schatz coronary stent
      implantation by sealing the arterial puncture site with a vascular hemostasis
      device.
AB  - Sealing the arterial puncture site with a vascular hemostasis device has the
      potential to maintain optimal anticoagulation after stent implantation. The level
      of heparinization during the first 3 days after successful stent implantation was
      retrospectively compared between 2 groups of medically treated patients with
      (group A; n = 18) and without (group B; n = 17) a Vasoseal after sheath removal.
      The number of APTTs sampled in group A and B was 233 and 168, respectively.
      Respective mean values of APTT (seconds) in group A and B were 180 +/- 79 and 172
      +/- 91 at day 1 (p = NS), 132 +/- 43 and 125 +/- 61 at day 2 (p = NS) and 123 +/-
      36 and 116 +/- 48 at day 3 (p = NS). More APTTs were suboptimal (< 80 secs) in
      group B (34/168; 20%) compared to group A (17/233; 7%) [p < 0.001]. More patients
      in group B compared to group A had 1 or more (14/17; 82% vs. 8/18; 44%; p =
      0.04), 2 or more (10/17; 59% versus 3/18; 17%; p = 0.02) and 3 or more (8/17; 47%
      vs. 2/18; 11%; p = 0.03) suboptimal APTTs. Bleeding complications were seen in 4
      patients without and in 3 patients with a Vasoseal. Thus application of a
      vascular hemostasis device results in a less variable anticoagulation after
      coronary stenting, but it does not abolish entry site-related bleeding
      complications.

PMID- 8287461
TI  - Spontaneous coronary dissection treated with directional coronary atherectomy.
AB  - We report a case of spontaneous coronary dissection occurring in a middle aged
      male which was treated with thrombolytic therapy and directional coronary
      atherectomy. This technique provides a new option for treating this entity in the
      cardiac catheterization laboratory.

PMID- 8287462
TI  - "Kissing" stents for bifurcational coronary lesion.
AB  - The coronary stents implantation into each vessel of a bifurcational lesion
      ("kissing" stents) in two patients is reported. The first patient had two short
      "kissing" stents implanted in an ostial lesion of the left anterior descending
      and the intermediate branch. The second patient had successful "kissing" stents
      implantation in the bifurcational lesion of the left main coronary artery.

PMID- 8287463
TI  - Technique for shortening angioplasty guide catheter length when therapeutic
      catheter fails to reach target stenosis.
AB  - Occasionally, the usable length of a balloon angioplasty or other therapeutic
      catheter is insufficient to reach the target stenosis. We describe a technique of
      shortening the guide catheter from the proximal end in vivo without removing the
      coronary guidewire. This permits greater projection of the therapeutic catheter
      to reach distal stenoses.

PMID- 8287464
TI  - Miniature angled sub-selective guiding catheter aids in placing guidewire through
      difficult anatomy.
AB  - A method for fabricating and using a "mini" guiding catheter is presented. Use of
      the mini guiding catheter provides the back up support necessary to enable a
      guidewire to traverse difficult anatomy. Use of this device to cross a lesion in
      an acutely angulated circumflex artery is presented.

PMID- 8287465
TI  - Balloon angioplasty of a tissue conduit stenosis after surgical repair of
      anomalous left coronary artery.
AB  - Surgical correction of anomalous coronary arteries may result in late conduit or
      anastamotic stenosis. In this case report, we describe the use of coronary
      angioplasty to dilate a stenosis at the aortic ostium of an intrapulmonary tunnel
      created to correct an anomalous left coronary artery from the pulmonary artery.

PMID- 8287466
TI  - Miniaturized pressure-guide-wire: evaluation in vitro and in isolated hearts.
AB  - The present study focused on the accuracy and reproducability of measurements
      performed with a miniaturized pressure guidewire system (PGWS) under standardized
      in vitro conditions and in an isolated pig heart model. We used a pressure guide
      wire system provided by Pressure Guide, Radi Medical Systems, Uppsala, Sweden.
      Pressures were recorded by a fiber optic pressure sensor located laterally and 3
      cm from the distal end. The basic principle is that the element modulates an
      optical reflection by pressure induced elastic movements. The light source is an
      emitting diode in the control unit. The PGWS replaces a standard 0.018 in.
      guidewire. The PGWS was introduced through a Y-adapter in a recirculating
      perfusion model, consisting of tubing with internal diameters from 1.00 to 4.00
      mm. Different perfusion pressures (range 20-140 mm Hg) were generated by a
      pressure controlled roller pump. RESULTS: Different lumen sizes from 1 to 4 mm
      had no influence on the measurements. a) In a range from 20 to 140 mm Hg no
      significant differences were found between the perfusion pressure and the
      pressures obtained by the PGWS, resulting in an r-value of 0.99 and an equation
      of y = 1.04x + 1.9. b) In pressure measurements proximal and distal of an
      artificial stenoses resulting in gradients from 0 to 100 mm Hg, the PGWS
      correctly identified the pressure difference with an equally high accuracy, 1, 2,
      and 3 cm behind the stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287467
TI  - Use of the porous balloon in porcine coronary arteries: rationale for low
      pressure and volume delivery.
AB  - Using agents administered systemically, attempts to control the restenotic
      myoproliferative response associated with angioplasty have been unsuccessful. The
      porous balloon has the advantage of achieving high local concentrations by
      directly infusing agents into the arterial wall. The purpose of this study is to
      identify any acute and chronic morphological changes in swine coronary arteries
      infused with normal saline through the porous balloon at different driving
      pressures. In order to establish the safety of local arterial wall infusion
      through the porous balloon, swine underwent porous balloon infusion of 3, 6, or
      10 ml of saline at 5 atmospheres, or infusion of 3 ml of normal saline delivered
      at either 2, 5, or 10 atmospheres of pressure into the normal left anterior
      descending and left circumflex arteries. To assess the histopathologic
      alterations induced by the porous balloon, sized 1.1 to 1 with respect to the
      artery, animals were sacrificed either immediately after porous balloon infusion
      or 14 ays later. Acute vessels were evaluated for the presence of medial injury,
      disruption and/or dissection, whereas chronic vessels underwent morphometric
      analysis measuring the residual luminal area (Lumen area/Intimal area+Lumen area)
      and the maximal intimal thickness. Adequate adventitial penetration was confirmed
      by infusing as little as 2-3 ml of methylene blue at 2 atmospheres of pressure.
      Infusion of 3 ml of normal saline at 2 atmospheres resulted in minor focal medial
      edema and disorganization, detected both acutely and 14 days after porous balloon
      infusion. At delivery pressures of 5 or 10 atmospheres, proportionally more acute
      injury was noted and measurable neointimal lesions were observed 2 weeks after
      infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287468
TI  - Concurrent dilatation of mitral and tricuspid valve stenosis using a single Inoue
      balloon: a report of 2 cases.

PMID- 8287469
TI  - Endomyocardial biopsy via the femoral approach.

PMID- 8287470
TI  - It was a very good year for DNA repair.

PMID- 8287471
TI  - HNF-3 beta as a regulator of floor plate development.
AB  - The transcription factor gene HNF-3 beta is expressed in the ventral midline of
      the mouse embryonic neural tube, including the floor plate, a structure important
      for dorsoventral patterning and axonal guidance. To assess HNF-3 beta function,
      the gene has been ectopically expressed in the midbrain/hindbrain of transgenic
      embryos using an En-2 promoter/enhancer. By 18.5 days postcoitum, transgenic
      brains show a range of abnormalities, including absent inferior colliculus and
      reduced cerebellum. Earlier, several genes normally expressed in the floor plate
      (BMP-1, Steel factor, and HNF-3 alpha) are induced within the same ectopic dorsal
      domain as HNF-3 beta, and autoactivation of the endogenous HNF-3 beta is
      observed. Conversely, expression of the dorsal gene Pax-3 is suppressed. Ectopic
      dorsal neuronal differentiation and abnormal dorsal axonal projections are also
      seen. These results suggest that HNF-3 beta is an important regulator of floor
      plate development in vivo.

PMID- 8287472
TI  - Degeneration of skeletal muscle, peripheral nerves, and the central nervous
      system in transgenic mice overexpressing wild-type prion proteins.
AB  - Prion diseases of humans and animals are known to be caused by infection with
      prions containing PrPSc or mutation of the prion protein (PrP) gene. During
      transgenetic studies, we discovered that uninoculated older mice harboring high
      copy numbers of wild-type (wt) PrP transgenes derived from Syrian hamsters (SHa),
      sheep (She), and PrP-B mice developed truncal ataxia, hindlimb paralysis, and
      tremors. These transgenic (Tg) mice exhibited a profound necrotizing myopathy
      involving skeletal muscle, a demyelinating polyneuropathy, and focal vacuolation
      of the central nervous system. Development of disease was dependent on transgene
      dosage. For example, half of all Tg(SHaPrP+/+)7 mice homozygous for the SHaPrP
      transgene array developed disease by approximately 460 days of age, while no
      hemizygous Tg(SHaPrP+/o)7 mice became ill before 650 days. The novel neurologic
      syndrome found in older Tg(wtPrP) mice implies that overexpression of wtPrPC is
      pathogenic and widens the spectrum of prion diseases.

PMID- 8287473
TI  - The saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo
      telomere formation.
AB  - A screen to detect yeast mutants that frequently lost expression of subtelomeric
      genes identified two mutations in PIF1, a gene known to encode a 5' to 3' DNA
      helicase. The loss of expression of subtelomeric genes in pif1 cells was due to
      deletion of the subtelomeric regions of the chromosomes and the generation of new
      telomeres at proximal sites. In pif1 mutants, de novo telomere formation usually
      occurred at sites with very little homology to telomeric DNA. De novo telomere
      formation after HO-induced chromosome breakage also occurred at elevated
      frequencies in pif1 cells. Moreover, mutations in PIF1 caused all telomeres to
      lengthen. These results suggest that the PIF1 helicase is an inhibitor of both de
      novo telomere formation and telomere elongation.

PMID- 8287474
TI  - Position effect variegation at fission yeast centromeres.
AB  - Chromatin structure at Schizosaccharomyces pombe centromeres is unusual. The
      insertion of the ura4 gene within these centromeres resulted in genetically
      identical cells mosaic for its expression. Placement of the ade6 gene within cen1
      or cen3 resulted in red-white sectored colonies, demonstrating the instability of
      gene expression. The occurrence of pink colonies implied that intermediate levels
      of repression were established. Repression of both genes within centromeres was
      temperature sensitive. The chromatin structure of the ura4 gene at centromeres
      was altered, suggesting that the unusual chromatin encroaches into the gene and
      inhibits normal expression. These repressive effects at S. pombe centromeres
      resemble the classical phenomenon of position effect variegation imposed by
      Drosophila heterochromatin on nearby genes. However, since the epigenetic states
      can be set at intermediate levels of expression, a purely euchromatin
      heterochromatin dichotomy does not apply. A model for the epigenetic regulation
      of genes placed within S. pombe centromeres is presented.

PMID- 8287475
TI  - T cell receptor antagonist peptides induce positive selection.
AB  - We have used organ culture of fetal thymic lobes from T cell receptor (TCR)
      transgenic beta 2M(-/-) mice to study the role of peptides in positive selection.
      The TCR used was from a CD8+ T cell specific for ovalbumin 257-264 in the context
      of Kb. Several peptides with the ability to induce positive selection were
      identified. These peptide-selected thymocytes have the same phenotype as mature
      CD8+ T cells and can respond to antigen. Those peptides with the ability to
      induce positive selection were all variants of the antigenic peptide and were
      identified as TCR antagonist peptides for this receptor. One peptide tested, E1,
      induced positive selection on the beta 2M(-/-) background but negative selection
      on the beta 2M(+/-) background. These results show that the process of positive
      selection is exquisitely peptide specific and sensitive to extremely low ligand
      density and support the notion that low efficacy ligands mediate positive
      selection.

PMID- 8287476
TI  - Identification of a small RNA that interacts with the 5' splice site of the
      Trypanosoma brucei spliced leader RNA in vivo.
AB  - In vivo psoralen cross-linking of the trypanosome spliced leader (SL) RNA has led
      to the discovery of a small RNA that we provisionally call the spliced leader
      associated (SLA) RNA. The 72 nt SLA RNA is unlike any known small RNA except for
      a small region that resembles U5 snRNA. The SL/SLA RNA cross-links map to two
      regions, the predominant interactions occurring between the 5' splice site region
      of the SL RNA and a CUUUUA sequence in the SLA RNA. The resemblance between these
      cross-links and interactions of U5 snRNA with cis-spliced pre-mRNAs suggests that
      the SLA RNA may be the trans-splicing analog of U5 snRNA in trypanosomes.

PMID- 8287477
TI  - Splicing of Balbiani ring 1 gene pre-mRNA occurs simultaneously with
      transcription.
AB  - The 40 kb Balbiani ring 1 (BR1) gene is at a given moment transcribed by, on
      average, 120 RNA polymerases. Here we directly assay the excision of introns both
      in the nascent and in the released nucleoplasmic BR1 pre-mRNAs, isolated by
      microdissection. We show that intron 3, located 3 kb from the 5' end of the pre
      mRNA, is excised simultaneous with transcription. Within 2.5 min of transcription
      time, 50% of the pre-mRNA molecules have lost the intron. Intron 4, located 600
      bases from the polyadenylation site, is excised cotranscriptionally in 5%-10% of
      the molecules and after or during release to the nucleoplasm in the remaining
      molecules. Our results demonstrate that spliceosome assembly is a
      cotranscriptional process in vivo and that splicing may occur during
      transcription but also after completed transcription, depending on the position
      of the intron.

PMID- 8287478
TI  - The nature of major histocompatibility complex recognition by gamma delta T
      cells.
AB  - Despite intensive efforts, the general rules for gamma delta T cell recognition
      remain undefined. Here, we take advantage of the detailed knowledge of the
      molecular structure and biosynthetic pathways of major histocompatibility complex
      (MHC) molecules to analyze the recognition properties of the gamma delta T cell
      clones LBK5 (specific for the class II MHC, IEk) and G8 (specific for the
      nonclassical class I MHC, TL10b). We find that the activation of these clones
      requires neither class I nor class II antigen-processing and that peptides do not
      confer specificity. Epitope mapping also shows that the topology of gamma delta T
      cell receptor interaction with the MHC is distinct from that of alpha beta T
      cells. These results suggest that the molecular nature of gamma delta T cell
      recognition is fundamentally different than that of alpha beta T cells.

PMID- 8287479
TI  - Identification of joint molecules that form frequently between homologs but
      rarely between sister chromatids during yeast meiosis.
AB  - We have investigated DNA interactions between homologs and between sister
      chromatids during meiosis in S. cerevisiae. We have detected a DNA species
      containing information from both parental chromosomes at a specific hotspot for
      meiotic recombination and double strand breaks (DSBs). These joint molecules are
      a prominent feature of meiotic prophase. They appear to be a major intermediate
      stage in DSB-promoted recombination, because they occur with appropriate timing
      and require known recombination functions. Other possibilities cannot be
      completely dismissed, however. Most or all joint molecules contain two full
      length nonrecombinant strands from each parental duplex and thus do not consist
      of single Holliday junctions. Joint molecules form between sister chromatids at
      approximately 10% the interhomolog level. Also, joint molecule formation is
      aberrant in a mutant defective in the HOP1 gene, which encodes a meiotic
      chromosome structure component. General models for discrimination between
      homologs and sisters during meiosis are discussed.

PMID- 8287480
TI  - Meiosis-specific formation of joint DNA molecules containing sequences from
      homologous chromosomes.
AB  - All recombination models postulate one or more recombination intermediates that
      are joint molecules containing two homologous parental molecules. A spike of
      branched DNA molecules not seen in DNA from mitotic cells was found in the two
      dimensional gel analysis of meiotic DNA from S. cerevisiae. The mass of molecules
      in the spike, the timing of its appearance and disappearance, and its absence
      from a recombination-defective spo11 mutant are consistent with the hypothesis
      that it contains recombination intermediates. The spike changes in mass as
      predicted for joint molecules containing DNA from homologous chromosomes rather
      than sister chromatids in a strain heterozygous for an RFLP. Finally, joint
      molecules containing DNA from homologous chromosomes were not found, suggesting
      that the block to recombination between homologous sequences occurs prior to the
      formation of joint molecules.

PMID- 8287481
TI  - The basic-helix-loop-helix domain of Drosophila lethal of scute protein is
      sufficient for proneural function and activates neurogenic genes.
AB  - The development of most epidermal sensory organs in Drosophila is controlled by
      achaete and scute, two of the genes of the achaete-scute complex (AS-C). The
      genes of the AS-C encode members of the basic-helix-loop-helix (bHLH) class of
      transcriptional regulators, and their activity defines proneural cell clusters in
      the imaginal discs from which sensory organ mother cells are singled out by a
      process of lateral inhibition. Ectopic expression of lethal of scute, another
      member of the AS-C, normally dispensable for sensory organ development in the
      adult, promotes this process independently of the activity of the other AS-C
      genes. This demonstrates a high degree of functional redundancy of the products
      of the AS-C. Furthermore, neurogenic genes are activated in ectopic proneural
      clusters, allowing development of epidermal progenitor cells. Finally, the bHLH
      domain is necessary and sufficient to mediate the proneural function, to activate
      neurogenic genes, and to allow lateral inhibition.

PMID- 8287482
TI  - Hedgehog is a signaling protein with a key role in patterning Drosophila imaginal
      discs.
AB  - The segment polarity genes hedgehog and engrailed are expressed in identical
      posterior-compartment-specific patterns in both Drosophila embryos and imaginal
      discs. We show here that the hedgehog protein is secreted, and it can cross
      embryo parasegment borders and the anterior-posterior compartment border of
      imaginal discs to neighboring cells that express neither engrailed nor hedgehog.
      In these cells, it is localized in discrete punctate structures that are
      sequestered within the polarized epithelium. Analysis of animals that have
      expressed hedgehog ectopically, or of a mutant that expresses hedgehog abnormally
      in the anterior compartment of the wing disc, indicates that hedgehog is involved
      in regulating patched. In the embryo, hedgehog regulation of patched apparently
      facilitates patched and wingless expression. In the discs, hedgehog regulation of
      patched and other genes in the anterior compartment helps to establish the
      proximodistal axis. We propose that the cell-cell communication mediated by
      hedgehog links the special properties of compartment borders with specification
      of the proximodistal axis in imaginal development.

PMID- 8287483
TI  - The processing of recombination intermediates: mechanistic insights from studies
      of bacterial proteins.

PMID- 8287484
TI  - Preferential induction of IL-4 is determined by the type and duration of
      antigenic stimulation.
AB  - The transition of lymphokine production from IL-2 to IL-4 was investigated with
      antigen-primed lymph node cells (LNC) by observing cytokine release following
      sequential cycles of antigen exposure in vitro. LNC from mice infected with
      Nippostrongylus brasiliensis (Nb), Trichinella spiralis, or primed with giant
      ragweed pollen demonstrated a pattern of dominant IL-2 production at 24 hr;
      however, there was a switch to predominantly IL-4 production within 72 hr
      following the first cycle of in vitro antigenic stimulation. In addition,
      repeated antigenic stimulation with these antigens shifted the pattern to IL-4
      production. In contrast, only IL-2 production was observed after a single cycle
      of in vitro antigenic challenge with haptens (e.g., NP-O-succinimide or
      trimethylammonium hapten) or the naive allogenic spleen cells. Thereafter, the
      lymphokine production pattern gradually changed from IL-2 alone to mixtures of IL
      2 and IL-4, and finally to predominant IL-4 secretion. In contrast, following
      priming with purified protein derivatives (PPD), it was difficult to detect IL-4
      release even after nine successive weekly stimulations. However, activation of
      PPD-primed cells with anti-CD3 antibody resulted in IL-4 secretion. Furthermore,
      Nb-primed T cells, which produced IL-4 alone after repeated antigenic
      stimulation, produced IL-2 when stimulated in the presence of cycloheximide.
      These results suggest that (1) immune populations regulate cytokine production,
      (2) the IL-2/IL-4 profile is dependent on the type and duration of antigenic
      stimulation, and (3) production or accumulation of cycloheximide-sensitive
      proteins is critical for the switch from IL-2 to IL-4 secretion.

PMID- 8287485
TI  - Immobilized anti-TCR mAb induces split functions in a CD8+ CTL clone.
AB  - A signal through the T cell receptor (TCR) without a second costimulatory signal
      provided by antigen-presenting cell (APC) generally causes a state of anergy in
      CD4+ T helper (Th) 1 cells, but not in CD4+ Th2 cells. In contrast, less is known
      about anergic CD8+ T cells. We have examined whether a CD8+ cytotoxic T
      lymphocyte (CTL) clone incapable of producing IL-2 could be rendered into a state
      of unresponsiveness by treatment with immobilized anti-TCR mAb in the absence of
      a secondary stimulation. The CD8+ CTL clone was induced into nonproliferative
      response to subsequent antigen stimulation while it was bound to immobilized anti
      TCR mAb. The immobilized anti-TCR mAb-treated CTL clone also failed to
      significantly produce cytokine with antigen stimulation. In contrast, the ability
      of the CTL clone to specifically lyse target cells was apparently retained. The
      results suggest that there might be intracellular signal pathways via the TCR for
      CTL functions such as proliferative response, cytokine production, and CTL
      killing.

PMID- 8287486
TI  - Human monoclonal lambda light chain protein exhibits specific binding to the
      variable region of monoclonal anti-IgE antibody.
AB  - A monoclonal heterohybridoma cell line (B11-12) was developed by fusing EBV
      transformed lymphocytes from a patient with hyper-IgE syndrome and SHM-D33
      heteromyeloma cells. The resultant heterohybridoma secreted only human lambda L
      chains exhibiting specific binding to mouse monoclonal Ab to human IgE (mAb
      algE). B11-12 bound to four separate mAb-algE, but not to mAb of the same
      isotypes directed to other antigens. The mAb-algE differed in isotype (IgG1;
      IgG2b) demonstrating that B11-12 was recognizing an idiotypic, but not an
      isotypic determinant on the mAb-algE. Human IgE did not inhibit B11-12 binding to
      mAb-algE, suggesting the interaction between B11-12 and mAb-algE involved an
      idiotope outside the combining site of the mAb-algE. Human sera, including serum
      from the donor of the lymphocytes used to produce heterohybridoma B11-12,
      demonstrated the capacity to inhibit B11-12 binding to mAb-algE. This, along with
      the inability of these same sera to directly bind B11-12, suggests that the serum
      contained reactivity similar to B11-12. We propose that B11-12 demonstrates
      specificity resembling an anti-Id to anti-human IgE Ab.

PMID- 8287487
TI  - Inhibition of lymphocyte adherence to rat lacrimal acinar epithelium by
      interleukin-4 and transforming growth factor-beta 1.
AB  - Mature circulating lymphocyte populations specifically bind to lacrimal gland
      acinar epithelium in vitro and this adherence is thought to contribute to the
      accumulation of lymphoid subsets within lacrimal tissue in vivo. The regulatory
      role of interleukin-4 (IL-4) and transforming growth factor-beta (TGF-beta) in
      this adherence process was examined using an in vitro binding assay. Pretreatment
      of thoracic duct lymphocytes (TDLs) with increasing concentrations of IL-4 or TGF
      beta for 1 hr resulted in a dose-dependent inhibition of lymphocyte binding to
      lacrimal gland acinar epithelium. In contrast, the binding of TDLs to high
      endothelial venules of cervical lymph node was not inhibited by either cytokine.
      Further, IL-4 and TGF-beta pretreatment did not alter the expression of lymph
      node or Peyer's patch homing receptors as well as the LFA-1, VLA-4, or CD44
      adhesion molecules on TDLs. These results suggest that the interaction of
      lymphocytes with lacrimal gland acinar epithelium may be regulated by a receptor
      mediated mechanism that differs from those governing HEV recognition.

PMID- 8287488
TI  - The relative contribution of intrathymic inoculation of donor leukocyte
      subpopulations in the induction of specific tolerance.
AB  - We have recently demonstrated that intrathymic (IT) inoculation of ultraviolet-B
      irradiation-modified donor spleen cells induces specific tolerance to organ
      allografts in transiently immunosuppressed adult rats. This study examines the
      splenic leukocyte component that plays a role in the induction of organ-specific
      tolerance when injected into the thymus of an adult animal. Our results showed
      that in the low responder combination of Lewis-to-ACI, IT inoculation of resting
      Lewis T-cells consistently induced specific unresponsiveness to cardiac
      allografts in sublethally irradiated (200 rad total body irradiation) ACI
      recipients while the same was true in the high responder rat combination of WF-to
      Lewis, where recipient rats were transiently immunomodulated with antilymphocyte
      serum. In contrast, IT inoculation of donor B cells, macrophages, or dendritic
      cells in similarly prepared animals failed to prolong graft survival in both the
      low responder (Lewis-to ACI) and the high responder (WF-to-Lewis) rat strain
      combinations. This observation suggests that donor-specific unresponsiveness can
      be readily achieved by IT inoculation of major histocompatibility (MHC) class I
      expressing donor-type resting T-cells rather than by any donor-type antigen
      presenting cells that express MHC class I and II molecules. Extrathymic
      inoculation of T-cells in transiently immunosuppressed recipients failed to
      prevent graft rejection, thus demonstrating the privileged position of the thymus
      in the induction of tolerance. The unresponsive recipients of cardiac allografts
      specifically and permanently accepted donor-type second-set islet allografts,
      thus confirming antigen-specific tolerance in this model. These results suggest
      that manipulation of the immune system through thymic reeducation of the
      developing T-cells by the deliberate introduction of foreign MHC class I cellular
      alloantigens has therapeutic potential in the induction of transplantation
      tolerance in adult animals.

PMID- 8287489
TI  - Gamma delta T cell receptor subsets in the lung of patients with HIV-1 infection.
AB  - In this study the frequency of gamma delta+ cells and their subsets has been
      assessed in bronchoalveolar lavage (BAL) cell populations recovered from 51
      patients at various clinical stages of HIV-1 infection. Thirteen out of the 51
      HIV-1-infected patients showed an increase in the percentage of TCR delta 1+ BAL
      T cells (25.5%). BAL lymphocytes bearing pan-gamma delta antigens were also
      quantitatively increased in 10 patients (19.6%). A strict correlation was
      observed between the degree of CD8 alveolitis and the increase of gamma delta T
      cells. Phenotypic study of BAL gamma delta cells revealed that (a) V delta 2
      related BB3+ cells accounted for the majority of lung gamma delta T cells; (b)
      these cells were CD45RO+ memory cells and expressed a series of adhesion
      molecules; and (c) 29% of BAL gamma delta T cells expressed CD8 surface
      molecules. We also compared the distribution of V delta 2 and V delta 1 subsets
      in paired samples of peripheral blood and BAL fluid. Patients who showed an
      increased number of BB3+ cells in the BAL fluid presented a reversal of the V
      delta 2 to V delta 1 cell ratio in the peripheral blood. By contrast, in the lung
      of normal subjects pulmonary BB3+ and A13+ cells were present in approximately
      the same proportions found in the peripheral blood. Taken together these data
      demonstrate that a redistribution of T cells expressing V delta 2 TCR takes place
      in the lung of a subset of patients with HIV-1 infection and CD8 alveolitis. In
      the pulmonary microenvironment these cells might play a role in the local immune
      response against HIV-1 and/or opportunistic infections.

PMID- 8287490
TI  - Heterogeneous secretory response of phagocytes from different anatomical
      districts to the dimorphic fungus Candida albicans.
AB  - In the present study, we have examined the ability of phagocytes from different
      anatomical districts to discriminate between the two morphogenetic forms of
      Candida albicans. We have demonstrated that resident peritoneal macrophages (RP-M
      phi) and thioglycollate-elicited peritoneal macrophages (TP-M phi) were able to
      distinguish between the hyphal (H-Candida) and the yeast (Y-Candida) form of the
      fungus, since TNF production was observed only upon exposure of RP-M phi and TP-M
      phi to H-Candida. In contrast, splenic macrophages (S-M phi), bone marrow-derived
      macrophages (BM-M phi) and polymorphonuclear neutrophils (PMN) did not
      discriminate between the two forms because S-M phi and PMN produced TNF
      regardless of the morphogenetic status of the fungus, while BM-M phi did not.
      Under the same experimental conditions, we failed to observe IL-1 production from
      any of the phagocytic cell populations examined, with the exception of PMN. This
      implies that the interaction between phagocytes and C. albicans triggers
      differential secretory responses depending upon the morphogenetic status of the
      fungus and the anatomical localization of the immune cells.

PMID- 8287491
TI  - In vitro production of tumor necrosis factor-alpha by adherent human peripheral
      blood mononuclear cells incubated with killed coccidioidal arthroconidia and
      spherules.
AB  - We examined the in vitro production of tumor necrosis factor (TNF) by adherent
      human peripheral blood mononuclear cells (MNL) incubated with arthroconidia or
      spherules derived from the dimorphic fungus Coccidioides immitis. Using a
      bioassay measuring the percentage cytotoxicity of L929 cells, arthroconidia and
      spherules induced the production of measurable amounts of TNF by MNL. Both the
      arthroconidial and spherule preparations contained < 0.01 ng/ml of endotoxin,
      below that needed to induce cytotoxicity in the bioassay. Based on ELISA, the
      vast majority of TNF induced by arthroconidia or spherules was TNF-alpha, with
      minimal production of TNF-beta. These are the first data to show the production
      of TNF in human coccidioidomycosis.

PMID- 8287492
TI  - Inhibition of T cell activation by protein kinase C pseudosubstrates.
AB  - PKC pseudosubstrate consensus sequences can be found in the amino terminal region
      of all the different PKC isoenzymes characterized to date. Here we have used four
      peptides corresponding to the putative pseudosubstrate sequences from the PKC
      isoenzymes alpha, gamma, delta, and epsilon. These peptides showed PKC inhibitory
      activity when tested in a PKC-specific enzyme assay at concentrations of 25 to
      100 microM, similar to what has been reported for the myristylated peptide KRTLR.
      Although the presence of a myristyl group at the amino terminal end of any of
      these peptides is not essential for their inhibitory activity, myristylation
      increased the inhibitory activity significantly. By contrast, the myristylated
      control peptide (GALRQQKNVHEVKN) was not active even at a 100 microM
      concentration. All of the PKC inhibitory peptides were also able to block PKC
      activity in a cell assay as demonstrated by their ability to inhibit the
      induction of IL-2R and TNF-beta expression in Jurkat cells. Finally, we confirmed
      a previous report of the inhibitory activity of the myristylated peptide KRTLR
      and showed that other related peptides (N-m-RLTRK, N-m-RRLKT) are also active in
      these assays.

PMID- 8287493
TI  - Similarities and differences between extrathymic T cells residing in mouse liver
      and intestine.
AB  - Extrathymic T cells in the hepatic sinusoids and intraepithelial lymphocytes
      (IEL) in the intestine of mice have both similar and different properties. In
      this study, both types of extrathymic T cells in mice were further characterized.
      Lymphocytes obtained from systemic immune organs, including the lamina propria
      and Peyer's patches, were also compared. Extrathymic T cells in both the liver
      and the intestine contained a large proportion of gamma delta T cells and
      expressed the alpha alpha homodimer of CD8. They became more prominent in athymic
      nude mice and in normal mice with aging, while disappearing in scid mice.
      Extrathymic T cells in the liver, on the other hand, had TCR of intermediate
      intensity (i.e., intermediate TCR cells) and IL-2 receptor beta-chains (IL-2R
      beta) of high intensity, similar to NK cells, whereas IEL had TCR of bright
      intensity and consisted of cells with both low and high levels of IL-2R beta.
      Thymus-derived T cells did not express IL-2R beta at all, at least at their
      resting conditions. Intermediate TCR cells included double-negative CD4-8- cells
      as well as single-positive cells. In contrast, IEL contained both double-positive
      (DP) CD4+8+ cells and single-positive cells. More precisely, IEL gamma delta T
      cells were mainly IL-2R beta + and single-positive (mainly CD8+), while IEL alpha
      beta T cells were mainly IL-2R beta- and contained both DP CD4+8+ cells and
      single-positive cells. CD4+ cells were more predominant than CD8+ cells in the
      liver, while CD8+ cells were overwhelmingly predominant in the intestine. These
      results suggest that both intermediate TCR cells and IEL are generated as
      primitive T cells in phylogeny, but later develop along independent pathways at
      their respective sites.

PMID- 8287494
TI  - Appearance of extrathymic early differentiated CD4-CD8- T cells with T cell
      receptor gamma/delta or alpha/beta after thymus grafting to nude mice: influence
      of thymus on extrathymic T cell differentiation.
AB  - Fetal thymus grafting into athymic nude mice has been used as an experimental
      model of T cell development. To understand the early events of T cell
      development, we have examined the sequence of appearance of T cell subsets in
      lymph nodes (LN) of BALB/c nu/nu mice after grafting with syngeneic fetal thymus.
      T cells expressing T cell receptor (TCR) alpha/beta or gamma/delta increased in
      LN from 1 week after grafting, although no host-derived CD3+ T cells were
      detected in the grafted thymus and no donor thymus-derived T cells were detected
      in the LN. The early appearing T cells of both TCR alpha/beta and TCR gamma/delta
      showed a CD4-CD8- phenotype. V region usage analysis of the early appearing TCR
      alpha/beta T cells revealed that they contained cells bearing V beta 3 or V beta
      11, which are potentially reactive to self-superantigen Mls-2a or Dvb11,
      respectively, and are deleted in the course of T cell development in the thymus
      of euthymic BALB/c mice. The early appearing T cells showed neither mixed
      lymphocyte reaction nor cytotoxic T cell activity against allogeneic cells. In
      contrast, lymphokine-activated killer cells from early appearing T cells, which
      contained high percentages of TCR gamma/delta T cells, exhibited higher cytotoxic
      activity against P815 mastocytoma than those from euthymic mice or untreated nude
      mice. All these results suggest that the early appearing T cells are developed
      extrathymically. We propose that the thymus may induce extrathymic T cell
      development without direct cell-to-cell interaction. It seems likely that the
      extrathymically developed T cells, especially TCR gamma/delta T cells, induced by
      the thymus have some role in the defense mechanism in the absence of conventional
      thymus-derived T cells.

PMID- 8287495
TI  - 12-O-tetradecanoylphorbol 13-acetate stimulates human T-lymphocyte adherence to
      the fibronectin RGD domain and the laminin IKVAV domain.
AB  - In order for T cells to exit the circulatory system, these cells must attach to
      extracellular matrix proteins. We have used 12-O-tetradecanoylphorbol 13-acetate
      (TPA) to study the ability of human T cells to adhere to fibronectin or laminin
      or to specific domains on these extracellular matrix proteins. Both primary human
      T-lymphocytes and a T-cell line (H-9) adhered and spread well on solid-phase
      fibronectin and laminin in the presence of TPA, with maximum activity at 3 hr of
      treatment. Furthermore, attachment of both cell populations to fibronectin was
      inhibited using a soluble RGD-containing synthetic peptide or by pretreating the
      fibronectin with antibodies that block the RGD domain. A synthetic peptide from
      the CSI alternatively spliced region of fibronectin did not inhibit attachment to
      fibronectin. The H-9 cells also attached to the laminin A chain IKVAV-containing
      synthetic peptide, but not to the laminin-derived YIGSR- or RGD-containing
      sequences. Immunoprecipitation of 32P-labeled H-9 cells with antibodies to the
      beta 1 integrin subunit demonstrated phosphorylation of an alpha integrin subunit
      after treatment with TPA. These data demonstrate that TPA activates T-cell
      adherence to laminin and to fibronectin via specific sites on each protein and
      that this adhesion may be associated with integrin phosphorylation.

PMID- 8287496
TI  - Contraction of reconstituted Dictyostelium cytoskeletons: an apparent role for
      higher order associations among myosin filaments.
AB  - A large number of cellular functions require assembly of actin and myosin and
      coordinated interactions between the resulting filaments. To better understand
      the structure and function of one such contractile assembly, we have begun
      fractionation and reconstitution studies of Dictyostelium cytoskeletons. Isolated
      cytoskeletons rapidly contracted when mixed with Mg-ATP, and myosin II was
      essential for this since myosin-depleted (stripped) cytoskeletons failed to
      contract. Dictyostelium, Acanthamoeba, or skeletal muscle myosins bound to
      stripped cytoskeletons with equal efficiency, and the Mg-ATPase of all three
      myosins was stimulated by the cytoskeleton-associated actin. Near neutral pH,
      however, only the homologous system reconstituted with Dictyostelium myosin
      contracted, despite the fact that under the same conditions all three myosins
      bound to myosin-depleted (ghost) muscle myofibrils and restored contractility.
      Individual Dictyostelium myosin thick filaments have a strong tendency to
      aggregate and associate end-to-end, and this may be important for functional
      contraction of cytoskeletons. This suggestion is supported by the observation
      that under conditions where individual Acanthamoeba myosin filaments aggregated,
      reconstituted cytoskeletons contracted. None of the solution conditions tested
      caused rabbit muscle myosin filaments to aggregate or to contract cytoskeletons.
      Thus higher order associations among individual myosin filaments may be essential
      for some types of cell motility.

PMID- 8287497
TI  - Probing actin incorporation into myofibrils using Asp11 and His73 actin mutants.
AB  - We used a cell free system Bouche et al.: J. Cell Biol. 107:587-596, 1988] to
      study the incorporation of actin into myofibrils. We used alpha-skeletal muscle
      actin and actins with substitutions of either His73 [Solomon and Rubenstein: J.
      Biol.Chem. 262:11382, 1987], or Asp11 [Solomon et al.: J. Biol. Chem. 263:19662,
      1988]. Actins were translated in reticulocyte lysate and incubated with
      myofibrils. The incorporated wild type actin could be cross-linked into dimers
      using N,N'-1,4-phenylenebismaleimide (PBM), indicating that the incorporated
      actin is actually inserted into the thin filaments of the myofibril. The His73
      mutants incorporated to the same extent as wild type actin and was also cross
      linked with PBM. Although some of the Asp11 mutants co-assembled with carrier
      actin, only 1-3% of the Asp11 mutant actins incorporated after 2 min and did not
      increase after 2 hr. Roughly 17% of wild type actin incorporated after 2 min and
      31% after 2 hr. ATP increased the release of wild type actin from myofibrils, but
      did not increase the release of Asp11 mutants. We suggest that (1) the
      incorporation of wild type and His73 mutant actins was due to a physiological
      process whereas association of Asp11 mutants with myofibrils was non-specific,
      (2) the incorporation of wild type actin involved a rapid initial phase, followed
      by a slower phase, and (3) since some of the Asp11 mutants can co-assemble with
      wild type actin, the ability to self-assemble was not sufficient for
      incorporation into myofibrils. Thus, incorporation probably includes interaction
      between actin and a thin filament associated protein. We also showed that
      incorporation occurred at actin concentrations which would cause disassembly of F
      actin. Since the myofibrils did not show large scale disassembly but incorporated
      actin, filament stability and monomer incorporation are likely to be mediated by
      actin associated proteins of the myofibril.

PMID- 8287498
TI  - Rat liver fat-storing cell lines express sarcomeric myosin heavy chain mRNA and
      protein.
AB  - Fat-storing cells (FSC, lipocytes, or Ito cells) of liver store vitamin A and are
      the main producers of extracellular matrix in normal and cirrhotic liver. During
      liver injury, FSC undergo an activation process characterized by a decrease in
      vitamin A storage and an increase in cell proliferation and extracellular matrix
      deposition. This activation process also occurs upon culturing FSC from normal
      liver. In contrast to most cells of nonmuscle origin, activated FSC express two
      cytoskeletal proteins normally found in muscle, desmin, and smooth muscle alpha
      actin. Based on their strategic perisinusoidal location, it has been hypothesized
      that FSC play a role in regulating blood flow. However, the nature of the
      contractile elements involved in this process remains to be determined. In this
      communication we demonstrate the presence of a sarcomeric myosin in proteins
      solubilized from liver biomatrix. In addition we demonstrate the expression of
      sarcomeric myosin heavy chain (MHC) mRNA and protein in two FSC clones derived
      from a CCl4-cirrhotic rat liver (CFSC). Through cloning the cDNA corresponding to
      the MHC gene expressed in these cells we demonstrate that it encodes fast IId
      skeletal MHC and thus represents a marker normally seen in adult muscle. The
      unexpected expression of an adult stage skeletal muscle molecular motor in FSC
      from cirrhotic liver is consistent with the proposed specialized contractile
      capacity of these cells.

PMID- 8287499
TI  - Decreased levels of the high molecular weight subunit of neurofilaments and
      accelerated neurofilament transport during the recovery phase of 2,5-hexanedione
      exposure.
AB  - The neurotoxicant 2,5-hexanedione (HD) causes the accumulation of neurofilaments
      in the distal axon and an acceleration of neurofilament transport proximal to the
      site of their accumulation. It has been proposed that the acceleration of
      transport is due to the direct reaction of HD with neurofilament proteins and,
      conversely, that this acceleration is a secondary response to the axon to injury.
      The objective of this study was to determine whether the response of axons to HD
      intoxication includes acceleration of neurofilament transport. Pulse labelling
      was used to analyze neurofilament transport in age-matched rats exposed to HD or
      PBS. The animals receiving HD were exposed either throughout the period of
      radiolabel transport, or prior to the pulse labeling of neurofilament proteins.
      If acceleration of the rate of neurofilament transport was due to the direct
      reaction of HD with proteins, then neurofilaments synthesized after the exposure
      period should travel at control rates, since these proteins would not have been
      exposed to the toxicant. After 28 days of transport, optic nerve proteins were
      examined using SDS-PAGE, fluorography, and computerized densitometry. In both HD
      treated groups, neurofilament transport was accelerated relative to age-matched
      control animals. In addition, the amount of NFH was decreased relative to other
      neurofilament subunits. The combination of accelerated transport and a diminished
      proportion of NFH is similar to the observations of neurofilament axonal
      transport during growth and development. These observations suggest that this
      persistent, secondary effect is a reparative response to injury that
      recapitulates axonal growth and development.

PMID- 8287500
TI  - Microtubule sliding in reduced-amplitude bending waves of Ciona sperm flagella:
      resolution of metachronous and synchronous sliding components of stable bending
      waves.
AB  - Microtubule sliding associated with the bending of reactivated flagella of
      demembranated spermatozoa of the tunicate, Ciona, has been analyzed using a
      descriptive model that permits quantitation of metachronous and synchronous
      components of sliding. Reduced-amplitude bending waves, obtained by addition of
      increased salt (K acetate), lithium, or vanadate to the reactivation solutions,
      have been examined. Increased K acetate can decrease bend angle by as much as 70%
      with little change in frequency. In all cases, a decrease in the amplitude, or
      bend angle, of propagated bends is measured as a decrease in the metachronous
      component of sliding and is associated with a reduction in the growth of new
      bends after they begin to propagate during the second half-cycle of bend
      development. At higher K acetate concentrations, bend growth during the second
      half-cycle of bend development is very strongly reduced and may even become
      negative. A disparity between the rates of bend growth in the first and second
      half-cycles of bend development corresponds to a large amount of synchronous
      sliding in the distal portion of the flagellum. When the synchronous sliding
      component is large, the sliding velocity in a propagating bend decreases to near
      0 values and may even reverse its direction as the bend propagates through the
      mid-region of the flagellum. Since these large perturbations of sliding velocity
      do not interfere with regular propagation of bends with nearly constant bend
      angle, the bend propagation mechanism cannot operate by metachronous control of
      the velocity of sliding, and is unlikely to operate by local monitoring of either
      the amount or velocity of sliding. These observations therefore argue against
      models in which active sliding is regulated by shear or sliding velocity, and
      make curvature-controlled models relatively more attractive. In many cases, a
      reduction in sliding during bend initiation (the first half-cycle of development
      of new bends) also contributes to the decreased amplitude of propagated bends.
      These changes in bend initiation are similar in both full-length flagella and in
      flagella shortened by breakage. The amount of sliding that occurs during bend
      initiation is relatively independent of the distribution of sliding between
      metachronous and synchronous components in the distal part of the flagellum.
      These observations therefore provide additional evidence that bend initiation and
      bend propagation are independent and separable processes.

PMID- 8287501
TI  - Disorganization of microfilaments and intermediate filaments interferes with the
      assembly and stability of desmosomes in MDCK epithelial cells.
AB  - To investigate the possible role(s) of cytoskeletal elements in desmosome
      assembly we have studied the effects of cytostatic drugs on the assembly of
      desmosomes in MDCK epithelial cells. We showed previously [Pasdar et al.: Cell
      Motil. Cytoskeleton 23:201-213, 1992] that selective disruption of microtubules
      has no effect on desmosome assembly. Here, we have treated MDCK cells with
      cytochalasin B and a combination of cytochalasin B and nocodazole and analysed
      the effects of desmosome assembly. Immunofluorescence analysis of MDCK cultures
      following drug treatment indicated complete disruption of actin microfilaments
      and disorganization of cytokeratin intermediate filaments. Biochemical analysis
      of newly synthesized desmosomal membrane core glycoproteins as well as the cell
      adhesion protein E-cadherin revealed no effect of these drugs on the kinetics of
      synthesis, intracellular processing, or transport to the plasma membrane either
      in the presence or absence of cell-cell contact. However, morphological analyses
      revealed a significant disruption in the spatial organization of desmosomal
      proteins and E-cadherin. Drug treatment in the absence of cell-cell contact
      resulted in the disruption of the normally observed homogeneous punctate staining
      pattern and appearance of aggregate staining. Induction of cell-cell contact in
      these cultures resulted in redistribution of some of the aggregate staining to
      the plasma membrane. In contrast to control cultures, significant amount of
      intracellular staining was retained for all desmosomal proteins. Biochemical
      analyses of turnover rates of newly synthesized desmosomal proteins indicated a
      significant decrease in metabolic stability of these proteins while the turnover
      rate of E-cadherin was not significantly different among control and drug-treated
      cultures. Taken together, these results suggest that intact actin and cytokeratin
      filaments are necessary for the stability, efficient assembly, and spatial
      organization of the junctional components at the membrane. The regulatory role of
      cytokeratins and actin filaments in assembly and stability of desmosomes on the
      plasma membrane is discussed.

PMID- 8287502
TI  - Tales of a gypsy doc: perspectives on social and medical aspects of care of the
      American Gypsy population.

PMID- 8287503
TI  - Recurrence, remission, and relapse of seizures.
AB  - BACKGROUND: Approximately 6% of the population will experience at least one
      afebrile seizure in their lifetime. OBJECTIVE: To review the prognostic factors
      and clinical implications for recurrence, remission, and relapse of seizures.
      SUMMARY: Antiepileptic drug treatment reduces the risk of recurrence after a
      first seizure by about half, but these drugs cause a variety of adverse effects.
      The risk of recurrence is higher in the presence of neurologic or
      electroencephalographic abnormalities or if the seizure is partial as opposed to
      generalized. Neurologic abnormalities and partial seizures also reduce the
      probability of remission. Gradual drug withdrawal can be considered if the
      patient has been in remission for 2 years in the absence of any negative
      prognostic indicators. CONCLUSIONS: When deciding whether to begin or discontinue
      antiepileptic drug therapy, clinicians should consider the risks and possible
      benefits for the individual patient.

PMID- 8287504
TI  - Breaking the thrombolytic gridlock: insights from the GUSTO trial.

PMID- 8287505
TI  - Mortality of patients transferred to a tertiary care hospital.
AB  - BACKGROUND: Seriously ill patients are often transferred from community hospitals
      to tertiary care hospitals. OBJECTIVES: To review the numbers, sources, and
      outcomes of patients transferred to the Cleveland Clinic Hospital from 1989
      through 1992. METHODS: Retrospective analysis. RESULTS: Compared with the
      Cleveland Clinic's overall hospital mortality rate of 3.09% (3760 of 121,014
      patients) during this period, the mortality rate among transferred patients was
      8.26% (1092 of 13,226 patients). Although transferred patients accounted for only
      10.9% of the total admissions, they represented 29.0% of the deaths. Transfers
      from other hospitals in the Cleveland Health Quality Choice (HQC) program, a
      community-wide quality-assessment project, increased 40.2% in 1992 (during the
      initial data collection period for the HQC program), while those from non-HQC
      hospitals increased only 0.9%. CONCLUSIONS: Patients transferred to a tertiary
      care hospital from other acute care hospitals have a 2.7-fold greater chance of
      dying in the hospital than nontransferred patients. Public scrutiny of quality
      may increase the likelihood of transfer of seriously ill patients to tertiary
      care centers.

PMID- 8287506
TI  - Early-onset prosthetic valve endocarditis.
AB  - BACKGROUND: Endocarditis following cardiac valve implantation is a rare but
      serious complication. OBJECTIVE: To determine the risk and outcome of early-onset
      prosthetic valve endocarditis (EO-PVE) in adult patients at The Cleveland Clinic.
      METHODS: Retrospective review of a 5-year case series of patients who acquired
      bloodstream infections within 60 days of surgery identified through a prospective
      surveillance program. RESULTS: Sixty-eight of approximately 2100 patients
      acquired bloodstream infections; 16 (24%) contracted EO-PVE and 52 (76%) did not.
      Risk factors for EO-PVE included younger age, at least three sets of positive
      blood culture results, and an organism other than a gram-negative bacillus. The
      majority of patients with EO-PVE had a recognized source of infection (wound or
      vascular catheter site), but no infections were attributed to a pulmonary or
      urinary tract site. Eleven patients (69%) were cured, including six who underwent
      emergent second operations. CONCLUSION: Patients with multiple blood cultures
      positive for organisms other than gram-negative bacilli are at risk of EO-PVE,
      even when a primary wound infection or vascular catheter site infection is
      recognized and treated.

PMID- 8287507
TI  - Systemic diseases associated with intermediate uveitis.
AB  - BACKGROUND: Intermediate uveitis is characterized by vitreal inflammation with
      associated inflammation of the vitreous base and peripheral anterior retina and
      choroid. It may be found as an isolated and idiopathic condition or in
      association with systemic disorders such as multiple sclerosis and sarcoidosis.
      OBJECTIVE: To identify the clinical features of intermediate uveitis and assess
      its association with systemic diseases. METHODS: Retrospective study of 83
      patients presenting with intermediate uveitis between 1970 and 1991. RESULTS:
      Evidence of systemic disorders was found in 26 of 83 patients (31.3%). Of these
      26 patients, 10 had presumed sarcoidosis, 6 had multiple sclerosis, 2 had
      isolated optic neuritis, 2 had inflammatory bowel disease, 4 had isolated thyroid
      abnormalities, and 2 had histories suggestive of Epstein-Barr virus infection.
      Associated ocular findings included cystoid macular edema, peripheral retinal
      perivascular sheathing, cataracts, posterior vitreous detachment, fine keratic
      precipitates, preretinal macular fibrosis, retinal tears, retinal detachment, and
      optic disc edema. CONCLUSIONS: Patients with intermediate uveitis may have
      associated systemic diseases and should have careful follow-up with regular
      systemic evaluation.

PMID- 8287508
TI  - Hepatic toxicity of antirheumatic drugs.
AB  - BACKGROUND: Many of the diverse group of pharmacologic agents available for the
      treatment of rheumatic diseases have the potential to cause serious
      hepatotoxicity. OBJECTIVE: To identify factors associated with drug-induced
      hepatotoxicity in rheumatic disease. SUMMARY: While mild elevations in plasma
      transaminase concentrations are associated with almost all nonsteroidal anti
      inflammatory drugs (NSAIDs), clinically significant hepatic toxicity is very
      rare. NSAID-induced liver injury probably has an immunologic basis, but neither a
      detailed mechanism nor precise incidence rates are known. Methotrexate can cause
      hepatic fibrosis during chronic use, but the liver injury is poorly reflected by
      plasma transaminase concentrations; it is difficult to formulate monitoring
      recommendations when this agent is used in rheumatic disease. Gold and
      penicillamine have been associated with rare cases of hepatic toxicity as well.
      CONCLUSIONS: Drug treatment of rheumatic diseases is associated with a small but
      well-documented risk of hepatotoxicity. Recognizing the clinical syndromes
      associated with liver injury by these agents facilitates the minimization of
      morbidity from this complication.

PMID- 8287509
TI  - Associated ulcerative colitis, sclerosing cholangitis, and insulin-dependent
      diabetes mellitus.
AB  - We report two young men with clinical and laboratory evidence of macroscopic
      ulcerative colitis, sclerosing cholangitis, and insulin-dependent diabetes
      mellitus. The first patient presented at age 15 with vomiting, abdominal pain,
      weight loss, and abnormal liver function test results. Liver biopsy and
      endoscopic retrograde cholangiopancreatography (ERCP) demonstrated sclerosing
      cholangitis. Colonoscopy with biopsy revealed ulcerative colitis which responded
      to sulfasalazine. Diabetes occurred at age 18 and insulin therapy was begun. The
      second patient was 19 at presentation with diarrhea, hematochezia, and weight
      loss. Proctosigmoidoscopy revealed ulcerative colitis, and sulfasalazine led to
      clinical remission. Three months later he developed diabetes requiring insulin
      therapy. At age 28, he developed elevated alkaline phosphatase, and ERCP revealed
      sclerosing cholangitis. At age 37 he expired from adenocarcinoma that
      metastasized to the liver. Literature review revealed only one possible case
      report of this association with microscopic asymptomatic ulcerative colitis in
      that patient. Statistical analysis suggests that this association is real rather
      than a chance occurrence. An autoimmune process may be involved and a specific
      histocompatibility locus antigen (HLA) type may exert a regulatory influence.

PMID- 8287510
TI  - Acute noncardiogenic pulmonary edema due to polymer fume fever.
AB  - BACKGROUND: Certain fluorocarbon polymers can produce a clinical syndrome called
      polymer fume fever when the products of pyrolysis are inhaled. SUMMARY: A
      previously healthy 21-year-old white man presented with severe chest tightness,
      difficulty in breathing, pyrexia, nausea, vomiting, and a dry irritating cough.
      These symptoms occurred suddenly while smoking a cigarette 2 hours after leaving
      his place of work, where he is a plastics machinist. A chest roentgenogram
      revealed a bilateral patchy alveolar air space filling pattern involving the mid
      and lower lung fields. The diagnosis of polymer fume fever was established on the
      basis of the symptom complex, the association with cigarette smoking, and the
      occupational exposure to micronized polytetrafluoroethylene. CONCLUSIONS: A
      thorough occupational and smoking history is necessary to recognize polymer fume
      disease, which may resemble influenza.

PMID- 8287511
TI  - Which patients need aggressive lipid-altering therapy?

PMID- 8287512
TI  - Rheumatic manifestations of HIV infection.

PMID- 8287513
TI  - Dyspnea on exertion with cardiomegaly.

PMID- 8287514
TI  - Ability of two new thyrotropin (TSH) assays to separate hyperthyroid patients
      from euthyroid patients with low TSH.
AB  - We evaluated the ability of new thyrotropin (TSH) assays to separate hyperthyroid
      (n = 50) patients from clinically euthyroid subjects with low TSH values (nodular
      goiter, n = 20, and nonthyroidal illness, n = 22). Only patients whose serum TSH
      was < 0.1 mIU/L by immunoradiometric assay were included. We used a new
      immunofluorometric method based on time-resolved fluorescence (TR-IFMA) and a new
      immunochemiluminometric assay (ICMA) to measure TSH in serum. Although the
      differences between the hyperthyroid patients and the euthyroid patients differed
      from each other by both methods (P = 0.0012 for TR-IFMA and P < 0.0001 for ICMA),
      there was no cutoff point that could definitely separate the groups. Thus, it is
      not possible to draw any definite conclusions on whether a patient is
      hyperthyroid or not, solely on the basis of TSH concentration measured with these
      new TSH assays.

PMID- 8287515
TI  - Detection of simultaneous self-administration of testosterone and epitestosterone
      in healthy men.
AB  - Combined self-administration of testosterone (T) and epitestosterone (ET) by
      athletes counteracts the efficiency of the corresponding urinary glucuronides (G)
      ratio, (T/ET)G, as an indicator of T abuse. I therefore propose 5-androstene-3
      beta, 17 alpha-diol (5A3 beta 17 alpha), the immediate metabolic precursor of ET,
      as a new reference compound for the expression of relative excretions of T and
      ET. Thus (T/5A3 beta 17 alpha)G and (ET/5A3 beta 17 alpha)G become potential
      criteria to indicate joint administration of T and ET, since their respective
      threshold values (2.5 and 1.5) are exceeded even when (T/ET)G remains below the
      critical value of 6.

PMID- 8287516
TI  - Simplified isoelectric focusing/immunoblotting determination of apoprotein E
      phenotype.
AB  - We developed a rapid, accurate method for phenotyping apoprotein E that can be
      used for large-scale population studies. In this method, adapted from the method
      of Kamboh et al. (J Lipid Res 1988;29:1535-43), 10-microL plasma samples are
      incubated with dithiothreitol and Tween-20 for 15 min and then applied to 5%
      polyacrylamide gels containing ampholyte (pH 4.5-8) and urea (3 mol/L). After 2 h
      of isoelectric focusing, the apoprotein E bands are made visible by
      immunoblotting. Utilizing whole plasma, this method does not require time
      consuming ultracentrifugation, delipidation of samples, or dialysis. Small
      amounts of plasma are required, electrofocusing time is short, and as many as 160
      samples can be processed per day. Identification of phenotype is easily
      accomplished by noting the location and number of protein bands instead of their
      intensity. Because identification of phenotype is not affected by sialylation,
      neuraminidase treatment is not necessary. Agreement in identification of 301
      individuals from blinded duplicates was 96%, and there was 98% concordance of
      results for 431 samples that had undergone genetic typing. This method is thus
      well suited for large-scale population studies.

PMID- 8287517
TI  - Specificity of antigen assays of plasminogen activator inhibitor in plasma:
      Innotest PAI-1 immunoassay evaluated.
AB  - We evaluate a new commercial enzyme immunoassay (EIA) of plasminogen activator
      inhibitor-1 (PAI-1) in plasma, the Innotest PAI-1. Because we wanted to measure
      PAI-1 in blood samples, we developed a procedure for evaluating the specificity
      of the assay for different PAI-1 forms in their natural environment. All
      molecular forms were prepared from a plasma that contained only active PAI-1. The
      recovery of the different molecular forms of PAI-1, relative to active PAI-1
      (100%), was 99% +/- 7% for PAI-1 complexed with recombinant tissue-type
      plasminogen activator (t-PA), 104% +/- 4% for PAI-1 complexed with melanoma t-PA,
      94% +/- 11% for PAI-1 complexed with high-M(r) urokinase, and 113% +/- 3% for
      latent PAI-1. The parallelism between the calibration curve of the EIA and the
      serial dilutions of the different PAI-1 forms was considered acceptable for
      clinical purposes. In selected clinical plasma samples, the PAI-1 values obtained
      with the Innotest PAI-1 EIA correlated well with those of the TintElize PAI-1 EIA
      (r = 0.913, n = 106); the observed correlation of the Innotest measurements with
      PAI activity was r = 0.795 (n = 79). The Innotest PAI-1 antigen assay appears to
      detect all molecular forms of PAI-1 to a similar degree, and comes close to being
      the so-called grand total assay for detecting the total molecular concentration
      of PAI-1 in plasma.

PMID- 8287518
TI  - Total interleukin-6 in plasma measured by immunoassay.
AB  - Determinations of total cytokine concentration in biological fluids by
      immunoassays face two major problems: the biochemical heterogeneity of the
      analyte and the interference of cytokine-binding proteins. We developed an
      ultrasensitive enzyme immunoassay for interleukin-6 (IL-6), using monoclonal
      antibodies and acetylcholinesterase as the tracer enzyme. The antibodies
      recognized recombinant and glycosylated forms of IL-6 equally. The antibodies
      measured dimeric recombinant IL-6, yet we could not detect IL-6 oligomers in
      plasma samples. We investigated the potential interference of soluble IL-6
      receptor (sIL-6R), which is present at high concentrations in plasma samples (1
      to 2 nmol/L). Heat treatment of the sample obviated the sIL-6R interference.
      Using calibrators in a plasma matrix, we demonstrated by fractionation, dilution,
      and recovery experiments that the immunoassay accurately measured total IL-6 in
      both normal and pathological serum and plasma samples.

PMID- 8287519
TI  - StatPal II pH and Blood Gas Analysis System evaluated.
AB  - We evaluated a new portable instrument, the PPG StatPal II pH and Blood Gas
      Analysis System, designed for "point-of-care" measurements of blood gases and pH.
      Inaccuracy (% of target value) and imprecision (CV%) were assessed by blood
      tonometry and comparison with a Corning 178. Within-day results for PCO2
      inaccuracy and imprecision ranged from 98.2% to 102.9% and 3.3% to 3.9%,
      respectively; for PO2, these were 95.5% to 102.3% and 2.3% to 3.0%, respectively.
      Between-day results for PCO2 inaccuracy and imprecision ranged from 99.2% to
      99.3% and from 2.9% to 3.2%, respectively; for PO2, the ranges were 96.2% to
      98.2% and 2.6% to 3.0%, respectively. Two PCO2 outliers (in 645 samples = 0.3%)
      were observed. In general, tonometry recovery, measurement stability, and pH bias
      results for the StatPal II and Corning 178 were comparable. We conclude that the
      StatPal II performs within acceptable ranges of inaccuracy and imprecision.

PMID- 8287520
TI  - A step forward in enzymatic measurement of creatinine.
AB  - We describe an improved enzymatic ultraviolet absorbance method for assaying
      creatinine in serum, plasma, and urine. Creatinine is hydrolyzed by creatinine
      iminohydrolase (EC 3.5.4.21) to ammonia and N-methylhydantoin. The ammonia
      produced combines with 2-oxoglutarate and NADPH in the presence of glutamate
      dehydrogenase to yield glutamate and NADP+. The consumption of NADPH, measured by
      a two-point fixed-time assay, is proportional to the amount of creatinine in the
      sample. The assay is carried out in two steps: The first step eliminates
      background absorbance in hyperlipemic samples and endogenous ammonia through a
      "clearing system" and an isocitrate dehydrogenase-based "ammonia scavenger
      system"; the second step starts creatinine measurement. The method affords a
      simple, rapid, and sensitive assay with good precision and extended linearity; it
      employs working solutions stable at least 4 months. Test results compare closely
      with those of the isotope dilution-mass spectrometry Definitive Method, the HPLC
      procedure, and the fuller's earth method. The proposed method is not subject to
      interference from several metabolites or from the 72 drugs tested. Because it is
      easily automated, the method is suitable for routine work in clinical
      laboratories.

PMID- 8287521
TI  - Effect of calibration on dispersion of glycohemoglobin values determined by 111
      laboratories using 21 methods.
AB  - One hundred eleven laboratories, using 21 different methods based on five
      different principles, determined glycohemoglobin (GHb) percentages in two
      identical series of six lyophilized hemolysates and three similarly processed
      calibrators, distributed 3 months apart. To assign GHb percentages to
      calibrators, we used HbA1c results from nine participants who used the Bio-Rad
      Diamat high-performance liquid chromatographic method. Three-point calibration
      with assigned values improved mean intralaboratory variation (CV) from 6.6% to
      3.5%. For samples with low (5.5%) and high (14.1%) GHb percentages, respectively,
      calibration decreased interlaboratory variation per method (from 10% to 4% and
      from 6% to 3%), inter-method variation (from 18% to 4% and from 16% to 3%), and
      overall interlaboratory variation (from 25% to 7% and from 15% to 4%). Without
      calibration, 71% of the laboratories did not meet the clinically desirable
      intralaboratory CV of 3.5%; calibration reduced this proportion to 39%. We
      conclude that, irrespective of the analytical method used, calibration greatly
      reduces all sources of GHb variation.

PMID- 8287522
TI  - Rapid, sensitive fluorometric determination of serum triglyceride by measuring
      lipase-liberated fatty acids.
AB  - A continuous fluorescence displacement assay was developed for the measurement of
      long-chain fatty acids and utilized in the study of triglyceride lipase-catalyzed
      reactions (Wilton, DC. Biochem J 1991;276:129-33). We now describe a method for
      the rapid measurement of triglyceride in serum with the fluorescence displacement
      assay. The method involves the hydrolysis of a diluted sample equivalent to 0.1
      microL of original serum with excess lipase (EC 3.1.1.3) from Rhizopus arrhizus
      and measuring the fatty acid released after a set time interval, normally 1 min.
      Under the conditions of the timed assay, about 2 mol of fatty acid are released
      per mole of triglyceride. The released fatty acid is monitored by fluorescence
      change and is proportional to the concentration of triglyceride in the original
      serum sample. The effective range of serum triglyceride concentration that could
      be measured was 0.5-10 mmol/L (0.44-8.8 g/L), based on triolein standard. The
      assay is unique in that it measures lipase-liberated fatty acids rather than
      liberated glycerol and as such is not subject to many of the criticisms of the
      glycerol-based methods. Comparison of fasted serum samples established a high
      correlation between the fatty acid and glycerol methods.

PMID- 8287523
TI  - Improved fractionation of lipoproteins separated in microultracentrifuge tubes.

PMID- 8287524
TI  - Detection and identification of amphetamine and methamphetamine in urine by
      GC/MS.

PMID- 8287525
TI  - Two commercial automated immunoenzymometric assays for serum estradiol evaluated.

PMID- 8287526
TI  - A history of Bio-Science Laboratories.

PMID- 8287527
TI  - Increased lactate dehydrogenase isoenzyme-1 in a case of glucagonoma.

PMID- 8287528
TI  - Serum creatinine kinase MB after acute myocardial infarction in a patient with
      IgA-CK-BB complex.

PMID- 8287529
TI  - Confidence intervals in Clinical Chemistry.

PMID- 8287530
TI  - Reference values for androstanediol glucuronide.

PMID- 8287531
TI  - In vivo effects of neutrophil enzymes on cardiac enzymes.

PMID- 8287532
TI  - Improved sensitivity and precision of thyroid-stimulating hormone measurements by
      standardizing signal reagent addition in the Amerlite TSH 30 assay.

PMID- 8287533
TI  - Monoclonal gammopathies in Alzheimer disease.

PMID- 8287534
TI  - Kinetic error on Kodak Ektachem: a clue in diagnosis of myeloma.

PMID- 8287535
TI  - Desirable analytical quality specifications for clinical chemistry laboratories.

PMID- 8287536
TI  - Using relation between urinary cannabinoid and creatinine excretions to improve
      monitoring of abuser adherence to abstinence.

PMID- 8287537
TI  - Inhibition of the polymerase chain reaction by mucolytic agents.

PMID- 8287538
TI  - Association of low serum concentration of bilirubin with increased risk of
      coronary artery disease.
AB  - We examined serum bilirubin and various liver-function enzymes as possible risk
      factors for angiographically documented coronary artery disease (CAD). The
      studies involved a "training" set of 619 men for whom complete data on all risk
      factors considered were available, and a "test" set of 258 men for whom some risk
      factor data were not available. In both study groups, the liver enzymes were not
      related to CAD; however, In[total bilirubin] was inversely and statistically
      significantly related to the presence of CAD, both univariately and
      multivariately after adjustment for the established risk factors of age, total
      cholesterol, high-density lipoprotein cholesterol, smoking history, and systolic
      blood pressure. A 50% decrease in total bilirubin was associated with a 47%
      increase in the odds of being in a more severe CAD category. Our data suggest
      that serum bilirubin is an inverse and independent risk factor for CAD, with an
      association equivalent in degree to that of systolic blood pressure.

PMID- 8287539
TI  - Common and rare genotypes of human apolipoprotein E determined by specific
      restriction profiles of polymerase chain reaction-amplified DNA.
AB  - The three common isoforms of human apolipoprotein E (apo E) differ at positions
      112 and 158 and are named E3, E4, and E2 according to phenotyping by isoelectric
      focusing (IEF). The polymerase chain reaction (PCR) method allows the detection
      of common and several rare allelic apo E variants not detected by IEF. We propose
      a genotyping procedure for apo E that characterizes a given allele on the basis
      of amplification of specific sequences of the gene followed by the action of
      restriction endonucleases. When the nucleotide change does not lead to a
      restriction site, PCR-directed mutagenesis creates the discriminant site, and the
      differentiation of the three common alleles and five rare variants is possible.
      We present here profiles of common alleles and of three rare alleles, Weisgraber
      [Cys112/Asp127/Cys158], Christchurch [Cys112/Ser136/Arg158], and a new rare
      variant [Cys112/Leu142/Cys158].

PMID- 8287540
TI  - Two-site enzyme immunoassay of CD4 and CD8 molecules on the surface of T
      lymphocytes from healthy subjects and HIV-1-infected patients.
AB  - A highly sensitive two-site enzyme immunoassay (Capcellia) was developed to
      determine the concentration of CD4 and CD8 molecules expressed on the surface of
      human T lymphocytes. This assay, performed in one step (20 min), involves the
      specific immunocapture of T lymphocytes and reaction of the CD4 or CD8 molecules
      with an enzyme-labeled monoclonal antibody (mAb). The results were expressed as
      molar concentrations of the T-cell markers on the basis of results obtained with
      calibrated CD4 and CD8 standards. The assay was sensitive enough to detect 0.4
      pmol/L CD4 or 0.8 pmol/L CD8, which corresponded to approximately 20 x 10(6) CD4+
      or CD8+ T cells per liter of blood. Mean concentrations in healthy adults were
      17.2 pmol/L for CD4 and 22.1 pmol/L for CD8. The CD4 concentration was < 8 pmol/L
      in 50% of HIV-1-infected patients and in 95% of AIDS patients. Given the epitopic
      specificity of the mAb to CD4 we used, these values correspond to the
      concentration of CD4 molecules free of envelope glycoprotein (gp)120.

PMID- 8287541
TI  - Quantitative determination of CD4/CD8 molecules by a cell marker ELISA.
AB  - Determination of percentages of CD4+ and CD8+ T cells from patients with human
      immunodeficiency virus infection is usually done by flow cytometric analysis. We
      compared a cell marker ELISA with flow cytometry for quantitation of CD4 and CD8
      molecules on T lymphocytes, and correlated the values both with the number of
      CD4+ and CD8+ T lymphocytes and with clinical data. Results by cell marker ELISA
      (y) correlated well with those by flow cytometric analysis (x); r = 0.69, P <
      0.001 (y = 0.01x + 3.9) for CD4; r = 0.81, P < 0.001 (y = 0.03x + 5.4) for CD8; n
      = 343. The ELISA detected changes in numbers of CD8 molecules on the cells
      earlier than flow cytometry recognized changes in CD8+ T-cell counts. The
      advantages of the ELISA are the small sample volume required (0.5 mL of blood),
      its internal standardization by a CD4+/CD8+ cell line, and its simple and fast
      performance. The cell marker ELISA appears to be an efficient alternative to flow
      cytometry.

PMID- 8287542
TI  - Manipulation and flow of biological fluids in straight channels micromachined in
      silicon.
AB  - Analysis of minute sample volumes is a major analytical challenge that requires
      an understanding of fluid flow in microstructures. Accordingly, flow dynamics of
      biological fluids and cell suspensions in straight glass-capped silicon
      microchannels (40 to 150 microns wide, 20 and 40 microns deep) were studied. We
      demonstrated that these microstructures are appropriate components for
      microfluidic analytical devices. Different fluids were easily manipulated in the
      microchannels, and measurements of flow rate as a function of pressure for whole
      human blood, serum, plasma, and cell suspensions revealed non-Newtonian behavior.
      By means of micromachined filters (5 microns) located in channels, blood cells
      and microparticles were effectively separated from nanoliter-sized samples,
      clearly indicating the future role of microstructures for a variety of analytical
      purposes.

PMID- 8287543
TI  - Simultaneous determination of endogenous retinoic acid isomers and retinol in
      human plasma by isocratic normal-phase HPLC with ultraviolet detection.
AB  - We describe a rapid and simple procedure for the simultaneous quantitation of
      endogenous 13-cis-retinoic acid, all-trans-retinoic acid, and retinol by
      isocratic normal-phase HPLC with ultraviolet detection, in 0.5 mL of human
      plasma. A silica adsorption column was eluted with n-hexane:2-propanol:acetic
      acid (200:0.7:0.135 by vol) at 0.9 mL/min, and the effluent monitored at 350 nm.
      The arotinoid ethylsulfonic acid Ro 15-1570 was used as the internal standard.
      High sensitivity, allowing quantitation of physiological concentrations, was
      achieved, particularly for the retinoic acid isomers. The detection limits were
      0.5 microgram/L in plasma for both 13-cis- and trans-retinoic acid, and 10
      micrograms/L for retinol. The CVs for between-day determinations of the lowest
      quality-control concentration (n = 12) were 4.8% for 13-cis-retinoic acid, 3.4%
      for trans-retinoic acid, and 3.0% for retinol. The mean (+/- SD) concentrations
      of 13-cis-retinoic acid (1.79 +/- 0.56 microgram/L), trans-retinoic acid (1.35 +/
      0.42 microgram/L), and retinol (533 +/- 58 micrograms/L) measured in plasma from
      22 healthy volunteers agreed well with those previously reported.

PMID- 8287544
TI  - Analytical evaluation of Kone Microlyte determination of ionized magnesium.
AB  - We performed an analytical evaluation of a commercially available instrument for
      determining ionized magnesium through use of a neutral carrier, liquid-membrane
      based ion-selective electrode. Reproducibility (CV 2-4%), linearity (0.30-2.50
      mmol/L), lower limit of detection (0.30 mmol/L), and absence of interference from
      Ca2+ indicate adequate performance for measuring ionized magnesium in plasma or
      serum samples in the normal to high-concentration range. Sodium in excess of 150
      mmol/L caused a negative bias, which can be explained by ionic strength-induced
      changes in activity coefficients. The use of heparin as an anticoagulant must be
      restricted to concentrations < 15 units/mL because of the binding of magnesium to
      heparin. The mean +/- SD concentration of ionized magnesium and its fraction of
      total magnesium in 76 healthy volunteers were 0.56 +/- 0.05 mmol/L and 0.65 +/-
      0.04, respectively.

PMID- 8287545
TI  - Metabolic profiling of amniotic fluid by proton nuclear magnetic resonance
      spectroscopy: correlation with fetal maturation and other clinical variables.
AB  - Proton NMR spectroscopy at 600 MHz was performed on 70 specimens of human
      amniotic fluid, representing pregnancies at different stages of maturation and
      with different fetomaternal complications. Spectra with good signal-to-noise
      characteristics were obtained in 3.5 min of acquisition time, directly on
      untreated fluid, with presaturation to suppress the intense water resonance.
      Metabolites that generally gave rise to well-resolved resonances included
      lactate, glucose, creatinine, choline derivatives, citrate, acetate, alanine,
      glycine, glutamate, succinate, and others. For three of these metabolites-
      creatinine, glucose, and lactate--the peak intensities correlated well with
      results of conventional chemical analysis. The NMR spectra of third-trimester
      specimens were readily distinguishable from those of second-trimester specimens,
      and several peak intensities correlated with fetal maturation during the third
      trimester. Significant correlations with maternal preeclampsia and fetal open
      spina bifida were also observed.

PMID- 8287546
TI  - Concanavalin A-bound selenoprotein in human serum analyzed by graphite furnace
      atomic absorption spectrometry.
AB  - We developed an assay for the direct determination of selenium in serum with a
      Perkin-Elmer Model 4100ZL Zeeman atomic absorption spectrometer and Ag-Cu-Mg
      modifier. We used this assay to analyze concanavalin A-bound selenoprotein
      (CABSP) in human serum after concanavalin A (ConA) affinity chromatography. The
      CABSP was identified as a single-chain glycoprotein of 57.3 kDa. Carbohydrate
      units were N- and O-linked to the protein. The selenium moiety was
      selenocysteine. Total selenium, glutathione peroxidase (GPX; EC 1.11.1.9), ConA
      bound selenium (CABS), and alpha 1-acid glycoprotein (AAG) were determined in
      normal subjects and patients with various pathological conditions. CABS accounted
      for 44.1% +/- 6.3% of total selenium in sera from normal subjects and 46.5% +/-
      3.9% to 55.1% +/- 8.1% in sera from patients with a variety of diseases. Total
      selenium in serum was well correlated with serum CABS (r = 0.860), but not with
      serum GPX activity (r = 0.117), for all patients studied. Serum CABS increased in
      normal subjects after selenium supplementation. Serum CABSP did not behave as an
      acute-phase reactant, compared with AAG.

PMID- 8287547
TI  - Measurement of blood volume with an enriched stable isotope of chromium (53Cr)
      and isotope dilution by combined gas chromatography-mass spectrometry.
AB  - We used an established isotope dilution gas chromatography-mass spectrometry
      method to measure blood volumes with an enriched stable isotope of chromium. The
      results were compared with those of the conventional method, which involves
      radioactive 51Cr. The two methods were compared simultaneously in two male
      subjects of different sizes, and essentially identical volumes were obtained. The
      isotope dilution method is insensitive to contamination with natural (unenriched)
      chromium and can be used to measure all of the stable isotopes of chromium. The
      method has potential applications in simultaneous erythrocyte survival studies.
      The absence of radioactivity makes possible an accurate means of studying blood
      volume changes in children and during pregnancy.

PMID- 8287548
TI  - Time-resolved immunofluorometric assay of total renin in plasma and follicular
      fluid.
AB  - We developed a new time-resolved immunofluorometric assay (TR-IFMA) using two
      monoclonal antibodies for the total renin measurement in human plasma and
      follicular fluid. No conversion of prorenin to renin was needed because the assay
      detected both renin and prorenin. The detection limit of the assay was 10 ng/L
      and the linear range was 10-25,000 ng/L. Within-assay precision (CV) was 15-8% at
      renin concentrations of 50-12,200 ng/L. Between-assay precision was 19-3% at
      concentrations of 100-18,000 ng/L. Analytical recovery of added renin was 85-104%
      (n = 5) in plasma samples and 104-119% (n = 3) in follicular fluids. For plasma,
      the reference interval was 78-262 ng/L in men (n = 44) and 36-226 ng/L in women
      (n = 43).

PMID- 8287549
TI  - Radioimmunoassay of 2-hydroxyestrone in urine.
AB  - Catechol estrogens such as 2-OH estrone are interesting estrogen metabolites
      formed in several human tissues and excreted in urine. We developed and
      thoroughly validated a radioimmunoassay for urinary 2-OH estrone that has several
      advantages over published RIAs. Because we developed a relatively specific
      antiserum, we did not include a preliminary chromatographic step to eliminate
      cross-reacting urinary steroids. We hydrolyzed urinary steroid conjugates with
      beta-glucuronidase from Helix pomatia because recoveries after acid hydrolysis
      were only 49.6% compared with 73.8% after enzyme hydrolysis. Published RIAs for
      urinary 2-OH estrone use acid hydrolysis. Our RIA measured 2-OH estrone
      independently of the volume of sample, and the detection limit was between 100
      and 240 ng/L (10-24 pg per tube). The ED50 was 370 ng/L, and inter- and
      intraassay CVs for low, medium, and high concentrations were 22.5%, 22.8%, and
      19.9%, and 17.4%, 14.3%, and 10.8%, respectively. Median concentrations measured
      in 14 controls and 33 postmenopausal patients with breast cancer were 0.96 and
      1.55 micrograms/g creatinine, respectively, but there was considerable overlap
      between values from controls and patients.

PMID- 8287550
TI  - Is serum bilirubin a risk factor for coronary artery disease?

PMID- 8287551
TI  - Clinical significance of urinary cyclic guanosine monophosphate in diagnosis of
      heart failure.
AB  - We measured concentrations of guanosine 3',5'-monophosphate (cGMP) in plasma and
      urine of healthy subjects and patients with congestive heart failure, renal
      impairment, neoplastic disease, and hepatic cirrhosis. There was no correlation
      between cGMP concentrations in urine and in plasma. In all patients except those
      with renal impairment, urinary cGMP concentrations were significantly higher than
      in healthy persons. Only patients with heart failure or renal impairment showed
      significantly increased plasma cGMP concentrations. In contrast, cGMP in urine
      does not relate to the clinically assessed severity of heart failure (New York
      Heart Association functional classes). Determination of cGMP in plasma results in
      higher sensitivity and specificity for diagnosing heart failure than measurement
      of cGMP in urine.

PMID- 8287552
TI  - HPLC determination of oxidized and reduced pyridine coenzymes in human
      erythrocytes.
AB  - The nucleotide concentrations in acid and alkaline erythrocyte extracts have been
      measured by RP-HPLC in healthy controls and in patients bearing different
      inherited disorders, with altered erythrocyte NAD(P) levels. The objective was
      the simultaneous determination of the nucleotide profile and of the oxidative
      state of pyridine coenzymes by the most suitable extraction method. Both alkaline
      and acid extractions were necessary to obtain the complete pattern, due to
      defective recovery of the oxidized or reduced coenzymes, respectively, during the
      extraction procedures. Purine nucleotide quantification seemed to be reliable by
      all methods. High NADP+ levels were confirmed in two glucose-6-phosphate
      dehydrogenase deficient patients, coupled with raised NAD levels, lowered
      NADPH/NADP+ ratio and increased NADH/NAD+ ratio. Higher NAD+ and normal or lower
      NADH/NAD+ ratios were found in two hypoxanthine-phosphoribosyltransferase
      deficient patients, while a patient with superactive phosphoribosylpyrophosphate
      synthetase showed a decreased NADH level in addition to the low NAD+ level
      previously found.

PMID- 8287553
TI  - False rise in C-reactive protein in a patient with monoclonal IgM immunoglobulin.

PMID- 8287554
TI  - The glycosylation of haptoglobin in rheumatoid arthritis.

PMID- 8287555
TI  - Senile cataractic lenses do not accumulate galactitol in either lactose tolerant
      or intolerant subjects.

PMID- 8287556
TI  - Non-enzymatic glycosylation of mouse monoclonal antibody reduces its binding
      activity to antigen.

PMID- 8287557
TI  - Measurement of seminal plasma alpha-amylase that is not inhibited by monoclonal
      antibodies against the salivary isoenzyme.

PMID- 8287558
TI  - Urinary growth hormone measurements as a marker of renal tubular function in
      diabetes mellitus.
AB  - Urinary growth hormone (UGH) excretion was assessed in 44 adult subjects (10
      control, 21 insulin dependent diabetics (Group I), 13 diabetics in poor glycaemic
      control (Group II)). UGH was markedly elevated in the diabetic population. The
      UGH excretion in (1) control subjects ranged from undetectable levels to 0.7
      microU/h, mean 0.4, (2) Group I 73-422 microU/h, mean 250 and (3) Group II 10
      5,283 microU/h, mean 705. There was a significant correlation between UGH
      excretion and albumin excretion rate (AER) (r = 0.38, P < 0.05) in the subjects
      studied although only 50% of patients had an AER of > 20 micrograms/min. A
      stronger correlation was observed between beta 2-microglobulin and UGH excretion
      (r = 0.7, P < 0.01). There was no significant change in the 6-h serum GH levels
      following treatment in the patients in Group II. However a 23-79% decline in UGH
      excretion was observed following improvement of glycaemic control, although UGH
      levels failed to revert to normal. We conclude that the major factor responsible
      for increased UGH excretion in DM appears to be reduced tubular reabsorption of
      the hormone. This test may therefore prove useful as an additional marker for
      screening for diabetic nephropathy and may help in the understanding of the
      contribution of renal tubular abnormalities to the nephropathic process.

PMID- 8287559
TI  - A one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases
      2 using monoclonal antibodies.
AB  - A one-step sandwich enzyme immunoassay system was developed with a pair of
      monoclonal antibodies against two individual oligopeptides prepared from the
      amino acid sequence of the human tissue inhibitor of metalloproteinases-2 (TIMP
      2). The assay system consisting of two simultaneous immunoreactions used a solid
      phase monoclonal antibody and a horse-radish peroxidase-labeled monoclonal
      antibody. The system detected a free form of TIMP-2 and that complexed with
      active forms of matrix metalloproteinases (MMPs) giving a different sensitivity
      for each MMP but not TIMP-2 complexed with the precursor of 72 kDa
      gelatinase/type IV collagenase (MMP-2). The sensitivity of the system was 1.6
      microgram/l (16 pg/assay) and linearity was obtained between 6.3 and 50
      micrograms/l (63-500 pg/assay). TIMP-2 levels in the sera of 20 patients with
      rheumatoid arthritis (68 +/- 25 micrograms/l, mean +/- S.D.) and 13 patients with
      hepatocellular carcinoma (76 +/- 46 micrograms/l) were significantly higher (P <
      0.05) than those of 18 normal subjects (5.6 +/- 7.4 micrograms/l). In contrast,
      the levels in the sera of 10 patients with gastric cancer (45 +/- 18
      micrograms/l) and 7 patients with cancer of the uterus (36 +/- 13 micrograms/l)
      were significantly lower (P < 0.05 or P < 0.01) than those of normal subjects.
      Immunoreactivity analyses suggested that the precursor of MMP-2 in normal sera
      exists in a complexed form with TIMP-2 by interacting with the C-terminal domain
      of TIMP-2.

PMID- 8287560
TI  - Regulation of transferrin receptor expression and distribution in in vitro
      cultured human cytotrophoblasts.
AB  - During gestation the transplacental iron transport is very important to the
      fetus. Iron uptake by the placenta can be studied in cultured cytotrophoblasts.
      The influence of culture time and human differic transferrin on the number and
      distribution of transferrin receptors (TfRs) was investigated in human
      cytotrophoblasts. Cytotrophoblasts cultured for 2.5 h had few TfRs (0.28 pmol/mg
      protein). With time, total TfR amounts increase (4.14 pmol/mg protein at 70 h).
      They increase to a higher level in cells cultured in iron-poor medium, indicating
      that iron has an effect on the TfR synthesis/breakdown ratio. TfRs were
      distributed between two 'active' (located at the cell surface and
      intracellularly) and one 'inactive' (located intracellularly) receptor pools. TfR
      distribution among these pools was modulated by culture time and iron.
      Trophoblasts regulated iron uptake by variation of number of surface TfRs via
      changes in total TfRs and redistribution of TfRs among the receptor pools.

PMID- 8287561
TI  - Scintillation proximity assay for calcitriol in serum without high pressure
      liquid chromatography.
AB  - A rapid isolation step for 1,25-dihydroxyvitamin D3 without high pressure liquid
      chromatography (HPLC) and a sensitive radioimmunoassay (RIA) have been developed.
      The time required for extraction and isolation with a combination of Extrelut-1
      minicolumns and Sep-Pak silica cartridges from as little as 0.5 ml serum is only
      2 h. The assay can be counted after 8 h of incubation. It is performed in the
      vial that collects the eluate, thus eliminating transfer losses and errors. No
      separation of bound and free hormone is necessary before beta-counting in the
      scintillation proximity assay. The detection limit of the assay is 2.7 ng/l. The
      intra-assay coefficients of variation are 7.3% and 5.2% for samples with
      calcitriol concentrations of 31 and 148 ng/l, respectively. The inter-assay
      coefficients of variation are 11.3%, 13.3% and 16.1% for low (16 ng/l), medium
      (30 ng/l) and high (148 ng/l) control pool samples, respectively. Normal values
      for calcitriol range from 32 to 80 ng/l. Elderly subjects, patients with reduced
      kidney function and pregnant women were also evaluated for their calcitriol
      levels. This assay correlates well with a RIA employing HPLC prepurification and
      charcoal separation of bound/free calcitriol (r = 0.94).

PMID- 8287562
TI  - A fibroblast glutaryl-CoA dehydrogenase assay using detritiation of 3H-labelled
      glutaryl-CoA: application in the genotyping of the glutaryl-CoA dehydrogenase
      locus.
AB  - A method described earlier for measuring glutaryl-CoA dehydrogenase activity in
      fibroblasts has been further developed. This assay uses the detritiation of
      [2,3,4-3H]glutaryl-CoA both with and without added artificial electron acceptors
      as a measure of glutaryl-CoA dehydrogenase activity. Fibroblasts from patients
      with glutaryl-CoA dehydrogenase deficiency, as determined by the 14CO2 release
      assay, showed very low detritiation of [2,3,4-3H]glutaryl-CoA without added
      artificial electron acceptor. Obligate heterozgotes for glutaryl-CoA
      dehydrogenase deficiency showed detritiation activity intermediate between
      homozygotes and normal individuals. Addition of an electron acceptor to the assay
      mixture had no influence on the activity in homozygotes for glutaryl-CoA
      dehydrogenase deficiency but more than doubled the detritiation activity in
      obligate heterozygotes and in normal individuals. No difference in detritiation
      activity could be detected between glutaryl-CoA dehydrogenase deficient patients
      with a high urinary excretion of glutaric acid and patients with almost no
      excretion of glutaric acid. In all glutaryl-CoA dehydrogenase deficient cell
      lines tested the loss of decarboxylation activity was also accompanied by a loss
      of dehydrogenation activity. The detritiation assay was equivalent to, or even
      better than, the 14CO2 release assay in distinguishing between homozygotes and
      heterozygotes for glutaryl-CoA dehydrogenase deficiency.

PMID- 8287563
TI  - An improved Bradford protein assay for collagen proteins.
AB  - A modification of the protein determination method of Bradford adapted for
      collagen-rich samples is described. The use of Coomassie-based protein
      determination methods is limited by the great variation in colour yield obtained
      for different proteins. This is especially important in samples containing
      significant amounts of collagen where direct application of the methods of Lowry
      and Bradford results in underestimated values. Addition of small amounts of
      sodium dodecyl sulphate (SDS) (0.0035%) to the diluted solutions of Coomassie
      Brilliant Blue G used as dye reagent in the Bradford colorimetric assay caused a
      4-fold increase in the colour response of three collagen proteins (Col I, III and
      IV) and a decrease in absorbance for various non-collagen proteins. The presence
      of SDS in the reagent did not result in a significant metachromatic shift of the
      collagen-dye complexes. This simple modification in the preparation of the
      reagent for the Bradford assay allows similar response curves to be obtained for
      collagen and non-collagen proteins, making the modified assay of potential use
      for protein determination in collagen-rich samples such as pancreatic extracts.

PMID- 8287564
TI  - The effects of drugs on endocrine function.

PMID- 8287565
TI  - Pancreatic and islet transplantation for diabetes.

PMID- 8287566
TI  - Growth hormone replacement in adults: what dose?

PMID- 8287567
TI  - Short and long-term effects of growth hormone treatment on bone turnover and bone
      mineral content in adult growth hormone-deficient males.
AB  - OBJECTIVE: In view of the fact that GH-deficient adults present with pronounced
      osteopaenia and can be considered at risk for osteoporotic fractures, we wanted
      to investigate the effects of biosynthetic GH replacement therapy (0.25
      IU/kg/week) on biochemical indices of bone turnover and on bone mineral content
      (BMC) in a group of GH-deficient adult males. DESIGN: We performed a 6-month
      randomized, double-blind, placebo-controlled study, followed by 12-24 months of
      GH treatment in all patients. PATIENTS: Twenty adult males with GH deficiency of
      childhood onset were studied. MEASUREMENTS: We measured serum IGF-I, serum
      phosphate, biochemical indices of bone turnover (serum alkaline phosphatase
      activity, serum osteocalcin, serum carboxyterminal propeptide of type-I
      procollagen, fasting urinary hydroxyproline/creatinine and calcium/creatinine
      ratios) and bone mineral content, measured at the forearm and the lumbar spine by
      single and dual-photon absorptiometry respectively. RESULTS: After 3 and 6 months
      of GH administration, the serum levels of alkaline phosphatase, osteocalcin and
      carboxyterminal propeptide of type-I procollagen, and the fasting urinary
      hydroxyproline/creatinine ratio were significantly increased compared to placebo
      treated patients (P < 0.01 to P < 0.001). During the open study phase, the values
      for these indices of bone turnover remained elevated above pretreatment levels (P
      < 0.01 to P < 0.001 at 12 months), a downward trend becoming apparent after about
      one year of GH treatment. BMC values showed an initial decline after 3 months of
      GH treatment (most likely due to an expansion of the remodelling space), followed
      by a significant and progressive increase above pretreatment values, reaching
      7.8% for total BMC at the lumbar spine (L2-L4) and 9.9% for total BMC at the
      forearm, after 30 months of GH administration. CONCLUSIONS: The data of our study
      show that administration of substitutive doses of growth hormone to GH-deficient
      adult males activates bone turnover for a period of at least one year and
      suggests that this may have a beneficial effect on bone mass in these patients.

PMID- 8287568
TI  - Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of
      elderly men with low circulating IGF-I concentrations.
AB  - OBJECTIVE: We studied the relationship between plasma level of insulin-like
      growth hormone I (IGF-I), changes in lean body mass and in adipose mass, and
      adverse side-effects during human growth hormone (hGH) treatment of elderly men
      who had low IGF-I levels. DESIGN: The first six months was a period of baseline
      observation. The subjects were then randomized into two groups so that during
      months 7-18, men in group I received hGH, and men in group II served as untreated
      controls. SUBJECTS: Eighty-three overtly healthy elderly men, who were selected
      because their plasma IGF-I level was less than 0.35 units/ml. The men were
      randomly assigned in a ratio of three to one into group I (n = 62) or into group
      II (n = 21). MEASUREMENTS: Plasma IGF-I level was measured monthly. Lean body
      mass and adipose mass were measured every six months. RESULTS: Fifteen men left
      the study during the baseline period because of personal reasons or intercurrent
      medical events. In those who received drug (group I), there were a number of
      adverse reactions which could have been related to the hGH therapy: carpal tunnel
      syndrome 10, gynaecomastia 4, and hyperglycaemia 3. In total there were 27
      dropouts from group I and two dropouts from group II after the six-month point,
      for a variety of medical and non-medical reasons, the majority probably not
      related to hGH therapy. During the hGH treatment of group I, plasma IGF-I
      increased from the range 0.10-0.35 units/ml into the range 0.5-2.2 units/ml.
      Among the 18 men who completed 12 months of hGH treatment without experiencing
      one of the three above-noted presumed hGH side-effects, mean and peak plasma IGF
      I during treatment were significantly lower than among the 13 men who experienced
      carpal tunnel syndrome or gynaecomastia (one subject had both) while on hGH. With
      one exception, neither carpal tunnel syndrome nor gynaecomastia occurred in any
      individual with a mean IGF-I level less than 1.0 units/ml during hGH treatment.
      Twelve months of hGH treatment (group I) caused an increase in lean body mass to
      106% of the initial baseline (month one of the protocol), and a reduction in
      adipose mass to 84% of the baseline. Meanwhile, the lean body mass of the
      untreated men in group II declined to 97% of the initial baseline. The body
      composition responses after 12 months of treatment in group I were larger in the
      men whose mean intra-treatment IGF-I level was 0.5-1.0 units/ml, than in the men
      whose mean intra-treatment IGF-I level was 1.0-1.5 units/ml. CONCLUSIONS: These
      observations show that when elderly men with low circulating IGF-I concentrations
      are treated continuously with hGH, elevation of plasma IGF-I above 1.0 units/ml
      is associated with a substantial frequency of carpal tunnel syndrome or
      gynaecomastia. It may be that the effects of the hormone in expanding lean body
      mass and reducing adipose mass can be achieved, and the side-effects avoided, by
      maintaining the mean IGF-I level in the range 0.5-1.0 units/ml.

PMID- 8287569
TI  - Pituitary adenomas with high and low basal inositol phospholipid turnover; the
      stimulatory effect of kinins and an association with interleukin-6 secretion.
AB  - OBJECTIVE: We examined basal inositol phospholipid turnover and the response to
      the kinin, kallidin, in human pituitary adenomas and determined whether or not
      there was an association between these parameters and interleukin (IL-6)
      secretion status by the tumours. DESIGN: Pituitary adenoma tissue was dispersed
      and cells were cultured in monolayer for 96 hours. The medium was then removed
      and assayed for IL-6 and anterior pituitary hormones. The cells were labelled
      with 3H-myoinositol for 24 hours and then incubated under basal conditions with
      kallidin and, in some cases, with TRH and GnRH for 60 minutes. Total inositol
      phosphate accumulation and pituitary hormone secretion were assessed. PATIENTS:
      Tissue was collected from 29 consecutive patients being treated surgically for
      pituitary adenomas. MEASUREMENTS: Total 3H-inositol phosphates, growth hormone,
      prolactin, LH, FSH, TSH and immunoreactive IL-6. RESULTS: Two groups of pituitary
      adenomas were identified, one with high and one with low basal inositol
      phospholipid turnover. Kallidin stimulated inositol phosphate accumulation in
      seven of the 29 adenomas studied. The kallidin-responsive adenomas were
      associated with high basal phosphoinositide turnover. All seven kallidin
      responsive adenomas secreted IL-6. The adenomas studied with high basal inositol
      phosphate production were also responsive to TRH and in two tumours to GnRH.
      Kallidin stimulated GH release in one GH-secreting adenoma but had no effect on
      hormone secretion from any other tumour. CONCLUSION: Two groups of pituitary
      adenomas have been identified with high and low basal inositol phosphoinositide
      turnover. Phosphoinositide metabolism is readily stimulated by kallidin and TRH
      in adenomas with high but not low turnover. Kinin-responsive adenomas secreted IL
      6 but IL-6 secretor status does not preclude that they will respond to kallidin.

PMID- 8287570
TI  - The relationship between cortisol production rate and serial serum cortisol
      estimation in patients on medical therapy for Cushing's syndrome.
AB  - OBJECTIVE: The aim was to determine the target range into which mean daily serum
      cortisol should be lowered in patients on medical therapy for Cushing's syndrome,
      using isotopically estimated cortisol production rates as 'gold standard'.
      DESIGN: Patients with Cushing's syndrome on medical treatment were given 12 ng of
      tritiated cortisol intravenously and a 24-hour urine collection was made in a
      single day. On the same day, serum cortisol was measured at 0900, 1200, 1500,
      1800, 2100, and at 2400 h in in-patients. In addition, serum cortisol was
      measured at the same times as above in a group of healthy volunteers. SUBJECTS:
      Twenty-two patients on medical therapy for Cushing's syndrome were studied on a
      total of 29 occasions. In addition, serum cortisol profiles were obtained in 12
      healthy volunteers. RESULTS: The median serum cortisol in patients with Cushing's
      syndrome was 400 (range 66-839) nmol/l, and in the healthy volunteers 178 (range
      137-299) nmol/l. The median isotopic cortisol production rate in the patients
      with Cushing's syndrome was 84 mumol/24 h, range 10-343 (normal range 22-83)
      mumol/24 h. In the patients with Cushing's syndrome, the correlation of mean
      serum cortisol to cortisol production rate was +0.77 (P < 0.001). Normal rates
      were found when mean serum cortisol levels were between 150 and 300 nmol/l.
      CONCLUSIONS: The aim of drug therapy for Cushing's syndrome should be to lower
      the mean serum cortisol through the day into the range 150-300 nmol/l.

PMID- 8287571
TI  - Discrimination between beta-endorphin and beta-lipotrophin in human plasma using
      two-site immunoradiometric assays.
AB  - OBJECTIVE: We wished to discriminate between the opioid peptide beta-endorphin
      (beta-EP) and its non-opioid precursor beta-lipotrophin (beta-LPH) in normal
      subjects and patients with ACTH-related disorders. DESIGN: We produced monoclonal
      antibodies to beta-EP and beta-LPH for the development of two-site
      immunoradiometric assays (IRMAs) which specifically quantitate beta-EP and beta
      LPH. PATIENTS: Samples were obtained from patients with a range of ACTH-related
      disorders and compared with 18 normal subjects. Peptide levels were also compared
      in six patients with Cushing's syndrome undergoing bilateral inferior petrosal
      sinus sampling with corticotrophin releasing hormone administration.
      MEASUREMENTS: In the beta-EP IRMA, antibody 6B2, specific for beta-EP 18-27, is
      radiolabelled and antibody 2E10, recognizing beta-EP 1-5, is coupled to Sephacryl
      S-300 as solid phase. The IRMA is specific for beta-EP (beta-LPH cross-reacts <
      0.02%), has a detection limit of 1.4 +/- 0.7 pmol/l (n = 7) and has a within
      assay coefficient of variation of < 10% between 4.9 and 1200 pmol/l. In the beta
      LPH IRMA, antibody 6B2, which recognizes an epitope common to beta-LPH and beta
      EP, is radiolabelled and paired with solid-phase antibody 5C11 which recognizes
      beta-LPH 39-56. The binding site of this antibody ensures that beta-EP cannot be
      measured in the beta-LPH assay. The detection limit is 0.8 +/- 0.1 pmol/l (n = 9)
      and the within-assay coefficient of variation is < 10% at concentrations 1.7-870
      pmol/l. RESULTS: In normal subjects, beta-EP and beta-LPH levels were < 1.4-1.7
      pmol/l (< 5-6 ng/l) and 2.5-6.7 pmol/l (29-77 ng/l) at 0930 h and < 1.4-1.7
      pmol/l (< 5-6 ng/l) and 1.9-4.5 pmol/l (22-49 ng/l) at 1600 h, respectively. In
      patients with ACTH-related pathologies concentrations of beta-EP and beta-LPH
      paralleled those of ACTH. The ratio of beta-LPH:beta-EP in plasma varied between
      3.2:1 and 38:1 in these patients demonstrating that beta-LPH is the major
      circulating peptide derived from the C-terminal of pro-opiomelanocortin in man.
      However, in two patients undergoing bilateral inferior petrosal sampling with
      corticotrophin releasing hormone for diagnosis of Cushing's disease beta-EP
      concentrations increased rapidly during the first 5 minutes of the test,
      resulting in a sharp decrease in the beta-LPH: beta-EP ratio. These results
      suggest that beta-EP is preferentially released in response to acute
      corticotrophin releasing hormone stimulation. CONCLUSIONS: It is concluded that
      two-site IRMAs for beta-EP and beta-LPH provide an easy approach to study the
      dynamic changes in processing of beta-LPH to beta-EP.

PMID- 8287572
TI  - Thyroid dysfunction in African trypanosomiasis: a possible role for inflammatory
      cytokines.
AB  - OBJECTIVE: Sleeping sickness (African trypanosomiasis) is an anthropozoonosis
      transmitted by the tsetse fly. The treatments of choice are the antiparasitic
      agents suramin and/or melarsoprol. Experimental infection of animals with
      Trypanosoma brucei results in inflammatory lesions in the pituitary and/or the
      thyroid gland. In biochemical terms, these animals have hypothyroidism. We
      evaluated the functional integrity of the hypothalamic-pituitary-thyroid axis in
      patients with African trypanosomiasis before, during and after specific therapy.
      DESIGN: Prospective, controlled, cross-sectional study. PATIENTS AND
      MEASUREMENTS: Sixty-five patients with sleeping sickness (31 female, 34 male;
      aged 18-66; 32 with haemolymphatic sleeping sickness receiving suramin i.v., 33
      with cerebral sleeping sickness receiving melarsoprol) and 13 control subjects (6
      female, 7 male; aged 21-60) were enrolled in a cross-sectional study after giving
      informed consent. Fourteen patients were studied shortly after admission for
      sleeping sickness, 19 in the middle of the course of treatment, 18 at the end of
      the 5-week treatment period, and 14 patients after cure. All subjects underwent a
      TRH stimulation test at 1200 with bolus injection of 400 micrograms TRH i.v.
      Blood was drawn for determination of fT3, fT4, TSH, rT3, TNF-alpha, IL-1 and IL-6
      at 0 minutes and TSH at 60 minutes. All hormones and cytokines were determined by
      RIA or ELISA. RESULTS: Baseline TSH concentrations (mean +/- SEM) were elevated
      in unmedicated patients with sleeping sickness compared to normal subjects (2.6
      +/- 0.4 vs 1.4 +/- 0.2 mU/l; P = 0.01), whereas fT3 (2.7 +/- 0.5 vs 5.8 +/- 0.3
      pmol/l; P = 0.0002) and fT4 concentrations (10.3 +/- 1.2 vs 15.4 + 0.8 pmol/l; P
      = 0.007) were low. Stimulated TSH concentrations did not significantly differ
      from normal controls. Reverse T3 concentration in patients with sleeping sickness
      were normal (2.2 +/- 0.3 vs 2.4 +/- 0.2 nmol/l; P = NS). During the course of
      treatment, baseline TSH, fT3 and fT4 concentrations slowly returned to normal and
      were indistinguishable from controls after cure. Plasma concentrations of TNF
      alpha (16.0 +/- 4.1 vs 2.9 +/- 1.4 ng/l in controls; P = 0.003) and interleukin-6
      (19.2 +/- 7.3 vs 1.3 +/- 0.2 ng/l; P = 0.0001), but not interleukin-1 beta (2.0
      +/- 0.2 vs 0.9 +/- 0.2, ng/l P = NS), were elevated, when thyroid function
      impairment and disease activity were at their maximum, but gradually decreased
      into the normal range with therapy. We found a negative correlation between
      baseline cytokine concentrations and fT3 concentrations (TNF-alpha: r = -0.34, P
      = 0.003; IL-6: r = -0.43, P = 0.0001). CONCLUSIONS: We conclude that unmedicated
      sleeping sickness is associated with significant impairment of thyroid function,
      which is reversed with specific therapy. Elevated TSH concentrations and low fT3
      and fT4 concentrations suggest primary hypothyroidism in patients with sleeping
      sickness. However, an additional pituitary and/or hypothalamic component cannot
      be excluded. This impairment may be due to the elevated plasma cytokine
      concentrations found in these patients or may be the result of parasitic
      thyroiditis.

PMID- 8287573
TI  - Response of plasma low density lipoprotein subfractions to oestrogen replacement
      therapy following surgical menopause.
AB  - OBJECTIVE: Epidemiological studies suggest that postmenopausal oestrogen
      replacement reduces the incidence of cardiovascular disease. The purpose of this
      study was to establish the effects of oestrogen replacement therapy on
      subfractions of plasma low density lipoprotein in bilaterally oophorectomized
      women. DESIGN: In a placebo controlled, double-blind study, patients were
      randomized on a two to one basis to receive either oestradiol valerate (2 mg/day)
      or placebo respectively for a period of 16 weeks. PATIENTS: Seventeen women aged
      28-51 years who had all had hysterectomy and bilateral oophorectomy at least 2
      months before recruitment were assigned to either the active (n = 12) or placebo
      (n = 5) group. MEASUREMENTS: Plasma lipids, lipoproteins, apolipoproteins and LDL
      subfractions were determined immediately before and after the treatment period.
      LDL subfractions were isolated directly from plasma by density gradient
      ultracentrifugation within 24 hours. Non-parametric statistical analysis was
      carried out within each group using Wilcoxon's signed rank test for matched
      pairs. RESULTS: After 16 weeks of treatment, HDL cholesterol, apo A-I and HDL-2
      were increased in the group receiving oestrogen (HDL cholesterol +12%, P < 0.01;
      apo A-I +14%, P < 0.01; HDL-2 +24% P < 0.01). While there were no significant
      changes in serum cholesterol, LDL cholesterol or triglycerides, the proportion
      and concentration of the least dense LDL-I subfraction was decreased
      significantly (-27%, P < 0.05). The LDL subfraction of intermediate density (LDL
      II) was decreased in eight subjects, while small, dense LDL-III was unaffected.
      Overall, these changes resulted in an apparent shift in the distribution of LDL
      subfractions towards small, dense LDL-III, although there was no net increase in
      the latter. CONCLUSION: In view of a similar and characteristic response of LDL
      subfractions to hypolipidaemic drugs that enhance the clearance of LDL via the
      LDL receptor, the present findings suggest that oestrogen promotes the
      preferential removal of LDL-I and II by activating LDL receptors. As this effect
      is normally associated with a reduction in the circulating level of LDL, it
      should not be regarded as an unfavourable response to oestrogen replacement
      therapy.

PMID- 8287574
TI  - The determination of delta-5-androstenediol and its sulphate in serum and urine
      by gas chromatography-mass spectrometry.
AB  - OBJECTIVES: We developed an assay for delta-5-androstenediol (adiol) and delta-5
      androstenediol-3-sulphate (adiol-3S) in serum and adiol and total adiol sulphate
      (adiol-S) in urine. DESIGN: An analytical procedure using HPLC and gas
      chromatography-mass spectrometry was devised and tested for its reliability.
      MEASUREMENTS: After addition of deuterated androstenediol as internal standard,
      serum and urine samples were extracted. Steroid sulphates were hydrolysed. The
      extracts and hydrolysates were purified on HPLC, adiol was derivatized using
      heptafluorobutyric anhydride and finally quantified by gas chromatography-mass
      spectrometry. RESULTS: The assay is accurate and reproducible. The coefficient of
      variation (CV) for the determination of adiol in serum samples is 4% (intra
      assay) and 9% (interassay) and for urine samples 3 and 8% respectively. The intra
      assay CV for the adiol-3S analyses is 5% for serum and 2% for urine samples while
      the interassay CV values for adiol-3S are 10% for serum and 7% for urine samples.
      The recovery of adiol and adiol-3S from serum and urine samples is 97%.
      CONCLUSIONS: The developed assay meets the analytical demands needed for clinical
      applications.

PMID- 8287575
TI  - Delta-5-androstenediol and its sulphate in serum and urine of normal adults and
      patients with endocrine diseases.
AB  - OBJECTIVES: We evaluated the role of delta-5-androstenediol (adiol) and its
      sulphates in health and endocrine diseases. DESIGN: Serum and urine samples from
      healthy adult men and pre and post-menopausal women were analysed by gas
      chromatography-mass spectrometry to establish reference values. In patients who
      were either evaluated or treated for endocrine diseases, sequential serum samples
      were collected and analysed. PATIENTS: Reference values were obtained from 24
      healthy male, 23 premenopausal and 30 post-menopausal female volunteers. Adiol
      and delta-5-androstenediol-3-sulphate (adiol-3S) concentrations were determined
      in combination with other relevant steroids in patients with either pituitary (n
      = 5), adrenal (n = 2) or gonadal dysfunction (n = 1), or testicular carcinoma (n
      = 19). MEASUREMENTS: After addition of deuterated adiol as internal standard,
      serum and urine samples were extracted. Steroid sulphates were hydrolysed. The
      extracts and hydrolysates were purified on HPLC, adiol was derivatized and
      finally quantified by gas chromatography-mass spectrometry. RESULTS: The
      calculated reference ranges for adiol and adiol-3S concentrations in serum are
      respectively: in men 1.78-7.24 and 123-579 nmol/l, in premenopausal women 0.65
      6.93 and 21.2-298 nmol/l and in post-menopausal women 0.29-2.90 and 6.1-184
      nmol/l. Urinary values varied considerably. In the population with endocrine
      abnormalities serum adiol and adiol-3S concentrations were compared with other
      relevant steroids. CONCLUSIONS: The wide concentration range of adiol and adiol
      3S in urine makes analysis of these steroids in urine of little clinical value.
      Serum concentrations of adiol and adiol-3S are higher in men than in women.
      Premenopausal values are higher than post-menopausal. Adiol and adiol-3S in serum
      are significantly correlated in pre and post-menopausal women, r = 0.51 and r =
      0.69 respectively, but not in men. In endocrine patients the serum concentrations
      of adiol show an ACTH or LH dependency in women; adiol correlates with cortisol,
      dehydroepiandrosterone or androstenedione and, in males, additionally with
      testosterone. However, in several situations adiol correlates with none of these
      steroids. Although adiol secretion can be stimulated by ACTH and LH, the level of
      serum adiol is also determined by other factors. Finally, in adrenal carcinoma
      serum adiol and adiol-3S may be used as tumour markers.

PMID- 8287576
TI  - Combined 17 alpha-hydroxylase/17,20-lyase deficiency caused by heterozygous stop
      codons in the cytochrome P450 17 alpha-hydroxylase gene.
AB  - OBJECTIVE: To determine the genetic defect underlying congenital adrenal
      hyperplasia due to 17 alpha-hydroxylase deficiency in a genetic female. DESIGN:
      Blood samples were used as a source of genomic DNA. A library of size selected
      genomic DNA sequences was prepared. In addition, portions of the 17 alpha
      hydroxylase gene were amplified by the polymerase chain reaction and the gene
      products sequenced. PATIENTS: Samples were obtained from a patient with sexual
      infantilism, lack of secondary sexual characteristics and hypertension. Streak
      gonads were found on laparoscopy. RESULTS: Two point mutations were found, one in
      exon 3 and one in exon 4 which generate premature stop codons at codons 194 and
      239 in place of glutamate and arginine respectively. The mutation in exon 3 has
      not previously been reported in patients with 17 alpha-hydroxylase deficiency.
      CONCLUSION: The protein product of these defective genes could be expected to be
      severely truncated with no catalytic activity. This is in keeping with the
      complete lack of cortisol and sex steroid output in this patient. The polymerase
      chain reaction provides faster access to gene sequence information than previous
      procedures based on library screening prior to sequencing.

PMID- 8287577
TI  - Pregnancy associated osteoporosis.
AB  - OBJECTIVE: Previous literature reports have suggested that osteoporosis
      associated with pregnancy is a rare event. We have examined the prevalence of
      this condition and compiled data on the largest group of such patients in the
      literature. PATIENTS AND DESIGN: With the help of the National Osteoporosis
      Society 35 women with pregnancy associated osteoporosis were identified. These
      women were matched with a control group from our already established computer
      data bank for age, weight, height and calcium status. Detailed questionnaires
      were sent to the osteoporotic sufferers enquiring about their present condition,
      past medical and drug history, and their menstrual, lactational and obstetric
      histories. They were also asked to complete a detailed dietary history to
      establish their calcium status. A questionnaire was also completed by the parents
      of these women and the parents of the control group, asking specifically about
      fracture history. RESULTS: Twenty-nine women had idiopathic osteoporosis
      associated with pregnancy, while in six, the condition may have resulted from
      drug therapy or associated diseases. Pain occurring late in the first full term
      pregnancy was the most common presentation. The natural history was for the
      condition to improve with time. There was a significantly higher prevalence of
      adult related fractures (P < 0.02) occurring at an earlier age in the mothers of
      these women compared to a control population. CONCLUSION: We have identified 35
      women who have developed osteoporosis during or shortly after pregnancy and in
      only six of them could a recognized underlying cause be suggested. These findings
      would suggest that idiopathic osteoporosis associated with pregnancy may be more
      common than the current literature suggests. The higher prevalence of fractures
      in the mothers of our population compared to controls raises the question of a
      possible associated genetic factor in the aetiology of this condition.

PMID- 8287578
TI  - Direct in-vivo detection of atypical hormonal expression of a Sertoli-Leydig cell
      tumour following stimulation with human chorionic gonadotrophin.
AB  - A 60-year-old woman presented with progressive hirsutism and elevated serum
      testosterone levels. Selective bilateral ovarian and adrenal vein catheterization
      demonstrated mild elevated testosterone and androstenedione levels in the right
      ovarian vein, which increased considerably 15 minutes following intravenous
      injection of 5000 IU human chorionic gonadotrophin. Androgen levels decreased
      remarkably after administration of gonadotrophin hormone releasing hormone
      agonist (GnRH-a). On histological examination, diffuse stromal hyperplasia of
      both ovaries was noted, with a small Sertoli-Leydig cell tumour in the right
      ovary. This is the first report of preoperative, direct selective diagnosis of a
      small Sertoli-Leydig cell tumour with such a hormonal expression. Ovarian Sertoli
      Leydig cell tumours are rare sex cord stromal tumours that exhibit testicular
      like structure and differentiation. These tumours are potentially malignant, can
      cause progressive virilization (Young & Scully, 1985), and are often clinically
      manifested as palpable pelvic masses and virilization (Meldrum & Abraham, 1979;
      Friedman et al., 1985). We describe a patient with postmenopausal virilization
      due to Sertoli-Leydig cell tumour, in whom a remarkable increase in androgens was
      detected following intravenous human chorionic gonadotrophin injection, during
      adrenal and ovarian selective vein blood sampling. A remarkable decrease in the
      serum androgen level was noticed following an injection of gonadotrophin hormone
      releasing hormone-agonist (GnRH-a).

PMID- 8287579
TI  - Clinical implications of hyperinsulinaemia in women.
AB  - In the polycystic ovary syndrome, hyperinsulinaemia is commonly found in women
      with hirsutism, oligomenorrhoea and acanthosis nigricans and this subset of
      patients possess adverse risk factors for coronary artery disease, particularly
      reduced HDL2 concentrations. Conversely, raised serum insulin concentrations are
      not common in women with PCOS in whom raised serum LH concentrations or regular
      menstrual cycles are present. We postulate that both direct ovarian and indirect
      actions of insulin (through changes in IGFI-I, IGFBP-I and SHBG concentrations)
      play important roles in determining androgen concentrations in women. Many
      intriguing questions follow from this link between the control of nutrition and
      reproduction and many old observations required re-examination in this new light.
      Vital to our understanding in this field will be the cause of moderate
      hyperinsulinaemia, the action of insulin on the normal ovary, and the importance
      of adverse surrogate risk factors for heart disease in hyperinsulinaemic women.

PMID- 8287580
TI  - Differences in testosterone metabolism by beard and scalp hair follicle dermal
      papilla cells.
AB  - OBJECTIVE: Androgens have paradoxically different effects on hair follicles
      depending on body site, stimulating beard growth while inducing regression in
      some areas of the scalp. The mesenchyme derived dermal papilla at the base of the
      hair follicle regulates many aspects of the growth of follicular epithelium, and
      is probably the site of androgen action. Since 5 alpha-dihydrotestosterone is
      considered to be the active intracellular androgen in many target tissues and is
      required for some androgen-mediated hair growth, such androgen-sensitive cells
      should contain 5 alpha-reductase. This study was designed to investigate whether
      cultured human dermal papilla cells contain 5 alpha-reductase and whether the
      metabolic capacity varies with the body site of the follicle in line with the
      clinical picture. DESIGN: Testosterone metabolism in cultured dermal papilla
      cells from androgen sensitive beard follicles was compared with less androgen
      dependent non-balding scalp follicles. Primary cell cultures were established
      from follicles of 11 patients with normal hair growth. The cells were grown to
      confluence in 10-cm Petri dishes and incubated with 5 nM 3H-testosterone in serum
      free medium for 2 hours. The cells and the culture medium were collected
      separately for individual analysis. MEASUREMENTS: Unlabelled carrier and 14C
      marker steroids were added to both the cell and medium extracts before separation
      by thin-layer chromatography. The individual steroid identities were confirmed by
      recrystallizing up to five times to a constant 3H/14C ratio. RESULTS:
      Testosterone was taken up by both cell types; significant amounts of 5 alpha
      dihydrotestosterone were recovered inside beard cells, but not in scalp cells,
      whereas androstenedione was identified in both. An unidentified compound was
      present intracellularly in both cell types, but was not present in the culture
      medium. 5 alpha-Dihydrotestosterone was present only in the culture medium of
      beard cells but androstenedione was present in a similar amount in the medium
      from both cell types. The presence of other steroids could not be confirmed in
      either the cell extracts or the culture medium. CONCLUSIONS: The production of 5
      alpha-dihydrotestosterone by beard cells concurs with the poor beard growth in
      men with 5 alpha-reductase deficiency, supporting our hypothesis that androgens
      mediate their effects on the hair follicle via the mesenchyme-derived dermal
      papilla.

PMID- 8287581
TI  - Alternate-day GnRH therapy for ovarian hypofunction induced by weight loss:
      treatment of six patients who remained amenorrhoeic after weight gain.
AB  - OBJECTIVE: Body weight loss has an adverse effect on the pituitary-ovarian
      function, and no restoration of the function occurs in 20-30% of patients even
      after the recovery of body weight. In the present study, the efficacy of
      alternate-day GnRH therapy was investigated in six patients whose pituitary
      ovarian function had not recovered at 15 months to 6 years after the recovery of
      body weight. DESIGN: Synthetic GnRH (100 micrograms) was injected intramuscularly
      on alternate days for a total of 12 doses. On the completion of GnRH
      administration the efficacy of clomiphene-human chorionic gonadotrophin (hCG)
      therapy was evaluated. A GnRH loading test and evaluation of LH secretion
      patterns were also performed to investigate the changes in hypothalamic-pituitary
      ovarian function secondary to GnRH treatment. RESULTS: All six patients ovulated
      in response to clomiphene-hCG therapy after 1-3 courses of GnRH treatment. The
      ovulatory response to clomiphene-hCG continued during follow-up periods of 5
      months to 5 years. The initial hormonal change induced by GnRH treatment was a
      rise in the basal serum FSH level and a return of the FSH response to GnRH
      loading. This was followed by an increase in serum LH and the return of LH
      response to GnRH loading. In all six patients, pulsatile LH secretion was absent
      before starting GnRH treatment. GnRH treatment produced LH pulses in five of the
      six patients, although the pulse frequency was less than that in normally cycling
      women. A further increase in the pulse frequency was observed during clomiphene
      therapy. CONCLUSIONS: Alternate-day GnRH administration is effective in inducing
      responsiveness to clomiphene in patients with anovulation secondary to weight
      loss.

PMID- 8287582
TI  - Effects of norethisterone on bone related biochemical variables and forearm bone
      mineral in post-menopausal osteoporosis.
AB  - OBJECTIVE: Progestogens may be a useful therapeutic alternative to oestrogen in
      the treatment of post-menopausal osteoporosis. The purpose of this study was to
      determine the effects of norethisterone on forearm bone mineral content and bone
      related biochemical variables in patients with post-menopausal osteoporosis.
      DESIGN/PATIENTS: The effects of treatment with norethisterone (5 mg/day) on bone
      related biochemical variables was determined in 44 women with post-menopausal
      osteoporosis. The effects of norethisterone on forearm bone mineral content (FMC)
      were evaluated by serial measurements in 39 of these women. MEASUREMENTS: We
      measured forearm mineral content, forearm mineral density, forearm fat content
      and fat-corrected forearm mineral density. Biochemical measurements included
      plasma calcium and plasma calcium fractions (ionized, protein bound, complexed
      and ultrafiltrable), alkaline phosphatase, bicarbonate, phosphate, albumin and
      globulins, serum parathyroid hormone, osteocalcin and 1,25-dihydroxyvitamin D,
      radiocalcium (45Ca) absorption and fasting urinary calcium/creatinine,
      sodium/creatinine, phosphate/creatinine and hydroxyproline/creatinine molar
      ratios. RESULTS: After 4 months of treatment norethisterone produced a fall in
      plasma calcium (mean +/- SEM from 2.40 +/- 0.14 to 2.32 +/- 0.13 mmol/l, P <
      0.001), primarily in the non-ionized calcium, due to a decrease in plasma
      bicarbonate (from 29 +/- 0.28 to 27 +/- 0.28 mmol/l, P < 0.001). There were
      decreases in urinary calcium/creatinine (from 0.41 +/- 0.03 to 0.19 +/- 0.02, P <
      0.01) and sodium/creatinine (from 15 +/- 1.1 to 10 +/- 0.93, P < 0.001) molar
      ratios and a rise in the renal tubular maximum for calcium reabsorption (TmCa)
      (from 2.36 +/- 0.041 to 2.55 +/- 0.059 mmol/l of glomerular filtrate, P < 0.001).
      Plasma phosphate, urinary phosphate/creatinine and tubular maximum for phosphate
      reabsorption (TMP) all fell (P < 0.01). Both the urinary
      hydroxyproline/creatinine (P < 0.001) and plasma alkaline phosphatase (P < 0.001)
      fell. Serum parathyroid hormone rose from 4.1 +/- 0.36 to 5.5 +/- 0.51 pmol/l (P
      < 0.02) and radiocalcium absorption increased from 0.67 +/- 0.08 to 0.81 +/- 0.10
      fx/h (P < 0.01). There was no change in serum 1,25-dihydroxy vitamin D. After
      treatment with norethisterone for 4 months there was an increase in forearm bone
      mineral content (P < 0.05) and a decrease in forearm fat content (P < 0.02).
      After two years treatment with norethisterone fat-corrected forearm bone mineral
      content rose (mean change 17.0 +/- 5.5 mg/cm, P < 0.01). CONCLUSIONS: These
      results suggest that norethisterone prevents bone loss in post-menopausal
      osteoporosis by decreasing bone turnover, has a vitamin-D independent effect on
      intestinal calcium absorption, and increases serum parathyroid hormone levels.

PMID- 8287583
TI  - Reversibility of thyroid dysfunction induced by recombinant alpha interferon in
      chronic hepatitis C.
AB  - OBJECTIVE: Thyroid dysfunction has been reported as a complication of interferon
      therapy. The aim of our study was to assess the risk factors and reversibility of
      thyroid disorders induced by interferon therapy. DESIGN: Prospective study.
      PATIENTS: A series of 68 patients with chronic hepatitis C completed a
      therapeutic trial of interferon alpha 2b (IFN), randomized for dose adaptation,
      lasting for 24 weeks. MEASUREMENTS: TSH and autoantibodies against thyroid were
      looked for at (-2) weeks and 24 weeks in all patients. Blood samples obtained at
      (-2), 12, and 24 weeks were stored for additional hormonal studies in patients
      who developed thyroid dysfunction. Such patients with thyroid dysfunction were
      followed up for at least one year. RESULTS: Only one out of 68 patients had
      abnormal TSH levels, and two had thyroid autoantibodies prior to interferon
      therapy. Eight patients (12%) developed thyroid dysfunction (five hypothyroidism
      and three hyperthyroidism) during treatment. In four patients (all of them with
      thyroid dysfunction, P < 0.001) antimicrosomal, antithyroglobulin, and/or anti
      TSH receptor antibodies appeared during interferon therapy. All patients
      recovered normal thyroid function within 1.5 years after interferon withdrawal.
      No pretreatment risk factor was identified. The patients with thyroid dysfunction
      did not significantly differ from the others as regards the dose of interferon
      they received or the rate of normalization of transaminases. CONCLUSION: (i) A
      12% incidence of thyroid dysfunction was observed under interferon therapy; (ii)
      secondary appearance under interferon therapy of elevated thyroid autoantibodies
      was a risk factor; (iii) the thyroid disorders induced by interferon were
      reversible.

PMID- 8287584
TI  - Tissue resistance to 1,25-dihydroxyvitamin D without a mutation of the vitamin D
      receptor gene.
AB  - OBJECTIVE: Hereditary vitamin D resistant rickets (HVDRR) is characterized by
      severe rickets and is often accompanied by alopecia. Mutations in the gene
      encoding the vitamin D receptor have been found in this condition. In a patient
      with the characteristic phenotype we have investigated the functional defect and
      sequenced the gene to seek a mutation. DESIGN: Patient and control cell lines
      prepared from skin fibroblasts and peripheral blood lymphocytes were used to
      measure binding of 1,25(OH)2D3 and to isolate vitamin D receptor mRNA. VDR cDNA
      was sequenced and transfected into receptor defective cells. PATIENT: A child
      with alopecia diagnosed as having rickets due to resistance to 1,25(OH)2D3.
      MEASUREMENTS: Cytosolic binding and nuclear association of 1,25(OH)2D3 were
      determined in patient and control cells, and functional response to 1,25(OH)2D3
      assessed by measurement of 24-hydroxylase activity. VDR mRNA was prepared,
      reverse transcribed, and cDNA sequenced. VDR cDNA was also transfected into VDR
      deficient CV-1 cells and functional response to 1,25(OH)2D3 assessed by co
      transfection with a chloramphenicol acetyltransferase (CAT) reporter plasmid.
      RESULTS: VDR from the patient were able to bind 1,25(OH)2D3 but showed no nuclear
      localization resulting in an absence of functional response to 1,25(OH)2D3.
      Sequencing revealed that the VDR coding region was normal. Expression studies of
      the patient's VDR showed functionally normal VDR as evidenced by normal
      transactivation in the presence of 1,25(OH)2D3. CONCLUSION: These data indicate a
      new cause of tissue resistance to 1,25(OH)2D3 which occurs in the absence of
      mutations in the coding region of VDR gene and which is characterized by
      defective nuclear localization of this receptor.

PMID- 8287585
TI  - The effect of morphine and naloxone administration on maternal oxytocin
      concentration in late pregnancy.
AB  - OBJECTIVE: Modification of the inhibitory control of oxytocin secretion by
      endogenous opiates in late pregnancy may be one of the factors involved in the
      onset of labour. The interrelationships between exogenously administered opioids
      and oxytocin may demonstrate activity of this control mechanism. This study was
      undertaken to investigate the effect of an opiate and an opiate antagonist on
      maternal oxytocin levels in late pregnancy. DESIGN: Patients were randomized to
      receive either morphine (5 mg), naloxone (2.4 mg) or sterile water (1 ml)
      intravenously. PATIENTS: Thirty women with singleton pregnancies greater than 36
      weeks gestation who were not in labour were studied. MEASUREMENTS: Blood for
      peripheral oxytocin levels was sampled every 2.5 minutes for 15 minutes before
      and 15 minutes after administration of the assigned substance. Oxytoxin was
      measured by radioimmunoassay. Peripheral beta-endorphin levels were measured at
      the beginning and end of the study. RESULTS: There was no significant change in
      the maternal oxytocin concentration after administration of either morphine,
      naloxone or sterile water compared to pretreatment levels. beta-Endorphin levels
      did not change significantly, either from the beginning to the end of the study,
      or between groups. CONCLUSION: In late pregnancy exogenous opiates and opiate
      antagonists have no effect on maternal peripheral oxytocin levels.

PMID- 8287586
TI  - Recombinant human growth hormone therapy does not increase microalbuminuria in
      children with short stature.
AB  - OBJECTIVE: Concerns have been raised about possible adverse effects of growth
      hormone on renal function. We measured microalbuminuria as a sensitive index of
      early glomerular damage in children being treated with recombinant human growth
      hormone. DESIGN AND PATIENTS: Microalbuminuria was measured in a group of 17
      children with short stature being treated with recombinant human growth hormone
      and in a group of 13 patients with idiopathic short stature not receiving
      therapy. MEASUREMENTS: Microalbuminuria was measured by a commercially available
      ELISA and urinary creatinines were determined using a Beckman creatinine
      analyser. RESULTS: The level of microalbuminuria was 0.484 +/- 0.275 g
      albumin/mol creatinine (mean +/- SD) in the patients receiving growth hormone and
      0.681 +/- 0.574 g albumin/mol creatinine in the untreated controls. There was no
      statistically significant difference between these values. CONCLUSIONS: Treatment
      with recombinant human growth hormone does not cause an increase in
      microalbuminuria in children with normal renal function. This supports the safety
      of this medication in growth hormone deficient children with normal renal
      function.

PMID- 8287587
TI  - Preliminary observations using endocrine markers of pituitary venous dilution
      during bilateral simultaneous inferior petrosal sinus catheterization in
      Cushing's syndrome: is combined CRF and TRH stimulation of value?
AB  - OBJECTIVE: We determined whether the measurement of hormones in pituitary blood
      permits correction for dilution by non-pituitary blood during bilateral
      simultaneous inferior petrosal sinus blood sampling in Cushing's syndrome.
      DESIGN: Bilateral simultaneous inferior petrosal sinus blood sampling was
      performed after combined hCRF and TRH stimulation. Peak ACTH concentrations were
      corrected for the TSH and PRL inter-sinus ratio, assuming uniform secretion of
      both hormones into each inferior petrosal sinus. PATIENTS: Eight patients with
      clinical and biochemical features of Cushing's syndrome. MEASUREMENTS: Basal and
      stimulated ACTH, TSH and PRL concentrations were measured after bilateral
      simultaneous inferior petrosal sinus blood sampling and simultaneously from a
      peripheral forearm vein. RESULTS: Basal central:peripheral ACTH ratio
      misdiagnosed four of eight patients as having non-pituitary disease. Peak
      uncorrected ACTH central:peripheral ratio erroneously suggested two of eight
      patients had non-pituitary disease. ACTH central:peripheral ratio corrected by
      TSH and PRL correctly predicted pituitary-dependent disease in all eight cases
      and provided correct lateralization data in four of five patients with a
      unilateral pituitary microadenoma. CONCLUSION: This study suggests that measuring
      other hormones in pituitary blood after TRH stimulation can offer a simple and
      reliable method for correcting for dilution by non-pituitary blood during
      bilateral simultaneous inferior petrosal sinus blood sampling in Cushing's
      syndrome.

PMID- 8287588
TI  - Modulation of IGF-I receptors by exogenous hGH treatment in constitutionally
      short children.
AB  - OBJECTIVE: To study the in-vivo regulation of IGF-I binding sites on erythrocytes
      (RBC) following administration of growth hormone (hGH) to constitutionally short
      children. Recently, owing to biosynthetic techniques, treatment with hGH has been
      administered not only to children with GH deficiency but also to children with
      constitutional growth delay and with familial short stature. PATIENTS AND DESIGN:
      Growth hormone (rhGH-Norditropin, Novo/Nordisk) was administered at a dose of 0.1
      U/kg/day s.c. to 11 children with constitutional short stature. Before and at 1-2
      months after initiation of treatment IGF-I binding sites and serum IGF-I were
      determined. Erythrocytes were separated from whole blood by centrifugation over
      Ficoll Hypaque and used to assess IGF-I binding sites. RESULTS: Serum IGF-I
      levels increased from 14.93 +/- 1.50 nmol/l (mean +/- SEM) to 30.29 +/- 2.32
      nmol/l, with a mean difference of 15.36 +/- 2.21 (P = 0.00001). Concomitantly,
      the number of binding sites per cell decreased from 5.77 +/- 0.81 sites per cell
      (m +/- SEM) to 2.10 +/- 0.36, with a mean difference of -3.67 +/- 0.76 (P =
      0.0003). The dissociation constant (Kd) also decreased from 0.47 +/- 0.16 nM (m
      +/- SEM) to 0.10 +/- 0.02 with a mean difference of -0.37 +/- 0.16 (P = 0.02),
      indicating an increase in the affinity of the receptors. CONCLUSION: Treatment of
      children with constitutional short stature with hGH raises the circulating IGF-I
      levels and down-regulates the IGF-I receptors. This study shows that IGF-I is
      capable of regulating its homologous receptor concentrations in vivo and it is
      suggested that the measurement of IGF-I binding sites on RBC may be used for the
      diagnosis of subtle states of resistance to IGF-I.

PMID- 8287589
TI  - Hypercalcaemia due to parathyroid hormone-related protein: long-term circulating
      levels may not reflect tumour activity.
AB  - Parathyroid hormone-related protein is responsible for the hypercalcaemia caused
      by many tumours. Measurement of parathyroid hormone-related protein is becoming
      more accessible with the introduction of commercial assays. We report a case of
      hypercalcaemia of malignancy secondary to parathyroid hormone-related protein in
      a woman with renal carcinoma. The parathyroid hormone-related protein was assayed
      using a new immunoradiometric assay. We demonstrated an initial fall in
      parathyroid hormone-related protein and calcium levels after surgery and a rise
      in both before clinical relapse. However, the clinical relapse was itself
      associated with a fall in serum parathyroid hormone-related protein, nephrogenous
      cAMP and calcium, suggesting that the tumour had stopped producing parathyroid
      hormone-related protein or perhaps that post-translational processing had
      occurred as the tumour advanced. The tumour was investigated for parathyroid
      hormone-related protein mRNA content using reverse transcriptase polymerase chain
      reaction, both at diagnosis in surgically removed material, and using post-mortem
      specimens. The level of parathyroid hormone-related protein mRNA, while present,
      was much reduced in the recurrent tumour suggesting that active parathyroid
      hormone-related protein production fell substantially as the tumour advanced.
      This case suggests that, although demonstration of parathyroid hormone-related
      protein in hypercalcaemia is useful for diagnosis, tumoral secretion of this
      product may alter.

PMID- 8287590
TI  - Transsphenoidal resection in Cushing's disease: definition of success.

PMID- 8287591
TI  - Germ-line transcripts and class switching.

PMID- 8287592
TI  - Failure in IgA secretion by surface IgA-positive B cells in common variable
      immunodeficiency (CVID).
AB  - CVID is an acquired disease with low serum immunoglobulins. Patients are
      classified into three groups on the ability of their B cells to secrete IgM and
      IgG in vitro in response to IL-2. We have now extended this patient
      classification to include IgA secretion and to assess whether the patients have
      IgA+ B cells in the circulation. B cells from almost all of the CVID patients
      studied were unable to secrete any IgA in vitro, with or without IL-2, although
      all B cells tested from normal donors showed some spontaneous IgA secretion.
      Thus, the defect with IgA secretion is more profound than with the secretion of
      IgM or IgG. Despite this failure to secrete IgA, using flow cytometry techniques
      all CVID patients tested were found to have IgA+ cells (expressed as a percentage
      of B cells) within the normal range. This suggests that CVID may involve a defect
      in the secretion of immunoglobulin isotypes rather than a defect in isotype
      switching.

PMID- 8287593
TI  - IgG glycosylation in autoimmune-prone strains of mice.
AB  - The relationship between increased levels of IgG oligosaccharide chains lacking
      galactose (G0) and the development of rheumatoid arthritis is unclear. In order
      to further our understanding of the observed correlation between raised serum G0
      and arthritis, we have studied G0 levels in arthritis-prone and non-susceptible
      (i.e. non-arthritis-prone) mice and the effects on G0 of mycobacterial antigens,
      which have been postulated to play a role in the early events leading to the
      development of arthritis. We have shown that different age-matched mouse strains
      have characteristic 'resting' levels of G0 which (in six out of seven strains of
      mice) increase with age. We have also shown that these increases can be enhanced
      by immunization of arthritis-prone strains of mice with an adjuvant containing
      mycobacteria (Freund's complete adjuvant (FCA)), suggesting that deflects in the
      ability to regulate these G0 changes may be related to susceptibility to
      arthritis.

PMID- 8287594
TI  - Immune complex-degradation ability of macrophages in MRL/Mp-lpr/lpr lupus mice
      and its regulation by cytokines.
AB  - Impaired clearance of circulating and/or deposited immune complexes (IC) by the
      mononuclear phagocytic system is one of the major factors in the pathogenesis of
      IC diseases. MRL/Mp-lpr/lpr (MRL/lpr) lupus mice spontaneously develop a lethal
      glomerulonephritis associated with IC deposition. The ability of macrophages to
      degrade phagocytozed IC and regulation of this degradation in MRL/lpr mice were
      examined. In 4-month-old MRL/lpr mice, macrophages accumulated in the affected
      glomeruli and these macrophages contained many phagosomes containing electron
      dense bodies. When culture supernatant of human T cell line HUT102 was
      administered intraperitoneally into disease-bearing MRL/lpr mice, degradation of
      these electron-dense bodies in the macrophages in glomeruli was noted. We
      developed a quantitative in vitro assay for IC degradation activity of MRL/lpr
      resident peritoneal macrophages (RPM) using peroxidase-labelled IC derived from
      MRL/lpr mouse sera. The ability of the RPM to degrade IC was remarkably enhanced
      by the pretreatment with HUT102 cell products and the related human recombinant
      cytokines, lymphotoxin and IL-1 alpha. Moreover, pretreatment of RPM from non
      diseased MRL/Mp-+/+ mice with the culture supernatant of spleen cells from
      diseased MRL/lpr mice reduced their IC degradation activity. These results
      suggested that the ability of macrophages to degrade IC in MRL/Mp strains of mice
      is under the regulation of cytokines, and the impaired ability in the disease
      bearing mice may be the result of abnormalities in the cytokine system in these
      mice.

PMID- 8287595
TI  - In vivo treatment with a monoclonal antibody to T helper cells in experimental
      autoimmune glomerulonephritis in the BN rat.
AB  - Experimental autoimmune glomerulonephritis (EAG) was induced in brown Norway (BN)
      rats by a single i.m. injection of homologous glomerular basement membrane (GBM)
      in Freund's complete adjuvant. This model of anti-GBM disease is characterized by
      the development, over several weeks, of circulating and deposited anti-GBM
      antibodies, accompanied by albuminuria. We examined the effects of treatment with
      MoAb W3/25 (anti-CD4) at different doses, starting at the time of immunization
      and continued for the duration of the study or for a limited period only.
      Continued treatment with W3/25, at a dose of 5 or 10 mg/kg intraperitoneally
      three times per week for 4 weeks, produced a marked reduction in circulating anti
      GBM antibodies, absence of detectable deposited antibody and virtual absence of
      albuminuria. When W3/25 treatment, at 5 or 10 mg/kg, was stopped after 2 weeks,
      there was still a significant reduction in anti-GBM antibodies and albuminuria at
      4 weeks. A similar effect on the disease was achieved when W3/25 was administered
      only three times during the first week at a dose of 30 mg/kg. Animals injected
      with W3/25 at a dose of 10 mg/kg through the course of disease showed < 10%
      W3/25+ cells by FACS analysis of splenic lymphocytes at week 4, while controls
      and animals treated for shorter periods showed > 30% W3/25+ cells. These results
      demonstrate that W3/25 can prevent the development of EAG, and that this effect
      is not dependent on persistent depletion of T cells. Further work is necessary to
      determine whether anti-T cell therapy is effective in established EAG, and may be
      worth investigating in human anti-GBM disease.

PMID- 8287596
TI  - The effect of anti-CD4 on helper function of CD4,45RA+ versus CD4,45RO+ T cells.
AB  - Here we have investigated and compared the effects of anti-CD4 on helper function
      of CD4,45RA+ versus CD4,45RO+ T cells. Only CD4,45RO+ cells, but not CD4,45RA+
      cells were able to promote B cell differentiation resulting in immunoglobulin
      production in vitro (IgM as well as IgG) which could be inhibited by anti-CD4
      MoAbs (MAX.16H5 and T151). In pokeweed mitogen (PWM)-induced B cell proliferation
      a similar pattern of responsiveness was obtained. When we studied the anti-CD4
      effects on cytokine production in T cells stimulated in mixed lymphocyte reaction
      (MLR) or by mitogens, we found that neither IL-2 nor IL-4 production was
      dramatically influenced by anti-CD4 in CD4,45RO+ cells. This led us to the
      conclusion that the inhibitory effect of anti-CD4 on B cell proliferation and
      immunoglobulin secretion was not due to inhibition of cytokine production. To
      clarify this point, we investigated the ability of anti-CD4 to inhibit conjugate
      formation between B and T cells. It was found that CD4,45RO+ T cells formed more
      conjugates than CD4,45RA+ cells, and that only the conjugate formation by
      CD4,45RO+ T cells was inhibited by anti-CD4. These results suggest that (i) anti
      CD4 inhibits T helper functions primarily by affecting CD4,45RO+ cells, and (ii)
      this effect is probably mediated by contact inhibition in the early phase of T-B
      collaboration.

PMID- 8287597
TI  - Bone marrow transplantation therapy using resistant donors for retrovirus-induced
      leukaemia in mice.
AB  - Infection with Rauscher leukaemia virus (RLV) causes erythroleukaemia, anaemia,
      viraemia, and splenomegaly, features which develop very quickly in mice of
      strains susceptible to RLV but more slowly or not at all in strains resistant to
      RLV. We compared the effects of bone marrow transplantation (BMT) of donor cells
      obtained from a mouse strain resistant to the virus with the effects of BMT of
      donor cells obtained from strains susceptible to the virus, in recipient virus
      susceptible mice which had previously been inoculated with RLV. Our results
      indicated that bone marrow transplantation from a marrow-resistant donor, but not
      from a susceptible donor, delayed the expression of leukaemia and delayed death,
      although such treatment did not appear to inhibit viral infection in susceptible
      recipients.

PMID- 8287598
TI  - Expansion of CD3+CD4-CD8- T cell population expressing high levels of IL-5 in
      Omenn's syndrome.
AB  - Omenn's syndrome is a fatal, autosomal-recessive combined immune deficiency
      characterized by several erythematous exfoliative eruptions, lymphadenopathy,
      hepatosplenomegaly, and elevated eosinophil count. In some of these patients an
      expansion of CD3+CD4-CD8- double negative (DN) T cell population was observed. We
      show here that the DN population represents a clonal expansion of T cells which
      preferentially use V beta 14 in their T cell receptor complex. Using polymerase
      chain reaction, we show that patient's DN cells express spontaneously high levels
      of IL-5, thus possibly explaining the abundance of eosinophils in this disorder.
      The increase of IgE observed in patients with Omenn's syndrome is unlikely to be
      related to IL-4 production, as IL-4 levels in patient samples were low. However,
      patient's low expression of interferon-gamma (IFN-gamma), which has been reported
      to inhibit IgE production, may explain the elevated levels of IgE in this
      patient. The results thus highlight the importance of the inhibitory effect of
      IFN-gamma on regulation of IgE production.

PMID- 8287599
TI  - T cell receptor gene rearrangements and cytotoxic activities of clones isolated
      from tumour-infiltrating lymphocytes (TIL) from melanoma patients.
AB  - The lymphocytes which infiltrate tumours and are grown in vitro to be used in
      adoptive immunotherapy are often characterized by dominant rearrangement of their
      T cell receptor (TCR) genes. To investigate the frequency and function of cells
      contributing to the 'dominant' rearrangement, we have cloned two bulk cell lines
      of TIL derived from melanoma patients (TIL-1 and TIL-5). These IL-2-propagated
      TIL cell lines had a CD8+ phenotype and exerted strong cytotoxic activity against
      autologous melanoma cells, but not against the natural killer (NK)-sensitive K
      562 cell line or LAK targets such as Daudi cells. We derived 40 clones from TIL-1
      and 23 from TIL-5. All tested clones were CD3+, CD4-, CD8+ and expressed the
      alpha/beta TCR. From TIL-1, 27 of 40 clones, and 13/19 of the TIL-5 clones lysed
      autologous tumour cells. In contrast to the NK-negative bulk cultures, K-562
      killing was detected in 21 of the TIL-1 clones and 17 of the TIL-5 clones. TIL-1
      contained eight clones and TIL-5 two clones with lytic capacity against neither
      autologous tumour cells nor the K562 cell line, although these clones possessed
      lytic potential as evidenced in a lectin-mediated lysis assay. LAK activity was
      not detected in most clones. Cytotoxic activity against autologous tumour could
      be inhibited by preincubation with anti-CD3 or anti-HLA class I MoAbs. Of the 34
      TIL-1 clones analysed, 15 shared a rearranged TCR beta EcoRI restriction fragment
      of approximately 9.5 kb with the bulk culture. Clones sharing the EcoRI 10.5-kb
      dominant band present in TIL-5 bulk culture were also isolated. When the pattern
      of TCR beta rearrangement was compared with the cytotoxic functions, the
      following conclusions could be drawn: (i) clones contributing to the dominant
      band had heterogeneous functions. Most killed autologous tumour cells, but clones
      with no cytotoxic activity or even with no proliferative capacity in response to
      autologous tumour cells were also detected among those contributing
      rearrangement; (ii) some clones that share an apparently identical rearranged
      band different from the 'dominant' rearrangement, may demonstrate the same
      cytotoxic function. In addition, our data suggest that many of the clones that
      share the dominant rearrangement originated from diverse progenitors. The high
      frequency of clonally diverse anti-tumour reactive TIL is likely to be a
      reflection of the in vivo selection of the TCR repertoire at the site of
      tumour.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8287600
TI  - Expression of high-affinity IL-4 receptors on human melanoma, ovarian and breast
      carcinoma cells.
AB  - It has previously been shown that murine sarcoma cells express high-affinity IL-4
      receptors (IL-4R) which are internalized after binding to the ligand (Puri et
      al., Cancer Res 1991; 51:3011-7). We have also reported that human renal cell
      carcinoma cells express high-affinity IL-4R, and IL-4 inhibits tumour growth in
      vitro (Obiri et al., J Clin Invest 1993; 91:88). In this study we investigated
      the expression and function of IL-4R on other human solid tumours. Human
      melanoma, ovarian carcinoma and breast carcinoma cell lines were assessed for the
      cell surface expression of IL-4R by radio-ligand receptor binding and for IL-4R
      gene expression by Northern blot analysis. Primary cultures of mesothelioma and
      neurofibrosarcoma cells were similarly investigated. Human melanoma, ovarian
      carcinoma and breast carcinoma cell lines expressed IL-4R on their cell surface
      with a dissociation constant (Kd) of 140-549 pM. These tumour lines expressed a
      single 4 kb species of mRNA for IL-4R. Similarly, primary cultures of
      mesothelioma and neurofibrosarcoma cells were positive for the IL-4R mRNA by
      Northern blot analysis. Fresh, non-cultured mesothelioma and neurofibrosarcoma
      tumour sections were also positive for the presence of IL-4R as determined by
      immunohistochemistry of frozen sections using anti-IL-4R antibody. In order to
      study possible functions of IL-4R, we evaluated the effects of IL-4 on cell
      growth and its effect on MHC antigen expression in the presence or absence of
      interferon-gamma (IFN-gamma). In tissue culture, IL-4 reduced the growth of
      tumour cell lines and primary cell cultures studied. IL-4 had very little effect
      on MHC class I antigen expression on ovarian, breast and melanoma cell lines;
      however, MHC class II (HLA-DR) expression was enhanced on melanoma and breast
      carcinoma cells. IL-4 also enhanced the IFN-gamma-induced class II expression on
      melanoma and breast carcinoma cells. Taken together, our observations indicate
      that IL-4R are expressed on a variety of human solid tumours and these receptors
      may be functional. IL-4 alone and in combination with IFN-gamma may play a role
      in host immune response against cancers.

PMID- 8287601
TI  - Avidity of Aspergillus umbrosus IgG antibodies in farmer's lung disease.
AB  - Farmer's lung disease (FL), the commonest form of allergic alveolitis caused by
      repeated inhalation of mouldy hay, is associated with exposure to the fungus
      Aspergillus umbrosus among Finnish farmers. The antigen-binding avidity of A.
      umbrosus-specific IgG antibodies was measured in 12 FL patients in acute phases
      of initial and recurrent attacks and during 1 year follow up as well as in 12
      healthy farmers and five healthy urban controls. The farmers' groups were further
      divided into two subgroups: subjects with short exposure (< 7 years) and subjects
      with long exposure (> 25 years). During the first acute phase FL patients with
      long exposure exhibited a high avidity of A. umbrosus-specific IgG antibodies
      that remained high during the 1 year follow up, although the A. umbrosus-specific
      IgG antibody titre decreased. A re-exposure to mouldy hay leading to a recurrence
      further enhanced the maturation of the antibody avidity, so that an even higher
      A. umbrosus-specific IgG avidity with a less significant increase of antibody
      titre occurred than during the first acute attack. Notably higher IgG antibody
      avidity was observed in FL patients with long exposure than in healthy farmers or
      in healthy controls.

PMID- 8287602
TI  - Regulation of C3 and factor H synthesis of human glomerular mesangial cells by IL
      1 and interferon-gamma.
AB  - Previous reports have shown production of complement components C4, C2 and factor
      B by renal tissue. We have shown recently that human proximal tubular epithelial
      cells (PTEC) synthesize C3 in vitro, and that IL-2 enhances this production. In
      the present study we demonstrate that human mesangial cells (MC) in culture
      produce factor H and that supernatants of activated peripheral blood mononuclear
      cells (T cell growth factor (TCGF)) induce C3 production and enhance factor H
      synthesis in both a time- and dose-dependent manner. To investigate whether
      certain defined cytokines from TCGF were responsible for the observed effect, we
      tested various cytokines for their effect on complement production by MC. It is
      shown that IL-1 induces C3 synthesis whereas factor H production is up-regulated
      by IFN-gamma, in both a dose- and time-dependent manner. Antibody blocking
      experiments revealed that C3 synthesis induced by both TCGF and IL-1 could be
      blocked with antibodies specific for IL-1, and also that TCGF and IFN-gamma
      enhanced factor H synthesis could both be blocked with antibodies specific for
      IFN-gamma. Cycloheximide was able to inhibit C3 and factor H production,
      suggesting de novo synthesis of the proteins. mRNA-polymerase chain reaction
      (PCR) analysis revealed mRNA encoding for C3 after stimulation with TCGF and IL
      1. Factor H genes are constitutively expressed in cultured mesangial cells and
      its expression is up-regulated by TCGF and IFN-gamma. Northern blot analysis with
      specific probes for C3 and factor H revealed bands which support the results
      obtained by PCR analysis.

PMID- 8287603
TI  - Erythrocytes from young but not elderly donors can bind and degrade immune
      complex- and antibody-bound C3 in vitro.
AB  - In situ aged erythrocytes (senescent erythrocytes from young donors and both
      young and old erythrocytes from elderly donors) demonstrate high levels of
      membrane-bound C3c and C3d and elevated susceptibility to in vitro phagocytosis.
      In this study we demonstrate that in situ aged erythrocytes are defective in
      their ability to degrade C3 fragments and clear them from the erythrocyte
      membrane. Erythrocytes from young donors bind complement-bearing immune complexes
      via CR1 and become susceptible to complement-mediated erythrophagocytosis
      ('innocent bystander' sequestration). Erythrocytes from elderly donors are
      defective in their ability to bind such immune complexes, as attested by the lack
      of an increment in membrane-associated C3 fragments as detected by flow cytometry
      and lack of an increment in in vitro sequestration. Factor I (serum)-dependent
      cleavage of C3 fragments and release of immune complexes from the erythrocytes of
      young donors lead to a drop in erythrocyte-associated C3 fragments and the
      disappearance of the 'innocent bystander' phenomenon. Inhibition of Factor I, and
      thus inhibition of C3b degradation and immune complex release for the erythrocyte
      membrane, enhances the levels of 'innocent bystander' sequestration of
      erythrocytes from young donors. Erythrocytes from elderly donors are defective in
      the dynamic process of CR1 binding of complement-bearing immune complexes and
      Factor I-associated release of membrane-associated C3 fragments. A defect in the
      ability of all in situ aged erythrocytes to clear their membranes of C3 fragments
      is also demonstrated for complement bound to the erythrocyte via IgM
      isoagglutinins. While erythrocytes from both young and elderly donors allow for
      the IgM-mediated binding of complement to the erythrocyte, only young
      erythrocytes from young donors demonstrate degradative activity with the release
      of membrane-associated C3c. Erythrocytes from elderly donors demonstrate lower
      levels of detectable CR1 (CD35), decay accelerating factor (DAF) (CD55) and
      Protectin (CD59) than do erythrocytes from young donors. Time course studies
      determine that the defect in handling of immune complexes observed for in situ
      aged erythrocytes is not due to differences in the kinetics of loading or
      releasing of immune complexes. These findings on the refractiveness of
      erythrocytes of elderly donors to uptake of immune complexes and the degradation
      of C3 fragments may be of importance not only in the understanding of erythrocyte
      sequestration, but also in the physiology of immune clearance in the elderly.

PMID- 8287604
TI  - Hereditary angioneurotic oedema: characterization of plasma kinin and vascular
      permeability-enhancing activities.
AB  - The mediator(s) responsible for localized enhanced vascular permeability that
      characterizes an exacerbation of hereditary angioneurotic oedema (HAE) is thought
      to be a product of either contact or complement system activation. In contrast to
      normal individuals, plasma from these patients generates both kinin and vascular
      permeability-enhancing activity following incubation at 37 degrees C. Depletion
      of C1 inhibitor in both normal and C2-deficient plasma, but not in contact factor
      deficient plasmas, resulted in generation of these activities. The kinin activity
      from incubated HAE plasma was susceptible to kininase inactivation and was
      blocked by a Bk2 receptor antagonist. Furthermore, this activity was isolated
      from HAE plasma; amino acid sequence analysis proved it to be bradykinin.
      Similarly, the vasopermeability-enhancing activity from ethanol-fractionated or
      boiled HAE plasma, collected during either attack or remission, co-eluted with
      bradykinin on reverse-phase high performance liquid chromatography (HPLC). These
      studies conclusively demonstrate that bradykinin is the major kinin and mediator
      of enhanced vascular permeability generated during incubation of HAE plasma. The
      role of other bioactive products, such as the C2 kinin, at local sites of oedema
      formation remains to be further defined.

PMID- 8287605
TI  - Intraglomerular expressions of IL-1 alpha and platelet-derived growth factor
      (PDGF-B) mRNA in experimental immune complex-mediated glomerulonephritis.
AB  - Both PDGF and IL-1 play important roles as autocrine growth factors for cultured
      mesangial cells, and may be closely associated with the progression of
      glomerulonephritis. In this study we investigated intraglomerular expressions of
      PDGF-B and IL-1 alpha mRNA in mice with bovine serum albumin (BSA) nephritis, a
      model of immune complex-mediated glomerulonephritis, using the reverse
      transcription-polymerase chain reaction (RT-PCR) method. We also quantified
      intraglomerular PDGF-B mRNA by the competitive PCR and studied the correlation
      between the level of intraglomerular PDGF-B mRNA expression and the degree of
      observed glomerular injury. While expression of neither PDGF-B nor IL-1 alpha
      mRNA was detected in glomeruli from control mice, both were strongly expressed in
      glomeruli from mice with BSA nephritis. IL-1 alpha mRNA in glomeruli showed low
      accumulation in mice with mild glomerular injury, and was increased in mice with
      moderate glomerular injury. In contrast, high intraglomerular expression of PDGF
      B mRNA occurred in all mice with mild glomerular injury and continued throughout
      the course of the disease. We observed no correlation between the level of PDGF-B
      mRNA expression and the histologic grade of renal damage. These results suggest
      that PDGF and IL-1 have different growth properties, and PDGF might play a role
      as a competence factor rather than a progression factor in the pathogenesis of
      immune complex-mediated glomerulonephritis.

PMID- 8287606
TI  - In vivo expression of human immunoglobulin germ-line mRNA in normal and in
      immunodeficient individuals.
AB  - Previous in vitro studies suggest that transcription of the unrearranged
      immunoglobulin switch region and its 5' flanking region precedes isotype
      switching. These transcripts, which are devoid of a variable region, contain
      unique exons and are called germ-line (GL) mRNA. A crucial point in this regard
      is whether such transcripts could be detected in vivo, and if their expression
      correlates with immunoglobulin class switching in health and disease. To
      understand the in vivo role of this transcriptional activity we have adapted the
      reverse transcription-polymerase chain reaction (PCR) to analyse the GL
      transcripts from unstimulated peripheral blood mononuclear cells (PBMC) in
      healthy individuals and in different immunological diseases. Furthermore,
      mononuclear cells from different human organs were also analysed. We report here
      that GL (I alpha, I gamma and I epsilon used to designate the GL mRNA for IgA,
      IgG and IgE, respectively) mRNA are expressed differentially during ontogeny of B
      cells. Unexpectedly, no difference of I alpha mRNA expression between the PBMC
      and the secondary lymphoid organs was detected. Rather, the levels of GL
      transcripts were correlated to the number of sIgM+ cells. GL mRNA of all three
      isotypes could be detected in PBMC from healthy donors, whereas there was a
      decrease of specific GL transcript synthesis in individuals with immunoglobulin
      deficiency. Furthermore, during the in vivo immune response in a parasitic
      infection, we could demonstrate an induction of GL I epsilon mRNA during in vivo
      immune response. Concomitantly, there was also increased synthesis of productive
      epsilon transcripts. These findings implicate a potential role of GL
      transcription during in vivo immunoglobulin class switching.

PMID- 8287607
TI  - Low antibody affinity restricted to the IgA isotype in IgA nephropathy.
AB  - Antibody affinity affects the handling and behaviour of immune complexes, and
      experimental studies have shown that animals which produce predominantly low
      affinity antibody are prone to immune complex deposition resulting in
      glomerulonephritis. In order to investigate the potential role of antibody
      affinity in the pathogenesis of IgA nephropathy, affinity of both IgA and IgG
      antibody isotypes during secondary response to systemic immunization with tetanus
      toxoid was studied in 20 patients with IgA nephropathy. Patients with IgA
      nephropathy produced IgA antibodies of significantly lower affinity than controls
      (P < 0.001), whereas IgG antibody affinities were similar. Contrasting with
      controls, patients' IgA antibody affinity was inversely related to antibody
      concentration, with higher responders producing large amounts of low-affinity
      antibody. IgG antibody affinity increased with time, and maturation of IgG
      antibody affinity was similar in both controls and patients. IgA affinity in
      controls decreased with time, and this lack of IgA affinity maturation may
      explain the relative unimportance of IgA in normal systemic immunity. This
      temporal decrease in IgA affinity was not observed in patients with IgA
      nephropathy. The production of low-affinity IgA in IgA nephropathy may provide an
      explanation for the predominant deposition of IgA in this disease.

PMID- 8287608
TI  - Antineutrophil cytoplasm antibodies (ANCA) of IgA isotype in adult Henoch
      Schonlein purpura.
AB  - ANCA are associated with certain forms of systemic vasculitis, and have been
      reported previously to be of the IgG and IgM isotype. We examined the possible
      association between IgA ANCA and the IgA-related diseases Henoch-Schonlein
      purpura (HSP) and IgA nephropathy (IgAN). IgA and IgG ANCA were detected by
      isotype-specific solid-phase assays with a crude neutrophil extract, and their
      presence was confirmed by antigen-specific fluid-phase competitive inhibition
      tests and by indirect immunofluorescence. The possible interference by IgA
      rheumatoid factor was excluded. IgA ANCA were detected in sera from 11/14 HSP
      patients (79%), from 1/30 IgAN patients (3%), from 1/40 patients with
      vasculitides classically associated with IgG ANCA (2.5%), and in none of 60 sera
      from healthy blood donors. IgG ANCA were present with IgA ANCA in three patients
      with HSP. Only one HSP serum had anti-myeloperoxidase (MPO) activity by both IgA
      and IgG isotype-specific ELISA, and none was positive for proteinase 3 (PR3).
      Western blot analysis performed with neutrophil extract showed that the four
      strongest IgA ANCA-positive HSP sera reacted with a 51-kD protein; Western blot
      performed on cellular fractions showed that this protein is primarily membrane
      associated, and different from fibronectin. Our study suggests that adult HSP is
      closely associated with circulating IgA ANCA, which may be directed against a
      different autoantigen than that recognized by IgG ANCA.

PMID- 8287609
TI  - Uveitis and anti-neutrophil cytoplasmic antibodies.
AB  - Serum samples of 485 uveitis patients were screened for the presence of anti
      neutrophil cytoplasmic antibodies using a standardized immunofluorescence test
      (IIF) on neutrophil granulocytes. Seventeen of these sera contained cytoplasmic
      (C)-ANCA antibodies, while two of the sera contained perinuclear (P)-ANCA
      antibodies (both antinuclear antibody (ANA)-positive, one anti-myeloperoxidase
      (MPO)-positive). None of the C-ANCA-positive sera reacted with proteinase-3 in
      ELISA using a highly purified proteinase-3 preparation. Four C-ANCA and one P
      ANCA-positive serum reacted with MPO. The majority of the sera did react with
      azurophilic granules in ELISA. The implication of these results is that in
      patients with uveitis a positive C-ANCA test is not diagnostic for Wegener's
      granulomatosis, but is most probably caused by the presence of autoantibodies
      against as yet unknown constituents of azurophilic granules.

PMID- 8287610
TI  - Production and secretion of interferon-gamma (IFN-gamma) in children with atopic
      dermatitis.
AB  - IFN-gamma is known to be a major inhibitor of IgE synthesis in vitro. Recent
      studies demonstrating reduced production of IFN-gamma in children and adults with
      atopic dermatitis and elevated serum IgE suggest a similar role for this cytokine
      in vivo. The reasons for this reduced IFN-gamma production are not known. One
      possibility is that atopic individuals have a reduced population of cells
      producing IFN-gamma in vivo. Using a fluorescence-labelled antibody to detect
      intracellular IFN-gamma, the percentage of IFN-gamma-producing cells was
      determined in children with atopic dermatitis and in non-atopic controls.
      Children with atopic dermatitis had a greater percentage of IFN-gamma-producing
      cells in unstimulated cultures compared with controls, indicating in vivo
      activation of lymphocytes in the atopic group. This could reflect the significant
      degree of inflammation present in these children, or the presence of bacterial
      infection or colonization. Although secretion of IFN-gamma after stimulation with
      phorbol myristate acetate (PMA)/Ca was significantly lower in children with
      atopic dermatitis compared with controls, the percentage of IFN-gamma-producing
      cells in the stimulated cultures from this group was equivalent to controls. This
      demonstrates that the reduced ability of atopic children to secrete IFN-gamma in
      vitro does not relate to a lack of IFN-gamma-producing cells, but to a difference
      in the regulation of IFN-gamma production beyond the stage of signal
      transduction.

PMID- 8287611
TI  - Long-term ultraviolet B-induced impairment of Langerhans cell function: an
      immunoelectron microscopic study.
AB  - The influence of low-dose, long-term ultraviolet B (UVB) light exposure on HLA
      class II-positive human epidermal Langerhans cells (LC) was studied using a
      sensitive immunoelectron microscopic technique for the ultrastructural assessment
      of HLA class II expression on LC and for quantification of these cells in situ.
      Six healthy Caucasian volunteers participated in the experiments and received
      thrice weekly UVB treatments for 4 weeks. The initial dose ranged from 30 to 50
      mJ/cm2 and the total dose from 600 to 3500 mJ/cm2, depending on skin type.
      Suction blisters and biopsies were obtained before the start of the UVB protocol
      and 48 h after the last UVB irradiation, and processed for the mixed epidermal
      cell-lymphocyte reaction (MECLR) and electronmicroscopy, respectively. The MECLR
      was used as a measure of the immune response. The distribution of HLA class II
      molecules on LC was studied by incubating ultrathin cryosections of human skin
      tissue with an anti-HLA class II MoAb that was conjugated to 10 nm colloidal
      gold. Furthermore, the number of LC was assessed ultrastructurally, when they
      could be recognized by their unique cytoplasmic organelle, the Birbeck granule
      (BG). The UVB protocol that was employed caused a marked suppression of the MECLR
      responses. This UVB-induced reduction of the immune response was not paralleled
      by changes in HLA class II expression on LC, nor in the number of epidermal LC.
      These findings are further support for our hypothesis that UVB-induced immune
      suppression in the skin is not due to a depletion of local LC.

PMID- 8287612
TI  - Immunological diagnosis of childhood coeliac disease: comparison between
      antigliadin, antireticulin and antiendomysial antibodies.
AB  - The immunological markers proposed to supplement intestinal biopsy for the
      diagnosis of coeliac disease are antigliadin, antireticulin and antiendomysial
      antibodies. These antibodies have been studied separately or compared as pairs,
      but no prospective comparison of all three antibodies in childhood coeliac
      disease exists. Thirty-four confirmed coeliacs were compared with nine non
      coeliacs with pathological small intestines, and 32 children with a normal
      intestinal histology. Sera were examined for IgG- and IgA-antigliadin antibodies
      (AGA) by ELISA, and for IgA-antireticulin antibodies (ARA) and IgA endomysial
      antibodies (EMA) by indirect immunofluorescence. In active coeliac disease, IgA
      EMA was the most sensitive (97%), while IgA-AGA the least sensitive antibody
      (52%). The specificity of IgA-AGA, IgG-AGA, IgA-ARA, IgA-EMA was 95%, 92%, 100%
      and 98%, respectively. Positive predicted values of ARA and EMA were comparable
      (97-100%), while EMA had the highest negative predicted value (98%). Compared
      with IgG-AGA, IgA-EMA titres better reflected variations in dietary gluten, and
      correlated best with intestinal pathology. Compared with AGA and ARA sensitivity,
      specificity and predictive values, EMA is the most reliable serological marker
      for the diagnosis of coeliac disease. It reflects dietary changes in gluten and
      correlates best with intestinal histopathology. Therefore, it should be
      considered the best of the three serological tests available for childhood
      coeliac disease.

PMID- 8287613
TI  - Human TcR gamma delta+ lymphocyte response on primary exposure to Plasmodium
      falciparum.
AB  - In 29 patients experiencing their first P. falciparum malarial attack, blood
      levels of TcR gamma delta+ lymphocytes were studied from the onset of infection
      to up to 6-9 months later. Blood TcR gamma delta+ lymphocytes, revealed using the
      TcR delta 1 monoclonal antibody (MoAb), were increased both in absolute and
      relative numbers. Alterations lasted for up to 3-4 months following the attack. A
      Ti gamma A/BB3 reactive V gamma 9 subset was preferentially amplified. In vitro,
      TcR gamma delta+ lymphocytes from both malaria-sensitized and unprimed donors
      responded to P. falciparum schizont extract (PFSE). PFSE-stimulated polyclonal T
      cell lines consisted principally in TcR gamma delta+ cells with a Ti gamma
      A+/BB3+ phenotype. Several TcR gamma delta+ T cell clones obtained from patients
      recovering from acute malarial attack were maintained in the presence of PFSE and
      autologous irradiated PBL. They belong to the V gamma 9 subset. In long-term
      cultures, TcR gamma delta+ clones progressively lost their capacity to react to
      PFSE antigen while they were able to proliferate and to exert cytotoxic activity
      in response to autologous TcR alpha beta+, PFSE-specific T lymphocyte clones.
      This suggests that regulatory interactions occur between activated TcR gamma
      delta+ and TcR alpha beta+ cells generated by P. falciparum. Sequential
      variations in blood TcR gamma delta+ and TcR alpha beta+ lymphocyte levels after
      primary exposure to P. falciparum suggest that such regulatory interactions may
      occur in vivo.

PMID- 8287614
TI  - Human intestinal alkaline phosphatase-binding IgG in patients with severe
      bacterial infections.
AB  - Patterns of alkaline phosphatase (AP)-binding proteins were observed in the
      alkaline pH range of 6.5-9.5 upon isoelectric focusing and blotting of serum from
      patients with inflammatory diseases. After isolation using affinity
      chromatography on protein A or immunoaffinity chromatography on AP coupled to
      cyanogen bromide (CNBr)-activated Sepharose, the AP-binding protein was
      identified as IgG on Western blots and in ELISA using human IgG-specific
      antibodies. It was shown that this IgG binds to AP from both calf (bovine) and
      human intestine. However, it binds neither to the human liver-bone-kidney (LBK)
      isoform nor to bacterial AP. Moderate reaction was observed with human placental
      AP. Comparing patients with various diagnoses (n = 284), AP-binding antibodies
      were mainly found in severe bacterial infections. They were not detected in serum
      from healthy blood donors (n = 300). The presence of AP-binding IgG was
      independent of the infected organ and the bacterial species causing infection.
      This antibody may be useful for discriminating bacterial from viral infection and
      for indicating severe bacterial inflammation.

PMID- 8287615
TI  - Comparison of techniques for measurement of gelatinases/type IV collagenases:
      enzyme-linked immunoassays versus substrate degradation assays.
AB  - Radiolabeled substrate degradation assays and gelatin zymography are routinely
      employed to assay 72 kDa gelatinase A (MMP-2) and 92 kDa gelatinase B (MMP-9) in
      biological fluids. Enzyme-linked immunosorbent assays (ELISA) have recently been
      developed for the quantitation of these matrix metalloproteinases (MMP). In this
      study, we have compared ELISA to standard substrate degradation assays for
      measurement of MMP-2 and MMP-9 in human plasma and tumor-conditioned media.
      Gelatin Sepharose chromatography and gel filtration chromatography were employed
      as partial purification procedures for MMP-2 and MMP-9. The ELISA data for MMP-2
      and MMP-9 are linear on a log:log regression curve over a wide range of MMP
      concentrations and are specific for the designated gelatinase, with no overlap
      detected with related metalloproteinases. The minimum detectable concentrations
      of MMP-2 and MMP-9 were approximately 0.5 ng/ml and 0.2 ng/ml, respectively, in
      the ELISA as compared to 4 ng/ml and 3 ng/ml, respectively, in gelatin
      zymography. The [3H]gelatin degradation assay required a combination of > 50
      ng/ml of MMP-2 and MMP-9 for detection. Although gelatin zymography was less
      sensitive than ELISA (primarily due to the smaller sample volume employed) and
      was more difficult to quantitate, this procedure offers the important advantage
      of being able to distinguish between latent and activated gelatinases.

PMID- 8287616
TI  - The stable prostacyclin analogue Cicaprost inhibits metastasis to lungs and lymph
      nodes in the 13762NF MTLn3 rat mammary carcinoma.
AB  - Prostacyclin and its stable analogues have been shown to interfere specifically
      with certain steps of the metastatic cascade. The antimetastatic activity of the
      stable prostacyclin analogue Cicaprost (Schering AG) on haematogenous metastasis
      in a series of tumours in rats and mice has been well established. In order to
      test the effect of Cicaprost on lymphogenous metastasis we chose the metastatic
      cell clone MTLn3 derived from the 13762NF rat mammary carcinoma. The effect of
      Cicaprost on prevention of lung metastasis, lymph node metastasis and primary
      tumour growth was investigated. Cicaprost given in daily doses of 0.01, 0.03 and
      0.1 mg/kg orally, reduced the number of lung metastases in a dose-dependent
      manner. Whereas the median number of lung metastases in the controls was greater
      than 1000, Cicaprost at a dose of 0.1 mg/kg reduced the number of lung metastases
      to between 11 and 100. The weight of the ipsilateral axillary lymph nodes was
      diminished by Cicaprost to 30-50% of controls. Moreover, metastasis to the
      contralateral axillary lymph node was completely inhibited by Cicaprost at all
      three doses tested. Cicaprost did not influence the growth rate of the MTLn3 cell
      clone implanted into the mammary fat pad or the weight of the primary tumour at
      the end of treatment. In conclusion, in addition to its dose-dependent effect on
      haematogenous metastasis, Cicaprost strongly inhibits lymph node metastasis.

PMID- 8287617
TI  - Clonal dominance detected in metastases but not primary tumors of retrovirally
      marked human breast carcinoma injected into nude mice.
AB  - Human breast cancer cell lines which grow in athymic (nude) mice provide a model
      of tumor cell growth and metastasis. Marking transplanted tumor cell populations
      with retroviral vectors provides a means of studying the dynamics of tumor cell
      growth in vivo. We evaluated three human breast cancer cell lines, MDA-MB-435,
      MDA-MB-231 and MCF-7, and found the cells were highly susceptible to retroviral
      gene transfer after a single 2-h exposure (90.9%, 62.7% and 72.3%, respectively).
      MDA-MB-435 cells (5 x 10(5)) marked with a retroviral vector containing the beta
      galactosidase gene (approximately 10(4) uniquely marked clones) were injected
      into the mammary fat pad of athymic mice to study clonal dominance. Primary
      tumors resected 10 weeks after injection expressed beta-galactosidase,
      demonstrating persistent vector expression in vivo. Southern blot analysis did
      not reveal clonal dominance in the primary tumors of the five mice studied. In
      contrast, pulmonary metastases in each animal were monoclonal or biclonal. These
      results demonstrate clonal dominance in pulmonary metastases but not primary
      tumors of retrovirally marked MDA-MB-435 cells. Our findings suggest that this
      model may also be used to introduce retroviral vectors expressing oncogenes, and
      anti-sense oncogenes, to determine their effect on tumor cell proliferation and
      metastasis in vivo.

PMID- 8287618
TI  - In vivo activation of NK cells induces inhibition of lung colonization of H-2
      positive and H-2 negative fibrosarcoma tumor clones.
AB  - The role of different tilorone analogs in the abrogation of the metastatic spread
      of H-2 positive and H-2 negative tumor clones was studied. Pre-treatment of
      BALB/c mice with RMI 10,874DA compound completely abolished lung colonization of
      an H-2 negative (GR9.B9) MCA-induced fibrosarcoma clone in an experimental
      metastasis assay. This effect was also evident when clones were treated with
      other tilorone analogs (R11,567DA or R11,513DA). Other H-2 positive and H-2
      negative chemically induced fibrosarcoma clones were also tested. The effect was
      not due to direct toxicity of the tilorone analog on tumor cells, but instead was
      dependent on NK cells; this was suggested by the finding that treatment of mice
      with anti-asialo GM1 abrogated the effect of the tilorone analog (RMI 10,874DA
      compound). Interestingly, the inhibition of lung colonization after intravenous
      injection was again observed regardless of the H-2 phenotype of the tumor clones,
      and H-2+ and H-2- clones were similarly inhibited. In vitro assays of NK
      sensitivity of tumor clones showed that lysis varied depending on the H-2
      phenotype of tumor clones, indicating an absence of correlation between in vivo
      and in vitro results.

PMID- 8287619
TI  - Interleukin-2 therapy of lymphoma-bearing immunosuppressed mice.
AB  - In the present study, the immune status of syngeneic Balb/c animals bearing a
      poorly metastatic RAW117-P lymphoma and the highly malignant liver metastatic
      variant RAW117-H10 lymphoma were measured and compared to control animals with no
      known tumor. The immune status was evaluated by performing various analyses of
      spleen cells for the frequencies of immune cells using flow cytometry, in vitro
      mitogen response and in vitro NK cell-mediated cytotoxicity assays on days 6, 9
      and 12 after tumor transplantation. The results of these studies indicated that
      from day 9 onwards, some of the immune response of the RAW117 lymphoma-bearing
      animals appeared to decrease compared to control animals. In order to boost the
      immune response of the tumor-bearing immunosuppressed animals, recombinant
      interleukin-2 (rIL-2) was administered to RAW117-H10 lymphoma-bearing animals.
      The immune status of tumor-bearing animals treated with rIL-2 was evaluated on
      days 5, 10 and 15 after tumor transplantation using similar analyses of spleen
      cells as described above. The results of these experiments indicated that IL-2
      treatment increased splenic levels of cytotoxic cells, and decreased the in vivo
      tumorigenicity/metastasis of metastatic RAW117-H10 lymphoma cells. rIL-2
      administration resulted in a significant increase in survival of tumor-bearing
      animals, and histological studies showed significantly lower tumor burdens in
      treated animals: it appears that rIL-2 has a beneficial therapeutic effect on
      immunosuppressive metastatic RAW117 lymphoma.

PMID- 8287620
TI  - Tumor cell surface beta 1-6 branched oligosaccharides and lung metastasis.
AB  - NIH3T3 cells transfected with an activated Ha-ras oncogene were treated with L
      PHA, the leukoagglutinin from red kidney beans. Cell lines resistant to L-PHA
      mediated cytotoxicity were isolated and found to contain reduced levels of L-PHA
      binding oligosaccharides. The levels of N-acetylglucosaminyltransferase V, the
      enzyme responsible for the initiation of the beta 1-6 branch, were reduced in L
      PHA-resistant cells. Tumorigenicity in nude mice was unchanged by the change in
      oligosaccharide expression, but the ability to form lung tumors after intravenous
      injection was significantly reduced. These results demonstrate that the ability
      of NIH3T3 cells transfected with an activated Ha-ras oncogene to form lung tumors
      after intravenous injection into nude mice is reduced in all six L-PHA selected
      cell lines containing a reduction in beta 1-6 branched Asn-linked
      oligosaccharides.

PMID- 8287621
TI  - Differences of E-cadherin expression levels and patterns in primary and
      metastatic human lung cancer.
AB  - Normal lung epithelium and 52 lung carcinomas obtained at surgical resection were
      examined by immunofluorescence for their expression levels and patterns of the
      calcium-dependent intercellular adhesion molecule E-cadherin. In dysplastic lung
      tissue and in well-differentiated squamous cell and adenocarcinomas, expression
      of E-cadherin was confined to the lateral cell border, similar to the expression
      level and pattern of normal lung tissue. The E-cadherin level was reduced and
      expression pattern was spotty or diffuse in moderately and poorly differentiated
      squamous cell and in small cell carcinomas of the lung. Most metastases resected
      also had a reduced level and an altered pattern of E-cadherin expression. In
      contrast, no such correlation was found in adenocarcinomas of the lung. This
      indicates that different cellular mechanisms are responsible in the progression
      of squamous cell carcinomas and adenocarcinomas of the lung.

PMID- 8287622
TI  - Retinoic acid negatively regulates beta 4 integrin expression and suppresses the
      malignant phenotype in a Lewis lung carcinoma cell line.
AB  - Retinoic acid (RA) is a potent inhibitor of the malignant phenotype and of tumour
      cell growth. We observed that in vitro RA treatment of a highly metastatic lung
      carcinoma cell line (C87) induced a marked reduction in the amount of the beta 4
      integrin subunit. The downregulation of this adhesion molecule was assessed by
      immunofluorescence, immunoprecipitation, and northern analysis. In order to
      investigate the effects of RA on the malignant phenotype in C87 cells we
      performed morphological and functional analysis after RA treatment. We found that
      RA was able to produce marked changes in C87 cell shape, increasing the number of
      flat cells (90% of the total cell population), and significantly inhibiting the
      malignant and invasive phenotype of C87 cells. RA treatment suppressed their
      clonogenic potential in soft agar (control, 20 +/- 5; RA, 0), and strongly
      reduced their chemotactic and chemoinvasive capacity (chemotaxis: control, 231 +/
      5; RA, 28 +/- 0; chemoinvasion: control, 132 +/- 11; RA = 2 +/- 1). FACS
      analysis and cell count, however, indicated that RA reduced the growth of C87
      cells only partially. After 72 h of treatment we observed only a 10% reduction in
      the S phase fraction of the cell population. Finally, the reduced lung colony
      forming ability, observed after i.v. injection of RA-treated cells (lung
      foci/animal: RA-treated cells, 1 +/- 0.1; untreated, 8.5 +/- 0.8), further
      supports the conclusion that in this murine lung carcinoma cell line a marked
      reduction in the expression of the beta 4 integrin subunit is associated with a
      marked inhibition of the malignant phenotype.

PMID- 8287623
TI  - Tumorigenicity of mouse T lymphoma cells is controlled by the level of major
      histocompatibility complex class I H-2Kk antigens.
AB  - We have previously found that an increased tumorigenicity and spontaneous
      metastatic potential of BW5147-derived T lymphoma cells was associated with a
      decrease in major histocompatibility complex (MHC) class I H-2Kk antigen
      expression. This suggested that H-2Kk antigens may control the tumorigenic
      potential of BW T lymphoma cells. Our current experiments aimed to prove this
      association by specifically altering H-2Kk expression by gene transfection.
      Transfected cells expressing a high level of H-2Kk antigens were significantly
      less tumorigenic and metastatic after subcutaneous inoculation. However, there
      was selection in vivo for cells expressing a reduced level of H-2Kk antigens,
      which concomitantly led to an increased tumorigenicity. These data further
      confirmed the strong association between H-2Kk expression and tumorigenicity. We
      subsequently tested whether the immune system is implicated in this phenomenon by
      inoculating the H-2Kk transfectants into irradiated, immunocompromised
      recipients. Our results indicate that the reduced tumorigenicity of the BW H-2Kk
      transfectants is due to an immune rejection mechanism, mediated by CD8+ immune
      effector cells, as revealed by in vivo depletion experiments with anti-CD8
      antibodies. Hence, we hereby demonstrated that H-2Kk antigens increased the
      immunogenicity of BW cells, via a CD8-dependent mechanism, which consequently
      reduced their tumorigenicity.

PMID- 8287624
TI  - Frequency and topographical distribution of CD68-positive macrophages and HIV-1
      core proteins in HIV-associated brain lesions.
AB  - We report the neuropathological and immunohistochemical findings in the brains of
      14 AIDS patients with HIV-related encephalopathy. Clinically, half of the
      patients presented with severe AIDS dementia complex including advanced
      psychomotor retardation and behavioural dysfunction. These features correlated
      with striking cerebral atrophy and subcortical lesions visible in CT and/or MRI
      scans. In 7 cases early signs of impaired memory and concentration and/or
      psychomotor slowing were apparent accompanied by subcortical lesions in MRI scans
      and normal CCTs. In order to investigate the topographical distribution of HIV-1
      associated features, in every case tissue samples from the frontal, temporal,
      parietal, occipital cortex and subcortical white matter, the hippocampus, basal
      ganglia, midbrain, pons, medulla oblongata and cerebellum were studied. In all
      patients histological examination disclosed the typical cellular constituents of
      HIV encephalitis (n = 12) or leukoencephalopathy (n = 2). Antibodies against
      lymphocyte subsets, CD68 antigen, myelin basic protein and GFAP were used to
      characterize the phenotype of cells and to highlight the white matter gliosis.
      The distribution and degree of pathological features were analysed in a
      semiquantitative scale, based on the number of CD68-positive cells, and disclosed
      great interindividual differences concerning the affected brain regions which
      only in part correlated with the severity of the clinical picture. It is
      noteworthy, that the deep gray matter, in particular putamen and thalamus, was
      involved in every case, independent from the stage of the disease. In addition,
      quantity and topographical distribution of HIV-1 core protein p24 were studied by
      use of two monoclonal antibodies. It is noteworthy, that the number of
      immunoreactive multinucleated giant cells and microglial cells decreased
      gradually from the deep gray matter, especially putamen and thalamus, and deep
      white matter to corpus callosum, cerebellar white matter and subcortical cerebral
      white matter. The topographical predilection of the deep gray matter even in
      cases with early cognitive decline indicates that the basal ganglia are affected
      early in the course of the disease. This observation closely resembles the
      results of highly sensitive quantitative neuropsychological tests which disclosed
      slowing and impaired coordination of rapid extremity movements indicating basal
      ganglia lesions even in early stages of HIV dementia.

PMID- 8287625
TI  - Silent solitary right parietal chondroma resulting in secondary mania.
AB  - We are reporting a case of manic depressive illness in a patient with a falxial
      chondroma in the right parietal region. Neurological symptoms were absent except
      for right hemicranial headache and examination was normal, prior to the
      presentation with mania. The mania responded to psychotropics. Subsequent
      evaluation with a head CT scan using contrast enhancement showed a 2.5 x 2 cm
      high density mass which on craniotomy and biopsy was noted to be a chondroma. For
      two years following removal, the patient remained euthymic without medication. To
      our knowledge, this is the fourth reported case of a chondroma in the parietal
      region and the first case of secondary mania associated with such a tumor.

PMID- 8287626
TI  - Atypical diffuse Lewy body disease with neuritic abnormalities.
AB  - Dementia associated with cortical and subcortical Lewy bodies (LB's) is a
      distinct entity with variable clinico-pathological presentation. We present the
      case of a 49-year-old male with progressive dementia. At autopsy, the brain
      showed diffuse cortical atrophy and ubiquitin-positive LB's in the dentate gyrus,
      deep layers of the neocortex, basal ganglia, nucleus basalis and substantia
      nigra. Thioflavine S stains of the neocortex and hippocampus were negative for
      the presence of plaques and tangles. Anti-ubiquitin immunostaining revealed
      abundant dystrophic neurites, torpedo-like axons and abnormal neuritic processes
      in the molecular layer of the dentate gyrus, pyramidal cell layer in CA1,
      subiculum, deep layers of the neocortex, claustrum, caudate, putamen and globus
      pallidus. Relatively mild neuritic alterations were observed in the nucleus
      basalis of Meynert (NbM) and locus ceruleus. The presence of this unique type of
      axonal damage associated with Lewy body disease, in the absence of plaques and
      tangles, might suggest a divergent mechanism of neuritic injury in the wide
      spectrum of this disorder.

PMID- 8287627
TI  - Immunohistochemistry of synapsin I and synaptophysin in human nervous system and
      neuroendocrine tumors. Applications in diagnostic neuro-oncology.
AB  - Synapsin I is a phosphoprotein localized to the cytoplasmic surface of synaptic
      vesicles and is one of the best characterized neuron-specific proteins.
      Synaptophysin is an integral membrane glycoprotein, also located on presynaptic
      vesicles, which has been shown to be a useful immunohistochemical marker for
      neuroendocrine/neuronal differentiation in tumor diagnosis. The sensitivity and
      specificity of immunohistochemical staining for these two proteins in formalin
      fixed, paraffin-embedded tissues was studied in a series of 67 neuroectodermal,
      neuroendocrine, and non-neural tumors. Intense immunoreactivity for both synapsin
      I and synaptophysin was observed in tumors containing well-differentiated neurons
      (gangliocytoma, ganglioglioma, neurocytoma). In these tumors, immunostaining was
      primarily concentrated along the outer surface of the cell membrane of the
      neuronal cells. Primitive neuroectodermal tumors (PNETs) (cerebral PNET,
      medulloblastoma, neuroblastoma) and most neuroendocrine tumors generally showed
      less intense and more variable immunoreactivity for these proteins. In most
      cases, immunostaining for synapsin I was sharper and often more intense than for
      synaptophysin. Some PNETs and neuroendocrine tumors that were immunoreactive for
      synapsin I did not stain for synaptophysin. We conclude that synapsin I is a
      reliable, sensitive immunohistochemical marker for neuronal/neuroendocrine
      differentiation in human neoplasms and may offer some advantages over
      synaptophysin when applied to formalin-fixed, paraffin-embedded tissues,
      particularly in the evaluation of primitive neuroectodermal tumors and
      neuroendocrine tumors.

PMID- 8287628
TI  - Chronic multifocal neuropathy with persistent conduction block (Lewis-Sumner
      syndrome). A clinico-morphologic study of two further cases with review of the
      literature.
AB  - We present data of 2 patients suffering from chronic motor-sensory multifocal
      neuropathy with persistent conduction block. The first case concerns a 9-year
      follow-up of a female, aged 24 years at onset with persistent multiple conduction
      blocks and a tendency towards generalization of clinical deficits. Eight years
      after onset sural nerve biopsy revealed extreme interfascicular variations of
      de/remyelination, onion bulb formation, fiber loss, edema, and proliferation of
      basal lamina of endoneurial capillaries. Serum antibodies against GM1
      gangliosides were not detected. The second case, a 29-year-old Yemenitic male
      with a 5-year history, exhibited conduction blocks in motor and sensory fibers,
      and a normal sural nerve biopsy. Our results are discussed with respect to those
      of some 30 cases individually reported in the literature.

PMID- 8287629
TI  - An electronic tutorial of neurosurgical pathology--application of multi-media in
      clinical pathology.
AB  - We present an electronic tutorial of neurosurgical pathology developed for
      standard MS-DOS-computers. No additional software requirements are necessary.
      Digital pictures are displayed on the computer screen in Super-VGA quality. The
      user interface allows a dialogue between the pathologist and the engine. The
      dialogue component consists of scroll bar menus with lists of possible
      suggestions and answers. For each case the user is supplied with the basic
      clinical information and a set of representative pictures of the histological
      specimens. In some cases radiographs and CT-images are available. During the
      consultation session both routine and special staining methods are available on
      request. If the user proposes a wrong diagnosis the system offers a commentary.
      The presented cases are part of a teaching series developed for residents in
      neuropathology.

PMID- 8287630
TI  - Carrier erythrocytes. Clinical pharmacokinetic considerations.

PMID- 8287631
TI  - Clinical pharmacokinetics of sparfloxacin.
AB  - Sparfloxacin is a recently developed fluoroquinolone. The drug has shown potent
      antimicrobial activity against a wide range of Gram-positive and Gram-negative
      bacteria, glucose non-fermenters, anaerobes, Legionella spp., Mycoplasma spp.,
      Chlamydia spp. and Mycobacterium spp. Methicillin-resistant Staphylococcus aureus
      is also susceptible to sparfloxacin. Plasma sparfloxacin concentrations reach a
      peak (Cmax) of approximately 0.7 mg/L at 3 to 5 hours after a 200mg oral dose.
      This is followed by a monophasic slow decrease, with an elimination half-life
      (t1/2) of 15 to 20 hours. The Cmax and area under the plasma concentration-time
      curve show dose-related increases. Food intake does not affect the absorption and
      pharmacokinetics of sparfloxacin. Sparfloxacin binds weakly to plasma protein
      (37%), and exhibits excellent tissue distribution and effective penetration into
      extracellular fluids. Concentrations of the drug in most tissues are similar to,
      or higher than, concomitant plasma concentrations. Sparfloxacin distributes
      slightly into cerebrospinal fluid. The drug is metabolised to a glucuronide. The
      urinary excretion of the unchanged drug accounts for 10 to 14% of the given dose.
      The ratio of Cmax values after multiple and single oral doses is 1.3 to 1.4, but
      other pharmacokinetic parameters of sparfloxacin are not influenced by multiple
      doses. Even in patients with severe renal failure, no significant prolongation of
      the half-life is observed after oral administration. Sparfloxacin appears
      unlikely to affect the pharmacokinetics of theophylline. Antacids containing
      aluminium hydroxide reduce the oral bioavailability of sparfloxacin by 25 to 35%.
      Probenecid does not affect sparfloxacin pharmacokinetics. The pharmacokinetic
      properties of sparfloxacin allow once-daily administration in the treatment of
      various infections.

PMID- 8287632
TI  - Azithromycin clinical pharmacokinetics.
AB  - Azalide antibiotics, of which azithromycin is the first demonstrated, have
      different pharmacokinetics from other antibiotics currently used. The
      bioavailability of the drug is approximately 37%. Extensive and rapid
      distribution from serum into the intracellular compartments is followed by rapid
      distribution to the tissues. Tissue concentrations exceed serum concentrations by
      up to 100-fold following a single azithromycin 500mg dose. Concentration of the
      drug within phagocytes aids in its ability to combat infections. High
      concentrations of azithromycin are found in the tonsil, lung, prostate, lymph
      nodes and liver, with only small concentrations found in fat and muscle. A 500mg
      dose on day 1, followed by 250mg daily on days 2 to 5, has been demonstrated to
      maintain azithromycin concentrations at sites of infection and continues to be
      effective for several days after administration has ceased. The pharmacokinetics
      of azithromycin make it a drug with diverse therapeutic applications.

PMID- 8287634
TI  - Pharmacokinetics and electrophysiological effects of intravenous ajmaline.
AB  - The pharmacokinetics of ajmaline were studied in 10 patients with suspected
      paroxysmal atrioventricular block who received a 1 mg/kg intravenous dose over 2
      minutes for diagnostic purposes (ajmaline test). Plasma concentration decay
      followed a triexponential time course with a final half-life much longer (7.3 +/-
      3.6 hours) than that previously found by other investigators (about 15 minutes).
      Mean total plasma clearance and renal clearance were 9.76 ml/min/kg and 0.028
      ml/min/kg, respectively. Although most of the dose was eliminated through the
      extrarenal route (only 3.5% of the intravenous dose was recovered in urine), no
      fluorescent metabolites could be detected either in plasma or urine. The steady
      state volume of distribution averaged 6.17 L/kg, and plasma protein binding
      ranged between 29 and 46%. Three patients developed a transient atrioventricular
      block after ajmaline administration. In the remainder, the drug prolonged atrio
      His bundle (AH interval), His bundle-ventricular (HV interval) and
      intraventricular (QRS interval) conduction times. Corrected ventricular
      repolarisation time (QTc interval) showed less marked changes, which were
      biphasic at times. The mean maximum ajmaline-induced increase in HV interval was
      98%, in QRS was 58%, in AH was 30%, and in QTc was 17%. In most cases the time
      course of electrocardiographic changes lagged behind that of plasma
      concentrations, suggesting a delayed equilibrium of plasma concentrations with
      the site of action (hysteresis). Despite that, the pharmacokinetic
      pharmacodynamic model, which accounted for hysteresis, failed to fit the
      experimental data adequately.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287633
TI  - Clinical pharmacokinetics of octreotide. Therapeutic applications in patients
      with pituitary tumours.
AB  - Among somatostatin analogues, octreotide is the most extensively studied. Its
      pharmacodynamic properties are similar to those of somatostatin, with a wide
      spectrum of inhibitory effects on anterior pituitary function, pancreas and gut
      endocrine secretions, and gastrointestinal functions. Compared with the
      somatostatin, octreotide is highly resistant to enzymatic degradation and has a
      prolonged plasma half-life of about 100 minutes in humans, allowing its use in
      the long term treatment of various pathological conditions. Differential effects
      of octreotide on endocrine secretions such as growth hormone (GH) and insulin in
      healthy volunteers, as well as variable efficacy in the treatment of endocrine
      tumours, may relate to the distribution of somatostatin receptor subtypes. The
      volume of distribution of octreotide ranges from 18 to 30L. Calculated serum
      distribution half-life ranges from 72 to 98 minutes. In blood, octreotide is
      mainly distributed in the plasma, 65% being bound to lipoproteins. After
      subcutaneous injection, absorption appears rapid and complete and bioavailability
      is about 100%. Mean peak plasma concentrations are between 2 and 4 micrograms/L
      in patients receiving 50 to 100 micrograms. Peak concentrations are reached
      within 20 to 30 minutes and are 20 to 40% of corresponding values after
      intravenous injection. Peak concentrations and values for areas under the plasma
      concentration-time curve linearly correlate with the dosage. The elimination half
      life is about 90 to 110 minutes. Total clearance in healthy individuals is about
      160 ml/min (9.6 L/h). Hepatic metabolism of octreotide is extensive (30 to 40%)
      and about 11 to 20% of the dose is excreted unchanged in the urine. Among
      pituitary tumours, GH- and thyrotrophin-secreting adenomas are the most sensitive
      to octreotide. Octreotide has been widely used in the treatment of acromegaly. 50
      to 80% of the patients respond to daily multiple subcutaneous injections with
      insulin-like growth factor-1 (IGF1) levels being normalised in about 40 to 50% of
      them. Neither desensitisation with long term therapy nor rebound phenomena after
      octreotide withdrawal have been noticed in these studies. Even in patients with
      partial response, clinical symptoms improved. Octreotide daily dosages needed to
      achieve optimum responses may vary greatly from one patient to another. In a
      minority of patients complete resistance to octreotide was observed and was not
      always related to the absence of somatostatin receptors in the tumour. The wide
      spectrum of effects of octreotide in humans accounts for adverse effects seen
      during long term treatment, primarily cholelithiasis. Other modes of
      administration are efficient.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8287636
TI  - Culture techniques and their applications to studies of vascular smooth muscle.

PMID- 8287635
TI  - Multiple-dose pharmacokinetics of pefloxacin in patients with hepatocellular
      deficiency.
AB  - Multiple-dose pharmacokinetics of pefloxacin were evaluated in 25 patients with
      hepatocellular insufficiency. The severity of liver disease was graded A, B or C
      according to the Child-Pugh classification. Pharmacokinetic parameters evaluated
      in patients on day 1 of treatment were compared with those computed in 11 healthy
      volunteers (the control group) after a single dose. Blood samples were taken at
      frequent intervals after drug administration and assayed by high performance
      liquid chromatography. The mean age of patients with liver impairment was
      slightly greater (59.5 years, range 33 to 81 years) than that of the control
      group (46.7 years, range 42 to 51 years). In the patients with liver disease, the
      mean (+/- SD) half-life of elimination, although highly variable, was
      significantly longer (46.3 +/- 42.5 hours) than in the control group (11.3 +/-
      3.5 hours, p < 0.001). The total clearance was significantly decreased (1.76 +/-
      1.31 L/h vs 6.03 +/- 2.99 L/h in the control group). In groups B and C of the
      Child-Pugh classification, total body clearance was about 30% of normal values.
      Elimination half-life increased by 200% in group B and 373% in group C compared
      with values in healthy volunteers. Intergroup differences (group B vs group C of
      the Child-Pugh classification) were not statistically significant. The minimum
      concentrations inhibiting 90% of Gram-negative strains (MIC90) were exceeded by
      plasma pefloxacin concentrations throughout treatment. For most patients, trough
      plasma concentrations were above 2 mg/L and peak plasma concentrations averaged
      8.5 mg/L. Large inter- and intraindividual variations in the elimination half
      life, total clearance and volume of distribution were observed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8287637
TI  - CD45RA+ T cells: not simple virgins.
AB  - 1. The T cells which mediate immunological memory remain elusive. Identification
      of such cells would open the door to increasingly specific immunotherapy in areas
      such as transplantation and autoimmunity. 2. Over the last few years attempts
      have been made to identify phenotypic markers which can distinguish naive or
      virgin T cells from primed or memory ones. In humans, great hopes were raised
      when it was shown that the level of expression of the higher-molecular-mass
      isoforms (CD45RA) of the tyrosine phosphatase, CD45, correlated with previous
      exposure to antigen. 4. However, our studies in the mouse and more recent studies
      in rat and human suggest that expression of CD45RA more closely correlates with
      the state of responsiveness of the T cell. 5. Thus, with time, activated/memory T
      cells return to a state of quiescence or hypo-responsiveness and express high
      levels of CD45RA. Hence, not all CD45RA+ T cells are virgins.

PMID- 8287638
TI  - A novel antiserum specific to apolipoprotein B-48: application in the
      investigation of postprandial lipidaemia in humans.
AB  - 1. Apolipoprotein B-48, the transport protein for chylomicrons, is identical with
      apolipoprotein B-100 for the first 48% of its sequence. No antiserum has yet been
      reported that can recognize apolipoprotein B-48, but not apolipoprotein B-100. 2.
      In the present study an antiserum was raised to the C-terminal sequence of
      apolipoprotein B-48, using specific chemical reactions to ensure that the charged
      carboxyl group of the C-terminal isoleucine residue was free. In a Western blot
      the antiserum was shown to bind to a protein band having the characteristics of
      apolipoprotein B-48, but not to apolipoprotein B-100. 3. In the early evening 11
      subjects were given a test meal which contained 40 g of mixed oil and retinyl
      palmitate. Blood samples were collected over 9 h. Chylomicron-enriched fractions
      were prepared and analysed for triacylglycerol, retinyl palmitate and
      apolipoprotein B-48, the latter after separation using SDS/PAGE and visualization
      by chemiluminescence on a Western blot. Both triacylglycerol and apolipoprotein B
      48 showed an early peak at 1 h, which was not seen with retinyl palmitate. All
      three substances gave a broader peak between 5 and 6 h postprandially. Retinyl
      palmitate concentrations declined rapidly during the late (6-9 h) postprandial
      period, but apolipoprotein B-48 concentrations remained elevated. 4. This study
      has shown that an antiserum has been produced which is specific for
      apolipoprotein B-48. This has enabled measurement of postprandial concentrations
      of the protein that revealed features of chylomicron metabolism which have not
      been reported previously.

PMID- 8287639
TI  - Insulin resistance of stress: sites and mechanisms.
AB  - 1. Stress is associated with a severe, yet reversible, form of insulin
      resistance. The aim of this study was to quantify the kinetics of insulin action
      (sensitivity and responsiveness) on intermediary metabolism during post-surgical
      stress. 2. We studied nine patients 6-8 h after major uncomplicated surgery, and
      eight healthy subjects matched for age, weight, glucose tolerance and duration of
      fast. A three-step isoglycaemic insulin clamp was combined with indirect
      calorimetry, [6-3H]glucose infusion and the forearm technique. 3. The following
      significant (P < 0.05 or less) abnormalities were found in the patients. Hepatic
      glucose production was higher at baseline, and less suppressed by insulin. Whole
      body glucose disposal was impaired at all insulin doses (by 33-60%). Glucose
      oxidation was depressed throughout the dose range but its increments in response
      to insulin were normal. In contrast, non-oxidative glucose disposal was
      essentially unresponsive. At all insulin levels, forearm glucose extraction was
      markedly depressed and forearm lactate release was in excess of concurrent
      glucose uptake, suggesting ongoing glycogenolysis despite insulin. Total
      lipolysis (plasma free fatty acid and glycerol levels) promptly responded to
      insulin but remained higher than in the control subjects throughout. In the
      forearm, even the highest insulin dose could not suppress net free fatty acid and
      glycerol release. Total lipid oxidation was increased throughout the insulin
      range, and calculated direct free fatty acid (as opposed to plasma free fatty
      acid) oxidation was virtually unaffected by insulin. Protein oxidation was
      slightly (35%) increased, but was suppressed normally in response to insulin.
      Energy expenditure was 20% higher at baseline, and failed to rise with insulin.
      Arterial blood pH values were consistently (if slightly) lower, and net forearm
      proton release was higher, both at baseline and during insulin infusion. 4. Post
      surgical insulin resistance is characterized by normal sensitivity but decreased
      responsiveness of glucose oxidation, lipolysis and plasma free fatty acid
      oxidation, whereas glycogen synthesis and direct free fatty acid oxidation are
      virtually unresponsive. For both glucose and lipid metabolism, the insulin
      resistance is particularly severe in forearm tissues, in which mild metabolic
      acidosis may play an additional role.

PMID- 8287640
TI  - Effect of acute mild hypoglycaemia on counterregulatory responses to moderate
      hypoglycaemia induced immediately afterwards in healthy men.
AB  - 1. This study was designed to determine whether a 1 h period of mild
      hypoglycaemia (3.3 or 3.7 mmol/l) affected the response to an episode of moderate
      hypoglycaemia (2.5 mmol/l) immediately afterwards. 2. Eleven non-obese healthy
      men (age 26 +/- 1 years, mean +/- SEM) underwent three separate 3 h hyper
      insulinaemic glucose clamps in single-blind, random order. On all three
      occasions, blood glucose was 4.5 mmol/l for the first hour, and on a control
      visit was maintained at this level for the second hour. In the other two visits,
      blood glucose was lowered to 3.7 or 3.3 mmol/l during the second hour. In the
      third hour, blood glucose was lowered to 2.5 mmol/l on all three visits. 3. In
      the second hour, adrenaline rose significantly (P < 0.05, analysis of variance)
      with a blood glucose of 3.3 and 3.7 mmol/l, as did cortisol and heart rate at 3.3
      mmol/l, but glucagon, prolactin, sweating rate, symptom score and blood pressure
      were the same during the second hour on all three visits. 4. In the final hour at
      2.5 mmol/l, there were no differences in adrenaline, noradrenaline, glucagon,
      prolactin, cortisol, symptom score, heart rate, blood pressure or sweating rate.
      5. Thus, the overall magnitude of hormonal responses to moderate hypoglycaemia
      (2.5 mmol/l) are not modified by exposure to mild hypoglycaemia (3.3 or 3.7
      mmol/l) for 1 h immediately beforehand.

PMID- 8287641
TI  - Antecedent insulin level and pattern of induction of acute hypoglycaemia do not
      affect subsequent counterregulatory responses in healthy subjects.
AB  - 1. This study was designed to determine whether the duration and pattern of prior
      insulin exposure modulate the symptomatic and counterregulatory responses to
      hypoglycaemia. 2. Ten healthy non-obese subjects (five males/five females age 25
      +/- 1 years, mean +/- SEM) were made hypoglycaemic in three ways: (i) a
      hyperinsulinaemic (60 m-units min-1 m-2; plasma insulin concentration 95 m
      units/I) clamp, with 1 h of euglycaemia, blood glucose level 4.5 mmol/l, followed
      by 30 min of hypoglycaemia, at a stable glucose nadir of 2.0 mmol/l (i.e.
      euglycaemic then hypoglycaemic clamp: E + HC); (ii) an identical hypoglycaemic
      clamp without preceding hyperinsulinaemic euglycaemia (i.e. a hypoglycaemic
      clamp: HC); (iii) insulin infusion only, discontinued at a blood glucose level of
      3.0 mmol/l (II). Blood glucose level reached the same nadir as on E + HC and HC,
      and did not fall further. At the glucose nadir, and 15 and 30 min after, the
      plasma insulin concentration was 23, 7 and 4 m-units/l, respectively, on the II
      visit. 3. At the glucose nadir, plasma glucagon level, plasma adrenaline level,
      sweating rate, heart rate, blood pressure, and overall and individual symptom
      scores (using visual analogue scales) were the same on E + HC, HC and II. 4.
      There were no significant differences in neurohormonal response between E+HC and
      HC, but more subjects felt hypoglycaemic on E + HC on arrival at the glucose
      nadir (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287642
TI  - Free-radical activity after reperfusion in diabetic and non-diabetic patients
      with acute myocardial infarction.
AB  - 1. Oxygen-derived free radicals have been implicated in reperfusion injury after
      thrombolytic therapy in acute myocardial infarction. To test the hypothesis that
      diabetic patients may have increased oxidative stress which may lead to increased
      reperfusion damage and thereby contribute to a poorer outcome in these patients,
      we measured two indices of free-radical activity, diene conjugate molar ratios as
      an index of lipid isomerization and thiobarbituric acid-reactive material as an
      index of lipid peroxidation, in 66 non-diabetic and 26 diabetic patients admitted
      with acute myocardial infarction who received thrombolytic therapy and in whom
      reperfusion was assessed using early time to peak creatine kinase-MB isoenzyme
      release. 2. Baseline diene conjugate molar ratios or thiobarbituric acid
      reactivity did not differ significantly between diabetic and non-diabetic
      patients (1.97 +/- 0.98 versus 2.16 +/- 1.34; not significant and 2.10 +/- 0.60
      versus 1.99 +/- 0.73 mumol/l; not significant). In patients with enzymic evidence
      of reperfusion (i.e. time to peak enzyme release < or = 12 h) diene conjugate
      molar ratios peaked at 6 h compared with 12h in those with unsuccessful
      reperfusion (i.e. time to peak enzyme release > 12 h). In patients with unstable
      angina the maximum increase in the diene conjugate molar ratios was significantly
      less than in patients with acute myocardial infarction (6.80 +/- 12.3 versus
      15.82 +/- 22.55%; P = 0.035). There was a significant fall in thiobarbituric acid
      reactivity at 24 h in patients with enzymic evidence of reperfusion (P = 0.017).
      There were no major differences in these rises and falls between diabetic and non
      diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287643
TI  - Relationship between markers of endothelial dysfunction, oxidant injury and
      tubular damage in patients with insulin-dependent diabetes mellitus.
AB  - 1. Diabetic nephropathy is a serious microvascular complication in patients with
      insulin-dependent diabetes mellitus, resulting in end-stage renal disease in 30
      45% of such patients. Despite intensive investigation, the pathophysiology of
      diabetic renal disease has not been fully elucidated. However, several clinical
      and experimental studies have suggested that endothelial dysfunction and free
      radical activity may be important factors. 2. Forty normotensive patients with
      insulin-dependent diabetes mellitus of between 10 and 20 years duration with
      persistent normoalbuminuria (albumin excretion < 30 mg/day) and normal renal
      function were investigated for markers of endothelial dysfunction (plasma von
      Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme
      activity), free oxygen radical generation (erythrocytic superoxide dismutase and
      glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular
      proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding
      protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine
      aminopeptidase) were also measured. 3. Patients were divided into two groups.
      Group 1 comprised 21 patients with elevated markers of endothelial dysfunction,
      and group 2 comprised 19 patients with normal levels of plasma von Willebrand
      factor, soluble thrombomodulin and angiotensin-converting enzyme activity. Thirty
      eight healthy subjects matched for age and sex acted as controls. 4. Groups 1 and
      2 were similar in age, sex, body weight, duration of diabetes mellitus and recent
      glycaemic control. Serum cholesterol, serum creatinine and glomerular proteinuria
      were similar in the three groups. Group 1 patients had significantly increased
      oxidant injury, tubular enzymuria and proteinuria compared with group 2 patients
      and control subjects (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287644
TI  - Tumour necrosis factor-alpha, resting energy expenditure and cachexia in cystic
      fibrosis.
AB  - 1. We investigated the relationship between circulating tumour necrosis factor
      alpha concentrations, resting energy expenditure, cachexia and altered
      intermediary metabolism in patients with cystic fibrosis and chronic pulmonary
      infection. 2. Twenty adult patients with cystic fibrosis and chronic bronchial
      sepsis covering a spectrum of severity of lung disease (forced expiratory volume
      in 1 s 30-100% of predicted) were compared with 10 age matched, healthy, non
      cystic fibrosis subjects. 3. Circulating tumour necrosis factor-alpha, C-reactive
      protein and neutrophil elastase-alpha 1-antiproteinase complex concentrations
      were determined simultaneously with glycerol, non-esterified fatty acids,
      catecholamines, anthropometric indices and resting energy expenditure (ventilated
      hood method). 4. Weight, body mass index and arm muscle mass were reduced in
      patients with cystic fibrosis compared with healthy control subjects (P < 0.01),
      whereas mean resting energy expenditure was increased [121 versus 101% predicted,
      mean difference 19.2% (95% confidence interval 11.0-27.4%), P < 0.001].
      Circulating concentrations of glycerol (P < 0.01), non-esterified fatty acids (P
      < 0.01), adrenaline (P < 0.05), tumour necrosis factor-alpha, C-reactive protein
      and neutrophil elastase-alpha 1-antiproteinase complex (P < 0.01) were increased
      in patients compared with control subjects [tumour necrosis factor-alpha 96.9
      versus 24.7 pg/ml, mean difference 72.2 pg/ml [95% confidence interval 27.7-116.7
      pg/ml), P < 0.001]. Resting energy expenditure was significantly related to
      tumour necrosis factor-alpha levels and forced expiratory volume in 1 s. 5. In
      patients with cystic fibrosis and chronic pulmonary sepsis changes in resting
      energy expenditure, body composition and intermediary metabolism are consistent
      with the systemic effects of the host inflammatory response, which may be
      responsible for cachexia in adult patients. In particular these changes are
      consistent with the action of tumour necrosis factor-alpha, which was detected in
      the circulation during a period of apparent clinical stability.

PMID- 8287645
TI  - Induction of enhanced responsiveness of human articular chondrocytes to
      extracellular ATP by tumour necrosis factor-alpha.
AB  - 1. We have observed previously that extracellular ATP acting at P2-purinoceptors
      promotes the production of prostaglandin E2 by human articular chondrocytes, and
      that this response is enhanced synergistically by interleukin-1 beta. Since other
      cytokines that influence the metabolism of articular cartilage may have a similar
      effect, we have investigated whether tumour necrosis factor-alpha also modulates
      the stimulation of the production of prostaglandin E2 in these cells by ATP. 2.
      Tumour necrosis factor-alpha enhanced the response of cultured human articular
      chrondrocytes to a maximally stimulating concentration of ATP (100 mumol/l). This
      effect was present when the cells were co-incubated with tumour necrosis factor
      alpha and ATP for 4 h, was augmented when the cells were also preincubated with
      the cytokine for 24 h, and remained constant or decline on extending the
      preincubation period to 72 h. The enhancement of responsiveness to ATP by tumour
      necrosis factor-alpha was dose-dependent, and the minimum effective concentration
      (6 pmol/l) did not consistently increase prostaglandin E2 production when the
      cytokine was tested alone. The presence of tumour necrosis factor-alpha during
      the incubation with ATP was required for maximum enhancement of the response.
      Tumour necrosis factor-alpha did not alter the minimum concentration of ATP that
      stimulated production of prostaglandin E2. 3. Cytokines such as interleukin-1 and
      tumour necrosis factor-alpha are involved in the pathogenesis of some forms of
      arthritis, and these data provide additional evidence that their actions in
      articular cartilage may be modulated by other agents which originate from
      chondrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287646
TI  - Impact of treatment with acetylsalicylic acid on the proaggregatory effects of
      adrenaline in vitro in patients with stable angina pectoris: influence of the
      anticoagulant.
AB  - 1. The impact of oral acetylsalicylic acid treatment on the enhancing effect of
      adrenaline on platelet aggregation in vitro was investigated in patients with
      stable angina pectoris. In addition, the influence of different anticoagulants
      (i.e. hirudin and citrate) on platelet aggregation in vitro was compared. 2.
      Eighty-four patients with stable angina pectoris were studied. Sixteen patients
      were on acetylsalicylic acid treatment (150-250 mg daily), whereas 68 patients
      were free from acetylsalicylic acid. Platelet-rich-plasma was prepared from
      citrate- or hirudin-anticoagulated blood. The EC50 (i.e. the concentration of
      agonist required to produce half-maximal aggregation) for the ADP-induced extent
      of aggregation was determined. Thereafter the enhancing effect of adrenaline (10
      and 50 nmol/l) on ADP-induced aggregation (at EC50) was investigated. 3. In the
      patients with angina, acetylsalicylic acid caused the expected effects on ADP
      induced platelet responses. Adrenaline significantly enhanced both the extent of
      aggregation and the initial rate of aggregation (primary aggregation),
      irrespective of the anticoagulant used. In acetylsalicylic acid-treated patients
      (citrated platelet-rich plasma) the extent of aggregation was partly inhibited,
      but no significant effect on the rate of aggregation could be observed. 4. A
      comparative substudy of the anticoagulants in healthy subjects (n = 8) showed
      that both the aggregating effect of ADP per se and the enhancing effect of
      adrenaline on ADP-induced aggregation (at EC50) were less influenced by
      acetylsalicylic acid when evaluated in hirudinized platelet-rich plasma (i.e.
      with physiological levels of extracellular calcium) as compared with citrated
      platelet-rich plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287647
TI  - Cell membrane microviscosity and Ca(2+)-Mg(2+)-ATPase activity do not contribute
      to hypertension in the spontaneously hypertensive rat model.
AB  - 1. The relationships between systolic blood pressure and altered erythrocyte
      Ca(2+)-Mg(2+)-ATPase activity and membrane microviscosity were assessed in
      membranes prepared from 20-week-old female Wistar-Kyoto normotensive and
      spontaneously hypertensive rats obtained from two different sources (Charles
      River and Harlan OLAC) and a second filial (F2) generation derived from a cross
      between Wistar-Kyoto rats and spontaneously hypertensive rats from one source
      (Charles River). 2. Spontaneously hypertensive rats from both sources had
      systolic blood pressures significantly higher than those of Wistar-Kyoto animals
      (P < 0.05; 151 +/- 4 and 110 +/- 3 mmHg, Charles River; 155 +/- 4 and 122 +/- 4
      mmHg, Harlan OLAC). The systolic blood pressures for the F2 rat population ranged
      between 73 and 168 mmHg. 3. Ca(2+)-Mg(2+)-ATPase activity was measured as ATP
      dependent 45Ca2+ uptake into inside-out vesicles and microviscosity assessed by
      the measurement of polarization anisotropy of membrane incorporated fluorescent
      probes including 1,6-diphenyl-1,3,5-hexatriene, trimethylamino-1,6-diphenyl-1,3,5
      hexatriene and a series of anthroyloxy fatty acids. 4. Contrary to previous
      studies, no relationship between adult systolic blood pressure and erythrocyte
      Ca(2+)-Mg(2+)-ATPase activity or general or localized membrane microviscosity was
      indicated by the comparison of spontaneously hypertensive and Wistar-Kyoto
      animals or in the analysis of the F2 rat population. 5. These results suggest
      that Ca(2+)-Mg(2+)-ATPase activity and membrane microviscosity are causally
      unrelated to hypertension in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287648
TI  - Rat renal, aortic and pulmonary endothelin-I receptors: effects of changes in
      sodium and water intake.
AB  - 1. In the present study we investigated, first, the effects of high Na+ intake
      and, second, the effects of water deprivation on plasma endothelin-1
      concentration and urinary endothelin-1 excretion and on endothelin receptors in
      membranes of renal glomeruli and papillae and of aortic smooth muscle and lung
      tissue from 32 female Sprague-Dawley rats. 2. After 5 weeks of high Na+ intake (n
      = 8) urinary Na+ excretion was 10.5 +/- 1.3 compared with 1.6 +/- 0.2 mmol/24 h
      in controls. Body weight, plasma osmolarity, plasma endothelin-1 concentration
      (23 +/- 6 versus 28 +/- 3 fmol/ml) and urinary endothelin-1 excretion (6.1 +/-
      1.3 versus 4.7 +/- 0.3 pmol/24 h) remained unchanged. 3. The characteristics of
      endothelin-1 receptors in glomeruli, papillae, aortic smooth muscle and lung
      tissue from salt-loaded rats were not different from those of controls. 4. After
      48 h water deprivation (n = 8) body weight had decreased, whereas packed cell
      volume and plasma and urine osmolarities had increased compared with controls (n
      = 8) (P < 0.05). Plasma endothelin-1 concentration (40 +/- 6 versus 21 +/- 2
      fmol/ml) was higher (P < 0.01) and urinary endothelin-1 excretion (1.0 +/- 0.2
      versus 2.8 +/- 0.3 pmol/24 h) was lower than in controls (P < 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8287649
TI  - Control of sodium excretion in patients with cranial diabetes insipidus
      maintained on desamino-[8-D-arginine]vasopressin.
AB  - 1. We have studied the response of six patients with cranial diabetes insipidus
      and six age-matched control subjects to dietary sodium restriction during
      constant administration of the synthetic vasopressin analogue desamino-[8-D
      arginine]vasopressin. 2. Urine flow increased on the first low salt day in the
      normal control subjects but not in the patients with cranial diabetes insipidus.
      Body weight fell 1.35 kg in the control subjects but was constant in the patients
      with cranial diabetes insipidus. 3. Urinary sodium excretion fell at the same
      rate in both groups. Diurnal variation of urinary sodium excretion and creatinine
      clearance was present in the control subjects but not in the patients with
      cranial diabetes insipidus. 4. Changes in plasma sodium concentration and
      osmolality were similar. Plasma protein concentration increased more in the
      control subjects (from 69.1 +/- 1.5 to 73 +/- 1.2 versus from 71.7 +/- 1 to 73.2
      +/- 1.1 milligrams). The responses of plasma atrial natriuretic peptide, plasma
      renin activity and salivary aldosterone concentration were similar between the
      two groups. Salivary aldosterone concentration levels were consistently higher in
      the patients with cranial diabetes insipidus. 5. We confirm that the low salt
      diuresis is triggered by release from the antidiuretic activity of arginine
      vasopressin. In the patients with cranial diabetes insipidus extracellular fluid
      osmoregulation appeared to be achieved by the movement of water out of and sodium
      into the extracellular fluid. 6. Absent posterior pituitary function and
      hypothalamic disturbances did not alter renal sodium conservation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8287650
TI  - A comparison of the renal and neuroendocrine effects of two 5-hydroxytryptamine
      renal prodrugs in normal man.
AB  - 1. The effects of 1 h intravenous infusions of equimolar amounts (45 nmol min-1
      kg-1) of two putative 5-hydroxytryptamine renal prodrugs, 5-hydroxy-L-tryptophan
      and gamma-L-glutamyl-5-hydroxy-L-tryptophan, were investigated in a randomized,
      placebo-controlled, cross-over study in nine healthy male subjects. 2. Cumulative
      urinary 5-hydroxytryptamine excretion over the 3 h observation period rose by
      about 370-fold after 5-hydroxy-L-tryptophan and 390-fold after gamma-L-glutamyl-5
      hydroxy-L-tryptophan when compared with placebo infusion. Urinary 5-hydroxy-L
      tryptophan excretion was three times higher after administration of gamma-L
      glutamyl-5-hydroxy-L-tryptophan than after 5-hydroxy-L-tryptophan infusion.
      Urinary 5-hydroxyindole-3-acetic acid excretion after 5-hydroxy-L-tryptophan
      infusion was significantly greater than that after gamma-L-glutamyl-5-hydroxy-L
      tryptophan administration. Urinary dopamine excretion was not affected by either
      compound when compared with placebo. 3. 5-Hydroxy-L-tryptophan significantly
      reduced urine flow rate and urinary sodium excretion. gamma-L-Glutamyl-5-hydroxy
      L-tryptophan was antinatriuretic but did not affect urine output. These changes
      occurred without significant alterations in effective renal plasma flow and
      glomerular filtration rate. 4. Both 5-hydroxy-L-tryptophan and gamma-L-glutamyl-5
      hydroxy-L-tryptophan significantly increased plasma aldosterone concentration
      without a concomitant rise in plasma renin activity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8287651
TI  - Sulphide impairment of substrate oxidation in rat colonocytes: a biochemical
      basis for ulcerative colitis?
AB  - 1. Isolated colonic epithelial cells of the rat were incubated for 40 min with [6
      14C]glucose and n-[1-14C]butyrate in the presence of 0.1-2.0 mmol/l NaHS, a
      concentration range found in the human colon. Metabolic products, 14CO2,
      acetoacetate, beta-hydroxybutyrate and lactate, were measured and injury to cells
      was judged by diminished production of metabolites. 2. Oxidation of n-butyrate to
      CO2 and acetoacetate was reduced at 0.1 and 0.5 mmol/l NaHS, whereas glucose
      oxidation remained unimpaired. At 1.0-2.0 mmol/l NaHS, n-butyrate and glucose
      oxidation were dose-dependently reduced at the same rate. 3. To bypass short
      chain acyl-CoA dehydrogenase activity necessary for butyrate oxidation,
      ketogenesis from crotonate was measured in the presence of 1.0 mmol/l NaHS.
      Suppression by sulphide of ketogenesis from crotonate (-10.5 +/- 6.1%) compared
      with control conditions was not significant, whereas suppression of ketogenesis
      from n-butyrate (-36.00 +/- 5.14%) was significant (P = < 0.01). Inhibition of
      FAD-linked oxidation was more affected by NaHS than was NAD-linked oxidation. 4.
      L-Methionine (5.0 mmol/l) significantly redressed the impaired beta-oxidation
      induced by NaHS. Methionine equally improved CO2 and ketone body production,
      suggesting a global reversal of the action of sulphide. 5. Sulphide-induced
      oxidative changes closely mirror the impairment of beta-oxidation observed in
      colonocytes of patients with ulcerative colitis. A hypothesis for the disease
      process of ulcerative colitis is that sulphides may form persulphides with
      butyryl-CoA, which would inhibit cellular short-chain acyl-CoA deHydrogenase and
      beta-oxidation to induce an energy-deficiency state in colonocytes and mucosal
      inflammation.

PMID- 8287652
TI  - Modulation of small-intestinal secretion and absorption in chronic vitamin E
      deficiency: studies in rat jejunum in vitro.
AB  - 1. A vicious cycle of malabsorption and malnutrition has been implicated in the
      pathogenesis of protracted diarrhoeal disease in infancy. Vitamin E deficiency is
      common in malnourished infants with protracted diarrhoea. We have studied the
      effects of chronic vitamin E deficiency on small-intestinal secretion and
      absorption in the rat. 2. Weanling rats were fed vitamin E-sufficient or 
      deficient diets for 21 weeks. Jejunal function was studied in vitro in an Ussing
      chamber after this period. 3. Steady-state isotopic flux experiments in
      unstimulated tissues demonstrated net Na+ and Cl- secretion in vitamin E
      deficient jejuna but net Na+ and Cl- absorption in vitamin E-sufficient jejuna.
      4. Basal intestinal short-circuit current was the same in both groups. 5. Cyclic
      nucleotide and maximal non-neuronal acetylcholine-mediated electrogenic secretion
      were increased in vitamin E-deficient jejuna. 6. Exogenous 5-hydroxytryptamine
      (serotonin) induced a smaller increment in electrogenic secretion in vitamin E
      deficient jejuna. 7. Vitamin E-deficient jejuna were less responsive to exogenous
      noradrenaline, resulting in a smaller alpha 2-adrenergic-mediated decrease in
      intestinal short-circuit current. 8. Fasting for 72h produced a greater increment
      in intestinal short-circuit current in vitamin E-deficient jejuna. 9. Chronic
      vitamin E deficiency is prosecretory in the small intestine and may predispose to
      the perpetuation of protracted diarrhoeal diseases.

PMID- 8287653
TI  - Physiological determinants of inspiratory effort sensation during CO2 rebreathing
      in normal subjects.
AB  - 1. The physiological basis of inspiratory effort sensation remains uncertain.
      Previous studies have suggested that pleural pressure, rather than inspiratory
      muscle fatigue, is the principal determinant of inspiratory effort sensation.
      However, only a limited range of inspiratory flows and breathing patterns have
      been examined. We suspected that inspiratory effort sensation was related to the
      inspiratory muscle tension-time index developed whatever the breathing pattern or
      load, and that this might explain the additional rise in sensation seen with
      hypercapnia. 2. To investigate this we measured hypercapnic rebreathing responses
      in seven normal subjects (six males, age range 21-38 years) with and without an
      inspiratory resistive load of 10 cm H2O. Pleural and transdiaphragmatic
      pressures, mouth occlusion pressure and breathing pattern were measured.
      Diaphragmatic and ribcage tension-time indices were calculated from these data.
      Inspiratory effort sensation was recorded using a Borg scale at 30s intervals
      during each rebreathing run. 3. Breathing pattern and inspiratory pressure
      partitioning were unrelated to changes in inspiratory effort sensation during
      hypercapnia. Tension-time indices reached pre-fatiguing levels during both free
      breathing and inspiratory resistive loading. 4. Stepwise multiple regression
      analysis using pooled mechanical, chemical and breathing pattern variables showed
      that pleural pressure was more closely related to inspiratory effort sensation
      than was transdiaphragmatic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287654
TI  - Extracellular volume expansion inhibits antidiuretic hormone increase during
      positive end-expiratory pressure in conscious dogs.
AB  - 1. This study in conscious dogs examined the effects of extracellular volume
      expansion on plasma antidiuretic hormone, atrial natriuretic peptide and
      aldosterone concentrations, plasma renin activity, and haemodynamic and renal
      responses during controlled mechanical ventilation with 20 cmH2O positive end
      expiratory pressure. 2. Twenty experiments (10 controls, 10 expansion experiments
      with 0.5 ml min-1 kg-1 body weight of a balanced electrolyte solution given
      intravenously throughout) were performed in five trained, conscious,
      tracheotomized dogs over 4 h: first and fourth hour, spontaneous breathing;
      second and third hour, 20 cmH2O positive end-expiratory pressure. 3. In the
      control experiments positive end-expiratory pressure increased plasma
      antidiuretic hormone concentration from 1.4 +/- 0.2 to 10.0 +/- 3.3 pg/ml, plasma
      aldosterone concentration from 113 +/- 19 to 258 +/- 58 pg/ml and heart rate from
      77 +/- 5 to 94 +/- 5 beats/min. Positive end-expiratory pressure did not change
      plasma atrial natriuretic peptide concentration (55 +/- 5 pg/ml), plasma renin
      activity (2.6 +/- 0.4 pmol of angiotensin I h-1 ml-1) and mean arterial pressure
      103 +/- 3 mmHg). 4. In the expansion experiments, positive end-expiratory
      pressure did not change plasma antidiuretic hormone concentration (1.1 +/- 0.1
      pg/ml), plasma aldosterone concentration (25 +/- 2 pg/ml), plasma atrial
      natriuretic peptide concentration (82 +/- 8 pg/ml), plasma renin activity (0.8 +/
      0.15 pmol of angiotensin I h-1 ml-1), heart rate (92 +/- 6 beats/min) and mean
      arterial pressure (111 +/- 4 mmHg). 5. In the control experiments, urine volume,
      sodium excretion and fractional sodium excretion remained in a low range during
      positive end-expiratory pressure, whereas potassium excretion increased.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8287655
TI  - Agonist-induced desensitization of beta-adrenoceptors of bovine bronchial
      epithelial cells.
AB  - 1. Cultured bovine bronchial epithelial cells express a large number of beta
      adrenoceptors of the beta 2 subtype which are coupled to activation of adenylate
      cyclase and synthesis of cyclic AMP. The mechanisms involved in agonist-induced
      desensitization of beta-adrenoceptor function in these cells were investigated.
      2. Preincubation of cells with the beta-adrenoceptor agonist isoprenaline induced
      a rapid desensitization of adenylate cyclase activity stimulated by isoprenaline
      (40% at 30 min) with little or no decrease in forskolin stimulation or in the
      number of beta-adrenoceptors detected by radioligand binding, indicating that
      uncoupling of beta-adrenoceptors from adenylate cyclase had occurred. 3.
      Uncoupling of beta-adrenoceptors from the stimulatory guanine-nucleotide-binding
      protein Gs was indicated by the loss of GTP effects on agonist competition for
      radioligand binding. Results from subcellular fractionation by sucrose density
      gradient centrifugation suggest that rapid internalization or sequestration of
      beta-adrenoceptors occurred along with the desensitization. 4. Preincubation with
      isoprenaline for longer times led to a marked decrease in total receptor number
      (85% at 18 h), indicating that receptor down-regulation also occurs. Recovery of
      receptors after down-regulation was prevented by cycloheximide and by actinomycin
      D, suggesting that degradation of both receptor protein and receptor mRNA may be
      involved in down-regulation.

PMID- 8287656
TI  - Endothelin peptides as local hormones and their roles in health and disease?

PMID- 8287657
TI  - Non-angiotensin effects of angiotensin-converting enzyme inhibitors.

PMID- 8287658
TI  - Role of alpha 2-adrenoceptors and imidazoline-binding sites in the control of
      insulin secretion.

PMID- 8287659
TI  - Indomethacin stimulates basal glucose production in humans without changes in
      concentrations of glucoregulatory hormones.
AB  - 1. To investigate whether indomethacin affects basal glucose production, we
      measured hepatic glucose production in six healthy postabsorptive subjects on two
      occasions: once after administration of indomethacin (150 mg orally) and once
      after administration of placebo. 2. Glucose production was measured by primed,
      continuous infusion of [3-3H]-glucose. 3. Indomethacin administration resulted in
      an increase in glucose production from 10.9 (SEM 0.3) mumol min-1 kg-1 to a
      maximum of 16.5 (SEM 1.6) mumol min-1 kg-1 (P < 0.05) within approximately 1 h,
      whereas in the control experiment glucose production declined gradually (P <
      0.01) (P < 0.05 indomethacin versus control). There were no differences in plasma
      concentrations of insulin, C-peptide and counter-regulatory hormones between the
      two experiments. 4. Since indomethacin administration resulted in an increase in
      glucose production in the absence of any changes in concentrations of
      glucoregulatory hormones, we conclude that indomethacin stimulates hepatic
      glucose production through other mechanisms.

PMID- 8287660
TI  - Inhibition of nitric oxide synthesis in forearm vasculature of insulin-dependent
      diabetic patients: blunted vasoconstriction in patients with microalbuminuria.
AB  - 1. Microalbuminuria is a risk factor for cardiovascular disease in patients with
      insulin-dependent diabetes mellitus, and may be a marker of microvascular
      dysfunction including endothelial damage. The purpose of this study was to
      determine whether vasoconstrictor responses to NG-monomethyl-L-arginine, an
      inhibitor of endothelium-derived relaxing factor/nitric oxide biosynthesis,
      differ between healthy subjects and insulin-dependent patients with or without
      microalbuminuria. 2. Twenty-eight insulin-dependent diabetic patients (14 with
      normal albumin excretion, 14 with microalbuminuria) were studied under
      euglycaemic conditions, together with 14 healthy control subjects. Forearm
      vascular responses to brachial artery infusions of NG-monomethyl-L-arginine,
      sodium nitroprusside (an endothelium-independent nitrovasodilator) and carbachol
      (an endothelium-dependent vasodilator) were determined by strain gauge
      plethysmography. 3. Basal blood flow and vasodilator responses were similar in
      each group. NG-Monomethyl-L-arginine reduced blood flow by 41.3 +/- 2.3% (mean +/
      SEM) in healthy control subjects, 34.0 +/- 3.4% in diabetic patients without
      microalbuminuria and 29.2 +/- 2.0% in diabetic patients with microalbuminuria.
      Diabetic patients differed from healthy subjects (P = 0.005), due to a difference
      between control subjects and microalbuminuric diabetic patients (P < 0.001). NG
      Monomethyl-L-arginine did not influence nitroprusside responses but reduced
      carbachol responses in control subjects and normoalbuminuric diabetic patients
      but not in microalbuminuric diabetic patients. 4. These results provide evidence
      of abnormal endothelium-derived relaxing factor/nitric oxide biosynthesis in
      insulin-dependent diabetic patients with microalbuminuria.

PMID- 8287661
TI  - Occurrence of presyncope in subjects without ventricular innervation.
AB  - 1. To determine whether activation of the left ventricular C-fibre
      mechanoreceptors initiates the vasodepressor reflex that often causes syncope, we
      exposed six orthotopic cardiac transplant patients and six matched, healthy
      control subjects to progressively increasing lower body negative pressure until
      the onset of vasodepressor responses. 2. There was no significant difference (P =
      0.78) between the central hypovolaemia tolerances of the cardiac transplant and
      the control groups. 3. The decrease in systolic blood pressure before the onset
      of vasodepressor reflexes was greater in the cardiac transplant group. The
      cardiac transplant group did not maintain diastolic blood pressure during central
      hypovolaemia. From baseline to the onset of vasodepression, there were no
      differences in leg circumference, forearm blood flow and forearm vascular
      resistance responses between the two groups. 4. We conclude that the left
      ventricular mechanoreceptors may not be the primary afferent trigger for syncope.

PMID- 8287662
TI  - Brisk walking and serum lipoprotein variables in formerly sedentary men aged 42
      59 years.
AB  - 1. The purpose of this study was to examine the influence of brisk walking on
      serum lipoprotein variables. 2. Seventy-two apparently healthy but physically
      inactive men (aged 42-59 years) were recruited. These men were normotensive non
      smokers without a history of dyslipidaemia. Subjects were randomly allocated on a
      2 to 1 basis into either a walking group (n = 48) or a control group (n = 24).
      Walkers followed a self-monitored programme of brisk walking for 1 year, whereas
      control subjects maintained their habitual lifestyle. 3. Treadmill walking tests
      were conducted to examine changes in fitness. Concentrations of serum lipids and
      lipoproteins were determined in fasting subjects. The amount of body fat was
      measured by body density. Circumferences at the waist and hip and skinfold
      thicknesses were used to determine the distribution of body fat. Dietary intakes
      were assessed by weighed food inventories. 4. Seven subjects (six walkers and one
      control subject) dropped out during the study. Walkers did an average of 28 (SEM
      1.4; n = 42) min of brisk walking/day. This improved endurance fitness but did
      not influence serum concentrations of total cholesterol, high-density lipoprotein
      cholesterol, triacylglycerol, apolipoprotein A-1, apolipoprotein B or lipoprotein
      (a). Neither body mass nor the amount of body fat changed, relative to control
      subjects. 5. These data suggest that brisk walking does not modify lipoprotein
      metabolism in normolipidaemic middle-aged men.

PMID- 8287663
TI  - Hydrogen peroxide generation in a model paediatric parenteral amino acid
      solution.
AB  - 1. Parenteral amino acid solutions undergo photooxidation, which may be an
      important factor in total parenteral nutrition-associated hepatic dysfunction.
      Light-exposed parenteral solutions containing amino acids, in addition to
      vitamins and trace minerals, generate free radicals, which, in turn, may
      contribute to this type of injury. This study examined the characteristics of
      H2O2 production in a parenteral amino acid solution modelled on a commercially
      available paediatric parenteral amino acid solution. 2. The solution was exposed
      to light in the presence of riboflavin-5'-monophosphate (riboflavin), and
      peroxide formation in the presence and absence of catalase (H2O2 formation) was
      assayed using potassium iodide/molybdate. 3. Peak H2O2 production occurred at a
      light intensity of 8 microW cm-2 nm-1 in the 425-475 nm waveband and was linear
      to 2 h of light exposure. H2O2 production reached 500 mumol/l at 24 h. 4. H2O2
      was directly related to a riboflavin concentration of up to 20 mumol/l and was
      maximal at 30 mumol/l. 5. H2O2 production was greatest in the amino
      acid/riboflavin solution at a pH of between 5 and 6. 6. Under the conditions of
      light exposure intensity, light exposure time, riboflavin concentration and pH
      found during the administration of parenteral nutrition in neonatal intensive
      care units, net H2O2 production occurs in solutions modelled on a paediatric
      parenteral amino acid preparation.

PMID- 8287664
TI  - Renal uric acid handling in non-insulin-dependent diabetic patients with elevated
      glomerular filtration rates.
AB  - 1. Hypouricaemia is prevalent in diabetic patients. In most of the studies, the
      diabetic patients had some degree of diabetic nephropathy as evidenced by a
      decreased glomerular filtration rate and proteinuria. Therefore we studied renal
      uric acid handling in a group of type II diabetic patients with elevated
      glomerular filtration rates. 2. Eighteen type II diabetic patients with normal
      kidney functions and elevated glomerular filtration rate and a group of 18
      healthy, age- and weight-matched control subjects, were studied. Serum
      fructosamine, creatinine and uric acid levels were determined. Twenty-four hour
      urine collections were obtained, and microalbumin, glucose, creatinine and uric
      acid, were measured. 3. The creatinine clearance was higher and the serum uric
      acid concentration was lower in the diabetic patients (P < 0.05). The 24 h
      urinary uric acid excretion and filtered uric acid load were similar in both
      groups. However, the derived parameters of uric acid clearance and fractional
      excretion were significantly higher in the diabetic patients (P < 0.002 and P <
      0.05, respectively). A negative correlation was apparent between serum
      fructosamine concentration and serum uric acid concentration (r = -0.76). A
      positive correlation was found between serum fructosamine concentration and
      fractional uric acid excretion (r = 0.64) and between serum fructosamine
      concentration and filtered uric acid load (r = 0.66). A positive correlation was
      found between creatinine clearance and 24 h uric acid excretion (r = 0.61) and
      between creatinine clearance and filtered uric acid load (r = 0.82).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8287665
TI  - Role of haematocrit in mediating the actions of chronic erythropoietin treatment
      on blood pressure and renal haemodynamics in the rat.
AB  - 1. This investigation aimed to study the effect of chronic administration of
      human recombinant erythropoietin on haematocrit, blood pressure, renal cortical
      and papillary resistances and vascular responsiveness to vasoconstrictor agents.
      2. Rats were treated with placebo or 25, 50 or 100 units/kg erythropoietin
      subcutaneously, every other day for 3 weeks. Animals were then anaesthetized with
      sodium pentobarbitone and were prepared for laser-Doppler flowmetry measurement
      in the renal cortex and papilla. 3. Haematocrit in the placebo-treated group was
      48.0 +/- 0.5% and was raised to 52.5 +/- 0.7, 55.9 +/- 0.8 and 62.4 +/- 1.1% (all
      P < 0.05) by the chronic administration of 25, 50 and 100 units/kg doses of the
      hormone, respectively. Blood pressure was 107 +/- 1 mmHg in the placebo-treated
      group and was elevated to 116 +/- 2 and 130 +/- 1 mmHg (both P < 0.05),
      respectively, by the two highest doses of erythropoietin. Cortical and papillary
      perfusions were reduced at the highest dose of erythropoietin, but calculated
      resistances were increased by 15 and 40% (P < 0.05) at 50 and 100 units/kg doses
      of the hormone, respectively. 4. Infusion of the vasopressor hormones vasopressin
      and phenylephrine caused increases in blood pressure and decreases in renal
      cortical and papillary perfusion, the magnitudes of which were only marginally
      changed by the highest dose of the erythropoietin. Angiotensin II increased blood
      pressure and decreased cortical perfusion, and the magnitudes of these responses
      were unchanged by the chronic treatment with erythropoietin. 5. Acute graded
      increases in haematocrit resulted in significantly (P < 0.05) raised blood
      pressure above a value of 58%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287666
TI  - Effects of haemodialysis and continuous ambulatory peritoneal dialysis on
      abnormalities of ion transport in vivo in patients with chronic renal failure.
AB  - 1. We have studied Na+/K+ pump activity in vivo in three groups of subjects:
      patients with chronic renal failure not receiving maintenance dialysis, patients
      being treated by either haemodialysis or continuous ambulatory peritoneal
      dialysis, and matched control subjects. 2. To do this we have measured the
      changes in plasma and intraerythrocytic rubidium concentrations after an oral
      load of rubidium chloride, having previously shown that changes in the
      disposition of rubidium measured in this way reflect changes in the activity of
      the Na+/K+ pump in vivo. 3. Erythrocyte rubidium uptake was significantly reduced
      both in ten patients with chronic renal failure not receiving maintenance
      dialysis and in 12 patients being treated by haemodialysis, when compared with 31
      healthy control subjects. In contrast, erythrocyte rubidium uptake was not
      altered in 13 patients treated by continuous ambulatory peritoneal dialysis.
      There was also a significantly reduced rate constant for erythrocyte rubidium
      uptake in patients with undialysed chronic renal failure (0.66 h-1) and in those
      treated by haemodialysis (0.78 h-1), whereas in patients treated by continuous
      ambulatory peritoneal dialysis the rate constant for erythrocyte rubidium uptake
      was not significantly different from control values (1.36 h-1 and 1.41 h-1,
      respectively). 4. These findings are consistent with a reversal of the inhibition
      of erythrocyte Na+/K+ pump activity in vivo found in chronic renal failure by
      continuous ambulatory peritoneal dialysis, but not by haemodialysis. This
      difference may be due to the failure of haemodialysis to clear a circulating
      inhibitor of Na+, K(+)-ATPase or to the rapid re-accumulation of such an
      inhibitor after haemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287668
TI  - Interactions of hydrogen peroxide with interleukin-6 and platelet-derived growth
      factor in determining mesangial cell growth: effect of repeated oxidant stress.
AB  - 1. This study examined the influence of H2O2, interleukin-6 and platelet-derived
      growth factor on the proliferation of rat mesangial cells. Mesangial cells were
      exposed to either a single pulse or three daily pulses of H2O2 (10(-8)-10(-4)
      mol/l), alone or in combination with interleukin-6 (5 ng/ml) and/or platelet
      derived growth factor (10 ng/ml). Proliferation was assessed after 24 h and 72 h
      of incubation using [3H]thymidine incorporation and cell counts. 2. Although one
      pulse of H2O2 had no significant effect on mesangial cell proliferation, three
      daily pulses of 10(-6) mol/l H2O2 resulted in a significant increase in
      [3H]thymidine incorporation of 31 (52.6, 10.3)% (median and 75th-25th
      interquartile range) (P < 0.001). Both interleukin-6 and platelet-derived growth
      factor were also mitogenic to mesangial cells, [3H]thymidine incorporation
      increasing by 19 (36.7, -6.7)% (P < 0.05) and 53.5 (107, 21.9)% (P < 0.001),
      respectively. The mitogenic effect of interleukin-6 was enhanced by 10(-6) mol/l
      H2O2 [49.9 (77.7, 12.3)%] (P < 0.01), whereas the addition of 10(-6) mol/l H2O2
      to platelet-derived growth factor resulted in a summated increase in
      [3H]thymidine incorporation of 82.7 (113, 57.4)% (P < 0.001). Incubation with all
      three substances simultaneously resulted in down-regulation of growth compared
      with H2O2 plus platelet-derived growth factor by 55.4 (77.7, 10.3)% (P < 0.05).
      3. These findings suggest that reactive oxygen species may play a major role in
      determining the mesangial cell proliferation that occurs in certain forms of
      glomerulonephritis, acting either alone or in combination with other growth
      factors.

PMID- 8287667
TI  - Change in macromolecular composition of interstitial fluid from swollen arms
      after breast cancer treatment, and its implications.
AB  - 1. The pathophysiology of chronic arm oedema after treatment of breast cancer was
      investigated by collecting serum and subcutaneous interstitial fluid from the
      affected and contralateral arms by the wick method (both arms) and by aspiration
      (oedematous arm). The fluids were analysed for total protein, albumin,
      glycosaminoglycan and viscosity, and arm volume was measured. 2. Total protein
      concentration in the aspirated oedema fluid was 32.4 +/- 7.5 g/l (mean +/- SD
      throughout; n = 39). Protein concentration in wick fluid from the oedematous arm
      (35.8 +/- 7.3 g/l, n = 14) was not significantly different from that in aspirated
      fluid. The oedema protein concentrations were significantly lower than in wick
      fluid from the non-swollen arm (41.4 +/- 6.7 cmH2O, n = 13, P < 0.01, analysis of
      variance). This was surprising in view of the common assumption that, the
      condition being of lymphatic origin, the oedema protein concentration should be
      raised. 3. The ratio of aspirate protein concentration to serum protein
      concentration showed a weak but highly significant negative correlation with the
      percentage increase in arm volume (r = -0.47, n = 35, P < 0.005), again in
      contrast to conventional expectation. The demonstration of a reduced protein
      concentration in the swollen arm did not therefore depend solely on a comparison
      with the wick control results. The volume increased by on average 33% and the
      ratio of aspirate protein concentration to serum protein concentration averaged
      0.52 +/- 0.11 on the swollen side and 0.64 +/- 0.13 on the unaffected side. 4.
      Serum protein concentration in the patients with arm swelling (61.2 +/- 4.9 g/l)
      was significantly lower than that in postmastectomy patients without this
      complication (65.0 +/- 6.2 g/l). Most of the decrease occurred in the albumin
      fraction (oedema patients, 38.3 +/- 5.1 g/l; control patients, 42.0 +/- 2.1 g/l).
      In oedema patients receiving the anti-oestrogen tamoxifen serum albumin
      concentration was on average 2.3 g/l lower than in oedema patients not under
      medication (P < 0.05, t-test). 5. Glycosaminoglycan concentration in oedema fluid
      was 0.8 +/- 0.14 g/l (n = 21) and 75% was sulphated. Along with the plasma
      protein this raised the relative viscosity of the fluid to 1.34 +/- 0.16 (n =
      11). 6. The reduction in interstitial protein concentration in the swollen arm,
      contrary to expectation in lymphoedema, could be explained in several ways. One
      possible hypothesis in light of reported haemodynamic abnormalities in such arms
      is that capillary pressure rises, increasing capillary filtration rate.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8287669
TI  - Viral infection of bovine bronchial epithelial cells induces increased neutrophil
      chemotactic activity and neutrophil adhesion.
AB  - 1. Acute bronchitis secondary to viral infection is associated with an influx of
      neutrophils. We hypothesized that bronchial epithelial cells are capable of
      releasing neutrophil chemotactic activity in response to viral infection. 2. To
      test this hypothesis, primary cultures of bovine bronchial epithelial cells were
      inoculated with a bovine respiratory pathogen, bovine herpes virus-1. 3.
      Supernatants collected from inoculated cells, before signs of toxicity,
      demonstrated significant neutrophil chemotactic activity using a blind well
      chamber neutrophil chemotaxis assay. Lipoxygenase inhibitors markedly reduced the
      amount of neutrophil chemotactic activity released after bovine herpes virus-1
      inoculation. Analysis of arachidonic acid metabolites in cell supernatants by
      reverse-phase h.p.l.c. confirmed that leukotriene B4, a potent neutrophil
      chemoattractant, was released. 4. We also confirmed that adhesion of neutrophils
      to bovine herpes virus-1-inoculated bronchial epithelial cells was increased and
      mediated in part by the neutrophil integrin, LFA-1. 5. Thus, virally infected
      airway epithelial cells release leucocyte chemoattractants and hence adhesive
      interactions, functions that are likely to be important in the inflammatory acute
      response to viral infection.

PMID- 8287670
TI  - The interaction between reasoning and decision making: an introduction.

PMID- 8287671
TI  - Reason-based choice.
AB  - This paper considers the role of reasons and arguments in the making of
      decisions. It is proposed that, when faced with the need to choose, decision
      makers often seek and construct reasons in order to resolve the conflict and
      justify their choice, to themselves and to others. Experiments that explore and
      manipulate the role of reasons are reviewed, and other decision studies are
      interpreted from this perspective. The role of reasons in decision making is
      considered as it relates to uncertainty, conflict, context effects, and normative
      decision rules.

PMID- 8287672
TI  - Reasoning in explanation-based decision making.
AB  - A general theory of explanation-based decision making is outlined and the
      multiple roles of inference processes in the theory are indicated. A typology of
      formal and informal inference forms, originally proposed by Collins (1978a,
      1978b), is introduced as an appropriate framework to represent inferences that
      occur in the overarching explanation-based process. Results from the analysis of
      verbal reports of decision processes are presented to demonstrate the centrality
      and systematic character of reasoning in a representative legal decision-making
      task.

PMID- 8287673
TI  - Reasoning, decision making and rationality.
AB  - It is argued that reasoning in the real world supports decision making and is
      aimed at the achievement of goals. A distinction is developed between two notions
      of rationality: rationality which is reasoning in such a way as to achieve one's
      goals--within cognitive constraints--and rationality which is reasoning by a
      process of logic. This dichotomy is related to the philosophical distinction
      between practical and theoretical reasoning. It is argued that logicality
      (rationality) does not provide a good basis for rationality and some
      psychological research on deductive reasoning is re-examined in this light.
      First, we review belief bias effects in syllogistic reasoning, and argue that the
      phenomena do not support the interpretations of irrationality that are often
      placed upon them. Second, we review and discuss recent studies of deontic
      reasoning in the Wason selection task, which demonstrate the decision making, and
      rational nature of reasoning in realistic contexts. The final section of the
      paper examines contemporary decision theory and shows how it fails, in comparable
      manner to formal logic, to provide an adequate model for assessing the
      rationality of human reasoning and decision making.

PMID- 8287674
TI  - Focussing in reasoning and decision making.
AB  - Our principal hypothesis is that reasoning and decision making are alike in that
      they both depend on the construction of mental models, and so they should both
      give rise to similar phenomena. In this paper, we consider one such phenomenon,
      which we refer to as "focussing": individuals are likely to restrict their
      thoughts to what is explicitly represented in their models. We show that
      focussing occurs in four domains. First, individuals fail to draw inferences in
      the modus tollens form: if p then q, not-q, therefore not-p, because they focus
      on their initial models of the conditional, which make explicit only the case
      where the antecedent (p) and consequent (q) occur. Second, in Wason's selection
      task, they similarly tend to select only those cards that are explicitly
      represented in their initial models of the conditional rule. Third, their
      requests for information in order to enable them to make a decision about whether
      or not to carry out a certain action are focussed on the action to the exclusion
      of alternatives to it. In each of these cases, we show how the focussing bias can
      be reduced by certain experimental manipulations. Finally, in counterfactual
      reasoning, focussing underlies individuals' attempts to imagine an alternative
      scenario that avoids an unfortunate ending to a story.

PMID- 8287675
TI  - Similarity, plausibility, and judgments of probability.
AB  - Judging the strength of an argument may underlie many reasoning and decision
      making tasks. In this article, we focus on "category-based" arguments, in which
      the premises and conclusion are of the form All members of C have property P,
      where C is a natural category. An example is "Dobermans have sesamoid bones.
      Therefore, German shepherds have sesamoid bones." The strength of such an
      argument is reflected in the judged probability that the conclusion is true given
      that the premises are true. The processes that mediate such probability judgments
      depend on whether the predicate is "blank"--an unfamiliar property that does not
      enter the reasoning process (e.g., "have sesamoid bones")--or "non-blank"--a
      relatively familiar property that is easier to reason from (e.g., "can bite
      through wire"). With blank predicates, probability judgments are based on
      similarity relations between the premise and conclusion categories. With non
      blank predicates, probability judgements are based on both similarity relations
      and the plausibility of premises and conclusion.

PMID- 8287676
TI  - Debias the environment instead of the judge: an alternative approach to reducing
      error in diagnostic (and other) judgment.
AB  - Questions about how to improve human judgment and reasoning are of theoretical
      and practical interest, notwithstanding the continuing controversy over whether
      people are "rational". Improving judgment may involve modifying people's
      processes to fit their environments better, or vice versa. We illustrate the
      latter approach in a study of diagnostic reasoning in which subjects learned to
      distinguish two fictitious diseases. Prior findings suggest that people may judge
      the likelihood of a diagnostic category on the presence or absence of features
      that are typical of, rather than diagnostic of, the category. We varied the
      structure of the information provided to subjects without attempting to modify
      their judgmental processes. In an "independent" format, subjects learned about
      each disease separately; in a "contrastive" format, information about the two
      diseases was juxtaposed to highlight distinctive features. Subjects in the two
      conditions formed different disease concepts. Diagnoses following contrastive
      training were much closer to the statistically prescribed judgments based on
      likelihood ratios. Interventions that modify the environment may provide an
      alternative approach where it is difficult to modify people's processes.
      Effective design of such interventions is one motivation for directing research
      toward understanding how task characteristics affect the use of and the outcomes
      of judgment and reasoning processes.

PMID- 8287677
TI  - Meconium staining of the amniotic fluid: the need for reassessment of management
      by obstetricians and pediatricians.

PMID- 8287678
TI  - Diagnosis and treatment for children who cannot control urination.
AB  - Primary NE is probably a condition rooted in biologic problems. There is a strong
      hereditary component. Altered nervous system function may lead to disorganization
      of how bladder function is controlled and how vasopressin is released. In extreme
      cases, this disorganization may also be reflected in psychologic issues, such as
      attention-deficit disorder. Primary NE should not be viewed as laziness of the
      child, but as an obstacle the child needs professional help to hurdle. The
      practitioner should collaborate with a pediatrician, urologist, and psychologist
      in managing children who wet. Routine office evaluation should exclude
      incontinence as a cause of wetting. When a screening ultrasonogram is normal,
      this helps the practitioner determine that striking birth defects are unlikely.
      Follow-up of management by interview with interested staff is necessary. Wetting
      is reliably correctable and probably best addressed by combination treatment
      structured as an ETP. Specific treatments vary according to personal preferences.
      The treatment with strongest scientific research, desmopressin, may be the least
      effective for cure. The most effective treatment for cure, alarm with behavior
      reinforcement, is the least often prescribed. A miscellany of adjunctive
      treatments should be suggested when there are abnormalities in functional bladder
      capacity, defecation, urethritis, vulvitis, diet sensitivity, upper-airway
      obstruction, and other areas.

PMID- 8287679
TI  - The gene encoding myeloid alpha-3-fucosyl-transferase (FUT4) is located between
      D1 1S388 and D11S919 on 11q21.
AB  - The last step in the biosynthesis of Le(x) antigen, the addition of a fucose to
      precursor polysaccharides, can be catalyzed by different alpha-3
      fucosyltransferases. We localized the gene (FUT4) encoding myeloid alpha-3
      fucosyltransferase by PCR assay using panels of somatic cell and radiation
      hybrids which retain different rearrangements of chromosome 11. FUT4 was assigned
      to chromosome band 11q21 between D11S388 and D11S919.

PMID- 8287680
TI  - In situ hybridization approach at infragenic level on metaphase chromosomes.
AB  - Analysis of the retinoblastoma locus (RB1) by in situ hybridization at the
      infragenic level was done using human chromosomes. A high level of resolution was
      attained with nonisotopic in situ hybridization on banded chromosomes in both
      fluorescence and electron microscopy. DNA sequences less than 100 kb apart could
      be positioned on band 13q14 in the order expected from molecular mapping. These
      observations suggest that the DNA target of hybridized probes on metaphase
      chromosomes may correspond to nucleoprotein loops giving a resolution comparable
      to that obtained in interphase nuclei.

PMID- 8287681
TI  - Localization of the CAMKG gene encoding gamma isoforms of multifunctional
      calcium/calmodulin-dependent protein kinase (CaM kinase) to human chromosome 10
      band q22 and mouse chromosome 14.
AB  - Multifunctional calcium/calmodulin-dependent protein kinase (CaM kinase) is an
      enzyme mediating calcium-dependent signal transduction pathways. CaM kinase
      exists in a variety of isoforms, each with a distinct tissue-specific expression
      pattern, that enables the kinase to regulate multiple functions in mammalian
      systems. Here we report the chromosomal localization of the previously cloned
      human gamma-CaM kinase gene (CAMKG). By using a mapping panel of human x Chinese
      hamster somatic cell hybrid lines and fluorescence in situ hybridization, we have
      assigned human CAMKG to chromosome 10q22. We have partially cloned the murine
      gamma-CaM kinase gene and mapped it Camkg to mouse chromosome 14 by analyzing a
      panel of mouse x rodent somatic cell hybrid lines. A recessive gene, asa,
      implicated in the control of autoimmune response, is located within the predicted
      region for Camkg.

PMID- 8287682
TI  - Assignment of the gene encoding the latent TGF-beta 1-binding protein (LTBP1) to
      human chromosome 2, region p12-->q22.
AB  - Latent transforming growth factor beta 1-binding protein (LTBP1) is an important
      component of the large latent TGF-beta 1 complex. It plays a role in the assembly
      and secretion of the latent TGF-beta 1. In this paper we have used a cDNA probe
      for LTBP1 to determine the chromosomal localization of the human gene. Using a
      panel of well-defined human x rodent somatic cell hybrid lines, LTBP1 could be
      assigned to chromosome 2. Further sublocalization of the gene to 2p12-->q22 was
      achieved using three hybrid lines which contain partially over-lapping fragments
      of chromosome 2.

PMID- 8287683
TI  - Chromosomes are highly elastic and can be stretched.
AB  - Direct manipulation of human chromosomes in metaphase spreads using glass needles
      revealed that the consistency of chromosomes varies depending on their moisture
      content. Chromosomes are soft and highly elastic under wet conditions and are
      hard when dry. The elasticity of chromosomes is comparable to rubber threads and
      can be used for stretching experiments under phase contrast microscopy, after
      Giemsa staining, and after GTG-banding. The coiling structures of the chromosomes
      appear to be stretched evenly along the length of the chromosome. Chromosomes
      fixed for only a short time have a tendency to tear when stretched more than 5
      times their length. Under the experimental conditions used, chromosomes were
      preferentially torn in the centromeric region. Chromosome stretching on GTG
      banded human chromosomes leads to a splitting of bands into their subbands. This
      may be useful for creating new high resolution ideograms possibly showing more
      than 1700 bands per haploid set.

PMID- 8287684
TI  - Cell-cycle-stage specificity of the methotrexate block as resolved by X-ray
      induced chromosome damage.
AB  - Radiation-induced chromosome aberrations were used as biomarkers to compare G0,
      mid-G1, and methotrexate (MTX)-arrested lymphocytes. The ratio of chromosome-type
      to chromatid-type aberrations in MTX-arrested cells was consistent with that
      predicted when postreplicative chromosomes are exposed to ionizing radiation and
      supports the premise that MTX arrests cells in late S/G2 of the cell cycle.

PMID- 8287685
TI  - Assignment of the human gene encoding the epidermal serine proteinase inhibitor
      SKALP (PI3) to chromosome region 20q12-->q13.
AB  - Recently we isolated a cDNA clone corresponding to an epidermal serine proteinase
      inhibitor named SKALP (skin-derived antileukoproteinase). Here we report the
      chromosomal localization of the human gene encoding SKALP by Southern blot
      analysis of a panel of human x hamster hybrid cell lines and by nonradioactive in
      situ hybridization on R-banded human lymphocyte chromosome spreads. The SKALP
      encoding gene has been assigned the approved symbol PI3 by the Human Gene Mapping
      nomenclature committee.

PMID- 8287686
TI  - Assignment of the human PAX4 gene to chromosome band 7q32 by fluorescence in situ
      hybridization.
AB  - Of the nine known members of a human paired box-containing gene family (Pax),
      only PAX4 has not been precisely localized. We screened a cosmid library of human
      genomic DNA using polymerase chain reaction products for PAX4 as a probe and
      isolated three positive cosmid clones. Sequence analysis revealed that at least
      two of them had exon-like sequences and showed extensive homology to Pax-4 in the
      mouse. These two cosmid clones were mapped to human chromosome band 7q32 by
      fluorescence in situ hybridization.

PMID- 8287687
TI  - Cytogenetic analysis of malformed mouse fetuses derived from balanced
      translocation heterozygotes.
AB  - Reciprocal translocations are readily induced by various physical and chemical
      mutagens in certain germ-cell stages. Carriers of balanced reciprocal
      translocations generally exhibit no abnormal phenotypes, except for occasional
      male sterility, but about half (on average) of their progeny carry grossly
      unbalanced chromosome complements and die prenatally, so that the carriers are
      said to be 'semisterile'. Since death of such progeny generally occurs in very
      early embryonic stages, it would be of minor importance in an analogous human
      situation. Several types of unbalanced segregants, however, survive to late
      gestational or even to postnatal stages and are often malformed. Recently, it was
      determined in this laboratory that over one half of the male carriers of
      methylene-bisacrylamide-induced translocations, sired litters that had late-dying
      and/or malformed fetuses (Rutledge et al., 1990). Five high-anomaly translocation
      stocks derived from that study and four derived from studies with other mutagens
      were analyzed cytogenetically to determine (1) the chromosomes and breakpoints
      involved, (2) the nature of chromosome imbalance in malformed fetuses, and (3)
      the types of meiotic segregation that produce late-surviving unbalanced
      segregants. Cytogenetic analysis of the 9 translocation stocks revealed 18
      breakpoints located in 12 chromosomes. Each translocation had at least one
      breakpoint located near the centromere or the telomere. All translocations
      produced abnormal fetuses that were partially monosomic for a very short terminal
      chromosome segment, and partially trisomic for a segment that can be of various
      lengths, 2-10 times as long as the monosomic segment. In 6 stocks, these abnormal
      fetuses arose by adjacent-1 or alternate segregation; in the other three they
      arose by adjacent-2 segregation. In addition, tertiary trisomy by 3-1
      missegregation was also observed in two of the stocks.

PMID- 8287688
TI  - Genetic control of sex-chromosome inactivation during male meiosis.
AB  - During meiotic prophase in male mammals, the sex chromosomes are
      transcriptionally inactivated and form a condensed chromatin domain known as the
      sex body. It is not known how the assumption of this chromatin configuration is
      determined and regulated. We used various genetic models to test whether a
      complete sex-chromosome pair, effective sex-chromosome pairing, or an intact X
      chromosome is required for sex-body formation or transcription inactivation. The
      sex chromosome aberrations studied did not interfere with sex-body formation, and
      there is no evidence for inactivation failure or reactivation of the aberrant sex
      chromosomes. The results of this study suggest that control of sex-body formation
      is not intrinsic to the sex chromosomes and thus may be at the level of the
      testis.

PMID- 8287689
TI  - The chromosomal distribution of Mus musculus-like AT-rich heterochromatin in the
      M. dunni complex as revealed by AluI digestion of metaphase chromosomes.
AB  - In situ digestion of metaphase chromosomes with AluI revealed differences in the
      distribution of Mus musculus-like AT-rich heterochromatin in the complements of
      the Indian pygmy field mice, M. booduga and M. dunni. In M. booduga, although the
      banding pattern was almost comparable to that of M. musculus, AluI-resistant
      bands were much reduced in size at the centromeric regions. In all three
      chromosome types of the M. dunni complex, M. musculus-like AT-rich
      heterochromatin was found to be confined mainly to two small segments on the
      short arm of the X chromosome. This AT-rich heterochromatin varied greatly in
      both position and quantity in the two X chromosomes. In addition to the
      polymorphism, a whole block of M. musculus-like AT-rich heterochromatin was found
      at the centromeric region of an autosome in one individual of M. dunni.

PMID- 8287690
TI  - Regional assignment of the human immunoglobulin processed pseudogene C epsilon 3
      (IGHEP2) to 9p24.2-->p24.1 by fluorescence in situ hybridization.
AB  - The human immunoglobulin processed pseudogene C epsilon 3 (IGHEP2), which was
      assigned to chromosome 9 by somatic cell hybrid analysis, has not been regionally
      localized as yet. In this study, using fluorescence in situ hybridization (FISH)
      combined with conventional QFQ-, RBG- or GTG-banding, IGHEP2 was assigned to the
      p terminus region of chromosome 9, at band 9p24.2-->p24.1. This result suggests
      that the C epsilon 3 gene is a novel telomeric DNA marker useful not only for
      constructing the physical map of human chromosome 9 but also for cytogenetic
      analyses such as cryptic translocations. In addition, comparative mapping of this
      gene in other catarrhine primates would contribute to investigations of human and
      other primate karyotype evolution.

PMID- 8287691
TI  - The human glutathione peroxidase genes GPX2, GPX3, and GPX4 map to chromosomes
      14, 5, and 19, respectively.
AB  - cDNA probes of human glutathione peroxidase (GSHPx) genes, including the classic
      GPX1 (GSHPx-1), the newly characterized GPX2 (GSHPx-GI), the plasma enzyme GPX3
      (GSHPx-P), and the phospholipid hydroperoxide glutathione peroxidase GPX4
      (PHGPX), were hybridized to Southern blots containing genomic DNA from human x
      hamster somatic cell hybrids. GPX2 was mapped to chromosome 14, GPX3 to
      chromosome 5 and GPX4 to chromosome 19. Additionally, human chromosomes 3 and 21
      and the X chromosome were shown to contain sequences homologous to GPX1, as
      reported previously.

PMID- 8287692
TI  - A mammalian homologue of Drosophila heterochromatin protein 1 (HP1) is a
      component of constitutive heterochromatin.
AB  - The Drosophila HP1 gene contains a highly conserved sequence, the chromobox,
      which can be used to isolate HP1-like genes from both mouse (M31 and M32) and man
      (HSM1) (Singh et al., 1991). Here we report that a monoclonal antibody (MoAb)
      raised against the M31 protein recognises a 26-kDa protein in murine and human
      nuclear extracts and localises to large masses of condensed chromatin within
      murine interphase nuclei, some of which are associated with the nucleoli. At
      metaphase, the MoAb binds to the centromeres of both human and murine
      chromosomes. The evolutionary conservation of this chromosomal localisation
      indicates that the M31 protein is likely to be important in the packaging of
      mammalian chromosomal DNA into constitutive heterochromatin.

PMID- 8287693
TI  - Post-traumatic stress disorder in children and adolescents of the Armenian
      earthquake.
AB  - The impact of the Armenian earthquake of 1988 on children and adolescents
      screened through the National Mental Health Research Center in Spitak, Armenia,
      is discussed. The earthquake caused close to 20,000 deaths, almost two-thirds of
      which were children and adolescents. Clinical data which address advances in
      understanding the diagnostic indicators and resulting psychopathology in victims
      of the Armenian earthquake are presented. Current theory about the processing of
      trauma in children and adolescents is reviewed, with recommendations for future
      research in this area.

PMID- 8287694
TI  - Parental overprotection revisited.
AB  - Dimensions of parental overprotection are clarified in a critical review of the
      research and clinical literature. An indulgent style of parenting is
      distinguished from an overprotective parent-child relationship. Differential
      antecedents and outcomes are proposed for each of these forms of parent-child
      interaction. Measures of protection are reviewed. A new conceptual model of
      parental overprotection is presented which takes into account child, parent,
      family, socio-cultural, environmental and resiliency factors. Directions for
      future research are suggested.

PMID- 8287695
TI  - Adolescent pregnancy: an intervention challenge.
AB  - Even in the best of circumstances, pregnancy is a time of emotional upheaval.
      This is especially true for pregnant adolescents who are also attempting to
      adjust to pubertal status and to establish an identity independent from their
      family. Although research has focused on the etiology of teenage pregnancy,
      relatively few interventions consider the developmental obstacles encountered
      when treating pregnant teenagers. In particular, adolescents are cognitively
      unprepared to predict long-term outcomes, a skill essential for confronting the
      challenges of pregnancy. One new intervention, known as previewing, seeks to
      overcome this deficit. Previewing encourages expectant teenage mothers to
      represent future scenarios with the infant as a means of predicting and
      rehearsing adaptive outcomes.

PMID- 8287696
TI  - Plasma endothelin levels in cirrhotic patients and their correlation with atrial
      natriuretic peptide.
AB  - Plasma levels of endothelin (ET) were determined by radioimmunoassay in 11
      healthy volunteers and 34 patients with liver cirrhosis. The results revealed
      that mean ET plasma level was significantly lower in 34 cirrhotic patients than
      in normal subjects (40.21 +/- 4.38 ng/L vs 84.55 +/- 7.88 ng/L, P < 0.01). Plasma
      ET was 32.17 +/- 3.98 ng/L in 23 cirrhosis patients with ascites compared with
      57.0 +/- 9.0 ng/L in patients without ascites (P < 0.01). Moreover, it is
      apparent that plasma levels of ET decreased with the increase of ascites volume,
      and increased after the disappearance of ascites. But plasma levels of atrial
      natriuretic peptide (ANP) in cirrhotic patients were markedly higher than those
      in the controls (830.12 +/- 72.18 ng/L vs 439.45 +/- 50.18 ng/L, P < 0.01). In
      patients with ascites, ET plasma levels were inversely correlated to ANP. The
      results suggest that deficiency of circulating ET might be one of the important
      factors involved in sodium and water retention in cirrhosis.

PMID- 8287697
TI  - Alterations of serum phospholipids in patients with multiple sclerosis.
AB  - The total phospholipids in serum and the percentages of major phospholipid
      classes of phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylethanol
      amine (PE) and sphingomyelin (SM) were studied based on 21 patients with multiple
      sclerosis (MS) and 18 healthy subjects. Serum samples were extracted with
      isopropanol, then major phospholipid classes were separated by thin-layer
      chromatography, finally, the samples were quantitated by CS-910 densitometer.
      Though the results were insignificantly different in the concentration of total
      phospholipid between the MS patients and the controls, there was partial
      reduction of the concentrations of PS and PE (P < 0.01), moreover, the
      percentages of PS and PE were relatively lower, correspondingly, the percentage
      of PC was higher as compared with control group. The results suggest that there
      should exist an abnormality in the metabolism of phospholipids in patients with
      MS in the sense of the alterations of phospholipid compositions in serum samples.

PMID- 8287698
TI  - Radiofrequency current ablation of atrioventricular accessory pathway.
AB  - Catheter ablation of atrioventricular accessory pathway by radiofrequency current
      is a new treatment for patients with refractory supraventricular tachycardia. 71
      patients (37 male, 34 female, mean age 36 +/- 11 years) with 77 atrioventricular
      accessory pathways were ablated in the study. Left-sided pathways were ablated at
      the ventricular side of mitral annulus by using large-tip ablation catheter.
      While right-sided pathways were ablated along the tricuspid annulus, 70 (90.9%)
      accessory pathways of 64 patients (90.1%) were blocked successfully. There were
      no deaths. Left femoral vein thrombosis occurred in one patient. Recurrence was
      found in 3 patients (4.2%) after 7 months of follow-up and all of them were
      ablated again successfully.

PMID- 8287699
TI  - Immunological status and pathology of coxsackie B viral myocarditis and dilated
      cardiomyopathy.
AB  - The changes in 15 cases of viral myocarditis and 28 cases of dilated
      cardiomyopathy were reported and compared, which were the pathological changes of
      endomyocardial biopsy; NK cells activity; % of peripheral T lymphocytes and its
      subsets determined by using OKT3,4,8 (OKT3-peripheral total lymphocytes; OKT4
      helper cells; OKT8-suppressive cells) monoclonal antibody; values of
      immunoglobulin IgG, IgA, IgM; titer of coxsackie B antibody neutralization test.
      And a discussion on their relationship was included.

PMID- 8287700
TI  - Experimental studies of laser myocardial revascularization in rats.
AB  - Myocardial revascularization by Nd: YAG laser used in rats with myocardial
      infarction was studied. The left coronary artery was ligated and the laser
      channels with a diameter of 300 microns were made immediately by 2.5-4.2 W
      lasersonics YAG unit. After 24 hours, the rats were killed. Evaluation included
      hemodynamics, lactate dehydrogenase of myocardium and myocardial infarct size.
      The results showed that laser myocardial revascularization reduced myocardial
      infarct size and enzyme leakage, and improved left ventricular function. The
      study may provide theoretical basis for the clinical applications of this new
      technique in the treatment of ischemic heart disease.

PMID- 8287701
TI  - Endoscopic variceal ligation. Experience in 78 patients.
AB  - Endoscopic variceal ligation (EVL) is a new alternative to sclerotherapy in the
      treatment of esophageal variceal hemorrhage, which results in strangulation,
      necrosis and scar formation of varices without systemic or local adverse effect.
      From May 1, 1991 through July 1, 1992, EVL was performed in 78 consecutive
      patients, in 35 of them it was performed during active massive bleeding, and
      active bleeding was controlled by the initial session in 31 patients. With
      repeated EVL treatment, 32 patients had their varices obliterated. The varices
      had reduced in size in other patients. No ligation-related complications were
      observed. This procedure is a safe, effective and rather simple method to treat
      esophageal varices, especially in patients with poor liver function and recurrent
      bleeding after devascularization or shunt surgery.

PMID- 8287702
TI  - Hyperselective posterior rhizotomy in treatment of spasticity of paralytic limbs.
AB  - One hundred and eight patients with spasticity of the paralytic limbs were
      treated successfully with hyperselective posterior rhizotomy (SPR). Of the 108
      patients, 100 had cerebral palsy, 2 hemiplegia, 3 sequelae of cerebral injury, 2
      paraplegia and 1 multiple sclerosis. Twelve patients received cervical SPR and 96
      lumbosacral SPR. Laminectomy is performed to open the dura and to separate the
      posterior spinal root into several rootlets. The lower threshold rootlets were
      divided after electrical stimulation. Follow-up for 6 to 30 months showed that
      the effective rate of reducing spasticity was over 95% and functional improvement
      rate over 80%.

PMID- 8287703
TI  - Monitoring and control of infection in patients after renal transplantation.
AB  - Infection is a leading cause of death of renal transplantation and how to control
      it is still an urgent problem to be solved. Bacteria culture, computerized
      modified McGuckin's monitoring methods, OKT monoclonal antibody technique and
      radioimmunoassay (RIA) were used on studying the cause, monitoring and prevention
      of the infection. Results showed that 22 out of 24 cases (91.7%) were colonized
      by Gram-negative bacilli in pharynx and groin region. Of them, 15 were infected
      with the same bacteria in wound, urine, blood and lung. Six out of 7 cases with
      serious infection were colonized by Gram-negative bacilli on the surface of the
      whole body. The computerized modified McGuckin's method predicted and analyzed
      the infection outbreak much more fast and accurate, with a rate of over 80%.
      Helper/suppressor lymphocyte ratio of 1.08 was taken as a threshold value for the
      diagnosis of infection. The results suggested that the change of skin flora is
      closely related with the infection. Monitoring the alteration of skin flora is an
      effective method for the prevention and control of severe infection. The pharynx
      and groin regions of the patients are stable reservoirs of Gram-negative bacilli
      which may cause infection easily. Computerized quantitative analysis may increase
      the efficiency and accuracy of infection surveillance. In order to preserve the
      immune system as much as possible and prevent rejection of transplant graft,
      proper use of immunosuppressive drugs and regulation of the immune system of the
      patients are the key for preventing infection.

PMID- 8287704
TI  - Computerized image analysis of smooth muscle fibers in normal Chinese men and
      impotence patients.
AB  - Smooth muscle fibers are considered very important in penile erection and
      relaxation. The reduction of intracavernosus smooth muscle fibers can provoke
      impotence. The percentage of smooth muscle fibers in corpus cavernosum specimens
      was studied quantitatively in normal men and impotence patients by means of
      computerized image analysis. The percentage of smooth muscle fibers in the
      specimens of 14 normal men, ranged from 41% to 61% (average 50%) and in 12
      impotence patients, it was 22% to 46% (average 31%). A decrease of smooth muscle
      fibers and an increase of collagen fibers were noted in impotence patients.

PMID- 8287705
TI  - Circulatory crisis caused by cigarette smoking in tissue transfer. Clinical and
      experimental studies.
AB  - Cigarette smoking-induced circulatory crisis occurred in two patients receiving
      toe transfer and one patient having musculocutaneous flap. After anticoagulation
      and antispasm treatment, one survived and two failed. Experimental studies
      demonstrated that cigarette smoking is harmful to the healing of endothelia at
      the anastomotic site of vessels. Five days after operation, the complete recovery
      rate of the endothelium over sutures of anastomotic sites was 16%-19% in smoking
      groups, but 75% in the control group. The mechanism and characteristics of
      circulatory crisis caused by cigarette smoking are discussed.

PMID- 8287706
TI  - Immunologic abnormalities in children with acute Kawasaki disease.
AB  - Spontaneous release of IgG, production of IgG, IgM and IgG subclasses induced by
      PWM in vitro, serum IgG, IgM, IgA and IgG subclasses were measured in 23 patients
      with acute Kawasaki disease (KD). The results showed that there was polyclonal B
      cell activation with significantly increased IgG1 and IgG3. As compared with 21
      healthy controls, the mean activities of B cell growth factors (BCGFs), B cell
      differentiation factors (BCDFs) and interleukin 6 (IL-6) were significantly
      elevated. IL-6 activity was correlated with the production of IgG, IgG1, IgG3 and
      IgM, while BCGFs and BCDFs were also correlated with IgG1. The serum level of
      circulating tumor necrosis factor (TNF) determined in 16 patients with acute KD
      using double antibody ELISA was 1.86-8.83 micrograms/ml, but it was less than 1
      microgram/L in normal controls. The clinical value of increased TNF in serum is
      discussed.

PMID- 8287707
TI  - Pathologic changes of mammillary body in clinical and experimental brain
      hemorrhage.
AB  - The histomorphologic changes of the mammillary bodies (MB) in 31 patients and 8
      spontaneously hypertensive rats with brain hemorrhage were studied by light and
      electron microscopy. The results showed that the frequency of the ischemic change
      neurons in medial nucleus in MB is much higher than that in hippocampal CA1
      section and multiplicated double-deck or multistratum basal lamina formed a
      network or branch pattern, which indicate that MB may be of important function.

PMID- 8287708
TI  - Distribution and histochemical characteristics of mast cells in stroma of the
      cervix squamous cell carcinoma.
AB  - The distribution and histochemical characteristics of mast cells in the stroma of
      cervical squamous cell carcinoma were investigated using different staining
      methods of alcian blue-safranin, berberine sulphate and toluidine blue. The
      findings suggest that mast cells in the stroma of the squamous cell carcinoma of
      the cervix might contain a glycosaminoglycan different from that of typical
      connective tissue mast cell (CTMC) and mucosal mast cell (MCC). They thus, might
      be a specific subset of mast cells though sharing some of the staining properties
      of both CTMC and MMC. In the cervical carcinoma in situ, mast cells were
      distributed closely around the tumor or the involved glands with great density
      and the number was significantly higher than that of the invasive carcinoma (P <
      0.01). In invasive carcinoma, mast cells were mainly distributed in the deep
      stroma and the stroma around the tumor, only a few in the stroma within the tumor
      (P < 0.01). The significance of mast cell reaction in the stroma of squamous cell
      carcinoma of the cervix is discussed.

PMID- 8287709
TI  - Study on neutrophil enzymes in atopic disease.
AB  - Neutrophils (PMN) from 20 patients with atopic disease (atopy), the parents of 8
      of the patients and 10 normal controls were studied by light-microscopic
      cytochemistry. The results revealed that myeloperoxidase (MPO) and acid
      phosphatase (ACP) activities in PMN in all cases significantly decreased and
      alkaline phosphatase activity was normal. Parents or parent of 7 of those
      patients had PMN enzyme deficiency similar to that of the patients. The results
      indicated that a primary combined and partial deficiency of MPO and ACP in PMN
      azurophilic granule existed in atopy. It is postulated that the deficiency led to
      reduction of PMN bactericidal power and delay of bactericidal action. Foreign
      bodies which were partially degraded could possess antigenic property. This is
      believed to be the important cytobiological mechanism of the tendency toward
      infections and formation of sensitive antigen in atopy.

PMID- 8287710
TI  - Comparison of results of laser and routine surgery therapy in treatment of nasal
      polyps.
AB  - 102 patients with nasal polyps receiving ND: YAG laser surgery or routine surgery
      were followed up for 18-36 months. The postoperative recurrence rates were 40.6%
      (24/54) and 66.6% (32/48) respectively for the patients of the two groups. Laser
      surgery is marked by less bleeding, no postoperative packing of the nose and
      lower postoperative recurrence rate, and it seems to be better than routine
      removal in the treatment of nasal polyps.

PMID- 8287711
TI  - CT scanning of spinal injuries.
AB  - Ninety-one patients with spinal injuries were studied by CT scanning. A
      comprehensive classification of spinal injuries was proposed according to the
      mechanism of trauma, the concept of three-column anatomical structure of the
      spine and the degree of spinal canal stenosis. CT scanning was advantageous in
      the diagnosis of spinal injuries such as clear detection of the three-column
      anatomical structure of the spine and spinal canal, demonstration of fracture
      lines in all 3 planes, determination of the amount of displacement of bony
      fragment into the spinal canal, assessment of spinal stability or instability,
      and restricted movement of the patient. The key points in general CT diagnosis,
      its role and limitation in the diagnosis of spinal injuries were discussed. The
      authors conclude that combined comprehensive classification of spine injuries is
      helpful in planning suitable treatment for the patient and predicting prognosis.

PMID- 8287712
TI  - A case of pseudogout.

PMID- 8287713
TI  - Effects of reducing sympathetic activities on acute myocardial ischemia in cats.
AB  - The importance of the sympathetic nervous system in the genesis of ventricular
      arrhythmias associated with acute myocardial ischemia (AMI) was assessed in
      urethane-chloralose anesthetized cats. AMI was created by a ligation of the left
      anterior descending coronary artery. All control cats developed ventricular
      tachyarrhythmia (VT), ventricular fibrillation (VF), bradycardia and hypotension,
      resulting in 50% mortality. In other groups the paramedian reticular nucleus
      (PRN) was intermittently stimulated to inhibit the sympathetic nervous system.
      Both sides of the stellate ganglia (SG) or adrenal glands (AG) were removed to
      exclude direct effects of cardiac sympathetic nerve or indirect effects of
      circulatory catecholamines from the adrenal medulla on the heart, respectively.
      AMI did not affect plasma norepinephrine (NE) and epinephrine (EPI)
      concentrations in all groups. However, NE concentration was higher in SG removed
      but lower in AG removed group. Removal of SG and stimulation of PRN significantly
      reduced arrhythmia score and the incidence of VT, VF and mortality. Removal of AG
      appeared to be less effective. These findings suggest that cardiac sympathetic
      innervation is more important than neural and adrenal catecholamine secretions in
      the plasma.

PMID- 8287714
TI  - Chronic morphine treatment diminished ethanol mediated responses in the CNS.
AB  - The purpose of present experiment was to investigate the pharmacological effects
      of ethanol on morphine tolerant rats. We found that chronic morphine injection
      diminished the duration of ataxia induced by ethanol in rats. Using enzymatic and
      spectrophotometric methods, we found that chronic injection of morphine did not
      affect the metabolism of ethanol. On the other hand, the sensitivity to ethanol
      was decreased in the cerebellar Purkinje neurons. These suggested that behavior
      tolerance to ethanol in chronic morphine treated rats may possibly involve the
      desensitization of ethanol in the CNS.

PMID- 8287715
TI  - Protein kinase C activation facilitates memory retention in rats.
AB  - We have previously found that intra-hippocampal injection of H7, a protein kinase
      inhibitor, impairs memory retention in rats in a one-way passive avoidance
      learning task. It also decreases the optical density of several hippocampal
      protein bands on SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The present
      study examined whether protein kinase C (PKC) and phosphorylation of its
      substrate protein are involved in the memory process. The same behavioral
      paradigm was used. The infusion volume was 0.8 microliter each side throughout
      all experiments. We have microinjected phorbol ester (TPA), a specific PKC
      activator, into the dentate gyrus (DG) of hippocampus immediately after training.
      Animals were subject to the retention test 24 hr after training. Results revealed
      that TPA enhanced retention performance and protein phosphorylation in rats in a
      dose-response fashion with doses at 0.8 and 2.0 ng reaching a significant
      behavioral effect. The high dose of TPA also increased phosphorylation of four
      protein bands in the cytoplasma with molecular weight (MW) around 48 kDa, 60 kDa,
      78 kDa and 116 kDa, respectively; and seven protein bands in the membrane with MW
      around 38 kDa, 43 kDa, 48 kDa, 80 kDa, 88 kDa, 130 kDa and 210 kDa, respectively.
      In different animals, we have microinjected staurosporine, a specific PKC
      inhibitor, into the DG of hippocampus. Results indicated that at the low dose
      (0.5 ng), staurosporine was without a significant effect. At the middle and high
      doses (2.0 and 8.0 ng), it markedly impaired retention performance.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8287716
TI  - A primary cell-culture system for physiological studies of adrenocortical
      function.
AB  - We used guinea-pig adrenal tissue to develop a primary culture, enriched with
      zona fasciculata (ZF) cells. In a continuous culture up to 2 weeks, the cells
      maintained the characteristic of glucocortical function by producing cortisol as
      the final steroidogenic product and secreting it into culture medium. When
      culture medium, which was replaced at 24-hr intervals, was assayed for cortisol,
      the basal steroidogenic function peaked on day 5 and then declined. In response
      to 24-hr treatment with the bioactive adrenocorticotropic hormones (ACTH) on day
      4, production of cortisol was stimulated and prolonged, and also cells were
      morphologically hypertrophic. This in vitro system provides a convenient
      laboratory method which can be used for studying adrenocortical function under a
      possibly physiological condition.

PMID- 8287717
TI  - Vascular contractile properties in hypertension. I. A study of testing methods.
AB  - Abnormal contractile responses of blood vessels are observed widely in several
      hypertension models and are assumed to play a role in the etiology of essential
      hypertension. Inconsistent reports also exist due to different animals,
      preparations, and experimental techniques employed. In this investigation, we
      compared vascular response of normotensive Wistar-Kyoto rat (WKY) with that of
      spontaneously hypertensive rat (SHR) employing two experimental methods. Thoracic
      aorta obtained from age-matched animals were contracted by norepinephrine (NE)
      with either--single-dose method or cumulative-dose method. Differences in both
      reactivity (maximal tension) and sensitivity (ED50) to NE were observed. Although
      no significant differences were found between WKY and SHR with either method, the
      choice of the method employed could affect the outcome. For aorta from WKY, the
      reactivity to NE was similar for both methods; however, for aorta from SHR, the
      reactivity obtained by cumulative-dose method was significantly higher.
      Furthermore, the cumulative-dose method yielded higher sensitivity in both WKY
      and SHR when compared with that obtained by single-dose method. Taken together,
      the cumulative-dose method appeared to be a more sensitive method to determine
      contractile response. Nevertheless, no significant difference in either
      reactivity or sensitivity to NE in aorta was detected between WKY and SHR when
      cumulative-dose method was employed. These data indicate that aorta do not
      exhibit abnormal response to NE in SHR, consistent with earlier findings that not
      all tissue preparations behave similarly.

PMID- 8287718
TI  - [Pregnancy after cardiac valve replacement: analysis of 21 cases].
AB  - A retrospective analysis of 21 cases with 23 pregnancies after cardiac valve
      replacement from August 1979 to March 1992. In 11 cases mechanical and in 10
      biological valves were used, and in 18 cases with mitral valve replacement was
      done (MVR), in 1 case aortic valve replacement (AVR) and in 2 cases, both MVR and
      AVR were carried out 22 pregnancies in 20 cases with cardiac function grading I
      and II (New York Heart Association, NYHA) before pregnancy resulted in normal
      term deliveries and 1 case with grading III prior to pregnancy died of heart
      failure in the third trimester. All the cases treated with mechanical valve
      replacement received warfarin derivatives throughout pregnancy, and no
      malformation was found in their neonates. Issues related to pregnancy after
      cardiac valve replacement were discussed.

PMID- 8287719
TI  - [Calcium metabolism in normal pregnancy and pregnancy induced hypertension].
AB  - The concentration of serum calcium (Ca), phosphorus (P), alkaline phosphatase
      (AKP), parathyroid hormone (PTH) and calcitonin (CT) of 66 healthy pregnant women
      were measured at 2nd trimester, full term, 3 days and 6 weeks postpartum. These
      parameters were also measured in 56 patients with moderate or severe PIH in late
      pregnancy. The results showed that in spite of the obvious changes observed in
      these parameters at various periods, regulatory system of calcium metabolism in
      normal pregnancy was not affected. By contrast, calcium metabolism imbalance was
      seen in patients with moderate and severe PIH. The occurrence of PIH between two
      groups of pregnant women (50 each) with or without calcium supplement was
      compared. The pattern of calcium metabolism in normal pregnancy was summarized,
      and the pathogenesis of PIH related to calcium metabolism was discussed. The
      study provides an important basis for calcium supplementation during pregnancy
      and for using calcium antagonists to treat PIH patient.

PMID- 8287720
TI  - [Clinical significance of changes in ophthalmic arterial flow in pregnancy
      induced hypertension monitored by color Doppler imaging].
AB  - Ophthalmic arterial flow parameters were measured by color doppler imaging in 30
      cases of healthy non-pregnant women, 30 cases of normal pregnancy and 37 cases of
      pregnancy induced hypertension (PIH), together with left ventricular output
      determination. An elevation of 2nd peak, B/A ratio and all parameters but RI was
      recognized as the characteristics of ophthalmic arterial flow spectrum in PIH. A
      positive correlation was observed between these changes and severity of PIH. All
      parameters returned to normal as PIH was controlled either after treatment or
      after delivery. Ophthalmic arterial flow monitoring might be useful in diagnosis
      of PIH (sensitivity 82%, specificity 98%). and for prognosis of PIH.

PMID- 8287721
TI  - [Clinical evaluation of fetal blood flow velocity in cerebral artery and
      umbilical artery by color Doppler imaging].
AB  - Fetal cerebral blood flow velocity waveforms were examined by color Doppler
      imaging. The results showed that the ratio of fetal middle cerebral artery
      resistance index (RImca) to umbilical artery resistance index (RIua) in normal
      late pregnancy was greater than 1 (RImca/RIua > 1). It was negatively correlated
      with blood pressure in pregnancy induced hypertension (PIH). It indicated that
      RIua increased gradually in PIH and RImca decreased when cerebral vessel damage
      occurred. RImca/RIua ratio < 1 in PIH patient has higher prognostic value for
      perinatal outcome than umbilical artery flow velocity waveform alone. The
      positive likelihood ratio is 25.97, and the negative likelihood ratio is 0.15.

PMID- 8287722
TI  - [Clinical analysis of the relation between maternal body weight and high risk
      factors during pregnancy and delivery].
AB  - The incidence of pregnancy induced hypertension (PIH), prolonged pregnancy,
      prolonged labor, macrosomia and the rate of operative delivery were analysed in
      76 overweight women and in 436 women with normal body weight admitted at the same
      period to the hospital. The results showed that the occurrence of risk factors
      mentioned above was significantly higher in the overweight group, particularly in
      those with excessive weight gain during pregnancy than that of normal weight
      group (P < 0.001-0.05). To reduce high risk pregnancy, operative delivery,
      perinatal mortality and morbidity in overweight women especially associated with
      excessive weight gain during pregnancy the importance of perinatal care with
      nutritional advice is evident.

PMID- 8287723
TI  - [Effects of maternal intravenous glucose administration at term or shortly before
      cesarean section on fetus].
AB  - In order to investigate the effects of maternal intravenous glucose
      administration on fetus, two groups of pregnant women were observed. In the first
      group, 33 cases in late pregnancy, who received 50% glucose 80ml by intravenously
      injection. The mean fetal heart rate and fetal movements were found to be
      increased, maternal and fetal blood glucose levels elevated; umbilical artery pH
      decreased after the administrations as compared with the control group. The
      results indicated that a single injection of glucose at term had no adverse
      effect on fetus. In the second group 23 cases who received glucose 10% 400ml by
      intravenous drops shortly before CS, subclinical fetal acidosis was mated.
      Therefore, glucose given in this way should be employed cautiously, and rapid
      intravenous infusion should be avoided.

PMID- 8287724
TI  - [Methotrexate-citrovorum factor individualized reduced dose therapy for ectopic
      pregnancy: report of 20 cases].
AB  - In twenty patients with ectopic pregnancy who received treatment using
      methotrexate-citrovorum factor in an individualized reduced dose regimen 17 cases
      were successfully treated, 4 required one course of therapy, 8 required two
      courses, 4 required three courses, only 1 required four courses, according to the
      difference in the speed of hCG reduction. The success rate was 85.0%, two cases
      got intrauterine pregnancy within 6 months after the treatment. Three ruptured
      cases during treatment were operated upon. The pathologic findings at the ectopic
      site were chorionic bleeding, necroses, with dissolution of trophoblastic cells.

PMID- 8287725
TI  - [The amplification of c-myc, N-ras, c-erb B oncogenes in ovarian malignancies].
AB  - In this study, [a-32p]dATP labelled probes of c-myc, N-ras and c-erb B genes were
      employed to perform dot blot hybridisation with DNA extracted from 17 cases of
      primary ovarian cancer, 3 cases of recurrent ovarian cancer, 2 cases of germ cell
      ovarian cancer, 5 cases of serous cysadonoma and 4 cases of normal ovarian
      tissue. Some specimens were examined by Southern blot hybridisation. The results
      showed varying degrees of amplification: c-myc 54.5%, N-ras 64.1% and c-erb B
      31.8%, in the 22 cases of ovarian malignancies. All were significantly higher
      than in the three benign tumours and in normal ovarian tissue. Frequency of
      amplification of more than 2 oncogencis at the same time was found to be 40.9%.
      There was a negative correlation between amplification of c-myc and
      differentiation. A relatively high amplification of N-ras was present in late
      stage ovarian cancer. Patients with c-erb B amplification showed a shorter
      survival period than those without amplification.

PMID- 8287726
TI  - [AgNOR of gastational trophoblastic tumors and its clinical significance].
AB  - A total of 120 paraffin-embedded gestational trophoblastic tumor tissue blocks
      was selected and divided into 5 groups: (1) 20 cases of normal chorionic villi.
      (2) 40 cases of hydatidiform mole with no malignant change during a following-up
      period of at least two years. (3) 40 cases of hydatidiform mole which developed
      into invasive mole or choriocarcinoma. (4) 10 cases of invasive mole. (5) 10
      cases of choriocarcinoma. Nucleolar organizer regions (NORs) was Ag-stained and
      AgNOR dots were counted using the Plotion's method. The result showed that there
      was significant difference between group 1 and group 2 (P < 0.005), group 2 and
      group 3 (P < 0.001), group 3 and group 4 (P < 0.05). Taking the AgNOR count 4.00
      as a standard, 75% of the cases in group 2 (mean = 2.730) was below this
      standard. The study suggested that with the increase of malignancy of
      trophoblastic tumor, the AgNOR count increased correspondingly. A quantitative
      study of AgNOR might be a useful measure to detect the early malignant change of
      hydatidiform mole.

PMID- 8287727
TI  - [Selective salpingography and tubal cannulation through hysteroscopy].
AB  - In this paper the procedure of selective salpingography and tubal cannulation
      through hysteroscopy for diagnosis and treatment of fallopian tube obstruction at
      the interstitial portion was introduced. We combined hysteroscopic tubal
      cannulation with selective salpingography under fluoroscopic quidance in 28
      infertile women with 49 obstructed interstitial portion of fallopian tubes
      diagnosed previously. After the procedures 27 tubes (55.1%) became patent in 16
      cases. In 16 women with patent tubes followed up over 6 months after the
      procedures 5 intrauterine pregnancies occurred. This procedure is a safe and
      simple diagnostic method to identify fallopian tube obstruction at the
      interstitial portion and may alos serve as a therapeutic approach in some of
      these patients.

PMID- 8287728
TI  - [Clinico-pathological staging of endometrial carcinoma and the evaluation of
      methods for assessing myometrial invasion in clinical stage I cases].

PMID- 8287729
TI  - [Diagnosis and treatment of HELLP syndrome].

PMID- 8287730
TI  - Flow cytometric DNA analysis of wheat-rye addition lines.
AB  - The nuclear DNA content of the 7 wheat-rye chromosome addition lines were
      determined by flow cytometry. The nuclear DNA content of each line was compared
      to the original wheat parental line. From this information, the amount of DNA per
      rye chromosome was calculated. The DNA per chromosome ranged from 0.8 picograms
      (pg) in chromosome 3R to 1.4 pg in chromosome 7R. Flow cytometry was proven to be
      a rapid and reliable technique for the evaluation of aneuploid plant populations.
      Flow cytometry has the potential to allow for more rapid screening of aneuploid
      and euploid cytological stocks than conventional cytogenetic techniques.

PMID- 8287731
TI  - Germinal center analysis with the tools of mathematical morphology on graphs.
AB  - Only few studies devoted to quantitative analysis of tissue architecture have
      been performed. The analysis of neighborhood relationships between cells, using
      graphs and mathematical morphology (MM), constitutes one approach. We propose to
      analyse quantitatively the architecture of a tissue with the tools of MM on
      graphs. The use of graphs seems best suited to take into account the neighborhood
      relationships between cells, independently from their mutual distances: two cells
      are considered as neighbors if no interfering cell is placed in a given sense
      between them. Such neighboring cells are linked by an arc in a graph. On such a
      graph, all tools of MM may be applied. We investigate two of them in the present
      work: (1) the distance transforms permits to analyse the repartition of a
      cellular population A relative to population B, (2) the size distribution permits
      to analyse the tendancy of a cell population to form clusters. We have applied
      this method using Gabriel's graph, derived from the Voronoi diagram, to determine
      the "zone of influence" of a cell. We have analysed the neighborhood
      relationships between cells in germinal centers (GC) from lymph nodes. Twelve
      hyperplastic GCs from follicular hyperplasia (FH) and 5 neoplastic GCs from small
      cleaved cell follicular lymphoma (++SCCFL) have been studied; 2 microns
      hematoxylin-eosin plastic embedded sections have been analysed. Cell nuclei have
      been identified manually by the observer by giving a numerical and image color
      code. Gabriel's graphs have been constructed with all centrofollicular cells.
      Subgraphs with only lymphoid cells, large cells or small cleaved cells have also
      been studied. The application of MM transformations on the graphs using software
      package Morphograph has allowed a quantitative description of cell distribution
      in the tissue. The distances of centrofollicular lymphoid cells from the
      periphery of the GCs (mantle zone), from nonlymphoid cells as macrophages located
      within the GCs and between large lymphoid cells and small lymphoid cells have
      been determined in FH and SCCFL. Using iterative closings and openings, we have
      detected aggregates of small and large cells and characterized their size and
      distribution in the GCs. The application of this method on lymph node biopsy has
      allowed a quantitative description and comparison of GCs in different
      pathological conditions.

PMID- 8287732
TI  - Optimal detection of apoptosis by flow cytometry depends on cell morphology.
AB  - Flow cytometry has recently become a choice technique for the quantitative
      analysis of apoptosis. Monoparametric DNA analysis usually allows identification
      of apoptotic cells as a "subdiploid" peak. Progression through apoptosis leads to
      chromatin condensation, nuclear fragmentation and eventually to cell disruption.
      Thus, a major problem for the flow cytometric analysis of apoptotic populations
      is discrimination between debris and apoptotic cells. Here we demonstrate that
      the best parameter on which to make such a distinction is the DNA content, no
      matter what type of cell is studied. In contrast, discrimination between
      apoptotic, non-apoptotic cells, and debris is possible on the basis of scattering
      signals only in few selected cases, depending on the morphology of the intact
      cells.

PMID- 8287733
TI  - Quantitation of adhesion molecules and other function-associated antigens on
      human peripheral blood leucocytes.
AB  - Quantitating satisfactorily the expression of adhesion molecules and other
      functional antigens on the surface of human peripheral blood granulocytes by flow
      cytometry is difficult. Artefactual (in vitro) changes, which occur in the
      expression of these molecules during conventional cell preparation and labelling
      procedures, led to the development of a leucocyte preparation technique that
      prevents upregulation of the leucocyte integrins and other antigens. The
      technique, as originally evaluated, involves fixing freshly drawn blood with
      formaldehyde (final concentration 0.2%) for 4 min at 37 degrees C before adding
      ammonium chloride to lyse the erythrocytes; procedures which are inconvenient
      when blood samples are taken in wards or clinics that are some distance from a
      laboratory. We therefore investigated i) whether blood could be kept with
      commonly used anticoagulants for up to 1 h before fixation, and ii) whether
      unanticoagulated blood could be kept with formaldehyde for a similar period
      before processing was continued. The results showed that when quantitating those
      granulocyte surface antigens which can be rapidly upregulated: i) that it is
      preferable to mix freshly drawn unanticoagulated blood directly with
      formaldehyde; ii) that if blood must be collected into anticoagulants, it should
      be kept for only the briefest possible time before processing; and iii) that the
      time for which cells are exposed to 0.2% formaldehyde must be carefully
      controlled and limited to 4 min. A corollary of the results with anticoagulants
      is that it is probably impossible to isolate live granulocytes by currently
      available procedures without artefactually altering the expression of these
      antigens in vitro.

PMID- 8287734
TI  - Measurement of intracellular pH using flow cytometry with carboxy-SNARF-1.
AB  - The new intracellular pH (pH(i)) dye carboxy-seminaphthorhodafluor (SNARF-1) was
      compared to the established dye 2,3-dicyanohydroquinone (DCH) using flow
      cytometry. Both dyes give high-resolution pH(i) measurements. SNARF-1 remains
      trapped within cells much longer than DCH, so that pH(i) can be monitored during
      and after treatments with chemicals or hyperthermia. The toxicity of the dyes is
      similar, and both dyes can be used at concentrations that result in low toxicity
      to cells. Adequate staining of cells with SNARF-1 is dependent on the cell
      concentration. The absolute pHi values indicated by SNARF-1 are higher than
      values measured with DCH. However, the trends measured by both dyes are
      consistent, and both are useful for making pH(i) measurements.

PMID- 8287735
TI  - Development and optimization of tissue preparative methodology for DNA content
      analysis of soft tissue neoplasms.
AB  - Data regarding DNA content parameters in soft tissue sarcoma is limited.
      Development and optimization of tissue specific preparative techniques for DNA
      flow cytometry was undertaken prior to routine DNA content analysis of soft
      tissue neoplasms; 154 soft tissue tumors were studied. Dissociation dependent
      differences in cellular yields, viabilities, maintenance of DNA aneuploid
      populations, coefficients of variation, and DNA index supported the need for
      these developmental studies. Fifty-six of eighty-nine patients had DNA aneuploid
      soft tissue sarcomas. A relationship between DNA aneuploidy and grade was seen in
      this series with 38% with low grade, 59% with moderate grade, and 69% with high
      grade tumors demonstrating DNA aneuploid populations (P < 0.005). The mean S
      phase fraction for DNA diploid and aneuploid sarcomas was 7.2% and 13.3%,
      respectively (P < 0.001). When classified by histologic grade of the primary
      tumor, a greater percentage of metastatic lesions were DNA aneuploid (4 of 7
      grade 2 lesions, and 15 of 16 grade 3 lesions). Decreases in cellular yields and
      rate of DNA aneuploidy were observed in a subgroup of patients with localized
      high grade sarcoma treated preoperatively, as compared to patients treated with
      initial surgery. Prospective correlation of DNA content parameters to prognosis
      and response to cytotoxic therapy are now possible and are ongoing.

PMID- 8287736
TI  - Improved method for release of cell nuclei from paraffin-embedded cell material
      of squamous cell carcinomas.
AB  - An improved method of releasing cell nuclei from paraffin-embedded highly
      keratinized squamous cell carcinomas by pretreatment with 85% formic acid-0.3%
      H2O2 followed by enzymatic treatment with subtilisin Carlsberg is described.
      After DAPI staining the resulting suspensions of cell nuclei were analyzed by DNA
      flow cytometry, in addition to microscopy. The total yield of released cell
      nuclei was improved and the proportion of tumor cell nuclei in the suspensions
      increased from 12% to 53% using this method compared to the conventional
      preparation technique. Cytoplasmic residue disappeared nearly completely. Thus,
      the finding of false aneuploid cell populations representing diploid cells with
      autofluorescent cytoplasm could be avoided. In addition, even small true
      aneuploid cell populations could be detected due to the increased proportion of
      released tumor cell nuclei and the lower proportion of background in the > 2C
      region.

PMID- 8287737
TI  - Flow and image cytometry for DNA analysis in bladder washings: improved
      concordance by using internal reference for flow.
AB  - Using flow or image cytometry, we compared the DNA distribution of cells from
      bladder washings from 52 patients with bladder cancer. For image cytometry,
      urothelial nuclei (recognized visually) were analyzed for DNA content using
      polymorphonuclear nuclei as internal diploid reference. For flow cytometry, two
      methods can be used: either all cells can be analyzed, as commonly performed, or
      urothelial cells can be analyzed alone, after specific detection. In this flow
      cytometry study, cells were doubly stained for panurothelial antigens T16 and for
      DNA. All the cells were first analyzed using peripheral lymphocytes as an
      external reference; 79% of the results were similar with results obtained from
      image analysis. For discordant results, flow-cytometric data were reprocessed to
      identify immunologically stained urothelial cells; one additional case became
      concordant with image cytometry when only urothelial cells were analyzed, with
      lymphocytes as diploid reference; a better concordance (94%) was found when the
      nonurothelial cells of the samples served as a diploid reference instead of
      peripheral lymphocytes. This suggests that we achieved an improvement of the flow
      cytometric evaluations for ploidy assessment, and we conclude that, on these
      conditions, flow or image analysis can be considered as equivalent methods for
      DNA content studies of tumors.

PMID- 8287738
TI  - Subtraction of autofluorescent dead cells from the lymphocyte flow cytometric
      binding assay.
AB  - Flow cytometry allows the quantitative analysis of lymphocyte-target cell
      conjugates and the identification of the lymphocyte subset involved in the
      binding phenomenon. We recently described a methodology to identify the effector
      cells bound to K562 targets based on target cell autofluorescence coupled with
      lymphocyte staining by means of fluorescent monoclonal antibodies. Here we
      describe an implementation of the methodology that allows the subtraction of
      spontaneously dead targets to which lymphocytes may or may not adhere, thereby
      preventing the overestimation of the binding phenomenon and limiting its
      evaluation to living effector-target conjugates, thus preserving the specificity
      of the phenomenon.

PMID- 8287739
TI  - The posterior sagittal approach: implications in adult colorectal surgery. Harry
      E. Bacon Lectureship.
AB  - Posterior sagittal anorectoplasty was used for the first time in 1980 to treat
      anorectal malformations. This approach includes a wide exposure, through a
      midline posterior incision, to determine the limits of the sphincteric mechanism
      and to place the rectum within its limits. This approach has been used to treat
      children with anorectal malformations, who underwent conventional procedures that
      failed. The management of anorectal malformations with this approach rendered
      significantly better results in terms of bowel control. However, there is still a
      large number of patients suffering from fecal incontinence and for them a bowel
      management program was designed to improve their quality of life. The posterior
      sagittal approach was also used for the treatment of acquired conditions
      including tumors, post-trauma and postradiation fistulas, and other postoperative
      complications. A historic review of the posterior approach disclosed that Cripps,
      a British surgeon, published his experience with a posterior transsphincteric
      approach to the rectum nine years before Kraske, a German surgeon, whose name has
      been traditionally associated with the leadership in this approach. Kraske
      actually approached the rectum through a paramedian incision and never performed
      a real transsphincteric incision. An experimental study done in dogs by the
      author demonstrated that it is not harmful to divide the sphincteric mechanism.
      The posterior sagittal approach represents a useful alternative to treat many
      pelvic conditions and, therefore, it must be a part of the armamentarium of
      colorectal surgeons. Finally, a series of clinical experiences convinced the
      author that coordinated rectosigmoid motility is the most important single factor
      in fecal continence and, therefore, our efforts to help patients suffering from
      fecal incontinence must be aimed at the manipulation of bowel motility.

PMID- 8287740
TI  - Colonic anastomoses: bursting strength after corticosteroid treatment.
AB  - PURPOSE: This study was designed to determine the effect of corticosteroids on
      healing colonic anastomoses. METHODS: Bursting pressure measurements were
      performed on 108 male albino rats receiving corticosteroid treatment. Twelve
      animals were sacrificed at time zero to determine the bursting pressure of
      nonoperated, nonsteroid-treated colon. The remaining 96 animals underwent
      division and reanastomosis of their midtransverse colon. They were then separated
      into four groups of 24 each. Twelve animals in each group received steroid
      treatment while the remaining 12 acted as controls. The groups were sacrificed at
      4, 6, 8, and 20 days. The bursting pressures of the anastomoses were then noted.
      RESULTS: There was no significant difference in bursting strength between treated
      animals and controls at four days (P = 0.27). A significant difference occurred
      at 6, 8, and 20 days (P = 0.01, 0.003, 0.009, respectively). The colonic bursting
      pressure of operated controls returned to that of a normal, nonoperated colon by
      20 days. CONCLUSION: This study demonstrates that steroids do have an adverse
      effect on colonic anastomotic healing.

PMID- 8287741
TI  - Postoperative recurrence in patients with intestinal Behcet's disease.
AB  - PURPOSE: The postoperative course of intestinal Behcet's disease was studied in
      nine patients who had undergone a total of 15 operations due to intestinal
      ulcers. METHODS: These patients were followed up for an average of 6.0 years
      (range, 1 year, 3 months to 13 years, 10 months) after each operation and they
      were repeatedly examined by double-contrast radiography and/or colonofiberscopy.
      RESULTS: Recurrence of intestinal ulcers was observed in 12 (80 percent) of the
      15 surgical cases. The incidence (50 percent) of postoperative recurrence in six
      cases in which intraoperative endoscopy revealed no abnormality in the retained
      intestine was lower than that (100 percent) in nine cases without this
      examination. Recurrent intestinal lesions in most cases were demonstrated as
      multiple aphthoid ulcers in the ileum near the ileocolectomy, or as one or two
      deep ulcers at the ileocolectomy site. The recurrent ulcers were successfully
      treated by various medical therapies, but the effectiveness of these therapies
      was only temporary. CONCLUSION: In the case of this disease, intraoperative
      endoscopy may be useful for preventing postoperative recurrence and periodic
      follow-up examination with radiography and endoscopy should be performed, even
      after surgery.

PMID- 8287742
TI  - Serum gastrin values in patients with familial adenomatous polyposis.
AB  - PURPOSE: An evaluation of the importance of gastrin in the colorectal
      carcinogenesis in patients with familial adenomatous polyposis was conducted.
      METHODS: Blood samples from 168 family members of 26 families were investigated
      for circulating gastrin. Blood was drawn from 65 affected patients, 66 clinically
      unaffected first-degree relatives, and 37 spouses. RESULTS: We did not find any
      difference in distribution of serum gastrin among these groups. CONCLUSION: Our
      results seem to exclude gastrin from being relevant in early carcinogenesis in
      patients with familial adenomatous polyposis.

PMID- 8287743
TI  - Histologic and microbiologic features of biopsy samples from patients with normal
      and inflamed pouches.
AB  - PURPOSE: This study was undertaken to assess the electron microscopic and
      microbiologic findings in tissue biopsy samples from patients with pouchitis and
      to compare them with findings in patients with normal pouches, conventional
      ileostomies, and normal ileum. METHODS: Tissue samples were obtained from 78
      patients: 23 patients with normal pouches endoscopically and histologically
      (Group 1), 12 patients with endoscopic and histologic evidence of inflammation
      (pouchitis) (Group 2), 14 patients who had either endoscopic or histologic
      evidence of inflammation but not both (Group 3), 20 patients with conventional
      ileostomies (Group 4), and 9 patients without ileostomies from whom biopsy
      samples of normal ileum were obtained (Group 5). RESULTS: The mean total aerobic
      facultative counts in the biopsy samples from the pouchitis patients were
      significantly higher when compared with biopsy samples from Groups 4 and 5 (P <
      0.05). There were no significant differences in the mean anaerobic counts among
      the five groups. Positive cultures were obtained in 90 percent of patients with
      pouches compared with 69 percent of patients with conventional ileostomies or
      normal ileum (P < 0.05). Intramural bacteria were observed on electron microscopy
      in biopsy specimens of 47 percent patients with pouches compared with 14 percent
      of patients with conventional ileostomies or normal ileum (P < 0.05). However,
      the proportion of patients with positive cultures or intramural bacteria was not
      increased in the pouchitis group compared with the normal pouch group.
      CONCLUSION: These data suggest that intramural aerobic facultative bacterial
      counts are elevated in patients with pouchitis and may play a role in the
      pathogenesis of pouchitis.

PMID- 8287744
TI  - Internal anal sphincter activity after restorative proctocolectomy for ulcerative
      colitis: a study using continuous ambulatory manometry.
AB  - PURPOSE: The aim of this study was to further investigate continuous ambulatory
      anal manometry which has recently been introduced as a method for studying
      anorectal activity in ambulant patients, thereby avoiding many of the potential
      drawbacks of static techniques. METHOD: In this study continuous ambulatory
      manometry was used to assess the activity of the internal anal sphincter in
      patients who had undergone restorative proctocolectomy, and, in particular, to
      compare patients who had undergone conventional mucosal proctectomy with sutured
      endoanal, ileoanal anastomosis with patients who had undergone restorative
      proctocolectomy with preservation of the entire anal canal by means of stapled,
      end-to-end, ileoanal anastomosis without mucosectomy. RESULTS: Evidence of basal
      internal sphincter activity was found in only 38 percent of patients after
      mucosal proctectomy with sutured endoanal anastomosis, whereas all patients after
      restorative proctocolectomy with stapled end-to-end anastomosis and all control
      individuals showed such activity of the internal sphincter. Similarly, the number
      of sampling episodes seen in patients after mucosal proctectomy with endoanal
      anastomosis was significantly less (median, 0.0/hours (0-30/hours)) than the
      number of sampling episodes observed in patients after end-to-end anastomosis
      (median, 4.5/hours (1-48/hours)) or in control individuals (median, 5.6/hours (0
      31/hours)) (P < 0.001). CONCLUSIONS: These results suggest that the internal anal
      sphincter is damaged in the course of mucosal proctectomy and endoanal
      anastomosis. In contrast, after restorative proctocolectomy with stapled, end-to
      end anastomosis normal function of the internal sphincter is preserved.

PMID- 8287745
TI  - Multiple hemorrhoidal bandings in a single session.
AB  - PURPOSE: The aim of our study was to evaluate the risks of multiple hemorrhoidal
      bandings in a single session. METHODS: We retrospectively examined all of the
      patients who had hemorrhoidal bandings from July 1989 to August 1992. RESULTS:
      Patients with multiple hemorrhoidal banding in a single session when compared
      with patients with single banding had greater discomfort and pain (29 percent vs.
      4.5 percent), but this discomfort was usually manageable with oral analgesia of
      limited duration. There were also more vasovagal symptoms (5.2 percent vs. 0
      percent), local swelling and edema (2.6 percent vs. 0 percent), and urinary
      hesitancy and frequency (12.3 percent vs. 0 percent) in the multiple-banded
      patients. No major complication such as massive delayed bleeding and perineal or
      pelvic sepsis was noted. CONCLUSION: Most patients tolerated multiple
      hemorrhoidal banding in a single session with acceptably low complications.
      Multiple banding in a single session is a safe and cost-effective alternative.

PMID- 8287746
TI  - The importance of anal endosonography in the evaluation of idiopathic fecal
      incontinence.
AB  - PURPOSE: The aim of the study was to evaluate the use of anal endosonography in
      idiopathic incontinence. METHODS: In 29 patients and 26 normal controls, the
      relationship between sonography images and physiologic parameters was studied.
      RESULTS: External anal sphincter function, measured as fiber density by single
      fiber electromyography (P = 0.0001) and pudendal nerve terminal motor latency (P
      = 0.04), was significantly impaired in patients with idiopathic incontinence
      compared with controls. Both the external and internal and sphincter could be
      identified by anal endosonography, and the thickness directly measured. The
      thickness of the external anal sphincter was significantly negatively correlated
      to muscle fiber density (r = -0.65, P = 0.002) and to pudendal nerve distal
      conduction velocity (r = -0.74, P = 0.008). The thickness of the internal anal
      sphincter was significantly correlated to resting pressure (r = -0.67, P =
      0.0001). CONCLUSION: The ratio between the thickness of the external and internal
      sphincter muscles measured on the sonography screen was significantly reduced in
      patients with neurogenic incontinence compared with controls (P < 0.01).

PMID- 8287747
TI  - Diagnostic value of C-reactive protein in acute appendicitis.
AB  - Serum C-reactive protein was measured in 56 patients hospitalized with a
      suspected diagnosis of acute appendicitis. Based on these determinations, four
      groups of patients were defined: Group A = 26 patients with acute appendicitis
      who had a C-reactive protein level higher than 2.5 mg/dl. Group B = 4 patients
      with a C-reactive protein level lower than 2.5 mg/dl who, after surgery based on
      a presumed diagnosis of acute appendicitis, were found to have a normal appendix.
      Group C = 22 patients with nonspecific abdominal pain, 18 (72 percent) of whom
      had an elevated C-reactive protein level, although in only 4 (7.1 percent) were
      these levels higher than 2.5 percent mg/dl. Group D = 4 patients who had diseases
      other than acute appendicitis. It is concluded that an increase in C-reactive
      protein levels to more than 2.5 mg/dl is not a definite indicator of acute
      appendicitis. However, if the C-reactive protein level in blood drawn 12 hours
      after the onset of symptoms is less than 2.5 mg/dl, acute appendicitis can be
      excluded.

PMID- 8287748
TI  - Predicting lymph node metastases in rectal cancer.
AB  - For properly selected rectal cancers, local excision is a sphincter-saving
      alternative to abdominoperineal resection. If histologic assessment of a locally
      excised tumor reveals ominous features, further treatment with radical resection
      or irradiation may be necessary to treat potential lymph node metastases.
      PURPOSE: We wished to determine which features, if any, were predictors of nodal
      metastases. METHODS: Nine histologic and morphologic features of 62 radically
      excised rectal cancers were reviewed to determine which factors, if any, were
      associated with nodal disease. RESULTS: Using a chi-squared analysis, we found
      worsening differentiation (P = 0.0001), increasing depth of penetration (P =
      0.026), a microtubular configuration of 20 percent or more (P = 0.023), and the
      presence of venous (P = 0.001) or perineural invasion (P = 0.002) to
      significantly influence nodal disease. Lymphatic invasion was witnessed too
      infrequently to determine significance but, when present, was associated with
      nodal metastases in every case. Exophytic tumor morphology, mitotic count, and
      tumor size were not significant predictors. An analysis of variables determined
      that, of all factors or combination of factors examined, Broder's classification
      was the strongest predictor of nodal disease. CONCLUSIONS: If a rectal cancer is
      accessible and of small size to facilitate local excision, an in-depth histologic
      assessment is needed to determine if nodal metastases are likely on a statistical
      basis.

PMID- 8287750
TI  - Surgical treatment of cytomegalovirus enterocolitis in severe human
      immunodeficiency virus infection. Report of eight cases.
AB  - PURPOSE: The aim of this study was to describe our experiences of surgical
      removal of inflamed bowel in cytomegalovirus enterocolitis. METHODS: Eight
      homosexual males with a mean age of 41 years (range, 29-59 years) and a mean CD4
      count of 21 x 10(6)/l (1-60 x 10(6)/l) with advanced human immunodeficiency virus
      infection and severe cytomegalovirus enterocolitis were treated with ileocecal
      resection (4 patients) or right-sided hemicolectomy (4 patients). Symptoms were
      lower abdominal pain, severe diarrhea, fever, and weight loss, unrelieved by
      anticytomegalovirus therapy. Radiologic examination showed that ulcerative
      inflammation was limited to the right colon and terminal ileum. Microscopic
      examination confirmed the cytomegalovirus enterocolitis. Intermittent
      cytomegalovirus treatment, usually with foscarnet for 10 to 14 days every 4 to 6
      weeks was given postoperatively. RESULTS: Two minor postoperative complications
      occurred: a lesser wound infection and a moderate bleeding from the abdominal
      wound edges. One patient died after three weeks because of gastrointestinal
      bleeding from an ulcerating Kaposi's sarcoma lesion and another patient died from
      unrelated causes three weeks after discharge from the hospital. The remaining 6
      patients experienced complete or partial palliation of the abdominal symptoms for
      a mean of 14 months (range, 5-35 months) until death or the end of observation
      time. One patient is still alive two years after the operation. The overall mean
      survival was 12 months (range, 0.5-35 months). Recurrent or persistent symptoms
      and/or signs of cytomegalovirus enterocolitis occurred in four patients after a
      mean of seven months. CONCLUSION: Resection of inflamed bowel combined with
      postoperative anticytomegalovirus treatment leads to excellent palliation and a
      relatively favorable survival in AIDS patients with cytomegalovirus
      enterocolitis.

PMID- 8287749
TI  - Intermittent therapy with high-dose 5-aminosalicylic acid enemas maintains
      remission in ulcerative proctitis and proctosigmoiditis.
AB  - PURPOSE: The aim of this study was to compare the efficacy of intermittent
      therapy with mesalazine enemas and continuous oral mesalazine to maintain
      remission of distal ulcerative colitis or proctitis. METHODS: Thirty-eight
      patients with distal ulcerative colitis (n = 17) or ulcerative proctitis (n = 21)
      in clinical, endoscopic, and histologic remission were randomly assigned to
      receive either oral mesalazine (0.5 g three times/day, Eudragit L coating, n =
      19) or intermittent therapy with mesalazine enemas (4 g of 5-aminosalicylic acid
      enema every third night, n = 19). Both groups were comparable in regard to sex,
      age, age at disease onset, extent and duration of disease, number and mode of
      treatment of previous attacks, and time in remission. Patients were reviewed at
      the beginning of the study and, subsequently, at two-month intervals for 24
      months or until a relapse occurred. At each visit, diaries were reviewed and
      clinical and laboratory assessments were performed. Sigmoidoscopy was carried out
      and biopsies were obtained by a blinded observer. Histology was assessed without
      knowledge of the patient's clinical state or treatment category. RESULTS: At the
      end of the study, 6 of 19 patients on oral mesalazine (32 percent) and 14 of 19
      patients on mesalazine enemas (74 percent) were still in full remission (log rank
      test: 15.28, P < 0.001). Differences in relapse rates between groups were
      significant even when data were stratified by extent of disease (P < 0.01). In
      the oral group, six and seven patients relapsed at 12 and 24 months,
      respectively. In the enema group, three and two relapses occurred in the first
      and second year of the study, respectively. All patients complied with the
      treatment satisfactorily and there were no dropouts. CONCLUSION: These results
      suggest that intermittent therapy with mesalazine enemas is more effective than
      continuous oral mesalazine in maintaining remission in patients with distal
      ulcerative colitis and proctitis.

PMID- 8287751
TI  - Radical abdominopelvic lymphadenectomy: historic perspective and current role in
      the surgical management of rectal cancer.
AB  - Radical abdominopelvic lymphadenectomy for rectal cancer is based on the tenet
      that removal of all potentially involved lymphatic tissue will yield a lower rate
      of locoregional failure and improve survival. At centers with extensive
      experience with the procedure, the operating time is only modestly prolonged
      compared with conventional resection. Blood loss and postoperative
      hospitalization are not significantly increased. Urinary dysfunction and
      impotence associated with radical abdominopelvic lymphadenectomy (as high as 80
      percent and 76 percent, respectively, in recent series) have been major
      deterrents to its more routine application. Preservation of the hypogastric
      plexus and even selective preservation of a unilateral S4 nerve root have been
      shown to reduce the occurrence of genitourinary complications. Improved five-year
      survival of 68 percent and local recurrence rates of 5 to 20 percent for TNM
      Stage III cancers have been achieved with radical abdominopelvic lymphadenectomy.
      These results compare favorably with recent trials of adjuvant chemoradiation
      after conventional resection in stage-matched patients. The rationale, evolution,
      and application of radical abdominopelvic lymphadenectomy to the surgical
      management of rectal cancer are critically examined. The potential benefits of
      radical abdominopelvic lymphadenectomy, which have been demonstrated in
      nonrandomized trials, should be evaluated in a prospective and properly
      randomized study to clearly establish or refute its efficacy.

PMID- 8287752
TI  - Intracavitary irradiation of early rectal cancer for cure. A series of 186 cases.
      1975.

PMID- 8287753
TI  - Medical malpractice involving colon and rectal disease.

PMID- 8287754
TI  - Nucleolar organiser regions of mesothelial and carcinomatous cells in effusions.
AB  - The AgNor reaction was performed on effusions and peritoneal washings, and the
      silver dots were counted on normal or reactive mesothelial cells vs.
      carcinomatous cells, ascertained by previous HE staining. The mean values were
      1.64 for the former (n = 20) and 4.90 for the latter (n = 10). The intersection
      between the two group distributions was 2.78, leaving a chance of only 0.65% for
      a false-positive result. The method may thus be helpful in the interpretation of
      doubtful cytological cases.

PMID- 8287755
TI  - Fine-needle aspiration cytology of silicone granulomas in the augmented breast.
AB  - We studied 12 aspirates from 10 patients who underwent diagnostic fine-needle
      aspiration cytology (FNAC) of an augmented or reconstructed breast. Six patients
      were augmented with silicone gel-filled implants and four patients had silicone
      liquid injections. FNAC indications included a painful or suspicious mass.
      Excisional biopsy was performed in six cases after FNAC. The findings of eight
      cases included modestly cellular smears composed of loosely cohesive histiocytes
      containing vacuoles of various sizes. Multinucleated foreign body giant cells,
      fragments of dense, amorphous fibrous tissue, and fibroblast nuclei stripped of
      cytoplasm were also present. Two patients showed a mixture of inflammatory cells
      characteristic of intramammary lymph nodes or lymphoid aggregates. We conclude
      that silicone granulomas of the breast show a characteristic set of findings on
      FNAC which enable a cytopathologist to render a specific diagnosis given an
      appropriate history of breast augmentation.

PMID- 8287756
TI  - Pericellular lacunae in effusions.
AB  - Pericellular lacunae are reported to be characteristic of adenocarcinoma cell
      clusters in cell block preparations of serous effusions. We examined the
      incidence of lacunae in cell blocks from 24 benign and 31 malignant effusions.
      The cases were classified as follows: group A with no pericellular lacunae, group
      B with < 50% of cell clusters in lacunae, and group C with > 50% of cell clusters
      in lacunae. Of the malignant effusions, 5% were in group A, 67% were in group B
      and 29% were in group C. Of the benign effusions, 50% were in group A, 50% were
      in group B, and 0% were in group C. The pericellular lacuna by itself is not a
      reliable diagnostic criterion. It could assist, however, in the overall evidence
      when evaluating a case, particularly if either there are no lacunae seen or the
      majority of cells are in lacunae. Furthermore, since lacunae are easily visible
      at low magnification, their recognition may help in screening cell blocks, using
      their presence to locate cell groups worthy of special attention.

PMID- 8287757
TI  - Cervical cytology findings in women infected with the human immunodeficiency
      virus.
AB  - It has been suggested that immunocompromised, HIV-infected patients are at risk
      of developing HPV infection and SIL. The well documented role of HPV and SIL in
      cervical carcinogenesis should lead to frequent, careful evaluation of HIV
      infected women. Forty-four cervical smears from 23 patients (20 HIV and 3 AIDS)
      were reviewed. While 11 of the 23 patients produced negative smears, 11 had
      abnormal cytological findings on at least one occasion. Sixteen smears (36
      percent) from 10 patients (43%) showed evidence of HPV and/or SIL. Two smears
      (two patients) were assigned to the benign epithelial atypia category. (One of
      these showed keratosis which may indicate HPV infection.) Six smears (three
      patients) represented either a severe Trichomonas, fungal (Candida sp.), or
      Herpes infection. Three smears were deemed unsatisfactory for diagnosis due to
      severe acute inflammation or obscuring blood. Five biopsies were available. In
      four, histologic findings supported the original cytologic diagnosis. One patient
      with a negative smear had a biopsy showing condyloma. This study further supports
      an association of HPV and/or cervical dysplasia with HIV. Careful evaluation and
      follow-up of HIV-infected women is essential.

PMID- 8287758
TI  - Fine-needle aspiration of six carotid body paragangliomas.
AB  - We report six carotid body paragangliomas diagnosed by fine-needle aspiration
      (FNA) in five patients. A total of eight aspirations were performed. The
      cytologic findings are characteristic: hemorrhagic background, hypo- to
      hypercellular smears (depending on the skill of the aspirator) with cells having
      delicate, ill-defined, vacuolated cytoplasm, pleomorphic nuclei with distinct
      nucleoli, rare intranuclear cytoplasmic inclusions, and prominent rosette
      formation. No complications arose in any of the eight aspirations. FNA is a safe,
      accurate means of diagnosing carotid body paragangliomas. It can provide
      essential information for treatment planning and patient management.

PMID- 8287759
TI  - Utility of BER-EP4 in the diagnosis of adenocarcinoma in effusions: an
      immunocytochemical study of 232 cases.
AB  - The usefulness of a new commercially available monoclonal antibody (MoAb) BER-EP4
      was evaluated. This MoAb is directed against a cell surface glycoprotein reported
      to be present in most epithelial cells and epithelial tumors but not in
      mesothelial cells. Cell block sections from 103 adenocarcinomatous and 129 benign
      effusions were studied. Positive staining was seen in 85 of the 103 (83%)
      malignant effusions. Immunoreactivity was seen in 73-93% of adenocarcinomas from
      the ovary, gastrointestinal tract, lung, and breast. Mesothelial cells from 3 of
      the 129 (2%) benign effusions showed positive staining. It is concluded that
      immunocytochemical staining with MoAb BER-EP4 is a sensitive and specific aid in
      distinguishing reactive mesothelial cells from adenocarcinoma cells in body
      fluids.

PMID- 8287760
TI  - Fine-needle aspiration cytology of extramedullary hematopoiesis (myeloid
      metaplasia).
AB  - Myeloproliferative disease may be associated with extramedullary hematopoiesis
      (EH). Clinically, however, the differential diagnosis of solid masses in these
      patients includes not only EH but also inflammatory lesions and malignant
      neoplasms, including granulocytic sarcoma. We report the fine-needle aspiration
      (FNA) cytology of extramedullary hematopoiesis in five patients with a history of
      myeloproliferative disease. All of the masses developed subsequent to the
      diagnosis of myeloproliferative disease. Two of the patients had chronic
      myelogenous leukemia, one had essential thrombocythemia, and two had an
      unspecified chronic myeloproliferative disorder. The patients ranged in age from
      50 to 88 years, and all presented with solid masses involving the kidney (two
      aspirates), liver (one aspirate), and lymph nodes (three aspirates). One of the
      lymph node aspirates was from a paratracheal lymph node. Cytologically, the
      lesions were composed of varying numbers of hematopoietic cells from all three
      hematologic cell lines. The Diff-Quik stain was especially helpful in the
      recognition of the hematopoietic cells such as granulocytic precursors,
      eosinophils, and megakaryocytes. In several cases, the megakaryocytic component
      was particularly prominent. In one case, the Factor VIII immunoperoxidase stain
      was used to confirm the megakaryocytic lineage of the multinucleated cells. The
      cytologic differential diagnosis, which includes granulocytic sarcoma,
      inflammatory disorders, and other lesions containing multinucleated giant cells,
      is discussed.

PMID- 8287761
TI  - Fine-needle aspiration biopsy of Langerhans histiocytosis (histiocytosis-X).
AB  - A series of 14 fine-needle aspiration biopsies (FNAB) from histologically proven
      cases of histiocytosis-x (Hx) were reviewed. The smears revealed a variable
      mixture of Langerhans cells, eosinophils, macrophages, polymorphonuclear cells,
      and giant cells. Based on the predominant cells present, the cases were further
      categorized as Langerhans cell predominant (nine cases), eosinophil predominant
      (two cases), and macrophage predominant (three cases). Langerhans cells were
      usually polygonal without significant evidence of phagocytosis and frequently
      contained indented nuclei. In three cases, several Langerhans cells showed
      prominent dendritic processes. Electron microscopy in 10 cases revealed
      Langerhans cells with varying degrees of morphologic differentiation. All cases
      studied revealed Birbeck granules. These findings indicate that FNAB may be an
      effective technique for diagnosing Hx.

PMID- 8287762
TI  - Negative images due to clofazimine crystals simulating MAI infection in a
      bronchoalveolar lavage specimen.
AB  - "Negative images" of bacilli in mycobacterial infections have been recently
      described in air-dried, Romanovsky-stained cytologic material. We report a case
      of negative images due to crystalline deposition of clofazimine, a drug used to
      treat Mycobacterium avium-intracellulare complex infection in AIDS patients. The
      negative images of clofazimine crystals seen in bronchoalveolar lavage (BAL)
      macrophages resemble the negative images of mycobacterial infection due to the
      pseudogaucher appearance of the cells. Crystals are distinguished by their
      refractile reddish appearance in unfixed, unstained smears, and by their
      birefringence on polarization. Crystals were found in both Pap-stained and Diff
      Quik-stained smears and were negative with Ziehl-Neelsen stains. Clofazimine
      crystals in BAL specimens must be distinguished from the pseudogaucher type cells
      of mycobacterial infection in this patient population. We believe that this is
      the first report of clofazimine crystal deposition diagnosed in a BAL specimen
      along with electron microscopic examination of the cytologic material.

PMID- 8287763
TI  - Solid and papillary epithelial tumour of the pancreas: cytological case study
      with ultrastructural and flow cytometric evaluation.
AB  - An intraoperative cytological diagnosis of a rare solid and papillary epithelial
      tumor of the pancreas was made at laparotomy in a 15-year-old Indian female. The
      characteristic cytological features were the presence of numerous large branching
      papillary clusters with central vascular stalks lined by multiple layers of
      uniform bland cells. Perivascular metachromatic material was prominent on
      Romanovsky stain. Ultrastructural identification of endocrine and exocrine
      features supports a multipotential cell origin in small pancreatic ductules. DNA
      analysis, not previously reported for this tumour, demonstrated a diploid
      population of tumour cells with a low S-phase fraction (0.4%). This would explain
      the bland nuclear morphology and favourable prognosis with a high rate of
      surgical cure for this neoplasm.

PMID- 8287764
TI  - Adenomyoepithelioma of the breast: report of a case initially examined by fine
      needle aspiration.
AB  - This report describes the morphologic features of an adenomyoepithelioma of the
      breast that was first examined by fine-needle aspiration. On retrospective review
      of the cytology, the stromal elements of this adenomyoepithelioma showed
      extensive metachromasia on Diff-Quik stain, had elongated nuclei, and on
      Papanicolaou stain showed elongated, pale, wispy cytoplasm. Clusters of stromal
      cells were usually intimately associated with epithelial elements. While the main
      differential consideration, cystosarcoma phylloides, can show similar features,
      it may be possible to distinguish the two lesions in some instances.

PMID- 8287765
TI  - Fine-needle aspiration biopsy of multiple myeloma in a patient with renal-cell
      carcinoma: a case report.
AB  - A case of multiple myeloma diagnosed by fine-needle aspiration (FNA) biopsy and
      confirmed by laboratory studies in a patient with a history of renal-cell
      carcinoma is presented. The patient was diagnosed with renal-cell carcinoma of
      the right kidney and a radical nephrectomy was performed. Eighteen months after
      this diagnosis was made, the patient developed chest wall pain and was found to
      have osteolytic bone lesions of the ribs and vertebral bodies. FNA of an
      osteolytic rib lesion disclosed multiple myeloma. Additional laboratory studies
      confirmed the diagnosis of multiple myeloma. This case report demonstrates the
      value of FNA as a diagnostic tool for the follow-up of cancer patients, the
      subsequent discrimination between metastatic lesions and a second primary
      malignancy, and the cytology of multiple myeloma.

PMID- 8287766
TI  - Pleomorphic adenoma of the breast: cytology of fine-needle aspiration and its
      differential diagnosis.
AB  - The cytologic findings of a case of pleomorphic adenoma of the breast are
      presented. This rare tumor appeared identical to pleomorphic adenoma of salivary
      glands. It presented diagnostic difficulties, however, because of its rarity and
      the fact that its associated clinical findings suggested a malignancy. The
      cytologic differential diagnosis includes a phyllodes tumor, fibroadenoma, and
      metaplastic carcinoma. Awareness of this entity should permit a definitive
      diagnosis by aspiration biopsy.

PMID- 8287767
TI  - Malakoplakia of the vagina diagnosed by fine-needle aspiration cytology.
AB  - Malakoplakia is an uncommon chronic granulomatous process that most commonly
      affects the urinary tract, but it may rarely recur in the female genital tract.
      It appears to result from a defect in macrophage function resulting in an
      inability to destroy ingested bacteria. We describe the fine needle aspiration
      cytology of malakoplakia in a 84-yr-old woman presenting with a large pelvic mass
      involving the apex of the vagina. The patient's history was significant for
      cervical squamous cell carcinoma in the remote past. CT-guided needle aspiration
      yielded cellular smears with large numbers of isolated histiocytes, as well as
      polymorphonuclear leukocytes, lymphocytes, and plasma cells. The histiocytes had
      central nuclei and abundant granular cytoplasm containing target-shaped,
      laminated bodies (Michaelis-Gutmann bodies). These bodies were PAS positive and
      focally von Kossa positive. Large numbers of intracellular and extracellular
      bacteria were also seen on the smears. The characteristic cytologic findings
      obtained by needle aspiration were diagnostic of malakoplakia with a rare and
      unusual clinical presentation.

PMID- 8287768
TI  - Nodular pulmonary amyloidosis: diagnosis by fine-needle aspiration cytology and a
      review of the literature.
AB  - Solitary nodular pulmonary amyloid tumor is an uncommon benign lesion which is
      seldom diagnosed prior to surgical extirpation. We present a case of unsuspected
      nodular pulmonary amyloid tumor diagnosed by fine needle aspiration cytology. A
      52-yr-old-black woman, presented with a 3-cm right middle lobe mass. Percutaneous
      fine-needle aspiration cytology (FNA) of the mass revealed waxy amorphous
      material that demonstrated apple green birefringence on Congo Red Stain.
      Thoracotomy for diagnosis may be avoided by using FNA to diagnose these unusual
      lesions.

PMID- 8287769
TI  - Renal splenic heterotopia, a rare mimic of renal neoplasia: case report of
      imaging and fine-needle aspiration biopsy.
AB  - Renal splenic heterotopia, a very rare benign occurrence of splenic tissue within
      the renal capsule, mimics organizing capsular hemorrhage, adenomyolipoma and
      renal cortical adenoma or carcinoma. It is found incidentally as a result of
      imaging asymptomatic kidneys for other reasons or may cause signs and symptoms
      due to mass effect and hypersplenism. When occurring in patients who had had
      splenectomy it has been classified as splenosis. When found in patients with
      intact spleens it is called splenorenal fusion and considered to be a
      developmental heterotopia. Renal splenic heterotopia can be diagnosed by 99mTc
      sulfur colloid scan and confirmed with fine needle aspiration biopsy cell block
      preparations. Unnecessary nephrectomy can be avoided if splenic heterotopia is
      included in the differential diagnosis of renal lesions, particularly in
      splenectomized patients.

PMID- 8287770
TI  - Localized primary amyloid tumor associated with osseous metaplasia presenting as
      bilateral breast masses: cytologic and radiologic features.
AB  - This report details the cytologic features of primary localized amyloid tumor of
      the breast presenting as bilateral breast masses in a 72-yr-old woman. Clinically
      and radiographically, the masses simulated metastatic or multifocal carcinoma.
      Fine-needle aspiration revealed irregular globules of acellular amorphous
      material and numerous multinucleated giant cells resembling granulomatous
      inflammation. Histology confirmed amyloid tumors with a foreign-body giant cell
      reaction in response to amyloid and foci of osseous metaplasia. Subsequent
      clinical workup included a serum electrophoresis and immunofixation which showed
      a small IgG kappa monoclonal protein. Urine immunofixation was negative for Bence
      Jones protein. Bone marrow examination revealed no evidence of a plasma cell
      dyscrasia. To date the patient has not developed clinical or laboratory evidence
      of systemic amyloidosis or multiple myeloma. Amyloidosis involving the breast and
      specifically localized primary amyloid tumors of the breast are rare and
      infrequently reported entities. To our knowledge, osseous metaplasia within
      isolated primary amyloid tumors of the breast has not been reported. We present
      this unusual case to illustrate the intratumoral calcification patterns mimicking
      carcinoma and to characterize the cytologic features. Emphasis is placed on the
      inclusion of amyloidosis in the differential diagnosis of breast masses.

PMID- 8287771
TI  - Fine-needle aspiration of cutaneous malakoplakia.
AB  - A 99-yr-old Chinese woman with cutaneous malakoplakia and concomitant urinary
      tract infection was reported. The patient presented with an ulcerated right lower
      quadrant mass and computerized tomography showed that it was limited to the skin
      and subcutaneous tissue with no extension to the pelvic or abdominal structures.
      The patient also suffered from urinary tract infection and was treated with oral
      norfloxacin. The ulcerated subcutaneous mass disappeared on follow-up visit 6
      months after presentation. The cytologic (fine-needle aspiration), histologic
      (trucut biopsy) and ultrastructural features of cutaneous malakoplakia were
      described. The possible usefulness of fine-needle aspiration in the diagnosis of
      this condition was discussed.

PMID- 8287772
TI  - "Cellular adenomatoid nodules" of the thyroid: review of 219 fine-needle
      aspirates.
AB  - We reviewed 219 consecutive thyroid aspirates previously diagnosed as "cellular
      adenomatoid nodule," applying the criteria presented in this paper and
      reclassifying them as 146 adenomatoid nodules (AN), 31 cellular adenomatoid
      nodules (CELL-AN), 29 cellular adenomatoid nodules vs. follicular neoplasms (CELL
      AN vs. FN), 5 follicular neoplasms (FN), 2 FN of oxyphilic cell type, 4 papillary
      carcinomas, and 2 chronic lymphocytic (Hashimoto's) thyroiditis. Of the 146
      adenomatoid nodules, 14 occurred in multinodular goiters on histologic
      examination. Of the 31 CELL-AN, five had surgery: two were follicular adenomas,
      one was papillary carcinoma, and two were multinodular goiters. Of the 29 CELL-AN
      vs. FN, 11 had surgery: six were follicular adenomas, two were follicular
      carcinomas, two were multinodular goiters, and one was Hashimoto's thyroiditis.
      Surgery on four FN showed follicular adenomas (a fifth patient was lost to follow
      up). Of the two FN of oxyphilic cell type, one was a multinodular goiter and the
      other a follicular adenoma with oxyphilic cells. Three of the four papillary
      carcinomas were confirmed histologically (one patient was lost to follow-up). Of
      the two cases showing Hashimoto's thyroiditis, one was diagnosed as FN on repeat
      aspiration and follicular carcinoma at surgery. After review, we identified 40
      patients at higher risk of harboring a neoplasm and 31 with cellular adenomatoid
      nodules. Twenty-five underwent surgery with the above results. In the
      classification of follicular lesions of the thyroid by FNA, adherence to strict
      cytologic criteria helps identify those patients who will benefit most from
      surgery.

PMID- 8287773
TI  - Evaluation of a method for cryogenic storage of cytological specimens.
AB  - A technique for long-term storage of cytological specimens at -70 degrees C was
      evaluated with a range of nongynaecological cytology specimens. The effects of
      frozen storage on the cellularity, morphology, ultrastructure, and reactivity to
      cytochemical and immunochemical stains were investigated. These parameters were
      compared in preparations made from specimens processed conventionally and after
      frozen storage. No significant deterioration in the quality of subsequent
      preparations was apparent after storage. The method is technically simple and has
      proven successful for storing a range of specimens, including serous effusions,
      urine samples, and fine-needle aspirates. This technique allows storage of
      material until initial microscopic evaluation is complete. If required, the
      relevant adjuvant procedure, such as cell blocking, may then be carried out using
      the stored material. Wastage of cytological material on unnecessary preparations
      is minimised, and material may be stored over years for research or confirmation
      procedures.

PMID- 8287774
TI  - Classics in cytology. VI: The early cytologic discoveries of Lionel S. Beale.

PMID- 8287775
TI  - Bizarre spindle cells in urine cytology specimens.

PMID- 8287776
TI  - Liesegang rings in an aspirate from a breast abscess.

PMID- 8287777
TI  - [Minimal heparinization in dialysis patients with increased risk of bleeding].
AB  - In 78 patients (47 men, 31 women; mean age 53 [22-78] years) 174 dialyses were
      undertaken within one week of a bleeding episode or a diagnostic or therapeutic
      procedure which may cause bleeding. Minimal anticoagulation with low molecular
      weight heparin (LMWH) was the aim, using a biocompatible dialyser. During the
      dialysis coagulation was controlled by global tests (Quick value/international
      normalized ratio [INR], partial thromboplastin time, thrombin time, antifactor Xa
      activity), by molecular markers of clotting activity (thrombin-antithrombin III
      complex [TAT], D-dimers), as well as measurement of elastase (elastase-alpha 1
      protein inhibitor complex). The LMWH dosage averaged 932 units as an initial
      bolus and 234 units/h as a continuous infusion. In the group of chronic dialysis
      patients (n = 72) this meant (standard heparin units = 2/3 LMWH units) a
      reduction to 45 +/- 11% from the previously used routine heparin dosage for a 4
      hour dialysis. All dialyses were completed without bleeding complications.
      Considerable clotting formation in the extracorporeal circulation occurred in 11
      dialyses (6.3%). TAT, D-dimer and elastase values proved to be suitable for
      determining individual clotting activity and for reducing anticoagulation to the
      minimum.

PMID- 8287778
TI  - [Central sleep apnea syndrome as a cause of impaired wakefulness in multiple
      myeloma].
AB  - Progressive day-time sleepiness developed in a 73-year-old man for 3 years known
      to have kappa-light-chain myeloma, treated with radio- and chemotherapy. His
      powers of concentration and intellectual performance were diminished. Neither
      clinical nor biochemically was there any indication of abnormal water and
      electrolyte metabolism or hyperviscosity syndrome. The neurological examination
      was unremarkable. His wife's observation of nocturnal breathing pauses suggested
      sleep-related abnormal breathing. Polysomnography showed severe central sleep
      apnoea: an apnoea index of 60/h and blood oxygen saturations as low as 78%. On
      biphasic positive airway pressure (BIPAP) ventilation by nasal mask at night the
      apnoea index fell to 6/h and the symptoms improved. During a break in treatment
      the day-time sleepiness again increased and regressed once again with BIPAP
      ventilation. There is a 1-5% prevalence of sleep-related impaired breathing among
      adults. This condition should thus be considered in the differential diagnosis of
      characteristic day-time sleepiness.

PMID- 8287779
TI  - [Reproducible ventricular flutter during programming of a DDD pacemaker].
AB  - A bipolar DDD pacemaker system was implanted in a 51-year-old woman with a 2
      degrees (Mobitz type) atrioventricular block. The first postimplantation control
      was unremarkable, but she collapsed 9 weeks later with dyspnoea, tachycardia and
      profound perspiration. Ventricular flutter occurred twice during routine
      ambulatory pacemaker function tests one week later. The first episode was
      terminated by a precordial blow with a fist, but the second required electrical
      defibrillation. During the subsequent hospitalization abnormal electrolyte
      balance and digitalis intoxication were excluded. Left-heart catheterization with
      coronary angiography showed normal left-ventricular function at rest and normal
      coronary arteries. There was no evidence for an arrhythmogenic right ventricle.
      Electrophysiological testing with programmed ventricular stimulation provoked
      ventricular tachycardia with torsade de pointes and transition to ventricular
      fibrillation. Antiarrhythmic treatment with sotalol, 160 mg twice daily by mouth,
      failed to suppress the episodes of torsade de pointes. But further programmed
      ventricular stimulation was uneventful after the sotalol dosage had been
      increased to 160 mg three times daily.

PMID- 8287780
TI  - [Chloroquine retinopathy: avoidable by individualized daily dosing].

PMID- 8287781
TI  - [Captopril].

PMID- 8287782
TI  - [Cytokines and infections. Pathogenetic and therapeutic aspects].

PMID- 8287783
TI  - [Forced feeding in geriatric care].

PMID- 8287784
TI  - [Palmoplantar hyperhidrosis].

PMID- 8287785
TI  - [Tolerance and pseudo-tolerance following administration of nitrates].

PMID- 8287786
TI  - [Cerebral spasm during malaria prophylaxis with mefloquine].

PMID- 8287787
TI  - [Adrenal gland hemorrhage as cause of acute abdominal symptoms].

PMID- 8287788
TI  - [Pulmonary angiodysplasia with fatal lung hemorrhage].

PMID- 8287789
TI  - [Chemotherapy in therapy-refractive immunothrombocytopenic purpura].

PMID- 8287790
TI  - Novel genes expressed differentially in ascidians with alternate modes of
      development.
AB  - We have used a subtractive procedure to isolate cDNA clones encoding genes
      expressed differentially in ascidian species with alternate modes of development.
      The ascidians used in this study were Molgula occulta, which develops a tailed
      (urodele) larva, and Molgula occulta, which develops a tailless (anural) larva.
      Two of the identified clones, Uro-2 and Uro-11, are described. Southern blots
      show that the Uro-2 and Uro-11 genes are present in both species, but the
      corresponding mRNAs are expressed preferentially in the urodele species. In situ
      hybridization showed that Uro-2 and Uro-11 transcripts accumulate in small
      oocytes during oogenesis. The maternal Uro-2 and Uro-11 transcripts were
      distributed throughout the oocyte cytoplasm. Transcript concentrations declined
      during vitellogenesis, but mature eggs still contain detectable levels of Uro-2
      and Uro-11 mRNA. After fertilization, the maternal Uro-2 and Uro-11 transcripts
      were localized in the ectoplasm of uncleaved zygotes and mostly entered the
      ectoderm cells during cleavage. The Uro-2 gene appears to produce only maternal
      transcripts. In contrast, the Uro-11 gene may also produce zygotic transcripts,
      which accumulate between gastrulation and neurulation in posterior epidermis,
      neural and tail muscle cells. Zygotic expression of the Uro-11 gene was not
      detected in embryos of the anural species. The deduced amino acid sequences of
      the Uro-2 and Uro-11 cDNAs suggest that they encode novel basic proteins with
      distinctive structural features. The predicted Uro-2 protein contain, a leucine
      zipper motif, suggesting that it may dimerize with another protein. The predicted
      Uro-11 protein contains a nuclear localization signal, a region with similarity
      to part of the DNA-binding motif in the bacterial histone-like HU and IHF
      proteins, 12 repeats of the proposed DNA-binding motif S(T)PXX, and a potential
      zinc finger of the C6 or C6H2 class, suggesting that it may be a DNA-binding
      protein. The Uro-2 and Uro-11 proteins are candidates for regulatory factors
      involved in the evolutionary transition from urodele to anural development.

PMID- 8287791
TI  - Two rhombomeres are altered in Hoxa-1 mutant mice.
AB  - This study provides a detailed description of the anatomical defects in the Hoxa
      1-/- mutant mice previously generated in our laboratory (T. Lufkin, A. Dierich,
      M. LeMeur, M. Mark and P. Chambon, 1991; Cell 66, 1105-1119). Three-dimensional
      reconstructions of the Hoxa-1-/- rhombencephalon reveals that it bears only five
      rhombomeric structures (ie. morphological segments) instead of the normal seven.
      The first three of these rhombomeres appear normal as judged from the
      distribution pattern of CRABPI transcripts in the neurectoderm and from the
      histological analysis of the cranial nerve components derived from these
      structures. In contrast, the neural-crest-cell-free region normally located
      opposite rhombomere 5 is lacking in Hoxa-1-/- embryos, and motor neurons of the
      facial and abducens nerves, which normally differentiate within rhombomeres 4, 5
      and 6, are missing in Hoxa-1-/- fetuses. These morphological data, combined with
      the determination of the molecular positional identities of the rhombomeres 4 and
      5 (P. Dolle, T. Lufkin, R. Krumlauf, M. Mark, D. Duboule and P. Chambon, 1993;
      Proc. Natl. Acad. Sci. USA, in press), suggest that rhombomere 4 is markedly
      reduced, whereas rhombomere 5 is almost absent. Thus, the remnants of rhombomeres
      4 and 5 appear to be fused caudally with rhombomere 6 to form a single fourth
      rhombomeric structure. Moreover, the migration of neural crest cells contributing
      to the glossopharyngeal and vagus nerves occurs in a more rostral position,
      resulting in abnormalities of these cranial nerves, which were visualized by
      whole-mount anti-neurofilament immunostaining. The mutual relationship along the
      rostrocaudal axis between the otic pit and the neuroepithelial site of int-2
      protein secretion (a putative otogenic cue) is not significantly changed in Hoxa
      1-/- embryos. However, the abnormal relationship between the rhombencephalon and
      the epithelial inner ear may account for the aplasia and faulty differentiation
      of the membranous labyrinth, the disruption of the cartilaginous otic capsule and
      the disorganisation of some middle ear structures. This phenotype is compared
      with that of the Hoxa-1-/- mutants generated by O. Chisaka, T. S. Musci and M. R.
      Capecchi, 1992 (Nature 335, 516-520) and with that of the mice homozygous for the
      kreisler mutation.

PMID- 8287792
TI  - Heterogeneity in the expression of fibroblast growth factor receptors during limb
      regeneration in newts (Notophthalmus viridescens).
AB  - Two closely related fibroblast growth factor receptors, FGFR1 and FGFR2, have
      been cloned from a newt (Notophthalmus viridescens) limb blastema cDNA library.
      Sequence analysis revealed that we have isolated both the bek and KGFR variants
      of FGFR2. These two variants differ only in the second half of the last of their
      three Ig-like domains. The expression patterns of FGFR1 and FGFR2 during limb
      regeneration have been determined by in situ hybridization. During the
      preblastema stages of regeneration, FGFR2 expression is observed in the basal
      layer of the wound epithelium and in the cells of the periosteum. As regeneration
      progresses to the blastema stages, FGFR2 expression continues to be observed in
      the basal layer of the wound epithelium with additional hybridization seen in the
      blastema mesenchyme closely associated with the bisected bones. From the early
      bud to the mid-bud blastema stage, FGFR1 expression is observed throughout the
      blastema mesenchyme but, unlike FGFR2, is distinctly absent from the wound
      epithelium. In the differentiation stages of regeneration, the mesenchymal
      expression of FGFR2 becomes restricted to the cells of the condensing cartilage
      and later to the perichondrium. During these later stages of regeneration, the
      wound epithelium hybridization to the FGFR2 probe is no longer observed. The
      expression patterns of these receptors suggest that FGFR1 and FGFR2 have distinct
      roles in limb regeneration, despite their sharing a number of the FGF ligands.
      Further investigation regarding the potential sources of the FGF ligands will
      help establish the role that FGFs and FGFRs play in limb regeneration.

PMID- 8287793
TI  - Defective lens fiber differentiation and pancreatic tumorigenesis caused by
      ectopic expression of the cellular retinoic acid-binding protein I.
AB  - All-trans retinoic acid, a metabolite of retinol, is a possible morphogen in
      vertebrate development. Two classes of cellular proteins, which specifically bind
      all-trans retinoic acid, are thought to mediate its action: the nuclear retinoic
      acid receptors (RAR alpha, beta, gamma), and the cytoplasmic binding proteins
      known as cellular retinoic acid-binding proteins I and II (CRABP I and II). The
      function of the retinoic acid receptors is to regulate gene transcription by
      binding to DNA in conjunction with the nuclear retinoid X receptors (RXR alpha,
      beta, gamma), which in turn have 9-cis retinoic acid as a ligand. Several lines
      of evidence suggest that the role of the cellular retinoic acid-binding proteins
      is to control the concentration of free retinoic acid reaching the nucleus in a
      given cell. Here, we have addressed the role of the cellular retinoic acid
      binding protein I in development by ectopically expressing it in the mouse lens,
      under the control of the alpha A-crystallin promoter. We show that this ectopic
      expression interferes with the development of the lens and with the
      differentiation of the secondary lens fiber cells, causing cataract formation.
      These results suggest that correct regulation of intracellular retinoic acid
      concentration is required for normal eye development. In addition, the generated
      transgenic mice also present expression of the transgene in the pancreas and
      develop pancreatic carcinomas, suggesting that overexpression of the cellular
      retinoic acid-binding protein is the cause of the tumors. These results taken
      together provide evidence for a role of the cellular retinoic acid-binding
      protein in development and cell differentiation. The relevance of these findings
      to the possible role of the cellular retinoic acid-binding proteins in the
      transduction of the retinoic acid signal is discussed.

PMID- 8287794
TI  - The strawberry notch gene functions with Notch in common developmental pathways.
AB  - Genetic and phenotypic analysis of strawberry notch suggests that its gene
      product is required during embryogenesis and oogenesis, and for the development
      of the eye, wing and leg. Several lines of evidence suggest that strawberry notch
      participates together with Notch in many common pathways. A number of strawberry
      notch mutant phenotypes are similar to those of Notch mutants and can be rescued
      by an extra copy of wild-type Notch. In addition, mutations in strawberry notch
      interact strongly with Notch mutants in a tissue-specific manner. Mutations in
      the strawberry notch and Notch loci also show very similar interactions with
      genes like Hairless, Delta, groucho, Serrate, and deltex that have all been
      proposed to participate in Notch related pathways. The genetic evidence presented
      here suggests that strawberry notch participates with members of the Notch
      pathway in facilitating developmentally relevant cell-cell communications.

PMID- 8287795
TI  - CLAVATA1, a regulator of meristem and flower development in Arabidopsis.
AB  - We have investigated the effects on plant development of mutations in the
      Arabidopsis thaliana CLAVATA1 gene. In clavata1 plants, vegetative, inflorescence
      and floral meristems are all enlarged relative to wild type. The apical meristem
      can fasciate in the more severe mutant alleles, and this fasciation can occur
      prior to the transition to flowering. Flowers of clavata1 plants can have
      increased numbers of organs in all four whorls, and can also have additional
      whorls not present in wild-type flowers. Double mutant combinations of clavata1
      with agamous, apetala2, apetala3 and pistillata indicate that CLAVATA1 controls
      the underlying floral meristem structure upon which these homeotic genes act.
      Double mutant combinations of clavata1 with apetala1 and leafy indicate CLAVATA1
      plays a role in establishing and maintaining floral meristem identity, in
      addition to its role in controlling meristem size. In support of this, RNA
      expression patterns of AGAMOUS and APETALA1 are altered in clavata1 flowers.

PMID- 8287796
TI  - The zebrafish midblastula transition.
AB  - The zebrafish midblastula transition (MBT) begins at cycle 10. It is
      characterized by cell cycle lengthening, loss of cell synchrony, activation of
      transcription and appearance of cell motility. Superceding a 15 minute oscillator
      that controls the first nine cycles, the nucleocytoplasmic ratio appears to
      govern the MBT. This timing mechanism operates cell autonomously: clones of
      labeled cells initiate cell cycle lengthening independently of neighbors but
      dependent on immediate lineal ancestors. Unequal divisions, when they occur,
      produce asymmetric cell cycle lengthening based on the volume of each daughter.
      During the several cycles after the MBT begins, cycle length is correlated with
      the reciprocal of the blastomere volume, suggesting a continuation of cell cycle
      regulation by the nucleocytoplasmic ratio during an interval that we term the
      'MBT period'.

PMID- 8287797
TI  - Relationship between expression of serendipity alpha and cellularisation of the
      Drosophila embryo as revealed by interspecific transformation.
AB  - A dramatic reorganization of the cytoskeleton underlies the cellularisation of
      the syncytial Drosophila embryo. Formation of a regular network of acto-myosin
      filaments, providing a structural framework, and possibly a contractile force as
      well, appears essential for the synchronous invagination of the plasma membrane
      between adjacent nuclei. The serendipity alpha (sry alpha) gene is required for
      this complete reorganization of the microfilaments at the onset of membrane
      invagination. We compare here the structure and expression of sry alpha between
      D. pseudoobscura, D. subobscura and D. melanogaster. Interspersion of
      evolutionarily highly conserved and divergent regions is observed in the protein.
      One such highly conserved region shows sequence similarities to a motif found in
      proteins of the ezrin-radixin-moesin (ERM) family. Four 7-13 bp motifs are
      conserved in the 5' promoter region; two of these are also found, and at the same
      position relative to the TATA box, in nullo, another zygotic gene recently shown
      to be involved in cellularisation. The compared patterns of expression of D.
      melanogaster sry alpha and nullo, and D. pseudoobscura sry alpha reveal a complex
      regulation of the spatiotemporal accumulation of their transcripts. The D.
      pseudoobscura sry alpha gene is able to rescue the cellularisation defects
      associated with a complete loss of sry alpha function in D. melanogaster embryos,
      even though species-specific aspects of its expression are maintained. Despite
      their functional homologies, the D. melanogaster and D. pseudoobscura sry alpha
      RNAs have different subcellular localisations, suggesting that this specific
      localization has no conserved role in targeting the sry alpha protein to the
      apical membranes.

PMID- 8287798
TI  - Defects in heart and lung development in compound heterozygotes for two different
      targeted mutations at the N-myc locus.
AB  - Two types of mutant allele, one leaky and one null, have been generated by gene
      targeting at the N-myc locus in embryonic stem cells and the phenotypes of mice
      homozygous for these mutations have been described. These mutations have shown
      that N-myc has a number of functions during development, including a role in
      branching morphogenesis in the lung, which manifests itself at birth in mice
      homozygous for the leaky allele, and roles in the development of the mesonephric
      tubules, the neuroepithelium, the sensory ganglia, the gut and the heart, which
      become evident at midgestation in embryos homozygous for the null allele. In an
      attempt to define roles for N-myc at other stages of development, we have
      combined the two types of N-myc mutant allele in a compound heterozygote that as
      a result contains approximately 15% of normal levels of N-Myc protein. Compound
      heterozygotes died during gestation at a time intermediate to the times of death
      of embryos homozygous for either mutation individually, and their death appeared
      to result from cardiac failure stemming from hypoplasia of the compact
      subepicardial layer of the myocardium. Investigation of the expression pattern of
      N-myc and various markers of differentiation in wild-type and compound
      heterozygote mutant hearts has suggested that N-myc may function in maintaining
      the proliferation and/or preventing the differentiation of compact layer
      myocytes. This study illustrates the importance of generating different mutations
      at a given locus to elucidate fully the function of a particular gene during
      development.

PMID- 8287799
TI  - Segment polarity gene interactions modulate epidermal patterning in Drosophila
      embryos.
AB  - Each segment of a Drosophila larva shows a precisely organized pattern of
      cuticular structures, indicating diverse cellular identities in the underlying
      epidermis. Mutations in the segment polarity genes alter the cuticle pattern
      secreted by the epidermal cells; these mutant patterns provide clues about the
      role that each gene product plays in the development of wild-type epidermal
      pattern. We have analyzed embryos that are multiply mutant for five key
      patterning genes: wingless, patched, engrailed, naked and hedgehog. Our results
      indicate that wild-type activity of these five segment polarity genes can account
      for most of the ventral pattern elements and that their gene products interact
      extensively to specify the diverse cellular identities within the epidermis. Two
      pattern elements can be correlated with individual gene action: wingless is
      required for formation of naked cuticle and engrailed is required for formation
      of the first row of denticles in each abdominal denticle belt. The remaining cell
      types can be produced by different combinations of the five gene activities.
      wingless activity generates the diversity of cell types within the segment, but
      each specific cell identity depends on the activity of patched, engrailed, naked
      and hedgehog. These molecules modulate the distribution and interpretation of
      wingless signalling activity in the ventral epidermal cells and, in addition,
      each can contribute to pattern through a pathway independent of the wingless
      signalling pathway.

PMID- 8287800
TI  - Expression of the chicken GATA factor family during early erythroid development
      and differentiation.
AB  - The DNA motif WGATAR has been identified within transcriptional regulatory
      domains of globin and other erythroid-specific genes and the activator proteins
      that bind to this regulatory element, the GATA factors, belong to a multi-gene
      family that is expressed in chicken erythroid cells. Here we show that, as in
      chickens, multiple members of the GATA factor family are expressed in human and
      murine erythroid cells. During the early stages of chicken embryogenesis (well
      before blood island formation), each of the GATA family members is transcribed
      with a unique temporal and spatial pattern. In the primitive erythroid lineage,
      transcription of the embryonic epsilon-globin gene parallels GATA-1 expression
      while the switch to beta-globin transcription in definitive erythroid cells is
      directly preceded by a pronounced increase in GATA-3 accumulation. The timing and
      pattern of expression of these different mRNAs during avian erythroid development
      and differentiation suggests that temporally regulated changes in GATA factor
      expression are required for vertebrate hematopoiesis.

PMID- 8287801
TI  - Muscle development is independent of innervation during Drosophila embryogenesis.
AB  - We have examined the role of innervation in directing embryonic myogenesis, using
      a mutant (prospero), which delays the pioneering of peripheral motor nerves of
      the Drosophila embryo. In the absence of motor nerves, myoblasts fuse normally to
      form syncytial myotubes, myotubes form normal attachments to the epidermis, and a
      larval musculature comparable to the wild-type pattern is generated and
      maintained. Likewise, the twist-expressing myoblasts that prefigure the adult
      musculature segregate normally in the absence of motor nerves, migrate to their
      final embryonic positions and continue to express twist until the end of
      embryonic development. In the absence of motor nerves, myotubes uncouple at the
      correct developmental stage to form single cells. Subsequently, uninnervated
      myotubes develop the mature electrical and contractile properties of larval
      muscles with a time course indistinguishable from normally innervated myotubes.
      We conclude that innervation plays no role in the patterning, morphogenesis,
      maintenance or physiological development of the somatic muscles in the Drosophila
      embryo.

PMID- 8287802
TI  - Expression and binding characteristics of the BDNF receptor chick trkB.
AB  - Previous studies using transfected cells have indicated that the mammalian
      receptor tyrosine kinase trkB binds the neurotrophins brain-derived neurotrophic
      factor, neurotrophin-3 and neurotrophin-4. However, most studies demonstrating
      that these neurotrophins prevent the death of embryonic neurons and have specific
      neuronal receptors have been performed with chick neurons. In order to explore
      the possibility that trkB is the molecular entity representing the high-affinity
      receptor for brain-derived neurotrophic factor on embryonic chick neurons, we
      cloned and expressed a chick trkB cDNA. In situ hybridisation results indicate
      that the distribution of trkB mRNA in the peripheral nervous system of the
      developing chick embryo correlates well with the structures known to respond to
      brain-derived neurotrophic factor. Binding studies performed with a cell line
      stably transfected with the ctrkB cDNA indicate a dissociation constant for brain
      derived neurotrophic factor of 9.9 x 10(-10) M, which is distinctly higher than
      that found on primary chick sensory neurons (1.5 x 10(-11) M). When binding of
      brain-derived neurotrophic factor was determined in the presence of other
      neurotrophins, neurotrophin-3 was found efficiently to prevent the binding of
      brain-derived neurotrophic factor to both the ctrkB cell line and embryonic
      sensory neurons. In vitro, neurotrophin-3 at high concentrations completely
      blocked the survival normally seen with brain-derived neurotrophic factor. Thus,
      unlike previous cases of receptor occupancy by heterologous neurotrophins (which
      resulted in agonistic effects), the interaction between the brain-derived
      neurotrophic factor receptor and neurotrophin-3 on sensory neurons is
      antagonistic.

PMID- 8287803
TI  - Regulation of extracellular fluid volume in neonates.
AB  - This review summarises mechanisms of control of extracellular fluid volume in the
      neonatal period. 'Normal' body fluid distribution and methods of its measurement
      are discussed as well as regulatory mechanisms with particular emphasis on
      hormonal and renal aspects.

PMID- 8287804
TI  - In-situ pulmonary vascular morphology and lung volume in the fetal and neonatal
      rat.
AB  - In situ cross-sectional morphology of the pulmonary arteries, veins, and lung
      volumes were studied following rapid whole-body freezing of the fetal and
      neonatal rat. In the fetus, the right and left main pulmonary arteries were much
      smaller than the pulmonary trunk, and the ratio of the internal diameter of the
      right or the left pulmonary artery to the diameter of the pulmonary trunk was
      0.44 and 0.38, respectively. One day after birth, the right and the left main
      pulmonary arteries enlarged, and the ratio of the right pulmonary artery to the
      pulmonary trunk increased to 0.82. The proximal right and left pulmonary arteries
      immediately adjacent to the bifurcation enlarged slowly, and showed diffuse
      narrowing at the proximal portions adjacent to the bifurcation. The narrowing
      disappeared 3 and 4 days after birth as the proximal pulmonary artery enlarged
      and the ratio of the right pulmonary artery to the pulmonary trunk reached 0.8.
      The pulmonary vein showed rapid enlargement in these neonates, concordant with
      the enlargement of the pulmonary arteries. Lung volume increased to 131% of the
      fetal volume 10 min after caesarean section. These studies quantitated neonatal
      pulmonary vascular adaptation. Delayed enlargement of the pulmonary arteries
      adjacent to the bifurcation in the neonatal period was shown, and presented a
      morphologic basis for the physiologic gradient and transient systolic murmur in
      the pulmonary arteries in human neonates.

PMID- 8287805
TI  - Cerebral hyperperfusion following episodes of bradycardia in the preterm infant.
AB  - The alterations in cerebral hemodynamics during and following 39 episodes with
      bradycardia of different severity have been studied by analysis of Doppler flow
      velocity waveforms amongst 16 stable preterm infants (range of conceptional age
      at the time of study 33-39 weeks; weight 1730-2820 g). Each episode with
      bradycardia has been classified as mild on seven occasions (heart rate between
      100-120 beats/min), moderate on 15 occasions (80-100), or severe on 17 occasions
      (heart rate below 80) Depending on the severity of the bradycardia, the time
      averaged mean flow velocity (V) could decrease by 80% below the preexistent
      baseline value and the end-diastolic velocity (D) dropped towards the zero line,
      whereas peak systolic velocities did not change The magnitude of the percentage
      decrease of V correlated positively with the severity of bradycardia, indicating
      a progressive decline of cerebral blood flow (CBF). Following bradycardia, V
      could increase up to 75% above the preexistent baseline value. Simultaneously, an
      increase of mean arterial blood pressure and D could be documented. Peak systolic
      velocities remained unaltered. The magnitude of the percentage increase of V
      following bradycardia depended both on the severity of bradycardia as well as on
      the drop in transcutaneous oxygen during the preceding bradycardia.
      Interpretation of these findings suggested that the transient cerebral
      hyperperfusion following bradycardia compensates for the hypoxic-ischemic
      episode, sustained during the preceding epoch of apnea and bradycardia.

PMID- 8287806
TI  - Association of abnormal flow velocity waveforms in the uterine artery with
      frequency-specific fetal heart rate variability.
AB  - The aim of the study was to determine if abnormal flow velocity waveforms in the
      uterine artery are associated with altered frequency-specific fetal heart rate
      variability (HRV). Fetuses in the last third of gestation were studied. In seven
      fetuses the pulsatility index (PI) of the blood flow velocity waveform in the
      uterine artery was increased (Group II), and in ten fetuses the PI was normal
      (Group I). Frequency-specific HRV (0.025-0.07 Hz, 0.07-0.13 Hz, 0.13-1.0 Hz) was
      quantified by power spectral analysis and correlated with the PI in the uterine
      artery, umbilical artery and the middle cerebral artery. The slow variability
      dominated the fetal HRV. There was no difference between the groups in the mean
      frequency-specific variability. In Group II, an increase of the PI in the
      umbilical artery and a decrease in the middle cerebral artery correlated with an
      increase of HRV, the increase being greatest at the lowest frequency band.

PMID- 8287807
TI  - Arterial blood pressure and blood flow velocity in major cerebral and visceral
      arteries. I. Interindividual differences.
AB  - In order to determine the relationship between blood pressure and arterial blood
      flow velocity in various regional circulations, Doppler ultrasound measurements
      of blood flow velocity were recorded on the first day of postnatal life from the
      anterior cerebral (ACA), superior mesenteric, coeliac axis and left renal artery.
      In 34 ventilated very low birth weight (VLBW) infants, results were correlated
      with arterial blood pressure and blood gases in a multiple regression model. ACA
      velocity was correlated with blood pressure (r = 0.70) and PaCO2 (r = 0.64), but
      there was no relationship between blood pressure and velocity in the other
      arteries. Repeated measurements were performed at one week of age in 15 infants.
      Blood flow velocity in the cerebral and renal arteries was related to blood
      pressure; velocity in the cerebral arteries was inversely correlated with PaO2
      and velocity in the coeliac and mesenteric arteries was positively correlated
      with PaO2. In VLBW infants on the first day of life, blood flow velocity is
      related to blood pressure in the cerebral circulation only.

PMID- 8287809
TI  - Endoscopic ultrasonography in the local staging of primary gastric lymphoma.
AB  - Endoscopic ultrasonography (EUS) and endoscopy were prospectively performed and
      compared to the histopathologic findings of the resection specimens in 24
      patients with primary gastric lymphoma (PGL). On EUS, three types of PGL could be
      differentiated, a superficial type (n = 10), an infiltrating type (n = 12) and a
      tumorous type (n = 2). In the correct assessment of surface extension of the
      tumors, endoscopy and EUS agreed in 37.5% of cases and EUS showed more extensive
      disease than endoscopy in 58% of cases. However, in comparison to the resection
      specimens, EUS still underestimated the tumor surface extension in 37.5% of
      cases; this was mainly in low grade malignant PGL. The depth of tumor
      infiltration was correctly determined on EUS compared to the resection specimens
      in 91.5% of cases. Sensitivity, specificity and accuracy of diagnosing lymph node
      metastases were 100%, 80% and 83%, respectively. We conclude that EUS is a useful
      pre-therapeutic staging tool for primary gastric lymphoma but there remain some
      problems in determining the longitudinal and circular tumor spread in order to
      accurately guide the extent of gastric resection.

PMID- 8287808
TI  - Endoscopic and bioptic diagnosis of malignant non-Hodgkin's lymphoma of the
      stomach.
AB  - Experience in the endoscopic and bioptic diagnosis of malignant non-Hodgkin's
      lymphomas of the stomach in 66 patients is reported all of which were B cell
      lymphomas originating in the mucosa associated lymphoid tissue (MALT) type. Two
      types of tumor could be differentiated by their appearance on endoscopy (two
      patients had both types). An exophytic type (n = 24) was easily recognized as
      malignancy on endoscopy and the diagnosis confirmed by endoscopic biopsy (mean of
      1.2 endoscopic-bioptic examinations). It could be classified according to the
      Palmer classification; 50% were low-grade malignancies and 50% high-grade
      malignancies. Resection (n = 17) showed wall penetration beyond the muscularis
      propria in 70%. An infiltrative type (n = 44) was difficult to diagnose by means
      of endoscopy and biopsy (mean of 2.9 endoscopic-bioptic examinations); in one
      case a histological diagnosis could only be established on surgery. A
      classification system is suggested for this type (I--elevated, II--flat, III-
      cavitated). Most of these lymphomas were low-grade malignancies (77%), and
      limited to the mucosa and submucosa (79% of 34 resected cases). It is concluded
      that attention should be paid especially to the infiltrative type of gastric
      lymphoma which is difficult to diagnose and to differentiate from other gastric
      conditions such as ulcers and erosions, but which is most often found at an early
      stage and has a better prognosis. Complete tumor resection (R0) was achieved in
      49 of 51 patients undergoing surgery (96%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287810
TI  - Role of endosonography in the surgical management of non-Hodgkin's lymphoma of
      the stomach.
AB  - Ten patients with primary gastric non-Hodgkin's lymphoma (NHL) were
      preoperatively assessed by endoscopic ultrasonography (EUS). Tumor infiltration
      depth and lymph node involvement were assessed using the TNM classification
      system. EUS was 80% accurate in determining the TL stage and 90% in detecting
      lymph node metastases (NL stage). Based on the longitudinal tumor extent (antrum
      to fundus), as assessed by preoperative (n = 10) and additionally, intraoperative
      EUS (n = 3), partial gastric resection was performed in nine patients and total
      gastrectomy in one. All resection specimens had tumor-free resection margins (R0
      resection rate 100%). These results were compared to those in 23 patients with
      gastric NHL operated on prior to the introduction of EUS in the hospital who were
      comparable with respect to tumor location and extent. In comparison with the ten
      cases where treatment was guided by EUS, the rate of total gastrectomy was higher
      (65% versus 10%) and the R0 resection rate lower (72% versus 100%) in this group
      of 23 patients. These results show that EUS may play a crucial role in the pre
      surgical staging of gastric NHL.

PMID- 8287811
TI  - A double-blind randomized controlled trial comparing sodium tetradecyl sulphate
      and ethanolamine oleate in the sclerotherapy of bleeding oesophageal varices.
AB  - The efficacy and side effects of 3% sodium tetradecyl sulphate (STD) and 5%
      ethanolamine oleate (ETH) were compared in 95 patients admitted with variceal
      bleeding. The patients were allocated in a randomised fashion to one of the
      treatment groups when varices were identified which were either actively bleeding
      or had signs of recent haemorrhage. Endoscopic examination was performed within
      24 hours of admission. The endoscopist had no knowledge of which sclerosant was
      used. Intravariceal injections of 2 ml aliquots up to a maximum of 20 ml were
      made in a double-blinded manner. Repeat injections were performed at weekly
      intervals until all oesophageal varices were obliterated. Bleeding was
      successfully controlled in 42/48 (87.5%) patients in the STD group and 41/47
      (87.2%) patients in the ETH group after one session of therapy. Variceal
      obliteration was achieved after 3.3 +/- 1.3 sessions of STD and 4.5 +/- 1.9
      sessions of ETH (p < 0.05 Student's t-test). Post-injection pyrexia was
      significantly more common in the STD group (42% vs 30% p < 0.05, chi-square
      test). There was no difference in the rates of subsequent oesophageal ulceration,
      stricture formation or perforation of the oesophagus. It is concluded that STD
      and ETH are both effective in controlling variceal haemorrhage, but STD
      obliterates the varices in significantly fewer sessions.

PMID- 8287812
TI  - Percutaneous transcystic cholangioscopy for combined treatment of gallbladder and
      bile duct stones.
AB  - A procedure for percutaneous transcystic cholangioscopy requiring only one
      percutaneous transhepatic fistulous tract to remove stones located in both the
      gallbladder and bile ducts is described. The procedure begins with percutaneous
      transhepatic drainage of the gallbladder or bile duct. Stones in the gallbladder
      and bile duct can be removed under direct vision on transhepatic cholangioscopy.
      Larger stones can be fragmented by electrohydraulic lithotripsy before removal.
      In a preliminary trial the procedure proved to be a feasible method for treatment
      of 13 patients with both gallbladder and bile duct stones as well as septic
      cholangitis who either refused operation or were considered poor candidates for
      surgery. On long-term follow-up (mean period 28 months) stone recurrence was
      observed in three patients.

PMID- 8287813
TI  - Endosonographically-guided fine needle aspiration biopsy of malignant lesions in
      the upper gastrointestinal tract.
AB  - A new method of endoscopic ultrasound (EUS) guided fine needle aspiration using
      an ultrasonic endoscope with a curved array transducer mounted in front of the
      optic lens was developed. As a result of the sector shaped sound field and the
      direction of the scanning plane it was possible to visualise ultrasonically a
      needle inserted through the biopsy channel. EUS guided biopsy was performed in 37
      patients (with 39 lesions) using three types of needles. Based upon initial
      testing of several prototype needles a 160 cm long, 0.8 mm diameter needle placed
      in a Teflon catheter was developed after preliminary results with the first two
      types were unsatisfactory (positive results for malignancy in 3/11 and 4/8
      cases). The third prototype was tested in seven patients with malignant tumours
      of the upper GI tract. In these patients EUS guided biopsy was positive for
      malignancy in 7 of 8 solid lesions. Problems related to the technique and
      criteria for a successful outcome are discussed. The preliminary results show
      that it is possible to advance a needle into a malignant lesion inside or outside
      the GI wall during EUS examination and aspirate material for cytologic
      examination from various lesions. Controlled studies are needed to determine the
      indications for use and the accuracy of the technique.

PMID- 8287814
TI  - Gastric lymphoma: difficult to diagnose, difficult to stage?

PMID- 8287815
TI  - Options in the therapy of gastric lymphoma.

PMID- 8287816
TI  - Idiopathic acute esophageal necrosis: not necessarily a terminal event.
AB  - Idiopathic acute esophageal necrosis (AEN) has been considered a rare event,
      usually having an ischemic origin. Primarily cases from autopsy studies have been
      reported. This report deals with 10 such cases which were diagnosed among some
      80,000 esophago-gastroscopies performed during a 16-year period. Nine patients
      recovered and were discharged from the hospital. The esophageal lesions presented
      as a demarcated, black discoloration which usually evolved to a picture
      suggestive of unspecific esophagitis. Histology invariably revealed diffuse and
      conspicuous necrosis involving the mucosa, submucosa and, frequently, muscular
      layers. In 2 cases, esophageal stenosis developed and, in one case, a full
      thickness necrosis made surgery with colon interposition mandatory.
      Hyperglycemia, hypoxia, carcinoma and ischemic phenomena were found as associated
      conditions. Gastroduodenal, acute ulcerative disease was present in four
      patients. From this experience, it is concluded that AEN is not necessarily a
      terminal phenomenon, notwithstanding that it is usually associated with pre
      existent serious illness. Nevertheless, its etiology remains unknown.

PMID- 8287817
TI  - Through the nose gastroscopy for the placement of feeding tubes.
AB  - Following local anesthesia to the nose, through-the-nose (TTN) passage of a
      paediatric gastroscope was successful and well tolerated in 82 of 92 patients on
      whom it was attempted in order to place nasogastric feeding tubes. This technique
      allows for guidewire placement to be used for insertion tubes or dilators. The
      ten failures we observed occurred in patients with bilateral narrow turbinates.
      We conclude that the TTN approach is quicker and easier than conventional methods
      of feeding tube placement allowing for an additional endoscopic evaluation of the
      upper GI tract.

PMID- 8287818
TI  - Upper digestive hemorrhage as clinical presentation of leukocytoclastic
      vasculitis: an unusual endoscopic diagnosis.

PMID- 8287819
TI  - Double synchronous squamous carcinoma of the esophagus.

PMID- 8287820
TI  - Endoscopic removal of recurrent duodenal hamartoma.

PMID- 8287821
TI  - Endoscopic treatment of broncho-esophageal fistulae: personal experience.

PMID- 8287822
TI  - Extraction of an accidentally diagnosed foreign body in the stomach during
      routine endoscopy for symptoms suggestive of rapid onset ulcer.

PMID- 8287823
TI  - Upper gastrointestinal bleeding due to hookworms (Ancylostoma duodenale)--a case
      report.

PMID- 8287824
TI  - Severe whipworm infestation: a rare cause of inflammatory dysenteric bowel
      disease.

PMID- 8287825
TI  - The difficult pylorus--an easy way in.

PMID- 8287826
TI  - Biliary ascariasis: endoscopic extraction of a living worm from the bile duct.

PMID- 8287827
TI  - Peritonitis after colonoscopy in a patient with ascites.

PMID- 8287828
TI  - Chronic N-methyl-D-aspartate administration prevents melatonin-associated changes
      in cell differentiation in the harderian glands of male hamsters.
AB  - The daily administration of 25 micrograms of melatonin for 10 weeks resulted in
      an increase in the percentage of Type II cells in the Harderian glands of male
      Syrian hamsters. Harderian glands of melatonin injected animals consisted of 65
      70% Type II cells while control animals which were injected with saline had 40%
      Type II secretory cells. The daily administration of 3 mg of the glutamate
      receptor agonist N-methyl-D-aspartate (NMDA) prevented the effects of melatonin
      on cell differentiation but was without effect when administered to saline
      treated hamsters alone. Both the relative number of mitoses and the number of
      total cells, estimated by counting the nuclei, was not affected. Thus, a
      conversion from Type I to Type II cells seems possible. The effects of melatonin
      and NMDA administration were independent of the serum levels of testosterone,
      luteinizing hormone and thyroxine, hormones which have been implicated in Type II
      cell differentiation. However, prolactin levels, which were affected by melatonin
      and NMDA administration, might be involved in the differentiation of Harderian
      gland secretory cells.

PMID- 8287829
TI  - Sp-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'-cyclic
      monophosphorothioate is a potent stimulus for insulin release.
AB  - The Sp-isomer of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'-cyclic
      monophosphorothioate (Sp-5,6-DCl-cBIMPS) at micromolar concentrations was a more
      potent stimulus for insulin release than 8-bromo-cyclic (c) AMP in isolated
      pancreatic islets of the rat. Sp-5,6-DCl-cBIMPS increased basal secretion, and
      potentiated glucose-stimulated insulin release to levels similar to those evoked
      by glucagon. A ten-fold higher concentration of 8-bromo-cAMP was required to
      mimic the potentiating effects of Sp-5,6-DCl-cBIMPS. Neither 8-para
      chlorophenylthio-cGMP, 8-bromo-cGMP, nor dibutyryl-cGMP affected insulin release.
      Thus, Sp-5,6-DCl-cBIMPS is a potent and specific stimulus for cAMP-mediated
      insulin release.

PMID- 8287830
TI  - Elevated plasma levels of VWF:Ag in hyperthyroidism are mediated through beta
      adrenergic receptors.
AB  - Thyroid dysfunction influences the levels of Von Willebrand factor (VWF:Ag).
      Plasma VWF:Ag levels in 35 hyperthyroid patients were significantly elevated,
      which had a positive correlation with both T3 (Triiodothyronine) and T4
      (Thyroxine) levels. A follow-up study of seven hyperthyroid patients undergoing
      anti-thyroid therapy showed that the elevated VWF:Ag levels returned to normal
      range with the normalization of thyroid function. On the other hand, after
      administration of 160 mg/day of propranolol, a specific blocker of beta
      adrenergic receptors, to five hyperthyroid patients for twenty-eight days, plasma
      VWF:Ag levels returned to normal range, while T3, T4 levels remained high without
      significant alteration. These results demonstrated that the elevation of plasma
      VWF:Ag by thyroid hormone is mediated through beta-adrenergic receptors, which
      may be useful to further understand the physiological and pathological roles of
      thyroid hormone in the regulation of VWF:Ag levels.

PMID- 8287831
TI  - Alterations of gammacarboxyglutamic acid in formic acid and guanidine extracts in
      phosphate-deficient rat bone.
AB  - We developed rickets and osteomalacia in rats by means of a low phosphorus,
      normal calcium and normal vitamin D diet, causing severely inhibited
      mineralization. The concentrations of gammacarboxyglutamic acid (Gla) in 10%
      formic acid and 5M guanidine extracts were studied in normal and phosphate
      deficient rat bone. Although the Gla concentration in the formic acid extract was
      constant for both groups, it decreased in the guanidine extract of the phosphate
      deficient group. The Gla content of the guanidine extract reflected a lower
      concentration of Gla-containing proteins, one of which, matrix Gla protein (MGP),
      acts as a mineral deposition inhibitor. Thus, the production of MGP decreased in
      the impaired mineralization of bone. The quantification of Gla in formic acid and
      guanidine extract is useful in studying the Gla-containing proteins, osteocalcin
      and MGP.

PMID- 8287832
TI  - Homeorhetic actions on tissue protein metabolism after the administration of rat
      growth hormone to normal rats.
AB  - An acute treatment with rat growth hormone (1 microgram/g) to intact female rats
      produced immediate changes in muscle and bone protein synthesis as well as in
      muscle protein breakdown, while glucose and glutamate-piruvate transaminase
      plasma levels were not altered. These effects, apparently, are not mediated by
      systemic insulin-like growth factor I. Also a long-term treatment with
      somatotropin (0.1 microgram/g/d) for 22 days was performed, in which protein
      synthesis rates in muscle, liver and bone remained unchanged. However, the growth
      hormone long-term treatment induced a decrease in muscle proteolytic activity and
      an increase in tibia weight. In this context, this experiment describes,
      apparently for the first time, the systemic effect of growth hormone in entire
      female rats. Data suggest that a single dose of rat growth hormone produces
      immediate changes in tissue protein metabolism, through a direct effect of growth
      hormone. These effects were not observed after the long-term growth hormone
      treatment, although these animals showed an increased in tibia proportions.

PMID- 8287833
TI  - In vitro effect of ethanol on LH and FSH secretion by pituitary glands of female
      rats.
AB  - The effect of ethanol (EtOH) on LH and FSH release in vitro has been studied in
      order to determine whether the effect of alcohol observed in vivo could be
      mediated by a direct action at the level of the anterior pituitary. Pituitary
      glands were incubated for 4 hours in TC-199 medium with or with 100 mM ethanol.
      Basal gonadotrophin release was examined as well as secretion stimulated by
      luteinizing hormone releasing hormone (LHRH) in the presence or absence of
      cycloheximide. The total amount of LH and FSH released during the incubation
      period was calculated. Ethanol did not significantly alter basal gonadotrophin
      release or LHRH-stimulated FSH release. However, LH secretion induced by LHRH was
      decreased by EtOH when compared to the LHRH-stimulated group. Cycloheximide
      decreased the LHRH-stimulated release of LH and FSH but this effect was not
      altered by EtOH. The results show that EtOH alters the release but not the
      synthesis of gonadotrophins by a direct effect on the anterior pituitary gland.

PMID- 8287834
TI  - Diabetes prevents the normal responses of the ovary to FSH.
AB  - FSH in vitro stimulates increased oxygen uptake by isolated follicular granulosa
      cells from immature rats treated with diethylstilbestrol (DES) when substrates
      are present (glucose, glutamate, pyruvate or fumerate) or are completely absent.
      However, when glucose is the only substrate or when any single substrate is
      omitted from the buffer, FSH has no effect. FSH in vitro also increases the
      uptake of glucose and the formation of 14CO2 from [1-6 14C]-glucose. Granulosa
      cells from diabetic immature rats treated with DES did not show increased oxygen
      uptake with in vitro FSH. Diabetic cells had similar receptor binding of FSH to
      that of control non-diabetic cells. The addition of both insulin and FSH in vitro
      to buffer with diabetic granulosa cells gave increased oxygen uptake over that of
      control cells from diabetic rats. The insulin stimulation of oxygen uptake by FSH
      in cells from diabetic rats was not duplicated by either epidermal growth factor
      (EGF) or insulin-like growth factor I (IGF-1). Follicle counts of ovaries from
      diabetic and control immature rats treated with DES showed increased atresia in
      the diabetic ovaries after only 44 hr. of diabetes. Follicle counts of ovaries
      from adult diabetic rats showed increased atresia in 24 hours after induction of
      diabetes at proestrus. Follicle counts of pseudopregnant rats showed increased
      atresia by 3 days after diabetes was induced. We conclude that diabetes prevents
      normal follicle growth stimulated either by exogenous DES or by endogenous
      hormones secreted during proestrus.

PMID- 8287835
TI  - Measures of skeletal muscle calcium channels and acetylcholine receptors in
      thyroidectomized rats.
AB  - Hypothyroidism frequently presents with muscle complaints. No consistent
      histopathology nor electrophysiology explains these symptoms and signs. As well,
      no previous study shows specific changes in components of the nerve-muscle
      synapse nor excitation-contraction coupling in adult muscles, but changes are
      seen in hormone-treated embryonic myoblasts. In this study, adult male Holtzman
      rats underwent thyroidectomy and their age-matched euthyroid controls were
      simultaneously subjected to sham operation. Thirty days post-operative, animals
      were sacrificed for anterior tibialis muscles harvest. Muscle dihydropyridine
      type calcium channel (isradipine) and acetylcholine receptor (alpha-bungarotoxin)
      binding were measured and compared between experimental treatment groups. There
      were no significant differences in either the affinity or density of isradipine
      binding. However, hypothyroid muscles showed a nearly 50% reduction in
      acetylcholine receptor density when compared to control muscles. Thyroidectomy is
      associated with specific effects on components of neuromuscular transmission in
      adult fast twitch muscle.

PMID- 8287836
TI  - Effect of L-thyroxine and carbimazole on brain biogenic amines and amino acids in
      rats.
AB  - Effect of L-thyroxine and carbimazole on brain biogenic amines and amino acids
      content and circulating levels of thyroid hormones has been investigated in rats.
      L-thyroxine treatment caused marked elevation of 5-HT, histamine and glutamate
      along with the decline in the level of GABA whereas administration of carbimazole
      had a contrary effect on rat hypothalamus. Further, L-thyroxine administration
      also raised histamine as well as glutamate content and decreased GABA level in
      thalamic region of the rat brain but carbimazole treatment reduced 5-HT and
      glutamate content in this area of the rat brain. Similarly, cortical content of 5
      HT and histamine also increased following L-thyroxine administration whereas
      carbimazole treatment lowered 5-HT, histamine and glutamate levels.
      Simultaneously, there was a considerable rise in the circulating levels of T3 and
      T4 in L-thyroxine-treated rats and a marked reduction in their levels in
      carbimazole-treated rats. There is a positive correlation between these amines
      and the thyroid hormone level. Thus, the results suggest that L-thyroxine and
      carbimazole administration cause marked alteration in biogenic amines and amino
      acids in rat brain, which may have an important role in the functioning of
      thyroid gland.

PMID- 8287837
TI  - Daily selenium intake estimates for residents of arsenic-endemic areas.
AB  - The selenium in the diet of persons in arsenic-endemic areas, high levels of
      arsenic in the drinking water, was evaluated. The methodology used was that of 24
      hr dietary recall. Daily selenium intakes of two rural towns in northern Mexico
      were found to be similar, approximating 72.9 and 60.6 micrograms. These values
      were similar to those of a previously arsenic-exposed area from California,
      Edison community. The Edison participants had a daily selenium intake of 61.8
      micrograms. The possible negative effect of selenium to produce differences in
      reported geographical variation in disease could not be substantiated in this
      study. Other nutrient intakes, protein and energy were also found similar for
      communities. Differences were noted in vitamin A intake where one-third the daily
      requirement was experienced by Mexican participants compared to two-thirds the
      requirement being satisfied by those participants from Edison.

PMID- 8287838
TI  - Ferruginous bodies as markers of environmental exposure to inorganic particles:
      experience with 270 autopsy cases in Mexico.
AB  - Ferruginous bodies (FB) were quantified in lung digests from 270 autopsy cases
      over 20 years of age. The cases were autopsied in three different hospitals of
      the Secretaria de Salud, Mexico, DF. Two hundred seventy samples of peripheral
      lung tissue were digested in commercial bleach, and all morphologic types of
      ferruginous bodies were quantified. The results showed that numbers of
      ferruginous bodies per gram of dry tissue increased over the years: 4.2 FB/g in
      cases from 1975 to 42.5 FB/g in cases from 1988 (r = 0.86). Higher counts of
      ferruginous bodies were seen in males, smokers, and Mexico City dwellers.
      However, more than 70% of them presented less than 100 FB/g. Our study
      demonstrates that most of our cases had a nonoccupational exposure to fibers.

PMID- 8287839
TI  - Genotoxicity to human cells induced by air particulates isolated during the
      Kuwait oil fires.
AB  - In an effort to examine the potential of exposure to soot from the 1991 oil fires
      in the Kuwait desert for inducing genetic effects we studied the in vitro
      genotoxicity of this material. Air particulates isolated near the Kuwait oil
      fires were studied using three assays. Dose-dependent increases were observed for
      both sister chromatid exchanges in human peripheral blood lymphocytes and
      mutation at the hprt locus in the metabolically competent human lymphoblast cell
      line AHH-1. Similar magnitudes of response were seen using these two assays when
      testing a standard air particulate sample which had been isolated from the
      Washington, DC, area. Using the 32P-postlabeling assay, no increase in DNA adduct
      formation was observed in AHH-1 cells treated with particulates isolated from
      sampling in Kuwait.

PMID- 8287840
TI  - What are people dying of on high air pollution days?
AB  - The air pollution disasters in London in 1952, the Meuse valley in 1930, and in
      Donoroa, Pennsylvania, in 1948 made it clear that extremely high levels of
      particulate-based smog could produce large increases in the daily mortality rate.
      Recent studies of fluctuations in daily air pollution and daily mortality have
      reported associations at much lower concentrations in London during the 1960s and
      in Philadelphia, Steubenville, Santa Clara, St. Louis, Utah valley, Detroit, and
      eastern Tennessee in the 1970s and 1980s. Whether these associations are causal
      or not is a matter of considerable public health concern. If the detailed pattern
      of the deaths at these lower concentrations appeared similar to the pattern in
      London, this would strengthen the argument for causality. To examine this issue,
      the death certificates from Philadelphia were examined on the 5% of the days with
      the highest particulate air pollution and the 5% of the days with the lowest
      particulate air pollution during the years 1973-1980. There was little difference
      in weather between the high and low pollution days, but total suspended
      particulate matter concentrations averaged 141 micrograms/m3 on the high
      pollution days versus 47 micrograms/m3 on the low pollution days. The relative
      risk of dying on the high pollution days was 1.08 P < 0.0001. The relative
      increase was higher for COPD (1.25) and pneumonia (1.13). Deaths were also
      elevated for heart disease and stroke; however, there was a substantial increase
      in the reports of respiratory factors as contributing causes for those underlying
      causes of death. Dead-on-arrival deaths and deaths outside of hospitals and
      clinics were also disproportionately increased. This paralleled the pattern seen
      in London in 1952. The age pattern of the relative risk of death was also
      similar. This adds to the evidence that the association is causal.

PMID- 8287841
TI  - Air pollution and daily mortality: a review and meta analysis.
AB  - The air pollution disaster in London in 1952 established that very high levels of
      particulate-based smog can cause dramatic increases in daily mortality. Recently,
      more than a dozen studies at much lower particle concentrations have reported
      evidence that exposure to lower levels of airborne particles results in smaller,
      but nonzero increases in daily mortality. These studies were examined in a meta
      analysis. A primary focus of the meta-analysis was to examine effect size
      estimates across large differences in both the levels of potential confounding
      factors and in their correlation with airborne particle concentration. In the
      primary meta-analysis, airborne particle concentration was a significant risk
      factor for elevated mortality (RR = 1.06, 95% CI = 1.05-1.07). The relative risk
      is for a 100 micrograms/m3 increase in TSP concentration. While mortality peaked
      in the cold months in all locations, in the majority of the studies airborne
      particle concentrations were highest in the warm months, indicating that seasonal
      patterns were not responsible for the observed associations. The relative risk
      was 1.06 (95% CI = 1.05-1.07) when the analysis was restricted to cities with
      summer peaking pollution. The relative risk was identical in cities with above
      average annual temperatures and cities with colder climates. It was also
      identical in drier and more humid climates, and similar across a wide range of
      correlations between temperature and airborne particle concentrations. These
      results suggest that inadequate weather control was not responsible for the
      association. A detailed examination of data from Philadelphia showed that control
      for season and weather was adequate for removing all long-term seasonal and
      subseasonal patterns from the mortality data, and that using a very flexible
      nonlinear fit to the weather factors did not disturb the association with TSP.
      The most reasonable interpretation of this pattern of results is that the
      association is causal. This is supported by other studies which have reported
      that particulate air pollution was associated with lung function deficits,
      increased symptoms, and increased hospitalization.

PMID- 8287842
TI  - Structural equation modeling and nested ANOVA: effects of lead exposure on
      maternal and fetal growth in rats.
AB  - This study provided an assessment of the effects of lead on early growth in rats
      based on structural equation modeling and nested analysis of variance (ANOVA).
      Structural equation modeling showed that lead in drinking water (250, 500, or
      1000 ppm) had a direct negative effect on body weight and tail length (i.e.,
      growth) in female rats during the first week of exposure. During the following 2
      weeks of exposure, high correlation between growth measurements taken over time
      resulted in reduced early postnatal growth. By the fourth week of exposure,
      reduced growth was not evident. Mating began after 8 weeks of exposure, and
      exposure continued during gestation. Decreased fetal body weight was detected
      when the effects of litter size, intrauterine position, and sex were controlled
      in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal
      development, possibly because lead did not alter maternal serum calcium and
      phosphorus levels. The effect of lead on individual fetal body weight suggests
      that additional studies are needed to examine the effect of maternal lead
      exposure on fetal development and early postnatal growth.

PMID- 8287843
TI  - Tests of the linear-no threshold theory for lung cancer induced by exposure to
      radon.
AB  - The linear theory used to extrapolate the cancer risk of radon exposure from high
      levels where direct data are available to low levels encountered in homes is
      tested by comparing lung cancer rates, m, and average radon levels, r, in
      numerous U.S. states and counties. It is shown that most problems normally
      associated with ecological studies do not apply here. The data show a very strong
      tendency for lung cancer rates, corrected for smoking prevalence (S), to decrease
      with increasing r, in sharp contrast to the opposite behavior predicted by the
      theory. It is shown that even a perfect negative r-S correlation cannot explain
      this discrepancy. Actual r-S correlations are only a few percent. Several other
      possible explanations for the discrepancy are explored, but none can reduce it by
      more than about 25%.

PMID- 8287844
TI  - Drinking water mutagenicity in past exposure assessment of the studies on
      drinking water and cancer: application and evaluation in Finland.
AB  - The assessment of past exposure is a prerequisite to all epidemiological studies
      on drinking water and cancer. In this study the past exposure assessment of
      drinking water carcinogenicity was done in terms of the drinking water
      mutagenicity estimated from historical water parameters and compared with the
      methods used previously in past exposure assessments in studies on drinking water
      and cancer. The method was applied in 56 municipalities in Finland. The
      comparison of different methods in past exposure assessment suggests some
      advantages for the method presented as it allows a quantitative exposure
      assessment based on historical information on drinking water mutagenicity.
      Nevertheless the relevance of the method is with respect to the role of
      mutagenicity in carcinogenicity and the water type in question.

PMID- 8287845
TI  - Lipid peroxidation.

PMID- 8287846
TI  - Validation of a short dietary questionnaire and a qualitative fat index for the
      assessment of fat intake.
AB  - In connection with a population-based study on familial and non-familial
      determinants of serum total cholesterol an interviewer-administered short
      questionnaire, including 21 food items, and a qualitative fat index based on four
      questions were developed. Subjects for the validation study, 51 women and 31 men,
      aged 16-71 years, were selected from the population-based study (n = 892). The
      short questionnaire and the qualitative fat index were validated with a 3 day
      food record as the reference method. The short questionnaire captured 90-97% of
      the mean intakes of total fat, saturated, monounsaturated and polyunsaturated
      fatty acids and cholesterol. The Pearson correlation coefficients between the fat
      intakes based on the questionnaire and the diet records were strongest for the
      intake of total fat (r = 0.80). The qualitative fat index was based on four
      questions concerning type of fat: the higher the scores the higher the intakes of
      polyunsaturated fatty acids. The Spearman correlation coefficients between the
      qualitative fat index and the intakes based on the diet records were -0.55 for
      saturated, 0.34 for monounsaturated and 0.52 for polyunsaturated fatty acids. The
      respective correlation for the P/S ratio (total amounts of polyunsaturated fatty
      acids/saturated fatty acids) and the PM/S ratio (total amounts of polyunsaturated
      and monounsaturated fatty acids/saturated fatty acids) were 0.50 and 0.53. An
      inverse association between serum total cholesterol and the qualitative fat index
      was found in the whole study population, suggesting the impact of dietary fat on
      serum cholesterol in this study population. In conclusion, the short
      questionnaire proved to be accurate in measuring the intake of different fatty
      acids at the group level, whereas the simpler fat index measured the quality of
      fat quite well.

PMID- 8287847
TI  - Cholesterol-lowering diets may increase the food costs for Danish children. A
      cross-sectional study of food costs for Danish children with and without familial
      hypercholesterolaemia.
AB  - Food costs for 30 children under dietary treatment for familial
      hypercholesterolaemia were compared with those of 105 other Danish children. The
      daily intake of macronutrients and the daily cost of the diet for each child were
      calculated from dietary intakes and average prices of 365 different food items.
      The mean +/- SE percentages of energy (E%) from fat in the diet of children with
      and without known familial hypercholesterolaemia were 23.6 +/- 0.8 E+ and 34.5 +/
      0.5 E%, respectively (P < 0.001). The dietary costs per MJ in these two groups
      were 3.79 +/- 0.12 Danish crowns (DKr) and 3.34 +/- 0.05 DKr (P < 0.001), taking
      into account food wastage due to preparation and cooking. The cost per unit of
      energy increased with decreasing fat energy percentage of the diet for all
      children as one group (r = -0.37, P < 0.001), as well as for the group of
      children without familial hypercholesterolaemia (r = -0.35, P < 0.001). Stepwise
      multiple regression analysis showed that the differences in cost per MJ between
      the groups could be explained primarily by differences in percentage of energy
      from fat. We conclude that a reduction of dietary fat from 35 E% to 25 E% may
      increase food costs by 10-20% for Danish children.

PMID- 8287848
TI  - Nutritional status and immunocompetence in eating disorders. A comparative study.
AB  - Nutritional status and immunocompetence were evaluated in 26 patients suffering
      from anorexia nervosa (AN) (n = 16) or bulimia nervosa (BN) (n = 10) in
      comparison with a control group (n = 22). Body mass index (BMI) was lower in all
      patients than in controls, AN patients having the lowest values. Slight
      leukopenia together with relative lymphocytosis was shown in both AN and BN. The
      CD4/CD8 ratio was low in all patients, but more so for BN patients, although cell
      mediated immune function was impaired to the same extent for both eating
      disorders. The complement system appeared to be damaged in all the patients in
      comparison with controls. These results may mean that the nutritional status of
      both syndromes was different. Although anthropometric measurements in the BN
      group may suggest a more acceptable nutritional status, immunological parameters
      were shown to be depleted at the same level as the AN group and even more
      impaired when judged by the lower CD4/CD8 values.

PMID- 8287849
TI  - Diet and dental caries in preschool children.
AB  - A study was carried out in two New Zealand cities with a fluoridated water
      supply, to look at the dietary habits of preschool children and to investigate
      whether any dietary factors or other variables are associated with dental decay
      in the deciduous teeth of these children. From a final study of 355 (a 59%
      response rate), demographic data, a dental examination, a series of three 24 h
      recalls over a period of 1 year, and a food frequency questionnaire to cover the
      same 1 year interval were collected. The sample included 93 children with dental
      decay and 262 caries-free children, matched for age, sex and sociodemographic
      variables. The energy and nutrient intakes of the preschool children were
      sufficient to support normal growth. The main sources of dietary energy in the
      diets of this study group came from bakery and dairy products. Boys had slightly
      higher mean intakes of most nutrients than girls. No significant differences were
      found in the food patterns or intakes of macronutrients between the children of
      this study group with caries and those without. There was an inverse relationship
      between social background and dental health, with increasing social advantage
      being associated with decreasing dental health problems. Syrup medicines and, in
      particular, antibiotic syrups independently increased the risk that a child would
      have a number of carious lesions, especially if taken frequently.

PMID- 8287850
TI  - Vitamin B12 and folate status in human immunodeficiency virus infection.
AB  - Vitamin B12 and folate status were determined in 35 male HIV seropositive
      patients. Of these, 16 were asymptomatic (CDC II/III) and 19 were symptomatic
      (CDC IV) according to the Centre for Disease Control (CDC) Classification.
      Deviations from normal values for serum B12, serum folate and red cell folate
      were not a common finding in this sample of patients. No patient had low serum
      B12. One CDC IV patient and two CDC II/III patients were found to have raised
      serum B12. Dietary intake of vitamin B12 was well above the Reference Nutrient
      Intake for all patients. Three patients displayed low folate values (one CDC IV
      patient had low serum folate, one had low red cell folate and one CDC II/III
      patient had both). No patient displayed elevated serum or red cell folate. Only
      56% of the CDC II/III and 36% of the CDC IV group were meeting the Lower
      Reference Nutrient Intake for folate. The only significant difference between the
      CDC II/III group and the CDC IV group was a lower red cell folate (although
      within the normal laboratory range) in the CDC IV group. There was no significant
      difference in dietary intake and haematological status between the drug users and
      the homosexuals.

PMID- 8287851
TI  - Loss of body mass in ex-prisoners of war.
AB  - Body mass was examined in the defenders of Vukovar (n = 71) from eastern
      Slavonia, Republic of Croatia, immediately on release from enemy concentration
      camps. The sample consisted of a group of 33 male smokers who had been imprisoned
      for (mean +/- SD) 127.4 +/- 18.4 days (age 31.6 +/- 7.2 years) and 38 male
      smokers, imprisoned for 271.6 +/- 14.4 days (age 30.8 +/- 6.5 years). According
      to subjective estimations the prisoners of war had lost 18.4 +/- 6.1% and 21.6 +/
      10.2% respectively, in relation to body mass before the war. For comparison data
      were used on a healthy population of male smokers from eastern Slavonia
      (Vinkovci, Republic of Croatia (n = 75) aged 32.4 +/- 5.2 years taken from a
      study carried out in 1976. Data were analysed on body mass, body mass index,
      triceps, subscapular skinfolds and percentage of body fat. All parameters were
      statistically significantly lower in males imprisoned for 271.6 +/- 14.4 days in
      relation to the comparative group (P < 0.0001-0.05). A negative deviation from
      body mass nomogram was registered in prisoners of war in relation to the
      comparative group (5-16%). Basic biochemical parameters were examined in the
      prisoners of war. In the group imprisoned for 127.4 +/- 18.4 days statistically
      significant differences and pathological values of mean corpuscular volume and
      haematocrit were verified in relation to the group of prisoners with longer
      duration of imprisonment (P < 0.001). Although the prisoners of war had lost
      weight during imprisonment in the camps due to the frugal diet no clinical signs
      of malnutrition were found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287852
TI  - Drinking water with a meal: a simple method of coping with feelings of hunger,
      satiety and desire to eat.
AB  - This study examined whether drinking of water with breakfast affects the feelings
      of satiety and hunger, and how long after the meal this effect is maintained.
      Eight healthy, normal-weight women had three breakfasts with two extra glasses (4
      dl) of water and three similar breakfasts without water. The breakfasts were
      served on three successive mornings during a 2 week period. The subjects filled
      in forms with visual analogue scales on feelings of hunger, satiety and desire to
      eat. The forms were filled just before the breakfast, in the middle of the
      breakfast before and after drinking of water, after finishing the meal, and
      thereafter every 30 min until 11.15 a.m. The results show that drinking two
      glasses of water affects subjective feelings of hunger and satiety during the
      meal, but this effect is not maintained after the meal. It is suggested that
      during a meal subjective feelings of hunger and satiety change independently of
      the food energy consumed. This study allows, however, no conclusions on the
      possible influence of drinking water on actual food intake during and after a
      meal.

PMID- 8287853
TI  - Influence of polar route schedules on the duty and rest patterns of aircrew.
AB  - The duty and rest periods of aircrew operating the polar route from London via
      Anchorage were recorded during five schedules which involved 1-, 2- or 3-day
      sojourns in Japan. Sleep throughout each schedule was fragmented, with naps
      before duty and short sleeps after arrival at a new location. Sleep disturbance
      rather than cumulative sleep loss appeared to be the overriding problem, and the
      shorter schedules had the most marked disturbances in sleep during the trip and
      during the immediate recovery period. Electroencephalographic studies are
      necessary to confirm these observations, and information on circadian rhythmicity
      is needed to define the circumstances which lead to persistence of sleep
      disturbance on return to Europe.

PMID- 8287854
TI  - The prediction of recommended energy expenditure for an 8 h work-day using an air
      purifying respirator.
AB  - Thirty railway workers executed maximal, or near maximal, stress tests with and
      without the use of a half mask air-purifying respirator (Spasciani 85 A1 P1)
      fitted with two combined filters for simultaneous protection from organic vapours
      and particulate matter. The pressure-flow characteristics of inspiratory and
      expiratory resistance at airflows in the range 0-90 l.min-1 were established by a
      continuous flow method on one test mask. Significant differences were found by
      paired t-test between the two exercises (with and without use of mask), showing
      reduced values with use of the mask, for breath frequency, ventilation rate,
      oxygen uptake, carbon dioxide production, maximal oxygen uptake, percentage of
      maximal voluntary ventilation used at the maximal exercise ventilation. No
      significant differences were found for tidal volume, respiratory quotient, heart
      rate, systolic blood pressure, oxygen uptake at anaerobic threshold, and duration
      of exercise. The predicted energy expenditure recommended for an 8 h work shift,
      corresponding to 40% of maximal oxygen uptake, is found to be reduced working
      with respirator and is significantly different from that observed during stress
      test without mask. The average ventilation rate at this workload is below 25
      l.min-1, with predicted inspiratory mouth pressure equal to, or less than, 20 mm
      H2O. This maximal inspiratory mouth pressure is proposed as a safety limit for
      prolonged work using a respirator, with a recommended energy expenditure close to
      40% of maximal oxygen uptake.

PMID- 8287855
TI  - The influence of load knowledge on lifting technique.
AB  - The purpose of this study was to analyse the influence of load knowledge on
      lifting technique. Ten men lifted a box containing either no weight or weights of
      150, 250 or 300 N with and without knowledge of what was inside the box. The
      kinetics and kinematics of the lift were analysed using a force plate, an
      optoelectronic motion analysis system, and a rigid body link model. At 0 N
      lifting, the unknown load resulted in a jerk-like motion and a significantly
      increased peak L5-S1 flexion-extension moment. At 150 N there was also a
      significant increase in the speed of trunk extension with unknown weights, but
      the L5-S1 moment remained unchanged. At higher load levels there were only minor
      differences between lifting techniques when knowing and not knowing the load. We
      conclude that lifts are approached assuming a certain weight, and that when the
      assumption is wrong and the load lighter than anticipated lifting is performed
      with a 'jerking' motion, creating unnecessary loads on the lower back.

PMID- 8287856
TI  - A comparison of methods of estimating anaerobic work capacity.
AB  - The hyperbolic relationship between power output (P) and time to exhaustion (t)
      is described as: (P-theta PA).t = W', where theta PA is the power asymptote (or
      'critical power'), which theoretically represents the highest sustainable power
      output, and W' is a constant which represents a limited amount of work which can
      be performed above theta PA (or 'anaerobic capacity'). The purpose of this study
      was to determine the validity of W' as anaerobic capacity, using maximal oxygen
      deficit as the criterion measure. Thirteen women (mean (+/- SD) age 23 +/- 2
      years, height 1.67 +/- 0.07 m and mass 60.8 +/- 8 kg) and 13 men (mean age 23 +/-
      2 years, height 1.74 +/- 0.1 m and mass 71.3 +/- 14 kg) performed two sets of
      five bouts of high-intensity cycling exercise to exhaustion, each bout on a
      separate day and at a different relative power. Individual W' were calculated by
      nonlinear regression of time with power, with time as the dependent variable.
      Oxygen deficit was determined during each bout, and the mean of the values
      obtained from the power output which elicited the highest values was used as the
      criterion for anaerobic capacity. Mean (+/- SE) values for anaerobic capacity for
      women were 179 +/- 10 J.kg-1 (W') and 177 +/- 10 J.kg-1 (oxygen deficit) and for
      men, 224 +/- 10 J.kg-1 (W') and 235 +/- 9 J.kg-1 (oxygen deficit). The W'
      estimates and criterion measures were the same (F1,24 = 0.61, p = 0.44), and
      there was no method-gender interaction (F1,24 = 0.26, p = 0.62).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8287857
TI  - College students' attitudes and knowledge of AIDS.
AB  - To determine attitudes and knowledge of AIDS, a survey was conducted among
      students at the Gondar College of Medical Sciences, Gondar, Ethiopia. One hundred
      sixty four new incoming students (115 males, 49 females) in all departments in
      1990-91 academic year provided information. The results reveal that 40% of the
      students have experienced sexual intercourse. Their knowledge of AIDS was
      adequate and comparable with other college and high school students, but the
      majority of those who practice sex do not use condoms and a fifth have had a
      sexual contact with a high risk individual.

PMID- 8287858
TI  - Maternal mortality in rural communities of Illubabor, southwestern Ethiopia: as
      estimated by the "sisterhood method".
AB  - In this study, the "sisterhood method", a new indirect technique, utilizing a
      cross-sectional survey by retrospective recall for deriving population-based
      estimates of maternal mortality for rural communities, was used in rural
      Illubabor region, Southwestern Ethiopia, in December 1991. The findings indicate
      a lifetime risk of maternal mortality of 0.0426, or 1 in 23 women; approximating
      a maternal mortality ratio of 570 per 100,000 live-births. The communities
      experience high maternal mortality which is compounded by high fertility as
      reflected by the total fertility rate of 7.6. The method can readily be applied
      to our settings to estimate the lifetime risk of maternal mortality and derive
      the maternal mortality ratio. In order to generate awareness, support planning
      and intervention strategies, community-based estimates of maternal mortality will
      remain a priority where vital events registration is non-existent and health
      service statistics are not reliable.

PMID- 8287859
TI  - Prevalence of anaemia in pregnancy in Jima town, southwestern Ethiopia.
AB  - A prospective study of the prevalence of anaemia in pregnancy among 279 first
      time attendants of the antenatal care clinic at Jima Health Centre, Jima,
      Ethiopia was carried out from August 20 to December 15, 1991. The overall
      prevalence of anaemia was 41.9%, the rates being 56.8% and 35.9% for rural and
      urban residents respectively. The mean haemoglobin level was 10.9 gm/dl and 6.4
      gm/dl for the whole group and anaemic women respectively. The majority (74.3%)
      had moderate anaemia; 2.5% had severe anaemia. The rate of anaemia was higher
      among the illiterate and in those who did not practice family planning of any
      sort and in the third trimester, and increased with parity.

PMID- 8287860
TI  - Schistosoma haematobium infection among Ethiopian prisoners of war (1977-1988)
      returning from Somalia.
AB  - Fifty Ethiopian male prisoners of war aged 20-34 years returning from Somalia
      were examined at the Schistosomiasis Diagnostic Laboratory of the Institute of
      Pathobiology, Addis Abeba University, Addis Abeba in 1988. Medical history was
      obtained and their urine was examined by the filtration technique. Recovered eggs
      of S. haematobium were allowed to hatch as a test for viability. Positive
      patients were treated with praziquantel at a single dose of 40mg per kg. 94% of
      the prisoners gave history of haematuria and 96% gave history of treatment for
      schistosomiasis while in Somalia. S. haematobium egg positivity rate was 30% and
      all but one patient had viable eggs in their urine. The geometric mean egg count
      per 10ml urine was only 6.4. Urine examination of treated cases six weeks later
      showed 100% cure rate. A preliminary compatibility study between Ethiopian
      Bulinus snails and the Somalian strain of S. haematobium showed that B.
      abyssinicus and B. truncatus were susceptible to the parasite while B. africanus
      was only partially susceptible. The possibility that a foreign strain of S.
      haematobium may be introduced into ecologically and malacologically receptive
      areas in Ethiopia is discussed.

PMID- 8287861
TI  - Tuberculin conversion in children after BCG vaccination.
AB  - Tuberculin sensitivity after BCG vaccination was studied in 86 children aged 6 to
      24 months at W/o Beletshachew Abbajobire Mother and Child Health Centre, Addis
      Abeba from July 22-August 23, 1992. The overall conversion rate was 59%, of whom
      75% showed indurations not exceeding 10mm. The study confirmed that the positive
      response in the Mantoux test due to BCG immunization usually produces less than
      10mm of induration. Complications of BCG vaccine were observed in only one child
      (1.2%). Those children who did not react to the test positively (41%) were given
      re-vaccination with BCG. The study suggests that a Mantoux test should be the
      usual practice after BCG immunization.

PMID- 8287862
TI  - Plasmodium falciparum sensitivity to antimalarials at Humera, northwestern
      Ethiopia.
AB  - Between September 5 and 25, 1991, the susceptibility of P. falciparum to
      chloroquine and sulfadoxine-pyrimethamine (SP) was measured in vivo in 47 semi
      immune cases at Humera-Northwestern Ethiopia using the simplified in vivo test.
      The objective of the study was to obtain baseline data, and to suggest first and
      second line drugs. A 25mg/kg dose of chloroquine base was administered over a
      three-day period to 23 cases of P. falciparum malaria with a minimum of 25
      rings/300 white blood cells. All showed results consistent with sensitivity. The
      same was true for all 24 cases who received a single curative dose of SP. None of
      the cases had recrudescence within seven days follow-up, indicating that RII and
      RIII levels of resistance were absent. Further follow-up using the extended test
      (28 days) was not carried out since transmission cannot be excluded under field
      conditions and recrudescence cannot always be distinguished from reinfection.
      Although it was impossible to distinguish between sensitivity and RI level of
      resistance, it was concluded that chloroquine is still effective and the drug of
      choice in the area studied, while SP is a possible first line alternative.

PMID- 8287863
TI  - The 19th Kellersberger Memorial Lecture, 1993. Nerve damage, disabilities and
      rehabilitation in leprosy.

PMID- 8287865
TI  - Myocardial damage during ischaemia and reperfusion.
AB  - Reperfusion, without doubt, is the most effective way to treat the ischaemic
      myocardium. Late reperfusion may, however, cause further damage. We attempted to
      identify the nature and time-course of metabolic changes occurring during
      ischaemia followed by reperfusion either in isolated and perfused rabbit hearts
      or in coronary artery disease (CAD) patients undergoing intracoronary
      thrombolysis or aortocoronary bypass grafting. In isolated hearts, reperfusion
      after prolonged ischaemia causes exacerbation of cell damage, leading to a
      breakdown of the permeability barrier of ions as well as of larger molecules,
      such as creatine phosphokinase. As consequence, reperfusion results in a large
      increase in intracellular calcium, leading to mitochondrial calcium overload with
      subsequent damage to the mitochondrial structure and loss of the ability to
      produce adenosine triphosphate (ATP). The ultimate mediator of the membrane
      damage is not known. It has been suggested that myocardial production of oxygen
      free radicals above the neutralizing capacity of the myocytes is an important
      cause of reperfusion damage. There is evidence that prolonged ischaemia reduces
      the naturally occurring defence mechanisms of the heart against oxygen free
      radicals, particularly mitochondrial manganese superoxide dismutase, and the
      intracellular pool of reduced glutathione. Consequently, reperfusion results in
      severe oxidative damage, as evidenced by tissue accumulation and release of
      oxidized glutathione. An oxygen free radical-mediated impairment of mechanical
      function also occurs during reperfusion of the human heart. During surgical
      reperfusion of CAD patients, we observed a prolonged and sustained release of
      oxidized glutathione; the degree of oxidative stress can inversely correlated
      with recovery of mechanical and haemodynamic function.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8287864
TI  - Chromosomal aberrations and neutrophil activation induced by reperfusion in the
      ischaemic human heart.
AB  - Imperfect myocardial protection during prolonged ischaemia results in adverse
      changes during reperfusion. Clinical studies carried out during cardiac surgery
      show that: (1) Oxygen free radicals produced during reperfusion can lead to
      chromosomal damage in leukocytes. However, this effect seems to be prevented by
      the addition of allopurinol in the cardioplegic solution. (2) Polymorphonuclear
      leukocytes are directly implicated in situ in the genesis of free radicals
      responsible for reperfusion injury. (3) Pre-treatment with trimetazidine, an anti
      ischaemic drug with antioxidant properties, and addition of the drug to the
      cardioplegic solution reduced oxygen free radical damage, as shown by a reduced
      release of malondialdehyde increase and of myosin; moreover, pre-treatment with
      trimetazidine enabled patients to undergo surgery with improved left ventricular
      function.

PMID- 8287866
TI  - The mechanism of myocyte death in ischaemia.
AB  - Mechanisms of myocyte cell death in severe ischaemia may include: (1) accumulated
      metabolic products; (2) activation of membrane phospholipases; (3) formation of
      oxygen-derived free-radicals; (4) infiltration by activated neutrophils; (5)
      increased circulating catecholamines; (6) cytosolic calcium overload; (7) an
      inadequate supply of glycolytically produced ATP. The hypothesis is proposed that
      failure of glycolysis leads to inadequate control of intracellular calcium, which
      is a lethal event. This hypothesis would explain the concept that in the
      hibernating myocardium, viable zones can be detected by positron emission
      tomography of fluoro-deoxyglucose.

PMID- 8287867
TI  - Rationale for trimetazidine administration in myocardial ischaemia-reperfusion
      syndrome.
AB  - Although early reperfusion of cardiac tissue is now considered to be the only
      intervention capable of restoring the various cellular functions altered by
      ischaemia and preventing progression towards necrosis of myocardial cells,
      reperfusion is frequently accompanied by various manifestations grouped under the
      heading of reperfusion syndrome or reperfusion injury. Functional recovery is
      therefore not immediate, but usually appears after a certain delay following a
      period of contractile dysfunction (myocardial stunning) lasting for several hours
      or even days after the start of reperfusion. Characteristic reperfusion-induced
      arrhythmias are also observed. The cellular mechanisms underlying the reperfusion
      syndrome may involve cellular calcium overload, over-production of oxygen-derived
      free radicals, acidosis and/or development of an inflammatory reaction. Numerous
      pharmacological studies have been conducted over several years designed to limit
      such reperfusion injury and, consequently, prevent stunning and/or reperfusion
      induced arrhythmias. A number of experimental studies in this field have
      demonstrated that trimetazidine exerts direct anti-ischaemic effects, limiting
      calcium accumulation and acidosis, inflammation and oxygen-derived free radical
      production following reperfusion. This agent therefore appears to be particularly
      promising clinically in the treatment of reperfusion lesions, for example in
      combination with thrombolysis during the acute phase of myocardial infarction.

PMID- 8287868
TI  - Thrombolysis: state of the art.
AB  - Thrombolytic treatment and aspirin will save about 50 in 1000 patients treated
      for acute myocardial infarction, but with a risk of cerebral or other serious
      bleeding in two to three in every 1000. Early treatment (< 4 h) about halves
      mortality; the benefits decline with time but are clearly proven up to 12 h from
      onset. Benefit is best and risk least when there is ST elevation and bundle
      branch (BB) block on the initial ECG. Hypotension is not a contraindication.
      There is no clear benefit from treatment of patients with ST depression, T wave
      change or a normal ECG. Streptokinase (SK), tissue plasminogen activator (tPA) or
      APSAC are equally effective with no mortality benefit for any of the drugs. SK is
      safer, particularly in older or more hypertensive patients. tPA is reserved for
      patients who have received SK during the previous year, when high antibody titres
      may neutralize its effect on a second myocardial infarction (MI). Heparin (either
      i.v. or high dose S/Q) added to aspirin may confer some small additional benefit,
      but at the cost of significantly increased risk of bleeding. It should be
      reserved for high risk patients. Routine angioplasty is unhelpful. Investigation
      should be reserved for patients with continuing symptoms or ECG evidence of
      ischaemia, at rest or after stress testing. The benefits of thrombolysis are seen
      at all ages, in both sexes, and whatever the site of the MI. Aspirin 75-100 mg
      daily should be continued long-term.

PMID- 8287869
TI  - Free radicals, reperfusion and myocardial infarction therapy: European Myocardial
      Infarction Project--free radicals pilot study. EMIP-FR Pilot Study Group.
AB  - Reperfusion injury due to overproduction of free radicals may reduce the efficacy
      of thrombolytic therapy. Trimetazidine is an agent which could prevent or limit
      the deleterious effects of free radicals on the myocardium and could, therefore,
      improve the prognosis for patients with acute myocardial infarction (MI)
      receiving thrombolytic therapy. In this pilot study, 136 patients with suspected
      acute MI were randomized to receive either 40 mg trimetazidine as an intravenous
      (i.v.) bolus followed by an infusion of trimetazidine at 60 mg.24 h-1 for 48 h (n
      = 69) or matching placebo (n = 67). Stratification was based on the use ('T'
      stratum; n = 69) or not ('NT' stratum; n = 67) of a thrombolytic. The mean age of
      patients was 64.2 years (+/- 12.7), and the final diagnosis at discharge was
      confirmed MI in 92% of patients. No statistically significant difference was
      observed for the occurrence of major or minor adverse events. Eight patients died
      before discharge; three in the trimetazidine group and five in the placebo group.
      The observed compliance was good and the low rate of adverse events suggests that
      the study treatment can be considered safe in patients with suspected acute MI,
      either receiving thrombolytic treatment or not. The study is feasible and no
      major practical problem can be expected from this simple protocol. We started
      recruitment of patients for the large-scale mortality and morbidity trial in
      October 1992.

PMID- 8287870
TI  - Myocardial cytoprotection during percutaneous transluminal coronary angioplasty.
AB  - Transluminal coronary angioplasty (PTCA) is a well defined controlled model
      inducing regional myocardial ischaemia in man. Direct cardiac anti-ischaemic
      effects of anti-anginal drugs can be assessed by intracoronary injection of small
      doses which do not affect systemic parameters. Trimetazidine (TMZ) has recently
      been shown to improve anginal symptoms without modifying haemodynamic variables.
      A randomized, double-blind, placebo-controlled trial was conducted in 20 patients
      to study the effects of TMZ on the severity of myocardial ischaemia during PTCA
      of the left anterior descending coronary artery. Five minutes after a first
      successful dilation (D0), a control balloon inflation (D1) was performed until
      onset of ischaemic signs on both the intracoronary (i.c.) and precordial ECG. Two
      minutes later, patients received either trimetazidine 6 mg or placebo i.c.
      Another inflation (D2) was performed 5 min after D1. No differences were found
      between the two groups regarding responses in heart rate, systemic and i.c.
      pressures during the study. TMZ decreased maximum ST segment shift at D2 as
      compared to D1 (0.8 +/- 0.1 vs 1.4 +/- 0.3 mV, P = 0.023) and delayed its onset
      (46 +/- 4 vs 36 +/- 5 s, P = 0.024). TMZ also decreased maximum T wave changes
      (1.06 +/- 0.24 vs 2.19 +/- 0.3 mV, P = 0.001), and significantly reduced the area
      under the curve (AUC:mV.s-1) of the i.c. ST segment and T wave changes during
      balloon inflation (P = 0.002 and P < 0.001 respectively). Placebo had no effect
      on any of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287871
TI  - Nuclear medicine activities at the IAEA.

PMID- 8287872
TI  - Functional results of radioiodine therapy with a 300-Gy absorbed dose in Graves'
      disease.
AB  - The aim of this study was to assess the results of high-dose radioiodine therapy
      given to 43 patients with recurrent hyperthyroidism due to Graves' disease
      between 1986 and 1992. We chose an intrathyroidal absorbed dose of 300 Gy and
      determined the applied activity individually, which ranged from 240 to 3120 MBq
      with a median of 752 MBq. Hyperthyroidism was eliminated in 86% of cases after 3
      months and in 100% after 12 months. No patient required a second radioiodine
      treatment. The incidence of hypothyroidism was 63% after 3 months and 93% after
      18 months. Neither the pretherapeutic thyroid-stimulating immunoglobulin level
      nor the degree of co-existing endocrine ophthalmopathy was correlated with the
      time at which hypothyroidism developed. Patients with previous radioiodine
      therapy developed hypothyroidism earlier than patients with previous thyroid
      surgery. The results show that ablative radioiodine therapy with a 300-Gy
      absorbed dose is a very effective treatment of hyperthyroidism in Graves'
      disease, but it should be restricted to patients with recurrent hyperthyroidism
      combined with severe co-existing disorders or episodes of unfavourable reactions
      to antithyroid drugs.

PMID- 8287873
TI  - Long-term results of two schedules of radioiodine treatment for toxic
      multinodular goitre.
AB  - The long-term effects of two schedules of radioiodine therapy in patients with
      toxic multinodular goitre were evaluated. Forty-five patients (group A) were
      treated with low doses and 58 patients (group B) with calculated doses adjusted
      for thyroid weight (1.85-3.70 MBq/g) and radioactive iodine uptake. Follow-up
      (mean +/- SEM) was 4.3 +/- 0.2 years and 5.2 +/- 0.3 years, respectively (P >
      0.1). At the end of follow-up, hyperthyroidism was successfully reversed in 73%
      (group A) and 88% (group B). In each group, hypothyroidism was present in 7%. The
      total dose per gram of thyroid tissue was not significantly different in groups A
      and B (2.1 +/- 0.2 vs 2.7 +/- 0.2 MBq/g). However, for patients treated with
      calculated doses the number of 131I administrations was significantly lower (1.3
      +/- 0.1) than for patients treated with low doses (2.2 +/- 0.2), and the
      percentage of patients who were adequately treated with a single dose was more
      than twice as high (66% in group B versus 27% in group A). Euthyroidism was
      reached within a significantly shorter time after treatment with calculated doses
      (median time 0.6 years in group B vs 1.5 years in group A; life table analysis).
      It is concluded that radioiodine is an effective treatment for toxic multinodular
      goitre with a low risk of post-treatment hypothyroidism and that calculated
      (higher) doses appear to be preferable to low doses.

PMID- 8287874
TI  - The value of bone scintigraphy, bone marrow scintigraphy and fast spin-echo
      magnetic resonance imaging in staging of patients with malignant solid tumours: a
      prospective study.
AB  - The purpose of this prospective study was to define the value of bone
      scintigraphy (BS), bone marrow scintigraphy (BMS) and the new fast spin-echo
      (FSE) magnetic resonance imaging (MRI) sequences in screening for bone metastases
      in patients with solid malignant tumours. It was our particular interest to
      classify patients into a group with and a group without bone metastases, and not
      only to compare the absolute number of metastases detected by each method. Thirty
      two patients were examined using technetium-99m dicarboxy propane diphosphonate
      bone scintigraphy, 99Tc-labelled monoclonal anti-granulocyte antibodies for bone
      marrow scintigraphy and 1.5 T MRI using T1-weighted and FSE T2-weighted
      sequences. Against a reference standard obtained by re-evaluation of all clinical
      and imaging data 1 year after prospective BS, BMS and MRI had been performed, the
      three imaging modalities were falsely positive in two, eight and two cases and
      falsely negative in zero and four cases, respectively. BMS was falsely positive
      in eight patients because of vertebral marrow degeneration which caused
      photopenic defects which could not be differentiated from metastases. MRI showed
      these lesions to unequivocally contain fat. BMS and MRI were falsely negative in
      four cases because of the limited field of examination. In our study the key
      factor in classifying a patient as bone M1 or M0 was the possibility of surveying
      the entire skeleton, as is the case in BS, and not that MRI had a higher
      sensitivity compared to BS when analysis was on a lesion-by-lesion
      basis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287875
TI  - Utility of thallium-201 and iodine-123 metaiodobenzylguanidine in the
      scintigraphic detection of neuroendocrine neoplasia.
AB  - Metaiodobenzylguanidine (MIBG) is a specific marker for neuroendocrine tumours,
      such as phaeochromocytoma, neuroblastoma, medullary thyroid cancer (MTC) and
      paraganglioma, but it suffers in some cases (especially in MTC) from a lack of
      sensitivity. Thallium is a well-known marker of cellularity with a great
      sensitivity and a lack of specificity. In order to determine whether the
      association of these two markers is able to improve the detection of
      neuroendocrine lesions, 137 scintigraphic examinations using MIBG and thallium
      were performed in 101 patients referred for suspicion or follow-up of
      neuroendocrine tumours. Thallium chloride was first injected (1 MBq/kg), images
      being acquired about 20 min after injection; 123I-MIBG (4 MBq/kg) was then
      injected and images acquired 5 and 24 h later. In patients with phaeochromocytoma
      or neuroblastoma, thallium scintigraphy appeared of little help since no tumoural
      site was discovered by thallium accumulation alone. In contrast, thallium
      examination seemed of interest in the detection of paraganglioma and MTC, the
      association of the two radiopharmaceuticals increasing the number of detected
      sites.

PMID- 8287876
TI  - Use of immunoscintigraphy in the diagnosis of fever of unknown origin.
AB  - Fever of unknown origin (FUO) has been defined as an elevation in temperature (38
      degrees C) for at least 2-3 weeks despite intensive investigation. The value of
      immunoscintigraphy with the technetium-99m-labelled anti-granulocyte antibody
      anti-NCA-95 (BW 250/183, IgG1) was studied retrospectively in 34 consecutive
      patients with FUO. Every effort was made to confirm a diagnosis, including
      methods such as ultrasonography, computed tomography, magnetic resonance imaging,
      bacteriological tests, surgical intervention and clinical follow-up. In 58.8% of
      the patients, an infectious cause for the fever was found, in 30.2% of the
      patients, a benign or malignant haematological disease, pancreatitis or
      thyrotoxicosis was found. No cause for fever could be found in 11%. The overall
      diagnostic sensitivity and specificity of immunoscintigraphy for infection were
      40% and 92% respectively. The positive predictive value was calculated to be 88%
      and the negative predictive value was calculated to be 52%. False-negative scans
      were especially noted in patients with endocarditis, pneumonia and small brain
      abscesses, where the lesions did not exceed a diameter of 0.5 cm. If patients
      with endocarditis were excluded, the imaging sensitivity and specificity were
      increased to 57% and 95%. This study demonstrates that 99mTc-anti-NCA-95 scanning
      is able to localize infectious causes of FUO, other than endocarditis.

PMID- 8287877
TI  - Influence of intravenously administered lidocaine on cerebral blood flow in a
      baboon model standardized under controlled general anaesthesia using single
      photon emission tomography and technetium-99m hexamethylpropylene amine oxime.
AB  - The baboon under general anaesthesia as a model to assess drug-induced cerebral
      blood flow changes (delta CBF) using single-photon emission tomography (SPET)
      offers great in vivo possibilities but has to comply with demands on control of
      anaesthesia-related influencing factors, such as PaCO2 changes. The model sought
      in this study and described here allows control of PaCO2, in the baboon under
      thiopentone anaesthesia by ventilation, and was evaluated for the functional
      dependence of delta CBF vs delta PaCO2, using SPET technetium-99m
      hexamethylpropylene amine oxime (HMPAO) and the split-dose method together with
      controlled ventilation. During the experiment the model was validated for normal
      reactivity to PaCO2 changes, and subsequently applied to investigate the
      mechanisms (still uncertain) of CBF increase known to follow administration of
      the local anaesthetic lidocaine. Six baboons received 6 mg/kg lidocaine
      intravenously. CBF was measured between two consecutive SPET acquisitions (split
      dose method) respectively relating to HM-PAO distributions in the brain before
      and after the injection of lidocaine. Meanwhile the animals were maintained at
      constant respiratory rate and volume. The results indicate that the correlation
      between delta CBF and the ensuing fall in PaCO2 deviated from the baseline
      pattern from the model and confirmed a cerebrovascular contribution to the
      lidocaine-induced CBF increase. This agreed well with mean and systolic blood
      pressure changes and heart rate.

PMID- 8287878
TI  - Three-dimensional cold spot volume rendering.
AB  - Three-dimensional volume rendering enhances the perception of radiopharmaceutical
      distribution within organs. Formerly, a maximum activity projection method was
      developed for hot spot rendering, which increases the contrast between hot spots
      and normal tissue. This method can only render cold spots at organ edges; a
      decrease in uptake within organs is not displayed. In this contribution, it is
      shown that the projection technique developed for hot spot imaging also can be
      used for cold spot rendering after suitable transformation of the tomographic
      data format.

PMID- 8287879
TI  - Regional uptake of iodine-125-metaiodobenzylguanidine in the rat heart.
AB  - Regional uptake of iodine-125-metaiodobenzylguanidine ([125I]MIBG) was evaluated
      in normal (n = 12) and reserpinized (n = 12) rat hearts. At 15 min and 1, 3 and 6
      h after injection of [125I]MIBG, tissue activities were calculated for the right
      ventricular myocardium (RV), the whole left ventricular myocardium (whole LV),
      the epicardial layer of the left ventricular myocardium (Ep LV), the endocardial
      layer of the left ventricular myocardium (En LV), the basal segment of the left
      ventricular myocardium and the apical segment of the left ventricular myocardium.
      The uptake of [125I]MIBG at 6 h after injection in the normal rat heart was
      higher in RV than in whole LV (0.45 +/- 0.09% vs 0.30 +/- 0.06% kg dose/g), and
      in Ep LV than in En LV (0.32 +/- 0.07% vs 0.25 +/- 0.05%). In the reserpinized
      rat heart, the difference in the uptake between Ep LV and En LV was smaller. This
      suggests that the difference in the regional [125I]MIBG uptake might reflect
      different intravesicular uptake in the layers of the heart. To our knowledge, the
      low uptake in the endocardial layer was a new finding which seems to indicate a
      difference in innervation between the epicardial and endocardial layers of the
      left ventricle in the rat heart. Autoradiographic study also showed the low
      uptake of [125I]MIBG in the endocardial layer, while homogeneous perfusion was
      observed with thallium-201, supporting the tissue uptake study. Thus, the
      endocardial and epicardial layers of the left ventricle in the rat heart were
      considered to be differently innervated.

PMID- 8287880
TI  - Parametric phase display for biventricular function from gated cardiac blood pool
      single-photon emission tomography.
AB  - Complete assessment of biventricular function from planar ECG-gated cardiac blood
      pool studies has been limited because of the overlap of adjacent activity
      containing structures. Theoretically, single-photon emission tomography (SPET)
      can be used to comprehensively evaluate both ventricles by isolating them from
      surrounding anatomy. However, an enormous amount of parametric data is generated
      from gated SPET studies, and much of it is diagnostically irrelevant for
      ventricular wall motion analysis. To compress this information to a more easily
      interpretable format, a two-dimensional parametric display has been developed.
      Fourier analysis of short-axis tomograms from a gated cardiac blood pool SPET
      study generates three-dimensional, first-harmonic phase data. Circumferential
      profile data from the parametric tomograms of the right and left ventricle are
      mapped onto a two-dimensional polar display. This method is demonstrated in a
      normal patient and in three patients with abnormal ventricular contraction
      patterns and appears to have potential application for the analysis and
      characterization of biventricular wall motion.

PMID- 8287881
TI  - Radiation synovectomy revisited.
AB  - Radiation synovectomy is a potential weapon in the therapeutic armamentarium of
      nuclear medicine. It is an attractive alternative to surgical or chemical
      synovectomy for the treatment of rheumatoid arthritis. In this article the
      clinical results obtained with radiation synovectomy from the 1950s through 1992
      are summarized and reviewed. Even after taking into account the paucity of well
      controlled trials and rigorous clinical follow-up, it is clear that radiation
      synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis.
      However, the procedure is not widely used because of concerns about leakage of
      radioactivity from the treated joint, and the resulting high doses that can be
      delivered to nontarget organs. New approaches to the preparation of radiolabeled
      particles for use in radiation synovectomy promise to minimize this leakage and
      thus allow the full potential of this important radiotherapy to be realized.

PMID- 8287882
TI  - Radioimmunoscintigraphy with technetium-99m labelled monoclonal antibody, 1A3, in
      colorectal cancer.

PMID- 8287883
TI  - Technetium-99m DTPA in CSF.

PMID- 8287884
TI  - Neoadjuvant therapy in prostate cancer--is it of any use?
AB  - Since 1941, when the androgen dependency of prostatic carcinoma was described
      first, the question whether neoadjuvant hormone manipulation enhances surgical
      curability has been of actual importance. With the availability of reversible
      luteinizing hormone-releasing hormone analogues and non-steroidal antiandrogens,
      interest in preoperative hormonal manipulation has recently been reinnovated. An
      overview of the published, sometimes conflicting clinical and pathological
      studies evaluating the value of neoadjuvant hormone manipulation is given. We
      conclude that further well-controlled clinical investigations comparing
      downstaging and downgrading percentages, percentages of local control and
      survival are needed to prove the benefit of neoadjuvant treatment in patients
      with locally confined prostatic carcinoma.

PMID- 8287885
TI  - New prognostic factors in prostatic carcinoma.

PMID- 8287886
TI  - Histopathological changes in androgen-deprived localized prostatic cancer. A
      study in total prostatectomy specimens.
AB  - Androgen deprivation with triptorelin treatment prior to total prostatectomy gave
      the opportunity of studying consequent morphological changes in the surgical
      specimens from 38 men with localized prostatic cancer. Multiple core-needle
      biopsies were taken prior to treatment and compared to the step-sectioned
      surgical specimens. The histological changes in the prostate following androgen
      deprivation include glandular atrophy, nuclear pyknosis, cytoplasmic vacuolation,
      squamous metaplasia and an increase in the relative amount of stroma. None of
      these changes could be correlated to pretreatment tumour grade, nor to the volume
      of the residual tumour. A positive correlation was found between tumour grade
      prior to therapy and volume of residual tumour after treatment. The treatment was
      not associated with downgrading of the malignancy. On the contrary, in 16% of the
      cases, foci of a higher grade were found in the surgical specimens compared to
      the pretreatment core-needle biopsies.

PMID- 8287887
TI  - Total androgen suppression: experience from the Scandinavian Prostatic Cancer
      Group Study No. 2.
AB  - A total of 294 patients with metastatic prostatic cancer were randomized
      prospectively in a Scandinavian multicenter study to either bilateral
      orchiectomy+placebo or orchiectomy+cyproterone acetate (CPA). The study was
      double blind. Patients with histologically verified prostatic cancer, with
      diagnosed skeletal metastases on X-ray or bone scintigrams and histological grade
      1 and 2 were included: T0-4NXM1G1-2. 273 evaluable patients were followed either
      to progression, death or for a period of 3 years. 195 of these patients showed
      disease progression during the 3-year treatment period, 29 had stable disease and
      49 patients experienced disease remission. The Kaplan-Meier analyses showed that
      time to progression as well as time to death for patients treated with
      castration+placebo are identical to that for patients treated with
      castration+PCA. Total androgen blockade with this antiandrogen was not superior
      to the standard orchiectomy treatment.

PMID- 8287888
TI  - Do seminal or prostatic secretions play a role in local recurrence after radical
      prostatectomy for localized prostate cancer?
AB  - Neoplastic cellular contamination of the surgical bed may be responsible for late
      local failure after radical prostatectomy. Cytology analysis of the seminal and
      prostatic fluid collected intraoperatively was undertaken in 30 patients.
      Neoplastic cells were found in 2 patients both with seminal vesicle involvement.
      Although it is difficult to admit that tumor spillage during surgery would be a
      major cause of local recurrence, the presence of tumor cells in the ejaculate may
      be diagnostic of seminal vesicle invasion. All patients with pathologic stage T2
      had a negative cytologic finding.

PMID- 8287889
TI  - Prostatic 'capsule'--a comparative study of histological and ultrasonic
      appearances.
AB  - The histological and transrectal ultrasound (TRUS) appearances at corresponding
      sites of the periphery of the prostate gland have been compared in 30 benign and
      27 malignant glands taken at autopsy. In the benign series, the histological
      capsule was frequently absent and correlated poorly with the consistent TRUS
      findings of a regular, well-defined 'ultrasonic capsule'. It is concluded that
      'the capsule' should be replaced as a tumour-staging landmark by a more realistic
      terminology. Carcinoma may be described as intra- or extra-prostatic, or confined
      or unconfined with respect to the gland. In the malignant glands, there was no
      correlation between morphologically unconfined cancers and irregular or absent
      ultrasound 'capsule' when corresponding areas were compared. This disparity must
      contribute to an underestimation of tumour extent with TRUS.

PMID- 8287890
TI  - Quantitative analysis of bone metastasis in prostate cancer.
AB  - A new method of quantitative analysis of bone metastasis in prostate cancer is
      described. By using a variance-dependent filter and a smoothing filter, the
      increased uptake lesions were distinctly demonstrated on the bone scintigraphy.
      The images were divided into several areas and analyzed. These procedures
      resulted in a clear identification of the metastatic lesions. Repeated
      measurements of the metastatic areas from the same scintigrams disclosed a high
      reproducibility. This method appears to be highly consistent and clinically
      applicable.

PMID- 8287891
TI  - New treatment modality for penile urethral strictures using a self-expanding and
      self-retaining coil stent: UroCoil. Follow-up of 16 months after removal of the
      stent.
AB  - Twelve penile urethral strictures which were managed in the past (2-21 years) by
      dilatations, urethrotomies, or by urethroplasty, were treated by an insertion of
      a temporary but long-term metallic coil stent. In 9 cases, the stent was left in
      place 6-9 months; in 3 cases, the stent is still in place. During the time the
      stent was inside, 4 patients who were sexually active before insertion of the
      stent were able to continue sexual activity. During a mean follow-up time of 16
      months (range 4-24 months) after the removal of the stent, in only 1 case did the
      stricture recur. At present, this new internal device is the only one which can
      stent the penile part of the urethra temporarily without interfering with the
      sexual activity of the patient, and without causing pain or the risk of urethral
      perforation.

PMID- 8287892
TI  - Management of primary obstructive megaureter without reflux in neonates.
AB  - Systematic antenatal ultrasonography has significantly altered the conditions of
      diagnosis of megaureters. Pediatric urologists are now confronted with a large
      group of neonates with asymptomatic megaureter. Furthermore, reports of
      spontaneous resolution of primary megaureter without reflux have become common.
      We were confronted with 59 renal units in 48 neonates. We postulated that primary
      megaureter represented a significant obstructive uropathy when the kidney
      exhibited stasis and large pelvic and caliceal dilatations. So, 35 ureters were
      operated on initially. The other 24 cases were managed conservatively but among
      these patients, 11 ureters were operated on secondarily 7-29 months after the
      diagnosis because they were unchanged [6] or worsened [5]. 13 ureters are
      currently without treatment: 7 total regressions and 6 incomplete regressions
      with persistent mild pelvic dilatation. The results of reimplantation, early or
      delayed, have been excellent (1 postoperative necrosis reoperated, 1 secondary
      reimplantation, 2 persistent mild dilatations). Relief of obstruction without
      reflux was obtained in 36/39 long-term follow-up cases (92%). There is a
      disagreement about the relative merits of various modalities in the assessment of
      ureteral obstruction and impairment of renal function. Therefore, we chose to use
      essentially intravenous pyelography (IVP) and to operate initially when there was
      a delayed appearance of the contrast agent, a massive dilatation and delayed
      drainage from the ureter into the bladder. This attitude is open to question but
      no more illogical than waiting for impairment of renal function to decide on
      surgery.

PMID- 8287893
TI  - 5 alpha-reductase deficiency: human and animal models.
AB  - The syndrome of male pseudohermaphroditism secondary to 5 alpha-reductase
      deficiency is reviewed, as are hormonal evaluation and tissue studies documenting
      the enzyme deficiency. These studies reveal that the 5 alpha-metabolite
      dihydrotestosterone is essential for differentiation of the external genitalia
      and prostate. Studies of male rat fetuses treated with 5 alpha-reductase
      inhibitors during the critical period of sexual differentiation in utero reveal
      incomplete masculinization of the external genitalia and impaired prostate growth
      and development. Thus, conclusive evidence is provided for the hypothesis that 5
      alpha-reductase activity and dihydrotestosterone formation are essential for
      normal differentiation of the male external genitalia and the prostate.

PMID- 8287894
TI  - Chronic antidepressant drug treatment attenuates motor-suppressant effects of
      apomorphine without changing [3H]GBR 12935 binding.
AB  - The effects of chronic administration (28 days s.c. via osmotic minipumps) of the
      antidepressants phenelzine sulphate, desipramine hydrochloride and clomipramine
      hydrochloride (each at 10 mg/kg per day) on dopamine function have been measured
      in rats. Both phenelzine and desipramine attenuated the suppression of locomotor
      activity induced by apomorphine hydrochloride (0.05 mg/kg s.c. 15 min).
      Clomipramine did not affect the behavioural response to apomorphine. Analyses of
      brain tissue from these animals using the radioligand [3H]GBR 12935 revealed that
      there were no changes in dopamine uptake site density or affinity following the
      administration of phenelzine, desipramine or clomipramine. Analyses of brain
      monoamine oxidase activity and tricyclic levels were used to confirm the efficacy
      of the drug administration protocol. These data indicate that changes in dopamine
      uptake site density do not mediate antidepressant-induced changes in behavioural
      responses to apomorphine.

PMID- 8287895
TI  - Endothelin-1 enhances vasoconstrictor responses to exogenously administered and
      neurogenically released ATP in rabbit isolated perfused arteries.
AB  - Vasoconstrictor responses to ATP were enhanced in a concentration-dependent
      manner by endothelin-1 (0.1-1 nM) in isolated perfused segments of rabbit ear
      artery. Higher concentrations of endothelin-1 (3-10 nM) also enhanced
      vasoconstrictor responses to ATP. The enhancement of ATP responses by endothelin
      1 (0.1-10 nM) was not affected by nicardipine (10 nM). The ATP-mediated component
      of the vasoconstrictor response to perivascular nerve stimulation in the rabbit
      jejunal artery was enhanced by endothelin-1 to a similar extent as that to
      exogenously administered ATP. The enhancement of vasoconstrictor responses to
      neurogenic ATP was also not affected by nicardipine.

PMID- 8287896
TI  - CD-832, a new dihydropyridine derivative with both nitrate-like and Ca2+ channel
      antagonist vasodilator activities.
AB  - We investigated the effects of CD-832 ((4R)-(-)-2-(nicotinoylamino)ethyl 3
      nitroxypropyl 1,4-dihydro-2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine
      dicarboxylate), a new dihydropyridine derivative with nitrate ester, on
      contraction and relaxation responses induced by various vasoactive agents in
      rabbit aorta. CD-832 potently inhibited the specific binding of [3H](+)-PN200-110
      to rat brain membranes. The IC50 values for [3](+)-PN200-110 binding were 2.8 nM
      and 4.9 nM in CD-832 and nifedipine, respectively. CD-832 (10(-8) to 10(-5) M),
      diltiazem (10(-8) to 10(-5) M) and benidipine (10(-8) to 10(-5) M) inhibited the
      64 mM KCl-induced contraction of the aortic strips in a concentration-dependent
      manner. Neither nitroglycerin (10(-8) to 10(-5) M) nor nicorandil (10(-8) to 10(
      5) M) affected the 64 mM KCl-induced contraction in rabbit aorta. CD-832 (10(-8)
      to 10(-5) M), nitroglycerin (10(-8) to 10(-5) M) and nicorandil (10(-5) M) had no
      effect on norepinephrine-induced contraction in rabbit aorta. Nitroglycerin (10(
      5) M), atrial natriuretic peptide (10(-8) M), nicorandil (10(-5) M) and CD-832
      (10(-7) to 10(-5) M) augmented the isoproterenol-induced relaxation responses of
      rabbit aorta precontracted with endothelin-1 (1 x 10(-7) to 2 x 10(-7) M). The
      effects of nitroglycerin (10(-5) M), nicorandil (10(-5) M) and CD-832 (10(-5) M)
      on isoproterenol-induced relaxation responses were antagonized by treatment with
      methylene blue (10(-5) M) and oxyhemoglobin (10(-5) M).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8287897
TI  - Antitussive effects of naltrindole, a selective delta-opioid receptor antagonist,
      in mice and rats.
AB  - The effects of naltrindole, a selective delta-opioid receptor antagonist, on the
      capsaicin-induced cough reflex in mice and rats were studied. Intraperitoneal
      administration of naltrindole decreased the number of coughs both in mice and
      rats dose dependently. The cough-depressant effects reached a peak 15 min after
      the administration of naltrindole and lasted more than 120 min. Pretreatment with
      [D-Pen2,D-Pen5]enkephalin, a selective delta-opioid receptor agonist, partially
      but significantly reduced the antitussive effect of naltrindole. Blockade of
      kappa-opioid receptors by pretreatment with nor-binaltorphimine also partially
      antagonized the antitussive effect of naltrindole. However, the antitussive
      effect of naltrindole was not antagonized by beta-funaltrexamine, a selective mu
      opioid receptor antagonist. Thus, it is possible that the antitussive effect of
      naltrindole may be mediated, in part, by kappa-opioid receptors. The present
      results provide evidence for the development of delta-opioid antagonists,
      especially naltrindole, for use as antitussive drugs.

PMID- 8287898
TI  - Delta-opioid receptor antagonists attenuate motor activity induced by amphetamine
      but not cocaine.
AB  - Naloxone and naltrindole attenuate the locomotor response to amphetamine,
      implicating delta-opioid receptors in the opioid-antagonist/amphetamine
      interaction. To determine the role of delta-opioid receptor subtypes in this
      phenomenon, rats were pretreated with the following selective antagonists
      administered intracisternally: naltrindole, [D-Ala2,Leu5,Cys6]enkephalin (DALCE,
      delta 1 receptor selective), naltrindole-5'-isothiocyanate (delta 2 receptor
      selective). Cumulative dose-response curves to amphetamine were constructed
      (saline, 0.1, 0.4, 1.6 and 6.4 mg/kg s.c.), with injections every 30 min.
      Naltrindole was also tested against cumulative doses of cocaine (saline, 3.0, 10,
      30 and 56 mg/kg i.p.). Gross and fine motor activity were recorded for 20 min,
      commencing 10 min postinjection. Amphetamine and cocaine dose dependently
      increased both gross and fine movements. Naltrindole (10 micrograms) attenuated
      the gross but not fine activity response to amphetamine, but 10 or 30 micrograms
      failed to influence the response to cocaine. Naltrindole-5'-isothiocyanate (30
      micrograms) attenuated slightly but significantly the gross activity response to
      amphetamine, whereas DALCE (30 micrograms) was without effect. However, a
      combination of 10 micrograms each of DALCE and naltrindole-5'-isothiocyanate
      markedly attenuated the amphetamine-induced increases in gross movements without
      altering fine activity. These data provide further evidence for the involvement
      of delta-opioid receptors in the modulation of behavioral effects of amphetamine;
      both delta 1- and delta 2-opioid receptors appear to play a role. The
      differential effects of opioid antagonists on locomotor activity stimulated by
      amphetamine and cocaine suggests differences in the mechanism of action of these
      drugs not previously appreciated.

PMID- 8287899
TI  - Topical capsaicin administration protects against trinitrobenzene sulfonic acid
      induced colitis in the rat.
AB  - We used the [3H]resiniferatoxin binding assay to demonstrate for the first time
      the existence of vanilloid receptors in the rat colon and to explore their
      expression during trinitrobenzene sulfonic acid-induced colitis. Membranes
      obtained from control colon bound [3H]resiniferatoxin with an affinity of 3 nM;
      the receptor density was 450 fmol/mg protein or 9 fmol/mg wet weight. Capsaicin
      and capsazepine, a competitive antagonist of capsaicin, inhibited specific
      resiniferatoxin binding with Ki values of 3 microM and 0.1 microM, respectively.
      Trinitrobenzene sulfonic acid induced a very rapid ulceration in the colon: 1 h
      after treatment 90% of the colon showed ulcerative damage. Coadministration of
      640 microM capsaicin diminished the ulcerative effect of trinitrobenzene sulfonic
      acid to 64% when examined 1 h after trinitrobenzene sulfonic acid challenge;
      however, this protective action was lost 23 h later. Colon samples obtained 4 h,
      24 h, and 1 week after trinitrobenzene sulfonic acid challenge bound
      resiniferatoxin, capsaicin, and capsazepine with affinities similar to those of
      control samples. The receptor density remained at an essentially constant level
      when expressed in fmol/mg protein but, in keeping with the increased wet weights,
      showed a reduction when expressed in fmol/mg wet weight. We conclude that acute
      capsaicin administration protects against the ulcerative action of
      trinitrobenzene sulfonic acid, most likely via the release of protective
      neuropeptides from capsaicin-sensitive nerve endings. The loss of this protective
      action is presumably due to a depletion of the protective neuropeptides rather
      than to a loss of vanilloid (capsaicin) receptors.

PMID- 8287900
TI  - Effect of vascular smooth muscle relaxants on the protein kinase C-mediated
      contraction in the rat pulmonary artery.
AB  - In the rat pulmonary artery, phorbol 12,13-dibutyrate induces a contraction due
      to the activation of the protein kinase C. We investigated the sensitivity of
      this protein kinase C-mediated contraction to a variety of vascular smooth muscle
      relaxants. Pretreatment of rat pulmonary artery with relaxant compounds altered
      the subsequent concentration-response curve to phorbol 12,13-dibutyrate (0.05-2
      microM) in a variable manner. Isoprenaline (0.1-10 microM), nifedipine (0.01-1
      microM) and cromakalim (0.1-10 microM) had no effect, whereas vasoactive
      intestinal peptide (VIP, 1-10 nM), forskolin (0.1-2 microM), theophylline (0.1
      2.5 mM), 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO 20-1724, 2-20
      microM), dipyridamole (10-100 microM), 8 bromo-cyclic GMP (8-br-cGMP, 5-500
      microM) and dibutyryl cyclic AMP (db-cAMP, 100-500 microM) shifted the
      concentration-response curve to phorbol 12,13-dibutyrate to the right and
      decreased the maximal response. When cumulative concentrations of relaxants were
      applied on the plateau of the contraction induced by 0.2 or 2 microM phorbol
      12,13-dibutyrate, again, isoprenaline, nifedipine and cromakalim failed to
      decrease the protein kinase C-mediated contraction, whereas the other agents
      produced concentration-dependent relaxation. From their inhibitory effect on the
      0.2 microM phorbol 12,13-dibutyrate-induced contraction, the rank order of
      potency of these relaxants was: VIP >> forskolin > RO 20-1724 > 8-br-cGMP >
      theophylline > dipyridamole > db-cAMP. In chemically (beta escin) skinned
      preparations, cGMP (5-500 microM) and cAMP (50-1000 microM) antagonized in a
      concentration dependent manner the contraction induced by phorbol 12,13
      dibutyrate at constant Ca2+ concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287901
TI  - Differences between endothelin receptors mediating contraction of guinea-pig
      aorta and pig coronary artery.
AB  - Endothelin receptors mediating contraction were characterized and compared in
      rings from guinea-pig thoracic aorta and pig left circumflex coronary artery. In
      guinea-pig aorta, the following rank order of agonist potencies was found (mean
      EC50 value, nM): endothelin-1 (5.0) = endothelin-2 (5.5) > vasoactive intestinal
      contractor (VIC; 11.0) > sarafotoxin S6b (39.8) > [Ala3,11]endothelin-1 (121) >
      sarafotoxin S6a (> 150) > endothelin-3 (> 500). [Ala1,3,11,15] Endothelin-1,
      endothelin-(16-21), sarafotoxin S6c and sarafotoxin S6d were neither agonists nor
      antagonists at concentrations up to 1, 10, 3 and 1 microM, respectively. Cyclo-(D
      Trp-D-Asp-Pro-D-Val-Leu) (BQ-123; 0.1-1 microM) behaved as a competitive
      antagonist of endothelin-1 (pA2 7.4 +/- 0.1, slope factor 0.91 +/- 0.17, n = 4).
      In pig coronary artery, all endothelins and sarafotoxins were agonists, except
      for endothelin-(16-21). Sarafotoxin S6c, [Lys4]sarafotoxin S6c, [Nle6]sarafotoxin
      S6c and [Ala1,3,11,15]endothelin-1 acted as partial agonists (Emax about 40% of
      that of endothelin-1). The rank order of agonist potencies was: sarafotoxin S6c
      (1.5) = [Lys4]sarafotoxin S6c (1.5) > [Nle6]sarafotoxin S6c (6.7) > or =
      sarafotoxin S6a (7.5) > or = endothelin-1 (12.6) > or = sarafotoxin S6b (14.8) >
      or = VIC (18.3) = endothelin-2 (19.3) > or = [Ala1,3,11,15]endothelin-1 (41.7) >
      or = [Ala3,11]endothelin-1 (55.2) > endothelin-3 (96.8) > sarafotoxin S6d (>
      200). Endothelin-(16-21) was neither agonist nor antagonist at 10 microM. The
      concentration-response curves of endothelin-3 and sarafotoxin S6a were biphasic,
      consisting of a higher sensitivity (40-45% of the total effect) and a lower
      sensitivity component. BQ-123 (0.1-1 microM) did not alter the concentration
      response curve of endothelin-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287902
TI  - The mesolimbic dopamine-activating properties of ethanol are antagonized by
      mecamylamine.
AB  - It has been suggested that ethanol may interact with the central nicotinic
      acetylcholine receptor, thus providing a basis for the often observed high
      consumption of both ethanol and nicotine. In the present in vivo microdialysis
      study, ethanol (2.5 g/kg) moderately increased dopamine overflow in the rat
      nucleus accumbens. The central nicotinic acetylcholine receptor antagonist
      mecamylamine totally counteracted this effect in a dose (1.0 mg/kg) that did not
      alter dopamine overflow per se. Ethanol also increased the overflow of
      dihydroxyphenylacetic acid and homovanillic acid, but this effect was not altered
      by mecamylamine (1.0 mg/kg). Furthermore, the ethanol-induced enhancement of 3,4
      dihydroxyphenylalanine accumulation in the mesolimbic dopamine terminal area
      after NSD 1015 (an inhibitor of l-aromatic amino acid decarboxylase) was
      completely antagonized by mecamylamine in doses (3.0 and 6.0 mg/kg) that exerted
      no effects per se. Neither ethanol nor mecamylamine changed the catecholamine
      synthesis rate in the striatum or the cerebral cortex. These results provide
      further evidence that ethanol-induced activation of the mesolimbic dopamine
      system (increased dopamine synthesis and release) may be mediated via stimulation
      of central nicotinic acetylcholine receptors. It is suggested that antagonists of
      central nicotinic acetylcholine receptors may be useful in the treatment of
      alcoholism.

PMID- 8287903
TI  - Cocaine constricts immature cerebral arterioles by a local anesthetic mechanism.
AB  - The effect of cocaine on cerebral arterioles was determined in newborn pigs and
      the mechanism of action was examined in terms of its local anesthetic and
      sympathomimetic properties. Forty-three newborn piglets were anesthetized,
      equipped with a closed cranial window, and the diameter of pial arterioles was
      measured by intravital microscopy. Increasing concentrations of cocaine (10(-7) M
      to 10(-3) M) applied onto the cortical surface resulted in a dose-dependent
      decrease in arteriolar diameter. Coadministration with phentolamine, an alpha
      adrenoceptor antagonist, did not inhibit the contractile response to cocaine even
      though phentolamine blocked the constriction to topically applied norepinephrine.
      In contrast, coadministration of either tetrodotoxin (Na+ channel blocker),
      charybdotoxin (K+ channel blocker), or quinacrine (phospholipase A2 inhibitor),
      or pretreatment with indomethacin (cyclooxygenase inhibitor) attenuated
      vasoconstriction induced by cocaine. Topically applied lidocaine (10(-7) M to 10(
      3) M), a local anesthetic without sympathomimetic properties, caused a dose
      dependent constriction similar to cocaine, whereas topically applied nomifensine
      and desipramine (each 10(-7) M to 10(-3) M), inhibitors of dopamine and
      norepinephrine re-uptake, respectively, did not constrict cerebral arterioles.
      These results indicate that cocaine constricts cerebral arterioles by its local
      anesthetic properties rather than its sympathomimetic properties. The mechanism
      appears to involve an alteration in the flux of Na+ or K+ or prostanoid
      metabolism.

PMID- 8287904
TI  - Quantitative autoradiography of 5-HT1E binding sites in rodent brains: effect of
      lesion of serotonergic neurones.
AB  - Binding sites corresponding to 5-HT1E receptors were labelled in mouse, rat, and
      guinea-pig brains by using [3H]5-hydroxytryptamine ([3H]5-HT) in the presence of
      5-carboxamidotryptamine (5-CT) (0.1 microM), and their distribution within the
      brain was studied by quantitative autoradiography. The results obtained with
      mouse brain show that 5-HT1E binding sites are particularly present in the
      cortex, caudate-putamen and claustrum, where they showed the highest density.
      Lower densities were measured in other regions. Saturation experiments showed
      that the affinity of [3H]5-HT for 5-HT1E binding sites (nanomolar range) was very
      similar in the different structures. The distribution of 5-HT1E binding sites was
      similar in rat and guinea-pig brains. In rat brain, selective lesioning of
      serotonergic fibres by intracerebroventricular injection of 5,7
      dihydroxytryptamine (5,7-DHT), a specific 5-HT neurotoxin, did not affect the
      density of 5-HT1E binding, indicating that these receptors are mainly localized
      on non-serotonergic neurones.

PMID- 8287905
TI  - Voltage-dependent modulation of L-type Ca2+ current by manidipine in guinea-pig
      heart cells.
AB  - Effects of manidipine, a dihydropyridine derivative, on L-type Ca2+ currents were
      examined in guinea-pig ventricular cells, using the whole-cell patch-clamp
      method. At a holding potential of -37 mV, manidipine decreased the Ca2+ current
      at concentrations above 0.1 nM, and abolished it at 100 nM (IC50 = 2.6 nM). At a
      holding potential of -78 mV, manidipine did not suppress the Ca2+ current at
      concentrations less than 100 nM, but increased the Ca2+ current slightly at a
      concentration of 10 nM. The antagonistic effect of manidipine was significant at
      concentrations above 100 nM (IC50 = 400 nM). The voltage-dependent effect of
      manidipine on the Ca2+ current may explain the weak negative inotropism of
      manidipine in ventricular muscles, and provide an electrophysiological basis for
      its vascular selectivity.

PMID- 8287906
TI  - Muscarinic M2 receptors do not participate in the functional antagonism between
      methacholine and isoprenaline in guinea pig tracheal smooth muscle.
AB  - We investigated whether muscarinic M2 receptors, known to inhibit adenylyl
      cyclase activity in airway smooth muscle, also inhibit isoprenaline-induced
      relaxation of guinea pig tracheal smooth muscle, as has recently been described
      for the dog (Fernandes et al., 1992, J. Pharmacol. Exp. Ther. 262, 119). Smooth
      muscle strips were contracted with various concentrations of methacholine or
      histamine (which served as a control) in the absence or presence of the M2
      selective muscarinic receptor antagonist, gallamine (30 microM), and cumulative
      isoprenaline-relaxation curves were obtained. It was found that muscarinic M2
      receptor blockade had no significant effect on isoprenaline pD2 and Emax values,
      neither with histamine nor with methacholine. The results show that, in guinea
      pig trachea, muscarinic M2 receptors do not significantly influence the
      functional antagonism of cholinergic smooth muscle contraction by isoprenaline.

PMID- 8287907
TI  - Lack of effect of three putative vasoactive intestinal peptide receptor
      antagonists on vasoactive intestinal peptide-induced secretory responses in rat
      colon.
AB  - We have assessed the potential usefulness of three vasoactive intestinal peptide
      antagonists for investigating whether vasoactive intestinal peptide has a
      functional role as a secretomotor neurotransmitter at the neuroepithelial
      junction in rat colonic mucosa. Vasoactive intestinal peptide (VIP) increases
      short-circuit current in muscle-stripped preparations of rat colon. The response
      is unaffected by tetrodotoxin and can only be obtained when the peptide is
      applied to the basolateral side of the membrane. Three putative antagonists were
      tested for their ability to inhibit short-circuit current responses to vasoactive
      intestinal peptide. Vasoactive intestinal peptide-(10-28) (1 microM and 3
      microM), human growth hormone releasing factor (human GRF) analogue [Ac
      Tyr1]human GRF-(1-40)OH (0.1 microM and 1 microM) and
      [Lys1,Pro2,5,Arg3,4,Tyr6]VIP (0.5 microM) produced concentration-dependent
      increases in basal short-circuit current but were ineffective as antagonists to
      vasoactive intestinal peptide.

PMID- 8287908
TI  - Quinine and 4-aminopyridine inhibit the stimulatory output of dopamine in nucleus
      accumbens and the behavioural activity produced by morphine.
AB  - We have tested the effects in rats of two potassium channel blocking drugs, 4
      aminopyridine and quinine, on morphine-induced stimulation of behavioural
      activity and on dopamine outflow in nucleus accumbens using microdialysis.
      Morphine (1 mg/kg s.c.) increased dopamine output by 123% in nucleus accumbens.
      This dose of morphine also stimulated behavioural activity which in the early
      part of the time course corresponded closely with the increase of dopamine
      outflow in nucleus accumbens. Both of these effects were maximal 60-80 min after
      the morphine administration. 4-Aminopyridine (1 mg/kg i.p.) or quinine (50 mg/kg
      i.p.) injected 20 min before morphine inhibited the maximal effect on dopamine
      output by 88 and 80% respectively. Pretreatment with the two potassium channel
      blocking drugs also resulted in a reduction of morphine-induced stimulation of
      behavioural activity, 4-aminopyridine by 77% and quinine by 66%. In summary this
      study demonstrates that two drugs known to block potassium channels inhibit two
      effects of morphine associated with mesolimbic dopamine function.

PMID- 8287909
TI  - Intrathecal morphine-3-glucuronide does not antagonize spinal antinociception by
      morphine or morphine-6-glucuronide in rats.
AB  - Morphine or morphine-6-glucuronide either alone or in combination with morphine-3
      glucuronide was administered intrathecally to rats. Antinociceptive effects were
      evaluated with the tail flick and the hot plate tests. Motor function was tested
      using the rotarod test. Estimated ED50 from the dose-response curves for morphine
      and morphine-6-glucuronide showed about a 30 times more potent antinociceptive
      effect of morphine-6-glucuronide compared with morphine. Morphine-3-glucuronide
      had no antinociceptive effect. Simultaneous administration of morphine-3
      glucuronide 5.0 micrograms did not show any significant effect on antinociception
      induced by morphine 1.0 microgram or morphine-6-glucuronide 0.05 microgram.

PMID- 8287910
TI  - Endogenous nitric oxide counteracts antigen-induced bronchoconstriction.
AB  - In anesthetized, artificially ventilated guinea pigs immunized against ovalbumin,
      challenge with aerosolized ovalbumin (0.1 mg) elicited a substantial and
      sustained increase of insufflation pressure. The inhibitor of endogenous nitric
      oxide (NO) synthesis, L-NAME (N omega-nitro-L-arginine methylester, 30 mg kg-1
      i.v.), markedly augmented the response, the potentiation of which could be
      prevented by NO (20 p.p.m.) in the inhaled air. The results indicate an
      inhibitory effect of endogenous NO on antigen-induced bronchoconstriction.

PMID- 8287911
TI  - Pharmacological aspects of R-(+)-7-OH-DPAT, a putative dopamine D3 receptor
      ligand.
AB  - The R-(+)-isomer of 7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT) bound
      with a more than 200-fold higher affinity to cloned human dopamine D3 receptors
      (Ki = 0.57 nM) than to dopamine D2 receptors; the corresponding S-(-)-enantiomer
      had considerably less affinity for both dopamine receptor subtypes, indicating
      that the known enantiomer selectivity of 7-OH-DPAT for the 'classical' dopamine
      D2 receptor subtype extends to the recently discovered dopamine D3 receptor
      subtype. In rats R-(+)-7-OH-DPAT dose dependently (10-1000 nmol/kg) decreased
      dopamine release and induced yawning, while sniffing behaviour occurred at the
      highest dose tested (1000 nmol/kg). The possibility that the inhibition of
      dopamine release and the elicitation of yawning are mediated by dopamine D3
      receptors is considered.

PMID- 8287912
TI  - The effects of selective activation of the 5-HT3 receptor with m
      chlorophenylbiguanide on sleep and wakefulness in the rat.
AB  - The effects of the 5-HT3 receptor agonist, m-chlorophenylbiguanide, were compared
      with those of the 5-HT3 receptor antagonist, MDL 72222, in rats implanted with
      electrodes for chronic sleep recordings. m-Chlorophenylbiguanide (12.5-50.0
      micrograms) injected into the left lateral ventricle increased wakefulness and
      rapid eye movement (REM) sleep latency, whereas slow wave sleep, REM sleep and
      the number of REM periods were reduced. MDL 72222 (0.1-1.0 mg/kg, s.c.) induced a
      delayed and dose-dependent increase of slow wave sleep. Pretreatment with MDL
      72222 (0.1-0.5 mg/kg) prevented the effects of m-chlorophenylbiguanide (50
      micrograms) on wakefulness and sleep. It is suggested that the increase of
      wakefulness after 5-HT3 receptor activation could be related to the release of
      endogenous serotonin and dopamine.

PMID- 8287913
TI  - Effects of N6-cyclopentyl adenosine and 8-cyclopentyl-1,3-dipropylxanthine on N
      methyl-D-aspartate induced seizures in mice.
AB  - The effect of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and
      antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on N-methyl-D-aspartate
      (NMDA)-evoked seizures was studied in C57BL/6 mice (20/group). Animals were
      injected i.p. either with CPA (0.5, 1, 2 mg/kg) or CPX (1, 2 mg/kg) 15 min prior
      to administration of NMDA (30, 60, 125 mg/kg). Administration of NMDA alone
      resulted in a complete locomotor arrest at 30 mg/kg, while clonic/tonic seizures
      and progressively increasing mortality were seen at higher doses. Prior
      administration of CPA resulted either in a delay of seizure onset and unchanged
      mortality (0.5 mg/kg CPA, 60 mg/kg NMDA) or in elimination of tonic episodes and
      a significant reduction in postictal mortality (1, 2 mg/kg CPA; 60, 125 mg/kg
      NMDA). Pretreatment with CPX at either 1 or 2 mg/kg eliminated locomotor
      depression in animals injected with NMDA at 30 mg/kg. At 60 mg/kg NMDA, the
      effect of CPX administration resulted in mortality equivalent to that seen with
      125 mg/kg NMDA administered alone. The results indicate that A1 receptor agonists
      may protect against NMDA-evoked seizures and that the adenosine A1 receptor may
      be directly involved in these actions.

PMID- 8287914
TI  - Effects of chronic administration of adenosine A1 receptor agonist and antagonist
      on spatial learning and memory.
AB  - Spatial memory acquisition in Morris water maze was tested in C57BL/6 mice.
      Animals were injected once daily with different doses of either N6
      cyclopentyladenosine (CPA) or 8-cyclopentyl-1,3-dipropylxanthine (CPX). Drugs
      were administered for 9 days either concurrently with water maze testing (drugs
      injected 1 h after each trial), or prior to the entire block of trials. In the
      latter case, 1 day without injections preceded water maze experiments. Chronic
      administration of CPA resulted in a significant, dose-dependent reduction of
      target latencies, rapid development of spatial preference, and the absence of
      animals unable to perform the task. CPX treated animals did not show significant
      performance changes, and failed to develop spatial preference. Locomotor
      disturbances were not the cause of the observed effects. Our results indicate
      that chronic treatment with agents acting at adenosine A1 receptors results in
      behavioral effects that are significantly different from those observed following
      their acute administration. Therefore, particular caution is required in
      development of adenosine-based strategies targeted at neurodegenerative or
      cognitive disorders in which chronic treatment is advocated.

PMID- 8287915
TI  - Cocaine potentiates the blood pressure and cerebral blood flow response to
      norepinephrine in rats.
AB  - Acute drug-induced hypertension is known to have adverse consequences on the
      cerebral vasculature. Cocaine abuse has been reported to be associated with an
      increased frequency of hemorrhagic or ischemic stroke. The purpose of this study
      was to determine whether cocaine alters the blood pressure or cerebral blood flow
      response to exogenous norepinephrine. A craniectomy was made over the parietal
      cortex in rats and cortical blood flow changes were measured using laser-Doppler
      flowmetry. Ten minutes after cocaine (1 mg/kg, i.v.) or saline, increasing doses
      of norepinephrine (0.01-10 micrograms/kg, i.v.) were given by bolus injection and
      changes in blood pressure and flow were monitored. Cocaine produced a transient
      27 +/- 5% increase in blood pressure and a 38 +/- 9% increase in blood flow.
      Cocaine significantly potentiated the blood pressure and cerebral blood flow
      responses produced by submaximal pressor doses of norepinephrine (0.01-0.6
      microgram/kg, i.v.). In summary, cocaine causes a rapid, transient increase in
      blood pressure and cortical blood flow and potentiates the magnitude and duration
      of the pressure and flow response to norepinephrine. Repetitive blood pressure
      elevations in cocaine abusers is one of the proposed mechanisms leading to damage
      of cerebral vessels. These results may be relevant to an increased frequency of
      cerebrovascular accidents in cocaine-abusing individuals.

PMID- 8287916
TI  - Zaprinast increases cyclic GMP levels in plasma and in aortic tissue of rats.
AB  - The purpose of this study was to determine if significant relationships exist
      between plasma and aortic cyclic GMP (cGMP) levels and pharmacodynamic effect
      after the i.v. administration of the cGMP-selective phosphodiesterase inhibitor
      zaprinast to conscious, spontaneously hypertensive rats. Zaprinast dose
      dependently increased plasma and aortic cGMP levels at 10, 18 and 30 mg/kg and
      decreased mean arterial blood pressure (MAP) at 18 and 30 mg/kg. The
      concentrations of cGMP in the plasma and in the aorta were significantly
      correlated (r = 0.765, P < 0.0001). The changes in MAP were significantly
      correlated to aortic (r = -0.750, P < 0.0001) and plasma (r = -0.762, P < 0.0001)
      cGMP levels. We conclude that plasma cGMP may be an index of cGMP-selective
      phosphodiesterase inhibition in vivo.

PMID- 8287917
TI  - Characterization of endothelin receptors and localization of 125I-endothelin-1
      binding sites in human umbilical artery.
AB  - The mechanisms of endothelin-1-induced contractile response in the human
      umbilical artery were investigated in vitro. Autoradiography revealed 125I
      endothelin-1 binding sites in the smooth muscle layer of the vessel wall.
      Endothelin-1 and sarafotoxin S6b induced concentration-dependent contractions
      while endothelin-3 was virtually without contractile effect. The endothelin ETA
      receptor antagonist BQ 123 did not affect the contraction to endothelin-1 but
      antagonized the contraction to sarafotoxin S6b. The contraction to endothelin-1
      and sarafotoxin S6b was diminished by both verapamil and nicardipine. It can be
      concluded that endothelin-1 is a vasoconstrictor in the human umbilical artery,
      probably acting via more than one contraction-mediating receptor. The 125I
      endothelin-1 binding sites demonstrated in the smooth muscle layer of the vessel
      may correspond to receptors mediating the contractile effect. The mechanisms of
      action seems to involve activation of Ca2+ channels. The present study does not
      give any evidence for interaction of endothelin-1 with other endothelium-derived
      vasoactive agents in this vessel.

PMID- 8287918
TI  - Ca2+ channel antagonists enhance tension in skinned skeletal and heart muscle
      fibres.
AB  - Striated muscle fibres, both skeletal and cardiac of different species including
      human, skinned by freeze-drying, were activated in solutions strongly buffered
      for Ca2+. The single fibres were immersed in solutions with different [Ca2+].
      Sarcomere length was set and controlled by laser diffraction. Fibre type was
      determined by Sr2+ activation. The relation between the negative logarithm of the
      Ca2+ concentration and the normalized tension, the Ca2+ sensitivity curve, was
      investigated. The effect on the contractile machinery of three different Ca2+
      channel antagonists (verapamil, diltiazem and nifedipine) in a therapeutic
      concentration (10(-6) M) was investigated. The possible effects on the Ca2+
      sensitivity curve were quantified by: (1) the change in maximal tension developed
      at pCa2+ = 4.4; (2) the change in pCa2+ value at which 50% of the tension induced
      at pCa2+ = 4.4; (3) the steepness of the Ca2+ sensitivity curve in this point.
      The three drugs tested, at a therapeutic concentration of 1 microM, all enhanced
      maximal induced tension by respectively 25, 20 and 7%. The sarcomere length
      dependency of the effect proved to be dependent upon the drug, but also slightly
      on fibre type (skeletal or cardiac), or on species. It is concluded that the drug
      influences the cooperativity of the two different types of binding sites on
      troponin-C (low- and high-affinity sites). Tension enhancement was due to
      increased stiffness of the actin-myosin interaction site.

PMID- 8287919
TI  - The hypoglycemic sulphonylurea tolbutamide increases N-methyl-D-aspartate- but
      not kainate-activated currents in hippocampal neurons in culture.
AB  - The effects of the hypoglycemic sulphonylurea tolbutamide, a marker of K(+)-ATP
      channels, on the N-methyl-D-aspartate- (NMDA) and kainate-activated currents were
      studied in rat hippocampal neurons in culture, using the patch-clamp technique in
      a whole-cell configuration. Tolbutamide (500 microM) reversibly increased the
      peak amplitude and the steady state level of NMDA- but not kainate-evoked
      currents. This effect was not glycine dependent as it was observed at low and
      saturated concentrations of glycine. The affinity of the NMDA receptor-channel
      complex for glycine did not change in the presence of tolbutamide. The action of
      tolbutamide on the NMDA-activated current was not mediated by K(+)-ATP channels
      since CsCl was added intracellularly at concentrations which completely blocked
      all K+ channels. Possible mechanisms explaining the effect of tolbutamide via the
      modulation of intracellular messengers are discussed.

PMID- 8287920
TI  - The process of reinnervation in the dentate gyrus of adult rats: temporal
      relationship between changes in the levels of glial fibrillary acidic protein
      (GFAP) and GFAP mRNA in reactive astrocytes.
AB  - The present study evaluates the temporal relationships between increases in glial
      fibrillary acidic protein (GFAP) mRNA, GFA protein levels, and GFAP
      immunostaining in the hippocampus of adult rats following unilateral lesions of
      the entorhinal cortex (EC). GFAP mRNA levels were assessed at 12 h, 1, 2, 4, 6,
      8, 10, 12, 14, and 30 days postlesion by dot blot assays using 35S-labeled cRNA
      probes against the mRNA. Animals were also prepared for in situ hybridization
      during the peak of GFAP mRNA expression (2 days postlesion) to explore the nature
      of individual differences in the spatial extent of the increases. GFA protein
      levels were assessed by Western blot and dot immunoblot techniques in a separate
      group of animals prepared at 1, 2, 4, 6, 8, and 10 days postlesion and by
      immunostaining at 1, 2, 4, 6, and 8 days postlesion. The dot blot analyses of
      GFAP mRNA levels confirmed previous studies, in that we observed dramatic
      increases in the levels of GFAP mRNA in the hippocampus ipsilateral to the EC
      lesions. The increases were biphasic, with a large peak in mRNA levels at 1-2
      days postlesion (about 10-fold greater than control) and a second peak at 6-8
      days. In most animals, the increases were predominantly ipsilateral to the
      lesion. However, in some animals, there were also large increases on the
      contralateral side. In situ hybridization experiments revealed two different
      spatial patterns of increased gene expression, one in which the increases in GFAP
      mRNA occurred bilaterally and one in which increases were restricted primarily to
      the hippocampus ipsilateral to the lesion. Immunochemical measures revealed that
      GFA protein levels increased gradually in the hippocampus ipsilateral to the
      lesion, reaching a peak at about 2-fold higher than control at 4 days postlesion,
      and then remained near this level until at least 10 days postlesion. In the
      contralateral hippocampus, GFA protein levels were increased to about the same
      extent as on the ipsilateral side at 1, 2, and 4 days postlesion, but then began
      to decline, returning to near control levels by 8 days. Increases in
      immunostaining occurred with about the same time course as the increases in GFA
      protein levels as measured immunochemically. These results define the temporal
      relationship between increases in GFAP mRNA and increases in GFA protein,
      providing new insights into the regulation of gene expression in reactive
      astrocytes.

PMID- 8287921
TI  - gamma-Acetylenic GABA produces axon-sparing neurodegeneration after focal
      injection into the rat hippocampus.
AB  - In exploring the recently discovered phenomenon of indirect excitotoxicity, we
      noted that intrahippocampal injections of the nonspecific aminotransferase
      inhibitor gamma-acetylenic GABA (GAG; 60-240 nmol) caused excitotoxic lesions in
      rats. When assessed 3 days following the injection, GAG was shown to be
      approximately equally toxic to CA3/hilar neurons and CA1 pyramids, while CA2
      neurons and granule cells were clearly less vulnerable. Choline acetyltransferase
      activity, a marker of extrinsic afferents, remained unchanged in the GAG-lesioned
      hippocampus, indicating the axon-sparing nature of the insult. In contrast, a
      lesion caused by 240 nmol of GAG resulted in a significant reduction in 3H-MK-801
      binding, which was used as a marker for NMDA receptor-bearing hippocampal
      neurons. GAG-induced lesions were blocked by the NMDA receptor antagonists MK-801
      and AP7 but were not influenced by the nature of the anesthetic used during
      surgery. Iontophoretic application of GAG did not excite CA1/CA3 cells in the rat
      hippocampus. In vitro, GAG proved to be a relatively potent inhibitor (IC50: 43
      microM) of kynurenine aminotransferase, the biosynthetic enzyme of the endogenous
      neuroprotectant kynurenic acid. GAG also inhibited the neosynthesis of kynurenic
      acid in hippocampal slices (IC50: 790 microM). Thus, GAG shares several
      characteristics of the recently described indirect excitotoxin aminooxyacetic
      acid (AOAA; Exp. Neurol. 113: 378, 1991). GAG and AOAA appear to belong to a new
      family of excitotoxic agents which produce lesions indirectly by metabolic
      derangement and/or inhibition of kynurenate production.

PMID- 8287922
TI  - Osmotic effects upon the theta rhythm, a natural brain oscillation in the
      hippocampal slice.
AB  - Raising plasma osmolality reduces patient susceptibility to generalized tonic
      clonic seizure. In brain slices, elevated osmolality reduces epileptiform
      discharge. Conversely, lowering osmolality can induce generalized tonic-clonic
      seizure in patients and promotes epileptiform activity in hippocampal or
      neocortical slices. Rhythmic slow activity or "theta" encodes memory in some
      mammals and represents a nonpathological oscillation of cortical neurons. In
      hippocampal slices, theta consists of a 4-10 Hz oscillation overriding a slow
      depolarization (SD) that recurs periodically. We examined if the theta rhythm,
      which is a natural brain oscillation, was affected by clinically relevant changes
      in osmolality. Theta was induced by bath application of 40 microM carbachol and
      intracellularly recorded in individual CA3 neurons of the rat hippocampal slice.
      Artificial CSF (ACSF) elevated by 40 milliosmoles (+40 mOsm) using mannitol
      slowed the SD frequency in 18 of 18 CA3 neurons. Conversely -40 mOsm ACSF
      increased SD frequency in 12 of 14 neurons. Osmotic alteration did not change
      theta frequency in 9 of 9 CA3 cells, but overriding action potentials were
      reduced in number or eliminated by hyperosmotic ACSF in 8 of 12 neurons.
      Elevation of osmolality with glycerol, which does not alter cell volume, had no
      effect in 4 of 4 neurons. This indicated that the induced changes in excitability
      resulted from alterations in cell volume. We examined if osmotically induced
      changes in cell volume might alter the glial capacity to buffer K+ released by
      neuronal discharge. Intracellular recordings from glial cells revealed that
      osmolality had no significant effect upon the glial resting potential
      itself.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287923
TI  - Rapid synaptic changes and bundling in the supraoptic dendritic zone of the
      perfused rat brain.
AB  - In the dendritic region of the supraoptic nucleus of young adult rats we found
      ultrastructural evidence of rapid (< 30 min) morphological reorganization
      following transcardial perfusion of the anesthetized animals with high (325
      mOsm), but not with normal, osmolality (302 mOsm) balanced salt solutions. The
      changes observed included significant increases in dendritic bundling and
      increased numbers of multiple axodendritic synapses (where one presynaptic
      terminal contacted two or more postsynaptic dendrites). In our initial
      experiments the perfusion medium contained tannic acid, but when the tannic acid
      was omitted in a separate set of experiments, the results were both similar and
      more striking. These studies indicate that the plasticity previously seen in this
      region under physiological conditions can occur rapidly and probably involves
      astrocytic process withdrawal from between adjacent dendrites. This change in the
      distribution of astrocytic processes allows previously single synapses access to
      additional postsynaptic dendritic membrane. Together, increased dendritic
      bundling and multiple synapses may facilitate the synchronization of cell firing
      and, thus, hormone release.

PMID- 8287924
TI  - Developmental expression of neuron-specific enolase immunoreactivity and
      cytochrome oxidase activity in neocortical transplants.
AB  - The present study has examined certain metabolic markers in fetal neocortical
      tissue transplanted to the cortex, hippocampus, striatum, or ventricle.
      Particularly, the immunocytochemical expression of neuron-specific enolase (NSE)
      was studied in a series of host rats ranging between 10 days and 15 months
      postoperative. NSE is a major glycolytic pathway enzyme found in all neurons. The
      antibody to NSE is a very reliable marker for neuronal functional metabolic
      activity and developmental status and its onset has been shown to coincide with
      synaptic connections. In some grafts oxidative metabolic status was investigated
      using cytochrome oxidase (CO) histochemistry. In addition, the normal development
      of NSE expression in rat neocortex was also examined. In normal development, NSE
      was weakly expressed in fetal brain, but by 1-2 weeks postnatal the enzyme was
      strongly expressed in all neurons. Typical cortical laminar patterns were evident
      at 30 days with neurons in layer V and scattered interneurons the most strongly
      stained. In cortex-cortex transplants NSE expression was very weak; at 1-3 weeks
      postoperative, it was practically nonexistent; and at all later times only a
      minority of neurons had normal expression when compared to that in normal
      development even though by Nissl staining standards in adjacent sections they
      appeared "normal." Labeling indices ranged between 30 and 49%. Intraventricular
      grafts had consistently low NSE expression with labeling indices ranging between
      18 and 46%. However, when the neocortical tissue was placed in other regions,
      neuronal NSE appeared only slightly below normal. CO histochemistry corroborated
      the NSE activity with regards to graft placement. Several possibilities that may
      account for reduced NSE profile in transplanted neurons include incomplete
      migration patterns, reduced synaptic connectivity, and potential ischemia causing
      lowered protein synthesis during reestablishment of vascular connections. If
      neuronal glycolysis is weakened, it is possible that neurotransmitter production
      or axonal transport are reduced. Since most energy capacity in brain is dependent
      on the glycolytic sequence for oxidative metabolism, reduced glycolytic capacity,
      as depicted by NSE expression, may suggest the presence of transplanted neurons
      that have adapted to their new environment with a relatively immature profile.

PMID- 8287925
TI  - Postnatal rat NADPH-diaphorase-containing myenteric neurons extend processes when
      transplanted into adult rat corpus striatum.
AB  - Pieces of isolated myenteric plexus, freshly dissected from the colon of young
      inbred Fischer rats, were implanted unilaterally into the corpus striatum of
      adult Fischer rats which had received a prior quinolinic acid lesion. Similar
      implants were made into the unlesioned striatum of a second group of Fischer
      rats. The survival of a subpopulation of grafted neurons, and the incidence of
      fiber outgrowth from these neurons into the host striatum, was examined after 3
      and 6 weeks using a histochemical technique for the demonstration of nicotinamide
      adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) activity. This
      enzyme is found both in some enteric neurons and a subpopulation of striatal
      neurons. Grafted enteric neurons expressing NADPH-diaphorase were easily
      distinguished in both the lesioned and unlesioned host striata at 3 and 6 weeks
      postimplantation. Fibers could be found extending from NADPH-diaphorase
      containing enteric neurons into both the lesioned and unlesioned corpus striatum,
      although fewer graft-derived fibers were seen in the unlesioned striatum. This is
      the first demonstration that enteric neurons transplanted into the adult
      mammalian brain are capable of extending processes into the surrounding CNS
      tissue.

PMID- 8287926
TI  - Intrastriatal injections of quinolinic acid or kainic acid: differential patterns
      of cell survival and the effects of data analysis on outcome.
AB  - There is controversy about the extent to which lesions of the rat striatum with
      excitatory amino acids mimic the cellular pathology seen in Huntington's Disease
      (HD). We sought to resolve this debate by determining with cell counts in
      adjacent sections the patterns of survival of medium spiny and aspiny striatal
      neurons using enkephalin immunohistochemistry and NADPH-diaphorase histochemistry
      as markers of these cell populations, respectively. Results showed that 2 weeks
      after quinolinic acid lesions, cell loss was qualitatively similar for the two
      cell groups. However, by varying the size of the sampling area for quantitative
      analyses and its distance from the lesion zone, the outcome of the statistical
      analyses varied enormously. Thus, a relative sparing of NADPH-diaphorase-labeled
      cells compared to enkephalin-labeled cells could be detected quantitatively in
      transition areas bordering the lesion under some but not all analytical
      conditions. Kainic acid lesions depleted both cell populations similarly, except
      in regions of transition farthest from the lesion, where enkephalin-containing
      neurons were more resistant than NADPH-diaphorase-containing cells. The size of
      the transition area around the lesion also differed depending upon excitotoxin
      and cell population. These results help to reconcile the controversy and suggest
      that with highly specified quantitative conditions quinolinic acid-induced injury
      of the striatum can resemble the histopathology of HD.

PMID- 8287927
TI  - Synaptic and dendritic pathology in murine retroviral encephalitis.
AB  - Central nervous system (CNS) damage occurs during retroviral infection in both
      man and animals. As a model of human disease, we studied the distribution and
      extent of CNS damage during retroviral infection with two molecularly cloned,
      neurotropic murine leukemia viruses. Both viruses mediate a spongiform
      encephalopathy involving predominantly the brainstem and spinal cord. During the
      course of disease, immune reactivity for synaptophysin (SYN) (to identify
      presynaptic elements) and microtubule-associated protein-2 (MAP-2) (to identify
      postsynaptic elements) were quantified using confocal laser microscopy.
      Immunostaining of SYN in the cerebral cortex (an area not exhibiting spongiform
      lesions) was similar in viral infected and age-matched control mice. However,
      compared to age matched controls, SYN staining in the brainstem (an area
      exhibiting spongiform lesions) of viral infected mice progressively declined
      during the course of disease. Quantitative analysis showed greater reduction of
      MAP-2 immunostaining in viral-infected mice compared to age-matched controls. In
      infected mice, both regions with and without spongiform lesions showed diminished
      MAP-2 staining. Widely distributed microscopic vacuolation of dendritic processes
      was observed in confocal preparations. These findings suggest primary dendritic
      damage in murine retroviral infection of the CNS similar to what has been
      described in human immunodeficiency virus-1 encephalitis.

PMID- 8287928
TI  - beta-Amyloid of Alzheimer's disease induces reactive gliosis that inhibits axonal
      outgrowth.
AB  - Pathological lesions in the brains of patients with Alzheimer's disease (AD) are
      characterized by dense deposits of the protein beta-amyloid. The link between the
      deposition of beta-amyloid in senile plaques and AD-associated pathology is, at
      present, controversial since there have been conflicting reports on whether the
      39-43 amino acid beta-amyloid sequence is toxic or trophic to neurons. In this
      report, we show that beta-amyloid peptide when presented as an insoluble
      substrate which mimics its conformation in vivo can induce cortical glial cells
      in vitro and in vivo to locally deposit chondroitin sulfate containing
      proteoglycan. In vitro the proteoglycan-containing matrix deposited by glia on
      beta-amyloid blocks the usual ability of the peptide to allow cortical neurons to
      adhere and grow. Chondroitin sulfate-containing proteoglycan was also found in
      senile plaques of human AD tissue. We suggest that an additional effect of beta
      amyloid in the brain, which compounds the direct effects of beta-amyloid on
      neurons, is mediated by the stimulation of astroglia to become reactive. Once in
      the reactive state, glial cells deposit large amounts of growth-inhibitory
      molecules within the neuropil which could impair neuronal process survival and
      regeneration leading to neurite retraction and/or dystrophy around senile plaques
      in AD.

PMID- 8287929
TI  - The dynamics of cell death in the olfactory epithelium.
AB  - Adult vertebrate olfactory epithelia are unique in their continual sensory neuron
      turnover and replacement. This paper describes studies of various aspects of the
      death of these receptor neurons in unoperated rats and at 12 days and 7 weeks
      after unilateral ablation of the olfactory bulb, the receptor neuron synaptic
      target. Particular attention has been focused on the lifespan of the dying cells
      using tritiated thymidine/autoradiography to examine their "birthdates." We show
      that in control epithelia 25-30% of the degenerating (pyknotic) cells were
      located in the basal quarter of the epithelium, the location of the least mature
      sensory neurons and of neuronal stem cell proliferation. Birthdate analysis shows
      that 2-5% of the degenerating cells were dying within a day or less of their
      "birth." Thus, a sizeable proportion of these cells were dying precociously,
      before achieving full neuronal maturation. A further 65% of the dying cells
      occurred in the middle half and 7% in the apical quarter of the epithelium.
      Following unilateral olfactory bulbectomy, a two- to threefold increase in the
      number of degenerating cells occurred in ipsilateral versus contralateral tissue.
      This was maintained through the 7-week experimental period. A shift of 10-15% of
      the total degenerating cell numbers from the basal to middle region of the
      epithelium also occurred. Despite the increased degenerative activity
      ipsilaterally, the proportion of dying cells labeled autoradiographically
      remained the same on both sides at most labeling periods. However, a striking
      wave of enhanced cell death of 6- to 7-day-old neurons over the contralateral
      levels occurred ipsilaterally in both the 12-day and 7-week postbulbectomy
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287930
TI  - Neuritic involvement within bFGF immunopositive plaques of Alzheimer's disease.
AB  - As early as 1928, Cajal suggested that plaques contain a trophic substance which
      attracts neurites. Recently, basic fibroblast growth factor (bFGF) levels were
      shown to be elevated in Alzheimer's disease (AD) and localized to plaques and
      neurofibrillary tangles. We sought to clarify the subtype of plaques which
      contain bFGF and provide more detail on bFGFs neuronal and vascular localization
      in normal aged brain, AD brain, and Down's syndrome (DS) brain. We combined
      double-labeling immunocytochemistry for bFGF with heparan sulfate
      glycosaminoglycans, beta-amyloid, and thioflavine fluorescence. In addition, the
      neuritic markers tau-1 and PHF-1 were combined with bFGF staining. Eleven AD,
      five nondemented controls, and four DS cases were examined. Most bFGF
      immunopositive plaques contained numerous dystrophic fibers, indicating they were
      of the neuritic subtype. We also detected a variety of bFGF-positive cells,
      including hilar, dentate granule, pyramidal, and stellate neurons, as well as
      astrocytes. The basement membrane of large and small arterioles also contained
      bFGF. bFGF immunoreactivity within neurons, astrocytes and the vasculature was
      increased in AD cases relative to controls. Immunoreactivity within the DS cases
      was intermediate. These results suggest that bFGF is up-regulated in AD and
      support the hypothesis that bFGF may attract neurites into plaques.
      Alternatively, an injured neurite may induce bFGF production by responding glia,
      resulting in further neuritic attraction.

PMID- 8287932
TI  - Regional and cell-specific expression of GDNF in rat brain.
AB  - The survival of ventral mesencephalic substantia nigra (SN) dopamine neurons,
      which degenerate in Parkinson's disease, is enhanced by glial cells in vitro. The
      recent isolation of glial cell line-derived growth factor (GDNF), a molecule with
      apparently selective effects on dopamine (DA) neurons in vitro, raises the
      question of whether this factor is found in normal brain cells. In this study,
      the polymerase chain reaction (PCR) was employed to determine the regional
      distribution and cellular localization of GDNF in the rat central nervous system.
      GDNF was expressed by SN and basal forebrain Type 1 (T1) astrocytes, with trace
      transcript levels present in cortical T1 astrocytes. Neuronal cultures of
      embryonic SN also expressed GDNF. Regionally, postnatal striatum contained the
      highest GDNF mRNA levels in vivo under the PCR conditions employed. Our data
      suggest a role for GDNF in both local and target-derived support of DA neurons,
      as well as potential involvement in the support of other neuronal populations in
      vivo.

PMID- 8287931
TI  - Consequences of reduced cerebral blood flow in brain development. II. Retardation
      of neurological outcome and phosphorus metabolism.
AB  - We investigated the temporal relationship of the emergence of biochemical
      abnormalities to the development of behavioral dysfunction to identify the
      central factors of ischemic neurological disorders in developing brains. To
      induce early ischemia, bilateral carotid artery occlusion (BCAO) was surgically
      performed on 21 cats at the second week of age. BCAO produces histopathological
      damage, including neuronal loss and thinning of white matter. 31P magnetic
      resonance spectroscopy was used to monitor brain oxidative metabolism, neuronal
      membrane growth, and myelination of the prefrontal cortex in the first 3 months.
      Neurological development was monitored by conducting 25 tests of reflex, motor,
      sensory, and integrated behavioral function. At 1 month, phosphodiester (PDE)
      levels, a component of membranes and myelin, were low in animals showing complete
      ligation. At 2 months, the growth of PDE was low (1/4 to 1/2 of normal) in BCAO
      animals, whereas normal animals demonstrated a 23% increase. Phosphocreatine
      (PCr) levels, indicated by PCr/ATP and PCr/inorganic phosphate ratios, were
      retarded at 2 months in completely ligated animals (1/4 of normal).
      Neurologically, the completely ligated animals showed retardation of general
      development. The retardation was most pronounced for integrative functions,
      including visual function, and became more pronounced later in development. The
      time course of emergence of the retardation generally coincided with emergence of
      abnormalities in phosphorous compounds. The simultaneous occurrence of several
      biochemical and functional abnormalities in development following early ischemic
      insult suggests a causal relationship between membrane and mitochondrial
      development and neurological function.

PMID- 8287933
TI  - Reinnervation of adult rat gastrocnemius muscle by embryonic motoneurons
      transplanted into the axotomized tibial nerve.
AB  - In some cases of spinal cord injury and in certain motoneuron diseases, such as
      amyotrophic lateral sclerosis and spinal muscular atrophies, lower motoneurons
      are destroyed and muscle function cannot be restored except by reinnervation from
      alternate motoneuron sources. We have tested the feasibility of employing local
      transplantation of embryonic motoneurons to restore innervation to denervated
      somatic muscle as a first step in salvaging muscle function and enabling use of
      functional electric stimulation. Dissociated ventral spinal cord cells from
      Embryonic Days 14 and 15 rats were transplanted into the distal stump of
      axotomized tibial nerves of adult rats. Animals were killed 3-18 weeks after
      transplantation. After 3 weeks large multipolar cells, resembling alpha
      motoneurons, were observed within the transplant site surrounded by myelinated
      and unmyelinated axons and dendrites. Axons emanating from these transplanted
      motoneurons were identified within the nerve stump and within the previously
      denervated gastrocnemius muscle, forming neuromuscular junctions. Transplanted
      motoneurons survived up to 18 weeks and were labeled after intramuscular
      injection of fast blue. This study demonstrates that embryonic spinal
      motoneurons, transplanted into the distal adult peripheral nerve stump, are able
      to survive and reinnervate the denervated target muscle. We are now exploring the
      possibility of using this experimental approach to retard the atrophy of
      denervated skeletal muscle, thus providing a muscle capable of useful response to
      functional electrical stimulation.

PMID- 8287934
TI  - NGF increases brain astrocyte number in culture.
AB  - Nerve growth factor (NGF) promotes survival and maintenance of peripheral and
      central neurons. In previous studies, we found that low-affinity NGF binding
      sites were associated with flat nonneuronal cells dissociated and cultured from
      the embryonic septum. These cells were also labeled with a monoclonal antibody to
      the NGF receptor, 192 IgG, suggesting that low-affinity NGF receptors are
      associated with a nonneuronal population. To define the potential effect of NGF
      on these nonneuronal cells, rat Embryonic Day 17 (E17) septa were dissociated and
      cultured in fully defined medium in the presence of NGF. Glial fibrillary acidic
      protein (GFAP) was used as a marker for the astrocyte population. NGF elicited a
      dramatic ninefold increase in the number of GFAP-positive cells after 7 days. NGF
      similarly increased astrocyte number in cultures grown from E18 hippocampi and
      E16 substantia nigra, suggesting that NGF acts on glia from multiple brain
      regions. To begin defining the mechanism of NGF action on astrocytes, we examined
      [3H]thymidine incorporation, which increased significantly, but by only 50%, upon
      exposure to the trophic factor. We tentatively conclude that NGF increases
      astrocyte number in culture by stimulating mitosis as well as enhancing survival
      or differentiation.

PMID- 8287935
TI  - Medial frontal cortex lesions: deficits and treatment with nimodipine.
AB  - Rats with bilateral lesions of the medial frontal cortex were tested in a T-maze
      for the ability to learn a position habit and to make four reversals of it. Rats
      with medial frontal cortical lesions showed deficits in reversal learning. In
      addition, they were found to be hyperactive in an open field. Treatment with the
      dihydropyridine calcium channel antagonist, nimodipine, did not reduce these
      behavioral deficits.

PMID- 8287936
TI  - Immortalized GABAergic cell lines derived from rat striatum using a temperature
      sensitive allele of the SV40 large T antigen.
AB  - Embryonic striatal cells were immortalized using the A58 temperature-sensitive
      allele of the SV40 large T antigen. Two cell lines, M213-2O and M26-1F, with
      gamma-aminobutyric acid (GABA)ergic properties were selected from 85 clones thus
      developed. M213-2O is a multipolar, polygonal cell line which expresses SV40
      large T antigen and glutamate decarboxylase (GAD) at the permissive temperature
      (33 degrees C) and GAD and MAP-2 immunoreactivity at the nonpermissive
      temperature (39.3 degrees C). M26-1F has a fibroblast-like morphology and
      expresses SV40 large T antigen and GAD both at the permissive and nonpermissive
      temperatures and MAP-2 immunoreactivity at the nonpermissive temperature. Both
      lines contain GABA as measured by reversed-phase HPLC and M213-2O expresses
      nipecotic-sensitive [14C]GABA uptake.

PMID- 8287937
TI  - Adhesion molecule antagonists: future therapies for allergic diseases?

PMID- 8287938
TI  - No added benefit from nebulized amiloride in patients with cystic fibrosis.
AB  - In cystic fibrosis (CF) airway epithelial sodium absorption is increased 2-3
      fold. Since sodium absorption is inhibited by the sodium channel blocker
      amiloride, our aim was to assess its therapeutic benefit in cystic fibrosis. A
      randomized, double-blind, placebo-controlled, cross-over trial of nebulized
      amiloride was performed in 23 patients with cystic fibrosis. Amiloride or placebo
      was administered four times daily for two six month periods. Existing treatment
      was continued, and any infective exacerbations treated in the usual way. Fourteen
      patients completed the study. No significant changes occurred in forced
      expiratory volume in one second, forced vital capacity, oxygen saturation, body
      weight, sputum volume, culture and rheology, serum urea, and electrolytes, white
      cell count and erythrocyte sedimentation rate during either treatment period. The
      frequency of infective exacerbations was also not different in either treatment
      period. We were thus unable to confirm the benefit shown in the only other
      clinical trial of nebulized amiloride in cystic fibrosis and conclude that, in
      the presence of established treatment for cystic fibrosis lung disease, nebulized
      amiloride offers no additional clinical benefit.

PMID- 8287939
TI  - Airway inflammation in symptomatic and asymptomatic children with methacholine
      hyperresponsiveness.
AB  - A definition of asthma includes symptoms due to reversible airflow limitation and
      airway hyperresponsiveness. Characteristically, there is also airway
      inflammation. In children with methacholine airway hyperresponsiveness but no
      asthma symptoms, we examined whether there were features of asthmatic airway
      inflammation. Forty one children, aged 11-16 yrs, were studied. Thirteen
      asymptomatic children with methacholine airway hyperresponsiveness (provocative
      concentration producing a 20% fall in forced expiratory volume in one second
      (PC20) geometric mean of 3.35 (range 1.08-7.81) mg.ml-1) were compared with 13
      currently symptomatic asthmatics with a similar PC20 of 1.91 (0.42-6.5) mg.ml-1
      and 13 normal children with a normal PC20 of 52.4 (17.6 to > 64) mg.ml-1.
      Breathlessness experienced during a methacholine test was recognized to have
      occurred previously in 7 out of 13 asymptomatic children and all symptomatic
      children. Asymptomatic children had significantly more airway responses to
      hyperventilation with cold dry air (4 out of 13) than normal children (0 out of
      13) but less than symptomatic children (11 out of 15). Sputum induced with
      hypertonic saline contained lower eosinophil counts in the asymptomatic children
      (median (interquartile range) 0.20 (0.59)%) than in the symptomatic children
      (1.70 (9.45)%), and not different from the normal children (0.15 (0.61)%).
      Budesonide, 400 micrograms b.i.d. improved respiratory symptoms, forced
      expiratory volume in one second (FEV1) and methacholine PC20 in symptomatic
      children, but this effect did not reach statistical significance in asymptomatic
      children. We conclude that symptomatic children are more likely to have evidence
      of asthmatic inflammation than asymptomatic children and this probably explains
      the symptom difference.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287940
TI  - The distribution of adhesive mechanisms in the normal bronchial epithelium.
AB  - The integrity of the bronchial epithelium is dependent on various adhesion
      mechanisms that serve to hold the composite structure of the epithelium together
      and anchor it to the underlying basement membrane. Using immunohistochemistry we
      wanted to map out a number of these junctional and non-junctional adhesion
      mechanisms in the normal human bronchial epithelium. The beta 1-associated
      integrin subunit alpha 2 was immunolocalized to all of the epithelial
      intercellular spaces, whilst alpha 6 and beta 4 were strongly evident at the
      basal cell layer basement membrane junction. The alpha 1 and alpha 5 integrin
      subunits were not detected anywhere in the epithelium. Monoclonal antibodies
      (MoAbs) to tight junction polypeptides and the E-cadherin, liver cell adhesion
      molecule (LCAM), immunolocalized to the apicolateral portions of the
      intercellular junctions between all neighbouring columnar cells, with LCAM
      extending further along the lateral cell membrane. Desmosomal protein (dp) 1 and
      2 MoAbs gave a punctate pattern between all of the suprabasal cells, and
      exhibited the greatest intensity of staining at the junction between the columnar
      and basal cell layers. In conclusion, there is an organized distribution of
      adhesive mechanisms within the normal human bronchial epithelium, which may be
      targeted by the various insults which lead to epithelial shedding.

PMID- 8287941
TI  - Long-term oxygen therapy in parenchymal lung diseases: an analysis of survival.
      The Swedish Society of Chest Medicine.
AB  - We have analysed the predictors of survival in patients starting long-term
      domiciliary oxygen therapy (LTO) for chronic hypoxia caused by parenchymal lung
      disease. In 240 patients (136 males) LTO was started at a mean age of 70 yrs.
      Survivors have been followed up for a minimum of 28 months (range 28-57 months).
      Interstitial fibrosis was the sole cause of hypoxia in 51 patients, and late
      sequelae of pulmonary tuberculosis in 48 patients. More than one (mixed) disease
      caused hypoxia in 124 patients. Patients with tuberculosis (TB) started LTO with
      significantly higher values of arterial carbon dioxide tension (PaCO2) and
      markedly lower spirometry volumes than patients with interstitial fibrosis. In
      the total patient group survival was correlated in the univariate analysis to
      cause(s) of hypoxia, performance status and PaCO2 when breathing air. TB had a
      relatively good prognosis, whilst interstitial fibrosis implied a poor long-term
      survival. A PaCO2 of below 5.5 kPa and a poor performance class was associated
      with increased mortality rates. In TB patients, survival was better when thoracic
      deformity contributed to hypoxia. In patients with interstitial fibrosis, a
      forced vital capacity of below 2.1 l was associated with increased mortality.
      Concomitant chronic obstructive pulmonary disease was associated with better
      survival than interstitial fibrosis alone. In the multivariate analysis, survival
      was found correlated to performance status, presence or absence of thoracic
      deformity and forced expiratory volume in one second (FEV1) and forced vital
      capacity (FVC).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8287942
TI  - Quantitative importance of asbestos as a cause of lung cancer in a Swedish
      industrial city: a case-referent study.
AB  - We wanted to assess the quantitative importance of asbestos as a cause of lung
      cancer. In a case-referent study, the exposure to asbestos, tobacco smoke and
      some other occupational exposures were compared between 147 cases of lung cancer
      (100 men, 47 women), 111 hospital referents, and 109 population referents, all
      below the age of 75 yrs and living in an industrial city. The attributable risk
      of lung cancer due to asbestos exposure was 16% in men (95% confidence interval 1
      31%). No woman had occupational exposure to asbestos. We conclude that in the mid
      1980's tobacco smoking was the major attributable risk, being 95% for men and 78%
      for women, but that in men asbestos was an appreciable contributing factor in the
      general population of a Swedish industrial city.

PMID- 8287943
TI  - Bronchoalveolar lavage in extrinsic allergic alveolitis: effect of time elapsed
      since antigen exposure.
AB  - The aim of the present study was to investigate whether bronchoalveolar lavage
      (BAL) cell profile and immunoglobulin levels from patients with extrinsic
      allergic alveolitis (EAA) were related to the time elapsed between last antigen
      exposure and BAL. For this purpose, an analysis was performed of BAL fluid (BALF)
      obtained from 59 nonsmoking EAA patients at various time-points after termination
      of antigen exposure and BAL. BALF early after antigen provocation (group 1: < 24
      h) contained high absolute and relative numbers of lymphocytes, neutrophils,
      eosinophils and mast cells, and a low relative number of alveolar macrophages.
      When obtained after recent antigen exposure (group 2: 2-7 days), BALF showed high
      numbers of lymphocytes, plasma cells and mast cells, and high levels of
      immunoglobulins M, G and A (IgM, IgG and IgA). In BAL obtained one week or more
      after the final antigen exposure, (Group 3: 8-30 days; Group 4: 1-12 months) the
      distribution of all constituents showed a tendency to return to normal values,
      with the exception of the lymphocytes. These results demonstrate that BAL cell
      profile and immunoglobulin levels in EAA are highly dependent on the time-point
      at which the material is obtained in relation to the last exposure to the
      causative antigen.

PMID- 8287944
TI  - Plasma lactate dehydrogenase: a marker of disease activity in cryptogenic
      fibrosing alveolitis and extrinsic allergic alveolitis?
AB  - Total plasma lactate dehydrogenase (LDH) activity may be elevated in cryptogenic
      fibrosing alveolitis (CFA) and extrinsic allergic alveolitis (EAA), and may be a
      useful monitor of disease progress. In a retrospective, primary referral centre
      study, we compared LDH at presentation, prior to bronchoalveolar lavage BAL, and
      after treatment and follow-up with changes in pulmonary function, in patients
      with CFA, EAA and pulmonary sarcoidosis. Plasma levels of LDH at presentation in
      CFA (n = 47) and EAA (n = 10) were significantly higher than in patients with
      sarcoidosis (n = 36). LDH activity decreased in patients with improving lung
      function (EAA, p = 0.008; CFA, p = 0.02), whereas it increased in CFA patients
      with deteriorating lung function (p = 0.015). Total plasma LDH is a simple,
      though nonspecific test, which appears to reflect changes of disease activity in
      patients with CFA and EAA.

PMID- 8287945
TI  - Abnormal alveolar macrophage populations in bone marrow transplant recipients
      with pneumonitis.
AB  - The purpose of this investigation was to determine whether there is any
      relationship between different subsets of alveolar macrophages and type of
      infection or survival from interstitial pneumonitis following bone marrow
      transplantation (BMT). The population of alveolar macrophages found in
      bronchoalveolar lavage fluid (BALF) from 16 BMT recipients with 19 episodes of
      interstitial pneumonitis was investigated, using immunocytochemical methods.
      Results were compared with those from seven normal volunteers. The results showed
      that patients with pneumonitis had significantly higher numbers of total cells in
      BALF than normals but reduced proportions of macrophages, although the absolute
      numbers were unchanged. Of the cells present which were morphologically
      macrophages, there were raised proportions of both RFD1+ cells (interdigitating
      cells) and RFD7+ cells (mature macrophages) in patients compared with normals,
      but expansion of these two subsets could be explained, in part, by a significant
      increase in cells positive for both markers (42% in patients compared with 9% in
      normals). Proportions of cells with the monocyte phenotype (CD14+, UCHM1) were
      also significantly raised in patients with pneumonitis (17% compared with 6% in
      normals). These patients, however, had significantly reduced proportions of
      macrophage-like cells which were positive for the DR antigen (Class II major
      histocompatibility complex (MHC) antigen) (47% compared with 88% in normals), and
      this abnormality was greater still in patients who died from pneumonitis (40%)
      compared with those who survived (52%). The results of this study indicate a
      breakdown of local immunoregulation, thus contributing to the high incidence of,
      and mortality from, opportunistic pulmonary infections in this group.

PMID- 8287946
TI  - Bronchoalveolar lavage phospholipid abnormalities in HIV-infected patients.
AB  - Our aim was to evaluate the quality of pulmonary surfactant, a nonspecific
      defence system, during the course of human immunodeficiency virus) infection.
      Protein and phospholipid composition were determined in 127 bronchoalveolar
      lavage (BAL) fluids from 89 HIV seropositive patients (54 acquired immune
      deficiency syndrome (AIDS), 35 non-AIDS) and 11 healthy controls. In all of the
      HIV BAL samples, biochemical abnormalities were found. In subjects with pulmonary
      infection or Kaposi's sarcoma, the phospholipid/protein ratio was decreased,
      mainly because of elevated protein levels (15.8 and 20, respectively, vs 7.2
      mg.100 ml-1 for controls, p < 0.05). In subjects without obvious pulmonary
      involvement, phospholipid was decreased (1.3 +/- 0.2 vs 2.9 +/- 0.3 mg.100 ml-1
      for controls, p < 0.001), whereas the protein was not altered. Phospholipid
      composition was also altered: the phosphatidylcholine percentage was decreased,
      whilst the other main phospholipids were increased. We conclude that the alveolar
      lining is altered, whatever the stage of HIV disease. In most patients, it
      results from an increase of vascular permeability, with an influx of serum
      proteins. However, changes in phospholipid composition suggest that, in some
      cases, surfactant is also altered.

PMID- 8287947
TI  - Human bronchial epithelial cell dysfunction following in vitro exposure to
      nitrogen dioxide.
AB  - Nitrogen dioxide (NO2), is a major air pollutant, that causes bronchoconstriction
      and bronchial hyperreactivity, and may also lead to damage and inflammation of
      the airway epithelium. We have cultured human bronchial epithelial cells and
      investigated the effect of exposure to NO2, for 20 min on epithelial cell
      membrane integrity and function in vitro. Epithelial cell membrane damage and
      permeability were assessed by release of 51Cr from prelabelled cells, and
      movement of 14C-labelled bovine serum albumin (BSA) across the bronchial
      epithelial cell monolayers. Ciliary beat frequency (CBF) of the cells was
      monitored by the analogue contrast enhancement technique, and arachidonic acid
      (AA) metabolism was investigated by analysis of radiolabelled AA metabolites
      generated from cultures prelabelled by incubation with [3H]-arachidonic acid.
      Exposure to 400 and 800 parts per billion (ppb) NO2 significantly increased the
      release of 51Cr from 0.9 +/- 0.4%, in control cultures exposed to 5% CO2 in air,
      to 9.7 +/- 3.2% and 13.9 +/- 3.5%, respectively. Similarly, NO2 also
      significantly increased the movement of 14C-BSA across the epithelial monolayers
      from 1.3 +/- 0.2%, in control cultures, to 2.7 +/- 0.2%, 3.8 +/- 0.4% and 5.1 +/-
      0.5%, respectively, in cultures exposed to 100, 400 and 800 ppb NO2. Although NO2
      attenuated the CBF of the cells at all concentrations investigated, this was
      significant only at the concentration of 2,000 ppb NO2.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8287948
TI  - Selenium deficiency augments the pulmonary toxic effects of oxygen exposure in
      the rat.
AB  - Selenium (Se) is a component of the antioxidant enzyme glutathione peroxidase
      (GSHPx). We wanted to determined whether Se deficiency predisposes to pulmonary
      O2 toxicity. Sixteen weanling rats were fed a Se-free diet (Se-). Sixteen rats
      fed the same diet had drinking water supplemented with 400 micrograms.l-1 sodium
      selenite (Se+). After 5 weeks, rats were killed after exposure to either 95% O2
      or air for 36 h. Se concentration in blood, lung, liver, heart, muscle and
      spleen, and blood GSHPx activity were higher in Se+ than in Se- groups. Pulmonary
      oedema developed in both O2-exposed groups, but was more severe in Se-O2 group
      than in the Se+O2 group, as judged by the presence of pleural effusions (7 out of
      8 versus 0 out of 8), elevated lavage protein concentration (173 +/- 17 versus
      120 +/- 14 micrograms.ml-1), and higher wet/dry weight ratio (W:D) (5.8 +/- 0.07
      versus 5.4 +/- 0.07). W:D correlated inversely with lung Se content in O2-exposed
      rats. Both O2-exposed groups had a reduction in the amount of less aggregated
      lavage phospholipid (PL) compared with the Se+air group. However, the Se-O2 group
      had increased total PL, because of an increase in more aggregated PL. We conclude
      that Se deficiency exacerbates pulmonary injury in O2-exposed rats, and that O2
      toxicity is associated with an altered physical form of alveolar surfactant.

PMID- 8287949
TI  - Production of acute bronchiolitis in guinea-pigs by human respiratory syncytial
      virus.
AB  - Respiratory syncytial virus (RSV) is the most important cause of acute
      bronchiolitis in young children, and is implicated in the pathogenesis of
      paediatric asthma. The present studies were designed to develop a model of acute
      RSV bronchiolitis in young guinea-pigs, that could be used to study the
      mechanisms of the acute bronchiolitis and its sequelae. Anaesthetized, one month
      old guinea-pigs received either 4 x 10(3) plaque forming units of Long strain
      human RSV or uninfected cell culture medium intranasally. Bronchiolar
      inflammation was assessed 6 days (n = 10 RSV-inoculated; n = 10 controls) and 14
      days (n = 10 RSV-inoculated; n = 9 controls) postinoculation using a
      semiquantitative histological scoring system. Viral replication within the lung
      was evaluated by culture, and the intrapulmonary distribution of viral antigens
      was evaluated by immunohistochemistry. The RSV-inoculated group showed
      histological evidence of acute bronchiolitis 6 days after inoculation, which
      subsided by Day 14. Replicating virus was cultured from the lungs of 9 out of 10
      RSV-inoculated animals on Day 6, and 2 out of 10 animals on Day 14, with no
      growth from control animals. Viral antigens were identified primarily within
      airway epithelial cells on Day 6, and within alveolar macrophages on Day 14.
      Intranasal inoculation of human RSV into guinea-pigs provides a model of acute
      RSV bronchiolitis that may facilitate the study of both the pathogenesis of acute
      infection and the possible role of RSV in the subsequent development of
      nonspecific bronchial hyperresponsiveness in children.

PMID- 8287950
TI  - Phrenic nerve stimulation at the bedside in children; equipment and validation.
AB  - There is evidence that early diagnosis of postoperative phrenic nerve damage may
      improve outcome, by allowing early surgical treatment, in children following
      cardiac surgery. This has prompted the development of a simple method for
      measuring phrenic nerve latency at the bedside in children. We have evaluated the
      reproducibility of measurements made with this system in 11 children (4 months to
      13 yrs) admitted for routine surgery or cardiac catheterizations, and have
      assessed the various components of variability inherent in the measurement of
      phrenic nerve latency. The overall variability of the phrenic nerve latency with
      this technique (95% confidence interval) is approximately +/- 1 ms, and
      differences greater than this between measurements are likely to reflect a real
      change in phrenic nerve function. Our results indicate that the bedside technique
      should be a useful method of the objective assessment of phrenic nerve function
      in children recovering from cardiac surgery.

PMID- 8287951
TI  - Early assessment of diaphragmatic dysfunction in children in the ITU: chest
      radiology and phrenic nerve stimulation.
AB  - Diaphragmatic dysfunction is a common postoperative complication of cardiac
      surgery in children, with important effects on respiratory morbidity. Its early
      diagnosis, followed by prompt surgical intervention, has been shown to reduce
      morbidity. However, the commonest method of diagnosis, based on hemi
      diaphragmatic elevation on the chest radiograph, may be less accurate than direct
      techniques for assessing phrenic nerve function. We have compared
      electrophysiological and radiological diagnoses of diaphragmatic abnormality in
      100 children (aged 3 days to 17.5 yrs) undergoing cardiac surgery, looking at
      respiratory morbidity as assessed by the duration of ventilation, the time spent
      on the cardiac intensive care unit (CICU), and the requirement for reintubation.
      Despite showing good reproducibility, radiological diagnosis was neither
      sensitive nor specific in identifying patients with electrophysiological phrenic
      nerve damage. Analysis of the measures of outcome supported the
      electrophysiological technique. Patients with electrophysiological evidence of
      damage had a longer duration of ventilation, spent longer on the CICU, and had a
      greater incidence of reintubation than either radiologically abnormal or "normal"
      patients. Chest X-rays are not a good method for diagnosing phrenic nerve damage
      in the early postoperative period in children. If early diagnosis is needed, then
      direct assessment of phrenic nerve function, such as the measurement of phrenic
      latency, may be a better technique.

PMID- 8287952
TI  - Frequency dependence of elastance and resistance in ventilated children with and
      without the chest opened.
AB  - Measurements of respiratory mechanics in mechanically-ventilated children are
      potentially useful for understanding the pathogenesis and progress of diseases
      resulting in respiratory failure. Measurement techniques that can be simply and
      noninvasively employed model the respiratory system as a single compartment. The
      frequency dependence of elastance and resistance, both of the total respiratory
      system and of the lungs, was investigated in eight children (aged 2-56 months)
      undergoing open-heart surgery. The children were studied whilst anaesthetized,
      paralysed and mechanically-ventilated. Dynamic elastance (Ers) and resistance
      (Rrs) of the respiratory system and of the lung (EL, RL) were calculated using a
      multilinear regression technique, with the chest wall intact, prior to the
      commencement of surgery, and with the chest wall opened via a mid-line
      sternotomy. Measurements were repeated after brief (60 s) changes in ventilation
      frequency. The total respiratory system and the lungs demonstrated frequency
      dependent behaviour, with elastance increasing and resistance decreasing with
      frequency. The pattern of the frequency-dependent behaviour was essentially the
      same, whether the chest wall was intact or opened, suggesting that the chest wall
      was not solely responsible for this behaviour in these children. These data are
      consistent with a linear viscoelastic model containing a Kelvin body. When using
      measurements of respiratory mechanics to follow the progress of respiratory
      disease in mechanically-ventilated children, this frequency-dependent behaviour
      must be taken into account.

PMID- 8287953
TI  - Determination of peak expiratory flow.
AB  - It is still unknown whether peak expiratory flow (PEF) is determined by "wave
      speed" flow limitation in the airways. To investigate the influences of airway
      mechanical properties on PEF, five healthy adults performed maximal forced
      expiratory effort (MFEE) manoeuvres, in the standard manner and following
      breathholds at total lung capacity (TLC) of 2 s and 10 s. Oesophageal pressure
      (Poes) was measured as an index of respiratory effort. Subjects also performed a
      MFEE following a 10 s breathhold during which intrathoracic pressure was
      voluntarily raised by a Valsalva manoeuvre, which would increase transmural
      pressure and cross-sectional area of the extrathoracic airway. Additional MFEEs
      were performed with the neck fully flexed and extended, to change longitudinal
      tracheal tension. In separate studies, PEF was measured with a spirometer and
      with a pneumotachograph. Breathholds at TLC (2 s and 10 s), and neck flexion
      reduced PEF by a mean of 9.8% (SD 2.9%), 9.6% (SD 1.6%), and 8.7% (SD 2.8%),
      respectively, when measured with the spirometer. The same pattern of results was
      seen when measured with the pneumotachograph. These reductions occurred despite
      similar respiratory effort. Voluntarily raising intrathoracic pressure during a
      10 s breathhold did not reverse a fall in PEF. MFEE manoeuvre with neck extension
      did not result in an increase in PEF, the group mean % changes being -3.0% (SD
      5.0%). We conclude that these results do not allow the hypothesis that "wave
      speed" (Vws) is reached at PEF to be rejected. A breathhold at TLC could increase
      airway wall compliance by allowing stress-relaxation of the airway, thus reducing
      the "Vws" achievable.

PMID- 8287954
TI  - Reversible hypercapnia in acute exacerbations of chronic obstructive pulmonary
      disease (COPD).
AB  - We prospectively studied emergency hospitalizations due to acute exacerbations of
      chronic obstructive pulmonary disease (COPD) among 74 hypercapnic patients, in
      order to determine factors which predict reversal to normocapnia as a result of
      therapy. Clinical, arterial blood gas and pulmonary function data on presentation
      were compared to predischarge values among those 58 patients who survived the
      admission. Patients were divided into those who reverted to normocapnia
      (reversible, 40% of surviving patients), and those who remained hypercapnic
      (chronic, 60% of surviving patients). Reversible patients had higher admission
      arterial oxygen tension (PaO2) levels than those with chronic hypercapnia (6.4 +/
      1.3 kPa (mean +/- SD), as compared to 5.7 +/- 1.1 kPa) better pulmonary function
      (forced expiratory volume in one second (FEV1) 35 +/- 16% predicted, as compared
      to 26 +/- 7.9), and a lower prevalence of cor pulmonale (30% as compared to 63%
      of patients). No admission variable(s) distinguished individual patients as
      reversible or chronic hypercapnic, and, in particular, admission arterial carbon
      dioxide tension (PaCO2) and pH levels were similar in both groups. Furthermore,
      there were no differences between survivors and those 16 patients who died during
      the admission, apart from a higher urea level among those who died. These
      findings suggest that reversible patients have milder underlying disease than
      those with chronic hypercapnia. Our data establish the high prevalence of
      reversible hypercapnia among patients hospitalized with exacerbations of COPD,
      and, furthermore, indicate that patients who are normocapnic in the stable state
      can develop similar levels of hypercapnia during exacerbations as those with
      chronic hypercapnia.

PMID- 8287955
TI  - Habitual snoring as a risk factor for acute vascular disease.
AB  - We wanted to assess habitual snoring as a credible risk factor for acute vascular
      disease, mainly stroke and myocardial infarction. The patients selected for the
      study had been admitted to the hospital through the emergency department, and
      were evaluated by means of multidimensional interviews and clinical records: 164
      had acute cerebrovascular disease, and 136 cardiovascular disease; 330 patients
      with nonvascular disease were the controls. The evaluation showed 48% of vascular
      disease patients to be habitual snorers, but only 30% of the controls; the
      difference was statistically significant. Compared with the controls, in the
      cerebrovascular patients the risk (odds ratio) associated with habitual snoring
      was significantly increased, and of the same order as the risk associated with
      age over 65 yrs, male gender, diabetes mellitus, and dyslipidaemia; whilst the
      risk associated with hypertension was higher. In the cardiovascular patients, the
      risk associated with habitual snoring was again significantly increased and of
      the same order as the risk associated with male gender, body mass index > 29
      (kg.m-2), dyslipidaemia, heavy smoking, excessive alcohol intake and
      hypertension. A logistic regression analysis, entering the variables in the
      following order: age, gender, body mass index, diabetes, dyslipidaemia, smoking,
      alcohol, hypertension, and habitual snoring, showed that habitual snoring carries
      a significant risk factor for stroke and myocardial infarction, even after
      adjusting for other factors. Since habitual snoring carries a definite risk for
      acute vascular disease, we conclude that inquiring about it should become routine
      practice.

PMID- 8287956
TI  - Relationship between exercise capacity and the severity of emphysema as
      determined by high resolution CT.
AB  - We investigated the relationship between exercise capacity or exercise-induced
      hypoxaemia and the severity of pulmonary emphysema in 20 patients with pulmonary
      emphysema. The patients underwent pulmonary function tests, high resolution
      computed tomography and incremental treadmill exercise testing. Computed
      tomography scans were obtained at four levels in the lungs, and emphysema scores
      were determined by the visual assessment of low attenuation areas as a measure of
      the severity of parenchymal destruction. The emphysema score correlated
      significantly with diffusing capacity (r = -0.69) in the pulmonary function
      tests. Among the exercise test parameters, the emphysema score correlated
      significantly with the total distance walked (r = -0.74), with maximal oxygen
      consumption (VO2max) (r = -0.77), with arterial oxygen tension (PaO2) at rest (r
      = -0.50) and at the maximum workload (r = -0.58), and with the decrement of
      arterial oxygen tension per litre of oxygen consumed (r = -0.64). These results
      suggest that exercise capacity and exercise-induced hypoxaemia are related to the
      extent of destruction of lung parenchyma in patients with pulmonary emphysema.

PMID- 8287957
TI  - Effect of pulmonary hypertension on gas exchange.
AB  - This paper reviews the effects of pulmonary artery hypertension on gas exchange
      by exploring three different issues, namely: 1) how does gas exchange behave in
      diseases characterized by increased vascular tone (primary pulmonary hypertension
      (PPH), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary
      fibrosis (IPF)) or decreased vascular tone ("hepatopulmonary syndrome"); 2) how
      does exercise, as a non-pharmacological tool of increasing pulmonary blood flow,
      modify gas exchange in these diseases; and 3) how do several drugs that lower
      (vasodilators) or increase (almitrine) the active component of pulmonary
      hypertension interact with gas exchange. Available data show that: 1) in PPH a
      high pulmonary vascular tone enhances gas exchange and when it is lowered, either
      by oxygen or vasodilators, ventilation perfusion (VA/Q) distributions
      deteriorate; 2) in COPD a lowered (vasodilators) or augmented (almitrine) active
      vascular tone is almost invariably paralleled by a deterioration or enhancement
      of ventilation-perfusion matching, respectively; 3) in IPF an adequate active
      response of the pulmonary vasculature is essential to maintain gas exchange, both
      at rest and during exercise; and 4) in patients with liver cirrhosis a low
      pulmonary vascular tone induces an abnormal VA/Q distribution. In summary, these
      data show that any situation and/or therapeutic intervention that lowers the
      active vascular tone deteriorates VA/Q relationships and vice versa. The final
      effect of pulmonary vascular tone on arterial oxygen tension (PaO2) is less
      predictable. The reason for this uncertainty is that the actual PaO2 value
      depends on the interplay of the intra- and extrapulmonary factors that control
      gas exchange in humans, and not only on the degree of VA/Q mismatching.

PMID- 8287958
TI  - Pulmonary immune cells in health and disease: lymphocytes.
AB  - Immunological defence mechanisms of the lung are provided by several different
      types of immunocompetent cell. Among these, the most important are lymphocytes,
      alveolar macrophages and neutrophils. This review focuses mainly on the pattern
      of physiological activities of pulmonary lymphocytes in the local host defences.
      The article provides an overview of the events leading to the recruitment, homing
      and activity of lymphocytes in the lower respiratory tract. The pathways through
      which the pulmonary lymphoid system recognizes, destroys and contributes to
      removing potentially harmful inhaled antigenic materials are also briefly
      discussed. The final section of the article highlights the pathogenetic role
      envisaged for lymphoid cells in disease states, in the context of the known
      biology of these cells.

PMID- 8287959
TI  - Investigative use of fibreoptic bronchoscopy for local airway challenge in
      asthma.
AB  - Local airway challenge has advantages over inhalation bronchial challenge as the
      response of the airway can be restricted and directly observed. It has been
      safely performed in subjects with mild or moderate asthma, either by the direct
      instillation of challenge solution to the selected segmental airways via a
      bronchoscope, or delivered to an airway segment isolated with a double-balloon
      catheter. However, these techniques carry potential complications, such as
      generalized wheeze, and due care is required in selection of subjects. Most
      investigators have used the method for studying the airway events following
      allergen challenge. Others have studied the airway changes following challenge
      with non-allergen provocation agents, such as hypertonic saline, adenosine 5'
      monophosphate and cold dry air. The method has helped to define changes in the
      inflammatory cells and mediators in relation to early and late airway responses
      to allergen. Similarly, study of airway events following local challenge with
      hypertonic solution has provided useful knowledge in understanding the mechanisms
      of exercise-induced asthma. With more experience and an improved margin of
      safety, it will be possible to study local changes in airway physiology following
      local airway challenge. Finally, the techniques also have potential use for
      studying the airway events following provocation with a wide range of agents of
      potential relevance to the pathogenesis of asthma.

PMID- 8287960
TI  - Acute interstitial pneumonitis induced by carbamazepine.
AB  - A 62 year old man treated with carbamazepine for 3 months developed eczema and
      acute interstitial pneumonitis. A lymphocyte-stimulation test was reactive to
      carbamazepine. Withdrawal of the drug resulted in prompt improvement. Only 10
      cases of this type of drug-induced lung disease have previously been reported.

PMID- 8287961
TI  - Congenital oesophageal respiratory tract fistula presenting in adult life.
AB  - Congenital oesophageal respiratory tract fistula presenting in adult life is
      rare. A tracheo-oesophageal and a broncho-oesophageal fistula presenting in a 22
      year old female and 68 year male, respectively, are described. In both, symptoms
      of chronic recurrent pulmonary suppuration were initially attributed to
      alternative aetiologies, resulting in diagnostic delay and inappropriate
      management. Correct diagnosis was established by flexible bronchoscopy and
      oesophageal contrast studies. Surgical division of fistulae resulted in complete
      symptom resolution.

PMID- 8287962
TI  - Guidelines on standardized challenge testing for airway hyperresponsiveness.

PMID- 8287963
TI  - Models for analysis of longitudinal data.

PMID- 8287964
TI  - Monomeric and dimeric forms of cholesterol esterase from Candida cylindracea.
      Primary structure, identity in peptide patterns, and additional
      microheterogeneity.
AB  - Cholesterol esterase from Candida cylindracea was separated into two fractions,
      corresponding to a dimeric and a monomeric form. Fingerprint analysis after
      lysine cleavages shows identical patterns, suggesting lack of primary
      differences. Crystals obtained from the two proteins differ and suggest the
      possibility of an equilibrium between the two forms, influenced by the substrate
      cholesterol linoleate, which appears to stabilize the more active, dimeric form.
      All crystals have dimers as the asymmetric unit. The primary structure of the
      enzyme was determined at the peptide level and shows only one difference, Leu-350
      instead of Ile, from a DNA-deduced amino acid sequence, and conservation of
      features typical for cholesterol esterases characterized.

PMID- 8287965
TI  - The role of the autoinhibitory domain in differential metal ion activation of
      calmodulin-stimulated phosphatase.
AB  - Metal ion activators, Ni2+ and Mn2+, have been suggested to induce different
      conformations of calmodulin (CaM)-stimulated phosphatase. In the present study,
      an autoinhibitory domain previously implicated in the conformation transition of
      CaM stimulation of the phosphatase is shown to participate in defining the
      differential metal ion activation. A proteolytic derivative of the phosphatase
      deleted from the autoinhibitory domain displayed CaM-independent Mn(2+)
      stimulated activity which was about 4-times that of the CaM-stimulated activity
      of the native enzyme. The Ni(2+)-stimulated activity of the derivative, on the
      other hand, retained slight CaM-dependence, and the CaM-stimulated activity was
      90% of that of the native enzyme. A synthetic peptide corresponding to the
      autoinhibitory domain could inhibit the Mn(2+)-stimulated activity of the
      phosphatase derivative by 80%, but had little effect on the Ni(2+)-stimulated
      activity.

PMID- 8287966
TI  - Recombinant soluble urokinase receptor as a scavenger for urokinase-type
      plasminogen activator (uPA). Inhibition of proliferation and invasion of human
      ovarian cancer cells.
AB  - A recombinant soluble human urokinase receptor comprising amino acids 1-277 was
      cloned and transfected into CHO cells. The mutant protein (rec-uPAR277), purified
      from the CHO cell supernatant by affinity chromatography on immobilized urokinase
      (uPA), in a four-fold excess, completely abolished the binding of FITC-labeled
      pro-uPA to the human ovarian cancer cell line, OV-MZ-6. This invasive and
      tumorigenic cancer cell line expresses uPA, its inhibitor PAI-1, and the high
      affinity receptor for uPA, uPAR. Rec-uPAR277 significantly reduced the
      proliferation of OV-MZ-6 cells in a concentration-dependent manner without
      altering the viability of the cells. Invasion of OV-MZ-6 cells tested in an in
      vitro Matrigel invasion assay was inhibited by rec-uPAR277 up to 75%. In
      conclusion, these results demonstrate that rec-uPAR277 can function as a
      scavenger for uPA in vitro by inhibiting proliferation and invasion of human
      cancer cells.

PMID- 8287967
TI  - Assembly of Alzheimer-like filaments from full-length tau protein.
AB  - The principal fibrous component of neurofibrillary pathology in Alzheimer's
      disease, the paired helical filament, is formed from hyperphosphorylated
      microtubule-associated protein tau. Here we show that recombinant tau protein
      either in a non-phosphorylated state or following phosphorylation with brain
      extract can be assembled in vitro into filaments resembling those seen in
      Alzheimer's disease.

PMID- 8287968
TI  - Conformations of the alternating (C-T)n sequence under neutral and low pH.
AB  - The structures of the (C-T)n sequence at two different pHs have been analyzed by
      500 MHz 2D-NMR using a modified DNA decamer d(CT[m5C]TCU[m5C]UCT) as a model
      system. The chemical modifications serve to perturb the monotonous C-T repeat,
      and consequently to yield a better chemical shift dispersion. The results
      reinforce our earlier suggestion that there are three major pH-dependent
      conformational species: two antiparallel-stranded (APS) duplexes at pH 7 and pH
      3, and a different structure near pH 5. Structural refinement of the decamer
      duplexes at pH = 7.5 and pH = 2.9 using 2D-NOE data suggests that the C:T or C+:T
      base pairs are continuously stacked. Exchangeable proton NMR spectra at pH 7.5
      and pH 2.9 are consistent with C:T or C+:T base pairing schemes in which a water
      molecule bridges the two bases.

PMID- 8287969
TI  - Elucidation of the poly-L-proline binding site in Acanthamoeba profilin I by NMR
      spectroscopy.
AB  - The multifunctional protein profilin is one of the most abundant proteins in the
      cytoplasm and is thought to regulate actin assembly and the phosphoinositide
      signaling pathway. Profilin binds to several different ligands including actin,
      poly-L-proline, and the head groups of polyphosphoinositides. Knowledge of
      profilin/ligand interactions is important for understanding the physiology of
      profilin in the cell. As a first step in the characterization of profilin/ligand
      complexes, we have studied a profilin/poly-L-proline complex in solution using
      high resolution NMR spectroscopy. Analysis of profilin NOE's and chemical shift
      data indicates that the protein secondary structure is conserved upon binding to
      poly-L-proline and that the binding site is located between the N- and C-terminal
      helices in a region rich in highly conserved aromatic sidechains. This site is
      adjacent to the proposed binding site for actin. In addition, the rate constant
      for dissociation of the complex is found to be 1.6 +/- 0.2 x 10(4) s-1.

PMID- 8287970
TI  - Cloning and sequence analysis of a cDNA encoding rice glutaredoxin.
AB  - A full-length cDNA clone (RASC8) encoding glutaredoxin (thioltransferase) was
      isolated from a cDNA library of an aleurone layer prepared from a developing seed
      of rice (Oryza sativa L.). RASC8, 568bp in length, contained an ATG codon and two
      possible polyadenylation signals, and encoded 112 amino acid residues. Cys-Pro
      Phe-Cys, which is the active site and a highly conserved sequence among
      thioltransferases, was found in the deduced amino acid sequence. RASC8 was
      introduced into an expression vector pMALc2 and the translated product possessed
      thioltransferase activity.

PMID- 8287972
TI  - Noncanonical Oct-sequences are targets for mouse Oct-2B transcription factor.
AB  - We have suggested a random modification method for determining preferable binding
      sites of a DNA-binding protein and applied this method to the Oct-2B
      transcription factor. Our results indicate that the Oct-2B protein interacts with
      canonical oct sequence ATGC/TAAAT and degenerated sequences which contain TAAT
      motif in the binding site. We have determined nucleotides in the binding sites,
      involved in the DNA-protein interaction, and the equilibrium dissociation
      constants Kd for these sequences. These data show that a much greater number of
      potential targets for Oct proteins exist on DNA and changed our view on the gene
      expression regulation by this protein factor.

PMID- 8287971
TI  - Positive and negative regulatory elements are involved in transcriptional control
      of the rat glucokinase gene in the insulin producing cell line HIT M2.2.2.
AB  - Nested deletion mutants of the 5' flanking region of the beta-cell transcription
      unit of the rat glucokinase gene (r beta GK) were fused to the CAT-reporter gene.
      Transient expression studies in HIT M2.2.2 and BHK21 cells revealed a distal
      (upstream of -359) and a proximal promoter region (between -278/-49) harbouring
      positive and negative regulatory elements. DNaseI footprinting revealed three
      protected areas between nucleotides -190 and -60. DNA-elements playing a crucial
      role in transcriptional control of the insulin genes (IEB- and CT-motifs) have
      been detected within the proximal promoter region and contribute to beta-cell
      specific gene regulation. 3' deletion analysis revealed that DNA-elements located
      downstream from transcription initiation sites (up to +123) contribute to
      transcriptional regulation.

PMID- 8287973
TI  - Nitric oxide donor GEA 3162 inhibits endothelial cell-mediated oxidation of low
      density lipoprotein.
AB  - The effect of a nitric oxide (NO) donor GEA 3162 on the endothelial cell (EC)
      mediated oxidation of low density lipoprotein (LDL) was studied. In comparison to
      LDL incubated with EC without GEA 3162, the presence of GEA 3162 inhibited LDL
      oxidation by EC, as indicated by the following findings. (a) The degradation rate
      of LDL in macrophages was reduced to control levels. (b) The electrophoretic
      mobility of LDL decreased in a dose-dependent manner. (c) The concentrations of
      thiobarbituric acid-reactive substances and hydroperoxide-derived hydroxy fatty
      acids were lower. (d) The breakdown of apolipoprotein B was reduced. The results
      indicate that GEA 3162 prevents EC-mediated oxidation of LDL.

PMID- 8287974
TI  - Regulation of the 28 kDa heat shock protein by retinoic acid during
      differentiation of human leukemic HL-60 cells.
AB  - Dysregulation of hematopoietic cellular differentiation contributes to
      leukemogenesis. Unfortunately, relatively little is known about how cell
      differentiation is regulated. Considering that heat shock proteins (hsp) and
      specifically the small hsps have been increasingly linked to growth regulation,
      we sought to determine whether the mammalian small hsp (hsp28) is a growth
      regulatory candidate during hematopoietic cell differentiation. Because of its
      effects on cell growth and differentiation and its increasing clinical use as a
      differentiating agent, we examined the effect of retinoic acid (RA) on hsp28
      during differentiation of the human leukemic HL-60 cell line. Although hsp28 was
      constitutively expressed at low levels in untreated HL-60 cells, steady state
      hsp28 protein increased transiently, concomitant with the onset of G1 cell cycle
      arrest. Furthermore, hsp28 phosphorylation transiently increased within one hour
      following treatment with RA. Interestingly, in contrast to other differentiating
      agents the induction of hsp28 by RA was post-transcriptionally mediated with
      hsp28 protein and mRNA being discordantly regulated. These observations
      underscore the complex regulation of hsp28 by RA during granulocytic
      differentiation of human leukemic cells and indicate hsp28 as an intermediary in
      the pathway through which retinoids exert their growth and differentiative
      effects.

PMID- 8287975
TI  - Ribosome-messenger recognition in the absence of the Shine-Dalgarno interactions.
AB  - In an attempt to understand how Escherichia coli ribosomes recognize the
      initiator codon on mRNAs lacking the Shine-Dalgarno (SD) sequence, we have
      studied 30S initiation complex formation in extension inhibition (toeprinting)
      experiments using (-SD)mRNAs which are known to be reliably translated in E.
      coli: the plant viral messenger A1MV RNA 4 and two chimaeric mRNAs coding for
      beta-glucuronidase (GUS) and bearing the 5'-untranslated sequence of TMV RNA
      (omega) or the omega-derived sequence (CAA)n as 5'-leaders. Ribosomal protein S1
      and IF3 have been found to be indispensable for translational initiation. Protein
      S1 appears to be a key recognition element. S1 binds to sequences within the
      leaders of (-SD)mRNAs thus providing their affinity to E. coli ribosomes.

PMID- 8287976
TI  - Contribution of salt bridge in the protease inhibitor SSI (Streptomyces
      subtilisin inhibitor) to its inhibitory action.
AB  - The tertiary structure of proteinaceous protease inhibitors is considered to be
      maintained by various interactions in the molecule that prevent degradation by
      protease. In this study, the Arg29 of Streptomyces subtilisin inhibitor (SSI)
      forming a salt bridge with the carboxyl group of carboxyl-terminal Phe113 was
      replaced with Ala, Met or Lys by cassette mutagenesis to clarify the role of
      Arg29 in the function of SSI. The inhibitory activity of each mutated SSI
      decreased with increasing incubation time after mixing with subtilisin,
      indicating that the SSI was changed into a temporary inhibitor upon mutation.
      This decrease was shown by SDS polyacrylamide gel electrophoresis to be due to
      cooperative degradation of the mutated SSI by subtilisin. In addition, the
      denaturation temperature of the Ala or Met mutant was decreased by ten degrees
      and that of the Lys mutant by 1.5 degrees, suggesting that the destabilization of
      SSI may be related to its temporary inhibition. Thus, interaction in the protease
      inhibitor molecule for maintaining the tertiary structure, such as that of Arg29
      in SSI, was shown to be required for the inhibitory action.

PMID- 8287977
TI  - Molecular cloning of a novel protein-tyrosine phosphatase containing a membrane
      binding domain and GLGF repeats.
AB  - A full-length cDNA encoding a novel cytosolic protein-tyrosine phosphatase (PTP),
      PTP-BAS, was cloned from human basophils. Due to in-frame deletions in the coding
      region, PTP-BAS exists in three isoforms: 7,455 bp (2,485 aa) for type 1, 7,398
      bp (2,466 aa) for type 2 and 6,882 bp (2,294 aa) for type 3. All three isoforms
      contain a single PTP catalytic domain at the carboxyl termini as well as two
      distinct structural sequences. Amino terminal sequences of 300 amino acids are
      homologous to membrane-binding domains of cytoskeleton-associated proteins. Three
      90 amino acid internal repetitive sequences are homologous to the GLGF repeats
      found in guanylate kinase proteins. PTP-BAS was expressed in various human
      tissues, especially highly in the kidney and lung. Interestingly, the BAS mRNA
      level in the fetal brain was remarkably high.

PMID- 8287978
TI  - Polarity conserved positions in transmembrane domains of G-protein coupled
      receptors and bacteriorhodopsin.
AB  - The polarity of residues at certain positions in the transmembrane domains of G
      protein coupled receptors (GPCR) is found to be conserved, and to indicate the
      pattern of specific helix-helix packing of the helices. A concept of polarity
      conserved positions (PCP) is proposed to describe this conserved property, and is
      applied to obtain insight into the structural features of the transmembrane
      proteins. The common pattern of PCPs for GPCRs indicates that they share a
      similar packing arrangement of their transmembrane helix bundles. For proteins in
      the bacteriorhodopsin family the PCP pattern suggests a common packing
      arrangement that differs from that of GPCRs, in agreement with experimental data.
      This difference in the packing arrangement underscores the shortcomings of a BR
      template for the construction of molecular models of GPCRs.

PMID- 8287979
TI  - Site-specific labelling of the oligosaccharide chains of antibodies.
AB  - This paper presents a new method for site-specific labelling of antibodies
      employing enzymatic reactions without oxidizing or reducing agents. IgG was first
      treated with immobilized sialidase from Clostridium perfringens to cleave bound
      NeuAc. CMP-9-deoxy-9-salizoyl-NeuAc, an activated sialic acid analogue, was
      labelled with 131I via the iodogen-method in high yields (> 95%). Then the
      oligosaccharide chains of antibodies were labelled yield with the radioactive
      NeuAc analogue by transfer using alpha-2,6-sialyltransferase from rat liver in
      50%.

PMID- 8287980
TI  - A comparative approach to anterior segment dysgenesis.
AB  - The role of animal models in our developing understanding of anterior segment
      dysgenesis is outlined. Research in avian models shows the importance of the
      neural crest in the development of the anterior segment and the failure of terms
      such as anterior segment cleavage adequately to describe the embryology of this
      area. Study of the anatomical differences between the anterior segment of the
      primate and that of the sub-primate mammal explains the differences seen in the
      dysplastic changes occurring in the iridocorneal angle in man and those occurring
      in sub-primate mammals such as the rabbit or the dog. Such work gives an improved
      understanding of congenital lesions seen ophthalmologically in man as well as
      those encountered in veterinary ophthalmology.

PMID- 8287981
TI  - Excimer laser photorefractive keratectomy for myopia: 12 month follow-up.
AB  - A prospective study of excimer laser photorefractive keratectomy was performed
      with the aim of correcting a range of myopic errors between -1.00 and -10.00
      dioptres. Corneal healing was monitored through the first post-operative year by
      serial assessments of refraction, contrast sensitivity, corneal haze, pachymetry
      and keratometry. Eighty-one patients were recruited for the study. At 12 months
      81% were within +/- 1.00 dioptre of desired emmetropia and with unaided vision of
      6/12. Contrast sensitivity was found by Pelli-Robson assessment to be reduced
      throughout the 12 months and regression analysis predicted recovery by 2 years.
      At 12 months, however, only 15% of patients were found to have lost a single line
      of best corrected Snellen acuity. Predictability of results was found to be
      greatest for initial errors less than -4.00 dioptres. No serious complications
      were observed during the follow-up period, but refraction had not stabilised in
      all cases and patients remain under review.

PMID- 8287982
TI  - The management of post-keratoplasty astigmatism by post-operative adjustment of a
      single continuous suture.
AB  - Penetrating keratoplasty was performed in 39 consecutive patients. A 16 bite 10-0
      nylon continuous suture was used. Post-operatively, the suture was adjusted to
      reduce astigmatism, as determined by refraction, keratoscopy and keratometry.
      Suture adjustment was performed if astigmatism was over 4 dioptres (D). The
      suture was tightened in the flatter meridian and loosened in the steeper
      meridian. Twenty-one patients had suture adjustment performed. Prior to
      adjustment, mean (+/- standard deviation) astigmatism measured 6.33 +/- 1.38 D.
      Following adjustment, mean astigmatism was significantly reduced to 2.69 +/- 1.14
      D (p < 0.0001). The average final astigmatism for the entire group was 2.66 +/-
      1.12 D. The use of a continuous adjustable suture in penetrating keratoplasty
      significantly reduced the post-operative astigmatism in a group of patients
      undergoing penetrating keratoplasty.

PMID- 8287983
TI  - Limbal transplantation in the management of chronic contact-lens-associated
      epitheliopathy.
AB  - We describe the clinical management of 6 patients who developed a chronic corneal
      epitheliopathy 1-18 years after commencing soft contact lens wear. All had a
      history of exposure to thiomersal in contact lens fluids. The corneal changes
      were characterised by epithelial haze and superficial stromal vascularisation
      which extended from the limbus towards the visual axis. Five patients were
      observed for a minimum of 18 months after stopping contact lens wear before
      undergoing limbal transplantation. A good result was obtained in 1 patient who
      had worn a contact lens in one eye only. Recurrent epithelial changes were
      observed on the recipient eyes of the remaining patients who had previously worn
      contact lenses bilaterally, and in 1 patient epithelial haze also developed
      adjacent to the donor site in the previously clinically normal donor eye. All 5
      patients experienced an improvement in symptoms post-operatively but in 2
      patients the visual acuity later deteriorated because of epithelial irregularity.
      The sixth patient has not had surgery. We conclude that limbal stem cell
      dysfunction in chronic contact-lens-associated epitheliopathy may be subclinical
      and that autograft transplantation in bilaterally exposed patients may fail to
      restore the epithelial phenotype of the host eye whilst jeopardising the
      epithelial integrity of the donor eye by depleting its stem cell reserve.

PMID- 8287984
TI  - Conjunctival autografting in the surgical management of pterygium.
AB  - In a retrospective survey of 117 operations for primary or recurrent pterygium,
      conjunctival autografting was compared with both excision without conjunctival
      closure ('bare sclera excision') and excision with complete conjunctival closure.
      The probability of corneal recurrence at 36 months after surgery was determined
      by survival curve analysis. In previously unoperated cases conjunctival
      autografting (n = 15) resulted in a 14% probability of recurrence, compared with
      70% for bare sclera excision (n = 50) and 69% for excision with complete
      conjunctival closure (n = 20). In previously operated cases conjunctival
      autografting (n = 17) resulted in a 7% probability of recurrence, compared with
      82% for bare sclera excision (n = 15). Hazard ratio analysis confirmed the
      statistical significance of these results at the 95% confidence level.
      Conjunctival autografting was more likely to produce an improvement in visual
      acuity than other forms of surgery.

PMID- 8287985
TI  - Orbital colour Doppler imaging.
AB  - Colour Doppler imaging (CDI) is an ultrasonic method for qualitatively and
      quantitatively assessing blood flow. Recently this technique has been adapted for
      investigation of the orbital, optic nerve and ocular vasculature. We discuss the
      history, principles and methodology of this examination technique for
      ophthalmology. Also described are normal haemodynamic characteristics as well as
      the findings in common pathological states involving derangements of orbital
      blood flow. Although CDI is relatively new to ophthalmology it has already proved
      to be of benefit in conditions with altered orbital, ocular and optic nerve blood
      flow. In the future it is expected that the indications for the applications of
      CDI will become more clearly defined and that orbital CDI will be more widely
      available and utilised, especially in the investigation of vascular diseases of
      the orbit, optic nerve and retina.

PMID- 8287986
TI  - Conjunctival involvement in malignancy-associated acanthosis nigricans.
AB  - Acanthosis nigricans classically presents with pigmented skin lesions over the
      neck, groin and axillae. It may involve the mucosal surfaces, particularly the
      oral mucosa. Conjunctival involvement is very rare, especially in the variety
      associated with malignancy. We report a case of acanthosis nigricans associated
      with squamous cell carcinoma of the bronchus where bilateral papillary
      conjunctivitis, progressing to hypertrophic papillary conjunctival and lid margin
      lesions, was the presenting feature. Topical treatment with corticosteroid and
      artificial tear drops resulted in the partial improvement of the ocular symptoms.

PMID- 8287987
TI  - Mitomycin-C concentration in human aqueous humour following trabeculectomy.
AB  - The aim of the study was to determine mitomycin-C (MMC) concentrations in human
      aqueous humour during trabeculectomy and to correlate anterior chamber
      concentrations with method of application. MMC was applied intra-operatively by
      saturating sponges, ranging in size from 2 x 2 x 5 mm to 2 x 4 x 10 mm on dry
      cut, with 0.5 mg/ml MMC during trabeculectomy for 3-5 minutes. Applications to
      episclera were made in 18 cases and to the scleral bed after scleral flap
      dissection in 9 cases. Aqueous samples were collected by paracentesis with a 30
      gauge needle 2-7 minutes after removal of sponge and external irrigation. Aqueous
      MMC concentrations were determined by high-performance liquid chromatography.
      Aqueous MMC concentration in 27 samples ranged from below minimum detectable
      concentration (less than 5 ng/ml) to 120.8 ng/ml. Mean aqueous drug levels
      obtained when the applications were to the scleral bed were 35.65 +/- 39.17 ng/ml
      (range 5-120.8 ng/ml). Applications on episclera gave mean aqueous concentrations
      of 4.98 +/- 9.11 ng/ml (range 0-33.3 ng/ml). The difference was statistically
      significant (p = 0.004). There were no correlations between sponge size, time of
      MMC exposure and aqueous MMC level. In conclusion, MMC is detectable in aqueous
      humour within minutes of external application and the aqueous concentration level
      is higher if the application is in the scleral bed than on the episclera.
      Toxicity of the drug at this concentration range for corneal endothelial cells
      needs further investigation via in vitro and clinical studies.

PMID- 8287988
TI  - Holmium laser sclerostomy: a clinical study.
AB  - A prospective study of 30 glaucoma patients (one eye in each patient) treated by
      an ab externo holmium laser sclerostomy is presented. An average of 40.2 pulses
      with an energy of 100 mJ was necessary to produce a filtering bleb. The average
      pre-operative intraocular pressure was 25.5 +/- 7.4 mmHg, with an average of
      14.06 +/- 5.7 mmHg post-operatively at the final follow-up. The mean follow-up
      was 7.5 months (range 5-12 months) and the mean age of the patients was 71.4
      years. Using strict criteria 70% of sclerostomies were considered successful at
      the final follow-up visit. The main post-operative complication was iris plugging
      of the sclerostomy. This was dealt with successfully with a 'Q'-switched
      neodymium:YAG laser in 80% of cases. Our early experience with the laser suggests
      that it is an easy, quick method of producing a filtering bleb, and may be
      carried out as an office procedure. As the technique evolves its long-term
      success remains to be evaluated; however, it shows promise both as an alternative
      to trabeculectomy as a primary procedure and as an additional technique for more
      complicated cases of glaucoma.

PMID- 8287989
TI  - Improved lung function tests on changing from topical timolol: non-selective beta
      blockade impairs lung function tests in elderly patients.
AB  - Fifty-two elderly glaucomatous patients, without a history of asthma or
      obstructive airways disease, who were using topical timolol for control of
      intraocular pressure were recruited. Their topical therapy was changed to either
      betaxolol or pilocarpine. The change was associated with improvement in mean peak
      flow from 278 l/min to 328 l/min (t = 5.73, p < 0.001), mean FEV1 from 1.66 l to
      1.85 l (t = 7.09, p < 0.001) and mean FVC from 2.40 l to 2.64 l (t = 5.07, p <
      0.001). Change to either betaxolol or pilocarpine was associated with improved
      lung function tests. Lung function tests in a control group of 20 showed no
      significant changes. Both drugs maintained control of intraocular pressure but
      betaxolol had fewer ocular side effects.

PMID- 8287990
TI  - Extensive visual loss with topical facial steroids.
AB  - Steroid creams applied topically to the skin are routinely used in the treatment
      of many dermatoses. Their use on the face in severe atopic eczema is relatively
      common. We report a series of three patients who whilst using topical facial
      steroids developed advanced glaucoma. A further two cases of ocular hypertension
      secondary to topical facial steroids are also described. This is the first series
      of cases to be reported demonstrating the potentially blinding complications of
      topical facial steroids. Recommendations are made with regard to screening such
      patients for glaucoma.

PMID- 8287991
TI  - The National Cataract Surgery Survey: III. Process features.
AB  - The process of how medical care is provided for cataract patients within the
      National Health Service is reported in this paper with particular emphasis on
      features relating to access to surgery and delivery of the surgical service.
      Access to the hospital eye service is considered in terms of lengths of waiting
      time and level of visual impairment at specific periods of patient care: first
      assessment in an ophthalmic out-patient clinic, at listing for surgery and for
      admission for surgery. Delivery of the surgical service is considered in terms of
      threshold of visual acuity at which surgery is considered necessary and some
      features of post-operative management: length of stay, duration of post-operative
      medication, number of post-operative out-patients visits and whether final
      refraction had been performed and spectacles dispensed by 3 months after surgery.
      Regional operation rates are presented as indicators of activity. These results
      describe the experience of a sample of all patients admitted for cataract surgery
      in 1990 and provide national figures for the process features considered in this
      report with respect to current surgical practice in the United Kingdom.

PMID- 8287992
TI  - Is cortical spoke cataract due to lens fibre breaks? The relationship between
      fibre folds, fibre breaks, waterclefts and spoke cataract.
AB  - Fibre folds, previously called lamellar separation of the lens, have been found
      by electron microscopy to be associated with fibre breaks, which are seen in vivo
      as the circular shades of Obazawa. This led to the present study to determine the
      relationship between fibre folds, fibre breaks, waterclefts and spoke cataract.
      All lenses with fibre folds were found to have circular shades. A few instances
      of circular shades without fibre folds were found, suggesting that the fibre
      break may be the primary pathology. It was found that circular shades occurred in
      association with spoke cataract only when fibre folds were also present. Thus
      there is no essential causal relationship between fibre breaks and spoke
      cataract. The occurrence of waterclefts was unrelated to the presence of the
      other features. The lower nasal quadrant of the lens was the most common site for
      the four features. The depth of spoke cataracts was found to be unrelated to the
      age of the patient, which makes it unlikely that accommodational stress at the
      time of onset of presbyopia is causative.

PMID- 8287993
TI  - Can second eye cataract extraction be justified?
AB  - A prospective study was carried out to test the null hypothesis that there is no
      additional benefit to be gained from second eye cataract extraction. Twenty-nine
      patients with unilateral cataract but contralateral pseudophakia completed a
      questionnaire enquiring into their visual disability and underwent testing of
      monocular and binocular visual acuity, contrast sensitivity, glare disability,
      fusion and stereopsis. These tests were repeated 4 months after second eye
      cataract extraction and lens implantation. Patients universally considered their
      vision to have been improved by second eye surgery and the prevalence of all
      symptoms were significantly reduced by this procedure. Normal binocular summation
      and stereopsis were restored following second eye cataract extraction.
      Symptomatic patients may benefit from second eye cataract extraction with lens
      implantation.

PMID- 8287994
TI  - The treatment of epiphora with balloon dacryocystoplasty.
AB  - We examine a new treatment for epiphora: balloon dilatation of the nasolacrimal
      duct, or dacryocystoplasty. The procedure, which was performed as an out-patient
      procedure under local anaesthetic, was carried out on 20 patients with epiphora,
      17 due to anatomical and 3 due to functional obstruction. There was an overall
      success rate of 60%, with complete relief of symptoms in 4 patients and a
      symptomatic improvement in another 8 (follow-up 2-9 months, mean 4.2 months). All
      patients tolerated the procedure well with minimal per-operative and post
      operative discomfort. A higher success rate was seen in those patients with
      either a low anatomical or a functional obstruction. The procedure can be easily
      repeated and, if unsuccessful, still allows a dacryocystorhinostomy to be
      performed at a later date.

PMID- 8287995
TI  - Cine magnetic resonance imaging of eye movements.
AB  - Cine magnetic resonance imaging (MRI) is a technique in which multiple sequential
      static orbital MRI films are taken while the patient fixates a series of targets
      across the visual field. These are then sequenced to give a graphic animation to
      the eyes. The excellent soft tissue differentiation of MRI, combined with the
      dynamic imaging, allows rapid visualisation, and functional assessment of the
      extraocular muscles. Good assessment of contractility can be obtained, but the
      technique does not allow study of saccadic or pursuit eye movements. We have used
      this technique in 36 patients with a range of ocular motility disorders,
      including thyroid-related ophthalmopathy, blow-out fracture, post-operative lost
      or slipped muscle, and Duane's syndrome.

PMID- 8287996
TI  - Day case management in adjustable suture squint surgery.
AB  - Day case adjustable suture squint surgery is limited by patient cooperation in
      the early post-operative period. Nausea is common and may be exacerbated by
      adjustment. To facilitate early adjustment, in 37 consecutive patients
      anaesthesia was induced with propofol and the airway maintained with a laryngeal
      mask. Before and after adjustment patients recorded their level of nausea on a
      visual analogue scale (1 = no nausea, 10 = vomiting). The mean age of the group
      was 31.9 years with 20 men and 17 women. Adjustment was performed at a mean time
      of 4.9 hours after surgery. On the analogue scale of nausea the mean score was
      1.54 pre-adjustment and 1.73 post-adjustment. Only 1 patient was given a post
      operative anti-emetic. All patients were sufficiently alert to adjust without
      difficulty and were discharged the same day. The use of a laryngeal mask and
      induction of anaesthesia with propofol in adjustable suture squint surgery
      facilitates early adjustment and thus day case management.

PMID- 8287997
TI  - The effect of acetazolamide on the retinal circulation.
AB  - The effect of the carbonic anhydrase inhibitor, acetazolamide, on the retinal
      circulation was studied in 10 healthy volunteers. Acetazolamide was administered
      intravenously at a dose of 500 mg. Retinal blood flow was determined from red
      cell velocity using laser Doppler velocimetry and vessel diameter measurement
      using computerised digital image analysis of monochromatic fundus photographs.
      There was a significant increase in retinal blood flow at 30 minutes and 60
      minutes after acetazolamide injection (p = 0.002). Retinal vessels showed
      vasodilatation reaching significant levels 60 minutes after the injection (p <
      0.03). An increase in red cell velocity was observed at 30 and 60 minutes (p <
      0.002). A significant reduction in intraocular pressure occurred at 30 and 60
      minutes after the injection (p < 0.001). The mechanisms responsible for the
      increase in retinal blood flow acted via significant increases in perfusion
      pressure (p < 0.05), red cell velocity (p < 0.002) and retinal vessel dilatation
      (p < 0.03). An increase in tissue PCO2 and a reduction in pH are thought to be
      responsible for the vascular dilatation. The increase in retinal blood flow with
      acetazolamide may serve to limit optic disc and retinal ischaemia in acute
      glaucoma and central retinal artery occlusion respectively.

PMID- 8287998
TI  - Laser photocoagulation for proliferative retinopathy in sickle haemoglobin C
      disease.
AB  - The effect of sectoral, scatter laser photocoagulation on proliferative sickle
      retinopathy (PSR) was investigated by reviewing fluorescein angiograms of 88
      sickle cell-haemoglobin C patients enrolled in a controlled, randomised trial.
      Follow-up was for a median period of 2.9 years. Complete infarction of all PSR in
      an eye occurred in 7 of 74 treated eyes and 2 of 60 control eyes. Treatment
      resulted in significantly greater regression (decrease in number or size of PSR
      lesions) in eyes of patients aged < 25 years at enrollment but not in eyes of
      patients > or = 25 years at enrollment. Infarction of individual PSR lesions was
      significantly more common in treated eyes. Treated PSR was significantly more
      likely to infarct if small (< 15 degrees circumferential involvement) and if flat
      rather than elevated. New PSR was significantly less likely to develop in treated
      eyes.

PMID- 8287999
TI  - Specular microscopy of the anterior intraocular lens surface.
AB  - Until recently the cytological assessment of the intraocular lens (IOL) surface
      was only possible using in vitro cytopathological techniques on explanted lenses
      or in animal models. Specular microscopy provides an in vivo method for the
      observation of the IOL surface at high magnification. We have used this technique
      to examine the IOL surface of 27 normal pseudophakic eyes in the first 3 months
      following implantation. Cellular deposits consisting of small and giant
      inflammatory cells were found to be a normal occurrence in otherwise clinically
      successful cataract surgery. It was also possible to visualise the anterior
      capsule and its attachment to the IOL surface, an amorphous surface membrane,
      pigment, surface contaminants (starch granules and fibres), and the markings
      caused by instrumentation at the time of implantation. The technique of IOL
      surface specular microscopy therefore provides a useful method for the
      visualisation of the IOL surface and the cytological reaction that occurs there,
      and thus allows an assessment of IOL biocompatibility.

PMID- 8288000
TI  - Choroidal melanoma presenting as vitreous haemorrhage.
AB  - Vitreous haemorrhage is an unusual presenting feature of malignant melanoma of
      the choroid. We describe three cases in which this occurred. The three tumours
      shared a number of common features: all were located in the peripheral choroid,
      were of a similar size and had a small herniation of tumour tissue through
      Bruch's membrane. We believe that vascular congestion caused by constriction of
      the tumour vasculature at the site of herniation is the most probable cause for
      the haemorrhage in these cases. We review the relevant literature and discuss
      some of the commoner differential diagnoses.

PMID- 8288001
TI  - Serious eye injuries caused by coin throwing.

PMID- 8288002
TI  - Unexplained foreign body sensation: Thinking of loiasis in at risk patients
      prevents significant morbidity.

PMID- 8288003
TI  - Cotton-wool spots in giant cell arteritis.

PMID- 8288004
TI  - Ophthalmic Munchausen's syndrome.

PMID- 8288005
TI  - European Community controls for high temperature testing of food contact
      materials.
AB  - High temperature testing above 121 degrees C is currently in accordance with
      national legislation, although amended Council Directive 82/711/EEC will include
      a framework of temperatures and times, the most stringent of which will require 2
      h testing of materials and articles at 175 degrees C with olive oil. The
      background debate that preceded the establishment of this proposed framework is
      described, as well as the difficulties that were encountered over agreeing the
      appropriate testing for microwave susceptors. The further work that will be
      required for implementation (and will need to be undertaken by groups such as
      CEN) is outlined as are areas such as testing above 175 degrees C that may
      require consideration for future EC control.

PMID- 8288006
TI  - Use of high temperature-resistant sorbents as simulants for testing.
AB  - The amended Council Directive 82/711/EEC will include the test conditions for
      plastic materials and articles intended to come into contact with foodstuffs at
      high temperature. The most stringent test condition (excluding susceptor
      materials) will be heating of the material for 2 h at 175 degrees C in a
      conventional oven. For fatty foodstuffs, olive oil (simulant D), synthetic
      triglycerides or sunflower oil shall be used for the test. If these simulants are
      found inappropriate, other simulants and conditions of time and temperature may
      be used. In order to perform a correct evaluation of such materials one must
      distinguish between volatile and non-volatile migrants, between additives and
      decomposition products, and between overall and specific migration. No
      universally applicable simulant has been found yet which is able to provide all
      the data needed for evaluation. The advantages and limitations of a high
      temperature-resistant simulant will be described.

PMID- 8288007
TI  - Migration testing with olive oil in a microwave oven.
AB  - A study was carried out to compare the overall migration from packaging materials
      into olive oil during heating in a microwave oven, and the overall migration from
      the same materials into olive oil but applying time and temperature conditions
      stipulated in the current EC and Dutch legislation on food packaging. Application
      of additional test conditions (e.g. 30 min and 1 h in combination with test
      temperatures exceeding 121 degrees C, and a test temperature of 130 degrees C)
      have demonstrated the need for extension of the test conditions mentioned in
      existing food packaging regulations to enable realistic migration testing of
      microwave packaging materials under conventional test conditions. It is concluded
      that the overall migration into olive oil from packaging materials intended for
      microwave oven use, including susceptor materials, can be judged on the basis of
      migration testing using conventional heating. For testing film or susceptor
      materials in a microwave oven by one-sided contact, a migration cell transparent
      to microwaves was developed and used up to 200 degrees C. In conventional high
      temperature tests applying hot-filling of trays or migration cells, a temperature
      drop was observed, while handling oil at temperatures of 150 degrees-175 degrees
      C may be considered perilous. To prevent problems of this kind it is proposed to
      start migration tests at room temperature and to heat the simulant rapidly to the
      final test temperature. This procedure is comparable to migration tests carried
      out with aqueous food simulants at 121 degrees C in an autoclave.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8288008
TI  - Combined compositional analysis and threshold of regulation as a possible control
      measure for microwave susceptors.
AB  - A testing scheme is described whereby the susceptor is heated in an enclosed
      system and potential volatile migrants detected by GC-FID or GC-MS. This
      compositional information is then combined with knowledge on the relationship
      between volatility and transfer to foods to predict migration levels. The scheme
      can be simplified to a threshold of regulation approach by addition of internal
      standards at suitable concentrations. This approach could be of value in
      screening new susceptor compositions for potential migrants, followed, as
      required, by more exhaustive testing using foods or food simulants. In support of
      this approach, 15 model substances with a boiling range of 77-440 degrees C were
      incorporated into susceptors via the vapour phase or by formulation into the
      adhesive. Migration to microwaved foods was measured to provide the required
      information on the approximate relationship between the boiling point of a
      potential migrant and its migration level. The impregnated susceptors were also
      used to measure migration of the model substances to the test simulants Tenax and
      a semi-solid simulant of olive oil and water absorbed on an inert support.
      Migration to both simulants was much higher than to foods, indicating that for
      volatiles analysis at least, both simulants are suitable for screening purposes
      and err on the side of safety.

PMID- 8288009
TI  - Safety assessment of microwave susceptors and other high temperature packaging
      materials.
AB  - A number of packaging materials are being used not only to contain food during
      distribution but also to serve as the cooking container. The higher temperatures
      that these materials reach led the US Food and Drug Administration (FDA) to issue
      an intent to publish new regulations in 1989. The food and packaging industries
      responded by conducting extensive research and submitting the results to FDA. The
      methods used and results obtained are discussed. Most of the data were focused on
      microwave susceptors and the volatile compounds generated. One project showed
      that for a specific product, popcorn, there was no transfer into the food. Work
      is continuing to validate methods to test for non-volatile compounds. In addition
      to susceptors, various paper and plastic materials are used in dual ovenable
      (microwave and conventional ovens) applications. Most of the research on these
      materials has investigated the food contact temperatures on testing for migrants.
      An update on the current regulatory status of packaging materials intended for
      high temperature use in the US is discussed.

PMID- 8288010
TI  - Temperature measurement during microwave cooking.
AB  - Product development of microwavable foods originally suffered from a high degree
      of non-uniform heating which is generic in microwave heating. Typically, foods
      have suffered from either overheated edges or under heated centres. This was
      compounded by short reheat times which allowed little opportunity for temperature
      equilibration. A crucial step in overcoming this problem has been the
      understanding provided from time-temperature data. Conventional temperature
      measurements by thermocouple, etc. are inappropriate in microwave cooking due to
      the high electric fields which are present (ca 15 kV/m). The result is either
      very significant interference, or even failure of the sensor. Therefore,
      alternative methods were developed to meet the need, some of which are discussed
      in this paper. One such measurement system is the now commonplace fibre optic
      probe, originally from Luxtron. The discrete data provided from this system are
      compared with the surface imaging data delivered by thermal imaging. These
      techniques are discussed in the context of microwave packaging materials heated
      in situ in a microwave oven and the need for temperature data as a basis for
      establishing testing regimes.

PMID- 8288011
TI  - Ovarian cancer and assisted reproductive technology.

PMID- 8288012
TI  - Management of severe, early pre-eclampsia: is conservative management justified?
AB  - A retrospective analysis was performed to assess the fetal and maternal benefits
      of allowing women presenting with severe pre-eclampsia between 24 and 32 weeks to
      continue their pregnancy following treatment of their hypertension. Cases
      presenting in Oxford (conservative management) and in Birmingham (stabilisation
      and early intervention) were compared. Patients were considered to require
      treatment when their systolic blood pressure was > or = 170 mmHg systolic or > or
      = 110 mmHg diastolic, associated with at least 1+ proteinuria and hyperuricaemia.
      We compared gestation at delivery, birth weight and neonatal complications for
      each group, and any maternal morbidity. There were 28 patients in each group.
      Gestational age at delivery was significantly less in the group managed by early
      intervention. Those women managed conservatively gained a mean of 9.5 days (range
      2-26 days; P < 0.05), and their birthweight was significantly greater (P < 0.05).
      There was a significant difference between the length of stay in the neonatal
      intensive care unit between the 2 groups (P < 0.05), the babies of those women
      managed conservatively staying a mean of 7.4 days less. There were fewer neonatal
      complications in those cases managed conservatively, the number of newborns with
      1 or more complications in the early intervention group being 18 (64.3%),
      compared with 8 (28.6%) in the expectant management group (P = 0.0001). All of
      the women in the group managed by early intervention recovered with no severe
      complications. However, those women managed conservatively had a higher incidence
      of HELLP (2 cases) and ELLP syndrome (2 cases), 1 case requiring temporary renal
      dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288013
TI  - Post caesarean section delivery.
AB  - Recent clinical attention has focused upon the rising rate of caesarean sections
      being performed and whether patients with a previous caesarean section should be
      allowed a vaginal delivery. In this paper, the worldwide trend of caesarean
      section and the role of trial of scar following single and multiple caesarean
      surgery is reviewed. The role of oxytocin and regional epidural analgesia is
      evaluated as well as perinatal and maternal mortality. On the basis of the
      available data, there is no justification for the current clinical practice of
      almost 99% prevalence of elective repeat caesarean section in some hospitals in
      the North America. Oxytocin and epidural analgesia, when carefully monitored, are
      safe and reasonable in these patients. Watchful waiting has always been an
      essential virtue in obstetric management and should not be replaced by hopeful
      expectancy. This aspect of the art of obstetrics would appear to require
      rejuvenation if we are to stem the rising tide of caesarean sections.

PMID- 8288014
TI  - Immunohistologic demonstration of endothelial disruption in acute atherosis in
      pre-eclampsia.
AB  - Acute atherosis is a vasculopathy described in maternal vessels in the uterus in
      pre-eclamptic pregnancies. We wished to document whether, and to what extent,
      endothelial disruption was present in acute atherosis. Using a standard
      streptavidin-biotin-peroxidase immunohistologic method, we found extensive
      endothelial disruption in 5 cases of acute atherosis. In 2 cases, there was
      aneurysmal formation associated with the acute atherosis and endothelial
      disruption in these 2 cases was focal and less extensive. All acute atherosis
      lesions were related to thrombosis. None of the women had taken aspirin. We
      suggest that studies on the maternal uteroplacental vasculature in women who have
      had aspirin during pregnancy should be performed.

PMID- 8288015
TI  - Vaginal uterine amputation.
AB  - Since sexual dysfunction after hysterectomy might be prevented by leaving the
      portio in place, a technique was developed to perform vaginal uterine amputation.
      The method appeared to have been described already 40 years ago but has vanished
      from textbooks since then.

PMID- 8288016
TI  - Women's opinion on withdrawal bleeding with hormone replacement therapy.
AB  - The objective of the study was to assess the opinion of women about the use of
      hormone replacement therapy (HRT) in relation to continuation or re-induction of
      bleeding periods after menopause. The design was a population-based cross
      sectional study using a postnatal questionnaire in Krimpen aan den IJssel, a
      commuter suburb of Rotterdam. The participants were all 2729 women living in
      Krimpen aan den IJssel aged 45-60 years, of whom 1947 (71.3%) responded. The main
      outcome measure was an opinion on monthly or trimonthly withdrawal bleedings with
      HRT. The results showed 16.9% of all women have no or little objection to use of
      HRT with monthly withdrawal bleedings. There is a marked difference between
      premenopausal women (32.4% have no or little objection) and postmenopausal women
      (only 9.2% have no or little objection). Trimonthly cycles during HRT tend to be
      perceived as more acceptable (41.4% of premenopausal women and 11.8% of
      postmenopausal women have no or little objection). It is concluded that a
      reasonable proportion of premenopausal women accept continuation of periodic
      bleeding with HRT. There is a preference for trimonthly cycles rather than
      monthly withdrawal bleedings. Most postmenopausal women object to having
      withdrawal bleedings with HRT, irrespective of a monthly or trimonthly cycle.
      Research should continue on schedules without withdrawal bleedings.

PMID- 8288017
TI  - Energy economy in the pregnant human uterus at term: studies on arteriovenous
      differences in metabolites of carbohydrate, fat and nucleotides.
AB  - Metabolic regulation was studied in the pregnant human uterus by determining its
      uptake and release of various substrates, some of which are commonly used as a
      fuel and some are markers of disturbed energy status in cells. Ten healthy women
      with normal pregnancy were examined when undergoing elective Caesarean section at
      term, before onset of labour. Carbohydrate metabolites (glucose, lactate and
      pyruvate), fat metabolites (free fatty acids (FFA) and glycerol) and nucleotide
      metabolites (hypoxanthine, xanthine and urate) were determined in arterial
      (radial artery) and venous (plexus of the uterine and ovarian veins) blood. In
      addition the arteriovenous difference in each substance across the uterus was
      calculated. A distinct uptake of glucose was a typical finding in the pregnant
      uterus as reflected by a positive difference. On the other hand, glycerol and FFA
      were released from the pregnant uterus. Similarly, a degradation of adenine
      containing nucleotides seemed to be continuously ongoing in the pregnant uterus,
      since oxypurines displayed a negative difference as well.

PMID- 8288018
TI  - Localization of alpha 2, alpha 5 and alpha 6 integrin subunits in human
      endometrium, decidua and trophoblast.
AB  - Integrins are heterodimeric glycoproteins acting as membrane receptors for
      extracellular matrix components. The specificity of these receptors towards one
      particular matrix glycoprotein depends on the type of alpha and beta subunit
      combination. Since integrins are involved in the migratory behaviour of cells and
      since cytotrophoblastic cells are constitutively invasive, we undertook to
      immunolocalize the alpha 2, alpha 5 and alpha 6 integrin subunits in normal and
      hydatidiform molar trophoblast, in an implantation site as well as in
      decidualized and non-decidualized endometrium. alpha 6 positivity was confined to
      villous cytotrophoblast and was clearly polarized towards the basement membrane.
      Extravillous cytotrophoblastic cells were alpha 6-negative but became alpha 5
      positive. In contrast to normal trophoblast, villous cytotrophoblast from
      hydatidiform molar tissue was alpha 5-positive. We conclude that the expression
      of a alpha 5 integrin subunit on cytotrophoblastic cell surfaces is correlated
      with the appearance of an invasive phenotype. alpha 6 and alpha 2 integrin
      subunits were both localized on the surface and glandular epithelium of the
      endometrium and their expression was increased during the secretory phase but
      became low or undetectable after decidualization. In contrast, alpha 5 subunit
      positivity was weak in the same epithelial during the first half of the cycle but
      disappeared after ovulation. Stromal cell alpha 5 positivity was present
      throughout the cycle but increased dramatically in decidualized endometria. We
      conclude that the alpha 5 integrin subunit which disappears from the epithelium
      at the end of the cycle might allow migration of the epithelial cells and repair
      of the endometrium after menses. We also wonder if alpha 5 positivity is part of
      a change in the stromal cell phenotype induced by decidualization.

PMID- 8288019
TI  - Polysialic acids.
AB  - 1. Polysialic acids are linear homopolymers of N-acetylneuraminic acid (Neu5Ac),
      N-glycolylneuraminic acid (Neu5Gc) and deaminated neuraminic acid (KDN) residues
      joined by alpha 2,8, alpha 2-9 or alpha 2,8/alpha 2,9 ketosidic linkages. 2. They
      occur in glycoproteins of embryonic neural membranes (playing a role of neural
      cell adhesion molecules), in non-neural tissues (postnatal kidney), tumours,
      (neuroectodermal tumours), fish eggs and in the capsule of certain bacteria such
      as Neisseria meningitidis group B. 3. These polymers are synthesized through
      reactions which involve (a) the synthesis of sialic acid; (b) its activation to a
      cytidine monophosphate sugar nucleotide and (c) the polymerization of the
      different residues by a polysialyl-transferase complex. 4. Polysialic acids are
      involved in organogenesis and in cell growth. In several tissues they act as
      oncodevelopmental antigens, and in bacteria are also virulent determinants.

PMID- 8288020
TI  - Homopurine/homopyrimidine sequences as potential regulatory elements in
      eukaryotic cells.
AB  - 1. Homopurine/homopyrimidine (PuPy) repetitive duplex sequences can form
      intramolecular triplexes (H-DNA) or intermolecular triplexes with a third strand
      in a sequence-specific manner. 2. Such sequences are present in natural genomes
      within 5'- and 3'-flanking sequences and coding regions of genes. Triplex DNA
      structures have been detected in vitro and in vivo and have been immunolocalized
      to chromosomes by triplex-specific monoclonal antibody approaches. 3.
      Intermolecular triplex formation represses gene expression at the transcriptional
      level and is also useful in genomic mapping, gene cloning, sequence-specific drug
      delivery, and selective modulation of gene expression.

PMID- 8288021
TI  - Effect of a high fat diet on phospholipid class distribution and fatty acid
      composition in rat liver.
AB  - 1. Long term consumption (20 weeks) of a high fat diet (65% of the energy content
      as fat) rich in either saturated [30% (w/w) coconut oil] or unsaturated [30%
      (w/w) sunflower oil] fatty acids resulted in strikingly similar alterations in
      the phospholipid class distribution and fatty acid composition in the liver of
      male Wistar rats. 2. The effect of these two diets was compared to a control
      group maintained on a 2% fat diet (w/w) for the same time interval. 3. In spite
      of the difference in the PUFA/SFA (polyunsaturated fatty acid/saturated fatty
      acid) ratio between the two high fat diets (0.1, saturated fatty acid diet; 5.4,
      unsaturated fatty acid diet), both diets resulted in a similar PUFA/SFA ratio in
      liver phospholipids, a similar reduction in palmitic acid (16:0), oleic acid
      (18:1, n-9) and arachidonic acid (20:4, n-6) and an elevation in stearic acid
      (18:0), linoleic acid (18:2, n-6) and docosahexaenoic acid (22:6, n-3). 4.
      Further, changes in the phospholipid classes were also similarly affected by both
      high fat diets.

PMID- 8288022
TI  - The mechanism of interaction of ceruloplasmin with superoxide radicals.
AB  - 1. The mechanism of interaction of CP with O2- radicals in chemical and enzymatic
      systems of superoxide radical generation as well as in the pulse radiolysis
      technique was studied. 2. It is found that CP does not exert any kinetic
      influence on the decomposition of superoxide radical and, unlike SOD, cannot
      catalyze the reaction of disproportionation of these radicals in systems with
      chemical and enzymatic generation of O2-. 3. The data obtained confirm the
      suggestion that CP interacts with precursors of O2- radicals. 4. The irradiation
      of CP does not change its inhibiting activity in the reaction of the formation of
      superoxide radicals in systems with enzymatic O2- generation, but decreases its
      oxidase activity. 5. The results obtained demonstrated that the increase in the
      radiation dose resulted in the decrease of the inhibiting activity of SOD,
      whereas the activity of CP did not change.

PMID- 8288023
TI  - The self-association of ovine erythrocyte spectrin.
AB  - 1. Spectrin extracted from ovine erythrocyte membranes at low temperature shows
      association behaviour similar to that reported for human and bovine erythrocytes.
      2. The spectrin tetramer is the predominant oligomer, the dimer is well
      represented, and smaller amounts of hexamer and higher oligomers are present. 3.
      The estimates of parameters describing the self-association of purified ovine
      spectrin studied by sedimentation equilibrium analysis were found to be
      indistinguishable from those obtained for human spectrin under the same
      conditions, within the precision of the measurements. 4. The data suggest that
      the cooperative isodesmic model may be general for spectrin, and not a
      peculiarity of the human.

PMID- 8288024
TI  - The effect of D2O on glycolysis by rat hepatocytes.
AB  - 1. The effect of incorporating D2O into the incubation medium on glycolysis and
      gluconeogenesis by hepatocytes from fasted rats was examined. 2. The substitution
      by heavy water, D2O, at concentrations from 10 to 40%, stimulated glucose uptake,
      lactate production and CO2 yields from glucose. At 10 mM glucose, 40% D2O doubled
      glucose uptake, increased CO2 production by 40%, and increased lactate production
      by 350%. 3. The stimulation of lactate production decreased at higher glucose
      concentrations, but was still substantial even at 80 mM glucose. 4. There was no
      effect on CO2 production above glucose concentrations of 30 mM. 5. Ten percent
      D2O showed little inhibition of lactate uptake, its oxidation and
      gluconeogenesis. At 40% D2O the inhibition ranged from 10 to 20%. 6. No effect of
      D2O on the rate of glucokinase or glucose-6-phosphatase was observed. 7. The
      concentration of fructose, 2,6-P was not affected by D2O.

PMID- 8288025
TI  - S-D-lactoylglutathione accumulation in activated human platelets.
AB  - 1. S-D-Lactoylglutathione accumulates in human platelets activated by agonists.
      Among the tested inducers thrombin is the most active. 2. The effect is dose and
      time-dependent. S-D-Lactoylglutathione, corresponding to depleted pool of reduced
      glutathione, can also be detected in platelets incubated with exogenous
      methylglyoxal. 3. A further significant increase was observed in platelets
      stimulated with thrombin in the presence of methylglyoxal. 4. No change in
      glyoxalase activities upon platelet stimulation with thrombin was shown.

PMID- 8288026
TI  - Comparison of metabolic effects of EGF, TGF-alpha, and TGF-beta 1 in primary
      culture of fetal bovine myoblasts and rat L6 myoblasts.
AB  - 1. Comparative studies of EGF, TGF-alpha, and TGF-beta 1 action on the synthesis
      of DNA and cellular proteins in rat L6 myogenic cells and fetal bovine myoblasts
      demonstrated considerable differences between particular growth factors,
      dependent on dose and target cells. 2. Among examined growth factors only EGF
      exerted mitostimulatory action, more pronounced at lower concentrations. EGF,
      progressively with dose, stimulated protein synthesis much more effectively in
      fetal bovine myoblasts than in L6 cells. 3. The dynamics of stimulation of
      protein synthesis by TGF-alpha was greater than by EGF in both examined types of
      cell cultures. 4. The maximal response of fetal bovine myoblasts to TGF-alpha in
      a concentration of 100 ng/ml reached 370%, whereas EGF in a 10 times higher
      concentration stimulated protein synthesis only to 123% of control. 5. In
      contrast to EGF, TGF-alpha significantly inhibits DNA synthesis. Inhibition of
      the mitogenic response with simultaneous stimulation of protein synthesis by TGF
      alpha may indicate changes toward cell differentiation. 6. TGF-beta 1 in smallest
      concentration inhibits both DNA and protein synthesis. The suppressive action of
      TGF-beta 1 was more distinct in fetal bovine myoblasts than in the L6 cell line.
      7. Increasing concentrations of TGF-beta 1 diminished its inhibitory effect, even
      leading to stimulation of protein synthesis at higher doses in L6 myoblasts.

PMID- 8288027
TI  - 1H NMR study of metabolic alterations in the small intestine of rats infected
      with Hymenolepis diminuta.
AB  - 1H NMR spectra of the duodenum, jejunum and ileum tissues of the small intestine
      of a rat showed metabolic gradients. 2. The concentrations of metabolites in
      these gut regions were altered by the presence of the tapeworm Hymenolepis
      diminuta. 3. In the infected duodenum there was significantly less glycogen,
      glucose and phosphocreatine/creatine, but significantly more lactate than in the
      corresponding controls. 4. Infected jejunum contained significantly less betaine
      but significantly more succinate, alanine and lactate. 5. Infected ileum had
      significantly less glycogen and taurine but significantly more alanine and
      lactate.

PMID- 8288028
TI  - Localization of the glucocorticoid receptor in rat liver cells: evidence for
      plasma membrane bound receptor.
AB  - 1. The cytoplasmic glucocorticoid receptor of rat liver cells is in part
      recovered in the plasma membrane fraction. 2. After in vivo administration of
      [3H]dexamethasone, 0.35% of the radioactivity recovered is bound on plasma
      membranes. 3. Dexamethasone also binds in vitro specifically to plasma membranes.
      Expressed as fmol/mg protein, binding of dexamethasone to plasma membranes is
      comparable to binding to the soluble cytoplasmic fraction (cytosol). 4. Using
      polyclonal antibody to the glucocorticoid receptor and the indirect
      immunofluorescence technic, an intense decoration of the plasma membranes is
      observed, denoting a high concentration of glucocorticoid receptor on plasma
      membranes. 5. The localization of the receptor on plasma membranes could be of
      potential importance for its interaction with agents (mitogens, growth factors)
      initially acting on the cell membrane, regulating subsequent cell proliferation
      and growth at the level of the cell nucleus.

PMID- 8288029
TI  - Effect of dehydroepiandrosterone on pentose phosphate pathway activity in the rat
      colon.
AB  - 1. The effects of fasting and fasting followed by refeeding on the activities of
      the oxidative pentose pathway (OPP) and the non-oxidative pentose pathway (NOPP)
      were estimated by the rate of production of 14CO2 from [1-14C] glucose in
      isolated rat colonocytes, and the production of hexose 6-phosphates from ribose 5
      phosphate in rat colonic cytosols, respectively. 2. The OPP activity in
      colonocytes from rats in the fasted state was 50% lower when compared to
      colonocytes from rats refed after a fast. This indicated induction of the rate
      limiting enzyme of the OPP, glucose 6-P dehydrogenase (G6-PDH) in the latter
      instance. No effect on the maximal catalytic activity of the enzymes of the NOPP
      was seen in colonocytes from rats refed after a fast compared with colonocytes
      from rats in the fasted state. 3. Isolated colonocytes obtained from the distal
      colon of rats refed after a fast, showed a significant decrease (30%) in OPP
      activity when incubated with 50 microM dehydroepiandrosterone (DHEA). A similar
      degree of inhibition was seen with 10 mM butyrate (P < 0.05). In contrast, using
      colonic cytosols, both DHEA and butyrate had no effect on the maximal catalytic
      activity of the NOPP. 4. Intraperitoneal injection (i.p.) of DHEA in rats refed
      after a fast showed a significant increase in the maximal catalytic activity of
      the NOPP in the distal colon (46%; P < 0.05). A similar elevation in the maximal
      catalytic activity of the NOPP was seen in the distal colon of DHEA treated pair
      fed rats (43%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288030
TI  - Changes in myosin heavy chain isoform expression of overloaded rat skeletal
      muscles.
AB  - 1. The effect of functional overload produced by tenotomy of synergistic
      gastrocnemius muscle on the expression of myosin heavy chain (MHC) isoforms in
      the plantaris and soleus muscles of the rat was studied using gradient sodium
      dodecyl sulfate-acrylamide gel electrophoresis. 2. Five weeks tenotomy, the
      plantaris and soleus muscle weights induced by tenotomy of the gastrocnemius
      muscle were 44.3% (P < 0.005) and 37.4% (P < 0.005), respectively, heavier than
      the contralateral control muscles. 3. Although four types of MHC isoforms were
      observed in both control and experimental plantaris, the percentage of MHC
      isoforms in the control and experimental muscles differed; the hypertrophied
      plantaris muscle contained more HCI (P < 0.05), HCIIa and HCIId (P < 0.05) and
      less HCIIb (P < 0.05) than the control muscle. 4. The control soleus muscle
      contained two MHC isoforms, HCI and HCIIa. However, there was only a single HCI
      isoform in the hypertrophied soleus muscle. 5. These results indicate that
      overloading a skeletal muscle by removing its synergists produces not only the
      muscle hypertrophy but also the changes in the expression of MHC isoforms.

PMID- 8288031
TI  - Membrane-bound 5'-nucleotidase/nucleoside phosphotransferase from Bacillus
      cereus.
AB  - 1. A search for nucleoside phosphotransferase activity in Bacillus cereus led to
      the following results: (i) The phosphotransferase activity was associated with a
      membrane bound 5'-nucleotidase. (ii) The enzyme phosphorylates both purine and
      pyrimidine nucleosides as well as 2',3'-dideoxyinosine. (iii) The enzyme was
      inhibited by adenylic nucleotide di- and triphosphates, and its nucleotidase
      activity was increased in the presence of inosine as phosphate acceptor. 2.
      Bacterial and vertebrate 5'-nucleotidases with phosphotransferase activity differ
      for several characteristics, such as cellular location, substrate specificity,
      magnesium requirement and regulation.

PMID- 8288032
TI  - Effects of short chain fatty acid, sodium butyrate, on osteoblastic cells and
      osteoclastic cells.
AB  - 1. Sodium butyrate increased alkaline phosphatase (ALP) activity of cloned
      osteoblastic cell line MC3T3-E1 by the stimulation of de novo enzyme synthesis.
      2. Sodium butyrate did not affect mature osteoblastic cells but affected
      preosteoblastic cells. 3. Sodium butyrate decreased tartrate resistant acid
      phosphatase (TRACP)-positive multinucleated cells (MNC) formation from bone
      marrow cells. This related to the cytotoxicity of sodium butyrate on bone marrow
      cells.

PMID- 8288033
TI  - Isolation and properties of carboxylesterases of the termite gut-associated
      fungus, Xylaria nigripes. K., and their identity from the host termite,
      Odentotermes horni. W., mid-gut carboxylesterases.
AB  - 1. The termite, Odentotermes horni. W., houses three fungal species, viz. Xylaria
      nigripes, Termitomyces microcorpus, and Trichoderma (species not identified), in
      its gut. X. nigripes was found to possess higher esterase activity levels than
      the other two. 2. Four esterase enzymes, viz. FE-I, -II, -III and -IV, with pI
      values 5.1, 5.25, 5.4 and 5.6, respectively, were identified, isolated and
      purified to apparent homogeneity from the fungus X. nigripes, their biochemical
      and enzymological properties were determined, and compared with those of the
      previously characterized host termite mid-gut enzymes, TE-I and -II. 3. The M(r)
      of FE-I and -II was 85.1 kDa and those of FE-III and -IV was 87.5 kDa. However,
      TE-I and -II were relatively smaller (M(r) approximately 78.5 kDa). Each of the
      fungal enzymes, viz. FE-I to -IV, was a homodimer with subunits associated non
      covalently. The subunit M(r) were 42.6 kDa for FE-I and -II, and 43.7 kDa for FE
      III and -IV. On the other hand, the termite mid-gut enzymes, TE-I and -II, were
      also homodimeric, but the subunits were associated covalently (subunit M(r) = 40
      kDa). Immunologically the fungal esterase enzymes, viz. FE-I to -IV, were
      different from those of the host termite mid-gut esterases, viz. TE-I and -II. 4.
      The substrate specificity and inhibitor sensitivity studies classify these
      enzymes, i.e. FE-I to -IV, as carboxylesterases (EC 3.1.1.1). Steady-state
      product inhibition kinetics suggested; an ordered release of products, i.e.
      alcohol followed by acid, and a Uni-Bi kinetic reaction mechanism. 5. The two
      preliminary studies, i.e. the confinement of most esterase activity to the gut
      tissue free from microorganisms and starvation of termites not leading to
      complete loss of esterase activity in the gut of the termites, suggested that
      there may not be any symbiotic relationship between termite, O. horni, and its
      gut associated microorganisms with regard to ester metabolism. Though the enzymes
      from the two sources were carboxylesterases, several of their properties were
      different and hence, they are different entities.

PMID- 8288034
TI  - Analysis of human and bovine milk lactoferrins by Rotofor and chromatofocusing.
AB  - 1. Isoelectric points of human and bovine lactoferrins were evaluated by Rotofor
      and chromatofocusing analysis. 2. By Rotofor, the isoelectric value of human
      lactoferrin fraction was determined at 8.7 and that of bovine lactoferrin at 8.8.
      3. By chromatofocusing analysis, human and bovine lactoferrins showed different
      elution patterns. Human lactoferrin was eluted at pH 6.8-8 and bovine lactoferrin
      eluted at pH 8.2-8.9.

PMID- 8288035
TI  - Expression of P450 isoenzymes during rat liver organogenesis.
AB  - 1. The expression of P450 isoenzymes in foetal and neonatal hepatic microsomes
      was determined by measuring the metabolism of marker substrates and by studying
      the expression of P450 isoenzymes at the protein and mRNA level. 2. Monooxygenase
      activities were not measurable at day 10 of gestation, but shortly before birth
      (day 20 of gestation) and thereafter a surge in monooxygenase activities was
      observed using ethoxyresorufin, aniline, nitroanisole, aminopyrine,
      dimethylnitrosamine and aldrin as substrates. 3. In contrast, as early as day 10
      of gestation, post oxidative drug metabolism was measurable, when assessed for
      reactions catalysed by UDP-glucuronyltransferase, glutathione S-transferase and
      epoxide hydrolase. 4. Microsomal proteins isolated from foetal/perinatal rats did
      not crossreact with antibodies raised to CYP1A1, CYP1A2, CYP2A1, CYP2B1, CYP2E1,
      CYP3A1 and CYP4A1 at a protein loading of 3 micrograms total protein/well. 5.
      With the exception of CYP2E1 mRNA and CYP4A1 mRNA there was little evidence to
      suggest the expression of CYP1A1, CYP1A2 and CYP2A1 mRNA. 6. The mRNA of CYP2B1,
      CYP2C7 and CYP3A1 was not detectable in foetal/perinatal rat liver extracts at a
      loading rate of 10 micrograms total RNA. 7. Microsomal proteins isolated from
      neonatal rats crossreacted with antibodies raised to CYP2C6, CYP2E1, CYP3A1 and
      CYP4A1, albeit at varying intensities. 8. Concomitantly, CYP2A1, CYP2E1 and
      CYP4A1 mRNA transcripts were detectable in Northern blot hybridization
      experiments using neonatal rat liver RNA extracts.

PMID- 8288036
TI  - Identification of DNA adducts at specific locations by sequencing techniques.
AB  - 1. A simple procedure for the accurate identification of the positions of adduct
      formation when viral M13mp18 single stranded DNA is treated with
      chloroacetaldehyde (CAA) is presented. 2. The normal dideoxy sequencing reaction
      protocol was employed except no dideoxy nucleotides were used to cause chain
      termination. 3. Instead, the CAA adducted bases of the template DNA act as points
      of polymerase fall off causing the appearance of bands of DNA sequencing gel
      autoradiographs marking locations where adduct formation may have occurred.

PMID- 8288037
TI  - Molecular properties of aminopeptidase Ey as a zinc-metalloenzyme.
AB  - 1. Aminopeptidase Ey from hen's egg yolk contains 1.0 g atom of zinc/mol of a
      subunit having molecular weight of 150 kDa. The inactive, Zn(2+)-free apoenzyme
      was reactivated by Co2+, Mn2+, Ca2+, Cd2+, Cu2+ and Ni2+ in addition to Zn2+,
      whereas Mg2+ and Fe2+ were ineffective. 2. The enzymatical properties of
      reconstituted enzymes, except for Zn(2+)-reconstituted enzyme, differed from
      native enzyme. The values for the activation energy were calculated by
      aminopeptidase Ey and Co(2+)-reconstituted enzyme. 3. The isoelectric point of
      the enzyme was about 2.8 as determined by isoelectric focusing. An asialo form of
      the enzyme, obtained by treatment with Arthrobacter sialidase, had an isoelectric
      point of 4.4. 4. The amino terminal sequence of aminopeptidase Ey was determined
      to be acyl-Xaa-Xaa-Pro-Glu-Ala-Ala-Ser-Leu-Pro-Gly. There was no identity with
      any known sequences of aminopeptidase.

PMID- 8288038
TI  - Synthesis of dansyl ribonucleotides and their use in steady-state fluorescence
      anisotropy studies of nucleotide binding by initiation factor-2 (eIF-2) and
      histone H1.
AB  - 1. Fluorescent analogs of GDP and ATP were prepared with DANSYL-beta-alanine (D
      beta A) coupled to the (2')3' hydroxyl of the ribose. 2. Observation of changes
      in both total fluorescence and anisotropy accompanying the binding of D beta A
      GDP to eIF-2 allowed determination of Kd (33 nM). 3. When D beta A-ATP bound to
      H1 histone, the fluorescence quantum yield increased and the emission was blue
      shifted. Analysis yielded a Kd of 3.4 microM and 20 binding sites per histone. At
      high levels of ATP, fluorescence anisotropy values and light scattering
      intensities pointed to significant aggregation of H1 that is strongly dependent
      on ATP concentration.

PMID- 8288039
TI  - The aldose reductase controversy.

PMID- 8288040
TI  - Diazoxide causes recovery of beta-cell glucose responsiveness in 90%
      pancreatectomized diabetic rats.
AB  - Chronic hyperglycemia causes near-total disappearance of glucose-induced insulin
      secretion. The etiology has been suggested to be a nonsustainable stimulation of
      insulin release that causes beta-cells to become unresponsive to glucose through
      an undefined mechanism. We used an inhibitor of insulin secretion, diazoxide, to
      test this hypothesis in 90% pancreatectomized (Px) rats. Px rats were given 5
      days of diazoxide (30 mg/kg orally twice a day) or tap water starting on
      postoperative day 8, 15, or 22. In vitro pancreas perfusions were conducted 36 h
      posttreatment (2, 3, or 4 weeks after surgery) using a protocol of 15 min of 16.7
      mM glucose followed by 15 min of 16.7 mM glucose plus 10 mM arginine. In 2-week
      Px rats, insulin responses to 16.7 mM glucose and to glucose/arginine were both
      appropriate for the reduced beta-cell mass, i.e., no defect in beta-cell glucose
      responsiveness had yet occurred. Diazoxide had no affect on insulin release at
      this time. Between 2 and 3 weeks after pancreatectomy, insulin output to 16.7 mM
      glucose fell 75%, and that to glucose/arginine fell 50%. Diazoxide given at this
      time partially blocked the fall in glucose-induced insulin secretion and totally
      prevented that with arginine. The increased insulin secretion caused by diazoxide
      was accompanied by 1) lower nonfasting plasma glucose values, 2) improved glucose
      tolerance after oral glucose load, and 3) a 50% increase in pancreatic insulin
      content. Our results support the concept that excessive insulin secretion is a
      major cause of the hyperglycemia-induced loss of beta-cell glucose
      responsiveness. A leading candidate for the mechanism of this effect is depleted
      pancreatic insulin stores. Overstimulation of insulin secretion provides a new
      target for pharmacological therapy aimed at reducing glucose intolerance in non
      insulin-dependent diabetes mellitus.

PMID- 8288041
TI  - Dynamics of glucose production and uptake are more closely related to insulin in
      hindlimb lymph than in thoracic duct lymph.
AB  - We previously reported a striking similarity between the dynamics of both glucose
      turnover and thoracic duct lymph insulin during euglycemic clamps (J Clin Invest
      84:1620, 1989), which suggested that transendothelial insulin transport (TET) is
      rate-limiting for insulin action in vivo. Thoracic duct lymph, however, is
      primarily derived from insulin-insensitive tissues, which raises questions as to
      the physiological significance of this relationship. The relationship between
      glucose turnover and TET was thus examined in insulin-sensitive tissues by the
      simultaneous measurement of insulin in plasma, thoracic duct lymph, and hindlimb
      lymph during euglycemic clamps in normal anesthetized dogs (n = 8). Clamps
      consisted of two 3-h phases: a 0.6 mU.min-1.kg-1 insulin infusion (activation
      phase) followed by termination of the insulin infusion (deactivation phase).
      Lymph insulin was less than plasma insulin during both phases (P < 0.01) with
      steady-state hindlimb (120 +/- 12 pM) and thoracic duct lymph insulin (138 +/- 12
      pM) 38 and 45%, respectively, lower than steady-state plasma insulin (222 +/- 24
      pM) at the end of the activation phase (P < 0.05). Also, the rate of increase of
      lymph insulin was slower than plasma insulin during hormone infusion; half-time
      to steady-state was 8.8 +/- 2.0 min for plasma insulin, but longer for thoracic
      (25.8 +/- 3.5) and hindlimb lymph insulin (40.7 +/- 5.7 min). A very close
      relationship was observed during activation between the rate of increase of
      glucose uptake (Rd) and the increase in hindlimb lymph insulin (r2 = 0.92); this
      relationship was weaker for thoracic lymph (r2 = 0.74) and much weaker between
      glucose uptake and plasma insulin (r2 = 0.35). These data support the concept
      that interstitial insulin (represented by hindlimb lymph) is the signal that
      determines glucose uptake by insulin-sensitive tissues and that the rate of
      increase of glucose uptake is determined by transendothelial insulin transport
      into insulin-sensitive tissue. Also, during activation, hindlimb lymph insulin
      was a very strong predictor of the rate of suppression of hepatic glucose output
      (HGO) (r2 = 0.96), and the correlation with HGO was stronger than that for
      thoracic lymph (r2 = 0.85). The evidence that the rate of increase of Rd and the
      rate of suppression of HGO during insulin infusion are very strongly predicted by
      the time course of insulin in hindlimb lymph is consistent with the single
      gateway hypothesis: the insulin transport rate across endothelium in insulin
      sensitive tissue (skeletal muscle) determines the rate of glucose utilization and
      the suppression of hepatic glucose output.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8288042
TI  - Muscle sympathetic nerve activity in response to glucose ingestion. Impact of
      plasma insulin and body fat.
AB  - Carbohydrate intake stimulates sympathetic nervous system activity in lean
      subjects, whereas in obese subjects, the results have been inconsistent. The aim
      of this study was to directly measure sympathetic neural outflow to skeletal
      muscle in response to a 75-g oral glucose tolerance test (OGTT) in 15 Pima Indian
      and 16 Caucasian men, matched for body fat and age, but covering a large range of
      body weight (57-113 kg) and body fat (4-41%). Fasting muscle sympathetic nerve
      activity (MSNA) correlated positively with body fat (r = 0.73; P = 0.001) in
      Caucasians but not in Pima Indians, whereas the increase in MSNA during the OGTT
      correlated negatively with the percentage of body fat (r = -0.38, P = 0.03)
      independently of race. In each subject, the increase in MSNA over time correlated
      positively with the increase in plasma insulin levels, but the slopes of these
      relationships were inversely related to the percentage of body fat (r = -0.52, P
      = 0.003) independently of race. In conclusion, obesity is associated with a
      higher fasting sympathetic neural outflow to muscle but a blunted increase in
      response to an oral glucose load despite a larger increase in plasma insulin
      levels. This blunted response may represent another feature of the
      obesity/insulin resistance syndrome.

PMID- 8288043
TI  - Islet-specific T-cell clones from the NOD mouse respond to beta-granule antigen.
AB  - Islet-reactive T-cell clones from NOD mice provide an important approach to the
      investigation of antigens with relevance to type I diabetes. To identify a source
      of beta-cell antigen suitable for biochemical studies, we have used two islet
      specific, diabetogenic T-cell clones to test beta-tumor cells. beta-tumor cell
      lines, maintained in continuous culture, were found to lose antigenicity rapidly.
      However, cells harvested directly from beta-tumors arising spontaneously in the
      transgenic NOD/Lt-Tg(RIPTag)1Lt mouse proved to be a potent source of beta-cell
      antigen for the T-cell clones. Subcellular fractionation of beta-tumor cells
      showed that the T-cell antigen was highly enriched in the beta-granule fraction
      and that this activity was associated with the granule membrane.

PMID- 8288044
TI  - Pioglitazone increases insulin sensitivity, reduces blood glucose, insulin, and
      lipid levels, and lowers blood pressure, in obese, insulin-resistant rhesus
      monkeys.
AB  - The antidiabetic effects of pioglitazone hydrochloride were evaluated in 6
      spontaneously obese, insulin-resistant rhesus monkeys. The animals were studied
      during six successive 2-wk treatment phases separated by 2-wk rest periods: two
      placebo phases; 0.3, 1.0, and 3.0 mg.kg-1 x day-1 pioglitazone hydrochloride
      phases; and a final placebo phase. During the second week of each treatment
      phase, serum insulin (immunoreactive insulin [IRI]), plasma glucose, and serum
      triglyceride (TG) levels were measured after an overnight fast and after a
      standardized meal. Blood pressure was measured and glucose tolerance tests
      (modified minimal model protocol) were performed a few days after the meal tests.
      Pioglitazone hydrochloride significantly improved fasting and postprandial levels
      of IRI, plasma glucose, and TG in a dose-related manner (P < 0.05). Fasting
      values during treatment with 3.0 mg.kg-1 x day-1 were reduced by 64% for IRI, 19%
      for plasma glucose, and 44% for TG compared with the placebo phase before
      treatment. Efficacy of pioglitazone hydrochloride was more marked for those
      animals with fasting hyperglycemia. Insulin sensitivity was increased by
      pioglitazone hydrochloride (P = 0.05), whereas glucose effectiveness and glucose
      disappearance rate were not detectably affected. Systolic and mean arterial blood
      pressures were significantly decreased by pioglitazone hydrochloride (P < 0.05).
      No toxic side effects of pioglitazone hydrochloride treatment were noted.

PMID- 8288045
TI  - Insulin resistance, body fat distribution, and sex hormones in men.
AB  - Although many studies have suggested that increased androgenicity is associated
      with insulin resistance and hyperinsulinemia in both pre- and postmenopausal
      women, relatively few data are available on this relationship in men. We examined
      the association of body mass index (BMI), waist-to-hip ratio (WHR), sex hormone
      binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone
      sulfate (DHEA-SO4), and estradiol with insulin concentrations and whole-body
      glucose disposal in 87 men from a population-based study in Kuopio, Finland. BMI
      was significantly correlated with fasting insulin (r = 0.46), total whole-body
      glucose disposal (r = -0.30), glucose oxidation (r = -0.21), and nonoxidative
      glucose disposal (r = -0.25). WHR also was significantly associated with fasting
      insulin (r = 0.61), total whole-body glucose disposal (r = -0.54), glucose
      oxidation (r = -0.23), and nonoxidative whole-body glucose disposal (r = -0.50).
      SHBG and total and free testosterone were significantly associated with insulin
      concentrations and total and nonoxidative glucose disposal but not with glucose
      oxidation. DHEA-SO4 and estradiol were not associated with insulin, glucose
      concentrations, or whole-body glucose disposal in univariate analysis. In
      multivariate analysis, total whole-body glucose disposal was associated
      negatively with WHR and positively associated with total testosterone and SHBG;
      nonoxidative whole-body glucose disposal was associated negatively with WHR and
      positively associated with total and free testosterone. Glucose oxidation was
      significantly associated only with WHR. In conclusion, higher WHR and lower
      testosterone were strongly associated with a decrease in total and nonoxidative
      whole-body glucose disposal in men.

PMID- 8288046
TI  - Higher maternal than paternal inheritance of diabetes in GK rats.
AB  - Results from crosses between Goto-Kakizaki (GK) rats, which exhibit spontaneous
      non-insulin-dependent diabetes mellitus (NIDDM), and outbred nondiabetic Wistar
      rats have demonstrated an effect of maternal inheritance on diabetes in offspring
      of the first generation (F1). At 6 weeks of age, F1 offspring of sex-directed
      crosses exhibited plasma glucose values intermediate between GK and Wistar
      parents. Hyperglycemia in F1 rats born of female GK rats (F1GK) was more marked
      than in those born of female Wistar (F1W) rats. At 3 months of age, F1 rats
      showed a marked impairment of both glucose tolerance and insulin secretion, which
      was intermediate between GK and Wistar rats. Glucose intolerance was more
      pronounced in F1GK rats than in F1W. By contrast, insulin secretion in F1W rats
      was more deteriorated than in F1GK rats. No deletion in mitochondrial DNA was
      observed in the GK rats, which decreased the possibility of a mitochondrial
      inheritance effect as an explanation of our findings. These data support a
      polygenic model in diabetes inheritance of NIDDM and suggest that, in addition to
      genetic factors, a perturbed maternal metabolism can contribute to its
      inheritance.

PMID- 8288047
TI  - Skeletal muscle vascular transport capacity in diabetic rats.
AB  - This study aimed to determine the effect of long-term (17-20 weeks) streptozocin
      (STZ)-induced diabetes on skeletal muscle vascular transport capacity. Vascular
      transport capacity was determined from measurements of pressure-flow
      relationships, capillary filtration coefficient, and permeability-surface area
      product (PS) for 51Cr-EDTA in isolated perfused hindquarters of control (n = 7)
      and diabetic (n = 6; 65 mg/kg STZ intraperitoneally) rats. Hindquarters were
      perfused with Tyrode's solution containing albumin (5 g/dl) and horse serum (10%
      vol/vol) and were maximally vasodilated with papaverine (30 mM). Hindquarters of
      diabetic rats weighed 42% less than control rats (86 +/- 3 vs. 147 +/- 4 g; P <
      or = 0.001) because of profound muscle atrophy. Total hindquarters flow (ml.min-1
      x 100 g-1) was greater in diabetic rats (P < 0.001) at perfusion pressures
      between 23 and 75 mmHg, indicative of an increased flow capacity relative to
      control rats. However, absolute flows (ml/min) were not different between control
      and diabetic rats. Neither capillary filtration coefficient (control = 0.0243 +/-
      0.0010 and diabetic = 0.0297 +/- 0.0024 ml.min-1 x mmHg-1 x 100 g-1) nor
      isogravimetric PS (control = 3.91 +/- 0.31 and diabetic = 4.39 +/- 0.46 ml.min-1
      x 100 g-1) were different in control and diabetic rats. However, absolute values
      for capillary filtration coefficient (ml.min-1 x mmHg-1) and PS (ml/min) were
      less in diabetic rats. These results indicate that muscle atrophy in rats with
      STZ-induced diabetes is accompanied by a proportional reduction in absolute
      exchange capacity for water (capillary filtration coefficient) and small solutes
      PS, such that microvascular exchange capacity per tissue mass is maintained at
      control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288048
TI  - Mutational analysis of the NH2-terminal glycosylation sites of the insulin
      receptor alpha-subunit.
AB  - The insulin receptor is synthesized as a single chain of 190 kiloDaltons, which
      is processed to disulfide-linked mature alpha- and beta- subunits, containing N-
      and O-linked oligosaccharides and fatty acids. Previously (Collier E, Carpentier
      J-L, Beitz L, Caro LHP, Taylor SI, Gorden P: Biochemistry 32:7818-23, 1993), site
      directed mutagenesis of the asparagine in the first four sites of N-linked
      glycosylation to glutamine resulted in a receptor that was retained in the
      endoplasmic reticulum and not processed past the proreceptor form. In this study,
      mutation of these sites individually and in various combinations is studied.
      Mutation in the first or second glycosylation site does not significantly impair
      processing of the receptor; the receptor is found on the cell surface and binds
      insulin normally. If both the first and second sites are mutated, a significant
      reduction occurs in the amount of receptor found on the cell surface and in
      insulin binding. There is some processing of the receptor in cells expressing
      this mutant compared with the four-part mutant. If only the third and fourth
      sites are mutated, processing is impaired less than in the mutant with the first
      and second sites mutated. However, the amount of receptor found on the cell
      surface is less than in the mutant of only the first or only the second site. In
      all of these glycosylation mutants, the amount of receptor on the cell surface
      correlates with the level of 125I-labeled insulin binding on the cell
      surface.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288049
TI  - Prevalence of mutations in the insulin receptor gene in subjects with features of
      the type A syndrome of insulin resistance.
AB  - Mutations of the insulin receptor gene are a cause of the type A syndrome of
      extreme insulin resistance. This study assessed the prevalence of such mutations
      in women with clinical features of the type A syndrome including ovarian
      hyperandrogenism, moderate-to-severe degrees of insulin resistance, and
      acanthosis nigricans. We studied 22 unrelated women with insulin resistance
      (fasting insulin > 300 pM [50 microU/ml] and/or peak during an oral glucose
      tolerance test (OGTT) > 1,800 pM [300 microU/ml]), acanthosis nigricans, and the
      polycystic ovary syndrome (hyperandrogenemia, oligoamenorrhea, and hirsutism).
      Two insulin-resistant probands with congenital generalized lipodystrophy and one
      male proband with severe insulin resistance also were included in the study.
      Southern blotting experiments were performed to exclude gross gene deletions,
      insertions, or rearrangements. Exons 2-22 of the insulin receptor gene were
      polymerase chain reaction (PCR) amplified from genomic DNA and screened for
      nucleotide variation using single-strand conformation polymorphism (SSCP). No
      nucleotide variation between study subjects was detected in exons 4-6, 10-12, 15,
      16, 18, 19, or 21. Sequencing of amplified DNA revealed that SSCP variants in
      exons 2, 3, 8, 9, and 17 corresponded to known silent polymorphisms within the
      coding region. Variants in exons 2, 9, 13, and 14 were caused by novel silent
      polymorphisms; variants in exons 7 and 22 were caused by nucleotide substitutions
      in flanking introns. One proband was found to have a heterozygous point mutation
      in exon 20 (CGG-->CAG, Arg1174-->Gln) that involves the intracellular receptor
      beta-subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288050
TI  - Suppression of gluconeogenesis after a 3-day fast does not deplete liver glycogen
      in patients with NIDDM.
AB  - To determine the effect of inhibition of gluconeogenesis on liver glycogen stores
      in patients with non-insulin-dependent diabetes mellitus (NIDDM) after a 3-day
      fast, 10% ethanol (EtOH) was administered intravenously to nine obese patients
      with NIDDM and six obese nondiabetic subjects. Rates of glucose appearance (3
      [3H]glucose) and [U-14C]alanine incorporation into glucose (alanine
      gluconeogenesis [Ala-GNG]) were determined before and during EtOH administration,
      and residual glycogen stores were assessed by the incremental glucose response to
      glucagon (glucoseAUC). Hepatic glucose output (HGO) was closely correlated with
      plasma glucose levels (r = 0.71, P < 0.001) after the 3-day fast and was
      significantly greater in the diabetic compared with the nondiabetic subjects
      (13.8 +/- 1.4 vs. 7.6 +/- 0.6 mumol.kg-1 FFM.min-1, P < 0.01). During the 120-min
      EtOH infusion, Ala-GNG fell by more than 50% in both groups and did not increase
      after intravenous glucagon administration. HGO fell modestly in both the diabetic
      and nondiabetic subjects during the first 30 min of EtOH infusion and stabilized
      thereafter. In contrast to Ala-GNG, HGO increased significantly after intravenous
      glucagon administration in both the diabetic and nondiabetic subjects, but the
      increase was significantly greater in the patients with NIDDM (P < 0.01). The
      glucose area under the curve in response to glucagon (glucoseAUC) was lower in
      the presence of EtOH than in its absence (14.9 +/- 7 vs. 68 +/- 15.6 mM/min, P <
      0.01) in the obese nondiabetic subjects, which suggests a decrease in liver
      glycogen stores.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288051
TI  - Enzyme-linked immunosorbent assay method for human autophosphorylated insulin
      receptor. Applicability to insulin-resistant states.
AB  - The insulin receptors from erythrocytes of 50 patients with non-insulin-dependent
      diabetes mellitus were tested for their ability to autophosphorylate. The assay
      was performed by a new enzyme-linked immunosorbent assay system that used
      monoclonal anti-insulin receptor antibodies absorbed to microtiter plates as a
      first antibody and polyclonal antiphosphotyrosine antibody as a labeled second
      antibody. By this assay, 3 patients were identified with defects in their insulin
      receptor kinase, although their defects appeared heterogeneous. Patient 1 had 85%
      less maximal autophosphorylation with a normal ED50 (1.6 x 10(-9) M insulin).
      Patient 2, who had polycystic ovary disease, had a 49.2% decrease in maximal
      autophosphorylation of insulin receptors, and the ED50 was shifted to the right
      (5.6 x 10(-8) M). Patient 3 with acanthosis nigricans had a normal maximal
      autophosphorylation, but the ED50 shifted to the right (2.9 x 10(-8) M). The
      mechanisms for the diversity detected in this assay is not known, but this
      technique has sufficient specificity and sensitivity to be used to screen for
      insulin-resistant patients who have a lack of kinase activity.

PMID- 8288052
TI  - Impact of diabetic inheritance on glucose tolerance and insulin secretion in
      spontaneously diabetic GK-Wistar rats.
AB  - The impact of genetic factors and maternal diabetes on glucose tolerance and
      pancreatic beta-cell function was studied in first generation (F1) offspring
      generated in crosses between the spontaneously diabetic Goto-Kakizaki (GK)-Wistar
      rat and normoglycemic control Wistar rats (W). The (GK x W) F1 hybrids were
      offspring of either male GK (mGK) and female Wistar (fW) (mGK x fW) or male
      Wistar (mW) and female GK (fGK) (mW x fGK) rats. Already at 8 days of age, blood
      glucose levels were elevated in GK (7.6 +/- 0.5 vs. 4.8 +/- 0.3 mM in W; P <
      0.001) and in F1 rats (6.0 +/- 0.3 in mGK x fW and 6.6 +/- 0.4 mM in mW x fGK;
      both P < 0.01 vs. W). In 2-month-old male rats, glucose (2 g/kg,
      intraperitoneally) markedly increased blood glucose levels after 60 min in GK
      rats (18.1 +/- 0.6 vs. 5.5 +/- 0.3 mM in W; P < 0.001) and moderately increased
      levels in F1 rats (9.9 +/- 0.9 in mGK x fW and 11.6 +/- 1.0 mM in mW x fGK, both
      P < 0.01 vs. W). Similar patterns were obtained in female rats. Repeated
      backcrossing of F1 with W rats successively improved glucose tolerance. In
      perfused pancreases of male rats, the 20-min insulin response to 16.7 mM glucose
      was -7.44 +/- 5.18 pmol in GK rats, 71.57 +/- 12.25 pmol in W rats, 9.00 +/- 0.89
      pmol in mGK x fW rats, and 18.20 +/- 3.97 pmol in mW x fGK rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8288053
TI  - Assessment of insulin action in NIDDM in the presence of dynamic changes in
      insulin and glucose concentration.
AB  - Both glucose and insulin are important regulators of glucose uptake and hepatic
      glucose release. Because insulin concentrations rarely if ever increase under
      daily living conditions, unless glucose concentrations also increase, we sought
      to determine whether hepatic and extrahepatic responses to changes in insulin and
      glucose concentration are impaired in patients with non-insulin-dependent
      diabetes mellitus (NIDDM). To address this question, glucose metabolism was
      measured in diabetic and nondiabetic subjects. A computer-driven infusion system
      was used to produce a nondiabetic postprandial insulin profile in both groups
      while sufficient exogenous glucose was infused to mimic nondiabetic postprandial
      glucose concentrations. Although NIDDM was associated with greater (P < 0.05)
      hepatic glucose release both before and during the prandial insulin infusion,
      suppression did not differ in the diabetic and nondiabetic subjects (-1.06 +/-
      0.20 vs. -0.86 +/- 0.15 mmol/kg every 4 h). In contrast, stimulation of both
      glucose disappearance (0.77 +/- 0.27 vs. 1.68 +/- 0.27 mmol/kg every 4 h) and
      forearm glucose uptake (187 +/- 81 vs. 550 +/- 149 mumol/dl every 4 h) was lower
      (P < 0.05) in diabetic than in nondiabetic subjects. Thus, despite increased
      basal rates of glucose production, obese individuals with NIDDM had decreased
      stimulation of glucose disappearance but normal suppression of hepatic glucose
      release in response to nondiabetic prandial glucose and insulin concentrations.
      These data indicate that the increase in glucose that occurs with carbohydrate
      ingestion is likely to compensate for hepatic but not extrahepatic insulin
      resistance.

PMID- 8288054
TI  - Insulin degradation in vitro and in vivo: a comparative study in men. Evidence
      that immunoprecipitable, partially rebindable degradation products are released
      from cells and circulate in blood.
AB  - The products of insulin metabolism generated in vitro and in vivo were compared
      in this study. Monocytes from 10 control subjects were incubated with 125IA14
      labeled insulin, acid washed, and solubilized or reincubated in insulin-free
      binding buffer to study both intracellular radioactivity or radioactivity
      released from cells to medium. To evaluate in vivo insulin metabolism, labeled
      insulin (100-120 microCi) was injected as a single intravenous bolus in 5 of the
      10 subjects. Cellular and plasma radioactivity was characterized by high
      performance liquid chromatography (HPLC). The results of the study show the
      following: 1) Products with superimposable HPLC elution profiles are found within
      cells and in medium. Two new labeled products are observed in the latter,
      suggesting that a membrane degradation process exists in monocytes. 2)
      Intermediates found within monocytes, in medium from monocytes, and in plasma
      have identical elution profiles, supporting the possibility that insulin is
      metabolized in various cells by a common pathway. 3) Insulin metabolism produces
      intermediates that bind well to anti-insulin antibody. The presence in plasma of
      these products induces a significant difference in the value of the metabolic
      clearance rate of insulin when HPLC or immunoprecipitation is used to detect
      intact insulin. 4) Immunoprecipitable products maintain, in part, the capacity to
      bind to insulin receptors and to be internalized into monocytes.

PMID- 8288055
TI  - An upstream element from the human insulin receptor gene promoter contains
      binding sites for C/EBP beta and NF-1.
AB  - We have shown previously that a 500-bp region of the human insulin receptor
      promoter (-0.3 to -1.8 kb) was able to stimulate transcription from a
      heterologous thymidine kinase promoter in HepG2 hepatoma cells but not in HeLa
      fibroblasts. Footprint analysis localized the transcription factor binding sites
      to a 36-bp region at -1420. In this paper, we analyze the factors that recognize
      this element and show that it contains binding sites for the CAAT/enhancer
      binding protein C/EBP and nuclear factor 1 (NF-1). In addition we show that both
      C/EBP alpha and the C/EBP beta can transactivate the human insulin receptor
      promoter in a dose-dependent manner.

PMID- 8288056
TI  - Mortality and treatment side-effects during long-term intensified conventional
      insulin treatment in the Stockholm Diabetes Intervention Study.
AB  - Altogether, 102 patients were randomized to intensified conventional treatment
      (ICT) (n = 48) or standard treatment (ST) (n = 54). After 7.5 years, 89 patients
      remained, and it was shown that microangiopathy was retarded by the lower blood
      glucose concentrations seen in the patients in the ICT group. HbA1c was reduced
      from (means +/- SE) 9.5 +/- 0.2% to 7.1 +/- 0.1% in the ICT group and from 9.4 +/
      0.2% to 8.5 +/- 0.1% in the ST group (P < 0.001). Of the patients, 4 in the ICT
      group and 3 in the ST group died. Mortality was predicted by albuminuria, the
      amplitude of the sural nerve action potential, and the test of arm blood flow
      during contraction of the contralateral hand (sympathetic nerve function) at
      baseline (P < 0.05). Weight increased by 4.4 +/- 1.1 kg in the ICT group and 1.8
      +/- 0.7 kg in the ST group (P = 0.05). Atherosclerosis, measured with digital
      pulse plethysmography, was approximately the same in the groups at baseline and
      after five years. In each group, 3 patients had myocardial infarctions, and 2
      from each group had ketoacidosis once. There was a mean of 1.1 episodes per
      patient and per year of serious hypoglycemia in the ICT group and 0.4 episodes
      per patient and per year in the ST group. No adverse incidents or accidents were
      observed in either group, and there were no differences between the groups with
      regard to cognitive function measured with a battery of tests.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8288057
TI  - Effect of NIDDM on the kinetics of whole-body protein metabolism.
AB  - We postulated that dietary protein utilization and body protein metabolism are
      altered in hyperglycemic individuals with non-insulin-dependent diabetes mellitus
      (NIDDM). This was tested by estimating the kinetics of protein metabolism in
      obese NIDDM patients in the hyperglycemic state of isoenergetic feeding and in
      the normoglycemic state induced by the prolonged use of a very-low-energy diet
      (VLED) and comparing them with results in obese nondiabetic subjects studied
      previously. Seven obese subjects with NIDDM (one male, six females, body mass
      index = 35.8 +/- 2.0 kg/m2) were given a 1.7 MJ (410 kcal) all protein (93 g/day)
      diet derived from hydrolyzed collagen and supplemented with tryptophan and
      methionine, which provides 16% of its amino acids as essential, a multivitamin
      and mineral supplement, and 16 mmol KCl for 42 days. During the seven-day
      isoenergetic diet and at weeks 4 and 6 of the VLED, amino nitrogen (N) flux rate
      was calculated from the urine [15N]urea enrichment by using the 60-h oral
      [15N]glycine method to obtain the integrated feeding-fasting metabolism. Rates of
      synthesis (S) and breakdown (B) were calculated from N flux. At day 7 of the
      isoenergetic diet, whole-body N flux, S, B, and resting metabolic rate (RMR) were
      12-24% greater (P < 0.05) in the NIDDM subjects than observed in nondiabetic
      obese subjects. Mean plasma glucose decreased (P < 0.05) from the isoenergetic
      period (14.9 +/- 2.4 mM) to 7.2 +/- 1.2 mM at week 4 and 6.5 +/- 1.1 mM at week 6
      of the VLED. RMR declined progressively by 25% at week 5 of the VLED.
      Corresponding significant (P < 0.05) decreases from isoenergetic feeding to weeks
      4 and 6 of the VLED occurred in whole-body N flux (from 51 +/- 2 to 42 +/- 1 g
      N/day), in S (from 38 +/- 3 to 24 +/- 1 g N/day), and in B (from 39 +/- 3 to 26
      +/- 1 g N/day) resulting in net losses (S-B). S-B was significantly more negative
      (P < 0.05) in NIDDM than in the nondiabetic obese subjects at week 4 (-1.5 +/-
      0.5 vs. 0.9 +/- 0.3 g N/day) but not at week 6 (-1.3 +/- 0.4 vs. -0.9 +/- 4 g
      N/day). During the VLED, N balance became less negative with time but never
      reached equilibrium in NIDDM. Thus, abnormal protein metabolism is present in
      NIDDM in the isoenergetic fed state with moderate hyperglycemia and persists
      during a VLED that restores glycemia to near normal.

PMID- 8288058
TI  - Islet amyloid polypeptide in human insulinomas. Evidence for intracellular
      amyloidogenesis.
AB  - Amyloid deposits that characteristically form in the pancreatic islets of
      patients with non-insulin-dependent diabetes mellitus (NIDDM) and in insulinomas
      are both derived from islet amyloid polypeptide (IAPP). Evidence from previous
      studies has suggested that deposition of IAPP-derived amyloid is related to
      inherent amyloidogenic sequences present within normal human IAPP, together with
      an increased production and local concentration of IAPP. However, whether the
      aggregation of IAPP to form amyloid fibrils is primarily an intra- or
      extracellular event is not clear. To address this question, we studied 20 human
      insulinomas by light and electron microscopy. By light microscopy, amyloid
      deposits were demonstrated in 13 of 20 (65%) human insulinomas. Furthermore,
      evaluation of Congo red-stained tumor sections showed small, globular or
      irregular, congophilic amyloid deposits within the cytoplasm of many tumor cells
      in 10 of 13 (77%) amyloid-containing insulinomas. Dense, punctate areas of IAPP
      immunoreactivity within tumor cells corresponded with the congophilic
      intracellular deposits. Ubiquitin immunoreactivity also was observed as punctate
      intracellular labeling and within large extracellular amyloid deposits. Among the
      10 insulinomas available for electron microscopic evaluation, pathological IAPP
      immunoreactive (immunogold) deposits were found in 3 of 5 insulinomas in which
      amyloid was demonstrated by light microscopy and in none of 5 tumors found
      negative for amyloid by light microscopy. Morphology of IAPP-immunoreactive
      deposits varied from those with the classical distinct 7- to 10-nm diameter
      nonbranching fibrils to those with distinct but faint fibrillarity to those
      without discernable fibrils.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288060
TI  - Debate on the MIST syndrome.

PMID- 8288059
TI  - Aldose reductase inhibition and retinopathy.

PMID- 8288061
TI  - Manuscript review in Family Medicine.

PMID- 8288062
TI  - A call for in-depth qualitative research on career choices.

PMID- 8288063
TI  - Behavioral science component of the fourth-year clerkship.

PMID- 8288064
TI  - Working with the "problem" resident: guidelines for definition and intervention.
AB  - Clinical teachers often work with residents whom they view as "difficult." For
      some, it is a knowledge deficit that first alerts them to a problem; for others,
      it is an attitudinal problem or distressing behavior. The goal of this article is
      to describe a framework for identifying residents' problems and to outline
      strategies for intervention. When teachers first suspect a problem, they should
      try to define the resident's troubling behavior, assess other contributing
      factors, and evaluate the potential impact of the problem. Following this initial
      process, teachers should try to confirm their suspicions by determining the
      resident's perception of the problem, relevant life history, and perceived
      strengths and weaknesses. They should also examine their own strengths and
      weaknesses and obtain other teachers' views of the perceived difficulty. In
      designing an intervention, teachers should carefully define the goal and time
      frame of the intervention, determine how the problem will be addressed, and
      decide how the intervention will be documented and evaluated. Although residents'
      difficulties are often seen as residing within the resident alone, teacher and
      systems factors must be considered, and the resident should be involved in every
      step of the process.

PMID- 8288065
TI  - Reality shock: a case study in the socialization of new residents.
AB  - For the graduating medical student, the transition from medical school to
      residency can be stressful. Although much has been written about resident stress,
      little attention has been directed to the socialization process of medical
      students entering a residency program. This case report describes a difficult
      experience with the socialization of a class of new family practice residents. A
      model of professional socialization called "reality shock" is presented.
      Strategies and educational interventions aimed at helping overcome reality shock
      are described.

PMID- 8288066
TI  - A prerogatives-based model for assessing and managing the resident in difficulty.
AB  - This paper describes a comprehensive, well-tested approach to managing residents
      with vexing noncognitive performance and attitudinal difficulties. Frustrations
      surrounding such cases often stem from inadequately defining and acknowledging
      the boundaries of faculty and resident prerogatives. Conceptual order is brought
      to these ill-structured problems by dividing nonroutine assessment into two
      cycles; a work-up cycle for suspected problems in which the resident is the
      primary decision maker, and a probation cycle for more serious issues in which
      faculty are the primary decision makers. By replacing adversarial positioning
      with a "let's find out" approach, the model encourages faculty to raise suspected
      issues early while supporting resident autonomy and professional responsibility.
      Finally, it recognizes the absolute discretion of faculty to judge trainee
      performance, to impose special requirements, or to terminate a resident's
      contract for cognitive or noncognitive deficiencies. Application of the model is
      illustrated through sample dialogues.

PMID- 8288067
TI  - Survey of family medicine residents evaluation methods.
AB  - BACKGROUND: Family medicine residents are evaluated to ensure mastery of required
      practice skills by a variety of methods. The objective of this paper is to report
      the results of a sample of the 394 accredited family practice residencies to
      determine the evaluation methods used and their corresponding value to the
      program. METHODS: Questionnaires were sent to program directors and chief
      residents of all accredited family practice residency programs. RESULTS:
      Responses were received from the director or chief resident of 354 (90%)
      programs. For 195 programs, both the chief resident and program director
      responded. The five most common evaluation methods were the American Board of
      Family Practice In-Training Examination, formative review sessions, resident
      chart review, list of procedures performed, and family medicine conference
      attendance. Of 195 programs for which directors and chief residents both
      responded, directors and chief residents differed significantly in the reported
      number of evaluation methods but not in perceived value of those evaluation
      methods. Neither geographic region, community or university affiliation, class
      size, nor age of program was associated with differences in numbers of evaluation
      methods or perceived value of those methods. CONCLUSION: Many highly rated
      resident evaluation methods are being utilized by less than one-third of the
      programs. The most prevalent forms of evaluation appear to be auditing medical
      practices and behaviors.

PMID- 8288068
TI  - The evaluation of family practice residents: a national survey.
AB  - BACKGROUND: There is a significant lack of information regarding the evaluation
      of family practice residents. METHODS: A questionnaire was sent to all 397 family
      practice residency directors in the United States to determine the methods used
      in evaluating family practice residents. RESULTS: Seventy-nine percent of
      residency directors returned the survey. Family practice faculty are involved in
      the majority of resident evaluations and are trained in the evaluation process in
      46% of the programs. The most common evaluation method was a written form
      completed in 99% of the programs for inpatient evaluations and in 67% for
      outpatient evaluations. The evaluation forms were five years or older in 30% of
      the programs and were rotation specific in 40% of the programs. Other evaluation
      methods included videotaping, peer and self-evaluations, and structured clinical
      examinations. CONCLUSIONS: Faculty development in evaluation performance is
      strongly encouraged. Written evaluation forms are used extensively, but the
      quality of these forms remains unknown. Further investigations into appropriate
      family practice evaluation methods are recommended.

PMID- 8288069
TI  - Not just teaching, not quite therapy.

PMID- 8288070
TI  - When is a test positive? The use of decision analysis to optimize test
      interpretation.
AB  - Clinical laboratory are often provided as numerical values that are then
      interpreted as being positive or negative. While this approach might simplify
      interpretation, it also makes interpretation contingent on a standard test cutoff
      point. Alternatively, test results can be interpreted for a specific patient with
      reference to the particular patient's probability of disease, the benefit of
      detecting disease when it is present, and the cost of mistakenly making the
      diagnosis when the disease is a absent. This paper explains the analysis of
      laboratory test results using techniques from decision analysis and receiver
      operator characteristic (ROC) curve analysis to define a positive result. The
      relationship between the ROC curve and likelihood ratios is illustrated using the
      diagnosis of urinary tract infection (UTI) to illustrate these concepts.

PMID- 8288071
TI  - Withdrawing long-term diuretic therapy in the elderly: a study in general
      practice in The Netherlands.
AB  - BACKGROUND: About 20% of all men and women age 65 or older are on maintenance
      therapy with diuretics. Multiple drug use and side effects increase with age
      whereas a clear indication for long-term diuretic therapy is not always present.
      The aim of the present study was to assess whether in some patients long-term
      diuretic therapy could be withdrawn in general practice. METHODS: This study is a
      pilot-study for a large multicentered randomized controlled trial in general
      practice. In one general practice in The Netherlands, 15 diuretic-using patients
      were selected from a total population of 52. All had been using diuretics for
      more than six months, were not hypertensive, and did not show overt symptoms of
      heart failure. In these 15 patients, diuretic medication was withdrawn under
      careful medical monitoring conditions. RESULTS: After six months, six patients
      were still without diuretic therapy. Diuretic therapy had to be resumed in nine
      cases, because of congestive heart failure (one), hypertension (three), bronchial
      asthma (one), increased ankle edema (two) and subjective complaints (two). The
      withdrawal of diuretic therapy caused an increase in mean systolic blood
      pressure, heart failure score, body weight and ankle edema. CONCLUSIONS: Long
      term maintenance diuretic therapy in patients age 65 or older in general practice
      may be successfully withdrawn in selected cases. Careful medical surveillance
      during and after withdrawal is warranted.

PMID- 8288072
TI  - Alternate career choices of medical students: their relationship to choice of
      specialty.
AB  - BACKGROUND AND METHODS: To help identify additional information regarding why
      some individuals are more likely to enter certain medical specialties, we
      undertook a study to evaluate the relationship between a senior medical student's
      self-reported alternate career choice (ie, if he or she had not entered
      medicine), and that student's subsequent choice of a medical specialty. RESULTS:
      Students entering the specialties of pediatrics, family practice, obstetrics and
      gynecology, and emergency medicine were likely to have chosen alternate careers
      in the teaching, health care, humanities, arts, and nonprofessional areas. In
      contrast, students entering the specialties of anesthesiology, radiology,
      internal medicine, and surgery (general surgery or the surgical subspecialties)
      were more likely to have chosen alternate careers in engineering, research,
      science, business, law, and architecture. CONCLUSIONS: The alternate career
      choices of medical students may be related to their subsequent choice of medical
      specialty.

PMID- 8288073
TI  - [Hepatogastroenteric aspects of tuberculosis in 1993].

PMID- 8288074
TI  - [Treatment of icterus caused by tumoral obstruction of the distal common bile
      duct].

PMID- 8288075
TI  - Relationship between gastric mucosal changes and hemodynamic patterns in
      alcoholic cirrhosis. A prospective study.
AB  - Most gastric mucosal changes in cirrhosis are thought to be related to
      vasculopathy. The aim of this study was to determine whether there was a
      relationship between gastric mucosal changes and hemodynamic in cirrhosis. Thirty
      patients with alcoholic cirrhosis were divided into four groups: no congestive
      gastropathy (n = 6), mild congestive gastropathy type 1 (discrete mosaic pattern)
      (n = 9), mild congestive gastropathy type 2 (obvious mosaic pattern) (n = 9), and
      severe congestive gastropathy (n = 6). The four groups did not significantly
      differ with respect to clinical and biochemical data, degree of hepatic
      dysfunction, or endoscopic signs of portal hypertension. A hyperdynamic
      circulatory syndrome was observed in most patients, but tended to be more
      pronounced in patients with severe congestive gastropathy and mild congestive
      gastropathy type 2 as compared to patients with normal mucosa, or mild congestive
      gastropathy type 1. Systemic vascular resistance was found to be significantly
      lower in high-grade patients (mild congestive gastropathy type 2 + severe
      congestive gastropathy, n = 15) as compared with low-grade patients (no
      congestive gastropathy + mild congestive gastropathy type 1, n = 15) (736 +/- 267
      vs 1,046 +/- 403 dyne.s.cm-5, P = 0.02). Neither splanchnic hemodynamics as
      assessed by the degree of portal hypertension (hepatic venous pressure gradient)
      and superior mesenteric artery vascular resistance (Doppler measurement of the
      pulsatility index) catecholamines or glucagon serum levels differed significantly
      between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288076
TI  - [The role of embolization and chemo-embolization in the emergency treatment of
      hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma].
AB  - Twelve caucasian patients with intraperitoneal hemorrhage due to spontaneous
      rupture of hepatocellular carcinoma were treated by emergency transcatheter
      arterial embolization (n = 9) or chemoembolization (n = 3). Pretreatment
      angiography showed active bleeding (extravasation of contrast medium) in two
      patients only. Successful hemostasis was initially achieved in all patients.
      Early recurrence of hemorrhage was noted in 3 patients with large tumors; two
      were successfully treated by a second embolization and one died immediately after
      the first embolization. Of the 12 patients, two underwent subsequent
      chemoembolization while two had surgical resection of their tumors. The mean
      length of survival was 7 months from the time of rupture. No serious
      complications related to embolization or chemoembolization were noted. Our data
      suggest that emergency embolization or chemoembolization is an effective
      treatment in caucasian patients with intraperitoneal hemorrhage from
      hepatocellular carcinoma. Prognosis of ruptured hepatocellular carcinoma in those
      patients, however, remains poor.

PMID- 8288077
TI  - [Computed tomography during portography. Techniques, indications, results and
      perspectives].

PMID- 8288078
TI  - [Screening of colon cancer: role of genetics].

PMID- 8288079
TI  - [Antro-pyloro-bulbar contractibility in diabetics studied by cineradiography.
      Effect of erythromycin].
AB  - We studied antropyloroduodenal contractility in diabetics and the effect of
      erythromycin IV (100-500 mg) using the non invasive Boiron cineradiographic
      method analysis. Fourteen diabetics and 22 controls were examined. Four hours
      after a standard liquid-solid meal, patients drank 250 mL baryum solution.
      Fluorographic plates (10 x 10 cm) were taken every 2 s during 30 s. Semi
      automatic data processing analysis allowed to measure motility parameters
      including antral (CA) and bulbar (CB) contractility indexes; pyloric opening
      index (OP), gastric (FG) and bulbar (FB) frequencies. Three types of pylorus
      behaviour patterns were define: A and B related to antropyloric and
      antropyloroduodenal coordination respectively and N without coordination. In
      diabetics, CA, OP and FG were decreased vs controls (P < 0.01) (CA: 65.5 +/- 6.8
      vs 83.1 +/- 2.4%; OP: 60.9 +/- 8.7 vs 84.8 +/- 1.9%; FG: 2.42 +/- 0.14 vs 3.08 +/
      0.04 c/min) and antropylorbulbar coordination altered (N was predominant; no
      bulbar cycles at 3/min). Antral hypocontractility was correlated with autonomic
      neuropathy. After erythromycin, radiological parameters returned to normal values
      (CA = 83.0 +/- 2.4%; OP = 86.0 +/- 4.7%; FG = 3.0 +/- 0.16 c/min) and
      coordination improved type N disappeared and FB = 3 c/min (58%). Cineradiographic
      analysis is simple, able to show antropylorobulbar contractile abnormalities, to
      study pharmacological effects, and in diabetics is capable of studying
      improvement of motility parameters with erythromycin.

PMID- 8288080
TI  - [Decrease of fecal beta-galactosidase activity in Crohn disease].
AB  - An increased degradation of colonic mucus by bacterial enzymes might participate
      in the development of mucosal lesions in inflammatory bowel disease. The
      biodisponibility of drugs used in the treatment of such disease relies upon the
      metabolic activity of colonic bacterial flora. This activity can be indirectly
      assessed by measuring fecal enzymatic activities. The aim of this study was to
      compare fecal beta-galactosidase (beta-gal) activity in controls, in patients
      suffering from extradigestive inflammatory disease and in patients with Crohn's
      disease (CD). Three groups were studied including 11 healthy volunteers (6 F, 5
      M) mean age 29 years (21-37), 20 patients with rheumatoid arthritis (RA) (17 F, 3
      M), mean age 61.5 years, and 34 patients with non operated CD (21 F, 13 M) mean
      age: 27 years (13-50). The Crohn disease activity index (CDAI) was > 150 in 24
      and < 150 in 10. beta-gal activity was measured in fecal extracts by its ability
      to hydrolyze paranitrophenyl beta-D-galactopyranoside and expressed as units of
      enzymatic activity/gram of fecal proteins. beta-gal activity was significantly
      decreased in patients with CD (16 +/- 4.5 U/g) (m +/- sem) as compared with
      patients with RA (353 +/- 64 U/g) (P < 0.0001) and to controls (263 +/- 40 U/g)
      (P = 0.002). beta-gal activity was not significantly different in controls and in
      patients with RA. Patients with active CD had a significantly lower beta-gal
      activity than patients with quiescent CD (9.5 +/- 3.7 U/g vs 31.4 +/- 11.5 U/g)
      (P = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288081
TI  - [Total colectomy and ileorectal anastomosis in Crohn's colitis. Functional
      results and recurrence factors (83 cases)].
AB  - Eighty-three consecutive patients (38 men, 45 women) underwent colectomy and
      ileorectal anastomosis (IRA) for Crohn's colitis between 1960 and 1988. The mean
      age at the time of IRA was 28.5 years after a mean interval of four years from
      diagnosis. At the time of IRA, 31 patients had proctitis, while 25 had perianal
      disease. Two patients died postoperatively. Postoperative complications appeared
      in 21 cases (25.3%) including 7 anastomotic leaks (13.2%). Leakage did not imply
      IRA compromise and the diverting ileostomy did not decrease the risk of
      preservation of the ileorectal anastomosis. With a mean follow-up of 8 years
      after IRA, among the 81 surviving patients, it was necessary to retain the stomy
      in five, 24 required exclusion or excision of their IRA (10 defunctioning
      ileostomies, 14 proctectomies) and 52 still had a functioning IRA at follow-up
      (64.2%). Among the 43 recurrences (53%), 21 underwent reoperation. The mean
      interval between IRA and recurrence was 2.2 years. The cumulative rate of
      recurrence reached 47% at 5 years and 57% at 10 years. Fifty percent of the
      patients still had a functioning IRA and were satisfied. Preoperative ileal
      lesions affected the functional results of the IRA and the recurrence rate.
      Development of ileal, rectal or anal disease after IRA significantly increased
      the risk of exclusion of the rectum but did not require suppression of anal
      function. Patients under 30 years of age or patients suffering for more than 5
      years had poorer functional results and more frequent reoperations at 5 years.
      Rectal preservation after IRA may be proposed with success to patients with a
      healthy rectum or with minimal or moderate proctitis, even if there is perianal
      disease that could be safely treated before IRA. In this last setting, the
      patient has to be informed of the risk of rectal preservation and the possible
      risk of requiring ulterior proctectomy.

PMID- 8288082
TI  - [Genetic heterogeneity of certain sporadic colorectal cancers].
AB  - Intratumoral heterogeneity provides information concerning the timing of genetic
      events which occur during colorectal carcinogenesis. In a series of 14 colorectal
      adenocarcinomas, the following genetic alterations were characterized: loss of
      heterozygosity on chromosomes 17 p, 1 p, 18 q, 5 q and 22 q, point mutations on
      TP53 and K-RAS genes, change in DNA index. Six of the 14 initial samples were
      investigated for putative genetic heterogeneity. In two cases, variations in
      genetic alterations on chromosome 17 p and gene TP53 were demonstrated. These
      events seem to occur at a late stage in colorectal carcinogenesis.

PMID- 8288083
TI  - [Resurgence of a forgotten pathology: pylephlebitis caused by tuberculous
      adenopathies].
AB  - The incidence of abdominal tuberculosis represents less than 1% of all forms of
      tuberculosis. We report the case of a portal vein thrombosis associated with
      tuberculous adenopathy of the hepatic hilum discovered in a young woman free of
      symptoms, without any risk factors, who had recovered from a cavity pulmonary
      tuberculosis after a classical anti-tuberculous treatment. This case suggests
      that abdominal tuberculosis often remains undiagnosed. Reemergence of
      tuberculosis is likely because of the increase in the incidence of the acquired
      immunodeficiency syndrome.

PMID- 8288084
TI  - [Single-stage resection of at least 6 liver segments in cases of liver tumors].
AB  - Seven partial liver resections of at least six hepatic segments (five extended
      left hepatectomies, also called left trisegmentectomies, and two subtotal
      hepatectomies) were performed for tumor (of malignant nature in 6 cases). Six of
      seven patients were admitted for liver transplantation and one for liver
      resection. These procedures were performed under total vascular exclusion of the
      liver in six cases (with a veno-venous bypass in two cases) and with the Pringle
      maneuver in one case. Postoperative liver function was satisfactory in six cases
      whereas one patient died of hepatic failure on the tenth postoperative day. There
      was one bile duct stricture at eight months, after extended left hepatectomy.
      Four patients survived more than one year, three with hepatic tumor recurrence
      and one with distant metastases. Two patients were still alive, one after
      fourteen months with tumor recurrence in the liver, the other after seventeen
      months. In selected cases, partial hepatic resection of more than six segments
      can be performed for very large tumors. In cases of malignant tumors, a short
      period of survival with good quality of life can be offered to these patients.

PMID- 8288085
TI  - [Abdominal paraesophageal bronchogenic cyst].
AB  - We report a case of abdominal paraesophageal bronchogenic cyst in a 19 year-old
      patient who complained of dysphagia. Based on this exceptional finding, the
      authors state overview the pathogenic theories and the histologic features which
      distinguish para-esophageal bronchogenic cysts from duplications. Preoperative
      diagnosis is difficult, but endoscopic ultrasound seems to be the imaging method
      of choice.

PMID- 8288086
TI  - [Asthma and bronchospasm during preparation for colonoscopy with an aromatized
      solution of polyethylene glycol].

PMID- 8288087
TI  - [Hepatitis C after retrograde cholangiography].

PMID- 8288088
TI  - [Eruptive mucocutaneous lichen planus during treatment of chronic hepatitis C
      with interferon alpha].

PMID- 8288089
TI  - [Peritoneal tuberculosis masked by fluoroquinolones in a patient with liver
      cirrhosis].

PMID- 8288090
TI  - [Icterus caused by tuberculous adenopathies].

PMID- 8288091
TI  - [Ultrasonic endoscopy in the diagnosis of an abnormality of the biliopancreatic
      junction associated with tumor of the gallbladder].

PMID- 8288092
TI  - [Hepatic involvement in systemic mastocytosis].

PMID- 8288093
TI  - [Acute hepatic involvement during ingestion of acitretin].

PMID- 8288094
TI  - [Cytolytic hepatic involvement after administration of cetirizine (Zyrtec)].

PMID- 8288095
TI  - [Curietherapy at high dose radiation in the treatment of cancer of the
      esophagus].

PMID- 8288096
TI  - [Treatment with laser Nd YAG of digestive angiodysplasias in dialysed patients
      with chronic kidney failure].

PMID- 8288097
TI  - [Prevalence of occult digestive hemorrhages during heavy-endurance exercise].

PMID- 8288098
TI  - [Acute hemorrhagic colitis caused by pristinamycin: two cases with association of
      Klebsiella oxytoca and Clostridium difficile].

PMID- 8288099
TI  - [Can adjuvant chemotherapy of hepatocellular carcinoma improve results of liver
      transplantation?].

PMID- 8288100
TI  - DNA probes for identification of the ectomycorrhizal fungus Tuber magnatum Pico.
AB  - The random amplified polymorphic DNA (RAPD) technique was used to develop DNA
      probes for the identification of ectomycorrhizal fungi belonging to the genus
      Tuber. RAPD fingerprinting revealed a high degree of interspecific variability
      and a low degree of intraspecific variability. One band (approximately 1.5 kb),
      consistently appearing when genomic DNA was amplified with an aspecific primer
      (OPA-18), was found to be a good marker for Tuber magnatum, and was used as a
      probe in Southern hybridization experiments. The specificity of the results
      suggests that this probe may be useful in developing specific primers for PCR
      amplifications.

PMID- 8288101
TI  - Membrane fatty acid analysis of Antarctic bacteria.
AB  - Randomly selected strains of a bacterial collection of marine sea-ice bacteria
      from Antarctica were analyzed to obtain a profile of the membrane fatty acids.
      Results showed that short chain saturated and unsaturated fatty acids were more
      common in the psychrotrophs when compared to psychrophiles. In contrast, branched
      chain fatty acids were more abundant in the psychrophiles.

PMID- 8288102
TI  - Analysis of the Salmonella fim gene cluster: identification of a new gene (fimI)
      encoding a fimbrin-like protein and located downstream from the fimA gene.
AB  - The fimA gene coding for the major component (fimbrin) of type 1 fimbriae was
      mapped within the Salmonella typhi fim gene cluster, and its nucleotide sequence
      determined. The deduced amino acid sequence of S. typhi fimbrin is highly
      homologous to that of S. typhimurium type 1 fimbrin and showed similarity to that
      of other enterobacterial type 1 fimbrins. Downstream of fimA, an open reading
      frame was found, named fimI, able to encode a fimbrin-like protein. The fimI
      product could represent the counterpart, in type 1 fimbriae, of the PapH protein
      involved in cell anchoring and length modulation of Escherichia coli Pap pili.
      This genetic organization was found to be common to other Salmonella serovars,
      including S. typhimurium and S. choleraesuis.

PMID- 8288103
TI  - Hemolytic toxin produced by Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis no. 381 and ATCC 33277 produced an extracellular
      hemolytic toxin which was heat-labile, trypsin-sensitive, and lytic to human,
      horse, sheep and rabbit erythrocytes. The hemolytic toxin is a 'hot-cold', thiol
      independent toxin. The production of the hemolytic toxin was greatly enhanced by
      addition of hemoglobin to the culture medium.

PMID- 8288104
TI  - Differences in sensitivity to NADH of purified pyruvate dehydrogenase complexes
      of Enterococcus faecalis, Lactococcus lactis, Azotobacter vinelandii and
      Escherichia coli: implications for their activity in vivo.
AB  - The effect of NADH on the activity of the purified pyruvate dehydrogenase
      complexes (PDHc) of Enterococcus (Ec.) faecalis, Lactococcus lactis, Azotobacter
      vinelandii and Escherichia coli was determined in vitro. It was found that the
      PDHc of E. coli and L. lactis was active only at relatively low NADH/NAD ratios,
      whereas the PDHc of Ec. faecalis was inhibited only at high NADH/NAD ratios. The
      PDHc of Azotobacter vinelandii showed an intermediate sensitivity. The organisms
      were grown in chemostat culture under conditions that led to different
      intracellular NADH/NAD ratios and the PDHc activities in vivo could be calculated
      from the specific rates of product formation. Under anaerobic growth conditions,
      only Ec. faecalis expressed PDHc activity in vivo. The activities in vivo of the
      complexes of the different organisms were in good agreement with their properties
      determined in vitro. The physiological consequences of these results are
      discussed.

PMID- 8288105
TI  - Evidence for the presence of a receptor for the cytolethal distending toxin
      (CLDT) of Campylobacter jejuni on CHO and HeLa cell membranes and development of
      a receptor-based enzyme-linked immunosorbent assay for detection of CLDT.
AB  - Using ligand blotting, it was found that partially purified cytolethal distending
      toxin prepared from an enterotoxigenic strain of Campylobacter jejuni, bound to
      two peptides of molecular masses of approximately 59 kDa and 45 kDa and to a
      single peptide of 59 kDa in protein blots prepared from HeLa and CHO cell
      membranes, respectively. In contrast, labile toxin of Escherichia coli and
      cholera toxin bound to a single peptide of the same molecular mass (15 kDa) on
      protein blots prepared from both CHO and HeLa cell crude membranes resolved by
      gel electrophoresis. This banding pattern was identical using SDS-solubilized
      membrane, with or without heat treatment, but no band was obtained when reduced
      (treatment with 2-mercaptoethanol) samples were used for the gel electrophoresis.
      The differences between receptors of cytolethal distending toxin and cholera
      toxin/labile toxin were exploited to develop a receptor-based enzyme-linked
      immunosorbent assay for detection of cytolethal distending toxin which involved
      the consecutive addition of either solubilized CHO or HeLa membranes, antigen and
      antibody. This enzyme-linked immunosorbent assay consistently detected crude
      cytolethal distending toxin diluted up to 16-fold. The receptor-based enzyme
      linked immunosorbent assay for detection of cytolethal distending toxin developed
      in this study is a suitable alternative assay which can be performed easily in
      laboratories with minimal facilities and, more importantly, the results are
      available within a few hours as compared to times of up to 5 days in the
      conventional tissue culture detection of cytolethal distending toxin.

PMID- 8288106
TI  - UDP-sugar hydrolase isozymes in Salmonella enterica and Escherichia coli: silent
      alleles of ushA in related strains of group I Salmonella isolates, and of ushB in
      wild-type and K12 strains of E. coli, indicate recent and early silencing events,
      respectively.
AB  - Escherichia coli contains a single periplasmic UDP-glucose hydrolase (5'
      nucleotidase) encoded by ushA. Salmonella enterica, serotype Typhimurium, also
      contains a single UDP-glucose hydrolase but, in contrast to E. coli, it is
      membrane-bound and is encoded by the non-homologous ushB gene; Salmonella
      enterica (Typhimurium) also contains a silent allele of the ushA gene (ushA0). In
      this report, we show that nearly all natural isolates of Salmonella contain both
      UDP-sugar hydrolases, i.e. they are UshA+ UshB+. The only exceptions are all from
      sub-group I (S. gallinarum, S. pullorum, and most Typhimurium strains), are UshA-
      UshB+, and several have been shown to contain an ushA0 allele. These data,
      together with the fact that these latter strains are closely related genetically,
      strongly suggests a recent silencing mutation(s). We also report the presence in
      E. coli K-12, and in natural isolates of E. coli, of a DNA sequence which is
      homologous to the ushB gene of Salmonella; since E. coli does not contain UshB
      activity, we tentatively refer to this sequence as ushB0. Since all E. coli
      strains investigated are UshB-, we conclude that the silencing mutation(s)
      occurred relatively early following the divergence of Escherichia coli and
      Salmonella from a common ancestor that was ushA+ ushB+.

PMID- 8288107
TI  - Membrane localisation of a UDP-sugar hydrolase, in Salmonella, is by an uncleaved
      N-terminal signal peptide.
AB  - Most isolates of Salmonella contain two unrelated UDP-sugar hydrolases, one of
      which, encoded by the ushB gene, is inner membrane-associated. Previous studies
      showed that this enzyme contains a typical N-terminal signal peptide; the
      evidence also indicated, however, that this peptide is not cleaved, and serves to
      anchor the UshB protein in the inner membrane. In this report, we present strong
      evidence that this is indeed the case by using ushB'-'blaM fusions to demonstrate
      that this signal peptide is capable of localising beta-lactamase to the inner
      membrane. We also present evidence that UshB is located on the exterior
      (periplasmic) side of the membrane, and hence has an 'N-terminus inside/C
      terminus outside' membrane orientation, consistent with a role in the degradation
      of external substrates.

PMID- 8288108
TI  - Further studies of 31 temperature-sensitive mutants of mouse cytomegalovirus:
      thermal stability, replication and analysis of temperature-sensitive functions by
      temperature shift.
AB  - A study of 31 temperature-sensitive mutants of mouse cytomegalovirus has
      indicated that two mutants (tsm1, tsm31) may be defective in immediate
      early/early functions, two (tsm2, tsm3) may be defective in early functions and
      six (tsm9, tsm18, tsm22, tsm23, tsm28, tsm30) may be defective in early/late
      functions while the remainder are late function-defective mutants as determined
      by temperature-shift experiments. Three mutants (tsm1, tsm2, tsm3) were more
      thermostable than wild-type virus while three (tsm16, tsm26, tsm28) were more
      thermolabile; the remainder were similar in their thermostability to wild-type
      virus.

PMID- 8288109
TI  - Development of an in vitro model of Toxoplasma gondii cyst formation.
AB  - Toxoplasma gondii tissue cyst reactivation is a major pathogenic mechanism in
      ocular toxoplasmosis, disease associated with AIDS and organ transplantation. The
      mechanisms associated with cyst formation and reactivation have not been
      elucidated. The complexity of studying these issues in animal models has led to
      the development of in vitro tissue culture strategies for cyst formation. In the
      present study we have adopted the human embryonic lung fibroblast (HEL) as the
      host cell and have compared the cyst forming abilities of eight clinical
      isolates. We describe by transmission electron microscopy and quantitative light
      microscopy the development of cysts in vitro. The numbers of in vitro cysts
      increased with time for all isolates. Cyst cultures were stabilised by
      manipulation of the free parasite load, an observation not previously recorded.
      Thus, in this paper we describe a viable model for the analysis of the mechanisms
      of Toxoplasma cyst development.

PMID- 8288110
TI  - Yeast genes involved in growth inhibition by Pseudomonas syringae pv. syringae
      syringomycin family lipodepsipeptides.
AB  - Saccharomyces cerevisiae genes encoding functions necessary for inhibition by the
      Pseudomonas syringae pv. syringae cyclic lipodepsipeptide, syringomycin-E, were
      identified by mutant analyses. Syringomycin-E-resistant mutants were isolated,
      shown to contain single recessive mutations, and divided into eight gene
      complementation groups. Representative strains from five groups were resistant to
      nystatin, and deficient in the plasma membrane lipid, ergosterol. All of the
      mutant strains were resistant to the related cyclic lipodepsipeptides,
      syringotoxin and syringostatin. The findings show that: 1) at least eight gene
      encoded functions participate in the inhibitory response to syringomycin; 2)
      ergosterol is important for this response; 3) the three related lipodepsipeptides
      have similar modes of action.

PMID- 8288111
TI  - Transposon mutagenesis of Clostridium acetobutylicum P262: isolation and
      characterization of solvent deficient and metronidazole resistant mutants.
AB  - An efficient transposon mutagenesis system using conjugative transposons Tn916
      and Tn925::Tn917 was established for Clostridium acetobutylicum P262, an
      industrial strain which has proved difficult to manipulate genetically.
      Transposon insertions occurred at several different locations to produce a
      variety of mutants. An oligosporogenous mutant deficient in acetone and butanol
      production, and two sporulation-deficient and metronidazole resistant mutants
      were characterized with respect to differentiation and solvent production.
      Tn925::Tn917 inserted near a string of adenosine residues and transposon
      insertion was often multiple.

PMID- 8288112
TI  - Complementation of growth defect in an ampC deletion mutant of Escherichia coli.
AB  - beta-Lactamase genes of class-A (Rtem) and class-C (ampC) were placed under
      control of an inducible tac-promoter and expressed in Escherichia coli.
      Expression of RTEM had no observable effect on the growth properties of E. coli
      strains HB101 (ampC+) or MI1443 (delta ampC). E. coli MI1443 exhibited a decline
      in growth rate at mid-exponential phase which could be delayed by expression of
      AmpC at early-exponential phase. AmpC expression otherwise inhibited growth,
      particularly during the transition into exponential phase where growth was
      prevented altogether. We suggest that the AmpC beta-lactamase, but not RTEM, may
      have an additional cellular function as a peptidoglycan hydrolase.

PMID- 8288113
TI  - Circumstances surrounding deaths from asthma in Cook County (Chicago) Illinois.
AB  - The death rate from asthma has been increasing in the U.S. and in many other
      countries and is considered unacceptably high. There is little information as to
      circumstances surrounding these fatalities that would lead to effective
      interventions to prevent deaths. In this study, cases of asthma deaths from the
      Office of the Medical Examiner in Cook County, (Chicago), Illinois were
      identified in subjects 45 years of age or less who died from asthma. We reviewed
      clinical information surrounding the deaths, contacted surviving kin, friends, or
      informants, and reviewed autopsy findings and toxicologic results. Deaths were
      classified as (1) from asthma, (2) probably from asthma, (3) of indeterminate
      cause, and (4) coincidental to but not from asthma. From 39 cases from one
      pathologist's cases of asthma deaths during 1985-1992, deaths were from or
      probably from asthma in 22/39 (56.4%) of cases. Eight (20.5%) cases were
      classified as indeterminate because of a positive or unknown asthma prodrome but
      in which toxicologic results were positive. Nine (23.1%) cases were classified as
      death coincidental to but not from asthma because of the absence of a prodrome of
      increased symptoms associated with positive toxicologic results. Overall from 23
      cases where some toxicologic testing was performed, 14 (60.8%) were positive,
      individually or in combination, for cocaine, benzoylecgonine (cocaine
      metabolite), codeine, phencyclidine (animal tranquilizer), morphine, methadone,
      and ethanol (> 0.8 g/L). Out-of-hospital asthma deaths in 39 subjects were
      complicated by a high incidence of illicit drug use, lack of identifiable
      managing physicians, lack of antiinflammatory medications, and in some cases not
      having been examined by a physician in the past year.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8288114
TI  - Sudden asphyxic asthma following exposure to high concentrations of
      dermatophagoides group I allergen.

PMID- 8288115
TI  - Malignant potentially fatal asthma: achievement of remission and the application
      of an asthma severity index.
AB  - Patients fulfilling diagnostic criteria for malignant potentially fatal asthma
      require aggressive involvement by the physician to prevent avoidable fatalities
      from asthma. Efforts to overcome barriers to treatment caused by noncompliance
      are critical to successful care. This report reviews five patients with malignant
      potentially fatal asthma in remission, in whom noncompliance played the major
      role in preventing control of asthma. Through patient confrontation and the
      monitoring of serum concentrations of prednisone and its metabolite prednisolone,
      noncompliance may be addressed. Psychiatric referral may also be of benefit, if
      accepted by the patient and family. Use of injectable methylprednisolone may be a
      necessary alternative to prevent life-threatening complications of asthma. In all
      patients, keeping medical regimens as simple as possible is advocated, with the
      use of the lowest doses of medication necessary to maintain the control of
      symptoms, and the prevention of morbidity and mortality. An asthma severity index
      for the illustration of longitudinal disease severity is applied to these
      patients.

PMID- 8288116
TI  - Osteoporosis in corticosteroid-treated asthmatic patients: clinical correlates.
AB  - This study sought to identify clinical and laboratory characteristics associated
      with the development of osteoporosis in 44 corticosteroid (CS)-treated asthmatic
      patients. Percentage predicted bone density was inversely correlated with both
      the duration of CS therapy (r = -.39, p = 0.009) and 24-hour urine calcium
      excretion (chi 2 = 5.2, p = 0.022). Bone density was not related to prednisone
      equivalent dose, alternate day versus daily therapy or serum cortisol levels.
      These data suggest that (1) long duration of CS therapy and increased urine
      calcium may identify patients at increased risk of developing CS-induced
      osteoporosis, and (2) urinary loss of calcium may be of particular importance in
      the pathogenesis of this condition.

PMID- 8288117
TI  - Systemic reactions to immunotherapy.
AB  - Systemic anaphylactic reactions occur in a small percentage of patients receiving
      allergen immunotherapy. A 1 year study was performed in a large health
      maintenance organization to determine the incidence of systemic reactions (SR) to
      allergen immunotherapy. We measured the number of SR that occurred during a 12
      months period. A SR data sheet was completed for each reaction, documenting the
      time of onset, symptoms, treatment, history of asthma or previous reaction, and
      concentration and type of extract. Twenty-seven thousand eight hundred six
      injection visits resulted in 143 SR (0.51%). Forty-five percent of the patients
      (pts) with SR had a history of prior SR, 50% had a history of asthma, and 36%
      developed reactions in season. Seventy-two percent of SR started within 30
      minutes, although 8% appeared after 2 hours. Fifty-seven percent of SR occurred
      at concentrations of 1,000-10,000 PNU/cc, 25% at 10-100 PNU/cc, and 17% when both
      concentrations were given at the same visit. Eighty-three percent of SR were
      judged to be mild, nonlife threatening reactions, requiring no treatment or
      antihistamine therapy only. Seventeen percent were judged to be more severe,
      requiring treatment with epinephrine, with or without other agents. SR are a
      small but definite risk of immunotherapy. Most SR are mild, but some may be life
      threatening. The majority of reactions occur within 30 minutes, but significant
      reactions may occur after 2 hours. A large percentage of SR occurred in patients
      with a history of asthma, previous SR, or both.

PMID- 8288118
TI  - The relationship between plasma thrombospondin level and the clinical course of
      atopic dermatitis.
AB  - The tests currently used to monitor atopic dermatitis in children--serum IgE
      level and eosinophil count--are not sensitive enough to accurately track the
      course of the disease. Because previous studies have shown that atopic dermatitis
      is an inflammatory disease and because our previous work has shown that plasma
      thrombospondin level correlates well with the course of other inflammatory
      diseases, we conducted this study to determine the relationship between plasma
      thrombospondin level and the severity of skin inflammation in children with
      atopic dermatitis. Eosinophil count, serum IgE level, and plasma thrombospondin
      level were measured in 48 children with atopic dermatitis at onset of flare-up, 2
      weeks after treatment started, and 2 months after treatment started. The results
      of all three tests were better after 2 months of therapy than they had been at
      the initial visit, but only plasma thrombospondin level showed a statistically
      significant decrease, which coincided with clinical improvement. Plasma
      thrombospondin level seems to correlate with the clinical course of patients with
      atopic dermatitis better than do serum IgE level or eosinophil count.

PMID- 8288119
TI  - Osteoporosis, cytokines, and glucocorticoids.

PMID- 8288120
TI  - Idiopathic anaphylaxis (IA): suggested theories relative to the pathogenesis and
      response to therapy.

PMID- 8288121
TI  - Platelets, thrombospondin, and atopic dermatitis.

PMID- 8288122
TI  - Anaphylaxie et idiosyncrasie. 1992 [Anaphylaxis and idiosyncrasy. 1992].

PMID- 8288123
TI  - bHLH factors in muscle development: dead lines and commitments, what to leave in
      and what to leave out.

PMID- 8288124
TI  - odd-paired: a zinc finger pair-rule protein required for the timely activation of
      engrailed and wingless in Drosophila embryos.
AB  - The pair-rule gene, odd-paired (opa), is essential for parasegmental subdivision
      of the Drosophila embryo. In addition to its previously defined role in the
      activation of wingless (wg) in odd parasegments, we find that opa is required for
      the timely activation of wg in the remaining parasegments and for the timely
      activation of engrailed (en) in all parasegments. opa encodes a zinc finger
      protein with fingers homologous to those of the Drosophila segment polarity gene
      ciD, the human glioblastoma gene GLI and the Caenorhabditis elegans sex
      determination gene tra-1. Previous work showed that opa activity was essential
      for the establishment of alternate parasegments, suggesting opa expression or
      activity would be spatially restricted like other pair-rule genes. Instead, opa
      mRNA and protein are found throughout all segment primordia. Thus, opa does not
      act in a spatially restricted manner to establish the position of en and wg
      expression. Rather, opa must cooperate with other spatially restricted proteins
      to achieve proper subdivision of the Drosophila embryo.

PMID- 8288125
TI  - The Drosophila segment polarity gene dishevelled encodes a novel protein required
      for response to the wingless signal.
AB  - The Drosophila Wnt-1 homolog, wingless (wg), is involved in the signaling of
      patterning information in several contexts. In the embryonic epidermis, Wg
      protein is secreted and taken up by neighboring cells, in which it is required
      for maintenance of engrailed transcription and accumulation of Armadillo protein.
      The dishevelled (dsh) gene mediates these signaling events as well as wg
      dependent induction across tissue layers in the embryonic midgut. dsh is also
      required for the development processes in which wg functions in adult
      development. Overall, cells lacking dsh are unable to adopt fates specified by
      Wg. dsh functions cell autonomously, indicating that it is involved in the
      response of target cells to the Wg signal. dsh is expressed uniformly in the
      embryo and encodes a novel protein with no known catalytic motifs, although it
      shares a domain of homology with several junction-associated proteins. Our
      results demonstrate that dsh encodes a specific component of Wg signaling and
      illustrate that Wnt proteins may utilize a novel mechanism of extracellular
      signal transduction.

PMID- 8288126
TI  - A functional Ets DNA-binding domain is required to maintain multipotency of
      hematopoietic progenitors transformed by Myb-Ets.
AB  - Earlier work demonstrated that the Myb-Ets fusion protein of E26 avian leukemia
      virus induces the proliferation of multipotent hematopoietic progenitors (MEPs).
      These progenitors differentiate spontaneously at low frequencies along the
      erythroid lineage, and following the introduction of kinase/ras-type oncogenes or
      treatment with TPA, they are induced to differentiate along the myelomonocytic
      and eosinophilic lineages. Here, we show that the ts1.1 mutant of E26 encodes an
      Ets DNA-binding domain that is both defective and thermolabile for binding of
      specific DNA sequences. Correlating with this, ts1.1 MEP colonies transformed at
      the permissive temperature exhibit elevated levels of erythroid cells and
      eosinophils, whereas at the nonpermissive temperature they are induced to
      differentiate along the erythroid and myelomonocytic lineages and, to a lesser
      extent, along the eosinophil lineage. Induction of the former two lineages cannot
      be separated by pulse shift experiments and is essentially completed 2.5 days
      after temperature shift. Our results indicate that the Ets portion of the Myb-Ets
      fusion protein inhibits the lineage commitment of multipotent hematopoietic
      progenitors, probably via binding to regulatory DNA sequences of specific target
      genes.

PMID- 8288127
TI  - A novel POU domain gene, zebrafish pou2: expression and roles of two
      alternatively spliced twin products in early development.
AB  - POU domain proteins are a large family of transcriptional regulatory proteins,
      many of which are implicated in the control of gene expression during early
      development. We describe here the cloning and expression of zebrafish pou2, a
      novel POU domain gene related to the mouse germ-line-specific transcription
      factor oct-3. Zebrafish pou2 is maternally expressed, and the transcripts are
      present from the one-cell stage to the gastrula stage. In situ hybridization
      analyses revealed that the transcripts were present in all blastomeres until the
      midblastula stage and that the expression was restricted to the epiblast during
      gastrulation. We found that alternatively spliced transcripts, t-pou2 RNAs, were
      also expressed in the embryos. In contrast to the Pou2 product, the t-Pou2
      product lacks DNA-binding activity because of its incomplete POU domain
      structure. To examine the roles of the Pou2 and t-Pou2 products, we increased
      their expression in the embryo by microinjection of synthetic pou2 and t-pou2
      RNAs into the fertilized eggs at the one-cell stage. Most embryos that developed
      from the eggs injected with pou2 RNA did not show any obvious developmental
      defects. In contrast, overexpression of the t-Pou2 product greatly affected the
      embryonic development: There was strong developmental retardation or arrest due
      to the incomplete gastrulation. In the affected embryos, expression of zebrafish
      T gene was reduced and the hypoblast formation was disturbed. Temporal and
      spatial expression patterns and the effects of overexpression of these products
      on development are consistent with the idea that the Pou2 and t-Pou2 proteins are
      involved in early development of zebrafish embryos. They may be involved in the
      proliferation of blastomeres in undetermined state at the blastula stage and/or
      the early cell commitment events at the gastrula stage. Also, our results
      indicate that different products generated as a result of alternative splicing
      from the same gene possess distinct functional capacities.

PMID- 8288128
TI  - unc-101, a gene required for many aspects of Caenorhabditis elegans development
      and behavior, encodes a clathrin-associated protein.
AB  - Our genetic analysis indicates that the unc-101 gene of Caenorhabditis elegans is
      required for many aspects of development and behavior, including negative
      regulation of vulval differentiation. We have cloned unc-101 and found that it
      encodes a homolog of the mammalian medium chains of clathrin-associated protein
      complexes located at the trans-Golgi and the plasma membrane, AP47 and AP50,
      respectively. Therefore, clathrin-mediated events might contribute to the
      negative regulation of vulval differentiation. Comparison of sequences, including
      a full-length sequence of a C. elegans AP50 homolog, reveals that UNC-101 is most
      closely related to AP47. Mouse AP47 and nematode UNC-101 proteins are
      functionally equivalent as assayed in transgenic nematodes. We have sequenced the
      mutant alleles of unc-101 identified in various genetic screens and shown that
      all but one are deletions or nonsense mutations, suggesting that these alleles
      severely reduce unc-101 function.

PMID- 8288129
TI  - Anabaena xisF gene encodes a developmentally regulated site-specific recombinase.
AB  - Two DNA elements are excised from the chromosome during Anabaena heterocyst
      differentiation. We have identified the gene xisF which encodes the site-specific
      recombinase responsible for the excision of a 55-kb element from within the fdxN
      gene. The cloned xisF gene is sufficient to cause site-specific rearrangement of
      an artificial substrate in Escherichia coli. Inactivation of xisF in the Anabaena
      chromosome prevents excision of the fdxN element and growth in nitrogen-deficient
      medium but does not alter the development of heterocysts. Forced transcription of
      xisF in vegetative cells did not result in excision of the fdxN element,
      suggesting that other factors may be involved in cell-type specificity. The
      predicted XisF protein shows significant similarity to the Bacillus subtilis
      SpoIVCA recombinase.

PMID- 8288130
TI  - A weak germ-line excision mutation blocks developmentally controlled
      amplification of the rDNA minichromosome of Tetrahymena thermophila.
AB  - During development of the somatic macronucleus of Tetrahymena thermophila, the
      rDNA is excised from its germ-line chromosome, rearranged into a palindrome, and
      amplified to 10(4) copies. We have identified a cis-acting germ-line mutation,
      rmm11/6, that prevents amplification of the rDNA in all but approximately 1 in
      10(5) cells when it is the only rDNA allele in the developing macronucleus. The
      rmm11/6 mutation resides in a conserved element required for excision, the
      chromosome breakage sequence (Cbs) flanking the 3' end of the rDNA. Surprisingly,
      the rmm11/6 mutation only weakly affects excision of the rDNA from its germ-line
      location; at least 25% of cells heterozygous for this mutation correctly excise
      the affected rDNA allele. In heterozygotes, when this rDNA allele is excised, it
      is also poorly amplified. The rDNA amplification defect caused by this mutation
      is not overcome by delaying amplification with the DNA synthesis inhibitor
      aphidicolin, indicating that rDNA excision and amplification are not
      experimentally separable. Our experiments provide the first evidence that the
      capacity to amplify the rDNA is restricted in the developing macronucleus. We
      propose that the rmm11/6 mutation delays excision of the rDNA and that the
      developmental progression of the macronucleus past a restricted window for
      amplification is responsible for the severe amplification defect caused by this
      weak rDNA excision mutation.

PMID- 8288131
TI  - p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and
      contact inhibition to cell cycle arrest.
AB  - Cell-cell contact and TGF-beta can arrest the cell cycle in G1. Mv1Lu mink
      epithelial cells arrested by either mechanism are incapable of assembling active
      complexes containing the G1 cyclin, cyclin E, and its catalytic subunit, Cdk2.
      These growth inhibitory signals block Cdk2 activation by raising the threshold
      level of cyclin E necessary to activate Cdk2. In arrested cells the threshold is
      set higher than physiological cyclin E levels and is determined by an inhibitor
      that binds to cyclin E-Cdk2 complexes. A 27-kD protein that binds to and prevents
      the activation of cyclin E-Cdk2 complexes can be purified from arrested cells but
      not from proliferating cells, using cyclin E-Cdk2 affinity chromatography. p27 is
      present in proliferating cells, but it is sequestered and unavailable to interact
      with cyclin E-Cdk2 complexes. Cyclin D2-Cdk4 complexes bind competitively to and
      down-regulate the activity of p27 and may thereby act in a pathway that reverses
      Cdk2 inhibition and enables G1 progression.

PMID- 8288132
TI  - Acetylated histone H4 on the male X chromosome is associated with dosage
      compensation in Drosophila.
AB  - Dosage compensation in Drosophila occurs by an increase in transcription of genes
      on the X chromosome in males. This elevated expression requires the function of
      at least four loci, known collectively as the male-specific lethal (msl) genes.
      The proteins encoded by two of these genes, maleless (mle) and male-specific
      lethal-1 (msl-1), are found associated with the X chromosome in males, suggesting
      that they act as positive regulators of dosage compensation. A specific
      acetylated isoform of histone H4, H4Ac16, is also detected predominantly on the
      male X chromosome. We have found that MLE and MSL-1 bind to the X chromosome in
      an identical pattern and that the pattern of H4Ac16 on the X is largely
      coincident with that of MLE/MSL-1. We fail to detect H4Ac16 on the X chromosome
      in homozygous msl males, correlating with the lack of dosage compensation in
      these mutants. Conversely, in Sxl mutants, we detect H4Ac16 on the female X
      chromosomes, coincident with an inappropriate increase in X chromosome
      transcription. These data suggest that synthesis or localization of H4Ac16 is
      controlled by the dosage compensation regulatory hierarchy. Dosage compensation
      may involve H4Ac16 function, potentially through interaction with the product of
      the msl genes.

PMID- 8288133
TI  - [Current concepts in the pathogenesis and treatment of abortion and septic shock
      I. The epidemiology, pathogenesis and management of septic abortion].
AB  - In view of the illegal status induced abortion, it is difficult to determine the
      degree to which it is practiced. In our country there are a great inconsistency
      in the statistics on the number of abortions and the number of maternal deaths
      due to this cause. The principal complication of the illegal induced abortion is
      the septic abortion, with an uncontrolled bacterial infection and systemic
      complications that dominate the clinical picture. The mortality of the septic
      abortion is elevated, in the majority of cases due to septic shock. The treatment
      consist on antimicrobial agents and early surgery. A reduction on the number of
      illegal abortions will decrease significantly the number of septic abortion's
      cases.

PMID- 8288134
TI  - [Hepatocellular hemorrhagic necrosis and subcapsular hepatic hematoma in 20 cases
      of hypertension in the third trimester of pregnancy (toxemia)].
AB  - Hepatocellular hemorrhagic necrosis was found in 11 cases, that correspond to 55%
      of 20 cases of death due to hypertensive disease of third trimester of pregnancy:
      eclampsia, in 81.8% was diffuse; in 18.1% it was focal: it was present at 18
      years to 38 years of age; at 25.5 years of age, average; 36.3% were primipara,
      36.3% multiparae. Subcapsular hepatic hematoma was found in five cases, 60% with
      intact capsule, and 40% with broken capsule. From the five cases, 60% were
      multiparae; 80% was developed during the third trimester of pregnancy; 20% during
      the second trimester; 80% showed pain associated with vomiting; 80% evolutionated
      towards eclampsia. These five cases of subcapsular hepatic hematoma, in
      principle, developed a subcapsular hepatic hematoma syndrome; ulteriorly with the
      development of shock, the subcapsular hepatic hematoma syndrome, appeared, with
      capsule rupture. We considered the hepatocellular hemorrhagic necrosis, hepatic
      subcapsular hematoma with intact Glisson capsule, and hepatic hematoma with
      broken capsule, three stages of the same disease.

PMID- 8288135
TI  - [Mesenteric venous thrombosis (MVT) in the puerperium. A report of 2 cases].
AB  - Two cases of mesenteric venous thrombosis (MVT) during puerperium are reported
      and the medical literature about this condition is reviewed. In none of the 65
      articles reviewed was an association of these conditions reported. We believe
      that there are certain hematologic and hormonal conditions in puerperium that may
      explain this association. The current clinical presentation, diagnostic
      modalities and management are presented, and we think that it should be suspected
      in a patient in puerperium with symptoms of acute abdomen.

PMID- 8288136
TI  - [Chlamydia trachomatis infection in the cervix uteri].
AB  - We studied 93 gynecological samples of uterine cervix of patients at Hospital de
      Gineco Obstetricia No. 3, Centro Medico La Raza, IMSS, Health Promotion and
      Family Medicine Unit No. 5 with monoclonal antibodies. We found Chlamydia
      trachomatis in 28.4% in women where the infection was suspected. We should think
      in infection by Chlamydia trachomatis in women with acute cervicitis, acute
      salpingitis, cervical abnormalities, and to run the specific tests for its
      detection.

PMID- 8288137
TI  - [The clinical and lipid metabolic effects of a gestoden- and ethynyl estradiol
      based monophasic contraceptive].
AB  - This is a clinical study to evaluate the efficacy, clinical side effects and in
      lipid metabolism of a new hormonal contraceptive preparation containing 75 mcg.
      of ethinyloestradiol. Thirty Mexican health women in reproductive age were
      studied for 12 months, giving a total of 360 cycles. The medication was highly
      effective for contraception, because pregnancies did not occur in this period.
      The clinical side effects were mild and less frequent that the ones informed with
      the use of other available hormonal oral contraceptives. In lipid metabolism, we
      did not find the adverse effects most frequently observed with the use of
      previous progestagens. This study, like previous ones, concludes that the
      combination of gestodene and ethinylestradiol is highly effective as a
      contraceptive with a low incidence of collateral side effects and due to its lack
      of interference with the metabolism of lipids is particularly suited for cases of
      high risk to develop pathology associated with alterations in lipid metabolism.

PMID- 8288138
TI  - Family stress and resources: potential areas of intervention in children recently
      diagnosed with diabetes.
AB  - This article examines the relationships among family stress, family capabilities,
      and the health status of 53 children diagnosed with insulin-dependent diabetes
      mellitus. Assessments were done at an outpatient diabetes clinic of family
      coping, resources, and stress; disease-related knowledge; metabolic control
      (HbA1); and endogenous insulin (C peptide). Results indicated that higher levels
      of family stress and lower levels of family resources as reported by fathers were
      significantly associated with poor metabolic control. Multiple regression
      analyses revealed that levels of family stress and resources were more strongly
      related to metabolic control than were disease variables such as C peptide
      levels. Moreover, family stress was directly associated with metabolic control,
      and family resources showed indirect linkages. Findings suggest that family
      stress and resources are potential areas for social work intervention in children
      recently diagnosed with diabetes.

PMID- 8288139
TI  - Stressors experienced by relatives of patients in an innovative rehabilitation
      program.
AB  - The social work component of this study was conducted for ethical reasons to
      monitor the impact on relatives of providing therapy to severely brain-injured
      patients on an innovative rehabilitation treatment program in an acute care
      hospital. The authors identify stressors experienced by the family caregivers.
      Findings are based on 450 interviews conducted by three research social workers
      during the 18-month study period with 78 family caregivers of the 37 patients.
      The results indicate that involvement in providing treatment was stressful,
      because of both the demands on the family and the unproven efficacy of the
      treatment. The authors recommend that a family's ability to provide treatment be
      clearly assessed before recruitment and that relatives' stress be monitored
      during their involvement. The findings emphasize the important role social
      workers can perform in identifying and monitoring such stress.

PMID- 8288140
TI  - Assessment of dementia patients and their families: an ecological-family-centered
      approach.
AB  - Demand for assessment and treatment of dementia patients and their families is
      expected to increase substantially by the end of this decade, considering current
      estimates of about 4 million dementia patients. This article guides social work
      practice in the assessment of dementia patients and their families using an
      ecological-family-centered (EFC) model of practice. A case presentation
      illustrates how to apply the ECF model while incorporating ethnically sensitive
      practice principles. The model organizes complex assessment issues that often
      arise when working with families of dementia patients and illustrates the
      significance of cultural diversity in case practice. Literature on families of
      dementia patients is reviewed, an intervention plan for the family system is
      outlined, and implications for practice are noted.

PMID- 8288141
TI  - In-hospital respite as a moderator of caregiver stress.
AB  - Data on family caregiver stress obtained before, during, and following respite
      suggest that stress was moderated by an in-hospital respite program for patients
      with Alzheimer's disease. Although short-term benefits may be realized for
      caregivers, in-hospital Alzheimer's respite care may present a particular risk
      for patient decline, adverse events, and institutionalization.

PMID- 8288142
TI  - Postpolio survivors: needs for and access to social and health care services.
AB  - A needs assessment survey of 268 polio survivors residing in Maine explored the
      incidence of postpolio syndrome as well as perceived need for and access to
      social and health care services. A large proportion reported experiencing
      postpolio syndrome. Although knowledgeable of their condition, a majority
      perceived that they had no access to knowledgeable physicians or social and
      health care services and most were having difficulty coping. Findings indicate
      that polio survivors' self-appraisal of their illness status is related to their
      perceived need for and access to social and health care services. The need for
      community-based services, including medical, rehabilitative, educational, and
      social work services, is indicated.

PMID- 8288143
TI  - A critical-incident stress debriefing program for hospital-based health care
      personnel.

PMID- 8288144
TI  - Building the social work literature in health.

PMID- 8288145
TI  - Managed care and managed competition: a primer for social work.

PMID- 8288146
TI  - Hispanic culture and family care of Alzheimer's patients.
AB  - Caring for Alzheimer's patients places tremendous burdens and strain on families.
      This study examined the ways cultural values and norms influence the experiences
      of Hispanic caregivers. The results revealed relationships between attitudes
      toward caregiving and a sense of burden and depression among the caregivers, with
      depression being related to stronger adherence to norms of filial support.
      Factors associated with increased burden include lack of time for oneself,
      dependency needs of the patient, and belief that one could be doing a better job
      as caregiver. Problems common to other groups of caregivers--feelings of anger,
      relationship and financial strain, and isolation--were not apparent. Although
      relatives provide affective support, the burden of instrumental assistance rests
      on the primary caregiver. These findings, as well as a reluctance to discuss
      problems outside of the family, call for active social work interventions.

PMID- 8288147
TI  - Redefining hospital social work: an embattled professional domain.

PMID- 8288148
TI  - Factors associated with participation in HIV antibody screening and results
      disclosure.
AB  - The Centers for Disease Control reported in October 1991 that many people at risk
      for human immunodeficiency virus (HIV) infection had not been tested for
      antibodies to HIV. This study identifies differences among 110 gay and bisexual
      men in three small cities in Pennsylvania who decided whether to be tested for
      antibodies to HIV and, if so, whether to return for results. These men were given
      self-administered questionnaires and were offered free and confidential HIV
      antibody tests. Fifty percent of the men refused testing. Of those tested, only
      35 percent returned to obtain test results. Contrary to other health prevention
      data, education was significantly and inversely related to being tested and to
      returning for results. Men who most often participated in the institutionalized
      gay community were least likely to be tested. The findings suggest that gay men
      who are most aware of the potential psychosocial problems associated with HIV
      antibody testing are more likely to avoid testing.

PMID- 8288149
TI  - Physicians mutual aid group: a response to AIDS-related burnout.
AB  - Physicians providing primary health care to people with AIDS are exposed to the
      same stressful experiences as other AIDS caregivers. Although mutual aid groups
      have proved useful in relieving stress for AIDS caregivers in general, physicians
      as a professional group present particular problems that impede their access to
      mutual aid. This article describes the origins and functioning of a physician's
      mutual aid group facilitated by the author. It offers suggestions related to
      overcoming resistance physicians might have to participating in such a group and
      reviews modalities that were found helpful in facilitating participants' ability
      to share emotional stresses within the group. The commitment of the physicians to
      the group over a prolonged period and their own testimony indicate that with
      appropriate facilitation, physicians under stress from providing care to people
      with AIDS can benefit from the experience of mutual aid that has been so
      beneficial to other caregivers.

PMID- 8288150
TI  - AIDS-related knowledge and attitudes of social workers in South Carolina.
AB  - This study examines the association between knowledge of acquired immune
      deficiency syndrome (AIDS) and skill among social workers in South Carolina and
      attitudes toward people with human immunodeficiency virus (HIV) and AIDS. A
      stratified random sampling method was used to obtain a representative sample of
      social workers in South Carolina. Findings show that AIDS-related knowledge and
      skill were significantly associated with improving the general attitudes of
      social workers toward HIV/AIDS clients. In addition to knowledge and skill
      related measures, other significant covariates of attitudes include levels of
      contact with HIV/AIDS clients and sensitivity to minorities. As with previous
      studies, demographic variables such as age and gender were not found to be
      significantly related to variations in attitudes toward HIV/AIDS clients.
      Furthermore, locality of practice and supervisory position did not significantly
      correlate with attitudes. The implications of these findings for social services
      agencies are discussed.

PMID- 8288151
TI  - Social work outreach to homeless people and the need to address issues of self
      esteem.
AB  - This article assesses self-esteem in a sample of homeless people from a major
      urban area. The findings indicate bivariate associations between low self-esteem
      and depression, family relationships, goal attainment, disability, health, and
      food deprivation. Multivariate analysis suggests that depression and poor health
      are the two most significant variables that contribute to low self-esteem. Social
      work outreach can provide services to positively influence homeless peoples'
      lives. First, however, it is important to facilitate proper psychosocial and
      psychiatric assessment, to make a diagnosis, and to provide on-site treatment.

PMID- 8288152
TI  - Effective services for bereaved spouses: a content analysis of the empirical
      literature.
AB  - To investigate the elements needed to serve bereaved spouses effectively, a
      content analysis of nine experimental studies on bereavement programs was
      conducted. A coding system was used to analyze the studies on five practice
      related variables: characteristics of the client, the practitioner, the
      intervention, the research methodology, and the outcome. Comparisons between
      effective and ineffective programs indicated that planned brief intervention is
      effective in preventing or reducing symptoms of morbid grief among spouses who
      are at high risk or in high distress. Findings also revealed the need for
      practice and research on bereavement to use an ecological framework and to
      address issues of human diversity.

PMID- 8288153
TI  - Of dirty sheets and worse: administration costs and staffing matters.

PMID- 8288154
TI  - Working with potentially assaultive clients.

PMID- 8288155
TI  - Metabolic control in streptozotocin diabetic rats following transplantation of
      microencapsulated pancreatic islets.
AB  - Microencapsulated islet grafts implanted into the peritoneal cavity of a variety
      of animal models of diabetes have been shown to reverse hyperglycaemia over
      prolonged periods without immunosuppression. Here, effects of these grafts on
      intermediary metabolites, diurnal blood glucose and glycated haemoglobin were
      studied in streptozotocin-diabetic Wistar rats. Following transplantation
      (approximately 3000 islets) glucose and the ketone 3-hydroxybutyrate fell
      significantly (glucose: 19.1 +/- 0.6 (SD) to 9.2 +/- 4.3 mmol/l, p < 0.01; 3
      hydroxybutyrate: 1.51 +/- 0.48 to 0.55 +/- 0.38 mmol/l, p < 0.02) and remained
      within/close to the normal range for at least four weeks. In control diabetic
      animals, values remained abnormally elevated. There was no difference in lactate,
      alanine or glycerol between the two groups. In transplanted animals there was a
      marked variation in blood glucose over a 24h period, values being low during
      daylight hours but with nocturnal peaks (up to 25 mmol/l) during the animals'
      normal feeding time. Glycated haemoglobin was also lower in transplanted animals
      but did not return to normal and the difference was not significant. In
      conclusion, microencapsulated islet grafts ameliorated the diabetic state.
      However, normal metabolic homeostasis was not achieved. The intraperitoneal site
      precludes direct graft vascular access and this may be a contributory factor.
      Additionally, daytime blood sugar values in murine models of diabetes may be a
      poor guide to graft function and glucose tolerance.

PMID- 8288156
TI  - Furosemide-induced hyperglycaemia: the implication of glycolytic kinases.
AB  - Hyperglycaemia is a well known adverse effect of therapy with diuretics. In
      adipose tissue, hydrochlorothiazide and furosemide inhibit the rate of glucose
      transport. In skeletal muscle, furosemide decreases the rate of glucose
      phosphorylation and glycolysis. However, whether furosemide has any direct effect
      on the activities of any of the glycolytic enzymes is not known. In the present
      study, the effects of furosemide on the activities of the hexokinase,
      phosphofructokinase and pyruvate kinase were examined. Pieces of skeletal muscle
      (quadriceps) and liver were obtained from 10 non-diabetic subjects during
      surgery. Tissues were homogenized and the activities of the enzymes were measured
      in the presence or absence of furosemide (0-1.5 mM). Furosemide inhibited the
      activity of all three key glycolytic enzymes. The concentration of furosemide
      required to inhibit phosphofructokinase in muscle was lower than that required to
      inhibit the activity of this enzyme in the liver or to inhibit the activities of
      hexokinase and pyruvate kinase in both muscle and liver. These direct effects of
      furosemide may contribute to the decrease in glucose utilisation following
      therapy with this and similar agents in man.

PMID- 8288157
TI  - Effects of glucose load on brain extracellular lactate concentration in conscious
      rats using a microdialysis technique.
AB  - Changes in the brain lactate concentration in cerebral extracellular fluid (ECF)
      during intravenous infusion of glucose and local administration of glucose were
      investigated in adult, conscious, unrestrained rats, with a microdialysis probe
      in the posterior hippocampus. The rats were infused intravenously with either 25%
      sucrose solution or 25% glucose solution at a rate of 16.6 microliters.min-1.100
      g-1 for three hours. The blood glucose concentration reached 17.0 +/- 2.6 mM at
      the end of the glucose infusion, and brain ECF glucose showed a parallel change
      with the blood glucose concentration and increased to 2.37 +/- 0.30 mM. However,
      blood and brain ECF glucose concentrations did not change in animals infused with
      the sucrose solution. On the other hand, the blood lactate concentration in the
      glucose-infused group also increased from 0.93 +/- 0.18 mM to 2.85 +/- 0.39 mM at
      the end of the glucose infusion, which was significantly higher than that
      measured in the sucrose-infused group. The blood lactate level in the glucose
      infused group returned to the basal level by the end of the experiment. Brain ECF
      lactate concentrations increased from 1.21 +/- 0.06 mM to 1.69 +/- 0.11 mM in
      glucose-infused animals, but did not change in the sucrose-infused animals. The
      brain ECF lactate concentration showed a positive correlation with the brain ECF
      glucose concentration in glucose-infused animals. Another group of rats was
      administered glucose locally for 90 min after substitution of artificial
      cerebrospinal fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288158
TI  - Prolactin stimulation of protein kinase C in isolated mouse mammary gland nuclei.
AB  - Prolactin (PRL) was found to stimulate protein kinase C (PKC) activity in a
      transient fashion in isolated nuclei derived from the mammary glands of 12-14 day
      pregnant mice. PKC activation was time and dose dependent and was blocked by
      staurosporine. With 10 ng/ml PRL a maximum stimulation of PKC occurred at 3 min,
      whereas with 50 ng/ml the effect was maximal at 2 min. After 5 min, the effect of
      PRL on PKC activity was no longer detected. Specificity of the PRL effect on PKC
      was established by showing that bovine growth hormone and insulin at 10 ng/ml had
      no effect on PKC activity. Multiple proteins in the nuclear preparations were
      shown to be phosphorylated by the addition of PKC derived from rat brain tissue.
      These studies have important implications regarding the possible direct effects
      of prolactin in the nucleus of mammary cells.

PMID- 8288159
TI  - Thyroxine-supported oxidation in the myeloperoxidase system.
AB  - Thyroxine and other iodothyronines (concentrations in the nanomolar range)
      stimulated the oxidation of NADH in the myeloperoxidase-H2O2-Cl- system. In the
      absence of chloride, thyroxine had only a marginal effect. This suggests that
      thyroxine increased the generation of chlorinating oxidants. A peroxidase
      catalysed oxidation product of thyroxine, 3,5-diiodotyrosine, was inactive. Pre
      incubation of thyroxine in the myeloperoxidase system showed that thyroxine was
      oxidized to a product capable of stimulating NADH oxidation. Reduction and
      alkylation of myeloperoxidase under nondenaturing conditions also increased the
      oxidative activity of the enzyme. It is postulated that both iodoacetamide and a
      thyroxine-derived oxidation product (presumably a quinone) alkylate sulphydryl
      groups near the active centre of myeloperoxidase making it more accessible for
      its substrate.

PMID- 8288160
TI  - Endocrine and metabolic effects of dexfenfluramine in patients with android
      obesity.
AB  - The effects of dexfenfluramine on 24-hour profiles of ACTH, GH, norepinephrine,
      insulin and FFA were studied in a group of obese male patients. A controlled
      comparison trial under metabolic ward conditions was conducted. Dexfenfluramine
      (15 mg twice daily) was given for 8 days, while patients adhered to a weight
      maintaining diet. 9 obese patients were treated with dexfenfluramine. 9 obese
      patients who were randomized on the basis one after another served as a control
      group. After a 3 day run-in period at 8 am, 10 am, and 4 pm, 8 pm and 12 pm, and
      8 am of the following day ACTH, GH, norepinephrine, insulin and FFA were measured
      before and during the 8th day of dexfenfluramine treatment. During the study body
      weight slightly decreased in both groups. In the DF group systolic and diastolic
      blood pressure declined during treatment. The norepinephrine levels were
      depressed during DF treatment over the entire day. The 24-hour profile of ACTH
      levels changed in the treatment group to a more distinct circadian rhythm with
      slightly higher levels in the morning and lower levels at night. The 24-hour
      profile of GH changed in the drug treated group with a diminished peak of GH
      secretion at night. Serum concentrations of insulin and FFA were decreased during
      DF treatment. The hormonal changes during dexfenfluramine treatment suggest that
      the drug affects endocrine mechanisms that may be involved in regulation of
      energy balance. Treatment with dexfenfluramine results in decrease of FFA. The
      mechanisms by which dexfenfluramine operates and displays its various effects on
      hormones and lipolysis have not been studied.

PMID- 8288161
TI  - Effects of an acute bolus growth hormone infusion on the human immune system.
AB  - This study was performed to examine the in vivo effects of a bolus of recombinant
      human growth hormone (r-hGH) on the human immune system. In a double blind
      placebo controlled cross over study, healthy volunteers were given 2 IU r-hGH as
      an intravenous infusion. r-hGH did not influence the subpopulations of blood
      mononuclear cells (BMNC), natural killer cell activity, in vitro proliferative
      responses or production of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL
      6, IL-8, tumor necrosis factor alpha (TNF alpha), TNF beta or interferon gamma in
      supernatants from BMNC stimulated with either lipopolysaccharide or
      phytohemagglutinin. However, two h after infusion a significant neutrocytosis
      occurred. It is concluded that a bolus infusion of r-hGH to healthy volunteers
      exerts only minor effects on the human immune system.

PMID- 8288162
TI  - Lipoprotein (a) in thyroid dysfunction before and after treatment.
AB  - Alterations of the lipid profile are a well known phenomenon in thyroid
      dysfunction. Thyroid hormones regulate lipid metabolism through various
      mechanisms, but a key role is played by the LDL receptor pathway. Thyroid hormone
      influence on Lipoprotein (a) (Lp[a]) metabolism is unknown; therefore we studied
      Lp(a) concentrations in a group of 29 hypothyroid patients with post-surgical
      hypothyroidism and in a group of 14 hyperthyroid subjects with Graves' disease
      before and after the thyroid function was normalized by treatment. In hypothyroid
      patients total and LDL-cholesterol markedly decreased after T4 treatment (342 +/-
      78 mg/dl before and 193 +/- 46 mg/dl after; 225 +/- 72 mg/dl before, 111 +/- 43
      mg/dl after respectively, p < 0.001). Also HDL-cholesterol and triglycerides
      decreased (from 75 +/- 22 mg/dl to 56 +/- 18 mg/dl and from 182 +/- 87 mg/dl to
      112 +/- 42 mg/dl respectively, p < 0.001). Lp(a) showed minor but not significant
      variations (median values 80 mg/l before 55 mg/l after treatment, p: N.S.). In
      hyperthyroid patients total and LDL-cholesterol increased after methimazole
      treatment (from 148 +/- 49 mg/dl before to 254 +/- 67 mg/dl after and from 87 +/-
      38 mg/dl before to 178 +/- 51 mg/dl after, p < 0.001). HDL-cholesterol increased
      (from 39 +/- 9 to 50 +/- 15, p < 0.01) while triglycerides were unchanged. Lp(a)
      levels slightly rose (median values 57 mg/l before 84 mg/l after treatment, p <
      0.05). These data suggest that the influence of thyroid hormones on Lp(a)
      metabolism is of minor entity and probably does not operate through the LDL
      receptor pathway.

PMID- 8288163
TI  - Cross-sectional study of percentual changes in total plasmatic fatty acids during
      pregnancy.
AB  - Total plasma fatty acids were analysed in 75 first trimester pregnant women, 32
      second trimester pregnant women, 27 women at delivery and 38 non-pregnant women.
      Eleven fatty acids were studied by capillar gas chromatography SP-column.
      Compared with non-pregnant women, in the first trimester there was a significant
      percentual increase in palmitic, palmitoleic, stearic and docosahexaenoic acids,
      whereas linoleic and eicosapentaenoic percentually decreased. Between the first
      and second trimester a significant increase in the proportion of palmitic acid
      and a significant percentual decrease in arachidonic acid was detected. Between
      the second trimester and delivery the aforementioned changes were more marked.
      Between the second trimester and delivery there was also a significant percentual
      increase in oleic and linolenic acids, whereas the proportions of stearic,
      linoleic, dihomogammalinolenic and docosahexaenoic acids significantly decreased.
      It is suggested that the intake in polyunsaturated fatty acids should be
      increased during pregnancy, specially in the third trimester.

PMID- 8288164
TI  - Comparison of plasma pancreastatin and GAWK concentrations, presumed processing
      products of chromogranin A and B, in plasma of patients with pancreatic islet
      cell tumors.
AB  - Plasma pancreastatin (PST) and GAWK, peptides processed from chromogranin A and
      B, were elevated in patients with various neuroendocrine tumors. In the present
      study, we measured plasma PST- and GAWK-like immunoreactivity (LI) concentrations
      in 12 patients with pancreatic islet cell tumors and evaluated them as a marker
      for these tumors. We also performed the gel filtration of the plasma from a
      gastrinoma patient and investigated the processing of PST and GAWK in plasma.
      Elevation of plasma PST-LI was found in 4 of 12 patients (33%) and elevation of
      plasma GAWK-LI was found in 6 of 12 patients (50%). A significant correlation was
      not found between plasma PST- and GAWK-LI concentrations of the patients. In the
      gel permeation chromatography of the plasma from a gastrinoma patient, PST-LI
      composed of a single peak but GAWK-LI composed of several components with wide
      range molecular weights.

PMID- 8288165
TI  - Effects of long chain free fatty acids on glucose-induced insulin secretion in
      the perfused rat pancreas.

PMID- 8288166
TI  - Stimulatory effect of thyrotropin (TSH) on interleukin-2 (IL-2) release from
      human peripheral blood lymphocytes. A dose-response study in vitro.

PMID- 8288167
TI  - Progestin effects on prolactin secretion and on immunoreactive prolactin cells in
      estradiol-treated ovariectomized rats.

PMID- 8288168
TI  - Changes in mood, anxiety, and personality disorders.

PMID- 8288169
TI  - Prize-winning videos on patients' well-being and on the experience of loss.

PMID- 8288170
TI  - Recognizing dissociative disorders in patients with chemical dependency.

PMID- 8288171
TI  - Mental health care reform: implications for social work.

PMID- 8288172
TI  - Lithium's role in hyperparathyroidism and hypercalcemia.

PMID- 8288173
TI  - A review of supportive psychotherapy, 1986-1992.
AB  - OBJECTIVE: In 1986 a review of literature on individual supportive therapy
      concluded that although many clinicians had a low regard for this treatment
      approach, it should be taken more seriously. In this paper the author reviews the
      literature on supportive therapy from 1986 to 1992 to determine whether it has
      received increased attention. METHODS: MEDLINE and PsycINFO data bases were used.
      Studies were chosen based on their relevance to supportive psychotherapy and
      quality of scholarship. RESULTS AND CONCLUSIONS: The quantity and quality of
      writing reflect heightened interest in supportive psychotherapy during the past
      six years. It is now securely ensconced in psychodynamic theory, and many
      clinicians have agreed on strategies and techniques. They include strengthening
      the therapeutic alliance, environmental interventions, education, advice and
      suggestion, encouragement and praise, limit setting and prohibitions, undermining
      maladaptive defenses while strengthening adaptive defenses, and emphasis on
      strengths and talents. Training programs have not kept pace with advances in
      knowledge and techniques. Further study of the use of supportive therapy with
      patients in specific diagnostic groups is recommended, as is more attention to
      this approach in clinical training and supervision.

PMID- 8288174
TI  - Reducing obstacles to affiliation with alcoholics anonymous among veterans with
      PTSD and alcoholism.
AB  - Alcohol use is prevalent among Vietnam veterans who suffer from chronic combat
      related posttraumatic stress disorder (PTSD). Although Alcoholics Anonymous (AA)
      is the mainstay of ambulatory alcoholism treatment, adherence to particular
      components of the AA philosophy may prove especially challenging for alcoholic
      Vietnam veterans with PTSD. The authors describe elements of AA's philosophy,
      such as "surrendering" to a "higher power," making amends to persons one has
      harmed, and sharing one's story publicly, that may be difficult for the Vietnam
      veteran with PTSD. The authors suggest that an important factor in the successful
      affiliation of these patients with AA is their capacity to separate their alcohol
      related problems and treatment from their PTSD symptoms and treatment and to
      accommodate dual identities as both an alcoholic and a traumatized soldier.
      Preparing such patients for AA by reframing some of the 12 steps is recommended.

PMID- 8288175
TI  - Participation in an outreach-based coupon distribution program for free methadone
      detoxification.
AB  - OBJECTIVE: The purpose of the study was to identify characteristics of injection
      drug users that predicted whether subjects would redeem a coupon for free
      methadone detoxification and to determine whether they were more likely to
      participate in a 90-day detoxification program than in a 21-day program. METHODS:
      A total of 4,390 current heroin users recruited through street-based outreach
      programs in Newark and Jersey City, New Jersey, accepted coupons for either 21 or
      90 days (randomly determined) of methadone detoxification after they were
      interviewed about drug use and sexual behavior. Subjects also gave blood samples
      for HIV testing. Multiple regression analysis was used to determine variables
      associated with coupon redemption. RESULTS: Of 4,390 coupons distributed, 58.5
      percent were redeemed; the 90-day coupons were redeemed at a significantly higher
      rate (59.9 percent) than the 21-day coupons (56.9 percent). Among coupon
      redeemers, 43.6 percent had never received formal drug treatment, and 44.9
      percent were HIV seropositive. Frequent heroin use, previous drug detoxification,
      frequent drug injection, cleaning needles with bleach, nonblack race, Hispanic
      ethnicity, and Newark residence each significantly predicted coupon redemption.
      CONCLUSIONS: Outreach-based coupon distribution may be used to recruit large
      numbers of never-treated and HIV-infected drug users into treatment. The 90-day
      coupon was more effective in facilitating treatment entry.

PMID- 8288176
TI  - Comorbid substance abuse and recovery from acute psychiatric relapse.
AB  - OBJECTIVE: The study investigated whether chronic mentally ill patients whose
      psychiatric relapse was complicated by active substance abuse recovered from
      relapse at a different rate than similar patients with no comorbid substance
      abuse. METHODS: A total of 401 patients involuntarily hospitalized on a short
      term psychiatric treatment unit received a urine toxicology screen on admission;
      the severity of their psychiatric symptoms was rated on the fifth day of
      hospitalization using the Brief Psychiatric Rating Scale (BPRS). Differences in
      scores between patients who had positive screens and those who had negative
      screens were evaluated for various diagnostic groups. RESULTS: Patients who had a
      positive screen and a primary discharge diagnosis of psychoactive substance abuse
      had a BPRS total score indicating less psychopathology than similarly diagnosed
      patients with negative screens. Patients who had positive screens and a diagnosis
      of personality disorder had some BPRS subscale scores indicating greater
      psychopathology than their counterparts with negative screens. No other
      significant differences in recovery rates between the two groups were found,
      although comparisons indicated trends toward faster recovery in some areas of
      functioning by schizophrenic patients with positive screens and affective
      disorder patients with negative screens. CONCLUSIONS: Results suggest that use of
      a urine toxicology screen and the BPRS early in treatment may aid in assessing
      the acute course of several psychiatric disorders and the effect of comorbidity.

PMID- 8288177
TI  - Staffing patterns in rural community support programs.
AB  - OBJECTIVE AND METHODS: Rural mental health programs are thought to have
      difficulty recruiting and retaining qualified staff and to have excessively large
      caseloads per staff member. The authors surveyed 12 community support programs in
      small cities and rural areas of Wisconsin to determine staff size and
      characteristics, staff-to-client ratios, and the relative use of paraprofessional
      staff and professional staff, excluding psychiatrists. RESULTS: The programs
      surveyed had an average of 5.6 full-time-equivalent caregiving staff and an
      average caregiver-to-client ratio of 1 to 13. Caregiving staff were predominantly
      female, had been in the mental health field a mean of 8.8 years, and received an
      average salary of $20,732. Although program directors indicated that about one
      fifth of staff left in the previous year, they reported little difficulty
      recruiting staff. Thirty-eight percent of all caregivers were paraprofessionals;
      in several programs, more than half the caregivers were paraprofessionals. Use of
      paraprofessionals is more common in rural programs; thus caregivers in those
      programs are likely to have lower levels of salary and experience. CONCLUSIONS:
      The community support programs in the sample employed experienced caregivers and
      had staff-to-client ratios that were close to the ratio recommended for such
      programs by Wisconsin legislation. The survey findings suggest that claims of
      acute staffing problems in rural community support programs need to be examined
      more closely, with attention to the relationship between staff characteristics
      and client outcomes.

PMID- 8288178
TI  - Types of weapons and patterns of use in a forensic hospital.
AB  - OBJECTIVE: The purpose of this study was to describe types of weapons and weapon
      use patterns among inpatients at a state forensic hospital to assist staff in
      evaluating the weapon-screening program. METHODS: Data for a five-year period
      were drawn from special incident reports, hospital police crime reports, and
      supervisory logs to document weapon use in a 973-bed, all-male maximum security
      forensic hospital. Weapons were categorized as weapons of opportunity (objects
      available at the site of the attack) and manufactured or contraband weapons.
      Repeat use of weapons by a patient was documented. RESULTS: Weapon use was
      relatively rare. During the five-year period less than 3 percent of inpatients
      used weapons, and less than 3 percent of violent incidents involved weapon use.
      Available objects were used in most attacks. Only 17 patients were responsible
      for a fourth of all weapons assaults, and these patients repeatedly used the same
      types of available objects, particularly furniture. Staff and patients were
      targeted equally in the weapon assaults. CONCLUSIONS: Weapon-screening programs
      may prevent weapon carrying but not weapon use. Detailed histories of weapon use
      should be part of each patient's assessment and should be made known to staff.

PMID- 8288179
TI  - Police referral to psychiatric emergency services and its effect on disposition
      decisions.
AB  - OBJECTIVE: Some clinicians and researchers have questioned the appropriateness of
      police referrals to psychiatric emergency services and have suggested that police
      exercise undue influence on hospital admission decisions. The purpose of this
      study was to test these assertions. METHODS: Research clinicians in nine
      emergency services in California observed staff evaluations of 772 cases and
      rated patients' symptom severity, danger to self or others, and grave disability.
      They also reviewed the criminal justice records of these patients both before and
      for 18 months after the index evaluation. A total of 186 patients referred by
      police were compared with 577 patients not referred by police. RESULTS: Patients
      brought by police were more likely to be subsequently hospitalized, but they were
      also more psychiatrically disturbed. They were more dangerous to others and more
      gravely disabled. They were no more likely to have a criminal record than
      patients not referred by police. CONCLUSIONS: Police did not exercise undue
      influence on dispositions nor were the patients they brought in more "criminal"
      than others.

PMID- 8288180
TI  - Why and how to establish a computerized system for psychiatric case records.
AB  - Based on experience with successful implementation of an on-line computerized
      psychiatric case record system in a psychiatric hospital in Israel, the authors
      discuss the advantages of such systems and outline the process of converting
      paper records to computerized records. Computerized records can save time by
      automatically issuing routine reports, improve clinical practice, simplify
      quality assurance, and ease collection and analysis of data for research. The
      process of converting paper records to computerized records can begin with
      analysis of the hospital's reporting requirements and creation and pilot testing
      of structured paper forms with a multiple-choice format that is eventually
      incorporated into the computer program. The authors recommend an on-line
      computerized record system with direct input of data because such a system can be
      used for case audits and can generate reports, treatment plans, and medication
      orders without removing records from circulation. Other advantages include the
      system's usefulness in electronic communication within and outside the hospital.

PMID- 8288181
TI  - Benefits of a structured format for paper and computerized psychiatric case
      records.

PMID- 8288182
TI  - A computer-assisted inpatient psychiatric assessment and treatment planning
      system.

PMID- 8288183
TI  - Coping-skills training versus a problem-solving approach with schizophrenic
      patients.

PMID- 8288184
TI  - HIV risk activity among persons with severe mental illness: preliminary findings.

PMID- 8288185
TI  - Helping mentally ill mothers.

PMID- 8288186
TI  - [A study on P21(ras) in human lung cancer and body fluid of cancer patients].
AB  - The McAb of anti-P21(ras) has been used to screen 9 cases of human lung cancer
      tissues, 18 cases of samples and 2 cases of hydrothorax samples of lung cancer
      patients by means of PAGE-immunoblots. The expression of ras gene was found in 8
      cases of human lung cancer among which the expression of 4 cases was higher than
      that of normal control. P21(ras) has not been detected in serum and hydrothorax
      samples of cancer patients. The present study indicated that there was P21(ras)
      in human lung cancer and normal control and the expression level of ras gene in
      lung cancer was related to the differentiation of cancer.

PMID- 8288187
TI  - [Application of in situ hybridization using digoxigenin--labeled HBV DNA probe
      and comparison with biotinylated probe].
AB  - A method of in situ hybridization for HBV DNA on liver tissue with digoxigenin
      labeled probe is described. We have detected the HBV DNA of sixteen liver
      biopsies. The results showed that the sensitivity and specificity of digoxigenin
      labeled probe for in situ hybridization were hig er and stronger then those of
      biotinylated probe. The practicality of digoxigenin-labeled probe is better. It
      is an excellent non-radioactive probe for in situ hybridization, which may
      eventually replace the biotinylated probe. The localization of HBV DNA in
      hepatocytes could be classified into 4 types, namely, the whole cytoplasmic,
      focal cytoplasmic, whole nucleic and nuclear membranous-nucleolus. The results of
      in situ hybridization using digoxigenin-labeled probe could reflect the free or
      integrated status of HBV genome and the levels of its genomic replication in
      hepatocytes. The procedure of in situ hybridization using digoxigeninlabeled
      probe was also discussed.

PMID- 8288188
TI  - [Pathogenic factors of postischemic ventricular dysfunction and effects of
      magnesium].
AB  - To investigate the mechanism of myocardial; tunning, a Langendorff model of rat
      hearts (n = 18) underwent 15 min ischemia with coronary flow at 0.2 ml/min and 10
      min reperfusion with Ringer's solution of 1.06 mmol/L Mg2+. Histological exam
      revealed no myocardial necrosis. However, the recovery of pressure product (RPP)
      was only 77% compared with control period. The myocardial Ca2+ content and water
      content were significantly increased (P < 0.01, vs control hearts). Pretreatment
      with high concentration of Mg2+ (2.4 mmol/L) improved the recovery of
      postischemic ventricular function, attenuated the Ca2+ overload and myocardial
      edema. The results indicated that a brief period of low-flow ischemia could
      produce a postischemic ventricular dysfunction-the myocardial stunning. Calcium
      overload and myocardial edema might be two pathogenic factors. An increased Mg2+
      had a protective effects on postischemic ventricular dysfunction, which may
      involve the following mechanisms: reduced Ca2+ overload and attenuated myocardial
      edema.

PMID- 8288189
TI  - [Study on the induction of active immunity in human by injecting human anti-HBs
      antibodies].
AB  - One hundred and three health volunteers were injected with various doses of human
      anti-HBs (Ab1). The anti-idotypic antibodies (Ab2) and anti-antiidiotypic
      antibodies (Ab)3 in sera were tested at intervals of 30 days with ELISA. We found
      that the dynamic changes between Ab2 and Ab3 of immune sera were cyclical by way
      of their interaction and the Ag-specific Ab3 were the same as Ab1 in specificity.
      The results reconfirmed that exogenous human anti-HBs could induce active
      immunity by activation of idiotypic network and regulation in human body
      suggesting that injection of Ig into body could bring about not only passive
      immunity but also active immunity.

PMID- 8288190
TI  - [Development of hybridomas secreting monoclonal anti-idiotypic antibodies that
      bear the internal image of the terminal trisaccharide of PGL-I].
AB  - Two hybridomas designated as F7B7 and F7B9 secreting monoclonal anti-idiotypic
      antibodies against terminal trisaccharide of PGL-I were developed by fusion of
      SP2/0 cells and spleen cells of BALB/c mouse immunized with mouse monoclonal anti
      trisaccharide of PGL-I (MAb1-E10F1). To characterize the F7B7, the following
      results were obtained. First, F7B7 reacted with MAb1-E10F1 specifically.
      Secondly, the cross ELISA neutralizing tests gave positive results. The binding
      of anti-trisaccharide positive serum with trisaccharide (contained in semi
      synthetic antigen, NT-O-BSA) was inhibited F7B7 and the degree of inhibition
      showed dose-dependent manner. The binding of anti-trisaccharide positive serum
      with F7B7 was inhibited by NT-O-BSA and the degree of inhibition also showed dose
      dependent manner. It was concluded that the hybridoma F7B7 is able to secrete
      monoclonal anti-idiotypic antibodies that bear the internal image of
      trisaccharide of PGL-I. The potentials and advantages of monoclonal anti
      idiotypic antibody F7B7 as surrogate antigen in the serodiagnosis of leprosy have
      been discussed.

PMID- 8288192
TI  - [Restriction endonuclease analysis of leptospiral DNA from different serogroup
      and serovar].
AB  - The DNAs of different serogroups and serovars of leptospires were analyzed with
      seven kinds of restriction endonuclease (Bam HI, Bgl II, Cfo I, Eco RI, Hind III,
      Kpn I and Pst I). The results showed that there are significant differences among
      the leptospiral DNAs of different serovars, especially in the high molecular
      weight region, but the patterns of different strains belonging to the same
      serovar are similar. In addition, Cfo I and Eco RI are more effective for
      differentiating leptospires.

PMID- 8288191
TI  - [Production and identification of monoclonal anti-idiotype antibodies against
      anti-phenolic glycolipid-I antibody of Mycobacterium leprae].
AB  - Hybridoma (4C4) secreting monoclone anti-idiotype antibody (McAb2) against anti
      phenolic glycolipid-I (PGL-I) antibody (Ab1) was produced by fusion of SP2/0
      myeloma cells and spleen cells of syngeneic mice which had been previously
      tolerant to human IgM 4C4 monoclone anti-idiotype antibody was identified with a
      series of experiments including competitive and neutralizing inhibition ELISA. It
      was found that the binding of McAb2 with rabbit anti-PGL-I antibody could be
      competitively inhibited by NT-O-BSA (synthetic analog of PGL-I) and neutralized
      by polyclonal anti-PGL-I antibody derived from various origins (human or rabbit);
      McAb2 could block the binding of purified human Ab1 with NT-O-BSA. The assay of
      McAb2 as mimic antigen demonstrated that McAb2 could substitute for NT-O-BSA in
      leprosy serodiagnosis. These results show that anti-idiotype antibody produced by
      4C4 is a monoclone anti-idiotype antibody bearing internal image of PGL-I and
      possibly can be used in leprosy serodiagnosis.

PMID- 8288193
TI  - [Amplified 23S rRNA gene of 52 strains of Leptospira and detection of leptospiral
      DNA in 55 patients by PCR].
AB  - Based upon the polymerase chain reaction (PCR), We have developed a sensitive
      assay for Leptospira interrogans, the agent of leptospirosis. DNA amplification
      was carried out using primer A: 5'GATCTAATTCGCTGTAGCAGG3' and primer B:
      5'ACTTTCACCCTCTATGGTCGG3'. After 30 cycles of amplification, the product could be
      detected by agarose gel electrophoresis. A segment (124 bp) was amplified in all
      strains of L. interrogans including 20 Serogroups, 49 Serovars tested, but it was
      not detected in Patoc I strain, Serovar patoc of Leptospira biflexa and 3055
      strain of Leptonema illini (both of which are nonpathogenic). All of the serum
      (first time) which proved either by blood culture or MAT showed that positive
      rates were 100%. Leptospiral infection in humans and some domestic animals leads
      to one or more of a variety of manifestation and persists through a considerable
      duration of time. However it is relatively difficult to demonstrate the presence
      of leptospires in serum. The serum (second time) obtained from 55 patients with
      leptospirosis (6-60 days after on set) showed that PCR positive rates were 74.55%
      (41/55). The PCR positive rates for healthy subjects were 15% (3/20), P < 0.001.
      The diagnosis of leptospirosis by using PCR may become a significant addition to
      the routine laboratory diagnosis and a valuable technique for the investigation
      of leptospirosis pathogenesis.

PMID- 8288194
TI  - [Pharmacokinetic studies on 99mTc-NGA in human].
AB  - Two normal subjects and three patients with hepatic disease were intravenously
      injected each with a single dose of 99mTc-NGA (galactosyl-neoglycoalbumin), a
      liver receptor imaging agent. The results showed that pharmacokinetics of 99mTc
      NGA accorded with the two compartment open model. In the normal subjects, T1/2
      alpha and T1/2 beta averaged 1.65 and 19.39 min respectively, indicating a rapid
      distribution process and a slow elimination process. There were significant
      differences in pharmacokinetics of 99mTc-NGA between the normal subjects and the
      patients with hepatic disease, and therefore the relevant parameters are of
      importance for the evaluation of hepatic function.

PMID- 8288195
TI  - [Viscoelastic property alterations in patients with rheumatic heart disease and
      congestive heart failure].
AB  - Few papers on alteration of whole blood viscoelastic properties in patients with
      congestive heart failure (CHF) have been reported. In this study viscoelastic
      property parameters were measured in 63 consecutive patients with rheumatic heart
      disease and CHF. All subjects were divided into four groups according to NYHA
      classification of heart function. There were 14 class I, 16 class II 20 class III
      and 13 class IV. Contraves low-shear-30 rheometer was used for measuring the
      viscoelastic parameters. The results demonstrated that there was no significant
      difference of these parameters between class I and class II, that the apparent
      viscosity, AI and eta' in class III were higher than those in class I, and that
      eta 0.512, eta 5.96 AI, eta', eta" and G' in class III were higher than those in
      class II. All viscoelastic parameters but eta p in class IV were markedly higher
      than those in other groups. However, there were no statistically significant
      difference of eta p among all subjects and nor significant difference of these
      parameters between male and female were noted. There was a negative correlation
      between viscoelastic parameters and heart function parameters by pulse Doppler
      echocardiography (peak flow velocity, stroke volume and cardiac output). The
      results also showed a significant direct correlation between eta 0.512 AI, and
      eta" and the heart function parameters mentioned above.

PMID- 8288196
TI  - [Fast identification of Salmonella by chemiluminescent photographic detection].
AB  - Salmonella anatis was identified by the chemiluminescent photographic detection
      technique established in this lab. The horseradish peroxidase labelled antibody
      was incubated with the bacteria immobilized on nitrocellulose film; after
      washing, the film was contacted with a filter paper with absorbed
      chemiluminescence substrate solution. Twenty minutes of exposure of the
      chemiluminescence produced to X-ray film gave the positive results. As few as one
      hundred bacteria could be detected in about 2h. The tests showed that the
      specificity of the method is good.

PMID- 8288197
TI  - [Pathology of muscle contracture caused by injection and activity of
      phosphochesterase and insulin receptor].
AB  - The animal model of muscle contracture caused by injection was set up in the
      experiment. We used the model for excessive healing studies and researched the
      changes in its pathology, and activity of phosphochesterase and insulin receptor
      in this model. The experimental results revealed that the pathologic changes
      belonged to excessive proliferation of connective tissue (excessive healing).
      When occurred muscle degeneration, infiltration of inflammatory cells,
      proliferation of fibroblasts and descending of collagen fibers, the activity
      level phosphochesterase and insulin receptor became higher. The excessive healing
      occurrence may have something to do with the changes of phosphochesterase and
      insulin receptor.

PMID- 8288198
TI  - [Subtyping of GC globulin in human semen stain].
AB  - The group-specific component (GC) is an alpha 2 globulin with high genetic
      polymorphism in serum. There is also a little amount of GC in human semen. Pflug
      and Potsch-Schneider independently carried out GC subtyping of human semen stain
      with immobilized pH gradient gel isoelectric focusing (IPGIF) followed by ELISA
      in 1988. We report a new method there to subtype GC in human semen stains. First,
      the GC globulin was separated by polyacrylamide gel isoelectric focusing with pH
      4.2-4.9 Pharmalyte. Then, it was immunoblotted to cellulose acetate membranes.
      Finally, the protein bands were shown by ELISA using horseradish peroxidase
      linked secondary antibody system. All the 17 semen stains of volunteers were
      subtyped successfully. This method is easy to learn and convenient for applying
      in case work.

PMID- 8288199
TI  - [Subtyping of PiM in human serum and semen by modified isoelectric focusing].
AB  - An isoelectric focusing of Pi pretreated with neuraminidase is reported.
      Subtyping of PiM in human semen was successfully carried out for the first time.
      This has provided a new approach for individual identification in sexual crime.

PMID- 8288200
TI  - [Isolation and purification of alpha -1 acid glycoprotein from human sera].
AB  - Alpha-1 acid glycoprotein, also named orosomucoid (ORM), is a serum protein with
      genetic polymorphism. This paper describes a two-step procedure for purifying ORM
      from human sera. The procedure consists of both anion exchange chromatography on
      a DEAE-Sephadex-A50 column and affinity chromatography on a Reactive Blue 2
      Sepharose CL-6B column. The purified ORM identified by polyacrylamide gel
      electrophoresis, SDS-polyacrylamide gradient gel electrophoresis,
      immunoelectrophoresis and immunodiffusion was homogeneous and reacted
      specifically with a commercial anti-ORM serum (Sigma). The molecular weight of
      the purified ORM was about 41 kd.

PMID- 8288201
TI  - [Study on estrogen and progesterone receptors in endometriosis and adenomyosis].
AB  - Estrogen and progesterone receptors (ER and PR) in 18 cases of ovarian
      endometriosis and 13 cases of adenomyosis were determined with dextran coated
      charcoal (DCC) method. The levels of ER and PR in those specimens were lower than
      those of normal endometrium. Among the 18 cases of ovarian endometriosis, 6
      (33.4%) were negative for PR, which accounted for the unsatisfactory results of
      progesterone treatment for some endometriosis. In the 13 cases of adenomyosis
      there were 10 (76.9%) showing positive PR. It is suggested that the hormone
      therapy may be useful to treat those young patients with adenomyosis instead of
      surgery. The correlation of the ER and PR levels, the treatment and prognosis in
      endometriosis and adenomyosis are worth further studying.

PMID- 8288202
TI  - [Study on 125I-labeled human chorinic gonadotropin after purification through gel
      electrophoresis].
AB  - Radioiodination of HCG with 125I Na using chloramine-T is widely employed.
      However, 125I-HCG damages in storage and thus results in decrease of
      immunological and biological activities. When 125I-HCG was in store as long as 30
      days, the immunological activity and biological activity decreased from 100% to
      33.1% and 44.0%, respectively. We used polyacrylamide gel electrophoresis to
      purify 125I-HCG which had been kept in store for 30 days since radiolabeling, and
      we found the binding capacities of purified 125I-HCG increased. The combination
      rates of purified 125I-HCG with antibody and receptors accounted for 90.5% and
      95.3% of those of 125I-HCG 1 day after radiolabeling. These results suggest that
      125I-HCG which has been stored for a period since radiolabeling should be
      purified before use.

PMID- 8288203
TI  - [Line width addition method and its application to biologic materials emission
      spectrum analysis].
AB  - Using alternating current are grating spectrograph, and self-made recording
      microphotometer for line contour and accurate measurement of line width, we
      measured the concentration of Cu and Ca in serum-like synthetic standard solution
      with line width addition method. The experimental results had better linearity,
      reproducibility and higher precision compared with those by density method,
      suggesting that line width method is better than density method in the analysis
      of biologic material concentration.

PMID- 8288204
TI  - [The distribution of normal oral flora in 49 healthy children and juvenile].
AB  - The frequencies and proportions of predominant cultiv ableoral bacteria
      associated with 49 healthy children and juvenile (6-25 yr old) were studied. A
      total of 72 bacterial species belonging to 28 genus were detected in 195 samples
      of saliva, fissure plaque, supragingival plaque, and subgingival plaque. The
      predominant bacteria were Oral streptococci, Neisseria, Actinomyces,
      Capnocytophaga, Bacteroides and Fusobacterium in the normal oral cavity of
      healthy children and juvenile. There were differences in the distribution of the
      predominant flora, e.g. Fusobacterium and Bacteroides had higher incidence and
      proportion in the subgingival plaque than in the fissure plaque.

PMID- 8288205
TI  - [A study on PEFV curves in adolescents].
AB  - We measured the PEFV curves in 557 adolescents aged from 6 to 19. Among them 200
      were measured for MEFV curves additionally. The multiple regression equations of
      FVC and VFRC were simultaneously set up. The result indicated that the indexes
      increased with the growth of age. At the beginning stage (6-14 years) there was
      no difference in the indexes between boys and girls. Later in the age range from
      14-16 years there were two cross points. Lastly (after 16 years) the indexes of
      the boys were much higher than those of the girls. The results suggest that the
      measurement of VFRC is a possible sensitive index to reflect the lung function
      variation, because it has not been influenced by the volume history.

PMID- 8288206
TI  - [Pharmacokinetics of ciprofloxacin in young healthy volunteers].
AB  - Pharmacokinetic studies on ciprofloxacin were carried out in 6 young healthy
      volunteers. Serum and urine levels of ciprofloxacin were measured by reversed
      phase high performance liquid chromatography. The drug obeyed one-compartment
      model kinetics in serum. The mean peak serum concentration, time to peak
      concentration and the area under the curve were 4.17 +/- 1.05mg/L, 1.75 +/- 0.40h
      and 18.09 +/- 2.69mg/L.h respectively after oral administration of 500mg of
      ciprofloxacin tablet. The elimination half life was 2.34 +/- 0.81h and the
      apparent volume of distribution was 3.71 +/- 0.75L. The urinary rate of
      ciprofloxacin over 24h after dosing was 34.22 +/- 6.57%. These data indicate that
      ciprofloxacin is easily absorbed and its concentration reaches the peak level
      rapidly. There are high levels of drug both in serum and urine.

PMID- 8288207
TI  - [Study on dissolution rate and bioavailability of norfloxacin capsule by UV
      spectrophotometry].
AB  - The dissolution rates and bioavailability of norfloxacin in seven batches of
      norfloxacin capsules produced by five pharmaceutical factories were studied with
      rotating basket and UV-spectrophotometry. The results showed that the T50, Td and
      m of the samples had obvious differences, and the correlation between the
      dissolution rate and bioavailability differed very obviously. The method used is
      simple and convenient. So UV-spectrophotometry is one of the methods for the
      assay of norfloxacin preparations in vitro and in vivo.

PMID- 8288208
TI  - [The pharmacodynamics of troxipide on experimental gastric ulcers in rats].
AB  - Effects of troxipide (Ku-54) on various experimental gastric ulcers in rats were
      studied. Ku-54 showed a dose-dependent antiulcerous action at 100, 200 and 300
      mg/kg (particularly 300 mg/kg) p.o. in water-immersion stress, pylorus ligated
      and acetic acid reduced rats. The effect of cimetidine (CIM) (600 mg/kg) on water
      immersion stress rats was significantly higher than that of Ku-54(300 mg/kg). On
      the other hand, the effect of Ku-54 (300 mg/kg) was higher than that of CIM (600
      mg/kg) on the pylorus ligated and acetic acid reduced groups. The antiulcerous
      action of Ku-54 (300 mg/kg) was not related with the content and the pH of
      gastric juice.

PMID- 8288209
TI  - [Prevention of reserpine induced experimental gastric ulcer in rat with
      amoxicillin a report of preliminary controlled study].
AB  - In recent years, amoxicillin (A) has been proved very effective in clearing
      helicobacter pylor (HP) and promoting ulcer healing. Is the cure due solely to
      the clearance of HP? Forty three Wistar rats were randomized into four groups to
      investigate the efficacy of A in preventing the experimental ulcer induced by
      reserpine and compare it with that of ranitidine (R) and antacid weishuping (W).
      A normal saline (NS) group was used as control. The total numbers of ulcer
      induced per rat for the NS, W, R and A groups were 7.8 +/- 5.1, 2.2 +/- 3.2, 1.0
      +/- 1.2 and 2.1 +/- 1.9, respectively. The ulcer indices were 20.8 +/- 13.2, 4.5
      +/- 7.7, 2.0 +/- 3.7 and 4.5 +/- 3.9, respectively. No HP was identified. The
      results indicated that A, R and W were all effective in preventing reserping
      induced ulcer with no significant difference (P > 0.05); they were significantly
      more effective than NS (P < 0.05). Since A is not an antacid and no HP existed in
      the experimental rats, there must be a mechanism of A involved in the prevention
      of experimental ulcer.

PMID- 8288210
TI  - [Analysis on postoperative prognosis in relation to blood ketone body ratios in
      surgical patients with liver disease].
AB  - Eighty-one patients with liver disease were studied for the postoperative changes
      in the arterial blood ketone body ratio (KBR) and routine liver function tests.
      The postoperative patients were classified into three groups-according to the
      postoperative changes in KBR. In the 54 patients of group A, KBR did not decrease
      to below 0.7, only 2 cases with complications (3.7%); in the 25 patients of group
      B, KBR decreased transiently to 0.4-0.7 and then increased to over 0.7, 9 cases
      with complications (36.0%), but they were ameliorated concomitantly with the
      restoration of KBR; in the 2 cases of group C, KBR decreased irreversibly to
      below 0.4, and a variety of complications occurred, so the patients finally died
      of multiple organ failure (MOF). It was found that routine liver function tests
      were less reliable direct indicators for the onset of postoperative hepatic
      insufficiency than KBR, which reflected the oxidoreduction state of liver
      mitochondria.

PMID- 8288211
TI  - [Evaluation of pulmonary arterial pressure by pulsed Doppler echocardiography
      compared with cardiac catheterization].
AB  - Twenty-six patients undergoing right cardiac catheterization were examined by
      pulsed doppler echocardiography (PDE), spectrum analysis of the shape of flow
      velocity curve of the pulmonary arteria during systole was made. Pulmonary
      arterial pressure (PAP) was qualitatively and qualitatively evaluated by right
      ventricular systolic time interval (RSTI) derived from pulmonary doppler blood
      flow velocity pattern. The correlation between PAP and the values of RSTI was
      evaluated, multiple stepwise regression analysis was performed. The pulmonary
      flow pattern and the values of RSTI measured from right ventricular outflow tract
      (RVOT) and main pulmonary artery (MPA) were compared. The results showed that: 1.
      Qualitative evaluation of PAP: (1) the triangular configuration of the pulmonary
      flow pattern was the feature of the pulmonary ejection flow in pulmonary
      hypertension (PH). (2) AT < 100ms AT/ET < 0.30 and PEP/AT > 1.1 indicated PH
      (PAMP > or = 2.7 kPa, AT < 100 ms, sensitivity 92.3%, specificity 100%). 2.
      Quantitative evaluation of PAP: (1) simple regression analysis: AT, AT/PEP
      especially AT showed a good inverse correlation with PAP, which was improved when
      a logarithmic function was applied, but not improved by the square root of heart
      rate. The liner regression equation and the correlation coefficient were: log
      PASP = -6.3617 AT +2.825 (r = -0.7925, P < 0.001); log PADP = -0.4569 AT +74.182
      (r = -0.8513, P < 0.001); log PAMP = -0.0073 AT +2.198 (r = -0.8635, P < 0.001).
      (2) multiple stepwise regression analysis: the stepwise analysis of six
      parameters (PEP, ET, AT, AT/ET, AT/PEP, square root of R-R) showed that AT, PEP
      were the best parameters correlated with PAP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288212
TI  - [The effects of phenytoin and carbamazepine on the cognitive function of
      epileptic patients].
AB  - We made a comparative study of the cognitive function of 60 epileptic patients
      before and after the use of phenytoin (DPH) and carbamazepine (CBZ). Five types
      of neuropsychological tests were adopted. Although both DPH and CBZ affected
      cognitive function, the degrees of their effects were not the same. DPH affected
      cognitive function in a broad field, including concentration, remembrance,
      psychological motor speed and mental processing, whereas CBZ had only slight
      effect on perception and motor speed. It is stressed that cognitive function
      disorder caused by antiepileptic drugs should be early detected by synchronous
      examinations of the level of antiepileptic drugs and the neuropsychological
      functions.

PMID- 8288213
TI  - [Vascular malformation of posterior cerebral artery in supertentorium].
AB  - Seventeen cases of vascular malformation of posterior cerebral artery in
      supertentorium from 1973 to 1991 are reported. These patients accounted for 8.8%
      of the total supertentorial vascular malformations during the same period. Their
      ages ranged from ten to forty-eight years with an average of thirty-one years.
      The vascular malformation was located in the occipital lobe or under the temporal
      lobe. Its main blood supply was from the basilar artery. Headache and hemorrhage
      were common clinical manifestations. Some cases had a defect of the visual field.
      Vertebral angiography is necessary for diagnosis of this disease. All the
      seventeen cases were operated without any death. The operative approach and
      experience in seeking for the vascular malformation during the operation are
      discussed.

PMID- 8288214
TI  - [Relationship between location and nipple discharge of breast cancer and its
      clinical significance].
AB  - The relationship between the location and the discharge of breast cancers in 50
      cases was analyzed from May 1980 to May 1989. Those lesions were located beneath
      the areolae or near the areolae. Ductograms and cytology were very useful in the
      diagnosis. Most of them (72.7% and 69.2% respectively) belonged stage I. Five
      year survival was 100% and 92.6% respectively. But those located far away from
      areola tended to become bigger and bigger, and invaded the large ducts. So the
      nipple discharge appeared. Most of them (69.2%) were in stage III. Five-year
      survival was 52.8%. The prognosis of this group was poorer than that of the
      former group.

PMID- 8288215
TI  - [Preconcentration of trace Fe, Mn, Cu and Cd in water with charcoal and
      determination by flame atomic absorption spectroscopy].
AB  - The absorption of Fe, Mn, Cu and Cd by charcoal and the influence of pH, particle
      size and temperature on absorption were studied. A method for the
      preconcentration of these irons in water was established, and with flame atomic
      absorption spectroscopy a content as low as microgram/L could be determined. The
      recovery and the coefficient of variance (n = 6) were in the range of 90-113% and
      2.6-9.9%, respectively. The proposed method is simple, rapid, accurate
      reproducible and suitable for the preconcentration and determination of titled
      metal irons in different kinds of water.

PMID- 8288216
TI  - [A simplified technique for decerebrating rats].
AB  - A simple and effective technique is described for decerebration of rat. The brain
      tissue at the precollicular level was gently and slowly aspirated. The two cut
      surfaces of the brainstem were covered with small pieces of gelfoam sponge or
      cotton balls soaked in thrombin solution. No ligation or clamp of the common
      carotid arteries of their branches was performed. After decerebration with this
      technique, the respiration rate, the heart rate and the mean femoral arterial
      pressure of the animals were stable for more than 10 hours. Successful
      intracellular recordings and labelings of medullary respiratory neurons were
      obtained from this type of preparation of rat. The technique for decerebrating
      rats described here may be used for acute experiments in which brainstem
      regulatory functions are investigated.

PMID- 8288217
TI  - [Capillary blood viscosimeter of the microcomputer].
AB  - On the basis of specific property of non-Newtonian fluid (blood) we have worked
      out the formula of capillary blood viscosimeter:sheat stress tau alpha = alpha
      rho gh/2L shear rate f (tau alpha) = 1/pi alpha 3 [3q + h(dq/dh)] and designed
      and produced the prototype. Repetition experiments have indicated that the
      property of the instrument is stable, and a comparison of the prototype with the
      cone and plate viscosimeter has demonstrated the reliability of the measurements.

PMID- 8288218
TI  - Identification, chromosomal location, and genome organization of mammalian G
      protein-coupled receptors.
AB  - Vertebrate G-protein-coupled receptors are encoded by a diverse multigene family.
      Thirteen distinct G-protein-coupled receptors (Gpcr) were cloned from mouse
      germline cDNA following amplification in the polymerase chain reaction (PCR) with
      degenerate oligonucleotide primers complementary to the third and sixth
      transmembrane domains. Eleven Gpcr clones were mapped to single sites in the
      mouse genome following interspecific backcross analysis. One clone was mapped to
      two sites and another was not polymorphic in the cross and could not be mapped.
      Gpcr loci were well dispersed throughout the mouse genome and mapped to
      chromosomes 1, 2, 3, 4, 5, 8, 9, 10, 13, 17, and 18. Six Gpcr clones likely
      represent mouse homologs of already identified receptors, one Gpcr clone may
      identify a third type of IL-8 receptor, and three Gpcr clones appear to encode
      novel G-protein-coupled receptors. Further, three factor crosses and Southern
      blot analyses demonstrated that Gpcr16 maps proximally within the Spr deletion on
      mouse chromosome 1, near the Vil and Bcg loci. Human chromosomal locations for
      most Gpcr loci could be predicted based on linkage homologies that have been
      identified between human and mouse. Mapping additional G-protein-coupled
      receptors against the panel of murine interspecific backcrosses should expand our
      understanding of mammalian Gpcr gene evolution and genome organization.

PMID- 8288219
TI  - Cloning of the cDNA (DSC1) coding for human type 1 desmocollin and its assignment
      to chromosome 18.
AB  - Desmosomes are adhesive epithelial junctions that contain two distinct classes of
      cadherin-related glycoproteins (desmogleins and desmocollins), both of which
      occur as several different isoforms whose expression is related to epithelial
      differentiation. We have now isolated cDNA clones encoding a human desmocollin
      that is expressed in the more differentiated layers of human epidermis. This
      isoform has 53% amino acid identity with the previously isolated human (type 3)
      desmocollin, which is expressed in the basal layers of the epidermis. However,
      the N- and C-termini of the mature proteins are more highly conserved. Using a
      panel of somatic cell hybrids, human type 1 desmocollin (gene DSC1) has been
      assigned to chromosome 18, the same location as the other desmocollin gene (DSC3)
      and the three desmoglein (DSG) genes already mapped.

PMID- 8288220
TI  - DNA sequence analysis of human chromosome 21 notI linking clones.
AB  - Portions of 16 chromosome 21 NotI linking clones were sequenced. These linking
      clone sequences represent sequence-tagged restriction sites that are potentially
      useful for finding genes and for finer genome mapping and sequencing. All of the
      clones were G+C rich (54 to 83%). CpG and GpC dinucleotide frequencies were very
      close to the expected values based on base composition and were very similar in
      15 of the clones. Most of the NotI linking clones were derived from CpG islands,
      which are often associated with genes. Five NotI linking clones had a high
      potential for coding regions; 7 additional clones may also contain coding
      regions. The NotI linking clones had many short homologous regions, but no
      extensive homologies either with each other or with GenBank sequences.

PMID- 8288221
TI  - Linkage mapping of the human thromboxane A2 receptor (TBXA2R) to chromosome
      19p13.3 using transcribed 3' untranslated DNA sequence polymorphisms.
AB  - The actions of thromboxane A2 as a prostaglandin mediator are dependent on its
      recently cloned and sequenced receptor. The identification and characterization
      of DNA polymorphisms in the thromboxane A2 receptor (TBXA2R) will advance the
      study of this gene as a candidate in a number of medical disorders. We amplified
      a 573-nucleotide fragment of the transcribed 3' untranslated region of the TBXA2R
      gene using the polymerase chain reaction (PCR) and the published cDNA sequence.
      This region was found to contain two sequence polymorphisms within an Alu. These
      DNA polymorphisms were demonstrated using an efficient method of direct solid
      phase sequence analysis. Three of the four expected alleles were observed in the
      CEPH families. TBXA2R was localized to chromosome 19 by PCR amplification in a
      series of monochoromosomal human/rodent somatic cell hybrids. Linkage mapping
      places TBXA2R closest to the anonymous marker D19S120, with a maximal LOD =
      19.55, at a theta = 0.05 in the CEPH panel of DNAs. Multipoint linkage analysis
      places TBXA2R between the markers D19S120 and PMS207 on the telomeric end of
      chromosome 19p13.3.

PMID- 8288222
TI  - Molecular characterization of the murine neural retina leucine zipper gene, Nrl.
AB  - The NRL gene (D14S46E) is expressed in cells of human retina and encodes a
      putative DNA-binding protein of the leucine zipper family. Here we describe the
      analysis of the murine homolog of the NRL gene, Nrl. Various cDNAs resulting from
      alternate polyadenylation are characterized. The deduced polypeptide sequence is
      highly conserved between mouse and human, with an identical basic motif and
      leucine zipper domain. The nucleotide sequences in the 5' and 3'-untranslated
      regions also show significant homology. The 3'-untranslated region contains a
      polymorphic AGG-trinucleotide repeat. The murine Nrl gene consists of three
      exons; of these, the first is untranslated. The 5'-upstream promoter region has
      no canonical TATA box, but contains consensus binding site sequences for several
      DNA-binding proteins. Analysis of RNA from adult mouse tissues confirms the
      retina-specific expression of Nrl. This study provides the basis for dissecting
      the cis-regulatory elements involved in the retina-specific expression and for
      the development of an experimental model to investigate the function or any
      diseases associated with this gene in humans.

PMID- 8288223
TI  - ZNF75: isolation of a cDNA clone of the KRAB zinc finger gene subfamily mapped in
      YACs 1 Mb telomeric of HPRT.
AB  - We have previously mapped a zinc finger genomic motif (ZNF75) to the Xq26
      cytogenetic band by using a hybrid panel. Here, we report the isolation of the
      transcribed counterpart in a cDNA clone and its further localization. The cDNA
      clone, from a lung fibroblast library, is assembled from three exons, including a
      289 amino acid (AA) long open reading frame containing a recently described
      motif, the Kruppel-associated box, 42 AA long, in exon 2. By comparison with
      other reported members of the subfamily, the exon-intron boundaries also appear
      to be very well conserved. Further analysis allowed us to map this gene 1 Mb
      downstream from the HPRT gene in the published YAC contig that extends across
      Xq26. Two other motifs, 87 and 78% homologous to ZNF75 at the amino acid level,
      were identified by PCR on total human DNA, but map outside Xq24-qter.

PMID- 8288224
TI  - Cloning and comparative mapping of a human chromosome 4-specific alpha satellite
      DNA sequence.
AB  - We have isolated and characterized two human alphoid DNA clones: p4n1/4 and
      pZ4.1. Clone p4n1/4 identifies specifically the centromeric region of chromosome
      4; pZ4.1 recognizes a subset of alphoid DNA shared by chromosomes 4 and 9. The
      specificity was determined using fluorescence in situ hybridization experiments
      on metaphase spreads and Southern blotting analysis of human-hamster somatic cell
      hybrids. The genomic organization of both subsets was also investigated.
      Comparative mapping on chimpanzee and gorilla chromosomes was performed. p4n1/4
      hybridizes to chimpanzee chromosomes 11 and 13, homologs of human chromosomes 9
      and 2q, respectively. On gorilla metaphase spreads, p4n1/4 hybridizes exclusively
      to the centromeric region of chromosome 19, partially homologous to human
      chromosome 17. No hybridization signal was detected on chromosome 3 of both
      chimpanzee and gorilla, in both species homolog of human chromosome 4. Identical
      comparative mapping results were obtained using pZ4.1 probe, although the latter
      recognizes an alphoid subset distinct from the one recognized by p4n1/4. The
      implications of these results in the evolution of centromeric regions of primate
      chromosomes are discussed.

PMID- 8288225
TI  - Correction of mucolipidosis III in vitro by gene transfer.
AB  - Mucolipidosis II (ML II, I-cell disease) and mucolipidosis III (ML III, pseudo
      Hurler polydystrophy) are human autosomal recessive genetic disorders resulting
      from deficient UDP-N-acetylglucosamine:lysosomal enzyme precursor N
      acetylglucosamine-1-phosphotransferase (GNPT) activity. Normally, this enzyme is
      involved in the processing of most lysosomal enzymes. Cultured fibroblasts from
      individuals with either disorder are deficient in a broad array of lysosomal
      enzymes as a result of the diminished GNPT activity. We report the correction of
      this phenotype by fusing transformed ML III cells generated for this study to
      lethally irradiated rodent cells. This method of gene transfer does not require
      selection for the gene of interest, animal models, nor any knowledge of the gene
      product except a screening method for its presence. It has generated corrected
      cell hybrids that contain approximately 1% hamster-derived sequences. These cell
      lines, which contain the hamster analogue to the human phosphotransferase gene,
      are useful for the molecular cloning of the gene defective in ML II and ML III.

PMID- 8288226
TI  - Structure and localization of the gene encoding human peripheral myelin protein 2
      (PMP2).
AB  - Peripheral myelin protein 2 (PMP2) is a small, basic, and cytoplasmic lipid
      binding protein of peripheral myelin. In this paper, we describe the cloning,
      characterization, and chromosomal mapping of the human PMP2 gene. The gene is
      about 8 kb long and consists of four exons. All exon-intron junction sequences
      conform to the GT/AG rule. The 5'-flanking region of the gene has a TA-rich
      element (TATA-like box) and a single defined transcription initiation site
      detected by the primer extension method. The gene for human PMP2 was assigned to
      chromosome 8q21.3-q22.1 by spot hybridization of flow-sorted human chromosomes
      and fluorescence in situ hybridization.

PMID- 8288227
TI  - Molecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene
      (WNT5A) to chromosome 3p14-p21.
AB  - The highly conserved Wnt genes belong to a widely distributed family of
      presumptive signaling molecules that have been implicated not only in the
      regulation of normal pattern formation during embryogenesis and differentiation
      of cell lineages, but also in oncogenic events. All of the known vertebrate Wnt
      genes encode for 38- to 43-kDa cysteine-rich putative glycoproteins, which have
      features typical of secreted growth factors: a hydrophobic signal sequence, a
      conserved asparagine-linked oligosaccharide consensus sequence, and 22 conserved
      cysteine residues whose relative spacing is maintained. In this study, we report
      the cloning and sequencing of several overlapping cDNAs encoding approximately
      4.1 kb of the human homologue of Wnt-5A. The mature protein contained 343
      residues (M(r) approximately 38,000 excluding any post-translational
      modifications) with a > 93% homology to the reported sequences of other Wnt-5A
      proteins (> 99% homologous to mouse Wnt-5A). This protein maintained certain
      features--a hydrophobic signal sequence, the Wnt-1 family "signature sequence"
      (CKCHGvSGSC), and a number of other conserved amino acid residues: 24 cysteine
      residues, 4 asparagine-linked oligosaccharide consensus sequences, and a tyrosine
      sulfation site--that have been found in all other Wnt-5A proteins. Reverse
      transcriptase PCR analysis of RNA from a variety of human embryonic, neonatal,
      and adult cells and/or tissues showed that human Wnt-5A expression was detected
      only in neonatal heart and lung. It may be relevant, however, that the 3'
      untranslated region contained numerous AT-rich motifs that could be involved in
      the rapid degradation of mRNA. Finally, using a combination of Southern blotting,
      PCR amplification, and in situ hybridization, the human Wnt-5A (WNT5A) gene was
      mapped to chromosome 3p14-p21.

PMID- 8288228
TI  - Genomic distribution and transcription of solitary HERV-K LTRs.
AB  - The human genome contains a family of endogenous retroviruses, HERV-K, with
      sequence homology to the B-type mouse mammary tumor virus. We have now identified
      a single HERV-K LTR within the C-type-related human retroviral element S71. The
      HERV-K LTR is located in the antisense direction between the S71 gag and the pol
      gene, replacing the 5' half of S71 pol. A number of HERV-K LTR-related cDNA
      clones were detected by screening various human cDNA libraries with an S71 HERV-K
      LTR probe, indicating abundant transcription of HERV-K-related LTRs in human
      tissues. Sequence analysis of four cDNA clones revealed LTR sequences with a
      nucleotide identity of 70 to 90% with HERV-K10 LTR. Some HERV-K-related LTR
      sequences contain potential short open reading frames. The analyzed cDNA clones
      do not harbor any retroviral sequences other than those related to HERV-K LTRs.
      However, most of the solitary LTRs were found to be coexpressed with cellular
      sequences. Transcription of these LTRs is probably directed by external cellular
      promoters. We show that HERV-KLTR-like sequences entered the primate genome about
      33-40 million years ago. We estimate the human genome to contain about 25,000
      copies of HERV-K-related LTRs, which are distributed over most human chromosomes
      in an irregular manner.

PMID- 8288229
TI  - Construction of a bovine genomic library of large yeast artificial chromosome
      clones.
AB  - We have constructed a yeast artificial chromosome (YAC) library derived from bull
      fibroblasts in primary culture. The library consists of 21,500 clones arranged on
      224 gridded plates (96 or 8 x 12 positions) and in 2 x 224 96-well microplates
      maintained as permanent frozen stocks. An average insert size of 750 kb was
      estimated from the analysis of 200 randomly selected YACs, giving a sixfold
      coverage of the bovine genome for the total library. A screening strategy based
      on the polymerase chain reaction that allows the identification of individual
      clones has been devised. Screening of the library with six locus-specific markers
      of interest led to the isolation of 34 positive clones. The proportion of
      chimeric YACs was estimated from the analysis of a subset of the positive clones:
      3 of 9 YACs were found to contain noncontiguous DNA.

PMID- 8288230
TI  - Linkage map of nine loci defined by polymorphic DNA markers assigned to rat
      chromosome 13.
AB  - A genetic map of nine loci defined by polymorphic DNA markers was created using a
      single cross of F344/N and LEW/N rats. The markers contained polymorphic simple
      sequence repeats identified in five genes, renin (Ren), cardiac troponin T
      (Tnnt3), synaptotagmin (Syt2), Na+,K(+)-ATPase catalytic subunit (Atp1a2), and
      the Asp-, Gly-, Glu-, and Leu-tRNA gene cluster (Trnegl), as well as four
      anonymous DNA segments. Analysis of the segregation of the alleles of these
      markers in F2 intercross progeny of F344/N and LEW/N rats indicated the following
      locus order and distances between pairs of loci: D13N1-5 cM-Ren-1 cM-Tntt3-0 cM
      Syt2-12 cM-D13N2-25 cM-Atp1a2-0 cM-Trnegl-7 cM-D13N3-4 cM-D13N4. Three of the
      loci, Ren, Trnegl, and Atp1a2, have previously been assigned to rat chromosome
      13. Except for Ren, none of the loci have previously been mapped by linkage
      analysis. The markers for these loci were characterized in a total of 13 inbred
      rat strains (F344/N, LEW/N, LOU/MN, WBB1/N, WBB2/N, MR/N, MNR/N, ACI/N, SHR/N,
      WKY/N, BN/SsN, BUF/N, and LER/N) and were found to be highly polymorphic, with
      two to eight alleles detected for each marker. These markers expand the genetic
      map of the rat and should be valuable tools for future genetic studies. An
      examination of human and mouse comparative map information for all loci assigned
      to rat chromosome 13 shows significant synteny conservation with the q arm of
      human chromosome 1 and the distal portion of mouse chromosome 1.

PMID- 8288231
TI  - Efficient construction of high-resolution physical maps from yeast artificial
      chromosomes using radiation hybrids: inner product mapping.
AB  - For the positional cloning of genes and other novel types of genetic experiments,
      in humans and other organisms, there is a crucial need for techniques with which
      genome-wide high-resolution ordered clone maps can be rapidly constructed.
      Current best methods, such as sequence-tagged site (STS) content mapping, entail
      a large number of experiments and, in practice, require large low-resolution
      yeast artificial chromosome (YAC) clones and very many STSs. In this paper, we
      introduce a new approach, inner product mapping (IPM), that overcomes these
      limitations. IPM uses radiation hybrids (RHs) to provide localizing signatures
      for YACs. Two independent data tables that compare YACs against RHs and RHs
      against STSs are obtained; these tables are combined to produce a computed map of
      the YACs against ordered STSs. IPM maps each YAC independently, requires
      relatively few RH comparisons to map a YAC, and can work with small (or large)
      YACs and few (or many) STSs. This paper describes IPM and presents computer
      simulations supporting the efficiency of IPM over that of competing methods.

PMID- 8288232
TI  - Localization of a gene responsible for nonspecific mental retardation (MRX9) to
      the pericentromeric region of the X chromosome.
AB  - Nonspecific X-linked mental retardation (MRX) includes several distinct entities
      with mental retardation but without additional distinguishing features. The MRX
      family reported here has been classified previously as MRX9. In this study, we
      performed linkage analysis of MRX9 with a panel of 43 polymorphic DNA markers
      dispersed over chromosome X. Two-point linkage analysis revealed lod scores of
      3.52 and 3.82 at 0% recombination for OATL1 and MAOA, both located in Xp11.2
      p11.4. Lod scores for linkage with PGK1P1, DXS106, and DXS132, all located in
      Xq11-q13, were 3.83, 3.82, and 3.52, respectively, all at 0% recombination.
      Multipoint linkage analysis showed two peaks with MAOA and DXS132/DXS106,
      respectively. Analysis of recombinational events indicated a position of the MRX9
      gene between DXS164 and DXS453. These findings are compatible with a location of
      the MRX9 gene in the pericentromeric region of the X chromosome at Xp21-q13.

PMID- 8288233
TI  - Linkage mapping of 40 randomly isolated liver cDNA clones in the mouse.
AB  - We report the chromosomal mapping of 43 loci for 40 randomly isolated mouse liver
      cDNA clones by linkage analysis in an interspecific backcross of ((C57BL/6J x Mus
      spretus) x C57BL/6J). The clones were sequenced from both sides and a subset was
      examined for expression in various mouse tissues. Fifteen of the 40 mapped cDNA
      clones are either identical or strongly related to known sequences in GenBank,
      while 25 represent new genes. Additional loci mapped in this cross include 53
      simple sequence repeat polymorphisms and 40 restriction fragment length variants
      from previously characterized cDNA markers. Nine homologous human genes were
      identified for 7 mouse liver cDNA clones. One clone that maps to mouse chromosome
      3 (D3Ucla1) identified a novel homologous segment (synteny) on human chromosome
      18q23 (D18S372E). These studies provide linkage mapping and initial
      characterization of random cDNA clones that may provide a resource for the
      positional candidate cloning of disease genes.

PMID- 8288234
TI  - Localization of the gene encoding peptidylglycine alpha-amidating monooxygenase
      (PAM) to human chromosome 5q14-5q21.
AB  - Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is a
      multifunctional protein containing two enzymes that act sequentially to catalyze
      the alpha-amidation of neuroendocrine peptides. Southern blot analysis of human
      placental DNA demonstrated that PAM is encoded by a single gene. The chromosomal
      localization of the PAM gene was established using in situ hybridization. A 2.2
      kb human PAM cDNA hybridized to human metaphase chromosomes revealed a
      significant clustering of silver grains over chromosome 5 bands q14-q21. The gene
      encoding another enzyme important in the post-translational processing of
      neuroendocrine precursors, prohormone convertase 1 (PC1), is localized in the
      same region (5q15-q21).

PMID- 8288235
TI  - Paucity of novel short interspersed repetitive element (SINE) families in human
      DNA and isolation of a novel MER repeat.
AB  - An extensive compilation of renaturation rate data for human DNA is presented as
      an empirical guide for genomic hybridization studies and to document as
      accurately as possible the repetitive sequence content of the human genome.
      Approximately 15% of the genome renatures with heterogeneous rates characteristic
      of moderately repetitive sequences. Cross hybridization studies of this fraction
      with known repetitive sequences show that it is largely composed of known
      moderately repetitive sequences and contaminating highly repetitive sequences.
      These findings limit the maximum possible abundance of unidentified families of
      short interspersed elements (SINEs) in human DNA. Exhaustive analysis by
      subtractive hybridization of a small library constructed from short fragments of
      repetitive sequences yields few additional new SINEs, again suggesting the
      limited abundance of such sequences.

PMID- 8288237
TI  - Absence of myotonic dystrophy protein kinase (DMPK) mRNA as a result of a triplet
      repeat expansion in myotonic dystrophy.
AB  - Myotonic dystrophy is an autosomally dominant inherited disease in which system
      wide abnormalities are caused by a triplet repeat expansion within the 3'
      untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. To
      determine the effect an expanded repeat region has on DMPK expression, we have
      separated the chromosome 19 homologues from a 36-year-old woman with myotonic
      dystrophy into different cell lines by way of somatic cell hybridization. Hybrid
      DM9101 contains the normal DMPK allele (13 repeats), whereas hybrid DM1115
      harbors the mutant allele (approximately 133 repeats). Reverse
      transcription/polymerase chain reaction (RT/PCR) amplification of coding
      sequences from the DMPK gene has shown both reduced levels of primary DMPK
      transcripts and impaired processing of these transcripts in hybrid cell line
      DM1115. These findings suggest that the presence of a large number of repeats in
      the 3' untranslated region of the DMPK gene reduces both the synthesis and the
      processing of DMPK mRNA, resulting in undetectable levels of processed DMPK mRNA
      from the mutant allele.

PMID- 8288236
TI  - A microsatellite-based multipoint index map of human chromosome 22.
AB  - Utilizing the CEPH (Centre d'Etude du Polymorphism Humain) reference panel and
      genotyping data for 24 simple tandem repeat polymorphism (STRP) markers, we have
      constructed a 15-locus multipoint genetic framework map of human chromosome 22.
      The markers form a continuous linkage group of 51 cM in males and 81 cM in
      females. Likely genetic locations are provided for 9 additional STRP sequences.
      The map was constructed employing the CRIMAP computational methodology to build
      the multipoint map via a stepwise algorithm. The quality of the framework map was
      evaluated using a battery of statistical diagnostics that suggest a typing error
      frequency of 0.1% for markers within the map.

PMID- 8288238
TI  - Genomic organization of the porcine skeletal muscle ryanodine receptor (RYR1)
      gene coding region 4624 to 7929.
AB  - Excitation-contraction coupling in skeletal muscle is mediated by two calcium
      channels located in the membranes of the transverse tubule and the sarcoplasmic
      reticulum. Calcium is released from the terminal cisternae of the sarcoplasmic
      reticulum via the ryanodine receptor. Abnormal increases in myoplasmic free
      calcium caused by a defect in the ryanodine receptor have been reported in
      malignant hyperthermia. Malignant hyperthermia is a life-threatening
      pharmacogenetic disorder in a variety of species and is triggered by volatile
      anesthetics and depolarizing muscle relaxants. To study the genomic organization
      of the porcine skeletal muscle ryanodine receptor gene, we have isolated six
      genomic fragments spanning approximately 80 kb of chromosomal DNA. In this
      report, we describe the genomic organization of a 15.5-kb genomic fragment
      comprising 18 exons coding for region 4624 to 7929 of the porcine skeletal muscle
      ryanodine receptor gene.

PMID- 8288239
TI  - Molecular cloning of the cDNA encoding a human renal sodium phosphate transport
      protein and its assignment to chromosome 6p21.3-p23.
AB  - Resorption of phosphate by the kidney is an important function in the maintenance
      of phosphate homeostasis in mammals, and a defect in renal phosphate uptake has
      been implicated in at least three human genetic disorders. We have isolated a
      cDNA encoding a human sodium-dependent phosphate transport protein (NPT1). This
      cDNA hybridizes to a single 2.5-kb RNA transcript from human kidney cortex, its
      nucleotide sequence shows 80.3% identity to the rabbit NaPi-1 sequence, and it
      encodes a polypeptide of 467 amino acids. Amino acid sequence comparisons
      indicate a 69.7% identity between human NPT1 and rabbit NaPi-1 polypeptides; the
      inclusion of conservative substitutions increases the homology between the two
      proteins to 81.5%. Alignment of both sequences also reveals several conserved
      potential N-glycosylation and protein kinase C phosphorylation sites. Polypeptide
      hydropathy analysis predicts several membrane-spanning domains. This cDNA maps
      the location of the gene encoding NPT1 to human chromosome 6q21.3-p23.

PMID- 8288240
TI  - Molecular diversity of the SCG10/stathmin gene family in the mouse.
AB  - SCG10 is a neuronal growth-associated protein that shares an amino acid sequence
      similarity with an 18- to 19-kDa phosphoprotein named stathmin (also called p19,
      p18, Op18, pp17, prosolin, pp20, 19K, and leukemia-associated phosphoprotein,
      Lap18), which is more broadly expressed in a variety of cell types of the neural,
      immune, and reproductive systems. The sequence similarity has suggested that
      SCG10 and stathmin have been derived from structurally and evolutionarily related
      genes. To explore the structural and evolutionary relationships between these
      genes, we have isolated a series of cosmid and phage clones that covers the
      entire region of the mouse stathmin gene and most of the mouse SCG10 gene. The
      SCG10 transcription unit spans at least 30 kb, while the stathmin gene is 6 kb in
      length. Both genes consist of five exons, and many of the intron/exon boundaries
      fall into the homologous regions of conserved domains of these two proteins.
      However, the promoter-proximal regions are distinct in the two genes, suggesting
      that they have evolved by fusion of the duplicated coding exons to unique
      promoters. Southern blot analysis indicates that SCG10 mRNA is encoded by a
      single gene in the mouse genome, while stathmin cDNA probes detect multiple
      genes. Chromosome mapping experiments reveal that the SCG10 gene is localized at
      the proximal region of mouse chromosome 3 and is linked to Il-7, while the
      stathmin gene loci are distributed to three chromosomes; the authentic stathmin
      gene lies on chromosome 4, whereas the loci on chromosomes 9 and 17 are likely to
      be pseudogenes. These data are consistent with the idea that the neuron-specific
      SCG10 gene evolved by duplication and modification of the more broadly expressed
      stathmin/Lap18 gene.

PMID- 8288241
TI  - Characterization of the mouse haptoglobin gene.
AB  - Plasmids containing mouse cDNA encoding haptoglobin, a major plasma protein that
      binds free hemoglobin, have been isolated and characterized. The amino acid
      sequence predicted by the mouse haptoglobin cDNA was 80% identical to human
      haptoglobin and 90% identical to rat haptoglobin sequence. The mouse haptoglobin
      probe was used to demonstrate a single haptoglobin gene in the genome of C57BL6
      mice mapped to chromosome 8. Sequence analysis of the mouse Hp gene promoter
      revealed two unique features: the presence of a second TATA box with a 48-bp
      trinucleotide repeat immediately upstream. The enhancer element and the sequences
      shown to be required for cytokine and hormonal regulation of the rat Hp gene are
      highly conserved in mouse. Interestingly, the single nucleotide variation G to A,
      which completely inactivates the IL-6 responsive element A in the rat Hp gene, is
      identical in mouse. This suggests that the presence of an inactive IL-6
      responsive element A in Hp genes is common in rodents.

PMID- 8288242
TI  - Comparative high-resolution mapping of human and primate chromosomes by
      fluorescence in situ hybridization.
AB  - A molecular cytogenetic approach that facilitates high-resolution comparative
      mapping of defined human genes in different primate species is presented.
      Fluorescence in situ hybridization and digital imaging microscopy were used to
      visualize human DNA probes on simultaneously banded or "painted" metaphase
      chromosomes of great apes (Pan troglodytes, Gorilla gorilla, Pongo pygmaeus),
      hylobatids (Hylobates lar and Hylobates syndactylus), and Old World monkeys
      (Macaca fuscata and Cercopithecus aethiops). Using a series of DNA probes,
      chromosomal rearrangements in the karyotypes of primates were readily detected at
      the molecular cytogenetic level. This approach should contribute considerably to
      the understanding of primate phylogeny and evolution.

PMID- 8288243
TI  - A novel missense mutation in the gene for lipoprotein lipase resulting in a
      highly conservative amino acid substitution (Asp180-->Glu) causes familial
      chylomicronemia (type I hyperlipoproteinemia).
AB  - A previously undescribed single missense mutation (C-->G) was detected within
      exon 5 of the LPL gene in two members of an Italian family affected with type I
      hyperlipoproteinemia. This mutation causes a highly conservative amino acid
      replacement (Asp-->Glu) at position 180 of the mature LPL protein resulting in a
      virtual absence of LPL enzyme activity and LPL enzyme mass in postheparin plasma.
      Adipose tissue mRNA concentrations and mRNA sizes were not affected. Both
      patients were homozygous for the mutation, whereas the parents were heterozygous.
      Comparison of the expression of the mutated cDNA and the wildtype cDNA in cos-7
      cells revealed proper transcription and translation of the mutated clone into an
      immunologically detectable protein. The mutated LPL protein was secreted from the
      cells in a manner similar to that of wild-type LPL and bound to heparin-Sepharose
      with identical properties. However, the mutated enzyme, in contrast to wildtype
      LPL, exhibited no detectable lipolytic activity against a triglyceride substrate.
      Our results demonstrate that even a highly conservative amino acid replacement
      outside the proposed active site of LPL is incompatible with proper enzyme
      function.

PMID- 8288244
TI  - Characterization of the NTRK1 genomic region involved in chromosomal
      rearrangements generating TRK oncogenes.
AB  - TRK oncogenes are created by chromosomal rearrangements linking the tyrosine
      kinase domain of the NTRK1 gene (encoding one of the receptors for the nerve
      growth factor) to foreign activating sequences. TRK oncogenes are frequently
      detected in human papillary thyroid carcinoma, as result of rearrangements
      involving at least three different activating genes. We have found that the
      rearrangements creating all the TRK oncogenes so far characterized fall within a
      2.9-kb XbaI/SmaI restriction fragment of the NTRK1 gene. Here we report the
      nucleotide sequence and the exon organization of this fragment.

PMID- 8288245
TI  - The human granzyme A (HFSP, CTLA3) gene maps to 5q11-q12 and defines a new locus
      of the serine protease superfamily.
AB  - Human granzyme A (HFSP, Hanukah factor serine protease; CTLA3, cytotoxic T
      lymphocyte-associated serine esterase-3), a homodimeric, trypsin-like serine
      protease of 60 kDa found in granules of cytolytic T cells and natural killer
      cells, is implicated in lymphocyte-mediated target cell lysis. It contributes to
      DNA fragmentation in perforin (PRF1)-lysed target cells through an unknown
      mechanism. We have isolated a cosmid clone for the functional gene of human
      granzyme A and established its complete exon-intron map of 10 kb. Using an 11-kb
      subfragment of the cloned genomic DNA as a probe, we have identified the
      chromosomal position of human granzyme A on 5q11-q12. Thus, the human granzyme A
      gene falls into a region of homology between human chromosome 5 and mouse
      chromosome 13, band D, where the mouse granzyme A gene has been located
      previously. The granzyme A gene is not linked to known members of the large
      superfamily of serine proteases.

PMID- 8288246
TI  - Assignment of the human RT6 gene to 11q13 by PCR screening of somatic cell
      hybrids and in situ hybridization.
AB  - RT6 is a T cell membrane protein that has attracted interest because a defect in
      RT6 expression is associated with susceptibility to autoimmune type I diabetes in
      DP-BB rats and NOD mice. Using PCR screening of human/rodent somatic cell hybrids
      and fluorescence in situ hybridization, we have determined that the gene for the
      human RT6 homologue is located at 11q13, centromeric to the gene for tyrosinase
      (TYR, albino locus) and telomeric to that for fibroblast growth factor 4 (FGF4).
      The data suggest that the human RT6 gene constitutes a new linkage group with TYR
      and the gene for olfactory marker protein (OMP) on 11q, which has a counterpart
      in mouse chromosome 7. Thus, in the human, the RT6 locus is dissociated from the
      hemoglobin beta chain locus (HBB) and its neighboring conserved linkage group at
      11p15, in contrast to the mouse, in which RT6 shows a tighter linkage to Hbb than
      to Tyr. The results support the conclusion that there has been considerable
      intrachromosomal reshuffling of linked genes since the divergence of primates and
      rodents.

PMID- 8288247
TI  - The murine homologue of the human interleukin-8 receptor type B maps near the Ity
      Lsh-Bcg disease resistance locus.
AB  - Interleukin-8 (IL-8), a member of the chemokine alpha subfamily, is a
      chemoattractant for neutrophils. Cell surface receptors for IL-8 have been cloned
      from rabbits and humans. Two related but different IL-8 receptors (IL-8R) have
      been characterized from humans. IL-8RA and IL-8RB bind IL-8 at high affinity but
      IL-8RB also binds GRO/MGSA and NAP-2 at high affinity. Using the human IL-8RB
      cDNA as a probe, we have determined that the homologous murine gene maps near the
      Ity-Lsh-Bcg disease resistance locus. A murine homologue of the human IL-8RB was
      isolated from a genomic library. This gene would encode a protein of 359 amino
      acids and would have a 68 and 71% amino acid identity with human IL-8RA and IL
      8RB, respectively. Additional mapping data using the murine gene revealed the
      following genetic distances (in cM +/- 1 standard error) from the centromere:
      Mylf--7.9 +/- 2.7--Lsh-Ity-Bcg--1.9 +/- 1.4--Il8rb--1.9 +/- 1.4--Vil-- 5.9 +/-
      2.3--Acrg--2.9 +/- 1.7--Bcl-2.

PMID- 8288248
TI  - Cloning of the human dopamine D5 receptor gene and identification of a highly
      polymorphic microsatellite for the DRD5 locus that shows tight linkage to the
      chromosome 4p reference marker RAF1P1.
AB  - We identified a cosmid clone with exact sequence homology to part of the human
      dopamine D5 receptor gene (DRD5) after screening a cosmid library with the human
      DRD1 gene. The dopamine D5 receptor was mapped to chromosome 4p15.1-p15.3 by in
      situ hybridization and using a somatic cell hybrid panel. We report here the
      further localization of the DRD5 gene following identification of a highly
      polymorphic dinucleotide repeat sequence in the cosmid clone. The microsatellite
      (D5(CT/GT/GA)n) had 12 alleles with a polymorphic information content value of
      0.77. Linkage analysis in 39 CEPH pedigrees demonstrated tight linkage to the
      chromosome 4p reference marker RAF1P1 (Zmaxf 20.66 at theta f 0.05 and ZmaxM
      16.57 at theta m 0.07).

PMID- 8288249
TI  - Assignment of the phosducin (PDC) gene to human chromosome 1q25-1q32.1 by somatic
      cell hybridization and in situ hybridization.
AB  - Phosducin is a soluble photoreceptor phosphoprotein that probably modulates
      phototransduction in the retina and thus qualifies as a potential candidate gene
      for retinitis pigmentosa. Using both human/mouse somatic cell hybrids and in situ
      hybridization to human metaphase chromosomes, we have mapped this gene to
      chromosome 1q25-1q32.1.

PMID- 8288250
TI  - Refined mapping of the GM2 activator protein (GM2A) locus to 5q31.3-q33.1, distal
      to the spinal muscular atrophy locus.
AB  - The GM2 activator locus (GM2A) had previously been considered as a candidate gene
      for some forms of spinal muscular atrophy (SMA; mapped to 5q11.2-q13.3). It was
      eliminated as a possible candidate because PCR-based mapping failed to localize
      the gene to chromosome 5, as was previously reported using an ELISA-based
      methodology. However, we demonstrated that the PCR primers used preferentially
      amplified a processed pseudogene (GM2AP) that we mapped to chromosome 3 and that
      GM2A was located on chromosome 5. In this report, we reconsider the candidacy of
      GM2A by refining its localization on chromosome 5 using fluorescence in situ
      hybridization. We localize GM2A to 5q31.3-q33.1; thus, it is not a candidate gene
      for SMA.

PMID- 8288251
TI  - Chromosomal localization of the human gene encoding the 51-kDa subunit of
      mitochondrial complex I (NDUFV1) to 11q13.
AB  - The 51-kDa flavoprotein subunit of mitochondrial NADH:ubiquinone oxidoreductase
      (Complex I) [NADH dehydrogenase (ubiquinone), flavoprotein 1 (51 kDa); EC
      1.6.5.3] plays an important role in the formation of the NADH-binding site and is
      believed to be the principal site of entry for electrons donated by NADH into the
      respiratory chain. Human cDNA fragments of the 51-kDa protein were generated by
      polymerase chain reaction and used to localize the gene (NDUFV1) for this subunit
      to 11q13 by two separate techniques. This region of the human genome is strongly
      implicated in a number of different forms of cancer.

PMID- 8288252
TI  - Mapping of the phenol sulfotransferase gene (STP) to human chromosome 16p12.1
      p11.2 and to mouse chromosome 7.
AB  - We have recently cloned a cDNA encoding the human phenol-preferring phenol
      sulfotransferase (P-PST) enzyme. An oligonucleotide primer pair based on the
      human STP (representing sulfotransferase, phenol-preferring) cDNA sequence was
      synthesized and was employed in polymerase chain reaction (PCR) amplification of
      human genomic DNA to identify a 525-bp DNA fragment. The DNA sequence of this
      portion of the STP gene, near the 5' end of the coding region, was determined.
      The amplified genomic fragment contained two small introns of 104 and 89 bp. When
      DNA samples from a human-hamster somatic cell hybrid panel were screened by PCR
      using these primers, only those hybrids that contained human chromosome 16 were
      positive for the 525-bp genomic fragment. To identify the specific region on
      chromosome 16 that contained the STP gene, PCR amplification reactions were
      performed on a human-mouse somatic cell hybrid panel containing defined portions
      of human chromosome 16. The results indicated that STP is localized proximal to
      the gene for protein kinase C, beta 1 polypeptide (PRKCB1), in the region from
      the distal portion of 16p11.2 to p12.1. The human STP gene maps near the locus
      for Batten disease (CLN3). Furthermore, we have determined by genotyping of
      murine interspecific backcross progeny that the homologous gene in mouse (Stp)
      localizes to the syntenic region of mouse chromosome 7 near the D7Mit8 (at 54 cM)
      and D7Bir1 markers.

PMID- 8288253
TI  - X-linked ocular albinism and sensorineural deafness: linkage to Xp22.3.
AB  - X-linked ocular albinism with late-onset sensorineural deafness (OASD) is an
      autonomous disorder that poses significant clinical problems, causing affected
      individuals to be blind and deaf by early middle age. Classical X-linked ocular
      albinism (without deafness; OA1) has recently been linked to markers in the
      Xp22.2-Xp22.3 region of the human genome. In the present report, a large South
      African family with OASD was investigated at the molecular level and tight
      linkage was found to the DXS452 locus at Xp22.3 using 25 informative meioses,
      with a maximum lod score of 7.1 at a recombination fraction of 0.00. These
      findings suggest that OA1 and OASD are allelic variants or that they may be due
      to contiguous gene defects.

PMID- 8288254
TI  - Refinement of the localization of the gene for human intraacrosomal protein SP-10
      (ACRV1) to the junction of bands q23-->q24 of chromosome 11 by nonisotopic in
      situ hybridization.
AB  - The human sperm antigen SP-10 is a testis-specific protein associated with the
      matrix of the acrosomal vesicle in developing spermatids and the acrosomal matrix
      and membranes of ejaculated sperm. A previous study, utilizing somatic cell
      hybrids, localized the gene for SP-10 to chromosome 11 and assigned the gene
      symbol ACRV1 (acrosomal vesicle protein-1). Although previous analysis of several
      somatic cell hybrids containing portions of chromosome 11 indicated that ACRV1
      was in the p12-->q13 region, the present fluorescence in situ hybridization
      studies using cDNA, ribo, and genomic versions of probes for SP-10 coupled to
      analysis of an expanded series of somatic cell hybrids demonstrated the refined
      localization of ACRV1 to the junction of bands q23 and q24 of chromosome 11. A
      comparison of the three types of probes used for the in situ study demonstrated
      that while the genomic probe hybridized most efficiently, the riboprobe
      hybridized to the same location and was superior to the cDNA probe in mapping
      this single-copy gene. This report emphasizes the utility of riboprobes for
      chromosome localization of single-copy genes.

PMID- 8288255
TI  - Mouse models of Niemann-Pick disease: mutation analysis and chromosomal mapping
      rule out the type A and B forms.

PMID- 8288256
TI  - Assignment of an intron-containing human heat-shock protein gene (hsp90 beta,
      HSPCB) to chromosome 6 near TCTE1 (6p21) and two intronless pseudogenes to
      chromosomes 4 and 15 by polymerase chain reaction amplification from a panel of
      hybrid cell lines.

PMID- 8288257
TI  - Mapping the human melanocortin 2 receptor (adrenocorticotropic hormone receptor;
      ACTHR) gene (MC2R) to the small arm of chromosome 18 (18p11.21-pter).

PMID- 8288258
TI  - Assignment of the gene for the core protein II (UQCRC2) subunit of the
      mitochondrial cytochrome bc1 complex to human chromosome 16p12.

PMID- 8288259
TI  - The gene for human phosducin (PDC), a soluble protein that binds G-protein beta
      gamma dimers, maps to 1q25-q31.1.

PMID- 8288260
TI  - Mapping the Hrc gene to proximal mouse chromosome 7: delineation of a conserved
      linkage group with human 19q.

PMID- 8288261
TI  - Human RSU1 is highly homologous to mouse Rsu-1 and localizes to human chromosome
      10.

PMID- 8288262
TI  - Additional evidence for a gene locus for progressive cone dystrophy with late rod
      involvement in Xp21.1-p11.3.

PMID- 8288263
TI  - Adequacy of single-locus approximations for linkage analyses of oligogenic
      traits: extension to multigenerational pedigree structures.
AB  - When a disease is controlled by two or more mendelian loci acting epistatically,
      it can be modeled in a linkage analysis as a single-locus mendelian disease with
      reduced penetrance. Previous work has demonstrated the reliability of such
      approximation for nuclear families, but not for extended pedigrees. We simulated
      extended pedigrees under two-locus models, in which one of the two disease loci
      was linked to a marker, and analyzed them both under the correct two-locus models
      and under single-locus approximations. The single-locus approximations provided
      results that were very close to the correct two-locus results. This held true,
      whether we ascertained pedigrees based on the presence of at least one affected
      individual, or based on the presence of at least five affected individuals. While
      a simulation study cannot guarantee that extrapolation of the results to models
      other than those examined is justified, our findings strongly suggest that single
      locus linkage analysis can be reliably used in analyzing two-locus disorders in
      extended pedigrees. We also found striking confirmation of the importance of
      performing linkage analyses under both dominant and recessive models when the
      mode of inheritance is unknown, for extended pedigrees ascertained through
      multiple affected individuals.

PMID- 8288264
TI  - Transferrin types, iron-binding capacity and body iron stores.
AB  - Increased body iron stores and transferrin (TF) variants have been found to be
      associated with adverse health effects believed to be caused by oxygen free
      radicals. Previous attempts to establish a relationship between TF types, serum
      TF concentrations and iron-binding have been inconclusive. We have studied serum
      iron, total iron-binding capacity (TIBC), TF saturation and serum ferritin in
      relation to genetic TF types in a population sample (691 females and 639 males)
      from northern Sweden in an attempt to elucidate whether individuals with TF
      variants associated with adverse somatic and reproductive effects (TFC2 and C3)
      have increased body iron stores. As expected there was a highly significant sex
      difference, males manifesting increased body iron stores viz. increased levels of
      serum iron, TF saturation and serum ferritin, and a lower TIBC. There was no
      consistent and statistically significant association between the TFC2 variant and
      the parameters that indicate iron binding and storage. Thus the associations
      between TFC2 and somatic and reproductive damage appear to be independent of iron
      binding and body iron stores. TIBC (and TF levels) showed significant differences
      between TF types in females (p = 0.0015) but not in males. In females the TFC3
      variant was associated with a significantly lower (p = 0.002) TIBC value. This
      decreased TIBC value was, however, not accompanied by an increased ferritin
      value, thus there was no unequivocal evidence for an association between TFC3 and
      increased body iron stores.

PMID- 8288265
TI  - Chromosomal mapping of two members of the human glutamate dehydrogenase (GLUD)
      gene family to chromosomes 10q22.3-q23 and Xq22-q23.
AB  - Glutamate dehydrogenase (GLUD) is an important mitochondrial enzyme that
      participates in neuronal transmission by catalyzing the deamination of L
      glutamate, which serves as a potent excitatory neurotransmitter. The direct
      involvement of GLUD in the pathogenesis of certain human neurodegenerative
      disorders has been suggested recently. To investigate its possible role in the
      induction and progression of these disorders, we have initiated studies focusing
      on the chromosomal organization of the several members of the GLUD family and
      their functional status. In the present study using a panel of human x rodent
      somatic cell hybrids and in situ hybridization to metaphase chromosomes, we
      documented that the members of the GLUD gene family are dispersed in the human
      genome. The functional GLUD1 gene was mapped to chromosome 10q22.3-q23, and an
      intronless processed gene (GLUDP1) to chromosome Xq22-q23, while the truncated
      intron-containing GLUD pseudogene GLUDP2 was also assigned on chromosome 10, but
      not closely linked to the GLUD1 gene. These results provide novel information
      concerning the chromosomal organization of the human GLUD gene family.

PMID- 8288266
TI  - Serum complement (C3, BF, C4) types in Swedish Saamis.
AB  - Serum complement (C3, BF, C4) types were examined in Swedish Saamis (Lapps). In
      agreement with previous studies, a very low frequency of the C3*F allele (0.033)
      was found. Compared to Swedes and other Caucasian populations, Swedish Saamis
      showed a significantly increased frequency of the BFS, C4A4 and C4B2 variants,
      and a lower frequency of C4 deficiency. BFS, C4A4 and C4B2 show haplotype
      associations and thus the frequency of the S-A4-B2 complotype is significantly
      increased among the Saamis. Although the serum complement constitution of the
      Saamis shows some similarity with that of Asiatic Mongoloid populations it is
      unlikely to be due to Asiatic ethnic influence. The marked genetic deviations of
      the Saamis from all other populations has often been interpreted as a result of
      the founder effect and genetic drift. In this particular case, however,
      immunogenetic adaptation appears to be a plausible alternative explanation for
      the deviations in genetic complement factors.

PMID- 8288267
TI  - ABO and rhesus blood groups and adverse outcomes of pregnancy.
AB  - Interview and medical-record data of 11,659 nondiabetic, non-asthmatic women were
      analyzed to evaluate the relationship between ABO and Rh blood groups and adverse
      outcomes of pregnancy. No statistically significant associations were found in
      logistic regression analyses that controlled for age, race, smoking and parity.
      The results of our study demonstrate the importance of controlling for
      confounding variables, and do not support a relationship between maternal blood
      group and adverse pregnancy outcomes including malformations.

PMID- 8288268
TI  - Preaxial polydactyly and other defects associated with Klippel-Feil anomaly.
AB  - A 5-year-old girl with Klippel-Feil anomaly and bimanual polydactyly of
      triphalangeal thumb is described. The main findings include--in addition to the
      classical congenital fusion of cervical vertebrae and the clinical triad of short
      neck, limitation of head and neck movement and low-set posterior hairline-
      several associated abnormalities: scoliosis, spina bifida occulta, absence of
      ribs, conductive hearing loss, mirror movements, unilateral renal ectopia with
      dilation of the collecting system, and microtia. The hand malformation appears to
      represent a previously unreported defect associated with Klippel-Feil anomaly.

PMID- 8288269
TI  - Elicitation of a predominantly lambda light chain-bearing antibody response in
      BALB/c mice to a novel bifunctional aminocarboxylate chelating agent.
AB  - A panel of murine monoclonal antibodies has been raised against the
      aminocarboxylate bifunctional chelating agent PA-DOTA complexed with Samarium.
      Ninety percent of the antibodies (43 of 48) used a lambda light chain. The
      binding specificity of 11 of the antibodies was examined by competition assays
      using several structurally related aminocarboxylate chelating agents containing
      different metals. Most of the antibodies are directed against the macrocycle ring
      of PA-DOTA and require the presence of a metal within the structure for binding.

PMID- 8288270
TI  - Immunologic and biochemical analysis of TNT-1 and TNT-2 monoclonal antibody
      binding to histones.
AB  - Two novel murine monoclonal antibodies that bind to intracellular antigens,
      designated TNT-1 and TNT-2, have been generated by immunizing mice with nuclear
      extracts from human lymphoma cells. The monoclonal antibodies were initially
      identified by indirect immunofluorescence on lymphoma cell lines and subsequently
      were found to stain the nucleus of all cell types from several species including
      plants by indirect immunofluorescence techniques. Immunoblot analysis
      demonstrated that TNT-1 bound to a protein of 22 kD and TNT-2 bound to two
      proteins of 15 and 22 kD, consistent with the known molecular weight of histones.
      To characterize their immunoreactivity, competition radioimmunoassays were
      performed using purified histone fractions H1, H2a, H2b and H3. By these assays,
      TNT-1 was found to bind to histone fraction H1 and TNT-2 to an epitope common to
      histone fractions H1 and H3. Histones are found in abundance in the nucleus of
      the cell and are known to play a major role in chromosome structure and gene
      expression. Upon cell death, histones remain tightly bound to DNA and
      consequently provide an abundant intracellular antigen that can be exploited in
      targeting necrotic cells, such as those found in tumors.

PMID- 8288271
TI  - Neutralization of tetanus toxin by human monoclonal antibodies directed against
      tetanus toxin fragment C.
AB  - Two hybridomas (designated 143 and 147) producing human monoclonal antibodies
      (IgG1) directed against tetanus toxin were established by fusion of Epstein-Barr
      virus transformed human peripheral B lymphocytes with the heteromyeloma SPAM-8.
      The hybridomas produced antibodies in concentrations of approx. 3.5 micrograms/ml
      (hybridoma 143) and 6.4 micrograms/ml (hybridoma 147) using conventional flask
      cultures and 33.9 micrograms/ml and 36.2 micrograms/ml, respectively, in dialysis
      cultures. The antibodies were shown to react with tetanus toxin, toxoid and
      fragment C in ELISA, and reactivity with tetanus toxin and fragment C was
      confirmed in SDS-polyacrylamide gel electrophoresis followed by Western blots.
      The antibody binding sites were located to two different epitopes of fragment C
      as shown in a competition assay using biotinylated antibodies. Furthermore,
      binding of both antibodies to fragment C was inhibited by the addition of the
      receptor-associated ganglioside GT1b. Neutralization of tetanus toxin in
      concentrations equivalent to 100-120 IU per mg of antibody was observed for both
      antibodies in a mouse protection assay.

PMID- 8288272
TI  - Monoclonal antibodies against the plant cytokinin, cis-zeatin riboside.
AB  - Three monoclonal antibodies (two IgG1 and one IgA) prepared against the plant
      cytokinin, cis-zeatin riboside, were characterized for use in a fluorescence
      competition enzyme linked immunosorbant assay (F-ELISA). Immunoassays that
      employed each antibody detected femtomole quantities of the homologous cytokinin
      and characteristic quantities of structurally-related cytokinins. One of the
      antibodies was used to quantify HPLC-purified cis-zeatin riboside recovered from
      spiked samples of wheat leaves. These are the first monoclonal antibodies against
      a cis- derivative of a plant cytokinin and will be useful for purification and
      quantification of cis-zeatin and the 9-riboside and 9-glucoside in plant samples.

PMID- 8288273
TI  - Monoclonal antibodies that recognize trypsin binding domain of human urinary
      trypsin inhibitor.
AB  - Three MAb M2, B6, P1 (IgG1 type) against human urinary trypsin inhibitor (UTI), a
      glycoprotein with antiinflammatory properties, have been produced by
      hybridization of mouse myeloma cells P3o1 with spleen cells of immunized mice
      BALB/c. Competitive ELISA-examination of peroxidase conjugates of M2, B6, and P1
      MAb in the presence of the trypsin binding domain shows the highest affinity of
      M2 antibody for this domain. On the basis of MAb M2 competitive ELISA of UTI
      concentration in urine is proposed. ELISA detectable changes in the UTI content
      of urine from patients with nephritis without renal failure can be considered as
      an early index of renal parenchyma damage.

PMID- 8288274
TI  - Differential DNA damage detected in hybridomas.
AB  - Monoclonal antibody technology has improved over recent years. However, there
      remains a serious problem with regard to the stability and antibody production of
      the hybrid cell lines. In order to investigate the potential increased
      sensitivity of hybridomas to DNA damage, we produced a monoclonal antibody
      producing cell line in our laboratory. Three types of cells were analyzed by the
      single cell gel technique to determine single strand DNA damage, including the
      fusion partner FO, BALB/c splenocytes and an IgM producing hybridoma. The
      hybridoma cell line displayed a statistically significant increase in sensitivity
      to induced DNA damage as compared to the fusion partners used in its
      establishment. The instability of hybridomas in culture may be associated with
      their inherent increased susceptibility to DNA damage.

PMID- 8288275
TI  - A stochastic network model of the interaction between cardiac rhythm and
      artificial pacemaker.
AB  - The electrical interaction between the heart and an artificial pacemaker is often
      complex. Because of the sophistication and diversity of dual-chamber device
      algorithms, even experienced cardiologists can have difficulty interpreting paced
      electrocardiograms (ECG's). In order to study heart-pacemaker interaction (HPI),
      a computer model of the cardiac conduction system has been developed which
      includes the effects of artificial pacemaker function and failure. The stochastic
      network model of cardiac conduction consists of five vertices, each representing
      a functional electrophysiologic element. Electrophysiologic multidimensional
      conditional probability functions determine the depolarization status of each
      vertex. The atrioventricular (AV) node is emulated using a mathematical model
      which includes the influence of past cycle lengths on AV nodal conduction time.
      Twenty-three classes of arrhythmias may be simulated and, for pacing simulation,
      one of 12 antibradycardia pacing modes may be chosen. Random effects of pacemaker
      malfunction including oversensing, undersensing, or failure-to-capture may be
      simulated through the use of probability distribution functions. This model
      should prove useful in the development of pacemaker algorithms, determining
      patient-specific pacemaker therapy, and predicting causes for apparent pacemaker
      malfunction. The model has been used in the development of an expert system to
      analyze paced ECG's for pacemaker function and malfunction.

PMID- 8288276
TI  - Sampling theory for neuromagnetic detector arrays.
AB  - The sampling theorem for wave-number-limited multivariable functions is applied
      to the problem of neuromagnetic field mapping. The wave-number spectrum and other
      relevant properties of these fields are estimated. A theory is derived for
      reconstructing neuromagnetic fields from measurements using sensor arrays which
      sample either the field component Bz perpendicular to the planar grid of
      measurement points, or the two components delta Bz/delta x and delta Bz/delta y
      of its gradient in the xy plane. The maximum sensor spacing consistent with a
      unique reconstruction is determined for both cases. It is shown that, when two
      orthogonal components of the gradient are measured at every site of the
      measurement grid, the density of these sensor-pair units can be reduced, without
      risk of aliasing, to half of what is necessary for single-channel sensors in an
      array sampling Bz alone. Thus the planar and axial gradiometer arrays are
      equivalent in the sampling sense provided that the number of independent
      measurements per unit area is equal.

PMID- 8288277
TI  - Nonlinear analysis of the hippocampal subfields of CA1 and the dentate gyrus.
AB  - The paper discusses the use of nonlinear bispectral analysis in examining the
      hippocampal EEG collected at subfields of CA1 and the dentate gyrus during the
      vigilance state of REM sleep. The cross-bispectrum and its unique capabilities of
      detecting and quantifying quadratic nonlinear interactions occurring between
      these two hippocampal subfields are explained and demonstrated with simulation
      examples and EEG data. It was found in this study that quadratic nonlinear
      interactions exist between CA1 and the dentate gyrus in the 6-8 frequency band
      which dominates the theta (theta) rhythm observed in the hippocampal EEG during
      REM sleep. As a result, energy components around the frequency band of the second
      order harmonics of theta rhythm are not totally spontaneous, but generated
      largely due to quadratic nonlinear interactions.

PMID- 8288278
TI  - ECG compression using long-term prediction.
AB  - A new algorithm for ECG signal compression is introduced. The compression system
      is based on the subautoregression (SAR) model, known also as the long-term
      prediction (LTP) model. The "periodicity" of the ECG signal is employed in order
      to further reduce redundancy, thus yielding high compression ratios. The
      suggested algorithm was evaluated using an in-house database. Very low bit rates
      on the order of 70 b/s are achieved with a relatively low reconstruction error
      (percent rms difference-PRD) of less than 10%. The algorithm was compared, using
      the same database, with the conventional linear prediction (short-term prediction
      -STP) method, and was found superior at any bit rate. The suggested algorithm can
      be considered a generalization of the recently published average beat subtraction
      method.

PMID- 8288279
TI  - A feedback control system for real-time formant estimation. I--Static and dynamic
      analysis for sinusoidal input signals.
AB  - This paper presents a novel analog scheme suitable for the real-time estimation
      of formant frequencies. Formant tracking is based on a feedback technique which
      uses both the amplitude and phase characteristics of two stagger-tuned bandpass
      filters to give an improved dynamic behavior. The implementation of the system
      requires a small number of components, and is practical for low-power
      applications. An analysis of the static and dynamic behavior is given for
      sinusoidal input signals. The transient response is independent of the amplitude
      level of the input signal. The system is designed for second formant detection in
      a cochlear prosthesis system.

PMID- 8288280
TI  - A feedback control system for real-time formant estimation. II--Analysis of a
      hysteresis effect and F2 estimation.
AB  - This paper presents the second part of the analysis of a feedback control system
      for real-time formant estimation. The system behavior is analyzed for an input
      signal composed of two sinusoids. If the frequency difference between the two
      input spectral lines is sufficiently great and the amplitude ratio is within
      certain limits, a hysteresis effect occurs. Then the system shows a tendency to
      select one of the two input spectral lines. The existence of the second line has
      only little influence on the accuracy of the detection of the selected line. From
      the analysis, conclusions of the system behavior regarding formant estimation can
      be drawn. A design example for second formant detection is simulated and compared
      with the results obtained by simulation of a zero-crossing system for F2
      estimation and LPC analysis.

PMID- 8288281
TI  - The response of a spherical heart to a uniform electric field: a bidomain
      analysis of cardiac stimulation.
AB  - A mathematical model describing electrical stimulation of the heart is developed,
      in which a uniform electric field is applied to a spherical shell of cardiac
      tissue. The electrical properties of the tissue are characterized using the
      bidomain model. Analytical expressions for the induced transmembrane potential
      are derived for the cases of equal anisotropy ratios in the intracellular and
      interstitial (extracellular) spaces, and no transverse coupling between fibers.
      Numerical calculations of the transmembrane potential are also performed using
      realistic electrical conductivities. The model illustrates several mechanisms for
      polarization of the cell membrane, which can be divided into two categories,
      depending on if they polarize fibers at the heart surface only or if they
      polarize fibers both at the surface and within the bulk of the tissue. The latter
      mechanisms can be classified further according to whether they originate from
      continuous or discrete properties of cardiac tissue. If cardiac tissue had equal
      anisotropy ratios, a large membrane polarization would be induced at the heart
      surface that would become negligible a few length constants into the tissue. If
      cardiac tissue were continuous and had no transverse coupling between fibers, a
      membrane polarization would be induced throughout the bulk that would arise from
      an "activating function" similar to the one used to describe neural stimulation.
      Polarization would occur if the fibers were curving, if the cross-sectional area
      of the tissue were changing (fiber branching), or both. The numerically
      calculated transmembrane potential is intermediate between those predicted using
      the assumptions of equal anisotropy ratios and no transverse coupling between
      fibers. Although discrete properties of cardiac tissue are not incorporated into
      this model, an estimate of their effect indicates that the amplitude of the
      polarization caused by the resistance of the cellular junctions is similar to
      that caused by fiber curvature and branching. The spatial distribution of the
      polarization, however, is quite different.

PMID- 8288282
TI  - Frequency domain dipole localization: extensions of the method and applications
      to auditory and visual evoked potentials.
AB  - We describe a statistical frequency domain approach to localizing equivalent
      dipole generators of human brain evoked potentials. The frequency domain
      representation allows considerable data reduction, constrains the magnitude
      function of the dipoles to be smooth, and accounts for the statistical properties
      of the background EEG. A previous paper described a restrictive model in which
      the dipole orientations were assumed to be fixed over time, and only one dipole
      was allowed. In this paper, we consider the more general model in which the
      orientation can vary over time, and which includes multiple dipole generators.
      The varying orientation model has the practical advantage of being more nearly
      linear and more flexible than the fixed orientation model, which facilitates
      convergence of the iterative fitting algorithm. We suggest a measure of goodness
      of-fit that compares the likelihood of the dipole model with the likelihoods of
      saturated and null models. We report the results of fitting the model to recorded
      auditory and visual evoked potentials. A single dipole with fixed orientation
      seems to be an adequate model of the auditory midlatency response, while two
      dipoles with varying orientation are needed to fit the later P200 component.
      Analysis of the visual P100 response to unilateral stimulation localized a
      generator in the contralateral occipital cortex, as expected from anatomical
      considerations. A two-dipole model fit the visual P100 response of bilateral
      stimulations, and the locations of the two dipoles were similar to the locations
      obtained by single-dipole fits to the responses to left and right unilateral
      stimuli.

PMID- 8288283
TI  - Relationship between dipole parameter estimation errors and measurement
      conditions in magnetoencephalography.
AB  - The relationship between dipole parameter estimation errors and measurement
      conditions in magnetoencephalography is determined by computer simulation. The
      model uses a single current dipole in a spherical homogeneous medium. Dipole
      parameters are estimated using a moving dipole procedure. Signal-to-noise ratio
      (SNR) is defined as the square-root of the ratio of the average signal power to
      the average noise power over all measurement points. At SNR > 20, accurate
      estimation can be carried out independently of dipole depth and coil size. At SNR
      < 20, dipole depth influences estimation error. When the dipole is located near
      the center of the sphere, the measurement region should include both extrema of
      the magnetic field to minimize estimation error. However, when the dipole is not
      so deep, the position of the measurement region does not influence estimation
      error. When SNR < 4, estimation error increases as coil size increases. Coil size
      minimizing estimation error is determined by the ratio of environmental magnetic
      field noise to electrical noise. For a constant size of measurement region,
      increasing the number of measurement points decreases estimation error to a
      certain level. This error level depends on SNR. The number of measurement points
      required to minimize estimation error also depends on SNR.

PMID- 8288284
TI  - SAR distributions in interstitial microwave antenna arrays with a single dipole
      displacement.
AB  - The use of interstitial microwave antenna array hyperthermia (IMAAH) as a
      treatment for cancer, in conjunction with radiation therapy and chemotherapy, has
      been investigated widely. The heating pattern produced by a coherently phased 915
      MHz asymmetric antenna array displays the maximum power deposition in the array
      center. This paper investigates the effect of variable insertion depth between
      antennas of an array on the heating patterns produced. The "study" of this
      heating behavior demonstrates a similar effect to that of the variably phased
      arrays, showing a shift of the heating peak towards the periphery of the tumor,
      offering a more simple method for the clinical treatment of such tumors.

PMID- 8288285
TI  - Finite element computations of specific absorption rates in anatomically
      conforming full-body models for hyperthermia treatment analysis.
AB  - Finite element techniques for three-dimensional specific absorption rate (SAR)
      computation in anatomically based human models are presented. The formulations
      center on Helmholtz weak forms which have been shown to be numerically robust and
      to afford additional sparsity in the resulting system of algebraic equations.
      Practical solution of these equations depends critically on the realization of an
      effective sparse matrix solver. Experience with several conjugate gradient-type
      methods is reported. The findings show that convergence rate (and even
      convergence in some cases) degrades significantly with increasing matrix rank and
      decreasing electrical loss for mesh spacings which adequately resolve the
      physical wavelengths of the electromagnetic wave propagation. However, with
      proper choice of algorithm and preconditioning, reliable convergence has been
      achieved for matrix ranks exceeding 2 x 10(5) on domains having sizeable volumes
      of electrically lossless regions. An automatic grid generation scheme for
      constructing meshes which consist of variable element sizes that conform to a
      predefined set of boundaries is discussed. Example meshes of homogeneous and
      heterogeneous human anatomies, the boundaries of which have been derived from CT
      scan information, are shown. These results highlight the fact that 3D finite
      element mesh generation remains a difficult problem, but usable meshes with this
      level of complexity can be generated. Integration of the finite element
      formulation, the sparse matrix solver, and the mesh generation scheme is shown to
      lead to algorithms that can be implemented on inexpensive reduced instruction set
      computer (RISC) workstations with run times on the order of hours. An example of
      hyperthermia device simulation is presented which suggests that the finite
      element method is a practical alternative that rivals the impressive finite
      difference time-domain (FDTD) computations that have appeared.

PMID- 8288286
TI  - Analysis and optimization of waveguide multiapplicator hyperthermia systems.
AB  - A method is proposed for determining the excitation coefficients of an antenna
      array operating in a large rectangular waveguide and used as a hyperthermia
      system. The excitation coefficients of the array elements are optimized for
      attaining an improved specific absorption rate (SAR) distribution around a deep
      seated tumor. The method is applied to a two-dimensional problem of a piecewise
      homogeneous post in a waveguide representing a section of the human torso. The
      array is operating below the cutoff frequency of the dominant mode of the
      waveguide. Numerical simulations have been performed to check the effectiveness
      of this approach. The results show that by using the proposed optimization
      method, SAR distributions can be improved.

PMID- 8288287
TI  - Cyclic variation of the power of ultrasonic Doppler signals backscattered by
      polystyrene microspheres and porcine erythrocyte suspensions.
AB  - Factors affecting the power of the ultrasonic Doppler signal within the flow
      cycle have been evaluated experimentally using a pulsatile flow loop model.
      Polystyrene microspheres and porcine red cells suspended in saline solution for
      hematocrits between 2 and 40% were used as scattering fluid in the flow model.
      Experiments were performed at mean flow velocities of 11, 64, and 76 cm/s. In
      laminar flow experiments performed at a mean velocity of 11 cm/s, no variation of
      the Doppler power was found for both polystyrene microspheres and red cell
      suspensions (40% hematocrit). When turbulence was induced in the flow model, the
      power increased during systole, a maximum was observed early after peak systole,
      and a decrease was obtained in diastole during deceleration of flow. At higher
      mean flow velocities (64 and 76 cm/s), a significant cyclic variation of the
      Doppler power was also measured for all values of hematocrits (between 2 and
      40%). The power of the signal scattered by microspheres and red cell suspensions
      at 4% hematocrit dropped in systole, reached a minimum at peak systole, and then
      increased during early diastole. For red cells suspended in saline at 40%
      hematocrit, a slightly different pattern of variation was obtained. The cyclic
      variations observed at high flow velocities and in the presence of turbulence are
      believed to be associated with cyclic changes in the correlation among particles.
      In the present study, the effect of red cell aggregation on the cyclic variation
      has not been addressed.

PMID- 8288288
TI  - Development of a piezopolymer pressure sensor for a portable fetal heart rate
      monitor.
AB  - A piezopolymer pressure sensor has been developed for service in a portable fetal
      heart rate monitor, which will permit an expectant mother to perform the fetal
      nonstress test, a standard predelivery test, in her home. Several sensors are
      mounted in an array on a belt worn by the mother. The sensor design conforms to
      the distinctive features of the fetal heart tone, namely, the acoustic signature,
      frequency spectrum, signal amplitude, and localization. The components of a
      sensor serve to fulfill five functions: signal detection, acceleration
      cancellation, acoustical isolation, electrical shielding, and electrical
      isolation of the mother. A theoretical analysis of the sensor response yields a
      numerical value for the sensor sensitivity, which is compared to experiment in an
      in vitro sensor calibration. Finally, an in vivo test on patients within the last
      six weeks of term reveals that nonstress test recordings from the acoustic
      monitor compare well with those obtained from conventional ultrasound.

PMID- 8288289
TI  - On-line estimation of myoelectric signal spectral parameters and
      nonstationarities detection.
AB  - In this communication, we present a method for detecting nonstationarities of
      random time series with an approximately Gaussian distribution of amplitudes.
      This method is suitable for real time implementation. Here we report some results
      obtained by applying them to a time series of spectral parameters of surface
      myoelectric signals, collected during voluntary isometric contractions of human
      muscles. Moreover, we describe the computerized system that we used to implement
      our detector of nonstationarity. This system is based on the TMS 320C25 DSP chip
      and realizes on-line estimation and display of spectral parameters, as well as
      detection of their nonstationarities, featuring a sampling frequency up to 20 k
      samples/s. A friendly user interface, fully menu driven, allows the user to
      select different options during the system's operation by means of hot keys. The
      accuracy of the system was tested by comparing its estimates with those of an off
      line system, previously characterized, which we took as a reference. The
      estimates of spectral parameters obtained by means of the two systems were always
      consistent. The on-line stationarity detector was able to recognize rates of
      variation of the spectral parameters as small as 1%/s during contractions lasting
      10-15 s. This sensitivity makes it suitable for clinical application. The set of
      results herein presented has been selected to highlight the main characteristics
      of the system.

PMID- 8288290
TI  - Statistical discriminant analysis of arrhythmias using intracardial electrograms.
AB  - The problem of classifying ventricular arrhythmias from intracardial electrograms
      is considered. Standard statistical discrimination procedures are applied using a
      simple parametric model for the shape of the pulse near its peak. This approach
      makes simultaneous use of the model parameters, has well known statistical
      properties, and involves computations that can be carried out efficiently.
      Preliminary analyses of real data sets, using both linear and quadratic
      discrimination functions, yield promising results.

PMID- 8288291
TI  - An example of thermometry in volume by microwave radiometry.
AB  - We depict a method of determination of the size D depth z and temperature T0 +
      delta T of a cylindrical thermal structure embedded in an homogeneous glossy
      material, in the present case, water. A microwave radiometric image at 3 GHz
      points out the location of the thermal structure; its threshold provides the
      diameter D of the structure. The depth z derives from the ratio of the maximal
      radiometric intensities at 1.5 and 3 GHz. The combination of D,z and of the
      radiometric intensities gives delta T.

PMID- 8288292
TI  - Needed--a strong nursing position on preventive service.

PMID- 8288293
TI  - The phenomenology of knowing the patient.
AB  - Nurses' discourse about knowing the patient emerged as a recurring theme in an
      interpretive phenomenological study of the development of expertise in critical
      care nursing. The purpose of this article is to present analyses related to the
      meaning of knowing the patient, and its role in everyday nursing practice.
      Informants in the study were 130 nurses who practiced in adult, pediatric and
      newborn intensive care units of eight hospitals in three metropolitan areas. The
      data were group interviews in which nurses gave narrative accounts of exemplars
      from their practice; in addition, a sub-sample of 48 nurses were observed in
      their practice and participated in intensive personal history interviews. Knowing
      the patient means both knowing the patient's typical pattern of responses and
      knowing the patient as a person. Knowing the patient is central to skilled
      clinical judgment, requires involvement, and sets up the possibility for patient
      advocacy and for learning about patient populations.

PMID- 8288294
TI  - Tertiary nurse practitioners.
AB  - Tertiary nurse practitioners are proposed to meet the specialized health care
      needs of complex patients. Societal changes, increasing numbers of medically
      vulnerable people and increased costs of health care demand innovative responses
      to health care delivery. Nurse practitioners' effectiveness in primary care
      settings supports their introduction into acute care settings. Nurse
      practitioners are involved in tertiary care in response to a need for the
      delivery of care to patients with specialized needs. The evolution of the
      tertiary nurse practitioner role pre-dated the response of educational
      institutions to provide appropriate preparation for practitioners in tertiary
      care. Curricular imperatives and policy issues that will influence professional
      practice of the tertiary nurse practitioner are discussed.

PMID- 8288296
TI  - An emerging theory of human relatedness.
AB  - Theory of human relatedness addresses a pervasive human concern, establishing and
      maintaining relatedness to others, objects, environments, society and self. This
      theory, derived from a series of inductive and deductive strategies, views
      relatedness as a functional, behavioral system rooted in early attachment
      behaviors. Individuals move through different states of relatedness including
      connectedness, disconnectedness, parallelism and enmeshment. Social processes
      that contribute to this movement are sense of belonging, reciprocity, mutuality
      and synchrony. Disruptions in clients' relatedness contribute to biological,
      psychological, and social disturbances.

PMID- 8288295
TI  - Effect of nurse-client transaction on female adolescents' oral contraceptive
      adherence.
AB  - An experimental study was conducted to test the effect of a nurse-client
      transactional intervention (King, 1981) on 51 female adolescents' oral
      contraceptive adherence. Subjects were randomly assigned to a control or an
      experimental group. Both groups experienced the clinics' contraceptive teaching.
      Subjects in the experimental group experienced the transactional intervention.
      Contraceptive perceptions were measured immediately post-intervention and at the
      three-month follow-up. Oral contraceptive adherence was measured at the three
      month follow-up. Female adolescents who experienced the transactional
      intervention had greater levels of oral contraceptive adherence than those who
      had not (F = 4.15, p < .05).

PMID- 8288297
TI  - A place to be yourself: empowerment from the client's perspective.
AB  - This article describes a focused ethnography of a group of chronically mentally
      ill clients who were involved in a client-run drop-in center. Spradley's (1979)
      Developmental Research Sequence guided the research. Data were obtained from
      interviews, participant-observation and documents review. The qualitative
      analysis identified the major theme of empowerment, which had four process
      domains: participating, choosing, supporting and negotiating. These domains
      represented four levels of empowerment for this group. From the client's
      perspective, empowerment meant they participated more in the community, their
      choices were increased, they provided support for each other and they negotiated
      on a more equal basis with staff. A fifth domain, personal significance,
      described the effects of empowerment for each individual.

PMID- 8288298
TI  - Public health nurses' vision of their future reflects changing paradigms.
AB  - Health care over the past decade has undergone important changes that have
      implications for public health nursing. The focus of public health has expanded,
      as a result of the World Health Organization establishing the goal of "Health for
      All by the Year 2000," with its strategy of primary health care. To be active
      participants in this expansion, public health nurses must be more explicit about
      their current contributions to health care systems; develop nursing frameworks
      consistent with the systems' changing goals; and articulate their visions of the
      future. It is clear that the medical paradigm of health care services needs to
      change to one of primary health care. Based on results of a recent public health
      nursing research study, a conceptual framework for the future practice of public
      health nursing was developed.

PMID- 8288299
TI  - Positive mental attitude and health: what the public believes.
AB  - Content analysis was used with the responses of 167 people to open-ended
      questions regarding their understanding of the term "positive mental attitude"
      (PMA) and their beliefs about benefits and problems associated with PMA.
      Participants also responded to a scale which assessed their beliefs about the
      influence of PMA on illness onset and recovery. Analyses revealed wide diversity
      in understandings of the term, although a majority indicated that PMA means
      optimism or hope. The benefits of PMA included happiness, health and improved
      relationships. The problems included over-confidence and disappointment, but such
      problems were often said to be associated with over-enthusiastic use of PMA.
      Seventy-seven percent of the respondents agreed that PMA can prevent illness and
      94 percent agreed that PMA can aid in recovery from illness. Fewer agreed that
      PMA can prevent cancer or aid recovery from cancer.

PMID- 8288300
TI  - Childhood physical and sexual abuse: their relationship with depressive symptoms
      in adulthood.
AB  - The purposes of this study were to determine the prevalence of childhood physical
      and sexual abuse among 206 low-income single mothers and to examine the
      relationship of childhood abuse to current maternal depressive symptoms. Severe
      physical abuse was reported by 36 percent of the women. The prevalence of sexual
      abuse was 22 percent; more than one-half of these women were violently abused.
      High depressive symptoms were reported by 51 percent of the mothers. Both severe
      physical abuse and sexual abuse in childhood were associated with high depressive
      symptoms. Women who experienced violent sexual abuse were almost four and one
      half times more likely to report high depressive symptoms, compared to the women
      who were not sexually abused. These findings provide further evidence that
      childhood abuse may have long-term consequences for women's mental health.

PMID- 8288301
TI  - Physical health impairment and depression among older adults.
AB  - Factors were examined that contribute to depression among older adults, aged 60
      to 75 years. A convenience sample of 80 older adults living independently in the
      community was used. There were no differences found between participants with
      high or low physical impairment for demographic characteristics. Significant
      differences were found between the two groups for mastery, social resources and
      depression. Mastery, social resources and economic resources were significant
      predictors of depression. The findings support the empirical and theoretical
      links between stressful life events, specifically physical health impairment, and
      depression.

PMID- 8288302
TI  - Caregiver stress in grandparents raising grandchildren.
AB  - The purpose of this descriptive study was to examine caregiver stress in
      grandparents who are raising grandchildren as well as the antecedents to the
      child's placement with grandparents. The sample was 41 grandparents, aged 40 to
      78 years, with a mean of 55 years. Subjects reported increased psychological
      distress as measured by the Symptom Checklist-90-Revised inventory. Social
      isolation and restriction of role, as measured by the Parenting Stress Index,
      were found to be predictors of increased psychological distress. Child
      maltreatment, often involving parental substance abuse, was found to be the major
      antecedent to children being raised by grandparents.

PMID- 8288303
TI  - Preferences for decision-making autonomy.
AB  - Nurses' lack of autonomy has been identified as a leading cause of job
      dissatisfaction, but attempts to increase satisfaction by increasing autonomy
      have not always been successful. This survey of 356 randomly selected staff
      nurses and 130 head nurses from 16 hospitals extends previous work by identifying
      the preferred level of involvement in 21 patient care and 21 unit operation
      decisions. Staff nurses agreed on 60 percent of the decisions and, in general,
      preferred independent decision-making for patient care decisions and shared
      decision-making for unit operation. Head nurses indicated that staff nurses
      should have a higher level of autonomy than the staff nurses indicated for
      themselves.

PMID- 8288304
TI  - Reenactment interviewing: a methodology for phenomenological research.
AB  - Reenactment is proposed as an alternative interviewing strategy for
      phenomenological research. Three techniques borrowed from the psychodramatic
      method, warming up, scene-setting and soliloquy, are described as they were used
      in interviews with nurses participating in a study of caregiver/patient
      relationships. The rationale for and implementation of the techniques are
      discussed. Indications of successful reenactment during an interview are
      described and discussed. The data suggest that skillfully directed reenactment
      can generate intensely vivid recall of memories experiences and emotions,
      engendering rich descriptions of participants' lived experience and subsequently,
      produces significant dialogue between interviewer and participant. Parallels are
      drawn between phenomenological research/philosophy and the philosophy of action
      upon which psychodramatic techniques are based.

PMID- 8288305
TI  - Nursing as informed caring for the well-being of others.
AB  - Assumptions about four main phenomena of concern to nursing (persons/clients,
      health/well-being, environments and nursing) are presented and an elaboration is
      made of the structure of a theory of caring. The issues that arise when nursing
      is viewed as "informed caring for the well-being of others is also examined."

PMID- 8288306
TI  - Updating the nurses' bedside manner.

PMID- 8288307
TI  - Updating the nurses' bedside manner.

PMID- 8288308
TI  - Sleep inquiry: a look with fresh eyes.

PMID- 8288309
TI  - The statistical versus clinical significance debate.

PMID- 8288310
TI  - Distribution of Fc gamma receptors on trophoblast during human placental
      development: an immunohistochemical and immunoblotting study.
AB  - Expression of Fc gamma receptors on human placental trophoblast was investigated
      by immunostaining and immunoblotting using a panel of Fc gamma receptor
      monoclonal antibodies (mAb). Fc gamma receptors typical of other cell types were
      not detected on syncytiotrophoblast in term placentae when transplacental IgG
      transport was maximal. Unexpectedly, however, and by contrast with term, all Fc
      gamma receptor III mAb tested bound to first trimester placental
      syncytiotrophoblast by immunostaining. Reactivity was relatively restricted and
      varied between specimens. Fc gamma receptor III products of 41,000-45,000 and
      49,000-52,000 MW were consistently detected on first trimester trophoblast
      membranes by immunoblotting and levels of these products were greatly reduced
      following treatment with phosphatidylinositol-specific phospholipase C,
      suggesting that the early trophoblast Fc gamma receptor III is glycosyl
      phosphatidylinositol (GPI) linked. The mAb Leu-11b behaved differently to other
      anti-Fc gamma receptor III mAb examined. By immunostaining, Leu-11b bound to
      syncytiotrophoblast at term and detected both syncytiotrophoblast and underlying
      cytotrophoblast in the first trimester. In addition to the GPI-anchored Fc gamma
      receptor III in first trimester, Leu-11b also detected a 74,000 MW component on
      both first trimester and term trophoblast membranes by immunoblotting. Thus
      trophoblast appears to express a GPI-anchored Fc gamma receptor III in first
      trimester but not term placentae. With the exception of the 74,000 MW Leu-11b
      defined product whose function is unclear, currently available Fc gamma receptor
      mAb appear to be incapable of detecting the protein involved in IgG transport
      during the later stages of gestation.

PMID- 8288311
TI  - Effector mechanisms involved in cytokine-mediated bacteriostasis of Mycobacterium
      avium infections in murine macrophages.
AB  - In this study we found that addition of a range of doses of interferon-gamma (IFN
      gamma), tumour necrosis factor-alpha (TNF-alpha), or granulocyte-macrophage
      colony stimulating factor (GM-CSF) to cultures of bone marrow-derived murine
      macrophages infected with the 25291 strain of Mycobacterium avium gave rise to
      varying degrees of bacteriostasis. In contrast, similar treatment with
      interleukin-4 (IL-4) or IL-6 had no effect. However, when similar experiments
      with the former set of cytokines were performed using a panel of M. avium
      isolates, substantial isolate-to-isolate variation was observed. In cultures
      containing IFN-gamma, synthesis of substantial levels of reactive nitrogen
      intermediates was observed; however, neither these materials, nor reactive oxygen
      intermediates, were found to be responsible for observed bacteriostasis. In
      further experiments, in which the culture medium was supplemented with various
      concentrations of a weak acid or a weak base in order to influence the pH of
      macrophage intracellular compartments, it was found that the presence of the weak
      acid augmented the activity of IFN-gamma, whilst the weak base counteracted this
      effect. These data support the hypothesis, therefore, that the bacteriostatic
      effect of IFN-gamma against the growth of M. avium, rather than depending on
      reactive radical production, is mediated through acidification of the infected
      phagosome, perhaps through activation of proton pumps in the phagosomal membrane.

PMID- 8288312
TI  - Protein kinase C activation in human monocytes: regulation of PKC isoforms.
AB  - The distribution of protein kinase C (PKC) isoforms and phorbol 12-myristate 13
      acetate (PMA)-induced activation of PKC in human monocytes was investigated.
      Using Western blot analysis, PKC beta was found to be the most abundant isoform
      in monocytes. PKC beta was equally distributed in the cytosol and membrane. PKC
      alpha was readily detectable and found predominantly in the cytosol. Little to no
      PKC-epsilon, gamma, delta, and zeta were observed. Following the treatment of
      monocytes with PMA, the physical translocation of PKC alpha from the cytosol to
      the membrane occurred over 60 min. PMA-induced translocation of PKC-beta was
      difficult to detect by Western blot. Fura-2 analysis demonstrated that PMA
      induced PKC translocation was not accompanied by a net change in cytosolic
      calcium levels. Using histone as a substrate for PKC activity, an extremely rapid
      translocation of PKC-dependent histone phosphorylation (PKC-DHP) was induced by
      PMA. Cytosolic PKC-DHP activity decreased to undetectable levels within 8 min. In
      contrast, analysis of PKC-dependent endogenous substrate phosphorylation (PKC
      DESP) showed a pattern with a time-course similar to that observed with Western
      blot. Thus, translocation of PKC-DESP but not PKC-DHP activity correlated with
      PKC-alpha as determined by Western blot. The data support the concept that PKC
      activity is substrate dependent and suggest that using one assay for the
      measurement of PKC activity may lead to erroneous conclusions.

PMID- 8288313
TI  - Production of an early release, M(r) 36,000 monokine by stimulated rat
      macrophages.
AB  - Supernatants from rat peritoneal macrophage cultures stimulated with bacterial
      products contain a M(r) 36,000 factor that protects immature cortical thymocytes
      from loss of viability over a 4-hr incubation period in vitro. This effect could
      not be produced with purified transforming growth factor-beta or recombinant
      interleukin-6 (IL-6). Further, the partially purified M(r) 36,000 fraction was
      inactive in bioassays for IL-1 and tumour necrosis factor. Maximal production of
      the factor occurred 2 hr after the addition of 20 micrograms/ml of
      lipopolysaccharide, as assessed by the titre resulting in 100% protection of
      thymocytes in a viability assay. The detection of protective activity within 5
      min after addition of the stimulant could be attributed to the release of
      intracellular stores but protein synthesis was required to account for the
      increasing titre up to peak levels. The titre fell rapidly after 2 hr so that
      activity could not be detected at 4 hr. This profile of release was refractory to
      repeated stimulation with lipopolysaccharide. Conjoint addition of
      lipopolysaccharide and indomethacin, did, however, allow release in response to
      subsequent challenge. Related to this finding, prostaglandin E2 completely
      inhibited the release of protective activity.

PMID- 8288314
TI  - Detailed characterization of gamma delta T cells within the organs in mice:
      classification into three groups.
AB  - gamma delta T cells are known to localize preferentially in the epithelial
      regions and the hepatic sinusoids, and exhibit highly restricted V gene usage
      depending on their location. In the present study, gamma delta T cells in mice
      were further characterized in terms of their expression of the interleukin-2
      receptor beta-chain (IL-2R beta), CD4 and CD8, and CD8 alpha and beta. This
      experiment was arranged to investigate whether gamma delta T cells have different
      properties depending on the organs and how gamma delta T cells are different from
      extrathymic alpha beta T cells, i.e. alpha beta T cells in the liver and
      intraepithelial lymphocytes in the intestine, in terms of the above phenotypes.
      Three-colour immunofluorescence tests using monoclonal antibodies revealed that
      gamma delta T cells can be classified into three groups: gamma delta T cells of
      the liver type are all IL-2R beta+, are comprised of double-negative (DN) CD8-CD4
      and single-positive CD8+ (no CD4+) cells, and express CD8 alpha+ beta-; gamma
      delta T cells of the thymus type are a mixture of IL-2R beta+ and IL-2R beta-,
      are mainly DN, and express CD8 alpha+ beta+ if they carry CD8 antigens; and gamma
      delta T cells of the intestine type are also IL-2R beta+ or IL-2R beta-, are all
      CD8+, and express CD8 alpha+ beta-. gamma delta T cells in the spleen of normal
      mice are of the thymus type, while gamma delta T cells in the spleen of athymic
      nude mice seem to be of the liver type. All these properties of gamma delta T
      cells resemble those of extrathymic alpha beta T cells rather than regular alpha
      beta T cells of thymic origin. The present results reveal that gamma delta T
      cells and other extrathymic alpha beta T cells have many properties in common as
      primitive lymphocytes in phylogenetic development.

PMID- 8288315
TI  - Gamma delta T-cell lines isolated from intestinal epithelium respond to a B-cell
      lymphoma.
AB  - gamma delta T-cell hybrid clones were obtained from intestinal intraepithelial
      lymphocytes (i-IEL) by fusion with the BW5147 thymoma line. Four clones which
      expressed different V gamma/V delta genes were selected for further study. All of
      the gamma delta clones secreted interleukin-2 (IL-2) in the presence of the
      BALB/c-derived B-lymphoma line, A20. No alpha beta T-cell hybrid clones derived
      from spleen or i-IEL responded to A20. We obtained several pieces of evidence
      which strongly suggest that these responses are mediated by the gamma delta T
      cell receptor (TcR). Class II major histocompatibility complex (MHC), FcR and
      surface Ig expressed on A20 are not involved in the response. Native i-IEL
      derived from BALB/c selectively survive in culture in the presence of A20 cells.
      The ligand may be a superantigen-like molecule because all our gamma delta T-cell
      clones responded to A20 in spite of their different combinations of V gamma/V
      delta gene segments.

PMID- 8288316
TI  - Stimulation of splenic T-lymphocyte function by endogenous serotonin and by low
      dose exogenous serotonin.
AB  - The modulatory effects of endogenous serotonin on splenic T-cell activity were
      investigated using two distinct approaches. The first approach showed that
      pretreatment of mice with p-cholorphenylalanine (PCPA) to deplete intracellular
      stores of serotonin reduced the capacity of their splenic T cells to proliferate
      and to express interleukin-2 receptor (IL-2R) in response to concanavalin A (Con
      A). These responses could be restored by the addition of serotonin to the spleen
      cell cultures. In contrast, PCPA treatment did not effect stimulation of spleen
      cells to produce IL-2. The second approach showed that T-cell proliferation to
      Con A as well as to IL-2 was diminished by the presence of antagonists to the
      serotonin-2 receptor (5-HT2R). The effects of low doses (100 ng/ml) of
      exogenously added serotonin on functions of normal spleen cells were also
      examined. At this low dose, serotonin stimulated splenic T-cell proliferation in
      response to IL-2, and enhanced both proliferation and IL-2 production in response
      to a suboptimal concentration of Con A. These results show autologous serotonin
      to be required for T-cell activation and that the activation of suboptimally
      stimulated T cells can be augmented with low doses of exogenously added
      serotonin. These data also suggest that the positive regulation of T-cell
      function by serotonin is mediated through 5-HT2R.

PMID- 8288317
TI  - Lymphocyte migration through cultured endothelial cell monolayers derived from
      the blood-retinal barrier.
AB  - Lymphocyte migration across endothelial monolayers, derived from the rat blood
      retinal barrier, was recorded in vitro using time-lapse video microscopy.
      Syngeneic lymphocytes were plated out onto endothelial cell monolayers for 4 hr
      and their surface motility and transmonolayer migration recorded and quantified.
      Under resting conditions lymphocytes, obtained from peripheral lymph nodes (PLN),
      were small, rounded and static with less than 5% migrating across the monolayer.
      Activation of the lymphocytes with concanavalin A (Con A) increased their size
      and surface motility on both interferon-gamma (IFN-gamma)-treated and resting
      endothelia, but did not alter the number migrating across the monolayer. Similar
      results were also found for phytohaemagglutinin (PHA)-activated lymphocytes.
      Interleukin-2 (IL-2)-dependent CD4+ T-cell lines specifically recognizing either
      retinal soluble antigen (S-Ag) or bovine serum albumin (BSA) exhibited
      significantly greater surface motility over the endothelial monolayers than the
      mitogen-activated PLN lymphocytes. By 4 hr, in excess of 50% of the T-cell line
      lymphocytes had migrated across the endothelial monolayer. Treatment of the
      endothelial cells with IFN-gamma caused a small, but not significant, increase in
      the level of T-cell line lymphocyte migration. These results suggest that the
      migration of lymphocytes across central nervous system-derived endothelia is
      primarily dependent upon the state and mode of lymphocyte activation.

PMID- 8288318
TI  - Does interleukin-2 restore lymphocyte responses suppressed by Trypanosoma cruzi?
AB  - There has been disagreement about the ability of exogenous interleukin-2 (IL-2)
      to restore responsiveness to lymphocytes from either Trypanosoma cruzi-infected
      animals or normal individuals co-cultured with this parasite. The discrepancy has
      been attributed to the use of different strains of mice or T. cruzi isolates, or
      to the use of lymphoid cells from different organs. As T. cruzi inhibits the
      expression of IL-2 receptors by activated lymphocytes in vitro, we were able to
      test whether restoration of responsiveness by exogenous IL-2 might depend on the
      level of suppression present in the system. Human or mouse lymphocytes stimulated
      with phytohaemagglutinin (PHA) exhibited gradual decreases in IL-2 receptor
      expression, [3H]thymidine incorporation and IL-2 secretion as the concentration
      of T. cruzi in the culture increased. Exogenous IL-2 afforded a degree of
      restoration of both IL-2 receptor expression and [3H]thymidine uptake which was
      substantial at the lower, but very small--if any--at the higher, parasite
      concentrations tested. Trypanosoma cruzi could not have competed with the
      lymphocytes for IL-2 because it did not bind significant amounts of this
      cytokine. These results suggested that the controversy about the corrective
      effects of IL-2 may be more apparent than real, reflecting variations in the
      extent of immunosuppression present in different model systems of T. cruzi
      associated immunosuppression.

PMID- 8288319
TI  - Cytokine production in the murine response to brucella infection or immunization
      with antigenic extracts.
AB  - In order to induce acquired cellular resistance (ACR) to facultative
      intracellular bacterial pathogens, infection with live organisms is required. It
      is possible that different cytokine responses to live bacteria or their extracted
      antigens could account for their different abilities to induce ACR. Therefore,
      mice were infected with live attenuated Brucella abortus vaccine strain 19, and
      their ability to produce cytokines, both in vivo and in vitro, was investigated
      over 12 weeks of infection. This was compared with the response to injection of
      soluble brucella proteins (SBP). During infection, serum levels of interleukin-6
      (IL-6) were markedly increased over a period of 4 weeks during the peak of
      infection. SBP plus adjuvant induced a transient increase in serum IL-6. IL-1 and
      tumour necrosis factor-alpha (TNF-alpha) remained undetectable in both instances.
      Spleen cells taken at intervals after infection and cultured with brucella
      antigens produced high titres of IL-6, IL-1 and TNF-alpha. Immunization with SBP
      was less efficient than live infection at inducing these cytokines. Of the
      characteristically T-cell-derived lymphokines, interferon-gamma (IFN-gamma)
      production rose 2 weeks after infection, peaking at 6 weeks, while IL-2 was not
      detected until 6 weeks post-infection. Granulocyte-macrophage colony-stimulating
      factor (GM-CSF) was produced in substantial amounts, but IL-3 production was
      minimal. In contrast, spleen cells from mice immunized with SBP produced IL-2 but
      failed to produce IFN-gamma. The implications of these results for the induction
      of ACR are discussed.

PMID- 8288320
TI  - Long-term administration of 13-cis retinoic acid in common variable
      immunodeficiency: circulating interleukin-6 levels, B-cell surface molecule
      display, and in vitro and in vivo B-cell antibody production.
AB  - We have previously shown that retinoids can induce differentiation of B cells in
      vitro as well as in vivo in patients with common variable immunodeficiency (CVI).
      While changes were observed over 1 week when retinoic acid (RA) was added to CVI
      hybridoma cells in vitro, maturation of the patients' B-cell compartment in vivo
      occurred only after 4 months of drug administration. We have now performed a 64
      week open trial of oral 13-cis RA in five patients to see if prolonged treatment
      would result in continued improvement in their humoral immune compartment. In
      this trial, drug was given for 32 weeks followed by a 32-week wash-out period.
      During the treatment, the patients showed changes in a variety of parameters
      indicating an alteration towards normal of their humoral immune systems. This
      change included a fall in the elevated circulating interleukin-6 (IL-6) levels, a
      more normal display of B-cell surface markers (L-selectin and CD20), a decrease
      in B-cell size, and improved in vitro and in vivo B-cell function. In order to
      determine if VH gene use was affected by the retinoid treatment, VH gene
      expression in the CVI patients was characterized. Results showed an unusual
      predominance of non-mutated VH gene sequences, representative of cells that are
      recent bone marrow emigrants. While no common pattern of change occurred in VH
      gene segment use in the patients while on retinoid therapy, large-scale (> 10
      fold) changes in the expression of these genes were observed in each individual
      over time. Taken together, these results provide multiple lines of evidence that
      13-cis RA promotes maturation of B cells in patients with CVI. However, the
      effect appears to be partial, such that stimuli in addition to 13-cis RA will be
      necessary to provide for further B-cell differentiation in order to achieve
      normalization of humoral immunity.

PMID- 8288321
TI  - Characterization of a thyroiditis-inducing thyroglobulin-specific T-cell clone
      restricted by the H-2 molecule of a low responder mouse strain.
AB  - We established a thyroglobulin (Tg)-specific, thyroiditis-inducing T-cell clone,
      B12G, from B6C3F1 mice by the immunization of mouse Tg with lipopolysaccharide
      (LPS) from Klebsiella strain LEN (O3:K1). B12G was Thy-1.2+, CD3+, CD4+, CD18+,
      and CD8-, and could transfer thyroiditis to recipient mice after in vitro
      stimulation with mouse or bovine Tg. Histological examination showed severe
      thyroiditis with predominant infiltrations of polymorphonuclear cells; few
      mononuclear cells were observed. B12G proliferated in response to bovine, mouse,
      porcine, and rat Tg in the presence of irradiated spleen cells, but did not
      respond to chicken or human Tg. H-2b, a low-responder haplotype of experimental
      autoimmune thyroiditis, governed the response of the clone to Tg. B12G produced
      interleukin-4 (IL-4) and IL-6, but not IL-2 or interferon-gamma (IFN-gamma), on
      stimulation with mouse Tg. These findings were different from characteristics of
      previously reported Tg-specific T-cell clones from high-responder mice in terms
      of epitope specificity and cytokine production pattern, raising the possibility
      that the specificities and functions of T cells involved in the development of
      autoimmune thyroiditis in low-responder mice differ from those in high
      responders.

PMID- 8288322
TI  - Lymphocyte vaccination prevents spontaneous diabetes in the non-obese diabetic
      mouse.
AB  - The aim of this study was to investigate whether lymphocyte vaccination can
      prevent diabetes occurring in the non-obese diabetic (NOD) mouse, an animal model
      of human insulin-dependent diabetes mellitus (IDDM). The lymphocyte vaccine was
      composed of lymphocytes isolated from the spleens of diabetic NOD mice, activated
      in vitro using concanavalin A (Con A) and rendered immunogenic using
      glutaraldehyde treatment. These cells were used to vaccinate mice at 6 weeks with
      boosters at weeks 10, 14 and 18. The animals were then monitored for signs of
      diabetes until week 30. Twenty-eight NOD mice (11 male, 17 female) were T
      lymphocyte vaccinated while 35 littermates (14 male, 21 female) were sham
      vaccinated with the vaccine carrier, as control mice. The percentage of mice
      remaining non-diabetic was 50% in the T-lymphocyte-vaccinated group compared with
      20% in control mice (P < 0.05). When the results were divided according to sex of
      the mouse the percentage of female NOD mice remaining non-diabetic was 47.1% in
      the T-lymphocyte-vaccinated group compared to only 9.4% in the controls (P <
      0.01), while in the males there was no significant difference between the groups.
      These results suggest that T-lymphocyte vaccination can prevent diabetes in NOD
      mice and that it has its greatest effect in females. The therapy is apparently
      safe and its efficacy indicates that it may be of value in prediabetes in man.

PMID- 8288323
TI  - Intercellular regulation of major histocompatibility complex class I expression
      in neural cells.
AB  - We have studied the effect of rat central nervous system (CNS) neurons on the
      inducibility of major histocompatibility complex (MHC) class I molecules on
      syngeneic astrocytes. In a co-culture system composed of embryonic rat cortical
      neurons and neonatal astrocytes, intact neurons decreased constitutive expression
      of MHC class I determinants and inhibited the induction of class I products on
      astrocytes. Viability of the neurons and direct contact with astrocytes was
      critical for this effect. Soluble factors released by neurons were inefficient.
      Our data indicate that the lack of MHC class I expression on astrocytes in situ
      might be the result of an active suppression mechanism rather than merely due to
      the absence of activating factors in the CNS.

PMID- 8288324
TI  - Second thoughts on growth monitoring.

PMID- 8288325
TI  - Acquired immunodeficiency syndrome (AIDS) in multitransfused children with
      thalassemia.
AB  - Two hundred and three multi-transfused children with thalassemia attending the
      Thalassemia Clinic of the Charak Palika Hospital, New Delhi were screened for
      human immunodeficiency virus (HIV) antibodies by ELISA and all positive cases
      were confirmed by Western Blot. Of the 203 children screened, 18 (8.9%) were HIV
      positive, and in these children a detailed immunological work up was done and
      compared to 18 age-matched HIV negative thalassemics as controls. The tests
      included absolute lymphocyte counts (ALC), absolute and percentages of CD4+ and
      CD8+ cells and their ratios (CD4/CD8), immunoglobulin levels (IgG, IgM and IgA)
      and delayed cutaneous hypersensitivity (DCH) test by Multitest CMI in all the
      cases and the controls. Of the 18 HIV positive children, 6 were diagnosed to have
      clinical AIDS as per the WHO criteria. After immunological testing, the children
      were further classified according to the CDC criteria. By these criteria, 11
      children were classified as P1 A (asymptomatic infection, normal immune
      function), 1 child as P1 B (asymptomatic infection, abnormal immune function), 2
      children as P2 A (symptomatic infection with non-specific findings), 1 child as
      P2 C (lymphocytic interstitial pneumonitis), 1 child as P2 D1 (Pneumocystis
      carinii pneumonia) and 2 children as P2 D2 (symptomatic infection with
      infections). In this paper, the clinical features of the children with AIDS is
      described, and the immunologic functions of these children are compared with the
      HIV positive asymptomatic children and with controls. These are the first cases
      of AIDS in the pediatric age group from India.

PMID- 8288326
TI  - Immunoglobulin deficiency.
AB  - Twenty three patients with primary immunoglobulin(Ig) deficiency were seen during
      the last ten years. Nine had hypogamma globulinemia (hypo-Ig) and the rest,
      selective Ig deficiency. Most were in pediatric age group. There was
      preponderance of males with only one female. Clinical symptoms pertaining to
      gastrointestinal and sinupulmonary infections were most common. Complete absence
      of B cells was not observed in any patient with hypogammaglobulinemia. They could
      be typed as physiological in one patient, X-linked immunodeficiency in 2 patients
      and common variable immunodeficiency in the remaining six. Three patients with
      selective IgA deficiency were above 20 years of age. Two had only secretory IgA
      deficiency, confirmed by jejunal fluid examination and the rest had both
      secretory and serum IgA deficiency. Low IgM was seen in one patient. We see a
      spectrum of immunoglobulin deficiencies varying from subtle defects like absence
      of secretory IgA only, to severe depletion of all immunoglobulins. Therapy is
      still not ideal due to economic reasons.

PMID- 8288327
TI  - Serum enzyme abnormalities in protein energy malnutrition.
AB  - Six serum enzymes, alkaline phosphatase, cholinesterase, lactate dehydrogenase,
      aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl
      transpeptidase were studied in 30 cases of protein energy malnutrition (PEM). The
      mean serum values of alkaline phosphatase, cholinesterase and lactate
      dehydrogenase in cases of PEM were significantly lower than the controls,
      lowering being maximum in PEM Grade IV. The mean serum values of aspartate
      aminotransferase and alanine aminotransferase in patients with PEM were
      significantly higher than the controls. The mean serum values of gamma-glutamyl
      transpeptidase showed similar significant rise in all but PEM Grade IV. The
      degree of increase in the serum values of these three enzymes were maximum in
      cases with PEM Grade I. These findings suggest that abnormalities in blood levels
      of these enzymes occur in any form of PEM and these are related to the severity
      of the disease.

PMID- 8288328
TI  - Behavior problems among preschool children.
AB  - Of 200 preschool children (aged 3-6 years) screened in the Pediatric Outpatient
      Department, over a period of six months, 44 (22%) had behavior problems. The
      prevalence of behavior problems was higher among boys. Second-born boys and the
      eldest girls had a higher prevalence of temper tantrums, destructive nature,
      difficulty in management and hyperactivity. Fearful reactions and attention
      seeking behavior was encountered only in girls. Behavior problems were more
      common in children from nuclear families and a lower socio-economic status.

PMID- 8288329
TI  - Childhood tuberculosis in a referral centre: clinical profile and risk factors.
AB  - One hundred and ninety six children (age group 6 months to 12 years) attending
      the Pediatric Tuberculosis Clinic at AIIMS, New Delhi, over a period from January
      1988 to December 1989 were analysed. Nearly 61% of children were malnourished
      (Grades III and IV). A positive family history was noted in nearly one third
      (33.7%) of cases while 41.3% of children had received BCG. A positive Mantoux
      test was noted in 77% of cases. The most prominent lesion on radiology was
      parenchymal (51.4%). In nearly two third of cases, both Mantoux test and X-ray
      chest was positive. A family history of tuberculosis and BCG vaccination was
      significantly associated with positive Mantoux test (p < 0.01). Fever and cough
      in older children (> 6 years) while weight loss in younger children (< 3 years)
      were the predominant symptoms. Most of the cases (82.1%) had pulmonary primary
      complex, the proportion being higher in older age group. The severe form of
      tuberculosis, i.e., progressive primary disease, military tuberculosis, etc.,
      were significantly more in younger children. The various risk factors
      significantly associated with severe form of tuberculosis were very young
      children (< 3 years), no BCG vaccination, a negative family history and a
      negative Mantoux test.

PMID- 8288330
TI  - Bone mineral content in normal and malnourished children.
AB  - Bone mineral content (BMC) was determined at the distal radius in 70 children
      aged 2-14 years; Group I comprising 34 normal healthy children and Group II 36
      malnourished children by the method of single photon absorptiometry. The mean
      value of BMC in Group I was 0.3 +/- 0.04 g/cm in 2-5 year, 0.52 +/- 0.08 g/cm in
      6-10 year and 0.77 +/- 0.88 g/cm in 11-14 year age groups. No significant
      difference in the BMC was seen between boys and girls. An increase of BMC
      corresponded to growth spurts in 2-5 year and 11-14 year age groups. There was a
      significant reduction of BMC in Group II and in grade III malnutrition in 2-5
      year and 11-14 year age groups as compared to Group I children. The study
      provides normal BMC data for Indian children and suggests that this can help to
      detect undemineralization of bones in malnourished children during the growth
      periods.

PMID- 8288331
TI  - Bacterial meningitis: diagnosis by latex agglutination test and clinical
      features.
AB  - To know the usefulness of Latex Agglutination Test (LAT) for the diagnosis of
      bacterial meningitis (BM), it was performed in all the 114 consecutive samples of
      CSF with polymorphs from 114 prospectively recruited children aged 2 months to 11
      years. Definite diagnosis of BM based on culture and/or LAT was evident in 55.
      Among the 46 LAT positive, culture was positive in 3 only. Major organisms
      identified by LAT were H. influenzae B (HiB) in 28 and S. pneumoniae (SP) in 15.
      Ninety per cent of HiB and 67% of SP bacterial meningitis were under one year of
      age. Fever > 7 days prior to admission was not uncommon (38%) and 26% had
      received prior antibiotics. Meningeal signs were present in 64%. CSF cells were <
      500/mm3 in 24% and sugar was > 50% of blood level in 23%. There was no
      significant difference in the immediate outcome between HiB and SP meningitis.
      The case fatality was 22% and was significantly high in cases who had altered
      level of consciousness on admission (p = 0.02). It is concluded that LAT is very
      useful for rapid diagnosis of BM.

PMID- 8288332
TI  - Pregnancies in adolescents: fetal, neonatal and maternal outcome.
AB  - We studied the perinatal morbidity and mortality among adolescent pregnancies in
      the semi-urban population of Gorakhpur. The number of eligible couples (females
      15-44 yrs) were 24,000. Out of 430 adolescent married girls, 242 (56.3%) became
      pregnant during the study period. Nineteen (7.8%) of adolescent pregnancies were
      in the maternal age group less than 15 years and 110 (45.5%) and 113 (46.7%)
      pregnancies were in the age group 15-17 yrs and 17-19 yrs, respectively. The
      incidence of low birth weight babies was 67.3% of all live births. Infections
      during neonatal period, congenital anomalies and birth injuries were seen in
      21.6, 8.6 and 13.1% newborns, respectively. Neonatal mortality rate was
      136.2/1000 live births. Three adolescent mothers died during pregnancy or
      puerperium due to causes related to pregnancy. The incidence of LBW, neonatal and
      maternal morbidity and mortality associated with adolescent pregnancies were
      significantly higher.

PMID- 8288333
TI  - Chloramphenicol resistant enteric fever.

PMID- 8288334
TI  - Perinatally acquired AIDS.

PMID- 8288335
TI  - HIV seroconversion in a young child following a single blood transfusion.

PMID- 8288336
TI  - Salmonella senftenberg septicemia: a nursery outbreak.

PMID- 8288337
TI  - Citrobacter septicemia in neonates.

PMID- 8288338
TI  - Vitamin A and post measles complications.

PMID- 8288339
TI  - Citrullinemia and transposition of the great arteries.

PMID- 8288340
TI  - Cerebro vascular accident in mitral valve prolapse.

PMID- 8288341
TI  - Embolic stroke in myocarditis.

PMID- 8288342
TI  - Demonstration of brain lesions in tuberous sclerosis by magnetic resonance
      imaging.

PMID- 8288343
TI  - Lesch-Nyhan syndrome.

PMID- 8288344
TI  - Posterior sagittal rectopexy for rectal prolapse.

PMID- 8288345
TI  - An unusual presentation of infantile gangrenous acalculous cholecystitis.

PMID- 8288346
TI  - Dieulafoy's lesion in a child.

PMID- 8288347
TI  - Antenatal diagnosis of conjoined twins with multiple malformations.

PMID- 8288348
TI  - Brain stem abscess.

PMID- 8288349
TI  - Unusual presentation of tuberculous peritonitis.

PMID- 8288350
TI  - Generalized BCG tuberculosis.

PMID- 8288351
TI  - Lymphangioma of scrotum.

PMID- 8288352
TI  - Acyclovir.

PMID- 8288353
TI  - Congenital syphilis: a reappraisal.

PMID- 8288354
TI  - Vitamin A and child survival.

PMID- 8288355
TI  - Treatment of intra-articular fractures with shape memory compression staples.
AB  - The management of intra-articular fractures remains difficult. Shape memory
      compression staples fulfil nearly all the special treatment requirements of intra
      articular fractures. Early bone union and 93.5 per cent satisfactory function
      were achieved in a series of 121 cases. Stable fixation, 'early' movement and
      continuous compressive force produced by the staple are the main factors
      contributing to good results.

PMID- 8288356
TI  - Holding power of the 4.5 mm AO/ASIF cortex screw in cortical bone in relation to
      bone mineral.
AB  - To obtain basic data about the holding power of a 4.5 mm AO/ASIF cortex screw in
      cortical bone in relation to bone mineral as expressed by densitometric methods,
      uniaxial pull-out tests were performed on 14 human cadaver femurs. The mechanical
      parameters were correlated with bone mineral which was assessed by quantitative
      computed tomography (QCT) and dual energy X-ray absorptiometry (DXA). High
      correlations were found between the QCT mass, the DXA density and content values
      and the holding power of the screw. The QCT density values, expressing the
      physical density of the bone, did not correlate similarly well.

PMID- 8288357
TI  - Evaluation of the conventional stretcher as a support surface.
AB  - The conventional wood and canvas stretcher was evaluated with regard to comfort
      and risk of pressure and ischaemic damage. Sixty subjects were evaluated and
      results were found to be similar to other support surfaces. A mean sacral
      interface pressure of 40.7 mmHg was noted. Subjects found the stretchers cold and
      uncomfortable, particularly over the heels and lower back.

PMID- 8288358
TI  - The Kapandji procedure for post-traumatic problems.
AB  - The Kapandji procedure was performed on 14 patients who presented with chronic
      pain at the distal radioulnar joint, limited forearm rotation or poor grip after
      an injury involving the distal radioulnar joint. Ten patients were able to resume
      their original occupation and leisure activities. Some complained of mild aching
      after heavy use. Postoperatively, grip strength on the affected side was, on
      average, 84 per cent that of the opposite side. Forearm rotation in the affected
      arm averaged 129 degrees before operation and 170 degrees afterwards, compared
      with 171 degrees on the normal side, while wrist flexion-extension averaged 129
      degrees preoperatively, 126 degrees postoperatively and 148 degrees on the normal
      side. Four patients had less satisfactory results because of pain and a feeling
      of insecurity due to an unstable proximal ulna. However, two of these had severe
      residual problems in relation to the initial forearm component of the injury, the
      symptoms from which were difficult to separate from the distal radioulnar injury.
      Although the Kapandji procedure can yield excellent results, it is difficult to
      predict which patients will suffer from an unstable ulna.

PMID- 8288359
TI  - Shotgun wounds of the limbs.
AB  - Shotgun blasts may cause devastating injuries in civilian trauma practice. We
      have reviewed 23 consecutive patients with 28 deliberate shotgun wounds to limbs
      treated over a 4-year period. Wounds were categorized using the Red Cross wound
      classification. Twenty wounds were high-energy transfer grade 2 and 3 injuries:
      eight involved only the soft tissues (five category 2ST, three category 3ST), 10
      wounds involved fractures (two category 2F, seven category 3F, one category 3VF),
      and three wounds involved major vessel injury (two category 3V, one category
      3VF). Category 2ST and 3ST wounds were managed successfully with thorough wound
      excision of devitalized tissue, fasciotomy, and early wound closure. The more
      complex category 3F, 3V and 3VF wounds required a multidisciplinary approach to
      their management. Three lower limbs (category 3F, 3V, and 3VF wounds) with
      associated major nerve injury were amputated at the first operation; there were
      no cases of secondary amputation. Of the salvaged limbs, those with category 3F
      injury at or below the level of the elbow or knee had poor functional results.

PMID- 8288360
TI  - Hyponatraemia after acute spinal injury.
AB  - Of 134 patients admitted to the Midlands Centre for Spinal Injuries within 2 days
      of the spinal injury during 1991-1992, 25 developed hyponatraemia in the acute
      phase. Hyponatraemia was most common among patients with complete tetraplegia (45
      per cent) and these patients tended to be younger as well as have more severe and
      prolonged hyponatraemia. Overhydration is a common cause of hyponatraemia in this
      group of patients and should be avoided.

PMID- 8288361
TI  - Hyperextension-dislocation injuries of the cervical spine.
AB  - Between 1965 and 1991, 132 patients with vertebral dislocation following
      hyperextension injury of the cervical spine were treated at the Spinal Injury
      Department of the Metropolitan Rehabilitation Centre in Konstancin, Poland. The
      series accounted for over 25 per cent of patients with hyperextension injuries
      and for about 7 per cent of all cervical-spine-injured patients treated during
      these years. These changes are most commonly found in two situations: (1)
      Injuries of the upper cervical spine. (2) Injuries sustained by individuals with
      advanced pathological changes in the spine. Such conditions are found in advanced
      spondylosis and ankylosing spondylitis. Such changes were noted in nearly 65 per
      cent of the patients in the series analysed. The improved results seen in
      surgically treated patients encourage the wider application of surgery in such
      groups of patients.

PMID- 8288362
TI  - Blunt traumatic flank hernia.

PMID- 8288363
TI  - Association of seating arrangements and multiple pelvic fractures in a road
      traffic accident.

PMID- 8288364
TI  - Bilateral inferior shoulder dislocation: both subglenoid and subcoracoid types
      seen in the same patient.

PMID- 8288365
TI  - Recurrent ipsilateral fracture of the penis.

PMID- 8288366
TI  - Camel bite injury: an unusual report of left shoulder mutilation with major
      vascular and bony injuries.

PMID- 8288367
TI  - Trivial chest injury: a case for vigilance.

PMID- 8288368
TI  - Delayed papillary muscle rupture following non-penetrating chest injury.

PMID- 8288369
TI  - Simultaneous bilateral hip fractures presenting as an acute abdomen.

PMID- 8288370
TI  - Spontaneous subcapital femoral neck fracture complicating a healed
      pertrochanteric fracture: aetiology and ease of diagnosis is not as previously
      thought.

PMID- 8288371
TI  - A second proximal femoral fracture caused by failure of a sliding hip screw.

PMID- 8288372
TI  - Flexor pollicis longus rupture.

PMID- 8288373
TI  - Rupture of the ulnar collateral ligament of the metacarpophalangeal joint of the
      thumb.

PMID- 8288374
TI  - Pin placement in pelvic external fixation.
AB  - Early external fixation of major pelvic fractures reduces haemorrhage and
      mortality. The best site and method for pin placement remains unresolved. The
      superior iliac crest is biomechanically disadvantageous and hinders access to the
      abdomen. Low pin placement between the anterior iliac spines has been proposed as
      a better solution. A case-controlled study was performed on cadavers using a jig
      designed to place external fixator pins accurately in the pelvis; the study
      tested the safety of pin placement and the mechanical strength of the two
      placement sites. The results showed that pins could be placed safely using this
      method and that low placement in cadaveric bone is as strong as that of the
      conventional placement.

PMID- 8288375
TI  - Use of biodegradable (PGA) fabric for repair of solid organ injury: a combined
      institution experience.
AB  - A fabric constructed of biodegradable mesh was used in the operative repair of
      injured intra-abdominal organs in 60 patients at two Level I Trauma Centres.
      Splenorrhaphy was performed in 44 patients, hepatorrhaphy in eight, renorrhaphy
      in five and one combined repair of spleen and liver and one kidney and liver. The
      age range for the patients was 5 to 61 years. Multiple-organ injury occurred in
      21 patients. Mean emergency room systolic BP for the patient series was 120 +/-
      24 mmHg (SD), Glasgow Coma Scale 14.3 +/- 1.9, haematocrit 37.2 +/- 6.4 per cent,
      Injury Severity Score (ISS) 28.1 +/- 16.3, Abdominal Trauma Index (ATI) 15.5 +/-
      7.5. Postoperative complications occurred in 36.7 per cent of patients. Time for
      the operation averaged 165.1 + 72.1 min and preoperative and operative
      transfusion volume averaged 2248 ml. There were three deaths (5.4 per cent). The
      mesh organ repair technique is an alternative to conventional surgical procedures
      used to control bleeding from injured organ surfaces and to close organ
      parenchymal defects.

PMID- 8288376
TI  - Tibial shaft fractures with an intact fibula.
AB  - The effect of several factors on the healing rates of tibial shaft fractures with
      an intact fibula were examined. Those found to adversely affect healing rates
      included: 1. Open fractures; 2. Oblique or comminuted fractures; 3. High-velocity
      injuries; 4. Angulation in the sagittal plane; 5. Displacement. No other factors
      examined were associated with delayed union. The predictive values for delayed
      union are estimated for each of these factors in isolation and in combination.

PMID- 8288377
TI  - Colostomy in trauma surgery: friend or foe?
AB  - Twenty-five patients underwent a colostomy that came to closure. There were eight
      blunt, 15 penetrating and two impaling injuries. Colostomy-related complications
      occurred in four patients; two wound infections, one stoma prolapse, one loop
      obstruction. Closure was performed during a second hospital stay after a standard
      mechanical bowel preparation and enteral and parenteral broad-spectrum
      antibiotics perioperatively. The procedure performed by board certified/eligible
      surgeons, lasted an average of 2.5-3h. Incisional hernias occurred as the only
      complication in two patients. For certain injuries of the colon, rectum and
      perineum, diverting colostomy is still the procedure of choice. It can be
      performed without significant additional morbidity. Subsequent closure in
      experienced hands does not carry a significant complication rate.

PMID- 8288378
TI  - Gulf war wounds: application of the Red Cross wound classification.
AB  - The Red Cross wound classification was applied to 63 casualties requiring surgery
      in the recent Gulf war. The majority of wounds affect only soft tissue, caused
      predominantly by antipersonnel fragments. Bullet wounds were fewer but tended to
      be more severe, often involving a fracture or vascular damage. We recommend minor
      modification to the classification to include scoring of significant neurological
      injury. Further, we feel that by recording the distribution of all wounds as well
      as scoring the casualty's two worst injuries, the incidence and pattern of
      multiple wounds are ascertained, which is useful in military surgical research.
      We believe that the Red Cross wound classification is valuable in assessing a
      wound as part of a secondary survey, but that this wound score has little part to
      play in triage. It may help to decide management of individual wounds in clinical
      practice and is useful for recording the nature of wounds for future analysis.

PMID- 8288379
TI  - A deep lateral femoral notch as a sign of acutely torn anterior cruciate
      ligament.
AB  - Anterior cruciate ligament (ACL) tears are frequently associated with
      abnormalities of the lateral femoral condyle as shown by magnetic resonance
      imaging. The mechanism of injury has been described as due to bone compression
      during knee trauma. This may lead to compression of the lateral condylopatellar
      notch (sulcus). It has been suggested that detection of a deep notch on the plain
      lateral radiograph is a useful indirect sign of ACL tear. Depth of this notch was
      measured in 34 consecutive prospective patients assessed as having acute ACL tear
      clinically and proven at arthroscopy. In no patient was the notch deep,
      suggesting that this is not a useful sign in acute tears of the anterior cruciate
      ligament.

PMID- 8288380
TI  - Brachial plexus injury: when to amputate?
AB  - Amputation of the upper limb was performed in 20 out of 750 patients with
      traction lesions of the brachial plexus between August 1969 and June 1991. Urgent
      amputation was necessary in three patients with irreparable vascular injury and
      in two more because of overwhelming sepsis. Thirteen patients chose amputation of
      their flail and useless arm. Two patients have been lost to follow-up. Urgent
      amputation is indicated when perfusion of the limb cannot be restored, for
      sepsis, and for a limb which is so severely injured that there can be no prospect
      for a return of any function. Elective amputation is performed at the patient's
      request and may be considered as an element of rehabilitation. The pain of
      preganglionic injury of the brachial plexus is not relieved by amputation.

PMID- 8288381
TI  - Amputees in a hospital of the International Committee of the Red Cross.
AB  - The object of this study is to describe the treatment of patients with an
      amputation in terms of causes and distribution of injuries, mortality and drain
      on surgical resources. A group of patients with war injuries, who did not undergo
      an amputation (1796) and a group of war-injured patients with an amputation (245)
      were analysed retrospectively. All these patients were treated in the hospital
      for Afghan war wounded of the International Committee of the Red Cross. The most
      common amputation was below-knee amputation (BKA). In more than 90 per cent of
      the patients a BKA was the result of a mine explosion. About 80 per cent of
      amputations of the lower limb were caused by antipersonnel mines. The upper limb
      amputations were mainly caused by mines or by fragments. War-injured patients
      with an amputation face more serious problems than non-amputated patients. Their
      mortality is higher, they stay longer in the hospital, the risk of infection is
      higher, they need more blood and they undergo more surgical interventions. The
      high percentage of non-combatants stresses the need to give civilians better
      protection against the indiscriminate use of mines.

PMID- 8288382
TI  - Hemiarthroplasty of the hip--the anterior or posterior approach? A comparison of
      surgical approaches.
AB  - A series of 531 patients presenting with a displaced subcapital femoral fracture
      treated by hemiarthroplasty, were studied prospectively to determine the optimal
      approach for surgery. A total of 302 prostheses were inserted by an anterolateral
      approach and 229 by a posterolateral approach. Complications in these two broadly
      comparable groups are discussed. Dislocation and thrombosis were more common
      after a posterior approach. Operative time, blood loss, and infection, were
      greater after an anterior approach. There was no significant difference in the
      length of hospital stay or mortality. Our findings suggest that favoured approach
      should be that at which the surgeon feels more competent.

PMID- 8288383
TI  - Wet cement: a poorly recognized cause of full-thickness skin burns.
AB  - Cement is a rare cause of full-thickness burns. We have examined the aetiology,
      frequency and severity of these burns, and assessed public awareness of the
      potential of cement as a caustic agent. Of patients, 95 per cent were unaware of
      the potential of cement to cause burns, and none had seen precautionary warnings
      on cement bags or delivery dockets. Factors important in burn production appear
      to be alkalinity, duration of contact and the abrasive nature of the cement
      particles. It is concluded that doctors, especially casualty officers, should
      know of the potential of progressive full-thickness burns from wet cement.
      General public awareness should be increased. The cement manufacturers were asked
      to comment on the content of this paper.

PMID- 8288384
TI  - Missed urological injuries in children with polytrauma.
AB  - Fifteen children (11 boys and 4 girls) with severe injuries of the urinary tract
      were admitted to the Riyadh Central Hospital between 1990 and 1992. Their ages
      ranged from 2.5 to 12 years (mean 7.3 years), and their injuries were parts of
      multiple-organ trauma. Following resuscitation, every child was evaluated and
      staged by either intravenous urography, CT scan or ultrasonography or a
      combination of these. Commonly associated injuries were to the skeleton, spleen
      and liver. Two patients with ureteropelvic junction injuries and two girls with
      traumatic urethropaginal fistulas were not diagnosed. The delay in diagnosis
      contributed to an increase in morbidity. Despite modern radiological imaging,
      some severe injuries of the urinary tract can still be missed. Heightened
      awareness and thorough clinical examination are mandatory for early diagnosis of
      such injuries in children with multiple injuries.

PMID- 8288385
TI  - Double right atrial tear in blunt cardiac trauma.

PMID- 8288386
TI  - Occipitocervical fixation of a complex upper cervical fracture.

PMID- 8288387
TI  - Small bowel entrapment in an iliac wing fracture.

PMID- 8288388
TI  - Use of MAST to control massive bleeding from pelvic injuries.

PMID- 8288389
TI  - Non-union of an os calcis fracture.

PMID- 8288390
TI  - Ultrasonography for a radiolucent foreign body in palm.

PMID- 8288391
TI  - Aeromonas hydrophila wound infection associated with water immersion: an unusual
      football injury.

PMID- 8288392
TI  - A simple external fixator for metacarpal and phalangeal fractures.

PMID- 8288393
TI  - Post-traumatic Beau lines.

PMID- 8288394
TI  - Shotgun trauma of the abdomen treated by wide excision, laparotomy and free
      latissimus dorsi flap.

PMID- 8288395
TI  - Gastrocnemius tendon rupture: a new clinical entity?

PMID- 8288397
TI  - Take a Xanax and I'll call you in the morning.

PMID- 8288396
TI  - Management of skeletal trauma in the UK.

PMID- 8288398
TI  - Checking it once, checking it twice.

PMID- 8288399
TI  - Ownership matters: health reform and the future of nonprofit health care.

PMID- 8288400
TI  - Implications of a global budget for facility-based health spending.
AB  - This paper compares the five-year forecast growth in hospital, nursing facility,
      and home health expenditures to the growth that would result if three alternative
      global budget targets were met. Implementing a global budget offers the potential
      for substantial savings, but achieving this potential would be difficult. Except
      in the hospital inpatient sector, it would be nearly impossible to meet a target
      based on growth in gross domestic product without finding a way to curtail the
      current trend of volume increases. We believe it also would be necessary to
      reduce the gap between economywide inflation and inflation in the prices of goods
      and services that health facilities buy.

PMID- 8288401
TI  - Strategic choices for cost containment under a reformed U.S. health care system.
AB  - The Clinton administration health reform proposal would impose global spending
      limits to bring the rate of increase in health care spending into line with the
      Consumer Price Index by 1999. This paper examines cost containment strategies
      available to states and health plans under externally imposed revenue limits.
      Drawing on the experience of state and local regulatory agencies, private sector
      managed care plans, and models in other countries, we contrast premium caps and
      provider rate setting as mechanisms to reduce growth in health care spending, and
      briefly consider the system-level regulatory structures necessary to oversee and
      control aggregate health care spending.

PMID- 8288402
TI  - Expenditure limits and cost containment.
AB  - The Clinton administration's proposal for health care reform would tie limits on
      premiums and, indirectly, provider payment rates to a national health care
      budget. An expenditure limit (or global budget) is a mechanism to calibrate the
      parameters of underlying cost containment policies. This article analyzes
      provider rate setting and managed competition and discusses how they can be
      guided by expenditure limits. Particular attention is paid to health systems that
      include elements of both traditional fee-for-service insurance and organized
      systems of care. Success in containing costs also will require additional
      policies that can supplement rate setting and managed competition to achieve
      specific goals to slow spending growth.

PMID- 8288403
TI  - Does employment-related health insurance inhibit job mobility?
AB  - Most private health insurance in the United States is an employment-related,
      nonportable fringe benefit. As a result, severing an employment relationship can
      lead to a loss of such coverage. The risk of losing coverage has been identified
      as a primary reason for not changing jobs and has shaped the debate over health
      care reform. This paper examines the relationship between employment-related
      health insurance and job mobility. We model the likelihood that a worker
      voluntarily changes employment, based upon insurance status and wages at an
      initial job, expected insurance status and wages at alternative employment, other
      fringe benefits, and worker and dependent health status. Analyses of data from
      the 1987 National Medical Expenditure Survey support the "job lock" hypothesis.

PMID- 8288404
TI  - Physician responses to Medicare physician payment reform: preliminary results on
      access to care.
AB  - This paper examines the impact of Medicare physician payment reform on access to
      care by comparing several physician-based access measures in the pre- and post
      reform periods. The results suggest that the broad goals of payment reform may
      have been at least partially achieved: the proportion of physician revenues
      derived from Medicare increased for primary care physicians and decreased for
      nonprimary care MDs; there was little change in the absolute or relative number
      of visits provided to Medicare patients; and an increasing number of physicians
      charged no more than the Medicare payment amount. Some signs of deteriorating
      access were found, however. Fewer physicians were willing to treat all new
      Medicare patients and more physicians accepted no new Medicare patients.
      Furthermore, there was an increase in the proportion of physicians who reduced or
      stopped providing to Medicare patients certain types of services that they
      continued to provide to other patients.

PMID- 8288405
TI  - A comparison of S/HMO disenrollees and continuing members.
AB  - Four Social/Health Maintenance Organization demonstration projects had
      disenrollment rates of about 8.6% annually during the first 36 months. This study
      compares those who disenrolled to those who remained S/HMO members. The analysis
      found that S/HMOs sponsored by HMOs had lower disenrollment than S/HMOs sponsored
      by long-term care organizations. The major reasons for disenrollment were
      dissatisfaction with physician services and premium costs. Having other
      insurance, not living alone, having inadequate information upon enrollment,
      having no physical impairments or health problems, and no use of hospital or
      chronic care were found to be positive predictors of disenrollment. Switching
      from the S/HMO to another HMO rather than to fee-for-service was associated with
      having no health problems, having no other health insurance, living alone, and
      being married.

PMID- 8288406
TI  - Amending the National Practitioner Data Bank reporting requirements: are small
      claims predictive of large claims?
AB  - This study addresses whether a physician incurring small malpractice claims is
      predictive of large claims. This is one consideration behind reevaluating whether
      all claims that result in an indemnity payment should continue to be reported to
      the National Practitioner Data Bank, or whether claims with payments below some
      "floor" should be excluded. Using a claims database from 3,098 physicians for
      1977-1986, both cross-sectional and longitudinal analyses show that an individual
      having a small claim (under $30,000) is indicative of a propensity to incur large
      claims. This finding is robust to the cutpoint between large and small claims.

PMID- 8288407
TI  - Using claims data to monitor hospital utilization.
AB  - Controlling provider use is a continuing problem for health care insurers. This
      paper describes a Blue Cross and Blue Shield of Michigan system that places
      primary responsibility for inpatient admissions on participating hospitals and
      uses a dual monitoring approach. Expensive annual samples that review medical
      records against published criteria constitute the basic test of compliance. An
      inexpensive indicator is developed quarterly using automated universal claims
      review. Statistical methodology, costs, and savings for both monitors are
      described. The claims monitor uses diagnosis related group (DRG) characteristics
      to estimate the percentage of inappropriate utilization from historical values
      for the patient group.

PMID- 8288408
TI  - Effect of metoprolol and diltiazem on the total ischaemic burden in patients with
      chronic stable angina: a randomized controlled trial.
AB  - We conducted a randomised controlled trial to study the effects of metoprolol and
      diltiazem on the total ischaemic burden--sum of symptomatic and silent myocardial
      ischaemia, in 146 patients with stable angina pectoris. One-hundred thirty-four
      completed the study protocol. Sixty-eight patients received metoprolol (100 mg
      twice daily, n = 52, 50 mg twice daily, n = 16) while 66 received diltiazem (90
      mg three times daily, n = 50, 60 mg three times daily, n = 16). The drugs were
      given for 4 weeks. The primary outcome variables were frequency and duration of
      total ischaemic burden, silent and symptomatic myocardial ischaemia. These were
      measured on 48 h of Holter monitoring. The reductions in duration and frequency
      of total ischaemic burden by metoprolol, 76% and 40%, respectively, were
      significantly higher than by diltiazem, 43% and 24%, respectively (P < 0.01 and P
      < 0.02). The frequency and duration of silent myocardial ischaemia, which
      constituted more than 80% of the total ischaemic burden in the two groups showed
      similar results. However, the reduction in frequency of symptomatic myocardial
      ischaemia only was significantly greater by metoprolol (63% than diltiazem (24%)
      as the difference in reduction of duration of symptomatic ischaemia was
      insignificant (85% vs. 75%; P > 0.05). Whether a greater reduction of total
      ischaemic burden by metoprolol as compared to diltiazem has any implications for
      prognosis in patients with chronic stable angina remains to be established.

PMID- 8288409
TI  - Difference in plasminogen activator inhibitor activity between non-Q-wave
      infarction and Q-wave infarction.
AB  - We examined the plasma levels of tissue plasminogen activator antigen and
      plasminogen activator inhibitor activity in 14 patients with non-Q-wave
      infarction and in 27 patients with Q-wave infarction before the start of
      thrombolytic therapy and in 34 control subjects. The mean level of plasma tissue
      plasminogen activator antigen (ng/ml) was higher (P < 0.01) both in the patients
      with non-Q-wave infarction and in those with Q-wave infarction than in the
      control subjects (10.3 +/- 1.9, 9.5 +/- 0.8 vs. 5.8 +/- 0.3), and there was no
      difference in the level between the patients with non-Q-wave infarction and those
      with Q-wave infarction. The mean level of plasma plasminogen activator inhibitor
      activity (IU/ml) was lower (P < 0.01) in the patients with non-Q-wave infarction
      than in those with Q-wave infarction (7.3 +/- 2.0 vs. 17.1 +/- 2.2), and there
      was no difference in the level between the patients with non-Q-wave infarction
      and the control subjects (7.3 +/- 2.0 vs. 4.1 +/- 2.6). The patency rate of
      infarct-related coronary artery before thrombolytic therapy was higher (P < 0.01)
      in the patients with non-Q-wave infarction than in those with Q-wave infarction
      (54% vs. 15%). We conclude that plasminogen activator inhibitor activity was
      lower in non-Q-wave infarction than in Q-wave infarction and this may be related
      to the higher patency rate of infarct-related coronary artery in non-Q-wave
      infarction.

PMID- 8288410
TI  - Human heart-type cytoplasmic fatty acid-binding protein in serum and urine during
      hyperacute myocardial infarction.
AB  - We have previously reported that serum and/or urinary human heart-type
      cytoplasmic fatty acid-binding protein (HH-FABPc) can be used as an early
      indicator of myocardial injury (Clin Biochem 1991; 24: 195-201). To confirm the
      usefulness of HH-FABPc as an early diagnostic indicator of acute myocardial
      infarction (AMI), its serum and urinary levels were measured in samples obtained
      within 6 h after the onset of acute coronary syndrome related symptoms. Samples
      were collected from 97 patients, who were composed of 63 with AMI, 24 with
      unstable angina and 10 with chest pain syndrome. The positivity of serum and
      urinary HH-FABPc and cardiac creatine kinase isozyme MB (CK-MB) was analyzed in
      these samples. Serum HH-FABPc levels in AMI were above normal in 91.4% (64/70) of
      the samples tested within 3 h of the onset of symptoms and in 100% (111/111) of
      those tested at 3-6 h. Elevated urinary HH-FABPc levels in AMI were obtained in
      88.9% (8/9) of samples at 0-3 h and in 75% (6/8) at 3-6 h. CK-MB activity in AMI
      was positive in 20% (8/40) and 66.3% (53/80) of serum samples at 0-3 h and 3-6 h,
      respectively. HH-FABPc was always positive when a serum sample was positive for
      CK-MB. Serum HH-FABPc at 0-6 h in chest pain syndrome and in unstable angina were
      positive in 17.8% (5/28) and 56.7% (34/60), respectively. The elevated HH-FABPc
      in serum and urine was noted much earlier than that of CK-MB during the
      hyperacute phase of AMI. HH-FABPc showed high positive value in unstable angina,
      but it was low in normal coronary patients having chest pain. However, HH-FABPc
      level in unstable angina and chest pain syndrome was lower than that of AMI.
      Thus, HH-FABPc may be a valuable indicator for the diagnosis of hyperacute
      myocardial infarction.

PMID- 8288411
TI  - Left ventricular filling rate at rest and during exercise in patients with
      previous myocardial infarction.
AB  - The purpose of this investigation was to define, with radionuclide technique, the
      variation on left ventricular filling rate in patients with coronary artery
      disease, and to determine the effects of dynamic exercise on this variation. The
      study was carried out on 91 subjects, 46 patients with anterior and 30 with
      inferior previous transmural myocardial infarction; 15 healthy subjects were
      studied as control group. All the patients underwent coronary angiography and
      left ventriculography. From the left ventricular time activity curve we
      considered the diastolic parameters of the peak filling rate (PFR). We considered
      also the relative end-diastolic volume (rEDV) and the relative end-systolic
      volume (rESV). These parameters were determined at rest and at the fifth minute
      of a symptom limited dynamic exercise taken in the supine position, on an
      ergometric bicycle. In normal subjects rest mean PFR values is 3.08 +/- 0.51
      edv/s, during exercise occurs a physiological increase and mean PFR values
      becomes 5.48 +/- 1 edv/s. The patients with previous myocardial infarction show a
      PFR significantly smaller than in normal subjects. Abnormal PFR indices during
      exercise are present in a large number of these patients and the higher anomalies
      of PFR during exercise were found among patients with anterior myocardial
      infarction. In these patients we found an increase of rESV during exercise. In
      conclusion myocardial infarction induces significant alterations of the PFR;
      physical exercise reveals PFR alterations not exhibited at rest and rESV increase
      during exercise could be responsible for the PFR alteration observed.

PMID- 8288412
TI  - Clinical profile of biopsy proven idiopathic myocarditis.
AB  - We studied 20 patients in detail (age: 27 months to 45 years, mean 22 years; 15
      males, 5 females) of idiopathic myocarditis histologically confirmed by
      endomyocardial biopsy. None of these patients had evidence of active or previous
      rheumatic fever. The commonest mode of presentation was congestive heart failure
      (16 patients) followed by arrhythmias (seven patients--five of whom had
      associated congestive heart failure) and chest pain resembling myocardial
      infarction (two patients). Ten patients had a history of preceding upper
      respiratory infection. Only one of these patients had a significant rising serum
      titre for Coxsackie B3 virus. Throat and rectal swabs for virus culture were
      negative in all patients. The electrocardiogram was abnormal in all patients,
      with a prolonged corrected QT-interval being the commonest abnormality (14
      patients). Serial electrocardiographic patterns of evolving myocardial infarction
      occurred in three patients. Echocardiographic left ventricular end diastolic
      dimension (4.15 +/- 1.01 cm/m2) and end systolic dimension (3.37 +/- 1.03 cm/m2)
      were increased in 15 of the 18 patients studied. Pericardial involvement occurred
      in only one patient. Radionuclide ventriculography showed a reduced left
      ventricular ejection fraction (< 50%) in 17 patients, global hypokinesia in 12
      patients and regional wall motion abnormalities in five patients. Left
      ventricular and right ventricular end diastolic pressures were elevated in 15 and
      11 patients, respectively.

PMID- 8288413
TI  - Pulmonary valve origin of pedunculated rhabdomyoma causing moderate right
      ventricular outflow obstruction: surgical-implications.
AB  - A rare case of single, pedunculated, ball-like rhabdomyoma of the pulmonary
      valve, causing moderate right ventricular outflow obstruction in an infant with
      tuberous sclerosis, is presented. The diagnostic and surgical implications are
      discussed.

PMID- 8288414
TI  - An acardiac infant: the extreme form of the twin-twin transfusion syndrome.
AB  - A description of the pathologic and clinical findings in a twin with twin-to-twin
      transfusion syndrome is given. One of them died immediately after birth, with the
      autopsy revealing the histologic absence of the myocardium. The surviving infant
      presented with short term heart failure and with persistent left ventricular
      hypertrophy over 6 months. The circulatory changes in the twin-to-twin
      transfusion syndrome can result in complete myocardial involution in one and an
      unexpectedly long compensatory left ventricular hypertrophy in the other infant.
      Caution is advised in order to avoid misdiagnosing hypertrophic cardiomyopathy.
      In such a case a longer follow-up period is recommended.

PMID- 8288415
TI  - Bacterial pericarditis caused by Salmonella enteritidis phage type 1.

PMID- 8288416
TI  - Father involvement in infant care: two longitudinal studies.
AB  - Data collected from two samples of fathers in separate longitudinal studies were
      compared. One sample consisted of 53 first-time fathers and the other of 69
      multiple-time fathers. A post-test only time-series design was used for both
      studies, and both employed the same procedures and instruments. The studies
      examined role enactment of fathers with different child-caring experiences using
      role-theory concepts. Fathers' normative expectations, personal expectations, and
      personal learning about parenting were tested to determine if they were
      predictive of paternal role performance. The findings seem to indicate that the
      culture of fatherhood has changed more rapidly than the conduct of fatherhood.

PMID- 8288417
TI  - Nursing's syntax revisited: a critique of philosophies said to influence nursing
      theories.
AB  - Lodged within the syntax of a discipline are the value systems and research
      constraints that influence theory development and research strategies. Humanism
      and postmodern philosophy have challenged natural science philosophical
      influences on nursing's syntax. This paper examines the construction of nursing's
      syntax from empiricist, hermeneuticist, feminist, and critical social theory
      views. In this critique, two requirements are placed on the world views: (1) they
      must accommodate theoretical (realist) terms important to nursing; and (2) they
      should provide explanatory power for these terms within nursing's disciplinary
      substance. Arguments are continued for a "within-the discipline" structure, a
      substantive and syntactical structure for the discipline of nursing that
      recognizes the centrality of biobehavioral processes in the practice of nursing
      [Gortner, IMAGE: J. Nurs. Scholarship 22, 101-105 (1990)].

PMID- 8288418
TI  - Nursing students' initial clinical experience: a phenomenological study.
AB  - Nursing students have revealed that one of the most anxiety-producing aspects of
      their clinical experience is the initial clinical experience. In order to help
      students through their initial clinical experience, faculty must first understand
      more fully the meaning of this experience for nursing students. A
      phenomenological study was conducted to explore the lived experience of nursing
      students' first clinical experience. Eighteen undergraduate nursing students
      described in writing an experience they had during their first day of clinical.
      Data were analyzed using Colaizzi's phenomenological method. Six theme clusters
      emerged: pervading anxiety, feeling abandoned, encountering reality shock,
      envisioning self as incompetent, doubting choices, and uplifting consequences.
      Implications for nurse educators are addressed.

PMID- 8288419
TI  - Ergonomic education for nursing students.
AB  - An educational package of common ergonomic training as well as behavioural
      training was implemented in nursing education. The teaching methods also had the
      aim of increasing students' awareness of the importance of total work environment
      for the prevention of back injuries. The experimental group was, on the whole,
      more pleased with their education than the control group. The experimental group
      judged their ability to analyse the work environment higher than the control
      group did. Observations in some practical work-tasks showed that students from
      the experimental group worked in physically more favourable positions with less
      strain on the body.

PMID- 8288420
TI  - A clinical application of the multiple sorting technique.
AB  - The interview technique is a common method of collecting data in human research.
      This paper provides an example of the use of the multiple sorting technique for
      structuring and analysing qualitative interviews. The technique is described
      around a recently completed study which explored practising nurses' perception of
      their work in a German hospital. A multiple sorting technique was employed to
      structure interviews with 11 nurses. Nursing tasks were sorted into categories
      and labelled by respondents. The frequencies with which each task was paired with
      all of the other tasks were calculated and this allowed us to produce a
      similarity matrix which was entered as input into a multidimensional scaling
      procedure (Smallest Space Analysis SSA-1). The SSA-1 procedure was used to
      analyse and interpret the data. The results of the analysis indicated that the
      nurses conceptualized their work into four separate domains including basic care
      skills, indirect care, technical skills and administration. The example of the
      multiple sorting technique described here shows how it is possible to develop an
      insight into the nurses' world in a structured yet flexible way.

PMID- 8288421
TI  - Energy fields nursing: a brief encounter of a unitary kind.
AB  - This paper explores the practical application of Martha Rogers' Science of
      Unitary Human Beings using a brief case study to illustrate the central concept
      of energy fields. Pattern manifestation appraisal and deliberative mutual
      patterning gave guidance for the care of a patient who had recently had a
      bilateral mastectomy. It is suggested that far from being a complicated and
      esoteric framework, the Science of Unitary Human Beings will have considerable
      impact on future nursing practice.

PMID- 8288422
TI  - Health status, health perceptions, and health behaviors of young adult women.
AB  - A descriptive, exploratory study of 76 young adult women enrolled in a women's
      health course at a large, midwestern university was undertaken to identify their
      current health status, health perceptions, and general health behaviors. Two
      groups of young adult females participated, nursing students (n = 38) and non
      nursing students (n = 38). The panel of young adult women in this study reported
      their health as good or excellent, viewed health as very important and generally
      used positive health practices. However, data revealed that the lifestyles of
      many respondents were not conducive to promoting or maintaining health. Negative
      health practices identified were drinking and driving, non-performance of self
      breast examinations, ineffective stress management strategies and poor dietary
      and exercise habits. No significant differences were noted between nursing and
      non-nursing students.

PMID- 8288423
TI  - Cognitive-behavioral techniques to reduce pain: a validation study.
AB  - The purpose of this study was to identify and validate specific activities
      considered important in the implementation of three non-pharmacologic pain
      management interventions--relaxation, distraction and guided imagery. Using a two
      round Delphi survey, nurses selected for their expertise in pain management were
      asked to validate definitions and activities considered important in the
      implementation of each of these strategies. Data were analyzed using a
      modification of Fehring's diagnostic content validity method. From this process,
      a list of activities for each intervention evolved that has implications for
      nursing research, practice and education.

PMID- 8288424
TI  - Social evaluation of health care versus personal evaluation of health states.
      Evidence on the validity of four health-state scaling instruments using Norwegian
      and Australian surveys.
AB  - In most of the cost-utility literature, quality-adjusted life-year (QALY) gains
      are interpreted as a measure of social value. Given this interpretation, the
      validity of different multi-attribute health-state scaling instruments may be
      tested by comparing the values they provide on the 0-1 QALY scale with directly
      elicited preferences for person trade-offs between different treatments
      (equivalence of numbers of different patients treated). Norwegian and Australian
      public preferences as measured by the person trade-off suggest that the EuroQol
      Instrument assigns excessively low values to health states. This seems to be even
      more true of the McMaster Health Classification System. The Quality of Well-being
      Scale appears to compress states toward the middle of the 0-1 scale. By contrast,
      the Rosser/Kind index fits reasonably well with directly measured person trade
      off data.

PMID- 8288425
TI  - Benefits and costs of recombinant human erythropoietin for end-stage renal
      failure: a review. Benefits and costs of erythropoietin.
AB  - Recombinant human erythropoietin is an efficacious therapy in treatment of the
      anemia of end-stage renal failure. However, the scale of impact on quality of
      life and medical care resources remains uncertain. By reviewing the literature we
      evaluate cost-effectiveness of recombinant human erythropoietin and show how
      previous studies may have implicitly overestimated cost-effectiveness.

PMID- 8288426
TI  - Revisiting the most informed consumer of surgical services. The physician
      patient.
AB  - Little is known about the consumption of medical and surgical services by the
      most informed consumer in the health care market: the physician-patient. Such
      knowledge should be important for the understanding of the role of information on
      consumption, supplier-induced demand, the doctor-patient relationship,
      unnecessary medical services, and the adequacy of professional practices to the
      renal health needs of the "ordinary patient." We measured by questionnaire the
      standardized consumption of seven common surgical procedures. Except for
      appendectomy, the age- and sex-standardized consumption for each of the common
      surgical procedures was always significantly higher in the general population
      than for the "gold standard" of physician-patients. The data suggest that (a)
      contrary to prior research, doctors have much lower rates of surgery than does
      the general population; and (b) in a fee-for-services health care market without
      financial barriers to medical care, less-informed patients are greater consumers
      of common surgical procedures.

PMID- 8288427
TI  - Hospital utilization reviews under field conditions: potential and improvements.
AB  - Hospital reviews based on an adaptation of Gertman and Restuccia's
      Appropriateness Evaluation Protocol were performed by acute care hospitals and
      the canton of Vaud (Switzerland) public health department in three settings
      during a six-month period in 1990-91. Interrater agreement between hospital and
      public health department reviewers was measured on 1,847 days of consecutively
      admitted patients during the last weeks of the reviews.

PMID- 8288428
TI  - The influence of health technology assessment on the diffusion of MRI in
      Australia.
AB  - A major assessment of magnetic resonance imaging (MRI) in Australia influenced
      the early use of this technology and informed policy decisions on future MRI
      services. However, the impact of the assessment, and of government policy, on the
      subsequent diffusion of MRI has been more modest, reflecting the limitations of
      the evaluation process in a complex health care system.

PMID- 8288429
TI  - Acquiring advanced technology. Decision-making strategies at twelve medical
      centers.
AB  - This study describes decision making regarding the acquisition of technology in
      12 major medical centers. The financial impact of a project was the most widely
      cited criterion of decision, but financial considerations were less important
      than either the impact of a technology on the quality of clinical care or its
      contribution to teaching and research. Rarely were criteria set out explicitly or
      in advance. Although exemplary models exist, the technology assessment process at
      most institutions is described as "political," "informal," or "ad hoc."

PMID- 8288430
TI  - Survival from localized breast cancer. Variability across trials and registries.
AB  - Age-specific (< 50, 50-69 years) 10-year survival proportions in four European
      trials for node-negative, Stage I and II breast cancer patients differ
      significantly. These patients, identified as having the same stage as localized
      breast cancer patients in the End Results Registry of the U.S. National Cancer
      Institute, had pooled survival proportions for the two age groups (0.713, 0.579)
      close to those of the registry (0.713, 0.607).

PMID- 8288431
TI  - The European Community's research projects in the field of health services.
AB  - Collaboration within the European Community (EC) over health problems and their
      possible solutions has progressed significantly during the past decade. The
      pursuit of appropriate choices among a variety of issues has resulted in a
      growing demand for comparable health data. EC efforts to coordinate the health
      services research of the member states in the fourth Medical and Health Research
      Program (1987-91) are discussed. Its contribution to the development of
      information relevant to the EC's health needs as well as financing, policies, and
      practices is outlined.

PMID- 8288432
TI  - Assessing technology assessment. Early results of the Quebec experience.
AB  - The Quebec Council on Health Care Technology Assessment was created in 1988. Its
      functions are to promote, support, and produce health care technology assessments
      and to advise the Minister of Health. An independent review of the council's
      first four years of operation was commissioned. The evaluation team concluded
      that the council showed very good results in terms of the scope, quality, and
      impact of its production and succeeded in establishing its credibility. However,
      the evaluation team suggested that the council adopt a more active strategy
      toward the promotion and diffusion of its reports. Some critical determinants of
      success of the Quebec experience in technology assessment are discussed.

PMID- 8288433
TI  - The usefulness of four methods of assessing the benefits of electrically
      adjustable beds in relation to their costs.
AB  - Ten picture cards, interviews, time logs, and the Klein-Bell ADL scale were
      useful in assessing the benefits of electrically adjustable beds to patients but
      not to caregivers. The mean cost per bed per year of US $346 seems, in relation
      to the benefits, to be a worthwhile investment for increasing patients' quality
      of life.

PMID- 8288434
TI  - Cost savings through technological change in the administration of antibiotics.
AB  - Once-daily antibiotics (ODAs) represent a technological change in hospital
      processes that can lead to substantial savings of scarce resources. In a three
      hospital prospective study, five antibiotics were administered to 58 patients
      suffering from infections classified by major body system. Savings ranged from
      10.9% to 38%, depending on hospital organization, method of delivery, and daily
      dose. Per-unit price proved a poor indicator of hospital cost, as variable
      delivery costs for labor and materials ranged from 11.6% to 39.5% of total costs.

PMID- 8288435
TI  - Report from the Australian Institute of Health and Welfare, Canberra, Health
      Technology Division. Perceptions of Australian Health Technology Assessments:
      report of a survey.

PMID- 8288436
TI  - Reports from the Canadian Coordinating Office for Health Technology Assessment
      (CCOHTA). Magnetic field strength issues in magnetic resonance imaging (MRI).

PMID- 8288437
TI  - Reports from the French Agence Nationale Pour le Developpement de l'Evaluation
      Medicale (ANDEM). Excimer laser in ophthalmology.

PMID- 8288438
TI  - Reports from the Swedish Council on Technology Assessment in Health Care (SBU).
      Evidence for health care technology assessment: a guide to searching the
      literature and interpreting the evidence.

PMID- 8288439
TI  - Report from the U.K. King's Fund Centre for Health Services Development. Medical
      audit: taking stock.

PMID- 8288440
TI  - Expression and function of an IgE-binding animal lectin (epsilon BP) in mast
      cells.
AB  - epsilon BP (IgE-binding protein) is a 31,000 M(r) protein originally identified
      in rat basophilic leukemia (RBL) cells. The protein is composed of two domains
      with the amino-terminal domain containing a highly conserved repetitive sequence
      and the carboxyl-terminal domain containing consensus sequences shared by other
      beta-galactoside-binding soluble lectins. The protein has wide tissue
      distribution, is found on cell surfaces and in extracellular milieu. By combined
      efforts from several research groups including ours a multifunctional nature of
      this lectin began to emerge. This review emphasizes the following characteristics
      of epsilon BP: (i) epsilon BP is secreted by cells such as macrophages; (ii) like
      many other lectins, epsilon BP functions at least bivalently; (iii) epsilon BP
      has specificity for distinct oligosaccharide structures that have a terminal
      galactose not masked by sialic acids; and (iv) in addition to binding IgE,
      epsilon BP binds to surfaces of various cell types via lectin-carbohydrate
      interaction. Importantly, epsilon BP binds to the IgE receptor on mast cells. We
      propose that epsilon BP can function as a modulatory protein on various cells by
      cross-linking critical cell surface glycoproteins. The proposed action of epsilon
      BP on mast cells is presented as a model.

PMID- 8288441
TI  - Photofrin, but not benzoporphyrin derivative, stimulates hematopoiesis in the
      mouse.
AB  - This report describes the effects of the porphyrin photosensitizers, Photofrin
      and benzoporphyrin derivative (BPD) on the immunohematopoietic system of normal
      and immunosuppressed DBA/2 mice in the absence of activating light. Photofrin (10
      and 25 mg/kg) significantly increased in vitro colony formation by cells of the
      granulocyte-macrophage lineage in the spleen and bone marrow. Splenic
      hypercellularity, splenomegaly and elevated levels of blood leukocytes were
      observed in these mice 7 days following Photofrin injection. Evidence that
      Photofrin influenced the lymphohematopoietic compartment was suggested by a
      significant increase in blood lymphocytes and a population of spleen cells
      identified by a monoclonal antibody (LR-1) reactive with mouse splenic B
      lymphocytes. Proliferative responses of spleen cells from Photofrin-treated mice
      to sub-optimal concentrations of Con A were greater than that observed for
      controls. However, spleen cell responses to LPS were unaltered by Photofrin
      administration. In contrast, BPD (10 mg/kg) did not alter any of the
      immunohematopoietic parameters studied. When Photofrin was administered to mice
      treated with the myeloablative agent 5-FU there was a significant acceleration in
      the recovery of total blood leukocyte and spleen cell numbers, relative to the
      controls. These studies demonstrate that, in addition to its previously
      documented activities as a photosensitizer, Photofrin can exert stimulatory
      effects upon murine hematopoiesis.

PMID- 8288442
TI  - A histamine derivative increases intracellular calcium mobilization and oxidative
      metabolism in HL-60 cells.
AB  - Past work in our laboratory has shown that a derivative of histamine, histamine
      trifluoromethyl-toluidide (HTMT), has surprising tissue specificity on
      lymphocytes and can produce remarkable immunosuppression. This study focuses on
      the effects of HTMT on Ca2+ mobilization and oxidative metabolism in
      undifferentiated and DMSO-differentiated HL-60 cells. HTMT caused two phases of
      increases in intracellular calcium concentrations ([Ca2+]i) in HL-60 cells. The
      responses were dose dependent, with similar EC50 values (1.7 x 10(-5) M for
      undifferentiated and 1.5 x 10(-5) M for differentiated cells). The increase in
      [Ca2+]i in differentiated cells was much greater than in undifferentiated cells.
      The maximum responses were observed after the undifferentiated cells were
      incubated with DMSO for 7 days. The increase in [Ca2+]i induced by HTMT in both
      types of cells was competitively antagonized by high concentrations of histamine
      but not by classic histamine receptor antagonists (H1, H2, or H3). The inhibitory
      effects of histamine on [Ca2+]i accumulation in differentiated cells were
      partially reversed by histamine H2 receptor antagonist ranitidine, whereas in
      undifferentiated cells, the effects of histamine on Ca2+ mobilization were not
      affected by ranitidine. Other cAMP elevating agents did not inhibit increases in
      [Ca2+]i in undifferentiated cells but did affect [Ca2+]i in differentiated cells.
      The enhanced response in [Ca2+]i mobilization after differentiation of HL-60
      cells appeared to be the result of an increase in the expression/function of
      receptors for HTMT. One interesting feature of this regulation was the fact that
      cAMP per se did not regulate HTMT induced Ca2+ mobilization in undifferentiated
      cells but inhibited the mobilization in differentiated cells. HTMT caused the
      generation of reactive oxygen species in both undifferentiated and differentiated
      HL-60 cells as measured by chemoluminescence and the levels of generation
      correlated with the mobilization of [Ca2+]i. In addition, the EC50s for the HTMT
      induced calcium mobilization and the generation of reactive oxygen species were
      similar, as was the case for histamine induced inhibition (Ki) in both cell
      types. The data imply a second messenger role for Ca2+ in HTMT induced neutrophil
      activation.

PMID- 8288443
TI  - Polyclonal anti-idiotypes induce specific anti-saxitoxin antibody responses.
AB  - Polyclonal BALB/C mouse and New Zealand White rabbit anti-idiotypic antibodies
      were raised by immunization with a protein G-purified burro anti-saxitoxin IgG
      antibody preparation. Following absorption of non-anti-idiotype reactivity,
      murine and rabbit IgG were purified by protein A chromatography and used to
      immunize BALB/C mice for the induction of anti-saxitoxin antibody responses.
      Unconjugated BALB/C anti-idiotypes did not induce significant anti-saxitoxin
      reactivity in BALB/C mice, even after repeated immunizations. However, BALB/C
      mice immunized with purified BALB/C anti-idiotypes conjugated to keyhole limpet
      hemocyanin, or with purified, unconjugated rabbit anti-idiotypes, as aluminum
      hydroxide precipitates, induced significant and specific anti-saxitoxin immune
      responses. Saxitoxin, a sodium channel blocker, can protect cells treated with
      veratridine and ouabain, whose respective actions are to open sodium channels and
      to block the activity of Na/K-ATPase. The anti-idiotype-induced anti-saxitoxin
      antibodies inhibited saxitoxin from protecting against cell death induced by
      veratridine and ouabain treatment. These and other published experimental results
      strengthen the concept of anti-idiotype-based vaccines in eliciting protective
      immunity against a variety of low molecular weight, nonproteinaceous biological
      and chemical toxins, whose extreme toxicity does not allow their use as safe
      immunogens.

PMID- 8288444
TI  - Synergic stimulation of arabinosylcytosine induced apoptosis in mouse thymocytes
      by cyclic AMP.
AB  - Previous studies demonstrated that arabinosylcytosine (ara-C) induced
      internucleosomal DNA fragmentation and cell death in mouse thymocytes and that
      those were inhibited by 1-(5-iso-quinoline-sulfonyl)-2-methylpiperazine
      hydrochloride, an inhibitor of protein kinases. In the present study, we examined
      the relationship between the DNA fragmentation induced by ara-C and that by
      agents which activate intracellular signaling and induce apoptosis in mouse
      thymocytes. 12-O-tetradecanoyl 13-acetate, a phorbol ester capable of activating
      protein kinase C or A23187, a calcium ionophore, had no effect on ara-C induced
      DNA fragmentation. However, ara-C induced DNA fragmentation was synergistically
      enhanced by cAMP and cAMP receptor agonists. Ara-C inhibited the incorporation of
      choline into the acid soluble and lipid fractions, and cAMP enhanced this
      inhibition, suggesting that ara-C metabolites interfere with membrane
      phospholipid metabolism, partly evoking a certain cellular signaling for
      apoptosis and interacting with cAMP-evoked signaling.

PMID- 8288445
TI  - Anti-stomach serum induces contraction of isolated smooth muscle cells from
      gastric antrum.
AB  - In this work, we investigated the ability of anti-tissue sera to cause
      contraction of smooth muscle cells (SMC) in vitro. Therefore, we compared the
      effects of a horse immune serum raised against hog gastric tissue (SER 292), of
      its globulin fraction (SER 292 globulin), and of its IgG fraction (SER 292 IgG),
      on concentration of isolated SMC from the gastric antrum of the rabbit. Our
      results showed that SER 292 IgG induced a dose-dependent contraction of SMC with
      a higher potency than SER 292 globulin and SER 292. Preincubation of SER 292
      globulin with anti-F(ab')2 but not with anti-Fc reduced the contractile activity
      of this anti-tissue serum. A serum raised against reticulo-endothelial system
      (SER 108) as well as a non immune serum (SENI) did not show any contractile
      activity. Our data provide evidence that SER 292 interacts with plasma membrane
      of SMC through its F(ab')2 fragments. Withdrawal of extracellular Ca2+ caused a
      significant reduction of the contractile effect induced by SER 292 IgG. When 45
      Ca influx was measured, SER 292 IgG induced a specific and significant 45 Ca
      uptake which was blocked by pinaverium, a 'L-type' calcium channel blocker. These
      findings tend to show that contraction of SMC induced by SER 292 IgG involves an
      increase of intracellular Ca2+ concentration due in part to an influx of external
      Ca2+ via plasma membrane Ca2+ channels sensitive to 'L-type' channel blockers.

PMID- 8288446
TI  - Tamm-Horsfall urinary glycoprotein enhances monokine release and augments
      lymphocyte proliferation.
AB  - Tamm-Horsfall glycoprotein (THG) purified from pregnancy urine was found to
      stimulate normal human mononuclear cell (MNC) proliferation at a concentration
      greater than 10 micrograms/ml. This stimulation was non-specific because the
      percentage of B and T cell subpopulations including CD20, CD3, CD4, CD8 and
      CD4/CD8 ratio was not changed by THG. THG not only bound to human mononuclear
      cells but depolarized the membrane potential, increased 22Na+ uptake and enhanced
      the expression of IL-2R and HLA-class II antigens on these cells. The
      concentrations of sIL-2R, sCD4 and sCD8 in the THG-stimulated MNC culture
      supernatants were significantly increased compared with control supernatants. In
      addition, overnight incubation of THG (5-50 micrograms/ml) with MNC dose
      responsively enhanced the syntheses of IL-1 beta, IL-6 and TNF-alpha by
      monocytes, with a maximal effect at 25 micrograms/ml. This monokine releasing
      activity of THG could be neutralized by a specific antibody against THG. When
      monocytes/macrophages were depleted from mononuclear cells by incubating with
      lysosomotropic methyl ester of L-leucine, THG retained the capability of
      stimulating lymphocytes proliferation but to a lesser degree. These results
      suggest that urinary THG activates monocytes to synthesize large amount of
      monokines through its membrane effect. The released monokines subsequently
      stimulate lymphocytes expressing IL-2R and HLA-class II antigens and finally lead
      to cell proliferation.

PMID- 8288447
TI  - William Withering, MD, FRS, FLS (1741-1799): a country doctor and his role in
      medicine and science.

PMID- 8288448
TI  - Routine withholding of digitalis for heart rate below 60 beats per minute:
      widespread nursing misconceptions.
AB  - OBJECTIVE: To describe the nursing practice of withholding digitalis solely on
      the basis of a heart rate less than 60 beats/min and to determine the rationale
      for this practice. DESIGN: Non-randomized survey. SETTING: Five hospitals in a
      midwestern metropolitan area, ranging from affiliates of a university medical
      center to a private community-based hospital. SUBJECTS: Two hundred twelve
      nurses, 53% from critical care units, 19% from step-down units, and 28% from
      nonmonitored units). RESULTS: Eighty-one percent of respondents either withheld
      digitalis unnecessarily or administered the drug without correctly indicating why
      they did so. Nurses with CCRN certification were more likely to answer correctly
      than those who were not certified (p = 0.0001). Categories for incorrect
      rationale were (1) incorrect understanding of the drug's mechanism of action
      (46%), (2) deference to physician's decision-making (28%), (3) adherence to
      hospital policy (18%), and (4) adherence to guidelines taught in nursing school
      (6%). CONCLUSIONS: The results document the need to correct widespread
      misconceptions regarding the mechanism of action for digitalis and subsequent
      nursing practice.

PMID- 8288449
TI  - The use of central nervous system manifestations in the early detection of
      digitalis toxicity.
AB  - Cardiac glycosides have been used therapeutically for more than 3000 years. They
      have been the treatment of choice for congestive heart failure for many decades,
      and recently their clinical utility has been redefined. Despite increased
      telemetry and development of a sensitive radioimmune assay of serum digoxin
      levels and the availability of digoxin immune Fab fragments (Digibind) to treat
      digitalis-induced life-threatening dysrhythmias, toxicity remains a serious and
      common problem. A body of literature, old and new, speaks to the clear but
      potentially unrecognized role that digitalis-induced central nervous system
      symptoms can play in the early detection and management of digitalis toxicity.

PMID- 8288450
TI  - Full-disclosure monitoring: a concept that will change the way arrhythmias are
      detected and interpreted in the hospitalized patient.
AB  - Conventional methods of detecting and documenting arrhythmia in the hospitalized
      patient are inadequate. A system of full-disclosure monitoring has been expanded
      from its roots in Holter monitoring to real-time telemetry. This archiving system
      stores 24 hours of electrocardiogram (ECG) tracing per patient in computer memory
      and prints 60 minutes (one minute per line, 60 lines per page) of ECG hourly.
      This technique eliminates the fear of missing ventricular tachycardia, heart
      block, or automatic implantable cardioverter defibrillator discharges and ensures
      that onsets and terminations of runs are captured. Documentation is facilitated
      by the use of a laser printer that makes standard-sized tracings. The
      retrospective capability of full disclosure monitoring aids in correlating
      symptoms to ECG changes and serves as a tool for quality control, bed
      utilization, and research.

PMID- 8288451
TI  - Offset potential of commercial ECG electrodes.
AB  - OBJECTIVE: To determine the offset potential characteristics of commercially
      available disposable electrocardiograph (ECG) electrodes. DESIGN: Descriptive.
      SETTING: Laboratory. SAMPLE: Four hundred twenty-eight (214 pairs) disposable ECG
      electrodes representing 11 manufacturers/types. OUTCOME MEASURES: Direct current
      offset potential. RESULTS: The maximum offset potential for any electrode pair of
      a given type ranged from 0.2 mV to 21.6 mV. Of the 11 types of electrodes
      studied, three had a mean offset potential of < 0.1 mV and one type had a mean
      offset potential of > 1.0 mV. CONCLUSIONS: Although all of the ECG electrodes
      studied meet applicable standards, the differences found may be important when
      measuring biologic signals other than the electrocardiogram.

PMID- 8288452
TI  - Internal cardioverter defibrillator device discharge: experiences of patients and
      family members.
AB  - PURPOSE: The purpose of the study was to describe sensations, symptoms, and
      experiences of internal cardioverter defibrillator (ICD) activations from the
      perspective of patients and a member of their family. METHODS: A prospective,
      descriptive study with qualitative and quantitative measures was used. Patients
      with an ICD returned a device activation form within 24 hours after receiving a
      shock and both patient and family members participated in interviews at 1, 3, and
      6 months after ICD implantation. SAMPLE: Twenty-two patients with ICD (two women,
      20 men) between the ages of 24 to 72 years (mean 56.5 years) and one family
      member per patient participated. Family members ranged in age from 43 to 67 years
      (mean 52.6 years) and were primarily spouses. RESULTS: The most distressing
      aspects of receiving a shock were lack of warning, multiple shocks, and
      progressively increased sensations with multiple shocks. Mean shock intensity was
      ranked 5.44 on visual analog scale with a range of 0 to 10. The most frequently
      reported symptoms and sensations were generalized nervousness and terror/fear.
      Dizziness, general weakness, nausea and vomiting, palpitations, and chest
      soreness were also noted. IMPLICATIONS: Nursing interventions related to
      education of patients with an ICD and their families can incorporate knowledge of
      these experiences to facilitate anticipatory guidance and strengthen preparation
      of both the patient and family member for ICD device discharge. Further research
      as device technology evolves is warranted.

PMID- 8288453
TI  - Recurrent unexplained syncope: the role of head-upright tilt table testing.
AB  - Recurrent episodes of sudden unexplained syncope are a common complaint of
      patients referred to health care professionals for evaluation. Traditional
      evaluations are both time consuming and expensive and leave many patients without
      a diagnosis. Although vasovagally mediated episodes of hypotension and
      bradycardia have been thought to be a common cause of unexplained syncope, this
      was traditionally a diagnosis of exclusion. Head-upright tilt table testing has
      recently emerged as a valuable method for confirming the diagnosis of vasovagal
      syncope and has allowed a better understanding of this phenomena. This article
      reviews the pathophysiology of vasovagal syncope, the use of head-upright tilt
      table testing in its diagnosis, and potential therapies used to prevent
      recurrences.

PMID- 8288454
TI  - A comparison of resuscitation skills of qualified general nurses and ambulance
      nurses in The Netherlands.
AB  - OBJECTIVE: To investigate the ability of qualified general nurses to perform
      cardiopulmonary resuscitation and to compare these skills with those of a group
      of ambulance nurses. DESIGN: Cross-sectional assessment of practical
      cardiopulmonary resuscitation skills. SUBJECTS: 141 Dutch general nurses. OUTCOME
      MEASURES: The practical skills were tested with six primary variables that
      describe the quality of cardiopulmonary resuscitation techniques in a training
      situation. A total score on the skills was computed based on a predefined scoring
      system. RESULTS: The percentage of general nurses who were able to achieve a pass
      score (i.e., the total score did not exceed 15 penalty points) was 6.4 percent.
      The average score was 37.8 penalty points. Eighty-eight percent of the ambulance
      nurses achieved a pass score. The average number of penalty points was 10.5.
      CONCLUSIONS: The practical skills in cardiopulmonary resuscitation are
      insufficient in the majority of this sample of general nurses in The Netherlands.
      The findings of this study should be used as a base to design an optimal form and
      content of an educational re-instruction program. We expect that a considerable
      improvement could be achieved by more frequent cardiopulmonary resuscitation re
      instruction.

PMID- 8288455
TI  - Hyperventilation in the head-injured patient: an effective treatment modality?
AB  - Mortality and poor functional outcomes remain major problems in patients who
      experience a severe head injury. Cerebral injury from high intracranial pressure
      contributes to the head injury. A basic postulate in the care of the head-injured
      patient is the prevention of secondary cerebral damage through the management and
      prevention of high intracranial pressure. Hyperventilation, once an established
      intervention in the treatment and control of intracranial hypertension in
      patients with severe neurologic injury, has become increasingly controversial.
      This article reviews (1) the normal physiology of the brain, (2) the
      pathophysiologic changes that occur during head injury, and (3) the theoretical
      rationale of hyperventilation and its interaction with nursing care. A case study
      is presented to highlight how the patient's response to a routine nursing
      procedure, endotracheal suctioning, may change as a result of hyperventilation.

PMID- 8288456
TI  - Reliability and validity of spirometry measurements in a paperless home
      monitoring diary program for lung transplantation.
AB  - OBJECTIVE: To demonstrate that home spirometry measurements are reliable and
      valid and can be used as part of a home measurement monitoring system by lung
      transplant recipients. DESIGN: Longitudinal, observational. SETTING: University
      medical center. SUBJECTS: Eighteen patients who have undergone lung
      transplantation; age range was 24 to 63 years (mean of 49.5 years). OUTCOME
      MEASURES: Reliability and validity of forced expiratory volume at 1 second (FEV1)
      and forced vital capacity (FVC). INTERVENTION: Recording of spirometry, vital
      signs, and symptom measures at home each day by use of a paperless electronic
      diary/spirometer instrument. RESULTS: Day-to-day variability as measured by the
      standard deviation ranged from 0.013 L to 0.202 L for FVC and 0.015 L to 0.117 L
      for FEV1. The correlation between the two best forced expiratory maneuvers on any
      given day was 0.98 for both FVC and FEV1, with percent differences between the
      measurements of 2% for FVC and 3% for FEV1. The correlation between measurements
      performed in the pulmonary function laboratory and measurements done by the
      patient at home on the same day was 0.94 for FVC and 0.99 for FEV1. CONCLUSIONS:
      This evaluation demonstrated that home measurements are both reliable (i.e.,
      repeatable) and valid when compared with the "gold standard" of the pulmonary
      function laboratory. The home monitoring program has been well accepted by
      patients, is easy to use, and provides data comparable to that collected during
      clinic visits.

PMID- 8288457
TI  - Predictors of burnout in critical care nurses.
AB  - OBJECTIVE: To develop a conceptual path model to explain the effects of a set of
      personal and occupational independent variables and the dependent variables of
      situational stress, job stress, job satisfaction, and job motivation on burnout
      among critical care nurses. DESIGN: A prospective descriptive study using a
      conceptual path model. SETTING: Nine hospitals in the northeastern, northwestern,
      north central, and southern regions of Florida. SAMPLE: Three hundred female
      critical care nurses employed in the nine hospitals who had worked full-time for
      at least 3 months. INSTRUMENTS: Subjects were administered a demographic and work
      survey instrument, the Daily Hassles Instrument, the Psychological Hardiness
      Test, the Job Diagnostic Inventory, and the Maslach Burnout Inventory. RESULTS:
      Path analysis of a burnout model resulted in a causal progression of situational
      stress, job stress, job satisfaction, and emotional exhaustion (which is a
      component of burnout). The results showed that commitment to career, health
      difficulties, psychologic hardiness, work load satisfaction, dealing with others
      at work, job security, and job satisfaction had a significant effect on emotional
      exhaustion. CONCLUSION: Seven variables had a significant effect on emotional
      exhaustion, which is a component of burnout, and explained 34% of the variance.
      The three most significant effects on emotional exhaustion were commitment to
      career, dealing with others at work and job satisfaction. Health difficulties,
      psychologic hardiness, work load satisfaction, and job security had a modest
      effect on emotional exhaustion.

PMID- 8288458
TI  - Two instruments to measure interdisciplinary bioethical decision making.
AB  - OBJECTIVE: To develop and test two instruments measuring decision making about
      level of aggressiveness of intensive care unit (ICU) patient care. Decisions
      about Aggressiveness of Patient Care (DAC) measures care providers' general
      perceptions about decision making. Decisions about Aggressiveness of Patient Care
      for Specific Patients (DAC[SP]) measures perceptions in specific situations.
      DESIGN: Two-phase psychometric instrument evaluation. SETTING: Phase I,
      nationally mailed questionnaire. Phase II, northeastern medical center medical
      ICU. SUBJECTS: Phase I, 22 ICU nurse and physician experts. Phase II, 35 medical
      ICU staff nurses and eight medical resident physicians. OUTCOME MEASURE:
      Psychometric properties of instruments. RESULTS: Content validity of both tools
      was supported by their development from the literature and by the experts. Face
      validity was supported by the experts, staff nurses, and medical resident
      physicians. Both instruments had variance in responses, internal consistency
      reliability (r = 0.53, r = 0.73) and, test-retest reliability (r = 0.73).
      CONCLUSION: These instruments may enrich our understanding of how care providers
      make bioethical decisions for ICU patients. Such understanding could assist with
      development of interventions to increase collaborative interdisciplinary decision
      making, leading to increased care provider satisfaction and better patient
      outcomes.

PMID- 8288460
TI  - Adenosine for the treatment of paroxysmal supraventricular tachycardia in a
      pediatric patient: a case study.

PMID- 8288459
TI  - Changes in the pharmacotherapy of CPR.
AB  - The objective of this study was to review current changes in the pharmacologic
      management of cardiac arrest (ventricular fibrillation, pulseless ventricular
      tachycardia, asystole, and electromechanical dissociation) as put fourth by the
      American Heart Association's 1992 Guidelines for Cardiopulmonary Resuscitation
      and Emergency Cardiac Care. We concluded that the 1992 Guidelines provide a
      reference base for all clinicians involved in emergency cardiac care. The newly
      revised recommendations are classified on the basis of the true clinical merit of
      the intervention, for example, an intervention that has been proved effective
      (i.e., high-dose epinephrine) versus one that is possibly effective (i.e., high
      dose epinephrine). The preferred intravenous fluid to be used in resuscitation is
      saline solution or lactated ringers solution because of possible adverse
      neurologic outcomes seen with dextrose-containing fluids. The dose of all drugs
      administered via the endotracheal route should be 2 to 2.5 times the intravenous
      dose. Modifications in the dose or dosing interval have been recommended for
      epinephrine, atropine, lidocaine, bretylium, and procainamide during
      cardiopulmonary resuscitation. Options for high-dose epinephrine therapy are
      offered, but neither recommended or discouraged. Magnesium sulfate has been added
      for the management of torsades de points, severe hypomagnesemia, or refractory
      ventricular fibrillation. The maximum total dose of atropine in the treatment of
      asystole and electromechanical dissociation has been increased from 2 mg to 0.04
      mg/kg. The use of sodium bicarbonate should be limited to the treatment of
      hyperkalemia, tricyclic antidepressant overdose, overdoses requiring urinary
      alkalinization, or preexisting bicarbonate sensitive acidosis.

PMID- 8288461
TI  - An infection control educational needs assessment for ICU personnel.

PMID- 8288462
TI  - Spotlight article: quinidine enhances digitalis toxicity at therapeutic serum
      digoxin levels. (Mordel A, Halkin H, Zulty I, Almog S, Ezra D. Clin Pharm Ther
      1993;53:457-62).

PMID- 8288463
TI  - [Women with rupture of the sphincter--a literature and questionnaire study].

PMID- 8288464
TI  - [Women's experience of being a gynecological patient staying in the same
      environment as newly-delivered mothers and newborn infants].

PMID- 8288465
TI  - [Midwifery Day--from idea to reality].

PMID- 8288467
TI  - [Preventive work pays out--both human and economic aspects].

PMID- 8288468
TI  - More on diagnosis of canine borreliosis.

PMID- 8288469
TI  - Bovine spongiform encephalopathy.

PMID- 8288470
TI  - Early-age neutering, an "uncontrolled experiment".

PMID- 8288471
TI  - Current understanding of Borrelia burgdorferi infection, with emphasis on its
      prevention in dogs.

PMID- 8288472
TI  - Variety, the spice of industrial veterinary medicine.

PMID- 8288473
TI  - What is your diagnosis? Congenital elbow luxation with avascular necrosis of the
      femoral head, pathologic fracture of the femoral neck and bilateral medial
      luxation of the patellas in a dog.

PMID- 8288475
TI  - A veterinarian's duty regarding tests.

PMID- 8288474
TI  - Animal behavior case of the month. A breakdown in working performance, or
      burnout, was observed in a dog used in searches for explosives.

PMID- 8288476
TI  - Neonatal toxoplasmosis in littermate cats.
AB  - Toxoplasmosis was diagnosed histologically in 9 kittens and 1 queen from 5
      liters. In litter 1, four 3-month-old Siamese kittens and the queen were
      affected. The queen died of generalized toxoplasmosis, and her kittens died or
      were euthanatized 20, 22, or 28 days later. In litter 2, two of 3 Abyssinian 4-
      and 4.5-month-old kittens died of toxoplasmosis. In litter 3, an Abyssinian,
      delivered by cesarean section, became ill 17 days after delivery, and died 2 days
      later because of toxoplasmic hepatitis and pneumonia. In litter 4, three kittens,
      approximately 1 month old, were shedding Toxoplasma gondii-like oocysts, and the
      organism was identified histologically in tissues of 1 of them. In litter 5, one
      3-week-old kitten out of 4 became ill. Toxoplasma gondii-like oocysts were found
      in feces and T gondii organisms were found in histologic sections of tissues.

PMID- 8288477
TI  - Isolation of Leptospira interrogans serovar grippotyphosa from the skin of a dog.
AB  - Leptospira interrogans serovar grippotyphosa was isolated from the skin of a 14
      year-old male dog with deteriorating health. Necropsy revealed numerous lesions
      characteristic of aged dogs, but no evidence of acute hepatitis or nephritis,
      which are common features of pathogenic Leptospira infections. Antibody to
      Leptospira was not detected in the dog's serum by microagglutination. Leptospires
      grew slowly in Barbour-Stoenner-Kelly medium, a medium commonly used to isolate
      Borrelia, but then grew abundantly in Tween 80-bovine albumin leptospire medium.
      The isolate was pathogenic to a hamster and was identified by microagglutination
      and restriction endonuclease analysis.

PMID- 8288478
TI  - Estradiol-17 beta-secreting adrenocortical tumor in a ferret.
AB  - Severe generalized alopecia and marked vulvar enlargement were observed in a 5
      year-old spayed ferret with high serum estradiol concentrations. A neoplastic
      left adrenal gland was removed. Staining of the neoplastic cells for estradiol
      was demonstrated by use of immunohistochemistry. Clinical findings in this ferret
      were typical of adrenal-associated endocrinopathy, a syndrome characterized by
      increased secretion of adrenocortical hormones by hyperplastic or neoplastic
      adrenal glands.

PMID- 8288479
TI  - Histologically confirmed clinical toxoplasmosis in cats: 100 cases (1952-1990).
AB  - Tissue sections from 119 cats that died or were euthanatized (1952-1990) because
      of toxoplasmosis-like illness were reexamined for Toxoplasma gondii by direct
      microscopy and immunohistochemical staining with anti-T gondii serum. Clinical
      and pathologic data from 100 of these cats with histologically verified
      toxoplasmosis were then analyzed. Of these 100 cats, 36 were considered to have
      generalized toxoplasmosis, 26 predominantly pulmonary lesions, 16 abdominal, 2
      hepatic, 1 pancreatic, 1 cardiac, 2 cutaneous, 7 neurologic, and 9 had neonatal
      toxoplasmosis. In 14 cats, concurrent microbial infections or other maladies were
      seen. Cats were 2 weeks to 16 years old (median, 2 years; mean, 4 years). Sixty
      five cats were males and 34 were females; sex was not recorded for 1 cat. Of 67
      cats that had rectal temperatures recorded, 49 (73%) had fever (40.0 to 41.7 C).
      Dyspnea, polypnea, and signs of abdominal discomfort were frequently observed.
      Toxoplasmosis had been confirmed antemortem in 8 cats; 4 had a serum antibody
      titer to T gondii of > or = 1:1,024; and T gondii had been found in cytologic
      evaluation of tracheal aspirates from 2 cats and pleural fluid from 1 cat, as
      well as in a biopsy specimen of a mesenteric lymph node from another. Of the 15
      cats with T gondii serum-antibody titers determined by the Sabin-Feldman dye
      test, 6 had no antibody detected in 1:4 dilution of their serum. Indirect
      fluorescent antibody titers were found in 10 of 10 cats' sera tested. Forty-one
      eyes from 27 of the cats were examined microscopically. Twenty-two of the 27 cats
      (81.5%) had evidence of intraocular inflammation in one or both eyes. Multifocal
      iridocyclochoroiditis was the most common lesion and was seen in 18 (81.8%) of
      the cats with ophthalmitis. The ciliary body was the most often severely affected
      portion of the uvea. Of the 22 cats with ocular toxoplasmosis, T gondii was found
      in eyes of 10. Toxoplasma gondii was found in the retina of 5 cats, the choroid
      of 2, the optic nerve of 1, the iris of 3, and the ciliary body of 4. Toxoplasma
      gondii was identified in 80% of 55 brains, 70.0% of 90 livers, 76.7% of 86 lungs,
      64.4% of 45 pancreata, 62.7% of 59 hearts, 45.8% of 72 spleens, 41.5% of 65
      intestines, 17.7% of 61 kidneys, and 60.0% of 30 adrenal glands.

PMID- 8288480
TI  - Seasonal flank alopecia in boxers and Airedale terriers: 24 cases (1985-1992).
AB  - Clinical and histologic features of seasonal flank alopecia in 12 Airedale
      Terriers and 12 Boxers were reviewed. Most of the affected dogs were spayed
      females; however, sexually intact females as well as sexually intact and neutered
      male dogs with the disease were identified. Mean (+/- SD) age of onset was 3.6 +/
      2.4 years.

PMID- 8288481
TI  - Granulomatous enteritis and cutaneous arteritis in a horse.
AB  - A 5-year-old Quarter Horse mare was examined because of weight loss of 2 months'
      duration. The horse was anemic and in poor body condition, and had several areas
      of cutaneous ulceration, including areas on the muzzle and distal portion of the
      limbs. Histologic examination of a rectal mucosa biopsy specimen revealed a
      lymphoplasmacytic infiltrate in the lamina propria mucosa. Results of a glucose
      absorption test were suggestive of malabsorption. Histologic examination of a
      biopsy specimen from the cutaneous lesions revealed pronounced arteritis, and
      weak, patchy immunofluorescent staining for immunoglobulins at the basement
      membrane. The horse was treated with prednisone, but did not improve, so the
      horse was humanely destroyed. Necropsy revealed granulomatous enteritis. This
      case identified an unusual combination of clinical problems and suggests further
      evidence for similarities between equine granulomatous enteritis and regional
      enteritis in human beings.

PMID- 8288482
TI  - Effect of intrauterine antimicrobial treatment in reducing calving-to-conception
      interval in cows with endometritis.
AB  - A prospective clinical trial was conducted on 2 large dairies in the San Joaquin
      Valley of California to determine whether a single intrauterine infusion with
      procaine penicillin G or oxytetracycline reduced the calving-to-conception
      interval in cows with endometritis. Cows with endometritis were randomly assigned
      to a treatment or a control group. The uterus of treated cows on 1 dairy was
      infused with 0.8 to 1.0 million U of procaine penicillin G in 40 ml of sterile
      water, and the uterus of treated cows on the other dairy was infused with 500 mg
      of oxytetracycline in 20 ml of sterile water, both of which were typical doses
      used on dairies in the area. A difference was not observed in the cumulative
      proportion of cows remaining nonpregnant between 87 penicillin-treated and 77
      control cows on the 1 dairy (P = 0.356), or between 74 oxytetracycline-treated
      and 62 control cows on the other dairy (P = 0.174). Results suggest that routine
      infusion of antibiotics to treat endometritis, as commonly practiced, may not be
      efficacious.

PMID- 8288483
TI  - Acute myelomonocytic leukemia in a calf.
AB  - In a 2-month-old crossbred calf with paraplegia, results of neurologic evaluation
      were suggestive of a spinal cord lesion caudal to L3. The calf bled from the
      blood sampling site for an extended period after venipuncture. Leukocytosis,
      anemia, and thrombocytopenia were observed. The leukocytes were predominantly
      atypical blast cells. Postmortem examination revealed petechial hemorrhages
      throughout the internal organs. Bone marrow was pale tan, with no red marrow
      seen. Atypical leukocytes were diffusely distributed throughout the body, with
      penetration of the spinal cord and spinal roots, particularly in the lumbar
      region. Atypical leukocytes stained positively for alpha-naphthyl acetate
      esterase and chloracetate esterase, and stained with Sudan black B. Atypical
      leukocytes expressed class-1 and class-2 major histocompatability antigens, but
      did not express specific T-, B-, or null-cell surface antigens. The final
      diagnosis was myelomonocytic leukemia. Differential diagnosis of leukemia in
      calves should include myelogenous leukemia, and requires use of various
      techniques to make a definitive diagnosis.

PMID- 8288484
TI  - Review of foodborne outbreak of Escherichia coli O157:H7 infection in the western
      United States.

PMID- 8288485
TI  - Neuroendocrine cells in the human prostate gland.

PMID- 8288486
TI  - Cell proliferation in the dorsal and lateral lobes of the rat prostate during
      postnatal development.
AB  - We have shown previously that cell proliferation occurs throughout the ducts of
      the rat ventral prostate during its postnatal development. Our objectives herein
      were to identify and quantify proliferating cells in the dorsal and lateral
      lobes, to quantify DNA synthetic activity in the distal and proximal segments of
      these lobes, and to compare the results obtained to the results of our previous
      studies of the ventral lobe. [3H]-Thymidine, administered in vivo, was
      incorporated into both the distal and proximal segments of day 10-60 rat dorsal
      and lateral prostates. Quantitative analyses of autoradiographs revealed that the
      percentages of labeled cells in the distal and proximal segments of the dorsal
      and lateral lobes were not significantly different at days 45 and 60, and they
      were only slightly (though significantly) different at days 10 and 20.
      Biochemical analyses of [3H]-thymidine incorporation similarly revealed no
      significant differences in the distal and proximal segments at days 45 and 60,
      and only small differences at days 10 and 20. The results of analyses of mitotic
      figures were consistent with the results of autoradiographic analyses, showing
      clearly that cell proliferation occurs throughout the rat dorsal and lateral
      prostates. These results show for the first time that cell proliferation occurs
      throughout the dorsal and lateral lobes, strikingly reminiscent of the
      proliferation pattern that we reported previously for the ventral lobe.

PMID- 8288487
TI  - Metabolic studies on the rabbit corpus cavernosum.
AB  - Erectile function (erection and detumescence) involves the complex interaction of
      direct neuronal stimulation of corporal smooth muscle, neurohumoral release of
      specific endothelial contractile and relaxant factors, and secondary modulation
      by a variety of putative neuropeptides and vasoactive modulators. The net result
      is a rapid and sustained relaxation of the smooth muscle elements during erection
      and contraction of the smooth muscle during detumescence. Proper function of the
      corporal tissue is dependent upon cellular metabolism of glucose and the
      generation of cellular energy in the form of high energy phosphates. The current
      study characterizes the following metabolic parameters of the rabbit corpus
      cavernosum: Tissue concentrations of creatine phosphate (CP), ATP, ADP, and AMP;
      maximal rate of glucose metabolism to lactic acid and CO2; and activities of the
      enzymes creatine kinase (CK), citrate synthase, and malate dehydrogenase. For
      comparative purposes only, bladder smooth muscle preparations were analyzed
      simultaneously with and under the same conditions as the corpus cavernosum. The
      results are as follows: The concentrations of ATP and CP in the corpora were
      significantly lower than the concentrations in bladder. In the corpora, the
      tissue concentration of CP was lower than the tissue concentration of ATP,
      whereas the concentration of CP in the bladder was higher than the concentration
      of ATP. The rate of glucose metabolism to lactic acid and to carbon dioxide was
      similar for both bladder smooth muscle and corpus cavernosum. The maximal
      enzymatic activity of the mitochondrial enzyme citrate synthase was similar for
      both tissues; similarly, there was no significant difference in the activity of
      malate dehydrogenase between the two tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288488
TI  - Platelet-activating factor acetylhydrolase activity in bovine seminal plasma.
AB  - Platelet-activating factor (PAF) is a potent signaling molecule that has been
      detected in mammalian sperm from several species. The biological function of
      sperm-derived PAF and mechanisms controlling its production have not been clearly
      defined. In the remodeling pathway for PAF biosynthesis, PAF is produced by
      phospholipase A2 hydrolysis of 1-O-alkyl phospholipids followed by acetylation by
      PAF acetyltransferase. PAF is inactivated by PAF acetylhydrolase. PAF
      acetylhydrolase activity has been detected recently in human seminal plasma,
      where it may play a role in regulating PAF production or content by sperm. The
      purpose of this study was to measure and partially characterize PAF
      acetylhydrolase in bovine seminal plasma. Acetylhydrolase activity was detected
      in seminal plasma, was linear with time and protein concentration, and had a
      specific activity of 122 nmol/minute/mg protein. The enzyme was cation
      independent and was not inhibited by phosphatidylcholine but was inhibited by p
      bromophenacylbromide and partially inhibited by phenylmethylsulfonylfluoride.
      Very little acetylhydrolase activity was detected in caudal epididymal fluid or
      caudal epididymal sperm. Enzyme activity associated with ejaculated sperm was
      largely removed by their centrifugation through Percoll and subsequent washing.
      These results demonstrate very high PAF acetylhydrolase activity in bovine
      seminal plasma. The enzyme appears to be of accessory gland origin and has
      properties similar to those of the enzyme from other sources.

PMID- 8288489
TI  - Appearance of alpha-smooth muscle actin in peritubular cells of monkey testes is
      induced by androgens, modulated by follicle-stimulating hormone, and maintained
      after hormonal withdrawal.
AB  - This study analyzed the hormonal requirements necessary for the development of
      primate testicular peritubular cells. Alpha-smooth muscle actin, as a specific
      differentiation marker for peritubular cells, was immunohistochemically detected
      in the testes of immature rhesus and adult rhesus and cynomolgus monkeys.
      Positive staining was localized in the wall of blood vessels and in peritubular
      myoid cells of adult animals. In the testis of vehicle-treated immature monkeys
      no positive staining could be detected in peritubular cells. Following follicle
      stimulating hormone (FSH) or testosterone treatment, immunostaining for alpha
      smooth muscle actin appeared in peritubular cells of immature animals. In
      comparison to FSH, testosterone was more effective in inducing the
      differentiation of peritubular cells. The most intense label for alpha-smooth
      muscle actin was, however, obtained after combined treatment with FSH and
      testosterone. A computer-assisted image analysis system was used to evaluate
      semiquantitative data for the alpha-smooth muscle actin positive area; this
      confirmed a significantly higher expression of alpha-smooth muscle actin in
      peritubular cells of immature monkeys after treatment with testosterone plus FSH
      in comparison to controls. These data present evidence that the differentiation
      of primate peritubular cells during pubertal sexual development is a hormone
      dependent process, which may be predominantly regulated by androgens. FSH exerted
      additive effects on the androgen-induced differentiation of peritubular cells,
      suggesting that paracrine communication between peritubular cells and Sertoli
      cells existed. Maintenance of peritubular cell differentiation after withdrawal
      of hormonal stimuli in adult monkeys may be a possible explanation for different
      hormonal requirements during reinitiation of spermatogenesis after testicular
      involution.

PMID- 8288490
TI  - Endocrinological, biophysical, and biochemical parameters of semen collected via
      masturbation versus sexual intercourse.
AB  - In clinical programs of assisted reproduction involving infertile males, it is
      essential to obtain semen of maximum quality. To evaluate ways of achieving this
      objective, and to assess the fertilizing capacity of the sperm, six semen samples
      were collected from each of 38 infertile men via masturbation. Six more samples
      were then collected from each man at sexual intercourse using a semen collection
      device (SCD). We confirmed that the volume of seminal plasma, total sperm count,
      sperm motility, and percentage of morphologically normal spermatozoa were
      significantly higher in samples collected at intercourse than masturbation, as
      reported previously. In addition, the markers of the secretory function of the
      prostate and the outcome of sperm function tests (hypoosmotic swelling test,
      acrosin assay, and sperm penetration assay) were significantly higher for the
      samples collected at intercourse. There were no significant differences in
      markers of the secretory function of the seminal vesicles and epididymis between
      the samples. The improved spermatozoal parameters in the samples collected at
      intercourse may reflect a higher prostatic secretory function at that time. There
      were no significant differences in the serum concentrations of gonadotropins, or
      in the serum or seminal plasma concentrations of testosterone, before or after
      masturbation or sexual intercourse. Therefore, the differences in prostatic
      secretory function and semen parameters may not be attributed to differences in
      hormonal levels. Semen collection during intercourse using an SCD appears to be
      the method of choice for selecting semen samples for artificial insemination.

PMID- 8288491
TI  - Comparison of motility and flow cytometric assessments of seminal quality in
      fresh, 24-hour extended and cryopreserved human spermatozoa.
AB  - Functional differences among fresh 24-hour extended and cryopreserved human
      spermatozoa were assessed using both computer-assisted semen analysis (CASA) and
      flow cytometry. The objective was to determine if there were interrelationships
      among various qualitative parameters of the fresh and treated samples when
      assessed by these two automated methods. Fertile donor specimens (n = 15) were
      split and examined for sperm motility and curvilinear velocity using CASA within
      1 hour postejaculation, after 24 hours in TEST-yolk buffer at 5 degrees C and
      after cryopreservation in TEST-yolk-glycerol medium. Flow cytometric analyses
      were performed on 24-hour extended and cryopreserved (CP) samples after
      fluorescent staining with rhodamine 123 to quantify mitochondrial function and
      carboxydimethyl fluorescein diacetate and propidium iodide to assess plasma
      membrane integrity. The percentages of spermatozoa with functional mitochondria
      and intact membranes along with the proportion of dead cells were identified and
      quantified by flow cytometry. Quadrant analyses of these data were used to
      determine the relative red and green fluorescent intensities. The initial sperm
      motility was correlated to the motility observed for the 24-hour stored and the
      CP samples. The sperm velocity of both the initial and the 24-hour extended
      samples was correlated to the velocity of CP samples. As for the comparison of
      the two automated methods for assessing seminal quality, the only sperm motion
      parameter that was correlated with a sperm population identified by flow
      cytometry (quadrant 4) was the curvilinear velocity of the sperm after 24 hours
      storage (r = 0.69) and after cryopreservation (r = 0.74). The present findings
      indicate that additional research is needed to determine if prefreeze analyses of
      donor sperm could be useful in predicting the post-thaw integrity of CP samples
      and, thereby, be useful in screening potential semen donors.

PMID- 8288493
TI  - The prevention of invasive aspergillosis--a realistic goal?

PMID- 8288492
TI  - Operational standards for CASA instruments.
AB  - Computer-aided sperm analysis (CASA) technology is 7 years old. Over 120 papers
      have been written that verify the technology or apply it in basic and clinical
      studies. Most of the technical problems with CASA, such as the dependence of
      velocity on video frame rate, inaccuracy of count and percent motility for low-
      and high-concentration specimens, parameter dependence on the number of frames
      analyzed, sensitivity of the subjective threshold setting, confusion over the
      presence of debris, and different implementations of algorithms across
      instruments, still persist. A critical review of the literature reveals that no
      standard practices are followed within or across instruments. Moreover, no
      standards have been embraced or recommended by professional societies. Despite
      its potential to provide objective measurements of specimen and individual sperm
      parameters, and to automate the laboratory semen analysis, the promise of CASA
      has not been fulfilled. Unless laboratory medicine defines instrument performance
      and laboratory standards and co-operates with industry to achieve these goals,
      CASA technology may remain a research curiosity. This outcome is especially
      worrisome in the context of increasing requirements for laboratory accuracy,
      precision, standardization, and accreditation under the Clinical Laboratory
      Improvement Act of 1988.

PMID- 8288494
TI  - The post-antibiotic effect.
AB  - Pharmacodynamics are being applied increasingly to the design of antibiotic
      dosing regimens. One characteristic of pharmacodynamics is the post-antibiotic
      effect (PAE), the delayed regrowth of bacteria following exposure to an
      antibiotic. In this review the various laboratory techniques which have been used
      to determine the PAE are critically evaluated and compared with the standard
      viable counting method. The potential sources of error associated with these
      methods are considered and recommendations are made for the optimum testing
      system; on the basis of current evidence the bioluminescence and impedence
      techniques appear to be the most suitable in terms of being the least labour
      intensive and producing the most reliable results. Whichever technique is used,
      the properties of the growth medium, including osmolality and pH, the size of the
      bacterial inoculum, the initial antibiotic concentration, the exposure time to
      the antibiotic and the method of antibiotic removal should be standardized. Other
      post-(antibiotic) exposure events and their relationships with the PAE and
      theories concerning the mechanism (or mechanisms) by which antibiotics produce
      PAEs are discussed. Finally, consideration is given to the clinical significance
      of the PAE and how it, in conjunction with other pharmacodynamic parameters,
      might be used to allow antibiotic dosing regimens to be developed on a more
      scientific basis.

PMID- 8288495
TI  - A study on the mechanism of action of sceptrin, an antimicrobial agent isolated
      from the South Pacific sponge Agelas mauritiana.
AB  - The mechanism of action of sceptrin, an antimicrobial agent isolated from the
      sponge Agelas mauritiana, was investigated. Sceptrin has been reported to exhibit
      antibacterial and antifungal activities. In our studies, sceptrin demonstrated a
      bacteriostatic rather than bactericidal effect on exponentially growing
      Escherichia coli cells at the MIC. Under these conditions, the culture produced
      chains of cells, and incorporation of radio-labelled precursors into DNA,
      protein, and cell wall was unaffected, whereas incorporation of 3H-uridine into
      RNA was slightly inhibited. At concentrations higher than the MIC, sceptrin was
      bactericidal, inhibited the incorporation of all radiolabelled precursors, and
      induced the formation of unusual spheroplasts. Peptidoglycan turnover in E. coli
      appeared to be stimulated by sceptrin as demonstrated by a release of
      diaminopimelic acid-containing high molecular weight material. Subsequent studies
      of the release of potassium ions from E. coli and the lysis of red blood cells
      suggested that sceptrin disrupts the cell membranes of both prokaryotic and
      eukaryotic cells. It is proposed that spheroplasts formation may reflect a cell
      wall effect that occurs subsequent to membrane damage.

PMID- 8288496
TI  - Vancomycin binding to cell walls of non-streptococcal vancomycin-resistant
      bacteria.
AB  - The availability of peptidoglycan for binding to vancomycin was investigated in
      intrinsically vancomycin-resistant clinical isolates of Leuconostoc
      mesenteroides, Lactobacillus viridescens and Pediococcus pentosaceus. Intrinsic
      vancomycin resistance expressed by L. mesenteroides and P. pentosaceus was the
      result of poor binding of vancomycin to native or SDS-treated cell walls. Pre
      exposure of L. viridescens to vancomycin decreased the subsequent binding of
      vancomycin to the cell walls, suggesting an alternative mechanism to that found
      in high-level vancomycin-resistant enterococci and intrinsically-resistant L.
      mesenteroides and P. pentosaceus. Vancomycin binding was sensitive to
      substitution of larger side chains at the C-terminus. Variations of peptidoglycan
      peptide types found in L. mesenteroides, L. viridescens and P. pentosaceus could
      account for their intrinsic vancomycin resistance.

PMID- 8288497
TI  - Extended-spectrum beta-lactamases in Escherichia coli and Klebsiella spp. in
      European septicaemia isolates.
AB  - Five per cent of Escherichia coli and klebsiella septicaemia isolates from the
      European Study Group on Antibiotic Resistance (ESGAR) study in 1987 to 1988
      showed reduced susceptibility or resistance to cefotaxime, ceftazidime
      and/oraztreonam. Six of 15 isolates studied were susceptible to cefoxitin and
      MICs of cefuroxime, cefotaxime, ceftazidime and aztreonam were reduced by
      clavulanic acid. The isoelectric points of their beta-lactamases were in the
      range of 5.3-7.6. DNA hybridization showed that four of these beta-lactamases
      belonged to the TEM or SHV family. Transfer of cefotaxime resistance by
      conjugation was seen in two of the strains. Nine strains were resistant to
      cefoxitin (MIC > 16 mg/L) and MICs of cefuroxime, cefotaxime, ceftazidime and
      aztreonam were only slightly reduced in the presence of clavulanic acid. All nine
      strains produced at least one beta-lactamase of chromosomal origin with pI > 8.4,
      and four of these strains also harboured beta-lactamases with a pI range of 6.6
      8.2. Cefoxitin resistance could be transferred by conjugation in one strain. Thus
      E. coli and Klebsiella spp. from the ESGAR septicaemia isolates were found to
      produce extended-spectrum beta-lactamases of both chromosomal and plasmid origin.

PMID- 8288498
TI  - Microbroth versus agar dilution for susceptibility testing of fluoroquinolones
      and other agents against anaerobic bacteria.
AB  - Agar dilution and microbroth dilution methods appear equally acceptable for
      susceptibility testing of anaerobes against temafloxacin and ciprofloxacin. Most
      major discrepancies occurred with strains whose MIC was near the breakpoint.
      These results suggest that method variation will not be a significant factor in
      the susceptibility testing of anaerobic bacteria against other fluoroquinolone
      agents.

PMID- 8288499
TI  - The bactericidal activity of magainins against Pseudomonas aeruginosa and
      Enterococcus faecium.
AB  - The antimicrobial activities of two synthetic magainins, MSI 94 and MSI 93, were
      investigated in vitro against 20 clinical isolates each of Pseudomonas aeruginosa
      and Enterococcus faecium. The ranges of the MICs of both agents were 6.25-50 mg/L
      for P. aeruginosa and 3.13-12.5 mg/L for E. faecium. In time-kill studies, the
      magainins demonstrated rapid, concentration-dependent bactericidal activity
      against selected isolates of both species. This bactericidal effect was inoculum
      dependent for P. aeruginosa in both the logarithmic and stationary phases of
      growth. Bacterial regrowth was regularly observed after 24 h of incubation in the
      time-kill studies; this was due to loss of antimicrobial activity during
      overnight incubation rather than to the development of resistance. More rapid and
      sustained bactericidal activity was noted when the magainins were combined with
      either silver nitrate (AgNO3) or gentamicin against P. aeruginosa and with
      gentamicin against E. faecium. Neither agent produced a post-antibiotic effect on
      P. aeruginosa.

PMID- 8288500
TI  - Antimicrobial susceptibility of Rochalimaea quintana, Rochalimaea vinsonii, and
      the newly recognized Rochalimaea henselae.
AB  - The susceptibility of an isolate of Rochalimaea quintana, Rochalimaea vinsonii
      and the newly recognized Rochalimaea henselae to antimicrobial agents was
      determined by dilution in Mueller-Hinton agar supplemented with 5% sheep blood.
      Two inocula of 10(2) and 10(4) cfu were used and tests were read after incubation
      at 5 and 7 days at 37 degrees C in an atmosphere enriched to 5% carbon dioxide.
      Each isolate was susceptible to amoxycillin, third-generation cephalosporins,
      tetracyclines, macrolides and rifampicin, with complete inhibition of bacterial
      growth at concentrations lower than 0.125 mg/L. Co-trimoxazole and
      aminoglycosides were also active. Conversely, MICs for oxacillin, cephalothin,
      clindamycin, chloramphenicol and the fluoroquinolones were around the maximum
      concentrations achievable in serum. Vanocomycin showed moderate activity with
      MICs of < or = 4 mg/L. These results are consistent with clinical experience in
      antibiotic treatment of R. henselae infections since failures were reported with
      first-generation cephalosporins and the isoxazolyl penicillins. However, the
      frequent relapses that are observed with other beta-lactams, tetracyclines or
      macrolides do not accord with the in-vitro susceptibility of Rochalimaea spp.
      Poor bactericidal activity as well as the intracellular growth of the bacteria
      within infected hosts, may explain such discrepancies.

PMID- 8288501
TI  - Characterization of ceftriaxone-resistant Enterobacteriaceae: a multicentre study
      in 26 French hospitals. Vigil'Roc Study Group.
AB  - During a multicentre study performed in 26 French hospitals, 287 (3.2%) of 9038
      Enterobacteriaceae isolated, mainly Enterobacter spp., Serratia spp., Citrobacter
      spp. and Klebsiella spp. were classified as ceftriaxone resistant on the basis of
      an MIC > 4 mg/L or the presence of an extended-spectrum beta-lactamase. Extended
      spectrum beta-lactamase was present mainly in Klebsiella pneumoniae (65 strains,
      10.2%) and very rarely in Escherichia coli, Proteus mirabilis, Klebsiella
      oxytoca, Citrobacter spp. and Enterobacter spp. The extended-spectrum beta
      lactamases conferred low-level resistance to ceftriaxone in nearly 60% of the
      strains harbouring them, emphasizing the need for routine testing for the
      presence of these enzymes. Among transconjugants three types of extended-spectrum
      beta-lactamase were identified. Those resembling TEM-3 were the most common, but
      TEM-21, and SHV-4 were also found. Clavulanate and to a lesser extent sulbactam
      inhibited all the extended-spectrum beta-lactamases encountered in this study.

PMID- 8288502
TI  - High-level quinolone resistance amongst clinical isolates of Escherichia coli and
      Klebsiella pneumoniae from Spain.
AB  - A recombinant plasmid containing gyr A encoding wild-type Escherichia coli
      quinolone susceptible DNA gyrase A subunits has been used as a broad host range
      gene probe. Strains expressing gyr A-mediated quinolone resistance become
      susceptible to quinolones upon insertion of the plasmid, whereas the plasmid
      without gyrA (pLA2917, vector) has no effect. Fifteen highly ciprofloxacin
      resistant E. coli and three Klebsiella pneumoniae (MICs 2-64 mg/L) were isolated
      from clinical specimens in the Hospital de la Princesa, Madrid, Spain. Plasmid
      pNJR3-2 and pLA2917 were introduced into the clinical isolates by conjugation,
      and transconjugants selected with tetracycline or kanamycin (for which the
      plasmids encode resistance). Ten transconjugants from each mating, the original
      isolates, the gene probe and vector control were screened for susceptibility to
      nalidixic acid, ciprofloxacin, ofloxacin, norfloxacin, tetracycline,
      chloramphenicol, cefoxitin and trimethoprim. Lower MICs of quinolones were seen
      for the transconjugants of two K. pneumoniae isolates in the presence of the gene
      probe, suggesting that these isolates harboured mutations in gyr A. Plasmid
      profiles confirmed the presence of the probe. The susceptibility of the third K.
      pneumoniae strain and all E. coli isolates were unaffected by insertion of the
      plasmid, suggesting another mechanism was responsible for quinolone resistance.

PMID- 8288503
TI  - The optimal dosage of ceftazidime for severe lower respiratory tract infections.
AB  - The optimal dosage of antibiotics for the treatment of patients with severe lower
      respiratory tract infections (LRTI) has not been determined but may be lower than
      is commonly administered at present. We have compared the efficacy of a low
      dosage of ceftazidime (1 g tds) with the more usual dosage (2 g tds) in a
      prospective, randomized study of the treatment of LRTI in seriously ill patients.
      Fifty patients on an Intensive Care Unit received one or the other regimen for 5
      days; the demographic characteristics of the two groups were comparable. There
      was no significant difference in terms of clinical and microbiological response
      rates between the two regimens. Overall, clinical resolution was documented for
      86% of patients, there was no change in 8% and 6% deteriorated. Microbiological
      eradication was achieved in 52% of patients from whom a pathogen was isolated
      (46% of all patients). We conclude that ceftazidime 1 g tds is effective
      treatment for severe LRTI in hospitalized patients.

PMID- 8288504
TI  - Inhibition of Mycobacterium avium complex isolates from AIDS patients by garlic
      (Allium sativum).

PMID- 8288505
TI  - Clarithromycin lacks bactericidal activity in cerebrospinal fluid in experimental
      pneumococcal meningitis.

PMID- 8288506
TI  - Antibiotic usage in an intensive care unit in a Danish university hospital.
AB  - We report a study of antimicrobial use in patients admitted to the Intensive Care
      Unit (ICU) in a Danish university hospital during the course of 1 year. Of 615
      patients admitted, 434 (71%) received antibiotics, 220 (36%) for infections and
      222 (36%) for prophylaxis. Therapy for suspected infection accounted for 67% of
      the total consumption of antibiotics and prophylaxis for 33%. Ampicillin was the
      drug most frequently used; 43% of the patients treated for infection received
      this drug. One hundred and thirty-one patients (60%) were treated for suspected
      lower respiratory tract infection. Relevant microbiological specimens were
      obtained from 120 (92%) of these patients and a possible pathogen was isolated in
      92 patients (77%, 92/120). Staphylococcus aureus and Streptococcus pneumoniae
      were each isolated in almost a quarter of the patients, and Enterobacteriaceae in
      53%. However, many of the pathogens isolated were of no clinical relevance and
      merely reflected a state of colonization. Most treatments were given during the
      first few days following admission. Of 220 patients receiving antibiotics for an
      infection, 87% were treated on day 1, but only 34% (14 of 41) on day 11. The
      frequent use of laboratory investigations combined with good communication
      between clinicians and microbiologists probably resulted in rapid cessation of
      unnecessary therapy. Fifty-two per cent of the antibiotics given for prophylaxis
      were administered later than the first postoperative day. This study emphasizes
      the need for consultation between surgeons and clinical microbiologists to
      supervise postoperative antibiotic use.

PMID- 8288507
TI  - Variable patient compliance in ambulatory trials--nuisance, threat, opportunity.

PMID- 8288508
TI  - Effects of beta-lactamase inducibility and derepression on the activity of
      cefpirome against gram-negative bacteria.

PMID- 8288509
TI  - Roxithromycin in-vitro susceptibility testing of Haemophilus influenzae by NCCLS
      methods. National Committee for Clinical Laboratory Standards.

PMID- 8288510
TI  - Antimicrobial activity of FK-037 against class I beta-lactamase producing species
      resistant to ceftazidime: a multi-laboratory clinical isolate sample.

PMID- 8288511
TI  - Cefodizime enhances formyl-methionyl-leucyl-phenylalanine-induced hydrogen
      peroxide production from human neutrophils.

PMID- 8288512
TI  - Efficacy of liposomal amphotericin B in the treatment and secondary prophylaxis
      of visceral leishmaniasis in HIV infected patients: report of two cases.

PMID- 8288513
TI  - An application of electronic imaging technology in biotechnology research.

PMID- 8288514
TI  - "The Informer": a remote emergency notification device.

PMID- 8288515
TI  - The invisible image--a tutorial on photography with invisible radiation, Part 1:
      Introduction and reflected ultraviolet techniques.

PMID- 8288516
TI  - An interview with C. Graham Eddy, RBP, FBPA. Interview by Marilee A. Caliendo.

PMID- 8288517
TI  - The distinction of eosinophils from other hematopoietic cells by darkfield
      illumination.

PMID- 8288518
TI  - Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive
      transcriptional regulators.

PMID- 8288519
TI  - Isolation and characterization of Bacillus subtilis genomic lacZ fusions induced
      during partial purine starvation.
AB  - Random genomic Bacillus subtilis lacZ fusions were screened in order to identify
      the possible existence of regulons responding to the stimuli generated by partial
      purine starvation. A leaky pur mutation (purL8) was isolated and used to generate
      the partial purine starvation conditions in the host strain used for screening.
      On the basis of their induction during partial purine starvation, seven genomic
      lacZ fusions were isolated. None of the fusions map in loci previously reported
      to contain purine-regulated genes. One fusion maps very close to the citB locus
      and may very well be a citB fusion. The fusions were divided into two types on
      the basis of their response to complete starvation for either ATP or GTP or both
      components at the same time. Except for one, type 2 fusions were induced by
      specific starvation for ATP and by simultaneous starvation for ATP and GTP, but
      not by specific GTP starvation in a gua strain or by GTP starvation induced by
      the addition of decoyinine. Type 1 fusions were equally well induced by all three
      kinds of purine starvation including GTP starvation induced by decoyinine.
      Further subdivisions of the fusions were obtained on the basis of their responses
      to the spo0A gene product. A total of five fusions showed that spo0A affected
      expression. One class was unable to induce lacZ expression in the absence of the
      spo0A gene product, whereas the other class had increased lacZ expression during
      partial purine starvation in a spo0A background.

PMID- 8288520
TI  - The cell envelope structure of the lipopolysaccharide-lacking gram-negative
      bacterium Sphingomonas paucimobilis.
AB  - From the cell envelope preparation of Sphingomonas paucimobilis two membrane
      fractions with different densities were separated by sucrose density gradient
      ultracentrifugation. The high-density fraction contained several major proteins,
      phospholipids, and glycosphingolipids, which are the only glycolipids of this
      lipopolysaccharide-lacking gram-negative bacterium. The low-density fraction
      showed many minor bands of proteins by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and NADH oxidase activity was localized in this fraction.
      Combined with morphological data of vesicles formed by these membrane fractions,
      the high-density and low-density fractions were proposed to be an outer membrane
      and a cytoplasmic membrane, respectively. The localization of the
      glycosphingolipid was investigated also by means of immunoelectron microscopic
      analysis using a glycosphingolipid-specific antibody. The glycosphingolipid was
      shown to localize at the cell envelope, and the antigenic sugar portion was
      exposed to the bacterial cell surface. From these results the glycosphingolipid
      was assumed to have a function similar to that of the lipopolysaccharide of other
      gram-negative bacteria.

PMID- 8288521
TI  - In vivo and in vitro nickel-dependent processing of the [NiFe] hydrogenase in
      Azotobacter vinelandii.
AB  - H2 oxidation in Azotobacter vinelandii is catalyzed by a membrane-bound, alpha
      beta dimeric [NiFe] hydrogenase. Maturation of the enzyme involves cleavage of a
      putative N-terminal signal sequence in the beta subunit and removal of 15 amino
      acids from the C terminus of the alpha subunit. Cells limited for nickel
      exhibited low hydrogenase activities and contained an apparently large form of
      the alpha subunit. Addition of nickel to such cells increased hydrogenase
      activities fivefold over 2 h. The increase in the first hour did not require
      transcription and translation and correlated with processing of the large form of
      the alpha subunit (pre-alpha) to the small form (alpha) resembling the alpha
      subunit from the purified enzyme. In vivo, pre-alpha appeared soluble whereas the
      majority of alpha was membrane bound. Processing of pre-alpha to alpha was
      reproduced in vitro in membrane-depleted extracts of nickel-limited cells.
      Processing specifically required the addition of Ni2+, whereas Co2+, Cu2+, Ca2+,
      Fe2+, Mn2+, and Zn2+ were ineffective. However, Zn2+, Co2+, and Cu2+ inhibited
      nickel-dependent processing. Mg-ATP and Mg-GTP stimulated processing, whereas
      anaerobic conditions and/or the addition of dithiothreitol and sodium dithionite
      was unnecessary. Processing was not inhibited by the protease inhibitors
      phenylmethylsulfonyl fluoride, E64, and pepstatin.

PMID- 8288522
TI  - Phosphorylation of Bacillus subtilis transcription factor Spo0A stimulates
      transcription from the spoIIG promoter by enhancing binding to weak 0A boxes.
AB  - Activation of the spoIIG promoter at the onset of sporulation in Bacillus
      subtilis requires the regulatory protein, Spo0A, which binds to two sites in the
      promoter, sites 1 and 2. Phosphorylation of Spo0A is essential for the initiation
      of sporulation. Therefore, we examined the role of Spo0A phosphorylation in
      spoIIG promoter activation. Phosphorylation of Spo0A stimulated transcription
      from the spoIIG promoter in vitro. In DNAse I footprinting experiments with the
      spoIIG promoter, we found that phosphorylation of Spo0A increased its affinity
      for site 2 more than for site 1, which is the site to which nonphosphorylated
      Spo0A binds most avidly. This result could not be explained by increased
      cooperativity between Spo0A bound at sites 1 and 2 because the increased affinity
      for site 2 by phosphorylated Spo0A was also observed with a deletion derivative
      of the spoIIG promoter containing only site 2. We have located Spo0A-binding
      sequences in the spoIIG promoter by DMS protection assays and mutational
      analysis, and found that site 1 contains one higher-affinity binding sequence
      whereas site 2 contains two weaker-binding sites. Two substitutions in site 2 of
      the spoIIG promoter that change the sequence to be more like an optimal Spo0A
      binding site were found to increase promoter activity. Moreover, phosphorylation
      of Spo0A was not required in vivo for activation of the spoIIG promoter
      containing these strong binding sites. The results suggest that the primary role
      for phosphorylation of Spo0A is to increase its affinity for specific sites
      rather than to activate an activity of Spo0A that acts on RNA polymerase at
      promoters.

PMID- 8288523
TI  - FptA, the Fe(III)-pyochelin receptor of Pseudomonas aeruginosa: a phenolate
      siderophore receptor homologous to hydroxamate siderophore receptors.
AB  - The Pseudomonas aeruginosa siderophore pyochelin is structurally unique among
      siderophores and possesses neither hydroxamate- nor catecholate-chelating groups.
      The structural gene encoding the 75-kDa outer membrane Fe(III)-pyochelin receptor
      FptA has been isolated by plasmid rescue techniques and sequenced. The N-terminal
      amino acid sequence of the isolated FptA protein corresponded to that deduced
      from the nucleotide sequence of the fptA structural gene. The mature FptA protein
      has 682 amino acids and a molecular mass of 75,993 Da and has considerable
      overall homology with the hydroxamate siderophore receptors FpvA of P.
      aeruginosa, PupA and PupB of Pseudomonas putida, and FhuE of Escherichia coli.
      This observation indicates that homologies between siderophore receptors are an
      unreliable predictor of siderophore ligand class recognition by a given receptor.
      The fptA gene was strongly regulated by iron; fptA transcription was totally
      repressed by 30 microM FeCl3, as determined by Northern (RNA) blotting. The
      promoter of the fptA gene contained the sequence 5'-ATAATGATAAGCATTATC-3', which
      matches the consensus E. coli Fur-binding site at 17 of 18 positions. The -10
      promoter region and transcriptional start site of the fptA gene reside within
      this Fur-binding site.

PMID- 8288524
TI  - In vitro characterization of a phosphate starvation-independent carbon-phosphorus
      bond cleavage activity in Pseudomonas fluorescens 23F.
AB  - A novel, metal-dependent, carbon-phosphorus bond cleavage activity, provisionally
      named phosphonoacetate hydrolase, was detected in crude extracts of Pseudomonas
      fluorescens 23F, an environmental isolate able to utilize phosphonoacetate as the
      sole carbon and phosphorus source. The activity showed unique specificity toward
      this substrate; its organic product, acetate, was apparently metabolized by the
      glyoxylate cycle enzymes of the host cell. Unlike phosphonatase, which was also
      detected in crude extracts of P. fluorescens 23F, phosphonoacetate hydrolase was
      inducible only in the presence of its sole substrate and did not require
      phosphate starvation.

PMID- 8288525
TI  - Pathway of glycogen metabolism in Methanococcus maripaludis.
AB  - Methanococcus maripaludis, a facultatively autotrophic archaebacterium that grows
      with H2 or formate as the electron donor, does not assimilate sugars and other
      complex organic substrates. However, glycogen is biosynthesized intracellularly
      and commonly reaches values of 0.34% of the cellular dry weight in the early
      stationary phase. To determine the pathway of glycogen catabolism, specific
      enzymes of sugar metabolism were assayed in cell extracts. The following enzymes
      were found (specific activity in milliunits per milligram of protein): glycogen
      phosphorylase, 4.4; phosphoglucomutase, 10; glucose-6-phosphate isomerase, 9; 6
      phosphofructokinase, 5.6, fructose-1,6-bisphosphatase, 10; fructose-1,6
      bisphosphate aldolase, 4.2; triosephosphate isomerase, 44; glyceraldehyde-3
      phosphate dehydrogenase, 26; phosphoglycerate kinase, 20; phosphoglycerate
      mutase, 78; enolase, 107; and pyruvate kinase, 4.0. Glyceraldehyde-3-phosphate
      dehydrogenase was NADP+ dependent, and the pyruvate kinase required MnCl2. The 6
      phosphofructokinase had an unusually low pH optimum of 6.0. Four nonoxidative
      pentose-biosynthetic enzymes were found (specific activity in milliunits per
      milligram of protein): transketolase, 12; transaldolase, 24; ribulose-5-phosphate
      3-epimerase, 55; and ribulose-5-phosphate isomerase, 100. However, the key
      enzymes of the oxidative pentose phosphate pathway, the reductive pentose
      phosphate pathway, and the classical and modified Entner-Duodoroff pathways were
      not detected. Thus, glycogen appears to be catabolized by the Embden-Meyerhoff
      Parnas pathway. This result is in striking contrast to the nonmethanogenic
      archaebacteria that have been examined, among which the Entner-Doudoroff pathway
      is common. A dithiothreitol-specific NADP(+)-reducing activity was also found
      (8.5 mU/mg of protein). Other thiol compounds, such as cysteine hydrochloride,
      reduced glutathione, and 2-mercaptoethanesulfonic acid, did not replace
      dithiothreitol for this activity. The physiological significance of this activity
      is not known.

PMID- 8288526
TI  - Interspecies recombination between the penA genes of Neisseria meningitidis and
      commensal Neisseria species during the emergence of penicillin resistance in N.
      meningitidis: natural events and laboratory simulation.
AB  - The penicillin-binding protein 2 genes (penA) of penicillin-resistant Neisseria
      meningitidis have a mosaic structure that has arisen by the introduction of
      regions from the penA genes of Neisseria flavescens or Neisseria cinerea.
      Chromosomal DNA from both N. cinerea and N. flavescens could transform a
      penicillin-susceptible isolate of N. meningitidis to increased resistance to
      penicillin. With N. flavescens DNA, transformation to resistance was accompanied
      by the introduction of the N. flavescens penA gene, providing a laboratory
      demonstration of the interspecies recombinational events that we believe underlie
      the development of penicillin resistance in many meningococci in nature.
      Surprisingly, with N. cinerea DNA, the penicillin-resistant transformants did not
      obtain the N. cinerea penA gene. However, the region of the penA gene derived
      from N. cinerea in N. meningitidis K196 contained an extra codon (Asp-345A) which
      was not found in any of the four N. cinerea isolates that we examined and which
      is known to result in a decrease in the affinity of PBP 2 in gonococci.

PMID- 8288527
TI  - Purification and properties of a membrane-bound lytic transglycosylase from
      Escherichia coli.
AB  - A membrane-bound lytic transglycosylase (Mlt) has been solubilized in the
      presence of 2% Triton X-100 containing 0.5 M NaCl from membranes of an
      Escherichia coli mutant that carries a deletion in the slt gene coding for a 70
      kDa soluble lytic transglycosylase (Slt70). The enzyme was purified by a four
      step procedure including anion-exchange (HiLoad SP-Sepharose and MonoS), heparin
      Sepharose, and poly(U)-Sepharose 4B column chromatography. The purified protein
      that migrated during denaturing sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis as a single band corresponding to an apparent molecular mass of
      about 38 kDa is referred to as Mlt38. Optimal activity was found in buffers with
      a pH between 4.0 and 4.5. The enzyme is stimulated by a factor of 2.5 in the
      presence of Mg2+ at a concentration of 10 mM and loses its activity rapidly at
      temperatures above 30 degrees C. Besides insoluble murein sacculi, the enzyme was
      able to degrade glycan strands isolated from murein by amidase treatment. The
      enzymatic reaction occurred with a maximal velocity of about 2.2 mg/liter/min
      with murein sacculi as a substrate. The amino acid sequences of four proteolytic
      peptides showed no identity with known sequences in the data bank. With Mlt38,
      the number of proteins in E. coli showing lytic transglycosylase activity rises
      to three.

PMID- 8288528
TI  - DcrA, a c-type heme-containing methyl-accepting protein from Desulfovibrio
      vulgaris Hildenborough, senses the oxygen concentration or redox potential of the
      environment.
AB  - The amino acid sequence of DcrA from Desulfovibrio vulgaris Hildenborough, a
      strictly anaerobic, sulfate-reducing bacterium, indicated homology with the
      methyl-accepting chemotaxis proteins from enteric bacteria (A. Dolla, R. Fu, M.
      J. Brumlik, and G. Voordouw, J. Bacteriol. 174:1726-1733, 1992). The homology is
      restricted to the cytoplasmic C-terminal signaling domain. The periplasmic N
      terminal sensor domain was found to contain a unique sequence, CHHCH,
      corresponding to a consensus c-type heme binding site. A pretreated, DcrA
      specific polyclonal antiserum, generated against DcrA protein overproduced in
      Escherichia coli, was used for immunoprecipitation of 35S-labeled DcrA from D.
      vulgaris and Desulfovibrio desulfuricans G200(pJRFR2), a transconjugant that
      overexpresses functional DcrA. Labeling of the latter with the heme precursor 5
      amino-[4-14C]levulinic acid, followed by immunoprecipitation, sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, and fluorography, confirmed the
      presence of c-type heme, while labeling with L-[methyl-3H]methionine in the
      absence of protein synthesis confirmed that DcrA is a methyl-accepting protein.
      The base liability of the incorporated radioactivity indicated methyl ester
      formation like that occurring in the methyl-accepting chemotaxis proteins of
      enteric bacteria. L-[methyl-3H]methionine labeling of D. desulfuricans
      G200(pJRFR2) under different conditions indicated that methyl labeling of DcrA
      decreased upon addition of oxygen and increased upon subsequent addition of the
      reducing agent dithionite. These results indicate that DcrA may serve as a sensor
      of oxygen concentration and/or redox potential.

PMID- 8288529
TI  - Identification of a large family of genes for putative chemoreceptor proteins in
      an ordered library of the Desulfovibrio vulgaris Hildenborough genome.
AB  - A library of 879 recombinant lambda phages, constructed for the genome of
      Desulfovibrio vulgaris Hildenborough, has been ordered by restriction
      fingerprinting. Restriction endonuclease HinfI digestion patterns were entered
      into a data base and sorted into 87 overlapping groups (contigs), with 19 clones
      remaining unattached. Eight of ten cloned genes of D. vulgaris, including dcrA,
      which encodes a transmembrane methyl-accepting protein, were assigned to contigs.
      Probing of a filter containing the lambda DNAs of the library with the labeled,
      conserved 3' end of the dcrA gene indicated hybridization to 54 clones
      distributed over multiple contigs. The presence of 11 additional dcr genes (dcrB
      to dcrL) was confirmed by direct cycled dideoxy sequencing of positive lambda
      clones. Since the ordered library provides only partial coverage of the D.
      vulgaris Hildenborough genome, we estimate that the dcr gene family has 16
      members spread throughout the genome, making it the second largest gene family
      found in prokaryotes.

PMID- 8288530
TI  - New outer membrane-associated protease of Escherichia coli K-12.
AB  - The gene for a new outer membrane-associated protease, designated OmpP, of
      Escherichia coli has been cloned and sequenced. The gene encodes a 315-residue
      precursor protein possessing a 23-residue signal sequence. Including conservative
      substitutions and omitting the signal peptides, OmpP is 87% identical to the
      outer membrane protease OmpT. OmpP possessed the same enzymatic activity as OmpT.
      Immuno-electron microscopy demonstrated the exposure of the protein at the cell
      surface. Digestion of intact cells with proteinase K removed 155 N-terminal
      residues of OmpP, while the C-terminal half remained protected. It is possible
      that much of this N-terminal part is cell surface exposed and carries the
      enzymatic activity. Synthesis of OmpP was found to be thermoregulated, as is the
      expression of ompT (i.e., there is a low rate of synthesis at low temperatures)
      and, in addition, was found to be controlled by the cyclic AMP system.

PMID- 8288531
TI  - Mutation of flgM attenuates virulence of Salmonella typhimurium, and mutation of
      fliA represses the attenuated phenotype.
AB  - Salmonella typhimurium ST39 exhibits reduced virulence in mice and decreased
      survival in mouse macrophages compared with the parent strain SL3201. Strain ST39
      is nonmotile, carries an indeterminate deletion in and near the flgB operon, and
      is defective in the mviS (mouse virulence Salmonella) locus. In flagellum
      defective strains, the flgM gene product of S. typhimurium negatively regulates
      flagellar genes by inhibiting the activity of FliA, the flagellin-specific sigma
      factor. In this study, flgM of wild-type S. typhimurium LT2 was found to
      complement the mviS defect in ST39 for virulence in mice and for enhanced
      survival in macrophages. Transduction of flgM::Tn10dCm into the parent strain
      SL3201 resulted in attenuation of mouse virulence and decreased survival in
      macrophages. However, a flgM-fliA double mutant was fully virulent in mice and
      survived in macrophages at wild-type levels. Thus, the absolute level of FliA
      activity appears to affect the virulence of S. typhimurium SL3201 in mice. DNA
      hybridization studies showed that flgM-related sequences were present in species
      other than Salmonella typhimurium and that sequences related to that of fliA were
      common among members of the family Enterobacteriaceae. Our results demonstrate
      that flgM and fliA, two genes previously shown to regulate flagellar operons, are
      also involved in the regulation of expression of virulence of S. typhimurium and
      that this system may not be unique to the genus Salmonella.

PMID- 8288532
TI  - Escherichia coli Fis and DnaA proteins bind specifically to the nrd promoter
      region and affect expression of an nrd-lac fusion.
AB  - The Escherichia coli nrd operon contains the genes encoding the two subunits of
      ribonucleoside diphosphate reductase. The regulation of the nrd operon has been
      observed to be very complex. The specific binding of two proteins to the nrd
      regulatory region and expression of mutant nrd-lac fusions that do not bind these
      proteins are described. A partially purified protein from an E. coli cell extract
      was previously shown to bind to the promoter region and to regulate transcription
      of the nrd operon (C. K. Tuggle and J. A. Fuchs, J. Bacteriol. 172:1711-1718,
      1990). We have purified this protein to homogeneity by affinity chromatography
      and identified it as the E. coli factor for inversion stimulation (Fis). Cu
      phenanthroline footprinting experiments showed that Fis binds to a site centered
      156 bp upstream of the start of nrd transcription. Mutants with deletion and site
      directed mutations that do not bind Fis at this site have two- to threefold-lower
      expression of an nrd-lac fusion. The previously reported negative regulatory
      nature of this site (C. K. Tuggle and J. A. Fuchs, J. Bacteriol. 172:1711-1718,
      1990) was found to be due to a change in polarity in the vectors used to
      construct promoter fusions. Two nine-base sequences with homology to the DnaA
      consensus binding sequence are located immediately upstream of the nrd putative 
      35 RNA polymerase binding site. Binding of DnaA to these sequences on DNA
      fragments containing the nrd promoter region was confirmed by in vitro Cu
      phenanthroline footprinting. Footprinting experiments on fragments with each as
      well as both of the mutated 9-mers suggests cooperativity between the two sites
      in binding DnaA. Assay of in vivo expression from wild-type and DnaA box-mutated
      nrd promoter fragments fused to lacZ on single-copy plasmids indicates a positive
      effect of DnaA binding on expression of nrd.

PMID- 8288533
TI  - Rickettsial relative associated with male killing in the ladybird beetle (Adalia
      bipunctata).
AB  - A cytoplasmically inherited microorganism associated with male killing in the two
      spot ladybird beetle, Adalia bipunctata, is shown to be closely related to
      bacteria in the genus Rickettsia. Sequencing of a PCR-amplified product of the
      16S genes coding for rRNA (16S rDNA) shows the organism associated with male
      killing in ladybirds to share a common ancestry with the Rickettsias relative to
      other genera (e.g., Anaplasma, Ehrlichia, and Cowdria). The rickettsial 16S rDNA
      product is found in four strains of ladybird beetle showing male embryo lethality
      and is absent from two uninfected strains and an antibiotic-cured strain. In
      addition, a revertant strain that had naturally lost the male-killing trait
      failed to amplify the rickettsial 16S rDNA product. Use of PCR primers for a 17
      kDa protein antigen which is found only in rickettsias also resulted in an
      amplified product from infected strains. Uninfected, cured, and revertant strains
      and insect species infected with related bacteria (cytoplasmic-incompatibility
      bacteria from Nasonia wasps) failed to amplify the product. Discovery of a close
      relative of rickettsias associated with sex ratio distortion in insects has
      implications for the evolution and population dynamics of this bacterial genus.

PMID- 8288534
TI  - Analysis of surfactin synthetase subunits in srfA mutants of Bacillus subtilis
      OKB105.
AB  - The srfA operon of Bacillus subtilis functions in the biosynthesis of the
      lipopeptide antibiotic surfactin. On the basis of nucleotide sequence and genetic
      analysis, it is believed to encode three enzymes (E1A, E1B, and E2) that catalyze
      the incorporation of the surfactin substrate amino acids. Insertion, deletion,
      and amino acid substitution mutations of srfA were analyzed for subunit
      composition and activity as determined by assays of both amino acid-dependent ATP
      PPi exchange and aminoacyl thioester formation. Insertion mutations in srfAA
      (encoding E1A, the subunit that incorporates Glu, Leu, and D-Leu) eliminated
      production and activity of all three enzymes. Deletions within srfAA and
      extending from srfAA to srfAB (encoding E1B, which incorporates Val, Asp, and D
      Leu) abolished the activity and production of all three enzymes. Insertions
      between srfAA and srfAB and within srfAB eliminate the production and activity of
      E1B and E2. An insertion mutation in srfAC (encoding E2, which incorporates Leu)
      abolished the activity of E2 only. Mutations of the active serine in the putative
      4'-phosphopantetheine-binding motif of the second and third domains of E1A
      eliminated thioester formation and severely reduced the ATP-PPi exchange activity
      of the two domains. However, the same mutation in the first domain of E1B had
      little effect on Val-dependent ATP-PPi exchange activity but abolished thioester
      formation. These results indicate that the coding assignments of the srfA genes
      are srfAA (E1A), srfAB (E1B), and srfAC (E2).

PMID- 8288535
TI  - Expression of Caulobacter dnaA as a function of the cell cycle.
AB  - The initiation of DNA replication is under differential control in Caulobacter
      crescentus. Following cell division, only the chromosome in the progeny stalked
      cell is able to initiate DNA replication, while the chromosome in the progeny
      swarmer cell does not replicate until later in the cell cycle. We have isolated
      the dnaA gene in order to determine whether this essential and ubiquitous
      replication initiation protein also contributes to differential replication
      control in C. crescentus. Analysis of the cloned C. crescentus dnaA gene has
      shown that the deduced amino acid sequence can encode a 486-amino-acid protein
      that is 37% identical to the DnaA protein of Escherichia coli. The gene is
      located 2 kb from the origin of replication. Primer extension analysis revealed a
      single transcript originating from a sigma 70-type promoter. Immunoprecipitation
      of a DnaA'-beta-lactamase fusion protein showed that although expression occurs
      throughout the cell cycle, there is a doubling in the rate of expression just
      prior to the initiation of replication.

PMID- 8288536
TI  - Autogenous translational regulation of the ribosomal MvaL1 operon in the
      archaebacterium Methanococcus vannielii.
AB  - The mechanisms for regulation of ribosomal gene expression have been
      characterized in eukaryotes and eubacteria, but not yet in archaebacteria. We
      have studied the regulation of the synthesis of ribosomal proteins MvaL1, MvaL10,
      and MvaL12, encoded by the MvaL1 operon of Methanococcus vannielii, a
      methanogenic archaebacterium. MvaL1, the homolog of the regulatory protein L1
      encoded by the L11 operon of Escherichia coli, was shown to be an autoregulator
      of the MvaL1 operon. As in E. coli, regulation takes place at the level of
      translation. The target site for repression by MvaL1 was localized by site
      directed mutagenesis to a region within the coding sequence of the MvaL1 gene
      commencing about 30 bases downstream of the ATG initiation codon. The MvaL1
      binding site on the mRNA exhibits similarity in both primary sequence and
      secondary structure to the L1 regulatory target site of E. coli and to the
      putative binding site for MvaL1 on the 23S rRNA. In contrast to other regulatory
      systems, the putative MvaL1 binding site is located in a sequence of the mRNA
      which is not in direct contact with the ribosome as part of the initiation
      complex. Furthermore, the untranslated leader sequence is not involved in the
      regulation. Therefore, we suggest that a novel mechanism of translational
      feedback regulation exists in M. vannielii.

PMID- 8288537
TI  - Analysis of the replication region of a mycobacterial plasmid, pMSC262.
AB  - We determined the nucleotide sequence of a DNA fragment which contains the
      replication region of pMSC262, a Mycobacterium scrofulaceum plasmid used to
      construct the Mycobacterium-Escherichia coli shuttle vector. The complete
      sequence of the fragment contained 2,504 bp with an overall G+C content of 69.8%.
      By deletion analysis, we found that the minimum length required for plasmid
      replication in M. bovis BCG was about 1.6 kb. Within this region, several open
      reading frames (ORFs) and a putative replication origin (ori) were identified by
      computer analysis. One of the ORFs, ORF2, which encodes a putative 28.9-kDa basic
      protein with characteristics of DNA-binding proteins, appeared to be involved in
      replication of the plasmid in BCG. By separation of ORF2 and the putative ori
      region, it was revealed that the relative locations of ORF2 and the putative ori
      region are likely important for replication in BCG. No DNA or amino acid
      homologies were found between this replication region and that of pAL5000,
      another mycobacterial plasmid used for vector plasmid construction. In addition,
      we found that this replicon did not lead to replication in E. coli and was
      compatible in BCG with pAL5000-derived vector plasmid pYUB75 (R. G. Barletta, D.
      D. Kim, S. B. Snapper, B. R. Bloom, and W. R. Jacobs, J., J. Gen. Microbiol.
      138:23-30, 1992).

PMID- 8288538
TI  - Glycine betaine confers enhanced osmotolerance and cryotolerance on Listeria
      monocytogenes.
AB  - Listeria monocytogenes is a gram-positive food-borne pathogen that is notably
      resistant to osmotic stress and can grow at refrigerator temperatures. These two
      characteristics make it an insidious threat to public health. Like several other
      organisms, L. monocytogenes accumulates glycine betaine, a ubiquitous and
      effective osmolyte, intracellularly when grown under osmotic stress. However, it
      also accumulates glycine betaine when grown under chill stress at refrigerator
      temperatures. Exogenously added glycine betaine enhances the growth rate of
      stressed but not unstressed cells, i.e., it confers both osmotolerance and
      cryotolerance. Both salt-stimulated and cold-stimulated accumulation of glycine
      betaine occur by transport from the medium rather than by biosynthesis. Direct
      measurement of glycine betaine uptake shows that cells transport betaine 200-fold
      faster at high salt concentration (4% NaCl) than without added salt and 15-fold
      faster at 7 than at 30 degrees C. The kinetics of glycine betaine transport
      suggest that the two transport systems are indistinguishable in terms of affinity
      for betaine and may be the same. Hyperosmotic shock and cold shock experiments
      suggest the transport system(s) to be constitutive; activation was not blocked by
      chloramphenicol. A cold-activated transport system is a novel observation and has
      intriguing implications concerning the physical state of the cell membrane at low
      temperature.

PMID- 8288539
TI  - Cloning, sequencing, and expression of thermophilic Bacillus sp. strain TB-90
      urease gene complex in Escherichia coli.
AB  - The urease of thermophilic Bacillus sp. strain TB-90 is composed of three
      subunits with molecular masses of 61, 12, and 11 kDa. By using synthetic
      oligonucleotide probes based on N-terminal amino acid sequences of each subunit,
      we cloned a 3.2-kb EcoRI fragment of TB-90 genomic DNA. Moreover, we cloned two
      other DNA fragments by gene walking starting from this fragment. Finally, we
      reconstructed in vitro a 6.2-kb DNA fragment which expressed catalytically active
      urease in Escherichia coli by combining these three DNA fragments. Nucleotide
      sequencing analysis revealed that the urease gene complex consists of nine genes,
      which were designed ureA, ureB, ureC, ureE, ureF, ureG, ureD, ureH, and ureI in
      order of arrangement. The structural genes ureA, ureB, and ureC encode the 11-,
      12-, and 61-kDa subunits, respectively. The deduced amino acid sequences of UreD,
      UreE, UreF, and UreG, the gene products of four accessory genes, are homologous
      to those of the corresponding Ure proteins of Klebsiella aerogenes. UreD, UreF,
      and UreG were essential for expression of urease activity in E. coli and are
      suggested to play important roles in the maturation step of the urease in a co-
      and/or posttranslational manner. On the other hand, UreH and UreI exhibited no
      significant similarity to the known accessory proteins of other bacteria.
      However, UreH showed 23% amino acid identity to the Alcaligenes eutrophus HoxN
      protein, a high-affinity nickel transporter.

PMID- 8288540
TI  - Site-directed mutagenesis of the mecA gene from a methicillin-resistant strain of
      Staphylococcus aureus.
AB  - The mecA-27r gene from Staphylococcus aureus 27r encodes penicillin-binding
      protein 2a (PBP2a-27r), which causes this strain to be methicillin resistant.
      Removal or replacement of the N-terminal transmembrane domain had no effect on
      binding of penicillin, but removal of portions of the putative transglycosylase
      domain (144, 245, or 341 amino acids after the transmembrane region) destroyed
      penicillin-binding activity. The SXXK, SXN, and KSG motifs, present in all
      penicillin-interacting enzymes, were found in the expected linear spatial
      arrangement within the putative transpeptidase region of PBP2a-27r. Alterations
      of amino acids in all three of these motifs resulted in elimination of penicillin
      binding activity, confirming their roles in the interaction with penicillin.

PMID- 8288541
TI  - CDP-6-deoxy-delta 3,4-glucoseen reductase from Yersinia pseudotuberculosis:
      enzyme purification and characterization of the cloned gene.
AB  - The 3,6-dideoxyhexoses, usually confined to the cell wall lipopolysaccharide of
      gram-negative bacteria, are essential to serological specificity and are formed
      via a complex biosynthetic pathway beginning with CDP-D-hexoses. In particular,
      the biosynthesis of CDP-ascarylose, one of the naturally occurring 3,6
      dideoxyhexoses, consists of five enzymatic steps, with CDP-6-deoxy-delta 3,4
      glucoseen reductase (E3) participating as the key enzyme in this catalysis. This
      enzyme has been previously purified from Yersinia pseudotuberculosis by an
      unusual procedure (protocol I) including a trypsin digestion step (O. Han, V.P.
      Miller, and H.-W. Liu, J. Biol. Chem. 265:8033-8041, 1990). However, the cloned
      gene showed disparity with the expected gene characteristics, and upon
      expression, the resulting gene product exhibited no E3 activity. These findings
      strongly suggested that the protein isolated by protocol I may have been
      misidentified as E3. A reinvestigation of the purification protocol produced a
      new and improved procedure (protocol II) consisting of DEAE-Sephacel, phenyl
      Sepharose, Cibacron blue A, and Sephadex G-100 chromatography, which efficiently
      yielded a new homogeneous enzyme composed of a single polypeptide with a
      molecular weight of 39,000. This highly purified protein had a specific activity
      nearly 8,000-fold higher than that of cell lysates, and more importantly, the
      corresponding gene (ascD) was found to be part of the ascarylose biosynthetic
      cluster. Presented are the identification and confirmation of the E3 gene through
      cloning and overexpression and the culminating purification and unambiguous
      assignment of homogeneous E3. The nucleotide and translated amino acid sequences
      of the genuine E3 are also presented.

PMID- 8288542
TI  - Expression of both Bacillus subtilis threonyl-tRNA synthetase genes is
      autogenously regulated.
AB  - The "housekeeping" threonyl-tRNA synthetase gene (thrS) of Bacillus subtilis is
      shown to be transcribed in vivo and in vitro from a single promoter. In vitro,
      85% of all messages transcribed from the thrS promoter are terminated at a strong
      factor-independent terminator localized upstream of the thrS Shine-Dalgarno
      sequence, within the 305-nucleotide-long leader region. Overexpression of thrS
      represses transcriptional and translational thrS-lacZ fusions to a similar
      extent, suggesting that thrS is autoregulated at the transcriptional level. We
      show that autogenous control does not act at the level of transcription
      initiation but involves antitermination of the transcription mechanism. thrZ, the
      second threonyl-tRNA synthetase gene, is also autogenously regulated. However,
      the ability of the ThrS synthetase to repress thrS as well as thrZ expression is
      much greater than that of the ThrZ synthetase.

PMID- 8288543
TI  - Opine-regulated promoters and LysR-type regulators in the nopaline (noc) and
      octopine (occ) catabolic regions of Ti plasmids of Agrobacterium tumefaciens.
AB  - Essential steps in the uptake and catabolism of the plant tumor metabolites
      nopaline and octopine in Agrobacterium spp. are performed by proteins encoded in
      the nopaline catabolic (noc) and octopine catabolic (occ) regions of Ti plasmids.
      We investigated the opine activation of the genes by using (i) promoter studies
      of Agrobacterium spp. and (ii) analysis of the promoter interaction with the
      regulatory proteins NocR (noc) and OccR (occ). The noc region contained two
      nopaline-induced promoters (Pi1[noc] and Pi2[noc]) and one autogenously regulated
      promoter (Pr [control of NocR expression]). Pi2 and Pr overlapped and were
      divergently oriented (Pi2 [noc]). DNA binding studies and DNase I footprints
      indicated that NocR bound specifically to single binding sites in Pi1[noc] and
      Pi2/Pr[noc] and that Pi2 and Pr were regulated from the same binding site. The
      binding was independent of the inducer nopaline, and nopaline caused small
      changes in the footprint. The promoters in the noc and occ regions shared
      sequence motif and contained the sequence T-N11-A, which is characteristic for
      LysR-type-regulated promoters. The occ region contained one octopine-induced and
      one autogenously regulated promoter (Pi/Pr[occ]) in the same arrangement as
      Pi2/Pr[noc] in the noc region. Promoter deletions indicated that sequences
      flanking the OccR binding site determined the extent of induction, although they
      did not bind OccR. The promoter bound OccR in the absence and presence of
      octopine. The opine caused a change in the mobility of the DNA-protein complex
      with the complete promoter. The resected fragments did not reveal this opine
      induced shift, and it was also not detectable with the DNA-NocR complexes with
      the two promoters of the noc region.

PMID- 8288544
TI  - Characterization of the gene encoding hydroxylamine oxidoreductase in
      Nitrosomonas europaea.
AB  - Hydroxylamine oxidoreductase (HAO) catalyzes the oxidation of hydroxylamine to
      nitrite in Nitrosomonas europaea. The electrons released in the reaction are
      partitioned to ammonium monooxygenase and to the respiratory chain. The immediate
      acceptor of electrons from HAO is believed to be cytochrome c-554 (Cyt c-554). We
      have isolated a genomic DNA fragment containing the structural gene encoding HAO
      (hao) and a part of the gene for Cyt c-554. The nucleotide sequence of hao was
      determined, and its transcription was analyzed. The open reading frame (ORF)
      encodes amino acid sequences matching the purified peptides of HAO. A 64.28-kDa
      protein is encoded in this ORF, in close agreement with the empirically
      determined molecular mass of 63 kDa. The N terminus was located 24 amino acids
      from the start codon, suggesting the presence of a leader sequence. The putative
      eight heme-binding peptides were localized in this ORF. The gene for Cyt c-554
      was located 1,200 bp downstream from the 3' end of hao. An ORF was identified in
      the upstream region from hao and may encode a protein of unknown function. Data
      bank searches did not reveal proteins with substantial similarities to HAO, but
      they did reveal similarities between Cyt c-554 and other c-type cytochromes.

PMID- 8288545
TI  - Catabolite repression of the Bacillus subtilis gnt operon mediated by the CcpA
      protein.
AB  - Inducer exclusion was not important in catabolite repression of the Bacillus
      subtilis gnt operon. The CcpA protein (also known as AlsA) was found to be
      necessary for catabolite repression of the gnt operon, and a mutation (crsA47,
      which is an allele of the sigA gene) partially affected this catabolite
      repression.

PMID- 8288546
TI  - Strain identification and 5S rRNA gene characterization of the hyperthermophilic
      archaebacterium Sulfolobus acidocaldarius.
AB  - A commonly used laboratory Sulfolobus strain has been unambiguously identified as
      Sulfolobus acidocaldarius DSM639. The 5S rRNA gene from this strain was cloned
      and sequenced. It differs at 17 of 124 positions from the identical 5S rRNA
      sequences from Sulfolobus solfataricus and a strain apparently misidentified as
      S. acidocaldarius. Analysis of the transcripts from the 5S rRNA gene failed to
      identify any precursor extending a significant distance beyond the 5' or 3'
      boundary of the 5S rRNA-coding sequence. This result suggests that the primary
      transcript of the 5S rRNA gene corresponds in length (within 1 or 2 nucleotides)
      to the mature 5S rRNA sequence found in 50S ribosomal subunits.

PMID- 8288547
TI  - An insertional point mutation inactivates NolR repressor in Rhizobium meliloti
      1021.
AB  - In the majority of Rhizobium meliloti isolates, nod gene expression is controlled
      by NolR, but this is not the case in a few strains including the widely used
      laboratory strain 1021. In 1021, the lack of NolR function was shown to be due to
      a single insertional mutation in the C-terminal coding sequence which abolished
      the DNA-binding ability, though the helix-turn-helix motif remained intact. This
      indicates that the C-terminal part of the protein is also essential for DNA
      binding. We conclude that in this species, control of nod gene expression
      involves NolR and strain 1021 represents an exception in which the NolR function
      was lost by a single event.

PMID- 8288548
TI  - Zinc, a structural component of adenylate kinases from gram-positive bacteria.
AB  - The recent finding that Bacillus stearothermophilus adenylate kinase contains a
      zinc atom coordinated to four cysteines prompted us to investigate the metal
      binding properties of the enzyme from various bacteria. We conclude that zinc was
      present only in adenylate kinase from gram-positive species and that this
      property is correlated with the presence of three or four Cys residues in the
      sequence Cys-X2-Cys-X16-Cys-X2-Cys/Asp, in which X stands for different amino
      acid residues.

PMID- 8288549
TI  - Properties of a Streptococcus salivarius spontaneous mutant in which the
      methionine at position 48 in the protein HPr has been replaced by a valine.
AB  - HPr is a protein of the phosphoenolpyruvate:sugar phosphotransferase system (PTS)
      that participates in the concomitant transport and phosphorylation of sugars in
      bacteria. In gram-positive bacteria, HPr is also reversibly phosphorylated at a
      seryl residue at position 46 (Ser-46) by a metabolite-activated ATP-dependent
      kinase and a Pi-dependent HPr(Ser-P) phosphatase. We report in this article the
      isolation of a spontaneous mutant (mutant A66) from a streptococcus
      (Streptococcus salivarius) in which the methionine at position 48 (Met-48) in the
      protein HPr has been replaced by a valine (Val). The mutation inhibited the
      phosphorylation of HPr on Ser-46 by the ATP-dependent kinase but did not prevent
      phosphorylation of HPr by enzyme I or the phosphorylation of enzyme II complexes
      by HPr(His-P). The results, however, suggested that replacement of Met-48 by Val
      decreased the affinity of enzyme I for HPr or the affinity of enzyme II proteins
      for HPr(His-P) or both. Characterization of mutant A66 demonstrated that it has
      pleiotropic properties, including the lack of IIILman, a specific protein of the
      mannose PTS; decreased levels of HPr; derepression of some cytoplasmic proteins;
      reduced growth on PTS as well as on non-PTS sugars; and aberrant growth in medium
      containing a mixture of sugars.

PMID- 8288550
TI  - Regulation of the Escherichia coli hfq gene encoding the host factor for phage Q
      beta.
AB  - The host factor (HF-I) for phage Q beta RNA replication is a small protein of 102
      amino acid residues encoded by the hfq gene at 94.8 min on the Escherichia coli
      chromosome. The synthesis rate of HF-I at the exponential-growth phase is higher
      than at the stationary phase, and it increases concomitantly with the increase in
      cell growth rate. The intracellular level of HF-I is about 30,000 to 60,000
      molecules per cell, the majority being associated with ribosomes as one of the
      salt wash proteins. Taken together, we suggest that HF-I is one of the growth
      related proteins.

PMID- 8288551
TI  - Efficient transposition in mycobacteria: construction of Mycobacterium smegmatis
      insertional mutant libraries.
AB  - The Tn611 transposon was inserted into pCG63, a temperature-sensitive plasmid
      isolated from an Escherichia coli-mycobacterial shuttle vector which contains the
      pAL5000 and pUC18 replicons. The resulting plasmid, pCG79, was used to generate a
      large number of insertional mutations in Mycobacterium smegmatis. These are the
      first mycobacterial insertional mutant libraries to be constructed by
      transposition directly into a mycobacterium. No highly preferential insertion
      sites were detected by Southern blot analysis of the chromosomal DNAs isolated
      from the insertion mutants. Auxotrophic mutants with various phenotypes were
      isolated at a frequency ranging from 0.1 to 0.4%, suggesting that the libraries
      are representative. The pCG79 system thus seems to be a useful tool for the study
      of M. smegmatis genetics and may be applicable to other mycobacteria, such as the
      M. tuberculosis complex.

PMID- 8288552
TI  - Mutations in the delta subunit influence the assembly of F1F0 ATP synthase in
      Escherichia coli.
AB  - Missense mutations affecting Asp-161 and Ser-163 in the delta subunit of F1F0 ATP
      synthase have been generated. Although most substitutions allowed substantial
      enzyme function, the delta Asp-161-->Pro substitution resulted in a loss of
      enzyme activity. The loss of activity was attributable to a structural failure
      altering assembly of the enzyme complex.

PMID- 8288553
TI  - Regulation of the raffinose permease of Escherichia coli by the glucose-specific
      enzyme IIA of the phosphoenolpyruvate:sugar phosphotransferase system.
AB  - In enteric bacteria, chromosomally encoded permeases specific for lactose,
      maltose, and melibiose are allosterically regulated by the glucose-specific
      enzyme IIA of the phosphotransferase system. We here demonstrate that the plasmid
      encoded raffinose permease of enteric bacteria is similarly subject to this type
      of inhibition.

PMID- 8288554
TI  - Isolation and characterization of the mouse heme oxygenase-1 gene. Distal 5'
      sequences are required for induction by heme or heavy metals.
AB  - Mouse genomic fragments encoding heme oxygenase-1 (HO-1) were isolated from a
      recombinant lambda library by in situ plaque hybridization. The mouse HO-1 gene,
      approximately 7 kilobase pairs (kbp) in length, is organized into 5 exons and 4
      introns. The primary structure of the exons and 1287 base pairs (bp) of the 5'
      flanking region was determined. The deduced amino acid sequence of the mouse HO-1
      gene is identical to that of p32, initially identified as a stress-induced
      protein in mouse BALBc/3T3 cells. A single, major transcription initiation site
      is utilized for constitutive and heme- or metal-induced expression of the HO-1
      gene in mouse hepatoma (Hepa) cells. The transcriptional activity of the 5'
      flanking region was examined by transient expression assays using the
      chloramphenicol acetyltransferase gene as the reporter gene. Basal promoter
      activity in several cell lines was localized to within 149 bp of the upstream
      sequence by deletion analysis. This proximal promoter region of the mouse HO-1
      gene contains several sequence elements that are not only conserved in both the
      rat and human HO-1 genes but also resemble consensus binding sites of various
      transcription factors including AP-1, AP-4, C/EBP and c-Myc:Max/USF. Heavy metals
      activate HO-1 gene transcription and the rat gene contains a putative metal
      regulatory element (Muller, R. M., Taguchi, H., and Shibahara, S. (1987) J. Biol.
      Chem. 262, 6795-6802) that is completely conserved in the mouse gene. Transient
      expression analyses, however, indicate that this sequence, which contains a core
      heptanucleotide, TGCACTC, identical to that of the strongest metal regulatory
      element of the mouse metallothionein-1 gene, is not responsive to Cd2+ or Zn2+.
      Stable transfection of constructs containing the entire mouse HO-1 gene and
      various portions of the 5'-flanking region into rat C6 glioma cells and
      simultaneous, quantitative analysis of the mouse and rat HO-1 mRNAs indicate that
      distal 5' sequences, between positions -3.5 and -12.5 kbp, are required for
      induction of mouse HO-1 gene transcription by both heme and heavy metals. A 5-7
      fold difference in the levels of induction between stably integrated and
      transiently expressed mouse HO-1 gene constructs is observed in this cell
      line.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8288555
TI  - Heme-heme oxygenase complex. Structure of the catalytic site and its implication
      for oxygen activation.
AB  - Heme oxygenase, a central monooxygenase enzyme of the heme catabolism and the
      associated generation of carbon monoxide, forms a 1:1 stoichiometric complex with
      iron protoporphyrin IX, which is a prosthetic active center and at the same time
      the substrate of the enzyme. By using EPR, resonance Raman, and optical
      absorption spectroscopic techniques, we have determined the axial ligand
      coordination of the enzyme-heme complex. The ferric heme iron in the heme-enzyme
      complex at neutral pH is six-coordinate high spin, while at alkaline pH (pKa
      7.6), the complex becomes low spin. Spectra of ferrous forms of the complex
      indicate that histidine serves as the iron proximal axial ligand and that the
      residue is in its neutral imidazole rather than its imidazolate protonation
      state. Thus, the active site of the heme-heme oxygenase complex has a myoglobin
      like structure rather than an active site similar to the large cytochrome P-450
      class of monooxygenases. As a consequence, the activated form of the heme-heme
      oxygenase complex, a peroxo intermediate, is different from that of the
      cytochrome P-450 monooxygenases, in which the activated form is an oxo
      intermediate. The overall catalytic mechanism is probably more closely related to
      that of other monooxygenases with myoglobin-like active sites, such as secondary
      amine monooxygenase.

PMID- 8288556
TI  - Identification of probasin-related antigen as cystathionine gamma-lyase by
      molecular cloning.
AB  - We reported previously that a monoclonal antibody against probasin (rat prostatic
      secretory protein) recognizes a 40-kDa protein localized in rat liver and kidney.
      The protein (probasin-related antigen, PRB-RA) may participate in a specific
      differentiated function of these tissues. To clarify the molecular nature of PRB
      RA, a series of cDNA clones coding for the protein were isolated from a rat liver
      expression library using an affinity-purified polyclonal antibody. The amino acid
      sequence deduced from the determined cDNA sequence included sequences identical
      with those of proteolytic fragments of PRB-RA, which covered about 70% of the
      deduced sequence. Northern blot hybridization of poly(A)+ RNA isolated from rat
      tissues showed the presence of predominant and minor mRNA species of about 2.0
      and 4.3 kilobases, respectively, in the liver and kidney. A sequence homology
      search revealed that PRB-RA is almost completely identical to rat cystathionine
      gamma-lyase (cystathionase) and that it does not show overall homology with
      probasin. Three candidates for an epitope common to probasin and PRB-RA were
      found on close examination of the amino acid sequences of the two proteins. A
      synthetic peptide, TYFRRI, corresponding to one of the candidates, neutralized
      the reactivity of the anti-probasin monoclonal antibody to both probasin and PRB
      RA on Western blot analysis. These results show that PRB-RA/cystathionase is
      neither structurally nor functionally related to probasin except for a common
      epitope and that cystathionase, a cystein-producing enzyme, is localized in
      urinary tubular epithelial cells in a highly restricted region of the kidney in
      addition to in liver parenchymal cells.

PMID- 8288557
TI  - Kinetic studies on the removal of extracellular hydrogen peroxide by cultured
      fibroblasts.
AB  - To investigate the function of antioxidant enzymes in intact cells, we examined
      the removal of extracellular H2O2 by cultured fibroblasts (IMR-90). H2O2
      concentration dependence of the reaction rate was interpreted as that the process
      involves two kinetically different reactions (referred to as reactions 1 and 2).
      Reaction 1 was characterized by a relatively low Km value (about 40 microM), and
      reaction 2 by linear dependence of the rate up to 500 microM H2O2. The magnitude
      of reaction 1 was reduced by treatment of the cells with diethyl maleate or 6
      amino-nicotinamide, while reaction 2 was inhibited by 3-amino-1,2,4-triazole
      treatment. It was concluded that reactions 1 and 2 are principally due to GSH
      peroxidase and catalase, respectively. The values of kinetic parameters were
      estimated by curve-fitting, and it was inferred that 80 to 90% of H2O2 is
      decomposed by GSH peroxidase at H2O2 concentrations lower than 10 microM. The
      contribution of catalase increases with the increase in H2O2 concentration. The
      intact cells showed a low catalase activity (about 15%), as compared with the
      activity found in the solubilized cells. The low catalase activity was ascribed
      to the latency of the enzyme caused by localization in peroxisomes. Fibroblasts
      also removed intracellular H2O2 generated by menadione. Treatment with diethyl
      maleate greatly impaired the H2O2-removing capability and caused H2O2 efflux into
      the medium.

PMID- 8288558
TI  - Ascorbic acid and insulin secretion in pancreatic islets.
AB  - The effect of ascorbic acid on glucose-induced insulin release from single
      pancreatic islets was measured using a new, ultra-sensitive enzyme-linked
      immunosorbent insulin assay. Within 20 s ascorbic acid inhibited insulin
      secretion; inhibition was dose dependent and completely reversible. There was a
      50% inhibition of the secretory response with 200 microM ascorbic acid and 90%
      inhibition with 400 microM ascorbic acid. The decrease in insulin secretion was
      recorded as a reduction of the amplitudes of the fast insulin transients, which
      give rise to the oscillatory nature of insulin secretion. The inhibition of
      glucose-induced insulin release by ascorbic acid was associated with
      hyperpolarization of the pancreatic beta-cell. Suppression of glucose-induced
      membrane depolarization was evident after 20 s, was dose dependent, and was
      completely reversible. The data here may provide the first explanation of why
      plasma ascorbate concentrations are tightly controlled.

PMID- 8288559
TI  - Regulation of the glial-specific JC virus early promoter by the transcription
      factor Sp1.
AB  - The regulation of glial-specific JC virus early gene expression was addressed by
      functional dissection of a previously uncharacterized form of the JC virus
      promoter (MH-1). The MH-1 promoter directed 31-fold higher reporter gene
      expression in U87MG glioma cells than in HeLa cells in a transient transfection
      assay. Transfection of promoter constructs containing proximal or proximal plus
      upstream regions revealed that reporter gene expression was activated by both
      proximal and tandem repeat regions in glioma cells. The proximal region contains
      a guanine-rich sequence, the GA box, which was found to regulate the promoter,
      and was recognized specifically by the transcription factor Sp1. The GA box is
      also present in the promoters of three glial-specific cellular genes. Together
      with paired AP-1 and NF-1 sites in the tandem repeats, the GA box is part of a
      motif that is conserved between several glial-specific promoters, and is thus a
      potential determinant of glial-specific gene expression. These results delineate
      the promoter regions required for activation of the MH-1 JC virus promoter,
      suggest a new determinant of glial specificity, and establish a model for the
      investigation of combinatorial activation of a glial-specific viral promoter.

PMID- 8288560
TI  - Low affinity acceleration of the phosphorylation reaction of the Na,K-ATPase by
      ATP.
AB  - The maximum rate of phosphorylation (rm) of a highly purified Na,K-ATPase from
      red outer medulla of pig kidney was measured at 25 degrees C as a function of ATP
      concentration in media with Mg2+, Na+, and no K+. When rm was plotted as a
      function of the concentration of ATP a biphasic response was observed with a
      hyperbolic component of high affinity (Km = 15.7 +/- 2.6 microM) and low velocity
      ((rm)max = 460 +/- 40 nmol of Pi/(mg of protein.s)) plus a parabolic component
      which showed no saturation up to 1000 microM ATP, concentration at which rm was
      1768.1 +/- 429.6 nmol Pi/(mg protein.s) (mean +/- S.E.; n = 3). This low affinity
      effect of ATP on the rate of phosphorylation disappeared when the Na,K-ATPase
      underwent turnover in medium without K+ suggesting that, like
      superphosphorylation (Peluffo, R. D., Garrahan, P. J., and Rega, A. F. (1992) J.
      Biol. Chem. 267, 6596-6601), it required the enzyme to be at rest. This property
      of the Na,K-ATPase was not predicted by the Albers-Post reaction scheme. The
      observed behavior of the enzyme could be simulated by a scheme that involves a
      resting enzyme (Er) functionally different from E1 or E2, which is able to bind
      three molecules of ATP, one with high and two with low affinity, and that after
      phosphorylation is converted into the phosphointermediates that are generally
      considered to participate in the reaction cycle described by Albers and Post.

PMID- 8288561
TI  - Stabilization of the EBNA1 protein on the Epstein-Barr virus latent origin of DNA
      replication by a DNA looping mechanism.
AB  - DNA replication from the Epstein-Barr virus latent origin of replication, oriP,
      is activated by Epstein-Barr nuclear antigen 1 (EBNA1). This activation involves
      the binding of EBNA1 dimers to multiple sites present in the two noncontiguous
      functional elements of oriP, the dyad symmetry element (DS) from which
      replication initiates, and the family of repeats (FR) enhancer element. EBNA1
      complexes formed on the FR and DS elements of oriP interact by a DNA looping
      mechanism. This interaction requires EBNA1 sequences in addition to those
      required for DNA binding and dimerization. To map the EBNA1 sequences required
      for the efficient interaction of FR- and DS-bound EBNA1 complexes, we have
      overproduced in Escherichia coli and purified a series of EBNA1 N-terminal
      truncation mutants, all of which retain the DNA binding and dimerization domains.
      The results of electron microscopy and ligation-enhancement assays using these
      mutants indicated that EBNA1 sequences between amino acids 350 and 361 are
      required for the efficient interaction of FR- and DS-bound EBNA1 complexes. EBNA1
      mediated FR-DS interactions were shown to stabilize EBNA1 binding to the DS
      element, while EBNA1-mediated DS-DS interactions did not. These results suggest
      that the stabilization of EBNA1 on the DS element, which occurs as a result of
      EBNA1-mediate oriP looping, may be important for the activation of DNA
      replication from the DS element.

PMID- 8288562
TI  - Replacement of alanine 58 by asparagine enables the melibiose carrier of
      Klebsiella pneumoniae to couple sugar transport to Na+.
AB  - The melibiose carrier of Klebsiella pneumoniae couples sugar transport to H+ and
      Li+, while that of Escherichia coli uses Na+ besides the other two cation species
      (Hama and Wilson, 1992). We have shown that the K. pneumoniae melibiose carrier
      is capable of recognizing Na+ when the amino-terminal 81 residues are replaced by
      the corresponding region of the E. coli melibiose carrier (Hama and Wilson,
      1993). In this amino-terminal region there are 5 residues that are not conserved
      between the two carriers. In this study, we changed each of the 5 residues of the
      K. pneumoniae carrier to the one in the E. coli carrier. The substitutions are
      Ile-36-->Val, Val-43-->Leu, Leu-54-->Trp, Ala-58-->Asn, and Cys-68-->Ala. With
      four of the five mutants, Ile-36-->Val, Val-43-->Leu, Leu-54-->Trp, and Cys-68-
      >Ala, sugar accumulation was not affected by Na+. In striking contrast, melibiose
      and methyl-1-thio-beta-D-galactopyranoside accumulation was greatly stimulated by
      Na+ with the Ala-58-->Asn mutant. Furthermore, Na+ uptake coupled to downhill
      melibiose transport was observed with the Ala-58-->Asn mutant. These results
      indicate that the Ala-58-->Asn substitution enables the K. pneumoniae melibiose
      carrier to couple sugar transport to Na+. It is clear that the Asn-58 residue
      (Asn-54 in the E. coli carrier) is involved in Na+ recognition.

PMID- 8288563
TI  - Identification and characterization of a novel tyrosine kinase from
      megakaryocytes.
AB  - Protein-tyrosine kinases play pivotal roles in cell signal transduction. We have
      isolated a cDNA clone encoding a novel human intracytoplasmic tyrosine kinase,
      termed matk (megakaryocyte-associated tyrosine kinase). Expression of matk mRNA
      was predominantly found in cells of megakaryocytic lineage. The matk cDNA clone
      encodes a polypeptide of 527 amino acids and has closest sequence similarity to
      the csk tyrosine kinase. Sequence comparisons also indicate that matk contains
      src homology region 2 and 3 domains but lacks the NH2-terminal myristylation
      signal, the negative regulatory tyrosine (Tyr-527), and the autophosphorylation
      site (Tyr-416) corresponding to those found in src. Antibodies raised against the
      NH2 terminus of matk immunoprecipitated a 60-kDa protein from the CMK human
      megakaryocyte cell line. Expression of matk mRNA was up-regulated in
      megakaryocytic cells induced to differentiate by the phorbol ester. Based on its
      restriction in expression and its modulation during in vitro differentiation, it
      is likely that matk participates in signal transduction during
      megakaryocytopoiesis.

PMID- 8288564
TI  - Enzymatic methylation of recombinant heterogeneous nuclear RNP protein A1. Dual
      substrate specificity for S-adenosylmethionine:histone-arginine N
      methyltransferase.
AB  - We have previously reported the existence of two different molecular species of
      protein methylase I (S-adenosylmethionine:protein-arginine N-methyltransferase,
      E.C. 2.1.1.23) in calf brain, one specific for myelin basic protein and the other
      for histone (Ghosh, S. K., Paik, W. K., and Kim, S. (1988) J. Biol. Chem. 263,
      19024-19033). In the present study, however, we report that heterogeneous
      ribonucleoprotein particle protein A1 is most likely an in vivo substrate for the
      "histone-specific protein methylase I." The unmethylated recombinant protein A1
      has been found to be a much superior methyl acceptor for the enzyme than histone
      with a Km value two orders of magnitude lower (0.19 microM) than that for histone
      (21 microM). Myelin basic protein, a specific inhibitor for histone protein
      methylase I, exhibited a lower IC50 for protein A1 methylation (IC50 = 33 microM)
      compared with histone methylation (IC50 = 220 microM) and competitively inhibited
      the former with a Ki value of 1.3 x 10(-6) M. The extent of inhibition of protein
      A1 and histone methylation by the polyclonal antibodies prepared against purified
      "histone protein methylase I" was identical. Maximally, 1.08-mol methyl groups
      were incorporated per mol of protein A1, which was 27-fold higher than that of
      histone (0.04 mol/mol of histone). HPLC analysis of the enzymatically methylated
      amino acid residues in protein A1 revealed the formation of NG-monomethylarginine
      and NG,NG-dimethylarginine. The ratio of NG,NG-dimethylarginine/NG
      monomethylarginine increased as a function of incubation period; however, NG,N'G
      dimethylarginine was not detectable. Proteolytic cleavage of the methyl-3H
      labeled recombinant protein A1 by trypsin and Staphylococcus aureus V8
      endoprotease indicated that protein A1 possesses multiple sites for methylation,
      one of which was identified as residue 194 arginine, which coincided with the in
      vivo methylation site.

PMID- 8288565
TI  - 1H NMR study of the solution molecular and electronic structure of engineered
      distal myoglobin His64(E7) Val/Val68(E11) His double mutant. Coordination of
      His64(E11) at the sixth position in both low-spin and high-spin states.
AB  - A genetically engineered human myoglobin (Mb) in which the distal His, His64(E7),
      and the distal Val, Val68(E11), are replaced by Val and His, respectively, has
      been expressed in Escherichia coli, for the purpose of assessing the potential
      role of a E11 residue in providing a hydrogen bond donor to the coordinated
      ligand. Molecular modeling indicates that such an interaction is possible. The 1H
      NMR spectrum of the ferric form of the double mutant Mb exhibits large hyperfine
      shifts and strong paramagnetic relaxation for which the temperature dependence of
      the hyperfine shifts reveals a thermal equilibrium between a low-spin and high
      spin state (70, 30% at 25 degrees C, respectively). Standard sequence specific
      two-dimensional (2D) NMR assignments of the E and F helical backbones allow the
      identification of the peptide protons for the proximal His93(F8) and substituted
      distal His68(E11). Steady-state nuclear Overhauser effect from these peptide
      protons locate strongly hyperfine shifted His93(F8) and His68(E11) side chain
      protons which dictate that both the imidazole rings are coordinated to the iron.
      2D bond correlation and one-dimensional and 2D dipolar correlation experiments
      locate and assign the resonances for the heme. The pattern of the heme contact
      shifts in both the low-spin and high-spin state, together with the nature of the
      temperature dependence of the His93(F8) and His68(E11) resonances, establish that
      the two His are ligated in the high-spin as well as low-spin forms. The pattern
      of heme methyl hyperfine shifts in the low-spin state, and the smaller hyperfine
      shifts for His68(E11) as compared to His93(F8) in the high-spin state, indicate
      that the axial bond to the distal His68(E11) is weakened or strained as compared
      with that for the proximal His93(F8) in both spin states. This weak ligation
      originates from a tilted iron-His68 bond, the only conformation in which His68
      can place its imidazole group sufficiently close to bind to the heme iron in the
      conventional Mb folding. Not only do these results support the belief that distal
      His is indispensable for the control of the ligand binding in Mb and hemoglobin,
      but also reveal the significance of the evolution that the stereochemical
      disposition of both His64 and Val68 are unique and non-exchangeable for
      interacting with the bound ligand.

PMID- 8288566
TI  - IFP 35 is an interferon-induced leucine zipper protein that undergoes interferon
      regulated cellular redistribution.
AB  - We have isolated a new human cDNA, named IFP 35, whose expression is regulated by
      interferons (IFN). Induction of IFP 35 mRNA in HeLa cells by IFN is due, at least
      in part, to increased transcription. In response to IFN treatment, the expression
      of IFP 35 mRNA is seen in a wide range of different cell types, including
      fibroblasts, macrophages, and epithelial cells. The cDNA sequence encodes a 282
      amino acid protein with a deduced molecular mass of 31,130 Da. In vitro
      translation of mRNA obtained by both in vitro transcription and hybrid selection
      resulted in the synthesis of a 35-kDa protein. Antisera raised against IFP 35
      recognized a protein with an apparent molecular mass of 35 kDa in HeLa cells.
      Amino acid sequence analysis revealed a leucine zipper motif in an alpha-helical
      configuration at the extreme amino terminus of IFP 35. Notable IFP 35 is a unique
      novel leucine zipper protein in that it lacks a basic domain critical for DNA
      binding. IFP 35 can specifically form homodimers in vitro. Western blot analysis
      of fractionated cell extracts indicates increased nuclear localization following
      IFN treatment.

PMID- 8288567
TI  - Expression, purification, and characterization of the G protein-coupled receptor
      kinase GRK5.
AB  - G protein-coupled receptor kinases (GRKs) such as rhodopsin kinase and the beta
      adrenergic receptor kinase (beta ARK) play an important role in agonist-specific
      phosphorylation and desensitization of G protein-coupled receptors. GRK5 is a
      recently identified member of the GRK family that has greater homology with
      rhodopsin kinase than with beta ARK. To further characterize the activity of
      GRK5, it has been overexpressed in Sf9 insect cells and purified by successive
      chromatography on S-Sepharose and Mono S columns. GRK5 phosphorylates the beta 2
      adrenergic receptor (beta 2AR), m2 muscarinic cholinergic receptor, and rhodopsin
      in an agonist-dependent manner to maximal stoichiometries of approximately 2.5,
      1.5, and 1 mol of phosphate/mol of receptor, respectively, with Km values of
      approximately 0.5 microM for the beta 2AR, approximately 16 microM for rhodopsin,
      and approximately 24 microM for ATP. Peptide phosphorylation studies suggest that
      in contrast to beta ARK and rhodopsin kinase, GRK5 preferentially phosphorylates
      on nonacidic peptides with a Km of approximately 1.5 mM. Heparin and dextran
      sulfate were found to be potent inhibitors of GRK5 with IC50 values of
      approximately 1 nM, thereby being at least 150-fold more potent on GRK5 than on
      beta ARK. GRK5 can also be activated by polycations, with 10 microM polylysine
      promoting an approximately 2.6-fold activation. Overall, these studies
      demonstrate that GRK5 has unique properties that distinguish it from other
      members of the GRK family and that likely play an important role in modulating
      its mechanism of action.

PMID- 8288568
TI  - Molecular cloning of a possible cysteine proteinase predominantly expressed in
      osteoclasts.
AB  - Osteoclasts are multinucleate giant cells playing key roles in bone resorption.
      These cells solubilize mineralized bone matrix by means of acid and protease
      action; however, the precise mechanism of this process is not well known.
      Recently, we succeeded in the isolation of pure osteoclasts from rabbit bones and
      constructed a cDNA library. Using a differential screening procedure, two genes
      expressed predominantly in osteoclasts compared with spleen cells were isolated
      (Tezuka, K., Sato, T., Kamioka, H., Nijweide, P. J., Tanaka, K., Matsuo, T.,
      Ohta, M., Kurihara, N., Hakeda, Y., and Kumegawa, M. (1992) Biochem. Biophys.
      Res. Commun. 186, 911-917). One of them, OC-2, was found to encode a possible
      cysteine proteinase structurally related to cathepsins L and S. By in situ
      hybridization, OC-2 was confirmed to be expressed in osteoclasts in vivo. By
      Northern blot analysis, OC-2 was highly and preferentially expressed in
      osteoclasts compared with other tissues such as kidney, liver, spleen, and lung.
      The predominant expression of OC-2 in osteoclasts may suggest that OC-2 encodes a
      protein, possibly a cysteine proteinase, that plays an important role in
      osteoclastic bone resorption.

PMID- 8288569
TI  - Cyclic AMP triggers large [Ca2+]i oscillations in glucose-stimulated beta-cells
      from ob/ob mice.
AB  - The modulation of intracellular free calcium concentration ([Ca2+]i) by cAMP was
      compared in pancreatic beta-cells of lean (+/+) and obese (ob/ob) mice. Neither
      forskolin nor 8-bromo-cAMP significantly affected basal [Ca2+]i in unstimulated
      lean and obese mouse beta-cells. In obese, but not in lean mouse beta-cells,
      adding forskolin or 8-bromo-cAMP during the glucose-induced [Ca2+]i response
      triggered external Ca(2+)-dependent [Ca2+]i oscillations with a duration of 5-11
      s and a frequency of 2.3-4.8 min-1. The induction of oscillations by cAMP
      required both a stimulatory glucose concentration and membrane depolarization.
      (Sp)-cAMPS, did induce oscillations in lean mouse beta-cells. However, these
      oscillations were different from those seen in obese mouse beta-cells and
      required higher concentrations of (Sp)-cAMPS. The inducibility of fast
      oscillations in obese mouse beta-cells indicates hypersensitivity of these cells
      to cAMP, and suggests an abnormal behavior of K+ and/or Ca2+ channels.

PMID- 8288570
TI  - Inhibition of thrombin receptor signaling by a G-protein coupled receptor kinase.
      Functional specificity among G-protein coupled receptor kinases.
AB  - The thrombin receptor, a member of the seven membrane-spanning superfamily of G
      protein coupled receptors, is activated by an irreversible proteolytic mechanism,
      but signaling by activated thrombin receptors shuts off soon after receptor
      activation. This shut-off mechanism is thought to be required for concentration
      dependent responses to thrombin and an important determinant of the cell's
      sensitivity to thrombin. We report that the thrombin receptor is rapidly
      phosphorylated upon activation, consistent with the action of a G-protein-coupled
      receptor kinase. Moreover, the G-protein coupled receptor kinase BARK2 (beta
      adrenergic receptor kinase 2) blocked signaling by thrombin receptors coexpressed
      in Xenopus oocytes. In this system, rhodopsin kinase was inactive and BARK1 was
      markedly less effective than BARK2. Thrombin receptor mutants which lacked
      potential serine and threonine phosphorylation sites in the receptor's
      cytoplasmic tail were insensitive to inhibition by exogenous BARK2 but did confer
      concentration-dependent responses to thrombin. Our studies demonstrate that a G
      protein coupled receptor kinase can shut off thrombin receptor signaling but that
      additional mechanism(s) for terminating signaling exist. These studies also
      reveal functional specificity among G-protein coupled receptor kinases in a novel
      in vivo reconstitution system and show that heterologous expression of these
      kinases can be used to manipulate cellular responsiveness.

PMID- 8288571
TI  - Hairpin loop and second kringle domain are essential sites for heparin binding
      and biological activity of hepatocyte growth factor.
AB  - Hepatocyte growth factor (HGF) has a strong affinity for heparin. About one
      fourth of HGF secreted from MRC-5 human embryonic lung fibroblast cells was found
      to be associated with heparin and heparan sulfate proteoglycan on the cell
      surface and extracellular matrix. To identify heparin-binding sites within the
      HGF molecule, we constructed variously deleted mutant HGFs and examined their
      binding ability to an immobilized heparin column. Native HGF and mutant HGFs,
      including d-K1 (deletion of the first kringle domain), d-K3 (deletion of the
      third kringle domain), d-K4 (deletion of the fourth kringle domain), d-beta
      (deletion of beta-chain), and HK1K2 (consisting of the N-terminal hairpin loop
      and the first two kringle domains), tightly bound to a heparin column, but d-H
      (deletion of the N-terminal hairpin loop) and d-K2 (deletion of the second
      kringle domain) markedly decreased binding ability to the column. These
      observations suggest that the N-terminal hairpin loop and the second kringle
      domain are essential for the heparin-binding of HGF. The finding that HK1K2
      competed the binding of 125I-HGF to immobilized heparin provided additional
      evidence that the N-terminal half of HGF alpha-chain is the principal heparin
      binding site. The hairpin loop in HGF possesses a cluster of basic amino acid
      residues and a highly positive net charge, when compared with hairpin loop
      structures in the other proteins, plasminogen and HGF-like protein. The second
      kringle domain in HGF has the basic amino acid cluster in the central region.
      Thus, it is likely that the basic clusters in these domains cooperatively
      contribute to the binding of HGF to the anionic heparin or heparan sulfate
      molecule.

PMID- 8288572
TI  - Characterization of rhoGAP. A GTPase-activating protein for rho-related small
      GTPases.
AB  - GTPase-activating proteins or GAPs play an important role in signal transduction
      pathways regulated by GTP-binding proteins. In addition to acting as down
      regulators of GTPases, there is growing evidence that they also act as effector
      molecules required for downstream signaling. PLC-beta 1, the target protein
      regulated by the heterotrimeric GTPase Gq, has been shown to be a GAP, whereas
      rasGAP, a down-regulator of the small GTPase ras, may be required for the ras
      mediated signals. We have purified a GAP specific for the rho subfamily of small
      GTPases. Partial sequence analysis of rhoGAP has led to the identification of a
      family of related proteins which now includes bcr, chimaerin, p190, p85, and 3BP
      1. We report here the isolation of a cDNA clone encoding human rhoGAP and the
      expression of recombinant protein. The full-length protein is 50 kDa and is
      ubiquitously expressed in mammalian cells. At least three members of the rho
      family are substrates for rhoGAP, rho, rac, and G25K/CDC42, and they each bind
      equally well to the protein. In vitro GTPase assays, however, reveal that
      G25K/CDC42 is the preferred substrate. RhoGAP contains a proline-rich sequence,
      suggesting that it is an SH3-binding protein.

PMID- 8288573
TI  - Growth factors differentially stimulate the phosphorylation of Shc proteins and
      their association with Grb2 in PC-12 pheochromocytoma cells.
AB  - Growth factor receptor tyrosine kinases can form stable associations with
      intracellular proteins that contain src homology (SH) 2 domains, including two
      proteins, Shc and Grb2, that are thought to lie upstream from the ras
      protooncogene in a signaling cascade. The phosphorylation and molecular
      associations of these proteins were evaluated in PC-12 pheochromocytoma cells
      treated with nerve growth factor (NGF), epidermal growth factor (EGF), and
      insulin. Both NGF and EGF stimulated the tyrosine phosphorylation of Shc proteins
      and their subsequent association with the receptors. In contrast, insulin had no
      effect on Shc phosphorylation, despite the expression of functional insulin
      receptors in these cells at levels comparable to those observed for NGF and EGF.
      NGF and EGF also induced the association of Shc proteins with a Grb2 fusion
      protein or endogenous Grb2, whereas insulin had no effect. All of the tyrosine
      phosphorylated Shc proteins associated with the Grb2 fusion protein, although
      only about half of the endogenous Shc was phosphorylated in response to NGF or
      EGF. However, all three hormones induced the association of several additional
      tyrosine phosphorylated proteins with Grb2, some of which also coprecipitated
      with antiserum against the 85-kDa subunit of phosphatidylinositol-3 kinase.
      Moreover, these growth factors stimulated the association of phosphatidylinositol
      3 kinase activity with the Grb2 fusion protein, although this activity was not
      detected in anti-Shc immunoprecipitates. These results provide further evidence
      for the divergence of signaling pathways in insulin action, and suggest that Grb2
      forms separate complexes with tyrosine-phosphorylated proteins in PC-12 cells.

PMID- 8288574
TI  - Specific binding of the peroxisomal protein targeting sequence to glyoxysomal
      membranes.
AB  - It has been demonstrated that the carboxyl-terminal amino acid sequence, serine
      lysine-leucine (SKL), is sufficient to direct a polypeptide to peroxisomes in
      vivo, and that this sequence is functional in plants, animals, and yeasts.
      Furthermore, many peroxisomal proteins have SKL carboxyl termini, including rat
      acyl-CoA oxidase. We have synthesized a 125I-peptide with the sequence of the
      last 12 amino acids of acyl-CoA oxidase, D-Tyr-HKHLKPLQSKL (SKLp), and used it to
      detect a receptor that recognizes SKL containing proteins targeted to
      glyoxysomes. SKLp binding to alkali-stripped glyoxysomal membranes was saturable
      and 80% of the binding could be displaced by 1 microM unlabeled SKLp or 8
      micrograms/ml glyoxysomal matrix proteins. Very little specific binding was
      associated with endoplasmic reticulum or mitochondrial membranes. Specific
      binding was affected by the ionic composition of the medium; the binding was
      optimal at pH 6.5 and was inhibited by mono- and divalent cations. Scatchard
      analysis of SKLp binding to glyoxysomal membranes indicated that there were two
      binding sites with Kd values of 160 and 1450 nM and abundances of 17 and 43
      nmol/mg glyoxysomal membrane protein, respectively. Protease treatment of the
      alkali-stripped glyoxysomal membranes lowered the number of high affinity sites
      and destroyed all the low affinity sites. These results demonstrate, for the
      first time, that there is an integral membrane protein in glyoxysomes that has
      the characteristics of a receptor for protein import.

PMID- 8288575
TI  - In vitro synthesis of the iron-molybdenum cofactor of nitrogenase. Purification
      and characterization of NifB cofactor, the product of NIFB protein.
AB  - The requirement of NIFB activity for the biosynthesis of iron-molybdenum cofactor
      (FeMo-co) can be satisfied by the addition of the low molecular weight product of
      NIFB, termed NifB cofactor (NifB-co). NifB-co has been purified to homogeneity by
      a unique one-step method. Addition of NifB-co into the FeMo-co synthesis system
      generated nitrogenase activity of 27-32 nmol of ethylene formed/min/nmol of iron.
      Iron is the only metal detected in the NifB-co. NifB-co-dependent in vitro FeMo
      co synthesis is absolutely dependent on the presence of molybdate, homocitrate
      and active NIFNE protein in the reaction mixture. The cofactor appears to be a
      small Fe-S cluster synthesized by NIFB, as a precursor of FeMo-co. NifB-co did
      not display any EPR signal at 4 K in 0-4000 gauss range. A solution of NifB-co is
      greenish-brown in color, similar to FeMo-co. NifB-co exhibits a broad absorbance
      between 400 and 700 nm with no distinctive peaks or shoulders. NifB-co is stable
      to repeated freeze-thaw cycles and is also stable in N-methylformamide, the
      solvent used for the isolation of FeMo-co. The NifB-co is stable to a 5-min heat
      treatment at 60 degrees C. The cofactor is extremely O2-labile, with half-life of
      less then 15 s in air.

PMID- 8288576
TI  - ATF-a0, a novel variant of the ATF/CREB transcription factor family, forms a
      dominant transcription inhibitor in ATF-a heterodimers.
AB  - We have isolated a cDNA encoding a variant of the transcription factor ATF-a
      (called ATF-a0) by screening a HeLa cDNA expression library with a regulatory
      element of the E-selectin promoter, NF-ELAM1/delta A. Relative to full-length ATF
      a, the ATF-a0 cDNA contains a large in-frame deletion of 525 base pairs that
      removes the P/S/T-rich putative transactivation domain. Using reverse
      transcription-polymerase chain reaction and Northern blot hybridization to
      characterize ATF-a0 expression, we found that putative mRNAs for ATF-a0 and ATF-a
      are present at varying ratios in different tissues. Full-length ATF-a is a
      transcriptional activator for the NF-ELAM1/delta A site of the E-selectin
      promoter. In contrast, we show ATF-a0 has no measurable transactivating function
      on this element. Moreover, we demonstrate that co-expressed ATP-a0 and ATF-a
      preferentially heterodimerize. In the heterodimer ATF-a0 is a dominant inhibitor
      that completely blocks the transactivating activity of ATF-a. Both forms of ATF-a
      bind the p50 subunit of NF-kappa B as shown by affinity chromatography. ATF-a0
      appears to be a splice variant similar to the one found for ATF-2, its closest
      homologue in structure and function. Taken together, our results suggest that ATF
      a0 is an important member of the ATF family with a negative regulatory role in
      transactivation.

PMID- 8288577
TI  - A novel gene, STT4, encodes a phosphatidylinositol 4-kinase in the PKC1 protein
      kinase pathway of Saccharomyces cerevisiae.
AB  - A staurosporine-sensitive mutation (stt1) in yeast has been found in the PKC1
      gene that encodes a protein kinase C homologue (Yoshida, S., Ikeda, E., Uno, I.,
      and Mitsuzawa, H. (1992) Mol. Gen. Genet. 231, 337-344). We report here another
      staurosporine-sensitive mutant, stt4, which shows very similar phenotypes to that
      of the stt1 mutant. The stt4 temperature-sensitive mutant arrests mostly in G2/M
      phase at 37 degrees C, and the stt4 deletion mutant shows an osmoremedial
      phenotype. Staurosporine sensitivity of the stt4 mutant was suppressed by
      overexpression of PKC1/STT1, indicating genetic interaction between stt4 and
      pkc1/stt1. The nucleotide sequence of STT4 predicts a hydrophilic protein
      composed of 1,900 amino acid residues, with 26% sequence identity to the yeast
      VPS34 gene product and 27% to the catalytic subunit of mammalian
      phosphatidylinositol (PI) 3-kinase, respectively. Cell homogenates of the stt4
      deletion mutant show normal PI3-kinase activity but lack most of the PI4-kinase
      activity that is detected in the wild-type. We conclude that STT4 encodes a yeast
      PI4-kinase that functions in the PKC1 protein kinase pathway.

PMID- 8288578
TI  - Growth state- and cell cycle-dependent fluctuation in the expression of two forms
      of DNA topoisomerase II and possible specific modification of the higher
      molecular weight form in the M phase.
AB  - The fluctuations in the expression of two forms of DNA topoisomerase II, p170 and
      p180, were examined by immunoblotting during the transition of the growth state
      and the cell cycle in Swiss 3T3 cells. The level of p170 expression was higher
      during the exponentially growing phase than in the stationary phase, and the
      level of p180 did not appear to change when the cells changed the growth state.
      When quiescent cells were stimulated with serum, the p170 level began to increase
      at 12 h and reached a maximal level at 24-28 h, corresponding to the G2 phase. In
      contrast, the level of p180 was almost constant during the cell cycle, and the
      p180 band became obscure when the number of mitotic cells increased.
      Immunoblotting of the samples prepared from metaphase-synchronized HeLa cells did
      not have a p180 band, but did exhibit a band with a higher molecular weight. This
      band increased and p180 decreased in parallel with the increase in the number of
      mitotic cells. When the cells exited from the M phase, p180 reappeared and the
      higher molecular weight band disappeared.

PMID- 8288579
TI  - The transcription factor HNF1 acts with C/EBP alpha to synergistically activate
      the human albumin promoter through a novel domain.
AB  - HNF1 and C/EBP alpha are transcription factors that bind to and trans-activate
      the human albumin gene proximal promoter. Various 5' deletions of the human
      albumin promoter were coupled to a luciferase reporter gene (alb-luc constructs)
      and co-electroporated with HNF1 and/or C/EBP alpha expression vectors into HeLa
      cells. Luciferase activities from co-electroporation of the HNF1 and C/EBP alpha
      expression vectors with the alb-luc constructs were approximately 10-fold greater
      than the sum of the activities achieved with HNF1 and C/EBP alpha alone. Analysis
      of COOH-terminal or internal deletions of the HNF1 expression vector revealed
      that the domain important for collaborative interaction with C/EBP alpha could be
      localized to a 157 amino acid region not previously described. This domain is
      proline and glutamine-rich and is highly homologous (66%) to a portion of vHNF1,
      an evolutionarily related gene first identified in dedifferentiated hepatoma
      cells. A construct linking the negatively charged activation domain of herpes
      simplex virus protein VP16 to the DNA-binding domain of HNF1 showed that it could
      also synergize with C/EBP alpha to trans-activate the human albumin gene
      promoter. Our studies delineate a domain in HNF1 important for synergistic
      activation with C/EBP alpha.

PMID- 8288580
TI  - The mouse osteocalcin gene cluster contains three genes with two separate spatial
      and temporal patterns of expression.
AB  - Osteocalcin is the most abundant noncollagenous protein of bone. Here we report
      that the mouse genome contains an osteocalcin cluster composed of three genes
      arranged within a 23-kilobase span of genomic DNA. We named them osteocalcin gene
      1 (OG1), osteocalcin gene 2 (OG2), and osteocalcin-related gene (ORG) in order
      from the 5' end to the 3' end of the cluster. Hybridization of polymerase chain
      reaction-amplified cDNAs with specific oligonucleotides and RNase protection
      assays showed that OG1 and OG2 are expressed only in bone, whereas ORG is
      transcribed in kidney but not in bone. Furthermore, during embryogenesis, OG1 and
      OG2 begin to be expressed at day 15.5, while ORG is transcribed as early as day
      10.5. The protein encoded by ORG has a similar pattern of expression and
      identical structural features to nephrocalcin, a calcium-binding protein
      partially purified from kidney that plays a role in calcium reabsorption and in
      prevention of nephrolithiasis. The nephrocalcin gene has not been cloned in any
      species; we propose that ORG is the mouse nephrocalcin gene. The existence of
      several osteocalcin or osteocalcin-related sequences is not restricted to mouse
      but is present in every species we examined.

PMID- 8288581
TI  - The calf 5'- to 3'-exonuclease is also an endonuclease with both activities
      dependent on primers annealed upstream of the point of cleavage.
AB  - The catalytic activity of the calf thymus 5'- to 3'-exonuclease was measured on
      substrates consisting of two primers annealed adjacent to each other on a
      template. Exonucleolytic degradation of the downstream primer is very slow if the
      primers are separated by a gap of one nucleotide or if no upstream primer is
      present. When only a nick separates the primers, degradation is rapid. This
      suggests that the nuclease is designed to work with calf DNA polymerases such
      that synthesis from an upstream primer creates the favored nuclease substrate.
      Nuclease action then destroys the substrate, but it is regenerated by further
      polymerization. This process, termed nick translation, is necessary for both DNA
      replication and repair. If the downstream primer has an unannealed 5'-region,
      that region is removed by an endonuclease activity residing in the same enzyme.
      Efficient endonuclease action also requires an upstream primer that is annealed
      such that its 3'-end is directly adjacent to the annealed region of the
      downstream primer. This reaction is likely to be important for removal of DNA
      segments that are damaged such that exonuclease cleavage of the damaged site is
      not possible.

PMID- 8288582
TI  - Transcription and editing of cytochrome oxidase II RNAs in Trypanosoma cruzi.
AB  - The cytochrome oxidase subunit II (COII) gene is one of the maxicircle
      cryptogenes of kinetoplastids whose primary transcripts are sometimes modified by
      RNA editing to produce mature mRNAs. We determined the sequence of the COII gene
      in three strains of Trypanosoma cruzi (Y, Corpus Christi, and Tulahuen) and
      examined its developmental expression. Comparison of the RNA and DNA sequences
      encoding COII indicated that in the three strains of T. cruzi, four uridines are
      inserted in the pre-mRNA at the same positions as they are in the COII pre-mRNAs
      of Trypanosoma brucei, Leishmania tarentolae, and Crithidia fasciculata. The
      putative guide RNA (gRNA) sequence that serves as a template for the four uridine
      insertions is located in the 3'-untranslated region of the T. cruzi COII mRNA.
      Analysis of editing intermediates demonstrates that the COII gRNA remains
      attached to the pre-mRNA while participating in the formation of chimeric RNAs.
      Northern blots used to investigate stage-specific expression of the COII gene
      revealed RNAs of 800 and 900 nucleotides, similar in size to those present in T.
      brucei. In contrast to the differential expression observed in T. brucei, no
      difference occurs between the COII mRNA levels of insect and mammalian stages of
      T. cruzi.

PMID- 8288583
TI  - The active site of hamster 3-hydroxy-3-methylglutaryl-CoA reductase resides at
      the subunit interface and incorporates catalytically essential acidic residues
      from separate polypeptides.
AB  - We employed site-directed mutagenesis based on sequence comparisons and
      characterization of purified mutant enzymes to identify Glu558 and Asp766 of
      Syrian hamster 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC
      1.1.1.34) as essential for catalysis. Mutant enzymes E558D, E558Q, and D766N had
      wild-type Km values for (S)-HMG-CoA and NADPH, but exhibited less than 0.5% of
      the wild-type catalytic activity. The inactive mutant polypeptides E558Q and
      D766N nevertheless can associate to generate an active enzyme. In vitro, 6% of
      the wild-type activity was observed when mutant polypeptides E558D and D766N were
      mixed in the absence of chaotropic agents. When mutant polypeptides E558Q and
      D766N were co-expressed in Escherichia coli, the resulting purified enzyme had
      25% of wild-type activity. Hamster HMG-CoA reductase thus is a two-site, dimeric
      enzyme whose subunits associate to form an active site in which each monomer
      contributes at least one residue (e.g. Glu558 from one monomer and Asp766 from
      the other). The wild-type enzyme behaves as a dimer during size exclusion
      chromatography and has one HMG-CoA binding site per monomer. Syrian hamster HMG
      CoA reductase thus appears to be a homodimer with two active sites which are
      located at the subunit interface.

PMID- 8288584
TI  - Primary structure, ligand binding, and localization of the human type 3 inositol
      1,4,5-trisphosphate receptor expressed in intestinal epithelium.
AB  - The second messenger, inositol 1,4,5-trisphosphate (InsP3) transduces many
      hormonal signals which regulate Ca(2+)-dependent processes in the intestinal
      epithelium. To study the receptors for InsP3 (InsP3Rs), which function as
      intracellular Ca2+ channels, cDNA clones encoding InsP3Rs were isolated from a
      human colon adenocarcinoma cell line, HT29. The majority of clones encoded the
      type 3 InsP3R, the product of the ITPR3 gene on chromosome 6, for which only a
      147-amino-acid fragment was known previously (Ozcelik, T., Sudhof, T. C., and
      Francke, U. (1991) Cytogenet. Cell Genet. Abstr. 58, 1880; Sudhof, T. C., Newton,
      C. L., Archer, B. T., III, Ushkaryov, Y. A., and Mignery, G. A. (1991) EMBO J.
      10, 3199-3206). The complete sequence of the type 3 InsP3R polypeptide (2,671
      amino acids) is described here. Primary structure analysis indicates a pattern of
      conserved and variable regions which is characteristic of the InsP3R family. A
      250-kDa protein (SDS-PAGE) which specifically binds InsP3 is immunoprecipitated
      by affinity-purified antibodies raised against a COOH-terminal fusion protein.
      Transient expression in COS-7 cells of a polypeptide comprising the NH2-terminal
      750 amino acids establishes that the ligand-binding domain is localized to this
      region. Lysates from transfected COS-7 cells bind InsP3 with high affinity (Kd =
      151 nM) compared with other inositol phosphates (InsP3 >> Ins 1,3,4,5-P4 > InsP6
      > Ins 1,4-P2 >> Ins 1-P). Immunocytochemical localization in the intestine
      reveals expression in crypt and villus epithelial cells, but not in cells of the
      lamina propria, submucosa, or muscularis layers. The subcellular distribution and
      appearance of staining is consistent with localization on the endoplasmic
      reticulum, with the highest concentration of staining occurring adjacent to the
      apical brush border of villus cells.

PMID- 8288585
TI  - Molecular characterization of a new metabotropic glutamate receptor mGluR7
      coupled to inhibitory cyclic AMP signal transduction.
AB  - A cDNA clone for a new rat metabotropic glutamate receptor termed mGluR7 was
      isolated through polymerase chain reaction-mediated DNA amplification by using
      primer sequences conserved among the metabotropic receptor (mGluR) family and by
      the subsequent screening of a rat forebrain cDNA library. The cloned mGluR7
      subtype consists of 915 amino acid residues and exhibits a structural
      architecture common to the mGluR family with a large extracellular domain
      preceding the seven putative membrane-spanning domains. mGluR7 shows the highest
      sequence similarity to mGluR4 and mGluR6 among the members of the mGluR family.
      Similar to mGluR4 and mGluR6, mGluR7 inhibits forskolin-stimulated cyclic AMP
      accumulation in response to agonist interaction and potently reacts with L-2
      amino-4-phosphonobutyrate and L-serine-O-phosphate in Chinese hamster ovary cells
      transfected with the cloned cDNA. RNA blot and in situ hybridization analyses of
      mGluR7 mRNA indicated that it is widely expressed in many neuronal cells of the
      central nervous system and is thus different from the more limitedly expressed
      mGluR4 or mGluR6 mRNA. mGluR7 together with mGluR4 thus corresponds to the
      putative L-2-amino-4-phosphonobutyrate receptor which plays an important role in
      modulation of glutamate transmission in the central nervous system.

PMID- 8288586
TI  - Transport of an export-defective protein by a highly hydrophobic signal peptide.
AB  - We have examined the sequence constraints on the amino-terminal region of the
      mature portion of alkaline phosphatase that are important for its efficient
      transport in Escherichia coli. Using a homopolymeric sequence of serines to
      replace 6 residues in this region, a transport-incompetent mutant was produced.
      Reintroduction of residues from the native sequence which restore charge and beta
      turn potential resulted in little improvement. However, by replacing the
      hydrophobic core of the signal peptide with a homopolymeric series of leucines,
      not only was transport restored but precursor processing was more efficient than
      for the wild type and was insensitive to disruption of the protonmotive force.
      Moreover, we have titrated the signal peptide with leucine to alanine
      substitutions (Doud, S. K., Chou, M. M., and Kendall, D. A. (1993) Biochemistry
      32, 1251-1256) and determined the minimum level of hydrophobicity necessary to
      achieve transport of the mutant protein. The results indicate that signal peptide
      hydrophobicity can completely override possible requirements for negatively
      charged residues and strong beta-turn forming potential in the mature protein and
      that the polyleucine-containing signal peptide may act as a generic signal
      sequence for the transport of non-native proteins in E. coli.

PMID- 8288587
TI  - Protein kinase C-mediated serine phosphorylation directly activates Raf-1 in
      murine hematopoietic cells.
AB  - We have previously found that Raf-1, which is activated by hematopoietic growth
      factors in association with phosphorylation, is required for hematopoietic cell
      proliferation. Recently, 12-O-tetradecanoylphorbol 13-acetate has been found to
      mediate Raf-1 phosphorylation, suggesting that protein kinase C (PKC) may be
      involved in the Raf-1 activation mechanism(s). Since PKC can be activated by
      hematopoietic growth factors, it was investigated as a potential "Raf-1 kinase
      kinase." Results demonstrate that bryostatin 1, a pharmacologic activator of PKC,
      induces activation of Raf-1 in FDC-P1 cells. PKC inhibitors H7 and staurosporine
      block both bryostatin 1- and interleukin-3-mediated Raf-1 phosphorylation and FDC
      P1 cell proliferation. Additionally, an antisense c-raf oligodeoxyribonucleotide
      specifically inhibits bryostatin 1-mediated proliferation, indicating a necessary
      role for Raf-1 in PKC signaling. Purified PKC can phosphorylate Raf-1 serine
      residues to high stoichiometry in vitro. Comparative phosphopeptide maps localize
      two PKC phosphorylation sites to Raf-1 phosphopeptides isolated from
      hematopoietic growth factor- or bryostatin 1-stimulated cells. The sites of PKC
      mediated Raf-1 phosphorylation are deduced to be Ser497 and Ser619. Furthermore,
      PKC-mediated serine phosphorylation is sufficient to activate the enzymatic
      function of Raf-1 in vitro. These findings demonstrate that activated PKC can
      promote hematopoietic cell growth by regulating the enzymatic activity of Raf-1
      through direct serine phosphorylation.

PMID- 8288588
TI  - Thrombospondin 3 is a developmentally regulated heparin binding protein.
AB  - The thrombospondins (TSPs) are a growing family of cell surface and extracellular
      matrix molecules composed of multiple repeating elements. Thrombospondin 3 is a
      recently described member that possesses the calcium binding Type 3 repeats, has
      4 epidermal growth factor receptor-like Type 2 repeats, a complete absence of the
      complement-like Type 1 repeats, and a distinct N terminus that has no significant
      homology to the other TSPs. Metabolic labeling and immunoprecipitation analysis
      of cells transfected with a TSP3 expression vector revealed it to be an
      oligomeric heparin binding protein present in both the cell layer and medium.
      Finally, a combination of in situ hybridization and immunocytochemistry
      demonstrated TSP3 to be expressed in a temporal and spatial manner during murine
      embryogenesis, especially in the gut, cartilage, lung, and central nervous
      system.

PMID- 8288589
TI  - Deletion of QCR6, the gene encoding subunit six of the mitochondrial cytochrome
      bc1 complex, blocks maturation of cytochrome c1, and causes temperature-sensitive
      petite growth in Saccharomyces cerevisiae.
AB  - It was previously reported that disruption or deletion of QCR6, the nuclear gene
      encoding subunit 6 of the cytochrome bc1 complex, does not impair growth of yeast
      on non-fermentable carbon sources (Schoppink, P. J., Hemrika, W., Reyne, J. M.,
      Grivell, L.A., and Berden, J. A. (1988) Eur. J. Biochem. 113, 115-122;
      Crivellone, M. D., Wu, M. M., and Tzagoloff, A. (1988) J. Biol. Chem. 262, 14323
      14333; Schmitt, M. E., and Trumpower, B. L. (1990) J. Biol. Chem. 265, 17005
      17011). We have discovered that deletion of QCR6 results in a temperature
      sensitive petite phenotype, manifested at 37 degrees C, and that this phenotype
      can be masked by spontaneously arising suppressor mutations. Mitochondrial
      membranes from the deletion strain grown at 37 degrees C lack ubiquinol
      cytochrome c reductase activity, and optical spectra reveal an extensive decrease
      in cytochrome b absorption, but little or no decrease in cytochrome c1
      absorption. Immunoblots of mitochondrial membrane proteins from the deletion
      strain indicate that processing of cytochrome c1 from intermediate to mature size
      is blocked coincident with the loss of subunit 6. This is the first example where
      mutation of a subunit within the bc1 complex blocks maturation of cytochrome c1.

PMID- 8288590
TI  - Suppressed collagen gene expression and induction of alpha 2 beta 1 integrin-type
      collagen receptor in tumorigenic derivatives of human osteogenic sarcoma (HOS)
      cell line.
AB  - Cell-matrix interactions and intergrin-type cell adhesion receptors are involved
      in the regulation of tumor cell invasion and metastasis. We have analyzed the
      expression of matrix proteins and their cellular receptors in human osteosarcoma
      cells (HOS) and in their virally (KHOS-NP) and chemically (HOS-MNNG) transformed
      tumorigenic subclones. Transformation decreased dramatically the cellular mRNA
      levels of alpha 1(I) collagen. Concomitantly with down-regulation of collagen
      mRNA levels the synthesis of the collagen receptor, alpha 2 beta 1 integrin, was
      induced. No alpha 2 integrin mRNA was found in HOS cells, suggesting that its
      expression was regulated most probably at the transcriptional level. 5
      Azacytidine alone or combined with alpha 2 integrin-stimulating cytokines,
      transforming growth factor-beta 1, and interleukin-1 beta, did not turn on the
      alpha 2 integrin gene. In chemically transformed cells, however, alpha 2 integrin
      expression could be regulated by cytokines. Thus, we suggest that HOS cells have
      a strong element, probably other than cell culture-generated de novo promoter
      methylation, suppressing alpha 2 integrin expression and that this factor is lost
      in both chemical and viral transformation. Furthermore, the mechanism used by
      cytokines and malignant transformation to increase alpha 2 integrin expression
      seems not to be identical. Other transformation-related changes in beta 1
      integrins were (i) reduction of the intracellular pool of precursor beta 1 (in
      HOS-MNNG cells), leading to faster maturation rate of beta 1 subunit and slower
      maturation rate of alpha subunits, and (ii) decreased electrophoretic mobility of
      both alpha and beta 1 subunits. At the cellular level both chemical and viral
      transformation increased cell adhesion to type I collagen.

PMID- 8288591
TI  - The purification and characterization of gene 59 protein from bacteriophage T4.
AB  - Gene 59 of bacteriophage T4 is involved in genetic recombination and
      recombination-dependent DNA replication. We purified the protein encoded by gene
      59 after cloning the gene in an expression vector. The molecular weight and the
      sequence of seven N-terminal amino acids of the protein were consistent with the
      nucleotide sequence of the gene (Hahn, S., Kruse, U., and Ruger, W. (1986)
      Nucleic Acids Res. 14, 9311-9327). The purified 59 protein appeared to be a
      monomer under nondenaturing conditions, and it bound to single-stranded DNA in
      preference to double-stranded DNA. The protein could bind to a 24-nucleotide-long
      single-stranded DNA molecule that had previously bound either 32 protein (single
      stranded DNA-binding protein) or uvsY protein (enhancer of uvsX protein), but it
      would not bind to this DNA if it had previously bound uvsX protein (synaptase).
      The binding occurred rapidly with 32 protein-bound DNA and slowly with uvsY
      protein-bound DNA. Accordingly, 32 protein bound specifically to an agarose
      matrix containing immobilized 59 protein. The 41 protein (DNA helicase) also
      bound specifically to this agarose matrix.

PMID- 8288592
TI  - Pituitary adenylate cyclase activating polypeptide is an extraordinarily potent
      intra-pancreatic regulator of insulin secretion from islet beta-cells.
AB  - Insulin secretion from pancreatic islets is controlled by peptides as well as by
      nutrients. We report here a novel, extraordinarily potent peptidergic regulation
      of insulin secretion. A 27-residue form of pituitary adenylate cyclase activating
      polypeptide (PACAP27) as low as 10(-14) to 10(-13) M stimulated insulin release
      from rat islets in a glucose-dependent manner. PACAP27 also increased cytosolic
      free Ca2+ concentration ([Ca2+]i) in islet beta-cells. Nitrendipine, a blocker of
      the L-type Ca2+ channel, abolished both [Ca2+]i and insulin responses. Vasoactive
      intestinal peptide, a peptide exhibiting 68% amino acid homology with PACAP, also
      increased [Ca2+]i in beta-cells but only at concentrations in the nanomolar
      range, indicating that PACAP27 is 4 logs more potent. A 38-residue form of the
      peptide (PACAP38) stimulated insulin release and increased beta-cell [Ca2+]i in a
      manner similar to that of PACAP27. PACAP-like immunoreactivity was demonstrated
      in pancreatic nerve fibers, islets, and capillaries. The results indicate that
      PACAP is a physiologically occurring peptide in pancreas and that PACAP, in a
      glucose-dependent manner, activates beta-cells presumably via a high affinity
      PACAP-selective receptor, raises [Ca2+]i by increasing the activity of L-type
      Ca2+ channels, and consequently stimulates insulin release. PACAP appears to be
      by far the most potent insulinotropic peptide known.

PMID- 8288593
TI  - Purple acid phosphatase of the human macrophage and osteoclast. Characterization,
      molecular properties, and crystallization of the recombinant di-iron-oxo protein
      secreted by baculovirus-infected insect cells.
AB  - The purple phosphatases catalyze hydrolysis of phosphate esters (optimum pH
      approximately 5) and are resistant to inhibition by dextro-rotatory tartrate;
      their distinctive color is due to Fe(III)-phenolate charge-transfer transitions
      at their active site. Expression of human purple phosphatase, designated type 5
      acid phosphatase, is restricted to osteoclasts and other activated cells of
      monohistiocytic lineage, but its biological role in relation to bone resorption
      and phagocytosis is unknown. To characterize this enzyme further, we have
      engineered the human type 5 acid phosphatase into a baculovirus vector expression
      system that enabled milligram quantities of purple protein to be purified from
      medium containing Sf9 host cells. The phosphatase cDNA was transcribed as a
      single RNA species of 1.5 kilobases as in human tissues. Tartrate-resistant acid
      phosphatase activity reacting with uteroferrin antisera appeared in the culture
      medium, from which up to 8 mg/liter was purified by two-step cation-exchange
      chromatography at pH 8.0. Two isoforms of approximately 36 kDa were identified by
      SDS-polyacrylamide electrophoresis and were converted to a single species of
      apparent molecular size 34 kDa upon treatment with N-glycosidase F, indicating
      secreted glycoforms of a single polypeptide. Mass spectroscopy showed that the
      mean molecular mass of the active, secreted glycoprotein was 35849 Da. The
      recombinant enzyme (specific activity, 190 mumol p-nitrophenol/min/mg at 37
      degrees C) contained 2 iron atoms/molecule and formed purple, monoclinic
      crystals. Exposure to the ferric chelator, 1,2-dimethyl-3-hydroxypyrid-4-one,
      rapidly inactivated the enzyme, which was not inhibited by alpha, alpha'
      bipyridyl, a ferrous chelator. That ferric iron is essential for enzymatic
      catalysis, was further indicated by the synergistic effects of the reductant,
      dithiothreitol, and bipyridyl on phosphatase activity. The recombinant purple
      phosphatase catalyzed the peroxidation of 5-aminophthalhydrazide (luminol), as
      evidenced by the induction of chemiluminescence; this reaction was inhibited by
      alpha, alpha'-bipyridyl at concentrations that did not inhibit phosphatase
      activity. The divalent iron moiety of human type 5 phosphatase may therefore
      participate in the generation of free radical species by fluid-phase reactions
      involving Fenton chemistry that are dissociated from its phosphatase function.

PMID- 8288594
TI  - Identification of basic amino acid residues in thrombin essential for heparin
      catalyzed inactivation by antithrombin III.
AB  - The therapeutically important anticoagulant heparin catalyzes inactivation of
      thrombin by antithrombin III via formation of an intermediary ternary thrombin
      heparin-antithrombin III complex that is subsequently converted to a stable
      thrombin-antithrombin III complex with the release of heparin. Point mutations at
      Arg-180, Arg-245, Lys-248, and Lys-252 in thrombin markedly reduced the
      efficiency of heparin catalysis by decreasing the stability of the ternary
      intermediate, whereas the inactivation of thrombin by antithrombin alone was not
      affected by these mutations. These results together with an analysis of the x-ray
      crystal structure of thrombin yielded a model for the thrombin-heparin
      interaction, wherein heparin forms salt linkages along a groove in thrombin
      defined by Lys-252, Lys-248, Arg-245, Arg-89, Arg-98, and Arg-180.

PMID- 8288595
TI  - G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine
      kinase gene promoter.
AB  - By performing DNase I footprint analysis, we had identified three distinct
      protein binding sequences (MT1, MT2, and MT3) located on the mouse thymidine
      kinase (TK) upstream promoter (Dou, Q.-P., Fridovich-Keil, J. L., and Pardee,
      A.B. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1157-1161). Here we report that MT2
      includes an E2F-like binding site (GTTCGCGGGCAAA), as shown by the following
      evidence. (i) MT2 bound specifically to an affinity-purified fusion human E2F
      protein. (ii) Both MT2 and an authentic E2F site (TTTCGCGCGCTTT) bound
      specifically to similar or identical nuclear protein complexes. (iii) Formation
      of both these DNA-protein complexes were cell cycle-dependent: a G0/G1 phase
      specific complex (E2F.G0/G1) was replaced by an S phase-specific complex(es)
      (E2F.S), whereas "free" E2F increased after the G1/S transition. (iv) Pulse
      inhibition of protein synthesis with cycloheximide interchanged these complexes
      with similar kinetics. (v) When MT2-shifted E2F.G0/G1, E2F.S, and free E2F were
      eluted and analyzed by Western blot assay using a specific antiserum to human E2F
      1, two forms of murine E2F (62 and 66 kDa) were observed from all three
      complexes. The compositions of these MT2-bound complexes were also investigated.
      Studies using specific antibodies revealed that p107, a retinoblastoma-like
      protein, was present in both E2F-G0/G1 and E2F.S, whereas cyclin E.cyclin A.cdk2
      were only present in E2F.S complex(es). These data suggest that removal of the
      p107-containing E2F.G0/G1 complex, a candidate repressor, from the MT2 site in
      late G1 may be essential for S phase-dependent transcription of the mouse TK
      gene.

PMID- 8288596
TI  - In vitro transcriptional studies of the roles of the thyroid hormone (T3)
      response elements and minimal promoters in T3-stimulated gene transcription.
AB  - Thyroid hormone receptors (TRs) are ligand-dependent nuclear transcription
      factors that are encoded by two different genes, TR alpha and TR beta, and bind
      to thyroid hormone response elements (TREs) in the promoters of thyroid hormone
      (T3)-regulated genes. Retinoid X receptors (RXRs), major members of the thyroid
      hormone receptor auxiliary proteins, have recently been shown to enhance the
      binding of TRs to TREs. We previously showed that TRs extracted from rat
      pituitary GH3 cells retain ligand (T3) and DNA binding specificity and stimulate
      rat growth hormone (rGH) promoter activity in a cell-free in vitro transcription
      system. In this report, we have studied further how T3 activates endogenous TRs
      and stimulates transcription from different TRE-containing promoters. We found
      that T3 (10(-8) M) selectively stimulates transcription from rGH-TRE- and TREpal
      , but not ME-TRE- and F2-TRE-, containing templates in which these TREs are
      linked in front of the rGH minimal promoter containing only the TATA box binding
      protein, but not any other proximal binding protein, sequence. In contrast, only
      the TREpal/AdML template, in which TREpal oligonucleotide was linked in front of
      the adenovirus major late gene (AdML) minimal promoter, was stimulated by T3.
      Electrophoretic mobility shift assay (EMSA) demonstrates that endogenous TR
      complexes specifically bind to either natural or idealized TRE (rGH-TRE, TREpal,
      ME-TRE, and F2-TRE) oligonucleotides. To further understand these receptor-DNA
      complexes formed on various TREs, isoform-specific anti-receptor antisera (TR
      alpha, TR beta 1, TR beta 2, and RXR beta) were added in the EMSA. These antisera
      differentially supershifted TR.DNA complexes formed on the TREs. These data
      suggest either that endogenous TR isoforms and RXR beta may form different
      complexes on the various TREs or that TR.RXR complexes have distinct
      conformations when bound to the various TREs. Taken together, these data suggest
      that particular TREs in which specific TR.RXR complexes are formed and different
      minimal promoters may provide specificity in T3-mediated transcriptional
      stimulation of gene expression.

PMID- 8288597
TI  - Determination of tissue specificity of the enhancer by combinatorial operation of
      tissue-enriched transcription factors. Both HNF-4 and C/EBP beta are required for
      liver-specific activity of the ornithine transcarbamylase enhancer.
AB  - The enhancer of the rat ornithine transcarbamylase gene is located 11 kilobases
      upstream from the transcription start site and has been shown to be hepatoma cell
      specific. Using transgenic mice, we showed that this enhancer is capable of
      activating transcription in a liver-specific manner, inverting the tissue
      specificity of the homologous promoter that is by itself more active in the small
      intestine than in the liver. Transient transfection analysis with cultured
      hepatoma cells indicated that the enhancer activity resides in the approximately
      110-base pair region containing four protein-binding sites, two for hepatocyte
      nuclear factor-4 (HNF-4) and two for CCAAT/enhancer binding protein (C/EBP), both
      of which are liver-selective transcription factors. Concatemerization of a region
      containing one HNF-4 and one C/EBP site led to reconstitution of the hepatoma
      cell-specific enhancer, and intactness of these two sites was strictly required
      for the enhancer activity. Furthermore, cotransfection experiments showed that
      both HNF-4 and C/EBP beta are necessary, and neither alone sufficient, for
      activation of the reconstituted enhancer in nonhepatic cells. Requirement of
      combinatorial operation of at least two liver-enriched transcription factors for
      transcriptional activation successfully explains why these liver-selective but
      not strictly liver-specific factors can confer more restricted liver specificity
      on transcription of their target genes.

PMID- 8288598
TI  - Biochemical and assembly properties of GluR6 and KA2, two members of the kainate
      receptor family, determined with subunit-specific antibodies.
AB  - To examine subunit assembly and biochemical properties of two members of the
      kainate family of glutamate receptors (GluR), antibodies were made to synthetic
      peptides corresponding to the carboxyl termini of GluR6 and KA2. Immunoblot
      analysis of membranes from human embryonic kidney cells transfected with
      glutamate receptor cDNAs showed that these antibodies are selective for their
      respective receptor subunit except that the antibody to GluR6 also recognizes
      GluR7, which is expected due to the sequence homology between the two subunits at
      the carboxyl terminus. In transfected cell membranes, immunoblot analysis with
      the antibody to GluR6 showed a major immunoreactive band at 118 kDa and minor
      bands at 103 and 28 kDa. The 103-kDa band appears to be a deglycosylated form of
      GluR6 since deglycosylation eliminates staining at 118 kDa and increases staining
      of the 103-kDa band. Immunoblot analysis of KA2 transfected cell membranes shows
      a major band at 123 kDa and minor bands at 109 and 37 kDa. Deglycosylation
      converts the 123-kDa band into a 109-kDa band. Analysis of brain tissues shows
      that both antibodies label single major bands which migrate at the same molecular
      masses as those from transfected cell membranes, 118 and 123 kDa for GluR6 and
      KA2, respectively. Immunoprecipitation studies showed that antibodies to GluR6
      and KA2 selectively immunoprecipitated [3H]kainate binding activity, but not 3H
      labeled alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) binding
      activity, from Triton X-100-solubilized rat brain membranes. Furthermore, each
      antibody coimmunoprecipitated GluR6 and KA2 from cells co-transfected with GluR6
      and KA2 cDNAs and from detergent-solubilized rat brain membranes, indicating that
      these two subunits can coassemble into a molecular complex. Interestingly, GluR1
      and GluR2, subunits of the AMPA receptor, also co-immunoprecipitated with GluR6
      in cells co-transfected with GluR6 and GluR1 or GluR2 cD-NAs. Such complexes
      appear to be present to a limited extent in the brain.

PMID- 8288599
TI  - Expression cloning and characterization of the hamster ileal sodium-dependent
      bile acid transporter.
AB  - Active uptake of bile acids from the lumen of the small intestine is mediated by
      an ileal Na(+)-dependent bile acid transport system. To identify components of
      this transport system, an expression cloning strategy was employed to isolate a
      hamster ileal cDNA that exhibits bile acid transport activity. By Northern blot
      analysis, mRNA for the cloned transporter was readily detected in ileum and
      kidney but was absent from liver and proximal small intestine. The transporter
      cDNA encoded a 348-amino acid protein with seven potential transmembrane domains
      and three possible N-linked glycosylation sites. The amino acid sequence was 35%
      identical and 63% similar to the rat liver Na+/bile acid cotransporter. After
      transfection into COS cells, the hamster cDNA transported taurocholate in a
      strict Na(+)-dependent fashion with an apparent Km of 33 microM. This
      taurocholate transport was inhibited by various bile acids but not by taurine or
      other organic anions. The Na+ dependence, saturability, and bile acid specificity
      of transport as well as the tissue specificity of mRNA expression strongly argue
      that the transporter cDNA characterized in this study is the Na+/bile acid
      cotransporter described previously in ileum.

PMID- 8288600
TI  - Association of the regulatory beta-adrenergic receptor kinase with rat liver
      microsomal membranes.
AB  - beta-Adrenergic receptor kinase (beta ARK) is a regulatory enzyme involved in the
      modulation of beta-adrenergic and other G protein-coupled receptors. It has been
      described that beta ARK is a cytosolic protein that transiently translocates to
      the plasma membrane in order to specifically phosphorylate agonist-occupied
      receptors. In this report, we used beta ARK-specific antibodies to demonstrate
      that a significant amount of this kinase is present in rat liver microsomal
      membranes. beta ARK seems to be peripherally associated with the cytosolic side
      of microsomal membranes since it can be stripped from the membranes by mild salt
      treatment. Cell-free association experiments indicate that the interaction of
      beta ARK is reversible, saturable, and strongly inhibited by protease or heat
      treatment of the microsomes, thus suggesting that beta ARK interacts with a
      protein component of the microsomal membrane. Gradient fractionation studies
      indicate that the highest beta ARK-specific activity co-migrates with endoplasmic
      reticulum enzymatic markers. Furthermore, indirect immunofluorescence and
      immunogold electron microscopy experiments performed in cultured cells using
      affinity-purified anti-beta ARK antibodies are consistent with this subcellular
      localization pattern. Taken together, our data suggest that several beta ARK
      pools (i.e. microsome-bound, plasma membrane-bound, and cytosolic) may exist
      inside the cell. Such results are in line with recent reports showing that
      proteins involved in plasma membrane signal transduction, such as heterotrimeric
      G proteins, are also associated with membranes of different intracellular
      organelles.

PMID- 8288601
TI  - Cloning and expression of a cDNA for mouse prostaglandin F receptor.
AB  - A functional cDNA clone for mouse prostaglandin (PG) F receptor was isolated from
      a mouse cDNA library using polymerase chain reaction based on the sequence of
      cloned prostanoid receptors, and cross-hybridization screening. The mouse PGF
      receptor consists of 366 amino acid residues with putative seven transmembrane
      domains. The sequence revealed the highest homology to the EP1 subtype of PGE
      receptor and thromboxane (TX) A2 receptor. Ligand binding studies using membranes
      of COS cells transfected with the cDNA revealed specific [3H]PGF2 alpha binding.
      The binding was displaced with unlabeled PGs in the order of PGF2 alpha = 9
      alpha, 11 beta PGF2 > PGF 1 alpha > PGD2 > STA2 (a stable TXA2 agonist) > PGE2 >
      iloprost (a stable PGI2 agonist). PGF2 alpha increased inositol trisphosphate
      formation in a concentration-dependent manner in COS cells expressing PGF
      receptor. RNA blot and in situ hybridization analyses demonstrated that the PGF
      receptor transcripts are abundantly expressed in luteal cells of corpus luteum
      and in a lesser amount in kidney, heart, stomach, and lung.

PMID- 8288602
TI  - Lipopolysaccharide induction of tissue factor expression in THP-1 monocytic
      cells. Protein-DNA interactions with the promoter.
AB  - Tissue factor, the cellular receptor for factor VII/VIIa, activates both the
      intrinsic and extrinsic pathways of blood coagulation. In this analysis we have
      used DNase I footprinting to map the sites of protein-DNA interaction along the
      promoter (-383 to +8) using nuclear extracts prepared from uninduced and
      lipopolysaccharide-induced THP-1 cells. We have identified six regions that
      interact with nuclear factors in both uninduced and induced extracts. Four
      footprints are contained within a region reported to confer base-line high level
      expression and lipopolysaccharide and serum induction. Two additional footprints
      map to a region reported to reduce basal transcription by 50%. The only
      qualitative change in the footprint pattern with uninduced and induced extracts
      is the appearance of two hypersensitive sites with uninduced extracts. In
      addition, changes in the level of protein- DNA binding are detected with only one
      probe by DNA mobility shift analysis. A combination of well characterized
      transcription factors (AP1), primarily lymphoid cell specific regulatory proteins
      (NF-kappa B- and/or Ets-1-related proteins), as well as additional,
      uncharacterized proteins appear to interact with these sequences. Our data
      suggest that post-translational modification of existing transcription factors,
      and not induction of new DNA-binding activity, mediates the lipopolysaccharide
      induction of tissue factor synthesis in THP-1 cells.

PMID- 8288603
TI  - Horseshoe crab (1,3)-beta-D-glucan-sensitive coagulation factor G. A serine
      protease zymogen heterodimer with similarities to beta-glucan-binding proteins.
AB  - Horseshoe crab factor G is an intracellular serine protease zymogen that
      initiates the (1,3)-beta-D-glucan-sensitive hemolymph clotting pathway. Unlike
      other known serine protease zymogens, which are composed of a single subunit,
      factor G consists of two distinct subunits, alpha and beta, which are
      autocatalytically converted to active factor G in the presence of (1,3)-beta-D
      glucan. We have now cloned and sequenced cDNAs encoding both subunits of factor
      G. The subunits are derived from separate mRNA species and thus encoded by
      different genes. Subunit beta is a serine protease zymogen which consists of 278
      residues with a calculated molecular mass of 30,846 Da; it exhibits homology to
      the serine protease domain of horseshoe crab factor B. Subunit alpha, on the
      other hand, is a new type of mosaic protein with intriguing features. The mature
      protein consists of 654 residues with a calculated molecular mass of 73,916 Da.
      The NH2-terminal portion of this subunit is similar to bacterial beta-1,3
      glucanases. Its 126 amino acid COOH terminus exhibits a repetitive sequence
      having partial homology to xylanases. Between these regions are three repeating
      units of 47 amino acids, whose similarity to carbohydrate-binding proteins
      suggests that these may be the (1,3)-beta-D-glucan-binding domain(s) of factor G.
      Factor G, thus, is a structurally unique heterodimeric serine protease zymogen
      and as such may represent a new class of active defense proteins.

PMID- 8288604
TI  - Two lectins from the marine sponge Halichondria okadai. An N-acetyl-sugar
      specific lectin (HOL-I) and an N-acetyllactosamine-specific lectin (HOL-II).
AB  - Two lectins (HOL-I and HOL-II) were isolated from the marine sponge Halichondria
      okadai by affinity chromatography on a bovine submaxillary mucin (BSM)-Toyopearl
      and an acid-treated Sepharose 4B columns, respectively. In hemagglutination
      inhibition assays, GlcNAc, GalNAc, and their methyl glycosides were the most
      potent inhibitors among the monosaccharides tested against the HOL-I-mediated
      hemagglutination, suggesting that HOL-I can especially recognize the N-acetyl
      groups of the sugars. This N-acetyl specificity was supported by 1H NMR analyses;
      the highest field-shifts of the signal of the N-acetyl group among all the
      signals in Me beta GlcNAc were observed in 1H NMR spectra of mixtures of HOL-I
      and the sugar. Among the oligosaccharides tested, GlcNAc beta 1-->4(GlcNAc beta 1
      ->2)Man alpha 1-O(CH2)2 CH3 was the most potent inhibitor, and the inhibitory
      potency of the oligosaccharide was 2(4) times greater than those of GlcNAc and
      GalNAc. On the other hand, N-acetyllactosamine (Gal beta 1-->4GlcNAc) and its
      analogs were the strongest inhibitors toward HOL-II-induced hemagglutination. The
      agglutination was completely inert to Gal beta 1-->3GlcNAc, Gal beta 1-->6GlcNAc,
      Gal beta 1-->3GalNAc, Gal beta 1-->4GalNAc, and Gal beta 1-->6GalNAc.
      Furthermore, HOL-II exhibited no binding ability to BSM, asialo-BSM, fetuin,
      asialofetuin, alpha 1-acid glycoprotein, and human transferrin. These results
      indicate that HOL-II strictly recognizes simple Gal beta 1-->4GlcNAc unit.

PMID- 8288605
TI  - Identification of discrete structural domains in the retinoblastoma protein.
      Amino-terminal domain is required for its oligomerization.
AB  - To characterize the protein product of the retinoblastoma tumor suppressor gene
      biochemically, a recombinant human protein was produced in an Escherichia coli
      expression system. The full-length protein, p110RB, and an amino-terminal
      truncated form, p56RB, were expressed and purified to near homogeneity by
      conventional chromatographic procedures. To probe the structural organization of
      the retinoblastoma protein the purified proteins were subjected to partial
      proteolysis by trypsin, chymotrypsin, and subtilisin. Four discrete structural
      domains were revealed in p110RB by this method. Two of these structural domains,
      found in both p56RB and p110RB, were mapped to the carboxyl-terminal half of the
      protein and corresponded to the SV40 large T binding domains defined previously
      by genetic methods. In addition two distinct domains in the amino-terminal half
      of the protein were also defined. A potential role for these newly defined amino
      terminal domains was uncovered upon analysis of the purified proteins by
      nondenaturing polyacrylamide gel electrophoresis. p110RB revealed multiple bands
      by this method, suggesting the formation of oligomeric structures by the protein,
      while this property was not observed for p56RB. Electron microscopy of p110RB
      revealed linearly extended, macromolecular structures, further supporting the
      formation of homologous higher order structures by the full-length retinoblastoma
      protein. Analysis of the interactions between retinoblastoma protein molecules
      using the yeast two-hybrid system confirmed that the retinoblastoma protein could
      self-associate and that this association was mediated by interactions between the
      amino- and carboxyl-terminal ends of the protein. These observations suggest that
      the retinoblastoma protein contains multiple structural domains with the amino
      terminal domains being required for oligomerization of the full-length protein.

PMID- 8288606
TI  - Cloning of a novel alpha 2,3-sialyltransferase that sialylates glycoprotein and
      glycolipid carbohydrate groups.
AB  - Sialyltransferases are a family of 10-12 enzymes that catalyze the transfer of
      sialic acid to carbohydrate groups of glycoproteins and glycolipids. Three
      sialyltransferase cDNAs have been cloned, revealing a highly conserved
      sialylmotif in the catalytic domain of these enzymes. Using a polymerase chain
      reaction-based approach, we cloned a 150-base pair fragment of a new sialymotif
      from human placenta mRNA, which was then used as a probe to clone the complete
      coding sequence of the corresponding gene from a cDNA library. Like the other
      members of the sialyltransferase gene family cloned to date, the new cDNA coded
      for a protein predicted to have an NH2-terminal signal-anchor sequence and had
      the sialylmotif located in the center of the molecule. Comparison with the three
      other cloned sialyltransferases revealed extensive sequence homology that was not
      recognized earlier. Expression of a soluble recombinant form of the protein in
      COS-1 cells produced an active sialyltransferase, which used oligosaccharide,
      glycoprotein, and glycolipid acceptor substrates with terminal galactose in the
      Gal beta 1,3GalNAc and Gal beta 1, 4GlcNAc sequences but not the Gal beta
      1,3GlcNAc sequence. The sialylated products were sensitive to digestion with the
      Newcastle disease virus sialidase, which is specific for sialic acid-galactose
      linkages in the alpha 2,3 linkage. The results suggest that this new member of
      the sialyltransferase gene family is the enzyme previously described as a
      glycolipid sialyltransferase activity (SAT-3), which forms the terminal sequences
      NeuAc alpha-2,3Gal beta 1,3GalNAc-R and NeuAc alpha 2,3Gal beta 1, 4GlcNAc-R.

PMID- 8288607
TI  - Molecular cloning and expression of GalNAc alpha 2,6-sialyltransferase.
AB  - cDNA clones encoding GalNAc alpha 2,6-sialyltransferase (EC 2.4.99.3) have been
      isolated from chick embryo cDNA libraries using sequence information obtained
      from the conserved amino acid sequence of the previously cloned enzymes. The cDNA
      sequence included an open reading frame coding for 566 amino acids, and the
      deduced amino acid sequence showed 12% identity with that of Gal beta 1,4GlcNAc
      alpha 2,6-sialyltransferase from chick embryo. The primary structure of this
      enzyme suggested a putative domain structure, like that in other
      glycosyltransferases, consisting of a short NH2-terminal cytoplasmic domain, a
      signal-membrane anchor domain, a proteolytically sensitive stem region, and a
      large COOH-terminal active domain. The identity of this enzyme was confirmed by
      the construction of a recombinant sialyltransferase in which the NH2-terminal
      part (232 amino acid residues) was replaced with the immunoglobulin signal
      sequence. The expression of this recombinant in COS-7 cells resulted in secretion
      of a catalytically active and soluble form of the enzyme into the medium. The
      expressed enzyme exhibited activity toward only asialomucin and (asialo)fetuin,
      no significant activity being detected toward the other glycoprotein and
      glycolipid substrates tested. 14C-Sialylated glycols obtained from asialomucin re
      sialylated with this enzyme were identical to NeuAc alpha 2,6-GalNAc-ol and
      GlcNAc beta 1,3(NeuAc alpha 2,6) GalNAc-ol. Synthetic GalNAc-SerNAc also served
      as an acceptor for alpha 2,6-sialylation. These results clearly showed that the
      expressed enzyme is GalNAc alpha 2,6-sialyltransferase.

PMID- 8288608
TI  - A sarco/endoplasmic reticulum Ca(2+)-ATPase 3-type Ca2+ pump is expressed in
      platelets, in lymphoid cells, and in mast cells.
AB  - An organellar-type of Ca2+ pump formerly detected by means of its phosphoprotein
      intermediate in platelets and in lymphoid cells, and which runs in acid gels at
      97 kDa, is now characterized as sarco/endoplasmic reticulum Ca2+ATPase 3
      (SERCA3). SERCA3 is co-expressed in these cells along with the housekeeping
      SERCA2b. This conclusion is based on the following observations. 1) Tryptic
      digestion the phosphoprotein intermediate of SERCA3 expressed in COS cells yields
      a phosphorylated fragment of about 80 kDa, which can be clearly distinguished
      from the 57-kDa fragments formed in the SERCA1 and SERCA2 pumps. This 80-kDa
      fragment comigrates with a similar phosphoprotein fragment previously observed in
      human platelets (Papp, B., Enyedi, A., Paszty, K., Kovacs, T., Sarkadi, B.,
      Gardos, G., Wuytack, F., and Enouf, J. (1992) Biochem. J. 288, 297-302). 2) An
      antiserum directed against an NH2-terminal SERCA3-specific peptide (N89) reacts
      with SERCA3 expressed in COS cells and with the 97-kDa protein in rat platelets
      and the corresponding protein in human platelets. Likewise an antiserum against
      the rat SERCA3 terminus (C90) binds to SERCA3 expressed in COS cells and to the
      97-kDa band in rat platelets, but it does not recognize the human platelet pump.
      In conformity with the predicted absence of the T1 tryptic cleavage site in
      SERCA3, the autophosphorylated aspartyl residue and the COOH-terminal epitope
      were co-localized on the 80-kDa fragment. 3) The co-expression of nearly equal
      levels of SERCA3 and SERCA2b messengers in human lymphoblastoid Jurkat cells and
      in proliferating rat mucosal mast cells was also demonstrated by reverse
      transcriptase polymerase chain reaction.

PMID- 8288609
TI  - The rat platelet 97-kDa Ca2+ATPase isoform is the sarcoendoplasmic reticulum
      Ca2+ATPase 3 protein.
AB  - We recently showed that human and rat platelets express two types of SERCAs
      (Sarco Endoplasmic Reticulum Ca2+ATPases): a 100-kDa SERCA2b isoform and a 97-kDa
      SERCA isoform. Here, we explored the possibility that the rat 97-kDa isoform is
      identical to the SERCA3 protein. For this purpose, we first attempted to detect
      SERCA3 mRNA in rat platelet total RNA by reverse transcription-polymerase chain
      reaction using SERCA3-specific primers, and demonstrated the presence of this
      mRNA species by sequencing the amplification product. We then searched for a
      relationship between the expression of the SERCA3 mRNA and of the 97-kDa protein
      using either rat aortic smooth muscle cells, previously found not to express the
      97-kDa SERCA isoform (negative model), or platelets of spontaneously hypertensive
      rats (SHR), which overexpress this isoform (overexpression model) but express the
      100-kDa SERCA2b isoform normally. No expression of SERCA3 mRNA was detectable by
      analysis of smooth muscle cell RNA, but comparison by reverse transcription
      polymerase chain reaction of the SERCA2b and SERCA3 mRNAs from the platelets of
      normotensive (Wistar-Kyoto, WKY) rats and SHR clearly demonstrated a 238 +/- 43%
      increase in the expression of the SERCA3 mRNA in SHR platelets only. Last, by
      comparative Western blotting of WKY rat and SHR platelet membranes using a
      recently developed polyclonal anti-SERCA3 antibody, we established that the 97
      kDa SERCA and the SERCA3 protein are identical, as immunostaining of the 97-kDa
      protein revealed a 230 +/- 25% increase in the expression of this protein in SHR
      versus WKY rat platelets. It is concluded that the 97-kDa platelet SERCA isoform,
      which is up-regulated in SHR, is the SERCA3 protein. As far as we know, this
      constitutes the first demonstration of the actual presence of this Ca2+ATPase
      isoform in normal cells, in addition to the artificial transfection systems.

PMID- 8288610
TI  - Dominant inhibitory mutants of ARF1 block endoplasmic reticulum to Golgi
      transport and trigger disassembly of the Golgi apparatus.
AB  - Using three different trans dominant mutants of bovine ARF1 affecting GDP
      exchange or GTP hydrolysis we demonstrate the central role of ARF1 in controlling
      vesicular traffic from the endoplasmic reticulum (ER) to the Golgi apparatus and
      between successive Golgi compartments. Overexpression of ARF1(Q71L), a mutant
      likely to be restricted to the GTP-bound form, resulted in the accumulation of
      vesicular stomatitis virus glycoprotein in pre-Golgi intermediates, inhibited
      transport between successive Golgi compartments, and led to a striking
      association of beta-COP with pre-Golgi intermediates and the Golgi stack. In
      contrast, ARF1(T31N), a mutant which is likely to have a preferential affinity
      for GDP compared to the wild-type protein, inhibited export from the ER and
      triggered a brefeldin A-like phenotype, resulting in the redistribution of beta
      COP from Golgi membranes to the cytosol and the collapse of the Golgi into the
      ER. This mutant, which may efficiently sequester an ARF-specific guanine
      nucleotide-exchange protein (ARF-GEF), suggests that ARF and ARF-GEF are
      essential for export from the ER. These results are discussed in the context of
      the GDP and GTP-bound forms of ARF in controlling both membrane structure and
      vesicular traffic through the early secretory pathway.

PMID- 8288611
TI  - Repression of mouse mammary tumor virus transcription by a transcription factor
      complex. Binding of individual components to separated DNA strands.
AB  - Expression of mouse mammary tumor virus in T lymphocytes appears to be required
      for accession of horizontally transmitted virus to the mammary gland. Further,
      deletions in the long terminal repeat which relax constraints on viral
      transcription promote T cell lymphoma. We have identified a polypurine
      transcriptional repressor element (NRE1) that is deleted from viruses that induce
      T cell lymphoma. NRE1 binding activity in nuclear extracts proved to be related
      to a growth inhibitory activity that represses c-myc expression in mature B
      cells. Mobility shift, DNA footprinting, and UV cross-linking identified three
      factors that interacted preferentially with double-stranded NRE1 or the separated
      single strands. NRE1 binding factor (NBF) (80 kDa) bound double and upper strand
      NRE1, apparently in concert with NRE1 associated factor (NAF) (95 kDa), which
      interacted directly with DNA only on the upper strand. NRE1 lower strand binding
      factor (NLF) (50 kDa) cross-linked specifically to lower strand NRE1. On sucrose
      gradients NBF, NAF, and NLF binding activities cosedimented at 8 S, implying an
      in vitro association of the 50-, 80-, and 95-kDa factors which precedes DNA
      binding. Therefore, NRE1 appears to be the site of action of a complex
      transcriptional repressor comprised of at least three factors that interact
      differentially with each DNA strand to repress steroid hormone-induced
      transcription of mouse mammary tumor virus in T cells.

PMID- 8288612
TI  - Molecular cloning and characterization of the full-length cDNA encoding the
      developmentally regulated lysosomal enzyme beta-glucosidase in Dictyostelium
      discoideum.
AB  - The developmentally regulated Dictyostelium discoideum lysosomal enzyme beta
      glucosidase is synthesized as a membrane-associated glycosylated precursor
      polypeptide which undergoes at least two proteolytic cleavage events to generate
      a soluble mature lysosomally localized protein. To begin to analyze the
      mechanisms regulating the sorting of this protein and the regulation during
      development of the expression of the encoding gene, we have cloned and sequenced
      a 2.6-kilobase (kb) cDNA which contains a complete 2463-nucleotide open reading
      frame coding for beta-glucosidase. Conceptual translation of this open reading
      frame predicts a polypeptide similar in molecular mass to the primary translation
      product of 94 kDa that also contains the same amino acid sequences of two V8
      protease derived-peptides generated from the purified beta-glucosidase enzyme.
      The D. discoideum enzyme contained regions highly homologous at the amino acid
      sequence level to both bacterial and fungal beta-glucosidases, although these
      regions did not overlap. A potential cleavable signal sequence was also found in
      the first 21 amino acids followed by a highly polar stretch of 49 amino acids
      which (based on amino acid sequencing of the mature beta-glucosidase) represents
      a pro region for this protein. This region is similar in location, size, and
      charge to the D. discoideum alpha-mannosidase pro-I region (Schatzle, J., Bush,
      J., and Cardelli, J. (1992) J. Biol. Chem. 267, 4000-4007). Several small
      hydrophobic stretches of amino acids were also distributed throughout the
      protein; however, no obvious transmembrane region(s) were identified which might
      explain the observed membrane association of the precursor protein. Finally,
      Northern blot analysis indicated that the gene encoding this enzyme was under
      developmental regulation. The steady state level of a 2.7-kb beta-glucosidase
      mRNA decreased significantly during the aggregation stage of development, from
      high levels during growth, and then increased in the form of a larger size 2.8-kb
      mRNA during the final stages of development.

PMID- 8288613
TI  - The carboxyl-terminal domain of kinesin heavy chain is important for membrane
      binding.
AB  - Sea urchin kinesin is a plus end-directed microtubule-based motor consisting of
      two heavy chains and two light chains and is proposed to be responsible (a) for
      the transport of membranous organelles along microtubules in sea urchin mitotic
      spindles (Wright, B. D., Henson, J. H., Wedaman, K. P., Willy, P. J., Morand, J.
      N., and Scholey, J. M. (1991) J. Cell Biol. 113, 817-833) and (b) for the radial
      dispersion of endoplasmic reticulum and endosomal membranes in non-mitotic
      cultured coelomocytes (Henson, J. H., Nesbitt, D., Wright, B. D., and Scholey, J.
      M. (1992) J. Cell Sci. 103, 309-320). We report here that sea urchin kinesin is
      indeed able to bind in a concentration-dependent and saturable manner to
      microsomal membranes isolated from sea urchin eggs in the presence of MgATP. The
      kinesin light chains may not be essential for membrane binding since kinesin
      containing negligible amounts of light chains binds as well as kinesin containing
      stoichiometric amounts of light chains. Finally, we propose that kinesin binds to
      membranes with the carboxyl-terminal domain of the heavy chain (amino acid
      residues 858-1031) since the bacterially expressed and then isolated stalk-tail
      fragment of kinesin heavy chain, in contrast to the stalk fragment, is able (a)
      to bind membranes in a concentration-dependent and saturable manner and (b) to
      compete with native kinesin for membrane binding. Our results support the
      hypothesis that the carboxyl-terminal domains of the heavy chains attach kinesin
      molecules to their membranous cargo in mitotic and interphase sea urchin cells.

PMID- 8288614
TI  - Characterization of a plasma membrane-associated prenylcysteine-directed alpha
      carboxyl methyltransferase in human neutrophils.
AB  - Signal transduction in human neutrophils requires prenylcysteine-directed
      carboxyl methylation of ras-related low molecular weight GTP-binding proteins. We
      now report the subcellular localization and characterization of a neutrophil
      prenylcysteine alpha carboxyl methyltransferase. The highest carboxyl
      methyltransferase activity copurified with biotinylated neutrophil surface
      membranes, supporting a plasma membrane localization of the enzyme. Neutrophil
      nuclear fractions contained little or no methyltransferase activity.
      Methyltransferase activity was detergent-sensitive but could be reconstituted by
      removal of detergent in the presence of phosphatidyl choline and an anionic
      phospholipid. N-Acetyl-S-trans,trans-farnesyl-L-cysteine (AFC) and N-acetyl-S-all
      trans-geranylgeranyl-L-cysteine (AGGC) were effective substrates for neutrophil
      prenylcysteine-directed methyltransferase; Vmax values for AFC and AGGC (16.4 and
      22.1 pmol of methylated/mg protein/min, respectively) are among the highest yet
      reported. Although both GTP gamma S and the chemoattractant fMet-Leu-Phe
      stimulated methylation of ras-related proteins, neither affected methylation of
      AFC. These data suggest that neutrophil plasma membranes contain a phospholipid
      dependent, prenylcysteine-directed carboxyl methyltransferase of relatively high
      specific activity that modifies ras-related protein substrates in the GTP-bound,
      activated state.

PMID- 8288615
TI  - Analyses of beta-thalassemia mutant DNA interactions with erythroid Kruppel-like
      factor (EKLF), an erythroid cell-specific transcription factor.
AB  - We describe functional tests and molecular modeling of erythroid Kruppel-like
      factor (EKLF) interactions with its DNA binding site. EKLF, a zinc finger
      containing, erythroid-specific transcription factor, binds and transactivates
      from the CACCC element, an evolutionarily conserved DNA sequence present within a
      large number of erythroid-specific promoters and enhancers. This DNA binding
      element is the site of naturally occurring point mutations that give rise to beta
      thalassemia. We have directly tested whether CAC site point mutations (including
      two of the beta-thalassemia mutants) affect EKLF transactivation and DNA binding
      function. In vivo analyses demonstrate that EKLF is unable to transactivate a
      reporter plasmid that contains these mutations. In vitro analyses reveal a 40-100
      fold decrease in binding affinity for these sites that accounts for the in vivo
      observations. The homology between the three EKLF and Zif268 zinc fingers and
      their conserved sequence-specific contacts to their target site allowed us to
      formulate a molecular model of the EKLF/CAC site complex, based primarily on
      energy minimization/refinement of the Zif268/DNA co-crystal structure. These
      models suggest that both specific and nonspecific hydrogen bonding play a
      critical role in the ability of EKLF to prefer binding to its cognate site.
      Analysis of sequence-specific contacts by EKLF to its target site within the beta
      globin promoter verified the residues predicted to be important by the functional
      and modeling data. Together these results demonstrate that EKLF displays a strong
      discriminatory ability among potential DNA target sites consistent with the beta
      thalassemia data. They also suggest that lack of EKLF binding to these sites may
      play a determining role in its phenotype, and they strengthen the evidence in
      favor of EKLF's proposed role in erythroid-specific transcriptional activation
      through the CACCC elements.

PMID- 8288616
TI  - Coupled replication-translation of amplifiable messenger RNA. A cell-free protein
      synthesis system that mimics viral infection.
AB  - Amplifiable messenger RNAs (Wu, Y., Zhang, D. Y., and Kramer, F. R. (1992) Proc.
      Natl. Acad. Sci. U.S.A. 89, 11769-11773) were used as templates in coupled
      replication-translation reactions. These amplifiable mRNAs contained a
      preselected messenger sequence embedded within the sequence of MDV-1 RNA, which
      is a small, naturally occurring template for Q beta replicase. When these
      recombinant mRNAs were incubated in vitro in reactions that contained both an
      Escherichia coli cell-free translation system and Q beta replicase, the encoded
      protein was synthesized more efficiently than in corresponding reactions that did
      not contain Q beta replicase. Moreover, when coupled replication-translation
      reactions were carried out in a continuous-flow format (Spirin, A. S., Baranov,
      V. I., Ryabova, L. A., Ovodov, S. Yu., and Alakhov, Yu. B. (1988) Science 242,
      1162-1164), the synthesis of biologically active protein continued for a
      prolonged period. The results suggest that the mechanism of replication and
      translation in coupled reactions is similar to the mechanism by which Q beta
      phage genomic RNA is simultaneously replicated and translated in Q beta-infected
      E. coli: protein synthesis occurs on nascent RNA strands; many more sense strands
      are synthesized than antisense strands; and the integrity of the messenger
      sequence is preserved because a relatively small number of antisense strands
      serve as master templates for the synthesis of new messenger strands.

PMID- 8288617
TI  - Beta A4-amyloid protein precursor mRNA isoforms without exon 15 are ubiquitously
      expressed in rat tissues including brain, but not in neurons.
AB  - The beta A4-amyloid protein precursor (APP), the source of the beta A4-amyloid
      deposits found in Alzheimer brains, constitutes a family of transmembrane
      glycoproteins generated by alternative splicing. While exon 7 and exon 8 are well
      known to be alternatively spliced, APP mRNA isoforms without exon 15 were only
      recently identified in leukocytes and rat brain microglial cells and therefore
      denoted as L-APP mRNAs. In order to perform a detailed analysis of individual L
      APP mRNA isoforms in perfused rat tissues, we developed a quantitative polymerase
      chain reaction assay from reverse transcribed RNA allowing us to analyze the
      alternatively spliced region in between exon 6 and 16. In all peripheral tissues
      examined, L-APP mRNA isoforms were detected comprising between 25% (skeletal
      muscle) and about 70% (aorta, pancreas) of total APP transcripts. All four
      possible APP mRNA isoforms without exon 15 were shown to exist, i.e. L-APP752, L
      APP733, L-APP696, and L-APP677. L-APP expression in the central nervous system
      (approximately 4% of total APP mRNA) was then studied in more detail by analyzing
      different brain regions and tissues and primary cultured brain cells. The only
      cell type which was shown not to express L-APP mRNA to a detectable level is the
      neuronal cell. Ubiquitous expression of APP mRNAs lacking exon 15 except for
      neurons indicates an important function in non-neuronal cells and is especially
      remarkable since neurons are the primarily affected cells in Alzheimer's disease.

PMID- 8288618
TI  - alpha-Actinin and vinculin are PIP2-binding proteins involved in signaling by
      tyrosine kinase.
AB  - Western blot analysis of Balb/c 3T3 cell lysates by an antibody specific to
      phosphatidylinositol 4,5-bisphosphate (PIP2) showed that several proteins exist
      in a PIP2-bound form. Among them, two proteins, 100 and 115 kDa in molecular
      mass, were detected as PIP2 abundant proteins. These were identified as alpha
      actinin and vinculin by their antibodies. In Balb/c 3T3 cells, alpha-actinin in
      the cytoskeleton contains PIP2, while alpha-actinin in cytosol does not. The
      levels of PIP2 bound to alpha-actinin decrease in response to platelet-derived
      growth factor (PDGF). Similarly, PIP2 bound to vinculin is decreased upon
      stimulation with PDGF. By immunofluorescent staining, PIP2 was found to be
      present densely in the central areas around nuclei, microfilament bundles, and
      focal contacts, where alpha-actinin and vinculin are distributed. PDGF
      stimulation decreases the intensity of PIP2 staining in these areas. In this
      paper we suggest that tyrosine kinase-activated phospholipase C hydrolyzes PIP2
      bound to alpha-actinin and vinculin, leading to the simultaneous generation of
      second messengers and reorganization of the cytoskeleton.

PMID- 8288619
TI  - Mutation of the third intracellular loop of the cAMP receptor, cAR1, of
      Dictyostelium yields mutants impaired in multiple signaling pathways.
AB  - Seven-membrane span receptors transduce a wide range of signals across the plasma
      membrane. One member of this family, the cAMP receptor, cAR1, of Dictyostelium,
      mediates some responses (e.g. adenylyl cyclase activation, multicellular
      aggregation) which require G-proteins and others (e.g. Ca2+ influx, loss of
      ligand binding, cAR1 phosphorylation) which appear to be G-protein-independent.
      In this study, we randomly mutagenized the NH2-terminal eight amino acids of the
      third intracellular loop of cAR1 and examined the ability of these mutants to
      exhibit the three G-protein-independent responses listed above. Most mutants
      (classes I, II) exhibited wild-type or midly defective responses. Several mutants
      (class III), however, were severely impaired in all three processes but not in
      cAMP binding. Furthermore, these mutants failed to couple productively with G
      proteins and could not replace cAR1 in a car1- cell. For these reasons, we
      propose that class III mutations interfere with the formation of an "active"
      conformation of the receptor.

PMID- 8288620
TI  - Alteration of Na,K-ATPase subunit mRNA and protein levels in hypertrophied rat
      heart.
AB  - To determine if an altered expression of the Na,K-ATPase alpha isoform genes is
      responsible for an observed increase in cardiac glycoside sensitivity in
      compensatory hypertrophy, we performed Northern and slot blot analyses of RNA and
      specific immunological detection of Na,K-ATPase isoforms in rat hearts from
      normal and pressure overload-treated animals induced by abdominal aortic
      constriction. During the early phase of hypertrophy, the only alteration is a
      decrease in the alpha 2 mRNA isoform. In the compensated hypertrophied heart, the
      levels of the predominant alpha 1 isoform (mRNA and protein) and the beta 1
      subunit mRNA are unchanged. In contrast, the alpha 2 isoform (mRNA and protein)
      is decreased by 35% and up to 61-64% in mild (< 55%) and severe (> 55%)
      hypertrophy, respectively. The alpha 3 isoform (mRNA and protein), which is
      extremely low in adult heart, is increased up to 2-fold during hypertrophy but
      accounts for only approximately equal to 5% of the total alpha isoform mRNA.
      These findings demonstrate that, in cardiac hypertrophy, the three alpha isoforms
      of the Na,K-ATPase are independently regulated and that regulation occurs at a
      pretranslational level. The pattern of expression in hypertrophied adult heart is
      similar to that of the neonatal heart where the inverse regulation between the
      alpha 2 and alpha 3 ouabain high affinity isoforms has been reported. This
      suggests that distinct regulatory mechanisms controlling Na,K-ATPase isoform
      expression may, at least in part, be involved in the sensitivity to cardiac
      glycosides.

PMID- 8288621
TI  - gamma-Aminobutyric acid-A (GABAA) agonists down-regulate GABAA/benzodiazepine
      receptor polypeptides from the surface of chick cortical neurons.
AB  - The impermeant SH-cleavable reagent, 125I-labeled 3,3'-dithiopropionyl 1
      sulfosuccinimidyl 1'-glycyltyrosine (DPSgt) and specific immunoprecipitation were
      used to quantitate gamma-aminobutyric acid-A (GABAA) receptor polypeptides with
      domains exposed on the surface of chick cortical neurons. The 125I label
      incorporated into 50- and 53-kDa receptor subunits was completely removed by
      washing the cells with glutathione (GSH) buffer. A single dose of 100 microns
      GABA or GABA agonist was added to the neurons, and after 5 days in culture the
      cells were washed and labeled with 125I-DPSgt. This treatment with GABA or
      isoguvacine reduced the level of the receptor 125I-labeled subunits by 50-60%,
      while the reduction by 4,5,6,7-tetrahydroisoazolo[5,4-c]pyridin-3-ol was less
      than 17%. The subunit down-regulation by agonist was prevented by the GABAA
      antagonist 3 alpha-hydroxy-16-imino-5 beta-17-aza-androstan-11-one (R5135).
      Direct iodination of membranes isolated from treated cells revealed a similar
      loss of subunits, indicating that the down-regulated polypeptides are not
      retained intracellularly. Furthermore, the level of intracellular
      [3H]flunitrazepam binding (per mg of protein) did not change significantly during
      chronic GABA treatment, while the fraction of intracellular binding rose from 7%
      to 15% of the total, owing to a decline in surface binding. The fate of the
      surface subunits during acute agonist exposure was examined by labeling intact
      neurons with 125I-DPSgt at 0 degrees C, incubating with GABA for 2-4 h at 37
      degrees C and then washing with GSH buffer. Of the 50-53-kDa receptor peptides
      originally on the surface, 16 +/- 2% became protected from GSH during the 2-h
      GABA treatment. This sequestration was not found in cells incubated without GABA,
      with GABA + R5135, or with GABA at 0 degree C. A consistently lower level of
      sequestered subunits was recovered after a 4- versus 2-h GABA treatment at 37
      degrees C, suggesting polypeptide degradation. Overall, the results indicate that
      GABAA receptor sequestration and subsequent degradation play an important role in
      agonist-dependent down-regulation.

PMID- 8288622
TI  - Structure of the L-histidine decarboxylase gene.
AB  - Two species of L-histidine decarboxylase (HDC) mRNA were found in the KU-812-F
      basophilic cell line, but only the 2.4-kilobase (kb) one encodes the functional
      HDC (Mamune-Sato, R., Yamauchi, K., Tanno, Y., Ohkawara, Y., Ohtsu, H., Katayose,
      D., Maeyama, K., Watanabe, T., Shibahara, S., and Takishima, T. (1992) Eur. J.
      Biochem. 209, 533-539). The 3.4-kb one encodes a truncated HDC protein and is
      also found in human leukemia-derived cell lines HEL and KCL-22. To clarify the
      mechanisms that regulate transcription of the HDC gene and generate the two
      species of mRNA, we have isolated genomic DNA clones coding for the HDC from
      human genomic libraries. Structural analysis of the isolated clones revealed that
      the human HDC gene is composed of 12 exons spanning approximately 24 kb. Genomic
      DNA blot analysis suggested that HDC is encoded by a single copy gene. The
      structural analysis also demonstrated that the heterogeneity of the HDC mRNA is
      caused by an insertion of the seventh intron sequence and alternative use of the
      splicing acceptor site at the 12th exon. The transcription start site of the HDC
      gene and the nucleotide sequences of the promoter and first exon regions were
      determined. We found a TATA-like sequence, a GC box, four CACC boxes, four GATA
      consensus sequences, and six leader-binding protein-1 binding motifs in the
      promoter region of the HDC gene.

PMID- 8288623
TI  - A dual role for phosphatidylglycerol in protein translocation across the
      Escherichia coli inner membrane.
AB  - The involvement of phosphatidylglycerol in the SecA-independent translocation of
      M13 procoat in Escherichia coli was demonstrated. Processing of procoat to mature
      coat protein was retarded when the level of phosphatidylglycerol was reduced. In
      vitro translocation experiments using inner membrane vesicles isolated from a
      strain with inducible synthesis of phosphatidylglycerol, showed that
      translocation of procoat and of a SecA-dependent procoat analog was proportional
      to the content of phosphatidylglycerol. Moreover, introduction of
      phosphatidylglycerol by means of a lipid transfer method into
      phosphatidylglycerol-depleted inner membrane vesicles, efficiently restored
      procoat translocation. The phosphatidylglycerol dependence in both the SecA
      dependent and -independent translocation pathway indicates that
      phosphatidylglycerol plays a dual role in translocation. We suggest that besides
      membrane binding of SecA this lipid has a direct interaction with the M13 procoat
      in translocation across the inner membrane.

PMID- 8288624
TI  - Functional domains of aromatase cytochrome P450 inferred from comparative
      analyses of amino acid sequences and substantiated by site-directed mutagenesis
      experiments.

PMID- 8288625
TI  - Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA
      repair.
AB  - The anticancer drug cisplatin provokes a complex response in the cell. A lethal
      dose of the drug kills cells primarily by forming DNA adducts, causing G2 arrest
      in the cell cycle, and then triggering apoptosis. A sublethal dose induces drug
      resistance by several mechanisms, including changes in drug uptake and efflux,
      glutathione and metallothionein levels, and DNA repair. Cisplatin-DNA adducts
      bind several cellular proteins, including some that enhance survival of the cell
      by mediating DNA repair and others that hasten its death by conferring
      sensitivity to the drug.

PMID- 8288626
TI  - Removal of Rab GTP-binding proteins from Golgi membranes by GDP dissociation
      inhibitor inhibits inter-cisternal transport in the Golgi stacks.
AB  - Rab proteins are a family of Ras-like GTPases involved in intracellular membrane
      traffic. Rab GDI, a cytosolic protein which inhibits the dissociation of GDP from
      various Rab proteins, is required to maintain a pool of Rab proteins in the
      cytosol. We describe the purification of a cytosolic factor from bovine liver
      that inhibits intra-cisternal transport between the Golgi stacks. We identify
      this factor as a Rab GDI. Half-maximal inhibition of transport was observed in
      the presence of the same concentration of GDI that is required for removal of Rab
      proteins from the Golgi.

PMID- 8288627
TI  - Lipid hydroperoxides induce apoptosis in T cells displaying a HIV-associated
      glutathione peroxidase deficiency.
AB  - 8E5 is a chronically human immunodeficiency virus (HIV)-infected human T cell
      line, which we have previously shown to be extremely susceptible to hydrogen
      peroxide (H2O2)-induced apoptosis due to a HIV-associated catalase deficiency.
      Here we report that HIV gene expression additionally renders 8E5 cells 10-fold
      more sensitive than either uninfected A3.01 cells or HIV-infected but
      nonexpressing 8E5L cells to killing by 15-hydroperoxyeicosatetraenoic acid (15
      HPETE), as well as several other hydroperoxy fatty acids. Whereas the viability
      of A3.01 and 8E5L cells was relatively unaffected by exposure to 10 microM 15
      HPETE, similarly treated 8E5 cells underwent apoptosis, as demonstrated by
      morphological changes and the presence of fragmented DNA. The unique
      susceptibility of 8E5 cells was attributable to their inability to convert 15
      HPETE to 15-hydroxy-eicosatetraenoic acid (15-HETE) owing to a marked reduction
      in glutathione peroxidase activity. Since oxidized lipids have been reported to
      accumulate in oxidatively stressed, HIV-infected individuals, a HIV-associated
      glutathione peroxidase deficiency may contribute to the depletion of CD4 T cells
      that occurs in the acquired immune deficiency syndrome (AIDS).

PMID- 8288628
TI  - Active site mapping of affinity-labeled rat oxidosqualene cyclase.
AB  - Rat liver oxidosqualene cyclase (OSC), a 78-kDa membrane-bound enzyme, was
      purified and labeled with the mechanism-based irreversible inhibitor, [3H]29
      methylidene-2,3-oxidosqualene (Abe, I., Bai, M., Xiao, X.-Y., and Prestwich, G.
      D. (1992) Biochem. Biophys. Res. Commun. 187, 32-38). A 6-kDa CNBr peptide was
      separated by Tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      and blotted to a polyvinylidene difluoride membrane. The sequence of the first 30
      amino acids of this peptide were determined by Edman degradation and showed
      unexpectedly high similarity to the fungal OSC from Candida albicans (50%
      identity with Arg413-Val442) and to the bacterial squalene cyclase from
      Alicyclobacillus (formerly Bacillus) acidocaldarius (37% identity with Lys356
      Leu385). Further, radioanalysis clearly established that the two adjacent Asp
      residues in the highly conserved region (Asp-Asp-Thr-Ala-Glu-Ala or DDTAEA) were
      equally labeled by the irreversible inhibitor. This result provides the first
      information on the structural details of the active site of OSC and shows for the
      first time the ancient lineage of this vertebrate enzyme to ancestral eukaryotic
      and prokaryotic cyclases. Interestingly, the covalently modified DDXX(D/E)
      sequence of rat liver OSC showed surprising similarity to the putative allylic
      diphosphate binding site sequence of sesquiterpene cyclases and prenyl
      transferases.

PMID- 8288629
TI  - A novel cytokine exhibiting megakaryocyte potentiating activity from a human
      pancreatic tumor cell line HPC-Y5.
AB  - Sixty-four kinds of cell lines were examined for their ability to produce
      megakaryocyte potentiating activity by means of conditioned media obtained from a
      protein-free culture system. Six human tumor cell lines were shown to produce
      this activity, and the cell line HPC-Y5, established from human pancreatic
      cancer, was shown to have the highest level of activity. The megakaryocyte
      potentiating factor (MPF) was purified from an HPC-Y5 conditioned medium by a
      combination of ion-exchange chromatography, gel filtration and reverse-phase
      HPLC. The purified MPF showed a megakaryocyte potentiating activity almost equal
      to human interleukin-6 in the presence of murine interleukin-3 in a colony
      formation assay with mouse bone marrow cells. The apparent molecular weight of
      MPF is 32,000 when determined by SDS-polyacrylamide gel electrophoresis.
      Glycopeptidase F digestion, and amino sugar analysis of the factor demonstrated
      that MPF is a glycoprotein carrying at least one N-linked sugar chain. The N
      terminal amino acid sequence of MPF was determined to be Leu-Ala-Gly-Glu-Thr-Gly
      Gln-Glu-Ala-Ala-Pro-Leu- Asp-Gly-Val-Leu-Ala-Asn. The same or homologous amino
      acid sequence has not been found in known proteins, demonstrating that MPF is a
      novel cytokine that has megakaryocyte potentiating activity in the murine assay
      system.

PMID- 8288630
TI  - Inhibition of human HL-60 cell responses to chemotactic factors by antisense
      messenger RNA depletion of G proteins.
AB  - Chemotactic factors bound to receptors of the seven-transmembrane domain family
      signal leukocytes through associated guanine nucleotide-binding (G) proteins.
      Human leukocytes of the HL-60 line, which express G protein-coupled receptors for
      leukotriene B4 (LTB4) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) after
      differentiation with vitamin D3 and transforming growth factor-beta, were
      transfected with expression plasmids containing antisense-oriented cDNAs encoding
      the alpha-chains of Go, Gi1, Gi2, and Gi3. Antisense mRNA for Go and Gi2 alpha
      chains suppressed by over 80% the level of the respective G protein. Go-deficient
      HL-60 cells had depressed functional and intracellular calcium responses to LTB4
      and fMLP, but no alterations in the responses of cyclic adenosine 3',5'
      monophosphate (cAMP). In contrast, HL-60 cells deficient in Gi2 lost only
      responses of the intracellular concentration of cAMP. Antisense mRNA suppression
      of distinct G proteins thus may delineate some transductional requirements for
      cellular responses.

PMID- 8288631
TI  - Expression of a cloned protoporphyrinogen oxidase.
AB  - The previously cloned hem Y gene of Bacillus subtilis (Hansson, M., and
      Hederstedt, L. (1992) J. Bacteriol. 174, 8081-8093) has been expressed in
      Escherichia coli. The expressed protein has been shown to be the penultimate
      enzyme of the heme biosynthetic pathway, protoporphyrinogen oxidase (EC 1.3.3.4)
      and, thus, the gene designation should be hem G. This represents the first report
      of the expression of a cloned protoporphyrinogen oxidase from any source. The
      enzyme is present in the soluble cytoplasmic fraction and is, thus, unlike all
      previously reported eukaryotic or prokaryotic protoporphyrinogen oxidases, which
      are membrane-bound. It utilizes molecular oxygen as a terminal electron acceptor,
      and protoporphyrinogen IX, mesoporphyrinogen IX, and coproporphyrinogen III serve
      as substrates. The diphenyl ether herbicide acifluorfen, which is a strong
      inhibitor of the eukaryotic enzyme, is only weakly inhibitory. The enzyme has a
      predicted molecular weight of 51,200, which corresponds well with molecular
      weight determination via high performance liquid chromatography and SDS
      polyacrylamide gel electrophoresis. In addition the enzyme contains a putative
      dinucleotide binding region at the amino terminus, which is consistent with the
      previously demonstrated presence of a flavin moiety in the characterized
      mammalian enzymes.

PMID- 8288632
TI  - Phosphatidylethanolamine incorporation into vesicles selectively enhances factor
      Va inactivation by activated protein C.
AB  - Membrane surfaces accelerate the proteolytic inactivation of factor Va by
      activated protein C. In most coagulation complexes, the most active membrane
      phospholipid is believed to be phosphatidylserine. In this study, we demonstrate
      that with phosphatidylserine-containing vesicles, incorporation of
      phosphatidylethanolamine increased the rate of factor Va inactivation
      approximately 10-fold at all concentrations of factor Va studied and at all
      vesicle concentrations at or below the optimum for prothrombin activation. In
      contrast, phosphatidylethanolamine had very little influence on prothrombin
      activation. Phosphatidylethanolamine was a critical component of vesicles for the
      vesicles to support activated protein C anticoagulant activity optimally in
      plasma. These results demonstrate that the membrane requirements for the
      different coagulation/anticoagulation complexes differ much more than previously
      appreciated.

PMID- 8288633
TI  - Characterization of a promiscuous GTPase-activating protein that has a Bcr
      related domain from Caenorhabditis elegans.
AB  - Human breakpoint cluster region (bcr) gene product is a member of a group of
      GTPase-activating proteins that act exclusively on members of the Ras-related Rho
      subfamily. A complementary DNA was isolated from Caenorhabditis elegans that
      encoded a polypeptide of 1438 amino acid residues, CeGAP, which contains a domain
      with sequence similarity to the COOH-terminal segment (GTPase-activating protein
      region) of Bcr and other known GTPase-activating proteins of the Rho subfamily.
      It also contains a "pleckstrin homology" motif, present in many signaling
      proteins including GTPase-activating proteins and nucleotide exchange factors.
      The Bcr-like domain of CeGAP exhibited activity not only on members of the C.
      elegans and human Rho subfamily but surprisingly also on C. elegans Ras protein
      (let-60), human Ras, and Rab3A. CeGAP is therefore the first GTPase-activating
      protein acting on Ras-related proteins across different subfamilies. Together
      with the presence of the pleckstrin homology motif, our finding suggests a
      central and integrative role for CeGAP in a signaling pathway common to Ras and
      related proteins.

PMID- 8288634
TI  - Rat liver Kupffer and endothelial cells express different binding proteins for
      modified low density lipoproteins. Kupffer cells express a 95-kDa membrane
      protein as a specific binding site for oxidized low density lipoproteins.
AB  - The liver is the major organ responsible for the uptake of oxidized low density
      lipoproteins (Ox-LDL) from the blood circulation with Kupffer cells as major
      cellular uptake site. Candidate binding proteins for Ox-LDL on membranes from
      Kupffer and endothelial liver cells were identified with ligand blots. Under
      nonreducing conditions, a major binding protein with an estimated molecular mass
      of 95 kDa and a minor stained protein of 220 kDa were detected on Kupffer cell
      membranes, while endothelial cell membranes expressed only a 220-kDa binding
      protein. Both the 95-kDa protein of Kupffer cell membranes and the 220-kDa
      protein of endothelial membranes displayed saturable binding of 125I-Ox-LDL with
      a Kd of 15 and 5 micrograms/ml, respectively. LDL was a weak competitor for the
      binding of 125I-Ox-LDL to the 95-kDa protein, while the degree of competition
      appeared to be dependent on the oxidation grade of LDL with a complete
      competition with LDL oxidized for 20 h with 10 microM Cu2+. We conclude that the
      95-kDa binding protein, highly concentrated on rat Kupffer cells, forms the most
      likely candidate for mediating the in vivo uptake of Ox-LDL from the blood
      circulation.

PMID- 8288635
TI  - Brain-derived neurotrophic factor increases neurotrophin-3 expression in
      cerebellar granule neurons.
AB  - Neurotrophin-3 (NT-3) is a member of the neurotrophin gene family and is highly
      expressed in the developing rat cerebellum. Here we show that brain-derived
      neurotrophic factor (BDNF) increased by approximately 10-fold the NT-3 mRNA
      levels in cultured cerebellar granule neurons isolated from postnatal rats,
      whereas nerve growth factor (NGF) and NT-3 itself had no effect. The effect of
      BDNF was additive to that of triiodothyronine (T3), which also increased NT-3
      mRNA in these neurons. The drug K252a inhibited the BDNF-mediated stimulation of
      NT-3 expression, suggesting an involvement of trkB receptors. Nuclear run-on
      experiments showed that BDNF enhanced NT-3 transcription, whereas the stability
      of NT-3 mRNA remained unchanged. The data presented are the first demonstration
      that one neurotrophin regulates the expression of another and provide evidence
      that NT-3 production in granule neurons is regulated by both BDNF and T3.

PMID- 8288636
TI  - Lead activation of protein kinase C from rat brain. Determination of free
      calcium, lead, and zinc by 19F NMR.
AB  - Lead (Pb2+) has been reported to activate calcium/phospholipid-dependent protein
      kinase C (PKC) at subnanomolar concentrations (Markovac, J., and Goldstein, G. W.
      (1988) Nature 334, 732-734); however, others have failed to find any Pb(2+)
      induced activation of PKC (Murakami, K., Feng, G., and Chen, S. G. (1993) J.
      Pharmacol. Exp. Ther. 264, 757-761). In neither of these studies was the actual
      free Pb2+ or Ca2+ concentration measured. In this study, 1,2-bis(2-amino-5
      fluorophenoxy)ethane N,N,N',N'-tetraacetic acid (5F-BAPTA) was used to buffer
      Pb2+ and Ca2+ concentrations in the PKC reaction mixture. The specific free ion
      concentrations of Pb2+ and Ca2+, as well as Zn2+ and other divalent cations
      contained in the PKC reaction mixtures, were determined by 19F NMR spectroscopy.
      Using this approach to set and confirm the free Pb2+ and Ca2+ concentrations, we
      measured the Pb(2+)-dependent and the Ca(2+)-dependent activation of
      phosphotydylserine/diolein-dependent incorporation of 32P from ATP into histone
      and endogenous acid precipitable proteins in the 100,000 x g supernatant from
      homogenized rat brain cortex. We found that free Pb2+ activates PKC in the range
      from 10(-11) to 10(-8) M, Kact = 5.5 x 10(-11) M, while Ca2+ activates PKC in the
      range from 10(-8) to 10(-5) M, Kact = 2.56 x 10(-7) M. These findings clearly
      resolve the activation of PKC by subnanomolar concentrations of free Pb2+ from
      activation induced by Ca2+ or other divalent cations. Furthermore, it documents
      the utility of 5F-BAPTA as buffer and indicator when resolving the contributions
      of multiple divalent cations in biochemical processes.

PMID- 8288637
TI  - Activation and desensitization of phospholipase D in intact rat hepatocytes.
AB  - Activation of phospholipase D (PLD) by receptor-coupled stimuli (vasopressin,
      ATP), phorbol esters, and Ca2+ ionophores was studied in isolated rat
      hepatocytes, double labeled with [3H]arachidonate and [14C]stearate.
      Phosphatidylethanol (Peth) was formed when cells were stimulated in the presence
      of ethanol. The effect of combinations of agonists was not additive, indicating
      that the same PLD isozyme(s) were activated. With all agonists, the 3H- and 14C
      specific radioactivity in Peth was higher than in any of the main phospholipid
      classes. The 3H/14C ratios of Peth and phosphatidylcholine (PC) were identical
      and differed from other phospholipid classes, indicating that the predominant PLD
      substrate was a PC pool labeled preferentially with radioactive fatty acids.
      Ethanol (50-300 mM) decreased the initial rate of phosphatidic acid (PA)
      formation, but did not affect total PLD activity. Agonist-induced changes in
      steady state accumulation of PA or 1,2-diacylglycerol were also unaffected. A
      slow degradation of Peth (apparent t1/2 > 60 min) occurred after ethanol removal
      from cells prestimulated with vasopressin. The rate of degradation was unaffected
      by agonists that stimulate PLD. Thus, Peth formation is a suitable cumulative
      indicator for PLD activation in intact hepatocytes. Peth accumulation declined
      over a period of 5-20 min, depending on the agonist. The decline was not due to
      increased Peth degradation, or limitations in substrate supply to PLD, or enzyme
      inhibition by accumulated Peth. Instead, a homologous desensitization of PLD
      occurs with all agonists. This desensitization may involve the action of
      selective protein kinase C isozymes.

PMID- 8288638
TI  - The role of cytosolic Ca2+, protein kinase C, and protein kinase A in hormonal
      stimulation of phospholipase D in rat hepatocytes.
AB  - Ca(2+)-dependent and protein kinase C-dependent mechanisms of phospholipase D
      (PLD) activation were studied in rat hepatocytes by measuring phosphatidylethanol
      (Peth) formation in the presence of ethanol. Stimulation of Peth formation by 12
      O-tetradecanoyl-phorbol 13-acetate (TPA), vasopressin, or A23187 was inhibited by
      multiple protein kinase C inhibitors or by protein kinase C down-regulation,
      indicating that this enzyme is involved in the action of all these agents. A
      controlled elevation of the cytosolic Ca2+ concentration ([Ca2+]cyt) over the
      range of 0.1-2.0 microM activated Peth formation in the absence of other
      agonists. Staurosporin potentiated Ca(2+)-induced Peth formation by shifting the
      [Ca2+]cyt dose-response curve to the left. Other protein kinase C inhibitors
      (calphostin C, bisindolylmaleimide) inhibited Ca(2+)-mediated Peth formation, but
      this inhibition was reduced in staurosporin-treated cells. Okadaic acid
      potentiated PLD activation by TPA, but suppressed PLD activation by elevated
      [Ca2+]cyt. Desensitization of TPA-induced PLD activity did not affect PLD
      activation by Ca2+. These data indicate that [Ca2+]cyt and protein kinase C
      control distinct pathways of PLD activation, but the Ca(2+)-mediated pathway is
      suppressed by a staurosporin-sensitive protein kinase. Both mechanisms contribute
      to vasopressin-induced Peth formation in intact hepatocytes. Activation of
      protein kinase A enhanced vasopressin-induced Peth formation, but not TPA
      stimulated or Ca(2+)-stimulated stimulated Peth formation. Protein kinase A acted
      by enhancing hormonal Ca2+ mobilization, rather than by directly activating PLD,
      and thereby shifted the balance of Ca(2+)-dependent and protein kinase C
      dependent activation mechanisms of PLD in intact cells.

PMID- 8288639
TI  - Functional coupling of Na+/H+ and Na+/Ca2+ exchangers in the alpha 1
      adrenoreceptor-mediated activation of hepatic metabolism.
AB  - The purpose of this study was to characterize the role of ions other than Ca2+ in
      hepatic responses to alpha 1-adrenergic stimulation. We report that the alpha 1
      adrenoreceptor activation of hepatic functions is accompanied by extracellular
      acidification and an increase in intracellular pH. These effects are dependent on
      extracellular Na+ concentration and are inhibited by the Na+/H+ antiporter
      blocker 5-(N-ethyl-N-isopropyl) amiloride under conditions that preclude
      antagonistic effects on agonist binding. Thus, the activation of plasma membrane
      Na+/H+ exchange is an essential feature of the hepatic alpha-adrenoreceptor
      coupled signaling pathway. The following observations indicate that the sustained
      hepatic alpha 1-adrenergic actions rely on a functional coupling between the
      plasma membrane Na+/H+ and Na+/Ca2+ exchangers, resulting in the stimulation of
      Ca2+ influx. 1) Inhibition of the Na+/K(+)-ATPase does not prevent the alpha 1
      adrenergic effects. However, alpha 1-adrenoreceptor stimulation fails to induce
      intracellular alkalinization and to acidify the extracellular medium in the
      absence of extracellular Ca2+. 2) A non-receptor-induced increase in
      intracellular Na+ concentration, caused by the ionophore monensin, stimulates
      Ca2+ influx and increases vascular resistance. 3) Inhibition of Na+/Ca2+ exchange
      prevents, in a concentration-dependent manner, most of the alpha 1-agonist
      induced responses. 4) The actions of Ca(2+)-mobilizing vasoactive peptide
      receptors or alpha 2-adrenoreceptors, which produce neither sustained
      extracellular acidification nor release of Ca2+, are insensitive to Na+/H+
      exchange blockers.

PMID- 8288640
TI  - Identification of Lys277 at the active site of Escherichia coli glycogen
      synthase. Application of affinity labeling combined with site-directed
      mutagenesis.
AB  - Lys15 in Escherichia coli glycogen synthase, which is specifically labeled by
      adenosine diphosphopyridoxal, is mainly involved in binding of the substrate ADP
      glucose (Furukawa, K., Tagaya, M., Tanizawa, K., and Fukui, T. (1993) J. Biol.
      Chem. 268, 23837-23842). We have found that the mutant glycogen synthase in which
      Lys15 is replaced by Gln via site-directed mutagenesis is inactivated by
      adenosine diphosphopyridoxal at concentrations higher than those required for the
      inactivation of the wild-type enzyme. ADP and ADP-glucose offered protective
      effects on inactivation, suggesting that the label binds to the ADP-glucose
      binding site in the mutant enzyme. Sequence analysis of the labeled peptide
      revealed that the labeled residue is Lys277. This lysyl residue is conserved in
      maize starch synthase, which shows about 30% amino acid identity to E. coli
      glycogen synthase. Substitution of Gln for Lys277 by site-directed mutagenesis
      resulted in a 140-fold decrease in the kcat value with little changes in the Km
      values for ADP-glucose and glycogen. These results suggest that Lys277 at the
      active site participates in the catalytic reaction rather than binding of
      substrate. The present study shows the usefulness of the combined application of
      affinity labeling and site-directed mutagenesis.

PMID- 8288641
TI  - Activation of Raf-1 and mitogen-activated protein kinases during monocytic
      differentiation of human myeloid leukemia cells.
AB  - Treatment of human myeloid leukemia cells with 12-O-tetradecanoylphorbol-13
      acetate (TPA), an activator of protein kinase C (PKC), is associated with
      induction of monocytic differentiation. Since PKC can act immediately upstream to
      the cytoplasmic Raf-1 serine/threonine protein kinase, we studied activation of
      Raf-1 during induction of the differentiated monocytic phenotype. The results
      demonstrate that Raf-1 is activated during TPA-induced monocytic differentiation
      of HL-60 cells. In contrast, there was little effect of TPA on this kinase in an
      HL-60 variant, designated HL-525, which is resistant to TPA-induced
      differentiation. Treatment of both HL-60 and HL-525 cells with okadaic acid, an
      inhibitor of serine/threonine protein phosphatases 1 and 2A, was associated with
      Raf-1 activation and induction of the monocytic phenotype. Since Raf-1 can
      activate the mitogen-activated protein (MAP) kinases, we also studied the
      relationship between MAP kinase activation and monocytic differentiation.
      Treatment of HL-60, but not HL-525, cells with TPA was associated with increased
      MAP kinase activity as determined by phosphorylation of myelin basic protein and
      the c-Jun Y peptide. Okadaic acid-induced differentiation of both HL-60 and HL
      525 cells was similarly accompanied by increases in MAP kinase activity. These
      findings indicated that activation of Raf-1/MAP kinase signaling is associated
      with induction of a differentiated monocytic phenotype and that okadaic acid
      bypasses a defect in this cascade in TPA-treated HL-525 cells. While recent
      studies have shown that HL-525 cells are deficient in PKC beta, the present
      results demonstrate that PKC beta expression is up-regulated in the HL-525
      variant by treatment with retinoic acid. The results also demonstrate that
      retinoic acid-treated HL-525 cells respond to TPA with activation of Raf-1 and
      MAP kinase, as well as induction of monocytic differentiation. Taken together,
      the results indicate that activation of Raf-1/MAP kinase signaling is associated
      with monocytic differentiation and that stimulation of serine/threonine protein
      phosphorylation by TPA or okadaic acid is sufficient for reversal of the leukemic
      HL-60 phenotype.

PMID- 8288642
TI  - The interaction of GATA-binding proteins and basal transcription factors with
      GATA box-containing core promoters. A model of tissue-specific gene expression.
AB  - The core promoters of the rat platelet factor 4 (PF4), mouse erythropoietin and
      chicken beta globin genes contain a GATA motif in place of the consensus TATAAA
      site. In the case of the PF4 gene, this site has been shown to play a critical
      role in restricting transcription to the megakaryocyte lineage. In order to
      understand the mechanism of tissue specificity, we investigated the function of
      the GATA box-containing promoters in vitro. Our studies show that the TATA
      binding protein of TFIID is required for initiation of transcription from the
      GATA box-containing promoters. GATA-1 interacts with the core promoter GATA motif
      and inhibits generation of preinitiation complexes. The functional significance
      of the inhibition of preinitiation complexes is supported by in vitro
      transcription assays in which transcription from the PF4 and erythropoietin core
      promoters is suppressed by GATA-1. We also demonstrate that GATA-2 inhibits
      initiation of transcription from the PF4 core promoter. Based on these results,
      we propose a model in which repression of PF4 expression in nonmegakaryocytes is
      mediated, in part, by competition between GATA-binding proteins and basal factors
      for the core promoter.

PMID- 8288643
TI  - The directly repeated RG(G/T)TCA motifs of the rat and mouse cellular retinol
      binding protein II genes are promiscuous binding sites for RAR, RXR, HNF-4, and
      ARP-1 homo- and heterodimers.
AB  - We show here that the element which was previously characterized as a retinoid X
      receptor (RXR)-specific response element (RXRE) in the rat cellular retinol
      binding protein II (CRBPII) gene is not conserved in the mouse gene. However, two
      conserved cis-acting elements (RE2 and RE3) located in the promoter region of the
      mouse and rat CRBPII genes mediate transactivation by retinoic acid receptors
      (RARs) and RXRs in transfected Cos-1, CV-1, and HeLa cells. The element RE3 which
      is the major retinoic acid (RA) response element also binds the transcription
      factors HNF-4 and ARP-1. HNF-4 constitutively activates the mouse CRBPII
      promoter, whereas ARP-1 represses the activation mediated by RARs, RXRs, and HNF
      4. In contrast, RA has no effect on the activity of the mouse CRBPII promoter in
      the human colon carcinoma cell line CaCo-2 which constitutively expresses RAR
      alpha, RAR gamma, RXR alpha, HNF-4, and ARP-1, under conditions where the
      activity of the RAR beta 2 gene promoter is readily induced by RA. Our results
      suggest that the CRBPII gene may not be RA-inducible in tissues expressing HNF-4
      and ARP-1, and that the RA inducibility of the CRBPII gene promoter observed in
      transfection experiments reflects the promiscuous binding of RARs/RXRs to HNF-4
      and ARP-1 response elements.

PMID- 8288644
TI  - Role of the cationic residues arginine 14 and lysine 48 in the function of the
      cardiotonic polypeptide anthopleurin B.
AB  - Polypeptide neurotoxins from sea anemones have been useful biological probes for
      sodium channel function. Cationic residues, specifically Arg-14, which is
      conserved in essentially all known sea anemone toxins, have been generally
      thought to be important determinants of their binding affinity and/or efficacy.
      In the present study, we have constructed site-directed mutants of the
      Anthopleura xanthogrammica toxin anthopleurin B (ApB) at Arg-14 and Lys-48 to
      characterize the roles played by these cationic residues in the biological
      activity of the toxin. Using a bacterial expression system developed in this
      laboratory, we have produced recombinant proteins having three substitutions at
      each of these positions. The proteins produced have been purified to homogeneity
      and have structures and conformational stabilities identical to wild-type ApB. We
      have assayed the mutants by determining their ability to enhance the veratridine
      dependent uptake of sodium by both N1E-115 neuroblastoma cells and RT4-B cells,
      which express the cardiac/denervated skeletal muscle sodium channel. All mutants
      showed activities only slightly reduced from that of wild-type ApB, with the
      greatest reductions (4- and 6-fold) being observed for the mutants R14A and K48A,
      respectively. We conclude that contrary to results from chemical modification
      studies, Arg-14 is not essential for the biological activity of the toxin. Our
      data also indicate that Lys-48 plays a small but discernible role in the toxin
      receptor interaction.

PMID- 8288645
TI  - Characterization of the retention motif in the C-terminal part of the long splice
      form of platelet-derived growth factor A-chain.
AB  - Platelet-derived growth factor (PDGF) A-chain is found in two different splice
      variants; the long A-chain variant differs from the short one in that it contains
      a stretch of basic amino acid residues in the C-terminal part that mediates
      retention of the growth factor inside the producer cell and to the cell matrix.
      By analyzing mutants in which different amino acid residues in the retention
      motif had been changed to alanine residues, we found that the total positive
      charge of the sequence is of importance for the function of the retention motif.
      Moreover, we showed that retention also occurs if only one of the polypeptides in
      the PDGF dimer carries the retention motif. Surface iodination and competition
      with a peptide having the sequence of the retention motif revealed that the long
      A-chain variant, in contrast to the short A-chain variant, is localized on the
      outside of the cells and is also associated to the cell matrix. The association
      is likely to be mediated partially through heparan sulfate proteoglycans since
      treatment of matrix with heparitinase released the long A-chain variant.

PMID- 8288646
TI  - Specific heparan sulfate saccharides mediate the activity of basic fibroblast
      growth factor.
AB  - In a previous study, we showed that heparitinase releases a 14-saccharide
      sequence (Oligo-H) from heparan sulfate (HS) with the structure delta GlcUA beta
      1,4GlcNSO3-alpha 1,4[IdceA(2S)alpha 1,4GlcNSO3]5 alpha 1,4IdceA alpha 1,4GlcNAc
      (where IdceA(2S) represents iduronic acid 2-sulfate), which binds to basic
      fibroblast growth factor (bFGF) with high affinity (Turnbull, J. E., Fernig, D.,
      Ke, Y., Wilkinson, M. C. & Gallagher, J. T. (1992) J. Biol. Chem. 267, 10337
      10341). This paper describes further work on the binding properties of HS
      saccharides and their capacity to mediate bFGF activity in a mitogenesis assay in
      which responsiveness is dependent on the addition of HS or heparin. Saccharides
      prepared by heparinase or nitrous acid digestion and heparitinase-resistant
      fragments five disaccharide units (degree of polymerization (dp) = 10) or less in
      size were unable to activate bFGF. However, heparitinase-resistant saccharides of
      dp12-16 were active in the assay; the dp14 and dp16 fractions were equivalent in
      activity to heparin and more active than the parent HS. Saccharides of the same
      size and basic structure as the active fractions (> or = dp12) bound to bFGF with
      high relative affinity. Active saccharides were composed mainly of N-sulfated
      disaccharides, the predominant unit being IdceA(2S)-GlcNSO3. This was enriched at
      least 5-fold in the active saccharides by comparison with the original HS. In
      addition, the dp12 and dp14 active fractions had a notably low content of
      trisulfated disaccharides (IdceA(2S)-GlcNSO3(6S)) (where GlcNSO3(6S) represents N
      sulfated glucosamine 6-sulfate), which are the major repeat units of heparin. The
      data show that sequences similar in size and basic structure to Oligo-H can
      mediate the mitogenic activity of bFGF. Overall, the results provide further
      evidence that specific HS sequences are generated biosynthetically in order to
      fulfill particular biological functions such as activation of bFGF.

PMID- 8288647
TI  - Purified yeast RNA polymerase II reads through intrinsic blocks to elongation in
      response to the yeast TFIIS analogue, P37.
AB  - Saccharomyces cerevisiae has a TFIIS-related transcription elongation factor,
      originally called P37 (Sawadogo, M., Sentenac, A., and Fromageot, P. (1979) J.
      Biol. Chem. 255, 12-15; Nakanishi, T., Nakano, A., Nomura, K., Sekimizu, K., and
      Natori, S. (1992) J. Biol. Chem. 267, 13200-13204), which binds directly to RNA
      polymerase II and stimulates read-through of intrinsic blocks to elongation. To
      elucidate functional features of this protein:protein interaction, we tested the
      ability of several forms of RNA polymerase II to respond to either full-length or
      an amino-terminal truncation of TFIIS. The variants of the polymerase differed in
      the structure of the carboxyl-terminal domain of the largest subunit or lacked
      two of the smaller subunits. No differences in ability to recognize intrinsic
      blocks to elongation or to read through them in response to either form of TFIIS
      were detected among these variants. Furthermore, ternary complexes containing
      each variant form of RNA polymerase cleave the 3' end of the nascent transcripts
      in response to TFIIS, a reaction previously reported for mammalian and Drosophila
      TFIIS (Kassavetis, G. A., and Geiduschek, E. P. (1993) Science 259, 944-945) and
      likely to be important in TFIIS function. Thus the carboxyl-terminal domain of
      the largest subunit and subunits four and seven of the polymerase, required in
      vivo, are not required in vitro for recognition of intrinsic blocks to
      elongation, read-through in response to TFIIS, or TFIIS-stimulated cleavage of
      the nascent transcript.

PMID- 8288648
TI  - Molecular mechanism of the synergistic phosphorylation of phosphatase inhibitor
      2. Cloning, expression, and site-directed mutagenesis of inhibitor-2.
AB  - Inhibitor-2 (I-2) is the regulatory subunit of the ATP-Mg-dependent phosphatase,
      a cytosolic form of type 1 protein phosphatase. Phosphorylation of I-2 at Thr-72
      by the protein kinase glycogen synthase kinase-3 (GSK-3) leads to activation of
      the enzyme. Casein kinase II action was shown to synergistically enhance
      phosphorylation and activation by GSK-3 (DePaoli-Roach, A.A. (1984) J. Biol.
      Chem. 259, 12144-12152). Rabbit skeletal muscle and liver I-2 cDNA clones have
      been isolated. Rabbit skeletal muscle cDNAs could be placed in two subtypes,
      differing in the length of the 3'-untranslated region. The coding sequence of 612
      nucleotides was identical in the two skeletal muscle and the liver cDNAs and
      predicted a protein of 204 amino acids, consistent with analysis of the purified
      protein. Northern hybridization analysis indicated that the two mRNAs of 1.7 and
      2.7 kilobase pairs were present in all rabbit tissues examined, except in liver,
      where only the larger transcript was detected, and in testis, where additional
      transcripts were present. Expression in Escherichia coli of wild-type and
      phosphorylation site mutants resulted in the production of I-2 polypeptides with
      apparent M(r) values of approximately 31,000 on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The inhibitory activity of the recombinant
      proteins was similar to that of native rabbit skeletal muscle I-2 and was
      unaffected by the substitution of alanine for the GSK-3 site (Thr-72) and for the
      casein kinase II sites (Ser-86 and Ser-120/121) or by substitution of glutamic
      acid and aspartic acid for Thr-72 and Ser-86. Recombinant wild-type I-2 and the
      Ala-120/121 mutant were phosphorylated synergistically by GSK-3 and casein kinase
      II. The Thr-72 and Ser-86 mutants, however, did not undergo this synergistic
      phosphorylation. Our studies indicate that Thr-72 is the only GSK-3 site and that
      Ser-86 is the casein kinase II site required for the potentiation of GSK-3
      action. Furthermore, acidic residues cannot substitute for the phosphate group
      either in enhancing GSK-3 phosphorylation or in activating the phosphatase.

PMID- 8288650
TI  - Metabolic processing of cyclobutyl pyrimidine dimers and (6-4) photoproducts in
      UV-treated human cells. Evidence for distinct excision-repair pathways.
AB  - A new nuclease digestion assay was developed to elucidate the human excision
      repair system operating on cyclobutyl pyrimidine dimers and (6-4) photoproducts.
      We analyzed lesions that accumulated in excised oligonucleotide fragments during
      incubation of UV-treated cultured fibroblasts. (6-4) photoproducts were removed
      intact, whereas excised cyclobutyl dimers often contained ruptured
      interpyrimidine phosphodiester bonds, raising the possibility that the intradimer
      backbone-cleavage reaction may help promote the bypass of unexcised dimers by the
      DNA replication or RNA transcription machinery. Cell strains representing eight
      different inherited forms of the cancer-prone skin disease xeroderma pigmentosum
      (XP) were generally found to exhibit characteristic abilities to excise the two
      classes of photolesions, ranging from total deficiency in groups A and G to
      normal proficiency in the variant. The capacity of any given XP group to act on
      one class of photoproducts in no way predicted its ability to act on the other.
      Finally, in those XP strains displaying significant levels of dimer removal, the
      ratio of intact-versus-modified dimers was normal, implying that rupture of the
      intradimer backbone linkage occurs independently of subsequent excision-repair
      reactions. Our data indicate that cyclobutyl dimers and (6-4) photoproducts are
      processed by distinct nucleotide-excision-repair pathways in human cells.

PMID- 8288649
TI  - Noncontiguous domains of the alpha-factor receptor of yeasts confer ligand
      specificity.
AB  - The Saccharomyces cerevisiae alpha-factor receptor has a 3400-fold higher
      affinity for the S. cerevisiae alpha-factor peptide (c-alpha-f) than for the
      Saccharomyces kluyveri alpha-factor peptide (k-alpha-f) as determined by
      competition for [3H] c-alpha-f binding. The S. kluyveri alpha-factor receptor has
      an approximately 2-fold higher affinity for k-alpha-f than for c-alpha-f. The S.
      kluyveri receptor gene (k-STE2) is incompletely regulated by S. cerevisiae mating
      type and poorly expressed on the surface of an S. cerevisiae mating type a
      strain. A chimeric receptor (c/k1) with amino acid residues 1-45 derived from S.
      cerevisiae and amino acid residues 46-427 from S. kluyveri exhibits the binding
      specificity of the S. kluyveri receptor. However, chimeric receptors containing
      residues 1-168 (c/k2) or 1-250 (c/k3) from S. cerevisiae and the remainder from
      the S. kluyveri receptor exhibit specificities similar to one another, but
      intermediate between the parent S. cerevisiae and S. kluyveri receptors. The
      relative ability of c-alpha-f and k-alpha-f to induce growth arrest in strains
      expressing chimeric receptors parallels relative affinity. Thus, two
      noncontiguous domains that include putative extracellular loops 1 and 3 and
      associated transmembrane segments, but exclude the extracellular NH2 terminus and
      loop 2, appear to contribute to alpha-factor receptor ligand specificity. COOH
      terminal regions of the S. kluyveri receptor appear to confer a desensitization
      defect when expressed in S. cerevisiae. The S. cerevisiae receptor truncated at
      residue 296 retains ligand specificity for growth arrest.

PMID- 8288651
TI  - Eighteen-level analysis of vertebral rotation following Harrington-Luque
      instrumentation in idiopathic scoliosis.
AB  - We used the Perdriolle method to measure the rotation of each vertebra from the
      seventh cervical to the fifth lumbar level, before and after posterior spinal
      arthrodesis and Harrington-Luque instrumentation in fifteen patients who had
      idiopathic scoliosis. The primary curve was corrected an average of 50 per cent
      and the secondary curve, an average of 73 per cent. Following the operation, the
      average number of vertebrae involved in the primary curve increased from seven
      (range, five to ten) to nine (range, seven to fifteen). The rotation of the
      apical vertebra of the primary curve increased 10 degrees in four patients and 5
      degrees in two patients and decreased 5 degrees in one patient. The rotation of
      the apical vertebra of the secondary curve increased 10 degrees in three patients
      and 5 degrees in one patient and decreased 5 degrees in four patients. In seven
      patients, correction of the curve was associated with unexpected counter
      rotation, beyond the levels of instrumentation, of three or more vertebral
      segments that had been in neutral position before the operation.

PMID- 8288652
TI  - Intergranular corrosion-fatigue failure of cobalt-alloy femoral stems. A failure
      analysis of two implants.
AB  - Two modular hip implants with a cobalt-alloy head and a cobalt-alloy stem were
      retrieved after a fracture had occurred in the neck region of the femoral
      component, eighty-five and seventy months after implantation. Both implants
      failed less than one millimeter distal to the taper junction between the head and
      the stem (outside of the taper). The fracture surfaces of the implant were
      investigated with the use of scanning electron microscopy, to determine the
      nature of the failure process. The fractures occurred at the grain boundaries of
      the microstructure and appeared to be the result of three factors: porosity at
      the grain boundaries; intergranular corrosive attack, initiated both at the head
      neck taper and at the free surface; and cyclic fatigue-loading of the stem. The
      corrosive attack of the free surface was initiated, in part, by the egression of
      surface grains and by the ingression of fluid into the intergranular regions.
      Sectioned surfaces showed extensive intergranular corrosive attack in the
      prosthetic neck localized in the region of the head-neck taper junction and
      penetrating deeply into the microstructure.

PMID- 8288653
TI  - Tarsal tunnel syndrome caused by an unrecognized fracture of the posterior
      process of the talus (Cedell fracture). A case report.

PMID- 8288654
TI  - Hodgkin disease of the spine presenting as alcohol-related pain. A case report
      and review of the literature.

PMID- 8288655
TI  - Open physeal fractures of the distal phalanx of the great toe. A case report.

PMID- 8288656
TI  - Acute gouty arthropathy after total knee arthroplasty. A case report.

PMID- 8288657
TI  - Intracapsular fractures of the hip.

PMID- 8288658
TI  - Outcomes after displaced fractures of the femoral neck. A meta-analysis of one
      hundred and six published reports.
AB  - Methods of meta-analysis, a technique for the combination of data from multiple
      sources, were applied to analyze 106 reports of the treatment of displaced
      fractures of the femoral neck. Two years or less after primary internal fixation
      of a displaced fracture of the femoral neck, a non-union had developed in 33 per
      cent of the patients and avascular necrosis, in 16 per cent. The rate of
      performance of a second operation within two years ranged from 20 to 36 per cent
      after internal fixation and from 6 to 18 per cent after hemiarthroplasty
      (relative risk, 2.6; 95 per cent confidence interval, 1.4 to 4.6). Conversion to
      an arthroplasty was the most common reoperation after internal fixation and
      accounted for about two-thirds of these procedures. The remaining one-third of
      the reoperations were for removal of the implant or revision of the internal
      fixation. For the patients who had had a hemiarthroplasty, the most common
      reoperations were conversion to a total hip replacement, removal or revision of
      the prosthesis, and debridement of the wound. Although we observed an increase in
      the rate of mortality at thirty days after primary hemiarthroplasty compared with
      that after primary internal fixation, the difference was not significant (p =
      0.22) and did not persist beyond three months. The absolute difference in
      perioperative mortality between the two groups was small. An anterior operative
      approach for arthroplasty consistently was associated with a lower rate of
      mortality at two months than was a posterior approach. Some reports showed
      promising results after total hip replacement for displaced fractures of the
      femoral neck; however, randomized clinical trials are still needed to establish
      the value of this treatment.

PMID- 8288659
TI  - Changes in residual volume relative to vital capacity and total lung capacity
      after arthrodesis of the spine in patients who have adolescent idiopathic
      scoliosis.

PMID- 8288660
TI  - Early failure of short-segment pedicle instrumentation for thoracolumbar
      fractures. A preliminary report.

PMID- 8288661
TI  - Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed
      ultrasound.
AB  - Sixty-seven closed or grade-I open fractures of the tibial shaft were examined in
      a prospective, randomized, double-blind evaluation of use of a new ultrasound
      stimulating device as an adjunct to conventional treatment with a cast. Thirty
      three fractures were treated with the active device and thirty-four, with a
      placebo control device. At the end of the treatment, there was a statistically
      significant decrease in the time to clinical healing (86 +/- 5.8 days in the
      active-treatment group compared with 114 +/- 10.4 days in the control group) (p =
      0.01) and also a significant decrease in the time to over-all (clinical and
      radiographic) healing (96 +/- 4.9 days in the active-treatment group compared
      with 154 +/- 13.7 days in the control group) (p = 0.0001). The patients'
      compliance with the use of the device was excellent, and there were no serious
      complications related to its use. This study confirms earlier animal and clinical
      studies that demonstrated the efficacy of low-intensity ultrasound stimulation in
      the acceleration of the normal fracture-repair process.

PMID- 8288662
TI  - Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for
      the prevention of deep venous thrombosis after elective hip replacement. A
      clinical trial comparing efficacy and safety. Enoxaparin Clinical Trial Group.
AB  - A randomized, parallel-group, open-label clinical trial (the physicians,
      patients, and staff were not blinded with regard to the regimen that had been
      used) was conducted, between December 1988 and September 1990, to compare the
      safety and efficacy of enoxaparin, a low-molecular-weight heparin, with the
      safety and efficacy of unfractionated heparin for the prevention of deep venous
      thrombosis after elective hip replacement. Six hundred and ten patients were
      randomized, and 607 patients received one of the study medications. The
      evaluations of efficacy included contrast-media venography, non-invasive vascular
      examination, and clinical examination. Data on efficacy were available for 604
      patients, who had been assigned to one of three treatment groups: thirty
      milligrams of enoxaparin every twelve hours (194 patients), forty milligrams of
      enoxaparin once daily (203 patients), or 5000 units of unfractionated heparin
      every eight hours (207 patients). All drugs were administered subcutaneously.
      Dosages were not adjusted on the basis of the results of coagulation tests or the
      body weight of the patient. Treatment was initiated within twenty-four hours
      after the operation and continued for a maximum of seven days. The primary safety
      outcome was the occurrence of bleeding episodes. An intent-to-treat patient
      analysis revealed that deep venous thrombosis occurred in nine (5 per cent) of
      the 194 patients who received thirty milligrams of enoxaparin every twelve hours,
      thirty (15 per cent) of the 203 patients who received forty milligrams of
      enoxaparin once daily, and twenty-four (12 per cent) of the 207 patients who
      received unfractionated heparin. The rate of deep venous thrombosis was
      significantly lower in the group that received thirty milligrams of enoxaparin
      every twelve hours than in the group that received unfractionated heparin (p =
      0.03) and in the group that received forty milligrams of enoxaparin once daily (p
      = 0.0002). No clinically symptomatic pulmonary embolism was observed during the
      treatment or follow-up phase of this study in the group that received thirty
      milligrams of enoxaparin every twelve hours. Analysis of evaluable patients
      revealed a marked reduction in the rate of deep venous thrombosis in the group
      that received thirty milligrams of enoxaparin every twelve hours (eight [6 per
      cent] of 136 patients) compared with the group that received heparin (twenty-one
      [15 per cent] of 145 patients) (p = 0.10); however, this difference was not
      significant because of the small number of patients included in this
      analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8288663
TI  - Closed wound drainage in total hip or total knee replacement. A prospective,
      randomized study.
AB  - We prospectively randomized 415 total joint replacements for either a closed
      wound-drainage system or no postoperative drainage. Drainage was not used in 200
      total joint replacements, of which 138 were total knee replacements and sixty
      two, total hip replacements. Drainage was used in 215 total joint replacements,
      of which 137 were total knee replacements and seventy-eight, total hip
      replacements. All patients were evaluated for the presence of excessive
      postoperative drainage that necessitated cessation of the range-of-motion
      exercises, the amount of transfused blood (homologous and autologous), and the
      preoperative and postoperative hemoglobin levels. The range of motion was
      assessed daily in the patients who had a total knee replacement. No statistical
      difference was found in the number of patients who had excessive postoperative
      drainage from a drained or non-drained wound. There was also no statistical
      difference with respect to the amount of transfused blood and the preoperative
      and postoperative hemoglobin levels. Furthermore, in the patients who had a total
      knee replacement, there were no statistical differences between drained and non
      drained wounds with respect to the daily range of motion during the first seven
      days postoperatively. The mean amount of blood transfused was 157 milliliters in
      the total knee replacements with drains, 160 milliliters in the total knee
      replacements without drains, 188 milliliters in the total hip replacements with
      drains, and ninety-three milliliters in the total hip replacements without
      drains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288665
TI  - Cuneiform osteotomy of the femoral neck in the treatment of slipped capital
      femoral epiphysis. A follow-up note.
AB  - The long-term clinical and roentgenographic results of cuneiform osteotomy of the
      femoral neck at the level of the physis in sixty-one patients (sixty-six hips)
      who had a slipped capital femoral epiphysis of more than 30 degrees were
      reviewed. The result was excellent in fifty-five hips, good in six hips, fair in
      two hips, and poor in three hips. The results in thirty-eight of these hips were
      reported in 1984. Osteoarthrosis developed in six patients; it was mild in four
      patients, moderate in one, and severe in one. Two patients had evidence of
      chondrolysis. The pin was found to have penetrated into the joint in all six of
      the patients who had osteoarthrosis and in one patient who had chondrolysis.
      Complete avascular necrosis of the femoral head developed in two patients and
      segmental avascular necrosis in one; all three patients had an acute-on-chronic
      slip.

PMID- 8288664
TI  - Prophylaxis against infection in total joint arthroplasty. One day of cefuroxime
      compared with three days of cefazolin.
AB  - The efficacy of cefuroxime was compared with the efficacy of cefazolin for
      prophylaxis against postoperative wound infection in a prospective, double-blind,
      multicenter study of 1354 patients who had had elective primary or revision total
      hip or knee arthroplasty. The patients were randomly assigned to receive either
      1.5 grams of cefuroxime followed by 750 milligrams eight and sixteen hours later
      (for a total of one day of antibiotic treatment), or one gram of cefazolin every
      eight hours for nine doses (for a total of three days of antibiotic treatment).
      The first dose of each drug was administered fifteen to sixty minutes before the
      operative incision was made (for a primary operation) or after tissue samples had
      been obtained for culture (for a revision procedure). After the operation, the
      patients were assessed daily while hospitalized and then at two to three months
      and one year after the operation. Demographic characteristics and risk factors
      were similar in the two groups. For the patients who had had a primary hip
      arthroplasty, the rate of deep wound infection was 0.5 per cent (one of 187) for
      those who had received cefuroxime and 1.2 per cent (two of 168) for those who had
      received cefazolin. For the patients who had had a primary knee arthroplasty, the
      rate of deep wound infection was 0.6 per cent (one of 178) for those who had
      received cefuroxime and 1.4 per cent (three of 207) for those who had received
      cefazolin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288666
TI  - Radiolucency at the bone-cement interface in total knee replacement. The effects
      of bone-surface preparation and cement technique.
AB  - Three hundred and sixty-three knees (221 patients) that had been treated with
      total arthroplasty between 1975 and 1985 were divided into three groups on the
      basis of the preparation of the surface of the bone and the technique of the
      cement application. Group 1 (155 knees) was treated with irrigation of the bone
      surfaces with a syringe and manual packing of the bone cement. Group 2 (sixty-one
      knees) had high-volume, high-pressure lavage of the bone surfaces and manual
      packing of the cement. Group 3 (147 knees) had high-volume, high-pressure lavage
      and pressure injection of low-viscosity methylmethacrylate cement. Radiolucency
      was evaluated at each follow-up interval, and the findings were subjected to chi
      square analysis and Kaplan-Meier survival analysis. Chi-square analysis of the
      data at one and three years indicated a significantly higher frequency of lines
      at the bone-cement interface in the femur and tibia in Group-1 knees compared
      with those in Groups 2 and 3. The survival curves showed increasing rates of
      radiolucency adjacent to the tibial components of the knees that had been
      prepared with lavage that was not high-volume and high-pressure and that had been
      prepared with finger-packing of cement (Group 1). This may partially explain the
      clinical problem of loosening of tibial components despite acceptable alignment.
      This study demonstrates that proper preparation of the cancellous bone and
      pressurization of the cement reduce the initial occurrence of a radiolucent line,
      which may have a positive effect on the ultimate failure of at least the tibial
      component.

PMID- 8288667
TI  - Distal loss of femoral bone following total knee arthroplasty. Measurement with
      visual and computer-processing of roentgenograms and dual-energy x-ray
      absorptiometry.
AB  - The changes in bone-mineral content in the distal aspect of a cadaveric femur
      that had been prepared for insertion of the femoral component of a total condylar
      knee prosthesis were evaluated with visual inspection and computer-processing of
      roentgenograms and with dual-energy x-ray absorptiometry. Seventeen small slices
      of bone, each three millimeters wide, were removed so that, finally, 89 per cent
      of the bone was lost from the distal femoral metaphysis. Standardized lateral
      roentgenograms of the specimen were made with use of a reference step-wedge of
      hydroxyapatite, and dual-energy x-ray absorptiometry studies were performed with
      the x-ray beam tangential to the interface. The roentgenograms were digitized and
      the bone mineral was measured with use of computer analysis. Dual-energy x-ray
      absorptiometry was performed with and without the femoral prosthesis in place, in
      order to determine the effect of the metallic prosthesis on the accuracy of the
      measurement. A bone loss of 25 per cent or more was identified visually by all
      five of the readers 100 per cent of the time; losses of 20 to 24 per cent, 15 to
      19 per cent, 10 to 14 per cent, and 3 to 9 per cent were correctly identified 92,
      75, 66, and 59 per cent of the time, respectively. The measurements of bone
      mineral content that were obtained from the digitized roentgenograms were
      linearly correlated with the actual bone-mineral content (the ash content) (r =
      0.97, p < 0.001) and were three times more accurate than the visual readings. The
      determinations of bone-mineral content with dual-energy x-ray absorptiometry
      correlated highly with the ash content (r = 1.00, p < 0.001) and were seven times
      more accurate than the visual readings. There was only a 4 per cent difference
      between the measurements with dual-energy x-ray absorptiometry made with the
      prosthesis in place and those made without it in place (p < 0.01). Dual-energy x
      ray absorptiometry was the most accurate of the three methods and could detect
      the smallest experimentally created loss; computer-processing and visual
      processing of roentgenograms detected losses of 8 per cent or more and 25 per
      cent or more, respectively. Dual-energy x-ray absorptiometry and computer
      processing of the roentgenograms quantified the bone loss, while visual
      processing could detect only the presence or absence of bone loss.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8288668
TI  - The cement mantle in total hip arthroplasty. Analysis of long-term radiographic
      results.
AB  - The correlation between the thickness of the cement mantle, the medullary canal
      fill, and the orientation of the stem and the long-term radiographic outcome of
      836 cemented femoral components in patients who had a primary total hip
      replacement was assessed with use of survival analysis over a twenty-one-year
      follow-up period. The femoral stems of hips that had a two to five-millimeter
      thick cement mantle in the proximal medial region had a better outcome than stems
      implanted with a thicker or thinner cement mantle. Stems in femora with less than
      two millimeters of proximal medial cancellous bone had a better outcome than
      stems in femora with thicker cancellous bone. Stems that filled more than half of
      the medullary canal had better radiographic results than those that filled half
      or less. Progressive loosening, fracture of the cement, and radiolucent lines at
      the stem-cement or bone-cement interfaces were more likely to develop in stems
      that were oriented in more than 5 degrees of varus than in those in neutral or
      valgus. The noted correlations were true whether the stem was made of titanium
      alloy or of stainless steel. The results of this study emphasize the importance
      of careful preoperative planning in total hip arthroplasty done with cement and
      provide guidelines for the selection of the shape, size, and position of the
      stem.

PMID- 8288669
TI  - An alternative method for determination of the carpal height ratio.
AB  - Radiographs of the wrist often do not include the entire third metacarpal, so the
      standard method for measurement of the carpal height ratio (the carpal height
      divided by the length of the third metacarpal) cannot be used. In this study, the
      ratio of the carpal height relative to the length of the capitate was evaluated
      for its suitability as a reproducible alternative. The revised carpal height
      ratio (the carpal height divided by the capitate length) was evaluated for
      reproducibility and clinical utility in both in vitro and in vivo studies: it was
      determined from the radiographs of ten cadaveric wrists; those of 100 wrists
      (fifty pairs) of normal volunteers, made with controlled positioning; those of
      100 wrists, drawn at random from radiographs that had been previously interpreted
      as showing normal findings; and those of fifty wrists of twenty-nine patients who
      had documented rheumatoid arthritis. The new ratio was found to be constant in
      the normal population, consistent bilaterally, decreased in patients who had
      carpal collapse, and reproducible.

PMID- 8288670
TI  - Relative motion of hip stems under load. An in vitro study of symmetrical,
      asymmetrical, and custom asymmetrical designs.
AB  - Symmetrical, asymmetrical, and custom asymmetrical stems without collars were
      manufactured and inserted without cement, in that order, into each of eight
      femora. Displacement transducers were mounted at different locations to measure
      relative motion between the stem and the bone. A load was applied to simulate the
      forces acting on a hip joint in a single-limb stance. A force of 1000 newtons was
      applied three times in order to seat the prosthesis, and then a cyclical force of
      1000 newtons was applied to the head of the prosthesis; readings of relative
      motion were taken every 500 cycles, until 2500 cycles had been reached. The
      relative motion diminished as the number of cycles increased, with most of the
      reduction occurring within the first 500 cycles. The symmetrical stem had the
      least relative axial motion, with an average of six micrometers, but the other
      stems also had low values: eleven micrometers for the custom stem, and nineteen
      micrometers for the asymmetrical stem. In terms of axial rotation, however, the
      symmetrical stem had several times more motion than did the other two stems.
      Motion of the stem tip toward or away from the canal in the frontal plane and in
      the sagittal plane also was higher for the symmetrical stem. Axial migration
      (permanent sinkage after 2500 cycles) was very similar between all three types of
      stem. In a torsional loading test, the symmetrical stem showed about ten times
      more relative rotational motion than did the other two stems. Over-all, the
      custom stem and the asymmetrical stem had similar results.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8288671
TI  - Pharmaceutical advertising and the cost of medical care.

PMID- 8288672
TI  - Understanding the biology of cancer: has this any impact on treatment?
AB  - Rapid advances in laboratory techniques in the last two decades and, what is more
      important, in the last 5-7 years have significantly increased our knowledge and
      understanding on many fronts. We have learned much about (a) the basic biological
      processes of growth control and its aberrations, (b) the possible mechanisms
      involved in genetic initiation, progression and suppression, (c) the complexity
      of the multistep carcinogenesis induced by viruses, chemicals, hormones and other
      iatrogenic factors, (d) the secrets of immunological defence mechanisms and a
      host of other fundamental processes, (e) the application of molecular biology
      techniques to clinical problems, etc. The list is unending and often leads the
      uninitiated clinician to believe that the resolution of the mystery of the cancer
      cell and its successful control and cure are almost at hand. He or she often
      comes to believe that conventional principles in cancer treatment have radically
      changed from the 1960 and 1970 and that a new era in cancer treatment, based on
      our recent biological understanding, has already arrived. There is little doubt
      that the treatment scenario has changed significantly and that there is more hope
      for a cancer patient today than ever before-especially in certain types of
      paediatric and lymphoproliferative disorders; however, the unfortunate fact is
      that this cautiously optimistic therapeutic scenario has come about not because
      of any great understanding of the biological processes, which continue to
      confound us, but because of the intense interaction of various therapeutic
      disciplines and sophisticated technology now available for early diagnosis and
      more efficient therapeutic procedures in radiotherapy, chemotherapy and surgery.
      The author presents evidence and data here to show that, while treatment results
      have improved, we have a long way to go in understanding the biological processes
      before our knowledge can have a significant impact on the overall treatment
      methods in current use. The principles of cancer treatment, though modified have
      not changed. In fact, in the light of our current knowledge, they have been re
      emphasized.

PMID- 8288673
TI  - Transplacental carcinogenicity of low doses of 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone administered subcutaneously or intratracheally to hamsters.
AB  - Our previous studies have demonstrated that doses of 300-50 mg/kg 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) injected subcutaneously into
      pregnant hamsters cause a 44% incidence of respiratory-tract tumors in the
      offspring. In this study, we have extended the assay of the carcinogenic potency
      of NNK to doses ranging from 50 mg to 0.05 mg/kg body weight and to a second
      route of administration, intratracheal instillation, which is more relevant to
      inhalation of tobacco smoke by pregnant women. Among the offspring whose mothers
      had been injected subcutaneously with NNK (20-1 mg/kg), the total tumor incidence
      (57.2%-16.7%) decreased with decreasing dose levels. After intratracheal
      instillation of 50-0.05 mg/kg NNK the overall incidence varied from 28.6% to 50%
      but no dose response was observed. The main target organs were the adrenal glands
      (Phaechromocytomas) and nasal cavities (adenocarcinomas of the olfactory region).
      A low incidence of ductular adenomas of the pancreas was observed with low doses
      of NNK instilled intratracheally. These results demonstrate that NNK, at doses
      that are comparable to the cumulative exposure during a 9-month period in women,
      is a potent transplacental carcinogen in hamsters.

PMID- 8288674
TI  - The antiemetic activity of granisetron against cytostatic-treatment-induced
      emesis in 10- to 13-week-old ferrets.
AB  - The antiemetic activity of granisetron was examined in ferrets aged 10-13 weeks.
      Emesis was induced by exposure to either whole-body X-irradiation (50 Gy over
      10.4 min) or cyclophosphamide (80 mg/kg i.v.) plus doxorubicin (6 mg/kg i.v.).
      Following exposure to whole-body X-irradiation, the young ferrets vomited with a
      similar latency to vomit and severity of emesis to that shown by adult animals.
      Granisetron (0.5 mg/kg i.v.) significantly reduced (P < or = 0.05) the number of
      vomits and retches and two out of four animals were completely protected.
      Following injection of cyclophosphamide and doxorubicin, the young ferrets showed
      a reduced emetic response compared to adult animals. Following a dose of
      granisetron (0.5 mg/kg i.v.), only one out of four ferrets vomited compared to
      four out of four in the control group. Further experiments showed that cisplatin
      (12.5 mg/kg i.v.) was unable to induce vomiting in the young ferret (n = 2).
      Granisetron (0.5 mg/kg i.v.) was well tolerated by the young ferret and was able
      to reduce significantly or completely abolish emesis induced by cytostatic
      treatment. The data support the use of granisetron in pediatric patients and
      clinical trials are currently underway in this patient population.

PMID- 8288675
TI  - Increase of labeling indices in gastrointestinal mucosae of mice and rats by
      compounds of the okadaic acid type.
AB  - Effects of compounds of the okadaic acid type (okadaic acid, dinophysistoxin-1,
      calyculin A and tautomycin) on proliferation by digestive-tract epithelial cells
      were investigated in mice and rats. In mice, a single oral administration of
      these agents caused significant enhancement of BrdU labeling indices in a
      dose/response manner. Exceptions showing no response were limited to the pyloric
      mucosa for okadaic acid, the pyloric and fundic mucosa for calyculin A and the
      pyloric mucosa for tautomycin. Sequential analysis of labeling indices after a
      single oral administration of dinophysistoxin-1 revealed two peaks of cell
      proliferation at 18 h and 36 h in the esophagus, ileum and colon. The labeling
      indices of the forestomach, fundus, pylorus and jejunum, on the other hand,
      continuously increased from 6 h after the administration. Elevated proliferation
      was also observed in the skin after 30 h or after, but no effects on the liver or
      kidney were evident. A single oral administration of the okadaic acid type of
      compounds also dose-dependently enhanced cell proliferation of the rat digestive
      tract. These results strongly suggest that the okadaic acid class of compounds
      may exert promoting potential for the gastrointestinal mucosa when administered
      orally.

PMID- 8288676
TI  - Inhaled interleukin-2 in combination with low-dose systemic interleukin-2 and
      interferon alpha in patients with pulmonary metastatic renal-cell carcinoma:
      effectiveness and toxicity of mainly local treatment.
AB  - We describe here a mainly topical interleukin-2 (IL-2) application in pulmonary
      metastatic renal-cell carcinoma: a high-dose long-term inhalation of IL-2 (90% of
      IL-2 dose) and low-dose systemic subcutaneous IL-2 (10% of IL-2 dose) and
      systemic subcutaneous interferon alpha (IFN alpha). The effectiveness of this
      treatment is remarkable. No pulmonary metastases progressed during treatment. One
      complete response, 8 partial responses, and 6 cases of stable disease were
      achieved in the lungs of the 15 patients. In addition, 3 of 7 patients had
      partial responses and 1 of 7 had stabilization of non-pulmonary metastases.
      Overall response according to WHO criteria was 1 complete response, 6 partial
      responses, 2 mixed responses, 5 stable diseases and 1 progressive disease.
      Toxicity was low. Only WHO grade I toxicity occurred, except for a single grade
      II event (bronchospasm). This allowed long-term ambulatory treatment (1-23
      months) inclusion of high-risk patients, and inclusion of patients with advanced
      disease. The expected mean survival of patients was 9.9 months, the actual mean
      survival is now 19.1 months, and 11 of 15 patients are still alive. Quality of
      life during treatment was good. Inhalation of IL-2 serves as a clinical model for
      high effectiveness and low toxicity of long-term local IL-2 application. We
      conclude that mainly local treatment might be the key to successful nontoxic use
      of IL-2 in cancer patients.

PMID- 8288678
TI  - Fourth biennial meeting of the International Gynecologic Cancer Society,
      Stockholm 1993.

PMID- 8288677
TI  - The relevance of flow-cytometric DNA content in the evaluation of lung cancer.
AB  - Cells from a group of 185 patients suffering from malignant tumours (160 non
      small-cell lung carcinoma, 13 small-cell lung carcinoma, and 12 non-epithelial
      tumours) and 6 with benign lung tumours were studied by flow cytometry in order
      to detect the prognostic value of DNA content. A total of 144 (90%) non-small
      cell lung carcinomas (NSCLC) and 8 (62%) small-cell lung carcinomas (SCLC)
      exhibited aneuploidy. Furthermore 52% (83 patients) NSCLC, 24% (3 patients) SCLC
      and 50% (6 patients) non-epithelial tumours demonstrated multiclonality. Benign
      cases showed diploid DNA content. For actuarial survival analysis using the
      Bergesson and Gage method and the Greenwood variance, 142 patients were selected.
      Statistical comparisons were made by the use of the t-test for unpaired data
      between fixed times. No correlation was observed between ploidy and stage,
      histological grading or treatment modality. A statistically significantly better
      survival was observed after 12, 18 and 24 months of follow-up for diploid and
      monoclonal (with the exclusion of hypo- and hypertetraploid) patients. Thus, flow
      cytometric DNA analysis may be useful in prognostic assessment of human lung
      tumours.

PMID- 8288679
TI  - 7th international symposium of the Division of Experimental Cancer Research (AEK)
      of the German Cancer Society, 24-26 March 1993, Heidelberg, (Germany): free
      communications of the biochemistry branch.

PMID- 8288680
TI  - Detection of MDM2-proto-oncogene in paraffin embedded human bronchial epithelium.
AB  - Recently a new proto-oncogene, the murine double-minute 2 (MDM2), has been
      described. MDM2 becomes oncogenic due to amplification and overexpression. Among
      other proto-oncogenes MDM2 becomes interesting since MDM2 protein can associate
      with both mutant and wild type p53 tumor suppressor gene products and thus
      inhibit p53-mediated transactivation of other genes. Loss of p53 tumor suppressor
      function is the most frequently observed alteration in human tumors.
      Immunohistochemical studies investigating the quantity of MDM2 protein in human
      sarcomas revealed an overexpression in 30% of the specimens. Here we describe the
      successful use of a monoclonal antibody (IF2) for the detection of MDM2 protein
      in paraffin-embedded tissue from human lung biopsies. 18 out of 44 specimens
      (41%), predominantly mucosal epithelial and glandular epithelial cells, stained
      positive for MDM2. No significant difference was observed between non
      cancerogenic cells adjacent to tumor cells and those specimens without any tumor
      cells but altered by inflammatory processes. In general, the staining pattern was
      restricted not to the nuclei, but to selected subnuclear compartments, probably
      representing the golgi apparatus or the endoplasmatic reticulum. Our data support
      the hypothesis that in addition to its nuclear function of forming a complex with
      p53, MDM2 may also be secreted and thus have a transcellular effect.

PMID- 8288681
TI  - Mandatory experience.

PMID- 8288682
TI  - SHEP vs. sense.

PMID- 8288683
TI  - Vitamin E and gynecomastia.

PMID- 8288684
TI  - Acute migratory arthritis: a diverse differential.

PMID- 8288685
TI  - Intestinal obstruction in a dialysis patient with a broken leg.

PMID- 8288686
TI  - Overwhelming pneumonia in a healthy young nursing assistant.

PMID- 8288687
TI  - Case in point. Wound botulism.

PMID- 8288688
TI  - Combination antiretroviral therapy for HIV infection.
AB  - Despite recent disappointment with antiretroviral agents, investigators continue
      to examine combination therapy with agents that target the same or different
      stages of the HIV life cycle. Initial studies suggest that when therapy is
      started early in the course of infection, certain combinations may be better than
      single-drug regimens in reducing viral burden and delaying the onset of drug
      resistance.

PMID- 8288689
TI  - Shock and pulmonary edema in an elderly woman.

PMID- 8288690
TI  - Distal renal tubular acidosis: molecular and clinical aspects.
AB  - The traditionally descriptive classification of DRTA disorders is being refined
      as molecular defects are identified. Diagnosis of DRTA is easy: Hyperchloremic
      acidosis should arouse suspicion, and confirmation can be obtained by measuring
      urinary pH and ammonia excretion. Treatment is also relatively straightforward
      and readily corrects all manifestations of the acidification defect.

PMID- 8288691
TI  - Blockbuster buster.

PMID- 8288692
TI  - The clinical science and art of Silas Weir Mitchell.

PMID- 8288693
TI  - Absence of p53 point mutations in parathyroid adenoma and carcinoma.
AB  - Primary hyperparathyroidism is a common disorder characterized by aberrant growth
      and function of solitary or multiple parathyroid glands. Many, if not all,
      parathyroid adenomas are examples of benign clonal neoplastic growth. The
      molecular events associated with the development of parathyroid neoplasia have
      not been well characterized. We examined benign and malignant parathyroid tissues
      for structural abnormalities of the p53 tumor suppressor gene. To screen for
      mutations in the p53 gene, we analyzed polymerase chain reaction-amplified DNA by
      denaturing gradient gel electrophoresis. DNA was isolated from 26 benign
      parathyroid adenomas and 3 parathyroid carcinomas, and polymerase chain reaction
      was used to amplify DNA fragments corresponding to the 4 evolutionarily conserved
      domains within exons 5, 7, and 8 of the p53 gene in which the majority of point
      mutations have been identified. Amplified DNA fragments were electrophoresed
      through polyacrylamide gels with linearly increasing gradients of the denaturants
      urea and formamide. After electrophoresis, the gels were examined for the
      presence of abnormally migrating bands, which represent DNA with altered melting
      points due to nucleotide sequence changes. Amplified fragments were of the
      expected size in DNA from 26 parathyroid adenomas and 3 parathyroid carcinomas.
      Denaturing gradient gel electrophoresis studies failed to disclose evidence of
      mutations in exons 5, 7, and 8 of the p53 gene in these neoplasms. We conclude
      that p53 point mutations do not appear to be a primary event responsible for
      neoplastic growth in parathyroid tissue.

PMID- 8288694
TI  - Genetic basis of endocrine disease. 6. Molecular basis of familial human growth
      hormone deficiency.

PMID- 8288695
TI  - Gonadotropin-releasing hormone antagonist for postpartum contraception: outcome
      for the mother and male offspring in the marmoset.
AB  - GnRH antagonists have potential for use in postpartum contraception, as it is
      likely that they would be effective in maintaining the inhibition of ovulation
      associated with lactation, but possible effects on the infant by transfer of
      antagonist via breast milk are unknown. The aim of this study was to establish
      whether chronic treatment with a GnRH antagonist would prevent ovulation
      throughout the period of lactation using the marmoset monkey as a model and to
      evaluate the effects of the presence of GnRH antagonist in breast milk on the
      postnatal rise in plasma testosterone concentrations in male infants. Mothers who
      had delivered male twins were selected. Starting within 3 days postpartum,
      mothers (n = 5/group) were treated with either 6.0 or 0.6 mg/kg of the GnRH
      antagonist antide, sc, once per week for 11 weeks. Ten postpartum lactating
      females acted as controls. All animals were housed in family groups with fertile
      males. To determine possible effects on the postnatal rise in testosterone,
      plasma samples were collected from the male infants of the high dose antide
      treated mothers at weekly intervals for 12 weeks. Plasma progesterone
      concentrations were monitored in lactating mothers until establishment of
      pregnancy in both treated and control groups. Concentrations of antide were
      determined by RIA in plasma from mothers in the high dose group, in their milk,
      and in pooled plasma samples from their infants. Ovulation followed by pregnancy
      occurred in all of the control animals. No ovulations occurred during treatment
      with antide. Antide was present throughout treatment in plasma and breast milk in
      the mother. In male infants feeding from mothers receiving high dose treatment,
      antide was not detectable in infant plasma, and plasma testosterone
      concentrations were within the normal range for male neonates in our colony.
      These results indicate that the GnRH antagonist has potential as a method of
      contraception postpartum without affecting the postnatal rise in testosterone in
      male infants.

PMID- 8288696
TI  - Physiological estrogen replacement may enhance the effectiveness of the
      gonadotropin-releasing hormone agonist in the treatment of hirsutism.
AB  - GnRH agonists (GnRH-A) have been used for the treatment of hirsutism in women
      with ovarian hyperandrogenism. However, significant side-effects, including
      vasomotor symptoms and bone loss, have prevented the long term use of this
      therapy. In this study, we evaluated the effects of low dose (physiological)
      estrogen replacement on the side-effects and clinical and hormonal parameters of
      22 hirsute women with ovarian hyperandrogenism when treated with a long-acting
      GnRH-A, Decapeptyl. Ten patients with Ferriman-Gallwey (FG) scores averaging 13.4
      +/- 1.5 were randomly assigned to be treated with Decapeptyl alone (3.75 mg, im,
      every 28 days for 6 months), and 12 other patients with FG scores averaging 13.3
      +/- 1 received Decapeptyl with estrogen (conjugated equine estrogens, 0.625 mg)
      for 21 days and medroxyprogesterone acetate (10 mg) for 10 days (days 12-21).
      After 6 months, LH was suppressed in both groups, whereas FSH was significantly
      reduced only in the group receiving GnRH-A with estrogen (2.5 +/- 4 vs. 4.8 +/-
      0.6 IU/L; P < 0.01). Serum androgen levels were reduced in both groups, although
      the reduction of testosterone and unbound testosterone was greater in the group
      receiving hormonal replacement [1.73 +/- 0.3 vs. 2.57 +/- 0.4 nmol/L for
      testosterone (P < 0.05); 8.3 +/- 1 vs. 14.6 +/- 2.8 pmol/L for unbound
      testosterone (P < 0.05)]. The reduction in hirsutism scores was greater with
      hormonal replacement (FG scores, -4.1 +/- 0.3 vs. -2.5 +/- 0.3; P < 0.05),
      whereas the polycystic appearance of ovaries by ultrasound was decreased in both
      groups. Amenorrhea and vasomotor symptoms were observed only with GnRH-A alone.
      Serum osteocalcin rose significantly with GnRH-A alone, reflecting a change in
      bone turnover (0.49 +/- 0.05 to 0.64 +/- 0.09 nmol/L; P < 0.05), but was
      unchanged with hormonal replacement. Patients receiving hormonal replacement had
      treatment extended to 1 yr. A further improvement of hirsutism, with scores
      dropping into the normal range (4.9 +/- 0.7), as well as a normalization of
      ovarian morphology were evident at this time. In conclusion, low dose
      (physiological) estrogen replacement may enhance the effects of GnRH-A treatment,
      while preventing most of the side-effects encountered with GnRH-A alone. This may
      allow more prolonged treatment, which is necessary for hirsutism.

PMID- 8288697
TI  - Dehydroepiandrosterone sulfate and anovulation increase serum inhibin and affect
      follicular function during administration of gonadotropins.
AB  - To test the hypothesis that testosterone (T) derived from circulating
      dehydroepiandrosterone sulfate (DS) or produced in excess within the anovulatory
      ovary is a follicular regulator capable of stimulating inhibin secretion. DS and
      inhibin were determined by RIA in residual serum samples from in vitro
      fertilization cycles and analyzed along with other parameters using analysis of
      variance and stepwise multiple linear regression after log transformation of the
      RIA data. It was predicted that the serum concentration of inhibin would be
      higher in women with anovulation than in normal subjects and that the serum
      inhibin concentration would have a positive regression coefficient on the serum
      DS concentration. The serum concentrations of inhibin (P < 0.01) and estradiol (P
      < 0.001) on the day of hCG treatment were higher in women with anovulation than
      in normal subjects, as was the number of oocytes retrieved (P < 0.001). The FSH
      and LH doses (both P < 0.005) and age (P < 0.001) were significantly lower, and
      the average duration of gonadotropin therapy was 1 day shorter (P < 0.001) in
      anovulatory patients. There was no significant difference in serum DS (P > 0.2).
      Regression analysis showed that serum inhibin was positively related to the
      number of oocytes (P < 0.001) and serum DS (P = 0.05), with an increase in
      anovulatory subjects (P < 0.025). The duration of treatment with gonadotropins
      was related positively to the patient's age (P < 0.001) and negatively to serum
      DS (P < 0.025), with a decrease in anovulatory subjects (P < 0.025). The number
      of oocytes obtained was negatively related to age (P < 0.001) and positively to
      serum DS (P < 0.005). These data are consistent with a stimulatory effect of
      follicular T derived from either circulating DS or the anovulatory ovary, which
      affects the secretion of inhibin, the duration of gonadotropin treatment, and the
      number of oocytes retrieved.

PMID- 8288698
TI  - Lipolysis during abdominal surgery.
AB  - Subcutaneous adipose tissue lipolysis has been monitored with microdialysis
      during elective cholecystectomy by laparotomy in otherwise healthy nonobese
      subjects. Eight of the subjects received saline and seven received glucose iv
      during the operation. In both groups the glycerol level in the microdialysate
      (lipolysis index) started to increase steadily from the start of the general
      anesthesia until the abdominal wall was closed. Thereafter it leveled off and
      remained elevated until after extubation. Plasma glycerol started to rise after
      the surgical incision. The levels of noradrenaline and adrenaline, but not of
      insulin, glucagon, and cortisol in plasma, changed in parallel with that of
      glycerol in the microdialysate. The glycerol response in adipose tissue in the
      group receiving iv glucose was three times more marked than in the saline group
      (P = 0.01) in spite of marked hyperinsulinemia, but there was no difference
      between the groups in plasma glycerol response. The plasma noradrenaline response
      was 50% higher (P = 0.03) in the glucose group than in the saline group, but
      there was no difference between the groups in the plasma adrenaline, glucagon, or
      cortisol responses. Adipose tissue blood flow was measured by the escape of
      ethanol from the dialysis solvent into the extracellular space. It was constant
      throughout the experimental period in both groups. In conclusion, the lipolysis
      rate is accelerated during general anesthesia and abdominal surgery because of
      increased catecholamine production. Perioperative glucose infusion is associated
      with a further acceleration of the lipolytic rate in subcutaneous adipose tissue
      due to an additional activation of the sympathetic nervous activity that
      overrides the antilipolytic effect of the glucose-induced hyperinsulinemia. Other
      adipose regions may be less sensitive to glucose infusions and anesthesia.

PMID- 8288699
TI  - Androgens induce prolactin production by human endometrial stromal cells in
      vitro.
AB  - Although there is a significant quantity of androgens in the endometrium, the
      function of these hormones has not been clarified, except for being estrogen
      precursors. Human endometrial stromal cells (ESC) were cultured in the presence
      of testosterone (T) and 5 alpha-dihydrotestosterone. Following culture, prolactin
      (PRL), a biochemical marker of stromal cell differentiation (decidualization)
      which is produced by ESC, was examined. T induced PRL production in a time- and
      dose-dependent manner, as reported previously for progesterone (P) stimulation.
      In addition, 5 alpha-dihydrotestosterone, which cannot be converted to estrogens,
      similarly induced PRL production. T in combination with P enhanced PRL production
      in cultured ESC significantly more than either P or T stimulation alone. A
      specific androgen receptor blocker, flutamide, when added to cultures containing
      T, inhibited PRL production in a dose-dependent manner, but did not affect the
      production of PRL induced by P. These results indicate that in vitro PRL
      production by human ESC is induced not only by P, but also by androgens through
      specific receptors and further suggest that androgens play an important role in
      human endometrial differentiation.

PMID- 8288700
TI  - Glucose counterregulatory response to acute hypoglycemia in hyperthyroid human
      subjects.
AB  - To evaluate the impact of hyperthyroidism on the counterregulatory response to
      hypoglycemia, eight hyperthyroid and eight sex-, age-, and body mass index
      matched healthy women were given an iv insulin bolus (0.1 U/kg BW), and blood was
      drawn from 0-120 min for glucose, epinephrine, norepinephrine, glucagon, GH,
      ACTH, and cortisol measurements. In the basal state plasma glucose, GH, and
      cortisol levels were similar in the two groups, whereas plasma glucagon and ACTH
      were increased (135 +/- 17 vs. 80 +/- 10 ng/L and 6.4 +/- 1.5 vs. 2.6 +/- 0.4
      pmol/L, respectively; both P < 0.025), and plasma catecholamines were reduced
      [epinephrine, 142 +/- 25 vs. 371 +/- 71 pmol/L (P < 0.025); norepinephrine, 0.41
      +/- 0.07 vs. 1.41 +/- 0.12 nmol/L (P < 0.001)] in hyperthyroid patients. After
      insulin injection, plasma glucose similarly declined in the two groups (nadir,
      1.5 +/- 0.2 vs. 1.6 +/- 0.2 mmol/L). Conversely, recovery from hypoglycemia was
      significantly faster in the hyperthyroid patients. In this respect, it is
      noteworthy that the plasma glucagon response had remarkably increased in the
      latter (peak, 444 +/- 56 vs. 198 +/- 17 ng/L; P < 0.005). On the other hand, the
      epinephrine responses were similar in the two groups, whereas norepinephrine
      levels remained consistently lower (peak, 0.97 +/- 0.20 vs. 2.61 +/- 0.24 nmol/L;
      P < 0.001), and the GH increase was severely impaired (peak, 10.6 +/- 1.9 vs.
      29.6 +/- 6.2 micrograms/L; P < 0.01) in hyperthyroid patients. Plasma ACTH
      remained slightly higher in hyperthyroid subjects, but there were no substantial
      differences in the cortisol response between the two groups. In conclusion,
      hyperthyroidism affects plasma levels of several counterregulatory hormones,
      either in the fasting state or after insulin-induced hypoglycemia, with increased
      efficiency of plasma glucose recovery from hypoglycemia.

PMID- 8288701
TI  - In vitro production of plasminogen activator by human granulosa cells.
AB  - Plasminogen activator (PA) production by granulosa cells has been demonstrated in
      several species. In the human ovary, tissue-type PA and urokinase-type PA
      antigens have been found in the follicular fluids, but neither PA activity nor
      mRNA for both enzymes was found in granulosa cells of preovulatory follicles. All
      of these studies were performed on granulosa cells collected from follicles
      immediately before ovulation, when the cells were already in the luteal phase. In
      the attempt to better characterize the PA/plasminogen system in the human ovary,
      we examined PA and PA inhibitor (PAI) production in cultures of granulosa cells
      obtained from normally cycling untreated women at different stages of the cycle.
      In addition, we analyzed granulosa-luteal cells obtained from hormonally
      stimulated women undergoing gamete intrafallopian tube transfer, as a model of
      late phase follicular development. Zymographic analysis as well as
      immunoprecipitation with specific antisera revealed that granulosa cells from
      follicles at early phases of antral stages secreted high levels of PA of the
      urokinase type in the medium. No free tissue-type PA activity was found in any of
      the examined samples. On the contrary, free PAI was undetectable in medium
      obtained from granulosa cell cultures, and it was abundant in granulosa-luteal
      cell cultures, where it was found in two forms. These data show that in the human
      ovary as in that of the rat, PAs and PAIs are tightly time regulated. The timing
      of PA production in human granulosa cells suggests a role for PA activity at
      early stages of follicular maturation.

PMID- 8288702
TI  - Production of bioactive and immunoreactive interleukin-6 (IL-6) and expression of
      IL-6 messenger ribonucleic acid by human pituitary adenomas.
AB  - Preliminary studies have demonstrated that some pituitary adenomas secrete
      immunoreactive interleukin-6 (irIL-6) when cultured in vitro. We have extended
      these studies by investigating 100 pituitary adenomas of different types
      measuring immunoreactive and bioactive IL-6. Tumors were cultured either as
      explants without fetal calf serum or as dispersed cells with 10% total calf
      serum. Fifty-three of the 100 (53%) pituitary cultures were found to release irIL
      6 and in 44 adenomas examined, 32 (72.7%) secreted bioactive IL-6. In 61 explant
      cultures, 30 adenomas released IL-6, indicating autonomous secretion. The amount
      of IL-6 released by adenomas in cell culture was generally higher, although the
      incidence was similar to explant cultures. IrIL-6 was released by 7 of 14
      prolactinomas, 15 of 27 somatotrophinomas, 5 of 7 corticotrophinomas (including 2
      Nelson's adenomas), 1 of 1 thyrotrophinomas, 2 of 2 gonadotrophinomas, and 23 of
      49 clinically non-functioning adenomas. Periadenomatous tissue removed from a
      patient with a corticotrophinoma was found to secrete IL-6 but in much lower
      concentration than from the adenoma tissue. Tumor necrosis factor-alpha and 
      gamma-interferon were not detected in the conditioned media. Four IL-6-secreting
      adenomas were examined by in situ hybridization for IL-6 messenger RNA, and three
      of these were positive with fluorescence present throughout the tissue examined.
      We have provided evidence that over half of pituitary adenomas secrete IL-6 which
      is bioactive and that IL-6 is synthesized within the tumor by the adenoma cells.

PMID- 8288703
TI  - Diagnostic use of recombinant human thyrotropin in patients with thyroid
      carcinoma (phase I/II study).
AB  - Current diagnostic studies [radioiodine uptake and serum thyroglobulin (Tg)
      levels] for residual or metastatic thyroid tissue in patients with differentiated
      thyroid carcinoma require a hypothyroid status necessary for adequate endogenous
      TSH stimulation. However, almost all patients have symptoms of clinical
      hypothyroidism during this period. As shown in the present study, recombinant
      human TSH (rhTSH) allows stimulation of 131I uptake and Tg release from residual
      thyroid tissue in euthyroid patients. To assess safety, dosage, and preliminary
      efficacy, comparison was made of the stimulation of 131I uptake and Tg release
      after rhTSH administration and after T3 withdrawal in 19 patients after a recent
      thyroidectomy for differentiated thyroid carcinoma. Various doses (10-40 U) of
      rhTSH were injected im for 1-3 days in patients receiving suppressive doses of
      T3. Twenty-four hours after the last dose of rhTSH, 1-2 mCi 131I were
      administered, followed by a neck and whole body scan 48 h later. After
      discontinuing T3 for a median period of 19 days (range, 15-28), endogenous serum
      TSH levels were markedly elevated, and the patients were given a second dose of
      131I and rescanned 48 h later. The injections of rhTSH were tolerated well. No
      major adverse effects were reported; nausea was reported in 3 (16%) and vomiting
      in 1 of the patients treated with high doses. The quality of life, as measured by
      two psychometric scales, was far better during rhTSH treatment than after T3
      withdrawal. The peak levels of serum TSH (mean +/- SD) after a single dose of 10,
      20, or 30 U were 127 +/- 19, 309 +/- 156, and 510 +/- 156 mU/L, respectively, and
      occurred 2-8 h after injection. Twenty-four hours after the injection, TSH levels
      decreased to 83 +/- 31, 173 +/- 73, and 463 +/- 148 mU/L in these treatment
      groups, respectively. The quality of the thyroid scans and the number of sites of
      abnormal 131I uptake were similar after rhTSH treatment and in the hypothyroid
      scans in 12 (63%) patients. Two additional sites of uptake in the chest and one
      in the thyroid bed, not visible on the hypothyroid scans, were identified in 3
      (16%) patients after rhTSH. In 1 patient a focus of uptake was better visualized
      after rhTSH than after withdrawal. In 3 (16%) other patients, 1 lesion in the
      chest and 2 in the neck were seen only after T3 withdrawal.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8288704
TI  - Pharmacokinetics of 17 beta-dihydroequilin sulfate and 17 beta-dihydroequilin in
      normal postmenopausal women.
AB  - The MCRs of 17 beta-dihydroequilin sulfate and 17 beta-dihydroequilin were
      determined in normal postmenopausal women by single iv injection of either 17
      beta-[3H]dihydroequilin sulfate ([3H]17 beta-EqS) or 17 beta-[3H]dihydroequilin
      ([3H]17 beta-Eq). After the administration of [3H]17 beta-EqS, blood was drawn at
      various time intervals, and the plasma obtained was fractionated into the
      unconjugated, sulfate, and glucuronide fractions. The bulk of radioactivity was
      present in the sulfate fraction, and from this [3H]17 beta-EqS, [3H]equilin
      sulfate, [3H]equilenin sulfate, and 17 beta-[3H]dihydroequilenin sulfate were
      isolated and purified, and their concentrations were measured. The disappearance
      of [3H]17 beta-EqS from plasma can be described as a function of two
      exponentials. The half-life of the initial fast component was 5 +/- 0.2 min; this
      component represents the distribution and transfer from a space, with a mean
      volume (V1) of 6 +/- 0.5 L. The value for the rate constant (k) of total removal
      from this space was 300 +/- 20 U/day, of which 35 +/- 2% was irreversible. The
      mean half-life of the slower component of 17 beta-EqS was 147 +/- 15 min, and the
      mean MCR was 376 +/- 93 L/day.m2. Similarly, after the administration of [3H]17
      beta-Eq, the disappearance of radioactivity as 17 beta-Eq from plasma also had
      two components. The half-lives of the fast and slow component were 5.5 +/- 0.8
      and 45 +/- 2.0 min, respectively. The MCR of 17 beta-Eq was 1252 +/- 103
      L/day.m2. From both series of experiments, unconjugated and sulfate-conjugated
      equilin, equilenin, and 17 beta-dihydroequilenin were isolated and purified, and
      their concentrations were measured. No 17 alpha-reduced metabolites were
      detected. These results indicate that 17 beta-EqS is cleared twice as fast as
      equilin sulfate (MCR, 176 L/day.m2), whereas the more potent estrogen 17 beta-Eq
      is cleared 2 times slower than equilin. The slower elimination and greater
      estrogenic activity of 17 beta-Eq support the hypothesis that the major in vivo
      activity of equilin sulfate present in conjugated equine estrogen preparations is
      expressed via its metabolites 17 beta-EqS and 17 beta-Eq.

PMID- 8288705
TI  - Local production and action of follistatin in human placenta.
AB  - The aim of the present study was to investigate the possible production,
      localization, and action of follistatin in human placenta, fetal membranes
      (amnion, chorion), and maternal decidua. Four different experimental approaches
      were used: 1) Southern blot analysis following reverse polymerase chain reaction
      to identify follistatin messenger RNA (mRNA) in tissue homogenates; 2)
      immunohistochemistry to localize immunoreactive (ir-) follistatin in the various
      intrauterine tissues; 3) measurement by RIA of ir-follistatin levels in culture
      medium of placental cells; and 4) possible action of follistatin on human CG
      (hCG) and progesterone release from cultured placental cells. Placental and
      decidual cells collected during first trimester or at term gestation express
      follistatin mRNA; fetal membranes (amnion, chorion) at term also express
      follistatin mRNA. Immunoreactive follistatin is localized in syncytial cells of
      placental villi at term as well as in large decidual cells, in amnion epithelium,
      and in chorionic cells. The placental secretion of follistatin has been confirmed
      by the evidence of measurable levels of ir-follistatin in the medium of cultured
      placental cells at term; the release is time dependent and is not modified by the
      addition of forskolin or progesterone. The addition of increasing doses of
      recombinant human follistatin does not significantly influence the release of hCG
      or progesterone from cultured placental cells, whereas the activin A-induced hCG
      and progesterone release are completely reversed. The present data showed that 1)
      human placenta, fetal membranes, and decidua express follistatin mRNA; 2) ir
      follistatin is localized and released from placental cells at term; and 3)
      follistatin has a functional role in the local control system regulating
      placental hormone production.

PMID- 8288706
TI  - Effects of hydrocortisone on pulsatile pituitary glycoprotein secretion.
AB  - During states of stress, hypothalamic-pituitary-thyroid and hypothalamic
      pituitary-gonadal function can be suppressed. One putative mediator of this
      stress response may be glucocorticoids, which have widespread effects on thyroid
      and gonadal function. To characterize dynamic pituitary glycoprotein secretion
      during glucocorticoid administration, 24-h TSH, LH, FSH, and alpha-subunit pulses
      were measured in 10 healthy young subjects on 3 occasions: 1) at baseline, 2)
      during infusions of 100 mg hydrocortisone (HC) over 24 h, and 3) during infusions
      of 300 mg HC over 24 h. These HC infusions led to serum cortisol levels similar
      to the endogenous cortisol levels seen in moderate and severe stress. Both HC
      infusions had profound rapid effects on TSH levels, decreasing TSH pulse
      amplitude by 60% and abolishing the nocturnal TSH surge. However, TSH pulse
      frequency was unaltered. In contrast, HC infusions did not change mean or
      pulsatile LH, FSH, or alpha-subunit secretion. These results suggest that stress
      levels of cortisol acutely suppress TSH secretion at the pituitary level, with
      little effect on the TSH pulse generator. On the other hand, the effects of
      stress and/or hypercortisolism on the gonadal axis may require higher cortisol
      levels, more prolonged exposure, or other mediators of the stress response.

PMID- 8288707
TI  - Immunohistochemical localization of estradiol and progesterone receptors in human
      uterus throughout pregnancy: expression in endometrial blood vessels.
AB  - Although progesterone and estrogens are essential to maintain human pregnancy
      after implantation, the localization of their specific receptors in different
      uterine cell types during pregnancy has not been investigated. We studied uteri
      (n = 40) obtained during the first 3 months of pregnancy (n = 21) and in late
      pregnancy (n = 9) as well as from women 5-14 weeks pregnant (n = 10) who had
      received the antiprogestagen RU 38486 (Roussel-UCLAF) to induce cervical
      dilation. Frozen tissues were processed for indirect immunocytochemical staining
      with specific monoclonal antibodies against estrogen receptors (ER; Abbott
      Laboratories) and progesterone receptors (PR; Li 417). Specific staining for
      steroid receptors was only detected in the nucleus. In the endometrium, PR
      staining remained fairly constant throughout pregnancy, whereas ER staining was
      initially weak and then undetectable. PR was widely expressed in stromal cells
      and in spiral arterial wall cells, whereas ER was expressed in scattered stromal
      cells and arterial cells. Both PR and ER were absent from glandular epithelium,
      contrasting with the secretory activity during the first trimester. Spiral
      arteries of the endometrium and myometrial smooth muscle cells showed intense PR
      and moderate ER staining in early pregnancy. The progesterone antagonist RU 38486
      (mifepristone), given in early pregnancy at a dose of 200 mg, caused a marked
      increase in ER staining and a smaller increase in PR staining in stromal cells,
      whereas the glandular epithelium remained negative for both ER and PR (except for
      one and two specimens, respectively). We conclude the following. 1) Stromal cells
      retain PR despite the high progesterone levels during pregnancy, in keeping with
      the role of progesterone in stromal decidualization. The absence of PR from the
      secretory glandular epithelium suggests a paracrine link between decidualized
      stromal cells and epithelial cells. 2) Significant PR down-regulation by
      progesterone during pregnancy occurs only in epithelial cells of the endometrium.
      3) In contrast, the absence or low level of ER staining in the various cell types
      of the endometrium during gestation concurs with the known effect (down
      regulation) of steroid hormones on ER mRNA or protein levels. The increase in ER
      in human decidua after RU 38486 treatment indicates that the main cause of the
      low ER levels is progesterone secretion. 4) The intense PR staining in smooth
      muscle cells of spiral arteries during early pregnancy suggests that progesterone
      is essential for modulating blood flow during pregnancy.

PMID- 8288708
TI  - Immunohistochemical localization of dehydroepiandrosterone sulfotransferase in
      human fetal tissues.
AB  - Sulfurylation of many steroid hormones has been found to occur in several tissues
      of the fetal and adult human. Because the production of prodigious quantities of
      dehydroepiandrosterone sulfate in the developing fetus is believed to be of
      signal importance in the hyperestrogenic state that is characteristic of human
      pregnancy, we sought to define the tissue sites that contain
      dehydroepiandrosterone sulfotransferase (DST). To this end, antibodies directed
      against purified human liver DST were employed for the immunohistochemical
      localization of DST in several fetal tissues. Abundant DST was found in the fetal
      and neocortical zones of the adrenal cortex, liver, testis, and intestine.
      Collecting ducts of the kidney were weakly positive for DST. DST immunostaining
      was not observed in spleen, thymus, lung, brain, heart, stomach, pancreas, or
      skeletal muscle. The tissue localization of DST immunoreactivity is consistent
      with the reported localization of enzymatic activity determined during in vitro
      studies on sulfurylation of C19 and C21 steroids. On the other hand, DST
      localization does not correspond as well to the sites of estrogen sulfurylation
      found by others. These data suggest that a single enzyme may be responsible for
      sulfurylation of C19 and C21 steroids in the developing human.

PMID- 8288709
TI  - Hyperuricemia and insulin resistance.
AB  - The associates of gout-obesity, hypertriglyceridemia, glucose intolerance, and
      hypertension, strikingly resemble those of insulin resistance. In the present
      study we determined whether hyperuricemia is associated with insulin resistance
      and, if so, whether this association can be explained by other components of the
      syndrome. For this purpose we quantitated insulin sensitivity (euglycemic clamp)
      in 37 nondiabetic subjects (aged 30-68 yr) exhibiting varying degrees of the
      metabolic syndrome (body mass index, 21.5-35.7 kg/m2; serum triglycerides, 0.4
      22.0 mmol/L; high density lipoprotein cholesterol 0.38-1.86 mmol/L; blood
      pressure, 190-100/116-60 mm Hg). In simple linear regression analysis, the serum
      uric acid concentration (range, 182-568 mumol/L) was inversely correlated with
      insulin sensitivity (rate of glucose utilization; r = -0.61; P < 0.001) and
      positively with serum triglycerides (r = 0.68; P < 0.001), but not with body mass
      index, age, or the plasma glucose concentration. In multiple linear regression
      analysis, both insulin sensitivity (P < 0.05) and serum triglycerides (P < 0.005)
      were independently associated with the serum uric acid concentration, and
      together explained 50% of its variation. Addition of body mass index or age to
      the model did not improve the degree of explanation. Acute elevation of serum
      triglycerides about 3-fold, of plasma FFA about 9-fold, or of serum insulin about
      28-fold had no effect on the serum uric acid concentration in healthy volunteers.
      The data indicate that hyperuricemia is indeed an inherent component of the
      metabolic syndrome and could also be used as a simple marker of insulin
      resistance.

PMID- 8288711
TI  - Implementing ethical guidelines for publication of research in Endocrine Society
      Journals.

PMID- 8288710
TI  - Mechanism of abnormal production of adrenal androgens in patients with
      adrenocortical adenomas and carcinomas.
AB  - The production of adrenal androgens can be modulated by the activities of
      steroidogenic enzymes and by the electron transfer system, NADPH-cytochrome P450
      reductase (Red) and cytochrome b5 (b5), both of which have been shown to increase
      17,20-lyase activity in vitro. To clarify the mechanism of diminished secretion
      of adrenal androgens in patients with adrenocortical adenoma and Cushing's
      syndrome and of excess secretion in patients with adrenocortical carcinoma, we
      investigated the enzymatic activities of cytochrome P45017 alpha, 3 beta
      hydroxysteroid dehydrogenase (3 beta-HSD), and Red as well as the content of b5
      in five adenomas, three carcinomas, and two normal adrenal glands. An in vitro
      enzyme assay using a microsomal fraction of the tissues indicated that all the
      tumors had almost the same degree of 17 alpha-hydroxylase activities as the
      normal adrenals. However, the relative activity ratio of 17,20-lyase to 17 alpha
      hydroxylase of the three adenomas was markedly diminished, and 3 beta-HSD
      activity was apparently lower in the three carcinomas. The messenger RNA
      concentrations of P45017 alpha were similar in all tumors, whereas those of 3
      beta-HSD were markedly lower in the carcinomas than in other tissues. Both the
      content of b5 and the activity of Red were significantly lower in the adenomas.
      These results suggest that low concentrations of adrenal androgens in patients
      with adrenocortical adenomas are mainly due to low 17,20-lyase activity, which
      may be explained in part by a lower content of b5 and Red. In addition, high
      concentrations of adrenal androgens in patients with adrenocortical carcinoma are
      mainly due to the diminished activity of 3 beta-HSD.

PMID- 8288712
TI  - Pulse amplitude and frequency modulation of parathyroid hormone in early
      postmenopausal women before and on hormone replacement therapy.
AB  - Although the pathophysiology of postmenopausal osteoporosis has been investigated
      extensively, it is still not established in what respect PTH is related to the
      events. Recently, consistent data on the pulsatile secretion of PTH in man have
      been published. In this study intact PTH was measured in six early postmenopausal
      women before and after 6 months of hormone replacement therapy (HRT; 0.6 mg
      conjugated estrogens and 5 mg medrogestone). In addition to parameters of calcium
      metabolism and bone mass and to control HRT, intact PTH was measured in blood
      drawn over 6 h every 2 min. With HRT there was a 30% reduction in PTH secretion.
      Both the amount secreted per pulse (baseline, 26.8 +/- 6.9 ng/L; HRT, 21.4 +/-
      7.6 ng/L; P < 0.05) as well as the basal secretion (baseline, 232.6 +/- 117.6
      ng/L.h; HRT, 145.5 +/- 80.0 ng/L.h; P < 0.01) were reduced, whereas the pulse
      count per h remained constant (baseline, 5.1 +/- 2.2; HRT, 5.1 +/- 1.3). Power
      spectrum analysis showed a shift in spectral maxima consistent with these
      findings. Ionized and total calcium were slightly, but nonsignificantly, reduced
      with treatment. In summary we conclude that in early postmenopausal women, HRT
      reduces the secretion of PTH by reducing both the basal secretion and the amount
      secreted per pulse. It is conceivable that some of the known effects of HRT on
      bone metabolism might be mediated by the modulation of PTH secretion.

PMID- 8288713
TI  - Pulse amplitude and frequency modulation of parathyroid hormone in primary
      hyperparathyroidism.
AB  - Pulsatile secretion of PTH in human subjects has been described recently.
      However, the pattern of PTH secretion in primary hyperparathyroidism (pHPT)
      remains to be characterized. In this study intact PTH was measured in 9 female
      patients with pHPT. As a control group we present data from 10 postmenopausal
      women. In addition to parameters of calcium metabolism and bone mass, PTH was
      measured in samples drawn over 4 or 6 h every 2 min by central venous blood
      sampling. The mean intact PTH concentration was 39.0 +/- 20.3 ng/L in healthy
      women and 193.2 +/- 127.9 ng/L in female patients with pHPT (P < 0.01). Pulse
      rhythm analysis showed significant differences between both groups for total PTH
      secretion per h (patients, 1196.4 +/- 485.3 ng/L; control group, 271.7 +/- 132.2
      ng/L), basal PTH secretion per h (patients, 852.4 +/- 459.1 ng/L; control group,
      185.6 +/- 126.1 ng/L), and average PTH secretion per pulse (patients, 112.6 +/-
      54.8 ng/L; control group, 23.2 +/- 7.1 ng/L). Both patients and control subjects
      had, on an average, five pulses per h, and the pulsatile secretion accounted for
      about 50% of the total secretion. Differences in power spectrum analysis were
      consistent with these findings. The cross-correlation of PTH and calcium
      indicates an impaired feedback regulation in pHPT. PTH secretion in female
      patients with pHPT results from both an increased basal secretion and an
      increased amplitude of PTH pulses. Other features of secretion are the same as
      those in normal women. Feedback regulation of PTH and calcium is impaired in
      pHPT.

PMID- 8288714
TI  - Postpartum thyroiditis and familial dysalbuminemic hyperthyroxinemia.
AB  - Familial dysalbuminemic hyperthyroxinemia (FDH) is a syndrome associated with
      euthyroidism and increased binding of T4 to serum albumin. The combined
      occurrence of FDH and postpartum hyperthyroidism due to Graves' disease has only
      been reported in one patient. We now describe the first case of FDH and
      thyrotoxicosis due to postpartum silent thyroiditis. In a 19-yr-old woman, FDH,
      suspected on the basis of strikingly elevated analog free T4 (fT4) and total T4
      values, but normal two-step fT4 and serum TSH values, was confirmed by [125I]T4
      agarose-gel electrophoresis. When FDH and thyrotoxicosis, characterized by
      markedly elevated analog fT4, total T4, and two-step fT4 values and undetectable
      TSH values, coexist, the differential diagnosis may be confusing.

PMID- 8288715
TI  - Clinical review 53: The endocrinology of vasoactive peptides: synthesis to
      function.

PMID- 8288716
TI  - The effects of corticotropin and growth hormone releasing hormones on their
      respective secretory axes in chronic hemodialysis patients before and after
      correction of anemia with recombinant human erythropoietin.
AB  - Endocrine abnormalities in chronic hemodialysis patients are in part corrected by
      control of anemia with recombinant human erythropoietin (rHu-EPO). We further
      examined the role of rHu-EPO in select hormonal abnormalities thought to be
      anemia related as well as the GH-insulin-like growth factor 1 (GH-IGF-1) axis
      that is abnormal in hemodialysis patients. We studied responses to the
      administration of two hypothalamic hormones, GHRH and ovine corticotropin
      releasing hormone (CRH), in five anemic male patients on chronic hemodialysis
      before and after correction of the anemia with rHu-EPO. For comparison, five age
      matched normal male volunteers were tested once. Anemic patients on chronic
      hemodialysis had high basal GH concentrations, an exaggerated GH response to
      exogenous GHRH, increased levels of IGF-1, and elevated levels of IGF-1 binding
      protein-3 in comparison to controls. ACTH response to CRH was comparable in
      dialysis patients and normal controls, but the cortisol response to endogenous
      ACTH release was prolonged. The cortisol binding globulin was similar to the
      controls. After correction of anemia, the basal elevation of GH was no longer
      present, but the exaggerated response of GH to exogenous GHRH persisted. IGF-1
      and IGF-1 binding protein-3 levels remained elevated. The ACTH response to CRH,
      which was normal before correction of the anemia, became exaggerated in terms of
      elevated levels. Nevertheless, the prolonged cortisol response persisted. It
      appears that correction of the anemia in hemodialysis patients with rHu-EPO can
      partly correct perturbations in the GH secretory axis but may lead to new
      abnormalities in the CRH-ACTH axis.

PMID- 8288717
TI  - Maternal plasma progesterone levels fall after rectal administration of estriol.
AB  - Maternal plasma unconjugated estriol (E3), progesterone (P), and estradiol (E2)
      levels were measured at 30-min intervals for 6 h after the rectal administration
      of a 100-mg E3 or placebo suppository to 28 pregnant women at term. Mean plasma
      unconjugated E3 levels showed a sustained rise approximately 50% above baseline
      levels 2 h after rectal E3 administration (P < 0.003). There was a simultaneous
      sustained fall of approximately 20% in mean plasma P levels (P < 0.05); the fall
      in mean P levels was greatest in the women who delivered within 48 h of E3
      suppository administration (P < 0.05). There was no change in mean plasma E2
      levels. This study demonstrates that a significant rapid increase in maternal
      circulating E3 levels can be obtained by the rectal administration of E3, and
      that this increase in maternal E3 levels is associated with a decrease in
      circulating P levels.

PMID- 8288718
TI  - Association of human corticotropin-releasing hormone to its binding protein in
      blood may trigger clearance of the complex.
AB  - Late in the last trimester of human pregnancy, as plasma CRH levels rise, the
      concentration of circulating CRH-binding protein (CRH-BP) falls. We have
      investigated, using nonpregnant subjects, the hypothesis that CRH has a negative
      effect on plasma levels of CRH-BP. A specific RIA developed with the aid of
      recombinant binding protein has been used to measure CRH-BP. Subjects given iv
      infusions of human CRH for 10 h showed a sustained fall in plasma CRH-BP for the
      duration of the infusion. Intravenous bolus injection of human CRH produced a
      rapid reduction in CRH-BP levels to 54% of the basal value, whereas ovine CRH was
      without effect, even though both peptides are cleared from the plasma at similar
      rates and have similar effects on the pituitary-adrenal axis. The rapid clearance
      was concluded to be related to ligand affinity, as ovine CRH has a 200-fold lower
      affinity than human CRH for CRH-BP. We suggest that the rising levels of CRH are
      responsible for the reduction in CRH-BP concentrations observed in late
      pregnancy, and that this reduction is triggered by the binding of CRH-BP to its
      ligand.

PMID- 8288719
TI  - Preoperative localization of parathyroid tissue with technetium-99m sestamibi
      123I subtraction scanning.
AB  - To evaluate the utility of technetium-99m (Tc-99m) sestamibi for visualization of
      functioning parathyroid tissue, 14 subjects underwent Tc-99m sestamibi 123I
      subtraction scanning as part of the preoperative evaluation for
      hyperparathyroidism. Informative scans were obtained in 13 subjects, including 7
      patients with recurrent or persistent hyperparathyroidism, and correctly
      identified the location of the hyperfunctioning parathyroid tissue found at
      surgery. In all informative patients, hyperparathyroidism was due to adenomatous
      disease or hyperplasia secondary to renal failure. Successful scans were obtained
      with glands as small as 220 mg. In the lone patient in whom Tc-99m sestamibi
      scanning failed to localize hyperfunctioning parathyroid tissue, surgery revealed
      a 1700-mg hyperplastic parathyroid neoplasm in the neck. In no case did a Tc-99m
      sestamibi scan suggest parathyroid tissue where there was none. In 1 case, a
      patient presented with persistent hyperparathyroidism after 1 neck and a second
      combined neck and mediastinal exploration. Tc-99m sestamibi imaging revealed
      uptake in the periaortic region, and a 570-mg adenoma was found in the
      aortopulmonary window. Using only initial studies, prospective evaluation
      provided a sensitivity of 78.5% and a positive predictive value of 100%. After
      repeat studies in 5 patients, 2 of 3 patients with initially negative results and
      technically deficient scans became positive on restudy. Inclusion of these
      studies increased sensitivity to 93%. Tc-99m sestamibi 123I subtraction scanning
      appears to be a reliable noninvasive method for preoperative localization of
      hyperfunctioning parathyroid tissue.

PMID- 8288720
TI  - In situ hybridization study of estrogen receptor messenger ribonucleic acid in
      human adenohypophysial cells and pituitary adenomas.
AB  - Estrogen receptor (ER) was demonstrated in nontumorous and adenomatous human
      pituitaries by autoradiography and biochemical assays. In the present study, we
      investigated ER mRNA by in situ hybridization applied on paraffin section of 9
      nontumorous pituitaries obtained at surgery or autopsy and 109 surgically removed
      adenomas. In nontumorous pituitaries, in situ hybridization combined with
      immunocytochemistry revealed hybridization signal in GH-, PRL-, ACTH-, TSH-, and
      LH/FSH-immunoreactive cells, with the highest intensity in PRL-immunoreactive
      cells. ER mRNA was also localized in Crooke's cells, corticotrophs extending to
      posterior lobe, cells lining the pars intermedia cavities, and squamous nests of
      pars tuberalis. The neurohypophysis, endothelium, and connective tissue expressed
      no ER gene. ER mRNA was present in all adenoma types, including somatotroph,
      lactotroph, mixed somatotroph-lactotroph, mammosomatotroph, acidophil stem cell,
      functioning and silent corticotroph, thyrotroph, gonadotroph, null cell adenomas,
      and oncocytomas. The strongest signal was seen in some lactotroph and
      mammosomatotroph adenomas. In 9 lactotroph adenomas exposed to bromocriptine
      (long-acting repeatable injectable form), the hybridization signal was weak or
      absent, suggesting that suppression of ER gene plays a role in the inhibition of
      PRL synthesis and tumor growth.

PMID- 8288721
TI  - ras mutations in human prolactinomas and pituitary carcinomas.
AB  - Pituitary adenomas have been shown to be clonal in origin, indicating that one or
      more somatic mutations underlie tumor pathogenesis. Mutated oncogenic forms of
      ras protein have been identified in a number of human neoplasms, including
      thyroid adenomas and carcinomas. However, the potential role of activated ras in
      the development of specific human pituitary tumor phenotypes has not been
      determined. Although ras mutations were not found in glycoprotein hormone
      secreting or somatotroph adenomas, we recently identified a mutation in the H-ras
      gene (Gly-Val) at codon 12 in a highly invasive prolactinoma. These data raise
      the possibility that ras mutations might play a role in the pathogenesis of PRL
      secreting pituitary tumors and/or may be a marker for tumor invasiveness and
      malignant transformation. Therefore, we investigated 78 pituitary tumors (59
      prolactinomas, 13 invasive prolactinomas, and 6 pituitary carcinomas) for
      activating point mutation in the three ras genes using oligonucleotide-specific
      hybridization. In contrast to the relatively high frequency of ras mutations in
      many different tumor types, no ras mutations were identified in either
      prolactinomas or pituitary carcinomas. Our data indicate that ras mutations are
      rare in prolactinomas and pituitary carcinomas.

PMID- 8288722
TI  - Resistance to autoimmune thyroid disease is associated with HLA-DQ.
AB  - Genotypes of DQA1 and DQB1 genes were determined by polymerase chain reaction
      followed by dot blot hybridization with sequence-specific oligonucleotide probes
      in 105 patients with goitrous autoimmune thyroiditis (Hashimoto's thyroiditis)
      and in 67 patients with Graves' disease to investigate whether specific DQ
      alleles were associated with susceptibility or resistance to autoimmune thyroid
      diseases. Hashimoto's thyroiditis was found to be negatively associated with
      DQA1*0102 and DQB1*0602 whereas Graves' disease showed a negative association
      with DQB1*0501. No strongly positive association with a specific DQ allele was
      found in either disease. These results suggest that the HLA-DQ gene may be a
      genetic marker for resistance to autoimmune thyroid diseases.

PMID- 8288723
TI  - Meta-analysis evaluation of the impact of thyrotropin receptor antibodies on long
      term remission after medical therapy of Graves' disease.
AB  - Patients with the hyperthyroidism of Graves' disease (GDH) have a higher risk of
      relapse after antithyroid drug therapy (ATD) therapy when TSH receptor antibodies
      (TRAb) are positive, but the practical clinical implication of TRAb as a
      predictor for relapse is still much debated. This study was undertaken to
      investigate by meta-analysis the results from the literature on the use of TRAb
      as predictor of long term (i.e. at least 1 yr) relapse after ATD. Eighteen
      publications from 1975-1991 fulfilled the criteria of 1) availability of TRAb at
      the end of ATD treatment, 2) at least 1 yr of follow-up after ATD, 3) data
      presentation in a form suitable for meta-analysis, and 4) no other thyroid
      related therapy during the follow-up period. The 10 prospective studies, 5 of
      which measured TSH binding inhibiting immunoglobulins (total n = 597) and 5 of
      which measured thyroid-stimulating antibodies (n = 340), were computed together
      because no significant differences were found. In contrast, retrospective and
      prospective studies differed. In the prospective studies, the odds reduction of
      relapse showed 65% less risk of relapse when TRAb were absent compared to that in
      TRAb-positive patients (P < 0.00001). The present meta-analysis has, thus,
      confirmed in a large number of patients (n = 1524) that absence of TRAb is
      significantly protective against relapse of GDH after ATD treatment. However, 25%
      of the patients are "misclassified," and the main questions arising from the
      study are, therefore, the following. 1) Is it worthwhile to use TRAb as predictor
      of relapse? 2) Should patients with GDH continue ATD until TRAb becomes negative,
      rather than for a fixed period? The available methods for TRAb do not allow
      sufficiently high prediction of relapse or remission after ATD for the individual
      patient.

PMID- 8288725
TI  - Henoch-Schoenlein purpura due to streptokinase.
AB  - The syndrome of Henoch-Schoenlein purpura developed in a 74-year-old woman after
      receiving streptokinase as thrombolytic therapy for an acute myocardial
      infarction. Renal biopsy revealed mesangial hypercellularity with deposits of
      IgA. Skin biopsy also revealed IgA deposition. Immunological studies showed
      evidence of sensitization to streptokinase. Elevated IgG, IgA, IgM, and IgE
      antistreptokinase antibodies were detected in the acute serum. Positive immediate
      skin reactivity to streptokinase was also present. Serum precipitins to
      streptokinase disappeared when IgA was removed from the serum. Positive staining
      with biotinylated streptokinase was seen in the skin in the same pattern of
      distribution as IgA. These findings strongly support the role of streptokinase
      and IgA in the pathogenesis of Henoch-Schoenlein purpura in this patient. A
      control group of streptococcal-infected patients showed no immune response to
      streptokinase. Another control group of streptokinase-treated patients, who had
      no untoward reaction, had elevated immunoglobulin classes and precipitins to
      streptokinase. However, the precipitating antibody was IgG and streptokinase skin
      tests were negative.

PMID- 8288724
TI  - Chronic lymphocytic leukemia cells induce non-T cells to produce IgE in the
      presence of interleukin-4.
AB  - Mononuclear cells from peripheral blood and bone marrow from patients with
      chronic lymphocytic leukemia (CLL) were cultured with interleukin-4 (IL-4) alone
      or with IL-4 and hydrocortisone (HC) in order to induce IgE synthesis. From a
      total of 29 experiments with the cells of 17 different donors an IgE secretion
      was observed only twice. Even in those two cases the IgE was found to be not
      monoclonal. The additional stimulation of CLL cells by polyclonal B cell
      activators induced IgM but not IgE production. When CLL cells were cocultured
      with monocyte-enriched cell preparations (M phi) in the presence of IL-4 and HC,
      a substantial IgE secretion could be obtained, which again consisted of both IgE
      kappa and IgE lambda. Since the irradiation of the M phi but not of the CLL cells
      abolished the formation of IgE, it is likely that the IgE production resided in
      the contaminating B cell population of the M phi. When the M phi were replaced by
      T cell-depleted peripheral blood mononuclear cells (non-T cells), irradiated as
      well as formaldehyde fixed CLL cells were able to stimulate non-T cells to
      secrete IgE in the presence of IL-4 or to potentiate IL-4- and HC-induced IgE
      formation. Furthermore, the coculture of irradiated pure CLL cells and purified B
      cells induced not only IgE but also IgG and IgM production and B cell
      proliferation in the presence of lymphokines. Our findings suggest that CLL
      cells, contrary to current opinion, cannot be induced to produce IgE.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8288726
TI  - Analysis of high and low responses to Staphylococcus aureus and interleukin 2 in
      human B lymphocytes.
AB  - Fixed protein A-bearing staphylococci (SAC) stimulate human B cells via surface
      Ig, whereas IL-2 has been reported to provide a sufficient second signal for
      proliferation and differentiation. Using an ELISPOT assay to count cells
      secreting IgM, IgA, and IgG and flow cytometry with acridine orange to assess
      cell cycle progress, we have found that the purified B lymphocytes of a
      substantial minority (5/13) of healthy volunteers with normal serum Ig levels
      failed to differentiate to Ig secreting cells (ISC) in response to SAC + IL-2
      (IgM, IgA, or IgG secreting cells, < 5% of input B cells). High-responders
      generally formed 10-35% ISC. The proportions of B cells expressing IgG, IgA, IgM,
      or IgD were not different in the two groups. By average linkage cluster analysis,
      SAC/IL-2 high- and low-responders were shown to fall into two separate
      populations with respect to ISC. High- and low-responders tended to remain in the
      same group with repeated testing over several months, although some convergence
      was seen. The low-responders also showed significantly less advancement to late
      G1 and S phase than the high-responders, in the presence of SAC +/- IL-2.
      Induction of IL-2 receptors on B cells by SAC + IL-2 was much greater in high
      responders than in low-responders, as shown by flow cytometry with phycoerythrin
      conjugated IL-2. However, SAC + IL-2 induced transferrin receptors normally in
      low-responders, showing that some early activation steps occur in these cells.
      Low-responder B cells often improved their responses in the presence of
      macrophages and T cell supernatants. Finally, bypassing the surface Ig pathway
      using anti-CD3-activated T cells to stimulate B cells produced normal
      differentiation in low-responder B cells. Thus a subset of clinically normal
      individuals possesses B cells which fail to express IL-2 receptors, proliferate,
      and differentiate normally in vitro in response to SAC + IL-2 yet can respond
      well to alternative activation pathways via T cells, monocytes, and their
      products.

PMID- 8288727
TI  - Effects of lovastatin on natural killer cell function and other immunological
      parameters in man.
AB  - Suppression of cholesterol synthesis by 3-hydroxy-3-methylglutaryl-coenzyme A
      (HMG-CoA) reductase inhibitors, such as lovastatin, has been shown to inhibit
      mitogen stimulated proliferation of natural killer (NK) cells and other
      lymphocytes in vitro. This effect is only partially overcome by provision of
      exogenous free or lipoprotein cholesterol but is reversed by mevalonate,
      suggesting that proliferating lymphocytes have a specific requirement for a
      nonsterol isoprenoid product of mevalonate. The effect of lovastatin (20 mg bid)
      on a range of immune function parameters was determined in a randomized, placebo
      controlled, double-blind ex vivo study in 52 patients with primary
      hypercholesterolemia. No significant differences (P < 0.05) were found between
      lovastatin and placebo groups for basal NK or interleukin-2 (IL-2)-induced cell
      mediated cytotoxicity, PHA-stimulated lymphocyte proliferation, or relative
      numbers of T lymphocytes (CD3+), B lymphocytes (CD19+), total NK cells (CD3-,
      CD16+, CD56+) and CD57+ NK cells or in immunoglobulin levels after 4 or 8 weeks
      of treatment. In contrast to previous in vitro data, no statistically or
      clinically significant changes were observed in any parameter of lymphocyte
      function in patients treated with lovastatin.

PMID- 8288728
TI  - Low lymphocyte interferon-gamma production and variable proliferative response in
      anorexia nervosa patients.
AB  - Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells
      (PBMC) in 14 patients with anorexia nervosa (AN) was significantly lower than in
      14 age-matched healthy controls. Follow-up samples in four patients displayed low
      levels, except in two when they recovered the IFN-gamma production as the
      hormonal cycles were restored. A large interindividual variation for the
      lymphocyte proliferative response was observed in 30 AN patients. DNA synthesis
      of PBMC was normal in 8 patients (27%), significantly increased in 6 (20%) (P <
      0.001), and significantly decreased in 16 (53%) (P < 0.001). IFN-gamma inhibition
      was reversed by culturing a control lymphocyte population with monocytes from
      patients with AN. This was not observed in cultures of control monocytes and AN
      lymphocytes. IL-2 receptor (TAC subunit) was assessed and no difference was found
      in the number of TAC-positive cells between patients and controls. These results
      point out impaired production of the immunomodulator cytokine IFN-gamma as a
      major functional defect of AN peripheral lymphocytes.

PMID- 8288729
TI  - Current status of genetic linkage studies of a major gene that causes CL(P) in
      mice: exclusion map.
AB  - An exclusion map for the major gene that causes nonsyndromic cleft lip with or
      without cleft palate, CL(P), in the A strain family of mice is presented. Because
      of linkage homology between mice and humans, this map should be of value to
      projects intended to map major human gene loci for CL(P). In both species, the
      genetic complexity of the etiology of CL(P) necessitates unusual and candidate
      locus approaches. More than 40% of the mouse genome has been swept. Some
      candidate regions include mouse chromosomes 12, 18, and 19, and candidate loci on
      other chromosomes should include Rara, Tgfa, Bmp2b1, and Igf-2.

PMID- 8288730
TI  - An estimation of the number of susceptibility loci for isolated cleft palate.
AB  - The existence of a major gene (or genes) that contributes significantly to the
      familial clustering of cleft lip with or without cleft palate (CL(P)) has been
      suggested by genetic epidemiology studies and supported by patient-control
      genotype association studies with a candidate gene. Here we present an analysis
      of the familial recurrence risk data for isolated cleft palate (CP) and show that
      an oligogenic model with six genes of equal effect fits the data best. The
      discrimination between alternative models is, however, poor and a major locus
      that explains half of the familial recurrence is plausible. The prospects for
      identification of susceptibility loci for CP are discussed.

PMID- 8288731
TI  - A morphometric analysis of cell densities in facial prominences of the rhesus
      monkey embryo during primary palate formation.
AB  - The mechanisms by which the craniofacial complex undergoes morphogenetic change
      during primary palate formation remain unknown. Although changes in cell
      dispersion and extracellular matrix content are known to be involved in growth of
      embryonic primordia, little information about these parameters is available for
      the mammalian face. The purpose of this study was to analyze cell densities in
      different facial regions of rhesus embryos during primary palate formation. Eight
      serially-sectioned embryos of stages 13 to 18 in the collection at the California
      Primary Research Center, most labeled with 3H-thymidine, were analyzed by making
      regional cell counts at x400 with an ocular micrometer. Three embryos with
      autoradiographic label preserved in every section were used to analyze patterns
      of labeling through the depth of the entire face. The results showed that
      different regions of an embryonic face have significantly different cell
      densities. At the early stages, the cell densities were high in the maxillary
      prominences, and the lateral and medial nasal prominences; whereas cell densities
      were low in midline tissues. At later stages, cell densities were lower in the
      lateral portion of the maxillary prominences than in the nasal prominences.
      Serial counts through the face showed regional variation in individual
      prominences, but central high-density cores did not appear to be present.
      Labeling with 3H-thymidine was present in all facial primordia. Labeling indices
      were consistently higher in facial prominences than in midline tissues ventral to
      the brain. The results suggest that regional changes in cell densities could be
      used to reflect net changes in cell dispersion associated with altered balances
      between cell proliferation and extracellular matrix content in embryonic facial
      primordia.

PMID- 8288732
TI  - Proliferation of nasal epithelial and mesenchymal cells during primary palate
      formation.
AB  - Proliferation of nasal epithelial and mesenchymal cells in mouse embryos was
      analyzed during primary palate formation using immunohistochemical demonstration
      of the thymidine analogue, 5-bromodeoxyuridine. Pulse labeling was employed to
      determine cell proliferation rates, with cell density of the nasal mesenchyme
      also being measured. To represent the entire nasal groove and prominences, four
      levels along the superior-inferior direction of three regions were utilized,
      i.e., the lateral and medial nasal prominences (LNP and MNP) and the bottom of
      the nasal groove. During the formation period, the labeling indices of the LNP
      and MNP epithelium decreased with respect to the development stage, whereas those
      of the bottom epithelium only slightly did. The epithelial cells in the
      prospective fusion area particularly showed decreased DNA synthesis in comparison
      with those in the nonfusing areas. In addition, the corresponding activity in the
      presumptive fusion area of the LNP epithelium was less than that in the MNP
      epithelium. The time at which a definitive decrease in the labeling index of the
      presumptive fusion area is believed to occur between tail somite (TS) stages TS5
      7. A similar yet smaller decreasing tendency was observed in the labeling indices
      of the nasal mesenchyme. The cell density of the mesenchyme, however, slightly
      increased in all examined regions. Our results suggest that epithelial cell
      proliferation converts to a differentiation-type pattern, especially in the
      presumptive fusion area.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288734
TI  - Sex selection: why not?

PMID- 8288733
TI  - Arrest of amelogenin transcriptional activation in bromodeoxyuridine-treated
      developing mouse molars in vitro.
AB  - An important issue in craniofacial biology is understanding the molecular
      mechanisms that regulate the transcription of genes during development. Low
      concentrations of the thymidine analogue, 5-bromodeoxyuridine (BrdU), have been
      used to perturb transcription of tissue-specific genes in a variety of tissue
      types, although the molecular mechanism for this inhibition has not been
      elucidated. The purpose of the present study was to examine the following: (1) if
      amelogenin transcription is inhibited in mouse molars cultured in the presence of
      BrdU, (2) if changes in methylation patterns of the amelogenin gene can be
      detected with terminal differentiation of ameloblasts in vivo and in vitro; and
      (3) if changes in methylation patterns of the amelogenin gene can be detected in
      mouse molars cultured in the presence of BrdU. Northern blot hybridization and
      RNA phenotyping analysis revealed that bromodeoxyuridine (BrdU) incorporation
      into the DNA of developing mouse mandibular first molars (M1) in vitro inhibited
      amelogenin transcription. Restriction endonuclease digestion of M1 genomic DNA
      followed by Southern blot hybridization analysis revealed that amelogenin
      transcriptional activity in vivo and in vitro did not correlate with changes in
      methylation of the amelogenin gene. These results suggested that, unlike several
      other developmentally regulated genes, transcriptional regulation of the
      amelogenin gene may not be associated with changes in DNA methylation patterns.

PMID- 8288735
TI  - Rational approach to assisted fertilization.

PMID- 8288736
TI  - Diagnosis of sperm defects in selecting patients for assisted fertilization.

PMID- 8288737
TI  - Micro-assisted fertilization with human gametes.

PMID- 8288738
TI  - Use of assisted fertilization.

PMID- 8288739
TI  - Pentoxifylline: actions and applications in assisted reproduction.
AB  - Data are presented covering various studies on the use of the phosphodiesterase
      inhibitor pentoxifylline (PF) in the sperm preparation for procedures in assisted
      reproduction. Significant improvements have been shown in the fertilization rate
      of oocytes along with a reduced risk of failed fertilization cycles utilizing
      oligo/asthenozoospermic semen samples. Fertilization is also improved for
      normozoospermic samples when the acrosome reaction is suboptimal. PF has proven
      effects on sperm motility, increasing the proportion of hyperactivated
      spermatozoa. It can also enhance the acrosome reaction and this may be the more
      relevant function for clinical prediction. There is a further action as a
      suppressor or scavenger of reactive oxygen species although higher concentrations
      than that in current clinical use may be required to optimize this effect. PF
      should be washed out of the sample used for insemination to avoid inhibiting the
      completion of oocyte maturation.

PMID- 8288740
TI  - Improving the classification of endometriosis.

PMID- 8288741
TI  - The effect of flutamide on pulsatile gonadotrophin secretion in
      hyperandrogenaemic women.
AB  - The pulsatile gonadotrophin secretion in hyperandrogenaemic women was examined,
      following short-term androgen antagonism induced by flutamide, a specific
      androgen receptor blocker. Flutamide was administered to seven hyperandrogenaemic
      women and five normal cycling women, at a dose of 250 mg on the evening of day 1,
      followed by daily doses of 750 mg for 6 days. Blood samples were collected at 10
      min intervals for 8 h before (day 1) and during treatment (days 2 and 6).
      Gonadotrophin and prolactin concentrations were measured in all samples while sex
      hormone concentrations were analysed in selected samples. Flutamide
      administration to hyperandrogenaemic women was followed by a decrease in
      luteinizing hormone (LH) pulse amplitude (P < 0.05), associated with an apparent
      decline in mean LH concentrations. Follicle stimulating hormone (FSH) showed a
      significant fall after 6 days of treatment (P < 0.05). Total testosterone, free
      testosterone, androstenedione and dihydroepiandrosterone sulphate were
      significantly decreased during flutamide administration, while sex-hormone
      binding globulin and oestradiol were not affected. Normal women showed no
      significant changes in the above mentioned parameters. These results demonstrate
      that short-term androgen receptor blockade with flutamide reduces gonadotrophin
      secretion and androgen concentration in hyperandrogenaemic women. Since flutamide
      is devoid of intrinsic hormonal activity, it is suggested that the observed
      hormonal changes are secondary to the androgen blockade.

PMID- 8288742
TI  - Insulin-like growth factor-I stimulated growth and progesterone production by
      granulosa-lutein cells. Lack of interaction with physiological concentrations of
      luteinizing hormone and follicle stimulating hormone.
AB  - This study examined the effect of physiological concentrations of insulin-like
      growth factor-I (IGF-I), follicle stimulating hormone (FSH) and luteinizing
      hormone (LH) alone and in combination on growth and progesterone production by
      human granulosa-lutein cells. Granulosa-lutein cells were obtained from patients
      (n > 5) undergoing in-vitro fertilization (IVF) or gamete intra-Fallopian
      transfer (GIFT) treatment. Cells were cultured for 2 and 4 days in the presence
      of physiological concentrations of human LH (code 68/40, 5 IU/l), FSH (code
      83/575, 20 IU/l), or IGF-I (30 ng/ml) alone and in combination. Medium was
      changed every 2 days. No change in cell number (relative to each patient's own
      control) was observed after treatment with FSH or LH alone or in combination at
      any time. IGF-I alone produced a 117 +/- 8% and 176 +/- 15% (mean +/- SEM, n = 5)
      increase in cell number after 2 and 4 days respectively. This increase was
      unaffected by the addition of LH or FSH at any time. Basal progesterone secretion
      was variable (1633, 975-2409 nmol/l, median and interquartile range, day 2) and
      decreased with time in culture (564, 375-1089 nmol/l, day 4). After 2 days
      culture progesterone output increased by 116 +/- 5% of control in response to LH
      and 153 +/- 13% (mean +/- SEM, n = 5) of control in response to IGF-I. After 4
      days, LH and IGF-I stimulated progesterone levels by 279 +/- 52% and 264 +/- 37%
      (mean +/- SEM, n = 5) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288743
TI  - Melatonin potentiates testosterone-induced suppression of luteinizing hormone
      secretion in normal men.
AB  - A total of 12 healthy adult men were recruited to investigate the effect of
      exogenous melatonin on the sensitivity of the hypothalamo-pituitary axis to sex
      steroid negative feedback. The experiment consisted of a double-blind, randomized
      cross-over trial during which all subjects received 100 mg oral melatonin or
      placebo at 1600 h for 14 days. Midway through each of the two treatments (day 8),
      100 mg testosterone propionate i.m. (TP) was given at 0900 h. Blood samples for
      the measurement of luteinizing hormone (LH), follicle stimulating hormone (FSH),
      prolactin, testosterone and melatonin were taken at 0900 h on days 1, 3, 5, and
      daily from days 8-14. An additional blood sample was taken 8 h after the
      administration of testosterone. The interval between the melatonin and placebo
      treatment periods was 2 months. The oral administration of melatonin caused a
      pharmacological increase in the blood plasma concentration of melatonin which was
      maximum at 2 h and still above normal at 24 h. The daily treatment thus resulted
      in persistently high circulating levels of melatonin for 14 days. This treatment
      had no significant effect on the secretion of LH, FSH, prolactin or testosterone
      based on the first week of each study (melatonin compared with placebo). The
      injection of TP caused a rapid 3 to 4-fold increase in the plasma concentrations
      of testosterone which was at a maximum at 8 h and had returned to baseline within
      4 days, with a similar pattern in both the melatonin and placebo
      periods.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288744
TI  - Effects of recombinant human follicle stimulating hormone on cultured human
      granulosa cells: comparison with urinary gonadotrophins and actions in
      preovulatory follicles.
AB  - The effects of recombinant human follicle stimulating hormone (rFSH; Org 32489)
      have been examined in human granulosa cells from ovaries obtained from women with
      spontaneous menses. In the first series of experiments the actions of rFSH on
      production of oestradiol and progesterone were compared with those of urinary
      derived gonadotrophins. Recombinant FSH induced dose-dependent increases in
      production of both oestradiol and progesterone which were similar to the effects
      of 'pure' FSH (Metrodin) and the International Standard IS 71/223. In further
      studies, the actions of rFSH on oestradiol production by individual preovulatory
      follicles were investigated; rFSH increased oestradiol accumulation from cells
      obtained from follicles before the luteinizing hormone (LH) surge. In contrast,
      rFSH inhibited oestradiol production by granulosa cells derived from a follicle
      after the onset of the LH surge, whereas the gonadotrophic action of growth
      hormone was maintained. Following preliminary reports of the in-vivo effects of
      rFSH in women, these findings provide further validation of the efficacy of rFSH
      in the human ovary. The results of studies of the preovulatory follicle
      illustrate the experimental importance of the availability of recombinant
      preparations of pure gonadotrophins, produced by recombinant technology, in the
      understanding of human ovarian function.

PMID- 8288745
TI  - Physiological oestradiol and progesterone replacement cycles in women with
      ovarian failure: a model to study endometrial maturation and sex steroid receptor
      regulation by exogenous hormones.
AB  - High endometrial receptivity has been achieved with physiological oestradiol and
      progesterone replacement cycles in women with ovarian failure. To understand
      whether different protocols using the oral route or the transdermal route can
      influence the endometrial maturation and the regulation of sex steroid receptors,
      we studied 33 women with ovarian failure treated by two commonly used protocols
      and assessed endometrial receptivity using light microscopy, scanning electron
      microscopy and immunohistochemistry for oestrogen and progesterone receptors on
      biopsies taken to include different periods of the luteal phase. The morphology
      in these patients was similar to that observed in women with normal ovulatory
      cycles, indicating that the morphological response is not dependent on the type
      of oestradiol, oral or transdermal, in the replacement cycles as compared to the
      endogenous oestradiol in the menstrual cycle. The relative distribution of
      steroid receptors between the epithelium and stroma varies similarly to that
      observed during the luteal phase of the menstrual cycle. These results confirm
      the role of progesterone, especially the importance of the number of days of
      exposure to it, in the disappearance of steroid receptors from endometrial
      glands. These observations give a better understanding of endometrial receptivity
      around the time of presumed implantation and confirm clinical results concerning
      the best timing of oocyte transfer.

PMID- 8288746
TI  - Adverse local reaction to intramuscular injections of urinary-derived
      gonadotrophins.

PMID- 8288747
TI  - High concentrations of the soluble p55 tumour necrosis factor receptor in human
      seminal plasma.
AB  - Soluble TNFRs (tumour necrosis factor receptors) inhibit in-vivo and in-vitro
      bioactivities of TNF, and thus the secretion of soluble TNFRs could be a
      physiological principle to attenuate the bioactivities of TNF. Two types of TNFR
      have been identified and both forms can be released from cells. In this study,
      soluble TNFRs in seminal plasma from three groups of men were analysed: from men
      with normal semen quality (n = 32), with reduced semen quality (n = 7) and
      vasectomized men (n = 3). Sensitive and specific enzyme-linked immunosorbent
      assays were utilized to detect soluble TNFRs in seminal plasma, based on capture
      antibodies directed against non-TNF-binding sites of the TNFRs and digoxigenin
      (DIG)-labelled TNF. The mean +/- standard deviation levels of p55 TNFR were 56.4
      +/- 20, 64.4 +/- 17 and 45.4 +/- 5 ng/ml in the three groups, respectively. The
      concentration of p75 TNFR was < 1 ng/ml in all groups. The results suggest an
      exclusive existence of high amounts of the soluble p55 TNFR in seminal plasma.
      Seminal plasma from vasectomized men contained p55 TNFR at approximately the same
      levels as the specimen from the two other groups, indicating that the source of
      p55 TNFR is not the testis but rather some tissue more distal in the male genital
      tract, such as the prostate or the seminal vesicles. The soluble p55 TNFR was
      purified from human seminal plasma, using affinity and gel filtration
      chromatography. Further characterization of the purified p55 revealed a protein
      with a molecular weight of approximately 22 kDa, both under reducing and non
      reducing conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288748
TI  - Prognostic significance of maternal DR histocompatibility types in Danish women
      with recurrent miscarriages.
AB  - In a previous case-control study of women with unexplained recurrent miscarriages
      we reported that the frequency of women positive for each of the two
      histocompatibility (HLA) types HLA-DR1, Br and HLA-DR3 was increased in a subset
      of patients with a history of four or more miscarriages. In the present study we
      examined whether the increased frequency of the two HLA types in this subset of
      patients indicated that they would result in a poor pregnancy prognosis. We
      related pregnancy outcomes to the mothers' HLA-DR type in a prospective study of
      a well-defined, closely supervised group of 94 women with unexplained recurrent
      miscarriages who had achieved intra-uterine pregnancy in the course of one of two
      prospective placebo-controlled trials concerning the efficacy of immunotherapy.
      Of the patients who were HLA-DR1, Br and/or HLA-DR3 positive 62% miscarried their
      next pregnancy compared with 29% of the patients negative for the two HLA types
      [relative risk of miscarriage in the former group = 2.2 (P < 0.002) unadjusted,
      and 1.8 (P = 0.025) when adjusted for the number of previous miscarriages]. The
      results suggest that Danish women with unexplained recurrent miscarriages who are
      positive for HLA-DR1, Br and/or -DR3 display a poorer pregnancy outcome than
      patients negative for these types.

PMID- 8288749
TI  - A simple, non-invasive method of Fallopian tube sperm perfusion.
AB  - This case report describes a simple non-invasive method of Fallopian tube sperm
      perfusion using a paediatric Foley catheter, which does not require cannulation
      of the Fallopian tube and can be performed on an outpatient basis. The patient
      achieved an intra-uterine pregnancy with demonstrable fetal heart beats.
      Subsequently, use of this method in 29 treatment cycles in 14 women with
      unexplained infertility has resulted in six singleton and one twin ongoing
      clinical pregnancies.

PMID- 8288750
TI  - Repeat trials of oocyte donation to women with previous donor oocyte success.
AB  - Oocyte donation has proven to be highly successful in establishing pregnancy in
      functionally agonadal women. Both implantation and ongoing pregnancy rates in
      women using this method have surpassed those normally seen in standard in-vitro
      fertilization (IVF) patients. Over a 5 year period, seven women who had
      previously conceived using oocyte donation elected to attempt pregnancy and
      deliver a second child using the same donor. In each case the paramount
      consideration was to provide a sibling of the same genetic make-up as the child
      or children previously borne. Of the seven women studied, whose ages ranged from
      24 to 44 years, five became pregnant on subsequent cycles. The time to conception
      varied from one to a maximum of three attempts with three of the five women
      becoming pregnant on the first cycle and two requiring three cycles to establish
      the subsequent pregnancy. The overall rate of success in this group was 12
      pregnancies in 20 cycles of embryo transfer (60%). An exaggerated implantation
      rate (25.6%) was also noted (23 individual embryo implantations from 90 embryos
      transferred). Of the 12 pregnancies established in these seven women, four (33%)
      were multiple gestations (three triplets, one twin). We conclude that women who
      have previously experienced pregnancy following oocyte donation are highly likely
      to conceive in a subsequent trial at a rate that may be higher than that normally
      seen in the general population of women undergoing oocyte donation.

PMID- 8288751
TI  - An auto-controlled study in in-vitro fertilization reveals the benefit of Percoll
      centrifugation to swim-up in the preparation of poor-quality semen.
AB  - The efficiency of spermatozoa prepared by swim-up or by Percoll centrifugation
      was assessed in an in-vitro fertilization programme on 71 semen samples of a well
      defined quality [total number of type A (WHO criteria) motile spermatozoa]:
      category I (n = 21) with > 100 x 10(6), II (n = 31) with 15-100 x 10(6), III (n =
      11) with 5-15 x 10(6) and IV (n = 8) with < 5 x 10(6) type A motile spermatozoa.
      Oocytes were inseminated 4 h after oocyte retrieval, alternately with spermatozoa
      derived from swim-up and Percoll preparation. Both selection procedures resulted
      in a significantly higher (P < 0.001) percentage motility as compared to fresh
      semen. For low-quality samples (III and IV), however, swim-up was more effective
      in selecting highly motile (P = 0.004) and morphologically normal spermatozoa (P
      < 0.05). For high-quality samples, this difference might have been masked by
      introducing a swim-up step to remove Percoll particles. Regardless of the initial
      sperm quality, the mean fertilization rate was significantly higher (P = 0.003)
      when Percoll-treated spermatozoa were used for insemination (51.3 versus 37.8%).
      For semen of groups I and II, no difference in fertilization capacity was
      observed according to the sperm preparation method. Despite the lower percentage
      motility and normal morphology for the Percoll compared to the swim-up treatment
      in groups III and IV, fertilizing capacity was significantly (P < 0.001) in
      favour of this selection method (65.3 versus 26.5% in group III, 47.6 versus
      11.6% in group IV).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288752
TI  - Mitochondrial disease and reduced sperm motility.
AB  - Mitochondrial dysfunction reduces aerobic energy production and results in
      symptoms from various tissues, depending on metabolic demands. Mitochondrial
      adenosine triphosphate (ATP) is essential for sperm motility. Sperm motility was
      investigated in a patient with a mitochondrial disease caused by reduced activity
      of the mitochondrial enzyme complexes I and IV, and in two control subjects.
      Spermatozoa were cultured in media containing various energy substrates. Motility
      was judged by light microscopy, and ultrastructure by transmission electron
      microscopy. In the patient with mitochondrial disease, 12% of the spermatozoa
      were motile in the medium containing only glucose. There was a three-fold
      increase in motile spermatozoa when pyruvate and succinate were present together
      with glucose. In contrast, the spermatozoa of both control subjects had best
      motility in the presence of substrates for complex I, and no further increase was
      observed when succinate was added. Glucose and pyruvate enter the respiratory
      chain at complex I, and succinate at complex II. Electron microscopy of
      spermatozoa from the patient with mitochondrial disease revealed mitochondria
      with increased matrix, thickening of membranes, parallelization of cristae and
      lipid inclusions, which are characteristic findings in mitochondrial disorders.
      Abnormal mitochondria were also found in a spermatid, suggesting that the
      ultrastructural changes of mitochondria are primary rather than secondary to
      degeneration of the spermatozoa. The results indicate that mitochondrial
      dysfunction causes reduced sperm motility in some men.

PMID- 8288753
TI  - Effect of growth hormone administration on circulating levels of luteinizing
      hormone, follicle stimulating hormone and testosterone in normal healthy men.
AB  - A new area of growth hormone (GH) therapy in adults is the treatment of
      infertility. The aim of this study was to evaluate the effects of pharmacological
      GH administration on the secretion of pituitary and gonadal hormones in normal
      men. Eight healthy men, 23-32 years of age (mean 28.1 years), with a normal body
      mass index were studied in a double-blind, placebo-controlled crossover design.
      All participants had a normal semen analysis before entering the study. Each
      participant was treated with placebo and GH (12/IU/day, Norditropin; Novo
      Nordisk, Denmark) during two different 14-day periods, separated by a 6 week
      washout period. Administration of GH for 14 days resulted in a significant
      increase in serum insulin-like growth factor I (IGF-I; P < 0.01) but no changes
      occurred in IGF-I values during placebo treatment. The concentrations of follicle
      stimulating hormone and luteinizing hormone displayed no change during the two
      periods and did not differ between the GH treatment period and the placebo
      period. The concentration of testosterone was unchanged during the placebo/GH
      periods and there was no difference between the GH treatment period and the
      placebo period. We conclude that GH treatment for 14 days in normal healthy men
      does not affect gonadotrophin or testosterone patterns.

PMID- 8288754
TI  - Assessment of the acrosomal status and viability of human spermatozoa
      simultaneously using flow cytometry.
AB  - Acrosomal status and viability were evaluated simultaneously on human spermatozoa
      using flow cytometry. Samples were divided into three aliquots and randomly
      assigned to one of three treatments: (i) cryopreservation; (ii) 10 microM calcium
      ionophore [A23187 in dimethylsulphoxide (DMSO)] or (iii) DMSO alone (control).
      Acrosomal status was evaluated using monoclonal antibodies recognizing MH61 and
      CD46, respectively. Fluorescein-conjugated goat anti-mouse immunoglobulin (IgG)
      was used as a second antibody. Sperm viability was assessed using Hoechst 33258
      (H258) exclusion. The following factors were analysed: (i) the specificity of the
      monoclonal antibodies for the human acrosome; (ii) the relative effectiveness of
      flow cytometry and direct fluorescent microscopy scoring and (iii) the acrosomal
      status and viability of the control, ionophore-treated, and cryopreserved
      spermatozoa. Across all treatments, the MH61 and CD46 monoclonal antibodies
      resulted in acrosomal status values (acrosome-reacted/viable spermatozoa) which
      were not significantly different (P > 0.05): control, 1.0 +/- 0.3% and 1.5 +/-
      0.6% (mean +/- SEM); A23187, 42.8 +/- 3.5% and 38.1 +/- 3.5%; cryopreserved, 8.2
      +/- 2.0% and 9.9 +/- 1.3%; respectively. However, acrosomal status among
      treatments differed significantly (P < 0.01). Flow cytometric and direct
      fluorescent microscopy assessments were significantly correlated (r2 = 0.96, P <
      0.01). These results indicate that flow cytometry, using an acrosome-specific
      monoclonal antibody and a supravital dye, provides an objective and efficient
      method to evaluate human sperm acrosomal and viability status simultaneously.

PMID- 8288755
TI  - The effect of sperm preparation methods on the fertilization rate of oocytes
      micro-inseminated by subzonal sperm injection.
AB  - Three methods were used to prepare spermatozoa for subzonal injection into mature
      oocytes. In method A, the washed sperm suspension was incubated for 18 h in
      modified T6 culture medium. Method B consisted of incubating the sperm suspension
      for 6 h in regular T6 culture medium. In method C, the sperm suspension was
      incubated for 6 h in regular T6 culture medium containing 20% (v/v) follicular
      fluid. The percentages of acrosome-free spermatozoa and fertilization rates were
      compared for 42 treatment cycles assigned randomly to the three sperm preparation
      methods. The sperm suspensions prepared by methods A and C each had significantly
      higher proportions of acrosome-free spermatozoa compared to suspensions prepared
      by method B. The fertilization rates of oocytes micro-injected with spermatozoa
      prepared by methods A and C were significantly higher than for method B. Eight
      clinical pregnancies resulted from 28 cycles in which embryo replacement
      occurred. We conclude that the fertilization rate following subzonal sperm
      injection is related directly to the percentage of acrosome-free spermatozoa in
      the sperm suspension used for microinjection.

PMID- 8288756
TI  - Tripronuclear human zygotes: the first cell cycle and subsequent development.
AB  - About 6.6% of human oocytes fertilized in vitro were tripronuclear. The first
      cell cycle and developmental ability of these triploid zygotes were studied by
      autoradiographic analysis of pronuclear [3H]thymidine incorporation and by
      morphological observations of living zygotes at various times after insemination.
      Weak labelling over the pronuclei was first detected at 10 h after insemination
      and in many zygotes the pronuclei were heavily saturated with radioactive grains
      by 11-13 h. Thymidine incorporation was not apparent in the majority of
      tripronuclear zygotes by 21-22 h. At this time, 96% of living triploids (65/68)
      had visible pronuclei while the others entered the first mitosis and their
      pronuclei disappeared. By 25 h, 70% of triploid zygotes (37/58) still exhibited
      visible pronuclei and 26% were already in mitosis. The first divided embryos were
      seen by 25 h. The results suggest that the length of the complete cell cycle of
      human 1-cell stage triploids is approximately 25 h. Pronuclear DNA synthesis
      starts approximately 9-10 h after insemination and seems to last a minimum of 4 h
      (the precise time of S phase could not be determined). The minimal duration times
      of G2 phase and mitosis are estimated in the range of 4-6 h and 3.5-4 h,
      respectively. Tripronuclear zygotes were capable of substantial in-vitro
      development. About half of examined triploids attained at least the 4-6-cell
      stage of development (14/32; 44%); however, approximately 19% of these exhibited
      multinuclear cells. The remaining triploids had reached early morula (8 and 13
      cells; 25 and 19%) or blastocyst (6%) stage.

PMID- 8288757
TI  - Polypeptide profiles of human oocytes and preimplantation embryos.
AB  - The polypeptides that direct fertilization and early development until activation
      of the embryonic genome occurs, at the 4-8 cell stage in the human, are
      exclusively maternal in origin, and are either synthesized during oogenesis or
      translated later from maternal mRNA. Using sodium dodecyl sulphate-polyacrylamide
      gel electrophoresis and silver stain, we have visualized and compared the
      polypeptides present in different populations of human oocytes and cleavage stage
      embryos obtained after superovulation and insemination in vitro. Two polypeptide
      patterns were resolved, differing in the region of mol. wt 69 kDa. The
      distribution of these patterns showed no correlation with the ability of
      individual oocytes to achieve fertilization and develop normally to the 8-cell
      stage.

PMID- 8288758
TI  - Blood analysis of mice born following single-cell embryo biopsy.
AB  - Single-cell embryo biopsy is an important technique in preimplantation diagnosis.
      The development of the mouse embryo and fetus, and the results of some analyses
      after birth following embryo biopsy, have been demonstrated to be normal.
      Histopathological analysis of mice born following single-cell embryo biopsy with
      a physical method (zona puncture) also showed normal organ and cell structure,
      thus demonstrating the safety of embryo biopsy. This experiment analysed the
      parameters of blood cells and the blood chemistry of 28 mice born following
      single-cell embryo biopsy. White cell count, red cell count, haemoglobin level
      and platelet count of the blood, and plasma sodium, potassium, chloride,
      bicarbonate, calcium, glucose, albumin, protein, creatinine, urea, bilirubin,
      aspartate transaminase, creatine kinase and lactate dehydrogenase of the blood
      were not significantly different between the mice from the biopsied and the
      control embryo groups, which again demonstrated the safety of single-cell embryo
      biopsy. The remaining totipotent cells in the biopsied embryos would thus be
      expected to develop to the correct cell counts and normal organic functions
      according to the intact hereditary messages. Further studies on the safety of
      embryo biopsy (including long-term observation after birth) and the improvement
      of the different biopsy techniques and skills for preimplantation diagnosis are
      necessary.

PMID- 8288759
TI  - Radionuclide migration through the genital tract in infertile women with
      endometriosis.
AB  - The migration of radionuclide through the genital tract was observed, comparing
      20 patients with endometriosis and infertility with a control group of 23
      infertile patients who had a normal pelvis. All patients had patent tubes at
      laparoscopy and chromopertubation, performed in both groups for the investigation
      of infertility and to diagnose the presence and extent of endometriosis. A
      radionuclide tubal test, using human albumin microspheres labelled with 99m
      technetium (99mTc) was subsequently undertaken to observe the extent of genital
      tract migration of radionuclide to uterus, Fallopian tube and peritoneal cavity.
      The results show that radionuclide migration to the peritoneal cavity was
      impaired in patients with endometriosis, compared with the control group (30
      versus 83%, respectively; P < 0.001). There was no relationship between migration
      and the severity of endometriosis. We conclude that impaired tubal function may
      be a cause of infertility in some patients with endometriosis.

PMID- 8288760
TI  - Immunohistochemical analysis of oestrogen and progesterone receptors in
      endometriotic tissue and endometrium.
AB  - The objective of the study was to compare the localization and staining intensity
      of oestrogen and progesterone receptors in endometrium and endometriotic tissue.
      Using monoclonal antibodies towards oestrogen and progesterone receptors,
      analysis was performed in 63 endometriotic samples from 40 women and compared to
      endometrium obtained simultaneously from 25 of the women. Using a staining index,
      'total immuno-staining score', calculated from the staining intensity multiplied
      by the fraction of positive cells, the receptor content was estimated
      semiquantitatively. The scores for both oestrogen and progesterone receptors were
      lower in endometriotic epithelial cells than in endometrial epithelial cells, but
      the differences reached statistical significance only for the progesterone
      receptor. No difference was found for stromal cells. There was a significant
      correlation between oestrogen receptor score in endometriotic tissue and in
      endometrium, but not for progesterone receptor score. In endometrium and vaginal
      and peritoneal endometriosis, the progesterone receptor score showed similar
      values, higher than those in ovarian endometriosis. The data from this large
      immunohistochemical study support previous results of quantitative steroid
      receptor analyses, indicating that the regulation of steroid effects, especially
      those of progesterone, differs between endometriotic and endometrial tissue.

PMID- 8288761
TI  - The correlation of placental protein 14 concentrations in uterine flushing and
      endometrial morphology in the peri-implantation period.
AB  - The relationship between the concentrations of placental protein 14 (PP14) in
      uterine flushing and the endometrial morphology in the mid-luteal phase was
      assessed in a prospectively designed study involving the precise timing of all
      samples by the luteinizing hormone (LH) surge. A total of 29 regularly cycling
      women with unexplained infertility or recurrent miscarriage were studied. To
      flush the uterine cavity, 10 ml of physiological saline solution was used
      immediately prior to sampling of an endometrial specimen for morphological study,
      in the mid-luteal phase. PP14 concentrations were measured by radioimmunoassay in
      uterine flushings and plasma samples; the endometrium was assessed by the use of
      histological dating criteria and morphometric techniques. PP14 levels in uterine
      flushings were correlated with endometrial dating and volume fraction measurement
      of the glands. They were consistently below the sensitivity of the assay with
      histological dating of < day LH +5, or when the glandular lumen occupied < 20% of
      the gland. In contrast, PP14 concentrations in plasma were not related to
      histological dating or morphometric analyses, and did not differ in patients with
      normal endometrial development (20.8 ng/ml) and in those with retarded
      endometrial development (22.5 ng/ml). The presence of detectable concentrations
      of PP14 in uterine flushing was significantly associated with normal histological
      dating. Uterine flushing may therefore provide a reliable, non-invasive
      alternative to endometrial biopsy in the evaluation of endometrial function in
      the peri-implantation period.

PMID- 8288762
TI  - Function of the corpus luteum, the endometrium and the trophoblast after
      treatment of tubal pregnancy by prostaglandin F2 alpha.
AB  - The activity of the corpus luteum, the endometrium and the trophoblast was
      studied after local medical treatment of 31 women with tubal pregnancy. We
      measured the serum concentration of progesterone, the secretory endometrial
      protein placental protein 14 (PP14), and human chorionic gonadotrophin (HCG)
      before and after treatment by injection of prostaglandin F2 alpha into the site
      of the gestation and into the corpus luteum. There was no significant difference
      in the pre-treatment serum progesterone and serum PP14 concentrations of 26 women
      who were treated successfully and of five women, who were operated on after
      failure of the treatment. After the prostaglandin treatment the serum
      progesterone and PP14 concentrations decreased simultaneously with the serum HCG
      concentration or remained at a low, constant concentration. We conclude that
      measurement of serum progesterone and PP14 cannot be used for selection of
      patients for treatment by prostaglandin F2 alpha or for monitoring the effect of
      the treatment. The injection of prostaglandin into the ovary has either no effect
      on the activity of the corpus luteum or induces only a partial luteolysis.

PMID- 8288763
TI  - Transvaginal crown-rump length measurements of 224 successful pregnancies which
      resulted from gamete intra-Fallopian transfer or in-vitro fertilization.
AB  - The crown-rump lengths (CRL) of 224 pregnancies which resulted from gamete intra
      Fallopian transfer (GIFT) or in-vitro fertilization (IVF) were assessed two to
      four times in the first trimester. The results were compared with some of the
      published articles which assessed CRL in spontaneous and induced pregnancies. The
      range of CRL measurements from this study was generally smaller than the
      previously published data, although all women went on to deliver normal fetuses
      at full term weighing > 2.5 kg. It was not possible to identify a clear reason
      for this finding, but factors which might have been relevant included population
      differences, more accurate estimation of ovulation/conception time, the exclusive
      use of vaginal ultrasonography in this study and variations in the embryonic
      implantation/development times. There is a need to review the commonly used CRL
      charts in view of the increasing use of transvaginal ultrasonography and the
      increasing number of pregnancies with known ovulation/conception times. Each
      centre should aim to establish the normal CRL range for its own population.

PMID- 8288764
TI  - Pregnancy and implantation rates in normal replacement versus stimulated cycles.
AB  - The relative importance that endometrial development and embryo quality have on
      implantation rates achieved with assisted reproductive technology (ART) is the
      subject of controversy. Ovarian stimulation has been repeatedly mentioned as
      having a detrimental effect on endometrial receptivity (Paulson et al., 1990,
      Fertil. Steril., 53, 870-874). We compared pregnancy and implantation rates
      achieved with ART during stimulated cycles and hormonal replacement cycles, in
      patients matched for the following criteria: age < 35 years for the patient
      donating oocytes; transfer of at least two good quality embryos/oocytes and good
      quality transfer. All transfer cases performed during hormonal replacement cycles
      were done with donated oocytes. Comparison of results between techniques was not
      attempted due to potential differences in populations. The pregnancy and
      implantation rates achieved with each technique during stimulated and hormonal
      replacement cycles were not statistically different. In contradiction to previous
      results, our data suggest that differences in uterine receptivity between
      stimulated and hormonal replacement cycles in the age group studied are not of
      critical importance in embryo implantation. Good embryo quality appears to be the
      dominant factor in determining the success of ART.

PMID- 8288765
TI  - Effect of pentoxifylline on implantation and post-implantation development of
      mouse embryos in vitro.
AB  - Previous work from our laboratory has revealed that brief exposure of mouse
      zygotes to 3.6 and 7.2 mM pentoxifylline reduced cell numbers in mouse embryos
      reaching the blastocyst stage in vitro. Since a decrease in cell numbers may
      impair further development, the present study aimed to assess the implantation in
      vitro and the development beyond implantation of these embryos. Blastocysts
      cultured from the one-cell stage in the presence of 5, 10 and 50 microM
      pentoxifylline, i.e. concentrations expected in the secretions of the genital
      tract after oral administration, were shown to develop normally to the egg
      cylinder stage in vitro. Blastocysts, obtained after culture in vitro of zygotes
      exposed approximately 29 h after human chorionic gonadotrophin (HCG) for 30 min
      to 3.6 and 7.2 mM pentoxifylline, i.e. the concentrations used for enhancing
      sperm function in vitro, could implant but their development to the egg cylinder
      stage was found to be impaired. The same effect was noticed if blastocysts, grown
      in vitro from the one-cell stage, were exposed to 3.6 and 7.2 mM pentoxifylline
      for 30 min in vitro approximately 120 h after HCG. These findings imply that when
      pentoxifylline is used to enhance sperm function in vitro, it should be washed
      out of the preparation used for insemination.

PMID- 8288766
TI  - A survey of parental attitudes toward oocyte donation.
AB  - A questionnaire was sent to couples who had successfully completed oocyte
      donation cycles to survey their experiences and make suggestions to others
      considering this option. A majority of couples were successful in their first
      cycle, despite advanced maternal age or length of time attempting conception. A
      preference for non-anonymous arrangements was highlighted, despite the unknown
      long-term impact, and the importance of finding support was stressed. Respondents
      indicated no confusion about their role as parents of children conceived through
      oocyte donation.

PMID- 8288767
TI  - Curing the human embryo--curing the placenta.

PMID- 8288768
TI  - Genetic disorders: methods of avoiding the birth of an affected child.

PMID- 8288769
TI  - Secondary olfactory projections and pallial topography in the Pacific hagfish,
      Eptatretus stouti.
AB  - The extent of the secondary olfactory projections shows great variation among
      different groups of craniates. Gnathostomes typically display restricted
      secondary olfactory projections, whereas lampreys have more extensive
      projections. Any attempt to determine the phylogenetic polarity of these
      characters, that is, to decide which is primitive and which is derived, requires
      an investigation of the secondary olfactory system in the sister group of
      lampreys and gnathostomes, the hagfishes. Therefore the secondary olfactory
      projections of the Pacific hagfish, Eptatretus stouti, were traced with the use
      of horseradish peroxidase and the lipophilic fluorescent tracing compound DiI.
      The projections are bilateral and massive to all pallial areas and the septum,
      moderate to the striatum, and relatively weak to the preoptic and infundibular
      regions of the hypothalamus, reaching caudally to the diencephalic-mesencephalic
      boundary. Afferents to the olfactory bulb arise from the pallium, the preoptic
      area, and the ventral thalamus. We compare the secondary olfactory projections in
      hagfishes with those in lampreys and in gnathostomes, and we conclude that the
      presence of extensive secondary olfactory projections is a primitive character of
      craniate brains.

PMID- 8288770
TI  - Distribution and characterization of tumor necrosis factor-alpha-like
      immunoreactivity in the murine central nervous system.
AB  - Tumor necrosis factor-alpha (TNF alpha) is a protein released from macrophages
      during infection and inflammation. Recent studies suggest that it has several
      effects within the central nervous system, including generation of fever,
      enhancement of slow wave sleep, and stimulation of pituitary hormone secretion.
      We have proposed that TNF alpha may be synthesized by neurons in the CNS and used
      as a neuromodulator in the pathways involved in the central control of these
      activities. To test this hypothesis, we have used an antiserum raised against
      recombinant murine (rm) TNF alpha with an indirect immunoperoxidase technique to
      stain the murine CNS immunohistochemically. Western blot analysis of mouse brain
      homogenates revealed one band with electrophoretic mobility identical to that of
      rmTNF alpha. We identified TNF alpha-like immunoreactive (ir) neurons in the
      hypothalamus, in the bed nucleus of the stria terminalis, in the caudal raphe
      nuclei, and along the ventral pontine and medullary surface. TNF alpha ir
      innervation was widespread within the CNS, particularly in areas involved in
      autonomic and endocrine regulation, including the hypothalamus, amygdala, bed
      nucleus of the stria terminalis, parabrachial nucleus, dorsal vagal complex,
      nucleus ambiguus, and thoracic sympathetic preganglionic cell column. Our data
      suggest that TNF alpha may serve as a neuromodulator in central pathways involved
      in the regulation of the autonomic, endocrine and behavioral components of the
      acute-phase response to inflammation and infection.

PMID- 8288771
TI  - Comparative distribution of mammalian GnRH (gonadotrophin-releasing hormone) and
      chicken GnRH-II in the brain of the immature Siberian sturgeon (Acipenser baeri).
AB  - The brain of the sturgeon has recently been shown to contain at least two forms
      of GnRH (gonadotropin-releasing hormone), mammalian GnRH (mGnRH) and chicken GnRH
      II (cGnRH-II). In this study, we compared the distribution of immunoreactive (ir)
      mGnRH and cGnRH-II in the brain of immature Siberian sturgeons (Acipenser baeri).
      The overall distribution of mGnRH was very similar to the distribution of sGnRH
      in teleosts such as salmonids or cyprinids. mGnRH-ir perikarya were observed in
      the olfactory nerves and bulbs the telencephalon, the preoptic region, and the
      mediobasal hypothalamus. All these cell bodies are located along a continuum of
      ir-fibers that could be traced from the olfactory nerve to the
      hypothalamopituitary interface. No ir-fibers were observed in the anterior lobe
      of the pituitary, but a few were seen to enter the neurointermediate lobe. mGnRH
      ir fibers were detected in many parts of the brain, particularly in the
      forebrain. mGnRH-ir cerebrospinal fluid-contacting cells were observed in the
      telencephalon, the preoptic region, and the mediobasal hypothalamus. In contrast,
      cGnRH-II was present mainly in the posterior brain, although a few ir axons were
      seen in the above-mentioned territories. In particular, cGnRH-II-ir cells bodies,
      negative for mGnRH, were consistently observed in the nucleus of the medial
      longitudinal fasciculus of the midbrain tegmentum. The cGnRH-II innervation in
      the optic tectum, cerebellum, vagal lobe, and medulla oblongata was more abundant
      than the mGnRH innervation in the same areas. This study provides evidence that
      the organization of the GnRH systems in a primitive bony fish is highly similar
      to that reported in teleosts and further documents the differential distribution
      of two forms of GnRH in the brain of vertebrates.

PMID- 8288772
TI  - Physiology and morphology of spiking local interneurons in the terminal abdominal
      ganglion of the crayfish.
AB  - Not only nonspiking local interneurons but also spiking local interneurons in the
      terminal abdominal ganglion of the crayfish (Procambarus clarkii Girard)
      contribute to form the motor output of the uropod. In this study, 14 spiking
      local interneurons are identified by their gross morphology and physiological
      properties including the sensory inputs from the uropod and premotor output onto
      the uropod motor neurons on both sides. Morphologically, they are divided into
      three groups based on the position of their somata: anterior, medial, and
      posterior. The main branches of interneurons in each group are usually extended
      on the side contralateral to the soma, or they have profuse bilateral branches.
      Physiologically, all of them receive excitatory inputs from the afferents
      innervating the exopodite on the side ipsilateral their main branches. They are
      usually silent, and spike only in response to sensory stimulation. The majority
      of them (11 out of 14 neurons) have output effects on the uropod motor neurons
      that elicit reciprocally closing pattern. They increased the activity of the
      closer motor neurons and decreased the activity of the opener motor neurons. Only
      one interneuron inhibits the closer motor neurons. The remaining two interneurons
      coactivate both the antagonistic motor neurons. Since the reciprocal closing
      pattern of the uropod motor neurons is elicited in response to sensory
      stimulation of the uropod, spiking local interneurons may initiate this local
      reflex circuit. They detect the initiation of the stimulus and convey signals
      from the sensory to the motor side.

PMID- 8288773
TI  - Fiber pathways and branching patterns of biocytin-labeled olivocochlear neurons
      in the mouse brainstem.
AB  - Olivocochlear neurons have somata in the superior olivary complex in the
      brainstem and project fibers to the cochlea. The purpose of the present study was
      to demonstrate the fiber pathways and branching patterns of olivocochlear fibers
      within the brainstem. Olivocochlear fibers were labeled by extracellular
      injections of biocytin into the cochlea of mice. The injections labeled two
      populations of olivocochlear fibers. Thin olivocochlear fibers arose from small
      somata of the lateral olivocochlear group located ipsilaterally in the lateral
      superior olive. Thick olivocochlear fibers arose from larger somata of the medial
      olivocochlear group located bilaterally in the periolivary nuclei. The lateral
      olivocochlear and medial olivocochlear fibers had similar courses but differed in
      their branching patterns. Branches from lateral olivocochlear fibers terminated
      near their somata of origin in the lateral superior olive or in the lateral
      vestibular nucleus. Branches from medial olivocochlear fibers terminated in the
      inferior vestibular nucleus or in the cochlear nuclear complex. A few branches
      from medial olivocochlear fibers projected to the contralateral side. Although
      they project primarily to the cochlea, olivocochlear neurons also give off
      branches to a variety of nuclei in the brainstem, thus involving auditory and non
      auditory nuclei in the olivocochlear reflex system.

PMID- 8288774
TI  - Dendritic domains of medium spiny neurons in the primate striatum: relationships
      to striosomal borders.
AB  - Medium spiny neurons are the projection neurons of the striatum. They receive the
      majority of striatal afferents, and they make up the vast majority of all neurons
      in the striatum. These densely spiny cells thus constitute a major substrate for
      input-output processing in the striatum. In the experiments described here we
      analyzed the dendritic fields of spiny neurons in the squirrel monkey striatum
      and plotted their orientations with respect to the borders between striosomes and
      matrix. Medium-sized spiny neurons in the caudate nucleus were filled
      intracellularly in a fixed-slice preparation with the fluorescent dye Lucifer
      Yellow. Dendritic arbors were reconstructed following immunostaining of the
      injected neurons with antiserum to Lucifer Yellow and counterstaining for
      striosome/matrix compartments. A majority of the medium spiny neurons studied had
      dendritic arborizations that remained within their compartment of origin. Thus
      the striosome/matrix subdivision not only partitions neurotransmitter molecules
      and extrinsic striatal connections into two domains in the primate caudate
      nucleus, but also constrains the dendritic arbors of many projection neurons
      there. Other medium spiny neurons, however, in both striosomes and matrix, had
      dendrites that crossed from one compartment into the other. About a quarter of
      the spiny neurons reconstructed had at least one such crossing dendrite. These
      results suggest that compartmentalization of afferent and efferent processing by
      projection neurons in the primate striatum is not absolute. For a subpopulation
      of spiny neurons in striosomes and matrix, inputs to one compartment could have a
      direct influence on output cells of the other.

PMID- 8288775
TI  - Dendritic arbors of spiny neurons in the primate striatum are directionally
      polarized.
AB  - Despite the relatively unfeatured cytoarchitecture of the striatum, this large
      subcortical region has been found to have a modular macroscopic substructure
      comprising the neurochemically distinct striosomes and matrix, and, within the
      matrix, patchy input and output arrangements called matrisomes. In the study
      reported here, we explored the possibility that the cellular architecture of the
      striatum is also more specialized than previously suspected. We injected medium
      spiny neurons in lightly fixed slices of the squirrel monkey caudate nucleus,
      reconstructed their dendritic arbors, and analyzed the orientations of these
      arbors with respect to the cardinal planes of the striatum. The data were
      unequivocal in suggesting that many spiny neurons, whether near striosomes or
      not, have dendritic arbors with preferred orientations along a diagonal axis
      running from rostral, dorsal, and medial to caudal, ventral, and lateral. This
      axis corresponds to the orientations of many striosomes and matrisomes in the
      squirrel monkey's caudate nucleus. We therefore suggest that the primate striatum
      is characterized not only by a macroscopic organization dividing it into
      striosomes and matrisomes, but also by a microscopic architecture observed by the
      dendritic arbors of many of its projection neurons. We obtained comparable
      supplementary observations for the ferret caudate nucleus, suggesting that such
      spatial alignment of spiny dendritic arbors may be a general feature of striatal
      organization. These polarized dendritic arrangements could provide a cellular
      framework for compartmental input-output processing within the striatum.

PMID- 8288776
TI  - Stathmin: cellular localization of a major phosphoprotein in the adult rat and
      human CNS.
AB  - Stathmin is a ubiquitous, 19 kDa cytoplasmic protein the phosphorylation of which
      is associated with many cellular signaling pathways. It is particularly abundant
      in neurons and reaches a peak of expression in the neonatal period, although it
      remains highly expressed in the adult brain. In order to determine whether this
      abundant expression is associated with discrete cellular populations that are
      still at an immature stage during adulthood, as suggested by others, the cellular
      localization of stathmin was investigated in the adult rat and human central
      nervous system. Western blotting with a specific antiserum indicated that
      stathmin was ubiquitous in the brain and spinal cord but that its relative
      concentration varied up to 2.6 times between regions. To characterize the
      distribution of stathmin within the brain, its cellular localization was analyzed
      by immunocytochemistry. Highly immunoreactive neurons and oligodendrocytes were
      observed, and stathmin immunoreactivity was localized to the perikaryon and all
      processes, but not the nucleus. Most brain and spinal cord cell groups showed
      stathmin immunoreactivity, although the extent and intensity of labeling differed
      largely from one place to another. Particularly numerous stathmin-immunoreactive
      neuronal cell bodies were found in the pyriform, cingulate, and neocortex, as
      well as in many cholinergic nuclei of the basal forebrain and brainstem, in the
      medial thalamus, in various brainstem nuclei, in the dorsalmost layers of the
      spinal cord, and in brain areas lacking a blood-brain barrier to macromolecules.
      In addition to neuronal populations, stathmin-antibodies intensely labeled
      choroid plexuses. Many other brain regions exhibited moderate neuronal
      immunostaining. The distribution of stathmin-immunoreactive processes was in some
      areas relatively heterogeneous. Intense immunoreactivity was observed in some
      fiber tracts (corpus callosum, anterior commissure, inferior cerebellar peduncle,
      etc.) but was missing in others (internal capsule, posterior commissure, etc.).
      Some brain areas rich in immunoreactive neurons also displayed an intense
      immunoreactivity of the neuropile, whereas others contained either immunoreactive
      cells or fibers. In the human brain, stathmin immunostaining occurred in many
      areas, corresponding to those identified in the rat, with the exception of the
      cerebral cortex, the hippocampal fascia dentata, and the substantia nigra. The
      present results support our suggestion that, in addition to its involvement in
      cell proliferation and differentiation, stathmin may also be related to
      regulation of differentiated cell functions, as it appears to be a major
      signaling protein in widespread areas of the adult brain in both rat and human.

PMID- 8288777
TI  - Frontal granular cortex input to the cingulate (M3), supplementary (M2) and
      primary (M1) motor cortices in the rhesus monkey.
AB  - Although frontal lobe interconnections of the primary (area 4 or M1) and
      supplementary (area 6m or M2) motor cortices are well understood, how frontal
      granular (or prefrontal) cortex influences these and other motor cortices is not.
      Using fluorescent dyes in rhesus monkeys, we investigated the distribution of
      frontal lobe inputs to M1, M2, and the cingulate motor cortex (area 24c or M3,
      and area 23c). M1 received input from M2, lateral area 6, areas 4C and PrCO, and
      granular area 12. M2 received input from these same areas as well as M1; granular
      areas 45, 8, 9, and 46; and the lateral part of the orbitofrontal cortex. Input
      from the ventral part of lateral area 6, area PrCO, and frontal granular cortex
      targeted only the ventral portion of M1, and primarily the rostral portion of M2.
      In contrast, M3 and area 23c received input from M1, M2; lateral area 6 and area
      4C; granular areas 8, 12, 9, 46, 10, and 32; as well as orbitofrontal cortex.
      Only M3 received input from the ventral part of lateral area 6 and areas PrCO,
      45, 12vl, and the posterior part of the orbitofrontal cortex. This diversity of
      frontal lobe inputs, and the heavy component of prefrontal input to the cingulate
      motor cortex, suggests a hierarchy among the motor cortices studied. M1 receives
      the least diverse frontal lobe input, and its origin is largely from other
      agranular motor areas. M2 receives more diverse input, arising primarily from
      agranular motor and prefrontal association cortices. M3 and area 23c receive both
      diverse and widespread frontal lobe input, which includes agranular motor,
      prefrontal association, and frontal limbic cortices. These connectivity patterns
      suggest that frontal association and frontal limbic areas have direct and
      preferential access to that part of the corticospinal projection which arises
      from the cingulate motor cortex.

PMID- 8288778
TI  - Ionizing radiation therapy in dermatology.
AB  - The introduction of new surgical techniques and other therapeutic modalities has
      markedly influenced the use of ionizing radiation therapy in dermatology. X-rays
      and electron beams are now used only for a limited number of indications in
      carefully selected patients. Since surgical approaches have gained popularity in
      the treatment of skin tumors, not all dermatologists are familiar with the
      benefits of ionizing radiation for patients with cutaneous neoplasms and certain
      other skin disorders. This article reviews modern indications for radiation
      therapy in dermatology. Important physical and biologic factors, radiation side
      effects, radiation protection measures, and therapeutic results will also be
      discussed. Although the use of radiotherapy in dermatology has in large part been
      supplanted in recent years by other forms of treatment, ionizing radiation
      continues to be an essential therapeutic alternative for many cutaneous tumors
      and some skin diseases. It is important to be familiar with the principles of
      radiotherapy so that optimal therapy can be selected for individual patients.

PMID- 8288779
TI  - Oral manifestations of gold allergy.
AB  - BACKGROUND: Sensitization to gold in a large group of patients suspected of
      clinical allergy to this metal has not been reported. OBJECTIVE: Two hundred
      patients with symptoms of persistent oral mucosal or cutaneous lesions that were
      possibly related to allergy to constituents of gold alloys or gold jewelry were
      patch tested to determine the frequency of sensitization. METHODS: Patch testing
      was performed with the European standard series and a series of dental materials
      including three different salts of gold. A persistent papular reaction to gold
      (tri)chloride was considered a positive reaction. RESULTS: In 17 patients (8.5%,
      all women, mean age 50.2 years) persistent papular patch test reactions to both
      0.5% and 1.0% gold(tri)chloride were observed. In five of seven patients with
      oral lichen planus (OLP) and in one of six patients with the burning mouth
      syndrome, gold in the dentures was replaced. Particularly in patients with OLP, a
      significant but variable improvement was observed. In all cases in which gold was
      replaced and improvement occurred, the patients were sensitized to 0.5%
      gold(tri)chloride. One patient with allergic contact stomatitis and one patient
      with allergic contact dermatitis healed completely after gold had been replaced.
      CONCLUSION: Sensitization to gold should be considered as a possible cause of
      allergic contact dermatitis and allergic contact stomatitis as well as a
      pathogenic or triggering factor in OLP.

PMID- 8288780
TI  - Lymphomatoid papulosis: a clinical and histopathologic review of 53 cases with
      leukocyte immunophenotyping, DNA flow cytometry, and T-cell receptor gene
      rearrangement studies.
AB  - BACKGROUND: Lymphomatoid papulosis (LyP) is a recurrent hemorrhagic papular skin
      eruption with a clinically benign course and histopathologic features of
      lymphoma. OBJECTIVE AND METHODS: To better characterize this disease, we studied
      53 patients seen since 1965. RESULTS: A lymphoproliferative malignancy developed
      within 2 to 36 years after onset of LyP in eight patients. Histologically, the
      dermis in LyP showed an infiltrate of large (type A) or small (type B) atypical
      lymphocytes. The large atypical cells (type A) stained with CD30 (Ber-H2). Seven
      of the patients in whom lymphoma developed had type A histologic features. DNA
      flow cytometry showed mainly a diploid pattern, except for two cases that showed
      aneuploidy. Five of 11 patients showed T-cell receptor (TCR) clonal gene
      rearrangements; lymphoma has not developed in these patients. One patient had a
      TCR rearrangement in a plaque of mycosis fungoides but not in the LyP lesion.
      CONCLUSION: LyP is either a reactive skin condition or a localized lymphoid
      malignancy. Neither DNA flow cytometry nor TCR gene rearrangement can predict the
      15% to 19% of patients in whom a lymphoma will develop. Continued observation of
      all patients is essential.

PMID- 8288781
TI  - Lichen planus associated with neoplasia: a cell-mediated immune response to tumor
      antigens?
AB  - BACKGROUND: Individual case reports have suggested an occasional association of
      lichen planus with internal malignancy. OBJECTIVE: Our purpose was to describe
      five patients with a neoplastic disease in whom lichen planus developed. METHODS:
      Serologic and immunopathologic studies were conducted. RESULTS: No evidence of
      autoantibody production characteristic of paraneoplastic pemphigus was found, and
      antibodies reactive with basal cell keratinocytes were not detected. CONCLUSION:
      Lichen planus may be rarely induced by neoplasia. A cell-mediated immune reaction
      possibly causes this phenomenon.

PMID- 8288782
TI  - Acitretin in the treatment of severe lichen sclerosus et atrophicus of the vulva:
      a double-blind, placebo-controlled study.
AB  - BACKGROUND: Promising results have been reported from treatment with oral
      retinoids in patients with severe lichen sclerosus et atrophicus (LSA) of the
      vulva. OBJECTIVE: The aim of our study was to determine the efficacy of acitretin
      (20 to 30 mg/day) for 16 weeks in LSA. METHODS: Seventy-eight patients were
      enrolled into a multicenter, randomized, placebo-controlled, double-blind trial.
      The primary measure of efficacy was the "responder" rate based on the assessment
      of characteristic clinical features of LSA of the vulva (pruritus, burning,
      atrophy, hyperkeratosis, and secondary features such as erosions, ulcers, edema,
      or lichenification) and on the extent of the lesions. RESULTS: From the 46
      patients eligible for efficacy analysis, a significantly higher number of
      responders was observed in the acitretin-treatment group (14 of 22 patients) as
      compared with the placebo-treatment group (6 of 24 patients). Typical retinoid
      adverse reactions were observed in all patients receiving active drug.
      CONCLUSION: Acitretin is effective in treating women with severe LSA of the
      vulva.

PMID- 8288783
TI  - The pathogenesis and clinical significance of xanthelasma palpebrarum.
AB  - Xanthelasma palpebrarum is the most common type of xanthoma. On average, only
      half the patients with xanthelasma palpebrarum are hyperlipidemic. This review is
      an attempt to elucidate the pathogenesis and clinical significance of xanthelasma
      palpebrarum, especially its suggested role as a marker for increased risk for
      atherosclerosis. In hyperlipidemic patients with xanthelasma, the risk for
      atherosclerosis may be inferred from the associated lipoprotein and
      apolipoprotein abnormalities. The possible risk for atherosclerosis in
      normolipidemic patients with xanthelasma is more obscure because of the relative
      paucity of epidemiologic data and the conflicting results in some of the lipid
      studies. Several studies, however, showed decreased high-density lipoprotein
      cholesterol levels and other lipoprotein and apolipoprotein abnormalities that
      are associated with atherosclerosis. Therefore, on the basis of the present data,
      determining the plasma lipoprotein and apolipoprotein levels (especially those
      associated with increased risk for atherosclerosis) in each normolipidemic
      patient with xanthelasma appears to be justified.

PMID- 8288784
TI  - Malignant cutaneous tumors in children. Twenty years of experience at a large
      pediatric hospital.
AB  - The frequency of different malignant cutaneous tumors (MCTs), primary and
      metastatic, in children is not known. We reviewed all MCTs, primary and
      metastatic, seen during a 20-year period in a large general pediatric hospital.
      Fifty-three MCTs, 36 primary and 17 metastatic, were diagnosed in 36,207
      pediatric dermatology patients. The incidence was 1.4 per 1000 patients. The
      relative frequency of occurrence of the different tumors was as follows:
      rhabdomyosarcoma, 25%; lymphomas, 19%; basal cell carcinoma, 13%; leukemia, 13%;
      neuroblastoma, 10%; malignant melanoma, 6%; squamous cell carcinoma, 6%;
      unclassified sarcomas, 4%; epithelioid schwannoma, 2%; ependymoma, 2%. The mean
      follow-up was 3 years; 48% died, 27% were lost to follow-up, and 25% are under
      control. We conclude that primary and metastatic MCTs in children are rare. Their
      types differ from MCTs in an older age population. MCTs in children are
      associated with a high mortality rate, often related to late recognition.

PMID- 8288785
TI  - Polymerase chain reaction: basic concepts and clinical applications in
      dermatology.
AB  - The polymerase chain reaction (PCR) has been extensively used in basic science
      research, and the clinical potential of PCR is only now beginning to be realized.
      The PCR is based on the fundamental DNA replication process that occurs in every
      living cell. PCR is essentially an in vitro adaptation of the in vivo DNA copying
      process. Because PCR is so efficient at amplifying even picogram quantities of
      DNA, contamination with even trace amounts of nucleic acids can lead to the
      generation of unwanted DNA sequences and false-positive test results. Despite
      this, there has been rapid growth in the use of PCR in biomedical research and
      clinical diagnostics. PCR is the most sensitive test for herpes simplex virus,
      varicella-zoster virus, and human papillomavirus infections. Other diagnostic
      uses, including tests for genetic diseases, cancers, and other infectious
      diseases, are evolving.

PMID- 8288786
TI  - Febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta.

PMID- 8288787
TI  - Palmoplantar pigmentation: a clue to alkaptonuric ochronosis.

PMID- 8288788
TI  - Dermal spherulosis (myospherulosis) after topical treatment for psoriasis.

PMID- 8288789
TI  - Purpuric "gloves-and-socks" syndrome: histologic, immunofluorescence, and
      polymerase chain reaction study.

PMID- 8288790
TI  - Mycobacterium haemophilum skin disease successfully treated with excision.

PMID- 8288791
TI  - Localized keratosis follicularis associated with menotropin treatment and
      pregnancy.

PMID- 8288792
TI  - Occupationally induced allergic contact dermatitis to
      methylchloroisothiazolinone/methylisothiazolinone among machinists.

PMID- 8288793
TI  - Eruptive vellus hair cyst and steatocystoma multiplex in a patient with
      pachyonychia congenita.

PMID- 8288794
TI  - Unusual acquired dermal melanocytosis.

PMID- 8288795
TI  - Dove-associated gamasoidosis: a case of avian mite dermatitis.

PMID- 8288796
TI  - Significance of in vivo pepper-dot epidermal nuclear reactions: correlation with
      anticentromere antibodies and CREST syndrome.

PMID- 8288797
TI  - The readability of patient education materials designed for patients with
      psoriasis.

PMID- 8288798
TI  - Management of linear verrucous epidermal nevus with topical 5-fluorouracil and
      tretinoin.

PMID- 8288799
TI  - Allergic contact dermatitis mistaken for mycosis fungoides.

PMID- 8288800
TI  - Treatment of generalized bullous pemphigoid with oral tetracycline.

PMID- 8288801
TI  - Papular-purpuric "gloves and socks" syndrome caused by measles virus.

PMID- 8288803
TI  - JDR special issue, 1994 meeting abstracts. Seattle, Washington, March 10-13,
      1994.

PMID- 8288802
TI  - Granulomatous leg ulcers: an unusual presentation of Crohn's disease in a young
      man. Inflammatory Bowel Disease Study Group.

PMID- 8288804
TI  - Chemical peels. The common channel.

PMID- 8288805
TI  - Dermatologic surgery of the hand. General principles and avoiding complications.
AB  - Dermatologists and dermatologic surgeons are frequently presented with
      significant pathology of the hand. Because the hand plays such a unique and
      important role in man's everyday life, preservation and restoration of its form
      and function is critical. The hand is both powerful and extremely delicate.
      Before performing any procedures in this area, dermatologists and dermatologic
      surgeons must have a clear understanding of the cutaneous and deep anatomy of the
      hand and digits, as well as a thorough knowledge of the disease process being
      treated and the modality being used. This article reviews the intricate anatomy,
      the proper hemostasis and anesthesia, and many of the complications seen in
      dermatologic surgery and procedures of the hand, digits, and nails. With
      appropriate preoperative evaluation and precautions, many dermatologic procedures
      may be safely performed on the hand.

PMID- 8288806
TI  - Verruca vulgaris and radiation exposure are associated with squamous cell
      carcinoma of the finger.
AB  - BACKGROUND: Factors associated with the development of squamous cell carcinoma
      (SCC) of the finger are verruca vulgaris, radiation exposure, burns, and arsenic
      ingestion. OBJECTIVES: We wish to further document the relationship between human
      papillomavirus (HPV) and roentgen exposure to squamous cell carcinoma of the
      finger. METHODS: A retrospective study of 32 cases of digital squamous cell
      carcinoma seen at UCLA Medical Center was performed. RESULTS: Ten patients (31%)
      had histories of verrucae at the site of the carcinoma. Eight patients (25%) had
      histories of x-ray therapy to the hand. CONCLUSION: Our study further supports
      the association of verruca vulgaris and radiation exposure in the development of
      squamous cell carcinoma of the finger.

PMID- 8288807
TI  - Laser photocoagulation of superficial proliferating hemangiomas.
AB  - Hemangiomas present at, or soon after birth, proliferate and eventually involute.
      In spite of this, children may suffer severe psychosocial trauma during the
      formative years of their lives, and, in a proportion of cases, a cosmetically
      unacceptable result is left at the end of involution. Since flashlamp pumped dye
      lasers have been shown to selectively destroy ectatic dermal vascular tissue
      through intact epidermis, 6 patients with very early superficial cutaneous
      hemangiomas were treated. All treated areas resolved completely and treatment was
      completed by 12 months. No complications were encountered apart from mild,
      temporary post-inflammatory hyperpigmentation which was seen in one patient.
      This, however, resolved completely within 3 months of treatment. Flashlamp pumped
      dye lasers are thus able to effect complete resolution of very superficial
      proliferating cutaneous hemangiomas in neonates and infants without the risk of
      scarring.

PMID- 8288808
TI  - Copper vapor laser and microsclerotherapy of facial telangiectases. A patient
      questionnaire.
AB  - BACKGROUND: Facial telangiectasia due to photodamage is a common disfiguring
      condition in modern society. Over the past 10 years yellow light laser
      photocoagulation has become the treatment of choice. OBJECTIVE: To compare the
      effectiveness of copper vapor laser alone with combined microsclerotherapy and
      copper vapor laser in the treatment of facial telangiectases. METHODS: Two
      hundred thirty-nine consecutive patients were asked to complete a questionnaire
      evaluating the two different treatments; 180 (75%) patients responded. RESULTS:
      Both treatments were found to be effective but patients who received the combined
      treatment gave significantly higher ratings in effectiveness and overall
      satisfaction. There was also non-significant reduction in the incidence of
      adverse effects reported by patients treated by the combined method. CONCLUSION:
      Supplementary microsclerotherapy enhances the effectiveness of copper vapor laser
      photocoagulation of facial telangiectases.

PMID- 8288809
TI  - Cryosurgery of varicose veins.
AB  - BACKGROUND: It is impossible to treat all varicose veins employing the same
      method. Cryosurgery offers a new modality for the detraction of the long and
      short saphenous vein deletion. OBJECTIVE: To describe the technique, its
      indications, potential complications, and cosmetic results. METHODS: We followed
      800 patients over 6 years. The study allows evaluation of the results of and the
      best indications for this method. With a follow up of five years, we have
      analyzed: 1) the immediate complications, and 2) middle-term results. RESULTS:
      The results of cryosurgery of varicose veins were generally comparable to those
      obtained using classical surgery (stripping). CONCLUSION: Cryosurgery of varicose
      veins is a fast and safe method for selected varicose disorders, exhibiting good
      cosmetic results.

PMID- 8288810
TI  - The glycolic acid trichloroacetic acid peel.
AB  - BACKGROUND: Chemical peeling has become increasingly popular. Technique is more
      critical in medium depth peeling than with deeper peels because of variable
      penetration of the trichloroacetic acid. OBJECTIVE: This article describes a
      novel use of two caustic agents, glycolic acid and trichloroacetic acid, to
      effect a predictable approach to medium depth peeling. METHODS: Without other
      skin preparation, 70% glycolic acid was applied to the entire face and diluted
      with water after 2 minutes. Then, 35% trichloroacetic acid was applied over the
      same areas. Biopsies were done on selected patients after 24 hours and 30, 60,
      and 90 days. RESULTS: Both clinically and histologically the glycolic
      trichloroacetic acid peel resulted in medium depth injury. Improvement in
      pigmentary dyschromias and actinic damage was impressive. CONCLUSION: The GA-TCA
      peel provides a consistent approach to medium depth peeling to add to the
      armamentarium of the dermatologic surgeon.

PMID- 8288811
TI  - Micrographic surgery.

PMID- 8288812
TI  - Parents, nurses and paediatric nursing: a critical review.
AB  - The desirability of encouraging parents to live-in with their hospitalized child
      is widely accepted (Department of Health 1991). This review traces the historical
      development of parental involvement in paediatrics. The literature reviewed shows
      that parental participation and living-in has been viewed largely as
      philosophically and professionally unproblematic. These 'cardinal principles' of
      paediatric nursing have been advocated and operationalized with little or no
      attempt made to understand what living-in is like for either parents or for the
      nurses who work with them. It is proposed that research approaches in this area
      are required which are more hermeneutic and dialogic.

PMID- 8288813
TI  - An investigation into the effects of hypoglycaemia in young people aged 16-30
      years.
AB  - This study investigates the effects of hypoglycaemia on the working, social and
      personal lives of young people aged 16-30 years (mean age 23.9 years) who have
      insulin-treated diabetes mellitus. A total of 52 questionnaires were returned
      from a sample size of 70 subjects. Quantitative and qualitative analysis revealed
      that young people's lives are disrupted to varying degrees by hypoglycaemia.
      Hypoglycaemia and the complications of diabetes were found to be a source of
      concern to the subjects in the study, although 19 (36.5%) rarely carried out any
      self-monitoring. A more flexible approach to diabetic management is indicated,
      together with an agreed consensus of diabetic control between patients and
      professionals.

PMID- 8288814
TI  - 'Holism' in the discourse of nursing.
AB  - Holism is a turbid, amorphic term, of Quixotic character, the meaning of which
      alters according to the context in which it is located. Coming to grips with
      holism has been likened to trying to hold ice, because it disappears in the
      attempt. This paper assesses the variety of meanings attached to the term, and
      the extent to which the distinctive features of holism have melted away in the
      hands of nursing.

PMID- 8288815
TI  - Populations vulnerable to the ethics of caring.
AB  - This paper presents the argument that any patient population which can be
      perceived as being culpable for the pain they are in is vulnerable to the ethics
      of caring. First, both the ethics of caring and justice are reviewed, and the
      inadequacies of each, with regard to nursing, are discussed. The problems of the
      ethics of caring are demonstrated empirically and with interviews done by the
      author. Then the impacted populations are reviewed. The conclusion presents an
      emerging vision of synthesis between the moral concepts of caring and justice.

PMID- 8288816
TI  - Ethical decision-making processes used by health care providers.
AB  - This paper reports the results of a study conducted with 18 health care providers
      (HCPs) in two Toronto hospitals. The study examined and assessed how these HCPs
      make clinical-ethical decisions in the light of a theoretical model of clinical
      ethical decision making. Nine nurses and nine doctors were interviewed through
      two-phased, in-depth, semi-structured interviews. The results suggest that, in
      relation to the two major elements of the model, namely the ethical component and
      the decision theory component, the HCPs did not follow a consistent and
      systematic pattern of ethical decision making. Differences emerged between their
      actual self-reported behaviour and their potential more capability (i.e. their
      abstract thought process). The general picture that emerged was that decisions
      were made in a narrow, habitual manner, through the elimination of the most
      significant and demanding elements of the process. HCPs' ethical approaches
      affected the entire process of the decision making: their perception of the
      problem, their search for and selection of information and evidence, and their
      development of alternatives and resultant consequences. It is suggested to (a)
      further investigate and understand the subjective realities of the individuals
      involved in the decision making processes, their values and the meaning they
      ascribe to their choices, and (b) to establish extensive educational programmes
      to enhance HCPs' decision-making capacity and subsequently promote an effective
      and responsible professional practice.

PMID- 8288817
TI  - Nurses' perceptions of patients' feelings about breast surgery.
AB  - This qualitative study was designed to gain insight into nurses' perceptions of
      patients' feelings and needs with specific reference to breast surgery. A
      grounded theory approach was adopted, based on in-depth, unstructured interviews
      with eight trained nurses working on surgical wards in a district general
      hospital. It emerged that the informants believed breast surgery patients to be
      very vulnerable and to be suffering from extreme stress and trauma. Patients were
      thought to lack knowledge regarding their treatment and condition. The nurses
      thought it to be their moral and professional duty to act as advocates for the
      patient and the family. Imposed restrictions on their advocacy role were found to
      cause a sense of frustration and powerlessness which appeared to be compounded by
      the nurses' perceived lack of counselling skills and the absence of a readily
      available counsellor or specialist nurse. Recommendations for improvements in the
      care of patients undergoing breast surgery are based upon these findings.

PMID- 8288818
TI  - Patient-controlled analgesia: a new method for old.
AB  - Patient-controlled analgesia (PCA) has successfully made the transition from a
      research tool for the investigation of pain, to a wider clinical utility as
      method of pain control. Reliable and sophisticated PCA systems have been
      commercially available for some time. The technique has been most commonly used
      for control of postoperative pain, but has also been successfully used during
      labour, after burns, in acute painful medical conditions and in terminal care. It
      is generally more effective than the traditional methods of postoperative pain
      control but not automatically so. The choice of opioid, the settings chosen for
      demand dose and the lockout interval will greatly influence the effectiveness of
      this method of analgesia. Psychological variables are also important in
      predicting the efficacy of PCA.

PMID- 8288819
TI  - Activity nursing and the changes in the quality of life of elderly patients: a
      semi-quantitative study.
AB  - In recent years increasing awareness and interest in different approaches to
      caring for elderly people have produced improvements in their psychological and
      social care. This paper evaluates the change in the quality of life which was
      brought about by the introduction of activity nursing into a continuing care
      unit. Significant changes were observed in cognitive functioning and quality of
      life. The benefits to both relatives and staff were also considerable.

PMID- 8288820
TI  - Retrospective document survey: identification, assessment and management of
      urinary incontinence in medical and care of the elderly wards.
AB  - Urinary incontinence is a common problem experienced by patients in hospital. As
      part of a series of studies, a retrospective survey was carried out of 229
      nursing and medical records of patients identified as incontinent of urine by the
      nurses-in-charge, in 14 acute medical wards and 26 health care of the elderly
      wards. The aims of the survey were to investigate the extent to which urinary
      incontinence had been identified as a problem, and to examine the nature of its
      assessment and management. The recording of the problem was found to be
      inconsistent and there was a paucity of information which might have contributed
      towards its assessment. The causes of incontinence were rarely recorded and in
      approximately half of the nursing and medical records examined there was a
      complete absence of any information related to a management plan. Where recorded,
      interventions reflected predominantly palliative measures such as routine
      toileting regimens and the use of continence aids. The implications of these
      findings are discussed.

PMID- 8288821
TI  - Relationships between demented elderly people and their families: a follow-up
      study of caregivers who had previously reported abuse when caring for their
      spouses and parents.
AB  - The aim of the study was to elucidate how relationships develop over time in
      abusive families. Family members of demented elderly people who previously
      reported abuse in the care of the elderly relatives are interviewed in a follow
      up study. In this current study the families did not mention any abusive
      behaviour. They narrated their feelings toward their care recipient in the
      following main categories: mothering, grieving, feeling guilty, distancing and
      objectifying. When the family members expressed mothering thoughts, there were no
      expressions of guilt, objectifying or distancing, and the prior relationship was
      narrated as good. The families who talked about the demented person at a distance
      or by objectifying did not express feelings of mothering or grief for the
      relative.

PMID- 8288822
TI  - Does the use of an assessment tool in the accident and emergency department
      improve the quality of care?
AB  - The aim of this study was to evaluate the effect of introducing a nursing record,
      using the SOAPE model, in the accident and emergency department. A working group
      was formed to design and implement a new record and evaluate its effect. A 6
      month teaching programme was run to prepare staff. Quality of documentation was
      measured using the Phaneuf Audit Tool both before and after the implementation of
      the new record and the teaching sessions. The results were compared. It was
      concluded that, overall, the documentation showed significant improvement.
      Therefore, it could be assumed that there had been an improvement in the quality
      of care.

PMID- 8288823
TI  - Towards clarification of convergent concepts: sense of coherence, will to
      meaning, locus of control, learned helplessness and hardiness.
AB  - The multidisciplinary field of stress and stress-related health outcomes has
      generated theoretical and practical knowledge which is of interest to nurses.
      Theoretical developments which have assumed a prominent role in the study of
      stress, health and coping include the identification of various 'stress buffers'
      several of which bear a strong conceptual resemblance to one another. Antonovsky
      has developed a Salutogenic Model of stress and resistance, which is presented in
      this paper. The model's central concept, the sense of coherence, is described and
      analysed. The sense of coherence, with its three components (meaningfulness,
      comprehensibility and manageability), is then compared and contrasted with
      similar concepts. The convergent theoretical notions which are distinguished from
      Antonovsky's coherence are: will to meaning, locus of control, learned
      helplessness and hardiness. It is hoped that this analysis will provide greater
      conceptual clarity for nurses who study and use these concepts in education,
      practice or research.

PMID- 8288824
TI  - The psychosocial needs of people with HIV and AIDS: a view from nurse educators
      and counsellors.
AB  - AIDS is an increasingly urgent issue for clinical nurses, managers and for nurse
      educators. This paper describes the analysis of part of a set of interviews with
      a purposive sample of 21 AIDS counsellors, nurse educators and other health care
      workers. In particular, response to the question: 'What are the psychosocial
      needs of the person diagnosed as HIV-positive or who has AIDS?' are discussed.
      The paper begins with a brief description of the study and then offers a more
      detailed description of the method of analysis used to obtain the findings. These
      are then reported within 16 categories. Psychosocial problems identified included
      issues of emotion, acceptance, a variety of fears, stigma, issues relating to
      insurance and travel, health care facilities and the attitudes of the Church.

PMID- 8288825
TI  - An analysis of the concept of grief.
AB  - Grief is a universal response affecting every age and culture. However, this
      concept is surrounded by ambiguity. It is poorly understood by nurses who
      encounter grieving persons with increasing frequency, especially as the
      population ages. The ability of nurses to gain an increased understanding of
      grief depends on the clarification of this concept. A concept analysis is
      described. Antecedents, attributes, referents and intervening variables of grief
      are identified. In addition, model, borderline, related, invented and contrary
      cases are described. This analysis results in a comprehensive definition of grief
      which is proposed. This definition can contribute to the foundation essential to
      guide nursing practice with grieving persons.

PMID- 8288826
TI  - Good relations: the use of a relational database for large-scale data analysis.
AB  - This paper reports our experience of analysing what may well be one of the
      largest datasets gathered on nursing practice in the United Kingdom. The study
      produced both quantitative and qualitative data and a method had to be devised
      both for analysing each form of data and for relating the two. An inexpensive
      relational database was chosen for the purpose, and experience of using it is
      reported. Detailed examples are given. We look at the strengths and weaknesses of
      such a tool, and in general it received a positive evaluation. For many nursing
      research projects, it offers some advantages over a conventional statistical
      package, especially in the following areas: offering ease of use, and hence
      control of the data, by the domain (nursing) specialist; facilitating the
      analysis of free-text data; allowing the linking of free-text and structured
      questionnaire data; permitting the testing of conjectures which arise during
      analysis; handling varying amounts of data per case; providing non-redundant
      storage of data; permitting the association of machine-readable codes and human
      readable labels; and encouraging an exploratory rather than merely analytical
      approach.

PMID- 8288827
TI  - Issues for consideration when choosing a qualitative data management system.
AB  - A primary issue in conducting qualitative research is the time required for data
      analysis. Qualitative research can be costly, since data analysis is generally
      labour intensive and our time factors into money. There is, unfortunately, no
      magic formula for hastening the conceptual tasks associated with qualitative
      analysis, yet effective qualitative data management systems (QDMS) expedite the
      mechanical tasks, those tasks associated with storing and retrieving qualitative
      data. Rapid and smooth data management increases the time one can allot to data
      analysis. Although computer QDMS are increasingly recommended for their time
      saving potential in relation to data management, some significant issues
      associated with the adoption of a computer versus a manual QDMS have not yet been
      fully explored. The purpose of this paper is to present major issues researchers
      should consider in choosing a computer or a manual QDMS. These issues include
      availability and accessibility, comfort, appropriateness, efficiency,
      thoroughness and contextualization.

PMID- 8288828
TI  - Accreditation of prior learning: andragogy in action or a 'cut price' approach to
      education?
AB  - The rapid changes in nurse education are proceeding within the wider context of
      developments in adjacent educational fields, which are themselves subject to
      external influences, and one such development is the accreditation of prior
      experiential learning (APEL). In order to be critically aware of the potential
      involved in embracing this concept, it is necessary to clarify and examine the
      influencing factors which guide the current andragogical climate of nurse
      education, and those which predispose to the recognition of APEL. Utilizing a
      case-study approach, this paper will examine the relevant issues as they relate
      to experienced students pursuing the learning outcomes of Project 2000, and will
      address the question of value for all parties concerned.

PMID- 8288829
TI  - A trainer's perspective of an innovative programme teaching health visitors about
      the detection, treatment and prevention of postnatal depression.
AB  - Health visitors in North Staffordshire, Edinburgh and Lewisham were given the
      opportunity to participate in a training programme in the detection, treatment
      and prevention of postnatal depression, based on previously reported successful
      intervention strategies. They were trained in the use of the Edinburgh Postnatal
      Depression Scale (EPDS), and given information about the value and practice of
      non-directive counselling and about preventative strategies. Knowledge
      acquisition was evaluation by self-report questionnaires given before and after
      training. The health visitors were encouraged to screen postnatal women at three
      specified times using the EPDS and to offer non-directive counselling to women
      who obtained high scores. A baseline measure of the incidence of postnatal
      depression was obtained by asking health visitors to give an EPDS form to all
      women in their caseload with a 6-month-old baby before training commenced. A
      comparison of the number of women with high EPDS scores at 6 months postnatally,
      before and after training, showed that participation in the programme enabled
      health visitors to positively influence the emotional well-being of postnatal
      women. These results have implications for the role of health visitors which is
      currently being challenged, as well as for components of their training and
      continuing professional development.

PMID- 8288830
TI  - Nurse manpower demand: a review of United Kingdom methodologies.
AB  - Forecasting the demand for nurses is a complex and difficult problem. However, in
      a climate of economic cutbacks and disadvantageous demographic trends, it is
      essential that adequate methods are developed to predict both the supply and
      demand for nurse manpower. To this end a number of methods have been constructed,
      particularly in the last decade. In this paper we survey the work that has been
      done to provide an effective way of forecasting nurse manpower demand. The two
      most common approaches are from the 'top-down' or 'bottom-up'. However, an
      evolutionary method which allows for modification and detailed refinement is more
      likely to provide a means of taking into account the complexities of the system.
      Finally, we focus on the nursing hours per patient (NHPP) ratio as a possible
      tool for demand forecasting. This index is easily calculated and is readily
      adaptable to the bottom-up approach.

PMID- 8288831
TI  - A follow-up study of the Bachelor of Nursing graduates 1982-90, University of
      Glasgow, Scotland.
AB  - In 1992 a follow-up study of the 214 graduates of the Bachelor of Nursing degree,
      University of Glasgow, was conducted. There was an adjusted response rate of
      67.05%. Overall, this study provides continuing support for the findings from
      earlier surveys which demonstrated that graduate nurses continue to work in the
      clinical field, that undergraduate nursing does not necessarily provide career
      acceleration, and that midwifery is the most sought-after additional
      qualification. More of Glasgow's graduate nurses are to be found working in high
      dependency units than would appear to be the case from other surveys on degree
      nursing courses. Glasgow's graduate nurses hold an ethos which values university
      education and life.

PMID- 8288832
TI  - Use of the mental health on-call system on a university campus.
AB  - Over the course of 1 calendar year, clinicians at a university mental health
      service collected data on every clinical case in which students presented after
      normal business hours or on weekends for urgent mental health consultation.
      During the year, 50 such incidents were recorded, which translated to a rate of
      6.6 on-call events per year per 1,000 students. Students were primarily self
      referred or referred by the student health center or residence life staff.
      Suicidal concerns, panic/anxiety, and depressive states were the three most
      common presenting complaints. Average clinician time per case was 1 1/2 hours,
      with sexual assault cases taking the most time per case, followed by substance
      abuse and suicidality. Follow-up outpatient counseling was employed in 76% of the
      cases. The results highlight the importance of on-call mental health services on
      college campuses.

PMID- 8288833
TI  - Sexually transmitted diseases in college men: a preliminary clinical
      investigation.
AB  - Continuing efforts to educate college students about the dangers of unprotected
      sexual intercourse have resulted in little evidence of positive change in sexual
      behavior. This clinical study examined the sexual behavior, perceived risk of
      human immunodeficiency virus, and pathology of 66 university men attending a
      health center's men's clinic for treatment of sexually transmitted disease (STD).
      The study demonstrated the existence of a high-risk group of men who, despite
      sexually transmitted disease pathology, high numbers of sexual partners,
      inconsistent condom use, and delays in seeking treatment, perceive their risk of
      contracting HIV/AIDS as being extremely low. This preliminary investigation
      suggests the need for specific education interventions and future in-depth
      studies of this population.

PMID- 8288834
TI  - Seasonality of Chlamydia trachomatis genital infections in university women.
AB  - Previous studies have shown seasonal fluctuations in the incidence of most
      sexually transmitted diseases, with a peak in the third quarter, but none have
      specifically evaluated Chlamydia trachomatis genital infections. From 1989 to
      1991, 8,234 women presenting to the student health centers of Florida's two
      largest universities for routine gynecologic care and diagnosis of sexually
      transmitted diseases were tested for Chlamydia trachomatis genital infections.
      The bimonthly variation in incidence was statistically significant, with a
      significant peak in the months of August and September of 10.70%, compared with
      the yearly average of 8.74%. Because the pattern of incidence of chlamydia in
      university women is seasonal, those concerned with healthcare should increase
      their efforts during the third quarter to identify infected individuals and to
      provide preventive programs.

PMID- 8288835
TI  - Students' knowledge and behavior concerning safer sex: a UK study.
AB  - Most students in institutions of further and higher education in the northeast of
      England who responded to a 1989 survey dealing with sexual behavior and safer sex
      were heterosexual and had been sexually active or intended to have sexual
      intercourse. Many students, however, believed that safer sex implied having no
      sex at all or were unaware of the role of nonpenetrative sex in preventing human
      immunodeficiency virus (HIV) infection. They did not use condoms, in spite of
      having positive attitudes about condom use, and they engaged in one or more
      sexual activities that increased the risk of acquiring HIV infection. In view of
      the increasing incidence of acquired immunodeficiency syndrome (AIDS), the
      authors assert, these findings are cause for concern and require concerted action
      by health educators and society to encourage safer sex practices and to prevent
      the spread of HIV infection.

PMID- 8288836
TI  - Nursing's central role in healthcare.

PMID- 8288837
TI  - Protocols for college health nurses: alive and well in the 1990s.
AB  - This article seeks to assist college health nurses in developing appropriate
      protocols for patient care. In addition, the authors outline factors influencing
      protocol content, design, and development and describe steps in creating
      individualized protocols by practice setting. To provide college health nurses
      with a basic understanding of protocols, the authors offer definitions and
      examples of appropriate and inappropriate use, and show how protocols can
      influence the delivery of patient care. Although protocols may provide college
      health nurses with directives for managing specific health problems, they require
      a sophisticated level of judgment and skill in their implementation.

PMID- 8288838
TI  - The condom race.
AB  - The condom race is a hands-on activity that can help teach young people condom
      use as part of safer sex practices. Although it is well documented that students
      know about condom use, they often do not do what they know they should. One
      possible explanation for this is that the students may lack the skills and
      confidence they need to have when they use condoms. The condom race offers
      students a chance to gain skills and confidence in a humorous, nonthreatening
      way. During the exercise, which is based on the concept of a relay race, students
      touch, feel, and practice putting condoms on penis models. After participating in
      the activity, students reported increased confidence in their ability to use,
      discuss, and carry condoms. The condom race is a quick, amusing, and easy
      activity.

PMID- 8288839
TI  - Prematriculation immunization requirements of American colleges and universities.
AB  - The authors surveyed a stratified sample of 880 colleges and universities in the
      United States to assess the status and characteristics of their prematriculation
      immunization requirements (PIRs). On the basis of a 90% return (796 responses),
      they estimated that 55% of US colleges and universities had implemented a PIR at
      the time of the survey. Among schools with PIRs, measles vaccine was almost
      universally required, with 74% requiring two doses, mumps vaccine was required by
      70%, and rubella vaccine by 92%. Hepatitis B vaccine was rarely required and was
      usually recommended only for students in health-profession programs. The
      strongest determinant of having a PIR was the presence of a state law or regents'
      policy. PIRs implemented under the aegis of a state law were, on average, less
      comprehensive but better enforced. Other factors associated with the
      implementation of a PIR included membership in the American College Health
      Association (ACHA), the presence of a student health clinic, and availability of
      record-keeping personnel.

PMID- 8288840
TI  - Research in college health. 4: Analyzing and communicating results.
AB  - The final article in this series on research in college health deals with the
      analysis and communication of research data. The authors introduce descriptive
      and inferential statistics and summarize the applicability of different types of
      statistical analysis to college health research. Two major means of conveying
      results, conference presentations and journal articles, are also described and
      some guidelines for the effective communication of findings are offered.

PMID- 8288841
TI  - Inhibitory effect of gomisi on reductive metabolism of halothane.
AB  - The effect of Gomisi (dried ripe fruit of schizandra chinensis) on
      chlorodifluoroethylene (CDE) and chlorotrifluoroethane (CTE) formation was
      investigated. The incubation mixtures for the measurement of reductive
      metabolites of halothane consisted of liver microsomal suspensions, 3 mM NADPH,
      extract solution of Gomisi and halothane in 0.1 M potassium phosphate buffer (pH
      7.4). The production of CDE and CTE was inhibited by Gomisi in a dose-dependent
      way. The production were reduced to half in the presence of 0.5% Gomisi extract
      in the reaction mixture. The results suggest that Gomisi can inhibit the
      reductive metabolism of halothane in vitro; thus it may protect against halothane
      induced hepatitis.

PMID- 8288842
TI  - High-performance liquid chromatography detection of sulfide in tissues from
      sulfide-treated mice.
AB  - The biological and forensic use of ion-interaction reversed-phase high
      performance liquid chromatography for the determination of hydrogen sulfide
      derived methylene blue is evaluated by measuring the sulfide content in tissues
      from sulfide-treated mice. Various preparative conditions were examined. The
      determinations of background levels of sulfide from brain, liver and kidney were
      compared to sulfide levels from mice exposed to 60 micrograms g-1 sodium
      hydrosulfide. At the time of death, significant increases above background
      sulfide levels were measured for all three biological tissues. To evaluate its
      forensic potential, we used this sulfide detection methodology to evaluate
      comparatively the sulfide levels from fresh and frozen samples of brain, liver
      and kidney. The stability of sulfide levels obtained from frozen brain makes this
      tissue the most reliable tissue for forensic evaluation. Samples of brain, liver
      and kidney obtained within 24 h of death by sulfide intoxication had demonstrable
      elevations in sulfide concentration.

PMID- 8288843
TI  - Risk assessment and management of chemical contaminants in fishery products
      consumed in the USA.
AB  - In the USA a small proportion of fishery products are contaminated with
      appreciable amounts of potentially hazardous contaminants. However, risks to
      consumers are not generally high. Inorganic contaminants with the greatest
      potential for toxicity are antimony, arsenic, cadmium, lead, mercury, selenium
      and sulfites. Among organic compounds, polychlorinated biphenyls, dioxins,
      several chlorinated hydrocarbon insecticides, certain processing-related and
      aquaculture-related contaminants pose potential risks for consumers. Log-normal
      distributions appear to provide good descriptions of the pattern of variation of
      contaminant concentrations among different geographic areas, and some
      contaminants (mostly organic) appear to be much more variable than others. This
      variability offers a solution for reduction of exposure through restricting the
      harvest of aquatic organisms from specific sites, and by excluding certain
      species. It is recommended that: (i) existing State and Federal regulations and
      environmental monitoring be strengthened and enforced to minimize contamination
      of the aquatic environment; (ii) a program of shared responsibility be
      instituted, where Federal agencies develop a set of monitoring and inspection
      practices and state agencies assume responsibility for primary control, site
      closures and advisories issue; (iii) research and public education by government
      agencies and health professionals be expanded to determine actual risks and
      approaches to manage them; (iv) mandatory labeling be considered for specific
      contaminants; (v) a better system requiring international agreements be developed
      in order to minimize the differences among various national regulatory
      approaches.

PMID- 8288844
TI  - Modulation of hepatic glutathione system of enzymes in suckling mouse pups
      exposed translactationally to malathion.
AB  - The present study examines the transmammary modulation of the glutathione system
      of enzymes in the F1 generation of mouse pups postnatally exposed to malathion.
      Lactating Swiss albino mice received either 30 or 100 mg malathion kg-1 body wt.
      (98% pure) for 14 or 21 days postpartum. The acid-soluble sulphydryl content was
      significantly increased (P < 0.001) in the liver of 14-day-old pups of dams that
      had received the higher malathion dose. A similar significant increase was seen
      in the 21-day-old male pups of dams that had received 30 mg (P < 0.05) or 100 mg
      (P < 0.01) malathion kg-1 body wt. Dams showed an enhanced hepatic glutathione S
      transferase activity following treatment with 100 mg malathion kg-1 body wt. for
      14 days (P < 0.02) and 21 days (P < 0.001). Pups of either age groups also showed
      enhanced hepatic glutathione S-transferase activity (P < 0.001). A significant
      enhancement in glutathione reductase activity was observed with malathion
      treatment in livers of dams and pups (P < 0.001). However, dams that had received
      30 mg malathion kg-1 body wt. daily for 21 days or 100 mg malathion kg-1 body wt.
      for either 14 or 21 days showed significantly reduced hepatic glutathione
      peroxidase activity (P < 0.01, P < 0.001). A significant decrease in glutathione
      peroxidase activity was also observed in the liver of the 21-day-old male (P <
      0.01) and female (P < 0.02) pups of dams that were treated with the higher dose
      of malathion.

PMID- 8288845
TI  - Urinary thiodiglycolic acid and thioether excretion in male rats dosed with 1,2
      dichloroethane.
AB  - 1,2-dichloroethane (DCE) is extensively metabolized and partially excreted in
      urine as thioether compounds, which include thiodiglycolic acid (TDGA). In this
      study, we have compared the urinary excretion of TDGA and thioethers in the rat
      after administration of increasing doses of DCE. Male Sprague Dawley rats were
      given a single oral dose of labelled [14C]DCE (0.125 to 8.08 mmol kg-1 body wt.)
      and 24-h urine samples were collected. The TDGA and thioethers were determined in
      urine by a gas chromatography method and by the thioether assay after alkaline
      hydrolysis, respectively. The percentage of the administered radioactivity that
      was excreted in urine decreased with increasing dose of DCE and ranged between 63
      and 7.4%. The amount of TDGA increased proportionally to the DCE dose up to 1.01
      mmol DCE kg-1 body wt. and corresponded to 0.22 mmol TDGA mmol-1 DCE. Up to 0.25
      mmol DCE kg-1 body wt., the amount of thioethers recovered in urine was not
      significantly different as compared to the vehicle control group (11.8 +/- 0.6
      mumol SH equiv. kg-1 body wt., n = 10). From the 0.25-4.04 mmol DCE kg-1 body wt.
      dose, the amount of thioethers increased linearly with the dose of DCE and
      corresponded to 0.028 mmol SH equiv. mmol-1 DCE. The ratio between urinary
      thioethers and TDGA increased with the DCE dose and reached 0.17 +/- 0.01 (n = 5)
      at a dose of 8.08 mmol DCE kg-1 body wt. Moreover, TDGA contents determined in
      urine by gas chromatography before and after alkaline hydrolysis were not
      significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288846
TI  - Differential sensitivity of DBA/2 and C57BL/6 mice to cyclophosphamide.
AB  - Early and delayed toxicity of a single dose of 300 mg kg-1 cyclophosphamide (CP)
      was investigated in male DBA/2 and C57BL/6 mice. Early toxicity (up to 30 days
      after CP administration) resulted in 36.6% lethality in DBA/2 and no mortality in
      C57BL/6 mice. Delayed toxicity (after 30 days) occurred primarily in DBA/2 mice,
      resulting in a survival of 3% in DBA/2 and 93% in C57BL/6 mice on day 125 after
      CP administration. Early modifications brought about by CP in erythrocytes and
      leucocytes, and spleen and liver indexes (mg organ g-1 body wt.) were rather
      similar in DBA/2 and C57BL/6 strains. However, CP treatment caused a profound
      cell depletion in DBA/2 bone marrow owing, in part, to the fact that the number
      of cells in bone marrow of normal DBA/2 mice was much lower than that in normal
      C57BL/6 mice. Furthermore, the thymus index (mg organ g-1 body wt.) decreased
      sooner in DBA/2 than in C57BL/6 animals and no sign of recovery was evident in
      the former even after 10 days, whereas recovery in the latter started on day 5
      after injection. Differential sensitivity of DBA/2 and C57BL/6 strains to CP
      could be due to differences in activation and/or inactivation of the drug, or to
      the increased effect of CP on DBA/2 bone marrow resulting in damage to pre-T
      cells that normally participate in thymus recovery.

PMID- 8288848
TI  - Hexamethylene diisocyanate.

PMID- 8288847
TI  - Predicted toxicities of aryl alkanols and related compounds.
AB  - The relative toxicity of selected aryl and/or alkyl alcohols was evaluated in the
      batch culture Tetrahymena pyriformis population-growth impairment assay.
      Chemicals evaluated included normal and branched primary alcohols with mono-, bi-
      or diaromatic substituents as well as aryl-substituted ethers. Log 1
      octanol/water partition coefficients (log Kow) along with previously developed
      quantitative structure-activity relationships (QSARs) for both the non-polar
      narcosis and polar narcosis mechanism of action were used to predict relative
      toxicity. Observed and predicted toxicities measured as log IGC50(-1) were
      compared. All phenols and naphthyl-substituted compounds, as well as the biphenyl
      methanols, benzhydrols and 1,1-diphenylethanol, model more accurately as polar
      narcotics. Both monoaromatic- and diaromatic-substituted branched arylalkyl
      alcohols, as well as monoaromatic ethers, model best as non-polar narcotics. The
      C1-C6 straight-chain aryl alkanols, as well as 3-phenyl-1-butanol, model
      intermediately between non-polar and polar narcosis. The triaromatic-substituted
      alcohol was not toxic at saturation. These findings are consistent with the idea
      that narcosis, the reversible state of arrested bioactivity, is a series of
      mechanisms.

PMID- 8288849
TI  - Toluene.

PMID- 8288850
TI  - The antibody response in serum, intestinal wall and intestinal lumen of NMRI mice
      infected with Echinostoma caproni.
AB  - Groups of mice (NMRI) were infected with 0, 6 and 25 metacercariae of the
      intestinal trematode Echinostoma caproni. An enzyme linked immunosorbent assay
      (ELISA) was developed for measuring the specific IgM, IgG and IgA antibody
      responses in serum, small intestinal tissue and small intestinal lumen of the
      mice, by using a crude adult E. caproni antigen. In infected mice, significant
      levels of IgM were measured in the sera from day 14 after infection and of IgG
      and IgA from day 28 after infection. Early in the infection, the mean level of
      serum IgM was higher in 6-worm infections than in 25-worm infections. Late in the
      infection, higher mean levels of IgA were reached in the serum of mice with high
      than in those with low dose infections. The onset of appearance of antibodies in
      the tissue of the small intestine reflected the picture seen in the serum. For
      IgM, and to a lesser degree for IgG, the highest mean antibody levels appeared in
      the posterior sections of the small intestinal wall, where also the parasites
      were located. The mean level of IgA, however, was uniform throughout the length
      of the small intestinal tissue. High levels of specific IgA were detected in the
      lumen of the small intestine on day 28 after infection, especially in the
      anterior sections, where only few parasites were located. No specific IgM or IgG
      could be detected in the intestinal lumen on this day. The results are related to
      the intestinal location and the pattern of expulsion of E. caproni in the mouse
      host.

PMID- 8288851
TI  - Comparative spectral, electrophoretic and isoelectric properties of trematode
      haemoglobins.
AB  - A comparative study of the spectral, electrophoretic and isoelectric properties
      of the haemoglobins of three trematodes, Paramphistomum epiclitum, Gigantocotyle
      explanatum and Gastrothylax crumenifer was carried out. A high absorption in the
      beta band region indicates that trematode haemoglobins have high oxygen
      affinities. Electrophoretic mobilities of all trematode and their host
      haemoglobins were different. The isoelectric points of trematode haemoglobins
      were found to focus in the acidic range except that of G. crumenifer haemoglobin
      I, which focused at an alkaline pH.

PMID- 8288852
TI  - Embryogenesis in Litomosoides carinii from pyridoxine deficient cotton rats.
AB  - Pyridoxine (vitamin B6) deficiency was induced in cotton rats which were then
      infected with the filarial parasite Litomosoides carinii. Embryogenesis was
      assessed microscopically in worms taken from pyridoxine deficient cotton rats and
      from various categories of control animals. Embryogenesis was retarded in worms
      from pyridoxine deficient hosts and more abnormal embryos were present in such
      worms than in those from control animals.

PMID- 8288853
TI  - Water sources and other determinants of dracunculiasis in the northern region of
      Ghana.
AB  - This paper describes a study carried out in a rural area of Ghana on the drinking
      water sources and other determinants of dracunculiasis (guinea worm disease). The
      results confirm the association between water source choice and the prevalence of
      the disease. A logistic regression model was used to show the combined effect of
      several behavioural, biological, and environmental risk factors. The important
      behavioural factors were related to the head of household, fetching of water,
      travelling, and farming. Age was found to be an important biological risk factor
      for dracunculiasis, but the greatest relative risk applied to those who had
      suffered from guinea worm disease in the previous year. Although males were
      significantly more infected than females when analysing the raw data, sex did not
      prove to be a significant risk factor in this model. Village of residence was an
      important environmental risk factor for dracunculiasis. Factors related to socio
      economic status were not associated with the risk of infection. The paper
      concludes by presenting the policy implications of the study findings.

PMID- 8288854
TI  - Isoenzymatic pattern of glucose 6-phosphate dehydrogenase from Ascaris suum.
AB  - The isoenzymatic pattern of glucose 6-phosphate dehydrogenase (abbreviation G6PD)
      from Ascaris suum has been studied by vertical polyacrylamide gel (PAGE) and
      horizontal starch gel electrophoresis. After polyacrylamide gel electrophoresis,
      two stained zones could be identified. One corresponded to tetrazolium oxidase
      activity; since this zone was stained even in the absence of glucose 6-phosphate
      (G6P), non-specific staining could be detected. In the other zone of activity,
      seven regularly-spaced bands were identified by staining in the presence of G6P
      and NADP as substrates. By using starch gel electrophoresis, different
      electrophoretic patterns for G6PD have been observed in the muscular sac,
      intestine and reproductive system from A. suum. The existence of three different
      alleles of G6PD in the same individual suggests the existence of at least two
      genes for this enzyme.

PMID- 8288855
TI  - Cryopreservation of Angiostrongylus cantonensis third-stage larvae.
AB  - An optimum protocol for the cryopreservation of third-stage larvae (L3) of
      Angiostrongylus cantonensis was determined by: (i) use of different dimethyl
      sulphoxide (DMSO) concentrations; (ii) use of different FBS concentrations in
      RPMI-1640 medium; and (iii) variation in the thawing temperature. Studies showed
      that with concentrations of DMSO at 4.8% and FBS at 40% and a thawing temperature
      of 43 degrees C, L3 survival assessed by motility was highest at 56%. The
      infectivity of the cryopreserved L3 of A. cantonensis was 20% compared to
      controls obtained from slugs.

PMID- 8288856
TI  - Effect of irradiation on the viability of Angiostrongylus cantonensis and A.
      costaricensis infective larvae.
AB  - Infective larvae (third-stage larvae) of both Angiostrongylus cantonensis and A.
      costaricensis from their snail intermediate host were subjected to either X-ray
      or gamma-ray irradiation. The viability of the irradiated larvae was assayed by
      oral inoculation of the larvae into rodents (A. cantonensis in mice and rats, A.
      costaricensis in mice only). From the results of worm recovery, the minimal dose
      of irradiation that inhibited the infectivity of the third-stage larvae of A.
      cantonensis and A. costaricensis was 2 and 4 kGy, respectively.

PMID- 8288857
TI  - The effect of levamisole on acetylcholinesterase secretion by male and female
      Heligmosomoides polygyrus during ageing.
AB  - The inhibition of acetylcholinesterase secretion by male and female
      Heligmosomoides polygyrus was tested on worms taken from experimentally infected
      mice and maintained for 3 days in vitro in levamisole. The dose inhibiting 50% of
      enzyme secretion (ID 50) of male worms was twice the ID 50 for female worms. A
      similar difference was observed in vivo between the dose of levamisole removing
      50% (LD50) of male and female worms from the mouse. Acetylcholinesterase
      secretion by worms and ID 50 were tested in vitro at 3-weekly intervals from 3 to
      21 weeks post infection (WPI). Acetylcholinesterase secretion was always
      significantly higher for male than for female worms. A decrease of ID 50,
      correlated with the age of the worms was observed: from 1.5 to 0.5 micrograms/ml
      for males and from 0.7 to 0.1 micrograms/ml for females. These results were
      confirmed in vivo by a higher efficacy of the anthelminthic at 21 than at 4 WPI.

PMID- 8288858
TI  - Some observations on hydatidosis in Jordan.
AB  - A total of 2.8% (5 of 176) sera from schoolchildren and university students were
      seropositive for hydatidosis (Echinococcus granulosus), by the ELISA IgE test.
      The prevalence of seropositivity was 4.5% among females of all age groups (5-24
      years) and among males of the age group 18-24 years. Males of the age group (5-17
      years) were seronegative. The ratio of seropositivity between schoolboys and
      schoolgirls was 1:4. Sera collected from 1085 university students, aged 18-24
      years, and from 1656 outpatients from northern and central Jordan, and the Jordan
      River valley, when tested by the IHA test, revealed the presence of anti-hydatid
      agglutinating antibodies in 5.16% (56 of 1085) and in 3.6% (60 of 1656)
      respectively, with a male to female infection ratio of 1:3 in the university
      students and 1:1.1 in the outpatients. Intensity, prevalence and cyst fertility
      of E. granulosus increased in sheep with age. The results of this study indicate
      that hydatidosis is in an endemic steady state in Jordan with estimated economic
      losses of JD 3.0 (= US $4.4) per infected sheep.

PMID- 8288859
TI  - Three-dimensional co-localization of nucleolar argyrophilic components and DNA in
      cell nuclei by confocal microscopy.
AB  - Silver dots deposited specifically on proteins of the nucleolar organizer regions
      (Ag-NOR proteins) after a one-step silver staining technique were visualized in
      cells in culture, in cells in smears, and in tissue sections, with a scanning
      laser confocal microscope working in the reflectance mode. After specific
      labeling of DNA with the fluorescent dye chromomycin A3, DNA and silver dots
      could be observed either individually or simultaneously. Therefore, it was
      possible to study the three-dimensional organization of nucleolar silver-stained
      structures relative to DNA with a high X, Y, and Z resolution. Our results showed
      that the argyrophilic components are organized as a twisted necklace structure
      within interphase nucleoli of cells in culture. We also demonstrated a striking
      three-dimensional symmetric disposition of NORs within the two sets of
      chromosomes in telophase cells. Similar results were obtained for cells in
      smears, although their three-dimensional organization was somewhat disturbed due
      to air-drying. We also demonstrated that silver dots cannot be visualized in the
      reflectance mode within sections of paraffin-embedded tissues. However, their
      simultaneous demonstration in non-confocal transmitted light, together with that
      of DNA in confocal mode, appeared very useful to study their localization within
      nuclei and mitotic chromosomes.

PMID- 8288860
TI  - Combination of DNA in situ hybridization and immunocytochemical detection of
      nucleolar proteins: a contribution to the functional mapping of the human genome
      by fluorescence microscopy.
AB  - The recent application of DNA cloning and non-radioactive in situ hybridization
      techniques has strengthened the hypothesis of an ordered chromatin structure in
      interphase nuclei. The arrangement of specific chromosomal regions is not random
      and is strongly suspected to vary with functional activity. The combination of in
      situ hybridization and immunocytochemistry, allowing simultaneous detection of
      nucleic acid sequences and specific antigens in the same nucleus, has already
      made significant contributions to the study of gene expression, to simultaneous
      karyotyping and phenotyping of tumor cells, and to in situ analysis of viral
      infections. This report emphasizes the considerable interest of such combined
      techniques for functional in situ mapping of the genome at the individual cell
      level. We propose a method that combines fluorescence immunocytochemical
      detection of nucleolar proteins and fluorescence in situ hybridization of
      centromeric and telomeric probes specific for chromosome 1 in two cultured human
      cell lines. The preparative constraints for a broad application of this procedure
      are defined so that the cell preparations can be further analyzed by fluorescence
      microscopic imaging techniques and confocal laser scan microscopy. The two
      selected sequences of the human chromosome 1 can be localized in the nucleus with
      respect to nucleolar proteins in a one-step fluorescence microscopic observation.

PMID- 8288861
TI  - Ultrastructural localization of gangliosides; GM1 is concentrated in caveolae.
AB  - The ultrastructural distribution of the ganglioside GM1 was investigated in A431
      cells. After fixation, the cells were frozen in liquid nitrogen, freeze
      substituted, and then embedded in Lowicryl resin at -45 degrees C. By use of the
      cholera toxin-binding subunit adsorbed to gold as a specific probe to label on
      the sections, GM1 was shown to be present in endocytic organelles, in the trans
      Golgi network, and on the plasma membrane, but was not detectable in the
      endoplasmic reticulum. GM1 was not distributed uniformly over the plasma membrane
      but was concentrated approximately four-fold in non-coated invaginations. These
      were identified as caveolae by labeling frozen sections of cholera toxin-gold
      surface-labeled cells with antibodies to VIP-21/caveolin. The results strengthen
      the functional analogy between caveolae and sorting domains of the TGN in
      polarized epithelial cells.

PMID- 8288862
TI  - Distribution of beta-1 integrin in the developing rat heart.
AB  - Cell-cell and cell-matrix interactions play critical roles in various
      developmental processes including differentiation, proliferation, and migration.
      Members of the integrin family of cell surface components are important mediators
      of these cell-extracellular matrix (ECM) contacts or interactions. The ECM
      provides signals to individual cells essential for development and
      differentiation and plays essential roles in establishing and maintaining the
      complex structure of the vertebrate heart. Integrins provide a fundamental link
      for transduction of developmental signals to cells. Integrin expression by
      cardiac myocytes is altered during neonatal heart development and disease;
      however, little is known regarding the spatial and temporal patterns of integrin
      expression during embryonic and fetal heart development. Essential to
      understanding the role of integrins in the organization of the heart, the present
      studies have localized beta-1 integrin protein and mRNA in fetal and neonatal rat
      hearts. Beta-1 integrin is predominantly found in regions of remodeling
      (trabeculae) in the early heart (10-13 days of gestation). Later in development
      (15 days of gestation onward), beta-1 integrin is abundant in regions containing
      an elaborate ECM, such as the valves. These studies further support the
      hypothesis that the expressions of integrins and ECM are coordinately regulated
      in the developing heart.

PMID- 8288863
TI  - Localization of uric acid oxidase activity in core and matrix of peroxisomes as
      detected in unfixed cryostat sections of rat liver.
AB  - Because of controversial data in the literature, we studied the localization of
      uric acid oxidase (UAOX) activity in rat liver by light microscopy (LM) and
      electron microscopy (EM). UAOX is partially inactivated by aldehyde fixation and
      therefore we developed a technique that permits the use of unfixed cryostat
      sections for both LM and EM studies. Sections of rat liver were mounted on a
      semipermeable membrane stretched over a gelled incubation medium containing urate
      as specific substrate for UAOX and cerium ions to capture H2O2 produced by
      oxidase activity. The specificity of the reaction was checked by comparing
      incubations in the presence of substrate with incubations either in the absence
      of substrate or in the presence of substrate and 2,6,8-trichloropurine, a
      competitive inhibitor of UAOX. After incubation the sections were either fixed
      immediately for EM or visualized for LM with a second-step incubation. At the LM
      level, final reaction product was found in a granular form, homogeneously
      distributed throughout the hepatocytes. EM revealed excellent subcellular
      morphology and electron-dense reaction product in both the core and the matrix of
      peroxisomes, but not in other organelles or the cytoplasmic matrix. After
      incubations without substrate or with substrate and inhibitor, hardly any
      reaction product was found. We conclude that, because of the use of unfixed
      tissue, UAOX is not inactivated, which results in localization of UAOX activity
      not only in the core of peroxisomes but also in the peroxisomal matrix.

PMID- 8288864
TI  - Cell phenotypes and differentiative transitions in mouse submandibular salivary
      gland defined with monoclonal antibodies to mammary epithelial cells.
AB  - Recognition of distinct cell phenotypes within a given organ is important in
      defining cell relationships during development and in analyzing the role of cell
      cell and cell-matrix interactions in growth and differentiation. Phenotypic
      definition of dissociated heterogeneous cell populations is also essential for
      studies on mechanisms regulating expression of cell lineage-specific gene
      products. Mouse submandibular salivary gland (SSG) cell phenotypes in the course
      of differentiative transitions in vivo and after enzymatic dissociation in
      primary culture were defined with monoclonal antibodies (MAb) to mammary
      epithelial cells and polyclonal antibodies to functional cell products. Proacinar
      cells and differentiating and mature acinar cells were uniquely recognized by an
      MAb designated 50B8. Ductal cell components were uniquely recognized by an MAb
      designated JSE3. JSE3 immunoreactivity was particularly useful for detecting the
      emergence of two SSG duct cell phenotypes, striated ducts and the hormone
      responsive granular convoluted tubules (GCTs). JSE3-positive striated duct-like
      cells were visualized as early as Day 2 after birth and emergence of GCT-like
      structures from striated ducts was apparent between Days 10 and 11. Differential
      reactivity of acinar and ductal cells in the developing SSG with either MAb 50B8
      or JSE3 suggests the existence of intermediate progenitor cells restricted in
      their differentiation potential. An interesting pattern of immunoreactivity was
      observed with an MAb designated 33A10. During the first 2 weeks of SSG postnatal
      development, shared 33A10 immunoreactivity was observed among proacinar and
      differentiating acinar cells and all differentiating ductal segments. Coincident
      with a decrease in proliferative activity at about Day 18, 33A10 immunoreactivity
      became restricted to the GCT cell lineage before the appearance of GCT functional
      products, epidermal and nerve growth factors. Although the SSG antigen recognized
      by MAb 33A10 is presently undefined, its expression pattern suggest a molecule
      with a dual role in development and growth events and in hormone-dependent
      secretory function. Advantage was taken of the observed differential
      immunoreactivities to define the phenotypic identity of dissociated, mature SSG
      cells before and after culture. Dissociated SSG fractions enriched for either
      JSE3- or 50B8-positive cells could be maintained in short-term cultures without
      loss of expression of duct- or acinar cell-specific immunoreactivity. In addition
      to providing markers for defining dissociated SSG cells before and after culture,
      the described immunoreactivities may permit separation or enrichment of an early
      duct cell population before its commitment to a specific cell lineage. This
      approach may also provide the means to define regulatory signals involved in the
      differentiation of intermediate progenitor cells.

PMID- 8288865
TI  - Localization of angiotensin-converting enzyme (ACE) mRNA in rabbit gastric mucosa
      by in situ hybridization.
AB  - In a previous study we showed, by immunohistochemical analysis on rabbit fundic
      mucosa, that in addition to its usual presence on the luminal plasma membrane of
      endothelial cells, angiotensin converting-enzyme (ACE) was localized inside
      granules of surface and neck mucous cells and within granules of chief cells. The
      aim of the present study was to localize ACE mRNA in cells of the rabbit fundic
      mucosa by in situ hybridization with a 35S-labeled probe. This probe was a cDNA
      fragment (406 BP) encoding a portion of the rabbit ACE mRNA obtained by reverse
      transcription followed by polymerase chain reaction on total RNA extracted from
      fundic mucosa. ACE mRNAs were detected in mucous and chief cells and in
      endothelial cells of the mucosal vasculature. These results are in complete
      agreement with our prior studies which showed by immunohistochemical analysis
      that ACE is present in these cells. Our findings therefore suggest that ACE
      previously detected in epithelial cells of the rabbit gastric mucosa is actually
      synthesized within these cells.

PMID- 8288866
TI  - Ultracytochemical studies of the effects of aluminum on the blood-brain barrier
      of mice.
AB  - We studied the effect of chronic exposure (6 weeks and 6 months) of mice to
      drinking (tap) water containing 1.76% (0.06 M) aluminum lactate on some
      cytochemical properties of the blood-brain barrier (BBB). The plasmalemma-bound
      enzymatic activities of alkaline phosphatase (AP) and Ca(2+)-activated adenosine
      triphosphatase (Ca(2+)-ATPase) were studied at the ultrastructural level. Anionic
      sites were localized with cationized ferritin in a pre-embedding procedure and
      with cationic colloidal gold in a post-embedding procedure applied to brain
      samples embedded in Lowicryl K4M. Intravenously injected Evans blue and
      horseradish peroxidase (HRP) were used for evaluation of the functional state of
      the BBB. The results indicate that chronic exposure to aluminum does not
      noticeably affect barrier function of the endothelium of cerebral cortex blood
      microvessels. Focal leakage of larger than capillary microvessels (presumably
      arterioles and venules) was observed only in a few areas, such as the basal
      ganglia and amygdaloid nuclei. The localization of both enzymatic activities (AP
      and Ca(2+)-ATPase) in microvessels remained essentially unchanged. The
      localization of anionic sites was also unchanged except on the luminal surface of
      the endothelium of a few blood microvessels located in areas of the brain where
      leakage of the injected HRP was noted. In these vessels the injected HRP was
      often attached to the luminal surface of the endothelial cells, suggesting its
      increased stickiness. These data, compared with our previous observations on
      brain microvascular endothelial cells growing in vitro, indicate that
      cytotoxicity of aluminum is evidently less pronounced in the living organism,
      presumably due to action of detoxicating and regulatory mechanisms.

PMID- 8288867
TI  - Analysis of chick somite myogenesis by in situ confocal microscopy of desmin
      expression.
AB  - We explored the relationship in chick embryos between somitogenesis and the onset
      of somite myogenesis by immunodetection of the muscle-specific intermediate
      filament protein desmin. Early somite desmin expression was detected by whole
      mount in situ confocal microscopy. No detectable somite desmin was observed in
      embryos of 15 somites (Stage 12) or younger. In embryos having between 16 and 26
      somites (Stages 12-15), desmin could be detected in somites positioned
      increasingly more caudal in the embryo. Finally, in embryos of 27 somites (Stage
      16) and older, somite desmin expression was consistently present in all but the
      caudal-most six somites. Although the rate of somite formation is fairly
      constant, the rate of observed somite desmin expression progressing caudally in
      the embryo is greater initially than the rate of segmentation. After an embryo
      has formed about 27 somites, the rate of desmin appearance parallels the rate of
      segmentation at a distance of about six somites. This result suggests that very
      early somite myogenesis is not linked to somitogenesis.

PMID- 8288868
TI  - Non-isotopic in situ hybridization method for mitochondria in oncocytes.
AB  - We used in situ hybridization to specifically identify mitochondria in a series
      of formalin-fixed, paraffin-embedded oncocytic lesions. Digoxigenin-labeled DNA
      probes were generated by the polymerase chain reaction (PCR), with primers
      designed to amplify a mitochondrion-specific 154 BP sequence within the ND4
      coding region. Probes were hybridized with mitochondrial DNA under stringent
      conditions. Oncocytes were strongly and consistently stained, reflecting the high
      copy number of mitochondrial DNA within these cells. Because of the presence of
      endogenous biotin within mitochondria, digoxigenin is preferable to biotin as a
      label for detection of mitochondria.

PMID- 8288869
TI  - A simple dot-immunobinding assay for quantification of synaptophysin-like
      immunoreactivity in human brain.
AB  - Neocortical decreases in synaptic density correlate significantly with the
      cognitive impairment seen in Alzheimer disease. Recently available monoclonal
      antibodies (MAb) have made possible the highly specific and sensitive detection
      of synapse-associated proteins in immunocytochemical and immunochemical
      techniques. We describe a simple yet highly sensitive dot-immunobinding assay for
      relative quantification of the synapse marker protein synaptophysin in human
      brain homogenate fractions with the mouse MAb SY38. Fractions prepared from
      control and Alzheimer specimens were blotted to nitrocellulose membranes and
      reacted with SY38, rabbit secondary antibody, and iodinated protein A. A relative
      standard curve was constructed to normalize results from multiple assay runs. We
      correlated the results with the more complex immunocytochemical synaptic density
      measurement technique of immunolabeling coupled with laser confocal imaging,
      showing good correlation at r = 0.821. Results from Alzheimer cases showed a 40%
      decrease in synaptophysin immunoreactivity in midfrontal cortex compared with
      normal controls.

PMID- 8288870
TI  - Rapid in vitro micro-cytotoxicity tests for the detection and quantitation of
      neutralizing antibodies to both viruses and toxins.
AB  - A generally applicable method was developed for the rapid and quantitative
      detection of both toxin- and virus neutralizing antibodies. The method was
      optimized for three different biological agents, i.e., Shigella toxin, influenza
      viruses (A/Beying, A/Taiwan and B/Yamagata) and Chikungunya virus. The in vitro
      micro-cytotoxicity tests developed for the detection and quantitation of
      neutralizing antibodies are based on the inhibition of the virus- or toxin
      induced cytotoxic effect by antibodies. As a result of the cytotoxicity, infected
      cells are no longer attached to the solid phase and can be easily removed.
      Thereafter, the proteins of the remaining living cells are stained. After
      removing the excess dye, the remaining dye is dissolved and the absorbance values
      are measured. The neutralization titers are determined from the absorbance
      values. Since the tests are performed in wells of microtiter plates, the in vitro
      micro-cytotoxicity tests are less laborious and consume less reagent in
      comparison with classical neutralization tests.

PMID- 8288871
TI  - A simple method for the evaluation of receptor binding capacity of modified
      cytokines.
AB  - We have developed a flow cytometric method to evaluate the binding of interleukin
      2 analogues to receptors. The method relies on competition for binding between a
      fluorescein-conjugated monoclonal antibody (MoAb) directed against the human
      interleukin-2 receptor alpha chain (fluorescein isothiocyanate (FITC) anti-IL-2R)
      and the test protein. IL-2R positive cells are incubated with FITC-anti-IL-2R
      MoAb in the presence of native IL-2 or IL-2 iodinated by either the chloramine-T
      or the lactoperoxidase-glucose-oxidase method. The binding of IL-2 is indicated
      by decreased fluorescence. This method is suitable for measuring the binding
      capacity of modified IL-2 molecules and avoids the need for radioactive tracers.
      It provides a simple and reproducible technique, which can be extended readily to
      the study of the receptor binding capacity of cytokines conjugated with toxins,
      drugs or other molecules.

PMID- 8288872
TI  - Measurement of eosinophil cationic protein (ECP) and eosinophil protein
      X/eosinophil derived neurotoxin (EPX/EDN). Time and temperature dependent
      spontaneous release in vitro demands standardized sample processing.
AB  - The measurement of eosinophil derived proteins such as eosinophil cationic
      protein (ECP) and eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN) in
      biological fluids may be a useful indicator of eosinophil activity in ongoing
      inflammatory processes. This study was performed on blood samples and illustrates
      that serum values of ECP in particular, but also of EPX, are mainly a result of
      spontaneous release during the processing of blood samples. In the presence of
      divalent cations (Ca2+ and Mg2+), the amount of released ECP and EPX is dependent
      upon the incubation temperature and the time before centrifugation and recovery
      of serum. Moreover, the utensils used for blood sampling may influence the serum
      levels of ECP and EPX. Thus, standardized sample processing is of paramount
      importance if the results are to have optimal diagnostic or clinical value.

PMID- 8288873
TI  - The assessment of different methods of data reduction for qualitative assays.
AB  - An increasing number of biochemical tests for the detection of ailments such as
      hepatitis, AIDS, listeria poisoning etc are becoming qualitative in nature since
      the concern is over whether contamination is present or not rather than to what
      degree it is present. Many tests have an underlying quantitative scale that is
      dichotomised by the calculation of a detection limit, whereby a result is deemed
      negative, say, if its assay response is less than the detection limit and
      positive otherwise. A number of methods have been proposed for determining the
      detection limit and a few authors have tried to compare some of these methods. To
      date, as far as we are aware, these comparisons have been neither exhaustive nor
      conclusive. We propose a comparison criterion based on the false positive and
      false negative rates and use this criterion to assess five different methods via
      a simulation study. For the simulation model used, under the conditions imposed,
      we conclude that a detection limit based on control samples is probably the most
      efficient. Each method of calculating the detection limit has a coefficient
      associated with it for determining the exact position of the detection limit. The
      criteria, to date, for selecting the value of this coefficient seem arbitrary
      since whole numbers are often quoted, presumably reflecting convenience. Our
      simulation approach provides a possible method for determining the value of the
      coefficient which gives rise to a specified false positive or false negative
      rate.

PMID- 8288874
TI  - Similar frequencies and kinetics of cytokine producing cells in murine peripheral
      blood and spleen. Cytokine detection by immunoassay and intracellular
      immunostaining.
AB  - Production of IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IFN-gamma, GM-CSF (granulocyte
      macrophage colony stimulating factor) and macrophage colony stimulating factor by
      murine peripheral blood and spleen cells was analyzed following primary and
      secondary mitogen stimulation in vitro. Individual cytokine producing cells were
      detected by an intracytoplasmic staining technique. Cytokine production in cells
      from peripheral blood and spleen was comparable and more rapidly induced by
      calcium ionophore and phorbol 12-myristate 13-acetate than by concanavaling A.
      Restimulation in vitro induced both a swift production of cytokines and, for some
      cytokines, higher frequencies of producing cells. This was especially evident for
      IL-10 secreting cells, which increased 30-80 times in secondary responses. These
      analyses using the dual approaches of immunoenzymetric and fluorescent
      immunohistochemical techniques provide important evidence that cytokine induction
      kinetics can differ following primary or secondary stimulation.

PMID- 8288875
TI  - Measurement of membrane bound IgD and IgM on B lymphocytes.
AB  - An assay system for the determination of the membrane bound IgD (mIgD) and IgM
      (mIgM) on B lymphocytes was developed by the combination of two new ELISA methods
      with the results of flow cytometry after labeling with specific antibodies. The
      mIgD and mIgM of B lymphocytes were prepared by incubating mononuclear cells
      (MNCs) in Tween 20 containing buffer and repeated freeze/thaw cycles. Optimal
      results were achieved with 0.2-0.4% Tween 20 and two freezing cycles. With biotin
      streptavidin amplification the sensitivity of the ELISA was 30 microU/ml for IgD
      and 0.5 ng/ml for IgM. In healthy persons 3.5 +/- 0.5 mU mIgD were detected on
      10(6) IgD+ cells and 57.1 +/- 5.9 ng mIgM on 10(6) IgM+ cells. The mIgD/mIgM
      ratio was 0.065 +/- 0.005 mU/ng. The developed ELISA systems utilize only
      commercially available reagents and therefore provide a convenient reproducible
      tool for determining membrane bound IgD and IgM on B lymphocytes.

PMID- 8288876
TI  - An improved model for the examination of biological effects of locally
      administered cytokines.
AB  - Cytokines incorporated into agarose blocks and implanted subcutaneously into mice
      establish an in vivo gradient which can be used to mimic a local inflammatory
      process. We have developed a model in which cellular influx into cytokine
      impregnated blocks parallels the normal cellular reaction to infections or
      wounds. Agarose blocks containing supernatants from ConA activated rat spleen
      cells attracted neutrophils within 4 h. These cells were followed by lymphocytes
      and macrophages in 24 h. Flow cytometry analysis of lymphoid cells on day 1
      revealed that 38% were Ig+ (B cell marker), 60% MAC-2,3+ and 20% Thy 1.2+ of
      which only a small fraction were expressing CD4 on their surface. These numbers
      changed with time following implantation of the blocks. Initially, isolated
      adherent cells (macrophages) were resting, with low phagocytic activity. Cells
      isolated from blocks at later time points were activated, as evidenced by their
      increased ability to ingest fluoresceinated beads. The secretion patterns of
      cells trafficking to murine rIL-1 containing agarose blocks were examined. TNF,
      IL-6 and antibody secreting cells were found. No IL-2 was detected at any time.
      We believe that this model will be of value in studies of local actions of
      cytokines.

PMID- 8288877
TI  - A fluorescence-based quantitative adhesion assay to study interactions between
      Entamoeba histolytica and human enterocytes. Effect of proinflammatory cytokines.
AB  - In order to study the initial events during infection of target cells by the
      enteric pathogen Entamoeba histolytica, we developed a quantitative adhesion
      assay based on the use of a human colonic cell line (CaCo-2) and biotinylated
      amoebae tagged with fluorescein. To prevent the strong and rapid lytic activity
      of Entamoeba histolytica on colonic cells, which would otherwise impede the study
      of the primary adhesion steps, parasites were mildly fixed, biotinylated and
      labelled with streptavidin-FITC. After labelled parasites have bound to
      enterocytes, nonadhered amoebae are removed by washing and attached parasites
      quantified by means of an automated fluorescence plate reader. The bioassay is
      simple, nonhazardous and can be completed in 1.5 h. We were able to detect ranges
      from 200 to 20,000 fluorescent parasites per microwell in a 96-well plate,
      containing approximately 10(5) colonic cells. Fluorescence intensity (arbitrary
      units) increased in direct relationship to the number of parasites added per
      well, and was not limited by the size of the culture plate (96, 24 or six wells).
      As an example of the value of this assay, two proinflammatory cytokines
      (interleukin-1, (IL-1 beta) and interferon-gamma (IFN-gamma) known to influence
      the adhesion properties of endothelial and epithelial cells, were used to assess
      their effects upon enterocyte-entamoeba binding. The increase in amoebae binding
      revealed by cytokine treatment to enterocytes suggests that the parasite may take
      advantage of inflammatory stimuli in order to increase its binding to colonic
      epithelium. We believe this rapid, sensitive and simple method offers the
      potential for large scale screening assays to study the immunobiology of this
      protozoal infection by analysing the mechanisms involved in the primary
      interactions between Entamoeba histolytica and enterocytes.

PMID- 8288878
TI  - Quantitative analysis of platelet-activating factor in human plasma. Application
      to patients with liver cirrhosis and disseminated intravascular coagulation.
AB  - A simple and reliable analytical procedure was developed for determination of
      platelet-activating factor (PAF) in human plasma using radioimmunoassay (RIA).
      The assay system consisted of lipid extraction with 2-propanol, lipid separation
      by Amprep octadecyl minicolumn chromatography and thin-layer chromatography and
      RIA (charcoal method), and was suitable for quantitation of 30-1000 pg of PAF.
      The sensitivity of RIA for PAF was notably higher than that for sn-2-short-chain
      PAF-like phosphatidylcholines. This assay system was then applied for measurement
      of PAF in human plasma. The normal level of plasma PAF was 54 +/- 40 pg/ml (n =
      35), whereas plasma PAF levels in patients with liver cirrhosis (LC) and
      disseminated intravascular coagulation (DIC) were significantly elevated to 238
      +/- 314 pg/ml (n = 14) and 591 +/- 328 pg/ml (n = 14), respectively. The values
      obtained using this assay system were comparable to those obtained by gas
      chromatography/mass spectrometry analysis and bioassay. These results indicate
      that our new assay system is useful for determining changes in the level of
      plasma PAF associated with diseases such as LC and DIC.

PMID- 8288879
TI  - New procedure for the detection of complement deficiency by ELISA. Analysis of
      activation pathways and circumvention of rheumatoid factor influence.
AB  - A procedure using enzyme-linked immunosorbent assays for the assessment of
      complement function has been evaluated. The sera investigated were incubated in
      microtiter plates with solid-phase complement activators. Human polyclonal IgG or
      monoclonal IgM were used for classical activation pathway assays and Salmonella
      typhosa lipopolysaccharide (LPS) for alternative activation pathway assays. The
      analysis focussed on deposition of C9 and properdin as detected with enzyme
      conjugated antibodies. In an attempt to avoid spurious results due to rheumatoid
      factors in patient sera, monoclonal mouse and chicken antibodies were
      unsuccessfully tested as indicator reagents in the assay with solid-phase IgG.
      However, the use of solid-phase IgM as an activator completely circumvented the
      influence of rheumatoid factors. With solid-phase IgG or IgM, properdin
      deposition occurred in the absence of factor D. A combination of assays is
      suggested for diagnostic purposes: IgM-coated plates with detection of bound C9
      and properdin for the classical pathway and LPS-coated plates with detection of
      bound properdin for the alternative pathway. The procedure distinguished between
      defects of the classical activation pathway (C1, C4, C2), the alternative
      activation pathway (C3, factor B, factor D, properdin) and the terminal
      components (C5-C9). This analytical approach may be useful for detection of
      inherited complement deficiency and the assessment of complement function in
      acquired complement deficiency states.

PMID- 8288880
TI  - Liposomes as vaccine carriers. Incorporation of soluble and particulate antigens
      in giant vesicles.
AB  - Giant liposomes (mean diameter 5.5 microns) composed of egg phosphatidylcholine
      or distearoyl phosphatidylcholine, phosphatidyl glycerol, cholesterol and
      triolein were prepared by a double emulsion technique. They were then mixed with
      model particulate (killed Bacillus subtilis, and killed Bacille Calmette-Guerin)
      and soluble (tetanus toxoid) vaccines and freeze-dried. Rehydration of the powder
      resulted in the generation of vesicles of similar mean diameter and diameter
      range, containing up to 27% (mean value) of the materials used for entrapment.
      Separation of entrapped from non-entrapped material was carried out by sucrose
      gradient centrifugation (B. subtilis and BCG) or centrifugation at 600 x g
      (toxoid). Light microscopy of liposomes containing B. subtilis labelled with
      fluorescein isothiocyanate revealed the presence of bacteria in individual
      vesicles which, in separate studies, were also found to entrap latex particles
      (0.5 and 1.0 micron diameter). Bacteria-containing liposomes could be freeze
      dried in the presence of trehalose with most (83-87%) of the entrapped material
      recovered within the vesicles on reconstitution with saline. Liposomes were also
      shown to retain quantitatively their content of B. subtilis and, to a lesser
      extent, toxoid in the presence of mouse plasma at 37 degrees C and in situ after
      intramuscular injection into mice, for up to 24 h. Since liposomes are known
      (Gregoriadis, G. (1990) Immunol. Today 11, 89) to act as immunological adjuvants
      and vaccine carriers, giant vesicles containing microbes (live or attenuated if
      needed since the conditions of entrapment are mild) and, when appropriate,
      soluble antigens, could be used as multiple vaccines to ensure simultaneous
      presentation of antigens to immunocompetent cells.

PMID- 8288881
TI  - The role of pH in modified ELISA procedures used for the estimation of functional
      antibody affinity.
AB  - Solid phase assays for the measurement of functional antibody affinity are
      increasingly being used in both clinical and research settings. The majority of
      such assays employ a chemical reagent to disturb antibody binding but relatively
      little is known about the properties of such reagents and the basis of their
      effect on antigen-antibody binding. We have evaluated the diethylamine (DEA)
      ELISA procedure for the measurement of functional antibody affinity in two
      independent assays, one for functional human IgG subclass affinity to an
      organism, Moraxella catarrhalis, and the other for measuring functional affinity
      of mouse monoclonals specific for the cat allergen Fel d I. DEA was shown to
      increase the pH of the buffering solution and it was this rise in pH that
      affected antibody binding. Alkaline buffer and DEA were equally efficient in the
      inhibition of binding of both the human IgG subclasses and the two mouse
      monoclonal antibodies to the solid phase. In contrast, pH was shown to have no
      role in the chaotropic effect of the ion, thiocyanate.

PMID- 8288882
TI  - Selective destruction of contaminating cells in monolayer cultures.

PMID- 8288883
TI  - TITRECAL: an MS-DOS program for automated calculation of antibody titres from
      ELISA data.
AB  - This software package was written to semi-automate the routine calculation of
      antibody titres from ELISA data without standards, by fitting the data to a
      generalised four parameter logistic curve. Data recording from a plate reader by
      direct serial interface to a diskfile is also facilitated.

PMID- 8288884
TI  - ELEASY: a program for processing experimental enzymoimmunoassay data.
AB  - A computer program is described that automates processing of data from enzyme
      immunoassays. This includes statistics, data editing, graphic display and fitting
      of data to both a straight line and a sigmoidal curve. The program can work
      either without the need for the user to enter choices, initial values, etc., or
      else with user-controlled choices for adaptation to special data sets.

PMID- 8288885
TI  - A new human cell line for the molecular dissection of the requirement for
      interleukin-1 in the production of interleukin-2 by immature T cells.
AB  - An immature human T cell line, PER-117, can be induced to secrete interleukin-2
      (IL-2). In contrast to mature T cells or the Jurkat cell line, PER-117 cells
      require interleukin-1 (IL-1) for optimal IL-2 secretion, in addition to calcium
      ionophore and phorbol 12-myristate 12-acetate (PMA). These requirements mirror
      the conditions reported to be optimal for normal immature T cell receptor (TCR)
      negative thymocytes. IL-1 did not substitute for either of the other signals
      required for IL-2 production, i.e., calcium ionophore or PMA, suggesting that IL
      1 activates pathways different from those elicited by the two other stimuli. For
      optimal effect, IL-1 needed to be provided at the same time as the two other
      signals. Significantly, a signal provided by a low concentration of PMA (not
      leading to IL-2 induction by itself in the presence of calcium ionophore) was
      necessary. The studies reported here provide the first evidence that three
      signals are required for optimal IL-2 production in a human immature T cell line.
      PER-117 cells produce substantial levels of IL-2 and thus provide a model to
      study stage-specific signal transduction and transcriptional activation of the IL
      2 gene in IL-1 responsive immature thymocytes.

PMID- 8288886
TI  - Influence of solid-phase antigen in competition enzyme-linked immunosorbent
      assays (ELISAs) on calculated antigen-antibody dissociation constants.
AB  - The competition ELISA method described in 1985 by Friguet and colleagues has
      frequently been used to determine dissociation constants (KD) of antigen-antibody
      reactions. Subsequently Stevens suggested a correction for the bivalency of IgG.
      In either case, the KD is assumed to vary only with the composition of competing
      fluid-phase antigen and consequently should not be affected by the solid-phase
      antigen. However, during the course of experiments defining epitopes to the V3
      loop of human immunodeficiency virus type 1, both the composition and density of
      solid-phase antigen were capable of significantly influencing the calculated
      values. With one solid-phase antigen, the calculated KD was a function of antigen
      density. With a second solid-phase antigen, the calculated KD did not vary with
      the density. With the latter antigen or with low densities of the former, KDs
      calculated using the Stevens correction for bivalency were close to the estimate
      obtained by a radiolabeled peptide precipitation assay. Accordingly, since the
      density and composition of solid-phase antigen may alter the KD calculated from
      competition ELISAs, such estimates should be confirmed by a more readily
      interpretable immunological method.

PMID- 8288887
TI  - An ultrasensitive chemiluminoenzyme immunoassay for the quantification of human
      tissue kininogens: application to synovial membrane and cartilage.
AB  - A sandwich enzyme immunoassay using a chemiluminescent detection has been
      developed for the quantification of total human (high and low molecular weight)
      kininogens in tissue extracts. This assay uses monospecific polyclonal IgG
      labelled with alkaline phosphatase and the commercially available dioxetane
      derivatives as substrates, for the detection of immune complexes. This method
      exhibits a sensitivity level of 1 fmol/ml and allows a precise quantification of
      total kininogens in synovium and cartilage extracts. When characterized by
      Western blot, the immunoreactive material reveals the presence of both high and
      low molecular weight kininogens.

PMID- 8288888
TI  - Induction of plasmacytomas that secrete monoclonal anti-peptide antibodies by
      retroviral transformation.
AB  - ABL-MYC, a retrovirus that coexpresses v-abl and c-myc, was used to infect six
      BALB/c mice that had been immunized twice with a KLH-conjugated peptide that
      consisted of the 18 carboxyterminal amino acids of protein kinase C-eta (PKC
      eta). All mice developed transplantable, monoclonal plasmacytomas, and five out
      of six plasmacytomas secreted antigen-specific antibodies, even after
      transplantation. All these antibodies recognized PKC-eta on Western blots of
      crude cell lysates and did not cross react with other isoforms of the PKC family.

PMID- 8288889
TI  - Production of large amounts of recombinant interleukins by cDNA transfected mouse
      myeloma cells cultured in dialysis tubing.
AB  - Studies of interleukin function often require large quantities of these highly
      expensive substances. The available interleukins are generally recombinant
      proteins produced in bacteria or yeast and, less commonly, interleukins produced
      by mammalian cells, which provide appropriate glycosylation and other post
      translational modifications. Due to differences in biosynthesis, difficulties in
      production and purification the quality of the interleukin preparations may vary.
      We have taken advantage of the recently developed constitutively interleukin
      secreting mouse myeloma cell lines and the dialysis tubing culture technique,
      which permit cells to be grown at high densities, in order to establish a method
      for the production of large amounts of recombinant murine IL-2 and IL-4. We show
      that these interleukins can be produced at low cost and in concentrations 20-30
      fold higher than in conventional culture flasks. A single dialysis tubing culture
      will produce more than 10(6) U of interleukin which may be compared with the
      available commercial preparations containing between 10- and a 100-fold less per
      vial. The IL-2 and IL-4 produced in this manner are biologically active molecules
      as demonstrated by the strong proliferative response of clonal T cells and the
      isotype-switching effect in LPS-stimulated splenic B cell cultures. The dialysis
      tubing culture technique is a simple and highly cost-effective means of
      generating large quantities of biologically active interleukins and is especially
      suitable for research laboratories interested in functional studies of these
      proteins.

PMID- 8288890
TI  - A high-capacity manifold support for the detection of specific IgE antibodies in
      allergic individuals.
AB  - A high-capacity manifold support with immobilized antigen was developed for the
      analysis of IgE-mediated immune reactivity in allergic subjects. Using this 96
      pronged support, specific antibodies were trapped and detected from large sets of
      serum samples. We describe the binding of large amounts of antigen onto the
      expanded surface of the manifold support, permitting efficient identification of
      allergic individuals.

PMID- 8288891
TI  - Development of an ELISA for measuring the activity of tetanus toxoid in vaccines
      and comparison with the toxin neutralization test in mice.
AB  - An enzyme-linked immunosorbent assay (ELISA) has been developed to measure anti
      tetanus toxoid antibody levels in immunized guinea-pig sera as a useful
      alternative to the currently used toxin neutralization test (TNT) in determining
      the activity of the tetanus toxoid in vaccines. The ELISA was found to measure
      antibody levels as low as 5.8 x 10(-5) IU/ml. Furthermore, a comparison of the
      results from ELISA and TNT involving 132 different commercial vaccines showed a
      very good correlation (r = 0.94, p < 0.001) between antibody levels measured by
      both methods. The results suggest that the proposed ELISA is a reliable, simple
      and economical alternative to the TNT in mice for assessing the activity of
      tetanus toxoids in vaccines.

PMID- 8288892
TI  - Restoration of a normal level of immunoglobulin production in a hybridoma cell
      line following modification of the chromosomal immunoglobulin mu gene by gene
      replacement.
AB  - In the present investigation, we have measured the levels of IgM mRNA and protein
      in recombinant cell lines in which the chromosomal immunoglobulin mu gene has
      been modified by gene replacement (gene conversion or double reciprocal
      recombination) or vector integration (single reciprocal recombination) events.
      Our studies reveal that chromosomal immunoglobulin mu genes modified by gene
      replacement are expressed at wild-type levels whereas those modified by vector
      integration have lower levels of immunoglobulin mu gene expression. These results
      suggest that gene replacement may a preferred method for the construction of
      hybridoma and myeloma cell lines producing optimized immunoglobulins and for
      studies of immunoglobulin gene function.

PMID- 8288893
TI  - A new, simple, bioassay for human IFN-gamma.
AB  - IFN-gamma induces the production of N-formyl-kynurenine from L-tryptophan in
      various cell types by the induction of the enzyme indoleamine 2,3-dioxygenase
      (IDO). The IFN-gamma induced IDO activity in the glioblastoma cell line 86HG39
      and cells of clone 2D9 derived from this cell line was found to be greater than
      that in Hela cells and U373MG cells. Consequently 2D9 cells were used in all
      subsequent experiments. The determination of kynurenine in the supernatant of IFN
      gamma activated cells was performed photometrically using a microplate reader. It
      was found that the amount of kynurenine produced was directly proportional to the
      amount of IFN-gamma used to activate cells. The detection limit for IFN-gamma of
      this assay was 20 U/ml. The induction of L-tryptophan degradation was specific
      for IFN-gamma since neither IFN-alpha, IFN-beta, IL-1, IL-2, IL-6, GM-CSF nor TNF
      alpha induced the production of detectable amounts of kynurenine by 86HG39 and
      2D9 cells. Furthermore, a mab directed against IFN-gamma was able to completely
      block the IFN-gamma induced IDO activation. This bioassay was used to determine
      the IFN-gamma content of supernatants harvested from toxoplasma antigen specific
      human T cell lines and clones. This assay gave reproducible results which
      correlated well with the IFN-gamma content detected in the same samples using a
      commercially available ELISA kit. Furthermore in the case of T cell supernatant
      stimulated 2D9 cells a mab directed against IFN-gamma was able to completely
      block IDO induction. We conclude that the measurement of kynurenine production
      induced by IFN-gamma can be used to determinate IFN-gamma content. This is a
      simple bioassay which can be performed with standard laboratory equipment.

PMID- 8288894
TI  - A sensitive and specific bioassay for the detection of human interleukin-10.
AB  - Interleukin-10 (IL-10) is a novel cytokine that is produced by T cells,
      macrophages, B cells and keratinocytes. It has been shown to inhibit cytokine
      production and proliferation by T cells when macrophages are used as accessory or
      antigen presenting cells. Monokine production by macrophages is effectively
      downregulated by IL-10 and it can be used as a growth factor by CD4, CD8 and
      gamma/delta positive T cells as well as mast cells and B cells. It is because of
      these pleiotropic immunoregulatory effects that the detection of IL-10 in the
      supernatants of T cells, B cells, macrophages and other cells is important for
      many scientific questions. Here we describe a simple and sensitive bioassay
      specific for human IL-10 using the IL-10 dependent growth of the mouse mast cell
      line D36. Our data show that this assay is not crossreactive with hIL-1 beta, hIL
      2, hIL-3, hIL-4, hIL-5, hIL-6, hIL-9, hIL-12, hGM-CSF and hTNF-alpha and that it
      can be completely blocked by an antibody against human IL-10. The hIL-10 induced
      growth of the D36 cell line is dependent on the presence of mIL-4. Human IL-10
      can be measured in a concentration range from approximately 10 U/ml to 0.05 U/ml.
      This assay is only of limited use for the measurement of IL-10 in human blood
      samples since it is inhibited by the presence of human serum.

PMID- 8288895
TI  - Detection of anti-helminth antibody by microenzyme-linked immunosorbent assay
      using recombinant antigen and anti-beta-galactosidase monoclonal antibody.
AB  - An enzyme-linked immunosorbent assay (ELISA) using antigenic beta-galactosidase
      helminth derived recombinant fusion protein (FP) obtained by the recombinant DNA
      technique provided a useful diagnostic tool for human helminthiasis. Helminth
      infected human sera reacted strongly with FP that was immobilized with anti-beta
      galactosidase monoclonal antibody on microplates. However, FP did not react with
      sera from patients with other helminthiases. In detection of anti-helminth IgG
      antibody, the present ELISA system using FP and anti-beta-galactosidase
      monoclonal antibody was highly specific compared to that using biochemically
      extracted soluble antigens.

PMID- 8288896
TI  - A novel and sensitive method for the detection of secreted cell products using
      time-resolved fluorescence.
AB  - A new test has been developed for the quantitative detection of products secreted
      from isolated cells, based on the use of lanthanide- rather than enzyme-linked
      streptavidin. Used as a label, europium (Eu3+) can be measured with high
      sensitivity by time-resolved fluorescence. The main advantages of this assay are
      both an increased sensitivity and measuring range of cell released substances,
      when compared to the standard "wet" ELISA. Thus, the immunoglobulin secretion
      rate of 10(5) splenocytes could be easily measured by time-resolved
      fluoroimmunoassay (TR-FIA), while it remained below the detection limit of the
      'wet' ELISA. In contrast to the classical ELISPOT test, this assay does not
      detect single antibody secreting cells (ASC), but would be useful for precise
      quantification of secreted cell products, such as immunoglobulins, cytokines,
      growth factors.

PMID- 8288897
TI  - Production of lymphotoxin (LT alpha) and a soluble dimeric form of its receptor
      using the baculovirus expression system.
AB  - Human LT alpha and a fusion protein (p60:Fc) comprised of the extracellular
      domain of the 60 kDa TNF receptor (TNFR60) fused to the Fc portion of human IgG1
      were produced in insect cells infected with recombinant baculoviruses. The p60:Fc
      fusion produced in insect cells accumulates in culture supernatants to levels > 2
      mg/l. Purified p60:Fc binds human TNF and LT alpha with high affinity (200-600
      pM) and neutralizes TNF cytolytic activity at equimolar stoichiometric
      concentration. The data show that p60:Fc is an effective ligand-precipitating
      reagent which recognizes recombinant LT alpha produced in mammalian or insect
      cells and naturally occurring LT alpha produced in T cells. The levels of human
      LT alpha produced in baculovirus-infected insect cells is estimated to be
      approximately 20 mg/l. Insect cell-derived human LT alpha is biologically active
      in an L929 cytotoxicity assay and is efficiently neutralized by p60:Fc. These
      data demonstrate that the baculovirus system is useful for overexpressing
      biologically active LT alpha and p60:Fc and therefore, may be applicable to other
      oligomeric cytokines and soluble dimeric cytokine receptors.

PMID- 8288898
TI  - Quantification of recombinant human interleukin-1 alpha by a specific two cell
      immunobioassay.
AB  - The detection of picogram quantities of recombinant human IL-1 alpha in human and
      rat serum was accomplished by a sensitive and specific two cell immunobioassay.
      The specificity is provided by an IL-1 alpha specific mouse IgM monoclonal
      antibody which is non-neutralizing thus allowing for the addition of the EL-4 NOB
      1 cell line directly to the IL-1 alpha monoclonal antibody complex. The above
      cell line is then converted to an IL-2 producer line in response to the captured
      IL-1 alpha. Supernatant from the EL-4 NOB-1 cells is then added to the IL-2
      dependent CTLL-2 line and cell proliferation measured by thymidine incorporation.
      This assay has the advantage of specificity provided by the antibody capture
      step, sensitivity provided by the EL-4 NOB-1 line (1-50 pg/ml) and finally ease
      of maintenance of the responder cell line which requires no feeder cells or
      mitogens. Data are reported on the sensitivity, precision, reproducibility and
      specificity of the assay, the stability of rhIL-1 alpha in serum and the recovery
      of rhIL-1 alpha from serum. We also report on the use of this procedure to assay
      samples from rats given ascending doses of rhIL-1 alpha.

PMID- 8288899
TI  - Affinity ranking of influenza neuraminidase mutants with monoclonal antibodies
      using an optical biosensor. Comparison with ELISA and slot blot assays.
AB  - A recently developed alternative to the more traditional techniques for studying
      antigen-antibody interactions has been examined. This method involves the use of
      an optical biosensor employing surface plasmon resonance detection. In this
      system one of the reactants is immobilized on the sensor surface and other
      reactants are passed over the sensor surface sequentially at a constant flow
      rate. Binding phenomena are detected in real time from changes in the angle at
      which surface plasmon resonance occurs. This is dependent, among other things, on
      changes in the refractive index (which is directly proportional to the mass) at
      or near to the sensor surface. Applications of this biosensor technique for
      comparing the binding of related neuraminidases, purified from escape mutants of
      influenza virus NWS/G70C/75 (N9), to two antibody Fab fragments, are described.
      These results were compared with those obtained from ELISA and slot blot assays
      on the same neuraminidases interacting with the same two monoclonal antibodies.
      The biosensor method was shown to be highly specific, permitting rapid screening
      of binding in such antigen-antibody systems.

PMID- 8288900
TI  - Intracellular accumulation of collagen VII in cultured keratinocytes from a
      patient with dominant dystrophic epidermolysis bullosa.
AB  - Expression of collagen VII, a candidate molecule for dystrophic epidermolysis
      bullosa, was analyzed in cultured keratinocytes from a patient with generalized
      dominant dystrophic epidermolysis bullosa (DEBD) of the Pasini subtype. Double
      immunofluorescence revealed an increased intracellular staining of collagen VII
      that co-localized with protein disulfide isomerase, a marker of the rough
      endoplasmic reticulum. Ultrastructural analysis of cultured DEBD cells showed
      dilated cisternae of the rough endoplasmic reticulum and numerous residual
      bodies, both of which contained abundant collagen VII as detected by
      immunoelectron microscopy. Immunoblotting of keratinocyte extracts indicated an
      increased ratio of cell-associated versus secreted soluble collagen VII in DEBD
      cells. Collagen VII mRNA was of normal size in the DEBD cells, but present in
      excessive amounts. The data suggest a mutation in the collagen VII gene that
      leads to intracellular accumulation and degradation of this collagen, and thus to
      a reduced number of anchoring fibrils at the dermo-epidermal junction, and
      subsequently to blistering of the skin in this family.

PMID- 8288901
TI  - Molecular markers of retinoid activity in skin.

PMID- 8288902
TI  - Basal detachment of the epidermis using dispase: tissue spatial organization and
      fate of integrin alpha 6 beta 4 and hemidesmosomes.
AB  - Dispase has been utilized to produce basal detachment of the epidermis of human
      skin biopsies and to study the consequences induced afterwards during incubations
      of the detached tissue. Spatial reorganization of the epidermis is observed under
      these conditions and is characterized by disappearance of the typical basal
      keratinocyte layer. Immunofluorescent labelings reveal upward migration of
      several cells exhibiting the basal phenotype between suprabasal differentiating
      keratinocytes and demonstrate progressive intracellular expression of
      hemidesmosomal components: the integrin alpha 6 beta 4 and two plaque components,
      the 230-kDa bullous pemphigoid antigen and HD1, a 500-kDa protein. Using electron
      microscopy and immunogold techniques, we demonstrate that the hemidesmosome
      containing basal membrane domains enter the cell cytoplasm after detachment of
      the epidermal tissue. Partial recycling of internalized hemidesmosomal components
      is also suggested. Our findings illustrate the processing of released
      hemidesmosomes in detached basal keratinocytes and suggest some heterogeneity
      between basal cells migrating towards a suprabasal position and those remaining
      in the basal layer. These results suggest that the dispase-detached epidermis is
      a self-remodeling tissue in which basal keratinocytes' and tissue's polarities
      observed in the anchored epidermis are progressively changing.

PMID- 8288903
TI  - Inhibition of collagen lattice contraction by pentoxifylline and interferon
      alpha, -beta, and -gamma.
AB  - The ability to control wound contraction is important in preventing disfiguring
      scarring in burn and trauma patients. Fibroblasts within the wound generate the
      mechanical forces that cause this contraction, and their interactions with
      various extracellular matrix components are thought to regulate this process.
      Because pentoxifylline and the interferons are believed to moderate fibroblast
      production of such matrix components, we assessed the effects of these agents on
      wound contraction in vitro, using a model wherein dermal fibroblasts are
      incorporated into a collagen lattice. Pentoxifylline and interferon-alpha, -beta,
      and -gamma inhibited lattice contraction in a dose-dependent manner and showed no
      effect on cell number or cell viability. These results suggest that
      pentoxifylline and the interferons may retard wound contraction in vivo and thus
      reduce scarring associated with severely contracted wounds. Further study is
      needed to determine the mechanism of action of these agents on the collagen
      lattice model.

PMID- 8288904
TI  - Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin.
AB  - We measured enzymic and non-enzymic antioxidants in human epidermis and dermis
      from six healthy volunteers undergoing surgical procedures. Epidermis was
      separated from dermis by curettage and antioxidants were measured by high
      performance liquid chromatography (HPLC) or standard spectrophotometric methods.
      The concentration of every antioxidant (referenced to skin wet weight) was higher
      in the epidermis than in the dermis. Among the enzymic antioxidants, the
      activities of superoxide dismutase, glutathione peroxidase, and glutathione
      reductase were higher in the epidermis compared to the dermis by 126, 61 and
      215%, respectively. Catalase activity in particular was much higher (720%) in the
      epidermis. Glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase, which
      provide reduced nicotinamide adenine dinucleotide phosphate (NADPH), also showed
      higher activity in the epidermis than the dermis by 111% and 313%, respectively.
      Among the lipophilic antioxidants, the concentration of alpha-tocopherol was
      higher in the epidermis than the dermis by 90%. The concentration of ubiquinol 10
      was especially higher in the epidermis, by 900%. Among the hydrophilic
      antioxidants, concentrations of ascorbic acid and uric acid were also higher in
      the epidermis than in the dermis by 425 and 488%, respectively. Reduced
      glutathione and total glutathione were higher in the epidermis than in the dermis
      by 513 and 471%. Thus the antioxidant capacity of the human epidermis is far
      greater than that of dermis. As the epidermis composes the outermost 10% of the
      skin and acts as the initial barrier to oxidant assault, it is perhaps not
      surprising that it has higher levels of antioxidants.

PMID- 8288905
TI  - Workshop on the pathogenesis of chronic wounds.

PMID- 8288906
TI  - Atopic dermatitis: recent trends in pathogenesis and therapy.
AB  - Emerging concepts in the areas related to the pathogenesis and treatment of
      atopic dermatitis are reviewed. In particular, recent findings have revealed
      several key steps in the maintenance of a vicious circle of spongiotic dermatitis
      associated with elevated T-lymphocyte activation, hyperstimulatory Langerhans
      cells, defective cell-mediated immunity, and B-cell IgE overproduction. The
      discovery of specific IgE-binding structures on Langerhans cells provides a
      mechanism for Langerhans cells to capture and present IgE-targeted allergens to
      allergen-specific T cells. Furthermore, certain microbial allergens that tend to
      preferentially elicit IgE-type responses also elicit a T-cell response dominated
      by the IgE-inducing lymphokine interleukin 4. Repeated stimulation by activated
      Langerhans cells appears to induce just such a response. Abnormal biochemical
      responsiveness and mediator release by AD monocytes, mast cells, and eosinophils
      also participate in the sustainment or initiation of such a vicious circle, and
      contribute directly to the dermatitis as well. Developments in the areas of
      neuropeptides, genetics, microbial superantigens, and cytokine networks in the
      skin also appear to have promise in providing a rational link between immune
      defects and the inflammatory events in AD. Conventional therapy remains the
      mainstay of atopic dermatitis management; however, new therapies based upon the
      above concepts are being tested in clinical trials. Although the difficulty of
      objectively grading AD lesional activity and the high placebo response of AD
      patients hampers the interpretation of many reports, several types of approaches
      are coming into focus. The effectiveness of cyclosporin A, which targets T-cell
      activation and antigen presentation, indicates that additional agents with such
      activity should be effective, and verifies the criticality of these cells in AD
      pathogenesis. Therapy with biologic response modifiers, such as interferon gamma
      or thymopentin, is oriented toward normalization of imbalanced immune
      responsiveness, rather than direct suppression of the immune system. The
      mechanism of action of and toxicities of Chinese herbal mixtures require further
      investigation, but may reveal hitherto unconsidered avenues. Other recent
      therapeutic trials have focused on reduction of trigger factors, such as house
      dust mite exposure, foods, and the abnormal epidermal lipid barrier to
      irritation.

PMID- 8288907
TI  - Green tea and skin--anticarcinogenic effects.
AB  - Because of its special aroma, green tea is a popular beverage consumed by some
      human populations worldwide. In recent years, many laboratory studies have shown
      that in a variety of animal tumor bioassay systems the administration of green
      tea, specifically the polyphenolic fraction isolated from green tea leaves (green
      tea polyphenols), affords protection against cancer induction. In mouse skin
      tumor bioassay systems, topical application of green tea polyphenols to skin has
      been shown to result in protection against a) 3-methylcholanthrene-induced skin
      tumorigenicity, b) 7,12-dimethylbenz(a)anthracene (DMBA)-induced skin tumor
      initiation, c) 12-O-tetradecanoylphorbol-13-acetate and other tumor promoters
      caused tumor promotion in DMBA-initiated skin, and d) benzoyl peroxide- and 4
      nitroquinoline N-oxide caused enhanced malignant progression of nonmalignant
      lesions. Green tea extract has also been shown to cause partial regression of
      established skin papillomas in mouse. Similarly, chronic oral feeding of green
      tea polyphenols or water extract of green tea has also been shown to result in
      the protection against both chemical carcinogen- and ultraviolet B radiation
      induced skin tumorigenicity. Collectively these data suggest that green tea
      possesses significant chemopreventive effect against each stage of
      carcinogenesis, and that it may be useful against inflammatory responses
      associated with the exposure of skin to chemical tumor promoters as well as to
      solar radiation. Available data regarding the mechanism by which green tea
      affords these diversified effects is discussed.

PMID- 8288908
TI  - Superantigenic staphylococcal exotoxins induce T-cell proliferation in the
      presence of Langerhans cells or class II-bearing keratinocytes and stimulate
      keratinocytes to produce T-cell-activating cytokines.
AB  - Several staphylococcal toxins are among a growing number of immunostimulatory
      molecules called "superantigens" because of their ability, when presented by
      appropriate major histocompatibility complex class II+ accessory cells, to
      activate essentially all T cells bearing particular T-cell receptor V beta gene
      segments. We have examined the ability of murine epidermal Langerhans cells
      and/or keratinocytes to act as accessory cells in the T-cell response to the
      superantigens staphylococcal enterotoxin B and exfoliative toxin, also known as
      epidermolysin. Purified murine splenic T cells were stimulated with
      staphylococcal enterotoxin B or exfoliative toxin in the presence of Langerhans
      cells--enriched epidermal cells from normal mice or epidermal cells isolated from
      mice pretreated with recombinant interferon-gamma, a procedure that induces the
      expression of major histocompatibility complex class II molecules on
      keratinocytes. The data show that both Langerhans cells and class II-bearing
      keratinocytes can act as accessory cells in the T-cell response to staphylococcal
      enterotoxin B and exfoliative toxin. We also observed that both human and murine
      keratinocytes cultured in the presence of staphylococcal enterotoxin B or
      exfoliative toxin produce increased amounts of cytokine(s) capable of stimulating
      thymocytes and D10 cells, and that this toxin activity is independent of the
      level of expression of class II on keratinocytes. Studies by enzyme-linked
      immunosorbent assay showed that staphylococcal enterotoxin B stimulates
      keratinocytes to produce tumor necrosis factor-alpha but not interleukin-1,
      suggesting tumor necrosis factor-alpha and perhaps other cytokines are
      responsible for the T-cell proliferative activity. These results demonstrate that
      two distinct epidermal constituents (i.e. Langerhans cells and keratinocytes) can
      serve as accessory cells in the responses of T cells to superantigenic bacterial
      toxins. It is possible that such toxins contribute to the pathogenesis of a
      variety of skin diseases by either locally activating T cells bearing particular
      V beta genes and/or enhancing keratinocyte production of immunomodulatory
      cytokines.

PMID- 8288909
TI  - Purification of the 230-kD bullous pemphigoid antigen (BP230) from bovine tongue
      mucosa: structural analyses and assessment of BP230 tissue distribution using a
      new monoclonal antibody.
AB  - In the epidermis the autoantigen BP230 is a component of the hemidesmosomal
      plaque. We have developed a procedure for the isolation of BP230 from bovine
      tongue mucosa using chromatographic means. The identity of the isolated protein
      was confirmed by its recognition by bullous pemphigoid autoantibodies. A
      monoclonal antibody (MoAb230), generated against the purified protein, localizes
      to the region of the plaque of the hemidesmosome with which keratin bundles
      interact. Furthermore, the tissue distribution of BP230, assessed using MoAb230,
      suggests that BP230 or an immunologically related protein is a component of all
      hemidesmosomes. Ultrastructural analyses of the BP230 preparation reveal that the
      BP230 molecules assemble into macromolecular aggregates. The few images of
      individual intact molecules that we have observed in platinum replicas of rotary
      shadowed BP230 preparations suggest that BP230 is an elongate rod-shaped
      molecule. This is consistent with predictions based on the primary sequence of
      BP230 deduced from BP230 cDNAs reported by others. We discuss our results in
      relation to the potential function of BP230. Isolation of BP230 should now allow
      more rigorous biochemical analyses of potential protein-protein interactions of
      BP230 in the hemidesmosome.

PMID- 8288910
TI  - Hypermutable ligation of plasmid DNA ends in cells from patients with Werner
      syndrome.
AB  - Werner Syndrome is a rare autosomal recessive disorder characterized by an
      increased cancer risk and by symptoms suggestive of premature aging. Cells from
      these patients demonstrate a typical pattern of chromosomal instability and a
      spontaneous hypermutability with a high rate of unusually large deletions. We
      have studied the in vivo DNA ligation in three lymphoblast cell lines from Werner
      syndrome patients and three from normal donors. In our host cell ligation assay
      we transfected linearized plasmid pZ189 and measured the amount of plasmid DNA
      ends rejoined by these host cells as the ability of the recovered plasmid to
      transform bacteria. A mutagenesis marker gene close to the ligation site allowed
      screening for mutations. Subsequent mutation analysis provided information about
      the accuracy of the ligation process. The cells from Werner syndrome patients
      were as effective as normal cells in ligating DNA ends. However, mutation
      analysis revealed that the three Werner syndrome cell lines introduced 2.4-4.6
      times more mutations (p < 0.001) than the normal cell lines during ligation of
      the DNA ends: the mutation rates were 69.4, 97.2, and 58.7%, as compared to 23.6,
      21.7, and 24.4% in the normal cell lines. These increased mutation frequencies in
      plasmids ligated during passage through Werner syndrome cells were mainly due to
      a significant (p < 0.001) increase in deletions. This error-prone DNA ligation
      might be responsible for the spontaneous hypermutability and the genomic
      instability in Werner syndrome cells and related to the apparently accelerated
      aging and high cancer risk in affected patients.

PMID- 8288911
TI  - Epidermis as a secretory tissue: an in vitro tissue model to study keratinocyte
      secretion.
AB  - In addition to protective functions, keratinocytes secrete a variety of effector
      molecules that may have local or distant effects. To explore the secretory
      activity of keratinocytes we have developed a two-chamber culture model in which
      a fully differentiated stratified epithelium is present in the upper chamber and
      secreted protein is collected in a lower chamber. A collagen matrix is not used
      and during collection of secreted protein, 3T3 feeder cells are absent.
      Keratinocytes secrete protein at the rate of 0.67 microgram/h/10(6) cells,
      encompassing a molecular weight range from several kD to over 180 kD. Secretion
      is an unexplored area of keratinocyte biology and this model will allow
      investigation of this activity.

PMID- 8288912
TI  - Secretion of apolipoprotein E by basal cells in cultures of epidermal
      keratinocytes.
AB  - Recently it has been shown that apolipoprotein E (apoE) secreted by keratinocytes
      in transplanted epidermal grafts reaches the systemic circulation. In this study
      we ask which cells in cultures of epidermal keratinocytes, basal or suprabasal,
      are the source of apoE. By fractionating disaggregated cultures in gradients of
      Ficoll400, the small nondifferentiated cells derived from the basal compartment
      were shown to be the source of apoE. The larger more differentiated cells derived
      from suprabasal layers could not be shown to contain or secrete apoE, although
      they did contain the apoE mRNA. Basal cells are the primary site for replication.
      However, analysis during growth in culture indicated that secretion did not
      correlate with cell replication but appeared to be linked to specific changes in
      metabolic activity of the basal cell compartment. Localization of apoE secretion
      to the basal compartment may provide a mechanism for lipid uptake and
      redistribution within the epidermis and may be viewed within the larger context
      of keratinocyte differentiation.

PMID- 8288913
TI  - Interleukin 1 alpha but not transforming growth factor beta inhibits tumor
      antigen presentation by epidermal antigen-presenting cells.
AB  - Cutaneous I-A+ Langerhans cells are the principal antigen-presenting cells within
      the epidermis, capable of both initiating and eliciting CD4-dependent immune
      reactions. We recently demonstrated that epidermal Langerhans cells can present
      tumor-associated antigens and thus may be important in cutaneous tumor immunity.
      Despite the ability of Langerhans cells to present tumor antigens, they generally
      fail to induce protective tumor immunity against growing tumors in situ. We
      therefore investigated whether locally produced cytokines may be able to down
      regulate the presentation of tumor-associated antigens and alloantigen by
      epidermal antigen-presenting cells in primed as well as in unprimed systems in
      vivo and in vitro. Naive syngeneic mice could be successfully immunized against
      the spindle cell tumor S1509a by injecting them with granulocyte-macrophage
      colony-stimulating factor-exposed and tumor-associated antigen-pulsed epidermal
      cells three times at weekly intervals. Co-incubation of epidermal cells in
      granulocyte-macrophage colony-stimulating factor and interleukin-1 alpha
      inhibited tumor-antigen presentation by epidermal antigen-presenting cells in
      this system and also inhibited alloantigen presentation in the primary mixed
      epidermal cell-lymphocyte reaction. Tumor necrosis factor-alpha appeared to be a
      significant mediator of the inhibitory effect of interleukin-1 alpha on the
      ability of epidermal antigen-presenting cells to induce protective tumor
      immunity, because addition of anti-tumor necrosis factor-alpha antibody abrogated
      the observed effect of interleukin-1 alpha. However, the effects of interleukin-1
      alpha and tumor necrosis factor-alpha differed with regard to presentation of
      tumor-associated antigens by epidermal antigen-presenting cells in a primed
      system. Whereas incubation of epidermal cells in interleukin-1 alpha before or
      after tumor antigen pulse inhibited their ability to elicit a delayed-type
      hypersensitivity response against S1509a tumor-associated antigens in tumor
      immune mice, culture in tumor necrosis factor-alpha significantly enhanced
      delayed-type hypersensitivity. Again, these in vivo data corresponded well to
      similar results obtained in vitro using the secondary mixed epidermal cell
      lymphocyte reaction. Incubation of epidermal cells in transforming growth factor
      beta, which has been shown to down-regulate T-cell-mediated immune responses in
      other systems, did not suppress tumor immunity in our assays. Thus, interleukin-1
      alpha may be an important regulator of Langerhans cell antigen-presenting
      function, having effects that are partially mediated via interleukin-1 alpha
      induced up-regulation of tumor necrosis factor-alpha secretion within the skin.

PMID- 8288914
TI  - Epidermis as a secretory tissue.

PMID- 8288915
TI  - Quantification of cellular proliferation in acne using the monoclonal antibody Ki
      67.
AB  - The mechanism by which ductal hypercornification occurs in acne is uncertain. We
      investigated proliferation in normal and acne follicles and in the
      interfollicular epidermis using the monoclonal antibody Ki-67, which reacts with
      a nuclear antigen expressed by cells in the G1, S, M, and G2 phases of the cell
      cycle. Cryostat sections of biopsies from the interscapular region from acne
      patients and from normal volunteers were stained with Ki-67 antibody and
      counterstained with 2% methyl green. The number of Ki-67-positive nuclei in the
      basal layer were counted and expressed as a percentage of the total number of
      basal nuclei in the ductal or interfollicular epithelia. The data was expressed
      as mean percent +/- SD. In normal follicles from acne-affected sites 17.40% +/-
      1.86% (n = 8) of the nuclei were Ki-67 positive. This was significantly higher (p
      < 0.01) than follicles from an area of skin unaffected by acne (11.01% +/- 6.16%,
      n = 8). In the follicular epithelia of non-inflamed lesions, the percentage of Ki
      67 positive nuclei was 23.44% +/- 8.36% (n = 15). It was impossible to count the
      nuclei of follicular epithelium of inflamed lesions because little of this
      remained intact. In normal interfollicular epidermis, Ki-67-positive nuclei
      represented 5.33% +/- 3.36% (n = 8) of the total. This value was not
      significantly different from the value obtained for interfollicular epidermis
      near non-inflamed lesions (10.46% +/- 4.45%, n = 15). However, the number of Ki
      67-positive nuclei in the interfollicular epidermis near inflamed lesions was
      significantly higher than either of these two values: 25.26% +/- 6.83%, n = 13, p
      < 0.05. Our results with Ki-67 confirm that ductal hyperproliferation occurs in
      acne and shows that normal follicles from acne skin may be "acne-prone."

PMID- 8288916
TI  - Office-based physician services provided by dermatologists in the United States
      in 1990.
AB  - Published epidemiologic data regarding dermatologic practice may no longer be
      current. The National Ambulatory Medical Care Survey conducted in 1990 provides a
      comprehensive assessment of ambulatory medical practice including patient
      demographics, chief and secondary complaints, diagnoses, and drug treatments
      prescribed. Many specialties including dermatology were represented in the
      sampling technique. The database was reviewed for descriptive aspects of visits
      to dermatologists surveyed. Using standardized weighting techniques, we estimated
      the total number of physician visits. Dermatologists had an estimated 24.0
      million patient encounters in 1990. Dermatologists treated a disproportionately
      large number of female and younger patients. After adjusting for their proportion
      of the population, Asians and Whites had greater numbers of dermatologic
      encounters than Blacks and Native Americans. Patients had two or more complaints
      27.2% of the time, and received two or more diagnoses 28.9% of the time. The most
      common complaints accounting for 49.7% of visits included "pimples," "rash,"
      "discoloration," "skin lesion," "wart," and "skin growth." The most common
      diagnoses, accounting for 52.7% of all encounters, were acne, keratosis, wart,
      dermatitis or eczema, benign neoplasm, and malignant neoplasm. This paper
      presents demographic information, chief and secondary complaints, and chief and
      secondary diagnoses of patients visiting dermatologists in the United States in
      1990. Whites and Asian or Pacific Islanders have increased utilization of
      services compared with Blacks and Native Americans or Eskimos; this disparity
      correlates with median family income.

PMID- 8288917
TI  - Interleukin-1 increases 15-hydroxyeicosatetraenoic acid production in human
      dermal fibroblasts.
AB  - Inhibition of the formation of pro-inflammatory eicosanoids such as leukotrienes
      and 12-hydroxyeicosatetraenoic acid by 15-hydroxyeicosatetraenoic acid (15-HETE)
      has been reported. Psoriatic dermis synthesizes reduced levels of 15-HETE and it
      has been postulated to play a role in the pathophysiology of this disease.
      Interleukin-1 stimulates the production of prostaglandin E2 in fibroblasts, but
      its effect on the synthesis of 15-HETE is at present unknown. The aim of this
      study was to investigate the modulation of 15-HETE formation by interleukin-1 in
      dermal fibroblasts. Cells were treated with recombinant interleukin-1 alpha or
      beta prior to incubation with exogenous 14C-arachidonic acid, and eicosanoids
      were analyzed by HPLC. Interleukin-1 significantly increased the production of 15
      HETE, but also 12-hydroxy-heptadecatrienoic acid, 11-hydroxyeicosatetraenoic
      acid, and prostaglandins, in a concentration- and time-dependent fashion. No
      significant differences between the two types of interleukin-1 were found.
      Dexamethasone (10 nM), and the protein synthesis inhibitors actinomycin D (1
      microM) and cycloheximide (3 micrograms/ml) completely abolished the effect of
      interleukin-1 on 15-HETE formation. Whereas indomethacin (0.5-25 microM) strongly
      inhibited the synthesis of 15-HETE, aspirin (100-1000 microM) was unable to
      significantly inhibit its formation in both untreated and interleukin-treated
      fibroblasts. Aspirin inhibited the 15-HETE produced by cyclooxygenase from ram
      seminal vesicles, although to a lesser extent than indomethacin. In cell-free
      extracts, the activity concerning the synthesis of 15-HETE was associated with
      the microsomal fraction (100,000 x g pellet). Overall, these results strongly
      suggest that interleukin-1 increases 15-HETE formation mainly through the
      expression of new cyclooxygenase.

PMID- 8288918
TI  - [Effect of dynamic cardiomyoplasty on the left ventricular function and
      hemodynamics in chronic canine models].
AB  - This study was undertaken to examine the effect of cardiac assist and left
      ventricular function after dynamic cardiomyoplasty (DCMP). In the first group
      (GI) of 10 mongrel dogs DCMP was drived immediately after wrapping both
      ventricles by latissmus dorsi muscle flap (LDMF). In the second group (GII) of 10
      mongrel dogs DCMP was derived over 6 weeks after production of DCMP for
      achievement of complete adhesion between LDMF and myocardium. In the both groups,
      aortic pressure, cardiac output, left ventricular systolic pressure, and ejection
      fraction of the left ventricle were significantly increased by DCMP driving (p <
      0.001). But left ventricular systolic pressure was remarkably increased in GII
      compared with that of GI (21.2 +/- 10.2% versus 14.0 +/- 9.6%, p < 0.001), and
      end diastolic pressure of the left ventricle was apparently decreased in GII
      (61.6 +/- 42.3% p < 0.05). Thus, satisfactory results were recognized that
      cardiac assist for left ventricular function was enhanced after completion of
      adhesion between myocardium and LDMF. Echocardiography in GII demonstrated that
      left ventricular systolic dimention was significantly decreased from 33.8 +/- 1.0
      mm to 27.6 +/- 1.2 mm (p < 0.001). Thus, left ventricular fractional shortening
      was significantly increased from 24.0 +/- 2.4% to 38.0 +/- 2.6% (p < 0.001).
      However, left ventricle end-diastolic dimention was not changed even during DCMP
      driving. So disturbance in left ventricular function during diastole could not be
      recognized. In conclusion, especially after adhesion of both muscles of LDMF and
      myocardium, effect of cardiac assist was remarkably enhanced, and disturbance of
      diastolic function of the left ventricle could not be observed.

PMID- 8288919
TI  - [Comparison between antegrade and retrograde cardioplegia with warm blood].
AB  - Recently continuous warm blood cardioplegia (BCP) has been reported as a superior
      method of myocardial protection, but it is unknown which is more effective
      antegrade or retrograde cardioplegia. This study was performed to investigate the
      efficacy of antegrade infusion via aortic root and retrograde infusion via
      coronary sinus with continuous warm BCP in regard to metabolism, oxygen
      extraction ratio, serum enzyme release, cardiac function, and myocardial edema.
      Fourteen adult mongrel dogs were subjected to total cardiopulmonary bypass and
      cross-clamp of the aorta for 120 minutes, and followed by 60 minutes reperfusion.
      The dogs were divided into two groups according to the infusion type of
      continuous warm blood cardioplegia: Group A, antegrade warm BCP, and Group R,
      retrograde warm BCP. Changes in excess lactate (delta XL), redox potential (delta
      Eh), and myocardial lactate extraction ratio showed that aerobic metabolism could
      be maintained in group A and could not in group R. Myocardial oxygen extraction
      ratio during aortic cross-clamp was same in group A and in group R, but at 5
      minutes after reperfusion it was significantly higher in group A than in group R
      (41 +/- 8% V.S. 22 +/- 9%). The incidence of ventricular fibrillation (V.F.)
      after reperfusion was significantly lower in group A than in group R (1/7 V.S.
      7/7). CPK-MB and HBDH releases during aortic cross-clamp and 60 minutes
      reperfusion were lower in group A than in group R, but not significant.
      Generations of lipid peroxides (A-Cs difference) were lower in group R than in
      group A, but not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288920
TI  - [Assessment of mechanical efficiency of coughing in pre- and post-operative lung
      cancer patients].
AB  - Mechanical efficiency of coughing (MEC) is assessed from the integral calculus of
      a square of expiratory flow rate divided with a square of tracheal transectinal
      area. Patients whose FEV1.0% was less than 60% had significantly low MEC,
      compared with patients whose FEV1.0% was more than 75%. esophageal pressure
      simultaneously measured at coughing was almost the same in both groups. Pre
      operative MEC was corrected in 82 lung cancer patients with the same manner as
      the prediction of expiratory flow rate after pulmonary resection. In 10 patients
      who needed bronchofiberscopic aspiration of sputum at post-operative days,
      corrected MEC was significantly lower than others who did not need it. MEC
      correlated closely with FEV1.0% divided with body surface area (correlation
      coefficient = 0.85). MEC was useful for assessment of post-operative difficulty
      of sputum drainage.

PMID- 8288921
TI  - [Anatomical study on the right bronchial artery for operation of esophageal
      cancer through right thoracotomy with special reference to the
      intercostobronchial arteries].
AB  - In view of the operative field of esophageal cancer, anatomical findings of the
      right bronchial arteries were studied in specimens of 71 cadavers.
      Intercostobronchial arteries were absent only in 3 cadavers (4.2%; group A). As
      22.6% of the cadavers had only one intercostobronchial artery supplied as the
      right bronchial artery (group B), it was considered to be important to preserve
      this artery. Cadavers both with the intercostobronchial artery and with the other
      right bronchial-arteries were observed in 70.4% (group C). Right bronchial
      arteries deriving from the aorta to course similarly to intercostobronchial
      arteries were present in small number (group D). Further, right bronchial
      arteries were classified into three types according to the deriving arteries as
      follows: (I) intercostobronchial arteries, (II) bronchial arteries deriving from
      the aorta, (III) other right bronchial arteries deriving from right subclavian
      artery, right inferior thyroid artery or right interthoracic artery. Considering
      difficulty of the approach from the operative field with right thoracotomy and
      the anatomical relationship with neighboring organs, it was thought that
      preserving the type (I) arteries is easy, the type (III) has a possibility to be
      preserved, and (II) is hard to be preserved. We concluded that preserving
      intercostobronchial arteries is important in esophageal cancer surgery approached
      through right thoracotomy because of small number of cadavers without these
      arteries and ease of preservation.

PMID- 8288922
TI  - [Comparison of various methods to close the stump of the main bronchus after
      pneumonectomy].
AB  - In 58 patients who underwent pneumonectomy, the stumps of the main bronchus were
      sutured manually (by the Sweet method in 13, the Overholt method in 12, and the
      modified Overholt method in 8) or with machines (TA-30 + S method in 15, TA-30 +
      O method in 10), and the methods to close the stump were evaluated according to
      the outcome and postoperative endoscopic findings. Cancer was positive at the
      stump in 3, and rupture of the membranous portion was observed in 1 in the
      mechanical suture group. Bronchial fistula was observed in 2 (12%) of the 25
      patients in the mechanical suture group but in none of the 33 patients in the
      manual suture group. The line of closure of the bronchial stump observed by
      endoscopy was perpendicular to the crest at the tracheal bifurcation in patients
      sutured by the Sweet or TA-30 + S method, angulated in a chevron shape in many of
      those sutured by the Overholt method and those sutured by TA-30 + O method, and
      parallel to the crest in part of those sutured by Overholt method and those
      sutured by modified Overholt method. The mucosa at the stump was uneven in many
      patients who showed chevron shaped closure lines. By the modified Overholt
      method, the wall of the main bronchus could be resected more extensively, the
      mucosa at the stump was smooth, and the airway lumen showed no marked
      deformation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288923
TI  - [Early and long-term results of sternocostal elevation combined with bridge
      external traction for funnel chest in children].
AB  - The purpose of the present study is to evaluate the effects of addition of a
      bridge external traction to our conventional sternocostal elevation technique in
      the surgical management of funnel chest in children. During the period from 1970
      to 1979, a total of 29 children with funnel chest were treated surgically using
      sternocostal elevation technique (Group I). Operative technique consisted of
      total subperichondral resection of deformed costal cartilages (usually 3rd to
      8th, bilaterally), transection of deformed portion of the sternum in 2-3 points
      and fixation of the sternum in elevated position using 2 Kirschner wires, and
      shortening resuturing of the opened perichondrium. Since 1980, an addition of the
      bridge external traction to our conventional sternocostal elevation technique was
      applied for about 10 days after operation in 82 consecutive children (Group II).
      The vertebral index (B/A = sagittal diameter of vertebral body/minimum
      sternovertebral distance), D/C ratio (maximum sagittal depth of depression of
      sternum/distance from anterior surface of the vertebral body to the sternum at
      Louis's angle) and E/C ratio (E = minimal sagittal distance from anterior surface
      of the vertebral body to the sternum) were measured in all cases and compared
      before and after operation and also between the two Groups. Preoperatively, there
      was no significant difference in all 3 indices between the two Groups.
      Postoperative B/A, D/C and E/C ratio in Group I were 0.28 +/- 0.06, 0.14 +/-
      0.19, 1.09 +/- 0.32 (mean +/- SD), respectively. There were a significant drop in
      D/C ratio and a significant elevation in E/C ratio after operation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8288924
TI  - [External work of canine latissimus dorsi muscle after vascular delay].
AB  - The first purpose of this study was to estimate physiological performance of
      skeletal muscle for circulatory assist. External work in the form of linear
      dynamic contraction was studied in canine latissimus dorsi muscle (LDM). The
      second purpose was to relate the effect of vascular delay of the LDM to the
      physiological performance. The left LDM with vascular delay (VD) were compared to
      the right control LDM (CTR) without vascular delay. Simultaneous dynamic
      contraction of both VD and CTR LDM were studied under various settings of the
      preloads and the afterloads. Maximal external work per single contraction were
      136 +/- 38 mJ in VD and 81 +/- 21 mJ in CTR. Maximal total work, which includes
      external work and preload work, were 578 +/- 195 mJ in VD and 407 +/- 146 mJ in
      CTR. Maximal fractional shortenings of the LDMs were 22.8 +/- 4.7% in VD and 17.5
      +/- 2.6% in CTR. The maximal external work of VD was 81% of canine LV stroke work
      and 620% of canine RV stroke work. The maximal total work of VD was 340% of
      canine LV stroke work. The fractional shortenings, external work and total work
      of VD were higher than those of CTR under all loading conditions. The physiologic
      performance of canine LDM was improved after vascular delay.

PMID- 8288925
TI  - [Effect of dynamic cardiomyoplasty on coronary arterial blood flow].
AB  - We investigated whether or not dynamic cardiomyoplasty adversely affected
      coronary arterial blood flow (CABF) through compression of the coronary arteries
      by muscular contraction during systole and incomplete relaxation of the skeletal
      muscle flap during diastole. Dynamic cardiomyoplasty was performed in 20 mongrel
      dogs using a left latissimus dorsi muscle flap, paced synchronously with the R
      wave of the electrocardiogram. A Doppler catheter (3 F in diameter) was placed in
      the left main trunk of the coronary artery to analyze the instantaneous changes
      of coronary arterial blood flow velocity by fast Fourier transformation analysis.
      We compared both systolic and diastolic properties during assisted versus
      unassisted cardiac cycles by calculating the peak velocity and the time velocity
      integrate (TVI). A significant enhancement of systolic CABF was recognized by
      increases in the systolic peak velocity (26.5 +/- 29.2%) and TVI (20.2 +/-
      38.6%). The improved systolic CABF was consistent with an increase in systolic
      aortic pressure (15.5 +/- 4.3%) and stroke volume (42.8 +/- 11.2%). CABF was also
      enhanced in diastole because a significant increase of diastolic peak velocity
      (4.4 +/- 9.4%) and TVI (11.0 +/- 16.7%) was observed. Enhancement of diastolic
      CABF was associated with the augmentation of cardiac function and the reduction
      of left ventricular end-diastolic pressure. It could be concluded that CABF was
      increased by the enhancement of cardiac function as a result of dynamic
      cardiomyoplasty leading to an increase of cardiac output and aortic pressure and
      a decrease of left ventricular end-diastolic pressure.

PMID- 8288926
TI  - [The effectiveness of ulinastatin on granulocyte H2O2 production in acute lung
      injury rat model].
AB  - Oxygen radicals produced by granulocytes play an important role in acute lung
      injury. The effectiveness of ulinastatin in adult respiratory distress syndrome
      and an acute lung injury animal model has been reported. We investigated the
      effect of ulinastatin on oxygen radical production in the intact pulmonary
      circulation of a rat acute lung injury model using our new method, which
      demonstrated the granulocyte adhesion and H2O2 production in vivo. The pulmonary
      microcirculation was observed by intravital fluorescence microscopy and a TV
      monitor using a SIT TV camera. Then images were recorded on a videotape. The
      granulocytes and H2O2 were stained with an intravenous injection of acridine red
      and dichlorofluorescin diacetate, respectively. The images which were recorded on
      the videotape were digitized by a computer image digitizer and analyzed with a
      personal computer and the software Ripp II. When the rat received a continuous
      infusion of endotoxin (4.5 mg/kg/hour) for 2 hours, the granulocytes adhered to
      the pulmonary capillaries and generated H2O2 (n = 25 p < 0.001 respectively,
      compared with the control rat which received saline alone). Then, the acute lung
      injury model rat was infused with 50,000 U/kg of ulinastatin just before
      endotoxin infusion and also received a continuous infusion of ulinastatin (50,000
      U/kg/hour) for 2 hours. Ulinastatin inhibited the granulocyte adhesion to the
      pulmonary capillaries (n = 25, inhibition rate: 46% p < 0.001) and H2O2
      production (n = 25, inhibition rate; 51% p < 0.001) caused by the continuous
      infusion of endotoxin. In conclusion, ulinastatin significantly inhibits the
      granulocyte adhesion and H2O2 production in the intact pulmonary circulation of a
      rat acute lung injury model.

PMID- 8288927
TI  - [Response to exercise in patients after repair of tetralogy of Fallot].
AB  - Cardiac catheterization and submaximal exercise testing was performed in 38
      patients after repair of tetralogy of Fallot (TF), and compared to 6 control
      patients who had functional murmurs. Cardiac index, heart rate, and stroke volume
      index were significantly lower in the TF group than in the control group. Right
      and left ventricular end-diastolic pressure increased significantly during
      exercise, which was not found in the control group. Total pulmonary vascular
      resistance (TPVR), which decreased significantly with exercise in the control
      group, did not change remarkably during exercise. TPVR was significantly higher
      in the TF group than in the control group both at rest and during exercise.
      Several factors were compared between patients with good cardiac index (> 5.0
      l/min/m2; Group 1) and poor cardiac index (< 5.0 l/min/m2; Group 2) during
      exercise. Stroke volume index, right ventricular ejection fraction at rest were
      significantly higher in Group 1 than Group 2. TPVR, right and left ventricular
      end-diastolic and end-systolic volume index were significantly lower in Group 1
      than in Group 2. There was no significant difference in heart rate, left
      ventricular ejection fraction, residual pulmonary stenosis, right to left
      ventricular systolic pressure ratio, and severity of pulmonary regurgitation
      between two groups. These findings indicate that abnormalities of exercise
      tolerance in patients after repair of TF were related to poor response of heart
      rate, pulmonary vascular resistance, and systolic and diastolic ventricular
      function.

PMID- 8288928
TI  - [Coronary revascularization using profound hypothermia with elective ventricular
      fibrillation and total circulatory arrest].
AB  - Profound hypothermia with elective ventricular fibrillation and total circulatory
      arrest was used in a patient undergoing coronary artery bypass grafting (CABG)
      with severe calcification of the ascending aorta. A 76-year-old woman with
      unstable angina was referred for coronary revascularization. Ascending aorta was
      severely calcified with the exception of limited region of proximal ascending
      aorta, and the coronary arteriography showed high-grade obstruction of the left
      anterior descending (LAD) and dominant right coronary artery (RCA). The left
      internal thoracic artery was anastomosed to the LAD, and the saphenous vein graft
      to the RCA under systemic moderate hypothermia and elective ventricular
      fibrillation. During the proximal anastomosis of the saphenous vein graft to the
      non-calcified ascending aorta, profound hypothermia and circulatory arrest was
      instituted for 11 minutes. The wean from extracorporeal circulation was
      successful, and the postoperative course was uneventful.

PMID- 8288929
TI  - [Traumatic tricuspid regurgitation--report of two cases and review of operated
      cases].
AB  - Two cases of nonpenetrating traumatic tricuspid regurgitation were reported. The
      first case, a 46-year-old man who had an episode of traffic accident 21 years
      ago, was admitted with complaints of peripheral edema and dyspnea on exertion.
      The second case was a 16-year-old man who noted to have cardiac murmur and
      cardiomegaly after 4 years of a traffic accident. In both cases, cardiac
      catheterization showed increased right atrial pressure with high v wave, and
      echocardiogram showed severe tricuspid regurgitation with ruptured chordae
      tendineae of the anterior leaflet. Tricuspid valve replacement was performed
      successfully in both the cases. Twenty-two operated cases of traumatic tricuspid
      regurgitation have been reported in Japan; 17 of ruptured chordae tendineae, 3 of
      ruptured papillary muscle, and 2 of primary laceration of anterior leaflet. The
      patients with ruptured papillary muscle were operated from 2 months to 7 years
      (average 4 years) after trauma, while those with ruptured chordae tendineae were
      operated from 5 months to 25 years (average 10 years) after trauma. Tricuspid
      valve replacement was performed in 17 of 22 cases. From the review of 22 cases,
      tricuspid valve replacement should be indicated for traumatic tricuspid
      regurgitation in consideration of the severity of valve destruction regardless of
      the interval after trauma.

PMID- 8288930
TI  - [Two cases of thymic cysts and review of the 220 Japanese cases].
AB  - Thymic cyst is relatively rare disease among mediastinal tumors. We reported two
      cases of surgical resected thymic cysts. Case 1: A 72-year-old female was found
      to have an abnormal shadow at right cardio-phrenic angle on chest X-ray film.
      Operative and pathological diagnosis was thymic cyst. Immunohistochemical study
      showed the epithelial cells lining the cyst to contain keratin and CEA but not
      CA19-9. Case 2: A 67-year-old male was pointed out to have an abnormal shadow at
      left mediastinum on a chest X-ray film during his stay in our hospital for acute
      myocardial infarction. Preoperative diagnosis was made to be a thymic cyst and
      operation was done. Pathological diagnosis was the same. Behcet's disease was
      accompanied in this patient. It is very rare to be complicated with thymic cyst.
      We reviewed 220 operated cases of thymic cyst in the Japanese literature.

PMID- 8288931
TI  - [Successful surgical management of postinfarction left ventricular free wall
      rupture in a case of systemic lupus erythematosus].
AB  - A 58-year-old woman of postinfarction left ventricular free wall rupture (LVFWR)
      was surgically treated with good results. She had been treated with Prednisolon
      for 15 years with the diagnosis of systemic lupus erythematosus. The rupture was
      noted six hours after the onset of myocardial infarction and she was taken to the
      emergent surgical intervention. During the operation, active bleeding was found
      in the higher anterior wall of the left ventricle and a Dacron graft was sutured
      to cover the infarcted area. The postoperative course was uneventful. This report
      seemed to be the first one of the successful surgical management of LVFWR in the
      course of the treatment for SLE in the literature.

PMID- 8288932
TI  - [A case of modified maze operation for atrial fibrillation accompanied by mitral
      stenosis].
AB  - A 45-year-old man suffering from mitral stenosis and atrial fibrillation
      underwent a mitral commissurotomy and received a modified maze operation. In
      order to preserve the sinus node artery, we used a new incision line differing
      from that of Cox and introduced a cryosurgery. After the operation, atrial
      fibrillation disappeared. The atrial kick was also clearly observed by the
      echocardiogram. We think that combined operations have advantage both to cure
      atrial fibrillation and to deal with the mitral valve easily.

PMID- 8288933
TI  - [A successful case report of coronary bypass grafting by utilizing inferior
      epigastric artery, gastroepiploic artery and bilateral internal thoracic artery].
AB  - We performed coronary artery bypass grafting with the bilateral internal thoracic
      artery (ITA), right gastroepiploic artery (RGEA) and inferior epigastric artery
      (IEA) on a 53-year-old patient who was associated with familiar
      hypercholesterolemia. The IEA was extended with right ITA as a composite graft
      and sequentially anastomosed to the right coronary artery and distal branch of
      the right coronary artery. Both the LITA to the left anterior descending artery
      and the RGEA to the circumflex artery were used as in situ graft. The
      postoperative coronary angiogram showed all the graft patient.

PMID- 8288934
TI  - [Clinical study of 8 cases of spontaneous esophageal rupture].
AB  - Among 8 patients with spontaneous esophageal rupture, mean age was 46.5 years,
      and there was only one female. Vomiting after drinking was the main cause of
      onset. In 4 patients who underwent drainage of the thoracic cavity or initial
      treatment by surgery within 24 hrs after onset, closure after layer-layer suture
      of the site of rupture was made in two patients in whom definitive diagnosis was
      obtained at the first medical examination and early discharge was possible. A
      definitive diagnosis was obtained after drainage of the thoracic cavity in the
      other two patients, and esophagectomy without thoracotomy was performed on the
      55th day after onset in one and the other patient received only conservative
      treatment without surgery, both patients were discharged. Of 4 patients who
      underwent treatment after 24 hrs, two patients who recovered included one who
      received only conservative treatment and another who underwent closure by suture
      of the site of rupture and covering with a pedicled omental flap 12 days after
      onset. The other two patients died of MOF after operation. We propose the
      following guidelines for treatment of this condition; In patients in whom
      surgical treatment is possible within 24 hrs after onset, closure by layer-layer
      suture of the site of rupture may be indicated. In cases in which more than 24
      hrs has elapsed after rupture spontaneous closure sometimes can be expected in
      patients with a rupture would less than 2 cm. In patients accompanied with
      progressing mediastinitis or pyothorax with drainage procedure surgical treatment
      is indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288935
TI  - [TV-assisted thoracoscopic surgery with a lung forceps combined with thoracoscope
      under local anesthesia for spontaneous pneumothorax with a persistent air leak--a
      single access port approach].
AB  - TV-assisted thoracoscopic surgery was performed under local anesthesia by through
      a single access port to control a continuing air leak in spontaneous pneumotorax.
      A 75-year-old man was admitted with severe dyspnea and right-sided chest pain.
      The chest X-ray film showed right lung collapse. A right spontaneous pneumothorax
      was diagnosed and was treated by chest tube drainage. However, the lung did not
      re-expand because of a continuing air leak and subcutaneous emphysema developed.
      TV-assisted thoracoscopic surgery was performed under local anesthesia to treat
      the persistent air leak on day 12. By endoscopy, the ruptured bulla was double
      ligated with an Endoloop through a single access port using lung forceps combined
      with endoscope. The air leak subsequently ceased and the lung re-expanded. This
      method is minimally invasive and is very suitable for controlling a continuing
      air-leak causing spontaneous pneumothorax in a patient.

PMID- 8288936
TI  - [A case of subtotal esophagectomy for esophageal basaloid carcinoma after mitral
      valve replacement].
AB  - We reported a rare case of subtotal esophagectomy for esophageal basaloid
      carcinoma after mitral valve replacement. Up to present, only this case had been
      printed in Japan. A 51-year-old male who had been performed MVR for mitral
      stenosis at the 44 complained of dysphagia. On esophageal X-ray and
      esophagoscopic findings showed round, irregular, and stenotic lesion (type-3) in
      the middle thoracic esophagus. We performed subtotal esophagectomy,
      esophagogastrostomy through the posterior mediastinal pathway and lymph node
      dissection (R2). Despite normal cardiac function before operation, the patient
      followed lung edema and perioperative measurement of Extra Vascular Lung Water
      Index (EVLWI) was stable within high level. On microscopic inspection, we
      revealed lots of basophilic basal cells mainly occupied submucosal layer
      coexisted with pseudoglandular formation and poorly differentiated squamous cell
      carcinoma. And the tumor cells strongly invaded into the lymph ducts and blood
      vessels. We need more detailed exploration for more cases about factors causing
      poor prognosis.

PMID- 8288937
TI  - [Successful treatment of fungal endocarditis and mediastinitis after fenestrated
      Fontan operation--a case report].
AB  - Fenestrated Fontan operation was performed in a 19-year-old male with a diagnosis
      of right isomerism syndrome. Postoperatively, fungal endocarditis due to Candida
      Albicans and mediastinitis by Methicilin resistant Staphylococcus Aureus (MRSA)
      occurred. For Candida endocarditis, combined surgery and medical treatment with
      amphotericin B was effective. MRSA mediastinitis was successfully treated by
      continuous closed irrigation with 0.5% povidone-iodine solution. This is the 17th
      reported case of fungal endocarditis after open heart surgery in Japanese
      literature.

PMID- 8288938
TI  - [An adult case of left ventricular-right atrial communication with a false
      aneurysm of membranous septum].
AB  - A case of left ventricular-right atrial (LV-RA) communication associated with a
      false aneurysm of membranous septum is presented. The patient was a 51-year-old
      woman. Using a left ventriculography this case was diagnosed preoperatively as LV
      RA communication. We found that the right atrium was directly communicated with
      the left ventricle through a fibrous membranous aneurysm adhering to the septal
      leaflet of the tricuspid valve. It was suggested that a false aneurysm, made by
      jet lesion from the left ventricle, perforated to the right atrium. So the
      current case was considered an acquired infravaluvular type LV-RA communication
      formed in the course of the natural closure of the membranous ventricular septal
      defect.

PMID- 8288939
TI  - [Aortic valve re-replacement with a SJM valve by aortic ring re-enlargement with
      Nick's method--report of a successful case].
AB  - An 11-year-old girl had undergone an aortic valve replacement for congenital
      aortic stenosis with #17 Bjork-Shiley valve and aortic ring enlargement by Nick's
      method eight years later, the pressure gradient across the prosthetic valve
      increased up to 100 mmHg. Re-aortic valve replacement was successfully performed
      with #21 St. Jude Medical valve, when aortic valve ring increased to accommodate
      #21 SJM valve.

PMID- 8288940
TI  - [A coronary aneurysm of left main trunk associated with localized dissecting
      aneurysms of thoracic and abdominal aorta].
AB  - A 47-year-old man who had undergone surgery of a dissecting thoracic aortic
      aneurysm was admitted for a localized, dissecting abdominal aortic aneurysm.
      Preoperative coronary arteriogram incidentally showed a coronary artery aneurysm
      (CAA) of the left main trunk. Prior to the operation for abdominal aortic
      aneurysm, that for the CAA was performed under standard cardiopulmonary bypass
      conditions with antegrade and retrograde coronary sinus cold blood cardioplegia.
      A longitudinal incision of the aneurysmal wall was made for the removal of a
      small thrombus and, the ostia of the left anterior descending artery (LAD),
      circumflex artery (LCX), intermediate artery (IM) and main trunk were closed from
      the inside of the aneurysm. The aneurysmal wall was closed without resection of
      the whole aneurysm. Finally, coronary artery bypass grafting to LAD, LCX and IM
      was performed. Postoperative course was uneventful with patency of all grafts.
      The retrograde coronary sinus cardioplagia is effective to prevent
      thromboembolism of distal coronary arteries due to the antegrade cardioplagia.

PMID- 8288941
TI  - [A case of mitral valve re-replacement with radical correction of Bland-White
      Garland syndrome].
AB  - A case of an 8-year-old girl with Bland-White-Garland syndrome (BWG) who
      successfully underwent a second mitral valve replacement is reported. The patient
      had a past history of mitral valve replacement under the diagnosis of mitral
      regurgitation and pulmonary hypertension at one year and 3 months of age. Cardiac
      catheterization at 6 years and 3 months of age revealed an anomalous origin of
      the left coronary artery from the pulmonary artery but she was asymptomatic. One
      year and 7 months later, she was admitted to our institution with a sudden onset
      of chest pain and respiratory distress. Right heart pressure study using a Swan
      Ganz catheter showed severe pulmonary hypertension and elevated mean pulmonary
      wedge pressure (38 mmHg). Echocardiogram revealed severe mitral stenosis and
      moderate regurgitation. She was diagnosed under fluoroscopy as acute left cardiac
      failure due to stuck valve and suspected having myocardial damage due to BWG,
      thus, emergency surgery was performed. Under cardiopulmonary bypass, aorto-left
      coronary arterial continuity was established by intrapulmonary arterial tunnel
      using Hamilton's technique. After resection of the prosthetic valve, of which one
      of two leaflets had been fixed in pannus, re-MVR was done with a St. Jude.
      Medical valve (25 mm). Postoperative angiogram demonstrated satisfactorily
      reconstructed two coronary artery systems. Postoperatively, she has been doing
      well without complaint for the last eighteen months.

PMID- 8288942
TI  - [Viability of cryopreserved heart valve].

PMID- 8288944
TI  - Properdin: approaching four decades of research.
AB  - Properdin plays a key role in the alternative pathway by stabilizing the C3
      convertase. This review chronicles the evolution of our knowledge of the
      structure and function of properdin over the 40 years since its discovery. The
      story begins with the first description of properdin and the controversy that
      ensued over its existence. Then, this review describes: the rediscovery and
      acceptance of properdin and the alternative pathway as important components of
      natural immunity; properdin structure and molecular sequence; speculations on the
      significance of sequence similarities to thrombospondin and other proteins, and
      properdin biosynthesis. Finally, this review characterizes properdin deficiency.
      Properdin does indeed appear to play an important role in homeostasis.

PMID- 8288943
TI  - Complement biosynthesis by mononuclear phagocytes.
AB  - Mononuclear phagocytes are an important in vivo source of a wide range of
      complement components. They are able to rapidly up-regulate or down-regulate
      complement synthesis in response to many different pharmacological and biological
      stimuli. This ability is likely to make a significant contribution to maintaining
      host defences particularly in peripheral tissues. The important role of molecular
      biology in the study of complement biosynthesis by mononuclear phagocytes will be
      emphasised.

PMID- 8288945
TI  - Membrane signaling by complement C5b-9, the membrane attack complex.
AB  - The terminal complement complexes C5b-7, C5b-8 and C5b-9 are able to generate
      nonlethal cell signals. One universal consequence of a cell being targeted by C5b
      8 or C5b-9 is an influx of Ca2+. In addition, other second messengers, including
      cAMP, inositol phosphate intermediates and arachidonate metabolites, are
      generated by the terminal complement complexes in specific cell types. In vivo,
      terminal complement complexes have been found in a wide variety of inflammatory
      processes in humans and in experimental animal models. Some of these models of
      inflammation putatively induced by terminal complement complexes have been tested
      in complement-deficient animals, and indeed no inflammation results, which
      supports the critical role of the terminal complement complexes in the
      pathogenesis of the lesion.

PMID- 8288947
TI  - Complement deficiency states and meningococcal disease.
AB  - Analysis of complement deficiency states has supported the role of complement in
      host defense and elucidated diseases associated with defective complement
      function. Although neisserial infection plays a prominent role in these
      deficiency states, examination of individuals with late complement component
      deficiency (LCCD) reveals a particular propensity for recurrent meningococcal
      disease and provides important clues to the role of complement in neisserial
      infections. In response to meningococcal disease, LCCD individuals produce
      significantly greater amounts of antilipooligosaccharide (LOS) antibody which can
      kill group B meningococcus in a complement-sufficient in vitro system. Further
      studies of antibody cross-reactivity to other meningococci has led to a clearer
      understanding of its epitopic specificity. Nevertheless, epidemiologic evidence
      is consistent with the relative absence of protective immunity in LCCD persons
      following an episode of infection and supported by quantitation of antibody to
      capsular polysaccharide. However, compared to anti-LOS antibodies, anticapsular
      antibodies can offer immune protection to LCCD individuals via complement
      dependent opsonophagocytosis--the only form of complement-mediated killing
      available to these persons. Thus vaccination of LCCD persons with capsular
      antigens is considered an important means of protecting these high-risk
      individuals against meningococcal disease.

PMID- 8288948
TI  - The complement system and systemic sclerosis.
AB  - Serum concentrations of the various complement components including the classical
      and the alternative pathways were determined in 58 control healthy subjects and
      80 patients with systemic sclerosis (SSC). The mean concentrations of C1q, C2,
      C5, C6, C7, C9, and factor B were significantly increased in the SSC patients in
      comparison to controls, while the increases were not significant for C3 and C8.
      C4 was an exception in that the mean levels were found to be decreased, with 18
      patients having levels < 65% of the mean normal value. Properdin was also found
      to be decreased, but not significantly. We found a similarity between the pattern
      of serum complement component concentrations in SSC patients and patients with
      primary biliary cirrhosis, two disorders frequently associated in the same
      patients. The significance of complement component patterns in these diseases is
      discussed.

PMID- 8288946
TI  - Complement in human reproduction: activation and control.
AB  - The behaviour of the complement system during human reproduction is now the focus
      of much scientific attention. The presence of antisperm antibodies in the
      reproductive tracts of some infertile individuals, and of complement in cervical
      and ovarian follicular fluid, suggests that complement-mediated damage of
      spermatozoa is involved in some cases of infertility. Further, deposition of
      maternal IgG and of complement in the extrafetal tissues indicates that
      complement activation occurs within the fetoplacental unit. Recently, three
      complement-regulatory proteins--decay-accelerating factor, membrane cofactor
      protein and CD59--have been detected on spermatozoa and in the extrafetal
      tissues. It is likely that these inhibitors are essential for normal reproductive
      function. This article reviews current understanding of the interaction of the
      complement system with cells and tissues involved in reproduction, with emphasis
      on the nature and function of the controlling proteins.

PMID- 8288949
TI  - Zinc ions potentiate adenosine diphosphate-induced platelet aggregation by
      activation of protein kinase C.
AB  - Zinc deficiency has been linked to a bleeding tendency and impaired wound healing
      in several disease states. A number of investigators have suggested that zinc
      ions play a role in platelet aggregation in vitro as well as in in vivo studies.
      The purpose of the present study was to explore the mechanism by which adenosine
      diphosphate (ADP) and Zn2+ may act cooperatively during activation of blood
      platelets. We demonstrate that Zn2+ alone does not affect either formation of
      thromboxane A2 or intracellular calcium mobilization in platelets. On the other
      hand, we show that ADP and Zn2+ exert a cooperative effect on the phosphorylation
      of P-47 protein (pleckstrin), a substrate of protein kinase C in platelets. The
      inhibitory effect of this reaction by the compound Ro31, a specific inhibitor of
      the regulatory domain of protein kinase C, was compatible with our contention
      that Zn2+ may act directly on protein kinase C. Our study provides evidence that
      zinc ions present in plasma or platelets may modulate ADP-induced platelet
      aggregation. N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a zinc
      chelator, blocked ADP-induced platelet aggregation. This aggregation was restored
      by 10 mumol/L of Zn2+ but not by other ions. Also, a Zn2+ ionophore, pyrithione,
      potentiated the ADP-induced platelet aggregation and this potentiation was
      blocked by TPEN. Experiments with the zinc ionophore suggest that intracellular
      zinc ions play an important role in activation of platelets, and in the absence
      of other platelet agonists it appears that it may be a requirement for ADP
      induced platelet aggregation to occur.

PMID- 8288950
TI  - Accelerated gastric emptying in diabetic rodents: effect of insulin treatment and
      pancreas transplantation.
AB  - Gastric emptying of a suspended solid, digestible meal was examined after 30 to
      90 days of diabetes in two strains of streptozotocin-treated rodents and in
      genetically diabetic BB/Wor rats. After a 14-hour overnight fast the animals were
      gavage-fed 1.0 gm of rat food suspended in water and were killed 30 minutes
      later. Ligatures were placed around the lower esophageal sphincter and the
      pylorus and the stomachs were removed intact. The stomachs were evacuated and the
      gastric contents and gastric remnant were separately dried and weighted. Both the
      streptozotocin-treated and BB/Wor rats showed significantly accelerated (1.5- to
      2.2-fold) rates of gastric emptying of the meal compared with respective
      nondiabetic control animals. Streptozotocin-treated diabetic animals that
      received daily insulin supplementation or those that had undergone pancreas
      transplantation shortly after induction of diabetes showed a similar reduction in
      blood glucose levels and normal rates of gastric emptying. Diabetes had a
      significant but variable effect on gastric mass and body weight. This response
      was dependent on the strain of animal examined, whether or not insulin
      supplementation was administered, or whether the animal underwent pancreas
      transplantation. These observations indicate that early diabetes in rodents has a
      prokinetic effect on gastric emptying of a suspended solid digestible meal.
      Restoration of euglycemia by insulin treatment or pancreas transplantation is
      associated with return of the gastric emptying rate to normal. These changes in
      gastric emptying appear to be independent of the effects of diabetes on gastric
      mass.

PMID- 8288951
TI  - The effect of prednisolone and a protein-deficient diet on plasma albumin and
      fibrinogen in a turpentine-induced acute-phase reaction in rats.
AB  - The acute-phase reaction (APR) that follows inflammation is characterized by
      profound metabolic changes such as hypoalbuminemia, which is frequently
      aggravated by malnutrition; and hyperfibrinogenemia. Because some of these
      changes are mediated by cytokines, corticosteroids that are known to suppress
      cytokine production might be expected to alleviate the course of the APR. In the
      present study, for 3 weeks rats were fed (1) a standard diet (25%) protein), (2)
      a protein-deficient diet (5% protein), or (3) a standard diet supplemented by
      treatment with intraperitoneal prednisolone (7.5 mg twice daily starting 3 days
      before and throughout the experiment). Changes in plasma albumin, fibrinogen, and
      total protein levels were measured 0, 1, 3, and 8 days after turpentine was
      injected subcutaneously. Albumin and fibrinogen were immunohistochemically
      stained in the liver 0, 3, and 8 days after injection. Plasma albumin decreased
      by roughly 50% in all three groups, and reached a nadir on day 3. Fibrinogen
      peaked by day 1 in all animals and fell gradually thereafter. The total protein
      concentration, which was higher with prednisolone, remained unchanged in all
      three groups. The level of immunostainable liver albumin was initially reduced in
      malnourished rats. If further diminished in the majority of hepatocytes after
      administration of turpentine in all groups. Although few hepatocytes stained
      positive for fibrinogen before the onset of inflammation, uniform increase in
      immunostaining occurred by day 3 in all rats regardless of treatment. Neither
      prednisolone nor malnutrition substantially altered the decrease in plasma
      albumin and the simultaneous increase in fibrinogen in a turpentine-induced
      APR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288952
TI  - Antimalarial quinones: redox potential dependence of methemoglobin formation and
      heme release in erythrocytes.
AB  - A number of quinones have been shown to be effective antimalarials. In addition
      some have been shown to have oxidant effects on glucose-6-phosphate dehydrogenase
      deficient red cells. To clarify the mechanism of this oxidant effect and to
      determine whether it is a general property of antimalarial quinones, the effects
      of five compounds on red cells were studied. Two, 5-hydroxy-6-demethyl pentaquine
      (5H6DP) and menadione, caused marked methemoglobin production and the insertion
      of heme into the red-cell membrane. The other three, atovaquone, daphnetin, and
      menoctone, did not. The insertion of heme into membranes caused diminished
      deformability, and this might account for the hemolytic effects. Redox potentials
      of all five compounds were measured. The two quinones that caused heme release,
      menadione and 5H6DP, had redox potentials of -141 +/- 12 and -97 +/- 25 mV,
      respectively, which are similar to the reported redox potentials for hemoglobin.
      The other three quinones had redox potentials that were either significantly
      higher or lower. Thus only quinones of the appropriate redox potentials are
      likely to be toxic to red cells.

PMID- 8288953
TI  - Enhanced production of oxygen radicals in asthma.
AB  - Oxygen radicals have been implicated in a variety of disease processes including
      asthma. In this study we investigated the production of superoxide by airspace
      cells in 56 patients with asthma as compared with 49 normal controls. We found
      that with patients with asthma with a forced expiratory vital capacity in the 1st
      second (FEV1) of less than 80% (n = 13) had higher spontaneous superoxide (SO)
      production when compared with normal subjects (3.6 +/- 1.0 versus 1.9 +/- 0.2
      nmol/5 x 10(5) cells/hour, p < 0.01), whereas those with FEV1 > 80% (n = 40) were
      similar to normal subjects in superoxide generation (2.1 +/- 0.3 nmol/5 x 10(5)
      cells/hour). Airspace cells from patients with mild asthma and those with
      moderate asthma had higher phorbol myristate acetate (PMA)-stimulated SO
      production when compared with those from normal subjects (8.9 +/- 0.7, 11.1 +/-
      2.4, and 6.5 +/- 0.4 nmol/5 x 10(5) cells/hour respectively, p < 0.005, r = 
      0.35, both comparisons). However, PMA-stimulated SO production was similar in
      both asthmatic subgroups. Finally, spontaneous generation of SO inversely
      correlated with FEV1% prediction (r = 0.35, p < 0.01) in the asthma group. We
      conclude that worsening of airway obstruction in asthma is associated with
      increased spontaneous generation of SO by airspace leukocytes.

PMID- 8288954
TI  - von Willebrand factor binding to collagen in patients with end-stage renal
      disease.
AB  - Bleeding abnormalities are common in patients with end-stage renal disease
      (ESRD). Although von Willebrand factor (vWF) abnormalities have been suspected in
      patients with ESRD, none have been clearly defined. Because vWF function is
      related to its collagen-binding capacity, we investigated whether this parameter
      might be altered in patients with ESRD. We measured vWF binding to type III
      collagen and levels of vWF antigen and ristocetin cofactor in 20 patients
      undergoing hemodialysis before and after routine hemodialysis sessions, in 10
      patients with ESRD who had not previously undergone dialysis, and in 22 healthy,
      nonsmoking persons who served as controls. We found significant increases of vWF
      antigen levels in all patients with ESRD (undialyzed: mean, 6.4 +/- 3.0 U/ml, p <
      0.001; before dialysis: mean, 5.1 +/- 4.0 U/ml, p < 0.001; after dialysis: mean,
      4.8 +/- 3.4 U/ml, versus 0.81 +/- 0.26 U/ml in controls, p < 0.001). The
      ristocetin cofactor levels were increased in the patients who had not undergone
      dialysis (mean, 1.30 +/- 1.26 U/ml, p = 0.04), whereas both before and after
      hemodialysis groups (means, 0.71 U/ml and 0.75 U/ml, respectively) were not
      significantly different from controls (mean, 0.72 +/- 0.30 U/ml, p = 0.96 and p =
      0.8, respectively). Patients with ESRD who had not undergone dialysis showed no
      difference in vWF binding to collagen (mean, 1.21 +/- 0.63 U/ml) compared with
      the control group (mean, 1.16 +/- 0.13).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288955
TI  - The effects of anesthesia on malignant disease.

PMID- 8288956
TI  - Estrogen-induced pancreatitis: a caveat worth remembering.

PMID- 8288957
TI  - Agonist: gastric first pass metabolism of alcohol.

PMID- 8288958
TI  - Antagonist: the case against first-pass metabolism of ethanol in the stomach.

PMID- 8288959
TI  - Transforming growth factor-beta and the glomerular extracellular matrix in renal
      pathology.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctionally acting peptide
      with a broad spectrum of cellular targets. The biologic function of this peptide
      is currently widely studied. These studies reveal remarkable effects on
      proliferation, differentiation, migration, and production of many cell types.
      Among these effects, the regulatory function of TGF-beta in extracellular matrix
      homeostasis is thought to represent a major part of its action, mediating various
      other effects. Because disturbance of the regulation of extracellular matrix
      production is involved in various diseases, TGF-beta was expected to play a role
      in pathologic accumulation of extracellular matrix. By now, involvement of TGF
      beta in the development of pathologic matrix production is most clear in
      experimental glomerular diseases. In this review, various lines of evidence for
      such an involvement are presented. After a general introduction about the
      molecular structure of TGF-beta and its biologic function, the regulation of
      extracellular matrix production by TGF-beta is discussed, with special emphasis
      on the glomerulus. Finally, the involvement of TGF-beta in the development of
      glomerulosclerosis is considered. Because in vivo inhibition of TGF-beta action
      in animal models seems to prevent pathologic matrix accumulation, the possible
      role of TGF-beta as an important mediator in the development of
      glomerulosclerosis may have important implications for prevention of
      glomerulosclerosis in human renal disease. Extensive study of the in vivo
      regulation of TGF-beta activity, both in animal models and human diseases, will
      be necessary for further elucidation of pathogenetic mechanisms and possibilities
      for therapeutic intervention.

PMID- 8288960
TI  - Mechanisms of heat adaptation: thermotolerance and acclimatization.

PMID- 8288961
TI  - Anesthetic agents modify tissue proteinase inhibitor content and tumor behavior.
AB  - Anesthetic agents may modify the tissue content of low molecular weight
      proteinase inhibitors (mol wt less than 50,000) and affect the colonization and
      proliferation of B16-F10 melanoma cells in lungs. Lungs of female mice exposed to
      halothane in oxygen had significantly greater low molecular weight proteinase
      inhibitor activity than those from unexposed female mice. The amount of activity
      in male mice similarly exposed did not differ from unexposed controls. Lungs of
      exposed female mice also had greater activity as compared with males similarly
      exposed. No differences occurred in identical experiments with ketamine. High
      performance liquid chromatography revealed that the inhibitor in all groups of
      both sexes shared a major peak with a molecular weight similar to that of the
      trypsin inhibitor aprotinin. Female mice bearing B16-F10 melanoma cells and
      exposed to halothane in oxygen had significantly more small lung tumor nodules
      than tumor-bearing female mice injected with ketamine. However, the total number
      of nodules did not differ between the two groups. These observations support the
      hypothesis that stimulation of proteinase inhibitory activity by halothane in
      oxygen may be responsible for an inhibition of tumor cell proliferation,
      resulting in smaller tumor nodules and no effect on the incidence of
      colonization.

PMID- 8288962
TI  - Severe hypertriglyceridemia and pancreatitis when estrogen replacement therapy is
      given to hypertriglyceridemic women.
AB  - Our specific aim was to assess severe hypertriglyceridemia and pancreatitis that
      occurred when postmenopausal estrogen replacement therapy (ERT) or tamoxifen had
      been given by their physicians to women with preexisting, usually covert, primary
      familial hypertriglyceridemia. We retrospectively studied 31 women referred for
      diagnosis and therapy of hypertriglyceridemia over 2.75 years whose initial visit
      fasting plasma triglyceride levels were > 750 mg/dl. Of the 31 women with
      hypertriglyceridemia, 12 (39%) had been given exogenous estrogen by their
      physicians (11 ERT, one tamoxifen). Ten of the 12 women, while undergoing ERT,
      had triglyceride levels > 1200 mg/dl. In triglyceride referral categories 750 to
      1000, 1000-1500, and > 1500 mg/dl, 17% (2 of 12), 33% (3 of 9), and 70% (7 of
      10), respectively, of the 31 women with hypertriglyceridemia were receiving ERT.
      The higher the triglycerides were at referral, the greater was the likelihood
      that women were taking ERT (x2 = 6.6, p = 0.035). Four of the seven women with
      triglyceride levels > 1500 mg/dl while undergoing ERT were hospitalized with
      severe acute pancreatitis; another two had severe abdominal pain thought to be
      pancreatic in origin. To quickly lower dangerously high triglyceride levels, ERT
      was stopped in all 12 women. Lopid (1.2 to 1.5 gm/day) was given to the seven
      women not already taking it, and four were also given omega-3 fatty acids (4 to
      15 gm/day). Median plasma triglyceride level at the initial visit in the 12 women
      undergoing ERT was 1665 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288963
TI  - Endotoxin-induced pulmonary leukostasis in the rat: role of platelet-activating
      factor and tumor necrosis factor.
AB  - Injection of bacterial lipopolysaccharide (LPS) into experimental animals induces
      septic shock associated with the release of tumor necrosis factor (TNF) and
      platelet-activating factor (PAF). Because both TNF and PAF stimulate neutrophil
      adhesion to endothelial cells in vitro, and because neutrophils are important
      effector cells in sepsis-induced lung vascular injury, the role of TNF and PAF in
      LPS-induced lung neutrophil sequestration was investigated. Lung myeloperoxidase
      (MPO) activity was measured as a quantitative assessment of pulmonary
      leukostasis. Injection of Salmonella enteritidis LPS into rats caused dose
      dependent increases in lung MPO that peaked at 2 hours and persisted for up to 24
      hours. Injection of purified human recombinant TNF (2 to 200 micrograms/kg i.v.)
      mimicked the effect of LPS on lung MPO activity. Injection of synthetic PAF
      increased lung MPO only at the highest and lethal dose (10 micrograms/kg). Lower
      doses (0.1 and 1 microgram/kg) of PAF had no effect on lung MPO by itself and did
      not enhance LPS- or TNF-induced lung neutrophil sequestration. Furthermore,
      pretreatment of the rats with two different PAF receptor-antagonists, WEB 2086
      (10 mg/kg IP) and SRI 63-441 (10 mg/kg IP), failed to block LPS-induced (1 mg/kg)
      increase in lung MPO. These data suggest that TNF, not PAF, mediates LPS-induced
      pulmonary neutrophil sequestration in the intact rat.

PMID- 8288964
TI  - Toxic effects of dimethylthiourea in rats.
AB  - Dimethylthiourea (DMTU) is a small, highly diffusible molecule that effectively
      scavenges toxic oxygen metabolites in vitro and reduces oxidative injury in many
      biologic systems. Nonetheless, for unknown reasons, DMTU has occasionally failed
      to decrease damage in some systems where injury is presumed to be mediated by
      oxygen metabolites. We hypothesized that the inconsistent pattern of protection
      might partially reflect a direct toxicity of DMTU. Our results supported this
      premise. We found that rats treated with commonly used doses of highly purified
      DMTU had increased lung accumulation of intravenously injected iodine 125-labeled
      albumin (4 hours after DMTU treatment) and decreased blood glutathione levels (24
      hours after DMTU treatment) when compared with saline-injected control rats. In
      contrast, rats treated with dimethylurea, a analog of DMTU, did not develop
      increased accumulation of labeled albumin in the lungs or decreased blood
      glutathione levels. We conclude that DMTU has intrinsically toxic effects in rats
      and that DMTU toxicity may at times obscure its protective action.

PMID- 8288965
TI  - Cardiac resuscitation by retroaortic infusion of blood.
AB  - Current methods of closed-chest cardiac resuscitation generate coronary perfusion
      pressures that rarely exceed one fourth of normal, and this decreases with
      prolongation of cardiac arrest. The resuscitation effort is therefore almost
      uniformly unsuccessful when precordial compression is initiated after 8 minutes
      of untreated cardiac arrest. This report introduces a new option for cardiac
      resuscitation by infusion of oxygenated blood into the ascending aorta such as to
      transiently increase the pressure gradient for coronary perfusion. Thirty-six
      anesthetized, mechanically ventilated normovolemic rats were investigated.
      Cardiac arrest was induced with an alternating current delivered through an
      electrode catheter advanced into the right ventricle. Ventricular fibrillation
      was untreated for 4, 6, or 8 minutes, after which resuscitation was attempted
      without blood infusion, with infusion of oxygenated blood, or with infusion of
      oxygenated blood containing 30 mg/kg epinephrine. The boluses of blood were
      delivered through a catheter advanced from the right carotid artery into the
      ascending aorta. Except for mechanical ventilation and direct current precordial
      countershock for electrical defibrillation, no other mechanical resuscitation
      intervention, and specifically no precordial compression, was administered. None
      of six control animals that received either no retroaortic infusion or right
      atrial infusion was resuscitated after 4 minutes of untreated ventricular
      fibrillation. Each of five animals was successfully resuscitated by retroaortic
      infusion after 4 minutes of untreated cardiac arrest; one was resuscitated after
      6 minutes, and none was resuscitated after 8 minutes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8288966
TI  - Induction of endotoxin tolerance with monophosphoryl lipid A in peritonitis:
      importance of localized therapy.
AB  - Endotoxin is a principle mediator of septic shock during peritonitis. Induction
      of endotoxin tolerance with monophosphoryl lipid A (MPL), a nontoxic derivative
      of lipid A, improves survival from peritonitis. The induction of tolerance with
      intravenous versus intraperitoneal administration of MPL before peritonitis was
      compared. Mice were pretreated with varying doses of MPL (intravenously) and MPL
      (intraperitoneally) 48 hours before peritonitis was induced by cecal ligation and
      perforation. Survival was determined at 72 hours, and serum and peritoneal levels
      of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha)
      were assayed at 24 hours. Survival was 0% in control animals, 20% in MPL (100
      micrograms intravenously) animals, and 70% in MPL (100 micrograms
      intraperitoneally) animals (p < 0.05 versus control, MPL [intravenously]).
      Cytokine release was compared in control animals and animals receiving MPL 100
      micrograms (intraperitoneally) or MPL 100 micrograms (intravenously). In MPL
      (intraperitoneally)-treated animals, serum and peritoneal TNF-alpha levels, 160
      +/- 7 pg/ml and 204 +/- 25 pg/ml, were significantly lower than those in control
      animals, 429 +/- 34 pg/ml and 642 +/- 108 pg/ml, and MPL (intravenously)-treated
      animals, 302 +/- 68 pg/ml and 495 +/- 97 pg/ml, (p < 0.05). Similarly, IL-1 alpha
      levels were significantly lower in MPL (intraperitoneally)-treated animals than
      in control animals. Because the development of tolerance appears to be a cytokine
      mediated process, a subsequent experiment compared peritoneal and serum TNF-alpha
      and IL-1 alpha levels at 2 hours after MPL (intraperitoneally) or MPL
      (intravenously). Peritoneal TNF-alpha and IL-1 alpha release was greatest after
      MPL (intraperitoneally); serum levels were greatest after MPL
      (intravenously).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8288967
TI  - Sinus computerized tomography in primary hypogammaglobulinaemia.
AB  - Thirteen patients suffering from primary hypogammaglobulinaemia receiving
      intravenous immunoglobulin replacement therapy underwent computerized tomography
      of the paranasal sinuses. The CT scans were evaluated and related to clinical
      data from the patients, who were selected for study on the basis of having
      symptoms of rhinosinusitis. The scans varied from normal to demonstrating
      widespread sinus abnormality. There was no relationship between the scan findings
      and duration of ENT symptoms, range of current symptoms, or the interval between
      the onset of ENT symptoms and the start of intravenous immunoglobulin replacement
      therapy. It is nevertheless possible that prompt institution of replacement
      therapy, after correct diagnosis early in the course of the disease, may prevent
      the development of sinus disease refractory to such treatment.

PMID- 8288968
TI  - Altered dental sensation following intranasal surgery.
AB  - Some patients complain of altered sensation in the mouth following nasal surgery.
      A prospective study of 60 consecutive patients who underwent a total of 83
      intranasal procedures revealed that this was a common complication, particularly
      following submucous resection (SMR) or intranasal antrostomies. The area affected
      by pain/parasthesia appears to be anatomically related to the surgical
      procedure(s) performed.

PMID- 8288969
TI  - Twelve cases of glottic carcinoma in situ treated by radiotherapy: an observation
      on clinical course versus response.
AB  - Carcinoma in situ (CIS) of the glottis is an uncommon and poorly understood
      condition with few, large, long-term studies. Twelve cases are presented which
      were treated with radiotherapy. At three-year follow-up all the patients are
      disease free and in 83 per cent the mucosa has returned to normal. The
      alternative methods of treatment are discussed.

PMID- 8288970
TI  - Trismus in patients with malignant tumours in the head and neck.
AB  - In order to elucidate the causal mechanism of trismus in head and neck cancer, 21
      patients manifesting trismus out of 212 patients with malignant tumours in the
      head and neck (treated in Tokyo University Branch Hospital from 1983 to 1991)
      were reviewed. Nine patients developed trismus either by infiltration of the
      muscles of mastication or by reflex spasm. Trismus was considered to have
      developed as a result of irradiation in five cases and of surgical intervention
      in seven cases. In some cases of oropharyngeal cancer, CT revealed no evidence of
      tumour invasion into the infratemporal fossa when trismus occurred, suggesting
      that trismus was caused either by the reflex spasm of muscles or by microinvasion
      too small to be seen in CT films. Maxillary sinus tumours were often without
      trismus even when they extended posteriorly to the infratemporal fossa.

PMID- 8288971
TI  - Gastric pull-up by eversion stripping of oesophagus.
AB  - Gastric pull-up is a reliable method of one-stage reconstruction following total
      laryngopharyngoesophagectomy (TLPE). However, the technique of blunt finger
      dissection for extrapleural extraction of the oesophagus is liable to produce
      chest complications like pneumothorax. We report a series of 45 patients who
      underwent gastric pull-up using the technique of oesophageal extraction by
      stripping which produced virtually no thoracic complications. This simple
      technique has greatly reduced morbidity associated with gastric pull-up.

PMID- 8288972
TI  - Fine needle aspiration cytology of salivary gland lesions reported immediately in
      a head and neck clinic.
AB  - This paper describes the application of fine needle aspiration cytology (FNAC)
      performed on 92 patients with salivary gland lesions in a Head and Neck Surgery
      Clinic. The aspirates were immediately reported by a cytopathologist and the
      reports conveyed to the surgeon during the same clinic visit. FNAC results were
      then compared with histology in those patients who underwent surgery and with the
      clinical course of the disease at subsequent clinic visits in patients where
      surgery was not performed. The cytological diagnosis was incorrect in five cases,
      one of which was a false negative result. There were no false positive results.
      The sensitivity was 90.9 per cent and the specificity 100 per cent. This rapid
      report system of fine needle aspiration cytology has been found to be safe, free
      of complications, and helpful in the planning of treatment.

PMID- 8288973
TI  - Conchal flap meatoplasty.
AB  - A meatoplasty technique is described which has proved successful in the treatment
      of chronic otitis externa. The procedure opens the superficial meatus by
      eliminating the sharp rim at the junction of the conchal bowl and the posterior
      canal wall cartilage; thinning the skin and increasing the circumference of the
      external auditory orifice.

PMID- 8288974
TI  - Foley catheter fixation in posterior epistaxis.
AB  - An improved technique for fixation of a Foley catheter in posterior epistaxis is
      presented. It has the advantage of rigidity combined with a narrow diameter.

PMID- 8288975
TI  - Sensorineural hearing loss in neurobrucellosis.
AB  - A case of neurobrucellosis presenting to the otologist with sensorineural hearing
      loss (SNHL) as the predominant clinical feature is reported. The diagnostic
      features and treatment options are discussed and the need for prolonged
      combination treatment to prevent relapse and further deterioration of hearing
      stressed. SNHL in neurobrucellosis has hitherto been reported principally in
      neurology literature as something of an incidental finding and so escapes the
      attention of otologists. It is hoped that this report will alert otologists in
      areas where brucellosis is endemic to the need to include tests for brucellosis
      in the routine diagnostic screening for SNHL. Practitioners in other locations
      should also consider this possibility when dealing with patients who have visited
      or lived in endemic regions.

PMID- 8288976
TI  - Ligation of the internal jugular vein in venous hum tinnitus.
AB  - Vascular anomalies, extracranial and intracranial arteriovenous malformations as
      well as glomus jugulare tumour are well known causes of pulsatile tinnitus. Of
      late, benign intracranial hypertension has been stated to be a more common cause.
      However, tinnitus arising from and within the internal jugular vein has been
      reported only infrequently. Previously known as cephalic bruit and essential
      objective tinnitus, the venous hum tinnitus presents as pulse synchronous
      unilateral objective tinnitus. Ligation of the internal jugular vein appears to
      be a successful treatment. Two cases are presented.

PMID- 8288977
TI  - Vascular malformation of the internal auditory canal.
AB  - A report of a case with a vascular malformation of the internal auditory canal
      (IAC) is presented. A review of the literature of this rather rare lesion is also
      made in an attempt to outline its clinical features, radiological diagnosis and
      management. The differential diagnosis and distinction between vascular
      malformations and other internal auditory canal tumours are discussed.

PMID- 8288978
TI  - Periorbital abscess due to ethmoiditis in a neonate.
AB  - Orbital complications of ethmoiditis are not uncommon in children. They are,
      however, much rarer in the very young. A case is presented in which a neonate of
      gestational age 39 weeks developed a periorbital abscess. The relevant literature
      is reviewed with respect to embryology, aetiology and treatment.

PMID- 8288979
TI  - Melanotic neuroectodermal tumour of infancy.
AB  - The melanotic neuroectodermal tumour of infancy is a rare, pigmented neoplasm
      that most frequently arises from the anterior maxillary alveolar ridge. It
      presents in the first few months of life, and usually follows a benign course. A
      classical case is presented and the clinical, radiological and pathological
      characteristics are discussed. The importance of early conservative surgical
      excision is emphasized with, in general, a good prognosis. This tumour, which
      many otolaryngologists may not be familiar with, should be included in the
      differential diagnosis of head and neck neoplasms in infants and young children.

PMID- 8288980
TI  - Extramedullary plasmacytoma of the larynx.
AB  - A case of IgD myeloma in a 54-year-old male with a long-standing history of
      extramedullary plasmacytoma involving the larynx is reported. The patient was
      treated with radiation therapy and laryngectomy. Twelve years later, he
      complained of nasal bleeding. On examination he was found to have large masses in
      the left nasal cavity and in the left supraclavicular region. Histological
      examination of both lesions showed plasmacytoma. Serum immunoglobulin studies
      revealed an IgD monoclonal spike of the lambda type. Bence-Jones protein was
      present. Using the immunoperoxidase staining technique, cytoplasmic monoclonal
      IgD was detected.

PMID- 8288981
TI  - Primary tracheal tuberculosis in an otherwise healthy 65-year-old Caucasian
      woman.
AB  - We report a case of primary tracheal tuberculosis that presented with a hard,
      fixed lymph node in the right supraclavicular fossa, and progressive dysphagia
      due to an inflammatory mass caused by a tuberculous lesion in the trachea. This
      case underlines the old adage that tuberculosis is 'the great masquerader'.

PMID- 8288982
TI  - Per-oral excision of a pharyngeal branchial cyst after MRI study.
AB  - A per-oral approach to pharyngeal branchial cysts is possible, and ideal when
      they are placed medially to the pharyngeal constrictors and no fistular duct is
      connected to the mass. At present MRI is found to be the best means of achieving
      the correct diagnosis of morphology and site.

PMID- 8288983
TI  - Dysphagia caused by a foreign body in the thyroid.

PMID- 8288984
TI  - Vomiting in pregnancy resulting in oesophageal perforation in a 15-year-old.
AB  - Spontaneous perforation of the oesophagus is extremely rare in children, as is
      perforation due to vomiting in pregnancy. We report the case of a 15-year-old in
      whom vomiting in early pregnancy resulted in oesophageal perforation with
      subcutaneous emphysema causing marked facial swelling in the absence of other
      signs. The more common clinical presentation of spontaneous oesophageal rupture
      (Boerhaave's syndrome) is discussed.

PMID- 8288985
TI  - Histiocytosis: an unusual cause of dysphagia, hoarseness and stridor.
AB  - We present a patient with established histiocytosis who developed dysphagia,
      retching, regurgitation, hoarseness and stridor. These symptoms were managed with
      carbon dioxide laser vaporization, electively on three occasions, and once as an
      urgent procedure, while awaiting radiotherapy, to control her airway.
      Histiocytosis is a rare cause of a number of otolaryngological syndromes, but
      there has been no previous record of this disease causing laryngopharyngeal
      symptoms. This paper discusses the classification of histiocytosis, and describes
      our management of this rare and intriguing case.

PMID- 8288986
TI  - Cowden's disease--its importance for otolaryngologists.
AB  - Cowden's disease is a rare predominantly inherited disease, characterized by
      mucocutaneous lesions, gastrointestinal polyposis and benign or malignant thyroid
      and breast tumours. The report deals with a typical case of this disease with
      emphasis on its importance for otolaryngologists.

PMID- 8288987
TI  - MRI features in a malignant glomus jugulare tumour.
AB  - Magnetic resonance imaging (MRI) features in a case of malignant glomus jugulare
      tumour are reported. Chemodectomas are benign in 95 per cent of cases and
      malignant in five per cent. Only one case report of CT findings in this unusual
      CP angle tumour with pulmonary metastases has been cited in the literature. It is
      concluded that MRI can provide useful information about the nature of
      chemodectomas although it cannot distinguish between benign and malignant
      tumours, except when regional lymph nodes are involved or when distant metastases
      exist.

PMID- 8288988
TI  - Primary synovial sarcoma of the middle ear.
AB  - Synovial sarcoma is a soft tissue malignancy which most commonly affects the
      lower limbs of young adults and rarely occurs in the head and neck region. The
      term synovial sarcoma may be a misnomer as most of these tumours occur in tissues
      not known to contain synovial tissue. There has only been one previously reported
      case affecting the middle ear, which was metastatic, and we report the first case
      of primary synovial sarcoma of the middle ear.

PMID- 8288989
TI  - Benign hamartomatous polyp of the palatine tonsil.
AB  - A rare and possibly unique benign polypoid tumour of the palatine tonsil is
      described. It contained the two basic tissue types of the tonsil--lymphoid and
      epithelial--in the characteristic close anatomical relationship of tonsillar
      tissue. The features of this rare lesion lend support to the hypothesis that
      benign tumours of the tonsil may be hamartomas of tonsil or branchiogenic
      remnants rather than true neoplasms.

PMID- 8288990
TI  - Post-irradiation leiomyosarcoma of the maxilla.

PMID- 8288991
TI  - When is a decibel not a decibel?: The application of decibel scales and
      calibration in clinical audiology.
AB  - Decibel scales are a very important but potentially confusing subject for the
      clinician. Misunderstanding can, at worst, lead to inappropriate management which
      is detrimental to the patient. This paper sets out, from the viewpoint of an
      acoustician, the calibration and meaning of the various decibel scales in common
      use, shows how they are applied to the clinical setting, and explains their
      limitations.

PMID- 8288992
TI  - Prevalence and aetiology of profound deafness in the general population of
      Sichuan, China.
AB  - People with profound deafness were surveyed in the general population of Sichuan.
      The results showed that the overall prevalence in Sichuan was 0.186 per cent
      (236/126,876) of the general population, males 0.212 per cent (135/63,741),
      females 0.159 per cent (101/63,135) (p < or = 0.05). Two hundred and fifteen (92
      per cent) cases were older than 10 years, but 227 (96 per cent) lost their
      hearing under the age of 10 years, 192 (80 per cent) under five years, and 104
      (44 per cent) were congenital. There was no significant difference in prevalence
      of deafness between the population located in urban and rural areas. However, the
      population living in the flat area and mountain area had a much higher prevalence
      than that of the hill people (p < or = 0.05). Amongst the nationalities
      investigated, there existed significant differences in prevalence. Both the
      population of the Hui and the Lisu presented a significantly higher prevalence of
      profound deafness than that of the others. In aetiology, genetic factors may
      account for 43 per cent (101/236) of the cases, amongst which, autosomal
      recessive (AR) deafness is 92 per cent (95/104) and autosomal dominant (AD) 5.4
      per cent. Environmental factors were thought to be responsible for 35.6 per cent
      (84/236) of cases, including infectious diseases (31 per cent), ototoxic
      antibiotics (2.6 per cent), injury (1.7 per cent), and asphyxia (0.4 per cent).
      The number of cases of unknown origin were 20.3 per cent. It is suggested that,
      in China, the importance of genetic factors in hearing impairment should be
      emphasized. In addition, infectious diseases and ototoxicity play an important
      role in causing deafness.

PMID- 8288993
TI  - Type II collagen autoimmunity and Meniere's disease.
AB  - Antibodies to type II collagen have been reported by some authors to be raised in
      patients with Meniere's disease. In this study the antibody levels to type I and
      II collagen have been measured in 37 patients with Meniere's disease and 20
      controls, using a solid-phase, double-antibody, enzyme-linked, immunoassay. No
      significant difference in antibody levels between the two groups was found. These
      findings do not support previously reported work which suggests that some cases
      of Meniere's disease are due to type II collagen autoimmunity.

PMID- 8288994
TI  - Extracranial and intracranial complications of suppurative otitis media. Report
      of 102 cases.
AB  - During the eight-year period, 1983-1990, 102 cases of intracranial (IC) and
      extracranial (EC) complications from 17 144 suppurative otitis media were
      reviewed. The prevalence of each complication was 0.24 and 0.45 per cent
      respectively. Facial paralysis, subperiosteal abscess and labyrinthitis were the
      common complications among the EC group, while meningitis and brain abscess were
      common in the IC group. Twenty five per cent of the EC group and 44 per cent of
      the IC group had more than two complications. The reliable warning signs and
      symptoms for IC complications were fever, headache, earache, vestibular symptoms,
      meningeal signs and impairment of consciousness. Proteus spp., Pseudomonas
      aeuruginosa and Staphylococcus spp. were the commonest organisms isolated from
      both groups. Cholesteatoma and granulation/polyp in the middle ear/mastoid were
      the major findings in both patient groups. Mortality rate in the IC group was
      18.6 per cent. Morbidity rate in each group was 14.3 per cent (EC) and 27.9 per
      cent (IC) respectively. Epidemiological presentations, clinical features and the
      result of treatment are discussed.

PMID- 8288995
TI  - Unusual cerebello-pontine angle tumours.
AB  - Fifty-nine unusual cerebello-pontine angle tumours have been studied. These
      lesions represent 19.3 per cent or 1 in 5 of a series of 305 cerebello-pontine
      angle tumours of which the rest, 246 (80.7 per cent), were acoustic neuromas. An
      analysis of the relative incidence, histology and presenting clinical features
      has been carried out. The various radiographical features and imaging techniques
      used to diagnose these fascinating tumours have been described and also the
      otoneurosurgical procedures necessary to excise them.

PMID- 8288996
TI  - Eustachian tube submucosal glands in normal and pathological temporal bones.
AB  - Histological data concerning the structure and the topographical distribution of
      the eustachian tube submucosal glands is presented in 94 serially-sectioned
      temporal bones with and without otitis media. The vast majority of the tubal
      glands are located adjacent to the nasopharynx in the pharyngeal and midportion
      regions. Mixed glands which contain equal amounts of mucoid and serous elements
      are found in all age groups, in most specimens, either with or without otitis
      media. Furthermore, the glandular tissue, along these two medial regions of the
      tube, does not disclose significant quantitative differences between normal and
      inflamed specimens. Temporal bones without otitis media harbour few glands in the
      lateral four regions of the tube, while those with otitis media show a moderate
      increase of gland formation which is more noticeable in the pretympanum than in
      the regions around the isthmus (pre-isthmus, isthmus and post-isthmus regions).
      It is apparent that chronic inflammatory conditions like simple chronic otitis
      media and secretory otitis media are more often accompanied by gland formation,
      along the lateral four regions of the tube than acute otitis media.

PMID- 8288997
TI  - Pressure exerted by head bandages used in otological surgery.
AB  - The pressure exerted by head bandages at the operation site following ear surgery
      was measured using a balloon catheter and pressure transducer. The initial
      pressures achieved, their diminution with time and the relationship of pressure
      to the induction of headache in the patient were studied. The principal findings
      were that the standard otological head bandage is rarely tight enough to prevent
      haematoma formation, bandages have lost their efficacy after the first hour and
      headaches are associated with a significantly higher initial bandage pressure.

PMID- 8288998
TI  - Radical mastoidectomy: its place in otitic intracranial complications.
AB  - Standard recommended treatment for patients with intracranial complications from
      otitis media, has been radical mastoidectomy, whether cholesteatoma is present or
      not. This was established in the pre-antibiotic era to improve survival. Over a
      six-year period, from January 1985 to December 1990, 268 patients were admitted
      with intracranial and extracranial complications of otitis media. The prospective
      treatment consisted of antibiotics and surgery. Surgery entailed mastoidectomy
      and drainage of intracranial collections of pus in all patients. However,
      prospectively in these patients the ear pathology and not the complication
      dictated the type of mastoidectomy performed. Cortical mastoidectomy was
      performed in non-cholesteatomatous ears and radical mastoidectomy in
      cholesteatomatous ears. Recurrence of intracranial complications occurred in only
      four patients (two per cent), a temporal lobe cerebritis in the non
      cholesteatomatous ear group, and, a temporal lobe abscess, posterior fossa
      abscess and subdural empyema in the cholesteatomatous ear group. The temporal
      lobe cerebritis settled on intravenous antibiotics whilst the temporal lobe
      abscess, posterior fossa abscess and subdural empyema required redrainage. In
      none of these was the ear surgery revised. There were 15 deaths (eight per cent),
      all occurring in patients with intracranial complications, 12 associated with
      brain abscess, two with subdural empyema and one with meningitis. Eight were from
      the non-cholesteatomatous group and seven from the cholesteatomatous group. The
      mortality was directly related to the patients consciousness level on admission
      and not to the type of ear pathology. It can therefore be concluded that radical
      mastoidectomy is unwarranted in the non-cholesteatomatous ear, even with an
      otogenic intracranial complication.

PMID- 8288999
TI  - Observer variations in the evaluation of facial nerve function after acoustic
      neuroma surgery.
AB  - This investigation was performed in order to evaluate the observer variations in
      facial nerve function after surgery for an acoustic neuroma. From 1976-90, 507
      patients were operated on by the same surgical team (M.T. and J.T.) using a
      translabyrinthine approach. One hundred and forty-four patients living in
      Copenhagen City and County were invited for interview and objective examination.
      Only 128 patients attended the interview and examination which were carried out
      by the same ENT physician. Data concerning observation of the facial nerve
      function only is presented. Its function was clinically evaluated (using the
      House and Brackmann (1985) grading scale) by two different observers i.e. the ENT
      physician and one of the surgeons. The patients were asked face-to-face with the
      ENT physician to estimate the degree of facial nerve function according to a 0
      100 per cent scale. Comparing normal and abolished facial nerve function the
      judgments of the ENT physician and the surgeon agreed with the patient's own
      evaluation.

PMID- 8289000
TI  - Cerebrospinal fluid (CSF) otorhinorrhoea following vestibular schwannoma surgery
      treated by extended subtotal petrosectomy with obliteration.
AB  - Extended subtotal petrosectomy as a treatment for persistent cerebrospinal fluid
      (CSF) otorhinorrhoea is presented. Four patients were successfully operated on by
      this technique, all previously having undergone suboccipital removal of
      vestibular schwannoma: other interventions used had failed to seal the fistulae.
      The internal auditory canal was the usual pathway for CSF leakage as well as
      retrosigmoid, retrolabyrinthine, retro- or perifacial cells. Total exenteration
      of middle ear and mastoid cell tracts, skeletonization of sigmoid sinus, jugular
      bulb and facial nerve, drilling out of semicircular canals, vestibule, and
      cochlea, and skeletonization of the internal auditory canal, followed by
      obliteration, are the main steps of this approach.

PMID- 8289001
TI  - Concho-antropexy or total inferior turbinectomy for hypertrophy of the inferior
      turbinates? A prospective randomized study.
AB  - Twenty-five patients with bilateral nasal obstruction due to hypertrophy of the
      inferior turbinates were entered into a prospective study to compare the efficacy
      and the associated complications of total inferior turbinectomy and concho
      antropexy. We found no significant statistical difference in the efficacy of
      these procedures in relieving nasal obstruction and discharge (p > 0.5). Total
      inferior turbinectomy was associated with more post-operative pain (p < 0.05) and
      with long-term dryness and crusting (p < 0.05) which were statistically
      significant. This is the first trial where concho-antropexy and total inferior
      turbinectomy are compared.

PMID- 8289002
TI  - Squamous cell carcinoma of the tonsillar region and the base of the tongue: a
      morphological and immunohistochemical comparative pilot study.
AB  - Sixteen squamous cell carcinomas of the tonsillar region and 13 carcinomas of the
      base of the tongue were studied in a search for significant differences between
      the tumours of these two oropharyngeal subsites, which are known to carry a
      significantly different prognosis. The characteristics of the tumour cells and
      the tumour-host relationship were scored on H & E-stained slides, as well as on
      slides stained with a panel of antibodies. The results obtained were cross
      tabulated and analysed with respect to the subsite. Ten variables were tested:
      cytonuclear pleomorphism, mitotic activity, the presence of atypical mitoses,
      keratinization, tumour grade, presence of eosinophils, severity of inflammatory
      response, and the expression of keratin-10, blood group antigens and collagen IV.
      When split up by site, only cytonuclear pleomorphism revealed a significant
      difference, tonsillar carcinomas more often exhibiting marked pleomorphism (p =
      0.04). Despite having some prognostic relevance for squamous cell carcinomas of
      the head and neck, the variables tested could not provide an explanation for the
      difference in biological behaviour of the tumours studied.

PMID- 8289003
TI  - Fistulae following laryngectomy in patients treated with irradiation.
AB  - The development of fistulae following 197 consecutive laryngectomies performed
      from 1980 to 1987 have been examined. Fistulae were present in 28 patients (14
      per cent). Age, T-classification, daily level of radiation dose and the time
      lapse between diagnosis and operation did not seem to influence the rate of
      fistula development. The study indicates that there is a two to three per cent
      risk of fistula development when a primary laryngectomy is performed. Fistula
      formation increased to about 10 to 12 per cent following radiotherapy, with an
      additional increase whenever previous operations on the neck had been done and/or
      if the disease demanded more extensive surgery. The study also indicates that the
      risk for fistula development is less when an experienced surgeon performs the
      operation.

PMID- 8289004
TI  - Photodynamic therapy of malignant and premalignant lesions in patients with
      'field cancerization' of the oral cavity.
AB  - The management of patients with 'field cancerization' of the oral mucosa, with
      multicentric foci of invasion, presents a considerable problem for the head and
      neck surgeon. Surgical resection of synchronous or metachronous primary squamous
      cell carcinomas, along with adjacent premalignant lesions, is likely to be
      associated with considerable mutilation. Photodynamic therapy (PDT) has been
      shown to be of value in the treatment of superficial tumours in the upper
      aerodigestive tract, with excellent healing of treated areas. This study reports
      the use of PDT to treat 11 patients with 'field cancerization' occurring in the
      oral cavity. Six patients had multiple primary cancers and five had single
      primary tumours. All had associated areas of leukoplakia. Each received Photofrin
      2 mg/kg 48 hours prior to photoirradiation with 50-100 J/cm2 red laser light by
      surface illumination. Six to eight weeks later treated areas in 10 of the 11
      patients showed a complete response to PDT; one patient had areas of residual
      leukoplakia. Two patients developed further areas of leukoplakia or erythroplakia
      within 12 months but no patient has had evidence of recurrent invasive carcinoma
      in the treated areas. Longer term follow-up will be necessary to exclude further
      recurrence. It is concluded that PDT offers an effective repeatable treatment
      option, whether on its own or as an adjunct to local excision, for patients with
      'field cancerization' of the oral cavity.

PMID- 8289005
TI  - Pre-operative haemoglobin estimation in paediatric ENT surgery.
AB  - Estimation of haemoglobin is still undertaken routinely before ENT surgery in
      many centres despite evidence that it is unnecessary, traumatic and expensive.
      The haemoglobin was estimated of all 372 children about to undergo ENT surgery in
      a busy district general hospital over a one year period. No child was noted to be
      clinically anaemic, and no child had a haemoglobin of less than 9 g/dl. Of 18
      children with a haemoglobin level of 10.5 or less, 10 had their operations
      postponed and eight did not. There were no complications in the latter group. We
      can find no published evidence that operating on children with mild anaemia is
      unsafe. Ceasing routine pre-operative haemoglobin estimation would safely save an
      estimated 9000 pounds per year in our unit.

PMID- 8289006
TI  - 'The holiday plug': a temporary solution to the problem of the leaking voice
      prosthesis.
AB  - Tracheo-oesophageal prostheses are commonly inserted in patients following total
      laryngectomy to improve the quality of the voice. Unfortunately the device
      eventually fails and requires replacement. A valve change, although well
      tolerated by patients, necessitates an out-patient visit and delay in its
      replacement can lead to problems of pneumonia or dehydration. In this short paper
      we describe a simple temporary solution for a leaking valve and recommend its use
      in patients who are delayed in returning to the unit for example when on holiday.

PMID- 8289007
TI  - Middle ear lipoma.
AB  - We report a case of primary middle ear lipoma diagnosed in the right ear of a
      five-year-old child with concurrent bilateral middle ear effusions. The lipoma
      occupied a site favoured by congenital cholesteatoma and was occlusive to the
      eustachian tube contributing to its dysfunction. This is the first case of de
      novo middle ear lipoma diagnosed in the UK, and the third in world literature.
      Our CT scans are suggestive of a similar but smaller lesion in the left ear of
      the same child.

PMID- 8289008
TI  - An unusual cause of benign paroxysmal positional vertigo.
AB  - Benign paroxysmal positional vertigo (BPPV) is a self-limiting condition
      characterized by vertigo and nystagmus induced by certain head positions. The
      most common causes of BPPV are post-traumatic following head injury and post
      viral labyrinthitis. We present an interesting case of BPPV following an
      otherwise uneventful neurosurgical removal of a parietal osteoma using hammer and
      chisel. Caution should be exercised during such procedures as disabling vertigo
      can result for a considerable period of time.

PMID- 8289009
TI  - Haemangiopericytoma of the parotid salivary gland: report of a case with
      literature review.
AB  - Haemangiopericytoma is a rare, soft tissue, tumour with unpredictable biological
      behaviour. A case of haemangiopericytoma of the parotid salivary gland is
      reported. The clinical, surgical and histological features are described.

PMID- 8289010
TI  - Extra-pharyngeal neck pathology complicating pharyngeal pouch surgery.
AB  - One case each of: (1) low grade thyroid lymphoma; (2) supraclavicular and para
      oesophageal metastasis of a uterine adenocarcinoma; and (3) recurrent
      multinodular goitre have been encountered in very intimate relationship with the
      neck of a pharyngeal pouch within the tracheo-oesophageal gutter raising the
      possibility that the two conditions were interrelated. The practical importance
      of these cases is that a surgeon excising a pouch from the neck ought to be able
      to resect a thyroid lobe should it prove necessary, and occasionally endoscopic
      diverticulotomy is the only reasonable option.

PMID- 8289011
TI  - Malignant mesenchymoma of the retropharyngeal space.
AB  - Malignant mesenchymoma is a very rare head and neck tumour. To date only 15 cases
      have been reported in world literature and all in children under 16 years of age.
      We present here a case of a 40-year-old man with malignant mesenchymoma of the
      retropharyngeal space. The clinical picture is that of progressive dysphagia,
      voice change, snoring and dyspnoea. CT scan showed a soft tissue space-occupying
      lesion of the retropharyngeal space which enhanced very well with intravenous
      contrast. The tumour was excised in toto and the patient given post-operative
      radiotherapy. Histopathology showed two unrelated differentiated tissue types
      (bone and fat) in addition to the fibrosarcomatous element thus satisfying
      Stout's criteria (Stout, 1948) for a diagnosis of malignant mesenchymoma.

PMID- 8289012
TI  - Cervicofacial actinomycosis: an unusual cause of submandibular swelling.
AB  - Two cases of cervicofacial actinomycosis, resulting in submandibular swelling,
      are presented. How actinomycosis may present under the guise of malignancy is
      well demonstrated. Factors predisposing to the condition, difficulties with
      diagnosis, isolation methods of the causative organism and treatment of the
      disease, are discussed.

PMID- 8289013
TI  - Tumours metastasizing to the head and neck--a report of seven cases.
AB  - Metastatic tumours involving the head and neck region are rare. Over the past 18
      years, seven such cases were treated at our clinic. Of those, four were in one of
      the paranasal sinuses, three had arisen from a primary hepatocellular carcinoma
      and one from an osteogenic fibrosarcoma of the leg. In the remaining three cases,
      metastases to the larynx, the tonsil, and the parotid gland arose from a primary
      renal cell carcinoma, a thyroid carcinoma, and a breast carcinoma, respectively.
      In metastatic tumours, the primary site can often be identified by the
      histopathological features. Accordingly, when malignant head and neck tumours are
      suspected of being metastatic in character, it is important to search carefully
      for the primary site.

PMID- 8289014
TI  - Papillary carcinoma in a thyroglossal duct remnant with normal thyroid gland.
AB  - Carcinoma in the thyroglossal duct remnant is relatively uncommon. Since the
      first report by Uchermann (1915), more than 150 cases of carcinoma have been
      reported, and the majority have been papillary thyroid carcinomas (Li Volsi et
      al., 1974; McNicol et al., 1988). In this report, we present a case of papillary
      carcinoma in the thyroglossal duct with a normal thyroid gland.

PMID- 8289015
TI  - Undifferentiated carcinoma with lymphoid stroma of the parotid gland.
AB  - A rare undifferentiated carcinoma with lymphoid stroma (UCLS) of the parotid
      gland is described in a white Turkish patient. The raised serum IgG to Epstein
      Barr virus capsid antigen suggests a causal relationship between Epstein-Barr
      virus and this type of salivary gland carcinoma. Some clinical features are
      briefly reviewed.

PMID- 8289016
TI  - Otological relief work in Romania.
AB  - The experiences of an otological surgical team during a brief visit to northern
      Romania are discussed. The importance of careful assessment of local deficiencies
      and needs is emphasized and sources of funding and equipment for use during such
      a trip are discussed.

PMID- 8289017
TI  - Sudden sensorineural hearing loss in sickle cell disease.

PMID- 8289018
TI  - Canal master instrumentation: an in vitro study of separation frequency.
AB  - Ninety resin blocks were instrumented by three different operators using the
      Canal Master Instrumentation system. The frequency of file separation among three
      operators of varying endodontic experience (novice dental student to endodontist)
      was compared. Twenty-one of 87 (24%) of the instruments were separated. The #50
      Canal Master file failed most frequently (5 of 21). Three ledges (3 of 90
      samples) were created by the novice operator with the Canal Master rotary
      instruments which could not be bypassed. Separation rates among the operators
      ranged from 12 of 27 (novice) to 4 of 30 (endodontist). The results suggest that
      the Canal Master file may be prone to fracture in vitro and that there may be a
      "learning curve" to proficient Canal Master use.

PMID- 8289019
TI  - Prognosis of intracoronal bleaching with sodium perborate preparation in vitro: 1
      year study.
AB  - Bleaching materials containing hydrogen peroxide have been used for treating
      discolored nonvital teeth but their use was occasionally associated with external
      root resorption. In a previous study it was found that the immediate results of
      bleaching teeth in vitro were equal for sodium perborate mixed with either water
      or hydrogen peroxide. The purpose of this study was to compare the bleaching
      prognosis of sodium perborate mixed with water or hydrogen peroxide over a 1-yr
      period. Extracted human teeth with intact crowns were discolored with human
      erythrocytes and bleached by sodium perborate mixed with either 30% hydrogen
      peroxide (group A), 3% hydrogen peroxide (group B), or water (group C). The
      bleaching materials were placed in the pulp chambers of the discolored teeth and
      sealed with IRM. They were replaced with fresh preparations after 3 and 7 days.
      After 14 days the coronal access cavities were sealed with composite resin and
      the teeth photographed with a color slide film under standardized conditions. The
      teeth were stored in artificial saliva for 1 yr and photographed after 3, 6, and
      12 months. Two separate evaluators ranked the teeth by comparing them with the
      shades before and after bleaching. The bleaching success rates of the tested
      groups at each time interval were compared and analyzed statistically. It was
      found that after 1 yr all of the teeth in groups A and C maintained their shades.
      In 20% of the teeth in group B there was color regression. Statistically, these
      differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289020
TI  - Histomorphometric study of dental pulp during orthodontic tooth movement.
AB  - Orthodontic tooth movement has been implicated in secondary changes to the dental
      pulp. The purpose of this study was to correlate the effects of orthodontic tooth
      movement on the dental pulp by histomorphometric parameters. Four groups, each
      consisting of 36 male adult Sprague-Dawley strain rats, were studied with
      differing force magnitudes. These included a sham group in addition to groups
      with bilaterally placed appliances activated to 20, 40, and 60 g of initial force
      designed to mesially tip the maxillary first molars. Six rats were killed at 1,
      3, 5, 7, 10, and 14 days. Specimens were fixed, embedded, and stained with
      tetrachrome. Pulpal measurements were made with an image analyzer and included
      changes in predentin and vascularity. Findings indicated a significant increase
      (p < or = 0.05) relative to time and force magnitude in capillary number. An
      initial pulpal hyperemia was observed following activation of orthodontic force
      which was unrelated to force magnitude. A force-dependent increase in predentin
      width was measured at the peak of the tooth movement cycle.

PMID- 8289021
TI  - Chelate root filling cements: biological properties.
AB  - The purpose of this study was to test in vivo and in vitro the toxicity and the
      antibacterial activity of an experimental chelate cement (HN cement) using zinc
      oxide-eugenol cement as a reference. After subcutaneous injection of the
      spatulated HN cement paste in rats, it induced markedly less tissue injuries than
      did the zinc oxide-eugenol cement. In toxicity tests using cultures of human
      fibroblasts, the HN cement was found to be less toxic than the reference cement.
      Bacteriologically, blood agar plates inoculated with Streptococcus sanguis,
      Staphylococcus aureus, and the anaerobic Prevotella intermedia developed
      inhibition zones between 3 and 12 mm upon application of both cements. Both
      demonstrated marked bacteriostatic and bactericidal properties.

PMID- 8289022
TI  - Master core apical movement during compaction: evaluation of two in vitro models.
AB  - This study evaluated two in vitro models (a split hard metal model and a split
      natural tooth model) for the assessment of master cone apical movement. Gutta
      percha cones were fitted 0.5 and 1.0 mm short of the apical ends of the
      artificial canals. Photographs were taken before and after vertical or lateral
      compaction and measurements were made. The results demonstrated no significant
      difference between the two models.

PMID- 8289023
TI  - Correlation between thermal sensitivity and microorganisms isolated from deep
      carious dentin.
AB  - The correlation between thermal sensitivity and the microorganisms present in 29
      deep carious lesions was studied. The numbers of lactobacilli and total Gram
      positive rods in the carious lesions were found to be negatively related to the
      length of pain triggered by cold and heat stimulants. The presence of Gram
      positive cocci and non-black-pigmented Bacteroides were positively associated
      with both cold and heat sensitivities. Black-pigmented Bacteroides, Streptococcus
      mutans, and total anaerobic colony counts were positively related to the heat
      sensitivity. Recovery of Fusobacterium nucleatum, Actinomyces viscosus, and
      enterics on the selective plates was associated with cold sensitivity. Total
      counts of Gram-positive cocci and Gram-negative rods on the anaerobic
      nonselective medium were positively related to the cold sensitivity. It appeared
      that teeth with low numbers of lactobacilli in the carious lesions usually
      responded to thermal tests with longer duration of pain. Conversely, teeth with
      high numbers of lactobacilli in the carious lesions usually responded with
      shorter duration of pain.

PMID- 8289024
TI  - Stereochemical structure characterization of dental gutta-percha.
AB  - Natural gutta-percha is well known for its mechanical properties which derive
      from its particular stereochemical 1-4 trans structure. The gutta-percha
      contained in the various commercially available points is made of natural gutta
      percha which has undergone a heating process to allow inclusion of the other
      elements found in its composition, especially a nonspecified coloring agent. The
      purpose of this study was to confirm that the stereochemical 1-4 trans structure
      contained in commercial points is identical to that of natural gutta-percha and
      that it has not been altered by the heating process inherent to its fabrication.
      Furthermore, we wanted to identify the coloring agent also included in its
      composition. Samples of commercial gutta-percha points were studied using nuclear
      magnetic resonance spectral analysis and compared with that of natural gutta
      percha. Our results show that both natural and commercial gutta-percha mainly
      have a 1-4 trans stereochemical structure and that the coloring agent is
      erythrosin.

PMID- 8289025
TI  - Effect of variable doses of dexamethasone on posttreatment endodontic pain.
AB  - One hundred six patients with pretreatment pain presenting for endodontic
      treatment participated in a controlled double blind study. After root canal
      therapy, the patients were given an intraoral intramuscular injection of either a
      saline placebo or various dosages of dexamethasone. Posttreatment pain incidence
      and severity were evaluated at 4, 8, 24, 48, and 72 h. Injection of the various
      dosages of dexamethasone, taken as a group, was shown to significantly reduce the
      severity of pain at 4 and 8 h, and 0.07 to 0.09 mg/kg dosage alone significantly
      reduced pain at 8 h. Patients who received dexamethasone took significantly fewer
      posttreatment pain medications than those who received the placebo. Although
      there was a trend toward a reduction in the incidence of posttreatment pain for
      patients who received dexamethasone, the difference was not statistically
      significant.

PMID- 8289026
TI  - Apical sealing ability of metal versus plastic carrier Thermafil obturators.
AB  - Sixty straight maxillary canines, 40 straight mandibular incisors, and 40 curved
      mesial canals of 27 mandibular molars were instrumented and randomly assigned to
      one of seven groups of 20 canals. Experimental groups were obturated with metal
      or plastic carrier Thermafil obturators. Control groups were obturated using the
      lateral condensation technique. An additional group of 20 unobturated curved
      molar canals served as positive controls. Kerr Pulp Canal Sealer was used in all
      obturation groups. The presence or absence of apical extrusion of gutta-percha
      was recorded. Teeth were suspended in black India ink for 2 wk, cleared, and then
      examined under a dissecting microscope at x20 magnification. No leakage was found
      in any of the obturated canals, whereas unobturated controls showed total dye
      penetration. Plastic carrier Thermafil and metal carrier Thermafil groups
      produced a significantly greater incidence of apical extrusion of gutta-percha
      compared with lateral condensation groups (p < 0.001). Extrusion for Thermafil
      groups occurred significantly more frequently in straight compared with curved
      canals (p = 0.002). The Thermafil groups showed a higher frequency of filled
      lateral and accessory canals than in the lateral condensation group; however,
      this was statistically insignificant (p = 0.48).

PMID- 8289027
TI  - Effective shelf-life of prepared sodium hypochlorite solution.
AB  - Although the tissue solvent and bactericidal properties of sodium hypochlorite
      are well known, the effective shelf-life of prepared sodium hypochlorite
      solutions is not known. The stability of sodium hypochlorite is adversely
      affected by exposure to high temperature, light, air, and the presence of organic
      and inorganic contaminants. The purpose of this study was to investigate the
      variables of storage conditions and time on the tissue-dissolving capacity of
      three different concentrations of sodium hypochlorite. Fresh frozen human
      umbilical cord was used as the tissue sample for this experiment. Tissue samples
      were dissolved at time intervals ranging from 1 day to 10 wk in 5.25%, 2.62%, and
      1.0% solutions of sodium hypochlorite. The tissue-dissolving ability of 5.25%
      sodium hypochlorite remains stable for at least 10 wk. The tissue-dissolving
      ability of 2.62% and 1.0% sodium hypochlorite remains relatively stable for 1 wk
      after mixing, then exhibits a significant decrease in tissue-dissolving ability
      at 2 wk and beyond.

PMID- 8289028
TI  - Drying periapical films: simplified chairside technique.
AB  - A technique is presented for constructing a chairside radiograph dryer to be used
      after manual developing of films in the operatory. It is of simple construction
      using household items and common dental laboratory materials.

PMID- 8289029
TI  - Patient hotels.

PMID- 8289030
TI  - Cancer registration: its uses in research, and confidentiality in the EC.

PMID- 8289031
TI  - Housing in early life and later mortality.
AB  - STUDY OBJECTIVES: The aim was to examine the influence of domestic crowding and
      household amenities in early life on later mortality from all causes and
      specifically from stomach cancer, chronic obstructive pulmonary disease, and
      rheumatic heart disease. DESIGN: This was a retrospective cohort study of people
      whose houses had been surveyed in 1936 and whose household size was known from
      the 1939 census. Subjects were followed through the National Health Service
      Central Register from 1951 to 1989. SETTING: The housing survey had been carried
      out in the midland town of Chesterfield. SUBJECTS: Subjects comprised 8138 men
      and women born after 1900. RESULTS: A total of 2929 deaths were observed during
      the follow up period. All causes mortality in the full cohort was not
      consistently related to any of the housing variables examined, but among subjects
      who were still children at the time of the housing survey, death rates were
      higher in those whose houses were crowded or lacked a hot water tap. No
      associations could be shown between stomach cancer and domestic crowding or food
      storage facilities; chronic obstructive pulmonary disease and domestic crowding
      or use of gas for cooking; or rheumatic heart disease and domestic crowding.
      There were few deaths from these causes, however, in subjects who were children
      at the time of housing survey. CONCLUSIONS: The findings suggest that the housing
      of young adults in Chesterfield during the 1930s had little effect on their later
      mortality. Further follow up of the cohort is needed before firm conclusions can
      be drawn about the influence of housing at younger ages.

PMID- 8289032
TI  - Disability in young adults: the role of injuries.
AB  - STUDY OBJECTIVES: To describe the prevalence of disability in young adults and
      estimate the contribution that injuries make to disability. DESIGN: The study
      uses data from a British longitudinal survey, the National Child Development
      Study (1958 cohort). Disability at age 23 was ascertained from three questions
      asked in an interview with cohort members in 1981: these related to longstanding
      illness that limits activity, permanent disability following an accident after
      age 16, and registered disability. Lower and upper estimates of the contribution
      of injuries to disability were derived from ICD-9 codes allocated to the
      disabilities. SUBJECTS: These comprised 12,537 subjects, representing 76% of the
      target population, cohort members still alive and resident in Britain in 1981.
      MAIN RESULTS: Prevalence of disability according to the three definitions was: 46
      per 1000 with limiting longstanding illness; 28 per 1000 with a permanent
      accident related disability of onset after age 16; and 10 per 1000 registered
      disabled. Combining all three definitions, the overall prevalence of disability
      was 68 per 1000, with men reporting more disability than women. It was estimated
      that an injury caused the disability for 16.7% of subjects, at the lower
      estimate, and 26.0% at the upper estimate (23.1% to 32.1% for men and 8.6% to
      18.4% for women). For limiting longstanding illness of onset after 16, between
      33.5% and 47.8% was due to an injury. Road accidents caused 31% of permanent
      accident related disability. Over one half of men and nearly three quarters of
      women reporting permanent accident related disability had not been admitted to
      hospital for their injury. CONCLUSIONS: Injuries are an important cause of
      disability in young adults, particularly injuries resulting from accidents after
      age 16. Accident prevention in the 16-24 group has the potential to reduce the
      prevalence of disability substantially.

PMID- 8289033
TI  - Varicose veins in a Finnish population aged 40-60.
AB  - STUDY OBJECTIVE: To assess the prevalence and the extent of treatment of varicose
      veins in a Finnish population. DESIGN: A prevalence study in a defined cohort was
      performed by using a mailed questionnaire. The method's validity was tested in a
      random sample of 166 individuals who were studied clinically. SUBJECTS: In 1989 a
      questionnaire was mailed to every resident born in 1929, 1939, and 1949 who was
      living in Tampere, the second largest town in Finland. The eligible population
      comprised 3284 men and 3590 women. MEASUREMENTS AND MAIN RESULTS: The response
      rate was 75% in men and 86% in women. Both the sensitivity and specificity of the
      self assessed diagnosis were 0.92. The life time prevalence of varicose veins was
      18% for men and 32% for women, with an increasing prevalence in relation to age.
      Twenty five per cent of the men and 41% of the women who reported varicose veins
      had received treatment. CONCLUSIONS: Self reporting of varicose veins by mailed
      questionnaire was a relatively valid method. The prevalence of varicose veins was
      high in the population studied, and the disease is more common in women than men.
      Moreover, the prevalence increased with age. The results are comparable with
      other western populations. Preventive methods are needed because treatment alone
      seems to be inadequate in the control of varicose veins.

PMID- 8289034
TI  - Another British disease? A recent increase in the prevalence of psychiatric
      morbidity.
AB  - AIMS AND OBJECTIVE: To examine trends in the prevalence of psychiatric morbidity
      in Britain between 1977 and 1985. DESIGN: Secondary analysis of two cross
      sectional population based surveys. SETTING: The first survey was conducted in
      1977 in West London and the second in 1984-85 throughout Great Britain.
      PARTICIPANTS: Members of the public randomly selected from the electoral
      register. MEASUREMENTS AND MAIN RESULTS: The main outcome was the prevalence of
      psychiatric morbidity assessed using the General Health Questionnaire, a self
      administered measure of neurotic symptoms. There was an increase of at least 8%
      (95% confidence interval 6.6, 9.8) in the prevalence of psychiatric morbidity
      between the times of the two surveys and this difference persisted after
      adjustment for any changes in the sex, age, employment status, marital status,
      social class, and housing tenancy between the two samples. When the analysis was
      restricted to the Greater London respondents of the Health and Lifestyle Survey a
      larger increase in psychiatric morbidity was seen. CONCLUSIONS: It is likely that
      there was an increase in the prevalence of psychiatric morbidity in Great Britain
      between these two surveys. Psychiatric morbidity is a public health problem of
      some importance and the causes of this increase require further study.

PMID- 8289035
TI  - Changing seasonality of birth--a possible environmental effect.
AB  - STUDY OBJECTIVE: Seasonality of birth was examined to determine whether this has
      changed over the last half century. DESIGN: Time-series analysis was carried out
      on retrospective data, both for the full 50 year period and for the five decades
      within that period. Although the primary objective was to investigate seasonality
      by fitting an appropriate model and examining changes over the period studied,
      non-seasonal trends were also examined. SETTING: Data by month were obtained from
      the Registrar General on all births in Scotland during the years 1938-87.
      SUBJECTS: There was a total of 4,325,000 births in the 50 years examined.
      MEASUREMENTS AND MAIN RESULTS: There are two peaks to the seasonality rhythm--one
      wide, in spring/early summer and one narrow, in October. Cosinor analysis,
      modified to allow for the second peak, was used to fit a sine curve model.
      Analysis of variance showed that this was adequate and established the
      significance of both peaks. The main peak of seasonal excess rose to a maximum in
      1948-57, and thereafter declined by two thirds. While the position of the main
      peak moved forward two months over the 50 years, the October peak remained
      unchanged until the final decade, when it rose slightly; thus its relative
      importance increased steadily from 1948 onwards. CONCLUSIONS: The changing
      biological rhythm may be related to alterations in the climate and environment or
      to social differences.

PMID- 8289036
TI  - Enhancing appropriateness of acute bed use: role of the patient hotel.
AB  - OBJECTIVE: This study aimed to assess the appropriateness of bed use by
      determining patients' suitability for patient hotel accommodation and day
      treatment and by examining timeliness of discharge, and to assess patient and
      staff views about patient hotels. DESIGN: Patients were assessed by a doctor and
      nurse in terms of an agreed case definition for patient hotel use. Patient
      suitability was validated and patient acceptability measured by semi-structured
      interviews with a random sample of patients judged suitable for hotel
      accommodation. All senior medical and nursing staff completed a further
      questionnaire. SETTING: The study took place at University Hospital of Wales,
      Cardiff (856 beds), and all specialties, except intensive care wards,
      participated. SUBJECTS: Patients occupying a total of 3972 bed days, accumulated
      over seven randomly chosen census days, were studied. RESULTS: Data were
      available for 88% of eligible inpatients. Ten per cent (405 of 3972) of patients
      were judged suitable for a patient hotel. Specialties indicating major use were
      obstetrics and gynaecology, general surgery, and general and geriatric medicine.
      Sixty three per cent (254 of 405) of these subjects required low level
      investigation or treatment. Preoperative and postoperative and antenatal patients
      were often suitable also. Three per cent (119 of 3972, 95% confidence interval
      2.5, 3.6%) of inpatients were judged suitable for day treatment/investigation.
      Seventy nine per cent (291 of 369) of patients suitable for discharge were
      discharged on the same or the next day. The patient hotel idea was acceptable to
      58 of 68 (85%) randomly selected patients and to 84 of 93 (90%) staff.
      CONCLUSIONS: With allowance for non-response, our study indicates that a general
      hospital of this size generates the need (inpatients, relatives, and ward
      attenders) for a mean of 72 patient hotel beds. There is also residual scope for
      increasing day treatment/investigation and for releasing beds by speeding
      discharge. The patient hotel idea is highly acceptable to both patients and staff
      and should be widely considered as a means of making patient care more efficient.

PMID- 8289037
TI  - Can a surgical treatment centre reduce waiting lists? Results of a natural
      experiment.
AB  - STUDY OBJECTIVE: To determine the effectiveness of the Welsh general surgery
      (hernia and varicose veins) treatment centre established as part of the NHS
      reforms, in terms of its impact upon throughput and waiting lists. DESIGN: This
      was a natural experiment with two control groups--other surgical specialties
      without treatment centre provision, and general surgery in districts that made
      only minor use of the facility. SETTING: General Surgery Treatment Centre,
      Bridgend General Hospital. SUBJECTS: All patients referred between 1 April 1990
      and 31 March 1991. MEASUREMENTS AND MAIN RESULTS: Main outcome measures were
      throughput for hernia and varicose vein operations, non-urgent inpatient waiting
      list lengths before and after the opening of the centre and patient satisfaction.
      Altogether 1097 patients were referred during the year. Of these, 160 (15%) did
      not attend outpatient assessment and 79 (8%) of those who did were unsuitable for
      surgery. A total of 750 operations were performed--448 (60%) for varicose veins
      and 261 (35%) hernia repairs. Among the residents of the four main districts
      using the centre (with valid data available), there was a significant increase in
      the total number of varicose vein operations performed but no significant
      increase in hernia repairs. In the six districts that made major use of the
      centre, general surgery waiting lists for non-urgent cases fell significantly (p
      < 0.0001) while those for ear, nose, and throat showed no significant change and
      gynaecology lists lengthened significantly (p < 0.0001). In the three districts
      that made minor use of the centre general surgery waiting lists showed no change.
      CONCLUSIONS: Relations between inputs and waiting lists are often unpredictable,
      but after controlling for confounding trends there is sound evidence that such a
      centre provides an acceptable and effective approach to the waiting list problem.

PMID- 8289038
TI  - Loss of quality adjusted days as a trial endpoint: effect of early thrombolytic
      treatment in suspected myocardial infarction. Grampion Region Early Anistreplase
      Trial (GREAT).
AB  - STUDY OBJECTIVES: (1) To measure the quality of life and the loss of quality
      adjusted days (QADS) after suspected acute myocardial infarction in patients who
      received thrombolytic treatment either at home or in hospital. (2) To compare the
      loss of QADS as a trial endpoint with the conventional endpoints of mortality and
      Q-wave infarction. DESIGN: Randomised double blind parallel group trial of
      anistreplase (30 U given intravenously) and placebo given either at home or in
      hospital. SETTING: Rural practices in Grampian admitting patients to teaching
      hospitals in Aberdeen. PATIENTS: A total of 311 patients with suspected acute
      myocardial infarction and no contraindications to thrombolytic treatment seen at
      home within four hours of the onset of symptoms. MEASUREMENTS AND MAIN RESULTS:
      Loss of quality adjusted days (QADS) in the first 100 days after suspected
      myocardial infarction (365 QADS = 1 QALY) was the main outcome measure. Compared
      with later administration in hospital, anistreplase at home resulted in a
      relative reduction of mortality of 49% (95% confidence interval 3.95%, 2p =
      0.04), and a relative reduction of 26% in the proportion of survivors with
      infarction who had Q-waves (95% CI 7.44%, 2p = 0.007). During the 100 day follow
      up, the median loss of QADS was 25 for all patients. This loss was significantly
      greater in those who died than in survivors (65 v 18, 2p < 0.001), and in
      survivors with infarction than in survivors without infarction (26 v 13, 2p <
      0.01). However, there was no significant difference in loss of QADS in those with
      infarction with or without Q-waves (29 v 21, NS), and the median loss of QADS was
      not significantly different in those who had thrombolytic treatment at home or in
      hospital (median difference 0, 95% CI -5, +4 QADS). CONCLUSIONS: Loss of QADS had
      two serious limitations as an outcome measure: it was less sensitive than
      mortality and it failed to reflect physiological benefit. Palliative treatment
      with no physiological effect would have resulted in a greater gain in QADS (or
      QALYs) than did early thrombolytic treatment. Extreme caution is required in
      accepting a gain in QALYs as a valid outcome measure for health care.

PMID- 8289039
TI  - Pattern of ophthalmological accidents and emergencies presenting to hospitals.
AB  - STUDY OBJECTIVE: To investigate the numbers and characteristics of patients with
      ophthalmological accidents and emergencies presenting to hospitals. DESIGN:
      Prospective survey over eight weeks. SETTING: Two general and one ophthalmic
      accident and emergency departments, two general outpatient departments, and an
      eye hospital ward consulting room (all in two teaching hospitals) in Newcastle
      upon Tyne. MEASUREMENTS AND MAIN RESULTS: Consultation numbers by age, sex,
      health district of residence, source of referral, diagnosis, and disposal were
      determined. An average of 37 ophthalmological emergency patients were seen daily.
      The all cause consultation rate per 1000 population for Newcastle residents was
      2.64 (17.2 per year); for injuries it was 1.10 (7.2 per year) and for
      inflammations the rate was 0.91 (5.9 per year). Consultation rates per 1000 were
      3.5 for males and 1.8 for females, the excess being explained by the higher risk
      of injury to men. Most patients were self-referred (58%), consulted during office
      hours (79.6%), were attended by senior house officers working alone (83.9%), and
      were asked to return for follow up (66.1%). Patients in an accident and emergency
      department seldom saw a consultant in their initial management. The diagnoses of
      patients from outside Newcastle were little different from those who lived within
      the city. The 10 commonest problems accounted for 68% of all cases. Injuries were
      the commonest problem (40.9% of all diagnoses). CONCLUSION: Ophthalmological
      accident and emergencies are an important component of an accident and emergency
      department workload. These patients are usually seen by junior doctors, some
      untrained in ophthalmology. The wide range of presenting problems poses a
      challenge for training and the organisation of effective referral chains, while
      the gender difference in injury rates points to the potential for prevention.

PMID- 8289040
TI  - Incapacity for work in elective orthopaedic surgery: a study of occurrence and
      the probability of returning to work after treatment.
AB  - STUDY OBJECTIVE: The extent to which patients undergoing elective surgery for
      orthopaedic disorders were incapacitated for work while they were on the waiting
      list and whether they were able to return to work after surgery were studied.
      DESIGN: This was a prospective cohort study of patients admitted to hospital for
      elective orthopaedic surgery. Main outcome measures were occurrence of sickness
      certification during the waiting time, and whether those incapacitated for work
      at the time of surgery returned to work during the first year after treatment.
      Multivariate logistic regression was used to estimate adjusted odds ratios for
      factors influencing return to work. SETTING: Orthopaedic department in charge of
      all elective orthopaedic surgery in a population of 197,354 persons in central
      Norway. SUBJECTS: All 2803 patients admitted to hospital for chronic orthopaedic
      disorders in the defined population between 1 September 1988 and 31 August 1990
      were included in the study. MAIN RESULTS: Of the 1333 patients who were employed,
      42% had been certified sick due to the orthopaedic disorder for some period of
      the waiting time. Sickness benefits from the national insurance scheme (paid from
      the 15th day of sickness certification) had been received by 33% and were
      received by 29% at the time of surgery. Of 380 patients incapacitated for work at
      the time of surgery, 53% returned to work within the first year after surgery.
      Using those treated within one month of being placed on the waiting list as the
      reference group, the adjusted odds ratios for not returning to work during the
      first year after surgery were 9.2 (p < 0.0001) for those who waited more than a
      year for surgery, 6.2 (p = 0.002) for those waiting nine to 12 months, and 4.9 (p
      = 0.02) for those waiting for six to nine months. CONCLUSIONS: A high proportion
      of these patients were incapacitated for work, 53% of those incapacitated
      returned to work within the first year after surgery. The probability of
      returning to work after surgery is strongly influenced by the length of time on
      the waiting list. Waiting for more than one year, compared with immediate
      treatment, was associated with an adjusted odds ratio of 9.2 for not returning to
      work.

PMID- 8289041
TI  - Wilderness medicine.

PMID- 8289042
TI  - Cervicography.

PMID- 8289043
TI  - Urinary frequency in children.

PMID- 8289044
TI  - Smokeless tobacco.

PMID- 8289045
TI  - Military family practitioners join the ranks of The Journal of Family Practice.

PMID- 8289046
TI  - Prevalence of hypertension, dyslipidemia, and dyslipidemic hypertension.
AB  - BACKGROUND: It has been proposed that dyslipidemic hypertension is part of a
      distinct metabolic syndrome related to insulin resistance. This paper describes
      the prevalence and cross-sectional relations of dyslipidemic hypertension in a
      population-based sample of men and women. METHODS: In two southeastern New
      England communities, 11,199 randomly selected participants were evaluated as part
      of a cross-sectional surveillance program of coronary heart disease risk factors
      between 1981 and 1990. RESULTS: The frequency of dyslipidemia was 38% and of
      hypertension was 26.5%; the conjoint frequency (dyslipidemic hypertension) was
      15.0%, which is 1.49 times the expected value if the two diseases were
      independent P < .05). Using a discrete multivariate model, dyslipidemia and
      hypertension were associated with sex, obesity, and diabetes mellitus. The excess
      association of dyslipidemic hypertension, compared with individual effects of
      dyslipidemia and hypertension, was not related to these factors. CONCLUSIONS:
      This study suggests that dyslipidemic hypertension is common but may not be a
      unique entity associated with a distinct metabolic syndrome.

PMID- 8289047
TI  - Factors associated with appointment keeping in a family practice residency
      clinic.
AB  - BACKGROUND: Failure to keep an appointment not only affects the patient's health
      care, but also has an impact on the effectiveness and productivity of the medical
      facility. This study explored patient demographic factors associated with
      appointment keeping. METHODS: In a Midwestern, urban family practice residency
      clinic serving 2500 patient visits each month, data were obtained from the
      computer scheduling system and chart audits for 4669 patients who kept or missed
      7283 physician appointments between April and June 1991. Independent variables
      studied were age, race and ethnicity, type of health insurance, marital status,
      sex, patient status, day and time of appointment, medical reason for the visit,
      and geographic proximity to the clinic. RESULTS: The kept-appointment rate for
      this study was 73.9%. Appointment keeping was associated with age, race and
      ethnicity, type of health insurance, the day of the appointment, the medical
      reason for the visit, and geographic proximity to the clinic. Rates of
      appointment keeping were higher for patients who were older, who were Asian or
      white, who had private or managed care insurance, who had longer distances to
      travel to the clinic, and those who had appointments scheduled for the day on
      which they contacted the clinic. CONCLUSIONS: Several identifiable factors
      significantly affect whether a patient will keep a clinic appointment. Our
      findings should be considered in program changes in appointment scheduling and
      follow-up methods for noncompliant patients.

PMID- 8289048
TI  - Swimming and grommets.
AB  - BACKGROUND: Traditionally, children with tympanostomy ventilating tubes, or
      grommets, were advised that water should not enter their ears in order to prevent
      ear infections. This group of children has been considered somewhat handicapped
      regarding swimming. We conducted a prospective study to determine if there is a
      relation between suppurative otitis media and surface swimming in children with
      grommets. METHODS: Forty-two children with tympanostomy ventilating tubes were
      included in this study. Of the 42 children, 22 were swimmers and 20 were
      nonswimmers, who served as the control group. The age range was 3 to 12 years,
      and there was no difference in the age distribution between the groups. Surface
      swimming was allowed without earplugs or a bathing cap, although it was mandatory
      to use polymyxin B-neomycin-hydrocortisone eardrops at bedtime on the day of
      swimming. No diving was allowed. RESULTS: Three of 22 swimmers and 2 of 20
      nonswimmers developed otorrhea. In 4 of the 5 children, the otorrhea was followed
      by an upper respiratory tract infection. In all cases, a bacterial culture
      revealed Pseudomonas. The ear drainage was easily controlled with local otic
      treatment in all the patients. CONCLUSIONS: Taking into consideration the
      possible risks of infection and bearing in mind the value and joy of swimming to
      children and parents, families should be reassured that surface swimming does not
      increase the risk of infection in children with tympanostomy tubes.

PMID- 8289049
TI  - CD8+ lymphocyte counts and the risk of death in advanced HIV infection.
AB  - BACKGROUND: Mortality related to human immunodeficiency virus (HIV) infection
      occurs predominantly in patients with CD4+ lymphocyte counts of less than 50
      cells/mm3. We followed 133 HIV-infected patients with enrollment CD4 counts of
      less than 50 cells/mm3 to determine if the risk of death during a 1-year period
      could be predicted by a single enrollment CD8+ lymphocyte count. METHODS:
      Enrollment data including age, sex, T-cell subset counts, p24 antigen status,
      antiretroviral use, and preexisting HIV-related illnesses were collected on a
      cohort of 133 consecutive patients with enrollment CD4 counts of less than 50
      cells/mm3. The cohort was followed for 1 year, and survival data were analyzed in
      relation to enrollment variables. RESULTS: The mean enrollment CD8 count of those
      patients alive at 1 year was 600 cells/mm3, compared with a mean enrollment CD8
      count of only 370 cells/mm3 in patients who had died prior to 1 year (P < .001).
      For every 100-cell decline in the enrollment CD8 count, the risk of death
      increased by 16% (95% confidence interval [CI], 5% to 22%), independent of other
      enrollment variables, including CD4 counts and p24 antigen status. A significant
      CD8 count warning level of 415 cells/mm3, irrespective of the presence of other
      enrollment variables, was associated with death within 1 year. The Kaplan-Meier
      estimated chance of death within 1 year was 54% (95% CI, 42% to 66%) for patients
      with CD8 counts of less than 415 cells/mm3 compared with only 25% (95% CI, 14% to
      36%) for patients with CD8 counts greater than 415 cells/mm3. CONCLUSIONS: This
      study finds that a single CD8 count has important prognostic significance in
      patients with advanced HIV infection and suggests that potential therapies to
      enhance CD8 counts might be beneficial to patients with advanced HIV infection.

PMID- 8289050
TI  - A comparison of uterine cervical cytology and biopsy results: indications and
      outcomes for colposcopy.
AB  - BACKGROUND: There is some debate in the literature over the proper approach to
      the patient with a mildly abnormal cervical cytologic finding. One current
      approach for handling low-grade cytologic abnormalities is to perform colposcopy
      and biopsy if atypia, human papillomavirus (HPV) changes, or mild dysplasia is
      noted on cytologic examination. If a Papanicolaou (Pap) smear shows inflammation
      without atypia, the test is repeated after 3 months, and if inflammation does not
      clear, colposcopy is performed. This study was undertaken to determine whether
      the above recommendations are appropriate. METHODS: In a 1-year period, 125
      patients underwent colposcopy and biopsy. Results were reviewed and compared.
      RESULTS: Of 47 patients with smears showing human papillomavirus (HPV) changes,
      68% had a higher grade abnormality (dysplasia) on biopsy; 15% had moderate or
      severe dysplasia. Of eight patients with atypia, 63% had dysplasia on biopsy. Of
      41 patients with mild dysplasia on Pap smear, 37% had moderate dysplasia or
      higher grade disease on biopsy. Of nine patients with persistent inflammation on
      cytologic examination, biopsy showed 56% with inflammation, 33% with mild
      dysplasia, and 11% normal. CONCLUSIONS: Patients who presented with minimal Pap
      smear abnormalities such as HPV changes or atypia are likely to have a worse
      histologic diagnosis, with approximately two thirds showing dysplasia. Patients
      with persistent inflammation are less likely to have dysplasia. The results
      support our aggressive approach toward minimally abnormal smears and our
      consideration of inflammation without atypia as a separate and lower risk
      category.

PMID- 8289051
TI  - Patient attitudes toward physician treatment of obesity.
AB  - BACKGROUND: Family physicians are frequently faced with the problem of caring for
      overweight patients since 30% to 40% of American adults are overweight and 10%
      are obese. The traditional approach of physicians treating obese patients, which
      includes diet instruction, dietitian referral, and supportive therapy, has
      demonstrated little success. METHODS: A focus group of obese patients was formed
      to discuss weight-loss therapy from a patient viewpoint. Three sessions were
      completed, one each for patients' feelings and life experiences, exercise, and
      eating habits. The traditional medical approach to weight-loss therapy was
      discussed. RESULTS: All participants reported having failed physicians' attempts
      to aid them in weight loss. Similarly, all related negative life experiences, job
      discrimination, and derogatory remarks that they attributed to their weight.
      Participants were not supportive of physicians' traditional approach to aiding
      patients with weight loss. CONCLUSIONS: The results suggest that the traditional
      approach to treating patients' excessive weight is not helpful from the patient
      viewpoint. Study participants were more supportive of a group approach to the
      treatment of obesity that would include group exercise and modification of
      currently used foods rather than new low-calorie recipes. The issues of
      transportation and child care must be addressed by weight-loss programs.

PMID- 8289052
TI  - New antidepressants and the treatment of depression.
AB  - Depression is a common and significant health problem associated with impairment
      in a patient's ability to function. The development of new antidepressant
      medications represents progress in its treatment. These new agents work through
      the selective blockade of the reuptake of serotonin into the presynaptic neuron,
      thereby increasing the availability of this neurotransmitter at the synaptic
      cleft and enhancing its effectiveness. While no more effective than traditional
      tricyclic antidepressant drugs, the new agents are generally safer than
      traditional medications used to treat depression: they are well tolerated and, in
      case of overdose, less harmful than tricyclic antidepressants.

PMID- 8289053
TI  - An etiologic approach to management of duodenal and gastric ulcers.
AB  - With rare exception, peptic ulcers can now be classified as either Helicobacter
      pylori-related, induced by nonsteroidal anti-inflammatory drugs (NSAIDs), or
      related to Zollinger-Ellison syndrome. Helicobacter pylori-related ulcers can be
      treated by eradication of H pylori or by traditional therapies, including
      antisecretory drugs or sucralfate. Successful eradication of H pylori requires
      compliance with a multidrug regimen. Therefore, candidates should demonstrate
      substantial motivation. In general, the greater the degree of ulcer recurrence or
      resistance, the stronger the indication for H pylori eradication. Sucralfate is
      effective in healing H pylori-related duodenal ulcers, and H2 receptor
      antagonists heal H pylori-related duodenal and gastric ulcers. Omeprazole
      provides faster healing of H pylori-related ulcers, and is particularly useful in
      treating large gastric ulcers. Dyspepsia induced by NSAIDs and NSAID-related
      endoscopic erosions are managed by stopping NSAID use or reducing the dosage;
      administering NSAIDs with meals; and administering H2 receptor antagonists in
      full split-doses. NSAID-induced duodenal ulcers and small gastric ulcers can be
      healed with full split-doses of H2 receptor antagonists, even while the NSAID is
      continued. Large (> 5 mm) NSAID-induced gastric ulcers are most efficiently
      treated with omeprazole, particularly if the patient continues to take the NSAID.

PMID- 8289054
TI  - 'Fried chicken' medicine: the business of primary care.
AB  - The current environment of pressures for health care reform have created a
      renewed interest in primary health care delivery. In most health care reform
      scenarios, family physicians and other primary care doctors are the case managers
      for all health care delivery. At the same time, there are intense activities from
      investment banking firms, insurance companies, hospitals, and home health
      companies, directed toward the purchase of primary care practices and organizing
      primary care delivery systems. These organizations seek to profit either from
      ancillary services generated by primary care or from capitation for a population
      of managed-care patients. Based on personal employment experiences with a for
      profit hospital company, the author illustrates the difficulty in developing and
      managing primary care as a business and the inevitable conflict between
      management and primary care physicians. The article has detailed advice for
      family physicians to aid them in carefully examining organizational culture,
      financial structuring, physician relations, and operational aspects of any for
      profit or hospital primary care system before deciding to become part of it.

PMID- 8289055
TI  - Cervical carcinoma in situ undetected by Papanicolaou smear but identified by
      cervicography. A case report.
AB  - The following case report demonstrates the clinical use of cervicography as an
      adjunct test to identify premalignant or malignant cervical disease. An
      asymptomatic woman seeking routine health maintenance care was screened by serial
      Papanicolaou (Pap) smears and cervicography. The interval Pap smears were
      interpreted as satisfactory and within normal limits; however, the cervigrams
      were interpreted sequentially as atypical and positive. A subsequent cervical
      biopsy revealed carcinoma in situ. Cervicography, as an adjunct test, enhanced
      cervical cytologic screening of a woman considered to be at high risk because of
      a prior history of genital human papillomavirus infection.

PMID- 8289056
TI  - Closet hypoglycemia.
AB  - An elderly nondiabetic woman was found stuporous and unresponsive at home. In the
      emergency department, testing revealed that she had a serum glucose of 40 mg/dL
      (2.2 mmol/L). No underlying metabolic cause could be determined. An inspection of
      her medications disclosed a professional medication sample bottle labeled as
      containing a nonsteroidal anti-inflammatory drug (NSAID) that actually contained
      chlorpropamide tablets. Drugs, notably sulfonylureas, must be considered as a
      possible cause of unexplained severe hypoglycemia.

PMID- 8289057
TI  - Thomas Sydenham, MD (1624-1689): the father of clinical observation.

PMID- 8289058
TI  - Retraction notice.

PMID- 8289059
TI  - Isolation of echinocystic acid-3-O-sulfate, a new triterpene, from Tetrapleura
      tetraptera, and evaluation of the mutagenic potential of molluscicidal extracts
      and isolates.
AB  - A known triterpene glycoside, 3-O-[beta-D-glucopyranosyl-(1"-6')-2'-acetamido-2'
      deoxy-beta-D-gluco pyranosyl]olean-12-en-28-oic acid [3], and new sulfated
      triterpene, echinocystic acid-3-O-sodium sulfate [4], have been isolated from the
      stem bark of Tetrapleura tetraptera. Compound 3 was 100% lethal to Biomphalaria
      glabrata at 20 ppm, while 4 was not molluscicidal at the same concentration. In a
      forward mutation assay utilizing Salmonella typhimurium strain TM677, T.
      tetraptera stem bark extracts were found to be mutagenic in the absence of a
      metabolic activating system (S-9). An MeOH extract of the fruit exhibited weak
      mutagenic activity only in the presence of S-9. The stem bark isolates, which
      included aridanin [1], 3-O-(2'-acetamido-2'-deoxy-beta-D
      glucopyranosyl)echinocystic acid [2], and compounds 3 and 4, were not mutagenic
      either with or without metabolic activation.

PMID- 8289060
TI  - Antimicrobial compounds from Petalostemum purpureum.
AB  - EtOH extracts of Petalostemum purpureum demonstrated antimicrobial activity
      against bacteria and fungi. Bioassay-directed fractionation led to the isolation
      of petalostemumol [1] as the active constituent. Its structure was determined by
      a single crystal X-ray diffraction analysis. A minor component designated
      petalostemumol G [3] is believed to be an artifact of the isolation procedure.
      Its structure was confirmed by a single crystal X-ray analysis of its
      pentamethylether 2. A number of derivatives of 1 and 3, including the Me- and
      benzylethers and acetates, were prepared.

PMID- 8289061
TI  - Two new modified trichothecenes from Fusarium sporotrichioides.
AB  - Two new modified trichothecenes, 2-deoxy-11-epi-3 alpha-hydroxysambucoin [1] and
      2-deoxy-11-epi-12-acetyl-3 alpha-hydroxysambucoin [2], were isolated from
      Fusarium sporotrichioides culture. This is the first report of modified
      trichothecenes where the two six-membered rings are cis-fused. Structures were
      elucidated using gc-ms, nmr, X-ray crystallography, and other spectroscopic
      techniques. Compounds 1 and 2 were screened for relative cytotoxicity in cultured
      baby hamster kidney (BHK-21) cells and found to be non-toxic.

PMID- 8289062
TI  - Triterpene glycosides from the roots of Dipsacus asper.
AB  - The roots of Dipsacus asper have yielded two new triterpenoid saponins, dipsacus
      saponins B [1] and C [2], which have been characterized by chemical and spectral
      means and spectral means as hederagenin-3-O-beta-D-glucopyranosyl-(1-->4)-[alpha
      L-rhamnopy ran osyl- (1-->6)]-beta-D-glucopyranosyl-(1-->3)-alpha-L
      rhamnopyranosyl-(1-->2)-a lpha- L-arabinopyranoside [1] and hederagenin-3-O-beta
      D-xylopyranosyl-(1-->4)- beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-
      >3)-[alpha-L- rhamnopyranosyl-(1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-
      arabinopyranoside [2].

PMID- 8289063
TI  - Zaragozic acids D and D2: potent inhibitors of squalene synthase and of Ras
      farnesyl-protein transferase.
AB  - Two new zaragozic acids, D and D2, have been isolated from the keratinophilic
      fungus Amauroascus niger. Zaragozic acids D [4] and D2 [5] are related to the
      previously described zaragozic acids A [1], B [2], and C [3] and are potent
      inhibitors of squalene synthase. Furthermore, all the zaragozic acids (A, B, C,
      D, and D2) are also active against farnesyl transferase. Zaragozic acids D and D2
      inhibit farnesyl transferase with IC50 values of 100 nM, while zaragozic acids A
      and B are less potent.

PMID- 8289064
TI  - A new antimalarial quassinoid from Simaba guianensis.
AB  - Two antimalarial quassinoids, gutolactone [1] and simalikalactone D [2], have
      been characterized by bioactivity-directed fractionation from the bark of Simaba
      guianensis collected near Manaus, Brazil. Compound 2 was previously isolated from
      Simaba multiflora and Quassia africana and shown to be an active antimalarial in
      vitro. This is the first occurrence of 1. The structure of the novel quassinoid
      was established by spectral methods including 2D nmr spectroscopy.

PMID- 8289065
TI  - Isolation of the nickel-chlorin chelate tunichlorin from the South Pacific ocean
      sea hare Dolabella auricularia.
AB  - The Papua New Guinea shell-less mollusc Dolabella auricularia has been found to
      contain a series of green to blue-green chlorins. One of these compounds was
      found to be the nickel chelate tunichlorin [1] which was isolated previously only
      from the Caribbean tunicate Trididemnum solidum. Discovery of tunichlorin [1] in
      a sea hare suggests that its occurrence in algae-consuming marine animals may be
      more common than earlier realized, and it may have a role in electron transfer or
      other metabolic processes.

PMID- 8289066
TI  - Bisbenzylisoquinoline alkaloids from Cyclea barbata.
AB  - Continuing studies of the alkaloidal fraction from the roots of Cyclea barbata
      afforded two new bisbenzylisoquinoline alkaloids, namely, (-)-2'-norlimacine [1]
      and (+)-cycleabarbatine [2]. The known (+)-tetrandrine-2'-beta-N-oxide [3], for
      which the configuration of the N-oxide function is now assigned, was identified,
      as were (+)-berbamine, (-)-repandine, (+)-cycleanorine, (+)-daphnandrine, (-)
      curine, (+)-coclaurine, and (-)-N-methylcoclaurine.

PMID- 8289067
TI  - Aeruginol [2-(2'-hydroxyphenyl)-4-hydroxymethylthiazole], a new secondary
      metabolite from Pseudomonas aeruginosa.
AB  - The CHCl3 extract of Pseudomonas aeruginosa UI 29791 cultures afforded a novel
      fluorescent compound, aeruginol [1]. The structure of 1 was elucidated by
      spectroscopic methods, including uv, eims, cims, hreims, and 1H nmr. Aeruginol
      appears to be biosynthetically related to aeruginoic acid.

PMID- 8289068
TI  - Linusitamarin, a new phenylpropanoid glucoside from Linum usitatissimum.
AB  - From the defatted meal of flaxseed (Linum usitatissimum), a novel phenylpropanoid
      glucoside, linusitamarin [1], was isolated, along with a number of known
      compounds. The structure of 1 was determined by spectroscopic analysis.

PMID- 8289069
TI  - Biemnasterol, a new cytotoxic sterol with the rare 22,25-diene side chain,
      isolated from the marine sponge Biemna sp.
AB  - Biemnasterol [2], a new sterol with a 22,25-diene side chain possessing cytotoxic
      activity, has been isolated from the Okinawan marine sponge Biemna sp. and the
      structure elucidated on the basis of spectroscopic data and chemical means.

PMID- 8289070
TI  - 4'-O-methylstephavanine from Stephania abyssinica.

PMID- 8289071
TI  - Latent infection with the MS strain of herpes simplex virus type 2 in the mouse
      following intracerebral inoculation.
AB  - Intracerebral inoculation of the MS strain of herpes simplex virus type 2 (HSV-2)
      into mice causes an acute encephalitis associated with multifocal demyelination
      and necrotizing retinitis. We have studied the distribution of latent virus in
      mice that had recovered from the acute encephalitis. Four weeks or longer after
      inoculation, HSV-2 could be recovered from the trigeminal ganglia of all mice
      examined by co-culture of explants in roller tubes. The virus could not be
      recovered from explants of retina or brain stem. HSV-2 latency associated
      transcript (LAT) was readily detected in the trigeminal ganglia by reverse
      transcriptase-PCR more than 4 months after inoculation. LAT was also demonstrated
      in the brain but this required nested PCR for consistent detection. Both LAT and
      ICP0 mRNA were detected in brain tissue during the acute encephalitis but, unlike
      LAT, ICP0 mRNA could not be amplified from the trigeminal ganglia or brain beyond
      4 weeks after inoculation of the virus. In situ hybridisation with a double
      stranded DNA probe to the ICP0/LAT overlap region of HSV-2 revealed signal in
      trigeminal ganglion neurons and occasional cells in the brain stem. These
      findings indicate that HSV-2 introduced by intracerebral inoculation becomes
      latent in the trigeminal ganglia and that transcription of LAT also persists
      within the brain.

PMID- 8289072
TI  - Clinical signs of brain death simulated by Guillain-Barre syndrome.
AB  - A 58-year-old woman with relapsing acute Guillain-Barre syndrome separated by
      long asymptomatic intervals presented clinical symptoms resembling those of brain
      death. She remained in this situation for 15 days and recovered with amnesia for
      this period. The amnesia was not explained either by metabolic encephalopathy or
      by sedative drugs. This case stresses the importance of the precise etiologic
      diagnosis of severe brain disease and the isoelectric EEG in brain death.

PMID- 8289073
TI  - Mycobacterium tuberculosis polymerase chain reaction findings in
      neurosarcoidosis.

PMID- 8289074
TI  - Retraction.

PMID- 8289075
TI  - Widespread multiple system degeneration in a patient with familial amyotrophic
      lateral sclerosis.
AB  - We report a 57-year-old woman with familial amyotrophic lateral sclerosis (ALS)
      with posterior column involvement of 11 years duration. The patient had been on a
      respirator for more than 5 years before death. In addition to the well
      established pathology of this form of familial ALS, there were obvious
      degenerative changes in the brainstem tegmentum, including the reticular
      formation, cerebellar cortex, dentate and red nuclei, thalamus and mammillary
      body. Of great interest in this case was intracytoplasmic accumulation of
      neurofilaments in the remaining neurons in these areas, some of which, for
      instance, those in the oculomotor and abducens nuclei, still showed only minimal
      loss. This patient had survived considerably beyond the point of respiratory
      failure, which is the final stage in the natural history of the disease. We
      considered that in this patient the underlying degenerative process of the
      disease had become manifested in wider areas than recognized previously during
      the prolonged clinical course due to respiratory support. However, whether or not
      such widespread degeneration would occur in all patients with this disease who
      survive longer with the help of respiratory support awaits further studies.

PMID- 8289076
TI  - Cerebral blood flow and oxygen metabolism in progressive dementia associated with
      amyotrophic lateral sclerosis.
AB  - We examined regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) in
      4 patients with progressive dementia associated with amyotrophic lateral
      sclerosis (ALS), in 9 patients with classical ALS without dementia, and in 13
      normal controls, using positron emission tomography with oxygen-15 gas and oxygen
      15 labeled carbon dioxide. The mean rCBF and rCMRO2 in the anterior cerebral
      hemispheres decreased significantly in patients with progressive dementia with
      ALS, compared to those in controls. Patients with only ALS showed very mild
      reductions of rCBF and rCMRO2 which were not statistically significant. These
      data suggest that hypoperfusion and oxygen hypometabolism in the anterior
      cerebral hemispheres have an etiological relationship to deterioration of
      intellect in patients with progressive dementia with ALS. A significant reduction
      in the mean rCBF was also found in the cerebellar hemispheres in progressive
      dementia with ALS, while a reduction of mean rCMRO2 was not significant. Remote
      effects analogous to crossed cerebellar diaschisis occurring bilaterally were
      assumed to explain the cerebellar hypoperfusion.

PMID- 8289077
TI  - Low affinity nerve growth factor receptor, adrenal transplant and Parkinson's
      disease.
AB  - Immunohistochemistry of low-affinity nerve growth factor receptor (LNGFR) was
      performed postmortem in the striatum and the adrenal gland of a parkinsonian
      patient with an adrenal to brain transplantation. Few LNGFR-positive fibers were
      observed in the necrotic graft. By contrast numerous immunostained fibers were
      detected in a restricted zone of the host striatum adjacent to the graft,
      corresponding to a selective zone of sprouting of tyrosine hydroxylase-positive
      fibers. This suggests that nerve growth factor or related growth factors may
      promote sprouting of catecholaminergic fibers in the host striatum.

PMID- 8289078
TI  - Anti-GM1/GD1b M-proteins damage human spinal cord neurons co-cultured with
      muscle.
AB  - IgM M-proteins in some motor neuron disease (MND) patients bind immunologically
      to shared determinants on gangliosides GM1 and GD1b. Since patients with these M
      proteins have improved with immunotherapy the antibodies may be important in the
      pathogenesis of MND. To study how the M-proteins might damage motor neurons, we
      established co-cultures of human neurons from spinal cord explants and human
      myotubes. Antibodies from patient but not control serum bound to the cultured
      neurons. Neurons in co-cultures degenerated after incubation with patient but not
      control serum. These results demonstrate that anti-GM1 antibodies can bind to and
      destroy spinal cord neurons that are cultured with muscle. Nerve-muscle co
      cultures can serve as a system to examine effects of anti-GM1/GD1b M-proteins on
      motor neurons.

PMID- 8289079
TI  - On the possibility of autolysosomal processing of skein-like inclusions. Electron
      microscopic observation in a case of amyotrophic lateral sclerosis.
AB  - Hyaline-like inclusions (HLIs) and skein-like inclusions (SLIs) were recently
      observed in the lower motor neurons in amyotrophic lateral sclerosis (ALS). HLIs
      mainly consist of randomly arranged neurofilaments and abnormally large (about 15
      nm) fibrils, while SLIs comprise bundles of the abnormally large fibrils alone.
      Although the abnormal fibrils have been reported to be ubiquitinated in both
      types of inclusions, their final catabolic destination in the neurons is unknown.
      Electron microscopic observation of the lower motor neurons in an ALS case
      revealed several neurons containing SLIs in addition to ones containing HLIs.
      Bundles of SLIs, which were located close to HLIs or were observed by themselves
      without an HLI, were frequently associated with flattened cisterns; some were
      wrapped, some were completely sequestrated, and some were demarcated together
      with a portion of moderately electron dense cytoplasm by cisterns or double
      membraned units. These features resemble reported early stages in the formation
      of autolysosomes, and thus indicate that at least some of the bundles of SLIs or
      parts of them in the lower motor neurons in ALS undergo degradation through the
      autolysosomal pathway.

PMID- 8289080
TI  - An animal model of chronic ischemic neuropathy with proliferative changes of
      nerve microvessel wall.
AB  - In order to produce a model of ischemic neuropathy with neural microvascular
      alterations, sodium laurate was injected into a femoral artery and saline into
      the contralateral artery at the mid-thigh level in Sprague-Dawley rats aged 11
      weeks. In view of the dose-related findings, 0.3 mg sodium laurate dissolved in
      0.1 ml saline was used for the main experiment. The laurate-injected leg showed
      paresis during the experimental period. On day 1-7, various stages of Wallerian
      degeneration and acute microvascular changes were found. At 1 month, regenerating
      myelinated nerve fibers (MNFs) were found at the central or total fascicular area
      mainly in the distal tibial nerve. Morphometric analyses suggested that MNFs
      other than regenerating fibers are atrophic ones. The proliferative changes of
      nutrient microvascular walls were striking. The percent of closed epineurial
      microvessels was significantly larger on the laurate-injected sides and inversely
      associated with the diameter of MNFs. At 7 months, the attenuation of MNFs was
      more prominent and microvascular alterations were persistently observed. These
      pathological findings resemble those of chronic ischemic neuropathy including
      diabetic neuropathy, suggesting that this neuropathy model might provide some
      valuable and useful clues for clarifying the pathogenesis of chronic ischemic
      neuropathy.

PMID- 8289081
TI  - Muscular weakness in the mdx mouse.
AB  - mdx mice are believed to be virtually free from neuromuscular symptoms, despite
      the presence of a degenerative/regenerative process that involves all skeletal
      muscles. We analyzed both the spontaneous motility and treadmill motor activity
      of mdx mice aged 15 days to 6 months. Our results indicate that there is an early
      period, between the end of the second and up to the fifth week of life, when mdx
      mice experience extreme weakness. After this critical period, both spontaneous
      motility and endurance of mdx mice, although lower than those of controls, do not
      show statistically significant differences up to 6 months of age. We also carried
      out a detailed histological analysis of proximal and distal muscle groups in mdx
      mice during this early critical motility period. The occurrence of extensive
      necrosis followed by regeneration and involving proximal muscles before distal
      ones was documented in mice as young as 16-17 days of age and reached a peak at
      day 18. We conclude that dystrophin deficiency induces muscle degeneration and
      significant weakness in mdx mice, but only in an early period. Later on, during
      development, mdx mice adapt to the lack of this protein and do not show
      detectable in vivo functional muscle impairment up to 6 months of age.

PMID- 8289082
TI  - Antibodies to skeletal muscle in myasthenia gravis. Part 2. Prevalence in non
      thymoma patients.
AB  - Anti-skeletal muscle antibodies (AMA) were measured in 340 non-thymoma patients
      with myasthenia gravis (MG) by both an ELISA with citric acid muscle extract and
      by immunofluorescence assay. Three a-AChR negative but AMA-positive patients were
      found. The occurrence of AMA was related to the age at onset in patients with an
      onset of MG beyond 40 years and with duration of disease in patients with an
      earlier onset of MG. This stresses the heterogeneity of late onset and early
      onset MG. Serial measurements in individual patients revealed no evidence for a
      thymic role in the generation of AMA. There was no difference in specificity of
      AMA in early and late onset patients. The presence of AMA in CT-negative patients
      is not necessarily suggestive of a radiological shortcoming in the detection of
      thymoma since in 16 AMA-positive patients from our series no thymoma was found at
      operation or obduction.

PMID- 8289083
TI  - Corticosteroid therapy in Duchenne muscular dystrophy.
AB  - In recent years, various clinical trials have documented the benefit of
      glucocorticoid therapy in the palliation of Duchenne muscular dystrophy (DMD).
      Prednisone therapy, daily or on alternate days, has been confirmed to be of value
      in enhancing muscle strength and function in DMD for up to two years. However,
      there is evidence that corticosteroid treatment results in muscle weakness and
      degeneration. This review, therefore, examines the available studies and
      addresses various possible mechanisms involved in the efficacy of prednisone
      therapy and amelioration of DMD. The progression of DMD is known to be associated
      with profound changes in structure, biochemistry and physiology of the affected
      muscles. It is hypothesized, therefore, that these very changes offer a fortunate
      set of circumstances, and it is owing to these alterations, as well as the well
      known anti-inflammatory/immunosuppressive action of steroid, that muscles in DMD
      are rendered responsive resulting in significant improvement of muscle bulk and
      function.

PMID- 8289084
TI  - Cardiovascular autonomic dysfunction in multiple sclerosis is likely related to
      brainstem lesions.
AB  - Impairment of cardiovascular autonomic reflexes has been described in multiple
      sclerosis (MS), and believed reflecting dysfunction of reflex pathways located
      within the central nervous system. A battery of cardiovascular autonomic tests
      were performed in 40 patients with definite MS: R-R interval variation test, deep
      breathing, Valsalva manoeuvre, blood pressure and heart rate responses to
      standing, sustained handgrip. The results were evaluated by Bayesian analysis, a
      pattern recognition technique. The patients had also magnetic resonance imaging
      (MRI) of brain and in 19 subjects of cervical spinal cord. Deep breathing test
      and sustained handgrip test produced most frequently abnormal results (17.5% and
      40%, respectively). However, only 4 patients (10% had two or more tests abnormal,
      with a very variable pattern. Evaluation by Bayesian analysis revealed 7 patients
      (17.5%) with definite autonomic dysfunction. A correlation was found between the
      confidence level obtained by Bayesian analysis, as index of autonomic function,
      and the Kurtzke brainstem FS score (r = 0.43, P < 0.01). There was a significant
      association between presence of autonomic dysfunction and clinical (P < 0.02) and
      MRI (P < 0.005) evidence of brainstem lesions.

PMID- 8289085
TI  - Neurosteroids in cerebrospinal fluid in neurologic disorders.
AB  - In order to investigate the role of "neurosteroids" in the central nervous system
      (CNS), cerebrospinal fluid (CSF) levels of dehydroepiandrosterone (DHEA) and
      dehydroepiandrosterone sulfate (DHEAS) were determined by radioimmunoassay in 57
      patients with various neurologic disorders and 26 patients with non-neurologic
      disorders. The content of CSF DHEA and DHEAS in patients with Guillain-Barre
      syndrome (GBS), and the content of CSF DHEAS in patients with carcinomatous
      meningitis were significantly higher as compared to non-neurological control
      patients. These changes may be explained by the breakdown of blood-nerve barrier
      in these disorders. A significant positive correlation was observed between DHEAS
      and total protein in CSF. In males but not females, a negative correlation was
      observed between CSF DHEAS and aging. The level of CSF DHEAS, but not DHEA, was
      significantly higher in males than in females.

PMID- 8289086
TI  - Immunofixation superior to plasma agarose electrophoresis in detecting small M
      components in patients with polyneuropathy.
AB  - Monoclonal immunoglobulins (M-components) in blood are found in some patients
      with polyneuropathy and are thought to be of pathogenetic importance, especially
      if the M-component is of IgM isotype. As the finding of an M-component may
      indicate a treatable polyneuropathy, the potential of the method to uncover an M
      component is of importance. Cellulose acetate or agarose electrophoresis used in
      routine practice may miss small M-components covered by other proteins. We
      therefore applied the uncovering and specific method of immunofixation in
      comparison with agarose electrophoresis on patients investigated for
      polyneuropathy. Of 83 consecutive patients, 5 had M-components. Two of these 5
      patients, one with an axonal polyneuropathy and the other with a lower motor
      neuron syndrome, had extra bands on agarose electrophoresis, verified as IgG M
      components by immunofixation. In the 3 additional patients an M-component was
      uncovered only by immunofixation, not seen in the agarose electrophoresis of
      plasma; 2 of them were of IgM isotype and one was of IgG isotype. These 3
      patients were diagnosed as having a demyelinating (i.e., possibly immune
      mediated) polyneuropathy by means of neurophysiology and in one by means of nerve
      biopsy. A 6th patient had 2 small bands in the gamma region on the agarose
      electrophoresis, verified as oligoclonal bands of IgG isotype by immunofixation
      but was not judged as an M-component. Three out of the 83 patients, were judged
      as having motor neuron diseases. All remaining 80 were found to have
      polyneuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289087
TI  - Interleukin-2 secreting cells in multiple sclerosis and controls.
AB  - To evaluate systemic T cell activation and reactivity against putative
      autoantigens in multiple sclerosis (MS), numbers of interleukin-2 (IL-2)
      secreting cells were determined in peripheral blood of 32 patients with MS, 7
      patients with acute aseptic meningitis (AM) and 12 patients with tension headache
      (TH). Numbers of IL-2 secreting cells were higher in MS patients compared to
      patients with AM + TH after stimulation with myelin proteolipid protein (PLP),
      myelin associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein
      (MOG), but not after stimulation with myelin basic protein (MBP). In response to
      MAG, MOG and acetylcholine receptor (AChR) the frequencies of IL-2 secreting
      cells were higher in patients with MS than TH, while there were no differences
      between AM and TH to any of the tested antigens. Between patients with MS and AM
      there was no difference regarding frequency of IL-2 secreting cells in response
      to any of the tested antigens except MAG to which the response was higher in MS
      patients. Six of 10 MS patients had IL-2 secreting cells in response to all four
      myelin antigens (MBP + PLP + MAG + MOG) or to three antigens, while this broad
      reactivity was not found in any control patient. There was no correlation between
      numbers of IL-2 secreting cells in MS patients and clinical variables, including
      exacerbation versus remission, disability and duration of disease. The results
      suggest that the systemic T cell response in patients with MS is directed to
      several antigens.

PMID- 8289088
TI  - Quantitative analysis of copper, zinc and copper/zinc ratio in selected human
      brain tumors.
AB  - Serum copper and zinc concentrations and copper/zinc ratios have been shown to be
      increased in several types of human malignancies, including human brain tumors.
      In this study, copper and zinc levels and copper/zinc ratios were determined by
      atomic absorption analysis in tissue and serum from 29 primary and metastatic
      brain tumor patients. Metastatic carcinomas and malignant gliomas revealed
      significantly higher tissue copper concentrations than control tissues and
      meningiomas. Malignant gliomas demonstrated significantly higher tissue
      copper/zinc ratios. Both serum copper and copper/zinc ratio were significantly
      higher in the metastatic carcinoma group than control; however, serum copper
      levels in malignant glioma patients were not significantly different from control
      tissues. There were no differences both in the serum and the tissue
      concentrations of these trace elements in meningiomas and controls. These data
      suggested that copper, an important angiogenic factors, is accumulated within the
      malignant tissues of metastatic carcinoma and malignant glioma, but not
      meningiomas. These findings may have implications regarding angiogenesis in these
      tumors.

PMID- 8289089
TI  - A sequential cell kinetic study of meningioma cells in primary explant culture
      using bromodeoxyuridine.
AB  - The present study was undertaken to evaluate the sequential BrdU-LI at weekly
      intervals upto four weeks in 18 primary explant cultures of meningiomas. This
      revealed three distinct patterns of growth which could be arbitrarily defined as
      'degenerating' (group I), 'proliferating' (group II) and 'adaptive' (group III)
      types. Interestingly two cases of malignant and two of recurrent meningiomas fell
      into the 'degenerating' group I pattern. The possible explanations for the
      observed relatively higher in vitro LI values compared to lower in vivo values as
      reported in the literature and the theoretical implications of the three distinct
      patterns of sequential LI values are discussed.

PMID- 8289090
TI  - Vertebral collapse with quadraparesis due to metastatic gliobla multiforme: case
      report and review of the literature.
AB  - A case is reported of a patient rendered quadraparetic following collapse of a
      cervical vertebra due to neoplastic invasion by metastatic glioblastoma
      multiforme. The case is discussed in light of a review of the world literature
      regarding the clinical incidence and significance of metastasis of glial tumors.
      It is recommended that all patients with high grade glial tumors who complain of
      back pain be evaluated with plain radiographs and MRI of the spine or 99Tc bone
      scan. The management of pathologic spine fractures from metastatic glial tumors
      with accompanying spinal instability or spinal cord compression due to
      intracanalicular bone should aim for immediate surgical decompression and
      stabilization followed by involved field irradiation.

PMID- 8289091
TI  - Staurosporine differentially inhibits glioma versus non-glioma cell lines.
AB  - We have previously demonstrated that the protein kinase C (PKC) activity of human
      glioma cell lines was significantly elevated (by 3 orders of magnitude) when
      compared to non-malignant adult human glia, and that the proliferation rate of
      several established human glioma cell lines correlated with the measured protein
      kinase C activity. The purpose of this study was to determine whether 1) elevated
      PKC activity was also a characteristic of fast growing cell lines of non-glial
      origin, 2) the proliferation rate of non-glioma cell lines correlated with their
      PKC activity and 3) the proliferation of non-glioma cell lines could be inhibited
      by staurosporine, a relatively selective PKC inhibitor, which significantly
      attenuates the growth of glioma cells. Eight established human non-glioma cell
      lines (bladder, colorectal, rhabdomyosarcoma-oligodendrocyte hybrid, melanoma,
      cervix, and fibroblast) were compared to the highly proliferative A172 glioma
      cell line. PKC activity was significantly higher in the glioma cell lines even
      though 3 of 8 of the non-glioma lines had higher proliferation rates than A172.
      In non-glioma cell lines, no correlation was found between the PKC activity and
      proliferation rates. Staurosporine was more effective in decreasing the
      proliferation of three glioma cell lines compared to the non-glioma cell lines.
      We conclude that PKC activity is differentially increased in glioma cell lines
      and that their proliferation rate is more sensitive to inhibition by
      staurosporine. Targetting the PKC system may prove to be of therapeutic benefit
      to patients with malignant gliomas.

PMID- 8289092
TI  - A transmission and scanning electron microscopic study of tumoral and peritumoral
      microblood vessels in human gliomas.
AB  - The tumor microblood vessels (MBVs) of 25 cases of gliomas of varying grades were
      studied and compared with those in peritumoral region using both transmission and
      scanning electron microscopy (TEM and SEM). The TEM study revealed numerous
      villous projections with pinocytotic vesicles (PCVs) and large vacuoles (LVs)
      concentrated mainly at the luminal aspect in tumor MBVs which increased with
      increasing severity of edema. The peritumoral MBVs, in addition to showing some
      increase in villous projections on the luminal surface, also showed increased
      number of PCVs and LVs concentrated at the abluminal aspect with some of them
      even communicating with the extravascular space. The SEM study largely
      corroborated the TEM findings. The sites of formation of PCVs and LVs appeared as
      small pits or large craters on the luminal surface of the endothelial cells of
      tumor MBVs. We feel that the morphological evidence of increased permeability in
      tumor MBVs represents their role in the development of edema and that the
      occurrence of reverse pinocytosis in peritumoral MBVs is a distinct possibility
      which may be associated with resorption of edema fluid.

PMID- 8289093
TI  - Loss in expression of the retinoblastoma gene product in human gliomas is
      associated with advanced disease.
AB  - The retinoblastoma susceptibility gene (RB), the prototype of the class of tumor
      suppressor genes, is inactivated in a number of human malignancies. We
      investigated a possible role of RB in human brain tumors. Immunoprecipitation
      revealed frequent loss of RB protein expression in glioma cell lines (8/24),
      which was accompanied by lack of RB encoded transcripts. Among seventeen primary
      brain tumors studied by Western blotting, loss of Rb protein expression was
      observed in WHO grade 3 and 4 gliomas (3/10). However, none of the low grade
      gliomas and the other primary brain tumors investigated lacked RB protein
      expression. These data suggest a role for RB in glial malignancy, and loss of Rb
      expression appears to be associated with glial tumor progression.

PMID- 8289094
TI  - Postoperative hypofractionated radiotherapy versus conventionally fractionated
      radiotherapy in malignant gliomas. A preliminary report on a randomized trial.
AB  - A prospective randomized study of 108 patients with cerebral malignant gliomas
      was carried out at the Department of Radiation Oncology of Maria Sklodowska-Curie
      Memorial Center in Krakow. 44 patients with histologically proven glioblastoma
      multiforme and 64 patients with anaplastic astrocytoma received postoperative
      radiotherapy. Patients were randomized to two treatment arms: Conventionally
      Fractionated Radiotherapy (CFR) and Hypofractionated Radiotherapy (HF). In the
      CFR group, the whole brain was irradiated to the total dose of 50 Gy in 25
      fractions over 5 weeks, then a 10 Gy 'boost' in 5 fractions in 5 days was
      delivered to the site of the primary lesion. In the HF group, there were 3
      courses of irradiation separated by a one month interval. In each of the two
      first series the patients received 20 Gy in 5 fractions in 5 days to the whole
      brain, and in the third course, 10 Gy 'boost' in 5 days was delivered as in the
      CFR regimen. The tolerance to treatment has been found to be good in both groups.
      The 2-year actuarial survival rate for patients with anaplastic astrocytoma was
      22% for CFR and 18% for HF. Patients with glioblastoma multiforme treated with HF
      had a better prognosis in comparison to the CFR group with the two-year actuarial
      survival rates being 23% and 10%, respectively. This difference is statistically
      significant at the 0.05 level.

PMID- 8289095
TI  - Multiple intracranial melanoma metastases treated with surgery and radiosurgery
      with long term control. A case report.
AB  - A case of malignant melanoma with multiplex brain metastases is described, where
      both surgical and radiosurgical treatment was applied. Due to CNS manifestations
      the patient was operated on in two sessions. First the symptomatic large tumor
      was removed, and the other, small lesion which could not be reached from the same
      approach was operated later. The primary skin lesion was discovered and removed
      between the two operations. A CT scan three months after the second operation
      revealed recurrence at the site of the first operation, and the appearance of two
      new tumors. The intracranial neoplasms were treated in one session by
      stereotactic radiosurgery using a linear accelerator. Six months after this
      treatment a new skin lesion was removed and the patient received DTIC therapy.
      Successive CT scans after the irradiation showed a steady regression of the
      radiosurgically treated tumors, and more than one year after the irradiation no
      tumor could be detected on the CT scans.

PMID- 8289096
TI  - Prevention of readmission in elderly patients with congestive heart failure:
      results of a prospective, randomized pilot study.
AB  - OBJECTIVE: To determine the feasibility and potential impact of a non
      pharmacologic multidisciplinary intervention for reducing hospital readmissions
      in elderly patients with congestive heart failure. DESIGN: Prospective,
      randomized clinical trial, with 2:1 assignment to the study intervention or usual
      care. SETTING: 550-bed secondary and tertiary care university teaching hospital.
      PATIENTS AND PARTICIPANTS: 98 patients > or = 70 years of age (mean 79 +/- 6
      years) admitted with documented congestive heart failure. INTERVENTIONS:
      Comprehensive multidisciplinary treatment strategy consisting of intensive
      teaching by a geriatric cardiac nurse, a detailed review of medications by a
      geriatric cardiologist with specific recommendations designed to improve
      medication compliance and reduce side effects, early consultation with social
      services to facilitate discharge planning, dietary teaching by a hospital
      dietician, and close follow-up after discharge by home care and the study team.
      MEASUREMENTS AND MAIN RESULTS: All patients were followed for 90 days after
      initial hospital discharge. The primary study endpoints were rehospitalization
      within the 90-day interval and the cumulative number of days hospitalized during
      follow-up. The 90-day readmission rate was 33.3% (21.7%-44.9%) for the patients
      receiving the study intervention (n = 63) compared with 45.7% (29.2%-62.2%) for
      the control patients (n = 35). The mean number of days hospitalized was 4.3 +/-
      1.1 (2.1-6.5) for the treated patients vs 5.7 +/- 2.0 (1.8-9.6) for the usual
      care patients. In a prospectively defined subgroup of patients at intermediate
      risk for readmission (n = 61), readmissions were reduced by 42.2% (from 47.6% to
      27.5%; p = 0.10), and the average number of hospital days during follow-up
      decreased from 6.7 +/- 3.2 days to 3.2 +/- 1.2 days (p = NS). CONCLUSIONS: These
      pilot data suggest that a comprehensive, multidisciplinary approach to reducing
      repetitive hospitalizations in elderly patients with congestive heart failure may
      lead to a reduction in readmissions and hospital days, particularly in patients
      at moderate risk for early rehospitalization. Further evaluation of this
      treatment strategy, including an assessment of the cost-effectiveness, is
      warranted.

PMID- 8289097
TI  - Cholesterol-lowering therapy: what patients expect in return.
AB  - OBJECTIVE: To assess variability in patients' values and preferences regarding
      cholesterol-lowering therapy. DESIGN: A descriptive study. Patients currently
      receiving cholesterol-lowering therapy were interviewed using the time tradeoff
      and standard reference gamble techniques of utility assessment. SETTING: Internal
      medicine clinics of a military medical center. PARTICIPANTS: Thirty-five
      patients, clinically free of coronary disease, receiving cholesterol-lowering
      therapy for at least three months. RESULTS: When the time tradeoff method was
      applied, 12 (34%) of the patients indicated that less than one month of
      additional life would be a fair return for adhering to their current therapy for
      the rest of their lives, while 13 (37%) patients required more than one
      additional year of life, and four (11%) required at least five years. By the
      standard reference gamble method, 18 (51%) patients would not have accepted a
      risk of one in a thousand of imminent death (in 30 days) in hopes of obtaining a
      normal life expectancy off therapy, while 14 (40%) would have agreed to a 1% or
      greater risk in order to avoid therapy. CONCLUSIONS: While many patients
      apparently expected very little in return for adhering to therapy, many others
      may not be getting "what they bargained for."

PMID- 8289098
TI  - Home blood glucose monitoring: effectiveness in a general population of patients
      who have non-insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To determine whether home blood glucose monitoring as used by non
      insulin-dependent diabetes mellitus patients followed in primary care nonresearch
      clinics improves glycemic control or reduces utilization of the outpatient
      laboratory. DESIGN: A retrospective chart review for 229 patients receiving
      outpatient supplies for home testing of either blood or urine. SETTING: A variety
      of nonresearch clinics at a Veterans Affairs Medical Center, a teaching hospital
      affiliated with an academic university medical center. PATIENTS: Outpatient
      veterans followed in diabetes, primary care, internal medicine, or endocrine
      clinics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean
      glycosylated hemoglobin for an unselected group monitoring glycemic control by
      urine testing only was 11.32% and for those using blood monitoring was 11.37%.
      Frequency and duration of monitoring had no apparent impact on glucose control.
      There was no decrease in the utilization of the laboratory among those patients
      practicing home blood glucose monitoring. CONCLUSIONS: For non-insulin-dependent
      diabetic patients followed in a nonresearch clinic setting, the benefits of home
      blood glucose monitoring remain to be proven.

PMID- 8289099
TI  - Predictors of failure to attend scheduled mammography appointments at a public
      teaching hospital.
AB  - OBJECTIVE: To identify patient, institutional, and physician characteristics that
      predict failure to attend scheduled mammography appointments. DESIGN:
      Retrospective chart review. SETTING: Medicine clinic at an urban public teaching
      hospital. PATIENTS: All 907 women aged 40 years and more scheduled for
      mammography from March 1990 to June 1991. MEASUREMENTS AND MAIN RESULTS: The main
      outcome measure was whether a woman kept her scheduled mammography appointment.
      Potential predictor variables included patient age, race, marital status, and
      insurance status; waiting interval to obtain a mammography appointment; and
      physician gender, level of training, country of training, and native language.
      The rate of failed mammography appointments was 23%. Univariate analysis showed
      that appointment failure was associated with age (p = 0.03), with the lowest
      failure rates (19%) among women aged 60 years and more. Appointment keeping
      varied significantly by race (p = 0.01), largely because of the higher failure
      rate among Native American women (36%). Insured women had a failure rate of 22%
      vs 33% for uninsured women (p = 0.01). The rate of failed appointments varied
      significantly by waiting interval (p = 0.05), with a peak failure rate of 27% for
      appointments scheduled 14-27 days in advance. None of the physician variables was
      associated with appointment failure. Multivariate analysis confirmed these
      results. CONCLUSIONS: Interventions to improve completion of breast cancer
      screening should include additional efforts targeted at groups with high rates of
      appointment failure, such as women under the age of 60, the uninsured, and Native
      Americans. Long waiting intervals to obtain mammography appointments may decrease
      compliance.

PMID- 8289100
TI  - Predictors of physicians' responses to woman abuse: the role of gender,
      background, and brief training.
AB  - OBJECTIVE: To assess the relationship between gender, background, and brief
      training and physicians' detection of and treatment for woman abuse. DESIGN:
      Quasi-experimental and correlational designs, plus control for background
      factors. SETTING: Two residency training programs: general internal medicine and
      family practice. PARTICIPANTS: Thirty-five participants were residents and four
      were faculty members; 17 were trained and 22 were untrained physicians; 20 were
      women and 19 were men. MEASURES: Immediately after an encounter with each
      physician, a standardized patient rated speed of detection, history taking,
      planning, and focus on psychosocial issues. RESULTS: Women tended to detect the
      abuse earlier and take a more thorough history. Trained and untrained groups did
      not differ on any outcome variable. Prior professional training and having
      personally known a victim were positively associated with outcome, especially
      among men. CONCLUSIONS: Referrals might best be made to women
      counselor/advocates. More extensive training of all personnel may be needed than
      that provided in this study.

PMID- 8289101
TI  - Quantitating qualitative issues in residency training: development and testing of
      a scaled program evaluation questionnaire.
AB  - OBJECTIVES: To develop and test a scaled program evaluation questionnaire
      focusing on resident satisfaction with workload, learning environment, and
      stress. DESIGN/PARTICIPANTS: Phase 1: A cross-section of 92 residents from five
      programs completed questionnaires for factor analysis and descriptive statistics.
      Phase 2: A three-year prospective study of questionnaire responses in a single
      program. QUESTIONNAIRE DEVELOPMENT: After extensive literature review, 33 Likert
      scaled statements were written, dealing with situational, personal, and
      professional issues. After pilot testing, the 92 questionnaires obtained in Phase
      1 were factor analyzed, resulting in three distinct scales: workload,
      faculty/learning environment, and stress. INTERVENTIONS: Program changes in Phase
      2 included the introduction of a night float between 1989 and 1990, and an
      increase in senior resident call between 1990 and 1991. RESULTS: Phase 1: The
      first-year residents reported significantly less stress and generally greater
      satisfaction with workload and learning environment than did the second- or third
      year residents. Marked differences between programs were also present in the mean
      scores on all three scales. Phase 2: The introduction of a night float did not
      significantly affect response to the questionnaire, but the increase in nights on
      call significantly increased stress and dissatisfaction with the faculty/learning
      environment. CONCLUSIONS: This study demonstrates the techniques needed to
      develop and use scaled program evaluation questionnaires. It is hoped that
      widespread use and validation of such instruments may result in greater
      responsiveness to the needs of trainees and more facilitative environments in
      which to acquire medical knowledge.

PMID- 8289102
TI  - An analysis of the cost and revenue of an expanded medical residency.
AB  - OBJECTIVE: To analyze the additive costs and revenues resulting from expansion of
      a medical residency and associated subspecialty programs. METHODS: Direct and
      indirect costs of the residency program were analyzed as was reimbursement for
      the costs of the residency. To determine whether expansion of the residency
      affected cost of care, the authors compared the costs of care on the teaching
      service and nonteaching services. RESULTS: The number of residents increased from
      18 medical resident and subspecialty fellows in the 1988 academic year to 36
      medical residents and 12 subspecialty fellows in the 1991 academic year. Total
      measured costs increased by $2,036,570 to $3,911,196. Reimbursement increased to
      $5,319,117, of which $2,290,221 was attributed to the increase in the number of
      residents. Net income from the residency after subtracting costs increased by
      $815,714 to a total of $1,407,971, excluding any higher costs at the authors'
      hospital that were an indirect result of the teaching program. Costs for the same
      diagnosis-related groups (DRGs) were not significantly different on the teaching
      and nonteaching services. CONCLUSIONS: Expanding the medical residency increased
      the net income available to offset the higher costs per DRG at the hospital.
      These costs did not increase in proportion to the increase in resident numbers.
      Increased revenue came primarily from Medicare indirect cost reimbursement. A
      reduction in this rate from 7.7% to less than 4.1% would have resulted in a net
      loss for medical education costs. Present reimbursement policy is not aligned
      with actual costs or public policy goals. This may have undesired effects both
      now and in the future.

PMID- 8289103
TI  - Patient preferences for novel therapy: an N-of-1 trial of garlic in the treatment
      for hypertension.
AB  - The authors used the N-of-1 clinical trial methodology to obtain insights about a
      patient's preference for garlic for the management of his hypertension. The 61
      year-old man received garlic, 500 mg by mouth three times a day (3 weeks), or
      identical placebo (3 weeks) in three treatment pairs. While the patient was
      taking garlic the mean systolic blood pressure decreased by 2 mm Hg (95%
      confidence interval 0.4 to 4.7, p < 0.05), and the diastolic blood pressure
      decreased by 2.4 mm Hg (95% confidence interval 0.4 to 4, p < 0.025). The
      treatment effect of garlic was small, but the patient believed continuing garlic
      for the management of his hypertension was justified.

PMID- 8289104
TI  - Sir William Osler: a brief review.

PMID- 8289106
TI  - Evaluation of liver size by physical examination.

PMID- 8289107
TI  - Local logic and national nonsense: financing of graduate medical education
      encourages expansion of residencies.

PMID- 8289105
TI  - Infections due to antibiotic-resistant gram-positive cocci.
AB  - Gram-positive cocci are becoming increasingly resistant to traditionally used
      antimicrobial agents. Staphylococcus aureus, coagulase-negative staphylococci,
      the enterococcus, and Streptococcus pneumoniae are the most commonly encountered
      of such pathogens in clinical practice. Clinicians should be keenly aware of the
      usual types of infections that are caused by these organisms and the importance
      of documenting susceptibilities of infecting strains. The basic mechanisms of
      resistance should be familiar to clinicians so that an inappropriate empiric
      regimen will not be selected (e.g., addition of a beta-lactamase inhibitor for
      penicillin-resistant pneumococci). Vancomycin remains the agent of choice,
      sometimes in combination with gentamicin and/or rifampin, for most cases of
      infection due to these resistant gram-positive organisms. Last, increased efforts
      toward prevention, such as strict adherence to infection control measures,
      selective use of broad-spectrum antibiotics, and increased use of pneumococcal
      vaccine, may be useful to help stem the rising tide of infections due to
      resistant gram-positive cocci.

PMID- 8289108
TI  - DVT prophylaxis in total hip replacement.

PMID- 8289109
TI  - Spectra of the formaldehyde-induced ultraweak luminescence from yeast cells.
AB  - An increase in the intensity and distinct spectral changes of ultraweak
      luminescence from the yeast Saccharomyces cerevisiae were measured when the
      metabolism of cells was drastically altered. A small emission peak and a red
      emission band 680-850 nm appeared when air-dried cells were imbibed in water.
      Lethal concentrations of HCHO (0.01%-10%) elicited a 2500 fold increase of the
      emission intensity and distinct spectral alterations. A transient 500-580 nm
      emission appeared in the initial phase of interaction. Then a gradually
      increasing long-lasting red emission band centered around 620 nm predominated in
      the total spectral range covering 470-850 nm. These emissions were not correlated
      with minor changes in fluorescence emission and excitation spectra originating
      from tryptophan, flavins, and unidentified emitters.

PMID- 8289110
TI  - Photohemolytic activity of lichen metabolites.
AB  - Irradiation of pannarin 1'-chloropannarin and antranorin with 366 nm light leads
      to significant hemolysis in a red cell suspension. However, their mechanism of
      action is different. Hemolysis induced by pannarin and 1'chloropannarin increases
      in the presence of oxygen, whereas hemolysis induced by atranorin is higher in
      nitrogen-purged solutions. The effect of free radical scavengers, and the lack of
      effect of D2O in the medium, suggest that the hemolysis induced by pannarin and
      1'chloropannarin is not mediated by (1)O2. Both the hemolytic and photohemolytic
      activities of the depsidones, particularly 1'-chloropannarin, increase when the
      temperature increases from 21 to 37 degrees C.

PMID- 8289111
TI  - Photosensory transduction in ciliates. Role of intracellular pH and comparison
      between Stentor coeruleus and Blepharisma japonicum.
AB  - To test the hypothesis that light signal transduction in the unicellular ciliates
      Stentor coeruleus and Blepharisma japonicum involves a change in intracellular pH
      as an initial signal following photoexcitation, we studied the dependence of the
      photophobic responses of the cells to changes in extracellular pH and to reagents
      that specifically affect intracellular pH. The extracellular pH can modify not
      only the intracellular pH, but can even reverse the sign of the pH gradient
      across the cell membrane. Thus, as predicted by the hypothesis, low extracellular
      pH reversibly inhibited the photophobic response of the ciliates. The
      intracellular pH-modulating reagents tested included ammonium chloride, a
      membrane-permeable weak acid that lowers the intracellular pH, and the
      protonophores carbonylcyanide m-chlorophenyl-hydrazone (CCCP) and carbonylcyanide
      p-(trifluoromethoxy)-phenyl-hydrazone (FCCP), which collapse the pH gradient
      across the cell membrane. The low pH and protonophore treatments caused a gradual
      inhibition of the photophobic responses in both ciliates. The observed reduction
      of the responsiveness of the cells to visible light can be attributed to the
      alteration of the intracellular pH, which is suggested to play a specific role in
      the photosensory transduction in both Stentor coeruleus and Blepharisma
      japonicum.

PMID- 8289112
TI  - Fluence-rate-dependent photosensitized oxidation of NADH.
AB  - The photosensitizing activity of dimethoxyhaematoporphyrin, excited by a laser
      pulse at 532 nm (YAG-Nd3+), was investigated using reduced nicotinamide adenine
      dinucleotide (NADH) as a substrate. The photo-oxidative modification of NADH was
      monitored by measuring the absorbance at 340 nm. The use of nanosecond pulses (15
      and 0.5 ns) resulted in photosensitized NADH oxidation which depended on the
      fluence but not on the fluence rate up to a peak fluence rate of 10(7) W cm-2. At
      higher fluence rates a decrease in NADH photo-oxidation was observed, as well as
      on irradiation with picosecond pulses (35 ps). Stern-Volmer assay of the
      quenching by sodium azide revealed a decrease in quenching efficiency with
      increasing peak fluence rate. Oxidation of NADH was not suppressed by the
      addition of 20 mM sodium azide at peak fluence rates above 6 x 10(9) W cm-2. This
      observation, as well as the significant bleaching of dye absorption, indicates
      excitation of the photosensitizer into higher lying excited singlet states and
      the involvement of processes other than photodynamic action.

PMID- 8289113
TI  - In vitro phototoxicity of clofibrate. Photochemical and photohemolytic studies on
      its metabolite clofibric acid.
AB  - Aqueous or methanolic solutions of clofibrate and clofibric acid are photolabile
      towards UVB light under aerobic as well as anaerobic conditions. Nine
      photoproducts have been identified; their formation involves primary cleavage of
      the carbon-halogen bond or of the aryloxy-carbon bond, followed by hydrogen
      abstraction and/or radical recombination. Clofibric acid is phototoxic in vitro
      as indicated by the photohemolysis test, under both oxygen and argon atmospheres,
      although the photohemolysis rate is markedly higher under aerobic conditions.
      Partial inhibition of this process on addition of butylated hydroxyanisole (BHA),
      reduced glutathione (GSH), sodium azide (NaN3) or 1,4-diazabicyclo[2.2.2]octane
      (DABCO) suggests the involvement of type I as well as type II mechanisms.

PMID- 8289114
TI  - Porphyrin-melanin interaction: effect on fluorescence and non-radiative
      relaxations.
AB  - Optical techniques and pulsed-laser, time-resolved photoacoustics (PA) were
      employed to obtain information on the mechanism of interaction between cationic
      zinc tetrabenzilpyridilporphyrin (ZnTBzPyP) and synthetic L-Dopa melanins.
      Synthetic eumelanin and pheomelanin strongly quench the fluorescence of ZnTBzPyP,
      but Stern-Volmer plots suggest a mechanism of interaction quite different for the
      two pigments. This diversity was confirmed by PA: for eumelanin no thermal
      relaxation was observed other than prompt heat, whereas for the complexed form of
      ZnTBzPyP with pheomelanin we were able to detect a heat-emitting species with a
      non-radiative lifetime in the microsecond range. The involvement of oxygen in the
      photophysics of the complexes formed between the cationic porphyrin and the two
      pigments was demonstrated, but its role has yet to be described.

PMID- 8289115
TI  - Effect of extracellularly generated singlet oxygen on gram-positive and gram
      negative bacteria.
AB  - In the separated surface-sensitizer system, a photosensitizer is physically
      separated from the substrate by a thin air layer under such conditions that only
      singlet oxygen can reach and oxidize the substrate, preventing the competition by
      type I photosensitized processes. This method has been used to study the reaction
      of singlet oxygen with Gram-positive (Streptococcus faecium) and Gram-negative
      (Escherichia coli) bacterial strains. Studies on cell samples exposed to singlet
      oxygen for different periods of time show a drastic decrease in survival for S.
      faecium, while E. coli becomes sensitive only when the integrity of the outer
      membrane is altered by treatment with CaCl2 or tris(hydroxymethyl)aminomethane
      ethylenediaminetetraacetic acid (Tris-EDTA). Biochemical and ultrastructural
      analyses suggest that the cytoplasmic membrane and the genetic material are the
      main sites damaged by singlet oxygen.

PMID- 8289116
TI  - Submicron emulsions as colloidal drug carriers for intravenous administration:
      comprehensive physicochemical characterization.
AB  - Submicron injectable emulsions have been gaining more and more attention in the
      last few years, mainly as a vehicle for the intravenous administration of
      lipophilic drugs rather than as an improved delivery system for drug targeting.
      Submicron emulsions are available, clinically well accepted, and successfully
      marketed. Novel original emulsion formulations are being extensively investigated
      and already exhibit improved pharmacological activity; this fact underlines the
      promising therapeutic properties of these colloidal drug carriers as vehicles for
      potent lipophilic drugs. It is therefore essential to carry out a comprehensive
      physicochemical characterization of these submicron emulsions. It is the
      objective of the present review to emphasize the need for physicochemical studies
      in the design of new submicron emulsion drug delivery systems and to describe the
      different approaches available for carrying out such a complete examination of
      the emulsion colloidal drug carrier system.

PMID- 8289117
TI  - Model describing transdermal iontophoretic delivery of lidocaine incorporating
      consideration of cutaneous microvascular state.
AB  - A three-compartment pharmacokinetic model describing percutaneous absorption of
      iontophoretically driven topically applied lidocaine in the isolated perfused
      porcine skin flap is presented. Delivery from the active (drug-dosed) electrode
      to skin is estimated as a ramp input profile. Model parameters were estimated
      separately for dosing (4 h current-on) and washout (4 h current-off) periods in
      experiments with coadministered vasoactive drugs [tolazoline (vasodilator) and
      norepinephrine (vasoconstrictor)] and controls (lidocaine alone). The model
      presented was able to predict 8-h lidocaine absorptions and compartmental mass
      profiles for each of the three treatments, was able to document vascular effects
      of co-iontophoresed vasoactive compounds, and gives insight into the factors that
      modulate cutaneous disposition of iontophoretically delivered lidocaine in a
      biologically relevant model approximating in vivo delivery.

PMID- 8289118
TI  - A multidimensional deconvolution method for evaluating the absorption of drugs
      undergoing reversible metabolism and presystemic metabolite formation.
AB  - A general multidimensional deconvolution method is developed primarily for
      application to the bioavailability assessment of drugs with reversible
      metabolism. The proposed approach involves fitting continuous functions to the
      experimental data and then applying a numerical deconvolution algorithm to the
      fitted curves. It is shown how the method may be used to determine the rates and
      extends of drug absorption and presystemic formation of interconversion
      metabolites. The proposed method is implemented as a FORTRAN subroutine called
      DCVSYS for the general multidimensional deconvolution problem involving any
      continuous functions and as a user-friendly PC-compatible program called NDCREV
      for evaluating the absorption of drugs undergoing reversible metabolism. The
      methods and computer programs are demonstrated by application to simulated drug
      and metabolite concentrations for a drug with reversible metabolism.

PMID- 8289119
TI  - Cyproheptadine analogues: synthesis, antiserotoninergic activity, and structure
      activity relationships.
AB  - A series of cyproheptadine related compounds was synthesized and tested
      pharmacologically. In comparison with cyproheptadine, these compounds do not have
      a central ring and some contain groups other than N-methyl. Synthesis was carried
      out with low-valent titanium to generate the exocyclic double bond. The
      serotoninergic activity of the compounds was determined by standard determination
      of pA2 (-log of the motor concentration of antagonist required to maintain a
      constant response when concentration of agonist is doubled) for the inhibition of
      serotonin-induced contractions in rat stomach fundus. Two of the nitrogen
      containing compounds were active, but their activities were lower than that of
      cyproheptadine. Structure-activity relationships were studied by Mulliken net
      charges, molecular electrostatic potentials, and conformational analysis;
      activities are better correlated with electrostatic potentials than with net
      charges. The decrease in potency of the open cyproheptadine analogues may be due
      to "dilution" of the active conformer as the result of their conformational
      flexibility.

PMID- 8289120
TI  - Diffusion and concentration profiles of drugs in gels.
AB  - A versatile membraneless method was used to study the diffusion of acetaminophen,
      ibuprofen, indomethacin, theophylline, and chlorpheniramine in thermoreversible
      gels. Two independent ways to calculate the diffusion coefficients and to verify
      Fickian transport are presented; the most sensitive criterion for Fickian
      transport being an agreement between the concentration profile for the drug in
      the gel and the free diffusion model. The diffusion of acetaminophen, ibuprofen,
      and indomethacin was studied at different temperatures in 1% (w/w) agarose gels.
      The diffusion coefficients for these drugs were found to be essentially the same
      as in water, and the apparent diffusion activation energies are close to that for
      self diffusion of water (4.62 kcal/mol), indicating a common mechanism for the
      diffusion of these drugs in the gel. The diffusivity of chlorpheniramine was also
      studied in 4% (w/w) agarose gels or with part of the agarose substituted with
      other polymers (e.g., chitosan and sodium alginate). These two oppositely charged
      polymers, mixed together, were found to occupy an "equivalent polymer volume"
      that was three times larger than the same amount of each of the constituents.
      When chitosan and gelatin-B were mixed into the agarose gel, non-Fickian
      transport resulted. Such non-Fickian transport was also observed with
      theophylline diffusing in a mixture of agarose, chitosan, and sodium alginate at
      a low pH.

PMID- 8289121
TI  - Surface recovery and stripping methods to quantify percutaneous absorption of
      caffeine in humans.
AB  - The percutaneous absorption of caffeine from two vehicles, an emulsion and an
      acetone solution, was quantified by in vivo techniques in humans. A surface
      recovery technique over a 6-h application and a stripping method after a 30-min
      application were performed on the volar aspect of the forearm on 12 volunteers.
      Caffeine was assessed by HPLC. Two phases were distinguished in the percutaneous
      absorption of caffeine: a higher filling up of the stratum corneum with the oil
      in-water emulsion than with the acetone solution, which was then followed by a
      steady-state flux corresponding to the penetration in the living tissues. The
      permeability constants (Kp) with emulsion and acetone were 1.59 x 10(-4) and 9.53
      x 10(-8) cm/h, respectively. The stripping method showed concentrations of
      caffeine in stratum corneum that were five times higher with emulsion (212
      ng/cm2) than with acetone (37 ng/cm2). With acetone as a vehicle, approximately
      40% of caffeine of the cornfield layer was found around the treated area. This
      sizeable lateral spread within the stratum corneum was not observed with the
      emulsion.

PMID- 8289122
TI  - Bioavailability of racemic ibuprofen and its lysinate from suppositories in
      rabbits.
AB  - Plasma concentration (C)-time (t) plots of ibuprofen from suppositories in
      rabbits are characterized by the sum of two exponentials, C = Be-lambda 2t-Ae
      lambda 1t. When A exceeds B, there is a lag time (tlag = tc = 0) before the start
      of absorption. Evidence for dose-dependent area under the curve (AUC) of C versus
      t values is presented with the implication that elimination rate constants (ke)
      decrease and the AUC/dose ratio increase with dose. The lack of significant
      differences between the AUC values from suppository and the intravenous studies
      with similar doses implies complete absorption of ibuprofen from all the
      suppositories studied. The absorption rate constants (ka) were estimated on the
      presumption of complete absorption and dose-dependent elimination. Ibuprofen
      lysinate was absorbed significantly more readily than the free acid from
      suppositories. The lysinate suppository with a lipophilic surfactant had a higher
      absorption rate constant than that with a hydrophilic surfactant. The ka values
      did not significantly differ for a twofold difference in dose. Equations were
      developed to calculate true AUC and area under the moment curve (AUMC) values
      when A exceeds B, and to transform C versus t plots to the origin with A' = A =
      B. Times of maximum peak heights, mean residence (MRT), and mean absorption times
      (MAT = 1/ka) of suppositories when A > B are shown to differ by the lag time (tc
      = 0) from the plots of C versus t transposed to the origin. Although corrected
      AUC values when A > B are equal to the AUC values of C versus t plots transposed
      to the origin (A' = A = B), the corrected AUMC values when A > B significantly
      differ from the AUMC values for the C versus t plots transposed to the origin.

PMID- 8289123
TI  - Increased erythrocyte and protein binding of codeine in patients with sickle cell
      disease.
AB  - Erythrocyte binding and plasma protein binding of codeine in sickle cell patients
      and healthy controls were determined. A reversed-phase HPLC procedure was used
      for codeine analysis. Codeine was extracted from alkalinized plasma, separated on
      a CN column, and assayed by fluorescence detection. The erythrocyte-buffer
      partition coefficient was significantly higher in sickle cell patients (1.72 +/-
      0.21) than in healthy controls (1.25 +/- 0.14). No time dependence of
      partitioning was observed. The fraction of codeine bound to plasma proteins,
      determined by ultrafiltration, was significantly higher in sickle cell patients
      (66.0% +/- 8.6%) than in healthy controls (30.5% +/- 2.7%). No concentration
      dependence of erythrocyte or protein binding was observed. Further studies were
      performed to elucidate the binding mechanisms. From a ghost cell binding study it
      was concluded that the major binding sites for codeine are in the cell membrane.
      A decrease in codeine binding was observed in the presence of bilirubin. Codeine
      binding to alpha 1-acid glycoprotein was found to be minimal. The levels of alpha
      1-acid glycoprotein and other glycoproteins in sickle cell patients and healthy
      controls were measured by glycoprotein electrophoresis. The results showed no
      significant difference between the two groups. Plasma protein electrophoresis was
      performed for the two groups. The results showed a significant difference in
      gamma-globulin levels between sickle cell patients and healthy controls. Codeine
      is known to bind to gamma-globulin, a fact that may explain in part the observed
      increase in the plasma protein binding of codeine in sickle cell
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289124
TI  - Noninvasive assessment of anesthetic activity of topical lidocaine formulations.
AB  - The effectiveness of a series of lidocaine formulations in producing anesthesia
      after topical application was evaluated in human volunteers. The formulations,
      five suspensions in 20% propylene glycol and one cream, were applied to the
      forearms for 3 h with occlusion with Hilltop chambers. Testing for anesthesia was
      performed electrometrically. All lidocaine-containing formulations produced
      significantly greater anesthesia than the blanks. The formulation containing
      tetradecyltrimethylammonium bromide produced greater anesthesia than that
      containing octadecyltrimethylammonium chloride. Changing the pH of the
      formulation from 7.9 to 10.0 had no significant effect. Other formulations
      (sodium lauryl sulfate and the cream) were no more effective than the plain
      formulation without surfactants. The rank order for the suspension formulations
      was the same as for steady-state permeation in in vitro experiments. However,
      application of the cream formulation produced greater effect in vivo than was
      anticipated from in vitro flux values.

PMID- 8289125
TI  - Evaluation of local anesthesia provided by transdermal patches containing
      different formulations of tetracaine.
AB  - Topical formulations of tetracaine in vehicles of propylene glycol and saline are
      tested on human volunteers with standard occlusive, adhesive, transdermal
      patches. The effects of formulation composition, dose, and onset time are
      investigated. Dose-response studies indicate that the optimum formulation for the
      diffusion of tetracaine in vivo is 60% free base and 40% acid salt (w/w) in 40%
      propylene glycol and 60% saline (v/v). A concentration of 0.3 M [8.3% (w/v)]
      tetracaine is sufficient to reach the dose plateau. Time-response studies
      indicate that high concentrations of tetracaine in the optimum formulation [1.1
      and 1.8 M, 30 and 50% (w/v), respectively] can produce statistically significant
      analgesia relative to a placebo after 45 min. Comparison of these in vivo data
      with earlier in vitro data indicate that the optimum formulation with regard to
      clinical studies is identical to that for in vitro diffusion through hairless
      mouse skin [60% free base and 40% acid salt (w/w) in 40% propylene glycol and 60%
      saline].

PMID- 8289126
TI  - Species scaling of propafenone disposition and concentration--time relationships
      among eight mammalian species.
AB  - Usually, smaller mammals have higher clearances per unit body mass than do larger
      mammalian species. When clearance and other pharmacokinetic parameters are
      correlated with internal physiological processes, species tend to dispose of
      drugs at a similar pace. The first application of this concept is pharmacokinetic
      time, expressed with different units: Kallynochron, Apolysichron, Dienetichron,
      and Syndesichron. The present work describes pharmacokinetic time in these units
      from data obtained with propafenone in eight animal species: mouse, rat, rabbit,
      dog, sheep, human, cow, and horse. Additionally, volume of distribution (Vdss =
      6.5 B0.94) and clearance (CL = 0.17 B0.86) were correlated to body weight (B).
      Different units of pharmacokinetic time were evaluated with an Akaike Information
      Criterion test, and the Syndesichron was the unit that provided the best
      superimposition for the concentration-time plot for all animal species. It can be
      inferred that all mammalian species eliminated half of the dose from their bodies
      in 4759 Syndesichrons.

PMID- 8289127
TI  - Stability surveillance testing: an effective and efficient approach.
AB  - Stability surveillance programs are run to confirm on a regular basis the
      registered shelf-life of pharmaceutical products in relation to the relevant
      climatic zone(s). The "selected date" and the "fixed interval" procedures are
      compared with respect to their applicability for obtaining a reliable estimate of
      the true shelf-life. Advantages of the selected date over the fixed interval
      approach are (1) a more reliable estimate of the true shelf-life, and (2) a more
      efficient approach in terms of time and costs.

PMID- 8289128
TI  - Modeling of solute sorption by polyvinyl chloride plastic infusion bags.
AB  - Methods for estimating the equilibrium and time-dependent sorption of solutes by
      polymeric containers have been developed. The methods are specifically applied to
      the sorption of solutes by polyvinyl chloride (PVC) infusion bags. The methods
      correlate the partition coefficients and dissociation constant (when appropriate)
      of the solute, the physical dimensions of the container, and solution pH with
      single parameters that dictate the shape of the sorption profile. To determine
      the equilibrium sorption level for PVC containers, the fractional binding of a
      solute is correlated with its hexane-water and octanol-water partition
      coefficients. Calculations based on single partition coefficients are less
      effective in terms of mimicking the behavior of the PVC. To determine the
      sorption profile (fractional binding versus time), the partition coefficients are
      related to the fraction binding at a particular time through a single parameter
      referred to as the sorption number. Equilibrium fractional binding and sorption
      profiles for various drugs stored in PVC containers are generated with the models
      and agree well with reported behavior. The effect of pH on the sorption process
      is also examined.

PMID- 8289129
TI  - Iontophoresis of hydrocortisone across hairless mouse skin: investigation of skin
      alteration.
AB  - The effects of hydration, sodium dodecyl sulfate (SDS), and electric current on
      the permeability of hairless mouse skin was examined in vitro with a neutral
      solute, hydrocortisone, as a permeant. The study was carried out by pretreating
      the skin with (1) normal saline, (2) 0.06% SDS in 0.3% NaCl, (3) normal saline
      plus 0.5 mA anodic current, and (4) 0.06% SDS in 0.3% NaCl plus 0.5 mA anodic
      current for 8 h. The pretreated skin was then immediately used for passive or
      anodic transport of hydrocortisone. Results show that pretreatment of skin with
      either normal saline or 0.06% SDS resulted in a slightly increased passive
      penetration of hydrocortisone with a prolonged lag time, but did not
      significantly change the anodic transport of hydrocortisone. There was no
      significant difference between normal saline pretreatment and 0.06% SDS
      pretreatment, indicating that 0.06% SDS did not irreversibly alter the
      permeability of skin other than its hydration effect. Pretreatment of skin with
      current, and especially with current combined with 0.06% SDS, yielded a
      significant increase in both passive and anodic transport of hydrocortisone with
      reduced lag time, indicating that alteration of the skin structure had occurred.
      The reversibility of this alteration depends on the duration of exposure of the
      skin to the electric field. Short-term exposure (< 2 h) does not appear to change
      the permeability of skin in any significant way; long-term exposure may lead to
      slowly reversible or irreversible skin alteration.

PMID- 8289130
TI  - In vivo evaluation of controlled-release products.
AB  - A theoretical investigation has been conducted to understand the deconvolution
      method used for evaluating the in vivo release rate of an oral controlled-release
      product from the plasma drug concentration versus time profile. The theory is
      based on well-accepted pharmacokinetic compartmental models. The cumulative
      amount of drug released from a dosage form can be partitioned into two parts: the
      amount already absorbed and the amount released but still remaining at the
      absorption site in the gastrointestinal tract. The cumulative amount absorbed at
      any time, t, can be estimated from the plasma concentration versus time profile
      by the compartmental model-based Wagner-Nelson method or Loo-Riegelman method. We
      have derived a mathematical expression relating the amount at the absorption site
      with the plasma drug concentration versus time profile assuming a first-order
      absorption rate process. The difference between the in vivo release profile and
      the in vivo absorption profile is illustrated. Because what determined in vitro
      is the release profile, it should preferentially be correlated with the in vivo
      release profile, not the absorption profile. However, when absorption is much
      faster than elimination, the estimated absorption profile is a good approximation
      of the release profile. In this circumstance, it is advantageous to use
      absorption profiles to demonstrate correlation of in vitro and in vivo dosage
      form performance to avoid the noise inherent in the numerical method of deriving
      the exact in vivo release profile.

PMID- 8289131
TI  - Quantitative analysis of the lipophilic doxorubicin analogue annamycin in plasma
      and tissue samples by reversed-phase chromatography.
AB  - A rapid and sensitive HPLC method was developed to detect and quantitate the
      lipophilic doxorubicin analogue annamycin (Ann) and its metabolites in biological
      samples. Reversed-phase chromatography coupled with fluorescence detection was
      used. The emission and excitation wavelengths of the fluorescent detector were
      set at 550 and 472 nm, respectively. The optimal mobile phase was
      acetonitrile:methanol:water at a 115:95:90 ratio (v/v/v). The lower limit of
      detection was 0.35 ng of Ann (7 ng/mL). The retention times of 4
      demethoxyadriamycinone (Anone) and Ann were 2.6 and 4.3 min, respectively, and
      their resolution was 1.3. The precision of the determination of Ann and Anone
      were 0.5 +/- 0.3 and 0.8 +/- 0.7%, respectively. Ann dissolved in methanol was
      stable under the determination conditions. With chloroform, 60-90% of Ann was
      extracted from biological samples. Apart from Anone, two Ann metabolites
      (retention times 3.4 and 6.0 min) were detected in plasma and tissues from
      C57BL/6 mice bearing subcutaneous B16 tumors 6 h after intravenous administration
      of a 5-mg/kg suspension of Ann. No peaks were detected in blank tissues and
      plasma.

PMID- 8289132
TI  - Skin permeation enhancement of tegafur by ethanol/panasate 800 or ethanol/water
      binary vehicle and combined effect of fatty acids and fatty alcohols.
AB  - The effects of vehicle and enhancer on the skin permeation of tegafur across
      excised hairless mouse skin were investigated. Ethanol, water, panasate 800
      (tricaprylin), and their mixtures were used as vehicles, and then a series of
      fatty acids or fatty alcohols was employed as representative enhancers. The skin
      permeability of tegafur was dramatically increased by the combination of ethanol
      and panasate 800, whereas the combination of ethanol and water resulted in only a
      little increase. The greatest permeation ratio (56.8% of dose at 12 h) was
      obtained with the ethanol/panasate 800 (40/60) binary vehicle. Furthermore, the
      skin permeability of tegafur could be enhanced by the addition of fatty acids or
      fatty alcohols to ethanol/panasate 800 (40/60) and ethanol/water (60/40) binary
      vehicles. The infinite dose studies suggested that panasate 800 decreased the lag
      time by increasing the diffusion of tegafur, and ethanol increased the permeation
      rate by increasing the partition of tegafur into skin. The effects of fatty acids
      or fatty alcohols added to ethanol as a single vehicle were dramatic, but did not
      appear in the case of panasate 800 as a single vehicle. In conclusion, panasate
      800 was an excellent hydrophobic vehicle in that it minimized time lag and
      promoted tegafur permeability combined with ethanol. This improvement was further
      promoted when enhancers were added.

PMID- 8289133
TI  - Analysis of the particle size distribution and internal volume of liposomal
      preparations.
AB  - In this work we studied the particle size distribution of three liposomal
      preparations by quasi-elastic light scattering spectroscopy. Sized unilamellar
      vesicles of small diameter (s-SUV) were prepared by ultrasonication and
      subsequent centrifugation followed by extrusion through polycarbonate membranes
      of 0.2-micron pore size. Large unilamellar vesicles were obtained by reversed
      phase evaporation (REV) and extrusion through polycarbonate filters with or
      without preliminary freezing-thawing cycles (VETI and VETII, respectively). After
      preparation, REV were sized to small diameter REV (s-REV) by extrusion through
      0.4- and 0.2-micron polycarbonate membranes. According to the results, the s-SUV
      preparations were made up of two subpopulations, the major of which consisted of
      vesicles that were 26 nm in mean diameter and accounted for 95% of the overall s
      SUV population. The s-REV dispersions always resolved into two populations
      centered at 120 and 380 nm, the relative proportions of which depended on the
      pore size of the filters used. VET structures were composed of a single
      population of vesicles that were approximately 100 nm in mean diameter.
      Cholesterol inclusion into the bilayer composition extended the distribution
      without altering its mean value. On the other hand, the internal volumes
      calculated from mean diameters or assuming a Gaussian distribution were
      inconsistent with experimental data obtained by usual techniques.

PMID- 8289134
TI  - Nonlinear multiple-dose pharmacokinetics of the dopamine reuptake inhibitor
      vanoxerine.
AB  - The human pharmacokinetics of vanoxerine (GBR 12909) were studied in 14 normal
      subjects with a multiple-dose regimen. In a crossover design, each subject
      received daily oral doses of 25, 75, and 125 mg for 14 days at each dose level
      with washout periods of 7 days duration. Drug concentrations in serum during and
      after dosing were estimated by an HPLC method sensitive to 2 nmol/L
      (corresponding to 1.04 ng/mL). Drug accumulation was observed during dosing at
      the two highest dose levels, but near steady-state conditions were attained
      within 9-11 days of dosing. Estimates of steady-state concentrations all showed
      statistically significant deviations from dose linearity in the form of
      disproportionately higher concentrations at higher dose levels than expected from
      drug concentrations in serum at lower doses. The nonlinear pharmacokinetics was
      most likely due to increasing bioavailability with dose. The mean elimination
      half-lives were 53.5 and 66.0 h at 75 and 125 mg/day, respectively, in accordance
      with the observed time to reach near steady-state conditions. These estimates
      were higher than previous estimates in less extensive studies.

PMID- 8289135
TI  - Determination of the optimized individual kinetic constants of the aminolysis
      reaction in basic medium of beta-lactam antibiotics by a numerical computational
      method.
AB  - The individual kinetic constants of the aminolysis reaction in basic medium of
      several beta-lactam compounds (6-aminopenicillanic acid, carbenicillin, 7
      aminocephalosporanic acid, and cephalothin) are determined and improved by
      application of a computational method KINBETA. The method uses a modified version
      of the AGDC optimization algorithm adapted to the reaction system. Initial
      estimates of the constants for this reaction, obtained from the conventional
      methodology reported in the literature, were used. The computational method
      applied is self-consistent and affords both a considerable saving in experimental
      time and more reliable and exact results.

PMID- 8289136
TI  - Determination of benzalkonium chloride in ophthalmic solutions containing
      tyloxapol by solid-phase extraction and reversed-phase high-performance liquid
      chromatography.
AB  - A procedure using solid-phase extraction (Supelcoclean CN) followed by HPLC
      [Beckman Ultrasphere CN, acetonitrile:phosphate solution (60:40, v/v)] was
      developed and validated to quantitate the quaternary ammonium preservative
      benzalkonium chloride in an experimental ophthalmic formulation containing the
      polymeric material tyloxapol. This procedure makes routine determinations of
      benzalkonium chloride at concentrations of 0.0035 to 0.01% simpler than the
      traditional ion-pairing colorimetric methods. This method is quick, specific, and
      especially useful for drug product stability studies. In addition, because the
      method distinguishes each homologue, it can be extended to routinely determine
      the homologue ratio for quality control purposes.

PMID- 8289137
TI  - A Weibull distribution model for intradermal administration of ceftazidime.
AB  - The pharmacokinetics of 1 g of ceftazidime administered intradermally was studied
      in seven healthy volunteers. The objective of the present study was to find the
      most appropriate mathematical model to describe the drug intake process. The
      concentration of ceftazidime in plasma was measured by HPLC. The disposition of
      the drug was described by a one-compartment pharmacokinetic model, with drug
      intake occurring by different processes: a zero-order process due to the
      administration and a first-order intake from the injection site to the systemic
      circulation. The Weibull model was considered as an approximation of the overall
      process. The mean Weibull parameters were td (time necessary to transfer 63% of
      the administered drug into the systemic circulation) of 2.75 +/- 0.75 h, and f
      (shape) of 1.04 +/- 0.15. The mean elimination half-life was 2.0 +/- 0.4 h. The
      area under the concentration versus time curve obtained in this study (139 +/- 46
      mg.h/L) is very near to literature values reported after single intravenous doses
      of 1 g of ceftazidime, suggesting that the bioavailability of ceftazidime after
      intradermal administration may be approximately 100%. Moreover, the mean peak
      plasma concentration (37 +/- 16 mg/L) is in the same range as that reported in
      the literature after intramuscular administration of a single dose of 1 g.

PMID- 8289139
TI  - Correction factor for dissolution profile calculations.

PMID- 8289138
TI  - Transmucosal delivery of leucine enkephalin: stabilization in rabbit enzyme
      extracts and enhancement of permeation through mucosae.
AB  - Leucine enkephalin (Tyr-Gly-Gly-Phe-Leu; Leu-Enk) is a naturally occurring
      peptide that has been shown to have pain modulating properties. To evaluate the
      feasibility of using various absorptive mucosae as a route of systemic delivery,
      the stability of Leu-Enk and the effect of enzyme inhibitors (e.g., amastatin,
      EDTA, and thimerosal) on stabilization and permeation of Leu-Enk through rabbit
      mucosae in the presence of dihydrofusidates were investigated. Enzymes in the
      nasal, rectal, and vaginal mucosae were extracted and Leu-Enk (50 micrograms/mL)
      was added to each of the enzyme extracts and incubated to determine the kinetics
      and mechanism of degradation. The rate of degradation in the extracts in the
      absence of inhibitors followed the order: rectal > vaginal > nasal. Whereas EDTA
      had the best stabilizing effect on Leu-Enk, thimerosal was the best stabilizer
      for the degradation intermediates. A combination of amastatin (50 microM), EDTA
      (5 mM), and thimerosal (50 microM) had the greatest stabilizing effect on Leu-Enk
      and its degradation intermediates. For permeation studies, each mucosa was
      mounted onto a Valia-Chien permeation cell with Leu-Enk (200 micrograms/mL) in
      isotonic phosphate buffer (as donor solution). The enhancers used for the study
      were sodium tauro-dihydrofusidate (STDHF), sodium glycodihydrofusidate (SGDHF),
      and phosphato-dihydrofusidate (PHDHF). The greatest effect was achieved by PHDHF
      for all the mucosae. STDHF had a significant effect only on the rectal
      permeation, whereas SGDHF had significant effects on rectal and vaginal mucosae.
      Mechanisms by which the dihydrofusidates enhance permeating may involve micelle
      formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289140
TI  - Vertical forces and plantar pressures in selected aerobic movements versus
      walking.
AB  - Ten subjects between the ages of 19 and 29 years walked and performed four
      aerobic movements over a force and pressure platform. Peak plantar pressure and
      peak vertical force data were collected three times on the dominant leg as each
      subject performed all of the five activities. Peak vertical forces acting on the
      lower extremities for the low impact aerobic movements were significantly less
      when compared with the high impact movements. As was expected, no differences
      were found in peak vertical forces between walking and the low impact aerobic
      movements. Peak plantar pressures for walking were not significantly different
      when compared with any of the four aerobic movements studied.

PMID- 8289141
TI  - Lower extremity tennis injuries. Prevalence, etiology, and mechanism.
AB  - A retrospective investigation was undertaken to determine the prevalence of
      tennis-related lower extremity injuries in the San Francisco Bay area. A total of
      376 participants at various Bay area tennis clubs completed a questionnaire
      before registering for tournament play. The results obtained from the survey
      indicate that 91.2% of this population had an injury to the lower extremity. A
      discussion of the etiology and mechanism of the various lower extremity injuries
      is presented.

PMID- 8289142
TI  - Comparison of cotton and acrylic socks using a generic cushion sole design for
      runners.
AB  - A longitudinal single-blind study was conducted to test the friction blister
      prevention properties of synthetic acrylic socks in a generic construction. This
      study serves as a comparison with the authors' previous work comparing acrylic
      and cotton socks in a patented padded construction. Twenty-seven long-distance
      runners provided data regarding dampness, temperature, friction blister
      incidence, severity, and size. Two different socks were tested; each was
      identical in every aspect of construction except the fiber content. One test sock
      was composed of 100% synthetic acrylic fibers, and the other was composed of 100%
      natural cotton fibers. These results were unsuccessful at demonstrating any
      superiority of cotton or acrylic fibers when knitting produced a generic "cushion
      sole" sock. The superiority of acrylic fibers has thus far been demonstrated only
      when sock knitting provides adequate anatomical padding [corrected].

PMID- 8289143
TI  - Injury prediction among runners. Preliminary report on limb dominance.
AB  - A preliminary study examined the independent association of lower extremity limb
      dominance to running injuries. For the purposes of this study, limb dominance was
      recognized as an individual's ability to perform a specific skill test with
      greater accuracy, speed, and agility with one limb rather than the contralateral
      limb. Three limb dominance tests were used to identify limb dominance. The
      protocol, application, and scoring system for these screening tests are
      presented. The screening tests were sensitive and identified limb dominance among
      elite runners. No significant (P < 0.05%) association between limb dominance and
      running injuries could be confirmed by this study. These results could be an
      artifact of a small (N = 26) subject population or the elite nature of the
      subject population. Further testing and observation with a larger subject
      population are recommended.

PMID- 8289144
TI  - Use of soft heat-molded orthoses in sports. A clinical analysis.
AB  - Podiatrists have had considerable success with the use of orthoses in the
      treatment of athletic injuries and faulty biomechanics. In-office fabrication of
      soft orthoses out of heat-moldable plastics provides an alternative to the more
      rigid, prescription device. Easily constructed in 15 to 30 min, the soft heat
      molded orthoses have shown favorable results when used clinically with injured
      athletes. Although the need for more comprehensive studies exists, podiatrists
      should consider the use of soft heat-molded orthoses with their athletic patients
      and possibly in combination with the more permanent, rigid orthoses.

PMID- 8289145
TI  - Popliteus tendinitis.
AB  - Popliteus tendinitis is a relatively infrequent and often misdiagnosed injury of
      the posterior aspect of the knee. The clinical significance of this injury is
      particularly relevant to the serious runner and triathlete, as the symptoms
      resulting from this injury can be disabling.

PMID- 8289146
TI  - Ankle dorsiflexion.

PMID- 8289147
TI  - [Intracellular labeling with injection of biotinylated compounds and its
      application for analysis of neuron network].

PMID- 8289148
TI  - The two faces of Janus.

PMID- 8289149
TI  - Cardiopulmonary resuscitation: effectiveness, training and survival.

PMID- 8289150
TI  - Black looks ... back ... and ahead.

PMID- 8289151
TI  - The clinical implications of autoantibody detection in rheumatology.
AB  - The laboratory plays an increasing role in the diagnosis and clinical management
      of patients with rheumatic diseases. It is therefore essential that the results
      of laboratory tests are both accurate and reliable, and give clinicians correct
      information. It is also important to keep clinicians informed of the changes
      occurring in the rapidly evolving field of investigation of autoantibodies.

PMID- 8289152
TI  - Sleep apnoea and related conditions. Summary of a report of a working party of
      the Royal College of Physicians.

PMID- 8289153
TI  - Psoriasis and interleukin-1. A translation.

PMID- 8289154
TI  - Dysbarism: the medical problems from high and low atmospheric pressure.
AB  - The most serious problems resulting from a change in ambient pressure are
      pulmonary barotrauma with air embolism and decompression sickness. The small
      differential pressures used in ventilators at atmospheric pressure may tear lung
      tissue and, in diving, deaths have occurred from the expansion of pulmonary gas
      on an ascent of less than two metres. The bubbles of respired gas that enter the
      systemic circulation often occlude cerebral arteries and may cause infarction. In
      decompression sickness, bubbles form in the tissues from supersaturation of the
      nitrogen or helium absorbed under pressure. Joint pain--the 'bends'--is
      associated with gas in particular connective tissue. Serious decompression
      sickness results from the entry of microbubbles into the systemic veins. Large
      numbers of bubbles trapped in the lung cause an acute respiratory syndrome known
      as 'chokes'. If the lung filter is overwhelmed, or microbubbles pass into the
      systemic arteries through an atrial septal defect, they may open the blood-brain
      barrier, affecting brain and spinal cord function. Untreated, demyelination with
      relative preservation of axons may occur, the pathological hallmarks of multiple
      sclerosis. Gas bubble disease requires urgent compression in a hyperbaric chamber
      and the use of high partial pressures of oxygen.

PMID- 8289155
TI  - Hazards of air travel for the obese: Miss Pickwick and the Boeing 747.
AB  - A morbidity obese woman took a touring holiday which included two long flights
      and a stay at altitude. At the end of the second week of her holiday she was
      admitted to hospital in respiratory and cardiac failure. When she was better she
      travelled home by a combination of air ambulance and scheduled flights with a
      medical escort. This extreme case illustrates some of the physiological and
      physical challenges of air travel to the obese passenger, which may precipitate
      respiratory and cardiac decompensation in susceptible individuals. When advising
      these patients, consultation with the airline medical department is recommended,
      and preflight testing by altitude simulation may be helpful. If medical transport
      is required, there may be particular problems in lifting and accommodating these
      patients on board normal air ambulance aircraft.

PMID- 8289156
TI  - The grey area of effort syndrome and hyperventilation: from Thomas Lewis to
      today.
AB  - Lewis used the diagnosis 'effort syndrome' for subjects whose ability to make and
      sustain effort had been reduced by homeostatic failure. A major element was
      depletion of the body's capacity for buffering the acids produced by exercise. In
      his view this systems disorder was not to be regarded as a specific organ
      disease, and losing sight of the metabolic element would foster the invention of
      fanciful, unphysiological diagnoses. His views were dismissed because normal
      resting plasma bicarbonate levels were considered by others in that era to
      exclude serious depletion of the body's total capacity for buffering the effects
      of exertion. Today, effort syndrome is still a useful diagnosis for a condition
      of exhaustion and failure of performance associated with depletion of the body's
      buffering systems. Other elements associated with homeostatic failure are now
      recognised, principally emotional hyperarousal and hyperventilation. Their
      physiological interrelationships are described. Effort syndrome is amenable to
      recovery through rehabilitation, and it may be a mistake to treat chronic fatigue
      syndrome and unspecific illness without including it in the differential
      diagnosis.

PMID- 8289157
TI  - Drug selection and information: some recommendations from the World Health
      Organization.

PMID- 8289158
TI  - Safety of medicines in Europe.

PMID- 8289159
TI  - Audit in acute severe asthma--who benefits?
AB  - This paper reviews published audit activity for a single common condition
      (asthma). Has this effort brought about better care for the patient? The result
      of this audit of audits reveals that specialists do follow the guidelines on the
      management of acute asthma with good results, but that general physicians, in
      whose care perforce many acute episodes are managed, do not seem to be aware of
      the published good practice guidelines.

PMID- 8289160
TI  - Guidelines for the diagnosis, investigation and management of osteoarthritis of
      the hip and knee. Report of a Joint Working Group of the British Society for
      Rheumatology and the Research Unit of the Royal College of Physicians.
AB  - Osteoarthritis is a frequent medical problem. In general practice,
      musculoskeletal problems account for one in 10 of new consultations, 18% of them
      for osteoarthritis [1]. Many patients with osteoarthritis receive all the
      treatment they need from their general practitioner. Others require specialist
      rheumatological advice, and a few need joint replacement surgery. Guidelines for
      the care of this common problem as it affects the lower limbs will assist in the
      provision of the most appropriate care and help to identify areas where further
      research is necessary.

PMID- 8289161
TI  - Medical management of terminal illness. A statement of the Committee on Ethical
      Issues in Medicine of the Royal College of Physicians.

PMID- 8289162
TI  - The place of research in the training of NHS consultant physicians.

PMID- 8289163
TI  - The continuum of medical education. The role of basic medical sciences.

PMID- 8289164
TI  - CPR and the RCP (1). Training of doctors in NHS hospitals.
AB  - Six years after the Royal College of Physicians published its report, most
      hospitals in the UK with acute coronary beds fail to train or test their doctors
      adequately in the skills of cardiopulmonary resuscitation. Doctors want more
      training, and consultants try to give it, but there is a lack of funds for this
      basic yet critical task.

PMID- 8289165
TI  - CPR and the RCP (2). Training of students and doctors in UK medical schools.
AB  - We asked British medical schools and teaching hospitals about the training they
      offer to medical students and hospital doctors in cardiopulmonary resuscitation.
      The response rate was 96%. Training that is practical and consistent with
      guidelines is offered to nearly all students and house officers, often by
      consultants. Training for other junior doctors and consultants is much less
      common. The organisation of training is haphazard, and many hospitals have no
      resuscitation training officers. As a result, few doctors receive the frequent
      retraining needed to maintain competence in managing cardiopulmonary arrest.

PMID- 8289166
TI  - The teaching hospital and medical school AD 2010.

PMID- 8289167
TI  - The cardiac ventricular myocyte as a substrate for sudden death. The regional
      lecture in Bath 1993.

PMID- 8289168
TI  - Civil justice--some problems and possible solutions. Based on the Samuel Gee
      Lecture 1993.

PMID- 8289169
TI  - A good doctor and/or a good scientist? The medical academic's mid-life crisis.

PMID- 8289170
TI  - Hans Sloane and his friends. The FitzPatrick Lecture 1993.

PMID- 8289171
TI  - Osler's changing influence. Based on the Osler oration given at the Royal College
      of Physicians in 1990.
AB  - Over 20 years in North America William Osler transformed the pattern of medical
      education for both undergraduates and specialists. He wrote a textbook that not
      only was a stimulus to medical students and young doctors, but also inspired the
      railway baron J D Rockefeller to devote his wealth to the advancement of medical
      research and education. He encouraged the creation of medical associations and
      societies because he believed, rightly, that these enhanced not only the quality
      of medicine but also the relationship of the members of the profession, one with
      another. He provided a great library of medical history and medical biography
      which has been and will be an inspiration for years to come. In the 15 years
      Osler spent in England he created a school of medical science which has continued
      to burgeon and has formed a foundation for a great clinical and research medical
      school. He inspired the creation of the post-graduate centres associated with the
      general hospitals in every town throughout the country; he provided material for
      a biography which has inspired medical students and practitioners, who now
      realise that medicine is primarily about sick people, not disease; and he
      directed another great benefactor, Lord Nuffield, to devote his riches to many
      aspects of medicine.

PMID- 8289172
TI  - More therapeutic conservatism.

PMID- 8289173
TI  - More therapeutic conservatism.

PMID- 8289174
TI  - More therapeutic conservatism.

PMID- 8289175
TI  - More therapeutic conservatism.

PMID- 8289176
TI  - Black looks ... at habits.

PMID- 8289177
TI  - Black looks ... at habits.

PMID- 8289178
TI  - Neglecting the elderly diabetic?

PMID- 8289179
TI  - Investigation and management of stable angina.

PMID- 8289180
TI  - Investigation and management of stable angina.

PMID- 8289181
TI  - If I were a patient.

PMID- 8289182
TI  - Clinical and public health ethics.

PMID- 8289183
TI  - Synthesis and structure activity relationships of cis- and trans-2,3,4,4a,9,9a
      hexahydro-1H-indeno[2,1-c]pyridines for 5-HT receptor subtypes.
AB  - A series of cis- and trans-fused hexahydroindeno[2,1-c]pyridines have been
      prepared and evaluated for affinity and selectivity at the 5-HT1A subtype of the
      serotonin receptor. Using molecular modeling studies we predicted that the 5
      methoxy-trans-fused members of this class would exhibit affinity for this site.
      In agreement with these predictions, trans-5-methoxy-N-propyl-2,3,4,4a,9,-9a
      hexahydro-1H-indeno[2,1-c]pyridi ne (6a) demonstrated moderate affinity and high
      selectivity for the 5-HT1A binding site, whereas the cis-fused isomer 5a
      demonstrated virtually no affinity at this site. Additional trans-fused analogs
      from this series, where the nitrogen was substituted with a variety of alkylene
      imide containing appendages, demonstrated high (0.60-51 nM) affinity and
      excellent selectivity for the 5-HT1A site. Certain of these analogs, independent
      of ring-fusion stereochemistry, also demonstrated high affinity for the 5-HT2
      binding site.

PMID- 8289184
TI  - Conformational analysis of 5-lipoxygenase inhibitors: role of the substituents in
      chiral recognition and on the active conformations of the (methoxyalkyl)thiazole
      and methoxytetrahydropyran series.
AB  - The investigation of the SAR of 5-lipoxygenase (5-LO) inhibition of a series of
      racemic (methoxyalkyl)thiazoles, exemplified by compound 7 (ZM-211965), has led
      to other active, racemic derivatives in which the thiazole moiety has been
      replaced by an ester or an ether. Furthermore, the cyclization of the ethers has
      given a highly potent, but achiral series, the methoxytetrahydropyrans
      (methoxyTHP), exemplified by 41 (ZD-2138) presently under clinical evaluation.
      More recent structural investigations have led to chiral members of this series
      bearing a 2-methyl substituent in the tetrahydropyran ring. The potential for
      enantioselectivity in each of the three noncyclic, racemic series led us to
      synthesize the pure enantiomers ((R)-13c, (S)-13c, (R)-13d, (S)-13d, (R)-15c, (S)
      15c, (R)-16b, (S)-16b, and (R)-16c, (S)-16c) and to determine their absolute
      configuration. The biological activity of each enantiomer was evaluated in intact
      mouse macrophages and in human whole blood and showed that, of these three
      series, only the thiazole is enantioselective and that the active configuration
      is (S) (being between 2 and 3 orders of magnitude more potent than the (R) isomer
      in mouse macrophages). Conformational analysis using systematic conformational
      searching, molecular mechanics, and semiempirical methods has been performed on
      the chiral compounds, and the results have helped to explain the
      enantioselectivity in the thiazole series and to define the role of the
      substituents around the quaternary carbon. Simultaneously in the achiral
      tetrahydropyran (THP) series, the critical role of the methoxy substituent has
      been examined through the synthesis of the ethyl (24b), ester (22b),
      methoxymethyl ether (26), hydroxymethyl (25b), aldehyde (27b), ketone (29b),
      hydroxy (31b), and methyl (23b) analogues and by analysis of their biological and
      conformational properties. This approach, complemented by the results of a
      similar study carried out on the Z and E isomers of the chiral ethyl-2-methylTHP
      derivative (39b and 40b), has also led to the characterization of the active
      conformation in this series. The whole study has identified new elements to
      clarify the 3D structural requirements of the 5-LO active site.

PMID- 8289185
TI  - 5-Aryl-3-(alkylthio)-4H-1,2,4-triazoles as selective antagonists of strychnine
      induced convulsions and potential antispastic agents.
AB  - Selected examples from three series of isomeric (alkylthio)-1,2,4-triazoles were
      prepared and examined for anticonvulsant activity versus strychnine-, maximal
      electroshock-, pentylenetetrazole-, and 3-mercaptopropionic-acid-induced seizures
      in mice. A number of 5-aryl-3-(alkylthio)-4H-1,2,4-triazoles were selective
      antagonists of strychnine-induced convulsions. The isomeric 3-aryl-5-(alkylthio)-
      and 5-aryl-3-(alkylthio)-1H-1,2,4-triazoles were essentially inactive as
      anticonvulsants. The most potent antagonist of strychnine-induced convulsions was
      5-(2-fluorophenyl)-4-methyl-3-(methylthio)-4H-1,2,4-triazole (3s), while the most
      selective antagonist was 5-(3-fluorophenyl)-4-methyl-3-(methylsulfonyl)-4H-1,2,4
      triazole (3aa). The anticonvulsant profiles of these 4H-1,2,4-triazoles suggested
      that they were acting functionally like glycine receptor agonists. Since it has
      recently been postulated that compounds possessing glycine-agonist-like
      properties might be useful in the treatment of spasticity, we examined 5-phenyl-4
      methyl-3-(methylsulfonyl)-4H-1,2,4-triazole (3c) in an in vivo model of
      spasticity. In this regard, 3c reduced the occurrence of hyperreflexia in rats
      that had received spinal transections 5-10 weeks previously. While triazole 3c
      appeared to possess glycine-agonist-like properties in vivo, it did not displace
      [3H]strychnine binding from rat brain stem/spinal cord membranes in vitro. On the
      other hand, 3c enhanced muscimol-stimulated 36Cl influx in a rat cerebellar
      membrane preparation, indicating a possible interaction of these triazoles with
      the GABAA receptor.

PMID- 8289186
TI  - Photoactivatable 2-(4'-azidotetrafluorophenyl)-5-tert-butyl-1,3-dithiane-bis-
      sulfone and related compounds as candidate irreversible probes for the GABA-gated
      chloride channels.
AB  - Syntheses of 2-substituted photoactivatable derivatives of 5-tert-butyl-1,3
      dithiane and their oxidized bis-sulfone derivatives are described with the aim of
      developing original photoaffinity probes for the GABA-gated chloride channel.
      Diazocyclohexadienone as well as fluorinated arylazido derivatives were chosen as
      photosensitive moieties. The dithiane molecules were synthesized by condensation
      of 2-tert-butylpropane-1,3-dithiol with the appropriate substituted
      benzaldehydes. The diazocyclohexadienonyl derivatives were synthesized either by
      diazotization of the corresponding dithiane arylamine precursors (compounds 1, 2,
      17, and 18) or by diazotization of the bis-sulfone dithiane arylamine (compounds
      19 and 20). The reversible binding properties of the photosensitive probes were
      established on bovine cortex P2 membranes by displacement of [3H]-tert
      butylbicycloorthobenzoate. While the bromo-substituted diazocyclohexadienoyl
      dithiane derivatives (compounds 1 and 2) exhibited a Ki of about 2-4 microM 2-(4'
      azidotetrafluorophenyl)-5-tert-butyl-1,3-dithiane-bis-sulfon e (compound 3) gave
      a Ki of 0.2 microM. On irradiation, probe 3 produced a 25% irreversible loss of
      TBOB binding sites in brain membranes. Moreover, this loss was fully protectable
      by TBOB, demonstrating the specificity of the photochemical inactivation by
      compound 3 for the convulsant site of the GABAA receptor.

PMID- 8289187
TI  - Design of cyclic deltorphins and dermenkephalins with a disulfide bridge leads to
      analogues with high selectivity for delta-opioid receptors.
AB  - We earlier suggested that the low receptor selectivity observed for previously
      synthesized constrained analogues of deltorphin I (DT I) was the result of a
      reduction in the lipophilic surface of the C-terminal of the peptide. To confirm
      this prediction and to further test a previously proposed conformational model
      for bioactivity at delta opioid receptors, we have synthesized several new cyclic
      analogues with the general structure [D-Xaa2,Yaa5]deltorphin I and II in which
      Xaa2 is D-cysteine or D-penicillamine (D-Pen), and Yaa5 is an L- or D
      penicillamine residue. Additional substitutions at positions 4, 6, and 7 also
      were examined. The analogues were tested for binding to mu- and delta-opioid
      receptors and in mouse vas deferens and guinea pig ileum biological assays. The
      introduction of a lipophilic L-Pen in position 5 and D-Cys or D-Pen in position 2
      resulted in a highly delta-selective series of analogues, which fully confirmed
      our prediction. The cyclic analogues formula; see text: DT I are among the most
      delta-selective analogues described thus far.

PMID- 8289188
TI  - Cyclic enkephalin analogs with exceptional potency at peripheral delta opioid
      receptors.
AB  - A series of super potent and delta-opioid-receptor-selective cyclic hexapeptides
      of the general formula [formula: see text] (where X is hydrogen or halogen) has
      been synthesized. The unsubstituted hexapeptide formula; see text: [Phe6]DPLCE)
      has extremely high potency at peripheral delta opioid receptors (IC50 value in
      the MVD assay is 0.016 nM) and in bioassays is the most selective compound in
      this series. The introduction of halogens in the phenyl ring of phenylalanine at
      position 4 led to significant changes in the selectivity and affinities at
      peripheral and central opioid receptors. In the binding studies, the most potent
      compound is the p-fluoro analog, whereas the most selective analog is the p-iodo
      substituted peptide.

PMID- 8289189
TI  - Interaction of tetrahydrostilbazoles with monoamine oxidase A and B.
AB  - 1-Methyl-1,2,3,6-tetrahydrostilbazole (MTHS) and its analogs are oxidized by
      monoamine oxidase (MAO) A at slow rates comparable to that for the structurally
      similar neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, but the rates
      of oxidation by MAO B vary over a wide range depending on the structure of the
      analog. MAO A oxidation of all of the analogs yielded nonhyperbolic kinetic
      patterns, with little difference between the cis and trans isomers. In contrast
      MAO B showed hyperbolic kinetics and distinct stereoselectivity for the cis
      isomers. The corresponding pyridinium forms of trans-MTHS and its analogs were
      more potent inhibitors of MAO A (Ki values between 0.3 and 5 microM) than of MAO
      B, for which the Ki values varied greatly. The data suggest that the stringency
      of the MAO A active site for the geometry of the substrate molecule is less
      strict than that of MAO B. With MAO B, any substitution on the phenyl ring can
      lead to dramatic changes in the substrate properties which may be explained by
      the different orientation of substrate at the active site of the enzyme.
      Molecular geometry but not the effects of the substituents was shown to be an
      important factor in determining the effectiveness of substrate oxidation by MAO
      B.

PMID- 8289190
TI  - Synthesis of novel N-phosphonoalkyl dipeptide inhibitors of human collagenase.
AB  - The synthesis of a series of N-phosphonalkyl dipeptides 6 is described. Syntheses
      were devised that allowed the preparation of single diastereoisomers and the
      assignment of stereochemistry. The compounds were evaluated in vitro for their
      ability to inhibit the degradation of radiolabeled collagen by purified human
      lung fibroblast collagenase. Several of the compounds were potent collagenase
      inhibitors and were at least 10-fold more potent than their corresponding N
      carboxyalkyl analogues. Activity was lost when the phosphonic acid group
      P(O)(OH)2 was replaced by the phosphinic acid groups P(O)(H)(OH) and
      P(O)(Me)(OH). At the P1 position, (R)- or (S)-alkyl groups, especially ethyl and
      methyl (e.g., 12a,b, 52a,b, and 53a,b), or an (R)-phenethyl moiety (55a)
      conferred high potency (IC50 values in the range 0.23-0.47 microM). (S)
      Stereochemistry was preferred for the P1' isobutyl side chain. Structure-activity
      relationships were also investigated at the P2' site, and interestingly,
      compounds with basic side chains, such as the guanidine 57a, were equipotent with
      more lipophilic compounds, such as 52a. As with other series of collagenase
      inhibitors, potency was enhanced by introducing bicyclic aromatic P2'
      substituents. The most potent phosphonic acid of the series was the bicyclic
      aromatic P2' tryptophan analogue 59a (IC50 0.05 microM).

PMID- 8289191
TI  - Design and synthesis of bifunctional isothiocyanate analogs of sulforaphane:
      correlation between structure and potency as inducers of anticarcinogenic
      detoxication enzymes.
AB  - Thirty-five bifunctional isothiocyanates were synthesized as structural analogs
      of sulforaphane [(-)-1-isothiocyanato-4(R)-(methylsulfinyl)butane] that was
      recently isolated from broccoli as the principal and very potent inducer of
      detoxication (phase 2) enzymes in mouse tissues and murine hepatoma cells (Hepa
      1c1c7) in culture (Zhang, Y.; Talalay, P.; Cho, C.-G.; Posner, G.H. Proc. Natl.
      Acad. Sci. U.S.A. 1992, 89, 2399-2403). Determination of the potency of each
      analog in inducing NAD(P)H:quinone reductase, a phase 2 detoxication enzyme, has
      allowed generalizations concerning the relation of structure and activity. The
      most potent analogs were bifunctional derivatives in which the isothiocyanate
      group was separated from a methylsulfonyl or an acetyl group by three or four
      carbon atoms, and in some of which these groups were conformationally restricted.
      Among these analogs, the bicyclic ketoisothiocyanate (+/-)-exo-2-acetyl-6
      isothiocyanatonorbornane (30) was a very potent inducer (comparable to
      sulforaphane) of quinone reductase in hepatoma cells, and it also induced both
      quinone reductase and glutathione transferases in several mouse organs in vivo.
      This and related bicyclic ketoisothiocyanates represent potent phase 2 enzyme
      inducers that are relatively easily synthesized and that may be more stable
      metabolically than the natural sulfoxide sulforaphane.

PMID- 8289192
TI  - Sulfinosine congeners: synthesis and antitumor activity in mice of certain N9
      alkylpurines and purine ribonucleosides.
AB  - A number of N9-alkyl-substituted purines and purine ribonucleosides have been
      synthesized as congeners of sulfinosine and evaluated for their antileukemic
      activity in mice. NaH-mediated alkylation of 6-chloropurine (4) and 2-amino-6
      chloropurine (5) with certain alkyl bromides gave N7- and N9-alkylated
      derivatives (7a-d and 6a-d), the N9-isomer being the major product. Treatment of
      6a-d and 7a-d with thiourea furnished the corresponding 6-thio derivatives (9a-d
      and 8a-d). Amination of 9a-e with aqueous chloramine solution afforded the
      corresponding purine-6-sulfenamides (10-a-e), which on controlled oxidation with
      3-chloroperoxbenzoic acid (MCPBA) gave the respective (R,S)-9-alkylpurine-6
      sulfinamides (11a-e). A similar oxidation of 2-amino-6-(methyl/benzylthio)-9-beta
      D-ribofuranosylpurine (12a and 12b) and 2-amino-9-(2-deoxy-beta-D-erythro
      pentofuranosyl)-6- (methylthio)-purine (12c) with MCPBA gave the corresponding
      sulfoxides (13a-c), which on further oxidation furnished the respective sulfones
      (14a-c). Of the 20 compounds evaluated, six exhibited biologically significant
      anti-L1210 activity in BD2F1 mice and reduced body burdens of viable L1210 cells
      more than 90-97% by single treatment. Although compounds 9b and 9c at 44 mg and
      40 mg/kg per day x 1 showed a T/C of 147 and 149, respectively, this group of
      compounds was found to be less effective than some of the sulfur-containing drugs
      that we previously described (e.g. sulfenosine and sulfinosine).

PMID- 8289193
TI  - Novel potassium channel openers: synthesis and pharmacological evaluation of new
      N-(substituted-3-pyridyl)-N'-alkylthioureas and related compounds.
AB  - This report describes the synthesis and pharmacological evaluation of a series of
      novel potassium channel openers related to the pinacidil-type compounds.
      Thioureas, cyanoguanidines, and pyridine N-oxides were systematically evaluated
      for their effects on both the inhibition of spontaneous mechanical activity in
      rat portal vein (in vitro) and their antihypertensive activity (in vivo), and the
      structure-activity relationship for this series of compounds was discussed. Good
      correlation between in vitro and iv antihypertensive activity was observed for
      these compounds. Among them, cyanoguanidines bearing a conformationally rigid
      unit such as a norbornyl group generally possessed potent activity in both in
      vitro and in vivo studies. Especially, N-(6-amino-3-pyridyl)-N'-cyano-N"-(1
      methyl-2-norbornyl)guanidine (23d) was identified as a more potent potassium
      channel opener in vitro (EC100 = 3 x 10(-8) M) than pinacidil (EC100 = 10(-7) M).

PMID- 8289194
TI  - Glycylcyclines. 1. A new generation of potent antibacterial agents through
      modification of 9-aminotetracyclines.
AB  - This report describes the discovery of a new generation of tetracycline
      antibacterial agents, the "glycylcyclines". These agents are notable for their
      activity against a broad spectrum of tetracycline-susceptible and -resistant Gram
      negative and Gram-positive aerobic and anaerobic bacteria possessing various
      classes of tetracycline-resistant determinants [tet B (efflux), tet M (ribosomal
      protection)]. The design and synthesis of a number of 7-substituted 9-substituted
      amido 6-demethyl-6-deoxytetracyclines are described.

PMID- 8289195
TI  - Isozyme-specific glutathione-S-transferase inhibitors: design and synthesis.
AB  - Glutathione-S-transferase (GST) isozyme-selective inhibitors were designed by an
      empirically guided strategy. In the first phase, literature data were used to
      select C-terminal modifications which generated maximum variation in the
      catalytic efficiency (Vmax/Km) for glutathione (GSH) analogs used as substrates
      with different rat GSTs. Also, on the basis of literature data, the sulfhydryl
      group was functionalized with a selection of alkyl and aryl groups to maximize
      potential isozyme specificity. Affinity chromatography sorbents were prepared
      from these which showed isozyme selectivity for both rat tissue and recombinant
      human GST isozymes. Some of these compounds also showed selective inhibition of
      GST activity in catalysis of the reaction of 1-chloro-2,4-dinitrobenzene with
      GSH. In the second phase, electronic effects were explored through synthesis of
      an isostructural series of S-benzyl GSH ligands with different substituents on
      the aromatic ring. GST isozyme specificity for these ligands, measured by binding
      to derivatized sorbents, varied substantially, with hydrophobic substituents
      favoring the human GST M1a isozyme and electronegative moieties favoring GST P1.
      In the third phase, information obtained from testing both series of compounds
      was combined and used to prepare GSH analogs with chemical features responsible
      for isozyme specificity at both the C-terminus and the sulfur. This approach gave
      two new compounds which showed improved potency while still maintaining
      selectivity in the inhibition of GSTs. A detailed discussion of the logic used in
      the selection of functional groups for maximum potency and selectivity is
      included.

PMID- 8289196
TI  - New hexahydroxybiphenyl derivatives as inhibitors of protein kinase C.
AB  - We have previously shown that some ellagitannins are potent inhibitors of protein
      kinase C (PKC). On the basis of this finding, several series of
      hexahydroxybiphenyl derivatives of ellagic acid were synthesized as simple
      analogs of these ellagitannins and were evaluated for their inhibitory effect
      against PKC. Compounds 23 and 26 were found to be potent inhibitors of PKC, while
      hexakis-(benzyloxy)biphenyl derivatives exhibited weak anti-PKC activity.

PMID- 8289197
TI  - Adenosine deaminase inhibitors: synthesis and structure-activity relationships of
      2-hydroxy-3-nonyl derivatives of azoles.
AB  - A series of erythro-1-(2-hydroxy-3-nonyl)azole derivatives have been synthesized
      and evaluated for adenosine deaminase (ADA) inhibitory activity, in order to
      introduce simplifications in the ADA inhibitor erythro-9-(2-hydroxy-3
      nonyl)adenine (EHNA, 1a). The synthesis of most of the reported compounds was
      achieved by reaction of 2-bromo-3-nonanone with the suitable azole followed by
      reduction of the carbonyl group to give a diastereoisomeric mixture of N
      substituted (2-hydroxy-3-nonyl)azoles. Separation of diastereoisomers was
      achieved by HPLC or by preparative TLC plates. The results of the enzymatic test
      indicate that the nitrogen in the 3-position, and secondly, the nitrogen in the 5
      position are very important for the interaction of the azole ring with the
      inhibitory site on the enzyme. In fact, the pyrazole and the 2-substituted 1,2,3
      triazole derivatives (10 and 15, respectively) are nearly inactive, whereas the
      erythro-1-(2- hydroxy-3-nonyl)-1,2,4-triazole (18e) was the most potent ADA
      inhibitor in the series with Ki = 0.3 microM.

PMID- 8289198
TI  - A recombinant human stromelysin catalytic domain identifying tryptophan
      derivatives as human stromelysin inhibitors.
AB  - The human stromelysin catalytic domain (SCD) has been expressed in Escherichia
      coli and purified to homogeneity (Ye et al. Biochemistry 1992, 31, 11231). We
      have used this recombinant SCD for inhibitor screening and identified tryptophan
      derivatives as competitive inhibitors of SCD. Both Cbz-L-Trp-OH (1, IC50 2.5
      microM, Ki 2.1 microM) and Boc-L-Trp-OH (3, IC50 10 microM, Ki 8 microM) showed
      good inhibitory activity. Modification at the indole nitrogen with formyl or
      mesitylene-2-sulfonyl group (16, IC50 34 microM, Ki 28 microM; 17, IC50 63
      microM, Ki 52 microM) showed reduced activity. The amide Cbz-L-Trp-NH2 (13) was
      not active, but esters Cbz-L-Trp-OSu (14, IC50 13 microM, Ki 11 microM) and Boc-L
      Trp-OSu (15, IC50 102 microM, Ki 84 microM) showed activity. Aromatic amino acid
      derivatives Cbz-L-Tyr-OH (18, IC50 24 microM, Ki 20 microM) and Cbz-L-Phe-OH (26,
      IC50 40 microM, Ki 33 microM) were also active, but other amino acid derivatives
      had no activity. Although Cbz-D-Trp-OH (2, IC50 86 microM, Ki 71 microM) was
      active, the L-configuration is consistently preferred for inhibitory activity.
      Some of the SCD inhibitors were tested on full-length human stromelysin purified
      from cultured human cells, and they showed the same potency rank order. These
      results demonstrate the usefulness of recombinant DNA technology in generating
      the authentic human protein with improved properties for drug discovery.

PMID- 8289199
TI  - 6,6-Disubstituted Hex-5-enoic acid derivatives as combined thromboxane A2
      receptor antagonists and synthetase inhibitors.
AB  - A series of omega-disubstituted alkenoic acid derivatives were designed and
      synthesized as antithrombotic inhibitors of thromboxane A2 synthetase and
      thromboxane A2 receptor antagonists. Hexenoic acid derivatives with a 3-pyridyl
      group and a 4-(2-benzenesulfonamidoethyl)phenyl substituent were found to be
      optimal with regard to the dual mode of action. The most potent compound, (E)-6
      (4-(2-(((4-chlorophenyl)sulfonyl)amino)ethyl)phenyl)-6-(3-pyridyl) hex-5-enoic
      acid (36), inhibits thromboxane A2 synthetase in gel-filtered human platelets
      with an IC50 value of 4.5 +/- 0.5 nM (n = 4), whereas an inhibitory effect on
      cyclooxygenase is seen only at a much higher concentration (IC50: 240 microM).
      Radioligand-binding studies with [3H]SQ 29,548 in washed human platelets revealed
      that 36 blocks the prostaglandin H2/thromboxane A2 receptor with an IC50 of 19 +/
      5 nM (n = 5) and is therefore 85-fold more potent than another combined
      thromboxane A2 synthetase inhibitor/receptor antagonist, Ridogrel (4). Compound
      36 inhibits the collagen-induced platelet aggregation in human platelet-rich
      plasma and whole blood with an EC50 of 1 microM (Ridogrel: 16 microM) and 100 nM,
      respectively, and was selected for further development.

PMID- 8289200
TI  - The structural basis of camptothecin interactions with human serum albumin:
      impact on drug stability.
AB  - The intense intrinsic fluorescence emissions from several clinically relevant
      camptothecin drugs have been exploited in order to study the structural basis of
      drug binding to human serum albumin. Both HPLC and time-resolved fluorescence
      spectroscopic methodologies were employed to characterize the associations of
      camptothecins with HSA in phosphate-buffered saline (pH 7.4) at 37 degrees C. The
      alpha-hydroxy delta-lactone ring moiety of camptothecin (C), 10
      hydroxycamptothecin (HC), 10,11-(methylenedioxy)camptothecin (MC) and 9-chloro
      10,11-(methylenedioxy)camptothecin (CMC) was in each case observed to hydrolyze
      more rapidly and completely in the presence of HSA than in the protein's absence.
      Binding isotherms constructed by the method of fluorescence lifetime titration
      showed that HSA bound preferentially the carboxylate forms of C, HC, MC, and CMC
      over their lactone forms, thereby providing an explanation for the shift to the
      right in the lactone-carboxylate equilibrium observed for each compound upon HSA
      addition. In marked contrast, three analogues (SN-38, CPT-11, and topotecan) all
      displayed enhanced stabilities in the presence of HSA. While the lifetimes of CPT
      11, topotecan, and the carboxylate forms of both drugs were insensitive to the
      addition of HSA, the lifetimes of both SN-38 and its carboxylate form did titrate
      upon HSA addition. Analysis of binding isotherms constructed for the albumin
      interactions of SN-38 and its carboxylate form demonstrated a higher overall
      association constant for the lactone form [640 (M amino acid (aa) residues)-1]
      relative to the carboxylate form [150 (M aa)-1]. Our studies indicate that
      specific modifications at the 7- and 9-positions of the quinoline nucleus, such
      as those contained in CPT-11, topotecan, and SN-38, enhance drug stability in the
      presence of HSA. In the case of SN-38, the enhanced stability was shown to be due
      to preferential associations between the drug's lactone form and the blood
      protein.

PMID- 8289201
TI  - FTIR spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor
      agonist (U-46619), prostaglandin (PG)E2, PGD2, PGF2 alpha, prostacyclin receptor
      agonist (carbacyclin), and their related compounds in dilute CCl4 solution:
      structure-activity relationships.
AB  - FTIR spectra measurements and full optimization curve analysis of their spectra
      were done to obtain parameters of the OH and C = O stretching vibration bands for
      intramolecular hydrogen bondings in thromboxane (TX)A2 receptor partial agonist
      (CTA2), prostaglandin (PG)E2, PGD2, PGF2 alpha, prostacyclin (PGI2) receptor
      agonist (carbacyclin), and their related compounds in dilute CCl4 solutions. For
      CTA2, PGE2, PGD2, and PGF2 alpha, cyclic intramolecular hydrogen bonds involving
      a 15-membered ring similar to that observed for the TXA2 receptor agonist (U
      46619) were found between a carboxyl group of the alpha-side chain and a 15
      hydroxyl group of the omega-side chain. The arrangement of these side chains was
      P-shaped, and the percentage of the intramolecular hydrogen-bonded molecules with
      the 15-membered ring in CCl4 solution showed a high value of ca. 80% for these
      compounds. In addition, it was found that the cyclic intramolecular hydrogen
      bonds involving the 13-, 12-, and 12-membered rings in PGE2, PGD2, and PGF2
      alpha, respectively, are formed between the carboxyl group of the alpha-side
      chain and the 11-, 9-, and 9-hydroxyl groups of a cyclopentane ring,
      respectively, although the percentages of the intramolecular hydrogen-bonded
      molecules with these membered rings are very small. It was also found that the
      hydrogen bond is more easily formed in the order of the 11-, 9-, and 15-hydroxyl
      groups. For carbacyclin, the cyclic intramolecular hydrogen bond involving the 13
      membered ring was found between the carboxyl group of the alpha-side chain and
      the 11-hydroxyl group. The percentage of the intramolecular hydrogen-bonded
      molecules showed the value of 58% for carbacyclin. On the basis of information on
      the side-chain conformations in CCl4, we examined the structure-activity
      relationships for U-46619 in place of TXA2, PGE2, PGD2, PGF2 alpha, and
      carbacyclin in place of PGI2.

PMID- 8289202
TI  - Synthesis and DNA-sequence selectivity of a series of mono- and difunctional 9
      aminoacridine nitrogen mustards.
AB  - The aim of this work was to identify nitrogen mustards that would react
      selectively with DNA, particularly in G-rich regions. A series of mono- and
      difunctional nitrogen mustards was synthesized in which the (2-chloroethyl)amino
      functions were connected to the N9 of 9-aminoacridine by way of a spacer chain
      consisting of two to six methylene units. The length of the spacer chain
      connecting the alkylating and putative DNA-intercalating groups was found to
      affect the preference for the alkylation of different guanine-N7 positions in a
      DNA sequence. All of the compounds reacted preferentially at G's that are
      followed by G as do most other types of nitrogen mustards, but the degree of
      selectivity was greater. The compounds reacted at much lower concentrations than
      were required for comparable reaction by mechlorethamine (HN2), consistent with
      initial noncovalent binding to DNA prior to guanine-N7 alkylation. The degree of
      DNA-sequence selectivity increased as the spacer-chain length decreased below
      four methylene units. Most strikingly, long spacer compounds reacted strongly at
      5'-GT-3' sequences, whereas this reaction was almost completely suppressed when
      the spacer length was reduced to two or three methylenes. Mono- and difunctional
      compounds of a given spacer length showed no consistent difference in DNA
      sequence preference.

PMID- 8289203
TI  - S-glucosylated hydantoins as new antiviral agents.
AB  - S-Glycosylation took place on reaction of 5-alkylidene- and 5-arylidene-3-aryl-2
      thiohydantoins with glycosyl halides under alkaline conditions. Bisglucosylation
      also took place when N-3 unsubstituted hydantoins were reacted. The
      bisglucosylated hydantoins produced N-3 glucosylated hydantoins on treatment with
      ammonia in methanol. In antiviral studies the most active compounds against both
      HSV-1 and HSV-2 were 5-(2-thienylmethylene)-3-phenyl-2-(2,3,4,6- tetra-O-acetyl
      beta-D-glucopyranosyl)-2-thiohydantoin and 5-(2-thienylmethylene)-3-(4
      chlorophenyl)-2-(2,3,4,6-tetra-O-acety l-beta-D- glucopyranosyl)-2-thiohydantoin.

PMID- 8289204
TI  - Structure-activity studies of benzimidazole-based DNA-cleaving agents. Comparison
      of benzimidazole, pyrrolobenzimidazole, and tetrahydropyridobenzimidazole
      analogues.
AB  - The synthesis and cytotoxic properties of benzimidazole-based DNA-cleaving agents
      are presented herein. These agents include pyrrolo[1,2-a]benzimidazole (PBI),
      benzimidazole (BI), and tetrahydropyrido[1,2-a]benzimidazole (TPBI) analogues. As
      a result of these studies, it is concluded that the pyrrolo ring is not necessary
      for cytotoxicity (PBI is only slightly more cytotoxic than BI) but that
      homologation of the pyrrolo ring by one carbon results in a system, TPBI, prone
      to decomposition. Another conclusion is that the 6-aziridinyl derivative of the
      PBI system is more potent than the 7-aziridinyl derivative. Comparative studies
      with known antitumor agents revealed that the benzimidazole-based DNA-cleaving
      agents possess a unique spectrum of activity. Noteworthy observations are the
      high level of cytotoxicity against melanoma cell lines and the complete absence
      of activity against leukemia cell lines. The reductive activation and DNA
      cleavage properties of the most active analogue (BI-A) are also presented.
      Reduction of the quinone ring to the hydroquinone results in nucleophile and
      proton trapping by the aziridinyl group. Documented nucleophiles include water
      and the oxygen anion of 5'-dAMP. In addition, reduced BI-A reacts with DNA to
      form a stable adduct, which cleaves at G+A bases upon heating in basic gel
      loading solution.

PMID- 8289205
TI  - TcO(PnA.O-1-(2-nitroimidazole)) [BMS-181321], a new technetium-containing
      nitroimidazole complex for imaging hypoxia: synthesis, characterization, and
      xanthine oxidase-catalyzed reduction.
AB  - A technetium(V)oxo nitroimidazole complex that shows promise for imaging regional
      hypoxia in vivo, [BMS-181321, TcO(PnAO-1-(2-nitroimidazole))] (1) was prepared
      from 3,3,9,9-tetramethyl-1-(2-nitro-1H-imidazol-1-yl)-4,8-diazaundecane -2,10
      dione dioxime, a 2-nitroimidazole-containing derivative of propyleneamine oxime
      (PnAO). The 99Tc complex [99Tc]Oxo[[3,3,9,9-tetramethyl-1-(2-nitro-1H-imidazol-1
      yl)-4,8- diazaundecane-2,10-dione dioximato]-(3-)-N,N',N'',N''']technetium (V)
      was synthesized both from pertechnetate and [TcO(Eg)2]- (Eg = ethylene glycol). A
      new synthetic route to TcO(PnAO) (2) is also described. 99TcO(PnAO-1-(2
      nitroimidazole)) was characterized by 1H NMR, IR, and UV/vis spectroscopy, HPLC,
      FAB mass spectrometry, and X-ray crystallography. Electrochemistry of 1 reveals
      that the nitro redox chemistry found in the ligand is maintained upon
      coordination to technetium but shifts to a slightly more positive potential.
      Using chiral HPLC (Chiracel OD), 99mTc (1) was resolved into its two enantiomers.
      However, the two isomers were found to racemize quickly (t1/2 < 2 min) in the
      presence of water. Localization of 1 is believed to be mediated by enzymatically
      catalyzed reduction of the nitroimidazole group, so the in vitro reaction of
      99Tc(1) with the nitroreductase enzyme xanthine oxidase (XOD) was studied. XOD
      catalyzed the quantitative reduction of the nitroimidazole group on the molecule
      under anaerobic conditions in the presence of hypoxanthine. No reaction was noted
      using a non-nitro-containing complex (2). The rate of reduction of the Tc
      nitroimidazole complex (1.5 +/- 0.16 nmol/min per unit XOD) was faster than that
      observed previously for the nitroimidazole BATOs (BATO = boronic acid adduct of
      technetium dioxime) and was about two-thirds that of fluoromisonidazole, a
      compound that has proven useful for imaging hypoxia in humans when labeled with
      18F. These data suggest that BMS-181321 (1) has the potential to be recognized by
      nitroreductase enzymes in vivo, thus satisfying one of the criteria required for
      this potential hypoxia imaging agent.

PMID- 8289206
TI  - Enhancement of iron excretion via monoanionic 3-hydroxypyrid-4-ones.
AB  - The ability of 3-hydroxypyrid-4-ones bearing either a carboxylic acid or sulfonic
      acid group to mobilize iron into the bile and urine of normal rats has been
      examined and compared with that produced by 1,2-dimethyl-3-hydroxypyrid-4-one
      (L1). The compounds tested were 3-hydroxy-1-methyl-4-oxopyridine-6-carboxylic
      acid and 1-[3-hydroxy-6-(hydroxymethyl)-4-oxopyridyl]-2-ethanesulfonic acid,
      whose synthesis, biological activity, and X-ray crystallographic properties are
      described. Although estimates of activity, based on polarity and membrane
      permeability, predict such compounds to be ineffective, they were found to have
      an iron-mobilizing ability similar to that of the compounds which do not bear any
      charge at physiological pH when given parenterally. When given orally, the 3
      hydroxypyrid-4-one containing a carboxylate group enhanced the urinary excretion
      of iron, while the sulfonate analog did not substantially increase the excretion
      of iron in the urine relative to the controls. The results obtained here suggest
      that the previous emphasis on the preparation of 3-hydroxypyrid-4-ones that are
      electrically neutral at physiological pH is unnecessarily restrictive and that
      the presence of an appropriate group bearing a single negative charge is
      consistent with a high level of activity. It is proposed that such negatively
      charged molecules may gain access to the interior of cells in both the kidney and
      the liver via monoanionic transport systems. Such compounds may prove to be less
      toxic than the neutral 3-hydroxypyrid-4-ones.

PMID- 8289208
TI  - Bacterial typing systems: the way ahead.

PMID- 8289207
TI  - Mixed 5-HT1A/D-2 activity of a new model of arylpiperazines: 1-aryl-4-[3-(1,2
      dihydronaphthalen-4-yl)-n-propyl]piperazines. 1. Synthesis and structure-activity
      relationships.
AB  - A new model of 4-alkyl-1-arylpiperazines containing a terminal dihydronaphthalene
      fragment on the alkyl chain was synthesized in order to have mixed serotonergic
      and dopaminergic activity and to pursue the recent alternative approaches to the
      discovery of novel antipsychotic and anxiolytic agents. Title compounds were
      evaluated for in vitro activity on dopamine D-2 and serotonin 5-HT1A and 5-HT2
      receptors by radioreceptor binding assays. They show high nanomolar affinity for
      5-HT1A, moderate affinity for D-2, and low affinity for 5-HT2 receptors, and in
      particular, two compounds, 4-[3-(1,2-dihydro-6-methoxynaphthalen-4-yl)-n-propyl]
      1-(2- methoxyphenyl)piperazine (8) and 4-[3-(1,2-dihydro-8-methoxynaphthalen-4
      yl)-n-propyl]-1-(2- pyridyl)piperazine (15), show values (nM) of IC50 = 2.0 and
      1.4 for 5-HT1A and IC50 = 90.6 and 119.3 for D-2, respectively. Some in vivo
      behavioral studies show compound 8 to be an antagonist on 5-HT1A receptors. These
      first findings place the new arylpiperazines on the same level as that of the
      azaspirone class, e.g., 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)-n
      butyl]piperazine (NAN-190) and buspirone.

PMID- 8289209
TI  - A study of the aetiological agents of childhood diarrhoea in Lagos, Nigeria.
AB  - From December 1989 to May 1990, 315 faecal samples from children under 5 years
      old with diarrhoea (215) and without diarrhoea (100) seen at paediatric clinics
      were investigated for bacterial, viral and parasitic enteropathogens. Standard
      and recently described methods were used for the investigations, which revealed
      that 74.9% of children with diarrhoea were infected with enteropathogens compared
      with 28% of controls. In the diarrhoeal group, 59.1% had a bacterial, 26.5% a
      viral and 2.3% a parasitic aetiology. Rotavirus was the pathogen most frequently
      detected, accounting for 22.3% of positive findings in the group with diarrhoea
      versus 9% in the control group. Other important agents were: enterotoxigenic
      Escherichia coli (ETEC) (14.4 versus 6%), enteropathogenic E. coli (EPEC) (10.7
      versus 5%), enteroadherent E. coli (EAEC) (9.3 versus 4%), enterohaemorrhagic E.
      coli (EHEC) (5.1 versus 3%) and Salmonella spp. (3.3 versus 1%). The following
      enteropathogens were detected exclusively in the diarrhoeal stools: Shigella spp.
      (5.1%), Yersinia enterocolitica (0.9%), Aeromonas hydrophila (1.4%), Entamoeba
      histolytica (0.5%), Giardia lamblia (0.5%), Trichomonas hominis (0.5) and
      Trichuris trichiura (0.9%). The detection rates of rotavirus, EPEC and EAEC were
      much greater in the diarrhoeal than in the control patients. No Vibrio cholerae,
      enteroinvasive E. coli (EIEC), Plesiomonas spp. or Cryptosporidium spp. were
      detected in this study. Our data suggest that both the traditional and newly
      recognised diarrhoeal agents are important causes of diarrhoea in the children
      under 5 years old in Lagos, Nigeria.

PMID- 8289210
TI  - Antibiotic-induced release of endotoxin from bacteria in vitro.
AB  - The ability of cefotaxime, ciprofloxacin, piperacillin and tobramycin to cause
      release of endotoxin was examined in vitro with cultures of Enterobacter cloacae
      and Escherichia coli. Endotoxin was measured by a quantitative limulus amoebocyte
      lysate assay and its presence was confirmed by silver staining of the
      lipopolysaccharide moiety following SDS-PAGE. The morphology of the bacteria
      during antibiotic exposure was examined by scanning electronmicroscopy.
      Cefotaxime, ciprofloxacin and piperacillin caused significant endotoxin release,
      correlating with their ability to affect cell-wall morphology, causing
      filamentation, wall breakage and cell lysis. In contrast, little endotoxin was
      released when bacteria were exposed to tobramycin and no morphological changes
      were observed when bacteria were exposed to bactericidal concentrations of this
      aminoglycoside. Its antimicrobial spectrum and bactericidal activity make
      tobramycin an appropriate agent for treatment of sepsis caused by gram-negative
      bacteria and its lack of propensity to elicit excessive release of endotoxin may
      avoid exacerbation of endotoxin-related shock in sepsis.

PMID- 8289211
TI  - Escherichia coli O157 infections in Scotland.

PMID- 8289212
TI  - The use of gene probes, immunoassays and tissue culture for the detection of
      toxin in Vibrio cholerae non-O1.
AB  - Vibrio cholerae non-O1 strains were screened for the presence of cholera
      enterotoxin (CT) genes by means of digoxigenin-labelled polynucleotide CTA and
      CTB probes. In-vitro production of CT was investigated by the Y1 mouse adrenal
      cell assay, enzyme-linked immunosorbent assay (ELISA) and a commercial, reversed
      passive latex agglutination (RPLA) kit. Only two (0.25%) of 790 strains tested
      gave positive results with the CTA and CTB probes. The production of other
      bacterial cytotoxin(s) made it impossible to use the characteristic cell-rounding
      effect on Y1 cells for the detection of CT. CT production by the probe-positive
      strains was confirmed by the immunoassays. Two hundred and fifty-two of the 788
      probe-negative strains were tested by both cell assay and immunoassays. Of these,
      90% produced cytotoxin(s) in the cell assay. In addition, 37% gave positive
      results in CT-ELISA, but negative results with LT-ELISA and VET-RPLA. These
      results indicate the presumed presence of a toxin in V. cholerae non-O1 that is
      able to bind GM1 and react with antisera to CT, but which is not identical to CT.

PMID- 8289213
TI  - Attachment of staphylococci to different plastic tubes in vitro.
AB  - Adherence of 18 staphylococcal strains to 13 types of uncoated plastic tubes made
      from 10 different plastic materials were investigated by binding of radiolabelled
      bacteria in phosphate-buffered saline for 2 h at 37 degrees C. The different
      materials could be divided into five groups based on their ability to bind
      staphylococci. Lowest adhesion was found for plasticised polyvinylchloride.
      Simple assays for the relative binding of peroxidase-labelled human IgG or
      fibrinogen did not predict the result of adhesion studies. Neither bacterial
      surface hydrophobicity measured in a two-phase partitioning assay, nor
      hydrophobicity of materials (wettability) as measured by their contact angles in
      water correlated with bacterial adhesion. Adhesion of staphylococci to certain
      plastic materials was greatly influenced by the method used for sterilisation of
      the material.

PMID- 8289214
TI  - Activity of eight antibacterial agents on Staphylococcus epidermidis attached to
      Teflon catheters.
AB  - The presence of a Teflon catheter had no effect on the in-vitro activity of a
      range of antibacterial agents against slime producing and non-producing
      Staphylococcus epidermidis strains as determined by a microdilution assay. The
      susceptibility of S. epidermidis attached to Teflon catheters for 6, 24 and 48 h
      was also evaluated. MICs for planktonic and attached bacteria were similar. When
      bacteria attached to Teflon for 6 h were used as inocula, MBC values increased 32
      8192-fold for the antibacterial agents tested. Similar results were observed when
      bacteria attached for 24 and 48 h were used as inocula. The activity of a high
      concentration (16 x MBC) of these antimicrobial agents against S. epidermidis
      biofilms in Teflon catheters was evaluated; for five slime non-producing strains,
      the highest reduction (around 99%) in bacterial viability was produced by
      cloxacillin and teicoplanin; for the slime producers, the highest effect (99.5%
      reduction) was shown by amikacin, clindamycin cloxacillin and ciprofloxacin but
      all cases still showed bacterial counts higher than 10(3) cfu/catheter segment.
      It is concluded that adherence of S. epidermidis to Teflon catheters decreases
      the bactericidal activity of the antibacterial agents tested in vitro.

PMID- 8289215
TI  - Adhesion to and invasion of human colon carcinoma Caco-2 cells by Aeromonas
      strains.
AB  - The enteropathogenicity of Aeromonas strains that showed mannose-resistant
      adhesion to INT407 cells was evaluated by infecting Caco-2 cells and observing
      them by light and electronmicroscopy. Five of six strains adhered in large
      numbers to Caco-2 cells in the presence of mannose and caused cytopathic effects.
      Two strains of Aeromonas spp. seemed to invade Caco-2 cells, as membrane-bound
      bacteria were seen within the cytoplasm of these cells; however, staining by
      acridine orange-crystal violet appeared to show intracellular fluorescent
      bacteria in three strains. Fimbriae did not appear to play an important role in
      adhesion because fimbrial structures were not seen by transmission
      electronmicroscopy. Adhesion of four strains was inhibited by the addition of L
      fucose. The strains were negative in the fluorescence actin staining test, which
      in enteropathogenic Escherichia coli strains correlates with the ability to
      attach and efface intestinal microvilli. The DNA of the Aeromonas strains did not
      hybridise with the E. coli eae and ipaB probes, associated with attaching and
      effacing ability and invasion, respectively. These results give support to the
      enteropathogenicity of adhesive strains of Aeromonas spp., although the
      mechanisms of adhesion, and possibly invasion, remain to be elucidated.

PMID- 8289216
TI  - Outer membrane antigens of oral Treponema species.
AB  - Outer membrane (OM) antigens of several oral treponemes were studied. SDS-PAGE
      revealed a 56-58-kDa protein as a major component of isolated OM vesicles.
      Immunoblot analysis with eluted antibodies prepared from Treponema denticola ATCC
      33520 recognised the 56-58-kDa protein, which was highly conserved in the 17 T.
      denticola strains tested. The protein was also a component of a T. denticola
      desoxycholate-extractable, ethanol-soluble antigen (DES-Ag) but was not present
      in T. pectinovorum or T. vincentii ATCC 35580 and strain N9 whole-cell lysates.
      Electronmicroscopy of OM vesicles showed typical treponemal ultrastructure.
      Immunogold labelling of T. denticola ATCC 33520 with T. denticola ATCC 33520
      specific eluted antibodies recognised only the OM surface of the cell. These
      results suggest that the 56-58-kDa antigen comprises surface-orientated epitopes
      and that this antigen may be specific for T. denticola.

PMID- 8289217
TI  - Immunohistochemical distribution of leucocyte antigens in lymphoid tissues of
      cynomolgus monkeys (Macaca fascicularis).
AB  - Crossreactivity of antibodies to human leucocyte antigens with lymphoid tissues
      of cynomolgus monkeys was studied by immunohistochemistry and immunoblotting. Of
      a total of 54 clusters of differentiation (CD) antigens, 39 were expressed
      essentially with the same immunostaining patterns in the monkey as in human
      lymphoid tissues. By immunoblotting L26 (CD20) detected a 35 Kd molecule in the
      monkey lymph node. Our observations indicated that most of the CD antigens are
      expressed and can be studied in lymphoid tissues of cynomolgus monkeys.

PMID- 8289218
TI  - Vulnerability of placental antibody transfer and fetal complement synthesis to
      disturbance of the pregnant monkey.
AB  - Maternal and fetal/infant antibody levels were assessed across pregnancy and at
      birth to evaluate the prenatal transmission of IgG in the rhesus monkey. Although
      some antibody was evident in the fetus by midpregnancy, the marked increase in
      IgG occurred primarily during the last two weeks of pregnancy. This delay until
      the end of pregnancy would result in low antibody titers in premature infants. In
      contrast, when gestation length was normal, the placental transfer of IgG was
      resistant to both dexamethasone treatment and a prolonged period of stress during
      pregnancy. This resiliency occurred despite an effect of prenatal stress on other
      aspects of infant development, including physical growth and the fetal synthesis
      of complement proteins.

PMID- 8289219
TI  - Enzyme immunoassays for ovarian steroid metabolites in the urine of Macaca
      fascicularis.
AB  - In vivo studies using carbon 14 labeled estradiol (E2) and progesterone (Po) were
      performed to characterize the time course and metabolic fate of circulating E2
      and Po. Co-chromatography of human, orangutan, and macaque luteal phase urine
      samples demonstrated the presence of a steroid conjugate peak in all three
      species that was identified as being androsterone and etiocholanolone
      glucuronides. An enzyme immunoassay for urinary metabolites of Po was developed
      subsequently for Macaca spp. using a monoclonal antibody that cross-reacted with
      both C-19 and C-21 metabolites.

PMID- 8289220
TI  - Arthritis of the spondyloarthropathy variety in Callithrix jacchus.
AB  - Sixty skeletons of Callithrix jacchus were examined to identify
      spondyloarthropathy. Erosive disease in Callithrix was confirmed as
      spondyloarthropathy on the basis of diagnostic sacroiliac erosions, syndesmophyte
      formation, and the nature and distribution of the peripheral joint erosions.

PMID- 8289221
TI  - Hypertrichosis in a gibbon (Hylobates muelleri).
AB  - A case of facial hypertrichosis in a museum specimen of a Bornean gibbon
      (Hylobates muelleri) is described. Apparently, hypertrichosis has not previously
      been reported to occur in nonhuman primates. Similar pathological conditions are
      known to occur in humans, but it is unknown whether any of the numerous forms of
      human hypertrichosis is equivalent to this case in gibbons.

PMID- 8289222
TI  - Estradiol, progesterone, and sex hormone-binding globulin in female rhesus
      monkeys (Macaca mulatta).
AB  - We measured the concentrations of estradiol, progesterone, and the sex hormone
      binding globulin capacity (rhSHBG) in serum of female rhesus monkeys (Macaca
      mulatta). Although the serum rhSHBG capacity was altered by the removal of
      ovarian hormones, presumably estradiol, acute changes in serum estradiol and
      progesterone did not influence SHBG capacity. There appears to be a relatively
      low threshold for the effect of estradiol on rhSHBG capacity. The threshold must
      be present for a finite length of time to have that effect.

PMID- 8289223
TI  - Spermatogenesis and hormone levels in rhesus macaques inoculated with simian
      immunodeficiency virus.
AB  - The presence of sperm in testicular tissue of rhesus macaques that died as a
      result of infection with simian immunodeficiency virus (SIV) was related to age
      and body weight. Depressed testosterone levels were not associated with elevated
      LH levels. The data suggest that azoospermia in the SIV-infected macaques was due
      to cachexia and not a direct effect of virus on the testis, supporting a similar
      hypothesis regarding azoospermia in men infected with human immunodeficiency
      virus.

PMID- 8289224
TI  - Spatial distribution of curve length: concept and estimation.
AB  - The length of a curvilinear feature, such as a dendrite tree of a neuron, can, in
      principle, be estimated by the recent, non-invasive method of total vertical
      projections (TVPs). Curve length is a measure of size, but it reports nothing
      about curve shape. The shape of a tree-like structure can be described to some
      extent by the distribution of branch length in properly defined regions of three
      dimensional (3-D) space. A definition of curve length distribution in three
      dimensions is proposed and implemented here on a human neuron. The relevant 3-D
      regions overlap after projection, and therefore the TVPs method cannot be used
      directly to estimate the corresponding feature lengths. However, using the
      ANALYZE software system running on a SUN SPARC workstation, dendrite subsets
      sitting in predefined regions of space were rendered in different colours and
      measured separately by the TVPs method using a cycloid test system. In
      combination with non-invasive image acquisition and processing techniques, the
      length distribution concept is likely to be useful in the metrical analysis of
      either microscopic or macroscopic arborizations in a wide variety of contexts,
      including living cells and organisms.

PMID- 8289225
TI  - Quantitative acoustic microscopy of individual living human cells.
AB  - The elastic properties of cells can be measured with microscopic resolution by
      acoustic microscopy. By measuring the waveform of very short pulses, the
      thickness, and the acoustic velocity, impedance and attenuation can be determined
      from the two separate signals reflected from the top and the bottom of the cell.

PMID- 8289226
TI  - Image sharpness and contrast transfer in coherent confocal microscopy.
AB  - Confocal microscopes provide clear, thin optical sections with little disturbance
      from regions of the specimen that are not in focus. In addition, they appear to
      provide somewhat greater lateral and axial image resolution than with non
      confocal microscope optics. To address the question of resolution and contrast
      transfer of light microscopes, a new test slide that enables the direct
      measurement of the contrast transfer characteristics (CTC) of microscope optics
      at the highest numerical aperature has been developed. With this new test slide,
      the performance of a confocal scanning laser microscope operating in the confocal
      reflection mode and the non-confocal transmission mode was examined. The CTC
      curves show that the confocal instrument maintains exceptionally high contrast
      (up to twice that with non-confocal optics) as the dimension of the object
      approaches the diffraction limit of resolution; at these dimensions, image detail
      is lost with non-confocal microscopes owing to a progressive loss of image
      contrast. Furthermore, we have calculated theoretical CTC curves by modelling the
      confocal and non-confocal imaging modes using discrete Fourier analysis. The
      close agreement between the theoretical and experimental CTC curves supports the
      earlier prediction that the coherent confocal and the incoherent non-confocal
      imaging mode have the same limit of resolution (defined here as the inverse of
      the spatial frequency at which the contrast transfer converges to zero). The
      apparently greater image resolution of the coherent confocal optics is a
      consequence of the improved contrast transfer at spacings which are close to the
      resolution limit.

PMID- 8289227
TI  - A light-emitting diode light standard for photo- and videomicroscopy.
AB  - A light calibration system consisting of a compact light-emitting diode (LED)
      source with feedback control of intensity is described. The source is positioned
      in the focal plane of the microscope objective and produces flat-field
      illumination of up to 31 microW. The source can be easily used to determine the
      performance of microscope optics and camera response. It can also be used as a
      standard light source for calibration of experimental systems. Selectable light
      intensities are produced by controlling the LED input power via a feedback
      circuit consisting of a photodiode that detects output light intensity. Spectral
      coverage extends between 550 and 670 nm using green, yellow and red LEDs mounted
      side by side, which are selected individually. The LED chips are encapsulated in
      plastic diffusers which homogenize the light, and a flat field of illumination is
      obtained through a thin 1-mm-diameter aperture positioned directly over each
      chip. Provision is made for insertion of Ronchi rulings over the aperture to
      enable measurements of contrast modulation in a uniform field. The light may be
      pulse-modulated to assess camera response times and the device can be
      synchronized with video frames. Narrow bandpass interference filters can be
      placed between the objective lens and the LED source to produce monochromatic
      light without affecting the spacing of controlled light intensities since
      emission spectra do not shift appreciably over the range of LED powers chosen in
      this design. Results of tests using controlled light intensity and uniform
      illumination are presented.

PMID- 8289228
TI  - Video camera calibration for optical densitometry.
AB  - An efficient technique for calibrating video cameras to record optical density
      (OD) from microscopic images is described. The method corrects for variation over
      the field of the brightfield and darkfield intensities, does not assume a linear
      response of the camera to the incident intensity and requires a single
      calibration filter.

PMID- 8289229
TI  - Empirically determined freezing time for quick-freezing with a liquid-nitrogen
      cooled copper block.
AB  - A method is presented to determine freezing time empirically. The method is based
      on determining the amount of stretch of a skinned muscle fibre while it is being
      frozen. Freezing time, as determined with this method lies in between 0.5 and 1.5
      ms.

PMID- 8289230
TI  - The effect of soft X-radiation on myofibrils.
AB  - Myofibrils, the contractile organelles from striated muscles, have been examined
      in the X-ray microscope to determine the effect of radiation on their function
      and structure. Using X-rays of energy 350-385 eV in the water window we find that
      after an exposure to 7.5 x 10(5) photons/micron2 (calculated to give an absorbed
      dose of 20,000 Gy) the myofibrils will no longer contract. The use of the free
      radical scavenging agent, DMSO, gives some protection to the fibrils. It has also
      been found that after this much irradiation the fibrils lose up to 20% of their
      mass. Further substantial mass loss occurs on subsequent irradiation. After 25
      times the loss-of-function exposure only 30% of the mass remains. Analysis of a
      series of images of the same myofibril covering this range of exposures shows
      that the mass is preferentially lost in some areas of the structure and
      consequently significant structural changes occur.

PMID- 8289231
TI  - High-spatial-resolution maps of sulphur from human hair sections: an EELS study.
AB  - High-resolution sulphur maps have been acquired from human hair using a Zeiss CEM
      902A transmission electron microscope equipped with an energy filter. Analysis by
      electron energy-loss spectroscopy (EELS) was performed on ultrathin sections of
      hair shafts embedded in three different types of resin: Nanoplast (water
      soluble), Spurr (epoxy) and Lowicryl (low-temperature resin). Good-quality energy
      loss images have been obtained with the three resins, although it was found that
      Nanoplast gave the best image contrast. For the first time, the results obtained
      for the detection of sulphur by silver staining of hair sections, which until now
      has been the only way to map sulphur at the electron microscopic level, have been
      confirmed. The results are compared with local sulphur concentrations from bulk
      analysis.

PMID- 8289232
TI  - Improvements in the technique of vascular perfusion-fixation employing a
      fluorocarbon-containing perfusate and a peristaltic pump controlled by pressure
      feedback.
AB  - A new improved technique for whole-body perfusion-fixation of rats and other
      small animals is described. The driving force is a peristaltic pump which is
      feedback regulated by a pressure transducer that monitors the blood-perfusion
      pressure in the left ventricle of the heart. The primary perfusate-fixative is
      composed of a blood substitute--13.3% oxygenated fluorocarbon FC-75--in 0.05 M
      cacodylate buffer (pH 7.4) with a 2% glutaraldehyde. The secondary perfusate
      fixative is composed of 2% glutaraldehyde in 0.05 M cacodylate buffer (pH 7.4)
      with 20 mM CaCl2. A double-barrelled, self-holding cannula is used to cannulate
      the heart; the outer and inner barrels of the cannula are connected to the
      peristaltic pump and to the pressure transducer, respectively. The tissue oxygen
      tension in the rat is monitored by a subcutaneous oxygen electrode. Measurements
      showed that tissue hypoxia/anoxia did not develop before or during the perfusion
      fixation. Thus, the technique permits study of specimens which do not exhibit
      fixation gradients and do not contain cells fixed in a state of asphyxia. This is
      substantiated by electron micrographs of cells from different organs, revealing
      new fine structural elements. By adding oxygenated fluorocarbon to glutaraldehyde
      perfusate-fixatives, enough oxygen is made accessible for cellular respiration as
      well as for the oxygen-consuming chemical reactions of glutaraldehyde with the
      tissue. Data on anaesthesia, operative manoeuvres, mechanical components of the
      system, preparation of fixatives and flow of the perfusate-fixatives are
      furnished and discussed.

PMID- 8289233
TI  - Remapping disparate images for coincidence.
AB  - With the development of complex multimode computerized microscope systems, it is
      possible and necessary to obtain images of the same area of the microscopical
      preparation by several methods of microscopy, such as differential interference
      contrast, reflection interference microscopy, several wavelengths of fluorescence
      microscopy, laser scanning and confocal modes. Thus, varied information may be
      obtained about a single field, in the form of a set of images, taken at different
      ports of the microscope, using different digitizing cameras, each appropriate to
      certain tasks. For comparative purposes, the images should be superimposable,
      pixel by pixel, but in general they are not--they differ in image shape and size,
      magnification, distortion, centration and orientation. This paper shows how the
      problem may be approached, using an extension of the remapping procedures
      described in a previous paper, in which images of a separate grid reference slide
      are used to detect, quantify and correct the image errors. Affine remapping,
      without the use of grid images, is also described.

PMID- 8289234
TI  - Simplified nerve cell counting in the rat brainstem with the physical disector
      using a drawing-microscope.
AB  - A simple modification of the physical disector is presented which is used to
      count the number of neurons in the hypoglossal nucleus of the rat in a series of
      paraffin sections. One disector consists of two adjacent sections (6 microm
      thick) that have been Nissl-stained with cresyl fast violet. In the first step of
      the procedure each of the two sections in investigated separately with a drawing
      microscope. The boundary of the hypoglossal nucleus and the position of neurons
      devoid of, or containing a part of, the cell nucleus in the plane of the section
      are marked on transparent paper. In the second step, these two drawings are
      placed one upon another, aligned and the number of cell profiles that show a cell
      nucleus in one but not in both drawings counted. This modification of the
      disector method for cell counting needs no specialized equipment, simply a light
      microscope with drawing apparatus, and can be combined with histochemical studies
      of other sections from the same tissue block.

PMID- 8289235
TI  - Sequence alignment and penalty choice. Review of concepts, case studies and
      implications.
AB  - Alignment algorithms to compare DNA or amino acid sequences are widely used tools
      in molecular biology. The algorithms depend on the setting of various parameters,
      most notably gap penalties. The effect that such parameters have on the resulting
      alignments is still poorly understood. This paper begins by reviewing two recent
      advances in algorithms and probability that enable us to take a new approach to
      this question. The first tool we introduce is a newly developed method to
      delineate efficiently all optimal alignments arising under all choices of
      parameters. The second tool comprises insights into the statistical behavior of
      optimal alignment scores. From this we gain a better understanding of the
      dependence of alignments on parameters in general. We propose novel criteria to
      detect biologically good alignments and highlight some specific features about
      the interaction between similarity matrices and gap penalties. To illustrate our
      analysis we present a detailed study of the comparison of two immunoglobulin
      sequences.

PMID- 8289236
TI  - Post-transcriptional regulation of the str operon in Escherichia coli. Structural
      and mutational analysis of the target site for translational repressor S7.
AB  - In the Escherichia coli str operon, translation of the S12 and S7 genes is
      largely coupled, and the translational repressor S7 inhibits S7 translation,
      which is coupled to that of S12, but does not inhibit independent translation of
      S7 by free ribosomes in the intracellular pool. We have studied the S12-S7
      intercistronic region of mRNA by analyzing RNA synthesized in vitro using
      structure-specific nucleases and a chemical probe, dimethyl sulfate. Based on the
      results obtained, we have deduced a secondary structure model of the S12-S7
      intercistronic region and identified nucleotide residues "protected" by S7. We
      then carried out site-directed mutagenesis to identify nucleotide residues
      important for S7 translation as well as for repression by S7. The results showed
      that two distinct regions are important for S7-mediated repression; one is the S7
      binding region identified by the protection analysis and the second is the stem
      structure that sequesters the Shine-Dalgarno sequence for the S7 gene. Some of
      the base alterations in the first region abolished S7 binding and, as a
      consequence, abolished S7-mediated repression, without affecting the efficiency
      of S7 translation. Other mutations disrupting the stem structure in the second
      region abolished S7-mediated repression without significantly affecting the S7
      mRNA interaction. We also found that certain mutations drastically decrease S7
      translation achieved by translational coupling without affecting S7 translation
      achieved by independent initiation. These mutations are in base-paired regions
      and evidence was obtained to suggest that these base-paired structures are
      important for translational coupling. We suggest that some specific RNA
      structures in the intercistronic region play an active role in achieving
      translational coupling in this system, and that repression of S7 translation by
      S7 protein is due to disruption of such structures induced by binding of S7
      protein to the target site, rendering translational coupling very inefficient,
      but leaving independent translation initiation unaffected.

PMID- 8289237
TI  - Redefining the goals of protein secondary structure prediction.
AB  - Secondary structure prediction recently has surpassed the 70% level of average
      accuracy, evaluated on the single residue states helix, strand and loop (Q3). But
      the ultimate goal is reliable prediction of tertiary (three-dimensional, 3D)
      structure, not 100% single residue accuracy for secondary structure. A comparison
      of pairs of structurally homologous proteins with divergent sequences reveals
      that considerable variation in the position and length of secondary structure
      segments can be accommodated within the same 3D fold. It is therefore sufficient
      to predict the approximate location of helix, strand, turn and loop segments,
      provided they are compatible with the formation of 3D structure. Accordingly, we
      define here a measure of segment overlap (Sov) that is somewhat insensitive to
      small variations in secondary structure assignments. The new segment overlap
      measure ranges from an ignorance level of 37% (random protein pairs) via a
      current level of 72% for a prediction method based on sequence profile input to
      neural networks (PHD) to an average 90% level for homologous protein pairs. We
      conclude that the highest scores one can reasonably expect for secondary
      structure prediction are a single residue accuracy of Q3 > 85% and a fractional
      segment overlap of Sov > 90%.

PMID- 8289238
TI  - Selective perturbation of G530 of 16 S rRNA by translational miscoding agents and
      a streptomycin-dependence mutation in protein S12.
AB  - Previous studies have shown that a concise set of universally conserved bases in
      16 S rRNA are strongly protected from attack by chemical probes when tRNA is
      bound specifically to the ribosomal A site. Two of these bases, A1492 and A1493,
      are located in the cleft of the 30 S subunit, the site of codon-anticodon
      interaction. A third residue, G530, is located within the highly conserved 530
      stem-loop, a region that is involved in interactions with proteins S4 and S12,
      mutations in which perturb the translational error frequency. The 530 loop is
      also thought to be located at or near the site of interaction of elongation
      factor Tu on the 30 S subunit, a location that is distinct from the decoding
      site. This study monitors the response of these two A-site-related regions of 16
      S rRNA to a variety of translational miscoding agents. Several of these agents,
      including streptomycin, neomycin and ethanol, selectively potentiate tRNA
      dependent protection of residue G530 from kethoxal modification; in contrast,
      little change in reactivity of residues A1492 and A1493 is observed. These
      results are consistent with the previously demonstrated importance of G530 for A
      site function and, moreover, suggest a common mechanism of action for these
      miscoding agents, even though they appear to have distinctly different modes of
      interaction with 16 S rRNA. In contrast to the miscoding agents, we find that a
      streptomycin-dependence (SmD) mutation in protein S12, which causes ribosomes to
      be hyperaccurate, antagonizes tRNA-dependent protection of G530. The possibility
      that 5' or 3' flanking regions of mRNA could be involved in tRNA-dependent
      protection of G530 was tested by using different lengths of oligo(U) to promote
      binding of tRNA(Phe) to the A site. The relative levels of protection of G530,
      A1492 and A1493 were unchanged as the size of the mRNA fragment was decreased
      from 16 to 6 bases in length. We conclude, therefore, that for protection of G530
      to be the result of direct contact with message, it must necessarily be located
      directly at the decoding site; otherwise, its protection is best explained by
      allosteric interactions, either with mRNA, or with the codon-anticodon complex.
      These results are discussed in terms of a model wherein the conformation of the
      530 loop is correlated with the affinity of the ribosome for elongation factor
      Tu.

PMID- 8289239
TI  - Translational initiation on structured messengers. Another role for the Shine
      Dalgarno interaction.
AB  - Translational efficiency in Escherichia coli is in part determined by the Shine
      Dalgarno (SD) interaction, i.e. the base-pairing of the 3' end of 16S ribosomal
      RNA to a stretch of complementary nucleotides in the messenger, located just
      upstream of the initiation codon. Although a large number of mutations in SD
      sequences have been produced and analysed, it has so far not been possible to
      find a clear-cut quantitative relationship between the extent of the
      complementarity to the rRNA and translational efficiency. This is presumably due
      to a lack of information about the secondary structures of the messengers used,
      before and after mutagenesis. Such information is crucial, because intrastrand
      base-pairing of a ribosome binding site can have a profound influence on its
      translational efficiency. By site-directed mutagenesis, we have varied the extent
      of the SD complementarity in the coat-protein gene of bacteriophage MS2. The
      ribosome binding site of this gene is known to adopt a simple hairpin structure.
      Substitutions in the SD region were combined with other mutations, which altered
      the stability of the structure in a predictable way. We find that mutations
      reducing the SD complementarity by one or two nucleotides diminish translational
      efficiency only if ribosome binding is impaired by the structure of the
      messenger. In the absence of an inhibitory structure, these mutations have no
      effect. In other words, a strong SD interaction can compensate for a structured
      initiation region. This can be understood by considering translational initiation
      on a structured ribosome binding site as a competition between intramolecular
      base-pairing of the messenger and binding to a 30 S ribosomal subunit. A good SD
      complementarity provides the ribosome with an increased affinity for its binding
      site, and thereby enhances its ability to compete against the secondary
      structure. This function of the SD interaction closely parallels the RNA
      unfolding capacity of ribosomal protein S1. By comparing the expression data from
      mutant and wild-type SD sequences, we have estimated the relative contribution of
      the SD base-pairs to ribosome-mRNA affinity. Quantitatively, this contribution
      corresponds quite well with the theoretical base-pairing stabilities of the wild
      type and mutant SD interactions.

PMID- 8289240
TI  - The loop sequence plays crucial roles for isomerization of intramolecular DNA
      triplexes in supercoiled plasmids.
AB  - The effect of base composition in the central region of polypurine.polypyrimidine
      (Pur.Pyr) tracts on the formation of intramolecular DNA triplexes in plasmids was
      examined using chemical probes (diethyl pyrocarbonate and OsO4), and two
      dimensional (2-D) agarose gel electrophoresis. Two isomers exist for an
      intramolecular triplex: one with the 3'-half of the Pyr strand as the third
      strand (H-y3) and the other with the 5'-half of the Pyr strand as the third
      strand (H-y5). It was shown that the content and position of G + C residues in
      the triplex loop region (the center of Pur.Pyr tracts) are primary determinants
      for the isomerization between the H-y3 and H-y5 triplexes. Divalent metal ions
      such as Mg2+ and negative supercoiling also modulate the isomerization: the H-y5
      conformation is stabilized by the divalent metal ions and/or under relatively
      lower negative supercoiling. 2-D gel analyses revealed that two isomers, H-y3 and
      H-y5, are topologically non-equivalent: the H-y3 formation relaxes one more
      supercoil turn than H-y5. As the G + C content in the center of Pur.Pyr tracts
      increases, the triplex requires more supercoil energy for formation. Therefore,
      the base-pair opening in the center of Pur.Pyr tracts is the initial and critical
      step in the pathway for the formation of triplex as well as the isomerization.
      The role of the triplex loop sequence is explained by a model in which the
      nucleation process of H-y3 formation requires a wide range of base-pair opening
      compared to that of H-y5: such unwinding would not be favored for the central
      region of the duplex with high G + C content and so it would be in the presence
      of Mg2+, and thereby the H-y5 formation is promoted.

PMID- 8289241
TI  - Periodicity of dinucleotides in nucleosomes derived from simian virus 40
      chromatin.
AB  - It is thought that statistical analysis of dinucleotide periodicities can provide
      insight into the general features of nucleosome forming sequences. The chromatin
      of simian virus 40 (SV40) provides a model for a unique DNA sequence that is
      found in association with histones in vivo. I have therefore analyzed the
      periodicity of dinucleotides in a collection of cloned nucleosomal DNA fragments
      prepared from SV40 chromatin isolated under relatively mild conditions, in order
      to learn about the generality of results obtained from the statistical approach
      and to examine the SV40 data set in the context of models that have been proposed
      to explain the molecular basis of nucleosome formation. In one study, I assumed a
      symmetry in the distribution of dinucleotides with respect to the nucleosome dyad
      position and considered complementary dinucleotides to be equivalent, i.e. AA =
      TT and GG = CC. The results showed a periodic signal for GG/CC but not for AA/TT,
      purine-purine, and pyrimidine-pyrimidine dinucleotides. In a second study, the
      SV40 nucleosomal DNA fragments were aligned and examined with respect to the late
      strand of the viral genome to determine the distribution of dinucleotides in one
      direction. Fourier analysis revealed periodic signals for AA/TT (10.26 bp) and
      GG/CC (10.0 bp) and indicated that AA dominates the occurrences of AA/TT and GG
      dominates the occurrences of GG/CC. The results of both studies implied that
      there might be an asymmetry and a directionality in the distribution of certain
      dinucleotides in nucleosomes.

PMID- 8289242
TI  - The Bacillus subtilis spoVD gene encodes a mother-cell-specific penicillin
      binding protein required for spore morphogenesis.
AB  - The Bacillus subtilis spoVD gene has been cloned and sequenced. It encodes a
      71,262 Da protein with extensive sequence similarity to penicillin-binding
      proteins from various organisms. The context of this gene in the B. subtilis
      chromosome, immediately upstream of the mur operon, suggests that it is related
      to the pbpB gene of Escherichia coli, which is involved in the synthesis of
      septal peptidoglycan during cell division. Expression of spoVD in E. coli leads
      to the synthesis of a membrane-associated protein of the size expected for SpoVD,
      which can bind labelled penicillin. However, insertional disruption of the spoVD
      gene has no effect on vegetative growth or division: a second pbp-like gene
      immediately upstream of spoVD is probably the functional homologue of E. coli
      pbpB. spoVD seems instead to have a specialized role in the morphogenesis of the
      spore cortex, which is a modified form of peptidoglycan. spoVD transcription
      appears to occur from a promoter recognized by the sigma E form of RNA
      polymerase. Analysis of the expression of a spoVD'-lacZ reporter gene supports
      this notion and indicates that a second level of negative regulation is dependent
      on the SpoIIID protein. SpoVD synthesis probably occurs only in the mother cell
      since both sigma E and SpoIIID are thought to be specific to this cell type. Such
      localization of SpoVD synthesis was supported by the results of a genetic test
      showing that expression of spoVD only in the mother cell is sufficient for spore
      formation. The results support the proposition that spore cortex formation is
      determined primarily by the mother cell.

PMID- 8289243
TI  - Explanation for different types of regulation of arginine biosynthesis in
      Escherichia coli B and Escherichia coli K12 caused by a difference between their
      arginine repressors.
AB  - In Escherichia coli K12, formation of the enzymes of arginine biosynthesis are
      controlled by arginine, with complete repression during growth with added
      arginine, severe repression (about 95%) during growth without added arginine and
      complete derepression during arginine-limited growth. In E. coli B, the degree of
      repression is not correlated with arginine concentrations. Under all conditions
      of growth enzyme formation is repressed, with repression being somewhat less in a
      medium with arginine than in a medium without arginine. These differences in
      repressibility between the two strains have been shown previously to be due to
      the presence of different alleles of argR, the gene for the arginine repressor.
      Here we have compared the binding of the two repressors to the operator sites of
      argF (ARG boxes). In DNase I footprinting and gel retardation experiments with
      argF ARG boxes we have shown that the arginine repressor of E. coli K12 bound to
      arginine (ArgRK-arg) has a greater affinity than the arginine repressor of E.
      coli B bound to arginine (ArgRB-arg), whereas free ArgRB (ArgRBf) has a much
      stronger affinity than free ArgRK (ArgRKf). The stronger binding of ArgRBf can
      explain the repression seen in E. coli B during arginine-limited growth and
      indicates that ArgRBf, but not ArgRKf, is able to repress enzyme synthesis under
      physiological conditions. The weaker repression of E. coli B than of E. coli K12
      seen in the presence of arginine can be explained by the lower affinity of ArgRB
      arg for operator sites as compared to ArgRK-arg. Another contributing cause for
      the weaker repression is the reduction of ArgRBf concentration due to
      autoregulation of the gene for the repressor. Thus the combined effects of
      repression by ArgRBf, but not ArgRKf, with the weaker repression by ArgRB-arg as
      compared to ArgRK-arg, convert the arginine dependent regulation in E. coli K12
      to arginine independent regulation in E. coli B.

PMID- 8289244
TI  - Increased longevity of EF-1 alpha high-fidelity mutants in Podospora anserina.
AB  - Various translation initiation and elongation factors seem to participate in the
      control of the cellular proliferation and the ageing process in higher
      eukaryotes. Studies indicate that EF-1 alpha, one of the translation elongation
      factors, may be one of the major components involved. We here present the cloning
      of the filamentous fungus P. anserina EF-1 alpha encoding gene and show that
      strains bearing high fidelity mutations in the EF-1 alpha gene have a drastically
      increased longevity as well as an impairment in sporulation. This suggests that
      EF-1 alpha involved in the sexual and senescence processes in lower eukaryotes,
      through the control of translational errors.

PMID- 8289245
TI  - Characterization of an in vitro-selected RNA ligand to the HIV-1 Rev protein.
AB  - A small RNA ligand with high affinity for the HIV-1 Rev protein, generated by the
      SELEX in vitro evolution method, was used in a series of chemical modification
      studies to aid in determining the secondary structure of the ligand, to detect
      which modifications interfere with the binding of the ligand to Rev, and to find
      those modifiable groups that are protected from attack when bound to the Rev
      protein. This SELEX RNA ligand, like the high-affinity binding site of the Rev
      responsive element, seems to bind the Rev protein within or along the major
      groove. There are two major regions of the RNA that interact with the Rev
      protein, and these regions appear to be close in space. Additionally, this high
      affinity ligand has been used as the basis for an additional "biased
      randomization" SELEX procedure, in an effort to gain comprehensive information on
      the RNA sequences and structural elements necessary for efficient binding to the
      Rev protein. This complementary experimental approach supports the structural
      conclusions of our chemical modification data.

PMID- 8289246
TI  - Analysis of functional domains of the packaging proteins of bacteriophage T3 by
      site-directed mutagenesis.
AB  - Intracellular phage T3 DNA is synthesized as a concatemer in which unit-length
      molecules are jointed together in head-to-tail fashion through terminally
      redundant sequences. The concatemeric DNA is processed and packaged into the
      prohead with the aid of non-capsid proteins, gp18 and gp19. We have developed a
      defined system, composed of purified gp18, gp19 and proheads, and a crude system,
      composed of lysates of T3 infected cells, for in vitro packaging of T3 DNA. The
      defined system displays an ATPase activity which is composed of DNA packaging
      dependent and -independent ATPases (pac- and nonpac-ATPases, respectively). In
      the crude system, DNA is packaged by a way of concatemer as an intermediate. gp19
      has ATP binding activity and three ATP binding and two Mg2+ binding consensus
      motifs in its amino acid sequence. We have expanded the previous studies on the
      roles of these domains in the DNA packaging reaction by more extensive analysis
      by site-directed mutagenesis. gp19 mutants, including the previously isolated
      four mutants, were divided into four groups according to the DNA packaging
      activity in the defined and crude systems: group 1 mutants were defective in both
      systems (gp19-G61D, which is a gp19 mutant with Gly to Asp at amino acid 61 and
      so on, and gp19-H344D); the group 2 mutant had decreased activity in both systems
      (gp19-G429R); group 3 mutants were active in the defined system but defective in
      the crude system (gp19-G63D, gp19-H347R, gp19-G367D, gp19-G369D, gp19-G424E);
      group 4 mutants had almost the same activity as gp19-wt (gp19-K64T, gp19-K370I,
      gp19-G429L, gp19-K430T and gp19-H553L). Group 1 mutants had an altered
      conformation, resulting in defective interaction with ATP and in abortive binding
      to the prohead, and lost specifically the pac-ATPase activity. The group 2 mutant
      had an increased pac-ATPase activity in spite of the decreased DNA packaging
      activity, indicating that this mutant is inefficient in coupling of ATP
      hydrolysis to DNA translocation. The inability of the group 3 mutants except gp19
      H347R to package DNA in the crude system would be due to a defect in processing
      of concatemer DNA. gp19-H347R would be a mutant defective in the initiation
      event(s) of DNA packaging.

PMID- 8289247
TI  - Molecular models and structural comparisons of native and mutant class I
      filamentous bacteriophages Ff (fd, f1, M13), If1 and IKe.
AB  - The filamentous bacteriophages are flexible rods about 1 to 2 microns long and 6
      nm in diameter, with a helical shell of protein subunits surrounding a DNA core.
      The approximately 50-residue coat protein subunit is largely alpha-helix and the
      axis of the alpha-helix makes a small angle with the axis of the virion. The
      protein shell can be considered in three sections: the outer surface, occupied by
      the N-terminal region of the subunit, rich in acidic residues that interact with
      the surrounding solvent and give the virion a low isoelectric point; the interior
      of the shell, including a 19-residue stretch of apolar side-chains, where protein
      subunits interact mainly with each other; and the inner surface, occupied by the
      C-terminal region of the subunit, rich in basic residues that interact with the
      DNA core. The fact that virtually all protein side-chain interactions are between
      different subunits in the coat protein array, rather than within subunits, makes
      this a useful model system for studies of interactions between alpha-helix
      subunits in a macromolecular assembly. We describe molecular models of the class
      I filamentous bacteriophages. This class includes strains fd, f1, M13 (these 3
      very similar strains are members of the Ff group), If1 and IKe. Our model of fd
      has been refined to fit quantitative X-ray fibre diffraction data to 30 A
      resolution in the meridional direction and 7 A resolution in the equatorial
      direction. A simulated 3.3 A resolution diffraction pattern from this model has
      the same general distribution of intensity as the experimental diffraction
      pattern. The observed diffraction data at 7 A resolution are fitted much better
      by the calculated diffraction pattern of our molecular model than by that of a
      model in which the alpha-helix subunit is represented by a rod of uniform
      density. The fact that our fd model explains the fd diffraction data is only part
      of our structure analysis. The atomic details of the model are supported by non
      diffraction data, in part previously published and in part newly reported here.
      These data include information about permitted or forbidden side-chain
      replacements, about the effect of chemical modification, and about spectroscopic
      experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8289248
TI  - Evidence for strained interactions between side-chains and the polypeptide
      backbone.
AB  - In most proteins, a small but significant fraction of residues adopt phi,psi
      angles that generate unfavorable steric interactions between side-chain atoms and
      the peptide backbone. For the small protein staphylococcal nuclease, the X-ray
      structure reveals that 18 of 133 residues occupy unusual and, presumably,
      energetically unfavorable backbone conformations. To quantify the amount of
      strain energy generated by these local interactions, we have analyzed the changes
      in stability that accompany replacement of the wild-type side-chain with glycine,
      a residue that can access a much larger set of phi,psi angles without energy
      penalty. To correct for the many other sources of stability loss that might
      accompany this mutation, the glycine mutant was compared to an alanine mutant at
      the same position and the resulting free energy difference delta delta GG-->A was
      then compared to the average delta delta GG-->A at all other, unstrained
      positions in the nuclease occupied by similar amino acid types. In addition,
      potential steric clashes were introduced by substituting alanine at each of six
      positions occupied in the wild-type by glycine with phi,psi angles that are
      unfavorable for all other residue types. The data suggest that residues with
      phi,psi angles outside the preferred alpha-helical and beta-sheet regions
      represent sites of local strain energy that lower the stability of the native
      state by 1 to 2 kcal/mol and, in some cases, as much as 3 to 4 kcal/mol. Given
      that 10 to 20% of residues in globular proteins adopt phi,psi angles outside the
      preferred alpha-helical and beta-sheet regions, this implies that there is on the
      order of 20 kcal/mol of strain energy in a protein of 100 residues that may be
      relieved by appropriate mutations.

PMID- 8289249
TI  - Conformational behaviour of the active and inactive forms of the nucleocapsid
      NCp7 of HIV-1 studied by 1H NMR.
AB  - The nucleocapsid protein NCp7 of the human immunodeficiency virus type I (HIV-1)
      is a 72 amino acid peptide containing two zinc fingers of the type CX2CX4HX4C
      linked by a short basic sequence 29RAPRKKG35. NCp7 was shown to activate in vitro
      both viral RNA dimerization and replication primer tRNA(Lys,3) annealing to the
      initiation site of reverse transcription. In order to clarify the possible
      structural role of the zinc fingers in the various functions of NCp7, complete
      sequence specific 1H NMR assignment of the entire protein was achieved by two
      dimensional NMR experiments. Moreover, to characterize the role of the peptide
      linker in NCp7 folding, a synthetic analogue with an inversion of Pro31
      configuration was studied by NMR and fluorescence techniques. Several long range
      NOEs implying amino acid protons from the folded zinc fingers and the spacer,
      such as Ala25 and Trp37, Phe16 and Trp37, Arg32 and Trp37, Lys33 and Trp37, Cys18
      and Lys33 disappeared in the D-Pro31 (12-53)NCp7, confirming the spatial
      proximity of the two CCHC boxes observed in the (13-51)NCp7. This was also
      confirmed by iodide fluorescence quenching experiments. The N and C-terminal
      parts of NCp7 displayed a large flexibility except for two short sequences Tyr56
      to Gly58 and Tyr64 to Gly66, which seemed to oscillate between random-coil and
      helical conformations. The biological relevance of the structural characteristics
      of NCp7 was studied in vitro and in vivo. Substitution of Pro31 by D-Pro31 in the
      active (13-64)NCp7 peptide led to a severe reduction of dimerization in vitro.
      Moreover, site-directed mutagenesis substituting Leu for Pro31 resulted in the
      formation of non-infectious and immature viral particles. These results suggest
      that the spatial proximity of the zinc fingers induced by the peptide linker,
      plays a critical role in encapsidation of genomic RNA and morphogenesis of HIV-1
      infectious particles.

PMID- 8289250
TI  - Thermal expansion of hen egg-white lysozyme. Comparison of the 1.9 A resolution
      structures of the tetragonal form of the enzyme at 100 K and 298 K.
AB  - The average structural and dynamic properties of tetragonal hen egg-white
      lysozyme have been compared, in structures refined at 1.9 A resolution, using
      data collected at 100 K and 298 K. The molecule expands by 1.8% over this
      temperature range with the expansion occurring primarily in its small sub-atomic
      sized spaces in an anisotropic manner. Hen egg-white lysozyme consists of two
      domains: domain 1 (residues 40 to 88) is composed primarily of beta-sheet and is
      observed to expand by only 0.3%; domain 2 (residues 1 to 39 and 89 to 129) is
      chiefly alpha-helix and is observed to expand by 2.2%. This is consistent with
      previous observations that proteins composed primarily of alpha-helix expand more
      with temperature than do those composed primarily of beta-sheet. The largest
      movement in the molecule is undergone by the two domains of the structure that
      move further apart as the temperature is raised. This motion is not a cleft
      opening but rather consists of a tilt by 2.3 degrees of domain 1 away from domain
      2. Within the individual domains the largest movement is undergone by loop T1 of
      domain 2, consisting of residues 17 to 23. This loop moves in the opposite
      direction to the rest of the molecule as the temperature is raised. Average
      temperature factors for the room-temperature and low-temperature structures are
      15.2 A2 and 8.1 A2, respectively, when all protein atoms are considered, while
      these values are 14.0 A2 and 7.8 A2, when only main-chain atoms (N, C alpha, C)
      are taken into account. An examination of the main-chain averaged B-factor per
      residue shows that residues involved in intermolecular protein-protein contacts,
      with symmetry-related molecules, have somewhat lower B-factors than the average
      and undergo smaller than average changes in B-factor as the temperature is
      lowered.

PMID- 8289251
TI  - MONTY: a Monte Carlo approach to protein-DNA recognition.
AB  - A Monte Carlo method is described for automated docking of proteins on DNA. The
      simulation program MONTY keeps the entire DNA and the protein backbone and core
      fixed while protein surface side-chains are allowed to rotate freely. The entire
      protein is rotated and translated by small random steps in order to find the best
      fit with the DNA. New configurations are accepted on basis of their Boltzmann
      probability. Protein-DNA interaction is represented by square well potentials for
      hydrogen bond and van der Waals interactions. The structure with the largest
      interaction energy encountered during the simulation is saved. The method is
      tested on complexes of the 434 Cro protein and its operator DNA where the protein
      is shifted up or down one or two base-pairs and is subsequently allowed to find
      back its native binding site. This protocol is performed for shifted complexes
      derived from the crystal structure, shifted complexes where the crystal structure
      DNA is replaced by standard B-DNA and shifted complexes where in addition the
      protein is replaced by protein from the uncomplexed crystal structure. In all
      three cases the six lowest energy structures correspond to complexes close to the
      native complex. The quality of sequence specific recognition diminishes, however,
      when the molecular surface complementarity between protein and DNA decreases.

PMID- 8289252
TI  - Sequence dependence of DNA structure in solution.
AB  - Sequence-dependent structural variations in DNA can influence its binding by
      ligands and proteins. However, relatively little is known about sequence
      structure relationship for arbitrary DNA sequences. The 1H two-dimensional NOESY
      data presented here for ten oligonucleotide duplexes show pronounced sequence
      dependent changes in at least two types of internucleotide distances commonly
      used in sequential connectivity assignments, namely the H-6/H-8 to preceding (5')
      H-1' distance (S1) and the H-6/H-8 to preceding (5') H-2'' distance (S2). On the
      basis of these two measured distances, all dinucleotide steps can be divided into
      four different groups: Y-R, R-Y, R-R and Y-Y, where R is purine and Y is
      pyrimidine. These data suggest some rules for the variation in these distances
      along DNA duplexes. Correlations between these distances and helical parameters
      of DNA are discussed in comparison to well-resolved X-ray structures of B-type
      DNA.

PMID- 8289253
TI  - Oxygen radical induced mutagenesis is DNA polymerase specific.
AB  - Oxygen free radicals are produced in large amounts by normal cellular processes.
      Damage to DNA by these reactive species has been implicated in mutagenesis and
      may be important in the etiology of a variety of human diseases. In this study we
      investigate the types of mutations produced in vitro as a result of DNA damage by
      oxygen free radicals. We used a lacZ alpha forward mutation assay in which M13
      viral DNA is damaged in vitro, replicated with purified DNA polymerase alpha or
      beta, transfected into E. coli, and screened for mutations by reduced alpha
      complementation of beta-galactosidase activity. By determining the effects of
      damaged templates on the fidelity of individual DNA polymerases involved in
      replication and repair, we address the role of specific DNA polymerases in
      mutagenesis induced by reactive oxygen species. Aerobic incubation of DNA with
      100 microM CuCl, 10 microM H2O2 and 100 microM ascorbic acid results in a 3.3
      fold and a 3.6-fold elevation in mutation frequency for polymerases alpha and
      beta, respectively. The specificity and location of the induced mutations,
      however, are entirely different. For polymerase alpha, A to C, and C to A
      transversions and deletions of C are each elevated more than 10-fold over their
      frequencies on undamaged template. For polymerase beta, A to T, C to T, C to A, G
      to C, and G to T substitutions, and deletions of G are elevated by damage. The
      frequency of mutants containing two or more closely spaced substitutions is also
      markedly increased by template damage although the types of mutations and their
      positions are again specific to each DNA polymerase. We conclude that, for
      oxidative lesions, the frequency and the types of mutations are determined in
      part by the DNA polymerase that encounters the site of damage.

PMID- 8289254
TI  - Crystal structure of the fungal peroxidase from Arthromyces ramosus at 1.9 A
      resolution. Structural comparisons with the lignin and cytochrome c peroxidases.
AB  - The crystal structure of the peroxidase (donor: H2O2 oxidoreductase, EC 1.11.1.7)
      from the hyphomycete Arthromyces ramosus (ARP) has been determined by the
      multiple isomorphous replacement method and refined by the simulated annealing
      method to a crystallographic R-factor of 17.4% for the 19,191 reflections with F
      > 2 sigma F between 7.0 and 1.9 A resolution. The model includes residues 9 to
      344, the heme group, two N-acetylglucosamine residues, two calcium ions and 246
      water molecules. The root-mean-square deviation of bond lengths from the ideal
      values is 0.02 A. The mean coordinate error is estimated as 0.2 A. The electron
      density of the glycine-rich region of the amino-terminal eight residues was
      invisible. ARP has ten major and two short alpha-helices and a few short beta
      strands. The overall tertiary structure of ARP is similar to that of yeast
      cytochrome c peroxidase (CCP) and is particularly similar to that of the lignin
      peroxidase (LiP) from Phanerochaete chrysosporium. Relative to CCP, ARP and LiP
      each have an extension of approximately 40 residues at the carboxy terminus. All
      eight cysteine residues in ARP form disulfide bonds (C12:C24, C23:C293, C43:C129
      and C257:C322). Two calcium sites are inaccessible to solvent. The four disulfide
      bonds and two calcium sites, which are lacking in CCP, are conserved in ARP and
      LiP. The bond from Asn304C to Ala305N in ARP is the site sensitive to proteases.
      An Asx turn present in the Asn303 to Ala305 segment appears to orient the side
      chain of Asn304 to outward from the molecule, rendering it easily trappable by
      pockets of proteases. The proximal heme ligand is His184 in helix F (distance of
      N epsilon 2 ... Fe, 2.10 A), and one of several water molecules in the distal
      pocket of the heme bridges the iron atom and the N epsilon 2 of His56. The
      orientation of the imidazole ring of the distal histidine residue relative to the
      heme group in ARP differs significantly from that in LiP. The access channel to
      the distal side of the heme of ARP is markedly wider along the heme plane than
      that of LiP. Many of the amino acid residues that comprise the entrance of this
      channel differ for ARP and LiP. This may account for the differences in substrate
      specificity.

PMID- 8289255
TI  - Ligand docking to proteins with discrete side-chain flexibility.
AB  - An algorithm is described that explores the conformational degrees of freedom of
      the amino acid side-chains and of the ligand when docking a putative ligand into
      a receptor site. For a given orientation of the ligand relative to the protein,
      the method can find the lowest energy combination of amino acid side-chains and
      ligand conformations as well as all other combinations in order of increasing
      energy within a specified energy cutoff. The amino acid side-chains and the
      ligand are restricted to discrete low-energy conformations, determined for the
      former by analysing high-resolution protein structures and in the latter case
      from a conformational analysis. Coupled to an algorithm for exploring the six
      degrees of orientational freedom of the ligand with respect to the receptor, the
      method can be used to perform conformationally flexible ligand docking. A
      combination of two search methods is employed to explore the conformational
      degrees of freedom: Dead End Elimination and the A* algorithm. When no ligand is
      present the approach can be used to predict the lowest energy combinations of
      side-chain conformations for a given protein backbone structure. The approach is
      employed to illustrate how such a procedure can be used to estimate the
      conformational entropy change that accompanies the formation of an intermolecular
      complex between a protein and a ligand and to demonstrate that the protein's
      conformational entropy may in some cases increase on binding the ligand. This is
      due to a modification of the protein's energy hypersurface that makes more
      conformational states accessible. Our results highlight the need for appropriate
      methods to estimate the strength of binding.

PMID- 8289256
TI  - Crystallization of canine cardiac calsequestrin.
AB  - Calsequestrin is the major Ca2+ binding protein in the lumen of the sarcoplasmic
      reticulum membranes. Two X-ray quality crystal forms of canine cardiac
      calsequestrin were obtained by the hanging drop method using KCl as a
      precipitant. One form is monoclinic (space group P2(1), a = 73.4 A, b = 104.4 A,
      c = 60.2 A, beta = 120.4 degrees) with two molecules in the asymmetric unit and a
      solvent content of approximately 40%. The second form is trigonal (P3(1)21 or
      P3(2)21, a = b = 99.3 A, c = 89.8 A) with a single molecule in the asymmetric
      unit and 55% solvent content. Cross rotation function calculations show that
      despite the different space groups the packing of the molecules in both crystals
      is likely to be similar suggesting the existence of a stable dimer. The
      monoclinic crystals diffract beyond 3 A using a laboratory rotating anode source,
      while under the same conditions the trigonal crystals diffract only to
      approximately 4.5 A. This is the first report of successful preparation of X-ray
      quality crystals of a high capacity Ca2+ binding protein.

PMID- 8289257
TI  - Crystallographic characterization and molecular symmetry of edestin, a legumin
      from hemp.
AB  - Edestin, a legumin class reserve protein from hemp seeds having six identical
      subunits was crystallized from ammonium phosphate at pH 5 and subsequently
      characterized by X-ray diffraction. The crystals are of space group R32 with a =
      127 A and gamma = 116 degrees having an equivalent triply centered hexagonal cell
      of a = b = 215 A, c = 80 A. There is one hexameric protein in the rhombohedral
      unit cell, hence the subunits of the Edestin molecule must be arranged with 32
      point group symmetry.

PMID- 8289258
TI  - Crystallization and preliminary X-ray diffraction studies on a
      trypsin/chymotrypsin double-headed inhibitor from horse gram.
AB  - The Bowman-Birk family of proteinase inhibitors from seeds of leguminous plants
      usually have a molecular mass of 8000 to 10,000 Da. Horse gram (Dolichos bifloros
      or Macrotyloma uniflorum) seeds contain an unusual Bowman-Birk inhibitor of
      molecular mass 15,500 Da active against both trypsin and chymotrypsin. In order
      to elucidate its three-dimensional structure, its evolutionary relationship with
      the more usual Bowman-Birk inhibitors and to study the structure-function
      properties, this inhibitor has been purified and crystallized. The purified
      protein crystallizes easily under a variety of conditions in different crystal
      forms. Crystals obtained by precipitating the protein (3 to 5 mg/ml in 50mM
      Tris.HCl (pH 8.0)) with 5% ammonium sulphate and 2 to 3% PEG 4000 appear to be
      suitable for structure determination by X-ray diffraction. The crystals belong to
      cubic space group P2(1)3 (a = 110.81 A) and diffract X-rays to beyond 3.0 A
      resolution.

PMID- 8289259
TI  - Crystallization of D-lactate dehydrogenase from Lactobacillus bulgaricus.
AB  - The D-lactate dehydrogenase (D-LDH) from Lactobacillus bulgaricus has been
      purified and co-crystallized with its cofactor NAD+. Crystals suitable for X-ray
      diffraction experiments have been obtained from an ammonium sulfate solution by
      the hanging-drop method. The crystals belong to the orthorhombic space group C222
      (or C222(1)) with cell dimensions a = 76.5 A, b = 93.3 A, c = 118.4 A and one
      monomer of 37,000 daltons per asymmetric unit. They diffract beyond 3.0 A
      resolution. Sequence comparison suggests that D-LDHs have no evolutionary
      relationship to L-LDHs and belong instead to the family of the D-2-hydroxyacid
      dehydrogenases. The X-ray crystallographic structure of the D-LDH from
      Lactobacillus bulgaricus will be a decisive test of this hypothesis.

PMID- 8289260
TI  - Crystallization and preliminary X-ray analysis of the monoclonal anti-tumor
      antibody BR96 and its complex with the Lewis Y determinant.
AB  - The monoclonal anti-tumor antibody BR96 binds a tetrasaccharide, Lewis y (Le(y)),
      in vitro and recognizes a Le(y)-bearing or Le(y)-related tumor-associated antigen
      in vivo. The Fab of the murine monoclonal antibody, mBR96 (IgG3, kappa), and the
      Fab' of its human chimera, cBR96 (IgG1, kappa), and their complexes with Le(y)
      have been screened for crystallization conditions. Crystals suitable for X-ray
      diffraction have been obtained for uncomplexed cBR96 Fab', cBR96 Fab' in complex
      with Le(y) and mBR96 Fab in complex with Le(y). The symmetry of the cBR96 Fab'
      crystals is consistent with space group P2(1)2(1)2, a = 61.1 A; b = 174.3 A; c =
      45.6 A; the symmetry of the cBR96 Fab'-Le(y) complex crystals with space group
      P4(3)2(1)2 (or its enantiomorph), a = b = 82.2 A; c = 167.1 A and the symmetry of
      the mBR96 Fab-Le(y) complex crystals with space group P2(1)2(1)2(1), a = 69.4 A;
      b = 84.9 A; c = 86.8 A.

PMID- 8289261
TI  - A beta-tubulin gene of Naegleria encodes a carboxy-terminal tyrosine. Aromatic
      amino acids are conserved at carboxy termini.
AB  - A gene that directs the programmed synthesis of flagellar beta-tubulin during the
      rapid differentiation of Naegleria gruberi from amoebae to flagellates has been
      cloned and sequenced. The intronless gene is one of 8 to 10 similar but non
      identical genes that are dispersed in the genome. beta-Tubulin mRNA homologous to
      this gene family is expressed transiently during differentiation, and has not
      been detected in amoebae. The encoded beta-tubulin is strongly conserved, with
      features that closely resemble the beta-tubulins of diverse organisms, especially
      organisms that, like Naegleria, use tubulin to assemble flagellar axonemes. In
      most sequenced alpha-tubulins, the encoded carboxy-terminal amino acid is
      tyrosine, which undergoes post-translational removal and readdition, conserved
      processes of unknown function. In N. gruberi, unusually, the terminus of alpha
      tubulin is encoded as glutamine while that of beta-tubulin is tyrosine. The
      presence of these divergent termini on subunits of a conserved tubulin provoked
      us to re-examine aromatic amino acids at the termini of alpha- and beta-tubulins.
      Although evolution has tinkered extensively with the carboxy-terminal domains of
      tubulin subunits, we find an unexpected conservation. In every organism or cell
      type for which both tubulin subunits have been sequenced, except the ciliate
      Stylonychia lemnae, at least one tubulin subunit of some or all tubulin
      heterodimers terminates in an aromatic amino acid, either tyrosine or
      phenylalanine. This remarkable conservation of carboxy-terminal aromatic amino
      acids suggests that these residues serve some crucial function.

PMID- 8289262
TI  - Evidence that GHN phase bias does not constitute a framing code.
AB  - It has been suggested that a triplet repeated pattern found in coding sequences,
      the G-nonG-N or GHN phase bias, serves a framing function during protein
      synthesis. To test this idea, the framing characteristics of a highly GHN biased
      sequence are examined. No effects on reading frame maintenance are observed
      despite the use of sensitive frameshift assays. Specifically, first the GHN phase
      is not more accurate than the alternative overlapping phases (i.e., HNG and NGH).
      Second, ribosomes do not exhibit any significant tendency to slip from the
      alternative frames into the GHN pahse. In addition, examination of Escherichia
      coli programmed frameshift sites does not support roles for GHN phase bias in
      programmed frameshifting. Framing functions for GHN phase bias, if they occur at
      all, must be extremely limited.

PMID- 8289263
TI  - SAV, an archaebacterial gene with extensive homology to a family of highly
      conserved eukaryotic ATPases.
AB  - Nucleotide sequencing of a region of the hyperthermophilic archaebacterium
      Sulfolobus acidocaldarius allowed us to identify an open reading frame of 780
      amino acids strikingly similar to a family of eukaryotic ATPases, involved in a
      variety of biological functions. Sequence analysis of the predicted polypeptide
      revealed 63 to 66% similarity with S. cerevisiae CDC 48p and its related genes in
      amphibians (p97ATPase) and mammals (Valosin Containing Protein, VCP), all
      possibly involved in the regulation of the cell cycle. The finding of an
      archaebacterial equivalent of these proteins with a high degree of similarity
      suggests that it represents the same gene in these various species. The new
      archaebacterial ORF, called SAV (S. acidocaldarius VCP-like) exhibited the usual
      signature of all members of the family, a highly conserved domain of about 200
      amino acids, which is duplicated. Thus, apart from the VCP-like proteins, SAV
      also appeared similar, although less clearly, to other ATPases, members of the
      family, involved in vesicle-mediated transport (NSF, Sec18p), peroxysome assembly
      (PAS1p), and gene expression in yeast (SUG1p) and in human immunodeficiency virus
      (TBP-1). Finally, the discovery of the archaebacterial gene could enlighten not
      only the evolutionary relationships between the members of this complex ATPase
      family, but also the cellular function of these proteins, that is presently
      obscure.

PMID- 8289264
TI  - Crystal structure of apo-avidin from hen egg-white.
AB  - The three-dimensional structure of hen egg-white apo-avidin, crystallized in a
      tetragonal crystal form, has been refined to a crystallographic R-factor of 0.164
      (for the 6390 observed reflections in the 10.0 to 2.8 A resolution range). As in
      the case of holo-avidin, from which starting atomic co-ordinates were derived,
      the functional tetramer shows 2-pseudo 22 molecular symmetry. Each promoter is
      organized in an eight-stranded antiparallel orthogonal beta-barrel, with extended
      loop regions, which define the biotin binding pocket in the protomer core. In the
      absence of biotin the binding site is only partly occupied by water molecules.
      The structure of the binding site residues, as observed in apo-avidin, is highly
      complementary to that of the incoming biotin molecule, accounting for prompt and
      specific recognition. A crystal lattice contact may play a role in stabilizing
      the conformation of one protein loop, part of the biotin-binding pocket.

PMID- 8289265
TI  - Idiotope determining regions of a mouse monoclonal antibody and its humanized
      versions. Identification of framework residues that affect idiotype expression.
AB  - The contribution of framework regions (FRs) of antibody-variable domains to
      idiotype expression was studied by examining the interaction of various
      "humanized" versions of a mouse anti-TNF alpha monoclonal antibody (mAb78) with
      polyclonal and two monoclonal antibodies (mAb1G3 and mAb9F1), generated against
      the mAb78 idiotype. Humanized mAb78, bearing human constant domains and mouse
      complementarity-determining regions (CDRs) inserted with human FRs, was found to
      be five to sevenfold less reactive than mAb78 with polyclonal anti-idiotype
      antibodies and 200 to 300-fold less active in neutralizing TNF alpha. The
      substitution of heavy-chain FRs residues of the humanized antibody with original
      mouse residues 28 to 30, 48 to 49, 67 to 68, 70 to 71, 78, 80 and 82
      progressively restored the immunoreactivity with polyclonal immunoglobulin Gs to
      the level of a version having mouse heavy chain and human light chain FRs, and
      increased 10 to 20-fold the TNF alpha neutralizing activity. This suggests that
      at least some of these residues are critical for TNF alpha binding as well as for
      the expression of idiotopes that are strongly immunogenic in syngeneic animals.
      All antibody versions with either human or mouse FRs were able to bind to various
      extents mAb1G3, a gamma-type anti-Id antibody that inhibits mAb78/TNF alpha
      interaction by paratope blockade. At variance, only the antibody versions
      containing mouse FRs were able to bind mAb9F1, an alpha-type anti-Id antibody
      unable to block the access of TNF alpha to mAb78 paratopes. Substitution of heavy
      chain FR residues 28 to 30 markedly decreased the binding of mAb1G3 (100 to 1000
      fold). This suggests that these antibodies recognize CDR and FR idiotopes,
      respectively, that can be drastically modified by changes in the FRs. In
      conclusion, the results suggest that CDRs as well as FRs markedly contribute to
      antibody Id expression. Although strongly immunogenic idiotopes are probably
      located within the CDRs, the results also suggest that some FR residues are
      critically involved in shaping antibody Id diversity by affecting the structure
      of CDR-related idiotopes.

PMID- 8289266
TI  - Native collagen fibrils from echinoderms are molecularly bipolar.
AB  - Collagen fibrils are generally assumed to be cylinders with uniform diameters
      (except possibly at their ends) and to be composed of molecules all of which have
      the same polarity. These assumptions have been largely untested because of the
      extreme difficulty associated with isolating entire native fibrils. Intact
      collagen fibrils are readily extracted from certain echinoderms, however, and we
      have therefore analyzed the molecular structure of these fibrils. Our electron
      microscopic analyses show the above assumptions to be false: echinoderm fibrils,
      which previously have been shown to be symmetrically spindle shaped, are also
      molecularly bipolar. Their constituent molecules have their N-termini oriented
      toward the nearest fibril end, and they are antiparallel in the fibril center.
      The shape and molecular arrangement of these fibrils have implications for
      fibrillogenesis.

PMID- 8289267
TI  - Vertebrate (chick) collagen fibrils formed in vivo can exhibit a reversal in
      molecular polarity.
AB  - A reversal in molecular polarity can occur in vertebrate collagen fibrils. This
      has been demonstrated using a method for isolating, from chick embryo tendon,
      entire collagen fibrils 2 to 14 microns in length and suitable for electron
      optical examination. A polarity reversal is present in some, but not all, of
      these fibrils. Such fibrils have two N-ends. The transition region, occupying
      several D-periods in which the reversal occurs, is not restricted to a central
      location in a fibril. Analysis of the fibril banding pattern through the
      transition region shows that the relative axial alignment of antiparallel
      molecules brings oppositely-directed C-telopeptides into axial register. This
      could allow antiparallel molecules to be covalently linked via polymeric cross
      links involving these C-telopeptides.

PMID- 8289268
TI  - Domain interactions and connecting peptides in lens crystallins.
AB  - beta B2- and gamma B-crystallin from bovine eye-lens are closely related
      proteins, topologically distinct mainly by virtue of the linker peptide
      connecting the two domains in each polypeptide chain. In homodimeric beta B2
      crystallin, the extended conformation of the connecting peptide has been
      suggested to force the beta B2-molecule to favor intermolecular domain
      interactions compared with intramolecular contacts in monomeric gamma B
      crystallin. From this one may postulate that the conserved interdomain contacts
      are essential for the overall stability of crystallins. This was clearly
      confirmed for gamma B-crystallin, since its isolated C-terminal domain is
      significantly less stable than in the context of native gamma B. Exchanging the
      linker peptide of gamma B- for that of beta B2-crystallin yields a monomeric
      protein with stability characteristics identical to gamma B-crystallin. We
      conclude that the domain-interface itself rather than the connecting peptide
      determines the mode of domain association in crystallins, as the linker in the
      gamma B beta-mutant is evidently twisted to a turn similar to the one in natural
      gamma B-crystallin.

PMID- 8289269
TI  - Features in the 5' non-coding sequences of rabbit alpha and beta-globin mRNAs
      that affect translational efficiency.
AB  - The 5' non-coding sequence of rabbit beta-globin mRNA was mutagenized in an
      attempt to identify structural features that might contribute to the ability to
      support translation in an homologous rabbit reticulocyte lysate. Translational
      efficiency was not reduced by substitutions introduced in nearly every position
      of the beta-globin leader sequence, suggesting that the 5' non-coding domain of
      this highly efficient mRNA contains no special effector motifs. Instead,
      efficient translation appears to require only a moderately long leader sequence
      devoid of secondary structure, especially near the 5' end. Consistent with that
      interpretation, substitutions in several positions actually improved translation
      relative to the wild-type beta-globin leader sequence; experimental assessment of
      the secondary structure of these derivatives revealed a perfect inverse
      correlation between secondary structure content and translational efficiency.
      Other experiments probed the structural basis for the long-noted difference in
      translational efficiency between rabbit alpha and beta-globin mRNAs, a difference
      that was reproduced here using only the 5' non-coding domains of those mRNAs. The
      possibility that translation of ribosomal protein mRNAs might be modulated by a
      mechanism similar to that of alpha-globin mRNA is discussed. Because the beta
      globin leader sequence has been incorporated into some popular expression
      vectors, and because globin genes are targets for gene therapy, this analysis of
      how globin mRNA leader sequences function in translation and how they can be
      improved may have practical applications.

PMID- 8289270
TI  - Role of the sigma 70 subunit of Escherichia coli RNA polymerase in transcription
      activation.
AB  - The role of the sigma 70 subunit of Escherichia coli RNA polymerase in
      transcription activation by positive transcription factors was investigated. For
      this purpose, we constructed a nested set of E. coli rpoD deletion mutants
      generating carboxy-terminally truncated sigma 70 subunits of RNA polymerase in a
      high-expression plasmid. The purified mutant sigma 70 subunits were reconstituted
      into holoenzymes and examined in vitro for their promoter selectivity. As
      expected, since the -35 recognition helix of sigma 70 was deleted in all cases,
      the mutant enzymes were unable to initiate at factor-independent promoters,
      except for the special case of perfect "extended minus 10" promoters, at which
      the need for -35 sequence recognition by RNA polymerase is replaced by
      recognition of additional base-pairs in the -10 region. However, two factor
      dependent promoters, PhoB-dependent PpstS and cAMP receptor protein (CRP)
      dependent P1gal, could be activated for transcription by different subsets of the
      mutant holoenzymes, although these promoters do not contain the perfect extended 
      10 sequences. These results establish that -35 DNA recognition by sigma 70 is not
      essential for these cases. Presumably it is replaced by protein-protein contacts
      between RNA polymerase and the activator, which in both cases is bound to the DNA
      in a position overlapping the -35 region. Further, the detailed results support
      the view that the contact and/or activation sites for these two factors may lie
      on the sigma 70 subunit, within a "contact site II", which extends at least from
      conserved region 3.2 to the upstream end of region 4.2. Moreover, as in the case
      of contact site I on the alpha subunit, it appears that contact site II contains
      various different subsites for interaction with specific class II activators, and
      that PhoB and CRP require distinct subsites.

PMID- 8289271
TI  - recA-independent and recA-dependent intramolecular plasmid recombination.
      Differential homology requirement and distance effect.
AB  - We show that recombination between directly repeated sequences in plasmids occurs
      via both recA-independent and recA-dependent mechanisms in Escherichia coli. They
      are differentially affected by two factors, the distance separating the
      homologies and the size of the homology. Recombination between tandem
      duplications up to 300 base-pairs shows virtually no recA dependence. Increasing
      the size of the duplications beyond 300 base-pairs gradually increases the recA
      dependence. Furthermore, insertion of a sizable DNA sequence in between the
      duplications, substantially increases the recA dependence. We conclude that
      increasing the distance separating the homologous regions preferentially inhibits
      the recA-independent recombination. On the other hand, shortening of the homology
      preferentially inhibits recA-dependent recombination. Consequently, recombination
      between short tandem duplications is totally recA-independent.

PMID- 8289272
TI  - A dominant negative allele of the Escherichia coli uvrD gene encoding DNA
      helicase II. A biochemical and genetic characterization.
AB  - A site-specific lysine to methionine mutation has been engineered at the
      invariant Lys35 residue in the ATPase A binding site of the Escherichia coli uvrD
      gene encoding DNA helicase II. The mutant protein (UvrDK35M) has been purified to
      apparent homogeneity and characterized. The kcat for DNA-dependent ATP hydrolysis
      was less than 0.5% that of the wild-type enzyme with no change in the apparent Km
      for ATP. No unwinding of partial duplex DNA substrates could be detected using
      the mutant protein. Moreover, the mutant protein inhibited the unwinding reaction
      catalyzed by the wild-type protein at ratios of mutant enzyme to wild-type enzyme
      < 1. We conclude that the K35M mutation renders helicase II catalytically
      inactive as a DNA helicase with little or no effect on the ability of the enzyme
      to bind ATP, DNA, or other proteins. In vivo complementation assays indicate that
      the mutant protein cannot substitute for the wild-type protein in methyl-directed
      mismatch repair, suggesting that the ATPase and/or helicase activity of helicase
      II is required in this repair pathway. Additional genetic characterization of the
      uvrDK35M allele, supplied on a plasmid, suggests that expression of the mutant
      protein, at levels equivalent to that of the wild-type protein, results in a
      dominant negative phenotype. Expression of lower levels of the mutant protein,
      both in the presence and absence of wild-type helicase II, results in a
      constitutive induction of the cellular SOS response and extensive filamentation
      of cells. This induction of the SOS response is not due to a defect in methyl
      directed mismatch repair. Taken together, these data are consistent with the
      notion that E. coli helicase II may have a role in DNA replication.

PMID- 8289273
TI  - Linker insertion mutagenesis of Drosophila topoisomerase II. Probing the
      structure of eukaryotic topoisomerase II.
AB  - The sequences of all type II DNA topoisomerases, and possibly some of their key
      structural features, are conserved. The N-terminal and middle regions of the
      eukaryotic DNA topoisomerase II are homologous to the bacterial gyrase subunits B
      and A, respectively, and the hydrophilic C-terminal region is more divergent
      among these enzymes. To gain further insights into the structure of eukaryotic
      topoisomerase II, we constructed 23 linker insertion mutants of Drosophila DNA
      topoisomerase II. These mutant proteins were expressed in a heterologous yeast
      system, in which we have previously demonstrated that Drosophila DNA
      topoisomerase II could be functionally expressed and complement yeast top2
      mutations. The linker insertion mutants were characterized genetically by testing
      for complementation of yeast top2ts mutation at the non-permissive temperature
      and complementation of yeast top2 null mutation using a color sector assay. We
      also partially purified the mutant proteins and examined their enzymatic activity
      by unknotting the P4 knotted DNA. There appears to be a good correlation between
      the in vivo and in vitro activities. There are nine fully active, six partially
      active, and eight negative linker insertion mutants. All five linker insertion
      mutants in the C-terminal region are active and two linker insertion mutants
      located in the junction of the two regions homologous to gyrB/gyrA subunits are
      also active. In addition, we also mapped the trypsin-sensitive sites in
      Drosophila DNA topoisomerase II. The C-terminal region is extremely sensitive to
      trypsin digestion. Another major trypsin-sensitive site is located between Lys406
      and Thr407, which is near the protease sites also observed in the bacterial gyrB
      subunit and yeast topoisomerase II. We discuss the possible structural and
      functional implications of these results.

PMID- 8289274
TI  - Genetic organization of the conjugal DNA processing region of the IncW plasmid
      R388.
AB  - The region of the IncW plasmid R388 involved in conjugal DNA metabolism and
      mobilization (MOBw) has been analyzed by Tn5tac1 insertion mutagenesis, genetic
      complementation and DNA sequencing. Three genes (trwA, trwB and trwC) were mapped
      within MOBw. They are transcribed from the same strand and away from oriT. The
      predicted products of trwA, trwB and trwC are proteins of 121, 507 and 966 amino
      acids, respectively. The three proteins were visualized in a minicell expression
      system, showing apparent molecular masses of 13.5, 55 and 105 kDa, respectively.
      The deduced amino acid sequence of TrwA shows significant similarity to TraJ of
      the IncP plasmids RP4 and R751, to NikA of the IncI plasmid R64 and to MobB of
      plasmid pTF-FC2. The amino acid sequence of TrwB predicts an integral membrane
      protein which contains an NTP-binding motif. It shows 28% to 29% identity with
      TraD of plasmids F and R100, 23% identity with TraG of plasmids RP4 and R751 and
      20% identity with VirD4 of the Ti plasmids of Agrobacterium tumefaciens. The
      amino acid sequence of TrwC shows the characteristic motifs of the Rep family of
      DNA helicases. It shows 33% identity with the sequence of helicase I (TraI) of
      plasmid F. The similarity is highest in the N-terminal segments of the proteins,
      which show conservation of characteristic amino acid motifs of a family of DNA
      relaxases, including VirD2 of the Ti plasmid. The conserved features of these
      three proteins among the different transfer systems suggest that a very
      widespread conjugal DNA mobilization mechanism is shared by the transfer
      apparatuses of IncF, IncI, IncP, IncW and Ti plasmids.

PMID- 8289275
TI  - Accuracy of replication past the T-C (6-4) adduct.
AB  - The thymine-cytosine pyrimidine-pyrimidone (6-4) adduct has variously been
      predicted to be among the most and among the least mutagenic of the ultraviolet
      light photoproducts. We have therefore investigated the frequency and accuracy of
      DNA replication past this lesion, using a single-stranded M13mp7-based vector
      with a uniquely located example of this lesion transfected into SOS-induced and
      uninduced cells of a uvr A6 strain of Escherichia coli. Both the UVC T-C (6-4)
      adduct and its Dewar valence (UVB) photoisomer were studied. Random samples from
      non-selective collections of progeny phage were sequenced to determine the nature
      of the replication events that occurred at or near the site of template damage
      under SOS conditions. The UVC (6-4) adduct was found to be much less mutagenic
      than its T-T counterpart, but still much more mutagenic than a cyclobutane dimer;
      34% (71 out of 206) of all bypass events yielded mutations, of which all were
      targeted and 80% (57 out of 71) were 3' C-->T transitions. The Dewar valence
      photoisomer exhibited reduced specificity and enhanced mutagenicity; 79% (183 out
      of 233) of the phage progeny were mutants, of which all but one were targeted and
      45% (83 out of 183) were 3' C-->T transitions. For the most part, these results
      are consistent with a model postulating base-pairing between the pyrimidinone (of
      either the C or T variety) and guanine, via hydrogen bonds at N-3 and O-2 in the
      UVC, but not the Dewar, isomer. The occurrence of the 3' C-->T transitions, not
      predicted by this model, shows however that the absence of a methyl group at C-5
      also has a significant influence on mutation induction. Both isomers were
      efficient blocks to replication; less than 1% of these vectors could be
      replicated in uninduced cells. Following SOS induction the frequency of bypass
      increased to 24.5% and 12.5% for the UVC and the Dewar isomers, respectively.

PMID- 8289276
TI  - A Caulobacter DNA methyltransferase that functions only in the predivisional
      cell.
AB  - Caulobacter crescentus was found to have a DNA methyltransferase, CcrM, that
      methylates the adenine base of the HinfI recognition sequence, GANTC. The ccrM
      gene was cloned, and DNA sequence analysis revealed that the predicted amino acid
      sequence has 49% identity with the Haemophilus influenzae methyltransferase
      HinfM. Expression of the ccrM gene was found to be restricted to the portion of
      the cell cycle immediately prior to cell division. At three separate chromosomal
      sites the CcrM recognition sequence is fully methylated in swarmer cells, becomes
      hemimethylated upon DNA replication in stalked cells, and does not become
      remethylated until just prior to cell division. The time of methyltransferase
      expression coincides with the time of methylation of these three chromosomal
      sites and of plasmid DNA in the predivisional cell. When ccrM gene expression is
      placed under control of a constitutive promoter, these chromosomal sites are
      fully methylated throughout the cell cycle. A high proportion of morphologically
      aberrant cells, and cells that have undergone an additional chromosome
      replication initiation, are found in this population. Thus, the temporal control
      of this methyltransferase appears to contribute to the accurate cell-cycle
      control of DNA replication and cellular morphology.

PMID- 8289277
TI  - Interaction of Tn5 transposase with the transposon termini.
AB  - Transposition of Tn5 requires the binding of the transposase protein to the
      transposon outside end (OE) DNA sequences. Transposase mutants that increase the
      transposition frequency result in the formation of two distinct transposase/OE
      DNA complexes, observed by gel retardation analysis. The slower migrating complex
      I, also formed by wild-type transposase, contains protein oligomers of
      transposase and transposase related proteins. The faster migrating, novel complex
      II is caused by the binding of monomeric, proteolytic transposase fragments gamma
      and delta that have lost the carboxy-terminus of the protein. Transposase gamma
      and delta bind OE DNA with a high apparent affinity but are unable to promote
      transposition in vivo. We propose that the transposase protein is functionally
      unstable and can undergo a conformational change that reduces the activity but
      protects the protein from proteolysis. The transposase mutants favor the more
      active but proteolytically hypersensitive protein conformation.

PMID- 8289278
TI  - DNA helical instability facilitates initiation at the SV40 replication origin.
AB  - Previous analysis of mutations in bacterial and yeast replication origins has
      identified a genetic component, termed a DNA unwinding element (DUE), whose
      intrinsic helical instability is essential for origin function. For the SV40
      replication origin, we show here that the early palindrome (EP) and A + T-rich
      (AT) domains both exhibit helical instability, despite their dissimilar A + T
      compositions. To test the possible contribution of helical instability to SV40
      origin function, the relationship between helical stability of mutant origin
      sequences and their known origin activity in vitro and in vivo was examined.
      Origin activity correlates inversely with the helical stability of mutations
      within the EP domain but not the AT domain or the T-antigen binding domain. The
      quantitative correlation holds for four different measures of origin activity
      determined in vitro and in vivo. An even better-correlated collection of
      mutations was found in a specific portion of the EP domain. This specific EP
      subdomain coincides with the sequence known to be strand-separated after T
      antigen binds the origin in vitro and with the origin of bidirectional
      replication in vivo. Our analysis of origin mutations indicates that the helical
      instability of the specific EP subdomain is required to facilitate T-antigen
      induced melting and the initiation of DNA replication. The sensitivity of the
      required EP subdomain to mutations that stabilize the DNA helix defines the DUE
      of the SV40 replication origin.

PMID- 8289279
TI  - Solution structure of the 3'-end of brome mosaic virus genomic RNAs.
      Conformational mimicry with canonical tRNAs.
AB  - The conformation of the last 201 nucleotides located at the 3'-end of brome
      mosaic virus (BMV) RNAs was investigated in solution using different chemical and
      enzymatic probes. Bases were probed with dimethylsulfate (which methylates N-1
      positions of A, N-3 positions of C and N-7 positions of G), a carbodiimide (which
      modifies N-1 positions of G and N-3 positions of U) and diethylpyrocarbonate
      (which modifies N-7 positions of A). Ribonucleases T1, U2 and S1 were used to map
      unpaired nucleotides and ribonuclease V1 to monitor paired bases or stacked
      nucleotides. Cleavage or modification sites were detected by gel electrophoresis
      either indirectly by analyzing DNA sequence patterns generated by primer
      extension with reverse transcriptase of the modified RNAs or by direct
      identification within the statistical cleavage patterns of the RNA. On the basis
      of these biochemical results, an atomic model was built by computer modeling and
      its stereochemistry refined. The deduced secondary structure of the RNA confirms
      data previously proposed by others but contains additional base-pairs (A27-U32,
      A28-G31, G41-A134, G64-C68, U80-A99, G81-A98, G88-U91, G100-U126, U104-U125, G162
      G166 and A172-A191), one new tertiary long-range interaction (U103-U164) and a
      small triple helical conformation with (G41-A134)-A18 and (C42-G133)-A17
      interactions. The new secondary structure also indicates the existence of a
      second pseudoknot involving pairing between residues A181 to A184 and residues
      U197 to U194, outside the domain conferring tyrosylation ability to BMV RNA. The
      main outcome from the model stems from its intricate folding, which allows a new
      assignment for the domains mimicking the anticodon- and D-loop regions of tRNA.
      Interestingly, the stem and loop region found structurally to be analogous to the
      anticodon arm of tRNA(Tyr) does not contain the tyrosine anticodon involved in
      the aminoacylation process. The structural analogies with canonical tRNA(Tyr)
      illustrate the functional mimicry existing between the BMV RNA structure and
      canonical tRNA(Tyr) that allows for their efficient aminoacylation by tyrosyl
      tRNA synthetase. This structural model rationalizes mutagenic and footprinting
      data that have established the importance of specific regions of the viral RNA
      for recognition by its replicase, (ATP,CTP):tRNA nucleotidyl-transferase and
      yeast tyrosyl-tRNA synthetase. The new fold has biological implications that can
      be used as a predictive tool for elaborating new experiments.

PMID- 8289280
TI  - Cooperative DNA-protein interactions. Effects of changing the spacing between
      adjacent binding sites.
AB  - Cooperative binding of specific DNA-binding proteins plays crucial roles in gene
      regulatory circuitry, and is a model system for interactions between proteins
      bound to DNA. We have studied coliphage HK022 repressor, which binds to two
      adjacent operators with a cooperativity parameter of approximately 2000. We
      examined the effect of changing the spacing between these two operators on
      cooperativity and on the conformation of the complex. Maximum cooperativity was
      seen with the wild-type spacing; considerable cooperativity was retained for most
      spacing variants, but was abolished when the operators lay on opposite faces of
      the DNA helix. Most spacing variants conferred changes in the conformation of the
      DNA-protein complex. Our data indicate that the pairwise cooperativity observed
      with the wild-type spacing results from a conformation that prevents protein
      protein contacts with flanking bound dimers. We conclude that protein-DNA
      complexes involving the same specific binding sites and the same protein
      molecules can adopt many different conformations, depending on the spacing
      between the binding sites. This conclusion may be broadly applicable to protein
      DNA interactions in other systems.

PMID- 8289281
TI  - Ligand-induced conformational states of the cytosine-specific DNA
      methyltransferase M.HgaI-2.
AB  - The interaction of one of the two DNA methyltransferases encoded by the HgaI
      restriction and modification system, M.HgaI-2, with substrates and substrate
      analogues is described. Circular dichroism spectroscopy has been used to
      demonstrate that addition of the methyl donor, S-adenosyl-L-methionine and the
      inhibitory substrate analogue sinefungin, both induce conformational transitions
      in the protein in the absence of DNA. Moreover, the addition of DNA is shown to
      enhance the apparent secondary structure of M.HgaI-2 whilst addition of
      sinefungin or S-adenosyl-L-methionine reduces apparent secondary structure. The
      circular dichroism spectrum of the abortive complex between the enzyme, DNA and
      sinefungin is dominated by the conformational properties of the binary complex of
      enzyme and sinefungin alone. Addition of a specific oligodeoxynucleotide duplex
      in which the target cytosine is replaced by a pyrimidinone, leads to a further
      ligand induced conformational transition as determined by electrophoretic
      analysis. The addition of sinefungin, or S-adenosyl-L-methionine, to M.HgaI-2
      bound to the reactive oligodeoxynucleotide duplex, leads to yet another
      conformational transition in the protein as determined by the differential
      susceptibility of ternary and binary complexes to proteolysis. These experiments
      identify at least six ligand-inducible conformational states of M.HgaI-2 and, in
      view of the sequence similarity amongst this class of enzymes, suggest that
      conformational flexibility is a general feature of C-5 cytosine-specific DNA
      methyltransferases. Moreover, the substitution of the target cytosine by a
      pyrimidinone mimics the effect of 5-azacytosine incorporation into DNA.

PMID- 8289282
TI  - The refined three-dimensional structure of an insect virus at 2.8 A resolution.
AB  - The structure of the black beetle nodavirus has been refined at 2.8 A resolution
      by alternate use of restrained least-squares atomic coordinate refinement and
      phase refinement by real space averaging with the 5-fold non-crystallographic
      symmetry in the crystal. The coordinates were also refined by simulated
      annealing. The final R-factor for all data with I/sigma(I) > 4 was 22.1%. A total
      of 7692 atoms were refined in one icosahedral asymmetric unit which included 273
      oxygen atoms of ordered water molecules. Three identical gene products of 407
      amino acids form one icosahedral asymmetric unit. Each is located in a
      structurally unique position, identified as A, B or C, consistent with a T = 3
      quasi equivalent lattice. Icosahedral pentamers are formed by A subunits while B
      and C subunits alternate about icosahedral 3-fold axes to form quasi hexamers.
      Five calcium ions are located within the icosahedral asymmetric unit and
      stabilize the quasi 3-fold related intersubunit contacts between A, B and C. The
      final model consists of coordinates for residues 56 to 379 of all three subunits
      and residues 20 to 31 from the C subunit only. Atom positions for the sugar
      phosphate backbone were modeled for ten nucleotides close to the icosahedral 2
      fold axes. Symmetry equivalent polyribonucleotides form a helical duplex at each
      icosahedral 2-fold axis. The three subunits display an eight-stranded beta-barrel
      fold, very similar to the subunit structures observed in most other icosahedral
      RNA viruses analyzed. Quasi equivalence is regulated by the ordered RNA and
      residues 20 to 31 in the C subunit to form a "flat inter subunit contact" at
      icosahedral 2-fold joints. The RNA and polypeptide are disordered at the quasi 2
      fold joints and this results in a "bent inter subunit contact". Although similar
      quaternary structures were seen in T = 3 plant viruses studied, RNA did not play
      a role as a molecular switch in those structures. The autocatalytic, post
      assembly, cleavage of the initial gene product at residue Asn363/Ala364 to form a
      stable and infectious particle is probably the result of an acid catalyzed main
      chain hydrolysis in which Asp75 is the proton donor. The reaction is initiated by
      assembly which places Asp75 in a hydrophobic environment created by quaternary
      interactions which raises its pK to 5.6. The region in which the reaction occurs
      is formed by an internal helical bundle that has not been seen in other virus
      structures.

PMID- 8289283
TI  - Characterization of a trifluoroethanol-induced partially folded state of alpha
      lactalbumin.
AB  - The protein alpha-lactalbumin exists in a partially folded molten globule state
      at pH 2.0, the A state. This state is believed to be compact, possessing a
      similar amount of secondary structure to the native state but having a flexible
      tertiary structure comprised mainly of non-specific hydrophobic clustering of
      residues. Addition of trifluoroethanol (TFE) to bovine, human and guinea pig
      alpha-lactalbumin at pH 2.0 has been found in each case to induce a
      conformational transition in the A state as monitored by circular dichroism,
      nuclear magnetic resonance chemical shifts, and 1-anilinonaphthalene-8-sulphonate
      binding. The mid-point of this transition is near 15% (v/v) TFE and is
      effectively complete by 50% (v/v) TFE at 315 K. Far ultraviolet circular
      dichroism ellipticities at 208 nm and 220 nm, usually taken as a measure of the
      degree of helical character, are substantially more negative in the TFE state
      than in the A state. Furthermore, backbone amide protons protected from solvent
      exchange in the A state are generally at least as strongly protected in the TFE
      state; patterns of protection appear similar in the two states and include at
      least part of both the B and C alpha-helices. One major difference from the A
      state is nevertheless evident: the ability to bind the fluorescent probe 1
      anilinonaphthalene-8-sulphonate, characteristic of molten globule states, is lost
      in the TFE state. Like the A state, the TFE state of alpha-lactalbumin shows
      little chemical shift dispersion of side-chain resonances. Extensive line
      broadening in the nuclear magnetic resonance spectra, characteristic of slow
      conformational averaging in the A state, is, however, much reduced in the TFE
      state. The line narrowing observed in the TFE state has made it possible to
      obtain directly sequence-specific assignments for about 25% of the 123 residues
      of bovine alpha-lactalbumin in 50% (v/v) TFE. Two helices are amongst regions of
      structure so far identified from short-range backbone nuclear Overhauser
      enhancement (NOE) connectivities in two-dimensional spectra of the TFE state. One
      of the helices (residues 86 to 96) corresponds to the C-helix in the native
      structure. The other (residues 35 to 41) corresponds, however, to a region of the
      sequence that is not helical in the native state. The partially folded state of
      alpha-lactalbumin formed in TFE, therefore, supports both native and non-native
      secondary structure in the absence of persistent long-range tertiary structure.

PMID- 8289284
TI  - Determination of alpha-helix propensity within the context of a folded protein.
      Sites 44 and 131 in bacteriophage T4 lysozyme.
AB  - To determine the effects of different amino acids on the structure and stability
      of an alpha-helix in the context of a globular protein, all 19 naturally
      occurring amino acids were substituted for Ser44 in phage T4 lysozyme. A more
      restricted set of nine replacements was also made for Val131. Ser44 and Val131
      are two of a very limited number of possible sites in T4 lysozyme that are well
      within alpha-helices, are solvent-exposed and relatively free of interactions
      with neighboring residues, and are not involved in crystal contacts. High
      resolution structures for the majority of the mutants, some of which crystallized
      non-isomorphously with wild-type, were determined. With the exception of proline,
      the amino acid substitutions caused little if any perturbation of the alpha-helix
      backbone. Also the beta-branched residues Thr, Val and Ile show no indication of
      either side-chain or backbone distortion. Therefore, other than proline, there is
      no evidence that differences in helix propensities are associated with different
      amounts of strain introduced into the helix. For reference, and also to allow
      estimates of side-chain entropy, a survey was made of side-chain conformations in
      100 well-refined protein structures. As noted previously all side-chains within
      alpha-helices strongly avoid the g- conformation (chi 1 approximately 60
      degrees). This restricts the beta-branched residues Thr, Val and Ile to a single
      conformer (g+, chi 1 approximately -60 degrees). Asp, Asn, Met and Ser within
      helices also overwhelmingly prefer the g+ conformation. For Arg, Cys, Gln, Glu,
      Leu and Lys the t (chi 1 approximately 180 degrees) and g+ conformers are
      populated roughly equally. Only the aromatic residues, His, Tyr, Trp and Phe
      prefer the t conformation. These preferences are the same whether the side-chain
      is buried or solvent-exposed. In general, the side-chain conformations adopted by
      the residues substituted at positions 44 and 131 correspond to the most commonly
      observed conformation for the same amino acid in helices in known protein
      structures. The changes in protein stability for the replacements at site 131 in
      general agree well with those at site 44 (correlation r = 0.97), suggesting that
      these may be representative of substitutions at fully solvent-exposed sites in
      the middle of alpha-helices. The free energy values also agree quite well with
      those observed for equivalent replacements in a number of soluble alpha-helical
      model peptides and with data from "host-guest" studies and statistical surveys (r
      = 0.69 to 0.93).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8289285
TI  - Significance of root-mean-square deviation in comparing three-dimensional
      structures of globular proteins.
AB  - In the study of globular protein conformations, one customarily measures the
      similarity in three-dimensional structure by the root-mean-square deviation
      (RMSD) of the C alpha atomic coordinates after optimal rigid body superposition.
      Even when the two protein structures each consist of a single chain having the
      same number of residues so that the matching of C alpha atoms is obvious, it is
      not clear how to interpret the RMSD. A very large value means they are
      dissimilar, and zero means they are identical in conformation, but at what
      intermediate values are they particularly similar or clearly dissimilar? While
      many workers in the field have chosen arbitrary cutoffs, and others have judged
      values of RMSD according to the observed distribution of RMSD for random
      structures, we propose a self-referential, non-statistical standard. We take two
      conformers to be intrinsically similar if their RMSD is smaller than that when
      one of them is mirror inverted. Because the structures considered here are not
      arbitrary configurations of point atoms, but are compact, globular, polypeptide
      chains, our definition is closely related to similarity in radius of gyration and
      overall chain folding patterns. Being strongly similar in our sense implies that
      the radii of gyration must be nearly identical, the root-mean-square deviation in
      interatomic distances is linearly related to RMSD, and the two chains must have
      the same general fold. Only when the RMSD exceeds this level can parts of the
      polypeptide chain undergo nontrivial rearrangements while remaining globular.
      This enables us to judge when a prediction of a protein's conformation is
      "correct except for minor perturbations", or when the ensemble of protein
      structures deduced from NMR experiments are "basically in mutual agreement".

PMID- 8289286
TI  - Cytidine deaminase. The 2.3 A crystal structure of an enzyme: transition-state
      analog complex.
AB  - We have solved the structure of Escherichia coli cytidine deaminase (CDA)
      complexed to the transition state analog, 5-fluoroprimidin-2-one riboside. The
      monomer of the alpha 2 CDA dimer is composed of a small N-terminal alpha-helical
      domain with no obvious connection to the active sites, and two, larger, core
      domains. The two core domains have nearly identical tertiary structures and are
      related by approximate 2-fold symmetry, but lack internal amino acid sequence
      homology. Comparison of the core domain structure with known structures by
      sequence homology and structural compatibility searches suggests that the CDA
      tertiary structure cannot be superimposed on any known protein structure. The two
      active sites per dimer are formed across the subunit interface. The N-terminal
      core domain provides a pyrimidine nucleoside and zinc-binding pocket and the
      structurally homologous C-terminal core domain in the other monomer covers this
      active-site cleft, completely sequestering the ligand from solvent. The deeply
      buried zinc-binding site is formed by a novel "topological switch point" at the
      amino termini of two alpha-helices in consecutive alpha-beta-alpha-beta segments.
      The transition state analog is bound as a covalent hydrate at C4. The inhibitor
      hydroxyl oxygen atom interacts both with the zinc atom and the Glu104 carboxylate
      group, affording high differential affinity for the hydroxyl group relative to a
      hydrogen atom, in a manner reminiscent of that observed in adenosine deaminase
      (ADA). Unlike the latter enzyme, the zinc atom is coordinated in a tetrahedral
      ligand field to two cysteine and one histidine ligands, plus the hydroxyl group.
      Moreover, the inhibitor stereochemistry is of the opposite hand from that of the
      corresponding ADA inhibitor at C4(R), but is the same at the hydroxyl group
      O4(S). A consequence of these stereochemical differences is that in CDA a single
      conserved carboxylate side-chain, Glu104, can provide all of the necessary proton
      transfer functions involved in generating the zinc hydroxide nucleophile, and
      protonating the pyrimidine ring nitrogen atom and leaving amino group. The
      differences in zinc ligands, ligand-binding stereochemistry, and tertiary
      structures of CDA and ADA strongly suggest that the common features of transition
      state stabilization arose by convergent evolution.

PMID- 8289287
TI  - High-resolution crystallographic analysis of a co-operative dimeric hemoglobin.
AB  - High-resolution crystal structures of the co-operative dimeric hemoglobin from
      the blood clam Scapharca inaequivalvis have been determined in the unliganded
      (deoxy) and carbon monoxide (CO) liganded states. The deoxy structure has been
      refined at 1.6 A resolution to an R-factor of 0.158 and the CO structure has been
      refined at 1.4 A resolution to an R-factor of 0.159. These structures reveal
      details of the structural transitions involved in co-operative ligand binding
      that involve only a minor rotation of subunits but very striking tertiary changes
      at the interface. A small number of residues in the F-helix appear to mediate co
      operativity in this simple hemoglobin. The oxygen affinity of each subunit
      appears to be largely dictated by the disposition of phenylalanine 97, whose side
      chain packs in the heme pocket in the deoxy state but is extruded towards the
      interface in the CO-liganded structure. Direct involvement of the ligand-binding
      heme group is a novel feature of the subunit interface and appears important for
      intersubunit communication. Ligation alters the conformation of the heme
      propionate groups along with two interacting residues from the symmetry-related
      subunit. These two residues, lysine 96 and asparagine 100, link the heme of one
      subunit with the F-helix of the second subunit in such a way as to influence the
      ligand affinity of that subunit. The interface is highly hydrated by well-ordered
      water molecules that are likely to be important in the stabilization of the two
      structures.

PMID- 8289288
TI  - Backbone flexibility and stability of reverse turn conformation in a model
      system.
AB  - Molecular dynamics simulations have been used to study differences in propensity
      to form a disulfide-bridged turn conformation by peptides with sequence Ac-Cys
      Pro-Xaa-Cys-NMe. The calculations were limited to three peptides, with Xaa = Aib,
      Gly and Val. The experimental differences in propensity (in terms of free energy
      differences delta delta G degree) were reproduced within 2 kJ/mol. The use of a
      reduced 1-4 non-bonded interaction potential was tested in this system, but was
      found to give slightly worse agreement with experiment. The stability of
      alternate conformations was determined systematically. Type I and II turn
      conformations of the Aib compound have similar free energy; the Val compound is
      most stable in a type I turn conformation (by 8 kJ/mol), while the Gly compound
      is most stable in a type II turn conformation (by 5 kJ/mol). Different backbone
      conformations were obtained for the valine compound in simulations in solution
      and in the crystal. It is concluded that turn conformations with psi i+2 near 0,
      as typically seen in proteins, are stabilized by intramolecular hydrogen bonding
      in the confined environment. However, when exposed to solvent, hydrogen bonds
      with water stabilize conformations with larger or smaller values of psi i+2 that
      are more similar to free energy minima in the isolated, terminally blocked,
      residue.

PMID- 8289289
TI  - Structure of human factor D. A complement system protein at 2.0 A resolution.
AB  - Factor D, an essential enzyme for the activation of the alternative pathway of
      the complement system, belongs to the serine protease superfamily. The crystal
      structure of the enzyme was solved by a combination of multiple isomorphous
      replacement and molecular replacement methods. The present model was refined to
      an R-factor of 18.8% using 23,681 observed reflections between 7.5 and 2.0 A
      resolution, with a root-mean-square deviation from standard bond lengths of 0.016
      A. The two non-crystallographically related molecules in the triclinic unit cell
      have distinctive active site conformations. The protein has the general
      structural fold of a serine protease, but there are several unique amino acid
      substitutions resulting in significant alterations in the critical loops
      responsible for catalysis and substrate specificity in serine proteases. Factor D
      is the first complement serine protease whose three-dimensional structure has
      been determined.

PMID- 8289290
TI  - Planar stacking interactions of arginine and aromatic side-chains in proteins.
AB  - A parallel stacking arrangement of the guanidinium groups of arginines directly
      over the center of the rings of aromatic side-chains is observed much more
      frequently in proteins than would be expected by chance. This type of
      interaction, which is often found in locations critical to the function,
      apparently serves to orient the arginine side-chain without interfering with its
      ability to form hydrogen bonds elsewhere. It is distinct from the interactions
      which involve the side-chains of asparagine or glutamine, which do frequently
      assume a nearly planar relationship to the ring, but at a position at or beyond
      the ring edge.

PMID- 8289291
TI  - Refined crystal structure of rat parvalbumin, a mammalian alpha-lineage
      parvalbumin, at 2.0 A resolution.
AB  - We present here the X-ray crystal structure of the rat alpha-parvalbumin from
      fast twitch muscle. This protein (M(r) 11.8 kDa) crystallizes in space group
      P2(1)2(1)2(1) with unit cell dimensions of a = 34.3 A, b = 55.0 A, c = 156.1 A
      and three molecules in the asymmetric unit. The protein structure was solved by
      the molecular replacement method and has been refined to a crystallographic R
      factor [formula: see text] of 0.181 for all reflections with I/sigma(I) > or = 2
      (I = intensity) between 8.0 and 2.0 A resolution. The molecules located most
      easily in the molecular replacement rotation function had lower overall thermal
      motion parameters and higher numbers of intermolecular crystal packing contacts.
      The overall fold of the polypeptide chain for the rat alpha-parvalbumin is
      similar to other known parvalbumin structures (root-mean-square deviations in
      alpha-carbon atom positions range from 0.60 to 0.87 A). There are two Ca(2+)
      binding sites in parvalbumins, and there is some evidence for a third ion-binding
      site, adjacent to the CD site, in the rat species. The level of structural
      variability among the best-ordered regions of the three independent rat alpha
      parvalbumin molecules in the crystallographic asymmetric unit is two to three
      times higher than the mean coordinate error (0.10 A), indicating flexibility in
      the molecule. Sequence differences between alpha and beta-lineage parvalbumins
      result in repacking of the hydrophobic core and some shifts in the protein
      backbone. The shifts are localized, however, and entire helices do not shift as
      rigid units.

PMID- 8289292
TI  - Molecular recognition by thrombin. Role of the slow-->fast transition, site
      specific ion binding energetics and thermodynamic mapping of structural
      components.
AB  - The interaction of thrombin with the potent natural inhibitor hirudin is
      controlled in a complex fashion by the binding of Na+ and Cl- to the enzyme and
      allosteric transitions. Binding of hirudin is positively linked to Na+ binding,
      but is opposed in a competitive fashion by the binding of Cl-. Since Na+ binding
      induces the slow-->fast transition of thrombin, it follows from linkage
      principles that hirudin binds to the fast form with higher affinity. Hence, the
      slow-->fast transition is a key component of molecular recognition of hirudin by
      thrombin. We propose a three-step mechanism for molecular recognition of hirudin
      by thrombin, which is also relevant for recognition of fibrinogen and possibly
      the platelet receptor and thrombomodulin. First, the C-terminal acidic tail of
      hirudin binds to the fibrinogen recognition site of thrombin displacing one Cl
      ion from the thrombin surface. Then, the enzyme undergoes a conformational
      transition that gives rise to increased accessibility of the catalytic pocket to
      small synthetic substrates through movement of the Trp148 loop. The changes in
      the catalytic moiety triggered allosterically by binding to the fibrinogen
      recognition site are linked to the uptake of Na+ and are similar to, if not
      identical with, those observed in the Na(+)-induced slow-->fast transition.
      Finally, the compact N-terminal domain is accommodated in the region surrounding
      the catalytic pocket. Hirudin binding is also used as a probe of site-specific
      ion-binding interactions of Na+ and Cl- with the enzyme, characterized by
      cooperativity between the Na+ and Cl- binding domains. The structural components
      directly involved or linked to Na+ and Cl- binding have been explored in terms of
      free energy perturbations of the binding of hirudin and a number of ligands. The
      fibrinogen recognition site stores most of the free energy of coupling with Cl-
      binding, while regions surrounding the access to the catalytic pocket provide
      most of the free energy of coupling with Na+ binding and the slow-->fast
      transition of thrombin. It is concluded that thrombin is an allosteric enzyme
      that exists in two forms, slow and fast, and that the allosteric transition slow-
      >fast represents the key element of molecular recognition of important
      physiological substrates. The allosteric nature of the enzyme also enables
      different structural domains to communicate and give rise to biological function.

PMID- 8289293
TI  - Crystallization and preliminary crystallographic analysis of sfericase. A
      Bacillus sphaericus calcium-dependent serine proteinase.
AB  - Sfericase is an important intracellular proteinase produced by Bacillus
      sphaericus in the stationary phase of growth. It is a Ca(2+)-dependent serine
      proteinase with optimal activity at pH 9.0 to 9.3. The molecular mass of
      sfericase is 32 kDa, as determined by sedimentation equilibrium. It seems to be
      involved in the interplay of various elements of the mosquitocidal activity of B.
      sphaericus, and hence is important for biological mosquito control. Sfericase
      significantly reduces viscosity of human pathological bronchial secretions and
      has recently shown good clinical effects in treatment of bronchitis, pneumonia
      and sinusitis. This enzyme was isolated from B. sphaericus and single crystals
      were obtained by the hanging drop vapor diffusion method. The crystals belong to
      the monoclinic space group P2, with cell dimensions of a = 46.94 A, b = 64.55 A,
      c = 86.23 A and beta = 95.4 degrees. These crystals are mechanically strong, they
      are stable in the X-ray beam and they diffract to better than 1.8 A resolution.
      The cell dimensions are consistent with four molecules per unit cell and two
      molecules in the asymmetric unit. A complete native data set to 1.77 A resolution
      has been collected on a Rigaku R-AXIS-IIc Imaging Plate Detector system and a
      heavy-atom derivative search is presently in progress.

PMID- 8289294
TI  - Co-crystallization of the catalytic subunit of the serine/threonine specific
      protein phosphatase 1 from human in complex with microcystin LR.
AB  - The catalytic subunit of the serine/threonine specific protein phosphatase 1 from
      human (molecular mass 37 KDa) has been co-crystallized in complex with the
      cyanobacterial toxin microcystin LR (molecular mass 1 kDa). The crystals diffract
      to a resolution of 2.8 A when exposed to synchrotron radiation and belong to
      space group P2(1)2(1)2 with a = 109.5 A, b = 90.6 A, c = 38.7 A. There is one
      molecule of protein phosphatase 1 per asymmetric unit. The crystal form is
      suitable for the determination of the atomic structure of protein phosphatase 1.

PMID- 8289295
TI  - Crystallization and preliminary X-ray analysis of C-reactive protein from rat.
AB  - Crystals of C-reactive protein from rat have been grown both with and without
      calcium. Two major components of the protein have been resolved on the basis of
      their calcium-dependent fine specificity for monophosphate esters. Crystals grown
      without calcium are tetragonal, space group P42(1)2 with unit cell parameters a =
      b = 163.81(9)A and c = 125.21(6)A, and diffract X-rays to 3.0 A resolution. The
      rotation function specifies a molecular 5-fold symmetry axis at 24 degrees away
      from c in the (110) plane.

PMID- 8289296
TI  - Crystallographic characterization of pertactin, a membrane-associated protein
      from Bordetella pertussis.
AB  - Pertactin, a membrane-associated protein of Bordetella pertussis, has been
      crystallized in the presence of 28% ammonium sulphate. The space group is P6(3)22
      with cell dimensions a = b = 178.2 A and c = 106.8 A. The crystals diffract to
      3.3 A using a rotating anode source and are suitable for an X-ray structure
      determination. Assuming one molecule in the asymmetric unit, 70% of the cell is
      occupied by solvent.

PMID- 8289297
TI  - Sequence and crystallization of Escherichia coli dethiobiotin synthetase, the
      penultimate enzyme of biotin biosynthesis.
AB  - The enzyme dethiobiotin synthetase (EC 6.3.3.3) has been cloned and over
      expressed in Escherichia coli in such a way that milligram quantities are
      available. The purified enzyme has been subjected to a number of physical and
      chemical studies, sequenced and most notably it has been crystallized in a form
      that is suitable for X-ray structure determination. The cell dimensions are a =
      72.8 A, b = 49.2 A, c = 61.4 A, beta = 106.2 degrees. The systematic absences are
      consistent with the monoclinic space group C2 with one polypeptide chain in the
      asymmetric unit.

PMID- 8289298
TI  - Crystallization and preliminary crystallographic studies of Saccharomyces
      cerevisiae alcohol dehydrogenase I.
AB  - The cytoplasmic yeast alcohol dehydrogenase I crystallized at 5 degrees C as
      hexagonal plates or short columns in the presence of NAD+ and 2,2,2
      trifluoroethanol, in sodium N-tris(hydroxymethyl)methyl-3-aminopropanesulfonate
      buffer at pH 8.2 to 8.6, using polyethylene glycol 4000 as precipitant. X-ray
      diffraction data to 3.2 A resolution show that the crystals are hexagonal in
      space group P622 with unit cell dimensions a = b = 147.9 A, c = 69.1 A. There is
      one subunit of the tetrameric enzyme per asymmetric unit, giving a packing
      density of 2.9 A3/Da.

PMID- 8289299
TI  - Crystallization and X-ray studies of the DNA-binding domain of OmpR protein, a
      positive regulator involved in activation of osmoregulatory genes in Escherichia
      coli.
AB  - The OmpR protein of Escherichia coli is a positive regulator involved in the
      activation of expression of ompC and ompF genes encoding the major outer membrane
      protein OmpC and OmpF, respectively. The C-terminal half domain of OmpR (OmpR-C),
      which is responsible for DNA-binding, has been crystallized using the hanging
      drop vapour diffusion method. X-ray studies show that the crystals belong to the
      trigonal space group P3(1)21 (or P3(2)21) with a = b = 60.4 A, c = 58.8 A and
      gamma = 120 degrees. The asymmetric unit contains one molecule. The crystals
      diffract to at least 3 A resolution and are suitable for X-ray structure
      analysis.

PMID- 8289300
TI  - Crystallization and preliminary X-ray investigation of holotryptophanases from
      Escherichia coli and Proteus vulgaris.
AB  - Crystals of Proteus vulgaris holotryptophanase have been grown by the hanging
      drop technique using polyethylene glycol 4000 as precipitant in the presence of
      monovalent cations K+ or Cs+. Orthorhombic crystals (P2(1)2(1)2(1)) grown with
      Cs+ have unit cell parameters a = 115.0 A, b = 118.2 A and c = 153.7 A and
      diffract to 1.8 A. There are four subunits of the tetrameric molecule in the
      asymmetric unit. Native data have been collected to 2.5 A resolution. The 3.4 A
      data were collected from tetragonal crystals of Escherichia coli
      holotryptophanase grown under conditions described by Kawata et al. (1991). The
      molecular replacement solution for this crystal form has been found using
      tyrosine phenol-lyase coordinates. The correct enantiomorph is P4(3)2(1)2. There
      are two subunits in the asymmetric unit.

PMID- 8289301
TI  - Crystallization and preliminary X-ray diffraction studies of the soluble 14 kDa
      beta-galactoside-binding lectin from bovine heart.
AB  - The soluble 14 kDa beta-galactoside-binding lectin from bovine heart, a member of
      the S-type lectin family, has been crystallized in a form suitable for X-ray
      diffraction analysis. The crystals, in the absence of a saccharide ligand,
      diffract beyond 2.5 A resolution. They are obtained from polyethylene glycol 6000
      at pH 6.0. Crystals grow as monoclinic plates, space group P2(1), with cell
      dimensions: a = 35.47 A, b = 64.33 A, c = 58.78 A and beta = 91.7 degrees. The
      asymmetric unit contains two molecules related by a 2-fold non-crystallographic
      axis. Two lectin monomers in the asymmetric unit give a Vm of 2.4 A3/Da, i.e. a
      solvent content of approximately 50%. The complex of lectin with the saccharide
      ligand, N-acetyllactosamine, crystallizes in the space group P2(1)2(1)2 with cell
      dimensions: a = 63.55 A, b = 82.13 A and c = 62.39 A. Crystals of this complex
      diffract beyond 2.0 A resolution. Two complexes in the asymmetric unit lead to a
      Vm value of 2.8 A3/Da (57% solvent).

PMID- 8289302
TI  - Crystallization and preliminary X-ray studies of lipase B from Candida
      antarctica.
AB  - Lipase B from Candida antarctica has been crystallized in five different crystal
      forms. The space groups and cell dimensions have been determined by X-ray
      diffraction methods. Four of the crystal forms have been judged to be of good
      quality for further X-ray studies. The best crystals diffract to 1.7 Angstrom.

PMID- 8289303
TI  - Crystallization and preliminary crystallographic data of vitelline membrane outer
      layer protein I, VMO-I.
AB  - The vitelline membrane outer layer protein I (VMO-I), which is isolated from the
      vitelline membrane outer layer of hen's eggs, has been crystallized from an
      acetate buffer solution by the hanging-drop method. The crystals belong to the
      orthorhombic space group P2(1)2(1)2(1), with unit cell dimensions a = 62.42 A, b
      = 110.52 A, c = 44.15 A. There are two molecules (M(r) = 18,000) per asymmetric
      unit. The crystals diffract to at least 2.2 A Bragg spacings.

PMID- 8289304
TI  - Crystallization and preliminary X-ray diffraction analysis of the beta-chain of a
      T-cell antigen receptor.
AB  - A secreted form of the beta-chain of a T-cell receptor specific for a
      hemagglutinin peptide of influenza virus in the context of the major
      histocompatibility complex class II I-Ed molecule has been crystallized in a form
      suitable for X-ray diffraction analysis. The crystals are tetragonal, space group
      P4(1)2(1)2 (or P4(3)2(1)2), with cell dimensions a = b = 71.4 A, c = 312.9 A, and
      diffract to beyond 3.5 A resolution. The beta-chain appears to behave as a stable
      homodimer in solution.

PMID- 8289305
TI  - Conservation of a transcription antitermination mechanism in aminoacyl-tRNA
      synthetase and amino acid biosynthesis genes in gram-positive bacteria.
AB  - Most of the aminoacyl-tRNA synthetase genes identified to date in the Gram
      positive bacterium Bacillus subtilis have been found to be regulated by
      readthrough of a transcriptional terminator located in the mRNA leader region,
      upstream of the start of the coding sequence. All of these leader regions contain
      a series of conserved structural features, as well as a single codon displayed at
      a precise position within the structure, which has been shown for tyrS to be
      responsible for the specificity of the response to limitation for tyrosine. The
      structural features critical for transcription antitermination in Bacillus
      aminoacyl-tRNA synthetase genes were found in the B. subtilis ilv-leu
      biosynthetic operon, the Lactobacillus casei valS gene, the Corynebacterium
      glutaminicum argS gene, and three amino acid biosynthesis operons in
      Lactobacillus casei and Lactococcus lactis, suggesting that all of these genes
      are likely to be regulated by a similar antitermination mechanism. This
      regulatory system therefore appears to be widespread in Gram-positive bacteria.

PMID- 8289306
TI  - Determination of the nuclear magnetic resonance structure of the DNA-binding
      domain of the P22 c2 repressor (1 to 76) in solution and comparison with the DNA
      binding domain of the 434 repressor.
AB  - The solution structure of the N-terminal DNA-binding domain of the P22 c2
      repressor (residues 1 to 76) was determined by nuclear magnetic resonance (NMR)
      spectroscopy. The structure determination was based on nearly complete sequence
      specific resonance assignments for 1H, 13C and 15N, and tables of the chemical
      shifts for all three nuclei are included here. A group of 20 conformers was
      calculated from the NMR constraints using the program DIANA, and energy-minimized
      using an implementation of the AMBER force field in the program OPAL. The core of
      the protein formed by residues 5 to 68 is structurally well defined, with an
      average of 0.7 A for the root-mean-square deviations calculated for the backbone
      atoms of the individual conformers relative to the mean coordinates. The N
      terminal tetrapeptide segment and the C-terminal octapeptide segment are flexibly
      disordered. The molecular architecture includes five alpha-helical segments with
      residues 6 to 17, 21 to 28, 32 to 39, 47 to 57 and 61 to 65. The length and
      relative orientation of these helices are closely similar to the arrangement of
      corresponding regular secondary structures in the DNA-binding domain of the 434
      repressor, with the sole exception of the fourth helix, which is one turn longer
      at its amino-terminal end than the corresponding helix in the 434 repressor. This
      extension of the fourth helix implies that the DNA-binding mode of the P22 c2
      repressor must be somewhat different from that observed for the 434 repressor.
      Exact superposition of two P22 c2 repressor DNA-binding domains for best fit of
      corresponding polypeptide backbone atoms onto the two 434 repressor DNA-binding
      domains in the crystal structure of the 434 repressor-DNA complex would result in
      a model of the P22 c2 repressor-DNA complex which could not accommodate the
      fourth helices because of steric overlap.

PMID- 8289307
TI  - Lattice model simulations of polypeptide chain folding.
AB  - Simulated annealing methods are applied to simple cubic lattice C alpha models of
      eight small monomeric globular proteins and their transition from a random chain
      to a low energy compact state is examined. The lowest energy structures are
      compared to their crystal forms using coordinate distance deviations, dRMS and
      RMS, and by distance contact maps. Analysis of the transition region indicates
      that, for this model, collapse begins with a rapid decline in radius of gyration
      followed continuously by chain repackings that lead to progressively lower values
      of chain energy. Chain repackings represent a highly cooperative interplay
      between the formation of local and non-local interactions. The components of this
      transition are characterized by rapid relaxation of shorter chain segments to
      form local contacts and slower relaxations of longer chain segments to form non
      local contacts. Final structures obtained with this procedure contain many of the
      gross topologies of their native structures.

PMID- 8289308
TI  - Conformational analysis of a 139 base-pair DNA fragment containing a single
      stranded break and its interaction with human poly(ADP-ribose) polymerase.
AB  - The conformational changes induced by the introduction of a central and unique
      single-stranded break in a 139 base-pair DNA duplex have been analysed by means
      of polyacrylamide gel electrophoresis, HPLC and dark-field electron microscopy.
      Compared to the control DNA, the disruption of the covalent sugar-phosphate
      backbone induces a retardation detected both by gel electrophoresis and anion
      exchange based HPLC. Electron microscopic visualization of the DNA molecules
      reveals that most of them present a central fracture at the position of the nick.
      Measures of the angle at the apex were very well fitted by a simple model of
      isotropic flexible junction assuming spatial Hooke's law and simple basic
      Boltzmann statistics. This amounts to using a folded Gaussian distribution. The
      fit yields an angle equilibrium value phi 0 = 122 degrees for the nicked
      fragment. The angle distribution could also result from an equilibrium between
      two forms of the molecule with isotropic flexibility at the nicked site: a
      stacked and a very flexible unstacked form. The majority of bound poly(ADP
      ribose) polymerase, a zinc-finger enzyme involved in DNA break detection, was
      localized at the apex of the V-shaped DNA duplex, with an accentuation of its
      general V-shaped conformation (phi 0 = 102 degrees).

PMID- 8289309
TI  - 1H nuclear magnetic resonance studies of hen lysozyme-N-acetylglucosamine
      oligosaccharide complexes in solution. Application of chemical shifts for the
      comparison of conformational changes in solution and in the crystal.
AB  - Two-dimensional 1H nuclear magnetic resonance spectroscopy has been used to
      examine the complexes formed in solution between hen egg-white lysozyme and N
      acetylglucosamine (GlcNAc) oligosaccharides. Changes in chemical shift have been
      measured for resonances of the majority of residues of lysozyme on binding the
      monomer, dimer and trimer of GlcNAc. The three inhibitors induce very similar
      changes in chemical shift, and these increase slightly with the length of the
      oligosaccharide. The largest changes are confined principally to the vicinity of
      site C in the active site cleft of the enzyme. These changes in chemical shift
      have been compared with differences in the ring current chemical shifts
      calculated from the crystal structures of unbound and GlcNAc3 bound lysozyme.
      This comparison suggests that the major conformational changes of residues in the
      vicinity of site C of the enzyme, that are caused by the binding of GlcNAc3,
      observed in the diffraction studies are at least consistent with the changes that
      occur in solution. Small changes in chemical shift are observed in the enzyme in
      regions remote from the active site, which indicate that the effects of inhibitor
      binding are felt throughout the enzyme. These changes in chemical shift correlate
      to a lesser extent than those near site C with the changes in chemical shift
      predicted from changes in conformation observed in the crystal structures. The
      results illustrate that chemical shifts are useful in assessing the significance
      of small conformational changes in proteins, although the usefulness of this
      approach will be limited by the resolution of the crystallographic structures, as
      well as the uncertainties in the origins of the chemical shift. Although
      conformational changes in site C account for many of the changes in the NMR
      spectrum of lysozyme, evidence is, however, presented for multiple binding sites
      for the GlcNAc oligosaccharides in solution, perhaps involving partial occupancy
      of site D.

PMID- 8289310
TI  - Catalytic antibody model and mutagenesis implicate arginine in transition-state
      stabilization.
AB  - To probe the mechanism of the catalytic antibody NPN43C9, we have constructed a
      three-dimensional model of the NPN43C9 variable region using our antibody
      structural database (ASD), which takes maximal advantage of immunoglobulin
      sequence and structural information. The ASD contains separately superimposed
      variable light and variable heavy chains, which reveal not only conserved
      backbone structure, but also structurally conserved side-chain conformations. The
      NPN43C9 model revealed that the guanidinium group of light chain Arg L96 was
      positioned at the bottom of the antigen-binding site and formed a salt bridge
      with the antigen's phosphonamidate group, which mimics the negatively charged,
      tetrahedral transition states in the hydrolysis reaction. Thus, the model
      predicts both binding and catalytic functions for Arg L96, which previously had
      not been implicated in either. First, Arg L96 should enhance antigen binding by
      electrostatically complementing the negative charge of the antigen, which is
      buried upon complex formation. Second, Arg L96 should promote catalysis by
      electrostatically stabilizing the negatively charged transition states formed
      during catalysis. These hypotheses were tested experimentally by design and
      characterization of the R-L96-Q mutant, in which Arg L96 was replaced with Gln by
      site-directed mutagenesis. As predicted, antigen binding in the R-L96-Q mutant
      was decreased relative to that in the parent NPN43C9 antibody, but binding of
      antigen fragments lacking the phosphonamidate group was retained. In addition,
      the R-L96-Q mutant had no detectable esterase activity. Thus, the computational
      model and experimental results together suggest a mechanism by which the
      catalytic antibody NPN43C9 stabilizes high-energy transition states during
      catalysis.

PMID- 8289311
TI  - Interactions of plasminogen with polymerizing fibrin and its derivatives,
      monitored with a photoaffinity cross-linker and electron microscopy.
AB  - Localization of the plasminogen binding sites on fibrin has been difficult since
      these interactions occur on polymerizing fibrin, and studies with fragments can
      be misleading because of multiple carboxyl-terminal lysines that may bind to
      plasminogen. A hetero-functional photoaffinity cross-linker was used to study
      these interactions. Following attachment of the cross-linker to plasminogen in
      the dark, a clot was formed by addition of fibrinogen or fragment X and thrombin,
      and then the plasminogen was cross-linked to adjacent parts of fibrin by exposure
      to light. There was more Glu1-plasminogen bound to fibrin than to fibrinogen and
      more to fragment X polymer than to fibrin. Electron microscopy of rotary shadowed
      individual molecules reveals that Glu1-plasminogen appears to be more compact
      than Lys78-plasminogen or Glu1-plasminogen with 6-aminohexanoic acid. Cross
      linked complexes from the dissolved clot observed by electron microscopy reveal
      plasminogen bound to the end of fibrin or bridging the ends of two fibrin
      molecules; larger complexes were also observed. Analysis of changes in the
      appearance of negatively contrasted fibers with plasminogen bound also indicates
      the probable locations of binding sites, yielding results consistent with the
      cross-linking studies. The photoaffinity probe was also used to study
      interactions between plasminogen and fibrin or its derivatives in the course of
      tissue plasminogen activator-mediated fibrinolysis. Samples cross-linked at
      various times indicate that complexes with fragment X are particularly dominant
      during the rapid phase of plasminogen activation. In conclusion, these studies
      indicate that plasminogen binds to the pocket at the end-to-end junction between
      two fibrin or fragment X molecules in the protofibril; from this position, it can
      reach all of the sites that are cleaved during fibrinolysis.

PMID- 8289312
TI  - Preliminary analysis of multiple crystal forms of the bovine cyclophilin
      cyclosporin A complex.
AB  - The immunosuppressant cyclosporin-A (CsA) has been crystallized in complex with
      the bovine form of its major receptor protein cyclophilin (CyP) in three
      different forms by the hanging-drop vapor diffusion method. A hexagonal crystal
      form (P6(1)22 or P6(5)22; a = b = 110 A, c = 440 A) diffracts to 4 A resolution.
      Orthorhombic (P2(1)2(1)2(1) or P2(1)2(1)2; a = 154.3 A, b = 163.3 A, c = 94.7 A),
      and monoclinic (P2(1); a = 70.0 A, b = 162.5 A, c = 94.7, beta = 100.0 degrees)
      forms diffract to 2.2 A resolution. Self-rotation function analysis of the
      orthorhombic and monoclinic forms shows 52 point group local symmetry for both. A
      previously reported tetragonal crystal form of the complex also shares this local
      symmetry, suggesting that the observed motif may pre-exist in solution.

PMID- 8289313
TI  - Crystallization and a preliminary X-ray diffraction study of macrophage migration
      inhibitory factor from human lymphocytes.
AB  - Two crystal forms of the macrophage migration inhibitory factor (MIF) from human
      lymphocytes have been obtained by the hanging drop method of vapor diffusion from
      ammonium sulfate solution. A trigonal crystal form belongs to the space group
      P3(1)21 (P3(2)21), with unit cell dimensions of a = b = 96.4 A and c = 105.5 A.
      Assuming that the asymmetric unit contains two or three dimers, the Vm value is
      calculated as 2.9 or 1.9, respectively. A second crystal form is orthorhombic,
      space group P2(1)2(1)2(1) with unit cell dimensions a = 68.4 A, b = 68.8 A and c
      = 86.8 A. The Vm value is 2.1 for two dimers in the asymmetric unit. Both
      crystals diffract to at least 1.9 A and are suitable for X-ray crystallographic
      structure determination at a high resolution.

PMID- 8289314
TI  - Preliminary crystallographic studies on human complement pro-factor D.
AB  - The recombinant zymogen of the human complement protein factor D has been
      crystallized. Crystals were grown by vapor diffusion using polyethylene glycol
      6000 as precipitant. Two crystal forms obtained at pH 5.4 belong to space group
      P2(1). The crystals grow to dimensions of 0.6 mm x 0.3 mm x 0.3 mm in three days,
      are stable in the X-ray beam, and diffract to 2.4 A.

PMID- 8289315
TI  - Preliminary X-ray analysis of a truncated form of recombinant fructose-2,6
      bisphosphatase.
AB  - The bisphosphatase domain of rat liver 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase and a C-terminal 30 amino acid truncated form were expressed in
      high yield in Escherichia coli and purified to homogeneity. The separately
      expressed bisphosphatase domain and its C-terminal truncated form had kinetic
      properties similar to the bisphosphatase of the intact bifunctional enzyme, but
      their turnover numbers were fourfold higher. The truncated enzyme crystallized in
      space group P1 with two molecules per asymmetric unit. The determined cell
      dimensions are: a = 41.9 A, b = 43.5 A, c = 57.6 A, alpha = 95.2 degrees, beta =
      99.3 degrees, and gamma = 106.2 degrees. These crystals diffract to 2.0 A
      resolution when exposed to synchrotron radiation and are suitable for
      crystallographic structure analysis.

PMID- 8289316
TI  - A new crystal form of abrin-a from the seeds of Abrus precatorius.
AB  - A new crystal form of abrin-a from the seeds of Abrus precatorius has been
      obtained by vapor diffusion method. The abrin-a crystals belong to monoclinic
      space group P2(1) with cell dimensions a = 84.58 A, b = 73.07 A, c = 48.23 A,
      beta = 96.20 degrees. An asymmetric unit contains one protein molecule of
      molecular weight 65 kDa and has a solvent content of approximately 46%.

PMID- 8289317
TI  - Crystallization and preliminary X-ray investigation of a recombinant outer
      membrane protein from Neisseria meningitidis.
AB  - A protein constituent of the outer membrane from Neisseria meningitidis
      (hereafter called P64K) has been crystallized using the hanging drop technique.
      Crystals are tetragonal with unit cell dimensions a = b = 136.84 A and c = 78.44
      A, compatible with a single monomer of 64 kDa in the asymmetric unit. When
      exposed to high intensity synchrotron radiation, these crystals diffract X-rays
      to at least 2.9 A resolution, indicating that a high resolution structure
      analysis is feasible.

PMID- 8289318
TI  - Crystallization and preliminary X-ray analysis of the superoxide dismutase from
      Mycobacterium tuberculosis.
AB  - The iron-dependent superoxide dismutase from Mycobacterium tuberculosis has been
      crystallized by the hanging drop method. The crystals belong to the P2(1) space
      group and have unit cell dimensions of a = 68.5 A, b = 85.6 A, c = 66.5 A, beta =
      99.8 degrees. There are four molecules per asymmetric unit which, from analysis
      of data to 2.5 A, appear to be related by non-crystallographic 222 symmetry.

PMID- 8289319
TI  - Crystallization of a DNA and N-acetylserine binding fragment (residues 1 to 233)
      of Klebsiella aerogenes CysB protein, a member of the LysR family.
AB  - CysB protein is a positive regulator of transcription of genes involved in
      cysteine biosynthesis in bacteria and a member of the LysR family of DNA binding
      proteins. A 233-residue N-terminal chymotryptic fragment of the protein, with DNA
      and N-acetylserine binding activity, has been crystallized in the presence of
      monomethyl-polyethylene glycol 750. The crystals diffract to 2.5 A (1 A = 0.1 nm)
      spacing on a rotating copper anode X-ray source and to 2.1 A spacing using
      synchrotron radiation and are suitable for structural studies. The space group is
      P2(1)2(1)2 with unit cell dimensions of a = 68.8 A, b = 109.9 A and c = 33.5 A.
      On the assumption that the asymmetric unit comprises one monomer, the crystals
      have a solvent content of approximately 50%.

PMID- 8289320
TI  - Heterocyst-forming filamentous cyanobacteria encode proteins that resemble
      eukaryotic RNA-binding proteins of the RNP family.
AB  - Heterocyst-forming cyanobacteria have multiple genes encoding proteins that are
      similar to the RNP family of eukaryotic RNA-binding proteins. Three genes from
      two strains of cyanobacteria (Anabaena and Chlorogloeopsis) have been sequenced.
      All three putative gene products contain a single RNA Recognition Motif (RRM)
      that includes the highly conserved RNP1 and RNP2 regions and all three have an
      auxiliary motif consisting either of a short glycine-rich carboxy-terminal tail
      or a carboxy-terminal tail rich in both asparagine and glycine. RNA-binding
      protein genes are abundant in heterocyst-forming filamentous cyanobacteria but
      are not abundant in non-heterocyst-forming filamentous or unicellular
      cyanobacteria suggesting that the cyanobacterial proteins may play a role in gene
      expression during heterocyst differentiation. The cyanobacterial gene products
      share a significant degree of similarity with the RNP family of RNA-binding
      proteins which includes snRNP proteins, hnRNP proteins, nucleolins, as well as
      some regulatory proteins and some plant chloroplast proteins. Although the exact
      function of the cyanobacterial gene products is not yet known, their similarity
      to eukaryotic proteins suggests that they may play a role in RNA processing and
      metabolism. Finally, the presence of these genes in cyanobacteria has
      implications for the evolution of RNA binding proteins and RNA processing.

PMID- 8289321
TI  - Unusual kinetics of uracil formation in single and double-stranded DNA by
      deamination of cytosine in cyclobutane pyrimidine dimers.
AB  - Mutagenesis studies have indicated that the deamination of cytosine in UV-induced
      cyclobutane pyrimidine dimers is a key part of an error-free process that can
      account for most of the C-->T base specificity that frequently characterizes UV
      induced mutagenesis. The kinetics of deamination, as inferred from the mutagenic
      effect of delayed photoreactivation, is remarkable in its resemblance to a step
      function. To study the kinetics from a different point of view, we used an
      enzymatic approach combining photolyase and uracil-N-glycosylase treatment to
      detect the formation of uracil in UV-irradiated single or double-stranded
      infectious DNA of phage S13. Formation of abasic sites by removal of uracil was
      inferred from loss of infectivity. It is concluded that no uracil appeared at 37
      degrees C within 20 minutes (single-stranded DNA) or 40 minutes (double-stranded
      DNA) after irradiation, but following those latent periods, most of the uracil
      residues rapidly appeared within a brief 14 minute period centered at 29 minutes
      (single-stranded DNA) and 55 minutes (double-stranded DNA) after irradiation. The
      timing appears to fully confirm the previous evidence that dimer cytosines in DNA
      deaminate with step-function-like kinetics. Furthermore, the appearance of uracil
      was shown to be dependent on the UV-induction of cyclobutane dimers containing
      cytosine.

PMID- 8289322
TI  - The twist, writhe and overall shape of supercoiled DNA change during counterion
      induced transition from a loosely to a tightly interwound superhelix. Possible
      implications for DNA structure in vivo.
AB  - A cryo-electron microscopy study of supercoiled DNA molecules freely suspended in
      cryo-vitrified buffer was combined with Monte Carlo simulations and gel
      electrophoretic analysis to investigate the role of intersegmental electrostatic
      repulsion in determining the shape of supercoiled DNA molecules. It is
      demonstrated here that a decrease of DNA-DNA repulsion by increasing
      concentrations of counterions causes a higher fraction of the linking number
      deficit to be partitioned into writhe. When counterions reach concentrations
      likely to be present under in vivo conditions, naturally supercoiled plasmids
      adopt a tightly interwound conformation. In these tightly supercoiled DNA
      molecules the opposing segments of interwound superhelix seem to directly contact
      each other. This form of supercoiling, where two DNA helices interact laterally,
      may represent an important functional state of DNA. In the particular case of
      supercoiled minicircles (178 bp) the delta Lk = -2 topoisomers undergo a sharp
      structural transition from almost planar circles in low salt buffers to strongly
      writhed "figure-eight" conformations in buffers containing neutralizing
      concentrations of counterions. Possible implications of this observed structural
      transition in DNA are discussed.

PMID- 8289323
TI  - Specificity of DnaK-peptide binding.
AB  - The sequence specificity of DnaK substrate binding has been studied using a
      peptide display library. Based on the amino acid patterns that appeared in this
      selection, short peptides were synthesized for direct measurements of DnaK
      affinity. The results show that peptides enriched in internal hydrophobic
      residues are preferential DnaK substrates, and negatively charged peptides have
      poor affinity. The isolated C-terminal domain of DnaK binds peptides. Peptide
      dissociation studies indicate that bound peptides are released from the C
      terminal fragment and from DnaK at identical rates. ATP stimulates peptide
      dissociation from DnaK but not from the C-terminal fragment.

PMID- 8289324
TI  - DNA sequence organization in chromatosomes.
AB  - The chromatosome is a structural unit of chromatin which contains a histone
      octamer and one linker histone molecule (H5, H1a or H1b in chicken erythrocytes)
      bound to 168 bp of DNA (= core particle DNA extended by 22 bp). We have cloned
      and sequenced 280 DNA fragments of 163 to 173 bp in length isolated from chicken
      erythrocyte chromatosomes. We have analysed both this set and a subset of 171
      clones whose lengths varied between 166 and 170 bp. The periodic modulation of
      the frequency of occurrence of trinucleotide sequences is neither as regular nor
      as pronounced for core particle DNA, even for the trinucleotide ApApA/TpTpT.
      Nevertheless for this trinucleotide the congruence of the preferential and
      avoided locations between the two sets is remarkable. We conclude that the
      rotational positioning of the DNA bound to the histone octamer is essentially the
      same in chromatosomes and nucleosome core particles. This conclusion is confirmed
      by Fourier analysis, which shows that within the central 145 bp the average
      rotational periods of about 10-20 bp and phases are very similar to those in core
      DNA. However the amplitude of the modulations is less, indicating that the
      binding of the linker histone can overcome to a certain extent the sequence
      dependent bending preferences of DNA. Although the rotational signals are largely
      conserved the sequence organization of the chromatosomal DNA differs in
      significant ways from that of core particle DNA. The major difference is the
      preferential occurrence of short G+C-rich instead of A+T-rich sequences at the
      midpoint of the binding site. The second apparent difference is the exclusion of
      short oligo(dA).(dT) tracts from positions about 40 to 43 bp on either side of
      the midpoint in chromatosomal, but not in core particle DNA. Finally, we show
      that particular base-steps are preferentially enriched close to the termini of
      chromatosomal DNA and propose that these sequences may constitute one of the two
      DNA binding sites for the bivalent globular domain of histones H5 or H1. The
      implications for the positioning of GH5 relative to the path of the DNA
      superhelix are discussed.

PMID- 8289325
TI  - On the location of linker DNA in the chromatin fiber. Studies with immobilized
      and soluble micrococcal nuclease.
AB  - The structure of chicken erythrocyte chromatin fibers has been probed using
      micrococcal nuclease, both membrane-immobilized and free in solution. Under the
      extremely mild digestion conditions used, the linker DNA is almost completely
      protected against digestion with either immobilized or free enzyme in the 30 nm
      fibers, whereas it is readily accessible in the more extended structures. Control
      experiments with glutaraldehyde-fixed chromatin fibers gave essentially the same
      results. Experiments with fibers of intermediate degree of condensation revealed
      a direct relationship between the degree of compaction and the resistance of
      linker DNA to digestion. Our results favor models in which access to the linkers
      is limited by local steric hindrance due to the high compaction, rather than by
      internalization in the center of the fibers.

PMID- 8289326
TI  - Expression of mitochondrial genes in the germinating conidia of Neurospora
      crassa.
AB  - The germinating asexual spores (conidia) of Neurospora crassa were employed to
      study steps in the accumulation of transcripts of groups of mitochondrial genes,
      including those for peptide subunits of cytochrome c oxidase (CO), ATPase (ATP),
      and apocytochrome b (COB). Physically clustered groups of genes were expressed as
      cohorts: transcripts of the ATP8-ATP6-mtATP9-CO2 genes were almost undetectable
      in the dormant spores, and they accumulated rapidly as a group immediately after
      spore activation. Transcripts of COB and the adjacent CO1 were abundant in the
      dormant spores, and the dormant and germinating spores contained size forms of
      the COB transcripts that were not evident in vegetative cells. Polyribosomes were
      prepared from mitochondrial lysates, and the polyribosomal RNA was probed to
      identify the mRNAs of specific genes; in several instances polycistronic mRNAs
      were present in the polyribosomes as were the smaller end-products of the
      inferred transcript processing pathways. The expression of the physically
      dispersed genes for subunit peptides of cytochrome c oxidase appears to be
      regulated to the level of translation; these transcripts are accumulated in the
      total mitochondrial RNA with sharply different kinetics, but they appeared in the
      polyribosomes uniformly, their appearance correlating with the uniform synthesis
      of the subunit peptides. Transcripts for a previously reported non-functional
      mitochondrial gene, homologous to the functional nuclear gene for ATPase subunit
      9, were found in the germinating spores, but were not detected in vegetative
      cells. These mtATP9 transcripts were also present in the polyribosomes and were
      apparently translated into a protein in vivo whose synthesis was insensitive to
      cycloheximide and detectable with an anti-ATP9 subunit antibody. Transcripts for
      two nuclear genes for mitochondrially localized proteins, ATP9 and CO5, were
      accumulated in unison and especially rapidly during spore germination.

PMID- 8289327
TI  - Mapping the functional domains of bacteriophage lambda integrase protein.
AB  - Bacteriophage lambda encodes a site-specific recombination system that promotes
      the movement of the phage genome into and out of the host bacterial chromosome.
      The phage-encoded integrase (Int) is composed of 356 amino acid residues and
      carries out the required strand exchanges by means of a type I topoisomerase
      activity. Int also contains two distinct DNA-binding domains that interact with
      two different, specific sequences (arm-type and core-type sites) on DNA. In order
      to help understand the mechanism of site-specific recombination, we have used a
      genetic approach to isolate mutants defective in different steps in the
      recombination reaction. We developed a genetic screen for Int mutants that are
      defective in catalyzing excisive recombination in vivo. These mutants were
      screened for proficiency in binding to the P'123 arm-type sites using the
      bacteriophage P22 challenge-phage assays. In all, 78 such mutants were isolated
      and the mutational changes mapped and sequenced. These mutants have been further
      characterized (1) for their ability to bind the P'1 and P'123 arm-type sites and
      for their ability to form the attL complex in vivo, (2) for negative dominance in
      vitro, (3) for the presence of type I topoisomerase activity, and (4) for the
      ability to resolve artificially constructed recombination intermediates. We found
      that (1) residues in a stretch of 88 amino acids in the middle of the protein may
      be involved in Int-Int interactions, (2) a region around Arg212 is involved in
      the catalytic site, (3) residues near the carboxyl terminus play a role in
      enhancing Int binding to its arm-type sites, possibly by interacting with the
      small amino-terminal region that has been shown to be responsible for specific
      recognition of the arm-type sites, and (4) residues at the very carboxyl end of
      the protein may be involved in modulating the cleavage or religation activities
      of the Int protein.

PMID- 8289328
TI  - Bona fide prediction of aspects of protein conformation. Assigning interior and
      surface residues from patterns of variation and conservation in homologous
      protein sequences.
AB  - Heuristics have been developed for analyzing patterns of conservation and
      variation within a set of aligned homologous protein sequences for the purpose of
      assigning amino acids whose side-chains lie on the surface and inside the folded
      structure of a protein. These were used in several recent bona fide predictions
      of the secondary structure of proteins from sequence data, made and published
      before crystallographic information became available. Heuristics based on
      concurrent hydrophilic variation identify positions that lie on the surface.
      Heuristics based on concurrent hydrophobic conservation and variation identify
      positions lying in the interior. These heuristics are described here in detail
      and their performance evaluated when applied to seven protein families with known
      three-dimensional structures. The performance of individual heuristics is shown
      to depend on the nature of the multiple alignment within the protein family, and
      a strategy is presented for obtaining surface and interior assignments useful for
      predicting secondary structure.

PMID- 8289329
TI  - Biased probability Monte Carlo conformational searches and electrostatic
      calculations for peptides and proteins.
AB  - Two major components are required for a successful prediction of the three
      dimensional structure of peptides and proteins: an efficient global optimization
      procedure which is capable of finding an appropriate local minimum for the
      strongly anisotropic function of hundreds of variables, and a set of free energy
      components for a protein molecule in solution which are computationally
      inexpensive enough to be used in the search procedure, yet sufficiently accurate
      to ensure the uniqueness of the native conformation. We here found an efficient
      way to make a random step in a Monte Carlo procedure given knowledge of the
      energy or statistical properties of conformational subspaces (e.g. phi-psi zones
      or side-chain torsion angles). This biased probability Monte Carlo (BPMC)
      procedure randomly selects the subspace first, then makes a step to a new random
      position independent of the previous position, but according to the predefined
      continuous probability distribution. The random step is followed by a local
      minimization in torsion angle space. The positions, sizes and preferences for
      high-probability zones on phi-psi maps and chi-angle maps were calculated for
      different residue types from the representative set of 191 and 161 protein 3D
      structures, respectively. A fast and precise method to evaluate the electrostatic
      energy of a protein in solution is developed and combined with the BPMC
      procedure. The method is based on the modified spherical image charge
      approximation, efficiently projected onto a molecule of arbitrary shape.
      Comparison with the finite-difference solutions of the Poisson-Boltzmann equation
      shows high accuracy for our approach. The BPMC procedure is applied successfully
      to the structure prediction of 12- and 16-residue synthetic peptides and the
      determination of protein structure from NMR data, with the immunoglobulin binding
      domain of streptococcal protein G as an example. The BPMC runs display much
      better convergence properties than the non-biased simulations. The advantage of a
      true global optimization procedure for NMR structure determination is its ability
      to cope with local minima originating from data errors and ambiguities in NMR
      data.

PMID- 8289330
TI  - Transcription factor PRDII-BF1 activates human immunodeficiency virus type 1 gene
      expression.
AB  - Gene expression of human immunodeficiency virus (HIV) is modulated by both
      cellular transcription factors, which bind to cis-acting regulatory elements in
      the HIV-1 long terminal repeat (LTR) and the viral transactivator, tat. The
      enhancer element in the HIV-1 LTR which extends from -103 to -82 is critical for
      gene expression. This region contains two identical 10-bp direct repeats which
      serve as binding sites for members of the NF-kappa B family of transcription
      factors. However, several other cellular transcription factors, including a group
      of zinc finger DNA-binding proteins, also bind to NF-kappa B and related motifs.
      A member of this family of transcription factors, designated PRDII-BF1 or MBP-1,
      is a 300-kDa cellular protein which contains two widely separated zinc finger DNA
      binding domains. Each of these binding domains is capable of binding to NF-kappa
      B or related recognition motifs. Since no functional role for this protein has
      been demonstrated in the regulation of viral and cellular promoters, we began
      studies to determine whether PRDII-BF1 could modulate HIV-1 gene expression.
      DNase I footprinting of the HIV-1 LTR indicated that PRDII-BF1 bound to both NF
      kappa B and TAR transactivation response DNA elements. Both in vitro translation
      and vaccinia virus expression of PRDII-BF1 cDNA resulted in the synthesis of the
      full-length 300-kDa PRDII-BF1 protein. Transfection experiments, using both
      eucaryotic expression vectors and antisense constructs, indicated that PRDII-BF1
      activated HIV-1 gene expression in both the presence and absence of tat. These
      results are consistent with a role for PRDII-BF1 in activating HIV-1 gene
      expression.

PMID- 8289331
TI  - Association between the p170 form of human topoisomerase II and progeny viral DNA
      in cells infected with herpes simplex virus type 1.
AB  - Endogenous host topoisomerase II acts upon herpes simplex virus type 1 (HSV-1)
      DNA in infected cells (S.N. Ebert, S.S. Shtrom, and M.T. Muller, J. Virol.
      56:4059-4066, 1990), and cleavage is directed exclusively at progeny viral DNA
      while parental DNA is resistant. To evaluate the possibility that HSV-1 induces
      topoisomerase II activity which could account for the preferential cleavage of
      progeny viral DNA, we assessed topoisomerase II cleavage activity on cellular and
      viral DNA substrates before and after the initiation of viral DNA replication. We
      show that cleavage of a host gene in mock-infected cells was similar to that
      observed in HSV-1-infected cells, regardless of whether viral DNA replication had
      occurred. In addition, quantitative measurements revealed comparable amounts of
      topoisomerase II activity in infected and mock-infected cells; thus, HSV-1
      neither induces nor encodes its own type II topoisomerase and cleavages in vivo
      are due to a preexisting host topoisomerase. Human cells contain two isozymes of
      topoisomerase II (p170 and p180), encoded by separate genes. Through the use of
      isozyme-specific antibodies, we demonstrate that only p170 was found to be cross
      linked to HSV-1 DNA even though both forms were present at nearly constant levels
      in HSV-1-infected cells. Immunofluorescence revealed that by 6 h postinfection,
      p170 becomes redistributed and localized to sites of active viral DNA synthesis.
      The data suggest that p170 gains preferential access to replicated viral DNA
      molecules, which explains why topoisomerase II activity is concentrated on
      progeny DNA.

PMID- 8289332
TI  - Transcriptional mapping of the 3' end of the bovine syncytial virus genome.
AB  - The bovine syncytial virus, a member of the retroviral subfamily Spumavirinae,
      causes a persistent, asymptomatic infection in cattle. Nucleotide sequence
      analysis of the viral genome revealed two overlapping reading frames in the 3'
      region, traditionally occupied by accessory-function genes in other complex
      retroviruses. In order to analyze the transcripts from the accessory-gene region,
      we designed oligonucleotide primers complementary to sequences within the 5' and
      3' long terminal repeats (LTRs) for use with the PCR. Southern blot analysis of
      amplification products revealed eight major cDNA bands. Eleven distinct cDNA
      clones were subsequently isolated and characterized. The initial splice donor in
      each clone is located 49 bp downstream from the mRNA cap site in the 5' LTR. The
      primary splice acceptor site was located 17 bp upstream from the proximal 3' open
      reading frame known as BF-ORF1. A second major splice acceptor was localized to a
      region upstream of the second open reading frame, BF-ORF2. Clones were identified
      which spliced directly to each of these sites. Additional splice donor and
      acceptor sites within BF-ORF1 and BF-ORF2 and the 3' LTR were variously used to
      generate a complex array of multiply spliced transcripts. Each of these
      transcripts remained in frame and coded for a potential protein product.

PMID- 8289333
TI  - Human cytomegalovirus DNA replicates after early circularization by concatemer
      formation, and inversion occurs within the concatemer.
AB  - To determine the replicative mechanism for human cytomegalovirus (HCMV) DNA,
      field inversion gel electrophoresis was used to separate HCMV replicative DNAs
      during lytic infection. Unit-length circular HCMV genomes lacking terminal
      restriction fragments were detected starting 4 h after infection even when cells
      were treated with aphidicolin, phosphonoacetic acid, or cycloheximide. Viral DNA
      synthesis began 24 h after infection and produced large amounts of high-molecular
      weight replicative DNA that was a precursor of progeny genomes. Replicative DNA
      contained rare terminal restriction fragments, and long-arm termini were much
      less frequent than short-arm termini. Replicative DNA was not composed of unit
      length circles because low-dose gamma irradiation of replicative DNA generated
      numerous random high-molecular-weight fragments rather than unit-length
      molecules. PacI digestion of replicative DNA from a recombinant HCMV with two
      closely spaced PacI sites revealed that replicative DNA is concatemeric and
      genome segment inversion occurs after concatemer synthesis. These results show
      that after circularization of the parental genome, DNA synthesis produces
      concatemers and genomic inversion occurs within concatemeric DNA. The results
      further suggest that concatemers acquire genomic termini during the
      cleavage/packaging process which preferentially inserts short-arm termini into
      empty capsids, causing a predominance of short-arm termini on the concatemer.

PMID- 8289334
TI  - Expression of the hepatitis delta virus large and small antigens in transgenic
      mice.
AB  - Simultaneous infection with hepatitis delta virus (HDV) and hepatitis B virus
      (HBV) in humans is often associated with severe viral liver disease including
      fulminant hepatitis. Since HBV is thought to be noncytopathic to the hepatocyte,
      the enhanced disease severity observed during dual infection has been attributed
      to either simultaneous immune responses against the two viruses or direct
      cytotoxic effects of HDV products on the hepatocyte or both. To examine these
      alternate possibilities, we produced transgenic mice that express the small and
      large delta antigens (HDAg) in hepatocyte nuclei at levels equal to those
      observed during natural HDV infection. No biological or histopathological
      evidence of liver disease was detectable during 18 months of observation,
      suggesting that neither the large nor small form of HDAg is directly cytopathic
      to the hepatocyte in vivo.

PMID- 8289335
TI  - The carbocyclic analog of 2'-deoxyguanosine induces a prolonged inhibition of
      duck hepatitis B virus DNA synthesis in primary hepatocyte cultures and in the
      liver.
AB  - The carbocyclic analog of 2'-deoxyguanosine (2'-CDG) is a strong inhibitor of
      hepatitis B virus (HBV) DNA synthesis in HepG2 cells (P.M. Price, R. Banerjee,
      and G. Acs, Proc. Natl. Acad. USA 86:8543-8544, 1989). We now report that 2'-CDG
      inhibited duck hepatitis B virus (DHBV) DNA synthesis in primary cultures of duck
      hepatocytes and in experimentally infected ducks. Like foscarnet (phosphonoformic
      acid [PFA]) and 2'-,3'-dideoxycytidine (ddC), 2'-CDG blocked viral DNA
      replication in primary hepatocyte cultures when present during an infection but
      failed to inhibit the DNA repair reaction that occurs during the initiation of
      infection to convert virion relaxed circular DNA to covalently closed circular
      DNA, the template for viral mRNA transcription. Moreover, as for PFA and ddC,
      viral RNA synthesis was detected when infection was initiated in the presence 2'
      CDG. In another respect, however, 2'-CDG exhibited antiviral activity unlike that
      of ddC or PFA: a single 1-day treatment of hepatocytes with 2'-CDG blocked
      initiation of viral DNA synthesis for at least 8 days, irrespective of whether
      DHBV infection was carried out at the time of drug treatment or several days
      later. Furthermore, orally administered 2'-CDG was long-acting against DHBV in
      experimentally infected ducklings. Virus replication was delayed by up to 4 days
      in ducklings infected after administration of 2'-CDG. These observations of long
      lasting efficacy in vitro and in vivo even after oral administration suggest that
      this inhibitor or a nucleoside with similar pharmacological properties may be
      ideal for reducing virus replication in patients with chronic HBV infection.

PMID- 8289336
TI  - In vitro characterization of an internal ribosomal entry site (IRES) present
      within the 5' nontranslated region of hepatitis A virus RNA: comparison with the
      IRES of encephalomyocarditis virus.
AB  - The lengthy 5' nontranslated region (5'NTR) of hepatitis A virus (HAV) forms a
      highly ordered secondary structure, which has been suggested to play an important
      role in controlling viral translation by allowing for translation initiation by
      internal ribosome entry. To test this hypothesis, synthetic bicistronic RNAs,
      with all or part of the HAV 5'NTR in the intercistronic space, were translated in
      rabbit reticulocyte lysates. In the presence of an upstream cistron designed to
      block ribosomal scanning, the HAV 5'NTR was capable of directing the internal
      initiation of translation, confirming the presence of an internal ribosome entry
      site (IRES). Analysis of various deletion mutants demonstrated that the 5' border
      of the IRES is located between nucleotides 151 and 257, while the 3' border
      extends to the 3' end of the 5'NTR, between nucleotide 695 and the first
      initiation codon at 735. Except for a segment between bases 638 and 694, deletion
      of stem-loop structures between bases 151 and the 3' end of the 5'NTR inhibited
      or abolished translation. The addition of a 5' cap structure (m7GpppN) to
      monocistronic or bicistronic transcripts decreased the translation of a reporter
      gene downstream of the HAV 5'NTR but enhanced translation of the upstream cistron
      in bicistronic transcripts. This finding indicates that a 5' cap structure is
      inhibitory to HAV IRES-directed translation initiation and that the cap structure
      and the HAV IRES probably compete for the same limiting translation factors. The
      efficiency with which monocistronic constructs containing the HAV 5'NTR directed
      translation in reticulocyte lysates was compared with results for monocistronic
      constructs containing the IRES of the more rapidly growing encephalomyocarditis
      virus (EMCV). These results indicated that the HAV 5'NTR was more than 25-fold
      less active than the EMCV IRES in producing translation product. HAV 5'NTR
      directed translation was inhibited by the presence of a one-fifth molar quantity
      of RNA containing the EMCV IRES, while a fivefold molar excess of the HAV 5'NTR
      did not inhibit EMCV IRES-directed translation. The relatively weak activity of
      the HAV IRES may thus be due to a reduced affinity for cellular translation
      factors which are present in limiting quantities in rabbit reticulocyte lysate.

PMID- 8289337
TI  - A mutant baculovirus with a temperature-sensitive IE-1 transregulatory protein.
AB  - We have mapped the mutation responsible for the temperature-sensitive (ts)
      phenotype of tsB821, a mutant of the baculovirus Autographa californica nuclear
      polyhedrosis virus (H. H. Lee and L. K. Miller, J. Virol. 31:240-252, 1979), to a
      single nucleotide which changes alanine 432 of the multifunctional regulatory
      protein IE-1 to a valine. Mapping was done with a combination of marker rescue
      and transient expression assays, hybrid gene construction by overlap PCR gene
      splicing, and nucleotide sequence analysis. Cells infected with tsB821 at high
      multiplicities of infection showed a spectrum of responses from severe cytopathic
      effects, including apoptosis, to a lack of obvious signs of infection. Protein
      synthesis in tsB821-infected cells at the restrictive temperature appeared
      similar to uninfected cell protein synthesis, but viral DNA replication and
      budded virus production were observed, albeit in a delayed manner. The dependence
      of early and late promoter activity on the wild-type IE-1 gene, ie-1, was
      observed in transient expression assays. However, the dependence of early
      promoter activity on ie-1 was strongest in the absence of other viral genes.
      Thus, other viral genes appear to be able to compensate, at least in part, for
      the lack, or low levels, of ie-1 in transient expression assays using early
      promoters. The mutant should prove useful in further defining the function(s) of
      IE-1.

PMID- 8289338
TI  - The bovine papillomavirus type 1 (BPV1) replication protein E1 modulates
      transcriptional activation by interacting with BPV1 E2.
AB  - The study of bovine papillomavirus type 1 (BPV1) DNA replication has shown that
      E1 and E2 are the only viral proteins required for this process. Both E1 and E2
      interact with the viral origin of replication (ori). The BPV1 E2 protein is also
      a well-characterized transcriptional regulator. We show in this report that E1
      can modulate transcription by interactions with E2. At low concentrations, E1
      enhanced the E2-mediated transactivation of heterologous promoters containing the
      BPV1 ori by promoting cooperative binding of both E1 and E2 to the DNA. In
      contrast, in the presence of excess E1, transactivation by E2 is repressed. This
      last process, however, does not require cooperative DNA binding of the two
      proteins. These results imply that the balance between these two distinct types
      of interaction is crucial both for control of replication and for early viral
      transcription.

PMID- 8289339
TI  - DNA binding specificity of the bovine papillomavirus E1 protein is determined by
      sequences contained within an 18-base-pair inverted repeat element at the origin
      of replication.
AB  - Bovine papillomavirus type 1 (BPV-1) DNA replicates episomally and requires two
      virally expressed proteins, E1 and E2, for this process. Both proteins bind to
      the BPV-1 genome in the region that functions as the origin of replication. The
      binding sequences for the E2 protein have been characterized previously, but
      little is known about critical sequence requirements for E1 binding. Using a
      bacterially expressed E1 fusion protein, we examined binding of the BPV-1 E1
      protein to the origin region. E1 strongly protected a 28-bp segment of the origin
      (nucleotides 7932 to 15) from both DNase I and exonuclease III digestion.
      Additional exonuclease III protection was observed beyond the core region on both
      the 5' and 3' sides, suggesting that E1 interacted with more distal sequences as
      well. Within the 28-bp protected core, there were two overlapping imperfect
      inverted repeats (IR), one of 27 bp and one of 18 bp. We show that sequences
      within the smaller, 18-bp IR element were sufficient for specific recognition of
      DNA by E1 and that additional BPV-1 sequences beyond the 18-bp IR element did not
      significantly increase origin binding by E1 protein. While the 18-bp IR element
      contained sequences sufficient for specific binding by E1, E1 did not form a
      stable complex with just the isolated 18-bp element. Formation of a detectable E1
      DNA complex required that the 18-bp IR be flanked by additional DNA sequences.
      Furthermore, binding of E1 to DNA containing the 18-bp IR increased as a function
      of overall increasing fragment length. We conclude that E1-DNA interactions
      outside the boundaries of the 18-bp IR are important for thermodynamic
      stabilization of the E1-DNA complex. However, since the flanking sequences need
      not be derived from BPV-1, these distal E1-DNA interactions are not sequence
      specific. Comparison of the 18-bp IR from BPV-1 with the corresponding region
      from other papillomaviruses revealed a symmetric conserved consensus sequence, T
      RY--TTAA--RY-A, that may reflect the specific nucleotides critical for E1-DNA
      recognition.

PMID- 8289340
TI  - Assembly of vaccinia virus: effects of rifampin on the intracellular distribution
      of viral protein p65.
AB  - The cytoplasmic assembly of vaccinia virus is reversibly blocked by the
      antibiotic rifampin, leading to the accumulation of partially membrane-delineated
      rifampin bodies in infected cells. Rifampin-resistant vaccinia virus mutants have
      point mutations in the D13L gene, which is controlled by a late promoter and
      expresses a 65-kDa protein, designated p65. To further characterize the mechanism
      of rifampin inhibition and the function of p65 in virus assembly, we raised
      antibodies to this protein. Immunoreactive p65 was expressed at late times of
      infection, and neither its expression nor its turnover was affected by rifampin.
      Virus-associated p65 could be extracted only with denaturing detergents from
      purified virions, suggesting that it is an integral viral component.
      Immunofluorescence studies showed that p65 is localized to the sites of virus
      assembly. Also, immunoelectron microscopy showed p65 to be associated with viral
      crescents as well as spherical, immature virions, in both cases predominantly on
      the inner or concave surface. In the presence of rifampin, p65 was found in
      large, cytoplasmic inclusion bodies that were distinct from rifampin bodies. The
      rifampin bodies themselves were labeled with p65 antibodies only after reversal
      of the rifampin block, predominantly on the viral crescents which rapidly formed
      following removal of the drug. We propose that p65 functions as an internal
      scaffold in the formation of viral crescents and immature virions, analogously to
      the matrix proteins of other viruses.

PMID- 8289341
TI  - Human papillomavirus type 11 E2 proteins repress the homologous E6 promoter by
      interfering with the binding of host transcription factors to adjacent elements.
AB  - The E6 promoter of human papillomaviruses (HPVs) trophic for epithelia for the
      lower genital tract and the upper respiratory tract is regulated in vitro by
      homologous and heterologous papillomaviral E2 proteins that bind to a consensus
      responsive sequence (E2-RS) ACCN6GGT. When HPV type 11 (HPV-11) expression is
      examined in epithelial cell lines, the HPV-11 E2-C protein, which lacks the amino
      terminal transactivating domain of the full-length E2 protein, invariably
      represses the homologous viral E6 promoter. In contrast, when the novel
      constitutive enhancer (CE) CE II is deleted, not only is the basal promoter
      activity much reduced, it is further repressed by the intact HPV-11 E2 protein
      (M. T. Chin, T. R. Broker, and L. T. Chow, J. Virol. 63:2967-2976, 1989). Here,
      we demonstrated that, when expressed from a stronger surrogate promoter, the HPV
      11 E2 protein represses the E6 promoter effectively, regardless of CE II. By
      performing systematic mutational analyses of the four highly conserved copies of
      the HPV-11 E2-RS and of the adjacent enhancer-promoter elements, we show that the
      furthest upstream, promoter-distal E2-RS copy 1 plays no apparent role in E6
      promoter regulation. Repression by the homologous HPV-11 E2 proteins is mediated
      through each of the three promoter-proximal copies of the E2-RS, but the presence
      of CE II abrogates the full-length E2 protein repression exerted at E2-RS copy 2.
      Repression is alleviated when the two (for E2) or three (for E2-C) promoter
      proximal copies of E2-RS are mutated. We specifically demonstrate that repression
      exerted at E2-RS 3 is due to preclusion of binding of the host transcription
      factor Sp1 or Sp1-like proteins to a nonconsensus sequence AGGAGG located 1 bp
      upstream of the tandem E2 protein binding sites 3 and 4. A 3-bp insertion between
      the adjacent Sp1 and E2-RS 3 sites permits both Sp1 and E2 proteins to bind, with
      a concomitant relief of E2-RS 3-mediated repression. Similar mutational analyses
      show that proteins that bind to the GT-1 motif near the upstream E2-RS 2 help
      abrogate repression by the E2 protein in the presence of CE II. The implications
      of these results with respect to the viral infectious cycle and during viral
      oncogenesis are discussed.

PMID- 8289342
TI  - In vitro replication of adeno-associated virus DNA.
AB  - The study of eukaryotic viral DNA replication in vitro has led to the
      identification of cellular enzymes involved in DNA replication. Adeno-associated
      virus (AAV) is distinct from previously reported systems in that it is believed
      to replicate entirely by leading-strand DNA synthesis and requires coinfection
      with adenovirus to establish completely permissive replication. In previous work,
      we demonstrated that two of the AAV nonstructural proteins, Rep78 and -68, are
      site-specific endonucleases and DNA helicases that are capable of resolving
      covalently closed AAV termini, a key step in AAV DNA replication. We have now
      cloned the AAV nonstructural proteins Rep78, Rep68, and Rep52 in the baculovirus
      expression system. Using the baculovirus-expressed proteins, we have developed an
      efficient in vitro AAV DNA replication system which mimics the in vivo behavior
      of AAV in every respect. With no-end AAV DNA as the starting substrate, the
      reaction required an adenovirus-infected cell extract and the presence of either
      Rep78 or Rep68. Rep52, as expected, did not support DNA replication. A mutant in
      the AAV terminal resolution site (trs) was defective for DNA replication in the
      in vitro assay. Little, if any, product was formed in the absence of the
      adenovirus-infected HeLa cell extract. In general, uninfected HeLa extracts were
      less efficient in supporting AAV DNA replication than adenovirus-infected
      extracts. Thus, the requirement for adenovirus infection in vivo was partially
      duplicated in vitro. The reduced ability of uninfected HeLa extracts to support
      complete DNA replication was not due to a defect in terminal resolution but
      rather to a defect in the reinitiation reaction or in elongation. Rep78 produced
      a characteristic monomer-dimer pattern of replicative intermediates, but
      surprisingly, Rep68 produced little, if any, dimer replicative form. The reaction
      had a significant lag (30 min) before incorporation of 32P-deoxynucleoside
      triphosphate could be detected in DpnI-resistant monomer replicative form and was
      linear for at least 4 h after the lag. The rate of incorporation in the reaction
      was comparable to that in the simian virus 40 in vitro system. Replication of the
      complete AAV DNA molecule was demonstrated by the following criteria. (i) Most of
      the monomer and dimer product DNAs were completely resistant to digestion with
      DpnI. (ii) Virtually all of the starting substrate was converted to heavy-light
      or heavy-heavy product DNA in the presence of bromo-dUTP when examined on CsCl
      density gradients.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8289344
TI  - Helix-destabilizing properties of the adenovirus DNA-binding protein.
AB  - The adenovirus DNA-binding protein (DBP) is a multifunctional protein that is
      essential for viral DNA replication. DBP binds both single-stranded and double
      stranded DNA as well as RNA in a sequence-independent manner. Previous studies
      showed that DBP does not promote melting of duplex poly(dA-dT) in contrast to
      prokaryotic single-strand-binding proteins. However, here we show that DBP can
      displace oligonucleotides annealed to single-stranded M13 DNA. Depending upon the
      DBP concentration, strands of at least 200 nucleotides can be unwound. Although
      unwinding of short (17-bp), fully duplex DNA is facilitated by DBP, unwinding of
      larger (28-bp) duplexes is only possible if single-stranded protruding ends are
      present. These protruding ends must be at least 4 nucleotides long for optimal
      unwinding, and both 5' and 3' single-stranded overhangs suffice. DBP-promoted
      strand displacement is sensitive to MgCl2 and NaCl and not dependent upon ATP.
      Our results suggest that DBP, through formation of a protein chain on the
      displaced strand, may destabilize duplex DNA ahead of the replication fork,
      thereby assisting in strand displacement during replication.

PMID- 8289343
TI  - Correlation between fusogenicity of synthetic modified peptides corresponding to
      the NH2-terminal extremity of simian immunodeficiency virus gp32 and their mode
      of insertion into the lipid bilayer: an infrared spectroscopy study.
AB  - The amino-terminal extremity of the simian immunodeficiency virus (SIV)
      transmembrane protein (gp32) has been shown to play a pivotal role in cell-virus
      fusion and syncytium formation. We provide here evidence of a correlation between
      the structure and orientation of the modified SIV fusion peptide after insertion
      into the lipid membrane and its fusogenic activity. The sequence of the wild-type
      SIV peptide has been modified in such a way that the calculated angles of
      insertion correspond to an oblique, parallel, or normal orientation with respect
      to the lipid-water interface. Fourier transform infrared spectroscopy was used to
      gain experimental informations about the structures and orientations, of the
      membrane-inserted peptides with respect to the lipid acyl chains. The peptides
      adopt mainly a beta-sheet conformation in the absence of lipids. After
      interaction with large unilamellar liposomes, this beta sheet is partly converted
      into alpha helix. The ability of the modified peptides to promote lipid mixing
      was assessed by a fluorescence energy transfer assay. The data provide evidence
      that alpha-helix formation is not sufficient to induce lipid mixing and that the
      fusogenic activity of the peptide depends on its orientation in the lipid
      bilayer.

PMID- 8289345
TI  - Radiation leukemia virus-induced thymic lymphomas express a restricted repertoire
      of T-cell receptor V beta gene products.
AB  - We have investigated the phenotypic changes that take place during the process of
      neoplastic transformation in the thymocytes of C57BL/Ka mice infected by the
      radiation leukemia virus (RadLV). By the combined use of antibodies against the
      envelope glycoprotein gp70 of RadLV, the transformation-associated cell surface
      marker 1C11, and the CD3-T-cell receptor (TCR) complex, we found that in the
      RadLV-infected thymus, the earliest expression of viral gp70 is in 1C11hi cells;
      a small but significant percentage of these cells also express CD3. A first wave
      of viral replication, manifested by the expression of high levels of gp70 in
      thymocytes (over 70% positive), reaches a peak at 2 weeks; during this period, no
      significant changes are observed in the expression of 1C11 or CD3. The population
      of gp70+ cells is drastically reduced at 3 to 4 weeks after infection. However, a
      second cohort of gp70+ cells appears after 4 weeks, and these cells express high
      levels of 1C11 and TCR determinants as well. RadLV-induced lymphomas differ from
      normal thymocytes in their CD4 CD8 phenotype, with domination by one or more
      subsets. Characterization of TCR gene rearrangements in RadLV-induced lymphomas
      shows that most of these tumors are clonal or oligoclonal with respect to the J
      beta 2 TCR gene, while the J beta 1 TCR gene is rearranged in a minority (4 of
      11) of lymphomas. TCR V beta repertoire analysis of 12 tumors reveals that 6
      (50%) express exclusively the V beta 6 gene product, 2 (17%) are V beta 5+, and 1
      (8%) each are V beta 8+ and V beta 9+. In normal C57BL/Ka mice, V beta 6 is
      expressed on 12%, V beta 5 is expressed on 9%, V beta 8 is expressed on 22%, and
      V beta 9 is expressed on 4% of TCRhi thymocytes. Thus, it appears that RadLV
      induced thymic lymphomas are not randomly selected with respect to expressed TCR
      V beta type.

PMID- 8289347
TI  - Fusion from without directed by human immunodeficiency virus particles.
AB  - Fusion from without is the process through which particles of some enveloped
      viruses can direct fusion of target cells in the absence of viral replication. We
      demonstrate here that human immunodeficiency virus (HIV) particles can
      efficiently promote fusion from without. Using HeLa-CD4 cells carrying a Tat
      inducible lacZ gene, we observed syncytia as early as 6 h after exposure to HIV
      particles, before HIV gene expression could be detected. Efficient syncytium
      formation could be obtained when cells were treated with zidovudine, which
      prevented HIV replication and expression but not cell-cell fusion. Fusion was
      also observed when cells were exposed to particles of a replication-defective HIV
      integrase mutant. Fusion from without by HIV particles could be blocked by a
      monoclonal antibody specific for the V3 loop of the HIV-1 envelope glycoprotein
      and by soluble CD4. This mechanism of cytopathicity, which can involve cells that
      do not actively replicate HIV and can be directed by replication-defective
      particles, could participate in the pathogenicity of the CD4 cell depletion that
      characterizes HIV infection.

PMID- 8289346
TI  - Human herpesvirus 6 infects cervical epithelial cells and transactivates human
      papillomavirus gene expression.
AB  - To examine whether human herpesvirus 6 (HHV-6) is capable of infecting human
      cervical epithelial cells and altering expression of human papillomavirus (HPV)
      genes, HPV-immortalized or -transformed carcinoma cell lines were infected with
      HHV-6 variant A. No cytopathic effect was observed in infected cervical cells.
      However, immunofluorescence indicated that infected cells expressed early-late
      proteins of HHV-6 by day 3 postinfection. HHV-6 DNA was also detected by Southern
      blot hybridization after infection and persisted through continued subculture in
      an episomal state as proven by Gardella gel electrophoresis and fluorescence in
      situ hybridization. HHV-6 infection enhanced expression of HPV RNAs encoding the
      viral oncoproteins E6 and E7. Transient transfection assays showed that two HHV-6
      molecular clones, pZVB-70 and pZVH-14, upregulated transcription 9- to 15-fold
      from a receptor plasmid containing the HPV type 18 regulatory sequences which
      control transcription in vivo. Cervical carcinoma cells infected with HHV-6
      induced more rapid development of tumors in mice than did noninfected cells.
      These results are the first evidence that human cervical epithelial cells can be
      infected with HHV-6 and that HHV-6 contains transactivators which stimulate the
      HPV-transforming genes.

PMID- 8289348
TI  - In vivo and in vitro analyses of recombinant baculoviruses lacking a functional
      cg30 gene.
AB  - The cg30 gene of Autographa californica nuclear polyhedrosis virus (AcMNPV)
      encodes two sequence motifs, a zinc finger-like motif and a leucine zipper, found
      in other polypeptides known to be involved in gene regulation. To gain insight
      into the function of the cg30 product, CG30, we constructed and characterized
      recombinant viruses lacking a functional cg30 gene. We found that cg30 mutants
      had no striking phenotype in cell lines derived from Spodoptera frugiperda or
      Trichoplusia ni or in T. ni larvae. Although cg30 is known to be transcribed as
      an early monocistronic RNA and as the second cistron of an abundant late
      bicistronic RNA, production of a CG30-beta-galactosidase fusion protein was
      observed mainly at early times postinfection. Viruses containing cg30 had a
      subtle growth advantage over those lacking cg30 after several viral passages in
      cell culture. We employed transient expression assays to determine whether cg30
      and pe-38, an AcMNPV gene that encodes a polypeptide with zinc finger-like and
      leucine zipper motifs similar to those of cg30, have redundant functions.
      Although pe-38 may have a role in AcMNPV gene expression, there was no indication
      that cg30 and pe-38 are functionally redundant.

PMID- 8289349
TI  - Characterization of a Marek's disease virus BamHI-L-specific cDNA clone obtained
      from a Marek's disease lymphoblastoid cell line.
AB  - Two Marek's disease (MD) virus BamHI-L-specific cDNA clones were isolated from a
      cDNA library constructed from poly(A)+ RNA fractions of an MD lymphoblastoid cell
      line, MDCC-CU41 (CU41). These clones were mapped to the region corresponding to
      the BamHI-Q2 and L-regions. These clones hybridized with 2.5-, 0.8-, and 0.6-kb
      transcripts prepared from CU41. The transcriptional unit of the 0.6-kb transcript
      was determined by RNase protection assays. An open reading frame encoding a 107
      amino-acid polypeptide was identified in the 0.6-kb transcript. Reverse
      transcriptase-PCR demonstrated the presence of this transcript in both CU41 and a
      reticuloendotheliosis virus-transformed cell line latently infected with MD
      virus.

PMID- 8289350
TI  - Mutations of polyomavirus VP1 allow in vitro growth in undifferentiated cells and
      modify in vivo tissue replication specificity.
AB  - Mutants of polyomavirus with altered host specificities were isolated in
      undifferentiated C2 myoblast cells (L. Ricci, R. Maione, C. Passananti, A.
      Felsani, and P. Amati, J. Virol. 66:7153-7158, 1992). The mutations responsible
      for this phenotype belonged to either of the two classes: a large duplication of
      the enhancer region or a 6-bp deletion in the VP1 coding region. Since both
      classes of mutations enabled the virus to grow in undifferentiated myoblast
      cells, we investigated their ability to replicate in embryonal carcinoma cells
      and in various tissues in newborn mice. Our results show that both kinds of
      mutations confer the ability to replicate in vitro in embryonal carcinoma F9
      cells; the VP1 mutants acquired an in vivo host range of replication which is
      different from that of their original wild-type strain, whereas the mutation in
      the regulatory region did not alter the in vivo growth spectrum.

PMID- 8289351
TI  - Different activation of Epstein-Barr virus immediate-early and early genes in
      Burkitt lymphoma cells and lymphoblastoid cell lines.
AB  - Specific expression of the Epstein-Barr virus (EBV) immediate-early and early
      gene products Zta, Rta, I'ta, and MSta by a recombinant vaccinia virus system
      allowed us to analyze the first steps in the induction of the lytic cycle in EBV
      infected Burkitt lymphoma (BL) cells and lymphoblastoid cell lines (LCLs).
      Significant differences in the induction of early genes were found between these
      cell types: whereas in BL cells the trans activator Zta was found to induce key
      steps of the early lytic cycle, only minor activities of Zta were noted in LCLs.
      Contrary to Zta, the trans activator Rta was found to be highly effective in
      LCLs. These observations suggest that Rta may play an important role in the
      activation of the early lytic cycle in LCLs, although it cannot be activated by
      Zta. The latter may be a reason for the lower tendency of LCLs to switch into the
      lytic cycle compared with BL cells or differentiated epithelial cells.

PMID- 8289352
TI  - Adenovirus-dependent release of choline from plasma membrane vesicles at an
      acidic pH is mediated by the penton base protein.
AB  - It has been suggested that during receptor-mediated endocytosis of human
      adenovirus (Ad) type 2 into cells, Ad disrupts the membrane of endocytic vesicles
      to enter the cytosol. To understand the mechanism of Ad-mediated disruption of
      the endocytic vesicles, I exposed Ad to plasma membrane vesicles derived from KB
      cells. Ad caused release of choline from the plasma membrane vesicles preloaded
      with [3H]choline. The efflux of choline was dependent on (i) the concentration of
      Ad, with a half-maximal effect at 0.5 microgram/ml; (ii) the pH of the buffer,
      with the optimum pH of the reaction ranging from 5.5 to 6.0; (iii) the length of
      the incubation, with a half-maximal release at 2 min; and (iv) the temperature of
      the incubation, with the optimum temperature being 37 degrees C. The Ad-dependent
      release of choline was inhibited by anti-penton base, while antihexon did not
      block the effect. These results suggest roles for a low-pH environment and the
      penton base protein in the Ad-dependent efflux of choline from plasma membrane
      vesicles.

PMID- 8289353
TI  - Sequences present in the cytoplasmic domain of CD4 are necessary and sufficient
      to confer sensitivity to the human immunodeficiency virus type 1 Vpu protein.
AB  - CD4 is an integral membrane glycoprotein which functions as the human
      immunodeficiency virus receptor for infection of human host cells. We have
      recently demonstrated that Vpu, a human immunodeficiency virus type 1-encoded
      integral membrane phosphoprotein, induces rapid degradation of CD4 in the
      endoplasmic reticulum. Using an in vitro model system, we demonstrated that Vpu
      targets specific sequences in the cytoplasmic domain of CD4 to promote its
      degradation. In this report, we have further delineated regions within CD4 which
      are required for susceptibility to Vpu. Transfer of the CD4 cytoplasmic region
      into a heterologous protein, CD8, rendered the chimeric protein sensitive to Vpu
      dependent degradation. In contrast, substitution of the CD8 transmembrane domain
      with the analogous region from CD4 did not confer sensitivity to Vpu. Finally,
      mutant forms of the CD4 protein containing the extracellular region alone or the
      extracellular and transmembrane regions linked to a heterologous cytoplasmic
      domain were not targeted by Vpu. Thus, sequences present in the cytoplasmic
      domain of CD4 are necessary and sufficient to confer sensitivity to Vpu.

PMID- 8289354
TI  - Sequence specificity of furin, a proprotein-processing endoprotease, for the
      hemagglutinin of a virulent avian influenza virus.
AB  - The virulence of avian influenza viruses correlates with the sensitivity of their
      hemagglutinin (HA) to cellular proteases. Furin, a proprotein-processing
      subtilisin-related endoprotease, is a leading candidate for the enzyme that
      cleaves the HA of virulent avian viruses. We therefore compared the specificity
      of furin with those of proteases in a variety of cultured cells and in a rat
      Golgi fraction, using the HA cleavage mutants of a virulent avian influenza
      virus, A/Turkey/Ireland/1378/85 (H5N8). The results indicated similar sequence
      specificities among the endoproteases when purified furin was used. In
      experiments with the vaccinia virus expression system, overexpressed furin
      cleaved mutant HAs that were not recognized by the endogenous proteases,
      resulting in an apparent broader specificity of furin. These findings
      authenticate the proposed role of furin as an HA-activating protease in vivo and
      caution against the use of expression vectors to study protease sequence
      specificity.

PMID- 8289355
TI  - Importance of amino acid 101 within capsid protein VP1 for modulation of
      Theiler's virus-induced disease.
AB  - We constructed a Theiler's virus mutant designated DA3304, in which the amino
      acid at position 101 of VP1 was changed from a threonine to an alanine. Because
      of this single amino acid change, DA3304 could still produce a biphasic central
      nervous system disease similar to that produced by the wild-type DA virus.
      However, DA3304 was significantly attenuated in both the acute and the chronic
      phases and induced smaller demyelinating lesions than the wild-type DA virus. The
      data are most compatible with the attenuated phenotype in DA3304 being due to the
      change of binding efficiency between the virus and receptor resulting from the
      physical alteration at the mutation site.

PMID- 8289356
TI  - Herpesvirus-induced cell fusion that is dependent on cell surface heparan sulfate
      or soluble heparin.
AB  - The entry of enveloped viruses into animal cells and the cell-to-cell spread of
      infection via cell fusion require the membrane-fusing activity of viral
      glycoproteins. This activity can be dependent on variable cell factors or
      triggered by environmental factors. Here we show that cell fusion induced by
      herpes simplex virus glycoproteins is dependent on the presence of cell surface
      glycosaminoglycans, principally heparan sulfate, or on the addition of heparin to
      the medium. The role of the glycosaminoglycan is probably to alter the
      conformation of a viral heparin-binding glycoprotein required for the fusion.

PMID- 8289357
TI  - Adeno-associated virus type 2 rep gene-mediated inhibition of basal gene
      expression of human immunodeficiency virus type 1 involves its negative
      regulatory functions.
AB  - Adeno-associated virus type 2 (AAV-2), a human parvovirus which is apathogenic in
      adults, inhibits replication and gene expression of human immunodeficiency virus
      type 1 (HIV-1) in human cells. The rep gene of AAV-2, which was shown earlier to
      be sufficient for this negative interference, also down-regulated the expression
      of heterologous sequences driven by the long terminal repeat (LTR) of HIV-1. This
      effect was observed in the absence of the HIV-1 transactivator Tat, i.e., at
      basal levels of LTR-driven transcription. In this work, we studied the
      involvement of functional subsequences of the HIV-1 LTR in rep-mediated
      inhibition in the absence of Tat. Mutated LTRs driving an indicator gene (cat)
      were cointroduced into human SW480 cells together with rep alone or with double
      stranded DNA fragments or RNA containing sequences of the HIV-1 LTR. The results
      indicate that rep strongly enhances the function of negative regulatory elements
      of the LTR. In addition, the experiments revealed a transcribed sequence element
      located within the TAR-coding sequence termed AHHH (AAV-HIV homology element
      derived from HIV-1) which is involved in rep-mediated inhibition. The AHHH
      element is also involved in down-regulation of basal expression levels in the
      absence of rep, suggesting that AHHH also contributes to negative regulatory
      functions of the LTR of HIV-1. In contrast, positive regulatory elements of the
      HIV-1 LTR such as the NF kappa B and SP1 binding sites have no significant
      influence on the rep-mediated inhibition.

PMID- 8289358
TI  - YY1 is the cellular factor shown previously to bind to regulatory regions of
      several leaky-late (beta gamma, gamma 1) genes of herpes simplex virus type 1.
AB  - We have recently reported that a cellular factor, the leaky-late binding factor
      (LBF), binds to sites in a number of leaky-late (beta gamma or gamma 1) genes of
      herpes simplex virus type 1 and that an LBF site is essential for maximum viral
      transactivation of the major capsid protein (VP5) gene. The results of binding
      competition, partial proteolysis, and monoclonal antibody inhibition assays
      presented here establish that LBF is identical to the transcription factor YY1.
      This, along with our previous observations, suggests that YY1 plays a role in
      herpes simplex virus type 1 gene regulation.

PMID- 8289359
TI  - Adenovirus type 40 and 41 growth in vitro: host range diversity reflected by
      differences in patterns of DNA replication.
AB  - Subgroup F adenoviruses adapt poorly to cell culture, but the reasons for their
      fastidious nature are as yet ill defined. In an attempt to gain an overview of
      the differences in replication between adenovirus type 2 (Ad2) and representative
      strains of Ad40 and Ad41, cell lines which show different degrees of
      permissiveness to Ad40 and Ad41 were infected and examined with respect to three
      key functions in the Ad2 life cycle: host protein shutoff, DNA synthesis, and
      late antigen synthesis. The complexity of growth patterns exhibited by the
      subgroup F adenoviruses suggests that defectiveness is a multifactorial
      phenomenon not easily explainable by a single aberrant function. Furthermore,
      results suggest that there may be replicative defects in subgroup F adenoviruses
      which are not shared by both serotypes or by all strains.

PMID- 8289360
TI  - Role of neuraminidase in the morphogenesis of influenza B virus.
AB  - When ts7, a temperature-sensitive (ts) mutant of influenza B/Kanagawa/73 virus,
      infected MDCK cells at the nonpermissive temperature (37.5 degrees C), infectious
      virus was produced at very low levels compared with the yield at the permissive
      temperature (32 degrees C) and hemagglutinating activity and enzymatic activity
      of neuraminidase (NA) were negligible. However, viral protein synthesis and
      transport of hemadsorption-active hemagglutinin to the cell surface were not
      affected. When the cell lysate was treated with bacterial NA, hemagglutinating
      activity was recovered but infectivity was not, even after further treatment with
      trypsin. It was found that ts7 was defective in transport of NA to the cell
      surface and formation of virus particles. Analysis of the genomes of non-ts
      recombinants obtained by crossing ts7 and UV-inactivated B/Lee showed that ts7
      had the ts mutation only in RNA segment 6 coding for NA and the glycoprotein NB.
      Nucleotide sequence analysis of the RNA segment revealed that ts7 had four amino
      acid changes in the NA molecule but not in NB. We suggest that assembly or
      budding of influenza B virus requires the presence of NA at the plasma membrane,
      unlike influenza A virus.

PMID- 8289361
TI  - Association of bluetongue virus gene segment 5 with neuroinvasiveness.
AB  - Two strains (UC-2 and UC-8) of bluetongue virus were used to determine genetic
      factors influencing neuroinvasiveness. Reassortants were produced in vitro, and
      the parental origins of their genes were determined by polyacrylamide gel
      electrophoresis profiles and restriction endonuclease digestion. Gene segment 5
      of UC-8 correlated with neuroinvasiveness of reassortants when inoculated
      subcutaneously into newborn mice.

PMID- 8289362
TI  - Truncation of the cytoplasmic domain of the simian immunodeficiency virus
      envelope glycoprotein alters the conformation of the external domain.
AB  - We previously reported that truncation of the cytoplasmic domain of the macaque
      simian immunodeficiency virus SIVmac239 envelope glycoprotein enhanced its
      ability to induce cell fusion in a variety of cell lines. In the present study,
      we examined the expression of the full-length and truncated SIVmac239 envelope
      glycoprotein complex on cell surfaces. Using a membrane-impermeable reagent to
      biotinylate proteins on cell surfaces followed by immunoprecipitation, we found
      that under conditions in which the full-length TM protein could not be detected
      on the surfaces of CD4-positive or CD4-negative cell lines, the truncated TM
      protein was detected efficiently. In contrast, using a membrane-impermeable
      iodination reagent to label proteins on cell surfaces, we could detect both the
      full-length and truncated TM proteins. No difference between the full-length and
      truncated proteins was observed in the detection of the SU proteins in the
      biotinylation assay. Additionally, we used an assay in which SIV-specific
      antibodies are prebound to the native envelope proteins expressed on the cell
      surface and then the proteins are immunoprecipitated. Using this assay, we could
      not detect the truncated or full-length TM protein on the cell surface, whereas
      we could detect the SU subunits of both proteins. We also observed that the
      truncated TM protein formed more stable sodium dodecyl sulfate-resistant
      oligomers than the full-length TM protein did. These results indicate that
      truncation of the cytoplasmic domain of the SIVmac239 envelope glycoprotein
      affects the conformation of the external domain of the TM protein on the cell
      surface, even though the two proteins have no differences in the amino acid
      sequences of their external domains. This altered conformation could play a role
      in the enhanced fusion activity of the truncated SIV glycoprotein.

PMID- 8289363
TI  - A novel hantavirus associated with an outbreak of fatal respiratory disease in
      the southwestern United States: evolutionary relationships to known hantaviruses.
AB  - Four Corners hantavirus (FCV) is the tentative name of the suspected etiologic
      agent of the newly identified hantavirus-associated respiratory distress syndrome
      (HARDS). The identification in HARDS patients of serum immunoglobulin M and
      immunoglobulin G antibodies that cross-reacted with Hantaan, Seoul, and Puumala
      virus antigens first suggested that FCV is a hantavirus. Limited nucleotide
      sequence data from the FCV glycoprotein-2 (G2) confirmed that FCV is a hantavirus
      and showed that it is most closely related to Prospect Hill and Puumala viruses.
      We have molecularly cloned approximately 95% of the sequences of the M and S
      segments of the FCV genome encoding the envelope glycoproteins and nucleocapsid
      protein N from the lungs of a patient with HARDS. The nucleotide sequence has
      been determined for 2,632 bases. The nucleotide sequence data show that FCV is a
      new member of the Puumala virus and Prospect Hill virus division of the
      hantavirus genus. Phylogenetic tree analyses indicate that the M and S segments
      have evolved in parallel. Therefore, the novel pathogenic activity of FCV is not
      likely to be the result of recent reassortment of segments from less pathogenic
      viruses.

PMID- 8289364
TI  - Nucleotide sequence analysis of a 38.5-kilobase-pair region of the genome of
      human herpesvirus 6 encoding human cytomegalovirus immediate-early gene homologs
      and transactivating functions.
AB  - Human herpesvirus 6 (HHV-6) is prevalent in the human population, with primary
      infection occurring early in life. Its predominant CD4+ T-lymphocyte tropism, its
      ability to activate human immunodeficiency virus type 1 (HIV-1) gene expression
      in vitro, and its upregulation of CD4 expression has led to speculation that HHV
      6 may act as a positive cofactor in the progression of HIV infection to AIDS in
      individuals infected with both viruses. Previous sequencing studies of restricted
      regions of the 161.5-kbp genome of HHV-6 have demonstrated unequivocally that it
      is a member of the betaherpesvirus subgroup and have indicated that the HHV-6
      genome is generally collinear with the unique long (UL) component of human
      cytomegalovirus (HCMV). In the work described in this report we have extended
      these sequencing studies by determining the primary structure of 38.5-kbp of the
      HHV-6 genome (genomic position 21.0 to 59.5 kbp). Within the sequenced region lie
      31 open reading frames, 20 of which are homologous to positional counterparts in
      HCMV. Of particular significance is the identification of homologs of the HCMV
      UL36-38 and US22-type genes, which have been shown to encode transactivating
      proteins. We show that DNA sequences encoding these HHV-6 homologs were able to
      transactivate HIV-1 long terminal repeat-directed chloramphenicol
      acetyltransferase expression in cotransfection assays, thus demonstrating
      functional as well as structural conservation of these betaherpesvirus-specific
      gene products. Our data therefore confirm the close relationship between HHV-6
      and HCMV and identify putative immediate-early regulatory genes of HHV-6 likely
      to play key roles in lytic replication and possibly also in the interactions
      between HHV-6 and HIV in dually infected cells.

PMID- 8289365
TI  - Interaction of human papillomavirus (HPV) type 16 capsid proteins with HPV DNA
      requires an intact L2 N-terminal sequence.
AB  - Encapsidation of papillomavirus DNA involves DNA-protein and protein-protein
      interactions. We sought to define the role of each human papillomavirus (HPV)
      capsid protein in HPV DNA encapsidation. HPV16 major (L1) and minor (L2) capsid
      proteins purified from recombinant vaccinia virus-infected cells were compared
      for their ability to bind nucleic acids. L2 protein, but not L1 protein, could
      bind HPV DNA. To map the DNA-binding region of L2, a series of truncated or point
      mutated L2 protein open reading frames were used to show that only the N terminal
      of L2 was required for L2-DNA binding. This interaction depends critically on
      charged amino acids (Lys or Arg) in the first 12 amino acids of the N terminal of
      the protein. Several techniques were used to show that L2 interaction with DNA
      did not require specific DNA sequences. We propose that HPV L2 protein may play a
      major role in papillomavirus capsid assembly by introducing HPV DNA to the virus
      particles formed by the self assembly of the L1 major structural protein.

PMID- 8289366
TI  - Glycosylation-dependent inactivation of the ecotropic murine leukemia virus
      receptor.
AB  - The ecotropic murine leukemia virus (E-MuLV) receptor expressed on Mus dunni tail
      fibroblast (MDTF) cells is a receptor for all E-MuLVs with the notable of Moloney
      murine leukemia virus (Mo-MuLV). Substitution of isoleucine for valine at
      position 214 in the third extracellular region (the putative E-MuLV binding site)
      of the MDTF receptor molecule allows this molecule to function as a Mo-MuLV
      receptor (M.V. Eiden, K. Farrell, J. Warsowe, L. A. Mahan, and C. A. Wilson, J.
      Virol. 67:4056-4061, 1993). We have now determined that treating MDTF cells with
      tunicamycin, an inhibitor of N-linked glycosylation, also renders them
      susceptible to Mo-MuLV infection. Two potential N-linked glycosylation sites are
      present in the third extracellular regions of both the NIH 3T3 and MDTF ecotropic
      receptors. The glycosylation site at position 229 of the MDTF receptor cDNA was
      eliminated by substituting a threonine codon for the asparagine codon. Mo-MuLV
      resistant human HOS cells, expressing this form of the receptor, are susceptible
      to Mo-MuLV infection. Thus, our studies suggest that without a glycan moiety at
      position 229, the valine residue at 214 is no longer restrictive for Mo-MuLV
      infection. BHK-21 and CHO K1 hamster cells also express glycosylation-inactivated
      forms of the ecotropic receptor. Sequence analysis of these receptors together
      with our analysis of MDTF receptor function suggests that a single asparagine
      linked glycosylation site is responsible for glycosylation inactivation of these
      receptors.

PMID- 8289367
TI  - The human foamy virus internal promoter directs the expression of the functional
      Bel 1 transactivator and Bet protein early after infection.
AB  - The human foamy virus or spumaretrovirus (HFV) is a complex retrovirus that has
      the capacity to code not only for the three retroviral genes gag, pol, and env
      but, in addition, for at least three bel genes. The HFV provirus contains two
      different and functionally active promoters: the classical retroviral promoter in
      the 5' long terminal repeat and a recently identified second promoter in the env
      gene upstream of the bel genes. Both promoter/enhancers are strongly dependent on
      the HFV transcriptional transactivator protein Bel 1. Here we report that the
      internal promoter directs the synthesis of viral transcripts that code for
      functionally active Bel 1 and for Bet proteins that appeared early after HFV
      infection. The viral mRNAs of the internal promoter have a 112-nucleotide-long
      leader exon and were spliced predominantly at the first splice donor site in the
      5' untranslated region. The data were obtained by transient expression assays,
      transactivation experiments, and RNA analyses of transcripts derived from HFV
      infected cells. The results provide strong evidence for the crucial role the
      internal promoter plays during HFV infection in generating bel-specific
      transcripts.

PMID- 8289368
TI  - Mutational analysis of delta antigen: effect on assembly and replication of
      hepatitis delta virus.
AB  - Hepatitis delta virus requires a helper function from hepatitis B virus for
      packaging, release, and infection of hepatocytes. The assembly of large delta
      antigen (HDAg) is mediated by copackaging with the small surface antigen of
      hepatitis B virus (HBsAg), and the assembly of small HDAg requires interactions
      with large HDAg. To examine the molecular mechanisms by which small HBsAg, large
      HDAg, and small HDAg interact, we have established a virion assembly system in
      COS7 cells by cotransfecting plasmids encoding the small HBsAg, the small HDAg,
      and large HDAg mutants. Results indicate that sequences within the C-terminal 19
      amino-acid domain flanking the Cxxx isoprenylation motif are important for the
      assembly of large HDAg. In addition, a large HDAg mutant bearing extra sequences
      separating the C-terminal 19-amino-acid domain from the common regions of the
      small and large HDAgs is capable, like the wild-type large HDAg, of copackaging
      with small HBsAg. The ability of assembly is also demonstrated for a large HDAg
      mutant from which nuclear localization signals have been removed. Furthermore, a
      cryptic signal within the N-terminal 50 amino acid residues other than the
      putative N-terminal coiled-coil structure and a subdomain between amino acid
      residues 50 and 65 of the large HDAg are important for the assembly of small HDAg
      as well as the trans-dominant negative regulation of large HDAg in hepatitis
      delta virus replication.

PMID- 8289369
TI  - A small and efficient dimerization/packaging signal of rat VL30 RNA and its use
      in murine leukemia virus-VL30-derived vectors for gene transfer.
AB  - Retroviral genomes consist of two identical RNA molecules associated at their 5'
      ends by the dimer linkage structure located in the packaging element (Psi or E)
      necessary for RNA dimerization in vitro and packaging in vivo. In murine leukemia
      virus (MLV)-derived vectors designed for gene transfer, the Psi + sequence of 600
      nucleotides directs the packaging of recombinant RNAs into MLV virions produced
      by helper cells. By using in vitro RNA dimerization as a screening system, a
      sequence of rat VL30 RNA located next to the 5' end of the Harvey mouse sarcoma
      virus genome and as small as 67 nucleotides was found to form stable dimeric RNA.
      In addition, a purine-rich sequence located at the 5' end of this VL30 RNA seems
      to be critical for RNA dimerization. When this VL30 element was extended by 107
      nucleotides at its 3' end and inserted into an MLV-derived vector lacking MLV Psi
      +, it directed the efficient encapsidation of recombinant RNAs into MLV virions.
      Because this VL30 packaging signal is smaller and more efficient in packaging
      recombinant RNAs than the MLV Psi + and does not contain gag or glyco-gag coding
      sequences, its use in MLV-derived vectors should render even more unlikely
      recombinations which could generate replication-competent viruses. Therefore,
      utilization of the rat VL30 packaging sequence should improve the biological
      safety of MLV vectors for human gene transfer.

PMID- 8289370
TI  - Characterization of an immortalizing N-terminal domain of polyomavirus large T
      antigen.
AB  - Polyomavirus large T antigen has an N-terminal domain of approximately 260 amino
      acids which can immortalize primary cells but lacks sequences known to be
      required for DNA binding and replication. Treatment of full-length large T with
      either V8 protease or chymotrypsin yields an N-terminal fragment of 36 to 40 kDa
      and a C-terminal fragment of approximately 60 kDa. This finding suggests a
      division of the protein into two domains. Proteolysis experiments show that the N
      terminal domain does not have strong physical association with the rest of the
      protein. It also does not self-associate. A construct expressing only the N
      terminal 259 amino acids is sufficient for immortalization. The independently
      expressed N-terminal domain is multiply phosphorylated, although at a lower level
      than the same region in full-length large T. The 259-residue protein binds to
      both pRb and p107 with somewhat lower efficiency than the full-length protein.

PMID- 8289371
TI  - Transgenic mice carrying the human poliovirus receptor: new animal models for
      study of poliovirus neurovirulence.
AB  - Recombinant viruses between the virulent Mahoney and attenuated Sabin 1 strains
      of poliovirus type 1 were subjected to neurovirulence tests using a transgenic
      (Tg) mouse line, ICR-PVRTg1, that carried the human poliovirus receptor gene. The
      Tg mice were inoculated intracerebrally with these recombinant viruses and
      observed for clinical signs, histopathological lesions, and viral antigens as
      parameters of neurovirulence of the viruses. These parameters observed in the Tg
      mice were different for different inoculated viruses. Dose-dependent incidences
      of paralysis and of death were observed in the Tg mice inoculated with any
      viruses used. This indicates that values of 50% lethal dose are useful to score a
      wide range of neurovirulence of poliovirus. The neurovirulence of individual
      viruses estimated by the Tg mouse model had a strong correlation with those
      estimated by monkey model. Consequently, the mouse tests identified the
      neurovirulence determinants on the genome of poliovirus that had been identified
      by monkey tests. In addition, the mouse tests revealed new neurovirulence
      determinants, that is, different nucleotides between the two strains at positions
      189 and 21 and/or 935 in the 5'-proximal 1,122 nucleotides. The Tg mice used in
      this study may be suitable for replacing monkeys for investigating poliovirus
      neurovirulence.

PMID- 8289372
TI  - Immunization with replication-defective mutants of herpes simplex virus type 1:
      sites of immune intervention in pathogenesis of challenge virus infection.
AB  - Replication-defective mutants of herpes simplex virus type 1 (HSV-1) were used as
      a new means to immunize mice against HSV-1-mediated ocular infection and disease.
      The effects of the induced immune responses on pathogenesis of acute and latent
      infection by challenge virus were investigated after corneal inoculation of
      immunized mice with virulent HSV-1. A single subcutaneous injection of
      replication-defective mutant virus protected mice against development of
      encephalitis and keratitis. Replication of the challenge virus at the initial
      site of infection was lower in mice immunized with attenuated, wild-type parental
      virus (KOS1.1) or replication-defective mutant virus than in mice immunized with
      uninfected cell extract or UV-inactivated wild-type virus. Significantly, latent
      infection in the trigeminal ganglia was reduced in mice given one immunization
      with replication-defective mutant virus and was completely prevented by two
      immunizations. Acute replication in the trigeminal ganglia was also prevented in
      mice immunized twice with wild-type or mutant virus. The level of protection
      against infection and disease generated by immunization with replication
      defective mutant viruses was comparable to that of infectious wild-type virus in
      all cases. In addition, T-cell proliferative and neutralizing antibody responses
      following immunization and corneal challenge were of similar strength in mice
      immunized with replication-defective mutant viruses or with wild-type virus.
      Thus, protein expression by forms of HSV-1 capable of only partially completing
      the replication cycle can induce an immune response in mice that efficiently
      decreases primary replication of virulent challenge virus, interferes with acute
      and latent infection of the nervous system, and inhibits the development of both
      keratitis and systemic neurologic disease.

PMID- 8289373
TI  - trans complementation by RNA of defective foot-and-mouth disease virus internal
      ribosome entry site elements.
AB  - A region of about 435 bases from the 5' noncoding region of foot-and-mouth
      disease virus RNA directs internal initiation of protein synthesis. This region,
      termed the internal ribosome entry site (IRES), is predicted to contain extensive
      secondary structure. Precise deletion of five predicted secondary structure
      features has been performed. The mutant IRES elements have been constructed into
      vectors which express bicistronic mRNAs and assayed within cells. Each of the
      modified IRES elements was defective in directing internal initiation when
      assayed alone. However, coexpression of an intact foot-and-mouth disease virus
      IRES complemented four of these defective elements to an efficiency of up to 80%
      of wild-type activity. No complementation was observed with the structurally
      analogous element from encephalomyocarditis virus. The role of RNA-RNA
      interactions in the function of the picornavirus IRES is discussed.

PMID- 8289374
TI  - Subcellular localization of the Vif protein of human immunodeficiency virus type
      1.
AB  - The Vif (viral infectivity factor) protein of human immunodeficiency virus type 1
      (HIV-1) has been shown to dramatically enhance the infectivity of HIV-1 virus
      particles during virus production. The subcellular localization of Vif was
      examined to elucidate cellular pathways which may be important for Vif function.
      Indirect immunofluorescence staining of Vif demonstrated a diffuse cytoplasmic
      distribution and showed that most Vif was not associated with the Golgi complex,
      a proposed site of localization (B. Guy, M. Geist, K. Dott, D. Spehner, M.-P.
      Kieny, and J.-P. Lecocq, J. Virol. 65:1325-1331, 1991). Subcellular fractionation
      of transfected COS cells and HIV-1-infected Jurkat and CEM cells demonstrated
      that Vif is a cytoplasmic protein which exists in both a soluble cytosolic form
      and membrane-associated form. The membrane-associated form of Vif is a peripheral
      membrane protein which is tightly associated with the cytoplasmic side of
      cellular membranes. The C terminus of Vif was required for the stable association
      of Vif with membranes. The C terminus was also essential for Vif function,
      suggesting that the association of Vif with membranes is likely to be important
      for its biological activity. The highly conserved regions at residues 103 to 115
      and 142 to 150 were important for Vif function but did not affect membrane
      association, indicating that these regions are likely to be important for other,
      as-yet-unknown functions.

PMID- 8289375
TI  - Rescue of synthetic genomic RNA analogs of rabies virus by plasmid-encoded
      proteins.
AB  - Proteins entirely expressed from cDNA were used to rescue synthetic RNA genome
      analogs into infectious defective particles of rabies virus (RV). Synthetic
      negative-stranded RNAs containing 3'- and 5'-terminal RV sequences and
      transcriptional signal sequences were transcribed from plasmids transfected into
      cells expressing T7 RNA polymerase from recombinant vaccinia virus. After
      simultaneous expression of RV N, P, and L proteins from plasmids containing a T7
      RNA polymerase promoter, the synthetic genomes were encapsidated, replicated, and
      transcribed by the RV polymerase proteins. Insertion of the bacterial
      chloramphenicol acetyltransferase gene or beta-galactosidase (lacZ) gene between
      the 3' and 5' termini containing transcriptional signal sequences resulted in
      transcription of mRNAs and expression of chloramphenicol acetyltransferase and
      beta-galactosidase, respectively. Upon simultaneous expression of N, P, M, G, and
      L proteins, virions carrying the foreign genes were assembled and released into
      the supernatant. The possibility of rescuing cDNA into rabies virions by proteins
      also expressed entirely from cDNA opens the possibility of studying the functions
      of each RV protein and analyzing cis-acting signals of the RV genome.

PMID- 8289376
TI  - The human cytomegalovirus 86-kilodalton immediate-early 2 protein: synthesis as a
      precursor polypeptide and interaction with a 75-kilodalton protein of probable
      viral origin.
AB  - The immediate-early 2 (IE2) 86-kDa polypeptide, a major immediate-early gene
      product of human cytomegalovirus, regulates transcription both positively and
      negatively. We report two new properties of the IE2 86-kDa polypeptide in
      infected cells. Immunoprecipitation of infected cell proteins from human
      embryonic lung cells by antipeptide or monoclonal antibodies specific for IE2
      epitopes revealed three closely migrating polypeptide species. The slowest, p86,
      behaved as expected for the mature 86-kDa IE2 polypeptide. The middle species,
      p80, was immunoprecipitated from denatured as well as native samples and labeled
      to steady state rapidly. Pulse-chase analysis demonstrated directly that p80 was
      a metabolic precursor to p86. The fastest-migrating species, p75, was not
      detected by probing blots of the immunoprecipitated proteins with IE2-specific
      antisera; p75 was not precipitated from denatured protein samples; and the
      products of partial proteolysis of p75 were distinct from those of p86. These
      properties established p75 as an unrelated coprecipitated polypeptide complexed
      with p86. The p75 proteins coprecipitated from cells infected with two different
      strains of human cytomegalovirus, AD169 and Towne, had different mobilities. p75
      was detected as early as 6 h and as late as 72 h after infection, but it was not
      synthesized in cells released from a cycloheximide block. Thus, it is likely that
      p75 is an early viral protein.

PMID- 8289377
TI  - Pathogenesis of Aleutian mink disease parvovirus infection: effects of
      suppression of antibody response on viral mRNA levels and on development of acute
      disease.
AB  - We suppressed the B-cell development and antibody response in mink by using
      treatment with polyclonal anti-immunoglobulin M (anti-IgM) to study the effects
      of antiviral antibodies on development of Aleutian mink disease parvovirus (ADV)
      induced disease in more detail. Newborn mink kits were injected intraperitoneally
      with 1 mg of either anti-IgM or a control preparation three times a week for 30
      to 34 days. At 21 days after birth, groups of mink kits were infected with the
      highly virulent United isolate of ADV. At selected time points, i.e.,
      postinfection days 9, 13, 29, and 200, randomly chosen mink kits were sacrificed,
      and blood and tissues were collected for analyses. The efficacy of
      immunosuppressive treatment was monitored by electrophoretic techniques and flow
      cytometry. Effects of treatment on viral replication, on viral mRNA levels, and
      on development of acute or chronic disease were determined by histopathological,
      immunoelectrophoretic, and molecular hybridization techniques. Several
      interesting findings emerged from these studies. First, antiviral antibodies
      decreased ADV mRNA levels more than DNA replication. Second, suppression of B
      cell development and antibody response in mink kits infected at 21 days of age
      resulted in production of viral inclusion bodies in alveolar type II cells. Some
      of these kits showed mild clinical signs of respiratory disease, and one kit died
      of respiratory distress; however, clinical signs were seen only after release of
      immunosuppression, suggesting that the production of antiviral antibodies, in
      combination with the massive amounts of free viral antigen present, somehow is
      involved in the induction of respiratory distress. It is suggested that the
      antiviral antibody response observed in mink older than approximately 14 days
      primarily, by a yet unknown mechanism, decreases ADV mRNA levels which, if severe
      enough, results in restricted levels of DNA replication and virion production.
      Furthermore, such a restricted ADV infection at low levels paves the way for a
      persistent infection leading to immunologically mediated disease. The potential
      mechanisms of antibody-mediated restriction of viral mRNA levels and mechanisms
      of disease induction are discussed.

PMID- 8289378
TI  - Sequence diversity within the reovirus S2 gene: reovirus genes reassort in
      nature, and their termini are predicted to form a panhandle motif.
AB  - To better understand genetic diversity within mammalian reoviruses, we determined
      S2 nucleotide and deduced sigma 2 amino acid sequences of nine reovirus strains
      and compared these sequences with those of prototype strains of the three
      reovirus serotypes. The S2 gene and sigma 2 protein are highly conserved among
      the four type 1, one type 2, and seven type 3 strains studied. Phylogenetic
      analyses based on S2 nucleotide sequences of the 12 reovirus strains indicate
      that diversity within the S2 gene is independent of viral serotype. Additionally,
      we found marked topological differences between phylogenetic trees generated from
      S1 and S2 gene nucleotide sequences of the seven type 3 strains. These results
      demonstrate that reovirus S1 and S2 genes have distinct evolutionary histories,
      thus providing phylogenetic evidence for lateral transfer of reovirus genes in
      nature. When variability among the 12 sigma 2-encoding S2 nucleotide sequences
      was analyzed at synonymous positions, we found that approximately 60 nucleotides
      at the 5' terminus and 30 nucleotides at the 3' terminus were markedly conserved
      in comparison with other sigma 2-encoding regions of S2. Predictions of RNA
      secondary structures indicate that the more conserved S2 sequences participate in
      the formation of an extended region of duplex RNA interrupted by a pair of stem
      loops. Among the 12 deduced sigma 2 amino acid sequences examined, substitutions
      were observed at only 11% of amino acid positions. This finding suggests that
      constraints on the structure or function of sigma 2, perhaps in part because of
      its location in the virion core, have limited sequence diversity within this
      protein.

PMID- 8289379
TI  - Antiviral activity of human immunodeficiency virus type 1 protease inhibitors in
      a single cycle of infection: evidence for a role of protease in the early phase.
AB  - The antiviral activities of two substrate-based inhibitors of human
      immunodeficiency virus type 1 (HIV-1) protease, UK-88,947 and Ro 31-8959, were
      studied in acute infections. H9 and HeLaCD4-LTR/beta-gal cells were infected
      either with HIV-1IIIB or a replication-defective virus, HIV-gpt(HXB-2). Both
      inhibitors were capable of blocking early steps of HIV-1 replication if added to
      cells prior to infection. Partial inhibition was also obtained by addition of
      inhibitor at the time of or as late as 15 min after infection. The inhibitors
      were ineffective if added 30 min postinfection. The inhibitory effects were
      studied by cDNA analysis with PCR followed by Southern blot hybridization and by
      infectivity assays allowing quantitation of HIV-1 in a single cycle of
      replication. When UK-88,947-treated H9 cells were coinfected with HIV-1 and human
      T-cell leukemia virus type I only the replication of HIV-1 was inhibited,
      demonstrating viral specificity. Pretreating the infectious virus stocks with the
      inhibitors also prevented replication, indicating that the inhibitors block the
      action of the viral protease and not a cellular protease. A panel of primer sets
      was used to analyze cDNA from cell lysates by PCR amplification at 4 and 18 h
      postinfection. Four hours after infection, viral specific cDNA was detected with
      all of the four primer pairs used: R/U5, nef/U3, 5' gag, and long terminal repeat
      (LTR)/gag. However, after 18 h, only the R/U5 and nef/U3 primer pairs and not the
      5' gag or LTR/gag primer pair were able to allow amplification of cDNA. The
      results suggest a crucial role of HIV-1 protease in the early phase of viral
      replication. Although it is not clear what early steps are affected by the
      protease, it is likely that the target is the NC protein, as referred from our
      previous reports of the in situ cleavage of the nucleocapsid (NC) protein by the
      viral protease inside lentiviral capsids. The results suggest that it is not the
      inhibition of initiation and progression of reverse transcription but the
      stability of full-size unintegrated cDNA which is affected in the presence of
      protease inhibitors. Alternatively, the cleavage of the NC protein may be
      required for the proper formation of preintegration complex and/or for its
      transport to the nucleus.

PMID- 8289380
TI  - High-level expression and purification of secreted forms of herpes simplex virus
      type 1 glycoprotein gD synthesized by baculovirus-infected insect cells.
AB  - Two forms of herpes simplex virus glycoprotein gD were recombined into Autographa
      californica nuclear polyhedrosis virus (baculovirus) and expressed in infected
      Spodoptera frugiperda (Sf9) cells. Each protein was truncated at residue 306 of
      mature gD. One form, gD-1(306t), contains the coding sequence of Patton strain
      herpes simplex virus type 1 gD; the other, gD-1(QAAt), contains three mutations
      which eliminate all signals for addition of N-linked oligosaccharides. Prior to
      recombination, each gene was cloned into the baculovirus transfer vector pVT-Bac,
      which permits insertion of the gene minus its natural signal peptide in frame
      with the signal peptide of honeybee melittin. As in the case with many other
      baculovirus transfer vectors, pVT-Bac also contains the promoter for the
      baculovirus polyhedrin gene and flanking sequences to permit recombination into
      the polyhedrin site of baculovirus. Each gD gene was engineered to contain codons
      for five additional histidine residues following histidine at residue 306, to
      facilitate purification of the secreted protein on nickel-containing resins. Both
      forms of gD-1 were abundantly expressed and secreted from infected Sf9 cells,
      reaching a maximum at 96 h postinfection for gD-1(306t) and 72 h postinfection
      for gD-1(QAAt). Secretion of the latter protein was less efficient than gD
      1(306t), possibly because of the absence of N-linked oligosaccharides from gD
      1(QAAt). Purification of the two proteins by a combination of immunoaffinity
      chromatography, nickel-agarose chromatography, and gel filtration yielded
      products that were > 99% pure, with excellent recovery. We are able to obtain 20
      mg of purified gD-1(306t) and 1 to 5 mg of purified gD-1(QAAt) per liter of
      infected insect cells grown in suspension. Both proteins reacted with monoclonal
      antibodies to discontinuous epitopes, indicating that they retain native
      structure. Use of this system for gD expression makes crystallization trials
      feasible.

PMID- 8289381
TI  - Phosphorylation at the carboxy terminus of the 55-kilodalton adenovirus type 5
      E1B protein regulates transforming activity.
AB  - The 55-kDa product of early region 1B (E1B) of human adenoviruses is required for
      viral replication and participates in cell transformation through complex
      formation with and inactivation of the cellular tumor suppressor p53. We have
      used both biochemical and genetic approaches to show that this 496-residue (496R)
      protein of adenovirus type 5 is phosphorylated at serine and threonine residues
      near the carboxy terminus within sequences characteristic of substrates of casein
      kinase II. Mutations which converted serines 490 and 491 to alanine residues
      decreased viral replication and greatly reduced the efficiency of transformation
      of primary baby rat kidney cells. Such mutant 496R proteins interacted with p53
      at efficiencies similar to those of wild-type 496R but only partially inhibited
      p53 transactivation activity. These results indicated that phosphorylation at
      these carboxy-terminal sites either regulates the inhibition of p53 or regulates
      some other 496R function required for cell transformation.

PMID- 8289382
TI  - The genomic instability associated with integrated simian virus 40 DNA is
      dependent on the origin of replication and early control region.
AB  - DNA rearrangements in the form of deletions and duplications are found within and
      near integrated simian virus 40 (SV40) DNA in nonpermissive cell lines. We have
      found that rearrangements also occur frequently with integrated pSV2neo plasmid
      DNA. pSV2neo contains the entire SV40 control region, including the origin of
      replication, both promoters, and the enhancer sequences. Linearized plasmid DNA
      was electroporated into X1, an SV40-transformed mouse cell line that expresses
      SV40 large T antigen (T Ag) and shows very frequent rearrangements at the SV40
      locus, and into LMtk-, a spontaneously transformed mouse cell line that contains
      no SV40 DNA. Stability was analyzed by subcloning G-418-resistant clones and
      examining specific DNA fragments for alterations in size. Five independent X1
      clones containing pSV2neo DNA were unstable at both the neo locus and the T Ag
      locus. By contrast, four X1 clones containing mutants of pSV2neo with small
      deletions in the SV40 core origin and three X1 clones containing a different neo
      plasmid lacking SV40 sequences were stable at the neo locus, although they were
      still unstable at the T Ag locus. Surprisingly, five independent LMtk- clones
      containing pSV2neo DNA were unstable at the neo locus. LMtk- clones containing
      origin deletion mutants were more stable but were not as stable as the X1 clones
      containing the same plasmid DNA. We conclude that the SV40 origin of replication
      and early control region are sufficient viral components for the genomic
      instability at sites of SV40 integration and that SV40 T Ag is not required.

PMID- 8289383
TI  - Biologically active Rep proteins of adeno-associated virus type 2 produced as
      fusion proteins in Escherichia coli.
AB  - Four Rep proteins are encoded by the human parvovirus adeno-associated virus type
      2 (AAV). The two largest proteins, Rep68 and Rep78, have been shown in vitro to
      perform several activities related to AAV DNA replication. The Rep78 and Rep68
      proteins are likely to be involved in the targeted integration of the AAV DNA
      into human chromosome 19, and the full characterization of these proteins is
      important for exploiting this phenomenon for the use of AAV as a vector for gene
      therapy. To obtain sufficient quantities for facilitating the characterization of
      the biochemical properties of the Rep proteins, the AAV rep open reading frame
      was cloned and expressed in Escherichia coli as a fusion protein with maltose
      binding protein (MBP). Recombinant MBP-Rep68 and MBP-Rep78 proteins displayed the
      following activities reported for wild-type Rep proteins when assayed in vitro:
      (i) binding to the AAV inverted terminal repeat (ITR), (ii) helicase activity,
      (iii) site-specific (terminal resolution site) endonuclease activity, (iv)
      binding to a sequence within the integration locus for AAV DNA on human
      chromosome 19, and (v) stimulation of radiolabeling of DNA containing the AAV ITR
      in a cell extract. These five activities have been described for wild-type Rep
      produced from mammalian cell extracts. Furthermore, we recharacterized the
      sequence requirements for Rep binding to the ITR and found that only the A and A'
      regions are necessary, not the hairpin form of the ITR.

PMID- 8289384
TI  - Formation and rearrangement of disulfide bonds during maturation of the Sindbis
      virus E1 glycoprotein.
AB  - The rigidly ordered icosahedral lattice of the Sindbis virus envelope is composed
      of a host-derived membrane bilayer in which the viral glycoproteins E1 and E2
      reside. E1-E1 interactions stabilized by intramolecular disulfide bridges play a
      significant role in maintaining the envelope's structural integrity (R. P.
      Anthony and D. T. Brown, J. Virol. 65:1187-1194, 1991; R. P. Anthony, A. M.
      Paredes, and D. T. Brown, Virology 190:330-336, 1992). We have examined the
      acquisition of disulfide bridges within E1 during its maturation. Prior to exit
      from the endoplasmic reticulum, E1 folds via at least three intermediates,
      differing in the number and/or arrangement of their disulfides, into a single,
      compact form. This E1 species remains stable with respect to its disulfides until
      late in the secretory pathway, when E1 attains a metastable conformation. At this
      point, when appropriately triggered, intramolecular thiol-disulfide exchange
      reactions within E1 can occur, resulting in the generation of alternative E1
      species. This metastable nature of mature E1 may have important implications for
      the mechanism of virus disassembly during the initial stages of the infection
      process (B. Abell and D. T. Brown, J. Virol. 67:5496-5501, 1993).

PMID- 8289385
TI  - A baculovirus gp64 early promoter is activated by host transcription factor
      binding to CACGTG and GATA elements.
AB  - The early promoter of the Orgyia pseudotsugata multicapsid nuclear polyhedrosis
      virus gp64 gene is active when transfected into several insect cell lines and
      does not require viral gene products for transcription in uninfected cells.
      Because previous studies have shown that the gp64 early promoter is activated
      above basal levels in uninfected cells, host transcription factors are likely to
      play a role in gp64 activation at early times postinfection. By using nuclear
      extracts from uninfected Sf9 cells for electrophoretic mobility shift analysis of
      gp64 regulatory regions, host nuclear proteins were shown to bind specifically to
      the upstream regulatory region of the gp64 early promoter. Host factor binding
      was mapped to a 24-bp sequence centered approximately 35 bp upstream of the TATA
      box. Two consensus eukaryotic transcription factor-binding site motifs, GATA and
      CACGTG, were identified within the 24-bp sequence. Competition assays using
      oligonucleotides containing either a GATA or a CACGTG motif and similar
      oligonucleotides with point mutations in these sites showed that each site is
      required for binding host transcription factors. To investigate the functional
      significance of host factor binding to GATA and CACGTG motifs, constructs
      containing point mutations in these motifs were examined in transient expression
      assays. Mutations in either or both GATA and CACGTG sites decreased reporter
      activity in transient expression assays, suggesting that binding of host
      transcription factors to these motifs is important in transcriptional regulation
      of the gp64 early promoter.

PMID- 8289386
TI  - Amino acid substitution mutations in the herpes simplex virus ICP27 protein
      define an essential gene regulation function.
AB  - ICP27 is an essential herpes simplex virus type 1 (HSV-1) alpha protein that is
      required for the transition from the beta to the gamma phase of infection. To
      identify functional regions of ICP27, we constructed 16 plasmids that contain
      nucleotide substitution mutations in the ICP27 gene. The mutations created XhoI
      restriction sites, altered one or two codons, and were spaced at semiregular
      intervals throughout the coding region. Three mutations completely inactivated an
      essential function of ICP27, as demonstrated by the inability of the transfected
      plasmids to complement the growth of an HSV-1 ICP27 deletion mutant. These
      mutations, M11, M15, and M16, mapped in the carboxyl-terminal one-third of ICP27
      at residues 340 and 341, 465 and 466, and 488, respectively. In cotransfection
      assays, all three defective-plasmid mutants retained the transrepression function
      of ICP27 but were defective at transactivation. To define the lytic functions
      that are mediated by the transactivation activity of ICP27, we engineered HSV-1
      recombinants containing the M11, M15, or M16 mutation. All three viral mutants
      failed to grow in Vero cells and possessed similar phenotypes. The viral mutants
      replicated their DNA similarly to the wild-type virus but showed several defects
      in viral gene expression. These were a failure to down-regulate alpha and beta
      genes at late times after infection and an inability to induce certain gamma-2
      genes. Our results demonstrate that the transactivation function of ICP27 (as it
      is defined in cotransfection assays) mediates an essential gene regulation
      function during the HSV-1 infection. This activity is not required for ICP27
      dependent enhancement of viral DNA replication. Our work supports and extends
      previous studies which suggest that ICP27 carries out two distinct regulatory
      activities during the HSV-1 infection.

PMID- 8289387
TI  - Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo
      and across junctions of cultured cells.
AB  - Herpes simplex virus (HSV) glycoproteins E and I (gE and gI) can act as a
      receptor for the Fc domain of immunoglobulin G (IgG). To examine the role of HSV
      IgG Fc receptor in viral pathogenesis, rabbits and mice were infected by the
      corneal route with HSV gE- or gI- mutants. Wild-type HSV-1 produced large
      dendritic lesions in the corneal epithelium and subsequent stromal disease
      leading to viral encephalitis, whereas gE- and gI- mutant viruses produced
      microscopic punctate or small dendritic lesions in the epithelium and no corneal
      disease or encephalitis. These differences were not related to the ability of the
      gE-gI oligomer to bind IgG because the differences were observed before the
      appearance of anti-HSV IgG and in mice, in which IgG binds to the Fc receptor
      poorly or not at all. Mutant viruses produced small plaques on monolayers of
      normal human fibroblasts and epithelial cells. Replication of gE- and gI- mutant
      viruses in human fibroblasts were normal, and the rates of entry of mutant and
      wild-type viruses into fibroblasts were similar; however, spread of gE- and gI-
      mutant viruses from cell to cell was significantly slower than that of wild-type
      HSV-1. In experiments in which fibroblast monolayers were infected with low
      multiplicities of virus and multiple rounds of infection occurred, the presence
      of neutralizing antibodies in the culture medium caused the yields of mutant
      viruses to drop dramatically, whereas there was a lesser effect on the production
      of wild-type HSV. It appears that cell-to-cell transmission of wild-type HSV-1
      occurs by at least two mechanisms: (i) release of virus from cells and entry of
      extracellular virus into a neighboring cell and (ii) transfer of virus across
      cell junctions in a manner resistant to neutralizing antibodies. Our results
      suggest that gE- and gI- mutants are defective in the latter mechanism of spread,
      suggesting the possibility that the gE-gI complex facilitates virus transfer
      across cell junctions, a mode of spread which may predominate in some tissues. It
      is ironic that the gE-gI complex, usually considered an IgG Fc receptor, may,
      through its ability to mediate cell-to-cell spread, actually protect HSV from IgG
      in a manner different than previously thought.

PMID- 8289388
TI  - Molecular evolution of the major capsid protein VP1 of enterovirus 70.
AB  - Nucleotide sequences of the genome RNA encoding capsid protein VP1 (918
      nucleotides) of 18 enterovirus 70 (EV70) isolates collected from various parts of
      the world in 1971 to 1981 were determined, and nucleotide substitutions among
      them were studied. The genetic distances between isolates were calculated by the
      pairwise comparison of nucleotide difference. Regression analysis of the genetic
      distances against time of isolation of the strains showed that the synonymous
      substitution rate was very high at 21.53 x 10(-3) substitution per nucleotide per
      year, while the nonsynonymous rate was extremely low at 0.32 x 10(-3)
      substitution per nucleotide per year. The rate estimated by the average value of
      synonymous and nonsynonymous substitutions (W.-H. Li, C.-C. Wu, and C.-C. Luo,
      Mol. Biol. Evol. 2:150-174, 1985) was 5.00 x 10(-3) substitution per nucleotide
      per year. Taking the average value of synonymous and nonsynonymous substitutions
      as genetic distances between isolates, the phylogenetic tree was inferred by the
      unweighted pairwise grouping method of arithmetic average and by the neighbor
      joining method. The tree indicated that the virus had evolved from one focal
      place, and the time of emergence was estimated to be August 1967 +/- 15 months, 2
      years before first recognition of the pandemic of acute hemorrhagic
      conjunctivitis. By superimposing every nucleotide substitution on the branches of
      the phylogenetic tree, we analyzed nucleotide substitution patterns of EV70
      genome RNA. In synonymous substitutions, the proportion of transitions, i.e.,
      C<==>U and G<==>A, was found to be extremely frequent in comparison with that
      reported on other viruses or pseudogenes. In addition, parallel substitutions
      (independent substitutions at the same nucleotide position on different branches,
      i.e., different isolates, of the tree) were frequently found in both synonymous
      and nonsynonymous substitutions. These frequent parallel substitutions and the
      low nonsynonymous substitution rate despite the very high synonymous substitution
      rate described above imply a strong restriction on nonsynonymous substitution
      sites of VP1, probably due to the requirement for maintaining the rigid
      icosahedral conformation of the virus.

PMID- 8289389
TI  - Clustered charged-to-alanine mutagenesis of poliovirus RNA-dependent RNA
      polymerase yields multiple temperature-sensitive mutants defective in RNA
      synthesis.
AB  - To generate a collection of conditionally defective poliovirus mutants, clustered
      charged-to-alanine mutagenesis of the RNA-dependent RNA polymerase 3D was
      performed. Clusters of charged residues in the polymerase coding region were
      replaced with alanines by deoxyoligonucleotide-directed mutagenesis of a full
      length poliovirus cDNA clone. Following transfection of 27 mutagenized cDNA
      clones, 10 (37%) gave rise to viruses with temperature-sensitive (ts) phenotypes.
      Three of the ts mutants displayed severe ts plaque reduction phenotypes,
      producing at least 10(3)-fold fewer plaques at 39.5 degrees C than at 32.5
      degrees C; the other seven mutants displayed ts small-plaque phenotypes. Constant
      temperature, single-cycle infections showed defects in virus yield or RNA
      accumulation at the nonpermissive temperature for eight stable ts mutants. In
      temperature shift experiments, seven of the ts mutants showed reduced
      accumulation of viral RNA at the nonpermissive temperature and showed no other ts
      defects. The mutations responsible for the phenotypes of most of these ts mutants
      lie in the N-terminal third of the 3D coding region, where no well-characterized
      mutations responsible for viable mutants had been previously identified.
      Clustered charged-to-alanine mutagenesis (S. H. Bass, M. G. Mulkerrin, and J. A.
      Wells, Proc. Natl. Acad. Sci. USA 88:4498-4502, 1991; W. F. Bennett, N. F. Paoni,
      B. A. Keyt, D. Botstein, J. J. S. Jones, L. Presta, F. M. Wurm, and M. J. Zoller,
      J. Biol. Chem. 266:5191-5201, 1991; and K. F. Wertman, D. G. Drubin, and D.
      Botstein, Genetics 132:337-350, 1992) is designed to target residues on the
      surfaces of folded proteins; thus, extragenic suppression analysis of such mutant
      viruses may be very useful in identifying components of the viral replication
      complex.

PMID- 8289390
TI  - Constructing chimeric type 12/type 5 adenovirus E1A genes and using them to
      identify an oncogenic determinant of adenovirus type 12.
AB  - The E1A gene of highly oncogenic type 12 adenovirus (Ad12) possesses a segment
      unique to this serotype and comprising 60 base pairs contiguous with and
      separating conserved regions 2 and 3 in the gene. A similar but slightly longer
      segment is also present in the E1A gene of highly oncogenic simian adenovirus
      type 7 (D. Kimelman, J. S. Miller, D. Porter, and B. E. Roberts, J. Virol. 53:399
      409, 1985). This segment is missing entirely from the E1A gene of type 5
      adenovirus, which is nononcogenic. To test the hypothesis that this unique
      separating or "spacer" region influences the oncogenicity of Ad12, we constructed
      ClaI and SmaI restriction sites on either side of it, which allowed reciprocal
      exchange between this and the equivalent cassette from type 5 adenovirus E1A,
      bounded by the same restriction sites intrinsic to that gene. The resultant Ad12
      based chimeric viruses, ch702 and ch704, in which the spacer region is replaced
      with (in-frame) type 5 sequence, grow normally on human A549 cells and display
      wild-type transformation frequencies on baby rat and mouse kidney cells. In
      contrast, the oncogenic capacity of these chimeric viruses, as measured by tumor
      induction following virus inoculation in Hooded Lister rats, is greatly reduced.
      Likewise, cells transformed by ch702 and ch704 display reduced tumorigenicity
      compared with wild-type transformants in syngeneic rats. These results, coupled
      with recent preliminary tests using a mutant with a point mutation in this
      region, support the view that the unique spacer region of type 12 is an oncogenic
      determinant of this virus.

PMID- 8289391
TI  - Tumorigenicity of adenovirus-transformed rodent cells is influenced by at least
      two regions of adenovirus type 12 early region 1A.
AB  - Chimeric adenovirus type 5 (Ad5)/Ad12 early region 1A (E1A) genes were used to
      transform primary baby rat kidney cells in cooperation with Ad12 E1B, and the
      resulting cell lines were assayed for tumorigenicity in syngeneic rats. It was
      found that lines were nontumorigenic when transformed by hybrid E1A genes
      consisting of the amino-terminal 80 amino acids from Ad12 including conserved
      region 1 (CR1), with the remaining portion from Ad5. In contrast, cell lines
      transformed by hybrids containing Ad12 E1A sequences from the amino terminus to
      the leftmost border of CR3 or beyond were tumorigenic. To extend these results,
      sequences spanning CR2 and CR3 of Ad5 E1A were replaced with the homologous
      regions of Ad12 E1A and additional transformed cell lines were established. These
      lines were weakly-to-moderately tumorigenic, suggesting that Ad12 E1A sequences
      between CR2 and CR3 may be involved in tumorigenicity but are not the sole
      factors influencing it. Interestingly, examination of an E1A sequence alignment
      indicated that the region between CR2 and CR3 of Ad12 E1A is also conserved in
      the corresponding sequence of simian adenovirus type 7, which, like Ad12, is
      highly oncogenic. This region is characterized by the presence of a stretch of
      several alanine residues and is similar to a motif present in a number of
      proteins with transcriptional repression activity. The possibility that this
      region may influence tumorigenicity by means of a transcriptional regulatory
      mechanism is discussed.

PMID- 8289392
TI  - An immunodominant Kb-restricted peptide from the p15E transmembrane protein of
      endogenous ecotropic murine leukemia virus (MuLV) AKR623 that restores
      susceptibility of a tumor line to anti-AKR/Gross MuLV cytotoxic T lymphocytes.
AB  - H-2b tumor cells expressing the endogenous ecotropic murine leukemia virus (EMV)
      induce an anti-AKR/Gross murine leukemia virus (MuLV) cytotoxic T-lymphocyte
      (CTL) response in the C57BL/6 mouse strain. The EMV clone AKR623 has been used to
      infect SC.Kb fibroblast cells, resulting in SC.Kb/623 targets that are lysed by
      bulk anti-AKR/Gross MuLV CTL with a profile that is similar to that for the EMV+
      AKR.H-2b SL1 tumor target. Anti-AKR/Gross MuLV CTL are restricted by the class I
      Kb antigen and do not cross-react with Friend-Moloney-Rauscher virus-positive
      targets. The AKR623 genome was searched by computer for coding sequences that fit
      the motif XXXX(FY)XX(VIML) for peptides that bind Kb. Of 30 octameric peptides
      identified, 12 that were unique to AKR623 and different from published Friend
      Moloney-Rauscher sequences were synthesized and bound to EMV-negative SC.Kb
      cells, which were then assayed as targets against anti-AKR/Gross MuLV CTL. One
      peptide, peptide 12 (KSPWFTTL) from the p15E transmembrane protein, sensitized
      SC.Kb target cells to lysis by anti-AKR/Gross MuLV CTL with a profile similar to
      those seen for AKR.H-2b SL1 tumor targets and SC.Kb/623 fibroblast targets. Low
      concentrations of peptide were sufficient, the half-maximal lysis occurring at 10
      to 100 pg/ml. SC.Kb/peptide 12 targets were recognized by the H-2b-restricted
      bulk CTL in a conventional class I Kb-restricted fashion. Unlabeled SC.Kb/peptide
      12-pulsed targets were effective in competing with radiolabeled SC.Kb/623 targets
      for lysis by anti-AKR/Gross MuLV CTL. This finding is consistent with the notion
      that peptide 12 represents the dominant endogenously processed epitope recognized
      by these antiviral CTL. In addition, peptide 12 is immunogenic in that it could
      stimulate the in vitro generation of an anti-AKR/Gross MuLV CTL response from
      tumor-primed C57BL/6 responder spleen cells. Finally, the physiological relevance
      of peptide 12 was suggested by its ability to fully restore the recognition and
      lysis of AKR.H-2b SL1 clone 18-5 tumor cells, a naturally occurring variant tumor
      clone that is insusceptible to lysis by anti-AKR/Gross MuLV CTL. These data
      indicate that a virus-encoded antigen, represented by peptide 12, and not a
      nonviral tumor antigen, is the immunodominant epitope responsible for the
      recognition of EMV+ tumor cells by C57BL/6-derived anti-AKR/Gross MuLV CTL.

PMID- 8289393
TI  - Human transcription factor YY1 represses human immunodeficiency virus type 1
      transcription and virion production.
AB  - The transcriptional activity of human immunodeficiency virus type 1 (HIV-1) is
      affected by many cellular factors. Homologies near the HIV-1 initiator region to
      the DNA-binding sequences of YY1, a multifunctional transcription factor known to
      regulate diverse viral and cellular promoters, suggested that YY1 might regulate
      HIV-1. Antibody to YY1 blocked the formation of complexes by HeLa cell nuclear
      extract and a DNA oligonucleotide encoding the HIV-1 initiator region. HIV-1 long
      terminal repeat (LTR) expression, as measured the expression of a transfected LTR
      CAT reporter gene, was repressed more than 12-fold by the cotransfection of a YY1
      expression vector. HIV-1 production by both COS-1 and CEM cells after
      transfection of an infectious molecular HIV-1 clone was repressed 7- to 20-fold
      by cotransfection of a YY1 expression vector. HIV-1 production was also decreased
      threefold in a CD4-positive lymphocyte cell line chronically infected with HIV-1
      (8E5) after transfection of YY1. In situ hybridization studies confirmed that YY1
      reduced HIV-1 RNA expression. YY1 may play an important role in the regulation of
      HIV-1 LTR expression in vivo and virus production by infected cells.

PMID- 8289395
TI  - Vaccine potential of a herpes simplex virus type 1 mutant with an essential
      glycoprotein deleted.
AB  - Several approaches to the production of vaccines to human herpesviruses have been
      proposed. Subunit vaccines, subunits delivered by live vectors, and rationally
      attenuated vaccines have all been shown to be efficacious in animal models but
      suffer from uncertainties as to the roles of individual genes involved in
      pathogenesis and the most relevant components of the immune response required for
      protection in humans and the target antigens involved. With these problems in
      mind, we examined the vaccine potential of a fully disabled herpes simplex virus
      type 1 mutant that is capable of only a single round of replication, since a
      virus of this type should induce the full spectrum of immune responses but has no
      pathogenic potential. A virus has been described which lacks essential
      glycoprotein H (gH) and can be propagated in a cell line which supplies gH in
      trans (A. Forrester, H. Farrell, G. Wilkinson, J. Kaye, N. Davis-Poynter, and T.
      Minson, J. Virol. 66:341-348, 1992). Infection of normal cells with this mutant
      is indistinguishable from a wild-type infection, except that the resulting
      progeny are gH negative and noninfectious: the virus is self-limiting. Infection
      of mice by the ear pinna route was similarly self-limiting in that input
      infectivity decreased rapidly at the inoculation site and no infectivity was
      detected in sensory ganglia. Animals given a wide range of doses of the gH
      negative mutant produced both humoral and T-cell responses to herpes simplex
      virus type 1 and proved solidly resistant to challenge with a high dose of wild
      type virus. The gH-negative mutant is presumably capable of establishing a latent
      infection, but since no infectious virus was detected in numerous attempts to
      reactivate the mutant, the risk of a pathogenic outcome is minimal.

PMID- 8289394
TI  - Rescue of vector-expressed fowl plague virus hemagglutinin in biologically active
      form by acidotropic agents and coexpressed M2 protein.
AB  - The hemagglutinin of the Rostock strain of fowl plague virus was expressed in CV
      1 cells by a simian virus 40 vector, and its stability in the exocytotic
      transport process was examined by a fusion assay. A 50-fold increase in the
      fusion activity of the hemagglutinin was observed when expression occurred in the
      presence of ammonium chloride, Tris-HCl, or high doses of amantadine. When
      chloroquine, another acidotropic agent, was used, the hemagglutinin exposed at
      the cell surface had to be activated by trypsin, because intracellular cleavage
      was inhibited by this compound. Hemagglutinin mutants resistant to intracellular
      cleavage did not require acidotropic agents for full expression of fusion
      activity, when treated with trypsin after arrival at the cell surface. These
      results indicate that fowl plague virus hemagglutinin expressed by a simian virus
      40 vector is denatured in the acidic milieu of the exocytotic pathway and that
      cleavage is a major factor responsible for the pH instability. Coexpression with
      the M2 protein also markedly enhanced the fusion activity of the hemagglutinin,
      and this effect was inhibited by low doses of amantadine. These results support
      the concept that M2, known to have ion channel function, protects the
      hemagglutinin from denaturation by raising the pH in the exocytotic transport
      system. The data also stress the importance of acidotropic agents or coexpressed
      M2 for the structural and functional integrity of vector-expressed hemagglutinin.

PMID- 8289396
TI  - The cellular polypeptide p57 (pyrimidine tract-binding protein) binds to multiple
      sites in the poliovirus 5' nontranslated region.
AB  - Initiation of translation of poliovirus RNA by ribosomal entry into an internal
      segment of the 742-nucleotide (nt)-long 5' nontranslated region involves trans
      acting factors, including p57, a 57-kDa polypeptide which has been identified as
      the pyrimidine tract-binding protein (PTB). A UV cross-linking assay was used to
      compare the RNA-binding properties of the p57 present in various mammalian
      cytoplasmic extracts with those of purified murine p57 and recombinant human PTB.
      Three noncontiguous p57-binding sites were located within the poliovirus 5'
      nontranslated region, between nt 70 and 288, and 443 and 539 (domain V), and 630
      and 730. With the same assay, a novel 34-kDa polypeptide was identified that
      bound nt 1 to 629 specifically. A single A-->G substitution of nt 480 which
      attenuates poliovirus did not alter UV cross-linking of p57 to domain V. Although
      UV cross-linking of p57 to the internal ribosome entry site was specifically
      reduced by competition with poly(U) but not by competition with poly(C), poly(G),
      and poly(A) homoribopolymers, the presence of a polyuridine tract was not a
      sufficient determinant for binding of RNA to the p57 present in cytoplasmic
      extracts, nor was the polypyrimidine tract downstream of domain V necessary for
      binding to this site.

PMID- 8289397
TI  - Human immunodeficiency virus env expression becomes Rev-independent if the env
      region is not defined as an intron.
AB  - The human immunodeficiency virus (HIV) Rev protein functions to facilitate export
      of intron-containing HIV mRNA from the nucleus to the cytoplasm. We have
      previously shown that splice site recognition plays an important role in Rev
      regulation of HIV env expression. Here we have further analyzed the effects of
      splice sites on HIV env expression and Rev regulation, using a simian virus 40
      late replacement vector system. env expression from the vector became completely
      Rev-independent when an excisable intron was positioned upstream of the env
      region, provided that env was not recognized as an intron. Complete Rev
      regulation was restored either by the insertion of a 5' splice site between the
      intron and the env open reading frame or by deletion of the 3' splice site of the
      upstream intron. These results show that 5' splice sites can function as cis
      acting repressor sequence (CRS) elements to retain RNA in the nucleus in the
      absence of Rev. They also indicate that Rev regulation of HIV env expression is
      critically dependent on whether the env region is defined as an intron. This
      strengthens the hypothesis that Rev interacts with components of the splicing
      machinery to release splicing factors and enable export of the mRNA before
      splicing occurs.

PMID- 8289398
TI  - The effects of cytomegalovirus on human immunodeficiency virus replication in
      brain-derived cells correlate with permissiveness of the cells for each virus.
AB  - Human cytomegalovirus (HCMV) is commonly found in the brains of patients with
      AIDS and in some cases can be detected in the same cells as can human
      immunodeficiency virus type 1 (HIV-1). In this study, we analyzed the patterns of
      replication of HIV-1 and HCMV in singly infected cells and the effects of dual
      infection in human brain-derived cell lines of three different origins:
      neuroblastoma cell lines SK-N-MC and SY5Y; astrocytoma/glioblastoma cell lines
      U373-MG and Hs 683; and undifferentiated glioblastoma cell lines A172 and T98G.
      To bypass the restriction at the adsorption/penetration step in these CD4
      negative cells, we used HIV-1 (amphotropic retrovirus) pseudotypes. These HIV-1
      pseudotypes infected the majority of the cells in the cultures and expressed high
      levels of HIV-1 gene products in all except the SY5Y cells. The cell lines
      differed in the ability to support HCMV infection, but coinfection with HIV-1 had
      no effect on HCMV replication. The A172 cells were completely nonpermissive for
      HCMV gene expression, while HCMV replication in the singly infected T98G and SK-N
      MC cell lines was restricted at the level of some early gene products. This
      resulted in complete and partial inhibition, respectively, of viral DNA
      synthesis. Dual infection of the A172, T98G, and SK-N-MC cells had no effect on
      HIV-1 replication. The other three cell lines, U373-MG, Hs 683, and SY5Y, were
      fully permissive for HCMV replication. In the U373-MG and Hs 683 cells, HCMV
      markedly inhibited the synthesis of HIV-1 gene products. In contrast, a transient
      stimulation of HIV-1 production followed by a repression was observed in the
      dually infected SY5Y cells. We conclude from these results that under conditions
      in which both HIV-1 and HCMV can undergo fully permissive infection, HCMV can
      repress HIV-1 gene expression. In cells in which HCMV replication is limited but
      HIV-1 replicates well, there is no effect on HIV-1 gene expression. However,
      activation of HIV-1, at least transiently, may occur in cells in which HIV-1 gene
      expression is limited. These studies suggest that a threshold level of some HIV-1
      gene product(s) may obscure activation or promote repression of HIV replication
      by HCMV.

PMID- 8289401
TI  - Bioelectrical impedance analysis: a way to assess changes in body cell mass in
      patients with acquired immunodeficiency syndrome?

PMID- 8289399
TI  - Negative-strand RNA transcripts are produced in human immunodeficiency virus type
      1-infected cells and patients by a novel promoter downregulated by Tat.
AB  - Current understanding of human immunodeficiency virus type 1 (HIV-1)
      transcription is based on unidirectional expression of transcripts with positive
      strand polarity from the 5' long terminal repeat. We now report HIV-1 transcripts
      with negative-strand polarity obtained from acutely and chronically infected cell
      lines by use of a template orientation-specific reverse transcriptase-PCR assay.
      These findings were confirmed in natural infection by analysis of RNA derived
      from peripheral blood mononuclear cell samples from 15 HIV-1-infected patients. A
      cDNA derived from a 2.3-kb polyadenylated HIV-1 RNA with negative-strand polarity
      which encodes a highly conserved 189-amino-acid open reading frame antiparallel
      to the envelope gene was isolated from acutely infected A3.01 cells. Through use
      of reporter gene constructions, we further found that a novel negative-strand
      promoter functions within the negative response element of the 3' long terminal
      repeat, which is downregulated by coexpression of Tat. Site-directed mutagenesis
      experiments demonstrated that NF-kappa B I and USF sites are crucial for negative
      strand promoter activity. These data extend the coding capacity of HIV-1 and
      suggest a role for antisense regulation of the viral life cycle.

PMID- 8289400
TI  - RNA polymerase II is aberrantly phosphorylated and localized to viral replication
      compartments following herpes simplex virus infection.
AB  - During lytic infection, herpes simplex virus subverts the host cell RNA
      polymerase II transcription machinery to efficiently express its own genome while
      repressing the expression of most cellular genes. The mechanism by which RNA
      polymerase II is directed to the viral delayed-early and late genes is still
      unresolved. We report here that RNA polymerase II is preferentially localized to
      viral replication compartments early after infection with herpes simplex virus
      type 1. Concurrent with recruitment of RNA polymerase II into viral compartments
      is a rapid and aberrant phosphorylation of the large subunit carboxy-terminal
      domain (CTD). Aberrant phosphorylation of the CTD requires early viral gene
      expression but is not dependent on viral DNA replication or on the formation of
      viral replication compartments. Localization of RNA polymerase II and
      modifications to the CTD may be instrumental in favoring transcription of viral
      genes and repressing specific transcription of cellular genes.

PMID- 8289402
TI  - Total parenteral nutrition with glutamine in bone marrow transplantation and
      other clinical applications.

PMID- 8289403
TI  - Body composition in patients with acquired immunodeficiency syndrome: a
      validation study of bioelectric impedance analysis.
AB  - The objective of this validation study was to explore bioelectric impedance
      analysis (BIA) as a way to assess nutritional status and body composition. The
      study was done in the outpatient department of the AIDS unit at University
      Hospital Dijkzigt, Rotterdam, The Netherlands. Eleven clinically stable patients
      with AIDS were studied. Total body water, body fat, lean body mass, and body cell
      mass were measured and calculated with multiple dilution techniques and BIA. With
      linear regression analysis, a strong correlation was found between total body
      water and lean body mass derived from BIA and multiple dilution techniques (r2 =
      .96 and .98, respectively), and slightly weaker correlation was found for body
      cell mass and body fat (r2 = .88 and .76, respectively). These results suggest
      that BIA is a suitable method for the assessment of body cell mass in HIV
      infected patients without opportunistic infections. The technique is safe,
      noninvasive, fast, and inexpensive.

PMID- 8289404
TI  - Total parenteral nutrition with glutamine in bone marrow transplantation and
      other clinical applications (a randomized, double-blind study)
AB  - In a paper by Ziegler et al (Ann Intern Med 116: 821-828, 1992), total parenteral
      nutrition supplemented with L-glutamine (TPN/GLN) was reported beneficial in
      patients receiving bone marrow transplantation (BMT) for hematologic
      malignancies. By using a similar protocol, we studied 29 patients with both
      hematologic malignancies and solid tumors, and with both allogeneic and
      autologous BMTs. In a double-blind, randomized approach, patients were given
      isocaloric, isonitrogenous TPN after BMT until they consumed 50% of their
      required diet orally. Total body water and extracellular water were measured
      before and after TPN in 10 patients. Total body water increased in patients
      receiving standard TPN and decreased significantly in patients receiving TPN/GLN.
      Length of hospital stay after BMT was significantly (5.8 days) less in patients
      receiving TPN/GLN. Incidence of positive bacterial cultures, clinical infections,
      and mortality did not differ significantly between the two groups. When the
      groups were subdivided into patients with hematologic malignancies and those with
      solid tumors, there were no significant differences in the above variables
      associated with TPN/GLN. In 17 of 30 additional hospitalized patients receiving
      standard TPN, substitution of TPN/GLN did not have discernible clinical or
      laboratory effects but appeared to be safe. Inclusion of patients with solid
      tumors and a higher mortality in our patients may have obscured beneficial
      effects of TPN/GLN observed by others.

PMID- 8289405
TI  - Accuracy of urinary urea nitrogen for predicting total urinary nitrogen in
      thermally injured patients.
AB  - Estimations of total urinary nitrogen from measured urinary urea nitrogen are
      commonly used in calculating nitrogen balance. Recently published studies suggest
      the urinary urea nitrogen/total urinary nitrogen relationship is inconstant and
      total urinary nitrogen must be directly measured in burned patients. This study
      addresses the relationship of urinary urea nitrogen to total urinary nitrogen
      after thermal injury. Two hundred random 24-hour urine collections obtained from
      45 thermally injured patients (mean burn size 59 +/- 28%, mean age 40.5 +/- 17.2
      years) between 1 and 354 days postburn were analyzed for total urinary nitrogen
      and urinary urea nitrogen. Regression analysis relating total urinary nitrogen to
      estimated total urinary nitrogen (urinary urea nitrogen x 1.25) revealed a linear
      relationship (r = .936, p < .001). The mean urinary urea nitrogen/total urinary
      nitrogen ratio was 0.77 +/- 0.10 and was not significantly correlated with
      percent burn, age, or postburn day. Mean nitrogen balance calculated from
      measured urinary urea nitrogen in these patients was -5.7 g, and that calculated
      from measured total urinary nitrogen was -6.3 g. This difference, although
      statistically significant, is of little consequence for clinical use. Contrary to
      recent reports, we found the urinary urea nitrogen to be sufficiently predictive
      of total urinary nitrogen for practical application, and do not consider routine
      total urinary nitrogen measurements necessary for the nutritional care of
      thermally injured patients.

PMID- 8289406
TI  - The effect of total parenteral nutrition on gastrointestinal hormones in rats.
AB  - Total parenteral nutrition (TPN) has been shown to alter the serum concentration
      of certain gastrointestinal hormones. However, the effects of surgical and
      nutritional techniques have not been evaluated adequately. This study examined
      the effects of those techniques on serum gastrin and secretin levels in Fischer
      344 rats fed TPN. After aseptic superior vena cava cannulation and a 4-day
      postoperative recovery period with ad libitum access to food and water, 18 rats
      were randomly and equally (n = 6) assigned to either (1) a baseline group, killed
      after the recovery period; (2) a TPN group fed sufficient nutrients (67%
      dextrose, 21.7% amino acid, 11.3% fat) and kilocalories (1.45 kcal/mL) for normal
      growth and development; or (3) an orally fed (OF) group fed ad libitum a powdered
      diet isocaloric and isonitrogenous to the TPN solution. Both the TPN and OF
      groups were fed for 5 days and then killed. Another set of six rats without
      surgery served as a control (CON) group and had the same diet protocol as the OF
      group. Serum was analyzed for gastrin and secretin by radioimmunoassay. The OF
      group had significantly (p < .01) lower gastrin levels than the CON group.
      Gastrin levels of OF rats were twofold lower (p < .04) than those of the TPN rats
      and were threefold greater (p < .02) than those of the baseline group. Secretin
      levels in OF rats were twice as high (p < .02) as those in CON rats. The OF group
      showed a trend toward significantly (p < .09) higher serum secretin levels when
      compared with the TPN group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289407
TI  - Patients receiving glutamine-supplemented intravenous feedings report an
      improvement in mood.
AB  - Nutritional effects have traditionally focused on outcomes, such as nitrogen
      balance, wound healing, or muscle strength. Little emphasis has been placed on
      how biochemical or physical improvements translate into functional changes as
      perceived by the patient. Because glutamine (GLN)-supplemented nutrition promotes
      protein synthesis and improves nitrogen balance, we assessed the mood of
      individuals participating in a randomized controlled blinded trial receiving GLN
      solutions. Patients (n = 23) undergoing marrow transplantation were randomized by
      the research pharmacist to receive either standard total parenteral nutrition
      (TPN) (control) or GLN-containing TPN (40 g of glutamine total). The solutions
      were isocaloric and isonitrogenous and were administered until the patient was
      eating 50% of estimated requirements. Before TPN and on admission to the
      hospital, the patient completed the Profile of Mood States questionnaire, a
      standardized test quantifying the degree of tension, depression, anger, vigor,
      fatigue, and confusion. The patient completed the questionnaire again at the end
      of TPN near discharge. The tests were scored and the change from baseline for
      each mood for both groups of patients was calculated at the completion of TPN.
      The scores for vigor in the control group (delta scores) decreased over the
      course of hospitalization as would be expected with a serious illness. The group
      receiving glutamine TPN, however, essentially showed little change in vigor from
      baseline and the delta score was significantly different from the control group
      (delta vigor score -0.85 +/- 2.1 in the glutamine group vs. -5.90 +/- 1.7 in the
      control group; p = .07).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289408
TI  - The button jejunostomy for long-term jejunal feeding: results of a prospective
      randomized trial.
AB  - Low profile, self-retaining feeding conduits ("buttons") inserted percutaneously
      through a mature gastrostomy stoma are ideal for prepyloric feeding. We tested
      the efficacy of a surgically inserted button (Button, C.R. Bard, Inc) in the
      jejunum for long-term postpyloric feeding. Forty-two aspiration risk patients
      were prospectively randomized to receive a standard No. 14 French red rubber
      catheter (n = 21, mean age 68 +/- 17 years) or the button (n = 21, mean age 68 +/
      18 years). Common indications for jejunal feeding were aphagia due to
      obtundation (41%) and esophageal dysmotility (41%). All feeding devices were
      inserted 20 cm distal to the ligament of Treitz via a serosal tunnel (catheter)
      or double pursestring (button) technique. No patient required reoperation, and
      cardiopulmonary failure was the most frequent cause of death, occurring in 11
      patients (26%). Goal feedings were obtained in 91% of the catheter patients and
      100% of the button patients by postoperative day 4.7 +/- 1.9 and 4.2 +/- 2.2,
      respectively. At a follow-up of 43 +/- 13 days, 12 (92.3%) of 13 catheter
      patients and 9 (81.8%) of 11 button patients were receiving goal feedings. Three
      patients in the catheter group and four patients in the button group had resumed
      an oral diet. Device-related complications (dislodgment, occlusion, peritubular
      leak, or bowel obstruction) and total number of patients with complications were
      significantly lower in the button group (one [5%] vs eight [38%] for device
      related complications and one [5%] vs six [29%] for incidence of complications
      for the button and catheter groups, respectively).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8289409
TI  - Plasma lipoprotein pattern during long-term home parenteral nutrition with two
      lipid emulsions.
AB  - Hypertriglyceridemia induced by short-term lipid infusions causes redistribution
      of neutral lipid components between endogenous lipoproteins and emulsion
      particles. To determine whether such redistribution occurs over a long-term
      infusion period and affects lipoprotein pattern, we studied seven patients with
      inflammatory bowel disease who received cyclic home parenteral nutrition for two
      consecutive periods of 3 months with two different lipid emulsions. During each
      period, they received in random order either an emulsion composed exclusively of
      soy-derived long-chain triglycerides (LCTs) or another emulsion containing an
      equal weight:weight mixture of long- and medium-chain triglycerides (MCTs/LCTs).
      Both emulsions contained 20 triglycerides (TGs) and 1.2 phospholipids. Lipids
      provided 50 of nonprotein energy. Blood samples were taken once a week, 1 hour
      before the end of infusion (during) and again after a 6- to 8-h lipid-free
      interval (baseline). During infusion, there was a moderate increase of plasma TGs
      and phospholipids and a slight decrease of plasma esterified cholesterol (CE) and
      free cholesterol. Most of the plasma TGs increase occurred in the very-low
      density lipoprotein fraction (containing both emulsion particles and the
      endogenous very-low-density lipoprotein), but there was also an increase of TGs
      content in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) that
      was more pronounced with MCTs/LCTs. Acquisition by exogenous particles of CE
      transferred from LDL and HDL was significant for the LCT emulsion only. Although
      no change was observed in plasma lipid concentration of baseline samples during 3
      months of home parenteral nutrition, some modifications were observed in the
      composition of lipoprotein fractions demonstrating a redistribution of lipid
      components.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289410
TI  - Serious renal impairment is associated with long-term parenteral nutrition.
AB  - Thirty-three current long-term total parenteral nutrition (TPN) patients (13 men,
      20 women) aged 21 to 79 years were prospectively studied to evaluate their change
      in glomerular filtration rate since beginning TPN. Creatinine clearance (CrCl)
      from the subject's initial home TPN clinic visit and at present were estimated
      from standard formulas and compared. The CrCl in 12 patients who had received
      home TPN for > 10 years was estimated retrospectively on a yearly basis. The
      estimated CrCl as an accurate measure of glomerular filtration rate was confirmed
      by measuring plasma indium-111 diethylenetriamine pentaacetic acid clearance. The
      mean daily intravenous protein intake and days during which nephrotoxic
      medications were used and number of bacteremic/fungemic episodes were determined
      for each subject. CrCl declined by 3.5 +/- 6.3% per year (p = .004). Twenty-nine
      of 33 patients had decreases of 0.6% to 15.4% per year. Tubular function, as
      determined by the tubular reabsorption of phosphate, was impaired in 52% of the
      subjects. The intravenous protein load averaged 1.28 +/- 0.32 g/kg per day,
      nephrotoxic drug use averaged 3.4 +/- 4.0% of all days on home TPN, and each
      patient averaged 2.3 episodes of bacteremia or fungemia since home TPN was
      started (0.5 +/- 0.5 episodes per year). When all factors were assessed
      simultaneously, nephrotoxic drug use, episodes of bacteremia/fungemia, and age
      accounted for approximately 46% of the variability in CrCl. When
      bacteremia/fungemia was expressed as a yearly rate, nephrotoxic drug use assumed
      no role in the glomerular filtration rate determination; infection rate and age
      alone accounted for 53% of the CrCl variability. We describe a profound decrease
      in renal function associated with long-term TPN, most of which is largely
      unexplained.

PMID- 8289411
TI  - Nutrition support after total laryngectomy.
AB  - This study was performed to evaluate the influence of different nutrition
      supports (enteral vs parenteral) on nutritional status, postoperative
      complications, and length of hospitalization in patients undergoing total
      laryngectomy. Forty-eight patients were divided at random into two groups and
      received enteral nutrition support by percutaneous endoscopic gastrostomy with a
      casein and soy-based polymeric formula blended with a modular protein (group A)
      or a balanced formula in total parenteral nutrition given through a subclavian
      venous catheter (group B). The results show a satisfactory preservation of
      nutritional status after total laryngectomy and no significant differences in the
      nutritional parameters between groups fed enterally or parenterally; however,
      percutaneous endoscopic gastrostomy could avoid many problems related to enteral
      nutrition support for patients undergoing laryngectomy. This route of
      administration was well tolerated by all the patients and, moreover, the
      percutaneous endoscopic gastrostomy-related complications were clinically less
      significant than those associated with total parenteral nutrition; this fact
      could explain the longer hospitalization for group B (34 +/- 11 vs 26 +/- 11
      days) (p < .05).

PMID- 8289412
TI  - Hepatobiliary complications in healthy, intra-abdominally infected, and high
      output fistula rats receiving total parenteral nutrition.
AB  - This study examines the pathophysiology of hepatobiliary complications induced by
      total parenteral nutrition (TPN) by using animal models that underwent cecal
      ligation to produce intra-abdominal infection and received an enterostomy to
      mimic a high-output fistula, which causes the interruption of enterohepatic
      circulation of bile salt. Aspartate transaminase was elevated after TPN (p <
      .05). Alkaline phosphatase was increased in animals receiving TPN plus an
      enterostomy (p < .05). Serum albumin was significantly decreased in animals
      receiving TPN plus undergoing cecal ligation or enterostomy (p < .05). Liver
      weight and liver protein and water content decreased in animals receiving TPN
      alone (p < .05). Liver water content increased in animals receiving TPN plus
      undergoing cecal ligation (p < .05). Liver lipid content increased after TPN and
      to a significant degree in rats receiving TPN plus undergoing cecal ligation or
      enterostomy (p < .05). Bile flow diminished after TPN and to a level reaching
      significance in animals receiving TPN plus undergoing cecal ligation or
      enterostomy (p < .05). Reduction of bile flow, decrease of biliary cholesterol
      secretion, and increase of biliary bilirubin secretion, which may be the cause of
      TPN-induced bilirubinate stones, were most significant in animals receiving TPN
      plus undergoing cecal ligation (p < .05). In conclusion, TPN can induce hepatic
      dysfunction and bilirubinate stones, but these complications are more common in
      animals with associated intra-abdominal infection or high-output fistula.

PMID- 8289413
TI  - A study of the delayed hypersensitivity response in healthy people in Spain:
      Spanish National Tables. National Surgical Infection Committee of the Association
      of Spanish Surgeons.
AB  - With a view to creating national tables of the delayed hypersensitivity response,
      a total of 1476 healthy persons were studied at eight different locations in
      Spain. For the measurement of delayed cellular immunity response, Multitest IMC
      was used. Of those examined, 0.7% were anergic, 21.3 were relatively anergic, and
      73 were immunocompetent. Of the 766 men, 28 were relatively anergic and 3 were
      anergic, whereas of the 710 women, 14 were relatively anergic (p < .001) and 8%
      were anergic (p < .001). The highest incidence of anergy was found in women of
      over 70 years (p < .001). Tuberculin was the antigen with the most positive
      responses, 77%, followed by Candida with 58%. Trichophyton and Proteus mirabilis
      were the antigens least recognized by the Spaniards studied. Major geographical
      variations were observed, both in the overall index for the delayed
      hypersensitivity response and in the response to different antigens. Catalonia
      revealed the highest level of anergy and the Valencia region, the lowest.

PMID- 8289415
TI  - Contamination of a prefilled ready-to-use enteral feeding system compared with a
      refillable bag.
AB  - The contamination of a refillable bag enteral feeding system was compared with a
      prefilled, ready-to-use system on four stable patients with gastrostomies in a
      longterm care facility. Samples were taken from the distal end of the tubing
      attached to the formula reservoir three times (just before administration to the
      patient, during the morning medication pass, and just before the reservoir
      change) during 24 hours for 3 days with use of the refillable bag, the ready-to
      use system, and the ready-to-use system with a Y-port added. A Y-port was added
      to the ready-to-use system to facilitate administration of water, medications,
      residual checks, and specimen collection without disconnection of the gastrostomy
      tube from the formula reservoir tubing when it was apparent that the
      contamination levels of the refillable bag and the ready-to-use system were not
      different. Forty-one (65%) of the 63 specimens collected while the Y-port was not
      being used exceeded the acceptable contamination level for grade A pasteurized
      milk. Five (28%) of the 18 specimens collected while the Y-port was in use
      exceeded this level. Use of a Y-port is suggested when a prefilled ready-to-use
      system is used to decrease contamination as well as save nursing time.

PMID- 8289414
TI  - Adhesion of percutaneously inserted Silastic central venous lines to the vein
      wall associated with Malassezia furfur infection.
AB  - Percutaneously inserted Silastic central venous catheters have been used for
      prolonged infusion of parenteral nutrition in neonates. Malassezia furfur
      infection has been associated with intravenous fat emulsions infused through
      central venous lines. In this paper, we report two premature infants whose
      Silastic catheters were adhered to the vein wall with associated M furfur
      infection.

PMID- 8289416
TI  - Serum vitamin K concentration in pediatric patients receiving total parenteral
      nutrition.
AB  - The only multivitamin preparation for total parenteral nutrition currently
      available in the United States that contains vitamin K is the pediatric
      formulation MVI-Pediatric. The recommended dose provides 200 micrograms of
      vitamin K1 per day to term infants and children up to 11 years old. This dose is
      well above the recommended dietary allowance of approximately 1 microgram/kg per
      day, but the losses of vitamin K during administration are unknown. We evaluated
      the stability of vitamin K1 in a standard total parenteral nutrition infusion and
      found that an average 72.7 +/- 4.9% of the original vitamin K1 was present after
      24 hours. By using high-performance liquid chromatography with electrochemical
      reduction and fluorescence detection, we obtained the serum vitamin K1
      concentrations in 11 pediatric patients receiving total parenteral nutrition with
      MVI-Pediatric (Rorer Pharmaceuticals, Fort Washington, PA) supplementation and in
      control children. The serum vitamin K1 concentration (19.3 +/- 12.2 ng/mL) in
      patients receiving MVI-Pediatric is significantly higher than that in control
      children 1.9 +/- 1.5 ng/mL (p < .001). Current practice results in excessive
      levels of vitamin K in pediatric patients.

PMID- 8289417
TI  - First choice for total parenteral nutrition: the peripheral route.
AB  - Historically, total parenteral nutrition (TPN) has been administered by the
      central venous route because of the rapid development of thrombophlebitis when
      TPN solutions are administered into peripheral veins. The insertion and placement
      of central venous catheters is, however, associated with morbidity and mortality
      and is the main cause of TPN-related complications. By avoiding central venous
      catheterization, TPN can be made safer. Current awareness about the
      pathophysiology of peripheral vein thrombophlebitis and the use of a number of
      techniques that prevent or delay onset of peripheral vein thrombophlebitis mean
      it is now possible to administer TPN via the peripheral route. These techniques
      and changes in the practice of TPN in recent years (eg, reduction of caloric
      loads and use of lipid emulsions) mean peripheral parenteral nutrition is a
      technique that is now applicable to the majority of hospitalized, nutritionally
      compromised patients for whom intravenous feeding is anticipated for less than 10
      to 14 days.

PMID- 8289418
TI  - A new technique for placement of central venous catheters in small infants.
AB  - The delivery of total parenteral nutrition to premature infants has been a major
      advance in neonatal intensive care. Ideally, total parenteral nutrition fluids
      should be given through a central venous catheter, but insertion of such a
      catheter may be a very difficult procedure in small neonates. We describe a new
      technique that improves the success rate of central venous catheterization in
      premature infants.

PMID- 8289419
TI  - A comparison of medium-chain and long-chain triglycerides in surgical patients.

PMID- 8289420
TI  - Early changes of body composition in human immunodeficiency virus-infected
      patients: tetrapolar body impedance analysis indicates significant malnutrition.

PMID- 8289421
TI  - A simple technique to redirect malpositioned Silastic central venous catheters.

PMID- 8289422
TI  - Fifteen-year survival of a Broviac catheter used for home parenteral nutrition.

PMID- 8289423
TI  - Peripheral parenteral nutrition: a preliminary report on its efficacy and safety.

PMID- 8289424
TI  - Hospital staff privileges and liability.

PMID- 8289425
TI  - A core electronic medical library in a rural setting: update.
AB  - In rural areas an electronic medical library is one of the most effective ways of
      staying abreast of advances in clinical medicine. A health care provider's
      educational needs for staying current are best met by a combination of CD-based
      textbooks and an inexpensive on-line database. Since publication of this review
      last year, several beneficial changes have occurred. In general, they are:
      greater availability of fast data transmission rates, wider selection of
      databases to choose from, both on-line and off-line, the feasibility of obtaining
      toll-free access numbers in selected instances, and the elimination of daytime
      higher connect rates. This update discusses some of these changes.

PMID- 8289426
TI  - Rural health manpower issues affecting older Kansans.

PMID- 8289427
TI  - Disseminated cryptococcosis with hypothyroidism in an AIDS patient.

PMID- 8289428
TI  - Outbreak of pneumococcal disease in a Kansas nursing home, 1993.

PMID- 8289429
TI  - [Surgical treatment for mitral valve defects with preponderance of mitral
      stenosis and high pulmonary vascular resistance. Clinical and hemodynamic
      observations 6 months after valve replacement].
AB  - 10 patients with isolated or predominant mitral stenosis (mean mitral valve area
      0.9 cm) and high preoperative values of pulmonary vascular resistance (mean 7.2
      Wood units) were chosen for further hemodynamic postoperation evaluation. The
      patients had normal function of the aortic valve and no significant stenosis of
      coronary arteries. Hemodynamic evaluation was done by floating Swan-Ganz catheter
      preoperatively at rest and 6 months after mitral valve replacement at rest and
      during bicycle cycloergometer test in the supine position. Significant
      improvement in NYHA class was noted. Preoperatively 6 patients were in NYHA III
      class, 4 in NYHA IV class. After mitral valve replacement 4 patients were in
      class III and 6 in class II. Before mitral valve replacement only 3 patients were
      able to perform 25 Watt test. After surgery all except one performed at least 25
      W. There was a significant decrease of pulmonary vascular resistance from 7.2 +/-
      2.2 preoperatively to 3.1 +/- 1.9 Wood units at rest after the operation. Post
      operation during exercise pulmonary vascular resistance attained 4.2 +/- 1.9 Wood
      units. These changes were due to a fall in mean pulmonary artery pressure 49 +/-
      13 at rest preoperatively to 25 +/- 6 mm Hg (rest) and 43 +/- 14 mm Hg (23 W)
      postoperatively and a rise in stroke volume index from 24 +/- 7 ml (m2) beat
      preoperatively to 32 +/- 9 at rest and 33 +/- 6 (25 W) postoperatively. Despite
      clinical and hemodynamic improvement there was no full recovery of pulmonary
      hemodynamics.

PMID- 8289430
TI  - [Cardiomyopathy in diabetes. Ultrastructural examinations].
AB  - The functional and morphological changes in myocardium of diabetic patients is
      caused by diabetic macroangiopathy, diabetic microangiopathy, autonomic
      neuropathy and metabolic disorders. Mechanism of these changes in the course of
      diabetes is not fully known. To determine whether there are myocardial
      ultrastructure differences between patients with diabetic cardiomyopathy (normal
      coronary angiograms) and diabetic patients with coronary artery disease, electron
      microscopy examination were performed of 70 sections received from seven biopsied
      patients (1F, 6M), average age 53 years (range: 42-60) with diabetes type II WHO
      (group A) without clinical evidence of prior coronary artery disease and
      hypertension, and 100 sections from 10 patients (2F, 8M), average age 54 years
      (range: 42-65) with diabetes and coronary atherosclerosis. These patients had
      clinical evidence of heart failure and were submitted to bypass-graft operations
      (group B). Endomyocardial biopsy tissues were obtained from the right ventricle
      without complications either during or after the procedure. Obtained biopsy
      specimens were fixed in 3% glutaraldehyde stabilized with 1M cacodylate buffer at
      pH 7.4, postfixed in 1% OsO4 on cacodylate buffer. The materials were then
      dehydrated and embedded in epon. The Irvin-Fischer test for statistical analysis
      was used. A p value < 0.05 was considered significant. The presence of focal mild
      loss of myofibrils (+) was statistically more frequent in the patients in A group
      (p < 0.05). It was found in 86% (6/7) of cases in A group, while in the B group
      was observed in 20% of (2/10) cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289431
TI  - [Left ventricular stroke volume in individuals with dual chamber pacemaker (DDD).
      Effect of atrioventricular delay].
AB  - Programming of atrioventricular delay in patients with dual chamber pacemaker is
      very important for left ventricular filling and has a consequence for its stroke
      volume. The aim of this study was to evaluate the influence of atrioventricular
      delay for left ventricular stroke volume during pacing at two different rates.
      The study was performed in 36 patients with DDD pacemaker aged from 30 to 81
      years, mean 56.1 +/- 14.6. Using Doppler echocardiography we have assessed left
      ventricular stroke volume during two pacing rates (70 and 100 ppm) with four
      atrioventricular delays (100, 150, 200 and 250 ms). We have found statistically
      significant difference between stroke volume with various atrioventricular
      delays. During pacing rate of 70 ppm the maximal difference was 19% and 15%
      during 100 ppm. Comparing both pacing rates the distributions of hemodynamically
      optimal atrioventricular delays was also significantly different. The best
      atrioventricular delay from the hemodynamic point of view was 36 ms longer during
      70 ppm of pacing rate than during 100 ppm (p = 0.0009). The most often optimal
      delay at 70 ppm was 190-200 ms, and the rarest optimal delay was 90-100 ms;
      during 100 ppm pacing respectively: 140-150 ms and 240-250 ms. We have observed
      considerable personal variability in the hemodynamic response for
      atrioventricular delay changing as well as in the hemodynamically optimal values
      of this parameter during both pacing rates. CONCLUSIONS: 1. Atrioventricular
      delay programming has significant influence on left ventricular stroke volume. 2.
      Programming of atrioventricular delay should be performed individually in every
      patient because of personal variability of optimal values of this
      parameter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289432
TI  - [Multi-plane transesophageal echocardiography--the next step to 3 dimensional
      imaging of the heart].
AB  - The multiplane transesophageal echocardiography (MTEE) is a new method making the
      precise imaging of the heart and great vessels possible. That technique allows to
      obtain the images of cardiovascular structures in two perpendicular investigation
      planes ("biplane" operation): transverse (examination angle is equal to 90
      degrees--in relation to long axis of esophagus) and longitudinal = sagittal
      (examination angle is equal to 0 degree--in relation to long axis of esophagus)
      and, as well, in all medial planes enclosed from 0 degree to 90 degrees
      examination angle. During the investigation planes were being rotated
      mechanically or manually by rotation wheel. Passing from one plane to another is
      fluent, due to that the heart and main vessels can be observed continuously.
      Sector angle variability is 180 degrees (from minus 90 degrees to plus 90
      degrees). The investigation planes from 0 degrees to plus 90 degrees from so
      called "normal" visualization field, and planes from 90 degrees to 0 degree make
      a "mirror" reflection of the "normal" field (mirror field). In our investigations
      the Vingmed-Sonotron echocardiograph connected with 5 MHz annular phased--array
      transducer, placed at the end of flexible endoscope was used. The multiplanar
      transducers have a full Doppler option (pulsed and continuous waves) with the
      possibility of colour flow imaging. The initial experience with the new method is
      presented in this report. The MTEE enables precise assessment of atrial septal
      defects. The multiplane imaging allows complete evaluation of heart muscle
      thickness and left ventricular contractility. This technique gives a better
      visualization of coronary artery. MTEE permits for planimetric assessment of
      aortic valve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289433
TI  - [Decrease in the level of free cholesterol fraction HDL as a risk factor for
      threatened atherosclerosis in idiopathic hyperinsulinemia].
AB  - Inversive association between concentration of plasma high density lipoprotein
      (HDL) components and endogenous insulin response to oral glucose uptake was
      observed in 89 healthy, normolipidaemic, non obese, non diabetic male subjects.
      Inversive correlation between sum of insulin released during oral glucose
      tolerance test and HDL free and esterified cholesterol as well as apolipoprotein
      A1 concentration were confirmed. Coexistence of increased insulin secretion and
      low ratio of free cholesterol concentration to esterified cholesterol and to
      proteins in HDL was also observed. In separate group of subjects with normal
      glucose tolerance in high insulin response subgroup the cholesterol (free and
      esterified) and protein concentrations were lower than in subgroup with low
      insulin response. The free cholesterol/esterified cholesterol and free
      cholesterol/protein (apoA1) ratios were decreased in high insulin response
      subgroup. It is concluded that low concentration of free cholesterol is a most
      significant change of HDL composition in hyperinsulinemic, healthy men.

PMID- 8289434
TI  - [Familial dilated cardiomyopathy with autosomal mode of inheritance. Case
      report].
AB  - Familial occurrence of dilated cardiomyopathy is estimated by 2-20%. We present a
      family with dilated cardiomyopathy inherited in an autosomal dominant way. We
      examined 9 members of the family, most of them are asymptomatic.

PMID- 8289435
TI  - [Diagnosis of perioperative myocardial infarction during coronary artery bypass
      surgery].

PMID- 8289436
TI  - A case of benign schwannoma of the thoracic wall mimicking a malignant tumor.
AB  - A fist-sized tumor mainly locating in the right thoracic wall of a 73 year-old
      woman was found by ultrasonography and computed tomography, although a definitive
      diagnosis was not obtained because of the tumor extension to the abdominal cavity
      from the right internal thoracic wall, precluding biopsy. Angiography of the
      right eleventh intercostal artery demonstrated irregular tumor vessels,
      indicating malignant nature of the tumor. Therefore en-block resection of the
      tumor with the right eleventh rib was performed under a thoracotomy.
      Postoperative histopathological examination showed that the tumor was a benign
      schwannoma of Antoni type A. Since schwannoma is usually difficult to diagnose
      preoperatively without histopathological study, it is suggested that patients
      with schwannoma-like tumors, as represented by the present case, should be
      treated carefully to avoid excessive surgery including an extensive resection of
      the surrounding tissue.

PMID- 8289437
TI  - Infantile neuroaxonal dystrophy--immunohistochemical and ultrastructural studies
      on the central and peripheral nervous systems in infantile neuroaxonal dystrophy.
AB  - We performed pathological studies on the central and peripheral nervous systems
      of cases with infantile neuroaxonal dystrophy (INAD). Numerous spheroid bodies in
      the central and peripheral nervous systems, were seen and divided into large
      spheroid bodies (LSB) and small spheroid bodies (SSB) photo-microscopically. LSB
      had a relation to some specific neurons with weak expression of neuron specific
      enolase, neurofilament and chromogranin using PAP method. SSB showed a relation
      to the axon without immunohistochemical expression of neuron specific enolase,
      neurofilament, glial fibrillary acidic protein, myelin basic protein,
      chromogranin, S 100 protein or antitrypsin. LSB were prominent in the posterior
      column, gracile nucleus, cuneate nucleus, and the tegmentum of the midbrain and
      the pons associated with neuronal loss and gliosis. SSB were observed in the
      thalamus, basal ganglia and the cerebral cortex. The cerebellum was sclerotic
      with few microtubule-like structures disposed in a dense network in association
      with degenerated mitochondria. Similar changes were observed in the sural nerves,
      autonomic nerve endings in the skin, and the nerve plexus of the digestive tract.
      Although INAD is a generalized neurodegenerative disease, it is suggested that
      the primary disorder might occur in the neurons and axons of the sensory tracts.

PMID- 8289438
TI  - Guidelines for working with students having special health care needs.
AB  - Students with special health care needs present challenges to persons involved
      with their education, but school staff are accepting the challenge to create
      safe, nurturing, and stimulating environments for these students. This article
      proposes guidelines for school staff working with students having special health
      care needs. The guidelines evolved from the authors' experiences and are child
      related, family-related, and school-related. Discussion of each guideline
      includes illustrations of issues arising from them. Considerations for
      implementing the guidelines are presented and include discussion of school
      policies and procedures and state laws and regulations related to school staff
      working with students having special health care needs.

PMID- 8289439
TI  - The linkage approach applied to a school-based smoking prevention program in The
      Netherlands.
AB  - Effective diffusion strategies are necessary to enhance use of innovative health
      promotion programs. One strategy uses the linkage approach to innovation
      development and diffusion planning. The linkage approach enhances collaboration
      among three systems: resource system (university-based researchers), linkage
      system (district health educators), and user system (teachers). This article
      illustrates how the linkage approach was applied in a smoking prevention research
      project. Identification of the linkage system and the collaborative process
      between the resource system and linkage system are described. Results from a
      process evaluation indicated the linkage approach was feasible in a school-based
      smoking prevention project.

PMID- 8289440
TI  - Dissemination and use of a school-based nutrition education program for secondary
      school students.
AB  - Program dissemination and implementation represent critical components of
      effective school-based health promotion interventions. This study examined the
      dissemination and implementation of a nutrition teaching program, Nutrition For
      Life, in New York State secondary schools. Some 1,312 health, home economics, and
      physical education teachers in junior and senior high schools provided
      information through random sample mail surveys. Logistic regression procedures
      examined teacher and school characteristics associated with receipt and use of
      the program. Overall, 50% of junior high school and 33% of senior high school
      teachers received the program and three-quarters of these teachers used it. At
      both levels, home economics teachers were more likely to receive and use the
      program than health teachers. Peer-led teacher training workshops organized
      through an existing community-based network provide an effective and efficient
      mechanism for disseminating nutrition teaching programs.

PMID- 8289441
TI  - Teachers' use of health curricula: implementation of growing healthy, project
      SMART, and the teenage health teaching modules.
AB  - This quasi-experimental study assessed impact of factors associated with
      classroom implementation of health curricula by North Carolina teachers. School
      representatives selected and implemented one of three tobacco prevention
      curricula--Project SMART, Growing Healthy, or the Teenage Health Teaching Modules
      -in either sixth or seventh grades. Prior to implementation, experimental
      teachers and administrators received extensive curricula training. Implementation
      data were collected through teacher completed checksheets and classroom
      observations for two time periods--initial implementation (n = 69) and maintained
      implementation (n = 136). While training was associated significantly with
      whether teachers implemented a curriculum (p < .05), other factors also were
      important. Variables outside of teachers' direct control, such as supportive
      administrators, context in which health instruction is taught, and turbulence,
      affected quantity and quality of curricular implementation.

PMID- 8289442
TI  - Hostile hallways: the AAUW survey on sexual harassment in America's schools.
      American Association of University Women.

PMID- 8289443
TI  - Student views of the school nurse's role in a secondary school condom
      availability program.

PMID- 8289444
TI  - The role of a cancer center in a private community hospital.

PMID- 8289445
TI  - Morbidity of radical retropubic prostatectomy following previous prostate
      resection.
AB  - A total of 153 patients with prior prostate surgery underwent a radical
      retropubic prostatectomy for carcinoma of the prostate. Ninety-seven patients had
      undergone transurethral resection of the prostate (TURP), and 56 patients had
      undergone suprapubic transvesical prostatectomy (SPP). In 115 patients, the
      diagnosis of malignancy was made at the time of transurethral resection or
      enucleation. No perioperative deaths occurred and no patient suffered rectal
      injury or ureteral transection. Operative time and blood loss were similar
      between the TURP and SPP groups and were not different in a group of patients who
      had not had prior prostate surgery. Early and late complications occurred in
      eight patients (5.2%), of whom seven had had previous TURP. Complete urinary
      control was achieved in 96% (147) of the patients; stress incontinence was
      present in 4% (6 patients); and no patient was totally incontinent. Postoperative
      complications and the occurrence of stress incontinence were not related to the
      time elapsed between the previous prostate surgery and the radical prostatectomy.
      Sexual function was preserved in 32 (71%) of the 45 patients in whom we performed
      a nerve-sparing radical prostatectomy. Residual cancer was found in the radical
      prostatectomy specimen in 77 (67%) of the stage A patients. Twenty-nine (25%) of
      the stage A and 13 (34%) of the stage B patients had pathological evidence of
      disease extension beyond the confined prostate. Follow-up was 6-92 months, with a
      mean of 32 months. Four patients died of prostatic cancer, two patients died
      without cancer, and five have evidence of disease progression; 142 (93%) are
      alive without evidence of disease. Although radical prostatectomy sometimes is
      more difficult after previous prostate surgery, operative complication rates,
      patient morbidity, and the opportunity for surgical cure are not different from
      those seen in patients with no history of previous prostate operations.

PMID- 8289446
TI  - The role of suprahyoid block dissection in carcinoma of the floor of the mouth.
AB  - The efficacy of suprahyoid block dissection combined with radiotherapy, in the
      management of neck nodal disease was evaluated in 15 patients with carcinoma of
      the floor of mouth (abutting on the mandible) between 1983 and 1989. Ten males
      and 5 females had a mean age of 60.3 years. Suprahyoid block dissection was
      performed in 10 patients as initial treatment. Nine of these presented with a
      submandibular mass and one patient with a T4NO lesion had a prophylactic block
      performed. Suprahyoid block dissection was performed in five patients who
      developed a submandibular mass after completion of surgery and radiotherapy.
      Wound sepsis occurred in three patients, but resolved with conservative
      treatment. Clinical assessment of the suprahyoid mass was accurate in 65% of
      patients. Nodal recurrence occurred in one patient. Seven patients are alive and
      disease free after a mean of 64.5 months. Two other patients are alive, one with
      lung metastases, and one with a supraclavicular mass. Six patients have died, two
      of whom developed local recurrence, one who developed a supraclavicular mass, one
      after nodal recurrence, one with lung metastases, and one of an unrelated cause.
      Suprahyoid block dissection combined with radiotherapy is effective treatment for
      nodal control of patients with carcinoma of the floor of mouth. This procedure is
      associated with a low morbidity.

PMID- 8289447
TI  - Technique for the management of Santorini's deep venous plexus during radical
      retropubic prostatectomy.

PMID- 8289448
TI  - The regional treatment of liver metastases from breast cancer.
AB  - To determine the effect of aggressive regional therapy for liver metastasis from
      breast cancer, we retrospectively reviewed data on 74 patients identified with
      liver metastases. Forty had only liver metastases. In this group of 40 patients,
      18 were treated with regional therapy only, i.e., surgical resection and/or
      regional chemotherapy via hepatic artery or portal vein catheters whereas 22
      patients had systemic chemotherapy. The two groups were comparable. The regional
      chemotherapy regimen was 5-FU, Adriamycin, methotrexate, and cytoxan. Median
      survival (27 months) for those patients treated with regional therapy (N = 18)
      was significantly longer than for those (N = 22) treated with systemic therapy (5
      months) (P = 0.001). Only 45% of the regional treatment group failed in the
      liver. Our data, although retrospective and selective, suggest that certain
      subgroups of breast cancer patients with metastatic liver disease may benefit
      from aggressive regional therapy.

PMID- 8289449
TI  - Gastric cancer in young adults: growth accelerating effect of pregnancy and
      delivery.
AB  - The relationship between pregnancy and/or delivery (p&d) and the stage of gastric
      cancer was studied in 64 female and 57 male patients aged 34 or younger with
      gastric cancer. Gastric cancer diagnosed within 2 years after p&d (group A, 20
      patients) was more progressive (unresectable in 20%) than those of the other
      young female patients with children (group B, 24 patients; 5%) or without
      children (group C, 20; 0%), or young male patients (group D, 57; 3%) (P < 0.05).
      The 5-year survival rate in group A (60.0%) was lower than in group B (83.3%) and
      group C (85.0%) (P < 0.05 between groups A and B). There were no differences in
      the duration from the onset of subjective symptoms to diagnosis in the four
      groups. Out of eight patients who were pregnant after gastrectomy for stomach
      cancer, one died from recurrence immediately after abortion. These results
      suggest that pregnancy and/or delivery in young females accelerates the growth of
      stomach cancer.

PMID- 8289450
TI  - Nutritional support and prognosis in patients with head and neck cancer.
AB  - We retrospectively studied the relationship between nutritional status as
      indicated by the presence or absence of the cutaneous delayed hypersensitivity
      response and treatment-related morbidity, disease recurrence, and survival at 2
      years in 67 consecutive patients with head and neck carcinoma. Serial nutritional
      assessments were conducted throughout the course of combined initial
      antineoplastic treatment and nutritional support. The presence of cell-mediated
      immunity at the end of treatment was associated with a 2-year survival rate of
      100%, whereas patients who were anergic at the end of treatment had a 2-year
      survival rate of 48% (P < 0.01). Morbidity due to surgical therapy and tumor
      recurrence rates were also higher in the anergic group (P < 0.01). Prognosis in
      head and neck cancer is based on many factors, but vigorous nutritional support
      during initial treatment may have some effect on morbidity, tumor recurrence, and
      survival time.

PMID- 8289451
TI  - Survival differences between black and white women with breast cancer.
AB  - Several reports have indicated that black women with breast cancer have a poorer
      prognosis than white women. To investigate this phenomenon and to identify some
      of the underlying reasons, 172 patients with infiltrating ductal carcinoma of the
      breast, who were managed similarly, were studied. Survival analysis comparing the
      two populations with breast cancer revealed that white women had significantly
      longer overall survival (OS), P = 0.015 by Wilcoxon and 0.019 by log-rank, and
      borderline significantly longer disease-free survival (DFS), P = 0.04 by Wilcoxon
      and 0.07 by log-rank. While there was no significant difference in OS and DFS
      between the two groups with negative nodes, significantly poorer DFS and OS was
      noted in black patients with one to three positive lymph nodes compared to white
      patients, P = 0.008. The white patients had a higher incidence of hormone
      receptor-positive tumors, especially progesterone receptor (P = 0.0016). However,
      survival analysis failed to show any difference between the black and the white
      populations based on hormonal receptors. Such findings suggested that further
      investigation of other factor(s) is warranted.

PMID- 8289452
TI  - Selective digital enhancement of conventional film mammography.
AB  - Screening mammography continues to play a key role in the early diagnosis of non
      palpable breast cancer. Approximately 5% of patients will have lesions on their
      mammograms that appear neither clearly benign nor malignant. The proper
      management of these patients is not well defined. In this study, the mammograms
      of 64 women who underwent breast biopsy were reviewed. After the initial review,
      the mammograms were reevaluated using a personal computer driven digital
      conversion and enhancement system. The majority of indeterminate lesions were
      assigned a determinate diagnosis by enhancing the areas of abnormality through
      enlargement, contrast adjustment, and brightness adjustment. The radiologists
      were able to maintain baseline sensitivity and specificity throughout this
      process. In contrast, enhancement of lesions initially assigned a diagnosis of
      characteristically benign or malignant demonstrated no advantage over plain film
      mammography. These findings suggest a role for the selective use of digital
      mammography and enhancement techniques.

PMID- 8289453
TI  - Integrated approach to the management of patients with advanced germ cell tumors
      of the testis.
AB  - Between 1985 and 1991, 63 patients with disseminated germ cell tumors of the
      testis were treated with initial cisplatin based combination chemotherapy.
      Complete response was seen in 38% of patients. Adjunctive surgical resection of
      residual disease was carried out in 26 patients (41%), including the use of
      intraoperative radiation therapy in two patients with seminoma. Furthermore, two
      other patients with seminoma and residual mass underwent retroperitoneal
      irradiation. Salvage chemotherapy was administered to five patients with
      progressive disease, and only one of these could be salvaged with adjunctive
      surgery. A disease-free state was achieved in 75% of patients at a mean follow-up
      period of 30 months.

PMID- 8289454
TI  - The effect of sulindac on colon polyps: circumvention of a transformed phenotype-
      a hypothesis.
AB  - Sulindac suppresses the growth of colon polyps in Gardner syndrome and familial
      adenomatous polyposis. The mechanism of action is not known. The problems are to
      ascertain the significance of high prostaglandin concentrations in transformed
      cells, colon polyps and cancers and to explain how sulindac restores normal
      growth patterns. A few clinical observations and an abundance of experimental
      data can be integrated to produce a reasonable model based on current biochemical
      and physiologic concepts. A fundamental defect in the formation of colon polyps
      is mutation of the APC (adenomatous polyposis coli) gene that leads to inadequate
      suppression of proliferation. There is high PGE2 content in colon polyps and
      cancers, presumably the result of stimulation by protein kinase C (PKC). In small
      quantities it stimulates cyclic AMP production but with persistent high
      concentrations it desensitizes and down-regulates specific PG receptors and
      inactivates adenylate cyclase, cAMP synthesis, and the cAMP-dependent mechanism
      for control of proliferation. The PKC pathway is thereby unopposed. It is
      hypothesized that restriction of PG synthesis by sulindac is accompanied by
      resensitization of PG receptors, and reactivation of the cAMP-dependent pathway
      for control of cell growth. It is further postulated that restoration of cAMP
      synthesis and protein kinase A activity converts a functionally inadequate mutant
      APC suppressor gene to one sufficient to inhibit colon polyp formation.

PMID- 8289455
TI  - Growing teratoma syndrome.
AB  - Growing teratoma syndrome is the term applied to enlarging retroperitoneal or
      other metastatic masses containing mature teratoma during chemotherapy for
      nonseminomatous germ cell tumors. Four cases of the growing teratoma syndrome are
      presented, the metastatic masses being in the retroperitoneal in all the cases.
      All these patients had enlarging retroperitoneal masses in the presence of normal
      serum biomarkers following chemotherapy for nonseminomatous tumors. Surgical
      excision was carried out in all four patients, with disease free survivals
      ranging from 6 to 24 months after surgery.

PMID- 8289456
TI  - Rapidly growing thyroid carcinoma during pregnancy.
AB  - We experienced two cases of papillary carcinoma of the thyroid during pregnancy.
      The thyroid carcinomas grew rapidly in early pregnancy. We speculate that human
      chorionic gonadotropin plays an important role in the rapid growth of thyroid
      carcinoma during pregnancy.

PMID- 8289457
TI  - Melanotic neuroectodermal tumor of infancy: report of a case with ganglionic
      differentiation.
AB  - Melanotic neuroectodermal tumor of infancy (MNTI) is a rare but well-documented
      lesion of neuroectodermal derivation. Maturation of the neural elements has been
      reported only occasionally. We report a case of MNTI of the maxilla showing
      maturation of neural elements to ganglionic cells.

PMID- 8289458
TI  - Nephrectomy for metastatic renal cell carcinoma: a component of systemic
      treatment regimens.
AB  - New immunotherapeutic and chemotherapeutic regimens have altered the medical
      approach to metastatic renal cell carcinoma (RCC). Surgery for metastatic RCC
      needs to be reappraised in the context of these developments. We retrospectively
      examined the course of 25 patients with metastatic RCC who underwent nephrectomy
      or resection of renal fossa recurrences as an adjunct to intended systemic
      therapy. Four patients (16%) had complications and there was no perioperative
      mortality. Of 23 patients who had surgery first, 17 received subsequent systemic
      therapy and 2 experienced a response. Two patients underwent nephrectomy after
      achieving a partial response with systemic therapy. Overall, 3 patients (12%) are
      alive without detectable disease, 8 (32%) are alive with disease, and 14 (56%)
      are dead of disease, with a median survival of 23.5 months. Nephrectomy for
      metastatic renal cell carcinoma may be associated with less morbidity and
      mortality than previously reported. When initial nephrectomy is performed, most
      patients go on to receive systemic therapy. Within the context of a systemic
      treatment regimen, nephrectomy continues to play a role in the management of
      selected patients with metastatic RCC.

PMID- 8289459
TI  - A unified model of immune response. II: Continuum approach.
AB  - In an earlier paper in this journal (1990, J. theor. Biol. 145, 207-215) we
      developed a unified model for normal immune response, autoimmune response and
      AIDS, where the concentration of each type of cell involved in the immune
      response is represented by a discrete automaton and the population dynamics of
      the relevant cells are formulated in terms of dynamical maps in discrete time. In
      this paper we study the continuum version of this unified model where the cell
      concentrations are represented by real variables whose evolution with continuous
      time is described by differential equations. We discuss possible ways to extend
      this model incorporating new experimental results and to generalize it along the
      new emerging trends in network theories of immune response. Our work also
      illustrates some of the relative advantages and disadvantages of the discrete and
      continuum formulations of the models of immune response.

PMID- 8289460
TI  - Minimum evolution and goodness-of-fit.
AB  - Two criteria are much used to evaluate phylogenetic trees constructed from
      distance data: goodness-of-fit and tree length. The exhaustive study of trees
      connecting four taxa shows that in some instances there is a discrepancy between
      these two criteria. The largest tree may be the one that best fits the distances
      at the cost of a negative interior branch length, whereas the shortest tree
      always has the largest interior branch length and is the most supported by
      nucleotid configurations.

PMID- 8289461
TI  - Routes to polymorphism.
AB  - It is well known that for a single, autosomal locus with differential viabilities
      convergence to a stable equilibrium is assured. However if new alleles are
      introduced sequentially by mutation the final equilibrium may depend on the
      particular sequence. Thus the equilibrium to which the population moves will be
      randomly determined. When there is an internal, stable polymorphism there is no
      such randomness in the final equilibrium as there is only the one stable point.
      However the time taken to reach that equilibrium will vary with the order of
      occurrence of mutations, and with the specific set of viabilities. The object
      here is to discuss the possible routes by which an internal polymorphism can be
      reached, and to begin the elucidation of which sets of alleles can be stable in
      their own space.

PMID- 8289462
TI  - Down's syndrome, interferon sensitivity and the development of leukaemia.
AB  - I suggest that the occurrence of transient leukemoid reactions, myelofibrosis and
      leukaemia in Down's syndrome may all result from the greatly increased
      sensitivity of Down's syndrome cells to interferon with consequent aberrant
      antigen expression leading to autoimmune disease. In the bone marrow this may
      manifest itself as premature egress of blast cells (TLR), inflammation and
      imperfect repair (myelofibrosis), and the binding of autoantibodies to cell
      nuclei resulting in malignant transformation leading to leukaemia. Therapy
      consistent with this hypothesis would be directed at blocking the effects of
      gamma interferon, and such therapy might also be useful in certain forms of
      leukaemia associated with viral infection.

PMID- 8289463
TI  - Growth regulation of a T-cell lymphoma via the T-cell receptor.
AB  - Autocrine stimulation is described for a Radiation leukaemia virus (RadLV)
      induced T-cell lymphoma, C6VL/1. The proliferation of this tumour cell line can
      be regulated by several agents, including interleukin-2 (IL-2), antibodies to the
      IL-2 receptor and the T-cell antigen-specific receptor (TCR), as well as RadLV
      retrovirus particles produced by the cell itself. This information has been
      gained using various procedures to slow or arrest C6VL/1 proliferation, including
      the addition of gamma interferon (gamma-IFN) and cell culture at low density. All
      data suggest that these cells can receive growth stimulation via the T-cell
      receptor (TCR) and IL-2 receptor, implicating autocrine stimulation of growth
      involving IL-2 and retroviral gene products.

PMID- 8289464
TI  - Flow cytometric analysis of cell-surface antigen expressions on acute myeloid
      leukemia cell populations according to their cell-size.
AB  - Acute myeloid leukemia (AML) cells which expanded from a single leukemic cell
      show certain degrees of morphological and biological heterogeneity. In the
      present study, we determined cell-surface antigen expressions (CD13, 33, 34 and
      38, and HLA-DR) on AML cells based on their cell-size (large vs small cells) by
      flow cytometry. We found that the cell-surface antigens were more strongly
      expressed on the large leukemic cells than the small cells, regardless of FAB
      subtypes. Furthermore, our preliminary study demonstrated that AML patients who
      showed a relatively small difference in antigen expression between large and
      small leukemic cells had longer remission durations and survival periods,
      compared with those with a more prominent difference in antigen expression. Thus,
      the heterogeneity of AML cells determined by the combination of cell-surface
      antigen expressions and cell-size may be associated with clinically important
      biological behaviors.

PMID- 8289465
TI  - Measurement of the growth parameters of precursor B-acute lymphoblastic leukaemic
      cells in co-culture with bone marrow stromal cells; detection of two cd10
      positive populations with different proliferative capacities and survival.
AB  - A new assay system using the fluorescent probe PKH 26 GL was employed to
      investigate the regulation of precursor B-cell acute lymphoblastic leukaemic
      (ALL) cell growth. PKH 26 GL is a lipophilic fluorescent probe which becomes
      incorporated into the plasma membrane upon the staining of cells. As the amount
      of probe per cell reduces at each cell division, the fluorescence can be used to
      measure cell proliferation. Bone marrow derived ALL cells from seven newly
      diagnosed cases were stained with PKH 26 GL, and cultured for 14 days in control
      cultures without stimulus, or in cultures with preformed human bone marrow
      stromal cell layers. Viable leukaemic cells from these cultures were identified
      on the basis of forward light scatter, 90 degrees light scatter, propidium iodide
      exclusion, PKH 26 GL staining and CD10 expression by flow cytometry at the
      beginning of the culture period and on days 2, 6, 10 and 14. The growth
      parameters of these leukaemic cells were determined by analysis of their pattern
      of PKH 26 GL fluorescence. A higher rate of proliferation and survival of cells
      was observed in cultures with stromal cells compared with control cultures,
      without stromal cells. In the presence of stromal cells, survival and
      proliferation continued throughout the culture period; in contrast in five of
      seven control cultures no viable cells could be detected after 6-10 days.
      Interestingly, two populations of leukaemic cells were distinguished on the basis
      of their different rates of proliferation, when co-cultured with stromal cells.
      The results indicate that this technique provides a means for studying and
      quantitating leukaemic cell growth within a complex stroma-dependent system.

PMID- 8289466
TI  - Significance of pH on differentiation of human erythroid cell lines.
AB  - As physiological factors and compounds, BSA and/or higher pH of the culture
      medium could induce the erythroid differentiation of cells. Optimum pH values of
      the culture medium for higher spontaneous differentiation of KU-812 and K562
      cells after 7 days cultivation were 7.5 and 7.6, respectively. The synergistic
      effects on the differentiation were observed by exposure to hemin under the
      higher pH condition. In the presence of BSA, 25% of KU-812 and 40% of K562 cells
      became benzidine positive. Synergistic effects of BSA and the higher pH of the
      medium were also observed.

PMID- 8289467
TI  - Interleukin-4 (IL-4) inhibits proliferation and spontaneous cytokine release by
      chronic lymphocytic leukaemia cells.
AB  - Previous studies have shown that interleukin-4 (IL-4) may have both stimulatory
      and inhibitory effects on the growth of normal and malignant B-cells in vitro. We
      studied the effects of IL-4 on tumour necrosis factor (TNF) induced and
      spontaneous proliferation (3H-TdR incorporation) and spontaneous release of TNF
      and interleukin-6 (IL-6) by purified B-cell chronic lymphocytic leukaemia (CLL)
      cells in vitro. TNF (100 U/ml) increased 3H-TdR uptake in cells to 700 +/- 302%
      of control (mean +/- S.E., n = 9, p = 0.033). Recombinant IL-4 (10 ng/ml)
      consistently inhibited DNA synthesis in all CLL patients studied. When added at
      the start of 5 day cultures, IL-4 inhibited both spontaneous (41 +/- 17%
      inhibition, n = 3) and TNF induced (46 +/- 5% inhibition, n = 9, p = 0.01) 3H-TdR
      uptake. Similar results were obtained when IL-4 was added after 48 h of culture.
      This effect of IL-4 was dose dependent. Inhibition was not related to clinical
      stage. IL-4 (whether added at T0 or T48h) also inhibited spontaneous release of
      TNF and IL-6 measured at 48 and 120 h. TNF and IL-4 had no consistent effect on
      normal cord blood CD5+ B-cells. These data show that IL-4 has inhibitory effects
      on B-CLL DNA synthesis and also inhibits spontaneous release of IL-6 and TNF in
      vitro. IL-4 may have a role in vivo in reducing proliferation in these B-cell
      malignancies by inhibiting potential autocrine growth loops.

PMID- 8289468
TI  - Pseudorelapse in acute myelomonocytic leukemia after high dose
      methylprednisolone.
AB  - High dose methylprednisolone (HDMP) has been used in induction treatment and in
      leukopenia of acute leukemia. We report the case of a 14-year-old girl with acute
      myelomonocytic leukemia (AMML) who developed a pseudorelapse after receiving an
      oral HDMP trial (30 mg/kg/day PO in the morning for 15 days) to overcome
      neutropenia. She presented with severe bone pain at the end of treatment. Bone
      marrow examination revealed 53% young promyelocytes (some with a large
      nucleolus), 2% myeloblast, 5% monocyte, and increased cellularity. Bone pain and
      promyelocytes regressed spontaneously while maintenance treatment continues. We
      advise that a pseudorelapse must be borne in mind after HDMP and probably GM-CSF
      treatments in acute leukaemias.

PMID- 8289469
TI  - Total loss of p53 DNA sequences in acute myeloid leukemia.
AB  - Mutations of the p53 tumour suppressor gene on chromosome 17p are a common
      genetic change in the malignant progression of many cancers. Here we report a
      case of a 71-year-old man with haematological, cytofluorimetric and cytochemical
      findings consistent with a 'de novo' M2 acute myeloid leukaemia (AML). A complex
      karyotype including a whole chromosome 17 and a t(17;?) (p11;?) was present in 8
      of 10 metaphases of bone marrow cells. Southern blot analysis of the bone marrow
      DNA showed a specific loss of p53 gene in the AML cells. As far as we know, this
      is the first report of a deletion of both p53 alleles in leukaemia. The effect of
      the loss of p53 on the course of AML is discussed.

PMID- 8289470
TI  - Marrow macrophages--pharmacologic sanctuary for pluripotent stem cells?

PMID- 8289471
TI  - The Met/hepatocyte growth factor receptor (HGFR) gene is overexpressed in some
      cases of human leukemia and lymphoma.
AB  - The proto-oncogene c-met encodes a heterodimeric (alpha, beta) tyrosine kinase
      receptor which binds the hepatocyte growth factor (HGF). Recently, overexpression
      of the Met/HGF receptor gene has been detected in fresh samples of carcinomas and
      in epithelial tumor cell lines but not in cell lines derived from human leukemia
      and lymphoma. Our analysis of 50 primary samples of human leukemia and lymphoma
      and 23 hematopoietic cell lines revealed expression of mRNA and protein of the
      met/HGF receptor in 6 out of the 73 hematopoietic tumor samples analyzed. Four of
      the six samples positive for expression of the Met/HGF receptor gene were derived
      from patients with Hodgkin's disease. In addition, in one Burkitt's lymphoma cell
      line and in one acute myeloid leukemia (AML), expression of the Met/HGF receptor
      gene was detected. In normal unstimulated lymphocytes, granulocytes or monocytes
      we did not find expression of the Met/HGF receptor gene. Upon stimulation with
      the phorbol ester TPA we detected a weak expression of Met/HGF receptor specific
      transcripts of 9.0 kb in peripheral blood mononuclear cells of a healthy donor.
      Cytogenetic analyses of three of the four cell lines which express the Met/HGF
      receptor gene revealed structural or numerical abnormalities of the long arm of
      chromosome 7, where the Met/HGFR gene is located, in each of the three cell lines
      analyzed. In one of these cell lines (L540) the Met/HGFR gene is translocated to
      a marker chromosome. Southern blot and pulsed field gel electrophoresis
      experiments did not show any rearrangement in a region of 600 kb around the
      Met/HGF receptor gene excluding an activation of Met/HGFR by a TPR/Met oncogenic
      rearrangement as described for MNNG-HOS cells and for some gastric tumors. Our
      data indicate that the Met/HGFR gene is deregulated in a few cases of human
      leukemia, Burkitt's lymphoma and Hodgkin's disease possibly by chromosomal
      rearrangements resulting in an overexpression of the normal Met/HGF receptor mRNA
      and protein without formation of a hybrid gene.

PMID- 8289472
TI  - Rapid achievement of PML-RAR alpha polymerase chain reaction (PCR)-negativity by
      combined treatment with all-trans-retinoic acid and chemotherapy in acute
      promyelocytic leukemia: a pilot study.
AB  - The reverse transcriptase-polymerase chain reaction (RT-PCR) for the fusion
      transcript of PML-RAR alpha can be used to detect minimal residual disease (MRD)
      in acute promyelocytic leukemia (APL). We have applied a semi-quantitative two
      step PCR assay (sensitivity: step 1 = 1 in 10(3) cells; step 2 = 1 in 10(6)
      cells) to monitor the dynamics of MRD after combined therapy with all-trans
      retinoic acid (ATRA) and chemotherapy (CT) in 5 patients in whom complete
      clinical remission (CR) was achieved. The patients received an induction
      treatment with ATRA for 47, 40, 38, 14 or 10 days. In three patients ATRA was
      followed by CT. Two patients with hyperleukocytosis at diagnosis or after ATRA
      received an overlapping CT starting from day 3 or 7. Four of the five patients
      became two-step PCR-negative in their bone marrow within 43 to 82 days after
      onset of therapy. Two-step PCR-negatively was achieved with ATRA plus one course
      of CT in these four patients who are still in continuous complete remission after
      19, 18, 7 and 5 months. One of these patients did not even receive consolidation
      CT because of congestive heart failure. The fifth patient remained second-step
      PCR-positive and relapsed after 5 months. Our results indicate that the combined
      regimen can rapidly reduce MRD below a detection limit of 1 in 10(6) cells within
      1-3 months and that these results can even by achieved by a short course of ATRA
      together with only one cycle of CT.

PMID- 8289473
TI  - Ras point mutations occur in acute myeloid leukemia with illegitimate T-cell
      receptor delta gene rearrangement.
AB  - Mutations in the ras proto-oncogenes are the most frequently observed molecular
      alteration in acute myeloid leukemia (AML). Whether ras mutations occur as late
      or relatively early events in the multistep process of myeloid transformation,
      remains an open question. We previously described illegitimate T-cell receptor
      (TCR)-delta gene rearrangements in a subset of AML. These recombinations were
      detected in 9 out of 100 de novo AML cases. Southern blot analysis suggested the
      presence of these recombinations in the vast majority of AML cells and thus could
      be used as clonal markers. In order to more accurately define the role of ras
      proto-oncogene mutations in the multistep process of malignant transformation in
      myeloid leukemias, we performed single strand conformation polymorphism (SSCP)
      assays, slot blot and direct sequencing analysis on these nine cases with
      illegitimate TCR delta gene rearrangements. Ras proto-oncogene mutations were
      found in three of nine cases. Interestingly, SSCP, slot blot and sequencing
      suggested the presence of the respective mutations in most of the leukemic cells.
      Thus, ras mutations presumably occurred early in the process of transformation in
      these three cases.

PMID- 8289474
TI  - The SCL protein displays cell-specific heterogeneity in size.
AB  - SCL protein production was examined in a variety of hemopoietic cell lines by
      immunoblotting using specific polyclonal antisera. SCL protein was detected in
      erythroid, megakaryocyte, mast and early myeloid cell lines, as well as in
      several lymphoid leukemia cell lines which are known to harbor SCL gene
      rearrangements. In most cell lines, proteins of molecular weight 49 and 44 kDa
      were found, however two myeloid cell lines expressed only lower molecular weight
      species of 24 and 22 kDa. This size discrepancy appeared to be due to cell
      specific translational regulation, since overexpression of a retrovirally
      transfected SCL gene yielded the higher molecular weight forms in most cell lines
      (GP+E-86, AT2.5, M1) but only the 22 kDa form in the myeloid cell line, WEHI
      3B/D+. Overexpression of full-length SCL protein in the lymphoid cell lines,
      SupT1 and Raji, did not alter cell phenotype and there was no evidence for
      autoregulation of SCL transcription. The restricted pattern of SCL protein
      synthesis is consistent with the restricted expression of SCL mRNA documented
      previously. In addition, the present results indicate that SCL protein size was
      determined by regulation of translation in a cell-specific manner.

PMID- 8289475
TI  - Oral induction and consolidation of acute myeloid leukemia with etoposide, 6
      thioguanine, and idarubicin (ETI) in elderly patients: a randomized comparison
      with 5-day TAD. Finnish Leukemia Group.
AB  - In order to study the efficacy of an oral induction and consolidation regimen in
      the treatment of acute myeloid leukemia (AML) in elderly patients assessed not to
      tolerate full-scale intensive chemotherapy, 51 patients over 65 years of age with
      newly diagnosed AML were randomized to receive two cycles of either totally oral
      ETI (25 patients) or conventional 5-day TAD (26 patients). The median age of the
      patients was 73 years, range 65-87 years. Thirty-eight patients had de novo AML
      and the remaining patients AML subsequent to myelodysplastic syndrome ((n = 11)
      or treatment related AML (n = 2)). ETI consisted of etoposide 80 mg/m2 and
      thioguanine 100 mg/m2 twice a day on days 1-5, and idarubicin 15 mg/m2 on days 1
      3, all given orally. TAD consisted of oral thioguanine and i.v. cytarabine, both
      in the dose of 100 mg/m2 twice a day on days 1-5, and daunorubicin 60 mg/m2 on
      day 5. The maintenance treatment was daily oral mercaptopurine 70 mg/m2 and
      weekly oral methotrexate 12 mg/m2. In the ETI group complete remission (CR) was
      achieved in six patients after the first cycle and in nine more patients after
      the second cycle. The CR rate was 15/25 = 60%. The corresponding figures for the
      TAD group were four and two remissions, CR rate 6/26 = 23% (p = 0.007). The
      survival was significantly longer in the ETI arm (p = 0.042). The median survival
      was 9.9 months in the ETI group and 3.7 months in the TAD group. There were no
      significant differences in the side effects between the two arms. In conclusion,
      the totally oral ETI regimen resulted in a significantly higher remission rate
      and longer survival than the 5-day TAD regimen in elderly patients with AML, with
      no more toxicity.

PMID- 8289476
TI  - Potential molecules implicated in downstream signaling pathways of p185BCR-ABL in
      Ph+ ALL involve GTPase-activating protein, phospholipase C-gamma 1, and
      phosphatidylinositol 3'-kinase.
AB  - Constitutive activation of BCR-ABL tyrosine kinase fusion protein has been shown
      to be an essential step in the pathogenesis of Philadelphia chromosome (Ph)
      positive leukemias. We studied the tyrosine phosphorylated proteins which might
      be involved in the signaling pathway p185BCR-ABL using a Ph-positive acute
      lymphoblastic leukemia cell line. p185BCR-ABL but not p145c-abl was
      constitutively phosphorylated on tyrosine in this cell line. p21ras GTPase
      activating protein (GAP) was physically associated with p185BCR-ABL, but not with
      p145c-abl, and GAP-associated proteins p62/p190 were found to be tyrosine
      phosphorylated. Furthermore, p185BCR-ABL was also physically associated with
      phospholipase C-gamma 1 (PLC-gamma) and phosphatidylinositol 3'-kinase (P13
      kinase). Concomitantly, both PLC-gamma and p85 subunit of P13-kinase are tyrosine
      phosphorylated in the cells with p185BCR-ABL. These data suggest that GAP, GAP
      associated proteins, PLC-gamma, and P13-kinase may participate in downstream
      signaling for p185BCR-ABL tyrosine kinase.

PMID- 8289477
TI  - Effects of DNA topoisomerase II inhibitors on human bone marrow progenitor cells.
AB  - Topoisomerase II (topo II) is a target for many cytotoxic agents. Two
      observations, however, warrant caution in their therapeutic use: first, these
      agents can inhibit differentiation and second, perturbations in function render
      the enzyme error-prone. Illegitimate recombination events occurring at sites
      where topo II acts in differentiation could be particularly important in the
      development of secondary malignancies (relatively frequent after therapy with
      agents that target topo II). Topo II inhibitors are heterogeneous in mechanisms
      of action; in site-specificity of cleavable complex 'entrapment' (where present)
      and in the relative potency against the two topo II isoforms, all potentially
      influencing the site of maximum DNA damage. The object of this study was to
      examine the effect of topo II inhibitors on human haemopoietic precursor cells,
      to determine which have most impact on differentiation. We selected two which act
      via cleavable complex entrapment, but with different site preferences (m-AMSA and
      VP-16), and two acting via other mechanisms (merbarone and fostriecin). VP-16 and
      m-AMSA showed similar patterns with low dose stimulation of granulocyte
      macrophage colony formation and high dose inhibition of all colony types. The
      stimulation was accompanied by an increase in colony size and blast content,
      consistent with a low dose inhibition of differentiation. Forstriecin, in
      contrast, stimulated predominantly mixed and erythroid colonies. Merbarone failed
      to increase colony formation. Neither produced substantial inhibition of colony
      formation. The effects on granulocyte-macrophage progenitors were confirmed using
      7-day suspension cultures, using nitroblue tetrazolium (NBT) reduction and 3
      4,5,dimethylthiazol 2,5-diphenyl tetrazolium bromide (MTT) assays for
      differentiated cells and total cell mass, respectively. These results demonstrate
      that the effects of topo II inhibitors on haemopoietic cell proliferation and
      differentiation are agent-specific and can involve lineage-restricted partial
      inhibition of differentiation.

PMID- 8289479
TI  - Estimation of effective and total erythropoiesis in myelodysplasia using serum
      transferrin receptor and erythropoietin concentrations, with automated
      reticulocyte parameters.
AB  - The erythroid abnormality in patients with myelodysplasia (MDS) is
      multifactorial, with ineffective erythropoiesis and poor in vitro progenitor
      response to erythropoietin (EPO). Serum EPO concentration is variable among
      patients for a given haemoglobin concentration. We studied 19 non-transfusion
      dependent patients with MDS, and 13 healthy elderly control subjects in an
      attempt to define the factors governing variability in serum EPO and to further
      characterise the anaemia of MDS. Serum EPO concentration was appropriate for the
      degree of anaemia in 15/19 MDS patients, and was positively related to mean cell
      volume (MCV), mean cell haemoglobin (MCH), and percentage highly fluorescent
      reticulocytes (% HFR), but not to absolute or percentage reticulocyte count.
      Although the observed/predicted ratio for serum transferrin receptor (TfR)
      concentration was low in 12 of 19 MDS subjects, no relationship to haemoglobin
      concentration, reticulocytes or serum EPO was seen. Serum TfR was positively
      correlated with WBC and platelet counts. Serum TfR was higher in patients with
      sideroblastic anaemia than refractory anaemia. Standardized in vivo p50 was
      positively correlated to red cell 2,3 diphosphoglycerate concentration, although
      this was not the only factor influencing the oxygen dissociation curve. We
      conclude that effective erythroid output responsive to endogenous EPO drive in
      MDS is positively related to MCV, MCH and % HFR. Serum TfR may not represent
      effective output as precisely as % HFR, but may be proportional to total marrow
      erythropoietic activity.

PMID- 8289478
TI  - Antisense BCR-ABL oligonucleotides induce apoptosis in the Philadelphia
      chromosome-positive cell line BV173.
AB  - BCR-ABL antisense oligonucleotides can specifically reduce colony formation of
      early hematopoietic progenitor cells from chronic myeloid leukemia (CML)
      patients. Little is known about the mechanism of this inhibition. We studied the
      inhibition of the bcr-abl oncogene using fluorescein-labeled phosphorothioate
      oligonucleotides in the Philadelphia chromosome-positive cell line BV173.
      Oligonucleotide stability, uptake, bcr-abl mRNA degradation, inhibition of cell
      proliferation, and cell death were studied. The oligonucleotide uptake was
      directly dependent on the extracellular concentration and was constant over the
      first 18 h of incubation. After that the uptake rate decreased. We detected a
      decrease in bcr-abl mRNA after 3 days of treatment with antisense
      oligonucleotides, but much less in controls. The controls used in the experiments
      were the sense oligonucleotide, equimolar amounts of sense and antisense, and an
      untreated control. Antisense oligonucleotides completely inhibited cell growth of
      BV173 cells and did not inhibit growth of HL-60 cells, whereas control
      oligonucleotides had no such effect on either cell line. An oligonucleotide
      specific for the other CML breakpoint was also effective in reducing cell growth
      of BV173. By the use of a DNA double staining technique to discriminate between
      necrotic and apoptotic cells, we detected a large number of apoptotic cells in
      antisense treated BV173 cultures after 5 days of treatment as compared to
      controls. We conclude that antisense BCR-ABL oligonucleotides reduce bcr-abl mRNA
      expression in BV173 cells mainly in a sequence-specific manner and induce
      apoptosis.

PMID- 8289480
TI  - Cancer procoagulant in the human promyelocytic cell line NB4 and its modulation
      by all-trans-retinoic acid.
AB  - Acute promyelocytic leukemia (APL) cells express different types of procoagulant
      activity (PCA), including tissue factor (TF), and cancer procoagulant (CP). The
      aim of this study was to investigate whether the NB4 cell line, the first ever
      isolated human APL line, with the typical t(15;17) chromosomal balance
      translocation, possess CP as well as the cells freshly isolated from APL
      patients. Secondly, since the NB4 line is maturation inducible by all-trans
      retinoic acid (ATRA), we wanted to verify whether CP, if present, was affected by
      ATRA treatment. The NB4 cells were able to shorten the recalcification assay of
      normal human plasma (total PCA). To distinguish CP in the assay for clotting
      activity, two criteria were used, the independence from factor VII to trigger
      blood coagulation and the sensitivity to cysteine proteinase inhibitors. Forty
      seven per cent of total PCA of cell extracts was found to be FVII-independent
      PCA. A similar proportion of FVII-independent activity (42%) was detected in the
      cell serum-free supernatants. The activity was significantly decreased by
      cysteine proteinase inhibitors, including HgCl2, lodoacetic acid and Z-Ala
      AlaCHN2. Additionally CP was directly identified and quantified by an
      immunocapture enzyme assay. The mean +/- SD concentration of CP detected by this
      assay in the NB4 cells, before any treatment, was 1.89 +/- 0.5 microgram/mg
      protein. Treatment of NB4 cells with 10(-6) M ATRA for 5 days significantly
      decreased the expression of CP, which became virtually undetectable by the
      clotting assay, and was 64% less than the untreated control by the immunocapture
      enzyme assay. This study provides the first evidence that the human promyelocytic
      cell line NB4 possess CP. The expression of this procoagulant is modulated by
      ATRA.

PMID- 8289481
TI  - A randomized phase II study of low-dose cytosine arabinoside (LD-AraC) plus
      granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in myelodysplastic
      syndromes (MDS) with a high risk of developing leukemia. EORTC Leukemia
      Cooperative Group.
AB  - In a randomized phase II study, patients with myelodysplastic syndromes (MDS)
      with 10-30% blasts in the bone marrow and hematopoietic failure were treated with
      low-dose Ara C (2 x 10 mg/m2 subcutaneously (s.c.) days 1-14) and rhGM-CSF (fully
      glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day s.c.) given
      either following Ara C (days 15-21) or simultaneously (days 8-14) for 1-5 cycles.
      108 patients with a median age of 65 years, range 17-80 years and refractory
      anemia with an excess of blasts (RAEB, n = 54), RAEB with transformation (RAEBt,
      n = 50) or with chronic myelomonocytic leukemia (CMML, n = 4) were evaluable.
      Complete remission was achieved in 15 cases (14%), 11 had a partial response
      (10%), and 16 a minor response (15%). Stable disease was reached in 35 cases
      (32%). There were 16 cases of toxic death (15%), progression occurred in 15
      patients (14%). No differences existed between the two treatment arms with
      respect to response and duration of response. Prognostic factors for poor
      response included the presence of cytogenetic abnormalities and a history of
      previous blood transfusions. Major adverse events during treatment were
      hemorrhage (55%), infections (54%), and fever associated with GM-CSF
      administration (40%). The overall response rate ws 39%, median duration was 12.5
      months from start of treatment which allowed responding patients to lead good
      quality life without further therapy. The question whether the combination is
      indeed superior to LD-Ara C alone is not settled but will be evaluated in an
      ongoing clinical trial.

PMID- 8289482
TI  - Comparative effects of quinine and cinchonine in reversing multidrug resistance
      on human leukemic cell line K562/ADM.
AB  - We have previously suggested that quinine and cinchonine could be good candidates
      for clinical circumvention of multidrug resistance (MDR) in hematological
      malignancies because of their tolerance and their retained efficacy in serum. In
      the present study, we have used the well-characterized multidrug resistant human
      leukemic cell line K562/ADM to compare the effect in vitro of quinine and
      cinchonine on doxorubicin, mitoxantrone, and vincristine uptake and cytotoxicity.
      In serum-free medium, quinine induced a dose-dependent increase of doxorubicin
      uptake reaching about 200% at 40 microM, while it had a slight and no effect on
      mitoxantrone and vincristine uptake respectively. In the same conditions,
      cinchonine induced a rapid and significant increase in the accumulation of the
      three drugs, reaching a plateau phase between 5 and 10 microM. Quinine and
      cinchonine induced both potentiation of doxorubicin, vincristine and mitoxantrone
      cytotoxicity in K562/ADM cells. However, quinine reached a plateau phase at 10
      microM, while cinchonine had a maximal effect at 5 microM and was significantly
      more potent at low concentrations. When diluted in plasma, cinchonine was less
      bound to proteins than quinine. The free fraction of alkaloids was 37-55% for
      cinchonine and 20-30% for quinine. Cinchonine-induced enhancement of vincristine
      cellular accumulation was little modified by plasma proteins. When incubated in
      whole blood, the fraction of cinchonine trapped in red blood cells was rapidly
      and completely exchangeable with plasma. We conclude that cinchonine is a
      stronger inhibitor of MDR than quinine.

PMID- 8289483
TI  - Binding of BCR/ABL junctional peptides to major histocompatibility complex (MHC)
      class I molecules: studies in antigen-processing defective cell lines.
AB  - Leukaemia-specific proteins may be recognized by T-lymphocytes as neoantigens if
      peptides corresponding to mutated sequences bind to major histocompatibility
      complex (MHC) molecules on leukaemic cells. We studied the ability of a series of
      synthetic peptides corresponding to the junctional sequences of BCR/ABL proteins
      to bind to class I molecules in two human cell lines, LBL 721.174 (T2) (HLA-A2,
      B5) and BM36.1 (HLA-A1, B35), and one murine cell line RMA-S (H-2Kb, Db). These
      cell lines are defective in intracellular peptide loading of class I molecules,
      resulting in markedly reduced cell surface class I expression: class I expression
      can be rescued by provision of peptides binding to the alleles expressed by the
      mutant cell. Eighteen peptides spanning the junctional sequences of the b2a2 and
      b3a2 proteins were tested for their ability to rescue expression of the class I
      alleles borne by these cells using flow cytometry. Allele-specific control
      peptides known to bind HLA-A2, HLA-B35, H-2Kb and H-2Db increased expression of
      these alleles 2- to 3-fold: 0/18 BCR/ABL peptides enhanced HLA-A2, HLA-B35 or H
      2Kb expression, but three b2a2 peptides consistently increased H-2Db expression.
      These results suggest that BCR/ABL junctional peptides are unlikely to be
      presented to T-cells in association with HLA-A2, HLA-B35 or H-2Kb. Conversely,
      the finding that some b2a2 peptides bind specifically to H-2Db suggests that a
      murine model of graft-versus-leukaemia (GVL) could be constructed.

PMID- 8289484
TI  - Establishment of a new cell line with the characteristics of a multipotential
      progenitor from a patient with chronic myelogenous leukemia in early
      erythroblastic crisis.
AB  - A novel cell line (KH88) was established from a patient with chronic myelogenous
      leukemia in blastic crisis. The leukemic blasts had the features of
      undifferentiated blasts with basophilic agranular cytoplasm and they were focally
      positive for acid phosphatase and alpha-naphthyl acetate esterase. CD36, CD33,
      HLADR, and CD71 were expressed on the surfaces of the blast cells. Most blasts
      were positive for platelet peroxidase activity, and some of them had granules
      containing aggregates of ferritin molecules. These findings were compatible with
      those of 'early' erythroblastic leukemia, this established cell line (KH88)
      having similar characteristics, and actually producing hemoglobin A and
      hemoglobin F. Although the KH88 cells were negative for megakaryocytic markers,
      they were induced to express CD41 by phorbol ester. Further, a few KH88 cells
      were positive for myeloperoxidase. This cell line was thus revealed to have the
      capacity to differentiate into three lineages, providing a useful model for
      studying the differentiation of multipotential stem cells. Moreover, a subline of
      KH88 had a peculiar chromosome abnormality, del(3)(q21q25); it would be useful to
      study the significance of this chromosomal abnormality.

PMID- 8289485
TI  - Assessment of proliferative responses to granulocyte-macrophage colony
      stimulating factor (GM-CSF) in acute myeloid leukaemia using a fluorescent ligand
      for the nucleoside transporter.
AB  - Nucleoside transporter expression has been linked to proliferation in a variety
      of haemopoietic cell types. Granulocyte-macrophage colony-stimulating factor (GM
      CSF) was given for 72 h before commencing chemotherapy in 15 patients with
      relapsed or refractory acute myeloid leukaemia (AML) and in 11 patients serial
      bone marrows were taken for measurement of [3H]thymidine labelling index, Ki-67
      positivity and maximal binding of 5-(SAENTA-x8)-fluorescein, a flow cytometry
      ligand which enumerates nucleoside transporter sites. GM-CSF caused proliferation
      of marrow myeloblasts in eight of 11 patients, while in three patients there was
      no change in proliferative indices. The expression of nucleoside transporters
      increased up to 4-fold in the myeloblasts from the patients showing a
      proliferative response to GM-CSF but there was no increase in transporters on the
      myeloblasts from the three non-responding patients. A close correlation was found
      between the fold increase in nucleoside transporter expression and the fold
      increase in labelling index of marrow myeloblasts (r = 0.86, n = 9, p < 0.01). In
      one patient with acute megakaryoblastic leukemia, GM-CSF caused parallel
      increases in labelling index, Ki-67 positivity and numbers of nucleoside
      transporters on peripheral blood blast cells. Thus induction of proliferation by
      cytokine increases the expression of nucleoside transporters on leukaemic
      myeloblasts studied in serial samples from the same source (bone marrow or
      blood). The suitability of 5-(SAENTA-x8)-fluorescein for two colour flow
      cytometric analysis allows the rapid enumeration of nucleoside transporters in
      the myeloblast compartment of heterogeneous marrow samples.

PMID- 8289486
TI  - An optimized multiplex polymerase chain reaction (PCR) for detection of BCR-ABL
      fusion mRNAs in haematological disorders.
AB  - A rapid and simple polymerase chain reaction (PCR) method is described that is
      capable of identifying any of the BCR-ABL transcripts that have yet been
      described in chronic myeloid or acute lymphoblastic leukaemia. Randomly primed
      cDNA is synthesized from leucocyte RNA and amplified in a single reaction
      containing four oligonucleotide primers (multiplex PCR). Different size products
      are generated from ela2 (p190) and b3a2 or b2a2 (p210) BCR-ABL transcripts which
      are readily and unambiguously distinguishable after agarose gel electrophoresis
      without the need for either nested PCR or hybridization. Chronic myeloid
      leukaemia cells are readily detectable even when diluted 1 in 1000 with normal
      blood. Samples which do not have BCR-ABL rearrangements produce a single band
      derived from the normal BCR gene, and the presence of this band controls for
      adequate RNA and cDNA preparation. Using this assay we have detected BCR-ABL
      transcripts in a variety of haematological disorders.

PMID- 8289487
TI  - Investigation of methylation at Hha I sites using the hypervariable probe M27
      beta allows improved clonal analysis in myeloid leukaemia and demonstrates
      differences in methylation between leukaemic and remission samples.
AB  - The methylation-sensitive enzyme Hha I has been used to assess the differentially
      methylated patterns on active and inactive X-chromosomes at the DXS255 locus
      recognized by the hypervariable probe M27 beta. The X-chromosome inactivation
      ratios obtained from 37 haematologically normal females using PstI and HhaI and
      correlated well with results obtained using PstI Hpa II (r = 0.97), and in 19
      individuals with values obtained probing for either phosphoglycerate kinase or
      hypoxanthine phosphoribosyl transferase (r = 0.92). At least one Hha I site was
      found to be unmethylated on all alleles on inactive X-chromosomes. A monoclonal
      or oligoclonal pattern could be obtained by digestion with Hha I in 18/22 (82%)
      patients with acute myeloid leukaemia who had previously shown hypermethylation
      of both alleles using Hpa II, although in six of these patients differences in
      methylation could still be demonstrated between leukaemic and remission samples.

PMID- 8289488
TI  - A case of Philadelphia-negative, M-BCR rearranged eosinophilic leukaemia with
      trisomy 8 localized by in situ hybridization.
AB  - A case of Ph-negative M-BCR rearranged eosinophilic leukaemia with clonal
      cytogenetic abnormalities is presented. In addition to involvement of the short
      arm of chromosome 12 (12p12?13), the malignant nature of the eosinophils was
      confirmed by the demonstration of trisomy 8 by in situ hybridization.

PMID- 8289489
TI  - Primary granulocytic sarcoma of the testis.
AB  - An unusual case of a 44-year-old patient with primary left testicular
      granulocytic sarcoma is presented. Iliac and paraaortic lymph node involvement
      was also demonstrated at staging laparotomy. The patient was treated with left
      orchiectomy and early intensive chemotherapy, but relapsed with a right
      testicular mass 14 months later. No evidence of leukemic progression was found at
      that time, and he was treated with right orchiectomy, combined with irradiation
      to the scrotum, inguinal, iliac and paraaortic lymph nodes. Unfortunately, he
      developed myelogenous leukemia 7 months later. A complete remission of 6 months
      duration was achieved with combination chemotherapy. The patient then relapsed,
      and an effort to induce a second remission was unsuccessful. He eventually died
      almost 3 years after initial diagnosis. We conclude that primary granulocytic
      sarcoma represents a systemic disease. Despite early intensive treatment its
      prognosis remains poor.

PMID- 8289490
TI  - HTLV-1-like particles and HTLV-1-related DNA sequences in an unambiguous case of
      Sezary syndrome.
AB  - An unambiguous case of Sezary syndrome associated with the presence of unusual
      retroviral infection markers is described. The blood smear showed 15% typical
      Sezary cells but also rare atypical lymphocytes with convoluted nuclei, evocative
      of characteristic adult T-cell leukemia (ATL) flower cells. However, the patient
      did not present any clinical or biological manifestations of ATL, and human T
      cell leukemia virus type 1 (HTLV-1) serology was consistently negative. After
      being cultured for 4 months, peripheral blood mononuclear cells (PBMC) produced
      typical type C retrovirus-like particles with budding forms strongly resembling
      HTLV-1 virions. The producer cells did not express HTLV-1-specific antigens
      detectable by indirect immunofluorescence (IIF). Southern blotting of uncultured
      PBMC DNA, submitted to digestion with the restriction enzymes PstI and SacI, and
      hybridized with a full genomic HTLV-1 probe, showed the presence of specific
      homologous sequences, absent in all of the healthy donor control PBMC DNAs. These
      HTLV-1-like sequences presented a restriction enzyme pattern distinct from that
      of the HTLV-1 prototype genome and of other HTLV-1 proviruses studied up to now.
      Polymerase chain reaction (PCR) with highly conserved HTLV-1 derived pol and env
      primers was consistently negative with the patient's DNA. All these results taken
      together suggest that our patient carries a retroviral agent partially homologous
      to, but probably different from HTLV-1. The possibility is discussed that this
      type of retroviral agent might be associated with a subtype of cutaneous T-cell
      lymphoma (CTCL) represented by a typical Sezary syndrome with a very low
      percentage of ATL-like flower cells in the blood smear.

PMID- 8289491
TI  - P190BCR-ABL chronic myeloid leukaemia: the missing link with chronic
      myelomonocytic leukaemia?
AB  - Two-thirds of patients with Philadelphia (Ph) chromosome-positive acute
      lymphoblastic leukaemia (ALL) have a breakpoint in the minor breakpoint cluster
      region (m-bcr) of the BCR gene, which results in an e1a2 transcript and a P190BCR
      ABL fusion protein. This type of genomic rearrangement occurs very rarely in
      chronic myeloid leukaemia (CML); it has been reported in only four cases. We
      describe here a fifth case of P190 CML in which the cytomorphological
      characteristics were intermediate between CML and chronic myelomonocytic
      leukaemia (CMML). This case, and the four reported previously, had a consistent
      and significant monocytosis with a low neutrophil/monocyte ratio in the
      peripheral blood, resembling CMML. On the other hand, they also had a high
      percentage of circulating immature granulocytes, basophilia and low neutrophil
      alkaline phosphatase (NAP) score, which are more commonly found in classical CML.
      Thus, P190 CML may be a specific form of CML, in which the myeloproliferative
      process includes the monocytic, as well as the granulocytic lineage. Since the
      molecular defect in CML is thought to involve a pluripotent stem cell, the
      different effects of P210BCR-ABL and P190BCR-ABL in CML must reflect the somewhat
      wider spectrum of activity of the P190BCR-ABL. Other patients with atypical CML
      or CMML who lack a Ph chromosome may also have an m-bcr breakpoint which would
      not be detected on standard Southern blots, but which would be detectable by
      polymerase chain reaction amplification of reverse transcribed RNA.

PMID- 8289492
TI  - Effect of retinoic acid (RA) on myeloid progenitors in normal bone marrow (BM)

PMID- 8289493
TI  - When to initiate anti Pneumocystis carinii prophylaxis in acute lymphoblastic
      leukemia treatment?

PMID- 8289494
TI  - In vitro cytotoxicity of mitoxantrone, daunorubicin and doxorubicin in untreated
      childhood acute leukemia.
AB  - Mitoxantrone (MIT) has not been studied as a single agent in children with
      untreated leukemia. The antileukemic activity of MIT in these patients and its
      activity in relation to clinical and cell biological features is unknown. We
      studied the in vitro cytotoxicity of MIT, daunorubicin (DNR) and doxorubicin
      (DOX) in untreated childhood acute lymphoblastic leukemia (ALL, n = 131) and
      acute nonlymphoblastic leukemia (ANLL, n = 20) samples, using the MTT assay.
      There were marked interindividual differences in resistance to all three drugs. A
      strong, significant cross-resistance was found in ALL between MIT, DNR and DOX.
      All samples of the T-lineage, a prognostically unfavorable immunophenotype,
      however, were significantly more resistant to DNR and DOX, but not to MIT, than
      common or pre-B ALL samples. ALL cells from children with a prognostically
      unfavorable age at diagnosis, especially those < 2 years, showed a relative
      resistance to all three drugs compared to the intermediate age-group. This was
      found within all patients, but also within the common or pre-B ALL cases only.
      Sex, white blood cell count, or FAB type was not related to in vitro drug
      resistance. None of the three drugs showed an overall preferential activity in
      ALL or ANLL. We conclude that the in vitro antileukemic activity of MIT, DNR and
      DOX is related to certain clinical and cell biological features. There were no
      major differences between the three drugs in antileukemic activity, except that T
      ALL samples were more resistant than common or pre-B ALL samples to DNR and DOX,
      while MIT was equally active in these two immunophenotypes.

PMID- 8289495
TI  - Large cell non-Hodgkin lymphoma of childhood: clinical characteristics and
      outcome.
AB  - Less is known about the clinical features and treatment outcome in pediatric
      large cell non-Hodgkin lymphoma (NHL) than the lymphoblastic and small noncleaved
      cell subtypes of NHL. To characterize presenting features and assess possible
      risk factors associated with this diagnosis, we analyzed data for 91 patients
      treated on a succession of multiagent regimens from 1975 to 1990. Five-year event
      free survival (EFS) (+/- SE) was related to disease extent (St Jude system):
      stage I (n = 24), 95% +/- 5%; stage II (n = 20), 84% +/- 9%; stage III (n = 38),
      50% +/- 10%; and stage IV (n = 9), 22% +/- 11%. Advanced stage disease, age < or
      = 5 years and serum LDH > 500 U/l were associated with poorer EFS in the
      univariate model (p < 0.001, 0.005, and 0.002, respectively). In the multivariate
      model, advanced stage and age retained prognostic significance (p = 0.001 and
      0.02, respectively), but LDH did not. Among limited stage cases, age < or = 5
      years was the only adverse risk feature (p = 0.016); treatment era (pre- vs. post
      1979) was the only significant feature in patients with advanced disease (p =
      0.004). Intrathoracic primaries were associated with a better outcome than other
      sites among the 38 stage III patients (p = 0.005). Only one of eight patients
      with bone marrow disease remains failure-free. The excellent results for limited
      stage pediatric large cell NHL permit consideration of treatment modifications to
      decrease toxicity; for cases with advanced disease, especially those with bone
      marrow involvement, novel therapeutic approaches are clearly needed.

PMID- 8289496
TI  - Early diagnosis of gastric lymphoma: gene rearrangement analysis of endoscopic
      biopsy samples.
AB  - The diagnosis of gastric lymphoma in endoscopic biopsy specimens remains
      difficult despite the emergence of accepted criteria for the histologic diagnosis
      of lymphomas originating from mucosa-associated lymphoid tissue (MALT). The
      sensitivity and validity of immunoglobulin (Ig) gene rearrangement analysis of
      mucosal biopsies for the diagnosis of malignant B-cell lymphoma were investigated
      in comparison with conventional histology and immunohistology. Biopsy specimens
      from 34 different endoscopies of 20 patients with a previous history, or
      tentative diagnosis of gastric lymphoma, and 12 control samples were analyzed for
      the presence of clonal Ig gene rearrangements. A clonal B-cell population was
      detected by Southern blot analysis in all patients with a definitive histologic
      diagnosis of lymphoma. In addition, in two patients the detection of clonal
      rearrangements in biopsy specimens preceded by several months the histologic
      diagnosis of lymphoma, and clonality was confirmed in three further patients
      where histology remained inconclusive. In some cases of low-grade MALT-lymphoma,
      discrete spreading of malignant cells within chronically inflamed mucosa was
      suggested by the presence of identical clonal rearrangements in all
      simultaneously obtained biopsies, with or without histologically detectable
      involvement by lymphoma. Our results show that immunoglobulin gene rearrangement
      studies of endoscopic biopsy samples are an additional powerful tool for the
      diagnosis of gastric lymphoma, especially for detecting early recurrence, and
      improve the preoperative assessment of the extent of mucosal involvement.

PMID- 8289497
TI  - Persistence of self-renewing leukemia cell progenitors during remission in
      children with B-precursor acute lymphoblastic leukemia.
AB  - No effective therapy is available for the majority of the 30-40% of children with
      acute lymphoblastic leukemia (ALL) who relapse. Since the morphologically
      undetectable, or occult, leukemia cells that persist during remission originate
      from the clone present at diagnosis, may also have both the capability to sustain
      the disease and to give rise to relapse, we are evaluating a method of
      identifying them. We have combined, for the first time, an ALL blast colony assay
      (BCA) and the polymerase chain reaction (PCR) to isolate residual leukemia cells
      in remission bone marrow aspirate specimens from eight patients with B-precursor
      ALL during early continuation therapy. We found colony-forming leukemia cells
      with in vitro self-renewal capability that survived chemotherapy for 15 months
      after diagnosis in all sequential specimens from these patients. To verify the
      leukemic nature of these cells their DNA was amplified by PCR and the product
      directly sequenced. In every case, the VHDJH sequence observed at diagnosis was
      found. None of the patients relapsed during this early phase of their treatment,
      consistent with the observation that patients with B-precursor ALL experience
      recurrence late in their course. Since it is possible that some of these
      persistent leukemia cells belong to the leukemia progenitor cell population that
      sustains the disease, the study of them could provide the means to determine the
      mechanisms of relapse.

PMID- 8289498
TI  - Clonal expansion of p53 mutant cells in leukemia progression in vitro.
AB  - Using the polymerase chain reaction followed by single-strand conformation
      polymorphism (PCR-SSCP) analysis and direct nucleotide sequence determination,
      the p53 gene was analyzed in six fresh leukemia samples from which cell lines
      with p53 mutations were established. Mutations of the p53 gene which were
      identical to those in the cell lines were observed in three of the fresh samples.
      In the other three samples, p53 gene mutations were not detected by the
      conventional PCR-SSCP method. However, when analyzed using allele-specific gene
      amplification, less than 10% of the leukemic cell population of the three
      samples, which were below the detection threshold of PCR-SSCP, were shown to have
      p53 gene mutations. Two samples taken at the initial presentation of two
      patients, whose relapse samples were shown to contain p53 mutant clones, were
      also available for analysis. A small population of clonal cells, comprising less
      than 1% of the population, was shown to have p53 gene mutations in both of these
      initial samples. These observations provide a potential biologic basis for the
      frequent findings of p53 mutations in leukemia cell lines and also suggest a
      potential role for p53 mutations in the clonal overgrowth of cells responsible
      for relapse of the disease.

PMID- 8289499
TI  - Efficacy of etoposide and mitoxantrone in patients with acute myelogenous
      leukemia refractory to standard induction therapy and intermediate-dose
      cytarabine with amsidine. Dutch Hematology-Oncology Working Group for Adults
      (HOVON).
AB  - Thirty-seven newly diagnosed patients with acute myeloid leukemia (AML) who were
      not in complete remission (CR) after induction chemotherapy with cytarabine and
      daunorubicin followed by intermediate-dose cytarabine and amsacrine, were treated
      with mitoxantrone and etoposide in a prospective, open multicenter study. The aim
      was to examine the efficacy and the toxicity of mitoxantrone and etoposide in a
      patient population with bad prognosis because of refractoriness to two
      standardized induction courses. Twelve patients attained CR (32.4%). Responders
      were found only among the patients with documented susceptibility (i.e. partial
      remission) to the previous therapy. In responding patients the median remission
      duration and disease-free survival was 15+ months (range 3-52+). Toxicity was
      mainly hematologic and characterized by prolonged hypoplasia; one patient died in
      aplasia. Granulocytes and platelets recovered unexpectedly early in six of 22 non
      responders. This study suggests that AML patients refractory to two standardized
      chemotherapy courses can still attain a durable CR after an additional course,
      here with mitoxantrone and etoposide, provided they show some responsiveness to
      the previously given cytostatic drugs.

PMID- 8289500
TI  - Characterisation of non-concordance in the T-cell receptor gamma chain genes at
      presentation and clinical relapse in acute lymphoblastic leukemia.
AB  - We have analysed the structure of the T-cell receptor gamma chain (TCRG) genes in
      a panel of biopsies taken from 24 patients with acute lymphoblastic leukemia
      (ALL) (13 cALL, one pre-B ALL, two null ALL and eight T-ALL) at presentation and
      at clinical relapse. In the majority of cases (18/24) the structure of these
      genes was concordant, but in a significant minority of cases (6/24) the TCRG
      genes were in a different conformation at different clinical stages. In three of
      these patients (one null ALL, two T-ALL) the clonal TCRG rearrangements detected
      at presentation were absent at relapse possibly as a result of clonal regression.
      In one other patient (cALL), the TCRG locus at relapse was rearranged to V genes
      which are located downstream of the V genes found in the presentation
      rearrangement. This indicates that the relapse leukemic clone is probably the
      result of clonal evolution. In two patients (one cALL, one T-ALL) there were no
      clonally dominant rearrangements of the TCRG genes at presentation, but evidence
      for clonal rearrangements at relapse, possibly as a result of clonal progression.
      The structure of the IgH genes were determined in four of the six patients with
      clonal changes in the TCRG genes and were found to be concordant. The changes in
      TCRG gene structure were not restricted to ALL of any one particular age group,
      phenotype or duration of first remission. These data indicate that the assignment
      of clonal specific markers based upon the sequence of TCRG rearrangements at
      presentation may not always be useful in the detection of minimal residual
      disease in ALL.

PMID- 8289501
TI  - The prognostic significance of deletion of the long arm of chromosome 20 in
      myeloid disorders.
AB  - A review of patients with myeloid disorders presenting to a large cytogenetic
      referral centre over a ten year period was undertaken to assess the clinical
      relevance of the presence of del(20q) in their malignant karyotypes. Twenty-six
      patients were identified, four with myeloproliferative disorders (MPD), 15 with
      myelodysplastic syndromes (MDS) and seven with acute leukemia. The presence of
      del(20q) in four patients with MPD did not appear to adversely affect survival,
      with all patients alive 18 to 184 months post diagnosis. However, the 15 patients
      with MDS had a median survival of only 12 months. Seven of these patients
      developed acute leukemia including three of four patients with refractory anemia
      with ringed sideroblasts (RARS). Of the seven patients with acute leukemia de
      novo and del(20q), six were treated with only two achieving complete remission.
      The median duration of survival for these seven patients was 5 months. These
      results, when compared with published survival data from the MIC Cooperative
      Group, indicated that del(20q) in MDS is associated with a high rate of
      transformation to acute leukemia and a poor prognosis. In de novo acute leukemia,
      del(20q) is associated with a poor response to treatment and reduced survival.

PMID- 8289502
TI  - Cytogenetic findings and results of combined immunophenotyping and karyotyping in
      Hodgkin's disease.
AB  - Cytogenetic studies were performed in 21 cases of Hodgkin's disease. Fourteen
      cases revealed chromosomally aberrant clones which could be fully described in 12
      cases. Two cases showed different unrelated clones and five cases only single
      cell aberrations. Recurrent breakpoints were 1p13/21 (six cases), 7q32/34 (five
      cases), 2p16/21 and 19p13 (four cases each), 4q25/28, 6q15/21 and 12q22/23 (three
      cases each). In two cases, a translocation between band 19q13 and band 14q11 or
      14q32 was found. This finding may indicate that an unknown oncogene in 19p13 is
      activated by juxtaposition next to a T-cell receptor or immunoglobulin gene in
      14q11 or 14q32, respectively. In eight cases each, total or partial monosomy 4 or
      6 was present suggesting that tumor suppressor genes in 4q or 6q play a role in
      tumor development in Hodgkin's disease. Moreover, the aberrant clones lacked the
      Y-chromosome in men and the second X-chromosome in women in eight out of nine and
      in two out of three cases, respectively. Although different cell populations,
      especially T cells, showed mitotic activity in unstimulated short term culture,
      combined immunophenotyping and karyotyping unequivocally demonstrated that CD30
      and CD15 positive Hodgkin and Sternberg-Reed cells represented the chromosomally
      aberrant clones.

PMID- 8289503
TI  - Quantifying chromosome changes and lineage involvement in myelodysplastic
      syndrome (MDS) using fluorescent in situ hybridization (FISH).
AB  - A simplified technique for fluorescent in situ hybridization (FISH) was used to
      investigate the prevalence of chromosomally abnormal clones in 13 cases of
      myelodysplastic syndrome (MDS). Biotinylated centromeric probes for chromosomes
      7, 8, 12 and X, as well as painting probes for chromosomes 7 and 11, were applied
      to air-dried bone marrow smears stored from 6 to 23 months. Nine of the cases had
      been previously karyotyped, and five of these demonstrated normal karyotypes
      which were confirmed by FISH. The remaining four cases showed different
      chromosome changes. One case of sideroblastic anemia with chronic lymphocytic
      leukemia showed minor clones with either monosomy 12 (12% of cells) or
      tetraploidy (15% of cells) by FISH, whereas metaphase cytogenetics had
      demonstrated trisomy 12 in 20% of cells, with no evidence of tetraploidy. Another
      case which had been previously karyotyped was found to have a t(7;11) in 90% of
      cells while only 10% of cells were shown by FISH to contain this translocation.
      Monosomy 7 was demonstrated by FISH in a case of refractory anemia (RA), while
      trisomy 8 was found in a case of RA with excess blasts in transformation (RAEB
      T), and in both of these cases the aneuploid clone was present in eosinophils as
      well as in erythroid and granulocytic precursors but not in lymphocytes or
      histiocytes, thereby demonstrating the value of FISH for identifying the affected
      cell lineage.

PMID- 8289504
TI  - Acute leukemia treated with intensive chemotherapy in patients with a history of
      previous chemo- and/or radiotherapy: prognostic significance of karyotype and
      preceding myelodysplastic syndrome. Groupe Francais de Cytogenetique
      Hematologique (GFCH)
AB  - The prognostic significance of karyotype and of a preceding myelodysplastic
      syndrome (MDS) was evaluated in 57 patients with acute leukemia (AL) treated with
      intensive chemotherapy. All patients had a history of previous chemo- and/or
      radiotherapy for a neoplastic disease. Acute nonlymphocytic leukemia (ANLL) was
      diagnosed in 49 patients, six patients suffered from acute lymphatic leukemia
      (ALL) and one patient from biphenotypic and undifferentiated AL, respectively.
      Chromosomal aberration rate was 91%. In 54% of the patients, simple or specific
      chromosomal anomalies with not more than three cytogenetic defects were found,
      such as t(8;21), t(15;17), inv(16), t(9;11) and t(4;11). Only 37% of the patients
      had a karyotype highly characteristic of sAL with more than 4 structural
      cytogenetic defects, and/or -5, 5q-, -7, 7q-. This unusual distribution of
      cytogenetic defects in these patients is undoubtedly due to patient selection,
      since only patients who received aggressive chemotherapy were included in this
      study. 25 patients had previously been diagnosed as having MDS. Presence or
      absence of a preceding MDS and karyotype were predictive parameters for
      achievement of complete remission (CR). CR was obtained in 47% of the patients
      with normal karyotype or simple aberrations, but only in 24% of the patients with
      complex anomalies (p = 0.09). Patients without a prior MDS had a higher CR rate
      (53%) than patients with a preceding MDS (20%) (p = 0.02). CR rate was highest in
      patients with a normal karyotype or simple aberrations without previous MDS
      (56%), compared to those with complex anomalies and a prior MDS (14%) (p = 0.02).
      We conclude that, from a clinical point of view, AL in the former patients should
      be considered as de novo AL and not as secondary, therapy-related AL and that
      therapeutic nihilism is no longer justified in these patients.

PMID- 8289505
TI  - Does IL-2 receptor expression and secretion in chronic B-cell leukemia have a
      role in down-regulation of the immune system?
AB  - Recent evidence of cell membrane expression of interleukin-2 receptors (IL-2R) by
      malignant B cells in hairy cell leukemia (HCL) and B-chronic lymphocytic leukemia
      (B-CLL) has lead to speculation that growth factors, such as IL-2, may play a
      role in the pathophysiology of these diseases. However, to date, it is not clear
      that IL-2 is a consistent growth factor in vitro or in vivo for malignant B
      cells. What then is the potential significance of membrane IL-2R on the malignant
      B-cell membrane? Laboratory analysis indicates that the malignant cells are the
      source of elevated serum levels of soluble Tac protein (sIL-2r alpha) in both
      diseases. Indeed, these cells spontaneously secrete sIL-2R alpha into culture
      medium. We speculate that the presence of an expanding mass of malignant B cells
      possessing high and low affinity membrane IL-2R may contribute significantly to
      the associated immunodeficiency seen in B-CLL. In particular, it is the cell
      associated high affinity IL-2R that have the greatest potential for reducing the
      levels of free IL-2 available to normal immune cells.

PMID- 8289506
TI  - Altered expression of the retinoblastoma gene product in human high grade non
      Hodgkin's lymphomas.
AB  - The retinoblastoma gene (RB) is a growth suppressor gene on the human chromosome
      13q14. It encodes a 105 kDa phosphoprotein (p105), with DNA-binding capacity.
      P105 is thought to be involved in cell cycle control. Inactivation of RB is
      responsible for the development of retinoblastomas and occurs frequently in
      osteosarcomas and small cell lung cancer. In this study we looked at the RB
      structure and expression in cell lines and primary lymphoma samples from patients
      with high grade non-Hodgkin's lymphoma (NHL). Forty five primary high grade NHL,
      the B-lymphoblastoid cell line IM-9 and the NHL cell line WSU-NHL were studied
      for RB structure by Southern blotting and for RB-expression by Northern blotting,
      Western blotting and immunocytochemistry. In all experiments freshly
      cryopreserved material was used. Southern and Northern experiments were performed
      with the 0.9 kb and 3.8 kb RB-cDNA probe. For the detection of p105 two different
      anti-p105-monoclonal antibodies were used in immunocytochemistry and Western
      blotting experiments. No RB mRNA and no p105 could be found in IM-9 cells. Twenty
      six high grade NHL samples (58%) showed no p105 expression. In the subgroup of
      centroblastic lymphomas 16 out of 21 and in Burkitt's lymphomas five out of eight
      showed no p105-expression. P105 expression is absent in 58% of high grade NHL,
      particularly in centroblastic and Burkitt's lymphomas, suggesting that
      inactivation of RB may play a crucial role in the pathogenesis of high grade NHL.

PMID- 8289507
TI  - [Surgical treatment combined with radiotherapy and chemotherapy in an unselected
      population of patients with malignant glioma].
AB  - BACKGROUND: Malignant gliomas are tumors of bad prognosis with a mean survival of
      12 months. In the present report 74 patients diagnosed of malignant glioma were
      studied with the following aims: 1) evaluate how many could receive combined
      radiotherapy (RT) and chemotherapy (BCNU) treatment following surgery and 2)
      analyze whether the patients treated presented a survival similar to that
      described in the literature. METHODS: The records of 74 patients operated on for
      malignant glioma between 1987-1990 and consecutively included in a protocol of
      treatment with RT and BCNU were reviewed. RESULTS: Out of the total of 74
      patients, 29 (39%) were considered evaluable. The medians of progression free
      interval and survival were of 10 and 16 months, respectively in these patients.
      Forty-five (61%) patients could not fulfill the protocol mainly because of
      tumoral progression prior to completion of RT and severe post surgical
      complications. The evaluable patients were significantly younger (p = 0.004) and
      tumoral exeresis wider (p = 0.0003) than in those who were not evaluable.
      CONCLUSIONS: Most of the patients operated on for malignant glioma may not
      receive treatment considered as standard, principally due to tumor progression in
      the first weeks following surgery and the presence of severe post surgical
      complications.

PMID- 8289508
TI  - [Projections of the impact of the smoking habit on the health of the Spanish
      population and on the potential benefits from its control].
AB  - BACKGROUND: Smoking continues to be an important public health problem in Spain.
      With the aim to know some of the health care consequences derived from the
      evolution of this habit in the Spanish population and to anticipate the health
      care benefits which would be a result of intervention on the same the estimations
      of mortality related with smoking and its control in the next few decades were
      predicted. METHODS: Mathematic models of simulation of the effects derived from
      changes in the prevalence of smoking based on the techniques of attributable
      risk, the multiplicity of the diseases involved and the time of reversal of the
      risk of death following health care intervention were used. RESULTS: In absence
      of intervention on smoking the number of total deaths by the causes under
      consideration will, in general, increase, from 1987 to 2020. The reduction of 40%
      in the prevalence of smoking in adult Spanish smokers over a period of 8 years
      (1992-2000) would potentially decrease the number of cardiovascular deaths by
      6,035, deaths by COPD by 394 and the deaths by malignant tumors studied in the
      year 2020 by 5,237. By the year 2020 the effects of intervention would, in
      general, be completely manifest. A part of this reduction of mortality would
      translate in a gaining of 57,323 real years of life in the year 2020. These
      benefits are also appreciable, although lesser, in the previous years from the
      beginning of intervention. CONCLUSIONS: Smoking will continue to be an important
      public health problem in Spain in the future. The health care benefits which may
      be derived from correct application of effective control programs of the same
      would be appreciable.

PMID- 8289509
TI  - [Changes in the pancreatic and respiratory functions in cystic fibrosis. The
      influence of the time of the evolution of the disease].
AB  - BACKGROUND: Cystic fibrosis is the most frequent congenital disease in Caucasian
      and is transmitted by recessive autosomic inheritance. It is characterized by
      affection of different glands of exocrine secretion, particularly the pancreas
      and the lung. The aim of this study was to analyze the degree of alteration of
      pulmonary and pancreatic exocrine function in a group of patients with cystic
      fibrosis in relation to the time of disease evolution. METHODS: Twenty-one
      patients between 9 and 31 years of age were studied; 11 with an evolution of
      lower than or equal to 158 months and 10 with an evolution of higher than 158
      months (median of the total patients). To study pancreatic exocrine function the
      BT-PABA test immunoreactive serum trypsin test were used. To evaluate respiratory
      function FEV1, FVC, FEV1/FVC ratio and PaO2 were used. RESULTS: The results
      obtained demonstrated that in the group with a lower time of evolution the
      diagnosis had been carried out at earlier ages (17 +/- 17 months versus 84 +/- 60
      months; p = 0.002) and presented a significantly more altered pancreatic exocrine
      function (BT-PABA: 13 +/- 12% versus 35 +/- 23%; p = 0.013). However, respiratory
      function was altered in the group with longer time of evolution (FEV1: 68 +/- 20%
      versus 36 +/- 23%; p = 0.003; FVC: 74 +/- 9 versus 52 +/- 25%; p = 0.013;
      FEV1/FEV: 77 +/- 19 versus 50 +/- 9%; p < 0.001; PaO2: 84 +/- 16 versus 58 +/-
      11%; p < 0.001). CONCLUSIONS: Pancreatic exocrine function is most intensely
      affected in patients diagnosed with cystic fibrosis at earlier and with shorter
      times of evolution while patients who have the longest time of evolution and who
      were diagnosed later in life presented greater changes in respiratory function.

PMID- 8289510
TI  - [Vitamin C: its current therapeutic applications].

PMID- 8289511
TI  - [The toxicological risks in textile airbrushing].

PMID- 8289512
TI  - [The importance of calcium in the diet for blood pressure regulation].

PMID- 8289513
TI  - [A man of 35 with gingivorrhagia and spontaneous hematomas].

PMID- 8289514
TI  - [The impact of AIDS on the increase in premature mortality in the city of
      Barcelona].

PMID- 8289515
TI  - [Splenic infarcts without venous thrombosis in the course of chronic
      pancreatitis].

PMID- 8289516
TI  - [Acute brucellosis, pancytopenia and bone marrow hypoplasia].

PMID- 8289517
TI  - [Is AIDS increasing or decreasing?].

PMID- 8289518
TI  - [HTLV-I and transfusions].

PMID- 8289519
TI  - [The efficacy of the prevaccinal detection of anti-HBc in hepatitis B vaccination
      programs].

PMID- 8289520
TI  - [Spanish scientific production in biomedicine and health. A study via the Science
      Citation Index (1986-1989)].
AB  - BACKGROUND: There is no detailed information on the scientific production in
      biomedicine from the perspective of the centers which make up the National Health
      Care System. Nor has any analysis on productivity by specialties compared with
      that of other countries of the European Community (EC) been carried out. METHODS:
      The methodology used and the global results of a study performed from biomedical
      investigation documents indexed in the SCI from 1986 to 1989 and signed by a
      Spanish health care center are presented. Quantitative and qualitative indicators
      (Narin index, impact factor [IF], mean IF per specialty, expected and observed IF
      as well as denominators [PIB, number of inhabitants per area, cost and number of
      personnel of the centers]). RESULTS: Twelve thousand seven hundred and six
      documents were studied of which 66.7% were journal articles and 13.5% were
      studies carried out in cooperation with foreign countries. The biomedical
      production was 41.5% of all the Spanish scientific investigation collected in the
      SCI in the same period and represented 3.82% of the contribution of all the
      biomedical investigation of the EC. Universities were responsible for 46% of the
      documents analyzed followed by hospitals with 39%. The autonomic communities of
      Madrid (32%) and Catalonia (26%) have the most productivity principally in
      hospitals, followed by Andalucia (10%) and Valencia (7%). The subject matters of
      greatest production were biochemistry, and molecular biology (14.7%),
      pharmacology and pharmacy (7.6%), neurosciences (6.8%) and microbiology (5.7%).
      Qualitative analysis showed that despite the investigation in some subject areas
      being carried out in journals with an IF higher than the world mean, the
      citations received by the studies are lower than expected. CONCLUSIONS: Despite
      the growth in Spanish biomedical production, Spain only occupies seventh place in
      the EC. Madrid and Barcelona notably concentrate on biomedical investigation from
      the hospital network. The relativization of the data describes the existence of
      other noteworthy geographic areas not outside the university. The ever greater
      diffusion of the publications contrasts with the citations received for the
      studies which may be the result of phenomena related with the quality of the
      studies and/or the recognition of the publications signed by Spanish authors.

PMID- 8289521
TI  - [The evaluation of hospital readmissions in the internal medicine service].
AB  - BACKGROUND: The aim of the study is determine the frequency of hospital
      readmission rate at an internal medicine department in a Community Hospital. We
      want to verify such a variables there are been associated with the readmission
      rate. METHODS: 870 patients were analyzed to repeated admissions to the hospital
      in a period of one year. The general independent variables and the complications
      were classified. We compared them with the calculation of the odds ratio (OR) in
      a bivariate and multivariate analysis. RESULTS: The readmission rate was about
      15.9% (CI: 13.7-18.3). The male patients (OR = 1.8 [CI 1.2-2.7]) and the great
      mortality (OR = 2.1 [CI 1.2-3.5]) were variables of great significance. Chronic
      obstructive pulmonary disease and malignant tumors of lung and pleura--as main
      diagnosis at discharge--correlated with readmissions. CONCLUSIONS: Evaluation of
      hospital readmissions is an indicator to be studied.

PMID- 8289522
TI  - [Changes in the spectrum of the diseases in patients hospitalized with HIV
      infection].
AB  - BACKGROUND: Infections in subjects with HIV-1 infection are a frequent cause of
      hospital admission. Knowledge of the entities which most often motivate
      hospitalization may aid in designing the most appropriate diagnostic and
      prophylactic strategies. The causes of hospital admission in individuals with
      risk practices for HIV-1 infection attended in a Department of Infectious
      Diseases in Madrid over a period of 4 years were analyzed. METHODS: The records
      of the patients admitted from 1989 to 1992 were retrospectively reviewed. The
      principal and associated diagnoses which led to hospitalization were considered.
      The admissions of the two years were compared. RESULTS: Bacterial pneumonias were
      the principal cause of hospitalization in the 2 years studied. Forty-five percent
      of the infections leading to hospital admission were not included among those
      defining AIDS. Tuberculosis was the most frequent opportunistic infection.
      Admissions due to pulmonary pneumocystosis, tuberculosis, toxoplasmosis,
      esophageal candidiasis and Kaposi's sarcoma decreased from 1989-1992. To the
      contrary, disseminated Mycobacterium avium complex infection and systemic
      infection by cytomegalovirus significantly increased over the same period. The
      incidence of other diseases such as endocarditis or leishmaniasis remained
      stable. More than half of the diseases were diagnosed in association with another
      entity during the same admission. Likewise, an increase in atypical forms of
      infections thus making diagnosis and treatment more difficult was observed. The
      first cases of multiresistant tuberculosis, all of rapidly fatal evolution, were
      identified in 1992. Mean hospital stay increased 30% and the rate of mortality
      was of 9% in 1989 and rose to 20% in 1992. CONCLUSIONS: The spectrum of
      infections which led to hospital admission of patients with HIV-1 infection has
      significantly modified over the last 4 years being related with the
      generalization of prophylactic medication for some opportunistic infections, the
      improvement of certain diagnostic techniques and more frequent ambulatory
      treatment of some diseases. The mean length of stay and hospital mortality have
      increased in the HIV+ population.

PMID- 8289523
TI  - [The clinical laboratory of the future and hospital research].

PMID- 8289524
TI  - [Striatocapsular infarct in a young patient with heterozygous familial
      hypercholesterolemia and Klinefelter's syndrome].
AB  - Familial hyperlipidemia has received little attention as a possible cause of
      stroke in young patients. Some recent studies have demonstrated that lipoprotein
      (a) is a key factor for atherogenesis in familial hypercholesterolemia.
      Hypogonadism may also contribute to the elevation of serum lipids, but their
      influence as a risk factor for stroke is still less understood. A 34-year-old
      patient with heterozygous familial hypercholesterolemia presented with a left
      pure motor hemiparesis secondary to a right striatocapsular infarction.
      Arteriography showed atherosclerotic lesions in both internal carotid arteries.
      High levels of cholesterol, cLDL, apo B, and lipoprotein (a) were found. Clinical
      signs of hypogonadism were present and the karyotype led to the diagnosis of
      Klinefelter's syndrome (47,XXY). The early clinical course was excellent, and the
      levels of serum lipids were normalized with diet, lipid-lowering drugs and
      androgens. The importance of hyperlipidemia as a risk factor for stroke in the
      young, specially when it occurs in the context of familial hypercholesterolemia
      with elevated lipoprotein (a) levels, as well as the possible contribution of
      hypogonadism to the development of accelerated atherosclerosis in young patients,
      are discussed upon.

PMID- 8289525
TI  - [The application of cytofluorometry to solid tumors for measuring DNA and the S
      phase].

PMID- 8289526
TI  - [A cost-effectiveness analysis of treatment with antiendotoxin monoclonal
      antibodies in gram-negative sepsis].

PMID- 8289527
TI  - [Gangliosides and the Guillain-Barre syndrome].

PMID- 8289528
TI  - [Hyperpotassemic paralysis: a rare complication of Addison's disease].

PMID- 8289529
TI  - Challenges and opportunities for technology assessment in medical informatics.
      Report of a MEDINFO '92 workshop.
AB  - Technology assessment in medical informatics is an emerging area. One of the
      recommendations of a joint IMIA-ISTAHC working conference (1990) was that this
      area should be further explored, e.g. by a special session at MEDINFO '92 and by
      a dedicated working group. The MEDINFO '92 workshop 'Challenges and opportunities
      for technology assessment in Medical Informatics' addressed these
      recommendations. It aimed to set the scene for a possible IMIA-ISTAHC working
      group. Prior to the workshop a questionnaire was distributed. This paper gives an
      overview of workshop and questionnaire results.

PMID- 8289530
TI  - Assessment of health information technology: which questions for which systems?
      Proposal for a taxonomy.
AB  - After a brief description of the main domains of application of medical
      informatics, a typology of questions to be assessed, and of the involved actors,
      is presented. Dimensions of technology assessment include techniques, medical and
      health efficacy, economics, sociology, and law and ethics. Barriers to evaluation
      are analysed. They include barriers related to the domain complexity, human
      motivation and methodological barriers. Finally categories of solutions and
      research areas are suggested.

PMID- 8289531
TI  - An approach for the evaluation of software engineering environments in medicine.
AB  - This article examines several criteria for the evaluation of software engineering
      environments (SEE) in medicine. The study is restricted to the evaluation of the
      SEE itself, not of its by-products which are the medical applications developed
      with the SEE. Basic principles for an evaluation methodology are presented. They
      consist in determining the evaluation objectives and judging a SEE according to
      criteria which are grouped into three broad categories--functional, generic and
      environmental. Each category reflects a particular domain of evaluation of the
      SEE. Methods of measurement and questions highlighting these specific areas are
      mentioned. Criteria are extracted from the list of objectives that follows the
      HELIOS European AIM project of the Commission of the European Communities.
      Special emphasis is drawn on the criteria for which the medical specificity and
      usefulness of a SEE can be approach. For this purpose a method of measurement of
      such appropriateness is proposed.

PMID- 8289532
TI  - Challenges and opportunities for technology assessment in medical informatics.
      Case study: PACS.
AB  - In this paper the basic steps of cost-effectiveness analysis (CEA) are applied in
      the evaluation of picture archiving and communication systems (PACS). The
      exercise demonstrates that evaluations of PACS have been technology-orientated,
      rather than problem-orientated. Moreover, many of the potential benefits of the
      system have been insufficiently investigated. Assessment based on the analysis of
      the bottlenecks in the film-based system alone appears to be quite inaccurate, as
      shown by the diverging outcomes of early assessment results. The development of
      PACS has reached a state in which the first clinical experiences are being
      collected. This provides an opportunity to test postulated costs and benefits.
      Moreover it may provide a better insight into the future potential of the
      technology. Experimenting with PACS is expensive. Hence, we should work together
      in evaluation, in order to benefit as much as possible from each other's
      experiences.

PMID- 8289533
TI  - Converting a rule-based expert system into a belief network.
AB  - The theory of belief networks offers a relatively new approach for dealing with
      uncertain information in knowledge-based (expert) systems. In contrast with the
      heuristic techniques for reasoning with uncertainty employed in many rule-based
      expert systems, the theory of belief networks is mathematically sound, based on
      techniques from probability theory. It therefore seems attractive to convert
      existing rule-based expert systems into belief networks. In this article we
      discuss the design of a belief network reformulation of the diagnostic rule-based
      expert system HEPAR. For the purpose of this experiment we have studied several
      typical pieces of medical knowledge represented in the HEPAR system. It turned
      out that, due to the differences in the type of knowledge represented and in the
      formalism used to represent uncertainty, much of the medical knowledge required
      for building the belief network concerned could not be extracted from HEPAR. As a
      consequence, significant additional knowledge acquisition was required. However,
      the objects and attributes defined in the HEPAR system, as well as the conditions
      in production rules mentioning these objects and attributes, were useful for
      guiding the selection of the statistical variables for building the belief
      network. The mapping of objects and attributes in HEPAR to statistical variables
      is discussed in detail.

PMID- 8289534
TI  - On the use of a hospital information system in evaluating clinical care: a case
      report.
AB  - In this paper we describe, as an example, how we obtained the information needed
      to evaluate a newly introduced protocol for ordering X-rays for ankle trauma
      patients. Extensive use was made of available data and facilities of the hospital
      information system (HIS). Procedures for collecting the required additional data,
      which were not recorded in the HIS but were needed to evaluate the protocol, were
      embedded in the current medical and administrative routine of the emergency room.
      These additional data were also stored in the HIS. Periodically all data were
      downloaded to a personal computer to analyse the impact of using the protocol on
      quality of care and costs. In total 1241 patients entered the study, and for 1149
      patients a complete dataset was obtained. The sensitivity and specificity of the
      protocol at the threshold value which was used during the initial study period
      was 0.77 and 0.80. The reduction in the number of ankle X-rays due to the
      protocol was significant when compared with a strategy of ordering an X-ray for
      every ankle trauma patient visiting the emergency room.

PMID- 8289535
TI  - Limits to diagnostic accuracy.
AB  - This paper explores the limits to computer-aided medical diagnosis. A specific
      application area (the diagnosis of abdominal pain of suspected gynaecological
      origin) is chosen, and the factors limiting the accuracy of computer programs are
      investigated by means of a simulation model which has been shown previously to
      generate realistic cases. The model is used to generate arbitrarily large
      training and test sets. The results suggest that, while statistical dependencies
      exist amongst symptoms and signs, there is little to be gained by taking
      interactions into account. However, failure to record all possible observations
      does limit diagnostic accuracy significantly. The results suggest that near
      optimal diagnostic accuracy (75-80%) can be obtained with a training set size of
      10(5) cases simply by applying Bayes' theorem with the usual assumption of
      conditional independence.

PMID- 8289536
TI  - Optical memory card applicability for implementing a portable medical record.
AB  - The implementation of portable record based on laser card technology is discussed
      in terms of data structures for quick access and software tools to reinforce
      security and confidentiality as required by medical data. Experimental results
      from a field test with a laser card technology are reviewed with regard to
      implementation in a large-scale and public information system. An efficient data
      structure is described for storage purposes, and some proposals are put forward
      to secure stored data.

PMID- 8289537
TI  - [Medical diagnosis at university hospitals. Able to compete also on the open
      market].

PMID- 8289538
TI  - [The ADEL reform--deteriorated care at nursing homes].

PMID- 8289539
TI  - [Surfactant therapy--no simple truths].

PMID- 8289540
TI  - [Laboratory medicine and shrinking resources].

PMID- 8289541
TI  - [Unfortunate formulation in LB (a drug index) about asthma in pregnancy].

PMID- 8289542
TI  - [Is dental scaling hazardous?].

PMID- 8289543
TI  - [P-marked--why not a resource?].

PMID- 8289544
TI  - [Patient information and anamnesis are important in dental treatment].

PMID- 8289545
TI  - [Continuous screening and treatment of teenage scoliosis is recommended].

PMID- 8289546
TI  - [Fatal cases of asthma in the 1-34 year age group should be reported!].

PMID- 8289547
TI  - [Cancer. The value of early diagnosis: partly a myth?].

PMID- 8289548
TI  - [Malnutrition in elderly patients. An overlooked phenomenon in Swedish health
      care].

PMID- 8289549
TI  - [What is myocardial infarct? Quality assurance based on mortality figures is
      misleading if the diagnostic criteria are varying].

PMID- 8289550
TI  - [Advertisements in the journal Lakertidningen--progress and curiosities during
      the last 90 years].

PMID- 8289551
TI  - [Philip Sandblom: artist of medicine, analyzer of art. Pain gives depth and
      dimension to life].

PMID- 8289552
TI  - [Nawal el Saadawi, a physician from Cairo. Her novel is her weapon in the fight
      for liberation of women].

PMID- 8289553
TI  - [Methods of working in modern rehabilitation].

PMID- 8289554
TI  - [A newly discovered blood coagulation disorder. Resistance to activated protein C
      as a cause of thrombosis].

PMID- 8289555
TI  - [Adrenoleukodystrophy. A disease of current interest and many aspects].

PMID- 8289556
TI  - [The Medical Products Agency on prevention of osteoporosis: estrogen reduces the
      risk of fractures in certain women].

PMID- 8289557
TI  - [Warning against routine use of heart surgery. Safety and quality are at risk].

PMID- 8289558
TI  - [Regular spinal check ups of school children should continue].

PMID- 8289559
TI  - [Myth and reality about trauma at a county hospital].

PMID- 8289560
TI  - [Last comment on cholesterol].

PMID- 8289561
TI  - [Anorexia nervosa: clinical trials should be conducted only on children and
      adolescents].

PMID- 8289562
TI  - [The future role of psychiatry. A society-oriented discipline?].

PMID- 8289563
TI  - [Adults with corrected heart defects. After-care and follow-up requires high
      competency].

PMID- 8289564
TI  - [The number of adults with congenital heart defects is increasing. Who will take
      care of them?].

PMID- 8289565
TI  - [More respect for the family members. Study of patients and their relatives in
      psychiatric care].

PMID- 8289566
TI  - [Criticism of psychiatric care. An analysis is necessary for understanding the
      reason of mistrust].

PMID- 8289567
TI  - [The man behind the method: Wilhelm Conrad Rontgen. A reluctant recipient of the
      Nobel Prize].

PMID- 8289568
TI  - [Aids to the handicapped. Prescriptions, testing and use].

PMID- 8289569
TI  - [The surgeon before the altar. Richard Selzer sees an officiant in the
      physician's coat].

PMID- 8289570
TI  - [New guidelines on research ethics from CIOMS (Council for International
      Organizations of Medical Sciences). A good example of balancing autonomy,
      benefits and human rights].

PMID- 8289571
TI  - [Increased inspection of blood banks].

PMID- 8289572
TI  - [Many reasons against special treatment in self-inflicted injuries].

PMID- 8289573
TI  - Effect of ketamine-anesthesia on N-methyl-D-aspartate-induced activation of type
      I nucleus accumbens neurons.
AB  - Extracellular single-unit recording and microiontophoretic techniques were used
      to determine the effects of ketamine-anesthesia on N-methyl-D-aspartate (NMDA)
      induced excitation of Type I nucleus accumbens neurons. NMDA increased the firing
      rate of most neurons in this preparation. Thus, it may be concluded that ketamine
      anesthesia does not result in blockade of central NMDA receptors. The excitation
      caused by NMDA was readily reversed in all cases by co-iontophoresis of MK 801,
      but was generally unaffected by coiontophoresis of ketamine. However, ketamine
      anesthesia did significantly increase the current levels necessary for, and
      limited the magnitude of, NMDA-induced activation of these cells (as compared to
      urethane-anesthetized rats), suggesting that ketamine is not without effect on
      NMDA-receptors in vivo.

PMID- 8289574
TI  - Platelet paroxetine binding and fluoxetine pharmacotherapy in posttraumatic
      stress disorder: preliminary observations on a possible predictor of clinical
      treatment response.
AB  - Recent open clinical trials have found the selective serotonin reuptake inhibitor
      (SSRI) fluoxetine to be beneficial in the treatment of posttraumatic stress
      disorder (PTSD) symptoms. We have reported previously that the binding of a newer
      SSRI, paroxetine, to blood platelets is decreased in PTSD patients compared to
      normal control subjects. In the current study, pretreatment platelet paroxetine
      binding data were analyzed for ten Vietnam combat veterans who were treated
      clinically with fluoxetine for PTSD, diagnosed on the basis of the Structured
      Clinical Interview for DSM-III-R. Specific binding of 3H-paroxetine is reported
      in terms of the dissociation constant (Kd) and the maximum density of binding
      sites (Bmax). Based on our previous findings we hypothesized that decreased
      platelet 3H-paroxetine binding would be associated with positive therapeutic
      response to subsequent treatment with fluoxetine. Global clinical improvement
      ratings, conducted blind to the biochemical data, were used to separate patients
      into five maximal responders and five partial responders. The results indicated
      that maximal responders had lower pretreatment Kd values (p = .016) and a trend
      toward lower pretreatment Bmax values (p = .075) than the partial responders.
      These preliminary findings may warrant further study of platelet SSRI binding as
      a possible predictor of SSRI treatment response in PTSD patients.

PMID- 8289575
TI  - Excitatory amino acid receptors: a gallery of new targets for pharmacological
      intervention.
AB  - The excitatory amino acids (EAAs) L-glutamate and L-aspartate are the most
      abundant amino acids in brain and play a number of roles in maintaining neuronal
      function. Among these are their use as protein constituents, as key intermediates
      in ammonia metabolism, and as precursors for other neurotransmitters. Given the
      widespread distribution of EAA-containing neurons, these transmitters are likely
      to be involved in virtually all central nervous system functions, with
      abnormalities in neurotransmission contributing to the symptoms of a host of
      neurological and psychiatric disorders. Because of the importance of EAAs in
      maintaining the functional integrity of the central nervous system, efforts are
      underway to design agents capable of regulating the activity of these
      transmitters for therapeutic gain. Inasmuch as potential side effects preclude a
      generalized modification of this system, strategies must be found to alter EAA
      neurotransmission in selected brain regions. In this regard, pharmacological data
      suggest several functionally distinct EAA receptors, a finding confirmed by
      cloning studies which hint at an even larger family of sites. Moreover, it
      appears that some excitatory amino acid receptor complexes are composed of
      interacting sites which orchestrate receptor function, and there is evidence that
      EAA receptors may influence the activity of one another. Thus, there appear to be
      numerous sites that can be targeted to selectively modify excitatory amino acid
      neurotransmission in brain. Besides the agonist recognition site for each
      receptor subtype, other targets include regulatory subunits, ion channels and
      components of receptor-coupled second messenger systems.

PMID- 8289576
TI  - Exercise causes oxidative damage to rat skeletal muscle microsomes while
      increasing cellular sulfhydryls.
AB  - The physiological and biochemical demands on contracting muscle make this tissue
      particularly susceptible to molecular and cellular damage. We looked at membrane
      structures in cardiac and skeletal muscle and in erythrocytes for exercise
      induced lipid peroxidation. These tissues were removed from each of the rats used
      in this study. We also examined and compared the effects of exercise on the redox
      status of blood plasma, erythrocytes and cardiac and skeletal muscle from the
      same rats. We used a swim stress protocol to exercise the rats to exhaustion.
      Some form of chemical modification or oxidative damage to membranes was observed
      in all of the tissues tested. Cardiac muscle microsomes from exercised rats
      exhibited increased malondialdehyde and decreased phospholipid (control, 249.1 vs
      exercised, 120.6 nmols phospholipid/mg protein). Skeletal muscle microsomes
      showed decreased sulfhydryls, decreased phospholipid (control, 1,276.9 vs
      exercised, 137.7 nmols phospholipid/mg protein), increased malondialdehyde and
      greater protein crosslinking after exercise. Erythrocyte membranes also exhibited
      exercised-induced protein oxidation. However, the total cellular sulfhydryl
      content remained the same in erythrocytes and cardiac tissue but increased in
      blood plasma (control, 10.8 vs exercised, 24.7 mumols SH/dl plasma) and skeletal
      muscle after exercise. We conclude that exercise profoundly effects membrane
      structures. The body compensates for this lipid peroxidation and protein damage
      by increasing total cellular sulfhydryls in blood plasma and skeletal muscle
      which would aid in repair of the damaged membranes.

PMID- 8289577
TI  - Cannabinoid receptors in rat brain areas: sexual differences, fluctuations during
      estrous cycle and changes after gonadectomy and sex steroid replacement.
AB  - Cannabinoid effects on brain dopaminergic activity vary as a function of gonadal
      status. In this work, we examined whether these variations might be due to sex
      steroid-dependent differences in brain cannabinoid receptors (CNr). Four
      experiments were done: (i) male versus females; (ii) females at each stage of the
      ovarian cycle; (iii) estradiol (E2) and/or progesterone (P)-replaced
      ovariectomized (OVX) females; and (iv) testosterone (T)-replaced orchidectomized
      males. The density of CNr in the medial basal hypothalamus fluctuated in females
      during the estrous cycle. The density was higher in diestrus and decreased in
      estrus. This parameter did not change after ovariectomy and E2 replacement.
      However, P increased the density of CNr when administered to OVX rats acutely
      treated with E2, but not administered alone or after chronic E2 treatment. In the
      striatum, the affinity of CNr was slightly higher in males than females, with no
      changes in density. Ovariectomy increased the affinity of CNr, which normalized
      only after administration of acute E2. Interestingly, the high affinity values
      observed in this area after P alone or combined with E2, corresponded to low
      densities as compared with intact females. In the limbic forebrain, the affinity
      for the cannabinoid ligand was also higher in males than females with no changes
      in density. Affinity was also higher in diestrus and lower in estrus, whereas
      density was unchanged. Ovariectomy decreased CNr density. A normal situation was
      found after administration of acute E2 or P alone, whereas chronic E2 markedly
      increased the density of CNr as compared with both intact and OVX females.
      Interestingly, this latter increase was prevented by coadministration of P.
      Orchidectomy did not affect CNr density, but administration of T produced a
      marked decrease. In the mesencephalon, the density and affinity of CNr was higher
      in males than females. Administration of P to OVX rats produced opposite effects,
      increasing the density when administered alone and decreasing it when
      administered to acute E2-replaced OVX rats. In summary, these results reveal the
      existence of subtle, sometimes more pronounced, sex dimorphisms, fluctuations
      along the ovarian cycle and changes after gonadectomy and sex steroid replacement
      in CNr density and affinity in certain brain areas. This supports the hypothesis
      of possible sex steroid-dependent differences in the sensitivity of certain
      neuronal processes to cannabinoid treatment.

PMID- 8289578
TI  - Chronic nicotine reverses age-associated increases in tail-flick latency and
      anxiety in rats.
AB  - The chronic consumption of low doses of nicotine in drinking water for two years
      consistently increased the sensitivity of rats to a nociceptive thermal stimulus
      (tail-flick test), but reduced aversiveness in the elevated plus-maze test,
      relative to the responses of age-matched controls in these tests. The responses
      of aged nicotine-consuming rats were indistinguishable from those of young adult
      rats that did not receive nicotine. To determine whether these effects were due
      to a nicotine-induced retardation of age-related changes, young adult rats were
      similarly treated with nicotine for three months and similar changes in the tail
      flick latency and performance in the plus-maze test were observed during nicotine
      consumption. These changes were reversed following withdrawal from nicotine. It
      is concluded that the maintenance of circulating low levels of nicotine (and/or
      its metabolites) increased the nociceptive sensitivity of the rats and reduced
      their aversions in the plus-maze test regardless of their age.

PMID- 8289579
TI  - Protracted high-dose interferon gamma therapy for chronic experimental
      nephropathy.
AB  - This study focused on the utility of interferon gamma (IFN gamma) as an anti
      fibrotic drug in renal experimental fibrosis; the nephropathy was induced by two
      doses of Adriamycin (ADR) in 20 Sprague Dawley rats, 10 of which were randomly
      assigned to receive IFN gamma (45,000 UI) on alternate day for 16 weeks. At the
      end of the follow up, ADR rats treated with IFN gamma developed massive
      proteinuria, slight renal insufficiency, and presented diffuse
      glomerulosclerosis, tubulo interstitial infiltration and fibrosis. No difference
      was found in the composition of tubulo-interstitial infiltrates, mainly
      consisting in CD4+T lymphocytes with a minor component of CD8+T cells, in
      comparison with rats treated with ADR alone. These observations demonstrate the
      inefficacy of a protracted high-dose treatment with IFN gamma in chronic
      experimental nephropathy with interstitial fibrosis.

PMID- 8289580
TI  - Changes in dopamine metabolism in rat forebrain regions after cessation of long
      term fluoxetine treatment: relationship with brain concentrations of fluoxetine
      and norfluoxetine.
AB  - We examined the effects of repeated administration of the selective serotonin
      uptake inhibitor (SSRI) fluoxetine (Flx) (5, 10, or 15 mg/kg i.p., twice daily
      for 21 days) on brain and plasma concentrations of the parent drug and its active
      desmethyl metabolite, norfluoxetine (NFlx), in rats during the 21-day regimen as
      well as after cessation of drug treatment. We also measured dopamine (DA) levels
      in 2 midbrain regions (the striatum, St and nucleus accumbens, NAc) in rats
      killed 1-14 days after the last dose. NFlx concentrations in plasma and brain
      were ten times higher than those of Flx during the period of drug treatment.
      Although Flx accumulated more markedly in the rat brain than NFlx, it disappeared
      completely from plasma and brain after treatment stopped, while NFlx persisted up
      to Day P7. Chronic Flx treatment caused a persistent decrease in brain DA levels
      of -60% to -70% in St and NAc; this lasted for 7-14 days after cessation of
      treatment, depending on the dose used. The levels of DA metabolites decreased by
      20-40%, and, except for 3-MT, tended to overshoot during the recovery period. Our
      data suggest that the long-term inhibition of DA neurons after cessation of Flx
      treatment parallels the inhibition previously observed for 5-HT neurons. Thus,
      besides blocking 5-HT uptake, Flx is likely to also inhibit in vivo DA uptake in
      forebrain regions, following prolonged administration.

PMID- 8289581
TI  - Opioid mu receptor subtypes (possibly mu 1 and mu 2) revealed by morphine-induced
      antinociception vs endothelin-1 in recombinant inbred CXBK mice.
AB  - Morphine was administered intracerebroventricularly to normal or recombinant
      inbred CXBK (mu-opioid receptor deficient) mice and antinociception was
      determined against two different stimuli. Morphine-induced antinociception
      against acetylcholine was strain-dependent, whereas against endothelin-1 it was
      not. The antinociception was mediated via opioid mu receptors (blocked by beta
      FNA, but not naltrindole, ICI 174,864 or nor-BNI) through separate pathways, one
      naloxonazine-sensitive and the other naloxonazine-insensitive. Taken together,
      these results appear to demonstrate supraspinal morphine-induced antinociception
      through distinct subtypes of the mu opioid receptor, supporting the possibility
      of novel subtype-selective therapeutic agents with greater separation between
      analgesia and side-effects or physical dependence. Furthermore, the methodology
      described herein provides model systems for the in vivo screening of such agents.

PMID- 8289582
TI  - The acute actions of growth factors in smooth muscle systems.
AB  - Work over the past six to eight years has established that mitogenic polypeptides
      such as epidermal growth factor-urogastrone (EGF-URO) or platelet-derived growth
      factor (PDGF), commonly referred to as 'growth factors', can have rapid (seconds
      to minutes) regulatory actions in a variety of smooth muscle systems. With EGF
      URO as a prototype example, this article describes three distinct smooth muscle
      response paradigms, two of which (type A and type B) comprise a rapid (seconds to
      minutes) increase in muscle tension) and one of which (type C) is characterized
      by an EGF-URO-mediated reduction in sensitivity to other agonists. The quite
      distinct signal transduction pathways for the three types of response paradigms
      are outlined, and the marked tissue and species variation in the types of smooth
      muscle responses that can be observed, even for a single growth factor agonist,
      are summarized. The article also illustrates that G-protein-coupled vasoactive
      agents such as angiotensin-II and vasopressin, which can act as 'growth factors'
      in cultured cell systems, can also work via tyrosine kinase pathways to cause
      contraction in some of the same intact smooth muscle preparations that contract
      in response to growth factors such as EGF-URO. Attention is drawn to the fact
      that many so-called 'growth factors', quite apart from stimulating cell division
      and differentiation, may in many instances act as rapid localized
      paracrine/autocrine regulators of tissues such as smooth muscle. It is also
      pointed out that some of the tyrosine kinase-modulated signal pathways usually
      associated with the mitogenic action of 'growth factors' may be involved not only
      in the rapid effects of agents such as EGF-URO in smooth muscle but also in the
      contractile actions of G-protein-linked agonists.

PMID- 8289583
TI  - Investigation into vanadate-induced potentiation of smooth muscle contractility
      in the rabbit isolated ileum.
AB  - The action of sodium orthovanadate (Na3VO4) on spontaneous mechanical activity of
      the longitudinal muscle was investigated in isolated segments of rabbit distal
      ileum. Vanadate (0.3-1000 microM) concentration-dependently enhanced the
      amplitude of phasic contractions (pendular movements) and caused the muscle tone
      to slightly increase at the highest concentrations. Both these effects were
      mimicked by the Ca2+ channel activator BAY K 8644 (10-1000 nM). Vanadate- and BAY
      K 8644-induced potentiation of mechanical activity was antagonized by the Ca2+
      entry blocker nifedipine (3 nM). In Ca(2+)-free, K(+)-depolarized preparations,
      vanadate (100 microM) failed to contract the musculature, but potentiated the
      contractile response to applied calcium (CaCl2: 30-300 microM). The action of
      vanadate was similar to that of BAY K 8644 (3 nM) and was antagonized by
      nifedipine (0.1 nM). These results suggest that extracellular calcium is required
      for vanadate-induced smooth muscle excitation which, at least in part, appears to
      arise from facilitation of calcium influx through voltage-dependent Ca2+
      channels.

PMID- 8289584
TI  - The novel anticonvulsant lamotrigine prevents dopamine depletion in C57 black
      mice in the MPTP animal model of Parkinson's disease.
AB  - The effect of the novel anticonvulsant Lamotrigine (LTG) was studied on 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopamine depletion in C57BL/6
      mouse brain. Whole brain dopamine levels were measured by HPLC-ED 2 days after
      treatment with MPTP (15 mg/kg s.c.). While LTG alone had no direct effect on
      dopamine levels at two hours or two days after treatment, MPTP induced dopamine
      depletion was significantly less in mice pretreated with LTG (approximate ED50: 6
      mg/kg). LTG (38 mg/kg) was shown to completely protect against dopamine depletion
      when given 1 or 2 hours prior to MPTP administration. The effect of LTG (38, 100
      mg/kg) on MPTP toxicity was compared to the effects of the anticonvulsants
      phenytoin (67 mg/kg), carbamazepine (156 mg/kg), and riluzole (33 mg/kg) and the
      Ca++ channel blocker nicardipine (0.1 mg/kg). Only phenytoin and LTG showed
      significant protection against MPTP. Results suggest LTG prevents MPTP induced
      dopamine depletion via a novel mechanism.

PMID- 8289585
TI  - Involvement of gamma-aminobutyric acid in the stimulatory effect of
      metoclopramide on gastrointestinal motility.
AB  - The involvement of gamma-aminobutyric acid (GABA) in the mechanism of action of
      metoclopramide (MCP) on gastrointestinal (GI) tract was investigated employing
      guinea-pig myenteric plexus longitudinal muscle preparations. MCP induced a
      concentration dependent enhancement of electrically induced twitch responses of
      the myenteric plexus and this effect was further intensified by arecaidine and L
      2, 4-diaminobutyric acid (L-DABA; GABA uptake inhibitors) and ethylenediamine
      (EDA; GABA releasing agent). The facilitatory effect of MCP was reduced by 3
      mercaptopropionic acid (3-MPA; GABA synthesis and release inhibitor) and after
      GABA desensitization but remained unchanged after bicuculline methiodide, a
      specific GABA receptor antagonist. The MCP induced contraction of the
      unstimulated preparation was also reduced after GABA desensitization and EDA
      without affecting responses to exogenous acetylcholine (ACh). The study indicates
      that GABA plays a role in the facilitatory effect of MCP on both stimulated and
      unstimulated preparations of guinea pig myenteric plexus.

PMID- 8289586
TI  - Blood luteinizing hormone and prolactin concentrations in response to naltrexone
      challenge: studies on rats with diabetes induced by different doses of
      streptozotocin.
AB  - Opiate system involvement in diabetes induced by three different doses of
      streptozotocin (STZ; 40, 50, and 60 mg/kg body weight [BW]) was studied by
      monitoring luteinizing hormone (LH) and prolactin (PRL) levels as a response to
      naltrexone (Nalt) administration. After four weeks of diabetes a marked decrease
      in BW, as well as severe hyperglycemia and increased blood urea nitrogen (BUN)
      levels were found. The rats, whose diabetes was induced by 50 mg/kg of STZ,
      exhibited the highest amount of blood glucose (P < 0.05, compared with the 40
      mg/kg induced group) and BUN levels (P < 0.004 compared with the other two
      groups) and BW loss. The normal response to Nalt, which is expressed by elevation
      of plasma LH and decreased plasma PRL levels was observed only in the low-dose
      STZ (40 mg/kg BW) diabetes-induced group, while in the other two diabetic groups
      (50 and 60 mg/kg BW) there was no significant change in plasma LH and PRL as a
      result of the Nalt challenge. Presensitization of the endogenous opioid receptors
      by morphine in normoglycemic (control) and "low-dose diabetic" rats (40 mg/kg BW
      of STZ), presented a clear difference between the two. Morphine pretreatment
      inhibited LH response to Nalt in the low-dose, STZ-induced diabetic rats, while
      no effect of morphine pretreatment on LH response to Nalt could be recorded in
      the normoglycemic group. Thus it can be concluded that in STZ-induced diabetes,
      plasma glucose and BUN levels do not reflect the neuroendocrine injury observed
      when monitored by LH and PRL secretion in response to Nalt challenge.
      Supersensitization of the opioid receptors before the Nalt challenge may increase
      the ability to reveal neuroendocrine system impairment.

PMID- 8289587
TI  - Erythrocyte Ca2+ handling in the spontaneously hypertensive rat, effect of
      vanadate ions.
AB  - Cytosolic Ca2+ concentration ([Ca2+]i) and 45Ca2+ influx were investigated in
      erythrocytes from conscious spontaneously hypertensive rats (SHR) and their
      normotensive controls Wistar-Kyoto (WKY). [Ca2+]i was evaluated with fura-2 and
      intra- and extra-cellular calibration parameters were compared. Irrespective of
      the calibration parameters used, erythrocyte [Ca2+]i was always significantly
      higher in SHR than in WKY and Wistar rats (by 25 and 40%, p < 0.01 and 0.001). A
      rise of the external Ca2+ concentration from 1 to 2 mmol/l increased less [Ca2+]i
      in SHR than in WKY erythrocytes (17 vs 37%, p < 0.01). SHR erythrocytes
      incorporated more 45Ca2+ than those from WKY, with an initial rate of 45Ca2+
      uptake higher by 57% than that of WKY erythrocytes (p < 0.05). Vanadate ions,
      after corrections of their quenching effect on red cell and fura-2 fluorescence
      signals, increased [Ca2+]i by 19% in WKY erythrocytes (p = 0.05), but did not
      modify the SHR values. They also increased 45Ca2+ accumulation and the initial
      rate of 45Ca2+ influx in WKY erythrocytes only (p < 0.01). This study indicates
      that, when compared to WKY rats, erythrocytes from SHR are characterized by
      higher [Ca2+]i values, higher initial rate of Ca2+ influx and low sensitivity to
      vanadate ions.

PMID- 8289588
TI  - Differences in potency of big endothelin-1-induced pressor action in rat isolated
      perfused mesenteric artery, hindquarter and lung.
AB  - We compared the pressor response to endothelin-1 (ET-1) with that of big
      endothelin-1 (big ET-1) in mesenteric arteries, hindquarters and lungs of rats.
      In these three preparations, both peptides caused a concentration-dependent
      increase in the perfusion pressure. The ratio of big ET-1 concentration to ET-1
      concentration needed for causing the same pressor action is different between
      organs; i.e., a mesentery >> a hindquarter > or = a lung. Exposure to
      phosphoramidon, a metalloproteinase inhibitor, significantly suppressed the
      pressor response to big ET-1, in a similar fashion. This suppression is likely to
      be due to the inhibition of phosphoramidon-sensitive endothelin converting
      enzyme, since the inhibitor does not suppress an action of ET-1. Apparently there
      is a difference in potency for phosphoramidon-sensitive vasoconstriction of big
      ET-1 between organs and presumably regional differences in the functional
      phosphoramidon-sensitive conversion of big ET-1 in vasculatures.

PMID- 8289589
TI  - Expression of 11 beta-hydroxysteroid dehydrogenase mRNA in rat vascular smooth
      muscle cells.
AB  - The enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD) converts corticosterone
      to the inactive 11-dehydrocorticosterone in the rat. The bioactivity of 11-HSD,
      expressed as the percentage conversion of 3H-corticosterone to 3H-11
      dehydrocorticosterone, was 13.7 +/- 0.4% in rat vascular smooth muscle cells
      (rVSMC). Cells treated with 100 nM dexamethasone (Dex) showed a 1.4-fold (p <
      0.05) increase in 11-HSD activity. Insulin (100 microM) decreased 11-HSD activity
      by 0.8-fold (p < 0.05). Expression of 11-HSD mRNA was also confirmed in rVSMC by
      Northern blot analysis. Dexamethasone increased and insulin decreased the levels
      of 11-HSD mRNA in parallel with the increase in bioactivity. Vascular smooth
      muscle cells express 11-HSD activity; the access of corticosterone to vascular
      smooth muscle receptors may be modulated by the enzyme.

PMID- 8289590
TI  - Myocardial effects of experimental neoplastic disease.
AB  - The purpose of this study was to determine the effects of the 7288ctc Morris
      hepatoma on heart size and performance. Hearts from tumor bearing and control
      animals were perfused in the working configuration one to three weeks post
      implantation. As tumor growth progressed there was an inverse linear relationship
      between tumor size and heart weight. When intrinsic heart work (defined as the
      product of the cardiac output and peak systolic pressure) was assessed in vitro
      over a range of physiologic preloads, significant differences were found between
      tumor-bearing and non-tumor-bearing animals. The hearts from the tumor-bearing
      animals (tumor weight 10-20 grams) developed only 76% of the heart work of
      control animals at maximal left atrial filling pressure (25 cm H2O). Hearts
      excised from rats with tumor masses from 30-65 grams developed 43% of the
      myocardial work as controls at the same (25 cm) preload. At the time of sacrifice
      resting blood pressures, blood glucose, insulin, and tumor necrosis factor (TNF)
      levels were similar in both groups. Blood from tumor bearing animals were
      negative for both aerobic and anaerobic bacteria. The data suggests that the
      decrements in cardiac size and performance are independent of several vectors
      known to influence heart size and performance and occur in the absence of
      detectable bacteremia.

PMID- 8289591
TI  - Function of melatonin in thermoregulatory processes.
AB  - Accumulated information shows that, besides its role in the timing of seasonal
      reproduction, melatonin also plays an important role in seasonal thermoregulatory
      adjustments of animals including torpor and hibernation. Furthermore, melatonin
      has a crucial role in circadian thermoregulatory adjustments of body temperature
      (Tb). Melatonin appears to send signals to the preoptic area of anterior
      hypothalamus (PoAH) where it adjusts the set point of Tb consistent with the
      metabolic rate of the animal. This new function for melatonin as a transducer
      mediating information about energy balance has been suggested in this review.
      Melatonin also adjusts the activity of the biological clock in vertebrates.

PMID- 8289592
TI  - Effects of naturally occurring flavonoids on mitogen-induced lymphocyte
      proliferation and mixed lymphocyte culture.
AB  - In this investigation, 34 structurally different flavonoids including derivatives
      of chalcone, flavanone, flavan-3-ol, flavone, flavonol, and their glycosides were
      evaluated for in vitro suppression of mitogen-induced lymphocyte proliferation
      and mixed lymphocyte culture from mouse spleen. Flavonoids, mainly derivatives of
      flavone and flavonol, clearly demonstrated the suppressive effects on lymphocyte
      proliferation at higher than 10(-6) M depending on the structures of flavonoid
      molecules, although their suppressive activities were less than that of
      cyclosporin A or prednisolone. Various glycosidic substitutions to A- and/or C
      ring of the flavonoid aglycones were found to eliminate the suppressive
      activities of their aglycones, regardless of sugar compositions and positions of
      substitutions. In concanavalin A-induced lymphocyte proliferation, derivatives of
      flavone and flavonol having 2,3-unsaturation and at least 1 hydroxyl group showed
      the suppressive activity. In lipopolysaccharide-induced lymphocyte proliferation,
      only myricetin was active among flavonoids tested at the concentrations up to 10(
      5) M. In mixed lymphocyte culture, some derivatives of flavone and flavonol with
      2,3-unsaturation were active and especially flavone derivatives showed the higher
      suppressive activities than those of the flavonol derivatives.

PMID- 8289593
TI  - Urethane anesthesia reverses the protective effect of noncompetitive NMDA
      receptor antagonists against cocaine intoxication.
AB  - The present experiments examined whether pretreatment with the noncompetitive N
      methyl-D-aspartate (NMDA) receptor antagonists, MK-801 and dextrorphan, could
      antagonize cocaine-induced convulsions and lethality in conscious Sprague-Dawley
      (SD) rats and whether urethane anesthesia alters the observed interactions.
      Conscious, restrained male SD rats received continuous i.v. infusions of cocaine
      hydrochloride (1.25 mg/kg.min) until convulsions and death occurred. Cocaine
      doses of 21.2 +/- 1.8 and 29.5 +/- 2.5 mg/kg caused convulsions and death,
      respectively, in saline treated rats (n = 8). Convulsions were absent in MK-801
      (1 mg/kg, i.v.; n = 8) pretreated rats; the lethal cocaine dose was 44.0 +/- 2.7
      mg/kg (p < 0.05). In contrast, urethane anesthesia (1.2 g/kg, i.p.) decreased the
      dose of cocaine required to cause toxicity, compared to that in saline controls
      (24.8 +/- 0.8 mg/kg, n = 13), in MK-801 (2.0 +/- 0.3, n = 7; p < 0.01) and in
      dextrorphan mg/kg, n = 13), in MK-801 (2.0 +/- 0.3, n = 7; p < 0.01) and in
      dextrorphan (25 mg/kg, i.v.; 13.1 +/- 1.4, n = 6; p < 0.01) pretreated rats.
      Pressor responses with little change in heart rate were evident during cocaine
      infusion in vehicle pretreated rats. Bradycardiac responses were noted to cocaine
      in groups following NMDA receptor blockade. Reversal of the pressor response to
      cocaine was noted in MK-801 pretreated animals, while dextrorphan pretreatment
      moderated cocaine-induced increases in blood pressure. Ventilatory support
      protected against cocaine lethality in urethane anesthetized rats, indicating
      that respiratory failure is the proximate cause of death with cocaine infusion.
      However, artificially ventilated rats, pretreated with MK-801, were more
      sensitive (lethal cocaine dose, 76.6 +/- 8.0 mg/kg, n = 5) than vehicle
      pretreated rats (129.4 +/- 15.8 mg/kg, n = 6), indicating that MK-801 may
      increase both the respiratory and the cardiac toxicity of cocaine in urethane
      anesthetized rats. Interactions between NMDA receptors and cocaine are modified
      by urethane anesthesia.

PMID- 8289594
TI  - Immunomodulation by morphine in Plasmodium berghei-infected mice.
AB  - The effect of morphine on immunomodulation and host defense have been
      investigated during Plasmodium berghei infection in BALB/c mice. A single low
      (5.0 mg/kg) subcutaneous dose of morphine strongly suppressed (sometimes
      completely eliminated) the parasitaemia, whereas a high dose (80.0 mg/kg) exerted
      mild potentiating effect. Mice treated with the low dose showed a significant (p
      < 0.05) increase in the total number of circulating leukocytes, the number (pool
      size) of peritoneal macrophages, and the phagocytic activity of peritoneal
      macrophages, in vitro. Conversely, in mice treated with the high dose, all these
      parameters were diminished. Silica (3.0 mg/mouse), administered intravenously,
      abrogated the morphine-induced protective effects but did not affect its
      potentiation of the infection. Naloxone pretreatment (4.0 mg/kg) completely
      blocked the protective effects of morphine, suggesting the mediation via naloxone
      sensitive opiate-receptors; paradoxically, it did not affect the potentiating
      effects. These observations indicate that morphine exerted a dose-dependent,
      biphasic effect on the course of P. berghei infection in mice, apparently by
      modulating the macrophage-mediated protective mechanisms.

PMID- 8289595
TI  - Characterization and physiological variation in prostaglandin, prostacyclin and
      thromboxane synthesis by corpora lutea, non-luteal and uterine tissues during
      pseudopregnancy in the rabbit.
AB  - To determine if luteal as well as uterine prostaglandin production is associated
      with luteal regression, the conversion of (14C) arachidonic acid into
      prostaglandin (PG) F2 alpha, PGE2, PGD2, prostacyclin (measured as its stable
      metabolite 6-keto-PGF1 alpha) and thromboxane (measured as its stable metabolite
      TXB2) was characterized and measured in microsomes from the uterus, corpora lutea
      and nonluteal tissue of the rabbit on days 8, 12 and 15 of pseudopregnancy. PGF2
      alpha production was increased on day 15 compared to days 8 or 12 of
      pseudopregnancy in corpora lutea and in the uterus. In uterine microsomes, 6-keto
      PGF1 alpha production was also elevated on day 15. No significant changes in the
      production of PGF2 alpha, TXB2 or PGD2 were observed with uterine or luteal
      microsomes. Arachidonic acid metabolism by microsomes from nonluteal tissue was
      not significantly different on any day examined. These results suggest that
      intraluteal, as well as uterine PGF2 alpha production may contribute
      physiologically to the final phase of luteal regression.

PMID- 8289596
TI  - Localization of heat shock protein in orbital tissue from patients with Graves'
      ophthalmopathy using in situ hybridization.
AB  - We studied the cellular localization of heat shock protein 70 (HSP70) synthesis
      in human orbital tissue from patients with Graves' ophthalmopathy(GO) before and
      after immunosuppressive therapy. Synthesis was detected using in situ
      hybridization techniques. In a specimen from a GO patient in active phase, strong
      expression of HSP70 mRNA was detected in infiltrating lymphocytes as well as in
      fibroblasts. HSP70 mRNA was also detected in orbital tissue fibroblasts from GO
      patients following treatment, but not in control specimens. HSP70 expression in
      the orbital tissue of GO patients may be important in mediation of the immune
      process.

PMID- 8289597
TI  - Effect of simvastatin treatment on plasma apolipoproteins and hepatic
      apolipoprotein mRNA levels in the genetically hypercholesterolemic rat (RICO).
AB  - The effects of long-term treatment with simvastatin on plasma lipoproteins,
      plasma apolipoproteins, and on hepatic apolipoprotein gene expression were
      evaluated in genetically hypercholesterolemic (RICO) rats. Simvastatin
      administration caused a decrease in plasma triglyceride and phospholipid
      concentrations. Plasma cholesterol concentration was not changed by simvastatin,
      but cholesterol distribution among plasma lipoproteins was altered. Plasma apo B,
      apo A-I, and apo A-IV concentrations were lowered by simvastatin treatment
      whereas plasma apo E concentration was not affected by this drug. In the liver,
      simvastatin treatment induced a significant decrease of apo E mRNA level but had
      no effect on apo B, apo A-I, and apo A-IV mRNA abundances. It appears that
      simvastatin may modify plasma apolipoprotein concentrations by influencing their
      hepatic synthesis at both pre- and posttranscriptional levels.

PMID- 8289598
TI  - Effects of capsaicin analogs on adrenal catecholamine secretion in rats.
AB  - To assess the relationship among the structure, pungency and thermogenic action,
      a series of capsaicin analogs with saturated acyl moieties (heptanoyl to
      eicosanoyl vanillylamide) were synthesized. Pungency of the compounds and the
      thermogenic action, which was examined by the potential of the compounds (655
      nmol/kg, i.v.) to enhance adrenal catecholamine secretion for 15 min in
      anesthetized rats, were compared. On the chain length of the acyl moieties of the
      analogs, nonanoyl to octadecanoyl vanillylamide caused strong adrenal
      catecholamine secretion, but heptanoyl vanillylamide and eicosanoyl vanillylamide
      caused weak or no response. Pungent analogs except heptanoyl vanillylamide and
      non-pungent analogs except eicosanoyl vanillylamide had strong potency to secrete
      adrenal catecholamine.

PMID- 8289599
TI  - The effect of a vitamin E-deficient diet on amino acid levels in the substantia
      nigra, striatum and hippocampus of rats.
AB  - The effects of a vitamin E deficiency diet for 15 days on amino acid
      concentrations have been studied in the substantia nigra, striatum and
      hippocampus of the rat. The substantia nigra showed an increase in glutamate and
      GABA and a decrease of tryptophan concentration compared with controls. In the
      striatum, aspartate and glycine decreased, no changes were found in the amino
      acid concentrations in the hippocampus. The substantia nigra and striatum showed
      opposite results-an increase and decrease of amino acids respectively. The
      increase of glutamate found in substantia nigra is particularly interesting as it
      may suggest possible links to degenerative processes. These results suggest that
      vitamin E could play a crucial role in substantia nigra degeneration and that the
      substantia nigra could be more sensitive to an oxidative stress than other brain
      structures.

PMID- 8289600
TI  - Meprin is predominantly involved in parathyroid hormone degradation by the
      microvillar membranes of rat kidney.
AB  - Hydrolysis of fragments of the C-terminal and mid-portions of parathyroid hormone
      (PTH) by a phosphoramidon-insensitive metallo-endopeptidase, previously purified
      by us from the microvillar membranes of rat kidney, and by the microvillar
      membranes of rat kidney themselves were investigated using a reverse-phase HPLC,
      and the amino acid sequences of each produced PTH metabolite were compared after
      their determination with an automated gas-phase protein sequencer. The results
      showed that both the purified microvillar endopeptidase and the microvillar
      membranes of rat kidney limited hydrolyzed human (h) PTH-(39-84) and hPTH-(39-68)
      mainly at peptide bonds flanked by a hydrophilic amino acid residue, where are
      characteristic for the purified microvillar endopeptidase but not for other known
      endopeptidase including endopeptidase 24.11. In addition, most of PTH metabolites
      generated by the microvillar membranes were insensitive to phosphoramidon and had
      amino acid sequences identical to those generated by the purified microvillar
      endopeptidase, indicating that these metabolites were produced by the enzyme
      integrated in the membranes. Since analysis of the N-terminal amino acid sequence
      of the purified microvillar endopeptidase revealed that it was structurally
      identical to rat meprin (EC 3.4.24.18), these results indicate that the purified
      microvillar endopeptidase or meprin is predominantly involved in PTH degradation
      by the microvillar membranes of rat kidney as an integral membrane protein.

PMID- 8289601
TI  - Assessing the clinician's use of computers.

PMID- 8289602
TI  - A medical informatics course as part of residency training in Canada.

PMID- 8289603
TI  - The quantitative basis for consensus.

PMID- 8289604
TI  - Guidelines for creating a simple database.
AB  - The advantage of using a simple flat file program is its simplicity and
      flexibility. The user has control over screen and report design; creating a
      database that meets the specific needs of a single department is easy and
      inexpensive. On the other hand, flat file programs have limitations. The main
      problem with Q&A is the need to duplicate data in two or more files. Other
      limitations are a result of the menu-oriented system, which requires compromises
      in report formatting and other areas. Database management systems are improving
      rapidly. Relational databases are becoming easier to use and can overcome many of
      the limitations of a flat file system. Flat file systems are becoming more
      enhanced and are beginning to look relational. Developing a system using a simple
      flat file approach allows the novice to identify and use information without
      conceptualizing a relational structure. Information can be entered and used
      quickly, with a better understanding of how everything works. Fewer things can go
      wrong and need fixing. Keeping your systems simple and following our other
      guidelines will allow you to use the computer as a tool to increase productivity.

PMID- 8289605
TI  - Low bone mineral density at axial and appendicular sites in amenorrheic athletes.
AB  - Amenorrheic athletes have low axial bone-mineral density (BMD, g.cm-2). We
      compared 12 amenorrheic and 9 eumenorrheic women athletes to determine whether
      athletes with amenorrhea have lower BMD in other skeletal regions, including
      weight-bearing lower limbs. BMD was measured by dual energy x-ray and single
      photon absorptiometry. Both groups had similar age, body mass, and exercise
      quantity. Women with amenorrhea missed 86.3 +/- 58.3 menstrual periods since
      menarche. BMD was lower in the amenorrheic vs eumenorrheic subjects for the
      lumbar spine (0.928 +/- 0.056 vs 1.050 +/- 0.110, P < 0.005), whole body (1.032
      +/- 0.05 vs 1.09 +/- 0.06, P < 0.05), most regions of the whole body (P < 0.05
      0.001), all areas of the proximal femur (P < 0.005), and at the femoral mid-shaft
      (1.333 +/- 0.109 vs 1.491 +/- 0.088, P < 0.005). No significant differences were
      detected at the mid-radius and tibial shaft. The best predictors of BMD were
      years of regular menstruation for lumbar spine; and years of amenorrhea for hip,
      femoral mid-shaft, and whole body. We conclude that low BMD in athletes with
      amenorrhea is not limited to the axial skeleton but is also present in other
      regions including appendicular weight-bearing bones.

PMID- 8289606
TI  - Mechanical loading regime and its relationship to bone mineral density in
      children.
AB  - This study tested the hypothesis that differences in mechanical loading regime
      was important when evaluating the potential role of physical activity on bone
      density in children. Seventeen children competing regularly in weight-bearing
      sports producing loads of at least 3 times body weight (Impact Load) were matched
      for race, gender, stage of puberty, body weight, and average daily training time
      with children involved in competitive swimming (Active Load). Bone mineral
      density (BMD) was measured using dual photon absorptiometry at the lumbar spine
      (L2-L4) and femoral neck (FN), Tanner staging was used to assess puberty, diet
      was evaluated based on 3-d dietary records from two occasions, and a
      questionnaire assessed average daily nonweight-bearing hours. There were no
      significant differences in age (13.2 +/- 0.4 and 12.6 +/- 0.4), height (154.9 +/-
      2.9 and 157.6 +/- 3.0), or weight (43.6 +/- 2.7 and 44.5 +/- 2.2) between Impact
      and Active Load groups. Impact Load children had significantly greater FN BMD
      (0.78 +/- 0.02) than Active Load children (0.72 +/- 0.02) and a tendency for
      greater BMD L2-L4; 0.70 +/- 0.03 and 0.66 +/- 0.03, respectively. These data
      indicate that children involved in sports producing significant impact loading on
      the skeleton had greater femoral neck bone density and a trend for greater spinal
      bone density, than children in sports producing loads to bone primarily through
      muscular contraction.

PMID- 8289607
TI  - Gastrointestinal problems as a function of carbohydrate supplements and mode of
      exercise.
AB  - The aim of the study was to examine prevalence and duration/seriousness of
      gastrointestinal (GI) problems as a function of carbohydrate-rich (CHO)
      supplements and mode of exercise. The relationship between GI problems and a
      variety of physiological and personal factors (age, exercise experience) was also
      examined. Thirty-two male tri-athletes performed three experimental trials at 1
      wk intervals, each trial on a different supplement: a conventional, semisolid
      supplement (S; 1.2 g CHO, 0.1 g protein, and 0.02 g fat.kg BW-1 x h-1); an almost
      isocaloric fluid supplement (F; 1.3 g CHO.kg BW-1 x h-1, no fat, no protein); and
      a fluid placebo (P). The 3 h of exercise started at 75% VO2max and consisted of
      alternately cycling (bouts 1 and 3) and running (bouts 2 and 4). GI symptoms were
      monitored by a questionnaire. Analysis of variance revealed that nausea lasted
      longer with P as compared with S (P < 0.05). Bloating lasted longer during bout 3
      with P as compared with F and S (P < 0.05). Accounting for confounding factors,
      most GI symptoms occurred more frequently and lasted longer during running than
      during cycling. Multiple regression analysis revealed significant relationships
      between nausea and urge to defecate, between an urge to defecate, GI cramps and
      flatulence, and between belching and side ache. From all other factors energy
      depletion, CHO malabsorption, exercise intensity, exercise experience, and age
      were significantly related to GI symptoms during the exercise.

PMID- 8289608
TI  - Fluid restriction prior to cycle exercise: effects on plasma volume and plasma
      proteins.
AB  - The purpose of this study was to test the hypothesis that changes in exercise
      intensity dominate the PV response to cycle exercise in the heat independent of
      the initial plasma volume (PV) and total circulating protein (TCP) content. The
      two experimental treatments (counterbalanced design) were performed by nine
      trained male cyclists (age = 23 +/- 1 yr, VO2peak = 63 +/- 4 ml.kg-1.min-1) in
      both a euhydrated (EU) and hypohydrated (HP, 24-h fluid restriction) state. Blood
      volume was measured (carbon monoxide dilution) 30 min prior to each test and
      subsequent changes in PV were calculated from serial venous blood samples using
      hematocrit and hemoglobin concentration. Following 20 min of seated rest in a
      warm environment (Tdb = 30 degrees C, 50-60% RH), each subject cycled in a semi
      reclining posture for 60 min at three successive intensities (60, 120, and 180 W
      for 20 min each, representing approximately 22, 37, and 53% VO2peak). Fluid
      restriction reduced (P < 0.05) body weight by 1.4 +/- 0.3 kg (1.8 +/- 0.4%), PV
      by 353 +/- 73 ml (8 +/- 2%), TCP by 20 +/- 7 g (7 +/- 2%), and elevated serum
      osmolality by 6 +/- 2 mOsm.kg-1 (2 +/- 1%). After 20 min of passive heat exposure
      (prior to exercise), TCP content remained lower (P < 0.05) in HP (17 +/- 5 g)
      compared with EU as PV increased (P < 0.05) in EU (222 +/- 27 ml) but not (P >
      0.05) in HP (122 +/- 35 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289609
TI  - Effects of skin blood flow and temperature on bioelectric impedance after
      exercise.
AB  - To examine the effects of increased skin blood flow (BFsk) and skin temperature
      (Tsk) on bioelectric impedance (BIA), 30 young males participated as subjects.
      All subjects underwent the following measurements: 1) BFsk and Tsk for the chest,
      biceps, thigh, and calf; 2) body composition using the BIA prediction equations
      and underwater weighting (UW); and 3) triceps skinfold (SFtri) thickness. After
      the baseline studies (M1) the subjects exercised for 30 min at approximately 83%
      of maximal heart rate. The above measurements were repeated immediately after
      exercise (M2), and at 1-h recovery from exercise (M3). Repeated measures ANOVA
      showed that mean Tsk and BFsk, and for the four measured sites were significantly
      increased from M1 to M2 (P < 0.05) and decreased from M2 to M3 (P < 0.05). These
      changes did not affect BIA measurement for resistance (R) and reactance between
      M1 and M2 (P > 0.05), and between M2 and M3 (P > 0.05). With regression analysis
      the following independent variables were identified as strong contributing
      factors for predicting fat-free mass (FFM): 1) SFtri and total body water for M1
      and M3; and 2) WT, SFtri, and Tsk of the chest for M2. Two FFM equations have
      little multicolinearity (M1 and M2), e.g., they have low root mean square errors
      (< or = 2.6 kg), very high values for R2 (> or = 0.94), and relatively low values
      for coefficient of variations (< or = 5.65%). Differences (P < 0.05) were
      observed between the UW method and the Lukasi equation for estimating FFM for M1
      and M3, but not for M2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289610
TI  - The effects of anabolic steroids on myocardial structure and cardiovascular
      fitness.
AB  - To determine the effects of anabolic steroids on myocardial structure, VO2max,
      and body composition, experienced age-matched male weight trainers (M age 26.5
      yr) who either used (U) (N = 11) or did not use (NU) (N = 13) anabolic steroids
      were evaluated. Steroid users were tested while off cycle (U-OFF) for at least 8
      wk, again at the peak (U-ON) of their subsequent cycle, and to the nonuser group
      of weight trainers. Echocardiographic measurements revealed significant
      differences in left ventricular (LV) mass (182.8 +/- 26.9 g vs 210.6 +/- 42 g; P
      < 0.05) and interventricular septum thickness (IVS) (10.3 +/- 1.2 mm vs 11.1 +/-
      1.2 mm; P < 0.05) between U-OFF and U-ON, respectively. NU measurements were also
      significantly different than U-ON for LV mass and IVS (186.5 +/- 36.2 g; P < 0.05
      and 9.3 +/- 1.2 mm; P < 0.05, respectively). LV diameter in diastole was
      significantly greater in U-ON (59.1 mm) than in NU (55.7 mm; P < 0.05). In
      addition, LV posterior wall thickness in diastole was greater in U-ON compared
      with NU (11.2 mm vs 9.5 mm; P < 0.05). VO2max values for both user groups were
      significantly lower than those for NU (U-OFF = 41.0 +/- 4.5 ml.kg-1.min-1, U-ON =
      41.0 +/- 5.7 ml.kg-1.min-1, and NU = 50.2 +/- 6.4 ml.kg-1.min-1; P < 0.05).
      Despite these morphological changes within the myocardium, there were no
      concomitant increases in shortening fraction.

PMID- 8289611
TI  - Canine cardiac sarcoplasmic reticulum is not altered with endurance exercise
      training.
AB  - To investigate the effect of exercise training on calcium movements by isolated
      cardiac sarcoplasmic reticulum (SR), mongrel dogs either remained sedentary (S)
      or were exercise-trained (E) via running for a period of 8-10 wk. The trained
      state was confirmed by the increase in skeletal muscle citrate synthase activity
      and decreases in submaximal exercise heart rates in the E group but not in the S
      dogs. The properties of isolated cardiac SR were identical between the groups.
      The variables tested included ATP-dependent calcium transport and calcium
      stimulated ATPase activity. Importantly, there was no difference in spontaneous
      calcium release which occurred after peak ATP-dependent calcium accumulation was
      reached. Calcium release from passively loaded vesicles induced by calcium and
      ionophore also did not differ in the SR isolated from the E dogs. The change in
      the affinity of the SR Ca ATPase for calcium after the addition of the polyanion,
      heparin, was similar in both groups, indicating that the regulation of calcium
      stimulated ATPase activity by the SR protein, phospholamban, is not modified by
      exercise training. We conclude that exercise training of 8-10 wk duration does
      not alter the calcium handling properties of cardiac SR isolated from mongrel
      dogs.

PMID- 8289612
TI  - The response of leukocyte subsets and plasma hormones to interval exercise.
AB  - Aerobic exercise has an established role in modulation of peripheral leukocyte
      concentrations. However, the effects of intense interval exercise, as employed by
      athletes in a range of sports, has been given little attention. Eight trained
      male athletes of mean age (SD) = 31.5 (4.5) yr; VO2max = 64.3 (3.8) ml.kg-1.min-1
      undertook an intense interval exercise protocol (treadmill running) to
      exhaustion. Subjects completed an average of 15.6 1-min efforts. The protocol
      produced a biphasic leukocytosis: an initial (immediately posttest) leukocytosis
      resulting from mobilization of lymphocytes (CD3+, CD4+, CD8+, CD16+/56+,
      CD3+HLA/DR+) (all P < 0.01), with the later (6 h) leukocytosis resulting from
      mobilization of granulocytes and monocytes (both P < 0.01). This protocol
      modified significantly the peripheral blood concentration of the hormones
      cortisol (both total and free), norepinephrine, DHPG, and dopamine (all P <
      0.01). Modulation of peripheral leukocyte subsets induced by interval exercise
      correlated with both the number of exercise efforts performed and the concomitant
      changes in peripheral hormone concentrations. Sustained alterations in plasma
      catecholamine levels in the posttest period may have important metabolic and
      immunological implications for athletes undertaking regular interval training.

PMID- 8289613
TI  - Oxygen cost of treadmill running in 24-month-old Fischer-344 rats.
AB  - The oxygen cost of treadmill running is well documented in young adult rats.
      However, to our knowledge there are no detailed reports concerning the oxygen
      cost of treadmill running in senescent rats. Young adult (4 months; N = 8) and
      senescent (24 months; N = 8) female Fischer-344 rats were tested for O2 cost of
      treadmill running. One-half of the animals tested in each age group had completed
      10 wk of endurance training. Oxygen cost of treadmill running, using a flow
      through system, was measured on a per minute basis from 7-10 min of each work
      bout and averaged. Separate work bouts were performed at 0%, 5%, and 10% grade at
      15, 20, 25, and 30 m.min-1. Oxygen cost of treadmill running for trained rats for
      all speeds and grades were not significantly different (P = 0.77) from untrained
      animals; thus, data were pooled for oxygen cost of running. Results revealed
      significantly lower (P < 0.05) VO2 (expressed as ml.kg-1.min-1) for senescent
      rats vs young adult rats rest and at all comparable treadmill grades and speeds
      except for 5% grade, 25 m.min-1 and 10% grade, 20 m.min-1. In addition, resting
      VO2 was significantly lower (P < 0.05) in old rats when compared with young rats.
      Thus, we conclude that the oxygen cost of treadmill running is lower for 24-month
      old rats than in 4-month-old rats except at higher work levels.

PMID- 8289614
TI  - A physiological comparison of forward vs reverse wheelchair ergometry.
AB  - The purpose of this study was to compare metabolic and cardiopulmonary responses
      for forward wheelchair ergometry (FOR) and reverse wheelchair ergometry (REV) at
      equal power outputs (PO) levels. Moderately active able-bodies (N = 21) subjects
      exercised at 3-min stages at PO levels of 15, 20, 25, and 30 W for each mode of
      ergometry. Oxygen uptake (VO2), pulmonary ventilation (VE), respiratory exchange
      ratio (RER), heart rate (HR), percent net mechanical efficiency (ME), revolutions
      per minute (RPM) and strikes per minute (SPM) were determined at each PO level.
      With the exception of RER, all the physiological responses (VO2, VE, and HR) were
      higher for FOR exercise (P < 0.05) than REV exercise. ME increased with PO and
      was higher (P < 0.05) for REV than FOR at each PO level. SPM values for the REV
      were lower (P < 0.01) by almost half of that for the FOR exercise, although RPM
      remained constant between modes during all four stages. In general, these data
      suggest that reverse wheelchair ergometry is physiologically more efficient than
      conventional wheelchair ergometry and should be studied further as an alternative
      method for wheelchair ambulation.

PMID- 8289615
TI  - The association between cycling experience and preferred and most economical
      cadences.
AB  - The purpose of this study was to compare 1) the preferred cadences and 2) the
      aerobic demand response to cadence manipulation of highly fit, experienced
      cyclists and equally fit noncyclists. Eight cyclists (C) and eight non-cyclists
      (NC) pedaled at 200 W under six randomly ordered cadence conditions (50, 65, 80,
      95, 110 rpm and preferred cadence) on a Velodyne trainer. The VO2 responses of C
      and NC to cadence manipulation were similar. Both groups displayed lower VO2
      values at lower cadences. VO2 differences between C and NC across cadences were
      not significant. Mean preferred pedaling cadence surprisingly was somewhat higher
      for NC (91.6 +/- 10.5 rpm) than C (85.2 +/- 9.2 rpm), but the difference was not
      significant. The most economical cadence was significantly lower for C (56.1 +/-
      6.9 rpm) than NC (62.9 +/- 4.7 rpm). Thus, cycling experience did not
      substantially influence preferred cadence nor economy during moderate intensity
      cycling by highly fit athletes. We speculate that preferred cadence and economy
      similarities between C and NC are associated with similarities in the dynamic
      muscular training of the groups.

PMID- 8289616
TI  - Effects of stair-climbing vs run training on treadmill and track running
      performance.
AB  - Physically active college age women were evaluated to determine the effects of 9
      wk of stair-climbing (Stairmaster Gauntlet) vs run training on 2414-m run time
      and treadmill measured aerobic capacity (VO2max) and submaximal physiological
      parameters. Subjects were randomly assigned to a stair-climbing (STAIR N = 11)
      (43.8 +/- 1.5 ml.kg-1.min-1) (mean +/- SEM) or run training (RUN N = 12) (44.2 +/
      1.8) group, training 4 d.wk-1 at 70-80% of maximum heart rate (MHR) for 30 min
      progressing to 85-90% MHR for 45 min. The STAIR group significantly increased (P
      < 0.01) their VO2max by 12% and decreased (P < 0.01) their 2414-m run time of
      12.8 min by 8%. The RUN group increased (P < 0.01) their VO2max 16% and decreased
      run time (P < 0.01) 11% from 13.1 min. Submaximal treadmill runs at the same
      speed and grade demonstrated significant decreases in %VO2max and % MHR (P <
      0.01) for both groups. The data support the use of stair-climbing exercise as an
      alternative mode to running with similar treadmill and running performance
      results subsequent to 9 wk of training.

PMID- 8289617
TI  - The optimal training load for the development of dynamic athletic performance.
AB  - This study was performed to determine which of three theoretically optimal
      resistance training modalities resulted in the greatest enhancement in the
      performance of a series of dynamic athletic activities. The three training
      modalities included 1) traditional weight training, 2) plyometric training, and
      3) explosive weight training at the load that maximized mechanical power output.
      Sixty-four previously trained subjects were randomly allocated to four groups
      that included the above three training modalities and a control group. The
      experimental groups trained for 10 wk performing either heavy squat lifts, depth
      jumps, or weighted squat jumps. All subjects were tested prior to training, after
      5 wk of training and at the completion of the training period. The test items
      included 1) 30-m sprint, 2) vertical jumps performed with and without a
      countermovement, 3) maximal cycle test, 4) isokinetic leg extension test, and 5)
      a maximal isometric test. The experimental group which trained with the load that
      maximized mechanical power achieved the best overall results in enhancing dynamic
      athletic performance recording statistically significant (P < 0.05) improvements
      on most test items and producing statistically superior results to the two other
      training modalities on the jumping and isokinetic tests.

PMID- 8289618
TI  - Evaluation of a shallow water running test for the estimation of peak aerobic
      power.
AB  - The purpose of this investigation was to assess the validity of a 500-yard
      shallow water run test to determine peak aerobic power (VO2peak) and to compare
      it with the commonly used 1.5-mile run test. Subjects included 15 men and 28
      women who completed two trials each of a 500-yard shallow water run test and a
      1.5-mile run and then completed a graded exercise test on a treadmill to
      determine VO2peak. Correlation coefficients with measured VO2peak were -0.89 and 
      0.80 for the 1.5-mile and 500-yard water runs, respectively. Multiple regression
      analyses revealed that prediction of VO2peak from 1.5-mile run time was
      significantly improved by including the 1.5-mile run peak HR (R2 = 0.82, SEE =
      3.52 ml.kg-1.min-1). Similarly, for the 500-yard water run test, percent body fat
      and height were significant additional predictors of VO2peak (R2 = 0.86, SEE =
      3.19 ml.kg-1.min-1). We conclude that the 500-yard shallow water run test,
      especially when used with the descriptive measures of percent body fat and
      height, can provide a reasonable estimate of an individuals' cardiorespiratory
      fitness classification. However, caution is advised when administering these
      tests in older populations or in those with multiple coronary risk factors.

PMID- 8289619
TI  - An application of mechanostat theory to research design: a theoretical model.
AB  - In this paper a theoretical model for research into the area of bone health is
      proposed. The model is based on the mechanostat theory of bone biology,
      originally proposed by Harold M. Frost, and is directed toward research in the
      area of osteoporosis. The mechanostat theory is briefly reviewed, including the
      concept of changes in minimum effective strain thresholds. Each of the model's
      five levels is then detailed, followed by discussion of their application to
      research design and interpretation. The proposed research model may provide a
      systematic approach to research design, and thereby a method to increase the
      current understanding of bone biology.

PMID- 8289620
TI  - Effect of time zone and game time changes on team performance: National Football
      League.

PMID- 8289621
TI  - 31P-MRS of quadriceps reveals quantitative differences between sprinters and long
      distance runners.

PMID- 8289622
TI  - [Acquired immunodeficiency syndrome (AIDS) in a rural milieu. Case of Dabou and
      its surroundings].
AB  - In the beginning, the rural zones had been considered as exempt from penetration
      by the HIV. During the early to the mid 1980's, AIDS prevalence rates ranged from
      1 to 7% in this rural area. The study of prevalence rates in the coastal region
      of the Ivory Coast shows an epidemic of catastrophic proportions developing at an
      alarming rate. Rates of over 15% (up to 21.9%) have been found. All of which
      demand the maintenance and further development of appropriate social and sanitary
      infrastructures able to match the needs of a rural population who from now on are
      faced at the edge of a human holocaust attributable to the AIDS virus.

PMID- 8289623
TI  - [Acquired immunodeficiency syndrome (AIDS): knowledge and fear of contagion in
      nursing students during their hospital training].
AB  - The authors report the transversal investigation results of 115 male and nurse
      students of Cotonou on their AIDS knowledge, AIDS prevention, and their attitudes
      toward HIV infected patients. 98% have a good knowledge of AIDS. 55% utilize
      condom. 77% give to their fear of contagion during their in Service training for
      the care of HIV infected patients. The authors conclude for AIDS education
      reinforcement in school of nursing.

PMID- 8289624
TI  - [Caudal anesthesia: experience at the University Hospital Center of Treichville.
      50 cases].
AB  - The above account concerns 50 cases of caudal anaesthesia with 2% plain lidocaine
      (i.e. without adrenaline), after a preliminary and a complementary general
      anaesthesia for surgical operations in the infra umbilical region not exceeding
      one hour in duration. The anaesthetic effect was as rapid as the recovery from
      it. The analgesic effect was excellent in 98% of cases. No per or post operative
      complications were observed with the employment of this technique. The authors
      recommend that this technique should be employed more frequently in day case
      pediatric surgery.

PMID- 8289625
TI  - [Study of weaning foods in infants in Brazzaville].
AB  - The authors have searched the characteristics of weaning for 400 children from 0
      to 24 months examined in mother and child health centre of Brazzaville. The study
      has revealed that the exclusive feeding to the breast is the predominant method
      (81.5%). The weaning paps utilized are in great part local (64.3%) but their
      preparation and their method of keeping them constitute a real problem. The
      sudden weaning has been observed in 87.2% of the cases. The recommended feeding
      square wasn't yet regarded so that the protidic foods were little consumed
      (44.0%) as well as protective foods too (50.4%).

PMID- 8289626
TI  - [Parasitological research conducted between 1982 and 1991 in a sample of Zinvie
      (Benin) residents].
AB  - The authors point out the frequency of intestinal parasitism in Zinvie (Benin).
      Out of 18,512 samples, 9,554 (51.60%) were found positive. The main parasites
      found were: Ankylostoma duodenale, Ascaris lumbricoides, Amoeba, Giardia lamblia.
      The authors underline the polyparaitism 16.75%.

PMID- 8289627
TI  - [Intestinal parasitoses in the south-eastern district of the Dominican Republic].
AB  - A prevalence test about parsitism in the South-East district of Dominique Island
      was carried out from 2 populations samples: some people preparing foods, and out
      patients in day care Centers. The parasites, the most frequently identified are:
      ankylostomae, ascaris and whipworms. The prevalence rate of parasitic infestation
      in this Island appears to be a suitable socio-economical development index.

PMID- 8289628
TI  - [Cholera in Benin (epidemic of 1991)].
AB  - Authors report on epidemiologic, bacteriology and therapeutic data related to
      1991 cholera outbreak in Benin in the general context of the 7th world pandemic.
      7474 cases were notified from all over the country. Vibrio cholerae 01, El Tor
      biotype, was identified in many patients stools and in the surroundings. Control
      measures implemented in this situation are described: early parenteral and mainly
      oral rehydration, antibiotic treatments for patients and contacts, systematic
      home control around cases, wells disinfection and general hygiene promotion,
      mobilization of the Civil Service Authorities and population education. Authors
      conclude that strict epidemiologic monitoring is necessary in epidemic
      circumstances as well as during endemo-sporadic period.

PMID- 8289629
TI  - [Cutaneous-pulmonary sarcoidosis. Diagnostic difficulties in the Black African
      milieu].
AB  - About a case of pulmonary and dermatologic manifestations of sarcoidosis, in a
      Black African patient, the authors emphasize the clinical polymorphism of
      sarcoidosis. They insist on the diagnostic criteria of sarcoidosis which are not
      at all specific of the disease but necessitate a compatible interpretation;
      particularly in Black Africa where leprosy, tuberculosis and many others
      granulomatous diseases are endemic.

PMID- 8289630
TI  - [Malaria indices, larval ecology and trophic activity of Anopheles mosquitoes in
      Djohong (Adamaoua, Cameroon) in the rainy season].
AB  - In Djohong in the wet season the prevalence of malaria is 17.5% for Plasmodium
      falciparum and 1.1% for Plasmodium malariae. In children 2 to 9 years of age the
      plasmodic index is 38.6% (mesoendemicity) for the children of the peasants and
      9.4% for those belonging to other socioeconomical groups. In infants less than 12
      months old, the plasmodic index is 9.3%, this relatively high rate corresponding
      to the high transmission period of the rainy season. Anopheles gambiae is the
      mosquito species most often found in the area (2/3 of the mosquitoes caught in
      the houses). The breeding sites in he surrounding of the houses are rainwater
      holes linked to human activity. At a larger distance from the houses, in the
      valley, the breeding sites are water holes borrowed for the retting of cassava
      tubercle or natural rock pools found in the basaltic shores of the Mbere river.
      The trophic activity of Anopheles gambiae and Anopheles funestus is high between
      0 and 4 hours a.m. In October the mean number of anopheline mosquitoes bites per
      night per inhabitant is 33 inside the houses and 7 outside.

PMID- 8289631
TI  - ["Keep in mind cutaneous amebiasis!" A case report in the Melen Hospital, Gabon].

PMID- 8289632
TI  - [Intra-muscular injections and post-injectional paralysis. 18 cases].
AB  - The study of 264 lower limbs paralysis recorded from 1988 to 1990 in 6
      Physiotherapy Centers in Madagascar showed that 66% has received prior intra
      muscular injections. Among those, 10.2% could be diagnosed as post injectional
      paralysis and quinine was responsible in 73%. Defining a national policy on the
      use of the intra-muscular injections, training medical workers and improving the
      access to oral and intra-rectal drugs could help to decrease the frequency of
      those complications spirochetes and other infections (43).

PMID- 8289633
TI  - [Galeazzi fracture. 9 cases in the orthopedic-traumatology service (Brazzaville
      Congo)].
AB  - The authors give an account of nine cases of Galeazzi fractures, observed on a
      four-year period (1987-1991). These uncommon and unstable injuries were treated,
      in all cases, by rigid osteosynthesis of the radius. The treatment of the distal
      radio-ulnar dislocation, depending on its importance, was K-wire stabilization (4
      cases), plaster-cast immobilization in supination (2 cases). There was no
      peculiar treatment in 3 cases. The results were influenced by operative delays.
      However we obtained 4 excellent results, 3 good results and 2 fair results.

PMID- 8289634
TI  - [Cholelithiasis in homozygous sickle cell anemia. Review of the literature].
AB  - Cholelithiasis in homozygous sickle cell disease is a common complication. Mean
      prevalence rate recorded is 27.4% with a greater frequency in the second part of
      life. It is a peculiar lithiasis, made of pigmentary stones either purs or duals,
      caused by hypersaturation of indirect bilirubin. Systematic detection of such a
      lithiasis by echography is part of monitoring homozygous drepanocytic.

PMID- 8289635
TI  - [Prevalence of human immunodeficiency virus infection (HIV) in patients with
      microbial abscesses].
AB  - From 1987 1/1 to 1989 6/30, 80 patients with purulent abscesses underwent
      serological test. Seropositivity rate of HIV was 20% i.e. higher of a 2.4 factor
      than seropositivity rate of 8.2% found in the local population not showing any
      symptoms of AIDS.

PMID- 8289636
TI  - ["Doctors and soldiers during the expedition to Egypt" (1798-1799)].
AB  - About two centuries ago, an uncommon military campaign commanded by General
      BONAPARTE aged of 29 led the French Army to Egypt. The history did not, up till
      now, underline the role of the Military Health Service. But it was tremendous, in
      spite of its poor facilities because its strong subordination to the omnipotent
      Supply Services Through the description of the conditions of the daily life of
      soldiers, the author reviews the measures which aimed at the protection of the
      troops against the usual troubles faced at by an army in the field at the end of
      the 18th Century: thirst and hunger, long marches with heavy equipment, affective
      isolation increased by the roughness of battles, diseases among with plague that
      caused heavy casualties. So, are reviewed in this framework many problems
      peculiar to that period of time: recruitment, uniforms, food, cantonments,
      spirits of the troops, personal hygiene as well as collective one; and
      consequently the measures taken by the French Military officers attached to that
      expedition to prevent some diseases and epidemics.

PMID- 8289637
TI  - Reconstruction of congenital tibial pseudarthrosis by revascularized fibular
      transplants.
AB  - Seven patients with congenital Boyd type II pseudoarthrosis of the tibia and
      fibula were treated with a revascularized osteocutaneous fibular graft from the
      contralateral side. Follow-up ranged from 20 to 96 months (mean 67 months). All
      patients had previously undergone major surgery (mean three operations). Union
      was successful in all patients although three required further surgery. At follow
      up all patients were able to walk without external support. The results were
      classified as good in two cases and fair in five cases. The postoperative period
      was, however, often complicated by stress-fracture and nonunion. Leg length
      discrepancy and valgus deformity are still unsolved problems in some cases. It
      seems probable that a primary reconstruction at an early age will prevent many of
      these subsequent problems.

PMID- 8289638
TI  - Patency and healing of microvascular prostheses: a review of 10 years of
      experimental work in Groningen.
AB  - From 1982 onwards, in Groningen, The Netherlands, we have worked on the
      experimental evaluation and development of microvascular prostheses in rats and
      rabbits. In this review article a systematic overview of this experimental work
      is presented and the results are discussed with regard to the literature to come
      to a current state of the art on (experimental) microvascular grafting with
      prosthetic conduits.

PMID- 8289639
TI  - Neither desferrioxamine nor lipoic acid enhances the cold ischaemic tolerance of
      epigastric free flaps in rats.
AB  - This study was designed to test the ability of pre- and postischaemic
      administration of desferrioxamine (DFX), a combination of a preischaemic single
      passage perfusion with hypertonic citrate solution (HCA) and postischaemic
      administration of DFX, and pre- and postischaemic administration of lipoic acid
      (LA) to enhance the cold (0 degree C) ischaemia tolerance in epigastric free
      flaps in inbred rats. The ischaemic intervals varied between 0 and 120 hr. The
      area of flap survival 2 weeks after revascularisation as a percentage of original
      flap size was recorded as an exponent of ischaemic tolerance. None of the
      treatment regimens was able to increase flap area survival. Histologically, there
      were no major differences between the different treatment regimens.

PMID- 8289640
TI  - Non-revascularized epigastric free flap: no all-or-none survival pattern.
AB  - We have previously shown that the epigastric flap in Dark Agouty rats, measuring
      approximately 6 x 4 cm with borders related to well-defined anatomical
      structures, does not exhibit an all-or-none survival pattern. This study was
      designed to investigate the survival pattern of non-revascularized epigastric
      flaps in three other rat strains (Sprague-Dawley, Brown-Norway, and Lewis). In
      concordance with our earlier observations, but in contrast to reports by many
      other groups, in none of the used strains was an all-or-none survival pattern
      observed. Survival varying from 2 to 30% (mean, 12%) of the original flap,
      without significant differences between the strains, was found. The locations of
      survival exhibited a clear pattern, probably owing to the fat pad in the subcutis
      and revascularisation from the recipient wound edges.

PMID- 8289641
TI  - Vein graft conduits versus conventional suturing in peripheral nerve
      reconstructions.
AB  - Positive results of tubulization in peripheral nerve reconstruction have been
      established in animals by many investigators. Clinically, tubulization by means
      of a venous tubulus is accepted as a reliable technique, but histological results
      are not known and functional analysis is limited. The aim of this investigation
      was to study the histological effect of venous tubuli in peripheral nerve
      reconstruction. In 20 rabbits the saphenous nerves were transected and
      anastomosed. In ten rabbits (series 1) a venous tubulus was placed around the
      nerve suture. In another ten rabbits (series 2) a venous tubulus was sutured over
      a 3 mm nerve gap. Conventional suturing was done in ten contralateral saphenous
      nerves (series 3, controls). Epineurial stitching was performed. The healing was
      studied after 3 months and after that histological analysis was performed by
      means of monoclonal antibody staining. The results of our experiments show that
      covering a nerve anastomosis with a venous tubulus did not enhance healing in
      comparison to the conventional end-to-end anastomosis, but in contrast evoked
      extensive fibrous tissue, thereby hampering regeneration of axons.

PMID- 8289642
TI  - Axonal regeneration rate through cross-face nerve grafts.
AB  - The disfigurement of irreversible unilateral facial paralysis can be corrected by
      cross-face nerve grafting in conjunction with muscle transplantation. A total of
      33 patients underwent cross-face nerve grafting using the sural nerve prior to
      undergoing the second stage of the procedure. Before a muscle transplant can be
      successfully connected to the distal end of the cross-face nerve graft, the
      regenerating axons need to have grown from the contralateral facial nerve to the
      distal end of the nerve graft. This can be tested by the Tinel sign. A
      retrospective study was performed to determine the rate of growth of regenerating
      axons through the cross-face nerve graft. A rate of axon growth of 1.8 mm/day was
      found, and also an inverse relationship between the age of the patient and the
      regeneration rate. These results can be used as a guide in planning patients'
      treatment.

PMID- 8289643
TI  - Addressing the ideal requirements by free flap phalloplasty: some reflections on
      refinements of technique.
AB  - Ideally, in phalloplasty one should aim at 1) a one-stage procedure that can be
      predictably reproduced, 2) creation of a competent neo-urethra to allow for
      voiding while standing, 3) return of both tactile and erogenous sensibility, 4)
      enough bulk to tolerate the insertion of a prosthetic stiffener, and 5) a result
      that is aesthetically acceptable to the patient. We consider 6) minimal scarring
      or disfigurement, and 7) no functional loss in the donor area further
      requirements for any ideal procedure. Thanks to ongoing refinements,
      microsurgical free flap phalloplasty techniques lead to the best results, both
      functionally and cosmetically. These refinements are presented and discussed, as
      are our experiences applying them.

PMID- 8289644
TI  - Late salvage of a "free flap" phalloplasty: a case report.
AB  - Three weeks after radial forearm free flap phalloplasty, a 28-year-old female-to
      male transsexual presented with ischaemia of the neophallus. A salvage procedure
      was started 7 hours after onset of ischemia. Thrombectomy of the arterial pedicle
      did not result in venous return of the arterial inflow. Perfusion of the flap
      with streptokinase restored venous return. Flap perfusion was confirmed by
      intraoperative direct angiography of the neophallus. Six months after this
      salvage procedure, the flap is doing well and tactile sensibility has occurred.

PMID- 8289645
TI  - "Impossible" reversed radial forearm free flap in microsurgical reconstruction.
AB  - The reversed radial forearm free flap is described and patient histories are
      presented to illustrate its unique reconstructive versatility. The valvular
      orientation of the deep and superficial forearm veins should theoretically oppose
      the reversed flow in this flap, but the venous flow is not compromised. In
      comparison to the anterograde forearm free flap the vascular pedicle is longer
      and the donor defect generates less functional and cosmetic complications because
      it is located on the proximal forearm. In a review of the literature anatomical
      details of the venous drainage are presented. Different opinions on reverse flow
      in forearm flaps are discussed and a new theory is proposed.

PMID- 8289646
TI  - Salvage of a through-knee amputation level using a free fillet of sole flap.
AB  - A young adult male sustained a compound crural fracture with a 15 cm defect of
      tibia and fibula, and an extensive soft-tissue loss of the lower leg and knee
      joint. A free fillet of sole flap was raised on the amputated foot and
      transferred to the soft-tissue defect around the femoral condyles in order to
      prevent an above-knee amputation. Intact vascularisation and sensation of the
      flap were secured by microsurgical anastomoses of the popliteal and posterior
      tibial vessels and the sciatic and tibial nerves. The patient was rehabilitated
      rapidly with a prosthesis. At the 12-month follow-up, he demonstrated excellent
      "foot" sensibility, stable soft-tissue coverage of the stump, and an optimal
      functional result.

PMID- 8289647
TI  - Inside-out vein graft promotes improved nerve regeneration in rats.
AB  - Vein grafts have been used both experimentally and clinically to bridge gaps in
      peripheral nerves. This study describes a modification of the vein graft
      technique in which vein graft conduits are pulled inside-out before anastomosis
      with proximal and distal nerve stumps. This technique creates an autogenous vein
      conduit with the collagen-rich adventitial surface exposed to the regenerating
      axons. The inside-out technique is a fast and simple modification of the standard
      vein graft technique and produces an accelerated rate of nerve regeneration and
      significantly earlier myelination compared with the results obtained from the use
      of polyethylene nerve guides and standard vein graft conduits.

PMID- 8289648
TI  - Micro-anastomosis of 0.3-0.4 mm vessels after cold ischemia using a rat model of
      toe-to-thumb transplantation.
AB  - Anastomoses of vessels of less than 0.5 mm in diameter remain a challenge from
      the technical aspect. Clinically such anastomoses are necessary for replantation
      of the distal digit in adults and whole digits in children. Survival data for
      replantation of these parts after prolonged ischemia have not yet been reported.
      Since a rat foot has an anatomic structure similar to the human hand, we used 40
      rats as models of toe-to-thumb transplantation to study the survival rates of
      transplanted toes after various periods of cold ischemia (4 degrees C) of the
      amputated part. While a 100% success rate was achieved following immediate
      transplantation of the amputated digits (control group), the survival rates were
      87.5, 75, 75, and 62.5% after transplantation of digits cooled for 24, 48, 72,
      and 96 hours, respectively (groups 2-5). No exact ischemic time limit was
      demonstrated. The results suggest that, in this model, optimal digital
      replantation results are achievable even after a 24 hour period of cooling
      preservation.

PMID- 8289649
TI  - Free fibular transfer in a growing individual (long-term results).
AB  - We present a case report of a 4-year-old in whom the distal fibula and epiphyseal
      plate had been traumatically destroyed. A free vascularized epiphyseal transfer
      using the ipsilateral proximal fibula was performed which provided good bony
      stability at the ankle, as well as excellent long-term growth characteristics. We
      demonstrate immediate postoperative results, as well as long-term (5 years)
      follow-up.

PMID- 8289650
TI  - Circumferential choledochoplasties with autologous venous and arterial grafts.
AB  - Circumferential choledochoplasties with vascular grafts have rarely been
      attempted either experimentally or in clinical practice. In this study,
      choledochoplasties using autologous venous and arterial grafts were performed in
      rats. Sixty-four rats were randomly selected into five treatment groups: A)
      venous interpositional graft replacement of a choledochus gap without a stent; B)
      venous graft with prolene stent; C) venous graft with polyethylene stent; D)
      arterial graft; E) a control group with simple resection between ligatures in the
      choledochus. The operative mortality in treatment groups B, C, D, and E, was 0,
      and 13% in group A. At 12 weeks follow-up, all the rats in group E had died,
      whereas, 52.2% (P < .05) of the rats in group A, 30% of the rats in group B, 57%
      of the rats in group C, and 92.8% of the rats in group D survived treatment.
      Surviving animals were sacrificed at 3 months for further examination. The
      morphology and caliber of the common bile duct of these rats were normal in 25%
      of the rats in group A, 33% of the rats in group B, 25% of the rats in group C,
      and 84.6% of the rats in group D. Proximal dilations were found in the rats
      presenting with abnormal morphology. The dilations were less marked in the group
      treated by arterial choledochoplasties. Laboratory and clinical cholestatic
      parameters were within normal ranges in the presence of common bile duct
      dilations less than four times the normal duct caliber.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8289651
TI  - The effect of verbal elaborations on memory in young and older adults.
AB  - The Stein paradigm was used to examine the circumstances under which verbal
      elaborations enhance memory in young and older adults. Subjects studied target
      adjectives that were embedded in one of three sentence contexts that varied in
      elaboration of the subject-adjective relationship: (1) nonelaborated base
      sentences; (2) base sentences with semantically consistent, but arbitrary verbal,
      elaborations; and (3) base sentences with explanatory verbal elaborations that
      clarified the significance of the subject-adjective relationship. The presence of
      the elaborations was varied at encoding and retrieval, and cued recall of the
      target adjectives was tested with incidental and intentional learning procedures.
      In Experiments 1A and 1B, explanatory elaborations at encoding and retrieval
      yielded the largest memorial facilitation for both young and older adults, and
      the benefit was comparable for the incidental and intentional learning measures.
      In Experiment 2, age-related differences in recall were minimal with explanatory
      elaborations at encoding and retrieval, but larger age differences occurred in
      the nonelaborated comparison conditions. In Experiment 3, explanatory
      elaborations present at encoding but not at retrieval enhanced recall when the
      original Stein stimuli were used, but not with the present stimuli. The
      implications of these results with regard to the mnemonic efficacy of verbal
      elaborations for young and older adults are discussed.

PMID- 8289652
TI  - Detecting phonemes and letters in text: interactions between different types and
      levels of processes.
AB  - In six experiments, subjects detected phonemes or letters in text presented
      auditorily or visually. Experiments 1 and 2 provided support for the hypothesis
      that a mismatch between the phoneme and letter representations of a target leads
      to detection errors. In addition, visual word unitization processes were
      implicated. Experiments 3 and 4 provided support for the hypothesis that the
      Gestalt goodness of pattern affected detection errors when subjects searched for
      letters. Experiments 5 and 6 demonstrated that the effects of unitization on the
      detection of letters in common words were decreased by altering the familiar
      configuration of the test words. The combined results of all six experiments lead
      to the conclusion that both visual and phonetic processes influence letter
      detection, that these processes communicate through a type of cross-checking, and
      that there are at least two levels of visual (and perhaps of phonetic) processing
      involved in the letter detection task.

PMID- 8289653
TI  - Dominance and noncommutativity effects in concept conjunctions: extensional or
      intensional basis?
AB  - Dominance and noncommutativity effects are investigated in relative clause
      descriptions of five conjunctive concepts (birds and pets, sports and games,
      vehicles and machines, office equipment and writing implements, and shoes and
      sports equipment). Both asymmetry phenomena are studied at the extensional level
      (using membership ratings) and at the intensional level (using feature-importance
      ratings). A clear dominance effect was found for both the membership ratings and
      the feature-importance ratings, whereas the noncommutativity effect emerged only
      occasionally in the membership ratings and almost never in the feature-importance
      ratings. The data suggested that the dominance effect and the much weaker
      noncommutativity effect have an extensional basis.

PMID- 8289654
TI  - Metaphoric reference: when metaphors are not understood as easily as literal
      expressions.
AB  - Gibbs (1990) found that metaphoric referential descriptions take longer to read
      than literal references, in contrast to the usual result that metaphors and
      literal sentences are about equally easy to comprehend. This study was performed
      as an investigation of Gibb's finding. In Experiment 1, subjects received story
      contexts in which characters clearly shared knowledge relevant to the metaphoric
      referring term. In Experiment 2, we tried to ensure that the intended referent
      was very salient by mentioning it in the sentence just prior to the crucial
      sentence. Neither of these manipulations eliminated the large response time
      advantage for literal referring expressions. In Experiment 3, the same metaphors
      were used as sentence predicates rather than as referring expressions: the
      metaphors were no more difficult to understand than literal paraphrases. Possible
      explanations for the difficulty of metaphoric references, as opposed to
      metaphoric predicates, are discussed.

PMID- 8289655
TI  - Strategic and perceptual factors producing tilt contrast in dot localization.
AB  - Encoding spatial location in a frame of reference is often biased by both
      perceptual and strategic factors. For example, tilt contrast occurs when a line
      presented in the frame of horizontal and vertical axes appears to be repulsed
      from the nearest axis, including the diagonal axis of symmetry, due to symmetry
      perception mechanisms. Research has demonstrated, however, that people can adopt
      particular viewing strategies that eliminate this effect. In Experiment 1, a
      similar tilt contrast effect was observed when subjects reproduced from memory
      the position of a single dot in this reference frame. It was hypothesized that
      this effect resulted from a combination of strategic and perceptual factors.
      Specifically, people employ an origin strategy, coding the location of the dot
      relative to the origin of the horizontal and vertical axes, thereby establishing
      a virtual line that appears tilted away from the axes due to the same perceptual
      processes affecting physically present lines. Two additional experiments support
      this hypothesis. In Experiment 2, no clear tilt contrast effect was observed in a
      perception condition, indicating that the tilt effect for dots cannot be
      accounted for by purely perceptual processes. In Experiment 3, the tilt contrast
      effect was found to be contingent upon the use of the origin strategy as opposed
      to a different strategy. The results demonstrate the importance of a viewer's
      strategy in determining the pattern of distortion observed in spatial encoding.

PMID- 8289656
TI  - An information integration approach to phenomenal causality.
AB  - Phenomenal causality was studied by using Michotte's launch event, in which
      successive motion of two objects evokes an immediate perception that the first
      motion causes the second. Information integration theory was used to address the
      complementary issues of invariant perceptual structure and individual differences
      in phenomenal causality. Three informational cues were varied conjointly:
      temporal and spatial contiguity of the two motions, and the ratio of their
      speeds. The dependent measure was a judgment of degree of causality or
      naturalness. The results showed that individual differences were related to these
      instruction conditions; the subjects showed five distinctive response patterns.
      Two were the modal patterns elicited by the instructions, and the others fell in
      between. The averaging model gave a good account of the data, with meaningful
      parameter estimates. Individual differences were localized in cue evaluation,
      whereas their integration into a unified judgment followed an invariant averaging
      rule. The results allow some reconciliation between Michotte and his critics.

PMID- 8289657
TI  - Judging interevent relations: from cause to effect and from effect to cause.
AB  - Stimulus competition was studied in college students' correlational judgments in
      a medical decision-making setting. In accord with prior findings, subjects making
      cause-to-effect (predictive) judgments discounted a stimulus event that was
      moderately correlated with a target event when rival stimuli were more highly
      correlated with the effect. However, subjects making effect-to-cause (diagnostic)
      judgments were not at all disposed to discount a stimulus event which was
      moderately correlated with a target event when rival stimuli were more highly
      correlated with the cause. The theoretical implications of these results are
      considered in connection with associative and mentalistic models of causal
      attribution.

PMID- 8289658
TI  - Activation of number facts in bilinguals.
AB  - Two experiments examined the effect of the presentation format of numbers--digits
      versus word format in the first and in the second languages of bilinguals--on
      mental arithmetic. Speed of number-fact retrieval and the presence of
      interference produced by numbers that were either numerically close to or
      associatively related to the correct answers of stored arithmetic problems (e.g.,
      2+5 and 7x8) were compared across formats. The verification of true problems was
      increasingly slower and less accurate from the digit condition to the second
      language condition. Interference was produced by both types of incorrect answers
      in the digit and first-language conditions, whereas in the second-language
      condition, it was constrained to answers that were numerically close to correct
      answers. Together, the results suggest that the retrieval of arithmetic facts and
      the automatic spreading of activation within the network of numerical facts are
      not only language-sensitive, but format-sensitive in general.

PMID- 8289659
TI  - Implicit serial learning: questions inspired by Hebb (1961).
AB  - Implicit serial learning occurs when indirect measures such as transfer reveal
      learning of a repeating sequence even when subjects are not informed of the
      repeating sequence, are not asked to learn it, and do not become of aware of it.
      This phenomenon is reminiscent of an experiment by Hebb (1961), who studied the
      repetition of sequences in a serial recall task. Two experiments investigated the
      relation between implicit serial learning and ideas about learning forwarded by
      Hebb and others who used his method. The experiments showed that implicit serial
      learning occurs even when the repeating sequence is intermixed with randomly
      generated sequences instead of being repeated continuously, that the organization
      of the sequence into regularly or irregularly grouped subsequences determines the
      extent of learning, and that the repetition effect observed does not depend on
      subjects' ability to recognize the repetition.

PMID- 8289660
TI  - Performance factors and gender-related differences in spatial ability: another
      assessment.
AB  - To explore whether test-taking styles (performance factors) can contribute to
      explaining gender-related differences on tests of spatial ability, 15 spatial
      tests were administered to three samples of subjects. On each test, number
      correct scores and ratio scores (number of items solved divided by the number of
      items attempted) were computed. In accordance with previous research findings,
      the use of ratio scores significantly reduced the magnitude of the gender-related
      differences on the Mental Rotations Test. For most of the remaining tests,
      however, the reduction of the gender-related score difference was small. It was
      concluded that the difference reduction for the Mental Rotations Test was
      specific to the format of this test. In common spatial tests, performance factors
      may account for a small portion of gender-related variance, but the bulk of this
      variance must be attributed to other factors.

PMID- 8289661
TI  - Constraining effects of examples in a creative generation task.
AB  - In three experiments we tested the conformity hypothesis--that subjects' ideas
      would conform to examples they had been shown--by using a creative generation
      paradigm in which subjects imagined and sketched new exemplars of experimenter
      defined categories. Designs made by subjects who had first seen three examples of
      ideas were compared with those of control subjects, who received no examples. In
      all three experiments, the designs of subjects who had seen the examples were
      more likely to contain features of the examples. This conformity effect did not
      significantly decrease in Experiment 2, when a 23-min task was interpolated
      between viewing the examples and generating related ideas. The hypothesis that
      the observed conformity effects may have been caused by subjects' assumptions
      that they should try to generate ideas similar to the examples was refuted in
      Experiment 3; explicitly instructing subjects to create ideas that were very
      different from the examples did not decrease conformity to the examples, and
      instructing them to conform to the examples significantly increased conformity.
      The results show that recent experience can lead to unintentional conformity,
      constraining the generation of creative ideas.

PMID- 8289662
TI  - The effects of generation on item and order retention in immediate and delayed
      recall.
AB  - Recent research has shown that generating words from fragments, relative to
      simply reading them, inhibits processing of order information. Nairne, Riegler,
      and Serra (1991) showed that this reduction in processing of order information
      leads to deficits in recall performance. In three experiments, we generally
      replicate Nairne et al.'s results and demonstrate that the deficit in recall for
      the generated items is dependent on the easy distractor task and the relatively
      short (30-sec) retention interval they used. When a difficult distractor task was
      used, generating produced a deficit in amount of order information processed, but
      actually facilitated recall when recall was delayed 80 sec. The results are
      consistent with the hypothesis that generating words inhibits order processing,
      but they do not support the contention that the reduction in order processing is
      responsible for the deficit in recall that is sometimes observed for the
      generated items. The importance of the item-order distinction in explaining the
      generation effect, as well as the role of the item-order distinction in the long
      term-memory arena, is questioned.

PMID- 8289663
TI  - Time estimation and expectancies.
AB  - The purpose of this research was to examine the influence of different types of
      expectancies on time estimation behavior. In Experiment 1, subjects were led to
      expect that a given number of trials would occur in a music perception task. In
      Experiment 2, expectancies concerning the duration of a given waiting period were
      varied. Results of both experiments indicated that the confirmation/violation of
      expectancies exerted a significant impact on duration judgments. When subjects
      received more/fewer trials than expected or waited for a duration that was
      longer/shorter than expected, the total duration of these time spans was over-
      and underestimated, respectively. Conversely, time estimates were relatively
      accurate when subjects' expectancies were confirmed. The results of Experiment 1
      further revealed that reaction time responses within the music perception task
      were also systematically influenced by the expected amount of activity. Results
      are discussed in terms of a framework that emphasizes the role of anticipatory
      attending on time estimation behavior.

PMID- 8289664
TI  - Hypertensive effect of polyunsaturated dietary fat.
AB  - Male Sprague-Dawley rats were fed a diet high in either saturated fat (lard) or
      polyunsaturated fat (corn oil) beginning at 10 weeks of age. After 10 weeks of
      diet treatment, blood pressure (BP) was 17% higher in rats fed saturated fat and
      8% higher in rats fed polyunsaturated fat than in rats fed a low-fat control
      diet. Rats fed the lard diet became obese, and their fasting insulin levels were
      elevated (38% above control). These data demonstrate that both saturated and
      polyunsaturated dietary fats induce hypertension.

PMID- 8289665
TI  - Effect of glucagon-like peptide-1 (proglucagon 78-107amide) on hepatic glucose
      production in healthy man.
AB  - The newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1)
      (proglucagon 78-107amide), stimulates insulin secretion and inhibits glucagon
      secretion in man and may therefore be anticipated to influence hepatic glucose
      production. To study this, we infused synthetic GLP-1 sequentially at rates of 25
      and 75 pmol.kg-1.h-1 into eight healthy volunteers after an overnight fast and
      measured plasma concentrations of glucose, insulin, and glucagon and glucose
      turnover by a technique involving infusion of 3-3H-glucose. Plasma levels of GLP
      1 increased by 21.3 +/- 3.1 and 75.4 +/- 3.2 pmol/L during the infusion, changes
      that were within physiologic limits. In a control experiment only saline was
      infused. During GLP-1 infusion, plasma glucose level decreased significantly
      (from 5.3 +/- 0.1 to 4.7 +/- 0.1 and 4.3 +/- 0.1 pmol/L at the end of the two
      infusion periods). Despite this, plasma insulin level increased significantly
      (from 20.5 +/- 2.9 to a peak value of 33.5 +/- 5.2 pmol/L during the second
      period), and plasma glucagon level decreased (from 9.3 +/- 1.7 to 7.1 +/- 1.0
      pmol/L). Glucose rate of appearance (Ra) decreased significantly to 75% +/- 6% of
      the preinfusion values during GLP-1 infusion. Glucose disappearance rate (Rd) did
      not change significantly, but glucose clearance increased significantly compared
      with saline. All parameters of glucose turnover remained constant during saline
      infusion. We conclude that GLP-1 may potently control hepatic glucose production
      and glucose clearance through its effects on the pancreatic glucoregulatory
      hormones. The effect of GLP-1 on glucose production is consistent with its
      proposed use in the treatment of type II diabetes.

PMID- 8289666
TI  - 24-hour energy expenditure and substrate oxidation rates are unaffected by body
      fat distribution in obese women.
AB  - Twenty-four-hour energy expenditure (EE) and nonprotein respiratory quotient
      (RQnp) were measured by indirect calorimetry in 19 upper-body-obese (UBO) and 15
      lower-body-obese (LBO) women with similar body mass index (BMI) and body fat
      percent. The measurements were performed in a respiration chamber on a
      predetermined physical activity program and a controlled diet. No differences
      between the UBO and LBO groups were found in 24-hour, daytime, and sleeping EE
      after adjustment for differences in fat-free mass (FFM). Furthermore, no group
      effect was observed in RQnp, but a positive correlation was found between RQnp
      and age. Despite the fact that an increased free fatty acid (FFA) turnover has
      been found in UBO subjects, the present study does not support the contention
      that upper-body obesity is accompanied by an increased lipid oxidation.

PMID- 8289667
TI  - Lovastatin decreases plasma and platelet cholesterol levels and normalizes
      elevated platelet fluidity and aggregation in hypercholesterolemic patients.
AB  - The lipid composition of whole platelets and the fluidity of platelet membranes,
      as well as the sensitivity of the cell to aggregation, were studied in type IIA
      hypercholesterolemic human subjects before and after treatment with lovastatin.
      Fourteen patients with primary hypercholesterolemia having initial cholesterol
      levels of 383 +/- 52 mg/dL (mean +/- standard deviation) were studied and
      compared with 21 control subjects having cholesterol levels of 187 +/- 32 mg/dL.
      Lovastatin was administered orally at a starting dose of 40 mg daily. The dose
      was increased to 80 mg daily for eight patients who did not achieve the target
      cholesterol level of 200 mg/dL at 6 weeks. Serum cholesterol level was decreased
      by 37% following 20 weeks' administration of the drug. The fluidity of platelet
      membranes expressed in terms of the fluorescence anisotropy parameter was
      determined using the probe 1,6-diphenyl-1,3,5-hexatriene (DPH). When compared
      with platelets obtained from normocholesterolemic controls, platelets from
      hypercholesterolemic patients had a higher molar ratio of cholesterol to
      phospholipids ([C/PL] 0.86 +/- 0.15 v 0.57 +/- 0.06 for controls) and of
      phosphatidylcholine to sphingomyelin ([PC/SM] 2.64 +/- 0.87 v 2.00 +/- 0.15 for
      controls), enhanced fluidity (anisotropy parameter at 37 degrees C of 0.892 +/-
      0.066 v 0.977 +/- 0.065 for controls), and a greater tendency to aggregate
      (aggregation of 84.2% +/- 6.3% v 78.5% +/- 7.6% for controls).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8289668
TI  - Plasma arginine kinetics in adult man: response to an arginine-free diet.
AB  - To explore the response of whole-body arginine metabolism to a change in arginine
      intake, plasma arginine kinetics were investigated in eight healthy adult men who
      received an L-amino acid diet supplying an Arg-rich or Arg-free intake for 6 days
      before undergoing a tracer study on day 7. The tracer protocol lasted for 8
      hours. For the first 3 hours subjects remained in the postabsorptive (fasted)
      state, and during the following 5 hours they consumed small meals at 30-minute
      intervals. Primed continuous intravenous infusions of L-[guanidino-13C]arginine,
      L-[5,5,5-2H3]leucine, and [15N2]urea were administered to estimate plasma amino
      acid fluxes and the rate of urea production. For the fasted and fed states,
      plasma arginine fluxes (mumol.kg-1.h-1, mean +/- SD) were 69 +/- 8 and 87 +/- 12
      (P < .01), respectively, for the Arg-rich diet and 63 +/- 14 and 51 +/- 7 (P <
      .01, from Arg-rich) for the Arg-free diet. Compared with the Arg-rich results,
      fed-state plasma arginine and ornithine concentrations were decreased (P < .01)
      and citrulline concentration was increased (P < .01) during the Arg-free diet
      period. Leucine fluxes and rates of urea production did not differ between the
      diet groups. The lower fed-state arginine flux in subjects receiving the Arg-free
      compared with the Arg-rich diet appears to be entirely due to the decreased rate
      of entry of arginine from the intestine in the former group.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8289669
TI  - Hypouricemic and uricosuric actions of AA-193 in a hyperuricemic rat model.
AB  - In normal rats, consecutive administrations of AA-193 for 7 days maintained the
      dose-dependent uricosuric activity without significant changes of the plasma
      urate level. In clearance studies, AA-193 produced an increase in the fractional
      excretion of urate (FEua) namely an inhibition of the net urate reabsorption in
      the nephron, which was probably dependent on the plasma concentration of the
      agent. During in vitro studies, 1 mmol/L AA-193 had no effect on liver uricase
      activity and 0.2 mmol/L AA-193 did not inhibit xanthine dehydrogenase activity.
      Therefore, it is unlikely that AA-193 at physiologic doses has a significant
      effect on either the production or degradation of urate. To assess the
      hypouricemic effect of AA-193 derived from its uricosuric effect, we used uricase
      inhibited rats produced by oxonate feeding. In the hyperuricemic rat model,
      consecutive administrations of AA-193 for 7 days increased urate excretion and
      decreased the plasma urate level. We conclude that AA-193 has a hypouricemic
      effect caused by increases in urate excretion in hyperuricemic rats.

PMID- 8289670
TI  - Systolic blood pressure during submaximal exercise: an important correlate of
      cardiovascular disease risk factors in normotensive obese women.
AB  - Body fatness, plasma lipids, lipoproteins, indicators of glucose metabolism, and
      resting as well as submaximal treadmill exercise systolic blood pressures (BPs)
      were measured in a sample of 25 normotensive obese premenopausal women. No
      association was observed between body fatness, risk factors for cardiovascular
      disease, and resting BP. However, body fatness and plasma cholesterol, low
      density lipoprotein cholesterol (LDL-CHOL), LDL apolipoprotein B (apo B), and apo
      B concentrations, as well as the high-density lipoprotein cholesterol to
      cholesterol (HDL-CHOL/CHOL) ratio, showed significant correlations with systolic
      BP measured during submaximal exercise. In addition, fasting plasma insulin
      concentrations and the glucose and insulin areas under the oral glucose tolerance
      test (OGTT) curve were both significantly associated with systolic BP during
      submaximal exercise. Partial correlation analyses revealed that the associations
      between submaximal exercise systolic BP and plasma apo B and LDL apo B levels
      were in part independent from the level of obesity. These results indicate that
      plasma concentrations of lipoproteins and insulin are important correlates of the
      systolic BP during submaximal exercise in obese premenopausal women. Further
      analyses performed on two subgroups indicated that women with high exercise
      systolic BP values exhibited significant differences in their metabolic profile
      in comparison to women with low BP during exercise. These results suggest that
      the absolute systolic BP recorded during submaximal exercise may be useful in the
      early detection of individuals at risk for the development of cardiovascular
      disease in resting normotensive obese women.

PMID- 8289671
TI  - Octreotide: a long-acting inhibitor of endogenous hormone secretion for human
      metabolic investigations.
AB  - Octreotide is a recently available, FDA-approved, long-acting analog of
      somatostatin. The efficacy and tolerability of octreotide were evaluated in a
      series of protocols in healthy volunteers to assess its suitability for use in
      clinical investigations involving short-term inhibition of endogenous hormone
      secretion. Prolonged (270 minutes) hyperglycemic clamps were used to assess
      octreotide-mediated suppression of glucose-stimulated endogenous insulin
      secretion. Compared with a saline-control infusion, octreotide (30 ng/kg/min)
      suppressed stimulated insulin (P < .0001) and C-peptide (P < .0001)
      concentrations to basal levels. During insulin-induced hypoglycemia (plasma
      glucose < 40 mg/dL), octreotide (30 ng/kg/min) effectively suppressed the
      secretion of glucagon (P < .05) and growth hormone (P < .0005). In islet cell
      clamp studies, octreotide (30 ng/kg/min) suppressed C-peptide (P < .001),
      glucagon (P < .01), and growth hormone concentrations to below basal (fasting)
      levels in all subjects. Subsequent infusion of exogenous insulin, glucagon, and
      growth hormone resulted in predictable and stable concentrations of each hormone
      during octreotide-mediated suppression of their endogenous secretion. Consistent
      with the long half-life of octreotide (approximately 90 minutes), the
      concentrations of all three hormones remained suppressed below basal levels
      throughout a 60-minute observation period following the termination of octreotide
      infusion. In separate high-dose octreotide infusion studies, octreotide (60
      ng/kg/min) did not produce any apparent additional metabolic effects, but was
      associated with an unacceptable degree of gastrointestinal side effects.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8289672
TI  - Marked reduction of pancreatic insulin content in male ventromedial hypothalamic
      lesioned spontaneously non-insulin-dependent diabetic (Goto-Kakizaki) rats.
AB  - The effects of ventromedial hypothalamic (VMH) lesions were examined in male and
      female non-obese non-insulin-dependent diabetic (Goto-Kakizaki [GK]) rats with
      respect to glucose metabolism and pancreatic insulin content. VMH lesions
      produced hyperphagia and hyperinsulinemia in both male and female GK rats. In
      male rats, plasma glucose levels of VMH-lesioned GK rats (22.7 +/- 3.1 mmol/L)
      were significantly greater than the levels of sham-operated GK rats (10.6 +/- 1.0
      mmol/L, P < .001) at 7 weeks after the operation, although there were no
      differences in these levels between VMH-lesioned and sham-operated groups in
      Wistar rats. Plasma insulin levels in male VMH-lesioned GK rats tended to be
      lower at 7 weeks than at 1 week. VMH lesions caused a significant decrease in the
      pancreatic insulin content of male GK rats (12.0 +/- 2.3 nmol/L/g pancreas)
      compared with male sham-operated rats (15.8 +/- 1.4 nmol/L/g pancreas, P < .05) 9
      weeks postoperatively. In contrast to the results in male rats, female GK rats
      showed no differences in plasma glucose levels between VMH-lesioned and sham
      operated groups at 7 weeks. Female VMH-lesioned GK rats also showed no difference
      in plasma insulin levels between 1 week and 7 weeks. The pancreatic insulin level
      of female VMH-lesioned GK rats was unchanged from that of female sham-operated GK
      rats. The insulin content was significantly greater in the VMH-lesioned Wistar
      group than in the sham-operated Wistar group, regardless of sex.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8289673
TI  - Determination of the glycogen synthesis pathway by 13C nuclear magnetic resonance
      analysis.
AB  - The level of hepatic glycogen synthesized directly from glucose was measured in
      rats with [1-13C]glucose. The nuclear magnetic resonance (NMR) spectrum of
      glucose was used to measure the distribution of the 13C label from C1 to the
      other carbons. Female Sprague-Dawley rats were surgically implanted with
      catheters in the left carotid artery and the right jugular vein, followed by a 3
      day recovery period and a 24-hour fast to deplete liver glycogen. A 2-hour
      infusion of the fasted animal with [1-13C]glucose was immediately followed by the
      removal of blood and liver tissue. The liver was divided into the right, left,
      caudate, and medial lobes, and then freeze-clamped in liquid nitrogen and stored
      at -80 degrees C. The 13C NMR glucose spectra were obtained from glycogen that
      was isolated from each liver lobe and hydrolyzed to glucose with
      amyloglucosidase. Spectra were obtained at 50.3 MHz in a narrow-bore Gemini 200
      MHz NMR spectrometer (Varian, Palo Alto, CA). The distribution of 13C onto
      glucose carbons was measured from these spectra, and the percent direct pathway
      was calculated to be 29% +/- 2.5%. Metabolic variation for the synthesis of
      glycogen within the liver was determined by measuring the direct pathway
      contribution in each of the four liver lobes. Percent direct pathway values were
      similar (P > .05) in right (35% +/- 4.9%), left (26% +/- 5.1%), medial (25% +/-
      4.9%), and caudate (27% +/- 5.6%) lobes. For some of the animals, the direct
      pathway was determined by infusion with [6-13C]glucose.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8289674
TI  - Involvement of Ca(2+)-calmodulin in platelet-derived growth factor-, fibroblast
      growth factor-, and insulin-induced ornithine decarboxylase in NIH-3T3 cells.
AB  - Ornithine decarboxylase (ODC) was induced by platelet-derived growth factor
      (PDGF), fibroblast growth factor (FGF), and insulin at doses ranging from 0.125
      to 0.5 U/mL, 25 to 500 ng/mL, and 10(-8) to 10(-7) mol/L, respectively, in NIH
      3T3 cells. The induction of ODC reached a plateau approximately 4 to 6 hours
      after addition of each mitogen. PDGF exerted a synergistic action with 10(-7)
      mol/L insulin until the concentration of PDGF reached 0.5 U/mL and exerted an
      additive action at concentrations greater than 0.5 U/mL. FGF also accelerated ODC
      induction by insulin (10(-7) mol/L) synergistically when it was added at doses up
      to 500 ng/mL. PDGF added to the intact monolayer cells caused a spike-and-plateau
      increase in cytosolic Ca2+ concentration ([Ca2+]i); the spike was independent of
      extracellular Ca2+, whereas the plateau formation was dependent on extracellular
      Ca2+. On the other hand, FGF caused a plateau-like increase in [Ca2+]i,
      exclusively dependent on extracellular Ca2+. Insulin did not affect [Ca2+]i in
      NIH-3T3 cells. Trifluoperazine (15 to 30 mumol/L) inhibited the induction of ODC
      by PDGF and FGF, but did not inhibit the effect of insulin to induce ODC. N-(6
      aminohexyl)-5-chloro-1-Naphthalenesulfonamide ([W-7] 30 to 40 mumol/L) showed a
      more profound suppressive effect on ODC induced by PDGF and FGF than N-(6
      aminohexyl)-naphthalenesulfonamide (W-5) did. There was no difference between the
      effects of W-7 and W-5 on ODC induction by insulin.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8289675
TI  - Effect of chylomicron remnants on apolipoprotein E synthesis in HepG2 cells.
AB  - The effect of chylomicron remnants (CM-R) on apolipoprotein (apo) E synthesis by
      HepG2 cells was studied. The accumulation rate of apo E in the medium was
      increased in cells incubated with CM-R (chylo-cells) compared with that in the
      control cells. However, the abundance of apo E mRNA was not greater in chylo
      cells than in control cells. The time course of apo E accumulation in the medium
      showed that apo E increased in the chylo-cells linearly up to 24 hours, whereas
      it increased in the control cells linearly only up to 6 hours, when it reached a
      plateau. The results suggest that the secretion rate of apo E was not affected by
      incubation with CM-R, but that uptake of the newly secreted apo E by the cells
      may be depressed by incubation with CM-R. Autoradiography of newly synthesized
      apo E showed that chylo-cells produced much more "larger" apo E than did the
      control cells. Two-dimensional electrophoresis of the apo E newly synthesized by
      the chylo-cells showed that the larger apo E was slightly acidic even after
      treatment with neuraminidase. Pulse-chase labeling of apo E showed that the
      larger apo E was secreted by both control and chylo-cells equally and that the
      larger apo E was converted to regular apo E in the medium more effectively in
      control cells than in chylo-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289676
TI  - Differential effects of dietary fats on sympathetic nervous system activity in
      the rat.
AB  - Fat feeding stimulates sympathetic nervous system (SNS) activity in rats. To
      determine if fats vary in their potency as stimulants of the SNS,
      [3H]norepinephrine ([3H]NE) turnover was measured in heart and interscapular
      brown adipose tissue (IBAT) of animals fed lab chow diets supplemented with
      safflower oil, coconut oil, or medium-chain triglycerides (MCT). At 5 days, all
      three fats accelerated [3H]NE turnover in heart and did so equally, but only when
      the fat supplement represented an increase in energy intake. However, after 14
      days, safflower oil and coconut oil but not MCT increased [3H]NE turnover in
      heart compared with turnover rates obtained in animals fed isoenergetic amounts
      of chow. Furthermore, the stimulatory effect of safflower oil on [3H]NE turnover
      was statistically greater than that seen in animals fed equivalent amounts of
      coconut oil. In vivo synthesis of NE assessed by accumulation of dopamine (DA) in
      heart following inhibition of dopamine-beta-hydroxylase (D beta H) was likewise
      highest in safflower oil-fed rats and lowest in those fed MCT. Thus, sympathetic
      activation by dietary fat varies among different fats, suggesting a role for
      fatty acid intake in dietary regulation of the SNS.

PMID- 8289677
TI  - Myocardial glucose transporters and glycolytic metabolism during ischemia in
      hyperglycemic diabetic swine.
AB  - We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional
      myocardial glycolytic metabolism during ischemia in anesthetized open-chest
      domestic swine. Diabetic animals were hyperglycemic (12.0 +/- 2.1 v 6.6 +/- .5
      mmol/L), and had lower fasting insulin levels (27 +/- 8 v 79 +/- 19 pmol/L).
      Myocardial glycolytic metabolism was studied with coronary flow controlled by an
      extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD)
      flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was
      constant. Myocardial glucose uptake and extraction were measured with D-[6-3H]-2
      deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The
      rate of glucose conversion to lactate and lactate uptake and output were assessed
      with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary
      perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in
      subendocardial blood flow during ischemia (from 1.21 +/- .10 to 0.43 +/- .08 mL.g
      1.min-1 in the nondiabetic group, and from 1.30 +/- .15 to 0.55 +/- .11 in the
      diabetic group). Diabetes had no significant effect on myocardial glucose uptake
      or glucose conversion to lactate under either well-perfused or ischemic
      conditions. Forty-five minutes of ischemia resulted in significant glycogen
      depletion in the subendocardium in both nondiabetic and diabetic animals, with no
      differences between the two groups. Glycolytic metabolism is not impaired in
      hyperglycemic diabetic swine after 1 month of the disease when compared with that
      in normoglycemic nondiabetic animals. The myocardial content of the insulin
      regulatable glucose transporter (GLUT 4) was measured in left ventricular
      biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289678
TI  - The effect of systemic hyperinsulinemia with concomitant amino acid infusion on
      skeletal muscle protein turnover in the human forearm.
AB  - In vitro, insulin has been shown to increase skeletal muscle (SM) protein
      synthesis and decrease SM protein breakdown. Whether these same effects are found
      in vivo in man is less clear. The study of the effect of hyperinsulinemia (INS)
      on SM protein turnover (SMPT) is complicated by hypoaminoacidemia, which can
      obviate the true effect of insulin on SMPT. To prevent this, we studied the
      effect of INS on SMPT in the human forearm with amino acid (AA) infusion to
      ensure adequate substrate for full evaluation of insulin's effect. Twelve healthy
      volunteers (aged 53 +/- 3 years) were studied. Steady-state AA kinetics were
      measured across the forearm after a systemic 2-hour primed continuous infusion of
      3H-phenylalanine (3H-Phe) and 14C-leucine (14C-Leu) in the postabsorptive (PA)
      state and in response to systemic INS (71 +/- 5 microU/mL). AAs were infused
      during INS as 10% Travasol (Travenol Laboratories, Deerfield, IL) at .011
      mL/kg/min to maintain PA branched-chain AA (BCAA) levels, known regulators of
      SMPT, and to mildly elevate total AA levels. The negative PA net balance of both
      Phe and total Leu carbons (LeuC) became positive with INS + AA infusion (Phe from
      -16 +/- 2 to 12 +/- 3 nmol/min/100 g [P < .01]; LeuC from -26 +/- 6 to 24 +/- 7
      nmol/min/100 g [P < .01]).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289679
TI  - Failure of glucagon to stimulate hepatic glycogenolysis in well-nourished
      patients with mild cirrhosis.
AB  - The ability of glucagon to stimulate hepatic glucose production (HGP) was studied
      in clinically stable cirrhotic patients (n = 8) who had, based on long-term
      follow-up evaluation, relatively good liver function (Child-Pugh A) and whose
      dietary intake and physical characteristics were comparable to those of healthy
      control subjects (n = 8). Plasma glucagon concentration was slightly but not
      significantly increased in cirrhotic patients versus control subjects in the
      basal state (190 +/- 41 v 126 +/- 24 pg/mL, P = NS) and during a continuous 180
      minute glucagon infusion at 3 ng/kg/min (349 +/- 56 v 243 +/- 37, P = NS). The
      increment in plasma glucagon level (+164 +/- 57 v +127 +/- 35, P = NS) also was
      slightly greater in the cirrhotic group. HGP (measured with [6-3H]-glucose) in
      the basal state was similar in cirrhotic and control subjects (1.79 +/- 0.09 v
      1.94 +/- 0.15 mg/kg/min, P = NS). In cirrhotic patients, stimulation of HGP by
      glucagon was blunted during the first 15 to 30 minutes of the infusion period
      (representing glucagon's predominant effect on glycogenolysis; 0.23 +/- 0.20 v
      1.06 +/- 0.19 mg/kg/min, P < .05), but it was not different from that in control
      subjects during the remaining course of the experiment (30 to 180 minutes). Basal
      plasma insulin and C-peptide concentrations did not change from baseline during
      the glucagon infusion in cirrhotics, whereas they increased slightly but not
      significantly in controls. These data demonstrate that even in the early stages
      of cirrhosis, the liver is resistant to the stimulatory effect of glucagon on
      hepatic glycogenolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289681
TI  - Plasma glucose thresholds for counterregulation after an oral glucose load.
AB  - Glucose counterregulation (GCR) plays an important role in the transition between
      exogenous and endogenous glucose delivery after an oral glucose load. This
      response is initiated when plasma glucose concentrations are decreased below
      threshold levels, previously defined in studies of insulin-induced hypoglycemia.
      In this study, we tested the plasma glucose thresholds for activation of the GCR
      response under more physiologic circumstances, ie, after glucose ingestion. We
      studied 20 normal subjects for 300 minutes after 75 g of oral glucose. Between
      150 and 300 minutes, blood samples and symptom scores were obtained at 10-minute
      intervals. After oral glucose, individual glucose nadirs were observed over a
      wide time range (160 to 290 minutes). Mean glucose concentrations decreased from
      5.3 +/- 0.2 mmol/L at 30 minutes before the nadir (-30 minutes) to 3.8 +/- 0.2
      mmol/L at the nadir (0 minutes). Mean plasma epinephrine concentrations increased
      from 210 +/- 35 pmol/L, were significantly elevated at -10 minutes (P < .05), and
      peaked at +20 minutes (1,008 +/- 184 pmol/L, P < .001). Mean plasma glucagon
      concentrations were significantly increased over baseline (100%) at +10 minutes
      (P < .001) and peaked at +30 minutes (122% +/- 7%, P < .001). Seven subjects (out
      of 15 tested) developed symptoms. Quantitative evaluation revealed a peak in the
      mean symptom score at +20 minutes, an increase from 0.4 +/- 0.3 to 2.6 +/- 0.1
      arbitrary units (P < .06).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289680
TI  - Direct effects of corticotropin on plasma lipoprotein metabolism in man--studies
      in vivo and in vitro.
AB  - To explore the roles of corticotropin and corticosteroids in the regulation of
      plasma lipoprotein concentrations, we investigated the effects of 4 days'
      administration of corticotropin 1-24 (Synacthen Depot, CIBA-Geigy, Basel,
      Switzerland) in healthy volunteers and compared them with those occurring during
      treatment with a synthetic glucocorticoid (dexamethasone). Corticotropin
      administration resulted in rapid decreases of apolipoprotein (apo) B, low-density
      lipoprotein (LDL) cholesterol, and plasma triglyceride concentrations of 20% to
      30%, whereas dexamethasone treatment did not affect any of the apo B-containing
      lipoproteins. Lipoprotein (a) [Lp(a)] level was decreased by about 30%; in this
      case, a similar reduction was noted after dexamethasone treatment. High-density
      lipoprotein (HDL) concentrations increased with both treatments; however, apo A-I
      concentrations increased only with glucocorticoid treatment, whereas HDL
      cholesterol level was elevated after both regimens. The activity of hepatic
      lipase (HL) was significantly decreased after corticotropin, but not after
      glucocorticoid treatment. LDL receptor activity, studied in cultured Hep G2
      cells, was upregulated by about 30% after incubation with corticotropin. We
      conclude that corticotropin exerts direct effects on lipoprotein metabolism in
      man, primarily on apo B-containing lipoproteins, which decrease probably due to a
      corticotropin-mediated upregulation of LDL receptor activity. The metabolism of
      Lp (a) seems to be primarily influenced by corticosteroids, which rapidly
      decrease Lp (a) concentrations. An inhibitory effect of corticotropin on HL
      activity seems to contribute, besides glucocorticoid effects on apo A-I
      metabolism, to the increase in HDL level.

PMID- 8289682
TI  - Characterization of a phenol oxidase from Cryptococcus neoformans var.
      neoformans.
AB  - In Cryptococcus neoformans, enzymic oxidation of various catechols leads to
      melanin, a proposed virulence factor. A phenol oxidase enzyme of Cryptococcus
      neoformans var. neoformans produced at 25 C has been purified from an
      ultracentrifugal supernatant of an extract of broken cells. Hydrophobic
      interaction chromatography followed by anion-exchange column chromatography
      allowed purification of the phenol oxidase. The molecular weight of the enzyme
      estimated by gel filtration was about 80,000 and a dimeric species (Mw = 160,000)
      was suggested. The isoelectric point of the protein was approximately 4.1. An NH2
      terminal 31 amino acid sequence was determined using phenol oxidase
      electroblotted onto a PVDF membrane after nondenaturing gel electrophoresis. Upon
      searching the Peptide Institute (Osaka) data base, no proteins with high degrees
      of homology were found.

PMID- 8289683
TI  - Binding of streptavidin to bacteria or fungi and its applications in detecting
      these microbes.
AB  - We have investigated the characteristics and utilities of streptavidin-binding to
      gram-negative and gram-positive bacteria and Candida spp. The pre-treatment of
      these microbes with chemical reagents such as CHCl3, NaOH, and Tween 20 have
      allowed colorimetric visualization under light microscopy or quantitation on
      nitrocellulose membranes, using streptavidin/biotinylated alkaline phosphatase
      conjugates. Analysis of this binding was confirmed by western blot. These binding
      reactions were due to the specific interaction of streptavidin with biotinylated
      proteins present in the microbes. Competition assays with free biotin or
      inhibition by an antibiotin antibody confirmed binding to these proteins. With
      knowledge of these strongly specific interactions, we attempted to reveal the
      biotinylated proteins within these microbes using clinical specimens. Using
      phagocyte-smears from blood, urine, and ascites, these intracellular microbes
      were easily detected by light microscopy. One of the septic blood samples stained
      by our technique revealed semi-digested microbial signals despite the absence of
      a signal with routine staining. This detection system, which combines
      streptavidin as a probe and biotinylated proteins as a microbial marker, is
      useful in staining for intracellular bacteria or fungi (e.g., microbial
      infections in phagocyte-smears).

PMID- 8289684
TI  - An assay method for herpes simplex virus type 1 seroprevalence survey--detection
      of antibody in saliva by avidin-biotin complex enzyme-linked immunosorbent assay
      (ABC-ELISA).
AB  - To determine whether the avidin-biotin complex enzyme-linked immunosorbent assay
      (ABC-E) is a potentially useful method for detection of herpes simplex virus type
      1 (HSV-1) antibody in saliva, paired serum and saliva samples from 129 healthy
      individuals aged 18 to 25 years were collected simultaneously and subjected to a
      neutralization test (NT) for neutralizing antibody and also to an indirect ELISA
      (IE) and ABC-E for HSV-1 specific IgG detection. Compared with the results of NT,
      the sensitivities of the IE and ABC-E for serum were both 100% (45/45), and for
      saliva 82.2% (37/45) and 93.3% (42/45), respectively. The specificity of all
      these methods was 100% (84/84). With the same ABC-E method, a significant
      correlation (r = 0.66, P < 0.001) between the OD-difference (d-OD) values of
      positive serum and saliva samples was observed. Furthermore, the consistency of
      ABC-E for salivary antibody detection was confirmed with the paired serum and
      saliva samples which were collected from four individuals followed up for eight
      months. It was clear that the ABC-E method for saliva can be used in place of the
      NT and ABC-E method for serum for seroprevalence studying of HSV-1 infection.

PMID- 8289685
TI  - Lymphocytic proliferative response to outer-membrane proteins isolated from
      Salmonella.
AB  - Porins isolated from Salmonella typhi have been demonstrated to protect against
      the challenge with this bacteria in mice. The mechanism has not been clarified,
      but could be associated with activation of both humoral and cellular immunity. In
      order to evaluate the induction of specific T cell responses, the lymphocytic
      proliferation to porins isolated from Salmonella typhimurium, Salmonella typhi
      and Escherichia coli was examined by 3H-thymidine incorporation assay in mice
      immunized with three different antigens: acetone-killed S. typhimurium, its
      porins, or outer-membrane proteins (OMPs) isolated from S. typhi. Higher
      proliferative responses were observed in mice immunized with porins and OMPs
      compared with those which received the acetone-killed bacteria. Although cross
      reactivity was observed between porins, they were not mitogenic. Moreover, porins
      were able to activate T lymphocytes isolated from mice immunized with S. typhi
      OMPs. These results suggest that T cell activation, through the release of
      lymphokines, may play a role in the induction of protective immunity with porins.

PMID- 8289686
TI  - Augmentation and suppression of TNF release from macrophages by inflammatory
      polymorphonuclear leukocytes.
AB  - It is known that polymorphonuclear leukocytes (PMNs) emerge first in local
      inflammatory sites, and then they are followed and scavenged by macrophages. We
      focused on the effect of PMN on tumor necrosis factor (TNF) release activity of
      macrophages, which is viewed as a possible indicator of the status of macrophage
      activation. One day after macrophages were cultured with fresh, intact murine
      PMNs which were induced with sodium casein, the release of TNF triggered by
      lipopolysaccharide (LPS) was augmented by low concentrations of PMNs, but
      suppressed by their high concentrations. When the PMN samples were fractionated
      into soluble and insoluble fractions, the augmenting and suppressing activity was
      partitioned; the relatively high concentrations of soluble fraction showed the
      suppressive effect whereas the insoluble fraction in lower concentrations showed
      augmentation. The suppressive activity was stable at 100 C, but the filtrates of
      the soluble fraction with membranes having cut-offs of 5,000 or 10,000 were not
      suppressive at all, suggesting the suppression is not due to low molecular
      compounds. It was also suggested that the suppressive effect for TNF release was
      not due to contaminating LPS or transforming growth factor-beta. Inflammatory
      processes may thus be positively and negatively controlled by a quantitative
      factor of initial PMN populations by regulating the TNF release activity of the
      subsequent macrophages.

PMID- 8289687
TI  - Purification of Bacillus subtilis spore coat protein by electrophoretic elution
      procedure and determination of NH2-terminal amino acid sequences.
AB  - Spore coat protein of Bacillus subtilis was purified by electrophoretic elution
      procedure. Solubilized coat protein components were separated on SDS-PAGE and the
      desired protein was recovered from the gel pieces under the optimal condition
      examined. Two purified polypeptides with molecular weights of about 40 kDa were
      obtained; each of them was in very closed size on SDS-PAGE, both retaining
      antigenic activity against anti-spore coat protein serum on immunoblot analysis.
      The N-terminal 23 and 30 amino acid sequences of them were determined, and they
      were not identical to each other and also not homologous in the sequences of coat
      proteins previously reported.

PMID- 8289688
TI  - A quantitative microanalysis of bacterial endotoxin using [3H]-labeled L-glycero
      D-mannoheptitol as a marker.
AB  - Quantitative microanalysis of bacterial endotoxin was performed using [3H]
      labeled L-glycero-D-mannoheptitol (LD-Heptitol) as a marker. Several different
      amounts of authentic L-glycero-D-mannoheptose (LD-Heptose) were reduced with 20
      micrograms of cold NaBH4 containing 2 micrograms of NaB3H4 (40 Ci/mmol) in 20
      microliters of 1 mM NaOH at 4 C for 48 hr. The product, [1-3H]-labeled LD
      Heptitol, has high specific activity, and was purified by HPLC and detected using
      a liquid-scintillation counter. As little as 50 pg of LD-Heptose was detectable,
      and the radioactivity increased dose-dependently in the 100 pg to 80 ng range
      tested. More than 2 ng of Salmonella abortus equi endotoxin could be accurately
      determined by this method. It is possible to detect 50 pg of endotoxin by this
      method, if 100% hot material (NaB3H4) is used for [3H]-labeling.

PMID- 8289689
TI  - Two distinct clusterings of the VP8* gene of rotaviruses possessing the AU-1 gene
      4 allele.
AB  - A phylogenetic tree constructed by the unweighted pair group method with
      arithmetic means (UPGMA) for the VP8* gene from 13 human and two feline rotavirus
      strains possessing the AU-1 gene 4 allele revealed that these strains could be
      classified into two clusters which did not correspond with the year of isolation
      or the host species from which they originated. Nine of 10 human strains and one
      feline strain isolated in Japan formed one cluster, whereas three human strains
      from Italy and one feline strain from Australia formed the other. Human strain K8
      from Japan was distantly related to the Australo-European clustering.

PMID- 8289690
TI  - The origin of HIV-1, the AIDS virus.
AB  - This article proposes a series of experiments to determine if cows and sheep
      could be used as animal models for HIV-1, the AIDS virus. To justify this effort,
      a substantial case is presented that HIV-1 is a natural recombinant of Bovine
      Leukemia Virus (BLV) and Visna Virus. This natural recombinant may have been
      inadvertently transferred to humans through the Intensified Smallpox Eradication
      Program conducted in sub-Saharan Africa in the late 1960s and most of the 1970s.

PMID- 8289692
TI  - A new approach to the etiopathogenesis of AIDS.
AB  - This hypothesis proposes as an explanation for the origin of the Acquired Immuno
      Deficiency Syndrome (AIDS), the homosexual transmission of spermatozoons. The
      male gamete may possess a depressing action on the immuno-competence of the egg
      aimed to prevent the rejection of the spermatozoon material. The female organism
      may be able to inactivate this action, an ability that might be absent in the
      male organism. As a consequence of the loss of its immunological competence, the
      body is invaded by a variety of microorganisms, among which certain elemental
      classes of viruses would strive successfully for long periods of time. Their
      permanence in the depressed organism would enable them to overcome the immune
      barriers present in normal subjects, becoming thus, transmissible and in some
      cases even pathogenic for the new host.

PMID- 8289691
TI  - Omega-3 fatty acids as coadjuvant treatment in AIDS.
AB  - Human immunodeficiency virus (HIV), is able to replicate in many human cells such
      as helper lymphocytes, monocytes/macrophages and glial cells.
      Monocytes/macrophages must be considered an important reservoir of HIV in vivo
      and a producer of cytokines such as Interleukin-1 (IL1) and tumor necrosis factor
      (TNF). These substances lead to an autocrine feedback loop that produces an
      increased virus replication and a secondary induction of other cytokines such as
      Interleukin 6 (IL6) and granulocyte-macrophage colony stimulating factor (GM
      CSF). These cytokines all together may be responsible for many clinical aspects
      of the disease such as headache, fever, anorexia, subtle cognitive changes, motor
      disfunctions and cachexia. The future strategies in the treatment of AIDS must be
      a combination of drugs acting on different points of viral replication and with
      synergistic potential. Omega 3 polyunsaturated fatty acids (omega-3) can be
      considered a candidate for their pleiotropic effects on immunological and
      metabolic systems. In particular, their use is considered for their ability to
      decrease IL1 and TNF production by monocytes/macrophages, as demonstrated by many
      authors. The decreased induction of these cytokines and consequently of IL6 and
      acute phase proteins may have beneficial effects on many clinical manifestations
      of AIDS such as cachexia.

PMID- 8289693
TI  - Insulin resistance in Mexican Americans--a precursor to obesity and diabetes?
AB  - Mexican Americans appear to have a strong genetic predisposition to insulin
      resistance, android obesity, and type II diabetes, apparently as a function of
      Native American genetic heritage. Theoretical considerations suggest that insulin
      resistance may be a primary factor that plays a causative role in the induction
      of both obesity and diabetes. Measures which promote optimal insulin sensitivity-
      chromium picolinate, brewer's yeast, soluble fiber supplements, metformin, very
      low-fat diet, exercise training--may have value for preventing, treating, or
      retarding the onset of obesity and diabetes, and merit clinical evaluation in
      this regard. Correction of insulin resistance may also lessen cardiovascular
      risk, in part by reducing LDL cholesterol and improving risk factors associated
      with Syndrome X. These comments are likely to be valid for other Native American
      groups at high risk for diabetes.

PMID- 8289694
TI  - Homologous physiological effects of phenformin and chromium picolinate.
AB  - The insulin-sensitizing drug phenformin, in addition to its clinical utility in
      type II diabetes, has been reported to lower blood lipids, reduce body fat,
      enhance cellular immunity, and--in rodents--to increase mean lifespan and retard
      the development of growth of cancer. Initial studies with the insulin-sensitizing
      nutrient chromium picolinate indicate that it aids glucose tolerance in type II
      diabetes, lowers elevated LDL cholesterol, reduces body fat while increasing lean
      mass, and--in rats--increases median lifespan. These effects are thus analogous
      to those reported for phenformin; chromium picolinate should be tested to
      determine whether it likewise has a favorable impact on cellular immunity and
      cancer risk. The ability of both phenformin and chromium picolinate to increase
      lifespan suggests that age-related insulin resistance may play a profound role in
      the aging process. It may not be coincidental that caloric restriction--the best
      documented technique for increasing lifespan--markedly increases insulin
      sensitivity. Safe, appropriate measures for promoting lifelong insulin
      sensitivity include a low-fat diet, exercise training, and supplemental chromium
      picolinate.

PMID- 8289695
TI  - Huntington's disease and low tryptophan diet.
AB  - Beal et al have postulated that abnormal metabolism of tryptophan or quinolinic
      acid underlies the mechanism which causes brain damage in Huntington's disease. A
      case history is reported where a low tryptophan diet was associated with an
      unexpectedly good outcome. It is possible that a low tryptophan diet may alter
      the course of Huntington's disease, either by postponing onset or diminishing the
      severity of symptoms.

PMID- 8289696
TI  - Dietary control of psychosis.
AB  - It is suggested that a dietary modification may reduce the production of dopamine
      and norepinephrine. This intervention may usefully complement the current
      treatment of psychosis.

PMID- 8289697
TI  - Manodepressive disorders: a theory based on a neurophysiological model.
AB  - In a previously presented model, a column in the cerebral cortex has activity at
      two separate levels. A few columns are under normal conditions at the high level
      of activity at a time while the rest are kept at the low level. The effects of
      changes in the number of columns that are at the high level of activity
      simultaneously have been dealt with in previous papers. It has been concluded
      that a somewhat increased number results in positive schizophrenic symptoms, and
      that too few can give negative schizophrenic symptoms. In the present paper, the
      effects of changes in a second parameter are discussed. This parameter is the
      length of time during which a cerebral column is at the high level of activity.
      It is explained how too short duration causes the manic phase in manodepressive
      disorders, and too long duration the depressive phase.

PMID- 8289698
TI  - The synaptic organization of the neocortex in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by a progressive deterioration of
      cognitive functions. Recent studies have shown that, in addition to the
      classically described lesions (plaques and tangles) found in AD, this
      neurodegenerative disorder is characterized by neuronal and synaptic loss and by
      synapto-axonal pathology. Stepwise regression analysis has shown that the major
      correlate of cognitive deficiency is the synapse loss in the prefrontal cortex,
      contributing about 70% of the strength of the correlation with global
      psychometric tests. We review evidence that supports the theory that most of the
      synaptic loss in the neocortex is derived from loss of cortico-cortical
      associational input into the modules. This hypothesis also predicts that neuritic
      plaque formation in the neocortical modules could represent an aberrant sprouting
      reaction of associational fibers responding to abnormal growth stimuli or to
      local damage. On these bases, it is also proposed that the cellular substrate of
      AD pathology is synapto-axonal, while in certain other forms of dementia such as
      Creutzfeldt-Jacob disease (CJD) and HIV encephalitis (HIVE) it is primarily
      dendritic.

PMID- 8289699
TI  - Is aluminium an etiologic contributor to alcoholic amnesia and dementia?
AB  - Neurotoxicity from excess brain exposure to aluminium (Al) is well-documented,
      from both clinical observations and animal experiments, to impair learning,
      memory and cognition. The etiology of the cognitive impairment in chronic abusers
      of ethanol--alcoholic amnesia or dementia--is not known, but it is likely to be
      multifactorial. We hypothesize that a slowly-progressive accumulation of Al in
      the brain, so as to reach functionally-toxic levels, may be one such factor. This
      could occur because of an increased permeability of intestinal mucosa to entry of
      Al, arising from sustained exposure of the gastrointestinal tract to alcoholic
      beverages, plus a trend for more frequent ingestion of antacids based on Al salts
      for treating gastritis or ulcers caused by such exposure. If this be true, use of
      Al-containing medications, as well as all avoidable exposures to Al, should be
      contra-indicated for chronic heavy drinkers.

PMID- 8289700
TI  - Does hypoxemia prevent brain damage in birth asphyxia?
AB  - The clinical syndrome of hypoxic ischemic encephalopathy (HIE) which occurs in
      association with birth asphyxia, is thought to represent a reperfusion injury
      consequent upon the generation of cytotoxic oxygen derived free radicals. It has
      recently been suggested that resuscitation of asphyxiated infants with
      unrestricted oxygen may aggravate the brain damage by causing hyperoxia and
      increased free radical production. To determine whether sustained hypoxemia may
      be protective in birth asphyxiated infants, we investigated the relationship
      between HIE and persistent pulmonary hypertension of the neonate (PPHN). The
      latter condition is also related to intrauterine and intrapartum birth asphyxia
      but is associated with persistent hypoxemia in the infant. In a retrospective
      analysis of 39 asphyxiated neonates admitted to the neonatal intensive care unit,
      we found that 28 had HIE, 10 had PPHN and only 1 had both HIE and PPHN. We
      therefore suggest that the hypoxemia due to PPHN may limit the production of
      oxygen derived free radicals in asphyxiated neonates and hence protect against
      the development of HIE. These findings lend support to current research into air
      vs. oxygen resuscitation for infants with birth asphyxia.

PMID- 8289701
TI  - Silicone-reactive disorder: a new autoimmune disease caused by immunostimulation
      and superantigens.
AB  - Over 100 cases of disorders closely resembling classic autoimmune diseases have
      been reported among patients who were injected or implanted with a diverse group
      of chemicals including paraffins, vegetable oils or silicone. Most cases have
      occurred in silicone breast implant recipients, especially those who received
      their prostheses 2-10 years prior to onset of symptoms. A high proportion of
      patients exhibit classic signs and symptoms of Sjogren's syndrome or scleroderma.
      Affected patients typically experience some combination of fatigue, myalgia,
      joint pain, sicca syndrome (dry eyes and mouth), synovitis, rash, alopecia,
      muscular weakness or lymphadenopathy, and autoantibody formation. Less commonly,
      patients may have the CREST syndrome (calcinosis, Raynaud's phenomena, esophageal
      hypomotility, sclerodactyly and telangiectasias), hypertension, pulmonary
      fibrosis, or central nervous system pathology.

PMID- 8289702
TI  - Implicit memory for stimuli presented during anaesthesia: role of anaesthetic
      cocktail and memory test.
AB  - Recently, investigators have used so-called implicit memory tests to investigate
      'hearing' during general anaesthesia. Some of them were able to demonstrate
      auditory perception in anaesthetized patients, but others have failed to find any
      evidence for intraoperative stimulus registration. We argue that differences in
      anaesthetic cocktails and memory tests can explain why some researchers have
      produced positive results, supportive of information-processing under
      anaesthesia, and others have not. It appears that stimulus registration can occur
      during surgery, regardless of anaesthetic technique. However, processing of
      complex information may only be possible during nitrous oxide anaesthesia.

PMID- 8289703
TI  - Genetic imprinting in human evolution: the decisive role of maternal lineage.
AB  - The modern study of human evolution must take into account physical anthropology,
      which examines phenotypic expression, and molecular evolution, which examines
      genotypic change. Recent independent investigations have shown that the process
      of genetic imprinting, defined as parental-dependent transmission of genetic
      traits, plays a pivotal role in human evolution. We draw on data from various
      scientific disciplines to support the hypothesis that maternal lineage via
      preferential genetic contribution, plays a decisive role in this regard. This
      concept is of more than theoretical interest, in that, current human disease
      states can be better understood and studied in the context of loss of genetically
      defined evolutionary advantage.

PMID- 8289704
TI  - Na+,K(+)-ATPase: the actual androgen receptor of the prostate?
AB  - While the nucleus may play a secondary role in androgen regulation of prostatic
      functional and structural development, I propose that, in the fully developed
      gland, the pace of all metabolism, biosynthesis, secretion and reparative
      proliferation in the gland is coupled to and set by the action of androgen on the
      Na+,K(+)-ATPase of the plasma membrane. This report identifies the three
      questions which must be asked and affirmatively answered to verify this
      hypothesis: 1. Straightforward procedures for the unambiguous demonstration of
      the coupling of (Na+,K+)-ATPase activity to glycolysis, oxidative metabolism,
      protein synthesis, cell alkalinization and citrate synthesis/secretion and that
      addition of androgen in vitro boosts the rates of the enzyme and all its coupled
      processes. 2. Demonstration that the stimulatory effect of the androgen is on the
      specific catalytic activity of each (Na+,K+)-ATPase molecule, not on the number
      of these enzyme units present. 3. Provision of means to show a likely mechanism
      for this activation; viz. shift in enzyme conformation.

PMID- 8289705
TI  - Benign monoclonal T cell proliferation in HTLV-I infection.
AB  - A spectrum of carrier states in human T lymphotropic virus type-I (HTLV-I)
      infection is proposed. The suspected process of clonal selection of HTLV-I
      infected cells results in the spectrum of nonfatal states from polyclonal to
      monoclonal virus integration. This idea is based on the discovery that monoclonal
      proviral HTLV-I DNA was detected in the fresh peripheral blood lymphocytes from
      some patients with HTLV-I-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP), a nonfatal chronic neurological disorder.

PMID- 8289706
TI  - Forced unilateral nostril breathing (FUNB) effects on the autonomic nervous
      system: an unsupported claim.
AB  - Previous claims that forced unilateral nostril breathing (FUNB) has several
      specific measurable effects on the autonomic nervous system were examined. Using
      the technique suggested by Backon, 4 subjects were tested, using an ABABA design.
      The results did not demonstrate any significant changes in heart rate, pulse
      amplitude, temperature, skin conductance response, or respiration force as a
      result of FUNB.

PMID- 8289707
TI  - The role of extracellular calcium in the pathophysiology of myotonic dystrophy.
AB  - Increased intracellular calcium levels in myotonic dystrophy have been repeatedly
      reported in many studies. In our recent investigations, the entrance of
      extracellular calcium ions through voltage sensitive calcium channels (VSCCS)
      during repetitive action potentials and late after potentials (LAPs) in tetanic
      responses were found. Since there is an increased amplitude of LAPs and after
      discharges in muscle fibers of myotonic dystrophy, we suggest that this
      pathological increase in the electrical properties of the muscle could also be
      responsible for this elevated intracellular calcium level.

PMID- 8289708
TI  - Toxic quinones produced by mammalian defense cells--causative agents for
      autoimmune reactions?
AB  - Multiple sclerosis is a disease both of the CNS compartment in which a localized
      immune response occurs, and of the peripheral immune compartment. The causative
      agent is unknown, though viruses are suspected to be among the candidates. Here a
      hypothesis is proposed, that apart from viruses, also activated granulocytes of
      the host might trigger a sensitization against self, insofar as they are suited
      to modify self-proteins. The modification results from the action of endogenous o
      quinones which are generated by activated granulocytes. o-quinones are chemically
      reactive and couple to proteins producing new epitopes. Modified self-proteins
      then may sensitize the immune system or break the immune tolerance. Granulocytes
      thus not only effectively eliminate pathogens, but cause damage to tissues of the
      host, by proteinases as described in inflammation, or by endogenous o-quinones as
      proposed here for multiple sclerosis and its models.

PMID- 8289709
TI  - Possible role of endogenous ouabain-like compounds in the pathophysiology of
      bipolar illness.
AB  - A large number of studies have documented a mood-state-related decrease in blood
      cell sodium, potassium-activated adenosine triphosphatase (Na, K-ATPase) activity
      in acutely ill bipolar patients. While it has been proposed that this enzymatic
      change may be central to the pathophysiology of bipolar illness, its genesis has
      remained obscure. Recent advances in the isolation and characterization of
      endogenously produced ouabain- or digoxin-like compounds suggest a possible
      mechanism by which these mood-state-related changes can come about. We herein
      propose that the hypothalamic-pituitary-adrenal dysregulation frequently
      documented in major mood disorders may underlie a pathological increase in the
      production of endogenous ouabain-like compounds which excessively suppresses Na,
      K-ATPase activity and results in pathological mood and energy alteration.

PMID- 8289710
TI  - Is 'senescence' of diploid cells an ad hoc mechanism suppressing 'replicon' or
      not?
AB  - So-called 'limited life span' of diploid cells does not depend on their
      unresponsiveness to growth factors from the data obtained by complete protein
      free culture of tumor cells. Limited proliferation (called limited life span) of
      diploid cells is one of the 'ad-hoc' negative regulatory mechanisms in animals,
      and can not be differentiated from other inhibitory mechanisms called 'tumor
      suppression' and 'terminal differentiation'. Metabolic imbalance induced by
      proliferation-dependent time-bomb mechanisms including infidelity of DNA repair
      is suggested to explain limited proliferation of cells. After maturation,
      autonomic progression of negative regulators in cells is induced by no
      prohibition of terminal differentiation, since organisms prepare no programs to
      stop development and differentiation. It is an attractive hypothesis that a
      proliferation-dependent time-bomb has been developed to control organogenesis for
      maturation and to determine body size. It is true that limited proliferation of
      cells can not explain longevity of individuals, although the so-called longevity
      genes play roles in ageing. Teleologically, longevity of individuals has been
      developed to produce genetic heterogeneity according to the selfish gene theory.
      This inter- and intra-species genetic heterogeneity increases the probability of
      selfish gene replication in germ cell line. After maturation and reproduction of
      DNA in germ cell line, individuals as vehicles for the DNA can be discarded by
      the 'selfish' genes.

PMID- 8289711
TI  - History, current status, and trends of radiation protection standards.
AB  - Quantitative standards for protection against exposure to ionizing radiation were
      first formulated in the 1930s. Since that time, standards have been restated
      periodically in different radiation units and conceptual frameworks that reflect
      improved understanding of the biological effects of radiation interactions and
      their consequences for human health. In the 1970s the expression of protection
      standards shifted from a dose- to a risk-based approach, with dose limits
      established to yield risks to radiation workers comparable with those for workers
      in other "safe" industries. Over the years, radiation protection standards have
      exhibited a downward trend to more rigorous limits that require increased
      commitments of personnel and resources for their enforcement. There are several
      reasons for this trend, including increased recognition of the long-term health
      effects of radiation, improved protection measures that permit radiation use at
      lower levels of exposure, growing numbers of persons exposed occupationally to
      radiation, and probably a greater intolerance to involuntary risks in society,
      with radiation targeted as a highly visible source of involuntary risks in the
      form of nuclear power plants and radioactive waste sites. In the past few years,
      reports of the Radiation Effects Research Foundation, United Nations Scientific
      Committee on the Effects of Atomic Radiation, and the National Research Council
      of the U.S. National Academy of Sciences have presented increased risk estimates
      for radiation exposure as a consequence of ongoing epidemiological analyses of
      human populations exposed to ionizing radiation. These risk estimates have
      enhanced public concern about radiation exposure and set the stage for
      discussions about the desirability of further reductions in exposure standards
      for radiation workers and members of the public. Such reductions would directly
      affect the professional activities, educational responsibilities, and
      administrative burdens of most medical and health physicists. These persons
      should understand the process of deriving risk estimates from epidemiological
      data, the factors that influence the risk estimates, how risk estimates are
      integrated into radiation protection standards, and the possible impact of more
      rigorous standards on the use of radiation in medicine.

PMID- 8289712
TI  - Constraints of the multiple-scattering theory of Moliere in Monte Carlo
      simulations of the transport of charged particles.
AB  - The breakdown of Moliere's multiple-scattering theory for short pathlengths
      occurring during Monte Carlo simulations with charged particles is demonstrated.
      It has been found that in certain conditions where the theory is assumed to be
      valid, significant distortions of the angular distribution occur that make the
      sampling of the polar angle questionable in numerous steps of Monte Carlo
      simulations. The limits of the theory have been investigated, both using a large
      number of terms in the Moliere's series and using steps of Moliere's theory where
      1/B expansions are not involved. At B = 4.5 the commonly accepted 3-term series
      expansion yields differences up to +/- 6% compared with the evaluation of the
      complete Moliere angular distribution, and up to 7 terms in the series are needed
      in order to achieve agreement within +/- 2%. One percent agreement requires B =
      10. Numerical values of the full distribution are given in terms of Moliere's
      parameters B and reduced angle theta. By using the general dependence of the
      distribution results are valid for both electron and proton Monte Carlo
      simulations in any material.

PMID- 8289713
TI  - Investigation of the convolution method for polyenergetic spectra.
AB  - The distribution of absolute dose per unit fluence from polyenergetic photon
      beams impinging upon a water phantom was calculated using two convolution
      approaches that properly account for beam hardening effects. Dose deposition
      kernels calculated previously using the EGS4 Monte Carlo code are convolved with
      the primary terma to give the dose for monoenergetic photon beams of energies
      ranging from 100 kev to 50 MeV. A polyenergetic dose distribution is composed of
      separately calculated monoenergetic components, which are appropriately weighted
      with the fluence spectrum to yield the polyenergetic dose distribution.
      Alternatively, a single convolution for the polyenergetic beam is considered,
      where a composite polyenergetic kernel is convolved with the respective
      polyenergetic terma. The effects of the polyenergetic kernel variance due to beam
      hardening as well as the effect of tilting the kernels for a diverging beam
      geometry were also examined. The depth dose data produced using the two proposed
      methods were compared with measured data and Monte Carlo simulations and showed
      good agreement.

PMID- 8289714
TI  - Automatic generation of beam apertures.
AB  - In order to specify arbitrarily shaped beam apertures for three-dimensional
      radiation treatment planning, aperture contours (or outlines) are often manually
      drawn using a beam's eye view display of the target volume and nearby normal
      structures. This can be a very time consuming process, and can be impractical for
      multileaf collimation and computer-aided optimization of a large number of
      fields. A method has been developed that allows automatic generation of aperture
      shapes that outline the target volume and may spare neighboring structures
      whenever desired. Margins of user-specified sizes (positive or negative) around
      the target and normal structures are also incorporated. For a chosen beam
      orientation, a 3D surface of each anatomic structure of interest is formed and
      projected onto a plane at the beam's isocenter. The outlines of each projected
      object are detected by an edge following algorithm, and margins are added. The
      outlines of normal structures are combined with that of the target volume to
      obtain the final aperture shape. This is done by overlaying filled versions of
      the outlines in such a way that regions of the target overlapped by normal
      structures are cut away, leaving only the target volume region to be irradiated.
      The remaining target volume outline is again detected to produce an aperture
      contour. Normal structures may split the aperture into several pieces, so this
      method detects any number of disjoint aperture contours. The results of the
      algorithm are illustrated with apertures generated for nasopharynx and prostate
      tumors, including sparing of normal tissues.

PMID- 8289715
TI  - An improved method for rebinning kernels from cylindrical to Cartesian
      coordinates.
AB  - This paper describes the errors in rebinning photon dose point spread functions
      and pencil beam kernels (PBKs) from cylindrical to Cartesian coordinates. An area
      overlap method, which assumes that the fractional energy deposited per unit
      volume remains constant within cylindrical voxels, provides large deviations (up
      to 20%) in rebinned Cartesian voxels while conserving the total energy. A
      modified area overlap method is presented that allows the fractional energy
      deposited per unit volume within cylindrical voxels to vary according to an
      interpolating function. This method rebins the kernels accurately in each
      Cartesian voxel while conserving the total energy. The dose distributions were
      computed for a partially blocked beam of uniform fluence using the Cartesian
      coordinate kernel and the kernels rebinned by both methods. The kernel rebinned
      by the modified area overlap method provided errors less than 1.7%, while the
      kernel rebinned by the area overlap method gave errors up to 4.4%.

PMID- 8289716
TI  - "Zero-field" dose data for 60Co and other high-energy photon beams in water.
AB  - A procedure of separating the primary- and scatter-dose components in therapeutic
      photon beams is examined. It is based on the observation that the scatter-dose
      component is proportional to the variable z = rd/(r+d), where r and d are beam
      radius and depth in phantom, respectively. It is, therefore, possible to express
      an absorbed dose in the form of a linear equation D(r) = P+Nz, where at a fixed
      depth d, both primary dose P and coefficient N are constant. A method of linear
      extrapolation of an absorbed dose D(r) to "zero-field" size, i.e., r = 0, is
      utilized. Since Monte Carlo technique is capable of scoring separately the
      primary- and scatter-dose components, it is used to evaluate the accuracy of the
      linear extrapolation method within the range of 60Co-15-MV nominal photon
      energies. The results demonstrate that this method is sufficiently accurate to
      obtain the primary dose component in photon beams. For 60Co gamma radiation in
      water, tabulated sets of measured depth-dose data are analyzed by the linear
      extrapolation method to review "zero-field" dose values [percentage depth dose
      (PDD) and tissue-air ratio (TAR) tables of the British Journal of Radiology,
      Suppl. 17]. The "zero-field" PDD data are found to be accurate within limits of
      experimental uncertainties. Inconsistencies in the TAR table are illustrated and
      discussed. 60Co tables of relative doses, D(r,d)/P(dmax), including "zero-field"
      values for both fixed SSD and isocentric geometries, are generated. Dose
      calculation in irregular fields is considered. The linear extrapolation method is
      recommended as a standard procedure for separating primary dose from depth-dose
      data in high-energy photon beams.

PMID- 8289717
TI  - A simple one-dimensional model for understanding planar dose-versus-depth
      profiles in mixed photon/electron fields.
AB  - A one-dimensional model is described for illustrating the perturbing effects of
      mixed photon/electron fields on planar dose-versus-depth profiles in low Z
      materials (Z < or = 20), and at moderate photon energies (0.3-10 MeV). An
      electron field may arise from photon interactions in filters upstream of a dose
      versus-depth experiment. The effects of upstream mass, scattering of electrons
      out of a gap between a filter and the experiment, and differences between the
      incident electron energy distribution and locally produced KERMA are modeled and
      compared to Discrete Ordinates calculations. At transitional depths in a dose
      versus-depth experiment, the distortions can be significant and obscure the
      profile of the photon component alone.

PMID- 8289718
TI  - Newly computed f-factors for use in radiation dosimetry.

PMID- 8289719
TI  - Comments on "Sampling techniques for the evaluation of treatment plans" [Med.
      Phys. 20, 151-161 (1993)].

PMID- 8289720
TI  - Comments on "Sampling techniques for the evaluation of treatment plans" [Med.
      Phys. 20, 151-161 (1993)].
AB  - We believe that, for the purpose of evaluation and optimization of treatment
      plans, quasirandom sampling is superior to grid sampling and should be the method
      of choice. We believe it to be on average more efficient than grid sampling
      (i.e., more accurate for any given number of dose estimates) and, even more
      importantly, more reliable in that it is subject to less variability due to shape
      and orientation of the particular VOI--as demonstrated in Fig. 2. As a rule of
      thumb we recommend using about 400 quasirandom samples per volume of interest.
      For many situations this number is a conservative estimate; for a few situations
      more samples might be necessary. Optimal sampling for the purpose of calculation
      and presentation of the dose distribution is a different story which we have
      addressed elsewhere.

PMID- 8289721
TI  - Evaluation of fixed- versus variable-modulation treatment modes for charged
      particle irradiation of the gastrointestinal tract.
AB  - The clinical usefulness of variable-modulation dose delivery of neon ion and
      proton beams over fixed-modulation beams is evaluated for several patients with
      tumors in the gastrointestinal tract by comparing dose distributions, dose volume
      histograms, and predictions of normal tissue complication probabilities
      calculated with the two methods. Both techniques provide excellent coverage of
      the target volume with neon ion and proton beams. The advantage of variable
      modulation is that less dose is delivered proximal to the target volume. For
      tumors in the gastrointestinal tract, this implies that less dose is given to the
      liver, gut, kidneys, and lungs. For the ten patients considered in this study,
      variable-modulation reduced the total integral dose by an average of 17% for neon
      ion beams and by 18% for protons as compared to fixed-modulation. If the tumor
      volume is excluded, the reduction in the integral dose to normal tissues ranged
      from 15% to 32% for neon ions and from 18% to 34% for proton beams. These gains
      are larger than those anticipated on the basis of an analytic study by Goitein
      and Chen [Med. Phys. 10, 831-840 (1983)], which predicted integral dose
      reductions of the order of 10% for protons and 14% for neon ions. They are also
      larger than those reported in a similar study by Urie and Goitein [Med. Phys. 16,
      593-601 (1989)] for proton irradiation of skull-base tumors. This is probably
      because the tumors in the GI tract considered in this study were more irregularly
      shaped than Goitein and Chen's analytic model assumes. The results of this study
      also suggest that due to increased sparing of normal tissues, the number of
      different portal directions required to achieve a satisfactory treatment plan
      will be reduced for variable-modulation beam delivery systems. This implies that
      variable-modulation treatment plans will be easier to execute than current fixed
      modulation plans.

PMID- 8289722
TI  - Aperture size to therapeutic volume relation for a multielement ultrasound
      system: determination of applicator adequacy for superficial hyperthermia.
AB  - Three-dimensional acoustic and thermal models were developed to simulate
      superficial hyperthermia treatments using a new multielement planar ultrasonic
      system. Typical power density and steady-state temperature distributions are
      presented. A parametric study was performed to determine the relationship between
      therapeutic volume (volume at and above 42 degrees C) and aperture size (number
      of active elements). The parameters investigated were: maximum allowable
      temperature, skin surface temperature, blood perfusion (thermal diffusion
      length), acoustic absorption, and frequency. Results showed that this device
      produces well distributed sound beams with lateral dimensions comparable to the
      aperture size. These simulated results were in agreement with experimental
      measurements. The simulated temperature distributions were uniform at each depth
      across the applicator's aperture. The main heating characteristics found were:
      (1) the therapeutic volume was directly proportional to the aperture size; (2)
      the lateral dimensions of the therapeutic volume were independent of the
      parameters studied and remained practically constant with depth for several
      centimeters, with a very rapid increase near the skin surface and a very rapid
      fall off at depth; and (3) therapeutic penetration was strongly dependent on
      maximum allowable temperature, frequency, and acoustic absorption; and weakly
      dependent on blood perfusion and skin surface temperature. These heating
      characteristics are new in commercial systems for superficial hyperthermia.
      Despite the well-distributed beams, it was found that in order to produce
      adequate hyperthermia with this device the lateral dimensions of tumors must be
      smaller than the applicator's active aperture and that thermal depth coverage
      must be monitored during treatments. Guidelines for aperture selection and
      thermometry strategies are discussed.

PMID- 8289723
TI  - The response characteristics of a newly designed plane-parallel ionization
      chamber in high-energy photon and electron beams.
AB  - A new plane-parallel ionization chamber has been designed by Attix to overcome
      the shortcoming of previous commercially available parallel-plate ionization
      chambers for dosimetry in high-energy photon and electron beams in radiation
      oncology. This investigation details the performance characteristics of this new,
      commercially available plane-parallel chamber. The magnitude of the polarity
      effect in high-energy electron beams is shown to be less than 1% while the
      polarity effect in high-energy photon beams is lower than several other plane
      parallel ionization chambers. The over response of the chamber in the buildup
      region of normally incident high-energy photon beams is less than 1% for 6- and
      24-MV x rays while the response of the new chamber to obliquely incident x-ray
      beams was affected much less by the angle of beam incidence than the other
      chambers tested. These superior response characteristics are primarily due to the
      construction characteristics of the collecting electrode arrangement. The Attix
      chamber, with a wall diameter (w) of 40 mm and a plate separation (s) of 1 mm,
      has an aspect ratio, (w/s), of 40. This exceeds the previously reported design
      criterion of w/s > or = 25 required to properly measure surface and buildup dose
      in either conventional therapy beams or in beams that are highly contaminated.

PMID- 8289724
TI  - X-ray sources of medical linear accelerators: focal and extra-focal radiation.
AB  - A computerized tomography (CT) reconstruction technique has been used to make
      quantitative measurements of the size and shape of the focal spot in medical
      linear accelerators. Using this technique, we have measured the focal spots in a
      total of nine accelerators, including (i) two Varian Clinac 2100c's, (ii) two
      Atomic Energy of Canada Ltd. (AECL) Therac-25's, (iii) two AECL Therac 6's, (iv)
      a Siemens KD-2, (v) a Varian Clinac 600c (4 MV), and (vi) an AECL Therac-20. Some
      of these focal spots were monitored for changes over a 2-yr period. It has been
      found that (i) the size and shape of the source spot varies greatly between
      accelerators of different design ranging from 0.5 to 3.4 mm in full width at half
      maximum (FWHM); and (ii) for accelerators of the same design, the focal spots are
      very similar. In addition to the measurements of the focal spot, a new technique
      for measuring the magnitude and distribution of extra-focal radiation originating
      from the linear accelerator head (flattening filter, primary collimator) has also
      been developed. The extra-focal radiation produced by a Varian Clinac 2100c
      accelerator was measured using this technique and it was found that the extra
      focal radiation accounts for as much as 8% of the total photon fluence reaching
      the isocenter. The majority (75%) of this extra-focal radiation originates from
      within a circle 6 cm in diameter at the target plane. The source MTFs for each of
      the measured focal spots have been calculated in order to assess their influence
      on the spatial resolution of verification images. The limiting spatial resolution
      (i.e., 10% modulation) for all the source MTFs is 1.8 mm-1 or greater when used
      for transmission radiography at a magnification of 1.2. The extra-focal
      radiation, which produces a low-frequency drop in the source MTFs of up to 8%,
      changes with field size. As a result, the source MTFs of linear accelerators
      depend not only on the design of individual accelerators and image magnification,
      but also on the field size used when forming an image.

PMID- 8289725
TI  - The penumbra of a 6-MV x-ray beam as measured by thermoluminescent dosimetry and
      evaluated using an inverse square root function.
AB  - Data on the dose distribution in the penumbral region of megavoltage x rays are
      of importance for most radiotherapy planning systems. For medical linear
      accelerators the distance between the points representing 20% and 80% of the
      central axis dose (20/80) is typically only a few millimeters. To achieve good
      spatial resolution a radiation detector with small physical size has to be used
      for penumbra measurements. The penumbra in a 6-MV therapeutic x-ray beam was
      investigated for field sizes of 10 x 10 cm2 and 20 x 20 cm2 at depth of maximum
      dose (dmax = 1.5 cm) and at 10-cm depth in a solid water phantom. In addition,
      the field edge of an independent jaw driven to the center of the axis of the
      primary collimator was investigated. LiF thermoluminescent (TL) ribbons and rods
      were used embedded in solid water in different geometries resulting in relative
      detector sizes of 1, 3.1, and 6 mm. A forming function based on an inverse square
      root function was used to fit the experimental penumbra measurements. For the
      asymmetric field an amendment to the function is proposed to give a better fit
      for the experimental data. From the penumbra measured with the three different
      detector sizes, a penumbra can be extrapolated for an infinitesimal small
      detector. The extrapolated penumbral width (20/80) was found to be 2.3, 3.2, and
      2.7 mm at dmax for the 10 x 10-cm2 symmetric, 10 x 10-cm2 asymmetric, and 20 x 20
      cm2 field sizes, respectively. The 20/80 values at 10-cm depth in the solid water
      phantom for the same radiation fields were 4.2, 4.3, and 4.1 mm, respectively.

PMID- 8289726
TI  - Dosimetry of 6-MV x-ray beam penumbra.
AB  - The measurement of x-ray beam dose profiles in the penumbral region, using
      silicon diode, ionization chamber, TLD, and film dosimetry, has been investigated
      for a 6-MV beam defined by independent collimators. Penumbral width (80%-20%) at
      dmax, as measured by diode, film, and TLD was found to be 3.6, 3.6, and 3.4 mm,
      respectively. These results reflect the relative sensitive widths of each of the
      measurement systems (2.5, 2.0, and 1.0 mm, respectively). An empirical forming
      function was used to relate the penumbral shape measured with a finite-sized
      detector to that which would be measured with a point detector, the width of the
      point detector penumbra calculated from the diode penumbra is 3.4 mm, indicating
      that the TLD rods are a good approximation to a point detector. An alternative
      method of determining the width of a point detector penumbra is to extrapolate
      the penumbral widths obtained using two or more detectors of sensitive width.
      With this method, using Farmer and RK ionization chambers, a point detector
      penumbra width of 3.1 mm is obtained. An EGS4 Monte Carlo simulation, where a
      point source was assumed, gave a penumbral width of 2.8 mm. Negligible
      differences between the penumbra of beams defined by symmetric and asymmetric
      collimators was observed.

PMID- 8289727
TI  - Dosimetry of wedged fields with asymmetric collimation.
AB  - Shaping of wedged fields with asymmetric collimators (independent jaws) produces
      dosimetric effects which need to be taken into account when calculating isodose
      distributions and accelerator monitor units. These effects were studied using ion
      chamber dosimetry in a water phantom. Wedged fields of 30 degrees to 60 degrees
      wedge angles were shaped by an asymmetric collimator. A system of dose
      calculation was developed to take into account the changes in dose in the open
      portion of the field. The formalism utilizes regular symmetric field parameters
      (e.g., Sc, Sp, and TPR). Calculated point doses and profiles agreed well with the
      measured data.

PMID- 8289728
TI  - Energy response of agar-alanine free radical dosimetry to therapeutic electron
      beams.
AB  - Calculations of the energy response of an agar-alanine phantom dosimeter (AAPD)
      to electrons in the energy range of 0.15-20 MeV together with experimental
      results at 16 MeV are presented. It is shown that the sensitivity of the EPR
      dosimeter (EPR signal/Gray) is independent of alanine crystal size and varies
      less than 2%, in the electron energy range indicated. Thus, the measured free
      radical density distribution may be used directly as an indication of the
      absorbed dose distribution in an irradiated phantom.

PMID- 8289729
TI  - A versatile method for planning stereotactic brain implants.
AB  - Our approach to planning stereotactic 125I brachytherapy of brain tumors has
      involved least-squares optimization of individual seed positions within the
      target contour, followed by repeated combining of seeds from nearest-neighbor
      catheters in order to achieve an acceptably low number of catheters and an
      acceptable-separation of entry points. In one option, the catheters diverge from
      an extra-cranial point that can be close to the skull if all catheters are to be
      placed through a small craniectomy to treat a larger-diameter target. In another
      option, catheters converge toward a point beyond the target, to facilitate
      perpendicularity at the skull surface if a separate opening is to be drilled for
      each catheter. In either case, the fact that seed orientations are known, permits
      including anisotropy in dose calculations. Trial seed locations are constrained
      to a target region defined on a 1-mm mesh, both in the initial optimization of
      single-seed catheters and in subsequent combinations followed by tune-up
      optimizations. In the optimization process, sum-of-squares contributions are
      weighted more heavily when the dose rate is lower than the target dose rate; the
      weighting imbalance falls short of keeping all target points above the target
      dose rate and requires targeting on a dose rate about 25% higher than the desired
      minimum dose rate.

PMID- 8289730
TI  - Anisotropy functions for 103Pd, 125I, and 192Ir interstitial brachytherapy
      sources.
AB  - Anisotropy of dose distributions around 103Pd, 125I, and 192Ir sources for
      interstitial brachytherapy was examined. Dose rates around 125I models 6702 and
      6711 and 192Ir sources were measured using lithium fluoride thermoluminescence
      dosimeters (LiF TLDs) in a water-equivalent, solid phantom. From these measured
      data for 125I and 192Ir and the previously published measured data for 103Pd,
      isodose rate contours were determined using a bivariate interpolation and smooth
      surface fitting algorithm. The anisotropy functions, F(r,theta), as defined by
      the Interstitial Collaborative Working Group (ICWG) for each source, were
      determined. Also, 4 pi-averaged anisotropy factors, phi an(r), for use in point
      source approximation, have been calculated at radial distances varying from 1-10
      cm for 103Pd, 125I, and 192Ir sources. The anisotropy factors had average values
      of 0.90, 0.93, 0.95, and 0.98 for 103Pd, 125I model 6711, 125I model 6702, and
      192Ir, respectively. The anisotropy factors determined from dose measurements in
      phantom are observed to be closer to unity than from those determined previously
      from in-air measurements. This can be attributed to the smoothing of two
      dimensional dose distributions due to the presence of more scattered photons in
      the phantom measurements compared to in-air measurements. Because in-phantom
      measurements simulate more closely the brachytherapy patient, data from these
      experiments are recommended for a more accurate determination of dose
      distributions around clinical brachytherapy implants. In this work, we present a
      complete set of source data for two-dimensional dosimetry following the ICWG
      formalism.

PMID- 8289731
TI  - Dosimetric characteristics of a double wall 125I source for interstitial
      brachytherapy.
AB  - Recently, a newly designed encapsulated source of 125I has become commercially
      available for use in permanent and temporary interstitial brachytherapy. The 125I
      sources in current use come in two different configurations: the Model 6711
      source (Medi Physics/Amersham) for permanent implants has radioactive iodine
      adsorbed on the surface of a silver wire, and the Model 6702 (Medi
      Physics/Amersham) source for temporary implants has radioactive iodine absorbed
      in three spherical resin balls. Both of these iodine sources are encapsulated in
      a thin-walled shell (0.05-mm thick) made of titanium. The newly designed 125I
      source (Best Industries Model 2300 series) contains radioactive iodine adsorbed
      on a tungsten wire that is encapsulated by two walls of titanium. This double
      walled 125I source offers the following potential advantages: (i) Because it
      contains radioactive iodine on the ends as well as the circular surface of the
      tungsten wire, it can produce a more isotropic dose distribution than the sources
      in current use; (ii) because it is available in a wider range of source
      strengths, it is suitable for both temporary and permanent implantation; (iii)
      because it has a tungsten radiographic marker, source localization is
      considerably easier than the 125I Model 6702 source that has no radiographic
      marker; and (iv) because it uses a double-walled encapsulation the risk of
      radioactive contamination due to source rupture is considerably reduced. In this
      work, dose distributions produced by the new design 125I source (Model 2300) for
      interstitial brachytherapy have been measured using LiF TLD's in a Solid Water
      phantom. Dosimetric characteristics of the new 125I sources are compared with
      those of the currently available 125I sources.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289732
TI  - The influence of arc weights on the dose distribution for single target
      radiosurgery.
AB  - To stereotactically irradiate ellipsoidal inclined arteriovenous malformations
      (AVMs) with a single isocenter one can use an adjusted inclined irradiation space
      with a reduced angular range of arcs. If one uses the maximum available
      irradiation space it is necessary to weight some of the arcs in order to closely
      encompass the lesion. It has been found that there is a relationship between the
      lesion inclination angle beta and the weights of arcs. Conversely when the beta
      angle is known, the weights of the arcs can be determined in advance by means of
      weighting vectors. The dose volume analysis shows that the isodose volumes remain
      constant for the different weighting vectors except for the 10% isodose volume
      which increases slightly as the linear weighting vector's slope alpha increases.
      Moreover, this procedure permits the optimization of the superimposition between
      the lesion and the reference isodose. These results enable the construction of an
      "a priori knowledge" database that can be included in an optimization algorithm
      procedure.

PMID- 8289733
TI  - Engineering modifications for dynamic stereotactically assisted radiotherapy.
AB  - To perform dynamic stereotactic radiotherapy, a number of modifications to the
      commercial linear accelerator were required and these are described in this
      report. A couch drive system was added to rotate the couch in synchrony with the
      gantry. A high dose rate beam for this technique is acquired through a head
      modification, which allows easy removal of the radiation field flattener. Because
      of these modifications, a number of changes and additions were required to the
      linac interlock system, including a complete new chain of interlocks for use with
      the stereotactic technique.

PMID- 8289734
TI  - High-resolution x-ray imaging at soft diagnostic energies using a silicon
      photodiode array.
AB  - A linear self-scanned silicon photodiode array (PDA) has been used as a high
      resolution detector for small object computed tomography using soft diagnostic x
      rays. The imaging performance of the PDA when used to detect x rays directly has
      been characterized for x-ray spectra between 24 and 69 kVp. The modulation
      transfer function (MTF) was measured to 40 cycles/mm (twice the PDA sampling cut
      off frequency) by double sampling an edge profile using a half-detector shift.
      The MTF had no significant energy dependence, a 10% value at 28 cycles/mm, and a
      3% low-frequency drop. The detective quantum efficiency zero-frequency value
      ranged from 1.5% with an 18-keV average-energy beam to 0.4% at 40 keV, and
      decreased further with increasing spatial frequency. It was found that the
      effective thickness of the silicon detector was 22 microns. This is typical of
      the expected diffusion length of minority carriers in doped silicon. An average
      of 4.6 +/- 1 eV was required to generate one e-h pair in the PDA, consistent with
      the accepted value of 3.6 eV in silicon. No evidence of radiation damage was
      observed after an accumulated exposure of over 5000 R. Use of the PDA is
      demonstrated by generating computed tomographic images using a third-generation
      (rotate only) reconstruction algorithm. Images of a resolution test phantom, a
      pen and pencil, a mouse head, and bone biopsy specimen taken from a patient with
      osteoporosis are shown.

PMID- 8289735
TI  - Mammographic scanning equalization radiography.
AB  - It is well recognized that variations in breast thickness and parenchymal
      composition can produce a range of exposure which exceeds the latitude of high
      contrast mammographic film/screen combinations. Optimal imaging of the dense
      breast is desired since 30%-60% of women present with dense breasts, and they are
      believed to be at the highest relative risk of developing breast cancer. The
      application of scanning equalization radiography to mammography has been
      investigated through the construction and characterization of a prototype
      mammographic scanning equalization radiography (MSER) system, designed to image
      mammographic phantoms. The MSER system exposes a Min-R/MRH cassette by raster
      scanning a 2.0 x 1.6 cm beam of pulsed x-rays across the cassette. A scanning
      detector behind the cassette measures the local x-ray transmission of the breast.
      Feedback of the transmission information is used to modulate the duration of each
      x-ray pulse, to equalize the film exposure. The effective dynamic range of the
      MSER system is 25 times greater than that of conventional mammography. Artifact
      free images of mammographic phantoms show that MSER effectively overcomes the
      latitude limitations of film/screen mammography, enabling high contrast imaging
      over a wide range of object x-ray transmission. Anthropomorphic phantom images
      show that MSER offers up to a sixfold increase in film contrast in the normally
      underexposed regions of conventional mammograms. Characterization of the entrance
      exposure shows that there is not a significant difference in exposure between
      MSER and conventional mammographic techniques, suggesting that both would pose
      comparable risk to the patient. Calculations show that the construction of a
      clinical multiple beam MSER system is feasible with minor changes to existing
      technology.

PMID- 8289736
TI  - Observer performance and dose efficiency of mammographic scanning equalization
      radiography.
AB  - The detection of fibrils, microcalcifications, and low contrast lesions is vital
      to the detection of early breast cancer. It has been shown through sensitometric
      measures and anthropomorphic phantom images that mammographic scanning
      equalization radiography (MSER) overcomes the latitude limitations of
      conventional mammographic techniques. MSER increases image quality by regional
      modulation of the entrance exposure to suit the local variations in x-ray
      transmission within the patient. In order to assess the effect of equalization on
      the detection of breast lesions, we have compared observer performance in MSER
      and conventional imaging techniques. The observation tasks were the threshold
      visualization of fibrils, microcalcifications, and low contrast discs (simulating
      lesions), located on a uniform background. The performance of the observers was
      determined for a range of background x-ray transmission simulating the range of
      transmission generated by variations in breast composition and thickness. For the
      conventional images, the threshold visible diameter of the fibrils,
      microcalcifications, and low contrast discs, increased as the x-ray transmission
      of the phantom changed from that for which the film was optimally exposed. For
      the MSER images, the performance of the observers was almost independent of the
      background transmission of the object since MSER ensures that the film is
      optimally exposed for a large range of object transmission. Even with significant
      changes in object x-ray transmission, only minor changes in fibril,
      microcalcification, and disc detection were observed. Utilizing the results of
      the contrast-detail experiment, a dose efficiency comparison of conventional and
      MSER imaging techniques was performed. The dose efficiency analysis showed that
      MSER varied the incident exposure so as to maintain consistent performance of the
      observer, over the entire breast. These results suggest that MSER would improve
      the ability of radiologists to detect early breast cancer in women presenting
      with mammographically dense breasts, in a very dose efficient manner.

PMID- 8289737
TI  - Noninvasive digital energy subtraction angiography with a channeling-radiation x
      ray source.
AB  - Channeling radiation could provide a viable source for digital energy subtraction
      angiography (DESA). A signal to noise ratio (SNR) of 6.2 for a resolution of 0.5
      mm x 0.5 mm could be achieved using a 6-mA 100-ms 20-MeV electron-beam pulse and
      a diamond channeling crystal as the x-ray source. This article investigates the
      choice of a DESA contrast agent and the parameters of a channeling-radiation x
      ray source to develop a channeling-radiation DESA imaging system. The production
      of dual-energy peaks, the maximum available x-ray flux, the advantages of an area
      exposure, the necessity of a mosaic Bragg-crystal filter to reduce patient dose,
      the optimal energy separation of the peaks for a quasi-monochromatic x-ray
      source, and the reduction of the signal from bone are discussed, leading to
      estimated SNRs and image resolution for a channeling-radiation imaging system.
      The computer analysis developed to calculate the image quality is also discussed.

PMID- 8289738
TI  - Analysis of projection geometry for few-view reconstruction of sparse objects.
AB  - In this paper certain projections are examined as to why they are better than
      others when used to reconstruct sparse objects from a small number of
      projections. At the heart of this discussion is the notion of "consistency,"
      which is defined as the agreement between the object's 3-D structure and its
      appearance in each image. It is hypothesized that after two or more projections
      have been obtained, it is possible to predict how well as subsequent view will
      perform in terms of resolving ambiguities in the object reconstructed from only
      the first few views. The prediction is based on a step where views of the partial
      reconstruction are simulated and the use of consistency to estimate the
      effectiveness of a given projection is exploited. Here some freedom is presumed
      to acquire arbitrary as opposed to predetermined views of the object. The
      principles underlying this approach are outlined, and experiments are performed
      to illustrate its use in reconstructing a realistic 3-D model. Reflecting an
      interest in reconstructing cerebral vasculature from angiographic projections,
      the experiments employ simulations based on a 3-D wireframe model derived from an
      internal carotid arteriogram. It is found that for such an object, the
      predictions can be improved significantly by introducing a correction to account
      for the degree to which the object possesses some symmetry in shape. For objects
      sufficiently sparse, this correction is less important. It is concluded that when
      the number of projections is limited, it may be possible to favorably affect the
      reconstruction process in this manner.

PMID- 8289739
TI  - Computer simulation of broad-beam and narrow-beam attenuation in lead for
      diagnostic x-ray energies.
AB  - Significant differences between broad- and narrow-beam transmission measurements
      for lead protective barriers have been noted for x-ray beams in the diagnostic
      energy range. Work reported in this paper indicates that these differences in
      transmitted exposure between broad- and narrow-beam geometry measurements are
      primarily the result of two independent interaction processes; the transmission
      of K-characteristic photons produced in the barrier, and coherently scattered
      photons. The magnitude of these effects was studied for x-ray spectra between 70
      and 150 kVp. The K-characteristic component was found to be maximal at 150 kVp,
      while the coherently scattered contribution was found to be maximal for thick
      barriers and at lower energies. The effect of beam field size on relative
      transmitted intensities was also studied and found to increase with increasing
      field size up to 30 cm. A detector-to-barrier distance of 10 cm was found to
      maximize the K-characteristic component. For a typical diagnostic x-ray potential
      of 100 kVp, the K-characteristic component was found to be less than 7% of the
      total transmitted beam. Voltage wave form considerations were found to be
      significant as has been previously reported. The contribution of K-characteristic
      photons has been mathematically modeled and a computer program written to allow
      the rapid computation of broad beam transmission exposures for lead barriers,
      once the appropriate beam specifications have been entered.

PMID- 8289740
TI  - Signals, noise and the join-count statistic.

PMID- 8289741
TI  - Is CT simulation the wave of the future?

PMID- 8289742
TI  - Anesthesia for cardiac patients--1993 and beyond.

PMID- 8289743
TI  - Valvular heart disease: Anesthetic considerations in non-cardiac surgery.
AB  - In all cases of valvular heart disease one should avoid heavy premedications.
      This will ensure that the balance between preload and afterload is maintained and
      will avoid respiratory depression which may aggravate pulmonary hypertension.
      Agents which depress the myocardium should be avoided (an opiate technique is
      preferable to a technique based on volatile agents). Agents which cause a
      tachycardia should be avoided. Controlled ventilation is safer than spontaneous
      ventilation. Appropriate monitoring is essential in every case.

PMID- 8289744
TI  - Congenital heart disease: Anesthetic considerations in non-cardiac surgery.

PMID- 8289745
TI  - Anesthetic management of pregnant patients with cardiac disease.

PMID- 8289746
TI  - Management of perioperative dysrhythmias.
AB  - This paper reviews cardiac dysrhythmias occurring in the perioperative period.
      Electrocardiography was the first application of electronic monitoring to
      anesthesia care. The detection of dysrhythmias remains the most important use of
      this technology today. While the description of dysrhythmias dates back to the
      early 1900's, the first large series was reported in 1936. Early descriptions of
      the kinds seen and the predisposing factors have changed little in the past 50
      years. Several factors tend to emerge when one evaluates perioperative
      dysrhythmias. These are the anesthetic given, the site of surgery, abnormalities
      of blood gases or electrolytes, tracheal intubation, reflexes such as vagal
      slowing and the oculocardiac reflex, stimulation of the central nervous system
      the presence of pre-existing heart disease, and the use of intracardiac devices.
      In the evaluation of cardiac dysrhythmias several facts need to be determined.
      The most important is to determine if there is an underlying complication of
      anesthesia and surgery which may explain the dysrhythmia. In addition, one needs
      to evaluate the heart rate, the regularity, the number of P waves per QRS, and
      the configurations of the QRS. The anesthesiologist needs to determine whether
      the rhythm is dangerous to the patient and whether it requires treatment. The two
      major abnormalities of sinus rhythm are sinus bradycardia and the sinus
      tachycardia. Sinus bradycardia can be due to hypoxia, vagal stimulation, drug
      effects, a high sympathetic block or an acute myocardial infarction. Sinus
      tachycardia can be due pain, light anesthesia, hypovolemia, sepsis, hypoxia,
      hypercapnia and drug effects. The major atrial dysrhythmias are paroxysmal atrial
      tachycardia, atrial fibrillation and atrial flutter. Each require treatment if
      perfusion is impaired or if the heart rate is persistently elevated. The new
      agents esmolol and adenosine are particularly useful in managing atrial
      dysrhythmias. The major ventricular dysrhythmias are ventricular premature
      contractions, ventricular tachycardia and ventricular fibrillation. The later two
      demand emergency management with DC cardioversion when perfusion is impaired. The
      major abnormality of conduction is complete heart block which usually requires
      emergency treatment in the perioperative period. Prompt evaluation and management
      of perioperative dysrhythmias reduce anesthetic morbidity and mortality.

PMID- 8289747
TI  - Hypertension: has anything changed for the anesthetist?

PMID- 8289748
TI  - The anesthesiologist's role in cardiac transplantation.
AB  - Cardiac transplantation has become an increasingly common operation and many
      patients who have transplanted hearts may require anesthetic care at any time.
      Management of the recipient is similar to managing any patient with severe
      cardiac failure before the new heart is implanted. Following transplantation the
      problems are those of the denervated heart and the problems associated with the
      immunosuppressive agents used for transplantation.

PMID- 8289749
TI  - Effects of heart rate, blood pressure and bronchomotor tone of halothane,
      enflurane and isoflurane in young fit patients.
AB  - A prospective study was undertaken on 169 healthy young patients undergoing
      elective ear, nose and throat surgery to assess the intraoperative effects on
      heart rate, blood pressure and bronchomotor tone of MAC in nitrous oxide
      concentrations of halothane (0.4 to 0.6%), isoflurane (0.6 to 0.8%) and enflurane
      (0.8 to 1%). All the agents produced a progressive slowing of the heart rate
      during anesthesia. Halothane did so most profoundly, resulting in a maximum
      slowing of 40 beats-1 compared with a maximum slowing of about 20 beats min-1
      with both isoflurane and enflurane. The three volatile agents also produced
      progressively similar degrees of hypotension during anesthesia. The hypotension
      produced by enflurane occurred earliest and was most profound; that produced by
      isoflurane occurred less early and was less severe, but occurred earlier and was
      more severe than that produced by halothane. Neither halothane, isoflurane nor
      enflurane appeared to have any effect on bronchomotor tone.

PMID- 8289750
TI  - New modes of ventilation.

PMID- 8289751
TI  - [Pathogenesis of diabetic microangiopathy].
AB  - Several are the recent experimental data regarding the pathogenesis of diabetic
      microangiopathy, even if the comprehensive picture of this condition is still
      rather incomplete. The functional and structural alterations of several organs
      involved (first of all kidney and retina) are especially dependent on the
      activation of the polyol pathway and on the increase of the nonenzymatic
      glycosylation. An important determinant of diabetic microangiopathy is the
      increase of permeability, at first charged especially to the haemodynamic
      alterations and partly reversible, and later supported by irreversible variations
      of the cellular and extracellular components of the vascular wall. Genetic
      factors certainly contribute to the explanation of the diverse gravity of
      microvascular damage in diabetic patients, even if the mechanisms by which they
      interfere are only partly known. Furthermore, the links between arterial
      hypertension and diabetic nephropathy, and also the reduction in
      glycosaminoglycans in the basal membranes are perhaps genetically originated.

PMID- 8289752
TI  - [Treatment of hot thyroid nodule with percutaneous ethanol injection. Our
      experience].
AB  - Thyroid nodule is defined as "hot" on the bous it scintigraphic appearance. It
      can be defined like benign nodule with autonomous functionality. On scintiscan it
      shows high captation because there's an increase of production and secretion of
      thyroid hormones with total inhibition of TSH and suppression of extranodular
      tissue. Generally the treatment of hot thyroid nodule was surgical or with radio
      metabolic therapy. Percutaneous ethanol injection (PEI) in the treatment of hot
      thyroid nodules has been suggested recently. The aim of our study was to value
      therapeutic effects of PEI under guidance by means of ultrasound in patients with
      hot nodules in toxic or pretoxic phase. 36 patients with autonomous thyroid
      nodules of 1.8-6 cm in diameter received sterile ethanol at 95% that has been
      injected with a 22-gauge needle and a probe with a guide device. The
      administrated dose varied from 1.2 to 1.5 ml for cc of tissue in 5-12 sessions.
      Ethanol injection was performed in a single site in nodules with diameter < 3 cm
      and in double sites in nodules with diameter > 3 cm. The patients were checked
      after treatment and then 3 and 6 months. Our experience confirms an excellent
      response to PEI in these patients. In fact after therapy symptoms of
      hyperthyroidism and hormonal levels become normal; no patient has even reached
      the range of subclinical or clinical hypothyroidism. Scintigram showed that
      previously suppressed thyroid tissue resumed functioning; at ultrasound all
      nodules had shrunk: thyroglobulin levels increased during treatment because
      ethanol induces coagulative intranodular necrosis with release in systemic
      circulation of this glycoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289753
TI  - [Hashimoto's thyroiditis and HLA in Caucasian Italians].
AB  - Sixty cases of goitrous Hashimoto's thyroiditis were observed at the first
      diagnosis. For 18 of the cases, the diagnosis was made only on the basis of
      cytological examination since antithyroid antibodies were always negative. To
      determine if seronegative or seropositive forms constituted a particular
      genetically determined subgroup, we evaluated whether such peculiarities were
      related to specific HLA haplotype. Analysis of HLA antigens showed in the
      seropositive a significant increase in the frequency of HLA-B51 and HLA-A2, a
      significant decrease in the frequency of HLA-A1 and HLA-DR1. In seronegative
      cases no increase was found in the frequency of HLA-A-B-DR antigens, but they
      showed a strong positive association with HLA-DQ3. Our results show that
      association of Hashimoto's thyroiditis with HLA antigens was different in
      seronegative and seropositive subgroup. This finding would seem to support the
      hypothesis that in a few subjects the entire immune process develops exclusively
      within the involved organ and this process would be genetically determined.

PMID- 8289754
TI  - [The effect of GH on erythropoiesis in vivo].
AB  - It has been demonstrated that the direct and/or indirect stimulation of
      hematopoiesis is one of the effects of the growth hormone (GH) in vitro. In order
      to study the effect of GH on erythropoiesis in vivo, the variation of hemochrome
      in a group of 8 subjects with GH deficiency (GHD) were monitored during a
      substitutive therapy with biosynthetic GH (rhGH) at dose of 0.4 U/kg/week.
      Hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), number of red
      blood cells (RBC) were analysed in all subjects at the beginning and after 9
      months of treatment. The effectiveness of therapy was demonstrated by
      statistically significant variations in height, height SDS, growth velocity,
      serum levels of IGF-I. After 9 months of rhGH therapy, a significant increase was
      observed in all values considered with exception of MCV. In conclusion Gh would
      appear to stimulate erythropoiesis, directly or indirectly, and these results
      would appear to indicate an in vivo confirmation.

PMID- 8289755
TI  - [Adrenal myelolipoma. Historical, etiopathogenetic, pathologic, clinical,
      epidemiologic and radiologic features. A case report].
AB  - Adrenal myelolipoma is a rare, benign, non-functional tumor composed of fat and
      brown erythropoietic marrow in varying proportions. It is a rare clinical entity.
      Usually asymptomatic, in the majority of cases it is found incidentally at
      autopsy. The authors discuss the historical, etiopathogenetic, anatomo
      pathological, clinical-epidemiological and radiological features. They also
      describe a case of myelolipoma of the right adrenal gland come to their
      observation.

PMID- 8289756
TI  - [Microprolactinoma and rheumatoid arthritis. A case of rheumatoid-like
      polyarthritis].
AB  - A case of the rheumatoid-like polyarthritis-associated microprolactinoma is
      described. Its main clinical features are underlined, and its possible pathogenic
      mechanisms are reported.

PMID- 8289757
TI  - The potential use of parenteral dipeptides in clinical nutrition.
AB  - The metabolic effects of intravenous peptides have undergone extensive
      investigation in recent years. Dipeptide solutions provide a mechanism for the
      provision of selected amino acids that may be conditionally indispensable under
      certain clinical conditions. In particular, amino acids such as cystine,
      glutamine, and tyrosine may be difficult to provide in their free form, but their
      availability can be increased substantially when they are supplied in the form of
      a dipeptide. Animal and human studies have demonstrated that parenteral
      dipeptides are cleared rapidly from the plasma compartment and favorably
      influence nitrogen equilibrium in healthy volunteers and catabolic patients.
      Certain dipeptides offer the potential for tailoring tissue-specific nutrition
      therapy. It seems likely that parenteral peptides will offer a major change in
      the delivery of intravenous nutrients.

PMID- 8289758
TI  - Treatment of anorexia with megestrol acetate.
AB  - Anorexia and involuntary weight loss are prevalent problems in oncology and AIDS
      patients. Cytokines are suspected but not proven causes of cachexia. Megestrol
      acetate has been found to increase appetite, food intake, and weight in
      randomized, placebo-controlled trials in patients with advanced malignancies and
      in patients with AIDS. This hormone derivative probably has both central nervous
      system and peripheral metabolic effects. No significant effect on survival has
      been demonstrated in these trials. The optimal dose for appetite enhancement is
      unknown; we have chosen 320 mg/d as our initial dose. Megestrol acetate is
      usually well tolerated, and it may be helpful in the symptomatic and palliative
      therapy of patients with anorexia and weight loss.

PMID- 8289759
TI  - Causes of diarrhea in tube-fed patients: a comprehensive approach to diagnosis
      and management.
AB  - In the absence of a standard definition for diarrhea, clinicians have developed
      their own descriptions, such as an increased frequency of stools, an increased
      quantity of water in the stool, an increased weight of the stool, or a change in
      the consistency of the stool. The clinician should first determine whether the
      diarrhea is osmotic or secretory. Diarrhea in patients who receive enteral
      nutrition is often caused by such conditions as diabetes, malabsorption
      syndromes, infection, gastrointestinal complications, or concomitant drug therapy
      instead of the enteral formula. Factors related to the enteral nutrition that may
      contribute to diarrhea include the composition of the formula, the manner of
      administration, or bacterial contamination. To ensure that the nutritional
      requirements of patients are met and the appropriate treatment is administered,
      all of the possible causes of diarrhea should be considered before discontinuing
      or reducing the amount of formula delivered.

PMID- 8289760
TI  - Standards for nutrition support pharmacists. American Society for Parenteral and
      Enteral Nutrition.

PMID- 8289761
TI  - Interested voices: who's speaking for nutrition?

PMID- 8289762
TI  - From keynote to coalition: formation of the coalition for nutrition services in
      health care reform.

PMID- 8289763
TI  - Method of achieving postpyloric placement of weighted feeding tubes.

PMID- 8289764
TI  - Intravenous peptides.

PMID- 8289765
TI  - Dipeptides in parenteral nutrition: from basic science to clinical applications.
AB  - The use of intravenous dipeptides shows great promise as an avenue for the
      provision of amino acids that may otherwise be difficult to deliver via nutrient
      infusions. The physical/chemical properties and metabolism of numerous dipeptides
      have now been explored in experimental and human studies. It has been found that
      these agents have the capacity to spare nitrogen and support serum protein levels
      in a fashion equivalent to that of intravenous free amino acids. An additional
      benefit is the ability to deliver certain amino acids that are relatively
      unstable or poorly soluble in aqueous solutions. These various aspects of
      intravenous dipeptides are considered in this review.

PMID- 8289766
TI  - Complications in vascular access devices.

PMID- 8289767
TI  - Vascular access devices: perspectives on designs, complications, and management.
AB  - The use of vascular access devices in hospitalized and home care patients has
      expanded rapidly in the past decade. New designs, materials, insertion
      techniques, and protocols for care related to vascular access devices have
      emerged. Complications associated with them, however, have remained a persistent
      problem. Septicemia, thrombosis, and occlusion are three of the more serious
      complications that can lead to the need for removal of the device. These
      complications are reviewed and areas for future research are identified.

PMID- 8289768
TI  - Principles of nutrition therapy for short-bowel syndrome.
AB  - Short-bowel syndrome is characterized by maldigestion, malabsorption,
      dehydration, electrolyte abnormalities, and both macronutrient and micronutrient
      deficiencies. Nutritional and hydration status are difficult to maintain without
      the provision of specialized nutrition support when more than 75% of the small
      intestine has been resected. Each patient's response to small-bowel resection is
      unique; therefore, the type of therapy must be tailored to each individual's
      bowel resection, complications that ensue, and specific nutrient needs. Clinical
      management should be guided by principles of nutrition assessment and treatment
      of nutrient deficiencies as well as routine monitoring of the patient's clinical
      course and response to therapy.

PMID- 8289769
TI  - Detection and prevention of central venous catheter-related infections.
AB  - Infectious complications of central venous catheterization are an important
      clinical problem. Although systemic infection complicates only a small fraction
      of cases, the prevalence of catheter-related sepsis remains high because of the
      widespread use of these catheters in acutely ill hospitalized patients. The major
      route of infection is probably by migration of microorganisms from the skin along
      the outer surface of the catheter and through the subcutaneous catheter tract to
      the bloodstream. Semi-quantitative catheter tip cultures have become a standard
      clinical tool for the evaluation for catheter-related infection. Despite the use
      of this technique and a variety of other proposed methods for evaluating catheter
      colonization and infection, discriminating catheter-related sepsis from sepsis
      originating at another site is often difficult. Prevention of these infections is
      important. There have been many investigations of the factors that contribute to
      catheter infections. These studies have shown that meticulous attention to
      sterile technique during catheter insertion and during routine maintenance is
      critical.

PMID- 8289770
TI  - Nutrition screening: identifying patients at risk for malnutrition.
AB  - Studies have identified malnutrition as a common problem among many hospitalized
      patients. Malnutrition can adversely affect a patient's response to treatment,
      prolonging recovery time. Nutrition screening is a process that can be initiated
      early in a patient's hospital stay to identify people who may be at risk for
      malnutrition. Early identification of these patients can help nutrition
      professionals focus their efforts on those who would benefit most. Clinical,
      biochemical, anthropometric, and dietary indicators should be included in a
      screening program to ensure optimal effectiveness. Screening programs can be
      developed with minimal effort by using existing staff and data readily available
      in a patient's medical record. This article describes one such screening program.

PMID- 8289771
TI  - Basic concepts of immunology and its application to clinical nutrition.
AB  - In recent years, evidence has accumulated on the effects of nutrients on
      metabolic processes. The role of specific nutrients in modulating immune function
      has received much attention because of the significant role of the immune system
      in a variety of disease states. The immune system depends on the complex
      interactions of its various parts. In response to an "antigen" or foreign
      substance that penetrates the external protective barriers of the human body,
      nonspecific (phagocytes, complement) defense mechanisms and antigen-specific
      factors are activated. The antigen-specific immune system relies on both humoral
      (antibodies and B cells) and cellular (T cells and lymphokines) defenses.
      Malnutrition causes a decline in all aspects of host defense. Correction of
      malnutrition in hospitalized patients and restoration of immunocompetence has
      become a goal of nutrition support practitioners today. The application of
      current research findings to patient care requires a basic understanding of
      immunology.

PMID- 8289772
TI  - Managed mental health for children and adolescents.

PMID- 8289773
TI  - Managed mental health, Medicaid, and medical cost offset.

PMID- 8289774
TI  - Managed mental health in the Oregon Health Plan.

PMID- 8289775
TI  - Health reform and organized systems of care.

PMID- 8289776
TI  - Alcan aluminum: development of a mental health "carve-out".
AB  - This comprehensive approach may be unusual for a company of Alcan's size.
      Clearly, it is a progressive, thorough, and multilevel strategy that did the
      following: recognized the cost impact and quality-of-care defects in the previous
      benefit plans; was ready to manage the medical plans, especially the MHSA benefit
      plan; used a careful diagnostic approach, including data analysis, plan design
      review, and input from many constituencies; developed a custom-designed program,
      bid, and vendor selection process; avoided shifting costs to employees; kept
      benefit levels adequate; kept employees satisfied; recognized that employees can
      be under stress and offered a way to provide assistance; and creatively addressed
      the increasing diversity in the workforce.

PMID- 8289777
TI  - Managed mental health care in the public sector.
AB  - Due to strong market forces and payor concerns, first in the private and now in
      the public sector, the mental health field is changing. The survivors and leaders
      will be the innovators and risk takers. They must have the ability to look
      critically at themselves and make needed changes. This new environment creates
      great opportunity to provide better mental health care. Capitated mental health
      programs for Medicaid beneficiaries are developing in various forms across the
      country, and mental health providers, both private and public, need to be aware
      of those developments. Such programs have great promise for community mental
      health centers. Medicaid is generally a major funding source for the community
      mental health system, and public funds should be used to the best extent
      possible. Managed care has great promise for cost containment and can provide
      financial stability for community mental health centers. The most important
      promise of managed care, however, is improving access to and quality of mental
      health services for the Medicaid population.

PMID- 8289778
TI  - Managed care: a provider perspective.

PMID- 8289779
TI  - Community mental health and managed care.
AB  - CMHOs are the heirs to a rich tradition of coordinated and comprehensive services
      and appropriate clinical outcomes in the least restrictive settings. The early
      CMHO focus on prevention, coordination of services, continuity of care, and
      partial and residential services, as well as psychosocial and case management
      methodologies, underlies contemporary managed behavioral health programs. This
      provides CMHOs with a great opportunity to be major participants in the new
      programs.

PMID- 8289780
TI  - Substance abuse and managed care.
AB  - Substance abuse by the late 1980s had already become a prominent, out-of-control
      sector of health care. Some of the reasons for this crisis, as well as more
      recent changes in this specialty field, are explicated in this chapter.

PMID- 8289781
TI  - Use of double-replacement gene targeting to replace the murine alpha-lactalbumin
      gene with its human counterpart in embryonic stem cells and mice.
AB  - The mouse alpha-lactalbumin gene has been replaced with the human gene by two
      consecutive rounds of gene targeting in hypoxanthine phosphoribosyltransferase
      (HPRT)-deficient feeder-independent murine embryonic stem (ES) cells. One mouse
      alpha-lactalbumin allele was first replaced by an HPRT minigene which was in turn
      replaced by human alpha-lactalbumin. The end result is a clean exchange of
      defined DNA fragments with no other DNA remaining at the target locus. Targeted
      ES cells at each stage remained capable of contributing efficiently to the germ
      line of chimeric animals. Double replacement using HPRT-deficient ES cells and
      the HPRT selection system is therefore a powerful and flexible method of
      targeting specific alterations to animal genes. A typical strategy for future use
      would be to generate a null mutation which could then be used to produce multiple
      second-step alterations at the same locus.

PMID- 8289782
TI  - Cloning and characterization of KNR4, a yeast gene involved in (1,3)-beta-glucan
      synthesis.
AB  - k9 killer toxin from Hansenula mrakii was used to select a number of resistant
      mutants from Saccharomyces cerevisiae. Preliminary biochemical and genetic
      studies showed that some of them acquired structural defects in the cell wall.
      One of these mutants, the knr4-1 mutant, displays a number of cell wall defects,
      including osmotic sensitivity; sensitivity to cercosporamide, a known antifungal
      agent; and resistance to Zymolyase, a (1,3)-beta-glucanase. We report here the
      isolation and analysis of the KNR4 gene. DNA sequence analysis revealed an
      uninterrupted open reading frame which contains five potential start codons. The
      longest coding template encodes a protein of 505 amino acids with a calculated
      molecular mass of 57,044 Da. A data base search revealed 100% identity with a
      nuclear protein, SMI1p. Disruption of the KNR4 locus does not result in cell
      death; however, it leads to reduced levels of both (1,3)-beta-glucan synthase
      activity and (1,3)-beta-glucan content in the cell wall. The gene was mapped to
      the right arm of chromosome VII.

PMID- 8289783
TI  - Retinoic acid represses Oct-3/4 gene expression through several retinoic acid
      responsive elements located in the promoter-enhancer region.
AB  - The Oct-3/4 gene product, which belongs to the POU family of transcription
      factors, is a good candidate for regulating initial differentiation decisions. It
      is expressed in the earliest stages of embryogenesis and repressed in subsequent
      stages. Retinoic acid (RA)-induced differentiation of embryonal carcinoma (EC)
      cells is accompanied by decreased expression of the Oct-3/4 gene. Previous
      findings show that sequences in the Oct-3/4 enhancer region (designated RARE1)
      are targets for RA-mediated repression (H. Okazawa, K. Okamoto, F. Ishino, T.
      Ishino-Kaneko, S. Takeda, Y. Toyoda, M. Muramatsu, and H. Hamada, EMBO J. 10:2997
      3005, 1991). Our present results demonstrate conclusively that the TATA-less Oct
      3/4 promoter is also a target for RA-induced repression. We identified a novel
      cis element in the Oct-3/4 promoter harbors a putative Sp1 binding site and a RA
      responsive element (designated RAREoct), which are juxtaposed to one another.
      Protein binding to the Sp1 site is independent of protein binding to the RAREoct
      sequence. Unlike the RARE1 situated in the Oct-3/4 enhancer which does not
      contain a typical RAR recognition site, the RAREoct identified in this study
      consists of three directly repeated motifs that exhibit extensive homology to
      RARE sequences located in RA-responsive genes. Moreover, the RAREoct shows
      different DNA-binding characteristics and DNase I footprint patterns with nuclear
      proteins isolated from undifferentiated versus RA-differentiated EC cells. This
      suggests that the RAREoct element binds different nuclear proteins in RA-treated
      and untreated EC cells which most probably belong to the RA receptor, retinoid X
      receptor, or orphan receptor families of transcription factors. Using site
      directed mutagenesis, we show that the RAREoct contributes to the transcriptional
      activation of Oct-3/4 promoter in P19 cells and, most interestingly, mediates the
      RA-induced repression in RA-differentiated EC cells. Thus, the RAREoct element
      could be one of the points of integration of several signalling pathways
      influencing Oct-3/4 expression. In accordance with the suggestion that
      suppression of Oct-3/4 expression is a crucial step during embryogenesis, the Oct
      3/4 upstream region contains multiple targets for RA-induced repression, probably
      to ensure accurate and prompt repression of Oct-3/4 expression. It is possible
      that these repressors are differentially used at specific stages of development
      in response to various signals.

PMID- 8289784
TI  - Differential regulation of the c-myc oncogene promoter by the NF-kappa B rel
      family of transcription factors.
AB  - The murine c-myc gene contains two elements responsive to the rel-oncogene
      related family of NF-kappa B factors. Previously we have shown that factor
      binding to these two NF-kappa B elements mediates induction of transcription of
      the c-myc promoter upon interleukin-1 treatment of human dermal fibroblasts and
      human T-cell leukemia virus type I tax gene expression in T cells (D. J. Kessler,
      M. P. Duyao, D. B. Spicer, and G. E. Sonenshein, J. Exp. Med. 176:787-792, 1992;
      M. P. Duyao, D. J. Kessler, D. B. Spicer, C. Bartholomew, J. L. Cleveland, M.
      Siekevitz, and G. E. Sonenshein, J. Biol. Chem. 267:16288-16291, 1992). To begin
      to delineate the specific roles of the individual members of the NF-kappa B
      family, here we have tested their effects on activation of a c-myc promoter/exon
      1-CAT construct in NIH 3T3 cells. Classical NF-kappa B (p65/p50) was a potent
      transcriptional activator of the c-myc promoter. Cotransfection with either p65
      alone or p65 in combination with p50 mediated significant induction. In contrast,
      expression of either v-rel or chicken c-rel failed to transactivate, while murine
      c-rel induced c-myc promoter activity only slightly. Furthermore, induction by
      classical NF-kappa B was inhibited by coexpression of either v-rel or chicken c
      rel. Thus, individual members of the rel family have differential effects of the
      c-myc promoter, which can modulate overall transcriptional activity and allow for
      precise regulation of this oncogene under diverse physiologic conditions.

PMID- 8289785
TI  - Interactions among three proteins that specifically activate translation of the
      mitochondrial COX3 mRNA in Saccharomyces cerevisiae.
AB  - The PET54, PET122, and PET494 proteins, which are associated with the yeast inner
      mitochondrial membrane, specifically activate translation of the mitochondrially
      encoded COX3 mRNA. We used the two-hybrid system to test whether pairs of these
      proteins, when fused to either the GAL4 DNA-binding or transcriptional activating
      domain, can physically associate as measured by the expression of the GAL4
      dependent reporter, lacZ. PET54 and PET122 interacted in this system, and an
      amino-terminally truncated PET494 fragment showed an interaction with PET54. We
      also detected functional interactions between PET54 and PET122 genetically: a
      pet54 missense substitution (Phe to Gly at position 244) that caused a severe
      respiratory defect was suppressed both by a missense substitution affecting
      PET122 (Gly to Val at position 211) and by overproduction of wild-type PET122.
      Both Gly and Ala, substituted at PET54 position 244, disrupted the two-hybrid
      interactions with PET122 and PET494. While Ala at PET54 position 244 caused only
      a modest respiratory phenotype alone, it caused a severe respiratory defect when
      combined with a cold-sensitive mitochondrial mutation affecting the COX3 mRNA 5'
      leader. This synthetic defect was suppressed by a missense substitution in PET122
      and by overproduction of wild-type PET122, indicating functional interactions
      among PET54, PET122, and the mRNA. Taken together with previous work, these data
      suggest that a complex containing PET54, PET122, and PET494 mediates the
      interaction of the COX3 mRNA with mitochondrial ribosomes at the surface of the
      inner membrane.

PMID- 8289786
TI  - Mutational activation of the STE5 gene product bypasses the requirement for G
      protein beta and gamma subunits in the yeast pheromone response pathway.
AB  - The STE5 gene encodes an essential element of the pheromone response pathway
      which is known to act either after the G subunit encoded by the STE4 gene or at
      the same step. Mutations in STE5, designated STE5Hyp, that partially activate the
      pathway in the absence of pheromone were isolated. One allele (STE5Hyp-2) was
      shown to cause a single amino acid substitution near the N terminus of the
      predicted STE5 protein. Immunoblotting with anti-Ste5 antibodies indicated that
      the phenotype was not due to an increased level of the mutant STE5 protein. A
      multicopy episomal plasmid containing a STE5Hyp allele partially suppressed both
      the block in pheromone-inducible transcription and the sterility phenotype caused
      by null alleles of the STE2, STE4, or STE18 gene, indicating that the STE5
      product acts after the receptor (STE2 product) and after the G protein beta and
      gamma subunits (STE4 and STE18 products, respectively). However, the phenotypes
      of the STE5Hyp mutations were less pronounced in ste4 and ste18 mutants,
      suggesting that the STE5Hyp-generated signal partially depends on the proposed G
      beta gamma complex. The STE5Hyp alleles did not suppress ste7, ste11, ste12, or
      fus3 kss1 null mutants, consistent with previous findings that the STE5 product
      acts before the protein kinases encoded by STE7, STE11, FUS3, and KSS1 and the
      transcription factor encoded by STE12. The mating defects of the ste2 deletion
      mutant and the temperature-sensitive ste4-3 mutant were also suppressed by
      overexpression of wild-type STE5. The slow-growth phenotype manifested by cells
      carrying STE5Hyp alleles was enhanced by the sst2-1 mutation; this effect was
      eliminated in ste4 mutants. These results provide the first evidence that the
      STE5 gene product performs its function after the G protein subunits.

PMID- 8289787
TI  - Anisomycin and rapamycin define an area upstream of p70/85S6k containing a
      bifurcation to histone H3-HMG-like protein phosphorylation and c-fos-c-jun
      induction.
AB  - Anisomycin, a translational inhibitor, synergizes with growth factors and phorbol
      esters to superinduce c-fos and c-jun by a number mechanisms, one of which is its
      ability to act as a potent signalling agonist, producing strong, prolonged
      activation of the same nuclear responses as epidermal growth factor or
      tetradecanoyl phorbol acetate. These responses include the phosphorylation of
      pp33, which exists in complexed and chromatin-associated forms, and of histone H3
      and an HMG-like protein. By peptide mapping and microsequencing, we show here
      that pp33 is the phosphoprotein S6, present in ribosomes and in preribosomes in
      the nucleolus. Ablation of epidermal growth factor-, tetradecanoyl phorbol
      acetate-, or anisomycin-stimulated S6 phosphorylation by using the p70/85S6k
      inhibitor rapamycin has no effect on histone H3 and HMG-like protein
      phosphorylation or on the induction and superinduction of c-fos and c-jun.
      Further, [35S]methionine-labelling and immunoprecipitation studies show that the
      ablation of S6 phosphorylation has no discernible effect on translation in
      general or translation of newly induced c-fos transcripts. Finally, we show that
      anisomycin augments and prolongs S6 phosphorylation not by blocking S6
      phosphatases but by sustained activation of p70/85S6k. These results suggest the
      possible use of anisomycin and rapamycin to define upstream and downstream
      boundaries of an area of signalling above p70/85S6k which contains a bifurcation
      that produces histone H3-HMG-like protein phosphorylation and c-fos-c-jun
      induction in the nucleus.

PMID- 8289788
TI  - Cdc42p GTPase is involved in controlling polarized cell growth in
      Schizosaccharomyces pombe.
AB  - Cdc42p is a highly conserved low-molecular-weight GTPase that is involved in
      controlling cellular morphogenesis. We have isolated the Cdc42p homolog from the
      fission yeast Schizosaccharomyces pombe by its ability to complement the
      Saccharomyces cerevisiae cdc42-1ts mutation. S. pombe Cdc42p is 85% identical in
      predicted amino acid sequence to S. cerevisiae Cdc42p and 83% identical to the
      human Cdc42p homolog. The Cdc42p protein fractionates to both soluble and
      particulate fractions, suggesting that it exists in two cellular pools. We have
      disrupted the cdc42+ gene and shown that it is essential for growth. The cdc42
      null phenotype is an arrest as small, round, dense cells. In addition, we have
      generated three site-specific mutations, G12V, Q61L, and D118A, in the Cdc42p GTP
      binding domains that correspond to dominant-lethal mutations in S. cerevisiae
      CDC42. In contrast to the S. cerevisiae cdc42 mutations, the S. pombe cdc42
      mutant alleles were not lethal when overexpressed. However, the cdc42 mutants did
      exhibit an abnormal morphological phenotype of large, misshapen cells, suggesting
      that S. pombe Cdc42p is involved in controlling polarized cell growth.

PMID- 8289789
TI  - Specific expression of the human CD4 gene in mature CD4+ CD8- and immature CD4+
      CD8+ T cells and in macrophages of transgenic mice.
AB  - The CD4 protein plays a critical role in the development and function of the
      immune system. To gain more insight into the mechanism of expression of the human
      CD4 gene, we cloned 42.2 kbp of genomic sequences comprising the CD4 gene and its
      surrounding sequences. Studies with transgenic mice revealed that a 12.6-kbp
      fragment of the human CD4 gene (comprising 2.6 kbp of 5' sequences upstream of
      the transcription initiation site, the first two exons and introns, and part of
      exon 3) contains the sequences required to support the appropriate expression in
      murine mature CD4+ CD8- T cells and macrophages but not in immature double
      positive CD4+ CD8+ T cells. Expression in CD4+ CD8+ T cells was found to require
      additional regulatory elements present in a T-cell enhancer fragment recently
      identified for the murine CD4 gene (S. Sawada and D. R. Littman, Mol. Cell. Biol.
      11:5506-5515, 1991). These results suggest that expression of CD4 in mature and
      immature T-cell subsets may be controlled by distinct and independent regulatory
      elements. Alternatively, specific regulatory elements may control the expression
      of CD4 at different levels in mature and immature T-cell subsets. Our data also
      indicate that mouse macrophages contain the regulatory factors necessary to
      transcribe the human CD4 gene.

PMID- 8289790
TI  - Ig alpha and Ig beta are functionally homologous to the signaling proteins of the
      T-cell receptor.
AB  - Signal transduction by antigen receptors and some Fc receptors requires the
      activation of a family of receptor-associated transmembrane accessory proteins.
      One common feature of the cytoplasmic domains of these accessory molecules is the
      presence is at least two YXXA repeats that are potential sites for interaction
      with Src homology 2 domain-containing proteins. However, the degree of similarity
      between the different receptor-associated proteins varies from that of T-cell
      receptor (TCR) zeta and Fc receptor RIIIA gamma chains, which are homologous, to
      the distantly related Ig alpha and Ig beta proteins of the B-cell antigen
      receptor. To determine whether T- and B-cell antigen receptors are in fact
      functionally homologous, we have studied signal transduction by chimeric
      immunoglobulins bearing the Ig alpha or Ig beta cytoplasmic domain. We found that
      Ig alpha and Ig beta cytoplasmic domains were able to activate Ca2+ flux,
      interleukin-2 secretion, and phosphorylation of the same group of cellular
      substrates as the TCR in transfected T cells. Chimeric proteins were then used to
      examine the minimal requirements for activation of the Fyn, Lck, and ZAP kinases
      in T cells. Both Ig alpha and Ig beta were able to trigger Fyn, Lck, and ZAP
      directly without involvement of TCR components. Cytoplasmic tyrosine residues in
      Ig beta were required for recruitment and activation of ZAP-70, but these amino
      acids were not essential for the activation of Fyn and Lck. We conclude that Fyn
      and Lck are able to recognize a clustered nonphosphorylated immune recognition
      receptor, but activation of these kinases is not sufficient to induce cellular
      responses such as Ca2+ flux and interleukin-2 secretion. In addition, the
      molecular structures involved in antigen receptor signaling pathways are
      conserved between T and B cells.

PMID- 8289791
TI  - Identification of residues of the H-ras protein critical for functional
      interaction with guanine nucleotide exchange factors.
AB  - Ras proteins are activated in vivo by guanine nucleotide exchange factors encoded
      by genes homologous to the CDC25 gene of Saccharomyces cerevisiae. We have taken
      a combined genetic and biochemical approach to probe the sites on Ras proteins
      important for interaction with such exchange factors and to further probe the
      mechanism of CDC25-catalyzed GDP-GTP exchange. Random mutagenesis coupled with
      genetic selection in S. cerevisiae was used to generate second-site mutations
      within human H-ras-ala15 which could suppress the ability of the Ala-15
      substitution to block CDC25 function. We transferred these second-site suppressor
      mutations to normal H-ras and oncogenic H-rasVal-12 to test whether they induced
      a general loss of function or whether they selectively affected CDC25
      interaction. Four highly selective mutations were discovered, and they affected
      the surface-located amino acid residues 62, 63, 67, and 69. Two lines of evidence
      suggested that these residues may be involved in binding to CDC25: (i) using the
      yeast two-hybrid system, we demonstrated that these mutants cannot bind CDC25
      under conditions where the wild-type H-Ras protein can; (ii) we demonstrated that
      the binding to H-Ras of monoclonal antibody Y13-259, whose epitope has been
      mapped to residues 63, 65, 66, 67, 70, and 73, is blocked by the mouse sos1 and
      yeast CDC25 gene products. We also present evidence that the mechanism by which
      CDC25 catalyzes exchange is more involved than simply catalyzing the release of
      bound nucleotide and passively allowing nucleotides to rebind. Most critically, a
      complex of Ras and CDC25 protein, unlike free Fas protein, possesses
      significantly greater affinity for GTP than for GDP. Furthermore, the Ras CDC25
      complex is more readily dissociated into free subunits by GTP than it is by GDP.
      Both of these results suggest a function for CDC25 in promoting the selective
      exchange of GTP for GDP.

PMID- 8289792
TI  - Identification of residues critical for Ras(17N) growth-inhibitory phenotype and
      for Ras interaction with guanine nucleotide exchange factors.
AB  - The Ras(17N) dominant negative antagonizes endogenous Ras function by forming
      stable, inactive complexes with Ras guanine nucleotide exchange factors (GEFs;
      e.g., SOS1). We have used the growth-inhibitory phenotype of Ras(17N) to
      characterize two aspects of Ras interaction with GEFs. First, we used a
      nonprenylated version of Ras(17N), designated Ras(17N/186S), which no longer
      associates with the plasma membrane and lacks the growth-inhibitory phenotype, to
      address the importance of Ras subcellular location and posttranslational
      modification for its interaction with GEFs. We observed that addition of an N
      terminal myristylation signal to Ras(17N/186S) restored the growth-inhibitory
      activity of nonprenylated Ras(17N). Thus, membrane association, rather than
      prenylation, is critical for Ras interaction with Ras GEFs. Second, we used a
      biological selection approach to identify Ras residues which are critical for
      Ras(17N) growth inhibition and hence for interaction with Ras GEFs. We identified
      mutations at residues 75, 76, and 78 that abolished the growth-inhibitory
      activity of Ras(17N). Since GEF interaction is dispensable for oncogenic but not
      normal Ras function, our demonstration that single-amino-acid substitutions at
      these three positions impaired the transforming activity of normal but not
      oncogenic Ras provides further support for the role of these residues in Ras-GEF
      interactions. Finally, Ras(WT) proteins with mutations at these residues were no
      longer activated by mammalian SOS1. Altogether, these results suggest that the
      Ras intracellular location and Ras residues 75 to 78 are critical for Ras-GEF
      interaction.

PMID- 8289793
TI  - Characterization of a negative retinoic acid response element in the murine Oct4
      promoter.
AB  - Expression of Oct4 in embryonic stem cells is controlled by a distal upstream
      stem cell-specific enhancer that is deactivated during retinoic acid (RA)-induced
      differentiation by an indirect mechanism not involving binding of RA receptors
      (H. Okazawa, K. Okamoto, F. Ishino, T. Ishino-Kaneko, S. Takeda, Y. Toyoda, M.
      Muramatsu, and H. Hamada, EMBO J. 10:2997-3005, 1991). Here we report that in RA
      treated P19 embryonal carcinoma cells the Oct4 promoter is also subject to
      negative regulation by RA. The minimal Oct4 promoter sequence mediating
      repression consists of a promoter-proximal sequence containing a GC-rich SP1
      consensus-like sequence and several hormone response element half-sites that can
      be arranged into direct repeats with different spacing. The GC box binds a
      nuclear factor that is invariably present in undifferentiated and RA-treated
      differentiated P19 cells. By contrast, the hormone response element-containing
      sequence binds factors that are induced following RA treatment. Mutational
      analysis and competition experiments show that the functional entity binding the
      RA-induced factor is a direct repeat sequence with a spacing of one nucleotide,
      previously shown to be a binding site for COUP transcription factors (COUP-TFs).
      Cotransfected orphan receptors COUP-TF1, ARP-1, and EAR-2 were able to repress
      the activity of Oct4 promoter-driven reporters in P19 EC cells, albeit with
      different efficiencies. Furthermore, the negative transcriptional effect of COUP
      TFs is dominant over the activating effect of the Oct4 embryonic stem cell
      specific enhancer. These results show that negative regulation of Oct4 expression
      during RA-induced differentiation of embryonic stem cells is controlled by two
      different mechanisms, including deactivation of the embryonic stem cell-specific
      enhancer and promoter silencing by orphan nuclear hormone receptors.

PMID- 8289794
TI  - The gene encoding a major component of the lateral elements of synaptonemal
      complexes of the rat is related to X-linked lymphocyte-regulated genes.
AB  - The lateral elements of synaptonemal complexes (SCs) of the rat contain major
      components with relative electrophoretic mobilities (M(r)S) of 30,000 and 33,000.
      After one-dimensional separation of SC proteins on polyacrylamide-sodium dodecyl
      sulfate gels, these components show up as two broad bands. These bands contain
      closely related proteins, as judged from their peptide maps and immunological
      reactivity. Using affinity-purified polyclonal anti-30,000- and anti-33,000-M(r)
      component antibodies, we isolated a cDNA encoding at least one of the 30,000- or
      33,000-M(r) SC components. The protein predicted from the nucleotide sequence of
      the cDNA, called SCP3 (for synaptonemal complex protein 3), has a molecular mass
      of 29.7 kDa and a pI value of 9.4. It has a potential nucleotide binding site and
      contains stretches that are predicted to be capable of forming coiled-coil
      structures. In the male rat, the gene encoding SCP3 is transcribed exclusively in
      the testis. SCP3 has significant amino acid similarity to the pM1 protein, which
      is one of the predicted products of an X-linked lymphocyte-regulated gene family
      of the mouse: there are 63% amino acid sequence similarity and 35% amino acid
      identity between the SCP3 and pM1 proteins. However, SCP3 differs from pM1 in
      several respects, and whether the proteins fulfill related functions is still an
      open question.

PMID- 8289795
TI  - Intracellular association of the protein product of the c-myc oncogene with the
      TATA-binding protein.
AB  - The c-myc proto-oncogene encodes nuclear phosphoproteins that bind DNA in a
      sequence-specific fashion and appear to function as transcriptional activators.
      Here we demonstrate that a 40-kDa nuclear protein coimmunoprecipitated with c-Myc
      specifically when nuclear proteins, extracted from nuclei of exponentially
      growing murine B-lymphoma WEHI 231 cells by using procedures for preparation of
      trans-acting factors, were reacted with anti-c-Myc antibodies made against
      different regions of the c-Myc protein. In contrast, preparation of nuclear
      lysates under denaturing conditions significantly reduced this coprecipitation.
      Upon incubation of WEHI 231 cells with the reversible chemical cross-linking
      agent dithiobis(succinimidyl propionate), the 40-kDa protein could be cross
      linked to c-Myc protein intracellularly. Identification of the 40-kDa protein as
      the TATA-binding protein (TBP) of the TFIID transcription initiation complex was
      made by comigration and V-8 protease mapping, which yielded identical peptide
      fragments upon digestion of the 40-kDa protein and material immunoprecipitated
      with an anti-TBP specific antibody. Furthermore, in vitro-translated TBP bound to
      the amino-terminal portion of c-Myc. Column chromatography of cross-linked
      nuclear proteins showed TBP to be in a large-molecular-weight complex with c-Myc,
      consistent with a transcription initiation complex. These results indicate that
      intracellularly, c-Myc interacts with TBP, suggesting a mechanism of interaction
      of this oncoprotein with the basal transcription machinery.

PMID- 8289796
TI  - Activation of the granulocyte-macrophage colony-stimulating factor promoter in T
      cells requires cooperative binding of Elf-1 and AP-1 transcription factors.
AB  - The granulocyte-macrophage colony-stimulating factor (GM-CSF) gene has been
      studied extensively as a model system of transcriptional induction during T
      lymphocyte activation. The GM-CSF gene is not expressed in resting peripheral
      blood T cells but is rapidly induced at the transcriptional level following
      activation through the cell surface T-cell receptor. A highly conserved 19-bp
      element located immediately 5' of the human GM-CSF TATA box (bp -34 to -52),
      herein called purine box 1 (PB1), has been shown to bind a T-cell nuclear protein
      complex and to be required for transcriptional induction of the GM-CSF gene
      following T-cell activation. The PB1 sequence motif is highly conserved in both
      human and murine GM-CSF genes. In this report, we demonstrate that the PB1
      element alone confers inducibility on a heterologous promoter following
      transfection into human Jurkat T cells. In addition, we identify a major PB1
      nuclear protein-binding complex that is not present in resting peripheral blood T
      cells but is rapidly induced following T-cell activation. Sequence analysis
      revealed that PB1 is composed of adjacent binding sites for Ets and AP-1
      transcription factors. In vitro mutagenesis experiments demonstrated that both
      the Ets and AP-1 sites are required for binding of the inducible PB1 nuclear
      protein complex and for the transcriptional activity of this element and the GM
      CSF promoter in activated T cells. Using antibodies specific for different Ets
      and AP-1 family members, we demonstrate that the major inducible PB1-binding
      activity present in activated T-cell nuclear extracts is composed of the Elf-1, c
      Fos, and JunB transcription factors. Taken together, these results suggest that
      cooperative interactions between specific Ets and AP-1 family members are
      important in regulating inducible gene expression following T-cell activation.

PMID- 8289797
TI  - Glucose repression of yeast mitochondrial transcription: kinetics of derepression
      and role of nuclear genes.
AB  - Yeast mitochondrial transcript and gene product abundance has been observed to
      increase upon release from glucose repression, but the mechanism of regulation of
      this process has not been determined. We report a kinetic analysis of this
      phenomenon, which demonstrates that the abundance of all classes of mitochondrial
      RNA changes slowly relative to changes observed for glucose-repressed nuclear
      genes. Several cell doublings are required to achieve the 2- to 20-fold-higher
      steady-state levels observed after a shift to a nonrepressing carbon source.
      Although we observed that in some yeast strains the mitochondrial DNA copy number
      also increases upon derepression, this does not seem to play the major role in
      increased RNA abundance. Instead we found that three- to sevenfold increases in
      RNA synthesis rates, measured by in vivo pulse-labelling experiments, do
      correlate with increased transcript abundance. We found that mutations in the
      SNF1 and REG1 genes, which are known to affect the expression of many nuclear
      genes subject to glucose repression, affect derepression of mitochondrial
      transcript abundance. These genes do not appear to regulate mitochondrial
      transcript levels via regulation of the nuclear genes RPO41 and MTF1, which
      encode the subunits of the mitochondrial RNA polymerase. We conclude that a
      nuclear gene-controlled factor(s) in addition to the two RNA polymerase subunits
      must be involved in glucose repression of mitochondrial transcript abundance.

PMID- 8289798
TI  - Physical and functional interaction between wild-type p53 and mdm2 proteins.
AB  - The mdm2 oncogene, which is often amplified in mammalian tumors, produces a
      number of transcripts that encode distinct protein forms. Previous studies
      demonstrating that overexpression of the mdm2 gene can activate its transforming
      potential, and can inhibit the transcriptional activation function of p53,
      prompted us to begin to explore possible functional differences among the various
      mdm2 products. Utilizing a transient transfection assay, we have evaluated four
      naturally occurring murine mdm2 forms for their ability to inhibit p53-mediated
      transcriptional activation of reporter genes regulated by p53 response elements.
      Three of these mdm2 forms were found to physically associate with the wild-type
      p53 protein and to possess the ability to inhibit its transactivation function. A
      fourth form failed to exhibit either of these functions. This last mdm2 form
      lacks the N-terminal protein domain that is present in the other three splice
      forms examined, pointing to this region as one that is critical for complex
      formation with the p53 protein. Identifying such differences among mdm2 proteins
      provides important clues for dissecting their functional domains, and emphasizes
      that defining the individual properties of these products will be critical in
      elucidating the overall growth control function of the mdm2 gene.

PMID- 8289799
TI  - Pigment-cell-specific genes from fibroblasts are transactivated after chromosomal
      transfer into melanoma cells.
AB  - Human and mouse fibroblast chromosomes carrying tyrosinase or b-locus genes were
      introduced, by microcell hybridization, into pigmented Syrian hamster melanoma
      cells, and the microcell hybrids were tested for transactivation of the
      fibroblast tyrosinase and b-locus genes. By using species-specific PCR
      amplification to distinguish fibroblast and melanoma cDNAs, it was demonstrated
      that the previously silent fibroblast tyrosinase and b-locus genes were
      transactivated following chromosomal transfer into pigmented melanoma cells.
      However, transactivation of the mouse fibroblast tyrosinase gene was unstable in
      microcell hybrid subclones and possibly dependent on a second fibroblast locus
      that could have segregated in the subclones. This second locus was not necessary
      for transactivation of the fibroblast b-locus gene, thus demonstrating
      noncoordinate transactivation of fibroblast tyrosinase and b-locus genes.
      Transactivation of the fibroblast tyrosinase gene in microcell hybrids apparently
      is dependent on the absence of a putative fibroblast extinguisher locus for
      tyrosinase gene expression, which presumably is responsible for the extinction of
      pigmentation in hybrids between karyotypically complete fibroblasts and melanoma
      cells.

PMID- 8289800
TI  - Stably integrated mouse mammary tumor virus long terminal repeat DNA requires the
      octamer motifs for basal promoter activity.
AB  - In the mouse mammary tumor virus promoter, a tandem of octamer motifs, recognized
      by ubiquitous and tissue-restricted Oct transcription factors, is located
      upstream of the TATA box and next to a binding site for the transcription factor
      nuclear factor I (NF-I). Their function was investigated with mutant long
      terminal repeats under different transfection conditions in mouse Ltk- cells and
      quantitative S1 nuclease mapping of the transcripts. In stable transfectants,
      which are most representative of the state of proviral DNA with respect to both
      number of integrated DNA templates and chromatin organization, a long terminal
      repeat mutant of both octamer sites showed an average 50-fold reduction of the
      basal transcription level, while the dexamethasone-stimulated level was
      unaffected. DNase I in vitro footprinting assays with L-cell nuclear protein
      extracts showed that the mutant DNA was unable to bind octamer factors but had a
      normal footprint in the NF-I site. I conclude that mouse mammary tumor virus
      employs the tandem octamer motifs of the viral promoter, recognized by the
      ubiquitous transcription factor Oct-1, for its basal transcriptional activity and
      the NF-I binding site, as previously shown, for glucocorticoid-stimulated
      transcription. A deletion mutant with only one octamer site showed a marked base
      level reduction at high copy number but little reduction at low copies of
      integrated plasmids. The observed transcription levels may depend both on the
      relative ratio of transcription factors to DNA templates and on the relative
      affinity of binding sites, as determined by oligonucleotide competition
      footprinting.

PMID- 8289801
TI  - DNA repair defects associated with chromosomal translocation breaksite regions.
AB  - Using an assay that measures the removal of UV-induced pyrimidine dimers in
      specific DNA sequences, we have found that the Pvt-1, immunoglobulin H-C alpha
      (IgH-C alpha), and IgL-kappa loci are poorly repaired in normal B lymphoblasts
      from plasmacytoma-susceptible BALB/cAnPt mice. Breaksites in these genes are
      associated with the chromosomal translocations that are found in > 95% of
      BALB/cAnPt plasmacytomas. In contrast to those from BALB/cAnPt mice, B
      lymphoblasts from plasmacytoma-resistant DBA/2N mice rapidly repair Pvt-1, IgH-C
      alpha, and IgL-kappa. Further, (BALB/cAnPt x DBA/2N)F1 hybrids, which are
      resistant to plasmacytoma development, carry an efficient (DBA/2N-like) repair
      phenotype. Analysis of allele-specific repair in the IgH-C alpha locus indicates
      that efficient repair is controlled by dominant, trans-acting factors. In the F1
      heterozygotes, these factors promote efficient repair of BALB/cAnPt IgH-C alpha
      gene sequences. The same sequences are poorly repaired in the BALB/cAnPt parental
      strain. Analysis of the strand specificity of repair indicates that both strand
      selective and nonselective forms of repair determine repair efficiency at the
      gene level in nonimmortalized murine B lymphoblasts.

PMID- 8289802
TI  - Positive regulatory elements (HF-1a and HF-1b) and a novel negative regulatory
      element (HF-3) mediate ventricular muscle-specific expression of myosin light
      chain 2-luciferase fusion genes in transgenic mice.
AB  - The cardiac myosin light-chain 2v (MLC-2v) gene has served as a model system to
      identify the pathways which restrict the expression of cardiac muscle genes to
      particular chambers of the heart during cardiogenesis. To identify the critical
      cis regulatory elements which mediate ventricular chamber-specific expression of
      the MLC-2v gene in the in vivo context, a series of transgenic mice which harbor
      mutations in putative MLC-2 cis regulatory elements in a 250-bp MLC-2-luciferase
      fusion gene which is expressed in a ventricular chamber-specific fashion in
      transgenic mice were generated. These studies demonstrate that both components of
      HF-1 (HF-1a and HF-1b/MEF-2) are required to maintain ventricular chamber
      specific expression and function as positive regulatory elements. Mutations in
      another conserved element (HF-2) are without statistically significant effect on
      ventricular chamber expression. Transgenics harboring mutations in the E-box site
      also displayed significant upregulation of reporter activity in the soleus,
      gastrocnemius, and uterus, with a borderline effect on expression in liver.
      Mutations in another conserved element (HF-3) result in a marked (> 75-fold)
      upregulation of the luciferase reporter activity in the soleus muscle of multiple
      independent or transgenic founders. Since the HF-3 mutations appeared to have
      only a marginal effect on luciferase reporter activity in liver tissue, HF-3
      appears to function as a novel negative regulatory element to primarily suppress
      expression in muscle tissues. Thus, a combination of positive (HF-1a/HF-1b) and
      negative (E-box and HF-3) regulatory elements appear to be required to maintain
      ventricular chamber-specific expression in the in vivo context.

PMID- 8289803
TI  - RFX1, a transactivator of hepatitis B virus enhancer I, belongs to a novel family
      of homodimeric and heterodimeric DNA-binding proteins.
AB  - RFX1 is a transactivator of human hepatitis B virus enhancer I. We show here that
      RFX1 belongs to a previously unidentified family of DNA-binding proteins of which
      we have cloned three members, RFX1, RFX2, and RFX3, from humans and mice. Members
      of the RFX family constitute the nuclear complexes that have been referred to
      previously as enhancer factor C, EP, methylation-dependent DNA-binding protein,
      or rpL30 alpha. RFX proteins share five strongly conserved regions which include
      the two domains required for DNA binding and dimerization. They have very similar
      DNA-binding specificities and heterodimerize both in vitro and in vivo. mRNA
      levels for all three genes, particularly RFX2, are elevated in testis. In other
      cell lines and tissues, RFX mRNA levels are variable, particularly for RFX2 and
      RFX3. RFX proteins share several novel features, including new DNA-binding and
      dimerization motifs and a peculiar dependence on methylated CpG dinucleotides at
      certain sites.

PMID- 8289804
TI  - HEN1 encodes a 20-kilodalton phosphoprotein that binds an extended E-box motif as
      a homodimer.
AB  - HEN1 and HEN2 encode neuron-specific polypeptides that contain the basic helix
      loop-helix (bHLH) motif, a protein dimerization and DNA-binding domain common to
      several known transcription factors. We now describe characteristics of the HEN1
      gene product that are consistent with its postulated role as a transcription
      factor that functions during development of the mammalian nervous system. Thus,
      transcription of the HEN1 gene is activated upon the induction of neural
      differentiation in PC12 cells by nerve growth factor. HEN1 encodes a 20-kDa
      polypeptide (pp20HEN1) that is phosphorylated exclusively at serine residues and
      forms dimeric bHLH complexes either by self-association or by heterologous
      interaction with the E2A gene products (E12 or E47). The resultant HEN1/HEN1
      homodimers and HEN1/E2A heterodimers bind DNA in a sequence-specific manner.
      Moreover, a binding site selection procedure revealed that HEN1-HEN1 homodimers
      preferentially recognize E-box motifs represented by an 18-bp consensus sequence
      (GGGNCG CAGCTGCGNCCC). The E-box half-site recognized by HEN1 polypeptides
      (GGGNCGCAG) is distinct from those of other known bHLH proteins, suggesting that
      HEN1 binds, an regulates the transcription of, a unique subset of target genes
      during neural development.

PMID- 8289805
TI  - Preferred sequences for DNA recognition by the TAL1 helix-loop-helix proteins.
AB  - Tumor-specific activation of the TAL1 gene is the most common genetic alteration
      seen in patients with T-cell acute lymphoblastic leukemia. The TAL1 gene products
      contain the basic helix-loop-helix (bHLH) domain, a protein dimerization and DNA
      binding motif common to several known transcription factors. A binding-site
      selection procedure has now been used to evaluate the DNA recognition properties
      of TAL1. These studies demonstrate that TAL1 polypeptides do not have intrinsic
      DNA-binding activity, presumably because of their inability to form bHLH
      homodimers. However, TAL1 readily interacts with any of the known class A bHLH
      proteins (E12, E47, E2-2, and HEB) to form heterodimers that bind DNA in a
      sequence-specific manner. The TAL1 heterodimers preferentially recognize a subset
      of E-box elements (CANNTG) that can be represented by the consensus sequence
      AACAGATGGT. This consensus is composed of half-sites for recognition by the
      participating class A bHLH polypeptide (AACAG) and the TAL1 polypeptide (ATGGT).
      TAL1 heterodimers with DNA-binding activity are readily detected in nuclear
      extracts of Jurkat, a leukemic cell line derived from a patient with T-cell acute
      lymphoblastic leukemia. Hence, TAL1 is likely to bind and regulate the
      transcription of a unique subset of subordinate target genes, some of which may
      mediate the malignant function of TAL1 during T-cell leukemogenesis.

PMID- 8289806
TI  - tRNA genes as transcriptional repressor elements.
AB  - Eukaryotic genomes frequently contain large numbers of repetitive RNA polymerase
      III (pol III) promoter elements interspersed between and within RNA pol II
      transcription units, and in several instances a regulatory relationship between
      the two types of promoter has been postulated. In the budding yeast Saccharomyces
      cerevisiae, tRNA genes are the only known interspersed pol III promoter
      containing repetitive elements, and we find that they strongly inhibit
      transcription from adjacent pol II promoters in vivo. This inhibition requires
      active transcription of the upstream tRNA gene but is independent of its
      orientation and appears not to involve simple steric blockage of the pol II
      upstream activator sites. Evidence is presented that different pol II promoters
      can be repressed by different tRNA genes placed upstream at varied distances in
      both orientations. To test whether this phenomenon functions in naturally
      occurring instances in which tRNA genes and pol II promoters are juxtaposed, we
      examined the sigma and Ty3 elements. This class of retrotransposons is always
      found integrated immediately upstream of different tRNA genes. Weakening tRNA
      gene transcription by means of a temperature-sensitive mutation in RNA pol III
      increases the pheromone-inducible expression of sigma and Ty3 elements up to 60
      fold.

PMID- 8289807
TI  - Homologous, homeologous, and illegitimate repair of double-strand breaks during
      transformation of a wild-type strain and a rad52 mutant strain of Saccharomyces
      cerevisiae.
AB  - Different modes of in vivo repair of double-strand breaks (DSBs) have been
      described for various organisms: the recombinational DSB repair (DSBR) mode, the
      single-strand annealing (SSA) mode, and end-to-end joining. To investigate these
      modes of DSB repair in Saccharomyces cerevisiae, we have examined the fate of in
      vitro linearized replicative plasmids during transformation with respect to
      several parameters. We found that (i) the efficiencies of both intramolecular and
      intermolecular linear plasmid DSB repair are homology dependent (according to the
      amount of DNA used during transformation [100 ng or less], recombination between
      similar but not identical [homeologous] P450s sequences sharing 73% identity is 2
      to 18-fold lower than recombination between identical sequences); (ii) the RAD52
      gene product is not essential for intramolecular recombination between homologous
      and homeologous direct repeats (as in the wild-type strain, recombination occurs
      with respect to the overall alignment of the parental sequences); (iii) in
      contrast, the RAD52 gene product is required for intermolecular interactions (the
      rare transformants which are obtained contain plasmids resulting from deletion
      forming intramolecular events involving little or no sequence homology); (iv)
      similarly, sequencing data revealed examples of intramolecular joining within the
      few terminal nucleotides of the transforming DNA upon transformation with a
      linear plasmid with no repeat in the wild-type strain. The recombinant junctions
      of the rare illegitimate events obtained with S. cerevisiae are very similar to
      those observed in the repair of DSB in mammalian cells. Together, these and
      previous results suggest the existence of alternative modes for DSB repair during
      transformation which differ in their efficiencies and in the structure of their
      products. We discuss the implications of these results with respect to the
      existence of alternative pathways and the role of the RAD52 gene product.

PMID- 8289808
TI  - Two different types of double-strand breaks in Saccharomyces cerevisiae are
      repaired by similar RAD52-independent, nonhomologous recombination events.
AB  - In haploid rad52 Saccharomyces cerevisiae strains unable to undergo homologous
      recombination, a chromosomal double-strand break (DSB) can be repaired by
      imprecise rejoining of the broken chromosome ends. We have used two different
      strategies to generate broken chromosomes: (i) a site-specific DSB generated at
      the MAT locus by HO endonuclease cutting or (ii) a random DSB generated by
      mechanical rupture during mitotic segregation of a conditionally dicentric
      chromosome. Broken chromosomes were repaired by deletions that were highly
      variable in size, all of which removed more sequences than was required either to
      prevent subsequent HO cleavage or to eliminate a functional centromere,
      respectively. The junction of the deletions frequently occurred where
      complementary strands from the flanking DNA could anneal to form 1 to 5 bp,
      although 12% (4 of 34) of the events appear to have occurred by blunt-end
      ligation. These types of deletions are very similar to the junctions observed in
      the repair of DSBs by mammalian cells (D. B. Roth and J. H. Wilson, Mol. Cell.
      Biol. 6:4295-4304, 1986). When a high level of HO endonuclease, expressed in all
      phases of the cell cycle, was used to create DSBs, we also recovered a large
      class of very small (2- or 3-bp) insertions in the HO cleavage site. These
      insertions appear to represent still another mechanism of DSB repair, apparently
      by annealing and filling in the overhanging 3' ends of the cleavage site. These
      types of events have also been well documented for vertebrate cells.

PMID- 8289809
TI  - Phenotypic rescue by a bovine transgene in a Cu/Zn superoxide dismutase-null
      mutant of Drosophila melanogaster.
AB  - Null mutants for Cu/Zn superoxide dismutase (CuZnSOD) in Drosophila melanogaster
      are male sterile, have a greatly reduced adult life span, and are hypersensitive
      to paraquat. We have introduced a synthetic bovine CuZnSOD transgene under the
      transcriptional control of the D. melanogaster 5C actin promoter into a CuZnSOD
      null mutant of D. melanogaster. This was carried out by P-element-mediated
      transformation of the Drosophila-bovine CuZnSOD transgene into a CuZnSOD+
      recipient strain followed by genetic crossing of the transgene into a strain
      carrying the CuZnSOD-null mutation, cSODn108. The resulting transformants express
      bovine CuZnSOD exclusively to about 30% of normal Drosophila CuZnSOD levels.
      Expression of the Drosophila-bovine CuZnSOD transgene in the CuZnSOD-null mutant
      rescues male fertility and resistance to paraquat to apparently normal levels.
      However, adult life span is restored to only 30% of normal, and resistance to
      hyperoxia is 90% of that found in control flies. This striking differential
      restoration of pleiotropic phenotypes could be the result of a threshhold of
      CuZnSOD expression necessary for normal male fertility and resistance to the
      toxicity of paraquat or hyperoxia which is lower than the threshold required to
      sustain a normal adult life span. Alternatively, the differential rescue of
      fertility, resistance to active oxygen, and life span might indicate different
      cell-specific transcriptional requirements for these functions which are normally
      provided by the control elements of the native CuZnSOD gene but are only partly
      compensated for by the transcriptional control elements of the actin 5C promoter.

PMID- 8289810
TI  - HLA class I heavy-chain gene promoter elements mediating synergy between tumor
      necrosis factor and interferons.
AB  - The cytokines tumor necrosis factor (TNF), beta interferon (IFN-beta), and IFN
      gamma increase major histocompatibility complex class I molecule expression. A
      greater than additive (i.e., synergistic) induction of class I heavy-chain mRNA
      is observed in HeLa cells treated with TNF in combination with either type of
      IFN. To define the cis-acting elements mediating cytokine synergy, the promoter
      of a human major histocompatibility complex class I heavy-chain gene (HLA-B7) was
      placed in front of a reporter gene and transfected into HeLa cells. Deletion
      analysis mapped the elements required for synergy to a 40-bp region containing a
      kappa B-like element, which is necessary for the response to TNF, and an
      interferon consensus sequence (ICS), which is necessary for the responses to
      IFNs. When the orientation of these elements was reversed or their normal 20-bp
      spacing was reduced by 5 or 10 bp, i.e., one half or one full turn of the DNA
      helix, essentially equivalent responses were obtained, suggesting that these
      parameters are not critical. In electromobility shift assays, a p50-containing NF
      kappa B nuclear factor from TNF-treated cells binds kappa B-containing probes,
      and ISGF-2 from IFN-gamma-treated cells binds ICS-containing probes. A probe
      containing both the kappa B and ICS elements (kappa B-ICS) forms a novel complex
      with nuclear factors isolated from cells treated with both TNF and IFN-gamma;
      this complex also forms when nuclear factors from individually cytokine-treated
      cells are mixed in vitro. The natural variant ICS found in HLA-A responds to IFN
      gamma and can mediate synergy with TNF. However, the variant kappa B found in HLA
      C does not respond to TNF, nor can it mediate synergy between TNF and IFN-gamma.
      These observations suggest that synergy between TNF and IFNs in the induction of
      HLA class I gene expression results from the sum of individual interactions of
      cytokine-activated enhancer-binding factors with the transcription initiation
      complex.

PMID- 8289811
TI  - The adenovirus E4-6/7 protein transactivates the E2 promoter by inducing
      dimerization of a heteromeric E2F complex.
AB  - Binding of the mammalian transcription factor E2F to the adenovirus E2a early
      promoter is modulated through interaction with the viral E4-6/7 protein. E4-6/7
      induces the cooperative and stable binding of E2F in vitro to two correctly
      spaced and inverted E2F binding sites in the E2a promoter (E2F induction) by
      physical interaction in the protein-DNA complex. The E2a promoter is
      transactivated in vivo by the E4-6/7 product. The C-terminal 70 amino acids of E4
      6/7 are necessary and sufficient for induction of E2F binding and for
      transactivation. To assess the mechanism(s) of E2a transactivation and the
      induction of cooperative E2F binding by the E4-6/7 protein, we have analyzed a
      series of point mutants in the functional C-terminal domain of E4-6/7. Two
      distinct segments of E4-6/7 are required for interaction with E2F. Additionally,
      and E4-6/7 mutant with a phenylalanine-to-proline substitution at amino acid 125
      (F-125-P) efficiently interacts with E2F but does not induce E2F binding to the
      E2a promoter and is defective for transactivation. Induction of E2F stable
      complex formation at the E2a promoter by the F-125-P mutant protein is restored
      by divalent E4-6/7-specific monoclonal antibodies, but not a monovalent Fab
      fragment, or by appending a heterologous dimerization domain to the N terminus of
      the mutant protein. These and other data support the involvement of E4-6/7
      dimerization in the induction of cooperative and stable E2F binding and
      transactivation of the E2a promoter. We present evidence that at least two
      cellular components are involved in E2F DNA binding activity and that both are
      required for E2F induction by the E4-6/7 product. The recently cloned E2F-related
      activities E2F-1 and DP-1 individually bind to an E2F binding site weakly, but
      when combined generate an activity that is indistinguishable from endogenous
      cellular E2F. Recombinant E2F-1, DP-1, and E4-6/7 are sufficient to form the
      induced E2F complex at the E2a promoter.

PMID- 8289812
TI  - Polypurine sequences within a downstream exon function as a splicing enhancer.
AB  - We have previously shown that a purine-rich sequence located within exon M2 of
      the mouse immunoglobulin mu gene functions as a splicing enhancer, as judged by
      its ability to stimulate splicing of a distant upstream intron. This sequence
      element has been designated ERS (exon recognition sequence). In this study, we
      investigated the stimulatory effects of various ERS-like sequences, using the in
      vitro splicing system with HeLa cell nuclear extracts. Here, we show that purine
      rich sequences of several natural exons that have previously been shown to be
      required for splicing function as a splicing enhancer like the ERS of the
      immunoglobulin mu gene. Moreover, even synthetic polypurine sequences had
      stimulatory effects on the upstream splicing. Evaluation of the data obtained
      from the analyses of both natural and synthetic purine-rich sequences shows that
      (i) alternating purine sequences can stimulate splicing, while poly(A) or poly(G)
      sequences cannot, and (ii) the presence of U residues within the polypurine
      sequence greatly reduces the level of stimulation. Competition experiments
      strongly suggest that the stimulatory effects of various purine-rich sequences
      are mediated by the same trans-acting factor(s). We conclude from these results
      that the purine-rich sequences that we examined in this study also represent
      examples of ERS. Thus, ERS is considered a general splicing element that is
      present in various exons and plays an important role in splice site selection.

PMID- 8289813
TI  - Human T-cell leukemia virus type I Tax associates with and is negatively
      regulated by the NF-kappa B2 p100 gene product: implications for viral latency.
AB  - Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of the adult T
      cell leukemia, an aggressive and often fatal malignancy of activated human CD4 T
      cells. HTLV-I encodes an essential 40-kDa protein termed Tax that not only
      transactivates the long terminal repeat of this retrovirus but also induces an
      array of cellular genes. Tax-mediated transformation of T cells likely involves
      the deregulated expression of various cellular genes that normally regulate
      lymphocyte growth produced by altered activity of various endogenous host
      transcription factors. In particular, Tax is capable of modulating the expression
      or activity of various host transcription factors, including members of the NF
      kappa B/Rel and CREB/ATF families, as well as the cellular factors HEB-1 and
      p67SRF. An additional distinguishing characteristic of HTLV-I infection is the
      profound state of viral latency that is present in circulating primary leukemic T
      cells. In this study, we demonstrate that HTLV-I Tax can physically associate
      with p100, the product of the Rel-related NF-kappa B2 gene, both in transfected
      cells and in HTLV-I-infected leukemic T-cell lines. Furthermore, the physical
      interaction of Tax with p100 leads to the inhibition of Tax-induced activation of
      the HTLV-I and human immunodeficiency virus type 1 long terminal repeats,
      reflecting p100-mediated cytoplasmic sequestration of the normally nuclearly
      expressed Tax protein. In contrast, a mutant of Tax that selectively fails to
      activate nuclear NF-kappa B expression does not associate with p100. Together,
      these results suggest that the cytoplasmic interplay of Tax and p100 may play an
      important role in the initiation and maintenance of HTLV-1 latency observed in
      adult T-cell leukemia.

PMID- 8289814
TI  - A novel cis-acting element controlling the rat CYP2D5 gene and requiring
      cooperativity between C/EBP beta and an Sp1 factor.
AB  - The rat CYP2D5 gene encodes a cytochrome P450 and is expressed in liver cells.
      Its expression commences a few days after birth, and maximal mRNA levels are
      achieved when animals reach puberty. Transfection and DNA binding studies were
      performed to investigate the mechanism controlling developmentally programmed,
      liver-specific expression of CYP2D5. Transfection studies using a series of
      CYP2D5 upstream DNA chloramphenicol acetyltransferase gene fusion constructs
      identified a segment of DNA between nucleotides -55 and -156 that conferred
      transcriptional activity in HepG2 cells. Activity was markedly increased by
      cotransfection with a vector expressing C/EBP beta but was unaffected by vectors
      producing other liver-enriched transcription factors (C/EBP alpha, HNF-1 alpha,
      and DBP). DNase I footprinting revealed a region protected by both HepG2 and
      liver cell nuclear extracts between nucleotides -83 and -112. This region
      displayed some sequence similarity to the Sp1 consensus sequence and was able to
      bind the Sp1 protein, as assessed by a gel mobility shift assay. The role of Sp1
      in CYP2D5 transcription was confirmed by trans activation of the 2D5-CAT
      construct in Drosophila melanogaster cells by using an Sp1 expression vector.
      C/EBP beta alone was unable to directly bind the -83 to -112 region of the
      promoter but was able to produce a ternary complex when combined with HepG2
      nuclear extracts or recombinant human Sp1. C/EBP alpha was unable to substitute
      for C/EBP beta in forming this ternary complex. A poor C/EBP binding site is
      present adjacent to the Sp1 site, and mutagenesis of this site abolished
      formation of the ternary complex with the CYP2D5 regulatory region. These result
      establish that two transcription factors can work in conjunction, possibly by
      protein-protein interaction, to activate the CYP2D5 gene.

PMID- 8289815
TI  - Purification of an oligo(dG).oligo(dC)-binding sea urchin nuclear protein, suGF1:
      a family of G-string factors involved in gene regulation during development.
AB  - Contiguous deoxyguanosine residues (G strings) have been implicated in regulation
      of gene expression in several organisms via the binding of G-string factors.
      Regulation of expression of the chicken adult beta-globin gene may involve the
      interplay between binding of an erythrocyte-specific G-string factor, BGP1, and
      the stability of a positioned nucleosome (C. D. Lewis, S. P. Clark, G.
      Felsenfeld, and H. Gould, Genes Dev. 2:863-873, 1988). We have purified a 59.5
      kDa nuclear protein (suGF1) from sea urchin embryos by DNA affinity
      chromatography. suGF1 has high binding affinity and specificity for
      oligo(dG).oligo(dC). The identity of the purified protein was confirmed by
      renaturation of sequence-specific DNA-binding activity from a sodium dodecyl
      sulfate-polyacrylamide gel slice and by Southwestern (DNA-protein) blotting.
      suGF1 binds in vitro to a G11 string present in the H1-H4 intergenic region of a
      sea urchin early histone gene battery. This suGF1 DNA recognition site occurs
      within a homopurine-homopyrimidine stretch previously shown to be incorporated
      into a positioned nucleosome core in vitro. DNase I footprinting shows that suGF1
      protects the same base pairs on the promoter of the chicken beta A-globin gene as
      does BGP1. We show that a G-string cis-regulatory element of a sea urchin cell
      lineage-specific gene LpS1 (M. Xiang, S.-Y. Lu, M. Musso, G. Karsenty, and W. H.
      Klein, Development 113:1345-1355, 1991) also represents a high-affinity
      recognition site for suGF1. suGF1 may be a member of a family of G-string factors
      involved in the regulation of expression of unrelated genes during development of
      a number of different organisms.

PMID- 8289816
TI  - suGF1 binds in the major groove of its oligo(dG).oligo(dC) recognition sequence
      and is excluded by a positioned nucleosome core.
AB  - We have elsewhere reported the purification of a poly(dG).poly(dC)-binding
      nuclear protein (suGF1) from sea urchin embryos (J. Hapgood and D. Patterton,
      Mol. Cell. Biol. 14:this issue, 1994). We proposed that suGF1 may be a member of
      a family of G-string factors involved in developmental gene regulation, possibly
      via alterations in chromatin structure. In this article, we characterize the
      binding of purified suGF1 to 11 contiguous Gs in the H1-H4 intergenic region of a
      sea urchin early histone gene battery in vitro. It is shown that suGF1-DNA
      binding is dependent on ionic strength and requires divalent cations. Purified
      suGF1 forms discrete protein-DNA multimers, consistent with suGF1-suGF1
      interactions. In a model for the suGF1-DNA complex derived from our footprinting
      and methylation interference data, suGF1 contacts the Gs in the major groove as
      well as one of the bordering phosphate backbones. The data are consistent with
      the direction of curvature of the DNA in the suGF1-DNA complex being the same as
      that preferred by the free DNA and exhibited by the DNA when bent around a
      positioned nucleosome core in vitro. However, on the basis of steric
      considerations, the binding of suGF1 and that of the histone octamer are
      predicted to be mutually exclusive. We show that suGF1 is indeed unable to bind
      to the G string when occupied by a histone octamer located in the major in vitro
      positioning frame in the H1-H4 intergenic region.

PMID- 8289817
TI  - High-resolution methylation analysis of the human hypoxanthine
      phosphoribosyltransferase gene 5' region on the active and inactive X
      chromosomes: correlation with binding sites for transcription factors.
AB  - DNA methylation within GC-rich promoters of constitutively expressed X-linked
      genes is correlated with transcriptional silencing on the inactive X chromosome
      in female mammals. For most X-linked genes, X chromosome inactivation results in
      transcriptionally active and inactive alleles occupying each female nucleus. To
      examine mechanisms responsible for maintaining this unique system of differential
      gene expression, we have analyzed the methylation of individual cytosine residues
      in the 5' CpG island of the human hypoxanthine phosphoribosyltransferase (HPRT)
      gene on the active and inactive X chromosomes. Methylation analysis of 142 CpG
      dinucleotides by genomic sequencing was carried out on purified DNA using the
      cytosine-specific Maxam and Gilbert DNA sequencing reaction in conjunction with
      ligation-mediated PCR. These studies demonstrate the 5' CpG islands of active and
      5-azacytidine-reactivated alleles are essentially unmethylated while the inactive
      allele is hypermethylated. The inactive allele is completely methylated at nearly
      all CpG dinucleotides except in a 68-bp region containing four adjacent GC boxes
      where most CpG dinucleotides are either unmethylated or partially methylated.
      Curiously, these GC boxes exhibit in vivo footprints only on the active X
      chromosome, not on the inactive X. The methylation pattern of the inactive HPRT
      gene is strikingly different from that reported for the inactive X-linked human
      phosphoglycerate kinase gene which exhibits methylation at all CpG sites in the
      5' CpG island. These results suggest that the position of methylated CpG
      dinucleotides, the density of methylated CpGs, the length of methylated regions,
      and/or chromatin structure associated with methylated DNA may have a role in
      repressing the activity of housekeeping promoters on the inactive X chromosome.
      The pattern of DNA methylation on the inactive human HPRT gene may also provide
      insight into the process of inactivating the gene early in female embryogenesis.

PMID- 8289818
TI  - Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony
      enhancing factor.
AB  - A novel gene coding for the pre-B-cell colony-enhancing factor (PBEF) has been
      isolated from a human peripheral blood lymphocyte cDNA library. The expression of
      this gene is induced by pokeweed mitogen and superinduced by cycloheximide. It is
      also induced in the T-lymphoblastoid cell line HUT 78 after phorbol ester
      (phorbol myristate acetate) treatment. The predominant mRNA for PBEF is
      approximately 2.4 kb long and codes for a 52-kDa secreted protein. The 3'
      untranslated region of the mRNA has multiple TATT motifs, usually found in
      cytokine and oncogene messages. The PBEF gene is mainly transcribed in human bone
      marrow, liver tissue, and muscle. We have expressed PBEF in COS 7 and PA317 cells
      and have tested the biological activities of the conditioned medium as well as
      the antibody-purified protein in different in vitro assays. PBEF itself had no
      activity but synergized the pre-B-cell colony formation activity of stem cell
      factor and interleukin 7. In the presence of PBEF, the number of pre-B-cell
      colonies was increased by at least 70% above the amount stimulated by stem cell
      factor plus interleukin 7. No effect of PBEF was found with cells of myeloid or
      erythroid lineages. These data define PBEF as a novel cytokine which acts on
      early B-lineage precursor cells.

PMID- 8289819
TI  - Nucleotide sequence of the yeast STE14 gene, which encodes farnesylcysteine
      carboxyl methyltransferase, and demonstration of its essential role in a-factor
      export.
AB  - Eukaryotic proteins initially synthesized with a C-terminal CAAX motif (C is Cys,
      A is aliphatic, and X can be one of several amino acids) undergo a series of
      modifications involving isoprenylation of the Cys residue, proteolysis of AAX,
      and alpha-carboxyl methyl esterification of the newly formed isoprenyl cysteine.
      We have previously demonstrated that STE14 encodes the enzyme which mediates
      carboxyl methylation of the Saccharomyces cerevisiae CAAX proteins a-factor,
      RAS1, and RAS2. Here we report the nucleotide sequence of STE14, which indicates
      that STE14 encodes a protein of 239 amino acids, predicted to contain multiple
      membrane-spanning segments. Mapping data indicate that STE14 resides on
      chromosome IV, tightly linked to ADE8. By analysis of ste14 null alleles, we
      demonstrated that MATa ste14 mutants are unable to mate but are viable and
      exhibit no apparent growth defects. Additional analysis of ste14 ras 1 and ste14
      ras2 double mutants, which grow normally, reinforces our previous conclusion that
      RAS function is not significantly influenced by its methylation status. We
      examine a-factor biogenesis in a ste14 null mutant by metabolic labeling and
      immunoprecipitation and demonstrate that although proteolytic processing and
      membrane localization of a-factor are normal, the ste14 null mutant exhibits a
      profound block in a-factor export. This observation suggests that the methyl
      group is likely to be a critical recognition determinant for the a-factor
      transporter, STE6, thus providing insight into the substrate specificity of STE6
      and also supporting the hypothesis that carboxyl methylation can have a dramatic
      impact on protein-protein interactions.

PMID- 8289820
TI  - Regulation and targeting of recombination in extrachromosomal substrates carrying
      immunoglobulin switch region sequences.
AB  - We have used extrachromosomal substrates carrying immunoglobulin heavy-chain S mu
      and S gamma 3 switch region sequences to study activation and targeting of
      recombination by a transcriptional enhancer element. Substrates are transiently
      introduced into activated primary murine B cells, in which recombination
      involving S-region sequences deletes a conditionally lethal marker, and
      recombination is measured by transformation of Escherichia coli in the second
      step of the assay. Previously we found that as many as 25% of replicated
      substrates recombined during 40-h transfection of lipopolysaccharide (LPS)
      stimulated primary cells and that efficient recombination was dependent on the
      presence of S-region sequences as well as a transcriptional activator region in
      the constructs (H. Leung and N. Maizels, Proc. Natl. Acad. Sci. USA 89:4154-4158,
      1992). Here we show that recombination of the switch substrates is threefold more
      efficient in LPS-cultured primary B cells than in the T-cell line EL4; the
      activities responsible for switch substrate recombination thus appear to be more
      abundant or more active in cells which can carry out chromosomal switch
      recombination. We test the role of the transcriptional activator region and show
      that the immunoglobulin heavy-chain intron enhancer (E mu) alone stimulates
      recombination as well as E mu combined with a heavy-chain promoter and that
      mutations that diminish enhancer-dependent transcription 500-fold diminish
      recombinational activation less than 2-fold. These observations suggest that the
      enhancer stimulates recombination by a mechanism that does not depend on
      transcript production or that is insensitive to the level of transcript
      production over a very broad range. Furthermore, we find that E mu stimulates
      recombination when located either upstream or downstream of S mu but that the
      position of the recombinational activator does affect the targeting of
      recombination junctions, suggesting that the relatively imprecise targeting of
      switch junctions in vivo may reflect the availability of many potential activator
      sites within each switch region.

PMID- 8289821
TI  - The carboxy-terminal region of mammalian HSP90 is required for its dimerization
      and function in vivo.
AB  - The majority of mouse HSP90 exists as alpha-alpha and beta-beta homodimers.
      Truncation of the 15-kDa carboxy-terminal region of mouse HSP90 by digestion with
      the Ca(2+)-dependent protease m-calpain caused dissociation of the dimer. When
      expressed in a reticulocyte lysate, the full-length human HSP90 alpha formed a
      dimeric form. A plasmid harboring human HSP90 alpha cDNA was constructed so that
      the carboxy-terminal 49 amino acid residues were removed when translated in
      vitro. This carboxy-terminally truncated human HSP90 alpha was found to exist as
      a monomer. In contrast, loss of the 118 amino acid residues from the amino
      terminus of human HSP90 alpha did not affect its in vitro dimerization.
      Introduction of an expression plasmid harboring the full-length human HSP90 alpha
      complements the lethality caused by the double mutations of two HSP90-related
      genes, hsp82 and hsc82, in a haploid strain of Saccharomyces cerevisiae. The
      carboxy-terminally truncated human HSP90 alpha neither formed dimers in yeast
      cells nor rescued the lethal double mutant.

PMID- 8289822
TI  - Nature and distribution of chromosomal intertwinings in Saccharomyces cerevisiae.
AB  - To elucidate yeast chromosome structure and behavior, we examined the breakage of
      entangled chromosomes in DNA topoisomerase II mutants by hybridization to
      chromosomal DNA resolved by pulsed-field gel electrophoresis. Our study reveals
      that large and small chromosomes differ in the nature and distribution of their
      intertwinings. Probes to large chromosomes (450 kb or larger) detect chromosome
      breakage, but probes to small chromosomes (380 kb or smaller) reveal no breakage
      products. Examination of chromosomes with one small arm and one large arm
      suggests that the two arms behave independently. The acrocentric chromosome XIV
      breaks only on the long arm, and its preferred region of breakage is
      approximately 200 kb from the centromere. When the centromere of chromosome XIV
      is relocated, the preferred region of breakage shifts accordingly. These results
      suggest that large chromosomes break because they have long arms and small
      chromosomes do not break because they have small arms. Indeed, a small
      metacentric chromosome can be made to break if it is rearranged to form a
      telocentric chromosome with one long arm or a ring with an "infinitely" long arm.
      These results suggest a model of chromosomal intertwining in which the length of
      the chromosome arm prevents intertwinings from passively resolving off the end of
      the arm during chromosome segregation.

PMID- 8289823
TI  - Human cancer cell lines express a negative transcriptional regulator of the
      interferon regulatory factor family of DNA binding proteins.
AB  - Members of the interferon regulatory factor (IRF) family of DNA binding
      transcription factors have roles in growth regulation, antiviral responses, and
      transcriptional induction of interferon (IFN)-activated early response genes. The
      IRF family member ISGF3 gamma is the DNA binding component of IFN-stimulated gene
      factor 3 (ISGF3), a multicomponent complex responsible for the stimulation of IFN
      alpha-responsive genes. IFN-alpha-stimulated formation of ISGF3 and subsequent
      gene expression can be inhibited by phorbol esters or expression of the
      adenovirus E1A protein. We have investigated IFN signaling in human malignant
      tumor cell lines of the lung, colon, ovary, cervix, and hematopoietic organs and
      found some of these cells to be defective for IFN-alpha-induced formation of
      ISGF3. In many cases, an inhibitory activity termed transcriptional knockout
      (TKO) correlated with nonresponsiveness. TKO purified from a human papillomavirus
      negative cervical carcinoma cell line has a molecular size of 19 kDa. The
      purified protein interacted with the ISGF3 gamma component of ISGF3, preventing
      binding of ISGF3 to DNA. Purified TKO displaced ISGF3 from its DNA binding site
      in vitro and prevented ISGF3 gamma, IRF-1, and IRF-2 from interacting with the
      IFN-stimulated response element. Partially purified TKO can also directly
      interact with ISGF3 gamma in the absence of DNA. This protein may be involved
      with the development of malignancies and the inability of IFN to exert its
      antiproliferative and antiviral effects.

PMID- 8289825
TI  - Analysis of an origin of DNA amplification in Sciara coprophila by a novel three
      dimensional gel method.
AB  - The replication origin region for DNA amplification in Sciara coprophila DNA puff
      II/9A was analyzed with a novel three-dimensional (3D) gel method. Our 3D gel
      method involves running a neutral/neutral 2D gel and then cutting out vertical
      gel slices from the area containing replication intermediates, rotating these
      slices 90 degrees to form the third dimension, and running an alkaline gel for
      each of the slices. Therefore, replication intermediates are separated into forks
      and bubbles and then are resolved into parental and nascent strands. We used this
      technique to determine the size of forks and bubbles and to confirm the location
      of the major initiation region previously mapped by 2D gels to a 1-kb region.
      Furthermore, our 3D gel analyses suggest that only one initiation event in the
      origin region occurs on a single DNA molecule and that the fork arc in the
      composite fork-plus-bubble pattern in neutral/neutral 2D gels does not result
      from broken bubbles.

PMID- 8289824
TI  - The Drosophila l(2)35Ba/nocA gene encodes a putative Zn finger protein involved
      in the development of the embryonic brain and the adult ocellar structures.
AB  - The Drosophila l(2)35Ba/nocA gene is involved in the development of the adult
      ocelli and the embryonic head. Mutations in this gene lead to at least two
      distinct phenotypes. Several larva lethal l(2)35Ba alleles cause both hypertrophy
      and mislocation of the embryonic supraesophageal ganglion (brain) to the dorsal
      surface of the embryo. A second class of mutant alleles (nocA) is homozygous
      viable, but the surviving adults either lack or have greatly reduced ocelli and
      associated bristles. The l(2)35Ba/nocA gene encodes an approximately 3.0-kb
      transcript doublet; all l(2)35Ba alleles which have been physically mapped delete
      or disrupt the transcribed region, whereas all of the viable nocA alleles are
      caused by gross chromosomal aberrations with breakpoints near the 3'-flanking
      region of the gene. Several nocA breakpoint alleles downregulate the level of
      l(2)35Ba/nocA transcripts in adults, and their defective ocellar phenotype also
      fails to be complemented by the lethal alleles, implying that l(2)35Ba and nocA
      are different phenotypic manifestations of mutations in the same gene. In the
      l(2)35Ba mutant embryos, cells from the procephalic lobe which normally migrate
      over and overlie the supraesophageal ganglion during head involution can become
      incorporated into the supraesophageal ganglion; many of these misplaced cells,
      which normally form the frontal sac, also adopt a neuronal fate. Sequence
      analysis of two full-length l(2)35Ba/nocA cDNAs with distinct polyadenylation
      sites shows that they encode the same deduced protein of 537 amino acids with a
      serine- and threonine-rich N-terminal region, two putative zinc finger motifs
      near the carboxyl terminus, and several alanine-rich domains. Consistent with the
      observed embryonic phenotype, l(2)35Ba/nocA shows a complex embryonic expression
      pattern which includes the procephalic lobe.

PMID- 8289826
TI  - Glucose-induced transcription of the insulin gene is mediated by factors required
      for beta-cell-type-specific expression.
AB  - The insulin gene is expressed exclusively in pancreatic islet beta cells. The
      principal regulator of insulin gene transcription in the islet is the
      concentration of circulating glucose. Previous studies have demonstrated that
      transcription is regulated by the binding of trans-acting factors to specific cis
      acting sequences within the 5'-flanking region of the insulin gene. To identify
      the cis-acting control elements within the rat insulin II gene that are
      responsible for regulating glucose-stimulated expression in the beta cell, we
      analyzed the effect of glucose on the in vivo expression of a series of
      transfected 5'-flanking deletion mutant constructs. We demonstrate that glucose
      induced transcription of the rat insulin II gene is mediated by sequences located
      between -126 and -91 bp relative to the transcription start site. This region
      contains two cis-acting elements that are essential for directing pancreatic beta
      cell-type-specific expression of the rat insulin II gene, the insulin control
      element (ICE; -100 to -91 bp) and RIPE3b1 (-115 to -107 bp). The gel mobility
      shift assay was used to determine whether the formation of the ICE- and RIPE3b1
      specific factor-DNA element complexes were affected in glucose-treated beta-cell
      extracts. We found that RIPE3b1 binding activity was selectively induced by about
      eightfold. In contrast, binding to other insulin cis-acting element sequences
      like the ICE and RIPE3a2 (-108 to -99 bp) were unaffected by these conditions.
      The RIPE3b1 binding complex was shown to be distinct from the glucose-inducible
      factor that binds to an element located between -227 to -206 bp of the human and
      rat insulin I genes (D. Melloul, Y. Ben-Neriah, and E. Cerasi, Proc. Natl. Acad.
      Sci. USA 90:3865-3869, 1993). We have also shown that mannose, a sugar that can
      be metabolized by the beta cell, mimics the effects of glucose in the in vivo
      transfection assays and the in vitro RIPE3b1 binding assays. These results
      suggested that the RIPE3b1 transcription factor is a primary regulator of glucose
      mediated transcription of the insulin gene. However, we found that mutations in
      either the ICE or the RIPE3b1 element reduced glucose-responsive expression from
      transfected 5'-flanking rat insulin II gene constructs. We therefore conclude
      that glucose-regulated transcription of the insulin gene is mediated by cis
      acting elements required for beta-cell-type-specific expression.

PMID- 8289827
TI  - A simple and efficient procedure for generating stable expression libraries by
      cDNA cloning in a retroviral vector.
AB  - cDNA expression cloning is a powerful method for the rescue and identification of
      genes that are able to confer a readily identifiable phenotype on specific cell
      types. Retroviral vectors provide several advantages over DNA-mediated gene
      transfer for the introduction of expression libraries into eukaryotic cells since
      they can be used to express genes in a wide range of cell types, including those
      that form important experimental systems such as the hemopoietic system. We
      describe here a straightforward and efficient method for generating expression
      libraries by using a murine retroviral vector. Essentially, the method involves
      the directional cloning of cDNA into the retroviral vector and the generation of
      pools of stable ecotropic virus producing cells from this DNA. The cells so
      derived constitute the library, and the virus they yield is used to infect
      appropriate target cells for subsequent functional screening. We have
      demonstrated the feasibility of this procedure by constructing several large
      retroviral libraries (10(5) to 10(6) individual clones) and then using one of
      these libraries to isolate cDNAs for interleukin-3 and granulocyte-macrophage
      colony-stimulating factor on the basis of the ability of these factors to confer
      autonomous growth on the factor-dependent hemopoietic cell line FDC-P1. Moreover,
      the frequency at which these factor-independent clones were isolated approximated
      the frequency at which they were represented in the original plasmid library.
      These results suggest that expression cloning with retroviruses is a practical
      and efficient procedure and should be a valuable method for the isolation of
      important regulatory genes.

PMID- 8289828
TI  - Mechanisms of overlap formation in nonhomologous DNA end joining.
AB  - Rejoining of nonhomologous DNA termini plays a central role in processes of
      illegitimate recombination. In Xenopus egg extracts, DNA ends with
      noncomplementary 4-nucleotide antiparallel single-strand protrusions are assumed
      to be joined by formation of short mismatched overlap intermediates. The extents
      of these overlaps may be set by single fortuitously matching base pairs and
      determine the patterns of subsequent gap filling and nick ligation. Under
      conditions of alternative overlap settings, rules for the most probable joining
      pathway and the effects of mismatches on junction formation were analyzed. We
      show that in certain cases, fill-in and ligation converting overlap intermediates
      into covalently closed junctions may proceed in the presence of unrepaired
      mismatches, whereas in other cases, completion of junction formation is preceded
      by removal of mismatches. Results are discussed in relation with "alignment"
      proteins postulated to structurally support overlap heteroduplexes during
      junction formation.

PMID- 8289829
TI  - The mutant type 1 protein phosphatase encoded by glc7-1 from Saccharomyces
      cerevisiae fails to interact productively with the GAC1-encoded regulatory
      subunit.
AB  - Loss-of-function gac1 mutants of Saccharomyces cerevisiae fail to accumulate
      normal levels of glycogen because of low glycogen synthase activity. Increased
      dosage of GAC1 results in increased activity of glycogen synthase and a
      corresponding hyperaccumulation of glycogen. The glycogen accumulation phenotype
      of gac1 is similar to that of glc7-1, a type 1 protein phosphatase mutant. We
      have partially characterized the GAC1 gene product (Gac1p) and show that levels
      of Gac1p increase during growth with the same kinetics as glycogen accumulation.
      Gac1p is phosphorylated in vivo and is hyperphosphorylated in a glc7-1 mutant.
      Gac1p and the type 1 protein phosphatase directly interact in vitro, as assayed
      by coimmunoprecipitation, and in vivo, as determined by the dihybrid assay
      described elsewhere (S. Fields and O.-k. Song, Nature [London] 340:245-246,
      1989). The interaction between Gac1p and the glc7-1-encoded form of the type 1
      protein phosphatase is defective, as assayed by either immunoprecipitation or the
      dihybrid assay. Increased dosage of GAC1 partially suppresses the glycogen defect
      of glc7-1. Collectively, our data support the hypotheses that GAC1 encodes a
      regulatory subunit of type 1 protein phosphatase and that the glycogen
      accumulation defect of glc7-1 is due at least in part to the inability of the
      mutant phosphatase to interact with its regulatory subunit.

PMID- 8289830
TI  - Activation of Ras in vitro and in intact fibroblasts by the Vav guanine
      nucleotide exchange protein.
AB  - We recently identified Vav, the product of the vav proto-oncogene, as a guanine
      nucleotide exchange factor (GEF) for Ras. Vav is enzymatically activated by
      lymphocyte antigen receptor-coupled protein tyrosine kinases or independently by
      diglycerides. To further evaluate the physiological role of Vav, we assessed its
      GDP-GTP exchange activity against several Ras-related proteins in vitro and
      determined whether Vav activation in transfected NIH 3T3 fibroblasts correlates
      with the activity status of Ras and mitogen-activated protein (MAP) kinases. In
      vitro translated purified Vav activated by phorbol myristate acetate (PMA) or
      phosphorylation with recombinant p56lck displayed GEF activity against Ras but
      not against recombinant RacI, RacII, Ral, or RhoA proteins. Expression of vav or
      proto-vav in stably transfected NIH 3T3 cells led to a approximately 10-fold
      increase in basal or PMA-stimulated Ras exchange activity, respectively, in total
      cell lysates and Vav immunoprecipitates. Elevated GEF activity was paralleled in
      each case by a significant increase in the proportion of active, GTP-bound Ras.
      PMA had a minimal effect on the low Ras. GTP level in untransfected control
      fibroblasts but increased it from 20 to 37% in proto-vav-transfected cells. vav
      transfected cells displayed a constitutively elevated Ras. GTP level (35%), which
      was not increased further by PMA treatment. MAP kinases, known downstream
      intermediates in Ras-dependent signaling pathways, similarly exhibited increased
      basal or PMA-stimulated activity in Vav-expressing cells by comparison with
      normal NIH 3T3 cells. These results demonstrate a physiologic interaction between
      Vav and its target, Ras, leading to MAP kinase activation.

PMID- 8289831
TI  - A unique palindromic element mediates gamma interferon induction of mig gene
      expression.
AB  - To define the molecular mechanisms involved in the action of gamma interferon
      (IFN-gamma), we have analyzed the transcriptional regulation of the mig (monokine
      induced by gamma interferon) gene, a member of the platelet factor 4-interleukin
      8 cytokine family that is expressed in murine macrophages specifically in
      response to IFN-gamma. Analysis of mig/CAT chimeric constructs transiently
      transfected into the RAW 264.7 mouse monocytic cell line revealed a unique IFN
      gamma-responsive element (gamma RE-1). The sequence of this cis regulatory
      element defined by deletion analysis contains an imperfect inverted repeat
      extending 27 bp. Examination of mig/CAT constructs with mutations in gamma RE-1
      revealed that the palindromic positions in the element were essential for
      activity. Consistent with its function as an enhancer, a single copy of gamma RE
      1 conferred IFN-gamma inducibility to a heterologous (herpes simplex virus
      thymidine kinase) promoter. Exonuclease III protection assays demonstrated
      symmetrical protection of a mig promoter fragment centered about the gamma RE-1
      palindromic sequence. Using the gel electrophoretic mobility shift assay, we
      identified a factor (gamma RF-1) present in nuclear extracts prepared from IFN
      gamma-stimulated RAW 264.7 cells which binds to gamma RE-1. The activation of
      gamma RF-1 occurred rapidly (within 1 min) in response to IFN-gamma and was
      independent of protein synthesis. Similar to the expression of mig mRNA, the
      formation of gamma RF-1 was selectively induced by IFN-gamma and not IFN-alpha.
      The regulation of gene expression through gamma RF-1 and gamma RE-1 may explain
      the preferential activation of a subset of interferon-inducible genes by IFN
      gamma.

PMID- 8289832
TI  - The B subunit of the DNA polymerase alpha-primase complex in Saccharomyces
      cerevisiae executes an essential function at the initial stage of DNA
      replication.
AB  - The four-subunit DNA polymerase alpha-primase complex is unique in its ability to
      synthesize DNA chains de novo, and some in vitro data suggest its involvement in
      initiation and elongation of chromosomal DNA replication, although direct in vivo
      evidence for a role in the initiation reaction is still lacking. The function of
      the B subunit of the complex is unknown, but the Saccharomyces cerevisiae POL12
      gene, which encodes this protein, is essential for cell viability. We have
      produced different pol12 alleles by in vitro mutagenesis of the cloned gene. The
      in vivo analysis of our 18 pol12 alleles indicates that the conserved carboxy
      terminal two-thirds of the protein contains regions that are essential for cell
      viability, while the more divergent NH2-terminal portion is partially
      dispensable. The characterization of the temperature-sensitive pol12-T9 mutant
      allele demonstrates that the B subunit is required for in vivo DNA synthesis and
      correct progression through S phase. Moreover, reciprocal shift experiments
      indicate that the POL12 gene product plays an essential role at the early stage
      of chromosomal DNA replication, before the hydroxyurea-sensitive step. A model
      for the role of the B subunit in initiation of DNA replication at an origin is
      presented.

PMID- 8289833
TI  - Multiple silencer elements are involved in regulating the chicken vimentin gene.
AB  - Vimentin, a member of the intermediate filament protein family, exhibits tissue-
      as well as development-specific expression. Transcription factors that are
      involved in expression of the chicken vimentin gene have been described and
      include a cis-acting silencer element (SE3) that is involved in the down
      regulation of this gene (F. X. Farrell, C. M. Sax, and Z. E. Zehner, Mol. Cell.
      Biol. 10:2349-2358, 1990). In this study, we report the identification of two
      additional silencer elements (SE1 and SE2). We show by transfection analysis that
      all three silencer elements are functionally active and that optimal silencing
      occurs when multiple (at least two) silencer elements are present. In addition,
      the previously identified SE3 can be divided into three subregions, each of which
      is moderately active alone. By gel mobility shift assays, all three silencer
      elements plus SE3 subregions bind a protein which by Southwestern (DNA-protein)
      blot analysis is identical in molecular mass (approximately 95 kDa). DNase I
      footprinting experiments indicate that this protein binds to purine-rich sites.
      Therefore, multiple elements appear to be involved in the negative regulation of
      the chicken vimentin gene, which may be important in the regulation of other
      genes as well.

PMID- 8289834
TI  - Two distinct transmembrane serine/threonine kinases from Drosophila melanogaster
      form an activin receptor complex.
AB  - A transmembrane protein serine/threonine kinase, Atr-I, that is structurally
      related to receptors for members of the transforming growth factor-beta (TGF
      beta) family has been cloned from Drosophila melanogaster. The spacing of
      extracellular cysteines and the cytoplasmic domain of Atr-I resemble most closely
      those of the recently described mammalian type I receptors for TGF-beta and
      activin. When expressed alone in test cells, Atr-I is unable to bind TGF-beta,
      activin, or bone morphogenetic protein 2. However, Atr-I binds activin
      efficiently when coexpressed with the distantly related Drosophila activin
      receptor Atr-II, with which it forms a heteromeric complex. Atr-I can also bind
      activin in concert with mammalian activin type II receptors. Two alternative
      forms of Atr-I have been identified that differ in an ectodomain region
      encompassing the cysteine box motif characteristic of receptors in this family.
      Comparison of Atr-I with other type I receptors reveals the presence of a
      characteristic 30-amino-acid domain immediately upstream of the kinase region in
      all these receptors. This domain, of unknown function, contains a repeated Gly
      Ser sequence and is therefore referred to as the GS domain. Maternal Atr-I
      transcripts are abundant in the oocyte and widespread during embryo development
      and in the imaginal discs of the larva. The structural properties, binding
      specificity, and dependence on type II receptors define Atr-I as an activin type
      I receptor from D. melanogaster. These results indicate that the heteromeric
      kinase structure is a general feature of this receptor family.

PMID- 8289835
TI  - Two different sequence elements within exon 4 are necessary for calcitonin
      specific splicing of the human calcitonin/calcitonin gene-related peptide I pre
      mRNA.
AB  - The calcitonin (CT)/calcitonin gene-related peptide I (CGRP-I) gene (CALC-I gene)
      is subject to alternative tissue-specific processing of its primary transcript.
      CT mRNA is the predominant mRNA produced in thyroid C cells, whereas CT gene
      related peptide I mRNA is the main product in neurons of the central and
      peripheral nervous systems. The CT-specific exon 4 is surrounded by weak
      processing sites. In this study we have investigated whether exon 4 sequences are
      involved in the tissue-specific selection of the exon 4 splice acceptor site. The
      results indicate that two separate elements, termed A and B, in the 5' part of
      exon 4 are required for production of CT-specific RNA. These sequences are
      located between nucleotides 67 and 88 (A) and nucleotides 117 and 146 (B)
      relative to the 5' end of exon 4. Variation of the distance between these
      sequence elements and the 3' splice site of exon 4 does not change the processing
      choice. These sequence elements are functionally equivalent. CT-specific splicing
      requires the presence of both sequence A and B or duplicates of either sequence
      element in exon 4. The effect of these sequences on the RNA processing choice is
      overruled by mutation of the CT-specific uridine branch acceptor nucleotide into
      a commonly preferred adenosine residue.

PMID- 8289838
TI  - [Restriction system--type II modification in Enterobacter cloacae strains].
AB  - Various clinical strains of Enterobacter cloacae have been examined for the
      presence of site-specific endonuclease activities. Restriction endonucleases of
      class II have been isolated from six strains. Recognition sequences for all of
      these endonucleases were determined and the cleavage sites were identified for
      two of them. The enzymes prove to be isoschizomers of EcoRII and PstI.
      Restriction endonucleases Ecl2zI and Ecl37kI recognise the nucleotide sequences
      CTGA/G and are true isoschizomers of PstI. The genes for Ecl54kI and Ecl57kI
      restriction-modification systems (isoschizomers of EcoRII) were found to be
      located on the IncN group plasmids, whereas the genes for Ecl2zI and Ecl99kI seem
      to be located on the chromosomes of host cells.

PMID- 8289836
TI  - Restoration of telomeres in human papillomavirus-immortalized human anogenital
      epithelial cells.
AB  - Loss of telomeres has been hypothesized to be important in cellular senescence
      and may play a role in carcinogenesis. In this study, we have measured telomere
      length in association with the immortalization and transformation of human
      cervical and foreskin epithelial cells by the human papillomavirus type 16 or 18
      E6 and E7 open reading frames. By using a telomeric TTAGGG repeat probe, it was
      shown that the telomeres of precrisis normal and E6-, E7-, and E6/E7-expressing
      cells gradually shortened with passaging (30 to 100 bp per population doubling).
      Cells that expressed both E6 and E7 went through a crisis period and gave rise to
      immortalized lines. In contrast to precrisis cells, E6/E7-immortalized cells
      generally showed an increase in telomere length as they were passaged in culture,
      with some later passage lines having telomeres that were similar to or longer
      than the earliest-passage precrisis cells examined. No consistent association
      could be made between telomere length and tumorigenicity of cells in nude mice.
      However, of the three cell lines that grew in vivo, two had long telomeres, thus
      arguing against the hypothesis that cancer cells favor shortened telomeres. Our
      results indicate that arrest of telomere shortening may be important in human
      papillomavirus-associated immortalization and that restoration of telomere length
      may be advantageous to cells with regard to their ability to proliferate.

PMID- 8289837
TI  - Role of the histone amino termini in facilitated binding of a transcription
      factor, GAL4-AH, to nucleosome cores.
AB  - Facilitated, "cooperative" binding of GAL4-AH to nucleosomal DNA occurred in
      response to inhibition from the core histone amino termini. The binding of GAL4
      AH (which contains the DNA-binding and dimerization domains of GAL4) to
      nucleosome cores containing multiple binding sites initiated at the end of a
      nucleosome core and proceeded in a cooperative manner until all sites were
      occupied. However, following tryptic removal of the core histone amino termini,
      GAL4-AH binding appeared to be noncooperative, similar to binding naked DNA.
      Binding of GAL4-AH to nucleosomes bearing a single GAL4 site at different
      positions indicated that inhibition of GAL4 binding was largely mediated by the
      histone amino termini and primarily occurred at sites well within the core and
      not near the end. When the histone amino termini were intact, binding of GAL4-AH
      to sites near the center of a nucleosome core was greatly enhanced by the
      presence of additional GAL4 dimers bound to more-accessible positions. These data
      illustrate that the binding of a factor to more-accessible sites, near the end of
      a nucleosome, allows facilitated binding of additional factors to the center of
      the nucleosome, thereby overcoming repression from the core histone amino
      termini. This mechanism may contribute to the binding of multiple factors to
      complex promoter and enhancer elements in cellular chromatin.

PMID- 8289839
TI  - [Regulation of enzymes of the first and last stage of lysine biosynthesis in
      Streptococcus bovis and Enterococcus faecium].
AB  - Regulation of aspartate kinase and diaminopimelate decarboxylase activities in
      Streptococcus bovis and Enterococcus faecium cell-free extracts was studied. The
      levels of synthesis of aspartate kinase and diaminopimelate decarboxylase in both
      microorganisms are growth-dependent. The synthesis of these enzymes is depressed
      by lysine, but the activity of aspartate kinase is induced by addition of this
      amino acid and threonine to the reaction system. Meso-diaminopimelate
      dehydrogenase activity was not found in the extracts of Streptococcus bovis and
      Enterococcus faecium. The data excludes the possibility of lysine formation via
      six enzyme reactions.

PMID- 8289840
TI  - [Design of recombinant DNA intended for insertional mutagenesis of bacteria].
AB  - The recombinant plasmid pKC47M has been constructed on the base of a mini-Mu
      phage and the replicon of plasmid pBR328. The plasmid was constructed for in vivo
      insertional mutagenesis in bacteria. Use of the plasmid in vivo alleviates the
      possibility of secondary transposition of the inserted sequences and enrichment
      of multiple-site mutations. Efficient mutagenesis caused by plasmid pKC47M was
      tested by induction auxotrophic mutations in Escherichia coli, Yersinia
      enterocolitica, Yersinia pseudotuberculosis.

PMID- 8289841
TI  - [Selective photoimmunoinactivation of influenza virus].
AB  - Antibodies to influenza virus were conjugated with hematoporphyrin. The
      conjugates were verified by the peak point identity in protein absorption (lambda
      280 nm) of elution profiles and by the porphyrin-specific fluorescence. The
      antibody conjugates have been shown to preserve the specific antigenic activity
      tested by enzyme immunoassay. The conjugated hematoporphyrin nuclei have also
      preserved the photochemical activity since the antibody conjugates lose their
      native properties being exposed to visible light. In the neutralization test in
      the dark the conjugates of specific antibodies with hematoporphyrin decrease the
      viral cultures infectivity to the same extent as nonconjugated antibodies. This
      fact verifies antibodies stability in the conjugates. The infectivity of viral
      cultures exposed to visible light after neutralization test was further decreased
      by several orders. The data suggest undoubtedly perspective use of this method in
      viral infections control.

PMID- 8289842
TI  - [The role of pyrimidines in the biosynthesis of the fluorescing pigment pyoverdin
      Pm in Pseudomonas putida M].
AB  - Dihydroorotate was shown to be a predecessor of deoxyquinoline nucleus of a
      fluorescing enzyme pyoverdin Pm in Pseudomonas putida M. The data was obtained in
      experiments with a set of Pyr- mutants with different steps of pyrimidine
      synthesis blocked. A scheme for deoxyquinoline nucleus of the enzyme including
      dihydroorotate participation is proposed.

PMID- 8289843
TI  - [Expression of the vif gene of human immunodeficiency virus type 1 in Escherichia
      coli and study of the immunoreactivity of the vif protein].
AB  - Full-sized gen vif of human immunodeficiency virus has been synthesized and
      cloned into plasmid pGEX-2T. Vif-gene expression was found in Escherichia coli
      cells resulting in production of a hybrid GST-protein. The recombinant protein
      studied by the immunoblotting technique reacted with 8 of 22 probes of human HIV
      positive sera. The recombinant protein is specifically cut by thrombin in two
      proteins corresponding to GST and VIF-proteins in molecular mass.

PMID- 8289844
TI  - Comparative studies of the interaction between lectins and Leishmania in
      agglutination tests and enzyme-linked lectin-biotin assays (ELLBA).
AB  - It was demonstrated that soybean agglutinin and peanut agglutinin aggregated all
      the investigated species of Leishmania, including virulent and avirulent members
      of L. major in agglutination tests. Concanavalin A and Pisum sativum agglutinin
      were shown to aggregate L. species ZMA and L. major but showed no effect on L.
      gymnodactyli and L. mexicana amazonensis which were aggregated by wheat germ
      agglutinin, an extract from Ulex europaeus and Ricinus communis. There was no
      correlation between the results of ELLBA studied in agglutination tests. The
      results indicate that the surfaces of Leishmania strains and species are
      heterogeneous with respect to lectin binding. There are possibly two subsets of
      lectin receptors on the surface structures of Leishmania cells.

PMID- 8289845
TI  - Ion-transporting ATPases: reverse genetics and direct logic.

PMID- 8289846
TI  - [Expression of the gag-precursor of the human T-cell leukemia virus type I in
      Escherichia coli: study of the stability and antigenic properties of virus
      specific hybrid proteins].
AB  - A set of recombinant plasmids containing sequences of HTLV-I viral gag-gene has
      been constructed on the basis of pUR290-pUR292 vector plasmids. The resulting
      hybrid proteins containing different fragments of GAG-precursor in the C-end of
      beta-galactosidase differed to a large extent in stability in Escherichia coli
      cells. The presence of an N-end fragment of GAG-precursor in the recombinants
      decreases drastically their resistance to bacterial proteases. Elimination of the
      fragment resulted in obtaining the recombinant plasmid pGdN coding for high rate
      synthesis (up to 30% of total cellular protein) of gag-specific hybrid
      polypeptide in Escherichia coli HB101 cells. This 145 kDa protein efficiently
      interacts with HTLV-I positive sera. It can be used in diagnostic test-systems
      for indicating HTLV-I infected persons.

PMID- 8289847
TI  - Simple inexpensive method for the efficient purification of PCR products.

PMID- 8289848
TI  - Some new aspects of plant genetic engineering.

PMID- 8289849
TI  - A randomized study of the effects of aerobic exercise by lactating women on
      breast-milk volume and composition.
AB  - BACKGROUND: The potential risks and benefits of regular exercise during lactation
      have not been adequately evaluated. We investigated whether regular aerobic
      exercise had any effects on the volume or composition of breast milk. METHODS:
      Six to eight weeks post partum, 33 sedentary women whose infants were being
      exclusively breast-fed were randomly assigned to an exercise group (18 women) or
      a control group (15 women). The exercise program consisted of supervised aerobic
      exercise (at a level of 60 to 70 percent of the heart-rate reserve) for 45
      minutes per day, 5 days per week, for 12 weeks. Energy expenditure, dietary
      intake, body composition, and the volume and composition of breast milk were
      assessed at 6 to 8, 12 to 14, and 18 to 20 weeks post partum. Maximal oxygen
      uptake and the plasma prolactin response to nursing were assessed at 6 to 8 and
      18 to 20 weeks. RESULTS: The women in the exercise group expended about 400 kcal
      per day during the exercise sessions but compensated for this energy expenditure
      with a higher energy intake than that recorded by the control women (mean [+/-
      SD], intake, 2497 +/- 436 vs. 2168 +/- 328 kcal per day at 18 to 20 weeks; P <
      0.05). Maximal oxygen uptake increased by 25 percent in the exercising women but
      by only 5 percent in the control women (P < 0.001). There were no significant
      differences between the two groups in maternal body weight or fat loss, the
      volume or composition of the breast milk, the infant weight gain, or maternal
      prolactin levels during the 12-week study. CONCLUSIONS: In this study, aerobic
      exercise performed four or five times per week beginning six to eight weeks post
      partum had no adverse effect on lactation and significantly improved the
      cardiovascular fitness of the mothers.

PMID- 8289850
TI  - Coronary-artery vasoconstriction induced by cocaine, cigarette smoking, or both.
AB  - BACKGROUND: In humans, the use of cocaine and cigarette smoking each increase the
      heart's metabolic need for oxygen but may also decrease the supply of oxygen. As
      cocaine abuse has proliferated, cocaine-associated chest pain, myocardial
      infarction, and sudden death have occurred, especially among smokers. We assessed
      the influence of intranasal cocaine and cigarette smoking, alone and together, on
      myocardial oxygen demand and coronary arterial dimensions in subjects with and
      subjects without coronary atherosclerosis. METHODS: In 42 smokers (28 men and 14
      women; age, 34 to 79 years; 36 with angiographically demonstrable coronary artery
      disease), we measured the product of the heart rate and systolic arterial
      pressure (rate-pressure product) and coronary arterial diameters before and after
      intranasal cocaine at a dose of 2 mg per kilogram of body weight (n = 6), one
      cigarette (n = 12), or intranasal cocaine at a dose of 2 mg per kilogram followed
      by one cigarette (n = 24). RESULTS: No patient had chest pain or ischemic
      electrocardiographic changes after cocaine use or smoking. The mean (+/- SE) rate
      pressure product increased by 11 +/- 2 percent after cocaine use (n = 30, P <
      0.001), by 12 +/- 4 percent after one cigarette (n = 12, P = 0.021), and by 45 +/
      5 percent after both cocaine use and smoking (n = 24, P < 0.001). As compared
      with base-line measurements, the diameters of nondiseased coronary arterial
      segments decreased on average by 7 +/- 1 percent after cocaine use (P < 0.001),
      by 7 +/- 1 percent after smoking (P < 0.001), and by 6 +/- 2 percent after
      cocaine use and smoking (P < 0.001). The diameters of diseased segments decreased
      by 9 +/- 2 percent after cocaine use (n = 18, P < 0.001), by 5 +/- 5 percent
      after smoking (n = 12, P = 0.322), and by 19 +/- 4 percent after cocaine use and
      smoking (n = 12, P < 0.001). The increase in the rate-pressure product and the
      decrease in the diameters of diseased segments caused by cocaine use and smoking
      together were greater (P < 0.001 and P = 0.037, respectively) than the changes
      caused by either alone. CONCLUSIONS: The deleterious effects of cocaine on
      myocardial oxygen supply and demand are exacerbated by concomitant cigarette
      smoking. This combination substantially increases the metabolic requirement of
      the heart for oxygen but simultaneously decreases the diameter of diseased
      coronary arterial segments.

PMID- 8289851
TI  - Hyperandrogenism in polycystic ovary syndrome. Evidence of dysregulation of 11
      beta-hydroxysteroid dehydrogenase.
AB  - BACKGROUND: Hyperandrogenemia is the hallmark of the polycystic ovary syndrome,
      yet the relative contributions of the adrenal cortex and ovary to the
      overproduction of androgen remain unclear. To identify possible causes of
      adrenocortical overactivity, we studied the metabolism of adrenal and ovarian
      steroid hormones in women with this disorder. METHODS: We measured 24-hour
      urinary excretion of steroid hormone metabolites by high-resolution capillary gas
      chromatography in 65 women with the polycystic ovary syndrome and 45 normal women
      matched for body-mass index. RESULTS: After adjustment for body-mass index, the
      urinary excretion of testosterone and androstenedione metabolites was 1.9 times
      higher in the women with the syndrome than in the normal women, and the excretion
      of dehydroepiandosterone metabolites (C19 steroid sulfates) and cortisol
      metabolites was 1.5 and 1.3 times higher, respectively (P < 0.01 for all
      comparisons). The affected women also had significantly higher ratios of 11-oxo
      (oxygenated) metabolites to 11-hydroxy metabolites of cortisol (1.4 times higher,
      P < 0.001) and of 11-oxo to 11-hydroxy metabolites of corticosterone (1.8 times
      higher, P < 0.001). In the group with the polycystic ovary syndrome, 55 percent
      of the nonobese women and 24 percent of the obese women had ratios above the
      upper limit of normal; the ratios in the obese women did not differ significantly
      from those in the nonobese women. CONCLUSIONS: Adrenal secretion of cortisol and
      androgens is increased in women with the polycystic ovary syndrome. The increases
      may be explained by dysregulation of 11 beta-hydroxysteroid dehydrogenase causing
      increased oxidation of cortisol to cortisone, which cannot be accounted for by
      obesity.

PMID- 8289852
TI  - Brief report: hypothyroidism caused by chronic autoimmune thyroiditis in very
      young infants.

PMID- 8289853
TI  - Brief report: umbilical-cord ligation of an acardiac twin by fetoscopy at 19
      weeks of gestation.

PMID- 8289854
TI  - Images in clinical medicine. Multiple myeloma.

PMID- 8289855
TI  - Variation in approval by insurance companies of coverage for autologous bone
      marrow transplantation for breast cancer.
AB  - BACKGROUND: The proper evaluation of new forms of technology depends on the
      results of clinical trials. However, the treatment of patients in grant-sponsored
      clinical trials of cancer therapy usually requires that the proposed treatment be
      approved in advance by an insurance carrier in a process called predetermination.
      METHODS: We examined the consistency of predetermination decisions by insurance
      companies for 533 patients enrolled in grant-supported clinical trials of high
      dose chemotherapy and autologous bone marrow transplantation (ABMT) for breast
      cancer from 1989 through 1992. These decisions about coverage were compared with
      peer-reviewed decision making according to the study protocol and with clinical
      outcomes. RESULTS: Requests for insurance coverage for ABMT were approved in 77
      percent of the cases. Of these patients, 23 percent did not undergo bone marrow
      transplantation for protocol-based or medical reasons. Insurance coverage for
      ABMT was denied in response to the other requests, primarily because the therapy
      was considered experimental; of these patients, 51 percent eventually underwent
      bone marrow transplantation despite the denial of insurance. In some instances,
      the patient had to hire an attorney to gain coverage. The frequency of approval
      was not influenced by the pretreatment clinical characteristics of the patients,
      the design or phase of the study, the year in which the predetermination request
      was made, or the response to induction therapy. There was substantial
      inconsistency in the frequency of approval of coverage both among insurers and
      between decisions made by some individual insurers, even for patients in the same
      study protocol. CONCLUSIONS: The predetermination process as applied to patients
      receiving care in clinical research trials of cancer therapy was arbitrary and
      capricious. Although most of the patients eventually received financial coverage
      for entry into clinical trials, the process of predetermination by insurers did
      not correlate with protocol-based medical decision making, and it was a barrier
      to obtaining treatment.

PMID- 8289856
TI  - The treatment of multiple myeloma.

PMID- 8289857
TI  - Life, death, and the insurance companies.

PMID- 8289858
TI  - Conflicts of interest.

PMID- 8289859
TI  - . . . and the Journal's policies.

PMID- 8289860
TI  - . . . and the Journal's policies.

PMID- 8289861
TI  - Thrombolytic therapy for acute myocardial infarction: GUSTO criticized.

PMID- 8289862
TI  - Thrombolytic therapy for acute myocardial infarction: GUSTO criticized.

PMID- 8289863
TI  - Plasma renin activity and ischemic heart disease.

PMID- 8289864
TI  - Warfarin and aspirin after heart-valve replacement.

PMID- 8289865
TI  - Warfarin and aspirin after heart-valve replacement.

PMID- 8289866
TI  - Variation in the prothrombin-time ratio during oral anticoagulation.

PMID- 8289867
TI  - Variation in the prothrombin-time ratio during oral anticoagulation.

PMID- 8289868
TI  - Variation in the prothrombin-time ratio during oral anticoagulation.

PMID- 8289869
TI  - Cocaine-induced coronary-artery dissection.

PMID- 8289870
TI  - Clinical problem-solving: prevention of meningococcal infection.

PMID- 8289871
TI  - Clinical problem-solving: prevention of meningococcal infection.

PMID- 8289872
TI  - Strategies for drug discovery.

PMID- 8289873
TI  - Toward the design of new inhibitors: a computer modeling approach.

PMID- 8289874
TI  - Efforts to improve the utilization of protein sequence and structure databases.

PMID- 8289875
TI  - Use of computer graphics in drug design.

PMID- 8289876
TI  - Purification and cloning of opioid receptors.

PMID- 8289877
TI  - Computer-assisted design of dopamine transporter ligands.

PMID- 8289878
TI  - The pharmacophore for opioid activity.

PMID- 8289879
TI  - Molecular determinants of cannabinoid activity: toward the design of cannabinoid
      analgesics with reduced psychoactive liability.

PMID- 8289880
TI  - Cocaine receptor: a structure-activity relationship study.

PMID- 8289881
TI  - The use of conformational restriction and molecular modeling techniques in the
      development of receptor-specific opioid peptide agonists and antagonists.

PMID- 8289882
TI  - Probes for the cannabinoid sites of action.

PMID- 8289883
TI  - A model for the structural basis of delta 2-opioid receptor selectivity.

PMID- 8289884
TI  - Mass ligand-binding screening strategies for identification of leads for new drug
      discovery.

PMID- 8289885
TI  - Antibody- and peptide structure-based drug design.

PMID- 8289886
TI  - The use of cloned human receptors for drug design.

PMID- 8289887
TI  - Synthetic peptide combinatorial libraries may be used to determine peptide
      ligands for opioid receptors.

PMID- 8289888
TI  - Preparation of large peptide libraries with one peptide per bead and their use
      for the discovery of peptides that bind to acceptors.

PMID- 8289889
TI  - Computer design of bioactive compounds based on 3-D properties of ligands.
AB  - 3-D database searching has many uses for a medicinal chemist. It can aid in the
      design of compounds to probe or to mimic the bioactive conformation of a natural
      ligand or to fit a hypothetical or experimental structure of a binding site. It
      also can identify existing molecules that meet these criteria--new uses for old
      molecules. If one has a database of active compounds, 3-D searching can validate
      or refute a pharmacophore hypothesis. The CoMFA method of 3DQSAR can be used to
      forecast the potency of the designed analogs. Also, the integration of CoMFA and
      3-D searching concepts provides a framework for the design of a good series for
      CoMFA. In addition, CoMFA 3DQSAR coefficients provide a model of the binding site
      to facilitate the design of compounds that fit the pharmacophore and do not hit
      sterically unfavorable regions.

PMID- 8289891
TI  - Cocaine Treatment: Research and Clinical Perspectives. Proceedings of a meeting.
      Bethesda, Maryland, August 16-17, 1990.

PMID- 8289890
TI  - Treatment of cocaine abusers: issues and perspectives.

PMID- 8289892
TI  - Psychotherapeutic treatment of cocaine abuse: models for its evaluation alone and
      in combination with pharmacotherapy.

PMID- 8289893
TI  - Behavioral treatments of cocaine dependence.

PMID- 8289894
TI  - Outpatient treatment of cocaine and crack addiction: a clinical perspective.

PMID- 8289895
TI  - Day hospital vs. inpatient rehabilitation of cocaine abusers: an interim report.

PMID- 8289896
TI  - Cocaine abusers in therapeutic community treatment.

PMID- 8289897
TI  - Community outreach for injection drug users and the need for cocaine treatment.

PMID- 8289898
TI  - Relapse to cocaine use: conceptual issues.

PMID- 8289899
TI  - Pretreatment natural history of cocaine addiction: preliminary 1-year follow-up
      results.

PMID- 8289900
TI  - Combinations of treatment modalities and therapeutic outcome for cocaine
      dependence.

PMID- 8289901
TI  - Treatment of cocaine abuse and dependence: directions and recommendations.

PMID- 8289902
TI  - Comorbid psychiatric disorders and cocaine abuse.

PMID- 8289903
TI  - Clinical and research perspectives on cocaine abuse: the pharmacotherapy of
      cocaine abuse.

PMID- 8289904
TI  - Medications development at the National Institute on Drug Abuse: focus on
      cocaine.
AB  - NIDA's MDD is faced with the formidable task of identifying, characterizing, and
      developing new chemical entities to combat substance abuse. The primary challenge
      is to find one or more medications that will be useful in treating cocaine
      addiction, withdrawal, and abstinence. In addition, a treatment for cocaine
      overdose is in progress. Methodological approaches include testing compounds that
      alter endogenous neurotransmitters and compounds that suppress conditioned cues
      and stimuli. Compounds that appear efficacious in these tasks and that have a
      satisfactory safety profile will be studied in humans.

PMID- 8289905
TI  - Developing treatments that address classical conditioning.
AB  - Repetitive use of psychoactive drugs produces a variety of learned behaviors.
      These can be classified in the laboratory according to an operant/classical
      paradigm, but in vivo the two types of learning overlap. The classical CRs
      produced by drugs are complex and bidirectional. There has been progress in
      classifying and predicting the types of CRs, but little is known of mechanisms.
      New techniques for understanding brain function, such as microdialysis probes in
      animals and advanced imaging techniques (positron emission tomography and single
      photon emission computerized tomography) in human subjects, may be utilized in
      conditioning paradigms to "open the black box." Because the existence of CRs in
      drug users is now well established, clinical studies have been instituted to
      determine whether modification of CRs can influence clinical outcome. A recently
      completed study in cocaine addicts has produced evidence that outcome can be
      improved by a passive extinction technique over an 8-week outpatient treatment
      program.

PMID- 8289906
TI  - Neurobehavioral treatment for cocaine dependency: a preliminary evaluation.
AB  - The treatment of cocaine dependency in the 1980s has required the use of a broad
      range of strategies. Although there are some promising approaches for treating
      certain aspects of the cocaine withdrawal syndrome, there is no empirical
      evidence that provides a clear direction to the future development of a
      comprehensive treatment approach. The neurobehavioral model is an initial attempt
      to structure information, support, and encouragement across a series of stages
      that are experienced by cocaine abusers as they progress through the first 6
      months of their recovery. This model attempts to sequence strategies in a way
      that will correspond to an expected timetable of problem emergence during
      recovery from cocaine dependency. Individual sessions with trained therapists are
      used extensively to move clients through the recovery process. Relapse prevention
      techniques have been used extensively within a relapse prevention group format
      and in a standardized relapse analysis procedure. This model has been
      standardized into a manual that allows for replication and evaluation. Current
      research efforts are under way to assess the usefulness of this model as an
      independent treatment approach and as a framework for evaluating other
      potentially useful cocaine dependency treatment strategies.

PMID- 8289907
TI  - Assessing Neurotoxicity of Drugs of Abuse. Proceedings of a meeting. Bethesda,
      Maryland, May 20-21, 1991.

PMID- 8289908
TI  - Neurobehavioral methods used in neurotoxicology.
AB  - The use of neurobehavioral techniques in toxicology has increased dramatically
      over the past several years. Several national and international groups have
      recommended that neurobehavioral tests be included in the initial stages of
      hazard identification, and regulatory agencies have responded by preparing
      testing guidelines or requiring behavioral tests data for premarket approval of
      environmental and pharmaceutical chemicals. In addition, neurobehavioral data
      have been used to set exposure limits in the workplace. In the future,
      neurobehavioral data will be used more frequently in the area of risk assessment,
      which has been defined as the "characterization of the potential adverse effects
      of human exposure to environmental hazards" (National Academy of Sciences 1983).
      Good risk assessment depends on the ability to determine whether a particular
      agent is or is not causally linked to a particular health effect and on the
      availability of dose-response data for quantitative risk assessment.
      Neurobehavioral techniques used in animal behavioral toxicology measure
      neurobiological functions similar to those measured in humans. In addition,
      neurobehavioral procedures can be used in longitudinal studies where the onset
      and duration of effects of chemical exposure can be measured in the same animal.
      Neurobehavioral techniques are also amenable to the study of tolerance and
      compensation following repeated exposure or following recovery of function that
      can occur following cessation of exposure. Therefore, neurobehavioral procedures
      provide a valuable tool for research designed to reduce major uncertainties
      associated with the risk assessment process, such as animal to human
      extrapolation (homology of animal models) and dosing issues (i.e., high-to-low
      dose, acute vs. repeated dosing, and continuous vs. episodic dosing). Although
      the use of neurobehavioral procedures has had a significant impact on
      neurotoxicology, their use in the risk assessment process and in monitoring
      populations for possible subtle changes in neurobiological function will be
      limited if additional research is not done to understand the neural substrates
      underlying neurobehavioral endpoints. The ability to link chemically induced
      behavioral changes to alterations at the neurophysiological, neurochemical, and
      neuroanatomical levels will lead to a greater acceptance of the validity and
      reliability of neurobehavioral endpoints in defining adverse effects of chemicals
      on the nervous system.

PMID- 8289909
TI  - Silver staining as a tool for neurotoxic assessment.
AB  - There is no denying that the silver methods lost their dominant role as tract
      tracing methods in the past 10 to 15 years. But it seems equally clear that the
      silver technique is headed for a dramatic revival in many fields of neuroscience,
      where the scope and localization of neuronal degeneration are a central issue.
      Together with the immunostaining of proteins formed or altered in traumatized
      neurons, the modern silver techniques provide neurotoxicologists and
      neuropathologists with unparalleled opportunities to detect and study injured and
      dying neurons. Characterized by great sensitivity and distinct rendition of the
      morphology of degenerating neurons and their processes, the reduced silver
      methods constitute the ideal tool for screening irreversible neuronal damage
      caused by neurotoxic substances including drugs of abuse. Those interested in the
      rapidly expanding fields of "excitotoxicity" and neurodegenerative disorders
      (Taylor 1991) are also likely to find increasing use for the silver methods. The
      pattern of degeneration in so-called "system degenerations" may be predetermined
      by the neuronal connections (Saper et al. 1987), and as the disease progresses
      from the destruction of the originally affected neuron population, closely
      related systems and pathways may be recruited into the pathophysiologic cascade.
      Any type of trauma to the CNS has the potential to produce this type of "domino
      effect" of degeneration, through which additional systems are progressively
      recruited into a degenerative chain reaction of transneuronal degeneration. In
      other words, even longstanding disorders may exhibit signs of more recent
      degeneration, and the proper use of silver methods at autopsy may give some
      important clues regarding the etiology of disease; it may also provide new
      insights about the anatomy of the human brain. Little can be said at present
      about the chemical basis of argyrophilia in degenerating and "reactive" neurons,
      but there is every reason to pay more attention to this subject. One can expect
      that a continuing and concerted effort will result in a rational understanding of
      the molecular biological and physicochemical events that fortuitously provide the
      basis for the selective impregnation of degenerating neuronal elements. This
      knowledge can be the basis for the development of even more reliable and simple,
      yet sensitive, silver methods suited for neurotoxic risk assessment on a large
      scale.

PMID- 8289910
TI  - Reactions of 5-HT neurons to drugs of abuse: neurotoxicity and plasticity.

PMID- 8289911
TI  - Quantification of reactive gliosis as an approach to neurotoxicity assessment.

PMID- 8289912
TI  - Neurotoxicity and drugs of abuse: cannabinoid interaction with brain
      glucocorticoid receptors.

PMID- 8289913
TI  - Behavioral consequences of partial monoamine depletion in the CNS after
      methamphetamine-like drugs: the conflict between pharmacology and toxicology.

PMID- 8289914
TI  - Strategies for detecting subclinical monoamine depletions in humans.
AB  - Given the reported increase in the recreational use of controlled substance
      analogs such as MDMA and related drugs, it is important to determine whether
      these drugs produce neurotoxic effects in humans. Several strategies available
      for detecting preclinical neurotoxicity to dopamine and serotonin neurons have
      been discussed, and their strengths and limitations have been listed. In
      addition, some promising strategies that are still in the development stage
      (e.g., PET) have been mentioned. None of the available methods for detecting
      neurotoxicity is conclusive; therefore, converging lines of evidence will be
      essential to provide convincing indication of subclinical neurotoxicity in
      humans. Such studies will help define the public health risk of recreationally
      used drugs. Furthermore, documentation and determination of drug-induced
      neurotoxic changes may shed light on the pathophysiology of idiopathic
      neurodegenerative diseases involving monoaminergic neurons in humans and could be
      useful in the development of new treatment strategies. Finally, detailed
      neuropsychiatric evaluation of individuals with confirmed subclinical
      serotonergic neurotoxicity may enhance knowledge regarding the functional role of
      brain serotonin neurons in health and disease.

PMID- 8289915
TI  - Sensory-evoked potentials: measures of neurotoxicity.

PMID- 8289916
TI  - Behavioral Treatments for Drug Abuse and Dependence. Proceedings of a meeting.
      Bethesda, Maryland, September 1-2, 1992.

PMID- 8289917
TI  - Cognitive therapy of substance abuse: theoretical rationale.
AB  - In this chapter, the authors assert that drug-related beliefs are an important
      factor in drug abuse and its treatment. Three types of acute drug-related beliefs
      have been described that contribute to urges, cravings, and ultimate use of
      drugs: anticipatory beliefs, relief-oriented beliefs, and permissive beliefs, and
      various ways have been described to assess more general, long-term beliefs
      pertinent to drug use. The role of the cognitive therapist is to assess, examine,
      and test these beliefs with the patient in order to ultimately develop more
      adaptive beliefs. The active application of skills and homework that tap into the
      patient's adaptive beliefs helps the patient to become and remain drug-free.

PMID- 8289918
TI  - Harm reduction: application to alcohol abuse problems.

PMID- 8289919
TI  - Behavioral treatments for drug problems: lessons from the alcohol treatment
      outcome literature.
AB  - Behavioral approaches have a strong track record in the treatment of alcohol
      problems. They are generally cost-effective (Holder et al. 1991), can be readily
      combined with and enhance the effectiveness of pharmacologic interventions (e.g.,
      Azrin et al. 1982), and have been found to be applicable all along the continuum
      of problem severity. Cognitive-behavioral strategies appear to be particularly
      helpful in addressing common problems of treatment motivation, retention, and
      compliance. There is no reason to expect substantially different findings when
      behavioral strategies are applied in the treatment of other drug problems.

PMID- 8289920
TI  - Multisystemic treatment of serious juvenile offenders: implications for the
      treatment of substance-abusing youths.
AB  - MST has proven to significantly decrease rates of antisocial behavior in serious
      juvenile offenders. In light of the similarities between the problems of
      delinquency and adolescent substance abuse, MST holds promise as an effective
      treatment of the latter. Hence, conceptual, clinical, and service delivery
      features of MST are presented.

PMID- 8289921
TI  - Contingency management in methadone treatment: the case for positive incentives.

PMID- 8289922
TI  - Dialectical behavior therapy for treatment of borderline personality disorder:
      implications for the treatment of substance abuse.

PMID- 8289923
TI  - Substance abuse research: outcome measurement conundrums.

PMID- 8289924
TI  - Between-group therapy outcome research: design and methodology.

PMID- 8289925
TI  - When clinical trials fail: a guide to disaggregation.

PMID- 8289926
TI  - Behavioral treatments for drug problems: where do we go from here?

PMID- 8289927
TI  - Clinicwide and individualized behavioral interventions in drug dependence
      treatment.

PMID- 8289928
TI  - Advancing the application of behavioral treatment approaches for drug dependence.

PMID- 8289929
TI  - Cue reactivity and cue reactivity interventions in drug dependence.
AB  - Despite a venerable history dating back to Pavlov and countless testimonials from
      patients such as those in the opening paragraphs of this chapter, there is much
      that remains to be learned about drug signals and, particularly, about ways of
      reducing their adverse effects on human drug users. There is a substantial amount
      of data showing increased craving and signs of physiological arousal to drug
      related versus neutral cues in drug users for both drug classes reviewed here.
      Additional controlled studies will be useful in refining which responses among
      those studied are, in fact, conditioned in origin and therefore can be subjected
      reasonably to learning-based interventions. Most attempts to modify cue
      responsivity for clinical benefit have met with only modest success, and there is
      ample room for creative, but controlled, treatment-outcome studies. In recent
      years, several other groups have joined in the effort to understand drug-related
      cue reactivity, extending the research area to alcohol and nicotine (Monti et al.
      1987; Niaura et al. 1988, 1989; Cooney et al. 1984; Hodgson and Rankin 1982;
      Drummond 1990; Laberg 1990). The interested reader is referred to several
      additional reviews of cue reactivity and cue exposure research related to alcohol
      and nicotine (Niaura 1988; Drummond 1990; Laberg 1990), opiates (Powell 1990),
      opiates and cocaine (Childress et al. 1988b; O'Brien et al. 1990), and all the
      preceding areas (Rohsenow et al. 1991).

PMID- 8289930
TI  - Treatment of cocaine dependence through the principles of behavior analysis and
      behavioral pharmacology.

PMID- 8289931
TI  - Legislative issues, breakthroughs in ESRD care highlight NKF/ASN meetings.

PMID- 8289933
TI  - A patient/facility contract can have value beyond handling noncompliance.

PMID- 8289932
TI  - What hemodialysis patients want and need.

PMID- 8289934
TI  - FDA reconsiders dialyzer relabeling plan after meeting with renal community.

PMID- 8289935
TI  - HCFA, Minntech continue battle over use of data from reuse studies.

PMID- 8289936
TI  - [1 year following the airplane disaster in the Bijlmermeer; post-traumatic
      reactions in a family practice].

PMID- 8289937
TI  - [Admission in a nursing home: necessity or virtue?].

PMID- 8289938
TI  - [Selection of medical residents for education in surgery in The Netherlands].

PMID- 8289939
TI  - [1993 Nobel Prize for Medicine for the discovery of split genes].

PMID- 8289940
TI  - [Recurrent dislocation of the peroneal tendon].

PMID- 8289941
TI  - [Sweet's syndrome (acute febrile neutrophilic dermatosis)].
AB  - The clinical presentation and the relation with malignancy of acute febrile
      neutrophilic dermatosis in 7 patients are described. The syndrome is
      characterised by fever, neutrophilic granulocytosis, painful erythematous plaques
      and typical histology consisting of a dense dermal infiltrate of mature
      neutrophils. The idiopathic form (80% of reported patients) usually follows a
      viral infection. The secondary form (20% of reported patients) is associated with
      a malignancy, which in the large majority (85%) is a hematologic disorder (this
      was the case in 3 of the 7 patients); the course of the syndrome may then be
      serious. The secondary form of the disease may be associated with an exacerbation
      of a preexistent malignancy, as was seen in 2 of the 3 patients. If the syndrome
      runs a serious course the treatment consists of corticosteroid administration.

PMID- 8289942
TI  - [Neurologic consultation in cancer patients].
AB  - OBJECTIVE: To inventory neurological complications in patients with cancer.
      DESIGN: Descriptive study. SETTING: University Hospital Vrije Universiteit,
      Amsterdam. METHOD: Data were collected from 718 neurological consultations with
      610 admitted oncological patients from 1990 to 1992. RESULTS: In 203 cases
      backache, sometimes radiating to the leg, prompted the request for neurological
      consultation. In 142 cases a metastasis in the vertebrae could be detected; in 64
      cases there were signs and/or symptoms of compression. Cerebral metastasis
      occurred in 133 patients in which eventuality neurological dysfunctions were the
      main initial manifestations. In all, 32 cases of leptomeningeal metastasis were
      diagnosed, mostly associated with carcinoma of the breast or haematological
      system. In 30 cases there was growth of a primary tumour or metastasis into a
      plexus or peripheral nerve. Non-metastatic complications consisted of
      paraneoplastic, iatrogenic and other (mostly metabolic or toxic encephalopathy)
      causes. A paraneoplastic complication was seen in only 6 cases. Iatrogenic
      complications were most frequently caused by cytotherapy. CONCLUSION: Numerous
      neurological complications can occur in patients with cancer. Timely treatment of
      metastatic complications can prevent serious disablement in a terminal stadium of
      the disease.

PMID- 8289943
TI  - [HIV infection and unsafe sexual behavior among young homosexual men in
      Amsterdam, 1992].
AB  - OBJECTIVE: To determine the prevalence of sexual behaviour with the risk of HIV
      transmission among young homosexual men in Amsterdam. DESIGN: Point prevalence
      study. SETTING: Amsterdam. METHODS: Participants were recruited through
      advertisements and in gay bars and a STD clinic in the period October 1991-1992.
      A questionnaire regarding sexual behaviour was completed, and blood samples were
      drawn to test for presence of serological markers of HIV infection, hepatitis B
      and syphilis. RESULTS: Enrolled in the study were 154 men (mean age: 25 years).
      The prevalence of antibodies against HIV was 5% and that of hepatitis B 22%.
      Receptive anogenital intercourse with steady partners in the previous six months
      was reported by 60% (74% sometimes without a condom), with non-steady partners by
      41% (40% without a condom). The figures for insertive anogenital intercourse
      were: steady partners: 45% (74%); non-steady partners: 49% (41%). Overall 43%
      (66/153) reported at least one unprotected anogenital contact in the previous six
      months. The presence of HIV antibodies was correlated with the number of partners
      with whom anogenital sexual intercourse was practised. CONCLUSION: The HIV
      prevalence (5%) was relatively low. Considering the high prevalence of unsafe
      sexual behaviour further spread of HIV infection among young homosexual men is to
      be expected.

PMID- 8289944
TI  - [Hemolytic disease in a newborn infant caused by rare maternal anti-erythrocyte
      antibodies and exchange transfusion with maternal blood frozen earlier].
AB  - After a pregnancy of 31 weeks and 4 days a pale baby girl was born with mild
      oedema, severe anaemia (4.2 mmol/l), increased normoblast count and
      hyperbilirubinaemia, indicating a blood group antagonism. This was caused by very
      rare irregular antibodies with the specificity anti-U. These antibodies had been
      demonstrated in the mother before, after earlier transfusions with erythrocytes.
      At that time autologous blood was stored at -70 degrees C in the Central
      Laboratory of the Dutch Red Cross in Amsterdam, because U negative donors are
      hard to find. One of these units was used for an exchange transfusion given to
      the baby, who recovered well. This case study underlines the necessity of
      screening for presence of irregular antibodies during pregnancy. A national
      registration of patients with antibodies against erythrocytes is recommended.

PMID- 8289945
TI  - [Echinococcosis in The Netherlands, 1987-1991].

PMID- 8289946
TI  - [Extramural nursing home care: day care, consultation and substitution projects].

PMID- 8289947
TI  - [Selection of medical residents for medical specialist education: experiences
      with a structured procedure].
AB  - OBJECTIVE: Evaluation of an objective, standardised method for selection of
      residents for medical specialty training. DESIGN: Retrospective. SETTING:
      University Hospital Utrecht, department of diagnostic radiology. Utrecht
      University, Department of Clinical Psychology and Health Psychology. METHODS: All
      applicants for residency positions in 1990-1991 were requested to complete a
      standard application form. The applications were judged by seven staff members on
      six criteria. Using statistical tests the relative contribution of each criterium
      was calculated. A similar procedure was followed for those who were invited for
      an interview. RESULTS: Most of the criteria applied for the written and oral
      applications contributed significantly to the rank order achieved. The written
      and oral criteria showed some degree of overlap, whilst the criteria used for the
      written application were relatively independent from those used for the
      interview. For a balanced evaluation of the written information a selection
      committee of four staff members was sufficient. CONCLUSION: Structuring the
      selection process as described gives both staff and applicants more insight in
      the criteria applied, and thus allows a more objective and valid evaluation. To
      medical students it is beneficial to become acquainted with criteria that may be
      used in selection procedures for medical specialty training, so they can prepare
      themselves adequately.

PMID- 8289948
TI  - [Hyperventilation: not a cause of panic attacks].

PMID- 8289949
TI  - [Hyperventilation: not a cause of panic attacks].

PMID- 8289950
TI  - [Estimation of the chance of transmission of HIV or hepatitis B infection in
      ambulatory dependence care].

PMID- 8289951
TI  - [Current developments in the area of multiple sclerosis].

PMID- 8289952
TI  - [The pill and cancer of the female sex organs and breast].

PMID- 8289953
TI  - [A facial fistula; generally not a skin disorder].

PMID- 8289954
TI  - [Assessment of indications using the RAND method: invasive therapy in coronary
      sclerosis as an example].
AB  - OBJECTIVE: To assess indications for performing medical procedures for their
      appropriateness, using a method designed by an American research institute, RAND.
      DESIGN: Delphi investigation SETTING: The Netherlands. METHOD: The RAND method
      was applied in the 'Dutch inventory of invasive coronary atherosclerosis
      treatments' study which concerns treatment choices in coronary artery disease:
      coronary artery bypass grafting (CABG), percutaneous transluminal coronary
      angioplasty (PTCA) and conservative treatment. Essential in the RAND method is
      the construction of a comprehensive matrix of potential indications. Each
      indication entails a comparison of two or three treatment options. A panel of 12
      experts rated each indication in a two-stage process. When the majority of the
      panelists agreed that treatment option X was strongly to be preferred over Y, it
      was considered appropriate to perform X and inappropriate to perform Y. RESULTS:
      The experiences with the RAND method indicated that panelists judged critically
      and rated many indications for invasive treatment options as inappropriate or
      uncertain. The method was feasible, although not easy, and produced clinically
      valid results. CONCLUSION: The RAND method is especially useful when medical
      literature does not supply sufficient grounds in rating the appropriateness of an
      indication for medical procedure. However, the verdict 'appropriate' is not
      eternal. Medical science keeps evolving.

PMID- 8289955
TI  - [Costs of autologous bone marrow transplantation in non-Hodgkin lymphoma and
      acute leukemia].
AB  - OBJECTIVE: To estimate the costs of an autologous bone marrow transplantation
      (auto BMT) for patients with non-Hodgkin lymphoma and patients with acute
      lymphoid leukaemia. DESIGN: Cost analysis. SETTING: Five Dutch hospitals. METHOD:
      By means of detailed cost registration forms, interviews with haematologists,
      research nurses, research analysts and hospital information systems, the costs of
      auto BMT were estimated. RESULTS: The costs of an auto BMT were estimated at f
      63,400 per patient with non-Hodgkin lymphoma and at f 86,400 for patients with
      acute leukaemia. The latter patients stayed longer in hospital and needed more
      intensive isolation care, more blood transfusions and more antibiotics.
      CONCLUSION: These data are important when the Medical Insurance Board decides on
      provision for this treatment.

PMID- 8289956
TI  - [Markedly varying physiotherapeutic treatment following carpal injuries].
AB  - OBJECTIVE: To inventory long-term symptomatic and physiotherapeutic results in
      patients treated conservatively for a carpal injury. DESIGN: Follow-up
      investigation and case control study. SETTING: University Medical Centre,
      Amsterdam. METHOD: A follow-up investigation was conducted in a group of 100
      patients with carpal injury. In this group clinical parameters of patients
      treated conservatively and with physiotherapy (PT) (n = 16) were compared with 16
      case controls without PT, selected for age, sex, diagnosis and duration of
      immobilisation. RESULTS: After removal of the plaster cast, 16 patients had been
      referred to a physiotherapist because pain was a major complaint. PT was given 2
      3 times a week for an average of 11 days after a period of immobilisation of
      about 9.5 weeks. Treatment varied strongly among the physiotherapists. Follow-up
      took place 13-50 months after injury. Patients treated with PT had significantly
      more complaints concerning the traumatised hand than patients without PT. In the
      long run only 2 patients benefited from PT. CONCLUSION: Physiotherapy after
      carpal injury lacks method. Applications were arbitrary added or omitted.
      Patients with carpal injury who were treated with physiotherapy after
      immobilisation had more complaints in the long run. This difference may be due to
      selectivity in the policy of referring for physiotherapy.

PMID- 8289957
TI  - [Hepatosplenic candidiasis in patients treated for hemato-oncological disorders].
AB  - Hepatosplenic candidiasis is increasingly observed in patients with a
      haematological malignancy who have received chemotherapy. A case history is
      described of a male aged 45 who developed symptoms of hepatosplenic candidiasis
      caused by Candida tropicalis after treatment for acute myeloid leukaemia. The
      disease is characterized by persistent fever after recovery of the leukopenia
      induced by the chemotherapy. Echographic and computer-tomographic examination may
      reveal abscess patterns specific of Candida in the liver. Treatment consists of
      amphotericin B intravenously or fluconazole orally. Protracted treatment is
      frequently required.

PMID- 8289958
TI  - [Uterine inversion].
AB  - Inversion of the uterus is a rare complication of childbirth. A primigravida aged
      21 and a multigravida aged 32, hospitalized as emergency cases because of
      inversion of the uterus with major blood loss, were treated with infusion of
      liquids (to combat shock), repositioning of the uterus under anaesthesia and
      prevention of reinversion by uterine tonics. Inversion of the uterus should be
      part of the differential diagnosis in every case of fluxus post partum.

PMID- 8289959
TI  - [Appropriate use of the concept 'appropriate' in discussions on health care].

PMID- 8289960
TI  - [Vietnam back in perspective; reforms also concern health care].

PMID- 8289961
TI  - [No advantage in the addition of dipyridamole to, or of oral anticoagulants in
      comparison to, a low dose of acetylsalicylic acid (50 mg per day) in the
      prevention of venous transplant stenosis following coronary bypass surgery].

PMID- 8289962
TI  - [The clinical diagnostic significance of magnetic stimulation studies].

PMID- 8289963
TI  - [Treatment of multiple sclerosis using recombinant interferon-beta].

PMID- 8289964
TI  - Acute myeloid leukemia: correlation between purine metabolism enzyme activities
      and membrane immunophenotype.
AB  - A total of 34 AML patients with heterogenous age distribution (from 2 years up to
      82 years) were observed. Purine metabolism enzyme activities were compared and
      correlated with membrane immunophenotype. Analysis of bone marrow and peripheral
      blood samples based on FAB criteria and immunologic phenotyping of acute myeloid
      leukemia (AML) provided useful--either confirmatory or contradictory-information
      on the distribution of M1-M6 patients demonstrating a predominance of M1+M2 and
      M4 groups (44% and 32.4%, respectively). In contrast, it was demonstrated that
      less frequent subtypes were M3 and M6 (5.9% and 2.9%, respectively). AML subtypes
      were correlated with expression of surface antigens detected by the following
      monoclonal antibodies: CD13, CD33, CDw65, CD11b, CD15, CD14, HLA-DR and CD34. On
      the basis of immunophenotyping we found the following characteristic markers: M1,
      M2-CD34, HLA-DR, CD13, CD33, CDw65; M3-CD13, CD33, HLA-DR (negative); M4, M5
      CDw65, CD14, CD13, CD33 and HLA-DR. CD14 was confirmed to be a typical marker for
      discriminating myeloid from monocytoid FAB AML subtypes. Analysis of purine
      metabolism enzyme activities showed that there is a correlation between the
      values of adenosine deaminase and purine nucleoside phosphorylase and various
      immunotypes of AML. High ADA/PNP ratio (> 1.0) was found in M1, M2, M3 subtypes.
      It was due to the increased level of ADA activity (> 100 pkat.10(-6) cells),
      though these activities overlapped to a certain extent. It was shown that PNP
      activity simultaneously decreased. With maturation of cells within AML lineage
      ADA activity decreased and PNP activity increased. This corresponded with ADA/PNP
      ratio that was < 1.0 in cells of more mature AML subtypes. We found that the
      enzymatic values were characteristic mainly in cells of M5 (monocytic) AML
      subtype and were characterized by decreased values of ADA activity with a
      simultaneous increase in PNP activity. It follows from our results that ADA/PNP
      ratio enables to discriminate between myeloid and monocytoid subtypes of AML.

PMID- 8289965
TI  - Immunoglobulin levels in children treated for malignant tumors.
AB  - IgG, IgA and IgM levels were examined in children treated for different malignant
      tumors. Chemotherapy decreased IgG and mainly IgM. There was increased incidence
      of infectious complications in IgG deficiency.

PMID- 8289966
TI  - Prognostic value of plasma-cell immunophenotype in patients with multiple
      myeloma.
AB  - A review is given of the prognostic significance of immunophenotyping of blood
      lymphoplasmocytic cells. From a group of 250 patients followed from 1981 through
      1991 a subgroup of 70 patients (followed 1986 through 1991) were phenotyped at 6
      month intervals by immunofluorescence tests with monoclonal antibodies for
      cytoplasmic immunoglobulin, kappa-lambda index, CD71, CD10, CD20, CD38, and HLA
      DR receptors. In course of a longitudinal study it was found that prognostic
      significance for shortened survival can be derived from the presence of
      circulating CD10, CD71, and CD20 positive undifferentiated cells in peripheral
      blood. There was a correlation between increase of CALLA positive and CD71
      positive cells. Further, an increase of undifferentiated clone occurred during
      transition of the disease to an aggressive phase. The median survival of the
      total group of 250 patients treated by the VMCP/MOCCA protocol, according to
      statistical analysis, was 90 months, the median survival of the aggressive stage
      with plasmoblastic and lymphoplasmocytic cell type, respectively, was only 12
      months. The significance of phenotypization in the prognostic evaluation of
      variant heterogenous myeloma types is stressed.

PMID- 8289967
TI  - Immunophenotypic significance of the "lymphoid" CD38 antigen in myeloid blood
      malignancies.
AB  - In 72 patients with blood malignancies (leukemias), the expression and
      distribution of the "B-lineage" antigen CD38, was analyzed, individually and in
      combination with CD19, CD10, HLA-DR, CD13, CD14, CD33, CDw65, CD2 and CD7. The
      expression of CD38 on the surface of leukemic cells was totally different from
      its expression on normal hematopoietic cells. Its positivity in myeloid
      malignancies was as follows: In patients with acute myeloid leukemia in 21/28
      cases-75% (probability of expression 0.68 +/- 0.2, p < 0.05) and in patients with
      chronic myeloid leukemia in 4/6 cases-66%. In lymphoproliferative malignancies
      the CD38 antigen was expressed as follows: In patients with acute non-T
      lymphoblastic leukemia in 12/16 cases-75% (probability of expression 0.7 +/- 0.2,
      p < 0.05) and in patients with chronic B lymphocytic leukemia in 6/8 cases-75%.
      CD38 was also found positive in patients with acute mixed lineage leukemia.

PMID- 8289968
TI  - Multiple fractions of gamma rays do not induce overexpression of c-myc or c-Ki
      ras oncogenes in human cervical carcinoma cells.
AB  - Multiple fractions of gamma rays (0.5 Gy daily, 30 fractions) had previously been
      found to change the sensitivity of human cervical carcinoma HeLa cells to
      anticancer drugs. Preirradiated cells became resistant to cisplatin, methotrexate
      and vincristine, but retained the same sensitivity to gamma rays and ultraviolet
      light. Some mechanisms involved in resistance of preirradiated cells to cisplatin
      and vincristine were determined, i.e. the increased levels of metallothioneins
      and increased expression of plasma membrane P glycoprotein. As recent reports
      indicated that the resistance to cisplatin and ionizing radiation may involve
      expression of oncogenes, we examined whether multiple fractions of gamma rays can
      change the expression of c-myc and c-Ki-ras oncogenes in HeLa cells and
      determined whether there is a correlation between expression of these oncogenes
      and sensitivity of preirradiated cells to cisplatin and gamma rays. The
      expression of c-myc and c-Ki-ras oncogenes were examined by the use of DNA dot
      blot, RNA dot blot and Northern blot analyses. The results show that
      preirradiation did not induce either amplification or elevated expression of c
      myc or c-Ki-ras oncogenes. Further, there is no correlation between expression of
      c-myc and c-Ki-ras oncogenes and the acquired resistance to cisplatin.

PMID- 8289969
TI  - Polarographic study of cytosine nucleosides.
AB  - The conditions for polarographic reduction of several nucleic acid components
      were determined. These components were the pyrimidine base cytosine and
      nucleoside cytidine, and its synthetic analogs arabinosylcytosine and
      cyclocytidine hydrochloride which are cytotoxic and antileukemic agents.
      Polarographic reduction, its character and mechanism were studied in aqueous
      conditions of Britton Robinson buffer at different pH and in nonaqueous
      conditions of dry dimethylformamide. It was found that the polarographic wave of
      all compounds had a diffuse character and that the whole process was a two
      electron event which in dependence on pH may consist of two one-electron steps.
      It was demonstrated on the hydrolysis reaction of cyclocytidine hydrochloride to
      arabinosylcytosine at alkaline pH that the polarographic method may be used for
      the documentation of structural changes of pyrimidine nucleoside going on in the
      polarographic chamber.

PMID- 8289970
TI  - The effect of purine phosphonomethoxyalkyl derivatives on DNA synthesis in CHO
      Chinese hamster cells.
AB  - The inhibition of incorporation of 3H-thymidine and the changes of the rate of
      nascent DNA chain elongation were investigated in CHO Chinese hamster cells
      treated with (S)-(3-hydroxy-2-phosphonomethoxypropyl) (HPMP) and N-(2
      phosphonomethoxyethyl) (PME) derivatives of adenine (A), guanine (G) and 2,6
      diaminopurine (DAP). No direct correlation was observed in PME and HPMP
      derivatives between cytotoxicity, inhibition of 3H-thymidine incorporation and
      inhibition of nascent DNA chain elongation. The highest cytotoxicity and
      inhibition of DNA synthesis were caused by PMEG. The limited extent of inhibition
      of DNA elongation was encountered in the case of HPMPG and HPMPA. With PMEA, weak
      inhibition of elongation of DNA was observed only after a prolonged exposure (6
      h). None of the investigated drugs induced DNA breaks.

PMID- 8289971
TI  - Pre- and postirradiation hemopoietic effects of liposomal muramyl tripeptide
      phosphatidylethanolamine (MTP-PE) administered to C57Bl/6 mice before
      irradiation.
AB  - The effect of muramyl tripeptide (MTP-PE) encapsulated in liposomes
      (multilamellar vesicles, MLV) on hemopoiesis and hemopoietic recovery after
      sublethal single irradiation with a dose of 6 Gy was investigated. MTP-PE/MLV
      during 24 h after administration stimulated the monocyte/macrophage system and
      accelerated recovery from radiation-induced damage of hemopoiesis. The above
      reparative processes were accompanied by hyperplasia of granulocytes in the bone
      marrow on days 6-8 after irradiation, acceleration of erythropoiesis in the
      spleen and recovery of granulocyte count in the peripheral blood. The repair of
      thymic and splenic lymphoid tissues as well as recovery of the number of
      mononuclear cells in peripheral blood was not influenced by MTP-PE/MLV
      application.

PMID- 8289972
TI  - Selective cervical cytology screening: discriminant analysis approach.
AB  - Cervical cancer is one of the leading malignancies seen in Indian women. It has
      been well established that organized cervical cytology screening program is the
      mainstay for control of cervical cancer. It is not possible to carry out cervical
      cytology screening for masses in India due to paucity of human and financial
      resources. Hence there is a need for development of an alternate strategy to
      concentrate on women with high risk. In the present communication attempt was
      made to define a high risk group based on sociodemographic factors, viz. age,
      parity, education and clinical features. A total of 67,000 women were screened of
      which in 250 malignancy was detected. The rate of malignancy was observed to be
      high in women above 40 years (10.5/1000) with more than two children (6.1/1000)
      and in illiterate group (4.9/1000) as compared to women below 40 years, more than
      3 children and illiterate group. Similarly, the rates were higher in women with
      clinical diagnosis of cervical erosion which bled on touch, unhealthy cervix and
      suspicious looking cervix, malignancy rates were 17.1, 24.7, 263.2 (per 1000),
      respectively. An attempt was made to study the combined effect of all the six
      factors (sociodemographic and clinical) by employing the technique of linear
      discriminant analysis to find out the discrimination power between the normal and
      malignant women. Discriminant score thus obtained would help to classify the case
      for subjecting to cervical cytology. It was observed that the model containing
      sociodemographic and clinical variables was able to classify 69% of malignant
      cases correctly. When the clinical variables were dropped from the model, the
      sensitivity dropped to 65%. The above exercise indicated that based on the
      discriminant score even in the absence of facilities for clinical examination of
      women, it may be possible to identify women of high risk group for subjecting
      them to cervical cytology screening.

PMID- 8289973
TI  - Captopril in the diagnostic work-up of hypertensive patients with suspected renal
      artery stenosis.

PMID- 8289974
TI  - Disorders presenting as primary hyperaldosteronism.

PMID- 8289975
TI  - Phaeochromocytoma.

PMID- 8289976
TI  - Antihypertensive drug treatment. An appraisal of trials.

PMID- 8289977
TI  - Drug-induced hypertension.

PMID- 8289978
TI  - Non-pharmacological management of hypertension.

PMID- 8289979
TI  - The older hypertensive. Assessment and treatment.
AB  - A meta-analysis is presented of 8 therapeutic trials in elderly hypertensive
      patients. In an intention-to-treat analysis, cardiovascular mortality was
      decreased on average by 22% (95% confidence interval ranging from -32% to -10%).
      This decrease was explained by both a reduction in coronary mortality by 26% (
      40% to -9%) and in cerebrovascular mortality by 33% (-50% to -9%). The
      effectiveness of therapy in terms of reducing cardiovascular mortality is not
      established with confidence in those trials where the diastolic blood pressure at
      randomization is below 95 mmHg or in the patients above 75 years of age. A goal
      blood pressure is not definitively established, but a reduction of the systolic
      blood pressure to about 150 mmHg may be optimal. Extrapolation of the trial
      results to the elderly population with systolo-diastolic hypertension at large
      seems acceptable for the western population, but may be premature for the Asian
      and African elderly. Beta-blockers and especially diuretics are recommended as
      first-line drugs in elderly patients with symptomless, uncomplicated
      hypertension, since the effectiveness of other drugs in reducing morbidity and
      mortality is not yet established. Recommendation for treatment of symptomless
      patients with isolated systolic hypertension may be premature. The ongoing Syst
      Eur and Syst-Chin trials may provide further information.

PMID- 8289981
TI  - Hereditary nephrogenic diabetes insipidus and bilateral nonobstructive
      hydronephrosis.
AB  - We describe 2 cases of hereditary nephrogenic diabetes insipidus with massive
      bilateral dilatation of the urinary tract without any organic obstruction. A
      review of the literature revealed that dilatation of the urinary tract was
      present in 67% of the reported cases of nephrogenic diabetes insipidus which
      included a description of the urinary tract. This strong association between
      hereditary nephrogenic diabetes insipidus and nonobstructive hydronephrosis
      suggests a cause-and-effect relationship in which polyuria is responsible for the
      hydronephrosis.

PMID- 8289980
TI  - The pathogenic role of immunoglobulin A polymers in immunoglobulin A nephropathy.
AB  - Circumstantial evidence that pIgA has a key role in glomerular injury of IgAN is
      now strong. Although the answers to the questions posed in this review are
      necessarily incomplete, they do indicate that (1) pIgA is a major component of
      mesangial IgA. (2) circulating pIgA is increased and this pIgA is particularly
      enhanced during acute hematuric relapses of IgAN. As well as true J-chain
      positive pIgA, other macromolecular IgA species may circulate, including CIC,
      rheumatoid factors and complexes with fibronectin. (3) pIgA appears not to be
      derived from the mucosal lamina propria and may originate in the marrow and/or
      tonsil which may be unduly stimulated as a result of impaired oral tolerance. (4)
      Abnormalities of IgA production control are several, including genetic and
      cellular influences. Little is yet known about abnormalities specific for pIgA,
      although antigen-driven pIgA responses appear exaggerated and prolonged. In
      addition, pIgA enhancement may be due to activation of polyclonal antigen
      independent antibody production of low affinity. (5) There is some evidence that
      pIgA has an enhanced capacity to bind to mesangial cells and induce injury
      compared to mIgA. (6) As yet, it is unclear whether pIgA has particular effects
      on mesangial cell activity and the induction of progressive injury. While steady
      progress continues in the understanding of the role of pIgA in the
      immunopathogenesis of IgAN, the design of therapeutic strategies based on such
      understanding still remains a considerable way off.

PMID- 8289982
TI  - Prevalence of lupus anticoagulant and anticardiolipin antibodies in haemodialysis
      patients.
AB  - It has been suggested that a high prevalence of anticardiolipin antibody and
      lupus anticoagulant in haemodialysis patients may be a feature of dialysis
      membrane bioincompatibility. Previously published reports have given a prevalence
      of approximately 30% for IgG-anticardiolipin and 22-30% for the lupus
      anticoagulant in a population of haemodialysis patients, with a prevalence of 48%
      for IgG-anticardiolipin in a subgroup of patients dialysed with cuprophane
      membranes. The aim of this study was to analyse the prevalence of IgG- and IgM
      anticardiolipin antibodies, and also the lupus anticoagulant in a population of
      haemodialysis patients dialysed exclusively with cuprophane membranes. Forty-two
      patients on hospital-based haemodialysis were studied. Two patients (4.8%) had
      IgG-anticardiolipin, and 7 (16.7%) had IgM-anticardiolipin. No patients were
      positive for both IgG- and IgM-anticardiolipin. All positive results were of
      'low' or 'medium' positive titres. In the patients with positive results for
      anticardiolipin there were no documented episodes of thrombotic events. In the
      group studied there were no patients positive for the lupus anticoagulant. We
      conclude that the presence of anticardiolipin antibodies or lupus anticoagulant
      is rare in this population of haemodialysis patients and they are not a feature
      of membrane bioincompatibility.

PMID- 8289983
TI  - Flow cytometric analysis of hematuria using fluorescent antihemoglobin antibody.
AB  - To identify the morphological changes of urinary erythrocytes in hematuria
      objectively, flow cytometrical analysis of fluorescence-labeled erythrocytes was
      performed. Fifty-one fresh urine samples from 33 hematuric patients (16 with
      glomerulonephritis and 17 with urological disease) were obtained. Urine
      erythrocytes were stained with FITC-labeled antihemoglobin antibody, and
      distinguished from other particles with similar size. Forward scattered light
      intensity (FW-SC) was used as an indicator of red cell size and right
      orthogonally scattered light intensity (RT-SC) divided by forward scattering (RT
      SC/FW-SC) was used as a marker of cell surface irregularity. The size of
      erythrocytes expressed by FW-SC was significantly smaller in glomerulonephritic
      hematuria (101.6 +/- 41.8) than that in urological hematuria (123.5 +/- 44.7). RT
      SC/FW-SC was smaller in urological hematuria (1.22 +/- 0.18) in comparison with
      glomerulonephritic hematuria (1.33 +/- 0.12). These results suggest that
      erythrocytes in glomerulonephritic hematuria had smaller size and more complex
      surface structure in comparison with urological hematuria. When cutoff was set at
      110 of FW-SC for the criteria of glomerulonephritic erythrocytes, a correct
      diagnosis was made in 73.3% (22/30) of glomerulonephritic hematuria and in 76.2%
      (16/21) of nonglomerular hematuria. We clarified more complex morphological
      changes of glomerulonephritic urinary erythrocytes objectively.

PMID- 8289984
TI  - Renal hemodynamics in patients with cirrhosis: relationship with ascites and
      liver failure.
AB  - In patients with cirrhosis and ascites decreased renal blood flow might be
      related to the severity of liver disease but the relationship between the
      severity of cirrhosis and renal perfusion has not yet been established. Thus we
      measured renal, systemic and splanchnic hemodynamics in 63 patients with ascites
      and in 28 without ascites. When compared to patients without ascites, patients
      with ascites had lower renal blood flow (1,170 +/- 100 vs. 935 +/- 55 ml/min/1.73
      m2; mean +/- SEM, p < 0.05) and renal perfusion pressure (78 +/- 2 vs. 72 +/- 1
      mm Hg, p < 0.05 and higher inferior vena cava pressure (6.5 +/- 0.7 vs. 10.7 +/-
      0.7 mm Hg, p < 0.05). Patients with ascites had significantly higher serum
      bilirubin concentrations, hepatic venous pressure gradient and lower serum
      albumin concentrations, indocyanine green (ICG) extraction than patients without
      ascites. Renal vascular resistance, glomerular filtration rate, mean arterial
      pressure, cardiac index and systemic vascular resistance were not significantly
      different between the two groups. By multiple regression analysis no significant
      correlation was found between liver tests (i.e., prothrombin time, serum
      bilirubin and albumin concentrations, ICG extraction), hepatic venous pressure
      gradient, cardiac index and systemic vascular resistance on the one hand and
      renal blood flow on the other. No significant correlation was found between
      glomerular filtration rate and liver tests. In conclusion, in patients with
      cirrhosis and ascites, renal hypoperfusion is not related to the severity of
      liver disease.

PMID- 8289985
TI  - Vitamin D therapy modulates cytokine secretion in patients with renal failure.
AB  - In studies in vitro calcitriol (1,25-dihydroxyvitamin D3) inhibits lymphocyte
      proliferation and modulates several monocyte functions, including the secretion
      of prostaglandins and monokines. However its effects on monokine production in
      vivo are not known. Therefore we studied the secretion of interleukin (IL)-1, IL
      6 and tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMC)
      from 7 patients on periodic hemodialysis, before and after oral treatment with
      calcitriol (0.5 microgram daily) for 1 month. Calcitriol therapy resulted in
      significant increases in the phorbol myristate acetate (PMA)-induced secretion of
      IL-1 and IL-6 (p = 0.04 and 0.03, respectively). This was a transient effect,
      observable by day 7 of therapy, but no longer evident by day 30. However,
      calcitriol induced a progressive reduction of TNF secretion (down to 53% of
      control values by day 30, p = 0.02). There were no correlations between the
      individual changes in calcium/PTH and cytokine release. These results show that
      doses of calcitriol within the therapeutic range induce marked changes in
      cytokine secretion by PBMC from uremic patients.

PMID- 8289986
TI  - Oral calcium effectively reduces parathyroid hormone levels in hemodialysis
      patients: a randomized double-blind placebo-controlled study.
AB  - The objective of this study was to elucidate the effect of oral calcium
      supplement upon the severity of secondary hyperparathyroidism and
      hyperphosphatemia in patients undergoing hemodialysis. Twenty-three accepted to
      participate and were randomly allocated to receive in a double-blind manner
      either 2 g elemental calcium per day (n = 12) or placebo (n = 11) for 6 months.
      Three patients dropped out leaving 10 patients in each group. In the calcium
      group serum ionized calcium increased significantly during the 1st month from
      1.15 +/- 0.02 to 1.29 +/- 0.04 mmol/l (mean +/- SE) and was then stabilized at an
      average of 1.26 +/- 0.02 mmol/l for the remaining 5 months. Serum intact
      parathyroid hormone (PTH) decreased in average by 54% within the 1st month and
      remained at that level for the following months. Hyperphosphatemia remained
      stable throughout. On the contrary, in the placebo group, serum concentrations of
      ionized calcium and intact PTH remained unchanged, while serum phosphate
      increased significantly. The present study demonstrates that oral calcium reduces
      secondary hyperparathyroidism and prevents the progression of hyperphosphatemia
      in patients undergoing hemodialysis.

PMID- 8289987
TI  - Hypouricemia due to increased tubular secretion of urate in children with Amanita
      phalloides poisoning.
AB  - The tubular transport of urate was studied in 20 children poisoned with Amanita
      phalloides and in control group. The aim of this study was to investigate the
      cause of repeatedly observed episodes of hypouricemia in patients after A.
      phalloides poisoning. A significant negative correlation between serum uric acid
      concentration and fractional excretion of urate in poisoned and control groups (r
      = 0.73, p < 0.001) was found. The results of pyrazinamide and probenecid tests
      performed in patients after A. phalloides poisoning indicated that
      hyperuricosuria was most likely due to an increment in renal tubular urate
      secretion, and not due to decreased presecretory and postsecretory reabsorption
      of uric acid. These findings indicate that hypouricemia found after A. phalloides
      poisoning in children is of renal origin due to an increase in tubular urate
      secretion.

PMID- 8289988
TI  - Renal abnormalities in leprosy.
AB  - We have evaluated laboratory and clinical manifestations of renal disease in 96
      patients with leprosy, looking for a sensitive and early marker for detection and
      possibly follow-up of nephropathy in these patients. Microscopic hematuria was
      observed in 21.9% of the cases (with dysmorphic erythrocytes in 71.4% of them).
      Abnormal microalbuminuria and urinary beta 2-microglobulin were found in 15.8 and
      19.8% of the cases, respectively. We have observed a high frequency of hematuria,
      abnormal microalbuminuria and elevation of urinary beta 2-microglobulin in these
      patients still with normal serum creatinine.

PMID- 8289989
TI  - In vitro approach to 'uremic cardiomyopathy'.
AB  - Cardiovascular complications determine the prognosis of patients with chronic
      renal failure. The contribution of compounds retained during uremia to specific
      myocardial lesions is controversial. We investigated the contractility of
      spontaneously beating mouse cardiac myocytes in culture under perfusion with sera
      derived from patients on maintenance hemodialysis and test solutions containing
      possible toxins. Cellular contractility under defined environmental conditions is
      determined by a computer-assisted digital image analysis. 'Uremic sera',
      creatinine, urea, and combinations of these compounds reduce inotropy of the
      cultured heart cells, induce arrhythmias or asynchronies in a concentration
      dependent manner. We propose the myocyte perfusion technique as an in vitro
      approach to identify cardiotoxins in the body fluids of chronically uremic
      patients.

PMID- 8289990
TI  - Conjugated diene fatty acids in patients with chronic renal failure: evidence of
      increased lipid peroxidation?
AB  - Conjugated diene fatty acids (CDFA) were evaluated by second derivative
      spectrophotometry in the plasma and adipose tissue of 42 chronic renal failure
      (CFR) patients in conservative treatment, 40 patients treated by hemodialysis
      (HD) with cuprophane, cellulose acetate or hemophan, 29 treated by
      hemodiafiltration (HDF) with polysulfone, polyacrylonitrile or polyamide, and 28
      healthy controls. Plasma CDFA were also evaluated at the beginning, at 30 min and
      at the end of the dialytic session. CDFA were unchanged in CRF patients with
      creatinine clearance (Ccr) > 10 ml/min respect to the controls, CRF patients with
      Ccr < 10 ml/min showed a higher level of CDFA both in plasma and adipose tissue
      (p < 0.02). HD patients showed values similar to those of the control group. The
      lowest level of CDFA was found in HDF patients (p < 0.01 for plasma, p < 0.05 for
      adipose tissue versus both control and any other group). A significant
      relationship between plasma and adipose tissue CDFA was found in all groups. In
      the group of CRF patients with Ccr < 10 ml/min, females exhibited a higher level
      of CDFA both in plasma and adipose tissue. No significant change was found during
      dialytic session, independently from the membrane used. CDFA are not only primary
      products of lipid peroxidation, but also have a dietary origin, primarily from
      dairy products. Taking into account the reduced dietary intake, the increase in
      end-stage CRF may be due to an enhanced oxidative stress and/or to abnormalities
      in CDFA metabolism. Uremic patients, particularly in the predialytic stage,
      should be considered at risk for increased oxidative stress. HDF treatment better
      corrects the abnormality compared to conventional HD.

PMID- 8289991
TI  - Plasma concentration profiles of simvastatin 3-hydroxy-3-methyl-glutaryl-coenzyme
      A reductase inhibitory activity in kidney transplant recipients with and without
      ciclosporin.
AB  - A few cases of severe rhabdomyolysis have been reported in heart transplant
      recipients treated simultaneously with ciclosporin (CS) and the 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin. When
      measured, plasma lovastatin HMG-CoA reductase inhibitor concentrations in these
      patients were higher than expected. This prompted us to study the plasma
      concentration profiles of simvastatin HMG-CoA reductase inhibitory activity after
      a single dose of simvastatin in kidney transplant recipients. Five patients
      treated with CS, azathioprine and prednisolone (CS patients) were compared to 5
      patients treated with azathioprine and prednisolone (non-CS patients). The
      concentration curves had similar shapes but the mean area under the curve/24 h
      was almost 3 times higher (p = 0.047) and the mean peak concentration was twice
      as high in CS patients (p = 0.028). These results suggest a difference in the
      disposition of simvastatin in CS patients as compared to non-CS patients.
      Simvastatin should be administered in a reduced dosage to CS patients.

PMID- 8289992
TI  - Effects of erythropoietin on trace elements in patients with chronic renal
      failure undergoing hemodialysis.
AB  - We examined the relationship between recombinant human erythropoietin (rHuEPO)
      therapy and serum levels of the trace elements aluminum, silicon, zinc, nickel,
      and manganese in 55 patients undergoing chronic hemodialysis (HD) in whom rHuEPO
      (for 12 weeks) was effective in reducing anemia, and in 55 patients undergoing HD
      without rHuEPO treatment. In the rHuEPO group, serum Al level was significantly
      decreased and Si level showed a tendency to decrease. Zn, Ni, and Mn levels,
      however, were significantly increased.

PMID- 8289993
TI  - Amelioration of antioxidant enzyme suppression and proteinuria in cyclosporin
      treated puromycin nephrosis.
AB  - The effect of cyclosporin (CS) on intrinsic glomerular level of antioxidants in
      puromycin aminonucleoside (PAN) nephrosis was examined. A single intravenous dose
      of PAN (50 mg/kg body weight) given to Sprague-Dawley rats resulted in marked
      proteinuria. Ten days after PAN injection, the rats were treated with daily
      intraperitoneal injection of CS (10 mg/kg body weight/day) for 10 days. PAN
      treated rats without CS treatment (PAN rats) had significantly lower activities
      of glomerular superoxide dismutase (SOD) and catalase (CAT) than normal rats (p <
      0.05, respectively). When compared with PAN rats, CS-treated PAN rats had
      significantly less proteinuria and higher activities of glomerular SOD and CAT (p
      < 0.01 and p < 0.05, respectively). Significant elevation of glomerular
      malondialdehyde (MDA) level characteristic of PAN rats was absent in CS-treated
      PAN rats. Moreover, segmental sclerosis with capsular adhesion, hyalinosis,
      epithelial cell foot process fusion and microvillous transformation seen in PAN
      rats were apparently attenuated in CS-treated PAN rats. When compared with normal
      rats, rats receiving CS only had a significantly higher CAT activity and MDA
      level (p < 0.01 and p < 0.05, respectively). Assessment of glomerular reduced
      glutathione revealed no significant differences among PAN rats, CS-treated PAN
      rats, normal rats, and rats receiving only CS. These data indicate that
      glomerular antioxidant enzyme activities are modulated by CS.

PMID- 8289994
TI  - Effects of an angiotensin II receptor antagonist on the progression of renal
      failure in hyperlipidemic Imai rats.
AB  - This study was undertaken to determine the role of angiotensin II (AII) in the
      development of glomerulosclerosis, using an AII receptor antagonist in an animal
      model of hyperlipidemia. Hyperlipidemic Imai rats were employed because they
      spontaneously develop glomerulosclerosis; this is especially true in males. Group
      1 (n = 5) received no specific therapy. Group 2 (n = 5) was treated with
      enalapril at a dosage of 50 mg/l in drinking water starting at 6 weeks of age.
      Group 3 (n = 5) and group 4 (n = 6) were treated with the AII receptor antagonist
      DuP 753 at a respective dosage of 15 mg/l (low-dose DuP) and 150 mg/l (high-dose
      DuP) in drinking water. Body weight, blood pressure, urinary protein, serum
      albumin, cholesterol, BUN and serum creatinine were measured and compared among
      the groups from 12 to 24 weeks of age. Enalapril and high-dose DuP were almost
      equally effective in controlling systemic hypertension. Each treatment
      significantly reduced proteinuria (172 +/- 112 and 152 +/- 72 mg/kg/day at 24
      weeks) as compared with that in the controls (421 +/- 147 mg/kg/day; p < 0.05 and
      p < 0.01, respectively). Hypercholesterolemia also decreased (82 +/- 4 and 89 +/-
      6 mg/dl) as compared with that of the controls (141 +/- 48 mg/dl; both p < 0.05).
      Glomerulosclerosis index (SI) was significantly higher in the untreated control
      rats (55 +/- 26) than in the enalapril-treated rats (2 +/- 3; p < 0.005) and the
      high-dose-DuP-treated rats (6 +/- 6, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8289996
TI  - Effects of intravenous administration of recombinant human erythropoietin in rats
      subject to hemorrhagic shock.
AB  - The effects of recombinant human erythropoietin (rHuEPO) on survival and blood
      pressure in hypovolemic hemorrhagic shock in rats have been studied by
      intravenous administration. The hormone caused an increase in the time of
      survival compared to the group of rats without treatment (102 +/- 4.5 vs. 25 +/-
      4.5 min, p < 0.01, vehicle; 102 +/- 4.5 vs. 25 +/- 2 min, p < 0.01, saline
      solution) and an increase in the percentage of the surviving animals (5/7 after
      120 min vs. 0/7, p < 0.05). The animals treated showed an increase in mean
      arterial pressure that was not present in the control group. Through their data,
      the authors suggest the vasopressor effect of erythropoietin. Furthermore, from
      other studies done before, they hypothesize that the vasoactive ability of the
      hormone is endothelin mediated.

PMID- 8289995
TI  - Proton nuclear magnetic resonance spectroscopy of urine and plasma in renal
      transplantation follow-up.
AB  - Urine and plasma samples from 39 patients who underwent renal transplantation
      were analyzed by proton nuclear magnetic resonance (NMR) spectroscopy. The most
      relevant resonances for evaluating renal function after transplantation were
      those arising from citrate, trimethylamine-N-oxide (TMAO), alanine, and lactate
      when compared to creatinine. A resonance at 3.7 ppm was related to cyclosporine
      toxicity when associated with elevated levels of TMAO. The respective variations
      in these metabolites in urine could contribute to prognosis and diagnosis of
      renal function impairment related to cyclosporine toxicity or overdosage, or to
      rejection. Thus, NMR spectroscopy should improve the follow-up and management of
      renal transplantation patients.

PMID- 8289997
TI  - Loss of glomerular anionic sites and the development of albuminuria in rats with
      streptozotocin-induced diabetes.
AB  - Examination was made of changes in the anionic sites of the glomerular basement
      membrane (GBM) in rats with streptozotocin (STZ)-induced diabetes by the
      immersion method of polyethyleneimine (PEI). PEI particles in GBM of diabetic
      rats significantly decreased from the 1st through the 8th week. Urinary albumin
      excretion in diabetic rats significantly increased at the 2nd but not earlier
      week. Insulin treatment effectively prevented decrease in PEI particles in STZ
      injected rats. In rats with STZ-induced diabetes, initial renal alteration was
      disturbance of the charge barrier, followed by the development of albuminuria.
      Continued deterioration of anionic sites and possibly additional disturbance of
      size barrier were considered responsible for the development of albuminuria.
      Insulin treatment appears to prevent the loss of anionic sites of GBM.

PMID- 8289998
TI  - Increased pulmonary platelet sequestration due to infusion of cold saline during
      extracorporeal circulation.
AB  - We have previously documented that neutrophils (polymorphonuclear leukocytes)
      aggregate in the lungs 10-15 min after the start of dialysis. The aim of the
      present study was to investigate the corresponding platelet reaction and evaluate
      the effect of prewarmed priming solution on this reaction. The animals were
      divided into two groups, each consisting of 6 pigs. In group 1 the priming
      solution was prewarmed to 36-38 degrees C whereas it was maintained at room
      temperature in group 2. Platelets were selectively labelled with 111In-oxine. The
      activity over the lung was followed dynamically with a gamma camera and already
      after 2 min a significant difference in platelet sequestration showed between the
      groups. A significant increase in pulmonary vascular resistance was noted in
      group 2, but not in group 1. In conclusion, platelet aggregation occurs early on
      during dialysis in this model. The results also indicate that prewarming the
      priming solution attenuates the pulmonary platelet sequestration and also seems
      to decrease the changes in central hemodynamics.

PMID- 8289999
TI  - Increased plasma levels and effects of brain natriuretic peptide in experimental
      nephrosis.
AB  - Rat brain natriuretic peptide-45 (BNP-45) is a new cardiac hormone secreted into
      the circulation. In order to evaluate the pathophysiologic role of BNP in the
      nephrotic syndrome, we investigated the plasma levels and effects of BNP in
      adriamycin (ADR)-induced nephrotic rats. Plasma levels of BNP rose with time and
      more than doubled in 3 weeks after injection. Plasma levels of BNP correlated
      significantly with urinary protein excretion (UPrV) and urinary
      protein/creatinine ratio (UPrV/UcrV). When rat BNP-45 was injected as a bolus,
      hypotensive, diuretic, and natriuretic effects were completely abolished in
      nephrotic animals even at a high dose (2.0 nmol/kg), whereas the peptide produced
      marked UPrV with an increase in UPrV/UcrV. These results indicate that in ADR
      induced nephrosis, BNP secretion from the heart is increased. Remarkable
      resistance to some hemodynamic and renal effects, while prompt proteinuric
      effects of BNP, may contribute to the sodium and water retention and urinary
      protein characteristic of this disorder.

PMID- 8290000
TI  - Hypercalciuria and nephrocalcinosis, a feature of Wilson's disease.
AB  - Hypercalciuria and nephrocalcinosis are not uncommon in patients with Wilson's
      disease but have only once been reported as the presenting sign. We diagnosed
      Wilson's disease in a 17-year-old male patient 6 years after his first episode of
      gross hematuria and 2 years after detection of hypercalciuria and
      nephrocalcinosis. Therapy with penicillamine resulted only in a moderate
      reduction of urinary calcium excretion but oxalate excretion increased.

PMID- 8290001
TI  - Compressive myelopathy due to dialysis-associated amyloidosis.
AB  - A 66-year-old woman presented a spastic quadriparesis due to compression of the
      cervical cord 6 years after the beginning of chronic hemodialysis. Five years
      later, she developed a second episode of compressive myelopathy affecting the
      lumbar spine. On both occasions, surgical laminectomy with removal of
      fibroligamentous rings that compressed the cord led to a total recovery of the
      patient. Histological study demonstrated the presence of massive amyloid deposits
      in the surgically excised material.

PMID- 8290002
TI  - Granulocyte-monocyte colony-stimulating factor levels during hemodialysis-induced
      leukopenia.
AB  - Hemodialysis (HD), especially with cellulosic membranes, leads regularly to a
      transient but marked drop of peripheral neutrophils. Such neutropenia during the
      initial 10-30 min of HD is followed by a reincrease in granulocyte count up to a
      mild leukocytosis. Although this phenomenon accounts for the best documented side
      effect of HD, little is known about the underlying regulatory mechanisms.
      Therefore in this study the blood levels of granulocyte-macrophage colony
      stimulating factor (GM-CSF) were measured during HD. Previous investigations have
      demonstrated that GM-CSF plays the central role in controlling the homeoiostasis
      of leukocytes by up- and downregulation of proliferation and efflux of cells out
      of the maturation compartment within the bone marrow. Three patients with chronic
      renal failure underwent HD with cuprophane membranes. In all cases a significant
      drop of peripheral granulocytes occurred, but GM-CSF levels remained unchanged
      and were found in the normal range during the whole period of the treatment. It
      is therefore concluded that GM-CSF may not be significantly involved in the
      regulation of peripheral leukocytes during HD.

PMID- 8290003
TI  - Serum beta-2-microglobulin level and residual renal function in peritoneal
      dialysis.
AB  - In 32 noncirrhotic patients on peritoneal dialysis, mean serum beta 2
      microglobulin (s beta 2M) was 26.58 +/- 12.32 mg/l (9.7-63.5). We found a
      significant correlation between s beta 2M and serum creatinine (sCr; r = 0.760),
      blood urea nitrogen (BUN; r = 0.573), total creatinine and BUN clearance (r =
      0.623 and 0.599, respectively), 24-hour Kt/V (r = 0.638), glomerular filtration
      rate (r = 0.623), 24-hour urine output (r = 0.669), serum total protein (r =
      0.584) (p < 0.01 for all the above r values); beta 2M peritoneal clearance and
      mass transfer (r = 0.414 and 0.427, respectively; p < 0.05). Our data demonstrate
      and confirm the contribution of residual renal function in determining s beta 2M
      levels and it is seemingly more important than beta 2M peritoneal clearance.

PMID- 8290004
TI  - Limitation of kidney biopsy in detecting crescentic lesions in IgA nephropathy.

PMID- 8290005
TI  - Long-term effect of intravenous reinfusion of unmodified autogenous peritoneal
      fluid combined with hemodialysis in a patient with dialysis-related ascites.

PMID- 8290006
TI  - Interaction of josamycin with cyclosporin A.

PMID- 8290007
TI  - Does interaction between omeprazole and cyclosporin exist?

PMID- 8290008
TI  - Alport syndrome with type I membranoproliferative glomerulonephritis.

PMID- 8290009
TI  - Accumulated end products participate in glucose intolerance and insulin
      resistance in uremia.

PMID- 8290010
TI  - Recklinghausen's neurofibromatosis associated with membranous nephropathy.

PMID- 8290011
TI  - Campylobacter fetus subspecies fetus peritonitis in continuous ambulatory
      peritoneal dialysis.

PMID- 8290012
TI  - Sialic acid is a predictor of cardiovascular complications in renal
      transplantation recipients.

PMID- 8290013
TI  - Spontaneous bilateral rupture of the Achilles tendons in a renal transplant
      recipient.

PMID- 8290014
TI  - Hepatitis-associated improvement of anemia in an anephric patient without
      elevation of serum erythropoietin level.

PMID- 8290015
TI  - Effect of human recombinant erythropoietin treatment on erythrocyte delta
      aminolevulinic acid dehydratase in patients on maintenance hemodialysis.

PMID- 8290016
TI  - Anaphylactoid reactions, angiotensin-converting enzyme inhibitors and
      extracorporeal hemotherapy.

PMID- 8290017
TI  - Real cause of high level of urinary beta 2-microglobulin after renal
      transplantation.

PMID- 8290018
TI  - Is the intracellular calcium-mediated pathway involved in erythropoietin-induced
      hypertension?

PMID- 8290019
TI  - The contribution of the anterior thalamic nuclei to anterograde amnesia.
AB  - This paper first reviews the anatomical, pathological, and neuropsychological
      evidence implicating the anterior thalamic nuclei in memory processes. It is
      concluded that there is much indirect evidence indicating that anterior thalamic
      dysfunction is an important factor in anterograde amnesia. More direct evidence
      for the involvement of the anterior thalamic nuclei in memory processes emerges
      from two experiments with rats that examined performance of a spatial test of
      working memory, delayed nonmatching-to-position. The first study revealed that
      neurotoxic lesions of the anterior thalamic nuclei and radiofrequency lesions of
      the fornix both produce equivalent performance deficits. In contrast, lesions of
      the mamillary bodies were without effect. A second study showed that lesions of
      the fornix and removal of the hippocampus produced very similar deficits. These
      data indicate that while the involvement of the anterior thalamic nuclei in
      certain memory functions depends on inputs from the hippocampus, this involvement
      need not depend on indirect afferents via the mamillary bodies.

PMID- 8290020
TI  - Hippocampectomized monkeys can remember one place but not two.
AB  - In an earlier study by Parkinson et al. (J. Neurosci. 8, 4159-4167, 1988),
      hippocampectomized monkeys were found to be impaired on a task in which they were
      required to remember the spatial positions of trial-unique objects overlying two
      of the wells in a three-well test tray. There were two types of trial in the
      task. One type (object-place) required memory for the conjunction of object
      quality and object location, whereas the other (place only) required memory only
      for the location of the objects, i.e. independent of object quality. The
      hippocampectomized monkeys performed at near chance levels on both types of
      trials. The present study sought to determine whether the poor performance of the
      hippocampectomized monkeys on the place-only trials, which closely resembled
      spatial delayed response (an ability that is unaffected by hippocampectomy when
      similarly short delays are used), could have been due to interference from the
      simultaneous training they had received on the object-place trials. To this end,
      we examined the effect of hippocampal removals on performance of the "place-only"
      trial type when that was the only training given. The hippocampectomized monkeys
      in the present study were found to be just as severely impaired as those in the
      earlier study, thus ruling out the possible explanation outlined above. Since
      performance on this modified version of spatial delayed response, unlike
      performance on the classical version with the same delay, is critically dependent
      on the hippocampus, it appears that monkeys with hippocampectomy can remember one
      place after a short delay but not two.

PMID- 8290021
TI  - Long-term potentiation of hippocampal afferents and efferents to prefrontal
      cortex: implications for associative learning.
AB  - It has been proposed that the physical substrate of memory resides in alterations
      of the strengths or weights of modifiable synaptic connections. In recent years,
      the hypothesis that the mechanisms underlying a particular form of synaptic
      plasticity, known as long-term potentiation, or LTP, are activated during
      learning and may actually subserve the formation of associative memories, has
      gained much empirical support. This paper reviews experimental studies suggesting
      that changes in synapse physiology and chemistry are involved in the formation of
      neural associative representation in hippocampal networks during classical
      conditioning. Recent experiments investigating LTP and learning-induced synaptic
      changes at hippocampal outputs to the prefrontal cortex are reported. The results
      provide a working framework within which the dynamics of information storage in
      hippocampal and prefrontal cortical networks is profiled.

PMID- 8290022
TI  - Additive effects of forgetting and fornix transfection in the temporal gradient
      of retrograde amnesia.
AB  - Nine Rhesus monkeys (Macaca mulatta) learned to discriminate among 320 complex
      naturalistic scenes (Set A) for food reward. Six months later they learned to
      discriminate among a further 192 scenes (Set B). Immediately after learning Set B
      the animals were given a preoperative retention test of both sets, consisting of
      a single trial with every scene they had learned. Three monkeys were then
      operated upon to transect the fornix, the other six forming an unoperated control
      group. Two weeks after operation the scenes were presented once each in a
      postoperative retention test. The animals with fornix transection showed
      significantly poorer memory than the control animals at the postoperative
      retention test. Furthermore, within the fornix-transected animals' performance,
      postoperative amnesia for Set B was more marked than amnesia for Set A, by
      comparison with the animals' own preoperative retention of the two sets. However,
      a similar pattern of performance was also seen within the control animals'
      results, in that they forgot more of Set B than of Set A in the interval between
      the preoperative and postoperative retention tests. There was no significant
      difference between the groups in the gradient of forgetting, defined as the
      difference between forgetting of Set B and forgetting of Set A in the interval
      between the preoperative and postoperative retention tests. These results give no
      support to the idea that the severity of retrograde amnesia is graded as a
      function of the remoteness of the memory at the onset of amnesia, and they give
      some indication of possible reasons why the impression of such a gradient is
      frequently reported clinically.

PMID- 8290023
TI  - Retrieval of a face discrimination during suppression of monkey temporal cortex
      with cold.
AB  - Cells in the monkey temporal cortex that respond selectively to faces suggest
      that monkeys might have a brain structure similar to that in humans where lesions
      produce prosopagnosia, but effects of lesions on retrieval of face
      discriminations have been ambiguous in monkeys. It is possible that the stimuli
      in the monkey experiments were contaminated with non-face elements that could be
      discriminated by other parts of the visual system. In this experiment we modified
      the image of a monkey face creating two faces that were identical except for
      their internal features. We trained monkeys to discriminate these faces and then
      reversibly suppressed the inferotemporal cortex with cold and tested their
      ability to recall them. Cooling the temporal cortex produced a severe impairment
      in retrieval of the discrimination that remained constant across six 40-trial
      replications.

PMID- 8290024
TI  - Comparative effects of excitotoxic lesions of the hippocampus and septum/diagonal
      band on conditional visual discrimination and spatial learning.
AB  - Several experiments compared the effects of excitotoxic lesions of the
      septal/vertical limb nuclei of the diagonal band of Broca (VDB) complex with
      those of the hippocampus (sparing the subiculum) on different forms of visual
      discrimination learning. The septal/VDB lesions, which produced significant
      reductions in choline acetyltransferase activity in the hippocampus and the
      cingulate cortex, impaired acquisition of a conditional visual discrimination in
      an operant chamber, while the hippocampal lesion had no effect, unless there was
      a delay interposed between the discriminative stimulus and the response. Neither
      lesion affected simple visual or spatial discrimination or reversal learning,
      also carried out in operant chambers, but both significantly impaired the
      acquisition and retention of a spatial navigation task (Morris water maze), with
      the septal/VDB lesions again producing greater deficits than the hippocampal
      lesions. Possible explanations for this surprising result are discussed and it is
      concluded that; (1) additional cholinergic de-afferentation of the cingulate
      cortex produced by the septal/VDB lesion is of functional significance; (2) this
      may lead to deficits in conditional rule learning, which can contribute to
      spatial navigation performance under certain circumstances; and (3) the
      contribution of septal-hippocampal cholinergic projections to spatial learning is
      in need of re-appraisal.

PMID- 8290025
TI  - Configurational encoding of complex visual forms by single neurons of monkey
      temporal cortex.
AB  - Single neurons in the anterior inferior temporal (IT) cortex respond to complex
      visual stimuli. Here we examined whether the stimulus-selectivity of the anterior
      IT neurons was determined solely on the basis of the geometric similarity of
      object forms, or was modifiable through visual experiences in adulthood. We
      trained Japanese monkeys (Macaca fuscata) in the visual delayed matching-to
      sample task or visual stimulus-stimulus association task. Computer-generated
      visual forms, fractal patterns or Fourier descriptors, were used as stimuli.
      Single-unit recording from these trained monkeys showed that the stimulus
      selectivity of neurons in the anterior IT cortex could be acquired according to
      the requirements of memory tasks. The results indicate that the neural
      representation of complex visual objects is dynamically altered through both
      tuning and association processes. We discuss these neurophysiological findings in
      relation to neuropsychological investigations of ablation effects in the primate.

PMID- 8290026
TI  - The participation of cholinergic systems of the nucleus accumbens in the
      differentiation of acoustic signals in dogs.
AB  - The influence of microinjections of the choline agonist, (carbacholine 0.05-0.1
      microgram), into the nucleus accumbens (Acc) of the right and left hemispheres on
      the realization of an instrumental defense reflex associated with the maintenance
      of a specific posture, and on the differentiation of acoustic signals in a
      defense situation, was studied in chronic experiments in five dogs. It was
      demonstrated that the injection of fairly small doses of carbacholine (CbCh) into
      the Acc of the left and right hemispheres improves the differentiation of
      acoustic signals in the defense situation. The introduction of fairly small doses
      of CbCh also improves the values of the criteria of the execution of the
      instrumental defense reaction associated with the maintenance of a specific
      posture. The changes observed are prolonged in character. Analysis of the motoric
      components of the instrumental responses made it possible to evaluate objectively
      the contribution of the motor and sensory mechanisms to those changes which were
      elicited by the microinjections of CbCh into the Acc, and to reach conclusion
      regarding an important role of the cholinergic system of the nucleus accumbens in
      sensory processes associated with the initiation and realization of instrumental
      responses to defense and differential signals, and especially in the regulation
      of attention to significant stimuli.

PMID- 8290027
TI  - The influence of chronic activation and blockade of the dopamine- and
      enkephalinergic systems of the neostriatum on conditioned reflex behavior and
      dopamine metabolism in the rat nigrostriatal system.
AB  - The effects of daily injections, over the course of 14 days, of 45 micrograms of
      phenamine, 5 micrograms of haloperidol and naloxone, 15 micrograms of leu
      enkephalin and its analog, a tetrapeptide, into the rostral neostriatum have been
      studied. The chronic stimulation of the dopaminergic system of the striatum
      induced facilitation of the realization of an active avoidance conditioned
      reflex, and stimulated exploratory stereotypy, while its blockade led to
      suppression of conditioned reflex activity against the background of a clearcut
      rigid akinetic syndrome. The microinjections of leu-enkephalin and naloxone did
      not substantially alter the behavior, but the injection of the tetrapeptide was
      accompanied by changes in behavior, with symptoms of catalepsy and hyperkinesia.
      Injections of phenamine and haloperidol were accompanied by a decrease in the
      content of dopamine in the striatum and an increase in the level of DOPAC; the
      injections of enkephalin and naloxone induced changes of the reverse order. The
      possible causes of the noncorrespondence of the behavioral and neurochemical
      shifts in the presence of a direct chronic pharmacological action on the mediator
      of the neostriatum.

PMID- 8290028
TI  - The temporal organization of the correlational association of neurons of the cat
      motor cortex.
AB  - The multineuronal activity was recorded in cats with a developed conditioned food
      procuring reflex to time. Cross-correlation histograms were plotted on the basis
      of the impulse activity of individual neurons isolated from the multineuronal
      activity, and an analysis was made of the distribution in real time of the
      impulses constituting the peaks on these histograms. The secondary analysis of
      the histograms made it possible to identify the dynamics of the changes in the
      functional connections between neurons over the course of the phase of active
      waiting on the basis of the distribution of coupled impulses. It was demonstrated
      in simultaneously recorded neuronal pairs that the concentration of coupled
      impulses was observed at various moments in time. Neuronal pairs, the
      concentration of whose coupled impulses is found towards the end of the
      conditioned reflex interval, were noted; this is regarded as the manifestation of
      a conditioned reflex reaction at the level of interneuronal interaction.

PMID- 8290029
TI  - The spontaneous activity of hippocampal neurons during the modulation of theta
      rhythm by cholinergic substances.
AB  - A statistical analysis of the baseline activity of neurons, recorded
      intracellularly in the hippocampus of awake, nonimmobilized rabbits in three
      states, control and during the systemic administration of eserine and
      scopolamine, was carried out. Neurons of the hippocampus were additionally tested
      in a similar manner following the chronic basal undercutting of the septum,
      removing stem influences. The cholinergic substances regulate the number of
      neurons of the hippocampus having theta modulation and the degree of its
      stability, but do not influence its frequency. When the cholinergic theta rhythm
      is activated, regularization of the activity takes place with the suppression of
      delta modulation and of "complex spikes"; its blockade is accompanied by the
      opposite changes. Both substances stably alter the level of the baseline
      frequency of discharges of the majority of neurons, although the total average
      frequency remains constant. Regression analysis shows the predominance of a
      decrease in the activity in high-frequency (> 25 spikes/sec) and an increase in
      the low-frequency (< 25 spikes/sec) neurons during the effect of both substances.
      The constancy of the total average frequency and the unidirectionality of the
      shifts in the level of discharges of the neurons during the intensification
      (eserine) and blockade (scopolamine) of the cholinergic component of the theta
      rhythm points to the fact that the cholinergic septal input directly influences
      mainly the structure but not the level of the activity of the hippocampal
      neurons.

PMID- 8290030
TI  - Neuronal activity in suspension transplants of the neocortex.
AB  - The characteristics of suspension (ST) and tissue (TT) transplants of the
      embryonal neocortex, transplanted into adult rats into the neocortical region of
      the representation of the vibrissae, were compared. The degree of taking of the
      ST and the TT did not differ significantly (89.5 and 95%, respectively).
      Transplants completely isolated from the brain were not found in the ST on the
      basis of histological and electrophysiological indices. The reactivity of ST
      neurons during electrical stimulation of the brain structures of the recipient
      and sensory stimulation, like the latent periods of the on-responses, did not
      differ significantly in the ST and the TT; however, the per cent of neurons
      responding with on-responses, was nearly twice as low in the ST as in the TT. At
      the same time, there were substantially more neurons in the ST responding to
      tactile stimulation with inhibition of discharges. It is hypothesized that the
      disruption in the primary cytoarchitectonics of the ST which takes place
      inevitably in the preparation of the suspensions is a cause of the differences
      indicated between the ST and the TT.

PMID- 8290031
TI  - Does the destruction of catecholaminergic neurons in newborn rats influence the
      modulator function of the cholinergic system?
AB  - The influence of the destruction of the catecholaminergic (CA) system on the
      reactions of neurons of the somatosensory zone of the cortex elicited by
      stimulation of the sciatic nerve, and on the features of the modulation of these
      reactions following the stimulation of the region of the basal nuclei (source of
      cholinergic innervation of the neocortex) and the microiontophoretic application
      of acetylcholine (ACh), was investigated in mongrel infant rats, 21-31 days of
      age. It was demonstrated that destruction of the CA system in newborn rats
      increases the reactivity of neurons somatosensory cortex to sensory stimulation,
      has no influence on the modulating effect of the cholinergic system, of the
      forebrain, and leads to intensification of the modulating influence of applied
      ACh [2].

PMID- 8290032
TI  - The influence of ablation of the sensorimotor area of the cortex on the spectral
      characteristics of the species-specific of the domestic cat.

PMID- 8290033
TI  - Disturbance of neuroendocrine regulation of sexual behavior of male rats with
      streptozotocin diabetes.
AB  - Sexual behavior is a constituent of the reproductive function of the organism. In
      sexually mature individuals the synchronization of the level of sexual activity
      with the reaction of the hypothalamo-hypophyseo-gonadal system to the relevant
      environmental stimuli is a necessary condition for the preservation of the
      species. In this context, the study of the neuroendocrine mechanisms shaping a
      specific level of activity of sexual behavior is an important problem for
      investigators. The dependence of the level of sexual activity on the integrity of
      certain CNS structures (first of all, the olfactory bulbs, amygdala,
      hypothalamus, and hypophysis) has been established. It has been demonstrated that
      label sex steroids accumulate selectively, and the regulation of the function of
      the gonads on the negative feedback principle is also accomplished in these
      regions precisely. In addition to the participation of the sex steroids in the
      formation of a specific level of sexual activity, an important role has been
      established at the present time for luliberin (LHRH) producing system and the
      neurotransmitters. The stability of the functioning of the reproductive system
      depends on a multiplicity of factors of the internal and external milieu. Serious
      disturbances in its function are associated with the alteration in carbohydrate
      homeostasis underlying a disease such as diabetes mellitus. This is manifested in
      a reduction in the weight of the accessory sex glands, steroidogenic activity and
      spermatogenesis, in a change in the secretion of gonadotropins, as well as in a
      diminution of fertility and sexual behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290034
TI  - The topical organization of projections of the nuclei of the amygdaloid body,
      ventral tegmental field, and substantia nigra in the striopallidum of the cat
      brain.

PMID- 8290035
TI  - The ultrastructure of axospinous synapses during functional reorganizations.

PMID- 8290036
TI  - Correction of a disturbance in visual recognition in monkeys with the aid of an
      antioxidant.
AB  - The influence of an effective antioxidant, oxymethacil, was studied in a model of
      the disruption of visual recognition induced by the antidepressant fluoracyzine.
      The normal discrimination of black and white visual stimuli in monkeys is
      restored with the systemic administration of oxymethacil in a dose of 3 mg/kg
      following disruption brought about by the effect of fluoracyzine. The
      discrimination of colored visual stimuli, as in the norm, is restored following
      the systemic administration of oxymethacil in a dose of 4 mg/kg. The results
      obtained attest to the corrective properties of oxymethacil.

PMID- 8290037
TI  - The influence of activation of the superior colliculi on convulsive activity
      during picrotoxin kindling.
AB  - It has been demonstrated in experiments in rats in which kindling was induced by
      repeated subconvulsive doses of picrotoxin (1.0 mg/kg) that the bilateral
      microinjection of picrotoxin, bicuculline, and penicillin into the deep layers of
      the superior colliculi of the corpora quadrigemina leads to the appearance of a
      generator of pathologically intensified excitation. An increase in the latent
      period of the initial convulsive manifestations, the suppression of clonic-tonic
      convulsive attacks, as well as the prevention of generalized epileptic activity
      induced by the systemic utilization of picrotoxin were observed under the
      conditions of the appearance of a generator of pathologically intensified
      excitation. An inference was drawn regarding the role of the superior colliculi
      in the mechanisms of the suppression of convulsive activity and regarding their
      inclusion in the antiepileptic system.

PMID- 8290038
TI  - Comparative characterization of the background activity of neurons of the central
      cerebellar neurons of the awake cat.
AB  - The baseline impulse activity of neurons of the central nuclei of the cerebellum
      was investigated in awake cats under chronic experimental conditions through the
      use of various methods of statistical analysis. Differences were identified,
      along with the predominance of irregular impulse streams in the neurons of all
      the nuclei, in the relationship of individual varieties of the baseline activity
      of the neurons, both with respect to the pattern of the activity and with respect
      to the dynamics of the repetition of the interimpulse intervals, as well as with
      respect to other statistical characteristics of the distribution of the
      interimpulse intervals in each nucleus. It is hypothesized that the variations in
      the baseline impulse activity of neurons of individual nuclei are determined by
      their cytoarchitectonic features and by the varied distinctness of the
      correlating tonic afferent and cerebellar cortical influences.

PMID- 8290039
TI  - A possible function of Schwann cells in neuromuscular transmission in the frog.
AB  - The total treatment of the cutaneous pectoris muscle of the frog with rabbit
      antiserum to galactocerebrosides leads to the slowing of the development of the
      depression of end-plate currents when the transected preparations are stimulated
      in normal Ringer's solution at a frequency of 100 imp/sec. Changes are not
      observed in the quantal composition and the binomial characteristics of
      neuromuscular transmission when nontransected preparations are stimulated at 1
      imp/sec in solutions containing magnesium. The action of the antiserum to
      galactocerebrosides elicits an increase in the relative number of typical
      miniature end-plate potentials that are characterized by a prolonged time course.
      The electron microscopic investigation of the preparations demonstrates the
      absence of lysis of the schwann cells in the preparations subjected to treatment
      with antiserum. It is possible that the effects obtained reflect changes in the
      functional state of the Schwann cells of the synaptic region that arise as the
      result of the fixation on their membrane of antibodies to galactocerebrosides.

PMID- 8290040
TI  - The role of permeability to calcium in the formation of the level of local blood
      supply of the cerebral cortex.
AB  - The features of the effect of some calcium antagonists on local brain blood flow
      in the sensorimotor, auditory, and visual regions of the cerebral cortex of
      rabbits have been investigated in chronic experiments on rabbits using the
      hydrogen clearance technique, and the hydrational state of the tissue was
      investigated by means of impedometry. It was established that during the
      intravenous administration of various calcium antagonists there are individual
      features in the effects on particular functional zones of the cerebral cortex of
      rabbits. The data obtained permitted the identification of regions of mainly
      increased local brain blood flow during the use of the calcium antagonists we
      were investigating. The results of three-frequency impedometry permit a judgment
      regarding the changes in the degree of hydration of brain tissue during the use
      of calcium antagonists.

PMID- 8290041
TI  - Megadose corticosteroids in multiple sclerosis.

PMID- 8290042
TI  - Clinical characteristics in a kindred with early-onset Alzheimer's disease and
      their linkage to a G-->T change at position 2149 of the amyloid precursor protein
      gene.
AB  - Patients from five generations of a family developed presenile Alzheimer's
      disease (AD) early in the fifth decade. Recent memory, information-processing
      speed, sequential tracking, and conceptual reasoning were the earliest cognitive
      functions affected. Language and visuoperceptual skills were largely spared early
      in the course of the disease. Later, there were progressive cognitive deficits
      and inability to perform the activities of daily living. Death occurred, on
      average, 6 years after onset. Three autopsies in affected members revealed
      cerebral amyloid deposits and neurofibrillary tangles. Clinical and pathologic
      features were typical for familial AD. Direct DNA sequencing revealed a G-->T
      change at position 2149 of the amyloid precursor protein (APP) gene that resulted
      in the substitution of phenylalanine for valine in the transmembrane domain of
      the mature protein. This mutation was present in DNA from all four examined
      affected individuals and linked to the disease with a lod score of 3.25, and was
      the most probable cause of AD in this family.

PMID- 8290043
TI  - The British Isles survey of multiple sclerosis in twins.
AB  - During a 27-month recruitment period, we identified 146 individuals with multiple
      sclerosis (MS) who have a twin. A single clinician interviewed and examined 105
      pairs of twins, and we confirmed zygosity using minisatellite probes. Including
      two suspected cases, 11 of 44 (25%) monozygotic twin pairs were concordant
      compared with two of 61 (3%) dizygotic twin pairs--two of 33 (6%) like-sexed and
      zero of 28 (0%) opposite-sexed. MRI was performed in 64 of 105 co-twins, and
      showed abnormalities consistent with demyelination in 13% of monozygotic and 9%
      of dizygotic co-twins who were clinically unaffected. These findings are similar
      to the results of most previous studies of MS in twins in which zygosity was not
      unequivocally established and where the majority of clinically unaffected co
      twins were not studied by MRI; the difference in concordance rates in monozygotic
      and dizygotic twins indicates a significant genetic component in the etiology of
      MS.

PMID- 8290044
TI  - Two-dimensional tracing and tracking in patients with Parkinson's disease.
AB  - We investigated the execution of two-dimensional, visually guided hand movements
      in patients with Parkinson's disease (PD) and in control subjects. Testing
      involved moving an unseen handle along a straight line or a sinusoidal path over
      a horizontally placed digitizing tablet. The path was displayed on a computer
      screen together with a pointer that represented the handle's location. The size
      of all video displays corresponded, with a 1:1 ratio, to the actual movements. We
      used the following tests. (1) Tracing, in which each subject was asked to move
      the pointer over the entire path, from left to right, with no speed requirements.
      (2) Tracking along a displayed path: a small circle moved along the path at a
      speed of 4, 7, or 10 mm/sec. The subject was asked to maintain the pointer inside
      the circle throughout its movement. When missed, the circle stopped moving until
      the pointer was again brought inside it. (3) Tracking along an unseen path: same
      as (2), except that the path was not displayed. Analysis of movement accuracy and
      of movement kinematics revealed that the patient's ability to control the
      direction of hand movement was impaired and that this impairment was evident in
      tracing as well as in tracking, was greater for sinusoidal than for straight
      movement paths, and was independent of movement speed.

PMID- 8290046
TI  - Effects of the sex of myotonic dystrophy patients on the unstable triplet repeat
      in their affected offspring.
AB  - The mutation responsible for myotonic dystrophy (DM) is an unstable expansion of
      the CTG repeat within the myotonin protein kinase gene. To examine whether the
      parental origin of the expanded repeat influences the repeat size in offspring,
      we studied 51 father-child and 59 mother-child pairs with DM. Small expansions in
      fathers resulted in larger size expansions in their offspring, while large
      paternal expansions resulted in less size change in their offspring. However,
      there was no correlation between maternal size expansion and size increase in
      offspring for either congenital or noncongenital DM. These data suggest that the
      sex of the affected parent influences the unstable expansion of the repeat in DM
      offspring. While some evidence suggests that DNA methylation status cannot
      explain this observation, the mechanism for differential maternal/paternal
      transmission expansion is currently unknown.

PMID- 8290045
TI  - Cerebral involvement in McLeod syndrome.
AB  - McLeod syndrome is an Xp21-linked Kell blood group variant due to lack of
      erythrocyte protein Kx with associated RBC membrane dysfunction such as
      acanthocytosis. A man with this syndrome developed chorea and slight
      neuropsychological impairment. He had caudate atrophy on cerebral imaging and
      reduced striatal dopamine D2-receptor binding on single-photon emission computed
      tomography. Since Xp21 was partly deleted in the patient, the missing gene
      product (possibly Kx) may be essential for the integrity of the striatum.

PMID- 8290047
TI  - Polymorphonuclear leukocyte functions and multiple sclerosis.
AB  - We tested peripheral blood from 60 patients with definite multiple sclerosis (MS)
      and 60 healthy controls for polymorphonuclear leukocyte (PMNL) functions and
      found significant disorders in adherence (9.07% +/- 8.18% for patients versus
      28.97% +/- 5.76% for controls), chemotaxis (18.32 +/- 3.1 for patients versus
      30.49 +/- 4.52 for controls), phagocytosis (73.6 +/- 25.25 for patients versus
      111.2 +/- 25.7 for controls), and bactericidal action (10.35% +/- 5% for patients
      versus 25.09% +/- 4.82% for controls). All differences were significant (p <
      0.001). We confirmed the results by retesting 3 to 8 months later. The depressed
      PMNL functions in MS patients may explain their increased susceptibility to
      infections of the respiratory, digestive, and urinary tracts.

PMID- 8290048
TI  - Early presentation of hemispheric intracerebral hemorrhage: prediction of outcome
      and guidelines for treatment allocation.
AB  - Criteria for selecting patients for possible surgery in the management of
      intracerebral hemorrhage (ICH) are needed to plan a prospective therapeutic
      evaluation of surgical intervention. This study specifically addressed patients
      seen in the emergency room within a few hours of the ictus, many of whom were
      still awake, to identify and subsequently exclude from surgical procedure those
      expected to recover completely and those expected to die regardless of treatment.
      We retrospectively studied 75 patients evaluated at a mean time of 3 hours and 37
      minutes after hemispheric ICH to determine factors that would predict both good
      and poor outcomes at the time of discharge. Eighty percent of our patients
      presented within 6 hours of symptom onset. These patients were younger and had
      more severe lesions than did those presenting later, yet most were still awake
      (mean admission Glasgow Coma Scale [GCS] score = 11.0). Using multivariate
      regression, we created two models. The first model predicts independent outcome,
      ie, Rankin 0 to 2, of all patients with a GCS score greater than 9 on admission
      who do not undergo surgery. The significant factors in this model were hemorrhage
      diameter, intraventricular extension, and age. The second model predicts poor
      outcome, ie, Rankin 5 and death, of all patients. GCS score, hemorrhage volume,
      age, and gender were the important factors in this model. We conclude that ICH
      patients presenting early to the emergency room have more severe lesions
      radiologically, although their initial clinical status may not be different from
      those seen late. Our models should identify and thus exclude those with very good
      and very poor prognoses from future randomized surgical trials.

PMID- 8290049
TI  - Analysis of the IgG subclass distribution and inflammatory infiltrates in
      patients with anti-Hu-associated paraneoplastic encephalomyelitis.
AB  - Using immunohistochemistry, we studied the IgG subclass distribution of the anti
      Hu antibody in serum, nervous system, and tumor of patients with anti-Hu
      associated paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN). The
      nervous system was also examined for deposits of complement and the distribution
      and type of inflammatory cells. IgG1 and IgG3 were the predominant isotypes of
      the anti-Hu IgG in serum, nervous system, and tumor. A few patients also had anti
      Hu IgG2, but this isotype was not consistently present in all the regions of the
      nervous system studied. There was no correlation between neurologic symptoms and
      specific anti-Hu isotype, nor was there evidence that different anti-Hu isotypes
      recognized specific brain regions. Although IgG1 and IgG3 can activate
      complement, only weak complement reactivity was found, and that only in a few
      areas of the nervous system. This finding, in addition to the absence of natural
      killer (NK) cells, suggested that complement-mediated toxicity and antibody
      dependent cell cytotoxicity mediated by NK cells are not pathogenic in PEM/PSN.
      Inflammatory infiltrates included CD19+ (B cells) and CD4+ (helper/inducer) cells
      in the perivascular spaces, and lymphocytes bearing CD8+CD11b- markers (cytotoxic
      T cells) in the interstitial spaces. Infiltrates of EBM11+ (monocyte/macrophage)
      cells were identified in the perivascular spaces (macrophage phenotype) and in
      those interstitial regions (microglial phenotype) with severe pathologic changes.
      The ability of the IgG1 and IgG3 isotypes to bind Fc receptors may have played a
      role in the recruitment of these monocyte/macrophage cells.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8290050
TI  - Oculomotor palsy from minor head trauma: initial sign of intracranial aneurysm.
AB  - Minor head trauma precipitated oculomotor nerve palsies in two patients who
      subsequently were discovered to have ipsilateral posterior communicating artery
      aneurysms. A history of minor trauma should not dissuade investigation for
      underlying causes of oculomotor nerve palsy, including intracranial aneurysm.

PMID- 8290051
TI  - Micrographia due to focal cerebral lesions as seen in the dysarthria-clumsy hand
      syndrome.
AB  - Five patients with dysarthria-clumsy hand syndrome developed micrographia. Four
      had lacunar infarctions involving the putamen or the genu of the internal
      capsule; the fifth patient had a small hemorrhage in the putamen. Micrographia
      may be a sign of focal cerebral disease, and basal ganglia dysfunction may be
      involved in the supratentorial dysarthria-clumsy hand syndrome.

PMID- 8290052
TI  - Myasthenia gravis: rarity of gallstone formation.
AB  - There is an increase in the production of gallbladder stones (cholelithiasis)
      following gastrectomy associated with vagotomy; we hypothesized that in the
      presence of constant stimulation of the vagal system, there should be decreased
      production of gallstones. Forty-two myasthenia gravis patients taking continuous
      anticholinesterase medications underwent ultrasound study of the gallbladder;
      only one patient, aged 62, had gallstones. In the control group of 112
      nonmyasthenics matched for age and ethnic origin, 45 had stones. This study
      suggests that cholinergic medications protect against gallstones.

PMID- 8290053
TI  - Musical auditory hallucinations caused by a brainstem lesion.
AB  - A man with left-sided deafness developed right-sided hearing loss after
      hypertensive hemorrhage at the right pontine tegmentum and began to experience
      ipsilateral musical hallucinations. Two weeks later, the right hearing returned,
      and the hallucinations disappeared. Auditory hallucinations due to brainstem
      lesions may be musical in nature and associated with hearing loss.

PMID- 8290054
TI  - A case of Down's syndrome with diffuse Lewy body disease and Alzheimer's disease.
AB  - Almost all Down's syndrome (DS) patients over the age of 35 to 40 years have
      histologic features of Alzheimer's disease (AD). However, the presence of
      extrapyramidal features in up to 36% of these patients has no satisfactory
      pathologic explanation. We report an older patient with DS, dementia, and
      parkinsonian signs who showed pathologic changes of Parkinson's disease and
      cortical Lewy bodies in addition to AD. These parkinsonian changes may be related
      to chromosome 21 abnormalities.

PMID- 8290055
TI  - The impact of blinding on the results of a randomized, placebo-controlled
      multiple sclerosis clinical trial.
AB  - In the randomized, placebo-controlled, physician-blinded Canadian cooperative
      trial of cyclophosphamide and plasma exchange, neither active treatment regimens
      (group I: i.v. cyclophosphamide and prednisone; group II: weekly plasma exchange,
      oral cyclophosphamide, and prednisone) were superior to placebo (group III: sham
      plasma exchange and placebo medications) using the blinded, evaluating
      neurologists' assessments of disease course (primary analysis). All patients were
      examined by both a blinded and an unblinded neurologist at each assessment in
      this trial. We compared the blinded and unblinded neurologists' judgment of
      treatment response and analyzed the clinical behavior of patients who correctly
      guessed their treatment. The unblinded (but not the blinded) neurologists' scores
      demonstrated an apparent treatment benefit at 6, 12, and 24 months for the group
      II patients (not group I or placebo; p < 0.05, two-tailed). There were no
      significant differences in the time to treatment failure or in the proportions of
      patients improved, stable, or worse between the group II and group III patients
      who correctly guessed their treatment assignments and those who did not.
      Physician blinding prevented an erroneous conclusion about treatment efficacy
      (false positive, type 1 error).

PMID- 8290056
TI  - Sumatriptan blocks neurogenic inflammation in the peripheral nerve trunk.
AB  - We tested the action of intraperitoneal sumatriptan, a 5-HT1D receptor agonist
      that aborts migraine headaches, using a model of neurogenic inflammation induced
      by capsaicin applied to the rat sciatic epineurium. Sumatriptan prevented the
      development of capsaicin-induced hyperemia without inducing pretreatment
      vasoconstriction or altering AV shunt flow. The findings indicate that
      sumatriptan prevents "neurogenic" vasodilation by a mechanism other than
      vasoconstriction or changes in AV shunt flow.

PMID- 8290057
TI  - Failure to transfer multiple sclerosis into severe combined immunodeficiency mice
      by mononuclear cells from CSF of patients.
AB  - To confirm the reported transfer of multiple sclerosis (MS) by CSF cells, we
      injected CSF cells from six MS patients in the exacerbation stage into the
      cisterna magna of 18 severe combined immunodeficiency mice. No clinical
      neurologic abnormalities or light- or electron-microscopic pathologic changes
      were present in any transferred mice, and the reported results could not be
      reproduced.

PMID- 8290058
TI  - Ethical considerations raised by the approval of interferon beta-1b for the
      treatment of multiple sclerosis.

PMID- 8290059
TI  - The first American epileptologists: William P. Spratling, MD, and Rosewell Park,
      MD.

PMID- 8290060
TI  - Measurement and cytologic demonstration of 5-S-cysteinyldopa for the clinical
      diagnosis of primary leptomeningeal melanoma.

PMID- 8290061
TI  - Acute pseudobulbar mutism with good functional recovery.

PMID- 8290062
TI  - Recurrent attacks with skew deviation, torsional nystagmus, and contraction of
      the left frontalis muscle.

PMID- 8290063
TI  - Progressive spastic paraparesis revealing primary hyperparathyroidism.

PMID- 8290064
TI  - Epileptic seizure induced by a product marketed as a "brainwave synchronizer".

PMID- 8290065
TI  - Genetic expression of a transthyretin mutation in a case of amyloidotic
      polyneuropathy occurring in an African.

PMID- 8290066
TI  - Anti-Hu-associated peripheral nerve and muscle microvasculitis.

PMID- 8290067
TI  - Interferon beta treatment of multiple sclerosis.

PMID- 8290068
TI  - Interferon beta treatment of multiple sclerosis.

PMID- 8290069
TI  - Interferon beta treatment of multiple sclerosis.

PMID- 8290070
TI  - Interferon beta treatment of multiple sclerosis.

PMID- 8290071
TI  - Interferon beta treatment of multiple sclerosis.

PMID- 8290072
TI  - Interferon beta treatment of multiple sclerosis.

PMID- 8290073
TI  - Interferon beta treatment of multiple sclerosis.

PMID- 8290074
TI  - Interferon beta treatment of multiple sclerosis.

PMID- 8290075
TI  - Interferon beta treatment of multiple sclerosis.

PMID- 8290076
TI  - Myopathy in congenital amaurosis.

PMID- 8290077
TI  - Subarachnoid hemorrhage.

PMID- 8290078
TI  - Intracranial hypotension.

PMID- 8290079
TI  - Nonvasculitic neuritis.

PMID- 8290080
TI  - Nonvasculitic neuritis.

PMID- 8290081
TI  - Seizures in the elderly.

PMID- 8290082
TI  - Capsular warning syndrome.

PMID- 8290083
TI  - Reaction times and L-dopa.

PMID- 8290084
TI  - Familial vestibulopathy: a new dominantly inherited syndrome.
AB  - Three patients who presented with episodic vertigo followed by gait imbalance and
      oscillopsia had profound bilateral vestibular loss despite normal hearing. All
      had a parent with similar findings. The patients, their affected parent, and
      multiple other family members had a history of migraine headaches, although
      several of the latter had normal vestibular function. Acetazolamide stopped or
      markedly decreased the frequency of vertigo attacks in the three patients treated
      but had little effect on the chronic vestibular loss. This is the first report of
      a dominantly inherited bilateral vestibulopathy associated with normal hearing.

PMID- 8290085
TI  - Epileptic seizures associated with intrathecal baclofen application.
AB  - We report the clinical and EEG findings in three patients presenting with
      seizures associated with intrathecal baclofen application for treatment of
      spasticity. All patients had a history of traumatic brain injury, while one
      patient also suffered a spinal cord injury. Two patients experienced their first
      seizure following intrathecal baclofen test bolus injection. Another patient had
      convulsions on two occasions: following postoperative baclofen dose adjustment,
      and after sleep deprivation. Structural brain disease seems prerequisite for
      baclofen to exert epileptogenic activity, since seizures have not occurred in
      patients receiving intrathecal baclofen for spasticity of solely spinal origin.
      Antiepileptic medication permitted the continuation of intrathecal baclofen
      treatment in the three patients.

PMID- 8290086
TI  - Impairment, disability, and handicap in multiple sclerosis: a population-based
      study in Olmsted County, Minnesota.
AB  - We studied functional status of MS patients in a geographically based cohort in
      Olmsted County, Minnesota. The 162 definite MS patients who were alive and
      residing in the study area on December 1, 1991, constituted the MS prevalence
      disability cohort. We identified 179 cases of definite or probable MS, providing
      an overall sex- and age-adjusted prevalence rate of 167.5 per 100,000. Median
      duration of MS from onset was 15.4 years, and median age on prevalence date was
      47.5 years. The Minimal Record of Disability for MS determined the degree of
      impairment, disability, and handicap of the entire cohort within 4 months of the
      prevalence date. The frequency of Expanded Disability Status Scale scores of the
      MS prevalence cohort showed a bimodal distribution with peaks at 1 and 6.5 (3.5
      [1 to 9.5], median [range]). Approximately one-third of the cohort had marked
      paraparesis, paraplegia, or quadriplegia. One-fourth of all patients needed
      intermittent or almost constant catheterization for bladder dysfunction. Few
      patients (3.7%) reported severe decrease in mentation or dementia requiring
      supervision. Many patients (53.1%) were working full-time. Most patients (72.2%)
      maintained their usual financial standard without external support. There were no
      differences in level of impairment, disability, or handicap observed between the
      subgroup of 122 patients (75.3%) who are incident cases (onset of disease as
      residents of Olmsted County) compared with the entire prevalence cohort. This
      geographically based study of MS demonstrates that the functional status is more
      favorable than previously recognized.

PMID- 8290087
TI  - Epilepsy, psychosis, and schizophrenia: clinical and neuropathologic
      correlations.
AB  - This study examines the relationship between epilepsy and psychosis. It compares
      clinical, EEG, and neuropathologic data from a group of subjects who had both
      epilepsy and psychosis with similar information from another group of patients
      who had epilepsy but no evidence of psychotic illness. We examined, blind to
      clinical diagnosis, gross and microscopic material from whole-brain specimens
      from 10 patients diagnosed with epilepsy plus schizophrenia-like psychosis, nine
      subjects diagnosed with epilepsy plus "epileptic psychosis," and 36 individuals
      with epilepsy (21 from an epileptic colony and 15 from the community at large)
      who had no history of psychosis (n = 10 + 9 + 21 + 15 = 55). We abstracted case
      histories without knowledge of pathologic findings. Epileptic colony patients had
      an earlier age at onset of seizures, while epileptic colony and epileptic
      psychosis patients had more frequent seizures. Epileptic individuals in the
      community died at a younger age than did epileptic patients in long-stay hospital
      care. Psychotic epileptic patients had larger cerebral ventricles, excess
      periventricular gliosis, and more focal cerebral damage compared with epileptic
      patients who had no psychotic illness. Epileptic patients with schizophrenia-like
      psychosis were distinguished from all other groups by a significant excess of
      pinpoint perivascular white-matter softenings. We found that mesial temporal
      sclerosis and temporal lobe epilepsy occurred with equal frequency in the
      psychotic and nonpsychotic groups; generalized seizures occurred more frequently
      in the psychotic epileptics and the epileptic colony epileptics than in the
      community epileptic controls.

PMID- 8290088
TI  - Hippocampal sclerosis without detectable hippocampal atrophy.
AB  - Six patients from three centers had MRI and pathologic evidence of hippocampal
      sclerosis but no detectable hippocampal atrophy. Loss of normal internal
      structure and T1- and T2-weighted signal abnormalities allowed the MRI diagnosis
      of unilateral hippocampal sclerosis when hippocampal volume measurements were
      normal and symmetric. Although accurate hippocampal volume measurements will
      determine the most severely affected side in most cases, volume measurements or
      atrophy alone will not always detect all MRI-visible pathology. Additional
      detailed MRI assessment is required before structural abnormality of the
      hippocampus is excluded on the basis of volume measurements.

PMID- 8290089
TI  - Status epilepticus and antiepileptic medication levels.
AB  - To investigate the association between withdrawal from antiepileptic drugs (AEDs)
      and status epilepticus (SE), we evaluated AED levels at the time of, and prior
      to, an episode of SE in 65 patients with epilepsy. At least one AED was
      therapeutic in 65% of patients at the time of SE, and all prescribed AEDs were
      therapeutic in 48%. Ten patients had subtherapeutic AED levels before, and at the
      time of, SE. Sixteen patients with previously therapeutic levels (25%) had one or
      more subtherapeutic AED level at the time of SE. Many of the patients had other
      acute or remote factors that could be associated with SE, and 46 had had previous
      episodes of SE. Low AED levels or withdrawal can explain only some cases of SE.
      Citing AED irregularity as the major cause of SE in patients with epilepsy
      oversimplifies a complex, poorly understood situation.

PMID- 8290090
TI  - Is idiopathic parkinsonism the consequence of an event or a process?

PMID- 8290091
TI  - Periventricular heterotopia and epilepsy.
AB  - We report a family with nodular subependymal masses of heterotopic gray matter
      occurring in six members in four generations. Only female members of the family
      are affected, and there is a high rate of spontaneous abortion, consistent with X
      linked dominant inheritance, and lack of viability in affected males. Both in
      this family and in sporadic cases of subependymal heterotopias there is a high
      frequency of convulsive disorders, suggesting that epilepsy may be the major
      clinical manifestation of this developmental defect.

PMID- 8290092
TI  - Anticonvulsant withdrawal-emergent psychopathology.
AB  - We prospectively investigated psychopathology in 32 epilepsy inpatients openly
      withdrawn from all antiepileptic drugs (AEDs) prior to entering a controlled
      trial of an investigational AED. Psychiatric ratings and seizures increased
      significantly with AED discontinuation. Anxiety and depression were the most
      prominent symptoms. Thirty-eight percent of patients developed moderate-to-severe
      psychopathology, and 28% dropped out of the study at various stages due to
      psychiatric symptoms. In 22 patients openly restarted on AEDs, psychiatric
      ratings returned to baseline within 2 weeks. Increases in partial seizures were
      weakly related to emergent anxiety and depression. Increases in generalized
      seizures were related to increases in global impairment but not to increases in
      specific psychopathology. AED withdrawal-emergent psychopathology was not fully
      explained by increases in seizures, demographic factors, or psychiatric history
      and may be partially due to pharmacodynamic effects following drug
      discontinuation.

PMID- 8290093
TI  - Prevalence of essential tremor: a door-to-door survey in Terrasini, Sicily.
      Sicilian Neuro-Epidemiologic Study Group.
AB  - As part of a door-to-door neuroepidemiologic survey, we investigated the
      frequency and distribution of essential tremor (ET) in a Sicilian municipality.
      During phase 1, we administered a screening instrument for tremor to 7,653
      persons residing in Terrasini (Palermo province). During phase 2, neurologists
      evaluated those subjects who had screened positive. The diagnoses, based on
      specified clinical criteria, were reviewed to increase reliability across
      neurologists. We found 31 subjects affected by ET (17 men, 14 women); 11 patients
      (35.5%) reported a familial aggregation. The prevalence of ET as of November 1,
      1987, was 405.1 per 100,000 for the total population, and 1,074.9 per 100,000 for
      those 40 years old or older. The prevalence increased with advancing age for both
      sexes and was slightly but consistently higher in men. Comparison with other
      studies suggests striking geographic variation, which may reflect genetic
      differences.

PMID- 8290094
TI  - Study of genetics, epidemiology, and vitamin usage in familial spina bifida in
      the United States in the 1990s.
AB  - We analyzed family structure, genetic patterns, epidemiology, and vitamin usage
      in a series of families with multiple cases of spina bifida (familial SB). Among
      6,491 individuals ascertained in 72 families with familial SB, we identified 180
      patients--85 males and 95 females. The number of collateral cases on the maternal
      side (49 of 3,588), analyzed by category of kinship, were significantly higher
      than those on the paternal side (16 of 2,903) (p = 0.0002). Genomic imprinting or
      a partial mitochondrial contribution are possible mechanisms for this maternal
      effect. The proportion of US-born SB families reporting some Irish ancestry (49%,
      34 of 70) or some German ancestry (50%, 35 of 70) were significantly higher than
      those for the US population at large. In contrast, the proportion of families
      reporting some African-American ancestry (1%, 1 of 70) was significantly lower.
      The elevated proportions of families with Irish and German ancestry, the high
      frequency of SB in Northern Ireland and in certain regions of Germany, the
      reduced proportion of families with African-American ancestry, and the lower
      prevalence of SB in African-Americans all suggest a genetic contribution to the
      etiology of the disorder. In our study, the proportion of mothers who used
      supplemental vitamins during the periconceptional period (29%, 47 of 163) was not
      significantly different from that in the US population at large.

PMID- 8290095
TI  - Long-term botulinum toxin treatment of focal hand dystonia.
AB  - We treated focal hand dystonia in 53 patients with botulinum toxin injections for
      up to 6 years. Eighty-one percent of the patients improved with at least one
      injection session. Sixty-five percent of the injections produced transient
      weakness. We followed 37 of the patients for at least 2 years from the start of
      treatment, 24 of whom discontinued treatment because of inadequate response, loss
      of response, inaccessibility of a treatment provider, or the expense of the
      toxin. Women, who had a greater extent and longer duration of benefit than men,
      were more likely to continue treatment. The mean interval between injection
      sessions was 6 months. In most patients, we injected the toxin into the same
      combination of muscles at each session. The dose of toxin generally fluctuated
      within a range of 20 units. Side effects were mild and transient and unrelated to
      the long-term use of botulinum toxin. Botulinum toxin injection is safe and
      effective for the long-term management of focal hand dystonia.

PMID- 8290096
TI  - Effect of entacapone, a COMT inhibitor, on clinical disability and levodopa
      metabolism in parkinsonian patients.
AB  - We studied the effect of entacapone, a selective catechol-O-methyltransferase
      inhibitor, on the bioavailability and clinical effect of levodopa in Parkinson's
      disease (PD). On day 1 (control day), nine patients received their own levodopa
      (plus benserazide) medication only; for the next 7 days they received 200 mg of
      entacapone with each dose of levodopa (tid or qid). We evaluated disability in
      the morning (8 AM) before drug administration and then at 1-hour intervals until
      6 PM on days 1, 2, and 8, using a modified motor part of the Unified Parkinson's
      Disease Rating Scale. Repeated blood samples were taken before and during the 4
      hours after the morning drugs for pharmacokinetic evaluation of entacapone and of
      levodopa and its metabolites. Added to the levodopa treatment, entacapone
      decreased clinical disability by about 16% (p < 0.05) from day 1 to day 8. The
      area under the curve (AUC) of levodopa increased by 38% (p < 0.01) after
      administration of a single dose of entacapone and by 40% (p < 0.05) after 7 days
      of multiple dosing with entacapone. Entacapone did not change the Tmax and Cmax
      values of levodopa. After 7 days of treatment with entacapone, the AUC of 3-O
      methyldopa had decreased by 44% (p < 0.01) and of homovanillic acid by 26% (p <
      0.05) as compared with treatment with levodopa alone. Four patients became
      slightly more dyskinetic during entacapone treatment than before it. The
      combination of entacapone and levodopa was well tolerated, judged by the lack of
      significant changes in hemodynamic and safety variables.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8290097
TI  - Optic tract atrophy with cerebral arteriovenous malformations: direct and
      transsynaptic degeneration.
AB  - Three patients with postgeniculate cerebral arteriovenous malformations (AVM) had
      band atrophy of the contralateral optic nerve. One patient had homonymous
      hemioptic hypoplasia. These cases might have been construed as demonstrating
      transsynaptic degeneration across the lateral geniculate nucleus to the anterior
      visual pathway. However, neuroimaging studies revealed abnormal deep venous
      drainage remote from the AVM nidus that directly involved the lateral geniculate
      nucleus and posterior optic tract.

PMID- 8290098
TI  - Cognitive deficits of men and women with Alzheimer's disease.
AB  - We performed two studies of cognitive abilities among men and women who met
      clinical criteria for Alzheimer's disease (AD). Among 46 AD patients, performance
      of women on a composite neuropsychological battery was more impaired than that of
      men when the potentially confounding effects of demographic variables were
      controlled; the largest group differences were due to significantly worse
      performance by women with AD on a naming task. Based on these initial findings,
      we next analyzed an independent data set of 647 demented subjects enrolled in the
      multicenter Consortium to Establish a Registry for Alzheimer's Disease,
      hypothesizing that the naming performance of women with AD would be significantly
      worse than that of men with this illness. Analyses controlling for demographic
      variables, or separately controlling for dementia severity, confirmed that women
      with AD performed significantly less well on the naming task and on verbal
      fluency. Women also performed less well on delayed recall, but there were no
      significant differences on other tasks. Factor analysis confirmed significant
      differences on a language factor, implying that men retain verbal skills better
      than women do during the initial stages of AD. Elderly nondemented women
      performed as well as or better than nondemented men on all comparisons. We
      conclude that there are modest differences in how men and women with AD perform
      on cognitive tasks and that differences may be discrete rather than global in
      nature.

PMID- 8290099
TI  - Risk factors for Alzheimer's disease and dementia: a case-control study based on
      the MRC elderly hypertension trial.
AB  - We surveyed 1,545 subjects--recruited into the UK Medical Research Council
      elderly hypertension treatment trial between 1982 and 1987--to detect incident
      cases of dementia, identifying 50 cases of dementia, including 31 cases of
      probable or possible Alzheimer's disease (AD). These we compared with 223
      unimpaired, unmatched controls from the same population for exposure to familial,
      cardiovascular, educational, and geographic risk factors for dementia. Our study
      confirms the association of family history of dementia with dementia (odds ratio
      [OR] = 4.36) and AD (OR = 4.69), and of advanced age with dementia (OR = 2.81).
      Rural residence exerted a protective effect for dementia (OR = 0.21) and AD (OR =
      0.28). We report near-significant associations between AD and dementia and
      several cardiovascular risk factors (ECG ischemia, systolic hypertension, and
      smoking) among subjects lacking a family history of dementia. We postulate the
      existence of a nonfamilial form of dementia transcending traditional categories
      of multi-infarct dementia and AD, more common among urban residents, and mediated
      through vascular pathology. Risk factors reported elsewhere but not confirmed in
      this study were advanced maternal age and winter season of birth.

PMID- 8290100
TI  - [Hemodynamics in the organ donor: physiopathologic and therapeutic problems].

PMID- 8290101
TI  - [The electroencephalogram for real-time neurophysiologic monitoring in anesthesia
      and intensive care].

PMID- 8290102
TI  - [Monitoring and analysis of intracranial pressure: intracranial dynamics and
      signal processing].

PMID- 8290103
TI  - [SPECT of cerebral perfusion in neuroresuscitation. First experience].

PMID- 8290104
TI  - [Real-time cardiocirculatory monitoring in cardiopulmonary-cerebral
      resuscitation].

PMID- 8290105
TI  - [Current role of the new techniques of cardiopulmonary resuscitation (CPR)].

PMID- 8290106
TI  - [Sodium bicarbonate and alkalinizing agents in the treatment of cardiac arrest].

PMID- 8290107
TI  - [Adrenaline: drug of choice in cardiovascular arrest].

PMID- 8290108
TI  - [Effect of some calcium antagonists in an experimental model of cardio-cerebral
      relationships].

PMID- 8290109
TI  - [Current role of barbiturates in cerebral protection].

PMID- 8290110
TI  - [Mechanical circulatory assistance in cardiopulmonary-cerebral resuscitation:
      reality or utopia?].

PMID- 8290111
TI  - [The organ donor: clinical aspects. An unresolved problem].

PMID- 8290112
TI  - [Cerebral blood flow: is an evaluation possible during CPR?].

PMID- 8290113
TI  - [Evoked potentials in the diagnosis of brain death].

PMID- 8290114
TI  - [Organ donation: bioethical considerations].

PMID- 8290115
TI  - [Organ donation: organizational aspects].

PMID- 8290116
TI  - [Organizational problems of organ transplantation].

PMID- 8290117
TI  - [Treatment of the brain-dead patient/organ donor].

PMID- 8290118
TI  - [Care of the organ donor: respiration and metabolism].

PMID- 8290119
TI  - [In the field of water-repellent protection ASEP A/S Conductive].

PMID- 8290120
TI  - [From Milan the road to new EEC standards for specialization schools. The
      programs of a school of general surgery].

PMID- 8290121
TI  - [The role of whortleberry anthocyanosides in the microcirculation].

PMID- 8290122
TI  - [Biliary complications after a liver transplant].
AB  - Biliary tract complications are still an important source of morbidity and
      mortality after liver transplantation. Between March 1988 and September 1991 we
      performed 111 liver transplants in 109 patients (84 men and 25 women, mean age
      44.5 +/- 1.1 year). Biliary tract reconstruction was via a choledocho
      choledochostomy (n = 107) or via a Roux limb choledochojejunostomy (n = 4). Ten
      biliary complications (11.9%) occurred (6 biliary leakage, 3 biliary strictures,
      1 biliary cast syndrome). Five patients (5.9%) necessitated operative repair
      (Roux limb choledochojejunostomy). No death was related to biliary tract
      complication.

PMID- 8290123
TI  - [Lipiodol chemoembolization in the treatment of hepatic carcinoma. Our
      experience].
AB  - Of the alternative methods of treatment to surgery in the treatment of liver
      cancer, chemoembolization with Lipiodol appears to have obtained encouraging
      results. After a preoperative study to confirm the diagnosis and staging of the
      tumour, lipiodolisation is performed: a mix of Adriamycin, Iopamidol and Lipiodol
      is injected using selective catheterism of the hepatic artery; gelfoam is then
      added. Lipiodol selectively localises in the hepatocarcinoma and has a distal
      embolising effect on the vessels of the tumour, thus necrotising it, acting as a
      carrier for chemotherapy. Since july 1990 a total of 15 hepatocarcinoma have been
      observed: 6 in healthy livers and 9 in cirrhotic livers; 3 patients recovered
      after radical surgery, 1 patient underwent associated surgery and
      chemoembolization, whereas in 11 the only therapy was chemoembolization, at six
      monthly intervals. Lipiodolisation enabled a better diagnosis to be made and was
      found to be a valuable therapeutic aid both when used alone in Inoperable
      patients and in association with non-radical surgery.

PMID- 8290124
TI  - [The surgical treatment of inflammatory aneurysms of the abdominal aorta. The
      usefulness of nuclear magnetic resonance (MR) in the preoperative diagnosis].
AB  - Inflammatory abdominal aortic aneurysms (IAAA) represent a peculiar variant
      compared with the common atherosclerotic origin of aortic aneurysms. Between
      January 1988 and March 1992, 111 aneurysmectomies were performed at our
      institution: 98 elective and 13 emergency procedures. In 10 cases (all males,
      mean age 68.5) an IAAA was found. 8/10 of those patients operated upon electively
      were studied preoperatively with MRI. All the IAAA but one were correctly
      identified preoperatively. Identification of IAAA with MRI in these cases
      improved the surgical approach. In conclusion, patients with IAAA can be operated
      upon safely especially if a preoperative diagnosis is present. MRI greatly
      improves our ability to characterize non invasively IAAA.

PMID- 8290125
TI  - [New diagnostic and therapeutic prospects in peripheral nodules of the lung:
      surgical video thoracoscopy].
AB  - The new findings and results of laparoscopic surgery lead us to apply this
      technique in thoracic surgery. Thoracoscopy is an old diagnostic procedure, but
      advanced imaging techniques, improved optics and new classes of instrument have
      paved the way for many diagnostic and therapeutic approaches, before not
      feasible. Now it is possible to treat spontaneous pneumothorax, removal of
      mediastinal and peripheral tumors, with minimally invasive surgery. It is our
      belief that thoracoscopic surgery will be a valuable tool in the near future for
      a variety of chest disorders.

PMID- 8290126
TI  - [Video laparoscopic cholecystectomy. An analysis of our initial experience].
AB  - The paper analyses the authors' initial experience of video laparoscopic
      cholecystectomy, outing the difficulties and incidence of morbidity in the
      preliminary group of 38 patients. The details of complications and their
      pathogenesis are also reported.

PMID- 8290127
TI  - [The impact of conventional proctocolectomy on sexual function].
AB  - Seventy-one women who had a proctocolectomy for ulcerative colitis (n. 41) or
      Crohn's disease (n. 30) were interviewed in the follow-up clinic for
      gynaecological problems and fertility. Forty-nine per cent (35/71) of the women
      had a distressing vaginal discharge after proctocolectomy, compared with 9%
      before surgery. At the gynaecological examination 45% (32/71) had a heavy vaginal
      secretion without any signs of an acute vaginal infection. In 68% (30/44) fluid
      retention in the vagina was associated with a caudally firmly-fixed and dilated
      posterior vaginal fornix. Twelve per cent (8/66) of the women reported
      dyspareunia before surgery. After surgery, 27% (18/66) complained of this
      symptom. Fertility was significantly reduced after surgery since only 37% (10/27)
      of the women who attempted to become pregnant succeeded within five years follow
      up. The corresponding figure before surgery was 72% (39/54). Those who conceived
      went through pregnancy and parturition without any incident, 6 of 24 delivered by
      cesarean section. Fifty-seven men who had a proctocolectomy for ulcerative
      colitis (n.41) or Crohn's disease (n. 30) were interviewed in the follow-up
      clinic for the presence of sexual disturbances and their incidence was studied.
      Fifty-seven per cent of elderly patients (above 40 years old) complained of
      reduced libido and sexual satisfaction. In younger patients (below 40 years old)
      33% complained of an impaired quality of sexual life and 22% complained of an
      impaired sexual satisfaction. However, despite some sexual dysfunction, 56%
      reported improved sexual life and 67% improved sexual satisfaction. This may be
      explained by improved general health and increased libido after removal of
      diseased bowel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290128
TI  - [Proctological surgery in the day-hospital regimen].
AB  - 567 haemorrohoidectomies 83 of which total haemorrhoidectomies for piles with
      surgical indications, were performed with recourse to day-hospital admission. The
      authors examine the results of this experience and advise this therapy and this
      type of admission for pathologies with different cost/benefit ratio.

PMID- 8290129
TI  - [Breast carcinoma in the elderly patient: which treatment?].
AB  - We here describe our experience of the treatment of "breast cancer" in the
      elderly. The results in this group of patients (37 over 75 years) are like the
      younger group if: the local control is done; hormonotherapy is prescribed;
      chemotherapy is done even in the 70-80-year-old group. If a radical mastectomy
      isn't impossible in the patients over 80, even a simple mastectomy is safe. In
      this patients a conservative local treatment of the breast is not mandatory. Our
      over-75-year-old patients have no psychological problem related to mastectomy.
      They often don't accept obligatory radiotherapy after the conservative treatment
      of breast cancer, and moreover the breast cancer in the elderly is usual smaller,
      fibrotic and bigger than 3 cm. Lymph nodal status isn't important for overall
      survival, but only for the eventual chemotherapeutic treatment, so in patients
      over 80 year-old simple mastectomy is sufficient because we don't use
      chemotherapy for the general conditions of the same. The local control of
      axillary lymph nodes is obtained with radiotherapy if necessary. Screening for
      breast cancer must also include 70-75-year-old patients. Why is the breast cancer
      in elderly like the others patients? Some authors have seen that the immuno
      reaction around the cancer in elderly is less than the same reaction observed in
      younger patients. So in the elderly there is a smaller production of "growth
      factors" important for the growth of the tumor and of "angiogenesis factor",
      fundamental for the initial growth of the cancer.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8290130
TI  - [Caustics-induced lesions of the gastrointestinal tract].
AB  - Ingestion of a corrosive agent results in a life-threatening clinical condition
      that requires emergency intensive care and often surgical intervention. Treatment
      is multifactorial and varies with the extent and depth of the injury. We report a
      case of a young 24-year-old man with accidental ingestion of sulphonic acid.
      After 1 month he developed a progressive dysphagia. Early endoscopic examination
      showed grade III injury to both the esophagus and stomach with severe and
      undilatable stricture of the antrum. Therapy included total parenteral nutrition
      and antibiotics. Repeat endoscopic examinations on days 30 and 40 showed
      progressive healing of the esophageal injuries, but confirmed a complete antral
      stenosis. After two months a large antecolic jejuno-gastroplasty was performed on
      the anterior wall of the stomach. The postoperative course was regular, and
      endoscopic examination showed complete healing of the injuries.

PMID- 8290131
TI  - [Gastric volvulus. A clinical therapeutic contribution].
AB  - Gastric volvulus is an infrequent event and few clinical cases are an important
      experience. Diagnosis, both clinical and radiological, is not difficult if you
      think of gastric volvulus; abdomen X-ray is often sufficient to clear up
      diagnostic doubts. First diagnosis can be quickly confirmed by X-ray examination
      of digestive organs that provides us with further information: contemporaneous
      ulcerative of neoplastic lesions, characteristics of bowels whirling round.
      Endoscopic and manometric evaluation must be performed only in recurrent or
      chronic cases, when there's no symptom of clinical urgency. Authors describe
      their experience of three cases observed in the last ten years and underline the
      importance of deciding and performing the surgical treatment quickly to avoid
      serious complications, in all doubtful cases. It is important to carry out an
      operation compared to the pathogenesis of volvulus: generally gastropexy is
      sufficient while radical operations are executed only in cae of gastric necrosis
      or in the presence of gastric neoplasms or ulcerative lesions.

PMID- 8290132
TI  - [Chronic anemia due to Meckel's diverticulum. The diagnostic and therapeutic
      considerations].
AB  - Meckel's diverticulum is a frequent embryologic residual organ. The importance of
      considering this diagnosis in the young adult presenting chronic hypochromic
      [correction of hyperchromic] anemia, despite the difficulties of the same, is
      emphasized. The condition to be satisfied is the complete excision of Meckel's
      diverticulum, to avoid leaving ectopic mucosa residuals, so we think it useful to
      resect an ileal sleeve.

PMID- 8290133
TI  - [The surgical treatment of perforated colonic diverticulitis].
AB  - The authors report a consecutive series of 52 patients who underwent urgent
      operation because of peritonitis by perforated diverticulitis. Urgent colonic
      resection achieves the best results.

PMID- 8290134
TI  - Our experience in pancreatic trauma.
AB  - The authors, with this works, call fellow members attention, how is complicate
      the diagnosis and the following surgical treatment of the associated lesions
      caused by pancreatic trauma. The pancreatic traumas are today object of
      discussion for the surgical treatment, and for the lesions associated. In this
      work is described the experience of some years accumulated in the Emergency
      Department of the Liguria Region.

PMID- 8290135
TI  - [Recurrent inguinal hernia. The surgical procedure and technic].
AB  - The authors describe two years and six months of personal experience in the
      treatment of recurrent inguinal hernia with polypropylene mesh. There was a
      follow-up with controls every 6 months with excellent results. From the data of
      the operation we programmed a further control 1'after 5 and 10 years. Considering
      the limited number of cases and the fact that the follow-up is not yet at
      completion, the information is provided as preliminary.

PMID- 8290136
TI  - [The use of magnetic tracers in hemodynamics. A proposed model study].
AB  - Velocity of blood flow is critical in specific clinical situations. Available non
      invasive blood velocimeters gives only qualitative informations; quantitative
      estimates can be obtained invasively. We investigated the possibility of
      estimating the velocity of fluids using magnetic tracer. A model for the laminar
      blood flow inside a vessel was developed. A biomagnetometer was used to measure
      the fluid tracer velocity. The experimental setup was designed to mimic blood
      flow. A PVC tube simulated the vessel. The tube was connected to a bottle of
      normal saline. The tracer injection took place 25 cm distal to the saline bottle.
      The system was calibrated to a constant flow velocity of about 1 cm/s. A
      paramagnetic fluid (Magnevist, Schering, Berlin) was adopted as a tracer. In each
      session an amount of 2 cm3 was injected into the tube within 5 seconds. The
      recording equipment consisted of a second order gradiometer (baseline 7 cm, pick
      up coil diameter 1.5 cm) coupled to a rfSQUID magnetometer. The recording
      bandwidth was dc-3 Hz, the sampling rate 32 Hz with 12 bit digitalization. The
      biomagnetic system was positioned immediately above the tube 55 cm away from the
      injection site. The total recording time for each session was 240 seconds. The
      injection of the tracer took place 60 seconds after the beginning of the data
      acquisition. Five measuring sessions in the earth magnetic field were performed
      at first and showed a low signal-to-noise ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290137
TI  - [An esophagoaortic fistula due to a foreign body].
AB  - Starting from a case of aortoesophageal fistula caused by a foreign body, some
      aspects of the treatment of upper gastrointestinal hemorrhage of uncertain
      etiology are discussed. The time between bleeding and perforation often notes it
      possible to perform resolutive diagnostic tests (aortography, esophagoscopy, CT).

PMID- 8290138
TI  - [Caroli's disease associated with cholangiocarcinoma. A case of our own
      observation].
AB  - The authors report a case of Caroli's disease associated with cholangiocarcinoma.
      The patient presented with pain and jaundice and ultrasonography disclosed
      multiple common bile duct stones, cystic dilatation of the extrahepatic biliary
      tree and a mass in the right lobe of the liver. At operation, after a frozen
      section demonstrated cholangiocarcinoma, a common bile duct exploration, right
      hepatic lobectomy and hepato-jejunostomy were performed. They review the
      literature on the subject and stress the fact that hepatic tumors are associated
      with Caroli's disease in 7% of cases. Therefore, in these patients, when a
      stenosis of the biliary tree is found, multiple diagnostic manoeuvres are
      indicated in order to exclude the presence of malignancy.

PMID- 8290140
TI  - [The early diagnosis of colorectal tumors].

PMID- 8290139
TI  - [A new CO2 insufflator for laparoscopic surgery].

PMID- 8290141
TI  - [The repair of inguinal and/or crural hernias with giant Mersilene prostheses in
      the preperitoneal position].
AB  - The authors present 44 patients operated for hernias (inguinal and/or femoral)
      with a median pre-peritoneal approach positioning a mersilene mesh with Stoppa's
      technique. The results are very interesting considering that the hernias treated
      are all at high risk of recurrence. We had 4 complications (1 bleeding and 3
      wound infections) that were conservatively treated, no mortality at all. The
      follow-up was of 12 months (mean) and no recurrence was discovered.

PMID- 8290142
TI  - [The rational use of drains in surgery].
AB  - The authors report their clinical experience in 100 cases in which various kinds
      of drainage were used. They outline the best present techniques, when it is
      wished to apply this free drainage in the abdominal cavity, at the end of the
      operation.

PMID- 8290143
TI  - [An analysis of the surgical risk in elderly subjects with neoplasms of the large
      intestine. A follow-up of 102 consecutive cases].
AB  - Today surgeons find that they have to operate with increasing frequency on
      elderly patients suffering from colorectal cancer. This study examined 102
      patients with this pathology. The findings show that age alone is not a
      contraindication for surgery. On the contrary decisive negative factors include
      both concomitant pathologies and emergency surgery because it is not possible to
      correct any pre-existing imbalances before surgery. The overall mortality rate is
      9% of which 4% after emergency surgery. It is therefore possible to conclude that
      elderly patients can undergo radical surgery irrespective of age.

PMID- 8290144
TI  - [Cholecystectomy via laparoscopy in situs inversus totalis. A case report and
      review of the literature].
AB  - The authors report a case of symptomatic cholelithiasis in a patient with situs
      inversus totalis, in which the surgical treatment was performed by laparoscopy.
      They discuss the etiopathogenesis of this anomaly and malformations often
      associated, moreover related clinical and surgical problems. Finally, they
      describe operative technique stressing the real possibility to perform the
      operation by laparoscopy on condition that the surgeons have sufficiently
      experience of biliary and laparoscopic surgery.

PMID- 8290145
TI  - [Lumbar hernia of Grynfeltt's quadrilateral space. Apropos a case].
AB  - The authors discuss a case of Grynfeltt's quadrilateral lumbar hernia in an 85
      year-old patient. These rather rare hernias can be classified as Grynfeltt's
      hernias of the superior lumbar space, as Petit's inferior lumbar space and as
      diffused hernias concerning the whole hip. In our case this hernia was located in
      the superior lumbar space and it was delimited on the upper part by the 12th rib
      and by the serratus posterior-inferior muscle; in the lower part by the internal
      oblique muscle and by the lumbar quadratus muscle. Surgical treatment was
      effected by plastic surgery with synthetic material put in the extra-peritoneum
      space and fixed by serum-muscular stitches. Postoperative control effected after
      a month from the operation proves a good keeping of the plastic surgery
      reconstruction with total disappearance of the hernia.

PMID- 8290146
TI  - [Autotransfusion: its use in a case of spontaneous splenic rupture in non
      Hodgkin's lymphoma].
AB  - The article refers to autotransfusion experience in a patient affected by
      lymphoma (not Hodgkin type), who reached surgery for haemoperitoneum caused by
      the spontaneous rupture of the spleen. Considering the pathology, this method
      brought unpredictable variations in the hemochrome thus leading to a deep
      reflection on the limitations of the use of autotransfusion.

PMID- 8290147
TI  - [Splenic metastases of ovarian carcinoma].
AB  - A patient with ovarian carcinoma and splenic metastasis who underwent
      cytoreductive surgery is described. Since the patient had liver cirrhosis the
      authors hypothesize that the hepatic problem could have been a risk factor for
      splenic metastasis.

PMID- 8290148
TI  - [Intestinal occlusion due to a colonic lipoma. Apropos 2 cases].
AB  - Lipomas occur through the intestinal tract, from the hypopharynx to the rectum,
      the colon having the highest incidence, where lipomata are the commonest benign
      neoplasm after adenomata. Nevertheless they are uncommon. CASE REPORT. 1) A 68
      year-old man presented as an emergency with abdominal pain associated with bowel
      obstruction. He had a 2 to 3 month history of intermittent right-sided abdominal
      pain, constipation spontaneously resolved. At laparotomy there was a mass of the
      transverse colon, next hepatic flexure. A right hemicolectomy was performed. The
      patient made an uneventful recovery. Histologic examination showed a lipoma of
      the submucosal plane. 2) A 65-year-old man presented as an emergency with lower
      abdominal pain associated with a prolapsed rectal polyp. He had 1 month history
      of passing fresh blood per rectum. Ap ast colonoscopy revealed a large polypoid
      lesion in the descending colon. Transanal examination revealed a polypoid lesion
      with a maximum diameter of 4 cm, acting as an intussuseptum. Transanal
      polypectomy was performed. At laparotomy there was an intussuseptum of the
      descending colon into the rectum: a left hemicolectomy was performed. Histology
      showed the polyp to be a submucosal lipoma. DISCUSSION. Lipomas are the most
      common benign nonepithelial tumors of the colon. Lipomata of the large bowel are
      reported as incidental findings in 0.3-0.5% of cases in large series of
      autopsies. In the wall of the intestine most lie in the submucosal plane, less
      frequently they are found in the subserosal plane. The commonest site for
      symptomatic solitary large bowel lipoma is the ascending colon, including the
      caecum, followed by the transverse colon, including both hepatic and splenic
      flexure, descending colon, sigmoid colon and rectum. The peak incidence for
      lipomata of the large bowel is in fifth-sixth decade. Colonic lipomas are
      generally asymptomatic but occasionally patients may have intermittent crampy
      abdominal pain secondary to intussusception of a pedunculated lipoma or with
      intermittent fresh rectal bleeding. On barium enema lipomas appear circular,
      ovoid, well demarcated, and smooth. A barium enema showing a relatively
      radiolucent mass, caused by the radiolucency of fat, is suggestive of a lipoma.
      The water enema, with water as the contrast agent, accentuates the difference in
      density between a lipoma and surrounding tissues. Another characteristic feature
      of lipomas on barium enema is said to be their fluctuation in size and shape
      during the study: "squeeze sign". Lipomas of the large bowel can be seen,
      however, by colonoscopy. On computerized tomography scan the lipoma has a uniform
      appearance and density. In expert hands pedunculated and sessile lesions can be
      removed endoscopically, but often large bowel lipomata are treated on the basis
      of a presumptive malignant diagnosis with exploratory laparotomy. CONCLUSION.
      Colonic lipomas, although unusual, continue to present difficulties in the
      preoperative differentiation between malignant and benign colonic neoplasm. Two
      cases of colonic lipomas are reported.

PMID- 8290149
TI  - [Calculosis of the cystic duct].
AB  - The authors report on three cases of cystic duct syndrome, a fairly uncommon
      complication of cholelithiasis, consisting in migration of a large gallstone from
      the gallbladder to the common bile duct, resulting in the formation of a common
      cavity between cystic, hepatic and common bile ducts. They review the
      pathogenesis of this entity, as well as the diagnostic modalities best suited to
      a precise diagnosis. They stress that surgical therapy must be chosen on a case
      by case basis, trying to restore a functional extrahepatic biliary tree.

PMID- 8290150
TI  - [The indications and results in 313 liver transplants].
AB  - The authors report their experience on 313 liver transplantations performed in
      255 patients. In 51.7% the indication to liver transplant was the cirrhosis, post
      alcoholic in 39.5% and post-hepatitis in 24.1%. The global mortality was 34.9%
      (89/255) with an actuarial survival of 53% at 74 months. We registered 10 cases
      (3.2%) of arterial thrombosis and 5 cases (1.6%) complications of portal
      anastomosis.

PMID- 8290151
TI  - [The surgical treatment of hepatic echinococcosis and of its biliary
      complications].
AB  - The authors report the experience of 47 patients submitted to surgery for hepatic
      hydatidosis. Results from different therapeutic procedures are then compared.
      Finally, possible biliary complications of the hepatic echinococcosis and their
      surgical treatment are discussed.

PMID- 8290152
TI  - [The diagnostic procedure in deep venous thrombosis. The authors' experience].
AB  - Diagnostic flow chart of 101 patients admitted with suspected TVP between 1987
      and 1991 is discussed. In all of them Doppler cw and radionuclide venography with
      pulmonary scanning with albumin Tc 99 were performed. Since the 90's a triplex
      scanner was employed, usually after Doppler cw examination. Phlebography was
      considered as a golden backup. Pulmonary embolism was detected in 15% of patients
      and 2/3 were completely asymptomatic.

PMID- 8290153
TI  - [The emergency treatment of perforated colonic diverticula].
AB  - The authors report their experience of the treatment of 43 cases of perforated
      colonic diverticula. The operations were: 12 primary resections-anastomoses; 7
      resections-anastomoses with protective colostomy; 2 operations of suture and
      drainage; 22 Hartmann's resections. The authors believe that Hartmann's resection
      is the operation of first choice in cases of diffuse or stercoraceous
      peritonitis. This operation another the removal of the sick part of intestines
      without exposing the patient to the possible complications of an operation "at
      risk", and allows a late recanalization destitute of risk: in our experience 13
      cases of 22 (59%).

PMID- 8290154
TI  - [Myoid tumors of the stomach. Our experience].
AB  - The authors analyse the incidence of myoid tumours of the stomach in comparison
      to bowl cancer as a whole and identify the different anatomopathological
      varieties (benign leiomyoma, leiomyosarcoma and Martin-Stout's bizarre
      leiomyoma). Symptoms are usually subtle and development slow: important factors
      are the site of onset (antro-pyloric in 60% of cases, body 25% and cardias 15%),
      the type of tumour growth (intra- or extraluminal or mixed) and tumour size which
      may sometimes be considerable. Four categories of patients are identified on the
      basis of symptoms shown: a) asymptomatic (chance diagnosis), b) aspecific (vague
      symptoms such as epigastralgia, dyspepsia, ecc.), c) symptomatic (presence of
      abdominal mass, chronic anemia, ecc.), d) complicated (onset of complications the
      most frequent of which is acute hemorrhage). The clinical data reported here
      refers to 4 patients (3 males and 1 female) aged between 53 and 75 years old. In
      one case diagnosis was made by chance, in 2 cases diagnosis followed acute
      hemorrhage of the upper digestive tract, and in the case of the woman clinical
      controls began following the finding of a voluminous abdominal mass. Diagnosis
      was based on traditional radiology and EGDscopy, as well as ultrasonography and
      CT. Treatment was surgical in all cases (two enucleations of the lesion and two
      atypical gastric resections). In the light of the authors' personal experience
      and data reported in the literature, the discussion focuses attention on the
      problems of diagnosis and therapy, in particular the various options facing the
      surgeon in the form of operating tactics.

PMID- 8290155
TI  - [Inguinal hernioplasty by a modified Shouldice technic. Our experience with 350
      treated cases].
AB  - A statistical analysis of 340 patients operated between 1986 and 1991 for
      inguinal hernia using the Shouldice procedure are reported by the authors. The
      majority of patients (60%) treated was between 45 and 65 years old. Two-hundred
      eighty-one (82%) were controlled with a mean follow-up of 30 months (range 1-6
      years) and was executed with physical examination and a medical questionnaire
      looking for recurring factors of risk. Hundred-twenty-eight patients (45% of
      controls) were at the high risk, nevertheless hernia recurrences were not
      noticed. Postoperative course was uncomplicated in 93% of patients. Early or late
      loco-regional complications had an incidence of 7%. Local infections and edema
      were reported in 10 of 22 patients. Acute urinary retention, cephalalgia and
      hypotension correlated with an anesthesiologic method had an incidence of 5% (17
      cases). There were no deaths was pulmonary embolisms. A review of literature was
      performed and compared with our work. From experience in our Division,
      Shouldice's hospital technique had a high reliability compared to methods
      utilized in the previous ten years (Bassini, McNealy, Postemskj, Mugnai-Ferrari),
      in terms of recurrences.

PMID- 8290156
TI  - Discrepancies between myocardial perfusion and free fatty acid metabolism in
      patients with hypertrophic cardiomyopathy.
AB  - To test the hypothesis that there are discrepancies between 201Tl- and 123I-beta
      methylpentadecanoic acid (BMIPP) distribution in the left ventricular myocardium
      and to assess whether BMIPP is a useful tracer agent for the assessment of left
      ventricular function in hypertrophic cardiomyopathy (HCM), myocardial single
      photon emission computed tomography (SPECT) was performed with 201Tl and BMIPP in
      five normal subjects and 12 patients with asymmetric septal hypertrophy. Tracer
      uptake in the left ventricular myocardium was scored using a four-point grading
      system. A homogenous distribution of the tracer with no discrepancy between 201Tl
      and BMIPP uptake in the left ventricular myocardium was observed in each normal
      subject. In contrast, BMIPP uptake was reduced compared to 201Tl in 58 segments
      (40%) of the 144 myocardial segments in patients with HCM. Such discordant BMIPP
      uptake was observed in 15 segments (42%) of the septal segments, in 19 segments
      (53%) of the anterior segments, in eight segments (22%) of the lateral segments,
      and in 16 segments (44%) of the inferior segments. There was no significant
      correlation between 201Tl perfusion score and left ventricular ejection fraction,
      whereas there was a significant correlation between BMIPP perfusion score and
      left ventricular ejection fraction (r = 0.748; P < 0.01). The results indicated
      that there were discrepancies between 201Tl and BMIPP uptake in a significant
      proportion of myocardial segments, suggesting the impairment of fatty acid
      metabolism and that BMIPP is a useful tracer agent for the assessment of left
      ventricular function in hypertrophic cardiomyopathy.

PMID- 8290157
TI  - Role of radionuclide venography in the detection of proximal deep vein
      thrombosis: a prospective comparative study.
AB  - The role of radionuclide techniques in the investigation of thromboembolic
      disease has been re-evaluated. Forty-eight patients suspected of having embolic
      lung disease (PE) or deep venous thrombosis (DVT) were studied prospectively and
      investigated with radionuclide venography and ventilation/perfusion lung
      scintigraphy. Thirty-two also underwent contrast venography and peripheral 99Tcm
      labelled red blood cell scintigraphy. Both radionuclide techniques were compared
      to each other and against the 'gold-standard'. The overall agreement and
      disagreement rates were 89 and 11% for radionuclide venography and 88 and 12% for
      radionuclide blood pool venography. The overall sensitivity and specificity were
      90 and 73% for radionuclide venography and 88 and 82% for radionuclide blood pool
      venography. The blood pool technique did not perform better than radionuclide
      venography which was valuable in the detection of DVT and confirmation of PE.
      Radionuclide venography appears useful especially in patients suspected of having
      PE and DVT.

PMID- 8290159
TI  - Evaluation of various methods of 99Tcm-human immunoglobulin preparation in
      scintigraphic detection of infection.
AB  - Radiolabelled human immunoglobulin (HIG) scintigraphy has been recognized as a
      reliable modality for the localization and evaluation of pyogenic infection in
      humans. Four methods of labelling HIG with 99Tcm developed by the Institute of
      Nuclear Energy Research of Taiwan are: (1) using ascorbic acid (ASC) for direct
      labelling of HIG (ASC-HIG); (2) using diethylenetriamine pentaacetate (DTPA) as a
      bifunctional chelate (DTPA-HIG); (3) using 2-iminothiolane (IM) for modified
      protein (IM-HIG); (4) using the avidin-biotin system (AVI-BIO-HIG). Our study
      assessed these four preparations in the scintigraphic detection of infections.
      Staphylococcus aureus was injected intramuscularly into the left thighs of
      rabbits. Two days later, when active inflammation developed, 5 mCi 99Tcm-HIG was
      given intravenously; scintigraphy was performed at 1, 4 and 18 h. The
      accumulation of 99Tcm DTPA-HIG was the most prominent among the four preparations
      at the site of infection. It is concluded that 99Tcm labelling of HIG using DTPA
      as a bifunctional chelate may be the optimal labelling method for detecting
      infection.

PMID- 8290158
TI  - Viability and biodistribution of 68Ga MPO-labelled human platelets.
AB  - The viability and biodistribution of 68Ga-mercaptopyridine-N-oxide (MPO)-labelled
      autologous platelets was studied in 10 patients. The average platelet labelling
      yield was 36 +/- 12% and injected activity was 2.0 +/- 0.9 mCi 68Ga. The %
      activity in platelets per ml whole blood was 64 +/- 20% at 15 min-1.0 h
      postinjection and 76 +/- 14% at 2-4h. The average recovery of platelets (%
      injected platelets circulating in peripheral blood) was 31 +/- 21% at 15 min-1 h
      and 39 +/- 20% at 2-4 h. The positron emission tomographic (PET) images showed
      high circulating vascular background. Two patients had technically inadequate
      scans, and six were false negative due to high blood background. One patient with
      a massive pulmonary embolus occurring 24 h prior to scanning had marked uptake of
      68Ga platelets in a large clot in the superior branch of the right main pulmonary
      artery. A second patient, with 68Ga platelets circulating during angioplasty of a
      left posterior tibial artery stenosis, had intense uptake in the lesion shown on
      the PET scan obtained 4 h following the procedure. These results indicate good
      viability of 68Ga-MPO-labelled autologous human platelets, but poor visualization
      of clots by PET imaging, due to the high blood background at early times.

PMID- 8290160
TI  - Multidose use of exametazine for leukocyte labelling: a new approach using tin
      enhancement.
AB  - Reconstituted exametazime is inherently unstable due to the rapid oxidation of
      the small amount (7.6 micrograms) of stannous chloride present in the kit. A
      novel approach has been used to improve the shelf-life of reconstituted
      exametazime based on the premise that tin lost through oxidation should be
      replaced by further amounts of tin. Freshly prepared stannous solution, 0.1 ml
      (0.66 microgram Sn2+), was mixed with 0.3 ml (25 micrograms) exametazime solution
      followed by 400-500 MBq pertechnetate. Mixed leukocytes from 50 ml of patients'
      blood were labelled with 99Tcm-exametazime which had been prepared by the tin
      enhancement. One hundred and fourteen patients were investigated. The median
      labelling efficiency was 72%, range 30-96%. The exametazime had been
      reconstituted up to 5 months previously. Because of the small volumes of the
      exametazime solution used, up to 15 doses for leukocyte labelling could be
      prepared from one vial.

PMID- 8290162
TI  - Re: Question of the month: medical audit 3.

PMID- 8290161
TI  - Radiolabelling and reinfusion of blood cells.

PMID- 8290163
TI  - 201Tl as a tumour-localizing agent.

PMID- 8290164
TI  - Radiolabelling and reinfusion of blood cells.

PMID- 8290165
TI  - Thallium myocardial perfusion tomography using intravenous dipyridamole combined
      with maximal dynamic exercise.
AB  - Exercise thallium imaging is effective and provides information on exercise
      tolerance and symptoms, but is less sensitive if exercise is submaximal. When
      dipyridamole alone is used for such patients, the exercise parameters are lost
      and high background uptake results. This study examines dipyridamole combined
      with maximal exercise, to capitalize on the strengths of both techniques.
      Thallium tomography was performed in 122 patients with dipyridamole (group 1),
      exercise (group 2), or dipyridamole with maximum exercise (group 3). In patients
      with coronary artery disease, thallium tomography was abnormal in 92, 93 and 95%
      (P = ns), with reversible ischaemia in 82, 81 and 84% (P = ns) in the three
      groups, respectively. Among patients in groups 2 and 3 who exercised
      submaximally, detection of individual arterial stenoses was improved in group 3
      (P < 0.05) and larger defects were found (2.4 versus 4.2 segments, P < 0.01). In
      group 3, no serious complications occurred and fewer vasodilatory side effects
      were seen than in group 1 (P < 0.01). The heart to splanchnic count ratio in
      groups 2 and 3 (1.61 versus 1.65, P = ns) was significantly greater than in group
      1 (1.28, P < 0.0001). Compared with exercise alone, additional dipyridamole
      improved diagnostic accuracy in patients with limited exercise potential.
      Compared with dipyridamole alone, additional exercise provided useful exercise
      information, reduced vasodilatory side effects and improved scan quality.
      Combined dipyridamole and exercise stress is safe, and could be used routinely,
      but a larger study is required to establish if there is an overall diagnostic
      improvement.

PMID- 8290166
TI  - Evaluation of coronary artery disease extent using 99Tcm-sestamibi: comparison of
      dipyridamole versus exercise and of planar versus tomographic imaging.
AB  - The aim of this study was to compare the reliability of 99Tcm-sestamibi
      myocardial scintigraphy for the assessment of coronary artery disease extent
      using two different stresses (exercise and dipyridamole) and imaging techniques
      (planar versus single photon emission tomography, SPET) in a patient population
      of 20 subjects, all also studied with coronary angiography. The agreement of
      exercise and dipyridamole was good for the visual uptake score (planar kappa =
      0.71, SPET kappa = 0.64) and for abnormal segment detection (planar and SPET both
      kappa = 0.76). For the recognition of the individual diseased vessel, the results
      of exercise and dipyridamole planar scans were equal (sensitivity 49%,
      specificity 90%, accuracy 63%); those of exercise and dipyridamole SPET were also
      similar and were both better than the related planar data (sensitivity 79% and
      74%, P < 0.005 and < 0.02, respectively, versus planar; specificity 95% and 100%;
      accuracy 85 and 83%, P < 0.001 and < 0.02 versus planar). Both stresses and
      imaging techniques were less sensitive in cases of mild (50 to 70%) obstructions.
      In conclusion, exercise and dipyridamole appear equally effective stresses for
      99Tcm-sestamibi scintigraphy; with both of them, however, SPET allows
      significantly better results than planar imaging and therefore should be
      recommended.

PMID- 8290167
TI  - Satellite PET and lung cancer: a prospective study in surgical patients.
AB  - Positron emission tomography (PET) appears to be an innovative method for imaging
      the proliferative activity of malignant tissue, in particular by means of 18F
      labelled fluorodeoxyglucose (FDG). The potential role of PET scanning was
      investigated in a satellite centre as an adjunct to conventional methods for
      estimating the likelihood of pulmonary malignancy. Therefore the sensitivity of
      detection of lung cancer in candidates was determined prior to exploratory or
      therapeutic thoracotomy by FDG PET imaging. The study involved 36 patients with
      abnormal chest roentgenogram and suspected lung cancer who were due for
      thoracotomy. The PET scans were evaluated qualitatively and semiquantitatively.
      Pulmonary malignancy was found in 31/36 patients and 29 had a focal increase in
      FDG pulmonary uptake. Benign pulmonary lesions were found in 5/36 patients, three
      of whom had a negative PET scan. The sensitivity of detection of lung cancer by
      FDG PET was therefore 93.5%. Bayesian study shows that FDG PET could be the most
      useful method in a population with a low prevalence of lung cancer. As
      illustrated by our study, a simple FDG PET scanning protocol in a satellite PET
      centre could provide adequate clinical information and help in deciding
      subsequent patient management.

PMID- 8290168
TI  - Somatostatin receptor imaging in small cell lung cancer using 111In-DTPA
      octreotide: a preliminary study.
AB  - Small cell lung cancer is a common and aggressive disease. Combined multiagent
      chemotherapy and radiotherapy can improve short-term prognosis, but long-term
      prognosis remains dim. Somatostatin receptors have been identified on the
      cellular surface of subsets of this cancer and may be associated with less
      aggressive evolution. Moreover, medical therapy with somatostatin analogues holds
      promise for neoplastic growth control. Planar scintigraphy has been performed in
      15 patients with histologically proven small cell lung cancer at 4 and 24 h after
      the intravenous (i.v.) injection of 185 MBq 111In-octreotide (Octreoscan, BYK
      Gulden). No short-term adverse effects were recorded; tumour uptake of the
      radiopharmaceutical was observed in 13 patients at 4 h and in 12 patients at 24 h
      suggesting more extensive disease than apparent by computed tomography (CT). It
      is highly likely that the 24 h uptake reflects the presence of somatostatin
      receptors on the tumour. Previous chemotherapy does not seem to play a key role
      in tumour visualization. 111In-octreotide is a suitable radiopharmaceutical for
      in vivo evaluation of somatostatin receptor status of small cell lung cancer.
      Quantitative scintigraphic methods are needed to investigate nonspecific binding
      and receptor kinetics.

PMID- 8290169
TI  - Evaluation of hypertensive patients with a solitary kidney using captopril renal
      scintigraphy with 99Tcm-MAG3.
AB  - The study aimed to evaluate the safety and reliability of captopril renal
      scintigraphy (CRS) for diagnosing functionally significant renal artery stenosis
      (RAS) in hypertensive patients with a solitary kidney. Radionuclide studies were
      carried out using 100 MBq 99Tcm-mercaptoacetyl triglycine (MAG3), 1 h after
      administration of 50 mg captopril, and repeated in baseline condition when
      abnormalities were observed in the provocative study. Scintigraphic diagnosis of
      RAS was based on analysis of captopril-induced changes of the radiorenographs.
      Overall, 12 patients with a solitary kidney were investigated, and scintigraphic
      results compared to angiographic findings. All five patients with positive CRS
      showed an RAS > 50%, whereas only one of the seven patients with negative CRS was
      affected by RAS. A significant fall in mean arterial pressure was recorded after
      captopril administration (123 +/- 12 mm Hg before versus 108 +/- 11 after), but
      no serious side effects were observed. Our results demonstrate that captopril
      induced modifications of the renogram could effectively be used to diagnose the
      presence of RAS. Captopril renal scintigraphy may therefore be suggested as a
      reliable and safe noninvasive approach to evaluate hypertensive patients with a
      solitary kidney.

PMID- 8290170
TI  - A pilot study of flaccid penile blood flow patterns in normal subjects and
      patients with erectile dysfunction.
AB  - Dynamic penile scintigraphy was performed using 99Tcm-labelled autologous
      erythrocytes in five normally potent volunteers and 22 patients with erectile
      dysfunction including 11 patients with psychogenic and 11 patients with
      vasculogenic impotence (four arteriogenic, three venogenic, three arteriogenic
      and venogenic, one arteriogenic and neurogenic). Penile radioactivity changes in
      the flaccid state were monitored by a gamma camera for 60 min after injection of
      the radionuclide. The penile time-activity curves of the normal controls
      characteristically showed secondary pulses of increased activity of variable
      amplitude, duration and frequency, consistent with phasic increase in penile
      blood pool. This normal rhythmic pattern was impaired in patients with penile
      arterial insufficiency whereas a blunted pattern was seen in most patients with
      functional impotence as well as in patients with nonarteriogenic organic
      impotence with a psychological overlay. This study provides new insights into the
      flaccid penile circulatory physiology, which may contribute to our understanding
      of the pathophysiology of erectile dysfunction. In arteriogenic subjects, the
      impaired response may be attributable to an inadequacy of penile arterial inflow
      as well as secondarily due to the resultant sinusoidal dysfunction subsequent to
      penile ultrastructural damage due to an altered nutritive environment. Increased
      adrenergic activity in patients with psychogenic impotence may be responsible for
      the observed deviation from the normal pattern.

PMID- 8290171
TI  - The limitations of posterior view ventilation scanning in the diagnosis of
      pulmonary embolism.
AB  - In the diagnosis of pulmonary embolism some centres using 133Xe for comparison
      with multiple view 99Tcm perfusion images perform only single-breath posterior
      view ventilation scans. The purpose of this study was to test the reliability of
      the posterior view ventilation scan in the detection of lobar and segmental
      defects in ventilation. Occluding balloon catheters were placed in lobar and
      segmental bronchi during fibreoptic bronchoscopy to produce defects of known
      anatomical location and size in normal volunteers. Subjects breathed 81Krm/air
      during the occlusions and images were acquired in the posterior,
      posterior/oblique and lateral projections. The posterior view images were
      classified by three experienced nuclear medicine physicians as normal or
      abnormal. If abnormal, the observers were asked to state which lobe or segment
      was involved. Segmental defects were missed in 28% of scan readings. Segmental
      defects were detected but incorrectly sited in 50% of readings and correctly
      sited in only 22% of readings. The posterior view scan with a defect involving
      the entire lingula was judged to be normal by all observers. Defects involving
      the right and left lower lobes were underestimated. We conclude that ventilation
      scanning techniques that assess the distribution of ventilation in the posterior
      view alone are unreliable in the detection of segmental and lobar defects, and
      are likely to increase the false positive rate in the diagnosis of pulmonary
      embolism.

PMID- 8290172
TI  - Lung scan reports: interpretation by clinicians.
AB  - A questionnaire was sent to 217 consultant physicians in Scotland who were likely
      to encounter pulmonary embolism (PE) in their daily practice. Replies were
      received from 194 (89%). Only 34% of physicians understood that a normal lung
      scan made PE highly unlikely, while 65% considered a low probability scan
      equivalent to an uncertain diagnosis. This pattern of interpretation of lung scan
      reports was confirmed by a question on post-test management. After a normal lung
      scan report, 31% of physicians were uncertain about the diagnosis and this
      uncertainty increased to 37% for a low probability scan report. This survey has
      shown misunderstanding by a significant number of physicians of the risk of PE
      indicated by normal and low probability lung scan reports. It underlines the need
      for individuals reporting the test to provide informed guidance for clinical
      staff following ventilation/perfusion (V/Q) imaging. It may point in addition to
      a need for a more easily understood style of reporting of lung scans.

PMID- 8290173
TI  - Extending the life of a 99Tcm generator: a simple and convenient method for
      concentrating generator eluate for clinical use.
AB  - 99Tcm-pertechnetate can conveniently be concentrated 5-20-fold by passing up to
      20 ml through a sequence of two (or three) disposable columns, one (or two) to
      remove chloride and one to concentrate the pertechnetate for subsequent elution
      with a small volume of saline. This procedure is useful for utilizing eluates
      with low radioactive concentration in applications that require high radioactive
      concentration.

PMID- 8290174
TI  - Comparative myocardial imaging in the baboon with 123I-labelled ortho and para
      isomers of 15-(iodophenyl)pentadecanoic acid (IPPA).
AB  - The use of various animal models for researching radioiodinated fatty acid
      cardiac metabolism has been proven to be risky. This fact is here confirmed in
      the higher primate. Six baboons were injected on different occasions with 123I
      labelled para and ortho isomers of 15-(iodophenyl) pentadecanoic acid (123I-pPPA
      and 123I-oPPA, respectively) for dynamic scintigraphy, followed by a Na123I
      injection at 30 min for blood background correction. Times for maximum myocardial
      tracer uptake (Tmax), and half-times of clearance (two phases T1/2(1) and
      T1/2(2)) from biexponential fitting of the time-activity curves proved
      statistically not different for pPPA and oPPA (P > 0.05). A repeat study at a
      later stage on the same baboons included pretreatment (2 h pretracer) with a
      carnitine palmitoyl transferase I inhibitor (Extomoxir; 10 mg kg-1) to block
      myocardial beta-oxidation. Time-activity curves with Tmax, T1/2(1) and T1/2(2)
      followed as above and were compared to the initial uninhibited values. Blocking
      of the carnitine shuttle was demonstrated by significantly increased retention of
      123I-pPPA and 123I-oPPA. Thus both the tracers are beta-oxidized in the baboon
      myocardium, which is different in rat and human studies. In rats both isomers
      wash out from the myocardium, but 123I-oPPA is not metabolized. In humans the
      123I-pPPA is beta-oxidized as with rats, but the 123I-oPPA is retained in the
      lipid pool of the myocardium. Simultaneous multiple consecutive gated blood pool
      studies (six of 1 min each) provided encouraging perfusion-related, background
      corrected images, and corresponding uptake information.

PMID- 8290175
TI  - Relative risks and benefits of long-term estrogen replacement therapy: a decision
      analysis.
AB  - OBJECTIVE: To evaluate the relative risks and benefits of exogenous estrogen use
      among women entering the climacteric and to consider estrogen use for relief of
      symptoms or prevention of disease. METHODS: Decision analysis was used to assess
      the value of estrogen replacement therapy in a hypothetical cohort of 10,000
      women assumed to be age 50 years; health outcomes were extrapolated to age 75.
      Risk ratios for mortality and morbidity of health outcomes associated with the
      use of estrogen replacement therapy were based on longitudinal studies reported
      in the literature. RESULTS: Estrogen use for 25 years would decrease fatal
      coronary heart disease events by 48% (567 cases), decrease deaths from hip
      fracture by 49% (75), increase deaths from breast cancer by 21% (39), and
      increase deaths from endometrial cancer by 207% (29 excess deaths). On balance,
      25 years of estrogen replacement therapy in a cohort of 10,000 women would
      prevent 574 deaths. Further, women using estrogens for 25 years would gain 3951
      quality-adjusted life years compared with women not using estrogens. Sensitivity
      analysis suggests that the benefits of estrogen replacement therapy outweight the
      risks under most assumptions. CONCLUSION: In a hypothetical, population-based
      analysis, the health benefits of postmenopausal estrogen replacement exceed the
      health risks incurred. Nevertheless, clinicians must still evaluate each
      individual's risks and needs.

PMID- 8290176
TI  - The independent effects of exercise and estrogen on lipids and lipoproteins in
      postmenopausal women.
AB  - OBJECTIVE: To assess the effects of a moderate exercise program with and without
      oral estrogen replacement on levels of lipids and lipoproteins in postmenopausal
      women. METHODS: One hundred one postmenopausal women were randomized into four
      groups: control or sedentary (N = 20), exercise alone (N = 25), estrogen
      replacement using 0.625 mg conjugated equine estrogen (N = 28), and exercise
      supplemented with conjugated equine estrogen (N = 28). The exercise groups were
      placed on a moderate exercise program. Following baseline testing, each group
      returned at 3 and 6 months for cardiorespiratory fitness testing and serum lipid
      and lipoprotein profiles. RESULTS: We found a significant decrease in systolic
      blood pressure (P < .05) in all treatment groups. The maximum oxygen uptake
      increased by 9.0 and 7.8% in the exercise and conjugated equine estrogen/exercise
      groups, respectively, compared to the other groups (P < .05). These responses
      were seen at both 3 and 6 months. Total exercise time (time spent on the
      treadmill until exhaustion during testing) significantly increased in the
      exercise group by 21% (P < .01). Exercise alone was associated with significant
      decreases in total cholesterol (5.2%, P < .05), triglycerides (2%, P < .05), and
      low-density lipoprotein (LDL) cholesterol (10%, P < .01), and a significant
      increase in the high-density lipoprotein (HDL) cholesterol-LDL ratio (17.2%, P <
      .01). Significant changes were noted in these values, as well as increases in HDL
      cholesterol (16 and 14.8%; P < .01) and apolipoprotein A1 (25.6 and 26.5%; P <
      .001) in the conjugated equine estrogen and conjugated equine estrogen/exercise
      groups, respectively. However, there were no differences in the changes observed
      in the conjugated equine estrogen groups with versus without exercise. No direct
      correlation was seen between measures of exercise performance and the changes
      seen in lipids and lipoproteins. CONCLUSIONS: Estrogen therapy alone had the
      greatest beneficial effect on lipids and lipoproteins. Exercise alone resulted in
      a significant reduction in cholesterol, triglycerides, and LDL cholesterol, and
      an increase in the HDL-LDL ratio. However, combined conjugated equine estrogen
      and exercise did not demonstrate an added improvement in lipid metabolism.
      Physical fitness levels increased in the exercise groups, but not in the control
      group or the estrogen-alone treated women.

PMID- 8290177
TI  - Quantitative and qualitative changes in lipids, lipoproteins, apolipoprotein A-I,
      and sex hormone-binding globulin due to two doses of conjugated equine estrogen
      with and without a progestin.
AB  - OBJECTIVE: To determine whether the quantitative and qualitative effects on
      lipoproteins differ between two doses of conjugated equine estrogen before and
      after progestin administration. METHODS: We randomized 103 postmenopausal women
      into a control group and into two groups receiving either 0.625 mg or 1.25 mg of
      conjugated equine estrogen for 4 months and then the same estrogen dose plus
      cyclic medroxyprogesterone acetate for 8 months. RESULTS: Both estrogen doses
      similarly lowered (P < .01) low-density lipoprotein (LDL) cholesterol and raised
      (P < .01) high-density lipoprotein (HDL) cholesterol, apolipoprotein A-I,
      triglyceride levels of all lipoproteins, and sex hormone-binding globulin
      capacity. Cyclic addition of the progestin reduced HDL cholesterol (P < .01) and
      apolipoprotein A-I (P < .05), but not LDL cholesterol in either estrogen group. A
      greater lowering of HDL cholesterol (P < .05) in response to the progestin was
      seen with the 0.625-mg dose of estrogen. Estrogen-induced triglyceride enrichment
      of HDL and LDL was not reversed by the progestin. CONCLUSION: The only
      significant quantitative difference in lipoprotein levels between the doses of
      conjugated equine estrogen before or after administration of medroxyprogesterone
      acetate was a greater decline in HDL cholesterol levels with the lower dose after
      4 months of the progestin. This difference was not sustained over time. There
      were no differences between doses in the estrogen-induced triglyceride enrichment
      of lipoproteins, and these qualitative changes were not affected by the
      progestin.

PMID- 8290178
TI  - Changes in collagen composition and cross-links in bone and skin of osteoporotic
      postmenopausal women treated with percutaneous estradiol implants.
AB  - OBJECTIVE: To determine the effects of percutaneous estradiol (E2) implants on
      the collagen composition and maturity in the bone and skin of osteoporotic
      postmenopausal women. METHODS: Sixteen postmenopausal women with low bone mineral
      density were treated for 1 year with 75-mg E2 implants. Iliac crest bone and skin
      biopsies were analyzed for collagen content and collagen cross-links before
      treatment and at 1 year. Dual energy x-ray absorptiometry of the lumbar spine and
      proximal femur was also performed before and after 1 year of therapy. RESULTS:
      The cortical bone showed a significant increase in the mature cross-links of both
      hydroxylysylpyridinoline (P < .01) and lysylpyridinoline (P < .01), with a
      significant reduction in the percentage of collagen (P < .001). The pattern was
      similar in trabecular bone, with lysylpyridinoline increasing significantly (P <
      .05). The skin exhibited a significant reduction in the immature cross-link
      hydroxylysinonorleucine (P < .01), but no significant change in the percentage of
      collagen content or the mature cross-link histidinohydroxylysinonorleucine. The
      median increases in bone density were 11.5% at the spine and 4.34% at the total
      hip. The median post-treatment serum E2 level was 639 pmol/L. CONCLUSIONS: Bone
      mineral density increased at all the sites measured in the spine and proximal
      hip. The quality of the collagen within the transiliac biopsies had matured in
      that the concentration of the mature collagen cross-links had increased. These
      findings support a reduction in the turnover of bone collagen following estrogen
      replacement therapy. More important, the formation of a more mature collagen
      fiber should help to reduce the risk of future bone fracture.

PMID- 8290179
TI  - The temporal relation between the urine LH surge and sonographic evidence of
      ovulation: determinants and clinical significance.
AB  - OBJECTIVES: 1) To define the temporal relation between self-detection of the
      urine LH surge and sonographic evidence of ovulation, 2) to identify clinical
      factors that affect this interval, and 3) to determine whether differences in the
      day of sonographic detection of ovulation could potentially influence pregnancy
      rates during timed supracervical insemination cycles. METHODS: Two hundred sixty
      nine cycles in 145 women treated in an infertility center were analyzed. The
      subjects were referred for urine LH-timed supracervical insemination and were
      managed prospectively by protocol, including transvaginal sonographic
      confirmation of ovulation. Unstimulated and clomiphene citrate cycles were
      studied. RESULTS: Sonographic evidence of ovulation was detected by the first day
      after the urine LH surge (day +1) in 95 cycles (35%, 95% confidence interval [CI]
      29-41) and not until day +2 in 165 cycles (61%, 95% CI 55-67). Further analyses
      indicated that cycles with two or more ovulations were associated with a
      significantly greater percentage of cases in which ovulation was not demonstrated
      until day +2 (81%, 95% CI 76-86) compared with mono-ovulatory cycles (52%, 95% CI
      46-58) (P < .001). Multivariate analysis revealed that the day of sonographic
      detection of ovulation was linked with clinical pregnancy rates during these
      insemination cycles (P < .05). CONCLUSIONS: A substantial number of women,
      especially those with multiple ovulations, will not demonstrate sonographic
      evidence of ovulation until the second morning after detection of the urine LH
      surge. This temporal relation may exert an impact on pregnancy rates during
      supracervical insemination cycles.

PMID- 8290180
TI  - Exogenous gonadotropin therapy in World Health Organization groups I and II
      ovulatory disorders.
AB  - OBJECTIVE: To analyze cumulative conception rates and the prognostic factors
      influencing them during exogenous human menopausal gonadotropin (hMG) therapy for
      World Health Organization (WHO) group I or II ovulatory disorders. METHODS: A
      retrospective review was conducted of 468 treatment cycles in 146 women with
      ovulatory disorders refractory to conventional therapy. Cumulative conception
      rates were calculated, and the effects of diagnostic group, age, gravidity, and
      duration of infertility were examined using the Cox proportional hazards model.
      RESULTS: The cumulative proportion pregnant following six hMG cycles in WHO group
      I (0.89) was significantly greater than in the hyperandrogenic subgroup of WHO
      group II (0.30) (95% confidence interval [CI] 0.2-0.7, P = .006) or the luteal
      phase defect subgroup (0.35) (95% CI 0.07-0.6, P = .02). Conception rates in WHO
      group I did not differ significantly from those in the normoandrogenic oligo
      ovulatory subgroup of WHO group II (0.63) (95% CI 0.3-1.3, P = .6). Conception
      rates were not influenced by duration of infertility or primary versus secondary
      infertility. Women 35 years or older had significantly lower conception rates
      than those aged 27 years or less (P = .04, hazard ratio 0.3, 95% CI 0.1-0.8).
      CONCLUSIONS: Cumulative conception rates following exogenous gonadotropin therapy
      for women with refractory ovulatory disorders were both diagnosis- and age
      dependent. Treatment with hMG approximated or surpassed normal fertility rates in
      women with WHO group I and normoandrogenic WHO group II oligo-ovulation, but was
      significantly less successful at correcting the underlying defect in women with
      hyperandrogenic anovulation and luteal phase defects.

PMID- 8290181
TI  - Anal and cervical human papillomavirus infection and risk of anal and cervical
      epithelial abnormalities in human immunodeficiency virus-infected women.
AB  - OBJECTIVE: To determine the prevalence of anal and cervical infection with human
      papillomavirus (HPV) and cytologic abnormalities and to examine the relation
      among HPV infection, cytologic abnormalities, and human immunodeficiency virus
      (HIV) serostatus. METHODS: Anal and cervical Papanicolaou tests, HPV dot blot
      tests, and polymerase chain reaction (PCR) tests for HPV were performed
      concurrently in a cross-sectional study of 114 women enrolled in a community
      based study of HIV infection. RESULTS: Cervical HPV infection was associated with
      HIV serostatus by both dot blot (odds ratio [OR] 4.2, 95% confidence interval
      [CI] 1-25) and PCR (OR 8.9, 95% CI 3.2-27). Anal HPV infection was twice as
      frequent as cervical and also was associated with HIV by dot blot (OR 2.5, 95% CI
      0.9-7) and PCR (OR 2.6, 95% CI 1.03-6.8). Eleven percent (11 of 96) of cervical
      cytologies were abnormal and were associated with HIV (OR 6.1, 95% CI 1.2-60.5).
      Fourteen percent (15 of 109) of anal cytologies were abnormal and were associated
      with HIV (OR 3.4, 95% CI 0.9-15.5). Among HIV-seropositive women, epithelial
      abnormalities were associated with lower mean CD4+ cell counts when HPV DNA was
      detected by dot blot at either the cervix (P = .04) or anus (P = .009).
      Independent predictors for cervical epithelial abnormalities were HPV DNA
      positivity by dot blot (OR 32.1, 95% CI 2.9-353.9) and positive HIV serostatus
      with CD4+ cell count below 250 cells/mm3 (OR 126.8, 95% CI 7.5-2132.6).
      CONCLUSIONS: Human papillomavirus-associated epithelial abnormalities are
      associated with immune suppression among HIV-infected women. Anal HPV infection
      and disease is at least as common as cervical infection and disease among HIV
      seropositive women.

PMID- 8290182
TI  - Anal human papillomavirus infection and squamous neoplasia in patients with
      invasive vulvar cancer.
AB  - OBJECTIVE: To test the hypothesis that women with invasive vulvar cancer are at
      high risk of developing human papillomavirus (HPV)-associated anal squamous
      neoplasia. METHODS: Forty women (median age 54.5 years; range 25-86) who were
      being treated or had been treated for invasive vulvar cancer and who had not had
      radiotherapy to the pelvis or anogenital region underwent anal microendoscopy and
      biopsy. A second group of 80 women who were similar in age to the study group and
      had no history of anogenital HPV infection or neoplasia formed the control group.
      The polymerase chain reaction was used to detect HPV 16 DNA in the vulvar and
      anal tissue samples from 33 patients in the study group and in the anal biopsies
      of all controls. RESULTS: A histologic diagnosis of anal HPV infection or
      squamous neoplasia was made in 19 of 40 biopsies (47.5%) in the study group.
      These diagnoses consisted of one HPV, two anal squamous intraepithelial lesions
      (SIL) grade I, 15 and SIL grade III (four of which were associated with invasive
      anal cancers), and one invasive cancer in the absence of anal SIL. Human
      papillomavirus 16 DNA was detected in 16 of 33 (48.5%) of anal and 25 of 33 (75%)
      of vulvar biopsies. In addition, HPV 16 was detected in both the anal and vulvar
      samples in 13 of 16 cases (81%) of anal SIL III and invasive anal squamous
      cancer. No evidence of anal SIL was found in the controls, and HPV 16 DNA was
      identified in only 11 (13.7%) of the anal biopsies in this group. CONCLUSIONS:
      This study provides further evidence for the etiologic relation between genital
      and anal squamous neoplasia. Furthermore, it shows that women with vulvar cancer
      are at high risk of having or developing HPV-associated anal neoplasia,
      particularly in younger patients (P = .0006; 95% confidence interval 12-34).
      Routine anal examination should be performed in patients with invasive vulvar
      cancer.

PMID- 8290183
TI  - Transvaginal ultrasonographic diagnosis of bladder-wall invasion in patients with
      cervical cancer.
AB  - OBJECTIVE: To evaluate the use of transvaginal ultrasonography for diagnosing
      invasion of the bladder by cervical cancer. METHODS: Twenty-one women with stages
      Ib-IIIb cervical cancer underwent radical hysterectomy or staging laparotomy. All
      had computed tomography (CT) scans and cystoscopic examinations, and five also
      underwent magnetic resonance imaging (MRI). During transvaginal ultrasonography,
      a transvaginal transducer was inserted into the anterior fornix of the vagina and
      the bladder wall was studied in the sagittal plane. The moveability of the
      bladder wall was assessed by the ability of the bladder to slide along the
      uterine cervix when the probe was pushed up against the bladder from the anterior
      fornix. Moveability was considered to indicate an intact bladder wall. RESULTS:
      The accuracy of transvaginal ultrasonography was superior to that of the other
      methods for detecting bladder-wall invasion by cervical cancer. The accuracy was
      95% for transvaginal ultrasonography, 76% for CT, 86% for cystoscopy, and 80% for
      MRI. CONCLUSION: Transvaginal ultrasonographic examination is useful for
      detecting invasion of the bladder wall by cervical cancer.

PMID- 8290184
TI  - Successful heterotransplantation of human endometrium in SCID mice.
AB  - OBJECTIVE: To establish an experimental system useful for long-term evaluation of
      human endometrial tissue by its heterotransplantation to SCID mice. METHODS:
      Human endometrium was transplanted subcutaneously into SCID mice, nude mice, or
      nude mice given anti-asialo GM1 antibody, a natural killer activity suppressor.
      The transplant was observed by ultrasonography for up to 10 weeks and then
      morphologically. To assess the drug susceptibility of the transplant, danazol (10
      100 mg/kg/day orally), buserelin (0.01 mg/kg/day subcutaneously), or estradiol
      (0.5 mg/kg/day intraperitoneally) was administered to the host mice for up to 10
      weeks after the transplantation. Multiple-comparison procedures were used for
      statistical evaluation. RESULTS: The heterotransplant was accepted 100% in SCID
      mice and natural killer activity-suppressed nude mice, but was significantly
      inferior (40%) in nude mice at 10 weeks after the transplantation. The transplant
      size was volumetrically measurable noninvasively by ultrasonography. Using this
      SCID mouse model, we could evaluate drug effects on the transplanted endometrium.
      CONCLUSION: This system in SCID mice may be useful for evaluating drug actions on
      human endometrium and endometriotic tissues.

PMID- 8290185
TI  - Incremental increases in oxytocin infusion regimens for induction of labor at
      term in primigravidas: a randomized controlled trial.
AB  - OBJECTIVE: To compare induction of labor by intravenous oxytocin in regimens
      increasing incrementally at 15- and 30-minute intervals. METHODS: In a randomized
      controlled trial, 124 primigravidas requiring induction of labor by oxytocin
      infusion were randomly allocated to incremental increases at 30-minute intervals
      (62 patients) or 15-minute intervals (62 patients). The main outcomes assessed
      were mode of delivery, complications of labor and delivery (precipitate labor,
      hyperstimulation, postpartum hemorrhage, perineal tears, puerperal pyrexia), and
      number of days in the hospital. RESULTS: The 30-minute incremental regimen
      resulted in less precipitate labor (odds ratio 0.233, 95% confidence interval
      [CI] 0.042-0.55, chi 2 = 4.133), less uterine hyperstimulation (odds ratio 0.17,
      95% CI 0.015-1.906), and reduced length of stay in the hospital (difference in
      medians 3 days, 95% CI for difference in medians 2-4 days). The induction
      delivery interval was longer with 30 minutes (median 8 hours) than with 15
      minutes (median 5 hours) (difference in medians 2 hours, 95% CI for difference in
      medians 0-3 hours). With the 30-minute interval, there was a reduction in the
      occurrence of postpartum hemorrhage, perineal tears, and puerperal pyrexia, but
      these differences did not reach statistical significance. CONCLUSION: For the
      induction of labor in primigravidas, 30-minute incremental increases in the
      infusion rate of oxytocin were superior to a 15-minute incremental protocol in
      reducing the incidence of hyperstimulation and precipitous labor.

PMID- 8290186
TI  - High-dose oxytocin: 20- versus 40-minute dosage interval.
AB  - OBJECTIVE: To determine whether an increase in the oxytocin dosing interval would
      decrease the incidence of uterine hyperstimulation. METHODS: This study included
      1801 consecutive pregnancies receiving high-dose oxytocin. Oxytocin was used for
      labor augmentation in 1167 and induction in 634 women. Twenty- and 40-minute
      dosage intervals were compared. The study period was based on an 80% likelihood
      of detecting 5 and 10% differences in the cesarean and hyperstimulation rates,
      respectively. Statistics were analyzed with chi 2, Fisher, and Wilcoxon rank-sum
      tests where appropriate. Multivariate logistic regression and analysis of
      covariance were used to control for confounding demographic variables. RESULTS:
      Comparison of the 20- and 40-minute regimens for labor induction yielded no
      differences in the rates of cesarean delivery for dystocia (16 versus 19%) or
      fetal distress (5 versus 6%). The 20-minute regimen for augmentation was
      associated with a significant reduction in cesarean for dystocia (8 versus 12%; P
      = .05). The incidence of uterine hyperstimulation was greater with the 20-minute
      than the 40-minute regimen for induction (40 versus 31%; P = .02), but not for
      augmentation (31 versus 28%). Neonatal outcomes were unaffected by the dosage
      interval for both augmentation and induction. CONCLUSION: A 40-minute dosing
      interval for high-dose oxytocin offers no clear advantage over a 20-minute
      interval. Both regimens were safe and efficient, with no differences in perinatal
      outcome. The 20-minute interval was associated with fewer cesareans for dystocia
      when used for labor augmentation, whereas the 40-minute interval resulted in less
      hyperstimulation when used for labor induction.

PMID- 8290187
TI  - Pathophysiology of hypocalciuria in preeclampsia: measurement of intestinal
      calcium absorption.
AB  - OBJECTIVE: To analyze calcium absorption using stable isotopes in patients with
      preeclampsia and in normotensive controls. METHODS: Fifteen pregnant subjects
      were studied: eight with preeclampsia (hypertension and proteinuria) and seven
      normotensive controls. All patients were ingesting their normal diet. The
      subjects received two stable calcium isotopic tracers. An oral tracer (44Ca,
      0.0124 mmol/kg) was given with milk, while an intravenous tracer (42Ca, 0.00249
      mmol/kg) was infused over 7-10 minutes. Calcium concentration was determined by
      atomic absorption spectrophotometry, and isotope ratios by thermal ionization
      mass spectrometry from pooled 24-hour urine samples. RESULTS: No difference was
      noted in fractional intestinal absorption between preeclamptic subjects (0.282 +/
      0.051) and normotensive controls (0.306 +/- 0.079) (P = .49). However, the
      fraction of dietary calcium appearing in the urine differed significantly (0.06
      for preeclamptic subjects and 0.087 for normotensive controls; P = .008).
      CONCLUSIONS: Despite the indirect evidence of others, calcium absorption does not
      appear to be impaired in patients with preeclampsia. The retention site of the
      unexcreted calcium is unidentified.

PMID- 8290188
TI  - Intravaginal misoprostol versus dinoprostone as cervical ripening and labor
      inducing agents.
AB  - OBJECTIVE: To compare dinoprostone (prostaglandin E2) and misoprostol
      (prostaglandin E1) for ripening the cervix and inducing labor at term. METHODS:
      Sixty-three women were randomized to receive 100 micrograms misoprostol or 3 mg
      dinoprostone, both as intravaginal tablets. RESULTS: There was no statistical
      difference between the groups for pre-induction status. The mean Bishop scores
      before drug insertion were almost identical. Twelve hours after insertion, the
      mean change in the Bishop score was significantly higher in those receiving
      misoprostol (5.0 versus 3.3) (P = .008). However, there were no significant
      differences in induction-to-delivery interval, spontaneous labor rates, type of
      delivery, fetal outcome, or maternal complications. CONCLUSION: Misoprostol is as
      effective as dinoprostone for inducing labor at term.

PMID- 8290189
TI  - A new method using vaginal ultrasound and transfundal pressure to evaluate the
      asymptomatic incompetent cervix.
AB  - OBJECTIVE: To evaluate the ability of ultrasound with transfundal pressure to
      detect the incompetent cervix in pregnant women at risk for this condition.
      METHODS: One hundred fifty pregnant women with no prior pregnancy losses were
      scanned transabdominally, and 31 asymptomatic pregnant women with a prior history
      of cervical incompetency or risk for this condition were scanned transvaginally.
      The control patients were scanned once between 16-24 weeks, and the patients at
      risk were studied 73 times between 8-25 weeks. After evaluating the cervix and
      its internal os, transfundal pressure was applied. Cervical cerclages were placed
      for cervical funneling and shortening in response to transfundal pressure or for
      a grossly incompetent cervix on ultrasound evaluation. RESULTS: Transfundal
      pressure elicited no changes in the internal cervical os of the 150 control
      patients, of whom 141 delivered at term, two miscarried at 22 and 23 weeks, and
      seven delivered prematurely (4.7%). Fourteen of the 31 pregnancies at risk for
      cervical incompetency revealed opening of the internal os or descent of the fetal
      membranes with transfundal pressure. Thirteen of these 14 pregnancies were
      treated with cerclage, with nine (64%) proceeding to term, three (21%) delivering
      prematurely, and two (14%) aborting. The one patient who did not receive a
      cerclage also aborted. In six cases, the cervix and its internal os appeared
      normal but the membranes protruded into the endocervical canal in response to
      transfundal pressure. CONCLUSION: Application of transfundal pressure during
      transvaginal ultrasound evaluation of the cervix and its internal os may assist
      in detecting the asymptomatic incompetent cervix.

PMID- 8290190
TI  - Insulin requirements during pregnancy in women with type I diabetes.
AB  - OBJECTIVES: To document individual variations in the rise in insulin requirements
      during type I diabetic pregnancies, to relate the degree of increase to maternal
      characteristics and fetal outcome, and to examine these factors in a subgroup of
      patients experiencing a large fall in insulin requirement in the third trimester.
      METHODS: Insulin dose was documented in 237 pregnancies in women with type I
      diabetes. Multiple regression analysis was performed to identify significant
      associations with maternal and fetal characteristics. Eighteen pregnancies with a
      fall in insulin requirement of 30% or more in the third trimester were considered
      in detail. RESULTS: The mean absolute increase in insulin requirement was 52
      units. The degree of rise was significantly related to maternal weight gain
      between 20-29 weeks and maternal weight at booking, and was inversely related to
      duration of diabetes. It was not related to the degree of diabetes control,
      complications of pregnancy, White class, or outcome of pregnancy. In the 18 women
      experiencing a large fall in insulin requirement, there was no relation with
      maternal characteristics or fetal outcome. CONCLUSION: There is a wide individual
      variation in the change in insulin requirements in type I diabetic pregnancy. The
      degree of increase is related only to maternal weight gain during weeks 20-29 and
      maternal weight at booking, and is inversely related to duration of diabetes.
      Large falls in insulin requirement remain unexplained and may not be associated
      with placental failure.

PMID- 8290191
TI  - High-velocity penetrating wounds of the gravid uterus: review of 16 years of
      civil war.
AB  - OBJECTIVE: To evaluate the value of selective laparotomy in pregnant women with
      penetrating abdominal injuries. METHODS: A retrospective survey was carried out
      at our center over 16 years of civil war, extending from 1975 to 1991. Fourteen
      pregnant women had uterine injuries secondary to high-velocity abdominal
      penetrating trauma. The corresponding management was evaluated carefully with
      respect to maternal and fetal outcomes. RESULTS: Two maternal deaths occurred,
      neither resulting solely from intra-abdominal injuries. Visceral injuries were
      present when the entrance of the missile was in either the upper abdomen or the
      back. When the entry site was anterior and below the uterine fundus, visceral
      injuries were absent in all six women upon surgical exploration. Perinatal deaths
      occurred in half of the cases and were due to maternal shock or uteroplacental or
      direct fetal injury. Immediate cesarean delivery was performed because of either
      limited surgical field exposure, fetal injury, or distress. Three patients
      explored were managed by delaying delivery. All later delivered vaginally with
      successful fetal outcomes in all three. CONCLUSION: Selective laparotomy may be
      considered in pregnant women with anterior penetrating abdominal trauma, as the
      likelihood of intra-abdominal injuries may be predicted based on the location of
      the penetrating wound.

PMID- 8290192
TI  - Effects of chronic exercise on blood volume expansion and hematologic indices
      during pregnancy.
AB  - OBJECTIVE: To compare blood volumes and hematologic indices between nine
      aerobically trained, physically active pregnant women who continued to exercise
      throughout gestation and five healthy yet sedentary gravidas. METHODS: Subjects
      were tested on three occasions: 25 and 36 weeks of pregnancy and 12 weeks
      postpartum. Plasma volumes were estimated by dye dilution with Evans blue. Blood
      samples were taken from the antecubital vein with the subjects resting in a
      seated, semirecumbent position. In addition to plasma volume estimations, blood
      samples were analyzed for hematocrit ratio, hemoglobin concentration, red cell
      count, and plasma protein concentration. Blood volumes and red cell volumes were
      calculated from plasma volume estimates and hematocrit ratios. RESULTS: Average
      birth weight and length of gestation did not differ between the subject groups.
      Analysis of variance indicated that absolute blood volume measures were
      significantly greater (P < .01) in the physically active compared to sedentary
      subjects at all three test times. Similar results were found for plasma and red
      cell volumes (P < .01). Blood volumes relative to body weight were significantly
      higher in physically active subjects (P < .01) than in their sedentary
      counterparts at 25 weeks (88.5 versus 75.5 mL/kg) and at 36 weeks (88.4 versus
      70.9 mL/kg), as well as at 12 weeks postpartum (72.2 versus 57.6 mL/kg). All
      vascular volumes were significantly (P < .001) lower at 12 weeks postpartum
      compared to those seen during pregnancy in both subject groups. Hematologic
      indices of hematocrit ratio, hemoglobin concentration, red cell count, and plasma
      protein concentration were all greater (P < .001) at 12 weeks postpartum than
      during pregnancy. CONCLUSIONS: Physically active women possessed significantly
      greater vascular volumes than their sedentary counterparts. Although this
      difference was maintained throughout gestation as the active gravidas continued
      to exercise, there was no apparent effect on pregnancy outcome.

PMID- 8290193
TI  - Postoperative effects of fentanyl, ketorolac, and piroxicam as analgesics for
      outpatient laparoscopic procedures.
AB  - OBJECTIVE: To compare postoperative analgesia and side effects of intramuscular
      ketorolac, intravenous fentanyl, and oral piroxicam on healthy women undergoing
      laparoscopic surgery. METHODS: The study was a randomized double-blind clinical
      trial of three analgesic drugs. An initial 100-micrograms dose of fentanyl was
      given at induction, with 25-micrograms boluses after 45 and 90 minutes of
      operating time. Piroxicam, 40 mg, and ketorolac, 60 mg, were administered 90 and
      30 minutes before induction, respectively. RESULTS: Eighty-four subjects were
      included in the analysis. Ketorolac patients (N = 29) spent significantly less
      time in the recovery room (median 96 minutes) than those receiving fentanyl (N =
      27) (median 121 minutes; P < .01) or piroxicam (N = 28) (median 124 minutes; P <
      .01) or a verbal descriptive scale, more fentanyl patients (38%) experienced
      moderate pain at discharge than ketorolac (11%; P < .05) or piroxicam (4%; P <
      .01) patients. The incidence of measured side effects did not differ
      significantly between groups. CONCLUSIONS: Intramuscular ketorolac was associated
      with shorter recovery room stays while providing analgesia equal to intravenous
      fentanyl or the oral nonsteroidal antiinflammatory drug piroxicam.

PMID- 8290194
TI  - Repeated clinic laparoscopy for the treatment of pelvic adhesions: a pilot study.
AB  - OBJECTIVE: To evaluate the safety and feasibility of repeat outpatient
      laparoscopy following laparoscopic lysis of extensive pelvic adhesive disease in
      a standard operating room setting. METHODS: In a pilot study, eight patients with
      chronic pelvic pain associated with severe pelvic and abdominal adhesive disease
      underwent standard operative laparoscopic adhesiolysis. Tenckhoff catheters were
      placed in the abdominal wall during the procedure to allow repeat laparoscopy in
      an outpatient clinic setting with a 2-mm laparoscope. Successful adhesiolysis was
      documented in follow-up laparoscopy with the Optical Catheter System, performed 3
      months later in four patients. RESULTS: Laparoscopy via the Tenckhoff catheters
      was accomplished in 26 of 32 attempts (81.3%). One patient had re-forming
      adhesions lysed with the Optical Catheter System. Simultaneous vaginal ultrasound
      enhanced visualization of the cul-de-sac. CONCLUSIONS: Outpatient clinic
      laparoscopy with a 2-mm laparoscope may prove practical for general diagnostic
      purposes. If validated in controlled trials with larger populations, the
      procedure may be an effective treatment of pelvic adhesive disease.

PMID- 8290196
TI  - Transforming growth factor-beta activity is increased in peritoneal fluid from
      women with endometriosis.
AB  - OBJECTIVE: To investigate the presence of transforming growth factor-beta in
      peritoneal fluid of women with and without endometriosis. METHODS: Fifty-two
      peritoneal fluid samples, obtained during laparoscopies performed for tubal
      ligation (n = 10), infertility (n = 38), or pain (n = 4), were examined for the
      presence of transforming growth factor-beta using the Mv1Lu cell growth
      inhibition assay. At laparoscopy, 26 women had endometriosis. The other 26 women
      had no endometriosis; 16 of them had infertility, and ten who had no pelvic
      pathology at tubal sterilization served as fertile controls. RESULTS: The
      concentration of transforming growth factor-beta was increased in the peritoneal
      fluid from women with endometriosis (11.4 +/- 3.3 ng/mL) compared to both the
      fertile control group without endometriosis (1.1 +/- 0.29 ng/mL) and the
      infertile control group without endometriosis (3.6 +/- 1.4 ng/mL). Twenty-five of
      the 52 women (48%) demonstrated levels of transforming growth factor-beta higher
      than 2 ng/mL. Patients with endometriosis were significantly more likely to have
      elevated concentrations of transforming growth factor-beta than were women
      without endometriosis (16 of 26, 61.5%, versus nine of 26, 34.6%). CONCLUSIONS:
      These findings demonstrate the presence of transforming growth factor-beta in
      peritoneal fluid. Elevated levels in women with endometriosis could be important
      in the pathophysiology of this disease.

PMID- 8290195
TI  - Piperacillin and tazobactam versus clindamycin and gentamicin in the treatment of
      hospitalized women with pelvic infection. The Piperacillin/tazobactam Study
      Group.
AB  - OBJECTIVE: To compare the efficacy and safety of a combination of piperacillin
      and tazobactam with that of clindamycin and gentamicin in the treatment of
      hospitalized women with infections of the upper genital tract. METHODS: This was
      a randomized open-label trial in hospitalized women with infections of the upper
      genital tract. Patients were recruited at 12 hospitals in the United States and
      two hospitals in Canada and were randomly assigned to one of two regimens in a
      2:1 ratio. One group received piperacillin, 3 g every 6 hours, and tazobactam,
      375 mg every 6 hours; the other group received clindamycin, 900 mg every 8 hours,
      and gentamicin, 2.5-5.0 mg/kg/day in three divided doses. Therapy with the
      assigned regimen was to be administered for a minimum of 3 days. Cultures for
      aerobic and anaerobic bacteria were obtained from the site of infection before
      initiation of therapy. Cultures for Chlamydia trachomatis were also obtained from
      patients with endometritis or pelvic inflammatory disease. Subjects were
      evaluated for clinical and bacteriologic response at 24-72 hours and 2-4 weeks
      after completing therapy. RESULTS: Two hundred ninety-nine patients were
      enrolled; 196 were in the piperacillin-tazobactam group and 103 were in the
      clindamycin-gentamicin group. The most common diagnoses were endometritis (146)
      and pelvic inflammatory disease (115). The most common microorganisms recovered
      included: Peptostreptococcus sp (99), Prevotella sp (87), black pigmented
      Bacteroides (29), B fragilis (11), enterococci (64), group B streptococcus (26),
      Escherichia coli (31), Neisseria gonorrhoeae (49), and C trachomatis (19). A
      favorable clinical response occurred in 84.7% (166 of 196) of piperacillin
      tazobactam patients and 87.3% (90 of 103) of clindamycin-gentamicin patients.
      Among those evaluable for bacteriologic response, 78% (67 of 86) and 82% (23 of
      28), respectively, had a favorable response. Diarrhea occurred significantly more
      frequently in the piperacillin-tazobactam group (9.7 versus 2.9%; P = .04), but
      the majority of episodes were mild to moderate. None of the adverse experiences
      in either treatment group were considered life-threatening and drug-related.
      CONCLUSION: The combination of piperacillin and tazobactam is an effective and
      well-tolerated antibiotic regimen for the treatment of infections of the upper
      genital tract in women.

PMID- 8290197
TI  - Ovarian malposition in women with uterine anomalies.
AB  - OBJECTIVE: To evaluate the incidence of malposition of the ovary in patients with
      uterine anomalies compared to patients with a normal uterus. METHODS: Ovarian
      malposition was investigated in 1082 patients via laparoscopy. Only ovaries in
      which the upper pole was attached to the area above the common iliac vessels were
      designated as malpositioned; often the lower pole was attached inside the pelvis.
      These patients were divided into two groups. Group I consisted of women with
      congenital uterine anomalies (divided into subgroup A, congenital absence of the
      uterus and unicornuate uterus, and subgroup B, other uterine anomalies). Group II
      included those women with a normal uterus (control group). RESULTS: The incidence
      of malposition of the ovary was higher in group I than group II (P < .001). When
      we separately compared subgroup A and subgroup B with the control group, only
      subgroup A had a significantly higher incidence (P < .001). CONCLUSION: Our
      results reveal that the incidence of malposition of the ovary is higher in
      patients with congenital uterine anomalies than in a control group. This is
      especially true when the uterus is absent or is only partially present.

PMID- 8290198
TI  - Hysteroscopic endomyometrial resection: a new technique for the treatment of
      menorrhagia.
AB  - Thirty-five patients with menorrhagia and a normal uterine cavity underwent
      hysteroscopic endomyometrial resection. None underwent any form of medical or
      surgical preparation of the endometrium. A standard gynecologic resectoscope was
      used to excise a minimum of 3 mm of endomyometrium from the entire uterine
      cavity. This depth was reduced to 2 mm at the tubal ostia. All patients were
      followed for 3-6 months. Twenty-one of the 25 patients (84%) who were followed at
      6 months reported amenorrhea. The mean dysmenorrhea scores improved from 2.84 to
      0.56 postoperatively. Seven of the 35 patients were diagnosed with adenomyosis.
      One woman was found to have adenomatous hyperplasia of the endometrium.
      Hysteroscopic endomyometrial resection is a highly effective method for the
      treatment of menorrhagia. This technique produces a very high rate of amenorrhea,
      provides a histologic specimen of the endomyometrium, and obviates the need for
      medical or surgical preparation of the endometrium.

PMID- 8290199
TI  - An improved ligator in operative laparoscopy.
AB  - The Clarke ligator scissor forceps simplifies the tying of square knots, such as
      the surgeon's knot. This ligator also facilitates square-knot loop ligation and
      functions as a forceps and suture cutter.

PMID- 8290200
TI  - Fetal heart rate recorder for long-duration use in active full-term pregnant
      women.
AB  - We sought to assess the signal consistency and accuracy of a long-duration fetal
      heart rate (FHR) recorder (a 1-MHz ultrasonic Doppler transducer composed of six
      miniprobes and an autocorrelation technique) in active, full-term pregnant women.
      The FHR data of 15 normal full-term fetuses were obtained every 250 milliseconds
      in various maternal positions using the new Doppler system or a direct scalp
      electrocardiographic (ECG) transducer. Differences between simultaneous Doppler
      and ECG measures were small and within acceptable limits except for short-term
      variability. Signal loss, assessed in 15 subjects in various positions, was less
      than 10% except during sitting or walking. The mean (+/- standard deviation)
      percentages of FHR signals lost over 2 hours in bed, 1 hour out of bed, and 24
      hours in and out of bed were 1.2 +/- 2.1, 12.9 +/- 16.2, and 3.8 +/- 4.4,
      respectively. This system for recording FHR is suitable for clinical research and
      routine FHR monitoring, and provides data comparable to Holter ECG monitoring in
      patients with heart disease.

PMID- 8290201
TI  - Evacuation proctography (defecography): an aid to the investigation of pelvic
      floor disorders.
AB  - Patients with pelvic floor disorders frequently have associated anorectal
      dysfunction, which can be evaluated by a variety of laboratory tests. Evacuation
      proctography (defecography) documents the process of rectal evacuation and
      therefore demonstrates disorders of defecation, particularly those of an
      obstructive nature. It provides objective information about rectocele size and
      emptying and demonstrates coexistent enteroceles, many of which are missed on
      physical examination. This radiographic technique is the method of choice for
      recognizing rectal intussusception, the mechanism by which rectal prolapse
      occurs. Proctography suggests the diagnosis of spastic pelvic floor (anismus), a
      disorder amenable to biofeedback therapy. Proctography has limited application in
      anal incontinence unless there are associated obstructive symptoms. Evaluation of
      bladder dysfunction is aided by concomitant cystography. Gynecologists managing
      pelvic floor disorders should assess coexistent anorectal dysfunction, as
      undiagnosed enteroceles and disorders of defecation are an important cause of
      persistent or recurrent symptoms following pelvic floor repair. A comprehensive
      interdisciplinary approach to pelvic floor disorders is recommended.

PMID- 8290203
TI  - Tuberculosis speeds enforcement memo.

PMID- 8290202
TI  - The status of ethics education in obstetrics and gynecology.
AB  - To establish the present status of ethics education in obstetrics and gynecology,
      256 questionnaires were sent to residency (graduate) and student (undergraduate)
      education programs. One hundred ninety-eight questionnaires were returned.
      Fifteen programs offered no ethics education; 167 offered resident level courses;
      123 offered undergraduate (student) level courses; and 84 offered postgraduate
      education. The median number of hours offered was 2 undergraduate, 4 graduate,
      and 2 postgraduate. The courses offered relied primarily on formal lecture
      presentation, even though this was not considered most effective by the
      respondents. Most institutions (85%) used more than one format to present ethics
      material. General ethics principles were covered in 78% of the reporting
      institutions. Where ethics case histories were used, they were rated higher in
      efficacy by the respondents. Only 15% of the reporting institutions had any means
      of measuring outcomes. The issues cited most frequently as critical in a
      curriculum were abortion, maternal-fetal conflicts, issues surrounding care
      decisions at the end of life, and informed consent. The few hours dedicated to
      ethics were small relative to a long list of issues. Obstetric-gynecologic
      faculty with any training in medical ethics were uncommon (29%). The form of
      teaching, except in rare circumstances, seemed to lack structure or design and
      used few of the available reading materials. Recommendations from this survey
      include the development of a uniform national curriculum for undergraduate and
      graduate medical ethics, development of evaluation alternatives for ethics
      education, and encouragement and support for faculty development in medical
      ethics.

PMID- 8290204
TI  - Injury surveillance system may expand.

PMID- 8290205
TI  - Organochlorine-cancer link eyed for phaseout.

PMID- 8290206
TI  - Customized prevention programs play vital role in back protection process.

PMID- 8290207
TI  - Proper medical management can reduce cumulative trauma disorder incidence.

PMID- 8290208
TI  - 106 years later.

PMID- 8290209
TI  - Glaucoma drainage implants in pediatric patients.
AB  - To assess the use of drainage implants in pediatric patients with glaucoma
      refractory to conventional medical and surgical therapy, we retrospectively
      reviewed 20 consecutive eyes in children 10 years of age or younger treated with
      16 Molteno (three of which were removed and replaced with second Molteno shunts)
      and seven Baerveldt implants. The age of the patients ranged from 1 month to 10
      years (mean, 3 years). The patients had undergone a mean of two previous failed
      glaucoma procedures (range, one to six). The mean intraocular pressure (IOP)
      prior to drainage tube implantation was 37 +/- 4 mm Hg, compared with a mean of
      18 +/- 6 mm Hg following surgery, with average postoperative follow up of 25
      months (range, 8 to 41 months). The overall success, defined as IOP < or = 21 mm
      Hg without further surgical therapy, was 80%. Postoperative glaucoma medications
      were required in 75% of patients. There were 23 complications, one of which
      resulted in decreased visual acuity. These findings demonstrate that drainage
      tube implants can be effective in lowering IOP in uncontrolled pediatric
      glaucomas. Patients often require postoperative glaucoma medications and close
      monitoring for complications.

PMID- 8290210
TI  - Prediction of postoperative visual acuity in patients with total glaucomatous
      cupping using the Potential Acuity Meter and automated perimetry.
AB  - We evaluated the effectiveness of using the Potential Acuity Meter (PAM) and
      automated perimetry to predict postoperative vision in 30 advanced glaucoma
      patients following combined cataract extraction and trabeculectomy. Using the
      binomial distribution at alpha = 0.05, PAM and automated perimetry individually
      were significantly useful in predicting postoperative vision of 20/40 or better.
      Automated perimetry, but not PAM, was useful in predicting worse than 20/40
      vision. Used together, automated perimetry and PAM testing were significantly
      useful in predicting vision worse or better than 20/40.

PMID- 8290211
TI  - Trabeculotomy ab externo: an alternative treatment in adult patients with primary
      open-angle glaucoma.
AB  - Seventy-nine adult patients with primary open-angle glaucoma (POAG) were randomly
      assigned to treatment by modified trabeculotomy ab externo (TAB) (n = 44) and by
      trabeculectomy with adjunctive mitomycin C (TMC) (n = 35), and the postoperative
      outcomes achieved with these two techniques were compared. With TAB, the
      probability of successful intraocular pressure control 1 year postoperatively was
      .8644; with TMC, .8432; the difference is not significant (P = .7956). However,
      postoperative complications such as corneal epithelial damage, bleb leaks,
      hypotony, flat anterior chamber, and serous choroidal detachment were
      significantly less frequent in the TAB group. Largely because of this latter
      consideration, in selected cases, TAB may be a viable alternative to TMC.

PMID- 8290212
TI  - Histopathology of argon laser peripheral iridoplasty.
AB  - We report the light and electron microscopic findings from two eyes treated with
      argon laser peripheral iridoplasty (ALPI) for bilateral angle-closure glaucoma.
      The patient, a 45-year-old man, died from complications of acquired
      immunodeficiency syndrome 16 days following ALPI. Ocular pathologic findings
      included contraction furrow formation and proliferation of fibroblast-like cells,
      accompanied by collagen deposition on the iris surface, denaturation of stromal
      collagen, and coagulative necrosis of blood vessels within the anterior two
      thirds of the iris stroma. These findings suggest that heat shrinkage of collagen
      may be responsible for the short-term response to ALPI, and that contraction of
      the fibroblastic membrane may be responsible for its long-term effects.
      Additionally, the presence of coagulative necrosis of iris blood vessels suggests
      that overt treatment may result in iris necrosis. To our knowledge this is the
      first report of the histopathology of ALPI.

PMID- 8290213
TI  - Effects of cycloplegia and iris pigmentation on postoperative intraocular
      inflammation.
AB  - Using the Kowa laser flare cell meter, we investigated the relation between
      anterior chamber inflammation following phacoemulsification and posterior chamber
      intraocular lens implantation, and (1) iris color and (2) the use of 1%
      cyclopentolate hydrochloride for 1 week postoperatively. One hundred sixty eyes,
      randomized into either a cycloplegic or noncycloplegic group, and classified into
      four different iris color groups--blue, brown, green, and hazel--were studied.
      Eyes with brown irides had significantly more intense flare 2 weeks
      postoperatively than eyes with blue irides. Overall, postoperative flare tended
      to be related to the degree of iris pigmentation. Use of 1% cyclopentolate
      hydrochloride for 1 week postoperatively failed to decrease anterior chamber
      inflammation in any of the eyes.

PMID- 8290214
TI  - Canaliculorhinostomy following dacryocystectomy for removal of a benign fibrous
      histiocytoma of the lacrimal sac.
AB  - A 41-year-old woman had epiphora and a right lacrimal sac mass. A solid mass
      filling the entire lacrimal sac was found at surgery. After a month of testing
      and evaluation at the Armed Forces Institute of Pathology, the final diagnosis
      was benign fibrous histiocytoma. A dacryocystectomy was performed, and the entire
      tumor was removed. The area of the common canaliculus was then attached to a
      nasal mucosal flap, and the system was intubated with silicone tubing for 1 year.
      Two years after the tubing was removed, the epiphora had resolved and there was
      no recurrence of the tumor.

PMID- 8290215
TI  - The necessity of long-term follow up after surgery for basal cell carcinomas of
      the eyelid.
AB  - Both diagnostic and therapeutic problems remain in the treatment of basal cell
      carcinomas of the eyelid. Incorrect initial diagnosis and resulting inadequate
      treatment can lead to the loss of the bulbus. Inadequate follow up may result in
      failure to detect a recurrent tumor. We retrospectively studied 226 patients with
      basal cell carcinoma of the eyelid who had surgery some time between 1980 and
      1989. In 179 patients, a primary lid tumor was removed; the recurrence rate for
      these patients was 6.1%. Forty-seven patients had surgery for secondary eyelid
      basaliomas; the recurrence rate for these patients was 14.8%. These recurrence
      rates correlated clearly with the horizontal extent and depth of the tumor, and
      with the appearance of the sclerodermiform type. The fact that recurrences were
      found after 3 years demonstrates the importance of long-term follow up in these
      patients, especially in those with secondary tumors and tumors of exceptional
      height.

PMID- 8290216
TI  - Perfluoroperhydrophenanthrene (Vitreon) in the management of giant retinal tears:
      results of a collaborative study.
AB  - Fifty cases of retinal detachment with a giant retinal tear were managed using
      perfluoroperhydrophenanthrene (Vitreon) as an intraoperative and postoperative
      tool. The giant tear was less than 180 degrees in 76% of the eyes, greater than
      180 degrees in 22%, and greater than 270 degrees in 2%. Proliferative
      vitreoretinopathy was present in 40%. Vitreon was used only intraoperatively in
      84% of the eyes, and was left in 16% for up to 4 weeks. Intraoperative retinal
      reattachment was achieved in 98%. Retinal attachment was maintained in 88%, with
      a mean follow up of 8.6 months. Postoperative visual acuity was better than
      20/400 in 52%. Postoperative complications included cataract in 23%, choroidal
      effusion in 2%, hypotony in 4%, and recurrent retinal detachment with
      proliferative vitreoretinopathy in 26%.

PMID- 8290217
TI  - Merkel cell carcinoma of the eyelid.
AB  - The Merkel cell is part of the dendritic cell population of the epidermis, and
      studies suggest it has a role as a slowly adapting mechanoreceptor involved with
      mediating the sense of touch. Merkel cells can give rise to malignant neoplasms,
      one tenth of which occur in the eyelid and periocular area, and manifest as
      painless erythematous nodules, with overlying telangiectatic blood vessels.
      Merkel cell carcinoma can mimic other malignant lesions, and the diagnosis can be
      difficult. One third of the tumors recur, and there is a high rate of metastasis.
      The estimated 5-year survival rate is 38%. Initial treatment should be
      aggressive, including surgical resection, with consideration of postoperative
      radiation. Merkel cell carcinoma responds to chemotherapy, but routinely recurs
      on cessation of treatment. Two cases are presented to illustrate the typical
      presentation of Merkel cell carcinoma and the importance of electron microscopy
      and immunohistochemical studies.

PMID- 8290218
TI  - Subconjunctival dislocation of posterior chamber intraocular lens.
AB  - A posterior chamber intraocular lens (PC-IOL) dislocated into the subconjunctival
      space following a concussion injury in a 24-year-old man who had gained good
      visual acuity following extracapsular cataract extraction and PC-IOL implantation
      for a steroid-induced cataract. Except for long-term use of topical steroid
      therapy for vernal catarrh, the patient had no systemic or ocular predisposing
      factors for wound dehiscence. Given the risk of endophthalmitis, the PC-IOL was
      removed and anterior vitrectomy was performed on an emergency basis. To our
      knowledge, this is the second documented case of a subconjunctivally dislocated
      PC-IOL.

PMID- 8290219
TI  - THC:YAG nasolacrimal duct recanalization.
AB  - In an early exploration of a new technique for creating a patent nasolacrimal
      duct system, a chromium-sensitized and thulium- and holmium-doped YAG laser was
      used to canalize the nasolacrimal duct of a fresh-frozen bisected human cadaver
      head. The laser--long-pulsed (300 milliseconds), compact, self-contained, and
      solid-state--operates in the near infrared range (2.1 microns). The technique
      involved passing a 550-micrometer quartz fiberoptic through the dilated superior
      punctum and canalicular system, down through the nasolacrimal duct. The quartz
      fiberoptic was then withdrawn into the area of the lacrimal sac. Pulse energies
      of 500 mJ were used at a repetition rate of five pulses per second to ablate the
      duct lining. The nasolacrimal duct was then unroofed and the epithelial lining of
      the duct histopathologically evaluated.

PMID- 8290220
TI  - A temporary dissecting seton for trabeculectomy: delayed re-creation of the
      glaucoma filtering sclerostomy and bleb.
AB  - Presented is a new surgical technique to re-create the entire filtering pathway 2
      weeks following trabeculectomy. The dissecting seton is a suture loop of 9-0
      nylon, silk, or polypropylene placed in the potential outflow space of the
      sclerostomy and bleb area during trabeculectomy. The seton is pulled out at the
      slit lamp, under topical anesthesia, 1 to 3 weeks after the initial surgery in
      order to re-create the filtration pathway. By pulling on the seton, a
      cheesewiring dissection severs newly formed fibrovascular tissue that may have
      occluded or constricted the previously created aqueous outflow tract at any
      point(s). Because of the significant time delay, the reopened filtration pathway
      is, for the first time, filled with flowing aqueous of nearly normal composition
      under a well-healed conjunctiva as a result of a nearly normally functioning
      ciliary body in a nearly quiet eye. Delayed postoperative re-creation of the bleb
      with the dissecting seton may be combined with other management techniques such
      as 5-fluorouracil subconjunctival injections, suture cuttings, bleb massage, etc.
      This technique has been used in nine cases with follow up ranging from a few
      weeks to 1 year. All were trabeculectomies with phacoemulsification and
      intraocular lens implantation. Both initial placement and subsequent handling of
      the dissecting seton appear to be safe, quick, easy, and inexpensive.
      Complications or failures have all been minor and easily managed.

PMID- 8290221
TI  - Nasal secretion and intraocular surgery.

PMID- 8290222
TI  - Management of acute and chronic lateral ligament injuries of the ankle.
AB  - Acute and chronic lateral ligament injuries of the ankle represent a common but
      persistent problem to orthopedic specialists. A comprehensive physical
      examination and classification system were proposed as an approach to this
      problem. Guidelines for both conservative and surgical management for acute and
      chronic injuries are described. A comparison of the most common lateral ligament
      repairs is provided, with emphasis on the benefits of the so-called anatomic
      repair.

PMID- 8290223
TI  - Posterior tibial tendon problems in athletes.
AB  - Posterior tibial tendon problems are uncommon sources of disability in athletes.
      Awareness of the condition and early diagnosis are important to prevent
      disability and prolonged time away from sports. Appropriate imaging studies will
      aid in diagnosis. Tendon tears in younger patients are different than the typical
      ruptures seen in middle-aged and older adults. Treatment must be individualized
      based on the type of tear and degree of deformity present. Other conditions such
      as dislocation of the posterior tibial tendon, accessory navicular and exertional
      compartment syndrome can involve the tibialis posterior muscle and present as
      diagnostic dilemmas.

PMID- 8290224
TI  - Peroneal tendon injuries.
AB  - Injuries to the peroneal tendons are common. Acute injuries of the peroneus
      brevis tendon include tendinitis; avulsion of the insertion with or without bone
      fragment, i.e., styloid fracture of the fifth metatarsal; lacerations; and acute
      dislocation with or without a "rim fracture." Chronic lesions include
      longitudinal rents in the tendon either alone or associated with other localized
      disease. Lesions of the peroneus longus tendon include rupture and longitudinally
      oriented chronic tears, perhaps with a fragmented os perineum. Treatment for
      these entities is discussed.

PMID- 8290225
TI  - Subcalcaneal heel pain.
AB  - Subcalcaneal heel pain is a very common presenting complaint. Careful evaluation
      is necessary to guide treatment decisions. By far, most subcalcaneal heel pain
      resolves with appropriate conservative treatment over a period of weeks to
      months. Occasionally, when surgery is necessary, the goal of the procedure is
      adequate decompression in the area of the origin of the plantar fascia and medial
      calcaneal tubercle.

PMID- 8290226
TI  - Arthroscopic treatment of ankle injuries.
AB  - Arthroscopic examination of the ankle joint permits complete examination of the
      intra-articular structures. With recent advances in equipment and additional
      experience, numerous ankle problems can be handled arthroscopically. These
      problems include treatment of soft-tissue and bony impingement, osteochondral
      lesions of the talus, removal of loose bodies, treatment of acute and chronic
      fractures, lateral ankle stabilization, and arthroscopic fusion procedures.

PMID- 8290227
TI  - Achilles tendinitis.
AB  - Achilles tendinitis is a common condition of overuse seen in active individuals.
      It is multifactorial, usually due to a combination of anatomic and biomechanical
      characteristics along with poor training technique. Pathologic changes can
      involve the surrounding tissue (bursae, paratenon) or the tendon itself and can
      occur both at its insertion into the calcaneous and the critical hypovascular
      zone. A clear understanding of the cause and stage of the condition is critical
      for successful treatment, be it conservative or surgical. Recent advances in
      surgical technique and postoperative rehabilitation have been promising in
      returning individuals to their previous levels of activity.

PMID- 8290228
TI  - Conditions of the toenails.
AB  - Athletes are susceptible to developing toenail problems because of the speed or
      intensity of play (runners), the starting and stopping nature of the sport
      (tennis, racquetball), and the type of activity and shoes they wear or do not
      wear (ballet dancers, gymnasts). They may also have other conditions, such as
      hallux valgus, claw toes, gout, diabetes, arthritis, or fungus infection of the
      nails, that may influence the decision on the type of treatment recommended. Nail
      trauma that could result in osteomyelitis; secondary effects of arthritis, such
      as the development of a mucous cyst; and the infected ingrown toenail are seen
      frequently in the athlete and can be satisfactorily treated by the orthopedist.

PMID- 8290229
TI  - Treatment of bunion deformity in the athlete.
AB  - Bunions occur in athletes. Often, the bunion is compensated and has a congruous
      joint, needing minimal treatment. If the bunion rapidly progresses, the sesamoids
      sublux, and the joint becomes incongruous; surgery becomes necessary. Surgery for
      decompensated bunions and secondary problems is discussed.

PMID- 8290230
TI  - Haglund's deformity and retrocalcaneal bursitis.
AB  - An excessive prominence of the bursal projection in the posterosuperior aspect of
      the calcaneous constitutes Haglund's deformity. Swelling in this area constitutes
      Haglund's disease and is associated with retrocalcaneal bursitis. Rigid and
      prominent heel counters with high heels impinge on the soft tissues overlying the
      prominence and give rise to symptoms of pain and swelling. Cavo varus deformities
      exacerbate this problem. The bursal projection can be demonstrated radiologically
      by a superior calcaneal angle of more than 75 degrees, a combination of calcaneal
      inclination and a posterior calcaneal angle of more than 90 degrees, and
      excessive bone above the upper parallel pitch line. Conservative treatment should
      always be implemented, and only those that have not benefited from such therapy
      should be considered for surgery. The results of surgery are satisfactory,
      provided adequate bone has been resected and no damage to local peripheral nerves
      or the Achilles tendon has been sustained. After a period of immobilization, an
      appropriate rehabilitation program must complement the treatment to ensure the
      early return of function to the tendons and surrounding joints.

PMID- 8290231
TI  - Nerve entrapment, neuropathy, and nerve dysfunction in athletes.
AB  - Nerve entrapment, neuropathy, and nerve dysfunction in the legs, ankles, and feet
      of athletes are not uncommon conditions. Frequently, the conditions are
      overlooked as the more obvious musculoskeletal injury draws the physician's
      attention. Typically, with conservative treatment, including an occasional
      injection of local anesthetic with and without corticosteroid, resolution is
      achieved. Rarely, symptoms are severe and diffuse enough to require
      administration of a tricyclic antidepressant medication to decrease the nerve
      irritability. In cases that fail to respond to conservative treatment and have
      well-localized neurologic findings, surgery may be indicated. During surgery, the
      nerve should be minimally manipulated. The surrounding veins, arteries, and fat
      should be relatively undisturbed. Critical to understanding and treating these
      problems is a thorough knowledge of the peripheral neuroanatomy.

PMID- 8290232
TI  - Treatment of Freiberg's disease.
AB  - Freiberg's disease is a relatively rare condition with a multifactorial cause in
      which trauma and circulation must play a major but not solitary role. Once the
      condition presents itself, early treatment is geared toward reducing its symptoms
      and preventing progression. If conservative measures fail, many surgical options
      are available. One of these, the dorsiflexion osteotomy of the metatarsal head is
      presented as a logical procedure that is simple, reliable, not destructive, and
      capable of good results regardless of the stage of the disease.

PMID- 8290234
TI  - ["Serrated" adenoma--a little known type of colorectal tumors].
AB  - Eight cases and review of the literature on serrated adenoma of the colon were
      reported. This distinct entity of colorectal tumors was described in recent
      years. The tumors contain hyperplastic and adenomatous areas. Their tendency for
      malignant transformation is similar to pure adenomas to contrary to benign
      hyperplastic polyps. Three tumors of eight reported cases were pedunculated,
      while five were sessile. Four patients were operated on because of narrowing of
      intestinal lumen by the tumors. Malignant transformation of tumors was observed
      in three cases. Several biopsies were performed before major operations.
      Histology showed false benign hyperplastic tumors. Importance of multiple tissue
      sample for histology was emphasised. Electron microscopy showed disturbed
      differentiation and pathological mucus production of tumor cells.

PMID- 8290233
TI  - [Sialidase activity in cervical connective tissue during cervix maturation and
      dilatation during labor].
AB  - The authors obtained small pieces of materials from portio vaginalis uteri of 122
      women being in postmenopause and premenopause, in different stages of pregnancy
      and parturition concerning directly after delivery. Different biochemical
      investigations of these 30-200 mgs specimens were performed to study the
      physiological background of its ripening process. They examined the changes in
      activity of sialidase which cleaves terminal sialic acids. The authors performed
      these investigations with the use of Triticum vulgaris (WGA) and Limulus
      polyphemus (LPA) agglutinins (lectins) marked with FITC. The evaluation of the
      lectin linkage happened with fluorescence microscope. They evaluated the whole
      fluorescence of extracellular matrix but separately of different extracellular
      matrix elements as well. From their investigations was stated that the number of
      WGA and LPA binding sites of the uterine cervix increases predominantly in the
      1st trimester pregnancy compared to the non-pregnant state. As compared to the
      1st trimester they described a slight reduction of LPA- and WGA-binding sites in
      the 3rd trimester. The most impressing changes of LPA and WGA binding sites in
      the extracellular matrix were observed during parturition. These results coincide
      with the authors' previous experience whereas the sialidase activity increases
      significantly during parturition. These data support the assumption that the
      terminal sialic acids and the sialidase play a recently yet not cleared role in
      the ripening of the human uterine cervix during pregnancy and in dilatation at
      the time of parturition.

PMID- 8290235
TI  - [Etiology of epidemic parotitis].
AB  - Blood samples of 204 acute parotitis patients in a fifteen month period (1991
      1992) were systematically examined for IgM, IgA, IgG antibodies of mumps and
      parainfluenza-virus 1, 2, 3 (PIV) by immunofluorescent test (IFT) and, in special
      cases several other virological examinations have been done. The etiological role
      of mumps-virus, parainfluenza-virus 1, 2, 3, one of the other viruses was
      confirmed in 76.0%, 1.5%, 6.3%, 1.5%, 4.9% of the cases, respectively. The
      etiology remained unknown in 9.8%. There were clinical symptoms of meningitis or
      orchitis in some and lymphadenopathy in several of the parainfluenza-virus caused
      parotitis patients. The authors conclude, that the parainfluenza-viruses are the
      second most frequent etiological agents of parotitis next to mumps-virus. They
      found that the Respiratory Syncytial Virus (RSV) also play etiological role in
      parotitis. This observation should be confirmed in the future by some other kind
      of virological tool too. The authors call attention to the difficulties and
      pitfalls of the virological serology in the infections caused by paramyxoviruses
      (PMV).

PMID- 8290236
TI  - [Comparative clinical study of Neopanpur and Creon].
AB  - The aim of the study was to compare the clinical efficacy of Neopanpur (EGIS) and
      Creon (Kalichemie) in patients with chronic pancreatitis. Fifteen patients were
      examined for 2 x 10 days. A period: Neopanpur 3 x 2, B period: Creon 10,000 3 x
      2. The type of the trial was: randomized, open, crossover study. The complaints
      of the patients (in score), the characters of the stool (daily weight, fat
      content, foamy, smell), amylum tolerance test (ATT), H2-breath test, lipjodol
      test, Lundh-test and Schilling-test were determined before and during the
      treatment periods. Both enzyme preparations could effectively decrease the
      anamnestic complaints, the stool frequency and characteristics together with the
      laboratory results of pancreatic functions. There is no clinically significant
      difference between the clinical efficacy of Creon and Neopanpur. Both enzyme
      preparations can be applied in the treatment of maldigestion in patients with
      chronic pancreatic insufficiency.

PMID- 8290237
TI  - [Relationship between selenium deficiency and high mortality and morbidity of
      cardiovascular diseases].
AB  - The authors consider the role of selenium deficiency to be of the utmost
      importance in the deteriorating health status of the Hungarian population. The
      pathophysiological processes occurring in selenium deficiency and possibly
      leading to cardio- and cerebrovascular diseases are discussed in detail. The
      results of human studies investigating the relationship between vascular diseases
      and selenium deficiency are summarized. It is concluded that selenium deficiency
      together with other harmful (prooxidant) effects may be responsible for the poor
      health status of the Hungarian population and therefore the importance of long
      term selenium supplementation in the prevention of such diseases is stressed.

PMID- 8290238
TI  - [Regional distribution of working physicians, diagnosed cases of depression and
      suicide mortality in Hungary].
AB  - Based on the well-known and strong relationship between suicide and depression,
      the authors investigated the regional distribution of the suicide rates, rates of
      diagnosed depressions and rates of working physicians in Hungary. It was found a
      strong significant positive correlation between the of working doctors and rate
      of diagnosed depressions, and both the mentioned parameters showed a strong
      significant negative correlation with the suicide rates. The more is the number
      of doctors/100,000 inhabitants, the better is the recognition of depression and
      the lower is the suicide rate in the given region. The rate of working doctors
      was significantly higher in the countries located in the western part of Hungary,
      which may have a role in the lower suicide mortality of this area of the country.

PMID- 8290239
TI  - [Intra-amnion infusion in the management of premature rupture of the membranes
      before the 28th week].
AB  - The authors applied intraamnial infusion in 5 cases altogether on account of the
      premature rupture of the membranes happened between the 25th-27th weeks. The
      pregnancies managed to be prolonged for 13-43 days. At present after 2 years, all
      the 4 survival children are alive and healthy. This method is advised to
      institutes with suitable conditions.

PMID- 8290240
TI  - [Sclerosing hemangioma of the lung].
AB  - The authors review the theories of origin of the so-called sclerosing heamangioma
      of the lung. The results of immunohistochemical studies--epithelial membrane
      antigen positivity and vimentin and factor VIII. related antigen negativity-
      support the hypothesis of epithelial origin. The problems of clinical and
      pathological differential diagnosis are discussed.

PMID- 8290241
TI  - [Experience with the molecular genetical detection of the chimera gene of the
      Philadelphia chromosome].
AB  - Molecular genetical techniques could be developed for detection of the chimera
      gene of Philadelphia chromosome or that of its gene product, due to the
      relatively conserved structure of the chimera gene. The authors successfully
      analysed 123 blood/bone marrow samples from 106 patients using these molecular
      techniques adapted from the literature. Patients were classified by the first
      diagnosis, 65 CML, 7 AML, 13 ALL patients were studied. 12 patients had the
      diagnosis of myeloproliferative syndrome, and 9 patients were after bone marrow
      transplantation. 57% of the total, and by diagnosis, 74% of CML, 28% of AML, 54%
      of ALL, and 33% of post-transplant samples have shown the chimera gene structure
      characteristic for Philadelphia chromosome. All patients of myeloproliferative
      syndrome were negative. In some cases the authors had the opportunity to study
      simultaneously the peripheral blood and the bone marrow sample of the same
      patient and of the same date. The ratio of the positivity of the two samples
      varied from one to infinite. The authors could follow the effect of interferon in
      one case, the change of clonality of the leukemic cell line in an other case.
      They had the opportunity to detect two different abnormal gene structures in the
      sample of an AML patient.

PMID- 8290243
TI  - [Treatment of trigeminal neuralgia with glycerin injected into Meckel's cavity].
AB  - The authors of the present study report on their results with glycerol gained
      over the past 9 years in 142 cases of trigeminal neuralgia. Initial pain relief
      was achieved in 64.5% of the cases. The average pain-free interval was 18.6 +/-
      5.4 months, in other terms, 50% of the patients remained pain-free at 15 months
      after the procedure. However, a half-life of 23 months could be observed in a
      subgroup of patients with typical neuralgia if glycerol injection was the only
      way of operation during the course of the disease. Facial sensory loss which
      persisted for more than one year was found in 9.6% of the patients, corneal
      hypaesthesia occurred in 5.7%. Despite the relatively frequent recurrences, the
      technical simplicity and the low rate of complications may render this method to
      be useful in the treatment of trigeminal neuralgia.

PMID- 8290242
TI  - [Use of Ceolat (dimethylpolysiloxan) chewing tablets in the preparation of
      patients for radiologic examinations].
AB  - Via statistic methods, the authors examine the capability of Ceolat tablet in
      improving the diagnostic efficacy of plain abdominal films, US and CT
      examinations. It has been proved on the basis of self-control examinations that
      by decreasing the amount of intestinal gas, Ceolat improves the quality of the
      images in all the three methods examined.

PMID- 8290244
TI  - [Treatment of empyema of the gallbladder by endoscopic drainage].
AB  - Medical history of an old female patient is described. Gallstones were extracted
      from the main bile duct after endoscopic papillotomy when she was 83 ys old.
      Eighteen months later, she presented an obstruction of the cystic duct with a
      consecutive empyema of gallbladder. The obstruction was relieved mechanically by
      inserting a catheter through guide-wire in the cystic duct and moving the
      impacted stone into the gallbladder. A naso-cholecystic drain was placed and kept
      in the gallbladder for six days to assure free passage of bile and to administer
      local antibiotic treatment. The patient quickly recovered, she has not presented
      any repeated cholecystitis or cholangitis in the last year. It was pointed out,
      that the endoscopic access to the gallbladder became possible. This technique
      offers an alternative way in the treatment of patients with high operative risk.

PMID- 8290245
TI  - [Splenic infarction and abscess as a complication of atrial fibrillation].
AB  - The case of a 64 year old man is presented by the authors whose spleen infarction
      developed in connection with atrial fibrillation was transformed into splenic
      abscess in spite of the applied conservative treatment. According to the
      overviewed literature the etiology, symptoms, diagnostic and therapeutic
      possibilities, as well as prognosis of these two entities related to spleen are
      described hereby.

PMID- 8290247
TI  - [Reflections on Chambers of Medicine].

PMID- 8290246
TI  - [Ales Hrdlicka (1869-1943), pioneer of anthropology].

PMID- 8290248
TI  - Interaction of hepatitis B virus X protein with a serine protease, tryptase TL2
      as an inhibitor.
AB  - X protein of hepatitis B virus (HBV) transactivates transcription of various
      viral and cellular genes. It has been suggested that X protein plays a major role
      in hepatocarcinogenesis by HBV. The protein possesses amino acid sequence
      homology to the functionally essential domain of Kunitz-type serine protease
      inhibitors. This Kunitz domain-like sequence in X protein is indispensable for
      the transactivation function. To clarify whether X protein has a serine protease
      inhibitor activity, a search was made for serine proteases which interact with,
      but not degrade X protein. Tryptase TL2, one of serine proteases in hepatic
      cells, was found to directly interact with X protein without degradation.
      Moreover, the activities of tryptase TL2 and an analogous protease were
      substantially inhibited by X protein. These results suggest that transactivation
      function of X protein is exerted by modulation of the hepatic serine protease
      activity, giving rise to quantitative or qualitative change of cellular
      transcription factor(s) through protection from proteolytic degradation and/or
      suppression of processing.

PMID- 8290249
TI  - Crosslinking of the surface immunoglobulin receptor in B lymphocytes induces a
      redistribution of neurofibromin but not p120-GAP.
AB  - The activation of Ras proteins is a key step in the signal transduction pathways
      triggered by ligand-bound cell surface receptors. The GTPase activating proteins
      (GAPs) p120-GAP and neurofibromin, the neurofibromatosis-type 1 (NF1) gene
      product, are thought to play an essential role in the regulation of Ras activity
      by increasing the GTPase activity of wild type, but not activated Ras in vitro.
      Both GAPs are widely expressed in mammalian tissues thus raising the question of
      whether or not they have different regulatory functions. In this study, we have
      analysed the distribution of p120-GAP and neurofibromin in splenic B lymphocytes
      by immunofluorescent staining. Crosslinking of surface immunoglobulin (slg), the
      B-lymphocyte antigen receptor, induced the redistribution of neurofibromin. In
      contrast, no apparent change in the cellular localization of p120-GAP occurred
      followed the cross-linking of slg. The redistribution of neurofibromin coincided
      both spatially and temporally with the relocalization of crosslinked slg and was
      inhibited by the cytoskeletal disrupting agents colchicine and cytochalasin D.
      These findings indicated that neurofibromin and p120-GAP can be differentially
      regulated in vivo and suggest that neurofibromin is a component of the signaling
      pathway initiated by crosslinking of B lymphocyte slg. Furthermore, our
      observations that cocapping neurofibromin with slg is independent of the p21ras
      redistribution suggests that the role of neurofibromin in B cells is not solely
      related to its ability to act as a Ras regulator.

PMID- 8290250
TI  - Functional interactions within adenovirus E1A protein complexes.
AB  - The transforming potential of adenovirus E1A oncogene products derives largely
      from the formation of complexes with cellular proteins, including the p105Rb
      tumor suppressor and a related p107 species, p130 and p300 proteins, and cyclin A
      (p60cycA). Extensive quantitative analyses using E1A deletion mutants identified
      unique binding patterns for each of these polypeptides within the amino terminus
      and conserved regions 1 and 2 (CR1 and CR2) of E1A proteins. A novel protein,
      termed p400, was found by peptide mapping to be related to p300, and, like p300,
      to require the E1A amino terminus and a portion of CR1 for binding. p130 was
      shown to be related to p107, and like p107, to associate with p60cycA. p107, p130
      and p105Rb all interacted primarily with CR2, however, sequences within CR1 and
      the amino terminus were capable of weak interactions and appeared to function
      cooperatively with CR2 to bind these proteins. Protein kinase activity present in
      E1A complexes probably derives at least in part from p60cycA-linked p33cdk2
      associated with p107 and p130. In vitro phosphorylation of complexes purified by
      immunoprecipitation resulted in labeling of several proteins. p60cycA was
      phosphorylated to about the same extent in cyclin A complexes prepared from
      either AD5- or mock-infected KB cells, however, that of p130 and p107 was
      dramatically higher in p60cycA complexes from infected cells. p300 was also
      phosphorylated in complexes prepared using E1A-specific antibodies. Thus one role
      of E1A proteins in signal transduction and regulation of the cell cycle may be to
      control the biological activity of p107, p130 and p300 by enhancing their
      phosphorylation through complex formation.

PMID- 8290251
TI  - Jun and Fos heterodimerize with ATFa, a member of the ATF/CREB family and
      modulate its transcriptional activity.
AB  - Three related clones encoding proteins (ATFa1, 2 and 3) with specific ATF/CRE DNA
      binding activities have been isolated from HeLa cell cDNA libraries. All three
      isoforms have weak effects on the basal activity of the adenovirus E2a promoter.
      We present evidence suggesting that a C-terminal element of the ATFa molecules
      negatively interferes with the intrinsic activation function of these proteins.
      We also show that coexpression of ATFa with c-Jun, Jun-B or Jun-D stimulates ATFa
      dependent reporter activity, while coexpression of c-Fos has no effect. Deletion
      analyses indicate that the metal-binding region of ATFa is dispensible for this
      effect, but that the domain comprising the leucine-zipper region of ATFa is
      required. Reciprocal co-immunoprecipitation experiments and electrophoretic band
      shift assays with in vitro synthesized proteins reveal direct interactions
      between ATFa and Jun or Fos. The ATFa/c-Jun heterodimers, but not the ATFa/c-Fos
      complexes, bind efficiently to ATF, CRE or AP1 sites. The detection of ATFa-Jun
      complexes in crude extracts from HeLa cells transfected with ATFa and c-Jun
      expression vectors suggests that such ATFa/c-Jun heterodimers also form in vivo.
      Altogether these results indicate that the ATFa proteins may contribute to the
      modulation of the activity of the Jun/Fos complexes by altering their DNA-binding
      and transcriptional properties.

PMID- 8290252
TI  - Elevated expression and activity of mitotic regulatory proteins in human
      papillomavirus-immortalized keratinocytes.
AB  - The E6 and E7 proteins of human papillomavirus (HPV) types 16 and 18 are
      expressed in cell lines derived from cervical cancers and can immortalize primary
      human keratinocytes. Since expression of E6/E7 has been shown to induce mitotic
      defects and karyotype instability in primary human cells, we investigated the
      effect of these viral oncoproteins on the expression and activity of mitotic
      regulatory proteins. Primary human keratinocytes immortalized by the entire
      genome or by only the E6/E7 genes of HPV types 16 and 18 displayed 5- to 20-fold
      increases in the abundance of p34cdc2, cyclin B and cyclin A when compared with
      normal parental cells. Results obtained from normal and immortalized cells that
      were derived from identical single donors were similar to those from mixed donor
      cultures. Increased protein levels were achieved without corresponding increases
      in mRNA, indicating alterations in translational and/or post-translational
      control. The histone H1 kinase activities associated with these regulatory
      proteins were also elevated, but to a lesser extent than the protein levels.
      Because p34cdc2, cyclin B and cyclin A regulate the entry into and exit from
      mitosis, increased expression and activity of these proteins could contribute to
      the mitotic defects and chromosomal aberrations associated with HPV-induced
      immortalization.

PMID- 8290254
TI  - Structural inferences of the ETS1 DNA-binding domain determined by mutational
      analysis.
AB  - The ets family of transcription factors is characterized by a conserved region
      that harbors the DNA-binding activity. We performed extensive deletion and
      mutational analyses, as well as DNA-peptide interaction studies necessary to
      identify the determinants of the DNA-binding activity of the ETS1 oncoprotein. We
      found that amino acids beyond the 85 amino acid conserved region are required in
      order to afford maximum DNA-binding activity in a heterologous system. Mutation
      throughout the binding domain can have a detrimental effect on binding activity,
      indicating that proper folding of the entire domain is necessary for DNA binding.
      A peptide, as small as 37 residues (K37N), derived from the basic region of the
      ETS1 binding domain, is sufficient to exhibit sequence-specific DNA recognition.
      Total randomization of Lysine 379, Lysine 381 and Arginine 391 within this region
      fails to provide functional substitutions, indicating that these specific amino
      acids within the basic region are required for binding. Transactivation activity
      of the ETS1 proteins bearing mutations was consistent with their DNA-binding
      activity, indicating that the primary (if not only) function of this domain is to
      provide sequence-specific DNA recognition activity. Our mutational analysis, as
      well as modeling predictions, lead us to propose a helix-turn-helix structure for
      the basic region of the ETS1 binding domain that is able to interact directly
      with DNA. We also propose that the hydrophobic alpha-helical region, surrounding
      tryptophan 338, is fundamental for proper protein folding and functioning of the
      ets binding domain.

PMID- 8290253
TI  - Dual control of myc expression through a single DNA binding site targeted by ets
      family proteins and E2F-1.
AB  - NIH3T3 cells expressing a mutant colony-stimulating factor-1 receptor (CSF-1R)
      containing a phenylalanine for tyrosine substitution in the tyrosine kinase
      domain at codon 809 exhibit defective myc regulation and do not enter S phase
      when stimulated by CSF-1. Enforced expression of either ets-1 or ets-2 in these
      cells restores their mitogenic response, albeit less efficiently than myc itself,
      suggesting that ets proteins may regulate c-myc expression. Ets-1 transactivates
      reporter genes driven by the human and mouse c-myc promoters through the binding
      site for the transcription factor E2F, the latter being required for E1A- and
      serum-induced c-myc expression. Analysis of E2F-1 sequences identified a minimal
      DNA binding domain that is related to those of ets proteins. Although E2F and ets
      proteins interact with similar consensus DNA binding sites, in vitro binding
      assays revealed that E2F can bind DNA as a homodimer, whereas ets proteins bind
      these sites as monomers. E2F and ets proteins do not form heterodimers in vitro
      and do not transactivate c-myc synergistically. Thus, E2F-1 and ets family
      members may independently regulate c-myc transcription through the same binding
      site at different times following growth factor stimulation.

PMID- 8290255
TI  - Detection of allelic losses on 17q12-q21 chromosomal region in benign lesions and
      malignant tumors occurring in a familial context.
AB  - A predisposing gene (BRCA-1) for breast and ovarian cancer has been located on
      chromosomal region 17q12-21. According to Knudson's hypothesis if this gene is a
      tumor suppressor gene, allelic losses would be found in tumors occurring in
      families with cancer aggregations. We studied 25 samples of both benign lesions
      and malignant tumors, from breast cancer site-specific families and other
      familial cancer aggregations. Allelic losses seem to be more frequent in tumors
      from breast site-specific families but also include the predisposing locus in
      other syndromes, suggesting a role of BRCA-1 in such families. Finding of allele
      losses near this locus in benign lesions suggests that such alterations may
      represent a first step in breast carcinogenesis. It is noteworthy that allele
      losses involve larger chromosome fragments in malignant tumors than in benign
      lesions where BRCA-1 is not lost, suggesting a similar mechanism for genomic
      deletion in the tumorigenesis of the colon and of the breast.

PMID- 8290256
TI  - Growth suppression of normal mammary epithelial cells by wild-type p53.
AB  - p53 mutations are frequent in human breast cancer. In order to understand the
      role of p53 in the context of the accumulation of mutations in breast cancer, a
      model of non transformed mammary cells was sought. The HC11 cells are
      immortalized, non transformed rodent mammary epithelial cells which synthesize
      milk proteins following stimulation with lactogenic hormones. p53 protein was
      readily detected in HC11 protein extracts with the PAb421 antibody. Two mutations
      were identified in the p53 cDNA from HC11 cells: a missense mutation at codon
      138, substituting Trp for Cys, and a microdeletion, codon 123 to 130, of exon 5.
      The latter results from an intronic mutation of the splice acceptor site at the
      intron 4/exon 5 junction. The mutations affect separate p53 alleles, and no wt
      allele was found. Wt p53 was introduced into HC11 cells by means of a retroviral
      vector, under the control of a Cd(++)-inducible promoter. In the presence of
      CdSO4 a dramatic growth inhibition was observed. A temperature-sensitive mutant
      p53 gene was also transfected into HC11 cells. This resulted in a marked
      inhibition of cells growth at 32 degrees C, when the p53 is in the wt
      conformation, while no effect was observed at 37 degrees C, when the mutant
      conformation is predominant. wt p53-mediated inhibition of monolayer growth does
      not involve induction of programmed cell death and does not activate de novo
      synthesis of differentiation-specific milk proteins. We conclude that mutations
      in the p53 gene likely played a role in their immortalization. The HC11 cells
      provide a model for assessing the cooperative action of other mutations in
      mammary tumorigenesis.

PMID- 8290257
TI  - Transforming activity of a newly cloned androgen-induced growth factor.
AB  - Our previous study demonstrated that androgen-dependent growth of mouse mammary
      carcinoma cells (SC-3) was mediated through an induction of heparin-binding
      growth factor, termed as androgen-induced growth factor (AIGF). Here, we report
      that NIH3T3 cells stably transfected with AIGF expression vector exhibit the
      abilities of tumor formation in nude mice, focus formation in monolayer culture
      and colony formation in soft agar. Thus, this newly cloned growth factor can be
      categorized as an oncogene. In addition, androgen-induced enhancement of DNA
      synthesis in SC-3 cells can be blocked by simultaneous incubation with AIGF
      antisense oligonucleotides. The possibility is also addressed that AIGF exerts
      its biological activity through an interaction with fibroblast growth factor
      (FGF) receptor. Transfection of expression vector encoding a variant form of FGF
      receptor-1 cloned from SC-3 cells into FGF receptor-negative L6 cells results in
      AIGF-dependent inhibition of differentiation. These results demonstrate that the
      ability of androgen to elicit transformed phenotype of SC-3 cells is mediated
      through AIGF induction and its interaction with FGF receptor-1.

PMID- 8290258
TI  - DNA bending by transcription factors CREM and CREB.
AB  - DNA bending is postulated to be a major determinant of gene expression and has
      been shown to be specifically induced by some regulatory proteins with DNA
      binding properties. Here we show that nuclear factors which naturally bind to
      CREs (cAMP-responsive elements) are able to induce bending in the sequences
      flanking this recognition site. In our assays we used a permutated binding
      site/gel retardation assay and bacterially generated nuclear factors. We have
      been studying the cAMP-responsive-element modulator (CREM) gene, which encodes
      both repressors (CREM alpha, beta and gamma) and an activator (CREM tau) of cAMP
      responsive transcription by alternative splicing. In addition, two alternative
      DNA-binding domains can be encoded in different CREM isoforms. No differences in
      induction of DNA bending by the CREM proteins with the two DNA binding domains
      were detected. The activator CREB induced DNA bending in a fashion similar to
      CREM. Importantly, we show that phosphorylation of CREM or CREB alters their
      mobilities in a regular gel shift assay as well as enhances the angle of DNA
      bending induced by these proteins.

PMID- 8290259
TI  - Subtraction cloning of H-rev107, a gene specifically expressed in H-ras resistant
      fibroblasts.
AB  - We have isolated by subtractive hybridization a novel gene, called H-rev107,
      which is specifically expressed in a phenotypic revertant of H-ras transformed
      208F rat fibroblasts. Apart from oncogene revertants, strong expression of H
      rev107 was found in REF52 and EK-3 cells, two fibroblast lines resistant to
      transformation by activated H-ras oncogenes. In contrast, transformation
      sensitive fibroblasts like 208F or NIH3T3 cells expressed only very little H
      rev107 RNA. In H-ras or v-src transformed fibroblasts, H-rev107 RNA was
      undetectable. Introduction of the adenovirus E1A nuclear oncogene into ras
      resistant REF52 cells abolished their transformation resistance and repressed the
      H-rev107 gene. H-rev107 encodes a protein with a molecular weight of 18 kDa
      without any structural similarity to known proteins. p18H-rev107 exists in two
      forms which can be distinguished by their electrophoretic mobility; one is
      localized predominantly in cell membranes, the other in the cytoplasm. In
      confluent contact-inhibited 208F cells, p18H-rev107 accumulated in cell
      membranes, while growth arrest induced by serum starvation did not induce H
      rev107. In REF52, cell density had no influence on the expression or localization
      of p18H-rev107. Repression of the H-rev107 gene may be closely associated with
      the loss of density-dependent growth inhibition and with the expression of the
      neoplastic phenotype.

PMID- 8290260
TI  - Isolation of two novel ras genes in Dictyostelium discoideum; evidence for a
      complex, developmentally regulated ras gene subfamily.
AB  - In Dictyostelium discoideum, three ras genes (rasD, rasG and rasB) and one ras
      related gene (rap1) have been previously isolated and characterized, and the
      deduced amino acid sequence of their predicted protein products share at least
      50% sequence identity with the human H-Ras protein. We have now cloned and
      characterized two additional members of the ras gene subfamily in Dictyostelium,
      rasC and rasS. These genes are developmentally regulated and unlike the
      previously isolated Dictyostelium ras genes, maximum levels of their transcripts
      were detected during aggregation, suggesting that the encoded proteins have
      distinct functions during aggregation. The rasC cDNA encodes a 189 amino acid
      protein that is 65% identical to the Dictyostelium RasD and RasG proteins and 56%
      identical to the human H-Ras protein. The predicted 194 amino acid gene product
      encoded by rasS is 60% identical to the Dictyostelium RasD and RasG proteins and
      54% identical to the human H-Ras protein. Whereas RasD, RasG, RasB and Rap1 are
      totally conserved in their putative effector domains relative to H-Ras, RasC and
      RasS have single amino acid substitutions in their effector domains, consistent
      with the idea that they have unique functions. In RasC, aspartic acid-38 has been
      replaced by asparagine (D38N), and in RasS, isoleucine-36 has been replaced by
      leucine (I36L). In addition, both proteins have several differences in the
      effector-proximal domain, a domain which is believed to play a role in Ras target
      activation. In RasC, there is a single conservative amino acid change in the
      canonical sequence of the binding site for the Ras-specific monoclonal antibody
      Y13-259, and consequently, RasC is less immunoreactive with the antibody than
      either of the Dictyostelium RasD or RasG proteins. In contrast, RasS, which has
      three substitutions in the Y13-259 binding site, does not react with the Y13-259
      antibody.

PMID- 8290261
TI  - Molecular characterization of RET/PTC3; a novel rearranged version of the
      RETproto-oncogene in a human thyroid papillary carcinoma.
AB  - The RET proto-oncogene encodes a transmembrane receptor of the tyrosine kinase
      family and has frequently been found activated in human thyroid carcinomas of the
      papillary subtype. In most cases the activation consisted of the fusion of its
      tyrosine-kinase domain with the 5'-terminal region of a gene designated H4 or
      D10S170. We have named the resulting H4/RET chimeric oncogene RET/PTC. Another
      activated form of the RET oncogene has subsequently been found in a thyroid
      carcinoma and is now referred to as RET/PTC2. Here we report the identification
      and cloning of a novel rearranged version of the RET oncogene in a human thyroid
      papillary carcinoma. In this case the tyrosine-kinase domain of RET was fused to
      a sequence 790 bp long belonging to a new gene that we have named RFG (RET Fused
      Gene). This novel chimeric oncogene has been designated RET/PTC3. In order to
      have more insights into the function of RFG we have completely cloned and
      sequenced its cDNA. RFG predicted amino-acid sequence does not have any
      significant homology to any already known genes and is ubiquitously expressed in
      human and mouse tissues. Finally we provide evidence indicating that the
      rearrangement leading to the generation of RET/PTC3 occurred in vivo in the
      original tumor DNA.

PMID- 8290262
TI  - The PDGF receptor alpha subunit activates p21ras and triggers DNA synthesis
      without interacting with rasGAP.
AB  - There are two closely related, but distinct platelet-derived growth factor
      receptor (PDGFR) subunits: alpha and beta. Recent studies have indicated that
      relay of a biological signal from the activated PDGFR beta subunit is determined
      to a large degree by the intracellular signal transduction enzymes with which the
      beta subunit associates. Like the beta subunit, the PDGFR alpha subunit encodes a
      tyrosine kinase that is activated and tyrosine phosphorylated upon binding of
      PDGF. To investigate the mechanism by which the PDGFR alpha subunit mediates
      signal transduction, we examined the proteins that associate with the activated
      PDGFR alpha subunit. The human alpha subunit was expressed in PhB cells,
      fibroblasts derived from Ph/Ph mouse embryos, which express the beta subunit but
      do not express the PDGFR alpha subunit. In response to binding of PDGF, the alpha
      subunit stably associated with phospholipase C gamma 1 (PLC-gamma 1),
      phosphatidylinositol 3 kinase (PI3K), the phosphotyrosine phosphatase Syp, and a
      120 kd protein. These same proteins were detected binding to the activated PDGFR
      beta subunit. Unlike the PDGFR beta subunit, the PDGF-activated alpha subunit did
      not stably associate with the GTPase activating protein of ras (rasGAP), nor did
      it mediate tyrosine phosphorylation of rasGAP. Despite its apparent inability to
      interact with rasGAP, the alpha subunit was fully able to trigger PDGF-dependent
      p21ras activation and DNA synthesis. We conclude that the PDGFR alpha subunit
      does not mediate tyrosine phosphorylation or associate with ras-GAP, and that
      these events are not required for PDGF-AA-mediated activation of p21ras or DNA
      synthesis.

PMID- 8290263
TI  - The cis-acting elements known to regulate c-myc expression ex vivo are not
      sufficient for correct transcription in vivo.
AB  - Much of our knowledge about the regulation of the c-myc proto-oncogene expression
      has come from studies of c-myc gene expression in several well defined ex vivo
      systems, including differentiation systems and tumor cells. However, very few
      investigations have been performed to determine the factors and cis-acting
      sequences that regulate c-myc expression in vivo. In order to obtain information
      on the sequences required to regulate c-myc gene transcription from the two major
      P1 and P2 initiation sites in the mouse, we have generated several constructs
      containing human or murine c-myc genomic sequences with various 5' flanking
      sequences and derived corresponding transgenic mice. A sensitive S1 nuclease
      protection assay was performed to analyse and to compare transgene expression
      with that of the endogenous c-myc mRNA, either in adult organs, or during
      development. None of the transgenic mice expressed the construct appropriately,
      although several strains exhibited unexpected expression most probably due to
      position effects. Our results indicate that the cis-acting elements described to
      regulate c-myc expression ex vivo are not sufficient to drive the correct
      expression of c-myc gene in vivo and strongly suggest that additional regulatory
      elements located upstream from -3500 (with respect to mouse P1 promoter) and
      downstream 1500 bp from polyadenylation sites are required.

PMID- 8290264
TI  - Phosphorylation of the SHC proteins on tyrosine correlates with the
      transformation of fibroblasts and erythroblasts by the v-sea tyrosine kinase.
AB  - The S13 avian erythroblastosis viral genome encodes an oncogenic tyrosine kinase,
      termed env-sea, that is capable of transforming fibroblasts and erythroblasts.
      Although the tyrosine kinase activity of the env-sea protein has been shown to be
      necessary for transformation, no substrates for this enzyme have been detected in
      vivo. Here we demonstrate that the recently described shc proteins are
      phosphorylated on tyrosine residues in both S13 transformed fibroblasts and
      erythroblasts. Furthermore, using an S13 temperature sensitive mutant, we show
      that the phosphorylation of the shc proteins occurs concomitantly with the
      activation of the tyrosine kinase activity of the env-sea protein. These
      observations make the phosphorylation of the shc proteins a good candidate for
      being involved in oncogenic signaling by the env-sea oncoprotein.

PMID- 8290265
TI  - The PML-RAR alpha gene product of the t(15;17) translocation inhibits retinoic
      acid-induced granulocytic differentiation and mediated transactivation in human
      myeloid cells.
AB  - Acute promyelocytic leukemia (APL) is characterized by an arrest of granulocytic
      differentiation and a reciprocal t(15;17) translocation fusing the PML gene to
      the retinoic acid receptor alpha (RAR alpha) gene. PML was recently identified as
      a potential transcription factor. In non hematopoietic cells, the transfected PML
      RAR alpha product binds all trans retinoic acid and exhibits altered
      transactivating properties when compared with RAR alpha. A major question raised
      by these observations is whether PML-RAR alpha contributes to the inhibition of
      myeloid differentiation. We find that in myeloid cell lines responsive to
      retinoic acid, PML-RAR alpha blocks retinoic acid mediated transactivation and
      totally abrogates the retinoic acid mediated granulocytic differentiation. These
      findings strongly suggest that PML-RAR alpha may, by blocking normal retinoic
      acid dependent myeloid differentiation, participate in the leukemogenesis of APL.
      The fact that high doses of all-trans retinoic acid relieve the inhibitory effect
      of PML-RAR alpha corroborates the therapeutic effect of all-trans retinoic acid
      in APL patients.

PMID- 8290266
TI  - A highly sensitive assay for mutant ras genes and its application to the study of
      presentation and relapse genotypes in acute leukemia.
AB  - Most studies of ras oncogene activation use assays for ras mutations based on the
      polymerase chain reaction (PCR) of DNA segments containing ras exons 1 and 2,
      followed by allele-specific oligonucleotide (ASO) hybridization or direct
      sequencing, which require that to be detectable, a mutation must be present in at
      least 3-25% of ras alleles. Thus, studies of tissues in which only a fraction of
      cells contains a ras mutation risk false negative results. To minimize this risk,
      we have developed a highly sensitive, non-radioactive assay for ras mutations.
      Ras genes were PCR-amplified using mismatched primers, to introduce restriction
      sites into products derived from normal alleles. Repeated restriction digestion
      and PCR enriched for mutant alleles, visualized by agarose gel electrophoresis.
      Serially diluted DNA samples containing ras mutations demonstrated detection of 1
      mutant/10(6) normal alleles (four orders of magnitude more sensitive than PCR/ASO
      hybridization). This assay was applied to DNA from four patients with relapsed
      acute leukemia in whom ras mutations present at diagnosis were not detectable by
      PCR/ASO hybridization at relapse. In one case, the mutation present at diagnosis
      was demonstrated at relapse. In the others, loss of the mutation was confirmed,
      at a greatly increased sensitivity. This method is widely applicable to detection
      of mutant ras alleles admixed with larger numbers of normal alleles.

PMID- 8290267
TI  - Induction of AP-1 (Fos/Jun) by chemical agents mediates activation of glutathione
      S-transferase and quinone reductase gene expression.
AB  - A regulatory element, EpRE, was found to be responsible for the induction of
      mouse glutathione S-transferase (GST) Ya gene expression by a variety of chemical
      agents such as planar aromatic hydrocarbons, diphenols, phorbol ester,
      phenobarbital and electrophilic compounds. The EpRE is composed of two adjacent
      AP-1-like binding sites and was recently found to be activated by Fos/Jun
      heterodimeric complex (AP-1). In this report we show that regulatory elements
      ARE, previously demonstrated to mediate the chemical induction of rat GST Ya and
      quinone reductase genes, have a similar structure with EpRE and are activated by
      Fos/Jun complex. The activation of GST Ya and quinone reductase genes by a
      variety of chemical inducers is found to be associated with an increase in AP-1
      binding activity. We present evidence that chemical agents induce expression of c
      fos and c-jun proto-oncogenes and an enhanced synthesis of protein components of
      AP-1 complex. We suggest that the increased synthesis of AP-1 complex followed by
      an AP-1-mediated transcriptional activation of GST Ya and quinone reductase genes
      may provide a molecular mechanism for the induction of these drug-metabolizing
      enzymes by chemical agents.

PMID- 8290268
TI  - Characterization of a functional promoter for the Xenopus wnt-1 gene on vivo.
AB  - The Xenopus homolog of the proto-oncogene wnt-1 (int-1) is transiently expressed
      during neurula and tailbud stages of early development. To determine the
      mechanisms involved in the transcriptional regulation of the Xwnt-1 gene, we
      isolated Xwnt-1 genomic sequences. The promoter activity of the 5' flanking
      region of the gene was analysed by microinjection of chimeric luciferase reporter
      constructs into embryos. It is shown that the proximal 220 bp of the Xwnt-1
      promoter is able to confer activation of the reporter gene at the early neurula
      stage. DNaseI footprinting analysis of the proximal promoter region with nuclear
      protein extracts from neurula stage embryos revealed five protein binding
      regions. Deletion and mutation analysis shows that one of these five protein
      binding regions is essential for promoter activity. Gel shift experiments
      indicate that a sequence element resembling the GT-I and GT-II motifs of the SV40
      enhancer is important for the Xwnt-1 promoter activity in vivo.

PMID- 8290269
TI  - Antisense transcripts and protein binding motifs within the Wilms tumour (WT1)
      locus.
AB  - Transcription of the WT1 locus is restricted, both temporally and spatially, to a
      subset of epithelial cells in mammalian kidneys and gonads. WT1, one of the two
      divergent transcripts mapping to this locus encodes a zinc finger protein that is
      likely a transcriptional regulator. The other transcript, WIT1, encodes a product
      of unknown function that is subject to alternate splicing in the region
      immediately 5' of the WT1 gene. Analysis of the 5' end of this locus further
      revealed the presence of multiple transcriptional start sites for both genes,
      such that some of the WIT1 transcripts are encoded by the antisense strand of the
      first exon of WT1. The genomic region surrounding the transcriptional start sites
      appears to constitute part of a bi-directional promoter based on the ability of a
      DNA fragment derived from this region to direct expression of a chimeric CAT gene
      construct in transient transfection assays. Discrete sequences within the region
      are capable of interaction in vitro with nuclear extracts derived from a variety
      of rat and mouse tissues. Interestingly, recombinant WT1, representing the
      product of zinc finger region of the most abundant of the four alternatively
      spliced transcripts, is also capable of binding to sequences within this region.

PMID- 8290271
TI  - Tumour incidence, spectrum and ploidy in mice with a large deletion in the p53
      gene.
AB  - In human tumourigenesis the tumour suppressor gene most commonly affected by
      mutation, inactivation or allele loss is p53. Loss of p53 function is associated
      both with failure to maintain a normal diploid status and inability to delete
      cells by apoptosis following DNA damage. To investigate further the role of p53
      we have generated mice carrying a large deletion within the gene. All animals
      homozygous for this deletion develop spontaneous tumours, predominantly
      lymphomas, by the age of 6 months. 10% of heterozygotes develop a range of
      neoplasms, with a lower predisposition towards lymphoma, by 9 months. Both tumour
      incidence and spectrum in heterozygotes differ from those previously reported in
      another p53 mutant stock, suggesting either difference in exposure to carcinogens
      between the two stocks, or a role for modulating genes within different genetic
      backgrounds. Tumours showed frequent loss of diploid status, and the majority of
      those arising in heterozygotes showed loss of the wild type allele. These
      findings are consistent with the concept that p53 acts as a tumour suppressor by
      preventing the propagation of DNA damage to daughter cells.

PMID- 8290270
TI  - The non-catalytic domain of ras-GAP inhibits transformation induced by G protein
      coupled receptors.
AB  - We have studied the relationship between ras-GAP and G protein coupled receptors
      in a proliferative setting comprised of NIH3T3 expressing transfected muscarinic
      receptors (mAChRs). GAP expression plasmids were engineered to encode wild-type
      GAP, its carboxyl-terminal catalytic domain, a mutant lacking a portion of the
      catalytic domain, and an amino-terminal domain which contained the hydrophobic
      region as well as SH2-SH3 domains. Cotransfection of each GAP expression plasmid
      into NIH3T3 cells did not affect the transforming ability of the v-mos oncogene,
      but plasmids encoding wild-type GAP or the mutant consisting of an intact
      catalytic domain inhibited transformation induced by normal c-ras. Wild-type GAP
      also prevented transformation by m1 mAChRs, whereas the mutant consisting of only
      its catalytic domain lacked any demonstrable effect. In contrast, the N-terminal
      non-catalytic domain of GAP effectively prevented m1-induced focus-formation.
      Cell lines coexpressing m1 receptors and each of the GAP constructs revealed that
      GAP proteins do not affect m1 receptor density, receptor ligand binding
      characteristics or coupling to the PI-PLC signal transduction pathway. Thus, our
      findings suggest a role for the N-terminal non-catalytic domain of GAP in
      regulating biological functions mediated by G protein-coupled receptors.

PMID- 8290272
TI  - Aberrant upregulation of a novel integrin alpha subunit gene at 3p21.3 in small
      cell lung cancer.
AB  - Our recent identification of homozygous deletions at 3p21.3 in lung cancer has
      provided further support for the presence of a tumor suppressor gene in this
      chromosomal region. As a part of our efforts for positional cloning of a tumor
      suppressor gene at 3p21.3, we have characterized a transcriptional unit within
      this region using genomic fragments with interspecies conservation. The
      identified gene was found to encode a novel integrin alpha subunit, termed alpha
      RLC, which is closely related to alpha 4 in structure but clearly different from
      alpha 4 in its expression pattern in the physiological and pathological setting
      of the lung. This finding and the exact localization of the gene suggest that it
      is a good candidate for a tumor suppressor gene in lung cancer, but our extensive
      search covering one third of the gene did not reveal any somatic mutations within
      the coding region. Interestingly, however, alpha RLC was abundantly expressed in
      fetal lung and lung cancers, particularly small cell lung cancers (SCLC). Its
      aberrant upregulation in the SCLC samples, both cell lines and primary tumors,
      which might have been caused by a yet unidentified mutations or by deletions of
      other gene, and its homology to alpha 4, which is thought to play a role in
      metastasis, suggest that altered alpha RLC expression may contribute to the
      acquisition of malignant phenotypes of this type of lung cancer.

PMID- 8290273
TI  - Novel human oncogene lbc detected by transfection with distinct homology regions
      to signal transduction products.
AB  - In order to isolate transforming genes involved in leukemias, DNA from a CML
      acute phase sample was transfected into NIH-3T3 cells and found to be tumorigenic
      in nude mice. Partial genomic cloning using human repeat sequence as probe
      followed by cDNA cloning of this oncogene, termed lbc, was undertaken. The lbc
      cDNA sequence shows no identity to known proteins and codes for a predicted
      hydrophilic protein product of 47 kD, which contains several consensus kinase
      phosphorylation sites. The N-terminus encodes a consensus E-F hand motif followed
      by a region of homology to the transforming human oncogene dbl associated with
      regulatory activity for the ras superfamily of small G proteins, while the C
      terminus contains homology with pleckstrin and rac protein kinase in a region
      which overlaps with the recently defined PH (pleckstrin homology) domain. Lbc
      expression is restricted to human hematopoietic cells and skeletal muscle, lung
      and heart. Transfection of 3T3 cells with an expression vector encoding lbc cDNA
      results in focus formation, demonstrating its biological activity. These data
      indicate that the lbc oncogene encodes a novel product implicated in distinct
      cellular signal transduction functions.

PMID- 8290274
TI  - DNA damage induced p53 mediated transcription is inhibited by human
      papillomavirus type 18 E6.
AB  - Cervical cancer is similar to other human cancers in that it develops through a
      multistep process. However, infection with oncogenic human papillomaviruses
      (HPVs) is believed to be essential for the initiation of this disease. Although
      HPV may play a central role in the early stages of neoplasia, the accumulation of
      mutations in an assortment of genes precedes the development of malignant
      cervical carcinoma. The mechanisms by which abnormalities accumulate are various,
      but it is possible that viral proteins are involved. In particular, the viral E6
      oncoprotein has been shown to interact with the cellular tumour suppressor
      protein p53, which is involved in DNA damage repair pathways. Hence, E6 may
      contribute to the genomic instability through this interaction with p53. We have
      tested this hypothesis by monitoring the effects of E6 upon DNA damage induced
      p53 transcriptional activity. This study shows that HPV-18 E6 inhibits p53
      transcriptional activity following genotoxic stress with UV radiation. No effect
      was observed when a mutant E6 unable to direct the degradation of p53 was
      included in this assay. These results suggest that continued E6 expression may
      contribute to the accumulation of DNA damage associated with the progression of
      cervical cancer.

PMID- 8290275
TI  - Genomic loci of human mitogen-activated protein kinases.
AB  - Mitogen-activated protein (MAP) kinases [also known as Erks] have been
      established to function as important mediators of signal transduction by growth
      factor receptors. Several components of the MAP kinase signal transduction
      pathway have been demonstrated to be oncogenically activated in malignant tumors.
      These include growth factor receptors, the GTP-binding protein Ras, and the
      protein kinase Raf. The genes that encode MAP kinases therefore represent
      potential targets of carcinogenic insults. Here, we report the genomic loci of
      three MAP kinase genes are widely distributed within the human genome: p41mapk
      (Erk2) at 22q11.2; p44mapk (Erk1) at 16p11.2; and p63mapk (Erk3-related) at 18q12
      21.

PMID- 8290276
TI  - Membrane ruffling and chemotaxis transduced by the PDGF beta-receptor require the
      binding site for phosphatidylinositol 3' kinase.
AB  - Activation of the platelet-derived growth factor (PDGF) beta-receptor results in
      motility responses in the forms of membrane ruffling and chemotaxis. Porcine
      aortic endothelial cells expressing the PDGF beta-receptor or a chimeric
      fibroblast growth factor (FGF) receptor, in which the endogenous kinase insert
      was replaced with the corresponding region from the PDGF beta-receptor, migrated
      efficiently towards a concentration gradient of PDGF-BB and bFGF, respectively,
      and exhibited both pronounced edge ruffling and circular membrane ruffling in
      response to ligand-stimulation. The wildtype FGF receptor-1 showed weak or no
      response in these assays. Further analyses were conducted on mutant receptors, in
      which tyrosine residues that can serve as autophosphorylation sites and thereby
      mediate interactions with specific signal transduction molecules, were changed to
      phenylalanine residues. Each one of the analysed mutants were mitogenically
      active, however, a mutant in which Tyr740 and Tyr751 were replaced failed to
      mediate ruffling and chemotaxis. These two residues are implicated in the binding
      of phosphatidylinositol 3' kinase. The notion that this enzyme is involved in
      PDGF beta-receptor-induced cell motility is furthermore supported by the finding
      that another mutant, in which Met743 and Met754 were replaced, and which failed
      to interact with phosphatidylinositol 3' kinase, was also unable to mediate
      motility responses.

PMID- 8290277
TI  - Structural analysis of the chicken max gene.
AB  - The recent identification of Max, a nuclear phosphoprotein that dimerizes with
      members of the Myc protein family, has provided an additional tool to examine the
      role of the Myc oncoprotein as a sequence-specific DNA binding protein and a
      potential regulator of gene transcription. Here we report the nucleotide sequence
      of an avian max gene isolated from a lambda EMBL3 genomic library prepared from
      size-selected chicken embryo fibroblast DNA. The complete transcription unit
      encoding chicken Max is contained on a 5.7 kbp BglII DNA fragment which expresses
      an appropriately sized max mRNA of 1.5 kb following transfection of C3H10T1/2
      mouse fibroblasts. The coding region of the chicken max gene is organized into
      five exons and the overall identity between the human and chicken max coding
      sequences is 85% at the nucleotide level and 96% at the amino acid level. The
      basic helix-loop-helix/leucine zipper region, the casein kinase II
      phosphorylation sites and the nuclear localization signal sequence are 100%
      conserved in all vertebrate Max proteins characterized to date. DNA sequence
      analysis of the 5' flanking region of the chicken max coding sequence reveals the
      absence of consensus TATA or CAAT motifs, but the presence of numerous GC-rich
      sequences that are typical in eukaryotic genes which are expressed constitutively
      in different tissues and under different growth conditions.

PMID- 8290278
TI  - Mapping of two genes encoding members of a distinct subfamily of MAX interacting
      proteins: MAD to human chromosome 2 and mouse chromosome 6, and MXI1 to human
      chromosome 10 and mouse chromosome 19.
AB  - Both the MAD and the MXI1 genes encode basic-helix-loop-helix-leucine zipper
      (bHLH-Zip) transcription factors which bind Max in vitro, forming a sequence
      specific DNA-binding complex similar to the Myc-Max heterodimer. Mad and Myc
      compete for binding to Max. In addition, Mad has been shown to act as a
      transcriptional repressor while Myc appears to function as an activator. Mxi1
      also appears to lack a transcriptional activation domain. Therefore, Mxi1 and Mad
      might antagonize Myc function and are candidate tumor suppressor genes. We report
      here the mapping of the MAD and MXI1 genes in human and mouse by fluorescence in
      situ hybridization (FISH) and by recombination mapping. The MAD gene was mapped
      to human chromosome 2 at band p13 by FISH and to mouse chromosome 6 by meiotic
      mapping. The MXI1 gene was mapped to human chromosome 10 at band q25 and on mouse
      chromosome 19 at region D by FISH. There was a second site of hybridization on
      mouse chromosome 2 at region C, which may represent a pseudogene or a related
      sequence. The mapping results confirm regions of conservation between human
      chromosome 2p13 and mouse chromosome 6 and between chromosome 10q25 and mouse
      chromosome 19D. Human chromosomes 2p13 and 10q25 have been involved in specific
      tumors where the role of Mad and Mxi1 can now be investigated.

PMID- 8290279
TI  - Differentially spliced erg-3 product functions as a transcriptional activator.
AB  - ets oncogene superfamily consists of a family of transcriptional factors that
      functions as activators and/or repressors. Previously, we have identified a
      member of this ets superfamily namely erg, ets related gene. erg gene was shown
      to code for at least two proteins erg-1 and erg-2 because of alternative splicing
      and alternative usage of initiation codon. In this report we show that erg gene
      codes for an additional erg variant protein, erg-3 as a result of differential
      splicing which results in the insertion of 24 amino acids in the coding region of
      erg-2 protein. RNAase protection analysis revealed that erg-3 transcripts are
      expressed in a variety of cells. Erg-3 was also found to activate the
      transcription of the reporter TK-CAT gene linked to erg target sequences
      suggesting that erg-3 codes for a sequence specific transcriptional activator.

PMID- 8290280
TI  - Fungal infections of the nose and paranasal sinuses. Part I.
AB  - This article details the incidence, etiology, classification, and radiographic
      findings of fungal infections. Major infections discussed include aspergillosis,
      mucormycosis, blastomycosis, candidiasis, chromblastomycosis, coccidioidomycosis,
      histoplasmosis, paracoccidioidomycosis, and rhinosporidiosis.

PMID- 8290281
TI  - Fungal infections of the nose and paranasal sinuses. Part II.
AB  - This article, the second of two, examines the following infections in detail:
      phaeohyphomycosis, bipolaris infections, Exserohilim infections, multiple-fungal
      infections, allergic dematiaceous sinusitis, Pseudallescheria infections,
      sporothricosis, basidoiomycetous infections, Paecilomyces infections,
      penicilliosis, Cryptococcus infections, and others.

PMID- 8290282
TI  - Fungal infections of the oral cavity.
AB  - Although several strains of Candida can infect the oral mucosa, the most commonly
      encountered oral fungal infection is Candida albicans, which may be highly
      infective because of its greater level of pathogenicity and adherence properties.
      C. albicans is an oral commensal in as many as 40% to 65% of healthy adult
      mouths. The papillated dorsal surface of the tongue and palatal mucosa beneath a
      maxillary denture are favored reservoir sites. Oral candidal infection almost
      always involves a compromised host. The compromise may be local or systemic.
      Local factors include decreased salivation and the weaning of dentures. Systemic
      factors include diabetes mellitus, pernicious anemia, and AIDS. Some have even
      implicated advanced age and the female gender as being mild predisposing factors.
      Furthermore, the C. albicans infection itself can depress a host's immune system.
      A patient with oral candidiasis can present with one or more of the following
      clinical forms: pseudomembranous, erythematous, hyperplastic, and denture
      erythematous. Many investigators accept median rhomboid glossitis as a form of
      chronic oral candidiasis. In some patients with angular cheilitis, genesis of the
      lesions is secondary to monilial infestation. Because C. albicans is a normal
      inhabitant in many mouths, diagnostic confirmation of infection often rests with
      successful response (i.e., resolution of lesions) to antifungal medications. This
      form of diagnostic confirmation can be further enhanced by culturing the
      offending microbe, preparing a fungal smear, or even incisional biopsy. The
      microscopic demonstration of fungal hyphae is highly diagnostic of the candidal
      infection, whether the hyphae are demonstrated on a PAS smear or on a biopsy
      within surface stratified squamous epithelium. Numerous medications exist for the
      treatment of oral candidiasis. They include the antibiotic nystatin as well as
      clotrimazole, ketoconazole, and fluconazole. Nystatin is safe and is used as a
      topical agent in rinse or pastille forms. Clotrimazole is used as a topical agent
      in lozenge form; it is highly effective but can cause liver enzyme changes.
      Ketoconazole, which is usually prescribed systemically, is highly effective but
      also capable of causing adverse liver changes. Chlorhexidine can be used as an
      oral rinse or as a disinfectant for dentures.

PMID- 8290283
TI  - Fungal infections of the larynx.
AB  - Some generalizations regarding fungal infections of the larynx can be made. The
      reader is cautioned to refer to discussions of the individual infections for
      exceptions to these generalizations. For the most part, the mycoses are organisms
      of low pathogenicity emerging as opportunistic organisms thriving in a
      compromised host. The isolated fungal infections of the larynx reported are
      exceptions to the rule. Involvement of the larynx and other body sites outside
      the lung generally indicates a widely disseminated form of the disease. Fungal
      infections most commonly occur in the immunocompromised patient, including those
      afflicted with AIDS, cancer, leukemia, and other lymphoreticular neoplasms,
      patients on long-term corticosteroid therapy, patients with chronic systemic
      diseases, including diabetes mellitus and severe pulmonary disease, and patients
      who have undergone successful organ transplantation, which depends on immunologic
      suppression. Although specific fungi are characteristically found in designated
      endemic areas, the diseases may surface in remote areas in persons who have
      recently traveled through the endemic sites. The pathologic picture can be
      confusing, and pseudoepitheliomatous changes at times resemble malignancy. When
      atypical features occur in a patient with a suspicious history, special stains
      and cultures as well as skin tests and serologic studies may be helpful in
      establishing the diagnosis. For the most part, amphotericin B has been the
      mainstay of therapy, although the introduction of the newer azole drugs
      (ketoconazole, itraconazole and fluconazole) may present a breakthrough in the
      future therapy of these lesions. Ketoconazole has been proven efficacious in
      certain fungal infections. Itraconazole has recently been released for clinical
      use. Because of its lower incidence of toxic side effects, it may replace
      ketoconazole in the therapy of these diseases. Finally, fluconazole, taken
      orally, effectively crosses the blood-brain barrier; appropriate clinical trials
      may prove it to be an acceptable agent for those fungi commonly affecting the
      central nervous system.

PMID- 8290284
TI  - General principles of management of fungal infections of the head and neck.
AB  - The adequate management of fungal infections of the head and neck revolves around
      five major principles: Timely diagnosis, usually dependent on a high index of
      suspicion; Control of local and systemic predisposing factors; Surgical
      debridement geared to the level of invasiveness of the fungus; Pharmacotherapy of
      the appropriate type, route of administration, and dosage; Long-term follow-up.
      Preventive measures, although typically out of the hands of otolaryngologists,
      should be instituted as feasible by the medical community at large.

PMID- 8290285
TI  - Antifungal agents and the treatment of fungal infections of the head and neck.
AB  - Recommendations for the treatment of fungal pathogens are undergoing rapid
      reevaluation with the availability of many new therapeutic agents. This article
      reviews the basic pharmacology of anti-fungal agents and their applications in
      the treatment of infectious syndromes in the head and neck.

PMID- 8290286
TI  - Basic mycology underscoring medically important fungi.
AB  - This article details the basic mycologic features of yeast and mold-like fungi
      causing infections in humans. Concordant with the mycologic attributes
      delineating species identification, the pathogenic potential of mycotic agents is
      discussed with particular reference to intrinsic fungal virulence factors (e.g.,
      exoenzymes) and host factors (e.g., neutrophil function, underlying disease)
      predisposing to colonization and infection.

PMID- 8290287
TI  - Host factors in human fungal infections.
AB  - This article discusses mechanisms of host resistance to fungal infection and
      those conditions, both natural and iatrogenic, that predispose to fungal
      infection. Specific topics discussed include barrier defenses, bacterial
      antagonism, nonimmune host factors, cellular and humoral immunity, and underlying
      and iatrogenic medical conditions.

PMID- 8290288
TI  - Histopathology of sinonasal fungal disease.
AB  - 1. To increase diagnostic yield, the otolaryngologist should convey suspicions of
      mycotic sinus disease to the pathologist. 2. Fungal cultures are a necessary
      adjunct to histopathologic identification. 3. Any sinonasal chronic inflammatory
      or granulomatous sinus process, or allergic process, may have a fungal etiology,
      even with negative GMS stains. 4. The diagnosis of sinonasal "inflammatory
      pseudotumor" should be accepted with some reservation, as it may represent an
      unrecognized sinonasal mycotic process. 5. Aspergillus spp. may be definitively
      identified histologically in sinonasal mycetomas and in invasive disease. When
      only fragments of thin septate hyphae, are found, one cannot assume they always
      belong to Aspergillus. 6. One must not assume that all wide "pleomorphic" hyphal
      fragments belong to Rhizopus or, for that matter, Zygomycetes. 7. Candida,
      Pseudoallescheria, Rhinosporidium and Cryptococcus are rare sinonasal pathogens
      that may also be positively identified morphologically.

PMID- 8290289
TI  - Imaging of paranasal sinus fungal disease.
AB  - If a patient presents with a history and clinical findings suggestive of an
      inflammatory process, the sectional imaging examination of choice should be a CT
      scan. This study will minimize the chances of diagnostic error as described.  MR
      imaging can be done to complement the CT scan in selected cases when additional
      information from such an MR image will contribute to management. In the final
      analysis, the radiologist today can give precise anatomic localization of
      pathology on a scale never before possible. It is the pathologist, however, who
      still must make the final diagnosis.

PMID- 8290290
TI  - Fungal infections of the external ear.
AB  - Fungal infections of the external auditory canal can pose a great clinical
      challenge both in diagnosis and in therapy. Most infections present in patients
      who have undergone previous medical treatment of the external canal, which has
      changed the pH and normal canal flora, or in those who have diminished capacity
      for resisting infections. Diagnosis is made by clinical inspection and selective
      cultures. Therapy consists of complete cleaning followed by use of topical
      antimycotic agents. Systemic therapy is rarely required.

PMID- 8290291
TI  - Kanamycin depletes cochlear polyamines in the developing rat.
AB  - Developing mammals are more sensitive to aminoglycoside antibiotics and other
      ototoxic agents than adults, with maximum sensitivity occurring during the period
      of anatomic and functional maturation of the cochlea. For the aminoglycoside
      antibiotics, the hypersensitive period in rats occurs during the second and third
      postnatal weeks. Toxicity is initially expressed as outer hair cell (OHC) damage
      in the high-frequency, basal region of the cochlea. Distortion-product
      otoacoustic emissions (DPOAEs), physiologic measures of OHC function, are
      particularly sensitive to aminoglycoside exposure during the period of rapid
      cochlear physiologic development. Toxicity is characterized by increased DPOAE
      thresholds and decreased amplitudes. The mechanism of developmental sensitivity
      to aminoglycosides is unknown. A potential biochemical target of aminoglycosides
      is the ornithine decarboxylase (ODC)-polyamine pathway. ODC activity is elevated
      in the developing rat cochlea, aminoglycosides inhibit cochlear ODC in developing
      rats, and alpha-difluoromethylornithine (a specific ODC inhibitor) impairs
      development of cochlear function. In the present study we demonstrate an
      incomplete polyamine response to aminoglycoside damage, characterized by
      inhibition of the polyamines spermidine and spermine and accumulation of
      putrescine in the organ of Corti. Aminoglycoside inhibition of polyamine
      synthesis may mediate developmental ototoxic hypersensitivity by interfering with
      developmental and repair processes.

PMID- 8290292
TI  - The effect of surfactant on eustachian tube function in a gerbil model of otitis
      media with effusion.
AB  - The relationship of eustachian tube surfactant and otitis media with effusion on
      eustachian tube opening pressure was studied in a gerbil model. Injection of
      killed Streptococcus pneumoniae bacteria created a serous effusion that increased
      eustachian tube opening pressure. The introduction of exogenous surfactant to
      this system resulted in a dramatic decrease in eustachian tube opening pressure
      in both normal ears and those with effusion. Identifying means to increase
      surfactant in the eustachian tube could be beneficial in reducing persistent
      otitis media with effusion.

PMID- 8290293
TI  - Acute otitis media increases middle ear susceptibility to nasal injection of
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa was injected intranasally into four groups of chinchillas
      to determine if these bacteria can invade the middle ear by way of the eustachian
      tube. One group completed penicillin treatment of bilateral penumococcal otitis
      media (POM), and the second group started penicillin treatment of bilateral POM
      at the time of P. aeruginosa injection. A third group had no POM, but completed a
      course of penicillin treatment before P. aeruginosa injection, and a fourth group
      had no POM and received no penicillin. Middle ear susceptibility to nasally
      injected P. aeruginosa was significantly higher in animals with POM (61%) than in
      animals without POM (32%, p = 0.001). Forced eustachian tube opening pressures
      did not correlate with P. aeruginosa susceptibility. Thus, P. aeruginosa, the
      principle pathogen of chronic suppurative otitis media, can invade the middle ear
      by way of the eustachian tube, and acute otitis media predisposes to middle ear
      infection by P. aeurginosa.

PMID- 8290294
TI  - Aberrant reinnervation of the internal branch of the superior laryngeal nerve
      after total laryngectomy.

PMID- 8290295
TI  - An unusual otolaryngologic manifestation of lightning strike.

PMID- 8290296
TI  - Avascular carotid body tumor.

PMID- 8290297
TI  - Posterior laryngeal cleft.

PMID- 8290298
TI  - Clinical application of otoacoustic emissions: what do we know about factors
      influencing measurement and analysis?
AB  - Three electrophysiologic audiologic procedures-aural immittance measurement,
      auditory brainstem response (ABR), and otoacoustic emissions (OAE)- were first
      described in the 1970's. Immittance measurement and ABR have contributed
      importantly for years to the assessment of auditory function in children and
      adults, whereas OAEs have not yet been incorporated into the everyday audiology
      test battery. In this article, we argue that the transition from OAE measurement
      by hearing scientists in laboratory settings to routine application by
      audiologists in the clinic will be greatly facilitated by (1) comprehensive,
      large-scale studies of the effects of subject characteristics, such as gender and
      age (from infancy to advancing adulthood), on both transient evoked (TEOAE) and
      distortion product (DPOAE) otoacoustic emissions; (2) clinical investigations of
      TEOAE and DPOAE in sizeable patient populations with specific neurotologic
      diagnoses; (3) guidelines for OAE test protocols in clinical environments; and
      (4) clear criteria for OAE analysis in clinical populations.

PMID- 8290299
TI  - The First Jerger Lecture. Contralateral suppression of otoacoustic emissions: an
      index of the function of the medial olivocochlear system.
AB  - We can now distinguish, in part, between nerve deafness and hair cell deafness
      through the use of otoacoustic emissions. We can also assess the efferent system
      by carefully quantifying the effects of contralateral stimulation on these same
      otoacoustic emissions. The suppression of transient evoked emissions by
      continuous contralateral white noise is an ostensibly small effect of 2 or 3 dB
      when studied over a 20-msec window. However, when subjected to microstructural
      analysis, the effect can exceed 6 to 8 dB in the zones from 10 to 20 msec after
      the stimulus has subsided. Temporal and spectral analyses reveal robust effects
      of contralateral lateral stimulation, although in any given normal subject it may
      be difficult to separate middle ear effects from efferent effects. Evidence is
      strong that the efferent effect is mediated in part by cholinergic-primarily
      nicotinic-receptors in the outer hair cell. However, a unique type of patient,
      who shows nearly normal pure-tone audiograms and absent ABRs, shows virtually no
      contralateral suppression of transient evoked emissions. Some other patients,
      with symptoms of Charcot-Marie-Tooth disease, may paradoxically show extremely
      poor audiograms, but perfectly normal evoked emissions along with absent
      contralateral suppression. The ABR, along with middle ear muscle reflexes and
      masking level differences, are all absent in these patients; we therefore think
      they have a disorder that desynchronizes most of their primary auditory nerve
      fibers and thereby disconnects them from any efferent activity or masking
      cancellation. The existence of such an auditory disorder, characterized by severe
      dysfunction in speech comprehension-especially when listening in noise-suggests
      that what appears to be a "central auditory imperception" might stem instead from
      a systemic peripheral primary neuropathy.

PMID- 8290300
TI  - Hearing loss in infants with craniofacial anomalies.
AB  - Results of auditory brainstem response (ABR) evaluation of 145 infants, ages 6
      months and younger with craniofacial anomalies (CFA), were examined to determined
      predicted degree and nature of hearing loss. Approximately 50% of infants
      demonstrated at least mild bilateral hearing loss. Presence and degree of hearing
      loss varied by CFA. All infants with bilateral aural atresia exhibited at least a
      moderate bilateral hearing loss; less than 20% of infants with isolated external
      ear anomalies (ear tags, isolated microtia) exhibited any degree of hearing loss.
      In 92% of infants with hearing loss, results of ABR were consistent with
      primarily conductive dysfunction. Implications for early identification and
      audiologic management of infants with CFA and hearing loss are discussed.

PMID- 8290301
TI  - Sex hormones regulate ABR latency.
AB  - In an effort to characterize more completely the influence of sex hormones on
      auditory brainstem response (ABR) latency, we evaluated the ABRs of normal male
      and female subjects and women with previously diagnosed endocrinologic syndromes.
      We describe ABR latency results from the following subjects: five normal males,
      nine normally cycling females on no hormonal therapy, nine females using oral
      contraceptive pills, five females with premature ovarian failure (POF) undergoing
      cyclic estrogen-progesterone replacement therapy, and five hyperandrogenized
      females with polycystic ovarian disease (PCOD) treated with the gonadotropin
      releasing hormone agonist, Lupron depot, to suppress ovarian steroid production.
      All subjects were between 23 and 40 years of age. Serum levels of estradiol,
      progesterone, testosterone, prolactic, and gonadotropins (lutienizing hormone and
      follicle stimulating hormone) were measured to document the hormonal status of
      each of the subjects at the time of the ABR evaluation. Normal cycling females
      and females with POF underwent ABR testing during different phases of the same
      cycle. Male subjects and females using birth control pills were studied four
      times in the same month at 1-week intervals. Females with PCOD were also studied
      four times; baseline and then at 2-week intervals after the initiation of Lupron
      depot therapy. Increased ABR wave V peak latencies were found to be associated
      with elevated levels of estrogen or testosterone. We have previously reported a
      lengthening of ABR wave V peak latencies coincident with peak estrogen levels
      during the female cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290302
TI  - Auditory P300 abnormalities and leukocyte activation in HIV infection.
AB  - To evaluate whether P300 testing might serve as a screening modality for the
      early detection of HIV-related neuropathology, we tested 26 HIV-infected men (23
      without neurologic symptoms, 2 with peripheral neuropathy, 1 with AIDS-associated
      dementia) and 15 controls. Although they had no overt neurologic symptoms, the
      P300 latency was delayed or undetectable in 30% of patients without clinically
      evident neurologic disease. P300 latencies did not correlate with peripheral
      blood CD4 T-cell count, serum quinolinic acid or p24 antigen levels, or the
      numbers of activated peripheral blood monocytes. Three individuals with abnormal
      P300 latencies had been HIV-seropositive for < or = 1 year, suggesting that
      delayed evoked responses detect early neurologic dysfunction. P300 responses do
      not predict imminent dementia. In only one previously asymptomatic individual
      with abnormal P300 waveforms have overt neurologic symptoms developed during a 2
      year followup. Extended longitudinal studies will be necessary to define the
      predictive value of P300 latencies in the development of AIDS-related dementia.
      However, the sensitivity, quantitative nature, and speed of administration of
      this test suggest that it may be useful for identification of early neurologic
      involvement in HIV infection.

PMID- 8290303
TI  - Variations in maximum amplitude of facial expressions between and within normal
      subjects.
AB  - Definitive proof of efficacy of preventions and therapeutic interventions, and of
      risk factors in lower motor neuron facial paralyses continue to be confounded by
      the lack of repeatable quantitative measures of outcome. Clinical and research
      experience with human facial expression repeatedly demonstrates wide variations
      between subjects. To our knowledge, little information is available to isolate
      and describe the differences in dynamic facial expression between and within
      normal subjects. The purpose of this study is to use a statistical model to
      analyze the components of the observed variations of maximum amplitude
      measurement of image change during normal human subject facial expressions.
      Seventeen consecutive normal adult human subjects with no current or past
      evidence of facial nerve or ear disease were studied. Videotapes of command
      facial expressions were taken using specific and standardized conditions. The
      tapes were analyzed using a new computer-assisted image-change analysis program
      capable of generating dimensional data for the maximum amplitude of expression.
      These data were statistically analyzed using a General Linear Model with Nested
      variables to isolate and define component variations and errors. The General
      Linear Model predicted 88% of the observed total variation (p < 0.05).* A model
      performance this high suggests that most of the important independent variables
      were being studied. The major component of the variations was the difference
      among (between) subjects. Seventy-seven percent of the predicted variation was
      due to this difference (p < 0.05). Little of the variation (1%) seemed to be
      within-subjects. Test-retest agreement was acceptable.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8290304
TI  - Effects of probe insertion depth on real ear measurements.
AB  - The purpose of this article is to provide an overall summary of the role probe
      insertion depth has on real ear measurements, and to compare the real ear sound
      pressure level measured by a probe microphone system, using three methods for
      positioning the probe in an ear canal. The probe insertion techniques that were
      compared included: (1) an acoustic method that incorporates use of the quarter
      wave antiresonance property of the ear to determine acoustically the location of
      the probe tube relative to the eardrum in an individual ear; (2) a constant
      insertion depth method (25 mm from the intratragal notch); and (3) the earmold +5
      mm method, which places the probe 5 mm beyond the tip of the individual's earmold
      in the canal, thereby avoiding problems associated with the transition region,
      where sound exits from the bore of the earmold into the larger ear canal.
      Measurements were obtained for each method at 32 frequencies in the unoccluded
      ears of 17 subjects. Results indicated that the sound pressure levels measured by
      the acoustic method were significantly larger than those measured by the other
      two methods. This result was most evident in subjects with long ear canals (> 25
      mm) and at high test frequencies (4.0 to 6.3 kHz). For subjects with short or
      average length ear canals, the three methods provided essentially equivalent
      results.

PMID- 8290305
TI  - A Revised Speech Intelligibility Rating (RSIR) test: listeners with normal
      hearing.
AB  - Two experiments were conducted to examine the intelligibility of 72 passages of
      connected discourse prepared by Cox and McDaniel in their development of the
      Speech Intelligibility Rating (SIR) test. Intelligibility was assessed with a
      method-of-adjustment (MOA) procedure in which listeners adjusted the level of a
      multi-talker babble until they could just understand 50% of a passage; the
      measure of intelligibility was the signal-to-babble ratio, dB S/B. The objective
      was to develop a Revised Speech Intelligibility Rating (RSIR) test that would
      comprise a large number of equivalent passages that produce reliable
      intelligibility measures. In experiment 1, the S/B ratio was based on the overall
      root-mean-square (rms) levels of speech and babble, as represented by the average
      level of frequent peaks observed on a VU meter. Across all 72 passages, mean
      intelligibility was -1.43 dB S/B, and the measure of intelligibility for 42
      passages was within +/- 0.5 dB of the overall mean for all 72 passages. In
      experiment 2, the S/B ratio was based on long-term rms levels of speech and
      babble measured in 16 one-third-octave bands, with center frequencies from 160 to
      5000 Hz. In an effort to achieve greater equivalence in intelligibility among
      passages, the overall rms level of each passage was attenuated by the difference
      between SB16-band for an individual passage and S/B16-band for a reference
      passage. Mean intelligibility across all 72 passages was -8.06 dB, and the
      measure of intelligibility was within +/- 0.5 dB of the overall mean for 64 of
      the 72 passages. For those 64 passages, the 95% critical difference for five MOAs
      was 0.72 dB, which corresponds to an estimated percentage critical difference of
      10.8%.

PMID- 8290306
TI  - The brain stem evoked response and medial nucleus of the trapezoid body.
AB  - Single-unit responses of cat superior olivary complex neurons to acoustic stimuli
      were examined to determine whether the units' action potentials were sufficiently
      synchronized to contribute to the brain stem evoked response. The medial nucleus
      of the trapezoid body and lateral superior olive are two major nuclei within the
      cat superior olivary complex. The first-spike discharge latencies of medial
      nucleus of the trapezoid body and lateral superior olivary neurons to monaural
      presentations of tone burst stimuli were measured as a function of stimulus
      level. Evidence is provided to support the hypotheses that in cat the medial
      nucleus of the trapezoid body may contribute directly to the monaural brain stem
      evoked response by producing action potentials synchronized to stimulus onset and
      may also contribute indirectly to the brain stem evoked response binaural
      difference wave bc by inhibiting the lateral superior olive unit excitatory
      responses synchronized to stimulus onset.

PMID- 8290308
TI  - [General principles of the production and use of retroviral vectors].
AB  - This paper describes the various strategies for somatic gene therapy. There are
      two main scenarios: the ex vivo approach and the in vivo approach. As recombinant
      retroviruses were used in the first clinical trials of gene therapy, their main
      characteristics (structure, efficient production of helper-free viral stocks by
      using packaging cells, transduction procedures) are discussed as well as the
      related safety issues. Finally, retroviral vectors can also be used as a new tool
      to investigate various clinical situations as they allow to mark cells by stably
      integrating in the cellular genome.

PMID- 8290307
TI  - Serotonin and serotonin receptors in the central auditory system.
AB  - Immunohistochemical and ligand-binding techniques were used to visualize the
      neurotransmitter serotonin and one of its receptors, the 5-HT1A subtype, in
      auditory nuclei of the brainstem. Serotonergic fibers and terminal endings were
      found in all auditory nuclei extending from the cochlear nucleus to the inferior
      colliculus, including the superior olivary complex and the nuclei of the lateral
      lemniscus. The density of the innervation varied between and within each nucleus.
      All serotonergic cell bodies were located outside the auditory nuclei. The 5-HT1A
      receptor subtype was found in the cochlear nucleus as well as in the inferior
      colliculus. With no serotonergic cell bodies present in the auditory nuclei, the
      present neuroanatomic and neurochemical findings support behavioral and
      neurophysiologic findings that the serotonergic system may modulate central
      auditory processing.

PMID- 8290309
TI  - [Values and limits of adenoviral vectors for gene transfer in vivo].
AB  - Review of the therapeutic use of DNA transfer to treat a certain number of
      hereditary diseases (such as adenosine deaminase deficiency) or acquired
      diseases. The strategies (ex vivo manipulation or direct in vivo transfer of the
      corrective gene), vectors (retrovirus, adenovirus, nonviral vectors), and
      diseases which can benefit from gene therapy are considered and discussed
      together with an evaluation of the risk of gene therapy.

PMID- 8290310
TI  - Strategies for gene therapy.
AB  - The use of retroviral-mediated gene transfer to introduce a DNA label into T
      cells (TIL) being used in the immunotherapy of patients with malignant melanoma
      finally opened the door to the clinical application of gene therapy for a wide
      variety of inherited and acquired diseases. The gene therapy trial for ADA
      deficiency SCID has demonstrated that long term stable expression of exogenous
      genes can be achieved in human T lymphocytes using retroviral vectors for ex vivo
      treatment and that significant immune reconstitution can be achieved in these
      patients following periodic infusions with ADA gene-corrected autologous T cells.
      Newer clinical applications include the insertion of genes into CD34 enriched
      stem cell populations, the testing of autologous tumor vaccines employing
      cytokine gene-modified tumor cells and the direct transfer of the herpes
      thymidine kinase gene into brain tumors in situ in order to render those tumors
      sensitive to treatment with the ordinarily non-cytotoxic drug ganciclovir.

PMID- 8290311
TI  - Gene therapy for pulmonary diseases.
AB  - The common fatal hereditary disorders, alpha 1-antitrypsin (alpha 1AT) deficiency
      and cystic fibrosis (CF), are clinical models for the common lung diseases,
      emphysema and chronic bronchitis, respectively. Both are potentially amenable to
      therapeutic intervention by gene therapy, in which the relevant gene is used to
      modify cells of the affected individual. Although the gene therapy strategies for
      these diseases are conceptually quite different, a promising approach for both is
      the in vivo administration of a recombinant replication deficient adenovirus
      vector containing a normal copy of the abnormal gene. If the goal is to express
      the normal extracellular anti-protease alpha 1 AT, the route of administration
      could be directly into the lung, liver or vascular endothelium. If the goal is to
      express the normal transmembrane protein defective in CF epithelial cells, the
      new gene will need to be delivered directly to the affected cells. The
      feasibility of these approaches has been demonstrated in vitro and in vivo in
      experimental animals.

PMID- 8290312
TI  - [Cellular therapy and gene therapy: perspectives in neuromuscular pathology].
AB  - Identification of the gene coding for the protein (dystrophin) which is lacking
      or abnormal in Duchenne or Becker type human muscular dystrophies was a decisive
      turning point in neuro-muscular pathology. Since that time, a considerable number
      of gene abnormalities have been identified or at least localized. The severity of
      these diseases, their steady evolution and the absence of any efficient drug
      therapy, have lead to the development of new therapeutic approaches based on
      restoring the genetic capacities of the muscle cell. There are two possibilities
      for therapy. The first is based on the transfer of myogenic cells derived from
      the 'satellite' cells normally present at the periphery of muscle fibers. The
      results obtained from a murine model of Duchenne dystrophy ('mdx' mouse) were
      very promising. However, the results from application of the same techniques to
      the canine model (GRMDX) or to affected children are, at the present time,
      disappointing. A number of biological questions remain to be solved before this
      technique can be more extensively applied to humans. The second possibility is
      based on gene transfer, through a viral vector. The adenovirus is presently a
      possible vector. The first experimental results, on 'mdx' mice, are again very
      encouraging. Extension of these studies to the canine model is a necessary
      prerequisite for any human application. It should be noted that these two
      approaches are complementary. Their future applications may depend on the diffuse
      or selective nature of the skeletal muscle atrophy, and on whether cardiac and
      respiratory muscles are involved.

PMID- 8290313
TI  - [Gene therapy and cancer: from concepts to clinical applications].
AB  - The cure of human cancers at a micro- or macro-metastatic stage of the disease is
      restricted to chemocurable forms which represent only 10% of all leukemias,
      lymphomas and solid tumors. Local conditions in the tumor site and biological
      characteristics of tumor cells are responsible for the resistance to treatment of
      many malignant tumors. Gene therapy can be applied to locally incurable tumors as
      well as to systemically disseminated malignancies. Genic "Surgery" can be
      produced by local intra- or peritumoral injection of viral vectors and/or virus
      producing cells. For example in the case of brain tumors the use of retroviruses
      which are cell-cycle dependent for the injection of target cells is expected to
      spare the non-cycling normal brain cells from the dividing tumor cells. Three
      main types of systemic gene therapy are presently under study: a) VDEPT (Virally
      Directed Enzyme Prodrug Therapy) attempts to induce the production of an enzyme
      which transforms a prodrug into a cytotoxic drug in the engineered tumor cells.
      b) Ecotropic genic immunotherapy (tumor-site directed immunotherapy) can be used
      to produce sufficient local concentrations of cytokines to induce antitumor
      immune response at the tumor site(s). c) Systemic antigenic gene therapy aims to
      induce tumor-specific antigens by transfection of tumor cells in order to
      initiate immune rejection of residual disease by the patient lymphocytic killer
      cells. The conceptual basis and the limitations of these therapeutic approaches
      are discussed.

PMID- 8290314
TI  - [Gene therapy and hospital strategy].
AB  - Gene therapy raises strong interrogations among hospital managers. Actually,
      hospital environment is disturbed and moving as well in a legislative political
      and statutory level as in an economical (competition, consumerism, proximity of
      the establishments) and demographic one (ageing, new pathologies). The fast
      development of medical technologies amplifies this disturbance. In front of that
      environment, the hospital has to anticipate the arriving of gene therapy without
      underestimating the deontological, medical, economical and judicial risks. The
      decisions of implantation have to be taken in a collective way, and seriously
      planned and estimated on a medical and economical level. The way to train people
      and to forecast their careers don't have to be underestimated in consideration of
      the challenge which is represented by the gene therapy.

PMID- 8290315
TI  - [Parent imprinting: methylation-epigenetic heredity].

PMID- 8290316
TI  - [Role of the cytoskeleton in the morphogenesis of the apical field of intestinal
      epithelial cells].

PMID- 8290317
TI  - [Epidemiological pattern of the resistance of 153 Salmonella strains (S. typhi
      excluded) isolated in a Tunisian pediatric unit from 1985 to 1990].
AB  - Since 1985 to 1990, 153 isolates of non typhoidic Salmonella were recovered from
      pediatric unit of the Charles Nicolle Hospital in Tunis. The epidemiological
      profile of these isolates was established according to the biochemical and
      serological characterizations, the antibiotic susceptibility patterns (disk
      diffusion method) to betalactams and aminoglycosides. 127 isolates of Salmonella
      spp were from stools and 22 from blood cultures. The main serotypes were S. ser.
      Wien (108 isolates) and S. ser. Typhimurium (21). A sample of 50 isolates was
      selected among the different resistance phenotypes for determination of MICs and
      betalactamase identification by isolelectro-focusing (36 isolates). All of them
      were resistant to ampicillin and carbenicillin but variable for cephaloridine.
      Since 1986 appeared the resistance to cefotaxime and in 1990 all the S. ser. Wien
      isolates were resistant to the 4 betalactams tested including cefotaxime
      associated to streptomycin, kanamycin, gentamicin, tobramycin and amikacin. All
      of them had a high level of resistance to amoxicillin and gentamicin (mean MICs >
      2048 and > 512 mg/l). The mean MIC of cefotaxime was 43.2 mg/l for S. ser. Wien,
      64mg/l for S. ser. Typhimurium and decreased to 1.9 and 0.12 mg/l in combination
      with 1 mg/l of clavulanic acid. The beta-lactam resistance was mediated to
      enzymatic mechanism, at first the betalactamase of TEM-1 type alone, then
      associated to extended-spectrum betalactamase, mainly type SHV-2 since 1986, and
      other new types in 1990. They were under the control of plasmids with different
      sizes.

PMID- 8290318
TI  - Non radioactive single-strand conformation polymorphism (SSCP) analysis of exon
      11 of the CFTR gene using the Pharmacia PhastSystem.
AB  - The authors report here the use of the PhastSystem (Pharmacia) to perform the
      single strand conformation polymorphism analysis of polymerase chain reaction
      products of the exon 11 of the CFTR gene. It provides a rapid (2 hours) safe and
      reliable technique for the development of carrier testing for individuals or
      couples with a family history of cystic fibrosis.

PMID- 8290320
TI  - A pediatrician's view. Pediatric endoscopic surgeons: new kids on the block.

PMID- 8290319
TI  - [Cytomegalovirus infection after transplantation. Virological diagnosis,
      antiviral treatment].
AB  - Cytomegalovirus (CMV) is an important cause of morbidity in organ transplant
      recipients with two major clinical effects: allograft rejection and pneumonitis.
      The issue of effective therapy has increased the need for accurate and rapid
      laboratory methods for diagnosis of viral infections. ELISA, as the most
      serological sensitive tests, are useful for the identification of active CMV
      infection, and the serological response can be sometimes detected before viral
      excretion. There are several commercial reagents for the detection of IgG or IgM
      CMV antibody, and a great variability in terms of sensibility and specificity.
      Because of the slow process of isolating CMV in cell cultures, immediate-early
      antigen detection in infected cells within one or two days of culture, increases
      twice the sensitivity of viral isolation for leukocyte or bronchoalveolar (BAL)
      specimens. Differences in sensitivity of the direct detection of CMV antigen in
      BAL specimens has been reported. Direct detection of CMV antigen in leukocytes is
      particularly important because CMV viremia is considered to be predictive of
      significant CMV disease. CMV antigen detection within leucocytes, by
      immunofluorescence with the aid of monoclonal antibodies to CMV phosphoprotein PP
      65, appears to be as specific, more sensitive, and allows a more rapid diagnosis
      than virus isolation techniques. Some specific CMV probes are now available, but
      the hybridization techniques involving dot-blot assays of urine or BAL are not
      enough sensitive to detect small amounts of virus. Closely sensitivity to
      isolation in culture has nevertheless been reported in the polymorphonuclear
      fraction of the blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290321
TI  - Laparoscopic cholecystectomy.

PMID- 8290322
TI  - Laparoscopic appendectomy.
AB  - Laparoscopy offers the surgeon better visibility for performing an appendectomy,
      which is to the advantage of the child. When the appendix is normal, the
      offending etiology usually can be managed through the same cannulas. With proper
      judgment and training, the laparoscopic technique can be used on almost any
      patient suspected of appendicitis. The ease of the technique, coupled with the
      decreased postoperative morbidity and shorter hospitalization, make the
      laparoscopic operation an important addition to the surgical armamentarium for
      managing acute appendicitis.

PMID- 8290323
TI  - Laparoscopic splenectomy.
AB  - Splenectomy is easily amenable to laparoscopic technique. Compared with the open
      technique, its advantages include improved exposure, decreased pain, improved
      pulmonary function, shortened hospitalization, rapid return to unrestricted
      activities, and improved cosmetic appearance. These advantages are at the expense
      of prolonged operative time that, with experience and improved instruments,
      should diminish.

PMID- 8290324
TI  - Laparoscopic gastrostomy and fundoplication.
AB  - Laparoscopic gastrostomy and fundoplication are a useful alternative to open
      fundoplication and gastrostomy in pediatric patients. Laparoscopic fundoplication
      appears to decrease the length of hospital stay and allow a more rapid recovery.

PMID- 8290325
TI  - Thoracoscopy.

PMID- 8290326
TI  - Perceptual organization of auditory temporal patterns in European starlings
      (Sturnus vulgaris).
AB  - The perception of continuously repeating auditory patterns by European starlings
      was explored in seven experiments. In Experiment 1, 4 starlings learned to
      discriminate between two continuously repeating, eight-element, auditory
      patterns. Each eight-element pattern was constructed from different temporal
      organizations of two elements differing in timbre. In Experiments 2-7, the
      repeating patterns were transformed in ways designed to identify the starlings'
      perceptual organization of the patterns. In Experiment 2, the starlings
      identified patterns beginning with novel starting points. In Experiment 3,
      discrimination performance was adversely affected by reorganizing the elements in
      the patterns. In Experiments 4 and 5, the pattern elements were altered. In
      Experiment 4, the patterns were constructed from two novel elements. In
      Experiment 5, the temporal location of the two pattern elements was reversed. The
      transformations of the patterns in Experiments 4 and 5 affected discrimination
      performance for some, but not all, of the starlings. In Experiments 6 and 7,
      replacing either of the two elements with silent intervals had no effect on
      discrimination performance. The results of these experiments identify basic
      grouping principles that starlings use when they perceive auditory patterns.

PMID- 8290327
TI  - Size contrast as a function of conceptual similarity between test and inducers.
AB  - In four experiments, the effect of the semantic relationship between test and
      inducing stimuli on the magnitude of size contrast in an Ebbinghaus-type illusion
      was explored. In Experiments 1 and 2, the greatest illusion was found when test
      and inducing stimuli were identical in shape and differed only in size. Decreased
      size contrast was found when inducing stimuli were drawn from the same category
      as the test stimulus, but were not visually identical. Even less size contrast
      was found when inducing stimuli were from a near conceptual category, with the
      least effect when they were drawn from a completely different category. In
      Experiment 3, it was demonstrated that even if test and inducing stimuli are
      drawn with identical geometric elements, the size contrast illusion is greatly
      reduced if they represent apparently different conceptual categories (through the
      manipulation of orientation and perceptual set). In Experiment 4, any geometric
      or spatial confounds were ruled out. These results suggest that size contrast is
      strongly influenced by the conceptual similarity between test and inducing
      stimuli.

PMID- 8290328
TI  - The influence of spectral composition of complex tones and of musical experience
      on the perceptibility of virtual pitch.
AB  - A matching paradigm was used to evaluate the influence of the spectral
      characteristics number, relative height, and density of harmonics on the
      perceptibility of the missing fundamental. Fifty-eight musicians and 58
      nonmusicians were instructed to adjust mistuned sinusoids to the subjectively
      perceived fundamental pitches of corresponding overtone spectra. Analyses of
      variance were used to compare the average of absolute and relative deviations of
      the tunings from the highest common divisors of the complex tones. The results
      indicate that musical experience is the most influential single factor
      determining the assessment of fundamental pitch. Nevertheless, all spectral
      parameters significantly affect tuning performance. Systematic relative
      deviations (stretching/compression effects) were observed for all considered
      variables. An increase of the optimum subjective distance between an overtone
      spectrum and its corresponding fundamental was characteristic of musicians and
      unambiguous spectra, whereas the compression effect was typical of nonmusicians
      and complex tones containing spectral gaps.

PMID- 8290329
TI  - Illusory conjunctions and the cerebral hemispheres.
AB  - Two visual half-field experiments tested Moscovitch's (1979) proposition that
      cerebral asymmetry does not concern the earliest perceptual stages but only later
      processing. Subjects were briefly shown displays that included one (Experiment 1)
      or two (Experiment 2) types of forms differing in size and which, according to
      previous evidence, might lead to opposite laterality effects. Laterality effects
      were assessed for correct detections and for illusory conjunctions, both in terms
      of raw detection scores and in terms of perceptual discriminability (d' scores).
      In Experiment 1, displays included either rectangles or triangles. In the first
      case, the target was a cross; in the second case, it was a Star of David. A
      hemifield x size interaction was observed both on correct detections and on
      associated discriminability. Yet, no such interaction was obtained for illusory
      conjunctions or for associated d' scores. In Experiment 2, the two types of forms
      were presented simultaneously, with the small ones either inside or outside the
      large ones. No laterality effects were observed. Some implications of these data
      for both hemispheric asymmetry and feature integration issues are discussed. The
      results suggest that early preattentive processes of feature extraction are not
      lateralized, whereas some integrative mechanisms, such as Treisman's (1988) focal
      attention, may operate differently in the two hemispheres.

PMID- 8290330
TI  - Center of mass perception and inertial frames of reference.
AB  - Center of mass perception was investigated by varying the shape, size, and
      orientation of planar objects. Shape was manipulated to investigate symmetries as
      information. The number of reflective symmetry axes, the amount of rotational
      symmetry, and the presence of radial symmetry were varied. Orientation affected
      systematic errors. Judgments tended to undershoot the center of mass. Random
      errors increased with size and decreased with symmetry. Size had no effect on
      random errors for maximally symmetric objects, although orientation did. The
      spatial distributions of judgments were elliptical. Distribution axes were found
      to align with the principle moments of inertia. Major axes tended to align with
      gravity in maximally symmetric objects. A functional and physical account was
      given in terms of the repercussions of error. Overall, judgments were very
      accurate.

PMID- 8290331
TI  - Center of mass perception: perturbation of symmetry.
AB  - Bingham and Muchisky (1993) found that observers were very accurate in
      determining the location of the center of mass in planar objects. Systematic
      errors were affected primarily by object orientation, while random errors varied
      with the amount of symmetry. Radial and axial reflective symmetry affected errors
      in different ways. In the current study, we investigated the different effects of
      axial reflective versus rotational symmetry. All random errors decreased with
      increasing rotational symmetry. Axial reflective symmetry further reduced errors
      in the direction perpendicular to the axis. We replicated the effect on
      systematic error of orientation. However, we also found an effect of the
      perturbation of symmetry that suggested that observers used an approximation to
      symmetry. To investigate this possibility, we constructed a series of objects in
      which axial reflective symmetry was established and then perturbed by varying
      amounts. We found that systematic errors were structured by the underlying
      approximate symmetries, and we discuss the problem of quantifying symmetry.

PMID- 8290332
TI  - Angular induction is modulated by the orientation of the test segment but not its
      length.
AB  - Angular induction is the basic process by which the orientation of line segments
      can affect the perceived orientation of other segments as well as their
      alignment. In this laboratory, we have found that the effect on alignment follows
      approximately linear rules, with the inducing segment having its greatest
      influence when its orientation is near to that of the segment being judged. Other
      laboratories, however, have reported peak effects when the relative angle between
      the two is at 45 degrees, and with the inducing segment being aligned with one of
      the cardinal axes of the observer. It has been said that the length of the test
      segment being judged is a critical factor, but the first experiment of the
      present study shows a similar linear decline of induction strength irrespective
      of test segment length. The second experiment indicates that the orientation of
      the test segment relative to the observer modulates the induction to determine
      the location of peak effects. A two-factor linear model predicts the observed
      pattern of results.

PMID- 8290333
TI  - Smell and taste function in the visually impaired.
AB  - Surprisingly few quantitative studies have addressed the question of whether
      visually impaired individuals evidence, perhaps in compensation for their loss of
      vision, increased acuteness in their other senses. In this experiment we sought
      to determine whether blind subjects outperform sighted subjects on a number of
      basic tests of chemosensory function. Over 50 blind and 75 sighted subjects were
      administered the following olfactory and gustatory tests: the University of
      Pennsylvania Smell Identification Test (UPSIT); a 16-item odor discrimination
      test; and a suprathreshold taste test in which measures of taste-quality
      identification and ratings of the perceived intensity and pleasantness of
      sucrose, citric acid, sodium chloride, and caffeine were obtained. In addition,
      39 blind subjects and 77 sighted subjects were administered a single staircase
      phenyl ethyl alcohol (PEA) odor detection threshold test. Twenty-three of the
      sighted subjects were employed by the Philadelphia Water Department and trained
      to serve on its water quality evaluation panel. The primary findings of the study
      were that (a) the blind subjects did not outperform sighted subjects on any test
      of chemosensory function and (b) the trained subjects significantly outperformed
      the other two groups on the odor detection, odor discrimination, and taste
      identification tests, and nearly outperformed the blind subjects on the UPSIT.
      The citric acid concentrations received larger pleasantness ratings from the
      trained panel members than from the blind subjects, whose ratings did not differ
      significantly from those of the untrained sighted subjects. Overall, the data
      imply that blindness, per se, has little influence on chemosensory function and
      add further support to the notion that specialized training enhances performance
      on a number of chemosensory tasks.

PMID- 8290334
TI  - Relative and absolute duration judgments under prospective and retrospective
      paradigms.
AB  - A dual-process contingency model of short duration judgment is proposed and
      tested. The first process, or P(t), is a timer that uses cognitive capacity to
      keep track of units of time. If capacity is directed toward other tasks, P(t)
      will record fewer units and produce lower time judgments than when capacity is
      not directed toward other tasks. This timing process is most likely to affect
      performance when people know in advance (prospective judgments) that time
      judgments will be required and when absolute, rather than relative, judgments are
      made. The second process, or P(m), which is used for retrospective and relative
      judgments, judges duration on the basis of the number of remembered high priority
      events (HPEs) occurring during the interval. When this process is used, time
      judgments increase with the amount of HPEs that can be retrieved at the moment of
      judgment. Two experiments are reported. Tactual stimuli were presented, and
      nontemporal information processing load (simple or complex stimuli), type of
      judgment (absolute or relative), and judgment paradigm (prospective or
      retrospective) were manipulated. The results obtained support the proposed dual
      process contingency model.

PMID- 8290335
TI  - Foreshortening and the perception of parallel projections.
AB  - Does picture perception follow polar projective geometry? Parallel projection
      drawings, which are not produced by using rules of polar projection, are widely
      regarded as visually acceptable representations of three-dimensional (3-D)
      objects in free viewing. One explanation is that they are perceived by means of a
      system in which there is no foreshortening. If so, edges of a 3-D block in 1:1
      proportions should be denoted by lines in 1:1 proportions on the picture surface.
      However, three experiments suggest that the perception of parallel projections of
      a block involves foreshortening. In Experiment 1, 90 subjects were shown a set of
      parallel projections of a cube, in which each drawing depicted three sides of the
      cube, drawn as a square with obliques--a frontal square with receding edges shown
      by parallel obliques of various lengths. The subjects preferred a drawing with a
      receding side length that was considerably foreshortened in relation to the front
      side. In Experiments 2 and 3, subjects viewed drawings of three blocks that
      differed in the ratios of the lengths of their receding edges to their frontal
      edges (1:1, 1:2, and 1:0.65). In Experiment 2, the subjects were shown square
      with-obliques drawings of the three blocks with receding edges shown by parallel
      obliques of various lengths. Again, the subjects preferred drawings with a
      receding side that was foreshortened. In Experiment 3, the drawings showed two
      sides of a block. The receding dimension was drawn with parallel or converging
      lines. The preferred foreshortening was not a fixed ratio of the dimensions of
      the 3-D blocks. We suggest that square-with-obliques parallel projections showing
      cubes are taken by vision to be approximations to projections using
      foreshortening. We suggest also that as the line showing the receding edge
      elongates, foreshortening becomes less of a factor.

PMID- 8290336
TI  - Influence of visual guidance on braille recognition: low lighting also helps
      touch.
AB  - This study was an attempt to clarify the mechanisms responsible for the benefits
      of visual guidance in tactual braille recognition. Subjects touched +90 degrees
      tilted braille under normal room lighting, or with low lighting, with or without
      visual guidance. Both visual information about finger angle and spatial reference
      information were manipulated with stained glass and light-emitting diodes. The
      provision of visual information about finger angle alone was no help to braille
      recognition, and performance was low. Adding visual spatial reference information
      to vision of finger angle raised performance. However, recognition accuracy was
      also substantially improved by low lighting. The benefits of darkness for haptics
      did not generalize to the reading of upright, two-letter braille words. It was
      proposed that extraneous visual information may distract sighted subjects in
      haptic tasks that require mental rotation of visual images.

PMID- 8290337
TI  - The interdependence of pitch and temporal judgments by absolute pitch possessors.
AB  - The auditory tau and the kappa effects show that there is time-pitch
      interdependence in our perception. Our judgments of pitch separation between two
      tones depend on the temporal interval between them (the auditory tau effect), and
      our judgments of the tones' temporal interval depend on their pitch separation
      (the kappa effect). The mechanisms underlying this interdependence were
      investigated by studying the auditory tau and the kappa effect in three
      experiments. Comparisons were made between results obtained from subjects with
      absolute pitch and those who did not have absolute pitch, and two frequency
      ranges of pure tones (octave and whole-tone conditions) were selected. The
      procedures had been used in previous experiments (Shigeno, 1986), in which the
      auditory tau and the kappa effects were compared in speech and nonspeech stimuli.
      The present results demonstrate that the auditory tau effect does not occur when
      possessors of absolute pitch judge the closeness of stimuli in pitch, except when
      the stimulus continuum consists of tones that do not correspond to musical notes
      in the whole-tone condition. The kappa effect was obtained in the judgment of
      possessors of absolute pitch in both the octave and the whole-tone conditions.
      These findings suggest that the interaction between temporal interval and pitch
      judgment might be explained in terms of the two different memory modes for
      retaining the pitch of tones, and that these effects occur at the precategorical
      level.

PMID- 8290339
TI  - E1 protein of human papillomavirus is a DNA helicase/ATPase.
AB  - Replication of human papillomavirus (HPV) DNA requires the viral proteins E1 and
      E2. Amino acid similarities to SV40 large-T antigen had suggested that E1 is a
      DNA helicase/ATPase involved in initiating viral DNA replication, and this has
      recently been shown for bovine papillomavirus type 1 (BPV-1) E1 protein. However,
      in vitro analysis of HPV E1 has been hampered by the inability to produce
      purified protein using heterologous expression systems. We have succeeded in
      demonstrating ATPase and DNA helicase activities in purified HPV E1, expressed in
      E. coli as a maltose-binding protein fusion (MBP-E1), for the first time. As
      further confirmation that the ATPase and DNA helicase activities are due to E1
      and not contaminating E. coli enzymes, we have shown that a fusion protein
      containing an amino acid change (E1 Pro-479 to Ser), predicted to inactivate ATP
      binding, has impaired activities. We have carried out a structure prediction
      analysis which suggests that E1 may form two domains: a relatively open N
      terminal domain (residues 1-125), and a highly structured C-terminal domain (170
      649), with an intermediate region (125-170) predicted to form an inter-domain
      linker. This is consistent with the proteolytic susceptibility of MBP-E1 at a
      site 15-20 kD from the N-terminus of E1, and the accumulation of a 58 kD C
      terminal fragment of E1. We speculate that the N-terminal domain is involved in
      DNA-binding, while the C-terminal 58 kD may constitute a distinct enzymatic
      domain. HPV E1 is of interest as a therapeutic target and the availability of
      pure enzyme will be invaluable in the search for antiviral compounds.

PMID- 8290338
TI  - Analysis of the RNA-recognition motif and RS and RGG domains: conservation in
      metazoan pre-mRNA splicing factors.
AB  - We present a systematic analysis of sequence motifs found in metazoan protein
      factors involved in constitutive pre-mRNA splicing and in alternative splicing
      regulation. Using profile analysis we constructed a database enriched in protein
      sequences containing one or more presumptive copies of the RNA-recognition motif
      (RRM). We provide an accurate alignment of RRMs and structure-based criteria for
      identifying new RRMs, including many that lack the prototype RNP-1 submotif. We
      present a comprehensive table of 125 sequences containing 252 RRMs, including 22
      previously unreported RRMs in 17 proteins. The presence of a putative RRM in
      these proteins, which are implicated in a variety of cellular processes, strongly
      suggests that their function involves binding to RNA. Unreported homologies in
      the RRM-enriched database to the metazoan SR family of splicing factors are
      described for an Arg-rich human nuclear protein and two yeast proteins (S. pombe
      mei2 and S. cerevisiae Npl3). We have rigorously tested the phylogenetic
      relationships of a large sample of RRMs. This analysis indicates that the RRM is
      an ancient conserved region (ACR) that has diversified by duplication of genes
      and intragenic domains. Statistical analyses and classification of repeated Arg
      Ser (RS) and RGG domains in various protein splicing factors are presented.

PMID- 8290340
TI  - Differential roles for Fos and Jun in DNA-binding: redox-dependent and
      independent functions.
AB  - The Fos and Jun family of transcription factors contain an invariant sequence
      motif lysine-cysteine-arginine (KCR) in the highly conserved DNA-binding region.
      Reduction of the cysteine residue is necessary to facilitate DNA-binding. Here,
      we examined the potential dual roles of the flanking lysine and arginine residues
      in influencing the redox reactivity of the cysteine and the DNA-binding activity
      of Fos and Jun. Two sets of Fos and Jun mutants were generated: the KCR and KSR
      series representing proteins capable of redox-dependent and redox-independent DNA
      binding activity, respectively. Mutation of the lysine in Fos-Jun heterodimers
      had no obvious effect on the redox reactivity of the cysteine, suggesting that
      lysine is not essential in this respect. However, mutation of the arginine but
      not lysine, in both the KCR and the KSR series abolished DNA-binding activity.
      Thus, the arginine but not the lysine residue in the KCR motif is critical for
      both redox-dependent and redox-independent functions in DNA-binding.
      Surprisingly, the triple substitution, ISI, exhibited high levels of DNA-binding
      activity. This demonstrates that the effects of amino acid substitutions can be
      highly dependent on context and that non-basic amino acids can function
      efficiently in DNA-binding. Analysis of combinations of wild-type and mutant Fos
      and Jun proteins indicated that Fos was dominant in dictating the DNA-binding
      ability of Fos-Jun heterodimers. This suggests that the lysine and arginine
      residues in the KCR region of Fos are not equivalent to those in Jun and that
      they interact with DNA differently.

PMID- 8290342
TI  - Differences in the accessibility of methylated and unmethylated DNA to DNase I.
AB  - DNase I binds in the minor groove of DNA and is used as an enzymatic tool to
      investigate the interaction of proteins with DNA. Here we show that the major
      groove located 5-methyldeoxycytidine can enhance or inhibit the cleavage rates of
      DNA by DNase I. This effect may be caused in part by changes in DNA structure
      affecting the accessibility of the minor groove of DNA to DNase I.

PMID- 8290341
TI  - An 'elaborated' pseudoknot is required for high frequency frameshifting during
      translation of HCV 229E polymerase mRNA.
AB  - The RNA polymerase gene (gene 1) of the human coronavirus 229E is approximately
      20 kb in length and is located at the 5' end of the positive-strand genomic RNA.
      The coding sequence of gene 1 is divided into two large open reading frames,
      ORF1a and ORF1b, that overlap by 43 nucleotides. In the region of the ORF1a/ORF1b
      overlap, the genomic RNA displays two elements that are known to mediate (-1)
      ribosomal frameshifting. These are the slippery sequence, UUUAAAC, and a 3'
      pseudoknot structure. By introducing site-specific mutations into synthetic
      mRNAs, we have analysed the predicted structure of the HCV 229E pseudoknot and
      shown that besides the well-known stem structures, S1 and S2, a third stem
      structure, S3, is required for a high frequency of frameshifting. The requirement
      for an S3 stem is independent of the length of loop 2.

PMID- 8290343
TI  - Instability of the monofunctional adducts in cis-[Pt(NH3)2(N7-N-methyl-2
      diazapyrenium)Cl](2+)-modified DNA: rates of cross-linking reactions in cis
      platinum-modified DNA.
AB  - Single- and double-stranded oligonucleotides containing a single monofunctional
      cis-[Pt(NH3)2(dG)(N7-N-methyl-2-diazapyrenium)]3+ adduct have been studied at two
      NaCl concentrations. In 50 mM and 1 M NaCl, the adducts within the single
      stranded oligonucleotides are stable. In contrast, they are unstable within the
      corresponding double-stranded oligonucleotides. In 50 mM NaCl, the bonds between
      platinum and guanine or N-methyl-2,7-diazapyrenium residues are cleaved and
      subsequently, intra- or interstrand cross-links are formed as in the reaction
      between DNA and cis-DDP. In 1 M NaCl, the main reaction is the replacement of N
      methyl-2,7-diazapyrenium residues by chloride which generates double-stranded
      oligonucleotides containing a single monofunctional cis-[Pt(NH3)2(dG)Cl]+ adduct.
      The rates of closure of these monofunctional adducts to bifunctional cross-links
      have been studied in 60 mM NaClO4. Within d(TG.CT/AGCA), d(CG.CT/AGCG) and
      d(AG.CT/AGCT) (the symbol.indicates the location of the adducts in the central
      sequences of oligonucleotides), the half-lifes (t1/2) of the cis
      [Pt(NH3)2(dG)Cl]+ adducts are respectively 12, 6 and 2.8 hr and the cross-linking
      reactions occur between guanine residues on the opposite strands. Within
      d(AG.TC/GACT), d(CG.AT/ATCG) and d(TGTG./CACA) or d(TG.TG/CACA) t1/2 are
      respectively 1.6, 8 and larger than 20 hr and the intrastrand cross-links are
      formed at the d(AG), d(GA) and d(GTG) sites, respectively. The conclusion is that
      the rates of conversion of cis-platinum-DNA monofunctional adducts to minor
      bifunctional cross-links are dependent on base sequence. The potential use of the
      instability of cis-[Pt(NH3)2(dG)(N7-N-methyl-2-diazapyrenium)]3+ adducts is
      discussed in the context of the antisense strategy.

PMID- 8290344
TI  - Point mutations 5' to the tRNA selenocysteine TATA box alter RNA polymerase III
      transcription by affecting the binding of TBP.
AB  - The selenocysteine tRNA(Sec) gene possesses two external promoter elements, one
      of which is constituted by a strong TATA box. Point mutant analysis performed in
      this study led to the conclusion that the functional TATA promoter actually
      encompasses the sequence -34 GGGTATAAAAGG-23. Individual changes at T-31 do not
      affect transcription much. Position T-29 is less permissive to mutation since
      transversion to a G, for example, is less well tolerated than at T-31.
      Interestingly, a double point mutation, converting GG(-33/-32) to TT, causes
      abrogation of transcription in vivo and severe reduction of transcription in
      vitro with human TBP. Therefore, data obtained underscore the fact that, in the
      Xenopus tRNA(Sec), these two Gs are an integral part of the TATA promoter. Gel
      retardation experiments indicate that the GG to TT substitution, which led human
      TBP to lose its ability to support efficient transcription in vitro, correlates
      with the appearance of an altered pattern of retarded complexes. Altogether, the
      data presented in this report support a model in which TBP interacts directly
      with the TATA element of the tRNA(Sec) gene, in contrast to the type of
      interaction proposed for classical TATA-less tRNA genes.

PMID- 8290345
TI  - Proton NMR studies of manganese ion binding to tRNA-derived acceptor arm
      duplexes.
AB  - Several RNA duplexes corresponding to the acceptor arms of different tRNAs have
      been analyzed with respect to their divalent metal ion binding capability by
      means of proton NMR spectroscopy using paramagnetic Mn2+ ions as probes. In
      particular, the role of GU wobble base pairs has been analyzed with reference to
      their potential for creating metal ion binding sites. It is shown that both the
      structural modifications induced by GU pairs in the A-RNA geometry and the
      sequence context seem to affect the metal ion binding capabilities.

PMID- 8290346
TI  - The organisation of repetitive sequences in the pericentromeric region of human
      chromosome 10.
AB  - Three satellite DNA families are present in the pericentromeric region of
      chromosome 10; the alpha satellite and two 5 bp satellite families defined here
      as satellites 2 and 3. Pulsed field gel electrophoresis (PFGE) demonstrates that
      these sequences are organised into five discrete arrays which are linked within a
      region of approximately 5.3 Megabases (Mb) of DNA. The alpha satellite is largely
      confined to a 2.2 Mb array which is flanked on its p arm side by two 100-150 kb
      satellite 3 arrays and on its q arm side by a 900 kb satellite 2 array and a
      further 320 kb satellite 3 array. This linear order is corroborated by
      fluorescent in situ hybridisation analyses. In total, these arrays account for
      3.6 Mb of DNA in the pericentromeric region of chromosome 10. These data provide
      both physical information on sequences which may be involved in centromere
      function and a map across the centromere which has the potential to link yeast
      artificial chromosome (YAC) contigs currently being developed on both arms of
      this chromosome.

PMID- 8290347
TI  - Transcription of a silkworm tRNA(cAla) gene is directed by two AT-rich upstream
      sequence elements.
AB  - A region within 35 nucleotides upstream of the transcription initiation site of a
      variety of silkworm Class III templates is absolutely required for transcription
      in vitro. To determine whether the activity of this region can be attributed to a
      particular sequence element, we systematically replaced 4-5 bp segments of the
      region upstream of a silkworm tRNA(cAla) gene. We show that replacement of either
      of two AT-rich blocks markedly impairs promoter function, whereas replacement of
      other sequences has little or no effect. Additional mutants were constructed to
      test whether base composition or sequence is important for function of the AT
      blocks. We find that some sequences are more effective than others, but that
      various AT-rich sequences can direct transcription at a high level. Possible
      mechanisms by which such elements could act are discussed.

PMID- 8290348
TI  - An indirect negative autoregulatory mechanism involved in hepatocyte nuclear
      factor-1 gene expression.
AB  - Recent studies have revealed that hepatocyte nuclear factor 4 (HNF-4) is an
      essential positive regulator of another liver enriched transcription factor HNF
      1, defining a transcriptional hierarchy between the two factors operating in
      hepatocytes. To assess the possible autoregulation of the HNF-1 gene we have
      examined the effect of HNF-1 on its own transcription. In transient transfection
      assays, HNF-1 strongly down-regulated transcription driven by its own promoter in
      HepG2 cells. In addition HNF-1 also repressed the activity of HNF-4 dependent
      ApoCIII and ApoAI promoters. The same effect was observed using vHNF-1, a
      distinct but highly related protein to HNF-1. Both HNF-1 and vHNF-1 downregulated
      HNF-4 activated transcription from intact and chimeric promoter constructs
      carrying various HNF-4 binding sites implying that they act by impeding HNF-4
      binding or activity. DNA binding and cell free transcription experiments however
      failed to demonstrate any direct or indirect interaction of HNF-1 and vHNF-1 with
      the above regulatory regions. Both factors repressed HNF-4 induced transcription
      of the ApoCIII and HNF-1 genes in HeLa cells, arguing against the requirement of
      a hepatocyte specific function. These findings define an indirect negative
      autoregulatory mechanism involved in HNF-1 gene expression, which in turn may
      affect HNF-4 dependent transcription of other liver specific genes.

PMID- 8290349
TI  - Deficient repair of the transcribed strand of active genes in Cockayne's syndrome
      cells.
AB  - Removal of ultraviolet light induced cyclobutane pyrimidine dimers (CPD) from
      active and inactive genes was analyzed in cells derived from patients suffering
      from the hereditary disease Cockayne's syndrome (CS) using strand specific
      probes. The results indicate that the defect in CS cells affects two levels of
      repair of lesions in active genes. Firstly, CS cells are deficient in selective
      repair of the transcribed strand of active genes. In these cells the rate and
      efficiency of repair of CPD are equal for the transcribed and the nontranscribed
      strand of the active ADA and DHFR genes. In normal cells on the other hand, the
      transcribed strand of these genes is repaired faster than the nontranscribed
      strand. However, the nontranscribed strand is still repaired more efficiently
      than the inactive 754 gene and the gene coding for coagulation factor IX.
      Secondly, the repair level of active genes in CS cells exceeds that of inactive
      loci but is slower than the nontranscribed strand of active genes in normal
      cells. Our results support the model that CS cells lack a factor which is
      involved in targeting repair enzymes specifically towards DNA damage located in
      (potentially) active DNA.

PMID- 8290350
TI  - Identification of DNA--cisplatin adducts in a blind trial of in situ scanning
      tunneling microscopy.
AB  - Scanning tunneling microscopy (STM) reveals nanometer scale details of hydrated
      DNA but the interpretation of the images is controversial because of substrate
      artifacts and the lack of a theory for image contrast. We demonstrate that we
      have overcome these problems by identifying five DNA samples by their STM images
      alone in a blinded trial. The samples were single-stranded and double-stranded
      DNA with and without covalent modification by the anti-tumor drug cisplatin. The
      cisplatin adducts were distinguished by substantial kinking at the drug binding
      site. The oligomers were 20 bases in length, which was too short to permit the
      kinking angle to be determined with precision. However, models with a 45 degree
      kink gave a better fit to the images of the duplex adducts than models with a 90
      degrees kink. A variety of structures was observed for the single-stranded
      adducts.

PMID- 8290351
TI  - Stimulation of gene expression by introns: conversion of an inhibitory intron to
      a stimulatory intron by alteration of the splice donor sequence.
AB  - Efficient expression of many mammalian genes depends on the presence of at least
      one intron. We previously showed that addition of almost any of the introns from
      the mouse thymidylate synthase (TS) gene to an intronless TS minigene led to a
      large increase in expression. However, addition of intron 4 led to a reduction in
      minigene expression. The goal of the present study was to determine why TS intron
      4 was unable to stimulate expression. Insertion of intron 4 into an intron
      dependent derivative of the ribosomal protein L32 gene did not lead to a
      significant increase in expression, suggesting that its inability to stimulate
      expression was due to sequences within the intron. Deleting most of the interior
      of intron 4, improving the putative branch point, removing purines from the
      pyrimidine stretch at the 3' end of the intron, or removing possible alternative
      splice acceptor or donor sites within the intron each had little effect on the
      level of expression. However, when the splice donor sequence of intron 4 was
      modified so that it was perfectly complementary to U1 snRNA, the modified intron
      4 stimulated expression approximately 6-fold. When the splice donor site of TS
      intron 1 (a stimulatory intron) was changed to that of TS intron 4, the modified
      intron 1 was spliced very inefficiently and lost the ability to stimulate mRNA
      production. Our observations support the idea that introns can stimulate gene
      expression by a process that depends directly on the splicing reaction.

PMID- 8290352
TI  - Modulation of oligonucleotide duplex and triplex stability via hydrophobic
      interactions.
AB  - Synthetic oligonucleotides have been proposed as a new rationally designed class
      of pharmaceuticals with a mechanism of action based upon a Watson-Crick and/or
      Hoogsteen type of base pairing with RNA or DNA regions of interest. Two series of
      3'-cholesterol and/or 5'-cholesterol conjugated oligonucleotides have been
      synthesized. The primary structure of these compounds was conceived in a way that
      should allow a hydrophobic interaction to take place upon bringing the
      cholesteryl moieties into proximity via a hybridization event. In the first group
      of compounds the cholesteryl group was tethered to the opposite ends of two
      oligonucleotides, tandemly addressed to the same complementary strand. An
      increase in the Tm of duplexes up to 13.3 degrees C was observed in comparison to
      unmodified oligomers. We observed a higher level of mismatch discrimination for
      the two contiguous oligonucleotide cholesterol conjugates compared to one
      continuous oligomer of the same length. A second group of compounds was
      synthesized as 5',3'-bis-cholesterol containing oligomers, capable of forming
      'clamp-shaped' triple-stranded complexes, where cholesterol groups were attached
      to the termini of duplex and triplex forming domains. Stabilization of triplexes
      by up to 30 degrees C due to inter-cholesteryl interaction was observed. We
      detected no triplex formation with a mismatched target. These data suggest that
      significant stabilization of complexes of nucleic acids could be achieved through
      inter-cholesteryl hydrophobic interaction.

PMID- 8290353
TI  - Mouse Brn-3 family of POU transcription factors: a new aminoterminal domain is
      crucial for the oncogenic activity of Brn-3a.
AB  - The class IV POU domain genes Brn-3a, -b and -c are differentially expressed
      during neural development and at least Brn-3a also in neuroectodermal tumors. In
      contrast to Brn-3b and Brn-3c, Brn-3a encodes two protein variants: Brn-3a(l) and
      Brn-3a(s). Brn-3a(s) lacks 84 aminoterminal residues but is otherwise identical
      to Brn-3a(l). Outside the well conserved carboxyterminal POU domains all three
      Brn-3 proteins (-a, -b and -c) diverge until the aminoterminal end where a new
      domain of about 100 amino acids is identified. This domain is conserved only
      between Brn-3 proteins and other class IV POU factors. Brn-3a(l) that contains
      the complete domain but not Brn-3a(s) that lacks 84 amino acids of it is able to
      tumorigenically transform primary fibroblasts. Brn-3b that lacks 40 amino acids
      of the new domain does itself not transform, but abolishes the oncogenic
      potential of Brn-3a(l) when transfected together. This demonstrates not only that
      Brn3-a(l) is a proto-oncogene and may well be causally involved in the generation
      of neuroectodermal tumors but also suggests that the intactness of the new
      aminoterminal domain described here is crucial for oncogenic activity. In
      addition, our data indicate that Brn-3b acts as an inhibitor of Brn-3a(l)
      activity.

PMID- 8290354
TI  - RAPD (arbitrary primer) PCR is more sensitive than multilocus enzyme
      electrophoresis for distinguishing related bacterial strains.
AB  - The RAPD (random amplified polymorphic DNA) fingerprinting method, which utilizes
      low stringency PCR amplification with single primers of arbitrary sequence to
      generate strain-specific arrays of anonymous DNA fragments, was calibrated
      relative to the widely used, protein-based multilocus enzyme electrophoretic
      (MLEE) typing method. RAPD fingerprinting was carried out on five isolates from
      each of 15 major groups of Escherichia coli strains that cause diarrheal disease
      worldwide (75 isolates in all). Each group consisted of isolates that were not
      distinguishable from one another by MLEE typing using 20 diagnostic enzyme
      markers. In our RAPD tests, three or more distinct subgroups in each MLEE group
      were distinguished with each of five primers, and 74 of the 75 isolates were
      distinguished when data obtained with five primers were combined. Thus, RAPD
      typing is far more sensitive than MLEE typing for discriminating among related
      strains of a species. Despite their different sensitivities, the same general
      relationships among strains were inferred from MLEE and RAPD data. Thus, our
      results recommend use of the RAPD method for studies of bacterial population
      genetic structure and evolution, as well as for epidemiology.

PMID- 8290355
TI  - Bacteriophage T4 and human type I DNA ligases relax DNA under joining conditions.
AB  - Both bacteriophage T4 and human type I DNA ligases in the presence of a mixture
      of ATP, AMP and PPi altered the topological properties of a supercoiled substrate
      by a step-wise reaction eventually leading to a population of fully relaxed,
      covalently closed products. In the presence of only AMP and PPi DNA products
      containing nicks with 3'OH/5'P termini accumulated in the presence of
      bacteriophage T4 DNA ligase, suggesting reversal of the entire joining reaction,
      but not in the presence of human DNA ligase I. Both DNA ligases became
      deoxyadenylylated in the presence of dATP, but the joining reaction did not
      proceed to completion. However, with both enzymes the full relaxing reaction took
      place in the presence of dAMP alone and in the presence of a mixture of dATP,
      dAMP and PPi. In no case could the joining reaction be reversed by dAMP and PPi.
      Related experiments with modified derivatives of deoxyribonucleoside 5'
      triphosphates and PPi gave results in accord with these observations. The AMP
      dependent DNA relaxation catalysed by DNA ligases was insensitive to the presence
      of exonuclease III. These results indicate that controlled relaxation of the
      substrate by both DNA ligases occurs as a separate reaction rather than by simple
      reversal of the joining reaction. These findings support the hypothesis that in
      vivo the DNA topoisomerising ligases relax their substrate at the replication
      fork both during and separately from ligation of a pre-existing nick.

PMID- 8290356
TI  - The fission yeast rad22 gene, having a function in mating-type switching and
      repair of DNA damages, encodes a protein homolog to Rad52 of Saccharomyces
      cerevisiae.
AB  - The gene rad22 of the fission yeast Schizosaccharomyces pombe has a function in
      DNA repair and mating-type switching. We have cloned the rad22 gene from a
      genomic gene bank by functional complementation of the switching defect. An open
      reading frame coding for a putative protein of 469 amino acids was found by
      sequence analyses. The rad22 gene contains no intron. A region of 126 amino acids
      in the N-terminal half of the Rad22 protein has significant homologies (56%
      identity and 36% similarity) to the Rad52 protein of Saccharomyces cerevisiae. A
      rad22 disruption strain was constructed which seems to be inviable in a
      homothallic background. Southern blot analyses have shown that the rad22-67
      mutant frequently gives rise to deletions in the mating-type region. These data
      indicate that the Rad22 protein has a function in the repair of DNA double-strand
      breaks.

PMID- 8290357
TI  - Identification of a chicken RAD52 homologue suggests conservation of the RAD52
      recombination pathway throughout the evolution of higher eukaryotes.
AB  - Degenerate oligonucleotides encoding conserved regions of the Rad52 protein of S.
      cerevisiae and its homologue, the Rad22 protein of S. pombe, were used to clone a
      chicken RAD52 counterpart by the polymerase chain reaction. Sequence comparison
      of the chicken and yeast proteins reveals a strongly conserved region between
      positions 40 and 178 of the chicken Rad52 sequence indicating that this part of
      the protein is under strong evolutionary pressure. The first 39 amino acids and
      the 3' end of the chicken Rad52 homologue does not share significant similarity
      with the yeast proteins. High abundance of the mRNA in testis makes it likely
      that the chicken Rad52 protein plays a role in meiotic recombination.

PMID- 8290358
TI  - Preparation of trimers and tetramers of mixed sequence oligodeoxynucleoside
      methylphosphonates and assignment of configurations at the chiral phosphorus.
AB  - Synthesis of stereoregular DNA methylphosphonates has been accomplished for homo
      oligomers, but remains a formidable problem for oligomers of a defined antisense
      target sequence. In this work, four trimer and tetramer deoxynucleoside
      methylphosphonates of mixed sequence (dACA, dCCAA, dAGGG, and dGCAT) were
      prepared by block coupling of diastereomerically pure dimers with either monomers
      or other diastereomerically pure dimers. These oligomers were separated
      chromatographically into individual diastereomers, and the configurations of the
      chiral methylphosphonate linkages were assigned. Three types of methods were used
      to assign configuration of a new methylphosphonate linkage: preparation of the
      same diastereomer through multiple synthetic pathways, base hydrolysis, and acid
      hydrolysis. Hydrolysis of the diastereomerically pure oligomers into component
      dimers and monomers was followed by chromatographic comparison with control
      dimers of known configuration. In all cases studied, oligomers with R
      configurations displayed faster elution from silica gel than did oligomers with
      the respective S configuration. NMR spectra of individual diastereomers of dACA
      were studied, revealing characteristic differences in chemical shifts which may
      prove useful in configurational assignments of longer oligomers. Thus, these data
      provide a methodological basis for synthesis and configurational assignment of
      longer methylphosphonate oligomers to use as antisense probes.

PMID- 8290359
TI  - Cloning and characterisation of the Schizosaccharomyces pombe rad8 gene, a member
      of the SNF2 helicase family.
AB  - The Schizosaccharomyces pombe rad8 mutant is sensitive to both UV and gamma
      irradiation. We have cloned the rad8 gene by complementation of the UV
      sensitivity of a rad8.190 mutant strain. The gene comprises an open reading frame
      of 3.4 kb which does not contain any introns and is capable of encoding a 1133
      amino acid protein of 129 kDa. Deletion of the gene indicates that it is not
      essential for cell viability. Recognisable motifs are present for a nuclear
      localisation signal, a RING finger and helicase domains. The predicted protein is
      a member of the SNF2 subfamily of proteins and shows particular homology to the
      Saccharomyces cerevisiae RAD5 protein. Double mutant analysis demonstrated that
      the rad8 mutant is not epistatic to mutants in the excision repair pathway
      (rad13) or checkpoint pathway (rad9). Analysis of radiation sensitivity though
      the cell cycle indicates that, unlike most other rad mutants, rad8 is most
      sensitive to irradiation during the G1/S period.

PMID- 8290360
TI  - Effects of base substituents on the hydration of B- and Z-DNA: correlations to
      the B- to Z-DNA transition.
AB  - We present a study of how substituent groups of naturally occurring and modified
      nucleotide bases affect the degree of hydration of right-handed B-DNA and left
      handed Z-DNA. A comparison of poly(dG-dC) and poly(dG-dm5C) titrations with the
      lipotropic salts of the Hofmeister series infers that the methyl stabilization of
      cytosines as Z-DNA is primarily a hydrophobic effect. The hydration free energies
      of various alternating pyrimidine-purine sequences in the two DNA conformations
      were calculated as solvent free energies from solvent accessible surfaces. Our
      analysis focused on the N2 amino group of purine bases that sits in the minor
      groove of the double helix. Removing this amino group from guanine to form
      inosine (I) destabilizes Z-DNA, while adding this group to adenines to form 2
      aminoadenine (A') stabilizes Z-DNA. These predictions were tested by comparing
      the salt concentrations required to crystallize hexanucleotide sequences that
      incorporate d(CG), d(CI), d(TA) and d(TA') base pairs as Z-DNA. Combining the
      current results with our previous analysis of major groove substituents, we
      derived a thermodynamic cycle that relates the systematic addition, deletion, or
      substitution of each base substituent to the B- to Z-DNA transition free energy.

PMID- 8290362
TI  - Feature expressions: creating and manipulating sequence datasets.
AB  - Annotation of features, such as introns, exons and protein coding regions in
      GenBank/EMBL/DDBJ entries is now standardized through use of the Features Table
      (FT) language. The essence of the FT language is described by the relation
      'expression-->sequence', meaning that each FT expression evaluates to a sequence.
      For example, the expression M74750:1..50 evaluates to the first 50 bases of the
      sequence with accession number M74750. Because FT is intrinsic to the database
      definition, it can serve as a software- and platform-independent lingua franca
      for sequence manipulation. The XYLEM package makes it possible to create and
      manipulate sequence datasets using FT expressions. FEATURES is a program that
      resolves FT expressions into their corresponding sequences. Annotated features
      can be retrieved either by feature key or by expression. Even unannotated
      portions of a sequence can be retrieved by user-generated FT expressions.
      Applications of the FT language include retrieval of subsequences from large
      sequence entries, generation of chromosome models or artificial DNA constructs,
      and representation of restriction maps or mutants.

PMID- 8290361
TI  - Predicted common structural features of DNA-binding domains from Ets, Myb and HMG
      transcription factors.
AB  - The Ets family of transcription factors shares a 85 amino acid domain, named the
      ETS domain, which appears responsible for their DNA binding activity. This domain
      did not show any clear similarity with already known DNA binding motifs.
      Hydrophobic Cluster Analysis (HCA), a sensitive method able to detect protein
      structural relationships even at low sequence identity, was chosen in order to
      compare the ETS domain with other conventional DNA binding motifs. HCA analysis
      combined with known three-dimensional NMR data, suggests that the ETS domain may
      be structurally related to the Myb DNA binding domain and possibly to the HMG
      one. Indeed, the ETS domain is likely to contain two helix-loop-helix motifs.

PMID- 8290363
TI  - Scanning force microscopy of circular and linear plasmid DNA spread on mica with
      a quaternary ammonium salt.
AB  - Scanning force microscopy (SFM) offers the potential for subnanometer resolution
      in the investigation of nucleic acids, proteins, and their complexes. SFM is not
      bound by the requirement of classical transmission electron microscopy (TEM) for
      contrast enhancement through shadow casting or negative staining. A primary
      challenge, however, has been the reproducible fixation of samples on an
      atomically flat surface such as mica. We have developed a method for the routine
      imaging by SFM of supercoiled, relaxed, and linearized plasmid DNA, immobilized
      on freshly cleaved mica through the spreading action of
      benzyldimethylalkylammonium chloride (BAC) at micromolar concentrations. A
      reproducibly high yield of well-spread, dispersed molecules is obtained and
      background contamination is minimal. The contour lengths of the relaxed and
      linearized molecules imaged in air agree well with the helical rise (3.4 A/bp) of
      B-DNA in solution. We have also introduced the use of quantitative image analysis
      of SFM images to determine apparent molecular width and height over the entire
      molecular path.

PMID- 8290364
TI  - The MHC class II E beta promoter: a complex arrangement of positive and negative
      elements determines B cell and interferon-gamma (IFN-gamma) regulated expression.
AB  - The 5' proximal region of the E beta gene was studied with respect to B lymphoid
      expression and responsiveness to cytokines, revealing a complex array of general
      and cell type specific cis-elements and factors. Full lymphoid activity and
      response to interferon-gamma (IFN-gamma) is generated by the concerted action of
      the MHC boxes (H, X and Y) and additional elements. Combinatorial interactions
      between elements and their cognate factors are indicated by several lines of
      evidence. Thus, mutations within the X box in the promoter context are strongly
      deleterious to both B lymphoid activity and IFN-gamma regulation. However, the X
      box alone has minimal lymphoid activity upon heterologous promoters. Data from
      deletion, insertion and site directed mutagenesis demonstrate that sequences
      extending approximately 35 bp 5' of the X box (designated as Cytokine Response
      Sequence--CRS) have a dual role: they are required for cytokine-regulated
      expression as well as serving as an enhancer element for cell-specific
      constitutive expression. A region that carries X and CRS permits both lymphoid
      activity and IFN-gamma response. In contrast, sequences that include X and the
      downstream Y box are constitutively active in all cell types tested. Combination
      of the sequences both upstream and downstream of the X box results in a tissue
      specific and cytokine-regulated enhancer of full strength. In vivo competition
      studies show that titratable trans-acting factors, shared by Class I and Class II
      promoters, mediate the CRS-dependent IFN-gamma response. We report here the
      identification of novel nuclear complexes that bind to the CRS and recognize
      sites which correlate with its negative or positive elements. One of these
      complexes is present in B lymphoid cells only. Three other CRS complexes that are
      upregulated by either IFN-alpha and IFN-gamma are competed by a non-Class II, IFN
      alpha stimulated response element (ISRE), providing evidence for the functional
      interconnection of these cytokines.

PMID- 8290365
TI  - The relationship between mutation rates for the (C-G)-->(T-A) transition and
      features of T-G mispair structures in different neighbor environments, determined
      by free energy molecular mechanics.
AB  - The results of this theoretical study combining sequence analysis and
      minimization with integral equation liquid structural methods indicate that the
      local sequence context of a T-G wobble mismatch influences the local conformation
      of the helix, and that conformational alterations are correlated with mutational
      activity. Studies on the mismatch in four different 5' and 3' neighbor contexts
      indicate that the nature of the 5' base to the thymine of the mispair is probably
      the single most critical factor in determining the structural features that
      facilitate or discourage mutations. When cytosine is the 5' neighbor, the helix
      adopts a mostly BII conformation, whereas a 5' guanine preserves the canonical
      BI. Structures that vary little from the BI structure on the incorporation of the
      mismatch have sequences that correspond to lower rates of transition, whereas
      those with mostly BII conformations, have sequences with high mutation rates.
      Subtle variations in stacking patterns around the mismatch precipitate a
      structural Domino-effect, with a variety of changes in conformation. The helix
      opens at the mismatch with increased roll angle and propeller twist, causing the
      thymine to migrate into the major groove and the guanine into the minor groove,
      exposing the heteroatomic groups to the solvent in the major and minor grooves,
      respectively, and allowing for some unusual hydrogen bonds. These alterations
      show a tentative correlation with mutation rates, implying that stacking and
      structure around the mismatch are important features in the discrimination by
      proofreading activities of canonical W-C and wobble mismatch base pairs during
      replication-repair. Variations in the C1'-C1' distances, high propeller twists,
      changes in the electrostatic complementarity leading to unusual hydrogen bonding
      patterns probably all correlate with detectability.

PMID- 8290366
TI  - Universal immuno-PCR for ultra-sensitive target protein detection.

PMID- 8290367
TI  - A simple method to renature DNA-binding proteins separated by SDS-polyacrylamide
      gel electrophoresis.

PMID- 8290368
TI  - Separation of up to 1000 bases on a modified A.L.F. DNA sequencer.

PMID- 8290369
TI  - Reduced occurrence of chimeric YACs in recombination-deficient hosts.

PMID- 8290370
TI  - Determination of plasmid copy number in yeast transformants by means of agarose
      plugs.

PMID- 8290371
TI  - Cloning and characterization of the C.elegans histidyl-tRNA synthetase gene.

PMID- 8290372
TI  - Infant mortality revisited.

PMID- 8290373
TI  - Fumes from the spleen.

PMID- 8290374
TI  - So what?

PMID- 8290375
TI  - The Dutch famine birth cohort study: design, validation of exposure, and selected
      characteristics of subjects after 43 years follow-up.
AB  - A historical birth cohort study of 1116 women born between August 1 1944 and
      April 15 1946 in the Wilhelmina Gasthuis hospital in Amsterdam, the Netherlands,
      was set up to study the short- and long-term effects of a limited period of
      extreme nutritional deprivation in the winter of 1944-1945 in the Western
      Netherlands. The degree of food deprivation is evidenced by a dramatic decline in
      third trimester pregnancy weight gain and infant birthweight. All women were
      traced and 84% (683/813) of survivors presently resident in the Netherlands
      agreed to be interviewed in their homes. There were no differences in
      characteristics at birth between interviewed and uninterviewed survivors. The
      women who were interviewed had 1299 offspring and were able to recall birthweight
      of all of them. Additional birthweight information from hospital and well-baby
      clinic (WBC) records is available for about half of the offspring. Since the
      famine was imposed on the entire population of a well-defined area, whose
      opportunities to obtain food elsewhere were severely restricted, and the women
      from this hospital cohort were predominantly lower middle class, the relationship
      between fetal nutrition and subsequent health outcomes in this cohort is not
      likely to be confounded by unmeasured attributes related to social class. In
      addition, selective losses to follow-up could be excluded, which makes the Dutch
      famine birth cohort a valuable resource for future studies in perinatal
      epidemiology.

PMID- 8290376
TI  - Antenatal cystic fibrosis carrier screening--whether, when and how?
AB  - Population screening for carriers of cystic fibrosis (CF) is now possible. Such
      screening may have both advantages and disadvantages and hence must be evaluated
      before it becomes routine practice. As the potential benefits of screening are
      wide and the drawbacks may include psychological effects, a combination of
      approaches is needed to assess screening thoroughly instead of only counting
      numbers of terminations or carrier tests. We describe the issues concerned and
      our methodology for a rigorous evaluation of population antenatal carrier
      screening for cystic fibrosis.

PMID- 8290377
TI  - Different effects of maternal and paternal education on early mortality in
      Norway.
AB  - In order to separate the effects of maternal and paternal education on pregnancy
      outcome, a total population of 97,526 single, firstborn infants and their parents
      was studied. Census information from 1980 was linked to the Medical Birth
      Registry for 1978-82. Children of parents with high education (> 12 years) were
      the most likely to survive the first year of life. There was a linear association
      between parental education and infant mortality. Examining parental education
      jointly, it was found that the father's educational level had the greatest impact
      on stillbirth. Mother's educational level seemed to be more closely associated
      with postneonatal mortality. Possible mechanism to explain the association
      between educational level and infant mortality are discussed.

PMID- 8290378
TI  - Confounding or intermediate effect? An appraisal of iatrogenic bias in perinatal
      AIDS research.
AB  - Many epidemiological reports present estimates of exposure effect adjusted for a
      host of variables thought to be risk factors for the disease. The term iatrogenic
      bias is proposed to denote bias introduced by the analyst when inappropriately
      controlling for variables as though they were confounders. The focus of this
      commentary is iatrogenic bias resulting from the control of variables
      intermediate in the causal pathway between exposure and disease. Perinatal
      epidemiological studies are particularly vulnerable, and iatrogenic bias will
      typically mask or diminish the true effect of the exposure. The problem is
      illustrated with three examples from the field of perinatal AIDS epidemiology. It
      is recommended that researchers carefully scrutinize each variable considered for
      adjustment and use path diagrams to sort out causal pathways. In some instances,
      it may be most appropriate to present both adjusted and unadjusted estimates of
      effect.

PMID- 8290379
TI  - Amniotic band syndrome: a population-based study in two Australian states.
AB  - A search for cases of amniotic band syndrome was made in two population-based
      Australian birth defects registries, using defined selection criteria. Over a
      period of 4 years in Western Australia and 5 years in South Australia, 25 cases
      of amniotic band syndrome had been identified as such by the two registries, and
      an additional 15 new cases were identified by the study selection process, giving
      an annual prevalence of amniotic band syndrome over the study period of 2.03 per
      10,000 births. Similar proportions of male and female infants were affected,
      although the syndrome was more common in mothers younger than 25 years of age,
      and in first births. Limb defects only (upper and/or lower) were found in 24
      cases, limb-body-wall defects in four cases, and complex craniofacial and other
      malformations in 12 cases. A heightened awareness of the syndrome should enhance
      the identification of amniotic band syndrome, which has implications for genetic
      counselling, and our understanding of the aetiology and pathogenesis of this
      condition.

PMID- 8290380
TI  - Recurrent pregnancy loss as an indicator for increased risk of birth defects: a
      population-based case-control study.
AB  - Stillbirths and spontaneous abortuses have higher rates of birth defects than
      liveborn infants. The relationship between a woman's previous pregnancy loss and
      the risk of birth defects in the offspring has not been adequately examined,
      however. Using data from a population-based case-control study, we assessed
      whether one or more previous pregnancy loss was associated with increased birth
      defect risks. Case subjects were 4918 infants with serious births defects
      diagnosed in the first year of life and ascertained by the Metropolitan Atlanta
      Congenital Defects Program from 1968 to 1980. Control subjects were 3028 normal
      liveborn infants frequency-matched to case infants by race, hospital and period
      of birth. Among case and control infants whose mothers had already had at least
      one previous pregnancy, reported pregnancy losses (stillbirths and miscarriages)
      were associated with elevated risks of birth defects (odds ratios for one
      pregnancy loss of 1.24, two pregnancy losses of 1.49, and three or more pregnancy
      losses of 1.62, P < 0.0001 for trend). This association held after considering
      several potential confounders using logistic regression analysis. When specific
      defects were examined, many exhibited this association, notably hydrocephalus,
      and some cardiovascular, genital and limb defects. We estimate that the risk of
      serious birth defects increases from 2.5% for infants of women with no prior
      pregnancy loss to 4.2% for infants of women with three or more pregnancy losses.
      This finding has both clinical implications for pregnancy counselling and
      pathogenetic implications related to birth defect aetiology.

PMID- 8290381
TI  - Perinatal predictors of ocular morbidity in school children who were very low
      birthweight.
AB  - Two hundred children from one neonatal intensive care unit (NICU), who were very
      low birthweight (VLBW), were examined at approximately 9 years of age and
      compared with a control group of normal birthweight children. Visual morbidity
      was significantly higher among children who were very low birthweight. Binocular
      visual acuity of 6/9 or worse was noted in 21 (10.5%), strabismus in 38 (19%) and
      regressed retinopathy of prematurity (ROP) in 13 (6.7%) of these children. A
      history of seizures in the perinatal period was highly correlated with poor
      visual acuity. Independently significant factors associated with strabismus
      included clinically diagnosed intraventricular haemorrhage, a maternal history of
      neonatal death, transfer from another hospital, bronchopulmonary dysplasia and
      necrotising enterocolitis. Perinatal variables that correlated with regressed ROP
      included birthweight, time from birth to admission to the NICU, necrotising
      enterocolitis and a history of maternal smoking during the pregnancy. When
      screening for ocular abnormalities among children who were born preterm,
      particular attention should be given to children with these risk factors.

PMID- 8290382
TI  - Age at neonatal death in Ontario, 1979-1987: implications for the interpretation
      of mortality markers.
AB  - Recent evidence concerning time trends in infant mortality rates suggests faster
      falls in early compared with late deaths. This may be due to rapid advances in
      neonatal care. This study was undertaken to examine the timing of neonatal death
      in Ontario between 1979 and 1987. Trends with time, gestational age and type of
      birth hospital were examined. Evidence suggests that, controlling for level of
      birth hospital and gestational age, there was a time trend of an increasing
      proportion of late neonatal deaths. This suggests that early neonatal mortality
      was decreasing more rapidly than late neonatal mortality. Controlling for year of
      birth and gestational age, it was observed that the proportion of late neonatal
      deaths was higher for those born in a tertiary rather than community hospital. In
      combination, these findings suggest that, due to advances in neonatal care, a
      disproportionately high number of early neonatal deaths are increasingly being
      prevented. The findings have implications for the interpretation of routinely
      available mortality markers. The authors conclude that early neonatal death rate
      may be becoming a less useful marker and that a measure of perinatal mortality
      which includes late neonatal deaths would be a useful addition to the currently
      collected mortality markers.

PMID- 8290383
TI  - Examining potential demographic risk factors for congenital cardiovascular
      malformations on a time-developmental model.
AB  - A descriptive epidemiological study of congenital cardiovascular malformations
      (CCM) was performed to evaluate the use of a model which groups selected cardiac
      lesions according to time of embryonic origin. Infants born from 1983-1986 to
      residents of New York State excluding New York City and reported to the
      Congenital Malformation Registry (CMR) were first grouped into those with (n =
      299) and without (n = 4424) chromosomes anomalies. Infants were then categorised
      according to the time of gestation of their earliest occurring CCM into one of
      the seven cardiac groups of the model. The categories were analysed by infant
      race, gender, birthweight, gestation, maternal age and education, and the
      presence of additional malformations. The group without chromosomal anomalies
      showed an increasing proportion of non-whites, females, and preterm births and a
      decreasing proportion of infants with other malformations in the embryonically
      later categories. The group with chromosomal anomalies was too small to exhibit
      any significant demographic patterns. The findings suggest associations between
      characteristics of the infant and the embryonic period in which the CCM occurred,
      thus demonstrating the usefulness of a time-based model. Further research should
      concentrate on confirming these associations with more complete data and on
      investigating their biological bases.

PMID- 8290384
TI  - Trends in Down's syndrome prevalence in California, 1983-1988.
AB  - Trends in the prevalence of Down's syndrome in livebirths were examined in
      California from 1983 to 1988, a time period when prenatal screening and
      subsequent termination of Down's syndrome pregnancies among women under 35 years
      of age was increasing. In the population-based ascertainment areas of the
      California Birth Defects Monitoring Program (CBDMP), 1058 infants with Down's
      syndrome were identified, giving a crude prevalence of 1.03 (95% confidence
      interval [CI]: 0.97, 1.09). The risk ratio for 1988 compared with 1983, after
      adjusting for maternal age and other confounders, was 0.98 (95% CI: 0.78, 1.23),
      showing that there was no change in livebirth prevalence over this period. The
      data were also examined for mothers under 35 years of age to determine whether
      increasing use of prenatal screening leading to termination masked an increase in
      prevalence. A modest increase was seen.

PMID- 8290385
TI  - Factors limiting the effectiveness of prenatal screening for anencephaly and
      spina bifida in a high-risk area.
AB  - The effectiveness of a prenatal screening programme in reducing the birth
      prevalence of anencephaly and spina bifida (ASB) is influenced by three principal
      factors: the proportion of affected pregnancies screened (uptake), the proportion
      of affected pregnancies detected on screening (sensitivity) and the proportion of
      affected pregnancies terminated when detected (compliance). The purpose of the
      study was two-fold: to develop an epidemiologically-based method for the
      retrospective monitoring of these three factors and to attempt to quantify their
      relative importance in relation to the outcome of screening. Data on births and
      terminations associated with ASB for the period 1976-1986 were obtained from the
      Glasgow Register of Congenital Anomalies and from the Department of Medical
      Genetics, Yorkhill Hospitals. Increasing proportions of affected pregnancies
      screened, detected and terminated were observed, to a greater degree for
      anencephaly than for spina bifida. The relationships between uptake, sensitivity,
      compliance and terminations are described in the form of a simple arithmetic
      expression. In policy terms, further efforts are required to increase all three
      in order to improve the effectiveness of screening for spina bifida.

PMID- 8290386
TI  - Effect of the nonsteroidal antiandrogen nilutamide on adrenal androgen secretion.
AB  - The nonsteroidal androgen-receptor antagonist nilutamide has previously been
      shown to inhibit adrenal androgen steroidogenesis in patients with prostatic
      carcinoma treated in combination with an LHRH agonist. In order to understand
      better the mechanisms subserving this observation, we have studied the effects of
      nilutamide alone on the serum concentrations of androstenedione (A),
      dehydroepiandrosterone (DHEA), and DHEA-sulphate (DHEA-S) in 12 patients with
      prostatic cancer and compared them with those achieved in 21 patients treated
      with the agonist D-Trp-6-LHRH. In addition, the adrenocorticotropic hormone
      (ACTH)-stimulated adrenal response and the thyrotropin releasing hormone (TRH)
      stimulated prolactin (PRL) response observed in the patients treated with
      nilutamide were compared with a control group of healthy age-matched controls. No
      significant variation in the basal concentrations of adrenal androgens occurred
      either within or between both treatment groups. In response to ACTH, a decreased
      17-alpha hydroxyprogesterone (17-OHP) accumulation and an augmented A/17-OHP
      ratio were observed in the antiandrogen group (P < 0.05 for both), suggesting the
      partial removal of the 17,20 lyase block which was distinctive of the untreated
      controls, while no significant difference was found for other steroids. Basal PRL
      levels were not affected by the antiandrogen, but the response to TRH was
      increased. We conclude that no significant inhibition of adrenal androgen
      secretion occurs after nilutamide or LHRH agonist treatment. Rather,
      administration of the antiandrogen alone may partially remove the physiological
      decrease in adrenal androgen secretion observed in the elderly.

PMID- 8290387
TI  - Mortality trend from prostate cancer in The Netherlands (1950-1989).
AB  - The trend in prostate cancer mortality in The Netherlands was studied, using data
      from the National Causes of Death Registry of the Central Bureau of Statistics.
      During the period 1950-1989, the age-adjusted mortality rate showed a steady rise
      from 20.5 to 30.6 per 100,000 man-years. A multiplicative model was used to
      examine possible period effects and birth-cohort effects separately. This
      analysis demonstrated that the increase in prostate cancer mortality is largely
      due to a birth-cohort effect, though calendar time of death may have had a slight
      effect as well. Among Dutch men, a continuous increase of mortality from prostate
      cancer was found in consecutive birth cohorts. This finding is in contrast with
      that of comparable studies in other Western countries, in which a peak mortality
      rate was found for the cohort born at the end of the 19th century with
      stabilizing or declining rates for later birth cohorts.

PMID- 8290388
TI  - Estramustine potentiates the radiation effect in human prostate tumor transplant
      in nude mice.
AB  - In this study, we have investigated the combined effect of estramustine treatment
      and external beam radiation on human prostatic cancer tumor cells (DU 145)
      transplanted in nude mice. The treatment was given according to two different
      schedules. In the first treatment regimen, estramustine was administered
      intraperitoneally (i.p.) intermittently for 20 days. The radiation therapy, which
      was started on day 9, was given with 6 Gy fractions during an 11-day-long period
      to a total dose of 36 Gy. The combination treatment (estramustine + radiation)
      resulted in a significant tumor growth retardation as compared to the control
      group. This pronounced effect was seen neither with radiation alone nor with
      estramustine alone. In order to further extend the radiation treatment time, a
      second therapy regimen was employed. In this part of the study, estramustine was
      administered i.p. intermittently for 26 days. The radiation therapy, which was
      started on day 6, was given with 4 Gy fractions during a 21-day-long period to a
      total dose of 40 Gy. Under these conditions, a significant tumor growth
      retardation was disclosed, when comparing the combination treatment (estramustine
      + radiation) with radiation alone. The tumors were analyzed for content of
      necrosis and proliferative activity. The largest proportion of necrosis was seen
      in the combination (estramustine + radiation) treatment group. Also, the tumors
      from this group expressed a decreased proliferative activity. The data indicate
      that estramustine acts as a radiosensitizing agent in human prostatic cancer
      cells in vivo. The radiosensitizing properties of the drug encourage further
      studies with respect to clinical application.

PMID- 8290389
TI  - Effect of epidermal growth factor on prostate cancer cell line PC3 growth and
      invasion.
AB  - Elevated levels of epidermal growth factor (EGF) and epidermal growth factor
      receptor (EGF-R) have been demonstrated in prostate cancer cell lines and
      clinical specimens suggesting a role for polypeptide growth factors in prostate
      tumor cell growth and invasion. To more clearly define the role of EGF in
      prostate cancer invasion, we undertook a series of studies utilizing the PC3
      prostate cancer cell line, an aggressive, hormone-independent cell line derived
      from a metastatic lesion. No statistical differences were noted in the growth of
      PC3 cells under serum-free conditions when EGF (10(-10) M-10(-8) M) or monoclonal
      anti-EGF-R antibody (10(-11) M-10(-8) M) were added. Utilizing the Boyden chamber
      microinvasion assay, EGF supplemented cells demonstrated a statistically
      significant augmentation in invasion (P < 0.05) when compared to control cells at
      each time point in the study. With increasing length of exposure to EGF, the
      number of concentrations that produced significant invasion increased: day 1 (10(
      8) M), day 3 (10(-8), 10(-9) M), and day 5 (10(-7), 10(-8), 10(-10) M). Northern
      blot analysis of EGF supplemented cells revealed an increase in expression of
      urokinase plasminogen activator (uPA) RNA, a serine protease involved in the
      regulation of pericellular proteolysis and membrane degradation. Protein analysis
      confirmed these findings. Statistically significant inhibition of invasion by
      anti-uPA antibodies was demonstrated for EGF-stimulated and PC3 control cells.
      Our results demonstrate that certain concentrations of EGF augment invasion in
      the PC3 cell line. This enhancement of invasion occurs in part by an
      overproduction of uPA, an extracellular protease. These findings suggest that the
      autocrine production of EGF may potentiate tumor cell invasion.

PMID- 8290390
TI  - Phantom pain.

PMID- 8290391
TI  - Rupture of brachial artery.

PMID- 8290392
TI  - Status of baclofen pump.

PMID- 8290393
TI  - Patellar dislocation.

PMID- 8290394
TI  - AAOS initiatives address health system reform.

PMID- 8290395
TI  - The anterior acromial approach for antegrade intramedullary nailing of the
      humeral diaphysis.
AB  - At three institutions, 71 humeral intramedullary nails were inserted into the
      shoulder; 67 were reviewed at 6 months and at completion of treatment. Fifty-one
      utilized the anterior acromial approach and 16 were inserted lateral to the
      acromion. Shoulder motion was rated as: excellent (asymptomatic and within 15
      degrees of normal); good (normal daily function within normal motion); and poor.
      Nails were also inserted into the humeral diaphysis of eight cadaver shoulders.
      Fifty-one nails were inserted via the anterior acromial incision; 48 were graded
      as excellent, one as good, and two with traumatic axillary neuropathy and reflex
      sympathetic dystrophy as poor: Sixteen nails were inserted lateral to the
      acromion; 8 were rated, 7 good, and 1 poor. Motion returned in an average of 17
      weeks (range:0-29). The greatest clinical concern is not ultimate shoulder
      function, but the rate of return. The authors conclude that either the anterior
      acromial approach or an extraarticular entry portal must be utilized for
      antegrade humeral diaphyseal nailing.

PMID- 8290396
TI  - Fibular nonunion in combination with fractures of the tibia.
AB  - Seventeen cases of fibular nonunion or delayed union were seen in our institution
      from 1985 to 1990. All but one of these cases were associated with nonunion of
      the tibia which was diagnosed radiologically and/or surgically. The fibula
      characteristically heals before the tibia; therefore, if the fibula is slow in
      healing or showing nonunion, more intensive investigation of the tibia for occult
      nonunion, or delayed union, should be done to determine whether early surgical
      intervention would be necessary to avoid prolonging the course of treatment.
      Nonunion of the fibula may indicate instability of the fractured tibia. The
      authors have examined the relationship of this mutual nonunion and recommend
      careful observation of the fibular healing in associated fractures of the tibia
      and fibula.

PMID- 8290397
TI  - Postoperative results of rheumatoid arthritis patients on methotrexate at the
      time of reconstructive surgery of the hand.
AB  - We conducted a retrospective chart review examining the frequency of local
      postoperative infection and poor wound healing of 15 methotrexate-treated
      rheumatoid arthritis patients undergoing 155 procedures during 39 surgeries. The
      patients were compared to a group of rheumatoid patients not on methotrexate who
      underwent similar reconstructive surgery of the hand. The patients taking
      methotrexate were followed postoperatively for a minimum of 10 weeks, with a mean
      follow-up time of 1 year, 42 weeks. There were no postoperative complications
      that would lead to the belief that the administration of methotrexate results in
      poor wound healing or leaves the patient more susceptible to postoperative
      infection. Our findings and a review of the literature support a continuation of
      methotrexate therapy in rheumatoid arthritis patients scheduled for
      reconstructive surgery of the hand and wrist.

PMID- 8290398
TI  - The thoracic outlet syndrome.
AB  - The thoracic outlet syndrome is a compressive neurovascular condition of the
      upper extremity. The neurologic, arterial, and venous structures may be affected
      individually or in combination in any given patient. Multiple surgical and
      medical subspecialists may be involved in the care of these patients, including
      orthopedic, vascular, and thoracic surgeons, neurosurgeons, and neurologists. The
      topic is extremely controversial; some authors believe that this is a very common
      condition, while others question the existence of the syndrome. There is
      disagreement concerning the diagnosis, workup, and proper therapeutic management.
      The purpose of this article is to critically review and analyze the literature on
      this subject.

PMID- 8290399
TI  - A special high tibial osteotomy technique for treatment of unicompartmental
      osteoarthritis of the knee.
AB  - Tibial osteotomy is a well-established procedure for treatment of the varus
      osteoarthritic knee. A special new technique of oblique tibial osteotomy at the
      level of the tibial tubercle, preserving the medical cortex and iliotibial band,
      is presented which allows partial weight bearing the first postoperative day.
      Postoperatively the femorotibial alignment should be 5 degrees to 7 degrees of
      valgus in elderly patients. Because in younger individuals the intact iliotibial
      band is a strong restraint against varus deformity, we seek to correct to 3
      degrees to 5 degrees of valgus in these patients. Of 172 cases treated with this
      technique between 1982 and 1986, 50 patients were retrospectively reviewed. After
      a follow-up period of 6 months to 3 years, pain was relieved in 46 patients.
      Complications consisted of 5 secondary wound healings, including 2 superficial
      infections, 1 tibial plateau fracture, and 3 varus recurrences.

PMID- 8290400
TI  - Three central acetabular fracture-dislocations secondary to metabolically induced
      seizures in ESRD patients.

PMID- 8290401
TI  - Psoriatic arthritis of the knee treated with synovectomy.

PMID- 8290402
TI  - Association of metatarsus adductovarus (skew foot) with Angelman's (Happy Puppet)
      syndrome.

PMID- 8290403
TI  - Recurrent cervical subluxations in a patient with gout and endstage renal
      disease.

PMID- 8290404
TI  - Metallic wear debris in acetabular osteolysis in a mechanically stable cementless
      total hip replacement: report of a case.
AB  - Wear debris has evolved as the primary etiology of mechanical loosening of
      cemented as well as uncemented total hip arthroplasty. Osteolysis results from
      particle formation, and this has been most commonly reported to be secondary to
      polyethylene wear debris. This article demonstrates that metallic particle debris
      will also result in significant osteolysis. The two sources in this case are
      cobalt-chromium (Co-Cr) particles from the acetabular component and titanium
      alloy (Ti) particles from the Morse taper junction and the Ti-alloy femoral head.
      However, it is likely that polyethylene debris also contributed to the
      osteolysis, because a titanium head was used and we know this results in
      increased poly wear.

PMID- 8290405
TI  - Answer please. Osteofibrous dysplasia.

PMID- 8290406
TI  - A risk-benefit analysis for the treatment of hypertension.

PMID- 8290408
TI  - Homozygous variegate porphyria: an evolving clinical syndrome.
AB  - Variegate porphyria is one of the most frequently encountered genetic conditions
      in South Africa. It is inherited as an autosomal dominant disease and in excess
      of 300 heterozygous cases have been studied by the Cape Town unit. Despite this,
      the homozygous condition has not previously been encountered in South Africa. We
      report two cases of homozygous variegate porphyria, one of whom represents the
      first South African case. We delineate a syndrome principally characterized by
      growth retardation, developmental delay, epileptic seizures, photosensitivity and
      an abnormal porphyrin excretion pattern. In addition we describe, in one case,
      two features not previously reported: skin disease in areas unexposed to light
      and a severe sensory neuropathy which may account at least in part for the hand
      deformities of this disorder.

PMID- 8290409
TI  - Open access endoscopy: is the lost outpatient clinic of value?
AB  - To test the value of an outpatient visit in patients with dyspepsia, 79 patients
      considered suitable for open access endoscopy by their general practitioners were
      instead seen in the medical outpatient clinic first. In 35 patients immediate
      endoscopy was seen as an inappropriate investigation and 23 of these were spared
      endoscopy. In 11 patients important extra diagnoses were made in the clinic which
      would have been delayed or missed had the patients been sent straight for open
      access endoscopy. Sixty-eight per cent of patients, when asked by questionnaire,
      said they preferred to be seen in the clinic first rather than come for open
      access endoscopy. These results lend support to the traditional medical clinic
      appointment followed by endoscopy if and when appropriate rather than the open
      access endoscopy system.

PMID- 8290407
TI  - Methotrexate in rheumatoid arthritis: can current knowledge and experience
      justify its use as a first-line disease-modifying agent?

PMID- 8290410
TI  - Bartter's syndrome in two generations of an Irish family.
AB  - We report four cases of Bartter's syndrome in two consecutive generations of an
      Irish family. Diagnoses were made on the basis of characteristic clinical
      features, blood and urine biochemistry with additional evidence from renal biopsy
      in one case. The aetiology, treatment and inheritance of the syndrome are
      discussed.

PMID- 8290412
TI  - Giant hydronephrosis masquerading as massive ascites.
AB  - A case of unilateral giant hydronephrosis containing about 20 litres of old
      haemorrhagic fluid, clinically simulating massive ascites, is reported. The role
      of preceding abdominal trauma in the pathogenesis and the rapidity of the disease
      process is discussed.

PMID- 8290411
TI  - A study of plasma sodium levels in elderly people taking amiloride or triamterene
      in combination with hydrochlorothiazide.
AB  - This study was performed to compare the effect of one month's treatment with
      hydrochlorothiazide (25 mg) in combination with either amiloride (2.5 mg) or
      triamterene (50 mg) on plasma sodium levels in elderly people in institutional
      care. Fifty residents of NHS nursing or social service residential care
      established on diuretics for congestive cardiac failure and aged 64 years or over
      were recruited. Forty-one patients were included in the final data analysis.
      Patients on hydrochlorothiazide/amiloride had a significantly lower plasma sodium
      (137 vs 139 mmol/l, 95% confidence interval for difference between medians 0-2
      mmol/l) than those on hydrochlorthiazide/triamterene (P = 0.01). In equivalent
      potassium-retaining doses, amiloride is associated with significantly lower
      plasma sodium levels than triamterene, when given in combination with
      hydrochlorothiazide in elderly patients with congestive cardiac failure. This
      finding adds weight to uncontrolled observations implicating thiazide/amiloride
      diuretic combinations in causing serious hyponatraemia. This danger, although
      uncommon, should perhaps influence prescribing habits in an at-risk population.

PMID- 8290413
TI  - Sexual abuse of the elderly mentally ill.
AB  - Sexual abuse of the elderly may occur more commonly than is recognized. Reasons
      for the neglect of this area and possible risk factors are discussed. A
      definition of elder sexual abuse is proposed, and four case histories, each of
      which raises various issues about the nature, detection and management of sexual
      abuse, are described. In the absence of procedures for dealing with elder sexual
      abuse, professional staff need to be open to its occurrence and to be prepared to
      carry out thorough, sympathetic, collaborative assessments of both parties
      involved where it is suspected.

PMID- 8290414
TI  - Clinical tutor--mark II?

PMID- 8290415
TI  - Learning medical ethics with our new neighbours.

PMID- 8290416
TI  - Thyroid storm in a young woman resulting in bilateral basal ganglia infarction.
AB  - We describe a 30 year old woman who presented with thyroid storm. She had non
      specific symptoms and few clinical signs of hyperthyroidism despite markedly
      raised thyroid hormone concentrations. Soon after admission her behaviour became
      abnormal and her level of consciousness deteriorated. Despite the rapid
      restoration of thyroid hormone concentrations to normal using conventional
      therapies, and correction of hypoxia resulting from acute pulmonary oedema, her
      level of consciousness did not improve. Cranial CT scanning revealed extensive
      bilateral basal ganglia infarction, a previously unreported complication of
      thyroid storm. This observation suggests that thyroid storm may predispose to
      hypoxic neurological damage.

PMID- 8290417
TI  - Recurrent infective endocarditis.
AB  - Infective endocarditis is a serious disease associated with high mortality.
      Patients surviving recurrent bouts of infective endocarditis are reported
      infrequently. We report on a non-drug abuser patient who experienced seven
      episodes of infective endocarditis--the largest number reported to our knowledge
      in a single non-drug abuser patient.

PMID- 8290418
TI  - Intestinal prolapse through the vagina.
AB  - We describe the case of a 68-year-old woman who presented with an acute onset
      spontaneous vaginal vault rupture and intestinal prolapse through the vagina.
      Results of a literature survey are presented and the causes of vaginal vault
      rupture are discussed.

PMID- 8290419
TI  - Postpartum pain due to thrombosed varicose veins of the round ligament of the
      uterus.
AB  - Postpartum thrombosis of varicose veins of the round ligament may present in a
      clinical picture similar to an irreducible inguinal hernia. Two such unusual
      cases are reported. One patient underwent surgery while the other, with a
      presumptive diagnosis of the same condition, was observed, with no complications
      occurring in both patients. This condition has not to my knowledge been
      previously reported. The increased incidence of both varicose veins and
      thrombosis in the postpartum period should alert the physician to the diagnosis
      of such conditions.

PMID- 8290420
TI  - Uterocutaneous fistula.
AB  - Fistulous communications of the uterus are relatively unknown. We report in this
      paper the first case to our knowledge of uterocutaneous fistula which developed
      following a septic abortion induced by introduction of Laminaria tent into the
      uterus.

PMID- 8290421
TI  - Type IV renal tubular acidosis associated with Alport's syndrome.
AB  - A case of hereditary nephritis with mild reduction of renal function associated
      with renal tubular acidosis type IV is described. The patient was admitted with
      life-threatening hyperkalaemia. To our knowledge, type IV renal tubular acidosis
      has not been reported previously in association with Alport's syndrome in an
      adult patient.

PMID- 8290422
TI  - Abdominal wall abscess--an unusual primary presentation of a transverse colonic
      carcinoma.
AB  - Carcinoma of the transverse colon presenting as an abscess of the anterior
      abdominal wall is a rare occurrence. Such a case is presented, where all
      investigations failed to show the nature of the lesion. The literature has been
      reviewed and the pathology that characterizes such lesions, and their management
      in the light of their favourable prognosis, is discussed. Occult colonic
      carcinoma should be considered in the differential diagnosis of such abscesses.

PMID- 8290424
TI  - Recovery of adrenocortical function following treatment of tuberculous Addison's
      disease.

PMID- 8290423
TI  - A case of Churg-Strauss vasculitis complicated by small bowel necrosis.
AB  - A case of Churg-Strauss syndrome causing mesenteric intestinal ischaemia and
      small bowel necrosis is described in a 29-year-old man. Despite conservative
      management, the patient's condition deteriorated and he underwent five
      laparotomies. Small and medium-sized arteries within the mesentery and lymph
      nodes showed necrotizing vasculitis. Currently he is doing well on oral nutrition
      and medical management.

PMID- 8290425
TI  - Guillain-Barre syndrome in a patient with chronic lymphocytic leukaemia.

PMID- 8290426
TI  - Anti-epileptic therapy and fatal chickenpox.

PMID- 8290427
TI  - Parenteral nutrition in adult intensive care.

PMID- 8290428
TI  - New markers of bone and collagen turnover in children and adults with growth
      hormone deficiency.
AB  - Serum bone Gla protein (BGP), a marker of osteoblastic function, serum
      carboxyterminal cross-linked telopeptide of type I collagen (ICTP), a marker of
      bone resorption, and serum aminoterminal propeptide of type III procollagen
      (PIIINP) levels, an index of collagen synthesis, were determined in seven
      children and eight adults with congenital growth hormone deficiency (GHD). In
      children with GHD, serum BGP (mean +/- s.e.: 12.9 +/- 0.7 ng/ml), ICTP (8.3 +/-
      1.3 ng/ml) and PIINP (3.5 +/- 0.5 ng/ml) levels were significantly lower (P <
      0.001) than those recorded in normal children (BGP 18.9 +/- 0.8 ng/ml, ICTP 14.4
      +/- 0.5 ng/ml and PIIINP 6.7 +/- 0.7 ng/ml). Total alkaline phosphatase (184.7 +/
      13.4 IU/l) and bone alkaline phosphatase (77.8 +/- 4.1 IU/l) levels were also
      significantly lower (P < 0.0001) than in controls (338.1 +/- 14.9 IU/l and 181.0
      +/- 7.8 IU/l, respectively). Serum BGP, ICTP and PIIINP levels were not
      significantly correlated with height velocity values. In adults with GHD, mean
      BGP levels (3.8 +/- 0.3 ng/ml) were significantly lower (P < 0.0001) than those
      recorded in normals (5.4 +/- 0.1 ng/ml). On the contrary, serum ICTP levels were
      similar to those found in controls (patients: 4.7 +/- 0.8 ng/ml vs normals: 4.1
      +/- 0.3 ng/ml), suggesting the presence of a normal resorption activity
      associated with a reduced osteoblastic function. This finding was also confirmed
      by the presence of reduced bone alkaline phosphatase levels (GHD: 44.9 +/- 6.9
      IU/I vs controls: 58.3 +/- 2.0 IU/I; P<0.02), while the less specific total
      alkaline phosphatase levels (119.5 +/- 14.8 IU/I) were similar to those recorded
      in normal subjects (122.3 +/- 4.0 IU/I). Serum PIIINP levels (3.7 +/- 0.6 ng/ml)
      were similar to those recorded in normals (3.2 +/- 0.2 ng/ml), suggesting that in
      adulthood the collagen turnover is not negatively influenced by the chronic GHD.
      No significant correlations were found between BGP/ICTP/PIIINP and IGF-I levels.
      In conclusion, our data show that in children with GHD the lack of GH insulin
      like growth factor-I (IGF-I) effects on bone and collagen turnover is associated
      with a significant reduction of bone turnover (low bone formation plus low bone
      resoRption) and collagen synthesis. On the contrary, adult GHD seems to exert
      less relevant effects on bone and collagen turnover, probably due to the fact
      that in adult life further hormones or local factors might partially counteract
      the negative consequences of chronic GH-IGF-I deficiency.

PMID- 8290429
TI  - Reporting ventilation-perfusion lung scintigraphy: impact on subsequent use of
      anticoagulation therapy.
AB  - Ventilation and perfusion lung scintigraphy is an established and safe
      noninvasive technique which has been used for nearly 30 years to establish the
      diagnosis of pulmonary embolism. Recently, in common with other diagnostic tests,
      there has arisen the need to reassess the effectiveness of this test in the
      clinical setting. A retrospective analysis of 244 patients undergoing ventilation
      perfusion lung scintigraphy was performed. A total of 203 case notes were
      available. It was found that the majority of reports (68.5%) were described as
      either high probability for the presence of pulmonary embolism or normal or low
      probability. A result of 'high probability' changed the clinical management of
      the patient in 28/46 (61%) of reported cases but in only 5/91 (5.5%) of patients
      reported as 'normal' or 'low probability'. During the study there were six
      deaths, five from other causes and one from pulmonary embolism; this patient died
      despite anticoagulation following a 'high probability' ventilation-perfusion lung
      scintigraphy. Ventilation-perfusion lung scintigraphy is a safe and effective
      noninvasive method to diagnose the presence of pulmonary embolism and a test
      which has a significant effect on patient management.

PMID- 8290431
TI  - Is the hot appendix really hot?
AB  - The skin temperature in the right and left iliac fossae was recorded in 100
      patients who were referred with a provisional diagnosis of acute appendicitis.
      This was not found to be a reliable aid in diagnosis of acute appendicitis nor an
      indicator to the need for surgery in patients with right iliac fossa pain.

PMID- 8290430
TI  - Prognostic factors in Wegener's granulomatosis.
AB  - We analysed data from 64 patients with Wegener's granulomatosis to determine
      predictor variables of outcome. The mean period of observation after the
      diagnosis had been established was 3.2 (range 0.1-11.2) years. At the time of
      diagnosis, 15 (23%) patients had only local symptoms. The disease was generalized
      to multiple organs in 49 (77%) patients. Renal biopsies were obtained in 33
      patients; 13 (39%) had extracapillary glomerulonephritis, which was the most
      common renal lesion. All but three patients received immunosuppressive therapy.
      At time of follow-up, 17 (27%) patients were in complete, and 26 (40%) in partial
      remission. We employed a Kaplan Meier analysis to identify predictor variables of
      outcome. Renal involvement, initial creatinine concentration, serum albumin or
      total protein concentration, leukocyte count and erythrocyturia proved to be
      predictor variables. These variables may be of value in guiding the intensity of
      treatment in patients with Wegener's granulomatosis.

PMID- 8290433
TI  - The Cochrane Collaboration: making the results of controlled trials properly
      accessible.

PMID- 8290432
TI  - A pharmacokinetic interaction between cimetidine or ranitidine and lornoxicam.
AB  - Cimetidine 400 mg twice daily significantly increased serum concentrations and
      reduced apparent oral clearance of lornoxicam 8 mg twice daily in 12 healthy
      volunteers. Ranitidine 150 mg twice daily produced no significant changes in
      lornoxicam pharmacokinetics.

PMID- 8290434
TI  - Bancroftian filarial pleural effusion.
AB  - This paper describes a case of filarial pleural effusion, the fifth such to be
      reported. Microfilariae of Wuchereria bancrofti were detected in the pleural
      fluid on cytological examination. There was a prompt and complete response to
      treatment with diethylcarbamazine. There were, however, no symptoms and signs of
      tropical pulmonary eosinophilia nor any peripheral eosinophilia.

PMID- 8290435
TI  - Transient regional osteoporosis presenting as a septic arthritis.
AB  - A 52 year old man developed a painful swollen left knee. Clinically there was an
      effusion and radiographs showed local osteoporosis. Sepsis was suspected but
      tests proved negative and the symptoms gradually settled. During the course of
      the following year he developed similar pain migrating from the left foot to the
      right knee then to the right foot. Investigations showed a right knee effusion
      and 'punctate' radiographic lucencies in the patellae thought to be erosions. A
      bone scan demonstrated increased uptake at all four sites and sepsis was once
      again suspected. Biopsies and culture proved negative and a computed tomographic
      scan confirmed that the lucencies were due to focal osteoporosis rather than
      erosions. This case of transient regional osteoporosis illustrates two unusual
      features of this condition which resulted in diagnostic difficulty with respect
      to sepsis.

PMID- 8290436
TI  - Focal myositis: an unusual cause of bilateral upper eyelid swellings.
AB  - Focal myositis is considered a rare self-limiting inflammatory swelling of
      skeletal muscle. Focal involvement of individual muscle or muscle groups with
      severe myopathic and inflammatory changes characterizes the histology. We report
      the development of progressive focal myositis in both upper eyelids of a 34 year
      old man that responded to immunosuppressive therapy.

PMID- 8290437
TI  - Candida lusitaniae causing fatal meningitis.
AB  - Fatal meningitis due to Candida lusitaniae in a 35 year old previously healthy
      man is described. C. lusitaniae is an opportunistic fungal pathogen reported
      infrequently in the English literature. This is the third case report of
      meningitis and the first fatal infection in an adult from Central India due to C.
      lusitaniae known to the authors.

PMID- 8290438
TI  - Bilateral anterior tibial compartment syndrome in association with
      hypothyroidism.
AB  - Local vascular and traumatic involvement are well-recognized causes of anterior
      tibial compartment syndrome (ATCS) terminating as myoneural ischaemia. However,
      in a large number of patients the cause of ATCS remains unidentified. We document
      the occurrence of bilateral ATCS in a patient of hypothyroidism, to our knowledge
      a previously unrecorded association.

PMID- 8290439
TI  - Carcinoma of the breast at the site of migrated pacemaker generators.
AB  - We report two patients in whom breast malignancy developed in the proximity of
      'migrated' pacemaker generators. These cases and the similar ones reported in the
      literature raise concerns whether this association is merely coincidental or
      whether the pacemaker generator is responsible for the occurrence in some
      inexplicable manner. We urge for a routine, careful examination in all patients
      with implanted pacemaker generators at follow-up visits. This would help in (a)
      timely detection of migration of the pacemaker generators and (b) earlier
      diagnosis of any mass developing close to the migrated generators.

PMID- 8290440
TI  - Type IV renal tubular acidosis and spironolactone therapy in the elderly.
AB  - Spironolactone therapy is a well-known cause of hyperkalaemia, but in susceptible
      patient, it may also be associated with metabolic acidosis. We report a case of
      severe renal tubular acidosis (Type IV) with life-threatening hyperkalaemia
      caused by spironolactone, and discuss the mechanisms by which this may occur.

PMID- 8290441
TI  - Age-related differences in simultaneous interarm blood pressure measurements.

PMID- 8290442
TI  - Aspirin and risk of fatal colon cancer.

PMID- 8290443
TI  - Fulminating streptococcal septicaemia.

PMID- 8290444
TI  - Hospital patients--are they active enough?

PMID- 8290445
TI  - Bactericidal effects of povidone-iodine solution to oral pathogenic bacteria in
      vitro.
AB  - Seven species of periodontal pathogenic bacteria (Bacteroides, gingivalis,
      Bacteroides intermedius, Bacteroides melaninogenicus, Fusobacterium nucleatum,
      Actinobacillus actinomycetemcomitans, Capnocytophaga spp., Eikenella corrodens)
      and two control species (Streptococcus intermedius, Pseudomonas aeruginosa) were
      selected in order to study the bactericidal effects of 10% povidone-iodine (PVP
      I) aqueous solution in vitro. The PVP-I solution was diluted to 10, 20, 50, 100,
      200, 400, 800, 1600, 3200, 6400 and 12800 x and contact times were 15, 30 and 60
      seconds. The strongest bactericidal effects on the seven periodontal pathogenic
      bacteria and two control bacteria were seen at a dilution of 400 x and a contact
      time of 15 seconds. Based on these findings, we advocate a 0.25% solution of 10%
      aqueous PVP-I for oral mucosa and periodontal pocket irrigation.

PMID- 8290446
TI  - Clinical significance of methicillin-sensitive and methicillin-resistant
      Staphylococcus aureus in UK hospitals and the relevance of povidone-iodine in
      their control.
AB  - This review summarizes the natural history, clinical relevance and basis of
      control of Staphylococcus aureus infection in UK hospitals, stressing the central
      role of asymptomatic carriage by patients and staff in persistence of this
      prolific and versatile nosocomial pathogen. The clinical relevance of methicillin
      resistant and methicillin-sensitive S. aureus (MRSA and MSSA) is considered in
      terms of prevalence and spectrum of invasive and toxigenic infections produced,
      correlated with host and parasite risk factors. An assessment is made of
      arguments why the acquisition of methicillin-resistance or multiple antibiotic
      resistance might justify more than conventional methods of containment and how
      the control policy is influenced by the expression of enhanced virulence and
      epidemicity. Guidelines for control of epidemic MRSA (EMRSA) are discussed with
      reference to justification, feasibility and efficacy. As elimination of carriage
      is crucial to the success of any rational control policy the relative merits of
      topical antibiotics and antiseptic agents are compared. The bacterial efficacy of
      povidone-iodine, chlorhexidine and mupirocin are evaluated as a basis for
      eradication of MRSA.

PMID- 8290447
TI  - Prevention and control of nosocomial infection caused by methicillin-resistant
      Staphylococcus aureus in a premature infant ward--preventive effect of a povidone
      iodine wipe of neonatal skin.
AB  - In early 1983 we experienced a small scale epidemic of Staphylococcus aureus
      coagulase type IV in the premature infants unit. Children had bacteraemia or
      impetigo. The microorganism was resistant to methicillin, erythromycin and
      lincomycin and was susceptible to tetracycline, chloramphenicol and cefmetazole.
      The results of coagulase typing and antimicrobial sensitivities indicated that
      these cases represented nosocomial infection with MRSA. The source and route of
      the infection were investigated, and measures were taken to prevent bacterial
      spread from carriers and to keep instruments and environments clean. As the
      source of infection was not identified, we tried wiping the body surface of the
      premature infants with a diluted IsodineR solution (10% povidone-iodine; 1:100
      dilution) in order to prevent colonization of the microorganism on the body
      surface. As a result, no additional MRSA infection occurred in the premature
      infant unit. During the subsequent 6 years of frequent surveys of carriers and
      wiping the appropriate body surface with diluted IsodineR solution we have had no
      recurrence of MRSA. None of the premature infants wiped with IsodineR solution
      showed any objective abnormalities, although laboratory testing disclosed an
      elevated blood iodine level and a transient mild reduction of T4 in some infants.

PMID- 8290448
TI  - Efficacy of intranasal application of povidone-iodine cream in eradicating nasal
      methicillin-resistant Staphylococcus aureus in neonatal intensive care unit
      (NICU) staff.
AB  - We investigated the staff in our neonatal intensive care unit (NICU) for the
      presence of methicillin-resistant Staphylococcus aureus (MRSA) in the nasal
      cavity, and then applied intranasal povidone-iodine cream to the physicians and
      nurses working on the unit. Prior to the application of povidone-iodine cream,
      the isolation rate of S. aureus from the nasal cavity was 30% for the physicians
      and nurses in contact with NICU patients (contact group), not significantly
      different from the 33.3% rate for other hospital staff (control group). The
      isolation rate for the contact group decreased to 10.5% after application of the
      cream. Although MRSA was not isolated from the nasal cavity of those in the
      control group, it was isolated from 13.3% of those of the contact group before
      application of the cream. Nasal MRSA disappeared after use of the cream. No
      adverse reactions or abnormalities in serum levels of thyroid hormone-related
      substances were observed in any of the subjects. These results indicated that the
      nasal application of povidone-iodine cream is safe and effective for eradicating
      MRSA in the nasal cavity.

PMID- 8290449
TI  - Epidemic methicillin-resistant Staphylococcus aureus (EMRSA): experience from a
      health district of central England over five years.
AB  - A series of outbreaks of EMRSA occurred in three hospitals of a Health District
      in the years 1986 and 1987, affecting 64 patients and 6 staff members. By the
      antibiotic sensitivity pattern (methicillin-resistance and resistance to many
      others) and phage typing, the organism resembled the epidemic strains involved in
      London outbreaks. In this series of outbreaks, different circumstances led to
      adaptation of different control measures with their cost implications. As failure
      with chlorhexidine was experienced, it was replaced with povidone-iodine for
      routine handwashing and topical application to patients in affected wards. Heavy
      environmental contamination involving mattress, bed, floor, table, chair, locker,
      television etc. was shown. Repeated failures of a phenolic disinfectant led to
      use of formaldehyde or a higher concentration of the phenolic disinfectant which
      caused side effects in staff members. Various anti-bacterial agents had been used
      in treating different conditions in different cases. Mupirocin was found to be
      the best agent in treating infections or colonization of superficial accessible
      sites. For non-accessible sites fusidic acid and rifampicin were found to be
      satisfactory. Continued surveillance in the District for three years after the
      last case did not detect re-emergence of EMRSA.

PMID- 8290450
TI  - Prevention of haemodialysis and peritoneal dialysis catheter related infection by
      topical povidone-iodine.
AB  - Catheter related sepsis, especially with staphylococci, is one of the most
      important complications of haemodialysis or peritoneal dialysis. In a
      prospective, randomized, open study of 129 haemodialysis patients, exit site
      infection and bacteraemia were significantly greater in the untreated group
      (18.2% each) than the group treated with povidone-iodine (PVP-I) ointment (4.8%
      each), P < 0.02. In nasal carriers of S. aureus, PVP-I resulted in 100% risk
      reduction of bacteraemia and exit site infection (P < 0.05) and 70% risk
      reduction of catheter tip infections (P < 0.05). Preliminary results of an on
      going randomized study in patients on intermittent peritoneal dialysis suggest,
      in the 69 patients so far studied, a reduced S. aureus infection rate in patients
      who received PVP-I ointment at the catheter exit site (2.9%) compared with the
      untreated group (8.8%) despite a higher nasal carriage rate in the PVP-I group.
      Statistical significance has not been demonstrated for these interim results and
      the study is continuing.

PMID- 8290451
TI  - Study of the antiseptic efficacy of a quick drying rubbing type povidone-iodine
      alcoholic disinfectant solution by the glove juice method.
AB  - The antiseptic efficacy of HAD Hand Wash (83% ethanol containing 0.5% povidone
      iodine) was investigated by the glove-juice method in 29 cases amongst staff
      members of our university. The number of viable bacteria on the hands and fingers
      was counted three times, and the mean of these counts was used as the baseline
      value for each subject. The number of viable bacteria on both hands was the same
      prior to disinfection. After the hands were disinfected by rubbing with 3 ml of
      HAD Hand Wash until it dried, the subjects put on sterile gloves. The number of
      viable bacteria was counted on the right hand of all the subjects immediately
      after disinfection. The number of viable bacteria on the left hand was counted in
      8 subjects 30 minutes after disinfection, and in 7 subjects each 1, 2 and 4 hours
      after disinfection. The bacteria were identified by subculture. The ratio of
      bacteria sterilized (bacterial reduction rate) was 75.4% immediately after
      disinfection, and 69.0%, 71.9%, 35.8% and 27.6% at 30 minutes, 1 hour, 2 hours
      and 4 hours, respectively. All of the bacteria detected were Gram-positive
      bacteria that were native to the sebaceous glands, sweat glands or skin surface;
      i.e. Staphylococcus, Micrococcus, Bacillus, and Streptococcus. The frequency of
      detection of Staphylococcus warneri was the highest before disinfection, followed
      by Staphylococcus epidermidis and Staphylococcus hominis, in that order. After
      disinfection, all these species showed a marked decrease in the number of
      bacteria. Micrococcus remained in half the subjects, while other species remained
      in less than one third of the subjects.

PMID- 8290452
TI  - The antiseptic effect of a quick drying rubbing type povidone-iodine alcoholic
      disinfectant solution.
AB  - A quick drying rubbing type disinfectant of non-water non-towel type is an
      antiseptic method suitable for practical use in intensive care units where
      emergency situations are common. We determined the antiseptic efficacy and safety
      of a quick drying rubbing type povidone-iodine alcoholic disinfectant solution
      (HAD Hand Wash) in comparison with benzalkonium chloride alcoholic lotion. The
      bacterial reduction rate obtained by hand washing with a single 3 ml application
      was 93.8% for HAD Hand Wash and 94.1% for benzalkonium chloride alcoholic lotion.
      Thus, excellent antiseptic efficacy was obtained with both disinfectants.
      Roughening of hand skin which appeared in association with HAD Hand Wash solution
      was transient and mild in nature in all of the cases, indicating the high safety
      of this disinfectant. It is justified to say from these findings that HAD Hand
      Wash is useful as a hand and finger disinfectant.

PMID- 8290453
TI  - Efficacy and safety of a quick drying rubbing type povidone-iodine alcoholic
      disinfectant solution.
AB  - The efficacy and safety of a quick drying rubbing type disinfectant (HAD Hand
      Wash) composed of a povidone-iodine (PVP-I) and ethanol were evaluated in the
      disinfection of transient skin flora on fingers of 30 medical staff of our
      department. Three millilitres of HAD solution was rubbed onto the hands for three
      minutes several times a day over a four week period. Bacteriological effects were
      evaluated twice, on the first day and after four weeks, by the palm stamp method.
      The rate of colonies sterilized (bacterial reduction rate) after the use of HAD
      Hand Wash was 86.9 +/- 21.2% (mean +/- SD) on the first measurement, and 91.5% +/
      12.8% at four weeks. Staphylococcus epidermidis was isolated most frequently and
      this was eradicated in 83.3% of subjects, the bacterial reduction rate 99.7%.
      Staphylococcus aureus was originally isolated in 14 subjects and was eradicated
      in 13; the bacterial colony reduction rate was 99.9% showing high antiseptic
      efficacy. Although the bacterial reduction rate for Bacillus sp. was a rather
      low, 75.8-100%, this result was not considered problematic from the clinical
      standpoint. There were no side effects like chapping in spite of an average 104
      applications of HAD Hand Wash during the 4-week test period. From these results,
      HAD Hand Wash was considered highly effective and safe.

PMID- 8290454
TI  - Evaluation of the disinfectant effect of a quick drying rubbing type povidone
      iodine alcoholic solution by the glove juice method.
AB  - The antiseptic effect of povidone-iodine alcoholic solution (HAD Hand Wash), a
      newly developed quick drying rubbing type disinfectant, was evaluated in 40
      subjects. Samples of hand bacteria were collected by the glove juice method. The
      bacteria were incubated, and a cell count was performed. Disinfection was carried
      out by rubbing 3 ml of HAD Hand Wash carefully on to the skin of the subjects'
      hands. The efficacy of the solution was evaluated by computing the bacterial
      reduction rates as compared to the pre-disinfection bacterial count after
      disinfecting once and three times. The bacterial cell count was significantly
      reduced from the pre-disinfection count for one hour after disinfecting once and
      for two hours after disinfecting three times. In addition, the bacterial
      reduction rate after disinfecting three times remained superior to that after
      disinfecting once over a period of two hours. We concluded that disinfecting once
      with HAD Hand Wash is sufficient for routine hygienic hand washing, while
      disinfecting three times is desirable when, as with surgical hand washing, the
      strictest antisepsis is required. HAD Hand Wash produced no adverse side effects.

PMID- 8290455
TI  - Effect of treatment with povidone-iodine vaginal pessaries on thyroid function.
AB  - Twenty women suffering from candidal, trichomonal and non-specific vaginitis were
      treated by povidone-iodine vaginal pessaries twice daily for 14 days. Blood
      samples were obtained from patients before and 7 and 14 days after treatment for
      the determination of serum thyroid stimulating hormone, total thyroxine, free
      thyroxine, total triiodothyronine, free triiodothyronine, reverse
      triiodothyronine, thyroxine binding globulin and thyroglobulin by the
      corresponding specific 125I radioimmunoassay. In addition serum protein bound
      iodine was determined by a spectrophotometric method. Post-treatment values of
      these parameters after 7 and 14 days were not significantly different from the
      corresponding pretreatment values. Vaginal discharge disappeared in 82% of
      patients; with partial improvement in the remaining 18%. No clinical side effects
      and no clinical evidence of thyroid disorder were found in any of the women.
      These results indicate that treatment with povidone-iodine vaginal pessaries is
      effective in the treatment of different forms of vaginitis and their daily use in
      euthyroid, non-pregnant women is safe and has no effect on thyroid function.

PMID- 8290456
TI  - Review presentation on povidone-iodine antisepsis in the oral cavity.
AB  - Due to the great number of different micro-organisms present, the oral cavity is
      an important source of infection. Infections caused by these micro-organisms can
      occur as local infections of the oral mucous membrane, local infections of the
      soft tissues or the bones following surgical intervention, or endocarditis due to
      bacteraemia following dental surgery. In the therapy of periodontal diseases, the
      application of antiseptic solutions is indicated to inhibit or reduce plaque
      accumulation. Povidone-iodine (PVP-I) solution will reduce inflammation and the
      progression of periodontal disease. The application of antiseptics in the oral
      mucous membrane is also indicated to prevent wound infections following surgical
      intervention in patients with leukaemia, AIDS, immunosuppressant therapy and
      patients undergoing anti-neoplastic radiation or chemotherapy. Some trials on the
      antibacterial efficacy of PVP-I in vivo showed reduction factors of log 2-3. PVP
      I may therefore be recommended as an oral antiseptic. The irrigation of the
      gingival sulcus with an antiseptic solution is a useful complement to antibiotic
      prophylaxis in patients at risk of bacterial endocarditis. Many trials on the
      effectiveness of PVP-I on dental extraction bacteraemia have shown a significant
      benefit in the active group in comparison with the control group.

PMID- 8290457
TI  - Genital antisepsis--test methodology and efficacy of povidone-iodine.
AB  - Indications for antiseptic prophylaxis include use prior to urinary
      catheterization and other transurethral instrumentations, diagnostic or
      therapeutic instrumentation of the cavum uteri, and operations on the external
      genitalia and the vagina. Indications for antiseptic therapy include treatment of
      wounds and of infections of the genital tract and also include treatment of the
      vaginas of pregnant women to prevent infection in the newborn. For prophylactic
      antisepsis the aim is the optimal reduction of potentially pathogenic
      microorganisms. In some fields of application, e.g. before urinary
      catheterization, an immediate effect on the mucous membrane is required, but on
      other occasions, such as transvaginal operations, an additional sustained effect
      is desired. Testing the efficacy of mucous membrane antiseptics, especially for
      the genital tract, necessitates the establishment of standardized test methods.
      The variability in vaginal flora at various ages makes it reasonable to study
      women aged 20-50 years. Studies presented in this paper indicate that
      microorganism sampling using a cotton swab moistened with neutralizing fluid can
      be favoured compared to using a rinsing technique and that anaerobic culture
      techniques enable the measurement of the high reduction factors achieved by very
      efficient antiseptic procedures. Test methods validated for hand disinfectants
      are used for calculations and statistical evaluation. The antimicrobial efficacy
      of six vaginal antiseptic procedures were compared in patients prior to vaginal
      surgery. Three minutes after treatment, the highest mean reduction (log RF) of
      the normal vaginal flora as well as of potentially pathogenic microorganisms was
      obtained by povidone-iodine solution undiluted and povidone-iodine solution 1:10
      (log RF 3.60 and 2.68, respectively). Out of three detergents with antimicrobial
      efficacy, octenidine 0.1% was the most effective preparation (log RF 2.32).
      Chlorhexidine 0.1%, hexetidine 0.1% and chlorhexidine 0.05% led to lower
      reduction factors (log RF 1.80, 1.62 and 1.02, respectively). After 30 minutes
      the log reduction factors were approximating each other in nearly all procedures
      (log RF 2.79-3.25) except the log RF derived from the procedure performed using
      chlorhexidine 0.05% (log RF 2.07). Povidone-iodine solutions seem to be the
      method of choice for mucous membrane antisepsis where an immediate effect is
      required. If a long period of action is needed all procedures examined, except
      chlorhexidine 0.05%, are acceptable.

PMID- 8290458
TI  - Study on the usefulness of povidone-iodine obstetric cream with special reference
      to the effect on the thyroid functions of mothers and the newborn.
AB  - The effect of povidone-iodine obstetric cream (OAD cream) on the thyroid
      functions of mothers and the newborn was investigated in 56 patients. Effects on
      labour and on the neonatal course of the newborn were also studied. OAD cream was
      used for disinfection of the vulva and vagina during prenatal obstetric
      examinations (1-10 times) and at parturition. Bacteriological specimens were
      obtained before and after use of the OAD cream, and the total iodine, thyroid
      stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels were
      measured in the maternal blood and umbilical cord blood. The overall bacterial
      eradication rate for the vulva was 74.7% although the eradication rate for
      coagulase negative staphylococci was low (23.1%). The overall bacterial
      eradication rate for the vagina was 56.1% although the eradication rates for
      Candida albicans and Lactobacillus spp. were low (9.1% and 29.4% respectively).
      There was no significant difference in the types of delivery or complications of
      labour and delivery between the group treated with OAD cream and the control
      group, but the duration of labour was prolonged in the former group. There were
      no malformations among the newborn, and no difference between the group treated
      with OAD cream and the control group in regard to body weight and length of the
      newborn at birth, Apgar score, postnatal gain in body weight, or bilirubin level.
      The maternal blood levels of total iodine, TSH, and T4 were within the normal
      ranges both during pregnancy and at delivery, but the level of T3 was slightly
      elevated at delivery. The umbilical cord blood levels of the total iodine, TSH,
      and T4 were within normal ranges both during pregnancy and at delivery, but the
      level of T3 was somewhat elevated. At age six days, the T4 level was normal in
      all the newborn. TSH was higher than 15 microU/ml in two newborns, but returned
      to normal levels three week later.

PMID- 8290459
TI  - The efficacy of povidone-iodine pessaries in a short, low-dose treatment regime
      on candidal, trichomonal and non-specific vaginitis.
AB  - Povidone-iodine pessaries (Betadine vaginal pessaries) containing 200 mg of
      povidone-iodine (PVP-I) in a water soluble base, are a widely used gynaecological
      preparation for treatment of vaginitis. We conducted a study on PVP-I pessaries
      at the reduced dose of one pessary daily for 7 days to suit conditions in Macau
      where patients are eager for a simple, short treatment course with confirmed
      clinical efficacy benefiting their professional and household essential
      requirements. Thirty-eight cases were selected for this particular clinical
      trial. These consisted of housewives, factory workers and professional girls (a
      sexually high risk group) who were suffering from vaginitis and complaining of
      vaginal discharge and irritation due to trichomonas, candida or non-specific
      vaginitis. After routine examination, including the collection of samples for
      microbiology, patients were treated with PVP-I pessaries 200 mg once a day for 7
      days. The second microbiology samples were collected after the 7 day treatment
      period. Among the 38 cases, we had 30 cases with a complete record to allow us to
      make a summary and analysis of the trial. There were 14 cases of vaginitis due to
      yeasts and fungi infection, 3 cases of protozoa (trichomonas), and 13 cases due
      to non-specific pathogenic infections. 73.3% of cases had a complete symptomatic
      and microbiological cure and a further 16.7% had a microbiological cure with a
      good improvement in symptoms. No complications or side effects were found in the
      7 days consecutive treatment course and inflammation quickly subsided during the
      course of treatment. PVP-I pessaries, used once daily for 7 days, seem to be an
      ideal treatment for cases who are likely to be unable to follow a longer
      treatment course.

PMID- 8290460
TI  - In vitro efficacy of povidone-iodine solution and cream against methicillin
      resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has emerged worldwide as a
      significant and difficult-to-treat source of nosocomial infection, emphasizing
      the ever-present need for reliable and effective antisepsis. Betadine Solution
      (10% povidone-iodine; PVP-I) and Betadine Cream (5% povidone-iodine) are broad
      spectrum microbicides widely used for topical cleansing, wound treatment, and
      antisepsis. There have been no reports of bacterial resistance to Betadine
      preparations. In the present study in vitro killing times were determined for PVP
      I solution and PVP-I cream against five hospital isolates of MRSA and one
      methicillin-sensitive strain (MSSA). Isolates were incubated for 24 hours in
      trypticase soy broth and 0.5 ml, containing 10(6)-10(7)/ml bacteria, was then
      removed and added to each test agent containing PVP-I. At intervals of 30
      seconds, 1 min, 2 min, 3 min, 5 min, 10 min, and 15 min, 10 microliters aliquots
      were removed and added to 10 ml of culture broth containing 0.1% sodium
      thiosulphate, the neutralizing agent for PVP-I. After neutralization the samples
      were incubated for 48 hours and then observed for growth (turbidity) or its
      absence. PVP-I solution was effective against all isolates, killing each strain
      within 30 seconds. PVP-I cream killed four of the MRSA isolates within 30
      seconds, and required a 2-3 minute killing time for one strain of MRSA and the
      strain of MSSA. These results are supported by four published in vitro studies
      which show that PVP-I is highly effective in killing MRSA. In addition, each
      study shows that PVP-I is more effective than chlorhexidine against MRSA.

PMID- 8290461
TI  - Comparison of bactericidal activities of various disinfectants against
      methicillin-sensitive Staphylococcus aureus and methicillin-resistant
      Staphylococcus aureus.
AB  - Various disinfectants were compared in terms of the duration of bactericidal
      activity against methicillin-sensitive Staphylococcus aureus (MSSA), and
      methicillin-resistant Staphylococcus aureus (MRSA), among S. aureus isolated in
      our hospital. Strains of S. aureus which showed minimum inhibitory concentrations
      of cloxacillin of less than 1.56 micrograms/ml and of 3.13 micrograms/ml or
      higher were designated MSSA and MRSA respectively. There was no difference in
      sensitivity to disinfectants between MSSA and MRSA. There was a great variation
      in the duration of bactericidal activity of chlorhexidine gluconate against these
      species with the majority requiring contact times of between 2 minutes and over
      20 minutes. All strains except for one strain of MRSA were killed within 20
      seconds after disinfection with benzalkonium chloride. All strains were killed
      within 20 seconds after disinfection with alkyldiaminoethylglycine hydrochloride
      or povidone-iodine.

PMID- 8290462
TI  - Review of disinfectant susceptibility of bacteria isolated in hospital to
      commonly used disinfectants.
AB  - The susceptibility of clinical isolates and indigenous bacteria to commonly used
      disinfectants was investigated during different time periods. Among the clinical
      isolates tested during Period I (August 1985-July 1986, 6 genera, 9 species, 353
      strains) there were many resistant strains not killed within a short period of
      time by the recommended concentration of chlorhexidine gluconate (CHG) or
      benzalkonium chloride (BAC). During Period II (October 1987-May 1988, 6 genera, 9
      species, 152 strains), however, a reduction in the number of strains resistant to
      these disinfectants was observed. The use of the broad spectrum disinfectant
      povidone-iodine (PVP-I) increased between those two time periods. With regard to
      the susceptibility of indigenous bacteria, tests were carried out on bacteria
      isolated from sinks and physicians' hands in the gastroenterology division of the
      Departments of Internal Medicine and Surgery at the hospital. During Phase I
      (April-June 1987), strains of Pseudomonas and Serratia resistant to CHG and BAC
      were isolated from sinks, while the same strains of Serratia were also isolated
      from physicians' hands. During Phase II (March-May 1988), however, no resistant
      strains were isolated. A comparison of the consumption of disinfectants during
      the two phases revealed that a greater amount of CHG was consumed during Phase I,
      while a greater amount of PVP-I was consumed during Phase II. There was a strong
      indication, therefore, that bacteria resistant to CHG and BAC decrease with the
      increased use of PVP-I.

PMID- 8290463
TI  - Action of povidone-iodine against methicillin-sensitive and -resistant cultures
      of Staphylococcus aureus.
AB  - Forty clinical isolates of methicillin-resistant and methicillin-sensitive
      Staphylococcus aureus were studied for their susceptibility to povidone-iodine
      (available iodine 11%) under a variety of conditions. The cultures varied in
      properties, notably in their sensitivity to other therapeutic agents. No
      differences were observed between the resistant and sensitive cultures in
      destruction by povidone-iodine. When bactericidal activity occurred, > 99% of the
      bacterial cells were lethally damaged within 10 seconds of exposure to povidone
      iodine. The bacterial cells that had been washed and resuspended thrice in
      distilled water were most susceptible, with as little as 1 x 10(-16) G (2.36 x
      10(5) atoms) of iodine being required to destroy one bacterial cell. Attempts
      were made to select variants resistant to iodine from the surviving minority
      population in such experiments. These experiments failed to select resistance,
      and it is concluded that any apparent variation in vulnerability to povidone
      iodine results from aggregation of the bacteria and differences in penetration of
      povidone-iodine. Substances were studied for their ability to inactivate povidone
      iodine. The most potent agents were the free sulphur-containing amino acids,
      cysteine and methionine. These are present in high concentrations in nutrient
      broth and most other culture media. This explains the reports of 'pseudo
      resistance' to povidone-iodine in certain laboratory experiments. Suggestions are
      made for the optimum use and formulation of povidone-iodine.

PMID- 8290464
TI  - Review of the use of povidone-iodine (PVP-I) in the treatment of burns.
AB  - Local infection and burn wound sepsis are one of the most severe problems in the
      treatment of thermally injured patients. Early surgical treatment and the use of
      topical antiseptics led to a decrease in the infection rate and significantly
      improved the survival rate of burns patients within the last twenty-five years.
      Many antiseptics are used in the treatment of burns. Silver nitrate, silver
      sulphadiazine, sulfamylon and povidone-iodine (PVP-I) are the most common
      substances used worldwide in burn care facilities. Clinical studies demonstrate
      that treatment with PVP-I is the most effective against bacterial and fungal
      infection. Several methodological problems however arise from direct comparison
      between these antiseptics, and local and systemic adverse effects can make the
      right choice difficult. Some case reports documented possible side effects in the
      treatment of patients with PVP-I, leading to general concerns about this
      treatment. Absorption of iodine and possible changes in thyroid hormones are well
      known, but evaluation of the clinical consequences is controversial. Reports of
      severe metabolic acidosis and renal insufficiency with lethal results have
      condemned the use of PVP-I in the treatment of extensive burns. The case reports,
      however, dealt with patients suffering from general morbidity and sepsis and
      therefore these single reports may not be generally valid. Local treatment of
      burns may cause further problems. The beneficial effect of a decrease of
      bacterial counts in deeper tissue may be confounded by other effects delaying
      wound healing, as shown in some experimental studies. Controlled clinical
      investigations on burn patients however are still missing. The paper will discuss
      these topics in detail referring to the treatment of burns with PVP-I. It is
      based on a critical review of the literature and the author's own experience in
      burns therapy.

PMID- 8290465
TI  - Evaluation of povidone-iodine alcoholic solution for operative site disinfection.
AB  - A clinical investigation of povidone-iodine alcoholic solution on disinfectant
      efficacy at the operative site was carried out in comparison with poloxamer
      iodine alcoholic solution and povidone-iodine aqueous solution. Bacterial samples
      obtained by the cylinder scrub method from 10 cm2 of abdominal skin pre- and post
      disinfection were filtered using a millipore membrane and cultured aerobically at
      37 degrees C for 48 hours. The antimicrobial efficacy of each product was
      expressed as the logarithmic reduction value (reduction factor) in resident
      bacterial counts. Significantly higher reduction factors (RF) of the total
      resident bacteria were obtained with povidone-iodine ethanol solution (RF 2.02)
      than with povidone-iodine aqueous solution (RF 1.17). No adverse reaction was
      observed with either preparation during the study period. It is concluded that
      povidone-iodine ethanol solution is a reasonable and effective antibacterial
      agent for pre-operative skin preparation.

PMID- 8290466
TI  - An appraisal of povidone-iodine and wound healing.
AB  - Infection is one of the most frequent complications of wound healing despite the
      use of antibiotics and modern sterile technique; it accounts for considerable
      patient morbidity, discomfort, and prolonged hospitalization, and it must be
      avoided to permit proper healing. For this purpose, topical antiseptics have been
      employed for several years. Among these povidone-iodine formulations
      (polyvinylpyrrolidone iodine; PVP-I; e.g., Betadine preparations), which consist
      of a water-soluble complex of elemental iodine and a synthetic polymer, have a
      broad antimicrobial spectrum, and have not been reported to develop bacterial
      resistance. Because some reports have suggested that PVP-I may interfere with
      wound healing, a critical review of studies concerning PVP-I and wound healing
      was undertaken, with emphasis placed on in vivo models that replicate, as closely
      as possible, human wound healing. Four forms of PVP-I were evaluated: PVP-I
      solution, PVP-I skin cleanser/surgical scrub, PVP-I ointment, and PVP-I cream.
      PVP-I solutions had virtually no deleterious effect on wound healing: application
      of 10% PVP-I solution to rat, guinea pig, rabbit, or pig wounds did not reduce
      wound tensile strength or delay re-epithelialization. In three human studies, no
      significant difference in healing was observed for 1%, 5% or 10% PVP-I solution
      except for a slight delay during the first 24 hours after the application of 5%
      PVP-I solution in one study; healing was normal by 72 hours. PVP-I skin
      cleansers/surgical scrubs contain ammonium nonoxynol-4-sulphate and lauramide DEA
      which, like all detergents, can cause tissue damage and delay healing. This was
      substantiated by a guinea pig study in which the detergent component but no the
      antiseptic produced these effects. In human trials, no damage occurred if
      cleansing of the wound with PVP-I skin cleansers/surgical scrubs was followed by
      saline irrigation. These results are consistent with recommendations for promptly
      rinsing the wound with water to remove the detergent if detergent-containing PVP
      I preparations are used for wound care. PVP-I ointment (10%) delayed wound
      closure inn rats during the fourth through tenth days post-treatment; however,
      during the next two weeks, healing was accelerated, and by day 24, healing was
      equal to the controls. No delays occurred when pigs or rabbits were tested. In
      human wounds, no delays occurred in healing, even when gel-type occlusive
      dressings were added to the wounds; in fact, bandage-wearing time was shortened
      in those patients treated with PVP-I ointment. PVP-I cream (5%) was also studied
      in humans; the cream formulation appeared to decrease healing time. Based on
      these studies, it can be concluded that povidone-iodine preparations do not have
      a deleterious effect on wound healing.

PMID- 8290467
TI  - In vitro evaluation of dexamethasone-beta-D-glucuronide for colon-specific drug
      delivery.
AB  - Dexamethasone-beta-D-glucuronide is a potential prodrug for colonic delivery of
      the antiinflammatory corticosteroid dexamethasone. Previous studies [T. R. Tozer
      et al., Pharm. Res. 8:445-454 (1991)] indicated that a glucoside prodrug of
      dexamethasone was susceptible to hydrolysis in the upper gastrointestinal tract.
      Resistance of dexamethasone-beta-D-glucuronide to hydrolysis in the upper
      gastrointestinal tract was therefore assessed. Conventional, germfree, and
      colitic rats were used to examine enzyme levels along the gastrointestinal tract
      to compare the stability of two model substrates (p-nitrophenyl-beta-D-glucoside
      and -beta-D-glucuronide) and to evaluate the prodrug dexamethasone-beta-D
      glucuronide. Hydrolytic activity was examined in the luminal contents, mucosa,
      and underlying muscle/connective tissues in all three types of rats. Enzymatic
      activity (beta-D-glucosidase and beta-D-glucuronidase) was greatest in the lumen
      of cecum and colon of conventional rats. In contrast, germ-free rats exhibited
      relatively high levels of beta-D-glucosidase activity (about 80% of total
      activity in the conventional rats) in the proximal small intestine (PSI) and the
      distal small intestine (DSI). Rats with induced colitis (acetic acid) showed
      reduced levels of luminal beta-D-glucuronidase activity in the large intestine;
      however, beta-D-glucosidase activity was relatively unchanged relative to that of
      the conventional rat. Mucosal beta-D-glucuronidase activity was significantly
      lower in the colitic rats compared with that in the conventional animals. Despite
      reduced luminal levels of beta-D-glucuronidase activity in the colitic rats,
      there was still a sharp gradient of activity between the small and the large
      intestines. Permeability of the glucoside and glucuronide prodrugs of
      dexamethasone through a monolayer of Caco-2 cells was relatively low compared to
      that of dexamethasone. The results indicate that dexamethasone-beta-D-glucuronide
      should be relatively stable and poorly absorbed in the upper gastrointestinal
      tract. Once the compound reaches the large intestine, it should be hydrolyzed to
      dexamethasone and glucuronic acid. Specificity of colonic delivery in humans
      should be even greater due to lower levels of beta-D-glucuronidase activity in
      the small intestine compared with that in the laboratory rat.

PMID- 8290468
TI  - The kinetics of relaxin oxidation by hydrogen peroxide.
AB  - In this study, hydrogen peroxide was used to study the oxidation of rhRlx under
      various conditions. Oxidation of rhRlx occurred at both of the two methionines on
      the B chain, Met B(4) and Met B(25), as expected from the three-dimensional
      structure of the molecule, which shows that these two residues are located on the
      surface of the molecule and exposed to solvent. The reaction produced three
      different oxidized forms of rhRlx containing either Met B(4) sulfoxide, Met B(25)
      sulfoxide, or both residues oxidized. The corresponding sulfone was not formed
      under these conditions. The oxidation at the two methionines proceeded
      independently from each other but Met B(25) was oxidized at a significantly
      faster rate than Met B(4). The fact that the rate of oxidation at Met B(25) was
      identical to the rate of oxidation of free methionine and that of two model
      peptides mimicking the residues around Met B(4) and Met B(25) suggests that the
      lower reactivity at Met B(4) was due to steric hindrance, and at least in this
      case, neighboring groups do not influence the oxidation kinetics of methionine
      residues. The reaction was independent of pH, ionic strength, and buffer
      concentration in the range studied. The enthalpy of activation for the reaction
      was approximately 10-14 kcal mol-1, with an entropy of activation of the order of
      -30 cal K-1 mol-1. These data are consistent with previously published mechanisms
      for organic sulfide oxidation by alkyl hydroperoxides.

PMID- 8290469
TI  - Chemical pathways of peptide degradation. V. Ascorbic acid promotes rather than
      inhibits the oxidation of methionine to methionine sulfoxide in small model
      peptides.
AB  - The effect of primary structure and external conditions on the oxidation of
      methionine to methionine sulfoxide by the ascorbate/Fe3+ system was studied in
      small model peptides. Degradation kinetics and yield of sulfoxide formation were
      dependent on the concentration of ascorbate and H+, with a maximum rate observed
      at pH 6-7. Phosphate buffer significantly accelerated the peptide degradation
      compared to Tris, HEPES, and MOPS buffers; however, the formation of sulfoxide
      was low. The oxidation could not be inhibited by the addition of EDTA. Other side
      products besides sulfoxide were observed, indicating the existence of various
      other pathways. The influence of methionine location at the C terminus, at the N
      terminus, and in the middle of the sequence was investigated. The presence of
      histidine in the sequence markedly increased the degradation rate as well as the
      sulfoxide production. The histidine catalysis of methionine oxidation occurred
      intramolecularly with a maximum enhancement of the oxidation rate and sulfoxide
      production when one residue was placed between the histidine and the methionine
      residue.

PMID- 8290470
TI  - Determination of acrolein in urine by liquid chromatography and fluorescence
      detection of its quinoline derivative.
AB  - We describe an assay for acrolein in urine, employing derivatization with m
      aminophenol in the presence of ferrous sulfate solution in sulfuric acid. The
      derivative (7-OH quinoline; DER) and the internal standard (quinine-bisulfate;
      IS) were separated on a 10-micron particle, 8 mm x 10-cm C18 cartridge in
      conjunction with a radial compression system using a mixture of 0.05 M dibasic
      ammonium phosphate solution (pH 2.5):acetonitrile:methanol (92:6:2) at a flow
      rate of 3 mL/min as a mobile phase. The effluent was monitored fluorometrically
      at excitation and emission wavelengths of 360 and 495 nm, respectively. The
      retention times of DER and IS under these conditions were 4.3 and 26 min,
      respectively, and no interference in the assay from any endogenous substance or
      other concomitantly used drug was observed. The assay was highly linear (r >
      0.994) in the range 1-20 micrograms/mL of acrolein in urine (CV at different
      concentrations, < or = 7.9%). This method can serve to monitor acrolein
      pharmacokinetics in patients.

PMID- 8290471
TI  - Sterilization of liposomes by heat treatment.
AB  - Autoclaving of liposomes composed of egg phospholipids or saturated
      phospholipids, the latter sometimes combined with cholesterol, was performed in
      an isotonic acetate buffer (pH 4.0) or Hepes buffer (pH 7.4). After a standard
      autoclaving cycle (15 min, 121 degrees C), no change could be observed in pH,
      size, and extent of oxidation. Dependent on the experimental conditions, a minor
      or substantial increase in the fraction of hydrolyzed phospholipids was found.
      After a sterilization cycle, pronounced leakage was found for a water-soluble,
      encapsulated compound (calcein) and for an amphiphilic compound (doxorubicin).
      Lipophilic, liposome bilayer-associated compounds [N-trifluoroacetyldoxorubicin
      14-valerate (AD-32) and alpha-tocopherol] remained in the liposomes after
      autoclaving. However, substantial degradation of AD-32 was observed. Under proper
      conditions liposomes without or with thermostable, lipophilic drugs can be
      sterilized by autoclaving. However, the hydrolysis of phospholipids can pose a
      problem, as hydrolysis kinetics depend on the pH used. In the chosen
      circumstances the autoclaving cycle caused massive loss of hydrophilic,
      nonbilayer interacting compounds; under those conditions "free" drug removal or
      drug encapsulation should be performed after the autoclaving step.

PMID- 8290472
TI  - Evaluation of Preflo modified starches as new direct compression excipients. I.
      Tabletting characteristics.
AB  - This investigation evaluated some new (Preflo) and existing commercially
      available (Starch 1500, Star Tab) modified starches as direct compression
      excipients. Preflo corn starches (CH-10, CH-20, CH-30) and Preflo potato starches
      (P-250, PI-10, PJ-20) were evaluated and compared with respect to their
      pharmaceutical properties such as particle size, density, flowability,
      friability, and compression properties. Preflo starches showed a high bulk
      density and good flowability. Preflo corn starches and Star Tab formed harder
      tablets than Preflo potato starches and Starch 1500. Data from the Athy-Heckel
      plots indicated that the Preflo starches are soft materials and, unlike Starch
      1500, undergo plastic deformation. Tablets containing acetaminophen were also
      compressed with the starches and disintegration and dissolution studies were
      conducted. Starch 1500 tablets disintegrated in 3.5 min, whereas none of the
      Preflo starch tablets disintegrated in 30 min. While complete acetaminophen
      release occurred in 25 min from Starch 1500 tablets, the drug dissolution time
      from Preflo starch tablets varied from 4 to 12 hr, indicating a potential use for
      some of these starches in solid oral modified-release dosage forms.

PMID- 8290474
TI  - Recovery and elimination of the biotherapeutic agent, Saccharomyces boulardii, in
      healthy human volunteers.
AB  - Saccharomyces boulardii (Sb) is a nonpathogenic yeast used to treat intestinal
      illnesses such as pseudomembranous colitis and antibiotic associated diarrhea.
      The behavior of this biotherapeutic agent in humans was determined (1) in
      investigating the effect of dose on the steady-state level and recovery and (2)
      in quantitating the effect of ampicillin on the recovery and elimination profile.
      As the Sb dose increased, the mean steady-state concentration of Sb increased
      significantly. The percentage recovery was dose independent. When a single Sb
      dose was administered 24 hr after beginning a course of ampicillin, there was a
      significant increase (P < 0.01) in both the area under the concentration versus
      time curve and the maximum fecal concentration compared to values obtained
      without ampicillin. Ampicillin increased steady-state recovery of the drug about
      twofold (P < 0.05) and steady-state levels about 2.4 times (P < 0.01). These
      studies have shown that there is a relationship between the dose and the amount
      of Sb recovered and that perturbation of the GI flora by ampicillin increases
      steady-state levels of Sb.

PMID- 8290473
TI  - Pharmacokinetic analysis and cellular distribution of the anti-HIV compound
      succinylated human serum albumin (Suc-HSA) in vivo and in the isolated perfused
      rat liver.
AB  - After intravenous injection of a low dose (25 micrograms/kg) in rats, the anti
      HIV-1 compound succinylated human serum albumin (Suc-HSA) is taken up mainly in
      the liver and spleen and is proteolytically degraded. Ten minutes after injection
      of 125I-Suc-HSA, 72 and 14% of the dose were found in the liver and spleen,
      respectively. With immunohistochemistry we demonstrated that in both organs, Suc
      HSA was specifically endocytosed in endothelial cells. In the isolated perfused
      rat liver preparation, liver uptake was shown to be saturable, with a Km of 2.9
      10(-8) M and a Vmax of 2.4 micrograms/min/100 g body weight. The apparent Km and
      Vmax in vivo were 2.2 10(-7) M and 10.3 micrograms/min/100 g, respectively.
      Uptake in liver and spleen was inhibited by preadministration of an excess of
      formaldehyde-treated albumin and with polyinosinic acid, indicating the
      involvement of the scavenger receptor, as anticipated for such polyanionic
      compounds. Suc-HSA is not absorbed intact from the colon and the ileum. After
      injecting (i.v.) rats with a high dose of Suc-HSA (10 mg/kg), the elimination
      t1/2 was 3 hr, and therefore, sustained plasma levels above the concentration
      needed for in vitro anti-HIV-1 activity can be achieved.

PMID- 8290476
TI  - Formulation, in vitro dissolution, and ocular bioavailability of high- and low
      melting phenylephrine oxazolidines.
AB  - The in vitro dissolution and the relative ocular bioavailability of high- and low
      melting phenylephrine oxazolidines (HMP and LMP) from a nonaqueous suspension
      (silicone fluid) were compared. Stability-indicating HPLC assays were developed
      for evaluation of the prototype formulations, in which a normal-phase HPLC method
      was necessary for analysis of PO, while a reverse-phase HPLC method was required
      for analysis of the primary degradation product, phenylephrine (PE), following
      its separation from the formulation using a short silica gel column. PO was
      formulated as an ophthalmic suspension in silicone fluid (20 cs) because of its
      property of undergoing rapid hydrolysis in aqueous media. An experimental test
      system for measuring the dissolution characteristics of a water-immiscible
      multiparticulate suspension was designed to obtain the dissolution profiles of
      suspensions of HMP and LMP. The dissolution rates, which were nearly identical
      for LMP and HMP, were obtained assuming a quasi-infinite reservoir. A reverse
      phase HPLC assay with fluorescence detection was used for measuring the
      concentrations of PE in aqueous humor and corneal samples. Statistical analysis
      of the bioavailability data showed that suspensions containing HMP and LMP were
      equal in extent of absorption following a single topical application to the
      rabbit eye. The results correlated well with the in vitro dissolution rates of
      the suspensions of HMP and LMP.

PMID- 8290475
TI  - Utilization of a human intestinal epithelial cell culture system (Caco-2) for
      evaluating cytoprotective agents.
AB  - Human intestinal epithelial cells (Caco-2) were cultured as confluent monolayers
      on polycarbonate membranes in Transwells for investigating their applicability in
      evaluating the cytoprotective activity of sucralfate. The control experiments
      established a reproducible chemical method (using 0.5 mM indomethacin in Hanks'
      balanced salt solution) for inducing damage to the Caco-2 cell monolayers. Damage
      was determined by measuring changes in transepithelial electrical resistance
      (TEER). Twenty-day-old Caco-2 cell monolayers were significantly and reproducibly
      damaged (compared to buffer alone) (P < 0.001) by application of 0.5 mM
      indomethacin to the apical side for 1 hr. While sucralfate, at a 0.5, 2, or 5
      mg/mL concentration in the buffer, was shown not to reverse (treat) the damage
      caused by indomethacin in this cellular model, it was able to protect (prevent)
      the cells from indomethacin-induced damage (P < 0.001). We observed that
      indomethacin-induced damage to the Caco-2 cell monolayers greatly affected the
      paracellular pathway since the percentage transport of [3H]methoxyinulin was
      significantly elevated. In contrast, protection of the Caco-2 cells with 5 mg/mL
      sucralfate in the presence of the damaging agent resulted in transport of the
      paracellular marker similar to that in the control (HBSS-treated) cell
      monolayers. This direct cytoprotective effect was thus independent of vascular
      factors at neutral pH and was observed to be dose dependent (0.5 to 5 mg/mL) when
      sucralfate was applied to the cells in the presence of the damaging
      agent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290477
TI  - Synthesis and enhancing effect of dodecyl 2-(N,N-dimethylamino)propionate on the
      transepidermal delivery of indomethacin, clonidine, and hydrocortisone.
AB  - The biodegradable transdermal penetration enhancer, dodecyl 2-(N,N
      dimethylamino)propionate (II; DDAIP), was prepared by reacting dodecyl 2
      bromopropionate (I), obtained by reaction of n-dodecanol with 2-bromopropionyl
      halogenide, with dimethylamine. The penetration enhancing effects of DDAIP on the
      transport of indomethacin, clonidine, and hydrocortisone across shed snake skin
      (Elaphe obsoleta) were evaluated. Azone and lauryl alcohol, a possible
      decomposition product of DDAIP, were used as standard enhancers for comparison.
      In terms of flux, DDAIP showed 4.7 and 7.5 times the promoting effect for
      indomethacin compared to azone and lauryl alcohol, respectively. With clonidine
      this effect was 1.7 and 3.1 times, whereas with hydrocortisone it was 2.4 and 2.8
      times higher, respectively. In vitro biodegradability of DDAIP was demonstrated
      in the presence of porcine esterase. The results indicate that DDAIP increases
      markedly the transepidermal delivery of several types of drug substances.

PMID- 8290478
TI  - Chemical and alpha-chymotrypsin-mediated proteolytic degradation of insulin in
      bile salt-unsaturated fatty acid mixed micellar systems.
AB  - The proteolytic degradation of porcine zinc insulin by alpha-chymotrypsin was
      previously found to depend markedly on the state of insulin aggregation (Pharm.
      Res. 9:864-869, 1992). In this study, the effect of bile salt-unsaturated fatty
      acid mixed micelles on alpha-chymotryptic degradation of insulin was further
      characterized. The incorporation of linoleic acid has greatly accelerated insulin
      degradation with the apparent first order rate constant being linearly related to
      the concentration of linoleic acid. At a 10 mM linoleic acid concentration
      solubilized in 10 mM sodium glycocholate, the proteolytic degradation rate
      constant increased by 16 times, which could not be explained solely by the
      mechanism of insulin oligomer dissociation. Further, this effect is significantly
      reduced when the free carboxylic group of linoleic acid is methylated. The
      catalytic role of mixed micelles on chemical degradation of insulin was found to
      depend on the concentration of linoleic acid incorporated. When solubilized in
      the form of mixed micelles, linoleic acid chemically catalyzes peptide bond
      cleavage in a concentration-dependent manner.

PMID- 8290479
TI  - A critical comparison of some Raman spectroscopic techniques for studies of human
      stratum corneum.
AB  - This study evaluates a variety of techniques and sampling conditions for Raman
      spectroscopic investigations of human stratum corneum. Using a Fourier-transform
      Raman system and samples of stratum corneum in vitro, we demonstrated minimal
      inter- and intracadaver variations in molecular vibrations. We have also shown
      Raman spectroscopy to be relatively insensitive to the hydration state of human
      stratum corneum, indicating that the technique should be valuable for monitoring
      the transdermal delivery of drugs from aqueous solutions. The stability of human
      stratum corneum to near-infrared laser excitation was verified by spectral
      collection for approximately 1 hr. We have also compared FT-Raman spectra from
      human stratum corneum in vitro and in vivo. Of the different types of Raman
      instruments used in this study (visible-light excitation microprobe, visible
      light excitation macroscopic sampling, and Fourier-transform Raman), the FT-Raman
      system provided good-quality spectra with high sample throughput, but systems
      using visible-light excitation should provide unique information for use in
      specialist applications.

PMID- 8290480
TI  - Stereoselective dissolution of propranolol hydrochloride from hydroxypropyl
      methylcellulose matrices.
AB  - Since many chiral pharmaceutical excipients, such as cellulose polymers and
      cyclodextrins, are used as stationary phases for the separation of enantiomers by
      high performance liquid chromatography (HPLC), it is hypothesized that one
      enantiomer of a chiral drug will be released faster than the other from a
      pharmaceutical formulation containing a racemic drug and a chiral excipient. The
      mechanism of such an event may arise from preferential intermolecular interaction
      between the chiral excipient and one of the enantiomers. To test this hypothesis,
      the release of the enantiomers of propranolol hydrochloride into water from
      formulations containing the chiral excipients, hydroxypropyl methylcellulose
      (HPMC) or beta-cyclodextrin, was investigated by stereospecific HPLC analysis of
      the dissolved concentrations of each of the enantiomers from the formulations.
      The release of the enantiomers of propranolol hydrochloride from the formulations
      containing HPMC, although variable, was found to be stereoselective. However, the
      release of propranolol hydrochloride enantiomers from the beta-cyclodextrin
      complex was found to be non-stereoselective.

PMID- 8290481
TI  - Diffusion of ionizable solutes across planar lipid bilayer membranes: boundary
      layer pH gradients and the effect of buffers.
AB  - The diffusion of weak acids or bases across planar lipid bilayer membranes
      results in aqueous boundary layer pH gradients. If not properly taken into
      account, such pH gradients will lead to errors in estimated membrane permeability
      coefficients, Pm. The role of the permeant concentration, the buffer capacity,
      and the physicochemical properties of both permeant and buffer on the magnitude
      and impact of such pH gradients have been explored. A theoretical model has been
      developed to describe the diffusion of both permeant and buffer species.
      Significant pH gradients develop depending on solution pH and the pKa's,
      concentrations, and Pm values of both permeant and buffer. The relative error in
      experimentally determined Pm values was calculated as the ratio, r, between
      apparent Pm values (obtained from flux measurements using an equation which
      neglected boundary layer pH gradients) and its true value. Simulated r values
      ranged from 1 (0% error) to < 0.01 (> 100% error) for weak acids, decreasing with
      decreasing buffer capacity and increasing solute flux. The buffer capacity
      required for an r > 0.95 was calculated versus pH for permeants varying in pKa
      and Pm. Membrane-permeable buffers significantly reduce boundary layer pH
      gradients through a feedback effect due to buffer cotransport. Apparent Pm values
      of p-hydroxymethyl benzoic acid across lecithin bilayer membranes at 25 degrees C
      were obtained as a function of permeant concentration in various buffers
      [glycolic, 2-(N-morpholino)ethane-sulfonic, and formic acids]. Predictions agreed
      closely with experimental fluxes.

PMID- 8290482
TI  - Transport and hydrolysis of enkephalins in cultured alveolar epithelial
      monolayers.
AB  - An in vitro cultured monolayer system of alveolar epithelial cells was used as a
      model to investigate transport and hydrolysis of two enkephalin peptides, Met
      enkephalin (TGGPM) and [D-Ala2]Met-enkephalinamide (TAGPM), in pulmonary
      epithelium. Isolated alveolar type II cells formed continuous monolayers when
      grown on microporous tissue culture-treated polycarbonate filters in serum-free,
      hormonally defined medium. Transport and hydrolysis studies of enkephalins in the
      monolayer system obtained after 6 days in culture, using fluorescence reversed
      phase HPLC, indicate a reduced but significant degradation of enkephalins in the
      alveolar epithelium compared to most other epithelia previously reported.
      Aminopeptidases and dipeptidyl carboxypeptidase represent two major hydrolytic
      enzymes for TGGPM, as indicated by the formation of the degradative products Tyr
      and Tyr-Gly-Gly, while dipeptidyl peptidase, which is responsible for the
      formation of Tyr-Gly, contributes much less. The enkephalinase inhibitor
      thiorphan failed to prevent the hydrolysis of TGGPM whereas the enkephalin analog
      TAGPM was relatively resistant to enzymatic cleavage. The rate of enkephalin
      transport across the alveolar epithelium was directly proportional to drug
      concentration and occurred irrespective of transport direction, suggesting
      passive diffusion as the major mechanism for transepithelial transport. Agents
      that affect paracellular transport pathways, e.g., EGTA and the calcium ionophore
      A-23187, greatly promoted the transport rate. The ionophore at high doses, in
      addition to promoting tight junction permeability, also caused cellular damage
      associated with a sustained rise in intracellular calcium levels, as indicated by
      nuclear propidium iodide fluorescence. The cultured monolayer of alveolar
      epithelium may be used to study pulmonary drug absorption, degradation, and
      toxicity.

PMID- 8290483
TI  - Dipeptide transport across rat alveolar epithelial cell monolayers.
AB  - The transepithelial transport and metabolism of two model peptides, glycyl-D
      phenylalanine (Gly-D-Phe) and glycyl-L-phenylalanine (Gly-L-Phe), across primary
      cultured monolayers of rat alveolar epithelial cells were studied. These tight
      monolayers (> 2000 omega-cm2) exhibited type I pneumocyte morphological and
      phenotypic characteristics. A reverse-phase HPLC was used to monitor the
      appearance of parent dipeptides and their metabolites (D- or L-Phe) in the
      receiver fluid. The apparent permeability coefficient (Papp) for Gly-D-Phe was
      about 1.6 x 10(-7) cm/sec at both 1 and 10 mM and in both the apical-to
      basolateral (AB) and the basolateral-to-apical (BA) directions. In contrast, the
      Papp of Gly-L-Phe at 1 mM was about two times higher than that at 10 mM in the AB
      direction. The Papp of Gly-L-Phe in the BA direction at either concentration was
      about the same (about 1.4 x 10(-7) cm/sec). Whereas no metabolite was detected
      during Gly-D-Phe transport, the proportions of a metabolite, L-Phe, observed at 4
      hr in the basolateral receiver fluid for 1 and 10 mM apical donor Gly-L-Phe
      accounted for 83 and 77% of the estimated total Gly-L-Phe (i.e., L-Phe+Gly-L
      Phe), respectively. The corresponding values in the BA direction were 40 and 19%
      of the estimated total Gly-L-Phe in the apical receiver reservoir. Metabolism of
      Gly-L-Phe was significantly reduced in the presence of 3 microM actinonin (an
      inhibitor relatively specific for aminopeptides M) in the apical but not the
      basolateral fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290484
TI  - Absorption and disposition of a new antiarrhythmic agent bidisomide in man.
AB  - Absorption and disposition of bidisomide were studied in 12 healthy male subjects
      after a 20-min iv (1 mg/kg; N = 6) infusion and oral (2 mg/kg; N = 6)
      administration of the 14C-labeled drug. The oral absorption profile of unlabeled
      bidisomide was also studied after administration of a solution by a nasoenteric
      tube to different sites of the gastrointestinal tract (stomach, duodenum,
      jejunum, and ileum). The systemic availability was 61%. Absorption was slow
      initially and then rapid, achieving peak plasma concentrations between 2 and 4
      hr. Less than complete systemic availability was attributed to incomplete
      absorption rather than first-pass metabolism. When the drug solution was
      delivered directly to the stomach, two distinct peak plasma levels were found.
      This was attributed to the more rapid absorption of bidisomide in the duodenum
      and ileum (and/or possibly colon). Following an iv dose, plasma levels of the
      drug declined with mean half-lives of 0.11, 2.0, and 12 hr for alpha, beta, and
      gamma phases, respectively, and a plasma clearance of 380 mL/min. The percentages
      of the dose recovered as bidisomide in urine and feces were 19 +/- 1 and 29 +/- 4
      for the iv dose and 9.1 +/- 0.9 and 48 +/- 5 for the oral dose. Bidisomide did
      not exhibit substantial enantioselective pharmacokinetics in plasma regardless of
      the route of administration. The mean urinary excretion of the (-) enantiomer
      was, however, slightly higher than that of the (+) enantiomer, with (-)/(+)
      enantiomeric ratios of 1.2 and 1.3 after iv and oral administration,
      respectively. The enantiomeric ratio of bidisomide recovered in the feces was
      approximately 1.

PMID- 8290485
TI  - Evaluation of sustained/controlled-release dosage forms of 3-hydroxy-3
      methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors in dogs and humans.
AB  - Seven sustained/controlled-release dosage forms were designed for
      gastrointestinal delivery of lovastatin or simvastatin, two potent HMG-CoA
      reductase inhibitors for the treatment of hypercholesterolemia. The in vivo
      performance of these formulations was evaluated in dogs and healthy volunteers in
      terms of the cholesterol lowering efficacy and/or systemic concentrations of HMG
      CoA reductase inhibitors. Results from the present and previous studies suggest
      that, through the controlled release of HMG-CoA reductase inhibitors, sustained
      lower plasma concentrations of HMG-CoA reductase inhibitors may result in an
      equal or better therapeutic efficacy.

PMID- 8290486
TI  - Application of dual radiotelemetric technique in studying drug-drug interaction
      between diclofenac sodium and ranitidine HCl in volunteers.
AB  - Drug-drug interaction between a commercial diclofenac sodium enteric-coated
      tablet (Voltaren; V) and a ranitidine HCl tablet (Zantac; Z) was evaluated using
      a dual radiotelemetric technique according to a randomized three-way Latin-Square
      crossover design balanced for carryover effects. V and Z were given either alone
      or in combination (Treatment V, Z, V/Z), with a 14-day washout period between
      treatments. Eighteen fasted subjects swallowed a tethered. Heidelberg pH capsule
      to provide continuous gastric pH. Then the assigned treatment drug and another
      Heidelberg pH capsule were given simultaneously. The free pH capsule provided
      information regarding gastric residence time (GRT). Serial blood samples were
      obtained for up to 12 hr after dosing and drug levels were determined by
      validated HPLC methods. Treatment effects on AUC, Cmax, Tmax, Tlag, Tmax-Tlag,
      and T1/2 were not significant except Cmax, which differed slightly for both V and
      Z when given in combination as compared to alone. Gastric residence times were
      46, 33, and 51 min for Treatments V, Z, and V/Z, respectively. Gastric exposure
      of the enteric-coated tablet of diclofenac was estimated by pH values obtained
      from the tethered capsule. Median pH values at 3 and 15 min prior to gastric
      emptying were 3.8 and 4.9 for the combination treatment versus 2.1 and 2.7 for
      diclofenac alone. The results of this study indicated that there was minimal drug
      drug interaction between diclofenac and ranitidine. The gastric pH range
      resulting from this study did not influence the oral absorption of enteric-coated
      diclofenac.

PMID- 8290487
TI  - Prediction of drug release from hydroxypropyl methylcellulose (HPMC) matrices:
      effect of polymer concentration.

PMID- 8290488
TI  - Oligonucleotides get a face-lift.

PMID- 8290489
TI  - Current topic: placental surgery: a new frontier.

PMID- 8290490
TI  - Histochemical localization of glucose residues in the human term placenta.
AB  - Glucose residues were revealed by light microscopic and fine structural analysis
      using hexokinase-gold conjugate. In human term placenta specific staining was
      detected over the stroma of placental villi. Colloidal gold particles were found
      over the collagen fibrils and reticular lamina of basal membrane.
      Syncytiotrophoblast cells, fibroblasts, endothelial cells of fetal capillaries
      were void of labelling. Nucleated blood cells and thrombocytes inside the lumen
      of fetal capillaries possessed intense labelling. In the present investigation
      the process of extracellular glycosylation of collagen was histochemically
      demonstrated.

PMID- 8290491
TI  - Glycogen distribution in the capillaries of the placental villus in normal, overt
      and gestational diabetic pregnancy.
AB  - Glycogen distribution has been examined in placental capillaries in normal (N;
      11), overtly diabetic (OD; 8) and gestational diabetic (GD; 7) pregnancies using
      light and electron histochemistry. Light microscopy revealed a wide variation in
      glycogen deposition in all three groups, but the method was too insensitive to
      visualize deposits in the villous capillaries. An ultrahistochemical technique,
      however, rendered glycogen detectable. Endothelial cells (EC) and pericytes
      (PERI) in 100 capillaries per specimen were scored as to whether their glycogen
      was dispersed (D) or aggregated (A). Again, a large range in the amounts of both
      types of glycogen was seen. When EC and PERI comprising a capillary cross-section
      were considered together as 'functional units', a higher (P < 0.11) relative
      number of cells containing A was found in OD (51 +/- 8 per cent) than in N (41 +/
      17 per cent) or GD (43 +/- 18 per cent). In OD more EC and PERI, considered
      separately, tended to contain A than those in N and GD, but large variations in
      the data precluded statistical significance. The proportion of PERI containing
      aggregated glycogen was higher (P < 0.0002) than that of EC in all groups. We
      suggest that, on average, placental EC and PERI contain higher glycogen levels in
      OD than in N or GD. Moreover, these cells might contribute to the high glycogen
      levels in placentae from diabetic pregnancies.

PMID- 8290492
TI  - Studies on placental inhibition of platelet aggregation: a comparison of human
      syncytiotrophoblast brush border and basal plasma membranes.
AB  - We compared the platelet aggregation inhibiting activity of human placental
      syncytiotrophoblast brush border membrane vesicles (BBMV) and basal plasma
      membrane vesicles (BpMV), and obtained the following results. Strong platelet
      aggregation inhibiting activity is found in placental BBMV. BBMV inhibited
      platelet aggregation induced by ADP (adenosine diphosphate) and arachidonic acid
      in a way which depended on the protein concentration of BBMV added. In contrast,
      BpMV showed no detectable platelet aggregation inhibiting activity. Quite high
      ADP degrading activity (ADPase activity) was present in the placental BBMV. ADP
      was quickly degraded by BBMV. In contrast, BpMV did not degrade ADP so quickly.
      Platelet TXB2 production was almost completely abolished at the protein
      concentration of 40 micrograms/ml of BBMV. In contrast, BpMV did not
      significantly inhibit platelet TXA2 (TXB2) production. These results show that
      syncytiotrophoblast brush border and basal plasma membranes of the human placenta
      have markedly different properties with respect to platelet aggregation
      inhibiting activity.

PMID- 8290493
TI  - Trophoblast cell differentiation and organization: role of fetal and ovarian
      signals.
AB  - The rat chorioallantoic placenta is organized into two distinct zones (junctional
      and labyrinth) and expresses six members of the placental prolactin (PRL) family:
      placental lactogen-I (PL-I), PL-I variant (PL-Iv), PL-II, PRL-like protein-A (PLP
      A), PLP-B, and PLP-C. These placental hormones are expressed in distinct cell-
      and temporal-specific patterns and can be used to monitor the state of
      differentiation of rat trophoblast cells. This study was initiated to examine the
      role of the fetus and maternal ovaries in the regulation of trophoblast cell
      differentiation and organization. Expression of the placental PRL family was
      monitored by Northern and Western blotting and immunocytochemical analysis. The
      roles of the fetus and maternal ovaries were examined by chemically induced fetal
      death (DFX, induced by intraamniotic injection of digoxin) and surgical removal
      of the ovaries (OVX), respectively. The endocrine differentiation of the placenta
      was assessed on day 19 of gestation (sperm positive = day 0, parturition = day
      21). Day 10 of gestation was the earliest day that DFX could be reliably
      performed. Day 10 is a time point during pregnancy preceding the onset of
      expression of all members of the placental PRL family except PL-I. DFX on day 10
      of gestation did not affect the endocrine differentiation of the trophoblast
      cells but did alter the organization of the chorioallantoic placenta. PL-II, PL
      Iv, and the PLPs were all expressed in their appropriate molecular forms and cell
      types in placentas developing in the absence of fetal influence. The maternal
      ovaries, in the absence of the fetus, had two distinct actions on the placenta:
      ovarian signals were essential during a period at midgestation for the
      maintenance of the placenta and exposure of the developing placenta to ovarian
      signals during the second half of gestation, in the absence of the fetus,
      arrested labyrinth zone development. The active ovarian signals were progesterone
      and estrogen. We conclude that trophoblast cell differentiation occurs
      independent of the fetus and maternal ovaries. However, signals from both the
      fetus and maternal ovaries are required for normal organization of the
      chorioallantoic placenta.

PMID- 8290495
TI  - Blood viscosity and uterine artery flow velocity waveforms in pregnancy: a
      longitudinal study.
AB  - In the course of pregnancy, whole blood viscosity (WBV) decreases, plasma
      viscosity (PV) increases and uteroplacental resistance to blood flow falls.
      According to the Hagen-Poiseuille law, viscosity influences resistance to blood
      flow. To investigate the contribution of these haemorheological changes to the
      decrease in resistance to blood flow in the uteroplacental circulation, a serial
      study was performed. Using blood viscosimetry and pulsed Doppler ultrasound
      recordings of the uterine arteries, 21 women with normal pregnancies were studied
      every 8 weeks from 12 weeks onwards. Statistical analysis revealed no significant
      relationship between WBV, PV and pulsatility index of the uterine arteries. It is
      concluded that the changes in blood viscosities are of minor influence on
      resistance to blood flow in the uteroplacental circulation throughout normal
      pregnancy. The vascular changes e.g. the considerable increase of the diameter of
      the spiral arteries have a much greater impact on resistance to blood flow.

PMID- 8290494
TI  - Nucleoside transport by perfused human placenta.
AB  - Nucleoside transport and metabolism by human placenta was studied using the dual
      perfusion technique. With [3H] thymidine added to the maternal perfusate and
      neither perfusate recirculated (steady-state studies) around 40 per cent of the
      thymidine in the maternal outflow and 50 per cent of the transferred thymidine
      was degraded. In similar studies with adenosine, over 95 per cent of the
      nucleoside was degraded. Even with the bolus technique which sharply limits the
      duration of contact with the placenta, degradation of adenosine was over 95 per
      cent. Uptake as calculated by the dual-tracer method ([3H] adenosine/[14C] L
      glucose) was equally rapid from the maternal and fetal perfusates, was saturable
      and inhibited by nitrosobenzylthioinosine, consistent with the facilitated
      diffusion system for nucleosides. Thymidine was taken up at one-third the rate of
      adenosine. Thymidine in large excess (500 microM) reduced adenosine uptake
      suggesting a common transporter. Zidovudine, a thymidine analogue used for the
      treatment of AIDS in which the ribose is modified at the 2' 3' position, did not
      compete with adenosine for uptake consistent with previous reports that
      zidovudine is transferred across the placenta by simple diffusion.

PMID- 8290496
TI  - Contractile responses of the human umbilical artery from pregnancies complicated
      by intrauterine growth retardation.
AB  - The contractile properties of the umbilical artery to oxygen, U46619 (a stable
      thromboxane A2 mimetic) and 5-hydroxytryptamine (5-HT) were studied in normal
      term (> or = 37 weeks) and preterm (< 34 weeks) pregnancies, and in a group of
      pregnancies complicated by intrauterine growth retardation (IUGR). Isometric
      contractile responses in the preterm group to oxygen were reduced when compared
      with the term group, though no differences were found between these groups in the
      responses to either U46619 or 5-HT. In the IUGR group the responses to oxygen did
      not differ from gestationally matched normal pregnancies, though among those
      cases delivered preterm, the finding of absent end-diastolic flow velocity in the
      umbilical artery prior to delivery was associated with markedly diminished
      responses to oxygen. These data indicate the development of oxygen-induced
      contractions in the umbilical artery as pregnancy advances, which may fail to
      function in the severely growth-retarded fetus.

PMID- 8290497
TI  - Pregnancy specific beta 1 glycoprotein (SP-1) in maternal serum and amniotic
      fluid; pre-eclampsia, small for gestational age fetus and fetal distress.
AB  - Pregnancy specific beta 1 glycoprotein (SP-1) levels have been suggested to
      correlate with certain obstetrical complications. We compared maternal serum SP-1
      levels in normal pregnancies (N = 82), and pregnancies complicated by pre
      eclampsia (N = 37), small for gestational age fetuses (N = 8) and fetal distress
      (N = 13). We also compared levels of this protein in mid-trimester amniotic fluid
      samples obtained from normal (N = 47) and small for gestational age fetuses (N =
      25). Despite trends towards low maternal serum and amniotic fluid SP-1 values in
      complicated pregnancies, there were no statistically significant differences in
      their levels as compared with normal gestational age matched controls (P > 0.05).
      These data do not support the use of SP-1 values in clinical practice.

PMID- 8290498
TI  - Branching patterns of human placental villous trees: perspectives of topological
      analysis.
AB  - Topological analysis was applied to investigate the branching pattern of three
      specimens obtained from early human placenta (6, 9, and 16 weeks p.m.)
      reconstructed on the basis of semi-thin sections. Centripetal Horton-Strahler and
      centrifugal branching order nomenclature was used for topological description of
      the analysed tree-like structures. Bifurcation ratio and vertex ratio were
      determined for all three cases and were found to be relatively constant. It was
      shown that branching pattern is closely related to the model of random segment
      branching that implicates a high level of asymmetry and a small level of space
      limitation for branching. The significance of this approach for the analysis of
      development of the villous tree, for the analysis of mesenchymal villous
      heterogeneity, and for the estimation of physiological parameters for
      fetoplacental exchange is discussed. We suggest that topological analysis can
      lead to a new quantitative classification of branching patterns of the human
      placental villous trees in normal and pathologic pregnancies.

PMID- 8290499
TI  - [Atherogenic potential of blood serum in patients with type I diabetes mellitus].
AB  - The task of this research was to study exogenous insulin effect on blood serum
      atherogenic potential in patients with type I diabetes mellitus. Under study were
      relationship between blood serum atherogenic potential in diabetics and daily
      insulin dose and duration of therapy, as well as exogenous insulin effect on the
      major atherosclerotic manifestations in tissue cultures, such as intracellular
      cholesterol content in cultured cells and labeled thymidine incorporation in
      cellular nuclei DNA. Blood serum atherogenicity did not correlate with insulin
      dose and duration of insulin therapy both in adult patients and children. Insulin
      prescription to newly detected patients with type I condition did not influence
      blood serum atherogenic potential. Exogenic insulin did not influence the major
      atherosclerotic manifestations at the cellular level, namely, on intracellular
      cholesterol content in cultured cells and these cells proliferative activity; it
      had no influence on blood serum atherogenic potential of the patients with type I
      condition.

PMID- 8290500
TI  - [Fetoplacental hormone complex measurements to predict fetal and neonatal
      viability in insulin-dependent diabetes mellitus].
AB  - A dynamic follow-up of 79 pregnant patients with insulin-dependent diabetes
      mellitus was carried out. Specific fetoplacental hormonal profiles were detected
      and analyzed in complex with glycemic levels, this permitting the authors obtain
      new prognostic criteria of fetal and newborn viability. The results helped
      optimize the policy of following up such patients and the developed prediction
      regulations allowed preventive measures aimed at improvement of the future baby
      health status to be carried out before clinical manifestation of fetal
      intrauterine suffering.

PMID- 8290501
TI  - [Urinary catecholamine excretion and blood serotonin content in juvenile
      hypothalamic syndrome].
AB  - Daily urinary adrenalin, noradrenaline, dopamine excretion and blood levels of
      serotonin were measured over the course of the cycle in 8 healthy girls and in 52
      patients with the juvenile hypothalamic syndrome in the acute and chronic stages.
      These parameters were found virtually the same in healthy girls and in those
      suffering from the hypothalamic syndrome in the course of the cycle or in
      patients during the acute and chronic stages of the condition. Urinary
      catecholamine excretion and blood serotonin levels were increased by 1.5-2 times
      in the acute stage of the syndrome and somewhat reduced in the chronic stage;
      this appears to be due to reduced activity of the sympathoadrenal system in the
      course of disease progress.

PMID- 8290502
TI  - [Adrenal gland surgery in endogenous hypercorticism].

PMID- 8290503
TI  - [Association of multinodular euthyroid colloid goiter with various genetic
      markers].
AB  - Distribution of blood groups ABO, Rh, P1, and MN was studied in 85 patients with
      multinodular euthyroid colloid goitre. An association has been revealed between
      the presence of this disease and MN blood group, as well as the absence of P1
      antigen. These results permit us considering MN blood group and P1 antigen
      absence as factors of risk for multinodular euthyroid colloid goitre.

PMID- 8290504
TI  - [Pathogenesis of thyroalgia].
AB  - The authors analyze thyroalgias occurring in various thyroid diseases and
      diseases of the adjacent organs and tissues. They come to a conclusion that as
      far as thyroid diseases are concerned, true thyroalgias are the most incident in
      various thyroiditis forms, thyroid tumors, postoperative cicatrices, and are
      explained by the pathologic process impact on glandular capsule (stretching,
      intergrowth, pressure, etc.). Of diseases not directly related to thyroid but
      causing thyroalgias (pseudothyroalgias) laryngitis, pharyngitis, and osseous
      conditions are the most incident, which indirectly influence pain development.
      Pseudothyroalgias should be differentiated from such osseous changes in the neck
      as deforming spondylosis, spondylarthrosis, extra cervical ribs (a developmental
      abnormality), and structural specificities of temporal bone styloid processes.

PMID- 8290505
TI  - [Fine needle puncture biopsy and methods to image the thyroid gland in the
      diagnosis of nodular goiter].
AB  - A retrospective analysis of the findings of fine needle puncture biopsy of the
      thyroid in 256 patients operated on for nodular goiter is presented. Cytologic
      findings coincided with the histologic in 84.8% of cases. The coincidences were
      the most frequent in (multiple) nodular colloid goiter and thyroid cysts (95.7 =
      100%) and the least so in solitary adenoma (65.4%) predominantly of a follicular
      structure. In thyroid cancer the data correlated in 75% of cases. The presence of
      cystous changes in adenoma made the investigation less informative. Findings of
      ultrasonic examination of the thyroid coincided with operative findings in 87.5%
      of patients with (multiple) nodular goiter and in 86.1% of those with adenomas.
      Ultrasonography as a method for thyroid imaging is preferable to scintigraphy
      (scanning) and is an optimal supplement to puncture biopsy of the thyroid.

PMID- 8290507
TI  - [Use of glycemic indices in diet therapy of diabetes mellitus (lecture)].

PMID- 8290506
TI  - [A case of thyroid cancer involving the root of the tongue].

PMID- 8290508
TI  - [Drug correction of hypotonic dyskinesia of the gallbladder in patients with
      diabetes mellitus].

PMID- 8290509
TI  - [Glycemic indexes of products and dishes in planning nutrition of patients with
      insulin-dependent diabetes mellitus].

PMID- 8290510
TI  - [Diabetes mellitus incidence and its prevalence in Moscow].
AB  - Epidemiologic survey of two diabetes mellitus types in Moscow has shown that the
      incidence of type I diabetes markedly increases from birth (0.012-0.013%) to the
      age of 10-14 (0.04-0.045%), after which somewhat reduces (0.02-0.03%) and thus
      persists up to 40. Type I diabetes prevalence increases from 0.002-0.004% at the
      age of 0 to 4 years to 0.14-0.092% by the age of 35-39 in men and women,
      respectively. Type II diabetes is diagnosed after the age of 20. At the age of 20
      to 24 this diabetes incidence is lower than that of type I condition; at the age
      of 25-34 the incidence of both is approximately the same, and after 35 the
      incidence of type II is much higher than that of type I diabetes. Type II
      diabetes prevalence by the age of 40 is 0.074 and 0.122% in men and women,
      respectively. Prevalence of diabetes cases treated with diets and oral sugar
      reducing drugs at the age 75 and older is 4.3% in men and 5.5% in women, of
      insulin-treated cases 1.2 and 0.5%, respectively. The true prevalence of type II
      diabetes is however higher and that of type I condition lower than the resultant
      values; this is explained by a frequent prescription of insulin to elderly
      patients with type II diabetes because of complications or concomitant diseases.

PMID- 8290511
TI  - [Effect of chorionic gonadotropin on formation of secondary immune response].
AB  - Experiments were carried out in vivo and in vitro. Secondary immune response to
      sheep red cells was assessed on day 5 after repeated immunization by IgM and IgG
      antibody-producing cells. Chorionic gonadotropin was injected after
      reimmunization to intact and ovariectomized animals in doses compatible to those
      in normal pregnancy. In vitro chorionic gonadotropin was added for one h into
      sensitized splenocyte cultures and then its effects were assessed in syngeneic
      transfer system by the same parameters. Experiments have demonstrated that in
      dose 40 MU chorionic gonadotropin cannot influence secondary immune response
      formation. All hormonal effects are related to 200 MU dose extrapolated from the
      maximal level of this hormone during pregnancy. In this dose gonadotropin reduced
      splenocyte counts and inhibited the formation of IgG-antibody-producing cells.
      Ovarian sex steroids do not mediate chorionic gonadotropin immunomodulating
      effects. An hour's contact of sensitized splenocytes with the hormone in a high
      dose resulted in a statistically significant inhibition of the formation of IgM
      antibody-producing cells. Hence, if chorionic gonadotropin interacted with
      immunocompetent cells before their repeated contact with the antigen, IgM
      antibody-producing cells suffer, and if this exposure occurs after this contact,
      IgG-antibody-producing cells decrease in number. The role of chorionic
      gonadotropin in development of normal pregnancy and that complicated by
      immunopathologic processes is discussed.

PMID- 8290512
TI  - [Kinetic parameters of GABA receptor binding by rat adenohypophyseal membranes
      under conditions of modelling various corticosteroid and ACTH levels in the
      body].
AB  - Kinetic parameters of 14C-GABA specific binding by rat adenohypophyseal plasma
      membranes were studied in experiments on modelling various corticosteroid and
      ACTH levels in animal body. A single hydrocortisone injection did not change K
      alpha for high- and low-affinity GABA receptors, the number of the former (Bmax)
      increasing in this case. Repeated hydrocortisone injections were associated with
      K alpha reduction for high-affinity GABA receptors and a noticeable increase of K
      alpha for low-affinity receptors, with their number reducing. ACTH injection did
      not change the kinetic parameters of GABA binding with receptors. The number of
      high-affinity GABA receptors and their affinity reduced after removal of adrenals
      whereas the number of low-affinity receptors in this case was increasing. A
      single hydrocortisone injection to adrenalectomized rats had a normalizing effect
      on adenohypophyseal GABA receptors. Analysis of the results and changes in blood
      hormonal levels indicated that affinity changes in high-affinity receptors and
      changed number of low-affinity adenohypophyseal GABA receptors correlated with
      changes in ACTH and hydrocortisone changes.

PMID- 8290513
TI  - [Interactions between serum antibodies of patients with autoimmune thyropathies
      and isolated cells of diffuse toxic euthyroid nodular goiter].
AB  - Blood sera of 46 patients with diffuse toxic goiter (DTG) and of 48 ones with
      Hashimoto's thyroiditis (HT) were tested for antibodies--complement-mediated
      cytotoxicity carriers (ACMMC). ACMCC targets were isolated DTG cells and cells of
      euthyroid nodular goiter (ENG) perinodular tissue. Antimicrosomal antibodies were
      assayed in the sera by indirect immunofluorescence and antibodies to all
      thyrocyte surface antigens isolated from both tissue samples were determined by
      solid-phase enzyme immunoassay. When DTG cells were targets, DTG patients' sera
      detected ACMCC in 36% of cases and HT patients' sera in 73% of cases (p < 0.001).
      In ENG cells the sera of patients of both groups detected ACMCC equally
      frequently (in more than 70% of cases). Of the 27 DTG patients' sera tested with
      both tissues approximately a half detected ACMCC in only ENG tissue. There was no
      difference in HT patients' sera effects on ACMCC detection in both tissue
      samples. This has brought the authors to a conclusion about DTG cells deficiency
      for ACMCC mediating antigens. Moreover, DTG cells bound much less antibodies from
      sera of patients with autoimmune thyropathies, than ENG cells (p < 0.001), this
      confirming a deficiency of surface antigen on DTG cells. No correlation between
      the presence in the sera of antimicrosomal cells and of ACMCC was detected. A
      conclusion has been made about heterogeneity of antimicrosomal antibody
      population and about the presence of ACMCC in blood sera of patients with
      autoimmune thyropathies, these antibodies not belonging to antimicrosomal ones.
      ACMCC also may be heterogeneous and differ in DTG and HT patients.

PMID- 8290515
TI  - [Hypophyseal-adrenocortical system in experimental hereditary hypertension].

PMID- 8290514
TI  - Sympatho-adrenal system activation by administration of corticoliberin in the dog
      caudate nucleus.
AB  - Corticotrophin releasing factor injection into the head of the caudate nucleus of
      dogs was followed by a more than threefold increase of blood plasma adrenaline
      and noradrenaline levels as soon as in 30 min and by their reduction by the 60th
      min after the injection though not to the initial values. These changes are
      compatible to stressor reaction and are associated with an increased orientation
      research reaction in animals. Injections of 6-hydroxydopamine into caudate
      nucleus drastically exhausted dopamine content in this structure. Subsequent
      injections of corticotrophin releasing factor into caudate nucleus virtually did
      not change blood plasma catecholamine content, this indicating the participation
      of the strionigral complex dopaminergic structures in realization of
      corticotrophin releasing factor effect on the sympathoadrenal system.

PMID- 8290516
TI  - [Use of magnetic resonance tomography in the diagnosis of diseases of the
      hypothalamo-hypophyseal system].

PMID- 8290518
TI  - [Dynamics of the prevalence of non-insulin-dependent diabetes mellitus (10-year
      prospective study)].
AB  - Carbohydrate metabolism was tested in 2468 subjects (male and female) aged 20 to
      69 living in one of Moscow districts by means of standard oral glucose tolerance
      test. Primary screening was carried out in 1979, repeated in 1989. The results
      indicate an evident increase in the incidence of noninsulin-dependent diabetes
      mellitus both among men and women. The disease incidence in women was reliably
      higher than in age-matched men. Prevalence of the condition among women was
      characterized by a lower, in comparison with that among men, parameters of its
      time course.

PMID- 8290517
TI  - [Myocardial function in patients with type I diabetes mellitus].
AB  - Myocardial contractility was examined in patients with type I diabetes mellitus
      without coronary disease by selective tolerance test with transesophageal heart
      stimulation using doppler cardiography. Nineteen diabetics aged 17 to 36 with the
      disease duration from 0 to 20 years were examined. Maximal ejection time before
      and after the test was assessed. The findings indicate impaired myocardial
      contractility in the examinees, though clinical signs of manifest circulation
      insufficiency were undetectable in all the patients. The authors come to a
      conclusion on the significance of diabetes duration and severity in development
      of myocardial injury.

PMID- 8290519
TI  - [Optimization of the times of temporary work incapacity to prevent disability
      from tuberculosis].
AB  - Sickness certificates for prolonged recovery terms (by 2.5 months, on the
      average) were given to 330 tuberculous patients. It is shown that when the
      disability expert commission fixed prolonged terms for convalescence (10 months
      and longer) for tuberculous patients, this led to the disease stabilization in
      90% of the patients who were able to resume their previous work. Only 10% of them
      became invalids.

PMID- 8290520
TI  - [The organization of the dispensary observation of patients with respiratory
      organ sarcoidosis].
AB  - The paper deals with organizational questions regarding monitoring survey of
      respiratory sarcoidosis patients in anti-tuberculous institutions. It is
      suggested to recognize among the VIII group registrants subgroups A, B and D
      including patients with active sarcoidosis, stable regression, marked
      pneumosclerosis with respiratory distress. The authors give details how to
      distribute patients by subgroups, a scope of control examinations, rules of
      withdrawal from the follow-up.

PMID- 8290521
TI  - [Acute tuberculous pneumonias (exudative and caseous)].
AB  - Clinical, x-ray and morphological characteristics are presented for acute
      tuberculous pneumonia in 56 patients. The diagnosis was established intravitally
      in 33, postmortem in 23 of them. The disease started acutely and terminated
      fulminantly in all the patients. A morphological study stated predominance of
      exudative-necrotic reaction without phasic and productive changes, the presence
      of M. tuberculosis in the tissues.

PMID- 8290522
TI  - [The clinico-immunological variants of drug-induced toxic hepatitis in pulmonary
      tuberculosis patients].
AB  - Clinical and immunological variants were assessed in 62 patients with toxic drug
      hepatitis due to tuberculostatic therapy. Three clinicoimmunological variants of
      toxic hepatitis were recognized. They need to be accounted for when deciding on
      immunocorrection.

PMID- 8290523
TI  - [The Zivert-Kartagener syndrome in children].
AB  - A comprehensive clinicomorphological examination of 24 children with Zivert
      Kartagener syndrome ascertained the complete triad (bronchiectasis,
      maldevelopment of the sinuses and transposition of the viscera) in all of them.
      Initial signs of the respiratory affection are shown to arise early. The disease
      progression depended primarily on the scope of pulmonary damage. Electron
      microscopic findings at examination of the patients' tracheal mucosa obtained at
      bronchoscopy revealed reduced number of ciliary cells and abnormal inner
      structure of the cilia. The impairment in some patients was focal. The attention
      is drawn to the benefit of early diagnosis and follow-up for such patients who
      should be treated surgically after careful consideration of potential risks.

PMID- 8290524
TI  - [The x-ray functional characteristics of chronic bronchitis].
AB  - A significant correlation has been established at comparison of fluorographic
      findings with respiratory mechanics in bronchitis chronic between the diaphragm
      height, its curvature in the lateral view and FEV for the 1st second. Less
      apparent correlation exists between residual lung capacity and the diaphragm
      height, forced expiration volume and the width of the pulmonary artery right
      branch. Tracheobronchial dyskinesia was diagnosed in 62.2% of bronchitis
      patients. Chronic nonobstructive bronchitis is characterized by a short-term (> 1
      s) prolapse of the tracheal posterior wall and primary bronchi which lasts longer
      (1-3 s) in chronic obstructive bronchitis.

PMID- 8290525
TI  - [Erythema nodosum in sarcoidosis patients].
AB  - Erythema nodosum was registered in 45 from 502 sarcoidosis patients (9%).
      Erythema often arose in initial sarcoidosis, but was also recorded in the disease
      recurrences. Sarcoidosis of the skin and subcutaneous fat occurred in 16 and 4
      patients, respectively, this incidence being half of that for erythema nodosum.
      Sarcoidosis of the above sites is the second in occurrence among extrapulmonary
      lesions following those of peripheral lymph nodes. Positive effects in the
      treatment of erythema nodosum were reached after administration of
      corticosteroids, noncorticosteroid anti-inflammatory drugs, physiotherapy, local
      therapy.

PMID- 8290526
TI  - [A new method of compression arthrodesis in the surgery of hip joint
      tuberculosis].
AB  - An original method of hip joint arthrodesis developed by the authors makes use of
      a rod compression apparatus different from usable designs by a new construction
      of the hip fragment implying a hooked fixator and rods with two carved parts. The
      method was tried in 12 patients with tuberculous coxitis with good results.

PMID- 8290527
TI  - [The microbiological diagnosis of tuberculosis in areas under strict radiation
      control].
AB  - Mycobacterial variability was studied in active tuberculosis patients from
      radioactive contamination area subject to close radiation control. For such areas
      it was noted that the patients discharge altered coccoid mycobacteria stained
      with routine luminescent dyes. Biological investigations of freshly isolated
      strains revealed potentiation of M. tuberculosis virulence in patients with
      respiratory tuberculosis. A large number of patients from the contaminated areas
      against control demonstrated primary resistance to rifampicin and isoniazid.

PMID- 8290528
TI  - [Erythrocyte metabolism during chemotherapy in pulmonary tuberculosis patients].
AB  - Pre- and posttreatment (13 months after polychemotherapy) activity of key
      bioenergetic enzymes (LDG and G-6-FDG) and enzymes of antioxidant defense (GPO
      and GR) was measured in red cells of 88 patients with pulmonary tuberculosis.
      Pretreatment red cell metabolism of such patients was characterized by
      compensatory and pathological changes: LDG and GR activity enhanced, while G-6
      FDG and GPO activity inhibited. Three months after the treatment LDG, GPO and GR
      activities completely or partially returned to normal values. G-6-FDG activity in
      quick treatment responders remained low, in poor response this enzyme activity
      tended to a decrease. Administration of riboxin as the antihypoxant or ascorbic
      acid as the antioxidant prevented progressive inhibition of G-6-FDG activity
      during the chemotherapy and led to a significant improvement of the treatment
      results.

PMID- 8290529
TI  - [The effect of long-wave laser radiation on the NADP-dependent dehydrogenase
      activity of the blood lymphocytes in healthy persons and pulmonary tuberculosis
      patients].
AB  - A study was made to elucidate the in vitro effects of long-wave laser irradiation
      on NAD(P)-dependent lymphocytic dehydrogenases in peripheral blood of healthy
      subjects and patients with fibrous-cavernous tuberculosis of the lungs. In
      addition to suppression of T-cell immunity and reinforcement of humoral factors,
      such patients demonstrated predominance of catabolic processes over anabolic,
      reduction of the substrate flow by Krebs cycle. The above phenomena explain
      different responses to long-wave laser irradiation (632 nm) in healthy subjects
      and tuberculous patients who are noticed to develop more active transfer of the
      lipid catabolism products to glycolysis.

PMID- 8290530
TI  - [The immunological aspects of metatuberculous pneumosclerosis].
AB  - It was found that a relationship exists between x-ray changes in the lungs,
      levels of IgG, IgM, IgA, antibodies counts in tuberculin enzyme immunoassay,
      circulating immune complexes (CIC), heterophilic antibodies and metatuberculous
      pneumosclerosis in patients with a history of active tuberculosis. A direct
      relationship was established between the advance of metatuberculous
      pneumosclerosis and CIC levels. The latter clearly reflect basic immunological
      mechanisms of fibrogenesis.

PMID- 8290531
TI  - [The importance of serological studies in assessing the activity of urinary
      system tuberculosis].

PMID- 8290532
TI  - [The use of preparations of methazid combined with riboflavin and pyridoxine for
      the correction of methazid-induced metabolic disorders of the B-group vitamins in
      rats].
AB  - It was established that 10-day administration of suppository methazide (20 mg per
      100 g b. w.) induces B2 vitamin deficiency indicated by relevant hepatic and
      plasmic values. In vitamin B2 deficiency methazide-induced changes in vitamin B6
      metabolism are less marked in rats provided with riboflavin. Use of suppository
      methazide in combination with riboflavin (100 micrograms per animal which is a
      recommended daily dose) prevents B2 deficiency. It is recommended daily use
      combinations of methazide with riboflavin or piridoxin in essential daily
      consumption doses to treat patients with alimentary vitamin B2 and B6
      deficiencies. This will not only prevent side effects of methazide, but also help
      to overcome deficiency of the above vitamins.

PMID- 8290533
TI  - [The isolation of monoclonal antibodies to strains of Mycobacterium leprae passed
      through laboratory animals].
AB  - Hybridoma synthetizing monoclonal antibodies (mAB) IIIE4 has been obtained in
      hybridization of myeloma P3-X63-Ag8. 653 cells and splenocytes from BALB/c mice
      immunized with M. leprae passaged on rats. The mAB specificity evaluated by
      enzyme immunoassay using ultrasonic disintegrates of M. leprae obtained from
      human, Dasypus novemcinctus, rat lepromas as well as mycobacteria of 7 species
      and E. coli indicated that the mAB reacted only with mycobacteria passaged on the
      rats. They had weak cross reactivity with M. avium.

PMID- 8290534
TI  - [The diagnosis and treatment of respiratory organ sarcoidosis (methodological
      recommendations). The Central Research Institute of Tuberculosis of the Russian
      Academy of Medical Sciences].

PMID- 8290535
TI  - [The determination of mycobacterial antigens found in immune complexes].
AB  - By using affine isolation from hyperimmune rabbit sera on homologous mycobacteria
      humanus (H37Rv) and affine purification on atypical mycobacteria and BCG
      mycobacteria, the authors obtained a preparation of antituberculous antibodies.
      These were used in indirect ELISA to detect antigens (after IC dissociation) in
      tuberculous patients. Out of 70 patients with infiltrative pulmonary
      tuberculosis, 30 patients with other pulmonary diseases and 30 healthy donors the
      antigens were found in 77.1% of tuberculous cases and in 6.7% of healthy
      subjects. The results of the test say in favour of its benefits in practical
      application. The antigens levels and incidence of positive reaction are higher in
      patients with destructive tuberculosis and in the bacterial discharge.

PMID- 8290536
TI  - [Pulmonary tuberculoma as a clinical form of respiratory organ tuberculosis].

PMID- 8290537
TI  - [A method for the rational treatment of pulmonary tuberculosis patients in the
      hospital].

PMID- 8290538
TI  - [Tuberculosis of the eyes].

PMID- 8290539
TI  - [Prof. A. I. Kudriavtseva--the founder of the prophylactic trend in tuberculosis
      care for the pediatric population (on the centenary of her birth)].

PMID- 8290540
TI  - [Prof. V. G. Shtefko--outstanding scientist and phthisiologist].

PMID- 8290541
TI  - [The complex assessment of the health status of children in the early period of
      primary tuberculous infection taking health groups into account].
AB  - Children belonging to different health groups aged 4-14 (n = 350) with a turn in
      tuberculin reactions were examined for a relation of their health status to the
      onset, course and chemotherapy outcomes of early tuberculous infection. Health
      groups 3 and 4 appeared risk factors by a turn in tuberculin reactions. An
      inverse relationship was revealed between children's health and their immune
      status, whereas general condition of the examinees and efficacy of their
      chemotherapy correlated directly.

PMID- 8290542
TI  - [Deficiencies in the early detection of pulmonary tuberculosis and the
      possibilities for their elimination].
AB  - The investigation into the causes of late detection of pulmonary tuberculosis
      involving scrutiny of case records, data on new-onset cases, follow-up, protocols
      on the analysis of missed diagnoses has been performed for 772 cases registered
      in the Vinnitsa region through 1989-1991. The authors came to the conclusion that
      the shortcomings revealed in tuberculosis detection are primarily due to:
      violation of standard requirements as regards identification of primary
      tuberculosis; insufficient alertness of general practitioners related to possible
      tuberculosis; low quality of fluorographic examinations, unsatisfactory
      examinations of subjects suffering from chronic nonspecific pulmonary diseases,
      chronic alcoholics, diabetics, gastroduodenal ulcer patients; radiation hazards.

PMID- 8290543
TI  - Transcription factors in inner ear development.

PMID- 8290544
TI  - Antigen-specific immunotherapy: is it a real possibility to combat T-cell
      mediated autoimmunity?

PMID- 8290545
TI  - Alpha and beta thyroid hormone receptor (TR) gene expression during auditory
      neurogenesis: evidence for TR isoform-specific transcriptional regulation in
      vivo.
AB  - Clinicians have long recognized that congenital deficiency of iodine (a component
      of thyroid hormone) somehow damages the human embryonic nervous system, causing
      sensori-neural deafness. Recently, a deletion encompassing most of the human beta
      thyroid hormone receptor (TR beta) gene has been found in children who are
      neurologically normal except for one striking defect: profound sensori-neural
      deafness. We now show that the TR beta gene is prominently expressed very early
      in rat inner ear development. This expression is remarkable because both TR beta
      1 and TR beta 2 mRNAs are restricted, as early as embryonic day 12.5, to that
      portion of the embryonic inner ear that gives rise to the cochlea, the structure
      responsible for converting sound into neural impulses. The timing of this
      expression, when correlated with human inner ear development, raises the
      possibility that TRs may act in human ontogenesis earlier than previously
      suspected. These results provide a rare correlation between a specific human
      neurologic deficit (deafness) and transcription factor expression in a highly
      discrete embryonic cell population (ventral otocyst). TR alpha gene expression is
      also prominent in the developing cochlea, but, in contrast to the restricted
      pattern of TR beta gene expression, TR alpha 1 and TR alpha 2 transcripts are
      also found in inner ear structures responsible for balance. Deafness in children
      homozygous for a large deletion in the TR beta gene suggests that cochlear alpha
      1 TRs cannot functionally compensate for the absence of TR beta 1 and TR beta 2.
      The developing inner ear may, therefore, represent an example of TR isoform
      specific transcriptional regulation in vivo.

PMID- 8290546
TI  - Peptide-induced T-cell tolerance to prevent autoimmune diabetes in a transgenic
      mouse model.
AB  - A synthetic peptide corresponding to an immunodominant epitope of lymphocytic
      choriomeningitis virus glycoprotein (LCMV GP) was used to prime or to tolerize
      CD8+ T cells in vivo, dependent on mode of immunization. Peptide-specific
      tolerance was then examined in transgenic mice expressing LCMV GP in the beta
      islet cells of the pancreas; these mice develop CD8+ T-cell-mediated diabetes
      within 8-14 days after LCMV infection. Specific peptide-induced tolerance
      prevented autoimmune destruction of beta islet cells and diabetes in this
      transgenic mouse model.

PMID- 8290547
TI  - Staphylococcal nuclease folding intermediate characterized by hydrogen exchange
      and NMR spectroscopy.
AB  - Pulsed hydrogen-deuterium exchange during refolding was used to probe the
      protection of backbone amide hydrogens from solvent exchange of the
      staphylococcal nuclease Pro117-->Gly variant. The extent of exchange for 39
      residues was determined by two-dimensional proton NMR after refolding for 5 ms to
      10 s. Three kinetic phases are inferred. Modest protection of amides in the early
      refolding intermediate composed of two beta-sheets formed by local sequence
      interactions was observed after a 5-ms refolding period. Protection factors were
      determined by varying the high pH labeling pulse after refolding for 100 ms. The
      intermediate state has modest, yet significant, protection for residues in the
      beta-sheets (protection factors of 10-60) and almost no protection in the alpha
      helices (protection factors of < 10). The pattern of labeling is consistent with
      a role for beta-turns and beta-hairpins in the formation of the early
      intermediate.

PMID- 8290548
TI  - Identification of an essential serine residue in glucagon: implication for an
      active site triad.
AB  - Several glucagon analogs containing substitutions for serine have been
      synthesized to assess the role of the four serine residues in the hormone. The
      strategic importance of His1 has been confirmed, and we have previously
      identified an aspartic acid critical for activity at position 9. While these
      findings have led to a series of pure glucagon antagonists, the details of
      specific glucagon-receptor interactions that switch on the ensuing signaling
      events are still not readily apparent. The requirement for serine was tested by
      the chemical synthesis of a series of analogs containing substitutions for the
      hydrophilic hydroxyl group in each of the highly conserved serine residues at
      positions 2, 8, 11, and 16 of glucagon. The resulting analogs were analyzed in
      rat hepatocyte membranes for their receptor-binding affinities as well as their
      abilities to stimulate adenylate cyclase. Positions 2 and 8 were the most
      sensitive to modification, where both binding and activity were adversely
      affected. This is consistent with the notion that although the sequence
      responsible for transduction lies in the amino-terminal half of glucagon, some
      residues at that end also contribute to binding affinity. Modifications at
      position 11 generated high-binding-affinity derivatives that were full or
      moderate agonists. In contrast, position 16 replacement analogs maintained
      significant receptor binding affinities while the agonist properties were almost
      completely lost, thus separating binding and transduction functions. Therefore,
      Ser16 is a third critical residue that determines glucagon activity. It is
      postulated, but not proven, that a serine residue, together with His1 and Asp9,
      may participate in the putative active center of glucagon, which, upon initial
      recognition and binding to receptor, leads to transduction of the biological
      signal. A dependence of the glucagon action on a three-residue cooperative
      mechanism might be analogous to the charge-relay scheme of serine proteases. It
      is suggested that, after binding to its receptor, glucagon becomes activated and
      functions like a coenzyme in catalyzing the specific hydrolysis of a peptide bond
      in the receptor, generating new amino and carboxyl end groups, and that one of
      these exposed chains may contact the GTP-binding protein and activate it for
      further interaction with adenylate cyclase. This idea was supported by inhibition
      experiments with 4-amidinophenylmethanesulfonyl fluoride (APMSF), a specific and
      irreversible inhibitor of serine proteases, which at a concentration of 5 mM
      completely suppressed cAMP formation by glucagon in liver membranes. cAMP
      formation was not affected if either glucagon or membranes were separately
      pretreated with APMSF and then assayed.

PMID- 8290549
TI  - Ribosomal gene promoter domains can function as artificial enhancers of RNA
      polymerase I transcription, supporting a promoter origin for natural enhancers in
      Xenopus.
AB  - Enhancers of RNA polymerase I transcription in higher eukaryotes are repetitive
      elements within the intergenic spacers of rRNA genes. In Xenopus and mouse,
      enhancers and the gene promoter bind the activator protein, upstream binding
      factor, and in Xenopus, enhancers also share sequence similarity with an upstream
      domain of the promoter. This upstream promoter domain can act as an efficient
      enhancer when polymerized and cloned adjacent to a ribosomal gene promoter
      injected into oocytes. A core promoter domain lacking similarity with spacer
      sequences in Xenopus laevis but analogous to a repeated sequence in Xenopus
      borealis can also function as an enhancer. These data demonstrate functional
      relatedness between the promoter and enhancers, supporting the hypothesis that
      enhancers could have evolved from duplicated promoter domains that bind essential
      transcription factors. The ability of upstream binding factor to bind enhancers
      inactivated by mutation suggests that upstream binding factor binding alone
      cannot explain enhancer function.

PMID- 8290550
TI  - The alpha/beta sheath and its cytoplasmic tyrosines are required for signaling by
      the B-cell antigen receptor but not for capping or for serine/threonine-kinase
      recruitment.
AB  - The B-cell antigen receptor is composed of membrane immunoglobulin sheathed by an
      alpha/beta heterodimer. The complex is noncovalently associated with protein
      kinase activity, and crosslinking of the receptor leads to capping and
      transmembrane signaling. Here we show that the sheath is not necessary either for
      this capping or for the association of membrane immunoglobulin with the detergent
      insoluble cytoskeletal fraction that occurs following crosslinking. It is also
      not required for association of membrane immunoglobulin with a casein-kinase-like
      serine/threonine kinase. The sheath is essential, however, for transmembrane
      signaling. Provision of just the cytoplasmic domain of the beta sheath
      polypeptide to a mutant, unsheathed IgM molecule was sufficient to restore full
      signaling capability as judged by the phosphorylation of a variety of cellular
      proteins, including the B-cell-specific transmembrane protein CD22. This
      signaling was destroyed by mutating one of the tyrosines in the beta cytoplasmic
      domain. These results not only suggest that receptor signaling is mediated
      through phosphorylation of the tyrosines in the sheath's cytoplasmic domains but,
      together with previous work, indicate that different motifs within the sheath
      mediate presentation and signaling.

PMID- 8290552
TI  - A cytolysin encoded by Salmonella is required for survival within macrophages.
AB  - A Salmonella gene encoding a cytolysin has been identified by screening for
      hemolysis on blood agar. DNA sequence analyses together with genetic mapping in
      Salmonella suggest that it is unrelated to other toxins or hemolysins. The gene
      (slyA) is present in every strain of Salmonella examined, in Shigella, and in
      enteroinvasive Escherichia coli but not in other Enterobacteriaceae. SlyA
      (salmolysin) purified from a derivative of the original clone has hemolytic and
      cytolytic activity and has a molecular weight predicted by the DNA sequence. The
      median lethal dose and infection kinetics in mice suggest that the toxin is
      required for virulence and facilitates Salmonella survival within mouse
      peritoneal macrophages.

PMID- 8290551
TI  - Differential expression of two fibroblast growth factor-receptor genes is
      associated with malignant progression in human astrocytomas.
AB  - Malignant astrocytomas, which are highly invasive, vascular neoplasms, compose
      the majority of nervous system tumors in humans. Elevated expression of
      fibroblast growth factors (FGFs) in astrocytomas has implicated the FGF family of
      mitogens in the initiation and progression of astrocyte-derived tumors. In this
      study, we demonstrated that human astrocytomas undergo parallel changes in FGF
      receptor (FGFR) expression during their progression from a benign to a malignant
      phenotype. FGFR type 2 (BEK) expression was abundant in normal white matter and
      in all low-grade astrocytomas but was not seen in malignant astrocytomas.
      Conversely, FGFR type 1 (FLG) expression was absent or barely detectable in
      normal white matter but was significantly elevated in malignant astrocytomas.
      Malignant astrocytomas also expressed an alternatively spliced form of FGFR-1
      (FGFR-1 beta) containing two immunoglobulin-like disulfide loops, whereas normal
      human adult and fetal brains expressed a receptor form (FGFR-1 alpha) containing
      three immunoglobulin-like disulfide loops. Intermediate grades of astrocytic
      tumors exhibited a gradual loss of FGFR-2 and a shift in expression from FGFR-1
      alpha to FGFR-1 beta as they progressed from benign to malignant phenotype. These
      results suggest that differential expression and alternative splicing of FGFRs
      may be critical in the malignant progression of astrocytic tumors.

PMID- 8290553
TI  - Envelope glycoprotein gp120 of human immunodeficiency virus type 1 alters ion
      transport in astrocytes: implications for AIDS dementia complex.
AB  - Infection by human immunodeficiency virus type 1 (HIV-1) is often complicated by
      a variety of neurological abnormalities. The most common clinical syndrome,
      termed acquired immunodeficiency syndrome (AIDS) dementia complex, presents as a
      subcortical dementia with cognitive, motor, and behavioral disturbances and is
      unique to HIV-1 infection. The pathogenesis of this syndrome is poorly understood
      but is believed to involve interactions among virally infected
      macrophages/microglia, astrocytes, and neurons. In this study, we show that
      exposure of primary rat and human astrocytes to heat-activated HIV-1 virions, or
      to eukaryotically expressed HIV-1 and HIV-2 envelope glycoproteins (gp120)
      stimulates amiloride-sensitive Na+/H+ antiport, potassium conductance, and
      glutamate efflux. These effects are blocked specifically by amiloride, an
      inhibitor of Na+/H+ antiport and by the selective removal of gp120 with
      immobilized monoclonal antibody. As a result of modulation of astrocytic function
      by gp120, the ensuing neuronal depolarization and glutamate exposure could
      activate both voltage-gated and N-methyl-D-aspartate-regulated Ca2+ channels,
      leading to increases in intraneuronal Ca2+ and neuronal death. These findings
      implicate the astrocyte directly in the pathogenesis of AIDS dementia complex.

PMID- 8290554
TI  - G proteins of the G12 family are activated via thromboxane A2 and thrombin
      receptors in human platelets.
AB  - Using subtype-specific antisera, we were able to identify the recently described
      alpha subunits of G12 and G13 in platelet membranes as 43-kDa proteins.
      Activation of the thromboxane A2 and the thrombin receptors in platelet membranes
      led to increased incorporation of the photoreactive GTP analogue [alpha-32P]GTP
      azidoanilide into immunoprecipitated alpha 12 and alpha 13, indicating that both
      receptors couple to G12 and G13. In addition, both activated receptors were
      demonstrated to couple to one or more members of the Gq family. In the absence of
      receptor agonists, incorporation of [alpha-32P]GTP azidoanilide into alpha 12 and
      alpha 13 was low over a long time period (up to 45 min) due to an obviously low
      basal nucleotide exchange rate, whereas an agonist-stimulated photolabeling of
      alpha 12 and alpha 13 could be observed after 4-8 min and reached a maximum after
      30-45 min. Effective activation of G12 and G13 via the thromboxane A2 and the
      thrombin receptors was not dependent on the presence of GDP. Our results provide
      evidence that G12 and G13 play a functional role in transmembrane signal
      transduction and suggest that both proteins are involved in pathways leading to
      platelet activation.

PMID- 8290555
TI  - The parasitophorous vacuole membrane surrounding intracellular Toxoplasma gondii
      functions as a molecular sieve.
AB  - The obligate intracellular protozoan parasite Toxoplasma gondii creates and
      enters into a unique membrane-bounded cytoplasmic compartment, the
      parasitophorous vacuole, when invading mammalian host cells. By microinjecting
      polar fluorescent molecules into individual T. gondii-infected fibroblasts, we
      show here that the parasitophorous vacuole membrane (PVM) surrounding the
      parasite functions as a molecular sieve. Lucifer yellow (457 Da) displayed free
      bidirectional flux across the PVM and distinctly outlined the parasites, which
      did not take up the dye, within the vacuole. This dye movement was not
      appreciably delayed by pretreatment of cells with 5 mM probenecid or chilling the
      monolayer to 5 degrees C, suggesting that dye movement was due to passive
      permeation through a membrane pore rather than active transport. Calcein, fluo-3,
      and a series of fluorescein isothiocyanate-labeled peptides up to 1291 Da crossed
      the PVM in a size-restricted fashion. A labeled peptide of 1926 Da and labeled
      dextrans and proteins (> or = 3000 Da) failed to transit the PVM. This putative
      channel in the PVM therefore allows exchange of molecules up to 1300-1900 Da
      between the host cell cytoplasm and the parasitophorous vacuolar space.

PMID- 8290556
TI  - Somatic diversification in the heavy chain variable region genes expressed by
      human autoantibodies bearing a lupus-associated nephritogenic anti-DNA idiotype.
AB  - Monoclonal anti-DNA antibodies bearing a lupus nephritis-associated idiotype were
      derived from five patients with systemic lupus erythematosus (SLE). Genes
      encoding their heavy (H)-chain variable (VH) regions were cloned and sequenced.
      When compared with their closest VH germ-line gene relatives, these sequences
      exhibit a number of silent (S) and replacement (R) substitutions. The ratios of
      R/S mutations were much higher in the complementarity-determining regions (CDRs)
      of the antibodies than in the framework regions. Molecular amplification of
      genomic VH genes and Southern hybridization with somatic CDR2-specific
      oligonucleotide probes showed that the configuration of the VH genes
      corresponding to VH sequences in the nephritogenic antibodies is not present in
      the patient's own germ-line DNA, implying that the B-cell clones underwent
      somatic mutation in vivo. These findings, together with the characteristics of
      the diversity and junctional gene elements utilized to form the antibody,
      indicate that these autoantibodies have been driven through somatic selection
      processes reminiscent of those that govern antibody responses triggered by
      exogenous stimuli.

PMID- 8290557
TI  - Cardiac and skeletal myopathy in beta myosin heavy-chain simian virus 40 tsA58
      transgenic mice.
AB  - The mechanisms regulating cardiac muscle differentiation and development are
      incompletely understood. To examine the relationships between cardiocyte
      proliferation and differentiation, we tested the ability of a fragment from the
      rat beta myosin heavy-chain (MHC beta) gene to correctly target expression of a
      thermolabile simian virus 40 large tumor antigen allele (tsA58) in the developing
      mouse. Transgene expression in the heart was observed as early as 10 days
      postconception and was developmentally regulated in parallel with the endogenous
      MHC beta gene. Expression was also detected in developing skeletal muscle,
      although at low levels. Despite the temperature sensitivity of the mutant large
      tumor antigen protein, a subset of transgenic mice in several lineages developed
      marked cardiac and skeletal myopathies.

PMID- 8290558
TI  - Detection of nondisjunction and recombination in meiotic and postmeiotic cells
      from XYSxr [XY,Tp(Y)1Ct] mice using multicolor fluorescence in situ
      hybridization.
AB  - Current meiotic dogma holds that synapsis is required for recombination and that
      recombination is required for proper disjunction. The mouse chromosome aberration
      XYSxr [sex reversal; redesignated XY,Tp(Y)1Ct] appears to challenge this
      assumption, for although chromosomes X and Y often fail to synapse and recombine,
      there is no dramatic increase in aneuploid progeny. An explanation of this
      conundrum might be that X-Y univalent spermatocytes do not survive. The phenotype
      of sex reversal is generated by the "obligatory" crossover between the X and Y
      chromosomes, which always occurs proximal to a duplicated copy of the testis
      determining gene Sry and transfers one copy from one chromatid of the Y
      chromosome to one chromatid of the X. Animals that inherit an X chromosome with
      the Sry gene are chromosomally female but phenotypically male. We have used
      fluorescence in situ hybridization (FISH) to visualize probes for the X and Y
      chromosomes and for the Sry sequence and chromosome 8 to track the fate of both
      recombinant and nonrecombinant chromosomes through metaphases I and II into
      spermatids and sperm. In the 219 gametes examined by multicolor FISH, the
      frequency of aneuploid products (XY or "O") was low (3.7%) despite a high
      frequency (66%) of X-Y separation at metaphase I. In balanced gametes, X and Y
      recombinant chromosomes slightly exceeded nonrecombinants. Both of these
      observations support the earlier proposal that asynapsis and nondisjunction in
      primary spermatocytes lead to their developmental arrest and degeneration.

PMID- 8290559
TI  - Progesterone and RU486: opposing effects on human sperm.
AB  - Progesterone induced a rapid influx of calcium in capacitated human sperm,
      followed by a long-lasting, dose-dependent increase of intracellular free
      calcium. Thereafter, progesterone increased the fraction of hyperactivated sperm
      and the acrosome reaction. On the contrary, the progesterone antagonist RU486
      (mifepristone) induced an immediate and transient, dose-dependent decrease of
      intracellular free calcium and a drop in the values of sperm movement parameters
      related to hyperactivation. Moreover, RU486 counteracted the effects of
      progesterone on calcium influx, lateral sperm head displacement, and the acrosome
      reaction. Therefore, RU486 effects were opposite to those of progesterone. The
      nature of the membrane receptor(s) involved is unknown. Several steroids bearing
      11 beta-phenyl substitutions, with different pharmacological profiles, were also
      investigated. It was concluded that the steroid structure and chemical groups
      added to the 11 beta-phenyl influence effects on calcium influx.

PMID- 8290560
TI  - Internal Ca2+ mobilization is altered in fibroblasts from patients with Alzheimer
      disease.
AB  - The recent demonstration of K+ channel dysfunction in fibroblasts from Alzheimer
      disease (AD) patients and past observations of Ca(2+)-mediated K+ channel
      modulation during memory storage suggested that AD, which is characterized by
      memory loss and other cognitive deficits, might also involve dysfunction of
      intracellular Ca2+ mobilization. Bombesin-induced Ca2+ release, which is inositol
      trisphosphate-mediated, is shown here to be greatly enhanced in AD fibroblasts
      compared with fibroblasts from control groups. Bradykinin, another activator of
      phospholipase C, elicits similar enhancement of Ca2+ signaling in AD fibroblasts.
      By contrast, thapsigargin, an agent that releases Ca2+ by direct action on the
      endoplasmic reticulum, produced no differences in Ca2+ increase between AD and
      control fibroblasts. Depolarization-induced Ca2+ influx data previously
      demonstrated the absence of between-group differences of Ca2+ pumping and/or
      buffering. There was no correlation between the number of passages in tissue
      culture and the observed Ca2+ responses. Furthermore, cells of all groups were
      seeded and analyzed at the same densities. Radioligand binding experiments
      indicated that the number and affinity of bombesin receptors cannot explain the
      observed differences. These and previous observations suggest that the
      differences in bombesin and bradykinin responses in fibroblasts and perhaps other
      cell types are likely to be due to alteration of inositol trisphosphate-mediated
      release of intracellular Ca2+.

PMID- 8290561
TI  - Function of major histocompatibility complex class II promoters requires
      cooperative binding between factors RFX and NF-Y.
AB  - Transcription of major histocompatibility complex (MHC) class II genes is
      controlled largely by the conserved promoter elements called the X and Y boxes.
      We show here that RFX, the X box-binding protein deficient in certain MHC class
      II-deficient immunodeficiency patients (CID), and the Y box-binding protein NF-Y
      bind cooperatively. Functional relevance of this protein-protein interaction is
      suggested by the fact that promoter activity correlates with cooperative binding
      of RFX and NF-Y rather than with binding of RFX or NF-Y alone. Stability of the
      RFX/NF-Y complex is affected by alterations in X-Y box spacing. These results are
      consistent with the fact that MHC class II promoter function is dependent on
      correct stereospecific alignment of the X and Y boxes. Cooperative binding
      involving RFX, NF-Y, and perhaps other MHC class II promoter-binding proteins may
      explain why the highly specific defect in binding of RFX observed in CID cells is
      associated in vivo with a bare promoter in which all of the cis-acting elements,
      including the X and Y boxes, are unoccupied.

PMID- 8290562
TI  - Phospholipase C-gamma 1 binding to intracellular receptors for activated protein
      kinase C.
AB  - Phospholipase C-gamma 1 (PLC-gamma 1; EC 3.1.4.11) hydrolyzes
      phosphatidylinositol 4,5-bisphosphate to generate diacylglycerol and inositol
      1,4,5-trisphosphate and is activated in response to growth factor stimulation and
      tyrosine phosphorylation. Concomitantly, the enzyme translocates from the cytosol
      to the particulate cell fraction. A similar process of activation-induced
      translocation from the cytosol to the cell particulate fraction has also been
      described for protein kinase C (PKC). We have previously shown that activated PKC
      binds to specific receptor proteins, receptors for activated C kinase, or RACKs,
      of approximately 30 kDa. Here, we show that PLC-gamma 1 bound to these RACKs and
      inhibited subsequent PKC binding to RACKs. However, unlike PKC, the binding of
      PLC-gamma 1 to RACKs did not require phospholipids and calcium. After epidermal
      growth factor treatment of intact A-431 cells, the binding of PLC-gamma 1 to
      RACKs increased as compared with PLC-gamma 1 from control cells. This increase in
      PLC-gamma 1 binding to RACKs was due to the phosphorylation of PLC-gamma 1.
      Additional data indicated that PLC-gamma 1 binds to RACKs in solution; epidermal
      growth factor receptor-dependent PLC-gamma 1 phosphorylation and activation
      decreased in the presence of RACKs. It is possible that, in vivo, PLC-gamma 1
      associates with RACKs or with other PLC-gamma 1-specific anchoring proteins in
      the particulate cell fraction. Since a PKC C2 homologous region is present in PLC
      gamma 1, the C2 region may mediate the activation-induced translocation of the
      enzyme to the cell particulate fraction and the anchoring protein-PLC-gamma 1
      complex may be the active translocated form of PLC-gamma 1.

PMID- 8290563
TI  - Regional, cellular, and ultrastructural distribution of N-methyl-D-aspartate
      receptor subunit 1 in monkey hippocampus.
AB  - The regional, cellular, and subcellular distributions of N-methyl-D-aspartate
      (NMDA) receptor subunit 1, NMDAR-1, were investigated in monkey hippocampus by
      using a monoclonal antibody directed against a fusion protein corresponding to aa
      660-811 of NMDAR-1. The data indicate that many neurons in each subfield of the
      hippocampus contain NMDAR-1 protein, although the intensity and distribution of
      immunoreactivity varied across regions, strata, and cellular compartments. In
      stratum lucidum of CA3, mossy fiber axons were immunoreactive for NMDAR-1, which
      may correspond to previously hypothesized presynaptic receptors. NMDAR-1-labeled
      postsynaptic profiles were present in stratum radiatum of CA3 but were largely
      absent from stratum lucidum. Such intraneuronal segregation of glutamate receptor
      subunits or classes may be spatially correlated with afferent systems that
      exhibit laminar segregation and terminate in different portions of the
      postsynaptic dendritic tree. For example, in CA3 pyramidal cells, NMDA receptors
      are postsynaptic in distal apical dendrites (stratum radiatum) where NMDA
      dependent long-term potentiation in rats is mediated by associational/commissural
      afferents, and are absent from proximal apical dendrites (stratum lucidum), where
      NMDA-independent long-term potentiation is mediated by the mossy fiber input.

PMID- 8290564
TI  - Double-stranded cleavage of pBR322 by a diiron complex via a "hydrolytic"
      mechanism.
AB  - Treatment of plasmid pBR322 with Fe2-(HPTB)(OH)(NO3)4(HPTB = N,N,N',N'-tetrakis(2
      benzimidazolylmethyl)-2-hydroxy-1,3-diaminopr opane) and H2O2 or O2 and a
      reductant (dithiothreitol or ascorbate) results in double-stranded cleavage of
      the plasmid. The linearization of supercoiled pBR322 by this complex is not
      inhibited by hydroxyl radical scavengers. On the other hand, the linearized
      pBR322 is efficiently religated by T4 DNA ligase, and the presence of 3'-OH and
      5'-OPO3 ends is corroborated by 3'- and 5'-end-labeling studies. These
      observations indicate that cleavage results from hydrolysis of the DNA-phosphate
      backbone, which is proposed to occur by nucleophilic attack of the bound peroxide
      on the phosphodiester. Double-stranded cleavage by the Fe2(HPTB)(OH)(NO3)4/H2O2
      adduct preferentially occurs between bp 3489 and 3485 of pBR322.

PMID- 8290565
TI  - The iron-responsive element-binding protein: localization of the RNA-binding site
      to the aconitase active-site cleft.
AB  - The iron-responsive element-binding protein (IRE-BP) binds to specific stem-loop
      RNA structures known as iron-responsive elements (IREs) present in a variety of
      cellular mRNAs (e.g., those encoding ferritin, erythroid 5-aminolevulinate
      synthase, and transferrin receptor). Expression of these genes is regulated by
      interaction with the IRE-BP. The IRE-BP is identical in sequence to cytosolic
      aconitase, and the function of the protein is determined by the presence or
      absence of an Fe-S cluster. The protein either functions as an active aconitase
      when the Fe-S cluster is present or as an RNA-binding protein when the protein
      lacks this cluster. Aconitase activity and IRE-binding activity are mutually
      exclusive, and interconversion between the two activities is determined by
      intracellular Fe concentrations. Mapping of the RNA-binding site of the IRE-BP by
      UV cross-linking studies defines a major contact site between IRE and protein in
      the active-site region. Modeling based on probable structural similarities
      between the previously crystallized mitochondrial aconitase and the IRE-BP
      predicts that these residues would be accessible to the IRE only were there a
      major change in the predicted conformation of the protein when cells are iron
      depleted.

PMID- 8290566
TI  - Reconstitution of functional human single-stranded DNA-binding protein from
      individual subunits expressed by recombinant baculoviruses.
AB  - Human single-stranded DNA-binding protein (HSSB), also known as replication
      protein A, is composed of a 70-kDa single-stranded DNA-binding subunit (p70) and
      34-kDa and 11-kDa (p34 and p11, respectively) subunits of unknown functions. We
      have examined interactions among the HSSB subunits in vivo by coinfecting insect
      cells with different combinations of recombinant baculoviruses encoding p70, p34,
      or p11. In vivo, coexpressed p34 and p11 subunits formed stable complexes,
      whereas neither p34 nor p11 formed stable complexes with p70. In cells coinfected
      with viruses expressing all three subunits, the stable heterotrimer formed,
      which, when purified, replaced HSSB isolated from HeLa cells in various assays,
      including simian virus 40 DNA replication in vitro. These data suggest that, in
      the assembly of functionally active HSSB, formation of the p34-p11 complex
      precedes p70 addition to the complex.

PMID- 8290567
TI  - Targeted disruption of metallothionein I and II genes increases sensitivity to
      cadmium.
AB  - We inactivated the mouse metallothionein (MT)-I and MT-II genes in embryonic stem
      cells and generated mice homozygous for these mutant alleles. These mice were
      viable and reproduced normally when reared under normal laboratory conditions.
      They were, however, more susceptible to hepatic poisoning by cadmium. This proves
      that these widely expressed MTs are not essential for development but that they
      do protect against cadmium toxicity. These mice provide a means for testing other
      proposed functions of MT in vivo.

PMID- 8290568
TI  - Functional analysis of myosin missense mutations in familial hypertrophic
      cardiomyopathy.
AB  - To analyze potential functional consequences of myosin heavy chain (MHC)
      mutations identified in patients with familial hypertrophic cardiomyopathy (FHC),
      we have assessed the stability of the mutant MHCs and their ability to form thick
      filaments. Constructs encoding wild-type rat alpha MHC and seven corresponding
      FHC missense mutants were transfected into COS cells. Immunoblot analysis
      suggested that FHC mutations do not grossly alter protein stability. Wild-type
      alpha MHC transfected into COS cells forms structures previously shown to be
      arrays of thick filaments, which also resemble myosin structures observed early
      in differentiation of muscle cells. Surprisingly, up to 29% of COS cells
      transfected with the FHC mutants failed to form filamentous structures. To assess
      whether this phenotype was specific for the FHC mutants and not generalizable to
      any myosin mutation, COS cells were transfected with a construct encoding an MHC
      with a 168-amino acid deletion of the hinge/rod region. This deletion construct
      formed filamentous structures with the same frequency as wild-type MHC.
      Biochemical analysis of one FHC mutant (Arg-249-->Gln) demonstrates that the
      structures formed by the mutant are solubilized at a lower ionic strength than
      those formed by wild-type MHC. We conclude that although the FHC mutant MHC is
      not labile, its assembly properties may be impaired.

PMID- 8290569
TI  - The B1C8 protein is in the dense assemblies of the nuclear matrix and relocates
      to the spindle and pericentriolar filaments at mitosis.
AB  - The B1C8 monoclonal antibody detects a 180-kDa nuclear matrix-specific protein.
      The protein is a component of the dense, metabolically active bodies or
      assemblies revealed by resinless section electron microscopy of the nuclear
      matrix. These assemblies are scattered through the nuclear interior, enmeshed in
      a complex network of 11-nm filaments. Resinless section electron microscopy of
      immunogold-stained nuclear matrix preparations shows B1C8 located in many but
      apparently not all the assemblies. In this regard, the B1C8 antigen resembles
      previously studied nuclear matrix proteins such as the H1B2 protein. The speckled
      pattern of nuclear immunofluorescence by B1C8 reflects this labeling of the dense
      assemblies in the nuclear matrix. Somewhat unusual is the faint staining of
      cytoplasmic microtubules by B1C8, which appears to be due to a weakly cross
      reacting protein. During cell division, the B1C8 antigen redistributed
      drastically, showing the dispersion of nuclear matrix assemblies at mitosis.
      Speckles of B1C8 fluorescence first coalesced at prophase within the nuclear
      interior and then scattered into numerous cytoplasmic speckles by prometaphase.
      At metaphase, the B1C8 speckled cytoplasmic staining had become even more widely
      distributed and finely grained. Also, intense labeling appeared at the mitotic
      pole and on the spindle fibers themselves. The reassembly of B1C8 antigens into
      larger cytoplasmic speckles began at anaphase and finally, at telophase, most
      B1C8 labeling redistributed into speckles in the re-forming nuclei.

PMID- 8290570
TI  - Cellular epigenetics: topochronology of progressive "spontaneous" transformation
      of cells under growth constraint.
AB  - Early passages of NIH 3T3 cells yield about 10 transformed foci for every 10(5)
      cells seeded after the cells multiply to confluence in a standardized 2-week
      assay. The question arose whether more cells would give rise to foci if given
      more time for their development. This question could not be answered simply by
      extending the incubation period, since the original foci spread to cover much of
      the area of the culture dish. Transformed cells can also detach into the medium
      from the original foci to initiate new foci by reattaching at a distance. These
      problems were averted by growing cells in multiwell plates which in effect
      simulated partitioned culture dishes. All the wells in a given plate were assayed
      for focus formation at successive intervals up to 14 weeks. The results indicated
      the spatial pattern and sequence of transformation on different parts of the
      "partitioned" dish. The number of multiwells containing focus-forming cells
      increased steadily with time, indicating that all parts of a dish eventually
      undergo transformation. Also, most of the transformations were recorded long
      after confluence in the multiwells was reached. Hence such a transformation is
      much more likely to occur in the nondividing state rather than in the dividing
      state of the cells and is thus inconsistent with a mutational basis. The results
      suggest that "spontaneous" transformation is a population-wide, epigenetic
      phenomenon. This agrees with the results from clonal analysis and other studies
      and is well described by the concept of progressive state selection, in which
      "spontaneous" transformation represents a heterogeneous, adaptive response of
      competent cells to moderate constraints on cell growth.

PMID- 8290571
TI  - Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation
      in JB6 mouse epidermal cells.
AB  - AP-1 transcriptional activity is stimulated by the transformation promoters
      phorbol 12-myristate 13-acetate ("12-O-tetradecanoylphorbol 13-acetate," TPA) and
      epidermal growth factor (EGF) in promotion-sensitive (P+) but not in promotion
      resistant (P-) JB6 mouse epidermal cell lines. Although TPA stimulates expression
      of the jun and fos family genes, only c-jun expression shows higher elevation in
      P+ cells than in P- cells. The present study tests the hypothesis that induced AP
      1 activity is required for tumor promoter-induced transformation in JB6 P+ cells.
      Both retinoic acid and the glucocorticoid fluocinolone acetonide inhibited basal
      and TPA-induced AP-1 activities that were tested with a stromelysin promoter
      chloramphenicol acetyltransferase reporter gene in P+ cells. Since both retinoic
      acid and fluocinolone acetonide are active in inhibiting TPA-induced anchorage
      independent transformation of P+ cells in the dose range that blocks TPA-induced
      AP-1 activity, their antipromoting effects may occur through inhibition of AP-1
      activity. To test the hypothesis with a more specific inhibitor, stable clonal
      transfectants of P+ cells expressing dominant negative c-jun mutant encoding a
      transcriptionally inactive product were analyzed. All transfectants showed a
      block in TPA and EGF induction of AP-1 activity. All transfectants also showed
      inhibition of TPA-induced transformation, and most transfectants showed a block
      in EGF-induced transformation. These results indicate that AP-1 activity is
      required for TPA- or EGF-induced transformation. This work demonstrates that a
      specific block in induced AP-1 activity inhibits tumor promoter-induced
      transformation.

PMID- 8290572
TI  - Chronic active hepatitis in transgenic mice expressing interferon-gamma in the
      liver.
AB  - Interferon-gamma may play an important role in the immune response and in
      inflammatory diseases, including chronic active hepatitis. To understand the role
      of interferon-gamma in the regulation of inflammation and to establish a mouse
      model of chronic active hepatitis, we produced transgenic mice in which the mouse
      interferon-gamma gene was regulated by a liver-specific promoter, the serum
      amyloid P component gene promoter. Four transgenic mouse lines were generated,
      and two of these lines expressed mRNA of interferon-gamma in the liver. Levels of
      serum transaminases increased gradually as a function of age and were
      significantly higher than those of interferon-gamma-negative littermates after 4
      weeks after birth. One transgenic mouse line showed a histology of chronic active
      hepatitis similar to that found in human patients, although cirrhotic changes
      such as fibrosis were scarce. Thus, the liver-specific production of interferon
      gamma is sufficient to induce chronic inflammatory disease and this mouse is a
      transgenic model of chronic active hepatitis.

PMID- 8290573
TI  - The polymorphic subtelomeric regions of Plasmodium falciparum chromosomes contain
      arrays of repetitive sequence elements.
AB  - The human malaria parasite Plasmodium falciparum exhibits a high degree of
      chromosomal polymorphism, which may contribute to its ability to evade host
      defenses. The analysis of parasite chromosomes has revealed that these
      polymorphisms are confined to the subtelomeric regions, which are
      transcriptionally silent and contain repetitive sequence elements. Several
      subtelomeric repetitive elements have been isolated and mapped by using P.
      falciparum yeast artificial chromosome (YAC) clones. Structural analysis of
      parasite telomeric and subtelomeric YAC clones demonstrated that these repetitive
      elements are conserved between P. falciparum chromosome ends. We suggest that
      these subtelomeric elements promote chromosome pairing in P. falciparum and
      facilitate meiotic recombination and gene conversion between telomere-proximal
      genes.

PMID- 8290574
TI  - Molecular basis of cardiac potassium channel stimulation by protein kinase A.
AB  - Cardiac beta-adrenergic receptors accelerate heart rate by modulating ionic
      currents through a pathway involving cyclic AMP-dependent protein kinase A (PKA).
      Previous studies have focused on the regulation of Ca2+ channels by PKA; however,
      due to the heterogeneity of K+ channels expressed within the heart, little is
      known about the mechanism by which PKA modulates individual K+ channels. Here we
      report that PKA strongly enhanced the activity of a cloned delayed rectifier K+
      channel that is normally expressed in cardiac atria. This effect required a
      single PKA consensus phosphorylation site located near the amino terminus of the
      channel protein. Furthermore, patch clamp analysis revealed that PKA
      phosphorylation increased the open time that single channels spend in higher
      conductance states. These studies provide evidence that hormonal modulation of a
      cardiac K+ channel involves direct phosphorylation by PKA.

PMID- 8290575
TI  - Evidence for RNA editing in mitochondria of all major groups of land plants
      except the Bryophyta.
AB  - RNA editing has been documented in mitochondria of higher plants, notably dicots
      and monocots. To determine the distribution of mitochondrial RNA editing in the
      plant kingdom, we have now undertaken a survey of evolutionarily distant plants.
      RNA editing occurs in all major groups of land plants except the Bryophyta,
      suggesting that this process is an ancient trait that was established before the
      radiation of kormophyte plants. No editing is observed in representatives of the
      green algae, suggesting that editing arose in early land plants after the split
      of the Bryophyta or has been lost selectively in both algae and mosses. In ferns
      several U-->C changes are observed, one of which eliminates a genomically encoded
      UAA termination codon and creates a functional open reading frame.

PMID- 8290576
TI  - Identification of dynamin 2, an isoform ubiquitously expressed in rat tissues.
AB  - Dynamin is a 100-kDa microtubule-activated GTPase originally isolated from
      mammalian brain that has been proposed to be crucial in the early steps of
      endocytosis. Previous studies on the primary structure, biochemical properties,
      and functional role of dynamin indicated that it was neuron-specific. However,
      using an antibody against a synthetic peptide representing an enzymatic region of
      rat brain dynamin (D100), we identified a 100-kDa protein doublet in rat liver,
      suggesting that dynamin exists as different isoforms that are distinct from the
      brain counterpart. We then initiated a search for distinctive dynamin isoforms
      with antibodies and cDNA probes. A 500-bp PCR-generated cDNA probe corresponding
      to the enzymatic region of the rat brain dynamin-encoding gene was used to
      isolate six overlapping clones from a rat liver cDNA library that together span
      the complete coding sequence of another dynamin gene, "Dyn2." Sequence analyses
      reveal that dynamin 2 (Dyn2) is 75% identical to brain dynamin at the DNA level
      and is 79% identical at the protein level. By Northern blot analysis and isoform
      specific PCR, Dyn2 was found ubiquitously in adult rat tissues as two transcripts
      of 3.5 kb and 4 kb; the highest levels were found in testis. These results
      indicate that dynamin proteins are encoded by at least two genes expressed
      differentially in mammalian tissues and that the expression of Dyn2, and not of
      brain dynamin, accounts for the ubiquitous distribution of dynamin in rat
      tissues.

PMID- 8290577
TI  - Development of transforming function during transduction of proto-ras into Harvey
      sarcoma virus.
AB  - Oncogenic retroviruses are generated by transduction of the coding region of a
      protooncogene and acquire genetic changes during subsequent replication. Critical
      genetic events which occurred during and after transduction of rat proto-ras-1Ha
      into Harvey sarcoma virus were identified by evaluating the transforming activity
      of plausible synthetic progenitor proviruses encompassing the complete proto-ras
      genomic region with or without various 5' deletions. All progenitor proviruses
      induced phenotypic transformation of mouse NIH 3T3 cells, although with a 5- to
      10-fold lower frequency than Harvey sarcoma provirus. Although no tumor formation
      was observed in vivo after inoculation in the absence of helper murine
      retrovirus, both wild-type and progenitor viruses inoculated in the presence of
      helper virus induced tumors in newborn BALB/c mice. No critical alterations of
      the p21ras coding region and no deletion of 5' genomic elements were detected in
      a progenitor virus encompassing the complete proto-ras genomic region that had
      been isolated from tumors. However, one progenitor virus that included all proto
      ras exons induced tumors with a decreased latency. This virus contained a
      mutation in codon 12 (glycine to valine), which had apparently been selected
      during tumorigenesis in vivo. During the genesis of Harvey sarcoma virus,
      critical steps conferring transforming function are therefore transduction of
      coding proto-ras exons and enhancement of their transforming function by specific
      amino acid changes in p21ras.

PMID- 8290578
TI  - The RNA of RNase MRP is required for normal processing of ribosomal RNA.
AB  - We have isolated clones which complement the temperature sensitivity and abnormal
      rRNA processing pattern of the rrp2-2 mutant of Saccharomyces cerevisiae we
      previously described. DNA sequencing and restriction analysis demonstrated that
      all clones contain the NME1 gene encoding the RNA of the ribonucleprotein
      particle RNase MRP. Deletion analysis showed that the NME1 gene is responsible
      for the complementation of the rrp2-2 phenotype. A single base change was
      identified in the nme1 gene in the rrp2 mutant, confirming that the RRP2 and NME1
      genes are identical. Our experiments therefore indicate that RNase MRP, in
      addition to its previously reported role in formation of RNA primers for
      mitochondrial DNA replication [Clayton, D. A. (1991) Trends Biochem. Sci. 16, 107
      111], is involved in rRNA processing.

PMID- 8290579
TI  - Tat-mediated delivery of heterologous proteins into cells.
AB  - The Tat protein of human immunodeficiency virus 1 (HIV-1) can enter cells
      efficiently when added exogenously in tissue culture. To assess if Tat can carry
      other molecules into cells, we chemically cross-linked Tat peptides (residues 1
      72 or 37-72) to beta-galactosidase, horseradish peroxidase, RNase A, and domain
      III of Pseudomonas exotoxin A (PE) and monitored uptake colorimetrically or by
      cytotoxicity. The Tat chimeras were effective on all cell types tested, with
      staining showing uptake into all cells in each experiment. In mice, treatment
      with Tat-beta-galactosidase chimeras resulted in delivery to several tissues,
      with high levels in heart, liver, and spleen, low-to-moderate levels in lung and
      skeletal muscle, and little or no activity in kidney and brain. The primary
      target within these tissues was the cells surrounding the blood vessels,
      suggesting endothelial cells, Kupffer cells, and/or splenic macrophages. Tat
      mediated uptake may allow the therapeutic delivery of macromolecules previously
      thought to be impermeable to living cells.

PMID- 8290580
TI  - Waves and stimulus-modulated dynamics in an oscillating olfactory network.
AB  - The temporal dynamics of electrical activity in an olfactory organ, the
      procerebral lobe of the terrestrial mollusc Limax maximus, is studied. The lobe
      exhibits intrinsic oscillations in its field potential. Intracellular recordings
      show that the lobe contains two classes of neurons, both with activity phase
      locked to the oscillation. Neurons in one class produce periodic bursts of spikes
      while those in the other class fire infrequently but receive strong, periodic
      inhibition whose onset coincides with the burst. The large-scale activity of
      these neurons is imaged in preparations stained with voltage-sensitive dyes. We
      observe waves of electrical activity that span the width of the lobe and travel
      its full length along a longitudinal axis. Simultaneous optical and intracellular
      recordings show that the form of the wave reflects the electrical activity of
      both classes of neurons. The application of natural odor stimuli causes the
      electrical activity along the lobe to transiently switch from the state with
      propagating waves to one with spatially uniform oscillations. The behavioral and
      computational relevance of this change in global timing is discussed.

PMID- 8290581
TI  - Monoclonal antibodies to nerve growth factor affect the postnatal development of
      the visual system.
AB  - Exogenous supply of nerve growth factor (NGF) prevents the effects of monocular
      deprivation. This suggests that visual afferents may be competing for an
      endogenous neurotrophic factor, related to NGF, whose production by postsynaptic
      cells depends on the activity of afferent fibers. To test the hypothesis that
      endogenous NGF may play a role in the functional and anatomical development of
      the rat geniculo cortical system, the physiological action of NGF in the rat
      visual system was antagonized by using two independent monoclonal antibodies
      which neutralize NGF (alpha D11 and 4C8). To provide a continuous supply of
      antibodies during the period of visual cortical plasticity, alpha D11 or 4C8
      antibody-producing hybridoma cells were implanted in the lateral ventricle of
      rats at postnatal day 15. This resulted in dramatic alterations of two of the
      most important parameters characterizing the functional development of the visual
      system, namely, visual acuity and binocularity of cortical neurons and in
      shrinkage of cells in the lateral geniculate nucleus. This demonstrates that the
      action of endogenous NGF is necessary for the normal functional and anatomical
      development of the geniculocortical system.

PMID- 8290582
TI  - Photoaffinity labeling of Arabidopsis thaliana plasma membrane vesicles by 5
      azido-[7-3H]indole-3-acetic acid: identification of a glutathione S-transferase.
AB  - We used 5-azido-[7-3H]indole-3-acetic acid (5-azido-[7-3H]IAA), a photoaffinity
      analogue of the plant hormone indole-3-acetic acid (IAA), to search for auxin
      binding proteins in Arabidopsis thaliana membranes. We identified an auxin
      binding protein with a molecular mass of 24 kDa (Atpm24) in microsomes as well as
      in plasma membrane vesicles. Atpm24 was solubilized by 1% Triton X-100 and
      partially purified. A cDNA clone (Atpm24.1) corresponding to Atpm24 was isolated.
      The amino acid sequence predicted from the Atpm24.1 cDNA contains 212 amino acid
      residues with a relative molecular mass of 24,128 Da. Data base searches revealed
      that the predicted protein has homology to glutathione S-transferases (GSTs; EC
      2.5.1.18). When Atpm24.1 was expressed in Escherichia coli, we found a high level
      of GST activity in the bacterial extracts. We have analyzed the substrate
      specificity of this protein and found that cumene hydroperoxide and trans
      stilbene oxide but not trans-cinnamic acid or IAA-CoA were substrates. A role for
      this GST in physiological processes of plants is discussed.

PMID- 8290583
TI  - Agrobacterium T-strand production in vitro: sequence-specific cleavage and 5'
      protection of single-stranded DNA templates by purified VirD2 protein.
AB  - Virulence proteins VirD1 and VirD2 are subunits of a relaxosome-like protein
      complex that mediates conjugational transfer of a Ti plasmid segment, the T-DNA,
      from Agrobacterium into higher plants. The VirD1-VirD2 complex binds to 25-bp
      repeats at the borders of the T-DNA and catalyzes sequence-specific nicking of
      the conjugative DNA strand (the T-strand) at the third base of these repeats.
      Nuclear localization signals present in VirD2 target the T-strand to plant cell
      nuclei. In addition, VirD2 probably plays a role in the high-frequency
      integration of the T-DNA into the plant genome by illegitimate recombination.
      Whereas Agrobacterium transformation of dicots is very efficient, T-DNA
      integration in most monocots can barely be detected. To develop an artificial T
      DNA delivery system for monocots, a technique for efficient in vitro production
      of T-strand DNAs was established by using VirD1 and VirD2 proteins purified from
      overexpressing Escherichia coli strains. The topoisomerase-like VirD2 enzyme was
      shown to mediate precise, sequence-specific cleavage of T-DNA border sequences
      carried by single-stranded DNA templates, even in the absence of VirD1 protein.
      During this reaction, VirD2 remains covalently bound to the 5' end of artificial
      T-strand DNAs. In contrast, VirD2, alone or in complex with VirD1, fails to nick
      linear double-stranded DNA templates in vitro.

PMID- 8290584
TI  - Crucial role for DNA supercoiling in Mu transposition: a kinetic study.
AB  - DNA supercoiling plays an indispensable role in an early step of bacteriophage Mu
      transposition. This step involves formation of a nucleoprotein complex in which
      the Mu ends synapse and undergo two concerted single-strand cleavages. We
      describe a kinetic analysis of the role of supercoiling in the Mu-end synapsis
      reaction as measured by the cleavage assay. We observe a dependence of the
      reaction rate on superhelical density as well as on the length of Mu donor
      plasmid DNA. The reaction has a high activation enthalpy (approximately 67
      kcal/mol). These results imply that the free energy of supercoiling is used
      directly to lower the activation barrier of the rate-limiting step of the
      reaction. Only the free energy of supercoiling associated with DNA outside the Mu
      ends appears to be utilized, implying that the Mu ends come together before the
      supercoiling energy is used. Our results suggest an essential function for the
      bacterial sequences attached to the ends of Mu virion DNA.

PMID- 8290585
TI  - Identification of histidine at the catalytic site of the photosynthetic oxygen
      evolving complex.
AB  - The molecular oxygen in our atmosphere is a product of a water-splitting reaction
      that occurs in the oxygen-evolving complex of photosystem II of oxygenic
      photosynthesis. The catalytic core of the oxygen-evolving complex is an ensemble
      of four manganese atoms arranged in a cluster of undetermined structure. The
      pulsed electron paramagnetic resonance (EPR) technique of electron spin-echo
      envelope modulation (ESEEM) can be used to measure nuclear spin transitions of
      nuclei magnetically coupled to paramagnetic metal centers of enzymes. We report
      the results of ESEEM experiments on the cyanobacterium Synechocystis PCC 6803
      selectively labeled with 15N at the two nitrogen sites of the imidazole side
      chain of histidine residues. The experiments demonstrate that histidine is bound
      to manganese in the oxygen-evolving complex.

PMID- 8290587
TI  - Cloning of cDNAs for M-phase phosphoproteins recognized by the MPM2 monoclonal
      antibody and determination of the phosphorylated epitope.
AB  - The MPM2 monoclonal antibody binds to a phospho amino acid-containing epitope
      present on more than 40 proteins of M-phase eukaryotic cells. We have developed a
      technique for cloning cDNAs encoding MPM2-reactive phosphoproteins from
      bacteriophage lambda expression libraries. Proteins from phage plaques were
      absorbed to nitrocellulose filters, phosphorylated by M-phase kinases, and
      screened for MPM2 binding. Partial-length cDNAs encoding two MPM2-reactive
      proteins termed MPM2-reactive phosphoproteins 1 and 2 (MPP1 and MPP2) were
      isolated. The deduced MPP1 and MPP2 amino acid sequences are not closely related
      to any previously described proteins. To determine which amino acid stretches
      contained the MPM2 epitope, sequences from a 15 amino acid peptide expression
      library were selected for binding to MPM2 after phosphorylation by M-phase
      kinases. A string of five amino acids was similar among all selected peptides,
      and the sequence reflecting the most frequent amino acid at each position was Leu
      Thr-Pro-Leu-Lys (LTPLK). MPP1 and MPP2 proteins, respectively, contained five and
      nine sites closely related to LTPLK, including two that were common to both
      proteins, (F/T)TPLQ and SSP(I/S)D. Peptides containing LTPLK and FTPLQ were
      strongly phosphorylated by M-phase, but not interphase, cytosolic kinases, and
      the phosphorylated peptides were bound by MPM2. Thus, we have identified M-phase
      specific phosphorylation sites bound by MPM2 and two putative M-phase
      phosphoproteins containing these sites.

PMID- 8290586
TI  - Function of a human cyclin gene as an oncogene.
AB  - The cyclin D1 (PRAD1, CCND1) gene is affected by translocations and amplification
      in the genomes of a number of human tumors, suggesting that these changes confer
      growth advantage on developing tumor cell clones. We show here that in cultured
      cells, a cDNA clone of the cyclin D1 gene can contribute to cell transformation
      by complementing a defective adenovirus E1A oncogene. In such cells, this
      candidate oncogene indeed functions like an oncogene, suggesting a similar role
      in tumor progression in vivo.

PMID- 8290588
TI  - Nature screen: an efficient method for screening natural populations of
      Drosophila for targeted P-element insertions.
AB  - The efficiency of molecular techniques is making it increasingly necessary to
      rely on reverse genetics to understand the function of genes. Tissue-specific
      libraries allow one to identify numerous genes that can be cloned, sequenced, and
      mapped and whose temporal and tissue-specific pattern of expression are well
      characterized but whose function remains unknown. In such cases, it is desirable
      to generate targeted mutations to examine the phenotype of loss-of-function
      lesions. Here we describe a method for identifying naturally occurring variants
      of Drosophila melanogaster with specific genes tagged by a nearby P element.
      Imprecise P-element excision can then be used to generate a series of small
      deletions in or near the gene. In the method described here, large numbers of
      wild-caught males were crossed to balancer females, and inserts were identified
      in pooled samples by the polymerase chain reaction with one primer from each
      target gene and one primer from the P-element terminal repeat. We present the
      calculations for the probability of successfully tagging a gene and show that it
      is greatly improved by simultaneously screening inserts into several genes. If a
      large natural population is available, a nature screen is faster and easier than
      inducing P-element transposition in the laboratory, but the resulting lines,
      being genetically heterogeneous, may require more subsequent work to isolate.
      Using this method to screen the genomes of approximately 10,400 males, we found P
      element inserts in close proximity to 3 of 10 genes that were screened.

PMID- 8290589
TI  - Allelic associations of two polymorphic microsatellites in intron 40 of the human
      von Willebrand factor gene.
AB  - At intron 40 of the von Willebrand factor (vWF) gene, two GATA-repeat polymorphic
      sites exist that are physically separated by 212 bp. At the first site (vWF1
      locus), seven segregating repeat alleles were observed in a Brazilian Caucasian
      population, and at the second (vWF2 locus) there were eight alleles, detected
      through PCR amplifications of this DNA region. Haplotype analysis of individuals
      revealed 36 different haplotypes in a sample of 338 chromosomes examined. Allele
      frequencies between generations and gender at each locus were not significantly
      different, and the genotype frequencies were consistent with their Hardy-Weinberg
      expectations. Linkage disequilibrium between loci is highly significant with
      positive allele size association; that is, large alleles at the loci tend to
      occur together, and so do the small alleles. Variability at each locus appeared
      to have arisen in a stepwise fashion, suggesting replication slippage as a
      possible mechanism of production of new alleles. However, we observed an
      increased number of haplotypes, in contrast with the predictions of a stepwise
      production of variation in the entire region, suggesting some form of
      "cooperative" changes between loci that could be due to either gene conversion,
      or a common control mechanism of production of new variation at these repeat
      polymorphism sites. The high degree of polymorphism (gene diversity values of 72%
      and 78% at vWF1 and vWF2, respectively, and of 93% at the haplotype level) makes
      these markers informative for paternity testing, genetic counseling, and
      individual-identification purposes.

PMID- 8290590
TI  - Mice lacking N-acetylglucosaminyltransferase I activity die at mid-gestation,
      revealing an essential role for complex or hybrid N-linked carbohydrates.
AB  - Eukaryotic cells require N-linked carbohydrates for survival. However, the
      biosynthetic intermediate Man5GlcNAc2Asn, in place of mature N-linked structures,
      allows glycoprotein synthesis and somatic cell growth to proceed normally. To
      determine whether the same would be true in a complex biological situation, the
      gene Mgat-1 was disrupted by homologous recombination in embryonic stem cells and
      transmitted to the germ line. The Mgat-1 gene encodes N
      acetylglucosaminyltransferase I [GlcNAc-TI; alpha-1,3-mannosyl-glycoprotein beta
      1,2-N-acetylglucosaminyltransferase; UDP-N-acetyl-D-glucosamine:glycoprotein (N
      acetyl-D-glucosamine to alpha-D-mannosyl-1,3-(R1)-beta-D-mannosyl-R2) beta-1,2-N
      acetyl-D-glucosaminyltransferase, EC 2.4.1.101], the transferase that initiates
      synthesis of hybrid and complex N-linked carbohydrates from Man5GlcNAc2Asn. Mice
      lacking GlcNAc-TI activity did not survive to term. Biochemical and morphological
      analyses of embryos from 8.5 to 13.5 days of gestation showed that Mgat-1-/
      embryos are developmentally retarded, most noticeably in neural tissue, and die
      between 9.5 and 10.5 days of development.

PMID- 8290591
TI  - Foot-and-mouth disease virus particles contain replicase protein 3D.
AB  - An antibody against the Escherichia coli-expressed RNA polymerase of foot-and
      mouth disease virus (FMDV) reacts with the virus in ELISA and
      radioimmunoprecipitation experiments and with a protein of the disrupted virus
      particle in an immunoblot analysis. Treatment of the virus with trypsin, which
      cleaves capsid protein VP1 and a 56-kDa polypeptide present in trace amount in
      the particles, reduces the level of the reaction in ELISA and
      radioimmunoprecipitation and eliminates the immunoblot reaction. Electron
      microscopy showed that only approximately 20% of the virus particles reacted with
      the anti-polymerase antibody, whereas most reacted with an antibody against the
      immunodominant G-H loop of the virus. In the presence of ammonium ions, the
      expressed polymerase degrades the RNA of the virus into molecules sedimenting at
      approximately 12 S, indicating that it can act as a hydrolytic as well as a
      polymerizing enzyme. Moreover, the RNA in trypsin-treated virus particles is
      degraded when incubated at 37 degrees C, suggesting that the cleaved 56-kDa
      protein still possesses hydrolytic activity. In addition, the anti-polymerase
      antibody, which inhibits the polymerase activity of the E. coli-expressed
      protein, also partially inhibits the hydrolytic activity of the previously
      described endonuclease of the virus particle, suggesting that this enzyme is
      identical with the polymerase or forms part of it.

PMID- 8290593
TI  - Hyperuricemia and urate nephropathy in urate oxidase-deficient mice.
AB  - Urate oxidase, or uricase (EC 1.7.3.3), is a purine metabolic enzyme that
      catalyzes the conversion of uric acid to allantoin in most mammals except humans
      and certain other primates. The loss of urate oxidase in the human during primate
      evolution predisposes man to hyperuricemia, a metabolic disturbance that can lead
      to gouty arthritis and renal stones. To create a mouse model for hyperuricemia
      and gout, and to address the question of whether urate oxidase is essential in
      lower mammalian species, we have disrupted the urate oxidase gene in the mouse by
      homologous recombination in embryonic stem cells. Unlike the human situation,
      urate oxidase deficiency in mice causes pronounced hyperuricemia and urate
      nephropathy. More than half of the mutant mice died before 4 weeks of age,
      indicating that urate oxidase is essential in mice. These mutant mice may also
      serve as animal models for hyperuricemia and its related nephropathy in humans.

PMID- 8290592
TI  - A rapid capsaicin-activated current in rat trigeminal ganglion neurons.
AB  - A subpopulation of pain fibers are activated by capsaicin, the ingredient in red
      peppers that produces a burning sensation when eaten or placed on skin. Previous
      studies on dorsal root ganglion neurons indicated that capsaicin activates
      sensory nerves via a single slowly activating and inactivating inward current. In
      rat trigeminal neurons, we identified a second capsaicin-activated inward
      current. This current can be distinguished from the slow one in that it rapidly
      activates and inactivates, requires Ca2+ for activation, and is insensitive to
      the potent capsaicin agonist resiniferatoxin. The rapid current, like the slower
      one, is inhibited by ruthenium red and capsazepine. The two capsaicin-activated
      inward currents share many similarities with the two inward currents activated by
      lowering the pH to 6.0. These similarities include kinetics, reversal potentials,
      responses to Ca2+, and inhibition by ruthenium red and capsazepine. These results
      suggest that acidic stimuli may be an endogenous activator of capsaicin-gated
      currents and therefore may rationalize why pain is produced when the plasma
      acidity is increased, as occurs during ischemia and inflammation.

PMID- 8290596
TI  - What would be conserved if "the tape were played twice"?
AB  - We develop an abstract chemistry, implemented in a lambda-calculus-based modeling
      platform, and argue that the following features are generic to this particular
      abstraction of chemistry; hence, they would be expected to reappear if "the tape
      were run twice": (i) hypercycles of self-reproducing objects arise; (ii) if self
      replication is inhibited, self-maintaining organizations arise; and (iii) self
      maintaining organizations, once established, can combine into higher-order self
      maintaining organizations.

PMID- 8290594
TI  - Mouse limb muscle is determined in the absence of the earliest myogenic factor
      myf-5.
AB  - myf-5 is the only member of the MyoD family of myogenic regulatory genes to be
      expressed in the mouse embryo prior to muscle cell differentiation. We have used
      the developing limb as a model in which to follow the formation of peripheral
      muscle, to address the question of whether myogenic precursor cells are already
      present in the limb bud before expression of myf-5. The lacZ reporter gene has
      been introduced into the myf-5 gene by homologous recombination so that its
      expression is under the control of the endogenous myf-5 locus. beta-Galactosidase
      (beta-gal) coloration provides a sensitive assay for myf-5+ cells. Embryos were
      generated from embryonic stem cells carrying this mutation, and the appearance of
      beta-gal+ (myf-5+) cells was followed during limb development in vivo. Limb buds,
      at a stage when they are beta-gal-, were cultured in vitro. After several days,
      beta-gal+ cells accumulated in the premuscle mass. We conclude that determined
      muscle precursor cells in the limb bud do not initially express any member of the
      MyoD family. Furthermore, myogenic precursor cells in the somite, which,
      according to the avian model, migrate from the ventral/lateral edge of the
      dermomyotome to form peripheral muscle masses, are also negative for these
      factors.

PMID- 8290595
TI  - Physical association and functional antagonism between the p65 subunit of
      transcription factor NF-kappa B and the glucocorticoid receptor.
AB  - Glucocorticoids, which are widely used as antiinflammatory agents, downregulate
      the expression of the interleukin 6 gene and of additional cytokine genes
      involved in inflammatory responses. Conversely, the transcription factor NF-kappa
      B, a member of the Rel family of transcription factors, has been implicated in
      the induction of multiple genes involved in the early processes of immune and
      inflammatory responses. This prompted us to investigate whether one of the
      mechanisms by which glucocorticoids exert their antiinflammatory activities is
      through inhibition of gene activation mediated by NF-kappa B. We report that, in
      intact cells, activation of the interleukin 6 promoter by a combination of the
      factor NF-IL6 and the p65 subunit of NF-kappa B is inhibited by dexamethasone
      (ligand)-activated glucocorticoid receptor. Conversely, activation of the mouse
      mammary tumor virus promoter by a combination of dexamethasone and glucocorticoid
      receptor is inhibited by overexpression of p65. Furthermore, we provide evidence
      for physical association between glucocorticoid receptor and p65 in protein
      crosslinking and coimmunoprecipitation experiments, using either in vitro
      translated proteins or those present in cell extracts. These studies suggest that
      direct interactions between NF-kappa B and glucocorticoid receptor may partly
      account for the antiinflammatory properties of glucocorticoids in vivo.

PMID- 8290598
TI  - An integral membrane protein (LMP2) blocks reactivation of Epstein-Barr virus
      from latency following surface immunoglobulin crosslinking.
AB  - The role of latent membrane protein 2 (LMP2) in Epstein-Barr virus (EBV)
      infection was evaluated by using latently infected primary B lymphocytes that had
      been growth transformed by wild-type or specifically mutated EBV recombinants.
      LMP2 null mutant recombinant EBV-infected cells were similar to normal B
      lymphocytes in their rapid increase in intracellular free calcium after surface
      immunoglobulin crosslinking. These cells also became more permissive for lytic
      EBV replication. In sharp contrast, wild-type control infected cells had little
      or no increase in intracellular free calcium or in permissivity for EBV
      replication. The block to surface immunoglobulin crosslinking-induced
      permissivity in cells expressing wild-type LMP2 could be bypassed by raising
      intracellular free calcium levels with an ionophore and by activating protein
      kinase C with phorbol 12-myristate 13-acetate. LMP2A, not LMP2B, mediates this
      effect on calcium mobilization. Genetic and biochemical data are consistent with
      these effects being due to the interaction of the LMP2A N-terminal cytoplasmic
      domain with B lymphocyte src family tyrosine kinases.

PMID- 8290597
TI  - Enhancer 1 binding factor, a Ku-related protein, is a positive regulator of RNA
      polymerase I transcription initiation.
AB  - We have previously characterized a protein, enhancer 1 binding factor (E1BF),
      from rat cells that can modulate RNA polymerase I-directed transcription of the
      rat rRNA gene in vitro. E1BF, a heterodimeric DNA binding protein composed of 72
      kDa and 85-kDa subunits, is related to the human Ku autoantigen with respect to
      immunological and certain structural properties. To establish the direct role of
      E1BF in transcription, we investigated the effect of anti-Ku antibodies on RNA
      polymerase I-directed transcription in rat and mouse cell extracts. These
      antibodies, one directed against the 70-kDa Ku subunit and the other against a
      peptide fragment of this subunit, dissociated the E1BF heterodimer into its two
      subunits. The DNA-protein complex formed in the presence of the antibodies
      contained only the 72-kDa subunit. Preincubation of the extracts with these
      antibodies resulted in an almost complete inhibition of transcription. The
      reduced transcription was observed when either linear or circular template was
      used. The inhibitory effect of the antibodies was greatest when added prior to
      preinitiation complex formation and was minimized significantly when added after
      establishment of the initiation complex. The repression of rRNA gene
      transcription was overcome by the addition of purified E1BF. This study
      demonstrates that E1BF, a Ku-related protein, is required for RNA polymerase I
      directed transcription, the 72-kDa subunit is the major DNA binding polypeptide,
      the factor acts primarily in the formation of the preinitiation complex, and
      heterodimerization of its two subunits is crucial for maintaining the functional
      integrity of the protein.

PMID- 8290599
TI  - Facilitation of glutamate receptors enhances memory.
AB  - A benzamide drug that crosses the blood-brain barrier and facilitates DL-alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated
      synaptic responses was tested for its effects on memory in three behavioral
      tasks. The compound reversibly increased the amplitude and prolonged the duration
      of field excitatory postsynaptic potentials in hippocampal slices and produced
      comparable effects in the dentgate gyrus in situ after intraperitoneal
      injections. Rats injected with the drug 30 min prior to being given a suboptimal
      number of training trials in a two-odor discrimination task were more likely than
      controls to select the correct odor in a retention test carried out 96 hr later.
      Evidence for improved memory was also obtained in a water maze task in which rats
      were given only four trials to find a submerged platform in the presence of
      spatial cues; animals injected with the drug 30 min before the training session
      were significantly faster than vehicle-injected controls in returning to the
      platform location when tested 24 hr after training. Finally, the drug produced
      positive effects in a radial maze test of short-term memory. Well trained rats
      were allowed to retrieve rewards from four arms of an eight-arm maze and then
      tested for reentry errors 8 hr later. The number of such errors was substantially
      reduced on days in which the animals were injected with the drug before initial
      learning. These results indicate that a drug that facilitates glutamatergic
      transmission enhances the encoding of memory across tasks involving different
      sensory cues and performance requirements. This may reflect an action on the
      cellular mechanisms responsible for producing synaptic changes since facilitation
      of AMPA receptors promotes the induction of the long-term potentiation effect.

PMID- 8290600
TI  - Pineal control of aging: effect of melatonin and pineal grafting on aging mice.
AB  - Dark-cycle, night administration of the pineal hormone melatonin in drinking
      water to aging mice (15 months of age) prolongs survival of BALB/c females from
      23.8 to 28.1 months and preserves aspects of their youthful state. Similar
      results were seen in New Zealand Black females beginning at 5 months and C57BL/6
      males beginning at 19 months. As melatonin is produced in circadian fashion from
      the pineal, we grafted pineals from young 3- to 4-month-old donors into the
      thymus of 20-month-old syngeneic C57BL/6 male recipients, and a 12% increase in
      survival was induced. Prolongation of survival was also seen on pineal transplant
      to the thymus in C57BL/6, BALB/cJ, and hybrid female mice at 16, 19, and 22
      months. In all studies, the endogenous pineal of grafted mice was left in situ.
      Pineal grafted aged mice display a remarkable maintenance of thymic structure and
      cellularity. Preservation of T-cell-mediated function, despite age, as measured
      by response to oxazolone is seen. Other evidence suggests that melatonin and/or
      pineal-related factors could produce their effects through an influence on
      thyroid function. These data indicate that pineal influences have a place in the
      physiologic regulation of aging.

PMID- 8290602
TI  - Insulin receptor substrate 1 is required for insulin-mediated mitogenic signal
      transduction.
AB  - Insulin treatment of mammalian cells immediately stimulates the tyrosine
      phosphorylation of a cellular protein of 185 kDa referred to as pp185 or IRS-1
      (insulin receptor substrate 1). The potential role of the IRS-1 protein in
      insulin signaling has been examined by microinjecting affinity-purified
      antibodies into living cells. Stably transfected Rat-1 fibroblasts, which
      overexpress the human insulin receptor, were microinjected and subsequently
      stimulated with insulin or other growth factors. Progression through the cell
      cycle was monitored by using a single-cell assay, which employs bromodeoxyuridine
      labeling of DNA and analysis with immunofluorescence microscopy. Microinjection
      of anti-IRS-1 antibody completely inhibited incorporation of bromodeoxyuridine
      into the nuclei of cells stimulated with insulin or insulin-like growth factor I
      but did not affect cells stimulated with serum or a variety of purified growth
      factors. These studies indicate that IRS-1 is a critical component of the insulin
      and insulin-like growth factor I signaling pathways, which lead to DNA synthesis
      and cell growth.

PMID- 8290601
TI  - Regulation of activity and apical targeting of the Cl-/HCO3- exchanger in rat
      hepatocytes.
AB  - To test the hypothesis that rat hepatocyte canalicular Cl-/HCO3- exchange
      activity might be regulated by HCO3- or protein kinase-induced changes in the
      apical targeting of vesicles, isolated rat hepatocytes were cultured in the
      presence or absence of HCO3-/CO2.Cl-/HCO3- exchange activity increased in cells
      cultured in the presence of HCO3-/CO2 or when stimulated by dibutyryl cAMP. Both
      of these effects were blocked by either colchicine or the protein kinase C
      agonist phorbol 12,13-dibutyrate. Fluorescence and confocal microscopy,
      respectively, revealed increased pericanalicular-apical membrane localization of
      two canalicular markers, peanut agglutinin and a 110-kDa canalicular ecto-ATPase,
      when hepatocyte couplets were preincubated in HCO3-/CO2-containing medium, an
      effect that was again blocked by colchicine. Dibutyryl cAMP also stimulated
      canalicular localization of the 110-kDa protein. These findings suggest that
      hepatocyte Cl-/HCO3- exchange activity is regulated by HCO3-/CO2 and by protein
      kinase A and protein kinase C agonists through microtubule-dependent targeting of
      vesicles containing this exchanger to the canalicular domain.

PMID- 8290603
TI  - Translation elongation factor Tu cleaved by a phage-exclusion system.
AB  - Bacteriophage T4 multiples poorly in Escherichia coli strains carrying the
      defective prophage, e14; the e14 prophage contains the lit gene for late
      inhibitor of T4 in E. coli. The exclusion is caused by the interaction of the e14
      encoded protein, Lit, with a short RNA or polypeptide sequence encoded by gol
      from within the major head protein gene of T4. The interaction between Lit and
      the gol product causes a severe inhibition of all translation and prevents the
      transcription of genes downstream of the gol site in the same transcription unit.
      However, it does not inhibit most transcription, nor does it inhibit replication
      or affect intracellular levels of ATP. Here we show that the interaction of gol
      with Lit causes the cleavage of translation elongation factor Tu (EF-Tu) in a
      region highly conserved from bacteria to humans. The depletion of EF-Tu is at
      least partly responsible for the inhibition of translation and the phage
      exclusion. The only other phage-exclusion system to be understood in any detail
      also attacks a highly conserved cellular component, suggesting that phage
      exclusion systems may yield important reagents for studying cellular processes.

PMID- 8290605
TI  - Predicting Ca(2+)-binding sites in proteins.
AB  - The coordination shell of Ca2+ ions in proteins contains almost exclusively
      oxygen atoms supported by an outer shell of carbon atoms. The bond-strength
      contribution of each ligating oxygen in the inner shell can be evaluated by using
      an empirical expression successfully applied in the analysis of crystals of metal
      oxides. The sum of such contributions closely approximates the valence of the
      bound cation. When a protein is embedded in a very fine grid of points and an
      algorithm is used to calculate the valence of each point representing a potential
      Ca(2+)-binding site, a typical distribution of valence values peaked around 0.4
      is obtained. In 32 documented Ca(2+)-binding proteins, containing a total of 62
      Ca(2+)-binding sites, a very small fraction of points in the distribution has a
      valence close to that of Ca2+. Only 0.06% of the points have a valence > or =
      1.4. These points share the remarkable tendency to cluster around documented Ca2+
      ions. A high enough value of the valence is both necessary (58 out of 62 Ca(2+)
      binding sites have a valence > or = 1.4) and sufficient (87% of the grid points
      with a valence > or = 1.4 are within 1.0 A from a documented Ca2+ ion) to predict
      the location of bound Ca2+ ions. The algorithm can also be used for the analysis
      of other cations and predicts the location of Mg(2+)- and Na(+)-binding sites in
      a number of proteins. The valence is, therefore, a tool of pinpoint accuracy for
      locating cation-binding sites, which can also be exploited in engineering high
      affinity binding sites and characterizing the linkage between structural
      components and functional energetics for molecular recognition of metal ions by
      proteins.

PMID- 8290604
TI  - Eye position and eye velocity integrators reside in separate brainstem nuclei.
AB  - Two types of central nervous system integrators are critical for oculomotor
      performance. The first integrates velocity commands to create position signals
      that hold fixation of the eye. The second stores relative velocity of the head
      and visual surround to stabilize gaze both during and after the occurrence of
      continuous self and world motion. We have used recordings from single neurons to
      establish that the "position" and "velocity" integrators for horizontal eye
      movement occupy adjacent, but nonoverlapping, locations in the goldfish medulla.
      Lidocaine inactivation of each integrator results in the eye movement deficits
      expected if horizontal eye position and velocity signals are processed
      separately. These observations also indicate that each brainstem compartment
      generates and stores these signals. Consequently, each integrator exhibits
      functional autonomy. Therefore, we propose that the intrinsic
      electrophysiological properties of the constituent neurons in each brainstem
      subnucleus may be sufficient for producing integrator rhythmicity.

PMID- 8290606
TI  - Genetic heterogeneity of hepatocellular carcinoma.
AB  - We studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53)
      mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in
      tumors from Mozambique but not in tumors from South Africa, China, and Germany.
      Independent of geographic origin, most tumors were positive for HBV sequences. X
      gene coding sequences of HBV were detected in 78% of tumors, whereas viral
      sequences in the surface antigen- and core antigen-encoding regions were present
      in less than 45% of tumors. These observations indicate that hepatocellular
      carcinomas are genetically heterogeneous. Mozambican-type of hepatocellular
      carcinomas are characterized by a high incidence of p53 mutations related to
      aflatoxins. In other tumors, the rarity of p53 mutations combined with the
      frequent presence of viral X gene coding sequences suggests a possible
      interference of HBV with the wild-type p53 function.

PMID- 8290607
TI  - Weak male-driven molecular evolution in rodents.
AB  - In humans and rodents the male-to-female ratio of mutation rate (alpha m) has
      been suggested to be extremely large, so that the process of nucleotide
      substitution is almost completely male-driven. However, our sequence data from
      the last intron of the X chromosome-linked (Zfx) and Y chromosome-linked (Zfy)
      zinc finger protein genes suggest that alpha m is only approximately 2 in rodents
      with a 95% confidence interval from 1 to 3. Moreover, from published data on
      oogenesis and spermatogenesis we estimate the male-to-female ratio of the number
      of germ cell divisions per generation to be approximately 2 in rodents,
      confirming our estimate of alpha m and suggesting that errors in DNA replication
      are the primary source of mutation. As the estimated alpha m for rodents is only
      one-third of our previous estimate of approximately 6 for higher primates, there
      appear to be generation-time effects--i.e., alpha m decreases with decreasing
      generation time.

PMID- 8290608
TI  - Afferent signals from pigeon extraocular muscles modify the activity of neck
      muscles during the vestibulocollic reflex.
AB  - Movements of the head and eye which, together, result in changes in the direction
      of gaze are linked in a number of species, including man, and eye position is
      known to affect the activity of neck muscles. This head-eye linkage has generally
      been ascribed to modification of neck muscle activity by internal estimates of
      eye position derived from motor commands. We have recently shown that afferent
      signals from stretch receptors in the extraocular muscles are involved in the
      moment-to-moment control of eye movements during the vestibuloocular reflex
      (VOR). We have now studied the interactions between head and eye movements by
      recording the electromyographic activity of several neck muscles during
      horizontal (yaw) or frontal (roll tilt) vestibular stimulation. Such a stimulus
      evokes a VOR in the eyes and a vestibulocollic reflex (VCR) in neck muscles.
      Imposing movements on one eye at saccadic velocities produced considerable
      inhibition of the VCR response of a number of neck muscles. The magnitude of
      these effects was dependent on the parameters of the imposed eye movement. Thus
      systematic changes were seen when the amplitude, velocity or direction of eye
      movement was varied. Movement of the eye in the opposite direction to that
      produced by a normal VOR produced a large inhibition of the VCR response, whereas
      movements in the same direction as the VOR produced only modest inhibition of the
      VCR response of the neck muscles tested. Slow, sinusoidal, imposed eye movements
      that mimicked the slow phase of the VOR produced changes in the gain of the VCR
      response which appear to correct for errors in the imposed eye velocity and thus
      tend to maintain the direction of gaze. The results show that changes in eye
      position have striking effects on the electromyographic activity of neck muscles
      during the VCR, and strongly suggest that extraocular muscle afferent signals are
      involved in head-eye coordination.

PMID- 8290609
TI  - Crosslinking of membrane immunoglobulins and B-cell activation: a simple model
      based on percolation theory.
AB  - In immune network models it is assumed that membrane immunoglobulin (mIg)
      crosslinking leads to B-cell activation. To analyse further the implications of
      this idea, a model of B-cell activation by ligand-induced mIg crosslinking in the
      absence of cell-to-cell interactions is proposed. The present model, based on a
      simple crosslinking mechanism previously proposed by other authors, assumes that
      activation of B-cells is possible once crosslinks of mIgs percolate and that
      percolation of crosslinks can only happen within a relatively short time tau.
      Given a lattice (regular or not), a molecular cluster is said to percolate or to
      become a percolating cluster if it spans the whole lattice (this is the case, for
      instance, of a polymer in a gel phase). From this model of B-cell activation we
      define the activation function fa (LK) as the fraction of B-cells activated after
      tau minutes of interaction with a ligand at concentration L and with affinity K.
      Numerical calculations show that, for current estimates of kinetic constants
      involved in the interaction of a given ligand with a B-cell clone, the activation
      function fa shifts when k-, the dissociation rate constant, is varied below 10(
      3) s-1, this shift being linearly proportional to the variation of k-. This
      result contradicts and, therefore, challenges the assumption in immune network
      models that the activation function is identical for all ligands. This is
      important because the behaviour of at least some of those immune network models
      is quite sensitive to the relative values of the activation function thresholds.

PMID- 8290610
TI  - The evolution of copulatory organs, internal fertilization, placentae and
      viviparity in killifishes (Cyprinodontiformes) inferred from a DNA phylogeny of
      the tyrosine kinase gene X-src.
AB  - Cyprinodontiforms are a diverse group of approximately 900 pantropical and
      temperate fishes, mostly found in freshwater. Whereas the vast majority of fishes
      lay eggs (i.e. are oviparous), this group is unusual in that four groups of
      cyprinodont fishes give birth to living young (i.e. are viviparous). A molecular
      phylogenetic hypothesis was based on partial DNA sequences of the tyrosine kinase
      gene X-src. The study included the major lineages of fishes of the suborder
      Cyprinodontoidei, order Cyprinodontiformes. Our phylogeny agrees with some but
      not all of the conclusions of a previous morphological cladistic analysis
      (Parenti (Bull. Am. Mus. nat. Hist. 168, 335 (1981)). The differences are: (i)
      the Profundulidae are the sister group to the Goodeidae, not the sister group to
      all other cyprinodontoids; (ii) Fundulidae are the sister group to the
      Profundulidae and Goodeidae; (iii) Cubanichthys and the Cyprinodontinae might not
      be sister taxa; (iv) Cubanichthys, and not the Profundulidae, might be the most
      basal member of the cyprinodontoids; and (v) the Anablepinae and Poeciliinae
      might be sister groups. The molecular phylogeny was used to reconstruct the
      evolution of major life-history traits such as internal fertilization, copulatory
      organs, livebearing and placentas. Internal fertilization, modifications of the
      male's anal fin to form a copulatory organ, and viviparity probably evolved
      independently three times in cyprinodontiform fishes: in the subfamilies
      Goodeinae, Anablepinae and Poeciliinae (sensu Parenti 1981). The evolution of
      bundled sperm, spermatozeugmata, is probably not a prerequisite for internal
      fertilization because at least one species with internal fertilization has free
      spermatozoa. Livebearing (viviparity), which takes the form of ovoviviparity
      (where embryos are nourished by their yolk sac only), evolved only in the
      subfamily Poeciliinae. Advanced forms of viviparity, in which the mother provides
      additional nourishment to the embryos through placenta-like structures,
      apparently evolved at least three times from egg-laying ancestors: in the
      subfamilies Goodeinae, Anablepinae, and more than once in the Poeciliinae.

PMID- 8290611
TI  - Relations between song repertoire size and the volume of brain nuclei related to
      song: comparative evolutionary analyses amongst oscine birds.
AB  - Song and brain structure are compared amongst 41 species of oscine birds by using
      the method of independent evolutionary contrasts. We find a significant
      correlation between the relative volume of the song control centre, the high
      vocal centre (HVC), and the number of song types typically found in the
      repertoire. Relative HVC volume is not correlated with the number of different
      syllable types per song bout. The relative volume of a second song nucleus, area
      X, is not significantly correlated with either measure. Relative HVC volume is
      uncorrelated with relative volume of the hippocampus, a brain area involved in
      other forms of memory. This is the first evidence for repeated independent
      evolution of an association between complexity of learned song and the relative
      volume of one of the song control nuclei though to be involved in song learning.

PMID- 8290612
TI  - Titin folding energy and elasticity.
AB  - Molecules of the giant protein titin are responsible for the passive elasticity
      and central A-band location of muscle myofibrils. The molecular mechanism of
      titin elasticity is not known, but the I-band region of the molecule appears
      capable of approximately fourfold reversible extension. Such large extensions are
      likely to involve unfolding of titin domains. In the present experiments,
      equilibrium unfolding of titin from rabbit skeletal muscles was studied in vitro
      by fluorescence and circular dichroism spectroscopy, after addition of
      guanidinium chloride. The data suggest two unfolding transitions, both of which
      appear cooperative. The second transition is likely to involve complete unfolding
      of the immunoglobulin- and fibronectin-like domains from which the molecules is
      composed. The free energy associated with this transition is comparable with the
      energy required to extend titin molecules to the maximum amount seen in situ.

PMID- 8290613
TI  - Frequency-dependent selection, beneficial mutations, and the evolution of sex.
AB  - This paper presents a mathematical model of a population in which multiple
      alleles at a particular locus are maintained by frequency-dependent selection.
      The results suggest that, if the population reproduces sexually, the benefit
      conferred on the population by beneficial mutations at other loci will typically
      be much larger than if the population reproduces by asexual means. In part, this
      is true because, in asexual populations, beneficial mutations can produce
      suboptimal distributions of the alleles that are subject to frequency-dependent
      selection. Another factor that produces an advantage for sex is that, in asexual
      populations, beneficial mutations that have achieved a high copy number may
      nevertheless be lost from the population. This is highly unlikely in sexual
      populations.

PMID- 8290614
TI  - Rhesus monkey copulation calls: honest signals for female choice?
AB  - In a wide variety of mating systems, female choice is based on the assessment of
      male signals, both morphological and behavioural, presumed to correlate with
      fitness. A crucial problem, therefore, is for females to determine whether the
      signal represents an 'honest' reflection of male fitness. A dominant theoretical
      perspective in evolutionary biology suggests that signals are honest if and only
      if they are costly to produce. At present, there are relatively few empirical
      studies of the costs and benefits of signalling in the mating context, and this
      is especially the case for Primates. In this paper, I examine the possibility
      that copulations calls--vocalizations that often elicit aggressive competition
      within the mating arena--are honest signals of male quality. Observations of
      rhesus monkey (Macaca mulatta) mating behaviour reveal that the proportion of
      copulating males who call decreases as competition for oestrous females
      increases. Males who call during copulation are more likely to be aggressively
      attacked than males who are silent during copulation. However, males who give
      copulation calls obtain more matings than males who do not, and this is true for
      high- and low-ranking males. Because of the cost-benefit tradeoffs, copulation
      calls are interpreted as honest indicators of quality that may serve an important
      function in female mate choice.

PMID- 8290615
TI  - Daily and circadian rhythms of synaptic frequency in the first visual neuropile
      of the housefly's (Musca domestica L.) optic lobe.
AB  - Photoreceptors of the fly's compound eye generally show no very obvious daily or
      circadian rhythms, a lack which prompted us to examine whether their function
      might be regulated not in the retina, but at the site of transmission in the
      first visual neuropile, or lamina. Here, photoreceptor terminals (R1-R6) are
      reciprocally interconnected with one class of lamina monopolar cell, L2: L2
      receives input from R1-R6 at so-called tetrad synapses, and in turn is
      presynaptic to R1-R6 at feedback synapses. We have calculated the mean
      frequencies of these synaptic profiles in electron micrographs of single lamina
      sections. L2 feedback synapses were more numerous at night than during the day,
      whereas the number of tetrads showed only small modulations between day and
      night. These changes persisted amongst feedback synapses in flies held in
      constant darkness, and are thus circadian. In contrast to the slow modulations
      during a 24 h cycle, the number of L2 feedback synapses after 1 h light pulse in
      flies held in constant darkness showed no clear change, whereas it increased the
      number of tetrad profiles. These findings support the occurrence of cyclical
      daily and circadian changes amongst the two lamina synaptic populations, with
      tetrads showing rather weak modulations in frequency, but more pronounced
      responses to the light pulse than feedback synapses.

PMID- 8290616
TI  - Physical therapy episodes of care for patients with low back pain.
AB  - BACKGROUND AND PURPOSE: Although individuals with low back pain frequently
      receive treatment from a physical therapist, few published studies exist that
      describe who sees a physical therapist for their low back pain nor is much known
      about physical therapy episodes of care for this condition. Secondary analysis of
      data from the American Physical Therapy Association's Survey of Physical Therapy
      Outpatient Practice provides new descriptive data on services provided to a
      national, representative sample of patients discharged from hospital-based and
      private outpatient practices. In addition, specific hypotheses were tested on
      clinical and background factors believed to influence low back pain episodes of
      care. SUBJECTS: Patients with low back pain represented over 25% of all
      outpatient discharges from physical therapy practices. METHODS: A mail survey was
      conducted with representatives of a national probability sample of facilities
      that provided outpatient physical therapy services. Data were provided on each
      facility and on a discharge sample of patients treated at each facility. RESULTS:
      On average, episodes of care extended over 5 weeks and consisted of 11 therapy
      visits, for an average charge of $766.70. Duration and charge for low back
      episodes of care did not differ, on average, in private versus hospital-based
      practices. Certain aspects of care, however, did vary across regions of the
      country. Episodes of care charged to workers' compensation were costlier than
      those charged to other insurance carriers, and whites were charged less, on
      average, than nonwhites. Duration of back symptoms was related to intensity,
      duration, and charges incurred for the episode of care. CONCLUSION AND
      DISCUSSION: Further research is needed to understand the reasons for the
      relationships observed in this study, as well as studies that relate care
      provided by physical therapists to specific patient outcomes. Further research is
      also needed to compare outcomes achieved across different health professions.

PMID- 8290617
TI  - A prospective study of patients with acute back and neck pain in Sweden.
AB  - BACKGROUND AND PURPOSE: This community-based investigation studied patients with
      acute back/neck pain and prospectively examined risk factors for chronic pain.
      SUBJECTS: One hundred twenty residents (64 men, 56 women) of a rural community in
      Sweden who were off work or had been examined by a physician rural community in
      Sweden who were off work or had been examined by a physician because of acute low
      back/neck pain during a 1-year period were randomly selected to participate in
      the study. METHODS: All subjects were examined by a physical therapist and
      completed questionnaires relating to their functional ability during activities
      of daily living. The subjects were then prospectively followed to examine
      treatment content and possible factors for predicting the development of chronic
      pain. RESULTS: The most common symptom was a dull ache (44%), mostly in the low
      back (56%). In spite of early care, 16 patients who were randomly selected for
      further study developed chronic pain during the follow-up year. The patients with
      chronic pain did not differ from those without chronic pain in age, amount of
      pain, or handicaps. The risk of developing chronic pain, however, was nearly five
      times higher for those patients whose pain was provoked by trunk movements in
      several directions at the first clinical examination. When signs of possible
      nerve root affection were present, the risk for chronic pain development was
      nearly eight times higher. CONCLUSION AND DISCUSSION: These results suggest that
      more attention may need to be paid to patients with these risk factors, so that
      effective preventive measures may be developed.

PMID- 8290618
TI  - Physical therapy management of peripheral vestibular dysfunction: two clinical
      case reports.
AB  - We describe the treatment of two patients with peripheral vestibular dysfunction
      using a novel, staged exercise program. Response to treatment was documented. The
      first patient, a 62-year-old woman with unilateral vestibular dysfunction (UVD)
      and a 6-month history of disequilibrium following herpes zoster oticus resulting
      in damage to the right inner ear, was treated with an 8-week course of vestibular
      physical therapy. During the 8 weeks, the patient attended weekly physical
      therapy sessions and was trained to perform vestibular adaptation exercises on a
      daily basis at home. The second patient, a 53-year-old woman with progressive
      disequilibrium secondary to profound bilateral vestibular hypofunction (BVH), was
      treated with a 16-week course of vestibular physical therapy. During the first 8
      weeks, the patient attended weekly physical therapy sessions and was trained to
      perform vestibular adaptation and substitution exercises on a daily basis at
      home. During the second 8 weeks, the patient continued performing vestibular
      physical therapy exercises at home independently. Vestibular function (sinusoidal
      vertical axis rotation testing), postural control (clinical tests and
      posturography), stability during the performance of selected activities of daily
      living (ADLs), and self-perception of symptoms and handicap were measured prior
      to and at the conclusion of treatment for both patients and at the midpoint of
      treatment for the patient with BVH. After 8 weeks of treatment, both patients
      reported improvements in self-perception of symptoms and handicap and
      demonstrated objective improvements in clinical balance tests, posturography, and
      several kinematic indicators of stability during the performance of selected
      ADLs. Further improvements were noted in the patient with BVH after 16 weeks of
      treatment. Improvements in postural control were noted after 8 weeks of treatment
      for the patient with UVD and after 16 weeks for the patient with BVH. Vestibular
      function improved during the course of treatment for the patient with UVD only.
      These case reports describe two different individualized treatment programs and
      document self-reported and laboratory-measured functional improvements in two
      patients with vestibular deficients--one with unilateral damage and one with
      bilateral damage.

PMID- 8290619
TI  - Gift-giving or influence peddling: can you tell the difference?
AB  - Physical therapists are faced with an ever-increasing array of advertising
      ventures, "free" gifts, and enticing offers from equipment and supply companies
      and various health care agencies. Concerns are raised about the ethical
      implications of gift exchange in professional activities. Basic motives governing
      gift exchange are examined from a sociological standpoint. The obligation of the
      professional to act in the best interest of the patient and to guard against the
      impression of impropriety to the public is paramount in decisions concerning
      gifts. Opinions from the medical and pharmaceutical professions are explored to
      glean criteria that have applicability to physical therapy. These criteria are
      presented in the form of questions that may be helpful for physical therapists.

PMID- 8290620
TI  - Effects of three different posting methods on controlling abnormal subtalar
      pronation.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the effects of
      different orthotic posting methods on controlling abnormal foot pronation during
      ambulation. SUBJECTS: Twenty-two individuals with forefoot varus deformities of
      at least 8 degrees (13 women, aged 21-40 years, and 9 men, aged 20-50 years)
      participated in the study. The female subjects had an average height and weight
      of 162.6 cm (64 in) and 55.3 kg (122 lb), and the male subjects had an average
      height and weight of 175.3 cm (69 in) and 80.7 kg (178 lb). METHODS: The subjects
      were examined with a computerized video motion analysis system. A control trial
      consisted of walking at 4.0 km/h in running shoes. Experimental trials included
      walking at 4.0 km/h in running shoes with unposted orthotic shells and with
      orthotic shells posted in the forefoot, the rear foot, and both forefoot and rear
      foot. RESULTS: Maximal calf-to-calcaneus and calcaneus-to-vertical angles were
      decreased more by orthoses posted in both the forefoot and the rear foot than by
      orthoses posted only in the forefoot. No difference in maximal calf-to-calcaneus
      and calcaneus-to-vertical angles were found with combined forefoot and rear-foot
      posting compared with posting in the rear foot alone. The maximal calf-to
      calcaneus angle was decreased by orthoses posted in any of the three methods and
      by the orthotic shell alone when compared with shoes alone. The maximal calcaneus
      to-vertical angle was decreased by orthoses posted in any of the three methods,
      but not by the orthotic shell alone when compared with shoes alone. CONCLUSION
      AND DISCUSSION: Clinicians should consider combined posting or rear-foot posting
      alone when maximal control of rear-foot frontal-plane pronation is desired,
      though forefoot posting alone and the orthotic shell also provide control of rear
      foot frontal-plane pronation.

PMID- 8290621
TI  - Reliability of passive wrist flexion and extension goniometric measurements: a
      multicenter study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was twofold: (1) to determine
      whether passive wrist flexion and extension goniometric measurements using ulnar
      alignment, radial alignment, and volar/dorsal alignment were similar or
      dissimilar and (2) to examine which of these three techniques had the greatest
      intratester and intertester reliability. SUBJECTS: One hundred forty patients
      (141 wrists) were measured. The testers were 32 therapists from eight different
      hand/upper-extremity clinical sites around the United States. METHODS: Randomly
      paired testers measured passive wrist flexion and extension. The intraclass
      correlation coefficient (ICC) was used as an estimate of agreement for both
      intratherapist (model 3.1) and intertherapist (model 2.1) reliability. RESULTS:
      Six of the eight clinics showed significant differences among the various
      goniometric techniques. Flexion intratherapist mean ICCs for the radial, ulnar,
      and dorsal alignment techniques were .86, .87, and .92, respectively. Extension
      intratherapist mean ICCs were .80, .80, and .84 for the three techniques.
      Intertherapist flexion mean ICCs were .88, .89, and .93 for the radial, ulnar,
      and volar alignment techniques, respectively. Extension intertherapist mean ICCs
      were .80, .80, and .84 for the three techniques. The standard error of
      measurement was also used to quantify reliability, with the volar/dorsal
      alignment technique consistently producing less error than the ulnar and radial
      alignment techniques. The generalizability theory statistical model was utilized
      to identify the sources of error. The patient contributed to variance the most,
      although inherent error within the study, diagnostic category, therapeutic
      approach, and goniometric technique also contributed. CONCLUSION AND DISCUSSION:
      The overall results indicated there were differences among the three goniometric
      techniques. The volar/dorsal alignment technique is the goniometric technique of
      choice, as it consistently had the greatest reliability.

PMID- 8290622
TI  - Factors affecting recruitment of physical therapy personnel in Utah.
AB  - BACKGROUND AND PURPOSE: This study assessed the current and future needs of
      physical therapy personnel in Utah, including both physical therapists and
      physical therapist assistants. SUBJECTS: Three hundred twenty-two health care
      facilities selected from four major employer groups in Utah and a total of 590
      physical therapy personnel were surveyed. Two hundred forty-four health care
      facilities (76%) and 198 physical therapy personnel (33.6%) responded. METHODS:
      Two survey instruments were developed: one to assess the current and future
      supply and demand of physical therapy personnel in Utah, and the other to
      determine recruitment and retention factors. RESULTS: Utah health care facilities
      projected a need for 46 additional physical therapists and 28 additional physical
      therapist assistants in 1992. Surveyed physical therapy personnel reported
      feeling satisfied with the profession and had chosen the profession through a
      person of influence. Freedom on the job and development of skills were the most
      often mentioned determinants of job satisfaction, and pay and benefits were the
      major determinants of retention. CONCLUSION AND DISCUSSION: Physical therapy
      personnel should have a role in recruitment efforts. Physical therapy personnel
      have many options for employment and often choose to seek a diversity of
      opportunities for better compensation.

PMID- 8290623
TI  - Episodes of low back care.

PMID- 8290624
TI  - Regulation of Arabidopsis thaliana L. (Heyn) cor78 in response to low
      temperature.
AB  - Changes in gene expression occur during cold acclimation in a variety of plants
      including Arabidopsis thaliana L. (Heyn). Here we examine the cold-regulated
      expression of A. thaliana cor78. The results of gene-fusion experiments confirm
      the finding of Yamaguchi-Shinozaki and Shinozaki ([1993] Mol Gen Genet 236: 331
      340) that the 5' region of cor78 has cis-acting regulatory elements that can
      impart cold-regulated gene expression. Further, histochemical staining
      experiments indicated that this cold-regulatory element(s) was active at low
      temperature throughout much of the plant including leaves, stems, roots, flower
      petals, filaments, and sepals. Time-course experiments indicated that the
      activity of the cor78 promoter in cold-acclimated plants was down-regulated
      quickly in response to noninducing temperatures and that the half-life of the
      cor78 transcripts was only about 40 min at normal growth temperature. Fusion of
      the entire transcribed region of cor78 to the cauliflower mosaic virus 35S
      promoter resulted in a chimeric gene that was constitutively expressed and
      displayed little if any posttranscriptional regulation in response to low
      temperature.

PMID- 8290625
TI  - Effects of blue and red light on expression of nuclear genes encoding chloroplast
      glyceraldehyde-3-phosphate dehydrogenase of Arabidopsis thaliana.
AB  - We have characterized the effects of different light spectra on expression of the
      nuclear genes (GapA and GapB) encoding chloroplast glyceraldehyde-3-phosphate
      dehydrogenase in Arabidopsis thaliana. Steady-state mRNA levels for both genes in
      etiolated seedlings increased after a short exposure to red or blue light.
      However, these increases could not be reversed by immediate far-red light
      following the initial light treatment. In mature plants, a short light pulse,
      regardless of its spectrum, had no apparent effect on GapA or GapB mRNA levels in
      dark-adapted plants. In contrast, continuous exposure to red, blue, or white
      light resulted in increases of GapA and GapB mRNA levels, with blue and white
      light being far more efficient than red light. Similarly, continuous exposure of
      etiolated seedlings to red, blue, or white light also resulted in increased GapA
      and GapB mRNA levels. In addition, we show that illumination of red light
      saturated Arabidopsis plants with continuous blue light results in further
      increases of GapA and GapB mRNA levels. Based on these results, we conclude that
      both blue light photoreceptor- and phytochrome-mediated pathways are involved in
      light regulation of GapA and GapB genes in Arabidopsis, with blue light acting as
      the dominant regulator.

PMID- 8290626
TI  - Characterization of an Arabidopsis lipoxygenase gene responsive to methyl
      jasmonate and wounding.
AB  - A cDNA corresponding to the gene AtLox2 was isolated from an Arabidopsis thaliana
      library using a lipoxygenase (LOX) probe from soybean. AtLox2 encodes a 102-kD
      protein, AtLOX2, which has 42 to 45% amino acid sequence identity with other
      plant LOX sequences. The AtLOX2 sequence is more than 30 amino acids longer at
      the amino terminus than other plant LOX sequences, and this extension has
      features reminiscent of chloroplast transit peptides, suggesting that AtLOX2 may
      be chloroplast localized. AtLox2 mRNA levels are high in leaves and
      inflorescences but very low in seeds, roots, and stems. AtLox2 mRNA accumulation
      is rapidly induced in leaves in response to methyl jasmonate. Leaves that have
      been wounded and adjacent leaves on the same plant also accumulate AtLox2 mRNA.

PMID- 8290627
TI  - Superoxide dismutase enhances tolerance of freezing stress in transgenic alfalfa
      (Medicago sativa L.).
AB  - Activated oxygen or oxygen free radicals have been implicated in a number of
      physiological disorders in plants including freezing injury. Superoxide dismutase
      (SOD) catalyzes the dismutation of superoxide into O2 and H2O2 and thereby
      reduces the titer of activated oxygen molecules in the cell. To further examine
      the relationship between oxidative and freezing stresses, the expression of SOD
      was modified in transgenic alfalfa (Medicago sativa L.). The Mn-SOD cDNA from
      Nicotiana plumbaginifolia under the control of the cauliflower mosaic virus 35S
      promoter was introduced into alfalfa using Agrobacterium tumefaciens-mediated
      transformation. Two plasmid vectors, pMitSOD and pChlSOD, contained a chimeric Mn
      SOD construct with a transit peptide for targeting to the mitochondria or one for
      targeting to the chloroplast, respectively. The putatively transgenic plants were
      selected for resistance to kanamycin and screened for neomycin phosphotransferase
      activity and the presence of an additional Mn-SOD isozyme. Detailed analysis of a
      set of four selected transformants indicated that some had enhanced SOD activity,
      increased tolerance to the diphenyl ether herbicide, acifluorfen, and increased
      regrowth after freezing stress. The F1 progeny of one line, RA3-ChlSOD-30, were
      analyzed by SOD isozyme activity, by polymerase chain reaction for the Mn-SOD
      gene, and by polymerase chain reaction for the neo gene. RA3-ChlSOD-30 had three
      sites of insertion of pChlSOD, but only one gave a functional Mn-SOD isozyme; the
      other two were apparently partial insertions. The progeny with a functional Mn
      SOD transgene had more rapid regrowth following freezing stress than those
      progeny lacking the functional Mn-SOD transgene, suggesting that Mn-SOD serves a
      protective role by minimizing oxygen free radical production after freezing
      stress.

PMID- 8290628
TI  - Solubilization of functional plasma membrane-localized hepta-beta-glucoside
      elicitor-binding proteins from soybean.
AB  - Total membranes prepared from roots of soybean (Glycine max L.) seedlings have
      previously been shown to contain proteinaceous binding site(s) for a hepta-beta
      glucoside elicitor of phytoalexin accumulation. The hepta-beta-glucoside elicitor
      binding proteins have now been shown to co-migrate with a plasma membrane marker
      enzyme (vanadate-sensitive H(+)-ATPase) on linear sucrose density gradients. With
      the use of detergents, the elicitor-binding proteins have been solubilized in
      functional form from soybean root membranes. The nonionic detergents n
      dodecylsucrose, n-dodecylmaltoside, and Triton X-114, at concentrations of 5 to
      10 mg/mL, each solubilizes between 50 and 60% of the elicitor-binding activity in
      a single extraction of the membranes. A zwitterionic detergent, N-dodecyl-N,N
      dimethyl-3-ammonio-1-propane-sulfonate (ZW 3-12), also solubilizes about 40% of
      the total binding activity at detergent concentrations between 1 and 2 mg/mL, but
      the total binding activity recovered is only approximately 50% of that recovered
      with the nonionic detergents. The elicitor-binding proteins solubilized with
      either n-dodecylsucrose or ZW 3-12 retain the high affinity for radiolabeled
      hepta-beta-glucoside elicitor (apparent dissociation constant [Kd] = 1.8 nM and
      1.4 nM, respectively) that was observed with the membrane-localized binding
      proteins (apparent Kd = 1 nM). Competitive ligand-binding experiments with
      several structurally related synthetic oligoglucosides demonstrate that the
      solubilized binding proteins retain specificity for elicitor-active
      oligosaccharides, irrespective of the detergent used for solubilization.
      Moreover, the binding affinities of the oligoglucosides for the solubilized
      binding proteins correlate well with their abilities to induce phytoalexin
      accumulation in soybean cotyledon tissue. Gel-permeation chromatography of n
      dodecylsucrose-solubilized elicitor-binding proteins demonstrate that the bulk of
      the elicitor-binding activity is associated with large detergent-protein micelles
      (relative molecular weight > 400,000). Our results suggest that n-dodecylsucrose
      is a suitable detergent for solubilizing elicitor-binding proteins from soybean
      root membranes with minimal losses of binding activity. More importantly, we
      demonstrate that solubilization does not significantly after the binding
      properties of the proteins for elicitor-active oligoglucosides.

PMID- 8290629
TI  - Proteolysis of the 85-kilodalton crystalline cysteine proteinase inhibitor from
      potato releases functional cystatin domains.
AB  - The protein crystals found in potato (Solanum tuberosum L.) tuber cells consist
      of a single 85-kD polypeptide. This polypeptide is an inhibitor of papain and
      other cysteine proteinases and is capable of binding several proteinase molecules
      simultaneously (P. Rodis, J.E. Hoff [1984] Plant Physiol 74: 907-911). We have
      characterized this unusual inhibitor in more detail. Titrations of papain
      activity with the potato papain inhibitor showed that there are eight papain
      binding sites per inhibitor molecule. The inhibition constant (Ki) value for
      papain inhibition was 0.1 nM. Treatment of the inhibitor with trypsin resulted in
      fragmentation of the 85-kD polypeptide into a 32-kD polypeptide and five 10-kD
      polypeptides. The 32-kD and 10-kD fragments all retained the ability to potently
      inhibit papain (Ki values against papain were 0.5 and 0.7 nM, respectively) and
      the molar stoichiometries of papain binding were 2 to 3:1 and 1:1, respectively.
      Other nonspecific proteinases such as chymotrypsin, subtilisin Carlsberg,
      thermolysin, and proteinase K also cleaved the 85-kD inhibitor polypeptide into
      functional 22-kD and several 10-kD fragments. The fragments obtained by digestion
      of the potato papain inhibitor with trypsin were purified by reverse-phase high
      performance liquid chromatography, and the N-terminal amino acid sequence was
      obtained for each fragment. Comparison of these sequences showed that the
      fragments shared a high degree of homology but were not identical. The sequences
      were homologous to the N termini of members of the cystatin superfamily of
      cysteine proteinase inhibitors. Therefore, the inhibitor appears to comprise
      eight tandem cystatin domains linked by preteolytically sensitive junctions. We
      have called the inhibitor potato multicystatin (PMC). By immunoblot analysis and
      measurement of papain inhibitory activity, PMC was found at high levels in potato
      leaves (up to 0.6 microgram/g fresh weight tissue), where it accumulated under
      conditions that induce the accumulation of other proteinase inhibitors linked to
      plant defense. PMC may have a similar defensive role, for example in protecting
      the plant from phytophagous insects that utilize cysteine proteinases for dietary
      protein digestion.

PMID- 8290630
TI  - Purification of allantoinase from soybean seeds and production and
      characterization of anti-allantoinase antibodies.
AB  - Allantoinase catalyzes the hydrolysis of allantoin to allantoic acid, a reaction
      important in both biogenesis and degradation of ureides. Ureide production in
      cotyledons of germinating soybean (Glycine max L.) seeds has not been studied
      extensively but may be important in mobilizing nitrogen reserves. Allantoinase
      was purified approximately 2500-fold from a crude extract of soybean seeds by
      differential centrifugation, heat treatment, ammonium sulfate fractionation,
      ethanol fractionation, and fast protein liquid chromatography (Pharmacia) with
      Mono-Q and Superose columns. The purified enzyme had a subunit size of 30 kD.
      Polyclonal antibodies produced against the purified protein titrated allantoinase
      activity in a crude extract of seed proteins. Antibodies recognized the 30-kD
      band in western blot analysis of crude seed extracts, indicating that they were
      specific for allantoinase.

PMID- 8290631
TI  - Barley pathogenesis-related proteins with fungal cell wall lytic activity inhibit
      the growth of yeasts.
AB  - Proteins from intercellular fluid extracts of chemically stressed barley (Hordeum
      vulgare L.) leaves were separated by native polyacrylamide gel electrophoresis at
      alkaline or acid pH. Polyacrylamide gels contained Saccharomyces cerevisiae
      (bakers' yeast) or Schizosaccharomyces pombe (fission yeast) crude cell walls for
      assaying yeast wall lysis. In parallel, gels were overlaid with a suspension of
      yeasts for assaying growth inhibition by pathogenesis-related proteins. The same
      assays were also performed with proteins separated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis under nonreducing conditions. In alkaline
      native polyacrylamide gels, only one band corresponding to yeast cell wall lytic
      activity was found to be inhibitory to bakers' yeast growth, whereas in acidic
      native polyacrylamide gels one band inhibited the growth of both yeasts. Under
      denaturing nonreducing conditions, one band of 19 kD inhibited the growth of both
      fungi. The 19-kD band corresponded to a basic protein after two-dimensional gel
      analysis. The 19-kD protein with yeast cell wall lytic activity and inhibitory to
      both yeasts was found to be different from previously reported barley
      chitosanases that were lytic to fungal spores. It could be different from other
      previously reported lytic antifungal activities related to pathogenesis-related
      proteins.

PMID- 8290632
TI  - 3-Ketoacyl-acyl carrier protein synthase III from spinach (Spinacia oleracea) is
      not similar to other condensing enzymes of fatty acid synthase.
AB  - A cDNA clone encoding spinach (Spinacia oleracea) 3-ketoacyl-acyl carrier protein
      synthase III (KAS III), which catalyzes the initial condensing reaction in fatty
      acid biosynthesis, was isolated. Based on the amino acid sequence of tryptic
      digests of purified spinach KAS III, degenerate polymerase chain reaction (PCR)
      primers were designed and used to amplify a 612-bp fragment from first-strand
      cDNA of spinach leaf RNA. A root cDNA library was probed with the PCR fragment,
      and a 1920-bp clone was isolated. Its deduced amino acid sequence matched the
      sequences of the tryptic digests obtained from the purified KAS III. Northern
      analysis confirmed that it was expressed in both leaf and root. The clone
      contained a 1218-bp open reading frame coding for 405 amino acids. The identity
      of the clone was confirmed by expression in Escherichia coli BL 21 as a
      glutathione S-transferase fusion protein. The deduced amino acid sequence was 48
      and 45% identical with the putative KAS III of Porphyra umbilicalis and KAS III
      of E. coli, respectively. It also had a strong local homology to the plant
      chalcone synthases but had little homology with other KAS isoforms from plants,
      bacteria, or animals.

PMID- 8290633
TI  - Purification, characterization, and complete amino acid sequence of a trypsin
      inhibitor from amaranth (Amaranthus hypochondriacus) seeds.
AB  - A protein proteinase inhibitor was purified from a seed extract of amaranth
      (Amaranthus hypochondriacus) by precipitation with (NH4)2SO4, gel-filtration
      chromatography, ion-exchange chromatography, and reverse-phase high-performance
      liquid chromatography. It is a 69-amino acid protein with a high content of
      valine, arginine, and glutamic acid, but lacking in methionine. The inhibitor has
      a relative molecular weight of 7400 and an isoelectric point of 7.5. It is a
      serine proteinase inhibitor that recognizes chymotrypsin, trypsin, and trypsin
      like proteinase activities extracted from larvae of the insect Prostephanus
      truncatus. This inhibitor belongs to the potato-I inhibitor family, showing the
      closest homology (59.5%) with the Lycopersicum peruvianum trypsin inhibitor, and
      (51%) with the proteinase inhibitor 5 extracted from the seeds of Cucurbita
      maxima. The position of the lysine-aspartic acid residues present in the active
      site of the amaranth inhibitor are found in almost the same relative position as
      in the inhibitor from C. maxima.

PMID- 8290634
TI  - Nucleotide sequence of a cDNA encoding cinnamyl alcohol dehydrogenase from
      Eucalyptus.

PMID- 8290636
TI  - Nucleotide sequence of an Arabidopsis thaliana Lhcb4 gene.

PMID- 8290635
TI  - Sequence of mature phosphoglycerate kinase from spinach chloroplasts.

PMID- 8290637
TI  - Sequence of a cDNA encoding chloroplast fructose-1,6-bisphosphatase from
      rapeseed.

PMID- 8290638
TI  - Nucleotide sequence of a cDNA clone encoding the precursor of ribulose-1,5
      bisphosphate carboxylase/oxygenase small subunit from the fern Pteris vittata.

PMID- 8290640
TI  - Nucleotide sequence of the alpha-amylase gene from Vigna mungo.

PMID- 8290639
TI  - RNA editing of the soybean mitochondrial atp9 transcript.

PMID- 8290641
TI  - A pea cDNA clone (Ihca3) encoding the 24-kilodalton light-harvesting protein of
      photosystem I.

PMID- 8290642
TI  - Isolation and sequencing of tomato fruit sucrose synthase cDNA.

PMID- 8290643
TI  - cDNA encoding tropinone reductase-II from Hyoscyamus niger.

PMID- 8290644
TI  - Nucleotide sequence of a Chlorella vulgaris alpha-tubulin gene.

PMID- 8290645
TI  - Glucose transporter cDNAs from sugarcane.

PMID- 8290646
TI  - Sequence of a cloned tomato ubiquitin conjugating enzyme.

PMID- 8290647
TI  - Nucleotide sequence of a cathepsin D inhibitor protein from tomato.

PMID- 8290648
TI  - Phytoene desaturase from Arabidopsis.

PMID- 8290649
TI  - Cloning and sequencing analysis of a complementary DNA for manganese-superoxide
      dismutase from rice (Oryza sativa L.).

PMID- 8290650
TI  - Isolation and characterization of a cDNA clone encoding a novel short-chain
      alcohol dehydrogenase from Norway spruce (Picea abies L. Karst).

PMID- 8290651
TI  - Sequencing of a soybean alternative oxidase cDNA clone.

PMID- 8290652
TI  - Communication between peritoneal cavity and mediastinal lymph nodes demonstrated
      by Tc-99m albumin nanocolloid intraperitoneal injection.
AB  - Lymphatic drainage from the peritoneal cavity to mediastinal lymph nodes has been
      reported, indicating that abdominal fluid is not immobile. We studied this
      movement in rats receiving Tc-99m albumin nanocolloid which has smaller particle
      sizes than does Tc-99m microaggregated albumin colloid used for liver/spleen
      imaging. The Tc-99m albumin nanocolloid had a radiochemical purity of 99.33%
      99.77% with free pertechnetate of 0.23%-0.67%. During pentobarbital anesthesia,
      thoracoabdominal images were obtained 4-6 hr after intraperitoneal injection of
      350 mCi Tc-99m albumin nanocolloid with 5 ml of normal saline. The images showed
      symmetrical radiotracer localization in the mediastinal lymph nodes.
      Scintigraphic demonstration of drainage to the mediastinal region from the
      peritoneal cavity may be explained by flow directly into mediastinum through the
      lymphatic system, indicating lymphatic patency between the peritoneal cavity and
      mediastinum. Absence of visualization may indicate lymphatic block. This type of
      information concerning lymphatic drainage may have clinical impact for a patient
      with malignant or intractable ascites. The radionuclide technique is easily
      performed for this assessment.

PMID- 8290653
TI  - The induction and characterization of antiserum against human placenta 17-beta
      hydroxysteroid dehydrogenase.
AB  - 17-beta-Hydroxysteroid dehydrogenase was purified from human placenta. The
      purification process included the following steps: 50% saturated ammonium sulfate
      precipitation; heat treatment; affinity column chromatography; and preparative
      SDS gel electrophoretic elution. This enzyme was also characterized by HPLC gel
      filtration and two dimensional gel electrophoresis with isoelectrofocusing. The
      results indicate that the molecular weight of these enzymes in their native
      condition is around 68 kDa and 34 kDa in SDS PAGE. Therefore, the active form of
      the enzyme is an identical dimmer in nature. There are three charged isomers as
      demonstrated by isoelectrofocusing. The antiserum against the 17-beta-HSD was
      induced by injection of purified human placenta 17-beta-HSD in rabbits. The
      antiserum was collected and characterized by ELISA, immunohistochemistry,
      immunoblot and immunoprecipitation tests. The results showed that the antibody
      titer was over 1:12,800, and specificity against human placenta 17-beta-HSD was
      also observed.

PMID- 8290654
TI  - Molecular cloning and relationship of highly repetitive Hind III sequences in
      three cyprinid species: silver carp, bighead carp and grass carp.
AB  - The genomes of three cyprinid species, silver carp, bighead carp and grass carp,
      all contain highly repetitive Hind III sequences. There are two types of repeated
      sequences found in the genome of bighead carp but only one type of repeated
      sequence found in the genomes of silver carp and grass carp. Their lengths are
      from 186 to 201 bp. These sequences are arranged tandemly in the genomes. Their
      copy numbers are about 3.65 x 10(5) per haploid genome and total contents are
      about 5% of the genomes. The Hind III repetitive sequences of silver carp,
      bighead carp and grass carp are very similar to one another but completely
      different from those known repetitive DNAs of common carp, tilapia, pollock and
      salmon.

PMID- 8290655
TI  - Effects of lysine-sensitive aspartokinase III on lysine biosynthesis in
      Escherichia coli K-12.
AB  - A promoterless lysC gene, coding for Escherichia coli aspartokinase III (AKase
      III), has been cloned by phenotypic complementation using plasmid pUC19 as the
      vector. The hybrid plasmid obtained, pUC19AK3, preserved the ribosome binding
      site and transcriptional termination signal of the gene but with a lac promoter.
      E. coli strains containing the recombinant plasmid had high levels of AKase III
      activity. AKase III activity from expressing strains was inhibited by lysine,
      leucine, and S-(2-aminoethyl)-L-cysteine (AEC) but not by threonine and
      methionine. The overexpressed AKase III enzyme had a molecular weight of about 50
      kD from SDS-polyacrylamide gel electrophoresis. N-terminal amino acid sequence
      analysis confirmed that the product from the hybrid plasmid was identical to
      native AKase III rather than a fusion protein. Moreover, overexpression of AKase
      III significantly increased lysine excretion in the plasmid-harboring E. coli
      strain DH1. This increase in the level of AKase III activity also affected other
      metabolites than lysine. Addition of aspartate to the medium brought about
      significant increases in lysine excretion. A maximum increase (about 8-fold) in
      lysine accumulation was observed 45 minutes after incubation in minimal medium
      containing 0.2% aspartate as compared to aspartate-free medium.

PMID- 8290656
TI  - Dominance of the mutant ALDH2(2) allele in the expression of human stomach
      aldehyde dehydrogenase-2 activity.
AB  - About half of Chinese individuals lack mitochondrial aldehyde dehydrogenase-2
      (ALDH2) activity, which is responsible for the oxidation of acetaldehyde produced
      during ethanol metabolism. The ALDH2 deficiency in Chinese has been implicated in
      alcohol flush reaction and reported to be a negative risk factor for development
      of alcohol dependence. To assess the effects of inactive ALDH2 subunits, encoded
      by the mutant ALDH2(2) allele, on the catalytic activity of tetrameric enzyme
      molecules, we have phenotyped ALDH2 from 30 gastroendoscopic biopsies by using
      agarose isoelectric focusing and determined the genotypes from leukocytes of the
      same individuals by using polymerase-chain-reaction amplification and
      hybridization with allele-specific oligonucleotide probes. Sixteen subjects were
      homozygous for the ALDH2(1) allele, one was homozygous for ALDH2(2), and thirteen
      were the heterozygous genotype. None of the subjects with the mutant homozygotic
      and the heterozygotic genotypes exhibited the ALDH2 activity band or intermediate
      bands between ALDH2 and ALDH1 on isoelectric focusing gels. Our results support
      the notion that the mutant allele is dominant and that the heterotetrameric ALDH2
      molecules containing the mutant subunits are enzymatically inactive or far less
      active.

PMID- 8290657
TI  - 32nd Annual Meeting of the New Clinical Drug Evaluation Unit (NCDEU).
      Proceedings. Boca Raton, Florida, May 26-29, 1992.

PMID- 8290658
TI  - Selecting an interim analysis procedure.
AB  - Motivations for undertaking interim analyses differ, as do the methods proposed
      by different authors. This article evaluates five interim analysis procedures
      with regard to different requirements. The five procedures differ with respect to
      concern for the presence or absence of a true treatment effect. One provides
      interim criteria only for accepting Ho (terminating due to insufficient evidence
      of a true treatment effect), two provide criteria only for rejecting H(o), and
      the others provide criteria for either accepting or rejecting H(o). A computer
      program was developed to simulate applications of the interim analyses to
      sampling data. Actual Type I error probabilities, power, probabilities of early
      termination, and expected sample sizes resulting from the different interim
      analysis procedures are compared. One-sided and two-sided tests, equal and
      unequal interim sample segments, and interim alterations in the sample size or
      research design are considered. Results should be helpful in selecting a method
      that satisfies particular interests.

PMID- 8290659
TI  - Central serotonergic changes following antidepressant treatment: a neuroendocrine
      assessment.
AB  - We employed a neuroendocrine challenge paradigm to study the effects of
      antidepressant treatment on serotonergic systems in depressed patients. We
      compared the maximum prolactin response to intravenous clomipramine (CMI) in
      depressed patients who responded to antidepressant treatment to that of
      nonresponders. Pretreatment baseline prolactin concentrations and pretreatment
      prolactin responses to clomipramine challenge were not different in responders
      compared to non-responders. However, following antidepressant treatment, the 6
      responders demonstrated a significant change in their clomipramine challenge test
      results, as indicated by an increase in prolactin responses. In contrast, the 7
      nonresponders did not demonstrate a change in their prolactin response to
      clomipramine challenge following treatment. These data support the hypothesis
      that serotonergic system dysfunction, as manifested by blunted prolactin response
      to clomipramine challenge, tends to normalize after successful treatment for
      depression, and that abnormal serotonergic function may be a state-dependent
      characteristic.

PMID- 8290660
TI  - Effect size as a measure of symptom-specific drug change in clinical trials.
AB  - A data-analytic strategy is proposed for identifying the symptom-specific effects
      of each medication in a clinical trial. The within-group effect size is a
      standardized ratio of the pre-post change relative to the stability of change for
      each treatment group. Advantages of using this descriptive approach are
      illustrated by examining antidepressant effects of alprazolam, imipramine, and
      placebo in a clinical trial for patients meeting criteria for both panic disorder
      and depression. There was a significant difference between active medication and
      placebo on the Hamilton Rating Scale for Depression (HAM-D) total, but no
      difference between the anti-depressant effects of the active medications despite
      their diverse psychopharmacologic properties. Examination of effect sizes for
      each HAM-D item revealed distinct symptom-specific effects of each active
      medication in this study sample. Although these descriptive findings cannot be
      used for inferential conclusions, they can be used to guide the design of future
      trials.

PMID- 8290661
TI  - Efficacy and safety of b.i.d. doses of venlafaxine in a dose-response study.
AB  - In this study, 312 depressed outpatients received either placebo or one of three
      venlafaxine doses twice daily (b.i.d.) for up to 6 weeks. The total daily doses
      of venlafaxine were 25, 50-75, and 150-200 mg/day. Hamilton Rating Scale for
      Depression (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS) total
      scores at Week 6 were significantly lower for the high-dose group than for the
      placebo group. A positive dose-response trend for the primary efficacy parameters
      was demonstrated as early as Week 1. Venlafaxine was well tolerated at all dose
      levels. The most common side effects of clinical interest were nausea and dry
      mouth. The frequency of nausea in the venlafaxine groups was essentially the same
      (25-29%), whereas the frequencies of dry mouth, somnolence, and sweating were
      dose related. The results indicate that b.i.d. doses of venlafaxine are safe and
      effective in treating depression.

PMID- 8290662
TI  - A quantitative analysis of clinical drug trials for the treatment of affective
      disorders.
AB  - This article presents a metaanalysis of approximately 300 studies of drug
      treatment for affective disorders. Efficacy is proven beyond a shadow of a doubt
      in this overview from random-assignment, double-blind studies. The efficacy of
      maintenance antidepressants is supported by a large body of evidence. The size
      effect of drug versus placebo difference used to prevent recurrence of unipolar
      or bipolar affective disease is comparable to the size effect of drug versus
      placebo difference for the treatment of an acute episode.

PMID- 8290663
TI  - Preliminary report: placebo-controlled, double-blind study of the clinical and
      metabolic effects of desipramine in panic disorder.
AB  - Fifty-six males and females with panic disorder with or without agoraphobia
      participated in a 12-week, placebo-controlled treatment study of the efficacy of
      desipramine (DMI). Twenty-six of 28 patients receiving DMI completed the study;
      17 of 28 placebo (PBO) recipients completed 12 weeks. Patients receiving DMI
      responded significantly better than did PBO recipients as measured by Hamilton
      Anxiety Scale (HAM-A) and global phobia ratings, with a trend toward greater
      global improvement, but no between-group differences on panic attack frequency
      were discerned. By Week 12, 22 of 26 (85%) DMI patients were panic-free; 13 of 17
      (76%) PBO patients were panic-free. Resting metabolic rate (RMR) was tested on a
      subset of the patients. Patients receiving DMI showed no effects on RMR or
      thyroid indices but lost a significant amount of weight; the PBO recipients
      exhibited no weight loss or RMR effects. In this study, the high PBO response
      rate obscured treatment group differences on some measures. This study
      underscores the need for placebo comparisons in treatment studies. In summary,
      DMI appears to be an effective treatment for panic disorder. DMI appears to have
      little effect on RMR; a slight but significant weight loss was observed in the
      DMI but not PBO group.

PMID- 8290664
TI  - A three-generational presentation of separation anxiety in childhood with
      agoraphobia in adulthood.
AB  - School phobia belongs to a family of childhood anxiety states that appear to be
      related to adult forms of anxiety disorders, particularly to panic disorder with
      agoraphobia. School phobia appears to affect at least 5 percent of elementary
      school children and 2 percent of middle school children. Many of these children
      would be classified under the current DSM-III-R system of nomenclature as
      suffering from separation anxiety disorder. The present study is related to the
      elaboration of a three-generation family presentation of separation anxiety
      disorder manifesting itself as school phobia in childhood, which evolves toward
      panic disorder with agoraphobia in young adulthood and diffuse anxiety with
      hypochondriacal features in later life. All 13 genetically related members of the
      family investigated have been afflicted. The children with separation anxiety
      disorder and school phobia in this family who have been treated with imipramine
      have shown a resolution of anxiety symptoms that has allowed their successful
      return to school. The information from this family would fit into a model that
      describes a spectrum of anxiety disorders that present with different
      manifestations of overt psychopathology throughout the life cycle. We hope to
      follow this family prospectively over the next 30 years.

PMID- 8290665
TI  - Fluoxetine trial in suicidal depressed alcoholics.
AB  - The selective serotonergic agonist fluoxetine has demonstrated efficacy in the
      treatment of depression and has suggested efficacy in the treatment of
      alcoholism. However, no trials with any selective serotonin agonist have been
      reported in patients who display both major depression and alcoholism. In this
      study, 12 patients with DSM-III-R diagnoses of major depressive disorder and
      alcohol dependence were treated openly with fluoxetine for 8 weeks, with doses
      ranging from 20 mg to 40 mg p.o. qAM. All 12 patients reported prominent suicidal
      ideation upon admission to our hospital; 6 had made serious suicide attempts
      shortly before admission. Statistically significant improvements were noted on
      measures of depression and postdischarge alcohol consumption. No paradoxical
      increases in suicidality were noted. These findings suggest that fluoxetine has
      potential for treating the depressive symptoms and the excessive alcohol intake
      of depressed alcoholics.

PMID- 8290666
TI  - Increases in heart rate variability with successful treatment in patients with
      major depressive disorder.
AB  - We obtained Hamilton Rating Scale for Depression (HAM-D) scores and recorded 5
      minutes of rhythm strip both before and after a therapeutic trial of
      antidepressant medications in 17 patients diagnosed with major depressive
      disorder (MDD). We calculated the standard deviation (SD) of interbeat intervals
      and the mean squared successive difference (MSSD) as measures of heart-rate
      variability (HRV). We then calculated Spearman rank-ordered correlation
      coefficients between the HRV measures and the HAM-D scores. Changes in SD and
      MSSD correlated with post-treatment HAM-D scores and with changes in HAM-D
      scores. These relationships were strongest in patients who responded positively
      to nontricyclic antidepressant medications. HRV before treatment was not
      predictive of treatment response, nor did HRV reliably reflect the severity of
      depressive symptoms. These findings indicate that pharmacologic treatment leading
      to improvement in MDD is associated with increased HRV. Hence, brief measures of
      HRV could be developed as a useful adjunctive, physiologic measure of treatment
      response to pharmacotherapy in clinical trials and other settings. Further,
      increased HRV associated with successful treatment of MDD may reflect improved
      autonomic function, decreasing the risk of cardiovascular mortality found in
      patients with MDD.

PMID- 8290667
TI  - Pergolide: an antidepressant adjuvant for mood disorders?
AB  - Pergolide, a dopamine (DA) agonist, can be a useful adjunct to antidepressant
      pharmacotherapy, both with tricyclic antidepressants and with monoamine oxidase
      inhibitors (MAOIs). Pergolide improved or very much improved (as measured by the
      Clinical Global Impressions Global Improvement Scale) 11 of 20 previously
      refractory unipolar and bipolar patients. Patients typically described an
      improvement in their mood, interest, and energy within a week. The range of
      effective dosage is from 0.25 mg to 2 mg, typically 0.5 mg to 1 mg. Pergolide
      does not work alone. There must be a concomitant antidepressant, either MAOI or
      non-MAOI type. Nausea and vomiting are sometimes treatment-limiting side effects.
      Hypomania is a risk but is quickly and permanently reversible by lowering the
      pergolide dose. The treatment implication for the future is that potent DA
      agonists such as pergolide may have a role as antidepressant adjuvants. This
      possibility is in contrast to the negative impressions of weaker DA agonists used
      alone.

PMID- 8290668
TI  - Divalproex sodium treatment in late adolescent and young adult acute mania.
AB  - This is a preliminary report on 6 subjects in an ongoing open trial of divalproex
      sodium in the treatment of adolescents with bipolar affective disorder who are
      experiencing an acute manic episode. The 7-week study was designed to determine
      the relative potential efficacy and safety of divalproex sodium in this condition
      before further assessment of the medication with a comparative lithium condition.
      Patients were assessed weekly with the Modified Mania Rating Scale (MMRS), the
      Brief Psychiatric Rating Scale (BPRS), and the Global Assessment Scale (GAS). The
      primary outcome measure was the MMRS. Of the 6 patients, 5 showed marked
      improvement (pre-post decrease > 60%), 1 showed some improvement (pre-post
      decrease of 20-60%), and none failed to improve (pre-post decrease of < 20%). The
      mean MMRS score was significantly reduced by 7 weeks of treatment (pre to post
      mean score: 77 +/- 25.79 to 29 +/- 24.97, t = 9.45, p < .0002), as were the BPRS
      (40.67 +/- 14.91 to 18.67 +/- 11.83, t = 5.98, p < .0019) and the GAS (28.5 +/-
      12.78 to 48 +/- 15.03, t = 6.71, p < .0011). All patients were on ancillary
      psychotropic medications during this study.

PMID- 8290669
TI  - Plasma beta-endorphin levels, naltrexone, and haloperidol in autistic children.
AB  - Plasma beta-endorphin levels were measured in 13 autistic children, aged 3.67 to
      11.67 years at the end of treatment (naltrexone, haloperidol, pimozide, or
      placebo) and in 5 of the 13 children also at baseline. Baseline plasma beta
      endorphin levels were lower than those reported in the literature. There was a
      strong correlation between plasma beta-endorphin levels and severity of
      sterotypies in all children. Naltrexone did not seem to have a specific effect on
      plasma beta-endorphin levels; short-term haloperidol treatment was associated
      with an increase, whereas long-term haloperidol treatment seemed to have a
      depressive effect on plasma beta-endorphin levels, which rose after withdrawal of
      haloperidol.

PMID- 8290670
TI  - Mismatch negativity in hyperactive children: effects of methylphenidate.
AB  - This pilot study investigates electrophysiological correlates of methylphenidate
      (MP) treatment among hyperkinetic children who are clinical responders to
      therapy. Event-related potentials were obtained from a small sample (6
      hyperactive and 5 controls) during an auditory "oddball" task. In the ignore
      condition, oddball tones elicited a frontocentral "mismatch" negativity (MMN)
      during the 100- to 200-msec latency range following stimulus presentation. In the
      attend condition, oddball target tones elicited a centroparietal P3 as well. MP
      significantly decreased hyperkinetic behaviors. Preliminary analyses of the
      electrophysiological data indicated a decreased amplitude of the P3 waveform
      among hyperkinetic children and a trend toward normalization on MP. Waveform
      abnormalities in the latency range of control MMN suggested either a decrease in
      MMN amplitude or an increase in MMN latency in hyperactive subjects along with a
      trend toward normalization by MP. The preliminary data are suggestive of
      information-processing abnormalities among hyperactive children that may be
      sensitive to MP therapy.

PMID- 8290672
TI  - Psychotherapeutic Medications Development Program (PMDP).
AB  - The Psychotherapeutic Medications Development Program (PMDP) of the National
      Institute of Mental Health was established in 1990. The purpose of the PMDP is to
      improve, enhance, and speed the development of new medications and improve the
      therapeutic usefulness of existing medications for the treatment of mental
      illness. The PMDP will fulfill this mission by implementing four initiatives. In
      the drug discovery and development initiative, the PMDP will aid in the
      development of promising new drugs. This initiative will also include improving
      the therapeutic usefulness of existing medications. In the technology transfer
      initiative, PMDP will improve the technology transfer from academic and
      government researchers to the pharmaceutical industry; improve the dissemination
      of information concerning technology transfer opportunities as it pertains to
      psychotherapeutic medications; and enhance technology transfer by acting as a
      broker to bring interested parties together. For the third initiative, the PMDP
      will develop and maintain a capability to clinically evaluate psychotherapeutic
      medications. The PMDP will also act to facilitate the development and testing of
      new concepts and models of mental illness. There is a detailed description of the
      steps that are involved in developing a new chemical entity (NCE) from the
      conceptual stage to a medication that is approved for the treatment of a
      particular illness. The pharmaceutical industry estimates that this medication
      development process costs $238 million.

PMID- 8290671
TI  - Pharmacologic relationship of antisaccade and dyskinesia in schizophrenic
      patients.
AB  - Abnormalities in saccadic eye movements have been found in schizophrenics with
      tardive dyskinesia (TD). This finding supports accumulating evidence for a
      GABAergic dysfunction in the subcortical-cortical circuits controlling motor and
      oculomotor behavior. We found that in response to muscimol, a direct-acting GABA
      agonist, changes in the antisaccade error rate and dyskinesia score were strongly
      correlated. We then looked at the relationship between these measures during
      single-blind haloperidol withdrawal. Significant changes occurred in antisaccade
      error during drug withdrawal, but the final measure was not significantly
      different from the baseline assessment. Antisaccade error change scores were not
      correlated with dyskinesia change scores. Change score in antisaccade error was
      positively correlated with change on the Brief Psychiatric Rating Scale,
      specifically with the Anxiety/Depression factor. These findings suggest that
      GABAergic mechanisms are more robust than dopaminergic mechanisms in the
      pathophysiology of persistent tardive dyskinesia.

PMID- 8290673
TI  - Thioridazine improves affective symptoms in schizophrenic patients.
AB  - Consenting schizophrenic patients ranging in age from 18 to 63 years were
      withdrawn from antipsychotics for at least 1 week and randomly assigned to
      receive identical capsules of thioridazine (n = 13), molindone (n = 10), or
      haloperidol (n = 12) for a minimum of 6 weeks. Compared with the molindone- and
      haloperidol-treated patients, the thioridazine-treated patients were
      significantly improved over time as measured by Brief Psychiatric Rating Scale
      (BPRS) and Hamilton Rating Scale for Depression (HAM-D) total scores. Improvement
      in BPRS scores was due largely to improvement in symptoms of anxiety and
      depression. Subjects did not differ significantly on other measures, with the
      important exception of weight. On average, molindone patients lost 5 pounds over
      the 6 weeks of treatment, whereas thioridazine patients gained 6 pounds.
      Haloperidol-treated patients had no significant weight changes.

PMID- 8290674
TI  - High plasma clozapine levels in tardive dyskinesia.
AB  - Studies in the literature that attempt to relate neuroleptic plasma levels to the
      development of tardive dyskinesia (TD) report inconsistent findings. As part of
      an open, long-term study, 60 schizophrenic and schizoaffective patients were
      started gradually on a b.i.d. schedule of the atypical antipsychotic drug
      clozapine. Blood samples were drawn weekly for 6 weeks and analyzed for a variety
      of constituents including clozapine plasma levels. Patients with higher levels of
      TD were found to have significantly higher levels of plasma clozapine and a
      higher ratio of plasma/dose than those with lower levels of TD. Our data suggests
      that schizophrenics with TD may have different pharmacokinetics, drug metabolism,
      and elimination processes than those without TD. Higher typical plasma
      neuroleptic levels may increase susceptibility to TD development. A second
      hypothesis implies that it is not the higher mean plasma level of a neuroleptic
      that is associated with TD but the greater fluctuations of plasma levels over
      time (i.e., a higher variance). This hypothesis is discussed in the context of
      our data.

PMID- 8290675
TI  - Factor stationarity and invariance of the POMS in cocaine patients.
AB  - The Profile of Mood States (POMS) factor scores are commonly used to evaluate the
      clinical pharmacologic effects of a drug. Two assumptions made when using the
      POMS in this manner are that its factor structure remains constant across time
      (factor stationarity) and that the factor structure is identical across
      experimental groups (factor invariance). If these assumptions are not met, then
      interpreting change in POMS factor scores becomes problematic. Structural
      equation modeling programs (e.g., LISREL) may be used to explicity test
      assumptions of factor stationarity and invariance. As part of a National
      Institute on Drug Abuse grant-funded, double-blind, placebo-controlled trial to
      assess effectiveness of treating cocaine-abusing patients with fluoxetine, POMS
      data were collected at baseline and at 6 weeks (n = 90). Applying a longitudinal
      factor analysis strategy, factor stationarity and invariance of two POMS factors
      were assessed in this patient sample.

PMID- 8290676
TI  - Stabilization and depot neuroleptic dosages.
AB  - Little is known about the stabilization phase of schizophrenia. To address this
      deficiency, we studied the prescribing patterns of fluphenazine decanoate (FZD)
      for a cohort of schizophrenic patients recovering from an acute psychotic episode
      who were being followed in the Treatment Strategies in Schizophrenia (TSS) multi
      site maintenance study. Dosage data from the first 208 successfully-stabilized
      TSS subjects were examined. We hypothesized five groups on the basis of dosage
      prescribed and dosage stability over time: (1) STABLE HIGH, (2) STABLE
      INTERMEDIATE, (3) STABLE LOW, (4) UNSTABLE RAISING, and (5) UNSTABLE LOWERING.
      The dosage patterns were rated and analyzed against predictive and outcome
      variables. Most of the subjects (n = 168, or 82%) fit one of the five
      hypothesized dosage pattern groups. Our preliminary findings are as follows: (1)
      all groups improved during stabilization; (2) baseline symptom severity did not
      distinguish among dosage pattern groups; (3) STABLE dose groups needed less time
      to stabilize than did the UNSTABLE groups, but the STABLE groups did not have a
      better medication response; (4) many of the UNSTABLE LOWERING subjects apparently
      received a "loading dose" strategy (e.g., initial FZD dose > or = 25 mg), which
      was paradoxically associated with a longer stabilization time.

PMID- 8290677
TI  - Plasma gamma-aminobutyric acid (GABA) is low in alcoholics.
AB  - Plasma levels of gamma-aminobutyric acid (GABA) were measured in male alcoholics
      on admission to inpatient treatment and at discharge after 3 to 4 weeks of
      abstinence. Free plasma GABA at discharge was significantly lower in alcoholics
      than in control subjects and specifically identified a subset of 35 percent of
      the alcoholic patients with levels below the normal range. However, levels of
      free plasma GABA in recently detoxified alcoholics on admission were not
      different from those of controls and had a significant positive correlation with
      liver enzymes and mean corpuscular volume. These data are compatible with a GABA
      deficit theory of alcoholism in a subset of alcoholics.

PMID- 8290678
TI  - A controlled comparison of the effects of propranolol, benztropine, and placebo
      on akathisia: an interim analysis.
AB  - A group of 28 patients was treated to compare the effects on akathisia of the
      following: propranolol (80 mg/day), benztropine (6 mg/day), or placebo. Both
      propranolol and benztropine significantly improved akathisia by Day 3-5 of
      treatment. Placebo had no significant effects of akathisia. Three patients
      developed confusion or forgetfulness by Day 3 of benztropine treatment; these
      effects cleared upon discontinuation of benztropine.

PMID- 8290679
TI  - Haloperidol withdrawal and weight changes in autistic children.
AB  - The long-term effects of haloperidol on weight were assessed in 30 children, 25
      males and 5 females, diagnosed with autistic disorder whose ages ranged from 3.08
      to 8.42 years. They received haloperidol (0.25-3.50 mg/day; mean 1.26 +/- 0.84)
      for 6 months followed by a 4-week drug withdrawal period. Weights obtained on the
      last day of the 6-month haloperidol period were compared to weights obtained
      following drug withdrawal. There was no significant difference between the mean
      weights obtained on the last day of haloperidol administration (24.799 +/- 9.741
      kg) compared to the mean weights at the end of the fourth week of the placebo
      period (24.644 +/- 9.833 kg). Weights increased during the first week of drug
      discontinuation (24.879 +/- 9.855 kg), but decreased during each following week
      of drug withdrawal. Weight was measured monthly during the 6-month haloperidol
      treatment period for 8 of the 30 subjects. In this subsample, weight gain was
      greater during the 1-month period lasting from the end of the 4-week drug
      withdrawal to the end of the first month after resuming haloperidol treatment
      than weight gain prior to drug withdrawal, between the fifth and sixth month of
      haloperidol treatment.

PMID- 8290680
TI  - Psychobiological correlates of poor response to cognitive behavior therapy:
      potential indications for antidepressant pharmacotherapy.
AB  - Correlates of outcome were studied in a sample of 142 unmedicated patients with
      major depressive disorder treated with cognitive behavior therapy (CBT) in
      outpatient (n = 110) or inpatient (n = 32) protocols. Outpatients received up to
      20 sessions of therapy over 16 weeks; inpatients received up to 20 sessions over
      4 weeks. Across all three protocols, nonresponse was associated with
      unemployment, higher levels of pretreatment severity, and an abnormal
      electroencephalographic (EEG) sleep profile. Chronicity was associated with poor
      outcomes in male outpatients, whereas high scores on a measure of dysfunctional
      attitudes were associated with a trend for poor outcome only in female patients.
      Among inpatients, male gender, diagnostic comorbidity, and elevated urinary free
      cortisol levels also were associated with poor outcome. Although a majority of
      the unmedicated patients experienced full or partial remissions, our findings
      suggest that assessments of both clinical (e.g., severity, chronicity, and
      comorbidity) and psychobiological (EEG sleep and adrenocortical function) factors
      may identify those depressed patients who are less likely to benefit from CBT
      alone. Such patients may be preferentially responsive to treatment with
      pharmacotherapy, either alone or, in more complicated cases, in combination with
      psychotherapy.

PMID- 8290681
TI  - Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure.
AB  - The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is a self
      report measure designed to enable investigators to easily obtain sensitive
      measures of the degree of enjoyment and satisfaction experienced by subjects in
      various areas of daily functioning. The summary scores were found to be reliable
      and valid measures of these dimensions in a group of depressed outpatients. The Q
      LES-Q measures were related to, but not redundant with, measures of overall
      severity of illness or severity of depression within this sample. These findings
      suggest that the Q-LES-Q measures may be sensitive to important differences among
      depressed patients that are not detected by the measures usually employed.

PMID- 8290682
TI  - Nortriptyline in the hospitalized elderly: tolerance and side effect reduction.
AB  - This article describes two separate but related studies regarding the use of
      nortriptyline (NT) in the treatment of depressed elderly inpatients. The first
      study assesses medication tolerance to NT during the acute treatment of late-life
      depression. The second describes a placebo-controlled study of the effect of
      bethanechol in reducing antimuscarinic side effects of NT. Antidepressant
      pharmacotherapy was considered for 72 patients with late-life depression; 17
      (24%) did not receive NT; 5 (7%) because of absolute or relative medical
      contraindications. Of the 55 patients who started on NT, 9 percent had side
      effects that necessitated medication discontinuation. A separate sample of 26
      elderly depressed patients being treated with NT participated in a double-blind,
      placebo-controlled trial of bethanechol. Patients receiving bethanechol had
      reduced subjective complaints of anticholinergic side effects and showed
      improvement on an objective measure of salivary flow.

PMID- 8290683
TI  - Haloperidol vs. phenelzine in continuation therapy of borderline disorder.
AB  - We report the first double-blind, placebo-controlled continuation study
      comparison of a neuroleptic (haloperidol < or = 6 mg), monoamine oxidase
      inhibitor (MAOI) antidepressant (phenelzine < or = 90 mg), and placebo in 54
      patients with borderline personality disorder. Continuation medication trials of
      16 weeks followed 5 weeks of acute therapy. Haloperidol continued to be effective
      beyond the acute phase only for the treatment of irritability. Higher levels of
      depression, hypersomnia, and leaden paralysis were noted in the haloperidol group
      than in the phenelzine and placebo groups. The dropout rate during the first half
      (8 weeks) of the continuation study was significantly higher for the haloperidol
      group (64%) than for the placebo group (28%) (p < .05). Phenelzine demonstrated
      very modest efficacy beyond that noted in the acute phase for the treatment of
      depression and irritability. Phenelzine was shown to have an activating effect on
      measures of excitement and reactivity.

PMID- 8290684
TI  - Public health versus personal health.

PMID- 8290685
TI  - Criteria for decision making in local research (ethics) committees.
AB  - This paper briefly reviews the role in medical ethics of the British Medical
      Association and the General Medical Council. It describes the origin of local
      research ethics committees and then outlines the criteria which should be used in
      such committees to assess the ethics of research protocols, based on current best
      practice in the United Kingdom.

PMID- 8290686
TI  - Child protection in schools: a survey of the training needs of Fife
      schoolteachers.
AB  - Teachers have an important role to play in child protection. This lies not only
      in the detection and reporting of possible cases of child abuse but also in multi
      disciplinary teamwork, and in contributing to the ongoing support and monitoring
      of the abused child. Their role can only be properly carried out if teachers are
      equipped with the relevant skills. Appropriate in-service training in child
      protection for teachers is of key importance in both emphasising child protection
      issues and in promoting these skills in teachers. In order to guide the
      development of a training course for teachers in child protection, a survey of
      Fife teachers was carried out to investigate the knowledge, attitudes and
      practices of teachers with respect to a range of child protection issues. This
      confirmed that teachers consider child protection to be an important subject of
      direct relevance to their work as teachers. In-service training on this issue was
      almost unanimously welcomed. The study showed that although the knowledge of
      teachers regarding the signs of child abuse was reasonably good, in practice 40%
      of teachers did not feel confident in handling these issues. This has important
      implications for the design of training courses. Very few schools had established
      school child protection policies although the majority of teachers stated that
      such policies would be useful.

PMID- 8290687
TI  - An observational study of car occupant restraint in Fife: impact of recent
      legislation.
AB  - During August 1992 an observational study of car occupant restraint use was
      carried out at 14 sites throughout Fife (representing traffic-signal-controlled
      junctions in rural and non-rural sites and observations made outside primary
      schools). This study replicated another completed in April 1991 before the most
      recent legislation on rear seat restraints. The overall restraint use found at
      the traffic signal sites (excluding taxis) was 87% (drivers 94%, front seat
      passengers 93% and rear seat passengers 59%). There was lower restraint use (68%)
      in cars taking children to and from primary schools (drivers 87%, front seat
      passengers 77% and rear seat passengers 50%). Passengers seated in rear centre
      seats were least likely to be restrained (40%) especially where they were an
      older child or adult (only 14% of this latter group being restrained). Restraint
      use in taxi cabs was low (drivers 11%, passengers 41%). Since rear seat
      legislation was introduced in July 1991 there has been a 77% increase in rear
      seat restraint use, especially in older children and adults (233% increase) and
      in 1-4-year-old children (119% increase); it is likely that these improvements
      are largely as a result of the legislation. However, approximately 40% of rear
      seat passengers still travel without rear seat belt restraint. There is therefore
      a continuing need to emphasise both public education and the enforcement of
      current legislation. Educational measures should be targeted at groups known to
      be low users such as drivers and passengers in taxis, children carried on school
      'delivery trips' and adults in rear seats.

PMID- 8290688
TI  - The potential for changing the health care system within the current Polish
      transformations.
AB  - The health care system in Poland is characterised by central planning, by lack of
      separation of the preventive function and by being financed by the state. The
      author proposes a new approach which is now feasible within the framework of a
      democratic, elected government. Certain factors are proposed which will create a
      different and more effective health care system responsive to local need. These
      factors include separation of preventive and therapeutic functions, the provision
      of both public and private health insurance and local determination of needs and
      services.

PMID- 8290689
TI  - Cataract surgery in South West Thames Region: an analysis of age-adjusted surgery
      rates and length of stay by district.
AB  - Although the frequency of cataract surgery has increased in the UK, the demand is
      still not being met. There is no evidence of whether Regional Health Authorities
      are meeting the national target of 150 cataract operations per 100,000
      population. This paper describes variations in age-standardised rates of cataract
      surgery and lengths of hospital stay (LOS) between the 13 health districts in
      South West Thames Regional Health Authority (SWTRHA). A retrospective analysis of
      cataract surgery performed on South West Thames (SW Thames) residents during 1990
      was undertaken using the Korner hospital activity data system. The residents of
      SW Thames Region had 6,729 cataract operations in 1990, producing an overall
      surgery rate of 266 per 100,000 resident population. Two-thirds of the operations
      were performed on women, and the greatest number of operations were in the 75-79
      and 80-84 year age bands. Women aged over 75 had significantly higher age
      specific surgery rates than their male counterparts. The mean age for women was
      76.6 years and for men 71.9 years; 12% of cases had a length of stay less than a
      day (day cases) and 49% were discharged within two days. There were substantial
      variations in LOS between health districts. Age-adjusted rates revealed
      significant variations between districts, four of which had rates below the
      regional average. The crude cataract surgery rate for SW Thames residents has
      increased threefold since 1975. Women have a significantly higher rate of
      surgery, which may be due to social factors. Variations in LOS between districts
      cannot be explained by difference in age structure and may be caused by local
      custom and practice. It is possible for national, regional and district cataract
      rates to be calculated, and they are a useful indicator of how the need for
      cataract surgery is being met in the population.

PMID- 8290690
TI  - Access to plastics: assessing the need for plastic surgery services.
AB  - OBJECTIVE: To investigate the apparently poor access of one district's residents
      to plastic surgery services. DESIGN: Retrospective study of age-standardised
      operation rates for the year 1991-92. Operation rates were taken as a proxy
      measure for access. SETTING: Sunderland District Health Authority, and Durham
      District Health Authority. MAIN OUTCOME MEASURES: Operation rates for surgical
      specialties in the two districts. RESULT: There were considerable differences in
      the operation rates for plastic surgery between districts in the Region. Detailed
      analysis of two districts revealed a significant difference between the two
      (Sunderland 2.25/1,000; Durham 4.24/1,000, P < 0.001). Sixteen diagnoses were
      identified as contributing to this difference. However, when these diagnoses were
      examined across all surgical specialties, the difference in operation rates
      virtually disappeared (Sunderland 6/1,000; Durham 6.16/1,000). CONCLUSION:
      Sunderland residents were far more likely to have 'plastic' cases treated by
      other than plastic surgery specialists, which reflects the balance and expertise
      of specialties in the district. The need for plastic surgery services will be
      affected by the local interest and expertise. Operation rates should not be used
      on their own to indicate inequity in access.

PMID- 8290691
TI  - Relationships between habitual physical activity and osteoarthrosis in ageing
      women.
AB  - The examination of middle-aged women specialist teachers of physical education,
      who have undertaken habitual physical activity over many years, demonstrated a
      lower prevalence of osteoarthrosis in the knee joints, a greater prevalence of
      degenerative joint disease in the lumbar spine and a similar prevalence of
      osteoarthrosis in the hips, compared with a closely age-matched group. A further
      review 12 years later revealed significantly less joint pain and joint stiffness
      in active women compared with less active controls.

PMID- 8290692
TI  - MR imaging compared with CT, angiography, and myelography supplemented with CT in
      the diagnosis of spinal tumors.
AB  - To clarify the significance of MR imaging and the present status of CT,
      angiography, and myelography supplemented by CT (M-CTM), the radiological
      findings of 50 spinal tumors were reviewed and analyzed. MR imaging was most
      effective for visualizing morphological features such as the margins and/or inner
      structures of the tumors. CT was also effective for imaging "dumbbell" neurinomas
      and extradural tumors. Angiography was necessary in one hemangioblastoma and in
      cervical extradural tumors. M-CTM visualized the morphology of intradural
      extramedullary tumors and extradural tumors, but provided no new information in
      most of these cases. It was concluded that when using MR the indications for CT,
      angiography, and M-CTM are limited and that CT or angiography should be performed
      only in selected cases. M-CTM appeared to be unnecessary.

PMID- 8290693
TI  - Efficacy of emulsion containing Gd-DTPA and lipiodol in hepatic transcatheter
      arterial embolization.
AB  - We evaluated the clinical efficacy of an embolizing emulsion produced by mixing
      lipiodol and Gd-DTPA, in transcatheter arterial chemoembolization (TAE). Subjects
      were 10 patients with hepatocellular carcinoma (HCC). The emulsion used was
      produced by mixing 3 ml of lipiodol and anticancer agents (mitomycin-C 10 mg and
      adriamycin 20 mg) dissolved in Gd-DTPA. This emulsion was infused into the proper
      hepatic artery. Subsequent embolization by Gelfoam was performed in eight
      patients. MRI and CT examinations were performed soon after TAE (1 or 2 days
      after) and two weeks afterwards. The position of lipiodol accumulation dipicted
      on CT at two weeks after TAE did not differ from the site of change in signal
      intensity induced by Gd-DTPA on MR images soon after TAE in any case. In almost
      all cases, the washout of Gd-DTPA occurred earlier than that of lipiodol. It
      might be suggested that Gd-DTPA, which is water-soluble, shows in vivo dynamics
      similar to anticancer agents rather than to lipiodol, which is oil-soluble. Since
      the normal tissues showed no definite signal changes, we could easily detect the
      site of tumors by using the emulsion containing Gd-DTPA even on MR studies
      immediately after TAE. In addition, the deposits of Gd-DTPA depicted on MR images
      created fewer artifacts than the lipiodol deposits on CT.

PMID- 8290694
TI  - Preliminary study of pulmonary three-dimensional time-of-flight MR angiography
      with breath-holding using a contrast medium.
AB  - Pulmonary three-dimensional (3D) time-of-flight (TOF) MR angiography with breath
      holding using a paramagnetic contrast medium and a 1.5 Tesla superconducting MR
      system was performed on a volunteer and five patients with hilar or mediastinal
      tumors in order to visualize the main pulmonary arteries. Six MR scans (one
      before and five after a Gd-DTPA injection) were obtained using fast imaging with
      a steady-state precession (FISP) sequence while the subjects held their breath.
      The acquisition time was 21 seconds, and images were obtained every 30 seconds.
      In the normal volunteer, the pulmonary MR angiogram obtained in the first
      postcontrast scan was successful in visualizing the main pulmonary artery, and
      its right and left branches to the level of the lobar branches. In the five
      patients, at the first postcontrast scanning, the pulmonary arteries had higher
      signal intensities than the surrounding structures. Therefore, during this
      imaging period, most tumors could be clearly distinguished from vessels. In
      images made much later after contrast medium injection, the pulmonary arteries
      could not be distinguished from the others. Pulmonary 3D TOF MR angiography with
      breath-holding using a contrast medium is very useful in demonstrating pulmonary
      vessels and tumors.

PMID- 8290695
TI  - Direct cavernous sinus sampling.
AB  - To evaluate the potential of superselective cavernous sinus (CS) sampling in
      patients with functioning pituitary adenomas, we performed direct CS sampling in
      18 patients with Cushing syndrome and other functioning adenomas using a mini
      catheter. Samples from the inferior petrosal sinuses (IPS) were also obtained.
      All of the samples from 20 CS of 10 patients with Cushing syndrome and 13 of 16
      samples from CS of eight patients with other adenomas were successfully obtained.
      No complication occurred. In three patients, the mini-catheter was introduced to
      the contralateral CS through intercavernous communication, and bilateral sampling
      could be performed via the unilateral jugular vein. The CS/peripheral (CS/P)
      ratio of ACTH (mean = 66.1) was significantly greater than the IPS/peripheral
      (IPS/P) ratio (mean = 14.9) in Cushing disease. In other functioning adenomas,
      the CS/P ratio (15.8) was not significantly higher than the IPS/P ratio (4.8).
      Direct CS sampling offers a much higher CS/P ratio than IPS/P ratio in Cushing
      disease, and may provide sufficient diagnostic accuracy without CRH stimulation
      or bilateral simultaneous sampling.

PMID- 8290696
TI  - Cine MRI in radiotherapy treatment planning of brain tumors.
AB  - This paper presents our preliminary experience with three-dimensional (3-D)
      treatment planning using the cine mode display of magnetic resonance imaging
      (MRI) for brain tumors. MRI images, viewed from the direction of the source of
      radiation, are reconstructed at consecutive 5 mm intervals and superimposed on
      the 3-D skin surface image. Tumors and normal structures can be visualized as is,
      without delineating them. Limitations of the technique are also discussed.

PMID- 8290697
TI  - Radiotherapy for mediastinal obstruction and intrathoracic lymphadenopathy in
      chronic lymphocytic leukemia.
AB  - Four of 65 patients (6%) with chronic lymphocytic leukemia (CLL) were treated by
      megavoltage teleradiotherapy for palliation of symptoms arising from mediastinal
      obstruction or intrathoracic lymphadenopathy. External beam irradiation was found
      to be effective treatment for these disease complications associated with CLL.

PMID- 8290698
TI  - A case of intracranial involvement of Hodgkin's disease.
AB  - We report a rare case of Hodgkin's disease in which intracranial involvement
      developed during the course of the patients illness. A 20-year-old man who had
      complained of lymph node swelling on the right neck was admitted to a hospital in
      December 1978. Lymph node biopsy revealed Hodgkin's disease, and he was treated
      by various series of chemotherapy and radiotherapy with unsatisfactory results.
      He was transferred to Yamanashi Medical College Hospital in June 1985. He was in
      a far-advanced state at the time, and palliative treatment was applied. In the
      middle of May 1986, he complained of headache, tinnitus, and sleeplessness.
      Vomiting and tremor were observed by the end of May 1986. Brain CT scan revealed
      a space occupying lesion in the right temporal region. Whole brain irradiation of
      45 Gy was effective, and the lesion disappeared. However, his general condition
      deteriorated and he died in November 1986. Brain autopsy could not be performed.

PMID- 8290699
TI  - Delayed imaging of Tc-99m-DTPA-HSA SPECT in subacute cerebral infarction.
AB  - Cerebral blood volume measurement by Tc-99m-DTPA-HSA SPECT was performed in a
      patient with subacute cerebral infarction to evaluate compensatory
      vasodilatation. Additional delayed imaging revealed focal increased radioactivity
      that was not found on the early images, indicating leakage of radioactive agents
      due to blood-brain barrier breakdown. Delayed SPECT may be helpful to detect
      areas unsuitable for estimating regional blood volume.

PMID- 8290700
TI  - Exophytic pontine glioma mimicking acoustic neurinoma: CT and MRI appearance.
AB  - A 31-year-old female having a family history of neurofibromatosis 1 presented a
      left CPA tumor. MRI findings showed a completely extraaxial tumor, suggesting an
      acoustic neurinoma except for the lesion in the acoustic meatus. However, the
      final diagnosis was of exophytic pontine glioma. When a CPA tumor shows no lesion
      in the internal acoustic meatus, the possibility of exophytic pontine glioma
      should be considered in the differential diagnosis, especially in NF-1 patients.

PMID- 8290701
TI  - Effect of prednisolone on renal scarring in rats following infection with
      Serratia marcescens.
AB  - Renal scarring is considered a criterion of reflux nephropathy and the end stage
      of pyelonephritis. Prednisolone, a strong anti-inflammatory drug, at doses of 1
      or 2 mg/kg prevented renal scarring in rats following infection with Serratia
      marcescens. Four or 8 mg/kg of prednisolone, however, did not inhibit renal scar
      formation. In a time course experiment, renal scarring was prevented when 4-day
      treatment with prednisolone was initiated 2, 5, or 13 days after infection. These
      results show that prednisolone is effective in preventing such scarring and
      suggest the clinical use of this drug for preventing renal scar formation after
      pyelonephritis and reflux nephropathy.

PMID- 8290702
TI  - Protein-restricted diet prior to renal insult improves the recovery of renal
      function following ischemia.
AB  - The effects of a protein-restricted diet on renal recovery following renal
      ischemia were studied. The renal function was assessed by measuring the inulin
      clearance (CIN), the p-aminohippurate clearance (CPAH), and the percent
      fractional sodium excretion (%FENa) 24 h after 45 min renal ischemia. In rats fed
      with a regular diet (containing 19.6% protein), CIN was 10.0 +/- 2.2
      microL/min/100 g body weight (BW), CPAH 0.08 +/- 0.02 mL/min/100 g BW, and %FENa
      14.8 +/- 2.0, 24 h after renal ischemia. In contrast, feeding rats with a no
      protein diet (0% protein) for 1 week prior to the ischemic insult significantly
      improved renal recovery (CIN 48.0 +/- 9.3 microL/min/100 g BW, CPAH 0.16 +/- 0.04
      mL/min/100 g BW, and %FENa 2.43 +/- 0.58). Feeding rats with a no-protein diet
      for 3 weeks prior to ischemic insult further improved the renal recovery (CIN 113
      +/- 30 microL/min/100 g BW, CPAH 0.47 +/- 0.17 mL/min/100 g BW, and %FENa 1.55 +/
      0.29). When rats fed with a regular diet were exposed to 45 min of ischemia, the
      survival rate on day 7 was 16.7%. In rats fed with the no-protein diet for 1 week
      and for 3 weeks, the 7-day survival rate was 100% in each case. The survival rate
      of rats fed for 3 days instead of 7 days with the no-protein diet was 87.5%. When
      a no-protein feeding was shortened to 1 day, no beneficial effects were observed
      and survival rate was 14.3%. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290703
TI  - Transplantation of warm ischemia damaged kidneys: an experimental study in pigs.
AB  - This study evaluated renal function and histological and oxidative injury in
      transplanted kidneys harvested after prolonged warm ischemia in pigs. In 8 donor
      pigs, kidneys were perfused in situ 120 min after cardiac arrest. One of each
      pair of kidneys was used for histological and biochemical studies while the other
      was transplanted into a recipient undergoing bilateral nephrectomy. In 6 cases,
      renal function was satisfactory 14 days after transplantation. Histologically, a
      reversible acute tubular necrosis was observed with partial recovery at the 14th
      postoperative day. A moderate oxidation was revealed by decreased glutathione and
      increased malondialdehyde levels. In spite of this ischemic injury, these
      findings suggest that kidneys harvested after prolonged warm ischemia can still
      recover after transplantation, and that non-heart-beating donors may be
      considered as an alternative organ source for kidney transplantation.

PMID- 8290704
TI  - Postischemic recovery process of renal oxygen consumption in normal and
      streptozotocin diabetic rats.
AB  - We tried to study in depth the recovery process in the cortical and the medullary
      oxygen (O2) consumption of normal and streptozotocin diabetic rat kidneys after
      ischemia. It was found that the cortical and the medullary O2 consumption
      decreased after ischemia, reaching their lowest levels at 1 day after every
      ischemic duration in normal and diabetic kidneys. In the period prior to ischemia
      to 1 day after ischemia, no significant difference was seen in the decrease in O2
      consumption between the cortex and the medulla in normal kidney, whereas the
      medullary O2 consumption significantly decreased compared with the cortical O2
      consumption in diabetic kidney. From 1 day to 4 weeks after ischemia, the
      increase in the cortical O2 consumption was significantly higher than that in the
      medulla of normal kidney. In contrast, the increase in the medullary O2
      consumption was significantly higher than that in the cortex of diabetic kidney.
      Consequently, up to 4 weeks after ischemia, the decrease in the cortical O2
      consumption was significantly lower than in the medulla of normal kidney, while
      there was no significant difference regarding the decrease in O2 consumption
      between the cortex and the medulla in diabetic kidney. These results suggest that
      there is a clear difference in the postischemic recovery process of O2
      consumption between the cortex and the medulla, and also between normal and
      diabetic rat kidneys.

PMID- 8290705
TI  - A comparison of conventional dialytic therapy and acute continuous
      hemodiafiltration in the management of acute renal failure in the critically ill.
AB  - OBJECTIVE: To compare and contrast the clinical outcomes in critically ill
      patients with acute renal failure managed with either acute continuous
      hemodiafiltration or conventional dialytic therapies. DESIGN: Retrospective
      review of the medical records of 167 consecutive cases of acute renal failure
      treated at a single center (July 1982-July 1991). Scoring for illness severity
      (APACHE II, number of failing organs) and assessment of outcome in terms of
      biochemical control of azotemia, ARF therapy-related morbidity, and overall
      morbidity and mortality. SETTING: Tertiary institution. PATIENTS: 167 consecutive
      critically ill patients with multiorgan failure and acute renal failure.
      MEASUREMENTS AND MAIN RESULTS: 84 patients received conventional dialytic therapy
      (CDT) (1982-1988) and 83 acute continuous hemodiafiltration (ACHD) (1988-1991).
      The etiology of ARF and illness severity indices were similar in both groups
      (organ failure scores: CDT 3.9 vs. ACHD 4.1; NS). All patients were critically
      ill, with more severely ill patients within the ACHD groups (mean APACHE II
      score: CDT 25.8 vs. ACHD 28.1; p < .01). There were no significant differences in
      pretreatment serum creatinine, glucose, bicarbonate and phosphate, white cell and
      platelet counts, incidence of disseminated intravascular coagulation, prevalence
      of sepsis, or evidence of pulmonary and/or peripheral edema. Overall survival was
      29.8% for the CDT groups and 41% for the ACHD group (NS). When patients were
      stratified by severity of illness, survival in those with 2 to 4 failing organs
      was significantly greater in the ACHD group (CDT 31.1% vs. ACHD 53.8%; p < .025).
      Similarly, overall survival in patients with intermediate APACHE II scores (24 to
      29) was significantly better in those treated with ACHD (CDT 12.5% vs. ACHD
      46.4%; p < .025). During the course of ARF, in comparison to CDT, ACHD was
      associated with greater overall reductions in serum creatinine, and in phosphate
      and plasma urea, and an increased net nutritional intake. CONCLUSIONS: ACHD
      provided biochemical and outcome indicator advantages over conventional dialytic
      therapy. In patients with 2 to 4 failing organs or an intermediate APACHE II
      score (24 to 29) a significant survival advantage was demonstrated for ACHD over
      CDT. Although this study is a retrospective analysis, with all the inherent
      limitations of such studies, it suggests that ACHD is the treatment of choice for
      ARF in the critically ill, with maximum benefits seen in those with 2 to 4
      failing organs and/or intermediate APACHE II scores.

PMID- 8290706
TI  - Outcome of acute renal failure in adults in a teaching hospital in Bangladesh.
AB  - One hundred and twenty patients with a mean age of 38 years (range 12-85 years; M
      91, F 37) were studied over a period of 5 years in a teaching hospital in Dhaka.
      Sixty-two patients presented with probable anuria with 1-4 days' duration, 63
      patients presented with oliguria, and 3 were nonoliguric. The causes of acute
      renal failure were medical (94), surgical (22), obstetrical (13). Of the medical
      cases, the causes were gastroenteritis in 42 cases, gastroenteritis with CNS
      involvement in 11 cases, rapidly progressive glomerulonephritis in 10 cases,
      acute viral hepatitis in 8 cases, and septicemia in 8 cases. Of 22 surgical
      cases, postoperative acute renal failure was the cause in 9, road traffic
      accident in 6, and renal calculus disease in 7. There were 13 cases in the
      obstetrics group, of whom 9 were due to abortion, 2 were due to preeclampsia, and
      the other 2 were postoperative. The mean blood urea of all cases was 35 mmol/L
      and serum creatinine was 988 mumol/L. Dialysis was required in 105 cases; of
      these, 72 were medical cases, 21 were surgical cases, and 12 were obstetric
      cases. The overall survival rate was 75%. The improved survival is probably due
      to timely referral and prompt medical management.

PMID- 8290707
TI  - Acute renal failure in pregnancy.
AB  - Between 1982 and 1992, 18 cases of pregnancy-related acute renal failure (PR-ARF)
      were observed (9% of the total number of ARF). Mean age of the women was 32 years
      (22-40 years). Uterine hemorrhage and preeclampsia/eclampsia were the major
      causes of ARF, accounting for 61% of the cases. Patchy renal cortical necrosis
      was suspected in 2 cases whereas signs of disseminated intravascular coagulation
      (DIC) or microangiopathic hemolytic anemia were present in 6 (33%) and 9 (50%)
      cases, respectively. Ten women required hemodialysis; and 6 of them, additional
      plasma exchange sessions. Five patients (28%) died during the acute phase of the
      illness, mainly due to brain damage, hepatic failure, and sepsis. Among the
      survivors, a complete (61.5%) or partial recovery (23.1%) was usually seen, but
      irreversible renal failure was recorded in 2 cases with postpartum hemolytic
      uremic syndrome (HUS). Short-lasting oligoanuria (< 3 days) represents a good
      prognostic index. However, the presence of vascular injury (cortical necrosis,
      HUS) seems to carry a poor prognosis. In conclusion, PR-ARF is still a critical
      occurrence, associated with serious prognosis for both women and kidneys. So far,
      the most effective measures remain the careful prevention and the aggressive
      management of the obstetric complications.

PMID- 8290708
TI  - The effects of angiotensin-converting enzyme inhibitors on the clinical and
      biochemical parameters in diabetic nephropathy.
AB  - Captopril's short-term effects on clinical and biochemical parameters were
      studied in 21 diabetic nephropathic patients. Their mean age was 57.50 +/- 2.28
      years; 16 of them were women and 5 were men. Eleven patients had been regulated
      with insulin and 10 of them had been regulated with oral antidiabetics. Fifteen
      patients were microalbuminuric (200 mg/daily and below albuminuria) and their
      mean diabetes mellitus history was 14.86 +/- 1.44 years. Six patients had
      advanced diabetic nephropathy (400 mg/daily and above albuminuria). Their mean
      diabetes mellitus history was 4.50 +/- 2.87 years. Captopril in a low dose (37.5
      mg/daily p.o., three separated doses) was given during 20 days. In the
      microalbuminuria group there were insignificant alterations in renal function,
      blood glucose levels, and systolic blood pressure. Diastolic blood pressure
      decreased significantly in this group (p < .05). Microalbuminuria increased
      significantly after the therapy in this group (p < .05). In the advanced diabetic
      nephropathy group, blood glucose and systemic blood pressure levels did not
      change significantly (p > .05), while serum BUN and creatinine levels increased
      significantly (p < .05), and GFR decreased significantly in this group (p < .05).
      Albuminuria decreased after the therapy in this group (p < .05). In all study
      groups, serum potassium levels increased significantly while serum total protein
      and albumin levels did not change significantly.We concluded that in the
      microalbuminuria group, increasing microalbuminuria may be related to a captopril
      induced increase in renal plasma flow rate and single nephron glomerular
      filtration rate. This increase in microalbuminuria cannot be related with blood
      glucose levels, renal functions, and systemic blood pressure
      alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290709
TI  - Transplantation for renal amyloidosis.
AB  - Renal transplantation therapy performed for amyloid nephropathy is controversial
      because of the fatal effects of the disease. Amyloidosis is a relatively frequent
      disease and is generally associated with familial Mediterranean fever (FMF) in
      Turkey. Renal transplantation in the treatment of amyloid nephropathy started in
      January 1985. Till now, 18 (3.2%) renal transplantations have been performed on
      patients who had amyloid nephropathy. The mean follow-up period was 34.6 months.
      Fourteen renal grafts still function well (creatinine: 1-3.2 mg/dL). The overall
      1-year patient and graft survival rates were 88.9% and 83.0%, respectively. These
      rates are not statistically different from renal transplantations done for other
      cases of renal failure. Therefore, patients with end-stage renal failure due to
      amyloidosis can be considered as appropriate candidates for renal
      transplantation.

PMID- 8290710
TI  - Acute renal failure due to acute rhabdomyolysis precipitated by MAST trousers and
      diflunisal.
AB  - This report describes a patient who developed acute rhabdomyolysis and acute
      renal failure following the application of MAST trousers associated with an
      overdose of diflunisal. This association has not previously been reported.

PMID- 8290711
TI  - Acute renal failure due to ingestion of the gallbladder of grass carp: report of
      3 cases with review of literature.
AB  - Gallbladder toxin of the grass carp (Ctenopharyngodon idella) is a less well
      known cause of acute renal failure. Three cases are reported and the diagnosis is
      primarily clinical. All our patients presented initially with gastrointestinal
      upset including nausea, vomiting, diarrhea, and abdominal fullness. These
      symptoms usually occurred with 10 min to 18 h after the ingestion the raw
      gallbladder of the grass carp. All our cases developed acute renal failure and in
      two of them toxic hepatitises were noted. An acute tubular necrosis was
      demonstrated on renal biopsy in one of our patients. The treatment is mainly
      supportive and two of them received hemodialysis. All three cases recovered, with
      normal renal and liver functions 2-4 weeks after the incident. A review of the
      cases previously reported in the English literature is presented.

PMID- 8290712
TI  - Acute sodium chlorite poisoning associated with renal failure.
AB  - A 25-year-old Chinese male presented with generalized cyanosis and respiratory
      distress. The patient was known to have ingested 10 g of sodium chlorite in a
      suicide attempt. Methemoglobinemia was found and intravenous methylene blue was
      given repeatedly. However, the therapy could not prevent an acute hemolytic
      crisis. Methemoglobinemia remained profound (43.1%) and disseminated
      intravascular coagulation ensued. He was put on CAVHD to correct the fluid
      overload and probably to remove the active metabolites of the chlorite. After 24
      h, the methemoglobin was reduced to 16.9%. However, the development of acute
      renal failure further complicated the clinical course. Percutaneous renal biopsy
      suggested a picture of acute tubulointerstitial nephropathy. In addition,
      hemodialysis was continued for 4 weeks. After 3 months, renal function
      normalized. To our knowledge, there has been no clinical report of human
      intoxication with sodium chlorite.

PMID- 8290713
TI  - Renal cell carcinoma in patients with acquired cystic renal disease. A case
      report.
AB  - A patient with renal cell carcinoma in primitive kidney with acquired cystic
      renal disease following hemodialysis for 9 years was discovered during a routine
      ultrasonographic follow-up. Differences with these tumors in transplanted
      patients are stressed.

PMID- 8290714
TI  - Hemlock poisoning, acute renal failure, and the Bible.

PMID- 8290715
TI  - Intradermal hepatitis B vaccination in nonresponsive hemodialysis patients.

PMID- 8290716
TI  - And the greatest of these is communication.

PMID- 8290717
TI  - Electronic media for education and communication in radiology: the saga
      continues.

PMID- 8290718
TI  - Outcomes research: challenges for the 1990s.

PMID- 8290719
TI  - Puncture of the portal bifurcation: a fatal complication of TIPS.

PMID- 8290720
TI  - Complications of transjugular intrahepatic portosystemic shunt: a comprehensive
      review.
AB  - It is generally accepted that the transjugular intrahepatic portosystemic shunt
      (TIPS) procedure has lower morbidity and mortality rates than those of surgical
      shunting. Nevertheless, complications occur. The authors have reviewed their
      experience and that of other institutions in compiling an extensive list of
      complications. Complications are categorized according to those related to
      transhepatic needle puncture, transvenous access to the portal vein, portal
      venous cannulation, the stent, the puncture site, portosystemic shunting, and
      contrast material. Excluding hepatic encephalopathy and delayed stenosis or
      occlusion of the shunt, an overall complication rate of less than 10% can be
      expected for TIPS. The prevalence of aggravated or new cases of encephalopathy is
      5%-35%, and over the long term, up to 75% of shunts may undergo stenosis or
      occlusion. The direct procedural mortality rate is less than 2%, and the 30-day
      mortality rate ranges from 4% to 45%, depending on several factors. The role to
      which TIPS is relegated will be influenced by the long-term success rate in the
      prevention of recurrent variceal hemorrhage.

PMID- 8290721
TI  - MR imaging of anatomy and tears of wrist ligaments.
AB  - Numerous intrinsic and extrinsic wrist ligaments are visible at magnetic
      resonance (MR) imaging. Because the previously published descriptions of these
      ligaments were often conflicting, the authors derived a classification system
      based on a functional perspective and their experience with MR imaging,
      arthroscopy, and surgical dissection. This system was used to evaluate MR images
      of 23 cadaveric wrists for the presence and integrity of 16 wrist ligaments. MR
      images were prospectively analyzed by two observers, and all findings were
      correlated with the results of arthroscopy. The best detection rates and
      diagnostic confidence rates were achieved for the triangular fibrocartilage (100%
      and 100%, respectively) and the scapholunate ligament (91% and 87%,
      respectively). Other ligaments were less well seen, partly because of their size
      and course. Eighty-two percent of the triangular fibrocartilage tears, 50% of the
      scapholunate tears, and 40% of the lunotriquetral tears seen at arthroscopy were
      detectable on MR images. Identification of these three types of tears on MR
      images is important because they are functionally significant and because there
      are accepted methods of treating them in orthopedic practice.

PMID- 8290722
TI  - Percutaneous management of hilar biliary malignancies with metallic
      endoprostheses: results, technical problems, and causes of failure.
AB  - Malignant obstruction at the biliary hilum is a challenging problem for
      percutaneous management because of the anatomy of the biliary hilum, which
      facilitates spread of tumor into multiple biliary radicles. Metallic self
      expanding stents were used in 22 patients with hilar malignancies. Sixteen
      patients had focal common hepatic duct strictures, and six had multisegmental
      disease. Stents were placed in the biliary system with a single transhepatic
      approach in 16 patients with common hepatic duct strictures; stent placement in
      the right and left biliary ducts was performed with a bilateral transhepatic
      approach in five patients and with a single transhepatic approach in one patient.
      Metal stent occlusion occurred in six patients (27%) at a mean of 2.5 months
      after initial insertion. Stent occlusion was due to inspissated debris in two of
      these patients and to tumor overgrowth in four. The key to successful long-term
      treatment is to "overstent" to ensure adequate purchase above hilar tumors and
      insertion in a balanced position. Thus, the prevalence of tumor overgrowth is
      decreased.

PMID- 8290723
TI  - Differential diagnosis of fat-containing lesions with abdominal and pelvic CT.
AB  - Recognition of fat within an organ or lesion on abdominal and pelvic computed
      tomographic scans is an important clue to guiding a differential diagnosis. A
      systematic approach to these lesions, including a patient's age and clinical
      history, along with the appearance and location of the lesion often allows a
      specific differential diagnosis. The anatomic sites of origin for these lesions
      are the gastrointestinal tract, genitourinary system, and retroperitoneum. Some
      of the more common entities include various forms of fatty change in the liver,
      fibrofatty mesenteric proliferation in Crohn disease, ovarian dermoids, and
      herniations of abdominal fat. In addition, pitfalls such as pathologic processes
      engulfing normal fat (eg, perirenal abscess) and iatrogenic incorporation of
      normal fat (eg, omental packing in liver lacerations) should also be included in
      the differential diagnosis. Familiarity with certain benign occurrences, such as
      focal fat in the liver adjacent to the falciform ligament and lipomatous
      infiltration of the ileocecal valve, obviates invasive diagnostic procedures.

PMID- 8290724
TI  - Color Doppler US of children with acute lower abdominal pain.
AB  - The authors review the color Doppler ultrasonographic (US) features of
      appendicitis and other diseases that can manifest with acute lower abdominal
      pain. Causes of acute abdominal pain, other than appendicitis, include
      gynecologic abnormalities (ovarian cyst, ovarian torsion, pelvic inflammatory
      disease), gastrointestinal abnormalities (infectious enteritis, Crohn disease,
      mesenteric lymphadenitis, intussusception), and urinary tract diseases. On color
      Doppler images, inflammatory and infectious processes usually show locally
      increased blood flow, whereas cysts and twisted masses have absent blood flow.
      Enlarged lymph nodes also are avascular. Color Doppler US is a useful adjunct to
      gray-scale US in evaluating acute lower abdominal pain in children and can aid in
      defining and clarifying gray-scale abnormalities.

PMID- 8290725
TI  - CT evaluation of amyloidosis: spectrum of disease.
AB  - Amyloidosis is a rare systemic disease caused by extracellular deposition of an
      insoluble protein. Although it is usually seen in a systemic form, 10%-20% of
      cases can be localized. Systemic amyloidosis is subclassified into an idiopathic
      primary form and a secondary or reactive form. Patients with primary amyloidosis
      have no underlying condition or disease. Men are affected more than women, and
      the mean age at presentation is 55-60 years. Some causes of secondary amyloidosis
      are multiple myeloma (10%-15%), rheumatoid arthritis (20%-25%), tuberculosis
      (50%), or familial Mediterranean fever (26%-40%). Radiographic studies of 90
      patients with biopsy-proved primary or secondary amyloidosis were reviewed.
      Computed tomographic (CT) scans demonstrated a wide spectrum of disease in the
      cardiothoracic, gastrointestinal, genitourinary, and musculoskeletal systems.
      Amyloid deposition simulated both inflammatory and neoplastic conditions.
      Amorphous or irregular calcifications were occasionally identified within the
      amyloid deposit. Definitive diagnosis requires biopsy confirmation, as CT
      findings are nonspecific.

PMID- 8290726
TI  - CT of the mesocolon. Part 2. Pathologic considerations.
AB  - The anatomy of the mesocolon can be seen on computed tomographic (CT) scans, and
      its CT anatomy can be described by using the vessels in the mesocolon as anatomic
      landmarks. Knowledge of this anatomy is the basis to understanding pathologic
      processes involving the mesocolon. Common pathologic conditions usually occur due
      to spread of disease between organs to which the mesocolon is attached, primarily
      the colon and pancreas. The disease may be a malignant lesion, a benign
      inflammatory process, or, rarely, a primary tumor of the mesocolon; the mode of
      spread may be via the lymphatic vessels, direct extension, vascular invasion, or
      vascular involvement. The authors demonstrate various pathologic conditions and
      modes of spread, as seen on CT scans, with emphasis on disease of the colon and
      pancreas. The pathway for the spread of disease and its progression in these
      organs can be predicted in patients with a known disease. More important,
      identification of abnormalities in the mesocolon leads to careful evaluation of
      the organs to which the mesocolon is attached.

PMID- 8290727
TI  - Diagnosing breast implant rupture with MR imaging, US, and mammography.
AB  - A total of 135 symptomatic women with 262 breast implants were examined with
      magnetic resonance (MR) imaging performed with a body coil, ultrasound (US), or
      both to determine imaging features of implant rupture. Surgical proof was
      available for 33 women with 62 implants; 24 were ruptured and 38 were intact.
      Complicated internal structure was the most reliable predictor of implant
      rupture: Diffuse low-level echoes were seen on sonograms in 56% of ruptured
      implants; internal membranes (which correspond to the collapsed implant shell)
      were seen on MR images in 58% of ruptured implants. Fluid droplets were seen
      within the silicone in 26% of ruptured implants on MR images. Irregular implant
      contour can be a sign of rupture but is unreliable. Fluid collections around
      silicone implants are not a sign of rupture. At present, neither US nor
      conventional MR imaging with a body coil is sufficiently reliable to advocate
      routine screening of asymptomatic women with breast implants. Evaluation with MR
      imaging performed with a surface coil is more reliable.

PMID- 8290728
TI  - Factors affecting x-ray spectra.
AB  - The x-ray spectrum is defined as the energy distribution of the radiation
      produced in an x-ray exposure. The x-ray spectrum has a major impact on image
      quality and radiation dose delivered to patients. The authors explored the
      effects of three key factors on x-ray spectra: generator type, peak tube
      potential, and filtration. Different generator types are characterized by the
      amount of ripple in the kilovoltage waveform. Those with high (100%) ripple such
      as single-phase units produce less penetrating radiation than units with low (4%)
      ripple such as three-phase, 12-pulse generators. As peak tube potential
      increases, the half-value layer increases nearly linearly; radiation output
      increases by approximately the square of the tube potential. Filtration materials
      with atomic numbers less than 42, such as aluminum, titanium, copper, and
      niobium, produce similar spectra, with only slight variations in efficiency.
      Although aluminum has the lowest efficiency, this may be compensated for by
      increasing milliampere seconds. Filtration in addition to the inherent filtration
      provided by the tube reduces both skin surface dose and average depth-dose, with
      the optimal amount being approximately 2-3 mm or less of aluminum-equivalent
      material.

PMID- 8290729
TI  - Embolization in the treatment of acquired and congenital abnormalities of the
      heart and thorax.
AB  - Embolization is well suited to the treatment of a range of vascular abnormalities
      found only in the thorax. This includes congenital arteriovenous fistulas or
      malformations affecting the chest wall and the pulmonary and coronary arteries.
      Acquired bronchial artery anomalies and some types of congenital heart disease
      are also suitable for embolization. Embolization in the thorax presents problems
      related to the need to work through or in the heart or to the risk to important
      branches of the intrathoracic aorta, such as the carotid arteries. The choice and
      use of different catheters and embolic materials for thoracic embolization depend
      on the nature and configuration of the lesion and the experience of the operator.
      Selection must also be based on consideration of the risk of inadvertent
      embolization of adjacent structures such as the spinal arteries. With
      embolization experience elsewhere in the body and an understanding of the
      particular problems presented by thoracic embolization, various important, even
      if uncommon, conditions can be effectively treated.

PMID- 8290730
TI  - Primary extragonadal germ cell tumors of the retroperitoneum: differentiation of
      primary and secondary tumors.
AB  - Primary extragonadal germ cell tumors (EGCTs) of the retroperitoneum are rarely
      encountered. In most cases, they arise from remnants of the genital ridge,
      whereas the majority of retroperitoneal germ cell tumors are metastases from
      primary testicular tumors. Differentiating between these primary and secondary
      tumors can be difficult because gonadal germ cell tumors can regress or develop
      slowly. Careful examination of the testes with ultrasound (US) is crucial for
      this determination, but asynchronous or metachronous lesions in both the testes
      and retroperitoneum can occur. Symptoms are often nonspecific, and diagnosis is
      frequently delayed. Serum markers such as beta-human chorionic gonadotropin and
      alpha-fetoprotein are often helpful in the diagnosis and follow-up of these
      tumors. Imaging techniques such as US and computed tomography play a major role
      in the localization and differentiation of primary and secondary retroperitoneal
      EGCTs. Treatment of EGCTs usually requires a combination of surgery, irradiation,
      and chemotherapy.

PMID- 8290731
TI  - Specifying DICOM compliance for modality interfaces.
AB  - For picture archiving and communication systems (PACS) to be successful, they
      must be able to acquire image data from imaging devices and integrate this
      information into a PACS data base. Substantial effort has been invested in the
      Digital Imaging and Communications in Medicine (DICOM) standard to define a
      standard network interface and data model for imaging devices that can facilitate
      information systems integration. A communication standard cannot ensure
      multivendor interoperability. Necessary implementation-specific requirements are
      beyond the scope of a standard but not of a user-generated conformance statement.
      A DICOM user conformance profile (UCP) is a formal statement drafted by a
      potential purchaser of medical imaging equipment to state clearly the subset of
      DICOM functionality that shall be provided by a potential vendor. The UCP
      specifies the service classes, information objects, and communication protocols
      to be supported by the implementation. A modality interface UCP presented by the
      author permits scheduling and demographic information to be communicated to an
      imaging modality and allows images to be stored in a PACS. The UCP also ensures
      an unambiguous notification of the end of a study and proper communication of
      image data.

PMID- 8290732
TI  - Instrumentation of digital gray-scale US.
AB  - Modern, high-resolution, gray-scale, ultrasound (US) imaging equipment is
      computer based, with all hardware signal processing functions under software
      control. This systems architecture permits maximum flexibility in function, rapid
      upgrades, and reliable performance. With modern US equipment, the spatial
      dimensions of the analog image are transformed into a digital matrix of picture
      elements (pixels). The volume of tissue, or voxel, that contributes to the echo
      amplitudes received from each pixel depends crucially on the section (ie,
      "slice") thickness at the voxel depth. Partial volume effects are more likely to
      occur in a longer voxel located at a depth outside the section thickness focal
      zone. The echo signal voltage, or amplitude, is acquired by an analog-to-digital
      converter simultaneously with the pixel location of the image echo origin. The
      most accurate echo amplitudes (with least partial volume averaging) occur at the
      highest image magnification when the voxel dimensions are the smallest in and out
      of the scan plane. With computer-based imaging, postprocessing procedures, such
      as fill-in algorithms and digital calipers (measurements of distances in images),
      can be used to aid in diagnosis.

PMID- 8290733
TI  - Pediatric case of the day. Primitive neuroectodermal tumor (PNET) of the right
      maxillary sinus.

PMID- 8290734
TI  - US case of the day. Median arcuate ligament syndrome (celiac artery compression
      syndrome).

PMID- 8290735
TI  - General case of the day. Idiopathic chylothorax.

PMID- 8290736
TI  - Ecotoxicology of selenium in freshwater systems.
AB  - The toxicology, environmental impacts and risk assessment of Se in freshwater
      systems are a high priority for research and regulatory agencies. However,
      understanding Se in freshwater systems is a challenging endeavor. The accurate
      risk assessment and determination of a water-quality criterion for any freshwater
      ecosystem are difficult for many reasons. First, the understanding of the
      structure and energy dynamics in ecosystems is limited. Second, knowledge of Se
      cycling and transformations in aquatic ecosystems is rudimentary. Third, the role
      of various environmental factors affecting its bioaccumulation,
      biotransformation, and toxicology in aquatic ecosystems is largely unknown.
      Fourth, the extrapolation and use of existing data in commonly used formulas for
      risk assessment and calculations of water quality criteria is difficult because
      of the demonstrated species differences in the bioaccumulation, metabolism, and
      tolerance of Se. There are many aspects of Se ecotoxicology that need to be
      addressed to develop more accurate environmental risk assessments and determine
      appropriate water-quality criteria to protect aquatic ecosystems. Studies
      evaluating the biochemical speciation of Se in aquatic ecosystems, and
      determination of the role of microbial communities in its cycling,
      bioaccumulation, transformation, transfer, and toxicity in aquatic systems,
      appear to be priorities for future research. These would include a broad
      exploration of Se effects on ecosystems, e.g., exposure regime, direct and
      indirect biologic effects, and ecosystem level effects. There are, however,
      ecological uncertainties that tend to confound such endeavors, e.g., insufficient
      data, extrapolation issues, and environmental stochasticity (Harwell and Harwell
      1989). There are several concepts concerning the ecotoxicology of Se that can be
      stated. Elevated concentrations have degraded many freshwater ecosystems
      throughout the United States, and additional systems are expected to be affected
      as anthropogenic activities increasingly mobilize Se into aquatic systems. Se is
      a very toxic essential trace element. Toxic threshold concentrations in water,
      dietary items, and tissues are only 2-5 times normal background concentrations.
      Toxicity in freshwater ecosystems is the result of bioaccumulation,
      biotransformation, and cycling of Se in aquatic food chains. Thus, environmental
      risk assessment and development of effective water-quality criteria to protect
      freshwater ecosystems become formidable tasks.

PMID- 8290737
TI  - Predicting ecotoxicological impacts of environmental contaminants on terrestrial
      small mammals.
AB  - This review examines whether the effects of environmental contaminants on wild
      small mammals can be predicted from the results of single-species, laboratory
      toxicity studies. Heavy metals, organochlorines, chlorinated aromatic
      hydrocarbons, and OP/carbamate pesticides were identified as the groups of
      xenobiotics for which there are toxicity data for terrestrial small mammals and
      that, on the basis of persistence, acute toxicity, and bio-accumulation
      potential, present the greatest hazard to wild mammals. Laboratory-generated
      toxicity data, which used lethality and reproduction as measurable endpoints,
      were reviewed and intake and residue LOAELs estimated for representative
      chemicals (lead, endrin, PCBs) from the heavy metal, organochlorine, and
      chlorinated aromatic hydrocarbon substance groups; the OPs and carbamates were
      reviewed as a whole. Intakes and residues of these compounds in wild small
      mammals were compared with laboratory-defined LOAELs and the likelihood of
      effects predicted. The accuracy of these predictions was examined and the
      efficacy of extrapolating toxicity data from laboratory to wild species assessed.
      Qualitative extrapolation from laboratory to wild species was good for all the
      chemicals considered, laboratory tests correctly identifying the types of effects
      chemicals had on a wide range of wild mammals. In contrast, the quantitative
      extrapolation of dose-response data was either poor or largely unvalidated. This
      is because interspecies variation in sensitivity to xenobiotics and the effects
      on toxicity of differences in exposure pattern between laboratory and wild
      species are largely unquantified. Based upon the limited evidence available,
      errors in the direct extrapolation of dose-response data from laboratory to field
      may be as large as three orders of magnitude. Direct extrapolation of residue
      response data from laboratory to wild mammals is good both for the effects of
      heavy metals on specific organs and for residues and acetylcholinesterase
      inhibition associated with pesticide-induced mortality. The use of organ residues
      or biomarkers to predict the severity of sublethal effects on reproductive output
      may be possible, although large residues or biomarker responses are not
      necessarily indicative of the severity of wider physiological effect. Appropriate
      residues/biomarkers may differ for various xenobiotics and even between species
      for the same xenobiotic. Further research is required to identify suitable
      markers that can be correlated with the occurrence and magnitude of ecologically
      important effects. Xenobiotics likely to have a direct effect on population
      dynamics are those that are persistent and adversely affect survival and
      reproduction. At present, this weak correlation is the only one that can be made
      between single-species laboratory tests and population effects.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8290738
TI  - Extracorporeal circulation for respiratory support in adults.

PMID- 8290739
TI  - Compensating occupational asthma.

PMID- 8290740
TI  - Pulmonary complications of bone marrow transplantation.

PMID- 8290741
TI  - Bambuterol: effective in nocturnal asthma.
AB  - Bambuterol was compared with placebo in 28 patients with nocturnal asthma in a
      randomized, double-blind cross-over study. All patients were symptomatic despite
      taking inhaled beta 2-agonists, inhaled corticosteroids (in 26 patients the
      median daily dose was 1500 micrograms) and oral corticosteroids (in eight
      patients the median daily dose was 10 mg). Patients demonstrated > or = 20%
      overnight fall in peak expiratory flow (PEF) for at least half of the 14-day run
      in period. They then entered two treatment periods lasting 14 days when
      bambuterol 20 mg nocte and placebo were given in random order. Compared to
      placebo, bambuterol produced a 16% improvement in mean PEF on waking (271 l min-1
      vs. 239 l min-1 P = 0.0002) and a 10% improvement in evening PEF measured 24 h
      after drug intake (318 l min-1 vs. 296 l min-1 P = 0.01). Bambuterol
      significantly reduced frequency of nocturnal awakening from 1.1 to 0.7 per night
      (P = 0.01) and nocturnal beta 2-agonist use from 2.7 to 2.1 puffs (P = 0.0004).
      Other nocturnal symptoms: cough, wheeze and dyspnoea were also significantly
      reduced during bambuterol treatment and patients quality of sleep was improved.
      The results indicate bambuterol (20 mg nocte) provides effective nocturnal
      bronchodilation with sustained effect for 24 h and may have a useful therapeutic
      role in the control of symptomatic nocturnal asthma.

PMID- 8290742
TI  - Regular three monthly oral ciprofloxacin in adult cystic fibrosis patients
      infected with Pseudomonas aeruginosa.
AB  - In 31 adult patients with cystic fibrosis (CF) who were chronically infected with
      Pseudomonas aeruginosa we examined the effect of giving regular three monthly
      oral ciprofloxacin. Patients received ciprofloxacin or placebo for 10 days every
      3 months for 1 yr in a randomized, double-blind, placebo-controlled study. During
      each course of treatment patients receiving ciprofloxacin reported an improvement
      in cough, sputum production and peak expiratory flow (PEF) P = < 0.005. During
      the year of study patients receiving ciprofloxacin showed an improvement in PEF
      when compared with those receiving placebo (P = < 0.05) but the changes in FEV1
      and FVC were not statistically different in either group. Regular oral
      ciprofloxacin was well tolerated but did not prevent hospital admissions or
      reduce the number of courses of intravenous antibiotics throughout the year. The
      median MIC to ciprofloxacin in the active treatment group rose from 0.5 mg l-1 to
      0.75 mg l-1 during treatment. We conclude that CF patients are likely to benefit
      from oral ciprofloxacin for exacerbations of respiratory symptoms. However,
      regular treatment with ciprofloxacin over 1 yr improves PEF but does not reduce
      the rate of hospital admissions with acute exacerbations of respiratory symptoms.

PMID- 8290743
TI  - Comparative bronchoalveolar concentrations of ciprofloxacin and lomefloxacin
      following oral administration.
AB  - In a comparative study, the concentrations of two fluoroquinolone antimicrobials,
      ciprofloxacin and lomefloxacin, were measured in serum, bronchial mucosal
      biopsies, epithelial lining fluid (ELF) and alveolar macrophages (AM). Thirty
      four subjects received either ciprofloxacin 250 mg b.d. (17 subjects) or
      lomefloxacin 400 mg o.d. for 4 days prior to sampling by bronchoscopic bronchial
      biopsy and bronchoalveolar lavage. Both ciprofloxacin and lomefloxacin showed
      favourable accumulation in the sites of infection with bronchial biopsy
      concentrations of 1.6 and 1.7 times those of serum respectively; ELF
      concentrations of 2.1 and 1.9 times serum; and AM concentrations of 11.8 and 20.1
      times serum respectively. The MIC90 for most of the common chest pathogens was
      reliably exceeded by both agents except for that of Streptococcus pneumoniae.

PMID- 8290744
TI  - The host inflammatory response prior to death in patients with cystic fibrosis
      and chronic Pseudomonas aeruginosa infection.
AB  - The intensity of the host inflammatory response to pulmonary infection with
      Pseudomonas aeruginosa immediately prior to death was determined in six patients
      with cystic fibrosis (CF). Plasma concentrations of neutrophil elastase alpha 1
      antiproteinase, tumour necrosis factor-alpha (TNF alpha) and serum C-reactive
      protein (CRP) were increased in the 7 days prior to death (P < 0.05) when
      compared with a period of clinical stability during the preceding 6 months. An
      increased inflammatory response was sustained for many weeks prior to death and
      was associated with poor symptom and lung function responses to apparently
      appropriate antibiotic treatment.

PMID- 8290745
TI  - Evaluation of fluticasone propionate (500 micrograms day-1) administered either
      as dry powder via a Diskhaler inhaler or pressurized inhaler and compared with
      beclomethasone dipropionate (1000 micrograms day-1) administered by pressurized
      inhaler.
AB  - Five hundred and eighty-five patients with moderate asthma, currently receiving
      400-1000 micrograms day-1 of an inhaled corticosteroid, were treated for 6 weeks
      in a double-blind, randomized, parallel group study with either 500 micrograms
      day-1 fluticasone propionate as a dry powder via a Diskhaler inhaler, 500
      micrograms day-1 fluticasone propionate via a pressurized inhaler or 1000
      micrograms day-1 beclomethasone dipropionate via a pressurized inhaler. For all
      three treatment groups, mean morning and evening peak expiratory flow rates
      (PEFRs) increased within 1 week of the start of treatment. There were also
      improvements in clinic lung function, daytime and night-time asthma symptoms and
      a reduction in daytime and night-time rescue bronchodilator medication in all
      three groups. There were no statistically significant differences between the two
      formulations of fluticasone propionate in any of the efficacy parameters.
      Fluticasone propionate via the Diskhaler was significantly more effective than
      beclomethasone dipropionate over the 6 week study period in reducing diurnal
      variation (mean difference--4 l min-1, 95% CI--8 to 0 l min-1: P = 0.03).
      Fluticasone propionate via the Diskhaler produced a statistically significant
      improvement in night-time symptoms when compared to beclomethasone dipropionate
      whereas, beclomethasone dipropionate 1000 micrograms day-1 was statistically
      significantly more effective than both formulations of fluticasone propionate in
      improving daytime symptoms (P < 0.05). However, these statistical differences
      must be viewed together with the fact that very few patients recorded a score of
      2 or more for both daytime or night-time symptoms. There was a similarly low
      incidence of adverse events with all three treatments with no evidence of
      hypothalamic pituitary adrenal (HPA)-axis suppression. The results of the 6-week
      comparative study showed that 500 micrograms day-1 fluticasone propionate whether
      administered via pressurized inhaler or Diskhaler is as effective and as safe as
      1000 micrograms day-1 beclomethasone dipropionate administered via a pressurized
      inhaler in the treatment of moderate asthma. Over 12 months fluticasone
      propionate 500 micrograms day-1 via a pressurized inhaler was at least as
      effective and as well tolerated as beclomethasone dipropionate 1000 micrograms
      day-1.

PMID- 8290746
TI  - Six months versus nine months chemotherapy for tuberculosis of lymph nodes: final
      results.
AB  - Of 199 patients treated for peripheral lymph node tuberculosis, 157 completed
      treatment as planned. Fifty received E2H9R9, 56 Z2 H9R9 and 51 Z2H6R6 regimens (E
      = Ethambutol; H = Isoniazid; R = Rifampicin; Z = pyrazinamide: numbers denote
      duration of therapy in months). In follow-up from 9 to 30 months, there were no
      significant differences between the regimens in enlargement of existing nodes,
      development of new glands or sinuses, in the need for new operative procedures,
      or in the percentage with measurable nodes at 30 months. Nine patients were felt
      to have had a clinical relapse (4 E2H9R9; 2 Z2H9R9; 3 Z2H6R6) although this was
      not confirmed bacteriologically in the five cases where material was sent for
      culture. These differences were not statistically different. The 6 month Z2H6R6
      regimen performs just as well as the 9 month regimens Z2H9R9 and E2H9R9 in
      patients with fully sensitive organisms, and has the additional benefits of
      convenience and reduced cost.

PMID- 8290747
TI  - Salmonella newport in the sputum of a patient with cystic fibrosis.

PMID- 8290748
TI  - Catastrophic deterioration in asthma induced by rifampicin in steroid-dependent
      asthma.

PMID- 8290749
TI  - Bilateral hilar enlargement with parenchymal homogenous density.

PMID- 8290750
TI  - Extrapulmonary effects of fenoterol compared to salbutamol in asthmatics.

PMID- 8290751
TI  - Respiratory arrests in young asthmatics on salmeterol.

PMID- 8290752
TI  - [Stroke units. Are they really beneficial?].

PMID- 8290753
TI  - [A four year study of therapeutical observation of patients with hypertension].
AB  - We attempt to quantify compliance with hypotension medication regimens in 620
      patients with hypertension at the Centros de Salud (community health centers) of
      Novelda and Elche (in the province of Alicante) and to assess the impact of a
      mixed-strategy health education program. The method used to evaluate compliance
      is the self-communicated interview as indicated by Haynes-Sackett. The
      intervention consisted of individualized instruction, family support, educational
      leaflets, and written instructions. Among the results obtained, we emphasize the
      following. First, 64% completed the treatment as prescribed, 16% stopped taking
      the medication, and 20% followed the regimen in a sporadic fashion, lack of
      motivation and forgetfulness being the main reasons cited for the latter. Second,
      27% of the patients with hypertension--among them, primarily young people and men
      -do not visit the center for monitoring. Third, the health education program is
      responsible for a significant increase in blood pressure measurements and in
      therapeutic compliance, also reducing the number of drop-outs. Fourth, 26% did
      not come to the unit at the end of the study period (four years) despite phone
      calls and house visits as reminders.

PMID- 8290754
TI  - [Cardiovascular risk factors in peripheral arterial disease. A study of 403
      cases].
AB  - We studied the prevalence of risk factors and related cardiovascular
      complications in 403 patients with periferal arterial disease (PAD) arising from
      atherosclerosis. The control group was made up of 126 patients of the same age
      and sex and without PAD. The average age was 66.9 +/- 12 years, and the
      percentage of men was 80%. Among the male subjects, smoking, the presence of
      diabetes, total cholesterol count, and age were the prevalent risk factors, even
      after logistic regression analysis. Among women, only smoking and diabetes showed
      significant differences. Among both sexes, the prevalence of arterial
      hypertension was similar to that of the controls. Greater prevalence of related
      cardiovascular complications was found only in men. We conclude that for PAD,
      smoking and diabetes are the most important cardiovascular risk factors, with
      total cholesterol level being an important additional factor in men.

PMID- 8290755
TI  - [Validity of four indirect methods which evaluate therapeutic compliance for
      arterial hypertension].
AB  - OBJECTIVES: To validate 4 indirect methods for detecting therapeutic non
      compliance in 157 patients in a community health center Centro de Salud "Carrus"
      in Elche, Alicante. MATERIALS AND METHODS: The methods employed are self related
      compliance (SC), therapeutic gains obtained, Morinsky-Green Test, and the level
      of knowledge of Batalla disease (LK). For verification purposes, pills were
      counted, allowing the formation of 2x2 tables to calculate indices of validity.
      The statistical analysis employed is the calculation of 95% confidence intervals.
      RESULTS: SC yields significantly the lowest sensitivity (13.7 +/- 7.9%) and the
      highest specificity (85.7% +/- 7.5%). The LK presents the highest sensitivity
      79.5 +/- 9.3%. SC underestimates non-compliance (32.5%) significantly, and the LK
      overestimates noncompliance (23.6%). CONCLUSIONS: The LK is a good method for
      detecting problems of low compliance and SC those of high compliance. It is
      recommended that both methods should be employed in a systematic fashion in
      clinical practice. However, the LK and SC cannot be used to calculate prevalences
      of therapeutic noncompliance in population-based studies.

PMID- 8290756
TI  - [Prevalence of arterial hypertension, proteinuria and hematuria in patients with
      simple renal cyst].
AB  - The simple renal cyst (SRC) is a common entity even though its actual incidence
      is difficult to determine given that it tends to manifest itself in an
      asymptomatic fashion. Occasionally, cases of SRC with clinical manifestations
      have been described in the literature, such as arterial hypertension (AHT) and
      biological alterations such as hematuria or proteinuria. The purpose of this
      article is to find the prevalence of AHT, proteinuria, and hematuria in patients
      with SRC detected via echography. 1,197 echographs that explored the renal area-
      a number equal to that of the number of patients--were reviewed. In 66% of the
      cases, the echographs were taken for some purpose unrelated to renal pathology.
      For those who presented SRC, blood pressure, proteinuria per 24 hours, and urine
      sediment were determined. SRC was detected in 93 patients (7.7%). The prevalence
      of AHT in patients with SRC was 31%, but 57% of those were older than 85 years.
      Two patients presented AHT and proteinuria; both fulfilled the criteria for
      nephrongiosclerosis. Two other patients presented hematuria and proteinuria; one
      was found to be afflicted with IgA nephropathy and the other with vesical
      carcinoma. A patient with hematuria was a carrier of renal lithiasis. We conclude
      that the prevalence of AHT in patients with SRC did not yield a significantly
      different result from that of the general population. In those patients who
      presented proteinuria and/or hematuria, one cause was found to be responsible;
      therefore, the presence of such alterations in patients with SRC should be
      considered coincidental.

PMID- 8290757
TI  - [Microbiological study via occluded telescopic catheter in patients under
      mechanical ventilation and suspected of pneumonia. Clinico-bacteriological follow
      up of the cases].
AB  - Pneumonias related to mechanical ventilation pose a serious diagnostic challenge
      and are responsible for elevated mortality. Conventional diagnostic methods are
      of little help. The introduction of invasive techniques such as bronchial catling
      via an occluded telescopic catheter (OTC) has proven to be an important advance
      in diagnosis and therapy. We have compared the bacteriological results obtained
      using OTC with those using conventional diagnostic methods such as
      tracheobronchial pumps (TBP) and hemocultures, and we have undertaken a
      bacteriological, clinical follow-up of the cases. Seventy-four patients under
      mechanical ventilation and suspected of pneumonia were under study. The study
      consisted to two consecutive phases of collecting bacteriological samples
      throughout the patient's evolution. A total of 121 fibrobronchoscopies were
      performed. The sensitivity obtained with OTC was 76%, and the specificity was
      100%. The two techniques, OTC and TBP, coincided in 38% of the cases. According
      to the bacteriological results obtained with OTC, the antibiotic treatment was
      modified in 44.5% of the patients. The sensitivity of the OTC was significantly
      less in those patients were the last doses of antibiotic was administered within
      two hours of performing the procedure. The procedure of gathering secretions from
      the inferior respiratory tract with OTC possesses greater sensitivity and
      diagnostic specificity in patients with mechanical ventilation and pulmonary
      infiltrates and improves the diagnosis performed by other conventional and
      routine techniques such as TBA and hemocultures.

PMID- 8290758
TI  - [Collagenous colitis].
AB  - We present in this article the cases of two women afflicted with aqueous chronic
      diarrhea with normal analysis, radiology, and endoscopy, but presenting sigmoid
      biopsy of collagenous colitis. One of them was treated with omeprazol and the
      other with corticoids. Despite not having found anomalies in the endoscopy, we
      recommend the practice of rectosigmoid biopsy in all cases of chronic diarrhea.

PMID- 8290759
TI  - [Amyloidosis and sleep-inhibiting apnea. A case improved by continuous positive
      pressure applied via the nose].
AB  - We present a patient with primary amyloidosis and sleep-inhibiting apnea and
      review the only two cases for which adequate references have been made in the
      medical literature. The importance of a complete anamnesis on the characteristics
      of sleep are stressed, and it is suggests that treatment with positive pressure
      applied via the nose (cPAP), as in the case presented here, can mean an important
      symptomatic improvement in a disease with an unfortunate prognosis.

PMID- 8290760
TI  - [Sleep deprivation and its effect on mood and performance of residents].

PMID- 8290761
TI  - [Stereotaxis surgery: therapeutic and diagnostic indications].

PMID- 8290762
TI  - [Ocular complications in AIDS patients].

PMID- 8290763
TI  - [Abdominal pain and fever in a 16 year-old male patient].

PMID- 8290764
TI  - [Myopia as the first manifestation of diabetes mellitus].

PMID- 8290765
TI  - [Cardiac tamponade as a form of presentation of Hodgkin's disease].

PMID- 8290766
TI  - [Vascular manifestations in Behcet's disease: a new case with femoral aneurysm].

PMID- 8290767
TI  - [Endocarditis caused by Actinobacillus actinomycetemcomitans on the bicuspid
      aortic valve].

PMID- 8290768
TI  - [The prognostic value of high-resolution electrocardiography in postmyocardial
      infarct patients].

PMID- 8290769
TI  - [Prevention and treatment protocols in thromboembolism].

PMID- 8290770
TI  - [A report on thrombolytic therapy in cardiology].

PMID- 8290771
TI  - [The activity registry of the Hemodynamics and Interventional Cardiology Section
      in 1992].

PMID- 8290772
TI  - [Registries in cardiology. An essential instrument in health planning].

PMID- 8290773
TI  - [An imaging and color echo-Doppler study of interventricular defects].
AB  - OBJECTIVE: Evaluation of ventricular septal defect with two-dimensional
      echocardiography and color flow Doppler. PATIENTS AND METHODS: We had studied by
      this method 180 patients; 97 males and 83 (mean age 1.5 +/- 1 years) diagnosed of
      a VSD. Cases with a complex cardiopathy were excluded from the study. The VSD was
      classified according to its location and relation to the tricuspid anulus and
      semilunar valves in perimembranous VSD, muscular VSD and subarterial double
      committed defect. The colour Doppler identified one or two areas of low through
      the ventricular septum with a zona of proximal acceleration throughout systole.
      Every group can be evaluated in different views but they all have a selective
      echocardiographic view except for muscular trabecular VSD. RESULTS: Seventy-six
      patients had perimembranous VSD (30 inlet, 26 trabecular and 20 infundibular
      outlet), 102 had muscular VSD (3 inlet, 97 trabecular and 2 infundibular-outlet)
      and 2 had a subarterial double committed defect. A ventricular septal aneurysm
      was associated in 20 patients with muscular or perimembranous defects. Six
      patients, 2 of the perimembranous trabecular VSD, 2 muscular-trabecular VSD and 2
      subarterial were initially misclassified. In this last 2 cases the turbulence
      created in the pulmonary valve was wrongly interpreted as pulmonary valvular
      stenosis; subcostal view for both tracts is necessary to avoid such mistake. In
      conclusion, color Doppler flow mapping is very useful to differentiate the
      various types as VSD and aids identification of multiples ventricular septal
      defects.

PMID- 8290774
TI  - [The prescription of physical exercise in the individual with aortic prostheses.
      The role of Doppler exercise study].
AB  - BACKGROUND AND OBJECTIVES: Exercise Doppler echocardiography allows measure
      valvular gradient during exercise, that could be useful in the prescription of
      physical activity in patients with a prosthetic aortic valve. METHODS: Exercise
      Doppler echocardiography was performed in 50 patients (mean age 53 +/- 12 years)
      with normally-functioning aortic prosthesis. Maximal exercise was performed by
      supine bicycle ergometry in 35 and modified Bruce protocol in 15. Continuous wave
      Doppler examinations were obtained at rest, during and at maximal exercise with a
      nonimaging transducer. RESULTS: The mean value of workload was 6.9 +/- 2 METS and
      there were no complications. Gradients at peak exercise were available in 43/50
      patients. Exercise induced a statistic significant increase in the heart rate (76
      +/- 14 to 136 +/- 26), systolic blood pressure (128 +/- 19 to 182 +/- 19 mmHg),
      peak gradient (29 +/- 9 to 61 +/- 17 mmHg) and mean gradient (16 +/- 5 to 32 +/-
      9 mmHg). The gradient was greater than 59 mmHg in 18/43 patients, greater than 69
      mmHg in 12/43 and greater than 79 mmHg in 5/43. CONCLUSIONS: Prescription of
      exercise in patients with aortic prosthesis requires perform an exercise Doppler
      echocardiography to measure the increase of valvular gradient with the exercise
      in each patient, since the stress testing could be normal, it can advise a rate
      of physical activity that determine very high prosthetic gradients.

PMID- 8290775
TI  - [Patients with an acute myocardial infarct treated in a coronary unit or in a
      general cardiology ward A comparative study].
AB  - INTRODUCTION AND OBJECTIVES: Coronary care units have been accepted as the
      standard location for treatment for patients with acute myocardial infarction.
      Nevertheless, controversy over their clinical impact, current role and cost
      effectiveness still remains. Due to the increased incidence of coronary artery
      disease in Spain, coronary care units are often full, and patients with acute
      myocardial infarction must be cared for in a general cardiology ward. METHODS: We
      have studied the features and results of 420 patients with acute myocardial
      infarction consecutively admitted to our hospital and compared patients cared for
      in the coronary care unit (329 [78%]) with those cared for in the cardiology ward
      (91 [22%]). Admission to cardiology ward or coronary care unit was based on the
      clinical judgment of emergency room physicians and the bed availability. No
      differences in age, sex, risks factors, prior history of coronary heart disease,
      blood pressure on admission, extension and complications of myocardial infarction
      were found between both groups. RESULTS: The percentage of patients with evolved
      and non-Q wave acute myocardial infarction, and admission electrocardiogram not
      suggestive of infarction was significantly higher in ward group (23 versus 2.4%,
      p < 0.001; 19 versus 11%, p < 0.01; and 43 versus 15%, p < 0.01; respectively).
      Although patients admitted to the coronary care unit underwent intravenous
      thrombolysis and coronary artery revascularization procedures in a higher
      proportion, mortality was similar in both groups (14% for ward patients and 17%
      for coronary care unit patients). When patients with evolved or non-Q wave
      infarctions and those with admission electrocardiograms not suggestive of
      infarction were excluded from the analysis, mortality rates remained similar.
      Subgroups mortality was in general similar for patients cared for in cardiology
      ward or in coronary care unit, although patients without shock, with Killip class
      I or II, and older than 70 years, had a slightly lesser mortality when treated in
      the Cardiology ward (5 versus 11%, 6 versus 11%, and 14 versus 28%,
      respectively). By contrast, patients with shock, Killip class III or IV, and
      electrocardiogram at admission not suggestive of infarction, had a lesser
      mortality when cared for in coronary care unit. CONCLUSIONS: We conclude that
      some subgroups of patients with acute myocardial infarction can be, if needed,
      effective and safely cared for in cardiology ward.

PMID- 8290776
TI  - [The treatment of acute myocardial infarct. Coronary units or general wards. The
      revival of an old controversy].

PMID- 8290777
TI  - [The predictors of success in the radiofrequency ablation of left accessory
      pathways using the single-catheter technic].
AB  - INTRODUCTION AND OBJECTIVES: To determine the predictors of successful
      radiofrequency current ablation of an accessory pathway using the single-catheter
      approach, we retrospectively analyzed 46 consecutive patients with left sided
      accessory atrioventricular pathways and manifest preexcitation. METHODS: Ablation
      using a single catheter advanced retrogradely towards the mitral valve was
      successful in 42 (91%). A radiofrequency pulse resulting in permanent accessory
      pathway block was defined as a successful pulse; a pulse that had no effect or
      caused only transient accessory pathway block was defined as an unsuccessful
      pulse. RESULTS: Successful radiofrequency pulses (n = 37) did not differ from
      those that failed (n = 56) in the local atrium-accessory pathway potential
      interval, in the accessory pathway-ventricle interval nor in the cumulative
      energy delivered. But in successful radiofrequency pulses, the amplitude ratio of
      local atrium and ventricular potentials tended to be larger (0.29 +/- 0.17 vs
      0.23 +/- 0.17; p = 0.053) and presumed accessory pathway potential was more often
      recorded (36 [97%] vs 38 [68%]; p = 0.006). The time elapsed from the beginning
      of the current application and the accessory pathway block was shorter in
      successful pulses as compared to those pulses producing only transient block (3.3
      +/- 2 s vs 6.9 +/- 4 s). CONCLUSIONS: The recording of a presumed accessory
      pathway potential, a large local A/V ratio and the occurrence of early conduction
      block in the accessory pathway were the best predictors of successful
      radiofrequency current application using the single-catheter approach.

PMID- 8290778
TI  - [Cardiac arrhythmias (XI). The surgery of ventricular arrhythmias in the decade
      of the nineties].

PMID- 8290779
TI  - [A cholesterol embolism during heparin treatment].
AB  - The cholesterol embolization is a rare complication of atherosclerosis. A direct
      implication of the treatment with anticoagulants in the etiology of the disease
      has been questioned, and now such therapy is considered more as an adjuvant
      factor with angiographic procedures than as a cause. A 60-year-old patient with
      an ischemic cardiomyopathy presented cholesterol embolization syndrome, confirmed
      by cutaneous biopsy histologic examination during treatment with heparin.
      Spontaneous evolution was favourable and only limited amputation of the lower
      limbs were required. The authors think that cholesterol emboli have a direct
      relationship to the treatment with heparin in this case, there being no other
      causes to justify its appearance.

PMID- 8290780
TI  - [Lipomatous hypertrophy of the interatrial septum simulating an atrial mass in a
      patient with a pulmonary embolism: its diagnosis by transesophageal
      echocardiography and percutaneous biopsy].
AB  - A case of lipomatous hypertrophy of the interatrial septum in a patient with a
      history of repeated pulmonary embolism is presented. Thickening of the
      interatrial septum mimicking the presence of a right atrial mass was evidenced by
      transthoracic and transesophageal echocardiography. Lipomatous hypertrophy was
      suspected. The diagnostic was confirmed by echo guided (transesophageal)
      percutaneous transvenous biopsy. To our knowledge, there is no relationship
      between lipomatous hypertrophy and pulmonary embolism and in this case, it could
      be associated with smoking habit and oral contraceptives.

PMID- 8290781
TI  - [The curative treatment of incessant atrioventricular tachycardia by
      radiofrequency ablation].
AB  - The permanent form of junctional reciprocating tachycardia is due to accessory
      pathways with retrograde long conduction times. We report the localization of the
      atrial insertion of the accessory pathway and successful ablation with
      radiofrequency in 3 patients. The participation of an accessory pathway in the
      tachycardia was demonstrated by atrial capture without changes in the sequence,
      with ventricular stimuli during His bundle refractoriness. The atrial insertion
      was localized by mapping near the os of the coronary sinus. In all cases one to
      three radiofrequency pulses applied at this point interrupted the tachycardia.
      Retrograde conduction through the accessory pathway reappeared in 30 min or
      earlier in all, with displacement of the point of earliest atrial activation, and
      tachycardia recurred. Total abolition of accessory pathway conduction and cure of
      the tachycardia required new radiofrequency applications, that in one case were
      done in a second procedure.

PMID- 8290782
TI  - [The trouts of the Thames].

PMID- 8290783
TI  - [The good health system. Results of a study (IV). A health system structure in
      central Italy. Relationship with its productivity].

PMID- 8290784
TI  - [Mondor's disease. Report of 22 cases].
AB  - Mondor's disease is a rare pathology which is characterized from a superficial
      thrombophlebitis more frequently of a vein on the anterolateral thoraco-abdominal
      wall. The world literature reported about 500 cases which have been compared to
      22 cases which represent our personal case-report. The most frequent etiological
      causes are represented by post-traumatic and infective events. The most important
      symptom is pain. The prognosis of the singol phlebitis focus is always
      favourable.

PMID- 8290785
TI  - [Correlations between membrane integrins and granulocyte defects in
      myelodysplastic syndromes].
AB  - The aim of the present study was to evaluate some functions of neutrophil
      granulocytes (PMNs), such as aggregation, superoxide production, chemotaxis and
      adhesion molecules involved in these processes, in 22 patients suffering from
      Myelodysplastic Syndrome (MDS), to clarify if granulocytes alterations described
      in this syndrome is really correlated with the expression of surface membrane
      integrins. Several patients suffering from MDS present granulocytopenia and/or
      absolute monocytoses; neutrophil granulocytes can have typical nuclear and
      cytoplasmatic alterations. These granulocytic anomalies are valuable in about 90%
      of patients suffering from MDS. The granulocytes showed a significant deficit in
      chemotaxis stimulated by serum activated with E. Coli, casein and formyl
      methionyl-leucylphenylalanine (fMLP) (p < 0.01) and in superoxide production
      stimulated by phorbol-myristate-acetate (PMA). We also studied the role of
      membrane integrin CD11/CD18 using specific monoclonal antibodies (MoAb). The
      cytofluorimetric analysis demonstrated a significant inhibition in expression of
      CD11b/CD18 receptors in patients suffering from MDS (p < 0.001), while the
      expression of CD11a/CD18 and CD11c/CD18 receptors was normal. In conclusion we
      found specific alterations in PMNs functions in MDS and a correlation of these
      anomalies with membrane integrins of PMNs is therefore possible.

PMID- 8290786
TI  - [Gastric localization of sarcoidosis].
AB  - Sarcoidosis is a systemic granulomatous disease of unknown etiology,
      characterized by an immunological disorder with accumulation of activated
      lymphocytes and macrophages in all the organs and apparatus. The intrathoracic
      lymphnodes and the lung remain the most common sites of such disease. The
      gastrointestinal sarcoidosis, particularly of the stomach, is very rare. The
      stomach may be the primitive or the secondary (systemic sarcoidosis) site of
      sarcoid granuloma. The endoscopic aspects of the gastric mucosa are variable:
      localized or diffused hyperemia, single or multiple ulcers, aspects of atrophic
      gastritis with easy bleeding during contact, rigid mucosa and so on. Generally
      asymptomatic, the disease may show symptoms as pain in the epigastrium, nausea,
      vomiting, haematemesis and so on. The wide range of gastric pathologies
      resembling sarcoidosis both on a histological level and on a clinic-endoscopical
      one (syphilis, histoplasmosis, Crohn's disease, stomach cancer) require an
      extremely accurate diagnosis above all for the setting out of the therapy with
      steroids which are the most appropriate drugs (prednisone). Three out of thirty
      two patients observed for respiratory problems, already affected by cutaneous and
      pulmonary sarcoidosis, started suffering from gastric symptoms of different kind:
      pain in the epigastrium, haematemesis, weight loss, nausea and post-prandial
      vomiting. Gastroscopy and biopsy, with histopathologic examination of gastric
      mucosal specimens taken from the most suspicious sites, confirmed the diagnosis
      of sarcoidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290787
TI  - [Therapeutic use of thymostimulin in HIV-seropositive subjects and with
      lymphadenopathy syndrome].
AB  - The Authors have carried out a study on the therapeutic effect of thymostimulin
      in HIV-positive subjects with lymphoadenopathy syndrome. Of the 140 selected
      patients, 70 were subjected to a treatment with thymostimulin (50 mg/die i.m. for
      30 days + 50 mg/3 times a week i.m. in the second, third and fourth month + 50
      mg/once a week i.m. in the fifth and sixth month) and of these patients, 60
      completed the treatment and the estimated follow-up of twelve months. At the end
      of this period the following observations were made about the group treated: 1)
      improvement of the skin reaction to the Multitest (CMI) antigens in 66.7% of the
      cases, no changes in 30% of the cases and deterioration in 3.3% of the cases; 2)
      the total T-lymphocytes show an increase in the 6th month, remaining stable for
      the check-ups of the 9th and 12th months; 3) a significant increase of the CD4
      lymphocytes in the 6th month with CD4/CD8 ratio close to the normal values,
      remaining the same even at the end of the follow-up; 4) during the study none of
      the treated patients developed opportunistic infections or HIV-related neoplasms.
      The results were also subjected by the Authors to statistical analyses between
      the two groups and therefore testify to a favourable effect of thymostimulin with
      an improvement in the laboratory indications taken into consideration and, above
      all, the quality of life.

PMID- 8290788
TI  - [Heart sarcoidosis. A case of mitral and ascending aorta involvement].
AB  - We describe a case of cardiac sarcoidosis manifested by arrhythmias, shock, chest
      pain, mitral valve prolapse and incompetence, aortic vascular involvement.
      Steroid therapy corrected shock and arrhythmias, but was unable to prevent the
      progression of the mitral valve insufficiency. Subsequently pulmonary and
      tricuspid valve incompetence were also observed.

PMID- 8290789
TI  - [Neuropathy or the brachial plexus associated with pregnancy. Report of a case].
AB  - Idiopathic neuropathy of the brachial plexus can appear in two different forms, a
      sporadic one and a family one, autosomic dominant, much rarer which can be
      associated with pregnancy. Authors report a clinical case of brachial plexus
      neuropathy in a patient to the seventh month of pregnancy and with no observation
      of hereditary disease of nervous peripheric system. Clinical,
      electrophysiological aspects and possible pathogenetic mechanisms are here
      debated. Also therapeutic strategies and psychological implications are
      considered.

PMID- 8290790
TI  - [Acute renal failure with fast resolution in cocaine addict].

PMID- 8290791
TI  - [Autoimmunity and HCV].
AB  - Since the discovery of HCV in 1989 and the availability of reliable tests to
      detect HCV infection, we are aware that a number of chronic hepatitis cases,
      previously considered as autoimmune, are closely related to HCV. This applies
      particularly to adults with autoimmune hepatitis type 2 (LKM1 positive): in the
      Mediterranean area the vast majority of such cases are indeed anti-HCV/HCV RNA
      positive. Different is the case of pediatric type 2 autoimmune hepatitis
      patients, whose disease is HCV-free and remains still "primary". In autoimmune
      hepatitis type 1 (anti-nuclear and anti-action antibody positive) HCV infection
      seems to be confined to patient with mild-moderate disease activity, while most
      of the severe cases are consistently HCV-free. Autoantibody testing is relevant
      in detecting autoimmune hepatitis within the cryptogenic subgroup and prior to
      interferon treatment of HCV-related chronic hepatitis.

PMID- 8290792
TI  - [Coronary angioplasty. Indications, diagnostic and indicative methods, follow-up
      results].
AB  - Coronary angioplasty (PTCA) represents a valid alternative to coronary artery
      bypass surgery (CABG) in several cases; moreover, PTCA might be performed, for
      myocardial revascularization, even in patients in whom CABG is transitory or
      definitely contraindicated. However, the guidelines for mechanical myocardial
      revascularization are still mainly based on clinical criteria and the only
      angiographic data should not be sufficient to extend the indications for PTCA.
      Despite the technical improvement of the procedure and the material used, PTCA
      continues to have two main limitations: the relatively high acute complications
      rate (4-7%) and long-term restenosis rate (20-40%). The advent of new techniques
      for myocardial revascularizations (transluminal atherectomy, coronary stents,
      laser angioplasty) might partially reduce these limitations.

PMID- 8290793
TI  - [Orphan diseases].
AB  - Basic investigation in industrial laboratories are mainly addressed to widespread
      diseases. It follows that: 1) basic research is addressed chiefly to the well
      known and largely diffuse diseases; 2) rare diseases are not usually studied and
      therefore little chance is given to their physiopathological or therapeutic
      knowledge. Hence the name of orphan diseases. The aim of this study is to
      contribute to the stimulation of innovative and applied basic research of orphan
      diseases and therefore to gradually confine the number of incurable rare
      diseases. Our proposal upsets the studies undertaken in some foreign countries
      and Italy on the orphan drugs (e.g. Orphan Drug Act, issued in the USA in 1982)
      since we suggest starting from a study on disease more than studies on drug. The
      planning of studies of disease may be undertaken on various points of view
      (prevalence, clinical features, prognosis, social cost, etc.), while this may be
      very hard for the drug. Therefore we suggest starting from a study plane,
      classification and estimation of rare diseases, shared for apparatus. These
      studies may be undertaken on a vigorous rationale (more than studies on orphan
      drugs) and therefore they may bring about to the definition of a national
      (government) planning for addressing consistent financial resources to the study
      of pathophysiology and therapy (or prevention) of the major orphan diseases.
      Adequate studies within the European Community may be planned in the near future,
      since most rare diseases are presumed to have a common distribution within the
      Community.

PMID- 8290794
TI  - [Anaerobic bacteria and gynecologic infections].
AB  - The normal vaginal flora consists of a wide variety of bacteria and the
      composition of this microflora is influenced by hormonal, metabolic and
      pharmacological factors. An increased concentration of a mixed anaerobic flora
      (Mobiluncus, Prevotellae, Peptostreptococci and Gardnerella vaginalis) appears to
      be an early stage in the development of bacterial vaginosis or in the infection
      of the upper genital tract. Women with bacterial vaginosis are at increased risk
      of bartholinitis, skenitis, pelvic inflammatory disease, postpartum and
      postabortal endometritis, chorioamnionitis and infections following gynecologic
      surgery or diagnostic procedure.

PMID- 8290795
TI  - Salivary immunoglobulin A production in chronic bronchitis patients given an
      orally administered bacterial extract.
AB  - The concentration of secretory immunoglobulin A (IgA) has been measured by the
      immunodiffusion method in 28 chronic bronchitis patients (group A) and in 11
      comparable patients receiving corticosteroid therapy (0.5 mg/kg/day prednisone;
      group B). The measurements have been taken before and after oral administration
      of Broncho-Vaxom which is an extract of bacteria that usually cause infection of
      the respiratory tract. The mean concentration of secretory IgA in the saliva was
      increased by over 130% after the 10-day administration of the preparation to
      group A patients. This increase was statistically significant between the 12th
      and 40th day after the beginning of the treatment (p < 0.001). It fell to initial
      levels after 1 month in 15 patients (group A2) who received a single treatment
      course. In 13 patients (group A1) who received a second treatment course,
      beginning 1 month after termination of the first course, the high concentration
      of IgA in saliva persisted for at least 3 months. The saliva IgA was increased by
      over 35% in 11 chronic bronchitis patients (group B) who received corticosteroid
      therapy. In this group of patients the rise of IgA levels began later than in
      group A. The IgA fell to initial level after 1 month in 5 patients (group B2) who
      received a single treatment course. In 6 patients (group B1) who received a
      second treatment course the high concentration persisted longer. The saliva level
      of IgA in groups A and A1 was higher than in groups B and B1 (p < 0.05 and p <
      0.001, respectively). No differences of IgA in the saliva between groups A2 and
      B2 were found during the study.

PMID- 8290796
TI  - Nocturnal oxygen saturation and sleep quality in long-term survivors of
      thoracoplasty.
AB  - The extent and the predictors of nocturnal hypoxemia were studied in 9 men and 11
      women treated for pulmonary tuberculosis by thoracoplasty 30-54 years previously.
      The patients had a scoliotic (Cobb) angle of 4-53 degrees. Median values for
      pulmonary function were: forced expiratory volume in 1 s 1.2 liters (49% of the
      predicted value), vital capacity 1.9 liters (54%), total lung capacity 3.6 liters
      (62%), and supine waking partial pressure for arterial oxygen 9.7 kPa. Four
      patients were hypercapnic. The patients' mean nocturnal SaO2 ranged from 83 to
      94% (median 91.8%), and the SaO2 level below which the patients spent 10% of the
      total nocturnal recording time ranged from 78 to 92% (median 89.4%). A multiple
      stepwise linear regression analysis identified supine waking SaO2 as a
      significant predictor of nocturnal O2 desaturation, accounting for about 80% of
      the variability in nocturnal SaO2 levels; lung function values and Cobb angle
      were not significant independent predictors. The sleep quality, assessed by EEG,
      was good. It is concluded that in thoracoplasty patients with mild hypoxemia
      during wakefulness, the degree of sleep-related oxygen desaturation was modest
      and closely related to the waking level of SaO2.

PMID- 8290797
TI  - Prevalence of sleep apnea among Japanese industrial workers determined by a
      portable sleep monitoring system.
AB  - We developed a new portable sleep monitoring system and studied the prevalence of
      sleep apnea syndrome among Japanese industrial workers. This device assessed
      three kinds of parameters: nasal airflow, tracheal sound and electrocardiogram
      (ECG), and digitally stored the clock time of the onset of apnea, apnea duration
      and R-R intervals by a built-in microcomputer. After monitoring, the portable
      sleep monitor was connected to a host computer, and apneic episodes, the so
      called 'apnea index' as apneic episodes corrected by measuring time ('AI') and R
      R intervals were analyzed. In 170 inpatients referred to our sleep clinic, sleep
      monitoring by this device was performed simultaneously with all-night
      polysomnography, and the sensitivity and specificity of this device was
      determined under different criteria of the apnea index (AI) (AI > 5, 10, 15 and
      20 episodes/h) by polysomnography. In all AI criteria, the sensitivity was more
      than 90%, and the specificity was also reasonably high. Using this system,
      successive 2-night home sleep monitoring was performed on 168 healthy workers in
      one Japanese industrial company, and 159 people (140 males; 19 females) who had
      successful monitoring were analyzed. The percentage of persons who had 'AI' of
      more than 10 episodes/h was 7.5%. There were no significant correlations between
      'AI' and age, body weight or scores estimated by sleep questionnaires. These
      results suggest that even in people who are seemingly healthy significant apneic
      episodes could be detected by the portable home sleep monitoring system. This
      system may therefore be useful in evaluating the occurrence of sleep apnea
      syndrome in general populations.

PMID- 8290798
TI  - Renal sodium excretory function during acute oxygen administration.
AB  - To evaluate the effect of O2 administration and O2 removal on renal Na+
      excretion, 12 hypoxemic eucapnic patients affected by chronic obstructive
      pulmonary disease (COPD) and 9 normal subjects were studied. After 1 h in the
      supine position, O2 was administered for 3 h by a tight-fitting face-mask. Urine
      and blood samples for renal Na+ excretion evaluation were taken at times 0, 60
      and 180 min. After O2 removal both the blood and the urine samples were taken
      again for a further 3 h. In normal subjects, urinary Na+ excretion did not vary
      after both O2 administration and removal. On the contrary, in patients affected
      by COPD renal Na+ excretion significantly increased during O2 administration
      (from basal values of 0.08 +/- 0.01 to 0.17 +/- 0.02 mEq/min at 180 min, p <
      0.05), and returned to baseline levels (0.13 +/- 0.03 mEq/min) after 3 h from O2
      removal. The basal fractional excretion of filtered Na+ was significant lower in
      hypoxemic patients than in normal subjects (0.72 +/- 0.3% in patients with COPD
      vs. 0.95 +/- 0.7% in normal subjects, p < 0.05), while, at the end of O2
      administration, it became higher in patients with COPD than in controls (1.62 +/-
      0.4% in patients with COPD vs. 0.89 +/- 0.5 in control subjects, p < 0.001). In
      conclusion, our findings showed an oxygen-related increase of both the urinary
      Na+ excretion and the fractional excretion of filtered sodium in patients
      affected by COPD.

PMID- 8290799
TI  - A new aerosol device for bronchial provocation tests.
AB  - A special new device for diagnostic (bronchoprovocation) and therapeutic aerosol
      application is described. It consists of a high quality nebulizer system combined
      with a 10-liter storage bag which serves as an aerosol 'conditioner' (saturated
      ambient temperature and pressure conditions) and as a holding chamber to increase
      the respirable aerosol fraction and hence pulmonary deposition (Pari Provocation
      Test I). It allows ten times better standardized pulmonary aerosol deposition
      compared with the generally used nebulizers for calculation of dose-response
      curves especially for asthma provocation and dilatation tests. If slow
      inspiratory vital capacity maneuvers are used, pulmonary deposition of about 100
      mg aerosol is achieved in children and adults. This device is especially
      important when exact dosing (also for therapeutic reasons) is required in the
      expanding field of topical and systemic aerosol application to or via the lung.

PMID- 8290800
TI  - Contraction of bovine isolated bronchial airways: effects of epithelium removal.
AB  - The influence of the epithelium on the contractile responses of bovine bronchial
      rings to acetylcholine, carbachol, 5-hydroxytryptamine and histamine was studied.
      Epithelium removal caused a significant leftward shift of the acetylcholine
      concentration-effect curve, pD2 values were 2.86 +/- 0.11 and 3.34 +/- 0.18 for
      intact and rubbed tissue, respectively (P < 0.05). However, there was no change
      in the acetylcholine maximal response. The sensitivity and responsiveness of the
      bovine bronchus to the other spasmogens were not significantly altered by removal
      of the epithelium. These results suggest that the epithelium of bovine bronchi
      modulates only acetylcholine-induced contraction.

PMID- 8290801
TI  - Pulmonary emphysema followed by pulmonary fibrosis of undetermined cause.
AB  - Idiopathic pulmonary fibrosis (IPF) and pulmonary emphysema (PE) have distinct
      clinical and pathological characteristics, and have been considered to be
      separate disorders. However, recent animal experiments have suggested that, with
      regard to their pathogenesis, the diseases have some features in common. However,
      there are no clinical data supporting this hypothesis. We report here 9 patients
      (all male, 67 +/- 2 years, mean +/- SE) who had PE followed by IPF. They were
      found among 152 PE patients who came to Tohoku University Hospital during the
      past 15 years (1976-1991). All patients were male and heavy smokers and 2
      patients also had prostate cancer and gastric cancer, respectively. Three
      patients were alive during this study and had been diagnosed as having IPF and PE
      by the combination of transbronchial biopsy, selective alveolobronchogram, CT
      examination and lung function tests. The diagnosis of IPF and PE in the other
      patients was based on the pathological findings of autopsied lungs in addition to
      clinical findings. All patients showed PE mainly in the upper lobes and IPF in
      the lower lobes. In all patients, in addition to all known causes of pulmonary
      fibrosis, the possibilities that chronic or recurrent infections in PE induced
      pulmonary fibrosis and that IPF produced emphysematous changes were carefully
      excluded by medical records and pathological findings. It is not clear whether
      the occurrence of emphysema and pulmonary fibrosis in these cases is
      coincidental, or whether the two diseases are linked by a common pathogenetic
      pathway.

PMID- 8290802
TI  - Early squamous lung cancer and longer survival rates.
AB  - The criteria for early squamous lung cancer remain open to discussion as patients
      who have been treated for early stage lung cancer, such as T1N0M0, and appear to
      have been cured clinically may die from recurrent or metastatic tumors. We
      reviewed the pathological data on 242 surgical patients with squamous lung cancer
      and found 31 cases (13%) of early lung cancer, included were early lung cancer of
      the hilar type as a lesion restricted to the bronchial wall without lymph node
      involvement, and early lung cancer of the peripheral type as a lesion of less
      than 2 cm and surrounded by visceral pleura but without lymph node involvement.
      Of 89 patients with hilar-type squamous lung cancer, 17 (19%) had early lung
      cancer, and 14 (9%) of 153 patients with peripheral-type squamous lung cancer had
      early lung cancer (p < 0.05). For early lung cancer of the hilar type, all but 1
      (94%) were detected using sputum cytologic study and bronchoscopy. For early lung
      cancer of the peripheral type, all were detected on chest X-ray, but 57% were
      cytologically proven to be malignant. The 5-year survival rate for patients with
      early lung cancer, according to this new criteria is 90%; 92% for the hilar type
      and 88% for the peripheral type. Thus, classification of early squamous lung
      cancer is pertinent for determining the prognosis and selection of treatment. We
      emphasize that efforts be made to detect early lung cancer.

PMID- 8290803
TI  - Quinacrine-induced pleural inflammation in malignant pleurisy: relation between
      drainage time of pleural fluid and local interleukin-1 beta levels.
AB  - In this study, the levels of interleukin-1 beta (IL-1 beta) were measured in
      pleural fluid from patients with chronic malignant pleural effusions, before and
      during quinacrine-induced pleurodesis. IL-1 beta levels increased significantly
      within 24 h after the instillation of quinacrine (p < 0.001). The levels of IL-1
      beta correlated with the amount of pleural fluid production as well as with the
      tube drainage treatment time. Thus, the more IL-1 beta levels increased the
      higher pleural fluid production was seen and a longer drainage treatment time was
      needed. There were no correlations between IL-1 beta levels and degree of fever,
      recruitment of pleural leucocytes, activity of pleural coagulation or inhibition
      of pleural fibrinolysis.

PMID- 8290804
TI  - Encapsulated type II pneumocyte adenoma: a case report and review of the
      literature.
AB  - An unusual benign lung neoplasm, a papillary adenoma of type II pneumocytes, was
      resected from a 26-year-old man who showed no clinical symptoms. The tumor was
      2.0 cm in diameter and was localized in the subpleural region of S7 of the right
      lung; the cut surface showed a spherical medullary mass encapsulated by a thin
      layer of connective tissue. Histologically, there were cuboidal to columnar
      epithelial cells with a little nuclear atypia showing a monotonous papillary
      pattern with a delicate stroma in most parts of the tumor. There was neither
      capsular invasion nor metastasis of tumor cells. Nuclear DNA analysis of the
      tumor cells showed a diploid pattern and a low S-phase fraction. The
      immunohistochemical study revealed that most tumor cells contained a large amount
      of surfactant apoprotein in the cytoplasm. Osmiophilic lamellar bodies
      characteristic of type II pneumocytes were frequently found by electron
      microscopy. These findings indicate that this was a benign adenoma of the lung
      arising from type II pneumocytes.

PMID- 8290805
TI  - Does prehospital care by physicians result in a better outcome than resuscitation
      by other EMS personnel?

PMID- 8290806
TI  - The pathophysiology of sudden death in atherosclerotic heart disease.

PMID- 8290807
TI  - Active compression-decompression resuscitation: effects on pulmonary ventilation.
AB  - This investigation was designed to test the hypothesis that active compression
      decompression resuscitation is able to independently provide improved levels of
      minute ventilation when compared to high-impulse manual cardiopulmonary
      resuscitation (CPR). Eight adult beagles (10-15 kg) were studied after induction
      of ventricular fibrillation. Single 1-min CPR trials were performed while
      arterial blood gases and minute ventilation were monitored. ACD and high-impulse
      CPR were performed sequentially, in random order at compression rates of 120/min,
      1.5- to 2.0-inch compression depth and 50% duty cycle. Minute ventilation
      averaged 3.6 +/- 0.77 1 during high-impulse CPR and increased to 4.9 +/- 0.88 1
      during ACD CPR. No difference was observed in arterial blood pH, PCO2, or PO2
      when ACD was compared to high-impulse CPR. We conclude that ACD CPR provides
      improved levels of minute ventilation when compared to high-impulse manual CPR in
      this canine model of cardiac arrest. Improved minute ventilation may contribute
      to the mechanism of improved cardiopulmonary hemodynamics reported in previous
      investigations of ACD CPR. Further investigation is warranted to determine the
      effects of ACD CPR on pulmonary ventilation in human subjects after cardiac
      arrest.

PMID- 8290808
TI  - End-tidal CO2 and plasma lactate level: a comparison of their use as parameters
      for evaluating successful CPR.
AB  - Serial changes of end-tidal CO2 (ETCO2) and plasma lactate levels during CPR have
      been described as useful to investigate or evaluate the results of CPR. However,
      there have been no reports comparing these parameters in the same model. By
      inducing cardiopulmonary arrest (2-7 min) in 28 Wistar rats, ETCO2 and serum
      lactate levels were studied after and just before CPR, respectively. In the
      survived group (N = 16), ETCO2 was maintained in high levels (20.1-16.3 mmHg),
      however in the non-survived group (N = 12), ETCO2 showed an abrupt decline (6.0
      2.0 mmHg). The lactate levels before CPR in two groups were significantly higher
      than those of control levels, however there was no significant difference just
      before the CPR between the two groups. ETCO2 during CPR is a useful indicator for
      determining the successful application of CPR. However, serum lactate levels
      sampled just before the onset of CPR did not prove to be a useful indicator of
      successful CPR in rats.

PMID- 8290809
TI  - Thyroid hormone loss and replacement during resuscitation from cardiac arrest in
      dogs.
AB  - Circulating concentrations of thyroxine (T4), triiodothyronine (T3), and reverse
      triiodothyronine (rT3) were followed in dogs subjected to 9 min of normothermic
      ventricular fibrillation. Significant decreases were detected 12 h post-arrest
      when compared to pre-arrest levels in total T4 (P < 0.0005), free T4 (P <
      0.0005), total T3 (P < 0.003), and free T3 (P < 0.003), and levels of reverse T3
      were significantly elevated (P = 0.0001). Similar changes occurred with only 30 s
      of arrest. Post-arrest replacement therapy with 7.5 micrograms/kg per h (Rx-7.5)
      and 15 micrograms/kg per h (Rx-15) levothyroxine sodium (L-T4) increased total
      T4, free T4, and total T3 (P < 0.01). Free T3 decreased in the Rx-7.5 group (P <
      0.01) and did not fall in the Rx-15 group (P = 0.16). Reverse T3 increased with
      either treatment (P < 0.005). Both treatment groups had higher levels of all five
      hormones than non-treated animals (P < 0.001). Neurologic function, assessed with
      a standardized scoring system, showed significant improvement in the treated
      groups by 6 h (P < 0.05, compared to non-treated group) and remained significant
      through 24 h post-arrest (P < 0.05). The documentation of rapid and dramatic
      changes in thyroid hormones immediately following cardiac arrest and
      resuscitation indicates a significant acute hypothyroid state that may
      potentially benefit from replacement therapy.

PMID- 8290810
TI  - Comparative assessment of the ventricular fibrillation detection algorithms in
      five semi-automatic or advisory defibrillators.
AB  - The sensitivity and specificity of ventricular fibrillation (VF) detection in
      three semi-automatic defibrillators (Laerdal Heartstart 3000, Spacelabs First
      Medic 610, Physio-Control Lifepak 300) and two advisory defibrillators (S&W
      DMS940, Marquette Responder 1500) were assessed with 25 ECG recordings, each of
      length 40 s. Of the 25 ECG recordings, 12 contained VF requiring defibrillation,
      three contained a tachyarrhythmia with a waveform similar to VF but which self
      terminated, and 10 were selected from abnormal rhythms and artefacts which
      contained some features similar to VF. Sensitivity was assessed from the VF data.
      Specificity was assessed from both the rhythm preceding VF or the
      tachyarrhythmias, and from the VF-like data. The response to a changing rhythm
      was assessed from the self-terminating tachyarrhythmias. Each recording was
      replayed to the defibrillators at three signal amplitudes (normal, half and
      double). For each defibrillator, requests to check the patient and advice to
      shock were noted separately. The sensitivity for recommending a shock when a
      shock was required varied from 81 to 97%. The sensitivity for drawing attention
      to VF, either through requesting the patient to be checked or advising a shock,
      varied from 92% to 100%. There were no false detections in the rhythms preceding
      VF or the tachyarrhythmias (specificity with good quality signals 100%). The
      specificity with the VF-like data ranged from 63 to 90% for recommending a shock,
      and from 63% to 70% for requesting the patient be checked or shocked. There was
      no difference between the defibrillators for VF detection, but there was a
      significant difference between the semi-automatic and advisory defibrillators (P
      < 0.05) for the specificity of the final recommendation.

PMID- 8290811
TI  - A new method of two-resuscitator CPR.
AB  - Standard two-resuscitator cardiopulmonary resuscitation (CPR) (one resuscitator
      providing Bag Valve Mask (BVM) ventilation and one chest compressions) was
      compared with a modified method where one resuscitator held the mask while the
      second provided ventilation and compressions. Twenty-two subjects used both
      methods in random order on a recording manikin equipped to measure minute volume
      (Vm), tidal volume (Vt), respiratory rate (RR), compression rate (CR) and depth.
      Vm and Vt were greater with modified CPR, but the CR was slower. Percent of
      compressions < 38 mm, 38-51 mm or > 51 mm did not differ between techniques
      ((Modified--VM, 12.6 1 (S.D. 2.5); Vt, 1110 ml (S.D. 116); CR, 57 (S.D. 11), < 38
      mm 6% (S.D. 14), 38-51 mm 36% (S.D. 33), > 51 mm 58% (S.D. 41); Standard--Vm, 9.7
      1 (S.D. 3.8); Vt, 640 ml (S.D. 230); CR, 75 (10), < 38 mm 9% (S.D. 22), 38-51 mm
      52% (S.D. 37), > 51 mm 38% (S.D. 38)). Modified CPR greatly improves ventilation
      but reduces CR.

PMID- 8290812
TI  - Unexplained pneumoperitoneum in association with basic cardiopulmonary
      resuscitation efforts.
AB  - During the mouth to mouth ventilation of basic life support, the high inflation
      pressures generated may result in later complications. Pulmonary barotrauma may
      result in pneumothorax or pneumomediastinum, and high pressures applied to the
      gastrointestinal tract may lead to gastric rupture and pneumoperitoneum. A case
      is reported of pneumoperitoneum in the absence of pneumothorax, pneumomediastinum
      or gastrointestinal perforation and the literature relating to this unusual
      condition is reviewed.

PMID- 8290813
TI  - Effects of induced hypothermia in patients with septic adult respiratory distress
      syndrome.
AB  - OBJECTIVE: To test the hypothesis that treatment with hypothermia affects the
      course of overwhelming acute respiratory failure associated with sepsis. DESIGN:
      Concurrent-controlled, prospective study. SETTING: Adult multidisciplinary ICU in
      a teaching hospital. PATIENTS: Nineteen consecutive patients with septic ARDS
      mechanically ventilated and a P(A-a)O2 > 500 Torr during 36 h on > or = 10 cm H2O
      of PEEP. INTERVENTIONS: Patients were assigned to receive conventional treatment
      (n = 10) or conventional treatment plus mild hypothermia (32-35 degrees C)
      instituted as a last resort (n = 9). RESULTS: Hypothermia (33.7 +/- 0.6 degrees
      C) was associated with a reduction in mortality rate (67% vs. 100%, P < 0.05),
      P(A-a)O2 (P < 0.001), heart rate (P < 0.001), cardiac index (P < 0.01), and QS/QT
      (P < 0.01). There were no significant differences in oxygen consumption (VO2)
      before (243 +/- 74 ml/min) and during treatment with hypothermia (246 +/- 87
      ml/min) although O2 extraction increased during hypothermia (26 +/- 6 vs. 30 +/-
      6%, P < 0.05). CONCLUSIONS: This study suggests that hypothermia was effective in
      improving oxygenation and survival in patients with severe ARDS associated with
      sepsis, even though VO2 was unchanged.

PMID- 8290814
TI  - An evaluation of a short course in resuscitation training in a district general
      hospital.
AB  - One hundred nurses underwent a short form of cardiopulmonary resuscitation
      training, comprising a short lecture and practical training. This significantly
      improved theoretical knowledge, but failed to achieve a uniformly high standard
      of practical skill. After initial training the subjects were divided into three
      groups. Group 1 underwent monthly refresher sessions, Group 2 a single refresher
      at 3 months and Group 3 no refresher training prior to re-testing of all subjects
      at 6 months. Knowledge and skills had declined in all three groups. Theoretical
      scores were better preserved in the groups having refresher training. Frequent
      refresher training failed to improve the poor initial performance in the
      practical skills. The time required to produce adequate training is greater than
      that which can be provided by clinical staff and necessitates the appointment of
      a resuscitation training officer.

PMID- 8290815
TI  - Angiotensin II improves myocardial blood flow in cardiac arrest.
AB  - Epinephrine is used to increase coronary perfusion pressure and improve
      myocardial blood flow during cardiac arrest. Alternative vasopressors may have
      hemodynamic advantages over epinephrine. The purpose of this investigation was to
      test the effect of the vasopressor angiotensin II on myocardial blood flow in a
      swine model of cardiac arrest. Eleven swine were anesthetized and instrumented
      for regional blood flows by radiolabeled microsphere technique. A baseline blood
      flow measurement (BFM), coronary sinus and aortic blood gases were obtained in
      normal sinus rhythm (NSR). Ventricular fibrillation (VF) was induced and
      mechanical CPR begun after 10 min of VF. A BFM and blood gases were obtained
      during CPR. Angiotensin II, 50 micrograms/kg, was administered at 13 min of VF. A
      repeat BFM and blood gases were obtained following angiotensin II. Defibrillation
      was attempted at 16.5 min of VF. If return of spontaneous circulation (ROSC)
      occurred a fourth BFM and blood gases were obtained. Myocardial blood flow was
      134.2 +/- 40.1 ml/100 g per min during NSR. This fell to 15.1 +/- 19.9 with CPR
      alone, and rose to 66.9 +/- 69.8 following angiotensin II administration (P =
      0.04; by two tailed T-test). Myocardial blood flow following ROSC further
      increased to 212.6 +/- 58.0. Angiotensin II in a dose of 50 micrograms/kg
      significantly increases myocardial blood flow in this model of cardiac arrest.

PMID- 8290816
TI  - The no-reflow phenomenon and CPR.

PMID- 8290817
TI  - Descriptive epidemiology of genitourinary cancers.
AB  - The American Cancer Society estimates that, in 1993, genitourinary (GU) cancers
      will account for about 37% of all new cases of cancer in men and about 4% in
      women. Approximately 18% of all cancer deaths in men and 3% in women will be from
      GU cancers. Identifying the differences in the occurrence of testicular,
      prostate, bladder, and renal cancer by age, race, sex, and geographic
      distribution and looking at trends over time are necessary for the development of
      etiologic hypotheses and appropriate health services.

PMID- 8290818
TI  - Testicular cancer.
AB  - Although testicular cancer accounts for approximately 1% of all male
      malignancies, it has a significant impact on the social, economic, and emotional
      status of the young population in which it occurs. TSE is the best available tool
      for early detection of testicular cancer. Only 15 to 20 years ago, testicular
      cancer was often fatal because of the rapidity of metastasis to the lungs and
      other vital organs. Because of progress in surgical technique and chemotherapy,
      it is today one of the most curable cancers. The use of serum markers and early
      diagnosis and treatment are of great importance in the management of testicular
      cancer.

PMID- 8290819
TI  - Cancer of the prostate.
AB  - Prostate cancer is the most common cancer in men and the second leading cause of
      cancer deaths. New advances in screening and imaging allow earlier diagnosis, and
      improved surgical techniques have reduced sexual dysfunction and incontinence
      that often resulted from radical prostatectomy. However, many questions remain.
      How can prostate cancer best be detected in an early curable form? What is the
      role of tumor markers? Who should be screened and how? What prognostic tools can
      help with decisions about appropriate therapy?

PMID- 8290820
TI  - Carcinoma of the bladder.
AB  - Over the past 20 years, advances in tumor staging, tumor biology, and therapeutic
      management have positively influenced both cure rates and overall survival of
      patients with bladder cancer. Treatment recommendations depend on the stage of
      the disease, the grade of tumor, likelihood of recurrence, and the patient's
      medical condition. These patients continue to be faced with treatment options
      that affect their physical, sexual, and psychosocial well-being.

PMID- 8290821
TI  - Renal cell carcinoma.
AB  - Complete surgical resection of renal cell cancer confined to the kidney offers a
      hopeful prognosis of long-term remission or cure. Metastatic renal cell cancer is
      not effectively managed through the traditional modalities of surgery,
      chemotherapy, hormonal therapy, or radiation therapy. Quantum leaps in the
      understanding of immunobiology and molecular genetics, as well as the elucidation
      and application of biologic response modifiers, have created a climate of renewed
      enthusiasm for defining more active regimens for the management of metastatic
      renal cell cancer. As long-term remission and cure are highly unlikely for the
      majority of individuals presenting with advanced disease, attention to quality of
      life issues such as symptom control, cost containment, and honesty is
      appropriate. In diseases such as metastatic renal cell cancer where no effective
      standard of therapy has been demonstrated, participation in well-designed,
      carefully executed clinical trials with adequate reimbursement is encouraged for
      all eligible candidates. Individuals challenged with living with metastatic
      kidney cancer are aware of the gradual or precipitous nature of their declining
      process and generally do not harbor unrealistic hope for longterm survival.
      However, pain relief and comfort are reasonable hopes, and striving for and
      attaining an optimal quality of life will sustain both the individual and
      caregiver.

PMID- 8290822
TI  - Continent urinary reservoirs.
AB  - With the increasing incidence of bladder cancer, many different operations have
      been devised to reconstruct the lower urinary tract in a continent fashion. The
      incontinent type of urinary reservoir (ileal conduit) has been a surgical
      preference for many years. However, the continent urinary reservoir (CUR),
      neobladder, and rectal bladder offer the capable and motivated patient an
      alternative to an incontinent permanent stoma. Nursing management of patients
      requiring diversional surgery requires continual updating of these specialized
      surgical procedures and unique aspects of care.

PMID- 8290823
TI  - Psychosocial and sexual implications of genitourinary cancers.
AB  - The ability to adjust to a cancer diagnosis varies widely and is modulated by
      factors such as premorbid functioning, availability of social support, and the
      meaning of the crisis in the life cycle of the individual. The specific site of
      the malignancy also plays an important role in adjustment. Major concerns for
      genitourinary malignancies are urinary continence, fertility, and sexuality.
      Issues of sexual body image and identity as men or women are frequent concerns.

PMID- 8290824
TI  - Pathways of development and progression in bladder cancer: new correlations
      between clinical observations and molecular mechanisms.

PMID- 8290825
TI  - Management of superficial transitional cell carcinoma of the bladder.
AB  - Intravesical therapy for the treatment of existing bladder cancer or for
      prophylaxis of recurrent disease should be chosen according to the stage of
      transitional-cell cancer. Papillary disease (stages Ta, T1) may be treated
      effectively with either an alkylating agent or with BCG. BCG is the agent of
      choice for the treatment of Tis, provided that the treatment course includes 12
      weekly and 12 monthly instillations.

PMID- 8290826
TI  - Critical review of radical cystectomy and indicators of prognosis.
AB  - The data would strongly suggest that, if local control can be established by
      either radical cystectomy or by transurethral resection, and if no distant
      disease is existing, that transurethral resection and radical cystectomy provide
      equivalent survival advantage. Our current dilemma lies in the inability to
      accurately determine the extent of disease as evidenced by the upstaging error
      that occurs following radical cystectomy. Thus, the treating physician must
      decide whether to abandon a therapeutic procedure such as radical cystectomy,
      which has the potential to cure higher local stage disease than may transurethral
      resection. It would appear that radical cystectomy as a single therapy remains
      the treatment of choice.

PMID- 8290827
TI  - A critical review of the role of definitive radiation therapy in bladder cancer.
AB  - The role of radiation therapy in the management of bladder cancer continues to be
      controversial. Attention to the issue of response to treatment, instead of
      overall survival, ultimate local control and quality of life, has hampered
      progress in determining the optimal-treatment strategy for patients with bladder
      cancer. Although the heterogeneity of bladder cancer has been recognized for some
      time now, the trend has been to seek one cure for all, rather than to use the
      available modalities selectively and optimally. The use of continent urinary
      diversion has made cystectomy more acceptable, but no form of diversion is as
      satisfying as a natural, well functioning bladder. The case against definitive
      XRT has been built on the lack of total radiosensitivity of transitional cell
      carcinoma. It is interesting that the lack of total chemosensitivity of bladder
      cancer and total curability with surgery has not prevented those modalities from
      being widely used. The recognition of the systemic nature of invasive bladder
      cancer has appropriately led to increased attention to the control of systemic
      disease. However, this has led to, at times, compromised local therapy. The use
      of primary or adjuvant chemotherapy should not impede the pursuit of optimal
      local therapy in patients with bladder cancer with the emphasis on the optimal
      quality of life. In parallel, the goal of bladder preservation and improved
      quality of life should not overshadow the importance of local tumor control.
      Because metastatic bladder cancer currently is an almost universally lethal
      disease, we should optimize the use of effective treatment modalities to achieve
      modest improvements in cure rate. The idea that definitive radiation therapy has
      no role in the management of bladder cancer exists in the minds of those who hold
      strong convictions and see an alternative view to their own as being
      controversial. We believe that attention should not focus on this controversy but
      on the recognition of the reality that the best management of bladder cancer is a
      shared responsibility among the oncologists of all disciplines. With this
      recognition, clinical research toward improving outcome for patients with bladder
      cancer will move forward.

PMID- 8290828
TI  - Adjunctive adjuvant or neoadjuvant chemotherapy for locally advanced bladder
      cancer: a critical appraisal of the present status.

PMID- 8290829
TI  - Options in urinary diversion: a review and critical assessment.

PMID- 8290830
TI  - [Cardiovascular prevention: lessons from epidemiological studies].

PMID- 8290831
TI  - [Meralgia paresthetica].

PMID- 8290832
TI  - [Parasitosis delirium or Ekbom's syndrome].

PMID- 8290833
TI  - [Neck tumors: struma].
AB  - Goiters are most commonly caused by increased, usually nodular growth of thyroid
      tissue ('simple' goiter), stimulation of thyroid growth by autoantibodies
      (Grave's disease) or thyroiditis. Rarer causes of goiter are malignant thyroid
      tumors and hereditary disturbances of thyroid hormone synthesis goiter: due to
      iodine deficiency should be found no longer in Switzerland because of the
      adequate iodine supplementation in this country. Differentiating the various
      types of goiters is usually possible on the basis of clinical signs and a few
      laboratory tests (e.g. measurement of thyroid antibodies). 'Simple' goiter is
      usually treated surgically. Hyperthyroid Grave's goiter is primarily treated with
      thyrostatic drugs, if it recurs; radioiodine of surgery are also used. Subacute
      thyroiditis causing goiter is treated symptomatically with analgesics anti
      inflammatory drugs, while patients with chronic thyroiditis are given thyroid
      hormones when hypothyroidism occurs. Malignant tumors of the thyroid are treated
      surgically; in some cases additional therapy with radioiodine is indicated.

PMID- 8290834
TI  - [Neck cysts].
AB  - Cystic neck alterations are discussed. Practically important guidelines and
      possible pitfalls are outlined. The importance of a thorough preoperative
      evaluation is stressed, in order to obtain optimal surgical results.

PMID- 8290835
TI  - [Infectious cervical adenopathy].
AB  - Cervical adenopathy is often found on examination, but rarely causes clinical
      problems. If the adenopathy persists for a longer period then three to four weeks
      and no infectious causes are found, further investigations are needed, especially
      to exclude a malignancy. The chronic infectious adenopathies are discussed:
      mycobacterial (tuberculous and atypical), toxoplasmosis, cat-scratch disease and
      actinomycosis.

PMID- 8290836
TI  - [Rare neck tumors: neurogenic tumors and carotid glomus tumors].
AB  - Among the rare tumors of the neck, neurogenic tumors and paraganglioma of the
      carotid body are discussed. Special emphasis is placed on a preoperative
      diagnosis of the carotid paraganglioma.

PMID- 8290837
TI  - [Malignant lymphoma of the neck, nose and pharyngeal region].
AB  - Malignant lymphomas (Hodgkin's and Non Hodgkin's Lymphoma) are often diagnosed in
      lymphoid structures of the head and neck region as part of either a localized or
      an already disseminated disease. Its careful work-up with histology and accurate
      staging is the base of a successful therapeutic strategy. With appropriate
      chemotherapy and/or radiotherapy, the primary aim is often cure of disease. Other
      diseases important for differential diagnosis are discussed.

PMID- 8290838
TI  - [Cervical lymph node metastases].
AB  - The investigative procedure of clinically diagnosed cervical lymph node
      metastases is discussed. Cervical lymph node metastases can be the first
      manifestation of a carcinoma. The corresponding primary tumor is diagnosed in the
      ENT area (mouth, pharynx, larynx) in 80% of the cases and in bronchi or esophagus
      in 10%; therefore, a detailed ENT examination and an upper panendoscopy must be
      undertaken. Wedge excisions of lymph node metastases are contraindicated, since
      they produce an artificial rupture of capsule and open the door to extranodal
      tumor growth. Excision of cervical lymph nodes, which are clinically related to a
      cervical lymph node metastasis, should only be carried out within the framework
      of a diagnostic and therapeutic concept.

PMID- 8290839
TI  - [Positron emission tomography (PET) in the preoperative evaluation of cervical
      lymph node metastasis of ORL cancer].
AB  - The distribution of specific radiolabeled biological compounds in tumor tissues
      can be imaged by positron emission tomography (PET). The substance used is
      fluorodeoxyglucose, labeled with the positron emitter fluorine-18. This substance
      is partly trapped in tumor cells with increased glucose metabolism. This
      noninvasive imaging technique allows to assess quantitatively and in three
      dimensions the extent of metastatic disease in ENT cancer. The case presented
      illustrates the important value we foresee for this new imaging modality in the
      presurgical staging of cervical metastatic disease of ENT tumors. Sensitivity and
      specificity of the PET-FDG imaging technique for the loco-regional staging of ENT
      cancer are, according to preliminary results of an ongoing, prospective clinical
      study, very high.

PMID- 8290840
TI  - [Lumbar spondylogenic (pseudoradicular) syndrome].

PMID- 8290841
TI  - [Migraine: what is new?].

PMID- 8290842
TI  - [Clinical assessment of temporomandibular joint disorders].

PMID- 8290843
TI  - [One anemia may hide another].

PMID- 8290844
TI  - [Pulmonary manifestations of hepatic diseases].

PMID- 8290845
TI  - [Management of obesity with simple means: valid or not?].

PMID- 8290846
TI  - [Urinary electrolytes: indications and interpretation].

PMID- 8290847
TI  - [The Sierre-Loeche Hospital--hospital of the 3rd millennium].

PMID- 8290848
TI  - [Inguinal hernia in adults: surgery under local anesthesia].

PMID- 8290849
TI  - [Immune response to various antiviral vaccines].

PMID- 8290850
TI  - [Fatal sub-fulminant hepatitis due to diclofenac].

PMID- 8290851
TI  - [Surgical revision of aseptic loosening of total hip arthroplasties. Why not
      wait].

PMID- 8290852
TI  - [Vertigo and the practitioner].

PMID- 8290853
TI  - Sleep state organization in the developing piglet during exposure to different
      thermal stimuli.
AB  - Sleep state changes in response to different thermal stimuli were investigated in
      newborn piglets between 2 and 10 days of age. Test animals were exposed to cold
      air (7-12 degrees C) and warm air (27-33 degrees C) around the face, while the
      remainder of the body was kept at first warm (normothermic) then hyperthermic. A
      separate group of animals was studied under normothermic conditions (control) for
      the duration of the study. Piglets showed typical changes in sleep state patterns
      characteristic of rapid maturation over the first 10 days of development. It was
      found that both the amount of rapid eye movement (REM) sleep and, in some cases,
      the duration of REM episodes increased in response to facial cooling regardless
      of rectal temperature. However, hyperthermia with warm air exposure caused a
      significant decrease in the amount of REM sleep but not in the duration of REM
      episodes. It is suggested that an infant placed to bed in a cold room or exposed
      to a draft might also experience a greater amount of REM sleep than an infant
      placed to sleep in a warm draft-free room.

PMID- 8290854
TI  - Upper airway resistance syndrome: sick, symptomatic but underrecognized.
AB  - Upper airway resistance syndrome (UARS) appears to be underrecognized or at least
      underreported in the medical literature. We have found that these children may
      suffer the same, if not more, severe consequences of sleep disordered breathing
      than obstructive sleep apnea patients. Seventy-five infants and children were age
      and gender matched from a heterogeneous patient population in Southern
      California. Each patient underwent clinical polysomnography. Twenty-five patients
      were in each of three groups. Group one patients were clinician referred to the
      sleep clinic and were found to be free of significant sleep pathology. Group two
      patients had UARS. Group three patients had frank obstructive sleep apnea. The
      three groups differed on respiratory, sleep and snoring parameters. A heuristic
      is presented to help clinicians tailor their treatment approach and sleep
      scientists to test the model to aid in the understanding of UARS.

PMID- 8290855
TI  - Circadian rhythms in sleep and wakefulness and in salivary melatonin and cortisol
      concentrations in mothers of term and preterm infants.
AB  - We compared the effects of the demands of term and preterm infants on the daily
      rhythms of sleep and wakefulness and salivary melatonin and cortisol
      concentrations in mothers for up to 5 months after either birth (term group) or
      arrival of the infant home (preterm group). Although there were relatively small
      differences between the term and preterm groups in the daily patterns of infant
      sleep-wake behavior, there were more marked differences in the maternal sleep
      wake parameters. During the first 8 weeks after the arrival of the infant home,
      the mothers of preterm infants had significantly less time asleep and fewer sleep
      bouts per 24 hours than did the mothers of term infants. The mothers of preterm
      infants spent a significantly longer proportion of each night awake (30-40%) for
      the first 8 weeks than did the mothers of the term infants (20-30%). There was
      also a significant difference between the term and preterm groups in the effect
      of time of day on maternal salivary melatonin concentrations. In the term group,
      maternal melatonin concentrations were higher at night (10 p.m.-6 a.m.) than at
      any other time of day. In contrast, in the preterm group maternal melatonin
      concentrations between 10 p.m. and 6 a.m. were only higher than those measured
      between 6 a.m. and 2 p.m. Salivary cortisol concentrations were significantly
      higher in the mothers of preterm infants than in the mothers of term infants
      throughout the 10-week study period, but the peak in salivary cortisol
      concentrations occurred between 2 a.m. and 10 a.m. in both the term and preterm
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290856
TI  - Patterns of sleep episodes in young and elderly adults during a 36-hour constant
      routine.
AB  - The deterioration of nocturnal sleep and increase in daytime napping that
      accompany aging may represent changes in homeostatic or circadian aspects of
      sleep regulation. We addressed these possibilities by examining patterns of
      unintended sleep episodes, subjective sleepiness and mood during 36 hours of
      constant wakeful bed rest in 17 healthy 20-30-year-olds (n = 9 men, n = 8 women)
      and 18 healthy 80-year-olds (n = 11 men, n = 7 women). Subjects had continuous
      electroencephalographic (EEG) monitoring and core body temperature measurements
      and completed visual analog scale ratings of sleepiness and mood each hour. Young
      and elderly groups both showed significant linear and circadian trends in sleep
      episodes across the interval. Group x time interaction effects revealed a
      stronger linear trend in the young vs. elderly group, but no difference in
      circadian trends. Analysis of age groups by sex demonstrated more complex
      interactions, with elderly men showing weaker rhythmic (circadian) trends than
      elderly women. Subjective ratings of sleepiness and mood showed no difference in
      temporal trends between young and elderly groups. These data support the
      hypothesis that age-related sleep changes result primarily from decreases in
      homeostatic, rather than circadian, sleep propensity. They also confirm the
      presence of sex differences in sleep patterns among the elderly and support the
      distinction between objective and subjective measures of sleepiness.

PMID- 8290857
TI  - When the human circadian system is caught napping: evidence for endogenous
      rhythms close to 24 hours.
AB  - It is now well acknowledged that napping constitutes an inherent component of the
      human circadian system. To date, however, few studies have examined the effects
      of spontaneous napping on human free-running rhythms. This study investigated the
      free-running circadian periods of rest/activity and body core temperature in a
      group of young subjects who were permitted to nap during their time in isolation.
      Based on the frequency of self-reported sleep bouts, subjects were classified as
      Nappers or Nonnappers. Nappers exhibited free-running rhythms in both
      rest/activity and body core temperature that were not significantly different
      from 24 hours. Nappers showed a tendency for shorter free-running periods in both
      variables, when compared with Nonnappers. These findings emphasize the need for
      careful reassessment of data obtained from traditional free-run protocols.

PMID- 8290858
TI  - Pharmacologic alteration of the perception of being awake or asleep.
AB  - In order to further explore the effects of triazolam on the subjective experience
      of sleeping, we awakened chronic insomniacs with an electronic tone at five
      points across the night after having administered placebo and three doses of
      triazolam (0.125, 0.25 and 0.375 mg). Triazolam reduced the likelihood of
      subjects reporting that they had been awake by about half. Drug effects were most
      evident in the period 5 minutes after "lights out", at which time there was a
      reduction in the certainty of the subjects' response; the investigator's ratings
      of mental activity on the dream complexity scale rose from a rating of "awake"
      following placebo to the borderline of sleep following triazolam. After triazolam
      administration, subjects reported less certainty about their descriptions of
      mental imagery. These data are consistent with a hypothesis that during sleep,
      and particularly at the threshold of electroencephalogram (EEG) defined sleep,
      triazolam induces cognitive changes in which the subjective distinction between
      waking and sleep becomes less clear. Several approaches are suggested to
      determine whether these effects are related to retrospective subjective reports
      of hypnotic efficacy.

PMID- 8290859
TI  - The effects of ritanserin on mood and sleep in abstinent alcoholic patients.
AB  - A trial was carried out to determine the effect of ritanserin or a placebo on
      sleep and mood in two groups of abstinent alcoholic patients. Their condition was
      characterized by both alcohol dependence and dysthymia, associated with a
      personality disorder. They were included in the study after 30 days of sobriety.
      Ritanserin was given at a daily dose of 10 mg for 28 days and was preceded (10
      days) and followed (2 days) by a placebo. Plasma ritanserin concentration after
      administration of the 28th dose was higher than after the first dose. Peak levels
      of ritanserin from the first to the 28th dose increased approximately three-fold.
      In the ritanserin group there was a reduction of total waking time. Total sleep
      time increase was associated with significantly larger amounts of nonrapid eye
      movement sleep. Slow wave sleep and rapid eye movement sleep (in minutes or as a
      percent of total sleep time) were not significantly modified. Patients on
      ritanserin achieved a progressive improvement of their dysthymia. As compared to
      the placebo group, a statistically significant decrease of the Hamilton Rating
      Scale for Depression and Hamilton Rating Scale for Anxiety was found in the
      ritanserin group after 1 week of treatment. The absence of an effect in the
      placebo-treated group suggests that the clinical response and sleep improvement
      were mainly related to ritanserin administration.

PMID- 8290860
TI  - Comparison of the effect of zopiclone and brotizolam on sleep EEG by quantitative
      evaluation in healthy young women.
AB  - We studied the effect of brotizolam (BRO) (0.25 mg) and zopiclone (ZPC) (7.5 mg)
      on the sleep electroencephalograms (EEG) of seven healthy young women (ages 20-21
      years). In addition to conventional sleep scoring, we performed spectral analysis
      of EEG wave forms using the Fast Fourier Transformation (FFT) method. Four weeks
      following two consecutive polysomnographic recordings with placebo administration
      (for baseline data), polysomnography with BRO or ZPC administration was performed
      on the subjects who were then crossed over to polysomnography with ZPC or BRO,
      respectively, 1 week later. Total rapid eye movement (REM) time was decreased on
      the ZPC and BRO nights and REM latency was prolonged on the ZPC night compared
      with baseline (BL) night. Other parameters, however, were not significantly
      different between the drug nights and the BL night. There were also no
      differences in standard scoring results between both drug nights. FFT analysis
      revealed significant differences in total power density percentage and mean power
      density percentage in both nonrapid eye movement (NREM) and REM sleep between ZPC
      and BRO nights and between both drug nights compared to the BL night. Total power
      density and mean power density per epoch showed significant decreases in the
      theta band (6.0-8.0 Hz) and sigma band (12.0-14.0 Hz) on the ZPC night versus the
      BRO night or BL night during specific NREM periods. The results of this study
      corroborate previous reports that suggest computer-aided quantitative
      electroencephalography aids in differentiating specific effects of hypnotics and
      other central-nervous-system-acting agents on the sleep EEG.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8290861
TI  - The second generation of nasal continuous positive airway pressure devices. Are
      they created equal?
AB  - Nasal continuous positive airway pressure (NCPAP) is considered the preferred
      medical treatment of obstructive sleep apnea. Because NCPAP exerts its beneficial
      effects by maintaining positive airway pressure, we proposed to test the ability
      of the newer "second generation" NCPAP machines to maintain a constant airway
      pressure during simulated breathing on a lung model. Each of the seven new NCPAP
      devices tested were examined under conditions of changing inspiratory flow, end
      expiratory pressure (EEP) and resistance added to the patient end of the NCPAP
      hose. During inspiration airway pressure fell and in expiration it increased
      relative to the EEP in all machines. Using the standard NCPAP hose and a
      breathing pattern consistent with normal breathing during sleep, the maximum
      decline in pressure during simulated inspiration and excess pressure during
      simulated expiration was -0.5 cm H2O and 0.6 cm H2O, respectively. Adding
      resistance, increasing inspiratory flow but not EEP exaggerated this effect. All
      of the machines behaved similarly in this regard. Further, the performance of the
      NCPAP devices did not deteriorate after 6 hours of uninterrupted operation. We
      conclude that the second generation NCPAP machines may be interchanged without
      another laboratory trial to readjust the EEP.

PMID- 8290862
TI  - Use of a face mask in the measurement of resting ventilatory parameters and mouth
      occlusion pressures.
AB  - A recent study has suggested that mouth occlusion pressure (MOP) could be
      measured during sleep by using a face mask. The purpose of the present study was
      to examine the effects of a face mask on MOP and resting ventilatory parameters
      (RVP). Measurements of MOP and RVP were made by three different methods; while
      breathing through a mouthpiece with nose-clip (MP+NC), through a face mask
      breathing through the mouth only (FM/mouth), and through a face mask breathing
      through the nose only (FM/nose). There was a significant difference in several
      RVP parameters between MP+NC and FM, but no significant difference in MOP between
      different methods. Use of FM for the measurement of MOP appears to be warranted,
      and with regard to RVP consideration needs to be given to the differences found
      between MP+NC and FM.

PMID- 8290863
TI  - Recurrent attacks of unconsciousness with diffuse EEG alpha activity.
AB  - A 45-year-old patient presented with recurrent attacks of unconsciousness, which
      resembled sleep. However, EEG recordings during these attacks showed diffuse,
      frontal-dominant 10-Hz alpha activity. Both the attacks and EEG changes reversed
      promptly with intravenous flumazenil, but not with methylphenidate, atropine or
      placebo. The attacks could not be prevented with methysergide, flumazenil,
      clonidine, piracetam or phenytoin. Laboratory investigations revealed a temporal
      lobe arachnoid cyst, a distal motor and sensory polyneuropathy, abnormal auditory
      evoked responses during the attack, an abnormal silent period latency and
      abnormal melatonin regulation. Similar attacks were reported by history in two
      siblings and in the proband's late father. It is postulated that the attacks of
      unconsciousness could involve gamma-aminobutyric acid- (GABA)-mediated
      mechanisms.

PMID- 8290864
TI  - The nasal dilator Nozovent and its effect on snoring and apneas.

PMID- 8290865
TI  - Cell death and regeneration of renal proximal tubular cells in rats with
      subchronic cadmium intoxication.
AB  - Male Sprague-Dawley rats were injected subcutaneously with 0.6 mg cadmium
      (Cd)/kg/day for 8 wk. The subsequent changes in renal proximal tubules were
      studied histologically, histochemically, and ultrastructurally. The urinary and
      tissue Cd concentrations were determined by atomic absorption spectrophotometry.
      After 4 wk of exposure, apoptosis was observed predominantly in segment S3 along
      with epithelial regeneration in the affected tubules, and these changes gradually
      became more pronounced as the experimental period was prolonged. The apoptotic
      cells were shed into the lumen and were found to contain a large quantity of Cd.
      Apoptotic cells were counted in paraffin sections after various periods of
      exposure to Cd. Nuclear bromodeoxyuridine uptake, mitotic count, and nuclear
      density were used as indicators of tubular regeneration. A correlation was found
      between the numerical increase of apoptotic cells and the rate of urinary Cd
      excretion, and the rate of increase in the tissue Cd concentration had a tendency
      to reduce after 4 wk as the rate of urinary Cd increased. These observations
      suggest that apoptosis might be helpful for the efficient excretion of Cd into
      urine. Progressive increases in the preceding indicators of regeneration were
      observed. From our results, it appears that Cd-induced tubular damage, i.e., cell
      deletion due to apoptosis, is reversible as a result of marked epithelial
      regeneration. On the basis of these histological changes, the critical
      concentration of Cd required to produce renal tubular damage was estimated to be
      600 micrograms/g dry tissue.

PMID- 8290866
TI  - Influence of dietary protein concentration on severity of nephropathy in Fischer
      344 (F-344/N) rats.
AB  - Nephropathy is an age-related spontaneous disease of most rat strains, and
      protein content of diet may affect the severity. The purpose of this study was to
      determine the effect of a 15% protein nonpurified diet on body weight and
      severity of nephropathy in comparison to a 23% protein NIH-07 diet. Groups of 25
      male and 25 female Fischer-344 (F-344) rats, 6 wk of age, were fed the 23 or 15%
      protein diet ad libitum for 2 yr. Rats were weighed at 1-4-wk intervals, and mean
      body weights were determined. Water consumption measurements and urinalysis were
      done at approximately 3-mo intervals during the second year of the study. At the
      end of the 2-yr study, kidneys from all rats, including those that died or were
      euthanatized after the eightieth week of the study, were examined by light
      microscopy and graded for severity of nephropathy as grades 1-4 (minimal, mild,
      moderate, marked). Growth patterns and the maximum body weights attained by each
      sex fed the 23 or 15% protein diet were not significantly different. The severity
      of nephropathy in male rats was significantly higher when fed the 23% protein
      diet (2.8 moderate to marked) compared to the 15% protein diet (1.3 minimal to
      mild). The severity of nephropathy in female rats increased slightly when fed the
      23% protein diet (1.5 minimal to mild) compared to the 15% protein diet (1.0
      minimal).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8290867
TI  - The high incidence of atrial thrombosis in mice given doxorubicin.
AB  - Doxorubicin (DX)-treated mice represent an animal model for studying new drugs
      for heart disease. Coincidentally, in the collection of damaged myocardial
      tissue, thrombosis was detected in the atrium. The incidence reached 75% in mice
      given 4 mg/kg DX iv 10 times. They were white thrombi consisting of the fibrin,
      platelets, and neutrophils. Cardiac muscle damage was more prominent in the atria
      than in the ventricles. Light microscopically, vacuolization and degeneration of
      atrial myocytes and interstitial inflammatory cell infiltration were observed.
      Electron microscopy revealed dilatation of the sarcoplasmic reticulum and an
      increase in number of normal and/or degenerate mitochondria. Inflammation
      extended from the cardiac muscle to the endocardium. The cause of atrial
      thrombosis in DX-treated mice is unknown but may relate to endocardial damage and
      changes of blood flow in the atrium secondary to cardiac muscle damage. DX
      treated mice could serve as an experimental animal model for the evaluation of
      efficacy and toxicity of antithrombotic or antiplatelet drugs.

PMID- 8290868
TI  - Multinucleated hepatocytes induced by rifabutin in rats.
AB  - Rifabutin is an antibiotic of the rifamycin class, which is particularly active
      against mycobacteria, including those that occur in AIDS patients. Because
      clinical use will include long-term therapy, an extensive battery of long-term
      toxicity studies was carried out by the oral route, including carcinogenicity
      studies. An interesting feature was the occurrence of multinucleated hepatocytes
      (MNHs) in the rat. In some instances, as many as 25 nuclei occurred in a single
      cell. Light microscopy revealed a large hepatocyte with normal eosinophilic
      staining. The multiple nuclei stained like those present in the surrounding
      normal cells. Electron microscopy showed no abnormalities of the nuclei and no
      cell membranes within the cytoplasm. The customary organelles were present. MNHs
      were dose- and sex-related, starting from 10 mg/kg/day and being more evident in
      males. They began to appear after 5 wk of treatment and persisted over long
      periods of recovery (12 mo), without showing any tendency for cell proliferation.
      The life-span of MNHs was similar to that of normal hepatocytes. MNHs were
      present in the carcinogenicity study, but there was no increase in liver tumors.
      MNHs did not occur in mice or monkeys treated with rifabutin, nor did they occur
      in response to treatment with rifampin. The effect appears to be specific to the
      rat.

PMID- 8290869
TI  - Effect of alternate-day hydrocortisone therapy on the immunologically immature
      rat. I: Effect on blood cell count, immunoglobulin concentrations, and body and
      organ weights.
AB  - The effect of 400 mg/M2/day of hydrocortisone, given alternatively from day 7 to
      day 19, was studied in the immunologically immature rat, a steroid-sensitive
      species. Animals, sacrificed 2 days following the completion of treatment,
      suffered from an underweight thymus and spleen, leucocytosis, and peripheral
      lymphocytopenia, probably not due to redistribution of lymphocytes from blood to
      tissues. In addition, a significant decrease in serum IgM concentration,
      reflecting a deficit in primary immune response, was evidenced. Although the
      percentage of lymphocytes returned to normal in rats sacrificed 23 days after
      treatment, an overweight thymus and spleen and persistent leucocytosis may
      reflect a compensatory overactivity of the developing immune system. In contrast,
      serum IgM concentration increased, but to a value less than normal. An indirect
      effect of hydrocortisone on lymphocytes through its action on thymus, as well as
      a direct effect on B cells, is suggested. Unlike humans, alternate-day steroid
      therapy delayed the normal growth pattern of rat, with a defective rate of growth
      only during the treatment period.

PMID- 8290870
TI  - Effect of alternate-day hydrocortisone therapy on the immunologically immature
      rat. II: Changes in T- and B-cell areas in spleen.
AB  - The histologic effect of 400 mg/M2/day of hydrocortisone, given alternatively
      from day 7 to day 19 after birth, was studied on the spleen of the
      immunologically immature rat. Two days after the cessation of treatment, the
      periarteriolar lymphatic sheaths were found to be largely depleted of small
      lymphocytes. Immunoperoxidase studies confirmed a depletion of T lymphocytes. The
      effects of hydrocortisone on the thymus seem to be more important than its direct
      lymphocytolytic effect in producing this splenic lesion. In contrast, no apparent
      change in the number of medium-sized B lymphocytes in the marginal zone was
      detected. Medium-sized B lymphocytes of the spleen, reported to be responsible
      for IgM synthesis, appeared to be subjected to a different mechanism of
      hydrocortisone action, other than lysis, resulting in a decrease in antibody
      production. Primary follicles were not seen in spleens of hydrocortisone-treated
      rats. Twenty-three days after treatment, spleens had a histologically normal
      appearance.

PMID- 8290871
TI  - Effect of alternate-day hydrocortisone therapy on the immunologically immature
      rat. III: Changes in T- and B-cell areas in lymph nodes.
AB  - The histologic effects of the alternate-day hydrocortisone therapy (400 mg/M2
      from day 7 to day 19 after birth) were studied on the mesenteric lymph nodes of
      immunologically immature rats. In rats sacrificed 2 days following the cessation
      of therapy, depletion of lymphocytes of the thymus-independent area was apparent.
      Smaller lymphocytes were more susceptible to the effect of hydrocortisone than
      larger ones. The absence of primary follicles, normally present at this age,
      suggested a possible retardation in development of the immune system. B
      lymphocytes appeared to be the target of the direct lymphocytolytic effect of
      hydrocortisone. In rats sacrificed 23 days following the treatment, immunological
      maturity was achieved, indicating the reversibility of the hydrocortisone effect.

PMID- 8290872
TI  - Intratubular spermatic seminoma in a Fischer-344 rat.
AB  - A case of a spontaneous intratubular spermatic seminoma is described in a 98-wk
      old Fischer-344 (F-344) rat. The differential diagnosis of spermatic seminoma
      from the other morphological forms of the tumor was based on the recognition of 3
      cell types. The tumor cells were positive for S-100 antigen and cytokeratin. To
      the best of our knowledge, this is the second case of a seminoma reported in an F
      344 rat and the first dealing with electron microscopic and immunohistochemical
      features of this tumor.

PMID- 8290873
TI  - A quantitative cytochemical study on the pathogenesis of streptozotocin-induced
      epithelial tumors in rat kidney.
AB  - We investigated the development of early neoplastic lesions preceding the
      appearance of kidney epithelial tumors in rats treated with a single iv injection
      of 35 mg/kg of streptozotocin (STZ). Most of these lesions were associated with
      segments of atrophied and regenerative nephrons surrounded by a thick basal
      membrane that appear precociously in chronic progressive nephropathy.
      Cytochemical periodic acid-Schiff, Alcian blue, and colloidal iron reactions did
      not indicate an excessive storage of glycogen or acid mucopolysaccharides in
      early neoplastic lesions and tumors. Quantitative cytochemistry of mitochondrial
      succinate, alpha-glycerophosphate, and reduced nicotinamide adenine dinucleotide
      dehydrogenases revealed a shift in metabolism toward glycolysis in atrophied and
      regenerative nephrons as well as in early neoplastic lesions and tumors. These
      correlative cytomorphological and cytochemical findings raise the possibility
      that changes associated with the initial stages of chronic progressive nephrosis
      may provide favorable conditions for the selective growth of STZ-initiated cells
      that generate focal collections of proliferating cells and then progress to tumor
      growth. Tumor prevalence was remarkably constant in animals sacrificed 33, 48,
      and 54 wk after treatment, suggesting that the prominent inflammatory and
      scarring reaction later developing in the course of progressive nephrosis might
      contribute to control the growth of STZ-induced cancer.

PMID- 8290874
TI  - Modifying effects of chemicals on the development of liver preneoplastic
      placental glutathione S-transferase positive foci in analbuminemic and Sprague
      Dawley rats.
AB  - Nagase analbuminemic rats (NARs) were compared to the Sprague-Dawley (SD) stock
      in a medium-term assay system for hepatocarcinogenesis regarding their
      susceptibilities to the influence of chemicals on the development of glutathione
      S-transferase, placental form, positive (GST-P+) foci. Two weeks after initiation
      with diethylnitrosamine (DEN), the animals were exposed alternatively to 0.06% 3'
      methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB), 50 ppm DEN, 0.25% ethionine, 1%
      clofibrate, and 1% butylated hydroxyanisole (BHA) for a 6-wk period. Adequate
      controls included groups only initiated with DEN or treated with each test
      compound alone. For evaluation of the modifying potential of the chemicals,
      indices were generated by using the mean values obtained for number and area of
      GST-P+ foci after each treatment. Comparison between these indices suggests that
      SD rats were relatively more sensitive than NARs to the modifying effects of
      complete carcinogens (3'-Me-DAB and DEN). The strains were similarly-susceptible
      to the promoting influence of ethionine, a nongenotoxic carcinogen. The
      inhibitory influence of BHA was more intense in NARs, whereas in both strains
      clofibrate was associated to similarly reduced values for number and area of GST
      P+ foci. The degree of susceptibility of each strain to the modifying influence
      of chemicals on foci development depended on the chemical agent investigated.

PMID- 8290875
TI  - Reactivity of young and old human enamel to demineralization.
AB  - The aim of this study was to determine the susceptibility of newly erupted and
      old permanent teeth to artificial, caries-like attacks. Two groups of caries-free
      teeth were used. Group 1 consisted of 38 teeth extracted for orthodontic reasons
      (9-12-yr-old children); group 2, of 40 teeth extracted for periodontal reasons
      (45-65-yr-old patients). After thorough cleaning, a test window was isolated on
      the incisal two-thirds of the buccal surface. After demineralization with 6% HEC
      gel at pH 4.9 for 8 days, longitudinal ground sections were prepared for
      imbibition studies in polarized light and for secondary ion mass spectrometry
      (SIMS). In the young teeth, the lesions appeared to be uniform in their extension
      in the enamel, whereas the old teeth showed less marked and thinner surface zones
      and greater depth of the positively birefringent body of the lesion. Polarized
      light microscopy and SIMS data support the hypothesis that there are different
      enamel pathways in the initiation of the natural carious process.

PMID- 8290876
TI  - Polymorphonuclear leukocyte chemiluminescence induced by Actinobacillus
      actinomycetemcomitans and Haemophilus aphrophilus in serum and saliva.
AB  - The ability of different strains of Actinobacillus actinomycetemcomitans (A.a.)
      and Haemophilus aphrophilus (H.a.) to trigger activation of an oxidative burst in
      human polymorphonuclear leukocytes (PMNL) was examined by measuring the luminol
      amplified light emission--chemiluminescence (CL)--from these cells. Bacterial
      cells were incubated with PMNL from one healthy subject, in the presence of
      either active serum, heat-inactivated serum, saliva, or saliva and active serum.
      In the presence of active serum, all five H.a. strains and two out of five A.a.
      strains triggered a CL response. The CL induced in the presence of heat
      inactivated serum was considerably less than that achieved with fresh serum. In
      the presence of only saliva, all strains induced considerably weaker CL responses
      than those induced in the presence of saliva with active serum. In the presence
      of serum, intracellular reactions appeared to be the main source of CL, while
      addition of saliva and active serum increased the extracellular CL. The results
      indicate that strain-dependent differences exist among A.a. strains in their
      ability to trigger the oxygen-dependent bactericidal mechanisms of human PNML. In
      contrast, the CL patterns of H.a. strains were equivalent. Various factors in the
      environment, such as activated complement and salivary compounds, affect the
      interaction of these species with neutrophils.

PMID- 8290877
TI  - Normal histologic features of domestic ferret periodontium.
AB  - The normal histologic features of the periodontal tissues in 17 domestic ferrets
      (10 male and 7 female) are described. The following teeth were histologically
      evaluated: canines, the maxillary third premolar (P3), the mandibular fourth
      premolar (P4), the carnassial teeth (P4 in the maxilla and the first molar, M1,
      in the mandible) and the next molar after the carnassials (M1 in the maxilla and
      M2 in the mandible). After histologic preparation for light microscopy, the
      sections were analyzed at magnifications of x 20 and x 100. The histometric
      measurements performed were 1) distance between the cementoenamel junction (CEJ)
      and the alveolar bone crest, 2) distance between CEJ and the most coronal
      connective tissue, 3) root length, 4) width of the periodontal ligament at three
      different locations along the root surface, and 5) cementum layer thickness at
      the most apical portion of the root. The number of sections exhibiting root
      resorption was counted. The results gave the normal values of some common
      periodontal variables and suggested a possible future use of the domestic ferret
      as an alternative experimental animal in periodontology.

PMID- 8290878
TI  - DNA probe detection of periodontopathogens in advanced periodontitis.
AB  - Species-specific DNA probes were used to determine the presence of Actinobacillus
      actinomycetemcomitans (A.a.), Porphyromonas (Bacteroides) gingivalis, Prevotella
      intermedia, Treponema denticola, Eikenella corrodens, Fusobacterium nucleatum,
      and Wolinella recta in subgingival plaque from deep pockets/sites of patients
      with advanced periodontitis. The subjects were 20 patients with severe adult
      periodontitis, 13 men and 7 women (mean age 45.6 +/- 6.7 yr). For each subject, 9
      10 subgingival sites with the deepest probing depths from each quadrant were
      sampled by the paper point method, a total of 198 sites, with mean probing depth
      7.2 +/- 1.6 mm and clinical attachment level 9.5 +/- 2.7 mm. A.a. was present in
      at least one site in 75% of the subjects; P. gingivalis was found in 95%; P.
      intermedia and W. recta were found in 90%, respectively; and T. denticola, E.
      corrodens, and F. nucleatum were found in all subjects. In the 198 samples, A.a.
      was detected in 25.8%, P. gingivalis in 51.5%, P. intermedia in 64.1%, T.
      denticola in 60.6%, E. corrodens in 72.9%, F. nucleatum in 74.7%, and W. recta in
      65.7%. The predominant combination was the simultaneous presence of P.
      intermedia, T. denticola, E. corrodens, F. nucleatum, and W. recta in 89.5% of
      the subjects and 46.8% of the sites. Of these sites, 51.1% showed the combined
      presence of P. gingivalis and 28.4% that of both A.a. and P. gingivalis. None of
      the seven bacteria could be detected in 14.4% of the total sites sampled. The
      present study indicates that severe destructive adult periodontitis is a
      multibacterial infection and that certain combinations of periodontopathogens
      seem to be important in the pathogenesis of the disease.

PMID- 8290879
TI  - Rapid bony healing in localized juvenile periodontitis: a case report.
AB  - A 16-yr-old man with localized juvenile periodontitis was treated in one single
      surgical treatment visit. No adjunctive chemotherapy, implant material, or guided
      tissue regeneration (GTR) was used. Excellent bone repair was seen after 14 wk at
      the sites of the vertical periodontal lesions. The rapid healing could have been
      due to the treatment method, the youth of the patient, or the type and form of
      the bony defects. Radiographic control seems to be indicated 12-14 wk after
      surgical treatment.

PMID- 8290880
TI  - Molecular forms and concentration of fibronectin and fibrin in human gingival
      crevicular fluid before and after periodontal treatment.
AB  - A total of 23 periodontitis-affected sites from seven adults was selected for the
      study. Crevicular fluid (CF) samples were collected with paper strips before
      treatment (scaling, root planing, and curettage) and 2, 5, 10, 20, and 40 days
      after treatment. Each sample was eluted into sterile saline and two aliquots were
      drawn for gel electrophoresis: one for fibronectin and one for fibrin analysis.
      Peptides were transferred to nitrocellulose membranes, and molecules were
      detected by specific antibodies. The proportions of different molecular forms of
      fibronectin and fibrin were analyzed by laser densitometry. Plaque Index, Papilla
      Bleeding Index, and pocket depth were recorded before and 40 days after
      treatment. Radiologic bone loss was estimated from orthopantomograms. Two days
      after treatment, an increase was seen in the proportions of intact fibronectin,
      fibronectin fragments larger than 70 kDa, and fibrin-positive material with a
      greater molecular mass than intact fibrin. Between days 5 and 10, the proportions
      of these large fragments decreased. The highest fibronectin and fibrin
      concentrations were seen 10 days after treatment. These changes probably reflect
      degradation of the subgingival fibrin clot formed after treatment, and indicate
      resolution of the clot during the first 10 days of healing. This agrees well with
      previous observations of CF plasmin activity and concentration of collagen
      synthesis markers in CF after periodontal treatment, and with the histologic
      changes seen during periodontal healing. Results of the present study, together
      with earlier reported findings of collagen synthesis after periodontal treatment,
      also support the hypothesis of sequential appearance of fibronectin and collagens
      during the process of wound healing.

PMID- 8290881
TI  - Rearing of Swedish, Norwegian, and Norwegian Sami children.
AB  - A total of 362 3-yr-old Swedish, Norwegian, and Norwegian Sami (Lapp) children
      were examined, and their parents were asked about their children's present and
      previous sucking habits and how long they had been breast-fed and bottle-fed.
      They were also asked what the children's age was when porridge or pureed food or
      food with a soft chewing resistance was introduced, and when more ordinary foods
      such as well-diced meat and potatoes were introduced. The study revealed that
      breast-feeding has increased greatly both in prevalence and in duration in Sweden
      during the last decades. Despite this, Swedish children were breast-fed for a
      significantly shorter time than Norwegian children. The longest breast-feeding
      times were noted for Sami children. Swedish children were bottle-fed two to three
      times longer than Norwegian children. Sucking habits were correlated to breast
      feeding only for Sami children.

PMID- 8290882
TI  - Miconazole chewing gum for treatment of chronic oral candidosis.
AB  - A chewing gum containing the antifungal drug miconazole may be convenient for
      topical treatment of oral candidosis. Therefore a trial was performed to examine
      the effect and tolerance of miconazole chewing gum in comparison with miconazole
      gel in the treatment of oral candidosis. The study group consisted of 32 patients
      with oral candidosis harboring yeasts, predominantly Candida spp. Half of the
      patients chewed one piece of chewing gum (dose: 3.6 mg of miconazole) four times
      daily; the other half dispersed a 2% gel (dose: 50 mg of miconazole) in the oral
      cavity four times daily. After 6 wk of treatment, there was no clinical evidence
      of yeast infection in either of the two groups. No significant differences
      between the two groups were found in clinical, mycologic, and cytologic
      investigations conducted after 3 and 6 wk of treatment or at the follow-up
      examination 4 wk after termination of the treatment. The results indicate that
      miconazole released from chewing gum is as effective as miconazole gel. The
      chewing gum reduced the dosage of miconazole for treatment of oral candidosis,
      and the patients approved the chewing gum as a pleasant medicament.

PMID- 8290883
TI  - Microvasculature of the dorsum of the rat tongue: a scanning electron microscopic
      study using corrosion casts.
AB  - The purpose of this study was to examine the microvascular system of the dorsum
      of the rat tongue in relation to the subepithelial connective tissue relief.
      Methylmethacrylate corrosion casts of the vasculature as well as specimens in
      which the epithelium had been removed were prepared and examined by scanning
      electron microscopy (SEM). The SEM images revealed four distinct layers in the
      vasculature of the lamina propria. Superficially, Layer 1 comprised the
      irregularly shaped ends of capillary loops. Layer 2 consisted of parallel
      ascending and descending capillaries. These two layers were drained by the
      subjacent Layer 3, a fish-net-like venous plexus. More deeply, Layer 4 contained
      arterioles ascending from the muscular layers of the tongue. The vessels of
      larger papillary structures formed cylindric networks supplied by several
      arterioles and drained through a single venule to the venous plexus in Layer 3.
      At their base, the capillary loops often showed a constriction, suggestive of a
      sphincter. Arteriovenous anastomoses were rare. The epithelium-connective tissue
      interface showed short conical papillae as well as larger papillary structures
      which corresponded in both distribution and size to the capillary loops found in
      the vascular casts. The results confirm that the tongue is highly vascularized
      and demonstrate that the vascular supply to the papillae, taste buds, and other
      surface structures forms a highly organized and specific system which is adapted
      to the specific functions of this organ in the rat.

PMID- 8290884
TI  - Covariation of some factors associated with occlusal tooth wear in a selected
      high-wear sample.
AB  - The aim of the present study was to investigate the significance of some factors
      associated with occlusal tooth wear in a selected high-wear Swedish sample. The
      material comprised 59 subjects having a mean age of 35 yr within the range 16-70
      yr, the criteria for selection being a full or nearly full complement of natural
      teeth, and the presence of definite clinical signs of occlusal wear. A dentition
      wear index was derived from a tooth-by-tooth evaluation of casts. The results
      showed that men had significantly greater wear than women. Other factors which
      were found to correlate significantly with increased occlusal wear were: age,
      increased bite force, decreased occlusal tactile sensitivity, increased endurance
      time, and reduced tendency for crowding in the dental arches. In the salivary
      analysis, it was found that low buffer capacity and low rate of secretion were
      significantly correlated with high wear. Cephalometric variables shown to be
      correlated with increased wear were retroclination and position of maxillary
      incisors, and greater interincisal angle. The results from this study also
      suggest that the associations of attrition with certain dentoalveolar morphologic
      features are similar in the present contemporary sample and various
      noncontemporary populations.

PMID- 8290885
TI  - An investigation of some factors associated with occlusal tooth wear in a
      selected high-wear sample.
AB  - The aim of the present study was to investigate the influence of some factors
      associated with occlusal tooth wear in a selected high-wear Swedish sample. The
      material comprised 59 persons having a mean age of 35 yr within the range 16-70
      yr, the criteria for selection being a full or near-full complement of natural
      teeth, and the presence of definite clinical signs of occlusal wear. A dentition
      wear index, in addition to anterior, posterior, and arch subindices, was derived
      from a tooth-by-tooth evaluation of casts. Factors which were found to correlate
      significantly with increased occlusal wear were age, sex, self-perception of
      wear, number of teeth, and general health, as well as a number of variables from
      study-cast analysis. On the basis of the findings, not only is the multifactorial
      etiology of occlusal tooth wear a reality, but so, too, is the complex
      interdependence of these factors in the severity of wear.

PMID- 8290886
TI  - Maximal contraction force and endurance of human jaw-closing muscles in isometric
      clenching.
AB  - Maximal unilateral bite force and endurance times from maximal bite force to the
      75% and 50% levels of maximal values were recorded for 13 men and 15 women with
      bite openings of 10 and 14 mm. Measurements were made both from right and left
      molar regions and from the incisal region. Bite force values were significantly
      higher than previously measured in endurance tests by devices with unilateral
      housings. Men achieved greater bite force than women in the molar region in every
      trial. The general assumption that women's muscles are superior to those of men
      in static endurance when both are working at the same percentage of maximal
      voluntary contraction was not supported by this work for jaw-closing muscles. The
      endurance times to 75% and 50% levels of maximal bite force were shorter than
      could be expected from previous reports, and endurance times to the 50% level
      were even shorter than those reported for muscles of limbs.

PMID- 8290887
TI  - The Nobel Lectures in Immunology. The Nobel Prize for Physiology or Medicine,
      1990. The first successful organ transplants in man.

PMID- 8290888
TI  - A murine monoclonal multireactive immunoglobulin kappa light chain.
AB  - N12.12 is a monoclonal immunoglobulin (Ig) kappa light chain (KLC) secreted by a
      B-cell hybridoma derived from spleen cells of a normal SJA mouse. No heavy chain
      was detected in the culture supernatant of this hybridoma using an enzyme
      immunoassay (EIA) and after polyacrylamide gel electrophoresis (SDS-PAGE) of the
      35S-methionin biosynthetically labelled proteins secreted by the cells. It was
      shown that N12.12 KLC reacted with mouse actin, trinitrophenylated bovine serum
      albumin (TNP25-BSA) and weakly with bovine myoglobin. The binding of the N12.12
      'monoclonal antibody' to mouse actin or to TNP25-BSA was inhibited specifically
      by both antigens with a dissociation constant (KD) for binding to mouse actin of
      10(-7) M. The results indicate that a free KLC can bind both to mouse and to non
      mouse molecules, thus exhibiting binding characteristics usually attributed to
      natural multireactive antibodies.

PMID- 8290889
TI  - Characterization of an early activation-dependent antigen on lymphocytes defined
      by the monoclonal antibody BL-Ac(F2).
AB  - A novel activation-dependent lymphocyte cell-surface antigen which is recognized
      by a MoAb, BL-Ac(F2), is described. Although not found on resting lymphocytes the
      antigen is induced rapidly within 2-4 h following stimulation of the cells using
      mitogens or antibodies against the T-cell CD3 antigen and sIgM on B cells,
      respectively. Immunoprecipitation and Western Blotting indicated that the MoAb
      recognizes a molecule in a range of 78-85 kDa. Beyond its activation-dependent
      expression on lymphocytes the antigen was detected also on myelo-monocytic cells.
      Expression kinetics and cellular distribution of this molecule suggest that it is
      distinct from previously described activation-dependent cell-surface antigens
      such as CD69, CD25 and 4F2.

PMID- 8290890
TI  - Experimental allergic bronchopulmonary aspergillosis in the mouse: immunological
      and histological features.
AB  - C57BL/6 mice treated with intranasal instillation of 100 micrograms of
      Aspergillus antigen three times a week developed a pulmonary eosinophilia,
      observed in the bronchoalveolar lavage (BAL) and on histopathological
      examination. At week 3, the instillation of Aspergillus antigen provoked a 10
      fold increase in the BAL cell number and eosinophils were the predominant
      inflammatory cells (66.4%). Histopathological findings showed focal alveolar
      lesions with peribronchial and perivascular infiltration of lymphoid cells,
      numerous eosinophils, epithelioid cells, and granulomas with giant cells.
      Increases in total IgE and IgG1 levels in BAL fluid (33-fold and 14-fold) and
      serum (67-fold and 8-fold) were observed also (P < 0.05). IgG1 specific to
      Aspergillus fumigatus (Af) was detected only in the antigen-treated mice. At 12
      weeks, there was a persistent but less intense eosinophilia both in BAL and on
      histopathological examination accompanied by steadily elevated total IgE and
      total IgG1 and a higher level of specific IgG1-Af in BAL fluids and sera. No
      bronchocentric granulomatosis, mucoid impaction nor bronchiectasis could be
      observed. Data from the study described here showed that in mice repeated
      exposure to Aspergillus antigen leads to a strong inflammatory pulmonary
      response, characterized by remarkable pulmonary eosinophilia and elevations of
      total IgE, total IgG1 and specific IgG1-Af in both BAL and serum, which are the
      hallmarks of human allergic bronchopulmonary aspergillosis also. However, this
      inflammation did not induce the chronic histological features of the human
      disease.

PMID- 8290891
TI  - Interferon-gamma stimulates neopterin release from cultured kidney epithelial
      cells.
AB  - The ability of cultured kidney epithelial cells (KEC) to secrete neopterin, which
      is a marker of the activation of immune system was studied. In this study
      interferon gamma (IFN-gamma) was shown to induce neopterin release from KEC in a
      dose- and time-dependent manner. Many other cytokines and mitogens (IL-1 beta, IL
      2, IL-6, LPS and phorbol ester) were tested for their ability to induce neopterin
      in KEC but all failed to induce a significant release of neopterin from KEC. By
      itself TNF-alpha induced a release of small amounts of neopterin but strongly
      potentiated the effect of IFN-gamma in a synergistic manner to induce neopterin
      secretion. These data indicate that not only monocytes and macrophages which it
      is well known secrete neopterin, but KEC are responsible also for the high serum
      or urine level of neopterin observed in patients with kidney allograft rejection
      or infections episodes. As the amount of neopterin released by KEC is smaller
      than that secreted by activated macrophages, the contribution of KEC to the
      overall production of neopterin during certain diseases may be small.

PMID- 8290892
TI  - Fc receptors expression and function in mononuclear phagocytes from AIDS
      patients: modulation by IFN-gamma.
AB  - Fc-receptor (FcR)-mediated phagocytosis and FcR (FcRI, FcRII and FcRIII) membrane
      expression was studied on freshly separated and cultured monocytes (Mo) from 20
      AIDS patients and 20 healthy controls. Both Mo and Mo-derived macrophages from
      AIDS patients presented a significant defect in their capacity to ingest IgG
      coated erythrocytes (EA) compared to control cells. This functional defect did
      not depend on a decline in the number of FcR+ cells or on a decrease in the
      expression of FcR on their surface. In fact, the percentages of phagocytes
      reacting with anti-FcRI MoAb (32.2) or anti-FcRII MoAb (IV.3) were similar for
      controls and AIDS patients, while the percentage of FcRIII-positive Mo (MoAb 3G8)
      was higher in the AIDS population than in controls, though this difference was
      not seen on cultured Mo. The level of FcRI expression, evaluated as mean
      fluorescence intensity (MFI), was higher on freshly separated Mo from AIDS
      patients than from controls but this difference disappeared also with
      differentiation of Mo to Mo-derived macrophages in vitro. Parallel analysis of
      FcRII and FcRIII on phagocytes revealed no differences in the MFI between the
      AIDS and control groups. Some observations suggested that this functional defect
      might be secondary to phagocyte priming by circulating IFN-gamma: (1) in vitro
      stimulation of Mo with hrIFN-gamma, which increased FcRI expression, actually
      reduced phagocytosis of IgG-coated particles; and (2) IFN-gamma concentrations
      were increased in AIDS patients' plasma. In spite of these findings, no
      significant correlation was found between plasma IFN-gamma concentrations and FcR
      mediated ingestion in AIDS patients, making the hypothesis uncertain. Even if the
      basis for the impaired FcR-mediated phagocytosis in AIDS patients remains
      unclear, this functional defect may have a role in the immunopathogenesis of
      AIDS, constituting a component cause of the immunodeficiency.

PMID- 8290893
TI  - Endogenous IL-10 and IFN-gamma production controls thymic cell proliferation in
      mice acutely infected by Trypanosoma cruzi.
AB  - Thymocytes from mice with experimental Trypanosoma cruzi infection respond poorly
      to Con-A stimulation. However, the proliferative capacity of these cells is not
      impaired, as demonstrated by the fact that at high doses, exogenous rIL-2
      restores thymidine uptake. This finding could be explained either by insufficient
      IL-2 production or by the appearance of inhibitory factors during T. cruzi
      infection. This paper shows that in response to Con A, IL-2 production is
      decreased in the model. Furthermore, the whole profile of cytokine production is
      modified, with a striking increase in IL-10, IFN-gamma, IL-4, IL-5 and IL-6
      production. The results indicate that IL-10 plus IFN-gamma are responsible for
      the decrease in the Con A-induced proliferation since a normal proliferative
      response as well as normal IL-2 production can be restored if both cytokines are
      neutralized by adding their monoclonal antibodies (MoAbs). Evidence is provided
      also for an enhanced non-specific cytotoxicity of thymic cells from infected mice
      that might involve IL-4, IL-5 and IL-6. This is the first study demonstrating an
      alteration of thymic cell function by T. cruzi infection which results from
      overstimulation of IL-10 and IFN-gamma production.

PMID- 8290894
TI  - The interaction between beta 2-microglobulin (beta 2m) and purified class-I major
      histocompatibility (MHC) antigen.
AB  - The function of MHC class-I molecules is to sample peptides from the
      intracellular environment and present them to CD8+ cytotoxic T lymphocytes. To
      understand the molecular details of the assembly (and disassembly) of peptide
      beta 2m-class-I complexes a biochemical peptide-class-I binding assay has been
      generated recently and this paper reports on a similar assay for the interaction
      between beta 2m and class I. As a model system human beta 2m binding to mouse
      class I was used. The assay is strictly biochemical using purified reagents which
      interact in solution and complex formation is determined by size separation. It
      is specific and highly sensitive. The observed affinity of the interaction, KD,
      is close to 0.4 nM. The rate of association at 37 degrees C is very fast (the ka
      is around 5 x 10(4)/M/s) whereas the dissociation is slow (the kd is around 8 x
      10(-6)/s); the ratio of dissociation to association yields a calculated KD close
      to the observed value. At 37 degrees C almost all of the purified class I
      participates in binding of the exogenously offered beta 2m showing that a
      considerable exchange of the endogenous beta 2m occurs. Finally, it was
      demonstrated that exogenous beta 2m enhances binding to MHC class-I of short
      perfectly-matching peptides as well as longer peptides.

PMID- 8290895
TI  - Target-cell sensitivity to natural killer-cell lysis is determined by the
      expression of a novel antigen in conjunction with major histocompatibility
      complex class-I molecules.
AB  - Recently, a panel of monoclonal antibodies (MoAbs) was developed that identified
      a novel tumour-cell antigen conserved across species (mouse, rat and man).
      Fluorescence-activated cell sorter (FACS) analysis demonstrated that this antigen
      was expressed at highest levels on human tumour cell lines sensitive to natural
      killer (NK)-cell lysis. These MoAbs inhibited NK cell lysis of K562 target cells
      (by up to 90%), as well as a variety of other NK-sensitive target cells.
      Biochemical analyses revealed that the MoAbs reacted with a polypeptide of 42
      kDaltons, distinct from other known cell surface antigens. Now the expression of
      this antigen has been analysed further with a panel of 24 tumour cell lines to
      determine its role in NK cell function. The expression of target cell major
      histocompatibility complex (MHC) molecules in conjunction with sensitivity to NK
      cell lysis was examined also. For each of the 24 cell lines it was found that the
      level of expression of the novel target cell antigen determined the sensitivity
      of the cell line to NK cell lysis. However, the level of MHC antigen expression
      could modulate target cell sensitivity to NK cell lysis, in that high levels of
      MHC class-I molecule expression resulted in a target cell that was insensitive to
      NK cell lysis regardless of the level of expression of the novel antigen. Thus,
      for most transformed cell lines, sensitivity to NK cell lysis appeared to be
      determined by the expression and levels of the novel antigen in association with
      MHC class-I molecules.

PMID- 8290896
TI  - Global analysis of antibody repertoires. 1. An immunoblot method for the
      quantitative screening of a large number of reactivities.
AB  - This paper describes a procedure for analysing multiple antibody reactivities
      that explores a commercially available immunoblot system, and is based on a
      double staining of nitrocellulose membranes, revealing both antibody reactivities
      and the migration position of the blotted proteins in the membrane.
      Quantification of both stainings by densitometry allowed the accurate
      superposition of the immunoreactivity and total protein profiles of each lane.
      Moreover, the protein stainings of the different lanes could be adjusted with a
      simple-scale transformation algorithm, correcting for possible distortions during
      electrophoretic migration, and allowing for the precise comparison of the
      immunoreactivity profiles in different lanes. The procedure is discriminatory
      enough to identify unique reactivity patterns in random pools of 10(4) activated
      B cells, and to define strain-specific natural antibody repertoires. The utility
      of this immunoblot method as an assay for simultaneously scoring multiple
      reactivities to hundreds of antigens in complex mixtures of antibodies, and thus
      defining antibody repertoires in a global manner, is discussed.

PMID- 8290897
TI  - The primary structure of serum amyloid A protein in the sheep: comparison with
      serum amyloid A in other species.
AB  - Serum amyloid A (SAA) protein was isolated from acute phase sheep sera by
      ultracentrifugation, gel filtration and ion-exchange chromatography. The purified
      protein was characterized by sodium dodecylsulfate polyacrylamide gel
      electrophoresis (SDS-PAGE), isoelectric focusing, amino acid composition and
      Edman degradation. Protein SAA sheep consists of 112 amino acid residues and has
      a blocked N-terminus. The amino acid sequence showed a high degree of homology
      with SAA proteins from other species, especially at positions 32 to 54,
      indicating that this particular part of the protein is important for its
      function. When compared to human protein SAA, nine inserted amino acids could be
      demonstrated, located in regions 69 to 77. Similar observations have been seen in
      cow, horse, dog, cat, and mink protein SAA. Heterogeneities were found in
      positions 28, 55, 63, 64, 66, 75, 77, 78, 80 and 89. Positions 63, 64, 66, 75,
      77, 78 and 80 revealed the existence of a minor gene product of protein SAA
      sheep. The minor variant of protein SAA sheep is identical in these positions
      with the corresponding positions in protein SAA cow. By comparing the amino acid
      sequences of the different SAA proteins, two separate branches in the
      evolutionary pattern of protein SAA appear. One of the branches includes the
      species with the insertion which represents also one of the more heterogeneous
      part of the protein.

PMID- 8290898
TI  - Utilization of a potentially universal downstream primer in the rapid
      identification and characterization of V lambda genes from two new human V lambda
      gene families.
AB  - Polymerase chain reaction (PCR) has increased dramatically the speed of cloning
      and characterizing numerous genes. However, its application to identifying and
      analysing new germline Ig-variable (V) gene families has been hampered by the
      lack of sequence information in the downstream flanking regions of the concerned
      V genes, which are deleted during V(D)J rearrangements. To circumvent this
      problem, the possibility was explored that a degenerate downstream primer may be
      used in conjunction with a specific upstream primer, to clone members of new V
      lambda gene families, as much less is known about V lambda genes than Vh and Vk
      genes in humans. Firstly the feasibility and the specificity of a degenerate
      primer was examined by comparing it with an established downstream primer in
      amplifying known V lambda 1 genes. The results were positive. Thus, the
      degenerate primer was used to clone and characterize germline V lambda genes of
      the recently defined V lambda 8 and V lambda 9 gene families. This current
      strategy may help speed up the identification and characterization of all human V
      lambda genes. Moreover, a similar strategy can be applied to identify and
      characterize rapidly new V genes of either known or unknown Ig and T-cell
      receptor V gene families.

PMID- 8290899
TI  - Epidemiology and sensitivity of 8625 ICU and hematology/oncology bacterial
      isolates in Europe. International Study Group.
AB  - A multicenter in-vitro study was conducted in 13 countries between May and
      November, 1992 to determine both the current bacterial epidemiology in Intensive
      Care and Hematology/Oncology units and the susceptibility of the organisms to
      cefpirome and other commonly used antibacterials. Eighty-nine hospitals each
      collected 100 consecutive nonduplicate aerobic clinical isolates from patients in
      either an Intensive Care (81%) or Hematology/Oncology (19%) unit. The major
      sources of isolates were respiratory, skin/wound, blood and urine. The MIC of
      eight different antibiotics was determined using a custom microdilution plate.
      Predominant bacteria accounting for 80% of the 8625 isolates included:
      staphylococci (26%); Escherichia coli (17%); Pseudomonas aeruginosa (12%);
      Klebsiella spp. (10%); Enterobacter spp. (8%) and enterococci (7%). Gram-positive
      isolates accounted for more than 35% of all isolates. Based on the susceptibility
      results to the predominant pathogens, the activity of the drugs tested could be
      categorized into three groups. Cefpirome and imipenem had the most potent in
      vitro activity, followed by the third generation cephalosporins cefotaxime,
      ceftazidime and ceftriaxone, and then piperacillin. The large percentage of Gram
      positive bacterial isolates in this patient population indicates the utility of
      antimicrobial agents that are equally effective against both Gram-positive and
      Gram-negative organisms.

PMID- 8290900
TI  - Cross-susceptibility of cefpirome and four other beta-lactams against isolates
      from haematology/oncology and intensive care units. International Study Group.
AB  - A multi-centre in-vitro study (8625 isolates) was conducted in 13 countries
      between May and November, 1992 to determine both the current bacterial
      epidemiology in intensive care and haematology/oncology units and the cross
      susceptibility of the organisms to cefpirome, ceftazidime, ceftriaxone, imipenem
      and piperacillin. Bacterial species with 20 or more isolates resistant to one of
      the six antibiotics were examined for their susceptibility to the beta-lactams.
      Cefpirome and imipenem had the smallest total numbers of isolates. Bacteria
      resistant to ceftazidime or ceftriaxone were often susceptible (> 50%) to
      cefpirome. Conversely, cefpirome resistant isolates were frequently resistant (>
      90%) to ceftazidime and ceftriaxone. P. aeruginosa was an exception, exhibiting
      cross-resistance to all cephalosporins. beta-lactamase producing Enterobacter,
      Citrobacter and Klebsiella spp. were especially resistant to piperacillin and
      ceftazidime but not cefpirome or imipenem. Two-thirds or more of coagulase
      negative staphylococci resistant to any single agent, including imipenem,
      maintained their susceptibility to cefpirome. Cross-class resistance was not
      exhibited by imipenem and cefpirome against ciprofloxacin resistant isolates but
      was more evident for piperacillin, ceftazidime and ceftriaxone. Cefpirome was
      more active than ceftazidime against bacteria resistant to both piperacillin and
      gentamicin, especially coagulase-negative staphylococci (76% vs. 6%) and
      Enterobacter spp. (56% vs. 21%). Many coagulase-negative staphylococci and
      Enterobacter spp. susceptible to cefpirome (50-89%). These results suggest that
      cefpirome has a potential clinical advantage against gram-positive and gram
      negative bacteria resistant to other beta-lactams, including imipenem.

PMID- 8290901
TI  - The pharmacokinetics of cefpirome--rationale for a twelve-hour dosing regimen.
AB  - Cefpirome is a new broad-spectrum beta-lactam antibiotic that exhibits minimal
      concentration dependent killing and produces prolonged postantibiotic effects
      only with Staphylococcus aureus. These pharmacodynamic characteristics suggest
      that the goal of optimal dosing regimens for cefpirome is to provide serum levels
      above the MIC of infecting pathogens for most of the dosing interval. Cefpirome
      has a half-life of 2.0 hours in normal volunteers that increases to 3.1 to 4.4
      hours in elderly patients. Serum concentrations following 0.5, 1.0 and 2.0 grams
      of cefpirome are above the MIC of common pathogens for more than half of the
      dosing interval. For many of the Enterobacteriaceae, serum concentrations are
      above the MIC for over 12 hours. The drug distributes primarily into
      extracellular fluid and does provide potentially therapeutic concentrations in
      cerebrospinal fluid (CSF). The drug is eliminated primarily by the kidney and
      requires dosage modification when the creatinine clearance is below 50 ml/min.
      The half-life of the drug is not significantly altered in patients with cystic
      fibrosis and hepatic dysfunction. The integration of the drug's pharmacokinetic
      and pharmacodynamic characteristics support the use of a 12-hour dosing interval
      for the treatment of serious infection.

PMID- 8290902
TI  - Cefpirome: efficacy in the treatment of urinary and respiratory tract infections
      and safety profile.
AB  - The efficacy and safety of cefpirome was reviewed from the documentation of
      comparative pivotal trials in patients with urinary tract or lower respiratory
      tract infections UTIs and LRTIs, respectively). A majority of patients with UTIs
      had pyelonephritis and/or complicated UTIs. Most patients with LRTIs had
      community acquired pneumonia. Studies of UTI included 865 patients treated with
      cefpirome 1 g bid and 443 patients allocated to ceftazidime 1 g bid. Satisfactory
      clinical outcome was reported in 87% and 83%, respectively. Eradication of
      organisms causing bacteriuria was achieved in 87% and 86%, respectively. In the
      LRTI trials 199 patients received cefpirome 1 g bid and in 653 patients it was
      dosed 2 g bid. Comparators were ceftazidime 2 g bid (N = 197) or 2 g tid (N =
      296) or ceftriaxone 1 g bid (N = 77). With all treatments unsatisfactory clinical
      or bacteriological outcome was recorded in < 15% of the patients. The safety of
      cefpirome and comparators was evaluated in pivotal phase II and III studies and
      deaths were analysed in all clinical trials for which data were available by June
      30th 1991. Cefpirome did not differ from comparators in terms of frequencies or
      distribution within body systems of adverse events. Death rates were 3.9% in 9189
      patients receiving cefpirome and 5.1% in 3162 receiving a comparator. The deaths
      were in an absolute majority of cases not considered related to study drug given.
      The most common cause of death was infection, indicating that the trial samples
      were selected from populations of patients with serious infections. Cefpirome was
      as safe and efficaceous as its comparators and is a new injectable cephalosporin
      with broader spectrum than ceftazidime. It should be a suitable alternative for
      empiric treatment of serious infections in hospitalised patients.

PMID- 8290903
TI  - Efficacy of cefpirome in the treatment of septicaemia.
AB  - From a total of 4180 patients entered in 15 phase II-III clinical trials
      involving cefpirome, an analysis was carried out on 378 patients with
      bacteriologically confirmed or suspected septicaemia who were treated with
      cefpirome (n = 282) or comparator drugs (ceftazidime, n = 80; ceftriaxone, n =
      15; imipenem/cilastatin, n = 1). Gram-negative organisms were the causative
      pathogens in over half of the patients, with Escherichia coli being the most
      common species found. The most frequently isolated Gram-positive bacterium was
      Streptococcus pneumoniae. Causative organisms were eradicated in over 90% of
      patients receiving cefpirome or comparators. Only 4/230 pathogens tested were
      resistant to cefpirome in vitro. Among patients with bacteriologically confirmed
      septicaemia, a satisfactory clinical response was documented in 131/176 (74%)
      cefpirome vs 34/50 (68%) ceftazidime vs 5/10 (50%) ceftriaxone recipients,
      improvement in 39/176 (22%) vs 11/50 (22%) vs 5/10 (50%), and failure in 6/176
      (4%) vs 5/50 (10%) vs 0/10 (0%), respectively. Similar results were achieved in
      patients with 'suspected' septicaemia. Cefpirome 1 or 2 g twice daily offers an
      effective treatment option for patients with septicaemia. The higher dosage
      regimen produced superior bacteriological clearance rates and is therefore
      preferable in patients with severe septicaemia.

PMID- 8290904
TI  - Infection problems for the 1990's--do we have an answer?
AB  - There is and has been continued change in organisms causing infection in the
      hospital. In the past few years, although Gram-negative bacteria have remained a
      major cause of mortality, Gram-positive bacteria and fungi have become
      increasingly important. This has caused organisms such as methicillin-resistant
      staphylococci, enterococci, Xanthomonas maltophilia and multiply resistant
      Pseudomonas aeruginosa to be common pathogens. Can this difficult state of
      affairs be changed by better antimicrobial prescribing practices? Yes and no.
      Virtually any agent will select MRSA and MRSE since the chromosomal location of
      the resistance of multiple-antibiotics makes such selection common and explains
      the rapid rate of the fluoroquinolones as therapy of MRSA. Restriction of oral
      vancomycin will markedly reduce the pressure to select Enterococcus faecium and
      thus limit the spread of the organisms and delay transmission of glycopeptide
      resistance to S. aureus. Judicious use of antibiotics in the intensive care
      environment will be major factor in "saving" antibiotics for other patients since
      the ICU patient goes to other parts of the hospital carrying with him/her the
      baggage of resistant Staphylococcus haemolyticus, klebsiella, P. aeruginosa,
      acinetobacter, enterobacter, xanthomonas and Pseudomonas cepacia. All of these
      organisms have the potential to become resistant to the agents heretofore used to
      treat them and are common in ICU patients.

PMID- 8290905
TI  - Individualized use of hemodialysis and peritoneal dialysis.
AB  - Over the past few years it has better been realized how individual the needs for
      the effectiveness ("dose") of dialytic therapy are and which treatment related
      factors affect the morbidity and mortality of dialysis patients. Although the
      role of urea, a marker of small molecular weight uremic toxins, has been
      challenged, most studies have been based on kinetics of urea during and between
      dialyses. The dose of dialysis affects also the nutritional status and a special
      role for "middle" molecules as anorectic factors has been suggested. This article
      gives an in-depth view of some factors which affect the needs for the
      effectiveness of dialytic therapy, a summary of the goals of the treatment, and
      some practical guidelines how to reach them.

PMID- 8290906
TI  - The distribution of 3H-labeled endotoxin in the kidney of liver cirrhotic rats.
AB  - Although the etiology and pathogenesis of progressive renal failure is largely
      unknown, endotoxin is supposed to be one of the contributory factors. However,
      the distribution of endotoxin in liver cirrhosis has not been clarified.
      Therefore we studied the distribution of 3H-labeled endotoxin in the kidney in
      rats with CCl4-induced liver injury. Daily inhalations of CCl4 on rats for 6 and
      10 weeks produced liver fibrosis (LF group, N = 5) and cirrhosis (LC group, N =
      5), respectively. At 6 or 10 weeks, animals were sacrificed 24 hours after an
      intravenous injection of endotoxin labeled with 3H at the galactose moiety
      (12,000 cpm/1 g body weight). In the liver, 3H-labeled endotoxin was taken up
      mainly by Kupffer cells as determined by autoradiography. Compared to control
      rats, in rats of the LC or LF group the measured amount of 3H-labeled endotoxin
      per gram kidney or ml blood increased, while that of the liver was significantly
      decreased. A positive correlation of the amount of 3H-labeled endotoxin per
      weight or volume respectively was shown between kidney and blood, but not between
      lung or spleen and blood. These results suggest that overflow of endotoxin due to
      decreased inactivation in the liver causes endotoxemia in liver injury and that
      the resulting endotoxemia may directly affect the kidney. The resulting endotoxin
      induced vasoconstriction may be a contributory factor for the progressive renal
      failure frequently observed in liver cirrhosis.

PMID- 8290907
TI  - Involvement of the renin angiotensin system in the pathogenesis of postexercise
      proteinuria.
AB  - Proteinuria after strenuous exercise is common in healthy subjects. The
      pathophysiologic mechanism of postexercise proteinuria (PEP) is not clear,
      although the phenomenon has long been known and many explanatory theories have
      been proposed. It is widely recognized that angiotensin II may increase
      filtration of protein through the glomerular membrane, and that its concentration
      in plasma increases during exercise. The aim of this study was to evaluate
      possible involvement of angiotensin II in the pathogenesis of PEP. Of 25 young
      volunteers who performed maximal aerobic exercise, eight showed PEP. The exercise
      was repeated after an interval of at least one week, now 90 minutes after
      administration of captopril (25 mg). Captopril did not affect the achieved work
      load of the maximal blood pressure and heart rate during the exercise, but PEP
      was not found. As it was possible to prevent PEP by administering an angiotensin
      converting enzyme inhibitor, the study supports the theory that the renin
      angiotensin system is involved in the pathogenesis of PEP.

PMID- 8290909
TI  - Percutaneous extraction of upper urinary calculi under fluoroscopic control-
      still a valuable complement to ESWL.
AB  - Percutaneous extraction of 372 renal and proximal ureteral calculi was performed
      under fluoroscopic control in 202 consecutive patients. In 193 kidneys (90%)
      removal of stones was performed under fluoroscopic control only and in 10%
      initial ultrasonic disintegration was used. A completely stone free kidney was
      achieved in 74%. If successful outcome is defined as no stones or residual
      fragments less than 5 mm, the success rate was 91%. With a mean size of 10.3 mm
      259 intact stones were extracted under fluoroscopic control. Open surgery was
      performed in 13 of 202 patients, in 10 of these cases due to unsuccessful removal
      of an impacted ureteral stone. Complications occurred in 16%, none of them were
      serious. Open intervention became necessary in 2 patients. Bleeding which
      required blood transfusion occurred once. Percutaneous renal stone extraction
      under fluoroscopy is safe and useful in selected patients when ESWL can be
      expected to produce less favourable results. The ability to perform this
      technique should therefore be well maintained.

PMID- 8290908
TI  - The reliability and representativity of non-dynamic bone histomorphometry in
      uremic osteodystrophy.
AB  - In order to evaluate the reliability and representativity of iliac crest bone
      biopsy in uremic osteodystrophy, non-dynamic bone histomorphometry was performed
      post-mortem on the right and left iliac crests and the 3rd lumbar vertebra in 20
      patients with chronic uremia. High (> 0.8) right-left correlation coefficients
      were found for bone volume, osteoid volume, osteoid surface, osteoid thickness,
      eroded surface, osteoclast surface and aluminium labelling intensity; moderate
      (0.7-0.8) for trabecular thickness, and low (< 0.7) for cortical thickness,
      porosity and aluminium bone concentration. High iliac crest-vertebra correlations
      were found for trabecular thickness, osteoid volume, osteoid surface, eroded
      surface, osteoclast surface and aluminium labelling intensity, and low
      correlations for bone volume, osteoid thickness and bone aluminium concentration.
      In conclusion, non-dynamic iliac trabecular bone indices are reliable variables
      and, with the possible exception of bone mass determination, indicative of
      systemic bone disease. Bone aluminium concentration and cortical bone indices are
      unreliable measures of uremic bone disease. These reservations apply to the
      diagnostic use of biopsy in individuals, but not necessarily its research use in
      groups of patients.

PMID- 8290910
TI  - Analgesic effect and tolerance of ketoprofen and diclofenac in acute ureteral
      colic.
AB  - Eighty-six patients with ureteral colic were included in a randomised,
      prospective, double-blind study of the analgesic efficacy and tolerance of
      ketoprofen versus diclofenac, both administered intramuscularly. There were no
      significant differences regarding pain-relief or side-effects.

PMID- 8290911
TI  - Trends in the incidence of cancer of the kidney, pelvis, ureter and bladder in
      Denmark 1943-88.
AB  - Temporal trends in the incidence of cancer of the renal parenchyma, renal pelvis,
      ureter, bladder, urethra and Wilm's tumor in the period 1943-88 were described.
      Log-linear Poisson models were used to estimate the changes over time and the
      geographical variations. We have found a steep increase in the incidence of
      pelvis and ureter cancer; and to some extent also for bladder cancer in men. The
      incidence of cancer of the renal parenchyma has increased more moderately while
      the rates of Wilm's tumor have been virtually stable throughout the period. These
      findings suggest that tumors in the urinary system differ with respect to risk
      factors and should be grouped by their histological origin as well as
      topographical site.

PMID- 8290912
TI  - Spontaneous peripelvic extravasation of urine as a cause of acute abdomen.
AB  - In eight patients with sudden onset of flank pain, urography showed extravasation
      of urine. The cause of peripelvic leakage was verified ureteral stone in four
      cases, stricture of the ureteropelvic junction in one, and unknown in three
      cases. Treatment was symptomatic in four cases, drainage in two and surgery in
      two cases. Seven patients recovered uneventfully, but one required nephrectomy.
      The prognosis in spontaneous urinary extravasation is usually good without
      drainage. Open surgery is seldom indicated.

PMID- 8290913
TI  - The structure of large lamellar urinary stones. A quantitative chemical analytic
      study applying a new classification scheme.
AB  - To study the structural composition of 61 renal and 9 vesical large lamellated
      non-infection urinary tract stones, samples from successive layers were
      quantitatively analyzed with standard chemical techniques, but with a new
      classification based on percentage composition of ions rather than compounds. The
      commonest pattern of composition (n = 41) was that of the lamellar stones of one
      stone type (uric acid, oxalate, or phosphate) and group (according to % of
      indicating ion), followed by bilamellar stones of different stone types (17) or
      of one stone type but different groups (8). The other stones were trilamellar (3)
      or quadrilamellar (1) of different stone types. In the 29 stones with lamellae of
      different type and/or group, the chemical composition of successive layers seemed
      to confirm the correlation between uric acid and oxalate, rather than phosphate,
      ions and between oxalate and both uric acid and phosphate ions. An influence on
      these correlations either positive or negative, may be the responsible factor for
      specifying the type and group of a forming stone or layer of a stone. The
      observed ionic correlations within the stones seem to support the choice of the
      oxalate ion, in the uric acid or phosphate stones, and both of the uric acid and
      phosphate ions, in the oxalate stones, as indicating ions for grouping in our
      proposed classification of urinary stones.

PMID- 8290914
TI  - Relationship between blood groups and tumour grade, number, size, stage,
      recurrence and survival in patients with transitional cell carcinoma of the
      bladder.
AB  - Blood group was correlated with the tumour grade, number, size, stage and
      recurrence rate and with survival in 261 consecutive patients with bladder cancer
      analyzed at least five years after diagnosis of the disease. The distribution of
      blood groups did not differ from that in the general population. There were no
      significant differences in the incidence of invasion at the time of diagnosis or
      later, in the number of the tumours or in the recurrence rate. A tendency for
      high-grade and large-sized tumours was observed in the blood groups O(H) and B.
      Differences in mortality were not observed until eight years after diagnosis, so
      that 28% of the patients with blood group A and 40% of those with blood group O
      had died of bladder cancer by ten years after diagnosis. Since the differences
      are small, the clinical significance of blood groups as a prognostic factor in
      bladder cancer patients is minimal. However, there seems to be a need for further
      research of the significance of genetic background in the natural history of
      bladder cancer.

PMID- 8290915
TI  - The reliability of staging and grading of bladder tumours. Impact of
      misinformation on the pathologist's diagnosis.
AB  - The influence of misinformation on the reliability of the histopathological
      classification of bladder tumours was analysed. Four consultant pathologists
      assessed 40 biopsy specimens of bladder tumours staging invasion and grading the
      specimens according to the Bergkvist classification. A random sample of 20
      specimens was accompanied by systematically distorted information ("bias"-unknown
      to the pathologists) about previous histological grading of the patient (bias
      group); the other 20 specimens were used as control group (non bias group). After
      6 months a second round with the same specimens was arranged to assess the
      influence of bias on the intraobserver variation. Using kappa (kappa) statistics
      the chance corrected interobserver agreement rate was poor both in staging of
      invasion and grading according to the Bergkvist classification (kappa < 0.50).
      The kappa values in the intraobserver study ranged from poor to excellent with a
      tendency towards lower kappa when the observer had been biased. The kappa values
      in the assessment of malignancy were acceptable to excellent. False information
      did not affect the pathologists' diagnosis significantly.

PMID- 8290916
TI  - Neoadjuvant chemotherapy in bladder cancer: a randomized study. Nordic Cystectomy
      Trial I.
AB  - An analysis by the Nordic Cooperative Bladder Cancer Study Group concerned the
      possible benefit of neoadjuvant chemotherapy--given before scheduled low-dose
      irradiation and cystectomy. In the trial, started in 1985, 311 patients with
      locally advanced bladder cancer, T1 grade 3, T2-T4a NXMO, were randomly allocated
      to a 'chemotherapy' or a 'no chemotherapy' group. Chemotherapy consisted of two
      cycles comprising cisplatin 70 mg/m2 and doxorubicin 30 mg/m2, with a 3-week
      interval between cycles 1 and 2. All patients were locally irradiated with 4 Gy
      daily for 5 consecutive days. The follow-up included 266 cystectomized patients.
      In May 1992 the mean observation time was 18 months for all patients and 47
      months for those still alive. The results suggest that a significant downstaging
      in the group randomized to chemotherapy was found only in T1, grade 3 tumours (56
      patients, p = 0.002). The overall survival rate in all 311 patients was
      significantly higher in the chemotherapy group (p = 0.03) and likewise among the
      253 patients with T2-T4a tumour (p = 0.018). For the 210 patients who underwent
      cystectomy for T2-T4a tumour, there was a trend towards longer survival when
      chemotherapy was given (p = 0.057). Patients with initially muscle-invasive
      tumour who responded to neoadjuvant treatment survived longer than non responders
      (p = 0.0005). The results suggest that neoadjuvant chemotherapy improve the
      outcome of radical surgery for muscle-invasive bladder cancer, though the effect
      on long-term survival is inconclusive. Further studies on the effect of
      neoadjuvant chemotherapy is initiated.

PMID- 8290917
TI  - Time lag to diagnosis of bladder cancer--influence of psychosocial parameters and
      level of health-care provision.
AB  - Delay in diagnosis of carcinoma of the urinary bladder was studied in 343
      patients. The median patient's delay (time from first symptom to first
      consultation) was 15 days, and was longer when the only presenting symptom was
      urgency of micturition than when it was haematuria (45 vs. 5 days, p < 0.001). In
      advanced (T2-T4) tumour, patient's delay was 21 days and in Ta-T1 it was 13 days
      (NS). The median doctor's delay (time from first consultation to diagnosis) was
      62 days. It comprised two phases: A from consultation to first referral and B
      from first referral to diagnosis-respective medians 6 and 47 days. Median
      doctor's delay (A+B) was longer when the initial consultation was with a general
      practitioner than with a urologist (78 vs. 21 days, p < 0.001) and longer in
      patients older than 70 years (69 vs. 54 days, p < 0.01). Doctor's delay
      correlated with symptoms, being longest in cases with only urgency and shortest
      in haematuria plus pain (114 vs. 44 days, p < 0.001), and also with number of
      referrals (33, 63, 230 and 117 days, respectively, for 0, 1, 2 and 3 referrals).
      More women than men were referred a second or third time (25.6% vs. 8.6%, p <
      0.001), and doctor's delay was longer for women (76 vs. 59 days, p < 0.05). A
      questionnaire completed by 203 of the 229 surviving patients revealed no
      significant correlation between psychosocioeconomic factors and patient's delay.

PMID- 8290918
TI  - A view on the anatomy of the ureterovesical junction.
AB  - Macro- and microscopic dissection of 8 adult and 2 fetal human bladders was
      undertaken in two directions as part of a study to evaluate ureterovesical
      junction function. In the trigonal region the detrusor muscle consists of 3, more
      or less triangular layers. Both ureters are only loosely enveloped by a
      fibromuscular sheath of mainly bladder origin. This design allows for easy
      movement of the ureters on their oblique course through the bladder wall. The
      ureteral muscle fibers play only a minor part in the sheath or join the detrusor
      muscle. The majority fan out to end at the bladder mucosa or intermingle with
      fibers originating from the opposite ureter. Since an intricate muscular
      structure can be demonstrated, an active anti-reflux muscular component in the
      normal human bladder seems plausible. A classic ureteral sphincter mechanism does
      not exist. Our findings are discussed and compared with data from the literature.

PMID- 8290919
TI  - Transurethral resection syndrome from extravascular absorption of irrigating
      fluid.
AB  - An analysis was made of the clinical course of 20 transurethral resections of the
      prostate performed under epidural analgesia in which between 676 and 3,600 ml of
      irrigating fluid containing glycine had been absorbed by the extravascular route.
      Symptoms consisted in arterial hypotension (n = 14), postoperative oliguria (n =
      11), nausea (n = 10), bradycardia (n = 7), abdominal discomfort (n = 5) and
      visual disturbances (n = 2). There was a significant correlation between
      hypotension and postoperative oliguria. The hyponatraemia at the end of the
      operation was only one third of the values obtained if the same amount of
      irrigating fluid had been absorbed by the intravascular route. Suprapubic
      drainage of the absorbed fluid (n = 8) did not reduce the hyponatraemia and
      prolonged the postoperative stay in hospital. Diuretics is an alternative to
      surgical drainage in all but the most severe cases of extravasation, but should
      be postponed until normovolaemia is restored and the circulation is stable.

PMID- 8290920
TI  - Asymptomatic varicocele testis.
AB  - The incidence of asymptomatic varicocele among 542 unselected military conscripts
      in Denmark was 9%. Semen from 39 of the 49 men with varicocele was compared with
      findings in age-matched, varicocele-free controls. The overall quality of the
      semen was reduced in the varicocele group (p < 0.001), with significantly lower
      parameters of sperm concentration, total sperm count, qualitative motility and
      sperm motility after 24 hours. There was also significant difference in
      morphology, with more amorphous spermatozoa and more with tail defects (p < 0.05)
      in the varicocele group. The study indicated an association between asymptomatic
      varicocele and compromised sperm quality. The advisability of surgical treatment
      was not clarified, but the two groups of men will be further observed with
      special regard to this question.

PMID- 8290921
TI  - Morphodynamic assessment of penile circulation in impotent patients: the role of
      duplex and color Doppler sonography.
AB  - Duplex and color Doppler sonography were used to assess the vascular status of
      240 impotent patients. The tests were performed before and after intracorporal
      injection of a standard dose of a vasoactive mixture and measurements were done
      both at the crura and at the midshaft of the penis. Particular care was taken in
      the evaluation of cavernosal arteries diameter, wall pulsatility, morphology of
      spectral waveform, blood flow acceleration, systolic and diastolic flow velocity
      and flow volume. Resistance and pulsatility indexes of the cavernosal arteries
      were also measured. Flow along the deep dorsal vein was quantified when possible.
      Cavernosal artery peak systolic flow velocity, flow volume and acceleration were
      the best indicators of arterial penile circulation. Persistently elevated (> 10
      cm/s) diastolic flow in the cavernosal arteries positively correlated with a
      diagnosis of venogenic impotence obtained by dynamic infusion cavernosometry-
      cavernosography in almost 80% of cases. Duplex and color Doppler sonography
      permit to thoroughly evaluate cavernosal arteries function and seem to have a
      promising role in the study of the veno-occlusive mechanism of the corpora
      cavernosa.

PMID- 8290922
TI  - A 6 kg retroperitoneal liposarcoma in a 42-year-old woman. Case report.
AB  - A large retroperitoneal liposarcoma (6 kg) is described in a 42-year-old woman.
      Retroperitoneal tumours are rare, produce nonspecific symptoms, and are often
      extensive when diagnosed. The main treatment of these tumours is radical
      excision, but the tendency to local recurrence makes the prognosis poor.

PMID- 8290923
TI  - Bilateral renal autotransplantation with direct pyelocystostomy in a patient with
      frequent disabling nephroureterolithiasis. Case report.
AB  - A case with disabling nephroureterolithiasis, initially most frequent from the
      right side, later also from the left kidney, is presented. Conservative treatment
      did not improve the condition and bilateral renal autotransplantation with
      pyelocystostomies was performed. Follow-up so far has been uneventful. In highly
      selected cases this is a useful alternative treatment.

PMID- 8290924
TI  - Treatment of cystine stones: combined approach using open pyelolithotomy,
      percutaneous pyelolithotripsy, extracorporeal shock wave lithotripsy and
      chemolysis.
AB  - Treatment of cystine stones in the urinary tract can be difficult because of a
      high frequency of recurrence, resistance to Extracorporeal Shock Wave Lithotripsy
      (ESWL), difficulty in localization and access to peripheral stones during
      Percutaneous Nephrolithotripsy (PCNL), and the insufficient effect of oral
      chemolysis. We present two cases of urinary cystine calculi treated with a
      combination of pyelolithotomy, PCNL, ESWL and percutaneous irrigation chemolysis,
      using N-acetylcysteine and Tromethamine-E.

PMID- 8290925
TI  - Bilateral hydronephrosis with urosepsis due to neglected pessary. Case report.
AB  - In an 86-year-old woman a neglected pessary and extreme coprostasis gave rise to
      anuria, urosepsis and bilateral ureteropelvic dilatation with an empty bladder.
      This seems to be the first reported case of its kind.

PMID- 8290926
TI  - Interposition of ileum in the ureter.
AB  - An ileal loop was interposed to replace a long defect of the upper ureter with
      preservation of the lower ureteral continuity in three patients. Urinary drainage
      was satisfactory and at follow-up 2-4 years postoperatively renal function was
      improved.

PMID- 8290927
TI  - Male genitourinary tuberculosis. Report of 12 cases and review of the literature.
AB  - The incidence of genitourinary tuberculosis is constant in western countries,
      despite dramatically falling prevalence of pulmonary tuberculosis. The kidney is
      especially involved in urinary tuberculosis, and genital tuberculosis mostly
      affects the epididymis in males and the fallopian tubes in females. Twelve cases
      of male genitourinary tuberculosis are presented and the literature is briefly
      reviewed.

PMID- 8290928
TI  - Simultaneous occurrence of carcinosarcoma of the bladder and seminoma of the
      testis. Case report.
AB  - Carcinosarcoma of the bladder is a rare neoplasm composed of both epithelial and
      mesenchymal components. We report on a 51-year-old man with vesical
      carcinosarcoma and seminoma of the testis occurring synchronously.

PMID- 8290929
TI  - [Blood glucose monitoring and late complications of diabetes--consequences of the
      Diabetes Control and Complications Trial (DCCT)].

PMID- 8290930
TI  - [Popliteal aneurysm].
AB  - At our institution operative repair was undertaken for 67 popliteal aneurysms in
      45 patients between 1986 and 1991. In 24 cases emergency surgery was necessary:
      acute critical ischemia due to thrombosis or embolism in 22 cases, and rupture of
      the aneurysm in 2 cases. Two patients died within the first 30 postoperative
      days. Four major amputations could not be avoided. On the other hand, elective
      surgical intervention was possible in 43 cases without operative morbidity and
      mortality. Given the high incidence of serious complications such as thrombosis
      or embolism in popliteal aneurysms, and the reduced success rate of surgery in
      acute critical ischemia, surgical correction upon diagnosis is especially
      recommended in aneurysms with intraluminal thrombus.

PMID- 8290931
TI  - [Acyclovir-resistant Herpes simplex viruses in HIV-infected patients].

PMID- 8290932
TI  - [Late pericardial tamponade: a dangerous complication of postoperative
      anticoagulation following heart surgery].
AB  - Late cardiac tamponade is a condition that presents with subtle signs and
      symptoms within days or weeks after cardiac surgery. During a one-year period, 16
      patients, operated in our institution, developed this complication, mostly due to
      overdosage of anticoagulants. Diagnosis can be difficult and is best confirmed by
      echocardiography. The incidence of this dangerous complication is reportedly
      between 0.3 and 1%. The treatment consists in sub-xyphoid drainage when ever
      possible. In case of loculated or posterior tamponade, re-sternotomy might be
      necessary to assume complete decompression of the heart.

PMID- 8290933
TI  - [Chronic vitamin A poisoning with musculoskeletal symptoms and morphological
      changes of the liver: a case report].
AB  - The case of a 69-year-old woman with a chronic vitamin A intoxication syndrome
      after self-administration of vitamin A is presented. The clinical picture
      included musculoskeletal disorders, headache and hepatomegaly. The diagnosis of
      chronic vitamin A intoxication was based on a history of excessive vitamin A
      ingestion, clinical chemistry and needle biopsy of the liver. Besides retinol and
      retinyl ester, the serum concentration of retinol-binding protein (RBP) should be
      determined. Whereas the serum retinol concentration in chronic vitamin A
      intoxication often does not correlate with toxicity, the ratio between retinol
      and RBP and the concentration of retinyl ester is more sensitive. Morphological
      alterations are associated with the cumulative dosage of ingested vitamin A,
      whereas the daily amount of vitamin A determines the latency until pathological
      changes occur. The hormone-like, retinoid-receptor mediated molecular mechanism
      of action seems to be responsible for the multisystemic manifestations in chronic
      vitamin A intoxication syndrome.

PMID- 8290935
TI  - Human haematopoietic progenitors as a target for gene therapy.

PMID- 8290934
TI  - [Are infant resistant to carbon monoxide poisoning?].
AB  - A 20 year old woman and her 13 weeks old infant were found in the same place
      close together in a house fire. As soon as possible, on-the-spot treatment was
      initiated simultaneously for both victims, i.e. oxygen (100% FIO2), using
      endotracheal intubation and mechanical ventilation for the mother, with
      hyperbaric oxygen when in the hospital, and by facial mask for the baby. On
      admission (35 minutes after discovery in the fire), the mother remained comatose,
      whereas the baby showed only moderate neurologic abnormalities. The initial
      laboratory assessment showed a pH of 7.12 for the mother and 7.06 for the baby.

PMID- 8290936
TI  - A physician's approach to vasospasm.

PMID- 8290937
TI  - Computerised tomography and stroke.
AB  - To evaluate the utilisation of CT diagnostic imaging in patients admitted to
      hospital with a clinical diagnosis of stroke, and to identify factors which
      influence the use of CT imaging in stroke. Two hundred and fifty consecutive (155
      females) stroke patients were assessed median age 76 years (range 39-95 y).
      Ninety-seven patients underwent CT scanning; median time to scan from admission
      was two days (range 0-43). The time to CT scanning was significantly shorter in
      patients aged < 65 years (p < 0.001), and in patients with a non-disabling stroke
      (p < 0.05). The factors (odds ratios and 95% confidence limits) significantly
      associated with CT scanning were male sex (2.21:1.31-3.74); normal Glasgow coma
      score (2.48:1.59-3.85); Rankin score 1-3 (6.40:1.74-23.56); age < 65 years
      (10.23:4.49-23.32) and no previous cerebrovascular event (1.97:1.10-3.51). In
      this study, those patients who would benefit most from medical intervention with
      antiplatelet agents to reduce the risk of recurrence were more likely to receive
      CT diagnostic imaging.

PMID- 8290938
TI  - Social deprivation indices of patients on renal replacement therapy (RRT) in
      Grampian.
AB  - The social deprivation scores of 169 patients who resided in Grampian region and
      commenced renal replacement therapy (RRT) in Aberdeen during the period 1 January
      1985-30 June 1991 were measured when their serum creatinine concentrations were
      first > = 300 mumol/l, using the Jarman Underprivileged Area (UPA) and Carstairs
      indices. The numbers in the population of Grampian for each score were obtained
      from the Information Services team of Grampian Health Board based on the 1981
      census. Comparison of the numbers of patients in each category of both Jarman and
      Carstairs indices showed no differences between the observed numbers of patients
      and the numbers in the general population. Thus in this study social deprivation
      occurred no more frequently in those commencing RRT than in the general
      population.

PMID- 8290939
TI  - Outcome of treating thyrotoxic patients with a standard dose of radioactive
      iodine.
AB  - This is a report of an audit exercise that was designed to study the
      effectiveness of treating thyrotoxic patients with a standard dose--370 MBq--of
      radioactive iodine (131l). This treatment was received by 183 patients in one
      centre between 1977 and 1989. The results were assessed from the answers to 114
      questionnaires that had been completed by the patients' general practitioners.
      The patients were aged between 28 and 85 years; 86% were female; 42% had been
      treated previously with anti-thyroid drugs. Ninety-five of the patients (83%)
      became euthyroid after a single dose of 131l; 18 required one further dose; and
      one required two further doses. At the time of the survey, 32 (28%) were
      euthyroid, while 82 patients (72%) had become hypothyroid and required treatment
      with thyroxine. Within five years of treatment, 85% of the patients had become
      hypothyroid. These results are compared with those from two other centres.

PMID- 8290940
TI  - A local review of domiciliary consultations.
AB  - This report examines the trends and patterns of domiciliary consultations within
      Lothian Health Board area. Lothian Health Board is the second largest health
      board in Scotland. It is a teaching board with a mixed urban and rural population
      of 750,000. This is a retrospective study of data on domiciliary consultations
      from the Information and Statistic Division of the Common Services agency for the
      years 1986 to 1991. Comparison of total figures nationally and locally and an
      examination of numbers of visits among specialties within the health board area.
      Between 1986 and 1991 the total number of domiciliary consultations in Scotland
      dropped by 27%. During the same period the average rate for three of the four
      Scottish teaching boards fell by 32% while for Lothian it fell by 20%. Average
      teaching board figures dropped consistently each year but Lothian figures showed
      more fluctuation, in particular, a drop of 20% between 1990 and 1991. The large
      drop in domiciliary visits was reflected in two of the three main specialties for
      the same period.

PMID- 8290941
TI  - Central nervous system histiocytosis X--imaging and responses to chemotherapy.
AB  - Histiocytosis X is the term first coined by Lichtenstein in 1953 to describe a
      heterogeneous group of disorders which is considered now to include Hand-Schuller
      Christian disease, Letterer-Siwe disease and Eosinophilic Granuloma of bone.
      Gagel, in 1941, first described involvement of the central nervous system (CNS)
      in Histiocytosis X--in this case the hypothalamus and posterior pituitary were
      the areas principally affected. CNS involvement outwith these areas is rare,
      generally difficult to diagnose, and little information on treatment is
      available. In this case we describe a man with cranial histiocytosis X who was
      treated with intrathecal and systemic chemotherapy and cranial irradiation, and
      we comment upon the value of magnetic resonance imaging (MRI) in this condition.

PMID- 8290942
TI  - Potential developments in rehabilitation care.

PMID- 8290943
TI  - Comment on medical practice in Scotland in the time of William Cullen and on
      Cullen's medical doctrine.

PMID- 8290944
TI  - Minnesota drug sales.

PMID- 8290945
TI  - Minnesota drug sales.

PMID- 8290946
TI  - ApoE, amyloid, and Alzheimer's disease.

PMID- 8290947
TI  - Feds drop Gallo criminal probe.

PMID- 8290948
TI  - French AIDS scandal. Letters provoke unintended response.

PMID- 8290949
TI  - MicroGeneSys. Peer review triumphs over lobbying.

PMID- 8290950
TI  - Researchers nervous about bioethics bill.

PMID- 8290951
TI  - Another shakeup at LBL genome center.

PMID- 8290952
TI  - New radon study: no smoking gun.

PMID- 8290953
TI  - Learning by diffusion: nitric oxide may spread memories.

PMID- 8290954
TI  - Radiation: balancing the record.

PMID- 8290955
TI  - Political fallout: a national bioethics board?

PMID- 8290956
TI  - Ecological and genetic factors in conservation: a cautionary tale.

PMID- 8290957
TI  - Alpha-helical coiled coils: more facts and better predictions.

PMID- 8290958
TI  - Molecular dynamics in liquids: spin-lattice relaxation of nitroxide spin labels.
AB  - Time domain pulsed saturation recovery and electron-electron double resonance
      spectroscopies were used to measure the spin-lattice relaxation rates of the
      electron and the nitrogen nucleus in nitroxide spin labels in liquids. The
      rotational correlation time range covered is from picoseconds to milliseconds.
      These rates are quantitatively explained by isotropic rotational Brownian
      dynamics, which modulate the interactions between the electron spin and the
      molecular angular momentum; the nitrogen and electron spins; and the solvent
      protons with both the electron and the nitrogen spins. This solves a 20-year-old
      problem that has limited scientific applications of nitroxides.

PMID- 8290959
TI  - Meiosis-induced double-strand break sites determined by yeast chromatin
      structure.
AB  - Double-strand DNA breaks (DSBs) occur at recombination hotspots during
      Saccharomyces cerevisiae meiosis and are thought to initiate exchange at these
      loci. Analysis of DSB sites in three regions of the yeast genome indicated that
      breaks occur at or near many potential transcription promoters and that DSBs
      initiate most, if not all, meiotic recombination. DSB sites displayed
      deoxyribonuclease I hypersensitivity in chromatin from mitotic and meiotic cells,
      and changes in chromatin structure produced parallel changes in the occurrence of
      DSBs. Thus, features of chromatin structure that are established before meiosis
      play a role in determining where meiotic recombination events initiate.

PMID- 8290960
TI  - Parallel neuronal mechanisms for short-term memory.
AB  - Although objects that have just been seen may persist in memory automatically for
      a time and interact passively with incoming stimulation, some tasks require that
      the memory be actively maintained and used. To test for the existence of separate
      automatic and volitional mechanisms of short-term memory, recordings were made
      from neurons in the inferior temporal cortex of monkeys while the monkeys held a
      sample picture "in mind" and signaled when it was repeated in a sequence of
      pictures, ignoring other stimulus repetitions. Some neurons were suppressed by
      any picture repetition, regardless of relevance, whereas others were enhanced,
      but only when a picture matched the sample. Short-term memory appears to reflect
      the parallel operation of these two mechanisms--one being automatic and the other
      active.

PMID- 8290961
TI  - Phospholipase D: a downstream effector of ARF in granulocytes.
AB  - Activation of the phospholipase D (PLD) pathway is a widespread response when
      cells are activated by agonists that bind receptors on the cell surface. A 16-kD
      cytosolic component can reconstitute guanosine triphosphate (GTP)-mediated
      activation of phospholipase D in HL60 cells depleted of their cytosol by
      permeabilization. This factor was purified and identified as two small GTP
      binding proteins, ARF1 and ARF3. Recombinant ARF1 substituted for purified ARF
      proteins in the reconstitution assay. These results indicate that phospholipase D
      is a downstream effector of ARF1 and ARF3. The well-established role of ARF in
      vesicular traffic would suggest that alterations in lipid content by PLD are an
      important determinant in vesicular dynamics.

PMID- 8290962
TI  - Maspin, a serpin with tumor-suppressing activity in human mammary epithelial
      cells.
AB  - A gene encoding a protein related to the serpin family of protease inhibitors was
      identified as a candidate tumor suppressor gene that may play a role in human
      breast cancer. The gene product, called maspin, is expressed in normal mammary
      epithelial cells but not in most mammary carcinoma cell lines. Transfection of
      MDA-MB-435 mammary carcinoma cells with the maspin gene did not alter the cells'
      growth properties in vitro, but reduced the cells' ability to induce tumors and
      metastasize in nude mice and to invade through a basement membrane matrix in
      vitro. Analysis of human breast cancer specimens revealed that loss of maspin
      expression occurred most frequently in advanced cancers. These results support
      the hypothesis that maspin functions as a tumor suppressor.

PMID- 8290963
TI  - Locally distributed synaptic potentiation in the hippocampus.
AB  - The long-lasting increase in synaptic strength known as long-term potentiation
      has been advanced as a potential physiological mechanism for many forms of both
      developmental and adult neuronal plasticity. In many models of plasticity,
      intercellular communication has been proposed to account for observations in
      which simultaneously active neurons are strengthened together. The data presented
      here indicate that long-term potentiation can be communicated between synapses on
      neighboring neurons by means of a diffusible messenger. This distributed
      potentiation provides a mechanism for the cooperative strengthening of proximal
      synapses and may underlie a variety of plastic processes in the nervous system.

PMID- 8290964
TI  - Experimental support for the "hydrophobic zipper" hypothesis.

PMID- 8290965
TI  - Alzheimer's disease and possible gene interaction.

PMID- 8290966
TI  - Idarubicin plus continuous-infusion high-dose cytarabine as treatment for
      patients with acute myelogenous leukemia or myelodysplastic syndrome.
AB  - Combination therapy with idarubicin plus continuous-infusion, high-dose
      cytarabine in patients with newly diagnosed acute myelogenous leukemia resulted
      in an improved complete response rate over historic controls who received either
      (1) Adriamycin or amsacrine in combination with standard-dose cytarabine or (2)
      continuous-infusion, high-dose cytarabine alone or in combination with amsacrine
      or mitoxantrone. The complete response rate in patients with acute myelogenous
      leukemia was similar to that in patients with refractory anemia with excess
      blasts in transformation.

PMID- 8290967
TI  - Idarubicin for remission induction of acute myeloid leukemia: United Kingdom
      multicenter experience.
AB  - Ninety-eight adult patients with acute myeloid leukemia were given variable
      remission induction/consolidation regimens containing idarubicin. Sixty-nine
      (70%) were new cases (median age, 56 years) and 29 (30%) were in relapse (n = 24)
      or had primary refractory disease (n = 5) (median age, 46 years). Complete
      remission (CR) rates were 57% (39 of 69 patients) of the newly diagnosed
      patients, with no difference for those below or above 55 years of age (56% v 59%)
      or for patients exhibiting white blood cell counts of less or more than 50 x
      10(9)/L (52% v 69%; P = .8). Of the 39 patients who achieved CR, 26 (67%, 38% of
      the total number of patients) remain in CR with a median follow-up of 3 months
      (range, 0 to 61 months). Forty-two percent of the relapsed cases (10 of 24
      patients) and 60% of the primary refractory disease cases (three of five
      patients) achieved CR. Of these 13 responders, six are alive (three continuing in
      CR and three relapsed) with a median follow-up of 3 months (range, 1 to 20
      months), and seven have died with a median survival of 7 months (range, 0 to 12
      months). Of the 52 patients who have achieved CR, 84% did so with one course of
      treatment and 16% with two courses. The presence of normal cytogenetic analysis
      or favorable chromosomal aberrations significantly improved overall CR rates. The
      patients in this study had significantly more unfavorable cytogenetic
      abnormalities than the historic controls. Reported toxicity was hepatic in 13%,
      cardiac in 9%, and renal in 7% of all cases. These data suggest a comparable
      efficacy of idarubicin to other anthracyclines in remission induction of acute
      myeloid leukemia, with a promising role in relapsed/refractory disease.

PMID- 8290968
TI  - Idarubicin/cytosine arabinoside and mitoxantrone/etoposide for the treatment of
      de novo acute myelogenous leukemia.
AB  - Since January 1989, 56 patients (31 females and 25 males) with de novo acute
      myelogenous leukemia have been included in the study. Their median age was 43
      years (range, 15 to 60 years) with a distribution according to French-American
      British morphologic subtypes as follows: six M1, 14 M2, four M3, 19 M4, nine M5,
      two M6, and two M7. The induction regimen (IDAC) consisted of idarubicin (12
      mg/m2/d intravenously [IV] days 1 to 3) in combination with cytarabine (100
      mg/m2/d continuous IV days 1 to 7). Patients achieving complete remission (CR) or
      partial remission received another cycle of IDAC followed by NOVE (mitoxantrone
      10 mg/m2/d IV days 1 to 5 and etoposide 100 mg/m2/d IV days 1 to 5). Fifty-four
      patients are evaluable for response: after two cycles of IDAC, 42 patients had
      attained CR (78%), while 76% of these had already reached CR after the first
      cycle. Of the initial 11 nonresponders to IDAC, four obtained CR after NOVE.
      Thus, 46 of 54 patients (85%) achieved CR after sequential treatment with IDAC
      and NOVE. In the last 17 patients who entered CR or partial remission after the
      first cycle of IDAC, recombinant human granulocyte-macrophage colony-stimulating
      factor (rhGM-CSF; 3 micrograms/kg/d) was administered for 6 days starting 3 days
      prior to the second cycle of IDAC. For consolidation with NOVE, rhGM-CSF was
      given according to the same dosage schedule. After 72 hours of rhGM-CSF
      treatment, the white blood cell count showed a median 3.9-fold increase, without
      appearance of myeloblasts in the peripheral blood. During sequential
      chemotherapy, no significant complications (in particular, no major cardiac
      toxicity) were observed. Postremission, patients were either given bone marrow
      transplants, received late consolidation with high-dose cytarabine/mitoxantrone,
      or were followed up without any further treatment. Of the 46 patients evaluable
      for disease-free survival, 21 patients (45%) remain in CR with a 34% probability
      of disease-free survival at 37 months. The response-adapted treatment with
      IDAC/NOVE is effective and very well tolerated. To define the therapeutic impact
      of rhGM-CSF, a randomized trial will be required.

PMID- 8290969
TI  - Idarubicin in the therapy of acute myeloid leukemia: final analysis in 57
      previously untreated patients.
AB  - Fifty-seven previously untreated adult acute myeloid leukemia patients received
      idarubicin (IDA) in sequential combination with cytarabine as induction therapy;
      post-remission treatment included two courses of IDA and cytarabine alternating
      with two courses of VP-16 and cytarabine. As late intensification, patients
      received either high-dose cytarabine or, in 10 cases, autologous bone marrow
      transplantation. Complete remission (CR) was achieved in 48 patients (84.2%), 41
      after one induction course and seven after two courses. Median length of disease
      free survival (DFS) was 26 months. Univariate analysis did not identify any of
      the investigated variables as having prognostic significance in predicting DFS.
      On the other hand, patients achieving CR after one induction course had a better
      DFS than those requiring two courses. Furthermore, the analysis of DFS slightly
      favors autologous bone marrow transplantation. In conclusion, the antileukemic
      activity of the present IDA protocol is testified by the high CR rate and by the
      possibility of minimizing the role of prognostic factors. The better outcome of
      patients achieving CR after one induction course further supports the opinion
      that the intensity of the induction treatment, offered by an agent as potent as
      IDA, might significantly influence DFS.

PMID- 8290970
TI  - Results of treatment with an intensive combination induction regimen containing
      idarubicin in children with acute myeloblastic leukemia: preliminary report of
      the Argentine Group for Treatment of Acute Leukemia.
AB  - In April 1990, the Argentine Group for Treatment of Acute Leukemia began a
      multicenter trial for the treatment of previously untreated acute myeloblastic
      leukemia patients who were under 21 years of age. Initial treatment consisted of
      an 8-day induction phase with cytarabine together with idarubicin on days 3 to 5
      and etoposide on days 6 to 8. A multidrug consolidation phase was subsequently
      administered and, after a treatment-free interval of 2 to 4 weeks, two 5-day
      intensification courses with high-dose cytarabine and etoposide were delivered
      with a 4-week interval between each course. Continuation therapy was started 2 to
      4 weeks after the second course, with 6-thioguanine daily and cytarabine daily
      for 4 days every 4 weeks. Treatment was stopped after 18 months in children in
      continuous complete remission. A preliminary evaluation of this ongoing study
      included 36 patients with a mean age of 7.5 years (age range, 5 months to 16
      years). The majority of patients had a French-American-British classification of
      M2 (n = 13) or M4 (n = 8). Complete remission was achieved by 91.7% of patients,
      while one died from sepsis in bone marrow hypoplasia and two were regarded as
      treatment failures. At a median follow-up of 12 months (range, 2 to 23 months)
      there were 12 adverse events: six bone marrow relapses, one bone marrow/skin
      relapse, and five deaths in complete remission (all deaths occurred during the
      consolidation phase). During the induction phase most of the patients experienced
      prolonged myelosuppression, and grade 3 to 4 toxicity (according to the
      Children's Cancer Group criteria) was frequently seen. Alopecia was universal.
      However, toxicity was manageable. We conclude that idarubicin in combination with
      cytarabine and etoposide is a highly effective regimen for induction in children
      with acute myeloblastic leukemia.

PMID- 8290971
TI  - Idarubicin-related side effects in recipients of T-cell-depleted allogeneic bone
      marrow transplants are schedule dependent.
AB  - The influence of three different dosage schedules of anthracycline (idarubicin or
      daunorubicin)-intensified preparative therapy prior to T-cell-depleted allogeneic
      bone marrow transplantation (BMT) on (1) the severity and duration of oral
      toxicity (mucositis), (2) the duration of bone marrow aplasia, and (3) overall
      survival, relapse, and disease-free survival was studied in 99 BMT patients with
      standard- or high-risk hematologic malignancies. A further 146 patients who did
      not receive the anthracycline-intensified conditioning served as (historic)
      controls. All patients received cyclophosphamide (total dose, 120 mg/kg) on days 
      6 and -5 and total body irradiation on days -2 and -1 prior to BMT. The 99
      patients who received the anthracycline-intensified preparative regimen were
      given either idarubicin (total dose, 42 mg/m2; n = 88) or daunorubicin (total
      dose, 156 mg/m2; n = 11) by continuous intravenous infusion between days -7 and 
      1 prior to BMT in 59 cases (cohort 1), on days -8 and -7 in 17 cases (cohort 2),
      and on days -12 and -11 in 23 cases (cohort 3). The occurrence of severe oral
      mucositis and delayed bone marrow recovery was schedule dependent, being
      substantially lower with earlier administration of the anthracycline-intensified
      regimen on days -12 and -11 before BMT (cohort 3), in comparison with later
      administration (cohorts 1 and 2). Plasma drug and metabolite concentrations were
      measured in 11 patients who received idarubicin. At the time of allogeneic bone
      marrow infusion (day 0), patients in cohorts 1 and 2 had plasma concentrations of
      idarubicin and idarubicinol (its active metabolite) in the range of in vitro
      cytotoxicity. However, in cohort 3, plasma concentrations on day 0 were much
      lower, which correlated with the lower maximum intensity and shorter duration of
      mucositis in these patients. In terms of overall survival, relapse rate, and
      disease-free survival in standard-risk patients, the anthracycline-intensified
      regimen proved to be very effective. Transplant-related mortality was 25% in the
      anthracycline group compared with 32% in the controls. The probability of relapse
      also was significantly less in the anthracycline group in comparison with
      controls (17% v 46%; P < .001), and the probabilities of long-term overall and
      disease-free survival were significantly greater (71% v 37% [P < .01] and 63% v
      32% [P < .01], respectively). Only three patients in the idarubicin group
      experienced cardiotoxicity (one in each cohort); the causative relationship with
      anthracyclines was considered likely in one, possible in one, and doubtful in the
      third.

PMID- 8290972
TI  - The neurologically compromised fetus.

PMID- 8290973
TI  - Chromosomal abnormalities in the newborn period.
AB  - Chromosomal abnormalities account for a significant percentage of congenital
      malformations in the neonate. While some of the syndromes can be suspected on
      clinical grounds, the clinician will need to have a high index of suspicion based
      on the presence of multiple abnormalities that cannot be accounted for by other
      causes. Chromosome analysis should be performed promptly in these cases. Cultured
      lymphocytes are the standard preparation at present. However, new non-isotopic
      hybridization techniques are becoming available that allow analysis of interphase
      cells, and these may become more widely used as clinical experience with them is
      gained. Prognosis can usually be better defined once the chromosome analysis is
      complete. The information acquired may also be used to provide risk estimates for
      chromosomal abnormalities in future pregnancies of the parents of the affected
      infant and for other relatives. Empathetic counseling of the parents and family
      must be provided once the diagnosis is known. It must take into account the
      knowledge the chromosome analysis provides, be respectful of the parent's need
      for support, and be accurate as to prognosis of the condition diagnosed. When
      Down syndrome and Turner syndrome have been diagnosed, care must be taken to
      emphasize the positive aspects of the prognosis. When a chromosomal abnormality
      with an extremely poor prognosis is identified, support for withdrawal of medical
      intervention must be sensitively provided. The diagnosis and care of an infant
      with a chromosomal abnormality will challenge all of the pediatrician's
      diagnostic, therapeutic, and communication skills.

PMID- 8290974
TI  - Metabolic disease of the neonate and young infant.
AB  - The inborn errors of metabolism must always be considered when a newborn presents
      with neurological distress, feeding difficulties, or a family history of neonatal
      or unexplained death. Clinical suspicion combined with prompt sophisticated
      laboratory evaluation is crucial if infants affected with this group of disorders
      are to be rescued.

PMID- 8290975
TI  - Mechanisms of perinatal hypoxic-ischemic brain damage.

PMID- 8290976
TI  - Risk period for intraventricular hemorrhage of the preterm neonate is independent
      of gestational age.

PMID- 8290977
TI  - Preterm periventricular axonal and myelin injury.
AB  - Injury to the periventricular axons and myelin in the preterm infant occur at a
      vulnerable period of brain development and may be associated with devastating
      brain lesions and neurological sequelae. Ultrasonography in the newborn period
      identifies the site and extent of lesions and is useful in predicting the outcome
      for surviving infants. The etiology of the most common lesion, PVL, is
      incompletely understood and will require continuing studies so that causes may be
      eliminated and appropriate therapies instigated.

PMID- 8290978
TI  - Neonatal seizures.

PMID- 8290979
TI  - Neurological, cognitive, and behavioral sequelae of hypoxic-ischemic
      encephalopathy.

PMID- 8290980
TI  - [The status of the national health service. A critical commentary].

PMID- 8290981
TI  - [The role of the nursing director for the quality of the nursing service].

PMID- 8290982
TI  - [The fundamentals for performance evaluation].

PMID- 8290983
TI  - [An analysis of the conceptual nursing model of Jean Watson].

PMID- 8290984
TI  - [Mental disorders related to hashish consumption. Interview by M. Vigy].

PMID- 8290985
TI  - [Nursing, an autonomous profession. The challenge of the future].

PMID- 8290986
TI  - [Burns in children. The general aspects].

PMID- 8290987
TI  - [MAQCEH. A method for evaluating the quality of hospital nursing care. The adult
      confined to bed].

PMID- 8290988
TI  - [Towards a nursing ethics].

PMID- 8290990
TI  - [Dilemmas in the exercise of nursing in a practical approach to ethical
      decisions].

PMID- 8290989
TI  - [Drugs: they are the great problem of the human genus].

PMID- 8290991
TI  - [Watching over the elderly. The profile of osteoporosis].

PMID- 8290992
TI  - [The cycle of life. Death, the terminal patient--nursing care].

PMID- 8290993
TI  - [The inauguration of a new building for the Leiria College of Nursing].

PMID- 8290994
TI  - Using our influence and persuasion to get quality products.

PMID- 8290995
TI  - Spina bifida. Part 3. Implications for bladder and bowel management.

PMID- 8290996
TI  - Secondary complications after spinal cord injury.

PMID- 8290997
TI  - Electrostimulation of the bladder neck in acontractile bladder: two case reports.

PMID- 8290998
TI  - Stress urinary incontinence in women: surgical treatment.

PMID- 8290999
TI  - Urinary incontinence in community dwelling elders.

PMID- 8291000
TI  - Urodynamic evaluation of patients with vesicostomy.

PMID- 8291001
TI  - Male external collecting devices: management of a difficult case.

PMID- 8291002
TI  - Safer, more efficient specimen collection.

PMID- 8291003
TI  - Lethal catheter syndrome.

PMID- 8291005
TI  - Notice of duplication. Fundamentals of urodynamics. Part 1. Normal bladder
      function and patient assessment.

PMID- 8291004
TI  - The "Beth" bag.

PMID- 8291006
TI  - Imaging shoulder impingement.
AB  - Appropriate imaging and clinical examinations may lead to early diagnosis and
      treatment of the shoulder impingement syndrome, thus preventing progression to a
      complete tear of the rotator cuff. In this article, we discuss the anatomic and
      pathophysiologic bases of the syndrome, and the rationale for certain imaging
      tests to evaluate it. Special radiographic projections to show the supraspinatus
      outlet and inferior surface of the anterior third of the acromion, combined with
      magnetic resonance images, usually provide the most useful information regarding
      the causes of impingement.

PMID- 8291007
TI  - Aggressive fibrous dysplasia of the maxillary sinus.
AB  - Fibrous dysplasia is usually a slowly progressive, benign disease that develops
      over several years and presents with deformity or mild symptomatology. Five of 34
      patients (ages 4-21 years), who were subsequently diagnosed histologically as
      having fibrous dysplasia of the maxillary sinus, rapidly developed soft tissue
      masses of the malar region over a period of less than 4 months with accompanying
      pain (2 patients) and nasal obstruction and exophthalmos (2 patients). Each was
      clinically suspected of having a sarcoma; two had been thought to have an
      "osteofibrosarcoma" on initial biopsy at outside hospitals. After resection, all
      lesions developed regrowth. At histopathologic examination, both initial and
      recurrent masses proved to be typical fibrous dysplasia with spicules of woven
      bone in cellular, sometimes vascular, fibrous tissue. No malignant degeneration
      was found. On conventional radiography, aggressive fibrous dysplasia produced
      opacification and expansion of the maxillary sinus and apparent disruption of its
      wall with an associated soft tissue mass. Computed tomography (CT) demonstrated
      voluminous heterogeneous masses with "ground glass appearance", calcifications,
      areas of enhancement, low attenuation, cystic areas, and a thinned, sometimes
      interrupted, maxillary wall. Despite the aggressive clinical course for both
      initial and recurrent lesions, the CT findings of a "ground glass" mass with
      calcifications surrounded by a maxillary sinus wall, even if incomplete, can
      suggest the diagnosis of aggressive fibrous dysplasia.

PMID- 8291008
TI  - Mesenchymal hamartoma of the chest wall in infants and children: a
      clinicopathological study of five patients.
AB  - Mesenchymal hamartoma of chest-wall is a rare benign lesion that has varied
      histological characteristics and usually occurs during early infancy. We report
      the histological characteristics of mesenchymal hamartoma found in five patients
      aged respectively 25 days, 5 months, 8 months, and 4 and 8 years at presentation.
      Two patients presented with respiratory distress, two with an asymptomatic chest
      wall mass, and one with a deformity of the left chest wall. Surgical resection
      was performed on four patients and a biopsy only in one patient. Overall, the
      tumors were well delineated, lobulated, tan to reddish in color, and on section
      showed blood-filled cystic spaces with interspersed small islands of cartilage
      and fibrous tissue. Histological analyses demonstrated mixtures of bone
      trabeculae with spindle-cell stroma, chondroblast-like proliferation, mature and
      immature hyaline cartilage, and aneurysmal bone cyst formation. All patients are
      alive and well without evidence of disease. Despite the alarming clinical and
      histologic presentation, mesenchymal hamartoma of the chest wall is a non
      neoplastic benign lesion.

PMID- 8291009
TI  - Magnetic resonance imaging of bone destruction in rheumatoid arthritis:
      comparison with radiography.
AB  - Bony changes in forty-four knees of patients with clinically established
      rheumatoid arthritis (RA) were examined using magnetic resonance imaging (MRI)
      and plain film radiography. In all cases MRI was clearly superior to radiographs,
      demonstrating 25 marginal erosions and 42 subchondral cysts, while the number
      seen on radiographs was 3 and 8, respectively. These results emphasize the
      problems in visualizing bone erosions in large joints using plain films. MRI is
      the method of choice for detecting early changes in RA, not only because of its
      high sensitivity, but also because of the ability of contrast-enhanced MRI to
      provide physiological characterization of these lesions.

PMID- 8291010
TI  - Anatomical and radiological observations concerning ossification of the
      sacrotuberous ligament: is there a relation to spinal diffuse idiopathic skeletal
      hyperostosis (DISH)?
AB  - In a collection of 101 anatomical preparations of the human pelvis, ossification
      of the sacrotuberous ligament was found in 8 cases. In 7 of these, the
      ossification showed a characteristic intraligamentous morphology, with a broad
      based origin at the ischial tuberosity and tapering off craniomedially. The
      length varied between 1.1 and 7.2 cm. The surface of the bone formations appeared
      fasciculated, except in one case which had a wax-like flowing bone formation
      lying upon the sacrotuberous ligament. Careful anatomical and radiological
      examination of the spine, the ulnae, the calcanei and the iliac crests in these 8
      cases, revealed in only one case any findings (spurs at the olecranon) that could
      be attributed to extraspinal manifestations of diffuse idiopathic skeletal
      hyperostosis (DISH). Indeed, in no case were the most widely accepted diagnostic
      criteria of DISH, the spinal alterations, seen. We therefore suggest that
      ossification of the sacrotuberous ligament is an autonomous finding and not a
      good indicator of the presence of spinal DISH.

PMID- 8291011
TI  - Benign osteopetrosis: a review of 42 cases showing two different patterns.
AB  - Radiographs of 42 patients with benign osteopetrosis were reviewed. Clinical
      notes were available for approximately half of these. According to the
      classification of Bollerslev and Andersen in 1987, 29 patients had type II
      disease of whom 18 sustained fractures. Thirteen patients had type I disease;
      only one of these patients sustained fractures. Transverse banding of the
      metaphyses was a common feature in type II disease; it was not seen in any of the
      type I cases. This review confirms that type II patients are at high risk of
      fracture, while type I patients are not. The presence of sclerotic metaphyseal
      bands distinguishes between the two types, its presence being enough to confirm
      type II. However, its absence is not an indication of type I disease, since it is
      not seen in all cases of type II. Banding does not correlate with liability to
      fracture. Typing patients with the benign form of osteopetrosis is important in
      order to anticipate the fracture pattern.

PMID- 8291012
TI  - Extensive skeletal metastases from chondrosarcoma without pulmonary involvement.
AB  - Among 251 patients who presented to our orthopedic oncology unit over the last 20
      years with chondrosarcoma, we identified two patients with low to intermediate
      grade conventional chondrosarcoma who developed multifocal bone metastases in the
      absence of pulmonary spread. The metastatic lesions were of a similar histologic
      grade to the primary site. One of the patients had synchronous foci, while the
      other developed the bone lesions 3 years after initial presentation. The unusual
      behavior of these cases, as well as the possibility that they may represent
      instances of multicentric chondrosarcoma, is discussed.

PMID- 8291013
TI  - Arthrographic pseudotear of the anterior horn of the lateral meniscus caused by a
      displaced meniscal fragment.

PMID- 8291014
TI  - Case report 797: "Dedifferentiated" lipoma-like liposarcoma of soft tissue with
      focal transformation to high-grade "sclerosing" osteosarcoma.
AB  - We have presented the first case of a lipoma-like liposarcoma of the soft tissues
      with high-grade malignant transformation to a high-grade osteosarcoma, the latter
      component of which responded well to systemic chemotherapy. With 4 months of
      follow-up the patient is without evidence of disseminated disease. The various
      types of liposarcoma are listed and several described in some detail. Of
      particular importance is the potential for development of a highly malignant
      sarcoma from a relatively indolent low-grade liposarcoma, with even osteosarcoma
      developing.

PMID- 8291015
TI  - Case report 814: Fibrolipoma of the median nerve.
AB  - A case of fibrolipoma of the median nerve was described. Peripheral nerve tumors
      of the upper extremity are very rare. Within this group of tumors, the
      fibrolipoma is an exceedingly uncommon entity. It was first described in 1953,
      and to date less than 100 cases have been described. The purpose of this report
      was to point out a characteristic sign of fibrolipoma, which in our opinion
      allows distinction on CT and MRI between fibrolipoma and the other peripheral
      nerve and fatty soft tissue tumors.

PMID- 8291016
TI  - Case report 815: Tear of the rotator interval.
AB  - Rotator interval tears are an uncommon, but clinically important subtype of
      rotator cuff tear. As MRI assumes an ever increasing role in the imaging
      evaluation of the painful shoulder, radiologists must be aware of this entity and
      appreciate the difficulty in diagnosing these tears with MRI. Differentiation of
      a true rotator interval tear from normal synovium and capsule in this space is
      most likely not possible with MRI, and symptoms may be referred and misleading.
      It is therefore important to correlate the MR findings with the clinical history
      and physical examination.

PMID- 8291017
TI  - Case report 816: Rapid acceleration of osteolysis from loose cemented total hip
      replacement.

PMID- 8291018
TI  - Case report 817: Synovial chondrosarcoma secondary to synovial chondromatosis.
AB  - A case of prolonged history of synovial chondromatosis of the knee joint that
      transformed into low-grade chondrosarcoma was reported. The pathological
      differentiation of this rare entity from synovial chondromatosis has been
      discussed, as have the radiographic appearance and differential diagnosis.

PMID- 8291019
TI  - Subchromosomal localization of a gene (XRCC5) involved in double strand break
      repair to the region 2q34-36.
AB  - We have previously shown that human chromosome 2 can complement both the
      radiation sensitivity and the defect in double strand break rejoining
      characteristic of ionizing radiation (IR) group 5 mutants. A number of human
      hamster hybrids containing segments of human chromosome 2 were obtained by
      microcell transfer into two group 5 mutants. In most, but not all, of these
      hybrids, the repair defect was complemented by the human chromosomal DNA. Two
      complementing microcell hybrids were irradiated and fused to XR-V15B, an IR group
      5 mutant, to generate further hybrids bearing smaller regions of chromosome 2.
      All hybrids were examined for complementation of the repair defect. The region of
      chromosome 2 present was determined using PCR with primers specific for various
      human genes located on chromosome 2. A complementing hybrid bearing only a small
      region of chromosome 2 was finally generated. From this analysis we deduced that
      the XRCC5 gene was tightly linked to the marker, TNP1, which is located in the
      region 2q35.

PMID- 8291020
TI  - Caffeine enhanced measurement of mutagenesis by low levels of gamma-irradiation
      in human lymphocytes.
AB  - The well-known action of caffeine in synergizing mutagenesis (including
      chromosome aberrations) of agents like ionizing radiation by inhibition of
      cellular repair processes has been incorporated into a rapid procedure for
      detection of mutagenicity with high sensitivity. Effects of 5-10 rads of gamma
      irradiation, which approximate the human lifetime dose accumulation from
      background radiation, can be detected in a two-day procedure using an
      immortalized human WBC culture. Chromosomally visible lesions are scored on cells
      incubated for 2 h after irradiation in the presence and absence of 1.0 mg/ml of
      caffeine. An eightfold amplification of scorable lesions is achieved over the
      action of radiation alone. This approach provides a closer approximation to
      absolute mutagenicity unmitigated by repair processes, which can vary in
      different situations. It is proposed that mutagenesis testing of this kind, using
      caffeine or other repair-inhibitory agents, be employed to identify mutagens in
      their effective concentrations to which human populations may be exposed; to
      detect agents such as caffeine that may synergize mutagenic actions and pose
      epidemiologic threats; and to discover effective anti-mutagens. Information
      derived from the use of such procedures may help prevent cancer and newly
      acquired genetic disease.

PMID- 8291021
TI  - Genetic diversity of mitomycin C-hypersensitive Chinese hamster cell mutants: a
      new complementation group with chromosomal instability.
AB  - A Chinese hamster cell mutant (V-C8) isolated previously, which is approximately
      100 fold more sensitive to mitomycin C (MMC) than its parental wild-type V79
      cells (judged by D10 values), was further characterized. V-C8 cells exhibit an
      increased sensitivity towards other cross-linking agents, such as cis-DDP
      (approximately 40-fold), DEB (approximately 30-fold), and also to adriamycin
      (approximately 5-fold), and the monofunctional alkylating agents: MMS
      (approximately 5-fold) and EMS (approximately 6-fold). V-C8 cells show a higher
      level induction of chromosomal aberrations by cross-linking agents (MMC, cis-DDP,
      and DEB) and an increased level of spontaneous chromosomal aberrations in
      comparison to the wild-type V79 cells. To determine whether the V-C8 mutant
      represents a new complementation group among Chinese hamster cell mutants that
      also display the extreme sensitivity to MMC, V-C8 cells were fused with irs1,
      irs1SF, UV20, UV41, and V-H4 cells. In all cases, the derived hybrids regained
      the MMC sensitivity similar to wild-type cells, indicating that the V-C8 mutant
      belongs to a new sixth complementation group.

PMID- 8291022
TI  - Adenovirus-mediated correction of the genetic defect in hepatocytes from patients
      with familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an inherited deficiency of LDL receptors
      that has been an important model for liver-directed gene therapy. We are
      developing approaches for treating FH that are based on direct delivery of
      recombinant LDL receptor genes to liver in vivo. As a first step towards this
      goal, replication-defective recombinant adenoviruses were constructed which
      contained either the lacZ gene or the human LDL receptor cDNA expressed from a
      beta-actin promoter. Primary cultures of hepatocytes were established from two
      patients with homozygous FH and one nonFH patient, and subsequently exposed to
      recombinant adenoviruses at MOIs ranging from 0.1 to 5. Essentially all of the
      cells expressed high levels of the transgene without demonstrable expression of
      an early or late adenoviral gene product; the level of recombinant-derived LDL
      receptor protein in transduced FH hepatocytes exceeded the endogenous levels by
      at least 20-fold. These studies support the utility of recombinant adenoviruses
      for efficient transduction of recombinant LDL receptor genes into human FH
      hepatocytes without expression of viral proteins.

PMID- 8291023
TI  - Complementation analysis of Chediak-Higashi syndrome: the same gene may be
      responsible for the defect in all patients and species.
AB  - Chediak-Higashi Syndrome is an autosomal recessive disorder, characterized by the
      presence of large intracellular granules, particularly lysosomes and melanosomes.
      While the Chediak-Higashi Syndrome is a rare disorder in humans, phenotypically
      similar syndromes are found in other species. Fusion of normal fibroblasts to
      Chediak fibroblasts complements the Chediak disorder, restoring normal lysosome
      size and distribution. Fusion of wild-type with Chediak fibroblasts from human,
      mouse, or mink demonstrates that wild-type fibroblasts can complement any of the
      Chediak fibroblasts. Complementation was not observed in interspecific hybrids
      between Chediak fibroblasts from these species, suggesting that the same gene
      product is defective in humans, mice, and mink.

PMID- 8291024
TI  - The effectiveness of restriction endonucleases in cell killing and mutation.
AB  - The use of restriction endonucleases (RE) to study the importance of DNA break
      end structures in differential cellular response has proved controversial. The
      number of DNA cut sites and the accessibility of RE are recognized examples of
      confounding factors. We have eliminated these factors by comparing the
      effectiveness of isoschizomers. Additionally, we considered for the first time
      the tolerance of the enzymes to cellular conditions. Cell killing and mutation
      were compared to the overall cutting ability of the enzymes in an "intracellular"
      buffer. We found that the activity of each RE combined with its lifetime, under
      simulated cellular conditions, were the overriding factors in determining
      effectiveness.

PMID- 8291025
TI  - Chromosomal localization and cDNA sequence of human BTEB, a GC box binding
      protein.
AB  - Human BTEB cDNA clones have been isolated, sequenced, and the corresponding gene
      has been assigned to human chromosome 9, region q13, by fluorescent in situ
      hybridization and DNA blot analysis using DNAs from hybrid cell clones containing
      a single human chromosome. The cDNA clone encodes a polypeptide of 244 amino
      acids whose sequence shows a high sequence similarity with the rat BTEB (98%
      amino acid identity).

PMID- 8291026
TI  - The gene for the iron sulfur protein of succinate dehydrogenase (SDH-IP) maps to
      human chromosome 1p35-36.1.
AB  - A partial human cDNA clone for the iron-protein (IP) subunit of succinate
      dehydrogenase (EC 1.3.99.1) was used in Southern analyses of restriction enzyme
      digests of genomic human and hamster DNA as well as hamster-human hybrids
      containing a limited number of human chromosomes. The gene for this protein was
      mapped to human chromosome 1. Digestion of genomic DNA with several restriction
      enzymes yielded two fragments detectable on a Southern blot, in contrast to the
      expectations based on the sequence of the cDNA clone. A preliminary analysis of a
      genomic clone with most of the IP gene has indicated the presence of several
      introns containing restriction sites detected by the Southern analysis. This
      genomic clone was also used for subregional mapping by fluorescence in situ
      hybridization (FISH) to human metaphase chromosomes. A single locus in the region
      1p35-36.1 was identified.

PMID- 8291027
TI  - Tunnel restorations. A 3 1/2-year follow up study of Class I and II tunnel
      restorations in permanent and primary teeth.
AB  - During 1988-89, 224 patients with approximal caries in the premolar/molar regions
      were provided with 318 tunnel restorations. In case of perforation of the enamel
      in the enamel/dentin border, (23%), complete Class II-tunnel restorations with
      glass ionomer cement and composite resin were made. In case of "intact" enamel,
      (77%), partial Class I-tunnel restorations were made. The restorations were
      controlled at annual routine recalls and the success rate after 3 1/2 years was
      74% for permanent teeth, and 10% for primary teeth. Restorations in permanent
      teeth, made during the second year of the study were successful in 82%, as
      compared with 62% for restorations made during the first year, indicating a
      learning effect. Failures in the permanent dentition were due to marginal ridge
      fracture (35%), cavitation in the approximal enamel (31%), and recurrent caries
      (38%). Failures in primary teeth were predominantly due to marginal ridge
      fractures (84%). A comparison with the longevity of conventional Class II
      restorations is made and the possible advantages of the present method are
      presented.

PMID- 8291028
TI  - A longitudinal study of dental caries and cariogenic microflora in a group of
      young adults from Goteborg.
AB  - Caries and cariogenic microorganisms were assessed in a group of young adults
      over a 3-year period. A 30% random sample comprising 101 individuals aged 18-19
      years was re-examined under conditions consistent with the baseline survey 3
      years earlier. The means for DFS prevalence and increment were 8.9 and 2,
      respectively. Continuing polarization of the disease was observed, with mean DFS
      score reaching 19.9 in the upper 15% of the frequency distribution. Highest
      caries activity was observed approximally where the increment of manifest and
      incipient lesions averaged 1.3 and 1.6 surfaces, respectively, as compared to
      0.5/0.6 occlusally and 0.2/0.5 bucco-lingually. While the occlusal component
      continued to dominate DF score with 5.7 surfaces, the prevalence of approximal
      lesions increased by 48%, averaging 2.7 surfaces. Frequency distribution showed a
      shift to the right and increasing skewness. The proportion without manifest
      lesions/restorations had declined by 3%. While only 6% of the dentin
      lesions/restorations were found in the lowest quartile, 15% of the individuals
      with highest caries levels accounted for 40% of the total DFS and 58% of the D
      component. Among the 88 subjects who were saliva sampled, salivary mutans
      streptococci were detected in 89.7% and lactobacilli in 83%. Forty-one percent of
      the 18-19-year-olds had high numbers of mutans streptococci (> 5 x 10(5) cfu per
      ml) as compared to 33% at the age of 15-16-years, while high numbers of
      lactobacilli (> 10(5) cfu per ml) were recovered in 21.8% as compared to 14.3%.
      The stability within each range of microorganisms varied depending on the
      baseline level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291029
TI  - A ten-year evaluation of the quality of orthodontic treatment.
AB  - A 10-year evaluation of the quality of orthodontic treatment at the Department of
      Orthodontics, School of Dentistry in Malmo, University of Lund, showed that in
      approximately 3 cases out of 4 (73%) successful results were noted in the
      malocclusions under treatment. In approximately half the cases the ideal
      treatment goal, normal occlusion, was achieved. The treatment was unsuccessful in
      12% and in a large group of patients (15%) the treatment was discontinued due to
      lack of motivation or compliance. More accurate study and documentation of
      subjective need of treatment (motivation, cooperation and social sufficiency)
      would improve the quality of orthodontic care and make it more efficient. Some
      sort of penalty due to distinct lack of patient cooperation might improve
      orthodontic care. Root resorption occurred frequently during orthodontic
      treatment with multiband fixed appliances, but the apical shortening was small
      and without clinical significance.

PMID- 8291030
TI  - The effect of changed smoking habits on marginal alveolar bone loss. A
      longitudinal study.
AB  - Tobacco smoking is a factor claimed to be of influence on alveolar bone loss. The
      purpose of the present study was to investigate whether the effect of changed
      smoking habits is associated with the progress of proximal marginal alveolar bone
      loss as measured on intraoral radiographs. The study comprised 349 individuals
      with twenty or more remaining teeth examined in 1970 and 1980. The bone loss in
      the period was measured as the difference in the ratios "bone height/root length"
      at proximal tooth sides between the two examinations. It was found that the
      marginal bone loss in "Non smokers in 1970 and 1980" was as a mean 3.9 per cent
      of the root length. The corresponding value among "Smokers 1970 and 1980" was 6.0
      per cent. The difference is statistically significant (p = 0.001). In individuals
      who had given up smoking during the 10-year period (bone loss: 4.4 per cent) as
      compared with those who had smoked regularly, the progression of bone loss was
      significantly (p < 0.05) retarded. The result is in agreement with the hypothesis
      that giving up smoking produces favourable effects also with regard to the
      attachment of the teeth in the jaw-bone.

PMID- 8291031
TI  - [Pressure sores--a black heel].

PMID- 8291032
TI  - [Cross-cultural: can you fail through your attitude?].

PMID- 8291033
TI  - [Cross-cultural: an educated interpreter, thanks!. Interview by Grethe
      Kjaergaard].

PMID- 8291034
TI  - [Scissors and tweezers].

PMID- 8291035
TI  - [Nursing stories. Death of a refugee].

PMID- 8291036
TI  - [Health care--a political knowledge].

PMID- 8291037
TI  - [Home nursing--intravenous access at home].

PMID- 8291038
TI  - [Cross-professional--we are ministers to each other].

PMID- 8291039
TI  - [Negotiations 93--is it successful?].

PMID- 8291040
TI  - [Hospitalization--the acutely ill medical patient].

PMID- 8291041
TI  - [Breast feeding--we must say it together].

PMID- 8291042
TI  - [Like finding water in the desert].

PMID- 8291043
TI  - [Nursing stories. Let us call it love].

PMID- 8291044
TI  - [Project professional development. Better documentation of nursing care].

PMID- 8291045
TI  - [Education--consumers' needs].

PMID- 8291046
TI  - [Overadmission drudgery and personnel flight].

PMID- 8291047
TI  - [Work environment. French nurses are under stress].

PMID- 8291048
TI  - [Vaccination against Rhinopneumonia].

PMID- 8291049
TI  - [Air sac mycosis: topical treatment using enilconazole administered via
      indwelling catheter].
AB  - In a horse with chronic unilateral nasal discharge guttural pouch mycosis caused
      by Aspergillus fumigatus was diagnosed. A percutaneous indwelling catheter was
      surgically installed in the left guttural pouch. Initial treatment with a
      povidone iodine solution proved to be unsatisfactory. Treatment was continued by
      administering enilconazole by ways of an indwelling through-the-nose-catheter.
      The latter treatment resulted in complete recovery.

PMID- 8291050
TI  - [A female dog who grew progressively more lethargic and hoarse].
AB  - A female dog (Collie dog, eight years of age, non-spayed) was referred to the
      University Clinic for Companion Animals with signs and symptoms suggesting
      endogenous progesterone-induced acromegaly and cystic endometrial hyperplasia.
      The dog had glucose intolerance, but the growth hormone concentration in plasma
      was within the reference range. The latter was probably due to the decline of
      progesterone at the end of the luteal phase, resulting in an abrogation of the
      process of progesterone-induced growth hormone hypersecretion. After
      ovariohysterectomy the glucose-tolerance normalized.

PMID- 8291051
TI  - Acetylator genotype-dependent formation of 2-aminofluorene-hemoglobin adducts in
      rapid and slow acetylator Syrian hamsters congenic at the NAT2 locus.
AB  - Arylamine-hemoglobin adducts are a valuable dosimeter for assessing arylamine
      exposures and carcinogenic risk. The effects of age, sex, time-course, dose, and
      acetylator genotype on levels of 2-aminofluorene-hemoglobin adducts were
      investigated in homozygous rapid (Bio. 82.73/H-Patr) and slow (Bio. 82.73/H-Pats)
      acetylator hamsters congenic at the polymorphic (NAT2) acetylator locus.
      Following administration of a single ip dose of [3H]2-aminofluorene, peak 2
      aminofluorene-hemoglobin adduct levels were achieved at 12-18 hr and retained a
      plateau up to 72 hr postinjection in both rapid and slow acetylator congenic
      hamsters. 2-Aminofluorene-hemoglobin adduct levels did not differ significantly
      between young (5-6 weeks) and old (32-49 weeks) hamsters or between male and
      female hamsters within either acetylator genotype. 2-Aminofluorene-hemoglobin
      adduct levels increased in a dose-dependent manner (r = 0.95, p = 0.0001) and
      were consistently higher in slow versus rapid acetylator congenic hamsters in
      studies of both time-course and dose-effect. The magnitude of the acetylator
      genotype-dependent difference was a function of dose; 2-aminofluorene-hemoglobin
      adduct levels were 1.5-fold higher in slow acetylator congenic hamsters following
      a 60 mg/kg 2-aminofluorene dose (p = 0.0013) but 2-fold higher following a 100
      mg/kg 2-aminofluorene dose (p < 0.0001). These results show a specific and
      significant role for NAT2 acetylator genotype in formation of arylamine
      hemoglobin adducts, which may reflect the relationship between acetylator
      genotype and the incidence of different cancers from arylamine exposures.

PMID- 8291052
TI  - Radiation-induced early pulmonary endothelial ectoenzyme dysfunction in vivo:
      effect of indomethacin.
AB  - We investigated the early effects of radiation on pulmonary endothelial function
      in vivo 7-8 hr after exposure of rabbits to a single dose of 30 Gy to the chest.
      Utilizing multiple indicator-dilution techniques, we measured rates and kinetics
      of hydrolysis of the synthetic substrates [3H]benzoyl-Phe-Ala-Pro (BPAP) and
      [14C]benzoyl-Ala-Gly-Pro (BAGP) by endothelial-bound angiotensin-converting
      enzyme (ACE) and of 5'[14C]-AMP by endothelial-bound 5'-nucleotidase (NCT) and
      binding of the synthetic ACE inhibitor [3H]RAC-X-65 during a single
      transpulmonary passage in anesthetized, artificially ventilated, open-chest
      rabbits in which both systemic and pulmonary circulations were fully supported by
      an extracorporeal pump. We have shown that these techniques and the use of the
      aforementioned probes provide reliable information on pulmonary endothelial
      function in vivo. Radiation to the chest produced endothelial ectoenzyme
      dysfunction, as reflected in altered available perfused capillary surface area
      and altered enzyme kinetics of all probes (decreases in substrate hydrolysis,
      inhibitor binding, first- and second-order kinetic constants) over a wide range
      of pulmonary blood flow values (reflecting approximately 60-200% of normal
      cardiac output). Indomethacin prevented most of these alterations in partially as
      well as fully recruited lungs. We conclude that impairment of endothelial
      ectoenzyme activity is an early event in the pathogenesis of radiation-induced
      lung damage, which occurs independently of hemodynamic influences and may involve
      synthesis of arachidonic acid metabolites.

PMID- 8291053
TI  - Role of quinone reductase in in vivo ethanol metabolism and toxicity.
AB  - Quinone reductase (QR), in the presence of suitable substrate, results in the
      regeneration of NAD+ from NADH. To test the hypothesis that QR can play a role in
      ethanol metabolism and toxicity, we studied the effect of a quinone as well as of
      induced levels of QR on ethanol administered in vivo to male rats and mice.
      Butylated hydroxyanisole (BHA) is known both to induce QR and to be metabolized
      to tert-butyl quinone (TBQ). Dietary BHA (0.75% for 10 days), followed by oral
      ethanol (4 g/kg, by gavage), increased the rate of ethanol disappearance and
      decreased the area under the curve (AUC) for blood ethanol in both rats and mice.
      In addition, BHA pretreatment of rats was shown to prevent ethanol-induced 24-hr
      hepatic triglyceride accumulation. Also, in rats, TBQ (5 mg/kg, ip) led to
      decreased AUC and hepatic triglyceride accumulation, although the ethanol
      disappearance rate was not significantly affected. TBQ in BHA-fed rats resulted
      in even greater effects on the ethanol disappearance rate and AUC than TBQ or BHA
      treatment alone. None of these treatment regimens resulted in a significant
      change in volume of distribution of ethanol. Thus, these results support the
      hypothesis that induction of QR and/or administration of quinones lead to
      enhanced in vivo metabolism of ethanol and decreased hepatotoxicity.

PMID- 8291054
TI  - Pharmacokinetic interaction between benzene metabolites, phenol and hydroquinone,
      in B6C3F1 mice.
AB  - There is strong evidence that metabolites are responsible for adverse effects of
      benzene. Benzene myelotoxicity, reproduced by coadministering phenol (PH) and
      hydroquinone (HQ) but not when these benzene metabolites were administered alone,
      has been postulated to be induced by PH stimulating the myeloperoxidase-mediated
      oxidation of HQ to the toxic 1,4-benzoquinone in bone marrow. A pharmacokinetic
      interaction between PH and HQ is also hypothesized to contribute to the
      observation. Both metabolites are sulfoconjugated and glucuronoconjugated.
      Sulfoconjugation of phenolic substrates has been shown to approach saturation at
      high concentrations in rats. Thus, more PH may be converted to HQ and HQ
      conjugation may be diminished. These effects would increase the amounts of PH and
      HQ present and result (by further oxidation) in the formation of more 1,4
      benzoquinone. To test this hypothesis, we investigated the pharmacokinetics in
      blood and the recovery of hydroquinone and phenol in urine when the metabolites
      were administered intraperitoneally alone or in combination at 75 mg/kg each to
      B6C3F1 mice. The combination resulted in a 2.6-fold increase in the area under
      the blood concentration-time curve (AUC) of HQ compared to the sum of AUC values
      observed after administration of each compound alone. The half-life of HQ was
      also increased from 9 +/- 2 to 15 +/- 3 min. The AUC of PH was increased by a
      factor of 1.4. The clearance of phenol decreased from 89 +/- 13 ml/min per
      kilogram when injected alone to 62 +/- 7 ml/min per kilogram after
      coadministration. A decreased clearance of formation of each conjugate
      demonstrated that both conjugation pathways were diminished. This interaction may
      contribute to the observed production of myelotoxicity when these metabolites are
      coadministered.

PMID- 8291055
TI  - Altered expression of cytochrome P450 mRNA during chemical-induced
      hepatocarcinogenesis and following partial hepatectomy.
AB  - Levels of various cytochrome P450 proteins have been reported to be decreased to
      varying degrees in chemically induced hepatocyte nodules and following partial
      hepatectomy (PH). By screening a rat liver lambda ZAP cDNA expression library
      with antibodies raised against a partially purified preparation of cytochrome
      P450 isolated from untreated male Fischer 344 rats, we have isolated a 1.1-kb
      cDNA. This cDNA was sequenced for 139 bases from the 5' end of the sense strand
      and comparison of the resulting sequence with the sequences in Gene Man DNA data
      bank revealed 95% homology of the sequenced portion with male-specific rat
      cytochrome P450 (M-1, CYP IIC11). The 32P-labeled cDNA was used as a
      hybridization probe on RNA blots (Northern blots) prepared with total RNA from
      rat livers obtained post PH, from aflatoxin B1(AFB1)-induced rat liver tumors and
      from rat liver nodules induced with a combination of
      diethylnitrosamine/acetylaminofluorene/PH (DEN/AFF/PH). At 36 and 72 hr post PH,
      the mRNA level was decreased by > 93%. Relative to the corresponding control
      livers, the mRNA level was also decreased by 97% in the liver nodules and by 57%
      in AFB1-induced liver tumors. The RNA blots derived from the liver nodules and
      AFB1-induced liver tumors were also probed with a cDNA probe (R17) that
      recognizes other cytochromes P450 (CYP IIB1/CYP IIB2). The mRNA corresponding to
      CYP IIB1/CYP IIB2 was also depressed 92% in the nodules and 65% in the tumors.
      These results clearly indicate that the depression of both CYP IIC11 and
      IIB1/IIB2 in the hepatic nodules and the tumors is related to the inhibition of
      transcription and/or enhanced degradation of the mRNA.

PMID- 8291056
TI  - Avian embryonic brain reaggregate culture system. II. NTE activity discriminates
      between effects of a single neuropathic or nonneuropathic organophosphorus
      compound exposure.
AB  - Biochemical responses after a single exposure to either a neuropathic or a
      nonneuropathic organophosphorus compound (OP) were compared using chick embryonic
      brain cell reaggregates. Ten-day-old chick embryo brains were dissociated and
      then reaggregated and maintained in a chemically defined, serum-free medium
      without antibiotics. Seven days later, these cultures were treated for 20 min
      with either neuropathic diisopropyl phosphorofluoridate (DFP, 10(-4) M) or
      nonneuropathic paraoxon (10(-6) M). Reaggregates were assayed for
      acetylcholinesterase (ACHE), neuropathy target esterase (NTE), and 2',3'-cyclic
      nucleotide 3'-phosphodiesterase (CNP) activities for up to 32 days after
      exposure. These enzymes were examined due to inhibition of activity as a result
      of acute OP toxicity (ACHE) or delayed toxicity (NTE, CNP). DFP inhibited > 95%
      of NTE activity immediately after exposure. By Postexposure Day 2, NTE specific
      activity was 22% of untreated activity but was similar to the untreated group
      levels by Postexposure Day 7. Paraoxon exposure did not affect NTE activity. Both
      paraoxon and DFP inhibited > 99% of ACHE activity immediately after exposure. By
      Postexposure Day 2, ACHE specific activity in paraoxon-exposed cultures had
      recovered while ACHE remained 56% inhibited in DFP-exposed cultures. Both
      paraoxon- and DFP-exposed cultures recovered ACHE activity immediately following
      OP exposure if treated postexposure with an oxime reactivator, 2-pralidoxime. CNP
      specific activity was not affected by either paraoxon or DFP. These results
      demonstrated distinct differences in reaggregate NTE and ACHE activities after
      single exposure to neuropathic DFP and nonneuropathic paraoxon similar to those
      in avian in vivo assays.

PMID- 8291057
TI  - Construction of Syrian hamster lines congenic at the polymorphic
      acetyltransferase locus (NAT2): acetylator genotype-dependent N- and O
      acetylation of arylamine carcinogens.
AB  - Congenic Bio. 1.5/H-NAT2 Syrian hamster lines were constructed by introducing the
      NAT2r gene from MHA/SsLak inbred hamsters into a background BIO 1.5 Syrian inbred
      hamster line. Genetic identity of the Bio. 1.5/H-NAT2 congenic lines and
      nonidentity with the previously constructed Bio. 82.73/H-Pat congenic lines were
      determined by "DNA fingerprints" of genomic DNA derived from the different
      hamster lines. The N-acetylation capacity of the Bio. 1.5/H-NAT2 congenic hamster
      lines was clearly NAT2-dependent both in vivo and in vitro, with highest levels
      expressed in Bio. 1.5/H-NAT2r homozygous rapid acetylators, intermediate levels
      in Bio. 1.5/H-NAT2r/NAT2s heterozygous acetylators, and lowest levels in Bio.
      1.5/H-NAT2s homozygous slow acetylators. The NAT2-dependent expression of N
      acetyltransferase activity was evident toward p-aminobenzoic acid, 4-aminophenol,
      2-aminofluorene, 4-aminobiphenyl, beta-naphthylamine, and 3,2'-dimethyl-4-amino
      biphenyl in liver, kidney, colon, lung, and urinary bladder cytosols. The
      polymorphic acetyltransferase (NAT2) and the monomorphic acetyltransferase (NAT1)
      were isolated from hepatic cytosols and tested separately for their ability to
      catalyze arylamine N-acetyltransferase and N-hydroxyarylamine O-acetyltransferase
      activities. Both arylamine N-acetylation and N-hydroxyarylamine O-acetylation
      were clearly acetylator genotype-dependent when catalyzed by NAT2, and both were
      clearly acetylator genotype-independent when catalyzed by NAT1. NAT2/NAT1
      activity ratios varied with the particular arylamine substrate acetylated. These
      studies show an important role for NAT2 acetylator genotype in Syrian hamster
      carcinogenic arylamine metabolism and confirm its role in the metabolic
      activation of N-hydroxyarylamines. The Bio. 1.5/H-NAT2 congenic lines provide a
      new model for investigating the precise role of the NAT2 gene locus in arylamine
      metabolism and toxicity.

PMID- 8291058
TI  - Methylene dianiline hepatotoxicity is not leukocyte-dependent.
AB  - Methylene dianiline (DDM) causes a dose- and time-dependent cholestasis, bile
      ductular epithelial injury, and hepatic parenchymal insult in rats. The mechanism
      of toxicity is unknown. Since hepatic leukocyte infiltration is a prominent
      feature of DDM-induced liver injury, and because leukocytes play a causal role in
      hepatic and extrahepatic tissue injury, we tested the hypothesis that toxicity
      caused by DDM is dependent on neutrophils or other circulating inflammatory
      cells. A polyclonal antibody (NAb) against rat neutrophils was used to address
      the role of the neutrophil in DDM-induced liver injury. NAb administration caused
      a significant reduction in circulating neutrophils without altering other
      leukocyte numbers. Moreover, NAb pretreatment prevented hepatic neutrophil
      infiltration after administration of DDM. However, neutrophil depletion did not
      afford protection from DDM-induced liver injury. This result was confirmed and
      the role of other circulating leukocytes was evaluated by inducing systemic
      leukopenia using cyclophosphamide (CYCLO). Administration of CYCLO diminished the
      number of circulating leukocytes within 4 days after treatment. Depletion of
      leukocytes by CYCLO prevented the hepatic accumulation of leukocytes but did not
      protect rats from DDM hepatotoxicity. These results suggest that the large
      numbers of leukocytes that infiltrate the liver after DDM administration do not
      contribute to hepatic injury.

PMID- 8291059
TI  - Early responses of the liver of B6C3F1 mice to the hepatocarcinogen oxazepam.
AB  - Oxazepam has recently been shown to induce hepatocarcinogenicity in B6C3F1 mice.
      Due to the widespread human exposure to this anxiolytic compound and other
      structurally similar benzodiazepines, we conducted toxicity and cell
      proliferation studies on oxazepam to determine possible mechanisms whereby this
      nonmutagenic chemical may have exerted a carcinogenic effect. Male B6C3F1 mice
      (10 per dose-time group) received diets containing oxazepam at 0, 25, 125, 2500,
      and 5000 ppm. Mice were treated for 15, 30, 45, or 90 days, at which time they
      were evaluated for feed consumption, liver/body weight ratios, clinical
      pathology, serum oxazepam levels, and histopathology of the liver. During the
      final 7 days before sacrifice, the mice were exposed to BrDU via osmotic minipump
      to quantify hepatocellular replicative DNA synthesis. Few effects were observed
      resulting from chronic exposure to oxazepam other than statistically significant,
      dose-related increases in liver/body weight ratios. Replicative DNA synthesis was
      significantly increased in a dose-related manner at the 15-day time point in the
      125, 2500, and 5000 ppm dose groups, and attained levels of four- to five-fold
      above control levels which returned to control levels by 30 days. The lack of
      significant toxicity, sustained increased liver/body weight ratios, and the rapid
      and transient induction of replicative DNA synthesis are similar to the effects
      reported for exposure to another widely used therapeutic agent shown to be a
      nongenotoxic carcinogen, phenobarbital.

PMID- 8291060
TI  - Reversal of saxitoxin-induced cardiorespiratory failure by a burro-raised alpha
      STX antibody and oxygen therapy.
AB  - Reversal of saxitoxin (STX; 10 micrograms/kg, ip) induced cardiorespiratory
      effects by oxygen ventilation and burro-raised alpha-STX antitoxin (60 mg/kg,
      i.v.) was studied in urethane-anesthetized guinea pigs acutely instrumented for
      concurrent monitoring of medullary respiratory-related single units, diaphragm
      EMG, Lead II electrocardiogram, arterial blood pressure (BP), arterial pH, and
      O2/CO2 tensions, electrocorticogram (ECoG), and end-tidal CO2. STX-induced
      cardiorespiratory effects included (1) a state of progressive bradypnea and
      hypercapnia; (2) a functional blockade of the diaphragm; (3) a prolongation of
      respiratory cycle duration; (4) an aberrant bulbar respiratory-related neuronal
      activity pattern; and (5) a decline in BP and heart rate. The therapeutic effect
      of artificial ventilation following STX-induced apnea was equivocal in that the
      cardiorespiratory activities, be they of central or peripheral nature, remained
      dysfunctional despite continued oxygen ventilation. Spontaneous breathing and
      cardiovascular performance following STX-induced apnea could all be promptly
      restored (typically in less than a minute) by combined oxygen/antitoxin therapy.
      Notable also was a state of uncompensated acidemia (as revealed by changes in
      arterial pH and CO2 tension) which persisted throughout the course of therapeutic
      intervention. Notwithstanding, the ventilatory frequency continued to be low, the
      central respiratory activity pattern remained aberrant, and the ECoG amplitudes
      were still depressed. In consideration of these findings, and of the large
      molecular weight of alpha-STX antitoxin (> 150,000 Da) which limits its entry
      into the CNS, we are of the opinion that the therapeutic effects of antitoxin are
      probably confined primarily to the periphery.

PMID- 8291061
TI  - Chromodacryorrhea in rats: absence following soman poisoning.
AB  - Chromodacryorrhea is the secretion of so-called "bloody tears" from the harderian
      gland which nearly circumscribes the eye within the bony orbit. Direct-acting
      cholinergic agonists such as oxotremorine, carbachol, and pilocarpine caused
      chromodacryorrhea but nicotine did not. Atropine blocked chromodacryorrhea
      induced by systemic administration of direct-acting cholinergic agonists. Thus,
      chromodacryorrhea appears to be a muscarinic receptor-related event. Soman
      (pinacolyl methylphosphonofluoridate), a potent irreversible inhibitor of
      acetylcholinesterase which increases the synaptic concentration of the
      neurotransmitter acetylcholine, did not induce chromodacryorrhea in rats.
      Similarly, physostigmine, a tertiary, carbamate acetylcholinesterase inhibitor,
      did not induce chromodacryorrhea. In vivo soman-induced inhibition of harderian
      gland acetylcholinesterase was independent of the soman dose and the inhibition
      was significantly less than brain acetylcholinesterase. In vitro soman-induced
      inhibition of harderian gland acetylcholinesterase was not significantly
      different from that of diaphragm acetylcholinesterase. The lack of inhibition of
      acetylcholinesterase in the harderian gland does not appear to be due to a
      difference in sensitivity to inhibition by soman. The distribution of the various
      molecular forms of acetylcholinesterase between the diaphragm and harderian gland
      was different. There was a great deal more of the 4S form of acetylcholinesterase
      in the harderian gland than in the diaphragm. The lack of the following,
      inhibition of harderian gland acetylcholinesterase and elevation of the synaptic
      concentration of acetylcholine, could explain the absence of chromodacryorrhea
      following soman poisoning. The discrepancy between the significant soman-induced
      inhibition of brain acetylcholinesterase and the lack of inhibition of harderian
      gland acetylcholinesterase allows one to speculate that there may be a very
      efficient scavenger of soman present in the rat harderian gland.

PMID- 8291062
TI  - Metabolism of 3,3'-iminodipropionitrile and deuterium-substituted analogs:
      potential mechanisms of detoxification and activation.
AB  - 3,3'-Iminodipropionitrile (IDPN), a neurotoxicant that causes an excitatory CNS
      syndrome and a proximal axonopathy, is metabolized to beta-aminopropionitrile
      (BAPN), cyanoacetic acid (CAA), and beta-alanine (beta-ala) in rats. None of
      these metabolites are neurotoxic, suggesting that they are products of
      detoxification. To investigate potential pathways of activation and
      detoxification, we treated groups of rats with saline, IDPN, or deuterium
      substituted analogs, 2,2,2',2'-tetradeuterio-IDPN (2-d-IDPN) or 3,3,3',3'
      tetradeuterio-IDPN (3-d-IDPN) at 3 mmol/kg/day for 3 days. beta-Alanine was
      isolated from urine by ion-exchange chromatography and analyzed by GC-MS and
      HPLC. The position of the deuterium labels on beta-ala indicates that beta-ala is
      derived by hydrolysis of IDPN and that the carboxylate of beta-ala is derived
      from the nitrile of IDPN. Excretion of CAA, measured by GC-MS, is markedly
      reduced in 3-d-IDPN-treated rats. Since 3-d-IDPN is more potent than equimolar
      doses of IDPN, the diminished excretion of CAA may be due to an isotopic effect
      in retarding the hydrolysis of IDPN to BAPN and CAA. The finding that 2-d-IDPN is
      less potent than IDPN suggests that activation of IDPN may occur near the 2
      position. Although nitrile hydrolysis is established, the mechanism is not yet
      clear.

PMID- 8291063
TI  - The cyanide-metabolizing enzyme rhodanese in different parts of the respiratory
      systems of sheep and dog.
AB  - Studies on the rhodanese activity of respiratory systems of sheep and dog showed
      that a significant difference exists in the pattern of distribution of this
      enzyme in different parts of the respiratory system of both species. In sheep,
      larynx, trachea, bronchiole, and lung contain higher activity than nasal cavity
      and pharynx. In dog, significantly greater rhodanese activity was found in nasal
      cavity than in other parts of the respiratory system. In regions with high
      rhodanese activity the enzyme was more concentrated in the mucosa than in the
      underneath tissues. These results are discussed in terms of the possible role of
      rhodanese in cyanide metabolism in respiratory tract and the efficacy of this
      organ in inhaled cyanide detoxification in these species of animals.

PMID- 8291064
TI  - Activation of human monocytes with lipopolysaccharide induces metallothionein
      expression and is diminished by zinc.
AB  - The metal-binding protein metallothionein (MT) confers resistance to the toxic
      effects of metals. Although a role for MT in metal homeostasis and protection
      against toxic free radicals has been suggested, no clear physiological function
      has been established. The ability of human monocytes to be activated by bacterial
      lipopolysaccharide (LPS) treatment provided a model to investigate the effect of
      zinc on both cellular activation (H2O2 production) and MT expression. In both
      primary human monocytes and a monocyte-derived cell line (THP-1), LPS induced
      activation and MT expression; it did not induce MT expression in nonmonocyte
      human cells. Treatment of THP-1 cells with nontoxic zinc levels increased MT
      accumulation. Subsequent treatment with LPS resulted in a decrease in both MT
      mRNA and protein levels and inhibited the ability of THP-1 cells to undergo the
      respiratory burst. Pretreatment with cadmium had the same inhibitory effect. We
      conclude that MT expression is associated with monocyte activation, and exposure
      to zinc or cadmium interferes with the ability of monocytes to respond to
      activation signals. Metallothionein may play a role in that response.

PMID- 8291065
TI  - Dose-response relationships in mice following subchronic exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin: CYP1A1, CYP1A2, estrogen receptor, and protein
      tyrosine phosphorylation.
AB  - The dose-response relationships for different endpoints in different tissues were
      compared in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment.
      TCDD was administered 5 days a week for 13 weeks at doses ranging from 1.5 to 150
      ng/kg/day to female B6C3F1 mice. Ethoxyresorufin-O-deethylase (EROD) activity, a
      marker for CYP1A1, was increased in liver, lung, and skin at doses as low as 1.5
      ng/kg/day. EROD activity did not attain maximal induction. Liver acetanilide-4
      hydroxylase activity, a marker for CYP1A2, was significantly induced at 1.5
      ng/kg/day and reached maximal induction at 45 ng/kg/day. TCDD treatment
      significantly increased the amount of phosphorylated forms of three
      phosphotyrosyl proteins (pp32, pp34, and pp38) in liver S-20 fractions. Changes
      in these phosphotyrosyl proteins occurred at 1.5 ng/kg/day and reached maximal
      induction at 4.5 ng/kg/day. No changes in phosphotyrosyl proteins were observed
      in skin. Hepatic and uterine estrogen receptor levels were not altered at any of
      the doses tested. These data indicate that induction of CYP1A1, CYP1A2, and the
      increases in phosphorylated forms of pp32, pp34, and pp38 are sensitive
      indicators of TCDD exposure. The dose-response curves for increases in CYP1A1,
      CYP1A2, and phosphorylated pp32, pp34, and pp38 in liver were different from each
      other. TCDD produces multiple effects with multiple dose-response curves
      suggesting that there are events in addition to receptor binding that are
      endpoint specific, leading to different dose-response relationships.

PMID- 8291066
TI  - Assay of pulmonary microvascular endothelial angiotensin-converting enzyme in
      vivo: comparison of three probes.
AB  - We monitored the activity of pulmonary microvascular endothelial-bound
      angiotensin-converting enzyme (ACE) in vivo by means of multiple indicator
      dilution-type techniques, utilizing three different probes: the hydrolysis of two
      substrates, [3H]-benzoyl-Phe-Ala-Pro (BPAP) and [14C]benzoyl-Ala-Gly-Pro (BAGP),
      and the binding of the inhibitor [3H]RAC-X-65 (RAC), all measured during a single
      transpulmonary passage in anesthetized rabbits, placed on total heart bypass, so
      that both systemic and pulmonary circulations were fully supported by means of a
      two-channel extracorporeal pump. Experiments were performed at pulmonary blood
      flows (Qb) of 250, 400, 560, and 800 ml/min in control or indomethacin-pretreated
      rabbits. ACE activity was also compared to that of pulmonary microvascular
      endothelial-bound 5'-nucleotidase, by measuring the dephosphorylation of its
      natural substrate 5'-[14C]AMP. We calculated substrate utilization, mean lung
      transit time (t), and volume of distribution (i.e., central blood volume) of all
      substrates, as well as inhibitor binding. We also calculated Amax/Km and Bmax
      products of enzyme mass and kinetic constants for substrates and inhibitor,
      respectively. As Qb increased, Amax/Km values for all three substrates and Bmax
      increased linearly, indicating microvascular recruitment. In experiments in which
      either BPAP and 5'-AMP metabolism or BAGP metabolism and RAC binding were studied
      concomitantly, a linear relationship was observed between Qb-induced changes in
      Amax/Km values of BPAP vs 5'-AMP as well as in Amax/Km of BAGP vs Bmax of RAC.
      Similarly, increasing Qb increased central blood volume and decreased t.
      Indomethacin had no effect on most of the hemodynamic or enzyme parameters
      measured. We conclude that in vivo assays of ACE proceed as predicted by
      Michaelis-Menten kinetics and offer insights into pulmonary endothelial
      pathophysiology.

PMID- 8291067
TI  - S-(1,2-dichlorovinyl)-3-mercaptopropionic acid effects on renal function and
      ultrastructure in pentobarbital-anesthetized dogs: site-specific toxicity and
      evidence for its toxification via the pathway responsible for beta-oxidation of
      fatty acids.
AB  - S-(1,2-dichlorovinyl)-3-mercaptopropionic acid (DCV-3-MPA) was equally
      nephrotoxic to spontaneously-respiring and mechanically-ventilated, pentobarbital
      anesthetized dogs. Its nephrotoxicity was expressed as dose-dependent changes in
      key renal function parameters, in proximal tubular S1, S2 and S3 cellular
      architecture and in the ability of the kidneys to respond maximally to ethacrynic
      acid, an efficacious loop diuretic. The nephrotoxicity associated with DCV-3-MPA
      was not the result of extrarenal actions such as hypoxemia and subsequent renal
      tissue hypoxia because mechanical ventilation was not protective. Four lines of
      evidence suggested that DCV-3-MPA was taken-up by renal proximal tubular cells
      like a fatty acid and metabolized by the mitochondrial beta-oxidation pathway to
      a reactive nephrotoxic intermediate: (i) probenecid pretreatment, which reduces
      the renal uptake of many organic anions but fails to do so with anions of fatty
      acids, failed to modify the nephrotoxicity of DCV-3-MPA; (ii) the next higher and
      lower homologues of DCV-3-MPA (i.e., S-(1,2-dichlorovinyl)-4-mercaptobutanoic
      acid (DCV-4-MBA) and S-(1,2-dichlorovinyl)-mercaptoacetic acid (DCV-MAA)) cannot
      yield the same reactive intermediate as DCV-3-MPA upon beta-oxidation and neither
      was nephrotoxic; (iii) DCV-MAA was found in plasma and urine following
      administration of DCV-4-MBA and (iv) the renal mitochondria were reproducibly
      damaged by DCV-3-MPA whereas the peroxisomes, which are also capable of
      performing beta-oxidation of certain fatty acids, were unscathed.

PMID- 8291068
TI  - Stress protein synthesis induced by cadmium-cysteine in rat kidney.
AB  - Biomarkers are important tools which enable toxicologists to reliably predict and
      detect exposures to xenobiotics and resultant cell injury, ultimately improving
      risk assessments. Since the de novo synthesis of stress proteins can be detected
      early after exposure to some agents, analysis of toxicant-induced changes in gene
      expression, i.e. alterations in patterns of protein synthesis, may be useful to
      develop as biomarkers of exposure and toxicity. We are utilizing various
      xenobiotics as tools to study stress protein synthesis in target organs in order
      to evaluate the target tissue-specificity of this response. Previous data from
      this laboratory have demonstrated that induction of stress proteins in rat liver,
      but not kidney, after acute exposure to CdCl2 precedes hepatoxicity. Since kidney
      is a target tissue after chronic Cd exposure, it was of interest to examine
      stress protein synthesis in this tissue. However, dose-limiting hepatotoxicity
      precluded this evaluation. Cd complexed with molecules such as cysteine (cys) or
      metallothionein has been used in acute dosing regimens as a tool in order to
      study the nephrotoxicity of Cd. Therefore, this study was undertaken in order to
      evaluate Cd-induced stress protein synthesis in an important tissue known to be
      injured after chronic exposure, i.e. kidney. Specific objectives included
      comparing stress protein synthesis in rat kidney and liver after acute exposure
      to Cd-cys and CdCl2, determining the Cd threshold concentration for renal stress
      protein synthesis and assessing the relationship between stress protein synthesis
      and nephropathy. Male rats were exposed to equivalent doses of Cd as CdCl2 or Cd
      cysteine (molar ratio Cd:cys = 1:15). Kidney Cd concentrations increased 5-fold
      after i.v. injection of Cd-cys compared to CdCl2, mimicking Cd distribution
      following chronic exposure. After exposure to Cd, tissue slices were incubated
      with 35S-methionine. Slices were subsequently homogenized and centrifuged, and
      the 16,000 g supernatants were subjected to SDS-polyacrylamide gel
      electrophoresis. Proteins which had incorporated 35S-methionine were detected by
      autoradiography. De novo synthesis of 70, 90 and 110 kDa proteins was enhanced in
      liver, but not in kidney, 4 h after injection of 2 mg Cd/kg as CdCl2. In
      contrast, dose-related increases in synthesis of these proteins were observed in
      kidney 4 h after injection of 1 and 2mg Cd/kg as Cd-cys, but not at lower
      dosages. In addition, synthesis of a 68 kDa kidney protein was inhibited at 2 mg
      Cd/kg as Cd-cys. The threshold for Cd-induced stress protein synthesis was shown
      to be between 4 and 8 micrograms Cd/g tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8291069
TI  - A digitized fluorescence imaging study of intracellular free calcium,
      mitochondrial integrity and cytotoxicity in rat renal cells exposed to ionomycin,
      a calcium ionophore.
AB  - The objective of this study was to explore the role of extracellular Ca2+ and
      mitochondrial integrity in ionomycin-induced cytotoxicity in primary cultures of
      rat kidney cortical epithelial cells using digitized fluorescence imaging (DFI),
      which is a powerful tool for continuously observing the dynamic intracellular
      biochemistry of single living cells. Using DFI, intracellular free calcium ion
      concentration ([Ca2+]i), mitochondrial membrane potential and loss of cell
      viability in individual rat renal cortical epithelial cells were examined
      temporally by fura-2, rhodamine 123 (Rh-123) and propidium iodide (PI),
      respectively. Images were taken within 10 min after exposure to 5 and 10 microM
      ionomycin. These three parameters, [Ca2+]i, mitochondrial membrane potential and
      cell viability, were also measured in populations of cells by a multiwell
      fluorescence scanner with fluo-3, Rh-123 and PI, respectively. Cytotoxicity was
      also assessed by two colorimetric cytotoxicity tests (LDH leakage and
      mitochondrial MTT reduction). Using DFI, the fluorescence scanner and the
      colorimetric cytotoxicity tests, we found that exposure of primary cultures of
      rat kidney cortical epithelial cells to high concentrations of ionomycin (5 and
      10 microM) caused a rapid and sustained rise in [Ca2+]i, which preceded
      dissipation of the mitochondrial membrane potential and loss of cell viability
      and that chelation of extracellular Ca2+ with EGTA attenuated these responses. We
      demonstrated the value of using DFI to continuously observe the dynamic
      intracellular biochemistry of single living cells by establishing a sequence of
      elevated [Ca2+]i, dissipation of mitochondrial membrane potential and
      cytotoxicity. We conclude that a combination of the influx of extracellular Ca2+
      and loss of mitochondrial integrity may be responsible for the cytotoxicity
      observed in individual renal cells and populations of renal cells after treatment
      with ionomycin.

PMID- 8291070
TI  - Induction of serum-borne immunomodulatory factors in B6C3F1 mice by carbon
      tetrachloride. I. Carbon tetrachloride-induced suppression of helper T-lymphocyte
      function is mediated by a serum borne factor.
AB  - Following carbon tetrachloride-induced liver injury, hepatotrophic factors are
      synthesized and released into the serum to facilitate the regeneration of damaged
      hepatic tissue. We investigated the possibility that immunosuppression could be
      mediated through induction of a serum factor(s) because in vivo exposure of
      B6C3F1 mice to carbon tetrachloride selectively inhibits T-cell-dependent immune
      responses. Addition of mouse serum (5% by volume) obtained from mice treated with
      carbon tetrachloride (250 or 500 mg/kg/day for 7 days) to naive spleen cell
      cultures markedly suppressed the sheep red blood cell antibody-forming cell
      response compared to controls (P < 0.01). Immunosuppression was observed in mice
      sensitized with sheep red blood cells 48 h, but not 24 or 72 h, following one
      dose of carbon tetrachloride (1000 mg/kg). Only serum isolated from mice 48 h
      following exposure to a single dose of carbon tetrachloride (1000 mg/kg)
      suppressed the antibody-forming cell response when added in vitro to spleen cell
      cultures. Biodistribution studies using [14C]-labelled carbon tetrachloride
      demonstrated that accumulation of the [14C]-label was primarily associated with
      excretory organs (liver, kidneys and lungs) but not with the serum, red blood
      cells, or spleen. Surprisingly, 24 and 48 h following exposure to [14C]-labelled
      carbon tetrachloride, an increase in radioactivity was detected in the thymus.
      The distinct profile of immunosuppressive activity associated with serum isolated
      from carbon tetrachloride-treated mice and the biodistribution studies clearly
      demonstrating a negligible amount of carbon tetrachloride or metabolites in the
      serum strongly implicate the role of a carbon tetrachloride-induced serum borne
      immunosuppressive factor.

PMID- 8291071
TI  - Laughter and stress management in the OR.
AB  - 1. The United States spends approximately $23 billion per year treating stress
      related illnesses. Stress-related injuries comprise 15% of all occupational
      stress-related illnesses. 2. When stress is relieved, workers may use less sick
      time, OR departments may stem the tide of staff turnover, and nurses may improve
      interpersonal relations with other staff members and surgeons. 3. Humor shifts
      perspective, diffuses tensions/confrontations, conveys a complicated message
      concisely, increases flexibility, raises energy levels, wards off criticism, and
      builds a cohesive team unit.

PMID- 8291072
TI  - Seriously, laughter matters.
AB  - 1. There is a humor-health connection; humor is related to wellness and holistic
      health. Humor and humor skills are becoming increasingly valued assets in the
      work place. 2. The use of humor among co-workers and administrators serves to
      form a more cohesive unit and combats the inherent stress in the demanding health
      care environment. Finding common experiences and frustrations, and reinterpreting
      them as a group, develops a camaraderie and power over previously difficult
      situations. 3. Humor and laughter can help us in the workplace and in our
      personal lives. After you put humor and laughter into your own life, you can take
      these skills to your patients. You can show them how to use mirth and silliness
      to live life on life's terms or, said another way, to thrive in adversity by
      accessing joy in absurdity.

PMID- 8291073
TI  - Nurse clowns in the OR. An interview with Barbara Ann D'Anna.
AB  - 1. There is always some degree of stress in the OR. The trick is to play up the
      eustress (positive, motivating energy) and alleviate the distress
      (negative/draining energy). Eustress is characterized by smiles, chatter,
      purposeful movement, and an OR that hums with efficiency. Distress can be
      assessed by unhappy faces, loud grumbling, dragging feet, and an OR that grinds
      to a halt. 2. Humor relaxes people and situations. It allows creative juices to
      flow and enhances what people take away from meetings by facilitating the
      creative process. The staff members feel good about themselves and what they are
      doing, and they become more productive. 3. The OR can be both a wonderful
      (eustress) and a horrible (distress) place in which to work. We need to savor the
      wonderful--and season the horrible with humor to make it palatable. As directors
      use humor to reduce staff stress levels, they should remember to bring laughter
      and humor into their own lives as well.

PMID- 8291074
TI  - Congenital clubfoot.
AB  - 1. Clubfoot is more common in males and 50% of cases are bilateral. 2. Contact
      and reassurance with the parents is important during a lengthy procedure, such as
      bilateral club foot releases. 3. Edema is the most common complication of
      clubfoot repair, so it is important to monitor the infant closely postoperatively
      for circulatory problems.

PMID- 8291075
TI  - Controlling infection potentials when passing surgical instruments.
AB  - 1. Recent research suggests that percutaneous injury occurs in 6.9% of observed
      surgical procedures. This finding indicates that percutaneous injuries occur
      often during surgery, placing OR personnel at risk for infection potential with
      bloodborne pathogens. 2. One approach to reducing the risk of injury with
      contaminated sharps is to introduce a change in the normal method of passing
      sharps. A new method, the "hands-free" technique, focuses on the safety of the OR
      professional without disrupting the established routine of the operating room.
      This new technique is designed to reduce the number of "collisions" between
      sharps and OR professionals. 3. Caution and staff education are important during
      any attempt to use hands-free instrument passing techniques in an OR setting. The
      hands-free technique of passing sharps should be practiced until all members of
      the surgical team have a high degree of comfort using it.

PMID- 8291076
TI  - The right to die or choosing not to live--a dilemma.

PMID- 8291077
TI  - Special focus on humor in the OR.

PMID- 8291078
TI  - How to lead and manage employees.
AB  - Events are managed and people are led. In the people-oriented society of today,
      good managers must also be good leaders. A manager who ignores using techniques
      that focus on the needs of employees will soon find a large gap between what the
      leader desires and what the employees will do. An approach that communicates
      positive regard for others, enthusiastic role modeling, participative management,
      and a vision that is constantly held imminent will enable the nurse to lead.

PMID- 8291079
TI  - The purpose and function of humor in OR nursing.
AB  - 1. Laughter has always echoed throughout the halls and rooms of hospitals. The
      latest jokes and the funniest stories are heard in the OR department; from there
      come some of the funniest "dumb student" stories; macabre practical jokes;
      stories and jokes about surgeon/anesthesiologist/nurse relationships; and jokes,
      cartoons, and get-well cards that reveal patients' greatest anxieties and fears
      about surgery and the operating room. 2. Humor as an indirect form of
      communication (verbal or non-verbal) has many sociologic and psychologic
      purposes. Also, humor enhances learning, and stimulates alertness and creativity.
      The resulting laughter produces a positive physiologic change in the body. 3.
      Humor and laughter are healthy therapeutic tools we must value, learn to
      cultivate, and add to our professional and personal lives. However, there is
      still a need for more research on how to use humor therapeutically, especially in
      OR nursing.

PMID- 8291080
TI  - Can homologous proteins evolve different enzymatic activities?

PMID- 8291081
TI  - The concept of biochemical organization.

PMID- 8291082
TI  - rRNA-mRNA complementarity: implications for translation initiation.

PMID- 8291083
TI  - Capillary electrophoresis: pioneering new approaches for biomolecular analysis.
AB  - There is little doubt that electrophoretic techniques have made an immeasurable
      contribution to our understanding of biochemical systems. Capillary
      electrophoresis (CE), the subject of this article, is not yet as widely utilized
      as 'slab' gel electrophoresis for the separation of biological molecules, but may
      confer several advantages over more conventional techniques. For example, it
      offers fast separation, needs only minute quantities of sample, gives high
      quantitative reproducibility and can be automated. These qualities make it a
      highly attractive method, which will ultimately lead to new horizons for
      biomolecular analyses.

PMID- 8291084
TI  - Why do thylakoid membranes from higher plants form grana stacks?
AB  - Chloroplasts contain a system of membrane sacs, the thylakoids, some of which are
      stacked to form grana (singular, granum), whereas others float freely in the
      stroma. It is on the thylakoid membranes that the electron carriers necessary for
      photosynthesis reside. There has been continuous speculation and discussion about
      the function of the grana ever since Menke postulated their lamellar nature in
      1939. On the basis of new insights into the biophysics of the two photosystems
      and the molecular organization of thylakoid membranes of algae that exhibit a
      different lateral heterogeneity from that of higher plants, we propose that the
      membrane stacking found in the chloroplasts of higher plants and green algae is
      just one way in which Nature implements a general principle, namely that of
      physically separating a slow (PS II) and a fast (PS I) photosystem.

PMID- 8291085
TI  - RecA belongs among the MC-DBPs.

PMID- 8291086
TI  - NOGGIN is unlikely to be homologous to the Kunitz protease-inhibitor family.

PMID- 8291087
TI  - Unique sequence repeats in the alpha-subunit of protein farnesyltransferases.

PMID- 8291088
TI  - PMP47, a peroxisomal homologue of mitochondrial solute carrier proteins.

PMID- 8291089
TI  - Regulation of translation initiation and modulation of cellular physiology.
AB  - Translational control of gene expression is an important regulatory mechanism in
      cellular physiology. In eukaryotes, ribosomes can initiate translation by two
      different mechanisms: a majority of mRNAs undergo cap-dependent initiation at
      their extreme 5'-ends, but initiation can occur internally in some mRNAs. A
      number of important cellular responses, such as entry into a proliferative state
      and adaptation to changing nutrient levels, are mediated by changes in the
      mechanism of translation initiation of specific mRNAs. This article discusses new
      insights into control of gene expression gained through studies of regulation of
      eukaryotic translational initiation.

PMID- 8291090
TI  - DNA damage and the DNA-activated protein kinase.
AB  - DNA-activated protein kinase (DNA-PK) is a nuclear serine/threonine protein
      kinase that is activated in vitro by DNA fragments. The cellular targets of DNA
      PK are nuclear, DNA-binding, regulatory proteins including Sp1, Fos, Jun, Myc,
      the tumor suppressor protein p53, and RNA polymerase II. These characteristics
      suggest a role for DNA-PK in coordinating nuclear processes and as a modulator of
      checkpoint mechanisms activated by DNA damage.

PMID- 8291091
TI  - Reactive species and their accumulation on radical-damaged proteins.
AB  - Hydroperoxides and catechols are described as novel reactive products of radical
      attack on proteins. These species, like other components of oxidized and
      otherwise damaged proteins, may accumulate in some biological systems. We propose
      that the reactive species may then attack other biomolecules, and constitute both
      a marker and a mechanism of age-related pathologies.

PMID- 8291092
TI  - Methods and reagents.

PMID- 8291093
TI  - Contributing software to the internet: the Amplify program.

PMID- 8291094
TI  - Xenotransplant-associated zoonoses. Strategies for prevention.

PMID- 8291095
TI  - Further studies of veto activity in rhesus monkey bone marrow in relation to
      allograft tolerance and chimerism.
AB  - Infusing the DR-/dim fraction of bone marrow cells (BMC) from an allogeneic
      kidney donor into rabbit antithymocyte globulin-treated transplant recipients
      delivers a tolerogenic signal, leading to functional allograft tolerance in
      rhesus monkeys without additional drug therapy. Our updated results in an
      expanded series show a median 131-day graft survival of recipients given DR-/dim
      donor BMC with a 23% 1-year survival (P < 0.00001 vs. rabbit antithymocyte
      globulin controls). Removing DRbright cells from donor BMC appeared to have a
      significant effect (P < 0.05). We have further investigated the tolerogenic
      mechanism within the experimental framework of the veto hypothesis in this
      preclinical model. In limiting dilution assays, we demonstrated the donor
      specificity of clonal inactivation of CTL precursors (CTLp) after in vitro or in
      vivo exposure to DR-/dim donor BMC, confirming specific tolerance. Additionally,
      in vitro studies confirmed the allogeneic specificity of CTLp inactivation in 3
      cell MLR assays; minimal bystander effects were seen on normal CTLp responses to
      third party stimulator cells, while CTLp responses to the BMC donor's cells were
      abrogated in the same cultures. BMC mediating the veto effect were found to be
      resistant to L-leucyl-L-leucine methyl ester (Leu-leu-OMe), which excluded BMC
      mediated cytotoxicity by NK or lymphokine-activated killer cells, CTL, or
      activated macrophages. In contrast, veto activity was abolished if the BMC were
      pretreated with either high dose UV-B light irradiation, mitomycin, or gamma
      irradiation, indicating that BMC contained a UV-B-sensitive precursor of the veto
      effector, and that a proliferative step separated the two. Irradiation of DR-/dim
      donor BMC or administration of cyclophosphamide after infusion of nonirradiated
      BMC prevented the tolerogenic effect. Only recipients given nonirradiated DR-/dim
      donor BMC demonstrated PBL chimerism, which associated with functional deletion
      of antidonor CTLp and duration of graft survival. The Leu-leu-OMe resistance and
      the other properties of the allogeneic monkey CD3- CD2+ CD8+ BMC subpopulation
      that exhibits tolerance-promoting activity in vitro and in vivo lead us to
      postulate that a donor BMC-derived precursor population, possibly a dendritic
      cell population, may induce allogeneic unresponsiveness in this model.

PMID- 8291096
TI  - Alloantigenicity of human endothelial cells. II. Analysis of interleukin 2
      production and proliferation by T cells after contact with allogeneic endothelia.
AB  - In organ allograft recipients, the first point of contact between the host immune
      system and the graft alloantigens is the graft vascular endothelia. Our previous
      experiments have established that there are multiple pathways by which T cells
      can be activated in vitro by endothelial alloantigens. In this report, we focus
      on the first of these pathways: the direct activation of T cells by endothelial
      MHC class I molecules. Using conventional mixed cell cultures and limiting
      dilution analyses, we demonstrate that "resting" allogeneic human umbilical vein
      endothelial cells (HUVEC) stimulate IL-2 production, but not proliferation of
      purified CD3+ PBMC. Transwell experiments demonstrate that soluble suppressive
      factors are not responsible for the lack of proliferation. Instead, they suggest
      that the production of growth factors, such as IL-2, is suboptimal in this
      system. Indeed, submitogenic concentrations of IL-2 synergize with HUVEC to
      induce strong T cell proliferative responses. This proliferation is associated
      with a detectable increase in T cell IL-2R expression, which is not apparent
      after stimulation with HUVEC or IL-2 alone. In conjunction with previous data,
      these observations characterize the first direct pathway of endothelia-induced T
      cell activation. Via this pathway, a small number of CD8+ T cells can be
      activated by the allogeneic MHC class I molecules displayed by resting allogeneic
      endothelial cells. This activation results in the elaboration of IL-2, among
      other things, in concentrations that are too small to promote IL-2R up
      regulation, and thus T cell proliferation. Proliferation readily occurs if
      sufficient IL-2 is available in the environment to overcome this cytokine
      deficit. These studies suggest that endothelial MHC class I alloantigens are
      mildly antigenic to a small subset of T cells. However, in an inflammatory
      environment that is rich in cytokines and growth factors, these endothelial
      alloantigens may become potent direct stimulators of T cell activation and clonal
      expansion.

PMID- 8291097
TI  - Effect of a platelet-activating factor antagonist and desferrioxamine
      administration on eicosanoid production in rat pancreas transplantation.
AB  - Eicosanoid metabolism and its relationship with platelet-activating factor and
      oxygen free radical production in rat pancreas transplantation has been studied
      herein. Male Sprague-Dawley rats were classified in 4 experimental groups (n = 8
      each) as follows: group 1, control; group 2, pancreas transplantation, after 12
      hr of organ preservation in University of Wisconsin solution; group 3, same as
      group 2 with desferrioxamine administration before revascularization of the organ
      in the recipient rat; and group 4, same as group 3 with administration of a
      platelet-activating factor antagonist (BN-52021). The results show post
      transplantation increases in eicosanoid production in pancreatic tissue. The fact
      that desferrioxamine and BN-52021 administration could reverse increases in
      thromboxane B2, leukotriene B4, and 12-hydroxyeicosatetraenoic acid but only BN
      52021 affected 6-keto-PGF1 alpha levels suggests the existence of a close
      relationship between platelet-activating factor and oxygen free radical in
      eicosanoid production in pancreas transplantation and it points to a differential
      role of metabolites produced by circulatory cells and endothelial cells.

PMID- 8291098
TI  - Differential regulation of the macrophage-specific surface antigen RM3/1 by
      cyclosporine, azathioprine, and dexamethasone.
AB  - CsA, AZA, and dexamethasone (DEX) were examined for their ability to modulate
      expression of surface antigens on human monocytes. Peripheral blood monocytes
      were cultured for 1 day, treated with various concentrations of
      immunosuppressants, and subsequently analyzed for expression of macrophage
      differentiation antigen RM3/1, intercellular adhesion molecule-1 (CD54), beta 2
      integrin (CD18), and HLA-DR using flow cytometry and indirect immunofluorescence
      microscopy. The RM3/1 antigen was found to be significantly down-regulated by CsA
      and AZA in a dose-dependent manner, whereas DEX led to a marked up-regulation of
      the RM3/1 molecule. In contrast, expression of CD54, CD18, and HLA-DR by
      macrophages was not affected by treatment with these immunosuppressants. Effects
      of AZA, CsA, and DEX on RM3/1 surface expression were shown to be mediated via
      modulation of RM3/1 de novo synthesis. Immunohistochemical analysis of rejected
      renal allografts revealed that the RM3/1 antigen is expressed by the majority of
      infiltrating macrophages. Our data demonstrate that CsA, AZA, and DEX
      differentially affect gene expression, resulting in distinct macrophage
      phenotypes. Characterization of the RM3/1+ macrophage population in vitro and
      during the course of allograft rejection in vivo may thus provide further
      insights regarding the mode of immunosuppressant action on nonspecific effector
      mechanisms.

PMID- 8291099
TI  - Enzyme release from mitochondria during reoxygenation of rat liver.
AB  - Reoxygenation-induced release of mitochondrial aspartate aminotransferase (mAST)
      into the cytosol was studied using perfused rat liver. As the absolute activity
      of mAST in the perfusate did not indicate the degree of mitochondrial enzyme
      release, the following 3 methods were applied: measurement of the mAST to total
      AST ratio in the efferent perfusate, the digitonin infusion method, and
      measurement of mAST activity in the cytosolic compartment isolated from perfused
      livers. The results by all 3 methods were consistent and showed that
      mitochondrial injury occurs on reoxygenation. The mitochondrial Ca2+ content was
      proportional to the extent of mAST release during reoxygenation, indicating
      involvement of Ca2+ in the enzyme release. CsA, a potent inhibitor of Ca(2+)
      induced increase in permeability of the mitochondrial membrane, completely
      prevented mAST release on reoxygenation. We conclude that during reoxygenation of
      hypoxic liver, mAST leaks into the cytosol in a Ca(2+)-dependent, CsA-sensitive
      manner.

PMID- 8291100
TI  - Temporary withdrawal of immunosuppression for life-threatening infections after
      liver transplantation.

PMID- 8291101
TI  - Can transbronchial biopsy aid in the diagnosis of bronchiolitis obliterans in
      lung transplant recipients?

PMID- 8291102
TI  - Analysis of cytokine production by graft-infiltrating cells isolated from
      rejecting renal allografts.

PMID- 8291103
TI  - Perioperative measures during liver transplantation for erythropoietic
      protoporphyria.

PMID- 8291104
TI  - Endothelin-1 in bronchoalveolar lavage during rejection of allotransplanted
      lungs.

PMID- 8291105
TI  - Successful pancreatic islet autotransplantation to the renal subcapsule in the
      cynomolgus monkey.

PMID- 8291106
TI  - The cost of cytomegalovirus disease in renal transplantation.

PMID- 8291107
TI  - Fulminant hepatic failure.

PMID- 8291108
TI  - Improved survival of in vitro cultured canine islet allografts.
AB  - Pure islets transplanted from single donors survive in outbred dogs when CsA is
      administered at high doses (15-20 mg/kg/day), but not report has documented
      prolonged function with less CsA. In this study, we investigated survival of
      canine islets that were immunomodulated with in vitro culture and transplanted
      with minimal CsA. Highly purified islets from single donors (n = 17) were
      cultured in vitro at 22 degrees C for 7 days. Four groups of apancreatic, outbred
      mongrel dogs received islets into the spleen: group 1 (n = 4), fresh islet
      controls; group 2 (n = 5), cultured islet controls; group 3 (9033 +/- 994
      islets/kg, n = 12), culture and CsA; group 4 (9050 +/- 1091 islets/kg, n = 8),
      fresh islet and CsA. CsA was administered in doses of 5-8 mg/kg/day to maintain
      whole blood trough levels of 300-500 ng/ml. At 30 days after implant, the CsA was
      stopped. After 7-day culture, 80% of the endocrine mass was recovered. All grafts
      restored plasma glucose to < 150 mg/dl. Group 1 and 2 dogs became hyperglycemic
      at 5 +/- 1 (+/- SE) and 6 +/- 1 days. Three grafts in group 3 failed when CsA did
      not reach target blood levels. Of the 9 dogs with CsA levels of 300-500 ng/ml, 1
      died at 9 days while normoglycemic, and the remainder were normoglycemic for 35.5
      +/- 8.3 days (median 38 days). Seven group 4 dogs with these CsA levels achieved
      normoglycemia for 7.7 +/- 1.9 days (median 9 days, survival vs. group 3, P =
      0.03, by Mann-Whitney test). In vitro tissue culture of mass quantities of single
      donor allogeneic islets enhances their survival with low dose immunosuppression
      in outbred diabetic dogs.

PMID- 8291109
TI  - Low temperature collagenase digestion for islet isolation from 48-hour cold
      preserved rat pancreas.
AB  - We examined the efficacy of relatively low temperature collagenase digestion at
      20 degrees C on the yield and viability of islets after long-term cold
      preservation. Wistar rat pancreases were distended with University of Wisconsin
      solution via a pancreatic duct at the time of harvesting to which collagenase and
      2.5 mM calcium chloride were added. The pancreases were cold-preserved at 4
      degrees C for 24 or 48 hr. After storage, they were incubated for collagenase
      digestion at 37 degrees C or 20 degrees C for various incubation periods to
      obtain the peak yield. At 20 degrees C, in vitro collagenase activity measured by
      the FALGPA method was one fourth of that at 37 degrees C, and pancreases were
      well digested with a prolonged digestion period (60-90 min vs. 15-20 min for the
      37 degrees C group). In vitro insulin secretion of islets isolated from freshly
      removed pancreases was maintained at 20 degrees C for 120 min in University of
      Wisconsin solution as compared with 30 min at 37 degrees C. Therefore, the
      preserved pancreases used in this study were incubated either at 37 degrees C or
      20 degrees C at various times in order to obtain peak islet yields. The islet
      yields from 24-hr cold-preserved pancreases at 37 degrees C and 20 degrees C
      digestion were 573 +/- 59/rat (n = 6) and 497 +/- 84/rat (n = 11), respectively,
      and those from 48-hr cold-preserved pancreases were 395 +/- 113/rat (n = 6) and
      414 +/- 75/rat (n = 6), respectively. The yields from 24- and 48-hr cold
      preserved pancreases were significantly low compared with 635 +/- 52/rat for
      fresh pancreases (n = 15), but there was no significant difference between the 2
      methods. The viability of the isolated islets, which was examined by
      transplantation to streptozotocin-induced diabetic C57BL/6 mice, showed a
      significant difference in the capacity to ameliorate diabetes. The functional
      success rate of islet transplantation after 24-hr cold preservation was equally
      good (8/8 for 37 degrees C group vs. 9/10 for 20 degrees C group), but the rate
      for those from 48-hr cold-preserved pancreases was significantly better with
      digestion at 20 degrees C than at 37 degrees C (1/8 for 37 degrees C group vs.
      7/8 for 20 degrees C group, P < 0.05). We concluded that viable islets can be
      isolated from 48-hr cold-preserved pancreases with the low temperature
      collagenase digestion method, which shows promise as a modality for successful
      clinical islet transplantation.

PMID- 8291110
TI  - Functional abnormalities of sinusoidal endothelial cells in rats with acute liver
      rejection.
AB  - The purpose of this study was to determine the changes of hepatic sinusoidal
      endothelial cell (SEC) function in acute liver rejection with respect to receptor
      mediated endocytosis. Orthotopic rat liver transplantation was performed in Lewis
      rats grafted with DA livers and in Lewis rats grafted with Lewis livers as
      rejectors and controls, respectively. Animals were killed at 1, 3, 5, 7, and 10
      days after the operation. Fc receptors (FcRs) were histochemically stained on
      frozen liver sections by applying peroxidase-antiperoxidase IgG complex as a
      ligand, and the FcR activity, i.e., capacity of binding the ligands represented
      by the FcR staining intensity, was semiquantitatively analyzed as an indicator of
      SEC function. The serum level of hyaluronic acid, which is specifically cleared
      from the circulation by receptor-mediated SEC endocytosis, was also assayed,
      along with the total serum bilirubin. Three days after the operation, the SECs of
      rejectors showed a significantly weaker FcR staining intensity of about half the
      value of that seen in the controls (P < 0.05), and staining disappeared after 5
      days (P < 0.01). The decrease of FcR staining intensity, i.e., FcR activity,
      showed a correlation with elevation of the serum hyaluronic acid level (r = 
      0.77; P < 0.001). Histological evidence of endothelialitis and a significant
      elevation of total serum bilirubin (P < 0.01) were also present at 3 and 5 days,
      respectively. These results suggest that impairment of the endocytic function of
      SECs occurs at an earlier phase of acute liver rejection when compared with
      development of abnormalities of traditional indicators. Determination of receptor
      mediated SEC endocytic functions may thus provide useful information for the
      early diagnosis of acute rejection.

PMID- 8291111
TI  - Retroviral-mediated gene transfer into rat experimental liver transplant.
AB  - Replication-defective retroviral vectors were used for ex vivo gene transfer into
      rat liver grafts under conditions mimicking clinical liver transplantation.
      Supernatant containing single- and double-gene vectors encoding for either the
      human IL-7 and/or neomycin phosphotransferase genes were used to perfuse the
      liver grafts during cold ischemia before transplantation. Whole liver grafts were
      perfused with vector supernatant or medium only. Reduced-size liver grafts (50%
      hepatectomy) were similarly perfused either immediately after reduction or 24 hr
      later after induction of active hepatocyte division. After transplantation of
      these grafts in orthotopic position, the liver tissue was removed at specified
      intervals, and genomic DNA and mRNA were examined for proviral sequences and
      expression. Stable integration of the proviral sequences was detected only in
      reduced-size grafts transplanted 24 hr after hepatectomy. Proviral message of
      both neomycin phosphotransferase and human IL-7 were present up to 21 days after
      transduction. This study demonstrates efficient ex vivo gene transfer to donor
      liver grafts. Gene transfer to livers before transplantation carries the
      potential to modulate immunogenicity and alter the antigraft immune response.

PMID- 8291112
TI  - Adenosine deaminase inhibitor in cardioplegia enhanced function preservation of
      the hypothermically stored rat heart.
AB  - Adenosine (ADO) has been shown to be protective to the ischemic-reperfused
      myocardium. This study tested the hypothesis that inhibition of myocardial
      adenosine deaminase during cold storage will elevate tissue ADO content, improve
      the cardiac function, and preserve ATP. The isolated rat hearts (6-9
      hearts/group) were flushed with a cardioplegic solution containing 0-75 microM
      erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and immersion-stored at 0 degree C
      for 9 hr. Function was assessed after 30 min working reperfusion. Function of the
      unstored hearts (n = 11, mean +/- SE) including heart rate (293 +/- 13 bpm),
      aortic flow (AF; 52.5 +/- 1.1 ml/min), coronary flow (CF; 23.5 +/- 1.3 ml/min),
      cardiac output (CO; 76.0 +/- 2.1 ml/min), systolic pressure (SP; 136 +/- 2 mmHg),
      diastolic pressure (DP; 63 +/- 1 mm Hg), work (90.5 +/- 3.4 g-m/min), and
      coronary vascular resistance (CVR; 2.77 +/- 0.14 mmHg-min/ml) served as controls.
      Heart rate in all stored hearts returned to normal after reperfusion. Recovery of
      other function in no-EHNA group was: AF, 52 +/- 7; CF, 55 +/- 5; CO, 53 +/- 6;
      SP, 79 +/- 4; DP, 93 +/- 3; work, 47 +/- 7; and CVR, 171 +/- 15% of control. EHNA
      improved functional recovery in a dose-dependent fashion. At the optimal
      concentration of 25 microM, the recovery was: AF, 83 +/- 6; CF, 68 +/- 4; CO, 78
      +/- 5; SP, 90 +/- 3; DP, 105 +/- 5; work, 77 +/- 8; and CVR 151 +/- 9% of
      control. ADO A1 receptor antagonists, 8-phenyltheophylline (1 microM) and 1,3
      dipropyl-8-cyclopentylxanthine (0.1 microM) blocked the effects of 25 microM
      EHNA; the recovery of CO was reduced to 65 +/- 3 and 50 +/- 2% of the control,
      respectively. Tissue ADO content in 25 microM EHNA hearts at the end of storage
      was 95 +/- 19 nmol/g dry wt, which was significantly elevated from 15 +/- 3
      nmol/g dry wt in no-EHNA hearts. EHNA also caused a 45-fold increase in the
      release of ADO over no-EHNA group during the first 10 min of reperfusion. But
      EHNA treatment did not cause any change in either end-storage or end-reperfusion
      myocardial ATP levels. Thus EHNA in cardioplegic solution inhibited cardiac ADO
      catabolism during long-term hypothermic storage and improved function
      preservation partially via an ADO A1 receptor-mediated mechanism without invoking
      ATP conservation.

PMID- 8291113
TI  - Evaluation of cyclosporine, mycophenolate mofetil, and Brequinar sodium
      combination therapy on hamster-to-rat cardiac xenotransplantation.
AB  - We examined the effect of CsA, mycophenolate mofetil (MM), and Brequinar sodium
      (BQR) combination therapy on hamster-to-rat cardiac xenotransplantation survival.
      Since the mechanism of rejection in concordant cardiac xenotransplantation may be
      antibody mediated as well as cellularly (CD4) mediated, we also examined the
      effect of these agents on antidonor antibody levels. In untreated controls,
      rejection occurred within 4 days, with elevation of cytotoxic antibody titers and
      severe humoral destruction of the xenografted hearts. It involved both IgM and
      IgG antibody-mediated humoral immunity. CsA alone (20 mg/kg/day) could not modify
      this pattern of rejection. High-dose MM (40/20 mg/kg/day)+BQR (12/6 mg/kg 3 times
      a week) combination therapy achieved slight prolongation of survival and
      suppressed the elevation of cytotoxic antibody titers relative to controls. While
      these grafts were rejected within 2 weeks, humoral destruction in the rejected
      xenografts and antibody deposition were reduced. Combination of CsA (20
      mg/kg/day) with BQR (3 or 12 ng 3 times/week) dramatically increased graft
      survival. When CsA (20 mg/kg/day) was combined with MM (20 mg/kg/day) and BQR (3
      mg/kg/day), xenograft survival was significantly prolonged (P < 0.002); however,
      significant toxicity was observed. Cytotoxic antibody formation was delayed for 1
      month in most cases. Histological examination revealed cellular rejection with
      little evidence of humoral rejection. Thus, combination therapy consisting of CsA
      and BQR or CsA, MM, and BQR was effective in delaying the rejection of hamster-to
      LEW rat concordant cardiac xenografts. The mechanism of prolonged graft survival
      may involve delayed humoral response and prevention of the cellular response.

PMID- 8291114
TI  - Renal retransplantation: the role of race, quadruple immunosuppression, and the
      flow cytometry cross-match.
AB  - To assess the impact of quadruple immunosuppression in black and white recipients
      of cadaver kidney retransplants, we reviewed data from 178 second or subsequent
      renal allografts performed at our center between 1985 and 1991. Sixty-six black
      and 102 white recipients were divided into 3 groups: groups 1 and 2 consisted of
      patients with a negative complement-dependent cytotoxicity (CDC) T cell cross
      match, receiving triple drug therapy (CsA-AZA-prednisone) and quadruple
      immunosuppressive therapy (quad therapy; Minnesota antilymphoblast globulin-CsA
      AZA-prednisone), respectively. Group 3 patients also received quad therapy, but,
      in addition to a negative CDC cross-match, had a negative T cell flow cytometry
      cross-match (FCXM). Black and white patients in groups 1 and 2 experienced
      similar graft survival at 1 year, ranging from 47% to 63% (P = NS). In group 3, 1
      year graft survival in whites, but not blacks, improved to 82%, with fewer grafts
      lost to immunologic causes in the first 90 days after transplant. A parametric
      analysis of potential risk factors identified a significant effect of better HLA
      DR matching (P = 0.0005) on improved graft survival, with previous mismatched
      antigens (P = 0.04), female donor (P = 0.002), and short duration of previous
      graft (P = 0.05) as risk factors for graft loss. Race and immunosuppressive
      protocol did not affect graft survival. In group 3, blacks received fewer well
      matched kidneys than whites (P = 0.05), which may have contributed to poorer
      outcomes for black recipients. Nine of 10 patients undergoing retransplantation
      with a negative CDC cross-match and a positive T cell FCXM suffered graft loss at
      a median of 26 days after transplant. Thus, quad therapy did not enhance graft
      survival for either black or white patients undergoing cadaveric
      retransplantation. Immunologic considerations, including HLA-DR matching and the
      FCXM, continue to exert a strong influence on outcomes in these high-risk
      recipients.

PMID- 8291115
TI  - A comparison of rabbit antithymocyte serum and OKT3 as prophylaxis against renal
      allograft rejection.
AB  - A total 166 first cadaveric renal allograft recipients were randomly assigned to
      receive either rabbit antithymocyte serum (RATS) (n = 83) or OKT3 (n = 83) for 10
      to 14 days after transplant as prophylaxis against rejection. Both groups were
      similar with respect to age, sex, donor age, diabetes, time on dialysis, panel
      reactive antibody, HLA matching, and transfusion before transplantation. All
      patients were followed for 1 year after transplantation. A comparison of the
      rejection rates between the 2 groups of patients showed that patients receiving
      OKT3 had a rate of first rejection 1.87 times higher than those receiving RATS
      (95% confidence interval 1.18-2.8, P = 0.007). Twenty-five steroid-resistant
      rejections occurred in OKT3-treated patients as compared with 12 in the RATS
      treated group (P < 0.05). There was no significant difference in early or late
      renal function between the 2 groups of patients. Actuarial 1-year graft survival
      for the RATS group was 78% and for the OKT3 group, 80.7% (P = NS). Actuarial 1
      year patient survival was similar: 89.5% in the RATS group and 94.6% in the OKT3
      group (P = NS). Total hospitalization time was 29.8 +/- 19.9 days for RATS vs.
      39.5 +/- 22.1 days for those treated with OKT3 (P < 0.006). A number of
      infections were observed but there were no significant differences between the
      groups. We conclude that RATS provides better prophylaxis than OKT3 in first
      cadaveric renal transplants because it is associated with fewer rejection
      episodes, less hospitalization, and no additional morbidity or mortality.

PMID- 8291116
TI  - Risk factors predicting chronic rejection of renal allografts.
AB  - Chronic rejection is clinically defined as a gradual but progressive impairment
      of renal allograft function in the absence of other specific causes. The risk
      factors predisposing to chronic rejection are incompletely known. In this
      prospective single-center project, logistic regression analysis was used to study
      the long-term outcome of 94 consecutive first renal allografts in relation to 10
      potential risk factors. Whether serum lipid levels, histopathological changes or
      the mode of immunosuppressive therapy had a predictive value for chronic
      rejection was of special interest. The risk factors for renal allograft outcome
      were determined 2 years after the transplantation, when graft function was still
      normal, and the results were evaluated 2 years later. Occurrence of acute
      rejections, cold ischemia time, the high-density lipoprotein cholesterol level,
      and the high-density lipoprotein and total cholesterol ratio were not significant
      predictors of graft outcome. In a univariate analysis, triglyceride, total
      cholesterol, and low-density lipoprotein cholesterol level, and donor age were
      significantly related to graft outcome. In a logistic regression analysis, triple
      immunosuppressive therapy was better than any double-drug regimen in preventing
      the deterioration of renal allografts. Incipient histological changes in graft
      biopsy, quantitated as the "chronic allograft damage index," was the most
      important single predictor of chronic rejection. The effect of both the
      histological changes and low-density lipoprotein cholesterol on adverse graft
      outcome was level dependent.

PMID- 8291117
TI  - Long-term cardiovascular morbidity and mortality in autosomal dominant polycystic
      kidney disease patients after renal transplantation.
AB  - Patients with autosomal dominant polycystic kidney disease (ADPKD) have an
      increased incidence of hypertension and cardiovascular abnormalities. In this
      long-term follow-up study (5.88 years on average), we evaluated cardiovascular
      disease and patient and graft survival in 101 ADPKD patients and 692 nondiabetic
      control patients receiving cadaveric renal transplants between March 1967 and
      April 1991 at the Leiden University Hospital. Graft and patient survival was not
      different between patient groups, using the same immunosuppressive therapy.
      However, death with functioning graft, mainly due to cardiovascular disease, was
      significantly more frequent in the ADPKD patients than in controls using AZA (P <
      0.01). Multivariate analysis of pretransplant data showed that ADPKD patients on
      AZA therapy demonstrated an elevated age-adjusted relative risk of 2.07 (95%
      confidence interval [95% CI]: 1.12-3.80) for cardiovascular events and 2.88 (95%
      CI: 1.41-5.90) for cardiovascular mortality alone. After adjustment for age,
      gender, and other cardiovascular risk factors, a relative risk of 2.39 (95% CI:
      1.06-5.40) was found. This was 2.87 (95% CI: 1.04-7.93) when cardiovascular
      mortality was the dependent variable. With posttransplant data, the age-adjusted
      relative risk for cardiovascular morbidity and mortality in ADPKD patients using
      AZA was 2.16 (95% CI: 1.12-4.15) and 2.97 (95% CI: 1.40-6.27), with only
      cardiovascular mortality as the dependent variable. After adjustment for age,
      gender, and other cardiovascular risk factors, this was 1.59 (95% CI: 0.64-3.91)
      and 2.28 (95% CI: 0.79-6.53), respectively. With CsA treatment, an elevated risk
      for cardiovascular morbidity and mortality in ADPKD patients was present, but the
      corresponding 95% CI were wide and include unity, due to the shorter period of
      follow-up (CsA: 3.81 +/- 2.50 years vs. AZA: 7.28 +/- 6.74 years). Survival of
      ADPKD patients using AZA was less in those patients without pretransplant
      nephrectomy as compared with control patients, but the morbidity and mortality of
      pretransplant nephrectomies should be taken into account. We conclude that ADPKD
      patients show a similar graft and patient survival after renal transplantation as
      control patients, but they are especially at risk for cardiovascular disease
      after renal transplantation.

PMID- 8291118
TI  - gamma-Hydroxybutyrate mediated protection of liver function after long-term
      hypothermic storage.
AB  - Liver function was measured after 20 hr of hypothermic preservation in University
      of Wisconsin (UW) solution and in modified UW (MUW) solution containing gamma
      hydroxybutyrate (GHB). Rat livers were rapidly cooled by in situ portal flushing
      with chilled UW or MUW solution, then removed and stored at 4 degrees C. After 20
      hr of storage, liver hemodynamics and function were studied during 90 min of
      reperfusion in an isolated perfused liver system. Three groups were investigated:
      livers flushed with and stored in a commercial UW solution for 20 hr (UW group)
      or in a modified UW solution with 500 mg/L of GHB added (MUW group), and livers
      flushed with UW solution and reperfused immediately thereafter (control group).
      Addition of GHB to the cold storage solution significantly improved liver
      function after 20 hr of cold storage. Livers in the MUW group produced bile at a
      much higher rate then those in UW group (3.47 +/- 0.34 vs. 0.87 +/- 0.29 ml/100 g
      liver weight/min at 60 min of reperfusion), while the control livers produced
      4.60 +/- 0.40 ml bile/100 g liver weight/min. At the same time, liver blood flow
      at a perfusion pressure of 11 cm H2O was significantly higher in the MUW group
      than in the UW group (391 +/- 32 ml/min/100 g liver vs. 177 +/- 33 ml/min/100 g
      liver) and only slightly lower than in the control group (494 +/- 49 ml/min/100 g
      liver). Aspartate amino-transferase (AST) and alanine aminotransferase (ALT)
      levels in perfusate samples taken from the venous effluent were raised during
      reperfusion in all groups. However, AST and ALT values were significantly lower
      (503 +/- 88 IU/L/100 g AST, 184 +/- 33 IU/L/100 g ALT) at 90 min of reperfusion
      in the MUW group than in the UW group (1567 +/- 330 IU/L/100 g for AST and 644 +/
      227 IU/L/100 g for ALT). This study clearly demonstrates that GHB greatly
      improves liver function and integrity after hypothermic preservation and has the
      potential to substantially increase the acceptable storage time of donor livers
      before transplantation.

PMID- 8291119
TI  - Selective depletion of CD8+ cells for prevention of graft-versus-host disease
      after bone marrow transplantation. A randomized controlled trial.
AB  - We performed a prospective randomized, double-blind study to assess the efficacy
      of selective depletion of CD8+ bone marrow cells in preventing acute graft-versus
      host disease (GVHD) in 38 patients undergoing HLA-identical sibling donor bone
      marrow transplantation for leukemia. All patients received CsA for GVHD
      prophylaxis. Nineteen patients received marrow depleted of CD8+ cells by ex vivo
      treatment with anti-leu2, an anti-CD8 mAb and complement; four patients had
      moderate (grade 1 or 2 acute GVHD) and the only patient who experienced grade 3
      manifestations was a technical failure. The control group consisted of 19
      patients who received unmodified bone marrow; one patient had grade 1, 4 patients
      had grade 2, and 10 had grade 3 or 4 acute GVHD. The actuarial incidence of grade
      > or = 2 acute GVHD was 20 +/- 20% in the CD8-depleted group compared with 80 +/-
      18% in the controls (P = 0.004). Death in 5 of the control patients and the
      single patient in whom CD8 depletion was a technical failure was related to acute
      GVHD. Graft failure occurred in 2 patients in the CD8-depleted group and in none
      of the controls. Leukemic relapse occurred in 2 patients receiving CD8-depleted
      bone marrow and 2 patients in the control group. Seven patients receiving marrow
      depleted of CD8+ cells are alive and free of leukemia and 9 patients in the
      control group are alive, 7 of whom remain leukemia-free (P = 0.88). The 3-year
      actuarial leukemia-free survival is 37 +/- 22% of the CD8-depleted group and 36
      +/- 22% for the control group. These results indicate that selective depletion of
      CD8+ cells from the bone marrow significantly reduces the incidence and severity
      of acute GVHD.

PMID- 8291120
TI  - Pulmonary hemorrhage as a cause of death in allogeneic bone marrow recipients
      with severe acute graft-versus-host disease.
AB  - Acute graft-versus-host disease (GVHD) has recently been associated with
      endothelial cell injury. The potential clinical significance was explored here in
      an autopsy review. Thirty-seven allogeneic bone marrow recipients were identified
      in the autopsy files at The Johns Hopkins Hospital with no evidence of systemic
      infection. Forty-one percent (15/37) of these patients were found to have
      extensive recent pulmonary hemorrhage at autopsy which was thought to have led to
      terminal respiratory failure and death. The 37 patients were divided into 2
      groups: those with significant acute GVHD (stage 2 or greater) and those without
      GVHD (stage 0 or 1). Fifty-nine percent (10/17) of the patients with significant
      acute GVHD died of acute respiratory failure due to recent pulmonary hemorrhage
      as opposed to 25% (5/20) of those without acute GVHD (P = 0.032, Fisher's exact
      test). Terminal pulmonary hemorrhage was also associated with preparation for
      BMT, with 67% (12/18) of those prepared with total body irradiation (TBI) having
      pulmonary hemorrhage as opposed to 15% (3/19) of those prepared with chemotherapy
      using Busulphan (P = 0.002). There was no significant difference in
      posttransplant survival, engraftment, or final platelet count between the
      patients stratified by GVHD or preparative protocol. The data support a strong
      association between significant acute GVHD and terminal hemorrhage, as well a
      possible association between TBI and pulmonary hemorrhage. Analysis of variance
      demonstrates that GVHD and TBI are independently associated with increased
      pulmonary hemorrhage (P < 0.01 for GVHD, P < 0.001 for TBI). We propose that GVHD
      contributes to terminal pulmonary hemorrhage by injuring the endothelium.
      However, this association could also be a secondary effect, i.e., toxicity from
      therapy for GVHD, or an abnormality in cytokines or growth factors. The
      pathogenic relationship between significant GVHD and terminal hemorrhage is
      discussed briefly.

PMID- 8291121
TI  - Endoscopic variceal ligation.

PMID- 8291122
TI  - Preoperative biliary decompression-ritual or a must?

PMID- 8291123
TI  - The use of flumazenil in reversing the midazolam and diazepam sedation in
      outpatients undergoing gastroscopy.
AB  - A prospective double blind randomized study was conducted to assess the efficacy
      and safety of flumazenil in patients for upper gastrointestinal endoscopy,
      sedated with midazolam or diazepam. Flumazenil significantly reduced the degree
      of sedation in both treatment groups without significant intergroup differences.
      There was no evidence of rebound sedation during the observation period of 4
      hours. Anterograde amnesia was effectively antagonized in both groups. Flumazenil
      was a well tolerated safe and effective benzodiazepine antagonist. The
      combination of benzodiazepine with flumazenil makes it possible to reduce the
      recovery period and may be useful in outpatients undergoing endoscopy.

PMID- 8291124
TI  - Bacterial and cryptosporidial infection as the cause of chronic diarrhoea in
      patients with liver disease in Nepal.
AB  - Chronic diarrhoea is common in patients with liver disease in Nepal. It is often
      seen in patients with alcoholic liver disease (ALD) and those with obstructive
      lesions of the hepatic portion of the inferior vena cava. To assess the role of
      bacterial and parasitic infection in patients with chronic diarrhoea, microscopic
      examination and culture of the stool were done in 30 cases. Pathogenic bacteria
      were isolated in 23 (76%), Yersinia sp was isolated in 9 (26%), Klebsiella and
      Shigella sp. in 3 each and Listeria sp in 1 patient. Oocysts of Cryptosporidium
      was demonstrated in the stools of 6 (20%) patients.

PMID- 8291125
TI  - Treatment of patients with chronic hepatitis using ursodeoxycholic acid.
AB  - We treated 82 patients of chronic hepatitis using 300 mg. of ursodeoxycholic acid
      (UDCA) daily and observed them for a mean of 10 mo before and 16 mo after UDCA
      administration. Seven liver function tests (AST, ALT, ALP, LAP, GTP, Ch-E and T
      cholest) were assessed monthly. The values were compared before and after the
      administration of UDCA. The AST, ALT, LAP and GTP improved significantly in the
      UDCA treated patients, whereas ALP, Ch-E and T-cholest. did not show any change
      throughout the study. Amongst the liver function tests that improved, the serum-
      GTP level, in particular decreased markedly and rapidly in patients treated with
      UDCA. Although UDCA 600-mg daily was administered in patients who showed lack of
      improvement with 300-mg UDCA treatment, no significant improvement was obtained.
      Repeated liver biopsies were carried out in six of the 42 patients in whom liver
      biopsy had been performed before the administration of UDCA. We detected no
      histological changes during the UDCA treatment. There were no side effects
      related to therapy with UDCA. In conclusion, we confirmed that UDCA is a safe and
      effective drug for treating patients with chronic hepatitis and may help in
      prevention of progression of the disease, particularly in patients with a high
      serum--GTP level.

PMID- 8291126
TI  - Young age carcinoma stomach with spontaneous bacterial peritonitis.
AB  - A case of disseminated carcinoma stomach at the age of thirteen years is
      reported. The patient in addition had spontaneous bacterial peritonitis.

PMID- 8291127
TI  - Solitary non-parasitic cysts of the liver: presentation and management.
AB  - Four cases (one asymptomatic and three symptomatic) of solitary non-parasitic
      cysts of the liver are presented. The asymptomatic cysts was an incidental
      finding at laparotomy. The other three patients presented with abdominal
      distension, jaundice and malignant transformation respectively. Management of
      these patients has been discussed and the literature reviewed.

PMID- 8291128
TI  - Prognostic evaluation of perineural invasion in rectal cancer.

PMID- 8291129
TI  - [Isolation of cellular retinol-binding protein from cattle liver].
AB  - Cellular retinol-binding protein from bovine liver has been purified to
      homogeneity. The protein binds retinol with high affinity; the apparent
      dissociation constant was determined by fluorometric titration to be 2.18 x 10(
      3) M. Retinol bound to the protein has an absorption spectrum (lambda max = 350
      nm) and considerably differs from the spectrum of retinol absorption in ethanol
      (lambda max = 325 nm). The protein is a single polypeptide chain with a molecular
      weight of approximately 14 kDa based on information obtained by sodium dodecyl
      sulfate-polyacrylamide electrophoresis.

PMID- 8291130
TI  - [Effect of the complexes tocopherol-protein-acceptors and tocopherylquinone
      protein-acceptors on the activity cytosol phospholipase A2 in rat liver].
AB  - A new method of tocopherol and tocopherylquinone binding with rat liver cytosol
      proteins-acceptors. Complexes tocopherol-proteins-acceptors and tocopheryl
      quinone-proteins acceptors have been studied for their effect on phospholipase A2
      activity. It is established that the both complexes are the inhibitors of
      phospholipase A2, under these conditions tocopherylquinone complex with proteins
      acceptors more intensively decreases Km of the enzyme than the complex tocopherol
      proteins-acceptors.

PMID- 8291131
TI  - [Reduction of cytochrome p-450 content and activity by porphyrins after damage to
      the microsomal membrane by tetrachloromethane].
AB  - Natural porphyrin (hemin and its synthetic analogue--tetraphenylporphyrin with
      iron TPP-Fe3+) has been studied for its effect on activity of monooxygenase
      responses and cytochrome P-450 content against a background of introduction of
      four-chlorine carbon in the in vitro experiments. The reducing effect of hemin
      and TPP-Fe3+ on cytochrome P-450 and dependent enzymes: N-demethylase, n
      hydroxylase and benz(a)pyrene hydroxylase has been noticed; the synthetic
      analogue of heme was more efficient.

PMID- 8291132
TI  - [Activity of antioxidant defense enzymes and the state of lipid peroxidation in
      the rat brain in decis and dichlofos poisoning].
AB  - The activity of the antioxidant system enzymes--superoxide dismutase (SOD) and
      catalase and lipids peroxidation in the rat brain under deltametrin and
      dichlorvos intoxication has been studied in vivo. It was shown that both
      xenobiotics lowered SOD activity 30 minutes after the injection. Accumulation of
      superoxide ions as a result of inhibition of SOD activity may stimulate lipid
      peroxidation of biological membranes. Activation of lipid peroxidation in the rat
      brain in vivo under dichlorvos and deltametrin intoxication was established. It
      was shown in the in vitro experiments that deltametrin (but not dichlorvos)
      stimulated NADPH-induced lipid peroxidation.

PMID- 8291133
TI  - [Antioxidant activity of a new derivative of 4-hydrazinoquinazoline in
      experimental cerebral hypoxia].
AB  - It is established that KS-79 compound possesses the high level of antioxidant
      activity and realizes its antioxidant effect at initial stages of free-radical
      hydrogen peroxide oxidation of lipids. Due to this ability it differs from the
      oxidants of direct-type action.

PMID- 8291134
TI  - [Structure and organization of class I interferon molecules].
AB  - The regular structure of class I interferon molecules was proposed using the new
      method of protein structure investigation--the comparative analysis of amino
      acids codon roots. It was found out that IFN-alpha and IFN-omega molecules are
      formed of 5 repeats. Each repeat can be divided into two parts or blocks with
      regular (alpha-spiral, block A) and irregular (parts of molecules between alpha
      spirals, block B) structures. Localization of blocks A and B in IFN-alpha
      molecules has good correlation with the models of secondary structure
      organization of IFN-alpha. It is supposed that such a structure of IFN molecules
      is formed in the evolution process as a result of multiplication of IFN primary
      gene.

PMID- 8291135
TI  - [Determination of the optimal condition of hemoprotein immobilization on the
      polystyrene surface].
AB  - The effect of pH, buffer composition, salts concentration and protein content on
      the immobilization efficiency of peroxidase, hemoglobin and their conjugates with
      bovine serum albumin (BSA) have been studied. All the substances were immobilized
      on the surface of polystyrene matrix. When using the 0.01 M carbonate-bicarbonate
      buffer (pH 9.6) immobilization of soluble substances is optimal. It was shown
      that the sorption efficiency of hemoproteins and their conjugates with BSA is
      considerably enhanced by drying solution containing ammonium bicarbonate. The
      increase of ammonium bicarbonate concentration from 0.13 M to 0.5 M leads to the
      process intensification.

PMID- 8291136
TI  - [Role of complex formation between cytochrome c and NADH in the display of
      dinucleotide photosensitizing effect with respect to hemeprotein].
AB  - UV-irradiation of free ferricytochrome c solutions in a dose 27.18 x 10(2) J/m2
      (37 degrees C) induced the photoreduction of the enzyme molecules at pH 6.0 and
      8.0. The process of hemoprotein photoreduction intensified after irradiation of
      the ferricytochrome c--NADH mixture at pH 6.0: dinucleotide photo-sensibilizing
      effect in respect to ferricytochrome was observed. This effect of NADH was not
      revealed in case of irradiation of the ferricytochrome c--NADH system at pH 8.0
      and 4.0. Each component of the investigated system eluted from gel-chromatography
      column separately (two fractions were revealed) at pH 8.0. The above system is
      divided into four fractions at pH 4.0: the 1st fraction corresponds to free
      ferricytochrome c solution but 2.4 fractions--to the NADH molecular degradation
      products. Ferricytochrome c and NADH are eluted from gel-filtration column as a
      single fraction at pH 6.0. It means that the coenzyme photo-sensibilizing effect
      displays in case of its complex formation with hemoprotein.

PMID- 8291137
TI  - [Carbohydrate-binding proteins--lectins and glycosidases in plants of Anthurium
      genus].
AB  - The content of lectins and activity of glycosidases have been estimated in seeds
      and vegetative organs of 5 strains of plants of Anthurium genus. In seeds of all
      the investigated strains lectins were detected with the selectivity toward the N
      acetyl-galactosamine (minimal inhibitory concentration of sugar was 0.1-0.2 mM)
      and an anti-A blood group specificity. Lectins of Anthuriums selectively bound O
      type glycosidic chains and revealed high affinity toward mucins (salivary or
      ovary cysts origin). Lectins were not detected in vegetative parts of Anthuriums.
      In seeds of plants the following glycosidases were detected in the diminishing
      activity order: alpha-galactosidase, alpha-mannosidase, beta-galactosidase, beta
      glucosaminidase.

PMID- 8291138
TI  - [Metabolism of lactic acid stereoisomers in living organisms].
AB  - The present state of one of the sections of dynamic biochemistry concerning
      lactic acid enantiomers metabolism has been examined. Data on the distribution
      and activity of L- and D-lactate NAD+ oxidoreductases in various biological
      objects have been summed up. Probable involvement of prochiral and chiral
      compounds that stimulated biogenesis in the processes of quasi-metabolism self
      organization and chiral purity of biosphere has been supposed.

PMID- 8291139
TI  - [Effect of alpha-halogen-alpha-nitroalkanes on methemoglobin formation and
      activity of antioxidant enzymes in mouse erythrocytes].
AB  - It is shown that 1-chlorine, 1-bromine and 1-iodine-nitroethanes intensify
      methemoglobin formation in vivo. Such an effect was not revealed for 1-fluorine-1
      nitroethane. Change of biochemical parameters of erythrocytes under intoxication
      by alpha-halogen nitroalkanes in a dose LD50 with the exception for 1-fluorine-1
      nitroethane is rather identical with that under the intoxication by soda nitrite
      which is connected with the generality of reaction mechanism of soda nitrite and
      alpha-halogen-alpha-nitroalkanes with hemoglobin. Thus the administration of
      alpha-halogen-alpha-nitroalkanes to laboratory animals leads to the increase of
      the total activity of dehydrogenases of pentose phosphate way and glutathione
      reductase of erythrocytes (on the example of 1-iodine-1-nitroethane), the
      increase of lipoperoxidation (on the example of 1-bromine-1-nitroethane), the
      decrease of catalase activity. Absence of the inhibition of superoxide dismutase
      activity was found under the intoxication by all the mentioned drugs. The
      increase of activity of glutathione reductase of erythrocytes (on the example of
      (1-iodine-1-nitroethane) under intoxication with alpha-halogen-alpha-alkanes in
      contrast to intoxication by soda nitrite is explained by some differences of
      mechanisms of hemoglobin interaction with soda nitrite and alpha-halogen-alpha
      nitroalkanes.

PMID- 8291140
TI  - [Interaction of spin labels and probes with Na+,K+-ATPase].
AB  - Localization of the PCMB-R spin label and benzocarboline probe bound with the
      purified preparation of pig kidney-Na+, K(+)-ATPase relative to active site of
      the enzyme was studied by EPR method. The number of Mn2+ ions in active site of
      the enzyme as well as that bound with lipids was determined from EPR spectra of
      paramagnetic manganese ions replacing magnesium ions were measured in frozen
      protein samples of Na2+, K(+)-ATPase at 77 K. It has been found that sulfhydryl
      group of the enzyme modified by PCMB-R and benzocarboline probe are placed at
      distances 38 A and 50 A, respectively, from Mn2+ ions in the active site of Na+,
      K(+)-ATPase. Evaluation of the immersion depth of the nitroxyl radical into
      protein globule showed that benzocarboline probe was immobilized near the
      macromolecular protein surface; there are two bound probe sites, distinguished by
      accessibility of ferricyanide ions.

PMID- 8291141
TI  - [Leukocyte mobility in modulation of activity of the cell signalling system].
AB  - The mobility of the rat polymorphonuclear leukocytes (PMNL) has been studied. It
      was shown, that it is greatly determined by the balance of adenylate cyclase
      (AdC) and Ca-polyphosphoinositide (Ca-PPI) cell signalling systems. Various
      compounds whose action on the activity of the signalling systems was previously
      connected with the membrane receptors, proved to be capable to affect the
      activity of submembrane elements of these systems. It is concluded that multiple
      areas of bioregulators fixation within the limits of the signal cascades are
      available.

PMID- 8291142
TI  - [Characterization of enzymatic activity and structure of vesicles of human
      erythrocyte membranes].
AB  - Enzymatic activity and structural peculiarities of human erythrocyte membranes
      obtained by different methods, are analyzed in the paper. Our studies have
      demonstrated different enzymatic activity of the preparations of right side- and
      inside-out vesicles of human erythrocyte membranes. Fluorescence probes of pyrene
      and ANS have shown that these membrane preparations have different physical
      characteristics of lipid and conformational properties of membrane proteins and
      differ in the composition of their protein-lipid ensembles.

PMID- 8291143
TI  - [Uterotonic action of sigetin and its effect on the Mg2+, ATP-dependent transport
      and stationary metabolism of Ca2+ through the myometrial sarcolemma].
AB  - The effect of sigetin (dipotassium salt, meso-3, 4-di-(n-sulfophenyl)- hexane) on
      the electrical and mechanical activity, Ca2+, Mg2+-ATPase activity and Mg2+, ATP
      dependent Ca2+ transport in uterine smooth muscle have been investigated. Sigetin
      caused depolarization of the cell membrane, leading to Ca2+ dependent spike
      discharge and development of mechanical response. Sigetin also produced
      deceleration of the relaxation of carbachol contracture controlled mostly by the
      sarcolemmal ATP driven Ca2+ pump. The drug produced strong inhibition of Mg2+,
      ATP-dependent Ca2+ transport in sarcolemmal vesicles as well as the enzyme and
      transport activity of the solubilized Ca2+, Mg(2+)-ATPase reconstructed in
      liposomes. Under the experimental conditions close to the physiological (i.e. in
      the presence of an outwardly directed Ca2+ gradient) Ca2+ pump normally
      compensates passive release of this cation. Sigetin was found to shift this
      calcium equilibrium towards a non-compensated slow diffusion of the cation in the
      extravesicular space. Addition of sigetin to the incubation medium during the
      existence of the stationary transmembrane Ca2+ equilibrium stimulates transition
      of the stationary concentration of the cation in vesicles from high to lower
      level. The results suggest that the excitatory action of sigetin on myometrial
      smooth muscle may involve not only indirect stimulation of Ca2+ influx via the
      voltage operated Ca2+ channels but also through the inhibition of the ATP driven
      Ca2+ pump of the cell membrane.

PMID- 8291144
TI  - [Comparative study of the effect of cycloartane and cardiac glycosides on various
      parameters of myocardial metabolism in animals].
AB  - Administration of cycloartane (askendoside D-10 mg/kg, cyclosiversioside F-25
      mg/kg) and heart glycosides (strophanthin K-0.36 mg/kg, celanide-1 mg/kg) for 3
      10 days is found to exert unidirectional effect on the indices of carbon, lipid
      and adenine nucleotide metabolism in animal myocardium under study. Glycogen and
      ATP content increases under parallel decrease of lactate and nonesterified fatty
      acid content. Differences in the effect of cycloorthane and heart glycosides and
      especially on the indices of myocardial carbon metabolism were registered under
      more prolonged administration. Administration of heart glycosides in contrast to
      cycloorthane ones promotes a decrease of glycogen level and redox potential and
      increase of lactate content.

PMID- 8291145
TI  - [Correlation of acid-base equilibrium and glycolysis during muscle activity].
AB  - Interdependence between acid-base equilibrium of blood and accumulation of
      lactate depending on the intensity of exertion during swimming and individual
      reaction to the exertion has been analyzed when examining high-qualification
      sportsmen. Prognostication and optimization criteria of acidosis prophylaxis are
      suggested.

PMID- 8291146
TI  - [Energy metabolism in newborn calves].
AB  - It has been studied that peculiarities of redox processes of glycolysis and of
      citrate cycle in newborn calves under oxygen shortage has been caused by diarrhea
      under acute disturbances of digestion. It was shown that concentration of oxalo
      acetate, L-ketoglutarate, glutamate increases and concentration of malate
      lactate, pyruvate decreases when partial pressure of oxygen rises in the venous
      blood of calves. Change of activity succinate dehydrogenase depends on the degree
      of pathological process.

PMID- 8291147
TI  - [Metabolism of vitamin B1 and its di- and triphosphate esters in experimental
      allergic encephalomyelitis].
AB  - Biological significance of thiamin in development of experimental allergic
      encephalomyelitis has been elucidated. It has been shown that at the late
      preclinical stage of the disease thiamine metabolism is predominantly directed
      towards the maintaining of cellular metabolic homeostasis, whereas at the stage
      of clinical symptoms the anabolic process gives way to catabolic decomposition.
      Among tested thiamine phosphates the triphosphate ester is the most informative
      parameter in demyelinizing processes. Thiamine injections to immunized animals
      accelerate the vitamin phosphorylation depleting the reducing and energy
      potentials of the cell. Such thiamine antagonist as oxythiamine inhibits
      phosphatase reactions.

PMID- 8291148
TI  - [Effect of tocopherol, its analogs and the antioxidant ionol on lipid
      peroxidation in vitro].
AB  - Ionol, alpha-tocopherol and its analogues (tocoferenquinones with C6 and C1 in
      the side chain, tocopherol without the side chain and two tocopherols with
      shortened to C6 side chain both with saturated and with unsaturated bond at the
      end) were studied for their effect on the formation rate of malonaldehyde in the
      tissue and liver mitochondria of vitamin E-deficient rats in vitro. Preparations
      were used in two concentrations: 35 mg per 1 ml of the medium--in a dose
      suppressing processes or lipid peroxidation; and 5 mg per 1 ml of the medium--in
      a dose activating biosynthesis of ubiquinone in the animal tissues. Tocopherol
      effect on lipid peroxidation processes in the liver tissue and mitochondria is
      shown to be different and to depend on its concentration in the medium. Ionol is
      efficient only in high doses under the conditions in vitro. Tocopherol analogues
      (their side chain being shortened to six carbon atoms) display maximum activity
      when they inhibit lipid peroxidation both in the liver tissue and mitochondria in
      the both concentrations under study which supposes their high efficiency under
      the conditions in vivo.

PMID- 8291149
TI  - [Medical quality assurance--implementation of research results].

PMID- 8291150
TI  - [Meta-analysis: new demands put on the clinician. Denmark has a central position
      in the international Cochrane-cooperation].

PMID- 8291151
TI  - [Reproducibility of electrocardiographic interpretation in patients with
      suspected myocardial infarction. A controlled study of the effect of a training
      trial].
AB  - We examined the effect of a training programme to reduce interobserver variation
      in interpretation of electrocardiography in suspected myocardial infarction.
      Sixteen doctors with 6-24 months of clinical training in internal medicine read
      serial electrocardiographic recordings in 107 patients and assessed whether signs
      indicative of acute myocardial infarction were present. There was disagreement in
      approximately 70% of cases. Eight of the doctors were randomly allocated to
      attend an eight hour long intensive course on interpretation of
      electrocardiography in myocardial infarction. The remaining eight participants
      were allocated to a control group, received no training, and were not told about
      the subject of the study. All the doctors then reviewed another series of
      electrocardiographic recordings. No difference was found in the level of
      agreement within the two groups before and after the training programme, or
      between the two groups before and after the training. The raters' ability to
      discriminate between electrocardiograms with a high and low indication of
      infarction remained unaffected. We conclude that the training programme did not
      increase agreement regarding the interpretation of electrocardiographic data in
      suspected myocardial infarction. Our results suggest that the diagnostic approach
      of physicians is established at a very early stage in their clinical training.
      The effect of training programmes should be evaluated by the use of randomized
      clinical studies.

PMID- 8291152
TI  - [Bronchodilating inhalation anesthetics in bronchial asthma and status
      asthmaticus].
AB  - On the basis of a review of the literature, a survey is presented concerning the
      use of halogenated inhalational anaesthetics (halothane, enflurane, isoflurane)
      in anaesthesia of asthmatic patients and in intensive care units in the treatment
      of status asthmaticus refractory to maximal standard therapy. Particular emphasis
      is placed on the bronchospasmolytic, cardiovascular and organotoxic effect of the
      anaesthetics. It is concluded that halogenated inhalational anaesthetics are
      established as bronchospasmolytics, and that their use in bronchospastic disease
      should be individualized to the patient and his other specific disease process.

PMID- 8291153
TI  - [Cardiac risk in surgery. A review and guidelines for risk evaluation and
      reduction of cardiac risk in general surgery].
AB  - Cardiac complications occur with an incidence of 2-6% and are a main cause (15
      20%) of mortality after non-cardiac surgery. Cardiac risk should be determined
      and reduced by treatment preoperatively and by an intraoperative and
      postoperative care that has been adjusted to the increased risk. This review
      provides recommendations concerning risk evaluation and management.

PMID- 8291154
TI  - [Pacemaker treatment in Greenland].
AB  - In a retrospective survey, treatment with pacemakers in Greenland during the 29
      year period of August 1962-August 1991 is described, and the 179 Greenlandic
      patients treated are investigated. The annual rate of first-time pacemaker
      implantation is today 200 per million in Greenland, compared to 238 per million
      in Denmark; the population in Greenland is young, and according to the age
      distribution 75% more patients are operated in Greenland. Two-thirds are men and
      one-third women, mean age of 68 years (range 41-85 years). The Greenlandic
      patients are younger than patients in Denmark. About two-thirds are treated for
      atrioventricular block and one-third for sick sinus syndrome. Seventy-four
      patients were implanted with epicardial leads, which functioned for an average of
      3.4 years. The mean time for the period of pacemaker treatment was five years.
      Eighty-four percent of the patients operated between May 1983 and August 1991,
      are still alive. In the same period, the rate of operative complications was 12%,
      and two patients died because of infection.

PMID- 8291155
TI  - [The significance of prognostic factors on the occurrence of metastases from
      breast cancer to various localizations].
AB  - The aim of the study was to identify and compare risk factors for development of
      metastases from breast cancer at specific anatomical sites. The sites were
      grouped into ten categories, simultaneous occurrences at several sites being
      common. The influence of various risk factors for recurrence at one specific site
      can be modelled by well-established survival analysis techniques such as the Cox
      regression model. Recently, a generalization has been proposed that allows for
      joint occurrences at more than one site. The prognostic influences of various
      risk factors on recurrence at different sites may be compared using these models.
      Both methods were applied to data from the Danish Breast Cancer Cooperative Group
      on recurrence after breast cancer; the risk factors examined were degree of
      anaplasia, number of positive lymph nodes, site of primary tumour, skin or deep
      fascial invasion, age of the patient and adjuvant treatment regimens. Adjuvant
      therapy had the same effect on recurrence at all sites. For chemotherapy, this
      effect was marginally significantly positive. The number of positive lymph nodes
      was associated with an increased risk of metastases at all sites except the
      brain, where an opposing trend was found. The degree of anaplasia was associated
      with a somewhat increased risk of metastases at all sites, again the brain was an
      exception, here the effect of degree of anaplasia was significantly more
      pronounced. Application of the new types of models resulted in fewer differences
      between the relative influence of the prognostic factors than are implied by the
      use of the traditional regression models.

PMID- 8291156
TI  - [Partial versus total meniscectomy. A prospective, randomized study].
AB  - Two hundred patients with a meniscus lesion were peroperatively allocated to
      partial or total meniscectomy. The results were compared at one year and at 6.3
      9.8 years (median 7.8). After one year, more patients with partial meniscectomy
      (90%) than with total meniscectomy (80%) had no complaints (p = 0.029). At the
      late review these figures were 62% and 52% respectively (p = 0.18). However,
      patients with partial meniscectomy had the highest functional scores. In five
      percent knee joint function had improved and in 35% deteriorated, in the latter
      group without detectable difference between partial and total meniscectomy. The
      incidence of lateral laxity rose from eight to 47%, most frequently seen after
      total meniscectomy. During the observation period radiological signs of knee
      joint degeneration changed from solely joint line narrowing into additional ridge
      formation and flattening of the femoral condyle, but unrelated to whether partial
      or total meniscectomy had been performed. Following partial meniscectomy
      posterior horn lesions had the poorest functional outcome, but only if more than
      one third of the meniscal surface had been removed. The amount of meniscal tissue
      excised was inversely correlated to the level of knee joint function except in
      bucket handle lesions treated with partial meniscectomy. These lesions had the
      largest areas of meniscal tissue removed, but higher functional scores than
      posterior horn lesions. Preservation of the peripheral rim of the meniscus
      following partial meniscectomy was essential for the functional outcome after
      surgery.

PMID- 8291157
TI  - [Laparoscopic vaginal hysterectomy].
AB  - Laparoscopic assisted vaginal hysterectomy (LAVH) is a rather new operative
      procedure in Denmark. During the period 1.12.1992-28.02.1993 we performed ten
      LAVH. The procedure is described. The operations were performed with bipolar
      coagulation and subsequent cutting with scissors. The average operating time was
      two hours. The average uterine weight was 130 g and total average hospital stay
      was two 2.8 days. In one patient laparotomy had to be performed due to arterial
      bleeding close to the right ureter. One patient developed a postoperative
      haematoma with temporary stasis of the right ureter. Both patients recovered.
      Adequate laparoscopic training in humans and animals is mandatory before LAVH is
      performed. In the learning phase it is advisable that the uterine size does not
      exceed 200 g.

PMID- 8291158
TI  - [Validity of postmortem alcohol determination].
AB  - The aim of this study was to establish the confidence interval for the
      determination of alcohol in post-mortem material. The calculations in the study
      concern cases in which two blood samples had been taken from a dead body with the
      purpose of determining alcohol content of the blood. The confidence interval
      (calculated as twice the standard deviation) was found to be 0.50 per thousand.
      The study confirms the previously established slight decrease in the
      concentration of alcohol in the blood during the first hours after death. No post
      mortem alcohol production was found to have taken place during the first 24 hours
      (approx.) if the body had been kept at a low temperature. It is concluded that a
      confidence interval of 0.50 per thousand should be applied in the evaluation of
      post-mortem alcohol determination. In cases of visible putrefaction of a corpse
      an individual assessment must be made.

PMID- 8291159
TI  - [Severe bronchospasm in a 1-year old child treated with halothane].
AB  - A case of severe bronchospasm in a one-year old mechanically ventilated girl
      which in spite of maximal conventional bronchodilatory treatment only responded
      to halothane inhalation is presented. The benefits and limitations of this
      therapy are discussed.

PMID- 8291160
TI  - [Antral vascular ectasia--"water-melon stomach". An overlooked cause of iron
      deficiency anemia?].
AB  - Antral vascular ectasia or "the watermelon stomach" (WS) is an endoscopically,
      histologically and clinically distinct entity. The term WS reflects the
      endoscopic appearance of longitudinal antral erythematous folds containing
      visible vessels radiating from the pylorus. Histological examination demonstrates
      characteristic features including dilated mucosal capillaries, focal thrombosis
      and fibromuscular hypertrophy of the lamina propria. The clinical picture is
      characterized by severe chronic iron deficiency anaemia, and failure to recognize
      WS has frequently delayed adequate treatment for several years. Antrectomy is a
      definitive cure. Both endoscopic laser- and sclerotherapy seem to be promising
      alternative methods in the treatment of WS.

PMID- 8291161
TI  - [Occupational bladder cancer].

PMID- 8291162
TI  - [Increased mortality in relation to weight loss--a dietary cure as a possible
      cause].

PMID- 8291163
TI  - [Significance of breast feeding in certain virus infections].

PMID- 8291164
TI  - [Working conditions of general practitioners].

PMID- 8291165
TI  - Low-dose thickness measurement of glucose-embedded protein crystals by electron
      energy loss spectroscopy and STEM dark-field imaging.
AB  - Electron energy loss spectroscopy and dark-field imaging in a scanning
      transmission electron microscope were used to determine the thickness of glucose
      embedded crotoxin complex crystals. The results demonstrate the feasibility of
      identifying protein crystals with a thickness of half a unit cell (12.8 nm) under
      low-dose and low-temperature conditions. The accuracy of this method is limited
      by the amount of surface coating of the crystal's embedding glucose used for
      preserving the high-resolution structure of the protein. The histogram of the
      crystal thickness distribution and the spread of the anticipated crystal
      thickness allow us to make an estimate of the uncertainty in the glucose layer
      thickness. This approach can be incorporated as part of the experimental
      procedure in the three-dimensional data collection for structure determination of
      protein crystals with variable thicknesses. The measurement can be done on areas
      approximately 200 nm in diameter so that crystals of suitable thickness can be
      pre-selected before the high-resolution data is recorded. Accurate determination
      of the crystal thickness will optimize the data collection efficiency by avoiding
      the collection and subsequent analysis of unmatchable data for the three
      dimensional reconstruction.

PMID- 8291166
TI  - [Quality of life connected with nursing practice and research--some challenges].
AB  - Quality of life is increasingly being recognized as an important outcome in
      patient care. In spite of the popularity of the concept, its use is not without
      difficulties. Because quality of life is a subjective phenomenon it is not easy
      to define, as no gold standard exists as to what is a good life. This has
      resulted in different definitions of quality of life as well as discrepancies of
      design and development of instruments to measure the construct within different
      sciences. The usefulness of quality of life within nursing research and practice
      is dependent on: 1) the way the concept is defined and operationalized, 2) the
      clinical relevance of the questions raised in the study, 3) study design and 4)
      further methodological development.

PMID- 8291167
TI  - [Quality assurance by developing strategical and professional nursing care
      goals].
AB  - Quality assurance by developing strategical and professional nursing care goals.
      The purpose of this study was to develop strategical and professional nursing
      care goals. The theoretical base for the study was the 'VIPS-model' This model
      includes four concepts: well-being, integrity, prevention and safety, from which
      a taxonomy is generated. In order to measure the quality of nursing care the
      DySSSy-model was used. Four standards, based on the previously mentioned concepts
      were developed and evaluated at two surgical wards. The ward nurses were asked
      through a questionnaire how they valued the strategical and professional nursing
      care goals. The conclusion from the study is (1) that the taxonomy can be useful
      for structuring strategical and professional nursing care goals (2) that three of
      the developed standards are useful at surgical wards, and (3) that the
      questionnaire can be used as an instrument for defining how nurses value the
      chosen nursing care goals.

PMID- 8291168
TI  - [Good nursing care--an important factor for patients' well-being and
      satisfaction].

PMID- 8291169
TI  - [Ethical perspectives in not giving extremely underweight infants a chance to
      live].

PMID- 8291170
TI  - [Does nursing count?].

PMID- 8291171
TI  - [Quality of nursing care seen from the Scandinavian nurse's viewpoint].
AB  - The aim of this study was to do the nurses' perception of quality of care
      explicit and to describe the quality of nursing from the nurses' perspective
      using a grounded theory approach. Sixteen nurses in four Nordic countries were
      interviewed. On the basis of the analysis a system theoretical model was
      generated. In the model there is a core category: patient focused outcome, and
      three mutual dependent categories; nursing capacity, organisation and physical
      environment. These categories are dynamically interrelated with the categories,
      relation and knowing the patient. The model is discussed in relation to relevant
      theories.

PMID- 8291172
TI  - Escherichia coli isolated from farm animals in England and Wales between 1986 and
      1991.
AB  - Escherichia coli isolated from farm animals in England and Wales between 1986 and
      1991 were examined for their serogroup, fimbrial adhesin and toxin production,
      and resistance to antimicrobial drugs. Among the 3595 porcine isolates the more
      common serogroups were O149, O8, O138, O147 and O157. The F4(K88) adhesin was
      detected in 21 per cent of the cultures, whereas the other adhesins were never
      present in more than 3 per cent during any year, although there was an upward
      trend in the prevalence of the F6(987P) antigen. The heat labile enterotoxin was
      produced by more than 17 per cent of the cultures usually in association with the
      F4 antigen. The other toxins, heat stable (STa), verocytotoxin (VT) and cytotoxic
      necrotising factor (CNF) were produced by 5.3, 4.7 and 6.8 per cent of the
      cultures, respectively. Among the 1383 bovine cultures the more common serogroups
      were O8, O101 and O17. The F5(K99) adhesin was detected in 9.1 per cent of the
      cultures, usually in association with STa production. The toxins STa, VT and CNF
      were produced by 4.4, 2.8 and 8.3 per cent of the cultures, respectively. Among
      the 407 ovine isolates the more common serogroups were O8, O101 and O78, and 11
      per cent of the cultures produced the F5(K99) antigen. The toxins STa, VT and CNF
      were produced by 1.5, 6.1 and 9.1 per cent of the cultures, respectively. In the
      case of the 402 poultry isolates the more common serogroups were O78, O2 and O8,
      which are usually associated with colisepticaemia. Resistance to antibiotics was
      common, particularly among the bovine isolates.

PMID- 8291173
TI  - Use of a stapling device to aid in the ovariectomy of nine mares with a granulosa
      thecal cell tumour.
AB  - This paper describes the use of a linear stapling device as an aid to unilateral
      ovariectomy in nine mares with granulosa thecal cell tumours. The intraoperative
      and postoperative complications are described and follow up details on each case
      are presented.

PMID- 8291174
TI  - Mutual resistance to avermectins and milbemycins: oral activity of ivermectin and
      moxidectin against ivermectin-resistant and susceptible nematodes.
AB  - To determine whether there is mutual resistance to avermectin and milbemycin
      anthelmintics, ivermectin and moxidectin sheep drenches were tested against
      ivermectin-resistant and susceptible isolates of Ostertagia circumcincta and
      Trichostrongylus colubriformis in sheep. None of the isolates had been exposed to
      moxidectin previously. The dosage of ivermectin required to remove 95 per cent of
      the ivermectin-resistant O circumcincta and T colubriformis were 23 times and six
      times larger, respectively, than the dosages required to remove the same
      percentage of susceptible isolates. The dosages of moxidectin required to remove
      95 per cent of the ivermectin-resistant O circumcincta and T colubriformis were
      31 times and nine times larger, respectively, than the dosages required to remove
      the same percentage of susceptible isolates. It is concluded that the worms
      resistant to ivermectin were also resistant to moxidectin.

PMID- 8291175
TI  - An unusual familial neurological syndrome in newborn thoroughbred foals.

PMID- 8291176
TI  - Cyclic behaviour of foot-and-mouth disease in India.

PMID- 8291177
TI  - Plasma free fatty acid concentration in control and lame sheep.

PMID- 8291178
TI  - Veterinary nursing examinations.

PMID- 8291179
TI  - Veterinary histopathology.

PMID- 8291180
TI  - Equine pharmaceutical products.

PMID- 8291181
TI  - Salmonella pullorum infection and pheasants.

PMID- 8291182
TI  - Suspected poisoning of two dogs.

PMID- 8291183
TI  - Variation in sensitivity of Trypanosoma congolense to diminazene during the early
      phase of tsetse-transmitted infection in goats.
AB  - Twenty-five goats were randomly allocated to five groups of five animals each and
      infected with Trypanosoma congolense IL 3274 via the bites of infected Glossina
      morsitans centralis. At intervals of 1, 4, 8, 12 or 19 days following infection,
      each group of five animals was treated intramuscularly with diminazene aceturate
      at a dose of 7.0 mg kg-1 body weight (b.w.). While treatment on Day 1 eliminated
      infections in all five goats, treatment on Day 19 did not cure any of the
      animals; in groups treated 4, 8 or 12 days following infection, two of five goats
      in each group were cured. Since the alteration in apparent resistance of T.
      congolense IL 3274 between Day 1 and Day 19 could have been due to alteration in
      expression of drug resistance by trypanosomes as the population expanded, the
      experiment was repeated using trypanosomes that reappeared in the animals that
      had been treated with diminazene aceturate on Day 19. On Day 36, when all five
      animals were parasitaemic, five groups of teneral G. m. centralis, each
      containing 160 flies, were fed on one occasion on each of the five goats (one
      group of testse flies per goat). Thereafter, each group of tsetse flies was
      maintained on clean rabbits. When infective, five flies from each group were
      allowed to feed on two naive goats each (i.e. two goats per group of tsetse
      flies). One animal in each pair was treated 24 h after infection with diminazene
      aceturate at a dose of 7.0 mg kg-1 b.w., the other was treated on Day 19, when
      parasitaemic, with the same drug dosage. As before, treatment 24 h following
      infection eliminated infections in all animals, but when treatment was delayed
      until Day 19, trypanosomes in all animals were refractory to treatment. Thus,
      although tsetse flies were infected with trypanosomes that had arisen in infected
      goats following treatment with diminazene aceturate at a dose of 7.0 mg kg-1
      b.w., when the same flies were allowed to feed on clean goats, the resultant
      infections were sensitive to treatment with the same drug dosage when
      administered 24 h following infection. These data therefore indicate that there
      is a significant alteration in diminazene sensitivity of IL 3274 between Day 1
      and Day 19 and that this is associated with an alteration in the resistance
      phenotype of the trypanosomes.

PMID- 8291184
TI  - Natural infections of Strongyloides westeri: prevalence in horse foals on several
      farms in central Kentucky in 1992.
AB  - During the period 28 February-1 July 1992, fecal samples were collected and
      examined for eggs of Strongyloides westeri once from each of 382 horse foals (364
      Thoroughbreds, 16 Standardbreds, one Lippizaner, and one draft-type horse) in
      central Kentucky. Ages of the foals at the time of sampling ranged from 7 to 63
      days (mean 22 days). The nine farms in the study were considered to have overall
      excellent deworming programs. None of the foals had been treated with an
      antiparasitic compound before the study. Eggs of S. westeri were found in 6% (22
      of 382) of the foals on 78% (7 of 9) of the farms. Current prevalence of this
      parasite in foals is discussed relative to studies before the availability and
      usage of effective drugs.

PMID- 8291185
TI  - Acute or chronic administration of prolactin alters ovine infections of
      Haemonchus contortus.
AB  - Prolactin has been implicated as a modulator in the phenomenon of periparturient
      egg rise during ovine nematodiasis. In the first experiment, lambs (4 months of
      age) with patent infections (10,000 infective larvae) of Haemonchus contortus
      were injected daily (Days 28-39 post-inoculation (PI)) with prolactin (20 or 200
      IU) or saline. Fecal egg concentrations and total daily egg production were
      monitored for each lamb. After 12 days, lambs injected with the lower dose of
      prolactin had the highest daily egg production. Fewer adult worms were collected
      from prolactin-treated lambs, and the female worms were larger than those from
      the saline-injected controls. Worm size and number were not correlated. In the
      second experiment, lambs were injected daily with ovine prolactin (25 IU) or
      saline. Five days after initiation of treatments, each lamb was inoculated with
      3000 infective larvae of H. contortus. After 42 days of injections (Day 37 PI),
      prolactin-treated lambs had larger and fewer worms, with higher fecundity, than
      saline-treated controls. Increases in endogenous circulating prolactin during
      late pregnancy and lactation in ewes, therefore, might contribute to
      periparturient egg rise irrespective of the developmental stage of the parasite
      when the hormone exposure occurs.

PMID- 8291186
TI  - The efficacy and persistent anthelmintic effect of ivermectin in sheep.
AB  - The direct efficacy and the long-term persistent anthelmintic effect of an oral
      suspension and an injectable formulation of ivermectin at a dose rate of 0.2 mg
      kg-1 was studied in sheep. Lambs were infected experimentally with Haemonchus
      contortus, Trichostrongylus vitrinus and Cooperia curticei. After 3 weeks they
      were treated with an oral suspension or with an injection, and reinfected with
      the same dose of larvae 3, 6 or 10 days after treatment. Post-mortem worm counts
      showed no persistent effect of the oral suspension. The injectable formulation
      showed an excellent persistent effect for up to 10 days against H. contortus.
      Reinfection with C. curticei 3 days after treatment resulted in a 64% reduction
      of the worm burden, but reinfection after 6 and 10 days was 100% reduced. The
      reduction of T. vitrinus was 46% after 3 days and 92% after 6 and 10 days.

PMID- 8291187
TI  - On the transmissibility of Eperythrozoon suis by Stomoxys calcitrans and Aedes
      aegypti.
AB  - The stable fly, Stomoxys calcitrans (Linnaeus), and the yellow fever mosquito,
      Aedes aegypti (Linnaeus), were utilized to determine their capability to transmit
      Eperythrozoon suis Splitter between swine. Three groups of each insect in each
      trial were allowed to feed on a pig previously infected with E. suis and then
      transferred to susceptible splenectomized pigs. As a control, one group of each
      insect was fed on a non-infected pig and then transferred to a susceptible pig.
      Stable flies were transferred immediately and following a delay of 1, 4, 24 h and
      7 days. Aedes aegypti were transferred immediately and following a 7 day delay.
      Successful transmission was accomplished in three of 15 pigs to which stable
      flies were transferred immediately and in nine of nine pigs to which A. aegypti
      were transferred immediately. No pigs became infected when there was a delay
      before transfer to the susceptible pig. All controls remained non-infected. This
      indicates that the stable fly and A. aegypti are likely to be mechanical vectors
      of E. suis under natural conditions. Differences in vector efficiency may be due
      to differences in mechanisms of blood-feeding which could affect the placement of
      the inoculum of E. suis.

PMID- 8291188
TI  - Trypanosoma evansi infection in dogs: seasonal prevalence and chemotherapy.
AB  - A 1-year survey was undertaken to determine the incidence of Trypanosoma evansi
      in dogs at Ludhiana, India. Of 64 dogs examined by wet film, thin smear, thick
      smear and mouse inoculation, three (4.68%) were found to be positive for T.
      evansi. All the positive animals were detected during the rainy and post-rainy
      seasons. The treatment of three infected dogs with a combination of quinpyramine
      sulphate and chloride (3:2 w/w) resulted in complete recovery of two dogs;
      another dog died on the day therapy was initiated.

PMID- 8291189
TI  - A colorimetric assay for trypanosome viability and metabolic function.
AB  - We have adapted a tetrazolium salt (MTT) colorimetric cytotoxicity assay to the
      assessment of viability and metabolic function in cultured African trypanosomes.
      Trypomastigotes of Trypanosoma congolense and T. brucei rhodesianse were
      harvested from the blood of parasitemic rats and cultured under axenic conditions
      that support trypanosome viability and growth. Analysis of serial dilutions of
      these bloodstream forms indicated that the assay could detect 10(4) parasites. To
      assess the effect of lymphoid cytokines on trypomastigote viability, 10(5)
      freshly harvested parasites were cultured with a wide range of dilutions of human
      recombinant IL-1, IL-3, IL-6, interferon-gamma (IFN gamma) or tumor necrosis
      factor-alpha (TNF alpha), or bovine recombinant IFN gamma or TNF alpha for 24, 48
      or 96 h. These cytokines had no apparent growth enhancing or inhibitory effect on
      the trypomastigotes compared with growth in supplemented medium alone. This assay
      has several advantages over traditional counting methods, including increased
      sensitivity and rapid, repeatable quantitation. This adaptation of the MTT
      colorimetric assay should be useful in screening drugs and host-derived factors
      for growth-modulating effects on trypanosomes and other extracellular protozoan
      parasites.

PMID- 8291190
TI  - Evaluation of the efficacy of a slow release device containing homidium bromide
      in rabbits infected with Trypanosoma congolense.
AB  - The subcutaneous implantation of a slow release device (SRD) containing 1 mg kg-1
      homidium bromide (Ethidium) protected 95% of the rabbits for at least 3 months
      against reinfection with different stocks of Trypanosoma congolense. Only 30.8%
      of the animals, which received the classical intramuscular injection of 1 mg kg-1
      homidium bromide, were protected for more than 1 month. The advantages of an SRD
      against injection of homidium bromide are a longer protection period, less
      variation in the percentage of protected animals and the possibility to recover
      the implants at slaughter. The possible effects on the development of resistance
      have to be examined further.

PMID- 8291191
TI  - Use of reseeded pastures as an aid in the control of gastrointestinal nematodes.
AB  - The degree of nematode infectivity of a previously contaminated pasture which was
      reseeded after harvesting of a soya bean crop was determined by use of four
      tracer lambs and four tracer calves. The eight tracers were put to graze for 14
      days and housed for another 14 days before being slaughtered, when faeces and the
      intestinal tracts were examined for worm eggs and parasites. With the exception
      of one animal, which was found to be harbouring 20 Cooperia punctata, the tracers
      had no adult or immature nematodes. The implications of the use of such pastures
      are discussed in relation to their possible role in parasite control and
      anthelmintic resistance in Brazil.

PMID- 8291192
TI  - SDS-PAGE profiles of somatic proteins from third-stage infective larvae of
      Ostertagia ostertagi and Cooperia oncophora.
AB  - Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) profiles of
      somatic proteins from third-stage infective larvae of Ostertagia ostertagi and
      Cooperia oncophora were evaluated using laser densitometry. Several protein bands
      were present from both parasite preparations. A few bands from each parasite
      appeared to be unique. Purification of these proteins for use in serologic
      monitoring of cattle naturally infected with O. ostertagi and C. oncophora should
      allow circumvention of cross-reactivity between the two genera, which has been
      reported by others.

PMID- 8291193
TI  - Seasonal prevalence of Cephalopina titillator myiasis in camels (Camelus
      dromedarius) in Sokoto State, Nigeria.

PMID- 8291194
TI  - The effect of trypanocidal drug treatment on the haematological changes in
      Trypanosoma brucei brucei infected splenectomised dogs.
AB  - Twenty adult mongrel dogs of both sexes were used. Ten of the dogs were
      splenectomised and the remaining dogs were left intact. Five dogs each from the
      splenectomised and non-splenectomised (intact) animals were infected
      intravenously with Trypanosoma brucei brucei while the rest served as uninfected
      controls. All the infected dogs developed trypanosomosis between Days 4 and 8
      postinfection. The packed cell volume, haemoglobin concentration, total red blood
      cell count and white blood cell count decreased progressively indicating anaemia
      and leucopenia. The absolute reticulocyte counts were increased. Splenectomy
      enhanced fever, reticulocytosis and parasitaemia but delayed the onset of anaemia
      and leucopenia. It also shortened the prepatent period of the infection. The
      treatment of the infected dogs with diminazene aceturate (Berenil at the dose
      rate of 7.0 mg kg-1 body weight on Day 21 postinfection cleared the parasites in
      blood within 24 h and resulted in complete reversal of all the haematological
      aberrations observed. Splenectomy did not enhance or inhibit the recovery rate in
      the animals after treatment.

PMID- 8291195
TI  - Detection of Cryptosporidium parvum using a specific polymerase chain reaction.
AB  - The design and use of polymerase chain reaction primers and probes as reagents
      for the detection of Cryptosporidium parvum are described. Sensitive and specific
      amplification of a 329 base pair product was demonstrated by ethidium bromide
      staining and hybridisation of radiolabelled probes. These reagents have the
      potential for application to diagnostic samples, environmental monitoring and
      epidemiological surveys.

PMID- 8291196
TI  - Serum antibody response in lambs naturally and experimentally infected with
      Cryptosporidium parvum.
AB  - The immunoglobulin (IgG), IgM and IgA responses in Castellana-Manchega cross-bred
      colostrum-deprived and colostrum-fed lambs infected neonatally with
      Cryptosporidium parvum were measured using an enzyme-linked immunosorbent assay.
      A comparison of oocyst shedding and anti-C. parvum serum IgG levels in lambs
      suffering either natural or experimental infection was undertaken. Effects on the
      oocyst shedding and IgG levels of C. parvum rechallenge at 30 and 120 days of age
      in neonatally infected lambs were also evaluated. Anti-C. parvum immunoglobulin
      levels in colostrum-deprived animals peaked on Day 30 of life for IgG and on Day
      15 for IgM and IgA. Lambs that received maternal colostrum showed elevated anti
      C. parvum IgG, IgM and IgA levels at 3 days old indicating a transfer of
      colostral immunoglobulins. Experimentally infected lambs showed a IgG response
      similar to naturally infected lambs, suggesting that the serum IgG response is
      independent of the infective dose. Finally, lambs rechallenged at 30 and 120 days
      old did not show either appreciable oocyst shedding or any increase in their anti
      C. parvum IgG levels when compared with prechallenged animals.

PMID- 8291197
TI  - Experimental modes of Caryospora bigenetica (Apicomplexa: Eimeriidae) infection
      in swine and the effects of temperature and salinity on parasite infectivity in
      porcine tissue.
AB  - Four crossbred pigs (Sus scrofa) were inoculated orally with Caryospora
      bigenetica oocysts derived from snake and mouse feces, and with C. bigenetica
      infected mouse tissue. One pig also was given i.m. injections of
      methylprednisolone acetate. All four pigs displayed clinical signs including
      erythema, edema, and lethargy. Caryocysts were observed histologically in
      numerous tissues including ear, tongue, jowl, shoulder, loin, intercostal, ham,
      hock, and feet. The four pigs each were butchered into six commercial cuts:
      shoulder, loin, side, ham, hock, and feet. Raw 10 g samples from each cut were
      bioassayed by pepsin digestion and s.c. inoculation into 12 Swiss-Webster mice
      (Mus musculus) and 12 cotton rats (Sigmodon hispidus). Seventeen of 24 mice and
      cotton rats exhibited clinical signs and C. bigenetica tissue infections.
      Remaining portions of the six commercial cuts were temperature or saline treated,
      and 10 g samples were bioassayed in 16 mice and 12 cotton rats. No clinical sign
      or tissue infection was observed in these animals. Our study presents evidence
      that swine can be infected with C. bigenetica by ingesting oocysts present in
      snake feces or mouse feces (following inoculation of mice with snake-derived
      oocysts) or by ingesting C. bigenetica infected rodent tissue, that endogenously
      produced C. bigenetica oocysts are not excreted in the feces of swine, and that
      C. bigenetica in pork can be rendered noninfective by freezing at -20 degrees C (
      4 degrees F) for 21 days, frying at 84 degrees C (183 degrees F) for 17 min,
      microwaving at 88 degrees C (190 degrees F) for 17 min, grilling at 82 degrees C
      (180 degrees F) for 48 min, baking at 95 degrees C (203 degrees F) for 230 min,
      boiling at 100 degrees C (212 degrees F) for 60 min, or by curing at 4 degrees C
      (39 degrees F) for 20 days.

PMID- 8291198
TI  - Multiplex polymerase chain reaction based assay for the detection of Babesia
      bigemina, Babesia bovis and Anaplasma marginale DNA in bovine blood.
AB  - A highly sensitive polymerase chain reaction (PCR) based method was developed to
      detect, in the same blood sample, DNA of hemoparasites frequently found together
      infecting cattle in tropical and subtropical areas. Bovine blood containing equal
      parasitemias of Babesia bigemina, B. bovis and Anaplasma marginale infected
      erythrocytes was mixed to standardize the test. Twenty microliters of 10-fold
      dilutions from the pooled blood sample were resuspended in PCR mixture buffer
      containing each of the species-specific sets of primers. Group I primers
      (BiIA/IB, BoF/R and Am9/10) which specifically bind B. bigemina, B. bovis and A.
      marginale DNA were used to amplify a fragment of DNA from genomic parasite DNA.
      Group II nested primers (BiIAN/IBN, BoFN/RN and Am11/12) were used to prepare,
      via incorporation of digoxigenin-11-dUTP by PCR, nonradioactive probes specific
      for internal sequences present in DNA amplified with Group I primers. Agarose gel
      electrophoresis and Southern blot hybridization studies showed that by using
      Group I primers, DNA fragments of 278 bp, 350 bp and 200 bp were specifically
      amplified in samples containing B. bigemina, B. bovis and A. marginale DNA,
      respectively. The analytical sensitivity of the multiple PCR test, as evaluated
      by nucleic acid hybridization with the nonradioactive probe, was 0.00001%,
      0.00001% and 0.0001% infected erythrocytes for B. bigemina, B. bovis and A.
      marginale, respectively. Blood collected from cattle previously inoculated with
      B. bovis (4 years), A. marginale (2 years) and B. bigemina (1 year) was
      demonstrated to be latently infected by using the Multiplex PCR test.

PMID- 8291199
TI  - Ultrastructure of Hepatozoon canis in the dog.
AB  - The ultrastructure of several stages of Hepatozoon canis found in dogs with
      clinically diagnosed infections was determined using transmission electron
      microscopy. Stages were found in skeletal muscle tissue that corresponded to the
      'onion skin' cyst stage, as described at the light microscopic level, and were
      composed of an electron-transparent material that appeared to radiate from a
      central core. Larger cysts, walled off by fibroblasts, contained a transformed
      host cell located centrally within them. The parasitic stage within these
      transformed cells contained numerous organelles including mitochondria and Golgi
      apparatus, and was singularly nucleated. In cardiac muscle, a meront was observed
      which produced merozoites by ectomerogony. Adjacent to this meront was a
      granuloma containing merozoites within mononuclear phagocytes which may either
      serve as a reservoir of parasites for reinfection of the host or differentiate
      into the circulating gamont stage of the parasite. Gamonts were found within
      parasitophorous vacuoles inside circulating neutrophils. They had a condensed
      cytoplasmic appearance and were extremely electron dense with respect to other
      observed parasite stages. In vitro cultivation of parasitized neutrophils
      resulted in the appearance of a stage of the parasite with altered ultrastructure
      compared with gamonts found in circulating neutrophils. This stage was judged to
      be a possible gamete stage of the parasite.

PMID- 8291200
TI  - Local and systemic antibody production in horses affected with chronic
      obstructive pulmonary disease.
AB  - An enzyme-linked immunosorbent assay (ELISA) was used to quantify isotype
      specific antibody to Micropolyspora faeni and to Aspergillus fumigatus in the
      sera and bronchoalveolar lavage fluid (BALF) of normal horses, horses with
      chronic obstructive pulmonary disease (COPD) and horses with other chronic
      respiratory diseases. Elevated antibody levels were not detected in the sera of
      affected horses. However, both IgE and IgA antibody to both allergens was
      significantly elevated in BALF in COPD affected horses sampled both when
      symptomatic and asymptomatic. Elevated levels were also found in animals that
      developed a chronic cough after an acute onset with symptoms compatible with a
      respiratory virus infection. In one animal a ten fold increase in IgE antibody to
      the two allergens developed after an interval of 7 weeks. These findings are
      supportive of a central role of local IgE antibody to mould allergens in the
      immunopathogenesis of COPD, and also suggest that respiratory viral infection may
      predispose to the development of COPD in some horses.

PMID- 8291201
TI  - Immunologic studies of a horse with lymphosarcoma.
AB  - Immunological, clinical, and pathological investigations were conducted on a
      horse with lymphosarcoma. The immunological status was investigated by measuring
      the level of antibodies by single radial immunodiffusion test and the ability of
      lymphocytes to proliferate in response to mitogens. Multiple immunological
      abnormalities were noted in this horse. They were; (1) decreased IgM, IgG, and
      IgA levels in the serum despite hyperproteinemia; (2) increased in-vitro
      spontaneous lymphoproliferation which reflects augmented mitosis; (3) decreased
      lymphoproliferative response to T cell stimulants (e.g. Concanavalin-A (Con-A))
      suggesting impaired T cell activation; (4) presence of immunosuppressive factors
      in serum as demonstrated by in-vitro lymphocyte culture systems. Clinical
      pathology findings revealed an unusual monoclonal alpha peak in the serum and
      morphologically abnormal lymphocytes distributed throughout the body. Serum
      fractionated by fast protein liquid chromatography (FPLC) revealed that the
      immunosuppressive factors were found in this abnormal alpha peak. The
      immunopathological findings in this horse are discussed.

PMID- 8291202
TI  - Acute phase response to Salmonella in a pig liver perfusion model.
AB  - Livers from 7- to 14-day old pigs were maintained on a perfusion apparatus for 3
      h. The perfused livers maintained physiologic and immunologic functions during
      perfusion. The perfused livers retained 78-94% of a non-recirculating inoculum of
      approximately 1-5 x 10(8) Salmonella choleraesuis (Scs), and cleared 94.9 +/-
      1.7% of the retained (Scs) during the 3-h perfusion period. When the acute phase
      response (APR) was induced in liver donor pigs 24 h before liver perfusion, the
      perfused livers had diminished capability to retain, and greatly diminished
      capability to clear Scs. When sterile, filtered, and concentrated liver perfusate
      (LP) from previous, LPS-perfused livers was added to the perfusion fluid (PF) at
      50 min of Scs perfusion (passive APR), Scs clearance was inhibited. When sterile,
      filtered LP from previously Scs perfused livers was added to the system, liver
      clearance was abolished, and Scs always grew in such livers during the 3 h
      perfusion period. The LP of livers perfused with Scs enhanced growth of Scs in an
      in vitro assay. These observations suggest that products of the acute phase
      response favor growth of Scs in vitro and in vivo.

PMID- 8291203
TI  - Increased levels of tumor necrosis factor and interleukin 1 in bronchoalveolar
      lavage fluids from pigs infected with Mycoplasma hyopneumoniae.
AB  - We examined the levels of tumor necrosis factor (TNF)-alpha and interleukin-1 (IL
      1) in bronchoalveolar lavage fluids (BALF) from pigs experimentally infected with
      Mycoplasma hyopneumoniae using biological assays with WEHI-164 cells and D10.G4.1
      cells, respectively. Increased TNF-alpha and IL-1 in BALF were found in infected
      pigs with gross and/or microscopic lesions. A time-course study suggested TNF
      alpha and IL-1 to be persistently elevated in infected pigs. Their presence in
      BALF would thus appear to be associated with the development of pneumonic lesions
      in M. hyopneumoniae infected pigs.

PMID- 8291204
TI  - Isolation and purification of bovine myeloperoxidase from neutrophil granules.
AB  - Bovine myeloperoxidase (MPO) was isolated and purified from neutrophil granules
      using protein extraction at pH 4 and gel filtration combined with fast protein
      liquid chromatography. The extracted protein was identified as MPO based on its
      absorption spectrum, amino acid composition, peroxidase activity and polypeptide
      structure. Bovine neutrophils contained three different forms of MPO (I, II and
      III). When subjected to sodium dodecyl sulphate polyacrylamide gel
      electrophoresis each of the three purified forms showed two distinct bands
      corresponding to heavy and light polypeptide chains of approximately 57,000 and
      15,000 molecular radius. Amino acid analysis of the three forms showed that there
      was an overall similarity between them. Slight differences were found between MPO
      Form III and the other two forms. The three forms of bovine MPO were shown to
      differ in their specific enzyme activities in a luminol-dependent
      chemiluminescence assay. MPO Form III showed the highest enzyme activity. The
      amount recovered during purification of the respective MPO forms varied, with the
      recovery being highest for MPO I. Our findings suggest that there are intrinsic
      differences between the three forms of bovine MPO. In terms of their amino acid
      composition and molecular weight, the bovine MPO closely resembled human and
      canine MPO.

PMID- 8291205
TI  - Expression of an evolutionarily conserved function associated molecule on sheep,
      horse and cattle natural killer cells.
AB  - Natural killer (NK) cells are large granular lymphocytes that lyse a wide variety
      of transformed and virally-infected target cells without prior exposure to
      antigen, and without restriction by major histocompatibility complex antigens.
      Although NK cells have been identified in a variety of mammalian species, how NK
      cells recognize antigen and trigger lysis is unknown. Recently, monoclonal
      antibodies made against NK-like cells from teleost fish were shown to react with
      NK cells from humans and rats, and to inhibit their cytolytic activity. The role
      of this apparently evolutionarily conserved function-associated molecule (FAM)
      has been further investigated utilizing a variety of domesticated farm animal
      species. It was observed that the anti-FAM mAb reacted specifically with
      peripheral blood lymphocytes isolated from sheep, horses and cattle. Further, the
      anti-FAM mAb inhibited NK cell lytic activity in each of these species. Finally,
      the anti-FAM mAb was found to inhibit conjugate formation between NK and target
      cells, implying that the FAM was involved in antigen recognition by NK cells in
      each of these species. In conclusion, it appears that NK cell function is
      mediated by an evolutionarily conserved FAM in a wide variety of species.

PMID- 8291206
TI  - Alloantibodies against A and B blood types in cats.
AB  - This study characterizes the naturally occurring feline alloantibodies against A
      and B blood type. All examined type-A and type-B cats had naturally occurring
      antibodies against erythrocytes of the opposite blood type. In order to determine
      the class of immunoglobulins, sera from cats were analyzed using incubation with
      2-mercaptoethanol (2-ME), immunoprecipitation, and gel filtration. Type-A cats
      had weak agglutinins of the IgM class and weak hemolysins which consisted of
      approximately equal parts of IgG and IgM class. Type-B cats had strong
      hemagglutinins and hemolysins mostly of the IgM class. Colostral antibodies were
      detectable in newborns as early as 4 h after birth and their own alloantibody
      production started at 6-8 weeks of age. The presence of naturally occurring
      alloantibodies, in particular the anti-A alloantibodies, renders cats susceptible
      to clinical incompatibility reactions.

PMID- 8291207
TI  - Canine neutrophil adhesion proteins and Fc-receptors in healthy dogs and dogs
      with adhesion protein deficiency, as studied by flow cytometry.
AB  - Murine monoclonal anti-human antibodies directed against neutrophil adhesion
      protein receptors CD35, CD18, CD11b, CD11c and the Fc-receptors CD64 (Fc gamma
      RI), CD32 (FC gamma RII) and CD16 (Fc gamma RIII) were evaluated regarding their
      ability to bind to the canine homologues. The antibodies against CD35, CD18,
      CD11b, CD11c and CD16 could be used to evaluate the expression of canine
      homologues. The routine of using frozen cells and thereby avoiding methodological
      errors, when samples are stained at different times, was evaluated by comparison
      of receptor expression in frozen and fresh samples from the same dogs. All
      receptors were expressed consistently on the cell surface on frozen and fresh
      neutrophils with the exception of CD16, which showed decreased expression in
      frozen cells. The expression of CD11c on neutrophils from dogs with canine
      leucocyte adhesion deficiency (CLAD) was analyzed and there was no difference in
      receptor expression between CLAD-puppies and healthy controls. CD11b/CD18
      expression on neutrophil samples from three parents of CLAD-puppies, i.e.
      heterozygotes, did not differ from receptor expression in normal controls.
      Analysis of the Fc-receptor expression on neutrophils from CLAD-puppies showed
      that the expression of CD16 tended to be decreased in patients compared with
      controls.

PMID- 8291208
TI  - Identification and characterization of a mouse monoclonal antibody (M10) directed
      against canine (dog) CD8+ lymphocytes.
AB  - Monoclonal antibodies (mAb) were produced by immunizing BALB/c mice with non
      adherent dog lymphocytes. M10 was specific for a subset of dog lymphocytes. M10
      belonged to the IgG1 subclass and reacted with 26% of dog peripheral blood
      lymphocytes, 24% of spleen lymphocytes, 81% of thymus cells, 1.2% of bone marrow
      cells (5.8% of bone marrow lymphocytes) and 23% of PHA-stimulated lymphocytes.
      Immunohistology of snap-frozen thymus and spleen showed that the spleen B-cell
      area stained negative, whereas the spleen T-cell area and the thymus medulla
      exhibited positive reaction in 20-30%. The thymus cortex was strongly positive.
      M10 diminished cell lysis by 58% in cell mediated lysis assays (CML). Immunoblot
      assays revealed that M10 recognized an antigen with a molecular weight of 76 kD
      under non-reducing and 33 kD under reducing conditions. Finally, M10 bound to a
      canine CD8 alpha transfected rat T-cell line (NB2). These findings characterize
      M10 as an antibody directed against the dog CD8 antigen.

PMID- 8291209
TI  - Protective oral immunization of chickens against Eimeria tenella with sporozoite
      surface antigens.
AB  - Antigens were extracted from the surface of Eimeria tenella sporozoites with a
      solution containing Triton X 100 (1%), sodium dodecyl sulphate (0.5%) Na
      deoxycholate (1%) and EDTA (1 mM). After removal of the detergents, these surface
      antigen preparations conferred an immunity that protected chickens against a
      subsequent infection (10(4) sporulated oocysts). The best results were obtained
      after two 250 micrograms injections of Al(OH)3 adsorbed antigens (oocyst output
      per g caecal material on Day 7 post infection: 2.39 x 10(7) +/- 0.32 x 10(7)
      oocysts for controls and 7.37 +/- 10(6) +/- 3.19 x 10(6) oocysts for vaccinated
      birds) and after four gastric intubations of liposome entrapped antigens (oocysts
      output on Day 7 postinfection: 2.75 x 10(6) +/- 2.02 x 10(6) g-1 caecal
      material). These results represented respectively 70 and 88% protection indexes.
      Studies on the systemic and local antibody response after one or several
      infections of chickens with the parasite indicated at least 20 different
      molecules in the detergent antigens which are classified after immunoblotting
      according to their properties.

PMID- 8291210
TI  - Localized leucocyte response to Ichthyophthirius multifiliis establishment in
      immune carp Cyprinus carpio L.
AB  - O-group carp (Cyprinus carpio) which had been immunized against Ichthyophthirius
      multifiliis by controlled infections were challenged by topical application of
      theronts to the caudal fin. The parasites which established were examined
      ultrastructurally, and host leucocyte responses were compared with those observed
      in primary infections. In the primary exposure group eosinophils and (to a lesser
      extent) basophils were the predominant cells infiltrating infection sites. In
      contrast, parasite development in immunized fish initiated localized leucocytic
      infiltrations which were dominated by eosinophilic granular cells (EGCs) and
      basophils. Greater localized phagocytosis was recorded in immunized fish by
      neutrophils, macrophages and resident epidermal filament cells. In vitro studies
      indicated that pronephric leucocytes from immunized fish displayed enhanced non
      specific phagocytosis. In the skin, leucocytes were observed in close proximity
      to the trophozoite surface in both immunized and primary exposure fish, often
      undergoing lysis and release of cellular contents. However, there was no evidence
      of active cell adherence nor of any cell-mediated damage incurred to the parasite
      in either case. These observations are discussed in relation to the possible role
      of leucocytes in mediating pathogenesis and immune responses.

PMID- 8291211
TI  - Effect of costimulants on interleukin-2-like activities from goat peripheral
      blood mononuclear cells.
AB  - Culture supernatants containing interleukin-2-like activities (CS-IL2) were
      prepared from goat peripheral blood cells (mononuclear cells 75% and
      polymorphonuclear cells 25%). These were stimulated with three costimulants,
      (tetradecanoyl phorbol acetate, indomethacin and calcium ionophore A23187),
      either alone or in different combinations, in RPMI-1640 medium (containing 0.5%
      bovine serum albumin (BSA)) with or without serum. After 18 h of incubation with
      costimulants, concanavalin A (Con A) was added and the incubation was continued
      for next 48 h. Higher interleukin-2 (IL-2)-like activities were generated in the
      culture supernatants prepared in RPMI-1640 growth medium containing 0.5% BSA
      without serum. Further, IL-2-like activities were much higher in culture
      supernatants obtained by stimulation with all the three costimulants, as well as
      Con A, than the two costimulants with Con A or any of the costimulants with Con
      A.

PMID- 8291213
TI  - Selection experiments to alter disease resistance traits in domestic animals.

PMID- 8291212
TI  - Avian CD Nomenclature Workshops, Montreal, June 1991, Budapest, August 1992 and
      Tours, September 1992.

PMID- 8291214
TI  - Alteration of the basement membrane in human thyroid diseases: an
      immunohistochemical study of type IV collagen, laminin and heparan sulphate
      proteoglycan.
AB  - Basement membrane (BM) alteration in thyroid diseases was examined by
      immunohistochemistry using antibodies for the three major BM proteins: type IV
      collagen, laminin and heparan sulphate proteoglycan. Linear epithelial BMs
      surrounding follicles accompanied by vascular BMs forming loops, similar to those
      seen in the normal thyroid, were observed in Graves' disease and adenomatous
      goitre. Hashimoto's thyroiditis showed scant epithelial BMs as a result of
      follicle destruction. In follicular adenomas, development of epithelial BMs
      seemed to be related to follicle formation; well-developed epithelial BMs were
      frequently seen in normo- or large-follicular type, whereas trabecular or solid
      types revealed scant or poorly developed epithelial BMs. Lumpy accumulation of BM
      proteins was detected in hyalinizing trabecular adenomas. Papillary carcinomas
      revealed two different types of papillae; one type contained both epithelial and
      vascular BMs, and the other had only vascular BMs. Epithelial BMs in invasive
      areas of papillary carcinoma were distributed in an irregular, interrupted
      manner, and were completely absent in many foci. Anaplastic carcinomas showed
      scant or a total loss of epithelial BMs. These results suggest that alterations
      of BM in thyroid diseases clearly reflect their architectural variations,
      presumably in connection with their function and/or biological behaviour.

PMID- 8291215
TI  - Expression of progesterone receptors in solid-cystic tumour of the pancreas: a
      clinicopathological and immunohistochemical study of ten cases.
AB  - A role for sex hormones in the pathogenesis of solid-cystic tumour (SCT) of the
      pancreas is suggested by its predilection for young fertile women. Controversial
      data have been provided for the presence of progesterone receptors (PR) and/or
      oestrogen receptors (ER) in SCT. We report the immunohistochemical detection of
      PR in ten cases of SCT. Eight were from young women. The remaining two were from
      a post-menopausal woman and a young boy. All cases showed PR immunoreactivity in
      the large majority of neoplastic cells, whereas none exhibited ER positivity. In
      one tumour two types of cell populations were noted, the more anaplastic invasive
      type being PR negative, whereas the more typical was PR positive. PR
      immunoreactivity in the absence of ER may simply reflect a lower sensitivity of
      ER antibody failing to reveal the biochemically detectable ER, or that the PR in
      cells of SCT are constitutively synthesized in an oestrogen-independent way, as
      in T47D breast carcinoma cell line, meningioma cells and some gastric cancer
      cells. Our findings support the hypothesis of a possible pathogenetic role of
      progesterone in SCT, independent of the patient's sex and age.

PMID- 8291216
TI  - Localization of T lymphocytes and macrophages expressing IL-1, IL-2 receptor, IL
      6 and TNF in human aortic intima. Role of cell-mediated immunity in human
      atherogenesis.
AB  - Recent observations have demonstrated the presence of activated T lymphocytes and
      macrophages in human atherosclerotic lesions. Cells found within these lesions
      produce cytokines that alter vascular homeostasis in a manner that promotes
      atherogenesis. To elucidate the role of these immunocompetent cells in human
      atherosclerosis, the localization of various cytokines with an analysis of
      immunophenotypic features of the cellular infiltrates was studied in normal
      aortas from children; and in later phases of the disease (including fatty streaks
      and fibrous or atheromatous plaques). Semi-quantitative analysis of cytokine
      expressing cells was also investigated with serial sectioning. In 4 of 9 young
      subjects, the grossly normal aorta contained relatively cell-rich areas which
      were located preferentially around the ostia of intercostal arteries and were
      composed of isolated or layered T lymphocytes and macrophages. In these
      prelesional areas, interleukin-1 (IL-1), IL-2 receptor (IL-2R) and tumour
      necrosis factor (TNF) were detected in the cytoplasm of the infiltrating cells,
      whereas no detectable reactivity was noted for IL-2, IL-6, interferon-gamma (IFN
      gamma) or lymphotoxin (LT). In fatty streaks and full-grown atheromas including
      "cap" and "shoulder" regions, various numbers of T lymphocytes, macrophages and
      macrophage foam cells were present. In these lesion areas, especially where the
      cellular infiltrates were numerous, macrophage foam cells and smooth muscle cells
      expressed not only IL-1 and TNF but also IL-6. The ratio of IL-2R positive cells
      showed a tendency to decrease with advance of the disease process. Electron
      microscopic examination of lesion areas demonstrated ultrastructural aspects of
      the cognate cell-to-cell interaction, as shown by the direct apposition of
      lymphocytes to macrophages or macrophage foam cells. These results suggest that a
      specific in situ, cell mediated hypersensitivity plays a pivotal role in the
      nascent as well as the progression stages of human atherosclerosis.

PMID- 8291217
TI  - Prognostic significance of p53 expression in relation to DNA ploidy in colorectal
      adenocarcinoma.
AB  - p53 expression, DNA ploidy and S-phase fraction were analysed retrospectively in
      colorectal adenocarcinomas from 293 patients in whom the long-term outcome was
      known. The frequency of nuclear p53 staining was increased in non-diploid tumours
      (42%) when compared with diploid tumours (33%). Cytoplasmic p53 positive tumours
      were more common in the proximal colon (32%) than in the distal sites (21%). In
      univariate survival analysis, nuclear p53 and cytoplasmic staining were
      significantly associated with poor prognosis in patients with Dukes' A-C tumours.
      The patients showing both nuclear and cytoplasmic p53 staining had the poorest
      survival and the patients with tumours negative in both the nucleus and cytoplasm
      showed the best prognosis. The patients with tumours positive in the nucleus
      alone or in the cytoplasm alone presented an intermediate survival. In
      multivariate survival analyses, nuclear p53 expression, cytoplasmic p53
      expression and DNA ploidy were prognostic indicators independent of Dukes' stage
      and each other. Further analysis suggested that the prognostic importance of
      cytoplasmic p53 expression was greater in diploid than in non-diploid tumours. We
      conclude that nuclear p53 expression, cytoplasmic p53 expression and DNA ploidy
      provide important prognostic information in colorectal adenocarcinomas.

PMID- 8291218
TI  - Establishment of a normal range of morphometric values for peroxisomes in
      paediatric liver.
AB  - The size and number of hepatic peroxisomes was investigated in 16 control
      paediatric liver biopsies from patients ranging in age from 3 months to 18 years
      one fetal liver specimen and one paediatric autopsy liver. The area, diameter,
      volume density (Vv), numerical density (Nv) and surface density (Sv) of the
      peroxisomes was recorded using randomly selected electron micrographs. The mean
      diameter of peroxisomes in control paediatric liver was 0.56 microns, the mean Vv
      was 1.67%, the mean Nv was 0.125 per micron+3 and the mean Sv was 0.161 per
      micron. No correlation was found between the size and number of hepatic
      peroxisomes and the age or sex of the patient. Peroxisomes in the fetal liver
      were smaller than those in biopsy tissue and had a mean diameter of 0.42 micron.
      Peroxisomes were identified in autopsy tissue and were enlarged with a mean
      diameter of 0.75 micron, most probably due to post-mortem swelling. A range of
      morphometric values in paediatric liver has now been established.

PMID- 8291219
TI  - Preservation time dependent morphological changes in cold stored human donor
      pancreas.
AB  - Pancreatic transplantation is being used to treat insulin-dependent diabetes. An
      intact structure of the graft is a prerequisite for preserved function and we
      therefore monitored the light microscopic and ultrastructural changes in 30 human
      donor pancreases stored in the cold in University of Wisconsin preservation
      solution. Twenty-three pancreases were stored for less than 24 h and 7 for more
      than 30 h. All glands stored longer than 30 h displayed cytoplasmic vacuolisation
      in a variable proportion of acinar cells. In addition, the glands stored over 40
      h showed focal acinar necrosis. Endocrine tissue was only slightly affected,
      while duct cells showed no changes. It is concluded that cold preserved
      pancreases stored for less than 24 h are best for transplantation purposes and
      that acinar cells are more sensitive to ischaemic damage than endocrine and duct
      cells.

PMID- 8291220
TI  - Selenium deficiency and fulvic acid supplementation induces fibrosis of cartilage
      and disturbs subchondral ossification in knee joints of mice: an animal model
      study of Kashin-Beck disease.
AB  - Kashin-Beck disease is an acquired, chronic and degenerative osteoarticular
      disorder. Selenium deficiency and fulvic acid in drinking water have been
      implicated in the cause of this disease. Pathologically, chondronecrosis of the
      growth plate and articular cartilage and subconsequent disturbance of
      ossification were observed in the joints. In this animal model study, mice were
      fed with a selenium deficient diet and fulvic acid supplemented drinking water
      for two generations. In undecalcified histological preparations of bone we
      carried out histological staining to detect mineralized and unmineralized bone
      and cartilage. The results revealed that selenium deficiency and fulvic acid
      supplementation induced degeneration of the articular cartilage in the knee
      joints of mice. Dynamic fluorescent labelling of ossification, enzyme
      histochemical detection of alkaline phosphatase activity in osteoblasts and a
      typical immunohistochemical localization of collagens type I and II indicated the
      development of fibrocartilage at the articular surface of knee joints, resembling
      the early stages of osteoarthrosis. This became obvious by disturbed development
      of the articular space and meniscus, markedly impaired formation of subchondral
      bone and early differentiation failure during enchondral ossification. This
      animal model provides an approach to study the molecular pathogenesis of Kashin
      Beck disease.

PMID- 8291221
TI  - Diagnostic tools for differentiating pleural mesothelioma from lung
      adenocarcinoma in paraffin embedded tissue. II. Design of an expert system and
      its application to the diagnosis of mesothelioma.
AB  - A panel of 14 antibodies (panepithelial antibody Lu-5, anti-keratin-18, anti
      keratin-7, Ber-EP4, anti-Leu-M1, HEA-125, anti-carcinoembryonic antigen, anti
      blood group-related antigens A, B, H, B72.3, anti-placental alkaline phosphatase,
      anti-vimentin and BMA-120), which have been evaluated for use in differentiating
      mesothelioma from lung adenocarcinoma, was applied to a group of 24 suspected
      mesotheliomas. Using the established qualitative, descriptive criteria derived
      from monovariate statistical analysis of the tumour control groups (definite
      mesotheliomas, adenocarcinomas), a definitive allocation was possible in only 25%
      of suspected cases. We therefore constructed two "expert systems", based on
      multivariate discriminant analysis with either the ALLOC 80 program for ordinal
      data or a newly developed analysis program for binomial data. With these two
      systems diagnostic allocation of suspected mesotheliomas was improved to 75% and
      79%. The use of binomial data ("positive" versus "negative") in conjunction with
      the probability-based test system is of particular interest because the primary
      data are easy to record and the test results have a higher statistical
      probability.

PMID- 8291222
TI  - Immunohistochemical profile of invasive lobular carcinoma of the breast:
      predominantly vimentin and p53 protein negative, cathepsin D and oestrogen
      receptor positive.
AB  - Vimentin, p53 protein and cathepsin D positivity were assessed by
      immunohistochemistry, and oestrogen receptor (ER) by an enzyme immunoassay, in
      invasive lobular carcinomas (LC) of the breast. While vimentin was positive in
      only 5% (3/57) and p53 protein was positive only in 3% (2/63), cathepsin D was
      expressed in 86% (48/56) and ER in 78% (25/32). Classical LC were negative for
      p53 protein and all except one were cathepsin D positive. These results are in
      contrast to invasive ductal breast carcinomas (DC), where the reported average
      incidence of vimentin and p53 protein is much higher (19% and 33% respectively)
      and that of cathepsin D and ER lower (63% and 67% respectively). Thus lack of
      expression of vimentin and lack of p53 positivity together with high incidence of
      expression of cathepsin D and ER are more often associated with lobular than with
      ductal differentiation of invasive breast cancer. The results show that LC,
      distinguished morphologically, can further be defined by its immunohistochemical
      profile. This in turn may point to underlying biological differences between LC
      and DC.

PMID- 8291223
TI  - Paraneoplastic intestinal pseudo-obstruction associated with high titres of Hu
      autoantibodies.
AB  - Anti-Hu autoantibodies in high titres, as revealed with immunocytochemistry and
      Western blot, were present in a patient with gastrointestinal pseudo-obstruction
      and small-cell lung cancer (SCLC) bearing the Hu antigen. Marked neuron and nerve
      fibre loss were found in the myenteric plexus at postmortem. These findings show
      that neuronopathic Hu-associated gastrointestinal pseudo-obstruction can occur as
      the only paraneoplastic neurological symptom in patients with SCLC.

PMID- 8291224
TI  - Primary T-cell rich B-cell lymphoma of the common bile duct.
AB  - A 34-year-old woman was hospitalized for the investigation of a one-month history
      of intestinal disorders, gastric heaviness and transitory icteric episodes.
      Extensive clinical investigations suggested the diagnosis of gall bladder
      carcinoma or sclerosing cholangitis. At laparotomy, the proximal part of common
      bile duct was markedly thickened by a white, firm, fish-flesh like tumour
      extending in to the cystic duct, gall bladder wall and to the liver. Histological
      study showed a diffuse lymphoid proliferation of the common bile duct mainly
      composed of small cells mixed with scattered large atypical cells.
      Immunohistochemistry revealed that most of the small cells expressed T-cell
      markers with predominant CD 4 and alpha-beta T-cell receptors and without
      phenotypic gap, whereas large atypical cells showed monotypic B phenotype with co
      expression of mu and delta heavy chains and light lambda chain restriction. No
      evidence of primary nodal lymphoma was found during extensive clinical,
      radiological, sonographic or scanographic examinations. Sequential chemotherapy
      (MACOP-B) was instituted and the patient was still alive 4 years after diagnosis.
      Morphological and immunohistochemistry findings fulfilled criteria for a primary
      high grade B-cell lymphoma (centroblastic type, Kiel classification) from common
      bile duct concealed by numerous small reactive T-cells, so called T-cell rich B
      cell lymphoma, not previously described in this location.

PMID- 8291225
TI  - Primary granulomatous giant cell polyphlebitis of visceral veins.
AB  - A case of granulomatous giant cell phlebitis occurred in the mesenteric veins of
      a 38-year-old man, resulting in segmental infarction of the ileum. Multiple
      epithelioid granulomas with giant cells of the Langhans type were situated in
      media/adventitia of small and middle-sized mesenteric veins with subsequent
      thrombotic venous occlusions. No involvement of arterial vessels could be
      detected. The aetiology of the disease remains unknown. Known types of vasculitis
      were excluded. It was assumed that this is an example of in immunological
      vasculopathy but this could not be proved.

PMID- 8291226
TI  - Infectious transcripts and cDNA clones of RNA viruses.

PMID- 8291227
TI  - Second-site mutations in the brome mosaic virus RNA3 intercistronic region
      partially suppress a defect in coat protein mRNA transcription.
AB  - An intercistronic oligo(A) tract is present in the genomic RNA3 of all
      bromoviruses sequenced to date and, for brome mosaic virus (BMV), is known to
      function as an activating sequence in transcription of the subgenomic coat
      protein mRNA, RNA4. Mutations able to partially compensate for removal of the
      oligo(A) from BMV RNA3 were identified by obtaining spontaneous second-site
      revertants. The starting BMV RNA3 mutant carried a deletion of 17 of 18 residues
      of the intercistronic oligo(A), resulting in a nearly complete loss of subgenomic
      coat protein mRNA synthesis and reduced RNA3 accumulation. The responsible
      suppressor mutations acted in cis and were located in the 244-base RNA3
      intercistronic region containing the original deletion. Three mutations
      associated with the revertant phenotype were characterized: (i) A single U-->A
      substitution in the core subgenomic mRNA promoter restored 35% of wild-type
      promoter activity. (ii) A duplication of 8 bases (UAUUAUUA) immediately 5' to the
      oligo(A) deletion site resulted in higher levels of both RNA3 and RNA4
      accumulation. (iii) A point substitution in a conserved cellular motif
      corresponding to box B of RNA polymerase III promoters reduced RNA3 accumulation.
      Together with certain intervirally conserved promoter sequences, the spontaneous
      adaptation of a bromovirus subgenomic promoter to function without its unusual
      oligo(A) activator suggests that bromovirus subgenomic mRNA transcription may
      share underlying mechanistic similarities with the many other members of the
      alphavirus-like superfamily, whose subgenomic promoters all lack an oligo(A)
      tract.

PMID- 8291228
TI  - Regulation of the BZLF1 promoter of Epstein-Barr virus by second messengers in
      anti-immunoglobulin-treated B cells.
AB  - Initiation of the Epstein-Barr virus (EBV) lytic cycle is dependent on the
      transcription of the BZLF1 gene. The BZLF1 gene promoter (Zp) was activated by
      crosslinking of cell surface immunoglobulin (Ig) with anti-Ig antibody in B
      cells, even in the absence of other viral genes. We identified several anti-Ig
      response elements within Zp, which were originally defined as 12-O
      tetradecanoylphorbol-13-acetate (TPA) response elements (ZI repeats and ZII, an
      AP-1-like domain). Since anti-Ig crosslinking leads to activation of protein
      kinase C (PKC) and an increase in intracellular calcium level, Zp was tested for
      the response to these cellular factors. Treatment with calcium ionophore A23187
      increased Zp activity. When the calcium ionophore was used in conjunction with
      TPA, a PKC activator, the Zp induction was synergistically enhanced. 1-(5
      Isoquinolinyl sulfonyl)-2-methylpiperazine, an inhibitor of PKC, inhibited the
      anti-Ig inducibility of Zp. Calmodulin antagonists, compound R24571 and
      trifluoperazine, blocked the Zp activation with anti-Ig. These findings suggest
      that Zp responds directly to changes in the activity of both PKC and
      calcium/calmodulin-dependent protein kinase. Requirement of tyrosine kinase
      activation for the anti-Ig-mediated Zp activation was also demonstrated through
      the use of the tyrosine kinase inhibitor herbimycin. These cellular gene
      regulatory molecules induced with anti-Ig may cooperatively play an important
      part in achieving efficient EBV activation as seen with anti-Ig treatment in B
      cells.

PMID- 8291229
TI  - Acidic pH triggers LCMV membrane fusion activity and conformational change in the
      glycoprotein spike.
AB  - Membrane fusion activity of the glycoprotein (GP) complex of LCMV was determined
      using the R18 fluorescent dequenching assay. Utilization of an endosomal entry
      route by LCMV and acidic activation of the membrane fusion activity were
      indicated by the inhibition of LCMV infection at an early stage by the lysosomal
      weak base chloroquine and the ionophore monensin. When LCMV was mixed with R18
      labeled liposomes with a lipid composition mimicking that of the endosome,
      dequenching occurred only at acidic pH (< or = 6.0). The measured dequenching was
      inhibited by protease treatment of the LCMV, indicative of protein-mediated
      membrane fusion. The initial rate of fusion was measured at pH values between 5.3
      and 7.0 and was found to decrease rapidly and linearly between pH 5.3
      (0.177%/sec) and pH 6.0 (0.027%/sec). Binding and fusion of R18-labeled LCMV with
      BHK cells were also examined. No difference was found between R18-labeled and
      unlabeled LCMV in binding to or infection of BHK cells. Dequenching was observed
      in labeled LCMV endocytosed by BHK cells. With BHK cells neither LCMV fusion with
      the plasma membrane nor LCMV-induced cell-cell fusion was observed, even under
      acidic conditions, and examination of the sequence of LCMV GP did not reveal a
      likely candidate sequence for a "fusion peptide." The binding of conformationally
      dependent monoclonal antibodies to GP was measured at neutral and acidic pH in
      order to seek evidence of pH-dependent conformational change in GP. Dissociation
      of the GP-1 from the complex was measured by sucrose gradients run on purified
      virus. These experiments revealed that after exposure to acid pH the LCMV
      glycoprotein spike complex underwent irreversible conformational change in which
      GP-1 was dissociated from the virion, conformational epitopes on GP-1 were lost,
      and sequestered epitopes on GP-2 became exposed. Further, LCMV infectivity was
      irreversibly inactivated by exposure to acidic pH (< 6.0), likely due to the loss
      of GP-1 and conformation changes in GP-2.

PMID- 8291230
TI  - Sequence analysis of the porcine epidemic diarrhea virus genome between the
      nucleocapsid and spike protein genes reveals a polymorphic ORF.
AB  - In order to investigate the genome organization of the porcine epidemic diarrhea
      virus (PEDV) further, cDNA clones covering the region between the nucleocapsid
      and the spike (S) protein genes were independently constructed and sequenced for
      the two virulent isolates Br1/87 and CV777. Of the three major ORFs identified,
      two were found to encode the major and minor coronavirus membrane proteins M and
      sM. A potentially single ORF, designated ORF3 according to the pattern of the
      viral subgenomic mRNAs, could be identified between the S and sM genes. A
      striking variability, essentially generated by short deletions clustered in a few
      loci, was observed in the ORF3 of both isolates. The largest predicted
      polypeptide of 223 amino acids showed homology with polypeptides potentially
      encoded by other members of the same genetic subset, including two shorter
      polypeptides of human respiratory virus HCV 229E and one of transmissible
      gastroenteritis virus TGEV. This homology suggests that the two HCV ORFs may have
      originated from a single precursor. The function of these polypeptides is not
      known, but the predicted products of the PEDV ORF3 and related ORFs share
      features suggestive of a membrane-associated protein.

PMID- 8291231
TI  - Complete genomes, phylogenetic relatedness, and structural proteins of six
      strains of the hepatitis B virus, four of which represent two new genotypes.
AB  - The genomes of six hepatitis B viral (HBV) strains were sequenced from 10
      overlapping amplificates obtained by the polymerase chain reaction. Four of the
      strains, specifying subtypes ayw4 and adw4q-, represented on the basis of
      divergency within the S gene two new genomic groups identified by us. The other
      two strains, encoding adrq- and of Pacific origin, belonged to genomic group C.
      The relation of these genomes to 21 published human, 1 chimpanzee, and 4 rodent
      hepadnaviral genomes was analyzed by constructing a phylogenetic dendrogram.
      Thereby, the segregation of human HBV strains into six genomic groups was
      confirmed. A consistent grouping of the genomes compared was also obtained in
      dendrograms based on the P and S genes, although the branching order differed
      from that based on the entire genomes. Each of the two representatives of genomic
      groups E and F differed by 8.1 to 13.6% and by 12.8 to 15.5% from the genomes of
      the other groups and by 1.5 and 3.7% from each other. The two Pacific group C
      strains differed by 2.7% from each other and by 4.1 to 5.4% from other group C
      genomes, suggesting that they diverged early from the other group C genomes. The
      F strains formed the most divergent group of HBV genomes, which may be explained
      by their representing the original strains of the New World. Within the
      structural gene products, 17 and 34 amino acids unique for human HBV strains were
      recorded in the sequenced E and F strains, respectively. Most notable is the
      Ser81 to Ala81 substitution in an immunodominant region of HBcAg, and the four
      extra cysteine residues in HBsAg at residues 19, 183, 206, and 220, which might
      be engaged in additional disulphide bridges. Five residues shared by E and F
      strains were also unique for human HBV strains. Two of these, Leu127 and Ser140
      in HBsAg, were the only substitutions that may explain the w4 reactivity shared
      by these HBV strains. Interestingly, the Ser140 substitution occurs in an
      immunodominant loop of the a determinant claimed to be important for the
      protective immune response to HBV vaccination.

PMID- 8291232
TI  - The vaccinia virus-encoded uracil DNA glycosylase has an essential role in viral
      DNA replication.
AB  - The vaccinia virus conditional-lethal temperature-sensitive (ts) mutant ts4149
      is, at the nonpermissive temperature, severely impaired in its ability to
      replicate its DNA genome. Compared to wild type, the amount of replication is
      suppressed by several orders of magnitude, and the little DNA that is replicated
      is not converted to mature linear genomes. We have demonstrated that this "DNA-"
      phenotype is not the result of a failure to produce early proteins. In agreement
      with the DNA- phenotype, intermediate and late gene expression were not detected.
      Marker rescue and DNA sequencing located the mutation in ts4149 to open reading
      frame D4. This gene has recently been shown to encode a 25-kDa protein with
      uracil DNA glycosylase activity (D. T. Stuart, C. Upton, M. A. Higman, E. G.
      Niles, and G. McFadden (1993), J. Virol. 67, 2503-2512). We speculate on the
      function of this "essential" viral repair enzyme and its role(s) in viral DNA
      replication.

PMID- 8291233
TI  - Cloning of Rous sarcoma virus enhancer factor genes. I. Evidence that RSV-EF-I is
      related to Y-box (inverted CCAAT) binding proteins and binds to multiple motifs
      in the RSV enhancer.
AB  - A cDNA clone was isolated from a chicken embryo cDNA library employing a PCR
      generated radiolabeled probe specific for the U3 region of the Rous sarcoma virus
      LTR. The cDNA encodes a protein of 345 aa and is homologous to the Y-box
      (inverted CCAAT) binding proteins. The amino acid sequence of the RSV-EF-I shows
      75% identity with rat EF1 but the NH2-terminal 60-aa residues share little
      homology. At the carboxyl terminus an additional 28-aa sequence, rich in basic
      residues, probably encoded by an extra exon, is present in the chicken RSV-EF-1.
      Electrophoretic mobility assays carried out with various radiolabeled
      oligonucleotides spanning the U3 region of the RSV LTR (-234 to -54) indicated
      that the RSV-EF-I binds strongly to the sequence AAGGTGGTAC and somewhat less
      efficiently to the sequences AAGGAAAG and CTTATGCAA. In contrast to rat EF1A
      which binds to the inverted CCAAT box, RSV-EF-I does not bind to the CCAAT box
      sequence. These results suggest that the RSV-EF-I, although structurally similar
      to the rat EF1A, binds differently to more than one cis-acting element. The gene
      for RSV-EF-I is expressed in a variety of cell lines, although most abundantly in
      avian fibroblasts compared to mammalian cells. It is barely expressed in normal
      lives but expressed at significantly enhanced levels in many immortalized
      hepatocytes and hepatic tumors.

PMID- 8291234
TI  - Expression of hepatitis A virus precursor protein P3 in vivo and in vitro:
      polyprotein processing of the 3CD cleavage site.
AB  - Hepatitis A virus (HAV) cDNAs encoding the P3 region proteins were expressed in
      vivo and in vitro to characterize the HAV 3D protein and to identify the cleavage
      site between 3C and 3D. Protein coding sequences were placed under control of a
      T7 promoter and an EMCV translational initiation signal. T7 RNA polymerase was
      provided by simultaneous infection of transfected BS-C-1 cells with a recombinant
      vaccinia virus vTF7-3 (T. R. Fuerst et al., Proc. Natl. Acad. Sci. USA 83, 8122
      8126, 1986). Efficient synthesis and processing of P3 proteins occurred to yield
      3CD (78 kDa), 3D (54 kDa), 3ABC (33 kDa), 3BC (25 kDa), and 3C (23 kDa). Similar
      products were produced by translation of T7 transcripts in a rabbit reticulocyte
      lysate in vitro. The 3C/D cleavage site was mapped by comparing the mobility of
      3D in SDS-PAGE with 3D proteins engineered to begin at each of the two proposed
      cleavage sites; in addition, direct N-terminal sequencing of radiolabeled 3D
      protein from translation in vitro was performed. The results showed that 3D was
      formed by cleavage at the glutamine-arginine (Q/R) pair at position 1738 and 1739
      of the HAV polyprotein. HAV 3D protein produced by autocatalytic cleavage of P3
      precursor proteins in BS-C-1 cells is virtually completely insoluble and
      sediments after low-speed centrifugation. This is in contrast to the poliovirus
      3D protein, produced from a similar construct, a significant portion of which
      remains soluble. Extracts containing the poliovirus 3D protein manifested high
      levels of RNA-dependent RNA polymerase activity, whereas those containing the HAV
      3D protein showed no detectable activity by the same assay.

PMID- 8291235
TI  - The Mastomys natalensis papillomavirus: nucleotide sequence, genome organization,
      and phylogenetic relationship of a rodent papillomavirus involved in
      tumorigenesis of cutaneous epithelia.
AB  - Mastomys natalensis is a rodent of African origin afflicted with a very high
      incidence of skin tumors (keratoacanthomas and squamous carcinomas), which are
      associated with a papillomavirus, M. natalensis papillomavirus (MnPV). We have
      determined the genomic sequence of MnPV, which has a size of 7687 bp. The genomic
      organization is similar to that of other papillomaviruses, with open reading
      frames E6, E7, E1, E2, and E4 in the early and L2 and L1 in the late region. Due
      to an unusually large hinge region, the transcriptional activator E2 has a size
      of 542 amino acids rather than 400 to 460 amino acids, as in other
      papillomaviruses. An open reading frame E5 coding for a small hydrophobic
      membrane protein is missing, as is the case for some cutaneous human
      papillomaviruses (HPV). This fact, together with the composition of cis
      responsive elements in its long control region and phylogenetic evaluation of
      segments of its E6, E1, and L1 genes, indicates a relationship of MnPV to the
      cottontail rabbit papillomavirus and several HPV types found in lesions of
      cutaneous epithelia, in particular to those that are associated with
      epidermodysplasia verruciformis. MnPV may be a useful model system for
      tumorigenesis of cutaneous epithelia in humans.

PMID- 8291236
TI  - Molecular characterization of border disease virus, a pestivirus from sheep.
AB  - Three serologically different pestivirus strains isolated from sheep were
      selected for molecular analysis. cDNA and deduced amino acid sequences of the
      genomic regions encoding glycoproteins E1 and E2 were obtained from the three
      strains. A comparison with amino acid sequences of bovine viral diarrhea virus
      (BVDV) and classical swine fever virus (CSFV) revealed that one of the three
      ovine pestivirus strains can be grouped together with BVDV. The other two
      strains, however, were clearly different from both BVDV and CSFV. Surprisingly,
      the amino acid sequences from these two viruses were more similar to CSFV than to
      BVDV. The identity between so-called "true" BDV strains at the amino acid level
      is about 95% for E1 and 86% for E2 and thus similar to homologies found between
      CSFV strains. For one "true" BDV strain the genomic region encompassing the
      nonstructural protein p125 was also cloned and sequenced. The respective
      comparative analysis led to results which are similar to the ones obtained for
      the two structural glycoproteins. Taken together the data demonstrate that "true"
      border disease virus strains represent a separate group within the genus
      pestivirus.

PMID- 8291237
TI  - Identification of a short viral transcript in Leishmania RNA virus-infected
      cells.
AB  - Certain strains of Leishmania guyanensis carry persistently infecting double
      stranded RNA viruses. The viral polymerase has been shown to have both
      transcriptase and replicase activity. To date, only full-length RNA transcription
      of minus and plus strands have been reported. This report describes the synthesis
      of a 320 nt transcript which is complementary to the 3' end of the minus strand
      RNA. This plus-stranded short transcript was first detected in an in vitro
      polymerase assay. It was also detected in virus-infected Leishmania cells by a
      reverse transcription-polymerase chain reaction assay and by Northern analysis of
      infected Leishmania cell RNA.

PMID- 8291238
TI  - Analysis of the influenza virus gene pool of avian species from southern China.
AB  - Although Southern China has been considered the epicenter of human influenza
      pandemics, little is known about the genetic composition of influenza viruses in
      lower mammals or birds in that region. To provide information on the molecular
      epidemiology of these viruses, we used dot blot hybridization and phylogenetic
      methods to study the internal genes (PB1, PB2, PA, NP, M, and NS) of 106 avian
      influenza A viruses isolated from a total of 11,798 domestic ducks, chickens, and
      geese raised in Southern China including Hong Kong. All 636 genes examined were
      characteristic of avian influenza viruses; no human or swine influenza genes were
      detected. Thus, influenza virus reassortants do not appear to be maintained in
      the domesticated birds of Southeast Asia, eliminating opportunities for further
      gene reassortment. Phylogenetic analysis showed that the internal genes of these
      viruses belong to the Eurasian avian lineage, supporting geographical separation
      of the major avian lineages. The PB1 genes were most similar to A/Singapore/57
      (H2N2) and Hong Kong (H3N2) viral genes, supporting an avian origin for the
      recent human H2N2 and H3N2 pandemic strains. The majority of internal genes from
      avian influenza viruses in Southern China belong to the Eurasian lineage and are
      similar to viruses that have recently been transmitted to humans, swine, and
      horses. This study provides evidence that the transmission of avian influenza
      viruses and their genes to other species is unidirectional and that the
      transmission of mammalian influenza virus strains to domestic poultry is probably
      not a factor in the generation of new pandemic strains.

PMID- 8291239
TI  - The carboxyl-half of the rotavirus nonstructural protein NS53 (NSP1) is not
      required for virus replication.
AB  - The rotavirus nonstructural protein NS53 (NSVP1), the product of genome segment
      5, possesses RNA-binding activity and contains a highly conserved cysteine-rich
      motif located in the amino-terminal half of the protein. The genome of the bovine
      rotavirus variant, brvA, lacks a normal segment 5 but includes a novel dsRNA
      (gene A) of approximately 2600 basepairs (bp) that contains segment 5-specific
      sequences (F. Hundley, B. Biryahwaho, M. Gow, and U. Desselberger, Virology 143,
      88-103, 1985). To gain information about the nature of the rearrangement in gene
      A and its capacity to encode a protein product, we prepared and sequenced
      complementary (c)DNA of the gene A RNA. The results showed that gene A is 2693 bp
      in size and contains a head-to-tail duplication of 1112 bp that originates from
      the open reading frame (ORF) of gene 5. The duplication begins at nucleotide (nt)
      1454, which is 53 nt upstream from the end of the ORF for NS53. Gene A contains a
      point mutation at nt 808 which results in the presence of a nonsense codon near
      the middle of the ORF for NS53. Thus the predicted product of gene A is a
      truncated NS53 of 258 amino acids (aa) (31 kDa), approximately one-half the size
      of the authentic 491-aa NS53 (58 kDa). Examination of lysates from brvA-infected
      cells by Western blot assay using an NS53-specific antibody confirmed that the
      variant encodes only a truncated gene 5 product. Despite the truncation, analysis
      of the gene A product suggested that it, like full-length NS53, accumulated in
      association with the cytoskeleton of the infected cell, thus providing evidence
      that the subcellular localization signal in NS53 resides in the amino terminal
      half of the protein. Given that brvA is a viable, nondefective mutant, these
      results demonstrate that the carboxyl-terminal 233 aa of NS53 are not required
      for rotavirus replication in vitro.

PMID- 8291240
TI  - Efficient foreign gene expression in Epstein-Barr virus-transformed human B
      cells.
AB  - Epstein-Barr virus (EBV) is a herpesvirus that transforms B-cells (B-LCL) and has
      undergone intense scrutiny owing to its association with Burkitt's lymphoma,
      nasopharyngeal carcinoma, and immunoblastic lymphomas. B-LCL have also proven
      useful in the study of human immunology. We describe a novel system for inducing
      efficient foreign gene expression in B-LCL using biotinylated adenovirus as an
      endosome-disrupting agent. Plasmid DNA is coupled to the exterior of viral
      particles by streptavidin-polylysine chimeric proteins. Up to 67% of B-LCL may be
      induced to express foreign genes in vitro in transient expression systems, and
      gene expression lasts for at least 17 days. We have expressed firefly luciferase,
      beta-galactosidase (beta-gal), chloramphenicol acetyltransferase, HIV gag, and
      env genes, as well as infectious HIV, and the EBV-specific BZLF gene in B-LCL
      with this system. In vivo delivery of a beta-gal reporter gene to B-LCL was
      documented in a SCID mouse model. Potential applications include study of genetic
      regulation of EBV infection and transformation events, study of potential gene
      therapies for EBV-related B-cell tumors, and production of antigen-presenting
      cells for use in immunologic assays. Because of the high percentage of cells
      transformed and the length of foreign gene expression, the possibility of
      examining foreign gene expression in transient assays, without selection for
      clonal populations, exists.

PMID- 8291241
TI  - Expression of the rubella virus nonstructural protein ORF and demonstration of
      proteolytic processing.
AB  - To analyze the proteins produced from the rubella virus (RUB) nonstructural
      protein open reading frame (NSP-ORF), a DNA containing the RUB NSP-ORF was
      introduced into the expression vector pTM3 in which the sequences to be expressed
      are downstream from a T7 RNA polymerase promoter. In cells infected with a
      vaccinia virus recombinant which expresses T7 RNA polymerase and transfected with
      this plasmid, three RUB-specific products with electrophoretic mobilities of 200,
      150, and 97 kDa were clearly visible. By computer alignment, the presence of a
      cysteine protease was predicted within the NSP-ORF (A. E. Gorbalenya et al., FEBS
      Lett. 288, 201-205, 1991). When the Cys proposed as the catalytic residue of this
      protease (Cys1151) was mutated to a Gly, only the 200-kDa product was produced,
      demonstrating that the Cys is important in the activity of the protease
      responsible for the processing of the RUB NSPs and that the 150- and 97-kDa
      species are processing products. Transfections with deletion mutants revealed
      that the 150-kDa processing product is derived from the amino-terminal two-thirds
      of the ORF and that both the protease and the cleavage site on the COOH-terminal
      side of the 150-kDa product are between amino acids 1005 and 1507 of the ORF.

PMID- 8291242
TI  - New overlapping gene encoded by the cucumber mosaic virus genome.
AB  - Cucumber mosaic virus (CMV) contains three genomic RNAs (RNAs 1, 2, and 3) and a
      subgenomic RNA (RNA 4), a shared feature of the Bromoviridae family which
      includes cucumoviruses, bromoviruses, alfalfa mosaic virus, and ilarviruses. We
      describe in this paper the molecular characterization of a novel subgenomic RNA
      of the Q strain of CMV (Q-CMV), RNA 4A, which was first reported in 1973 (K. W.
      C. Peden and R. H. Symons, Virology 53, 487-492, 1973). RNA 4A is 682 nucleotides
      and is identical in sequence to the 3'-terminal 682 nucleotides of RNA 2. RNA 4A
      encodes a small open reading frame (ORF) of 100 codons, which, in RNA 2, overlaps
      the C-terminal portion of the major 2a gene; thus it is likely that RNA 4A
      functions as the mRNA for the in vivo expression of the ORF, called ORF 2b.
      Polyclonal antibodies raised against a 2b fusion protein expressed in Escherichia
      coli specifically detected the 2b gene product in Q-CMV-infected cucumber plants
      by Western immunoblotting. Examination of published viral RNA sequences revealed
      the conservation of ORF 2b in all of the four other cucumoviruses sequenced to
      date; however, it is absent from the rest of the Bromoviridae. We suggest that
      the proposed ORF 2b may be expressed in other cucumoviruses, most likely via 4A
      like subgenomic RNAs, and that the predicted gene product may have a unique
      functional role in the infection process of cucumoviruses.

PMID- 8291243
TI  - The polymerase-associated protein (M1) and the matrix protein (M2) from a
      virulent and an avirulent strain of viral hemorrhagic septicemia virus (VHSV), a
      fish rhabdovirus.
AB  - We have cloned and sequenced the M1 and M2 genes of both a European (virulent)
      and a North American (avirulent) strains of viral hemorrhagic septicemia virus,
      an important fish pathogen. We also compared the transcription of the two genes
      following infection of cells and determined the phosphorylation status and
      detergent solubility of the two proteins. Despite a total lack of homology with
      any available rhabdoviral sequence, the two VHSV proteins share comparable
      structural features with their respective VSV and RV equivalents. Thus, they are
      likely to exert similar functions. The amino acid sequence of both proteins is
      highly conserved between the European and the North American strains, indicating
      a probable common origin. The most remarkable features are that the virulent and
      avirulent strains differ in the location of the transcription start signal for
      the M2 gene and in TX-114 detergent solubility of the M2 protein. However, these
      differences are not paralleled with any observable change at the levels of M2
      gene transcription, M2 protein expression, or virion maturation. Thus, they are
      unlikely to play a significant role in determination of the virulent status.

PMID- 8291244
TI  - Immunolocalization of vaccinia virus structural proteins during virion formation.
AB  - Proteolytic processing of vaccinia virus core proteins is an essential step in
      the formation of mature virions and occurs during the process of virion
      morphogenesis. In order to investigate how the vaccinia virus (VV) structural
      proteins become integrated into virus particles during normal maturation,
      immunological reagents were generated against the three major VV core proteins
      4a, 4b, and 25K and their precursor molecules P4a, P4b, and P25K. These sera were
      used in conjunction with immunofluorescent and immunogold labeling of VV-infected
      tissue culture cells. The immunofluorescent results indicated that all three core
      precursors and their cleavage products were localized to virosomes. As the
      infection progressed, punctate staining with these sera became spread throughout
      the cytoplasm which suggested that individual virion particles were being
      recognized. Immunoelectron microscopy showed that the core proteins were
      localized to the center of both immature and mature virus particles. This result
      was in contrast to the situation observed using antisera directed against L65, a
      protein previously implicated in the assembly of the viral membrane. Immunogold
      staining of L65 showed that it was initially located along the inner side of the
      immature virion membrane and remained with the membrane even as the viroplasm
      began to condense toward the center of the virus particle. In order to determine
      whether the core protein localization observed was the result of precursors,
      products, or both, a synthetic peptide strategy was used to generate an antiserum
      that recognized only P4a in immunoprecipitation reactions. Immunogold labeling
      with this reagent indicated that P4a was found in the viroplasm of immature
      particles and in low levels in the mature virion. Intracellular localization of
      core and L65 proteins during virion morphogenesis is discussed.

PMID- 8291245
TI  - Production of nonstructural proteins of hepatitis C virus requires a putative
      viral protease encoded by NS3.
AB  - Hepatitis C virus (HCV) is a positive strand RNA virus with certain similarity to
      flaviviruses and pestiviruses. To examine the processing and possible assembly of
      HCV proteins, we constructed a recombinant vaccinia virus that expresses a full
      length genomic RNA, infected chimp liver cells with the virus, and analyzed HCV
      related protein products by immunofluorescent antibody staining and Western blot
      detection with mouse monoclonal antibodies. The putative core, envelope, and NS1
      and NS3 proteins that yielded from this recombinant were 22, 32, 53 to 58, and 65
      kDa in size, respectively. The NS4 protein was unexpectedly small, with an
      estimated molecular weight of 7 kDa, and the NS5 protein was found to be further
      cleaved into 52-kDa NS5a and 58-kDa NS5b proteins, the latter of which contains a
      hallmark of RNA replicase. A point mutation in the putative protease domain of
      NS3 resulted in a failure in the production of NS3, NS4, NS5a, and NS5b, but
      coexpression of NS3 restored the proper processing of these proteins,
      demonstrating that NS3, the putative viral protease, is essential for the
      production of these nonstructural proteins. Thus, HCV strikingly resembles
      pestiviruses in the size and the processing mode of the nonstructural proteins,
      particularly NS4 and NS5.

PMID- 8291246
TI  - Genome characterization and identification of viral-associated dsDNA component of
      banana bunchy top virus.
AB  - The single-stranded (ss) and double-stranded (ds) viral-associated DNAs (VADs) of
      banana bunchy top virus (BBTV) were characterized. The ssVADs were shown to be
      the viral genomic DNA and the dsVADs are the likely replication forms. Both
      dsVADs and ssVADs contain DNA species that cross-hybridize to each other. Under
      the electron microscope, both circular and linear DNAs were observed from these
      VAD species. Libraries were constructed from VADs to further characterize them.
      Two overlapping VAD clones were isolated and their combined sequence indicated
      that their corresponding VAD, named as BBTV component 2, is circular with a size
      of 1095 nt. The largest ORF spans from nucleotides 82 to 390, which is sandwiched
      by a putative TATA box, 54 nt upstream from the first ATG codon, and a AATAAA
      motif, 7 nt downstream from the UAA codon. Although the sequence of this VAD is
      different from the previously reported BBTV component 1 (Harding et al., J. Gen.
      Virol. 74, 323-328, 1993) and the genome of coconut foliar decay virus (Rohde et
      al., Virology 176, 648-651, 1990), stretches of highly homologous sequences were
      found between BBTV component 2 and the other two viral genomes by computer
      analysis. The sequence of BBTV component 1 is highly homologous to one of the
      clones, pBTs26, in the VAD library. Nevertheless, our libraries still contain
      many clones which hybridized with ss viral genomic DNAs but not with pBTs26 and
      BBTV component 2, indicating that the viral genome consists of more than two
      components.

PMID- 8291247
TI  - Splicing in a plant pararetrovirus.
AB  - Analysis of expression in rice cells of plasmids in which an ATG-less
      chloramphenicol acetyl transferase ORF was placed in frame with the coding
      sequence of the pararetrovirus rice tungro bacilliform virus (RTBV) ORF IV, and
      which contained much of the upstream full-length transcript sequence of RTBV,
      gave evidence to suggest that a splicing event occurred. Reverse
      transcription/PCR of RNA from transfected protoplasts and from RTBV-infected
      plants yielded a product which confirmed that the 5' end of ORF IV was spliced in
      frame to a short ORF (sORF) in the RTBV leader sequence removing an intron of
      about 6.3 kb. Most of the translation is initiated at the ATG codon in the sORF
      with only about 10% at the ORF IV ATG codon. The efficiency of splicing appears
      to be inversely related to the length of the intron. The finding of splicing in a
      pararetrovirus blurs the differences between them and retroviruses but is in
      accord with the hypothesis that retroelements acquire genes and sequences which
      adapt them to specific niches.

PMID- 8291248
TI  - Soybean dwarf luteovirus contains the third variant genome type in the luteovirus
      group.
AB  - Complementary DNAs covering the entire RNA genome of soybean dwarf luteovirus
      (SDV) were cloned and sequenced. Computer analysis of the 5861 nucleotide
      sequence revealed five major open reading frames (ORFs) possessing conservation
      of sequence and organisation with known luteovirus sequences. Comparative
      analyses of the genome structure show that SDV shares sequence homology and
      features of gene organisation with barley yellow dwarf virus (PAV isolate) in the
      5' half of the genome, yet is more closely related to potato leafroll virus in
      its 3' coding regions. In addition, SDV differs from other known luteoviruses in
      possessing an exceptionally long 3' terminal sequence with no apparent coding
      capacity. We conclude from these data that the SDV genome represents a third
      variant genome type in the luteovirus group.

PMID- 8291249
TI  - Functional mapping of regions of the Autographa californica nuclear polyhedrosis
      viral genome required for DNA replication.
AB  - Previous results showed that plasmids containing one of the eight putative
      origins (ori's) of Autographa californica nuclear polyhedrosis virus (AcMNPV) are
      replicated after transfection into Spodoptera frugiperda cells if essential trans
      acting factors are supplied by AcMNPV infection (Kool et al., Virology, 192, 94
      101, 1993a; Kool et al., J. Gen. Virol., in press, 1993b; Leisy and Rohrmann,
      Virology, 196, 722-730, 1993). In this report a transient complementation assay
      is described in which four cotransfected cosmid clones, instead of AcMNPV
      infection, provided essential trans-acting factors for plasmid DNA replication.
      In this assay plasmid replication was found to be independent of the presence, in
      cis, of a viral ori. No replication of plasmids occurred when one of the cosmids
      was omitted from the transfection mixture. This result indicated that this assay
      is a valid approach for identification of AcMNPV replication genes. We further
      used the assay to define essential regions in the four required cosmids. Six
      regions of the AcMNPV genome, EcoRI-I (map unit 0.3-5.8), EcoRI-O (map unit 6.9
      8.7), SstI-F (map unit 38.9-45.0), EcoRI-D (map unit 59.9-68.3), a BamHI-SstII
      fragment of BamHI-B (map unit 84.3-89.7), and EcoRI-B (map unit 90.0-100), with
      at least seven genes, were found to be essential for plasmid DNA replication.
      These regions contain the putative DNA polymerase gene (SstI-F), the helicase
      like gene (EcoRI-D), and the region where most of the trans-activating immediate-
      early genes of AcMNPV are located (EcoRI-B). For SstI-F it was shown that this
      region contains besides the DNA polymerase gene at least one other replication
      gene. These results show that it will now be possible to define the set of AcMNPV
      genes necessary and sufficient for DNA replication.

PMID- 8291250
TI  - Cell-specific kinetics and efficiency of herpes simplex virus type 1 entry are
      determined by two distinct phases of attachment.
AB  - We previously provided evidence for a model of herpes simplex virus type 1 (HSV
      1) entry by a cascade of interactions between components of the virion envelope
      and cellular plasma membrane (Fuller and Lee, 1992, J. Virol. 66, 5002-5012). In
      this report we have determined entry kinetics of wild-type HSV-1 into two highly
      susceptible cell lines to further explore the contributions of viral or cellular
      factors to entry. Penetration rates of preattached virus varied among several
      common laboratory HSV-1 strains into one cell line. However, entry kinetics
      varied substantially for a single strain into highly susceptible HEp-2 or Vero
      cells under identical conditions. Plaquing efficiencies and sensitivity to
      heparin also significantly differed between these cells. Kinetics of entry that
      included virus attachment and penetration showed that the cell-specific effects
      can be explained by two distinct phases of attachment that occurred before
      penetration, but differed in duration on both susceptible cell lines. Initial
      attachment of virus is resistant to removal with phosphate-buffered saline, but
      sensitive to removal with buffer containing heparin. This is followed by a second
      type of attachment that is heparin resistant, but still sensitive to
      extracellular inactivation. We conclude that although undefined factors unique to
      individual wild-type HSV-1 laboratory strains affect entry kinetics, entry of any
      one strain is greatly influenced by interactions of virus with specific cell
      components during at least two distinct phases of attachment before penetration.
      Moreover, the second phase to stabilize binding seems to be the rate-limiting
      event in entry. Since major differences in the amounts or sulfation patterns of
      heparan sulfate were not detected, differences in the surfaces of HEp-2 and Vero
      cells that influence the kinetics and efficiency of HSV-1 entry are likely in the
      fine structure of heparan sulfate or in the presence and quantity of other
      unidentified receptors.

PMID- 8291251
TI  - Adenovirus type 12 early region 1A expresses a 52R protein repressing the trans
      activating activity of transcription factor c-Jun/AP-1.
AB  - Oncoproteins of the early transcription unit 1A (E1A) of adenoviruses (Ad) are
      known to modulate the expression of all viral and of a variety of cellular genes.
      In this communication we present data demonstrating for the first time an
      activity associated with a protein (the 52R protein) expressed exclusively from
      E1A of the highly oncogenic subtype Ad12. The 52R protein, which does not contain
      any of the conserved regions (CR1-CR3) necessary for the trans-regulatory
      functions of the larger E1A proteins (266R, 235R), represses the trans-activating
      activity of the transcription factor c-Jun/AP-1. The repression of c-Jun/AP-1
      activity is neither due to a down-regulation of the c-jun transcription rate nor
      due to an inhibition of binding of the transcription factor complex to its target
      sequence, at least under the conditions of in vitro band shift assays. As the 52R
      protein is most probably not associated with DNA-bound c-Jun/AP-1, we suppose
      that it represses c-Jun activity either by a squelching mechanism sequestering a
      cofactor, which is an essential link between c-Jun/AP-1 and the components of the
      basal transcriptional machinery or by modifying post-translational modifications
      necessary for the trans-activation function of c-Jun.

PMID- 8291252
TI  - Evolution of the nucleoprotein and matrix genes of wild-type strains of measles
      virus isolated from recent epidemics.
AB  - To characterize the genetic properties of currently circulating strains of wild
      type measles viruses, we constructed and sequenced cDNA clones of the
      nucleoprotein (N) and matrix (M) genes of wild-type strains isolated between 1958
      and 1989. The N and M genes of wild-type isolates from the prevaccine era (before
      1964) were highly related to each other and to the N and M genes of a currently
      used measles vaccine strain, Moraten. The N and M genes of these viruses differed
      by no more than 0.5% at the nucleotide level. In contrast, the N and M genes of
      wild-type viruses isolated between 1977 and 1989 showed genetic drift, with the
      greatest amount of drift occurring in the viruses isolated from recent cases in
      the United States. Overall, the M genes were slightly more conserved at the
      nucleotide level (2.6% nucleotide, 3.3% amino acid) than the N genes (4.8%
      nucleotide, 3.4% amino acid). Alignment of the predicted protein sequences of the
      N genes revealed two regions of amino acid heterogeneity. The evolutionary
      patterns for the N and M genes suggested that the wild-type viruses isolated in
      the United States in 1989 were more related to wild-type viruses isolated in the
      United Kingdom between 1983 and 1988 than to viruses isolated in the United
      States in 1983.

PMID- 8291253
TI  - Interferon-gamma severely inhibits DNA synthesis of vaccinia virus in a
      macrophage cell line.
AB  - Interferon-gamma inhibits the growth of several viruses; however, the exact
      mechanism of this inhibition has not been clearly defined. In this report, we
      show that in a monocyte/macrophage cell line J774.G8 IFN-gamma inhibits the
      growth of vaccinia virus (VV) in a dose-dependent manner. This inhibition is due
      to a block in VV DNA synthesis and correlates with an increased generation of
      reactive nitrogen intermediates.

PMID- 8291254
TI  - Mouse hepatitis virus strain A59 RNA polymerase gene ORF 1a: heterogeneity among
      MHV strains.
AB  - Gene 1, the putative RNA replicase gene of coronaviruses, is expressed via two
      large overlapping open reading frames (ORF 1a and ORF 1b). We have determined the
      nucleotide sequence of ORF 1a, encoded within the first 13.7 kb of gene 1, for
      the coronavirus mouse hepatitis virus strain A59 (MHV-A59). Putative papain-like
      protease domains, a picornavirus 3C-like protease domain, two hydrophobic
      domains, and a domain "X" of unknown function, previously identified in other
      coronaviruses (1-3), are also present in ORF 1a of MHV-A59. Comparison between
      the ORF 1a sequence of MHV-A59 and the published sequence of the JHM strain of
      MHV (2) showed a high degree of similarity with the exception of several short
      regions. We sequenced one region of MHV-JHM that contained an 18 amino acid
      insertion relative to A59 and four other regions in which the sequences of the
      two strains differed. The MHV-2 and MHV-3 strains were also sequenced in some of
      these regions. Our analysis confirmed the presence of only one heterogeneous
      region in ORF 1a of MHV-A59 and MHV-JHM which is also present in MHV-2. Our
      findings indicate the need to modify the published sequence of MHV-JHM.

PMID- 8291255
TI  - 2A proteinases of coxsackie- and rhinovirus cleave peptides derived from eIF-4
      gamma via a common recognition motif.
AB  - The cleavage specificities of the 2A proteinases from coxsackievirus B4 (CVB4)
      and human rhinovirus 2 (HRV2) on oligopeptide substrates have been determined.
      Comparison of the specificity of CVB4 2A proteinase with that of HRV2 2A
      proteinase allowed cleavable peptides to be designed using the common motif
      IIe/Leu-X-Thr-X*Gly; little resemblance to the viral cleavage site remained. The
      data also allowed the prediction of three possible cleavage sites for 2A
      proteinases on eIF-4 gamma; two peptides derived from these sequences were
      cleaved by both 2A proteinases. One of these peptides corresponds to the cleavage
      site for 2A proteinases mapped on eIF-4 gamma [B. J. Lamphear et al. (1993) J.
      Biol. Chem. 268, 19200-19203]. This supports the hypothesis that cleavage of eIF
      4 gamma by picornaviral 2A proteinases occurs directly.

PMID- 8291256
TI  - [Epidemiology and diagnosis of allergic diseases].
AB  - Epidemiological studies indicate a world-wide and significant increase in atopic
      diseases over the past decades, which has adopted alarming dimensions within the
      industrialized world. However, allergic asthma and pollinosis, in particular, are
      on the increase in Third world countries, in parallel to the industrialization
      and westernization of their life-style. Since both antigen exposure and the
      presence of additional realization factors are required for the manifestation of
      atopic diseases, this increase in prevalence is not surprising. In addition to
      increased indoor and outdoor pollution, changes in the way of living--causing
      increased allergen exposure--certainly play an important role as cofactor in the
      increased incidence of allergies. Accurate diagnostic procedures permit a better
      understanding of the realization factors for allergic diseases in epidemiological
      studies and identification of the causative agent in the individual so that
      effective therapeutic and prophylactic steps can be taken. Despite improved in
      vivo and in vitro test methods, the case history is still of paramount importance
      in reaching a diagnosis; the potential hazards of skin and provocation testing,
      as well as the high costs and limitations of in vitro methods prohibit "blind
      allergy screening".

PMID- 8291257
TI  - [Drug allergies].
AB  - Drug allergies can be classified into three subgroups which differ in their
      pathophysiology and require different diagnostic steps: 1. classical drug
      allergies, which are directed against the drug itself, a reactive metabolite or
      some contaminant of the drug, 2. pseudoallergic reactions, which are caused by
      non-immune mediated degranulation of mast cells and basophils, and 3. autoimmune
      reactions, in which the drug elicits an immune reaction to autologous structures.
      A very detailed accurate history is of the greatest importance in the
      clarification of a suspected drug allergic reaction, as well as experience with
      the drug. In addition, skin tests, serological tests and the lymphocyte
      transformation test may be useful. One should differentiate between tests which
      imitate the drug-elicited allergic reaction (i.e., Coombs test in drug-induced
      hemolytic anemia) and tests which solely indicate a sensitization and the tests
      must be interpreted accordingly.

PMID- 8291258
TI  - [Contact allergy].
AB  - Following epicutaneous application of a potential contact sensitizing agent
      (hapten) allergic contact dermatitis results if sensitizing rather than
      tolerizing signals become dominant. Whereas downregulatory signals are poorly
      defined it has become clear that epidermal Langerhans cells play an important
      role in the induction of contact allergy. The current hypothesis is that in vivo,
      subsequent to deposition of antigen, resident Langerhans cells mature into potent
      immunostimulatory, antigen-carrying dendritic cells which migrate via the
      afferent lymphatics and after their arrival in the draining lymph node select and
      sensitize clones of antigen-specific T-cells from the circulating pool. These T
      cells produce Interleukin-2 and Interferon-gamma, and, thus, constitute so-called
      type 1 helper T-cells (Th 1). Recent progress has shed light on some major
      unknowns in this sequence of events such as regulatory influences, nature of the
      T-cell receptor ligand, and extravasation of T-cells at the site of hapten
      deposition. For example, epidermal cell-derived cytokines seem important for
      initiation (Interleukin-1) and sustenance (GM-CSF) of the induction phase. Hapten
      specific T-cells seem to see hapten molecules bound to peptides in the groove of
      the MHC molecules, and specific endothelial adhesion molecules (ELAM-1) mediate
      extravasation of skin-homing T-cells that carry a specific ligand (CLA). The
      recent development of techniques to grow murine as well as human Langerhans cells
      and dendritic cells in large numbers will allow researchers to further elucidate
      the pathogenesis of contact hypersensitivity and will ultimately lead to the
      design of novel strategies for immodulation and tolerance induction.

PMID- 8291259
TI  - [Allergic diseases in childhood].
AB  - Natural exposure to allergens initiates an allergic inflammatory response in
      genetically disposed individuals. Allergic symptoms are associated with
      mucocutaneous sensitivity and production of allergen-specific IgE antibodies.
      Infections, environmental irritants and emotional factors also influence the
      clinical manifestation of allergic disease in childhood. Therefore mechanisms of
      specific and non-specific sensitivity must be considered and treated. For
      diagnostic purposes we have to prove the dose-related response to allergen
      exposure, as well as the participation of IgE-mediated disease. The patient's
      history, skin prick test and measurement of specific IgE in serum are reliable
      parameters. Successful treatment consists of avoidance to allergens, symptomatic
      medication to reduce the allergic inflammation and specific allergen
      immunotherapy. The use of hypoallergenic formulae in infancy have still to be
      investigated for their long-acting prophylactic efficacy.

PMID- 8291260
TI  - Hepatic microsomal metabolism of the potential memory-enhancing agent, CL
      275,838, to its desbenzyl derivative.
AB  - 1. The oxidation of the potential memory-enhancer and antidepressant agent CL
      275,838 by rat liver microsomes was investigated. CL 275,838 was rapidly and
      extensively biotransformed in vitro to its desbenzyl derivative (II), the main
      metabolite observed in vivo. No other known metabolites could be detected in the
      incubation mixture except for trace amounts of a hydrolysis product (IV). 2. The
      formation of the desbenzylated derivative II required the presence of an NADPH
      generating system and was significantly inhibited by carbon monoxide, SKF 525-A
      and cimetidine, indicating the participation of P450 in the oxidation of CL
      275,838. The reaction was markedly enhanced by phenobarbital and by pregnenolone
      16 alpha-carbonitrile [particularly in the female]. beta-Naphthoflavone did not
      significantly affect desbenzylation. 3. Kinetic studies indicate that there are
      sex-dependent differences in CL 275,838 metabolism in vitro, as observed in vivo
      in rat. Maximal velocity for the oxidation of CL 275,838 in microsomes isolated
      from the male rat was 17 times greater than in the female rat. The apparent Km
      for metabolism of CL 275,838 was similar in microsomes derived from the male and
      female rat. 4. CL 275,838 does not appreciably affect its own oxidation and does
      not cause significant hepatic microsomal enzyme induction in the male or female
      rat, except for slight enhancement of some components of the P450 system at doses
      (300 mg/kg once daily for 7 days) well above the effective pharmacological range.

PMID- 8291261
TI  - Distribution and elimination of the herbicide propanil in the channel catfish
      (Ictalurus punctatus).
AB  - 1. The uptake, elimination and tissue distribution of total radioactivity derived
      from the herbicide, [14C]propanil (3,4-dichloropropionanilide) and its
      metabolites were examined in individual farm-raised Channel Catfish which were
      exposed for 24 h to water containing 1 ppm of 14C-propanil under static
      conditions. Uptake and elimination of total radioactivity was monitored in
      individual animals over time in respective exposure (24 h) and depurating (144 h)
      aquaria. 2. Maximal uptake was reached between 8 and 12 h with approx. 38% of the
      absorbed radioactivity remaining in the animal after 144 h of depuration. Whole
      body depuration of radioactivity was biphasic with alpha and beta half-lives of
      20 and 444 h, respectively. 3. Tissue distribution of total radioactivity was
      monitored at various time points in 12 tissues and bile over 48 h. Intestine,
      abdominal fat and liver possessed the greatest levels of radioactivity per gram
      of tissue over time. Radiolabel was shown to slowly increase in bile and
      intestine indicating biliary excretion as a possible pathway of metabolite
      elimination. 4. Bile possessed approx. 104 nmol (23%) of the remaining
      radioactivity in fish after 48 h. Other whole tissues possessing > 10% of
      radiolabel after 48 h were blood (83.5 nmol, 19% of the administered dose) and
      muscle (190 nmol, 43%).

PMID- 8291262
TI  - Identification of goat and mouse urinary metabolites of the pneumotoxin, 3
      methylindole.
AB  - 1. Urine from goats dosed i.v. with 3-methylindole (3MI; 15 mg/kg) or [methyl
      14C] 3MI (15 mg/kg, 0.5 microCi/kg) contained at least 11 metabolites of 3MI. 2.
      Goat metabolized 3MI to sulfate conjugates of 4- or 7-hydroxy-3-methyloxindole, 5
      or 6-hydroxy-3-methyloxindole, and 3,5- or 6-dihydroxy-3-methyloxindole;
      glucuronic acid conjugates of indole-3-carboxylic acid and 4- or 7-hydroxy-3
      methyloxindole; and unconjugated 3-hydroxy-3-methyloxindole. Diastereoisomeric
      glucuronic acid conjugates of 3-hydroxy-3-methyloxindole were also identified in
      goat urine. 3. Urine from mice dosed i.p. with 3MI (400 mg/kg) or [ring-UL-14C]
      3MI (400 mg/kg, 125 microCi/kg) contained at least six metabolites of 3MI. 4.
      Mice metabolized 3MI to glucuronic acid conjugates of 3,5- or 6-dihydroxy-3
      methyloxindole, 5- or 6-hydroxy-3-methyloxindole, and indole-3-carboxylic acid;
      and unconjugated indole-3-carboxylic acid. Unconjugated 3-hydroxy-3
      methyloxindole was identified in mouse urine in a previous report. 5. Both goats
      and mice metabolized 3MI to a mercapturate, 3-[(N-acetyl-L-cystine-S
      yl)methyl]indole, which has been previously identified and was confirmed in this
      study. 6. 3-Methyloxindole was not identified in the urine of either goats or
      mice. 7. The major pathways of 3MI biotransformation in goats and mice is the
      formation of mono- and dihydroxy-3-methyloxindoles and their subsequent
      conjugation with glucuronic acid or sulfate. 8. There are no apparent qualitative
      differences in the biotransformation of 3MI between goats and mice that can
      account for their different sensitivities to 3MI-induced lung injury.

PMID- 8291263
TI  - N-acetyltransferase activity in rainbow trout liver and in vitro
      biotransformation of chlorinated anilines and benzenes in fish.
AB  - 1. N-acetyl transferase activity in liver homogenate of rainbow trout
      (Oncorhynchus mykiss) was studied. Enzyme activity depends on the concentration
      of cofactor, has a broad pH and temperature optimum, is not linear with protein
      concentration within the whole range tested, and does not decrease upon storage
      at -70 degrees C. 2. In vitro biotransformation of several chlorinated anilines
      and benzenes was studied in liver homogenates of rainbow trout and swordtail
      (Xiphophorus helleri). Several phase I and II products were detected in the
      simple in vitro biotransformation assays using different cofactors NADPH
      regenerating system and acetyl-CoA, respectively. Acetylation of di-ortho
      substituted anilines was not observed. 3. Apparent Vmax and Km values for the
      acetylation of trichloroanilines have been determined using rainbow trout liver
      homogenate. The rate or extent of N-acetylation is related to the structure and
      properties of the chlorinated anilines. 4. Comparison of the data for the two
      species showed that there are no apparent qualitative differences in the in vitro
      fate of the chlorinated anilines and benzenes studied. It is concluded that
      results obtained for these chemicals in the in vitro biotransformation assay can
      be extrapolated between the taxonomic families of Salmonidae and Poeciliidae. 5.
      The in vitro and in vivo N-acetylation of the chlorinated anilines turned out to
      be strikingly similar. Therefore, simple in vitro systems may be of use in
      assessing the potential of chemicals to bioconcentrate.

PMID- 8291264
TI  - Pharmacokinetics, bioavailability, plasma protein binding and disposition of
      nalidixic acid in rainbow trout (Oncorhynchus mykiss).
AB  - 1. The pharmacokinetics, disposition and bioavailability of nalidixic acid were
      examined in Rainbow Trout following i.v. and per os administration (5 mg/kg). 2.
      Nalidixic acid was biexponentially eliminated from plasma following i.v. dosing
      (t1/2 alpha = 0.06 h, t1/2 beta = 23.0 h). The volume of distribution (Vss) and
      total body clearance (Clb) were 964.7 ml/kg and 31.5 ml/kg/h, respectively. 3. In
      vitro plasma protein binding was specific and saturable over a range of
      concentrations from 0.43 microM to 20.0 mM. Binding was approx. 26% at
      kinetically relevant plasma concentrations. 4. Apparent oral bioavailability was
      determined to be > 100%, suggesting that nalidixic acid was largely bioavailable
      and non-linear pharmacokinetics were evoked. 5. Oral studies demonstrated the
      highest 14C nalidixic acid equivalent concentrations in bile, intestine and
      liver. Muscle contained intermediate concentrations but among all organs
      accounted for the greatest total amount of drug (12.2% of dose). Mass balance
      studies demonstrated composite values for per cent of dose administered of 23.7,
      18.8, 8.5, 10.0, 7.4 and 2.3% for 1, 2, 3, 6, 9 and 15 days, respectively. 6. A
      glucuronic acid conjugate of nalidixic acid was identified by n.m.r. and mass
      spectral analysis as the single primary metabolite.

PMID- 8291265
TI  - Microbial models of mammalian metabolism: involvement of cytochrome P450 in the N
      demethylation of N-methylcarbazole by Cunninghamella echinulata.
AB  - 1. As previously reported (Yang and Davis 1992), N-methylcarbazole (NMC) is
      converted to N-hydroxymethylcarbazole (NHMC), and 3-hydroxy-N
      hydroxymethylcarbazole (3-OH-NHMC), two relatively stable carbinolamine
      metabolites by the fungus Cunninghamella echinulata (ATCC 9244). Decomposition of
      these two carbinolamines yields the corresponding dealkylated metabolites,
      carbazole and 3-hydroxycarbazole. In the present study, the possible involvement
      of cytochrome P450 in the requisite N-alkyl hydroxylation reaction was examined.
      2. Carbon monoxide, a classical P450 inhibitor, markedly inhibited the formation
      of NHMC, as did potassium cyanide. 1-Benzylimidazole, piperonyl butoxide and SKF
      525A inhibited the formation of both NHMC and 3-OH-NHMC, while beta
      naphthoflavone (5,6-benzoflavone) induced their formation. 3. The source of the
      oxygen atom in the metabolite NHMC was examined by GC/MS analysis of NHMC formed
      during incubation of NMC in H218O-enriched medium which resulted in no
      incorporation of labelled oxygen into the metabolite. 4. An intermolecular
      isotope effect was not observed for the formation of NHMC suggesting that C-H
      bond cleavage is not a rate limiting step in the formation of this metabolite
      under the conditions examined. 5. It was concluded that P450 enzymes may be
      involved in the N-demethylation of NMC catalyzed by this fungal model of
      mammalian metabolism, and provides further support for biochemical and
      mechanistic parallels between mammalian metabolism and microbial systems
      catalyzing phase-1 biotransformations.

PMID- 8291266
TI  - In vitro studies on the interaction of the pyridoindole antioxidant stobadine
      with rat liver microsomal P450.
AB  - 1. Stobadine, a pyridoindole antioxidant agent, elicited medium affinity, low
      capacity interaction with type I binding sites of the hepatic microsomal
      cytochromes P450 derived from control and acetone-pretreated rats. Reverse type I
      interaction of low affinity and low capacity was observed in microsomes from
      phenobarbital-treated rats. 2. Stobadine led to an increase of H2O2 production
      when added to liver microsomes derived from differently pretreated rats in an
      NADPH-dependent process with concomitantly increased oxygen consumption. 3.
      Stobadine, at concentrations stimulating H2O2 formation, was found to prevent
      NADPH-induced microsomal lipid peroxidation, assessed as thiobarbituric acid
      reactive product accumulation. 4. Only a weak inhibitory effect of stobadine on
      either NADPH- or cumene hydroperoxide-dependent aminopyrine N-demethylation and
      aniline hydroxylation was observed in microsomes from control and phenobarbital
      pretreated rats. An approximately 10 times higher inhibitory potency towards
      aminopyrine N-demethylase activity was observed in acetone-pretreated rats. 5. In
      spite of the direct interaction of stobadine with microsomal P450, the compound
      only marginally affected aminopyrine and aniline metabolism both by monooxygenase
      and peroxidase modes of action of the P450 enzyme system. The potent antioxidant
      activity of stobadine was not diminished by the ability of the drug to stimulate
      the oxidase function of P450.

PMID- 8291267
TI  - Bioavailability and disposition of 3H-solanine in rat and hamster.
AB  - 1. The toxicokinetics of [3H]-alpha-solanine after oral (p.o.) and intravenous
      (i.v.) administration in rat and hamster were studied, in order to decide which
      is the most appropriate model in risk assessment studies. The i.v. dose was 54
      micrograms/kg; the oral dose was 170 micrograms/kg. 2. After i.v. administration,
      the toxicokinetics of total radioactivity in blood were comparable in rat and
      hamster. However, the clearance of total radioactivity from plasma was more
      effective in rat than in hamster. The half-lives of distribution and of the
      terminal phase of unchanged alpha-solanine were not different between rat and
      hamster, whereas the systemic and metabolic clearance were, respectively, about
      1.6 and 2.7 times higher in rat than in hamster. The clearance of unchanged alpha
      solanine is more effective than of total radioactivity. 3. After p.o.
      administration in rat and hamster, the mean bioavailability of total
      radioactivity is about 29 and 57%, respectively. The bioavailability of unchanged
      alpha-solanine is only 1.6 and 3.2%, respectively, when compared with i.v.
      administration. 4. T1/2el of alpha-solanine after p.o. administration was in rats
      a factor of four and in hamsters a factor of two shorter than after i.v.
      administration. A strong retention of radioactivity was seen in the hamsters
      after p.o. administration; only 40% of the dose was excreted within 7 days versus
      90% in rat. 5. Based on these and toxicological data from literature, it was
      decided that the hamster is a more appropriate model in (sub)-chronic toxicity
      studies with alpha-solanine than the rat.

PMID- 8291268
TI  - [Clinical aspects, diagnosis and therapy of pulmonary embolism].
AB  - Pulmonary embolism is a frequent and malignant complication of other diseases. To
      consider this is the most important step. ECG, pO2/pCO2, chest X-ray are used for
      differential diagnosis; pulmonary embolism is directly confirmed by scintigraphy,
      echocardiography, pulmonary angiography and pulmonary artery catheterisation,
      supplemented by examination of lower venous system (sonography, phlebography).
      Small emboli should also be noted as a signal of dangerous recurrence. The choice
      of the therapeutic method (embolectomy, fibrinolysis, anticoagulation) depends on
      the severity of pulmonary embolism, available methods and present
      contraindications. Depending upon the severity and general condition of the
      patient, it may be necessary to disregard possible contraindications against
      therapeutic methods that may cause desobliteration. Anticoagulation is used as
      prophylactic method, in exceptional cases a blockade is applied to the vena cava
      inferior.

PMID- 8291269
TI  - [Pathophysiology of pulmonary hypertension and chronic cor pulmonale].
AB  - Pulmonary circulation has become possible only by right heart catheterisation.
      The point of increased pressure in relation to pulmonary capillary wedge pressure
      is divided into postcapillary (passive), capillary and precapillary (active)
      pulmonary hypertension (PH). We assume that reduction of alveolar oxygen partial
      pressure leads to a growth of mast cells not only peribronchially, but also
      especially perivascularly, causing pulmonary arteriolo-vasoconstriction during
      release of eicosanoids (mediators). The individual components (vasoconstrictive,
      obliterative, obstructive, reactive, nutritive, primary, porto-pulmonary) are
      discussed. Long-term elevated pulmonary artery pressure (increased arterial
      vasoconstriction) results in right heart hypertrophy, which begins particularly
      in the right heart ejection tract. Depending on the underlying parenchymal or
      vascular diseases, we must differentiate between chronic cor pulmonale
      parenchymal or vascular. Right ventricular catheterisation may be differentiated
      into compensated or decompensated situation. Timely normalisation of pulmonary
      artery pressure may even lead to regression of the right ventricular hypertrophy.
      Right ventricular contractility on hypoxia is basically different in adapted and
      non-adapted patients (important for therapy and prognosis). Progression of right
      ventricular muscle mass and constant myocardial vasculature will cause
      stenocardias; in that case, permanent oxygen insufflation is indicated. Right
      ventricular hypertrophy affects the left heart, conducting alteration in
      pulmonary circulation (pulmo cardialis).

PMID- 8291270
TI  - [Current aspects in diagnosis of chronic cor pulmonale].
AB  - Pulmonary hypertension occurs frequently in patients with chronic obstructive
      lung diseases and contributes to a poor prognosis. Most common symptoms in
      addition to dyspnea, cough and expectoration are fatigue, syncopes, chest pain
      and peripheral oedema. No single non-invasive method such as lung function
      testing, blood gas analysis, ECG, chest x-ray, myocardial scintigraphy and
      isotopic radionuclide ventriculography is sufficiently reliable for predicting
      pulmonary hypertension. Only the combination leads to the diagnosis of pulmonary
      hypertension and cor pulmonale within acceptable limits. Echocardiography was
      found to be a reliable method of assessing right ventricular function. Doppler
      echocardiography is most useful with a specificity and sensitivity of about 80%.
      As "golden standard" cardiac catheterisation is still required for the
      measurement of pulmonary artery pressure (PAP), pulmonary vascular resistance
      (PVR), cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) at rest
      and exercise.

PMID- 8291271
TI  - [Noninvasive diagnosis of pulmonary hypertension in patients with COPD using
      regression and discriminant analysis].
AB  - The evidence of elevated non-invasive parameters in prediction of pulmonary
      hypertension was examined in 168 patients with chronic obstructive pulmonary
      disease (COPD). Forced vital capacity (FVC), Tiffeneau-test (FEV1), oxygen
      partial pressure, x-ray ascertained diameter of right descending branch of
      pulmonary artery (RDB), myocardial scintigraphy, and right ventricular ejection
      fraction showed significant differences between patients with and without
      pulmonary hypertension. Neither of them alone allows prediction of pulmonary
      pressure exactly, only in combination non-invasive parameters are usable. In non
      invasive diagnosis of catheterisation we suggest to use a regression function
      including FEV1, FVC and RDB by an ascertained specificity of 80% and sensitivity
      of 75%. To classify the patients according to normal and increased pulmonary
      artery pressure, FEV1, RDB and myocardial scintigraphy by a discriminant function
      with specificity/sensitivity of 80%, are relevant parameters. Accurate diagnosis
      of latent pulmonary hypertension requires right heart catheterisation. The domain
      of non-invasive diagnosis is screening and therapy monitoring of pulmonary
      hypertension, or if right heart catheterisation is contraindicated.

PMID- 8291272
TI  - [Therapy of chronic cor pulmonale].
AB  - Treatment of chronic cor pulmonale consists in therapy of causing disease and
      early influence of pulmonary hypertension. Long-time oxygen therapy is proved to
      be an effective measure of live support. Drug effects on pulmonary hypertension
      up to now are unsatisfactory. In special cases vasodilators have to be checked on
      responder rate. Right heart decompensation requires an in-patient treatment;
      physical rest, oxygen insufflation and diuretics are reliable.

PMID- 8291273
TI  - [Synopsis of the interactions of heart and lung function].
AB  - Due to the close connection between the functions of heart and lung there are no
      pathological changes in the one system without altering the physiology of the
      other. The interactions between heart and lung and their possible reactions are
      shown in some selected examples. On the one hand, in advanced lung diseases and
      in cor pulmonale one has to be on the look-out for concomitant disturbances of
      the left ventricular function for diagnosis, prognosis and therapy and on the
      other hand, there are deteriorations of chronic heart diseases due to secondary
      bronchopulmonary diseases. The treatment of combined cardiopulmonary disorders
      requires particular care.

PMID- 8291274
TI  - [Primary pulmonary hypertension].
AB  - In 1% of the patients with cor pulmonale the cause of the high pulmonary artery
      pressure remains unclear. The underlying severe and mostly progressive pulmonary
      vascular disease with unknown aetiology is defined as primary pulmonary
      hypertension (PPH) with three different pathomorphological subtypes, plexogenic
      pulmonary arteriopathy (PPA), thrombotic pulmonary arteriopathy (TPA) and
      pulmonary venoocclusive disease (PVOD). The endemic occurrence of PPH after the
      ingestion of anorexigenic drugs (aminorex fumarate) and toxic rapeseed oil lead
      to the hypothesis that PPH is a pulmonary vascular reaction to exogenous toxic
      agents on the base of a genetic disposition. The initial response could be an
      endothelial cell dysfunction leading to pathological proliferation of vascular
      smooth muscle cells, vasospasm and local disturbances of haemostasis. The derived
      therapeutic concepts with vasodilators (high dose calcium channel-blocking
      therapy, prostacyclin) and with anticoagulant drugs show some encouraging
      results. The lung and heart-lung transplantation have become real therapeutic
      options for the patients with PPH considering the mostly still very unfavourable
      prognosis of PPH.

PMID- 8291276
TI  - Differential diagnosis of adenomas and dysplastic lesions in patients with
      ulcerative colitis.
AB  - In a retrospective study, unequivocal neoplastic lesions (126 circumscribed
      lesions, 10 large-area lesions) in 76 patients with known ulcerative colitis were
      classified into adenomas and dysplastic lesions on the basis of
      pathomorphological criteria. The macroscopic appearance, gland architecture,
      mucin vacuoles, the appearance of the nucleus, the stroma/gland ratio, the
      position of the proliferation zone, the interface between the lesion and the
      surrounding mucosa, and the state of neighbouring mucosa were all assessed. In 31
      patients (41%), the lesions were classified as adenomas, in 42 patients (55%) as
      dysplastic lesions. A further three patients (4%) were found to have both
      adenomas and dysplastic lesions. The average age of the patients with adenomas
      was 66.0 years, that of those with dysplastic lesions 43.4 years. The mean
      duration of the disease in patients with adenomas was 7.2 years, and in patients
      with dysplastic lesions 12.6 years. Among the patients with adenomas, 65% has
      solitary and 35% multiple lesions; among the patients with dysplastic lesions,
      the corresponding figures were 27% and 73%. No significant differences were found
      in sex distribution, the extent of the ulcerative colitis or the site of the
      lesions. Successful differentiation between adenomas and dysplastic lesions in
      ulcerative colitis patients requires a differentiated therapeutic response.

PMID- 8291275
TI  - Predictive diagnosis in familial adenomatous polyposis: evaluation of molecular
      genetic and ophthalmologic methods.
AB  - Familial adenomatous polyposis (FAP) is an autosomal-dominant precancerous
      condition characterized by the appearance of hundreds to thousands of colorectal
      polyps. The responsible gene (APC) has been mapped and identified. The cancer
      prevention policy for persons at risk (children and sibs of FAP patients) implies
      an early diagnosis of the disease. A presymptomatic diagnosis allows to limit the
      regular rectosigmoidoscopic examination to those persons having inherited the
      disease gene. Presymptomatic diagnosis can be achieved by molecular genetic
      methods (direct and indirect genotype analysis) and by funduscopic examination of
      retinal pigment anomalies that are characteristic for FAP. The aim of this study
      was to examine the power of the molecular genetic and ophthalmologic methods for
      presymptomatic diagnosis in FAP. For this purpose 60 FAP families with 171
      persons at risk were examined. By direct mutation analysis a presymptomatic
      diagnosis was achieved in 32% of the persons at risk; indirect genotype analysis
      was possible in 88% of the families in which more than one FAP patient was
      available. The ophthalmologic examination allowed a presymptomatic conclusion in
      79% of the persons at risk. In no case there was a discrepancy in the results
      between the methods applied. The ophthalmologic presymptomatic test is useful
      especially in families where the index patients has a new mutation in the APC
      gene that has not been identified.

PMID- 8291277
TI  - The management of enterocutaneous fistulas with parenteral hyperalimentation.
AB  - During a period of nine years, all patients with enterocutaneous fistula who
      received parenteral nutrition as part of therapy were evaluated retrospectively.
      Twenty-three patients were studied. Peptic ulcer was the most common primary
      disease, with the fistula arising in 78 percent of the cases from the breakdown
      of an anastomosis and in the remainder from a direct trauma to the bowel. The
      most common site of the fistulas was the ileum followed by the duodenum. All the
      patients were treated conservatively with total bowel rest and parenteral
      nutrition, and in 56.5 percent of the cases spontaneous closure occurred within
      an average of 29.6 days. In five patients, the fistula failed to close, and
      surgery was performed. The mean surgical closure time overall 36.4 days, but this
      varied from 20.8 days for the duodenum to 39 days for the jejunum and ileum, and
      19.7 days for the large intestine. Five patients (22.7%) died, four from sepsis,
      the fifth from systemic malignancy. Mortality was related to the location and
      output of the fistula, with jejuno-ileal high-output fistulas in particular
      figuring prominently in the mortality.

PMID- 8291278
TI  - Intestinal absorption and malnutrition in patients with the acquired
      immunodeficiency syndrome (AIDS).
AB  - The relation of small intestinal dysfunction and malnutrition (body composition
      and serum index parameters of nutrition) was investigated in 36 male patients
      with AIDS. Mucosal absorptive capacity was assessed by the 25 g D-xylose test. D
      xylose absorption (2 h - serum profile and 5 h - urine) classified 17 patients as
      having impaired and 19 patients as having normal absorption. In both groups body
      weight, body mass index as well as body composition analysis indicated
      malnutrition when compared to healthy male controls (n = 340) or asymptomatic HIV
      infected patients (n = 26). Patients with abnormal D-xylose test had more severe
      malnutrition indicated by a lower body cell mass (17.7 +/- 5.4 vs. 22.5 +/- 4.5
      kg; p < 0.01) and an increased ratio of extracellular mass to body cell mass
      (1.99 +/- 0.82 vs. 1.45 +/- 0.46 p < 0.01). Total serum protein, albumin,
      cholinesterase activity, cholesterol and LDL were significantly diminished in
      AIDS-patients with abnormal D-xylose test compared to those with normal D-xylose
      absorption. Intestinal dysfunction indicated by decreased D-xylose Intestinal
      dysfunction indicated by decreased D-xylose absorption thus represents an
      important feature of malnutrition and wasting, and patients with abnormal D
      xylose absorption have more profound impairment of body composition, visceral
      proteins and lipids reflecting malnutrition than patients with unaffected
      intestinal absorption.

PMID- 8291279
TI  - [Eosinophilia as the leading symptom of highly malignant enteropathy-associated T
      cell lymphoma].
AB  - A 39 year old man had been suffering from chronic bowel symptoms of changing
      intensity. At the age of 37 the diagnosis of nontropical sprue was made. After
      institution of a gluten free diet the patient improved, but soon diarrhea started
      again. In the examination of peripheral blood smear, bone marrow and small
      intestinal mucosal biopsies a dominant eosinophilia was found. Since several
      attacks of abdominal colics and finally an acute abdomen occurred, a laparotomy
      was indicated. This operative intervention showed a perforation of the intestine
      and tumors in the bowel wall as well as numerous lymphomas spread over the whole
      mesentery. The histological examination of both the small intestine resect and
      the lymphomas proved the diagnosis of a highly malignant Non Hodgkin lymphoma
      (middle and large cell pleomorphic T-cell lymphoma with transition into a large
      cell anaplastic lymphoma [ki-1 lymphoma]). The patient received a chemotherapy
      with COEP but died 4 weeks after the surgery.

PMID- 8291280
TI  - Brucellosis: differential diagnosis of acute abdominal pain.
AB  - A 34-year-old Turkish woman presented with septic fever, sweats, arthralgia, and
      abdominal pain. Further examination revealed generalized lymphadenopathy,
      hepatosplenomegaly, pancytopenia, and multiple caseous granulomas.
      Microbiological diagnosis revealed Brucella melitensis type 3 as causative agent.
      This case report demonstrates that abdominal pain can be a symptom in
      brucellosis, and caseous granulomas may occur. In our mobile society Brucella
      infection should be considered as possible differential diagnosis in patients
      with fever, lymphadenopathy, hepatosplenomegaly, and pancytopenia, although human
      brucellosis is rare in Germany and other Western countries.

PMID- 8291281
TI  - [Endoscopic argon gas coagulation--initial clinical experiences].
AB  - Argon-gas-coagulation represents a new method of contact free electrocoagulation,
      where RF-energy is applied to the tissue by means of ionized argon-gas. In the
      operative field argon-gas-coagulation has been used with success for hemostasis
      in several parenchymatous organs and for devitalization of various tissues.
      Experimental studies have shown the superiority of argon-gas-coagulation over
      standard electrocoagulation and surgical techniques due to its high efficiency
      and limited tissue traumatization. Having developed and designed special
      endoscopic probes and after in-vitro-studies we could utilize the method in
      flexible endoscopy as well. From June 1991 to September 1992, 102 patients were
      treated in 189 sessions with argon-gas-coagulation in the upper and lower
      gastrointestinal tract as well as respiratory system. The indications were:
      malignant and benign tumors, diffuse hemorrhages of various origins and of
      various sites, tissue overgrowth after stent-implantation, remaining tissue after
      endoscopic adenomectomy and conditioning of fistulas prior to fibrin sealing. In
      all cases argon-gas-coagulation in flexible endoscopy has been shown to be a very
      effective and easy to perform technique with advantages in comparison to standard
      electrocoagulation. Problems and complications have not been observed. The
      limited depth of tissue penetration (2-3 mm) coincident with efficient tissue
      coagulation allows the application even in critical areas such as the duodenum or
      colon. In many indications argon-gas-coagulation has replaced the former widely
      used Nd-YAG-laser in our unit. Except vaporisation of extended tumors, the argon
      gas-coagulator shows remarkable advantages for nearly all applications.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8291282
TI  - [Perioperative multi-modality treatment strategies in esophageal cancer].
AB  - In order to improve the prognosis of patients with cancer of the esophagus,
      perioperative combined treatment modalities have been designed. The positive
      effect of an additional preoperative chemotherapy and of a pre- or postoperative
      radiotherapy has not been proven consistently until now. Neoadjuvant
      radiochemotherapy induces a pathohistologic complete remission in one quarter of
      the patients. The results of radiochemotherapy without operation in esophageal
      carcinomas look promising. However, their exact value has still to be
      investigated in randomized studies.

PMID- 8291283
TI  - [Possible physiologic functions of endogenous carbon monoxide].

PMID- 8291284
TI  - [Octreotide is ineffective in prevention of ERCP-induced pancreatitis].

PMID- 8291285
TI  - [Successful treatment of recurrent lower gastrointestinal hemorrhage in
      intestinal angiodysplasia with an estrogen-progesterone combination].

PMID- 8291286
TI  - Laxative use not a risk for colorectal cancer: data from the Melbourne colorectal
      cancer study.

PMID- 8291287
TI  - [Oral anticoagulation for prevention of thromboembolism in non-rheumatic atrial
      fibrillation: indications, effectiveness and risk].
AB  - Oral anticoagulation in patients with rheumatic heart disease for prevention of
      systemic thromboembolism is accepted clinical practice. The incidence of stroke
      in patients with nonrheumatic atrial fibrillation is about five times the rate of
      patients in sinus rhythm. However, contradictory findings in several small
      retrospective studies have precluded determination of a gold standard for
      patients with nonrheumatic atrial fibrillation so far. Recently, the results of
      five prospective, placebo-controlled studies in patients with nonrheumatic atrial
      fibrillation treated with anticoagulation have been published. A consistent risk
      reduction of thromboembolism ranging from 37 to 87% in patients treated with
      warfarin was reported. This risk reduction occurred in excess of a relatively low
      incidence of intracerebral and/or fatal bleeding complications. The efficacy of
      prevention of thromboembolism was comparable for high intensity anticoagulation
      (International Normalized Ratio (INR) 2.8-4.2) and low dose anticoagulation (INR
      1.5-2.7). However, fatal and/or intracerebral bleedings only occurred with INR >
      or = 2.6. In subgroup analysis, recent congestive heart failure, arterial
      hypertension, and previous apoplex or arterial thromboembolism were independent
      clinical predictors of increased risk for thromboembolism, whereas results in
      patients with chronic and intermittent atrial fibrillation were comparable. In 69
      patients with lone atrial fibrillation, no single event occurred in the follow-up
      period. Thus, lone atrial fibrillation does not seem to carry an increased risk
      for stroke when strict criteria for diagnosis of lone atrial fibrillation are
      applied. In two of the five studies, aspirin was additionally randomized. Since
      contradictory findings resulted, the role of aspirin for prophylaxis of stroke
      still needs to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291288
TI  - [Familial idiopathic atrial fibrillation with bradyarrhythmia].
AB  - Based upon a report of a 10-year-old boy, familial occurrence of idiopathic
      atrial fibrillation with bradyarrhythmia is presented. An autosomal dominant
      trait seems possible.

PMID- 8291289
TI  - [Low energy cardioversion with the implantable cardioversion defibrillator
      devices for treatment of ventricular tachycardia and ventricular fibrillation].
AB  - Programmable implantable cardioverter-defibrillators (ICD) with low energy
      capabilities for the treatment of ventricular tachycardia were introduced to
      increase patients acceptance and lengthen battery life. However, no data about
      efficacy and safety of low energy cardioversion with subsequent defibrillation in
      ventricular tachycardia and fibrillation are available. Nineteen of 42 patients
      with documented or inducible ventricular tachycardia before ICD implantation were
      studied. In all patients the effectiveness of low-energy cardioversion (< or = 4
      joules) with subsequent high-energy defibrillation was evaluated in monomorphic
      ventricular tachycardia and/or ventricular fibrillation. During predischarge
      programmed stimulation in 13/19 patients, a total of 32 monomorphic ventricular
      tachycardias occurred, and in only six patients could ventricular fibrillation be
      induced. A tachycardia-related efficacy of 69% and patient-related efficacy of
      46% of the low-energy cardioversion < or = 4 joules was observed. Ten
      tachycardias were accelerated to ventricular fibrillation or remained unchanged
      (n = 2). The second shock (energy > 17 joules) terminated seven arrhythmias,
      whereas a third (30 joules) shock or an external defibrillation (n = 2) was
      necessary for termination of the remaining three arrhythmias. After induction of
      ventricular fibrillation as the primary arrhythmia, the first (low-energy) shock
      terminated 2/16 episodes, whereas the second (high-energy) shock reverted
      ventricular fibrillation in 11/16 episodes. In one patient, a second high energy
      shock and in two patients external defibrillation was necessary for conversion of
      ventricular fibrillation. In one patient, an increase of the defibrillation
      threshold induced by amiodarone could be identified.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8291290
TI  - [Quantification of postoperative pulmonary valve insufficiency: severity and
      clinical symptoms].
AB  - Surgical treatment of pulmonary stenosis may lead to inevitable valvular
      incompetence. The hemodynamic and clinical significance of post-operative
      pulmonary insufficiency (PI) is uncertain. In patients presenting cardiomegaly
      and reduced exercise tolerance reoperation may be considered. However, pulmonary
      valve replacement remains controversial. In order to elucidate the relevance of
      PI in the long-term post-operative course, quantitative data of PI were compared
      with chest radiographs and the physical condition. Thirty-one patients with a
      mean age of 18.5 years (3-36 years) were studied. Twenty-two patients had
      surgical correction of Tetralogy of Fallot (TOF) and nine had commissurotomy of
      pulmonary valve stenosis (PS). Catheterization was performed, on average, 12.9
      years (2-29 years) after operation in 68% of cases with an interval of more than
      10 years. PI was quantitated by digital roentgen densitometry. Regurgitant
      fraction (RGF) ranged between 13-61%, according to a right ventricle volume load
      index (VBI) of 1.15-2.6 (ratio of total to effective stroke volume). Twenty of 31
      patients (12 TOF, 8 PS) had PI as the only significant lesion. VBI (1.15-2.6)
      correlated with the cardio thoracic ratio (0.50-0.64), r = 0.74. All patients
      were in good physical condition. 11 actively took part in sports: all of the
      eight patients studied by ergometry met normal conditions. Four patients had
      antiarrhythmic medication. Eleven of 31 patients had PI and additional
      abnormalities: tricuspid insufficiency (4), right ventricular pressure overload
      (5), ventricular septal defect (1), depressed left ventricular function (5), and
      aortic insufficiency (3).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291291
TI  - [Cor triatriatum sinistrum--value of pulmonary vein flow in hemodynamic
      assessment].
AB  - We report on two patients (a 52-year-old female and a 32-year-old male) with cor
      triatriatum sinistrum, both clinically inconspicuous. The former had undergone
      strenuous athletic training without difficulty for eight years of her youth. In
      both cases, cor triatriatum sinistrum was found by chance during transthoracic
      echocardiography undertaken for hypertension. The exact insertion-site of the
      left atrial membrane only became apparent by using biplane transoesophageal
      echocardiography. Neither of the patients showed associated cardiac malformation.
      Hemodynamics were evaluated by pulsed waved Doppler analysis of pulmonary venous
      flow profile; no signs of inflow obliteration into the left atrium were found in
      either case.

PMID- 8291292
TI  - [Brain abscess in congenital cyanotic heart defect in adulthood].
AB  - A 27-year-old patient with pulmonary atresia, ventricular septal defect, and
      multifocal lung-perfusion suddenly developed headache and left facial sensory
      disturbances. Using computed tomography and magnetic resonance imaging a temporo
      parietal brain abscess was diagnosed. After abscess aspiration and antibiotical
      therapy neurological signs disappeared immediately and the patient could leave
      hospital without any neurological deficit. Adult patients with congenital
      cyanotic heart disease are at risk to develop a brain abscess which should
      therefore be ruled out if headache, fever of unknown origin or focal neurologic
      signs occur.

PMID- 8291293
TI  - [Incidence, predisposing factors, acute complications and prognostic significance
      of intracoronary thrombus formation during PTCA].
AB  - Besides coronary artery dissection, intracoronary thrombus formation is known to
      be an important mechanism for acute coronary occlusion in the course of
      percutaneous transluminal coronary angioplasty (PTCA). Therefore, we analyzed 210
      consecutive patients (217 dilated stenoses) to define the incidence and potential
      predisposing clinical and morphological factors of intracoronary thrombus
      formation. Intracoronary thrombus formation was angiographically detectable in
      11% of the cases, a dissection in 21%. Acute PTCA-related coronary occlusion
      (incidence = 5.5%) was significantly associated with intracoronary thrombus
      formation (p < 0.001) but less so with dissection (p = 0.074). Acute redilatation
      after an initially successful PTCA was almost exclusively necessary in patients
      with intracoronary thrombus formation (p < 0.001). Univariate analysis
      demonstrated the following factors to be significantly associated with
      intracoronary thrombus formation: Irregular lumen of stenosis (p = 0.006),
      stenosis at branch point (p = 0.012) and unstable angina pectoris (p = 0.001).
      Patients with intracoronary thrombus formation did not show a worse long-term
      prognosis regarding clinical events compared with a matched group (average follow
      up of 20 months). CONCLUSION: Luminal irregularities within the stenosis to be
      dilated and the clinical syndrome of unstable angina pectoris are predisposing
      factors for PTCA-induced intracoronary thrombus formation, suggesting that
      preexisting local activation of the coagulation system plays an independent role
      for intracoronary thrombus formation during PTCA. Although intracoronary thrombus
      formation increases the risk for acute complications during PTCA, the long-term
      result is not adversely affected.

PMID- 8291294
TI  - [Acute pericardial tamponade after percutaneous transluminal coronary angioplasty
      (PTCA). A rare life threatening complication].
AB  - Cardiac tamponade following coronary perforation is a rare complication in
      conventional balloon angioplasty. In a series of 8000 dilatations we observed
      this complication after PTCA in 2 female patients (0.25/1000). In both cases
      cardiac tamponade occurred 2 h after PTCA of small, in 1 case calcified, coronary
      arteries during monitoring on the coronary care unit. By immediate percutaneous
      pericardiocentesis and subsequent drainage by a pigtail catheter we could manage
      the complication. One patient suffered an acute myocardial infarction 3 days
      after PTCA because of a subacute occlusion of the perforated vessel.

PMID- 8291295
TI  - [Extraction of a ruptured PTCA balloon catheter].
AB  - While attempting angioplasty of a very tight and long circumflex lesion with a
      metal-shafted monorail catheter, the flexible part of the balloon catheter shaft
      broke off within the guiding catheter. The lost piece of catheter was then
      retrieved from the coronary artery by using an on-the-wire balloon catheter that
      was inflated inside the distal end of the guiding catheter.

PMID- 8291296
TI  - [Report on the "Angiology" Study Group Meeting in Mannheim 15 April 1993].

PMID- 8291297
TI  - [Stockholm's models--Stockholm's Health Care County Council's advice: health care
      quality will give way when money does not last].

PMID- 8291298
TI  - [Nurses are responsible for not using violence against patients].

PMID- 8291299
TI  - [Enjoyable meals are key to improvements].

PMID- 8291300
TI  - [Nursing care record an assurance for everybody. Interview by Jan Thomasson].

PMID- 8291301
TI  - [Responsibility for good and safe care wanted by nurses].

PMID- 8291302
TI  - [Stockholm's models--models for the strong].

PMID- 8291303
TI  - [Stockholm's models--in Taby enterprise blooms].

PMID- 8291304
TI  - [Stockholm's models--South in the city they defend themselves against
      privatization].

PMID- 8291305
TI  - [Stockholm's models--it is all about money in the health care market. Interview
      by Carina Roxstrom].

PMID- 8291306
TI  - [Stockholm's models--chaos and uncertainty in Stockholm's laboratories].

PMID- 8291307
TI  - [Stockholm's models--take initiative yourself urges the SHSTF. Interview by
      Carina Roxstrom].

PMID- 8291308
TI  - [Disaster team at work. Qualified treatment even at the accident site].

PMID- 8291309
TI  - [Disaster practice puts finishing touch to routines. Interview by Birgitta
      Dalenstam].

PMID- 8291310
TI  - [Psychological intervention. Those stricken by crisis need long-term support].

PMID- 8291311
TI  - [Concern about curtailed diabetes care].

PMID- 8291312
TI  - [Frostbite. General cooling can be life-threatening].

PMID- 8291313
TI  - [Whooping cough study--Goteborg's research can provide a new vaccine].

PMID- 8291314
TI  - [Shock wave treatment. Kidney stones crushed when sound waves emit energy].

PMID- 8291315
TI  - [Laparoscopic surgery--careful method makes for short-term stay].

PMID- 8291316
TI  - [Sisters lost in Stockholm's family physician model--"we still want to have the
      nursing care responsibility". Interview by Kaj Nyman].

PMID- 8291317
TI  - [Fund's money is withdrawn for Smedangen. Interview by Carina Roxstraom].

PMID- 8291318
TI  - [How shall we handle our knowledge in gene technology?. Interview by Elisabet
      Forslind].

PMID- 8291319
TI  - [Jobs disappear but the work goes on].

PMID- 8291320
TI  - [The new unemployment hits women first].

PMID- 8291321
TI  - [Everything can be subject to competition].

PMID- 8291322
TI  - [How does one manage?].

PMID- 8291323
TI  - [Communication between the public health physician and the community, especially
      via media channels].

PMID- 8291324
TI  - [Comments: ethics and epidemiological research].

PMID- 8291325
TI  - [The effect of perennial partnerships on the prospective development in the AIDS
      epidemic].
AB  - Long-term predictions of the AIDS epidemic in the general population are possible
      only on the basis of an epidemiologic model which contains explicit assumptions
      about partner choice and duration of partnerships. Several models proposed
      heretofore predict too many AIDS cases in the next century, because they neglect
      the correlation between ages of partners. In heterosexuals it is frequent that
      many years pass between acquisition and transmission of HIV. Therefore, the
      correlation implies that most infection chains are disrupted because the age in
      the year of infection increases as new links are added to a chain. These
      considerations can be put into quantitative terms by adapting the classical
      concept of the basic reproductive rate to the special situation of HIV infection.
      In this way the impact of age preference and partnership duration on the spread
      of HIV is analyzed.

PMID- 8291326
TI  - [Chronic rheumatic symptoms and diseases: a representative longitudinal study
      based on data of the general local health insurance fund of Dortmund].
AB  - In a representative diachronous study, findings concerning the prevalence of
      utilisation of medical services by patients who chronically suffer from
      rheumatism, as well as the amount of X-ray diagnoses and temporary disablement of
      those patients are presented. In order to make this study, personal data of the
      local statutory health insurance fund of the city of Dortmund (a 5% random sample
      of insured in 1988) was collected. Diseases and complaints of the rheumatic
      variety are a frequent reason for the utilisation of out-patient medical
      services: 38.8% of the insured of the random sample (2513 out of 6478 insured of
      the random sample) were under medical treatment in 1988 because of rheumatic
      complaints. The study refers to the unselected totality of patients of
      established doctors, which means that it refers to all phases of the illness. The
      chronicity of the rheumatic complaints is investigated by means of an operational
      definition which aims at the continuity of treatment. 18.9% of the insured
      suffered from chronic rheumatic complaints. Vertebral syndromes and degenerative
      joint diseases represent the majority of chronic rheumatic complaints. 50% of the
      patients suffering from chronic rheumatism were X-rayed at least once a year;
      younger ones more frequently than the older ones. The percentage of rheumatic
      patients suffering from rheumatism who are at least once a year temporarily
      disabled does not vary with regard to the age-group; one can however state: the
      older the patients are, the longer does sick-leave per annum last.

PMID- 8291327
TI  - Relationships between leisure time physical activity for exercise and other
      health-related behaviors.
AB  - In this article the relationships between physical activity for exercise and
      other health-related behaviors is studied. The data analyzed were collected
      during 1991 by telephone in Glasgow and Edinburgh and concern 2418 male and 3053
      female respondents between 18 and 60 years of age. In the analysis, respondents
      who reported exercising less than once in the previous week were contrasted with
      respondents who reported exercising more often. Compared with respondents
      exercising less often, respondents who reported exercising more often reported
      being smokers and adding salt to their food significantly less often, and more
      often reported drinking alcohol, using low-fat spread and engaging in weight
      losing behavior. No significant relation was found between physical activity for
      exercise and seat-belt use among males and blood pressure checking among males
      and females.

PMID- 8291328
TI  - [Variations by canton in the use of medical observation centers of the disability
      insurance in Switzerland].
AB  - The Medical Observation Centres of the state Disability Insurance (COMAI) are
      specialized agencies serving the cantonal commissions of the Disability Insurance
      in Switzerland. Using data collected for each case examined by the COMAI,
      utilisation rates and rankings were established for each canton. Utilisation
      rates varied by a factor of 40 from one canton to the next. This observed
      variation is independent of the number of new cases presenting to the Disability
      Insurance and of the number of disability pensions granted. Rankings were also
      independent of denominators used to define utilisation rates. These results
      suggest possible non-uniform application of state directives concerning the use
      of the COMAI, and unequal access to these specialized agencies. The reasons for
      these variations are the object of a study now underway.

PMID- 8291329
TI  - [Efficacy of smoking prevention campaign in adolescents: critical review of the
      literature].
AB  - This review is intended to assist those interested in smoking prevention in young
      people in choosing the most efficient and cost-effective methods. The importance
      of a critical analysis of the abundant literature available on the topic before
      implementing a new programme is stressed. In view of the present knowledge,
      preventive methods should start at age 12 and extend up to age 18 through
      actualizing sessions. The most promising programme should include learning to
      resist to social pressures and a cognitive and developmental approach which
      anchor smoking prevention in the psychological evolution of the adolescent.
      Training of peers being disproportionate in regard to what can be expected from
      their intervention, one key element is the teacher's training in the technique of
      changing behaviour. Evaluation of methodology and of long term results should
      belong to any programme.

PMID- 8291330
TI  - Trends in suicide mortality in Europe, 1955-89.

PMID- 8291331
TI  - [The AIDS problem in Burundi and its prevention among young people].

PMID- 8291332
TI  - Voluntary HIV testing among pregnant women: data from the European HIV Prevalence
      Database.

PMID- 8291333
TI  - Prison reform to help control the spread of HIV.

PMID- 8291334
TI  - WHO estimate of HIV infection tops 14 million.

PMID- 8291335
TI  - Evaluation of Swiss National Programme on AIDS.

PMID- 8291336
TI  - Cancer incidence and mortality in Europe, 1983-87.

PMID- 8291337
TI  - Prevention of severe invasive Haemophilus influenzae type B infections by
      vaccination.

PMID- 8291338
TI  - [Hemoglobin C (alpha 2 beta 2 6Glu-->lys). Study of 19 heterozygote AC carriers
      and of 5 cases of double hemoglobinopathy SC].
AB  - This paper describes clinical findings in subjects heterozygous for hemoglobin C
      and in compound heterozygotes SC. Most of our patients were coming from lands
      bordering the Guinea Gulf, on the inside of the loop made by the river Niger and
      from Haiti, which was populated by African slaves coming mainly from the Golden
      Coast (actually Ghana). Heterozygotes are asymptomatic and do not suffer from
      anemia. Age at diagnosis is higher than for SCA, although one of our cases was
      diagnosed at age one. Overwhelming infections or major anemia were not observed.
      Basal hemolysis remained moderate. HbF levels were not increased as they may be
      in sickle cell anemia. Splenomegaly was observed in 2/5 patients. Among severe
      complications we encountered, we must mention one case of foetal death, one
      tibial infarct, one case of pure red cell aplasia caused by parvovirus B19
      infection, and one case of proliferative retinopathy.

PMID- 8291339
TI  - [Parasitological evaluation of the stool].
AB  - The parasitologic investigation performed without clinical orientation in a
      routine laboratory allowed to identify the most common parasites, often cysts of
      protozoa, using a minimal technique. A more accurate investigation (e.g.:
      concentration, extraction and flotation) was hampered by a too large number of
      systematic specimens. The use of an immersion objective improves the detection
      and identification of cysts of protozoa. There is still some controversy on the
      virulence of small amoebae, flagellates, Blastocysts and Entamoeba coli, the
      infection being often massive. AIDS should predispose to new parasitic diseases
      such as cryptosporidiosis and strongyloidosis. A careful examination of stools
      for parasites has become mandatory in view of the wide geographical origin of
      patients with a parasitic disease.

PMID- 8291340
TI  - [Study of a group of diabetic patients enrolled in the INAMI convention "Self
      monitoring of blood glucose"].
AB  - We have studied the clinical characteristics of 126 insulin-treated diabetic
      patients, mainly type I subjects, who regularly performed during 18 months home
      glucose monitoring. The numbers of strips used each month was of 60 +/- 33 (mean
      +/- lSD). During the study period, HbA1C levels decreased from 8.6 +/- 2.1 to 7.0
      +/- 1.3% (p < 0.001). A significant decrease of HbA1C was also observed in a
      subgroup of 30 patients, in whom insulin therapy scheme (number of injections a
      day) was similar before and during home glucose monitoring. Our results confirm
      the benefits of regularly performed home glucose monitoring.

PMID- 8291341
TI  - Neurosyphilis presenting with optic neuropathy. Report of a case and review.
AB  - A patient with neurosyphilis, presenting with severe ocular impairment due to
      optic neuropathy, is described. In such a case, a low index of clinical suspicion
      and improper use of syphilitic serologic tests may delay diagnosis. However,
      specific tests of serum and cerebrospinal fluid are mandatory for the diagnosis.
      Treatment evaluation necessitates the follow-up of serology and cerebrospinal
      fluid cell count. Recent changes of therapy recommendations in subjects with
      neurosyphilis and in those syphilitic patients co-infected with HIV are
      mentioned.

PMID- 8291342
TI  - [Bilateral ureteral amyloidosis manifested by anuria].
AB  - Ureteral amyloidosis is an uncommon disease. It usually presents as an ureteral
      stenosis and resembles ureteral malignancy. The lesion consists of localized
      amyloidosis, containing lambda light chains, the etiology of which remains
      unknown. Ureteral calcifications have been suggested to be pathognomonic. When
      the diagnosis of ureteral amyloidosis is considered preoperatively, a renal
      sparing surgery must be planned. We observed a case of bilateral ureteral
      amyloidosis presenting with anuria; the patient was treated with conservative
      surgery and colchicine. The renal function improved without recurrence and
      remained stable after 5 years of follow-up.

PMID- 8291343
TI  - [Mediastinal and pulmonary hydatidosis, bronchocentric granulomatosis and IgA
      glomerulonephritis].
AB  - A 71-year-old female patient suffering from repeated bronchopneumonia developed
      terminal renal failure related to an immunologic glomerulonephritis. Autopsy
      revealed mediastinal and pulmonary hydatid cysts, associated with a
      bronchocentric granulomatosis; this association has been reported only once
      before.

PMID- 8291344
TI  - Acute chest syndrome in sickle cell anaemia.
AB  - A patient suffering from sickle cell anaemia who presented with the acute chest
      syndrome is described. The syndrome is reported to be one of the commonest causes
      of death in adults suffering from sickle cell disease. As it is difficult at
      presentation to distinguish the syndrome from infection, it is usual to give
      treatment appropriate for both. Early exchange transfusion is thought to limit
      further damage from sickling and offers the best hope of recovery.

PMID- 8291345
TI  - Cytopathology of pleural effusions after radiotherapy.
AB  - The cytomorphology of pleural effusions following ionizing radiotherapy (IRT) has
      not been studied systematically. To determine if IRT produces alterations in
      pleural fluids that affect the cytopathologic interpretation of these specimens,
      two reviewers, without clinical information, independently assessed 55 specimens
      obtained following IRT and 39 control specimens obtained from nonirradiated
      cancer patients. None of the 24 cytologic features studied were identified
      significantly more frequently by both reviewers in the irradiated specimens. Only
      one feature (bizarre cells) was found to occur significantly more frequently in
      the irradiated specimens (36% versus 15%, P = .03) by either reviewer (reviewer
      B). Four other features showed a tendency to occur more frequently in the
      irradiated fluids by one or the other reviewer. They included degenerative
      changes (27% versus 13%, P = .09 [reviewer A]), smudgy chromatin (16% versus 5%,
      P = .09 [reviewer A]), large cytoplasmic vacuoles deforming the nuclei (44%
      versus 26%, P = .07 [reviewer B]) and cytomegaly (38% versus 23%, P = .12
      [reviewer B]). The utility of these five features in identifying irradiated
      specimens was rigorously retested in a second masked review conducted jointly by
      the two pathologists. None of these features was found more frequently in the
      irradiated specimens in the second analysis. The results suggest that IRT does
      not consistently produce distinctive cytologic changes in pleural effusions and
      that a history of IRT should not affect the interpretation of these specimens.

PMID- 8291346
TI  - Fine needle aspiration cytology of Langerhans cell histiocytosis involving the
      thyroid. A case report.
AB  - We present an unusual case of Langerhans cell histiocytosis (LCH) involving the
      thyroid gland initially diagnosed by fine needle aspiration biopsy in a 16-year
      old boy. The cytologic findings in LCH involving the thyroid include high
      cellularity, isolated Langerhans cells with prominent nuclear grooves,
      multinucleate Langerhans cells, eosinophils, lymphocytes and rare benign
      follicular cells. Confirmation of LCH was obtained by core biopsy, positive S-100
      protein immunohistochemical staining and the demonstration of Birbeck granules on
      electron microscopy. We present the complete clinicopathologic features of this
      case with a review of the literature and discussion of the differential
      diagnosis.

PMID- 8291347
TI  - Sclerosing hemangioma of the lung: a potential source of error in fine needle
      aspiration cytology.

PMID- 8291349
TI  - Microfilariae in a fine needle aspirate from a skin nodule.

PMID- 8291348
TI  - Primary squamous cell carcinoma of the breast presenting as a nipple discharge.

PMID- 8291350
TI  - Immunostaining of small cytologic specimens. Facilitation with cell transfer.
AB  - Immunocytochemical study of cytologic specimens is often limited by the number of
      slides containing diagnostic cells. This study examined the effectiveness of
      transferring cells from a single smear to multiple slides in order to perform a
      battery of immunocytochemical stains on limited material. Immunostaining
      performed on four effusions and five fine needle aspirates yielded the expected
      results for most of the antibodies commonly employed in diagnostic pathology.
      Background staining was generally low following cell transfer, and the morphology
      of the cells was preserved. These results suggest that cell transfer in
      combination with immunocytochemistry may prove useful in the cytologic diagnosis
      of malignant lymphoma, neuroendocrine neoplasms, prostatic and mammary
      adenocarcinoma, and other malignant tumors.

PMID- 8291351
TI  - Benign versus malignant papillary neoplasms of the breast. Diagnostic clues in
      fine needle aspiration cytology.
AB  - Benign and malignant papillary lesions of the breast can be difficult to
      distinguish in both cytologic and histologic preparations. To determine the
      cytologic features, we retrospectively analyzed 29 fine needle aspirates with a
      biopsy-confirmed diagnosis of papilloma or papillary carcinoma. They included 7
      intracystic papillary carcinomas, 6 invasive papillary carcinomas and 17
      intraductal papillomas. All cases were evaluated for cellularity, single
      epithelial cells, atypia and papillary fragments. A common pattern was increased
      cellularity, papillary groups and single columnar epithelial cells. Markedly
      increased cellularity was present in 10/12 carcinomas and 4/17 papillomas.
      Numerous single cells were present in 5/12 carcinomas and 2/17 papillomas. The
      majority of cases had only mild to moderate atypia. Papillary carcinomas
      displayed nuclear hyperchromasia and stratification surrounding stroma and in
      isolated clusters. In papillomas, nine cases had background apocrine metaplasia,
      foam cells and/or bipolar cells. Apocrine metaplasia was absent from all cases of
      papillary carcinoma. Two papillomas had marked nuclear atypia with background
      necrosis and inflammation. These unusual cases represented infarcted papillomas,
      a potential pitfall in the diagnosis of cancer. We conclude that markedly
      increased cellularity and numerous single cells favor a diagnosis of papillary
      carcinoma. More specific diagnostic clues are the cytologic findings of nuclear
      hyperchromasia, stratification and absence of benign background cells, such as
      apocrine metaplasia.

PMID- 8291353
TI  - Cell yield. ThinPrep vs. cytocentrifuge.
AB  - Cell yields on cytologic preparations made in the Cytospin II cytocentrifuge and
      the ThinPrep Processor were compared. Slides were prepared by each method using
      calibrated volumes (25 microliters) of cell suspensions from 13 nongynecologic
      specimens. Cell counts for each slide were calculated by counting cells in
      predetermined fields using a gridded reticle at 40 x magnification, then
      extrapolating to the total surface area of the preparation. The cell counts
      demonstrated that when processing equal amounts of cell suspension, the ThinPrep
      method retained three times as many cells as the cytocentrifuge method. The
      ThinPrep method, with a higher rate of cell recovery, may provide a valuable tool
      toward more accurate cytologic diagnosis, particularly for cytologic samples with
      small numbers of cells.

PMID- 8291352
TI  - Cervical cancer screening in Canadian Native women. Adequacy of the Papanicolaou
      smear.
AB  - Cervical cancer mortality remains high in Canadian Native women in British
      Columbia. Underutilization of the Provincial Cytology Screening Program by
      Canadian Native women has been documented. Another potential factor is the
      quality of specimens obtained. Proportions of unsatisfactory smears and smears
      lacking endocervical cells, which reflect the sampling technique, were compared
      between Canadian Native and other British Columbian women. The findings suggest
      that differences in the quality of cytologic smears do not explain the observed
      discrepancy in cervical cancer mortality between Canadian Native and non-Native
      populations.

PMID- 8291354
TI  - Herpesvirus mimics. A potential pitfall in endocervical brush specimens.
AB  - The recent media focus on inadequacies in cervical smear collection and
      interpretation has resulted in improved collection methods, such as endocervical
      brushes, as well as closer scrutiny of morphologic criteria. However,
      endocervical cell artifacts may be associated with these endocervical brushes.
      Recently in our laboratory a case of reactive-atypical endocervical cells that
      resembled the cytologic changes associated with Herpes simplex virus (HSV)
      infection resulted in a false-positive diagnosis of HSV infection. Of 14,622
      gynecologic specimens accessioned over 14 months, 459 cases with reactive
      endocervical cells and 117 with atypical endocervical cells were reported. These
      cases were reviewed by two independent observers with no knowledge of the prior
      diagnoses and were evaluated for four cytologic criteria considered diagnostic of
      HSV infection: multinucleation, margination of nuclear chromatin, ground glass
      chromatin and intranuclear inclusions. Nineteen cases were diagnostic/suggestive
      of HSV; 19 additional cases were identified as herpesvirus mimics. The original
      diagnoses, demographics, clinical data and method of collection were reviewed. In
      all but three cases an endocervical brush was the method of collection. Of the
      four criteria studied, only ground glass chromatin had both high sensitivity
      (95%) and specificity (95%). Intranuclear inclusions, while pathognomonic, had
      low sensitivity (42%). Altered endocervical cells that mimic herpesvirus are a
      potential pitfall in the diagnosis of HSV infection. Use of strict criteria,
      knowledge of the collection method and clinical history will avoid misdiagnosis.

PMID- 8291355
TI  - Multivariate statistical analysis of bile cytology.
AB  - Cytologic features predictive of carcinoma in bile fluid were characterized by a
      review of 35 cases (22 malignant and 13 benign). Thirty-two cytologic variables
      were subjected to a stepwise multiple regression model to separate the criteria
      best suited to the benign versus malignant groups. Six key criteria were selected
      as useful indicators of malignancy: loss of honeycomb arrangement, enlarged
      nuclei, loss of polarity, bloody background, flat nuclei and cell-in-cell
      arrangement. Three or more of these criteria were observed in carcinoma cases
      more often than they were in noncancer cases (P < .01). By using these criteria,
      the overall sensitivity of diagnosing carcinoma by bile cytology was 86.4%, and
      the specificity was 76.9%.

PMID- 8291356
TI  - Rehydration of air-dried smears with normal saline. Application in fluid
      cytology.
AB  - Ninety fluid specimens (30 each of urine, ascitic and pleural fluid) were studied
      by preparing three comparable smears. One was air dried for Giemsa stain, one wet
      fixed in 95% ethanol and one dried on a hot plate at 37 degrees C, rehydrated in
      normal saline for 30 seconds and fixed in ethanol. The latter two were stained
      with Papanicolaou stain, and a comparison was made of the (1) retention of red
      blood cells, (2) retention of epithelial or mesothelial cells, and (3) cytologic
      preservation. The Giemsa-stained smear was used as a control for (1) and (2).
      Complete lysis of red blood cells was noted in the rehydration smears as compared
      with 70% red blood cell retention in the wet-fixed smears (P < .01). The
      rehydration smears retained 78% urothelial cells as compared with 55% in the wet
      fixed smears (P < .01). For ascitic and pleural fluid the cell retention did not
      differ significantly. The wet-fixed smears scored better for overall cytologic
      preservation, but the difference was not significant. The rehydration smears
      showed a decrease in the chromaticity of staining, more flattened cell clusters
      and slight cell enlargement. The rehydration method was beneficial for urine and
      blood-stained body cavity fluids.

PMID- 8291357
TI  - Primary melanoma of the cervix. A case report.
AB  - A case of malignant melanoma of the cervix was diagnosed on a Papanicolaou
      stained cervical smear from a 70-year-old women who had several small purpura
      like spots on the ectocervix at the time of a routine cervical examination. The
      smear was characterized by scattered, small, dissociated cells with
      hyperchromatic, irregular nuclei, prominent nucleoli and occasional cytoplasmic,
      brown pigment. The diagnosis was confirmed by subsequent cervical biopsy and
      radical hysterectomy.

PMID- 8291358
TI  - Cytomegalovirus-infected cells in a pleural effusion from an acquired
      immunodeficiency syndrome patient. A case report.
AB  - Cells with typical cytomegalovirus (CMV) inclusion bodies were found in smears of
      a pleural effusion from a 51-year-old acquired immunodeficiency syndrome patient.
      He suffered from severe, generalized CMV infection and Pneumocystis carinii
      pneumonia complicated by recurrent pneumothorax. CMV infection was proven by a
      positive immunohistochemical reaction. Cytologic demonstration of CMV-infected
      cells in a pleural effusion has not been reported before to the best of our
      knowledge.

PMID- 8291359
TI  - Fine needle aspiration of mammary carcinoma with features of a carcinoid tumor. A
      case report with immunohistochemical and ultrastructural studies.
AB  - We report a case of fine needle aspiration (FNA) of a mammary carcinoma with
      features of a carcinoid tumor from the right breast of an 87-year-old woman who
      had a history of a left mammary "carcinoid" tumor diagnosed histologically three
      years earlier. Aspiration cytology revealed extremely rich cellularity. The
      neoplastic cells were mostly dispersed; however, they also could be found in
      loose clusters, acinus-like formations and occasionally in small sheets. They
      were relatively small and regular and contained fairly uniform, mostly round and
      oval nuclei with moderately abundant cytoplasm. Many of the tumor cells had
      eccentric nuclei. Immunohistochemical study revealed that tumor cells from both
      the cytologic smear and histologic section were reactive with antibody against
      serotonin. Ultrastructural study performed on the simple right mastectomy
      specimen showed many membrane-bound, dense-core particles in the cytoplasm of
      neoplastic cells, consistent with neuroendocrine secretory granules.

PMID- 8291360
TI  - Primary adenoid cystic carcinoma of Bartholin's gland. A case report.
AB  - An extremely rare case of primary adenoid cystic carcinoma of Bartholin's gland
      in a 71-year-old woman is reported. With the working diagnosis of malignancy of
      Bartholin's gland on biopsy, she underwent a left radical vulvectomy with
      bilateral inguinal and pelvic lymphadenectomy and postoperative left vulvar
      irradiation. The cytologic and pathologic findings on the surgical specimens were
      distinctive. The imprint cytology of the cut surface of the tumor showed that the
      neoplastic cells were crowded and that some cells had a peripherally displaced
      nucleus. The nuclei were oval or round, and the quantity of chromatin was
      increased and fine. Some nuclei had prominent nucleoli. The cytoplasm was
      abundant. The surgical specimens showed the same findings as did cytology. the
      final diagnosis was primary adenoid cystic carcinoma of Bartholin's gland,
      postoperatively based on the cytologic and pathologic findings.

PMID- 8291361
TI  - Soft tissue chloroma diagnosed by fine needle aspiration cytology. A case report.
AB  - A case of soft tissue chloroma diagnosed by fine needle aspiration cytology is
      reported. The smears revealed numerous large, granular promyelocytes, rare
      eosinophils and metamyelocytes. The promyelocytes showed many Auer rods (faggot
      cells). The histologic sections of the excised tumor confirmed the cytologic
      diagnosis of chloroma. The patient developed leukemia seven months after excision
      of the chloroma.

PMID- 8291362
TI  - Cytologic diagnosis of neurocysticercosis. A case report.
AB  - We present a case of cerebral neurocysticercosis evaluated cytologically
      utilizing the "squash smear" technique. The parasite was very necrotic, and the
      smears contained numerous calcareous corpuscles only. These corpuscles were
      initially interpreted as psammoma bodies, quite consistent with the clinical and
      radiologic impression that the patient had a meningioma. However, on close
      examination, the corpuscles were recognized immediately as coming from a
      parasite. The cytologic differences between psammoma bodies and calcareous
      corpuscles are discussed. We also review briefly the nature of cysticercosis and
      its cytologic diagnosis.

PMID- 8291363
TI  - Atypia in fine needle aspiration cytology of nonpalpable and palpable
      mammographically detected breast lesions.
AB  - Widespread use of fine needle aspiration (FNA) in conjunction with mammography
      may lead to increased atypical or suspicious cytologic diagnoses. To assess the
      incidence and cytologic criteria of atypia in a mammographically screened
      population, we reviewed 220 FNA samples in this diagnostic category (5.8%
      incidence) from 3,798 FNAs performed in 1990-1991. The atypical category (134
      cases) included 72 benign and 62 malignant confirmed cases. Common benign
      diagnoses were fibroadenoma and fibrocystic changes (33 cases, or 46%). Features
      responsible for an atypical diagnosis in benign cases were increased cellularity,
      single epithelial cells and "reactive nuclear atypia," the last defined as a
      finely granular, uniform chromatin pattern with small, prominent nucleoli. The
      suspicious category included 86 cases; only 10 cases (12%) were confirmed benign
      lesions, and the remainder were malignant. These benign cases included 3
      fibroadenomas, 3 fibrocystic changes, 3 papillomas and 1 scar after radiotherapy.
      Two cases had prominent inflammation, a finding that should prompt caution.
      Malignant diagnoses in both categories included infiltrating and in situ cancers.
      A combination of limited cellularity, drying and/or bland nuclear features
      precluded a definitive diagnosis of cancer in many cases. For optimal management
      of mammographically screened patients, an acceptable "atypical" diagnostic rate
      should be defined for FNA. We conclude that a rate of less than 5% can be
      achieved by recognition of the following: (1) reactive atypia in the setting of
      fibrocystic and fibroadenomatous patterns, (2) significance of atypia in the
      setting of inflammation, and (3) improved sampling and sample preparation.

PMID- 8291364
TI  - Fine needle aspiration biopsy diagnosis of cysticercosis. A case report.
AB  - A case of cysticercosis was initially diagnosed by fine needle aspiration biopsy
      (FNAB). A tender, hard mass in a muscle was clinically suspected of being a
      benign tumor. An FNAB smear showed many eosinophils and a part of cestode. After
      10 minutes the patient felt a short-lived local hot sensation and pain. The
      diagnosis was confirmed on a histologic section of an incisional biopsy specimen
      from another site.

PMID- 8291365
TI  - Low grade mucoepidermoid carcinoma ex pleomorphic adenoma. A diagnostic problem
      in fine needle aspiration biopsy.
AB  - We report a case of low grade mucoepidermoid carcinoma arising in a pleomorphic
      adenoma (ex pleomorphic adenoma) in the parotid salivary gland of a 32-year-old
      woman. Fine needle aspiration biopsy showed the typical biphasic pattern of
      pleomorphic adenoma: groups of benign-appearing epithelial cells and
      chondromyxoid stroma. In addition, features of low grade mucoepidermoid carcinoma
      were identified retrospectively, consisting of background mucin and rare mucin
      containing cells. This case illustrates that the presence of background mucin and
      mucin-containing cells in an otherwise usual pleomorphic adenoma may indicate the
      presence of a well-differentiated mucoepidermoid carcinoma. In cases such as
      this, a definitive diagnosis should be postponed until the lesion is examined
      histologically.

PMID- 8291366
TI  - Fine needle aspiration cytology of congenital tracheal diverticulum. A case
      report.
AB  - The congenital tracheal malformation that gives rise to a cystic outpouching of
      the trachea is an uncommon entity that has received no attention in the cytologic
      literature. We report the clinical, cytologic and histologic findings in such a
      case.

PMID- 8291367
TI  - Benefit of prophylaxis by intravenous systemic vancomycin in granulocytopenic
      patients: a prospective, randomized trial among 59 patients.
AB  - We have tested the benefit of prophylaxis by intravenous systemic vancomycin
      among 59 neutropenic patients in a randomized trial. Vancomycin was delivered on
      day zero of chemotherapy until the resolution of neutropenia in the prophylactic
      group (vanco+). Empiric antibiotic therapy (piperacillin, ofloxacine) was
      identical for all patients. The number of days with fever > 38.5 degrees C was
      significantly higher in the control (vanco-) group than in the vanco+ group (7.4
      vs. 3.7, p < 0.02). Zero gram-positive infections occurred in the vanco+ group
      versus 9 in the vanco- group (p < 0.002). The mean number of days of empiric
      antibiotic therapy was reduced in the vanco+ group (11.3 vs. 16.3, p = 0.12).
      However, no benefit was noted between the two groups with regard to mortality or
      the severity of the infections. The selection of resistant microorganisms after
      systemic treatment with vancomycin is of potential risk. Such a prophylactic
      antibiotic regimen does not seem to be justified.

PMID- 8291368
TI  - Blood proteins C and S in sickle cell disease.
AB  - Proteins C and S are vitamin K-dependent proteins with an essential anti
      coagulant function. Protein C exists in an inactive form and is activated by a
      thrombin-thrombomodulin complex. Protein S combines with protein C and forms a
      stoichiometric complex which regulates coagulation in the presence of calcium. As
      patients with sickle cell disease (SCD) bear a high risk of developing thrombo
      embolic disorders, we studied the coagulation derangement in 100 patients and 40
      normal age- and sex-matched controls. The patients were clinically assessed and
      classified into sickle cell homozygotes (Hb SS), Hb S heterozygotes (Hb AS) and
      double heterozygotes for Hb S/beta 0-thalassaemia based on haematological
      parameters, red cell indices, Hb A2 and F levels and genetic studies. The
      proteins C and S were estimated and related to the type of the gene defect. The
      results showed significantly reduced levels of proteins C and S in SCD patients
      with the highest prevalence of deficiency in patients with a severe disease and
      frequent episodes of crisis. However, no significant differences were encountered
      in the level of proteins C and S in the same patients during the steady state and
      during episodes of crisis. It was concluded that the lower protein C and S levels
      in SCD is either due to decreased production or increased consumption though this
      reduction does not seem to play a role in producing thrombo-embolic disorders.

PMID- 8291369
TI  - Treatment of disseminated intravascular coagulation and its prodromal stage with
      gabaxate mesilate (FOY): a multi-center trial.
AB  - One hundred and ninety-one patients with disseminated intravascular coagulation
      syndrome (DIC) or its prodromal stage (preDIC) were treated with only gabaxate
      mesilate (FOY) (group G) or a combination of gabaxate and unfractionated heparin
      (group GH), and the efficacy of gabaxate was evaluated in a multicenter study.
      Following the treatment, the mean DIC score, which was evaluated on the basis of
      clinical symptoms and hemostatic parameters, decreased significantly to 5.58 +/-
      3.48 from 6.75 +/- 3.14 in group G (p < 0.001) and to 6.34 +/- 3.33 from 7.31 +/-
      3.00 in group GH (p < 0.05). In patients with overt DIC, the mean score decreased
      to 6.71 +/- 3.54 from 8.42 +/- 2.84 (p < 0.001). In DIC, the rate of overall
      efficacy was 46.2% in group G and 35.1% in group GH. In preDIC, it was 41.5% in
      group G and 27.3% in group GH. No side effects, including severe bleeding, were
      found in this study. The results indicate that gabaxate mesilate is clinically
      effective for patients with DIC and preDIC.

PMID- 8291370
TI  - Idiopathic thrombocytopenic purpura in Egyptian children.
AB  - 350 patients with idiopathic thrombocytopenic purpura (ITP) aged 2/12-15 years
      (mean 6.3 +/- 2.7) were followed up during the period January 1st, 1975 to March
      31, 1992. They constituted 40% of cases with hemorrhagic diathesis attending the
      Hematology/Oncology Clinic, Children's Hospital, Ain Shams University (relative
      frequency of 37.4/100.000 of the general Out-Patient Clinic in the same
      hospital). These patients presented with acute (71.4%), chronic (22.9%) and
      recurrent (5.7%) forms. The age of presentation was younger in acute ITP. In the
      recurrent form there was significant female predominance. Most cases of acute ITP
      (66%) presented in winter and spring, with a positive history of preceding viral
      illness in 50% in contrast to 10% in chronic form. Four chronic ITP cases
      developed lupus erythematosus; all were females > 9 years. As regards therapy,
      acute ITP cases with initial platelet count (PC) < 10 x 10(9)/l were randomized
      to receive either high-dose methyl prednisolone (HDMP) 10 mg/kg/day for 5 days
      i.v. (n = 10) or intravenous immunoglobulin (IVIG) 0.4 g/kg/day for 5 days (n =
      10) or conventional-dose prednisone (CDP) 2 mg/kg/day 4 weeks p.o. (n = 10). A
      dramatic response was noticed in the first two groups. In chronic ITP, (n = 80)
      CDP induced complete response (CR) in 30% and partial response (PR) in 20%; 50%
      were nonresponders. Twenty-four refractory ITP with persistent PC < or = 20 x
      10(9)/l received second-line therapy: vincristine 1.5 mg/m2/week i.v. 4 doses (n
      = 4) with no clinical or hematological improvement. IVIG 0.4 g/kg/day for 5 days
      (n = 8) with sustained CR only in 2 patients (25%) and PR in 2 patients (25%).
      Splenectomy was performed (n = 12) with CR in 50%; out of them, 2 patients had
      shown no improvement on prior IVIG therapy. In conclusion, ITP is a benign
      condition with no fatality reported, but it could run a chronic refractory
      course.

PMID- 8291371
TI  - Secondary hypoplastic anemia in patients with familial amyloidotic
      polyneuropathy.
AB  - The anemia of patients with familial amyloidotic polyneuropathy (FAP) was
      evaluated. Anemia was seen in 32 (91%) of the 35 FAP patients, more often with
      progression of the disease. The incidence of macrocytic hypochromic anemia was
      the most common type (40%). In 14 autopsied and 2 biopsied cases, no amyloid
      deposition was detected in the bone marrow. Thirteen (81%) of the 16 FAP patients
      showed hypoplastic bone marrow. Bone marrow aspiration of 2 patients revealed a
      decreased ratio of erythrocytic/myelocytic cells. The plasma levels of vitamin
      B12 and folate were within normal ranges. Neither oral nor intravenous
      administration of iron had any effect on the anemia of FAP patients. Intravenous
      erythropoietin elevated blood hemoglobin levels and blood pressure in 2 patients.
      Orthostatic hypotension, one of the most common symptoms of FAP, was unexpectedly
      improved. Secondary hypoplastic anemia is common in FAP, but treatment of anemia
      in this disease using erythropoietin is promising.

PMID- 8291372
TI  - Urinary magnesium excretion in steady-state sickle cell anaemia.
AB  - Previous reports indicate that individuals with sickle cell anaemia may be
      magnesium deficient. The role of renal excretion of magnesium in the pathogenesis
      of this low magnesium status was investigated in 25 patients with sickle cell
      anaemia (sicklers) in the steady state and in 25 age- and sex-matched controls
      with haemoglobin genotype AA. The clearance, excretion fraction and excretion
      rates of magnesium were enhanced in the sicklers. These patients also had
      significantly lower erythrocyte and plasma magnesium concentrations than the
      controls. However expressed, urinary magnesium showed a significant positive
      correlation with plasma magnesium and a weak negative correlation with
      erythrocyte magnesium. Furthermore, a significant negative correlation was
      observed between erythrocyte and plasma magnesium in the sicklers. These results
      suggest that urinary disposal of magnesium in rates and amounts inappropriate to
      the body stores of the cation may be one of the mechanisms accounting for
      hypomagnesaemia and low erythrocyte magnesium content in patients with sickle
      cell anaemia.

PMID- 8291373
TI  - Failure to detect spindle-shaped fibroblastoid cell progenitors in PBPC
      collections.
AB  - We assessed the development of an adherent stromal layer in peripheral blood
      progenitor cells (PBPC) collections of 17 patients with solid tumors and
      hematological malignancies (n = 38), as well as in normal and disease-free bone
      marrow samples (n = 14). Light-density mononuclear cells from peripheral blood
      leukapheresis maintained in long term culture (LTC) conditions for at least 3
      weeks failed to develop a stromal layer as was observed in all bone marrow
      samples. We found no differences with regard to CFU-GM growth, CD34+ percentage
      or cytological morphology. Our results indicate that spindle-shaped fibroblastoid
      cell progenitors present in the bone marrow are not mobilized towards peripheral
      blood by chemotherapy and/or growth factor stimulation, contrasting with
      hematopoietic progenitors, which, as is well known, are able to circulate. The
      absence of stromal progenitors in PBPC autografts does not appear to be relevant
      for a successful hematopoietic engraftment.

PMID- 8291374
TI  - GM-CSF and eosinophil chemotactic factors in an acute lymphoblastic leukemia
      patient with eosinophilia.
AB  - We describe a patient with common acute lymphoblastic leukemia associated with
      blood and cerebrospinal fluid (CSF) eosinophilia. Serum obtained at onset and
      conditioned medium prepared from T cells obtained at remission stimulated with
      interleukin-2 contained eosinophil colony stimulating activity (Eo-CSA), which
      was confirmed to be predominantly GM-CSF. Leukemic cell conditioned medium and
      serum obtained at remission contained no Eo-CSA. The CSF contained increased
      eosinophil chemotactic activity, however, this factor was not identified.

PMID- 8291375
TI  - Ph+ acute myelogenous leukemia with t(7;11)(p15;p15) and clonal evolution in
      relapse after bone marrow transplantation.
AB  - A 20-year-old female with Ph+ acute myelogenous leukemia (M2) associated with
      t(7;11)(p15;p15) is reported. Bone marrow aspirates were hypercellular with
      leukemic cells including Auer rods. Chromosome analysis showed t(7;11) and the Ph
      chromosome. After complete remission, normal karyotype was restored. Normal male
      karyotypic cells replaced the bone marrow following allogeneic bone marrow
      transplantation from her brother. On day 358, cytogenetic study at relapse
      revealed 14q+ as an additional change and clearly showed that the abnormal clone
      was derived from the patient, because metaphases with XX were all of abnormal
      karyotype and those with XY were normal.

PMID- 8291376
TI  - Acquired antithrombin III deficiency: replacement with antithrombin III
      concentrates in a patient with protein S deficiency accelerates response to
      therapy.
AB  - A 33-year-old man with inherited protein S deficiency and a 20-year history of
      deep and superficial venous thrombosis was admitted for treatment of extensive,
      acute, superficial venous thrombosis of the left lower extremity. Clinical
      response to intravenous heparin was very slow. After discovery of acquired
      antithrombin III deficiency superimposed on the protein S deficiency, he was
      given antithrombin III concentrates with the intravenous heparin. His response to
      therapy was accelerated. The development of acquired antithrombin III deficiency
      in patients with venous thrombosis may slow the response to standard
      anticoagulant therapy. Therapy of the thrombosis may be improved with
      administration of antithrombin III concentrates.

PMID- 8291377
TI  - Interstitial pneumonitis possibly due to mitoxantrone.
AB  - A 41-year-old patient with chronic myelogenous leukemia in the accelerated phase
      was treated with mitoxantrone. She developed pyrexia 7 days after receiving the
      third administration of mitoxantrone. After 3 more days, she experienced dry
      cough and dyspnea. Bilateral fine crackles were audible, but no signs of heart
      failure were found. A chest X-ray film revealed diffuse reticulogranular
      infiltrates bilaterally. An increase in the prednisolone dosage led to an
      improvement. Specimens of the bronchoalveolar lavage revealed an increase in CD4
      /CD8- lymphocytes. The peripheral lymphocytes also expressed neither CD4 nor CD8.
      Specimens of a transbronchial lung biopsy disclosed thickening of the alveolar
      wall with infiltration of lymphoid cells.

PMID- 8291378
TI  - Multiple recurrence of acute idiopathic thrombocytopenic purpura.

PMID- 8291379
TI  - Hypereosinophilic syndrome terminating in acute myelogenous leukemia.

PMID- 8291380
TI  - Epidural and intrathecal analgesia.

PMID- 8291381
TI  - Always read the label.

PMID- 8291382
TI  - Medicare rural hospital pass-through for CRNA services.

PMID- 8291383
TI  - Nurse anesthesiology faculty: what is your commitment?
AB  - Faculty workload determination formulas are a means by which program directors
      can justify their time and that of other faculty. This article is written to
      assist faculty in this necessary yet time-consuming endeavor. A table of
      calculations (time/activity ratio) for determination of committed hours, examples
      of actual workload determination, and a worksheet are provided.

PMID- 8291384
TI  - American Association of Nurse Anesthetists latex allergy protocol.

PMID- 8291385
TI  - The law and the AIDS-infected healthcare worker.

PMID- 8291386
TI  - A biting commentary on monitored anesthesia care with conscious sedation.
AB  - In summary, a continued emphasis needs to be placed on better operationalization
      of the concept of MAC and its components, not merely for reimbursement, but for
      practice sake. Quality risk evaluation and patient assessment guidelines unique
      to MAC and conscious sedation need to be established and closely adhered to. In
      1988, the AANA Board of Directors adopted suggested guidelines for registered
      professional nurses engaged in the administration of intravenous conscious
      sedation. These guidelines were an addendum to Position Statement 2.2 entitled
      "Qualified Providers of Conscious Sedation" and are found in the Professional
      Practice Manual for the Certified Registered Nurse Anesthetist. It is incumbent
      upon all CRNAs who provide such services to not only be familiar with but also
      practice in accordance with these guidelines. Finally, as HCFA directs each
      Medicare carrier to determine when MAC is the appropriate standard of care, we as
      providers must recognize the same. Within each case scheduled under MAC lies the
      challenge to provide and maintain a high degree of vigilance in perhaps the more
      minor surgical procedure, while always anticipating and recognizing the potential
      for the unexpected that can make it hard for any professional to swallow.

PMID- 8291387
TI  - Council on Certification Professional Practice Analysis.
AB  - The CCNA has completed a PPA and will begin implementing its recommendations with
      the December 1993 certification examination. The results of the PPA provide
      content validation for the CCNA certification examination. The certification
      examination is reflective of the knowledge and skill required for entry-level
      practice. Assessment of this knowledge is accomplished through the use of
      questions that are based on the areas represented in the content outline.
      Analysis of the PPA has resulted in changes in the examination content outline
      and percentages of questions in each area to reflect current entry-level nurse
      anesthesia practice. The new outline is based on the major domains of knowledge
      required for nurse anesthesia practice. These changes are justified by the
      consistency in the responses of the practitioners surveyed. There was overall
      agreement as to the knowledge and skills related to patient conditions,
      procedures, agents, techniques, and equipment that an entry-level CRNA must have
      to practice. Members of the CCNA and Examination Committee will use the revised
      outline to develop questions for the certification examination. The questions
      will be focused on the areas identified as requiring high levels of expertise and
      those that appeared higher in frequency. The PPA survey will be used as a basis
      for subsequent content validation studies. It will be revised to reflect new
      knowledge, technology, and techniques related to nurse anesthesia practice. The
      CCNA has demonstrated its commitment to the certification process through
      completion of the PPA and implementation of changes in the structure of the
      examination.

PMID- 8291388
TI  - Sedation by infusion: a clinical trial in cardiac surgery patients.
AB  - The problem of sedation and analgesia for ventilator-dependent patients was
      examined in this study. Twenty subjects undergoing elective coronary
      revascularization surgery at a major medical center were studied. They ranged in
      age from 49 to 83 years. A randomized, prospective research design was used to
      place subjects in either an experimental group or a control group. Standard
      postoperative analgesia with intravenous increments of morphine and midazolam in
      the control group was compared to treatment with a titratable sufentanil
      midazolam infusion in the experimental group. In both groups, hemodynamic
      variables were measured at selected intervals, sodium nitroprusside consumption
      was measured, and time to extubation was noted. Data analysis demonstrated no
      statistically significant differences between the experimental and control
      groups. The more costly sedative-analgesic infusion appeared to be comparable to
      conventional treatment with incremental morphine and midazolam based on the
      results of this study.

PMID- 8291389
TI  - Anesthetic management of a patient with moyamoya disease: a case report.
AB  - A previously healthy 4-year-old female presented with an 18-month history of
      frequent headaches and seizures. Magnetic resonance imaging (MRI) and angiography
      revealed severe stenosis of the left proximal intracranial carotid artery, with
      bilateral development of moyamoya vessels, left greater than right. A diagnosis
      of moyamoya disease was made, and the patient was scheduled for surgical
      correction consisting of an encephalo-duro-arterio-synangiosis. Moyamoya disease
      is a rare, occlusive cerebrovascular disorder characterized by bilateral stenosis
      of the internal carotid arteries and their branches. While its etiology is
      currently uncertain, recent studies indicate that focal arteritis, secondary to
      an antigen-antibody reaction, leads to the development of the stenosis.
      Anesthetic management of patients with moyamoya disease focuses on maintenance of
      adequate cerebral blood flow, normalization of intracranial pressure, and
      avoidance of both cerebral vasoconstriction and vasodilation. Several anesthetic
      techniques have been successfully employed; one such method is presented.

PMID- 8291390
TI  - Anesthetic management of cerebral aneurysm clipping during pregnancy: a case
      report.
AB  - A 35-week pregnant female presented emergently for clipping of a cerebral
      aneurysm under general anesthesia. The patient was neurologically stable with an
      active fetus. Anesthetic goals for this patient included maintenance of
      uteroplacental perfusion, fetal well-being, and maternal well-being. Maternal
      monitoring consisted of invasive arterial blood pressure, central venous
      pressure, and urine output, in addition to the standard monitors for anesthesia.
      Fetal monitoring consisted of fetal heart rate by external Doppler and uterine
      activity by external tocometer. Anesthesia care was directed at ensuring optimal
      maternal and fetal well-being. The aneurysm was clipped, and the patient emerged
      from anesthesia without neurological deficits. No uterine activity was noted
      intraoperatively. Fetal heart rate was maintained between 125 and 160 beats per
      minute. A healthy baby was delivered 11 days postoperatively by cesarean section
      under regional anesthesia. The Apgar score was 8/9 at 1 and 5 minutes.

PMID- 8291391
TI  - A method of evaluating efficiency in the operating room.
AB  - A scientific four-step approach to evaluating efficiency in the operating room
      (OR) is described. These steps include identification of sequential work
      activities (SWAs) that are critical to the timely progression of surgical cases
      through the OR, identification of a time standard for completion of SWAs, direct
      observations of the amount of time required for completion of SWAs, and analysis
      of results. Two strategies to improve OR efficiency are described. Intergroup
      strategies require coordination of work among various specialty groups involved
      with the progress of cases through the OR. Interpersonal strategies necessitate
      coordination of work between two or more people within the same specialty group.

PMID- 8291392
TI  - Anesthesia for the homeless.
AB  - Healthcare for the homeless is often crisis-oriented and fragmented. Homelessness
      may be associated with ongoing healthcare problems such as tuberculosis, human
      immunodeficiency virus (HIV), acquired immune deficiency syndrome (AIDS), and
      substance abuse. The purpose of this study was to identify the anesthesia
      services required by homeless individuals from an urban area. The anesthesia
      records of all individuals (N = 40) identified as being homeless and receiving
      care at one New York City medical center during a 12-month period were reviewed.
      Approximately one-half (47.5%) of the 40 patients in the study did not require
      general anesthesia but intubation only. Most of these intubations were for
      cardiac/respiratory arrests of unknown cause, drug/alcohol overdose, or multiple
      trauma. Of the 21 patients requiring surgery, 15 had emergency procedures such as
      splenectomy, appendectomy, exploratory laparotomy, incarcerated hernia repair,
      and reduction of fractures. The findings of this study support previous research
      which indicates that most homeless people enter into care for emergency rather
      than elective services.

PMID- 8291393
TI  - AANA Journal course: update for nurse anesthetists--anesthetic techniques for
      patients with valvular heart disease presenting for noncardiac procedures.
AB  - Providing anesthesia for patients with valvular heart disease undergoing
      noncardiac surgery can be extraordinarily challenging. Not only must the
      principles of normal cardiac physiology be mastered, but also those of the
      pathophysiology associated with the various valvular lesions. This course will
      provide a review of the pathophysiology and specific compensatory mechanisms for
      aortic stenosis, aortic insufficiency, mitral stenosis, and mitral regurgitation.
      Characteristic findings in the patient interview, physical examination, and
      diagnostic studies will be discussed. Anesthetic and monitoring considerations
      pertinent to each valvular lesion will be offered.

PMID- 8291394
TI  - Practice issues: overview of federal agencies.

PMID- 8291395
TI  - Cardiopulmonary resuscitation: updates, outcomes, and the need for critical
      comparisons.

PMID- 8291396
TI  - Cardiopulmonary resuscitation standards: the 1992 Dartmouth experience in review.

PMID- 8291397
TI  - Drug Enforcement Administration mid-level practitioner regulation.

PMID- 8291398
TI  - Budget Reconciliation Law contains single anesthesia fee cuts.
AB  - While OBRA93 will result in payment reductions for CRNAs and anesthesiologists
      involved in the anesthesia care team, the law also contained AANA victories.
      First, the anesthesia care team reductions will be phased in over several years
      rather than occurring immediately in 1994. Second, RAP DRGs were defeated. Third,
      the use of actual anesthesia time for purposes of Medicare billing was retained.
      Fourth, parity in payments for new physicians/new CRNAs was restored. Fifth,
      teaching anesthesiologists will receive the same payment for supervising two
      anesthesiologist residents as they do for working with two nurse anesthesia
      students beginning in 1994. The AANA concerns that were not addressed on OBRA93,
      such as the TEFRA conditions and access to clinical privileges, are not dead.
      They will be lobbied for again in future legislative vehicles, such as President
      Clinton's healthcare reform plan.

PMID- 8291399
TI  - Should student nurse anesthetists be required to administer regional anesthesia?
AB  - Although millions of anesthetics are administered by Certified Registered Nurse
      Anesthetists (CRNAs) every year, all CRNAs are not trained in the actual
      administration of regional anesthesia. Some individuals believe that all students
      should receive this instruction while enrolled in nurse anesthesia education
      programs. This belief has resulted in the Council on Accreditation of Nurse
      Anesthesia Educational Programs being encouraged to adopt an accreditation
      requirement for the administration of regional anesthesia by students. Clinical
      experience in administration would supplement experience in managing regional
      anesthetics and didactic instruction that students do receive. This study
      identified the current practices in nurse anesthesia programs related to the
      administration of regional anesthesia by students and reasons for supporting or
      opposing an accreditation requirement.

PMID- 8291400
TI  - AANA Journal course: update for nurse anesthetists--cardiac pacemakers.
AB  - Pacemakers are commonly encountered in our care of patients. It is essential for
      clinicians to have some understanding of indications for perioperative pacing;
      the function, design, and classification of the different types of pacemakers;
      and the clinical problems which may be encountered when caring for patients who
      have pacemakers. This installment of the AANA Journal Course addresses these
      issues.

PMID- 8291401
TI  - Evaluation of a nasal/oral discriminate sampling system for capnographic
      respiratory monitoring.
AB  - Although continuous end-tidal carbon dioxide (PETCO2 mmHg) measurements permit
      the earliest detection of alveolar hypoventilation, apnea and/or obstruction,
      technical difficulties have thus far precluded its reliable implementation in the
      spontaneously breathing patient with a natural (e.g., nonartificially secured)
      airway. Among the technical difficulties is the fact that conventional sampling
      devices do not take into account the possibility that breathing may take place
      primarily through either the nose or the mouth. As a result, the efficacy of a
      new nasal/oral discriminate sampling system (NODSS) was examined for capnographic
      observation of respiratory adequacy. NODSS is unique because it provides the
      opportunity to select simultaneous or discriminate collection of carbon dioxide
      exhaled through the nose and/or mouth. Twenty-four American Society of
      Anesthesiologists physical status I to IV patients (ages 30-88 years) were
      capnographically monitored in the postanesthesia care unit following general
      anesthesia for various surgical procedures. All patients were extubated and
      breathing spontaneously. Simultaneously, direct arterial carbon dioxide (PaCO2
      mmHg) determinations were made using an indwelling radial artery catheter to
      determine their correlation with PETCO2 obtained by NODSS. A comparison between
      PaCO2 values and noninvasive nasal and/or oral PETCO2 obtained by NODSS showed a
      positive correlation (r value) of 0.602 to 0.849 when statistically analyzed by
      Pearson's product-moment correlation coefficient. There was no significant
      difference between the mean (PaCO2-PETCO2) gradient derived through nasal
      sampling, as compared to the mean gradient derived by oral sampling with this
      device (P > 0.05). Noninvasive capnographic monitoring by NODSS is a convenient,
      reliable, effective, and accurate alternative to direct arterial blood gas
      determination that may be used for the early detection of respiratory inadequacy
      in the spontaneously breathing patient who has a natural airway.

PMID- 8291402
TI  - Adenosine treatment of supraventricular tachycardia following epidural test dose:
      a case study.
AB  - This is a case report of supraventricular tachycardia following initiation of
      epidural analgesia with use of an epinephrine test dose in a parturient during
      active labor. Vagal stimulatory efforts failed to interrupt the arrhythmia, but
      treatment with adenosine was successful. Fetal monitoring with a scalp electrode
      provided evidence of fetal well-being throughout the episode. Adenosine was
      chosen because of its safety for both the mother and the fetus and its lack of
      the hypotensive effect often seen with verapamil.

PMID- 8291403
TI  - Cementless total hip replacement. Bio-active glass ceramic coating studied in
      dogs.
AB  - We studied 2 types of a cementless total hip prosthesis in dogs. Both were coated
      with titanium plasma-spray. In both components, the pores in the deep layer of 1
      group were further coated with apatite and wollastonite containing glass-ceramic
      (AW glass-ceramic). 50 dogs underwent unilateral total hip replacements, and were
      killed at 1, 3, or 6 months postoperatively. We evaluated the femoral and the
      acetabular components mechanically and histologically. At 1 month, the detaching
      load and bone ingrowth of the AW glass-ceramic-coated femoral and acetabular
      components were higher than those of the control implants. At 3 and 6 months
      there were no differences between the 2 types of components. Thus, AW glass
      ceramic enhanced the early phase of cementless implant fixation.

PMID- 8291404
TI  - High cathepsin B activity in arthroplasty interface membranes. A histochemical
      study of 9 loose cemented total hip prostheses.
AB  - We studied biopsies of interface membranes of 9 aseptically loosened total hip
      prostheses. The morphologic resemblance of the cement-facing surface of the
      membranes to synovial tissue of arthritic joints, as noticed by others, was
      confirmed by histochemical techniques. High cathepsin B activity was found in the
      bone-facing surface of the membranes. Since this enzyme also plays an important
      role in tissue destruction of arthritic joints, further similarities in the
      mechanisms of tissue breakdown in arthritis and aseptic loosening of cemented hip
      prostheses may be conjectured.

PMID- 8291405
TI  - Histology of porous-coated acetabular components. 25 cementless cups retrieved
      after arthroplasty.
AB  - 25 hemispherical acetabular components retrieved from patients who had a total
      hip arthroplasty (THA) were studied histologically. All of the components had
      titanium fiber metal porous coatings and were implanted with adjuvant screw
      fixation, 18 in primary THA and 7 in revision THA. None of the cups had been
      removed because of infection or failure of fixation. The components had been in
      place an average of 30 (1-140) weeks. 18 cups had bone ingrowth into the porous
      coating. Up to one third of the available void space within the porous coating
      was occupied by bone, while the maximal proportion of the area of the bone
      implant interface with bone ingrowth was over 80 percent. Bone ingrowth was more
      often observed at the dome and in the vicinity of sites of screw fixation than
      elsewhere. Peripherally, bone ingrowth was less consistent, and in isolated areas
      fibrocartilage and mineralized fibrocartilage were occasionally observed. The
      longer-term cases had more bone ingrowth than the shorter-term cases. Apparent
      metallic debris was observed within histiocytes adjacent to screw holes, and the
      amount of this material increased with duration of implantation.

PMID- 8291406
TI  - Cement particles inhibit bone growth into titanium chambers implanted in the
      rabbit.
AB  - Particles of bone cement have been shown previously to stimulate the resorption
      of bone. The purpose of this study was to determine whether particles of bone
      cement (BC) have an adverse effect on bone ingrowth. The bone harvest chamber was
      implanted bilaterally in the proximal tibial metaphysis of 6 mature rabbits. Both
      the fixed outer cylinder and the inner removable core of the chamber have a
      transverse 1 mm wide pore providing a continuous canal for tissue ingrowth. After
      an initial 6-week period for osseointegration of the outer cylinder, the contents
      of the inner core were harvested repeatedly at 3 weekly intervals. In the first
      series of rabbits, the carrier solution, 1% sodium hyaluronate (Healon) was
      implanted first. In subsequent implantations, Healon was mixed with small
      fabricated particles of BC (averaging 3.54 mm in diameter) to fill the channel of
      the core. The contralateral chamber was left empty and served as a control. In
      the second series of rabbits, implantation was carried out sequentially using the
      same material bilaterally. The sections from the control harvests, and those with
      Healon alone contained extensive trabecular bone arranged longitudinally in the
      canal, in a fibrovascular stroma. The sections containing BC particles were
      infiltrated by foamy, mononuclear and multinuclear histiocytic cells. Less
      trabecular bone was seen in the sections containing BC particles compared to the
      control sections or those containing Healon alone. Previous studies have shown
      that particles of bone cement stimulate bone resorption. In this study, BC
      particles have also been shown to diminish the formation of new bone.

PMID- 8291407
TI  - Noncollagenous proteins in heterotopic ossification. Immunohistochemical analysis
      in 15 paraplegies.
AB  - We used immunohistochemical techniques to investigate the distribution pattern of
      osteonectin, osteocalcin, bone sialoprotein II and the small proteoglycans
      decorin and PG 100 during different stages of heterotopic ossification (HO) in
      pressure sores of paraplegic patients. All these noncollagenous proteins (NCPs)
      accumulated in fibroblasts and preosteoblasts, predominantly in the activity
      centers of early osteogenetic areas. Mature types of HO showed a more discrete
      expression pattern for this protein group, with weaker reactions in the narrow
      osteoblastic rims. Decorin was detected predominantly in the stroma of HO. Our
      results indicate that the NCPs are important components during the pathogenesis
      of HO and that fibroblasts may serve as osteoprogenitor cells.

PMID- 8291408
TI  - Indomethacin for prevention of heterotopic ossification. A randomized controlled
      study in 41 hip arthroplasties.
AB  - The effect of indomethacin 25 mg 3 times daily during the first 2 postoperative
      weeks in preventing heterotopic bone formation after cemented total hip
      arthroplasty was investigated in a randomized, double-blind and placebo
      controlled clinical trial on 57 patients. 16 patients were secondarily excluded,
      leaving 19 patients in the indomethacin group and 22 patients in the placebo
      group. Evaluated from the 3-month radiographs, 18/19 indomethacin patients
      developed either no or only the milder Grade 1 ossification. In contrast, 11/22
      placebo patients developed Grade 2 or 3 ossifications. Our observations favor
      indomethacin prophylaxis for 2 weeks in cemented arthroplasty of the hip.

PMID- 8291409
TI  - Airport metal detectors and orthopedic implants. The responses of arch and hand
      held devices.
AB  - 8 subjects with a variety of orthopedic implants were examined by the security
      staff at an international airport using arch and hand-held metal detectors. None
      of the subjects caused activation of the alarm on the arch, although the presence
      of metal was registered in 2 at a level below the alarm threshold. The hand-held
      detectors alarmed over the larger superficial implants. A substantial tissue
      screening effect was noted.

PMID- 8291410
TI  - Function 10 years after hip fracture. 74 patients after internal fixation.
AB  - We examined the physical and social function of patients surviving 10 years after
      internal fixation of a hip fracture. 74 out of 362 patients were alive 10 years
      after their fracture. In 47 survivors after cervical fracture, secondary hip
      arthroplasties had been performed in 25, and nails had been extracted in 13. The
      implants had been removed in 8 of 27 with trochanteric fracture. 58 survivors
      were interviewed; three fourths were still living in their own homes, with more
      than half needing no home assistance. However, limitation of activities, caused
      by the fracture, was experienced by more than one third of the survivors.

PMID- 8291411
TI  - Effect of sex and age on the ratio of cervical to trochanteric hip fracture. A
      meta-analysis of 16 reports on 36,451 cases.
AB  - We analyzed 15 published reports and our own data. In women, the ratio of
      cervical to trochanteric fractures (C/T) evolved in 3 periods. 1) Before the age
      of 50 years, the annual incidence of cervical fracture is close to that of
      trochanteric fracture. 2) Between 50 and 60 years, cervical fracture increases
      markedly, and the C/T ratio is well above unity at an age when the fracture
      incidence is still very low. 3) This imbalance progressively diminishes to reach
      unity in the very old, as the result of a progressive increase in trochanteric
      fractures. In men, cervical fractures are progressively more common with
      increasing age, and the C/T ratio exceeds unity after 70 years of age. In both
      genders, the incidence of cervical fracture is thus greater than that of
      trochanteric fracture during a limited period of time, in the perimenopausal
      period for women and in elderly men. Several hypotheses on the mechanics of falls
      and bone strength have been advanced, without any satisfactory explanation for
      the C/T sex and age changes.

PMID- 8291412
TI  - Surgery for chronic symptoms after whiplash injury. Follow-up of 20 cases.
AB  - 20 patients operated on with discectomy and anterior cervical fusion because of
      chronic symptoms after whiplash injury were examined 4 years after surgery. The
      commonest indications for surgery were disabling headache and neck pain and
      radiographically verified disc protrusion. At follow-up, 11 patients had reduced
      headache and neck pain, while paresthesia and radicular pain were diminished in 9
      patients. Based on Robinsson's criteria for the evaluation of surgical results, 2
      patients had good, 9 had fair and 9 had poor results.

PMID- 8291413
TI  - Kinematic and stability of the Norway elbow. A cadaveric study.
AB  - We investigated the effect of simulated muscle loading and the contribution of
      the radial head to stability of the Norway elbow in 6 cadavers using an
      electromagnetic tracking device. The kinematics of the elbow after implantation
      of the prosthesis were similar to the intact elbow in their valgus-varus
      orientation, however, the forearms were slightly externally rotated, probably due
      to a small amount of external rotation of the humeral components at the time of
      implantation. The valgus-varus laxity limit of the implants were greater than in
      the intact specimens averaging 8.0 and 5.6 degrees, respectively. Simulated
      muscle loading stabilized both the intact and the Norway elbows. Excision of the
      radial head after implant arthroplasty increased their valgus-varus laxity,
      suggesting that preservation of the radial head may be indicated if it is not too
      severely involved by the underlying disease process. The laxity permitted by the
      prosthesis articulation is greater than that measured after implantation of the
      Norway arthroplasty. This suggests that the prosthesis may behave as an
      unconstrained arthroplasty. This should minimize the stress experienced by the
      bone-cement interface and may reduce the incidence of loosening. The laxity of
      the elbows after joint arthroplasty were only slightly greater than normal,
      possibly explaining the low incidence of prosthesis dislocation which has been
      observed with clinical use.

PMID- 8291414
TI  - External compression of forearm nonunion. A report on 6 cases.
AB  - We treated 6 patients with 7 cases of aseptic nonunion of the forearm with
      external fixation and compression (Orthofix) without open reduction and bone
      grafting. By turning a screw on the side of the bar, compression was carried out
      until the nonunion gap with radiographically obliterated, usually within 2 weeks.
      After compression had stopped, the external fixator was retained during the
      following period of healing and bone remodeling. Healing of the nonunions was
      seen after 7 (4-11) weeks. 5 patients obtained normal mobility, while 1 had
      slightly restricted supination and pronation.

PMID- 8291415
TI  - Percutaneous autogenous bone marrow grafting in 20 cases of ununited fracture.
AB  - We grafted autogenous bone marrow percutaneously to stimulate healing in 20
      ununited long bone fractures. 15-20 mL of bone marrow was injected twice, with an
      interval of 3 weeks. All cases were immobilized in a plaster cast. 17 cases
      united in 5 (3-7) months.

PMID- 8291416
TI  - Knee function after operation for malignancy of the distal femur. Quadriceps
      muscle mass and knee extension strength in 21 patients with hinged
      endoprostheses.
AB  - We evaluated quadriceps muscle mass and knee extension strength in 21 patients
      after resection and endoprosthetic replacement of the distal femur for malignant
      bone tumor. In all cases, a modular cementless, hinged prosthesis had been used.
      The mean follow-up period was 4 (2-9) years. Muscle mass was measured
      ultrasonographically, and strength isokinetically with a Cybex 6000 dynamometer.
      All the data for the operated side are given as percentage of the non-operated
      side. The average quadriceps mass was 48 (27-70) percent. The average peak torque
      was 31 (14-48) and 36 (18-55) percent at the speed of 30 degrees/s and 90
      degrees/s, respectively. The reduction in extension strength became greater with
      increasing flexion. There was a moderate correlation between muscle mass and
      muscle strength. Most of the patients who had kept more than 40 percent of the
      quadriceps mass had more than 30 percent peak torque. Patients with excellent
      function (Enneking 1987) had more quadriceps muscle mass and higher strength than
      those that were merely good with the borderline at about 40 percent muscle mass.

PMID- 8291417
TI  - Bioactive glass versus hydroxylapatite in reconstruction of osteochondral defects
      in the rabbit.
AB  - We studied osseointegration of a bioactive glass (BG) and hydroxylapatite (HA) in
      rabbit femur epiphyseal and metaphyseal regions. 17 BG and 24 HA cones implanted
      in defects through arthrotomy were analyzed. The holes for implants were drilled
      through distal femur joint surfaces. The cartilage wound repaired generally by
      fibrous tissue. Histomorphometry showed that 61, 78, and 79 percent of BG surface
      was covered by bone at 3, 6, and 12 weeks, respectively. The corresponding
      figures for HA were 47, 67, and 78 percent. Chemical bonding between bone and
      implants of both types was confirmed by scanning electron microscopy (SEM) and
      energy-dispersive x-ray analysis (EDXA). Formation of a calcium phosphate-rich
      layer on the surface BG implant was demonstrated by EDXA. Our results indicate
      that the osseointegration rate of bioactive glass does not differ from that of
      hydroxylapatite.

PMID- 8291418
TI  - Effect of tibial lengthening on the gastrocnemius muscle. A histopathologic and
      morphometric study in rabbits.
AB  - We observed the changes of the gastrocnemius muscle in relation to the percentage
      of lengthening of the rabbit's tibia by callotasis. 75 rabbits were separated
      into 3 lengthening groups, 10, 20, and 30 percent lengthening, respectively.
      Histopathologic observations, based on the fiber size variation, internalization
      of the nuclei, degeneration, regeneration, and endomysial fibrosis of muscle
      fibers, revealed that substantial changes occurred in the latter groups.
      Histomorphometrically, the decrease in the mean size of Types I and II muscle
      fibers was observed in all lengthening groups, but there was no significant
      change in the proportion of the muscle fiber types in any of the lengthening
      groups.

PMID- 8291419
TI  - Observer variation in the Lauge-Hansen classification of ankle fractures.
      Precision improved by instruction.
AB  - We investigated whether instruction can decrease the variation in the
      classification of ankle fractures. The radiographs of 100 consecutive ankle
      fractures were twice assessed by 8 observers, using the Lauge-Hansen
      classification system. 1 group of 4 observers was given special instruction
      between 2 assessments. Without instruction the interobserver variation was
      identical at the first and second assessments. After instruction, the agreement
      increased from 0.66 to 0.75. These results show that the variation in the Lauge
      Hansen classification system can be reduced by instruction.

PMID- 8291421
TI  - Failed innovation in total hip replacement. Diagnosis and proposals for a cure.
AB  - Many new hip prosthesis and fixation techniques have been introduced in
      orthopedics in recent years. Yet, none have provided superior total hip
      replacements (THR) in comparison to the traditional cemented Charnley concept,
      which nevertheless has limited long-term endurance. This review article
      investigates why the THR innovation process has failed. The predominant causes
      for long-term failure of THR are discussed. A framework of generic failure
      scenarios is proposed to provide guidelines for a scientifically-oriented
      approach to THR design, testing and clinical evaluation. It is shown that THR
      components are subject to incompatible design goals as regards prevention of the
      different failure scenarios. Neglect of those has been one important factor in
      the present innovation impasse. A second factor is the trial-and-error culture in
      orthopedic surgery, in which new devices run through the innovation cycle without
      proper testing or rigorous postoperative analysis. The third factor is
      ineffective regulation of marketing approval with respect to orthopedic implants.
      Scientific research in orthopedics and related sciences has produced new methods
      for systematic design evaluation, pre-clinical testing and clinical trials. These
      can provide a basis for self-regulation and self-control by the orthopedic
      community, in all stages of the innovation process.

PMID- 8291420
TI  - Candida albicans arthritis in a nonimmunocompromised patient. Complication of
      placebo intraarticular injections.
AB  - A nonimmunocompromised 32-year-old man with arthrosis of the knee participated as
      a placebo control in a clinical trial of intraarticular injections of hyaluronan.
      After the fourth weekly injection of saline, he developed a warm and swollen
      knee, and synovial fluid cultures revealed growth of Candida albicans. Oral
      fluconazole treatment was instituted 2 weeks after onset of symptoms, but failed
      to eradicate the infection. The patient recovered after treatment with local and
      systemic amphotericin B, systemic 5-fluorocytosine and surgical synovectomy.
      Quantitation of joint cartilage proteoglycan fragments in synovial fluid
      indicated extensive breakdown of cartilage during the acute phase of arthritis
      but, parallel to clinical recovery, these levels returned to normal.

PMID- 8291422
TI  - Erik Moberg 1905-1993.

PMID- 8291423
TI  - Scaphotrapezio-trapezoid dislocation.

PMID- 8291424
TI  - Three-dimensional aspects of caloric nystagmus in humans: I. The influence of
      increased gravitoinertial force.
AB  - The influence of increased gravitoinertial force on the horizontal vertical and
      torsional components of caloric nystagmus response was examined. Video
      oculographic (VOG) recordings were made on a group of 10 human subjects so that
      all three components of eye movement could be evaluated. The caloric nystagmus
      response at all tested g-levels included nystagmus components around all three
      rotation axes. Over the tested range of 1.0 g to 3.0 g, the results demonstrate
      that nystagmus intensity does not increase linearly with effective
      gravitoinertial force but appears to saturate at levels of 2.0 g and beyond. It
      is proposed that the vertical and torsional nystagmus components were elicited
      both by caloric stimulation to the (anterior) vertical canals and direct thermal
      mediation to the otolithic sensory cells. Vertical LZ-nystagmus response was also
      observed during centrifuge runs (previous to caloric irrigation) at all g-levels
      and in all subjects. The caloric-induced vertical nystagmus response was also
      clearly recognisable. The observation of a reduction and inversion of nystagmus
      intensity during g-transitions agrees with earlier findings and is attributable
      to the stimulation to the canals during centrifuge acceleration, respectively
      deceleration.

PMID- 8291425
TI  - Three-dimensional aspects of caloric nystagmus in humans: II. Caloric-induced
      torsional deviation.
AB  - The oculomotor response to caloric stimulation was recorded using video
      oculography (VOG), yielding measures of eye rotation about all three orthogonal
      axes. During an ongoing caloric nystagmus response, a slow torsional deviation of
      the eye in the direction of the slow phase of the torsional component of
      nystagmus was observed. The effect appeared to be systematically influenced by
      the gravitoinertial force employed during a centrifuge study (see Part I, this
      issue), and was observed in all tested subjects. Furthermore, in subsequent
      laboratory tests warm and cold irrigations elicited opposite responses, as did
      stimulation to right and left ears. Testing in the supine and prone positions,
      however, did not lead to a reversal of direction, as is the case with the
      horizontal, vertical and torsional nystagmus components as such. The rate of
      torsional deviation was of the order of 0.05 degrees/s, well below the
      physiological transduction range of the cupular organs. Testing with a torsional
      optokinetic stimulus produced only the expected OK nystagmus without any slow
      deviation. This would argue against a central vestibular integratory, or
      oculomotor origin for the phenomenon. It is proposed that this caloric-induced,
      torsional deviation is of peripheral otolithic origin, most likely elicited by
      way of direct thermal stimulation to the hair cells of the utricular maculae.

PMID- 8291426
TI  - Oto-traumatic effects of computer simulated magnetic coil impulse noise: analysis
      of mechanisms.
AB  - The brief impulse noise artifacts of 1.0 ms or less generated by some magnetic
      coils used in extracranial magnetic stimulation may induce acoustic trauma. We
      investigated the effects of these magnetic coil acoustic artifacts (MCAA) on the
      inner ear by exposing rabbits to computer stimulated impulse noise designed to
      mimic the impulse noise of the coil in spectrum and acoustic energy. The
      simulated impulse noise stimuli (50 impulses) were varied in maximum peak sound
      pressure (160, 157, and 155 dB re: 20 muPascal), rise-time (100 microseconds and
      1,000 microseconds) and duration. The frequency spectrum of the simulated impulse
      noises were kept constant at 0.5 kHz to 7 kHz with peak energy in the 2-5 kHz
      range. The results indicated that the simulated magnetic coil impulse noise
      caused extensive cochlear damage and permanent threshold shifts largely equal to
      those induced by the MCAA. The MCAA created slightly greater PTS than the
      simulated impulse of the same peak sound pressure. Each of the 3 experimental
      stimuli induced similar PTS in the auditory range of 0.5 to 16 kHz, with the
      higher peak sound pressure stimuli (157 and 160 dB) causing greatest hearing
      loss. Increasing the rise-time of the simulated brief impulse noise from 100
      microseconds to 1,000 microseconds did not reduce the level of PTS significantly.
      The results suggest that for brief acoustic signals of around 1 ms or less, the
      peak pressure and spectral content rather than the rise-time and duration were
      the important factors in the development of noise-induced hearing loss.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8291427
TI  - Neuro-otological function in X-linked hearing loss: a multipedigree assessment
      and correlation with other clinical parameters.
AB  - Auditory and vestibular investigations were carried out in 19 affected men and 13
      obligate female carriers of 7 pedigrees with nonsyndromic hearing loss
      segregating as an X-linked trait. In addition, high resolution computerised
      tomographic scanning was carried out in 24 affected males and 12 obligate female
      carriers. The neuro-otological results confirm that non syndromic X-linked
      hearing loss is a clinically heterogeneous condition, but radiological assessment
      of the cochlea revealed two distinct groups: a normal group, and an abnormal
      group characterised by a bulbous internal auditory meatus, a dilated facial nerve
      canal and incomplete separation of the basal coil of the cochlea from the
      internal auditory meatus. Within a given pedigree there was marked consistency of
      the presence or absence of the CT scan abnormality in the affected males. One
      third of the obligate female carriers of the radiologically abnormal pedigrees
      were shown to have a similar abnormal finding, but as two thirds were normal,
      radiological examination did not predict carrier status. In the affected men,
      pure tone audiometric data did not correlate with the radiological abnormality,
      whereas vestibular function was strikingly correlated, being normal in all but
      one case in pedigrees with normal radiology and absent, or grossly impaired, in
      the pedigrees with abnormal radiology. Neuro-otological abnormalities were
      documented in approximately two thirds of the obligate female carriers, but were
      insufficiently frequent in occurrence or specific in type to be of predictive
      value.

PMID- 8291428
TI  - Fine structure of the lamina basilaris of guinea pig cochlea.
AB  - The lamina basilaris of guinea pig cochlea was studied with SEM after trypsin
      treatment, and with TEM of resin sections and deep-etching replicas. The lamina
      consists of radial, evenly compacted filaments in the zona arcuata, and radial,
      discretely bundled filaments in the zona pectinata. In both zones, elementary
      filaments measured about 12 nm in thickness on the replica. The filaments formed
      more or less irregular passing bridges with each other and, eventually, a three
      dimensional network which was continuous with the basement membrane under the
      supporting cells.

PMID- 8291429
TI  - Effects of carbogen on decreases in endocochlear potential and cochlear
      microcirculation induced by ischemia of the cochlea.
AB  - Preventive effects of carbogen on decreases in endocochlear potential (EP) and
      cochlear microcirculation induced by ischemia of the cochlea were examined in
      guinea pigs with intravital microscopy. The experimental model giving a severe
      decline in cochlear blood flow (CBF) was established by occlusion of both common
      carotid arteries and one of the vertebral arteries and i.v. infusion of adenosine
      triphosphate (ATP). The results showed no significant difference in the magnitude
      and pattern of the decrease in the cochlear microcirculation induced by ATP
      infusion and arterial occlusion before and after carbogen inhalation. However,
      even with a dramatic decrease in CBF, carbogen could reduce the decline in EP.
      The results clearly indicate that although carbogen fails to ameliorate cochlear
      ischemia in the face of a large impairment of the blood supply caused by a drop
      of blood pressure and cardiac output, it does in fact enhance the oxygen delivery
      to the cochlea and thus provide a therapeutic means of treating certain inner ear
      diseases caused by insufficient blood supply to the cochlea.

PMID- 8291430
TI  - Inner ear injury caused by air intrusion to the scala vestibuli of the cochlea.
AB  - In a previous communication, we demonstrated that the introduction of air into
      the scala tympani of the cochlea causes a decrease of cochlear potentials;
      however, the change in endocochlear dc potential (EP) was mild and the decreased
      cochlear microphonics (CM) and compound action potentials (CAP) were, at least
      partially, reversible. In contrast, we have now found that air perfusion (3-60
      microliters/min) in the scala vestibuli decreased cochlear potentials more
      drastically than that in the scala tympani. The change in the EP after air
      perfusion in the scala vestibuli was characterized by a decrease of the negative
      EP in response to anoxia. The CM drastically decreased upon the initiation of air
      perfusion and no recovery was observed after refilling of the perilymph.
      Histological examination showed collapse of Reissner's membrane in 12 out of 17
      cochleas examined. The extent and frequency of the collapse increased with an
      increase in the amount of air perfused in the scala vestibuli. As the minimal
      amount of air needed to cause inner ear damage by air perfusion in the scala
      vestibuli is as small as 3 microliters, it is possible that the prognosis is
      worse in cases with fistula of the oval window compared to that of the round
      window area, if the pneumolabyrinth is involved in the pathophysiology of
      perilymphatic fistula. It is also indicated that air inflation of the middle ear
      is dangerous in cases with fistula in the oval window.

PMID- 8291431
TI  - Ultrastructure of the endolymphatic duct in the rat. Fixation and preservation.
AB  - Ten rats were vascular-perfused at subphysiologic as well as physiologic
      pressures, 80 mmHg and 120 mmHg, respectively, employing a pressure feed-back
      controlled peristaltic pump and an isotonic perfusate/fixative with colloids (2%
      Dextran) and a hypertonic perfusate/fixative without colloids, 300 and 530 mOsm,
      respectively. In both experiments the endolymphatic duct and sac were isolated by
      microdissection after primary fixation. When comparing micrographs from the two
      experiments we observed that rats perfused at low pressure in isotonic fixative
      with colloids added had non-dilated lateral intercellular spaces and a
      subepithelial ground substance loaded with uniformly arranged microfibrils, not
      previously discovered. In rats perfused at high pressure in hypertonic fixative
      with no colloids added, we observed an edematous state in the subepithelial space
      between the solid bony aqueduct and the endolymphatic duct, with a concomitant
      derangement of previously well organized microfibrils. Furthermore, the
      epithelium was quite clearly displaced from the capillaries, the intercellular
      spaces were widely dilated and the endolymphatic duct was compressed into its
      lumen. Methods of fixation and current theories of endolymph resorption by the
      endolymphatic duct are discussed.

PMID- 8291432
TI  - Endolymphatic sac morphology after instillation of hyperosmolar hyaluronan in the
      round window niche.
AB  - One hundred and sixty-eight mice were injected with hyaluronan (HA) of varying
      tonicity in the middle ear and compared with 81 control animals to study the
      effects of hypertonic solutions in the middle ear on inner ear fluid homeostasis
      and endolymphatic sac (ES) response. Six hours after 1.9% HA and 4, 6 and 8 h
      after 4% HA deposition there was a significant increase in the proportion of
      granule-containing light epithelial cells in the ES as compared with controls
      indicating an enhanced secretory activity from the epithelial lining. Six, 8 and
      10 h after deposition of 4% HA, the ES volume was significantly reduced. The
      secretory activity and the ability of the ES to vary its volume could be specific
      responses to dehydration of the inner ear resulting from the high colloid osmotic
      pressure exerted by concentrated HA. The secretion of high-molecular substances
      into the ES may serve to keep the ES lumen patent and thus ensure a proper ES
      function and/or to regulate the intralabyrinthine volume and fluid pressure.
      Whether the findings may have clinical relevance for Meniere's patients remains
      to be elucidated.

PMID- 8291433
TI  - Electrophysiologic identification of the cochlear nerve fibers during cerebello
      pontine angle surgery.
AB  - To facilitate identification and preservation of the auditory nerve during
      cerebello-pontine angle surgery, bipolar recording of cochlear nerve compound
      action potentials (CNAPs) was performed. Two silver wires insulated with teflon
      up to the exposed ends were utilized as electrodes. They were twisted together,
      the distance between the two tips being 1 mm or less. Rarefaction polarity clicks
      (31/s) ranging from the psychoacoustical threshold to 120 dB pe SPL were used as
      stimuli. The investigation was performed in three groups of patients. The first
      group consisted of 9 patients submitted to vestibular neurectomy and 4 patients
      operated on by microvascular decompression of the eighth nerve. The second group
      comprised 8 patients with acoustic tumors smaller than 2 mm and serviceable
      hearing. Postoperative audiometric results in the subjects in the second group
      were compared with those obtained in well-matched homogeneous controls consisting
      of patients with acoustic neuroma operated on without the aid of CNAP recording.
      Bipolar recording from the eighth nerve was extremely selective, a good response
      being obtained only when positioning the electrode on the cochlear portion of the
      eighth nerve. During removal of the acoustic neuroma, repeated bipolar probing of
      the tumor and eighth nerve facilitated the task of distinguishing the cochlear
      nerve from other nervous structures and from the tumor, and contributed to
      preserving hearing in most patients.

PMID- 8291434
TI  - Fine structure of the tendon of the human stapedius muscle: comparison of normals
      and clinically otosclerotic patients.
AB  - The tendon of the human stapedius muscle was studied in normal post mortem
      material and in clinical otosclerotic patients, using light and electron
      microscopy. Cross section profiles of collagen fibrils were measured in various
      regions of the tendon and the amount of elastin was estimated. The normal
      stapedius tendon consisted of three concentrically arranged portions: A
      cylindrical central part, a tube-like mid-portion, and a cortical layer. The
      central part was made up of collagen fibrils with only a few elastic fibers, the
      mid-portion contained collagen fibrils together with significantly more elastic
      material, while the cortical layer, again, showed a smaller amount of elastic
      fibers. Mean diameters of collagen fibrils in the central part of the tendon were
      65.12 +/- 11.89 nm, in the intermediate layer 41.00 +/- 9.63 nm, and in the
      cortical layer 70.28 +/- 19.58 nm. Stapedius tendons from clinically otosclerotic
      patients, though showing the same construction, were characterized by
      significantly altered collagen fibrillar diameters (Mann-Whitney U-test). In the
      central part, mean diameters were reduced to 61.05 +/- 14.70 nm, in the mid
      portion increased to 50.90 +/- 10.08 nm, and in the cortical layer reduced to
      61.09 +/- 8.49 nm. The changes of collagen cross section profiles estimated for
      the entire tendon were significant as well: 59.68 +/- 18.74 nm in controls versus
      57.82 +/- 12.53 nm in otosclerotic patients. Elastin content in the mid-portion
      of control stapedius tendons increased with age (13% at 35 years of age to 35% at
      70 years of age).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291435
TI  - Prognostic factors for persistent middle ear effusion after acute otitis media in
      children.
AB  - The present study was carried out to determine the clinical course of acute
      otitis media (AOM) in children and to analyze the risk factors that lead to
      persistent effusion. One hundred and twenty children aged 9 months to 10 years
      diagnosed as having AOM were included in this study. Sixty-two children (52%)
      recovered from AOM without middle ear effusions within a month. In 26 cases
      (22%), middle ear effusions resolved after 1 to 3 months, while 32 children (26%)
      had persistent effusions for more than 3 months after the onset of acute
      inflammation. Statistical analysis between the group showing quick recovery and
      that with persistent effusion was carried out in relation to various clinical
      factors at the onset. The significant risk factors were: younger age, bilateral
      AOM, presence of otorrhea, tympanogram type B or C2 on an AOM ear. Moreover, the
      most significant prognostic factor was a tympanogram type B or C2 on an opposite
      ear at the acute onset. On the other hand, factors such as sex, fever, history of
      otitis media, season at onset or complications did not correlate with the
      duration of persistent effusion. From these results we conclude that careful
      examination should be performed not only on the ear with AOM but also on the
      opposite ear in order to predict the course of otitis media.

PMID- 8291436
TI  - An immuno-electron microscopic comparison of olfactory marker protein
      localization in the supranuclear regions of the rat olfactory epithelium and
      vomeronasal organ neuroepithelium.
AB  - Immuno-electron microscopy was used to examine olfactory marker protein (OMP)
      ultrastructural localization in the supranuclear regions of the rat olfactory
      epithelium (OE) and vomeronasal organ (VNO) neuroepithelium. In the OE, OMP
      immuno-reaction product was observed within the cytoplasm of olfactory
      chemoreceptor cell dendrites, vesicles and cilia. Reaction product was absent
      from olfactory microvillar cells and their unique microvillar projections. In the
      neuroepithelium of the VNO, immuno-reaction product was seen within the dendrites
      of the chemoreceptor cells, and in the bases of their attached microvilli; the
      remaining distal portions of these microvilli were unlabeled. These results
      demonstrate a difference in the distribution of OMP immunoreactivity over the
      surfaces of the rat OE and VNO. They also show that OMP immunoreactivity does not
      exist in the rat olfactory microvillar cells.

PMID- 8291437
TI  - Nasal epithelial cell culture as a tool in evaluating ciliary dysfunction.
AB  - Cultures of respiratory epithelial cells were obtained from nasal polyps
      collected in patients with and without primary ciliary defect. The ciliary
      beating frequency and the ciliary beating heterogeneity were determined on native
      and cultured tissues. We observed a significantly higher (p < 0.01) ciliary
      beating frequency of cultured ciliated cells, when compared with ciliated cells
      from the native tissue. The ciliary beating frequency of the cultured ciliated
      cells from the patient with primary defect (7.9 +/- 2.1 Hz) was significantly
      lower when compared with the beating frequency of the ciliated cells from the
      control subject (12.4 +/- 2.0 Hz). In addition, the percentage of ciliated cells
      characterized by a beating frequency lower than 8 Hz was 90.7% in the native
      tissue and 47.5% in the cultured tissue from the patient with ciliary primary
      defect. In the patient without ciliary primary defect, 90% of the cultured
      ciliated cells had a homogeneous ciliary beating, whereas in the patient with
      primary ciliary defect, only 47% of the ciliated cells had a homogeneous ciliary
      beating. These results suggest that the culture of respiratory cells associated
      with the functional activity measurement of the ciliated cells represent another
      way of precisely determining the extent of the primary ciliary dyskinesia defect.

PMID- 8291438
TI  - The effect of pressure and warmth applied to the axilla on unilateral nasal
      airway resistance and facial skin temperature.
AB  - The effect of pressure, warmth, and control stimuli applied to the axilla and
      lateral chest wall on unilateral nasal airway resistance and facial skin
      temperature was investigated in 60 healthy adults. Nasal resistance was measured
      by posterior rhinomanometry and skin temperature with an infrared thermometer. A
      significant increase in unilateral nasal resistance ipsilateral to the applied
      stimulus was seen with both pressure and warmth (p = 0.006, p = 0.02). A decrease
      in unilateral nasal resistance contralateral to the stimulus was seen in both
      these groups, but this was not significant (p = 0.45, p = 0.81). The control
      stimulus showed a non-significant increase in unilateral nasal resistance
      ipsilateral to the applied stimulus (p = 0.55), and a significant rise in
      unilateral nasal resistance on the contralateral side (p = 0.008). There were no
      significant differences between the ipsilateral and contralateral facial skin
      temperatures before or after the application of a unilateral pressure, warm or
      control stimulus. A significant bilateral increase in facial temperature was
      observed during the course of the experiment in all three groups. The mechanisms
      of induced changes in unilateral nasal resistance are discussed. The results
      increase our knowledge of the corporo-nasal reflex and demonstrate that the
      reciprocal changes in sympathetic tone to the nasal capacitance blood vessels are
      independent from any parallel reflex changes in sympathetic tone to cutaneous
      blood vessels.

PMID- 8291439
TI  - Nasal reaction to changes in whole body temperature.
AB  - The changes in nasal patency following a 1.5 degrees C decrease or increase in
      whole body temperature were measured in 8 healthy young males, during and after
      30 min of immersion in a 15 degrees C cold or a 40 degrees C warm bath, breathing
      air at the same temperature, in a cross-over experimental design. The nasal
      reactions were traced by consecutive measurements of changes in nasal cavity
      volumes by acoustic rhinometry. Swelling of the mucosa during cooling and an
      almost maximal shrinkage of the mucosa during heating were indicated by
      respectively a decrease and an increase in nasal cavity volumes. The reactions
      were determined predominantly by the whole body thermal balance, but were also
      influenced by the temperature of the inhaled air, either enhanced, reduced or
      temporarily reversed. The greatest change occurred in the nasal cavity, left or
      right, which differed most from the final state at the beginning of exposure due
      to the actual state of nasal cycle.

PMID- 8291440
TI  - Heterologous epidermal growth factor receptor (EGF-R) expression in larynx cancer
      cell lines: evidence for the existence of structurally modified receptors.
AB  - Overexpression of epidermal growth factor receptor (EGF-R) is a common
      characteristic of epidermoid tumors and its expression in head and neck squamous
      cell carcinoma biopsies and cell lines has been reported previously by several
      authors. With the aim to provide more structural and functional details about the
      protein overexpression of EGF-R in head and neck squamous cell carcinomas, the
      expression of this molecule was studied in four larynx carcinoma cell lines (HLaC
      78, HLaC-79, UM-SCC-17A and UM-SCC-17B). The results were compared with those
      from a spontaneously immortalized aneuploid human keratinocyte cell line (HaCaT)
      and cultured fresh skin keratinocytes. The EGF-R identification was performed
      using two well characterized monoclonal antibodies (MoAb) which recognize antigen
      determinants located on the extracellular domain of the receptor: EGF-R I and
      29.1.1. Cytocentrifuge smears and cell suspensions were prepared for flow
      cytometric analysis. With the monoclonal antibody EGF-R I the highest EGF-R
      expression was obtained in the cell line UM-SCC-17A, whereas the cell line with
      the highest EGF-R overexpression was the HLa-C-78 if the monoclonal antibody
      29.1.1 was used. The cultured keratinocytes always showed a histogram similar to
      the control sample (cells were incubated with the second antibody alone). These
      results could be explained by the existence of structurally modified EGF
      receptors. Further studies including possible differences in both the
      autophosphorylization and the kinase activities are in progress to clarify the
      functional repercussions of these observed structural defects.

PMID- 8291441
TI  - Establishment and immunohistochemical characterization of an experimentally
      induced transplantable malignant schwannoma in the rat and two derived cell
      lines.
AB  - Oral administration of N-methyl-N'-nitro-N-nitrosoguanidine induced
      gastrointestinal tumors in 15 out of 19 rats: six adenomas, seven
      adenocarcinomas, one fibrosarcoma and one malignant schwannoma that was
      homotransplantable. Both the original and transplantable tumor exhibited
      characteristic morphological features and immunoreactivity identical to that of a
      human malignant schwannoma: positive reaction for S-100 protein, neuron specific
      enolase, glial fibrillary acidic protein, myelin basic protein and vimentin. In
      addition, alpha-smooth muscle actin was expressed in both tumors. Cultured tumor
      cells derived from the transplantable tumor at passage 3 produced 18 clones which
      showed anchorage independent growth in soft agar. From these clones, two cell
      lines showing characteristic immunoreactivity, designated as RMS-1 and 2, were
      established. In general, the immunoreactivities of the two cell lines were
      similar to those of the original tumor; however, the RMS-1 cell line demonstrated
      positive immunoreaction for neurofilaments and RMS-2 was negative for alpha
      smooth muscle actin. Subcutaneous, injection of cultured cells from both cell
      lines into athymic BALB/c nude mice induced tumors identical to the original
      tumor. In the present study, transplantable malignant schwannoma was established
      in the rat and two phenotypes were isolated and established as cell lines.

PMID- 8291442
TI  - Immunohistochemistry of neuronal inclusions in the cerebral cortex and brain-stem
      in Lewy body disease.
AB  - Three cases of Lewy body disease were investigated in order to compare the
      morphological and immunohistochemical characteristics of the neuronal inclusions
      in the cerebral cortex (CC) and brain-stem (BS). Ultrastructurally, the CC
      contained intermediate-sized filaments with variable amounts of granular material
      and other organelles, whereas the BS consisted of an electron-dense core and an
      outer area with radially oriented filaments. The cerebral cortex was immuno
      reactive with antibodies against tyrosine hydroxylase (TH) and tau protein, and
      differed from BS. In addition, although the CC were antigenically similar to BS
      in their neurofilament (70, 160 and 200 kDa) and ubiquitin contents, the
      localization of neurofilament immunoreactivity differed between them, being
      confined positively to the core of CC, but to the periphery of the BS. Although
      Lewy bodies (LB) in idiopathic Parkinson's disease are morphologically similar to
      BS, they have been reported to differ in their immunoreactivity with antibodies
      against tau. It has been reported that CC differ from LB with regard to
      immunoreactivity with antibodies against TH and tropomyosin. It is inferred that
      these inclusions (CC, BS and LB) differ in morphogenesis.

PMID- 8291443
TI  - Morphologic variations of dense deposit disease: light and electron microscopic,
      immunohistochemical and clinical findings in 10 patients.
AB  - Twenty-one renal biopsy specimens obtained from 10 patients with dense deposit
      disease (DDD) were investigated using light microscopy, electron microscopy and
      immunohistochemistry. The patients included four females and six males aged 6 to
      35 years (mean 16.1 years). A morphological diagnosis of DDD was made following
      the ultrastructural detection of continuous intramembranous dense deposits
      (CIMDD) in some capillary loops of at least one of the series of the repeated
      biopsies from each patient. With light microscopy, six patients showed
      membranoproliferative glomerulonephritis (MPGN). The other four patients showed
      diffuse proliferative glomerulonephritis (DPGN) with acute lesions showing
      intraglomerular neutrophilic infiltration, hump formation and endothelial
      swelling in three and minor glomerular abnormalities in one. Follow-up biopsies
      were obtained in six patients. Two patients progressed from DPGN to MPGN within 7
      months, whereas three patients with MPGN showed morphologic improvement that
      featured increased capillary patency and regional disappearance of dense deposits
      along with the reduction of proteinuria. Dense deposit disease did not always
      feature typical amorphous and osmiophilic CIMDD spreading across the whole width
      of the lamina densa. This classical ultrastructural manifestation was mainly
      found in the patients with histologic non-MPGN and a linear peripheral pattern of
      complement component (C3) deposition. The MPGN patients with a granular
      peripheral pattern of C3 deposition also had CIMDD, but also additionally
      featured less dense subepithelial deposits superimposed on the CIMDD to produce
      an appearance simulating membranous transformation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8291444
TI  - Establishment and characterization of a human lung adenocarcinoma cell line (LC
      2/ad) producing alpha 1-antitrypsin in vitro.
AB  - A new human cell line, LC-2/ad was established from pleural effusion of pulmonary
      adenocarcinoma of a 51 year old Japanese female. The LC-2/ad cells exhibit an
      epithelial appearance and a tendency to form small domes as observed with phase
      contrast microscopy. The modal chromosome number was 53-56. Plating efficiency
      and doubling time were 6.8% and 58 h, respectively (32th passage).
      Immunocytochemically, the cells were strongly positive for CEA and cytokeratins
      including cytokeratin no. 18 which is present in simple epithelia.
      Ultrastructurally, the cultured cells were characterized by well-formed
      junctional complexes and microvilli. Subcutaneous injection of 5 x 10(6) cells
      into a nude mouse resulted in tumor formation classified histologically as a
      moderately differentiated adenocarcinoma. This cell line produced at least two
      functionally active trypsin inhibitors together with several proteinases in
      vitro. The main inhibitor was purified partially from the serum-free conditioned
      medium and confirmed immunologically as human alpha 1-antitrypsin (AAT).
      Immunohistochemically, the xenografted tumor was also positive for AAT. The cell
      line LC-2/ad is useful for the study of tumor-derived serine proteinase
      inhibitors, in particular AAT.

PMID- 8291445
TI  - Epstein-Barr virus related gastric cancer in Japan: a molecular patho
      epidemiological study.
AB  - Epstein-Barr virus (EBV) involvement in gastric carcinoma has been demonstrated
      by the presence of EBV genomes and EBV-encoded small RNA (EBER) in the carcinoma
      cells, monoclonal proliferation of EBV-infected carcinoma cells and elevated
      antibody titers. The present study was conducted to investigate the prevalence of
      EBV involvement among gastric carcinomas observed in nine Japanese cities with
      varying gastric cancer rates. In situ hybridization of EBER-1 was applied to
      paraffin sections from 1848 carcinomas observed in 1795 cases and EBV involvement
      was detected based on uniform hybridization in carcinoma cells. Epstein-Barr
      virus was detected in 6.6% of lesions and 6.7% of cases. The rate of EBV
      involvement did not vary significantly for each city and there was no correlation
      with underlying gastric cancer mortality rates. Thus, geographic variation of
      gastric cancer rates within Japan cannot be explained in terms of EBV
      involvement. Epstein-Barr virus-related gastric carcinoma is one of the most
      common EBV-related tumors in Japan. The involvement of EBV was significantly more
      frequent among males than among females, mainly for cancers occurring in the
      upper and middle part of the stomach, and exhibited more variation by cell type
      among males. These observations suggest that other factors yet to be discovered
      may modulate the causal role of EBV in gastric carcinogenesis.

PMID- 8291446
TI  - Identification of basic fibroblast growth factor in papillary carcinoma of the
      thyroid.
AB  - Basic fibroblast growth factor (bFGF) was identified in the papillary carcinoma
      of the human thyroid. Immunohistochemically, it was found that the reactivity for
      bFGF was localized in the cytoplasm of the neoplastic cells of the five papillary
      carcinomas. However the extract of the papillary carcinomas contained the
      mitogenic activity for endothelial cells. This bioactive molecule was determined
      as bFGF by using the heparin-Sepharose affinity chromatography and western blot
      analysis. The bFGF derived from human thyroid papillary carcinoma and the
      recombinant human bFGF stimulated the bromodeoxyuridine incorporation by the
      cultured human thyroid papillary carcinoma cells. These cells also showed
      positive staining for thyroglobulin and cytokeratin. These results indicate that
      bFGF, probably produced by the neoplastic cells, plays an important role in the
      development of papillary carcinoma of the thyroid with stimulation of
      angiogenesis as well as proliferation of the parenchymal cells.

PMID- 8291447
TI  - Relationships between nodal status and cell kinetics, DNA ploidy pattern and
      histopathology of the deeply infiltrating sites in colorectal adenocarcinoma.
AB  - Tumor cell kinetics and DNA contents were investigated by in vitro labeling with
      bromodeoxyuridine (BrdU) and flow cytometry using paraffin-embedded specimens in
      both superficially (Sup) and deeply (Deep) infiltrating sites of 28 colorectal
      adenocarcinomas. Eleven were well differentiated and 17 were moderately
      differentiated adenocarcinomas. In moderately differentiated adenocarcinoma,
      histologic low grade types of Deep were frequently associated with lymph node
      metastasis, but the BrdU labeling indices (LI) or tumor DNA ploidy pattern did
      not correlate with nodal status. Among the seven aneuploid tumors of moderately
      differentiated adenocarcinoma, the BrdU LI and histology of Deep tended to
      correlate with nodal status. These findings suggest that the histology of Deep
      should have a greater significance than tumor cell kinetics or DNA contents. They
      also suggest that the tumor DNA ploidy pattern may be heterogeneous and divided
      into subgroups according to its cell kinetics or histology of Deep in relation to
      lymph node metastasis.

PMID- 8291448
TI  - Ileal duplication cyst associated with heterotopic pancreas: report of a case and
      literature review.
AB  - A rare case of solitary ileal duplication cyst accompanied by heterotopic
      pancreas in the terminal ileum is presented. An 8 year old boy with an ovoid
      shaped, elastic soft and pendant-growing ileal duplication cyst associated with
      aberrant pancreatic tissue but not communicating with the lumen of the ileum,
      underwent an adhesiotomy for a small intestinal adhesion that caused bowel
      obstruction. The obstructive state of the intestine seemed to be caused by an
      inflammation of the duplication cyst which was 4.5 x 2.7 x 2.5 cm and oval in
      shape. Excision of the cyst and the heterotopic pancreas was curative. The
      histological findings were identical to heterotopic pancreas accompanied by ileal
      duplication without any clinical features of heterotopic pancreas. A review of
      the literature is presented along with the author's experience in a case of ileal
      duplication cyst associated with heterotopic pancreas located in the ileum.

PMID- 8291449
TI  - Recurred Castleman's disease containing a fibrohistiocytic nodular lesion with
      vascular occlusion.
AB  - A recurring case of Castleman's disease containing a fibrohistiocytic nodular
      lesion is presented. The recurred tumor was found in the mediastinum of a 40 year
      old Japanese female who had undergone the extirpation of a mediastinal tumor 18
      years previously and had been suffering from rheumatoid arthritis 5 years after
      the initial removal. Microscopically, the present tumor and the initial removed
      tumor fulfilled the morphologic criteria for the hyaline-vascular type of
      Castleman's disease. A well-demarcated nodular lesion (1.5 cm in diameter) was
      located in the present tumor. It consisted of interlacing oval to short spindle
      shaped cells positive for factor XIIIa and vimentin, merging with lymphocytes,
      plasma cells, macrophages and capillaries lined by swollen endothelial cells.
      Mitotic figures were not noted. Foci of hemorrhage and necrosis were also not
      detected. The stenosis or occlusion of the large vessels due to intimal fibrosis
      and medial hypertrophy was observed around the nodular lesion.

PMID- 8291450
TI  - Lung carcinoma mimicking malignant lymphoma: report of three cases.
AB  - Three cases of lung carcinomas with unusual histologic appearances that have
      received little or no comment in the literature are presented. They were
      initially confused with malignant lymphoma because of a diffuse proliferation of
      relatively monotonous cells simulating large-cell immunoblastic lymphoma. In each
      case, the possibility of malignant lymphoma was excluded with confidence after
      the immunohistochemical study (leucocyte common antigen negative and cytokeratins
      positive), although with conventional microscopy several foci of cohesive groups
      of tumor cells were observed. The tumors were ranked at the clinical stage II or
      III when they were initially discovered, but all patients died of disease within
      1 year. The present three tumors show an aggressive behavior and could be
      classified into a peculiar variant of 'large cell' carcinoma. It is necessary for
      surgical pathologists to have an idea of these variants of lung carcinoma in
      order to avoid erroneous diagnosis.

PMID- 8291451
TI  - Small round and spindle cell sarcoma with neuronal differentiation and oncocyte
      like features of the thoracic wall: a case report with histological,
      immunohistochemical and ultrastructural examinations.
AB  - A case of small round and spindle cell sarcoma with neuronal differentiation and
      oncocyte-like features is presented. The tumor was encountered in a 32 year old
      Japanese woman with an initial presentation of palpable tumor in the left lateral
      region of the thorax. The resected tumor was a partially well encapsulated
      whitish medullary one and consisted of small round and spindle tumor cells,
      together with so-called rhabdoid cells in the small round cell area. Although
      pseudorosettes were often observed, true rosette formation could not be detected
      anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most
      tumor cells possessed numerous mitochondria, some of which occasionally contained
      abnormal filamentous or crystalloid structures. Various amounts of microfilaments
      were present in most tumor cells and microtubules were present in a few. A
      minority of small round cells possessed a small number of neurosecretory
      granules, especially in short cytoplasmic processes. A positive immunoreaction
      for neuron specific enolase was found by immunohistochemical examination in
      several small round tumor cells and for neurofilaments in lesser numbers. Despite
      the lack of S-100 protein, MB2 was detected in both small round and spindle
      cells. On the basis of these findings, the tumor of the present case corresponds
      to malignant peripheral nerve sheath tumor with neuronal differentiation and
      oncocytic features.

PMID- 8291452
TI  - Effects of ovarian surgery on the dopaminergic and opioidergic control of
      gonadotropin and prolactin secretion in women with polycystic ovarian disease.
AB  - Ovarian surgery has been demonstrated as an effective means to establish regular
      menstrual cycles and resumption of ovulation in patients with polycystic ovarian
      disease (PCO). We questioned whether such reinstitution of menstrual cyclicity
      may be associated with changes in the opioidergic and dopaminergic activity known
      to be aberrant in these women. Opioidergic and dopaminergic tone was therefore
      assessed in patients with PCO before and after ovarian laser vaporization (n = 4)
      or classical ovarian wedge resection (n = 4). Blood samples for the determination
      of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin
      were frequently obtained following opioidergic and/or dopaminergic antagonism
      affected by naloxone (4 mg i.v.) or metoclopramide (10 mg i.v.). In response to
      either surgical approach, circulating LH levels decreased (p < 0.01), while FSH
      concentrations remained unaltered. Further, LH and FSH concentrations did not
      noticeably change following challenges with naloxone or metoclopramide: this
      applied to conditions before and after ovarian surgery. Prolactin release in
      response to metoclopramide was markedly (p < 0.01) higher following ovarian
      surgery than before. Thus, both ovarian laser surgery and classical wedge
      resection can effectively restore normal menstrual cyclicity in PCO patients,
      although they failed to alter opioidergic and dopaminergic activity. Dopaminergic
      inhibition of prolactin secretion was further enhanced after ovarian surgery.
      These observations suggest that different modes of ovarian surgery are effective
      in influencing central gonadal control, but that the central opioidergic and
      dopaminergic control of gonadotropin and prolactin secretion remains unaffected
      by ovarian surgery in PCO women, even when menstrual cyclicity is resumed.

PMID- 8291453
TI  - Measurement of serum levels of exogenously administered FSH and LH during
      ovulation induction therapy.
AB  - We conducted a prospective study of blood levels of follicle stimulating hormone
      (FSH) and luteinizing hormone (LH) following daily intramuscular injection of
      human menopausal gonadotropin (hMG) containing equal proportions of FSH and LH.
      Blood samples were collected on alternate days and the resulting changes in the
      blood levels of the ovarian hormone estradiol were also monitored. Twenty-eight
      consecutive patients with polycystic ovary syndrome who were between the ages of
      25 and 35 years and attending our infertility clinic for ovulation induction
      therapy and assisted pregnancy were studied. Polycystic ovary syndrome was
      diagnosed on laparoscopy and as evidenced by high serum LH which was three times
      greater than FSH in the follicular phase of the menstrual cycle. A male factor
      for infertility was excluded. Twenty-five out of 28 women (89.3%) receiving hMG
      responded to therapy by a rise in serum estradiol level (> 1200 pmol/l on day 9).
      Of the 25 women who responded to hMG, four had live single babies (16%). All four
      women showed a cumulative rise in mean serum FSH with treatment when measured by
      standard radioimmunoassay, reaching statistical significance on day 5 (p < 0.05).
      The remaining 21 who failed to become pregnant showed variable changes in mean
      serum FSH with a sharp rise on day 3 (p < 0.02) and a significant fall on day 7
      (p < 0.02). However, mean serum LH measured by standard radioimmunoassay in all
      women remained unchanged throughout the period of treatment.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8291454
TI  - Heterogeneity of human prolactin levels in serum during the early postpartum
      period.
AB  - The distribution of molecular forms of prolactin in serum of women during the 1st
      postpartum week was studied using column chromatography. Serum was analyzed 1, 4
      and 7 days postpartum. Using this technique, three molecular forms of prolactin
      were detected with approximate molecular weights of < or = 100, 48 and 22 kDa;
      these were termed 'big-big', 'big' and 'little' prolactin, respectively. The
      relative amount of each form was measured in relation to the total amount of
      immunoreactive prolactin eluted from the column. Throughout the first postpartum
      week big-big prolactin represented a minor fraction of the total immunoreactive
      prolactin in the serum of lactating women: 4.9%, 5.2% and 4.6% on days 1, 4 and
      7, respectively. There was a gradual decrease in the higher molecular weight
      forms of prolactin (big-big plus big prolactin) from the 1st to the 7th
      postpartum day. This was associated with a significant increase of the little
      prolactin from 62.8 +/- 7.2% at the 1st postpartum day to 72.6 +/- 6.5% at the
      7th day (p < 0.05).

PMID- 8291455
TI  - 24-hour serum cortisol profiles in women with polycystic ovary syndrome.
AB  - We studied the 24-h blood profiles of cortisol in obese and non-obese women with
      polycystic ovary syndrome (PCOS), for comparison with the levels in healthy women
      (controls). The levels of other hormones, such as androgens, which are known to
      be disturbed in PCOS, were also compared. Luteinizing hormone (LH) and androgen
      (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS))
      concentrations were significantly (p < 0.005) raised in patients with PCOS,
      compared to those in control women. Sex hormone binding globulin (SHBG)
      concentration was significantly lower in women with PCOS, particularly in those
      who were overweight. There was a significant negative correlation between body
      mass index (BMI) and SHBG concentrations (r = -0.59; p = 0.006). Mean 24-h
      cortisol concentrations were similar in women with PCOS and controls, as well as
      in the obese and non-obese PCOS patients. However, the 24-h blood cortisol
      profile pattern was significantly different in women with PCOS as compared to the
      controls (p = 0.0039). Significantly lower cortisol levels were observed during
      the night (levels were determined between 20.00 and 04.00 and are expressed as
      the area under the curve) in subjects with PCOS, compared to the control women (p
      = 0.02). These changes were most marked in the non-obese women with PCOS who had
      lower blood cortisol levels during the night than either the controls or the
      obese PCOS subjects. Our finding of significantly lower cortisol concentrations
      during the night could reflect a subtle abnormality of adrenal steroid secretion
      in women with PCOS.

PMID- 8291456
TI  - Effects of tamoxifen on endometrial estrogen and progesterone receptor
      concentrations in women with fibrocystic disease of the breast.
AB  - Endocrine changes were determined after a 3-week cycle of tamoxifen treatment in
      11 regularly cycling women with clinical and radiological evidence of fibrocystic
      disease of the breast. Blood and endometrial samples were obtained during the
      luteal phase prior to and at the end of treatment. Tamoxifen treatment (20 mg/day
      orally for 3 weeks), produced a significant increase in plasma estradiol (p =
      0.0018) without simultaneous changes in plasma luteinizing hormone, follicle
      stimulating hormone, prolactin or progesterone. Tamoxifen treatment significantly
      reduced endometrial estrogen receptor levels compared to the control cycle (p =
      0.0018) while endometrial progesterone receptor levels remained unchanged.
      Endometrial histological studies showed secretory transformation in both the
      control cycle and after tamoxifen treatment. The reduction in endometrial
      estrogen receptor concentrations would suggest a tamoxifen-induced effect or a
      down-regulatory mechanism to protect target tissues from high estradiol levels.
      These changes were not associated with alterations in either plasma progesterone
      or endometrial progesterone receptor concentrations. The tamoxifen-induced
      changes did not produce any interference in the glandular secretory response of
      the endometrium.

PMID- 8291457
TI  - The effects of levonorgestrel, desogestrel and gestodene on the pulsatile release
      of luteinizing hormone in oral contraceptive users.
AB  - The dynamics of luteinizing hormone (LH) and follicle stimulating hormone (FSH)
      release were investigated in 60 long-term oral contraceptive (OC) users. Five
      different types of OC, all containing the same amount of estrogens were studied:
      three monophasic preparations containing levonorgestrel, desogestrel and
      gestodene, respectively, and two triphasic formulations, containing
      levonorgestrel or gestodene. Thirteen healthy, normally cycling volunteers served
      as controls. Blood sampling was performed at 10-min intervals during a 6-h period
      to determine the pulsatile release of LH. LH and FSH were measured using a
      sensitive immunoradiometric assay. Pulse patterns were classified on the basis of
      the overall LH level, as well as on the character of the LH pulses, according to
      both frequency and amplitude characteristics. Pulsatile LH release was maintained
      during OC use. After the 7-day pill-free interval, FSH levels as well as the LH
      pulse patterns were comparable to those of early follicular-phase controls. FSH
      levels and FSH release in response to a gonadotropin releasing hormone (GnRH)
      challenge were profoundly suppressed in all OC users, as early as day 8 of the
      pill cycle. LH release during the pill cycle was characterized by either a low
      frequency (median 1 pulse/6 h), high amplitude (median 2.5 IU/l) pulse pattern or
      by a pattern of low-amplitude pulses (median 0.2 IU/l) and low basal LH levels
      (median 0.2 IU/l). The distribution of these pulse patterns showed marked
      differences between different OC preparations and depended on both the type and
      dose regimen of the gestagenic component of the OC.

PMID- 8291458
TI  - A new fluoride preparation for the prevention of postmenopausal osteoporosis:
      calcium monofluorophosphate.
AB  - Fifty-six postmenopausal women aged 52.4 +/- 6.7 years (SD) were treated for 12
      months with L-glutamine calcium monofluorophosphate. Each patient received four
      tablets/day, providing a total dose of 20 mg of fluoride and 600 mg of elemental
      calcium. Bone mineral density was measured at baseline and after 6 and 12 months
      of treatment by dual photon absorptiometry of the distal forearm. At these times,
      serum levels of alkaline phosphatase and osteocalcin, and urinary concentrations
      of hydroxyproline and calcium, were also assayed. Results were compared with a
      control group of 50 untreated postmenopausal women with similar clinical
      characteristics. Forty-nine patients completed the study. Bone mineral density in
      the treated patients showed a significant increase after 6 months in comparison
      with both baseline (p < 0.01) and controls (p < 0.01). After 12 months no
      significant further increase in bone mineral density was detected. In the control
      group, a significant decrease of bone mineral density was observed at this time
      (p < 0.01). After 6 months, serum osteocalcin levels were significantly increased
      in the treated group (p < 0.01 vs. basal and controls). The other biochemical
      parameters did not show any significant variations. After 12 months, all the
      biochemical parameters evaluated, with the exception of serum alkaline
      phosphatase, were significantly different in comparison with the control group (p
      < 0.01). Osteocalcin levels also increased in comparison with the basal value (p
      < 0.01). Adverse effects were mild. However, seven patients stopped the treatment
      before the 6th month because of gastrointestinal complaints.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8291459
TI  - Different types of extragenital endometriosis: a review.
AB  - Endometriotic growth may appear in any structure in the body. As well as
      affecting the internal genitalia, lesions are not uncommon in the bowel, urinary
      tract and thorax and reports of a number of cases at rarer sites have been
      published. This review is based on more than 1000 publications on the subject,
      that allows an overview of the appearance of the disease in different organs.

PMID- 8291460
TI  - Cerebral ischemia.

PMID- 8291461
TI  - Cerebral hemorrhage.

PMID- 8291462
TI  - Maternal head trauma during pregnancy.

PMID- 8291463
TI  - Central nervous system neoplasms in pregnancy.

PMID- 8291464
TI  - Infections during pregnancy.

PMID- 8291465
TI  - Movement disorders and pregnancy.

PMID- 8291466
TI  - Peripheral nerve disorders in pregnancy.

PMID- 8291467
TI  - Muscle disease in the pregnant woman.

PMID- 8291468
TI  - Pregnancy in women with paraplegia.

PMID- 8291469
TI  - Psychiatric disorders and pregnancy.

PMID- 8291470
TI  - Cocaine and alcohol use in pregnancy.

PMID- 8291471
TI  - Neurodiagnostic imaging of the pregnant patient.

PMID- 8291472
TI  - Legal issues: roles of physicians in preventing fetal harm.

PMID- 8291473
TI  - Eclampsia.

PMID- 8291474
TI  - Endocrine aspects of epilepsy in women.

PMID- 8291475
TI  - Epilepsy and pregnancy.

PMID- 8291476
TI  - Low-back pain in pregnancy.

PMID- 8291477
TI  - Migraine and pregnancy.

PMID- 8291478
TI  - Multiple sclerosis and pregnancy.
AB  - Gestation is a period of decreased risk for a relapse of MS, whereas the 3 months
      postpartum is a period of high risk. Taken together, the pregnancy year may also
      be a period of higher risk for relapse than non-pregnancy periods. However, the
      lifetime risk rate does not appear to change because of pregnancy, and on the
      basis of current retrospective studies, long-term disability is not higher in
      pregnant women or even women experiencing relapses during the pregnancy year. MS
      has little or no effect on the course of pregnancy or delivery, although patients
      with severe MS may have difficulty fully caring for their newborns. The decision
      to become pregnant should be made by the patient and her husband after they are
      appropriately informed about the risks involved.

PMID- 8291479
TI  - Neurologic aspects of rheumatologic disorders during pregnancy.

PMID- 8291480
TI  - [Molecular cell glycobiology of the retina].
AB  - The distribution of beta-galactoside alpha 2,6-sialyltransferase (alpha 2,6-ST)
      mRNA in the retina was examined using in situ hybridization histochemistry to
      study the relation of sialic acid to retinal glycoconjugates. In rod-dominant rat
      retinas, the alpha 2,6-ST, which was found to be newly expressed in the
      photoreceptor inner segments on post-natal day (P) 16, appears to sialylate the
      rod-associated interphotoreceptor matrix (IPM). In cone-dominant squirrel
      retinas, alpha 2,6-ST mRNA was sparse, which suggests that cone-associated IPM
      does not contain sialic acids. The light-response of the IPM first occurred
      between P14 and P16. The IPM around cone photoreceptors did not show the
      response. These observations suggest that the presence of sialic acids on the
      termini of sugar chains around rods plays an important role in generating the
      light response of the IPM. The electrical resistance of the IPM is increased by
      removing sialic acids from the glycoconjugates of the IPM. The electrical
      resistance of the rod-associated sialo-IPM may be lower than that of the cone
      associated asialo-IPM. The light response of the rod-associated IPM may not only
      facilitate the transfer of substances between rod photoreceptors and the retinal
      pigment epithelium, but may also be involved in the generation of the
      physiological features of rods. A different distribution of alpha 2,6-ST mRNA was
      detected in light-adapted and dark-adapted rat retinas. The mRNA was diffusely
      distributed through-out the inner segments in light-adapted retinas, but it was
      scarce in basal inner segments in dark-adapted ones. The second phase of the IPM
      light response, histologically detected as accumulation of the IPM around inner
      segments, may be induced by an increase in the synthesis of N-glycoside linked
      glycoconjugates containing sialic acids. Comparing this and the electron
      microscopic examination of free ribosomes in the inner segments, the dispersed
      and clustered ribosomes correspond to active and inactive types, respectively. A
      progressive decrease in the mRNA-expression of alpha 2,6-ST was commonly observed
      in the process of various types of retinal degeneration.

PMID- 8291482
TI  - [Eye bank eye and research].

PMID- 8291481
TI  - [Molecular biological approaches to eye development].
AB  - Many genes are expressed coordinately and proteins coded by these genes interact
      with one another in development of the eye. Candidates for such factors are
      growth factors, hormones, and their receptors, transcriptional factors such as
      homeodomain-containing proteins. The following experiments were done in order to
      understand their roles in eye development. I. Analysis of Pax-6 gene in a rat
      strain with small eye phenotype. A mutant rat strain "rSey (rat small eye)"
      showed absence of both the nasal placode and the lens placode in homozygotes,
      which resulted in nasal malformation and lack of the eyes. This phenotype was
      similar to that of a mouse mutant "Sey (small eye)" with mutations of the Pax-6
      gene, which motivated me to analyze the Pax-6 gene in the mutant rat. An exon of
      the Pax-6 genomic DNA in the homozygote had a novel dinucleotide (GT) due to one
      base (G) insertion, which served as an abnormal 5' donor splice site and
      generated an internal deletion of the messenger RNA. The homozygote also showed
      impaired migration of neural crest cells originating from the anterior midbrain,
      indicating that the Pax-6 gene would be conducting migration of the neural crest
      cells. II. Localization of transcripts by in situ hybridization. 1. Retinoic acid
      receptor. Retinoic acids are teratogenic and exposure to them causes facial
      malformation including eye anomalies. Three types (alpha, beta, gamma) are known
      as receptors for all-trans retinoic acids. Transcripts for all the types were
      found in neural crest and its derivatives around and inside of the optic cup in
      mouse embryos. The finding is consistent with the fact that neural crest cells
      are involved in malformation caused by retinoic acids. 2. Fibroblast growth
      factor. Fibroblast growth factors exert effects on differentiation,
      proliferation, and survival of various kinds of cells in the eye. Three types
      (types 1, 2, and 3) of fibroblast growth factor receptors have been discovered in
      chick. The type 1 receptor was expressed mainly in the neuroepithelial layers of
      the optic cup, and the type 2 receptor was expressed in mesenchymal cells of
      neural crest origin around the optic cup of chick embryos. In contrast,
      transcripts for the type 3 receptor were detected at a high level in the lens
      vesicle. Different types of the receptor expressed in structures of different
      origins indicate that fibroblast growth factors would be involved in signaling
      among these different structures in eye development. 3. Activin
      receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8291483
TI  - A case report of a complete unilateral cleft of the lip and the palate from birth
      to 15 years.

PMID- 8291484
TI  - Surface characterization of ceramic brackets: a multitechnique approach.
AB  - The purpose of this study was to investigate the microstructure and bonding
      mechanisms for four types of ceramic brackets by using information from several
      methods. Two of the bracket types provided exclusively micromechanical retention
      as a bonding mechanism, with the use of microspheres or microcrystals to achieve
      a rough structure for the bracket base. A silane layer that provided chemical
      adhesion was found to cover the bases of the two other types of brackets; one
      type also used central regions of increased roughness to provide additional
      micromechanical retention. Polarized-light optical microscopy showed that the
      silane layer was not continuous. Small area x-ray photoelectron spectroscopy
      analysis (SAXPS) of the silane layer was consistent with the presence of gamma
      methacryloxypropyl trimethoxysilane. The study of the ceramic bracket bases
      revealed a wide variety in composition, structure, morphologic condition, and
      coating treatment that implies different bonding mechanisms to orthodontic
      adhesives.

PMID- 8291485
TI  - Qualified personal residence trust: discounted gift of residence to children.

PMID- 8291486
TI  - Problems of transfers and records--a legitimate concern.

PMID- 8291487
TI  - Problems of transfers and records--a legitimate concern.

PMID- 8291488
TI  - Problems of transfers and records--a legitimate concern.

PMID- 8291489
TI  - Vertical changes following first premolar extractions.
AB  - Orthodontic treatment involving the extraction of first premolars has been
      implicated in the dental literature as an etiologic factor in the development of
      temporomandibular joint (TMJ) disorders. Authors have proposed that the
      extraction of first premolars causes a decrease in the vertical dimension of
      occlusion. The purpose of this study was to investigate the validity of this
      claim. Records of 45 Class I, nonextraction cases and 38 Class I, first premolar
      extraction cases were obtained. The pretreatment and posttreatment cephalographs
      were digitized, and several cephalometric variables were examined to evaluate the
      vertical changes occurring as a result of orthodontic treatment. Statistical
      analysis of the data revealed no significant differences between the vertical
      changes occurring in the extraction and nonextraction groups. On average,
      orthodontic treatment in both groups produced an increase in the cephalometric
      vertical dimensions that were examined.

PMID- 8291490
TI  - Effects of patient age on postorthodontic stability in Class II, division 1
      malocclusions.
AB  - The increase in the proportion of adults in the typical orthodontic practice
      merits closer scrutiny of the treatment differences involved in adult vis-a-vis
      adolescent patients. Orthodontic treatment in the adolescent relies heavily on
      growth; in the adult, the practitioner must reposition teeth within the
      nongrowing arches. This difference may create the potential for greater
      postretention relapse in the adult; alternatively, continued growth in the
      subadult might detract from stability of the case. Two samples of Class II,
      Division 1 cases, all treated by one specialist, were examined an average of 5
      years out of treatment. One group had been treated during adolescence
      (approximately 12 years of age), the other in adulthood (approximately 28 years).
      The orthodontic corrections were stable in both groups, but for different
      reasons: Posttreatment changes in the bony and dental structures of the adults
      were minimal. Bony changes (i.e., continued midface and mandibular growth) were
      appreciable in adolescents, and this growth--notably growth of the mandible-
      compensated for unfavorable drift of the dental elements (primarily mesial shift
      of the maxillary molar) after treatment. In sum, orthodontic corrections in
      adults were found to be at least as stable as those in the conventional
      adolescent patient.

PMID- 8291491
TI  - Eighteen-month evaluation of the effects of a 0.4% stannous fluoride gel on
      gingivitis in orthodontic patients.
AB  - The purpose of this study was to determine whether conventional toothbrushing and
      twice daily use of a brush-on 0.4% stannous fluoride (SnF2) gel containing more
      than 90% available Sn2+ would be more effective for controlling plaque
      accumulation and gingivitis in the presence of orthodontic appliances than
      conventional toothbrushing alone. Consecutively treated adolescents who were to
      receive full-mouth fixed orthodontic appliances were assigned to one of two
      groups according to age and sex criteria. The first group (control, n = 35) used
      toothbrushing with a standard fluoride toothpaste, whereas the second group
      (treatment, n = 30) used toothbrushing supplemented with a 0.4% SnF2 gel used
      twice daily for the entire 18-month study period. Clinical assessments (Plaque
      Index, Gingival Index, bleeding tendency, and coronal staining) were made single
      blind before appliances were placed and 1, 3, 6, 9, 12, and 18 months after
      appliances were placed. Complete data were obtained for 32 control and 23 SnF2
      gel subjects. The results indicated that the SnF2 gel group had significantly
      lower scores for plaque index (p < 0.01), gingival index (p < 0.001), and
      bleeding tendency (p < 0.001) at all examinations than did the control group. In
      the SnF2 group, one subject developed mild coronal staining, and two subjects
      developed moderate staining. We conclude that the use of a 0.4% SnF2 gel
      containing more than 90% available Sn2+ is an effective adjunct to mechanical
      tooth cleaning in preventing gingivitis in adolescents undergoing orthodontic
      treatment with fixed appliances.

PMID- 8291492
TI  - Statistics of differential Lissajous EMG for normal occlusion and Class II
      malocclusion.
AB  - Differential Lissajous electromyography (DL-EMG), a method of representing the
      simultaneous EMG values of two paired muscles as a single, continuous figure, was
      used in chewing tests with a sample of Japanese women having normal occlusion
      compared with a like group of Japanese female adolescents, having Class II,
      Division 1 malocclusion. For the normal sample, the DL-EMG figures described by
      the coordinated activity of the bilateral temporal and masseter muscles during
      chewing gum mastication typically appeared as repetitions of loops. Statistical
      data were gathered on the total EMG voltages, and on the location, rotational
      direction, and orientations of the DL-EMG loops when graphed onto Cartesian
      coordinates. These data were compared with those taken from the Class II sample.
      Significant differences were observed in the latter group for the EMG voltage
      levels of the balancing-side masseter muscles. The DL-EMG figures of the Class II
      group also showed irregularities in the shapes, locations, rotational directions,
      and orientations of the loops, indicative of irregular masticatory patterns.
      These data suggest that with sufficient control of factors such as age and sex,
      electromyography and especially DL-EMG techniques can be useful for
      characterizing masticatory differences between various occlusal groups.

PMID- 8291493
TI  - An investigation into the characteristics of the PG canine retraction spring.
AB  - The forces and couples produced by a model of the PG maxillary canine retraction
      spring (Danish loop) when activated have been derived by using the complementary
      (strain) energy method. The theoretical results of the analysis have been
      verified by experiments on enlarged planar models in a special jig that, by means
      of strain gauges, was capable of recording the forces and couples developed when
      the models were activated. Good agreement between theory and experiment was
      obtained that enabled the analysis to be used with confidence to predict the
      characteristics of clinical-size loops, and to compare the behavior of the PG
      retractor with some other maxillary canine retraction springs.

PMID- 8291494
TI  - Tunnel traction of infraosseous impacted maxillary canines. A three-year
      periodontal follow-up.
AB  - A surgical orthodontic procedure was used to treat deep infraosseous impacted
      canines (test teeth) associated with the persistence of the deciduous tooth in 15
      patients who had the contralateral canine normally erupted (control teeth). The
      periodontal outcome was evaluated at the end of the orthodontic treatment and 3
      years later. After extraction of the deciduous canine, a mucoperiosteal flap was
      raised on the buccal (seven cases) or palatal (eight cases) aspect, to expose the
      cusp of the impacted tooth. The empty socket of the deciduous tooth was extended
      to reach the impacted cusp and to form an osseous tunnel. A chain was passed
      through the tunnel and fixed to a bonded device on the impacted cusp. The flap
      was sutured back into its original position. The chain was used for traction to
      the impacted canine toward the center of the alveolar ridge. No attachment loss
      and no recession were observed at the end of the active therapy or 3 years later.
      No significant differences in keratinized tissue width were observed between test
      and control teeth at the follow-up examination.

PMID- 8291496
TI  - Reflections on our orthodontic heritage.

PMID- 8291495
TI  - Prepubertal trauma and mandibular asymmetry in orthognathic surgery and
      orthodontic patients.
AB  - The association between radiographic evidence of mandibular asymmetry and history
      of prepubertal trauma was analyzed in orthognathic surgery patients and
      orthodontic patients. There were statistically significant associations between
      radiographic evidence of mandibular asymmetry and a history of prepubertal trauma
      in both patient groups. The results suggest that prepubertal trauma could be one
      etiologic factor for the development of mandibular asymmetry.

PMID- 8291497
TI  - The individuality of the patient and the temporomandibular joints. Part I.

PMID- 8291498
TI  - Decades of decision: a changing panorama.

PMID- 8291499
TI  - Determination of the tooth mobility change during the orthodontic tooth movement
      studied by means of Periotest and MIMD (the mechanical impedance measuring device
      for the periodontal tissue).
AB  - Two mechanical devices were selected to attempt to assess any changes in tooth
      mobility when orthodontic force was applied. A Periotest (PT) for assessing
      mobility and a mechanical impedance measuring device (MIMD) were the instruments
      chosen to diagnose the changes in the periodontal condition. The relative
      mobility of four canines after orthodontic tooth movement manipulation was
      assessed over a 4-week period. Both devices were able to detect very small
      changes in tooth mobility and could follow the changes during tooth movement.
      According to the Periotest unit, the tooth mobility changes were not within the
      clinically abnormal range, despite the initial retraction load from a sectional
      arch, applied in a horizontal direction with about 150 gm for each tooth. In all
      instances, the contiguous maxillary first premolar had been removed 1 to 2 months
      before force application. The tooth mobility observed in this investigation could
      be different from that caused by periodontal disease or traumatic injury. Just
      after orthodontic tooth movement manipulation, the Periotest values (PTV), as
      measured on the Periotest, of tooth mobility decreased and the resistance as
      measured by the mechanical impedance measuring device (MIMDM) was increased.
      Thus, initially, there is a greater resistance to movement with decreased
      mobility. After the experimental period of 4 weeks, there was an increase in the
      mobility, as measured by the Periotest and the mechanical resistance decrements
      were observed. However, the Periotest units showed some different changes
      occasionally that did not seem to reflect the state of tooth movement. This needs
      to be investigated further over a longer period of time. On the basis of the
      results obtained, it does appear that it is feasible to use these devices to
      determine mobility changes in patients at various stages of orthodontic
      treatment.

PMID- 8291500
TI  - Glomerular expression and cell origin of transforming growth factor-beta 1 in
      anti-glomerular basement membrane disease.
AB  - The glomerular expression (mRNA levels) of transforming growth factor-beta 1 (TGF
      beta 1) was assessed in two forms of rat anti-glomerular basement membrane (GBM)
      disease, a macrophage-independent and a macrophage-dependent variant. After a
      single intravenous injection of rabbit anti-rat GBM immune serum, significant
      proteinuria and histopathologic changes developed in both variants. Increased TGF
      beta 1 mRNA levels were found in isolated glomeruli of the macrophage-dependent
      variant only in which glomerular infiltration by macrophages also occurred.
      Macrophages isolated from glomeruli of animals with this variant demonstrated TGF
      beta 1 mRNA levels comparable to those found in glomeruli isolated at the same
      time point after injection of the anti-GBM serum. The observations indicate that
      in anti-GBM disease, enhanced glomerular TGF-beta 1 expression occurs in the
      macrophage-dependent variant and suggest that infiltrating macrophages account
      for this event.

PMID- 8291501
TI  - Quantitative assessment of platelet function and clot structure in patients with
      severe coronary artery disease.
AB  - The prothrombotic state of patients with coronary artery disease (CAD) can be
      attributed partially to platelet activity. Management of such patients is
      hindered by a lack of techniques to assess hemostatic function. This study used a
      sensitive technique to monitor platelet function by measuring platelet force
      development during clot retraction. This technique allowed simultaneous
      measurement of clot elastic modulus on the same sample. Fibrin mass-length ratio
      (mu), fibrinopeptide A, D-Dimer, von Willebrand's factor, thromboxane A2,
      platelet aggregation studies, and bleeding times also were performed. Fourteen
      patients with CAD were compared with 10 healthy volunteers. Despite more than 95%
      suppression of thromboxane B2 and prolongation bleeding times in patients taking
      aspirin, force development remained significantly elevated over healthy control
      patients (8,279 +/- 476 dynes versus 4,857 +/- 380 dynes, p < 0.0006). Patients
      not taking aspirin had normal bleeding times and force development of 19,110 +/-
      3,700 dynes. Clot elastic moduli were enhanced in patients with CAD whether
      taking or not taking aspirin. Adenosine diphosphate and ristocetin-induced
      platelet aggregation were insensitive to the effect of aspirin in patients with
      CAD. Fibrinopeptide A, von Willebrand's factor, and D-Dimer levels were
      significantly elevated, and fibrin mass-length ratios were significantly larger
      in patients with CAD. Therefore, despite aspirin therapy, patients with severe
      CAD have evidence of persistent platelet activation and rigid clot structure.
      Monitoring of platelet force development may prove useful in delineating enhanced
      platelet function.

PMID- 8291502
TI  - Transient decrease of binding of insulin to platelets in acute ischemic heart
      disease.
AB  - The specific binding sites of 125I-insulin in platelets from nondiabetic patients
      with acute myocardial infarction and unstable angina pectoris was significantly
      decreased (192 +/- 84/cell) during the acute ischemic condition when compared
      with normal platelets (496 +/- 76/cell; p < 0.001, n = 9). A relatively low mean
      plasma insulin level (20 microU/mL) with an elevated mean glucose level (130
      mg/dL) was noted. The decreased binding of insulin and the relatively low mean
      plasma insulin level during the acute ischemic condition improved into the normal
      range during 8 to 12 weeks of recuperation. The decrease of insulin binding sites
      in the acute phase and their subsequent increase during recovery were directly
      related to the hormone-induced increase in sensitivity to prostaglandin E1
      through the stimulation of adenosine 3',5'-cyclic monophosphate formation in
      platelets by the prostanoid.

PMID- 8291503
TI  - Characterization of a low molecular weight Na-K-ATPase inhibitor of urinary
      origin.
AB  - It has been demonstrated that expansion of extracellular fluid volume induces the
      release of a low-molecular-weight natriuretic and sodium-potassium-activated
      adenosine triphosphatase inhibiting hormone (NKAI). In this study, we used a
      highly purified hormone extracted from pooled hypertensive urines (u-NKAI). Like
      ouabain, this compound was found to be a potent inhibitor of the sodium-potassium
      activated adenosine-triphosphatase and potassium-stimulated paranitrophenyl
      phosphatase enzyme systems as well as a vasoconstrictor in vitro. In contrast to
      ouabain, which is a competitive inhibitor of both enzyme systems with respect to
      potassium, u-NKAI is noncompetitive. Furthermore, u-NKAI differs from ouabain by
      its lack of cross-reactivity with digoxin antibodies. In addition, whereas
      ouabain binds to both high-affinity and low-affinity binding sites on the sodium
      potassium-activated adenosine-triphosphatase enzyme in the absence of potassium,
      u-NKAI binds only to the low-affinity binding sites. This study demonstrates that
      the highly purified u-NKAI, although ouabain-like in certain respects, is not an
      "endogenous ouabain."

PMID- 8291504
TI  - Effect of a simple ambulatory experience on career choice and attitudes of
      medical students.
AB  - Students were allocated randomly to participate in a simple ambulatory experience
      during their third-year medicine clerkship. A convenience sample was surveyed by
      questionnaire in the fall of their fourth year, after decisions were made
      regarding future career plans. The questionnaire assessed medical student
      attitudes toward general internal medicine and career choice. Valuation of the
      effectiveness of the clerkship was associated with choosing a career in internal
      medicine (p = 0.007); having an ambulatory experience was not associated with
      subsequent career choice. Sixty-two percent of all students felt the clerkship
      affected their career choice a great deal or moderately; these students were
      likely to find a career in general internal medicine less attractive as a result
      of their clerkship (p = 0.008). When stratified, this association disappeared in
      those students who participated in the ambulatory experience (p = 0.39) but
      persisted in those who did not (p = 0.01). A simple experience in internal
      medicine clinics during a third-year clerkship was not associated with subsequent
      career choice, but had some positive effects on attitudes toward general internal
      medicine as a career.

PMID- 8291505
TI  - Methods for screening for hearing loss in older adults.
AB  - Two common screening tools for detecting hearing loss, the Hearing Handicap
      Inventory for the Elderly-Screening Version (HHIE-S) and Audioscope, are
      compared. One hundred eighty-five consecutive patients over age 60 at a primary
      care clinic received both screening tests followed by pure tone audiometry. Three
      criteria for hearing loss was considered: Speech Frequency Pure Tone Average > or
      = 25 dB; High Frequency Pure Tone Average > or = 25 dB; and Ventry and
      Weinstein's criteria of a 40 dB loss at 1.0 or 2.0 kHz. Ranges of respective
      operating characteristics for the Audioscope versus the HHIE-S were:
      sensitivities 0.64 to 0.96 versus 0.29 to 0.63; specificities 0.80 to 0.91 versus
      0.75 to 0.93; and positive likelihood ratios 4.86 to 7.52 versus 2.42 to 4.27.
      Most patients preferred screening with the Audioscope (60%) over the HHIE-S
      (13%). The Audioscope is preferred by patients, and outperforms the HHIE-S using
      a variety of reference standard definitions.

PMID- 8291506
TI  - Case report: cardiotoxic calcemia.
AB  - The effects of hypercalcemia on the heart and the resulting alterations of the
      electrocardiogram are well established. However, there are only rare reports of
      arrhythmias caused by hypercalcemia in primary hyperparathyroidism. This article
      describes a case of severe hypercalcemia secondary to hyperparathyroidism causing
      tachy-brady syndrome.

PMID- 8291507
TI  - Case report: transverse myelitis associated with Epstein-Barr virus infection.
AB  - Transverse myelitis is a rare complication of Epstein-Barr virus (EBV) infection.
      This article describes a case of a previously healthy patient with a subacute
      transverse myelopathy. The cerebrospinal fluid showed lymphocytic pleocytosis and
      protein elevation. A magnetic resonance imaging scan demonstrated abnormal spinal
      cord signal intensity over several cervical and thoracic segments, suggesting the
      diagnosis of transverse myelitis. The patient was treated with high-dose
      corticosteroids and had a rapid improvement. Serologic studies for other viruses
      were negative; antibody tests indicated acute EBV infection. It is thought this
      represents a case of transverse myelitis associated with acute EBV infection.
      Although a few similar patients have been reported previously, this case is the
      first where EBV serology suggested the etiology at the time of diagnosis, when
      EBV antibody titers and polymerase-chain reaction for EBV DNA in the
      cerebrospinal fluid were performed, and when a magnetic resonance imaging scan
      was used for diagnosis and follow-up.

PMID- 8291508
TI  - Sotalol: a new agent for the treatment of ventricular arrhythmias.
AB  - Sotalol was developed as a nonselective beta-blocker in the 1960s for the
      treatment of hypertension and later for cardiac risk management after myocardial
      infarction. Extensive research has since well described class III type
      electrophysiologic effects on the repolarization of myocardial fibers. Sotalol
      prolongs and homogenizes ventricular refractoriness, resulting in good
      antifibrillatory/antitachycardia protection. The unique combination of beta
      blockade and antiarrhythmic effects probably will promote sotalol's use in
      postmyocardial infarction patients with ventricular tachycardia and sudden death.
      This article summarizes the pharmacologic and cardiovascular effects of this new
      drug, outlining its clinical use.

PMID- 8291509
TI  - Chenodeoxycholate: the bile acid. The drug. a review.
AB  - Chenodeoxycholate (3 alpha, 7 alpha-dihydroxy-5 beta-cholanic acid) is a primary
      bile acid directly synthesized from cholesterol. It is an amphipathic molecule,
      possessing both a hydrophobic side and a polar hydrophilic side, giving it the
      ability to solubilize lipids in a water environment. Bile acids are necessary for
      the absorption of fats and fat soluble vitamins. Chenodeoxycholate inhibits the
      rate-limiting step of cholesterol synthesis, the formation of hydroxymethyl
      glutaryl-coenzyme A. It was first reported to be useful in the dissolution of
      cholesterol gallstones in 1972. Today, chenodeoxycholate has other medicinal uses
      and is used for the management of cerebrotendinous xanthomatosis,
      hypertriglyceremia, congenital liver diseases, rheumatoid arthritis, and
      constipation. This article details some finer points of chenodeoxycholate
      biochemistry and physiology and discusses in some detail the current and past
      clinical uses of chenodeoxycholate. This is not an exhaustive discussion on
      gallstone dissolution therapies, but an overview of some of the lesser-known uses
      for this drug.

PMID- 8291510
TI  - Southwestern Internal Medicine Conference: brucellosis: don't let it get your
      goat!
AB  - Brucellosis is a highly pleomorphic zoonotic infection caused by one of the
      following four species of gram-negative facultative intracellular coccobacilli:
      Brucella melitensis, B. abortus, B. suis, or B. canis. The disease is a worldwide
      public health problem and a significant cause of economic losses in domestic live
      stock. Although largely eradicated in most industrialized countries, in the
      United States there has been an upsurge of B. melitensis cases associated with
      the ingestion of unpasteurized goat's milk or goat's milk cheese from Mexico.
      Brucellosis can be either insidious or abrupt in onset and can affect virtually
      every organ system; skeletal involvement (spondylitis, arthritis) is the most
      frequent metastatic complication. Cases are diagnosed either by isolation of the
      bacterium (usually from blood) or by serologic testing. Treatment of brucellosis
      requires the administration of two antimicrobial agents. Doxycycline plus
      streptomycin or rifampin or trimethoprim-sulfamethoxazole plus rifampin appear to
      be the most effective regimens.

PMID- 8291511
TI  - A non-cyclo-oxygenase, non-nitric oxide relaxing factor is present in resistance
      arteries of normotensive but not spontaneously hypertensive rats.
AB  - The present experiments tested the hypothesis that decreased production of an
      endothelium-derived relaxing factor in arteries of hypertensive animals
      contributes to impaired endothelium-dependent relaxation. Acetylcholine-induced
      relaxation of freshly isolated spontaneously hypertensive rat (SHR) vessels pre
      contracted with norepinephrine was impaired compared with Wistar-Kyoto rats
      (WKY). 10 microM indomethacin partially normalized the SHR response. Inhibition
      of nitric oxide synthesis with 100 microM nitro-L-arginine methyl ester or 100
      microM NG-monomethyl arginine shifted the acetylcholine relaxation curve to the
      right, but had no effect on the maximal relaxation in WKY and completely
      inhibited relaxation of SHR. A similar pattern was observed with methylene blue
      (0.3 microM). Acetylcholine-induced relaxation of WKY vessels pre-contracted with
      5 microM norepinephrine and 100 mM K+ was attenuated 60% compared with vessels
      pre-contracted with norepinephrine alone, and was completely inhibited by nitro-L
      arginine methyl ester; relaxation of SHR vessels was decreased by 50%. Six-hour
      storage at 37 degrees C significantly attenuated acetylcholine-induced relaxation
      in both strains; treatment with indomethacin improved the response. Moreover,
      relaxation of WKY vessels was completely inhibited by nitro-L-arginine methyl
      ester and NG-monomethyl arginine after the storage period. The absence of L
      arginine-induced relaxation and lack of effect of supplementation with L-arginine
      indicated that the constitutively active NO synthetase was not induced and that L
      arginine substrate was limiting. The results indicate that mesenteric resistance
      arteries of the WKY express a relaxing factor generated by a non-cyclo-oxygenase,
      non-nitric oxide synthetase pathway that is possibly a hyperpolarizing
      factor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291512
TI  - Metacarpophalangeal pattern profile analysis in Brachmann-de Lange syndrome.
AB  - We analyzed the metacarpophalangeal pattern profile (MCPP) of 19 individuals with
      Brachmann-de Lange syndrome (BDLS) and calculated a mean syndrome profile.
      Fourteen of 19 individuals with BDLS had significant positive correlations which
      indicated clinical homogeneity. Discriminant analysis of individuals with BDLS
      compared with a sample of normal individuals produced a correct classification
      rate of 100% based on a function of 2 MCPP variables that may provide a useful
      tool for assisting in the diagnosis of BDLS. An average pattern variability index
      calculated for the BDLS patients was 1.9 indicating an abnormal hand pattern in
      this syndrome.

PMID- 8291513
TI  - Radiological features in Brachmann-de Lange syndrome.
AB  - Brachmann-de Lange syndrome (BDLS) is a well-delineated disorder consisting
      variably of pre- and postnatal growth deficiency, microbrachycephaly,
      characteristic face, hypertrichosis, visceral anomalies, and limb defects
      consisting primarily of variable limb reduction defects, micromelia, and elbow
      abnormalities. The course is usually marked by initial hypertonicity, low-pitched
      weak cry, feeding problems, and behavioral problems with marked mental
      deficiency. In classical cases there is rarely any difficulty in making the
      diagnosis, but for mildly affected cases, it may be difficult to feel secure
      about the diagnosis. In an effort to increase the precision of diagnosis for
      mildly affected cases, we reviewed roentgenograms in 21 cases of Brachmann-de
      Lange syndrome, as well as previously published descriptions of the radiological
      manifestations. Unusual radiologic manifestations were related primarily to the
      limb anomalies, and these were often asymmetric. These manifestations included
      digital abnormalities, which ranged from acheiria to oligodactyly, hypoplasia of
      the thumb and first metacarpal, clinodactyly of the fifth finger, or
      ectrodactyly. Long bone abnormalities included ulnar a/hypoplasia, dysplasia of
      the radial head, or fusion of the elbow. When there was a single forearm bone,
      there was often fusion at the elbow and oligodactyly, which made it difficult to
      determine whether the radius or ulna was absent. Other radiologic manifestations
      included 13 ribs with precocious sternal fusion, and micrognathia. We suggest
      that these radiologic manifestations could increase diagnostic precision in
      mildly affected cases.

PMID- 8291514
TI  - Hemimelia in Brachmann-de Lange syndrome (BDLS): a patient with severe deficiency
      of the upper and lower limbs.
AB  - We report on a male infant with Brachmann-de Lange syndrome (BDLS) and ulnar
      hemimelia and monodactyly but also absence of both tibiae, the right distal femur
      being bifurcated. One similar observation was published earlier. The question is
      raised whether these malformations are coincidental or a rare component of BDLS.

PMID- 8291515
TI  - Congenital diaphragmatic hernia in the Brachmann-de Lange syndrome.
AB  - We present 12 children with typical Brachmann-de Lange syndrome and congenital
      diaphragmatic hernia. Affected children were more likely to be of low birth
      weight and to have major upper limb malformations. Hernia repair was attempted in
      4 of these children, and only one survived past 12 months. Newborn infants with
      congenital diaphragmatic hernia should be examined carefully for evidence of the
      Brachmann-de Lange syndrome because diagnosis of this condition may influence
      their clinical management and prognosis.

PMID- 8291516
TI  - Prenatal diagnosis of congenital diaphragmatic hernia not amenable to prenatal or
      neonatal repair: Brachmann-de Lange syndrome.
AB  - Brachmann-de Lange syndrome (BDLS) is a variable multiple congenital anomaly
      syndrome that occasionally includes congenital diaphragmatic hernia (CDH). CDH
      per se is commonly diagnosed antenatally and has been corrected with increasing
      success in utero and by neonatal repair with extracorporeal membrane oxygenation
      (ECMO). In utero repair requires normal karyotype as well as the absence of other
      lethal anomalies. Postnatal repair in combination with ECMO has resulted in
      improved neonatal outcome and has been recommended in all cases not having in
      utero repair. We describe a fetus diagnosed with a diaphragmatic hernia at 18
      weeks of gestation in a woman whose only other pregnancy has been a 16 week
      abortus diagnosed with Fryns syndrome (FS). FS is a lethal, variable congenital
      anomaly syndrome that includes CDH, which is thought to contribute to the
      lethality of the syndrome. In utero repair was considered, but rejected because
      of the position of the liver and suspected FS. The patient elected to carry the
      pregnancy to term. Postnatal repair with ECMO was considered; however, the infant
      died at several hours of age because of severe pulmonary hypoplasia, being
      considered ineligible for ECMO. The diagnosis of BDLS was made at autopsy and
      suggests that the first case may, in fact, have been BDLS. In spite of recent
      success in the repair of CDH both in et ex utero, CDH in association with BDLS is
      likely lethal, and women with fetuses diagnosed antenatally with CDH and BDLS
      should be counseled as such.

PMID- 8291517
TI  - Diaphragmatic defect in Brachmann-de Lange syndrome: a further observation.

PMID- 8291518
TI  - Occurrence of the Sandifer complex in the Brachmann-de Lange syndrome.
AB  - Gastroesophageal reflux is a common occurrence in infancy. The most severe
      complications of reflux include torticollis, opisthotonus, and paroxysmal
      dystonic posture (known as the Sandifer complex). We examined 17 patients now
      ranging in age from 9 months to 19 years (mean age 11 years) with the Brachmann
      de Lange syndrome for evidence of gastroesophageal reflux and found that 13 had
      not only reflux, but also posturing and behavior consistent with the Sandifer
      complex. We propose that early recognition of gastroesophageal reflux in these
      patients may prevent the full picture of the Sandifer complex and allow for
      medical treatment rather than surgical intervention.

PMID- 8291519
TI  - Gastrointestinal abnormalities: a significant cause of feeding difficulties and
      failure to thrive in Brachmann-de Lange syndrome.
AB  - Gastroesophageal abnormalities occur with increased frequency in patients with
      Brachmann-de Lange syndrome (BDLS) and contribute to problems with feeding,
      emesis and failure to thrive. Comprehensive evaluation including longitudinal
      assessment of growth and development of 8 patients with BDLS was performed.
      Clinically significant feeding problems occurred in 6 of the 8 patients and the
      affected children were subsequently evaluated for gastrointestinal abnormalities.
      Findings in these patients included tracheal aspiration, esophageal dysmotility,
      gastroesophageal reflux, hiatal hernia, and esophagitis. Medical treatment was
      instituted where appropriate, and surgical treatment was performed if the
      problems did not resolve with medical treatment. Improvement in weight centiles
      occurred in all patients fed by nasogastric or feeding gastrostomy tube but only
      one patient appeared to experience increase in rate of linear growth. Careful
      monitoring of symptoms and growth parameters, and prompt institution of
      appropriate medical and surgical measures can improve the health and physical
      outcome of many patients with BDLS.

PMID- 8291520
TI  - Fetal biometry in the Brachmann-de Lange syndrome.
AB  - The Brachmann-de Lange syndrome (BDLS) is diagnosed in children on the basis of a
      distinctive clinical phenotype which includes retarded physical growth. Because
      there are no genetic or biochemical tests at present, the antenatal detection of
      the syndrome may depend upon identification of some aspect of the phenotype in
      the fetus using ultrasound imaging. We studied the growth of 23 subsequently
      diagnosed fetuses with the BDLS using standard biometric parameters defined by
      prenatal ultrasound imaging. Sonographic studies were obtained through a national
      parents' group, the Cornelia de Lange Syndrome Foundation. Assessment of fetal
      growth was made using four standardized measurements: the biparietal diameter,
      head circumference, femur length, and abdominal circumference. These values were
      compared to established tables of normal fetal growth and established ratios of
      fetal body proportions. The cross-sectional growth curve derived using all
      measurements collected as a composite group indicates that growth retardation
      would be first detected as early as 25 weeks. In five fetuses with measurements
      both before and after 25 weeks of gestation, longitudinal growth curves indicated
      that the diagnosis of "small for gestational age" would have been suggested
      between 20 and 25 weeks. The mean fetal weight estimates closely followed the
      fifth centile curve of normal fetuses both before and after 25 weeks. Cephalic
      indices in BDLS fetuses indicated either frank brachycephaly (25%), or were at
      the upper portion of the normal range. Femur lengths were relatively short (less
      than 90% of their expected length) ion 4 of the 11 fetuses where such information
      could be obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291521
TI  - Growth manifestations in the Brachmann-de Lange syndrome.
AB  - We have obtained serial measurements on 180 patients with clinically confirmed
      Brachmann-de Lange syndrome (BDLS) in order to derive standard growth curves. The
      patients were evaluated in our genetics department and through meetings of the
      Cornelia de Lange Syndrome Foundation, a support group for families of affected
      individuals. The data were obtained from the records of pediatricians, other
      physicians, schools and parents, as well as from personal examination on each of
      these patients at least once, often periodically. The growth curves include
      height, weight and head circumference measurements from birth through adulthood.
      Prenatal growth and birth weights are below the 5th centile in most (68%) cases,
      with an average birth weight of 2,277 g. Growth persists below the normal curves
      in most of the patients throughout life. Height velocity is equal to the normal
      range but there is slower pubertal growth. Weight velocity is below the normal
      range throughout life until late adolescence. Average head circumference remains
      below the second centile. Thin body habitus coupled with slow growth and
      proportionate small stature is a manifestation of the syndrome, but is commonly
      mistaken for failure to thrive.

PMID- 8291522
TI  - Physical growth in Brachmann-de Lange syndrome.
AB  - Growth in 30 patients with Brachmann-de Lange syndrome (BDLS) was evaluated and
      found to be deficient in 27/30, with 17/27 having intrauterine growth retardation
      (IUGR). In 12/27 patients, endocrine evaluations have been completed. Seven of 12
      were normal and 4/12, one with empty sella, had "classical" growth hormone
      deficiency with extreme short stature, markedly delayed skeletal maturation and
      subnormal growth hormone secretion in response to provocative stimuli. One of 12
      patients had discordance between insulin growth factor I levels and growth
      hormone responses to insulin and clonidine suggestive of end organ resistance to
      growth hormone. It appears that the hypothalamic-pituitary function is
      compromised in at least some BDLS patients. Thus, endocrine evaluations are
      warranted for the patients with short stature.

PMID- 8291523
TI  - Survey of speech and language skills with prognostic indicators in 116 patients
      with Cornelia de Lange syndrome.
AB  - Speech and language evaluations of 116 patients, ages 2 months to 29 years, with
      Cornelia de Lange syndrome (CdLS), also known as Brachmann-de Lange syndrome,
      were conducted to survey speech and language skills and to ascertain the
      prognostic value of related variables. These patients were evaluated at
      conferences of the CdLS Foundation. The data from these evaluations were then
      analyzed using the database program of Paradox 3.5. The findings indicated that
      53% of the children who were 4 years or older combined 2 or more words into
      sentences and 33% had no words or only 1-2 words. Four percent were judged to
      have language skills within normal to low-normal limits. Children who were not
      talking at all or who were severely delayed in language skills had at least one
      of the following characteristics: birth weight under 5 lbs.; a reported diagnosis
      of moderate-to-severe hearing impairment; upper limb malformations; poor
      abilities to relate socially; and/or severe motor delays, e.g., they did not sit
      up until after age 25 months or did not walk until after 35 months.

PMID- 8291524
TI  - Familial Brachmann-de Lange syndrome: further evidence for autosomal dominant
      inheritance and review of the literature.
AB  - We report on a mother and daughter with the Brachmann-de Lange syndrome which
      supports the view that in some families this disorder is due to autosomal
      dominant inheritance. A review of the literature concerning autosomal and
      recessive inheritance of this syndrome is presented.

PMID- 8291525
TI  - Partial duplication of 3q (q25.1-->q26.1) without the Brachmann-de Lange
      phenotype.
AB  - Partial duplications of chromosome 3 have previously been reported to have
      phenotypic characteristics similar to Brachmann-de Lange syndrome (BDLS). We
      present the case of a 13-year-old girl with an apparent duplication in the 3q25.1
      ->q26.1 region but none of the manifestations commonly seen in BDLS. The
      chromosome 3 duplication was confirmed with a FISH painting probe of the involved
      region. These results suggest that the region critical for Brachmann-de Lange
      syndrome is not within the duplicated region of 3q25.1-->q26.1.

PMID- 8291526
TI  - Asymmetric and symmetric long bone bowing in two sibs: an apparently new bone
      dysplasia.
AB  - We describe 2 sibs, one with congenital asymmetric long bone bowing and one with
      congenital symmetric long bone bowing. Other bony abnormalities in these sibs
      include beaten metal appearance of the skull, dolichomacrocephaly, ocular
      hypertelorism, and anterior beaking and bone-within-bone appearance of vertebrae.
      A differential diagnosis including campomelic dysplasia, kyphomelic dysplasia,
      hypophosphatasia, Grant syndrome, and osteogenesis imperfecta, and a discussion
      of potential mechanisms of long bone bowing are presented. The condition that
      these sibs have shares some characteristics of the above bone disorders, but
      appears to be a separate entity which to our knowledge has not been described
      previously.

PMID- 8291527
TI  - DiGeorge anomaly with renal agenesis in infants of mothers with diabetes.
AB  - We report on 2 infants with the DiGeorge anomaly born to diabetic mothers treated
      with insulin. Both infants had unilateral renal agenesis. One of the mothers has
      manifestations suggestive of velo-cardio-facial syndrome (VCFS). Cytogenetic
      studies on both patients and the mother with apparent VCFS were normal. Molecular
      studies utilizing probes from the DiGeorge critical region did not demonstrate a
      22q11 microdeletion in either patient or the mother with apparent VCFS. We
      conclude that maternal diabetes is a pathogenetic factor in the DiGeorge anomaly,
      and infants of diabetic mothers who have this anomaly should also be screened for
      renal agenesis.

PMID- 8291528
TI  - Syndrome of infantile osteopetrosis and Hirschsprung disease in seven children
      born to four consanguineous unions in two families.
AB  - Two cases of Hirschsprung disease associated with infantile osteopetrosis are
      reported in 2 consanguineous families living in the same area. Both died early.

PMID- 8291529
TI  - Lethal bone dysplasia in a fetus with manifestations of atelosteogenesis I and
      Boomerang dysplasia.
AB  - Atelosteogenesis I (AT-I) and Boomerang dysplasia have been described as separate
      lethal bone dysplasias. The possibility of a common cause of both conditions was
      suggested by Hunter and Carpenter (Clin Genet 39(6): 471-480, 1991) in their
      report of a patient with apparent manifestations of both AT-I and Boomerang
      dysplasia. We report on a male fetus of 31 weeks gestation whose clinical,
      radiologic and histologic findings are compared to reported cases of AT-I,
      Boomerang dysplasia and the patient of Hunter and Carpenter (Clin Genet 39(6):
      471-480, 1991). From the documentation of clinical and radiologic findings we
      demonstrate overlap of AT-I and Boomerang dysplasia in our patient, and, from
      histologic examination, suggest a defect of cartilage and bone formation as the
      basic abnormality in this lethal bone dysplasia.

PMID- 8291530
TI  - Limb deficiencies, chorion villus sampling, and advanced maternal age.
AB  - Record linkage between a prenatal diagnosis register and a congenital
      malformation register in the state of Victoria, Australia, has enabled further
      evaluation of the suggested association between limb deficiencies and early
      chorion villus sampling (CVS). We found 3 anomalies in this category after later
      CVS (i.e., 9 weeks and beyond), but our data suggest that advanced maternal age
      may be a risk factor for both terminal and all limb deficiencies. The data from
      Victoria are tabulated with data obtained from other registers. Different birth
      prevalence figures are obtained by different registers, therefore limiting
      comparisons between registers.

PMID- 8291531
TI  - Autopsy findings in a severely affected infant with a 2q terminal deletion.
AB  - We describe a 37-week gestation female infant who was born with a terminal 2q
      deletion. Both of her parents had normal chromosomes. This infant had multiple
      anomalies, including hypertelorism, short palpebral fissures, microphthalmia,
      cleft lip/cleft palate, and abnormal ears. Autopsy documented Dandy-Walker
      malformation with severe hydrocephalus, aortopulmonary window, secundum atrial
      septal defect, duodenal atresia, incomplete rotation of the bowel, gonadal
      dysgenesis, uterus didelphys, and musculoskeletal defects. Compared with the
      other 6 children with 2q terminal deletion documented in the literature, this
      patient is the most severely affected. This patient is also the only one
      documented to have died and undergone autopsy examination. The findings in this
      case provide more data for the eventual description of a "terminal 2q deletion
      syndrome" and suggest that some abnormalities, such as gonadal dysgenesis, may be
      present in living children with this chromosome abnormality.

PMID- 8291532
TI  - Roberts syndrome: a review of 100 cases and a new rating system for severity.
AB  - Roberts syndrome (RS) is a rare genetic disorder characterized by pre- and
      postnatal growth retardation, limb defects, and craniofacial anomalies. Affected
      persons have varying degrees of malformations involving symmetric reduction in
      the number of digits, and length or presence of bones in the arms and legs.
      Craniofacial malformations involve hypertelorism, hypoplastic nasal alae, and a
      high incidence of cleft lip and palate. Familial and sporadic cases have been
      reported consistent with an autosomal recessive mode of inheritance. Mitotic
      cells from many individuals with RS display a characteristic cytogenetic
      phenomenon consisting of repulsion of heterochromatic regions near centromeres,
      particularly of chromosomes 1, 9, 16, and splaying of the short arms of the
      acrocentrics and of the distal Yq. Mitosis in RS cells is abnormal in metaphase
      duration and anaphase progression. Specifically, anaphase figures show a higher
      degree of chromosomes that are outlying, lagging, or prematurely advancing toward
      the poles compared to normal controls. RS cells have abnormal nuclear morphology
      and also show a higher frequency of micronucleation than normal cells, presumably
      as a result of the abnormal mitotic events during anaphase. Therefore, RS has
      been interpreted as a human mitotic mutation syndrome which leads to secondary
      developmental defects. This report reviews 100 cases of RS, summarizes the
      phenotypic, genetic, cytogenetic, and cell biology findings in Roberts syndrome,
      and introduces the RS Rating for quantitating severity.

PMID- 8291533
TI  - Isolation of a yeast artificial chromosome contig spanning the X chromosomal
      translocation breakpoint in a patient with Rett syndrome.
AB  - Rett syndrome is a neurodevelopmental disorder observed exclusively in females. A
      de novo X;3 translocation was detected in a patient (TH) with Rett syndrome. The
      X chromosomal breakpoint maps to Xp21.3 between the distal end of the Duchenne
      muscular dystrophy (DMD) gene and the DXS28 (C7) locus. To determine if this
      translocation caused the Rett syndrome in this patient, our efforts focused on
      mapping and cloning of the X chromosomal breakpoint in this patient. Toward these
      goals, we generated a set of radiation-reduced hybrid cell lines for the short
      arm of the X chromosome to use as a source for region-specific markers. Using Alu
      PCR, 13 new DNA markers were isolated from a radiation-reduced hybrid, which
      retained both DMD and DXS28. These markers were localized within Xp21 using DNA
      from males with various interstitial deletions in this region. Two new markers,
      K23-2p and K23b-1, were found to be closer flanking markers to the X chromosomal
      breakpoint than DMD and DXS28. Long range restriction mapping using K23-2p and
      K23b-1 determined that the maximum distance between them was 800 kb. Several of
      the new markers were developed into sequence tagged-sites and were used to
      isolate yeast artificial chromosome (YAC) clones. A total of 22 YAC clones was
      isolated and characterized; these YACs were then developed into 3 large contigs
      in the Xp21.3 region. This effort resulted in the cloning of the region
      containing the X chromosomal translocation breakpoint of the Rett syndrome
      patient in a 170-kb YAC clone.

PMID- 8291535
TI  - Transverse limb deficiency, oro-mandibular limb hypogenesis sequences, and
      chorionic villus biopsy: human and animal experimental evidence for a uterine
      vascular pathogenesis.

PMID- 8291534
TI  - Report on two patients with Costello syndrome and sialuria.
AB  - We report on 2 unrelated patients with Costello syndrome. The first is a 5-year
      old girl with "coarse" face, nasal papillomata, redundant skin of feet and hands,
      hyperextensible hand and finger joints, curly hair, feeding problems due to oral
      motor apraxia, growth and psychomotor retardation. The second is a 3-year-old boy
      with "coarse" face, loose skin on hands and feet, curly hair, oral motor apraxia,
      severe growth and psychomotor retardation. In both patients urine sialic acid
      levels were found to be repeatedly high. The meaning of this biochemical
      abnormality is discussed.

PMID- 8291536
TI  - Interstitial deletion in chromosome 1: assignment of the breakpoints.

PMID- 8291537
TI  - de Lange syndrome: a clinical review of 310 individuals.
AB  - Three hundred ten individuals with a clinical diagnosis of de Lange syndrome were
      seen and examined in conjunction with the parent support group. One hundred
      thirty-four males and 176 females whose ages ranged from birth to 37 years made
      up the study group. Examination findings were recorded for those features
      described by de Lange in her original report of the syndrome to determine the
      frequency and significance of each. In addition, questionnaires were completed by
      128 of these families and medical, growth and developmental records were
      collected. The clinical diagnosis seems best supported by the facial features of
      the syndrome including the long eyelashes and confluent eyebrows (synophrys),
      although additional characteristics are needed. Only 27% had the upper limb
      deficiencies commonly associated with the syndrome. Growth was retarded in nearly
      all individuals, often of prenatal onset. Medical problems occurred frequently
      and most often involved the eye and ear, as well as the cardiac and
      gastrointestinal systems. Of 14 deaths, almost half were secondary to cardiac or
      gastrointestinal complications. The recurrence risk in 377 sibs of the patients
      was calculated to be less than 1%. Although development lagged significantly in
      speech, most individuals developed good self-help skills. The study demonstrated
      a higher proportion of patients affected mildly with the syndrome than is
      commonly appreciated. This underscores the importance of early recognition and
      appropriate medical and developmental support.

PMID- 8291538
TI  - Clinical variability within Brachmann-de Lange syndrome: a proposed
      classification system.
AB  - Seven patients, including two sibs, with the Brachmann-de Lange syndrome (BDLS)
      are presented as representative of the different types of BDLS in a proposed
      classification system. Type I ("classic") patients have the characteristic facial
      and skeletal changes of BDLS using the criteria in the diagnostic index of Preus
      and Rex. Type I is distinguished from the other subtypes by prenatal growth
      deficiency (< 2.5 S.D. below mean for gestation) becoming more severe postnatally
      (< 3.5 S.D. below the mean), moderate to profound psychomotor retardation, and
      major malformations which result in severe disability or death. Type II ("mild")
      BDLS patients have similar facial and minor skeletal abnormalities to those seen
      in type I; however, these changes may develop with time or may be partially
      expressed. Patients with type II BDLS are distinguished from those with other
      types by mild to borderline psychomotor retardation, less severe pre- and
      postnatal growth deficiency, and the absence of (or loss severe) major
      malformations. Behavioral problems can be a significant clinical problem in type
      II BDLS. Type III ("phenocopies") BDLS includes patients who have phenotypic
      manifestations of BDLS which are causally related to chromosomal aneuploidies or
      teratogenic exposures.

PMID- 8291539
TI  - Brachmann-de Lange syndrome. Delineation of the clinical phenotype.
AB  - A total of 31 cases previously diagnosed as having Brachmann-de Lange syndrome
      were ascertained and examined, of which 11 were thought to have been
      misdiagnosed. Of those correctly diagnosed, there appeared to be a phenotypic
      dichotomy with classical and mild cases. Those facial findings of greatest
      diagnostic value were the combination of the characteristic eyebrows, long
      philtrum, thin lips and crescent-shaped mouth. The characteristic eyebrows were
      neat, well defined and arched as though they had been pencilled. This combination
      of anomalies was absent in postpubertal males but not in postpubertal females.
      Facial abnormalities most likely to lead to incorrect use of the eponym were
      hypertrichosis, synophrys, and bushy eyebrows.

PMID- 8291540
TI  - Variability of the Brachmann-de Lange syndrome.
AB  - Brachmann-de Lange syndrome (BDLS) is a relatively common multiple congenital
      anomaly/mental retardation syndrome, whose cause is unknown. The clinical
      variability of this condition is well-known. Recently some reports suggested the
      possible existence of a mild BDLS phenotype. We report on 30 patients in whom a
      diagnosis of BDLS was made or strongly suspected in 12 different Italian
      hospitals. Based on clinical evaluation we divided them into two groups,
      classical and mild BDLS cases. We compare the clinical data of these patients and
      we discuss the problems which arise in trying to define clear criteria of
      distinction between these two groups.

PMID- 8291541
TI  - On the variability of the Brachmann-de Lange syndrome in seven patients.
AB  - The results of the clinical and radiographic study of 7 patients support the view
      of a unimodal and rather narrow phenotypic spectrum in the Brachmann-de Lange
      syndrome (BDLS) and reject the existence of a "classic" type of patient and a
      "mild phenotype" without upper limb defects who survive with moderate to severe
      mental retardation. Similarity among all patients is greater than their
      phenotypic differences. Strict clinical definition of the syndrome warrants
      easier access to the still unknown cause, most probably a single gene mutation
      with autosomal dominant inheritance.

PMID- 8291542
TI  - Mild mental retardation with classic somatic phenotype in the Brachmann-de Lange
      syndrome.
AB  - Severe mental retardation is the most handicapping disability for individuals
      with Brachmann-de Lange syndrome (BDLS). Reports of higher functioning patients
      with suspected BDLS have invariably described those with a "mild" BDLS somatic
      phenotype. Here we report on 2 high-functioning females, ages 3.7 and 10.6 years,
      with the classic BDLS somatic phenotype, i.e., all growth parameters at 4-5
      standard deviations below the mean prenatally and postnatally. These 2 patients
      serve to extend the spectrum of classic BDLS to include cognitive function in the
      mild-to-moderate range of mental retardation.

PMID- 8291543
TI  - Brachmann-de Lange syndrome with normal IQ.
AB  - The Brachmann-de Lange syndrome is a disorder with a high degree of clinical
      variability, generally associated with moderate to severe mental retardation. To
      date, 7 previous cases of Brachmann-de Lange syndrome with normal intelligence
      (IQ > 70) have been described. We report the eighth case of Brachmann-de Lange
      syndrome with normal intelligence. In reviewing the literature, consistent
      clinical manifestations seen in these 8 patients that are of prognostic value are
      the absence of significant limb anomalies and birth weight > 2,500 g.

PMID- 8291544
TI  - Brachmann-de Lange syndrome: diagnostic difficulties posed by the mild phenotype.
AB  - We describe 4 patients with facial changes of Brachmann-de Lange syndrome but
      without limb defects. Mental retardation ranged from moderate to severe and the
      degree of prenatal and postnatal growth deficiency was variable. These patients
      exemplify the diagnostic difficulties and counseling dilemmas posed by the mild
      Branchmann-de Lange phenotype. The relationship of the mild phenotype to the full
      syndrome will not be understood until the pathogenetic or causal factor(s) are
      delineated.

PMID- 8291545
TI  - Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) associated with
      interstitial deletion of band 3q22: review and gene assignment to the interface
      of band 3q22.3 and 3q23.
AB  - We report on a child with blepharophimosis, ptosis, and epicanthus inversus
      (BPES), developmental delay and an interstitial deletion of band q22 of
      chromosome 3. A review of chromosome 3q anomalies associated with eye
      abnormalities, specifically blepharophimosis and ptosis, strongly suggests that a
      locus for eyelid development is present at the interface of bands 3q22.3 and
      3q23.

PMID- 8291546
TI  - Najjar syndrome revisited.
AB  - We describe 2 brothers with cardiomyopathy and hypergonadotropic hypogonadism and
      conclude that this is the first description of the Najjar syndrome in the United
      States. The inheritance may be autosomal recessive.

PMID- 8291547
TI  - Characterization of a small supernumerary ring X chromosome by fluorescence in
      situ hybridization.
AB  - We report on a male with mild learning disabilities who has a supernumerary
      marker chromosome. The marker chromosome was defined by fluorescence in situ
      hybridization as a ring X chromosome with breakpoints in the juxacentromeric
      region. Replication studies suggest that the ring X is late-replicating. However
      XIST, a gene in the X inactivation centre interval which is expressed exclusively
      from the inactive X chromosome, is not present on the marker, nor is it expressed
      in the patient's cells. These results are discussed with respect to karyotype
      phenotype correlations and X inactivation.

PMID- 8291548
TI  - Holoprosencephaly and primary craniosynostosis: the Genoa syndrome.
AB  - We report on 2 sibs with holoprosencephaly of the semilobar type, unusual facial
      appearance not diagnostic of holoprosencephaly, and primary craniosynotosis
      involving the coronal and lambdoid sutures. The condition represents a newly
      recognized syndrome, possibly having autosomal recessive inheritance.

PMID- 8291549
TI  - Familial occurrence of agonadism and multiple internal malformations in
      phenotypically normal girls with 46,XY and 46,XX karyotypes, respectively: a new
      autosomal recessive syndrome.
AB  - We report on 2 phenotypic sisters, one with 46,XY; the other with 46,XX. The 2
      girls had similar related internal malformations, including agonadism, hypoplasia
      of the right pulmonary artery, hypoplasia of the right lung, isolated
      dextrocardia with complex vitium cordis, and diaphragmatic hernia (only sib 1) or
      omphalocele (only sib 2). This combination of malformations did not fit into any
      of the previously described syndromes. For this syndrome we suggest the acronym
      PAGOD ([hypoplasia of the] pulmo, and pulmonary artery, agonadism,
      omphalocele/diaphragmatic defect, dextrocardia). The occurrence of a basically
      similar set of malformations in 2 unlike sex is interpreted as evidence for
      autosomal recessive inheritance. The different gonosomal status excludes the Y
      chromosome as a responsible factor. The peculiar finding of a 46,XX sex
      chromosome constitution combined with agonadism and an intact urogenitral tract
      emphasizes the concept of secondary regression of Wolffian and Mullerian
      structures. The associated malformations of mesodermal structures can be
      interpreted as midline defects. We suggest that, from the developmental field
      perspective, secondary regression of midline structures including the gonadal
      anlage explains the pathogenesis reasonably well.

PMID- 8291550
TI  - Prenatal diagnosis and clinical findings in a case of hexasomy 12p.
AB  - We report the first case of hexasomy 12p mosaicism due to 2 copies of an apparent
      i(12p) [46,XX/48,XX, +i(12p), +i(12p)]. In every cell that contained the i(12p),
      2 copies of the marker were found. The hexasomy was found in amniocytes (16%) and
      skin fibroblasts (95%) but not in peripheral blood lymphocytes. The chromosomal
      origin of the marker was confirmed with the use of in situ hybridization of alpha
      satellite specific for the centromere of chromosome 12. The present case was
      diagnosed following chromosome analysis for anomalies on ultrasound. The hexasomy
      12p patient showed striking phenotypic similarities with severely affected
      tetrasomy 12p cases and died shortly after birth. We propose that the more severe
      presentation of this case is due to the 4 extra copies of 12p.

PMID- 8291551
TI  - Adams-Oliver syndrome: a case with juvenile chronic myelogenous leukemia and
      chylothorax.
AB  - We report on a patient with Adams-Oliver syndrome and report new findings: a
      chylous pleural effusion and juvenile chronic myelogenous leukemia. Also, our
      patient had congenital heart disease, confirming that heart lesions are a
      manifestation in this syndrome. The major manifestations of this disorder are
      summarized. Included are cases not previously recognized as having Adams-Oliver
      syndrome identified in a literature survey. Distal limb deficiency is commonest
      with more frequent and more severe involvement of the lower limbs. Scalp defects
      are the second commonest manifestation, while an underlying skull defect is not
      infrequent. Cutis marmorata telangiectatica and dilated scalp veins are
      significant signs of this condition. This review highlights unresolved questions
      about Adams-Oliver syndrome.

PMID- 8291552
TI  - Banding resolution of human chromosomes: a method of accuracy and simplicity.
AB  - Methods of estimating chromosome band resolution have been published but their
      accuracy has not been established. Banding resolution was determined by 4 methods
      which included a computerized linear correlation, the sum of bands on chromosomes
      1 and 2, interpolation of the number of bands on chromosome 10, and interpolation
      of the number of bands on chromosomes 1p, 10, 11p, 12q, and X. The sum of bands
      on chromosomes 1 and 2 multiplied by 6 is the most accurate and simple. The use
      of a simple and reliable method is important for cytogenetic laboratories to
      document quality assurance of routine chromosome analyses, to enhance the
      exchange of information between laboratories, and to establish criteria for
      appropriate band resolution for specific types of specimens.

PMID- 8291553
TI  - Oral involvement of recessive dystrophic epidermolysis bullosa inversa.
AB  - The inversa subtype of autosomal recessive dystrophic epidermolysis bullosa (EBDR
      I) is a rare variant characterized by lesions involving primarily the flexural
      areas of the body. The purpose of this investigation was to characterize the oral
      manifestations of this unusual dermatologic condition. Ten individuals having
      EBDR-I were evaluated and compared with an age and sex-matched population of
      unaffected individuals that served as controls. The diagnosis of EBDR-I was
      confirmed by skin biopsy that demonstrated tissue separation below the lamina
      densa and the clinical presentation of blister formation that typically localized
      to flexural areas. There was clinical variability in the severity and
      distribution of skin involvement; however, none of the affected individuals
      demonstrated pronounced digital webbing, severe generalized blistering or growth
      retardation characteristic of the Hallopeau-Siemens form of EBDR. Oral
      involvement was seen in all cases with ankyloglossia, loss of tongue papillae and
      obliteration of the oral vestibule between the lips and gingiva being typical.
      The oral opening was significantly reduced in older EBDR-I individuals compared
      with matched controls, confirming that acquired microstomia is a characteristic
      of EBDR-I. The teeth were not clinically abnormal or malformed and showed no
      evidence of generalized enamel hypoplasia. Despite this, the prevalence of dental
      caries in EBDR-I individuals was significantly higher than the control group. The
      inversa form of EBDR presents with oral findings that are similar but generally
      milder than those seen in the Hallopeau-Siemens variant of EBDR.

PMID- 8291554
TI  - Malformations and deformations in abdominal pregnancy.
AB  - Abdominal gestation is a relatively uncommon complication of pregnancy. Previous
      reports describe a high incidence of fetal deformations and mortality as well as
      maternal mortality. A case of twin abdominal gestation is presented and the
      literature concerning abdominal pregnancy since 1809 is reviewed. The survival
      rate of liveborn infants of 30 or more weeks gestation was 63%. The maternal
      mortality rate since 1809 was 18.2%, but this has decreased to 4.5% during the
      last 20 years. The combined rate of malformations and deformations in the infants
      was 21.4%. The most common deformations observed were facial and/or cranial
      asymmetry and various joint abnormalities. Among the most common malformations
      were limb deficiency and central nervous system malformations. Proposed
      mechanisms of compression and vascular disruption are discussed.

PMID- 8291555
TI  - Significance of mosaic isochromosome 20q on amniocentesis.
AB  - We report on 2 fetuses with prenatally diagnosed mosaic isochromosome 20q in
      amniotic fluid. Neither had an identifiable cytogenetic abnormality after birth.
      One infant developed a benign intracranial dermoid cyst at age 8 months. The
      other was completely normal in all respects. We are aware of 13 fetuses with this
      prenatally diagnosed chromosome finding; all fetuses tested have had normal
      chromosomes on subsequent cytogenetic studies and all, except one, have been
      morphologically normal. Fetuses with mosaic isochromosome 20q identified on
      amniocentesis are most likely to be phenotypically and cytogenetically normal
      after birth.

PMID- 8291556
TI  - Inverted duplication of chromosome 5p14p15.3 confirmed with in situ
      hybridization.
AB  - Duplication of the short arm of chromosome 5 [dup(5)(p13.1p15.3)] has been
      associated with craniofacial malformations, cardiac defects, renal and intestinal
      malformations, limb abnormalities, and mental retardation. We report a 2-year-old
      white girl with a de novo 46,XX,inv dup(5)(p14p15.3) chromosome constitution, who
      presented with motor and language delays, bilateral strabismus, small posteriorly
      angulated ears, a high-arched palate, mild hypotonia, and an atrial septal
      defect. A CT scan of the head was normal. In situ hybridization with a cosmid
      probe specific for sub-band 5p15.3 (Oncor, Inc., Gaithersburg, MD) was used to
      identify the origin and orientation of the extra material. The milder
      manifestations in our patient are consistent with the hypothesis that significant
      phenotypic effects are associated with duplication of material proximal to band
      5p14. This study demonstrates the usefulness of in situ probes in identifying the
      origin and orientation of duplicated genetic material.

PMID- 8291557
TI  - Association between "plagiocephaly" and hemifacial microsomia.
AB  - Fifteen of 155 patients with hemifacial microsomia were noted to have frontal
      plagiocephaly. These patients were examined to determine whether the frontal
      flattening was either secondary to deformation, the result of unilateral coronal
      synostosis, or part of the spectrum of hemifacial microsomia. The patients were
      categorized as having deformational versus synostotic frontal plagiocephaly by
      documenting position of the supraorbital rims, nasal root, ears, malar eminences,
      chin point, and the palpebral fissure height. Other extracraniofacial anomalies
      were also noted. Fourteen of 15 (93%) patients had characteristic deformational
      abnormalities. Only 1/15 (7%) had an elevated orbit, suggestive of unilateral
      coronal synostosis, but this diagnosis was not radiographically confirmed.
      Frontal deformational plagiocephaly was ipsilateral to the side predominantly
      affected by hemifacial microsomia in all but one patient. Patients with
      hemifacial microsomia-deformational frontal plagiocephaly often had ipsilateral
      torticollis, cervical spine abnormalities, and anomalies outside the craniofacial
      region. This was in contrast to patients with deformational frontal
      plagiocephaly, in the absence of hemifacial microsomia, who frequently had
      ipsilateral torticollis but no other anomalies. This study also underscores
      possible confusion in differentiating hemifacial microsomia from deformational
      hemifacial hypoplasia on physical examination. The association of deformational
      frontal plagiocephaly and hemifacial microsomia belies a rigid etiologic label of
      deformational versus malformative anomaly.

PMID- 8291558
TI  - Genetic etiology of nuclear cataract: evidence for a major gene.
AB  - Sibling correlations and segregation analysis were used to examine the familial
      distribution of age-sex-adjusted measures of nuclear sclerosis in 1,247
      individuals from 564 sibships in the Beaver Dam Eye Study. There are highly
      significant sibling correlations for all sibs, and separately for sister-sister,
      sister-brother, and brother-brother pairs. Two transformed normal distributions
      give the best fit to the data. The hypothesis of mendelian transmission of a
      major effect cannot be rejected, but the hypothesis of a random environmental
      major effect is rejected. The parameters of the tau AB free model showed close
      similarity to the values expected under a mendelian hypothesis. Our results
      suggest that a single major gene can account for 35% of the total variability of
      age-sex-adjusted measures of nuclear sclerosis.

PMID- 8291559
TI  - Familial remitting chorea, nystagmus, and cataracts.
AB  - We report on 2 brothers with chorea and monocular horizontal nystagmus beginning
      in early infancy, both of which remit during the first decade of life, and
      peripheral cataracts. While this condition shares manifestations with benign
      hereditary chorea and several other familial movement disorders, the slowly
      remitting course of the chorea combined with the visual abnormalities appears to
      be unique.

PMID- 8291560
TI  - Model consent forms for DNA linkage analysis and storage.

PMID- 8291561
TI  - Prenatal testing in a fetus at risk for autosomal dominant polycystic kidney
      disease and autosomal recessive junctional epidermolysis bullosa with pyloric
      atresia.
AB  - Amniocentesis and fetal skin biopsies were performed at 18 weeks of gestation in
      a fetus at risk for autosomal dominant polycystic kidney disease (ADPKD) and
      autosomal recessive junctional epidermolysis bullosa (EBJ) with pyloric atresia.
      A previous son of the couple under investigation had died at 3 months of EBJ. The
      mother of the propositus has ADPKD. Genetic linkage studies were carried out in
      11 relatives (4 with ADPKD), and on fetal DNA obtained from cultured amniocytes,
      using 8 flanking DNA markers tightly linked to the PKD1 locus on chromosome 16p,
      and a DNA marker linked to another putative ADPKD locus on chromosome 2p. The
      linkage results indicated that the fetus had not inherited the ADPKD chromosome
      from the affected mother, with a diagnostic accuracy of > 99%. Ultrastructural
      and immunohistochemical analyses of multiple fetal skin biopsies showed no EBJ
      associated abnormalities. Thus, combining recent morphological and molecular
      diagnostic methods, we could show that the fetus was free from both diseases.
      After 40 weeks of gestation, a normal male infant was delivered.

PMID- 8291562
TI  - Baller-Gerold syndrome: a postmortem examination.

PMID- 8291563
TI  - On the nosology of the "Schinzel-phocomelia" and "Al-Awadi/Raas-Rothschield"
      syndromes.

PMID- 8291564
TI  - Historical note on restrictive dermopathy and report of two new cases.

PMID- 8291565
TI  - Age of onset in familial early onset Alzheimer's disease correlates with genetic
      aetiology.
AB  - Age of onset is the most robust clinical feature demarcating aetiologic subtypes
      of familial Alzheimer's disease. It has previously been noted that early onset
      disease (arbitrarily below the age of 65 years) conforms to an autosomal dominant
      pattern of transmission. Late onset disease is generally thought to have a more
      complex aetiology. We present data here suggesting that early onset disease can
      be subdivided by genetic aetiology with which age of onset correlates. In
      general, those pedigrees showing linkage to the chromosome 14 locus have a mean
      age of onset in the forties whereas those pedigrees with an APP mutation have an
      age of onset in the fifties.

PMID- 8291566
TI  - Lack of variation in the nucleotide sequence corresponding to the transmembrane
      domain of the beta-amyloid precursor protein in Alzheimer's disease.
AB  - The nucleotide sequence corresponding to the APP transmembrane domain and
      flanking regions of charged amino acids was determined for 91 patients with
      histologically confirmed Alzheimer's disease, 9 patients with dementias of other
      etiologies, and 14 controls who had no identifiable brain disease. Twenty-eight
      of the AD patients had a first-degree relative with dementia. No mutations were
      detected among the 100 demented patients. However, one of the 14 controls
      exhibited a change in the 3' base of codon 716 which would not be expected to
      result in an amino acid substitution at this position.

PMID- 8291568
TI  - Forgotten person in the Huntington disease family.
AB  - Although spouses play a major role in managing the care of persons affected with
      Huntington disease (HD), often at the price of subordinating their own
      aspirations and needs, little or no professional attention has been given to them
      in the HD literature. Such factors as secrets kept from the spouse, the early age
      of-onset of symptoms, gender, and the coping strategies employed by spouses of
      affected persons are discussed and illustrated. Also, the impact of predictive
      testing for HD on spouses of persons undergoing testing is briefly touched on.

PMID- 8291567
TI  - Presymptomatic DNA testing for Huntington disease: identifying the need for
      psychological intervention.
AB  - In the Dutch presymptomatic DNA-testing program for Huntington disease (HD), 29
      individuals with increased risk and 44 with decreased risk were followed-up 6
      months after test results. A prognostic model was built aimed at identifying
      individuals at risk for psychological maladjustment, as measured by the Impact of
      Event Scale, the Beck Hopelessness Scale, the General Health Questionnaire, and
      the Social Support Questionnaire. RESULTS: 1) The more that applicants suffered
      from intrusive feelings about HD and tried to avoid HD-related situations, prior
      to the test, the greater the chance that they will experience this 6 months after
      the test if they proved to be at increased risk; 2) the more that both
      individuals with increased risk and those with decreased risk who suffered from
      the threat of having HD tried to avoid HD-related situations prior to the test
      and the less satisfied they were with available support, the greater the
      probability that they will show avoidance behavior after the test; 3) the more
      pessimistic that individuals with increased risk as well as those with decreased
      risk were about their future prior to the test, the more they avoided HD-related
      situations and the more dissatisfied they were about their available support
      (pretest), the greater the probability that they will become depressive and
      suicidal. Psychological adjustment was also studied as a function of a)
      intrusion/denial-avoidance pattern over time and b) healthy mental
      functioning/future expectancies. Most individuals with increased risk (86%) seem
      to cope well thus far, although this was based largely on strong psychological
      defenses and dependent on satisfactory relationships.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8291569
TI  - Pseudoautosomal region in schizophrenia: sex concordance of the affected sibpairs
      and the association study with DNA markers.
AB  - To test a hypothesis that the pseudoautosomal region of the sex chromosomes
      contributes to the pathogenesis of schizophrenia, we carried out the following
      studies: First, the sex concordant rates of 77 schizophrenic sibpairs were
      examined. Secondly, 46 schizophrenic patients and 150 healthy controls were
      tested for association with DXYS17, DXYS20, DXYS28, and MIC2 in the
      pseudoautosomal region. Sex concordant rates in sibpairs with schizophrenia were
      not higher than would be expected by chance. No significant associations were
      found between four DNA markers we tested and schizophrenia. These results did not
      support the hypothesis; however, linkage disequilibrium can only be detected if
      the marker and trait loci are located close enough. Linkage analyses in multiplex
      families need to be carried out before ruling out this region as a location for a
      gene for schizophrenia.

PMID- 8291570
TI  - Co-occurrence of schizophrenia and Treacher Collins syndrome.
AB  - This is the first report of an individual with several congenital abnormalities,
      including those suggestive of Treacher Collins syndrome, and an atypical
      schizophrenic illness. Cytogenetic studies have failed to detect any recognizable
      chromosomal abnormality.

PMID- 8291571
TI  - Male siblings with schizophrenia share alleles at the androgen receptor above
      chance expectation.
AB  - In families that included two or more siblings with schizophrenia or schizo
      affective disorder male-male pairs were found to share alleles at the androgen
      receptor (AR) gene (in Xq11.2-q12) above chance expectation (p < 0.003); female
      female and mixed sex pairs showed no such tendency. The findings are compatible
      with X-Y linkage or with an X-linked contribution to liability in males.

PMID- 8291572
TI  - Failure to find linkage between schizophrenia and genetic markers on chromosome
      21.
AB  - We sought evidence for the involvement of mutations in the amyloid precursor
      protein gene (APP) in the pathogenesis of schizophrenia in two ways. First,
      linkage analysis was performed in a sample of 24 families multiply affected with
      schizophrenia. The genotypes were studied for GT12 (D21S210), a highly
      polymorphic microsatellite marker at the APP locus. Second, we used single strand
      conformation analysis (SSCA) to screen for mutations in exon 17 of APP in one
      affected member from each family and in a sample of 44 unrelated patients. In
      addition, we looked for linkage between schizophrenia and a series of highly
      polymorphic markers situated at approximately 20cM intervals along the long arm
      of chromosome 21. We were unable to find evidence for linkage to GT12 or the
      other markers studied. SSCA did not reveal any mutations in exon 17 of AP. We
      conclude that mutations within APP are an unlikely cause of schizophrenia.
      Moreover, this study provides no evidence for a major gene for schizophrenia on
      chromosome 21, and linkage can be excluded from much of this region under some
      genetic models.

PMID- 8291573
TI  - Variant cytochrome P450 CYP2D6 allelic frequencies in Parkinson's disease.
AB  - Aberrant detoxification of environmental agents may be the basis for an inherited
      predisposition to Parkinson's disease. A CYP2D6 genetic marker of the
      debrisoquine hydroxylase "poor metabolizer" phenotype was found to be
      significantly increased in Parkinson's disease patients compared to controls, as
      has been shown in previous studies. Presence of this marker gives an odds ratio
      of 1.86 for Parkinson's disease (95% confidence interval 1.33-2.39, P < 0.02).
      For comparison, a CYP1A1 polymorphism, which is not known to be associated with
      aberrant drug metabolism, showed no association with Parkinson's disease in our
      study.

PMID- 8291574
TI  - Neuropsychological impairment in 42 adolescents with sex chromosome
      abnormalities.
AB  - Sixty-seven adolescents participated in this protocol, including 42 with sex
      chromosome abnormalities and 25 controls. Results from a battery of
      neuropsychological tests indicated karyotype specific patterns of
      neuropsychological impairment: (1) 47,XXY boys had unimpaired intelligence but
      reduced abilities in verbal fluency and reading; (2) 47,XXX girls experienced
      reduced general intelligence accompanied by impaired scores on individual tests
      of attention, concept formation, spatial thinking, verbal fluency, and academic
      skills, while retention of memorized information was a relative strength; (3)
      among the 45,X girls average intelligence level was also reduced along with
      scores on tests of attention, concept formation, verbal fluency, spatial
      thinking, and academic skills, and an atypical pattern of hand dominance was
      identified; (4) test scores in the group of mosaic females did not differ from
      those of controls. Test scores and patterns of personal adaptation were quite
      variable in all groups; while eight nonmosaic propositi required intensive
      special education assistance in their public schooling, eight others have
      attended college.

PMID- 8291575
TI  - Foveomacular dystrophy.
AB  - We reviewed the clinical records of 47 patients (92 eyes) at the Wilmer Institute
      in whom foveomacular dystrophy had been diagnosed between 1977 and 1990 to
      determine reasons for initial examination, long-term visual prognosis, and the
      factors associated with visual loss. From each clinical record, we obtained the
      patient's age at the time first seen, symptoms, initial and final visual acuity,
      lesion size and appearance, and results of fluorescein angiography,
      electroretinography, and electro-oculography. The most common reasons for
      examination were decreased visual acuity in 25 of the 47 patients (53%),
      metamorphopsia in six (13%), referral for diagnosis in seven (15%), and
      misdiagnosis of age-related macular degeneration in seven (15%). Over an average
      follow-up period of 5.0 years, in 29 patients (56 eyes), visual acuity changed
      less than two lines in 41 eyes and decreased greater than or equal to two lines
      in 15 eyes. In most patients with foveomacular dystrophy, visual acuity appears
      to remain relatively stable.

PMID- 8291576
TI  - Stretch pupilloplasty for small pupil phacoemulsification.

PMID- 8291577
TI  - Wound adhesives for eyelid retraction.

PMID- 8291578
TI  - Chromosome 9 abnormality in choroidal melanoma.

PMID- 8291579
TI  - Regression of choroidal metastases from a bronchial carcinoid tumor after
      chemotherapy with cisplatin and etoposide.

PMID- 8291580
TI  - Retinal arteriovenous communications associated with features of the Sturge-Weber
      syndrome.

PMID- 8291581
TI  - Monocular blindness from central retinal artery occlusion associated with
      chickenpox.

PMID- 8291582
TI  - Panuveitis with papillitis in leptospirosis.

PMID- 8291583
TI  - Aseptic meningitis and iridocyclitis related to ibuprofen.

PMID- 8291584
TI  - Management of the posterior capsule during pediatric intraocular lens
      implantation.

PMID- 8291585
TI  - Prevalence of pigment dispersion syndrome in a population undergoing glaucoma
      screening.

PMID- 8291586
TI  - A simplified technique of orbital decompression for severe retrobulbar
      hemorrhage.

PMID- 8291587
TI  - Follow-up and ultrasonographic examination of patients with macular pseudo
      operculum.
AB  - Twenty-nine patients (30 eyes) with pseudo-opercula were followed up for six to
      65 months (mean, 24 months). Visual acuity was 20/30 or better in all but one eye
      that was amblyopic. Only one eye developed a decrease in visual acuity and
      changes interpreted as a stage 1 (foveal detachment induced by tangential
      traction of the cortical vitreous) impending hole. After vitrectomy visual acuity
      returned to 20/20. Ultrasonographic examination confirmed the presence of pseudo
      opercula in all 22 eyes examined. We concluded that the a pseudo-operculum is a
      favorable prognostic sign and that its presence is demonstrable
      ultrasonographically.

PMID- 8291588
TI  - Decreasing stromal iris pigmentation as a risk factor for age-related macular
      degeneration.
AB  - To evaluate iris color, change of iris color, and iris pigment epithelial defects
      as risk factors in age-related macular degeneration, we compared 101 patients
      with age-related macular changes with 102 control subjects in a case-control
      study. Three of 101 patients (3%) and four of 102 control subjects (4%) had
      epithelial iris defects. Light iris color during youth was reported by 51 of 101
      patients (50.5%) and 42 of 102 control subjects (41.2%) (odds ratio, 1.46; P =
      .184). Of the 101 patients, 26 (25.7%) noticed their iris color to have become
      lighter during life compared with six of 102 control subjects (5.9%) (odds ratio,
      5.5; P = .0001). At present examination, 63 of 101 patients (62.4%) had light
      irides compared with 43 of 102 control subjects (42.2%) (odds ratio, 2.27; P =
      .004). These results suggest that initial light iris color and iris pigment
      epithelial defects are not associated with an increased risk of age-related
      macular degeneration, whereas decreased stromal iris pigmentation may indicate a
      higher risk.

PMID- 8291589
TI  - Capillary blood flow velocity measurements in cystoid macular edema with the
      scanning laser ophthalmoscope.
AB  - Using a scanning laser ophthalmoscope, we calculated the velocity of retinal
      blood flow in a juxta-foveolar capillary during the course of cystoid macular
      edema after partial central retinal vein occlusion in a 53-year-old woman. The
      mean velocity of the fluorescent dots in the macular capillary of the right eye
      with cystoid macular edema was 1.59 +/- 0.08 mm/sec at the initial examination.
      Despite the systemic administration of indomethacin (75 mg/day for three weeks),
      best-corrected visual acuity decreased from 20/30 to 20/70, and the velocity
      became 0.82 +/- 0.13 mm/sec. Prednisolone (30 mg/day orally for one week)
      improved the cystoid macular edema, and the velocity was 0.96 +/- 0.06 mm/sec 12
      days after initiation of the drug. The velocity gradually improved; one year
      later it was 1.65 +/- 0.17 mm/sec and visual acuity was 20/22. Velocity in the
      left eye, which did not have cystoid macular edema, was 2.16 +/- 0.16 mm/sec.
      Thus, scanning laser ophthalmoscopy proved useful for measuring the velocity of
      retinal blood flow.

PMID- 8291590
TI  - Clinicopathologic study of ocular trauma in eyes with intraocular lenses.
AB  - Data on 41 cases (37 intraocular lenses and four globes) of intraocular lenses
      explanted or expulsed after ocular trauma were retrieved from over 5,000
      intraocular lenses and 1,200 globes. The age of the male and female donors varied
      significantly (male, 64.4 +/- 13.1 years; female, 75.5 +/- 12.6 years; P =
      .0334). Twenty-two were posterior chamber, 11 were anterior chamber, and eight
      were iris-fixated lenses. The mean implant durations were 0.66 +/- 0.9 years for
      posterior chamber intraocular lenses, 4.0 +/- 3.4 years for anterior chamber
      lenses, and 9.0 +/- 4.9 years for iris-fixated lenses. Accidental falling was the
      most common trauma in 14 of 21 cases (67%). In the posterior chamber intraocular
      lens group, trauma was more severe and resulted in rupture of the globe in 19 of
      22 cases (86%) and expulsion of the intraocular lens in 15 of 22 cases (68%).
      Rupture usually occurred at the surgical wound, even when the trauma happened
      five years postoperatively. In contrast, most of the eyes with anterior chamber
      intraocular lenses and iris-fixated intraocular lenses did not rupture, but a
      minor trauma often resulted in intraocular lens dislocation and secondary
      complications that necessitated intraocular lens explantation. The pathologic
      findings were nonspecific (proteinaceous deposits, blood and pigment adherent to
      the intraocular lens). Severity of trauma and pathologic findings were not
      correlated. Posterior chamber intraocular lenses are more resistant to minor
      ocular trauma compared to anterior chamber and iris-fixated intraocular lenses.

PMID- 8291591
TI  - Complications of hexagonal keratotomy.
AB  - We examined 15 eyes of ten patients with complications of hexagonal keratotomy,
      which included glare, photophobia, polyopia, fluctuation in vision,
      overcorrection, irregular astigmatism, corneal edema, corneal perforation,
      bacterial keratitis, cataract, and endophthalmitis. Wound healing abnormalities
      and anterior displacement of the central cornea adjacent to the incisions were
      common. Eight eyes lost best-corrected visual acuity of two or more Snellen
      lines. Three eyes required penetrating keratoplasty for visual rehabilitation.
      Histologic analysis of two of these corneas disclosed variations in wound depth
      and abnormalities of wound configuration, including considerable wound gaping.
      Hexagonal keratotomy appears to be an unpredictable, unsafe surgical procedure
      with a high complication rate, and it should be abandoned until well-controlled
      experimental trials establish its safety and efficacy.

PMID- 8291592
TI  - Comparative diagnosis of neonatal chlamydial conjunctivitis by polymerase chain
      reaction and McCoy cell culture.
AB  - Cervical and ocular swabs from 100 mother/newborn pairs delivering on the clinic
      service were assayed for Chlamydia trachomatis with standard McCoy cell culture
      and with standard and biotinylated polymerase chain reaction techniques, using
      primers directed against the major outer membrane protein gene and C. trachomatis
      specific cryptic plasmid, respectively. Using the polymerase chain reaction, 20
      (20%) mothers and seven (7%) neonates were positive for Chlamydia. All neonates
      positive by polymerase chain reaction were from mothers positive by polymerase
      chain reaction, yielding a 35% transmission rate. Only five of 20 (25%) mothers
      and two of seven (28%) neonates positive by polymerase chain reaction were
      positive by cell culture. All cell culture samples were positive by polymerase
      chain reaction testing. Culture and polymerase chain reaction analysis two weeks
      after treatment with oral erythromycin were negative. The polymerase chain
      reaction assay appears to be equally specific and more sensitive than McCoy cell
      culture for the detection of C. trachomatis from ocular specimens.

PMID- 8291593
TI  - Factors affecting visual outcome after surgery for bilateral congenital
      cataracts.
AB  - The medical records of 33 patients with dense bilateral congenital cataracts were
      analyzed for factors affecting visual outcome. The average postoperative follow
      up was 6.3 years. Of the 23 patients tested with optotypes (verbal children), 14
      had visual acuities of 20/80 or better. Eight patients had binocular vision.
      Preoperative nystagmus, age at surgery, microphthalmos, and postoperative
      strabismus were not prognostically significant in visual outcome. Postoperative
      nystagmus was common and was not indicative of a poor visual outcome. Ocular
      anomalies, systemic anomalies, and postoperative complications were associated
      with a lower percentage of good postoperative visual acuities.

PMID- 8291594
TI  - Microbial keratitis in children.
AB  - In a five-year review, we identified 29 cases of microbial infection in 28
      patients who were 16 years old or younger. Herpes simplex infections were
      excluded. Predisposing factors included trauma (ten cases, 34%), severe systemic
      illness (eight cases, 27%), contact lens use (seven cases, 24%), exposure
      keratopathy (seven cases, 24%), and previous ocular surgery (six cases, 21%). A
      total of 24 microorganisms were identified in cultures of corneal scrapings from
      22 of the 29 cases; two cases involved polymicrobial infections. Of the 24
      identified pathogens, gram-positive cocci were the most common (12). Other
      microorganisms included gram-negative bacteria (five) and fungi (four). Isolated
      cases of Acanthamoeba species, Borrelia burgdorferi, and Bacillus species were
      also present. Therapy with intensive topical antibiotics was successful in this
      series. The rate of surgical intervention (6/29, 21%) was similar to that of
      previous reports.

PMID- 8291595
TI  - Indocyanine green angiography in multiple evanescent white-dot syndrome.
AB  - Using indocyanine green angiography we examined two patients with multiple
      evanescent white-dot syndrome. Both patients had unilateral loss of vision and a
      fundus appearance typical of multiple evanescent white-dot syndrome. Fluorescein
      angiography in both patients disclosed a patchy hyperfluorescent pattern at the
      level of the retinal pigment epithelium. Using indocyanine green angiography, we
      observed multiple deep, small, round hypofluorescent lesions that appeared early
      and persisted into the late phases. The spots appeared to block the underlying
      choroidal pattern. These hypofluorescent spots were clearly visible and present
      throughout the posterior pole. Many more spots were seen on indocyanine green
      angiography than were visible by clinical examination or angiography. After
      follow-up examinations, there was a rapid resolution of the spots over four to
      six weeks with return of vision. Our findings show that indocyanine green
      angiography can be a valuable tool in the recognition and further understanding
      of multiple evanescent white-dot syndrome.

PMID- 8291596
TI  - Peripapillary vasoconstriction in the glaucomas and the anterior ischemic optic
      neuropathies.
AB  - Proximal constriction (retinal arteries narrower near the disk than further down
      the stream in the retina) was present in 96 of 226 eyes (42%) with classic
      glaucoma or normal-tension glaucoma, but it was present in only 11 of 206 eyes
      (5%) that were normal, had ocular hypertension, or had retinal disease not
      affecting the optic nerve. In cases of glaucoma with proximal constriction over
      only part of the disk circumference, its location corresponded to the sector with
      the greatest cupping in 60 of 66 cases (91%) and likewise corresponded to the
      sector in which the peripapillary zone of absent retinal pigment epithelium was
      widest in 48 of 55 cases (87%). Proximal constriction was also present in 16 of
      45 eyes (36%) with nonischemic types of non-glaucomatous optic atrophy. The
      nonarteritic form of anterior ischemic optic neuropathy had proximal constriction
      in 19 of 28 eyes (68%), which was more frequent than in those with glaucoma (P =
      .017). Only one of nine eyes with the arteritic form of anterior ischemic optic
      neuropathy had proximal constriction, which was lower prevalence than in those
      with glaucoma (P = .066). General arterial narrowing (throughout the retinal
      course) was present in 111 of 204 (54%) of those with moderate optic nerve damage
      and 100 of 128 (78%) of those with severe optic nerve damage in all categories,
      compared with 29 of 208 (14%) of the controls with no optic nerve damage. Unlike
      proximal constriction, the generalized narrowing was related to severity of optic
      nerve damage and not to the disease category.

PMID- 8291597
TI  - Visual loss caused by choroidal ischemia preceding anterior ischemic optic
      neuropathy in giant cell arteritis.
AB  - Three patients with visual loss and normal fundi were discovered to have
      choroidal ischemia on fluorescein angiography. Each patient had a markedly
      increased Westergren erythrocyte sedimentation rate, but only one described
      symptoms of polymyalgia rheumatica, neck pain, and jaw claudication. Biopsy of
      the temporal artery confirmed giant cell arteritis in the two patients without
      constitutional symptoms. In one patient, typical anterior ischemic optic
      neuropathy developed the following day, whereas in the other two, anterior
      ischemic optic neuropathy later occurred despite the prompt administration of
      intravenous high-dose corticosteroids. Choroidal ischemia may be the first sign
      of giant cell arteritis in elderly patients with visual loss. Early diagnosis and
      treatment are mandatory in an attempt to forestall the development of anterior or
      posterior ischemic optic neuropathy, or central retinal artery occlusion in the
      affected or fellow eye.

PMID- 8291598
TI  - Aqueous humor penetration of ofloxacin given by various routes.
AB  - We studied the aqueous humor penetration of ofloxacin after topical, oral, and
      intravenous administration in 51 consecutive patients undergoing cataract
      surgery. Aqueous humor concentration (mean +/- SD) was 0.53 +/- 0.35 mg/l when
      ofloxacin 0.3% eyedrops were instilled topically six times, one drop every three
      hours, until 90 minutes preoperatively, and 0.63 +/- 0.29 mg/l (P = .45) when two
      additional instillations were made, one drop every 30 minutes, until 30 minutes
      before aqueous humor aspiration. Aqueous humor concentration two hours after a
      single 200-mg oral dose (0.38 +/- 0.15 mg/l) was significantly lower (P = .048)
      than that 12 hours after the same oral dose (0.58 +/- 0.24 mg/l). Two hours
      following an intravenous infusion of 200 mg of ofloxacin, aqueous humor
      concentration was 0.33 +/- 0.19 mg/l. Our results suggest that therapeutic levels
      above the minimum inhibitory concentration for many bacteria cultured in
      endophthalmitis can be achieved in aqueous humor after either topical or oral
      administration, which indicates that this antibiotic passes easily through the
      corneal and the blood aqueous barriers.

PMID- 8291599
TI  - Traumatic chiasmal syndrome associated with midline basilar skull fractures.
AB  - We studied two young males who had visual field defects consistent with optic
      chiasmal injury after blunt frontal head trauma. One patient also had a
      unilateral optic neuropathy. Long-term follow-up disclosed complete bi-temporal
      hemianopsias in these patients. Both patients had midline basilar skull fractures
      that traversed the midclivus through the sella turcica floor, dorsum sellae, and
      sphenoid sinus. Magnetic resonance images did not identify intrachiasmal
      hemorrhage as the cause of the visual field defect. We believe this fracture
      pattern, in conjunction with the magnetic resonance image findings, suggests
      tearing of the optic chiasm on a microscopic, if not macroscopic, scale as the
      cause of the complete bitemporal hemianopsia.

PMID- 8291600
TI  - Microscopically controlled excision of conjunctival squamous cell carcinoma.
AB  - Although surgical excision, with or without adjunctive cryotherapy, is an
      accepted method of managing conjunctival squamous cell carcinoma, histologically
      verified tumor-free surgical margins cannot be assured by excision alone. We used
      a tissue conservation method, an adaptation of the Mohs' micrographic technique
      for cutaneous tumors, to monitor the conjunctival tissue margins by histologic
      review at initial tumor excision. We treated 19 patients with squamous cell
      carcinoma of the conjunctiva by this technique. Lamellar sclerectomy was used if
      the deep tissue margin was positive for residual tumor cell after the first stage
      review. Adjunctive cryotherapy was utilized in one patient because the deep
      scleral margin remained positive after lamellar sclerectomy, and further excision
      was not possible. In all patients, the tumor-free conjunctival defect was allowed
      to heal by secondary intention. During six months to 60 months of follow-up, no
      recurrences were documented. The only complication encountered was conjunctival
      scarring with secondary restricted motility in one patient. We believe this
      method of tissue margin surveillance offers a high cure rate for the treatment of
      conjunctival squamous cell carcinoma.

PMID- 8291601
TI  - Deletion mapping of chromosome 8p in colorectal carcinoma and dysplasia arising
      in ulcerative colitis, prostatic carcinoma, and malignant fibrous histiocytomas.
AB  - Short tandem repeat polymorphism markers on the short arm of chromosome 8 were
      used to search for loss of heterozygosity (LOH) in colorectal carcinoma and
      dysplasia complicating ulcerative colitis, in prostatic carcinoma, and in
      malignant fibrous histiocytoma (MFH). Fifty percent of prostatic carcinomas
      (13/26), 44% of carcinomas or dysplasias arising in ulcerative colitis (7/16),
      and 30% (4/12) of MFH cases showed LOH for markers on 8p. Detailed mapping
      demonstrated variability in the size of the chromosomal region showing LOH;
      however, the data suggest a common 30-centimorgan region of LOH on chromosome 8p
      between the LPL locus and pter in colorectal and prostatic cancers. In addition,
      LOH was observed on 8p in both high-grade and low-grade dysplasia in ulcerative
      colitis, indicating that LOH on 8p may occur at an early stage of neoplastic
      development in this disorder. In contrast, MFH cases exhibited LOH for marker
      D8S87, which has been identified as being near the putative Werner's syndrome
      locus. These results suggest that a tumor suppressor gene, located on the distal
      portion of chromosome 8p, exists in common for prostatic and colorectal
      carcinomas, and a second tumor suppressor gene may exist linked to the Werner's
      syndrome locus.

PMID- 8291603
TI  - Human papillomavirus type 18 and intraepithelial lesions of the cervix.
AB  - The conventional perception of HPV type 18 is that it is associated principally
      with invasive cancer of the cervix. However, in precursor lesions it is
      frequently identified in lesions of lower grade morphology, in contrast to the
      typical high grade lesions associated with HPV 16. To better characterize this
      uncommon relationship of low grade morphology and high risk virus, we studied
      four low grade and two high grade intraepithelial lesions of the cervix which
      were shown to contain HPV 18 by polymerase chain reaction/restriction fragment
      length polymorphism analysis. Immunohistochemistry and in situ hybridization
      identified capsid proteins and viral DNA in an epithelial distribution
      characteristic of episomal replication and late gene expression. Sequencing of
      the E2, E6, E7, and upstream regulatory regions revealed four silent mutations
      within these precursor lesions. Two of these sequence alterations were also noted
      in three of four HPV 18 positive squamous carcinomas, suggesting a viral subtype
      which was not unique to cervical precursors. The bland morphology of many HPV 18
      related precursors contrasts with the high grade morphology of HPV 18 associated
      cancers. However, this diversity cannot be linked to functional differences in
      sequences encoding in vitro transforming potential, transcriptional regulation,
      or transactivation functions. Whether these differences in lesion phenotype
      relate to unique host variables remains to be determined.

PMID- 8291602
TI  - Uptake and distribution of hepatocyte growth factor in normal and regenerating
      adult rat liver.
AB  - We have previously shown that systemically injected hepatocyte growth factor
      (HGF) is primarily taken up by the liver. The present study shows that HGF
      injected systemically or through the portal circulation is retained primarily at
      periportal sites. The periportal retention of HGF seems to persist longer in
      regenerating liver. The percentage of the total HGF injected that was retained
      within the liver at 1 minute after injection varied with the dose. A maximal
      amount of 0.157 +/- 0.012 microgram of HGF per gram liver tissue is retained by
      normal liver. Analysis of the circulating form of HGF in the plasma showed a
      relative enrichment with time for the heterodimeric form of HGF. A portion of
      portally injected HGF, composed of both single chain and two chain
      (heterodimeric) form was excreted intact in the bile. This was found in both
      normal and regenerating liver. These studies show that the liver can sequester
      large amounts of HGF and that the sequestration occurs primarily at periportal
      sites. Our studies support the hypothesis that a nonlysosomal processing pathway
      for HGF is present in the liver.

PMID- 8291604
TI  - Expression of cellular retinol- and cellular retinoic acid-binding proteins in
      the rat cervical epithelium is regulated by endocrine stimuli during normal
      squamous metaplasia.
AB  - To determine the potential roles of retinoids in the growth and differentiation
      of the reproductive tract epithelium, we have studied the expression of the
      cellular retinol- and retinoic acid-binding proteins, CRBP I and CRABP I, in the
      reproductive tract of female rats. CRBP I and CRABP I gene expression have been
      examined in the oviduct, ovary, uterus, and particularly in the cervix, which
      normally undergoes a cyclical squamous metaplasia during the estrus cycle. CRBP I
      was expressed in all four tissues examined, whereas CRABP I was expressed
      predominantly in cervix and uterus. In the cervix, CRBP I was detected in all
      epithelial layers including the columnar epithelium but was greatly reduced in
      the superficial, cornified layers of the stratified squamous epithelium. CRABP I
      was localized to the basement membrane region of the epithelium with the
      strongest expression in the basal layer of epithelial cells. While the expression
      of CRBP I and CRABP I in the keratinizing exocervix changed during the estrus
      cycle, it remained constant in the incompletely keratinized endocervix. The
      highest levels of CRBP I were seen during anestrus and proestrus, and for CRABP I
      during proestrus. Both CRBP I and CRABP I levels fell to barely detectable levels
      during estrus and metestrus. Using estrogen repletion of ovariectomized rats, we
      found that CRABP I levels transiently increased during the early proliferative
      response to estrogen, whereas CRBP I levels gradually declined, becoming barely
      detectable by 24 to 48 hours. These results suggest that CRBP I and CRABP I play
      different roles in the cyclical squamous metaplasia normally occurring in this
      tissue and that hormonal control of CRBP I and CRABP I expression might modulate
      the retinoid responsiveness of the epithelium during this process.

PMID- 8291605
TI  - Differentiation between cutaneous form of adult T cell leukemia/lymphoma and
      cutaneous T cell lymphoma by in situ hybridization using a human T cell leukemia
      virus-1 DNA probe.
AB  - Adult T cell leukemia/lymphoma (ATLL) shares overlapping clinicopathological
      features with cutaneous T cell lymphoma (CTCL), requiring detection of monoclonal
      integration of proviral DNA of type 1 human T cell leukemia virus for its
      differential diagnosis from the latter. We applied in situ hybridization (ISH)
      and polymerase chain reaction (PCR) to paraffin sections from 63 Japanese autopsy
      cases that had been diagnosed as CTCL in earlier years when ATLL was still not
      widely known. Eleven and two cases with confirmed diagnoses of ATLL and CTCL
      served as positive and negative controls, respectively. It was found that ISH was
      positive in 7 of 63 test cases and 10 of 11 positive controls, whereas PCR was
      positive in none of the test cases and eight of the positive control cases. Two
      negative controls were negative for both ISH and PCR. We conclude that ISH is
      superior to PCR for detecting type 1 human T cell leukemia virus proviral DNA on
      paraffin sections and that the ISH method is useful for differentiating CTCL from
      the cutaneous form of ATLL.

PMID- 8291606
TI  - Effect of interleukin-4 on the synthesis of the third component of complement by
      pulmonary epithelial cells.
AB  - Complement activation in the lung is important in a variety of physiological and
      pathological conditions. The third component of complement, C3, is the pivotal
      constituent of the complement cascade. C3 is produced in the lung by several cell
      types including pulmonary epithelial cells. Because pulmonary epithelial cells
      and T lymphocytes may interact within the lung to regulate local immune
      responses, we examined the effect of a T lymphocyte-derived cytokine, interleukin
      4 (IL-4) on C3 production by A549 human pulmonary epithelial cells. Treatment of
      A549 cells with IL-4 increased C3 production in a time- and dose-dependent
      fashion. Concentrations of IL-4 > or = 0.1 ng/ml significantly increased C3
      production. Maximal increase in C3 synthesis occurred after stimulation of A549
      cells with IL-4 (10 ng/ml) for 3 days. Preincubation of IL-4 with a neutralizing
      anti-human IL-4 antibody inhibited IL-4's effect on C3 production. The relative
      abundance of C3 messenger RNA levels in A549 cells increased following IL-4
      treatment, indicating that IL-4's effects on C3 production were pretranslational.
      Intercellular communication between T lymphocytes and pulmonary epithelial cells
      via cytokines such as IL-4 may be important in the local regulation of C3 gene
      expression during the inflammatory response.

PMID- 8291607
TI  - Twisted tubulofilaments of inclusion body myositis muscle resemble paired helical
      filaments of Alzheimer brain and contain hyperphosphorylated tau.
AB  - We immunostained muscle biopsies of 8 patients with sporadic inclusion body
      myositis (S-IBM), 7 patients with autosomal recessive hereditary inclusion body
      myopathy (H-IBM) (both diseases being characterized by similar muscle fiber
      vacuoles containing inclusions), and 11 normal and disease controls. We used the
      following well-characterized antibodies against tau protein: Tau-1, Alz-50, and
      anti-paired helical filament (PHF) antiserum. By light microscopy, in all S-IBM
      muscle biopsies virtually all vacuoles immunoreactive for ubiquitin and beta
      amyloid protein also contained inclusions immunoreactive with Alz-50 and anti-PHF
      antiserum. With tau-1 antibody, strong immunoreactivity in the vacuoles was
      obtained only after dephosphorylation of muscle sections. By electronmicroscopy,
      all three antibodies immunodecorated exclusively cytoplasmic twisted
      tubulofilaments (TTFs). In H-IBM, virtually all ubiquitin and beta-amyloid
      positive muscle fiber vacuoles contained inclusions immunoreactive with anti-PHF
      antiserum, but in only 40% of those fibers were the inclusions immunoreactive
      with Alz-50. In six H-IBM patients there were no tau-1 immunoreactive inclusions
      in any of their vacuolated muscle fibers; in one patient, 24% of the vacuolated
      fibers had tau-1 immunoreactivity. By demonstrating that hyperphosphorylated tau,
      which is characteristic of Alzheimer brain PHFs, is a component of S-IBM-muscle
      TTFs (which are also ultrastructurally similar to PHFs), our study: 1) provides
      the first demonstration of abnormally accumulated tau in nonneural tissue and 2)
      suggests that the cytopathogenesis in Alzheimer brain and S-IBM muscle may share
      some similar mechanisms. Whether the difference in tau immunoreactivity between S
      IBM and most of the H-IBM patients reflects a difference in genetically
      determined transcriptional or posttranslational modifications of tau protein or
      other factors remains to be determined.

PMID- 8291608
TI  - Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat).
AB  - The results of several experimental studies of focal ischemia and anecdotal
      observations suggest that leukocytes may contribute to the injury initiated by an
      arterial occlusion. The timing and the nature of leukocyte responses in evolving
      brain infarcts (either human or experimental) are incompletely characterized.
      This is a study of experimental brain lesions in 96 Wistar rats that underwent
      occlusion of a large intracranial artery for variable intervals ranging between
      30 minutes and 7 days. The experimental model, based on the occlusion of a middle
      cerebral artery ostium via the insertion of a nylon monofilament through the
      external carotid artery, does not require opening the skull; therefore, the
      inflammatory response is not influenced by the effects of craniotomy and changes
      in intracranial pressure are only those induced by the ischemic lesion. All 96
      animals having the same type of arterial occlusion developed an ischemic brain
      lesion (limited to the territory of the corresponding artery) that evolved into
      an area of extensive neuronal necrosis over a period of 6 to 12 hours followed by
      pan-necrosis (infarct) approximately 60 hours later. In this study, leukocytes
      (in particular polymorphonuclear cells) were detected in the microvessels
      (capillaries and venules) of the ischemic hemisphere as early as 30 minutes after
      the arterial occlusion. Numbers of intravascular neutrophils peaked at 12 hours,
      whereas intraparenchymal granulocytes were most numerous at 24 hours; a few
      granulocytes were visible in the brain infarct as late as day 7. Circulating
      monocytes were first detected within the capillaries/venules of the ischemic area
      after 4 to 6 hours. Platelet aggregates were more abundant in the arterial than
      the venous side of the circulation, and luminal obstruction of arteries by
      platelet aggregates became noticeable only 48 hours after the arterial occlusion.
      Fibrin thrombi were conspicuous for their absence. These observations provide the
      background for studies that will attempt to unravel the relationship between the
      biological responses of leukocytes and neuronal necrosis secondary to focal
      ischemia.

PMID- 8291609
TI  - The LEC rat: a model for human hepatitis, liver cancer, and much more.
AB  - The LEC rat is an inbred mutant strain with spontaneous hepatitis isolated from
      Long-Evans rats. Since approximately 40% of LEC rats die of fulminant hepatitis,
      the rat serves an animal model for studying the pathogenesis and treatment of
      human fulminant hepatitis. The remaining 60% of LEC rats survive and develop
      chronic (prolonged) hepatitis and subsequently develop liver cancer. Therefore,
      the LEC rat serves an important animal model for studying the significance of
      chronic hepatitis in the development of human liver cancer, which often develops
      in association with chronic hepatitis. The LEC rat can also be used as an animal
      model of Wilson's disease, since recent studies have disclosed high copper
      accumulation in the liver and low ceruloplasmin concentration in the serum of
      this mutant rat.

PMID- 8291610
TI  - Expression of p53 oncoprotein in different histological types of breast
      carcinoma.

PMID- 8291611
TI  - Acute cytomegalovirus infection induces a subendothelial inflammation
      (endothelialitis) in the allograft vascular wall. A possible linkage with
      enhanced allograft arteriosclerosis.
AB  - Clinical and experimental studies have established the accelerating role of
      cytomegalovirus (CMV) infection on cardiac allograft arteriosclerosis, ie,
      chronic rejection. We have investigated the mechanisms behind the interaction
      between CMV infection and chronic rejection. In the first part of the study, 762
      endomyocardial biopsy specimens obtained from 47 heart allograft recipients were
      analyzed. Of these, 28 patients developed CMV infection during the first
      postoperative year. In 24 of 28 CMV patients, mononuclear inflammatory cells
      (endothelialitis) were seen in the subendothelium of small intramyocardial
      arterioles. In CMV-free recipients, only five of 19 had any subendothelial
      inflammation in the vascular structures P < 0.0001 when compared with CMV
      patients). The subendothelial inflammation demonstrated an intensive peak at the
      onset of CMV infection, subsiding slowly thereafter. Morphologically, the
      inflammatory cells in the subendothelium were small lymphocytes. Only few
      activated pyroninophilic lymphocytes were seen. Immunohistochemistry revealed
      that the lymphocytes were mostly T cells (UCHL1+). In the second part of the
      study, we investigated if a similar endothelialitis could be induced
      experimentally in allografted rats. We performed rat aortic allografts from the
      DA (AG-B4, RT1a) donors to the WF (AG-B2, RT1v) recipients and infected the
      recipients with 10(5) plaque-forming units of rat CMV Maastricht strain 1 day
      after transplantation. In rat CMV-infected aortic allografts, the frequency of
      subendothelial leukocyte common antigen (LCA, OX1) positive leukocytes, 1.7 +/-
      0.1 (SEM) point score units, was significantly higher when compared to
      noninfected allografts, 0.8 +/- 0.1 point score units (P < 0.05), and they were
      most prominent in the intimal space during and following acute infection. During
      subsequent weeks, the LCA-positive leukocytes were replaced by alpha-actin
      positive smooth muscle cells. Instead, most of the cells in intima of CMV-free
      grafted rats stained positively to alpha-actin from the beginning and were smooth
      muscle cells. Practically no leukocytes were seen. In rat CMV-infected aortic
      allografts most subendothelial inflammatory cells represented T cells (W3/25+)
      and cells of the monocyte/macrophage lineage (OX42+). In conclusion, acute CMV
      infection is associated with an subendothelial inflammation (endothelialitis) of
      allograft vascular structures both in human and in rat. Nonactivated T
      lymphocytes and monocytes predominate the inflammatory lesion in the
      subendothelium. The results suggest that the virus-linked vascular wall
      inflammation may play a role in the immune injury toward allograft vascular
      structures, particularly to endothelium, and thus contribute to allograft
      arteriosclerosis.

PMID- 8291612
TI  - Disparate temporal expression of the prothrombin and thrombin receptor genes
      during mouse development.
AB  - The protease thrombin is a potent agonist for platelet aggregation, mesenchymal
      cell proliferation, and endothelial production of growth factors and adhesion
      molecules. Thrombin also modulates neurite outgrowth in neuronal cultures. These
      apparently disparate responses to thrombin appear to be largely mediated by the
      recently cloned thrombin receptor. In the adult, thrombin is generated from its
      zymogen prothrombin at sites of vascular injury when circulating coagulation
      factors meet extravascular tissue factor. In this context thrombin's varied
      actions may mediate responses to wounding. Whether thrombin's actions on cells
      may also play a role in development is unknown. We examined the expression of
      thrombin receptor, prothrombin, and tissue factor by in situ hybridization in
      mouse development. Thrombin receptor mRNA was expressed widely in mesenchymal
      cell populations during early organogenesis (E9.5) and was particularly abundant
      in developing heart and blood vessels. Robust receptor expression was also noted
      in the germinal epithelium of the hindbrain. Thrombin receptor expression became
      more restricted with time and by the fetal growth stage (E16.5) was most readily
      detected in certain neurons, endocardial and endothelial cells, and within lung
      and liver. In contrast to the thrombin receptor, prothrombin mRNA was limited to
      the embryonic liver and was not detected until E12.5, well after the onset of
      receptor expression. mRNA for tissue factor, one important trigger for thrombin
      generation in the adult, was detected in embryonic epithelia from E9.5-12.5. In
      several instances, tissue factor-expressing epithelia were surrounded by thrombin
      receptor-expressing mesenchyme. These data suggest a possible role for the
      thrombin receptor in development. The finding of robust thrombin receptor
      expression before prothrombin mRNA was detected raises the question of whether
      other proteases or peptide ligands can activate the thrombin receptor.

PMID- 8291613
TI  - Plasminogen activators, their inhibitors, and urokinase receptor emerge in late
      stages of melanocytic tumor progression.
AB  - Degradation of the extracellular matrix and other tissue barriers by proteases
      like plasminogen activators (PAs) is a prerequisite for neoplastic growth and
      metastasis. Recently, we reported that highly metastatic behavior of human
      melanoma cells in nude mice correlates with urokinase-type PA (u-PA) expression
      and activity and with PA inhibitor type 1 and 2 (PAI-1, PAI-2) expression. Here
      we report on the occurrence of components of the PA system in the various stages
      of human melanoma tumor progression in situ. We studied the protein distribution
      on freshly frozen lesions of common nevocellular nevi (n = 25), dysplastic (=
      atypical) nevi (n = 16), early primary melanomas (n = 8), advanced primary
      melanomas (n = 11), and melanoma metastases (n = 17). Tissue-type PA was present
      in endothelial cells in all lesions, whereas in metastases it could be detected
      in tumor cells in a minority of the lesions. u-PA, its receptor, PAI-1, and PAI-2
      could not be detected in benign and in early stages but appeared frequently in
      advanced primary melanoma and melanoma metastasis lesions. u-PA was detected in
      stromal cells and in tumor cells at the invasive front, the u-PA receptor and PAI
      2 in tumor cells, and PAI-1 in the extracellular matrix surrounding tumor cells.
      Localization of the corresponding messenger RNAs and enzyme activities revealed a
      similar distribution. We conclude that plasminogen activation is a late event in
      melanoma tumor progression.

PMID- 8291615
TI  - A monoclonal antibody directed against a human cell membrane antigen prevents
      cell substrate adhesion and tumor invasion.
AB  - It was the aim of this study to design mouse monoclonal antibodies (MAbs) that
      can inhibit the invasion of breast cancer cells in the host tissue. Therefore,
      MAbs were raised against epitopes on the extracellular domain of SK-BR-3 human
      breast cancer cells, and biological assays were performed to test the capability
      of the MAbs to inhibit cell substrate adhesion. MAb 14C5 bound an extracellular
      plasma membrane antigen of SK-BR-3 and MCF-7 human breast cancer cells and
      inhibited the cell substrate adhesion of these cells in vitro. The MAb delayed
      the adhesion of MCF-7 and SK-BR-3 cells on precultured embryonic heart fragments
      (PHFS). It inhibited the destruction of the PHF by MCF-7 cells and the invasion
      of the PHF by SK-BR-3 cells. The MAb reacted with an epitope on the cell membrane
      of in situ and invasive ductal carcinomas of the breast in immunohistochemistry.
      Poorly differentiated, highly invasive ductal carcinomas show extensive staining
      of long plasma membrane extensions. Normal multilayered epithelia, normal
      connective tissue, and tumors derived from these tissues as well as normal breast
      tissue were negative. From both cell lines a protein complex consisting of two
      subunits with molecular weight of 50 and 90 kd, respectively, was
      immunoprecipitated. It is concluded that the 14C5 antigen plays a role in cell
      substrate adhesion and subsequently also in invasion of breast cancer cells. The
      14C5 MAb was able to inhibit cell substrate adhesion and invasion in vitro of
      breast cancer cells.

PMID- 8291614
TI  - Transforming growth factor-beta 1 stimulates glomerular mesangial cell synthesis
      of the 72-kd type IV collagenase.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) is generally considered to exert
      positive effects on the accumulation of extracellular matrices. These occur as
      the net result of enhanced matrix protein synthesis, diminished matrix
      metalloproteinase (MMP) synthesis, and augmented production of specific
      inhibitors, including the tissue inhibitor of metalloproteinases (TIMP-1). Given
      that glomerular TGF-beta 1 synthesis is induced by inflammation, the effects of
      this cytokine on synthesis of the 72-kd type IV collagenase and TIMP-1 by
      cultured human mesangial cells were evaluated. Concentrations of TGF-beta 1 of 5
      ng/ml and above specifically stimulated the synthesis of the 72-kd type IV
      collagenase. This effect was independent of the stimulatory effect of TGF-beta 1
      on TIMP-1 synthesis, which was maximal in a lower concentration range (0.1 to 1
      ng/ml). Most significantly, the net effect at the higher concentrations of TGF
      beta 1 was an excess of enzyme over the TIMP-1 inhibitor. Northern blot analysis
      of TGF-beta 1-stimulated human mesangial cells demonstrated a specific increase
      in the abundance of the 3.1 kb mRNA transcript encoding the 72-kd type IV
      collagenase, presumably mediated by a direct stimulation of 72-kd type IV
      collagenase mRNA transcription observed as early as 3 hours after exposure to TGF
      beta 1. These studies were extended to an analysis of the expression of TGF-beta
      1 and 72-kd type IV collagenase mRNAs in normal and nephritic rats. In normal
      animals, basal TGF-beta 1 and 72-kd type IV collagenase mRNA expression was
      observed in a strictly mesangial distribution. After induction of acute immune
      complex-mediated glomerulonephritis, there was a major increase in TGF-beta 1 and
      72-kd type IV collagenase mRNA expression, which was strictly limited to the
      expanded, hypercellular mesangial compartment. Enhanced synthesis of the
      mesangial type IV collagenase in response to TGF-beta 1 released during
      glomerular inflammatory processes could have an important role in the extensive
      glomerular matrix remodeling that accompanies these disorders.

PMID- 8291616
TI  - Diffuse idiopathic skeletal hyperostosis in Meroitic Nubians from Semna South,
      Sudan.
AB  - The paleopathological study of human osteological remains from the site of Semna
      South, of northern Sudan, revealed that about thirteen percent of this ancient
      Nubian population had diffuse idiopathic skeletal hyperostosis (DISH). As in
      modern cases, males were more affected than females. Two thousand years ago,
      ancient Nubian males had the same spinal problems elderly men have today.

PMID- 8291617
TI  - Treponematosis in regional and chronological perspective from central Gulf Coast
      Florida.
AB  - Examination of five central Gulf Coast Florida archaeological skeletal series (n
      = 547) from the late prehistoric and early historic periods reveals the presence
      of pathological lesions characteristic of treponemal infection. These skeletal
      remains of native American populations represent a crucial time regarding
      hypotheses about the exchange of syphilis between the Old and New World or the
      mutation of one treponemal infection into another. Comparison of the lesions with
      those observed in modern studies of treponemal infection does not support an
      interpretation of venereal syphilis. The data from this study and from other
      archaeological skeletal series indicate the presence of a treponemal disease
      prior to European contact. The skeletal elements from Florida do not suggest that
      the disease changed dramatically following contact with Europeans. It is possible
      that cases of nonspecific postcranial pathology can be explained by the presence
      of this disease in the Florida populations. This study indicates that a
      treponemal disease was endemic throughout the region by at least A.D. 1000.

PMID- 8291618
TI  - Paleoserology of the Christian population at Sayala (Lower Nubia): an evaluation
      of the reliability of the results.
AB  - A paleoserological study of human remains from the Christian cemeteries of Sayala
      (Lower Nubia, 6th-11th centuries A.D.) was carried out by applying two techniques
      (absorption-elution and haemagglutination-inhibition), on two types of substratum
      (bones and hair), in separate laboratories (Pisa and Prague). The aim of research
      was to evaluate the degree of repeatability of the results and the reliability of
      the final paleoserological diagnoses. The results indicated different degrees of
      repeatability depending on the differential sensitivity of the two techniques and
      on the nature of the substratum. The frequencies of concordant and discordant
      final diagnoses within and between the two laboratories and by the two methods
      were significantly different from those expected under the conditions of random
      distribution, indicating a consistency in results from different laboratories and
      methods. The reliability of the resulting gene and phenotype distributions is
      also supported by their consistency both with the theoretical Hardy-Weinberg
      equilibrium and with the present distribution of the ABO gene frequencies in
      Egyptian, Sudanese, and Nubian populations.

PMID- 8291619
TI  - Growth of nomadic and settled Turkana infants of northwest Kenya.
AB  - Turkana tribespeople reside in a semi-arid savanna ecosystem in northwest Kenya.
      For over a decade, Ngisonyoka Turkana nomads have been studied within a
      multidisciplinary framework that embraces ecology, anthropology, and human
      population biology. Original research objectives of the South Turkana Ecosystem
      Project were to study nomads longitudinally and within the context of the dry
      savanna ecosystem. These objectives have been expanded to incorporate settled
      Turkana who were nomads in the recent past, but who, for a variety of reasons,
      have taken up a life of sedentary cultivation. The research described here
      focused on comparisons of growth patterns of nomadic and settled infants from
      birth to 24 months of age. Infants were measured (recumbent length, weight, head
      circumference, arm and calf circumference, and selected skinfolds) in 1989 and
      1990. Settled infants were slightly longer, but nomadic infants were heavier and
      fatter. Head circumferences were the same. Some variation was observed by season
      and year of measurement (from comparative surveys). Both groups showed pronounced
      weight faltering after 6 months of age when compared with U.S. NCHS reference
      values. Head circumference faltering was moderate and recumbent length faltering
      was only slight after 12 months of age. Comparisons of Turkana infant growth in
      the two populations can contribute indirectly to a better understanding of infant
      nutritional status, probable morbidity, and other factors, some of which may be
      linked to female reproduction.

PMID- 8291620
TI  - Torso morphology and locomotion in Proconsul nyanzae.
AB  - A new partial skeleton of Proconsul nyanzae from Mfangano Island, Kenya (KNM-MW
      13142) includes five lumbar vertebrae, a partial sacrum, and nearly complete
      hipbone. Until recently, little was known of the axial and pelvic skeletons of
      Proconsul, or any early Miocene hominoid. Because torso morphology directly
      reflects locomotor behavior, these elements provide important new information
      about posture and locomotion of P. nyanzae. Two basic patterns of locomotor
      behavior and corresponding torso morphology exist among extant anthropoids.
      Monkeys have long, flexible spines with powerful epaxial muscles and
      mediolaterally narrow thoraces. This morphology represents a response to the
      mechanical requirements of habitual pronograde quadrupedalism. In contrast,
      hominoids, particularly great apes, have shorter, stiffer spines and broader
      torsos than do monkeys. The hominoid pattern reflects an emphasis on forelimb
      abduction-adduction, and on stability and control of the lower back during
      forelimb-dominated arboreal locomotion. KNM-MW 13142 had craniocaudally elongate
      vertebral bodies, and probably six lumbar vertebrae, reflecting a long, flexible
      vertebral column. The narrow, laterally facing iliac blades of KNM-MW 13142 imply
      the presence of a mediolaterally narrow, dorsoventrally deep thorax. Its wide
      iliac tuberosities, ventrally located lumbar transverse processes, and distinct
      accessory processes suggest that Proconsul nyanzae also had strap-like epaxial
      muscles similar to those characterizing most monkeys. Axial and pelvic morphology
      of KNM-MW 13142 indicate that P. nyanzae had not undergone an ape-like
      rearrangement of its torso to adapt to forelimb-dominated arboreality. Instead,
      P. nyanzae probably retained a more primitive pattern of pronograde
      quadrupedalism. This morphology indicates that the extant hominoid pattern of
      torso anatomy arose subsequent to the establishment of the hominid clade.

PMID- 8291621
TI  - Facial anatomy of Victoriapithecus and its relevance to the ancestral cranial
      morphology of Old World monkeys and apes.
AB  - Recently discovered craniofacial fossils of the middle Miocene cercopithecoid
      Victoriapithecus are described. The frontal, zygomatic, maxilla, and premaxilla
      anatomy differ from the previously proposed colobine-like ancestral
      cercopithecoid morphotype in several significant respects. This morphotype was
      based on the assumption that features held in common by subordinate hominoid and
      cercopithecoid morphotypes (Colobinae and Hylobatidae) are primitive for Old
      World monkeys. Cranial similarities between Victoriapithecus, which represents
      the sister-group of both colobine and cercopithecine monkeys, and the shorter
      snouted Cercopithecinae (Macaca and Cercopithecus) indicate that the last common
      ancestor of Old World monkeys possessed the following features: a narrow
      interorbital septum, moderately long snout, moderately long and anteriorly
      tapering premaxilla, large procumbent upper central incisors set anterior to and
      with longer roots than lateral incisors, moderately tall face below the orbits,
      teardrop-shaped nasal aperture of low height and moderate width, and probably
      long and narrow nasal bones. The Victoriapithecus cranium is also characterized
      by features not present in modern cercopithecids. These include a deep malar
      region of the zygomatic and the presence of a frontal trigon due to the
      occurrence of temporal lines that merge with supraorbital costae close to the
      midline of each orbit and converge anterior to bregma. These features are
      interpreted as primitive retentions from the basal catarrhine condition as
      indicated by the occurrence of these features among primitive catarrhines
      (Aegyptopithecus) and Miocene hominoids (Afropithecus).

PMID- 8291622
TI  - Cranial growth and growth dimorphism in Ateles geoffroyi.
AB  - With the exception of the work of Schultz (1960), cranial growth in Ateles is not
      well documented. This paper describes the results of a detailed quantitative
      study of cranial ontogeny in male and female Ateles geoffroyi. Using Euclidean
      Distance Matrix Analysis (EDMA), local areas of form change due to growth within
      spider monkey crania are identified. We found substantial change local to the
      zygomatic region in the face, identified mediolaterally directed changes in the
      palate, detected relatively larger amounts of change local to the anterior
      neurocranium compared to the posterior neurocranium, and demonstrate a greater
      amount of basicranial growth along a mediolateral axis than previously reported.
      Cranial sexual dimorphism is also examined. A. geoffroyi is noted for being
      monomorphic, and we found a general similarity between male and female cranial
      forms at all developmental ages. However, differences in overall cranial size
      between the sexes were found in the oldest subadult age group but not between
      male and female adults. This difference suggests that A. geoffroyi females attain
      their adult cranial form slightly before males and implies a pattern of earlier
      onset of female maturity relative to males.

PMID- 8291623
TI  - Brief communication: an update on stature estimation in prehistoric Native
      Americans of Ohio.
AB  - We present regression equations to estimate skeletal height and stature for
      prehistoric Native Americans of Ohio. The regression equations are based on
      skeletal height as the dependent variable and various postcranial elements and
      combinations of elements as the independent variables. A total of 171
      individuals, 95 males and 76 females, make up the sample. The present sample
      includes the 64 individuals we previously used for stature estimation (Sciulli et
      al.: Am. J. Phys. Anthropol. 83:275-280, 1990) and 107 additional individuals
      distributed more widely in time and space. The present more inclusive sample,
      however, shows the same proportional contributions to skeletal height of each
      skeletal height component as the previous sample. This result suggests that these
      proportions were a consistent feature of the prehistoric Native Americans of
      Ohio. Because the prehistoric Native Americans of Ohio were characterized by
      relatively long legs and distal elements of the limbs, stature estimation from
      regressions based on East Asian populations, which express in general relatively
      short legs and distal limb elements, will overestimate stature in Native
      Americans of Ohio and, possibly, all Eastern Woodlands Native Americans.

PMID- 8291624
TI  - Presidential address of the American Orthopaedic Society for Sports Medicine.
      From adolescence to adulthood: prepared for leadership in sports medicine in the
      21st century.

PMID- 8291625
TI  - The accuracy of the clinical knee examination documented by arthroscopy. A
      prospective study.
AB  - The diagnostic accuracy of the clinical examination for intraarticular injuries
      of the knee was documented by arthroscopy over a 6-month period. Two-hundred
      ninety patients (296 knees) were evaluated by history, physical examination, and
      standard radiographs. Supplemental diagnostic studies included 41 magnetic
      resonance images, 2 arthrograms, and 1 previous arthroscopy that had been
      recently performed. Overall, the correct diagnosis was made in 165 knees (56%),
      an incomplete diagnosis in 92 (31%), and an incorrect diagnosis in 39 (13%).
      There were only 2 knees (0.07%) with no discernable lesions. When a single lesion
      was present in the knee, the diagnosis was made correctly in 72% of cases. When
      more than 2 were discovered, the diagnosis was correct in only 30%. However, all
      individual lesions were diagnosed with an accuracy of greater than 90%. The
      lesions most difficult to diagnose were chondral fractures, fibrotic fat pads,
      tears in the anterior cruciate ligament, and loose bodies. Knees with acute
      lesions and those with a single diagnosis proved to be significantly easier to
      diagnose (P < 0.01). The variables that proved to be insignificant were age, sex,
      magnetic resonance imaging, surgeon, workers' compensation, or pending
      litigation.

PMID- 8291626
TI  - Locked bucket-handle meniscal tears in knees with chronic anterior cruciate
      ligament deficiency.
AB  - Because we noticed patients had difficulty regaining full range of motion after
      surgery for a locked bucket-handle meniscal tear with simultaneous reconstruction
      for a chronic anterior cruciate ligament tear, we adopted a two-stage procedure
      for this group of patients. We evaluated the results of a two-stage procedure in
      the knees of 16 athletes (Group 1) and compared their outcome with the outcome of
      16 matched athletes who had been treated with simultaneous repair or removal of
      the displaced bucket-handle meniscal tear and autogenous patellar tendon anterior
      cruciate ligament reconstruction (Group 2). Four patients in Group 2 required a
      second procedure or casting to regain full extension. No patient in Group 1
      required a second procedure. One meniscal retear was detected in Group 1. The two
      stage procedure also appears to have a number of theoretical advantages: 1) more
      aggressive use of repair rather than removal of a displaced torn meniscus, 2)
      prevention of problems in regaining range of motion, 3) allows a second look to
      judge the success of meniscal repair, and 4) allows time for the patient to
      prepare for anterior cruciate ligament reconstruction physically, mentally,
      academically, and socially.

PMID- 8291627
TI  - Arthroscopic suture repair of superior labral detachment lesions of the shoulder.
AB  - Twenty consecutive patients with superior labral anterior and posterior lesions
      of the shoulder involving the biceps attachment to the labrum (Snyder types II
      and IV) were repaired arthroscopically and reviewed post-operatively to evaluate
      the efficacy of the technique in the management of this recently described injury
      pattern. Follow-up time averaged 21 months (range, 12 to 42). All patients were
      managed by an arthroscopic repair technique that included debridement of the
      frayed labrum and abrasion of the superior glenoid neck, followed by the
      placement of multiple sutures into the torn labrum-biceps tendon complex using a
      Caspari suture punch. Patients were reexamined, and the results were quantitated
      with the shoulder evaluation form of the American Shoulder and Elbow Surgeons and
      with the Rowe rating scale. On evaluation, all patients obtained good or
      excellent results. This suture technique is recommended in the management of
      unstable superior labral detachment lesions of the shoulder.

PMID- 8291628
TI  - Operative versus nonoperative treatment of Achilles tendon rupture. A prospective
      randomized study and review of the literature.
AB  - One hundred eleven patients with acute rupture of the Achilles tendon were
      included in a prospective trial and randomly assigned to groups for operative (56
      patients) or nonoperative (55 patients) treatment. All of the patients were
      followed with clinic evaluations at 4 months and 1 year after the rupture. The
      major complications in the operative treatment group were three reruptures and
      two deep infections as compared with seven reruptures, one second rerupture, and
      one extreme residual lengthening of the tendon in the nonoperative group. There
      were fewer minor complications in the nonoperative group than in the operative
      group. The operatively treated patients had a significantly higher rate of
      resuming sports activities at the same level, a lesser degree of calf atrophy,
      better ankle movement, and fewer complaints 1 year after the accident. The
      conclusion we reached through this randomized prospective study is that operative
      treatment of ruptured Achilles tendons is preferable, but nonoperative treatment
      is an acceptable alternative.

PMID- 8291629
TI  - Skier's thumb--the significance of bony injuries.
AB  - In a retrospective study to determine the anatomic nature of injuries in thumbs
      that were treated surgically for either fracture or instability, we reviewed 63
      consecutive patients with acute skier's thumb injury. Of the 63 thumbs, 25 (40%)
      had a fracture. Surgical exploration showed 2 fracture types: a fragment that was
      attached to the ulnar collateral ligament, and a fragment that was not attached
      to the ulnar collateral ligament. The 1st type, corresponding to true avulsion
      fracture of the ulnar collaternal ligament, was found in 8 cases; the same
      fracture type was seen in another 7 cases, with an isolated fragment that was not
      attached to the ligament. Such an isolated fragment was observed in 10 other
      cases in which the ulnar collateral ligament was completely disrupted. This type
      of bony fragmentation cannot be differentiated from a bony avulsion of the ulnar
      collateral ligament on routine films. Therefore, stress testing the injured thumb
      is mandatory even when bony avulsion fracture with minimal displacement is
      suspected from a radiograph, as indeed the fracture may not be a bony avulsion
      but may be a fragmentation of the ulnar volar aspect of the proximal phalanx
      associated with a complete disruption of the ulnar collateral ligament.

PMID- 8291630
TI  - Muscular control of the ankle in running.
AB  - The purpose of this study was to describe and compare the muscle firing patterns
      of the muscles controlling the ankle during running. Fine-wire electrodes
      monitored the activity of the gastrocnemius, soleus, peroneus brevis, tibialis
      posterior, and tibialis anterior muscles during 3 paces of running. High-speed
      film was used to synchronize the electromyographic data with the phases of
      running. The subjects were 15 recreational and competitive runners who were
      injury-free. There were 3 significant findings. First, the firing patterns of all
      of the posterior muscles demonstrated peak activity during midstance phase. Thus,
      these muscles were contracting in an eccentric fashion to control ankle
      dorsiflexion as the center of gravity passed over the ankle. Second, the tibialis
      anterior muscle fired above the fatigue threshold for 85% of the time. This may
      account for the high number of fatigue-related injuries to the tibialis anterior
      muscle seen in runners. Third, there was a significant increase of activity in
      the peroneus brevis muscle as the pace increased. This indicates the importance
      of training this muscle when pace is increased. Using this information, a sport
      specific effective and efficient exercise program for runners can be developed.

PMID- 8291631
TI  - Surgical management of exertional compartment syndrome of the lower leg. Long
      term followup.
AB  - Forty-six limbs in 28 patients were surgically treated for exertional compartment
      syndrome. One group of 16 patients (26 limbs) underwent a fasciotomy for
      exertional anterior compartment syndrome (Group 1). A second group of 12 patients
      (20 limbs) underwent a fasciotomy for exertional deep posterior compartment
      syndrome (Group 2). Patients in Group 2 experienced symptoms for a significantly
      longer time than those in Group 1:16 versus 6.8 months (P < 0.01). All three of
      the pressure measurements used in this study (resting pressure, 1 minute after
      exercise, and 5 minutes after exercise) were significantly higher in both groups
      than in normal controls (P < 0.01). The 1 minute after exercise values were
      significantly higher in Group 1 (mean, 36.5) than in Group 2 (mean, 29.1) (P <
      0.01). In Group 1, 25 of 26 limbs (96%) had excellent results. In Group 2, 13 of
      20 limbs (65%) had satisfactory results (5 excellent and 8 good) and 7 (35%) had
      unsatisfactory results (4 fair and 3 poor). Those patients who had an
      unsatisfactory outcome did so within 6 months. Patients in Group 1 had a
      significantly higher rate of satisfactory results than those in Group 2 (P <
      0.05).

PMID- 8291632
TI  - The strength of the central third patellar tendon graft. A biomechanical study.
AB  - Thirty-seven bone-patellar tendon-bone composite grafts from the knees of 21
      human cadavers were tested to failure. Average donor age was 28 years. The
      composites were divided into 4 groups: 3 groups with 10 grafts (5 pairs) and 1
      group with 7 grafts from 6 donors. In Group 1 we tested 10- versus 15-mm wide
      grafts that were used without twisting; Group II, 10-mm wide grafts without
      twisting versus 10-mm wide grafts that were twisted 90 degrees; Group III, 10-mm
      wide grafts twisted 90 degrees versus 10-mm wide grafts twisted 180 degrees; and
      Group IV, 10- versus 7-mm wide grafts that were not twisted. The tests were
      performed using a newly described potting technique and clamp system and a
      servohydraulic testing machine with an elongation rate of 5 cm/sec. The results
      of this study suggest that the central third of the patellar tendon is stronger
      than previously reported. The mean ultimate load of a 15-mm bone-patellar tendon
      bone composite was 4389 N (+/- 708); of the 10-mm wide composites, 2977 N (+/-
      516); and of the 7-mm composites, 2238 N (+/- 316). Twisting the graft 90 degrees
      increased the strength (P < 0.05). Further twisting to 180 degrees had no
      significant effect compared with twisting 90 degrees. This study supports the
      practice of using smaller (10 mm) bone-patellar tendon-bone grafts to avoid the
      potential complications of patellar fracture and graft impingement in the notch.

PMID- 8291633
TI  - Achilles tendon allograft reconstruction of the anterior cruciate ligament
      deficient knee.
AB  - Thirty-five patients had reconstruction of the anterior cruciate ligament with
      intraarticular fresh-frozen Achilles tendon allograft and extraarticular tibial
      band tenodesis. Patients were followed 2 to 4 years (mean, 2.5). Evaluation
      included clinical and functional examinations, measurement of tibiofemoral
      displacement, and anteroposterior and lateral radiographs. Clinical results were
      considered satisfactory in 85% of the patients; 16 had arthroscopic examination
      after the allograft; allograft biopsies in 9 at this time showed cellular and
      vascular tissue without evidence of immune reaction. Clinical, arthroscopic, and
      biopsy results were favorable, but radiologic results were not. In most patients
      there was a significant size increase in femoral and tibial bone tunnels, as
      measured from radiographs. In the 6 most extreme cases, bone tunnels measured 20
      mm or more in diameter, twice the initial size. Etiology and clinical
      significance of these bone tunnel changes remain unknown. Enlargement appears to
      occur early after operation; it stabilizes within 2 years. No statistical
      correlation was seen between tunnel enlargement and results of clinical and
      functional examinations; nevertheless, unexplained tunnel enlargement is cause
      for concern, and allograft replacement of the anterior cruciate ligament with
      fresh-frozen Achilles tendon allograft should be considered a salvage procedure.

PMID- 8291634
TI  - The significance of isometer measurements and graft position during anterior
      cruciate ligament reconstruction.
AB  - Intraoperative isometry measurements are commonly performed before bone tunnel
      drilling during anterior cruciate ligament reconstruction. The relationship
      between initial isometer measurements and final graft isometry, however, is
      unclear. We tested 15 cadaveric knees to determine the relationship between
      isometer readings and final graft isometry. We found that isometer readings may
      vary widely from final graft isometry because of eccentric placement of the
      anterior cruciate ligament graft within bone tunnels. Isometer measurements may
      be used, however, to predict accurate final graft isometry for specific graft
      positions within the bone tunnels.

PMID- 8291635
TI  - Anterior subcutaneous transfer of the ulnar nerve in the athlete.
AB  - To evaluate the effectiveness of subcutaneous subfascial anterior transfer of the
      ulnar nerve in the surgical treatment of cubital tunnel syndrome in athletes, we
      retrospectively reviewed athletes undergoing subcutaneous anterior transfer of
      the ulnar nerve at the elbow. Criteria for inclusion in the study included active
      participation in athletic activity, confirmed cubital tunnel syndrome, failure to
      respond to conservative treatment, and having an anterior subcutaneous subfascial
      transfer as the only procedure performed. Twenty athletes underwent a total of 21
      procedures. Results were evaluated by time to return to sport and a questionnaire
      developed to evaluate elbow function in the athlete. The athletes returned to
      full activity at an average of 12.6 weeks. Average subjective postoperative
      scores were 84. Elbow rating scores averaged 9 (range, 0 to 10). Anterior
      subcutaneous subfascial transfer of the ulnar nerve is a safe, effective means
      for treating cubital tunnel syndrome in athletes. The findings in this study are
      significant in that they confirm the effectiveness of the subcutaneous subfascial
      transfer procedure in returning the athlete to competition. Of secondary
      importance is the development of an elbow rating questionnaire appropriate to the
      athlete.

PMID- 8291636
TI  - Vertebral ring apophysis injury in athletes. Is the etiology different in the
      thoracic and lumbar spine?
AB  - In a radiologic study of the thoracolumbar spine in 143 athletes aged 14 to 25
      years and 30 male nonathletes aged 19 to 25 years, abnormalities of the vertebral
      ring apophyses were analyzed. Abnormalities affecting the anterior part of the
      vertebral ring apophysis occurred exclusively in athletes and they were most
      common in wrestlers and female gymnasts. Different types of abnormalities were
      found and the type of abnormality was related to the spinal level. We propose
      that this is related to trauma of various types. Excavation of the anterior part
      of the vertebra, probably from compression forces, was mainly found in the
      thoracic and thoracolumbar junction of the spine. Persisting or enlarged
      apophysis, probably caused by avulsion of the anterior part of the vertebral ring
      apophysis, was only found in the lumbar spine.

PMID- 8291637
TI  - Intraarticular abnormalities in association with posterior cruciate ligament
      injuries.
AB  - The effect of an isolated injury of the posterior cruciate ligament on the
      articular cartilage and menisci has not been extensively studied. Intraarticular
      abnormalities in 88 arthroscopically proven posterior cruciate ligament tears in
      symptomatic patients with straight unidirectional posterior instability were
      reviewed. There were 33 patients with acute injuries (range, 3 to 21 days; mean,
      14) and 55 patients with chronic tears (range, 28 to 3650 days; mean, 786). Of
      the acute injuries, chondral defects occurred in 4 patients (12%) and meniscal
      tears in 9 patients (27%; 6 lateral and 3 medial). Chondral defects of both the
      lateral femoral condyles and patella were present in all 4 patients. Of the
      chronic injuries, chondral defects occurred in 27 (49%) and meniscal tears in 20
      patients (36%) (7 lateral and 17 medial). Chondral defects of the medial femoral
      condyle were most common. The mechanism of injury resulting in an isolated injury
      of the posterior cruciate ligament is most likely to affect the lateral
      compartment or the articular cartilage of the patella. The incidence of articular
      defects and the incidence of meniscal tears increased in patients with chronic
      posterior cruciate ligament injuries; both lesions increased most in the medial
      compartment.

PMID- 8291638
TI  - A role for hydrotherapy in shoulder rehabilitation.

PMID- 8291639
TI  - An epidemiologic study of sports and weight lifting as possible risk factors for
      herniated lumbar and cervical discs. The Northeast Collaborative Group on Low
      Back Pain.
AB  - The associations between participation in several specific sports, use of free
      weights, and use of weight lifting equipment and herniated lumbar or cervical
      intervertebral discs were examined in a case-control epidemiologic study.
      Specific sports considered were baseball or softball, golf, bowling, swimming,
      diving, jogging, aerobics, and racquet sports. Included in the final analysis
      were 287 patients with lumbar disc herniation and 63 patients with cervical disc
      herniation, each matched by sex, source of care, and decade of age to 1 control
      who was free of disc herniation and other conditions of the back or neck. Results
      indicated that most sports are not associated with an increased risk of
      herniation, and may be protective. Relative risk estimates for the association
      between individual sports and lumbar or cervical herniation were generally less
      than or close to 1.0. There was, however, a weak positive association between
      bowling and herniation at both the lumbar and cervical regions of the spine. Use
      of weight lifting equipment was not associated with herniated lumbar or cervical
      disc, but a possible association was indicated between use of free weights and
      risk of cervical herniation (relative risk, 1.87; 95% confidence interval, 0.74
      to 4.74).

PMID- 8291640
TI  - Echography of external iliac artery endofibrosis in cyclists.
AB  - Forty-eight cyclists were studied for suspected external iliac artery
      endofibrosis with ultrasound B-mode imaging. In highly trained competition
      cyclists, symptoms of external iliac artery endofibrosis were characterized by
      lower limb claudication during maximal effort that was caused by fibrosis
      thickening of the intima of the external iliac arterial wall. Typical ultrasound
      imaging aspects consisted of parietal thickening, enhanced echogenicity of the
      arterial wall, straightness of the abnormal arterial segment, and mild narrowing
      of the arterial diameter of the proximal or medial segment of the diseased
      external iliac artery. Although ultrasound B-mode imaging study seems to be
      useful in the diagnosis of external iliac artery endofibrosis, results with this
      technique must be compared with results of clinical examination, physiologic
      tests, and arteriography.

PMID- 8291641
TI  - Complications of arthroscopic meniscal repair.
AB  - The results of 101 consecutive arthroscopic meniscal repairs were studied to
      determine the nature and frequency of associated complications. All arthroscopic
      repairs were done by the senior author (OS) between November 1984 and June 1991.
      Our data include 65 patients with associated anterior cruciate ligament injuries,
      of which 49 underwent concurrent arthroscopic anterior cruciate ligament
      reconstruction. There was an overall complication rate of 18%. There was a 20%
      risk of complication with meniscal repair when associated with anterior cruciate
      ligament injury and 14% without anterior cruciate ligament injury. There was a
      10% incidence of arthrofibrosis when meniscal repair was performed with anterior
      cruciate ligament reconstruction and a 6% incidence when performed in an anterior
      cruciate ligament-deficient, non-reconstructed knee. Overall, there was a 13%
      risk of complication with lateral repairs compared with 19% with medial repairs.
      In the subset of patients with intact anterior cruciate ligaments and isolated
      meniscal lesions, there were no complications associated with lateral repair and
      an 18% risk of complication with medial repair. Female patients demonstrated a
      higher likelihood of complication (29%) than male patients (13%). Excluding
      repair failures, there was an 8% reoperation or rehospitalization rate.

PMID- 8291642
TI  - Meniscal repair. Description of a surgical technique.

PMID- 8291643
TI  - Pull-out strength of suture anchors for rotator cuff and Bankart lesion repairs.
AB  - Surgical reconstructions of anterior-inferior shoulder instabilities and rotator
      cuff injuries require secure fixation of soft tissue to bone. Sutures are
      inserted directly through transosseous tunnels in current techniques, which are
      surgically complex and not always adequate for fixation strength. Using fresh
      frozen cadaveric human specimens, our objectives were 1) to compare immediate
      pull-out strength of two versions of polyacetal suture anchors (wedge and rod)
      with conventional suture-only attachment techniques in Bankart lesion and rotator
      cuff repairs, and 2) to compare pull-out strength of the two polyacetal suture
      anchors with a metallic suture anchor. Our results indicate no significant
      differences in fixation strength of Bankart lesions or rotator cuff repairs using
      sutures only, or using wedge or rod polyacetal suture anchors (P = 0.70). Pull
      out force did not differ significantly (P = 0.37) between the two polyacetal
      anchors. Polyacetal anchors exhibited higher pull-out forces than metallic
      anchors when inserted into metaphyseal regions of the tibia and significantly
      higher pull-out forces (P < 0.001) when inserted into metaphyseal regions with
      thicker cortical walls. Our results indicate that both polyacetal suture anchors
      provide adequate immediate fixation for soft tissue repairs in the human
      shoulder.

PMID- 8291644
TI  - The biomechanics of interference screw fixation of patellar tendon anterior
      cruciate ligament grafts.
AB  - Twenty-seven paired human cadaveric knee specimens were used to determine the
      effect of surgical technique and various interference screw parameters on the
      pullout strength of patellar tendon femoral bone blocks. The study compared the
      fixation strength of endoscopically inserted and conventional "rear-entry" screws
      of different diameters and lengths. In all tests the most frequent mode of
      failure was bone block pullout from the interference screw. There was no
      significant difference in fixation strength between 9-mm diameter screws inserted
      through a conventional rear-entry technique and 7-mm diameter screws inserted
      through an endoscopic technique. There was no significant effect of screw length
      on fixation strength. The pullout force for 20-mm long screws increased on
      average 120% when 7-mm diameter screws were compared with 5.5-mm diameter screws.
      There was no significant effect of increased screw core diameter on fixation
      strength. There was a weak positive correlation (r2 = 0.45) between screw
      insertion torque and pullout force. Our measured mean pullout force for the 7-mm
      endoscopically inserted screws of 362 +/- 198 N represents 20.1% of the failure
      load of the normal young adult anterior cruciate ligament. Our data indicate that
      properly inserted 7-mm diameter endoscopic interference screws can provide
      fixation strengths of patellar tendon anterior cruciate ligament grafts
      equivalent to those of conventional 9-mm diameter rear-entry, outside-in screws.

PMID- 8291645
TI  - Return of normal gait patterns after anterior cruciate ligament reconstruction.
AB  - Individuals with anterior cruciate ligament deficiency typically do not have
      quadriceps activity during stance. This aberrant pattern has been termed
      "quadriceps avoidance" gait. We performed gait analysis during walking on 10
      normal controls and 10 subjects 8 to 12 months after they had anterior cruciate
      ligament reconstruction using autogenous middle third of the patellar tendon. All
      patients had good subjective and objective results at the time of analysis.
      Differences in gait between subjects and controls persisted up to 12 months after
      surgery. Specifically, subjects with anterior cruciate ligament reconstructions
      demonstrated significant reductions in midstance knee flexion moments (P < 0.01)
      and tibially directed loading rates (P < 0.05) when compared with controls.
      However, the subjects had a net external flexion moment throughout most of the
      stance phase of gait, implying that quadriceps activity was present. After
      anterior cruciate ligament reconstruction, there is a tendency toward gait
      normalization, and a quadriceps avoidance mechanism is no longer present.

PMID- 8291646
TI  - Hypothenar hammer syndrome in a young female badminton player. A case report.

PMID- 8291647
TI  - Ganglion cyst of the anterior cruciate ligament. A case report of an unusual
      cause of mechanical knee symptoms.

PMID- 8291648
TI  - Fluoroscopic demonstration of acute disruption of the fifth metatarsophalangeal
      sesamoid bones.

PMID- 8291649
TI  - "The predictive value of radiographs in the evaluation of unilateral and
      bilateral anterior cruciate ligament injuries".

PMID- 8291650
TI  - Retiform hemangioendothelioma. A distinctive form of low-grade angiosarcoma
      delineated in a series of 15 cases.
AB  - Fifteen cases of a distinctive type of low-grade angiosarcoma of the skin are
      described. Most tumors presented in the second to fourth decades of life, the
      youngest patient being 9 years old and the oldest 78 (mean age, 36 years). There
      was no sex predilection. Six tumors arose on the lower limb, four on the upper
      limb, three on the trunk, and one each on the penis and the scalp. One case arose
      in the setting of chronic lymphedema and another following radiotherapy for
      carcinoma of the uterine cervix. Distinctive morphologic features were the
      presence of long arborizing blood vessels arranged in a retiform pattern
      (reminiscent of normal rete testis) lined by monomorphic hobnail endothelial
      cells, a very prominent lymphocytic infiltrate in most cases, and the focal
      presence of papillae with hyaline collagenous cores, similar to those seen in
      malignant endovascular papillary angioendothelioma (Dabska's tumor). With a
      median follow-up of 7.25 years in 14 cases, retiform hemangioendothelioma has
      proved to be a low-grade neoplasm that recurs frequently but has a very low
      metastatic rate. The single regional lymph node metastasis in this series was
      from a case with a biphasic pattern in which only the spindle cell component was
      represented in the metastasis. There have been no tumor-related deaths,
      underlining the importance of accurate distinction from conventional
      angiosarcoma. This distinction is facilitated principally by the absence of
      dissection between individual collagen bundles and the absence of endothelial
      atypia or mitotic activity. The precise relationship between retiform
      hemangioendothelioma and Dabska's tumor is uncertain, possibly because cases of
      the latter may not be homogeneous.

PMID- 8291651
TI  - Juvenile and adult xanthogranuloma. A histological and immunohistochemical
      comparison.
AB  - Thirteen cases of juvenile xanthogranuloma (JXG) and 13 cases of adult-type
      xanthogranuloma (AXG) were compared at the light and immunohistochemical levels.
      Histologically, four main cell types (vacuolated, xanthomatized, spindle-shaped,
      and "oncocytic") were seen in variable proportions (from monomorphous to mixed
      variants) with different types of giant cells (nonspecific, foreign body, Touton,
      and "ground-glass"). Giant cells were more prominent in AXG than in JXG;
      oncocytic cells (characterized by an eosinophilic, slightly granular cytoplasm
      similar to thyroid oncocytic cells) and mostly periodic acid-Schiff (PAS)
      negative giant cells with a ground-glass appearance (6 of 26) were not observed
      in classic JXG (i.e., occurring in children < 2 years old).
      Immunohistochemically, JXG and AXG gave similar results: most xanthogranuloma
      cells labeled strongly with KiM1P and vimentin, while HHF35 and HAM56 stained
      less intensively. Factor-XIIIa (FXIIIa), KP1 (CD68), and HAM56 stained mostly in
      the periphery of the lesions. Some markers gave variable results: peanut
      agglutinin (PA), 60%; alpha-1-antitrypsin, 50%; lysozyme, 25%; LN3 (HLA-DR), <
      10% of cells positive. Others were negative: S-100, MAC387 (L1 antigen), LeuM1
      (CD15), desmin, smooth muscle-specific actin, and QBEND10 (CD34). This profile
      helps to delineate xanthogranuloma from histological stimulants such as
      dermatofibroma (which is FXIIIa+, LN3+, KP1-, and PA-) and multicentric
      reticulohistiocytosis (which is FXIIIa-, KP1+, PA-, and HHF35-).

PMID- 8291652
TI  - Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical
      significance.
AB  - Sixty-four cases of interstitial pneumonia were identified that could not be
      classified into one of three main categories of idiopathic interstitial
      pneumonia. These cases, descriptively termed nonspecific interstitial
      pneumonia/fibrosis, were characterized by varying proportions of interstitial
      inflammation and fibrosis that appeared to be occurring over a single time span
      (i.e., the process was temporally uniform.) The most common presenting complaint
      was dyspnea for several months, and chest radiographs usually showed bilateral
      interstitial infiltrates. The prognosis was good with only five deaths due to
      progressive respiratory disease in 48 patients with known follow-up (11%). No
      deaths occurred in patients whose biopsies showed pure inflammation and no
      fibrosis. Nonspecific interstitial pneumonia must be separated from the three
      main forms of idiopathic interstitial pneumonia because of better prognosis and
      different treatment options. It should not be considered a specific disease,
      however, because it may have varying etiologies including underlying connective
      tissue diseases, organic dust or other exposures, and prior acute lung injury;
      less often, it may reflect a nonrepresentative biopsy of another process.

PMID- 8291653
TI  - Follicular dendritic cell tumors of the oral cavity.
AB  - Follicular dendritic cell tumors are uncommon, and all the reported cases have
      occurred as primary lymph node tumors. We report two cases in the oral cavity,
      one in the soft palate and one in the tonsil. The tumors were characterized by
      sheets, whorls, and storiform arrays of spindly and syncytial-appearing cells
      with oval nuclei, fine chromatin, distinct nucleoli, and occasional nuclear
      pseudoinclusions. Multinucleated forms were present and were prominent in one
      case. An unusual feature was the presence of irregular pseudovascular spaces,
      which could raise a concern for vascular neoplasm. Because the tumors showed
      cohesive growth and a sharp interface with the fibrous stroma, they could also be
      mistaken for carcinoma, sarcoma, or melanoma. After radiation therapy, the
      palatal tumor showed a greater degree of nuclear pleomorphism, numerous nuclear
      pseudoinclusions, and striking nuclear grooving and foldings, mimicking
      interdigitating reticulum cell tumors. The diagnosis in both cases was confirmed
      by immunoreactivity with CD21 and CD35 and by ultrastructural demonstration of
      interdigitating cell processes with desmosomes. Both tumors also showed
      unexpected immunoreactivity with muscle-specific actin. Follicular dendritic cell
      tumor merits wider recognition of its possible extranodal occurrence as well as
      its full morphological spectrum in order to better define its behavior.

PMID- 8291654
TI  - Immunohistochemical detection of cathepsin D in T2N0M0 breast carcinoma.
AB  - Recent studies have reported significant but inconsistent correlations between
      tumor cathepsin D (CD) concentration and prognosis in breast carcinoma. To
      investigate the tissue distribution and a prognostic utility of CD in breast
      carcinoma, 159 cases of T2N0M0 breast carcinoma with a minimum of 10 years'
      follow-up were studied for CD expression by immunohistochemistry. This group of
      patients was chosen for study because of current interest in prognostic markers
      for stage I breast carcinoma and the likelihood that there would be sufficient
      recurrences in this group to detect significant differences. Seventy-two
      carcinomas (45%) showed prominent staining of cells composing the tumor.
      Neoplastic cell staining for CD correlated with well-differentiated architecture,
      and lack of neoplastic cell CD expression correlated with high nuclear grade and
      the medullary carcinoma category. Stromal cell (primarily histiocyte) staining in
      carcinomas was the major contributor to CD expression in 67 of the 159 cases
      (42%). Intense intratumoral stromal cell staining correlated with absence of
      estrogen receptors and the medullary carcinoma subtype. There was no significant
      correlation between disease-free or overall survival and (a) intensity of overall
      staining for CD, (b) staining of carcinoma cells alone, or (c) staining of
      nonneoplastic cells within the region of the carcinoma. These results show that a
      significant proportion of CD activity detected within a tumor by
      immunohistochemistry may be contributed by nonneoplastic cells, and there is no
      significant correlation between survival and immunohistochemical detection of CD
      in T2N0M0 breast cancer.

PMID- 8291655
TI  - Tissue fragments recovered at cardiac surgery masquerading as tumoral
      proliferations. Evidence suggesting iatrogenic or artefactual origin and common
      occurrence.
AB  - The entity described in the literature as a "distinctive cardiovascular lesion"
      resembling histiocytoid hemangioma and more recently referred to as
      "mesothelial/monocytic incidental cardiac excrescence" may not be a true
      proliferative lesion. Rather, it may represent an artefact produced by suctioning
      of the pericardial cavity during cardiac surgery. This hypothesis was explored by
      comparing two index cases of cardiac histiocytoid hemangioma-like lesions (HLLL)
      to (a) the contents of extracorporeal bypass pump (ECBP) filters in 22 random
      cardiac surgical cases, and (b) material adherent to mediastinal and pericardial
      drains in 15 random post-cardiac surgery cases. In 18 of the 22 ECBP filter cases
      (82%) and two of the 15 postsurgery cases (13%), tissue fragments
      indistinguishable from the HHLL index cases were identified. These filter and
      drain fragments had light microscopic, immunohistochemical, and ultrastructural
      features identical to those of the index cases, as well as to the HHLLs described
      in the literature. In neither index case, nor in the study patients, were any
      proliferative lesions identified at surgery. Three study cases subsequently came
      to autopsy, and no proliferative lesions were found. This and other evidence
      strongly suggest that these lesions not only are artefactual, but also are a
      common occurrence. They are likely produced during cardiac surgery by the
      cardiotomy suction, with compaction of friable mesothelial strips, other tissue
      debris, and fibrin into tumor-like fragments that may be transported around the
      operative site on the suction tip.

PMID- 8291656
TI  - Primary glomerulonephritis with detectable glomerular hepatitis B virus antigens.
AB  - The glomerular pathology and hepatitis B virus (HBV) antigens in renal biopsies
      were investigated in 100 consecutive patients with both primary
      glomerulonephritis and positive serology for hepatitis B surface antigen (HBsAg).
      Glomerular HBV antigens including HBsAg, hepatitis B core antigen (HBcAg), and
      hepatitis B e antigen (HBeAg) were examined in frozen tissue using both
      polyclonal and monoclonal antibodies. HBV serology and glomerular antigens were
      correlated. Using monoclonal antibodies, at least one of the three HBV antigens
      was detectable in glomeruli in 39% of the cases. These findings correspond mainly
      to detectable glomerular HBsAg and HBeAg in 22.3 and 28.4% of cases,
      respectively. A good correlation was found between glomerular and serum HBeAg but
      not observed for HBsAg. Serum HBcAg was not examined and not correlated with
      glomerular staining. When the diagnosis of HBV-related glomerulonephritis was
      based strictly on detectable glomerular antigens, three distinctive morphologies
      were identified: membranous nephropathy, mesangiocapillary glomerulonephritis,
      and mesangial proliferative glomerulonephritis with immunoglobulin A (IgA)
      deposits (IgA nephropathy). Each of these lesions may be seen in pure form or
      occasionally in overlapping form leading to double glomerulopathies. Glomerular
      HBeAg and HBsAg were associated with subepithelial and mesangial immune
      complexes, respectively. Rare overlap between membranous nephropathy and IgA
      nephropathy further emphasized the distinctive pathology of HBV-related
      glomerulonephritis and the independent etiological role of HBeAg and HBsAg. In
      other glomerulonephritis, which rarely demonstrated glomerular HBV antigens, the
      pathogenetic role of chronic HBV infection remains to be proven.

PMID- 8291657
TI  - Renal myxoma. A report of two cases and review of the literature.
AB  - Renal myxomas are rare neoplasms. Seven cases have been reported, of which only
      two are convincingly diagnosed as myxoma; the remaining cases exhibit features of
      sarcoma, fibroepithelial polyp, or myxolipoma. We report two additional cases;
      one in a 52-year-old man and another in a 68-year-old woman. They were discovered
      incidentally by radiological examination. The resected kidney in both patients
      contained a well-demarcated gelatinous intraparenchymal tumor, which consisted of
      occasional slender spindle cells scattered in an abundant myxoid stroma, closely
      resembling myxomas of other sites. The tumor cells showed immunoreactivity for
      vimentin but not for S-100 protein, epithelial membrane antigen (EMA), CAM 5.2,
      HHF-35, or smooth muscle actin. Ultrastructural features were of fibroblast-like
      cells with an elaborate network of cytoplasmic processes. The differential
      diagnosis of myxoid tumors of the kidney includes myxoid variants of renal
      sarcomas and carcinomas, renomedullary interstitial cell tumors, and
      fibroepithelial polyps. It is important to recognize the existence of a renal
      myxoma, to avoid confusing this benign tumor with the malignant neoplasms with
      secondary myxoid features that may involve the kidney.

PMID- 8291658
TI  - Reactive eosinophilic pulmonary vascular infiltration in patients with
      spontaneous pneumothorax.
AB  - Prominent nonnecrotizing eosinophilic inflammation of muscular pulmonary arteries
      was seen in resected lung tissue from two patients with spontaneous pneumothorax.
      Other histologic features included reactive eosinophilic pleuritis (REP) and
      fibrobullous disease. Eosinophilic vascular infiltration was not contiguous to
      REP. In neither patient was there a specific and recognized cause of eosinophilic
      vasculitis. Both patients are without pulmonary symptoms 1 and 4 years after
      pneumothorax. Eosinophilic vascular infiltration initially suggested the
      diagnosis of allergic angiitis or pulmonary eosinophilic granuloma. These
      diagnoses were excluded by clinical and morphologic data. We subsequently
      reviewed 30 cases of lung tissue resected from patients with pneumothorax and
      found REP in 18 patients (60%) and mild pulmonary vascular and perivascular
      eosinophilia in five patients (17%). REP was present in all cases with
      eosinophilic vascular infiltration. We conclude that this eosinophilic vascular
      lesion is an unusual reaction in patients with REP and pneumothorax. Occasionally
      this lesion mimics allergic angiitis or eosinophilic granuloma. The pathogenesis
      is probably related to vascular transport of eosinophils to the injured pleural
      surface.

PMID- 8291659
TI  - Mucin-secreting adenocarcinoma of the prostate with neuroendocrine
      differentiation and Paneth-like cells.
AB  - We present an unusual variant of prostatic adenocarcinoma with obvious mucinous
      and neuroendocrine features, arising in the transition zone. The neuroendocrine
      component is largely represented by Paneth-like cells (PLCs). These cells
      correspond to previously described eosinophilic cells and are amphicrine. We
      could demonstrate immunohistochemically the presence of calcitonin in some of
      these PLCs. The prognostic significance of these special characteristics is not
      well known, but it is most likely that this type of prostate cancer will not
      respond well to hormonal therapy.

PMID- 8291660
TI  - Lauren V. Ackerman, M.D.

PMID- 8291661
TI  - Proposed Bethesda System.

PMID- 8291662
TI  - Eosinophilic and lymphoeosinophilic cholecystitis.

PMID- 8291663
TI  - [The treatment of carcinoma of the pyriform sinus at Santa Creu I Sant Pau
      Hospital of Barcelona. The role of surgery].
AB  - The paper deals with the retrospective review done by the AA. about the
      treatments used for squamous carcinomata of the pyriform sinus at Santa Creu i
      Sant Pau Hospital, Barcelona, between the years 1984-1990. In this term 76 sinus
      pyriform carcinomata were diagnosed, 12 of which (16%) were managed palliatively.
      In the other 64 cases radical treatment was advised and followed: 5 cases
      underwent radical cobalt-therapy; polychemotherapy followed by radiotherapy in
      27; surgery plus radiotherapy in 7; and polychemotherapy completed with surgery
      and radiotherapy in the remaining 25 cases. Considerations on the realized
      pharyngectomies and their reconstructive steps and complications are commented.
      Inventory and end results in each group are reported. The beneficial local
      influence was evident when surgery was employed (100% with surgery plus
      radiotherapy and 92% with polychemotherapy, surgery and radiotherapy). Local
      control was inferior if surgery was discarded (20% in radiotherapy and 37% by
      polychemotherapy followed by radiotherapy). Actuarial survival for the lump sum
      amounted for the 40 percent after 5 years follow-up. It must be emphasized that
      these groups are not comparable because the choice treatment in each case was
      indicated in view of the initial stage.

PMID- 8291664
TI  - [Microbiology of acute external otitis in our environment].
AB  - The paper deals with the review done by the AA. about the microbiology of 135
      acute diffuse external otitis cases, treated at their Department in one year
      term. In the series is emphasized the seasonal distribution, steadily uniform in
      the studied period, being the Pseudomonas aeruginosa and Candida albicans the
      paramount responsible for these otitis.

PMID- 8291665
TI  - [Pyolaryngocele as a focal disease].
AB  - Report of one case of Laryngocele in a 49 years old male, without previous
      anamnestic data, but urticaria and orchitis recurrens till the removal of the
      pyolaryngocele. The diagnosis was awkward because of its rare behaviour with
      torpid evolution and distant manifestations. The AA. think it was consistent with
      a septic focus.

PMID- 8291666
TI  - [Pneumocephalus as a complication of mastoid surgery].
AB  - Non-traumatic otologic diseases are a rare cause of Pneumocephalus. Among them
      few reports have been published whereas it presented following oto-surgery. The
      AA. communicate one of those events in a patient who presented with CSF-otorrhea,
      headache and disorientation after recent radical mastoidectomy. The definitive
      diagnosis was done by CT-scan imaging. Survey of the scarce literature on the
      subject, description of the clinical and diagnostic features, its possible
      physiopathology and surgical management.

PMID- 8291667
TI  - [Appraisal of diagnostic methods in surgical pathology of the thyroid gland].

PMID- 8291668
TI  - [Otomycosis: a microbiological study of 147 cases of otitis externa].
AB  - An accurate and systematic myco- and bacteriological appraisal of each case,
      should comport the lowering of wrong diagnosis and also therapeutic failures in
      those patients. The target of the AA. is to verify the frequency and the
      identification as well, of bacteria and/or fungi, unique or in association,
      responsible for the otitis. And the objective is to start with the most
      appropriate treatment in spite of the laboratory answer and also to schedule a
      laboratory protocol to follow in suspected cases of otomycosis.

PMID- 8291669
TI  - [Melanoma of the nasal cavity].
AB  - Presenting a case of nasal Melanoma, in a patient previously diagnosed and
      treated from Rhabdomyosarcoma of the same nasal cavity. In our Department has
      been treated with surgery plus thymostimulin (TP-1 Serono) after surgery. Subject
      reviewed and clinic features, diagnostic difficulties and nowadays immunotherapy
      commented.

PMID- 8291670
TI  - [Foreign bodies in ENT analysis after one year's assistance].
AB  - Foreign bodies sitting in the E.N.T.-area are the most urgencies needing
      immediate attention by the specialist. The AA. study the 738 cases admitted at
      their Department, for correlative consultations, in one year-term, because of
      suspicion of accidental lodgements. They arrange the whole lot in 5 not specific
      localizations, with the aim of consider the peculiarities of each group. In the
      great deal of instances the patients were worried for oropharyngeal penetration,
      followed by a lower number complaining of oesophageal distress. Considerations
      regarding the usefulness of ancillary exploratory techniques, specially the
      Radiology.

PMID- 8291671
TI  - [Castleman's lymphoma of the neck].
AB  - We present a case of Castleman's disease (hyaline-vascular type) localized in the
      neck, confirmed by histopathological examination. A review of the illness is also
      reported.

PMID- 8291672
TI  - Basic matrices for the matrix-assisted laser desorption/ionization mass
      spectrometry of proteins and oligonucleotides.
AB  - In order to examine the importance of pH in the matrix-assisted laser
      desorption/ionization (MALDI) analysis of proteins and oligonucleotides, 37
      highly substituted pyrimidine, pyridine, and benzene derivatives containing basic
      amino groups were screened as potential matrices. Several of these compounds were
      useful for the preparation and analysis of samples under neutral and basic pH
      conditions. The matrix, 2-amino-4-methyl-5-nitropyridine, gave good results with
      small proteins (up to approximately 12,000 Da). The best results with
      oligonucleotides were obtained with 2-amino-5-nitropyridine, which was a useful
      matrix for the analysis of mixed-base oligonucleotides smaller than 20
      nucleotides in length and homopolymers of thymidine. In general, oligonucleotide
      analysis using basic matrices was found to be subject to similar constraints of
      size and base composition that hold when acidic matrices are used. A major
      advantage of these newly discovered matrix materials over the more commonly used
      acidic matrices is that they extend the utility of MALDI to the analysis of acid
      sensitive species.

PMID- 8291673
TI  - DNA sequencing by capillary electrophoresis: use of a two-laser-two-window
      intensified diode array detection system.
AB  - This paper presents the principles of an instrument designed for DNA sequencing
      using the standard four-dye-labeled primer approach. The method is based on
      capillary electrophoresis with laser-induced fluorescence and an intensified
      diode array detector. An important goal of the instrument design has been a
      detection system that possesses high sensitivity and high spectral resolution.
      Based on an analysis of the spectral characteristics of the four standard dye
      labeled primers, FAM, JOE, ROX, and TAMRA, the strategy has been to use a two
      laser-two-window approach, in which a 488-nm argon ion laser illuminates one
      window, followed by a 543-nm helium-neon laser illuminating the second window.
      The two-window approach has no moving parts and permits continuous illumination.
      Spectral resolution is provided by a grating spectrograph and a cooled
      intensified diode array. The estimated limit of detection for the standard four
      dye-labeled primers was found to be in the sample concentration range of 1 x 10(
      12) M. To achieve these low levels, complete free-radical polymerization of
      polyacrylamide has been found to be necessary in order to reduce background
      noise. In addition, reduction in background noise was accomplished by continual
      purging of the anodic reservoir in order to prevent electrolysis products from
      entering the capillary. Separation of DNA sequencing reaction products is
      demonstrated on a 9% T linear polyacrylamide column.

PMID- 8291674
TI  - Comparison of a monoclonal antibody-based enzyme-linked immunosorbent assay and
      gas chromatography for the determination of nicotine in cigarette smoke
      condensates.
AB  - A competitive enzyme-linked immunosorbent assay (ELISA) based on monoclonal
      antibodies was developed to measure nicotine in smoke condensates of cigarettes.
      The ELISA standard curve displays a detection limit of 70 ng/mL and an effective
      working range of 0.3-4.0 micrograms of nicotine/mL. Using standard samples, ELISA
      results compare well with theoretical values (r = 0.997). The suitability of the
      method for industrial routine application was evaluated by measuring the nicotine
      concentration in 245 cigarette smoke condensates. When ELISA results were
      compared with those obtained by gas chromatography, a correlation coefficient r =
      0.886 was obtained. The assay allows the specific, precise, and accurate
      determination of nicotine, without any significant interference from other
      alkaloids also present in tobacco smoke. Preliminary data suggest that the
      immunoassay could also be applied to other matrices, e.g., tobacco extracts.
      ELISA equipment requirements are minimum, simple, and low-cost, and an unskilled
      person could perform 150 analysis in a working day. On the basis of these
      features, ELISA is proposed as a promising alternative to instrumental methods
      for some industrial applications.

PMID- 8291675
TI  - Determination of cholesterol and cholesterol ester with novel enzyme
      microsensors.
AB  - Enzyme microsensors using cholesterol oxidase (EC 1.1.3.6) and cholesterol
      esterase (EC 3.1.1.13) were developed for measuring cholesterol and cholesterol
      ester. The platinum microsensors (platinum diameter, 50 microns) were etched in
      hot aqua regia to create a cavity at their tip. A porous composite material
      prepared from acetylene black and Teflon emulsion was packed into this cavity and
      the redox mediator [Os(bpy)3](PF6)2 was monitored by cyclic voltammetry in the
      potential range of 200-900 mV. The microsensors were dipped overnight in buffer
      solution containing the desired enzyme to immobilize it on the tip by adsorption.
      Calibration curves for measurements of cholesterol and cholesterol ester, the
      effects of pH, temperature, and concomitant compounds, the lifetime of the
      microsensors, and their availability for measuring cholesterol and cholesterol
      ester in urine were examined. Under optimal conditions, the response of the
      sensors was linear in concentration ranges of 5 microM-0.47 mM cholesterol and 2
      microM-1.00 mM cholesterol ester.

PMID- 8291676
TI  - Biomagnetic neurosensors.
AB  - In this report we demonstrate the first analytical application of biomagnetic
      field detection at nerve fibers for biosensing purposes. A ferrite core toroid
      surrounding the nerve, coupled to a low-noise, low-input-impedance amplifier, is
      used to inductively detect the compound action current (CAC) in crayfish giant
      axons upon stimulation of nerve firing. Detection of the local anesthetic
      lidocaine, which blocks neuronal conduction by binding in the ion channel of the
      voltage-gated sodium channel receptor, is achieved by monitoring the
      disappearance of the CAC. The application of this novel detection principle to
      the screening of neurotoxic and neuromodulatory drugs and natural product
      extracts is proposed.

PMID- 8291677
TI  - Electrophoretically mediated microanalysis of leucine aminopeptidase in complex
      matrices using time-resolved laser-induced fluorescence detection.
AB  - Leucine aminopeptidase, a clinically significant enzyme, was assayed in complex
      biological samples using a new technique termed electrophoretically mediated
      microanalysis. The assay was performed in capillary electrophoresis columns using
      time-resolved laser-induced fluorescence detection. Human serum, human urine, and
      Escherichia coli supernatant samples were assayed using this method. Results for
      serum and urine were within the ranges of expected values found in the
      literature. A low concentration of 6 x 10(-13) M enzyme in buffer was detected
      using this method. A detection limit (3 sigma) of 400 enzyme molecules in buffer
      was determined.

PMID- 8291678
TI  - Near-infrared spectroscopic measurement of glucose in a protein matrix.
AB  - A method is described for measuring clinically relevant levels of glucose in a
      protein matrix by near-infrared (near-IR) absorption spectroscopy. Results from
      an initial screening of major blood constituents identify protein as a major
      potential interference to the near-IR measurement of glucose in blood. The
      interference by protein is caused by relatively high concentrations coupled with
      strong near-IR absorption bands between 5000 and 4000 cm-1 (2.0-2.5 microns).
      Calibration models based on a simple univariate calibration procedure are not
      capable of providing accurate glucose concentrations from an independent set of
      prediction spectra. By use of the multivariate technique of partial least squares
      (PLS) regression, glucose concentrations can be determined with a 0.35 mM (6.3
      mg/dL) standard error of prediction. The spectral range for this calibration
      model extends from 4600 to 4200 cm-1, and the optimum number of PLS factors is
      14. In addition, calibration models based on a combination of digital Fourier
      filtering and PLS regression have been constructed and evaluated. Superior
      calibration models are obtained by using a preprocessing digital filtering step
      to remove spectral features not associated with glucose. The best overall
      calibration model was obtained by using a Gaussian-shaped Fourier filter defined
      by a mean position of 0.03f and standard deviation of 0.007f coupled with a 12
      factor PLS regression computed over the spectral range from 4600 to 4200 cm-1.
      This model provided a standard error of prediction of 0.24 mM (4.3 mg/dL) for an
      independent set of prediction spectra.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291679
TI  - Strategies for coupling digital filtering with partial least-squares regression:
      application to the determination of glucose in plasma by Fourier transform near
      infrared spectroscopy.
AB  - Protocols are established for coupling digital filtering techniques with partial
      least-squares (PLS) regression for use in constructing multivariate calibration
      models from Fourier transform near-infrared absorbance spectra. Calibration
      models are developed to predict glucose concentrations in bovine plasma samples.
      Employing a calibration data set of 300 spectra collected from 55 plasma samples
      and 3 plasma lots, individual calibration models are developed based on four
      spectral ranges selected from the region 5000-4000 cm-1. A separate test set of
      69 spectra collected from 14 plasma samples is used to evaluate the computed
      models. Gaussian-shaped bandpass digital filters are implemented by use of
      Fourier filtering techniques and employed to preprocess spectra to remove
      variation due to the background absorbance of the plasma matrix. PLS regression
      is used with the filtered spectra to compute calibration models for glucose. The
      optimization of the filter bandpass parameters is explored through the use of
      response surface methods. Through these optimization studies, calibration models
      are developed that achieve standard errors of estimate and standard errors of
      prediction in the range 0.4-0.5 mM across the concentration range of 2.5-25.5 mM.
      It is determined that the use of digital filtering as a preprocessing step
      significantly improves the performance of the resulting calibration models,
      minimizes the importance of spectral range in the calibration model development,
      and reduces the required number of PLS factors in each model.

PMID- 8291680
TI  - Use of a regenerable immobilized second antibody to determine azidothymidine in a
      flow system.
AB  - A regenerable immobilized second-antibody reactor was used to measure
      azidothymidine (AZT) by competitive enzyme immunoassay in a flow system. The
      immobilized antibody was regenerated 4 times with little loss of
      immunospecificity. A residual enzymatic activity of about 7% of the total
      response was obtained with horseradish peroxidase as label. AZT was measured
      below the nanomolar level by allowing competition to proceed for about 2 min. A
      limit of detection of 6.57 x 10(-11) +/- 1.56 x 10(-11) M AZT was obtained when
      the concentration of AZT-peroxidase conjugate was 0.125 ng/mL. This system was
      used to determined azidothymidine in Retrovir capsule with good results. In
      replicate measurements, RSDs of 5.51% and 2.44%, n = 6, were obtained at 7.48 x
      10(-11) and 3.74 x 10(-9) M AZT, respectively.

PMID- 8291681
TI  - Continuous electrophoretic separations in narrow channels coupled to small-bore
      capillaries.
AB  - Continuous zone electrophoretic separations in channels have been demonstrated.
      This new technique has the potential to continuously sample and separate analytes
      from volume-limited microenvironments. A small-bore capillary is used to
      electrophoretically sample, but not separate, a mixture of dansylated amino
      acids. The capillary is coupled to a quartz channel structure in a manner which
      allows continuous injection of the sampled material into the channel. The channel
      functions to continuously separate the sampled material via electrophoresis. A
      laser-induced fluorescence detection scheme, which involves two fiber optic
      arrays situated at the channel exit, monitors eluting analytes. A continuous
      separation of dansylated amino acids on the time scale of a few minutes
      demonstrates the utility of the technique. Sampling has been performed
      continuously up to 400 s, and initial detection limits are approximately 30
      microM.

PMID- 8291682
TI  - Presence and foveal enrichment of rod opsin in the "all cone" retina of the
      American chameleon.
AB  - The retinal photoreceptors of the eye of the American chameleon, Anolis
      carolinensis, have been considered to be exclusively cones. Its retina is unusual
      for possessing two foveas (areas associated with heightened visual acuity), with
      the major, central fovea deeply incised and very densely packed with
      photoreceptors. Immunoblotting and light- and electron microscopic
      immunocytochemistry, using several opsin monoclonal antibodies previously found
      specific for rods, demonstrated the presence and localization of this protein in
      the Anolis retina. This visual pigment appears sparsely in a subpopulation of
      photoreceptors in the periphery but overwhelmingly in the central fovea.
      Complementary results with cone-specific antibody and lectin binding corroborated
      this spatial organization. These results, as well as those with geckos, suggest
      that photoreceptor morphology is not an accurate guide among the lacertilians to
      visual pigment content, and that this phylogenetic grouping may constitute a
      crossroads in vertebrate photoreceptor evolution.

PMID- 8291683
TI  - Structure of the Golgi apparatus in stimulated and nonstimulated acinar cells of
      mammary glands of the rat.
AB  - The structural features of the Golgi apparatus of acinar cells of mammary glands
      were examined with the electron microscope in 3 groups of rats: (1) in lactating
      female animals at 8 days postpartum, which served as controls; (2) in female rats
      sacrificed at various intervals from 2 to 30 hours following separation from
      their 8-day old pups; and (3) in females separated from their 8-day-old pups for
      a period of 12 hours and returned to their litters for durations of 1, 2, 4, and
      8 hours. In animals of group 2, the Golgi stacks remained identical to that of
      controls between 2 and 8 hours. At 12 hours and later, the Golgi stacks decreased
      progressively in size, but the number of elements composing the stacks remained
      similar to that of lactating females and all contained casein submicelles. At 24
      and 30 hours, typical secretory granules containing casein micelles disappeared
      from the trans aspect of the stacks. The earliest and most striking changes
      observed in the Golgi apparatus of the rats of group 2 took place at 12 hours. At
      this time, the prosecretory and secretory granules decreased considerably in
      volume and lost most of their electron-lucent content. This indicated that the
      delivery of small molecules, i.e., lactose and H2O, to these structures was soon
      altered following arrest of the sucking stimulus. In animals of group 3, the size
      of prosecretory and secretory granules and the amount of their electron-lucent
      content reverted to normal at 4 hours. Thus the influx of lactose and H2O into
      these structures appears to be rapidly restored after returning the pups to their
      mothers. The decrease in size of the Golgi stacks noted at 12, 18, and 24 hours
      following arrest of lactation (group 2), was accompanied by an increase in number
      of small vesicles that formed clusters next to the Golgi stacks and in "wells."
      Thus in these regressing Golgi stacks, many of the associated small vesicles
      appear to arise by vesiculation of the saccules.

PMID- 8291684
TI  - Striated anchoring fibrils-anchoring plaque complexes and their relation to
      hemidesmosomes of myoepithelial and secretory cells in mammary glands of
      lactating rats.
AB  - Striated anchoring fibrils (SAF) are associated with the basement membrane
      underlying myoepithelial and acinar cells of mammary glands. Their proximal
      extremities are inserted in electron-dense areas of the lamina densa, the
      anchoring plaques seen facing the hemidesmosomes of both myoepithelial and acinar
      cells. In the case of myoepithelial cells, the hemidesmosomes show a thick
      cytoplasmic plaque applied to the basal plasma membrane in which cytoplasmic
      filaments are inserted. Facing this plaque but on the extracellular aspect and at
      a short distance of 5-10 nm, there is a thin layer of electron-dense nodular
      material called the subcell membrane plate, which is connected to the plasma
      membrane by short filamentous bridges. Between this subcell membrane plate and
      the anchoring plaque, there is an abundance of fine anchoring filaments crossing
      the lamina lucida. Such anchoring filaments are less abundant in the lamina
      lucida outside the hemidesmosomal areas. In the case of acinar cells, the
      cytoplasmic plaques of the hemidesmosomes are thin and the associated cytoplasmic
      filaments less conspicuous. No distinct subcell membrane plate is seen on the
      extracellular aspect of the plasma membrane facing the cytoplasmic plaque of the
      hemidesmosomes. However, in this area numerous anchoring filaments cross the
      lamina lucida between the plasma membrane and the SAF-anchoring plaque complex.
      The abundance, in these cells, of hemidesmosomes and their association with SAF
      anchoring plaque complexes seen in the basement membrane must constitute a strong
      attachment for both myoepithelial and acinar cells and bind them to the
      underlying collagen fibrils, thus preventing their detachment from the connective
      tissue during the contractions of myoepithelial cells during milk ejection.

PMID- 8291685
TI  - Short-term oral phosphate and bone remodeling in beagles.
AB  - Attempts to increase bone volume in osteoporotic patients are still in the
      experimental stage. The coherence therapy, proposed by Frost, suggests that the
      activated bone units can remodel bone matrix in tandem. The cells (i.e.,
      osteoclast and osteoblast which compose the remodeling units) are manipulated
      through specific medications timed to each of their duration of actions. The
      current study was to examine the effect of withdrawal of oral phosphate on bone
      in ovariectomized dogs. The present report demonstrates the capability of short
      term oral phosphate to activate bone remodeling in the ovariectomized animal
      model. Results from biochemical and histomorphometric analyses confirm that
      remodeling units are activated following the release of parathyroid hormone. This
      transient scenario inflicts a shift of mineral density distribution in cancellous
      bone matrix of the iliac crest. Nevertheless, the bone remodeling units appear to
      be synchronized with each other and thus their resorptive and formative phases
      should be amenable to further pharmacological manipulation.

PMID- 8291686
TI  - Endothelin-1 localization in bone cells and vascular endothelial cells in rat
      bone marrow.
AB  - Endothelin-1 (ET-1) localization in bone cells and associated vascular
      endothelial cells in metaphyseal bone marrow of the rat femur was examined by a
      biotin-streptoavidin-horseradish peroxidase method in paraffin sections and by
      indirect immunogold techniques in post-embedded ultrathin sections. Mouse anti-ET
      1 monoclonal antibody was used as the primary antibody. In metaphyseal bone
      marrow, intense immunostaining was observed over osteoclasts, osteoblasts, young
      osteocytes, and vascular endothelial cells. But bone and cartilage matrices and
      chondrocytes in the proliferating zone were negative for immunoreaction. At the
      subcellular level, specific immunogold labeling was localized along plasma
      membranes and in the cytoplasm including those of ruffled borders and clear zones
      of osteoclasts. Some colloidal gold particles were also detectable within pale
      vacuoles of osteoclasts. Immunoreactivity was also found along the plasma
      membranes, cisterns of rough-surfaced endoplasmic reticulum, mitochondria, and
      cytoplasmic matrices of osteoblasts, but was less intense than that of
      osteoclasts. In endothelial cells of blood capillaries in close proximity to bone
      cells, intense immunolabeling occurred over the cytoplasm. None of the cases
      examined showed accumulation of immunogold particles in the secretion granules of
      these cells.

PMID- 8291687
TI  - Three-dimensional cytoarchitecture of complex branched fibers in soleus muscle
      from mdx mutant mice.
AB  - Three-dimensional cytoarchitecture and types and features of muscle fibers were
      examined in soleus muscles from mdx mutant mice at different stages of
      development. In the 2-week-old mice, no abnormal muscle fibers were observed
      light microscopically, whereas in the 4-week-old animals, disrupted fibers were
      frequent in light microscopy and scanning electron microscopy. Muscle fibers
      fused with several short fiber branches appeared at the sixth week after birth
      and increased in number until the tenth week. In the 1-year-old mice,
      approximately ten or more muscle fibers were seen fused together. They had many
      complex branches forming an "anastomosing syncytial reticulum." Muscle fibers
      with irregular diameters and aggregations of the same type fibers were also
      observed. Our results demonstrated that these complex branched fibers might be
      formed by long term repetition of the degeneration and regeneration cycle during
      the development of soleus muscles, indicating that the characteristic features of
      muscle fibers with irregular diameters and aggregations of the same type fibers
      are certainly dependent on the existence of the complex branched fibers.

PMID- 8291688
TI  - Structure, innervation, and age-associated changes of mouse forearm muscles.
AB  - In spite of a decline in muscle strength with age, the cause of the overall
      decrease in motor performance in aged mammals, including rodents, is incompletely
      understood. To add clarity, the gross organization, innervation, histochemical
      fiber types, and age-associated changes are described for mouse forearm muscles
      used in a variety of motor functions. The anterior (flexor) and posterior
      (extensor) forearm compartments have the same arrangement of muscles and gross
      pattern of innervation as the rat. Two primary histochemical fiber types,
      fast/oxidative/glycolytic (FOG) and fast/glycolytic (FG), with characteristic
      histochemical staining patterns were observed in all forearm muscles.
      Additionally, there was a small population of slow/oxidative (SO) fibers confined
      to the deep region of a single muscle, the flexor carpi ulnaris (FCU). Between 18
      and 26 months the FCU muscle displayed fibers with morphological features
      distinct from earlier ages. Fibers displayed a greater variation in size, a loss
      of their uniform polygonal shape, and a dramatic increase in clumps of
      subsarcolemmal mitochondria, lysosomes, and lipofuscin granules. Many of the
      fibers had a distinctly atrophic, angular shape consistent with recent
      denervation. Morphometric analyses of the FCU's source of innervation, the ulnar
      nerve and one of its ventral roots (C8), were consistent with the denervation
      like changes in the muscle fibers. Although, there was no net loss of myelinated
      axons between 4 and 26 months of age, there was a significant increase in the
      density of degenerating cells in both the ulnar nerve and ventral root C8.

PMID- 8291689
TI  - Transport pathways for macromolecules in the aortic endothelium. II. The
      distribution analysis of plasmalemmal vesicles reconstructed by serial sections.
AB  - Three-dimensional organization of vesicles was examined to elucidate the
      transendothelial transport properties for macromolecules in rat aortic
      endothelium using ultrathin serial sections and horseradish peroxidase (HRP) as a
      tracer molecule. A total number of reconstructing vesicles was 1,298 in nine
      series of serial electron micrographs, if each vesicular entity was counted as
      one regardless of composite number of vesicles. The vesicles could be classified
      into the following six types: HRP-positive luminal, abluminal and intercellular
      invaginations; HRP-positive channels; HRP-positive and -negative vesicles. The
      vesicular invaginations and the channels occupied 97.8% and 0.9% of the total
      vesicles, whereas HRP-positive and -negative free vesicles were found in 0.8% and
      0.5%, respectively. The average numerical density of the luminal invagination was
      41.1/microns 2 and approximately equal to that of the abluminal invagination
      (42.0/microns 2), whereas the frequency of the latter was 1.4 times higher than
      that of the former since the abluminal surface of the endothelium was more
      irregular to increase a surface area. Each endothelial region varied in the
      vesicular density and the peripheral region generally showed the higher density,
      although the transendothelial channels composed of vesicles were not always found
      in every peripheral region. These results suggest that the shuttle hypothesis is
      unsuitable to explain "vesicular transport" in the arterial endothelium as well
      as in the capillary endothelium and that the channels in the peripheral region
      mainly control transendothelial transport for macromolecules via vesicles.

PMID- 8291690
TI  - Glucocorticoid regulation of surfactant-associated proteins in rabbit fetal lung
      in vivo.
AB  - The effects of a maternally administered synthetic glucocorticoid, betamethasone,
      on the levels of mRNA for the surfactant proteins SP-A, SP-B, and SP-C and on the
      levels of SP-A protein were investigated in day 27 gestational age rabbit fetal
      lung tissue. Betamethasone administration to the pregnant rabbit caused
      approximately a twofold increase in the fetal lung level of SP-A protein and a
      threefold increase in fetal lung SP-A mRNA levels when compared to levels in
      fetuses obtained from saline-treated or uninjected animals. SP-B mRNA was
      increased fourfold in fetal lung tissue obtained from glucocorticoid-treated
      pregnant does when compared to levels in fetuses of uninjected pregnant does.
      However, SP-B mRNA levels in fetal lung tissue from saline-injected controls were
      also significantly elevated, approximately twofold, when compared to fetal lung
      SP-B mRNA levels in the uninjected control condition. SP-C mRNA levels in lung
      tissue of fetuses from both saline-injected and betamethasone-injected pregnant
      does were increased similarly, approximately twofold, over SP-C mRNA levels in
      fetal lung tissue obtained from uninjected control does. These data are
      suggestive that betamethasone treatment increases fetal lung SP-A and SP-B mRNA
      levels and that maternal stress alone can increase the expression of SP-B and SP
      C mRNA in rabbit fetal lung tissue. Using in situ hybridization, SP-A mRNA was
      shown to be present primarily in alveolar type II cells in fetuses of control and
      saline-injected does. However, SP-A mRNA was easily detected in both alveolar
      type II cells and bronchiolar epithelial cells of rabbit fetal lung tissue
      following maternal betamethasone treatment. In contrast, SP-B and SP-C mRNA were
      present only in alveolar type II cells of lung tissue obtained from fetuses of
      control, saline, or betamethasone-treated does. Thus maternal administration of
      glucocorticoids increased SP-A protein as well as SP-A and SP-B mRNA levels in
      rabbit fetal lung tissue. SP-A mRNA was localized to both alveolar type II cells
      and in smaller amounts in bronchiolar epithelial cells of rabbit fetal lung
      tissue. However, SP-B and SP-C mRNA were detected only in alveolar type II cells.

PMID- 8291691
TI  - Experimental study of the development of the truncus arteriosus of the chick
      embryo heart. I. Time of appearance.
AB  - The time of appearance of the truncus arteriosus was studied in the chick embryo
      using an in ovo labeling technique. Three hundred embryos at stages 13-18 of
      Hamburger and Hamilton were selectively labeled at the distal end of the heart
      tube, using gelatine-india ink label; 122 of these embryos were reincubated and
      111 of them reached stages 25-28. In these stages the final location of the label
      was determined. Only 95 of these embryos showed both a normal heart and a label
      located in it. The remaining embryos were discarded due to abnormal cardiac
      morphology or because the label was not found. Embryos labeled at stages 13-14
      had label in the conus in 42.8% of the cases and in the boundary between the
      conus and the truncus arteriosus in 57.1% of the cases. Label placed at stages 15
      16 was located in the conus in 6.1% of the cases, in the boundary between the
      conus and the truncus arteriosus in 44.8% of the cases, and in the truncus
      arteriosus in 48.9% of the cases. Finally, label placed at stages 17-18 was
      located in the boundary between the conus and the truncus arteriosus in 18.7% of
      the cases and in the truncus arteriosus in 81.2% of the cases. Our results permit
      us to conclude that the truncus arteriosus appears in the chick embryo as early
      as stages 15-16 of Hamburger and Hamilton (50-56 hours of incubation).

PMID- 8291692
TI  - Cardiac neural crest contribution to the pulmonary artery and sixth aortic arch
      artery complex in chick embryos aged 6 to 18 days.
AB  - Previous studies of cardiac neural crest (CNC) migration in early chick embryos
      demonstrated CNC cells in the media of pharyngeal arch arteries three, four, and
      six, and in the most proximal part of the developing pulmonary arteries. The
      objectives of this study were to learn 1) to what extent the CNC is involved in
      the later development of the pulmonary arteries, 2) how the CNC cells are
      distributed in the sixth aortic arch artery including the wall of the ductus
      arteriosus in the older embryo, and 3) what happens to the CNC as the pulmonary
      artery/sixth arch complex grows into its adult configuration. Quail-to-chick
      chimeras were used to study CNC distribution in embryos aged 6 to 18 days.
      Controls (undisturbed chick embryos) were collected with chimeras. Each was
      fixed, processed, sectioned, stained with Feulgen-Rossenbeck stain, and analyzed.
      The results demonstrated that CNC disappeared from the proximal pulmonary
      arteries by embryonic day 9 and played no further role in pulmonary artery
      development. With the exception of the endothelium, CNC completely filled the
      wall of the sixth aortic arch artery as far distally as its junction with the
      dorsal aorta in younger embryos and with the aorta in older embryos, thus
      suggesting the possibility of proximodistal migration of CNC along the sixth
      aortic arch. The ductus wall, filled with CNC, was intimately associated with the
      recurrent laryngeal nerve, also filled with CNC, thereby strongly suggesting a
      role for CNC in ductal closure.

PMID- 8291693
TI  - Computer analysis of the human embryo growth curve: differences between published
      ultrasound findings on living embryos in utero and data on fixed specimens.
AB  - Accurate information on the normal growth rate of the human embryo is fundamental
      to a better understanding of the embryonic period of pregnancy. Crown-rump length
      measured previously in utero (N = 227) with vaginal ultrasound in 107 in vitro
      fertilization (IVF) or gamete intrafallopian transfer (GIFT) singleton
      pregnancies was compared to the greatest length of fixed human embryos from the
      Carnegie collection, of known developmental stage whose postovulatory ages were
      estimated from menstrual histories. Average crown-rump length in utero was 60% of
      the greatest length of the fixed specimens prior to postovulation day 33, but
      were equal after postovulation day 40. The growth rate of in utero embryos and
      fixed specimens, analyzed by computer using exponential equations, was compared
      to linear and polynomial equations used in previously published embryo growth
      tables. The exponential equation, length = exp(a + B/age), fit in utero
      measurements best, while the equation length = exp[a + b/exp(age)] fit the fixed
      specimens best. Differences between length in utero and in fixed specimens may be
      related to distortion of the fixed embryos resulting from the formalin fixation,
      to ultrasound distortion, to curling of the embryo, or to incorrectly estimated
      ages of the fixed specimens. Study of human embryos in utero is now practical
      with vaginal ultrasound.

PMID- 8291694
TI  - Role for differential cell proliferation in perforation and rupture of chick
      pharyngeal closing plates.
AB  - Patterns of cell proliferation show two distinct domains around avian pharyngeal
      closing plates as they form, perforate, and rupture. Pouch endoderm and groove
      ectoderm are in one domain showing 81-86% proliferation, which suggests
      relatively rapid growth. Cells in epithelia that comprise the pharyngeal closing
      plates contiguous with pouch and groove epithelia are vital but are dividing at a
      significantly lower percentage (62-64%). This phenomenon is similar to the lag in
      growth reported for cells in the oral membrane around the time of rupture (Miller
      and Olcott, 1989: Anat. Rec., 223:204-208), is consistent with Waterman's
      suggestion (1985: Anat. Rec., 211:450-457) that cellular reorganization, rather
      than massive degeneration, is a major mechanism of initial perforation, and
      suggests that differential growth is a contributor to performation and rupture of
      chick pharyngeal closing plates.

PMID- 8291695
TI  - Effect of soft diet and aging on rat masseter muscle and its motoneuron.
AB  - To determine the effect of a soft diet and aging on the masticatory motor unit,
      we investigated the morphologic and metabolic properties of the superficial
      masseter muscle and its motoneurons in rats. Twenty rats were divided into four
      groups of five rats: rats fed a hard diet until 4 months after birth (hard,
      young), rats fed a soft diet until 4 months after birth (soft, young), rats fed a
      hard diet until 22 months after birth (hard, old), and rats fed a soft diet until
      22 months after birth (soft, old). The diameter of the fast-twitch oxidative
      glycolytic muscle fiber was significantly smaller in the soft than the hard, and
      in the old than the young groups. The glycolytic enzyme (phosphofructokinase)
      activity of the muscle was significantly weaker in the old than the young group.
      There was no significant difference in soma diameter of the motoneurons between
      the soft and hard group, while the diameter was significantly larger in the old
      than in the young group. There was no significant difference in NADH-diaphorase
      activity of the motoneurons between the soft and hard group, while significantly
      less activity was demonstrated in the old than in the young group. The reduction
      in motor unit activity caused by the soft diet is considered to influence the
      morphologic and metabolic properties in the superficial masseter muscle but not
      in its motoneurons. The reduction in the oxidative enzyme activity of motoneurons
      with aging may occur regardless of the reduction in motor unit activity.

PMID- 8291696
TI  - Cytologic structures unique to Deiters cells of the cochlea.
AB  - Deiters cells in the gerbil cochlea disclosed unusual ultrastructural features. A
      sharp transition zone separated the cell body underlying outer hair cells into an
      upper compartment with numerous organelles and a lower part devoid of structures
      other than the microtubule stalk. Deiters cells exhibited a unique structure, the
      rosette complex, which consisted of a core of densely fibrillar trabeculae,
      enclosed in a filamentous meshwork and surrounded by tubulocisternal endoplasmic
      reticulum. The dense trabeculae radiated in columns downward from an apical
      translucent area toward a lucent zone around the nucleus. They also spread to the
      medial plasmalemma enveloping nerves and upward into the base of the phalanx.
      Frequent, small Golgi complexes bordered the tubular reticulum. The distinctive
      mitochondria of Deiters cells frequently paralleled the plasmalemma, revealed an
      elongated, often arched profile, and contained sparse, longitudinally aligned
      cristae. The stalk, composed of characteristic microtubule bundles resembling
      those in pillar cells, ascended from basal to apical plasmalemma of the cell body
      and into the phalanx and reticular lamina as previously described. The stalk
      appeared also to ramify into smaller microtubule bundles in apical cytosol
      penetrating the rosette complex. Nuclei in Deiters cells differed from those in
      hair cells in their location high in the cell and in showing chromatin dispersion
      indicative of more active protein synthesis.

PMID- 8291697
TI  - Gross anatomy: an outdated subject or an essential part of a modern medical
      curriculum? Results of a questionnaire circulated to final-year medical students.
AB  - Final-year undergraduate medical students were given a questionnaire on the gross
      anatomy curriculum they had experienced in their first year at medical school 5
      years earlier. They were asked to evaluate the relevance of the dissection
      course, lectures and seminars in gross anatomy for clinical courses, clerkships,
      and everyday practical work on the ward. About two-thirds of the students found
      the time spent on 10 different regions in anatomy to be adequate, and a
      considerable number of students would have liked even more details. The vast
      majority expressed a wish to repeat topographical anatomy during their clinical
      teaching. Furthermore, approximately 75% of the students showed interest in
      short, specialized dissection courses during the clinical curriculum. Medical
      students just before graduation ranked gross anatomy with the dissection course
      and integrated clinical topics as a keystone for their clinical courses. The
      results of such surveys should be taken into consideration when discussing
      modifications to teaching gross anatomy or arguing about a balanced dissection
      course.

PMID- 8291698
TI  - The name cranial ovarian suspensory ligaments in mammalian anatomy should be used
      only to indicate the structures derived from the foetal cranial mesonephric and
      gonadal ligaments.
AB  - The term ovarian suspensory ligament appears ambiguous when human adult anatomy
      textbooks are compared with human embryology or with general mammalian anatomy
      textbooks. The term ovarian suspensory ligament in laboratory rodents and
      domestic animals indicates homologous structures during foetal (the cranial
      mesonephric and gonadal ligaments) and later life (the cranial mesonephric
      ligament derivatives). In human foetal anatomy textbooks ovarian suspensory
      ligament is generally applied to this same ligament. However, in human adult
      anatomy textbooks ovarian suspensory ligament is widely applied to the part of
      the (uterine) broad ligament which contains the uterine and ovarian blood and
      lymphatic vessels and nerves. This inconsistency in human anatomy books raises
      confusion on the nature of the foetal and adult ovarian suspensory ligaments and
      inconsistencies in the description of the normal anatomical relationships of the
      ovaries between humans and other mammals. For the proper understanding of normal
      gonadal growth and development within the abdomen, it is important to maintain a
      consistent nomenclature of the cranial ovarian structures. The current practice
      in veterinary and other mammalian textbooks offers a solid point of departure.

PMID- 8291699
TI  - The pharmacokinetics of propofol in children using three different data analysis
      approaches.
AB  - BACKGROUND: Accurate dosing of propofol in children requires accurate knowledge
      of propofol pharmacokinetics in this population. Improvement in pharmacokinetic
      accuracy may depend on the incorporation of individual patient factors into the
      pharmacokinetic model or the use of population approaches to estimating the
      pharmacokinetic parameters. We investigated whether incorporating individual
      subject covariates (e.g., age, weight, and gender) into the pharmacokinetic model
      improved the accuracy. We also investigated whether the use of a mixed-effects
      population model (e.g., the computer program NONMEM) improved the accuracy of the
      pharmacokinetic model beyond the accuracy obtained with models estimated using
      two simple approaches. METHODS: We studied 53 healthy, unpremedicated children
      (28 boys and 25 girls) ranging from 3 to 11 yr of age. Twenty children only
      received an initial loading dose of 3 mg/kg intravenous propofol. In the
      remaining 33 children, an initial intravenous propofol dose of 3.5 mg/kg was
      followed by a propofol maintenance infusion. Six hundred fifty-eight venous
      plasma samples were gathered and assayed for propofol concentrations. Three
      different regression techniques were used to analyze the pharmacokinetics: the
      "standard two-stage" approach, the "naive pooled-data" approach, and the
      nonlinear mixed-effects modeling approach (as implemented in NONMEM). In both the
      pooled-data and mixed-effects approaches, individual covariates (age, weight,
      height, body surface area, and gender) were added to the model to examine whether
      they improved the quality of the fit. Accuracy of the model was measured by the
      ability of the model to describe the observed concentrations. RESULTS: The
      pharmacokinetics of propofol in children were best described by a three
      compartment pharmacokinetic model. There were no appreciable differences among
      the pharmacokinetics estimated using the two-stage, pooled-data, and mixed
      effects approaches. Weight was a significant covariate, and the weight
      proportional model was supported by all three regression approaches. The
      pharmacokinetic parameters of the weight-proportional pharmacokinetic model
      (pooled-data approach) were: central compartment (V1) = 0.52 1 x kg-1; rapid
      distribution compartment (V2) = 1.01 x kg-1; slow-distribution compartment (V3) =
      8.2 1 x kg-1; metabolic clearance (Cl1) = 34 ml.kg-1 x min-1; rapid-distribution
      clearance (Cl2) = 58 ml.kg-1 x min-1; and slow-distribution clearance (Cl3) = 26
      ml.kg-1 x min-1. The inclusion of age as an additional covariate of V2
      statistically improved the model, but the actual improvement in the fit was
      small. CONCLUSIONS: The pharmacokinetics of propofol in children are well
      described by a standard three-compartment pharmacokinetic model. Weight-adjusting
      the volumes and clearances significantly improved the accuracy of the
      pharmacokinetics. Adjusting the pharmacokinetics for inclusion of additional
      patient covariates or using a mixed-effects model did not further improve the
      ability of the pharmacokinetic parameters to describe the observations.

PMID- 8291700
TI  - Nifedipine and intraoperative core body temperature in humans.
AB  - BACKGROUND: Initial anesthetic-induced hypothermia results largely from core-to
      peripheral redistribution of heat. Nifedipine administration may minimize
      hypothermia by inducing vasodilation well before induction of anesthesia.
      Although vasodilation would redistribute heat to peripheral tissues,
      thermoregulatory responses would maintain core temperature. After equilibration,
      the patient would be left vasodilated, with a small core-to-peripheral
      temperature gradient. Minimal redistribution hypothermia may accompany subsequent
      induction of anesthesia, because heat flow requires a temperature gradient. In
      contrast, similar vasodilation concurrent with anesthetic-induced vasodilation
      may augment redistribution hypothermia. Accordingly, the authors tested the
      hypothesis that nifedipine treatment for 12 h before surgery would minimize
      intraoperative redistribution hypothermia, whereas nifedipine treatment
      immediately before induction of anesthesia would aggravate hypothermia. METHODS:
      Patients undergoing hip arthroplasty were randomly assigned to: (1) 20 mg long
      acting nifedipine orally 12 h before surgery, and 10 mg sublingually 1.5 h before
      surgery (n = 10); (2) nifedipine 10 mg sublingually just before induction of
      anesthesia (n = 10); and (3) no nifedipine (control, n = 10). Anesthesia was
      maintained with isoflurane and 60% nitrous oxide. Administered intravenous fluids
      were heated, but the patients were not otherwise actively warmed. RESULTS: Core
      temperature decreased 0.8 degree C in the first hour of surgery in the patients
      given nifedipine the night before and the morning of surgery, which was
      significantly less than in the control group (1.7 degree C in the first hour). In
      contrast, core temperature decreased 2.0 degrees C in the first hour of surgery
      in the patients given nifedipine immediately before induction of anesthesia.
      During the subsequent 70-130 min of anesthesia, core temperature decreased at
      roughly comparable rates in each group. After 130 min of anesthesia, core
      temperature in the two nifedipine-treated groups differed by 1.6 degrees C, and
      the temperatures in all three groups differed significantly. CONCLUSIONS:
      Vasodilation induced by nifedipine well before induction of anesthesia minimized
      redistribution hypothermia, presumably by decreasing the core-to-peripheral
      tissue temperature gradient. In contrast, redistribution hypothermia was
      aggravated by administration of the same drug immediately before induction of
      anesthesia. Drug-induced modulation of vascular tone thus produces clinically
      important alterations in intraoperative core temperature.

PMID- 8291701
TI  - Carbon dioxide absorption is not linearly related to intraperitoneal carbon
      dioxide insufflation pressure in pigs.
AB  - BACKGROUND: Carbon dioxide absorption into the blood during laparoscopic surgery
      using intraperitoneal carbon dioxide insufflation may lead to respiratory
      acidosis, increased ventilation requirements, and possible serious cardiovascular
      compromise. The relationship between increased carbon dioxide excretion (VCO2)
      and intraperitoneal carbon dioxide insufflation pressure has not been well
      defined. METHODS: In 12 anesthesized pigs instrumented for laparoscopic surgery,
      intraperitoneal carbon dioxide (n = 6) or helium (n = 6) insufflation pressure
      was increased in steps, and VCO2 (metabolic cart), dead space, and hemodynamics
      were measured during constant minute ventilation. RESULTS: VCO2 increases rapidly
      as intraperitoneal insufflation pressure increases from 0 to 10 mmHg; but from 10
      to 25 mmHg, VCO2 does not increase much further. PaCO2 increases continuously as
      intraperitoneal insufflation pressure increases from 0 to 25 mmHg. Hemodynamic
      parameters remained stable. CONCLUSIONS: By considering Fick's law of diffusion,
      the initial increase in VCO2 is likely accounted for by increasing peritoneal
      surface area exposed during insufflation. The continued increase in PaCO2 without
      a corresponding increase in VCO2 is accounted for by increasing respiratory dead
      space.

PMID- 8291702
TI  - Regulation of inspiratory neuromuscular output during synchronized intermittent
      mechanical ventilation.
AB  - BACKGROUND: In synchronized intermittent mandatory ventilation, it is generally
      accepted that the work of the inspiratory muscles is decreased by the ventilator
      so that their activity can be modulated by the frequency of assisted breaths. We
      examined the validity of this concept, which recently has been questioned.
      METHODS: We studied five patients receiving synchronized intermittent mandatory
      ventilation because of an acute exacerbation of chronic obstructive pulmonary
      disease. The level of machine assistance, defined as the percentage of total
      ventilation delivered by the ventilator, was varied from a high (> 60%) to a
      medium (20-50%) and to the lowest tolerated value (0% in four patients).
      Esophageal pressure, air flow, and the electromyograms of the diaphragm and
      sternocleidomastoid muscles were recorded. At each level of machine assistance,
      distinguishing assisted from spontaneous breaths, the duration of electrical
      activation, the integrated electromyograms, and the work of breathing were
      computed. RESULTS: The durations of electrical activation and the integrated
      electromyograms of the diaphragm and sternocleidomastoid were similar in
      successive spontaneous and assisted breaths. At > 60% of machine assistance, the
      cumulative values per minute of the integrated electromyograms of the diaphragm
      and sternocleidomastoid and the work of breathing were reduced only by 38, 32,
      and 44%, respectively, compared with the lowest tolerated level of machine
      assistance. The durations of electrical activation did not change with increasing
      level of machine assistance. CONCLUSIONS: The degree of inspiratory muscle rest
      achieved by synchronized intermittent mandatory ventilation is not proportional
      to the level of machine assistance; furthermore, the inspiratory motor output is
      not regulated breath by breath but rather is constant for a given level of
      machine assistance.

PMID- 8291703
TI  - Synergistic antinociceptive interaction after epidural coadministration of
      morphine and lidocaine in rats.
AB  - BACKGROUND: Clinically, epidural coadministration of opioids and local
      anesthetics has provided excellent analgesia for various types of pain. However,
      information about the interaction of these drugs when administered epidurally is
      limited. Therefore, we evaluated the antinociceptive interaction between morphine
      and lidocaine on both somatic and visceral noxious stimuli in the rat. METHODS:
      Male Sprague-Dawley rats weighing 300-350 g had epidural catheters implanted at
      T13-L1. Every rat was tested with both the tail flick test, a somatic noxious
      stimulus, and the colorectal distension test, a visceral noxious stimulus. In the
      colorectal distension test, the response threshold was defined by the pressure
      within the intracolonic balloon required to trigger abdominal contraction. Tail
      flick latency and colorectal distension threshold were measured before and for
      180 min after the administration of morphine, lidocaine, or combinations of those
      drugs. To characterize the interaction, isobolographic analysis was performed
      with a fixed morphine: lidocaine dose ratio of 1:1,000. RESULTS: Epidural
      morphine (0.1-10 micrograms) and lidocaine (100-800 micrograms) increased the
      tail flick latency and colorectal distension threshold in a dose- and time
      dependent fashion. The epidural injection of morphine (0.1-1 microgram) mixed
      with lidocaine (100 or 200 micrograms) significantly increased the peak effect
      and prolonged the duration of effects compared with each drug alone in both
      nociceptive tests. Areas under the curves, calculated to express overall
      magnitude and duration of antinociceptive effects, were significantly increased
      by combinations as compared with each drug alone, especially with morphine 0.1
      microgram and lidocaine 100 or 200 micrograms, each of which alone produced no
      change in the area under the curve. Isobolographic analysis revealed that
      epidural morphine and lidocaine interact synergistically at 10, 20, and 30 min
      after injection in both somatic and visceral nociception tests. Both potency
      ratio analysis and fractional analysis confirmed the finding of the
      isobolographic analysis. Epidural naloxone antagonized the antinociceptive
      effects produced by the combination. CONCLUSION: These data demonstrate that
      epidurally coadministered morphine and lidocaine produce synergistic analgesia
      and prolong the duration of analgesia in tests of somatic and of visceral
      nociception.

PMID- 8291704
TI  - Effects of pentobarbital on incorporation of plasma palmitate into rat brain.
AB  - BACKGROUND: Barbiturates are reported to reduce brain oxidative metabolism and
      brain free fatty acid release during ischemia by mechanisms that are as yet
      unclear. To elucidate their action on brain lipid metabolism, an in vivo method
      was used to quantify the effect of pentobarbital on the incorporation of
      radiolabeled palmitic acid from blood into lipids of the rat brain. METHODS:
      [9,10(-3)H]-Palmitate was infused intravenously in an awake rat or in a rat
      lightly anesthetized or made comatose by pentobarbital. Twenty minutes after
      infusion was begun, the rat was killed and non-3H2O radioactivity in individual
      brain lipid compartments was determined. Incorporation coefficients (k*) were
      calculated by dividing the lipid compartment radioactivities by the integrated
      plasma radioactivity to 20 min. RESULTS: Net brain k* for [9,10(-3)H]-palmitate
      was reduced by 36-40% in pentobarbital-anesthetized rats. This reduction was
      unrelated to depth of anesthesia or to the presence of hypercapnia and acidosis,
      because breathing 7.5% CO2 had no effect on k* in awake rats. Anesthesia reduced
      radiolabel incorporation into phospholipids by 46-53% and into neutral lipids by
      20-26% but did not change the distribution of radiolabel among phospholipid or
      neutral lipid classes. CONCLUSIONS: Pentobarbital has a profound effect on brain
      lipid metabolism. It reduces incorporation of plasma palmitate into brain, more
      so into phospholipids than into neutral lipids, independently of changes in
      cerebral blood flow. Reduced incorporation likely reflects reduced turnover of
      palmitate within brain lipids (mainly phosphatidylcholine), consistent with
      evidence that barbiturates also reduce release of free fatty acids during brain
      ischemia.

PMID- 8291705
TI  - The effect of adenosine-induced hypotension on systemic and splanchnic
      hemodynamics during halothane or sevoflurane anesthesia in the rat.
AB  - BACKGROUND: It has been suggested that the liver may be at risk for ischemic
      damage during adenosine-induced hypotension. This notion, however, is somewhat
      inconsistent with the understanding that adenosine is a powerful vasodilator of
      the splanchnic circulation. To help clarify the effect of adenosine-induced
      hypotension on splanchnic hemodynamics, we studied the systemic and splanchnic
      hemodynamic responses to adenosine, both alone and in the presence of halothane
      or sevoflurane. METHODS: Systemic and splanchnic hemodynamics were determined
      during the infusion of adenosine in 36 rats allocated randomly to one of three
      study groups: (1) awake, (2) halothane anesthesia (1.0 MAC), or (3) sevoflurane
      anesthesia (1.0 MAC). Adenosine was infused at a rate sufficient to decrease the
      mean arterial pressure by 35-38% from awake control values. Cardiac output and
      organ blood flows were measured using the radiolabeled microsphere technique.
      RESULTS: Adenosine infusion produced stable hypotension of rapid onset due to a
      reduction in systemic vascular resistance. Stroke volume increased, but cardiac
      output remained unchanged in the awake and sevoflurane groups because of a
      decrease in heart rate. Infusion of adenosine during halothane anesthesia
      increased cardiac output enough to compensate for the decrease in cardiac output
      due to halothane alone. In the splanchnic circulation, there was an increase in
      portal tributary (42%, P < 0.01) and hepatic arterial (38%, P < 0.05) blood flows
      during adenosine infusion in awake rats. This resulted in an overall increase in
      total liver blood flow (42%, P < 0.01). Halothane anesthesia was associated with
      a decrease in portal tributary blood flow (28%, P < 0.05). In contrast,
      sevoflurane anesthesia was associated with an increase in hepatic arterial flow
      (35%, P < 0.05) but with no change in portal tributary blood flow. During
      halothane anesthesia, adenosine infusion increased portal tributary (90%, P <
      0.01) and hepatic arterial (37%, P < 0.05) blood flows, thereby increasing total
      liver blood flow to values similar to those in awake adenosine-infused rats.
      During sevoflurane anesthesia, adenosine infusion increased portal tributary
      blood flow (48%, P < 0.01), but hepatic arterial blood flow did not increase
      beyond the values observed during sevoflurane anesthesia alone. CONCLUSIONS:
      These findings demonstrate that adenosine is a potent vasodilator of portal
      tributary and hepatic arterial vasculature in the rat and that the splanchnic
      hemodynamic effects of adenosine predominate over those of halothane and
      sevoflurane.

PMID- 8291706
TI  - Plasma, brain, and spinal cord concentrations of thiopental associated with
      hyperalgesia in the rat.
AB  - BACKGROUND: Although low doses of barbiturates are widely believed to increase
      sensitivity to pain, studies of the electrophysiologic effects of these drugs on
      the neurons involved in nociception in the spinal cord have detected only
      depressant effects. The goal of the studies reported here was to quantify the
      hyperalgesia resulting from low-dose thiopental infusions and to measure the
      associated concentrations of thiopental in the plasma, brain, and spinal cord.
      METHODS: Nociception was measured using the threshold for motor response to
      pressure stimulation of the tail (nociceptive threshold) and tail flick latency
      in the rat. Thiopental was administered by intravenous infusions designed to
      produce plasma concentrations that either slowly increased or remained at a
      steady state. Plasma and tissue thiopental concentrations were measured by high
      performance liquid chromatography. RESULTS: We observed a reduction in
      nociceptive threshold that was correlated with the plasma thiopental
      concentration over the range 2-20 micrograms.ml-1 (7.6-76 microM). The
      relationship was nonlinear. Nociceptive threshold reached a nadir (36% less than
      control values) at a mean plasma thiopental concentration of 13.7 micrograms.ml-1
      (51.9 microM). The steady-state study showed a similar reduction in nociceptive
      threshold, with an equilibrium plasma thiopental concentration of 7.6 +/- 1.3
      micrograms.ml-1 (28.8 +/- 4.9 microM). Concentrations of thiopental in brain and
      spinal cord samples were 1.7 +/- 0.03 and 3.5 +/- 1.7 micrograms.g-1,
      respectively. CONCLUSIONS: These studies confirm previous reports of hyperalgesia
      in association with small doses of thiopental. Reductions in nociceptive
      threshold and tail flick latency were observed in association with spinal cord
      concentrations of thiopental in a range reported by others to depress the
      electrophysiologic activity of neurons involved in nociception.

PMID- 8291707
TI  - Effects of hypothermia or anesthetics on hippocampal glutamate and glycine
      concentrations after repeated transient global cerebral ischemia.
AB  - BACKGROUND: The search for cerebroprotective pharmacologic interventions has been
      based on the assumption that reducing the cerebral metabolic rate may enhance the
      cerebral tolerance for ischemic episodes. Recently, evidence has accumulated
      implicating excitatory amino acids (e.g., glutamate) as mediators of ischemic
      brain injury. We investigated the effects of mild hypothermia (32 degrees C),
      pentobarbital, isoflurane, and propofol on hippocampal extracellular
      concentrations of glutamate and glycine after repeated global ischemia. METHODS:
      New Zealand white rabbits were initially anesthetized with halothane in oxygen.
      Brain epidural temperature was reduced by external cooling in the hypothermia
      group to 32 degrees C (n = 5). A burst-suppressed electroencephalogram pattern
      was achieved in the other groups with isoflurane (n = 7), pentobarbital (n = 6),
      or propofol (n = 6). Halothane-anesthetized rabbits (1% inspired) served as the
      control group (n = 5). In all groups, two global cerebral ischemic episodes (each
      7.5 min) were produced by a combination of neck tour niquet inflation and
      induction of systemic hypotension. Periischemic hippocampal glutamate and glycine
      concentrations were estimated using in vivo microdialysis and high-performance
      liquid chromatography (two-way analysis of variance, P < 0.05). RESULTS:
      Glutamate concentrations were similar in the five groups during the baseline
      period. Hypothermia (32 degrees C) was associated with significantly lower
      concentrations of glutamate during both the first and second ischemic periods
      when compared with all other groups. Although there were no differences in
      glycine concentrations among groups during the first ischemic episode, glycine
      concentrations were significantly lower in the hypothermic group compared with
      the control, isoflurane, and pentobarbital groups during the second episode of
      cerebral ischemia. Glycine concentrations also were lower in the propofol group
      when compared to the isoflurane and pentobarbital groups. CONCLUSION: Hypothermia
      (32 degrees C) attenuates ischemia-induced increases in both glutamate and
      glycine concentrations after repeated global cerebral ischemia. Propofol
      attenuated glycine increases in a manner similar to that of hypothermia but did
      not attenuate ischemia-induced glutamate increases. There were no differences in
      hippocampal glutamate or glycine concentrations for animals receiving isoflurane,
      halothane, or pentobarbital.

PMID- 8291708
TI  - AIDS and the central nervous system. Implications for the anesthesiologist.

PMID- 8291709
TI  - Propofol in pediatrics. Lessons in pharmacokinetic modeling.

PMID- 8291710
TI  - A simplified gas chromatographic method for quantifying the sevoflurane
      metabolite hexafluoroisopropanol.
AB  - BACKGROUND: The results of sevoflurane biotransformation (fluoromethyl
      1,1,1,3,3,3,-hexafluoro-2-propyl ether) to inorganic fluoride have been examined.
      However, these investigations have lacked a simplified assay for determining the
      primary organic metabolite, hexafluoroisopropanol. Previous attempts have
      involved extensive extraction steps, complicated derivatization techniques, or
      sophisticated detectors. METHODS: After enzymatic hydrolysis of conjugates,
      hexafluoroisopropanol is detected readily using a head space gas chromatographic
      analysis with a flame ionization detector. RESULTS: The gas chromatographic
      technique was linear from 10 to 800 microM with a correlation coefficient of
      0.999. The detection limit was 10 microM in urine and 25 microM in blood.
      CONCLUSIONS: This simplified approach does not require the extraction,
      derivatization, or mass spectrometric detectors of previous methods. As
      sevoflurane utilization and research increases, this assay should allow for a
      variety of laboratory and clinical disposition studies to be performed.

PMID- 8291711
TI  - The anesthetic implications of a patient with Farber's lipogranulomatosis.

PMID- 8291712
TI  - Normal lactate/pyruvate ratio during overwhelming polymicrobial bacteremia and
      multiple organ failure.

PMID- 8291713
TI  - Postanesthetic apnea in full-term infants after pyloromyotomy.

PMID- 8291714
TI  - Electrical safety revisited: a new wrinkle.

PMID- 8291715
TI  - Anemia and hypotension as contributors to perioperative loss of vision.

PMID- 8291716
TI  - Threatening spinal cord compression during anesthesia in a child with
      mucopolysaccharidosis VI.

PMID- 8291717
TI  - Postthyroidectomy laryngoscopic examination.

PMID- 8291718
TI  - Carotid artery-internal jugular fistula: another complication following pulmonary
      artery catheterization via the internal jugular venous route.

PMID- 8291719
TI  - An unusual cause of electrocardiogram "pacemaker artifact": faulty electrical
      grounding of equipment.

PMID- 8291720
TI  - Does flumazenil antagonize midazolam-induced depression of ventilatory response
      to hypoxia?

PMID- 8291721
TI  - Inability to deflate the distal cuff of the laser-flex tracheal tube preventing
      extubation after laser surgery of the larynx.

PMID- 8291722
TI  - Abortion does not lead to euthanasia.

PMID- 8291723
TI  - Costs of administering desflurane or isoflurane via a closed circuit.

PMID- 8291724
TI  - Revised label regarding use of succinylcholine in children and adolescents.

PMID- 8291725
TI  - Revised label regarding use of succinylcholine in children and adolescents.

PMID- 8291726
TI  - Nitrous oxide in early labor. Safety and analgesic efficacy assessed by a double
      blind, placebo-controlled study.
AB  - BACKGROUND: Intermittent self-administered nitrous oxide has long had widespread
      use as an analgesic in labor, but its efficacy has not been adequately
      established. Questions about its effect on maternal oxygenation between labor
      contractions also have been raised. METHODS: Twenty-six women were recruited to
      participate in a randomized, double-blind, cross-over, placebo-controlled study
      to assess the effect of intermittent nitrous oxide inhalation on labor pain and
      maternal hemoglobin oxygen saturation (SPO2) during the first stage of labor.
      Visual analog scale pain scores for each of five consecutive labor contractions
      were measured after administration of either nitrous oxide or compressed air.
      RESULTS: Mean visual analog scale pain scores for five contractions were 5.1,
      5.2, 5.7, 5.2, and 5.6 (nitrous oxide) and 4.9, 5.2, 6.1, 5.6, and 5.7
      (compressed air). There were no statistically significant differences in pain
      when nitrous oxide as compared with compressed air was administered. Pain scores
      did not differ significantly over time as a function of inhaled substance (F =
      0.41, P = 0.53). The mean lowest SPO2 observed between these contractions after
      self-administration of nitrous oxide and air were 97, 97, 97, 97, and 97%
      (nitrous oxide) and 97, 96, 96, 96, and 96% (compressed air). SPO2 was
      significantly higher after nitrous oxide administration (F = 8.8, P = 0.007).
      CONCLUSION: While intermittent self-administered 50% nitrous oxide in oxygen does
      not appear to predispose parturient women to hemoglobin oxygen desaturation, its
      analgesic effect has yet to be clearly demonstrated.

PMID- 8291727
TI  - Relative potency of eltanolone, propofol, and thiopental for induction of
      anesthesia.
AB  - BACKGROUND: The primary purpose of this investigation was to determine the
      relative potency of eltanolone, a new steroid hypnotic, and propofol and
      thiopental when used for induction of general anesthesia. In addition, the
      induction characteristics of propofol and eltanolone were compared. METHODS: One
      hundred seventy-five patients, premedicated with lorazepam 1 mg orally, randomly
      received one of six different doses of either eltanolone or propofol. The
      probability of successful induction (defined as not responsive to verbal commands
      within 2 min) was related to the logarithm of the dose for each drug by means of
      logistic regression analysis. Estimates of ED50 and ED95 for each drug were
      obtained. The incidence of side effects was compared for eltanolone and propofol.
      The potency of thiopental was determined in a parallel study, using an identical
      methodology in 105 patients receiving one of seven different doses of the
      barbiturate. RESULTS: The relative potency of eltanolone was 3.2 times (95%
      confidence interval 2.7-3.8) greater than propofol and 6.0 times (5.3-6.9)
      greater than thiopental. ED50 and ED95 values for eltanolone were 0.46 (0.40
      0.52) and 0.82 (0.68-1.28) mg.kg-1, respectively. Compared to propofol, induction
      of anesthesia with eltanolone is characterized by a lower incidence of injection
      pain (3.5% vs. 58%) and apnea (1.2% vs. 11.2%). CONCLUSIONS: Eltanolone appeared
      to be an effective induction agent that is 3.2 times more potent than propofol
      and 6 times more potent than thiopental. Its use was associated with less pain on
      injection than was propofol.

PMID- 8291728
TI  - Efficacy of the self-inflating bulb in detecting esophageal intubation. Does the
      presence of a nasogastric tube or cuff deflation make a difference?
AB  - BACKGROUND: The principle underlying the use of the self-inflating bulb in
      differentiating esophageal from tracheal intubation is that the trachea is held
      open by rigid cartilaginous rings, whereas the esophagus collapses when a
      negative pressure is applied to its lumen. This investigation was designed to
      test the efficacy of the bulb in detecting esophageal intubation in the presence
      of a nasogastric tube and after tracheal tube cuff deflation. METHODS: In
      anesthetized patients, the trachea and esophagus were intubated with identical
      tubes. The efficacy of the bulb was tested after a nasogastric tube was placed
      (group 1, n = 70) and after cuff deflation (group 2, n = 60) by a second
      anesthesiologist. RESULTS: In patients with nasogastric tubes (group 1), the
      anesthesiologists reported no reinflation of the compressed bulbs connected to
      tubes placed in the esophagus and immediate reinflation when connected to
      tracheally placed tubes in every case. In group 2, the determination of tube
      placement was correct in every case after cuff deflation. Mean (+/- SEM) negative
      pressures generated when compressed bulbs were connected to esophageally placed
      tubes were 57.8 +/- 0.48 mmHg (group 1) and 55.3 +/- 0.52 mmHg (group 2) and
      remained unchanged after the introduction of nasogastric tubes or after cuff
      deflation. CONCLUSIONS: These results confirm that a nasogastric tube or cuff
      deflation does not interfere with the reliability of the self-inflating bulb in
      detecting esophageal intubation and thus does not contribute to false positive
      results. Confirmation of tracheal tube placement by this simple method makes it
      ideal for use with other recognized methods both in and outside the operating
      rooms and enables physicians and emergency personnel to proceed with other
      resuscitative measures.

PMID- 8291729
TI  - The effect of epidural versus general anesthesia on postoperative pain and
      analgesic requirements in patients undergoing radical prostatectomy.
AB  - BACKGROUND: Although preemptive analgesia has been shown to decrease postinjury
      pain in animals, studies in humans have provided controversial results. The
      authors studied whether surgical epidural anesthesia with local anesthetics could
      affect postoperative pain and analgesic demands, when compared with general
      anesthesia. METHODS: Male patients scheduled for radical retropubic prostatectomy
      were randomly assigned to receive epidural anesthesia only (EA, n = 34), combined
      epidural and general anesthesia (EG, n = 32), or general anesthesia only (GA, n =
      30). A lumbar epidural catheter was inserted and tested in all patients. In the
      EA group, an induction dose of 0.25 ml/kg epidural bupivacaine (0.5%) was
      followed during surgery by a continuous infusion of 0.1 ml.kg-1.h-1 0.125%
      bupivacaine. In the EG group, 0.2 ml/kg epidural bupivacaine (0.5%) was injected
      after induction of general anesthesia but before surgery, followed by epidural
      infusion of 0.1 ml.kg-1.h-1 0.125% bupivacaine. In the GA group, anesthesia was
      maintained with morphine, isoflurane, and N2O. Epidural patient-controlled
      analgesia (PCA) was provided with bupivacaine and fentanyl for all patients in
      the postoperative period. Postoperative pain scores and analgesic requirements
      were examined and compared between groups every 4-8 h for 3-5 postoperative days.
      RESULTS: Intraoperatively, EA patients received significantly more epidural
      bupivacaine than EG patients (129 +/- 6 mg vs. 98 +/- 6 mg, respectively.
      Recovery room median residual sensory level in EA patients (T6 +/- 2) was
      significantly higher than in EG patients (T10 +/- 2). PCA demand was greater in
      the GA and EG groups when compared with the EA group in postoperative days 2 (126
      +/- 9 ml, 112 +/- 9 ml, 90 +/- 6 ml, respectively; P = 0.01) and 3 (89 +/- 10 ml,
      83 +/- 9 ml, 48 +/- 5 respectively; P = 0.005). There was no difference in PCA
      demand between the GA and EG groups in the postoperative period. No significant
      clinical differences in postoperative mean pain scores were recorded in the first
      5 days after surgery in the three anesthetic groups (range 0-2/10). CONCLUSIONS:
      In patients undergoing lower abdominal surgery, the neuraxial blockade and
      surgical anesthesia achieved by epidural local anesthetics was associated with
      decreased postoperative analgesic demands. Lower postoperative analgesic
      requirements in the EA group, when compared with both the EG and GA groups,
      indicate that: (1) EA patients had less postoperative pain, and (2) an efficient
      intraoperative blockade of noxious afferent signals to the central nervous system
      is fundamental in reducing postoperative pain.

PMID- 8291730
TI  - Inhaled nitric oxide selectively decreases pulmonary vascular resistance without
      impairing oxygenation during one-lung ventilation in patients undergoing cardiac
      surgery.
AB  - BACKGROUND: Inhaled nitric oxide (NO), an endothelium-derived relaxing factor, is
      a selective pulmonary vasodilator. The authors investigated whether inhaled NO
      decreases pulmonary vascular resistance (PVR) while preserving hypoxic pulmonary
      vasoconstriction and whether it maintains or improves oxygenation in patients
      during one-lung ventilation. METHODS: In supine cardiac surgical patients with a
      normal mean pulmonary artery pressure (PAP) (< 25 mmHg, n = 10) or a moderately
      elevated PAP (25-35 mmHg, n = 10), one-lung ventilation was established with 80%
      oxygen and 20% nitrogen followed by the same gas mixture containing 20 ppm NO for
      6 min. RESULTS: Inhaled NO decreased (P < 0.05) PAP from 30 +/- 2 to 27 +/- 2
      mmHg in the patients with moderate pulmonary hypertension. Likewise, PVR
      decreased (P < 0.05) from 266 +/- 10 to 205 +/- 8 dyn.s.cm-5. The PAP and PVR did
      not change significantly after NO inhalation in the patients without pulmonary
      hypertension. All other hemodynamic variables remained unchanged after inhalation
      of NO in both groups. In the patients with pulmonary hypertension, the PAP and
      PVR returned to baseline after discontinuation of inhaled NO. Inhaled NO did not
      significantly change the arterial oxygen tension or venous admixture in either
      group of patients. Ventilation, airway pressure, tidal volume, and lung
      compliance also were unaffected by inhaled NO. CONCLUSIONS: This study
      demonstrates that 20 ppm inhaled NO is a selective pulmonary vasodilator in
      patients with moderate pulmonary hypertension secondary to cardiac disease who
      are undergoing one-lung ventilation. In contrast to what would be expected with
      intravenous vasodilators that inhibit hypoxic pulmonary vasoconstriction, inhaled
      NO does not increase the venous admixture or impair oxygenation.

PMID- 8291731
TI  - Use of ketorolac after lower abdominal surgery. Effect on analgesic requirement
      and surgical outcome.
AB  - BACKGROUND: Ketorolac is a nonsteroidal antiinflammatory agent with opioid
      sparing properties. The effect of ketorolac on postoperative opioid analgesic
      requirement and surgical outcome was evaluated in 198 women after abdominal
      hysterectomy procedures using a double-blind protocol design. METHODS: Patients
      were randomly assigned to receive either 60 mg intravenous (2 ml) ketorolac,
      followed by 30 mg intravenously (in saline 20 ml) over 30 min every 6 h, or 2 ml
      intravenous saline, followed by saline 20 ml intravenously over 30 min every 6 h,
      for up to 72 h. The postoperative opioid analgesic requirement was assessed using
      a patient-controlled analgesia (PCA) device to self administer either morphine or
      meperidine. The authors also evaluated pain, sedation (or drowsiness), fatigue,
      quality of sleep, and postoperative side effects at 2-8-h intervals for up to 72
      h after surgery. RESULTS: Ketorolac decreased the PCA opioid usage on the night
      of operation and during the first postoperative day. Ketorolac also improved the
      quality of sleep during the first night after surgery. Although ketorolac- (vs.
      saline-) treated patients had a significantly shorter time to passage of bowel
      gas (50 +/- 24 h vs. 61 +/- 25 h), there were no clinically significant
      differences in the times to oral intake, unassisted ambulation, or hospital
      discharge. There were also no differences in the overall incidence of side
      effects in the ketorolac- (vs. saline-) treated patients. However, the use of
      ketorolac with opioid PCA was associated with a reduced need for antiemetic
      therapy on the postsurgical ward. CONCLUSIONS: The authors conclude that the
      opioid-sparing effects of ketorolac contributed few clinically significant
      advantages after abdominal hysterectomy procedures.

PMID- 8291732
TI  - The electrophysiologic effects of volatile anesthetics and sufentanil on the
      normal atrioventricular conduction system and accessory pathways in Wolff
      Parkinson-White syndrome.
AB  - BACKGROUND: The effects of volatile agents and sufentanil anesthesia on the
      electrophysiologic properties of the accessory pathway and on the incidence of
      intraoperative tachyarrhythmias in patients with Wolff-Parkinson-White syndrome
      are unknown. Therefore, we studied these agents for their use in patients
      undergoing ablative procedures or requiring a general anesthetic for other
      surgeries. METHODS: Twenty-one patients with Wolff-Parkinson-White syndrome
      undergoing surgical ablation were anesthetized with sufentanil (20
      micrograms/kg), lorazepam (0.06 mg/kg), and vecuronium (20 mg). After sternotomy,
      the electrophysiologic study during antegrade stimulation consisted of the
      effective refractory period of the right atrium, atrioventricular node, and
      accessory pathway; the shortest cycle length of the atrioventricular node and
      accessory pathway; and the coupling interval. During retrograde stimulation, the
      effective refractory period of the right ventricle and accessory pathway and the
      shortest cycle length of the accessory pathway were measured and compared to
      preoperative electrophysiologic values. Patients then were randomized to receive
      1 MAC of halothane, isoflurane, or enflurane, and the electrophysiologic study
      was repeated. RESULTS: Sufentanil-lorazepam caused mild prolongation (P < 0.05)
      of the effective refractory period of the accessory pathway and the shortest
      cycle length of the atrioventricular node. Enflurane and isoflurane significantly
      prolonged all parameters related to refractoriness during antegrade conduction,
      with enflurane having the largest effect. During retrograde conduction,
      isoflurane prolonged the effective refractory period of the right ventricle and
      accessory pathway and the shortest cycle length of the accessory pathway, whereas
      enflurane prolonged only the accessory pathway effective refractory period and
      shortest cycle length. Halothane had the least effect on refractoriness, causing
      significant prolongation of the atrioventricular node effective refractory period
      and the shortest cycle length of the accessory pathway only during antegrade
      conduction. The coupling interval, a measure of the period of vulnerability to
      supraventricular tachycardia, was prolonged only by halothane and isoflurane.
      Supraventricular tachycardia was still obtainable in all patients. CONCLUSIONS:
      Sufentanil-lorazepam has no clinically significant effect on the
      electrophysiologic expression of the accessory pathway. Of the volatile agents,
      enflurane most, isoflurane next, and halothane least increased refractoriness
      within the accessory and atrioventricular pathways. Therefore, administration of
      these volatile agents during ablative procedures may confound interpretation of
      postablative studies used to determine the success of ablation treatment.
      Conversely, in patients with preexcitation syndrome requiring general anesthesia
      for nonablative procedures, volatile agents may reduce the incidence of
      perioperative tachyarrhythmias because of their effects on refractoriness.
      Enflurane would be the agent of choice because it increases refractoriness the
      most without prolonging the coupling interval.

PMID- 8291734
TI  - An objective methodology for task analysis and workload assessment in anesthesia
      providers.
AB  - BACKGROUND: Administering anesthesia is a complex task in which either human or
      equipment failure can have disastrous consequences. An improved understanding of
      the nature of the anesthesiologist's job could provide a more rational basis for
      improvements in provider training as well as the design of anesthesia equipment.
      The objective of this study was to develop a set of techniques to evaluate
      anesthesiologist performance and to determine what information could be obtained
      from performing real-time task assessment and workload analysis tests in the
      operating room. METHODS: The methodology used included time-motion analysis,
      secondary task probing, and subjective workload assessment. The time-motion data
      was subjected to subsequent analysis to generate quantitative measures such as
      task duration (time spent focused on an individual task) and task density (the
      number of tasks initiated per minute). The latency of response to a "vigilance
      light" was used as a secondary task probe. Finally, both the observer and the
      subjects themselves scored workload at 10-15-min intervals throughout the case.
      Two groups of anesthesia providers performing general endotracheal anesthesia for
      simple ambulatory surgical cases (1-4 h duration) were examined using this
      methodology. In the first group, 3rd-yr anesthesia residents and experienced
      certified registered nurse anesthetists (n = 11) performed cases under limited
      supervision by an attending anesthesiologist. In the second group, novice
      residents in their first 8 weeks of training (n = 11) performed similar cases
      under nearly constant attending supervision. RESULTS: The two groups seemed to
      manifest different patterns of task behavior, task density, subjective workload,
      and latency of response to the vigilance task. Response latency to the vigilance
      task increased at times of increased workload (e.g., during induction of
      anesthesia). The experienced (less supervised) providers spent significant
      amounts of time observing the monitors and the surgical field, whereas the novice
      subjects spent more time conversing with the supervising attending. Despite
      performing fewer tasks per minute (lower task densities), the novice subjects
      exhibited longer latencies of response to the vigilance light and increased
      subjective workload. Novice subjects also had longer task duration values. For
      example, postintubation, novices focused on their monitors for an average of
      twice as long as did experienced subjects (13 +/- 2 vs. 7 +/- 1 s) before moving
      on to another task. CONCLUSIONS: These techniques permitted an objective
      description of task characteristics, workload, and vigilance in anesthesia
      personnel under actual work conditions. This methodology could aid in
      understanding the factors that affect anesthesiologists' performance and may
      prove useful in assessing the progress of training.

PMID- 8291733
TI  - Closed-circuit anesthesia with sevoflurane in humans. Effects on renal and
      hepatic function and concentrations of breakdown products with soda lime in the
      circuit.
AB  - BACKGROUND: Sevoflurane reacts with CO2 absorbents, resulting in the generation
      of breakdown products. The concentrations of sevoflurane breakdown products in a
      low-flow system within 5 h have been reported, but concentrations in low-flow
      anesthesia exceeding 5 h or in closed-circuit anesthesia have not. In this study,
      the breakdown products of sevoflurane in closed-circuit anesthesia exceeding 5 h
      were examined. METHODS: Closed-circuit sevoflurane anesthesia was administered to
      ten patients. Laboratory tests of hepatic and renal function were performed
      before and after anesthesia. Gas samples were obtained from the inspiratory limb
      of the anesthesia circuit, and breakdown products were analyzed by gas
      chromatography. The temperature of the soda lime was measured during anesthesia.
      RESULTS: Among the breakdown products of sevoflurane, two products, CF2 = C(CF3)
      O-CH2F (compound A) and CH3OCF2CH(CF3)OCH2F (compound B), were detected. Compound
      A was detected in all measurements, and its concentration reached 19.5 +/- 5.4
      ppm 1 h after anesthesia and decreased after 5 h. The highest concentration
      observed for compound A was 30.0 ppm. Compound B was detected in seven of the ten
      patients; its concentration was 0.17 +/- 0.37 ppm after 0.5 h of anesthesia and
      remained at similar concentrations thereafter. The highest mean temperature of
      the soda lime was 46.0 +/- 1.7 degrees C. Postanesthetic clinical laboratory
      tests showed no abnormalities in hepatic or renal function associated with
      anesthesia. CONCLUSIONS: Two breakdown products were detected in the patients
      anesthetized with sevoflurane using a closed-circuit technique. No abnormalities
      were observed during anesthesia, and no evidence of hepatic or renal dysfunction
      was noted in postoperative laboratory tests.

PMID- 8291735
TI  - End-tidal sevoflurane concentration for tracheal intubation and minimum alveolar
      concentration in pediatric patients.
AB  - BACKGROUND: Sevoflurane is a new inhalational anesthetic agent having low
      solubility in blood and a relatively nonpungent odor. As such it should be useful
      as an inhalation induction in pediatric patients. The objectives of the study
      were to determine both the minimum alveolar concentration (MAC) and the
      concentration required for tracheal intubation (MACEI) of sevoflurane in
      pediatric patients. METHODS: The study group consisted of 36 ASA physical status
      1 elective surgical patients, aged 1-9 yr. MACEI determination: After
      establishing and maintaining the end-tidal concentration for 15 min, tracheal
      intubation was attempted with an uncuffed tracheal tube without neuromuscular
      relaxants or other adjuvants. Each concentration at which tracheal intubation was
      attempted was predetermined according to the up-and-down method (with 0.5% as a
      step size). MAC determination: The patients examined were the same as those for
      MACEI determination except that for the exclusion of those to whom neuromuscular
      relaxants or other adjuvants drugs were administered. End-tidal sevoflurane
      concentration was determined according to the up-and-down method (with 0.5% as a
      step size) and held constant for at least 15 min before a skin incision. RESULT:
      MACEI of sevoflurane was 2.69% (95% fiducial limits: 2.23% and 3.37%); MAC of
      sevoflurane was 2.03% (95% fiducial limits: 1.51% and 2.53%); and the MACEI/MAC
      ratio was 1.33. CONCLUSION: Sevoflurane appears to be suitable for use in
      pediatric patients as an induction agent, permitting tracheal intubation without
      neuromuscular relaxants.

PMID- 8291736
TI  - Safety and potency of ANQ 9040 in male volunteers.
AB  - BACKGROUND: ANQ 9040 is an experimental nondepolarizing neuromuscular relaxant.
      Initial investigations in animals had indicated a rapid onset of action
      comparable to that of succinylcholine. The purpose of this study was to assess
      the safety and potency of ANQ 9040 in humans. METHODS: ANQ 9040 was assessed in
      41 male volunteers. Anesthesia was induced with propofol and maintained with a
      propofol infusion and 60% N2O/40% O2. Neuromuscular function was measured by
      mechanomyography using train-of-four stimulation of the ulnar nerve every 12 s.
      After an initial pilot study, 23 volunteers received a single dose of ANQ 9040 of
      between 0.5 and 1.1 mg/kg to determine the dose-response relationship. The final
      10 volunteers were given twice the estimated ED95 of ANQ 9040 as a single bolus
      dose. RESULTS: The estimated ED50 and ED95 of ANQ 9040 were 0.6 and 1.3 mg/kg,
      respectively. Apart from an increase in heart rate, no important adverse effects
      were noted after ANQ 9040 administration in the dose range 0.5-1.1 mg/kg. In the
      volunteers who received 2.6 mg/kg ANQ 9040, a substantial increase in plasma
      histamine was observed. This was associated with a 12% decrease in mean arterial
      pressure and a 49% increase in heart rate. In this group, the mean onset time to
      neuromuscular block was 51.3 s. CONCLUSIONS: ANQ 9040 is a rapid-onset
      neuromuscular blocking agent. However, twice the ED95 dose is associated with
      significant histamine release and tachycardia. This finding suggests that this
      drug will not be useful in clinical practice.

PMID- 8291737
TI  - Two polymorphic microsatellites in a coding segment of the canine androgen
      receptor gene.
AB  - A 0.6-kb segment of exon 1 of the canine androgen receptor gene contains two
      polymorphic CAG tandem repeats which encode strings of glutamine homopolymers.
      The number of CAGs in each tandem repeat was determined by (1) polymerase chain
      reaction (PCR) amplification of a gene segment containing both repeats, (2)
      cleavage between repeats with restriction enzyme EcoO109I and (3) fractionation
      of the restriction fragments containing individual CAG repeats by denaturing
      polyacrylamide gel electrophoresis (PAGE). Individual genomic DNA samples from 80
      unrelated dogs (53 males plus 27 females for a total of 107 X chromosomes)
      contained 10-12 CAGs in the 5' repeats and 10-13 CAGs in the 3' repeats. Thirteen
      distinct androgen receptor genotypes were identified. Eleven (or 41%) of the 27
      unrelated females were heterozygous in one or both repeat regions, whereas all
      male samples produced single bands as expected for X chromosome markers. A total
      of seven distinct haplotypes contributed to the 13 genotypes. The 'polymorphism
      information content' or 'PIC' for this seven-allele X chromosome marker was 0.67.

PMID- 8291738
TI  - A panel of bovine, ovine and caprine polymorphic microsatellites.
AB  - We report a set of six new bovine microsatellite polymorphisms based on (CA)n
      repeats. They are highly polymorphic and thus represent valuable markers for
      genome mapping. Four of the six are polymorphic in sheep and two are polymorphic
      in goats. One, which is polymorphic in cattle and sheep and apparently
      monomorphic in goats, is X-chromosome specific and has potential value in, for
      example, sex determination and detection of chimaerism.

PMID- 8291739
TI  - Bovine casein haplotypes: number, frequencies and applicability as genetic
      markers.
AB  - Three casein loci, tightly linked on bovine chromosome 6, have been studied as
      haplotypes within families of bulls. The polymorphisms included in the study were
      CASAS1 (B, C), CASB (A1, A, A5, B), CASK (A, B, E) and a microsatellite in intron
      III of CASK. A new A5 variant of CASB, caused by a silent mutation in the triplet
      coding for amino acid 110, was detected by direct polymerase chain reaction
      sequencing. Our analysis of 306 sons and 15 sires revealed 10 different casein
      haplotypes with a cumulative polymorphic information content (PIC) of 0.78.

PMID- 8291740
TI  - Assessment of DNA fingerprinting for determining genetic diversity in sheep
      populations.
AB  - Genomic DNA, prepared from 12 animals from four sheep flocks, was digested with
      either HaeIII or HinfI and probed with three DNA fingerprinting probes. Mean DNA
      fingerprint band sharing and band frequency calculated for each flock were used
      to estimate genetic diversity. Each of the DNA fingerprinting systems showed the
      same trend in diversity within the sampled flocks, and greater diversity between
      the flocks than within the flocks. DNA fingerprinting therefore provides a useful
      measure of genetic diversity in sheep.

PMID- 8291741
TI  - Mononucleotide repeat polymorphism at the GGY locus in chicken.

PMID- 8291742
TI  - Measles, mumps, rubella immunization in egg-allergic children: a long-lasting
      debate.

PMID- 8291743
TI  - Chondrosarcoma presenting as asthma exacerbation.

PMID- 8291744
TI  - Lymphocyte subsets and antigen-specific IgE antibody in nasal polyps.
AB  - We tried to elucidate the role of allergic factors in the pathogenesis of nasal
      polyps. Nasal polyps were obtained from 22 patients with chronic sinusitis which
      included eight patients proved to have nasal allergy by history, skin test, and
      serum-specific IgE against houst dust mite. Immunohistochemical studies of
      lymphocyte subpopulations in the mucosa of nasal polyps were performed with
      monoclonal antibodies, and the concentrations of antigen-specific IgE in nasal
      polyps were measured by the fluoroallergosorbent test. In the epithelium, few HLA
      DR+ cells were constantly present. In the submucosa, pan T cell marker CD2 was
      detected more often than CD19 (B cell), and more CD8 (T suppressor/cytotoxic)
      cells than CD4 (T helper/inducer) cells were found. IgE-producing plasma cells
      were rarely present. The lymphocyte subpopulations and the levels of antigen
      specific IgE in nasal polyps were not different between the allergic and
      nonallergic groups. This suggests that allergy may not be the cause, and cellular
      immunity of antigen presenting cells and T lymphocytes, which consecutively
      induce infiltration and degranulation of mast cells by the production of
      cytokines, may be involved in the formation of nasal polyps with sinusitis.

PMID- 8291745
TI  - Measles, mumps, rubella vaccine administration in egg-sensitive children:
      systemic reactions during vaccine desensitization.
AB  - In egg-sensitive children, measles-mumps-rubella (MMR) vaccination may cause
      acute allergic reactions; therefore, current recommendations are to perform skin
      testing with the commercial vaccine before administration to egg-allergic
      children. In children with positive skin tests, desensitization with the measles
      mumps-rubella vaccine should be done in order to administer a full dose of the
      vaccine. Twelve egg-allergic children, aged 12 months to 5 years of age, were
      referred to our pediatric allergy clinic for MMR administration over a 20-month
      period. Three children had positive skin prick or intradermal tests to the MMR
      vaccine. Two of these three patients experienced systemic hypersensitivity
      reactions while undergoing desensitization to the MMR. All reactions occurred
      with injections of the undiluted vaccine. Based upon this experience, we
      recommend that egg-allergic children should continue to have cutaneous tests done
      to the MMR vaccine and careful observation during desensitization in those
      children with positive skin tests.

PMID- 8291746
TI  - Tolerability of nimesulide in aspirin-sensitive patients.
AB  - In most patients with aspirin and nonsteroidal antiinflammatory drug (NSAID)
      intolerance, antiinflammatory treatment is a clinical problem. In this study we
      evaluated the tolerance to a new nonsteroidal antiinflammatory drug, nimesulide
      (Aulin, Boehringer Mannheim, Italia), in 429 patients presenting with clear
      histories of intolerance to NSAIDs. Nimesulide has been chosen due to its weak
      inhibitory action on cyclooxygenase and its peculiar mechanism of action. We
      carried out a single-blind challenge with cumulative doses of nimesulide
      administered on three different days, until the therapeutic dose of 200 mg or
      intolerance symptoms were reached. Nimesulide has been well tolerated in 418
      subjects and only 11 patients (3.3%) showed a positive test. Our study
      demonstrates that nimesulide seems to be a suitable drug in aspirin
      hypersensitivity.

PMID- 8291747
TI  - Anaphylaxis associated with a change in premarin dye formulation.
AB  - Coloring agents are frequently added to drugs, foods, and cosmetics. If approved
      by the FDA, these additives may be added or substituted without notifying
      physicians. A patient developed angioedema, wheezing, urticaria, and dizziness
      one hour after taking the first Premarin tablet from a new refill. She had
      previously tolerated Premarin daily for 7 months without any adverse reactions.
      The new tablets were noted to be a slightly different shade of maroon and
      subsequent investigation revealed that the dye formulation had been changed (FD&C
      red #3 and FD&C yellow #6 were changed to FD&C red #40 and D&C #27). Puncture
      skin testing with a suspended tablet from the new Premarin batch was positive but
      was negative to a different drug (dye-free). Premarin skin testing in two normal
      volunteers was negative. The patient has since tolerated transdermal estrogen
      without any adverse reactions. These findings suggest that an additive in the
      Premarin tablet, most likely one of the new dyes, and not the estrogen, was the
      cause of the anaphylaxis. Physicians need to be aware that inactive ingredients
      can be changed without warning and these new constituents may cause sudden and
      potentially very severe allergic reactions to previously tolerated medication.

PMID- 8291748
TI  - Methotrexate for urticarial vasculitis.
AB  - A patient with urticarial vasculitis unresponsive to all treatments except
      systemic corticosteroids responded completely to low-dose oral methotrexate,
      allowing withdrawal of corticosteroids. Methotrexate is a proven treatment for
      other immunologic diseases, and low doses seem to carry an acceptable safety
      profile. Its use in urticarial vasculitis may be appropriate in selected
      patients.

PMID- 8291749
TI  - Prevalence of insect allergen-specific IgE in allergic asthmatic children in
      Cincinnati, Ohio.
AB  - Airborne insect antigens can represent significant outdoor aeroallergens. In this
      pilot study, allergic asthmatic children were screened by RAST for IgE directed
      against common outdoor insects. Insects studied included ant, cricket,
      grasshopper, housefly, and moth. Spiders were also tested. Three different
      extraction procedures were compared to determine which method(s) best preserves
      the allergenic proteins. RAST discs were made for each insect extract and sera
      from allergic, asthmatic and nonallergic, nonasthmatic children were tested. The
      allergic asthmatic sera had a higher percentage of isotope binding than the
      nonallergic nonasthmatic sera for all insects tested. The number of subjects with
      a Phadebas RAST score of 2 or greater was significantly higher in the allergic
      asthmatic group for moth (16 of 37, 43%), housefly (7 of 30, 23%), cricket (8 of
      41, 19%), and grasshopper (7 of 36, 19%). Only one of the 25 control sera had a
      score of 2 to moth; none of the control sera reacted to any of the other insects.
      Most positive sera tested showed cross-reactivity between insects. A few sera,
      despite showing positive RAST results to two different extracts, showed no cross
      reactivity between the two extracts, suggesting that these sera contained species
      specific IgE. These results indicate that a significant proportion of allergic
      asthmatic children have IgE that binds to extracts of moth, cricket, grasshopper,
      and housefly. Further studies are needed to determine whether these insect
      aeroallergens can produce clinically significant symptoms in sensitized atopic
      individuals.

PMID- 8291750
TI  - Nocturnal asthma.

PMID- 8291751
TI  - Histamine concentration for skin testing.

PMID- 8291752
TI  - Pine pollen hay fever.

PMID- 8291753
TI  - Ultrasonographically detected changes in equine superficial digital flexor
      tendons during the first months of race training.
AB  - The forelimb superficial digital flexor (SDF) tendons of 6 Thoroughbreds were
      examined clinically and ultrasonographically during the first 4 months of race
      training. Sonograms were interpreted clinically and by use of computer-aided
      analysis. Tendon tissue from all horses was examined histologically at the end of
      the study. Computer-aided analysis of sonograms of the SDF tendons revealed
      trends toward an increase in mean cross-sectional area and a decrease in mean
      echogenicity over time with training. An inverse relation was found between
      increase in cross-sectional area and decrease in mean echogenicity over time in
      training. Two of the trained horses developed clinical signs of mild SDF
      tendonitis. Ultrasonography revealed an increase in cross-sectional area and
      decrease in mean echogenicity of clinically affected areas of the SDF tendons of
      1 horse, compared with changes observed prior to the onset of tendonitis (these
      changes were not statistically significant). Blood vessels and lymphatics
      supplying the clinically and ultrasonographically affected tendon sites were
      large and thick-walled. These changes were not observed in the tendons of the
      other horses at the end of the study. The authors conclude that equine SDF
      tendons adapt to the early months of race training by increasing in size and
      decreasing in echogenicity, as determined by ultrasonography.

PMID- 8291755
TI  - Automated morphometric analysis of stallion spermatozoa.
AB  - Tissue variation in microscope slides made for spermatozoon analysis and
      variation introduced by the subjective techniques used to analyze these slides
      reduce the statistical power of studies that seek to use spermatozoon morphology
      to predict fertility. A simple specimen preparation method was developed to
      standardize stallion spermatozoon morphologic smears, and a new, automated
      spermatozoa morphometry instrument was used to objectively analyze the efficacy
      of the specimen preparation technique. The method achieved a standard
      spermatozoon concentration and reduced field-to-field variation in the number of
      spermatozoa analyzed. Metric measurements of spermatozoon head dimensions from
      clinically normal, fertile stallions revealed small, but highly significant,
      differences between stallions. The variation in metric measurements between
      replicate slides within stallions was small, indicating that replicate slide
      analysis probably is not necessary for clinically normal stallions. Coefficients
      of variation were generally < 11% for metric measurements between stallions, and
      were < 4% within stallions. This study revealed that a high degree of statistical
      power can be achieved when using these new, standardized specimen preparation and
      objective analysis techniques. Such power makes possible the detection of subtle
      differences between clinically normal stallions, and may facilitate accurate
      detection of abnormal fertility (ie, subfertility) in stallions.

PMID- 8291754
TI  - Sensitivity and specificity of bronchoalveolar lavage and protected catheter
      brush methods for isolating bacteria from foals with experimentally induced
      pneumonia caused by Klebsiella pneumoniae.
AB  - One indication for referral of horses to veterinary hospitals is for diagnosis of
      the microbiologic cause of pneumonia, particularly when the initial treatment
      fails. Although endoscopic methods have long been available for microbiologic
      sample collection, accuracy of these methods under these conditions have not been
      studied in detail. We compared the bacteria isolated from samples obtained by
      bronchoalveolar lavage (BAL) with those obtained by protected catheter brush
      (PCB) from foals with unilateral pneumonia induced by inoculation with Klebsiella
      pneumoniae. As part of previously described clinical trials, foals were
      administered antimicrobial therapy IM (n = 15) or vehicle IM (n = 7), and
      collection of distal airway secretion samples was conducted during the treatment
      period. Sensitivity and specificity of the sample collection methods were
      assessed by comparison of the isolates from BAL or PCB samples with isolates from
      tissue of the inoculated lung lobe, which was the most severely affected lung
      region. Sensitivity and specificity of BAL for recovery of K pneumoniae
      (challenge strain) and Streptococcus zooepidemicus (common secondary pathogen)
      was 90 and 69%, respectively, compared with 76 and 85%, respectively, for the PCB
      method. Sensitivity was significantly (P = 0.03) higher for BAL (100%) than for
      PCB (69%) for recovery of K pneumoniae (P = 0.03) from lungs. However, difference
      in the sensitivity of these methods for recovery of S zooepidemicus was not
      significant. In conclusion, BAL was a more reliable method for recovery of
      bacteria from the lungs in chronically infected foals that received antimicrobial
      treatment.

PMID- 8291756
TI  - Tracheal mucociliary transport rate in awake dogs.
AB  - To measure tracheal mucociliary transport rate (TMTR) in awake dogs, restrained
      in dorsal recumbency, 99mtechnetium-labeled macroaggregated albumin was
      administered by tracheal injection, and the cephalic movement of boluses
      containing the radiopharmaceutical was detected by a gamma camera positioned
      lateral to the dog's head and neck. The distance traveled by each bolus was
      measured, relative to external markers placed a known distance apart. Tracheal
      mucociliary transport rates were calculated by dividing the measured distance of
      radiopharmaceutical movement by elapsed time. The technique was efficient and
      well tolerated. Mean (+/- SD) TMTR was 35.3 +/- 15.9 mm/min. Significant (P =
      0.029) difference in TMTR was found between males and females, but significant
      difference attributable to age of the dog was not detected. This method of
      measuring TMTR in awake dogs has potential for evaluation of clinical animal
      patients with suspected tracheal mucociliary abnormalities.

PMID- 8291757
TI  - Brain stem auditory evoked potentials from bone stimulation in dogs.
AB  - Brain stem auditory evoked potential (BAEP) testing with air-conducted click
      stimuli can be used to diagnose sensorineural deafness in dogs if conductive
      deafness can be ruled out. Detection of conductive deafness can be performed by
      recording BAEP elicited by a vibratory stimulus transducer placed against the
      skull. Air- and bone-conducted BAEP were compared in dogs, varying bone
      stimulator placement, click polarity, and stimulus intensity. Optimal bone
      stimulator placement was determined to be over the mastoid process, followed by
      the mandible and the zygomatic arch. Condensation polarity clicks gave responses
      preferable to those elicited by rarefaction or alternating polarity. Bone
      conducted BAEP peak latencies were significantly longer than air-conducted
      latencies after correction of the latencies for the air conduction time
      accompanying air-conducted stimuli. Significant differences between stimulus
      modalities were not seen for BAEP peak amplitudes or interpeak latencies. Latency
      intensity and amplitude-intensity regressions had similar effects for both
      modalities: latencies decreased and amplitudes increased as stimulus intensity
      increased.

PMID- 8291758
TI  - Power spectral analysis and digital filtration of brain stem auditory evoked
      potentials in dogs.
AB  - Power spectral analysis and digital filtering of brain stem auditory evoked
      potentials (BAEP) were performed in dogs. The BAEP were recorded in 7 dogs, using
      alternating clicks at frequency of 20 Hz. The clicks were delivered monaurally at
      intensity of 90-dB normal hearing level. Power spectral analysis indicated that
      the frequency compositions of the averaged responses were divisible into 4
      frequency bands: A (30 to 390 Hz), B (390 to 680 Hz), C (680 to 910 Hz) and D
      (910 to 1960 Hz). The frequency limits of digital high-pass (HP) and low-pass
      (LP) filters, at which neither peak-to-peak nor absolute amplitudes were reduced,
      were 1,170 and 1,270 Hz for P1, 290 and 1,170 Hz for P2, 290 and 980 Hz for P3,
      290 and 980 Hz for P4, and 200 and 880 Hz for P5, respectively. The dual
      structure of BAEP was confirmed in dogs. Below 200 Hz for the HP filter, peak-to
      peak and absolute amplitudes of all waves were not significantly reduced.
      Therefore, this frequency may be a boundary frequency between low- and high
      frequency components of BAEP in dogs. The main source for the high-frequency
      components that constituted each positive peak and the following trough was
      derived from frequency bands C and D. The frequency limits of 200 Hz for a
      digital HP filter and of 1,270 Hz for a digital LP filter, at which amplitudes of
      all waves were not reduced, support the analog filter settings recommended for
      dogs (ie, < or = 53 and 3,000 Hz for analog HP and LP filters, respectively).

PMID- 8291759
TI  - Radiographic assessment of gastric mucosal fold thickness in dogs.
AB  - One hundred two dogs without known gastric lesions were evaluated to establish a
      reference range of gastric rugal fold thickness (millimeters). Mucosal folds were
      measurable for 63 examinations, and the length of the second lumbar vertebra was
      measured for 61 of the 63 (centimeters). Body weight was available in the case
      records of 29 dogs. Measurements of the mucosal folds were related to body weight
      (n = 29) and length of the second lumbar vertebra (n = 61) by use of linear
      regression analysis. Reference range of normal gastric mucosal fold thickness, 1
      to 8 mm, was defined by this study for dogs of any breed weighing between 2 and
      50 kg.

PMID- 8291760
TI  - Sensory receptors in the equine foot.
AB  - Two types of sensory receptors were located in the equine foot, using anatomic
      techniques. Histologic examination of stained hoof sections revealed lamellated
      corpuscles in the hoof dermis, which had many of the morphologic characteristics
      of Pacinian corpuscles. These sensory receptors were restricted to the palmar
      (caudal) aspects of the solar dermis of the heel. A second type of receptor was
      detected by use of immunocytochemistry, indicating apparently naked nerve endings
      containing the neuropeptide calcitonin gene-related peptide-like immunoreactivity
      in skin, solar dermal tubules, and the digital cushion. This peptide is an
      example of a sensory neurotransmitter contained in dorsal root ganglion cells and
      is believed to exist only in unmyelinated sensory nerve fibers. These 2
      morphologic structures may be used for detection of sensory stimuli, such as
      pressure (or vibratory senses) and pain, respectively, in horses during various
      locomotory gaits.

PMID- 8291761
TI  - Effects of sex, age, puncture site, and blood contamination on the clinical
      chemistry of cerebrospinal fluid in rhesus macaques (Macaca mulatta).
AB  - Paired CSF and serum samples were obtained from 109 rhesus macaques aged 1 to 18
      years. The CSF and serum IgG and albumin concentrations were determined, using
      radial immunodiffusion; CSF total protein and glucose were determined, using
      colorimetric methods; and Na, K, and Cl concentrations were determined, using ion
      specific electrodes. The CSF protein values were lower than those reported for
      non-human primates, and this finding was confirmed by results of agar gel
      electrophoresis. Animal age and sex had no significant effects on CSF
      composition, but serum IgG concentration increased with age. Concentrations of
      total protein, albumin, and IgG were greater, and concentrations of glucose and
      potassium were lower in CSF obtained from the lumbar rather than the cisternal
      site. Composition of CSF was not significantly altered by contamination with
      blood at values up to 10,000 RBC/microliters. The CSF albumin quotient, IgG
      quotient, and IgG index were determined and differed markedly from values
      reported for human beings, indicating that the properties and specificity of the
      blood-brain barrier may be species-specific.

PMID- 8291762
TI  - Association of Mycobacterium paratuberculosis infection with reduced mastitis,
      but with decreased milk production and increased cull rate in clinically normal
      dairy cows.
AB  - Approximately 45 Holstein cows that were Mycobacterium paratuberculosis-positive
      on the basis of fecal culture results were maintained at any one time in a 210
      cow dairy herd. Farm management participated in the New York State
      Paratuberculosis Eradication Program. Paratuberculosis-positive cows were grouped
      separately from paratuberculosis-negative cows, but they were otherwise managed
      identically. During a 1-year study, 180 paratuberculosis-negative cows and 113
      clinically normal paratuberculosis-positive cows were identified. Quarter milk
      samples (n = 6,100) were aseptically collected for microbiologic culture of
      mastitis pathogens from paratuberculosis-negative cows, and 3,129 quarter samples
      were obtained from paratuberculosis-positive cows. Dairy Herd Improvement
      Association (DHIA) records were used to monitor milk somatic cell count linear
      scores, mature equivalent milk production, new mastitis infections, and chronic
      mastitis infections. For second-lactation cows greater than 100 days in milk
      production, and increasing with age beyond that point, paratuberculosis-positive
      cows had lower mature equivalent milk production than did negative herdmates.
      Rates of new and chronic mastitis infections, as measured by DHIA linear scores
      were significantly (P < 0.05, P = 0.05, respectively) lower in cows with
      nonclinical paratuberculosis. Infected cows were culled from the herd at a faster
      rate than were paratuberculosis-negative herdmates. Therefore, paratuberculosis
      was associated with financial loss attributable to reduced milk production and
      increased culling of infected cows.

PMID- 8291763
TI  - Delayed seroconversion following naturally acquired caprine arthritis
      encephalitis virus infection in goats.
AB  - One hundred eight milking goats from a dairy that had been using a modified
      caprine arthritis-encephalitis virus (CAEV) eradication program were tested for
      CAEV antibodies by serologic methods and for proviral CAEV DNA by use of
      polymerase chain reaction (PCR) technology. All goats were free of clinical
      symptoms of CAEV infection. Twenty-seven of the 108 goats were considered
      seropositive, on the basis of ELISA results. Proviral CAEV DNA was detected,
      using PCR techniques, in mononuclear leukocytes in blood samples obtained from 25
      of the these 27 seropositive goats. Twenty of the 81 seronegative goats also had
      positive PCR test results. Ten of these goats seroconverted by 8 months later,
      and virus was readily isolated from mononuclear leukocytes in venous blood
      samples after the goats had seroconverted. Virus was also isolated from
      mononuclear leukocytes in blood samples collected from 4 of 11 goats that were
      seronegative, but had positive PCR test results. These results indicated that
      seroconversion can be delayed for many months following natural infection with
      CAEV. Delayed seroconversion appears to be a feature of CAEV infection, which may
      have direct implications for CAEV eradication programs and epidemiologic studies
      that rely on serologic methods to detect infected goats.

PMID- 8291764
TI  - Prevention of scrapie transmission in sheep, using embryo transfer.
AB  - Reciprocal embryo transfers were made between scrapie-inoculated and scrapie-free
      sheep (Cheviot and Suffolk breeds) to measure scrapie transmission via the embryo
      (using offspring from embryos of scrapie-inoculated donors and scrapie-free
      recipients) and via the uterus (using offspring from embryos of scrapie-free
      donors and scrapie-inoculated recipients taken by cesarean section). Two control
      groups of offspring, 1 from scrapie-free parents (negative) and 1 from scrapie
      inoculated parents (positive), also were included. All sheep were observed for
      clinical signs of scrapie until death or for a minimum of 60 months. Final
      diagnosis was made on the basis of histopathologic findings or results of mouse
      inoculation and/or proteinase-K-resistant protein analysis. Thirty to 61% of the
      scrapie-inoculated donor/recipient sheep within groups developed scrapie within 8
      to 44 months after inoculation. None of the scrapie-free donor/recipients,
      including those gestating embryos from scrapie-inoculated donors, developed
      scrapie. Also, none of the offspring observed to > or = 24 months of age from
      reciprocal cross, via embryo (0/67), or via the uterus (0/25), or from the
      negative-control group (0/33) developed scrapie. Fifty-six of the offspring via
      embryo, 19 of these via the uterus, and 31 negative controls survived to > or =
      60 months of age. Of the 21 sheep in the positive-control group, 2 (9.5%)
      developed scrapie, 1 at 31 months of age and 1 at 42 months of age. In the
      Cheviot offspring, the percentage of sheep carrying the short incubation allele
      ranged from 24 to 44% and the percentage in the Suffolk offspring ranged from 61
      to 83%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291765
TI  - Humoral immune responses in cats with dermatophytosis.
AB  - The IgG and IgM classes of antibodies to a water-soluble antigen preparation
      derived from Microsporum canis were determined by ELISA in the sera of 79 cats
      with dermatophytosis confirmed by results of fungal culture, and of 46 specific
      pathogen-free-derived, barrier-maintained cats with no previous exposure to
      dermatophytes. Of the 79 cats with dermatophytosis, the species isolated were: M
      canis from 72, M gypseum from 6, and Trichophyton mentagrophytes from 1.
      Concentrations of soluble M canis antigen-specific IgG and IgM were significantly
      (P < 0.05) higher in the cats with dermatophytosis than in the control cats. The
      IgG concentration was > or = 2.0 ELISA units/ml ml in 71% of the cats with
      dermatophytosis and in 9% of the control cats, whereas IgM concentration was > or
      = 4.0 ELISA units/ml in 38% of the cats with dermatophytosis and in 11% of
      control cats. There was no significant difference in either IgG or IgM values
      between the cats with M canis infection and those with other non-M canis
      dermatophyte infections.

PMID- 8291767
TI  - Repeatability of energy expenditure measurements in clinically normal dogs by use
      of indirect calorimetry.
AB  - Energy expenditure (EE) was determined, using an open-flow indirect calorimetry
      system in a group of 20 clinically normal, apparently resting, client-owned dogs.
      Five evaluations were performed over an 8-hour period to determine reliability of
      the method. The intraclass correlation coefficient was calculated as the ratio of
      within- and between-subject variances, using repeated-measures ANOVA. When only
      the middle 3 evaluations were included, the intraclass correlation coefficient
      was 0.87, indicating good reliability. The first evaluation was higher than the
      subsequent 4 evaluations for rate of O2 consumption (Vo2/kg and Vo2/kg0.75; (P <
      or = 0.01), and EE/kg and EE/kg0.75 (P < or = 0.005). The respiratory quotients
      at the first (P = 0.004) and second (P = 0.013) evaluations were different from
      the respiratory quotient at the fourth evaluation. Therefore, the first
      evaluation may not be representative of the actual EE. The mean value of at least
      3 subsequent evaluations after an adequate adaptation period (5 to 10 minutes) to
      the equipment will be useful for predicting energy requirements of apparently
      resting, clinically normal dogs.

PMID- 8291766
TI  - Aerosol vaccination of pigs against Mycoplasma hyopneumoniae infection.
AB  - Aerosol vaccination is used effectively to immunize poultry against Newcastle
      disease, but to the authors' knowledge, this vaccination procedure is not well
      studied in other species. The efficacy of IM and aerosol vaccination of pigs
      against Mycoplasma hyopneumoniae infection was evaluated. Twenty-one pigs from a
      Mycoplasma-free herd were randomly allotted by litter and body weight into 3
      groups. One group was given aerosolized phosphate-buffered saline solution (PBSS)
      by inhalation. The second group (AERO) was given aerosolized M hyopneumoniae
      vaccine by inhalation. The third group (IM) was given the same vaccine by IM
      injection. Vaccination by IM administration was repeated once, and aerosol
      vaccination was repeated twice at 2-week intervals. Two weeks after the last
      vaccination, all pigs were intratracheally challenge-exposed with 3 ml of broth
      culture containing 10(7) color-changing units (CCU) of a low-passage strain of
      virulent M hyopneumoniae. Pigs were observed daily for coughing. Four weeks after
      challenge exposure, all pigs were necropsied. Percentage of lung affected by
      gross pneumonia was measured, bronchioalveolar lavage fluid (BALF) cells were
      counted, and quantitative culture for mycoplasmas was performed on lung sections.
      Additionally, M hyopneumoniae-specific antibodies were measured in
      prevaccination, postvaccination, and postchallenge-exposure serum and BALF by use
      of indirect ELISA. Mean prevalence of persistent coughing in pigs of the AERO
      group (4.6 d/pig) was not different from that in pigs of the PBSS group (3.7
      d/pig). Prevalence of coughing in IM vaccinated pigs (1.0 d/pig) was lower (P <
      0.05) than that in pigs of the PBSS group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291768
TI  - Comparison of the effects on milk production of concurrent infection with
      Haemonchus contortus and Trichostrongylus colubriformis in high- and low
      producing dairy goats.
AB  - The impact of nematode parasitism of the digestive tract on milk output and milk
      quality was examined in dairy goats. In addition, the consequences of worm
      infection were compared in goats with different lactation performance (ie, with
      initial high or low milk production). Forty-eight goats in the second month of
      lactation were allotted equally to 2 groups. The first group was given 5,000
      Haemonchus contortus and 20,000 Trichostrongylus colubriformis larvae. The 24
      additional goats remained free of parasites. Parasitologic, serologic, and milk
      data were collected every 2 weeks for 5 months, and body condition of the goats
      was scored throughout the study. Results of strongyle egg count in feces,
      increase in pepsinogen values, and reduction in RBC count, PCV, and serum
      inorganic phosphate concentration indicated subclinical infection. This
      subclinical parasitism induced a decrease in body condition scoring and led to
      persistent decrease in milk yield, ranging from 2.5 to 10% reduction from control
      values. Changes in fat and protein contents were not detected. In contrast, the
      consequences of infection were more severe in the 6 goats with the highest milk
      production at the start of the study. Decrease in milk output ranged between 13.0
      to 25.1%, and was associated with decrease in fat content. Comparison of the
      response to parasitism in the 6 goats with the highest lactation performance and
      the 6 goats with the lowest performance indicated differences between both
      subgroups. According to parasitologic and pathologic data, high-producer goats
      had less resistance and/or resilience to infection associated with more severe
      consequences on milk production.

PMID- 8291769
TI  - Cytologic responses of Staphylococcus aureus-infected mammary glands of heifers
      to interferon gamma and interleukin-2 treatment.
AB  - Cytologic and bacteriologic responses, and changes in cytokine activity were
      evaluated in secretions of Staphylococcus aureus-infected mammary glands after
      treatment of heifers with recombinant bovine interferon gamma (rbIFN gamma) or
      interleukin 2 (rbIL-2). Two groups of 4 heifers each, experimentally infected
      with 10(7) colony-forming units (CFU) of S aureus, were injected in 2 quarters
      via the teat canal, with 10(5) U of rbIFN gamma (trial 1) or 7.5 x 10(5) U of
      rbIL-2 (trial 2) 2 weeks after experimentally induced infection; control quarters
      received phosphate-buffered saline solution. Mammary secretion samples were taken
      on days 0, 1, 2, 3, 4, 7, and 14 after cytokine infusion. Secretions were diluted
      1:10 and used to perform somatic cell counts (SCC), differential cell counts, and
      CFU enumerations, and to determine the number of leukocytes expressing major
      histocompatibility complex class-II (MHC II) antigens. In addition, mammary
      secretion samples taken on days 0, 1, and 2 were processed to obtain skimmed milk
      for evaluation of rbIFN gamma- and rbIL-2-like activities. Treatment with rbIFN
      gamma did not influence SCC, or differential or bacteria counts, or the number of
      leukocytes expressing MHC II antigens. However, rbIL-2 stimulated leukocytosis,
      which may have reduced bacteria counts early in the trial; treatment with this
      cytokine also increased the neutrophil, macrophage, lymphocyte, and eosinophil
      counts in secretions. Similarly, numbers of MHC II-positive leukocytes were
      greater in rbIL-2-treated quarters vs controls. Compared with day 0, IFN-gamma
      like activity was increased on only day 1 in both trials.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8291770
TI  - Effects of concurrent administration of phenylbutazone and flunixin meglumine on
      pharmacokinetic variables and in vitro generation of thromboxane B2 in mares.
AB  - Flunixin meglumine and phenylbutazone are nonsteroidal anti-inflammatory drugs
      commonly used for the management of colic, endotoxemia, and musculoskeletal
      disorders in equids. Although it is not usually recommended, there appears to be
      an increasing trend to use nonsteroid anti-inflammatory drugs in combination to
      enhance or prolong their effects. Therefore, we studied the effect of concurrent
      administration of flunixin (1.1 mg/kg of body weight, IV) as flunixin meglumine
      and phenylbutazone (2.2 mg/kg, IV) on the pharmacokinetics of each drug and on in
      vitro thromboxane B2 production. Pharmacokinetic variables calculated for each
      drug when given alone and in combination were similar to those reported. Serum
      thromboxane B2 production was significantly (P = 0.05) suppressed for 12, 8, and
      24 hours after administration of flunixin, phenylbutazone, and the drugs in
      combination, respectively. These results indicate that although concurrent
      administration of these drugs at the aforementioned dosages does not alter either
      drug disposition or clearance, it prolongs their pharmacologic effect.

PMID- 8291771
TI  - Pharmacokinetics and effects of repeated administration of phenylbutazone in
      neonatal calves.
AB  - Age, species, and disease state may substantially alter the disposition and
      clearance of pharmacologic agents. This is particularly important when drugs with
      low therapeutic index are used in ill neonates. Pharmacokinetic variables for
      phenylbutazone were determined in 24- to 32-hour-old healthy and endotoxemic
      calves after i.v administration of a single dose (5 mg/kg of body weight, i.v.).
      Elimination half-life was 207 and 168 hours, and clearance was 0.708 and 0.828
      ml/kg/h in healthy and endotoxemic calves, respectively. Intravenous infusion of
      endotoxin at the dose (2 micrograms/kg over 4 hours) given did not significantly
      alter any of the calculated pharmacokinetic variables. Serum thromboxane B2
      concentration was significantly (P = 0.05) suppressed for 3 hours after
      phenylbutazone administration in healthy calves and for 4 hours in endotoxin
      challenged calves. Daily administration of phenylbutazone (10 mg/kg loading, then
      5 mg/kg for 9 days) to healthy and endotoxemic calves failed to induce any
      lesions consistent with nonsteroidal anti-inflammatory drug toxicosis.

PMID- 8291772
TI  - Effects of anesthesia induced and maintained by continuous intravenous
      administration of guaifenesin, ketamine, and xylazine in spontaneously breathing
      sheep.
AB  - Anesthesia was induced and maintained in 6 Suffolk wethers by continuous i.v.
      infusion of guaifenesin (50 mg/ml), ketamine (1 mg/ml), and xylazine (0.1 mg/ml)
      in 5% dextrose in water (triple drip) to assess the anesthetic and
      cardiopulmonary effects. All sheep were positioned in right lateral recumbency.
      Dosages of triple drip used for induction and maintenance of anesthesia were 1.2
      +/- 0.02 ml/kg and 2.6 ml/kg/h, respectively. Lack of gross purposeful movement
      of sheep to electrical stimulation indicated that analgesia and muscular
      relaxation induced by triple trip were adequate for surgical procedures. Heart
      rates and arterial blood pressure remained unchanged from baseline values during
      a 1-hour period of anesthesia. Arterial blood pressures were measured indirectly,
      using an inflation cuff placed over the metatarsal artery at the heart level.
      Significant decrease in arterial partial pressure of O2 (PaO2), coupled with an
      increase in arterial partial pressure of CO2 (PaCO2), from baseline values was
      observed throughout the course of the study. Decrease in PaO2 was observed
      concomitantly with significant (P < 0.05) increase in respiration rate. Changes
      in arterial blood gas tensions observed in this study were attributed to
      respiratory depressant effect induced by anesthetic drugs and right-to-left
      shunting, perfusion/ventilation mismatch, or both caused by right lateral
      recumbency. Administration of 100% O2 via the endotracheal tube reduced the
      magnitude of the decrease in PaO2. All sheep recovered smoothly and stood within
      96.3 +/- 48.9 minutes after termination of triple drip administration.

PMID- 8291774
TI  - Accumulation of allantoin and uric acid in plasma of exercising trotters.
AB  - Plasma concentrations of hypoxanthine, uric acid, and allantoin, which are
      breakdown products of adenine nucleotides, were measured in Standardbred and
      Finnhorse trotters during and after an exercise test on a high-speed treadmill,
      after an incremental exercise test performed on a racetrack, and after a racing
      competition. Fiber-type composition of the middle gluteal muscle and the muscle
      concentrations of adenine nucleotides and inosine monophosphate were measured
      after the racetrack test. Changes in the concentration of hypoxanthine were not
      observed in any of the tests. Peak concentration of uric acid was measured
      between 5 and 30 minutes after exercise, and it was three- to tenfold higher than
      the value at rest. The variability can be explained by intensity of the exercise
      test and variation among horses. The concentration of allantoin after exercise
      was 2 to 3 times as high as that at rest, depending on the intensity of the
      exercise, although the absolute increase was about 10 times as high as the
      increase in the concentration of uric acid. Peak values of allantoin for the
      treadmill and the racetrack tests were obtained 4 to 6 minutes after exercise and
      < 30 minutes after the races. Peak concentration of allantoin correlated
      positively with the percentage of type-II (IIA+IIB) fibers in the middle gluteal
      muscle. Significant correlations were not observed between plasma concentration
      of uric acid or allantoin and muscle concentrations of adenosine triphosphate
      (ATP) or inosine monophosphate. It can be concluded that in horses, breakdown of
      ATP during and after exercise continues until allantoin is produced.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8291773
TI  - Effects of ephedrine on cardiovascular function and oxygen delivery in isoflurane
      anesthetized dogs.
AB  - The hemodynamic effects of 2 dosages of ephedrine were studied in 6 dogs
      anesthetized with isoflurane only (end-tidal concentration equivalent to 1.5
      times minimum alveolar concentration). Following instrumentation, baseline (time
      0) measurements included heart rate (HR), respiratory rate, mean arterial blood
      pressure (MAP), cardiac output, and blood gas tensions. Cardiac index (CI),
      stroke volume (SV), systemic vascular resistance (SVR), arterial oxygen content
      (CaO2), and oxygen delivery and consumption (DO2 and VO2, respectively) were
      calculated. Three dogs were given ephedrine IV at a dosage of 0.1 mg/kg of body
      weight, and 3 dogs were given ephedrine IV at a dosage of 0.25 mg/kg.
      Measurements were recorded at 5, 10, 15, 30, and 60 minutes. Each dog then
      received the alternate dosage of ephedrine, and measurements were again recorded
      at the same intervals. Effects of ephedrine varied with dosage. Neither dosage
      was associated with significant changes in pH, PaO2, PaCO2, VO2, or respiratory
      rate. Ephedrine at a dosage of 0.1 mg/kg caused transient significant increases
      in MAP, CI, SV, CaO2, and DO2, significant decreases in HR and SVR, and a late,
      slight decrease in CaO2. Ephedrine at a dosage of 0.25 mg/kg caused a greater and
      more prolonged increase in MAP, as well as increases in CI, SV, and SVR, and a
      decrease in HR. The higher dosage of ephedrine also caused a pronounced increase
      in hemoglobin concentration and CaO2, resulting in a 20 to 35% increase in DO2
      throughout the 60-minute experiment.

PMID- 8291775
TI  - Pulsatile secretion of luteinizing hormone and progesterone in mares during the
      estrous cycle and early pregnancy.
AB  - Existence of ultradian variation in serum progesterone concentration and the
      relation between progesterone and luteinizing hormone (LH) secretory patterns
      were investigated in nonpregnant and pregnant mares. Blood samples were taken
      every 15 minutes for a 24-hour period on day 8 of the estrous cycle and day 18 of
      pregnancy, respectively. Progesterone and LH concentrations were determined by
      radioimmunoassay. Progesterone was secreted in pulsatile manner in nonpregnant
      and pregnant mares. Luteinizing hormone also was secreted in a pulsatile manner
      in both groups of mares. There was little temporal relation between LH and
      progesterone pulses in either pregnant or nonpregnant mares.

PMID- 8291776
TI  - Somatosensory potentials in dogs with naturally acquired thoracolumbar spinal
      cord disease.
AB  - Somatosensory evoked potentials (SEP) were recorded at the scalp and at various
      levels along the lumbar and caudal thoracic parts of the spine in response to
      tibial nerve stimulations. The SEP were observed in 24 diseased dogs, 2 with a
      vertebral fracture, 1 with a spinal cord tumor, 1 with a vertebral tumor, and 20
      with disk herniation. Cord compression location was confirmed by myelography,
      laminectomy, or both. The clinical state had significant (P < 0.0001) influence
      on SEP characteristics. The scalp-recorded SEP latency changed only in
      association with the most severe lesions; spine-recorded SEP conduction velocity
      was lower in association with mild lesions; scalp-recorded SEP amplitude changed
      with lesions of intermediary severity. Because these 3 electrophysiologic
      variables were influenced differently by cord damage, it was possible to
      discriminate the various clinical grades by use of these techniques. However,
      dogs with signs of pain only could not be differentiated from clinically normal
      dogs. The evoked injury potential was observed in all but 4 diseased dogs, and
      its maximal amplitude corresponded, in all cases, with cord damage location.
      Increased duration (P < 0.05) of the spine-recorded SEP was associated with long
      standing problems, but not necessarily with clinically detectable malfunction.
      Use of SEP and evoked injury potential for identifying lateralized cord damage
      may be of value.

PMID- 8291777
TI  - Ultrasound-guided brain biopsy in dogs.
AB  - Ultrasound-guided brain biopsy of the cingulate gyrus and the head of the caudate
      nucleus was performed in clinically normal dogs. Dogs survived the surgery, and
      neurologic deficits were not detected in the 14-day postoperative period.
      Magnetic resonance imaging detected changes in the brain associated with biopsy
      in 9 dogs (90%) immediately after surgery and in 6 dogs (60%) 14 days after
      surgery. Fourteen days after surgery, sonography of the brain, performed through
      the skin overlying the burr hole, detected changes associated with biopsy in 9
      dogs (90%). Histopathologic changes evident in the brain 14 days after surgery
      consisted of focal malacia and hemorrhage with associated subacute
      encephalomeningitis. Postmortem examination indicated that the biopsy specimen
      was accurately obtained from the desired site in 9 dogs (90%). Tissue specimens
      suitable for histologic examination were obtained from 10 dogs (100%). Accuracy
      and low morbidity of ultrasound-guided biopsy indicate that this may be a useful
      technique for diagnosis of focal brain disease in dogs.

PMID- 8291778
TI  - Colorectal blood supply in dogs.
AB  - To determine blood supply in the area, dye or radioopaque contrast material was
      injected into the named arteries supplying the terminal colon and rectum in 10
      dogs. The cranial rectal artery appeared to supply most of the blood to the
      terminal colon and rectum. The middle and caudal rectal arteries supplied
      variable and relatively insignificant amounts. The intrapelvic rectum had a less
      adequate blood supply than did the terminal colon or proximal rectum. A ventral
      midline laparotomy and pubic osteotomy were performed in an additional 11 dogs to
      provide access to the terminal colon and rectum. When the cranial rectal artery
      was ligated and the colorectal junction was transected and anastomosed, the
      intrapelvic rectum developed marked congestion, edema, and discoloration. Rectal
      fluorescence, after IV administration of fluorescein, was either poor or absent.
      Histologically, partial- to full-thickness mucosal necrosis was evident in most
      tissue specimens taken from the rectum, and muscle necrosis was evident in some.
      These findings suggest that, in dogs, the cranial rectal artery should be
      preserved if at all possible and, if the cranial rectal artery is ligated, most
      of the intrapelvic rectum should be resected to ensure adequate blood supply to
      the anastomosis.

PMID- 8291779
TI  - Toxicity of desoxycorticosterone pivalate given at high dosages to clinically
      normal beagles for six months.
AB  - Desoxycorticosterone pivalate was administered IM to juvenile Beagles at 0, 2.2,
      6.6, or 11 mg/kg of body weight daily over a consecutive 3-day period every 28
      days (equivalent to a cumulative monthly dosage of 0, 6.6, 19.8, or 33 mg/kg) for
      6 months. Polyuria, polydipsia, and decreases in serum potassium and BUN
      concentrations were detected while the dogs were being treated. Transient
      increases in serum sodium concentrations also were detected. The treated males
      had significant decreases in body weight gain, resulting in an 18% decrease in
      body weight in the 11-mg/kg dosage group, compared with the controls. The weights
      of the adrenal glands, epididymides, and testes also were lower in the treated
      males. Organ weights for the 2.2, 6.6, and 11-mg/kg dosage groups were: 86, 79,
      and 69%, respectively, of the controls (adrenal glands); 80, 70, and 68%,
      respectively, of the controls (epididymides); and, 79, 75, and 67%, respectively,
      of the controls (testes). When normalized to body weight, these decreases in
      organ weight were still dosage-dependent, but the differences were less
      remarkable. In contrast, the relative weight (to body weight) of the kidneys
      (males and females) and of the thyroid and parathyroid glands (males) were higher
      dosage-dependently. All of the treatment-related effects, other than organ and
      body weight changes, appeared to be reversible following the cessation of
      treatment. On the basis of these results, it was concluded that treatment with
      desoxycorticosterone pivalate could be tolerated, even when given at dosage 15
      fold the therapeutic dosage of 2.2 mg/kg every 25 days.

PMID- 8291780
TI  - [Epidemiologic data on headache in children and adolescents].

PMID- 8291781
TI  - [Diagnostic approach in children and adolescents with headache].

PMID- 8291782
TI  - [Headache in intracranial hypertension syndrome].

PMID- 8291783
TI  - [Headache of migraine origin].

PMID- 8291784
TI  - [Juvenile chronic arthritis. Introduction].

PMID- 8291785
TI  - [Juvenile chronic arthritis. Systemic form].

PMID- 8291786
TI  - [Juvenile chronic arthritis. Poly- and pauciarticular forms].

PMID- 8291787
TI  - [Practical value of immunologic changes in juvenile chronic arthritis].

PMID- 8291788
TI  - [Practical aspects of the treatment of juvenile chronic arthritis].

PMID- 8291789
TI  - [Cardiovascular risk factors in childhood].

PMID- 8291790
TI  - [Cardiovascular risk factors in childhood. Arterial hypertension in childhood as
      cardiovascular risk factor. Prevention of hypertensive disease in the adult].

PMID- 8291791
TI  - [Smoking epidemiology among students and youngsters in Catalonia].

PMID- 8291792
TI  - [Hyperlipemia as cardiovascular risk factor in childhood].

PMID- 8291793
TI  - [Insulin resistance as cardiovascular risk factor in childhood and adolescence].

PMID- 8291794
TI  - [Strategies for the study and the prevention of infant sudden death in Europe].

PMID- 8291795
TI  - [Role of nutrition in the endocrine and paracrine regulation of growth].

PMID- 8291796
TI  - [Endocrinologic changes in obesity].

PMID- 8291797
TI  - [The growth hormone axis in malnutrition].

PMID- 8291798
TI  - [Evaluation of the patient with cystic fibrosis].

PMID- 8291799
TI  - [Infants with risk of sudden death. Management. The use of home monitoring].

PMID- 8291800
TI  - [Up-date on the antibiotic treatment of pulmonary infection in cystic fibrosis].

PMID- 8291801
TI  - [Other therapeutic aspects of pulmonary disease in cystic fibrosis].

PMID- 8291802
TI  - [Contribution of new drugs to the better control of epilepsy].

PMID- 8291803
TI  - [Experience with the application of a multidisciplinary (epidemiologic, clinical,
      anatomo-pathologic and medico-legal) protocol in infant sudden death].

PMID- 8291804
TI  - [Grief in infant sudden death].

PMID- 8291805
TI  - [View of the Institute of Infant Sudden Death Syndrome].

PMID- 8291806
TI  - [Severe obstructions to outflow (and inflow) of the left ventricle in the
      newborn. Anatomo-clinical forms].
AB  - Hypoplastic left heart syndrome, fundamentally aortic atresia with mitral
      hypoplasia or atresia, and related anomalies (critical aortic stenosis, mitral
      atresia and mitral stenosis) are the most important causes of severe left
      ventricular outflow and inflow tract obstruction in the newborn. We describe the
      anatomo-clinic forms of this entities and enumerate another less common causes of
      left ventricle obstruction in the neonate: mitral subvalvular abnormalities,
      cardiomyopathies and cardiac tumors.

PMID- 8291807
TI  - [Value of two-dimensional Doppler color echocardiography in mitral-ventricular
      aortic obstructive disease in the newborn].
AB  - Over the last years, the bidimensional echocardiography has assumed an
      increasingly impact in the management of heart disease in neonates. With the
      addition of Doppler technique and color flow mapping this non invasive method
      provide the most accurate definition of cardiac anatomy and physiology. It is
      particularly true in newborns with left inflow or outflow obstruction disease
      such as: pulmonary vein stenosis, divided left atrium, mitral and aortic stenosis
      or atresia, subvalvular narrowing, and hypoplastic left ventricle and aortic
      tract. The combination of these two methods contribute to recognize a specific
      left cardiac abnormalities and allow us to evaluate the therapeutical success in
      the follow up period.

PMID- 8291808
TI  - [Severe obstructions to outflow (and inflow) of the left ventricle in the
      newborn. Diagnostic and therapeutic heart catheterization].
AB  - The findings of cardiac catheterization and angiocardiography in newborns with
      severe obstruction to the left ventricular inflow and outflow tracts are
      commented. It is analyzed too the actual situation of mitral and aortic
      valvuloplasty in this patients.

PMID- 8291809
TI  - [Severe obstruction to outflow (and inflow) of the left ventricle in the newborn.
      Therapeutic possibilities].

PMID- 8291810
TI  - [Identity and role of the pediatric psychiatrist].

PMID- 8291811
TI  - [Psychosomatics in the first year of life].

PMID- 8291812
TI  - [Hospital pediatric-psychiatric consultations in chronic diseases in children].

PMID- 8291813
TI  - [Lead in the blood of a maternal-child population of the community of Madrid].

PMID- 8291814
TI  - [Air pollution and respiratory disease in children. Experience in Cartagena].
AB  - Studies on air pollution (SO2) and their influence on respiratory diseases in
      children conducted in Cartagena are reviewed and compared with those from other
      spanish cities. In Cartagena we find a weak relation between SO2 levels and
      number of children admitted to hospital for asthma attack. Indoor pollution is
      stressed, specially smoking of mother.

PMID- 8291815
TI  - [Pulmonary function and respiratory symptoms in children from the city of
      Huelva].

PMID- 8291816
TI  - [Influence of air pollution on infantile extrinsic asthma].

PMID- 8291817
TI  - [Lead and child health].
AB  - Effects of lead toxicity in children are reviewed. Several epidemiological
      studies performed in Spain are also depicted, with special attention to the city
      of Cartagena where a mean of 8.05 +/- 4.2 mcg/dl is obtained. The fact that the
      small increment observed in children living in polluted area may be due more to
      socioeconomic level (related to indoor pollution) than to outdoor pollution is
      stressed.

PMID- 8291818
TI  - Practice guidelines and reminders to reduce duration of hospital stay for
      patients with chest pain. An interventional trial.
AB  - OBJECTIVE: The acceptability, safety, and efficacy of practice guidelines have
      rarely been evaluated. Moreover, despite the recent development of guidelines and
      decision aids for patients admitted to coronary care and intermediate care units,
      few have been tested in clinical practice. DESIGN: A prospective, controlled
      clinical trial with an alternate-month design. SETTING: A large teaching
      community hospital. PATIENTS: Patients admitted to coronary care and intermediate
      care units with chest pain who were considered at low risk for complications
      according to a practice guideline (n = 375). INTERVENTION: Physicians caring for
      patients with chest pain who were at low risk for complications received
      concurrent, personalized written and verbal reminders regarding a guideline that
      recommended a 2-day hospital stay. RESULTS: Use of the practice guideline
      recommendation with concurrent reminders was associated with a 50% to 69%
      increase in guideline compliance (P < 0.001) and a decrease in length of stay
      from 3.54 +/- 4.1 to 2.63 +/- 3.0 days (0.91-day reduction, 95% CI, 0.18 to 1.63;
      P = 0.02) for all patients with chest pain considered at low risk for
      complications. The intervention was associated with a total (direct and indirect)
      cost reduction of $1397 per patient (CI, $176 to $2618; P = 0.03). No significant
      difference was found in the hospital complication rate between patients admitted
      to the hospital during control and intervention periods, and no significant
      difference was noted in complications, patient health status, or patient
      satisfaction when measured 1 month after hospital discharge. CONCLUSION: These
      results suggest that implementation of this practice guideline through concurrent
      reminders reduced hospital costs for patients with chest pain considered at low
      risk for complications. Further study of the guideline is warranted.

PMID- 8291819
TI  - Clinical efficacy and morbidity associated with continuous cyclic compared with
      continuous ambulatory peritoneal dialysis.
AB  - OBJECTIVE: To assess the clinical efficacy and morbidity of continuous cyclic
      peritoneal dialysis compared with continuous ambulatory peritoneal dialysis with
      a Y-connector as renal replacement therapy. DESIGN: Prospective, randomized
      study. SETTING: University hospital. PATIENTS: All new patients with end-stage
      renal failure consecutively entering the dialysis program from January 1988
      through July 1991 were randomly assigned to receive continuous ambulatory
      peritoneal dialysis with a Y-connector or continuous cyclic peritoneal dialysis
      and were followed prospectively. MEASUREMENTS: Patient and technique survival,
      dialysis adequacy, and (infectious) morbidity. RESULTS: Forty-one patients
      (median age, 56 years; range, 18 to 86 years) started continuous ambulatory
      peritoneal dialysis with a Y-connector (follow-up, 688 patient-months), and 41
      patients (median age, 54 years; range 21 to 76 years) started continuous cyclic
      peritoneal dialysis (follow-up, 723 patient-months). The two groups showed no
      significant differences in adequacy of dialysis (as assessed by blood pressure
      control and laboratory and neurologic variables) and patient or technique
      survival. Renal transplant was the primary reason for discontinuing the assigned
      dialysis technique in both groups. The average number of hospitalizations per
      patient-year was 1.0 using continuous ambulatory peritoneal dialysis with a Y
      connector and 0.6 per patient-year using continuous cyclic peritoneal dialysis (P
      = 0.02), with a mean duration of 10.8 and 9.6 days per admission, respectively
      (not significant). Peritonitis occurred significantly less often in those
      receiving continuous cyclic peritoneal dialysis (0.94 compared with 0.51 episodes
      per patient-year; P = 0.03). No difference in causative pathogens was observed.
      Exit site infection rate was 0.38 episodes per patient-year in both groups.
      CONCLUSION: In an unselected patient group, continuous cyclic peritoneal dialysis
      was accompanied by significantly lower rates of peritonitis and dialysis-related
      hospital admission, whereas it was as effective as continuous ambulatory
      peritoneal dialysis with a Y-connector for patient and technique survival.

PMID- 8291820
TI  - All-trans retinoic acid for acute promyelocytic leukemia. Results of the New York
      Study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of all-trans retinoic acid to
      induce complete remission and to examine its effects on duration of remission and
      survival in patients with acute promyelocytic leukemia. DESIGN: Phase II
      evaluation and comparison with historical control patients. SETTING: Tertiary
      care cancer referral center. PATIENTS: Consecutive patients with morphologic
      diagnoses of acute promyelocytic leukemia were treated during a 2-year period
      with all-trans retinoic acid (daily oral dose, 45 mg/m2). Newly diagnosed
      patients discontinued the drug approximately 30 days after they achieved complete
      remission, at which time they received three courses of combination chemotherapy.
      Patients treated with previous cytotoxic chemotherapy who then relapsed were
      continued on all-trans retinoic acid as "maintenance" therapy until they relapsed
      again. RESULTS: 56 patients entered the study: 34 were newly diagnosed and 22 had
      relapsed from previous treatment. Fifty-one patients subsequently were found to
      have the PML/RAR-alpha gene rearrangement indicative of acute promyelocytic
      leukemia, and 44 of these patients achieved complete remission (86%; 95% Cl, 76%
      to 96%). A distinctive respiratory distress syndrome developed in 13 patients
      (23%) during treatment, and 5 patients (9%; Cl, 3% to 20%) died of this
      complication. The 5 patients who lacked PML/RAR-alpha rearrangements were
      withdrawn and given chemotherapy. The 13 patients given all-trans retinoic acid
      alone as maintenance therapy (10 of whom had relapsed from a chemotherapy-induced
      remission) had a median duration of remission of only 3.5 months (range, 1 to 23
      months). Only 3 of 19 patients who relapsed from a remission induced by all-trans
      retinoic acid could be brought into remission again using this drug. The median
      survival time of all newly diagnosed patients has not been reached, but it now
      exceeds 31 months (range, 0.4 to 36+ months). No decrease in the early mortality
      rate was observed compared with a historical control group composed of 80
      consecutive, newly diagnosed patients treated only with chemotherapy at this
      center; however, overall survival was superior. CONCLUSIONS: All-trans retinoic
      acid is an effective agent to induce remission in patients with a molecular
      diagnosis of acute promyelocytic leukemia, but remissions are short and
      resistance develops rapidly. Although the incidence of early death was not
      reduced, the use of all-trans retinoic acid to induce remission, followed by
      cytotoxic chemotherapy for "consolidation," was associated with longer survival
      times when compared with historical controls treated only with chemotherapy.
      Additional studies to prevent or mitigate consequences of the "retinoic acid
      syndrome" and to identify specific patients who might benefit from earlier
      intervention with chemotherapy are needed to maximize the advantages of this
      approach.

PMID- 8291821
TI  - Predictors of smoking cessation after coronary artery bypass graft surgery.
      Results of a randomized trial with 5-year follow-up.
AB  - OBJECTIVE: To test the efficacy of a smoking cessation program for inpatients
      recovering from coronary artery bypass graft surgery and to identify predictors
      of cessation. DESIGN: Randomized, controlled clinical trial. SETTING:
      Postoperative cardiac surgery unit of a large teaching hospital. PATIENTS:
      Patients scheduled for coronary artery bypass surgery by participating surgeons
      between 1 July 1986 and 1 July 1987 who had smoked 1 or more packs of cigarettes
      in the 6 months before admission. Of 120 eligible patients, 93 enrolled and 87
      were discharged alive. All survivors were followed for at least 1 year; 94% were
      followed for a median of 5.5 years. INTERVENTION: A three-session, nurse
      delivered behavior modification program using a videotape and face-to-face
      counseling was compared to usual care. MEASUREMENTS: Smoking status was assessed
      six times in the year after surgery and 5.5 years after surgery. Self-reported
      nonsmoking was validated by saliva cotinine assay 1 and 5.5 years after surgery.
      RESULTS: No statistically significant differences were found between control (n =
      43) and intervention (n = 44) groups at baseline. One and 5.5 years after
      hospital discharge, validated continuous nonsmoking rates were identical in
      intervention and control groups (51% at 1 year; 44% at 5.5 years). Multiple
      logistic regression identified four factors that were independently associated
      with nonsmoking for 1 year: fewer than 3 previous attempts to quit (odds ratio,
      7.4; 95% Cl, 1.9 to 29.1); more than 1 week of preoperative nonsmoking (odds
      ratio, 10.0; Cl, 2.0 to 50.2); definite intention to quit smoking (odds ratio,
      12.0; Cl, 2.6 to 55.1); and no difficulty not smoking in the hospital (odds
      ratio, 9.6; Cl, 1.8 to 52.2). Nonsmoking for 5.5 years was independently
      associated with two of these factors: fewer than three previous attempts to quit
      and intention to quit smoking after surgery. Cessation was not related to
      demographic factors, daily cigarette consumption, disease severity, hospital
      course, social support, or beliefs and attitudes. CONCLUSIONS: Even without
      specific intervention, nearly one half of smokers quit for 5 years after coronary
      artery bypass surgery. A short inpatient education program did not increase this
      rate. Future efforts should target the time after discharge and focus on
      increasing motivation in patients who have repeatedly failed to quit.

PMID- 8291822
TI  - Failure of doxycycline as a causal prophylactic agent against Plasmodium
      falciparum malaria in healthy nonimmune volunteers.
AB  - OBJECTIVE: To determine whether doxycycline, 100 mg administered as a single
      daily oral dose, is effective as a causal prophylactic agent, an agent active
      against the pre-erythrocytic liver stage of Plasmodium falciparum malaria
      parasites, in healthy nonimmune persons. If effective, the recommendation by the
      Centers for Disease Control and Prevention (CDC) that doxycycline be continued
      for 4 weeks after returning from malaria-endemic areas could be shortened to 1
      week. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING:
      Medical ward at the U.S. Army Research Institute of Infectious Diseases, Fort
      Detrick, Maryland. PARTICIPANTS: 18 nonimmune, healthy, adult male volunteers,
      age 21.7 +/- 2.9 (SD) years, were enrolled in two groups, one of 8 persons and
      one of 10 persons. Six participants in the first group and 7 in the second group
      received doxycycline. The remaining participants received placebo. Two volunteers
      were dropped from the study, leaving 16 participants for analysis. INTERVENTION:
      Each participant received doxycycline, 100 mg, or placebo in a single daily oral
      dose starting 3 days before exposure to P. falciparum-infected mosquitoes and
      ending 6 days after exposure. MEASUREMENTS: Monitoring for parasitemia, plasma
      doxycycline concentrations, and mosquitoes' salivary-gland sporozoite grade.
      RESULTS: 6 of 6 (100% [95% Cl, 54% to 100%]) participants on doxycycline in the
      first group and 2 of 6 (33% [Cl, 4% to 78%]) in the second group were protected
      from malaria. No differences were found between protected and nonprotected
      participants in the doxycycline elimination half-life (T1/2) (20.8 +/- 5.0 h
      compared with 21.9 +/- 5.2 h), the steady-state average plasma concentration
      (1626 +/- 469 ng/mL compared with 1698 +/- 651 ng/mL), or other pharmacokinetic
      parameter estimates. The mean mosquito salivary-gland sporozoite grade was
      significantly higher (P = 0.02) in protected (3.5 +/- 0.3) than in nonprotected
      persons (3.1 +/- 0.1). Overall, 8 of 12 persons on doxycycline were protected
      from malaria, yielding a causal prophylactic efficacy rate of 67% (Cl, 35% to
      90%). CONCLUSIONS: A dosing regimen of doxycycline, 100 mg once daily,
      administered as a causal prophylactic agent against P. falciparum malaria in
      healthy, nonimmune volunteers, had an unacceptably high failure rate. Therefore,
      the CDC recommendation that doxycycline should be taken daily starting 1 to 2
      days before travel, during travel, and for 4 weeks after travel should still be
      followed.

PMID- 8291823
TI  - Mother-to-child transmission of human T-lymphotropic virus type II (HTLV-II).

PMID- 8291824
TI  - The management of patients with advanced carcinoid tumors and islet cell
      carcinomas.
AB  - OBJECTIVE: To determine the effectiveness of hepatic artery occlusion alone and
      with sequenced chemotherapy for patients with hepatic-dominant metastases of
      islet cell carcinomas and carcinoid tumors. DESIGN: Nonrandomized, observational
      study with follow-up from 2.5 to 10 years. PATIENTS: 111 ambulatory patients
      referred to a multidisciplinary tertiary care center who had histologically
      proven islet cell carcinoma or carcinoid tumor and symptomatic measurable
      metastatic lesions in the liver or hormonal abnormalities or both. The patients
      were ambulatory but were having substantial symptoms because of their endocrine
      syndromes or their tumors. INTERVENTION: All patients had hepatic artery
      occlusion done surgically or by catheterization and embolization. After this
      procedure, 71 patients were selected for chemotherapy with alternating two-drug
      regimens of doxorubicin plus dacarbazine and streptozocin plus fluorouracil. Main
      outcome measures of response to therapy were rates of tumor regression, rates of
      improvement in endocrine abnormalities, symptomatic improvement, and duration of
      favorable response. RESULTS: Objective regressions were observed in 60% of
      patients treated with occlusion alone and in 80% with chemotherapy added.
      Regressions were associated with substantial or complete relief from the
      endocrine syndromes. With occlusion alone, the median duration of regression was
      4.0 months and with chemotherapy added, it was 18.0 months. Any comparative
      inferences about the two treatment regimens must be guarded, because this was not
      a randomized trial and marked differences occurred in the distribution of
      prognostic factors between the patient groups. Side effects of arterial occlusion
      included fever, nausea, pain, and abnormalities in liver function. Side effects
      of chemotherapy included nausea, vomiting, leukopenia, and alopecia. CONCLUSIONS:
      Hepatic arterial occlusion can frequently produce major regression of
      neuroendocrine tumors with relief from the hormonal syndromes. Sequential
      chemotherapy may improve the rate and duration of the regression.

PMID- 8291825
TI  - Human immunodeficiency virus (HIV) infection. American College of Physicians and
      Infectious Diseases Society of America.
AB  - Knowledge about the epidemiology, diagnosis, and treatment of human
      immunodeficiency virus (HIV) infection gained since 1988 has necessitated an
      update of our previously published policies. Important advances have been made in
      the treatment of HIV infection and the acquired immunodeficiency syndrome (AIDS),
      resulting in a prolongation of the symptom-free period. Transmission of HIV
      infection from a dentist to several of his patients is believed to have occurred.
      Heterosexual transmission of HIV infection is increasing in importance. This
      statement emphasizes the ethical imperative to care for all patients; the need
      for health care professionals to adhere scrupulously to universal precautions
      because of the low but definite risk for transmission of HIV in the health care
      setting; the expanded recommendations for HIV testing to identify infected
      persons as early as possible; and the need for national leadership in public
      education, public policy development, and health care funding.

PMID- 8291826
TI  - The Canadian National Breast Screening Study: a perspective on criticisms.
AB  - Recently published 7-year results from the Canadian National Breast Screening
      Study (NBSS) generated much controversy and criticism. In women aged 40 to 49
      years at entry, no reduction in breast cancer mortality was observed when
      screened women were compared with virtually unscreened women. In women aged 50 to
      59 years, breast cancer mortality was similar when annual screening with
      mammography and physical examination was compared with annual screening with
      physical examination alone. Although NBSS results in 40- to 49-year-old women are
      similar to those from previously published screening studies, critics have
      attacked the study's design, randomization, execution, mammography, follow-up
      procedures, contamination of controls, and analysis. The absence of benefit
      observed in mammographically screened women who were 50 to 59 years old has been
      used to support criticism of mammography. Important facts have been ignored. The
      NBSS controls, aged 50 to 59 years, unlike in other studies, received thorough
      annual physical examinations. Cancer detection rates in both age groups were
      higher in the mammography than the comparison groups. Screen and interval cancer
      detection rates, sensitivity and specificity estimates, and prevalence to
      incidence ratios at first screen met or exceeded standards established by other
      screening studies. Claims that randomization was flawed, in particular, that more
      symptomatic women were assigned to mammography, are not supported by the
      distribution of descriptive variables collected before randomization was done. As
      for the "contamination" of 26% of controls aged 40 to 49 years, who reported
      receiving mammography, it is improbable that single or occasional diagnostic
      mammograms in one quarter of the control group could obliterate the benefit of
      four or five annual mammograms in almost 100% of the mammography group. Much
      remains unknown about the efficacy of breast screening.

PMID- 8291827
TI  - Ethics committees: time to experiment with standards.
AB  - Ethics committees now exist in most hospitals. Their recent establishment in many
      institutions was a response to a 1991 mandate by the Joint Commission on
      Accreditation of Healthcare Organizations (JCAHO). Proposed or new legislation in
      a few states is elevating the status of these committees, either requiring their
      use in certain cases, allowing them to substitute for judicial review, or
      granting immunity to those who follow their advice. Despite these recent JCAHO
      and legislative developments, it is widely recognized that there is a significant
      lack of data on the effectiveness of these committees and that committee members
      often lack the requisite education and skills for effective participation in case
      consultation. We argue that before granting ethics committees additional
      authority, there is a need for more research on their performance and a period of
      experimentation with quality standards governing their membership and operations.

PMID- 8291828
TI  - La cuenta.

PMID- 8291829
TI  - A new deal in HIV prevention: lessons from the global approach.

PMID- 8291830
TI  - Ulcer prevention with misoprostol in chronic NSAID users.

PMID- 8291831
TI  - Delayed-type hypersensitivity and AIDS.

PMID- 8291832
TI  - Sensitivity and specificity of the history and physical examination for coronary
      artery disease.

PMID- 8291833
TI  - Sensitivity, specificity, prevalence, and disease stage.

PMID- 8291834
TI  - Nitric oxide synthesis in meningococcal meningitis.

PMID- 8291835
TI  - Creative part-time faculty arrangements.

PMID- 8291836
TI  - Demographic changes and the Spanish-language Annals.

PMID- 8291837
TI  - Misclassification of clonidine.

PMID- 8291838
TI  - The last word on using grids.

PMID- 8291839
TI  - The last word on using grids.

PMID- 8291840
TI  - [An interview with Sylviane Muller by P Youinou. What is going to happen tomorrow
      in the field of synthetic peptides of autoantigens?].

PMID- 8291841
TI  - [Role of human immunodeficiency virus infection in 67 patients with
      tuberculosis].
AB  - This retrospective study compared the epidemiological, clinical and
      bacteriological characteristics of tuberculosis in HIV-infected (HIV+) and
      seronegative (HIV-) patients in France. It included 67 cases of tuberculosis
      observed in the hospital setting between 1985 and 1990. The 35 HIV+ patients
      (52.2%) were more frequently of European origin, while those of African origin
      were HIV-. Disseminated tuberculosis predominated in HIV+ patients, as opposed to
      pulmonary tuberculosis in HIV- patients. The tuberculin test was more often
      positive in HIV- patients than in HIV+ ones (65.6 versus 17.1%; p < 0.001).
      Direct bacteriological examination of the sputum was positive more frequently in
      HIV- than HIV+ patients (56.2 versus 22.8%; p < 0.01). A high percentage of the
      Mycobacterium tuberculosis strains isolated from HIV+ patients (20%) was
      resistant to anti-tuberculous drugs, primarily isoniazid, while no resistance was
      found in HIV- patients. The initial response to treatment and the therapy
      associated side effects did not differ between the two groups. Four relapses
      (11.4%) occurred in HIV+ patients, raising the question of the indication of drug
      prophylaxis following tuberculosis in HIV-infected patients.

PMID- 8291842
TI  - [Predictive value of the assay of serum anti-p25 antibodies in patients with
      human immunodeficiency virus (HIV-1) infection].
AB  - To assess whether monitoring of antibodies (Ab) directed against the HIV-1 p25
      core protein may be used as a predictive marker in the biological monitoring of
      HIV-infected patients, a study was performed on a transversal cohort of 68 CDC
      stage II-III, and 36 ARC and 26 AIDS stage IV patients, 37 of whom were being
      treated with anti-retroviral therapy. A second cohort included 56 patients
      followed for 3-7 years: 15 stage II-III, 11 ARC and 30 AIDS patients
      (opportunistic infections: 14; Kaposi's sarcoma: 11; non-Hodgkin's lymphoma: 5).
      p25 antigenemia and CD4+ blood lymphocyte counts were determined in parallel.
      Stage II-III patients usually had high and stable anti-p25 Ab levels, ARC
      patients exhibited more heterogeneous Ab values, while those with AIDS had very
      low values. No significant difference was observed in the serum anti-p25 levels
      of patients treated or not with anti-retroviral therapy. In patients whose CD4(+)
      cell counts were going to fall below 200/mm3 and/or who were going to progress
      towards AIDS, the Ab levels started to decrease at a rate of > 1 log U/ml
      (expressed in arbitrary units/ml) per 5 years at least 2 to 4 years,
      respectively, before the appearance of the index symptom, despite the fact that
      the CD4(+)-cell count only differed significantly between progressors and non
      progressors one year before the appearance of the disease.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8291843
TI  - [Renal parenchymatous involvements in African and Caribbean patients with human
      immunodeficiency virus infection. Apropos of 10 cases].
AB  - Between 1989 and 1990, 10 HIV-infected patients with renal involvement
      (proteinuria and/or renal failure) were followed. The 5 men and 5 women black (4
      Haitians, 3 Zairians, 2 Congolese and 1 Angolan). Their mean age was 31.7 +/- 4
      years. No known risk factor was identified and transmission was probably
      heterosexual. When renal disease was diagnosed, 4 patients had AIDS, 5 had ARC
      and 1 was asymptomatic. Kidney biopsies were performed in 7 patients: 4 HIV
      associated nephropathies (HIV AN) with segmental and focal hyalinizations, 1
      thrombotic angiopathy, and 2 interstitial nephropathies, 1 with proliferative
      glomerulonephritis. The clinical, biological and radiographic patterns of 2 of
      the remaining 3 patients were suggestive of HIV AN. Four of the 6 patients with
      HIV AN developed end-stage renal disease within 5 +/- 2.5 months; renal function
      in the other 2 remained stable for 25 and 41 months, respectively, while they
      were receiving zidovudine, but deteriorated rapidly within weeks of withdrawing
      this drug. Zidovudine may have delayed the evolution of the nephropathies in
      these patients.

PMID- 8291844
TI  - [Spastic paraplegia and polymyositis associated with HTLV-1 in a Togolese
      patient].

PMID- 8291845
TI  - [Extracerebral sites of toxoplasmosis in AIDS. Apropos of 2 cases].

PMID- 8291846
TI  - [Excavating pneumocystosis associated with cytomegalovirus pneumopathy after
      corticotherapy in human immunodeficiency virus infection].

PMID- 8291847
TI  - [Myocardial stunning during treatment with pentamidine isethionate].

PMID- 8291848
TI  - [Septic arthritis in HIV infection: 5 cases].

PMID- 8291849
TI  - [Parsonage-Turner syndrome disclosing HIV seropositivity].

PMID- 8291850
TI  - [Prevention of deep venous thrombosis in orthopedic surgery. Discussion and
      review of the literature].

PMID- 8291852
TI  - [Interferon alpha and autoimmunity].

PMID- 8291851
TI  - Interactions between leukocytes, the vascular endothelium and autoantibodies in
      the development of systemic vasculitis.

PMID- 8291853
TI  - Antiphospholipid antibodies and the antiphospholipid syndrome.

PMID- 8291854
TI  - Interferon alfa-2a therapy for airway hemangiomas.
AB  - Hemangioma is a well-recognized cause of airway obstruction in the infant with
      stridor. Corticosteroid and laser therapy are effective in stabilizing the airway
      in most cases. There are, however, some extensive airway lesions that are not
      adequately managed by these modalities. This report describes the use of
      recombinant interferon alfa-2a in 15 patients with life-threatening airway
      hemangiomas. All patients had failed corticosteroid and/or laser therapy.
      Multiple upper airway sites were involved, including the base of the tongue,
      supraglottis, subglottis, trachea, and mediastinum. Eleven patients have
      completed therapy and are doing well. Four patients have resolving lesions on the
      drug regimen. Life-threatening airway lesions unresponsive to conventional
      treatment should be considered for a trial of interferon alfa-2a.

PMID- 8291855
TI  - Limitations of electromyography and magnetic stimulation for assessing laryngeal
      muscle control.
AB  - The development of new phonosurgical techniques has increased the level of
      interest in the field of neurolaryngology. This field requires valid techniques
      for determining if muscle activation is normal. Laryngeal electromyography is
      being used more frequently to assess muscle innervation and synkinesis. Further,
      magnetic stimulation has been introduced as a noninvasive technique for nerve
      stimulation. Technical limitations that affect the clinical utility of both these
      techniques are reviewed: 1) difficulties obtaining selective and accurate
      electromyographic laryngeal muscle recordings, 2) normal variation in movement
      and muscle activation patterns within and between normal individuals when
      producing the same speech syllables, and 3) variation in laryngeal muscle
      response latencies between and within normal subjects during peripheral magnetic
      stimulation. Given the normal variation in laryngeal electromyography and
      magnetic stimulation response latencies, these techniques may not yet be reliable
      or accurate for assessing reinnervation or synkinesis following recurrent
      laryngeal nerve injury.

PMID- 8291856
TI  - Microlaryngoscopic surgery for T1 glottic lesions: a cost-effective option.
AB  - Excision of squamous cell carcinoma of the vocal cord using microlaryngoscopy
      (ML) with or without laser is a cost-effective treatment option in highly
      selected patients. A retrospective review of 50 cases of invasive and
      microinvasive squamous cell carcinoma demonstrated a failure rate of 8% (4
      patients), all of whom were successfully salvaged by hemilaryngectomy (1 patient)
      or irradiation (3 patients). Other treatment options for T1 glottic lesions
      include hemilaryngectomy or radiotherapy, yielding similar cure rates of 95% and
      67% to 93%, respectively. Investigation of the potential savings by extrapolating
      1992 health care costs into the treatment options for T1 glottic carcinoma
      resulted in costs of $12,956 per patient for ML, while hemilaryngectomy averaged
      $35,616 per patient and radiotherapy netted costs of $32,588 per patient.
      Extrapolating these costs to a theoretic group of 100 patients, ML provided
      savings of 2.4 million dollars when compared to the other treatment modalities.
      In selected patients, ML for T1 glottic cancer provides an effective therapeutic
      modality suited to our cost-conscious environment.

PMID- 8291857
TI  - Treatment of dysfunction of the cricopharyngeal muscle with botulinum A toxin:
      introduction of a new, noninvasive method.
AB  - Botulinum toxin is known as a relatively safe and efficacious agent for the
      treatment of various neurologic and ophthalmologic disorders. Since dysphagia and
      deglutition problems combined with aspiration are often caused by spasticity,
      hypertonus, or delayed relaxation of the upper esophageal sphincter (UES),
      conventional treatment including lateral cricopharyngotomy was replaced by
      localized injections of botulinum toxin into the cricopharyngeal muscle (CM) in a
      series of 7 patients. The study comprised patients with slight dysphagia caused
      by isolated hypertonus of the UES, as well as patients with severe deglutition
      disorders, complete inability to swallow, and aspiration problems. Preoperative
      diagnostic evaluation included careful history-taking, physical examination,
      cineradiography, and esophageal manometry to exclude other causes of dysphagia.
      For precise localization, injections were performed under general anesthesia
      after location of the CM by direct esophagoscopy and electromyographic guidance.
      Injections were administered into the dorsomedial part and on both sides into the
      ventrolateral parts of the muscle. Depending on the severity of symptoms and the
      intraluminal pressure of the UES, the dose varied between 80 and 120 units
      (botulinum toxin A from Dysport). The treatment outcome was evaluated by a
      disability rating score: patients' complaints were scored by subjective and
      objective parameters before and after injection. All but 2 patients experienced
      complete relief or marked improvement of their complaints. There were no severe
      side effects or postoperative complications. Local botulinum toxin injection
      proved to be an effective alternative treatment to invasive procedures for
      patients with isolated dysfunction of the UES, and also for patients with more
      complex deglutition problems combined with aspiration.

PMID- 8291858
TI  - Composite reconstruction of the esophagus and hypopharynx after severe caustic
      injury.
AB  - The ingestion of caustic materials may cause burns and subsequent strictures of
      the esophagus. Depending on the extent of the injury, the stricture may require
      dilation, excision, or bypass with an esophageal replacement. There is also a
      risk of esophageal dysfunction, perforation, and malignancy. Here is presented a
      case of a burn so severe that the hypopharynx was deformed and the esophagus
      destroyed. Composite techniques restored complete gastrointestinal continuity
      while maintaining excellent swallowing function.

PMID- 8291859
TI  - Lymphatic drainage system after left radical neck dissection.
AB  - The thoracic duct is the main lymphatic vessel that drains most of the body's
      lymph and all of the intestinal chyle into the venous system. The thoracic duct
      may be ligated during left radical neck dissection (RND) without any significant
      sequelae. The lymphatic system must, therefore, have collateral channels. The
      present study shows an increased incidence of pleural effusion after left RND
      when compared to right RND. We suggest that this represents the inability of the
      collateral system to immediately accommodate the increased volume of chyle.

PMID- 8291860
TI  - Does topical antibiotic prophylaxis reduce post-tympanostomy tube otorrhea?
AB  - Purulent otorrhea is the most common complication of tympanostomy tube (TT)
      insertion. It may occur in the postoperative period or at any time during the
      sojourn of the tube. The efficacy of topical antimicrobial prophylaxis against
      purulent postoperative otorrhea (PPO) has been examined in 5 prospective,
      randomized studies; all demonstrated a reduction in PPO from topical
      antimicrobial prophylaxis, but in only 1 study was the difference statistically
      significant. Because the 5 studies used 2 different experimental designs--by
      patient, and by-ear--a single meta-analysis could not be done. However, the by
      patient studies met the criteria for meta-analysis, which demonstrated a combined
      odds ratio of 0.12 (95% confidence interval 0.04 to 0.37, p = .0002). This
      represents an 85% reduction in otorrhea, which is judged to be clinically as well
      as statistically significant. We conclude from the available evidence that
      prophylactic use of topical antimicrobial agents following TT insertion
      consistently reduces the rate of PPO. However, the low incidence of PPO and the
      heterogeneity of the published studies prevent making a final judgment for or
      against the continued use of these agents. Therefore, given that these
      potentially ototoxic agents are frequently administered to prevent postoperative
      otorrhea, further study of this subject is warranted. In the meantime, we
      recommend judicious use of these agents following TT insertion in those cases at
      higher risk for PPO, namely those with mucoid or purulent effusion.

PMID- 8291862
TI  - Abnormal enhancement in the region of the vestibular aqueduct on magnetic
      resonance imaging in a cerebellopontine angle meningioma.

PMID- 8291861
TI  - Nasal and otologic effects of experimental influenza A virus infection.
AB  - Past studies showed that experimental rhinovirus colds in adults resulted in
      eustachian tube dysfunction and abnormal middle ear pressures. In the present
      study, the symptoms and pathophysiologic findings accompanying experimental
      influenza viral infection were documented. A total of 33 healthy adult volunteers
      were intranasally challenged with an influenza A/Kawasaki/86 (H1N1) virus and
      cloistered over a 9-day postchallenge period to monitor for evidence of
      infection, signs and symptoms of illness, and the extent and frequency of
      pathophysiologic responses of the nose, eustachian tube, and middle ear. Results
      showed a protective effect of high (> or = 16) prechallenge specific
      hemagglutination-inhibition antibody titer on the rate of infection and the
      magnitude and extent of provoked symptoms and pathophysiologic findings. Infected
      subjects with low (< 16) prechallenge serum antibody titers (n = 21) developed
      significant respiratory illness. These subjects also had objectively measurable
      increases in nasal secretion production, and decreased nasal patency and
      mucociliary clearance rates. More than 80% of the infected subjects developed
      eustachian tube dysfunction, and approximately 80% had middle ear underpressures
      of less than -100 mm H2O on study days 4 and 5. Five of 21 infected subjects with
      low prechallenge antibody titers had otoscopic evidence of otitis media with
      effusion. These results support a causal role for viral upper respiratory tract
      infection in the pathogenesis of otitis media, possibly mediated by the early
      development of eustachian tube dysfunction and abnormal middle ear pressure.

PMID- 8291863
TI  - Fibrous dysplasia of the temporal bone.

PMID- 8291864
TI  - Desmoplastic melanoma.
AB  - Desmoplastic melanoma is an uncommon type of malignant melanoma that has a
      predilection for the skin of the head and neck. Because of a progressive
      metaplasia of melanocytes and an accompanying desmoplasia, the neoplasm can be
      mistaken for benign or malignant soft tissue lesions. The neurotropism exhibited
      by many desmoplastic melanomas is a strong adverse factor for prognosis;
      otherwise, the biologic behavior is not unlike that of conventional melanomas.

PMID- 8291865
TI  - Comparison of the chondrogenic potential of free and vascularized perichondrium
      in the airway.
AB  - Revascularized perichondrium or periosteum may be the ideal graft to repair
      severe laryngotracheal stenosis because of its pliability, potential for bone or
      cartilage formation, resistance to infection, and rapid mucosalization. To begin
      our evaluation of these grafts in airway reconstruction, this study was designed
      to quantify the chondrogenic capacity of free and vascularized perichondrium
      placed in the airway. In a rabbit model, free auricular perichondrium (N = 16)
      produced a mean cartilage thickness of 0.15 mm, whereas vascularized auricular
      perichondrium (N = 18) produced a mean of 0.45 mm at 8 weeks (p < .0001). In a
      third group of rabbits (N = 4) vascularized auricular perichondrial grafts were
      subjected to a 2-hour intraoperative ischemic insult in order to simulate the
      ischemia of revascularization. The mean cartilage thickness at 8 weeks was 0.50
      mm. We conclude that in the rabbit model, vascularized perichondrium provides
      significantly more cartilage than free perichondrial grafts.

PMID- 8291866
TI  - Superficial urinary bladder cancer. Results from the Finnbladder studies and a
      review on instillation treatments.
AB  - At present, about 80% of primary, newly diagnosed urinary bladder cancers are
      local (NOMO), i.e., potentially curable. Not less than two thirds of all are
      superficial cancers (TIS, Ta, T1), and thus subjects of conservative, local
      treatments. Carcinoma in situ (TIS/CIS) has three clinical manifestations: 1)
      primary TIS is found without a previous history of bladder cancer, 2) secondary
      TIS is found during the follow-up of an earlier cancer, and 3) concomitant TIS is
      found simultaneously with a papillary tumour. Otherwise, there are controversial
      diagnostic and therapeutic attitudes on TIS. Concerning the primary diagnosis and
      grading, the reliance on cytological possibilities varies in separate centres.
      "Wait-and-see policy" might be justified in mild dysplasia Grade 1, whereas both
      the TIS Grade 2, and TIS Grade 3, are real malignancies which need a more
      effective treatment than transurethral resection (TUR) alone. Under a close
      control, intravesical chemo- and immunotherapy with doxorubicin (ADM), mitomycin
      C (MMC) and bacillus Calmette-Guerin (BCG) offer an alternative to cystectomy.
      However, it remains to be seen in the future whether combined or alternating
      instillations will give a still better return. By contrast, the principal
      treatment of visible superficial (Ta and T1) cancer is TUR, which can be easily
      repeated. Most recommended strategy for Grade 3 T1 cancer seems to be the same.
      Anyhow, the high frequency of recurring tumours and the tendency to simultaneous
      progression in specific categories of Ta-T1 cancer have led to adjuvant
      prophylactic instillation treatments. Currently, both local cytostatics (ADM and
      MMC in the present series), and immunoagents (BCG) have been proven
      safe.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291867
TI  - Hemi-Kock reconstruction following cystectomy: experience and results from a
      small urological unit.
AB  - Between December 1988 and January 1992, 11 men underwent lower urinary tract
      reconstruction by means of the hemi-Kock ileal reservoir following radical
      cystoprostatectomy (ten patients) and subtotal cystectomy (one patient). Six of
      the 11 patients developed an early postoperative complication, with a fatal
      outcome in two of them. One patient succumbed to subarachnoidal bleeding and one
      to septic shock. During the follow-up, another two men died of advanced bladder
      carcinoma. The late complication rate was low. Most patients regained their
      continence within six months. A good continence was achieved in all the nine
      remaining patients during the day and in six of them at night. This experience
      suggests that the hemi-Kock reservoir is a useful method for the urinary tract
      reconstruction following cystectomy.

PMID- 8291868
TI  - Diagnostic and therapeutic aspects of adenocarcinoma of the urinary bladder.
AB  - Twenty cases of adenocarcinoma of the urinary bladder were diagnosed and treated
      at Oulu University Hospital between 1978 and 1991, comprising nine primary
      adenocarcinomas (three urachal and six non-urachal) and 11 of extravesical origin
      (six from the colon, four from the prostate and one from the perineal skin). The
      prognosis for primary adenocarcinoma after radical surgery was relatively
      favourable during a follow-up of mean 54 months, but extravesical origin carried
      a high mortality rate. The diagnostic and therapeutic aspects are discussed.

PMID- 8291869
TI  - Polyestradiol phosphate (160 mg/month) or LHRH analog (buserelin depot) in the
      treatment of locally advanced or metastasized prostatic cancer. The Finnprostate
      Group.
AB  - The clinical efficacy, cardiovascular complications and mortality of
      polyestradiol phosphate (PEP) 160 mg/month i.m. were compared with the
      luteinizing hormone releasing hormone (LHRH) analog, buserelin, in a prospective,
      randomised multicentre study including 147 patients with prostatic cancer. The
      cumulative non-progression rate at three years was 0.53 in the PEP group and 0.70
      in the LHRH group. The mortality from cardiovascular diseases was the same in the
      two treatment groups. The parenterally given PEP was not associated with an
      increased risk of cardiovascular complications. The dosage of PEP 160 mg monthly
      seems, however, to be insufficient in the treatment of prostatic cancer.

PMID- 8291870
TI  - Cytostatic effect of interferon alpha on human bladder cancer cells in vitro. A
      flow cytometric study.
AB  - The cytostatic activity of interferon a-2b on human transitional cell cancer T24
      cells was examined using bioluminescence assay. Interferon a in a concentration
      of 1 x 10(6) IU/ml had a remarkable cytostatic effect already in two-day
      cultures, and this effect increased still further when the cells were incubated
      for three and five days. In the flow cytometric study, the percentage of cells in
      the S-phase fraction (SPF) remained at the same level after three days of
      incubation with interferon a (43.6 +/- 2.7), but decreased significantly in the
      control cell population (25.6 +/- 1.5). If interferon a was washed away after two
      hours and incubation was continued for three days, the percentage of cells in the
      SPF was also significantly higher (43.6 +/- 3.3) than that in the control group
      of cells (P < 0.01).

PMID- 8291871
TI  - Parenchyma-conserving surgery for renal cell carcinoma.
AB  - Between 1969 and 1992, 32 patients underwent conservative surgery (partial
      nephrectomy or enucleation) for renal cell carcinoma (RCC). Elective parenchyma
      conserving surgery (n = 10) was done in patients with small, peripheral kidney
      tumors and a normal contralateral kidney. Cancer in a solitary kidney, bilateral
      tumors, dysfunctional contralateral kidney or chronic renal failure were
      imperative indications (n = 22) for conservative surgery. In the elective group
      the tumors were 15-100 mm (mean 37 mm) in diameter, in the imperative group 5 to
      200 mm (mean 41 mm). The follow-up was 0.2-192 months (mean 48.7 months). Nine of
      22 (41%) patients in the imperative group have died of RCC. There were no renal
      cancer related deaths in the elective group. The 5-year cause-specific survival
      rates for the elective and imperative groups were 100% and 46%, respectively. Two
      patients in the elective group have died of unrelated causes. Local recurrences
      developed in three of 22 patients in the imperative group after a mean of 5.4
      years; two of them had von Hippel-Lindau disease with bilateral RCC. Conservative
      surgery seems to be a feasible option in small peripheral kidney tumors.

PMID- 8291872
TI  - Contact Nd:YAG laser and regional renal hypothermia in partial nephrectomy.
AB  - Contact Nd:YAG laser resection using the sapphire tip is nowadays a well-known
      method of partial nephrectomy. Our material consists of six patients (seven
      resections). The indication for the operation was a renal carcinoma in five
      patients (six resections) and renal changes of von Hippel-Lindau syndrome in one
      patient. Occlusion of the renal artery insured a good intraoperative haemostasis.
      This improved the cutting properties of the laser and made it more accurate. Low
      energy levels could be used. Thus the destruction of the renal parenchyma will be
      reduced. The mean follow-up time was 15.3 months. No local recurrences or distant
      metastases have been detected. In our hands the Nd:YAG contact laser combined
      with renal hypothermia is superior to traditional methods of partial nephrectomy.

PMID- 8291873
TI  - Pharmacotesting with high dose prostaglandin E1 in impotence.
AB  - The diagnostic value of pharmacotesting in impotence is controversial. The
      results of high dose prostaglandin pharmacotesting were compared with those of
      colour duplex Doppler scanning and pharmacocavernometry in 82 impotent patients
      and 10 control subjects. Based on the results of 10 control subjects, the
      prostaglandin test was defined as positive if intracavernous pressure 200 minutes
      after injection of 40 micrograms prostaglandin E1 was > or = 42 mm Hg and
      negative if intracavernous pressure was < 42 mmHg. The test was repeated in 29
      subjects and classified results were consistent in 24 subjects (86%, k = 0.65).
      The test was negative in 52 out of 56 patients (sensitivity 93%) with
      vasculogenic impotence (arteriogenic and/or cavernovenous factor involved) and
      the test was positive in 21 out of 26 patients (specificity 81%) with non
      vasculogenic impotence (arteriogenic or cavernovenous factor not involved). The
      majority, 27 out of 31 patients (87%) with arteriogenic impotence showed
      simultaneous dysfunction of cavernovenous occlusion mechanism. In conclusion,
      pharmacotesting with high dose prostaglandin is a useful screening test of
      vasculogenic impotence.

PMID- 8291874
TI  - Cavernous auto-injection therapy with prostaglandin E1.
AB  - During 1990-1992, 176 consecutive patients (aged 18-83 years, mean 53 years) with
      erectile dysfunction were personally investigated by the author in the private
      office setting at Eira Hospital. Pharmacotesting with 20 micrograms prostaglandin
      was positive in 89 of 138 patients (64%) tested. Eleven per cent of the patients
      complained of pain during erection. Of 131 patients, who initially were offered
      auto-injections as a primary treatment modality, 99 (76%) began the therapy.
      Seventy-four per cent of the patients continued auto-injections after three
      months. The overall efficacy of prostaglandin E1 to induce adequate erections for
      sexual intercourse was estimated to be 71%. One prolonged erection without
      medical intervention and no penile fibrotic lesions were recorded. In conclusion,
      cavernous auto-injection therapy with prostaglandin E1 is a well accepted,
      effective and safe treatment alternative in psychogenic as well as organic
      impotence. Every impotent patient should be informed of this therapy.

PMID- 8291875
TI  - Zinc compounds in urethral catheters. A possible source of toxicity?
AB  - The cytotoxicity of latex urinary catheters has been earlier documented. During
      the manufacturing process tens of chemicals are added to the natural rubber base.
      Several of the accelerators and other chemicals used have carcinogenic and acute
      toxic effects. Some of the accelerators are zinc compounds. In the present study,
      the cytotoxicity and zinc concentration of 68 latex catheter extracts were
      analysed. The siliconized latex catheters were the most toxic, and a correlation
      was seen between the IC50 values and the zinc concentration. The good
      manufacturing practice (GMP) has to some extent resolved the cytotoxicity problem
      of latex urinary catheters. There is, however, still a need to reformulate the
      manufacturing process and to find new catheter materials to meet the new EN
      standards concerning the biological safety of urinary catheters.

PMID- 8291876
TI  - Clean intermittent self-catheterization after urethrotomy for recurrent urethral
      strictures.
AB  - Although endoscopic optical urethrotomy is the primary treatment for urethral
      stricture, it is associated with a high recurrence rate, and the essential
      problem is how to stop the scar from shrinking after cutting. In a controlled
      study the effect of treatment of recurrent urethral stricture by internal
      urethrotomy followed by clean intermittent self-catheterization (CIC) for 6 or 12
      months was compared in 25 and 24 patients, respectively. Patients learnt easily
      how to perform CIC: only one patient was not able to do it at home. All patients
      were evaluated by uroflowmetry before and immediately after urethrotomy, and 3,
      6, 9 and 12 months later. Recurrence was defined as the need for further
      treatment. There was no difference in the recurrence rate between the two groups,
      but the maximum flow rate was significantly lower at 12 months in the patients
      who had ceased catheterization at six months. Complications included in two
      patients asymptomatic bacteriuria and in 10 patients symptomatic urinary
      infection. CIC is a very satisfactory method of managing patients with recurrent
      stricture, it is easy to learn, it prevents a decrease in the maximum flow rate
      and can thus be applied to most patients instead of regular bouginage. On the
      basis of the present study we could not determine any optimal time for the
      duration of CIC after urethrotomy, or whether it has any effect on the natural
      course of the disease.

PMID- 8291877
TI  - Aetiology, diagnosis and treatment of patients with renal trauma. A survey on
      patients in the Tampere area during two decades.
AB  - A material of 185 renal traumas treated during 1972-1991 was analyzed. A typical
      patient was a young man; the mean age was 30 years. The most common aetiology was
      traffic accident (45%). Penetrating traumas were rare (2%). The most common and
      significant finding was macroscopic haematuria, but the absence of haematuria did
      not exclude renal trauma. Unexpected findings were seen in 7% of cases. The most
      common renal injuries were contusion (69%) and laceration (20%) which were mostly
      treated conservatively (85%) with good results. Only 15% of patients were
      operated. Renal complications were few both in the conservatively and in the
      surgically treated patients. No mortality was seen.

PMID- 8291878
TI  - Prognostic factors of advanced prostatic carcinoma.
AB  - Eighty-two patients with advanced prostatic carcinoma were treated with a long
      acting luteinizing hormone releasing hormone (LHRH) agonist (Zoladex depot,
      Zeneca Pharmaceuticals, England). The outcome of the treatment was monitored on
      the basis of the following prognostic factors: local stage, number of bone
      metastases, histological differentiation grade and prostate-specific acid
      phosphatase (PAP), alkaline phosphatase (AF) and testosterone levels. The
      patients were followed-up until disease progression or until death. The mean
      weight of the prostate decreased from 48.1 g to 17.4 g (P < 0.00001) during the
      first year of treatment. Statistically there was a significant difference in
      regard to appearance of progression between different clinical stages (P <
      0.00001). The prognosis was poorest in patients with more than 10 metastases at
      the primary stage. If the PAP level was initially higher (over 20 micrograms/L),
      the prognosis was very poor. Statistically there was a significant difference
      between the high PAP level and the slightly elevated or normal PAP (P < 0.02 and
      P < 0.005, respectively). Alkaline phosphatase (AF) appeared to be a good
      prognostic factor. The prognosis was particularly poor, if the AF level exceeded
      1000 U/L (P < 0.00001 and P < 0.05, compared with normal AP and slightly elevated
      AP level, respectively). Surprisingly, a high pre-treatment testosterone level
      worsened the prognosis during the LHRH agonist treatment (P < 0.01, compared to
      patients with normal testosterone level). This is a new finding and controversial
      to the findings reported before.

PMID- 8291879
TI  - Treatment of urinary stones by extracorporeal shock wave lithotripsy.
AB  - A total of 1641 ESWL-treatments were performed in 948 patients at Helsinki
      University Central Hospital between June 1989 and December 1991. In a series of
      816 patients and 1287 treatments with data available 681 (76.4%) stones were
      located in the kidney, 208 (23.3%) in the ureter, and three (0.3%) in the urinary
      bladder. Auxiliary procedures were performed in 156 (19.1%) and repeated
      treatments in 300 (36.8%) patients. The most common complication was intensive
      pain during the procedure in 138 (16.9%) patients. The first 139 patients were
      followed until six months after their last ESWL-procedure. The six-month stone
      free rates of renal and ureteric stones of these patients were 67.4% and 86.7%,
      respectively. The overall six-month clearance rate was 72.4%.

PMID- 8291880
TI  - [Scapular crest. Anatomical and harvesting technique].
AB  - The value of the scapular crest pedicle bone graft has been clearly established
      by clinical cases over the ten last years. The crest is compared to cortico
      diaphyseal bone because of its properties, which are different from those of
      other parts of the scapula. The centromedullary space is vascularized by its own
      vascular system which penetrates the bone at the site of emergence of the
      cutaneous vessels of the scapular flap. The inferior portion is covered, in
      children by a voluminous apophysis which remains cartilaginous for a long time.
      Harvesting difficulties due to vascular and muscular characteristics are
      described in this paper.

PMID- 8291881
TI  - [Repair of mammary ptosis by insertion of an internal absorbable support and
      periareolar scar].
AB  - Since 1989, we have operated 38 patients with breast ptosis with or without
      hypertrophy according to a technique which leaves a periareolar scar. The
      principles of this technique are: periareolar skin resection, dissection between
      the skin and gland over the entire surface of the gland, mastopexy, insertion of
      an absorbable mesh onto the anterior surface of the gland which constitutes an
      internal support, closure by the isolated periareolar scar. In our hands, this
      technique cannot be used to treat all forms of breast ptosis, but gives excellent
      results in certain selected indications such as tuberous breasts, breast
      asymmetry with one normal breast, ptosis and moderate hypertrophy. The
      reliability of the technique despite extensive dissection is remarkable and the
      stability with a follow-up of 3 years is good when the indication has been
      correctly defined. In comparison with other periareolar techniques, our approach
      has the advantage of not leaving any nonabsorbable elements in the wound, the
      only guarantee of reliability of clinical and radiological surveillance of the
      breast.

PMID- 8291882
TI  - [Forum on tissue expansion. Expansion of the scalp. Surgical techniques and
      clinical applications].
AB  - Repair of all forms of alopecia is one of the principal applications of scalp
      expansion. The authors have inserted 400 expansion prostheses, including 20 in
      the scalp. The surgical technique, choice of material and various types of flaps
      are described and illustrated by clinical cases of extensive alopecia.

PMID- 8291883
TI  - [Forum on tissue expansion. Value of cutaneous expansion for the covering of
      synthetic materials used in cranioplasty. Apropos of a case].
AB  - The authors present a case of cover of synthetic material by expanded skin. In a
      context of post-sepsis revision, this cover proved to be of excellent quality,
      superior to normal scalp. The specific characteristics of tissue expansion may
      possible explain, in this context, the superiority of the expanded skin. The
      authors intend to adopt a similar therapeutic approach is such a situation should
      arise in the future.

PMID- 8291884
TI  - [Forum on tissue expansion. Repair of sequelae of facial burns by cervical
      cutaneous expansion].
AB  - Burn scars of the lower part of the face are a difficult problem in plastic
      surgery. Full thickness skin graft or local flaps usually give poor cosmetic
      result. Over the last 5 years, we used 24 skin expanders in the neck area to
      cover burn scars of the chin and jaw. Discussion of the method and 4 cases are
      reported.

PMID- 8291885
TI  - [Forum on tissue expansion. Expansion of the upper limb].
AB  - The authors report their experience of skin expansion of the upper limb based on
      a series of 42 operated patients: shoulder (8 cases), arm (19 cases), forearm (5
      cases) and hand (8 cases). The operative protocol must be rigorous in terms of
      the choice of prosthesis (shape and size) and the type of valve (internal or
      external) and in terms of the technique of insertion of the expansion prosthesis
      (short incision in healthy skin) and harvesting of the expanded flap (sliding
      draping flap rather than rotation flap). The indications are varied: unsightly
      scars and sequelae of burns, congenital naevi, syndactyly, resurfacing and
      preparation for a secondary surgical procedure (implant of a prosthesis,
      neurolysis, tenolysis). There were few complications with only 2 major
      complications resulting in failure of this technique.

PMID- 8291886
TI  - [Forum on tissue expansion. Fast continuous expansion. A 3-years evaluation of
      its use from a retrospective study of 78 cases].
AB  - The authors report their experience of cutaneous expansion in a retrospective
      study of 78 cases. They compare the two methods usually applied: discontinuous
      slow expansion in two thirds of cases versus rapid continuous expansion in one
      third of cases. Both methods, as they are defined in the department, are
      described. Statistical analysis revealed two important facts: the complication
      rate was considerably lower in continuous expansion. Length of hospital stay was
      similar for both techniques. The results, not yet studied in a strictly
      scientific way, do not appear to argue against continuous expansion. Rapid
      cutaneous expansion may be considered to be a valuable technique in the future,
      but it must be chosen for certain people only and must be adapted to each
      patient.

PMID- 8291887
TI  - [Forum on tissue expansion. Breast reconstruction by expansion in a young woman
      with sequelae of thoracic amniotic disease. Apropos of a case].
AB  - Amniotic disease or congenital skin sulci disease is a clinical entity covering a
      broad spectrum of malformations, usually involving the limbs, skull and face.
      This malformation is exceptional in the thorax. The authors report the case of a
      22 year old woman with sequelae of thoracic amniotic disease, consisting of
      unilateral mammary aplasia, atrophy of the pectoralis major and latissimus dorsi
      muscles and deformity of the homolateral thoracic skeleton. They describe the
      breast reconstruction performed by tissue expansion in this patient.

PMID- 8291888
TI  - [Forum on tissue expansion. Are tissue expansion and radiotherapy compatible?
      Apropos of a series of 50 consecutive breast reconstructions].
AB  - Tissue expansion has become a method of choice for immediate or delayed breast
      reconstruction. The compatibility of radiotherapy and tissue expansion is a
      growing problem. We analyse a series of 50 breast reconstructions by expansion,
      24 without radiotherapy and 26 with radiotherapy. For the 24 patients without
      radiotherapy, very satisfactory cosmetic results were obtained in 71% of cases
      with 21% of stage III-IV capsular contractures and 8% of failures. For the 26
      patients with a history of radiotherapy, very satisfactory cosmetic results were
      obtained in 65% of cases with 20% of capsular contractures and 10% of failure.
      20% of cases also required a myocutaneous flap to complete the reconstruction.
      The complications related to radiotherapy are due to radiation lesions of
      endovasculitis and destruction of the network of elastin fibres. They result in
      the impossibility of filling the expander, deformation of the thoracic cage,
      expansion without projection, thinning of the tissues over the prosthesis and
      necrosis and exposure requiring the use of a myocutaneous flap. In conclusion,
      signs of radiation dermatitis constitute a contraindication to tissue expansion,
      which is nevertheless possible, but with a higher risk of complications.
      Irradiation to an expansion prosthesis is associated with an unacceptable
      complication rate.

PMID- 8291889
TI  - [Forum on tissue expansion. Tissue expansion and radiotherapy. Changes in
      epidermal mitotic index induced by expansion and/or irradiation in the rat].
AB  - In order to study the influence of irradiation during skin expansion, an
      experimental protocol using 15 laboratory rats was undertaken. The present
      experiment was designed to evaluate the mitotic activity of the epidermis by in
      vitro autoradiography. The mitotic activity was assessed by the Labelling Index.
      Experimental data concerning expansion were shown to be consistent with the
      literature. When a high dose of radiation was delivered to the skin during
      expansion, a significant increase was observed in the mitotic activity of the
      epidermis. The range of variation was equivalent to that expected in normal skin.
      This is the first experimental result in favour of irradiation during skin
      expansion. However, no conclusion can be drawn concerning the clinical
      applications (immediate breast reconstruction using tissue expansion) due to the
      limitations of the present experiment.

PMID- 8291890
TI  - [Forum on tissue expansion. Conclusion. How to master expansion...].
AB  - The author presents several reflections based on more than ten years of
      experience with skin expansion. In order to master expansion, a number of rules
      must be respected at each step of the procedure:--start by defining the treatment
      plan,--choose appropriate material,--apply the expander(s) according to a
      rigorous approach,--prevent and treat all complications,--ensure sufficient
      expansion to eradicate the entire lesion. The authors views are illustrated by
      particular clinical examples using expanded transposition flaps: treatment of
      extensive baldness, ear reconstruction, repair of major sequelae of thoraco
      abdominal burns.

PMID- 8291891
TI  - [Forum on tissue expansion in practice... Plastic surgery in full expansion].

PMID- 8291892
TI  - [Tissue expansion].

PMID- 8291893
TI  - [The trapezoid face: transversal excess in the maxillary area].
AB  - The patient who consults for "big cheeks" usually desires correction for an
      excess of tissue in the masseter region. First all neoplastic pathologies
      recognized by their unilateral asymmetry are excluded in order to focus on
      bilateral phenomena. Three anatomical elements can be responsible either alone or
      in association for this excess: the parotid gland, the masseter muscle and the
      angle of the jaw. The clinical and complementary examinations leading to the
      etiological diagnosis are described. The treatment recommended is specific to the
      structure involved and is not necessarily surgical.

PMID- 8291894
TI  - [Successful replantation of scalp avulsion in the parietal area with vascular
      microanastomosis. Apropos of a clinical case].

PMID- 8291895
TI  - Ocular malformations of Xenopus laevis exposed to nickel during embryogenesis.
AB  - The pathogenesis of eye anomalies induced by exposure to Ni2+ (as nickel
      chloride) during embryogenesis was studied in the frog, Xenopus laevis. Eyes of
      control and Ni(2+)-exposed tadpoles were examined without staining using a
      dissecting microscope, by light microscopy of histological sections, and by
      electron microscopy. The ocular abnormalities of Ni(2+)-exposed tadpoles included
      (a) microphthalmia, (b) hypopigmentation, (c) hernias and cysts of the choroid
      and retina, and (d) iris coloboma; cataracts were uncommon. The pathogenesis of
      the ocular lesions appears to involve diffuse or focal dysplasia and loss of the
      retinal pigment epithelium, with dystrophy of photoreceptor outer segments and
      protrusion of neuroretina through gaps in the pigment epithelium. This study
      confirms that Ni2+ is a potent ocular teratogen for Xenopus embryos and points to
      the retinal pigment epithelium as a primary cellular target for Ni(2+)-induced
      embryotoxicity.

PMID- 8291896
TI  - Bone marrow biopsy imprint preparations: use for molecular diagnostics in
      leukemias.
AB  - Bone marrow (BM) biopsies occasionally fail to yield aspirate specimens; such
      "dry taps" pose diagnostic difficulties. In the absence of a BM aspirate,
      morphological evaluation and cytochemistry rely on core biopsy imprint
      preparations (IP) and other analyses, e.g., molecular pathology studies, become
      impossible. The use of imprint preparations (IPs) for molecular diagnostics based
      on messenger ribonucleic acid (mRNA) analysis by reverse transcription-polymerase
      chain reaction (RT-PCR) for detection of breakpoint cluster region (bcr) gene
      rearrangements in chronic myelogenous leukemia (CML) and myeloperoxidase (MPO)
      mRNA in acute leukemias (AL) is described. Fifteen IPs from five core biopsies
      (three CML and two AL) were used. Analysis of bcr was positive in all nine IPs
      from the three cases of CML and was confirmed on peripheral blood samples.
      Detection of MPO mRNA established the myeloid lineage of the blasts in two cases
      of AL, when cytochemistry and flow cytometry failed to reveal myeloid markers.
      These tests are useful when fresh BM aspirate is unobtainable, since multiple
      imprints of the biopsy are easily prepared at the bedside.

PMID- 8291897
TI  - T-cell receptor expression in lymphoid neoplasms. A comparison of phenotypic
      expression and genotyping.
AB  - T-cell receptor antibodies (TCR alpha beta and TCR gamma delta) were used for a
      flow cytometric study of 114 specimens of lymphoid neoplasms and normal controls
      in order to find out whether or not the expression of TCR proteins differs in
      between normal and neoplastic tissues. It was found that TCR alpha beta
      population was predominant in all categories except T gamma lymphoproliferative
      disorder (TGLD), T-cell lymphoblastic leukemia (T-ALL), and natural killer-like T
      cell lymphoma (NKTL), in which three of 18, one of three, and two of two
      specimens, respectively, showed a predominant TCR gamma delta population. Natural
      killer cell lymphoma (NKL) showed essentially absence of either TCR alpha beta or
      TCR gamma delta protein. Therefore, TCR antibodies can be selectively used in
      cases of TGLD, T-ALL, and NKTL to substantiate their diagnoses. Furthermore, the
      absence of TCR protein is characteristic of NKL and helps to distinguish it from
      NKTL. Without the TCR antibodies, TCR gene analysis is sometimes needed to
      separate these two entities. When comparing with genotyping, 11 of 12 cases with
      TCR beta gene rearrangement and one of two cases with TCR alpha gene
      rearrangement expressed TCR alpha beta protein. One of four cases with TCR gamma
      gene rearrangement and both cases with TCR delta gene rearrangement expressed TCR
      gamma delta protein. Thus, TCR antibody phenotyping can reliably predict TCR
      genotypes under most circumstances.

PMID- 8291898
TI  - Comparative intestinal and testes toxicity of four aminothiols in irradiated and
      nonirradiated mice.
AB  - Intestinal and testicular toxicity in groups of nonirradiated and irradiated mice
      were investigated after intraperitoneal injection of aminothiol compounds or
      saline. Four aminothiols were studied. Three were prodrugs: WR-2721, WR-3689, and
      WR-151327 and one was the active form of WR-2721: WR-1065. Thirty minutes after
      injection, the mice were sham-irradiated or bilaterally exposed (whole body) to
      60Co gamma-irradiation at a dose rate of 1 Gy per min to a total dose of 15 Gy.
      Four days after injection, mice were euthanised, and the intestines and testes
      were removed and histologically examined. The intestinal crypt cell number was
      increased in all the irradiated mice given WR-compounds compared to controls (P <
      0.05). Interestingly, the crypt cell number in nonirradiated mice given WR-1065
      was also greater than control or WR-2721 (P < 0.05) treated mice. Germinal cell
      numbers from testes of mice administered aminothiols prior to radiation decreased
      or did not change. Some swelling of the seminiferous tubules was also observed.
      The germinal cell numbers in sham-irradiated mice were also less than the
      controls. Thus, aminothiol addition can provide limited protection to intestinal
      crypt cells but not to germinal cells of the testes in response to gamma
      irradiation. There is also evidence that aminothiols are toxic to the germinal
      cell layer of the seminiferous tubules when given to sham-irradiated mice.

PMID- 8291899
TI  - Pelvicobdominal actinomycosis associated with an intrauterine contraceptive
      device. A case of liver dissemination mimicking metastatic ovarian cancer.
AB  - A rare case of pelvicoabdominal actinomycosis with liver dissemination is
      reported in a patient with an intrauterine contraceptive device (IUCD) in place
      for 10 years. Her initial preoperative diagnosis of metastatic ovarian cancer
      emphasizes the slow indolent destructive nature of actinomycosis mimicking a
      malignancy. A history of an indwelling IUCD for several years along with a pelvic
      mass should prompt consideration of actinomycosis as a possible etiology.

PMID- 8291900
TI  - Inhibitors of 11 beta-hydroxysteroid dehydrogenase and 5 beta-steroid reductase
      in urine from patients with congestive heart failure.
AB  - Recently, the current authors reported the presence in normotensive male and
      female urines of reproducibly measurable levels of naturally occurring substances
      in partially purified extracts of urine with inhibitory activity like
      glycyrrhetic acid (GA) towards both 11 beta-hydroxysteroid dehydrogenase (11 beta
      OHSD) and steroid 5 beta-reductase (5 beta-SR) in vitro. Since these substances
      mimic two known inhibitory activities of GA, they have been named 'Glycyrrhetic
      Acid-Like Factors', abbreviated as 'GALFs' or, more specifically 11 beta-GALF for
      substance(s) active against 11 beta-OHSD, and 5 beta-GALF for those inhibitory to
      5 beta-SR. Administration of glycyrrhetic acid in man leads to cortisol-dependent
      mineralocorticoid hypertension, owing to impaired inactivation of cortisol by 11
      beta-OHSD, and may be associated with increased sensitivity to mineralocorticoids
      owing to impaired 5 beta-SR. In this preliminary report, the results are
      described of a study on the presence of GALF factors in urines collected from
      patients with congestive heart failure (CHF) and mild essential hypertension. The
      results show that in such patients there are increased amounts of both 11 beta-
      and 5 beta- GALFs compared to normotensive. The possible physiological
      significance of these results is discussed.

PMID- 8291901
TI  - Effect of chronic growth hormone administration on diabetic nephropathy in the
      rat.
AB  - Indirect data exist which implicate elevated growth hormone (GH) as a factor in
      the development of diabetic nephropathy. The administration of somatostatin
      (SRIH) has been shown to reverse many of the changes found in early diabetic
      nephropathy; however, it is unknown whether SRIH causes these effects by the
      suppression of GH or by other unspecified factors. To study directly the possible
      effect of excess GH in the development of diabetic nephropathy, either ovine
      growth hormone (0.2 mg oGH) or diluent buffer was administered IM daily for 19
      weeks to diabetic rats and to controls. Severity of nephropathy was assessed by
      24 hour urine albumin excretion (UAE), relative kidney weight, and kidney
      histology. Results showed that diabetic rats overall had elevated UAE and kidney
      weight vs non-diabetic rats (46.2 +/- 8.6 vs 5.4 +/- 1.3 mg per day and 5.7 +/-
      0.2 vs 2.7 +/- 0.1 mg per g of body weight, respectively, p < 0.001). However, no
      differences were detected between diabetic rats treated with GH compared to
      control diabetic rats. Additionally, diabetic rats had histopathologic changes
      consistent with early diabetic nephropathy, but no difference in severity scores
      was found between diabetic groups. These data provide evidence against GH as an
      etiologic factor in the development of diabetic nephropathy and it is speculated
      by the authors that SRIH exerts its protective renal effects in diabetes by
      mechanisms other than GH suppression.

PMID- 8291902
TI  - Chemical pathology of homocysteine. I. Atherogenesis.
AB  - The atherogenic properties of homocysteine were discovered by observation of
      arteriosclerosis in children with homocystinuria caused by inherited deficiency
      of three different enzymes. Hyperhomocysteinemia is generally recognized as an
      independent risk factor for coronary, cerebral, and peripheral atherosclerosis.
      Hyperhomocysteinemia is caused by heterozygosity for homocystinuria,
      micronutrient deficiency from dietary imbalance, toxins, drugs, hormones, and
      other factors, explaining many key observations concerning the epidemiology of
      atherosclerosis. The etiological factors for atherosclerosis are believed to
      increase conversion of methionine to homocysteine thiolactone, the reactive
      cyclic internal lactone of homocysteine. The free amino groups of low density
      lipoprotein (LDL) are thiolated by homocysteine thiolactone, causing aggregation
      and increased uptake of LDL by macrophages, explaining lipid deposition in
      atheromas. Homocysteine thiolactone, released from homocysteinylated LDL within
      vascular wall, promotes intimal injury, oxidation of cholesterol and unsaturated
      lipids, platelet aggregation, thrombogenic factors, myointimal hyperplasia,
      deposition of sulfated glycosaminoglycans, fibrosis and calcification of
      atherosclerotic plaques.

PMID- 8291903
TI  - [Present status of home care in oncology].

PMID- 8291904
TI  - [A case of nonresectable gastric cancer treated by sequential methotrexate and 5
      fluorouracil].
AB  - An advanced gastric cancer patient with multiple retroperitoneal lymph node
      metastases and bone metastases was treated with sequential MTX and 5-FU. Complete
      response was obtained against both gastric primary lesion and retroperitoneal
      lymph nodes observed endoscopically and by computed tomography. Partial response
      was obtained against bone metastases observed by bone scintigraphy. Side effects
      of the chemotherapy were not observed.

PMID- 8291905
TI  - [A case of Borrmann type 4 gastric cancer responding to sequential methotrexate
      and 5-fluorouracil combined with CDDP].
AB  - A case of Borrmann type 4 gastric cancer responding to sequential methotrexate
      and 5-fluorouracil combined with cis-diamminedichloroplatinum (CDDP) is reported.
      A 57-year-old woman was admitted to our hospital complaining of abdominal
      fullness. Upper gastrointestinal series and gastrofiberscopy revealed almost the
      entire stomach was involved with Borrmann type 4 cancer. Gastrectomy could not be
      performed because of peritoneal dissemination. However, the patient responded to
      sequential methotrexate and 5-fluorouracil therapy and CDDP administration. She
      enjoyed more than one year of hospital-free survival period and survived for
      almost two years.

PMID- 8291906
TI  - [A case of hepatocellular carcinoma with portal invasion and right adrenal gland
      metastasis showing marked contraction of primary tumor and metastasis with
      treated by UFT alone].
AB  - A 79-year-old female with hepatocellular carcinoma with portal invasion and right
      adrenal gland metastasis was treated by low dose UFT (200 mg/day). Two months
      after the initiation of UFT administration, CT scan revealed marked contraction
      of the primary liver tumor and right adrenal metastasis. Serum AFP and PIVKA-II
      were also reduced, and right flank pain disappeared. Six months later, CT scan
      and MRI study were performed. The findings of liver and metastatic lesion were
      the same as in the earlier study, and the liver function and the patient
      condition were well controlled. This case is probably rare, but suggestive in the
      choice of treatment for advanced hepatocellular carcinoma.

PMID- 8291907
TI  - [Effective combination therapy using radiation and a daily low dose of cis
      platinum for advanced oropharyngeal carcinoma in an elderly patient--report of a
      case].
AB  - An 83-year-old male with advanced oropharyngeal carcinoma was treated with
      combined radiotherapy and a daily low dose of cis-platinum with excellent
      results. In the early part of the treatment, radiotherapy was delivered in
      fractions of 1.8 Gy/day (5 days/week) to a cumulative dose of 20 Gy,
      concomitantly with UFT (400 mg/day po), but the response was not adequate. Then,
      instead of UFT, a single intravenous injection of cis-platinum (5 mg) was
      administered within 30 min after each radiation session without intravenous
      hydration. The total dose of cis-platinum was 140 mg and that of radiation was 70
      Gy. Moderate leukocytopenia and moderate mucositis/dermatitis were observed as
      side effects, but despite the lack of intravenous hydration no signs of renal
      toxicity were observed. Partial remission was attained by the end of the therapy,
      remnant lesions progressively diminished in size, and 4 months later all of them
      had completely disappeared on the computed tomogram. The prognosis is favorable,
      and neither recurrence nor metastasis has been found in the 14-month follow-up
      period since the lesions disappeared.

PMID- 8291908
TI  - [Essential thrombocythemia clinical characteristics and course of 10 cases].

PMID- 8291909
TI  - [Diagnosis for renal cell carcinoma].
AB  - Today's most important problems in diagnosing renal cell carcinoma are the
      methods for early detection and correct evaluation of disease stage. For early
      diagnosis, the abdominal ultrasonic diagnostic method should be used to screen
      the kidney in regional health checkups and complete medical examinations. In
      order to improve the accuracy of stage evaluation, various imaging modalities
      currently available should be used comprehensively. Chest radiography and
      abdominal CT scanning are especially effective. In detecting metastatic lesions,
      we should pay special attention to the fact that renal cell carcinomas tend to
      metastasize to the lung, liver and bone. At present, renal cell carcinoma is
      diagnosed principally by imaging, also in early diagnosis. It is desirable to
      establish tumor markers in the near future.

PMID- 8291910
TI  - [Meta-analysis of clinical trials against colorectal cancer--report of the First
      Colorectal Cancer Collaboration Meeting in Oxford].

PMID- 8291911
TI  - [Surgical treatment of renal cell carcinoma].
AB  - The concept of surgical treatment of renal cell carcinoma was discussed by
      classifying the procedures into four categories: 1) radical nephrectomy; 2)
      nephron sparing surgery such as partial nephrectomy and enucleation for small
      renal cancer detected incidentally by ultrasonography and CT; 3) extended surgery
      for cases having IVC tumor thrombus or with invasion of neighboring organs; and
      4) surgery for metastatic disease. Consequently, details of surgical procedure
      were not presented in this paper. Nephron sparing surgery and laparoscopy will be
      important steps in the future direction of surgery for renal cell carcinoma.

PMID- 8291912
TI  - [Current status of chemotherapy for renal cell carcinoma].
AB  - Renal cell carcinoma has been considered a tumor highly insensitive to
      conventional chemotherapy because of its multivariate biological potential,
      delayed manifestation of clinical symptoms and the lack of systematic
      investigation. In this respect, recent advances in pharmacological and
      pharmaceutical technology promise to be very effectively applied in chemotherapy
      for this tumor.

PMID- 8291913
TI  - [Cytokine treatment of renal cell carcinoma].
AB  - Cytokine treatment of renal cell carcinoma is described, focusing on interferons
      (IFN) and interleukin-2 (IL-2). Some cases with excellent responses are being
      reported, but long term follow-up results are rare. The results of monotherapy by
      cytokine are not satisfactory, so effective combination therapies with cytokines
      are awaited in future studies. Effects of the ongoing mono-therapy by cytokines
      are limited. For further development of the treatment, analyses of the
      complicated production system of cytokines and interactions are prerequisite.

PMID- 8291914
TI  - [Effect of adjuvant chemotherapy for patients with early gastric cancer].
AB  - Effects of adjuvant chemotherapy following curative resection were evaluated in
      patients with early gastric cancer. According to postoperative chemotherapy,
      seven hundred and thirty-one patients were divided into four groups as follows.
      MMC+FT group: those who received mitomycin C and tegafur; MMC group: those
      receiving MMC; FT group: those given tegafur or 5-FU; NC group: those who never
      received chemotherapy. Postoperative recurrence was observed in 25(3.4%) of the
      731 patients. Relationships between rates of recurrence or survival with
      clinicopathological findings were assessed among the four groups. In cases with
      cancer cell invasion of the intralesional veins, recurrence tended to occur less
      in the groups given postoperative chemotherapy, compared to the NC group. When a
      positive venous invasion was determined, rates of recurrence in the MMC+FT, MMC,
      FT and NC groups, were 7.4, 0, 0 and 35.7%, respectively. On the other hand, in
      relation to other clinicopathological findings, no differences were observed in
      rates of recurrence among those groups. As for the survival rate, no differences
      were observed in the clinicopathological findings among the four groups. These
      findings indicate that adjuvant chemotherapy may contribute to prevention of
      postoperative recurrence in patients with early gastric cancer, especially in
      cases with positive venous invasion.

PMID- 8291915
TI  - [Treatment of advanced colorectal cancer with long-term continuous infusion of 5
      fluorouracil].
AB  - The purpose of the study was to evaluate the efficacy of long-term continuous
      administration of 5-fluorouracil (5-FU) in ambulatory patients with colorectal
      cancer. Nineteen patients with advanced colorectal cancer were treated with
      continuous intravenous infusion of 5-FU (500 mg/day). The minimum duration of
      therapy was projected to be four weeks. In some patients 4 weeks interval therapy
      was selected and in other patients the duration of therapy was open-ended. A
      portable pump was used to deliver 5-FU continuously into the venous system at
      home. The pump had a subcutaneously placed port connected to a central venous
      catheter. In 19 patients, the duration of 5-FU infusion was 56 to 427 days
      (median: 139 days), and cumulative doses of 5-FU ranged from 28 to 173.5 g
      (median 69.5 g). Five patients achieved partial response (response rate: 26.3%),
      and the response lasted 80 to 339 days (median: 204 days). The fifty-percent
      survival time was 17 months. In 16 patients whose serum CEA level was elevated,
      there was a decrease to less than 50% among 11 patients (69%). Dose limiting
      toxicity was stomatitis in 4 patients and hand-foot syndrome in one, but they
      recovered after interruption of the infusion. Hematological toxicity was
      generally mild. No infusion-system related complication was encountered. Patients
      were able to be discharged and live at home during 82% of their survival period,
      while receiving this therapy. We concluded that this treatment is effective with
      tolerable toxicity and can be conducted at home.

PMID- 8291916
TI  - [Treatment of unresectable non-small cell lung cancer (NSCLC) with carboplatin
      and chronic daily administration of oral etoposide].
AB  - CBDCA has only modest activity against NSCLC, but it is less toxic than cisplatin
      (CDDP). And CB DCA has a proven synergistic effect with etoposide. On the other
      hand, etoposide is schedule dependent and when give daily peros has activity
      against several tumors. So we conducted a trial to evaluate the efficacy of a
      combination of CBDCA and chronic daily administration of oral etoposide for
      previously untreated unresectable NSCLC. The treatment schedule consisted of
      CBDCA 400 mg/m2 on day 1 and chronic daily administration of oral etoposide of 50
      mg/day/body for 21 consecutive days every 28 days. Twenty-nine of 36 enrolled
      patients were eligible. The response rate was 27.6% (95% confidence interval:
      11.1-43.9%). The median survival time was 405 days. The primary toxicity was
      myelosuppression: leukopenia, neutropenia, anemia and thrombocytopenia of Grade 3
      or 4 were 14.7%, 29.4%, 26.5%, and 5.9%, respectively. No bleeding episodes or
      toxic death were observed. Nonhematologic toxicity was slight, and there was no
      severe gastrointestinal toxicity. This combination was effective against NSCLC
      with tolerable toxicity and an "easily tolerated outpatient regimen".

PMID- 8291917
TI  - [MEP (methotrexate, etoposide and cisplatin) and M-VAC (methotrexate,
      vinblastine, doxorubicin and cisplatin) for advanced uroepithelial cancer--a
      preliminary report of MEP as second line chemotherapy for recurrence after M
      VAC].
AB  - Combination chemotherapy with methotrexate, vinblastine, doxorubicin and
      cisplatin (M-VAC regimen) or with methotrexate, etoposide and cisplatin (MEP
      regimen) was administered to 32 patients with advanced measurable uroepithelial
      cancers. Fifteen patients among them were adequately treated with M-VAC regimen,
      and 11 with MEP regimen. Complete remission was not achieved clinically in any
      patients. Partial remission occurred in 73.3% (11/15) of M-VAC patients and 72.7%
      (8/11) of MEP patients. Of eleven MEP patients, six were treated with MEP therapy
      as second line chemotherapy for the recurrence after other chemotherapy (5 cases
      after M-VAC, 1 case after intraarterial cisplatin). They showed a considerable
      response (4 patients, PR; 2 patients, MR) and an appreciable remission period,
      not inferior to those of first line chemotherapy with M-VAC regimen. The present
      study shows that MEP may be a promising regimen for advanced uroepithelial
      cancers, especially as a second line chemotherapy for relapsed cases after M-VAC
      therapy.

PMID- 8291918
TI  - [An early phase II study of CPT-11 (irinotecan hydrochloride) in patients with
      hematological malignancies].
AB  - An early phase II study of CPT-11 (irinotecan hydrochloride) was conducted in
      patients with hematological malignancies by 4 administration regimens in a
      cooperative study involving 13 institutes in Japan. The overall response rate was
      23% (7/30) for non-Hodgkin's lymphoma, 33% (1/3) for Hodgkin's disease, 18%
      (2/11) for acute lymphoblastic leukemia and 7% (1/15) for acute myelogenous
      leukemia. One PR was also obtained in a patient with chronic myelogenous
      leukemia. Among responders, 6 relapsed and refractory malignant lymphomas (ML)
      and 2 relapsed and refractory acute leukemias (AL) were involved. The response
      rates in ML with the regimens B (40 mg/m2 for 5 days every 3-4 weeks) and C (40
      mg/m2 for 3 days every weeks) were 31% (5/16) and 33% (3/9), respectively. The
      other regimens (regimen A, 200 mg/m2 once a day every 3-4 weeks and regimen D)
      resulted in no response. Responses in AL were only observed in regimen D (20
      mg/m2 twice a day for 7 days every 3-4 weeks). Major toxicities were leukopenia
      (91%), nausea/vomiting (74%), diarrhea (73%) and anorexia (64%). The incidence of
      severe gastrointestinal symptoms was higher in regimen B than regimen C. Further
      studies are warranted to confirm the effectiveness and safety of CPT-11 against
      ML and AL. The recommended administration schedule was regimen C for ML and
      regimen D for AL.

PMID- 8291919
TI  - [An early phase II study of CPT-11 (irinotecan hydrochloride) in patients with
      advanced breast cancer].
AB  - An early phase II study of irinotecan (CPT-11) in patients with advanced or
      recurrent breast cancer was undertaken by a cooperative study group of 15
      institutes in Japan. CPT-11 was administered by intravenous drip-infusion. The
      administration schedules were 100 mg/m2 weekly (regimen A), 150 mg/m2 biweekly
      (regimen B), and 200 mg/m2 every 3-4 weeks (regimen C). There were 4 partial
      responses (PRs), 12 cases with no changes (1 minor response) and 9 cases of
      progressive diseases with a response rate of 16% (4/25). One out of 7 patients on
      regimen A and 3 patients out of 15 patients on regimen C achieved PR with a
      response rate of 14% and 20%, respectively. In three out of 4 PRs, prior
      chemotherapy, endocrinotherapy or radiotherapy had failed. Major adverse
      reactions were leukopenia 28/33 (85%), neutropenia 19/25 (76%), anemia 15/33
      (46%), nausea/vomiting 28/33 (85%), anorexia 25/33 (76%), diarrhea 22/33 (67%)
      and alopecia 20/33 (61%). The incidence of leukopenia and thrombocytopenia seemed
      to be higher in regimen C than regimen A, and diarrhea was also more severe in
      regimen C than regimen A. The recovery of leukopenia was delayed in some patients
      on regimen C. The results suggested that CPT-11 was effective against advanced or
      recurrent breast cancer. The recommended administration schedule for a late phase
      II study was thought to be 100 mg/m2 weekly, considering efficacy and safety.

PMID- 8291921
TI  - [A pharmacokinetic study on high-dose methotrexate administration--the effects of
      volume changes of parenteral solutions on the elimination rate].
AB  - Methotrexate (MTX) serum concentrations were measured in 7 cases (2 patients) in
      which a high-dose administration of MTX with citrovorum factor rescue for
      osteogenic sarcoma were performed for repressing activity in the original lesion
      and satellite micrometastasis. In the pharmacokinetic analysis, the changes of
      MTX serum concentrations were explained by a 2-compartment open model under the
      assumption that the elimination rate was proportional to both of volume of
      parenteral solution and the amount of water intake. It was suggested that MTX
      serum concentration could be controlled by adjusting the volumes of parenteral
      solutions. MTX amount in the peripheral compartment was found about ten times
      larger than that in the central compartment after about 40 h of administration.
      It is considered that an early increase in the volumes of parenteral solutions is
      effective to keep the safety level of MTX serum concentration, and continuous
      infusion is important for avoiding the severe side effects caused by delayed
      elimination of MTX.

PMID- 8291920
TI  - [Comparative trial of granisetron versus granisetron plus methylprednisolone for
      the prevention of nausea and vomiting induced by cancer chemotherapy].
AB  - Preclinical and clinical studies have demonstrated the effectiveness of
      granisetron in preventing emesis induced by antineoplastic chemotherapy. This
      comparative study was undertaken to investigate the efficacy and safety of
      granisetron (40 micrograms/kg) and granisetron plus methylprednisolone (MPL; 10
      mg/kg). Sixty-eight patients were given granisetron 170 times and thirty-nine
      patients were given a combination of granisetron and MPL 81 times. Sixty-one
      patients received the treatment in crossover fashion during the same chemotherapy
      regimens. The emetic and nausea episodes were counted during the 24 hours
      following each chemotherapy treatment. Complete response, no emesis or less than
      two episodes, were obtained in 75.3% (128/170 times) of patients receiving
      granisetron alone compared to 85.2% (69/81 times) of patients receiving the
      combination of granisetron plus MPL. There were no significant differences in
      complete responses between the two groups, male and female, and each age group.
      However, 11 of eighteen patients receiving granisetron alone who responded
      mildly, if at all, with respect to nausea and vomiting, showed a complete or
      major response when MPL was added to granisetron. There were two patients who
      developed temporal paresthesia of the both hands as an adverse effect, but there
      was spontaneous recovery after 3 hours. Our data suggested that granisetron plus
      MPL was slightly more effective than granisetron alone and a safe antiemetic
      drug.

PMID- 8291922
TI  - [Nuclear cardiology].

PMID- 8291923
TI  - [The treatment of arterial hypertension in the patient with an acute
      cerebrovascular event].

PMID- 8291924
TI  - [Peripheral and coronary angioscopy: its correlation with endovascular
      procedures].
AB  - The efficacy of any method of transluminal angioplasty has been evaluated with
      angiography, this can show the major anatomic results. Angioscopy can detect by
      direct observation, the induced changes in the vessel wall morphology after the
      recanalization method. We studied 5 coronary arteries and 9 peripheral arteries
      with total occlusion in 7, and the other 7 with more than 75% of obstruction. All
      of them were evaluated with angiography and angioscopy, before and after the
      transluminal angioplasty. Eleven of the arteries were treated by transluminal
      ultrasound angioplasty, we obtained recanalization in 90% of them, in 6 (55%) of
      this we found angioscopic evidence of dissection in variable degrees. Two cases
      were treated only with balloon angioplasty, and the angioscopy image was of
      dissection too. In the only case of laser angioplasty we observed dark brown
      coloration in the treated lesion suggesting carbonization changes. The initial
      angiography analysis did not suggest the presence of complication of the atheroma
      plaque. However in 21% of the cases the angioscopy inspection demonstrated and
      hemorrhagic dye of the endothelium, and thrombosis in situ in 29%. We no found
      correlation in angiography and angioscopy aspect in 25% of the cases. Some of the
      endothelial alterations that can not be detectable by angiography, can be
      demonstrated by angioscopy, this changes could improve the appreciation of any
      recanalization method results, that could suggest its possible immediate and late
      complications.

PMID- 8291925
TI  - [Pericardiectomy: a challenge, a reality. The surgical experience of the
      Instituto Nacional de Cardiologia "Ignacio Chavez"].
AB  - The surgical aspect of the pericardial disease has grown in the last years due to
      new diagnostic, surgical and anesthetic procedures. We reviewed 20 patients, who
      underwent pericardiectomy in the National Institute of Cardiology "Ignacio
      Chavez" between august 1987 and september 1992. Nine males and eleven females
      whose age ranged from 18 years to 57 years with a mean of 35.8 years. We found as
      causes of pericardial disease: 5 patients with recurrent pericardial effusion, 4
      constrictive pericarditis, 2 cases with uremic pericarditis, 2 cases of
      "postpericardiotomy syndrome" 2 cases of infectious origin, idiopathic causes in
      two, others less frequent causes were neoplastic pericarditis in one, post
      traumatic in one and secondary to radiotherapy in another one. The diagnosis was
      made by clinical findings, chest X rays, echocardiography and cardiac
      catheterization. A medial sternotomy was made in all patients, and the
      pericardium resection was made toward the anterior aspect of the phrenic nerve.
      In all the patients operative monitoring included central venous catheter and
      radial indwelling catheter, Swan Ganz catheter in 12 cases (60%) and
      cardiopulmonary bypass available. One death was reported in an uremic patient,
      secondary to low cardiac output and multiple organic failure. One year mortality
      increased to 10% with the inclusion of a rhabdomyosarcoma. Surgical complications
      included two cases (10%) with supraventricular arrhythmias, one case (5%)
      incomplete right bundle branch block, postoperative bleeding one (5%) and other
      one (5%) postoperative mediastinitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291926
TI  - [Calcified embolism of the coronary artery due to the degeneration of a
      bioprosthesis in the aortic position].
AB  - We present a case of arterial coronary embolism by calcified material of a
      bioprosthesis of bovine pericardium of the INC in aortic position 8 years after
      its implantation. Echocardiogram and catheterization with coronarography
      demonstrated prosthetic aortic dysfunction and normal coronaries. The patient
      complained of stable angor and dyspnea. During coronarography there was an
      increase of symptoms together with ECG changes and after a few hours with
      enzymatic increase. The patient was brought urgently to surgery where mitroaortic
      prosthesis was changed with mechanic prosthesis. As surgical findings: absence of
      a leaflet of prosthesis in aortic position with free fragmented calcium in
      periannular region and two remaining leaflet completely calcified, prosthesis in
      mitral position of normal appearance. We conclude that ischemia or myocardial
      infarction in presence of normal coronaries in patients with bovine pericardial
      bioprosthesis in aortic position can be secondary to calcium embolism, originated
      by mineralization process of a degenerated bioprosthesis several years after its
      implantation.

PMID- 8291927
TI  - [The versatility of anterograde/retrograde cardioplegia in heart surgery].
AB  - Eighty patients underwent open-heart surgery from March 1990 to March 1993. We
      used combined aortic root (antegrade)/coronary sinus (retrograde) perfusion for
      cardioplegia delivery as a means of myocardial protection. The special
      retroplegia cannula was introduced to the coronary sinus (CS) in 67 patients by
      the transatrial (blind intubation) after one cannula cava insertion; the CS was
      cannulated under direct vision by right atriotomy after bicaval cannulation in 13
      patients. Varied and prolonged cardiac procedures were done using cooled
      crystalloid cardioplegia (4 centigrades + potassium) except in one patient with
      severe ventricular damage in whom warm blood cardioplegia was infused. There was
      no CS or cardiac vein damage or disruption. There was no A-V blockade. The CS was
      intubated easily in all cases and cardioplegia solution readily infused. Coronary
      sinus pressure never exceeded 40 mm Hg. Overall hospital mortality (30 days
      postoperative) was 3.75% (3 cases). Sepsis was the cause of death in 2 patients
      and stroke in one. Inotropes were used in few cases as a means of renal
      protection. We conclude that the combined antegrade/retrograde cardioplegia
      delivery can be used routinely in most patients undergoing open-heart surgery.

PMID- 8291928
TI  - [Ventricular diastolic function: a correlation between phonomechanocardiography
      and echo-Doppler].
AB  - With the purpose to compare phonomechanocardiography and echo Doppler in the
      assessment of diastolic function of the left ventricle, we study 45 patients (30
      male and 15 female) average age 50 +/- 9 years. We performed
      phonomechanocardiogram, echo-M, 2-D and Doppler transmitral. They were classified
      in four group according to mitral flow pattern: normal 14 patients; pattern I by
      Appleton (PI) 14 patients, 11 with aortic stenosis and 3 with hypertrophic
      cardiomyopathy; pattern II (PII) 12 patients with dilated cardiomyopathy grade
      III-IV and the last group of 5 patients with myocardial infarction with normal
      mitral flow but with impaired diastolic function by phonomechanocardiography. The
      phonomechanocardiographic index of ventricular relaxation (A2-O, ITRAT),
      compliance (a/D) and global diastolic function (ITAD) correlated with Doppler
      index (A2-D, E/A, atrial filling fraction, E-F slope and deceleration time) in N
      + PI group. The correlation was not significant when N + PI + PII or PI + PII
      groups were considered. The ITAD and E/A had r = 0.713 (p < 0.001) in N + PI, r =
      0.12 (NS) in N + PI + PII and r = -0.308 (NS) in PI + PII. There was a
      dissociation between increased "a" wave in apexcardiogram and little "A" wave in
      PII patients suggesting "atrial failure". The patients with myocardial infarction
      received isosorbide dinitrate 5 mg showing changes of "pseudonormalizated"
      pattern in PI with normalized ITAD. This findings suggest that assessment of
      diastolic function by Doppler is dependent of loading conditions (specially
      preload), and cannot evaluate relaxation in PII but this is possible by
      phonomechanocardiography. It is advised the combination of the two technics for
      better assessment of diastolic function.

PMID- 8291929
TI  - [Arterial hypertension and other coronary risk factors in primary care].
AB  - This paper is about the effort to measure the assistance load at the first level
      of attention given by arterial hypertension and care risk factors. It is been
      worked as a demonstration project to initiate activities within the setting of a
      Health Center. The risk factors are explored from the proportions of patients
      with the problems of obesity, smoking, hyperlipidemia, diabetes mellitus and
      alcoholism. The information was obtained from 395 consecutive cases out of 1100
      persons who came to the center in a month period. They were 325 women (82.2%) and
      70 men (17.2%) with a range of 18 to 85 years, average 40 +/- 17 and a median of
      36. Obesity was encountered in 35.7% in men and 48.8% in women. Diabetes was
      found in 9.1% both sexes. Hypercholesterolemia > 200 mg/dl in 30.4% and > 240
      mg/dl in 19.6%. Alcohol abuse was encountered in 14%, 9.2% in women and 37.7% in
      men. Smoking was present in 22.3% of them, 16.3% in women and 50% in men. High
      blood pressure > 140/90 mm Hg or hypertension history was present in 21% of the
      cases. Controlled cases were 6.6%. In the whole group 34% showed at least one
      risk factor, 57% showed two factors and 66% showed three factors. Therefore, the
      best estimate of assistance load, on the fight of risk factors associated to
      hypertension should not consider less than 70% among the regular subjects coming
      to this health center.

PMID- 8291931
TI  - [The cardiovascular effects of serotonin receptor agonists and antagonists (I)].

PMID- 8291930
TI  - [The correlation of atrial natriuretic peptide values with those of renin,
      angiotensin and aldosterone in hypertension patients below and above 50].
AB  - A comparison of ANP and RAA. In 6 healthy subjects < 50 y, 5 healthy subjects >
      50 y, 44 patients with essential hypertension < 50 y, and 41 patients with
      essential hypertension > 50 y, was performed. ANP values in healthy subjects < 50
      y, were means = 44 +/- 7 PG/ml, and means = 87.33 +/- 14 PG/ml in those > 50 y.
      (P < 0.01). 80% of hypertensives < 50 y, had normal values of ANP (means = 63.8
      +/- 10 PG/ml) and 20% high values (means = 131 +/- 6 PG/ml) (P < 0.001). 70% of
      hypertensives > 50 y, had high ANP values (means = 260 +/- 114 PG/ml) and 30%
      normal values (means = 75 +/- 5 PG/ml) (P < 0.001). Values for RAA were low or
      normal in 96% of cases with high ANP values (P < 0.001), and 100% of the cases
      with high RAA values, had low or normal ANP values. (P < 0.0001). This
      correlation had an statistically significant value for groups over 50 years (high
      ANP values, low RAA values) (P < 0.001) and high RAA values with low or normal
      ANP values in groups below 50 y (P < 0.001). We observed no significant
      correlation between ANP values and LVH. According to our results, essential
      hypertensives < 50 y, have low or normal ANP values in the majority of cases (P <
      0.001). Essential hypertensives over 50 y. Have high ANP values also in the
      majority of cases (P < 0.001). As previously reported, an inversely proportional
      ratio between RAA and ANP was found in our study. The significance of ANP in
      regulating blood pressure in the elderly is considered.

PMID- 8291932
TI  - [Syncope].

PMID- 8291933
TI  - [Re-evaluating the noninvasive reperfusion criteria in patients with AMI
      undergoing pharmacological thrombolysis (I)].

PMID- 8291934
TI  - [Neurohormonal profile in aortic valve stenosis].
AB  - The authors studied the responses of the main systems of sympathetic and hormonal
      regulation in valvular aortic stenosis, a special model of dissociation between
      arterial pressure and left ventricular function. The series comprised 14 patients
      with an average age of 70 +/- 9 years without diuretic therapy presenting with
      pure calcific aortic stenosis without other valvular or coronary disease. All
      were in sinus rhythm; 5 were taking an angiotensin converting enzyme inhibitor.
      Plasma concentrations of endothelin 1, atrial natriuretic factor (ANF), arginine
      vasopressin (AVP), catecholamines, plasma renin activity (PRA), angiotensin II
      and aldosterone were measured in resting, fasting patients, by blood samplings
      from a peripheral vein immediately before cardiac catheterisation. The results
      were compared with the severity of the aortic stenosis (aortic valve area greater
      or less than 0.7 cm2), the ratio of left ventricular work/myocardial mass
      (greater or less than 0.6) and treatment (with or without ACE inhibitors).
      Catecholamine levels were much higher in severe aortic stenosis (noradrenaline:
      579 +/- 66 pg/ml when valve surface area > 0.7 cm2 versus 900 +/- 92 pg/ml when
      valve surface area < 0.7 cm2; p < 0.01). Endothelin -1 and AVP concentrations
      were normal. Whereas PRA was normal, aldosterone levels were increased in
      patients without treatment by ACE inhibitors. This treatment did not, however,
      normalise the noradrenaline levels. The increase in ANF concentration was large
      when left ventricular work decreased with respect to myocardial mass (190.8 +/-
      42.3 pg/ml if W/M was decreased versus 82.7 +/- 15.4 pg/ml when W/M was normal):
      this could be related to the degree of left ventricular hypertrophy.

PMID- 8291935
TI  - [Technetium TC 99m pyrophosphate myocardial scintigraphy in amyloidosis.
      Correlations with Doppler echocardiography].
AB  - Technetium 99m cardiac scintigraphy as practiced at present for diagnosing
      amyloisodid only provides a visual semi-quantitative assessment of uptake of the
      isotope. To improve the diagnostic accuracy of the method, the authors evaluated
      prospectively a personal technique of scintigraphy quantification based on early
      images obtained at the 20th minute in 15 patients with neuropathic amyloidosis.
      Doppler echocardiographic studies indicated that 9 patients had cardiac
      involvement whilst 6 were free of cardiac amyloidosis. The index of isotopic
      uptake (ratio of cardiac/abdominal uptake) was 0.44 to 1.58 in the first group
      and 0.09 to 0.31 in the second group. The correlation between the scintigraphic
      index and interventricular septal or posterior wall thickness measured by
      echocardiography was poor. These results obtained in 15 patients with neuropathic
      amyloidosis suggest that the scintigraphic index measured at the 20th minute is
      discriminatory and allows identification of those patients with cardiac
      involvement. On the other hand, the correlations with echocardiographic wall
      thickness are poor. Technetium 99m cardiac scintigraphy with this technique of
      quantification is a useful tool for diagnosing cardiac amyloidosis, especially
      when echocardiography is difficult to interpret.

PMID- 8291936
TI  - [Value and limits of single-plane transesophageal echocardiography in
      dysfunctions of aortic valve prosthesis].
AB  - The authors reviewed retrospectively the results of transoesophageal and
      transthoracic echocardiography in 26 patients with prosthetic aortic valve
      dysfunction in order to study the value and limitations of monoplane
      transoesophageal echocardiography in this condition. Surgical data was available
      in 14 of these cases. The diagnosis of abscess of the aortic ring was made on 7
      occasions by transoesophageal echocardiography and on 3 occasions by
      transthoracic echocardiography Bacterial vegetations were visualised in 5 cases
      by transoesophageal echocardiography and in 1 case by transthoracic
      echocardiography. The diagnosis of thrombosis was made in 1 case by
      transoesophageal echocardiography and missed by transthoracic echocardiography;
      fibrous pannus (n = 1) was not recognised on transoesophageal and transthoracic
      echocardiography. In the latter two conditions, transthoracic Doppler showed
      signs of obstruction. The diagnosis of a stenotic bioprosthesis due to
      fibrocalcific degeneration was made in 1 case by transoesophageal and in 1 case
      by transthoracic echocardiography. Prolapse of cusp was diagnosed in 6 cases by
      transthoracic echocardiography. An intraprosthetic valve leak was visualised in 7
      cases by transoesophageal echocardiography and in 9 cases by transthoracic
      echocardiography; periprosthetic leaks were diagnosed in 9 cases by
      transoesophageal and in 12 cases by transthoracic echocardiography. These results
      indicate that transoesophageal echocardiography is a major advance in the
      diagnosis of abscess of the aortic ring, bacterial vegetations and prosthetic
      valve thrombosis. On the other hand, transthoracic echocardiography remains
      superior for the quantification or regurgitation and enables evaluation of
      transprosthetic gradients of obstructive prostheses with continuous mode Doppler.
      Therefore, the two methods are complementary.

PMID- 8291937
TI  - [Mid-term clinical and prognostic evaluation of idiopathic atrial fibrillation].
AB  - Forty-six patients with idiopathic or lone atrial fibrillation (AF) underwent
      clinical evaluation in the cardiology outpatient department. The follow-up period
      was 4.6 +/- 2.5 years. The prevalence of idiopathic AF was 19% (89% paroxysmal
      and 11% permanent) in a population of 244 patients with atrial fibrillation. The
      global prevalence was 1.15% out of 4,000 patients examined over the same period.
      A history of paroxysmal atrial fibrillation over a 6 +/- 4 year period was
      obtained in 61% of the patients with idiopathic AF before the study. At
      inclusion, 24% of patients were asymptomatic. During follow-up, 12 patients (26%)
      developed cardiovascular disease and/or hypertension. The size of the left atrium
      was measured by echocardiography in 45 patients and reevaluated in 30 of them
      during follow-up without any statistically significant difference being observed
      between the two values. There were no thromboembolic complications or deaths
      during follow-up. These results show that idiopathic AF is not uncommon in
      cardiology clinics. The evolution of the paroxysmal forms is variable--but the
      medium-term prognosis is excellent. In some cases, idiopathic AF may be a
      manifestation of asymptomatic coronary artery disease but the relationship
      between the two pathologies has not been definitely established.

PMID- 8291938
TI  - [Value of protocol using standardised activities of daily living for the
      programming of rate responsive pacing].
AB  - To optimise the regulation of rate responsive pacemakers, the authors propose
      standardized tests of everyday activities. Seven tests were selected with
      monitoring of the heart rate (HR) by telemetry every 30 seconds: two reference
      tests--cycloergometry: 2 steps of 3 minutes at 30 then 60 watts and a symptoms
      limited Bruce protocol on the treadmill--and 5 everyday activities, walking,
      going upstairs, going downstairs, squats and hyperventilation. Fifteen normal
      subjects (65 +/- 10 years) were used to establish normal values and 10 patients
      implanted with a Telelctronics Meta DDDR 1250 rate responsive pacemaker with
      minute ventilation sensing, were studied after choice of minimal and maximal HR
      on clinical criteria (age, pathology). The rate response frequency (RRF) was
      adjusted so that the pacemaker HR was within normal values. At the beginning of
      each test, the sensor was hypokinetic (p = 0.01). Hyperventilation caused
      hyperkinesia of the sensor (p = 0.01). A good correlation was obtained between PM
      patients and normal subjects on walking, going up down stairs and for squats (p =
      NS). On cycle ergometry and treadmill, the PM remained slightly hypokinetic (p =
      0.02). The study of "ideal" RRF measured at "peak exercise" as proposed by the
      manufacturer was only satisfactory in 1 of the 10 cases. This study confirms the
      value of using everyday activities for programming rate responsive pacemakers,
      the limitations of automatic adjustment and the need for personalized
      programming.

PMID- 8291939
TI  - [Mobile thrombus of the right heart and pulmonary embolism: diagnostic and
      therapeutic problems. Apropos of 12 cases].
AB  - The objectives of this report were to analyse clinical presentation,
      echocardiographic features and diagnostic and therapeutic problems posed by an
      unusual form of thrombo-embolic disease: mobile right heart thrombosis.
      Systematic echocardiography in 170 cases of severe pulmonary embolism identified
      mobile right thrombi in 12 cases. The auscultatory findings were abnormal in 6
      cases, 3 showing signs of tricuspid obstruction. Two-dimensional echocardiography
      showed an extremely mobile right atrial mass, sometimes prolapsing across the
      tricuspid valve, which was variously spheric, ovoid or worm-like; dilatation of
      the right heart chambers and echocardiographic signs of cor pulmonale were
      observed in all cases. The differential diagnosis with other embolic masses of
      the right atrium and, above all, with well-developed Chiari networks, may be
      difficult and requires transoesophageal echocardiography. Pulmonary angiography
      is contra-indicated because of the risk of embolism. Embolectomy under
      cardiopulmonary bypass was carried out in 8 patients, immediately after
      echocardiography in 6 cases. The thrombus was recovered from the right atrium in
      6 cases and from the pulmonary artery in 2 cases: there was one operative death.
      Medical treatment was administered to 3 inoperable patients. The clinical and
      echocardiographic outcome was good in 2 of these but the third patient died;
      autopsy revealed thrombi in the right atrium and pulmonary artery. One patient
      died before any treatment could be given and autopsy showed the thrombus in the
      pulmonary artery. These results confirm the extreme instability of this type of
      thrombus and the risk of death due to its embolism.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8291940
TI  - [Variations in blood lipid levels in adolescents: relation to changes in
      lifestyle. A longitudinal approach].
AB  - In order to assess the relationship between changes in life style (taking up
      smoking, giving up sporting activity) and plasma lipids, 3,650 young subjects
      aged 14 to 18 years, from the Lorraine region, were examined on two occasions
      separated by a 5 year interval. At the second examination, 39% of the boys and
      33.8% of the girls had taken up smoking, and 52% of the boys and 68% of the girls
      had given up strenuous physical activity. These changes in life style were
      associated with a significant change in total cholesterol in boys and also of
      triglycerides after adjustment of values for age and variation in body mass:
      starting smoking or the giving up of sporting activities was associated with a
      greater increase in cholesterol and triglyceride levels. These results underline
      need for increasing efforts in the prevention of cardiovascular disease in young
      subjects, and emphasise the importance of maintaining physical activity and of
      not smoking.

PMID- 8291941
TI  - [Electrophysiological properties of the transplanted heart. Clinical
      applications].
AB  - With the improvement in the results of cardiac transplantation, more and more
      cardiologists are called on to follow up cardiac transplant patients.
      Cardiological follow-up requires a knowledge of the electrocardiographic and
      electrophysiological features of the transplanted heart after surgery and the
      suppression of autonomic innervation. The transplanted heart ECG is characterised
      by the presence of 2 P waves of different morphology and frequency (from the
      native and transplanted atria), an acceleration of the sinus rhythm, clockwise
      rotation of the longitudinal axis, right bundle branch block and ST-T segment
      changes. The increase in heart rate during exercise is catecholamine-dependent,
      more progressive and less important than in normal subjects, as is the
      deceleration of the cardiac rhythm when exercise is stopped. The observation of
      early sinus node dysfunction is not rare (6.6%) and though usually asymptomatic
      and transient, implantation of a pacemaker is commonly proposed with different
      modes of stimulation (VVI, VVIR, AAIR, AAT). The authors have observed changes in
      the electrophysiological properties of experimental transplanted hearts during
      acute rejection. The most important of these were in the conduction of the
      activation within the atrium and in the atrioventricular node, and a reduction in
      the amplitude of the ventricular potential. The recording of these changes in
      humans by a non-invasive method could help early diagnosis of acute rejection and
      limit the number of endomyocardial biopsies. Of the non-invasive techniques under
      assessment, signal-averaged electrocardiography (temporal and/or frequency
      analysis) seems to be the most promising.

PMID- 8291942
TI  - [Implantation of an endoprosthesis for the repair of stenosis of valved tube
      between right ventricle and pulmonary artery].
AB  - The author report the case of a 35 year old man who had undergone a Rastelli
      procedure in 1976 for transposition of the great arteries and who required
      indertion of a stent for stenosis of the valved right ventricular-pulmonary
      artery conduit. The patient presented with florid signs of right ventricular
      failure due to degenerescence of the conduit which had a 60 mmHg pressure
      gradient between the right ventricle and the pulmonary artery. This palliative
      procedure was decided upon given the high risk of reoperation. The valved conduit
      was dilated with a balloon catheter before insertion of a Gianturco stent (30 mm
      diameter and 50 mm long) to cover both conduit and the valvular apparatus. The
      insertion of the stent was easy with immediate normal expansion and the procedure
      was well tolerated. After insertion of the stent, the right ventricular-pulmonary
      artery pressure gradient fell from 60 to 35 mmHg. Angiographic control one month
      later showed a sustained hemodynamic result with a perfectly patent stent. The
      patient was pauci-symptomatic when reviewed six months after the procedure.

PMID- 8291943
TI  - [Echocardiographic diagnosis of a thrombus trapped in a patent foramen ovale.
      Apropos of a case].
AB  - The authors report the case of a patient presenting with pulmonary embolism in
      which transthoracic echocardiography showed the presence of an intracardiac
      thrombus trapped in a patent foramen ovale; this was confirmed at surgery. It is
      rare to see this type of thrombus (which usually gives rise to paradoxical
      embolism) by transthoracic echocardiography. Previously, this used to be a
      postmortem diagnosis but the condition is often suspected nowadays when deep
      venous thrombosis and/or pulmonary embolism, an unexplained systemic embolism and
      a right-to-left interatrial shunt, are associated. However, the diagnosis can
      only be confirmed by the visualisation of the thrombus crossing the interatrial
      septum.

PMID- 8291944
TI  - [Left pulmonary artery originating from the ascending aorta in tetralogy of
      Fallot. Therapeutic strategy].
AB  - The authors report the rare case of a 12 year old child with an anomalous origin
      of the left pulmonary artery from the ascending aorta associated with Tetralogy
      of Fallot. This complex congenital malformation was treated surgically by a
      Deleval anastanosis between the right subclavian and right pulmonary arteries.
      The result was good with a 9 year follow-up, the patient having only Grade II
      effort duspnoea and cyanosis. The authors discuss the advantages and drawbacks of
      the different possible surgical approaches to this problem in the light of the
      outcome of this case and a review of the literature.

PMID- 8291945
TI  - [Instantaneous pressure-velocity relationship of the coronary flow, alternative
      to coronary reserve measurement: a feasibility study and reproducibility of the
      method].
AB  - Animal experimentation has shown that the instantaneous pressure-velocity of
      coronary blood flow in the hyperaemic phase has a linear relationship. The slope
      of this regression evaluates coronary reserve independently of haemodynamic
      variables and the X-intercept (zero flow pressure or Pf = 0) determines the intra
      myocardial back pressure which could influence the regulation of coronary flow.
      The object of this study was to evaluate the instantaneous pressure-velocity
      relationship of coronary flow in clinical practice and to analyse the
      reproducibility of this parameter. Forty-nine patients were divided into two
      groups, depending on whether their coronary arteries were angiographically normal
      (n = 34) or atheromatous with stenosis > or = 35% of the reference diameter (n =
      15). Recordings of coronary flow velocity were made with a Doppler transducer
      mounted on a 0.018 inch guide wire. The slope of the diastolic linear segment of
      the pressure-velocity relationship was determined at the peak of papaverine
      induced vasodilation from 4 consecutive cycles by a regression analysis. The
      pressure value at 0 flow was obtained by extrapolation of the regression slope to
      the axis of aortic perfusion pressure. A good quality spectral recording allowing
      reliable analysis of the velocity profile was obtained in 88% of cases (44/49).
      The high values of the correlation coefficient observed with each measurement of
      the slope confirm the applicability of linear regression analysis to the pressure
      velocity relationship. The slope of the pressure-velocity relationship was
      significantly lower in patients with coronary stenosis (1.7 +/- 0.7 cm/s/mmHg in
      normal vessels versus 0.7 +/- 0.3 cm/s/mmHg in stenotic arteries, p < 10(-4)),
      and, similarly, the pressure at zero flow was also reduced (36.9 +/- 16 mmHg
      versus 25.5 +/- 12 mmHg, p = 0.03). A statistically significant correlation was
      observed between the slope values and coronary flow reserve but no correlation
      was demonstrated between the slope and intraluminal surface area of
      angiographically normal coronary arteries or the slope and degree of stenosis of
      atheromatous vessels. The linear regression slope and the pressure at zero flow
      were lower when the pressure-velocity relationship was measured during long
      diastolic periods induced by the injection of adenosine. In addition, the
      curvilinear appearances of the pressure-velocity relationship observed during
      these long periods suggest that the linear regression model is not applicable
      throughout the whole range of pressures and velocities, especially for the lowest
      values.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8291946
TI  - [Obstructive hypertrophic cardiomyopathy: medical or surgical treatment?].
AB  - This retrospective study assesses the results of medical and surgical treatment
      on survival and functional capacity of patients with hypertrophic obstructive
      cardiomyopathy (HOCM). Between 1981 and 1991, 73 patients were referred for
      treatment of HOCM: 24 were operated (Group 1) and 49 were treated medically
      (Group 2). Patients in Group 1 had more severe forms of HOCM than those in Group
      2: 83% were in > or = NYHA Class III compared with only 20% in Group 2 (p =
      0.003); 42% had previous cardiac failure compared with 16% in Group 2 (p = 0.02);
      29% had atrial fibrillation compared with only 8% in Group 2 (p = 0.004); the
      average intraventricular pressure gradient was 78 mmHg compared with 42 mmHg in
      Group 2 (p = 0.001); mean pulmonary arterial pressures were 24 mmHg compared with
      15 mmHg in Group 2 (p < 0.001); the cardiac index was 2.2 l/min/m2 compared with
      2.7 l/min/m2 in Group 2 (p = 0.001); Sellers > or = grade 3 mitral regurgitation
      was present in 48% compared with 12% in Group 2 (p = 0.002). However, a family
      history of HOCM or of sudden death was commoner in Group 2 (28% vs 4% in Group 1:
      p = 0.03). Surgery consisted of myomectomy alone (5 patients) or associated with
      mitral valve replacement (MVR) (17 patients) or MVR alone (2 patients). Two
      patients in Group 1 died (1 perioperative death, 1 late death due to dissection
      of the aorta), giving over a 3.4 +/- 3.0 year follow-up period without any losses
      to follow-up, an abnormal mortality of 2.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291947
TI  - [Percutaneous mitral commissurotomy during pregnancy].
AB  - This report analyses the efficacy and tolerance of percutaneous mitral
      commissurotomy (PMC) in 10 pregnant women with severe mitral stenosis. Pregnancy
      was the cause of decompensation of the mitral stenosis and surgery was not
      considered because of the foetal risk. PMC was undertaken after an average of 26
      +/- 4 weeks of gestation (range 23-33 weeks). The average age of the patients was
      28 +/- 6 years (range 20-41 years). Six patients were in NYHA Class III and 4 in
      Class IV despite medical treatment. Five patients had mild mitral regurgitation.
      Foetal protection was ensured by covering the mother's abdomen with a lead apron.
      The double balloon technique was used in 4 cases and Inoue's balloon in 6
      patients. The average duration of fluoroscopy was 17 +/- 10 minutes (range 6-37
      minutes). After PMC, the mean pulmonary artery pressure decreased from 47 +/- 12
      mmHg to 31 +/- 11 mmHg (p = 0.005); two dimensional echocardiography showed an
      increase in mitral valve surface area from 1 +/- 0.2 cm2 to 2 +/- 0.3 cm2 (p =
      0.005). There were no complications related to the procedure. The foetal heart
      rate was monitored continuously and no significant modification suggestive of
      foetal distress was recorded. The abdominal cutaneous dose of irradiation was
      less than 0.2 millisievert, which was minimal. All patients experienced a
      functional improvement after PMC. Nine delivered after an average gestation of 38
      +/- 2 weeks (range 36-42 weeks) without cardiac decompensation. The average birth
      weight of the babies was 3.1 +/- 0.3 kg (range 2.9-3.7 kg).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8291948
TI  - Physical medicine and rehabilitation in the 21st century.
AB  - In conclusion, physical medicine and rehabilitation in the 21st century will be:
      new, exciting technologies, different patient populations, different practice
      settings, fewer PM&R residents, and more physician assistants, all operating
      under a universal access, single payer, Canadian-style health care system. I
      began my presentation with a quote from Yogi Berra. I'll close by paraphrasing
      the immortal words of Charles Dickens in the opening lines of A Tale Of Two
      Cities. PM&R in the 21st century will be "the best of times, the worst of times,
      the epoch of belief, the epoch of incredulity."

PMID- 8291949
TI  - Early onset posttraumatic cystic myelopathy complicating spinal cord injury.
AB  - Three cases of posttraumatic cystic myelopathy occurring early in the postinjury
      period are reported. A patient with C5 tetraplegia developed bilateral upper
      extremity paresthesias and right upper extremity weakness 2 and a half months
      postinjury necessitating immediate syringo-subdural shunting. A patient with C6
      tetraplegia complained of left upper extremity paresthesias 2 months postinjury.
      A syringoperitoneal shunt was placed 19 months postinjury due to new onset
      intermittent weakness of the right upper extremity. A patient with C4 tetraplegia
      developed right upper extremity paresthesias, sensory loss, and weakness 56 days
      postinjury; it was treated conservatively. Two years postinjury he required
      surgery because of progression of symptoms. A review of the literature reveals
      that posttraumatic cystic myelopathy has been found to be an incidental
      pathologic finding at autopsy within 2 months postinjury. However, sensory and
      motor loss have not been clinically described as an early complication of spinal
      cord injury. We conclude that posttraumatic cystic myelopathy should be
      considered in the differential diagnosis of motor or sensory loss occurring early
      in the postinjury period.

PMID- 8291950
TI  - Spinal cord injury rehabilitation in a pediatric achondroplastic patient: case
      report.
AB  - Achondroplasia is an autosomal dominant condition that occurs in approximately 1
      of 25,000 births. It has long been associated with neurologic morbidity and
      mortality in adults, but more recently it has been increasingly identified in
      children. Neurological sequelae of achondroplasia includes spinal stenosis,
      spinal cord compression at the foramen magnum (which can result in fatal acute
      craniocervical junction compression), hydrocephalus, radiculopathy, paresis, and
      abnormal spinal curvature. We report the case of a 12-year-old achondroplastic
      patient who incurred an apparently nontraumatic cervical spinal cord infarction,
      with resultant quadriplegia, with no apparent cause, which was complicated by
      impaired tolerance of temperature changes and hypercalcemia of immobilization.
      Whereas persons with achondroplasia have many of the same physical and functional
      impairments from spinal cord injury as other SCI patients, they are more likely
      to experience certain types of neurologic deficits and are more subject to other
      problems because of their altered body habitus.

PMID- 8291951
TI  - Baclofen toxicity in a patient with subclinical renal insufficiency.
AB  - Baclofen, a centrally acting gamma-aminobutyric acid agonist is a commonly used
      pharmacotherapy for spasticity of spinal origin. It is primarily excreted by
      glomerular filtration with a clearance proportional to creatinine clearance. We
      describe a 39-year-old quadriplegic women who, over a 16-week period, developed
      clinical signs of baclofen toxicity confirmed by progressively rising serum
      baclofen levels while on a conventional stable dosing regimen. During this period
      blood urea nitrogen and creatinine concentrations were normal and stable (9mg/dL
      and 0.8mg/dL, respectively). However, creatinine clearance values were
      consistently low (55 to 60m/min), suggesting renal insufficiency as the
      underlying cause. After a decrease in baclofen dosage, evidence of baclofen
      toxicity resolved. Clinicians should be alert to signs of evolving baclofen
      toxicity even in patients on an apparently stable regimen. Baclofen dosage
      adjustments based on systemic baclofen level may play a role in optimizing the
      clinical management of spasticity.

PMID- 8291952
TI  - Osteopenia in patients with above knee amputation.
AB  - Using dual energy x-ray absorptiometry, we studied 16 male patients with
      unilateral above knee amputations (AKA) with a mean age of 48 years (range, 23 to
      66 years) who were full-time prosthetic users for more than 5 years. All
      prostheses were ischial weight bearing. All 16 subjects were found to have normal
      bone density in their spines and in the normal femurs when compared to
      nonamputation controls. However, a significant decrease of mean femoral neck bone
      density was found on the amputated side (0.68g/cm2, range, 0.52 to 1.01) when
      compared to the normal side (1.01g/cm2, range, 0.75 to 1.20) (p < .05). The mean
      bone density percentage difference between the two sides was 28% (range, 4% to
      48%). There was a significantly negative correlation between the patient's age at
      the time of amputation and the severity of osteopenia (-0.73; p < 0.05).

PMID- 8291953
TI  - Enteral tube feeding in a patient with traumatic brain injury.
AB  - Tube feeding is frequently needed for patients with severe traumatic brain
      injury. When the patient is on the rehabilitation unit, bolus type feeding by
      gastrostomy tube is more easily accomplished than continuous type feeding by
      jejunostomy tube (J-tube). In the case presented here, the patient received less
      calories via J-tube feeds while he was on the rehabilitation unit than when he
      was in the intensive care unit or the neurosurgical unit. This has implications
      for the trauma team, which initially decides the type of nutritional support.

PMID- 8291954
TI  - Rachitic syndrome after disodium etidronate therapy in an adolescent.
AB  - A 12-year-old patient with a severe traumatic brain injury developed heterotopic
      ossification (HO) with rapidly decreasing range of motion in multiple joints
      despite intensive passive range of motion exercises and the use of nonsteroidal
      antiinflammatory drugs (NSAIDs). His alkaline phosphatase was markedly elevated.
      Etidronate, 20mg/kg/d was used to control the ossification. After 7 months of
      continual etidronate use, the patient developed periarticular pain with widened
      growth plates, suggesting a rachitic syndrome. Serum laboratory panel including
      calcium, phosphorous, alkaline phosphatase, and vitamin D were normal. After 3
      months off etidronate, radiological studies showed growth plate calcification,
      though not before development of bilateral slipped femoral capital epiphyses.
      Further improvement and resolution of all complications occurred 5 months after
      discontinuation of etidronate. Rachitic syndromes secondary to didronel use in a
      clinical setting has not been previously reported. Other possible causes for a
      rachitic syndromes were not present. Alternate treatments for children with or at
      risk for HO should be considered.

PMID- 8291955
TI  - Persistence of local twitch response with loss of conduction to and from the
      spinal cord.
AB  - A local twitch response (LTR) is a brisk contraction of a taut band of skeletal
      muscle fibers elicited by snapping palpation of a trigger point (TrP) in that
      band. The LTR is a clinically valuable objective sign that confirms the presence
      of a myofascial TrP. A transient burst of electromyographic (EMG) activity can be
      recorded from taut band fibers when an LTR is elicited by snapping palpation of
      TrP. A previous study of the human extensor digitorum muscle during ischemia
      suggested that both central and local pathways can be involved in the propagation
      of LTRs. In this study, EMG activity of LTRs in the third finger extensor muscle
      were recorded bilaterally in a patient with a unilateral brachial plexus lesion.
      This patient had complete loss of nerve conduction involving the posterior cord
      of the right brachial plexus as confirmed by EMG and nerve conduction studies and
      by neurological examination at 6 months after injury. EMG activity (measured as
      discharge duration and maximal amplitude) on the paralyzed side was significantly
      reduced (p < 0.01) as compared with the unaffected side, but had not disappeared.
      Three more studies were done at 7, 8, and 17 months after injury when the motor
      and sensory functions were recovered progressively. The EMG activity of LTRs
      recovered on the paralyzed side in parallel with the motor and sensory recovery.
      These findings indicate that the transmission of LTR depends mainly on the
      central nervous system with a possible minor degree of local transmission.

PMID- 8291956
TI  - Epidural recording of nerve conduction studies and surgical findings in
      radiculopathy.
AB  - We developed a method of studying nerve conduction along proximal nerves and
      nerve roots by delivering supramaximal stimuli to the tibial and peroneal nerves
      within the popliteal space and recording compound nerve action potentials from an
      epidural needle electrode at the L4-L5 interspace. For the purpose of
      investigating lumbar radiculopathies, a battery of averaged potentials was
      developed that could be read side-to-side for symmetry of amplitude and latency.
      Decreased amplitude and/or increased latency in peroneal or tibial conduction
      studies was attributed to L5 or S1 root pathology respectively. We report on 22
      patients who were studied with this method and subsequently went to surgery. To
      evaluate the ability of the procedure to predict surgical findings, we reviewed
      the last 155 patients that we studied using epidural recording to find those who
      had subsequently gone to surgery and were sufficiently documented to allow
      analysis. The review yielded 22 cases and 69 root levels whose condition had been
      reported at surgery and studied by our method. Agreement was above what might be
      expected by chance p < .0001 (7.462; sign). The agreement on nerve root condition
      between nerve conduction studies and surgical findings suggests that the
      procedure's usefulness for confirming and localizing pathology in nerve root
      entrapments is similar to that offered by nerve conduction studies for entrapment
      neuropathies elsewhere.

PMID- 8291957
TI  - Vibrometry testing for carpal tunnel syndrome: a longitudinal study of daily
      variations.
AB  - The method of limits procedure was used to obtain 84 120Hz vibration thresholds,
      over a 3-month period, on four age-matched women with different levels of carpal
      tunnel syndrome (CTS). Each woman used a keyboard for 4 hours a day during work.
      Testing was conducted in a room with a temperature of 28 degrees C +/- 2 degrees
      C after 20 minutes acclimation. Results indicate vibration thresholds vary
      significantly from day to day and also demonstrate how a single vibrometry
      measure may falsely identify the participant's true CTS condition. Specifically,
      a single measure could account for a negative CTS determinations in affected
      wrists or positive CTS determinations in healthy wrists. Subsequent analysis
      revealed menses related fluid retention and day of the week increase the
      vibration thresholds. Analyzing the levels of fluid retention by day of the week
      indicates a compounding effect of the personal and occupational risk factors.

PMID- 8291958
TI  - Combining electrical muscle stimulation with voluntary contraction for studying
      muscle fatigue.
AB  - Short episodes of electrical stimulation were applied to the right quadriceps
      muscle of healthy subjects at different times during 60 second sustained
      voluntary muscle contractions at different levels ranging from 0% to 100% of
      maximal voluntary contraction force. The amplitude of electrically-induced
      increments of torque (delta T) has been shown to depend upon both the level of
      muscular contraction and time from the beginning of the contraction. We have
      considered that the dependence of delta T upon the time from the beginning of
      contraction reflects muscle fatigue. A group of subjects was asked to simulate
      fatigue and to decrease the level of contraction to 50% of the required level.
      They demonstrated strikingly different dependencies of delta T upon time from the
      beginning of contraction. Two kinds of malingering have been analyzed with the
      help of a simple mathematical representation of the dependence of delta T upon
      actual voluntary contraction force. The described method is promising for
      studying muscular fatigue of central and peripheral origin and for detecting
      malingerers.

PMID- 8291959
TI  - Normal limits of side-to-side H-reflex amplitude variability.
AB  - Our hypothesis was that side-to-side difference in the tibial H-reflex amplitude
      can aid in the diagnosis of unilateral S1 radiculopathy with an otherwise normal
      side-to-side H-reflex latency difference. We studied 47 healthy subjects, (mean
      +/- SD, 35 +/- 10 years) using methods similar to those described by Braddom and
      Johnson. Only those with side-to-side latency difference less than 1.5 msec were
      included (n = 45). Current was increased in 0.5 to 1.0 mA increments until the H
      reflex amplitude maximized and then fell; on each side the response with the
      maximal peak-to-peak amplitude was measured for peak-to-peak amplitude and onset
      latency. The amplitude on the side of the smaller response was expressed as a
      ratio of the contralateral amplitude; this mean value (+/- SD) was 0.74 +/- 0.17.
      We conclude that a side-to-side amplitude ratio smaller than 0.4 (mean - 2 SD) in
      the face of a normal side-to-side latency difference is probably abnormal.

PMID- 8291960
TI  - Rehabilitation outcome in children after treatment of primary brain tumor.
AB  - Functional outcome studies after treatment of primary brain tumors in children
      are lacking. This study of 30 children, ages 3 to 20 years (x 10.8 yrs) was aimed
      at documenting the effects of rehabilitation on functional outcome after
      treatment of primary brain tumors. Functional measurements were documented by a
      modified functional independence measure for children (WeeFIM). The paired t
      test, Wilcoxon test, chi 2 analysis, and Friedman test were used to assess
      significance of data. Statistically significant improvements were documented from
      admission to discharge, and discharge to follow-up in total WeeFIM scores (p =
      0.001 and p = 0.0001) and specifically in the subgroups of self care, mobility,
      and locomotion. Though no significant improvement was noted in sphincter control
      from admission to discharge (p = 0.15), significant gains were seen at follow-up
      (p = 0.006). Borderline improvements at discharge in communication (p = 0.054)
      and social cognition (p = 0.051) became significant at follow-up (p = 0.01 and p
      = 0.004). At admission, 7 patients (23%) were independent in self care, 5 (17%)
      in mobility and 1 (3%) in locomotion compared with 18 (60%), 20 (67%), and 15
      (50%) respectively at discharge. At follow-up there was further improvement with
      95% independent in self care, 100% in mobility and 70% in locomotion. This study
      affirms the beneficial effect of comprehensive rehabilitation on functional
      outcome in children with residual disabilities after treatment of their primary
      brain tumors.

PMID- 8291961
TI  - Feedback of triceps surae EMG in gait of children with cerebral palsy: a
      controlled study.
AB  - Children with spastic hemiplegia secondary to cerebral palsy show disrupted
      patterns of work and power in gait. A computer-assisted feedback system was used
      to deliver EMG feedback from the triceps surae muscle group to walking subjects
      in conjunction with amplitude and timing targets for muscle relaxation and
      activation. Biofeedback of triceps surae muscle activity during gait was compared
      with physical therapy (PT) in a two-period crossover design, with intervening
      biomechanical gait analyses to assess the effects of each type of treatment.
      Kinematic and kinetic gait variables were affected differently by each type of
      treatment. Stride length and velocity were positively affected by the biofeedback
      protocol. Positive work done by the affected ankle increased through PT, but gait
      symmetry was negatively affected, such that the stance phase was prolonged, and
      peak ankle power at push-off was not improved. In contrast, the biofeedback
      treatment improved gait symmetry, and was associated with greater ankle power for
      push-off, as well as increases in total positive work at the hip and ankle. It is
      concluded that the feedback protocol might be an effective adjunct to physical
      therapy in hemiplegic children.

PMID- 8291962
TI  - Prospective measurement of functional changes after selective dorsal rhizotomy.
AB  - Selective dorsal rhizotomy (SDR) followed by intensive postoperative therapy is
      commonly performed to reduce spasticity in carefully selected children with
      cerebral palsy. Reduction in spasticity and improvement in range and quality of
      movements are frequently reported. Functional gains have also been indicated but
      have not often been examined in a systematic manner. Twenty-nine children with
      spastic diplegia or quadriplegia received SDR and postoperative physical and
      occupational therapy. Upper-limb movement, self-care, and functional mobility
      were evaluated prospectively through preoperative, 6-month, and 12-month follow
      up examinations. Significant improvements in the Pediatric Evaluation of
      Disability Inventory scores for functional mobility and self-care domains were
      observed for children with spastic diplegia, but not spastic quadriplegia.
      Children's scores in upper-limb reach and coordination tasks did not consistently
      improve. When attributing improvements in self-care and mobility independence to
      SDR and specialized therapy, continued development, new goals, and positive
      beliefs about progress should also be considered as factors influencing outcome.

PMID- 8291963
TI  - Intrathecal baclofen for treatment of intractable spinal spasticity.
AB  - This study assessed the safety and efficacy of intrathecal baclofen in the
      treatment of intractable spasticity caused by spinal cord injury or multiple
      sclerosis. Twenty-three patients with severe chronic spasticity underwent bolus
      test dosing with 50, 75, or 100 micrograms of intrathecal baclofen administered
      by lumbar puncture. All patients were either refractory to oral baclofen at a
      dose of 120 mg/d or side effects were unacceptable at a lower dose. There was a
      significant decrease in tone and spasticity in all 23 patients. Nineteen patients
      underwent implantation of a programmable pump and intrathecal catheter designed
      to deliver baclofen directly to the spinal cord. Rigidity (tone) was decreased
      from a mean prebolus Ashworth score of 3.8 to a mean postbolus Ashworth score of
      1.5 and spasms from a mean prebolus score of 3.5 to a mean postbolus score of 1.2
      for a minimum of 4 hours. Patients have been observed for a mean of 16 months
      (range 2 to 34 months). Ashworth scores have remained reduced to an acceptable
      level (< or = 2 with periodic adjustment in dosage in all but three patients.
      There has been one pump malfunction and four catheter malfunctions; few serious
      medication and postoperative complications have occurred. There was one death
      caused by underlying disease, one patient voluntarily withdrew, and three
      patients developed tolerance to the extent that optimal control of spasticity
      tone could not be maintained. Although intrathecal baclofen is safe and effective
      in the majority of patients, three patients required > 1,000 micrograms/d with
      increasingly higher doses over time and exhibited a poor response.

PMID- 8291964
TI  - Vascular effects of a modified cold pressor test in spinal cord injured and able
      bodied men.
AB  - The vascular reflex responses of the hands of ten spinal cord injured (SCI) men
      (sensory and motor complete) to a modified cold pressor test were compared to ten
      age-matched, able-bodied men. The skin temperature of the left index finger was
      measured before, during, and after the immersion of the feet in ice water for 20
      seconds. The heart rate and blood pressure were measured 5 minutes before and 15
      minutes after the cold stimulus. The able-bodied subjects showed an immediate
      vasoconstriction and fall in finger temperature after cold stimulation of the
      feet, followed by vasodilation and an increase in finger temperature (p < .0001),
      whereas, the SCI subjects did not show any change in finger temperature during
      this test. Prior to application of the cold stimulus, the SCI subjects had a
      significantly low diastolic blood pressure compared with the diastolic blood
      pressure of able-bodied subjects, which "normalized" after the cold stimulus.
      These data support the concept that regulation of vascular tone occurs at both
      spinal and supraspinal levels.

PMID- 8291965
TI  - Phagocytosis of urinary pathogens in persons with spinal cord injury.
AB  - Urinary tract infections (UTI) are a major source of morbidity in persons with
      spinal cord injury (SCI), often prolonging hospitalization, interfering with
      rehabilitation, and leading to secondary urologic complications. Greater
      understanding of host and bacterial factors that may predispose to invasive UTI
      and identification of persons at greatest risk for renal deterioration could
      facilitate development of measures to improve the quality of life for these
      individuals. A prospective investigation of host phagocyte-bacterial interactions
      was undertaken as a means to assess whether persons with SCI who develop renal
      deterioration may be deficient in this important means by which invasive bacteria
      are eliminated from tissues. Neutrophil phagocytic and serum opsonic activities
      against uropathogenic Escherichia coli and Enterococcus fecalis were studied in
      17 persons with SCI who had diminished renal function and 25 persons with SCI who
      had normal renal function. Phagocytic and opsonic activities of neurologically
      intact persons were also comparatively studied as an additional control group. No
      differences in efficiency of opsonization or phagocytosis were detected when
      persons with SCI and impaired renal function were compared with persons with SCI
      who had normal renal function or neurologically intact controls. Whether
      biochemical characteristics of urine or other undefined local aspects of the
      urinary tract influence host-bacterial relationships and urologic outcome
      following SCI are topics worthy of future investigation.

PMID- 8291966
TI  - Motor and sensory recovery following incomplete paraplegia.
AB  - Fifty-four individuals admitted for rehabilitation with a diagnosis of incomplete
      paraplegia due to trauma underwent serial prospective examinations to quantify
      motor and sensory recovery. Motor and sensory scoring guidelines recommended by
      the American Spinal Injury Association were used to assess changes. Lower
      extremity motor scores (LEMS) differed significantly (p < .03) between groups of
      patients partitioned by category of initial neurologic level of injury (NLI) with
      the following averages at 1 month after injury: 6.8 +/- 11.3 above T12, 15.0 +/-
      8.2 at T12 and 18.3 +/- 11.4 below T12. However, the amount of motor recovery was
      independent of the NLI with the differences between the NLI groups remaining
      essentially constant from 1 month to 2 years. While the LEMS increased
      significantly (p < .001) an average of 11.9 +/- 8.7 points between 1 month and 1
      year, the annualized rate of motor recovery rapidly declined in the first 6
      months and then subsequently plateaued. All patients having a 1-month LEMS
      greater than 10 points (28 cases) with hip flexion or knee extension strength >
      or = 2/5 were able to ambulate in the community with a reciprocal gait pattern
      using crutches and orthoses at 1-year follow-up.

PMID- 8291967
TI  - The effects of functional electrical stimulation on shoulder subluxation, arm
      function recovery, and shoulder pain in hemiplegic stroke patients.
AB  - The purpose of this study was to evaluate the effectiveness of a functional
      electrical stimulation (FES) treatment program designed to prevent glenohumeral
      joint stretching and subsequent subluxation and shoulder pain in stroke patients.
      Twenty-six recent hemiplegic stroke patients with shoulder muscle flaccidity were
      randomly assigned to either a control group (n = 13; 5 female, and 8 male) or
      experimental group (n = 13; 6 female, and 7 male). Both groups received
      conventional physical therapy. The experimental group received additional FES
      therapy where two flaccid/paralyzed shoulder muscles (supraspinatus and posterior
      deltoid) were induced to contract repetitively up to 6 hours a day for 6 weeks.
      Duration of both the FES session and muscle contraction/relaxation ratio were
      progressively increased as performance improved. The experimental group showed
      significant improvements in arm function, electromyographic activity of the
      posterior deltoid, range of motion, and reduction in subluxation (as indicated by
      x-ray) compared with the control group. We concluded that the FES program was
      effective in reducing the severity of shoulder subluxation and pain, and possibly
      facilitating recovery of arm function.

PMID- 8291968
TI  - Provocative exercise maneuver: its effect on nerve conduction studies in patients
      with carpal tunnel syndrome.
AB  - This study examined the influence of a provocative dynamic exercise maneuver on
      nerve conduction studies (NCS) in three study groups: Group A, controls (n = 10);
      Group B, patients with clinical carpal tunnel syndrome (CTS), but normal NCS (n =
      10); and Group C, patients with clinical CTS and abnormal NCS (n = 10). A wrist
      flexion-extension exercise was designed to increase pressure on the median nerve
      within the carpal tunnel to aid diagnosis by revealing latent nerve conduction
      slowing in patients presenting with clinical CTS but normal NCS. The exercise
      protocol was sufficient to evoke symptom exacerbation in 50% of the patients. The
      results showed that 4 minutes of this active provocative maneuver revealed a
      significant (p < .05) difference in the sensory distal latency (median) for digit
      IV; however, this was not clinically significant inasmuch as the change in
      latency was insufficient to meet the a priori criteria for NCS abnormality
      required for the electrodiagnosis of median nerve abnormality. There was no
      increase in the distal sensory latencies of those patients whose symptoms were
      exacerbated, when compared with those patients whose symptoms remained unchanged.
      There appears little diagnostic value in adding this particular active
      provocative wrist maneuver to the routine electrodiagnostic evaluation for carpal
      tunnel syndrome.

PMID- 8291969
TI  - Serum albumin level as a predictor of geriatric stroke rehabilitation outcome.
AB  - This study examined the value of serum albumin level as a predictor of medical
      complications and functional outcomes in 79 patients, age 65 years or older, who
      underwent comprehensive inpatient interdisciplinary rehabilitation for a first
      time, unilateral, thromboembolic stroke. We recorded serum albumin levels at the
      time of admission to an inpatient rehabilitation unit, reports of the medical
      complications during rehabilitation, and Modified Barthel Index (MBI) Scores on
      admission and discharge. The mean (+/- SD) serum albumin level for all patients
      was 3.3 +/- 0.4g/dL. Forty-two patients (53%) had a total of 69 medical
      complications during rehabilitation. Mean serum albumin levels were 3.2 +/-
      0.4g/dL for the group with complications and 3.5 +/- 0.3g/dL for the group
      without complications (t = -4.34, p < 0.001). Of the 37 patients with albumin
      levels > or = 3.5g/dL, only 32% had complications; of the 28 patients with levels
      from 3.0 to 3.4g/dL, 68% had complications; of the 14 patients with levels < or =
      2.9g/dL, 79% experienced complications (chi 2 = 12.4, p = 0.002). There were
      positive correlations between serum albumin levels and the discharge MBI Self
      Care Subscores, Mobility Subscores, and Total Scores (p < 0.001). There were also
      correlations between serum albumin levels and the Mobility and Total MBI
      Improvement Scores (p = 0.002 and p = 0.008, respectively). The relationship
      between serum albumin levels discharge destination approached statistical
      significance. Neither age nor side of lesion were related to serum albumin level,
      medical complication rate, or functional outcomes. Serum albumin levels appear to
      be related to medical complication rate and functional outcome in geriatric
      stroke patients. This suggests that older stroke patients with hypoalbuminemia
      may warrant closer medical attention or therapeutic intervention before and
      during rehabilitation.

PMID- 8291970
TI  - Biomechanics of wheelchair propulsion during fatigue.
AB  - Musculoskeletal injuries can result from overuse or incorrect use of manual
      wheelchairs, and can hinder rehabilitation efforts. The purpose of this study was
      to investigate wheelchair propulsion biomechanics of spinal cord injured, non
      athletic wheelchair users. We studied changes in the variables that occur with
      fatiguing wheelchair propulsion to determine how the user's physical
      characteristics and the state of fatigue influence risk of injury. Twenty male
      paraplegic patients were videotaped during propulsion to fatigue on a stationary,
      instrumented wheelchair positioned on a roller with adjustable frictional
      resistance. Peak handrim force was significantly correlated with concentric
      shoulder flexion and elbow extension isokinetic torques. Significant changes (p <
      0.05) with fatigue were found in increased peak handrim force, decreased
      ulnar/radial deviation range of motion, and increased trunk forward lean. Of the
      three upper extremity joints, highest calculated joint moments were found in
      shoulder flexion (p < 0.05). These biomechanical results suggest that potentially
      harmful changes occur with fatigue, and that the shoulder may be the most prone
      to musculotendinous-type overuse injury.

PMID- 8291971
TI  - Heart disease in patients with stroke. Part II: Impact and implications for
      rehabilitation.
AB  - Cardiac disease reduces the long-term survival of stroke patients and increases
      the likelihood of intercurrent medical illness during the rehabilitation phase.
      It remains controversial whether heart disease negatively affects functional
      capabilities after stroke, but most studies agree that associated cardiac
      disease, especially congestive heart failure, adversely affects functional
      outcomes after stroke rehabilitation. Reliable clinical assessment of the
      presence and severity of heart disease in stroke patients may be hampered by
      mobility limitations, communication deficits, and other problems. Therefore,
      specialized diagnostic methods may be needed. The development and application of
      effective and consistent medical and rehabilitation guidelines for proper
      comprehensive care may enhance the likelihood of achieving favorable outcomes and
      of avoiding complications in patients with stroke.

PMID- 8291972
TI  - Sacrococcygeal teratoma in children: a diagnostic challenge.
AB  - Sacrococcygeal teratoma is relatively rare. Its characteristic appearance,
      location and size usually leave little doubt as to the diagnosis, but the less
      obvious ones may occasionally give rise to diagnostic difficulty. Four cases of
      sacrococcygeal teratoma in children are reported. One neonate presented with a
      large protuberant swelling at the sacrococcygeal area, with no diagnostic
      difficulty. The second neonate presented with a small paraxial sacral swelling
      with an overlying haemangioma. The third patient presented with a small tail-like
      appendage at the natal cleft. A properly performed rectal examination in both the
      second and third patients disclosed the diagnosis. The fourth patient presented
      with an anocutaneous fistula and partial sacral agenesis with no external
      sacrococcygeal swelling. The diagnosis was confirmed with computerized
      tomography. While the diagnosis of the protuberant sacrococcygeal teratoma
      presents no difficulty, that of the less obvious cases requires a high index of
      clinical suspicion. A properly performed rectal examination supplemented with
      appropriate imaging allows the diagnosis to be made.

PMID- 8291973
TI  - Early and late results after Bird's Nest filter placement in the inferior vena
      cava: clinical and duplex ultrasound follow up.
AB  - From February 1989 to November 1992, 61 Bird's Nest filters were placed in the
      infrarenal vena cava in 61 patients (36 men and 25 women; mean age +/- s.d., 63
      +/- 15, range (16-83). In 27 (44.3%), the filter was inserted because of
      contraindication to anticoagulation, in 19 (31.1%) for anticoagulation failure
      and in 15 (24.6%) as prophylaxis against pulmonary embolism in high risk
      patients. All the filters were introduced by percutaneous puncture of the femoral
      vein after preliminary screening venography demonstrated that the iliac vein was
      free of thrombus. Two deaths occurred within 24 h of filter placement
      (periprocedure mortality 3.3%) while five other patients died within 1 month (30
      day cumulative mortality 11.5%). At follow-up, 2-40 months later (mean +/- s.d.,
      17 +/- 9), a further 13 patients had died (cumulative mortality 32.8%). At 36
      months, the probability of survival, calculated by the Kaplan-Meier Product Limit
      Method, was 55% (95% confidence intervals 37-74%). Apart from the two patients
      dying within 24 h, none of the early or late deaths were attributable to the
      procedure and there were no recurrent pulmonary emboli. Thirty-seven of the
      surviving 41 patients were recalled for clinical examination and Duplex
      ultrasound interrogation of the vena cava and the lower limb veins. No new venous
      thromboses in the legs were observed and no increase or onset of leg swelling was
      reported. The vena cava patency was 100% in these 37 patients.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8291974
TI  - The psychological impact of hip arthroplasty.
AB  - The impact of total hip arthroplasty on psychological functioning was examined in
      51 patients; 25 females and 26 males with a mean age of 65 years (range 42-81
      years). Assessments of psychological well-being and distress were made with the
      Mental Health Inventory. Life satisfaction, self-rated health, and pain ratings
      were also obtained. Assessments were made prior to surgery, immediately after
      surgery, and at a 2 month follow-up. The operation produced significant
      improvements in psychological well-being (P < 0.001), psychological distress (P <
      0.001), life satisfaction (P < 0.01), self-rated health (P < 0.001), and pain (P
      < 0.001). It is concluded that the changes in medical and functional status
      following hip arthroplasty documented in previous research are accompanied by
      substantial improvements in psychological state, and that the inclusion of
      psychological factors in hip arthroplasty research will provide a more
      comprehensive assessment of outcome.

PMID- 8291975
TI  - Around the rim: the role of surgeons in discovery and research in the Pacific
      rim. Part II. Surgeons in the Pacific: colonists and scientists.

PMID- 8291976
TI  - Problems with the design of observations and their statistical analysis.

PMID- 8291977
TI  - Fatal haemoperitoneum due to rupture of hepatic metastasis from renal cell
      carcinoma.

PMID- 8291978
TI  - Emphysematous cholecystitis can cause pneumoperitoneum.
AB  - A case of emphysematous cholecystitis with gall-bladder perforation, resulting in
      free intraperitoneal gas, is presented. It adds to only nine previous reports. A
      successful outcome was achieved by early surgery, combined with appropriate
      antibiotic therapy.

PMID- 8291979
TI  - Plastic bowing of the forearm in the more mature skeleton.
AB  - An 18 year old male suffered plastic bowing of both forearm bones following an
      industrial accident in which his forearm was caught by an electric hoist. Plastic
      bowing of both the radius and ulna occurred. This deformity, usually seen in
      children, was produced by an unusual set of circumstances, with a transverse
      force being applied for a considerable time. All four cases of 'adult' plastic
      bowing deformity have been the result of industrial accidents and were always the
      result of a transverse force acting upon the limb. Although, initially, after
      manipulation there was only minimal improvement in range of movement, progressive
      improvement was achieved with physiotherapy. In the present case early
      mobilization resulted in a good functional outcome for the patient.

PMID- 8291980
TI  - Lingual thyroid.
AB  - Lingual thyroid is a rare cause of dysphagia and airway obstruction. A case is
      presented, with a discussion of the diagnosis and management.

PMID- 8291981
TI  - Complication of hard cervical collars in multi-trauma patients.
AB  - All multi-trauma patients with suspected cervical spine injury should have their
      cervical spine protected while other life-threatening injuries are being managed.
      The application of a hard cervical collar is an acceptable method of temporarily
      immobilizing the cervical spine. Two cases of significant occipital pressure
      ulceration associated with the use of hard cervical collar are presented.

PMID- 8291982
TI  - Changes in the practice of biliary surgery and ERCP during the introduction of
      laparoscopic cholecystectomy to Australia: their possible significance.
AB  - Two and a half years after the introduction of laparoscopic cholecystectomy to
      Australia in February 1990, estimates from Medicare statistics suggest that by
      July 1992, 69% of cholecystectomies were being performed laparoscopically. There
      was a smaller decline in the numbers of open cholecystectomies performed,
      suggesting a 28% rise in the rate of cholecystectomy. This has been associated
      with a 66% decline in the use of intra-operative cholangiography. Whereas 87% of
      cholecystectomies had an operative cholangiogram performed, now only 23% of all
      cholecystectomies do. It is suggested that in approximately half the patients, no
      attempt is made to exclude common duct stones. With those patients in whom an
      attempt is made, most surgeons rely on endoscopic retrograde
      cholangiopancreatography, as evidenced by a 43% increase in its use, or, more
      recently, a small proportion of surgeons have been using intravenous
      cholangiography, as evidenced by a 26% increase in its use. Once diagnosed, these
      stones are no longer being treated by open exploration of the bile duct,
      indicated by a 46% decrease in this procedure, but are being treated by
      endoscopic sphincterotomy, which has shown a 242% increase in its use. From the
      published results of the outcome of these treatments, the added risk, nationally,
      of these additional procedures in managing uncomplicated bile duct stones is
      predicted to increase mortality 1-3-fold and morbidity 10-15-fold. This risk can
      be reduced by the use of laparoscopic bile duct exploration. These techniques are
      already well established and can be learnt quickly if practice is achieved by
      performing routine intra-operative cholangiography.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8291983
TI  - Early experience with minimally invasive surgery: a New Zealand audit.
AB  - The clinical and economic impact of minimally invasive surgery in New Zealand,
      especially laparoscopic cholecystectomy, has been profound but uncharted. A
      postal questionnaire was sent to all general surgeons in New Zealand (n = 214),
      in order to document the current levels of experience, adequacy of training,
      levels of equipment and sources of funding. In the case of laparoscopic
      cholecystectomy, further details were obtained relating to operative technique,
      complication rates and approaches to the management of choledocholithiasis. The
      response rate was 71%. From 27 centres, 71 of 106 active general surgeons were
      performing minimally invasive surgery. Of the 34 different procedures audited,
      cholecystectomy (3056), herniorrhaphy (178), and appendicectomy (141) were
      performed most often. Primary funding came from Area Health Boards (71%) and
      private hospital funds (25%) with 4% coming from other sources. Ten different
      camera/insufflator systems were used. Training was perceived to be adequate by
      the majority of surgeons (89%), although seven surgeons had received no specific
      training. Laparoscopic cholecystectomy technique included: prophylactic
      antibiotics (89% of surgeons), patients supine (80%), wound infiltration (80%),
      routine use of diathermy within triangle of Calot (36%) and a routine peritoneal
      drain (13%). Routine operative cholangiography was used rarely (7%) and 72% of
      surgeons had deliberately changed their policy with respect to its use. Twenty
      two cases of laparoscopic biliary injury were identified by the survey, none of
      whom had operative cholangiography. The conversion rate was 13% for acute and 4%
      for elective laparoscopic cholecystectomy. This survey indicated the broad scope
      of minimally invasive surgery that is being undertaken, and highlights
      potentially important variations in surgical practice.

PMID- 8291984
TI  - Clam cystoplasty for the overactive bladder: a review of 23 cases.
AB  - A clam enterocystoplasty was performed for refractory urge incontinence due to
      either idiopathic instability (13 patients) or neuropathic hyperreflexia (10
      patients). Twelve patients became dry and appliance free. Of the remaining 11 wet
      patients, seven developed low pressure reservoirs, of whom five had stress
      incontinence and two had overflow incontinence. The other four patients had
      persistent symptomatic involuntary phasic contractions and ongoing urge
      incontinence. The magnitude of the surgery and the voiding dysfunction associated
      with the relative lack of motivation of elderly patients made the operation less
      successful and more hazardous in those over the age of 65. Successful outcome
      could be improved by careful patient selection and by performing an antistress
      incontinence procedure, such as implantation of an artificial urinary sphincter
      cuff or a cystourethropexy, where there is associated bladder outlet
      incompetence.

PMID- 8291985
TI  - Costing transurethral resection of the prostate and diagnosis related group in
      Australia compared with United States costs.
AB  - The cost of a transurethral resection of the prostate is of considerable concern
      to the community. More of these procedures are being performed as the number of
      patients in the aged population increases. The costs of wages and salaries,
      purchase of equipment and depreciation, stationery, linen, investigations
      (pathology) and pharmaceuticals are compared with the bed charges (as charged to
      a private patient), the cost per inpatient day and the cost per inpatient
      treated, which is calculated from the operating fund budget expenditure of The
      Bendigo Hospital. The cost per diagnosis related group (DRG) 336 (defined as:
      transurethral prostatectomy, age greater than 69 and/or complication/co
      morbidity; mean length of stay 7.0; relative weight = 0.9869) and DRG 337
      (defined as: transurethral prostatectomy, age less than 70 without
      complication/co-morbidity; mean length of stay 5.8; relative weight = 0.7788) are
      compared with the figures for a similar procedure in 1987 in a United States
      hospital and extrapolated, by the use of the Consumer Price Index, to 1992
      levels. The findings demonstrate that transurethral resection of the prostate as
      costed in this hospital compares very favourably with that in a US hospital, and
      favourably from the point of view of health care costs.

PMID- 8291986
TI  - Urolithiasis in Australian aboriginal children.
AB  - Thirty-six Australian Aboriginal children with urolithiasis were reviewed. Males
      dominated the series. The age distribution ranged from 8 months to 12 years and
      nearly 70% were 2 years or younger. Thirty-five patients had upper tract stones.
      Ultrasound was diagnostic in 35 patients and was falsely negative in one. Dietary
      factors, dehydration and recurrent diarrhoea are incriminated in the aetiology,
      because ammonium urate and oxalate were the main constituents of the stones.
      Malformations of the urinary tract were rare and known metabolic disorders were
      not seen. Chemical dissolution of the stones was found to be a safe and effective
      adjuvant in the management of urate stones.

PMID- 8291987
TI  - Relating alcohol-induced performance deficits to mental capacity: a suggested
      methodology.
AB  - Performance tests are generally more reliable and more easily administered than
      on-the-job measures of performance, and in this way are preferable for studying
      the adverse consequences of environmental stressors. However, a linkage or
      context would be useful in interpretation of these laboratory measures. This
      paper reports findings with two indexing methods using multiple regression. In
      the first study, we illustrate "dose equivalency" where deficits on microcomputer
      performance tests were related to graded dosages of alcohol, and prediction
      equations of blood alcohol level were established. In the second experiment,
      "surrogate criteria" are demonstrated where cognitive mental tests of military
      aptitude, known to be predictive of operational performances, were administered
      to a sample who were tested repeatedly on the same microcomputer performance
      test. Multiple regression analyses of the computerized tests with the amplitude
      tests were significant (p < 0.01) and ranged from R = 0.50 to 0.94. Finally, the
      loss in performance owing to alcohol was indexed to loss on the microcomputer
      tests through the relationship of the tests to the Armed Services Vocational
      Aptitude Battery (ASVAB). Since the latter is strongly predictive of all forms of
      military operational performance, we suggest that alcohol-related losses in
      microcomputer performance test scores can serve as a useful intermediary,
      permitting meaningful linkage to these real-world performances.

PMID- 8291988
TI  - Work performance at 40 degrees C with Canadian Forces biological and chemical
      protective clothing.
AB  - This study examined the effects of a hot environmental temperature (40 degrees C
      and 50% relative humidity) and metabolic rate on soldiers' tolerance time (TT)
      while wearing various levels of the Canadian Forces biological and chemical (BC)
      defence protective clothing. The subjects, 19 unacclimatized males, were assigned
      to exercise at either a light intermittent (LI) (N = 4), light continuous (LC) (N
      = 5), moderate continuous (MC) (N = 5) or heavy continuous (HC) (N = 5) metabolic
      rate. For groups LI and LC, exercise involved walking on a treadmill at 4.0 km.h
      1 with a 0% grade and lifting 10 kg boxes. LI alternated between 15 min of
      exercise and 15 min of rest. Group MC walked at 4.8 km.h-1 with a 3% grade and
      lifted 15 kg boxes. Group HC walked at 4.8 km.h-1 with a 7.5% grade and lifted 20
      kg. Subjects were tested wearing three levels of clothing protection: combat
      clothing (L); combat clothing and a semi-permeable BC overgarment (M); combat
      clothing and BC overgarment, gloves, boots and respirator (H). TT was the time
      until rectal temperature reached 39.3 degrees C, heart rate reached 95% maximum,
      dizziness or nausea precluded further exercise, or 5 h had elapsed. For group LI,
      TT was similar for L (137 +/- 15 min) and M (117 +/- 9 min) clothing. TT was
      significantly reduced for H (67 +/- 6 min) clothing. For group LC, TT was greater
      for L (91 +/- 11 min) compared with either M (68 +/- 7 min) or H (55 +/- 2 min)
      clothing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8291989
TI  - Effect of extending G-suit coverage on cardiovascular responses to positive
      pressure breathing.
AB  - The purpose of this study was to compare cardiovascular responses of subjects
      exposed to long-duration positive pressure breathing (PPB) while wearing a
      standard (Combat Edge; CE) vs. extended coverage (Tactical Life Support System;
      TLSS) G-suit. Twelve experienced subjects, wearing TLSS and CE, were separately
      exposed to counterbalanced 60, 70, 80, and 88 mm Hg PPB for up to 10 min
      continuously. Termination resulted if presyncopal symptoms arose. G-suit
      inflation was 4 x mask/jerkin pressure. Using TLSS, all subjects completed 10 min
      of PPB at all levels, vs. 7 and 5 subjects completing 10 min at 80 and 88 mm Hg,
      respectively, using the CE ensemble (p < 0.001). Heart rate was significantly
      elevated at all PPB levels using CE (p < 0.0001) vs. TLSS. Stroke and Cardiac
      Indexes were significantly lower with CE at all levels vs. TLSS (p < 0.0001), and
      mean arterial blood pressure failed to be maintained at the 80 and 88 PPB mm Hg
      levels using CE (p < 0.0001). Extended G-suits afford superior protection against
      PPB-induced cardiovascular dysfunction vs. standard ensembles and consequently
      permit use of higher levels of PPB. This is due to the larger and more uniform
      application of pressure in the leg G-suit bladders, augmenting venous return and
      stroke volume.

PMID- 8291990
TI  - Suppression of shivering by breath holding, relaxation, mental arithmetic, and
      warm water ingestion.
AB  - Four methods of suppressing cold-induced shivering were evaluated in 26 young
      male volunteers exposed to 0.0 +/- 1.0 degrees C air for 135 min. Voluntary
      relaxation of musculature (R), breath holding (BH), warm (50 degrees C) water
      ingestion (W), and performance of a mental arithmetic task (MA) were applied in a
      counterbalanced order following 2 h of cold exposure. Surface electromyograms of
      seven muscles were recorded and converted to root mean square voltage (RMS) as a
      measure of shivering intensity. Mean skin and rectal temperatures decreased
      significantly, 4.9 degrees C and 0.3 degrees C, respectively (p < or = 0.01).
      Mean reduction of EMG activity was 35% during R, 24% during BH, 18% during MA,
      and 5% during W. R was significantly more effective than BH, MA, and W, and BH
      and MA were significantly more effective than W in reducing shivering. These
      results indicate that, at small decreases in rectal temperature, shivering can be
      voluntarily suppressed to some extent during relaxation, breath holding, and
      mental arithmetic.

PMID- 8291991
TI  - Responses of Arctic and tropical men to a standard cold test and peripheral
      vascular responses to local cold stress in the Arctic.
AB  - Thermoregulatory, metabolic and peripheral vascular responses to cold were
      studied in two groups (six each) of healthy men during exposure to the natural
      cold environment of the Arctic. Group A comprised of two arctic natives and four
      temporary residents who had migrated from the temperature zone of Russia. Group B
      consisted of six soldiers from a tropical region (India). Group B was airlifted
      to the arctic (70 degrees N, 38 degrees E). Both groups stayed in a field camp.
      The experiments were conducted during the 7th week of the stay. The volunteers
      were subjected to a standard cold test at 10 degrees C for 2 h wearing only
      shorts. Their heart rate, blood pressure, ventilation, oxygen consumption, oral
      temperature, mean skin and extremity temperatures were recorded initially and at
      30 min intervals during standard cold test. The cold-induced vasodilatation
      response in both groups was also studied separately. The tropical natives (Group
      B) were flown back to Delhi and retested after 6 weeks. The physiological
      responses to general cold exposure as well as peripheral vascular response to
      local arctic cold stress were similar in both groups. The observation suggested
      that cold acclimatization in tropical men is similar to that of the people of
      Russian origin from a temperature zone.

PMID- 8291992
TI  - Factors influencing success or failure in the AH-64 course.
AB  - A greater percentage of qualified student pilots fail the AH-64 (Apache)
      transition than any other advanced aircraft transition in the Army. We studied
      140 consecutive students presenting for training in an effort to identify factors
      which might predict success or failure in the AH-64 course. Questionnaires were
      used to elicit demographic, anxiety level, and motion sickness history
      information prior to beginning Apache flight training. Motion sickness symptoms
      (MSS) during the enclosed cockpit, or "bag," phase of training were quantified
      using pre- and postbag flight symptom questionnaires. Performance measures
      included grades and flight hours required to pass the course. Only one piece of
      information obtained prior to flight training was related to performance in the
      AH-64 course; i.e., students who requested the transition performed measurably
      better than students who did not. While 7% of pilots described significant MSS on
      the first day of enclosed cockpit flight, this decreased to 2% by day 5. Severity
      of symptoms during bag phase was not related to any measure of subsequent
      performance.

PMID- 8291994
TI  - Natural killer cell activity during head-up tilt-induced central hypovolemia in
      humans.
AB  - Changes in immunological competent blood cells were evoked in seven humans during
      passive head-up tilt (50 degrees anti-Trendelenburg's position maintained until
      appearance of presyncopal symptoms). Blood samples were collected after 60 min of
      rest, when presyncopal symptoms appeared during tilt, and 105 min after tilt
      down. Natural killer (NK) cell activity increased during head-up tilt due to a
      three to four-fold increase in CD16+ NK cells in blood. In support NK cell
      activity boosted with interferon-alpha and interleukin 2 (IL-2) rose in parallel
      with unboosted NK cell activity. This effect on NK cells disappeared during
      recovery but was not suppressed when compared to prevalues. Lymphocyte
      concentration also increased during head-up tilt. Concentrations of CD3+ and CD4+
      T cells were almost stable during head-up tilt, whereas the percentage of CD3+ T
      cells in relation to blood mononuclear cell (BMNC) concentration decreased, due
      to a diminished percentage of CD4+ T cells and the marked simultaneous increase
      in the percentage of CD16+ NK cells. Although changes in the BMNC composition
      occurred, the proliferative responses of BMNC following stimulation with
      phytohemagglutinin, purified derivative of tuberculin, or IL-2 did not change
      significantly. We conclude that head-up tilt induced marked changes in
      subpopulations of BMNC, especially the CD16+ NK cells, as they were recruited to
      the blood.

PMID- 8291993
TI  - Comparative study of the levels of antioxidants of students at Amman and Dead Sea
      level.
AB  - The effect of hyperoxia on the level of the antioxidants: glutathione (GSH) in
      the whole blood and the enzymes, catalase, superoxide dismutase (SOD), glucose-6
      phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6-PGD), was
      studied in the erythrocytes of male high school students living at Dead Sea level
      (390 m below Sea level and 794.7 mm Hg), and compared with those of students
      living at Amman level (766 m above sea level and 697.5 mm Hg). The levels of the
      antioxidant enzymes were found to be lower at Dead Sea level than in Amman,
      except for the catalase level, which was similar in both groups. The ratio of
      GSH/Hb was significantly higher in the blood of students at Dead Sea level than
      in Amman. The combined activities of the antioxidants protected the RBC's but
      permitted increased level of GSH/Hb in the blood to protect peripheral cells from
      damage by oxidants.

PMID- 8291995
TI  - Use of a disposable carbon dioxide detector with emergency intubation in a
      hyperbaric chamber.
AB  - Emergency intubation in a hyperbaric chamber can be complicated by the confined
      space, inadequate lighting and high levels of background noise. Inadvertent
      esophageal intubation may be difficult to recognize in these conditions. In more
      controlled settings such as the operating room, the detection of end-tidal carbon
      dioxide is the standard procedure for verifying proper placement of the
      endotracheal tube. Within a hyperbaric chamber, a capnograph may not be readily
      available for this purpose. We present a case report describing the use of a
      simple disposable colorimetric carbon dioxide detector for rapid verification of
      endotracheal tube position following emergency intubation in a hyperbaric
      chamber.

PMID- 8291996
TI  - 39th annual Louis H. Bauer Lecture: Cultural differences--facilitators or
      hindrances to global civil aviation medical standards.

PMID- 8291997
TI  - Civil aeromedical standards: year 2000 plus.
AB  - Civil aviation medical standards are continuing to evolve from those established
      in the World War I era. For example, the whispered voice test standards, the
      uncorrected visual acuity standards, and other holdovers have been modified, and
      these and others are now undergoing further modification. U.S. civil pilot ECG's
      are all now being sent by telephone to the FAA, and, beginning in 1992, some
      Aviation Medical Examiners are sending the airman physical examinations to the
      FAA by telephone. By 1994, the vast majority of these examinations are to be sent
      electronically. As cognitive function is the primary factor in safe flight
      operations, computerized assessments of this aspect will be accomplished
      routinely in the next century, taking precedence over physical characteristics
      which in earlier times were given priority.

PMID- 8291998
TI  - Cases from the aerospace medicine residents' teaching file. Case H56. Pilot
      incapacitation of psychiatric etiology (PIPE)
AB  - A case is presented which involves a fighter pilot with anxiety disorder and in
      flight panic attacks. The initial presentation, clinical course, evaluation, and
      aeromedical disposition are all discussed.

PMID- 8291999
TI  - Aircraft transmission of TB.

PMID- 8292000
TI  - Discerning the function of p53 by examining its molecular interactions.
AB  - Of the many genes mutated on the road to tumor formation, few have received as
      much attention as p53. The gene has come to occupy center stage for the simple
      reason that it is more frequently altered in human tumors than any other known
      gene, undergoing mutation at a significant rate in almost every tumor type in
      which it has been studied. This association between p53 mutation and
      tumorigenesis has spurred a flurry of research attempting to delineate the normal
      function of p53 and, by extension, the role of p53 mutation in tumor formation.
      At the cellular level, p53 has been shown to suppress growth. Recent efforts to
      further discern the function of p53 have centered on the underlying molecular
      basis for this growth suppression. In particular, research has focused on the
      identification of cellular molecules (specifically DNA and proteins) with which
      the p53 protein associates. p53 has now been shown to bind DNA in a sequence
      specific manner, and mounting evidence suggests that p53 acts as a transcription
      factor, perhaps regulating the expression levels of genes involved in the
      inhibition of cell growth. The logical next step in understanding p53 function
      involves the resolution of two questions: (1) what are the physiological
      transcriptional targets of p53, and (2) what cellular proteins regulate or
      mediate the ability of p53 to modulate transcription? Some initial clues to these
      puzzles are now emerging, and these form the subject of this review.

PMID- 8292001
TI  - Dynamics of DNA methylation during development.
AB  - DNA methylation plays a role in the repression of gene expression in animal
      cells. In the mouse preimplantation embryo, most genes are unmethylated but a
      wave of de novo methylation prior to gastrulation generates a bimodal pattern
      characterized by unmethylated CpG island-containing housekeeping genes and fully
      modified tissue-specific genes. Demethylation of individual genes then takes
      place during cell type specific differentiation, and this demodification may be a
      required step in the process of transcriptional activation. DNA modification is
      also involved in the maintenance of gene repression on the inactive X chromosome
      in female somatic cells and the marking of parental alleles at genomically
      imprinted gene loci.

PMID- 8292002
TI  - Pure thoughts with impure proteins: permeabilized cell models of organelle
      motility.
AB  - Permeabilized cell models provide an experimental middle ground wherein the in
      vitro properties of mechanochemical proteins can be reconciled with the physical
      and topological constraints of the intact cell. Several well-studied examples of
      organelle motility are described here, including the actin-based cytoplasmic
      streaming of Characean algae, the microtubule-based aggregation and dispersion of
      pigment granules in chromatophores and the saltatory movements of vesicles along
      microtubules in fibroblasts and macrophages. The permeabilized models developed
      for these systems have helped to integrate observations in vivo with in vitro
      assays of motor proteins.

PMID- 8292003
TI  - The ascidian embryo as a prototype of vertebrate neurogenesis.
AB  - Ascidian tadpole larvae, composed of only about 2500 cells, have a primitive
      nervous system which is derived from the neural plate. The stereotyped cell
      cleavage pattern and well characterized cell lineage in these animals allow the
      isolation and culture of identified blastomeres in variable combinations.
      Ascidian embryos express cell-type-specific markers corresponding to their cell
      fates, even when cultured under cleavage-arrest by cytochalasin B. This system
      provides us with a unique opportunity to study the roles of cell lineage and cell
      contact in early neuronal differentiation in the absence of events associated
      with complex morphogenesis. In addition, the isolated, cleavage-arrested
      blastomeres are ideally suited to electrical recording, permitting the use of
      ionic channels as specific markers for differentiation. In the cleavage-arrested
      embryos, suppression of one type of K+ channel, and induction of two types of Na+
      channels, occur following cell contact with the vegetal blastomere. The
      combination of molecular and electrophysiological analyses on this simple animal
      system may provide insights into the nature of the cell interactions important in
      early neurogenesis, both in ascidians and in vertebrates.

PMID- 8292004
TI  - Movement of virus and photoassimilate in the phloem: a comparative analysis.
AB  - Recent progress in the study of short-distance (cell-to-cell) movement of plant
      virus, facilitated by 'movement proteins', has led to a resurgence of interest in
      long-distance virus transport in the phloem. Relatively little is known about
      phloem-specific barriers to virus movement or about the form in which virus
      enters, travels within and exists this tissue. Progress in understanding virus
      and photoassimilate transport is limited by a paucity of information on the
      substructure and properties of plasmodesmata at specific interfaces. The
      direction of virus movement, once it has entered the phloem, can be understood by
      following photoassimilate translocation, a complex and dynamic process influenced
      by plant growth, development and vascular topology.

PMID- 8292005
TI  - Human UDP-glucuronosyl transferases: chemical defence, jaundice and gene therapy.
AB  - Human UDP-glucuronosyltransferases (UDPGTs) are a family of enzymes which
      detoxify many hundreds of compounds by their conjugation to glucuronic acid,
      rendering them both harmless and more water soluble, hence, excretable. The level
      of expression of each UDPGT isoform in the body is the result of interplay
      between temporal, tissue-specific and environmental regulators. This complexity
      contributes to the difficulty in predicting the metabolic fate of compounds.
      Genetic defects and polymorphisms affecting individual isoform activities have
      deleterious and potentially lethal effects, as exemplified by the severe
      hyperbilirubinaemia observed in Crigler-Najjar Syndrome. Such severe genetic
      defects in bilirubin glucuronidation are obvious candidates for antenatal
      screening and gene therapy.

PMID- 8292006
TI  - Glowing reports on biorhythm research.

PMID- 8292007
TI  - In search of the machinery for spatial patterning of animal epithelia.

PMID- 8292008
TI  - Ligation-based DNA diagnostics.
AB  - A number of novel gene detection techniques all revolve around the ligation of
      synthetic nucleic acid probes. In such ligase-assisted gene detection reactions,
      specific DNA or RNA sequences are investigated by using them as guides for the
      covalent joining of pairs of probe molecules. The probes are designed to
      hybridize immediately next to each other on the target nucleic acid strand.
      Demonstration of ligated probes results in highly specific detection of and
      efficient distinction between similar sequence variants under standard reaction
      conditions. Accordingly, the principle has been applied in automated genetic
      screening procedures. Ligation reactions are also integral to a number of
      amplification procedures and they will be of value in an expanding range of
      genetic analyses.

PMID- 8292009
TI  - Regulatory effect of phorbol esters on sphingosine kinase in BALB/C 3T3
      fibroblasts (variant A31): demonstration of cell type-specific response--a
      preliminary note.
AB  - Sphingosine-1-phosphate (Sph-1-P) has been implicated as a second messenger in
      control of cell motility and proliferation (e.g., Sadahira Y, et al., PNAS
      89:9686, 1992; Olivera A & Spiegel S, Nature 365:557, 1993). The control
      mechanism for its synthesis, as catalyzed by sphingosine kinase, is crucial in
      signal transduction. Synthesis of Sph-1-P in Balb/c 3T3 fibroblasts (A31 variant)
      is strongly up-regulated by brief treatment of cells with 12-O
      tetradecanoylphorbol-13-acetate (TPA). Level of Sph-1-P in PKC-depleted cells is
      10-fold higher than in undepleted cells, and a further 5-fold increase occurs
      after treatment with TPA. In Swiss 3T3 and B16 melanoma cells, Sph-1-P level was
      unaffected by TPA treatment. Thus, the effect of TPA on Sph-1-P synthesis appears
      to be cell type-specific.

PMID- 8292010
TI  - Plasmin converts pro-form of group I phospholipase A2 into receptor binding,
      active forms.
AB  - Treatment of zymogen of pancreatic-type group I phospholipase A2 (PLA2-I) by
      plasmin, a fibrinolytic enzyme, increases PLA2 activity as well as receptor
      binding activity in a dose- and time-dependent manner. Separation of plasmin
      treated pro-PLA2-I by HPLC and amino acid sequence analysis of the products
      revealed that, in addition to an authentic mature PLA2-I produced by trypsin,
      plasmin produced active products which had been modified in the C-terminal
      region. Thus, PLA2-I may be involved in physiologic processes which accompany the
      formation of plasmin.

PMID- 8292011
TI  - An S1 nuclease sensitive region in the PDGFA-chain gene promoter contains a
      positive transcriptional regulatory element.
AB  - Homodimers of the platelet-derived growth factor (PDGF) A-chain are strong
      mitogens for cells of mesenchymal origin and appear to be functionally important
      during development and perhaps in phenotypic transformation. In order to
      understand mechanisms of the developmental regulation of the PDGF A-chain gene
      and its dysregulation in transformation, we used S1 nuclease to identify and map
      an S1 hypersensitive region that is located 482 to 513 base pairs upstream of the
      transcription initiation site of the PDGF A-chain gene. A single nuclear protein
      binds to this site in gel mobility shift assays. This site confers a 2-3 fold
      increase in transcriptional activity when inserted into a heterologous promoter
      and analysed in transient transfection assays. The results suggest that this
      region of DNA under torsional stress locally assumes a single stranded character
      and functions to upregulate promoter activity.

PMID- 8292012
TI  - Mediation of the physiological response of platelets by interactions of spectrin
      and protein 4.1 with the cytoskeleton.
AB  - Spectrin and protein 4.1 became associated with the Triton-insoluble
      cytoskeletons during platelet activation. Inhibition of platelet activation by a
      PGI2 analogue resulted in release of the proteins from the cytoskeletons. Changes
      in subcellular distributions of the proteins preceded changes in the state of
      platelet aggregation. These results suggest that interactions of spectrin and
      protein 4.1 with the cytoskeletons are involved in mediating the physiological
      response of the platelet.

PMID- 8292013
TI  - Ferric reductases in Escherichia coli: the contribution of the haemoglobin-like
      protein.
AB  - The haemoglobin-like protein (HMP) of E. coli previously isolated as a
      dihydropteridine reductase was shown to be also a ferric citrate reductase. We
      demonstrate that, in fact, HMP is a flavin reductase and that its ferric
      reductase activity is a result of its ability to reduce free flavins. However,
      when compared to the two main ferric/flavin reductases of E. coli, i.e., the
      NAD(P)H: flavin oxidoreductase and the sulfite reductase, one can conclude that
      the contribution of HMP to iron reduction is negligible.

PMID- 8292014
TI  - The 100-kDa protein, whose phosphorylation precedes the fusion of chick embryonic
      myoblasts, is the eukaryotic elongation factor-2.
AB  - We have previously shown that Ca2+/calmodulin-dependent phosphorylation of the
      100-kDa protein dramatically increases during the early period of myoblast fusion
      and inhibition of the protein phosphorylation prevents the fusion. Here, we show
      that the protein phosphorylation occurs exclusively at Thr residue(s) and the
      purified 100-kDa protein can be ADP-ribosylated upon treatment with diphtheria
      toxin. Furthermore, the 13 N-terminal amino acid sequence of the 100-kDa protein,
      N-Val-Asn-Phe-Val-Asp-Gln-Ile-Arg-Ala-Ile-Met-Asp-Lys, exactly matches with that
      of elongation factor-2 from rat and hamster. These results indicate that the 100
      kDa protein in chick embryonic myoblasts is identical to the eukaryotic
      elongation factor-2.

PMID- 8292015
TI  - Homology of 1-aminocyclopropane-1-carboxylate synthase, 8-amino-7-oxononanoate
      synthase, 2-amino-6-caprolactam racemase, 2,2-dialkylglycine decarboxylase,
      glutamate-1-semialdehyde 2,1-aminomutase and isopenicillin-N-epimerase with
      aminotransferases.
AB  - Profile analysis showed the title enzymes to be homologous with the
      aminotransferases. 1-Aminocyclopropane-1-carboxylate synthase is closely related
      to subgroup I of aminotransferases which includes aspartate, alanine, histidinol
      phosphate, tyrosine and phenylalanine aminotransferase. 2,2-Dialkylglycine
      decarboxylase, glutamate-1-semialdehyde 2,1-aminomutase and 2-amino-6-caprolactam
      racemase are most similar to subgroup II which comprises aminotransferases with
      omega-amino acids as substrates. 8-Amino-7-oxononanoate synthase is closely
      related to both subgroup I and II, and isopenicillin-N-epimerase to subgroup IV
      with serine and phosphoserine aminotransferase. Aminotransferases and the title
      enzymes belong to a regio-specific family of evolutionarily related pyridoxal-5'
      phosphate-dependent enzymes.

PMID- 8292016
TI  - Dual role of calsequestrin as substrate and inhibitor of casein kinase-1 and
      casein kinase-2.
AB  - Calsequestrin from different muscle tissues and species has been phosphorylated
      by casein kinase-1 and casein kinase-2, in the conditions previously reported by
      Cala and Jones (J. Biol. Chem. 266, 391-398, 1991). Results indicates that rabbit
      cardiac and skeletal calsequestrin and frog skeletal calsequestrin are
      phosphorylated by both casein kinase-1 and casein kinase-2, at variance with
      chicken skeletal calsequestrin which is a poor substrate for both enzymes. We
      also observed that chicken calsequestrin is able to inhibit phosphorylation of
      cardiac calsequestrin, as well as other specific substrates, when added together
      to the assay medium.

PMID- 8292017
TI  - Transient thiol-expression and thiol disulphide cluster-receptor communications:
      a molecular basis for blastocyst-uterine interactions during implantation.
AB  - The attachment of trophoblast to uterine epithelium during implantation is an
      intricate and complex instance of cell-cell communication, the molecular aspects
      of which remain rather undefined. In this study, we screened the surface domains
      of the pre-, peri- and post implantation mouse embryos with a thiol-specific
      probe. Transient thiol-expression in peri-implantation embryos suggested their
      involvement in implantation either through disulphide bridge establishment or
      through a communication between a thiol-disulphide cluster of the blastocyst and
      a corresponding receptor of the endometrium.

PMID- 8292018
TI  - Localization of rabphilin-3A, a putative target protein for Rab3A, at the sites
      of Ca(2+)-dependent exocytosis in PC12 cells.
AB  - Rab3A/Smg 25A, a small GTP-binding protein, is highly concentrated in presynapse
      of neurons and implicated in neurotransmitter release. We have recently
      identified a putative target protein for Rab3A, isolated its cDNA, and designated
      it as Rabphilin-3A. To examine whether Rabphilin-3A as well as Rab3A is localized
      at the sites of Ca(2+)-dependent exocytosis, we investigated here localization of
      Rabphilin-3A and Rab3A in comparison with the sites of exocytosis in the
      differentiated PC12 cells. Rabphilin-3A as well as Rab3A was highly concentrated
      at the tips of the neurites where Ca(2+)-dependent exocytosis took place.
      Inversely, neither Rabphilin-3A nor Rab3A was concentrated at the tips of the
      neurites where Ca(2+)-dependent exocytosis did not take place. These results
      suggest that Rabphilin-3A as well as Rab3A constitutes a part of the machinery
      necessary for neurotransmitter release.

PMID- 8292019
TI  - Suppression of neointimal smooth muscle cell accumulation in vivo by antisense
      cdc2 and cdk2 oligonucleotides in rat carotid artery.
AB  - Deendothelializing balloon injury of rat carotid artery results in progressive
      intimal smooth muscle cell accumulation and luminal stenosis over 14 days after
      injury. We have found transient rises (approximately 3-fold maximal increases
      over the uninjured control value) of the kinase activities of both cdc2 and cdk2,
      key molecules for cell cycle progression, in the injured carotid artery along
      with the development of intimal proliferation. The topical application of the
      antisense, but not the sense, cdc2 and cdk2 phosphorothioate
      oligodeoxynucleotides dissolved in F127 pluronic gel around the freshly injured
      artery resulted in reductions of the intimal smooth muscle cell accumulation by
      47% and 55% respectively, as estimated by an intimal to medial cross-sectional
      area ratio, with concomitant decreases in cdc2 and cdk2 kinase activities. These
      results indicate that both cdc2 and cdk2 kinases are involved in intimal smooth
      muscle cell accumulation after balloon angioplasty and suggest a potential
      usefulness of the antisense cdc2 and cdk2 oligonucleotide therapy for arterial
      stenosis.

PMID- 8292020
TI  - The alpha 1-subunit of skeletal muscle L-type Ca channels is the key target for
      regulation by A-kinase and protein phosphatase-1C.
AB  - Despite the fact that the phosphorylation-mediated regulation of L-type Ca
      channels is viewed as a model of ion channel regulation, much remains to be
      learned about the protein phosphorylation and dephosphorylation reactions that
      underlie the regulation of the channels. The channel isoform most well studied
      biochemically is that expressed in skeletal muscle. The alpha 1- and beta
      subunits of this channel isoform are substrates for protein kinase A, but it is
      unknown if phosphorylation or dephosphorylation of both subunits contributes to
      altered channel properties. Here, we report experiments in which the alpha 1- and
      beta-subunits were differentially phosphorylated by protein kinase A and
      dephosphorylated by protein phosphatase 1c under conditions that led to channel
      regulation. The results suggest that the alpha 1-subunit plays a key role in the
      phosphorylation and dephosphorylation-dependent regulation of the L-type Ca
      channels from skeletal muscle.

PMID- 8292021
TI  - Molecular cloning of a cDNA coding for a region of an apoprotein from the
      'insoluble' mucin complex of rat small intestine.
AB  - The major part of rat small intestinal mucins occurs as an 'insoluble'
      glycoprotein complex unextractable in 6 M guanidinium chloride unless disulfide
      bonds are cleaved. One of the trypsin-resistant high-glycosylated domains of this
      complex (glycopeptide A) was recently isolated. We have now deglycosylated it
      with HF, injected it into rabbits and the obtained antiserum was used for
      expression cloning providing a cDNA clone (VR-1A). This clone contained an open
      reading frame of 235 amino acids composed of two regions. The deduced N-terminal
      53 amino acids included seven Cys residues and only one Ser, followed by a region
      of 182 residues with 64% Ser and Thr but devoid of Cys residues. Analysis of mRNA
      revealed a transcript of about 12 kb, identical in size to a band labelled with a
      probe based on the rat mucin-like protein (MLP/Muc2) cDNA. Pulsed-field gel
      electrophoresis of genomic rat DNA showed identical bands (380 and 500 kb) when
      blots were sequentially probed with the MLP/Muc2 probe and VR-1A. A panel of
      mouse x rat hybrids was used to localize the gene corresponding to both VR-1A and
      Muc2 to rat chromosome 1. The results strongly suggest that the 'insoluble' mucin
      complex of the rat small intestine is encoded by the Muc2 gene.

PMID- 8292023
TI  - Identification of two phosphorylation motifs in bovine osteopontin.
AB  - Fourteen phosphoserines and one phosphothreonine have been localized in a partial
      amino acid sequence of bovine milk osteopontin. Twelve of the phosphoserines are
      located in a Ser-X-Glu/Ser(P) sequence motif, suggesting that the
      phosphorylations are catalyzed by the mammary gland casein kinase. Two
      phosphoserines were found not to be located in a mammary gland casein kinase
      recognition sequence. Instead these two phosphoserines were located in the motif
      Ser-X-X-Glu which is a recognition sequence for casein kinase II. These data
      indicate that there might be more than one kinase active in the phosphorylation
      of osteopontin isolated from bovine milk. Furthermore, the serine in the cell
      binding sequence Arg-Gly-Asp-Ser was shown not to be phosphorylated.

PMID- 8292022
TI  - Activation of respiratory burst oxidase is accompanied by desensitization of
      p47phox in nucleoside-triphosphate binding along with its translocation to cell
      membrane.
AB  - A cytosolic component of human neutrophils, p47phox, potentiates respiratory
      burst oxidase translocating from cytosol to membrane upon cell stimulation. In
      this study, the nucleotide-binding ability of p47phox was examined using [32P]GTP
      dialdehyde (oGTP), [32P]oATP, and [32P]oNADPH. p47phox showed affinities for both
      oGTP and oATP that were 14 times higher than that for oNADPH, suggesting that it
      is a nucleoside triphosphate (NTP)-binding protein rather than an NADPH-binding
      protein. Binding analysis of p47phox using either [32P]oGTP or [32P]oATP revealed
      an apparent binding constant for each individual NTP analogue and the same
      maximum binding value, which suggests that both NTPs share a common specific
      binding site. Stimulation of neutrophils with phorbol myristate acetate (PMA)
      resulted in enhancement of the oxidase activity to generate O2- anion and was
      accompanied by substantial translocation of p47phox to membrane. However, p47phox
      derived from the stimulated cell membrane had lost its NTP-binding ability,
      unlike that from the resting cytosol. These results suggest that the binding of
      NTP to p47phox may be involved in the process that activates the oxidase and is
      desensitized in translocated p47phox.

PMID- 8292024
TI  - Reduced phospholipase A2 activity is not accompanied by reduced arachidonic acid
      release.
AB  - Arachidonic acid release in cells highly over expressing cytosolic phospholipase
      A2 has been attributed to mitogen-activated protein kinase phosphorylation of
      cytosolic phospholipase A2 on serine-505. To investigate the role of cytosolic
      phospholipase A2 in cellular physiology, we attempted to inhibit cytosolic
      phospholipase A2 in the intact cell employing an antisense RNA strategy. Swiss
      3T3 cells were stably transfected with an antisense cytosolic phospholipase A2
      expression vector. A clone of cells with reduced immunodetectable cytosolic
      phospholipase A2, compared to a vector transfected cell line, was identified by
      Western blotting and a corresponding decrease in phospholipase A2 activity was
      confirmed by enzymatic assay in cell free extracts. However, arachidonic acid
      release from intact cells in response to agonists was not different between
      antisense and control cell lines. Thus, arachidonic acid release in intact cells
      with decreased cytosolic phospholipase A2 activity is likely to be modulated by
      rate limiting factors that are extrinsic to cytosolic phospholipase A2.

PMID- 8292025
TI  - Conformational study on an insect neuropeptide of the AKH/RPCH-family by combined
      1H NMR spectroscopy and molecular mechanics.
AB  - Peptides of the AKH/RPCH family are mainly involved in influencing energy
      metabolism in insects, i.e., regulating carbohydrate and/or lipid breakdown in
      the fat body. We have studied the solution conformation of a member of this
      family, the peptide Emp-AKH from praying mantis. It has been characterized by use
      of two dimensional nuclear magnetic resonance spectroscopy and molecular
      modelling. The proton spectrum of the Emp-AKH peptide was assigned by sequential
      assignment procedure. Proton-proton distances were derived from the volumes of
      cross-peaks in two dimensional nuclear Overhauser enhancement spectra. The three
      dimensional structure was built using Evans & Sutherland molecular modelling
      station. Our data indicate that the Emp-AKH peptide has adopted a beta-sheet
      structure for amino acids 1 to 5 and a beta-turn for amino acids at positions 5
      to 8. The type of turn appears to be a Non-specific beta-turn.

PMID- 8292026
TI  - Occurrence of specific sterols in Pneumocystis carinii.
AB  - We have examined the sterol composition and biosynthesis of rat Pneumocystis
      carinii. We found a number of lipid components among the nonsaponifiable fraction
      that appear unique to P. carinii. These lipids are present in P. carinii purified
      preparations and P. carinii-infected whole lungs but absent from control lungs.
      They show chromatographic properties typical of sterols on GC and HPLC; they are
      present in free and esterified sterol fractions isolated by thin layer
      chromatography, they are precipitated by digitonin and they are labeled upon
      incubation of purified P. carinii cell suspensions with [3H] mevalonate and [3H]
      squalene. The finding of these sterols opens new opportunities for the
      identification of chemotherapeutic targets against P. carinii.

PMID- 8292027
TI  - Stabilization of interleukin-2 receptor alpha chain mRNA by HTLV-1 Rex in mouse L
      cells: lower amounts of Rex do not stabilize the mRNA.
AB  - T cell growth factor receptor, interleukin-2 receptor alpha chain (IL-2R alpha)
      is constitutively expressed on human T-cell leukemia virus type-1 (HTLV-1)
      infected T cells. We have established L cell lines which express both IL-2R alpha
      and the Rex protein of HTLV-1. We found that IL-1R alpha mRNA is stabilized in a
      cell line, Ltk/1-2a, which expresses a high amount of the Rex protein. In the
      presence of lower amounts of Rex, stabilization of the mRNA was not observed.
      These results may well explain the mechanism by which most of the lymphocytes
      infected with HTLV-1 escape from malignant transformation.

PMID- 8292028
TI  - Heparin-binding EGF-like growth factor is a potent mitogen for rat hepatocytes.
AB  - We examined the hepatotrophic activity of heparin-binding EGF-like growth factor
      (HB-EGF), a recently identified potent mitogen for vascular smooth muscle cells
      and fibroblasts. HB-EGF stimulated DNA synthesis of rat hepatocytes in primary
      culture in a dose-dependent manner up to 30 ng/ml. The maximal stimulation by HB
      EGF represented more than 80% of that induced by HGF. In normal rat liver, the
      transcript of HB-EGF gene was detected in the non-parenchymal cells and very low
      level in the hepatocytes. In the regenerating liver on the 3rd day after 70%
      hepatectomy, the HB-EGF mRNA increased in the non-parenchymal cells, suggesting
      that HB-EGF may contribute to liver regeneration through a paracrine mechanism.

PMID- 8292029
TI  - Interaction of a novel Tn (GalNAc alpha 1-->Ser/Thr) glycoprotein with Gal,
      GalNAc and GlcNAc specific lectins.
AB  - A naturally occurring Tn glycoprotein (Native ASG-Tn) with GalNAc alpha 1-
      >Ser/Thr as the only carbohydrate side chains, has been prepared from armadillo
      submandibular glands. In a quantitative precipitin assay, this glycoprotein
      completely precipitated Maclura pomifera (MPA), Vicia villosa B4 (VVL-B4) and
      Artocarpus integrifolia (Jacalin, AIL). It also reacted well with Helix pomatia
      (HPL) and Wistaria floribunda (WFL) and precipitated over 75% of the lectin
      nitrogen added, but poorly with Ricinus communis agglutinin (RCA1), ricin, peanut
      (Arachis hypogaea, PNA), Abrus precatorius agglutinin (APA) and Triticum vulgaris
      (WGA). This finding suggests that this novel Tn-glycoprotein may serve as a
      useful reagent for differentiating Tn and T specific monoclonal antibodies and
      lectins.

PMID- 8292030
TI  - Abnormal physical architecture of the lipophilic domains of human sperm membrane
      in oligospermia: a logical cause for low fertility profiles.
AB  - Three different domains of human sperm membrane, viz., the hydrophobic domains,
      the aqueous compartments and the surface proteins were probed to evaluate the
      molecular dynamics in these microenvironments in normal as well as oligospermic
      cases. Decreased rotational motion of the stearic spin-labels, designated rigid
      lipid matrix affording hindrance to the protein rotation in spermatozoa of
      oligospermic patients. The intrinsic tight anchoring of thiol containing proteins
      led to their increased ordering on the spermatozoa of such individuals.
      Fluorescence polarization studies revealed weaker hydrophobicity around these
      sperm proteins in oligospermia. Thus, this study identifies abnormal molecular
      mobility in the limiting membranes of oligospermic cells.

PMID- 8292031
TI  - Histatin as a synergistic stimulator with epidermal growth factor of rabbit
      chondrocyte proliferation.
AB  - Histatin 5 dose-dependently increased DNA synthesis in rabbit costal chondrocytes
      in culture. The level of DNA synthesis was stimulated by histatin 5 to about 4
      times that of the control. The combination of histatin 5 and epidermal growth
      factor (EGF) increased the DNA synthesis to about 40 times that of the control
      while EGF alone stimulated it 15-fold, indicating synergistic stimulation by both
      factors. Enzyme-linked immunosorbent assay using anti-histatin 5 demonstrated
      that human serum contained histatin-like substances. These findings suggest that
      histatins play an important role in chondrocyte proliferation, presumably as a
      physiological modulator of the action of EGF.

PMID- 8292032
TI  - Characterization of interactions of nitric oxide with human hemoglobin A by
      infrared spectroscopy.
AB  - Infrared spectra permit direct measurements of cysteine thiols as well as nitric
      oxide bound to heme iron in human hemoglobin A nitrosyl. A single symmetric N-O
      stretch band of nitric oxide bound to Fe2+ is detected amid strong water and
      protein bands in the Hb14N16O minus Hb15N16O difference spectrum. Nitric oxide
      accepts electron density from metal in bent-end-on FeI2+)-14N-16O (nu NO = 1616.5
      cm-1) and donates electron density to metal in linear Fe(3+)-14N-16O (nu NO =
      1925 cm-1). S-H stretch bands reveal that changes in protein conformation occur
      at alpha-104, beta-93, and beta-112 cysteines upon conversion of deoxyHb to HbNO
      but that no reactions of thiols with NO occur. Furthermore, no infrared band for
      S-nitrosothiol is detected. Changes in amide I spectra reflect NO binding induced
      changes in protein secondary structure.

PMID- 8292033
TI  - PDGF-induces the glutathione-dependent enzyme PGH2/PGE2 isomerase in NIH3T3 and
      pEJ transformed fibroblasts.
AB  - Exposure of NIH3T3 and pEJ serum-starved cells to platelet derived growth factor
      results in a 16 fold increase in the glutathione-dependent enzyme prostaglandin
      H2/prostaglandin E2 isomerase activity (EC 5.3.99.3). The response is rapid as a
      detectable increase in NIH3T3 cells occurs after only 7 minutes of exposure to
      the growth factor. Only a mild increase in another microsomal glutathione
      dependent enzyme, microsomal glutathione transferase (EC 2.5.1.18), was detected
      after a 2 hour exposure to the growth factor.

PMID- 8292034
TI  - The relative abundance of type 1 to type 2 cyclo-oxygenase mRNA in human amnion
      at term.
AB  - The onset of labor in humans is associated with an increase in prostaglandin
      production. One of the key steps is the conversion of arachidonic acid to
      prostaglandin E2 by cyclo-oxygenase (Cox). Cox has been found to exist as two
      distinct genes, Cox-1 and Cox-2. We have used RT-PCR to study the relative
      abundance of mRNA from each Cox gene in amnion at term. Quantitation of PCR
      efficiency indicated an approximate 100 fold excess of Cox-2 messenger RNA over
      that for Cox-1. These data point to the importance of Cox-2 in the increased
      prostaglandin synthesis associated with labor. Further studies should therefore
      focus on the control mechanisms for Cox-2.

PMID- 8292035
TI  - The interaction of calmodulin and polylysine as studied by 1H NMR spectroscopy
      and sedimentation equilibrium centrifugation.
AB  - The effects of polylysine on calmodulin were assessed using 1H NMR and
      sedimentation equilibrium centrifugation. Sedimentation equilibrium
      centrifugation measurements demonstrated that calmodulin associates with
      polylysine at calmodulin-polylysine molar ratios ranging from 10:1 to 2.5:1 and
      when polylysine is increased above the molar ratio of 1:1 a precipitate is
      formed. At a 1:2.5 calmodulin:polylysine molar ratio, 75% of the calmodulin
      precipitates from the solution and virtually no polylysine is present in the
      precipitate. 1H NMR studies of the aromatic region of calmodulin identified
      chemical shifts of three peaks at a calmodulin:polylysine molar ratio of 1:1.
      These studies suggest that polylysine associates with calmodulin in aqueous
      solution and can alter the structure of calmodulin to cause calmodulin self
      aggregation.

PMID- 8292036
TI  - cDNA cloning and chromosomal mapping of human N-acetylglucosaminyltransferase V+.
AB  - Human N-acetylglucosaminyltransferase V (GnT-V, EC 2.4.1.155) cDNA was isolated
      from a human fetal liver cDNA library. Oligonucleotide primers for polymerase
      chain reaction were designed according to the amino acid sequence of human GnT-V.
      Screening for the cDNA was carried out by plaque hybridization using PCR products
      of about 500 bp. Human GnT-V has 741 amino acids and six putative N-glycosylation
      sites. The homology to rat GnT-V is 88% at the nucleotide level and is 97% at the
      amino acid level, and there is one amino acid insertion. Using the cDNA clones as
      probe, five overlapping genomic clones have been isolated from a human phagemid
      DNA library. The GnT-V gene has been mapped to chromosome 2q21 using fluorescence
      in situ hybridization.

PMID- 8292037
TI  - Histone-induced condensation of rat testis chromatin: testis-specific H1t versus
      somatic H1 variants.
AB  - Due the likely role of H1 histone variants in inducing the formation of folded
      DNA filaments with different stabilities, the condensing capacity of the testis
      specific H1t versus the somatic variants was tested. Circular dichroism analyses
      of rat testis H1-depleted oligonucleosomes (5-2kbp) revealed that H1t, which
      appears in germ cells during the meiotic prophase of mammalian spermatogenesis,
      exerts the lowest condensing effect as compared to the other variants. The
      distribution of H1 subtypes among different chromatin fractions was also
      investigated and gave evidence that H1t is more abundant in chromatin regions
      which are more sensitive to DNAase I digestion.

PMID- 8292038
TI  - Molecular cloning and tissue specific expression of fructose 6-phosphate,2
      kinase:fructose 2,6-bisphosphatase of rat brain.
AB  - A cDNA clone (3591 base pairs) encoding an isozyme of Fructose 6-phosphate, 2
      kinase:Fructose 2,6-bisphosphatase was isolated from a rat brain cDNA library.
      The 5' sequence of this clone (1241 base pairs) was identical to that of the
      heart type isozyme cDNA (except for 7 base pair mismatches), but the 3'
      nucleotide sequence (2024 base pairs) was completely different. Its deduced amino
      acid sequence showed that the enzyme lacked a regulatory domain which contained
      phosphorylation sites for protein kinase A and C. The results of Northern
      blotting and polymerase chain reaction demonstrated that the mRNA, 7.4 kilobases
      long, was expressed also in heart, testis, liver, and skeletal muscle.

PMID- 8292039
TI  - Substituted 3-oxo-1,2,5-thiadiazolidine 1,1-dioxides: a new class of potential
      mechanism-based inhibitors of human leukocyte elastase and cathepsin G.
AB  - A series of substituted 3-oxo-1,2,5-thiadiazolidine 1,1-dioxides has been
      synthesized and their in vitro inhibitory activity toward human leukocyte
      elastase and cathepsin G was investigated. These compounds were found to
      inactivate the two enzymes efficiently and in a time-dependent fashion.

PMID- 8292040
TI  - Lactose as affinity eluent and a synthetic sulfated copolymer as inhibitor, in
      conjunction with synthetic and natural acceptors, differentiate human milk Lewis
      type and plasma-type alpha-L-fucosyltransferases.
AB  - Human milk Lewis-type (alpha 1,3/4) fucosyltransferase (FT) was separated from
      the plasma-type by chromatography on bovine IgG glycopep-Sepharose using lactose
      as the selective eluent and further purified on a column of Sephacryl S-100 HR.
      The alpha 1,3-FT activity towards 2'-fucosyllactose was found to be associated
      with alpha 1,4-FT activity. The inherency of N-acetyl-glucosaminide alpha 1,3-L
      FT activity in the Lewis-type FT was shown by a) the emergence of both alpha 1,3-
      and alpha 1,4-FT activities from the Sephacryl S-100 HR column in the same
      position; b) the inhibition of the alpha 1,3-FT activity in the Lewis-type FT by
      alpha 1,4-FT specific inhibitor namely a copolymer from 3-sulfoGal beta 1,3GlcNAc
      beta-O-Allyl and acrylamide; c) the inhibition of alpha 1,4 activity in the Lewis
      type FT by alpha 1,3-FT specific acceptor. Fetuin triantennary sialoglycopeptide,
      the corresponding asialo glycopeptide, and bovine IgG diantennary glycopeptide
      served as acceptors for both FTs, the Lewis-type FT being far more active than
      the plasma type FT towards the triantennary sialoglycopeptide.

PMID- 8292041
TI  - Attenuation of human leukocyte adherence to endothelial cell monolayers by
      tyrosine kinase inhibitors.
AB  - Expression of cell adhesion molecules is controlled by various cytokines
      including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha), but
      the underlying mechanisms are not clear. In this study, we investigated the role
      of tyrosine phosphorylated proteins in the regulation of leukocyte adhesion to
      endothelial cells. We examined the effect of genistein and herbimycin-A,
      selective inhibitors of tyrosine kinase, on the adherence of human blood
      neutrophils, lymphocytes, and monocytes to monolayers of human umbilical vein
      endothelial cells. Both genistein and herbimycin A significantly inhibited IL-1
      and TNF alpha-induced upregulation of neutrophils (p < 0.05) and monocyte (p <
      0.01) adherence. IL-1 and TNF alpha-stimulated lymphocyte adherence was
      diminished in the presence of herbimycin A (p < 0.05), but genistein only
      inhibited TNF alpha-stimulated adherence. There was no significant effect of
      genistein on IL-1-induced lymphocyte adherence. These novel findings reveal for
      the first time that tyrosine phosphorylated proteins may regulate leukocyte
      adherence and cell adhesion molecule expression on the endothelium.

PMID- 8292042
TI  - Dynamic of alpha-1-adrenoceptor mediated degradation of membrane phospholipids in
      cultured rat cardiomyocytes.
AB  - In many cell types, agonists can stimulate both phosphoinositide (PtdIns) and
      phosphatidylcholine (PC) hydrolysis by activating specific phospholipases. Using
      cultures of neonatal rat cardiomyocytes we have verified the existence of an
      alpha 1-adrenoceptor mediated hydrolysis of PtdIns and PC. PtdIns breakdown,
      evaluated as inositol phosphate production, occurred in the early phase of cell
      stimulation, while PC hydrolysis, evaluated as choline metabolite production, was
      evidenced at longer stimulation times. The appearance of a delayed peak of
      choline phosphate and the invariance of free choline in the intracellular water
      phase strongly suggest the involvement of a specific PC-phospholipase C,
      generating choline phosphate and diacylglycerol, the activator of protein kinase
      C. Since it is plausible that various metabolites of signal-induced degradation
      of membrane phospholipids may take part in long term physiological responses, PC
      breakdown could be involved in cellular mechanisms that require prolonged protein
      kinase C activation.

PMID- 8292043
TI  - Carboxyl methylation of protein phosphatase 2A from Xenopus eggs is stimulated by
      cAMP and inhibited by okadaic acid.
AB  - Protein phosphatase 2A is the principal carboxyl methylated protein in
      cytoplasmic extracts derived from Xenopus eggs arrested in interphase. Levels of
      methylation approach stoichiometric values after 2 hr of incubation at 22 degrees
      C. Rates of PP2A methylation increase by over 50% upon addition of cAMP.
      Methylation is inhibited by okadaic acid at concentrations that inhibit PP2A
      phosphatase activity.

PMID- 8292044
TI  - Angiotensin converting enzyme and genetic hypertension: cloning of rat cDNAs and
      characterization of the enzyme.
AB  - Using genetic mapping approaches, a gene on chromosome 10, Bp1, has been
      identified in the stroke-prone spontaneously hypertensive rat (SHRSP) in the same
      region that contains the gene for angiotensin converting enzyme (ACE). Since ACE
      plays an important role in blood pressure regulation, the ACE gene is a leading
      candidate for Bp1. To examine the possibility that a structural abnormality of
      ACE exists in the SHRSP, we cloned and characterized the cDNAs for the Wistar
      Kyoto rat (WKY) and SHRSP ACE. Both cDNAs encode a single polypeptide of 1,313
      amino acid residues with an estimated molecular weight of 150.9 KDa. Five
      nucleotide differences were identified between the WKY and the SHRSP ACE cDNAs.
      One of these differences resulted in an amino acid substitution (Lys-207 in the
      WKY to Arg-207 in the SHRSP). But the enzymatic properties of partially purified
      ACE from the two strains were similar. Thus the data suggest that an alteration
      in the primary structure of rat ACE does not contribute to the hypertension in
      the SHRSP.

PMID- 8292045
TI  - Evidence for the presence of topoisomerase like activity in mitochondria of
      Saccharomyces cerevisiae.
AB  - During studies on the enzymology of DNA replication in mitochondria of
      Saccharomyces cerevisiae, a topoisomerase like activity was detected for the
      first time. Crude extracts of mitoplast were found to show enzyme activities
      which could both catenate and relax supercoiled plasmid DNA. Chromatography of
      the mitoplast lysate on a phosphocellulose column, using Tris-HCl (pH 7.5) buffer
      containing 0.6 M NaCl as eluent, was found to yield a topoisomerase like activity
      capable of relaxing supercoiled plasmid DNA (Fraction 1). This fraction was not
      dependent on ATP for its activity. The other fraction eluting at 1M NaCl showed
      predominantly catenating activity, which was found to be ATP dependent.

PMID- 8292046
TI  - Annetocin: an oxytocin-related peptide isolated from the earthworm, Eisenia
      foetida.
AB  - An oxytocin-vasopressin-related peptide, Cys-Phe-Val-Arg-Asn-Cys-Pro-Thr-Gly-NH2,
      was isolated from the lumbricid earthworm, Eisenia foetida and termed annectocin.
      Annetocin potentiated not only spontaneous contractions of the gut but also
      pulsatory contractions and bladder-shaking movement of the nephridia. Annetocin
      may be involved in osmoregulation of the animal through nephridial function.

PMID- 8292047
TI  - An upper limit for the effect of 60 Hz magnetic fields on bioluminescence from
      the photobacterium Vibrio fischeri.
AB  - Bioluminescence from Vibrio fischeri was measured in the presence and absence of
      60 Hz magnetic fields. The peak value of the field was approximately 1.3 mT, a
      value approximately 13 times the Earth's background static field and comparable
      to the AC field near heavy-duty electrical equipment such as generators. The
      objective of this work was a search for causality between the applied magnetic
      field and a basic biological function at the biochemical, membrane or cellular
      level based on the direct linkage of bioluminescence to many of the cells
      mandatory functions such as enzyme (luciferase) activity, electron transport,
      proton translocation, iron uptake, oxidative metabolism, and cellular
      communication via the autoinducer N-[3-oxohexanoyl] homoserine lactone. A
      variation in the activity of any one of these functions will cause a change in
      bioluminescence. The key result of this work is that, for a signal to noise ratio
      of 1:1, an effect, if present at all, must be less than 1% of the baseline level
      of continuously monitored bioluminescence.

PMID- 8292048
TI  - Rapid desensitization of agonist-induced calcium mobilization in transfected PC12
      cells expressing the rat neurotensin receptor.
AB  - The effect of neurotensin on intracellular calcium mobilization was measured in
      PC12 cells transfected with the cDNA sequence encoding the rat neurotensin
      receptor. Stimulation with nanomolar concentrations of neurotensin induced a
      rapid increase of the [Ca++]i. This response was transient and the [Ca++]i
      returned to basal level within 2 minutes, despite the continuous presence of the
      agonist. The response was also observed in the absence of extracellular calcium,
      indicating the intracellular origin of the released calcium. Successive
      stimulations with the same concentration of the peptide failed to produce similar
      responses. ATP was also found to mediate the release from the same intracellular
      store of calcium in PC12 cells. The amplitude of the response to ATP was not
      affected by previous stimulation with neurotensin. These results demonstrate the
      existence of a rapid and homologous desensitization of the neurotensin-induced
      calcium release in PC12 transfected cells.

PMID- 8292049
TI  - Regulation of alternative pathway complement activation by glycosaminoglycans:
      specificity of the polyanion binding site on factor H.
AB  - The discrimination between activators and nonactivators of the alternative
      pathway of complement depends on the affinity of the control factor H for C3b
      molecules covalently associated with the target. The affinity of factor H for the
      C3b-target complex is regulated by a positively charged site at or near the 13th
      short consensus repeat (SCR) domain of factor H. In this study we have analyzed
      the ability of different glycosaminoglycans and other negatively charged
      macromolecules to interact with the factor H polyanion recognition site and to
      enhance binding of H to the C3b-target complex. Strongest enhancement of factor H
      binding to zymosan-C3b was observed by the highly sulphated glycoconjugates
      dextran sulphate (m.w. = 5,000), heparin, chondroitin sulphate A and carrageenan
      (types III and IV). DNA also enhanced H binding. Removal of N-linked sulphates or
      reduction of the size of heparin decreased its enhancing effect on H binding.
      Little or no effect was seen with chondroitin sulphate C, keratan sulphate,
      hyaluronic acid, colominic acid (bacterial polysialic acid) or negatively charged
      polypeptides. The results show that the interaction of the polyanion binding site
      on factor H with glycosaminoglycans depends upon the number, orientation and
      polymeric arrangement of sulphate groups and suggest that most, but not all,
      sulphated glycosaminoglycans participate in the protection of host tissues from
      complement damage by promoting inactivation of tissue-bound C3b.

PMID- 8292050
TI  - p56lck phosphorylation by Ca2+/calmodulin-dependent protein kinase type II.
AB  - Ca2+/calmodulin-dependent protein kinases are implicated in regulating the Ca2+
      signaling involved in T cell activation and in thymocyte selection. One of the
      earliest events in signaling through the T cell antigen receptor is activation of
      the protein tyrosine kinase p56lck. Following T cell activation or signaling
      through the IL-2 receptor, Ca(2+)-mediated phosphorylation of p56lck occurs on
      serine/threonine residues. Isoforms of the multifunctional Ca2+/calmodulin
      dependent protein kinases, CaM kinase-II and CaM kinase-Gr are found in human T
      lymphocytes. CaM kinase-II, but not CaM kinase-Gr, phosphorylates the T cell
      tyrosine kinase p56lck in vitro. Tryptic phosphopeptide maps indicate that CaM
      kinase-II phosphorylates p56lck on multiple sites in vitro. Kinase assays of
      p56lck modified by CaM kinase-II indicate that CaM kinase-II modification does
      not appreciably affect p56lck phosphotransfer activity.

PMID- 8292051
TI  - Microsatellite mutation (CAG24-->18) in the androgen receptor gene in human
      prostate cancer.
AB  - The androgen receptor (AR) gene contains a polymorphic CAG microsatellite that
      codes for a variable length of glutamine repeats in the AR protein.
      Microsatellite DNA sequences may be potential sites of genetic instability. Using
      the polymerase chain reaction (PCR), we screened 40 human prostate cancer
      specimens for expansions or deletions of this microsatellite. In one patient,
      nontumor DNA yielded a single PCR product, as expected for the AR, but the tumor
      DNA yielded two discrete products, one identical to normal, and a second smaller
      one. Direct sequencing revealed that the nontumor tissue contained 24 CAGs,
      whereas the tumor contained one fragment with 24 CAGs (wild-type) and a second
      fragment with 18 CAGs (mutant), representing a somatic contraction of the AR CAG
      repeat (CAG24-->CAG18) in the tumor. Interestingly, this patient manifested a
      paradoxical agonistic response to hormonal therapy with the antiandrogen
      flutamide.

PMID- 8292052
TI  - Stimulatory effect of IL-1 beta on catecholamine secretion from cultured bovine
      adrenal medullary cells.
AB  - We investigated the effect of recombinant human interleukin-1 beta (IL-1 beta) on
      catecholamine secretion from cultured bovine adrenal medullary cells. Treatment
      of cultured cells with IL-1 beta (10 ng/ml) for 24 hr caused an increase in
      accumulation of catecholamines in the cultured medium. The accumulation of
      catecholamines stimulated by IL-1 beta was observed in time (4-48 hr)- and
      concentration (3-30 ng/ml)-dependent manners. The stimulatory effect of IL-1 beta
      (10 ng/ml) was completely inhibited by recombinant human IL-1 receptor antagonist
      (1 microgram/ml). IL-1 beta had little effect on [3H]norepinephrine uptake to
      cultured cells. These results suggest that IL-1 beta stimulates catecholamine
      secretion through activation of IL-1 receptors in adrenal medullary cells.

PMID- 8292053
TI  - The association between CD45 and lck does not require CD4 or CD8 and is
      independent of T cell receptor stimulation.
AB  - CD45, the major transmembrane tyrosine phosphatase of lymphoid cells, is required
      for optimal signaling via a number of receptors. A model for how CD45 regulates
      signaling is that it controls phosphorylation of the COOH-terminal tyrosine of
      src family kinases. We have shown that CD45 physically associates with lck, one
      src kinase. Others have shown that CD45 also interacts with the CD4 and CD8
      surface antigens expressed on many T cells. In this report we examine further the
      relationship between CD45 and lck in a CD4+ T cell line and in peripheral T
      cells. We show now that CD45 associates with lck independently of both CD4 and
      CD8. We show also the time course of an association between CD45 and a form of
      lck that migrates at an apparent higher molecular mass. Finally, we demonstrate
      that the interaction between CD45, lck, and a previously reported 32-34 kD
      protein is stable after stimulation of T cells.

PMID- 8292054
TI  - Interactions between growth hormone and nutrition in hypophysectomised rats:
      skeletal muscle myosin heavy chain mRNA levels.
AB  - The aim of this study was to examine the role of growth hormone (GH) in
      regulating muscle phenotype and to determine how this is modulated by altered
      nutrition. Total RNA was extracted from gastrocnemius muscles of
      hypophysectomised rats treated with saline, GH or GH but fed a restricted intake.
      Type 1, 2A, 2B, embryonic and neonatal myosin heavy chain mRNA levels were
      estimated by slot blot hybridization. Hypophysectomy reduced the concentrations
      of types 1, 2A and embryonic mRNAs and dramatically elevated types 2B and
      neonatal compared to control levels, but this was time-dependent. All MHC mRNA
      levels were partially restored to control levels in the GH-treated rats except
      for type 1; the level of this transcript was only elevated by GH in the
      restricted intake group. Restricted food intake modulated the effects of GH
      administration for all other MHC mRNA concentrations.

PMID- 8292056
TI  - Pattern of interaction between dihydropyridine calcium antagonists and cationic
      amphiphilic drugs in isolated guinea-pig left atria.
AB  - The pharmacodynamic interaction between dihydropyridine calcium antagonists and
      several cationic amphiphilic agents with respect to their negative inotropic
      action has been studied in isolated guinea-pig left atria. (+/-)-Bepridil (CAS
      64706-54-3), (+/-)-cis-diltiazem (CAS 33286-22-5), falipamil (CAS 77862-92-1),
      (+/-)-gallopamil (CAS 16662-47-2), lidocaine (CAS 6108-05-0), procainamide (CAS
      614-39-1), or quinidine (CAS 50-54-4) were added at fixed concentrations.
      Afterwards, concentration-response curves for nifedipine (CAS 21829-25-4), the S
      enantiomer niguldipine.HCl and its R-enantiomer dexniguldipine.HCl (CAS 113165-32
      5), (+/-)-nimodipine (CAS 66085-59-4) (+/-)-nitrendipine (CAS 39562-70-4), or (+/
      )-isradipine (CAS 75695-93-1) were obtained. In most cases, a left-ward shift in
      the concentration-response curve of the dihydropyridine was observed. The extent
      of this shift varied between dihydropyridines, and it depended on the
      catamphiphilic compound present. A high correlation was found between the
      different dihydropyridines, when comparing the extent of displacement of their
      concentration-response curves by the various catamphiphilic test compounds.
      Although quantitative differences exist between the different dihydropyridines,
      they are affected in potency by other compounds with a rather similar pattern.
      Accordingly, some general predictions about the interactions of a given
      dihydropyridine might be possible using limited datasets.

PMID- 8292055
TI  - Interference of N-(1-[4-(4-fluorophenoxy)butyl]-piperidinyl)-N-methyl- 2
      benzothiazolamine with Na+/H+ exchange and Na+/Ca2+ exchange in purified cardiac
      sarcolemmal membranes.
AB  - The effect of R 56865 (N-[1-[4-(4-fluorophenoxy)butyl]-piperidinyl]-N-methyl-2-
      benzothiazolamine, CAS 104606-13-5) on Na+/H+ exchange and Na+/Ca2+ exchange was
      studied in isolated cardiac sarcolemmal vesicles. R 56865 inhibited Na+/H+
      exchange with an ED50 of 180 mumol/l at a concentration of 0.05 mmol/l Na+. The
      potency of R 56865 decreased with increasing concentrations of Na+. Na+/Ca2+
      exchange was also inhibited. The ED50 amounted to 45 mumol/l. This ED50 was close
      to that of the reference compound dichlorobenzamil (ED50 = 27 mumol/l). The
      inhibitory potency of R 56865 on Na+/H+ and Na+/Ca2+ exchange is far too low to
      explain the already reported beneficial effects of this inhibitor of Na+ and Ca+
      overload during ouabain intoxication and ischemia and reperfusion.

PMID- 8292057
TI  - Effect of a new calcium antagonist on hemodynamics at rest and exercise loading
      in patients with essential hypertension.
AB  - MPC-1304 ((+-)-methyl 2-oxopropyl 1,4-dihydro 2,6-dimethyl-4-(2-nitrophenyl)-3,5
      pyridinedicarboxylate, CAS 86780-90-7), a new calcium antagonist, was orally
      administered to 10 outpatients with mild essential hypertension. It was observed
      that MPC-1304 inhibited elevations of blood pressure both at rest and under
      exercise loading without any adverse hemodynamic effects. The findings obtained
      indicated that MPC-1304 would be clinically useful in the treatment of
      hypertensive patients undergoing therapy while continuing normal everyday
      activities including physical exertion.

PMID- 8292058
TI  - Imidazole based non-peptide angiotensin II receptor antagonists. Investigation of
      the effect of the orientation of the imidazole ring on biological activity.
AB  - Non-peptide angiotensin II receptor antagonists related to losartan (DuP 753, CAS
      114798-26-4) were prepared and evaluated for antagonist activity in the rat
      isolated uterus assay. The synthetic strategy concentrated on changes in the
      orientation of the imidazole ring relative to the substituents, which were
      maintained in a similar pattern to that found in losartan. The results indicate
      that biological activity of such antagonists shows little dependence on the
      orientation of the imidazole ring, but that the spacing of the substituents of
      primary importance.

PMID- 8292059
TI  - General pharmacology of the non-sulfhydryl angiotensin converting enzyme
      inhibitor N-[8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline.
AB  - The effects of N-[8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline (AB-47, CAS
      120008-53-9), an orally active angiotensin converting enzyme inhibitor, on the
      central nervous, respiratory and cardiovascular, autonomic systems, isolated
      smooth muscles and other functions were investigated in various experimental
      animals. AB-47 had no effect on central nervous, autonomic systems and isolated
      smooth muscles. AB-47 (10 and 30 micrograms/kg i.v.) significantly lowered
      femoral blood pressure without affecting respiration and heart rate in
      anesthetized rats. However, AB-47 had no effect on the contractile tension of
      mammalian isolated atrium and aorta. AB-47 had no effect on gastrointestinal
      transit in mice. Very slight injury of gastric mucosa was observed 4 h after the
      oral administration of AB-47 in rats but AB-47 did not damage the small
      intestinal mucosa. AB-47 had no effect on the contraction of rat phrenic nerve
      diaphragm preparation induced by electrical stimulation. AB-47 did not affect the
      incidence of acetic acid-induces writhings. AB-47 potentiated carrageenan-induced
      hind paw edema in rats. The potentiation of edema may be due to an accumulation
      of bradykinin induced by the inhibition of angiotensin converting enzyme (ACE),
      because ACE is the identical enzyme with kinase II. The pretreatment of AB-47 for
      7 days (1, 3, 10 mg/kg/d p.o.) inhibited the cardiac hypertrophy induced by
      isoproterenol (isoprenaline). This result suggests that the renin-angiotensin
      aldosterone system directly or indirectly participates in the cardiac hypertrophy
      induced by isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292060
TI  - New pyridazino[4,5-b]indole derivatives with inodilator and antiaggregatory
      activities.
AB  - Some 4-(3,5-dimethylpyrazol) 5H-pyridazino [4,5-b]indoles (7), 1,2,4-triazolo
      [4,3-b]pyridazino [4,5-b]indoles (9) and 1,2,4-tetrazolo [4,5-b]pyridazino [4,5
      b] indoles (11) substituted in position 1 by amino groups have been synthesized
      and tested as inotropic agents and inhibitors of platelet aggregation. 6
      Imidazolyl-11H-1,2,4-triazolo [4,3-b]pyridazino [4,5-b]indole (9) shows an
      activity superior to that of amrinone, with a notable selectivity towards
      phosphodiesterase (PDE) IV and PDEV, vasodilator activity and a good effect on
      blood platelet aggregation.

PMID- 8292061
TI  - [Evaluation of the bioequivalence of two fast-releasing iron(II) sulfate
      formulations].
AB  - Bioequivalence of a new oral iron formulation (A: FE(II)SO4.H2O, capsule with 100
      mg Fe++, Eryfer 100, CAS 7782-63-0) with the standard formulation (B:
      Fe(II)SO4.H2O, capsule with 50 mg Fe++, Eryfer) was demonstrated after
      administration of 100 mg Fe++ in a single-dose two-way cross-over design to 16
      normal female volunteers. Iron concentrations were monitored from 24 h before
      (basal) to 24 h post application. The area under concentration difference curve
      AUC(diff) and the maximal concentration difference Cmax(diff) were calculated
      subtracting the basal from the time-corresponding postabsorptive concentrations.
      AUC(diff) (A: 170 nmol/ml. h, B: 168 nmol/ml.h) and Cmax(diff) (A: 23.3 nmol/ml,
      B: 21.8 nmol/ml) showed but minor differences between formulations. The AUC(diff)
      and Cmax ratio (A/B) and the corresponding 90% confidence intervals, 102% (74
      129%) and 107% (91-123%), were included by the acceptance range of 70-130% as
      stated in the study protocol. Hence, both formulations were bioequivalent with
      respect to rate and extent. The ANOVA coefficient of variation of Cmax(diff) was
      considerably smaller than that of AUC(diff) (26% versus 44%). The characteristics
      based on the postabsorptive iron increase (post-absorptive concentrations minus
      concentration preceding immediately application) AUC(pad) (ratio 99% (83-114%)
      and Cmax(pad) (ratio 104% (95-112%) exhibited smaller ANOVA-CVs (25% and 14%,
      respectively) as compared with AUC(diff) and Cmax(diff). All these
      characteristics appeared to be rather normal than log-normal distributed. It was
      concluded that the study design was selective to demonstrate an adequate
      bioavailability of iron formulations.

PMID- 8292062
TI  - [Pharmacokinetics of colloidal bismuth subcitrate. Solution versus tablet].
AB  - The aim of the present study was the investigation of the pharmacokinetics of
      bismuth after application of different preparations of colloid bismuth subcitrate
      (CBS; CAS 57644-54-9). 6 healthy volunteers were recommended to take a solution
      containing 240 mg CBS b.d. before breakfast and before the evening meal for 2
      weeks, whereas 6 other volunteers received tablets containing 120 mg CBS 2 b.d.
      In both groups resulting daily CBS dose was 480 mg. On day 7 and day 14, 24 h
      urine excretion of bismuth was found to be significantly lower after application
      of the solution as compared to the one after application of the tablet (day 7:
      solution 110 micrograms/day--table 872 micrograms/day; day 14: solution 133
      micrograms/day--table 872 micrograms/day; p < 0.05). After a single dose of 240
      mg of CBS plasma AUC amounted to 42.8 micrograms/ml.h and 4.2 micrograms/ml.h
      after application of the tablet and the solution, respectively. Our results
      demonstrate that systemic bismuth load is markedly lower after application of the
      CBS solution as compared to the CBS tablet.

PMID- 8292063
TI  - Pharmacodynamic dose finding of dimetindene in a sustained release formulation.
AB  - A sustained release form of dimetindene (dimethindene maleate, Fenistil, CAS 3614
      69-5) was developed based on a micropellet technique. Aim of the study was to
      evaluate the efficacy and duration of two doses of dimetindene in a sustained
      release pellet formulation with a standardised grass pollen provacation model
      (Vienna Challenge Chamber; VCC). The study with 12 grass pollen allergic
      volunteers--verified by case history, skin prick test (SPT), and radio allergo
      sorbent test (RAST)--was carried out in a placebo controlled, double blind, cross
      over design. 12 h before a 4-h-lasting continuous challenge with permanent 1000
      dactylis grass pollen in the VCC, administration of dimetindene (Fenistil R
      Pellets) in doses of 4 mg, 8 mg or identically appearing placebo was scheduled in
      three sessions. Nasal flow and resistance, nasal secretion and subjective
      symptoms were recorded at 15-min intervals during this long-term challenge under
      reproducible conditions. In comparison to placebo, dimetindene leads to a
      statistically significant reduction (p < 0.05) of nasal response and clinical
      symptoms for at least 16 h after treatment. The efficacy of 8 mg dimetindene was
      pronounced over 4 mg, however, the differences between both active treatments
      were not statistically significant. Therefore 4 mg dimetindene once a day is the
      adequate treatment for usual pollinotic disease conditions.

PMID- 8292064
TI  - Comparative study of the efficacy and safety of loratadine syrup and terfenadine
      suspension in the treatment of chronic allergic skin diseases in a pediatric
      population.
AB  - The safety and efficacy of loratadine (Sch 29851, CAS 79794-75-5) syrup (5 or 10
      mg QD) was compared to terfenadine (CAS 50679-08-8) suspension (30 mg b.i.d.) in
      a randomized, third party blind, parallel-group, multicenter trial. Two hundred
      thirty-six children ages 6-12 years, with chronic allergic skin disorders were
      treated for 14 days. The predominant skin condition was atrophic dermatitis (88%
      of the efficacy population). Evaluation of efficacy was based on investigator and
      patient assessment of symptoms, overall condition of the disease, and therapeutic
      response to treatment. After 7 and 14 days of treatment, and in the endpoint
      analysis (last valid study visit for all patients) the decreases from baseline in
      mean total sign/symptom scores, and all individual symptoms, did not differ
      significantly (p > 0.05) between treatments. Itching improved 54% in the
      loratadine group and 58% in the terfenadine group in the endpoint analysis. Forty
      five percent of patients treated with loratadine and 46% of terfenadine-treated
      patients treated had complete or marked relief of their symptoms at endpoint. The
      efficacy of loratadine increased during the study, suggesting that patients did
      not develop tolerance to the medication over the 14-day course of therapy. Mild
      to moderate treatment-related adverse experiences were reported in 7/113 patients
      (6%) treated with loratadine and 11/119 patients (9%) treated with terfenadine.
      Single daily doses of 5 mg or 10 mg loratadine syrup were comparable to
      terfenadine suspension 30 mg twice daily for improving the symptoms of chronic
      allergic skin disorders in children. Loratadine was safe and well tolerated.

PMID- 8292065
TI  - Validity of saliva samples for the estimation of dipyrone metabolites
      pharmacokinetics.
AB  - Plasma and saliva pharmacokinetics of dipyrone (CAS 5907-38-0) metabolites, 4
      methylaminoantipyrine (MAA), 4-aminoantipyrine (AA), 4-formylaminoantipyrine
      (FAA) and 4-acetylaminoantipyrine (AAA), has been studied in 10 healthy
      volunteers, after oral administration of 1.0 g dipyrone, MAA, AA, FAA and AAA
      saliva concentrations correlated significantly with the respective plasma
      concentrations (r = 0.81, r = 0.62, r = 0.83 and r = 0.91, p < 0.001). MAA and AA
      concentrations in saliva were lower than in plasma while the FAA and AAA saliva
      concentrations were similar to the respective plasma concentrations. The
      saliva/plasma concentration ratios were highly dependent on sampling time. The
      elimination half-life of the final metabolites FAA and AAA can be equally
      evaluated from plasma and saliva data. For MAA, plasma and saliva t1/2 values
      were significantly correlated despite a substantial intra-subject difference. No
      correlation was found for AA plasma and saliva derived pharmacokinetic
      parameters. Similar to the plasma AAA/AA ratio, the saliva AAA/AA ratio in spot
      sample 6 h following oral dose might be proven to be a reliable discriminatory
      index for acetylation phenotyping.

PMID- 8292066
TI  - Comparative pharmacokinetic evaluation of compressed naproxen suppositories in
      humans.
AB  - Compressed naproxen (CAS 22204-53-1) suppositories (250 mg) were formulated by
      dispersing the drug in molten polyethylene glycol 4000 followed by congealing and
      pulverizing the mass into granules and then compressing into suppositories. Their
      pharmacokinetic performance was evaluated and compared with that of a standard
      naproxen tablet in 12 healthy human volunteers. There were no statistically
      significant (p > 0.05) differences in Cmax, tmax, t1/2, AUC and mean residence
      time (MRT) observed after oral and rectal administration of tablet and
      suppository, respectively. The relative rectal bioavailability of naproxen from
      the compressed suppositories was 96.7 +/- 2.6%. Pharmacokinetics of naproxen
      after oral and rectal administration was highly comparable.

PMID- 8292067
TI  - [Biological availability of gastric juice-resistant coated diclofenac
      preparations. 1. Bioavailability study following a single administration of a
      multiple-unit formulation in comparison with a single-unit formulation].
AB  - Bioavailability Study of Enteric Coated Diclofenac Formulations/1st
      Communication: Bioavailability study following single-dose administration of a
      multiple-unit formulation compared with a single-unit formulation Relative
      bioavailability of diclofenac (CAS 15307-86-5) was investigated after single-dose
      administration of an enteric coated multiple-unit formulation (Diclo-Puren 50,
      test) in comparison to a single-unit dosage form (reference). The study was
      carried out in a three-way changeover design with a group of 18 healthy male
      volunteers. Diclofenac plasma concentrations were measured using a selective and
      sensitive GLC-MS method after liquid-liquid extraction and subsequent
      derivatisation. Area under the curve (AUC) and maximum plasma concentrations
      (Cmax) were evaluated as pharmacokinetic characteristics. Moreover, time of
      maximum plasma concentration (tmax), lag-time (tlag) and plateau time of
      concentrations above minimum effective concentrations (MEC) of 50 ng/ml
      (tMEC(50)) and 100 ng/ml (tMEC(100)), respectively were calculated.
      Bioequivalence concerning AUC and Cmax was assessed by calculating 90%-confidence
      intervals using parametric (ANOVA, ANOVAlog) and non-parametric (Mann-Whitney)
      methods. Due to the inclusion rule bioequivalence was accepted if one of the
      calculated intervals was completely in the range of 80 to 125% (AUC) and 70 to
      143% (Cmax). tmax, tlag and tMEC were evaluated considering the differences of
      mean values. Individual plasma profiles of diclofenac are more homogeneous after
      administration of the test formulation than after administration of the reference
      product. Mean relative bioavailability of the test formulation was calculated as
      99%. Maximum plasma concentrations (mean +/- SD) were determined as 1159 +/- 632
      ng/ml (test) and as 1481 +/- 637 ng/ml (reference). Maximum plasma concentrations
      (mean +/- SD) occurred 1.4 +/- 0.7 h (test) and 1.8 +/- 0.7 h (reference) after
      administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292068
TI  - Observer-blind study with metamizole versus tramadol and butylscopolamine in
      acute biliary colic pain.
AB  - To investigate the combined analgesic and spasmolytic effect of metamizole
      (dipyrone, Novalgin, CAS 68-89-3) this drug was compared with an opioid analgesic
      (tramadol) and a pure spasmolytic drug (butylscopolamine). In a multicentre,
      observer-blind, parallel-group study conducted in five German centres 74 patients
      suffering from "severe" or "excruciating" colic pain caused by a calculus in the
      bile duct were randomized to receive intravenously 2.5 g metamizole (25
      patients), 100 mg tramadol (25 patients), or 20 mg butylscopolamine (24
      patients). The three treatment groups were homogeneous for age, sex, height,
      weight and baseline pain intensity. Metamizole was significantly more effective
      in reducing pain than tramadol and butylscopolamine for the primary endpoint,
      pain intensity on a visual analogue scale (VAS) when evaluated as the area under
      the curve (AUC) from baseline to onset of analgesic action (p < 0.05) and the sum
      of pain intensity differences (SPID) for the observation period of 2 h (p <
      0.005). The mean time until the onset of analgesic action occurred was shortest
      (p < 0.005) for metamizole (10.9 +/- 5.8 min) compared with tramadol (15.8 +/-
      11.7 min) and butylscopolamine (25.6 +/- 24.3 min). Metamizole was also more
      effective for the secondary efficacy endpoint, pain intensity on a 5-point
      ordinal scale. In the patient's overall assessment of treatment efficacy at the
      end of the trial, metamizole was rated as the most effective drug (p < 0.005).
      Fewer patients in the metamizole (3) and the tramadol (1) groups than in the
      butylscopolamine group (8) needed a second injection of the "rescue" medication
      (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292069
TI  - In vitro effects of mistletoe extracts and mistletoe lectins. Cytotoxicity
      towards tumor cells due to the induction of programmed cell death (apoptosis).
AB  - The in vitro effects of therapeutically administered mistletoe extracts
      (ABNOBAviscum) and pure mistletoe lectins (mainly mistletoe lectin I) on a
      variety of human and murine tumor cell lines have been investigated. Mistletoe
      extracts and purified mistletoe lectins inhibited in vitro the growth of all
      tumor cell lines tested including B cell hybridomas, P815, EL-4, Ke37, MOLT-4 and
      U937. The mechanism of growth arrest was shown to be due to the induction of
      programmed cell death (apoptosis). Thus, fragmentation of genomic DNA into
      oligonucleosomal bands of approximately 200 base pairs in length was observed
      within 20 h when tumor cells were incubated with mistletoe extracts or lectins.
      These data point to a rational basis for the direct cytotoxic effects of
      mistletoe extracts and lectins apart from the postulated immunostimulatory
      properties of these agents.

PMID- 8292070
TI  - Effect of drug transit time between exchange locus with plasma and sampling site.
AB  - In pharmacokinetic models used to describe the behavior of drugs in living
      organisms, generally neither the amount of drug flowing in pipes between
      compartments nor the transfer delay between the plasma-lymph exchange areas and a
      site of measurement are taken into account. Several former publications dealt
      with exchanges between two or more different organs assuming that the blood flow
      was constant or that the variation of the lymphatic flow was negligible or noting
      that the amount of drug present in pipes was not easily taken into account. In
      this article, we deal with concentration in a site of interstitial exchanges with
      regard to concentration in a sampling site with a varying blood flow, assuming
      that the transit time depends both on the fluid flow and the path length through
      pipes. In all considered cases, the plasma concentration profile may be highly
      altered by a change in the flow rate.

PMID- 8292071
TI  - Nonrenal clearance and tubular load in renal failure.
AB  - Twelve studies on the pharmacokinetics of various antibiotics (11 beta-lactams, 1
      quinolone) in renal failure were re-examined on a meta-level. It was found that
      besides the expected (and obvious) decrease of renal clearance in impaired renal
      function, the nonrenal clearance (CLNR) also decreased: in terminal renal
      insufficiency, CLNR was approximately only half the value found in healthy
      subjects. A possible explanation for this could be the uremic intoxication and
      the resulting disturbance of the metabolic processes. Though the absolute value
      decreases, nonrenal clearance in renal failure is a relevant part of the total
      elimination: the ratio nonrenal to total elimination doubled and was even more.
      Furthermore, the amount of substances eliminated per nephron was found to
      increase. The ratio "renal clearance/glomerular filtration rate", the tubular
      load, increased as well. This might have positive effects (exceptionally high
      concentrations of antibiotics at important sites in kidney infections) but also
      negative consequences (higher tubular toxicity depending on the concentration).

PMID- 8292072
TI  - Mammalian cell cultures. Part II: Genetic engineering, protein glycosylation,
      fermentation and process control.
AB  - For expression of human genes in mammalian cell culture regulatory sequences such
      as promotor or terminator region of viral origin are required. The most widely
      used expression system uses dihydrofolic acid reductase (DHFR) as a selection
      marker in conjunction with a DHFR deficient Chinese hamster ovary (CHO) cell
      using methotrexate as selection pressure. Alternatively the glutamine synthetase
      amplification system seems to be one of the most efficient expression systems
      using methionine sulphoximine (MSX) as selection pressure. Folding and
      glycosylation takes place in mammalian cell cultures at the sites of
      endoplasmatic reticulum and the Golgi apparatus and is comparable to synthesis in
      human cells. Most large scale manufacturing processes for products derived from
      mammalian cell cultures are fed batch suspension culture processes up to 15,000
      l. Important factors for productivity are media composition and feeding
      strategies. Sterility of the entire system during the fermentation period is a
      decisive factor for success rate. Because mammalian cell cultures reacting very
      sensitive to small changes in temperature, pH, osmolality and agitation the
      fermentation system requires a reliable process control system. Validation of the
      entire manufacturing process is required to ensure consistent product quality
      which meets predetermined specifications and to provide a basis for an economic
      process. In a joint effort equipment qualification, process validation, in
      process controls and quality controls provide the basis for product consistency
      from batch to batch.

PMID- 8292074
TI  - Recipe for tragedy: personnel shortages in the public schools.

PMID- 8292073
TI  - Identification of Legionella pneumophila in various specimens by the polymerase
      chain reaction.
AB  - Amplification of the mip sequence with polymerase chain reaction (PCR) proved to
      be specific for Legionella pneumophila. With nested PCR, the sensitivity of the
      test was markedly increased. The lower limit of detection for nested PCR in the
      aqueous medium for live and heat-inactivated dead L. pneumophilia was
      approximately 1-10 bacteria/ml. The sensitivity of the method, however, was
      reduced by a factor of 10 to 100 when the bacteria were added to homogenised
      pulmonary tissue. Fixing the bacteria in aqueous suspension or in tissue
      homogenate with buffered 4% formalin (pH 7.3) reduced the sensitivity of the PCR
      by a factor of about 100. After intravenous injection of heat-inactivated
      bacteria in mice L. pneumophila was detected in deep-frozen samples of plasma and
      various tissues. The molecular biological technique of nested PCR is proposed as
      an additional method for the diagnosis of legionella.

PMID- 8292075
TI  - Disability prevention. Are we ready for the challenge?

PMID- 8292076
TI  - Family-centered approach to promoting communication wellness.

PMID- 8292077
TI  - Is audiology in phase?

PMID- 8292079
TI  - Research and animal welfare.

PMID- 8292078
TI  - Industrial hearing conservation.

PMID- 8292080
TI  - Research and animal welfare.

PMID- 8292081
TI  - Stuttering: what is best practice?

PMID- 8292082
TI  - Multicultural perspectives. Are the issues and questions different?

PMID- 8292083
TI  - In stuttering: do we have an ounce to give?

PMID- 8292084
TI  - Articulation disorders.

PMID- 8292085
TI  - Dysphonia or voice disorders.

PMID- 8292086
TI  - Swallowing disorders.

PMID- 8292087
TI  - Spasmodic dysphonia.

PMID- 8292088
TI  - Barotrauma.

PMID- 8292089
TI  - The effects of n-3 fatty acids on plasma lipids and lipoproteins and other
      cardiovascular risk factors in patients with hyperlipidemia.
AB  - This review discusses the effects of dietary n-3 fatty acids on the plasma
      concentrations and metabolism of lipoproteins with a particular focus on work in
      human subjects. The influence of dietary n-3 fatty acids on the concentrations of
      plasma lipoproteins are affected by the amount of n-3 fatty acids as well as by
      the lipoprotein phenotype in the patients under investigation. On the basis of
      the observed changes in lipoproteins, dietary n-3 fatty acids exert the greatest
      effects on the concentrations of triglyceride-rich lipoproteins; their
      therapeutic potential is greatest in patients with hypertriglyceridemia. In
      addition to their effects on plasma lipoproteins, dietary n-3 fatty acids have
      been reported to exert potentially favorable effects on blood pressure, platelet
      function and viscosity. These effects may justify the use of supplements of
      dietary n-3 fatty acids in selected patients with hypertriglyceridemia to reduce
      the risk of atherosclerosis; however, the benefits of such therapy remain to be
      demonstrated.

PMID- 8292090
TI  - Lipid-related hemostatic abnormalities in the elderly: imbalance between
      coagulation and fibrinolysis.
AB  - To clarify age-related and lipid-related hemostatic abnormalities in the elderly,
      we measured the plasma levels of active PAI-1 antigen (aPAI-1), tPA-PAI-1 complex
      (TPC), plasminogen, alpha 2-plasmin inhibitor (alpha 2-PI), plasmin-alpha 2-PI
      complex (PIC), and D-dimer, together with the plasma levels of fibrinogen, factor
      VII (F VII), and thrombin-antithrombin III complex (TAT) and the serum lipid
      levels in 68 hyperlipidemic and 82 normolipidemic elderly subjects. The aPAI-1
      ratio was calculated as aPAI-1/(aPAI-1 + TPC). In the normolipidemic elderly
      subjects, plasma PIC and D-dimer levels were much higher when compared with
      healthy young controls, and there was also a decrease in plasma plasminogen and
      alpha 2-PI levels, an increase in plasma TPC levels, and high plasma F VII and
      fibrinogen levels. In elderly subjects with type IIb hyperlipidemia, both the
      plasma aPAI-1 level and the aPAI-1 ratio were significantly increased, while the
      plasma PIC and D-dimer levels were reduced despite higher plasma F VII,
      fibrinogen and TAT levels. Both serum total cholesterol and triglyceride levels
      were correlated positively with plasma F VII and TAT levels and with the TAT/PIC
      ratio, while only serum triglyceride levels showed a positive correlation with
      plasma TPC and aPAI-1 levels and with the aPAI-1 ratio. Thus, an increase of
      fibrinolytic activity appears to occur as part of normal aging to balance the
      increase of procoagulant activity. However, an imbalance between thrombin
      activity (increased procoagulant activity) and plasmin activity
      (hypofibrinolysis) appears to occur in elderly individuals with hyperlipidemia,
      perhaps resulting in a predisposition to thromboembolic disease.

PMID- 8292091
TI  - Postprandial changes in apolipoprotein(a) concentration of triglyceride-rich
      lipoproteins can be reproduced by in vitro incubation: implications for
      underlying mechanism.
AB  - We investigated the reciprocal changes in apolipoprotein(a) concentration in the
      lipoprotein of d > 1.006 and the triglyceride-rich lipoprotein (TRL) fractions of
      plasma which occur in vivo following fat ingestion. Twenty fasting subjects were
      studied before and 4 h after a fat-rich meal. In 75% of cases, in vitro
      incubation of the postprandial (4-h) TRL with autologous fasting (0-h)
      lipoproteins of d > 1.006 resulted in further substantial (> 5% total) reciprocal
      changes in apo(a) concentration of the 2 fractions. The increase in re-isolated
      postprandial TRL apo(a) was 25.1% +/- 5.1% of the total apo(a), compared to the
      insignificant increase (0.1% +/- 0.1%) in re-isolated fasting TRL. Most of the
      further increase in 4-h TRL apo(a) (94% +/- 4%) could be achieved by incubation
      with the corresponding 4-h chylomicron fraction (CM) alone. The re-isolated 4-h
      TRL apo(a) concentration correlated positively with 4-h plasma TG concentration
      (r = 0.65, P < 0.01) and other indices of postprandial lipaemia. In vitro
      incubation of pooled serum lipoproteins of d > 1.006 with serial dilutions of
      nascent CM obtained from chylous ascitic fluid revealed that the reciprocal
      changes in apo(a) concentration exhibit a curvilinear relationship with the
      concentration of CM triglyceride which plateaued round 7 mmol/l in this instance.
      We conclude that the reciprocal changes in apo(a) concentration between TRL and
      lipoproteins of d > 1.006 which occur in the postprandial phase are
      quantitatively significant and largely represent a redistribution process rather
      than de novo synthesis because they can be reproduced by in vitro incubation.

PMID- 8292092
TI  - Plasma homocysteine concentrations in Japanese patients with non-insulin
      dependent diabetes mellitus: effect of parenteral methylcobalamin treatment.
AB  - It has been postulated that the accumulation of homocysteine in plasma may induce
      arteriosclerosis. In order to explore the possible contribution of homocysteine
      to the occurrence of macroangiopathy in patients with non-insulin-dependent
      diabetes mellitus, the concentrations of total homocysteine in plasma were
      determined in 52 diabetic patients with clinical macroangiopathy, 84 diabetic
      patients without macroangiopathy, and 57 non-diabetic control subjects. The
      levels of total homocysteine in plasma were significantly higher in diabetic
      patients with macroangiopathy (10.8 +/- 3.8 nmol/ml) than in those without
      macroangiopathy (8.3 +/- 3.1 mmol/ml, P < 0.001) or non-diabetic subjects (7.5 +/
      2.1 nmol/ml, P < 0.001). Among all diabetic patients, multiple logistic
      regression analysis after adjustment for age, sex, and systolic blood pressure
      revealed that high levels of plasma homocysteine were significantly associated
      with the presence of diabetic macroangiopathy (P = 0.01). By an intramuscular
      injection of 1000 micrograms methylcobalamin daily for 3 weeks, the plasma levels
      of homocysteine in 10 diabetic patients were significantly decreased (14.7 +/-
      7.5 vs. 10.2 +/- 6.0 nmol/ml, P < 0.01). Our results suggest that plasma
      homocysteine levels could be one of a number of independent risk factors for
      macroangiopathy in patients with diabetes mellitus and that they can be reduced
      by parenteral treatment with methylcobalamin.

PMID- 8292093
TI  - Cholesterol-lowering drug therapy in a patient with receptor-negative homozygous
      familial hypercholesterolaemia.
AB  - Familial hypercholesterolaemia (FH) is caused by mutations in the gene for the
      low density lipoprotein (LDL) receptor. It is generally believed that homozygous
      FH patients do not respond well to lipid-lowering drug therapy with inhibitors of
      3-hydroxy-3-methylglutaryl CoA reductase because they cannot respond to an
      increased demand for hepatic cholesterol by up-regulation of LDL-receptor
      activity. In this paper we show that serum cholesterol in a homozygous FH patient
      with a receptor-negative LDL-receptor phenotype was reduced by 30% after
      treatment with simvastatin alone and by a further 11% with simvastatin in
      combination with probucol and nicotinic acid. The patient was a true homozygote,
      with two identical alleles of the LDL receptor gene in which a previously
      undescribed point mutation in exon 11 introduces a premature termination codon at
      residue 540 in the protein; the mutant protein is predicted to be truncated in
      the domain with homology to the epidermal growth factor precursor. Cultured cells
      from the patient were unable to bind, internalise or degrade LDL by the receptor
      pathway and there was no immunodetectable LDL receptor protein in the cells. Thus
      the lipid lowering effect of simvastatin in this individual must involve
      mechanisms other than stimulation of LDL receptors.

PMID- 8292094
TI  - Biochemical analysis and mapping of atherosclerotic human artery using FT-IR
      microspectroscopy.
AB  - We report the application of FT-IR microspectroscopy for in situ spectroscopic
      characterization of molecular constituents of human atherosclerotic lesions.
      Since water content in tissue affects conformation-sensitive protein vibrational
      bands, tissue specimens were examined under moist conditions. In all
      measurements, vibrational bands from water were found to dominate the spectrum.
      By removing these water contributions, well resolved bands due to tissue
      components were readily observed. Utilizing the high sensitivity and good spatial
      resolution of IR microspectroscopy, spectra from a sample volume of 40 x 40 x 4
      microns3 were collected using unstained cryostat sections mounted on a BaF2 flat
      in neutral isotonic saline. Microstructures were confirmed histologically by
      light microscopy in stained serial sections. In the spectrum of normal intima,
      major bands due to amide I (1656 cm-1), amide II (1556 cm-1), and CH bending
      (1457 cm-1) vibrations of the proteins collagen and elastin were observed. In the
      spectrum of the intima of noncalcified atherosclerotic plaque, major bands due to
      both proteins and lipids were observed. The lipid bands at 1734, 1468, 1171 and
      1058 cm-1 were assigned to the C = O (ester) stretch, CH2 bend, C--O (ester)
      stretch and C--O stretch, respectively. At a more detailed level, bands specific
      to free cholesterol, and cholesterol esters were identified. A plot of the
      integrated intensity ratio of these bands to the protein amide II mode versus
      depth from the luminal surface confirmed a heterogeneous distribution of these
      constituents in the atheromatous core. In the spectra of calcified
      atherosclerotic plaque, bands were attributed to three types of biochemical
      microstructures: proteins (1657, 1555, 1243 cm-1), lipids (1735, 1466, 1170,
      1085, 1055 cm-1) and calcium minerals such as hydroxyapatite (1094, 1040, 962 cm
      1), and carbonated apatite (1463, 1412, 872 cm-1). The results demonstrate that
      IR microspectroscopy can be used for in situ characterization of molecular
      constituents in human unstained arterial sections. The molecular information
      obtained from these studies could be important in understanding the pathogenesis
      of atherosclerosis.

PMID- 8292095
TI  - Cholesterol levels and prevalence of hypercholesterolemia in Mexican children and
      teenagers.
AB  - In Mexico, the incidence and prevalence of coronary heart disease has increased
      over the past three decades and has become the leading cause of death in some
      areas of the country. Hypercholesterolemia (HC) is a major risk factor for
      coronary atherosclerosis and most developed countries currently have public
      health strategies that attempt to reduce the level of cholesterol. In order to
      learn the mean total cholesterol values and the prevalence of HC, an
      epidemiologic survey was carried out in a representative population sample that
      included men and women aged 1 to 98 years, across the nation. In this report, we
      present the findings in children and teenagers of both sexes (n = 34369).
      Considering the country as a whole, the mean serum TC was 147 +/- 35 mg/dl, the
      prevalence of borderline hypercholesterolemia (TC between 170 and 199 mg/dl) was
      14.7% and the prevalence of high risk hypercholesterolemia (TC > or = 200 mg/dl)
      was 6.7%. This cross sectional study demonstrated the existence of significant
      geographic differences in serum TC, with mean state values ranging from 133 mg/dl
      in the south to 164 mg/dl in the north. The prevalences of high risk
      hypercholesterolemia was as high as 18.2% in Baja California Norte and as low as
      2.5% in the state of Morelos. These geographic differences in total cholesterol
      and prevalence of hypercholesterolemia were already present at one year of age
      and persisted throughout childhood and adolescence.

PMID- 8292096
TI  - Dental infections and coronary atherosclerosis.
AB  - An association between dental and other bacterial infections and coronary heart
      disease has recently been observed in both cross-sectional and longitudinal
      studies. To elucidate this topic, the severity of dental infections and coronary
      atheromatosis was assessed, together with measurements of the conventional
      coronary risk factors, in 100 individuals (88 men, 12 women, mean age 48, range
      28-68 years) referred for diagnostic coronary angiography. Pantomography X-rays
      and coronary angiograms of the participants were scored blindly by single
      observers, a dentist and a radiologist respectively. The median pantomography
      score was 3.0 in male individuals belonging to the highest tertile of coronary
      atheromatosis score, as compared with 0.0 among the rest of the male participants
      (P = 0.003). The association between dental infections and severe coronary
      atheromatosis in males remained significant after adjusting for the effect of
      age, blood lipids, body mass index, hypertension, smoking and social class. No
      association between dental infections and coronary atheromatosis was observed in
      the small number of females studied. This observation supports the proposal that
      bacterial infections play a role in the pathogenesis of coronary atherosclerosis.

PMID- 8292097
TI  - The effect of cholesterol reduction on the endothelial function and progression
      of atherosclerosis in WHHL rabbits.
AB  - In 3-month-old homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits the
      effect of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitor pravastatin was studied for 9 months and related to the
      endothelial function of the coronary arteries of isolated hearts and rings of the
      distal abdominal aorta. Oral administration of pravastatin in doses up to 40
      mg/kg per day significantly decreased plasma cholesterol by 51% in comparison to
      untreated WHHL rabbits. Basal coronary flow and bradykinin-induced increase in
      coronary flow in Langendorff hearts of the pravastatin-treated animals were
      significantly greater than the flow in the control animals, whereas the
      metacholine-induced relaxation of abdominal aortic rings was not different and
      attenuated in comparison to New Zealand white rabbits. The incidence of
      atherosclerotic lesions in four main coronary arteries and the aorta was
      significantly lower in the pravastatin treated animals (25.0% and 52.8%
      respectively) than in untreated WHHL rabbits (34.1% and 80.0% respectively). The
      mean percentage of narrowing in the aorta was also significantly lower in the
      pravastatin-treated group (12.0%) than in the controls (25.2%). Significant
      correlations were found between the extent of atherosclerotic lesions and the
      bradykinin-induced increase in coronary flow versus plasma total cholesterol
      levels. Thus, in this model, long term cholesterol lowering treatment with
      pravastatin starting at an early age retards the progression of plaque formation
      and preserves the endothelium-dependent relaxation of the coronary arteries.

PMID- 8292098
TI  - Metabolism of apolipoprotein B-100 and of triglyceride-rich lipoprotein particles
      in the absence of functional lipoprotein lipase.
AB  - Cholesterol and triglyceride in the various lipoprotein fractions were determined
      in five patients without functional lipoprotein lipase (LPL) while on their
      habitual therapeutic diet of 'low fat' content (20-25 g/day). They were also
      studied following 3 days on either a 'minimal fat' diet (< 15 g/day) or a
      'moderate fat' diet (45-50 g/day). Values obtained were compared with the
      respective levels measured in five control subjects on a 'normal fat' (70-90
      g/day) diet. The patients had hypertriglyceridaemia (type V
      hyperlipoproteinaemia) under all dietary conditions. Cholesterol and triglyceride
      levels in plasma and in the chylomicron fraction increased in the patients with
      increasing dietary fat. In the very low density lipoprotein (VLDL) fraction from
      the patients, triglyceride levels also increased with the dietary fat intake, but
      cholesterol levels were similar under all dietary conditions. In the patients,
      cholesterol concentrations in the low (LDL) and high density (HDL) lipoprotein
      fractions were significantly lower than the respective levels in controls, but
      the ratio of cholesterol to triglyceride levels in both of these lipoprotein
      fractions decreased with the dietary fat intake. VLDL apolipoprotein B-100 (apo B
      100) pool size was similar in the patients on the two test diets (P = 0.95) and
      3.5-fold higher than in five healthy volunteers on a normal fat diet. Using a
      stable isotope enrichment method, the kinetics of apo B-100 were investigated in
      the patients under the last two dietary conditions. The fractional and absolute
      secretion rates of the apolipoprotein in the patients did not vary with fat
      intake, but fractional secretion rates were significantly lower and the absolute
      secretion rates were significantly higher in the patients than the respective
      values in the controls. These results are consistent with the hypothesis that in
      the absence of LPL activity the metabolism of chylomicron and VLDL particles in
      the circulation results in triglyceride-rich LDL and HDL particles that are taken
      up by the liver at increased rates, thus reducing the plasma LDL and HDL
      cholesterol concentrations, whereas the products of hydrolysis of these particles
      induce an increased rate of synthesis of triglyceride and an increased rate of
      secretion of VLDL apo B-100.

PMID- 8292099
TI  - The effects of hypercholesterolaemia, simvastatin and dietary fat on the low
      density lipoprotein receptor of unstimulated mononuclear cells.
AB  - The in vivo expression and regulation of the LDL receptor of circulating
      mononuclear cells was studied using a sensitive spectrophotometric assay with low
      density lipoproteins conjugated to colloidal gold (LDL-gold). The high plasma
      cholesterol of familial hypercholesterolemic subjects was shown to be related to
      a low in vivo LDL receptor activity; cells from a homozygote had virtually no
      activity and those from 24 heterozygotes expressed 45% of the activity of cells
      from 35 normals. The average receptor activity of cells from 18 polygenic
      hypercholesterolemic (PH) subjects was not significantly different from normal
      but a low expression may have been a factor in six of these subjects. Simvastatin
      increased the LDL receptor activity of cells from the PH subjects by 70% while
      lowering their plasma cholesterol by 26%, but reducing the fat intake from 38% to
      20% of energy and cholesterol from 239 to 96 mg/day had no effect on the receptor
      despite a 10% reduction in plasma cholesterol. Upregulation of the LDL receptor
      may therefore have been involved in the lowering of plasma cholesterol by
      simvastatin but not by the reduction in dietary fat and cholesterol.

PMID- 8292100
TI  - Effects of doxazosin, an alpha 1-adrenergic inhibitor, on plasma lipid and
      lipoprotein levels, low density lipoprotein metabolism and cholesterol absorption
      in cynomolgus monkeys.
AB  - The mechanism(s) by which doxazosin, an alpha 1 inhibitor, regulates plasma low
      density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) levels were
      investigated in 'normocholesterolemic' (average total cholesterol (TC) of 218
      mg/dl) and 'hypercholesterolemic' (average TC of 350 mg/dl) cynomolgus monkeys.
      Twelve weeks of doxazosin treatment (1 mg/kg per day) significantly reduced
      plasma TC and LDL-C levels in both groups while high density lipoprotein
      cholesterol and apolipoprotein A-I concentrations rose. Despite these changes in
      plasma lipids, LDL and HDL lipid composition was not affected by doxazosin. The
      reduction in LDL-C and apo B in the doxazosin-treated 'hypercholesterolemic'
      group was associated with a significant increase in both receptor-dependent and 
      independent LDL apo B fractional catabolic rates. Similar associations were noted
      in the 'normocholesterolemic' group. LDL apo B production or transport rate was
      not affected by doxazosin. Cholesterol absorption was also significantly reduced
      by doxazosin which may also contribute to lowering plasma LDL-C levels. These
      studies suggest that doxazosin treatment can produce beneficial changes in the
      plasma lipid profile over a wide rage of plasma cholesterol levels by up
      regulating LDL fractional clearance.

PMID- 8292101
TI  - Evidence for soluble and nuclear site I binding of estrogens in human aorta.
AB  - The purpose of this study was to establish the estrogen receptor (ER) expression
      and content in human aorta fragments removed at the time of by-pass surgery. To
      this end, we adopted a radioligand binding assay to evaluate either soluble (S)
      or nuclear (N) ER using dextran-coated charcoal (DCC) and filtration methods,
      respectively. To better define the intratissular distribution and content of ER,
      we also measured the presence of a 27 kDa heat shock protein (HSP27), a well
      established ER-associated protein, using D5 monoclonal antibody. Finally, we
      analysed the different molecular isoforms of both S and N ER using size exclusion
      high performance liquid chromatography (SE-HPLC). High affinity (type I) sites of
      estrogen binding were detected in 17 out of 19 samples in either S or N fraction,
      although only 9 out of 19 cases displayed site 1 ER in both cell compartments. ER
      levels in aortic tissues, detected by radioligand method, compare well with those
      we have found in other hormone-sensitive human cancer tissues and cells. SE-HPLC
      analysis revealed two main receptor isoforms in the soluble fraction, having 65
      kDa and 18 kDa molecular mass, while a minor component of 29 kDa was also found;
      the nuclear fraction displayed again two major components of 38 and 23 kDa. Using
      the HSP27 immunohistochemistry we observed a major staining occurring in smooth
      muscle cells (SMC), with an increasing intensity towards the lumen. All samples,
      including the ER negative ones, exhibited some degree of histochemical staining.
      Using an arbitrary cut-off value, 7 out of 12 samples displayed a highly positive
      staining, 6 of which showed nuclear ER. Furthermore, SE-HPLC separation indicated
      the presence of a 64.9 kDa component in the soluble fraction, according to the
      well known relative molecular mass of ER. Following HSP27 immunohistochemistry,
      the overall staining intensity in aortic SMC approaches that seen in endometrial
      and breast epithelia, whilst the muscle ER content is generally lower. Although
      our data are compatible with a direct role of estrogens in arterial function, the
      extent of the link with arterial disease remains to be established.

PMID- 8292102
TI  - Proteoglycans and endothelial barrier function: effect of linoleic acid exposure
      to porcine pulmonary artery endothelial cells.
AB  - Certain fatty acids induce changes in endothelial barrier function which may be
      mediated by alterations in normal proteoglycan synthesis/metabolism. To test this
      hypothesis, pulmonary artery derived endothelial cells were treated with media
      supplemented with linoleic acid (18:2), and/or a known proteoglycan synthesis
      inhibitor, beta-D-xyloside. Independent exposure to 1 mM beta-D-xyloside or 90
      microM 18:2 increased albumin transfer, i.e., decreased barrier function, when
      compared with control cultures. 18:2 and beta-D-xyloside increased albumin
      transfer additively, suggesting that the mechanisms by which 18:2 and beta-D
      xyloside alter the proteoglycan metabolism are different. Compared with the
      control group, treatment with 18:2 inhibited proteoglycan synthesis, decreased
      anionic properties of heparan sulfate proteoglycans in the cell monolayers and
      caused the release of a unique chondroitin sulfate proteoglycan into the culture
      media. Treatment with beta-D-xyloside caused an increased incorporation of
      radioactive sulfate into glycosaminoglycans but inhibited proteoglycan synthesis.
      These results suggest that the fatty acid- and beta-D-xyloside-induced impairment
      in endothelial barrier function may involve changes in the synthesis, release and
      physicochemical properties of proteoglycans.

PMID- 8292103
TI  - Effect of an atherogenic diet on lipoprotein cholesterol profile in the F1B
      hybrid hamster.

PMID- 8292104
TI  - Meningococcal disease in a pediatric population in San Diego County.

PMID- 8292105
TI  - Compendium of physical activities: classification of energy costs of human
      physical activities.
AB  - A coding scheme is presented for classifying physical activity by rate of energy
      expenditure, i.e., by intensity. Energy cost was established by a review of
      published and unpublished data. This coding scheme employs five digits that
      classify activity by purpose (i.e., sports, occupation, self-care), the specific
      type of activity, and its intensity as the ratio of work metabolic rate to
      resting metabolic rate (METs). Energy expenditure in kilocalories or kilocalories
      per kilogram body weight can be estimated for all activities, specific
      activities, or activity types. General use of this coding system would enhance
      the comparability of results across studies using self reports of physical
      activity.

PMID- 8292106
TI  - Autosomal dominant inheritance of iridogoniodysgenesis and cataract.
AB  - BACKGROUND: There has been only one report in the literature of
      iridogoniodysgenesis associated with cataracts in two brothers. In that report,
      the authors conclude that the condition was inherited by autosomal recessive
      transmission. METHODS: The authors evaluated 10 members in three generations of a
      family in which there is a striking prevalence of pre-senile hypermature cataract
      formation and iridogoniodysgenesis. In addition, historical information regarding
      two deceased members of the family was studied. RESULTS: Six of 10 family members
      evaluated have iridogoniodysgenesis. Four of five siblings have had pre-senile
      hypermature cataracts. Despite the iridogoniodysgenesis, there appears to be no
      association with glaucoma in any of these patients. CONCLUSION: The inheritance
      pattern of this syndrome appears to be that of autosomal dominance with variable
      penetrance. The authors believe that this report helps to clarify the inheritance
      pattern of this previously described hereditary syndrome.

PMID- 8292107
TI  - Hepatotoxicity associated with angiotensin-converting enzyme inhibitors.
AB  - OBJECTIVE: To review published reports of hepatotoxicity associated with
      angiotensin-converting enzyme (ACE) inhibitors and to explore possible mechanisms
      of injury. DATA SOURCES: Published reports of hepatotoxicity associated with use
      of ACE inhibitors and investigations that suggest potential mechanisms of injury.
      DATA SYNTHESIS: Nineteen cases of ACE-inhibitor-associated hepatotoxicity are
      presented. Early theories regarding mechanisms are reviewed. Laboratory
      investigations of hepatic effects of eicosanoids on hepatic function are reviewed
      and a novel mechanism by which ACE inhibitors may cause hepatic injury is
      postulated. CONCLUSIONS: Hepatotoxicity, usually cholestatic in nature, has been
      reported with captopril, enalapril, and lisinopril use. Apparent cross-reactivity
      has been reported twice. Potential mechanisms of injury include idiopathic
      hypersensitivity and modulation of eicosanoid metabolism by inhibition of
      kininase II and subsequent increased hepatic bradykinin activity. Mediation via
      altered eicosanoid metabolism provides a plausible explanation for cross
      reactivity among ACE inhibitors. Hepatotoxicity resolves if ACE inhibitors are
      stopped but may progress to liver failure if treatment is continued.

PMID- 8292108
TI  - Doctors, death and Sue Rodriguez.

PMID- 8292109
TI  - Chlamydia pneumoniae infections.

PMID- 8292110
TI  - A new technique for combined spinal and epidural anesthesia.

PMID- 8292111
TI  - Sensitivity and specificity of potassium hydroxide smears of skin scrapings for
      the diagnosis of tinea pedis.

PMID- 8292112
TI  - Fully implantable venous access systems.

PMID- 8292113
TI  - Blood transfusions and prognosis in colorectal cancer.
AB  - BACKGROUND: Blood transfusions may adversely affect the prognosis of patients
      treated surgically for cancer, although definite proof of this adverse effect has
      not been reported. METHODS: We carried out a randomized trial to investigate
      whether the prognosis in patients with colorectal cancer would be improved by a
      program of autologous blood transfusion as compared with the current practice of
      allogeneic transfusion. Patients in the autologous-transfusion group were
      required to donate two units of blood before surgery. RESULTS: A total of 475
      patients were evaluated. We found no significant difference in prognosis between
      the allogeneic-transfusion group (236 patients) and the autologous-transfusion
      group (239 patients); colorectal cancer-specific survival rates at four years
      were 67 percent and 62 percent, respectively (P = 0.39). Among the 423 patients
      who underwent curative surgery, 66 percent of those in the allogeneic-transfusion
      group and 63 percent of those in the autologous-transfusion group had no
      recurrence of colorectal cancer at four years (P = 0.93). We also found that the
      risk of recurrence was significantly increased in patients who received blood
      transfusions, either allogeneic or autologous, as compared with patients who did
      not require transfusions; the relative rates of recurrence were 2.1 (P = 0.01)
      and 1.8 (P = 0.04), respectively; these rates did not differ significantly from
      each other. CONCLUSIONS: The use of autologous blood as compared with allogeneic
      blood for transfusion does not improve the prognosis in patients with colorectal
      cancer. Regardless of their type, transfusions are associated with poor
      prognosis, probably because of the circumstances that necessitate them.

PMID- 8292114
TI  - Visceral infection caused by Leishmania tropica in veterans of Operation Desert
      Storm.
AB  - BACKGROUND: Visceral leishmaniasis, usually caused by Leishmania donovani, has
      rarely been reported from eastern Saudi Arabia, so it was not expected to affect
      the soldiers of Operation Desert Storm. METHODS: We evaluated eight soldiers with
      visceral leishmanial infection, examining their serum with an immunofluorescent
      antibody assay, examining their marrow or biopsy tissue for amastigotes with an
      indirect immunofluorescent-monoclonal-antibody assay, and culturing the
      parasites. Cultured promastigotes were isolated and characterized by isoenzyme
      analysis. RESULTS: None of the eight soldiers had classic signs or symptoms of
      visceral leishmaniasis (kala-azar). Seven soldiers had unexplained fever, chronic
      fatigue, malaise, cough, intermittent diarrhea, or abdominal pain that began up
      to seven months after they returned to the United States; one had no symptoms.
      Five had adenopathy or mild, transient hepatosplenomegaly. None had cutaneous
      manifestations. Diagnoses were made by bone marrow aspiration (seven patients) or
      lymph-node biopsy (one patient). Six isolates have been identified as L. tropica,
      which usually causes only cutaneous disease. Of the six patients treated with
      sodium stibogluconate, five improved and one remained symptomatic. CONCLUSIONS:
      L. tropica can produce visceral infection that can cause unexplained systemic
      illness in persons returning from areas where this organism is endemic.

PMID- 8292115
TI  - Use of benzodiazepines in anxiety disorders.

PMID- 8292116
TI  - Screening for renovascular hypertension.

PMID- 8292117
TI  - The essential psychotherapies.

PMID- 8292118
TI  - Reducing bacteria in dental aerosols: pre-procedural use of an antiseptic
      mouthrinse.
AB  - This study, using a simulated office visit model, showed that the pre-procedural
      use of an antimicrobial mouthrinse produces a significant reduction in number of
      viable bacteria in a dental aerosol.

PMID- 8292119
TI  - Lumpectomy compared with lumpectomy and radiation therapy for the treatment of
      intraductal breast cancer.
AB  - BACKGROUND AND METHODS: Women with ductal carcinoma in situ have been treated
      both by lumpectomy and by lumpectomy followed by radiation therapy, but the
      benefit of combined therapy is uncertain. A group of 818 women with ductal
      carcinoma in situ were randomly assigned to undergo lumpectomy or lumpectomy
      followed by breast irradiation (50 Gy). Sufficient tissue was removed that the
      margins of the resected specimens were histologically tumor-free. The mean
      duration of follow-up was 43 months (range, 11 to 86). The principal end point of
      the study was event-free survival, as defined by the presence of no new
      ipsilateral or contralateral breast cancers, regional or distant metastases, or
      other cancers and by no deaths from causes other than cancer. RESULTS: Five-year
      event-free survival was better in the women who received breast irradiation (84.4
      percent, vs. 73.8 percent for the women treated by lumpectomy alone; P = 0.001).
      The improvement was due to a reduction in the occurrence of second ipsilateral
      breast cancers; the incidence of each of the other events was similar in the two
      groups. Of 391 women treated by lumpectomy alone, ipsilateral breast cancer
      developed in 64 (16.4 percent); it was noninvasive in 32 and invasive in the
      remaining 32. Of 399 women treated with lumpectomy and breast irradiation,
      ipsilateral breast cancer developed in 28 (7.0 percent) (noninvasive in 20 and
      invasive in 8). The five-year cumulative incidence of second cancers in the
      ipsilateral breast was reduced by irradiation from 10.4 percent to 7.5 percent
      for noninvasive cancers and from 10.5 percent to 2.9 percent for invasive cancers
      (P = 0.055 and P < 0.001, respectively). CONCLUSIONS: Breast irradiation after
      lumpectomy is more appropriate than lumpectomy alone for women with localized
      ductal carcinoma in situ.

PMID- 8292120
TI  - Standardization of IVGTT. Importance of method used to calculate glucose
      disappearance.

PMID- 8292121
TI  - Participation of HIV-infected patients in autologous blood programs.

PMID- 8292122
TI  - Intestinal malrotation in infants.

PMID- 8292123
TI  - Sudden death in young athletes. Lessons from the Hank Gathers affair.

PMID- 8292124
TI  - Management of the posterior capsule during pediatric intraocular lens
      implantation.
AB  - One of the major obstacles in pediatric intraocular lens implantation has been
      the subsequent dense opacification of the posterior capsule. We used a
      modification of the standard pediatric cataract surgical procedure, which
      involved endocapsular cataract extraction, posterior chamber intraocular lens
      implantation, pars plana posterior capsulotomy, and pars plana anterior
      vitrectomy in 20 consecutive patients with unilateral traumatic, radiation
      induced, and developmental cataracts. Visual axes were rapidly restored in all
      patients without further intervention for posterior capsule opacification. Visual
      acuity returned to 20/40 or better in all patients and 75% of all patients (15
      patients) reached maximum improvement by five weeks. No complications attributed
      to intraoperative removal of the posterior capsule occurred.

PMID- 8292125
TI  - A family perspective on supported housing.

PMID- 8292126
TI  - Complications of the skin level gastrostomy device.

PMID- 8292127
TI  - Tips for starting your own nurse practitioner practice.
AB  - The decision to open a nurse practitioner practice is often difficult to make.
      Success depends on the possession of specific resources, such as adequate skills,
      finances, emotional support and the desire to be one's own boss. These skills
      will be critical as the NP develops a business plan and a budget, and makes
      important decisions, such as the form the business will take: sole
      proprietorship, partnership or corporation. Using external resources such as
      attorneys and accountants is also useful, especially when tackling issues of
      licenses, taxes and insurance. Start-up costs can be kept to a minimum with
      creativity and used equipment. In-house laboratories and reference laboratories
      must conform to strict regulations. A practice without established patients will
      need to market services aggressively through a successful mix of product, price,
      place and promotion. Patients' acceptance of the NP office will be enhanced by
      smooth patient flow, adequate space and cleanliness.

PMID- 8292128
TI  - Triazolam. Unpublished manufacturers research unfavourable.

PMID- 8292129
TI  - A prospective study of the intake of vitamins C, E, and A and the risk of breast
      cancer.
AB  - BACKGROUND: Although it has been hypothesized that large intakes of the
      antioxidant vitamins C, E, and A reduce the risk of breast cancer, few
      prospective data are available. METHODS: We prospectively studied 89,494 women
      who were 34 to 59 years old in 1980 and who did not have cancer. Their intakes of
      vitamins C, E, and A from foods and supplements were assessed at base line and in
      1984 with the use of a validated semiquantitative food-frequency questionnaire.
      RESULTS: Breast cancer was diagnosed in 1439 women during eight years of follow
      up. After multivariate adjustment for known risk factors, the relative risk among
      women in the highest quintile group for intake of vitamin C as compared with the
      risk among those in the lowest quintile group was 1.03 (95 percent confidence
      interval, 0.87 to 1.21); for vitamin E, after vitamin A intake had been
      controlled for, the relative risk was 0.99 (95 percent confidence interval, 0.83
      to 1.19). In contrast, among women in the highest quintile group for intake of
      total vitamin A the relative risk was 0.84 (95 percent confidence interval, 0.71
      to 0.98; P for trend = 0.001). Among women in the lowest quintile group for
      intake of vitamin A from food, consumption of vitamin A from supplements was
      associated with a reduced risk (P = 0.03). The significant inverse association of
      vitamin A intake with the risk of breast cancer was also found on study of data
      based on the 1984 questionnaire and four years of follow-up. CONCLUSIONS: Large
      intakes of vitamin C or E did not protect women in our study from breast cancer.
      A low intake of vitamin A may increase the risk of this disease; any benefit of
      vitamin A supplements may be limited to women with diets low in vitamin A.

PMID- 8292130
TI  - The role of melatonin and serotonin in aging: update.
AB  - It has been proposed that aging occurs because of a failure of the pineal gland
      to produce melatonin from serotonin each day beginning at sunset and throughout
      the night. This lack leads to a nighttime deficiency of melatonin both absolutely
      and also relatively to serotonin. As melatonin has wide-spread integrative and
      regenerative effects, its lack may lead to disturbances normally associated with
      aging. The present paper reviews the pertinent literature which appeared since
      our first publication, but earlier articles are also included. Evidence is
      presented for a role of melatonin and serotonin in controlling the neuroendocrine
      and immune networks and in inhibiting the development of ischemic heart and
      Alzheimer's disease, tumor formation and other degenerative processes associated
      with aging. The possible role of melatonin in the favourable effects of dietary
      restriction on aging is also discussed. This paper provides additional evidence
      that a melatonin deficiency, especially in relation to serotonin, may be
      responsible for the promotion of aging in the organism.

PMID- 8292131
TI  - Anaesthesia for the porphyric patient.

PMID- 8292132
TI  - The levering laryngoscope.
AB  - This is a report of a modification of the standard Macintosh laryngoscope blade
      to facilitate tracheal tube placement in cases of difficult visualisation of the
      larynx. The modification offers the unique advantage of a hinged blade tip,
      controlled by a lever on the handle of the laryngoscope which allows elevation of
      the epiglottis while decreasing the overall laryngoscopic elevation or levering
      movement required. It is an adaptation which can be applied to most laryngoscope
      blades, does not require any special training in its use and will prove useful
      for both routine intubations as well as those which may be difficult and
      associated with an anterior larynx.

PMID- 8292133
TI  - Administrative costs in U.S. hospitals.
AB  - BACKGROUND: Previous estimates of administrative costs in U.S. hospitals have
      been based on figures for California, and nationwide extrapolation has been
      controversial. If the costs of bureaucracy are high, major policy reforms may
      yield substantial savings. METHODS: We obtained detailed data on hospital
      expenses for fiscal year 1990 from reports submitted to Medicare by 6400
      hospitals. We calculated each hospital's administrative costs by summing expenses
      in the following Medicare cost-accounting categories: administrative and general,
      nursing administration, central services and supply (excluding the purchase cost
      of supplies), medical records and library, utilization review, and the salary
      costs of the employee benefits department. We classified costs in most other
      categories as clinical. Some small categories of expenses (e.g., gift shop) were
      excluded from both our clinical and administrative groupings, and for others
      (e.g., plant operations), a proportional share was allocated between the two
      groupings. RESULTS: Nationwide, administration accounted for an average of 24.8
      percent of each hospital's spending in fiscal 1990. Average hospital
      administrative costs ranged from 20.5 percent in Minnesota to 30.6 percent in
      Hawaii. Administrative salaries accounted for 22.4 percent of the average
      hospital's salary costs. Administrative costs were similar in states with high
      and low rates of enrollment in health maintenance organizations (HMOs).
      CONCLUSIONS: Hospital administrative costs in the United States are higher than
      previous estimates and more than twice as high as those in Canada. Greater
      enrollment in HMOs, with more competitive bidding by hospitals for managed-care
      contracts, an important element of proposed managed-competition health care
      reforms, does not seem to lower hospital administrative costs.

PMID- 8292135
TI  - Kurtzke scale.

PMID- 8292134
TI  - Occurrence of Andermann syndrome out of French Canada--agenesis of the corpus
      callosum with neuronopathy.
AB  - We report on two siblings, a boy and a girl, with agenesis of corpus callosum and
      neuronopathy. The children show diffuse hypotonia, delayed motor and mental
      development. Neurophysiological examinations revealed reduction of the motor
      nerve conduction velocity, absence of sensory nerve action potentials, abnormal
      somatosensory and visual evoked potentials. Nerve biopsies showed reduced density
      of myelinated and unmyelinated fibres in both children. We also found signs of
      hypomyelination and suggest this is secondary to degeneration of peripheral
      sensory and motor neurons. Our findings are consistent with the diagnosis of
      Andermann syndrome. This is the first report of the occurrence of Andermann
      syndrome out of French Canada.

PMID- 8292136
TI  - Age and gender effects on nasal respiratory function in normal subjects.
AB  - One hundred and ninety-seven normal individuals between the ages of 5 and 73
      years were evaluated to determine nasal resistance, nasal cross-sectional area,
      and respiratory mode during quiet breathing. Subjects were categorized into three
      age groups. Nasal resistance and respiratory mode were directly determined using
      posterior rhinomanometry and the SNORT technique, respectively. Nasal cross
      sectional area was estimated using the hydrokinetic equation. Results indicated
      significant effects of age on all variables; significant gender differences were
      found for respiratory mode. Weak correlations were found between respiratory mode
      and nasal resistance. The results are presented as normative data on
      nasorespiratory characteristics to facilitate diagnostic and treatment decisions
      relative to individuals with normal morphology as well as to patients with
      craniofacial anomalies. A fundamental issue of both clinical and theoretical
      importance arising from the study pertains to the definitions of normality and
      impairment.

PMID- 8292137
TI  - Dispensing in general practice. Legal pitfalls with generic prescribing.

PMID- 8292138
TI  - Cornification of esophagus induced by excessive vitamin E.
AB  - The antagonistic effects of vitamin E on vitamin A were studied in chickens fed
      excessive amounts of vitamin E (700-7000 IU/kg diet) for 6 wk. Serum levels of
      vitamin A and vitamin E were determined by high-performance liquid chromatography
      at 2, 4, and 6 wk after vitamin E supplementation. Vitamin E in serum reached
      maximum levels 4 wk after supplementation. Vitamin E tended to ameliorate the
      normalization of serum levels of vitamin A. To examine the pathological lesions
      induced by excessive vitamin E in chickens, two to four chickens were necropsied
      every 2 wk after supplementation. The results in gross and microscopic lesions
      showed that cornification of esophageal mucous membrane was found in chickens
      supplemented with > or = 1400 IU/kg of vitamin E in diet for 6 wk. Lesions of
      this kind resemble those in vitamin A-deficient chickens and are the first to be
      induced by excess vitamin E.

PMID- 8292139
TI  - Animals and the environment.

PMID- 8292140
TI  - Queensland tick typhus in Sydney Harbour.

PMID- 8292141
TI  - Role of retinoic acid, a derivative of vitamin A (retinol), in tissue development
      and maintenance.

PMID- 8292142
TI  - [Life-terminating actions in severely demented patients].

PMID- 8292143
TI  - Management of pneumothorax. Chest drain trocar unsafe and unnecessary.

PMID- 8292144
TI  - More on the pharmaceutical quagmire.

PMID- 8292145
TI  - Aspirin and myocardial infarction.

PMID- 8292146
TI  - Calorie-restricted weight reduction, blood pressure, and atrial natriuretic
      peptides.

PMID- 8292147
TI  - Zidovudine dosage. Nordic Medical Research Councils' HIV Therapy Group.

PMID- 8292148
TI  - Bronchodilator treatment in asthma.

PMID- 8292149
TI  - Dispensing in general practice.

PMID- 8292150
TI  - Learning from Tracy [corrected].

PMID- 8292151
TI  - Photoplethysmography in the diagnosis of superficial venous valvular
      incompetence.

PMID- 8292152
TI  - Patient recruitment for clinical research.

PMID- 8292153
TI  - Hyperkalaemia after warm heart surgery.

PMID- 8292154
TI  - Diagnosing canine borreliosis.

PMID- 8292155
TI  - Current dermatologic therapy: use of interferons in genital warts.

PMID- 8292156
TI  - The DAB-Mn++ cytochemical method revisited: validation of specificity for
      superoxide.
AB  - We wished to assess whether the previously developed 3,3'-diaminobenzidine (DAB)
      Mn++ cytochemical method, purportedly specific for superoxide localization, is
      detecting superoxide O2.- and/or the superoxide product, O2(1 delta g). We show
      here that polymorphonuclear leukocytes (PMNs) produce O2(1 delta g)
      extracellularly in response to non-phagocytic stimuli and that this production is
      inhibited by addition of superoxide dismutase, an enzyme typically used to
      demonstrate that a reaction is mediated by O2.-. Because O2(1 delta g) is highly
      reactive and can be generated from O2.-, the reactivity of a pure chemical source
      of O2(1 delta g) with the cytochemical probe DAB was examined in the presence and
      absence of Mn++. Reactions between DAB and O2(1 delta g), thermally released from
      1,4-dimethyl-napthalene-1,4-endoperoxide (DNE), indicated that O2(1 delta g)
      directly reacted with DAB, forming an insoluble DAB polymer, and that this
      reaction was increased by the presence of Mn++. The direct reaction of O2(1 delta
      g) with DAB was confirmed using near-IR emission spectroscopy. The near-IR
      emission spectrum of DNE as it was warmed showed the characteristic energy
      emission peak of O2(1 delta g) and the intensity of this peak was reduced by the
      addition of DAB; kq = 1.7 x 10(8) M-1 sec-1. The requirement of Mn++ for
      oxidation of DAB by O2.- was reconfirmed using potassium superoxide as a pure
      chemical source of O2.-. In cell studies, however, DAB deposits were not observed
      in PMNs stimulated under conditions that lead to O2(1 delta g) production [e.g.,
      0.040 or 0.162 microM 4B-phorbol-12-myristate-13-acetate (PMA)], regardless of
      whether Mn++ was present in the cytochemical medium. Nor were DAB deposits found
      in cells stimulated with PMA in the absence of Mn++ or in unstimulated PMNs. Only
      cells incubated in cytochemical medium containing Mn++ and stimulated to produce
      large amounts of O2.- (e.g., 3.24 microM PMA) contained DAB deposits. In summary,
      the DAB-Mn++ cytochemical method remains an excellent method for localizing the
      production sites of O2.-, since the concentration of O2(1 delta g) within
      vesicles of stimulated cells is too low to directly oxidize DAB to an electron
      dense deposit.

PMID- 8292158
TI  - Using MEDLINE to solve clinical problems.

PMID- 8292157
TI  - Simultaneous detection of immunophenotype and genome by the MAC method.

PMID- 8292159
TI  - Absence of seroconversion of HIV-1 antibody in seroreactive individuals.

PMID- 8292160
TI  - Medical management of miscarriage with RU486.

PMID- 8292161
TI  - Computer-assisted learning in medical education in psychiatry.

PMID- 8292162
TI  - Screening for colorectal cancer.

PMID- 8292163
TI  - Screening for colorectal cancer.

PMID- 8292164
TI  - Hormonal contraception.

PMID- 8292165
TI  - Women's decisions about abortion.

PMID- 8292166
TI  - Cutaneous disease and drug reactions in HIV infection.

PMID- 8292167
TI  - Food for New Zealanders.

PMID- 8292168
TI  - Fluoridation and bones.

PMID- 8292169
TI  - Influenza mimicking Kawasaki disease.

PMID- 8292170
TI  - Trends in AIDS epidemic.

PMID- 8292171
TI  - Questions about electrographic seizures in newborns.

PMID- 8292172
TI  - Shunts in patients with respiratory distress syndrome.

PMID- 8292173
TI  - "Getting real" about HIV and homeless youth.

PMID- 8292174
TI  - The effect of two levels of hypotension on intraoperative blood loss during total
      hip arthroplasty performed under epidural anesthesia.

PMID- 8292175
TI  - Quantifying lymphocytes in bronchoalveolar lavage fluid.

PMID- 8292176
TI  - Importance of renal artery stenosis in normotensive patients.

PMID- 8292177
TI  - 'Department of Health guidelines for HCWs with HIV/AIDS infection'.

PMID- 8292178
TI  - Heart transplantation for acute occlusion of the left main coronary artery.

PMID- 8292179
TI  - Recognizing cognitive impairment.

PMID- 8292180
TI  - Drug treatment during Ramadan. Stopping bronchodilator treatment is dangerous.

PMID- 8292181
TI  - Drug abuse related emergency room episodes in United States and in Spain.

PMID- 8292182
TI  - Pathophysiology of nonsteroidal antiinflammatory drug-induced intestinal
      strictures.

PMID- 8292183
TI  - Antiphospholipid antibody syndrome.

PMID- 8292184
TI  - Determination of mitral regurgitant flow rate from color flow maps of the
      regurgitant flow convergence region.

PMID- 8292185
TI  - Effect of aging on body fat.

PMID- 8292186
TI  - Ulnar shortening osteotomy for ulnar impaction syndrome.

PMID- 8292187
TI  - Nosocomial aspergillosis in lymphoma patients.

PMID- 8292188
TI  - Management of neonatal citrullinemia.

PMID- 8292189
TI  - Screening for thyroid dysfunction: which test is best?

PMID- 8292190
TI  - Experimental vein grafts.

PMID- 8292191
TI  - Acute epiglottitis.

PMID- 8292192
TI  - "Rules of life" key to improving adolescent health.

PMID- 8292193
TI  - Administrative costs and health care reform.

PMID- 8292194
TI  - Ovarian management during radical hysterectomy in the premenopausal patient.

PMID- 8292195
TI  - Inherited iridogoniodysgenesis.

PMID- 8292196
TI  - Guam ALS-PDC: possible causes.

PMID- 8292197
TI  - Beta-carotene accumulation in serum and skin.

PMID- 8292198
TI  - Comment on joint unloading.

PMID- 8292199
TI  - Development of thyroid dysfunction after alpha-interferon treatment of chronic
      hepatitis C.

PMID- 8292200
TI  - Re: "The harm reduction approach and risk factors for human immunodeficiency
      virus (HIV) seroconversion in injecting drug users, Amsterdam".

PMID- 8292201
TI  - Stroke mortality trends and antihypertensive drug use.

PMID- 8292202
TI  - A randomized trial of vitamin A and vitamin E supplementation for retinitis
      pigmentosa.

PMID- 8292203
TI  - ABC of emergency radiology. Chest radiographs--I.

PMID- 8292204
TI  - Satisfaction with access to general practitioner services in south Auckland.
AB  - AIMS: To describe satisfaction with access to general practitioner services in
      south Auckland. METHODS: A random population survey of established residents was
      undertaken with the sample drawn from electoral rolls. A questionnaire was
      administered face-to-face by trained interviewers. Satisfaction was graded using
      a five point scale, with standard "smiley faces" as visual cues. RESULTS: Overall
      satisfaction levels are high, ranging from 3.00 to 4.41 out of a maximum of 5.
      The lowest satisfaction is reported with charges (3.00), home visiting (3.31),
      weekend services (3.39), after hours services (3.48), and waiting times (3.55).
      Satisfaction is lowest amongst Polynesians and the 18-29 age group. CONCLUSIONS:
      General practitioners could increase patient satisfaction with access by reducing
      patient charges and waiting times, and by improving access to services not
      provided at their usual premises during normal hours. Further research is needed
      into reasons for low satisfaction in the nonEuropean and younger age groups.

PMID- 8292205
TI  - The sixth Nationwide Tuberculosis Prevalence Survey in Korea, 1990.
AB  - SETTING: Nationwide random sample survey for tuberculosis in 1990. OBJECTIVE: To
      investigate the prevalence of tuberculosis infection, morbidity and drug
      resistance and BCG coverage, and to compare the findings with those of the
      previous 5 surveys. DESIGN: The following investigations were performed:
      tuberculin test, BCG scar screening, chest miniature radiography (70 mm x 70 mm)
      for those aged over 5 years, sputum direct smear, culture and drug susceptibility
      test, and a questionnaire to obtain history of chemotherapy and symptoms.
      RESULTS: The coverage of the investigation has been of more than 95% in each
      survey. The main findings are as follows: BCG coverage of those aged under 30 and
      of infants (aged under 1 year) has increased from 24% to 86% and from 1% to 79%
      respectively. The observed tuberculin positivity (> or = 10 mm in diameter) of
      subjects aged under 30 has decreased from 45% to 27%. The reduction of positivity
      was significant in children aged 5-9 years, from 34% to 8%. The annual risk of
      infection has dropped by over 6% annually. The prevalence of pulmonary
      tuberculosis per 100,000 has decreased: direct smear-positive from 690-143, smear
      and/or culture positive from 940-241 and active cases from 5065-1842
      respectively. The drug resistance rate had increased to the peak of 47% in 1980,
      but had decreased to 27% in the last survey. CONCLUSION: The tuberculosis
      situation has improved significantly in every aspect in the last 25 years.

PMID- 8292206
TI  - Purification and some properties of an alkaline xylanase from alkaliphilic
      Bacillus sp. strain 41M-1.
AB  - An alkaliphilic Bacillus sp. strain, 41M-1, isolated from soil produced multiple
      xylanases extracellularly. One of these xylanases was purified to homogeneity by
      ammonium sulfate fractionation and anion-exchange chromatography. The moleculr
      mass of this enzyme (xylanase J) was 36 kDa, and the isoelectric point was pH
      5.3. Xylanase J was most active at pH 9.0. The optimum temperature for the
      activity at pH 9.0 was around 50 degrees C. The enzyme was stable up to 55
      degrees C at pH 9.0 for 30 min. Xylanase J was completely inhibited by the
      Hg2+ion and N-bromosuccinimide. The predominant products of xylan hydrolysate
      were xylobiose, xylotriose, and higher oligosaccharides, indicating that the
      enzyme was an endoxylanase. The apparent Km and Vmax values on xylan were 3.3
      mg/ml and 1,100 micromol-1 mg-1, respectively. Xylanase J showed high sequence
      homology with the xylanases from Bacillus pumilus and Clostridium acetobutylicum
      in the N-terminal region. Xylanase J acted on neither crystalline cellulose nor
      carboxymethyl cellulose, indicating a possible application of the enzyme in
      biobleaching processes.

PMID- 8292207
TI  - Benign hereditary chorea.
AB  - Benign hereditary chorea is an uncommon inherited form of childhood chorea that
      can be mistaken for much more serious disorders, such as Huntington disease. The
      clinical manifestations of this condition are reviewed, emphasizing the
      differential diagnosis, treatment modalities, and evaluation of childhood chorea.

PMID- 8292208
TI  - Neurogenic arthrogryposis multiplex congenita: clinical and MRI findings.
AB  - A clinical and magnetic resonance imaging (MRI) study on a selected group of 11
      children, with a diagnosis of neurogenic arthrogryposis multiplex congenita (AMC)
      based on clinical, electromyographic, and muscle biopsy findings, is presented to
      determine the extent of central nervous system involvement in AMC. Family
      history, pregnancy, perinatal problems, other abnormalities, and epileptic
      seizures were reviewed. Neurologic examination, electroencephalography,
      intellectual assessment, and MRI study both of spinal cord and brain were
      performed. The clinical and laboratory findings disclosed evidence of spinal cord
      lesions with involvement of anterior horn cell function in all patients, and
      impairment of cerebral function in 5 patients. MRI revealed spinal cord atrophy
      in 3 patients, diffuse atrophy in 2 patients, and involved thoraco-lumbar
      segments in 1 patient. Cranial MRI studies demonstrated features of developmental
      brain abnormalities in 3 patients, cortical frontal atrophy in 2, and was normal
      in 4. In neurogenic AMC patients, MRI examination of the spinal cord and brain
      may help to clarify the pathogenesis of the disease and is helpful for prognostic
      and therapeutic purposes.

PMID- 8292210
TI  - Outcome of children with prolonged unconsciousness and vegetative states.
AB  - The outcomes of 60 children unconscious for 90 days or longer following acquired
      brain injury are reported. Eight children who died had remained in persistent
      vegetative states. As expected, most neurologic improvement occurred within the
      first year after injury, although some delayed improvements were observed.
      Outcomes were strongly correlated with causes of brain injury. Better cognitive
      and motor function was observed with nonanoxic injuries. No child in this report
      with anoxic brain injury regained functional cognitive or motor skills, although
      3 became socially responsive. The remarkable contrast with adults following
      acquired brain injury is the significantly longer survival of children. The only
      children who died had remained in persistent vegetative states.

PMID- 8292209
TI  - Bilateral striatal lesions in childhood.
AB  - From 1983 to 1991, 13 patients were identified with a clinical radiologic
      association characterized by acute or persistent neurologic dysfunction and
      bilateral lesions in the basal ganglia region demonstrated by ultrasound,
      computed tomography, or magnetic resonance imaging. Initial clinical
      manifestations of this group of patients were characterized by extrapyramidal
      signs (i.e., dystonia 9, hypotonia 2, athetosis 1, rigidity 1), altered state of
      consciousness in 5, and seizures in 3. The outcomes of most of these patients
      were poor: 10 had motor sequelae, 9 cognitive impairment, and 4 died. The
      outcomes of 2 patients, however, were much better than what was expected from the
      initial presentation. Based on current and previous reports, the diagnostic
      approach and classification of patients with neurologic dysfunction and bilateral
      striatal lesions are presented.

PMID- 8292211
TI  - Electroretinography in congenital idiopathic nystagmus.
AB  - Ganzfeld electroretinograms were recorded from 105 consecutive patients
      clinically believed to have congenital idiopathic nystagmus. Retinal disease
      causing congenital nystagmus was diagnosed in 59 patients (56%).
      Electroretinographic evaluation of children with nystagmus and apparently normal
      eyes has both diagnostic and prognostic value. In patients with congenital
      nystagmus with a normal ocular examination, a diagnosis of congenital idiopathic
      nystagmus cannot be inferred without electroretinographic evidence of normal
      retinal function.

PMID- 8292212
TI  - Is demyelination a feature of maple syrup urine disease?
AB  - To determine whether disturbance of myelination is a pathophysiologic feature in
      patients with treated maple syrup urine disease (MSUD), neurophysiologic studies
      were performed in 10 MSUD patients ages 4-16 years. Afferent and efferent
      pathways were studied by visual evoked potentials, somatosensory evoked
      potentials, motor evoked potentials, stance-stabilizing reflexes, and peripheral
      nerve conduction velocity. Magnetic resonance imaging was used to detect possible
      cerebral white matter abnormalities. Visual evoked potentials were normal in all
      patients. There was only slight prolongation of central afferent and efferent
      conduction times and the long latency component of the stance-stabilizing
      reflexes. Peripheral nerve conduction studies revealed reduced sensory nerve
      conduction velocity in 3 patients. The neurophysiologic findings were not
      consistently correlated to the neurologic outcome of the patients. Magnetic
      resonance imaging did not reveal major abnormalities and demonstrated bilateral
      periventricular high intensity periventricular signals on T2-weighted images in 4
      of 10 patients. It is concluded that dysmyelination is not a major
      pathophysiologic feature in patients with MSUD.

PMID- 8292213
TI  - Neurologic profiles of infants and children after perinatal stroke.
AB  - Twenty-nine children with a single, unilateral cerebral infarct acquired pre- or
      perinatally were examined subsequently for an average of 43 months. No consistent
      pre- or perinatal events were identified to explain the occurrence of the stroke.
      The children acquired motor milestones at nearly expected times, even in the
      presence of hemiparesis. In children older than 2 years of age, I.Q. scores all
      were within the normal range. More than one-half of the children experienced
      seizures at some time during the follow-up period. Good intellectual and
      functional motor outcome can be expected in children with isolated perinatal
      stroke.

PMID- 8292214
TI  - Auditory evoked responses in Krabbe disease.
AB  - Serial auditory evoked responses were investigated in 3 children with Krabbe
      disease. Auditory brainstem responses revealed prolongation of each wave
      component and interpeak latency with decreased amplitudes in later components
      which finally disappeared except for wave I. Long-latency auditory responses
      (LLRs) persisted in the advanced stage when all wave components of middle-latency
      auditory responses (MLRs) had disappeared. The results of auditory brainstem
      responses and MLRs are compatible with magnetic resonance imaging findings and a
      review of pathologic findings in Krabbe disease, including extensive involvement
      of brainstem and subcortical structures. It is suggested that the source of LLR
      waves is different from that of MLR because of the persistent existence of LLR
      waves. It is speculated that the cerebral cortex and/or subcortical U fibers,
      which are spared in Krabbe disease, have an important role in generating LLR wave
      components.

PMID- 8292215
TI  - Successful mitral valve replacement for MELAS.
AB  - Successful mitral valve replacement for severe mitral regurgitation in a patient
      with mitochondrial encephalomyopathy is reported. Renal failure due to low
      cardiac output improved dramatically after mitral valve replacement and he was
      discharged 10 weeks after surgery. The surgical indication and timing for
      valvular dysfunction in patients with mitochondrial cardiomyopathy are discussed.

PMID- 8292216
TI  - Benign abducens nerve palsy of childhood.
AB  - Benign acquired isolated abducens nerve palsy in infants and children is a rare
      condition and recurrence is even less common. The diagnosis is essentially one of
      exclusion. Six children (1 male, 5 females) are reported with benign isolated
      abducens nerve palsy, ranging in age from 8 months to 12 years (median: 5.5
      years). The left side was affected in all patients. Recovery occurred within 18
      55 days, but 3 patients developed recurrence with complete resolution of symptoms
      within 10-21 days.

PMID- 8292217
TI  - Moyamoya syndrome in a patient with Down syndrome presenting with chorea.
AB  - An 11-year-old girl with Down syndrome is reported with moyamoya syndrome; she
      presented with chorea and mental regression, but had no hemiplegia or
      convulsions. Magnetic resonance imaging and magnetic resonance angiography were
      valuable for diagnosis of moyamoya syndrome. It is suggested that moyamoya
      syndrome be considered as a possible cause of involuntary movements in Down
      syndrome patients.

PMID- 8292218
TI  - Flaccid paraplegia as complication of umbilical artery catheterization.
AB  - Two patients are described who acquired neonatal flaccid paraplegia associated
      with umbilical artery catheterization. Neurophysiologic studies demonstrated
      spinal cord injury at the level of T7 and below in Patient 1 and at the level of
      L1 and below in Patient 2. Deferred spinal cord magnetic resonance imaging
      confirmed regional spinal cord atrophy. In Patient 1, the syndrome was presumed
      to be triggered by a spasm or embolism of the Adamkiewicz artery due to movement
      of the umbilical artery catheter. In Patient 2, the spinal cord ischemia was
      probably caused by an embolic mechanism.

PMID- 8292219
TI  - Paroxysmal pain as sole manifestation of seizures.
AB  - A developmentally normal 4-year-old white female who presented with pain in the
      right hand as the only manifestation of epilepsy is reported. Two years later,
      she developed complex partial seizures following right-hand pain. Computed
      tomography and magnetic resonance imaging were unremarkable. Prolonged ambulatory
      electroencephalography (EEG) as well as video-EEGs with ictal pain episodes
      failed to reveal abnormalities. Only a full night video-EEG performed after
      antiepileptic drug withdrawal demonstrated 2 right-hand pain episodes followed by
      a complex partial seizure with ictal epileptiform activity on the scalp EEG in
      the left parasagittal area, rapidly generalized and interictal discharges in the
      C3-P3 area. This patient had a very unusual presentation of epilepsy.

PMID- 8292220
TI  - Rapid cataract formation in Marinesco-Sjogren syndrome.

PMID- 8292221
TI  - PET does not eliminate need for extraoperative, intracranial monitoring in
      pediatric epilepsy surgery.

PMID- 8292222
TI  - PET in preoperative evaluation of intractable epilepsy.

PMID- 8292223
TI  - Large mirror movements of upper extremities in Williams syndrome.

PMID- 8292224
TI  - HIV seropositivity among female prostitutes and nonprostitutes: obstetric and
      perinatal implications.
AB  - Serum samples totaling 600 were obtained from female prostitutes (300) resident
      in different hotels in Lagos, Nigeria and nonprostitutes (300) attending
      different health centers for routine check-up in Lagos, Nigeria. Sera obtained
      were screened for the prevalence of HIV seropositivity among prostitutes in
      comparison with nonprostitutes by the enzyme linked immunosorbent assay (ELISA)
      using the Abbott test kits as recommended by the manufacturers. Positive sera
      were subjected to confirmatory testing using the Western Blot test-New Lav Blot I
      and II. Our results revealed that of the 300 prostitutes and nonprostitutes
      screened, 50 (16.67%) and 6 (2%) were HIV seropositive, respectively, and the
      difference was statistically significant (P < 0.01). For antibody to HIV-1, 44
      (88%) and 5 (83%) of the positive cases recorded among prostitutes and
      nonprostitutes were seropositive. Four (8%) and one (16.67%) of the positive
      cases were HIV-2 seropositive for prostitutes and nonprostitutes, respectively.
      Only 2 (4%) of the positive samples from prostitutes showed reactivities with HIV
      1 and HIV-2 (simultaneous infection or dual reactivity). Incidence of the dual
      reactivity was not recorded among the nonprostitutes screened. This study is
      expected to provide baseline data on HIV seropositivities among prostitutes and
      nonprostitutes in Nigeria. The biomedical application of this study is that it
      will also serve as strong evidence to indicate the high prevalence of HIV
      seropositivity among prostitutes in order to attract government intervention to
      step-up control measures.

PMID- 8292225
TI  - Modulation of the immunosuppressive activity of CKS-17, a synthetic retroviral
      envelope peptide, by muramyl dipeptide.
AB  - CKS-17, a heptadecapeptide corresponding to a region highly conserved in
      retroviral transmembrane proteins is known to be immunosuppressive both in vitro
      and in vivo when conjugated to a carrier protein. Here we examined the effect of
      the synthetic adjuvant muramyl dipeptide (MDP) on the immunosuppressive
      properties of CKS-17-BSA in vitro. MDP was found to abrogate CKS-17-BSA-induced
      inhibition of both IgM plaque-forming cell responses and antitetanus toxin IgG
      secretion by BALB/c mouse spleen cells immunized in vivo and in vitro by sheep
      red blood cells and tetanus toxoid, respectively. In contrast, the CKS-17-BSA
      suppression of concanavalin A-induced splenocyte proliferation was not abrogated
      by MDP. The data suggest that muramyl peptides could be useful as immunoadjuvants
      for vaccines against retrovirus-associated immunosuppressive diseases.

PMID- 8292226
TI  - The in vitro infection of the hematopoietic stroma of trout kidney by hemorrhagic
      septicemia rhabdovirus.
AB  - Viral hemorrhagic septicaemia virus (VHSV) infected the hematopoietic stromal
      cells (7,8) derived from pronephritic tissue of the rainbow trout, Oncorhynchuss
      mykiss, W., at their ninth passage in vitro. Viral infection resulted in the
      development of lytic cytopathic effects on confluent in vitro tridimensional
      network stromal cell cultures. Replication of VHSV in the stromal cell cultures
      was demonstrated by the increase in infectivity by epithelioma papulosum cyprini
      (EPC) cell culture assays and by the increase of the nucleoprotein antigen of
      VHSV by ELISA. By using anti-VHSV monoclonal antibodies (MAbs), flow cytometry
      studies demonstrated that only the infected stromal cells contained cytoplasmic
      viral antigens. The lytic infection of trout hematopoietic stromal cells in vitro
      could be relevant to the hemorrhagic pathology seen in the kidney of fish
      infected with VHSV.

PMID- 8292227
TI  - IFN-gamma production in response to neuropathogenic Cas-Br-M murine leukemia
      virus infection.
AB  - T cell-mediated production of IFN-gamma followed infection of adult, but not
      neonatal NFS/N mice with Cas-Br-M murine leukemia virus (Cas). The IFN-gamma
      response was associated with the appearance of CTL specific for Cas and with age
      dependent resistance to neurologic disease. While both immune responses were
      mediated by a CD8-enriched population of T cells, IFN-gamma did not play a role
      in the activation of the Cas-specific CTL response. However, when given
      exogenously, IFN-gamma delayed the onset and reduced the incidence of Cas-induced
      neurologic disease. These data suggest that the IFN-gamma response to Cas
      infection may be an important host defense mechanism whose effects on virus
      replication and neurologic disease expression are independent of its effect on
      Cas-specific CTL.

PMID- 8292228
TI  - Thermogenic response to feeding in severely burned patients: relation to resting
      metabolic rate.
AB  - Energy expenditure (EE) was measured one to five times by indirect calorimetry
      for 1 h after an overnight fast, and for 2 h after starting feeding in 19
      severely burned patients (TBSA > 20 per cent) for a total of 36 tests. Twelve
      tube-fed volunteers served as controls. Thermogenic response to feeding (TRF) was
      calculated as the percentage of energy intake and hypermetabolism as the
      percentage of values obtained with the Harris-Benedict formula (%HB). Measured
      energy expenditure values were compared with values given by three predicting
      formulae. TRF was present in 10 out of the 33 measurements. Fasting EE was not
      different between the tests with and without TRF, but %HB was different between
      the two groups: 121.1 +/- 25.8 vs 157.8 +/- 32.0 per cent (tests with and without
      TRF, respectively (P < 0.01)). TRF was always absent when %HB was higher than 50.
      When TRF was present it was not statistically different from the control values.
      None of the three predicting formulae gave values within 10 per cent of the
      measured values in more than 25 per cent of the patients. We conclude that TRF is
      suppressed in burned patients with marked hypermetabolism, and that EE measured
      in the fed state reflects resting expenditure accurately in these patients. In
      addition, EE cannot be predicted from existing formulae.

PMID- 8292229
TI  - Absence of change in hepatic lactate metabolism after burn injury.
AB  - In response to severe injury, extraordinary quantities of lactate that are
      released from the peripheral tissues serve as substrate for hepatic
      gluconeogenesis. It is possible that as a result of burn injury, reaction
      kinetics involving lactate could be directly changed within the liver. The
      metabolic fate of [U-14C]lactate was examined in vitro in fresh liver slices
      after a 20 per cent total body surface area injury. Glucose and CO2 were produced
      in vitro by the liver tissues after the injury and no differences were seen in
      the metabolism of these substrates between the injured and control animals. These
      findings suggest that the intrinsic enzymatic processes within the liver are not
      directly altered by injury itself or by any of the associated inflammatory
      mediators which appear early after burns.

PMID- 8292230
TI  - Human postburn oedema measured with the impression method.
AB  - The course of tissue swelling in human non-injured skin after burn injury was
      investigated with a non-invasive impression method that measures force and tissue
      fluid translocation during mechanical compression of the skin. Time-dependent
      changes in the fluid translocation and the interstitial-pressure related to
      impression force were measured on 11 occasions, during 3 weeks, in seven patients
      postburn. A mathematical model was fitted to the impression force curves and the
      parameters of the model depicted the time-dependent compartmental fluid shift in
      the postburn generalized oedema. Tissue fluid translocation increased
      significantly (P < 0.05) up to a maximum value after 6 days postburn and declined
      thereafter. This indicated a continuous increase in the generalized postburn
      oedema for the first 6 days postburn. Impression force at 3 weeks postburn was
      significantly lower (P < 0.001) as compared with the half-day postburn value,
      indicating an increased tissue pressure during the first days postburn. Parameter
      analysis indicated a flux of water-like fluid from the vasculature to the
      interstitial space during the first 6 days postburn. The spread of the values
      registered between different measurement sites was, however, large.

PMID- 8292231
TI  - New laser Doppler scanner, a valuable adjunct in burn depth assessment.
AB  - A new medical instrument is presented that produces a doppler blood flow image
      from a laser beam in a raster pattern and the results of a pilot study which
      shows this technique to be highly accurate in assessing burn depth is described.

PMID- 8292232
TI  - Who should lead the burn care team?

PMID- 8292233
TI  - Young, scarred children and their mothers--a short-term investigation into the
      practical, psychological and social implications of thermal injury to the
      preschool child. Part I: Implications for the mother.
AB  - A short-term, prospective study, using both quantitative and qualitative methods,
      was designed to determine the practical, psychological and social implications of
      thermal injury resulting in scarring, for the mothers of thermally injured
      children, during the 6 months following the child's discharge from hospital.
      Mothers of 57 thermally injured children under 5 years of age were interviewed
      whilst the child was in hospital and at home, at 1 week, 2 months and 6 months
      following hospital discharge. Thermal injuries ranged from 1 to 41 per cent of
      body surface area and all required skin grafting. Qualitative analysis of
      interview transcripts resulted in the development of a model of the mother's
      response--The Maternal Thermal Injury Response Pattern (MTIRP)--which describes a
      phasic pattern of general response categories. The mothers' psychiatric morbidity
      was measured using Goldberg's (1978) 60-item General Health Questionnaire (GHQ).
      The mean of the mothers' total GHQ scores was 2.42 for the retrospective, pre
      injury score, 24.5 at the hospital interview and 5.96 at 6 months following the
      child's discharge from hospital. In conclusion, the mother is a neglected victim
      of a young child's thermal injury. Use of the MTIRP as an educational tool for
      carers would promote increased understanding and, thus, more appropriate support.

PMID- 8292234
TI  - Young, scarred children and their mothers--a short-term investigation into the
      practical, psychological and social implications of thermal injury to the
      preschool child. Part II: implications for the child.
AB  - A short-term, prospective study, using both quantitative and qualitative methods,
      was designed to determine the practical, psychological and social implications of
      thermal injury resulting in scarring for children under 5 years of age, during
      the 6 months following the child's discharge from hospital. Mothers of 57
      children (whose thermal injuries ranged from 1 to 41 per cent of body surface
      area and who all required skin grafting) were interviewed whilst the child was in
      hospital and at home, at 1 week, 2 months and 6 months following hospital
      discharge. From the mothers' descriptions, four categories of child behavioural
      response to thermal injury and hospitalization were identified. In the first week
      after discharge from the burns unit, 56 per cent (32/57) of children displayed
      minor or major disturbed behaviour, which had reduced to 19.3 per cent (11/57) by
      the 6-month interview. There were many reported physical and practical problems
      associated with the thermal injury and after-care. The MacGregor Deformity Scale
      was employed to assess the child's appearance. The child behaviour test scores
      (S. Jenkins et al. J. Child Psychol. Psychiatr. 1980; 21: 5; N. Richman et al.
      Pre-school to School-A Behavioural Study. 1982; Academic) demonstrated a similar
      progression of behavioural responses as the qualitative data, and, furthermore,
      indicated that the children under 2 years of age seemed to be affected for a more
      prolonged period.

PMID- 8292235
TI  - Young, scarred children and their mothers--a short-term investigation into the
      practical, psychological and social implications of thermal injury to the
      preschool child. Part III: Factors influencing outcome responses.
AB  - The thermal injury, personal and social factors affecting the short-term outcome
      responses of thermally injured children under 5 years of age and their mothers
      are reported. Statistical analysis of factors influencing the mother and child
      outcome responses uses data from serial interviews with mothers of 57 thermally
      injured children which took place whilst the child was in hospital, and at home,
      at 1 week, 2 months and 6 months following hospital discharge. A relationship was
      found between the child's behaviour and the mother's outcome response at 6
      months. Essentially, for the mother, the qualitative outcome response of the
      Maternal Thermal Injury Response Pattern was associated with the severity of the
      child's thermal injury and the quantitative General Health Questionnaire scores
      were associated with a previous tendency to depression and increased stress on
      the mother existing prior to the accident. For the child, no thermal injury
      factor appeared to affect behavioural outcome. The child was disturbed behaviour
      following a thermal injury, however, was more likely to have a mother with a
      history of depression, and added stress (lower socioeconomic status, and
      additional worries) and have a mother who was blamed for the accident. Thus,
      mothers whose child has a more severe thermal injury will take longer to come to
      terms with it ('rationalize' the thermal injury) and those mothers who were most
      stressed prior to the accident and who had a previous tendency to depression,
      will have more psychiatric morbidity (a higher GHQ score) as a result. Both these
      groups will require particular support.

PMID- 8292236
TI  - The problem of dehydration and healing of burn wounds.
AB  - In an experiment on rats, a partial thickness burn wound 20 mm in diameter was
      produced on the dorsum. Half the wound area was left untreated, the other half
      painted with elastic collodion. Examination on the 10th day following the
      intervention confirmed that prevention of dehydration can save a good proportion
      of thermally damaged tissue. It was also shown that prevention of dehydration
      results in a marked delay in wound healing.

PMID- 8292237
TI  - Burn injuries in the elderly.
AB  - This study has shown that elderly males were more likely to be admitted to the
      Royal Brisbane Hospital Burns Unit than females. No high-risk period of the day,
      week or year could be identified for this group. Flame burns and scalds were most
      common as was the association with cooking and bathing activities. Predisposing
      factors were found to be common in the elderly burn population. Prevention
      programmes need to be directed to the home with safer cooking facilities and
      lower temperature or temperature outlet controls to lessen bathing scalds, as
      these patients found it difficult to escape a hot bath. Mortality rates were
      related to the percentage total body surface area burned and inhalation injury,
      and were well predicted by the Burn Severity Index. Complications were mainly
      pneumonias and venous thrombosis and reflect the need in this age group of
      maintaining active mobility and a quick resolution of the burn injury. Good
      nutrition, often lacking in this age group, must be maintained, along with
      meticulous wound care if infection is to be prevented. Early wound coverage is
      vital to prevent sepsis. Our approach is towards an early skin grafting programme
      while the patient is fit. This is aggressive, with as much skin coverage as
      possible, before the patient's condition deteriorates. Every effort is made to
      maintain the patient's health as near normal as possible. However, if
      deterioration occurs, then the patient is supported and grafting delayed until
      the patient is again fit for surgery. When this study was undertaken, it was
      hoped that an answer to the controversial subject of early versus late surgery
      could be answered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292238
TI  - Analysis of 155 patients with chemical injury: a 5-year experience.
AB  - From July 1986 to June 1991, 155 patients were treated in our department for
      various chemical burn injuries. The experience over the 5-year period is
      reviewed. Among these patients, 109 patients were between 20 and 40 years of age
      and accounted for 70.3 per cent of all chemical burn patients. It is suggested
      that chemical burns are very common in people of working age. Chemical burn
      manifestations were unlike those of thermal injury. The scene of injury, type of
      chemical agent, age of patients, clinical manifestation and management of the
      burn surface are discussed. Although the patients were given the same physical
      therapy, early tangential or full thickness excision and immediate autografting
      yielded better results than conservative treatment and shortened hospital stay.

PMID- 8292239
TI  - Optimizing skin graft take in children's hand burns--the use of silastic foam
      dressings.
AB  - The use of silastic foam as a surgical dressing in 15 children with full
      thickness burns to the hand is described. Silastic foam is a safe, easy and
      effective means of dressing the hand following surgery. It is rigid enough to act
      as a splint, and at the same time is deformable and accommodates postoperative
      swelling.

PMID- 8292240
TI  - Entrapment against radiators--an underestimated burn hazard to the elderly.
AB  - Five cases of burns caused by residents of nursing homes falling out of bed and
      becoming trapped against radiators or hot pipes are reported. The current
      guidelines for nursing homes in relation to heating surfaces are reviewed and
      recommendations are made on how this hazard can be avoided.

PMID- 8292241
TI  - Requirements for cross-matched blood in burns surgery.
AB  - This prospective study of operative blood loss during burns surgery in 142
      patients demonstrated no significant difference between the loss seen during
      layered excision and grafting up to 7 days after thermal injury and that observed
      during formal excision and grafting from 8 days onward. There was no significant
      difference between the blood loss in infants under 3 years old and that seen in
      older children and adults. From the data obtained, a graphical 'tariff' has been
      constructed for both children up to 20 kg and older children and adults over 20
      kg in weight for the ordering of cross-matched blood for perioperative
      transfusion. It is suggested that the use of this tariff will help to strike a
      balance between the wasteful overprovision and dangerous underprovision of cross
      matched blood for burns surgery.

PMID- 8292242
TI  - Concentration of orally administered antimicrobial agent in burn scar tissue,
      granulation tissue, normal skin and serum.
AB  - Tissue and serum concentrations of orally administered ofloxacin were measured
      using high performance liquid chromatography. From 56 patients who received 200
      mg of ofloxacin prior to surgery, 103 specimens including 48 of serum, 32 of scar
      tissue, 18 of normal skin and five of granulation tissue were harvested between 2
      and 3 h after administration. The ofloxacin values were 1798.6 +/- 1125.5 ng/g in
      the granulation tissue followed by 1525.5 +/- 1002.7 ng/ml in the serum, 1450.0
      +/- 1011.3 ng/g in the scar tissue and 1092.8 +/- 593.3 ng/g in normal skin.
      There was no statistically significant difference between the ofloxacin
      concentrations in those four specimens by ANOVA test.

PMID- 8292243
TI  - Burn survivors and the Americans with Disabilities Act.
AB  - In this article the major provisions of the recently revised Americans with
      Disabilities Act (ADA) and its application to burn survivors are explained. For
      professionals working with this population, the ADA is a model for dealing with
      issues of follow-up and long-term patient adjustment. An overview of previous
      laws applying to the rights of the disabled in the USA is followed by a brief
      history of the ADA's development. Each of the five major provisions of the act is
      discussed in detail. Case studies of burn survivors are used to demonstrate the
      way in which knowledge of the ADA can be used to anticipate and deal with
      potential complications of re-entry after hospitalization.

PMID- 8292244
TI  - Electrical burns caused by fishing rod contact with overhead electric cables: a
      potential hazard to fishermen.
AB  - Three patients were admitted to the Burns Unit at Newcastle General Hospital
      suffering from varying degrees of electrical burn injuries. All were fishermen
      whose injuries had been caused by their highly conductive carbon fibre fishing
      rods touching overhead high voltage electrical cables. This paper also describes
      the information available to fishermen to assist in the prevention of this type
      of injury.

PMID- 8292245
TI  - Acute colonic pseudo-obstruction in a burn patient.
AB  - Acute colonic pseudo-obstruction as a syndrome was first described by Ogilvie in
      1948 (Br. Med J. 2, 671). It is characterized by colonic dilatation with no
      mechanical cause which affects critically ill patients. As a result of this
      complication the prognosis worsens. Initially there are few clinical symptoms,
      but subsequently colonic obstruction develops which, if not treated, can cause
      perforation of the caecum resulting in a high mortality rate. The treatment
      includes decompression via rectal and nasogastric probes, colonoscopy and
      caecostomy.

PMID- 8292246
TI  - Pop Tarts--so hot they scald.

PMID- 8292247
TI  - ECG monitoring in severely burned patients--a simple solution!

PMID- 8292248
TI  - Chronic infusions of GABA into the medial prefrontal cortex induce spatial
      alternation deficits in aged rats.
AB  - It has been proposed that functions associated with the prefrontal cortex could
      change as a consequence of aging. Previous experiments in young rats have
      demonstrated that anatomical lesions or chronic GABA infusions into this area
      produce deficits in spatial delayed alternation tasks. The present study examines
      the effect of chronic (7 days) GABA or saline infusion into the prefrontal cortex
      on the performance of delayed alternation task in old rats (24 months). The
      results suggested that aged rats needed more sessions to acquire the delayed
      alternation task. GABA infusions into the prefrontal cortex produced deficits in
      spatial alternation tasks similar to those previously observed in young rats.
      Performance rapidly recovered after the infusion period. Histological analysis
      showed similar lesion size in both groups. The results suggest that aged
      prefrontal cortex and/or related areas participating in the acquisition of the
      delayed alternation task are more sensitive to aging processes. Furthermore, the
      prefrontal cortex is important for the retention of a previously learned spatial
      delayed alternation task. The structures involved in functional recovery from
      these deficits appear to be fully functional in aged rats.

PMID- 8292249
TI  - Maudsley rat strains, selected for differences in emotional responses, differ in
      behavioral response to clonidine and in [125I]clonidine binding in the locus
      coeruleus.
AB  - Maudsley rats, selectively inbred for emotionality for over sixty generations,
      differ in reactivity to stress, both at the peripheral level and within the
      central noradrenergic system. The present experiments examine to what extent
      these central differences might be due to differences in the inhibitory processes
      mediated by alpha 2 autoreceptors within the locus coeruleus. Maudsley reactive
      rats (MRs), the strain which showed a much higher central noradrenergic response
      to immobilisation stress, required higher doses of the alpha 2 receptor agonist,
      clonidine, to induce behavioral sedation than the Maudsley non-reactive rats
      (MNRA). Autoradiographic studies showed a significantly higher level of binding
      of 125iodeclonidine in the locus coeruleus of the MNRAs compared to the MRs,
      indicating that the former had more alpha 2 receptors and/or these receptors had
      a greater affinity for the agonist. Thus autoinhibitory processes within the
      locus coeruleus are different in the two strains, which could account for the
      differences in reactivity to stress seen in the biochemical and behavioral
      studies.

PMID- 8292250
TI  - Adenosine receptor agonists inhibit TRH-induced behaviour in rabbits: evidence
      for a main role of striatal A2 receptors.
AB  - The present article studies the influence of A2 (CGS 21680) and A1 (CPA)
      adenosine receptor agonists on TRH-induced behavioural excitation in rabbits. The
      results show that CGS 21680 was the most effective drug when administered into
      the nucleus caudate, while its intracerebroventricular (i.c.v.) administration
      did not influence the effects induced by TRH. Conversely, CPA exerted the same,
      slight effects after either intracaudate or i.c.v. administration. Since TRH
      induced excitatory effects can be regarded as dopamine-related behaviours, the
      present results further confirm that the adenosine system inhibits the
      behavioural effects due to dopaminergic activation. The major involvement of
      striatal A2 receptors in this effect of adenosine is also discussed.

PMID- 8292251
TI  - Optokinetic and pursuit system: a case report.
AB  - Several studies have demonstrated the importance of the pretectal Nucleus of the
      Optic Tract (NOT) and the Dorsal Terminal Nucleus of the accessory optic system
      (DTN) for the generation of horizontal optokinetic nystagmus (OKN). Although
      single unit data from trained rhesus monkey NOT/DTN cells are available it is
      still unclear if there is a link between the pursuit and the optokinetic system
      at this level of motion analysis. In order to address the question whether the
      NOT/DTN is important for the optokinetic as well as the pursuit system an
      electrolytic lesion was placed where NOT/DTN activity was recorded previously.
      The monkey was tested on optokinetic and pursuit paradigms. Immediately following
      the lesion the monkey performed a spontaneous nystagmus with slow phases directed
      away from the lesioned side. This spontaneous nystagmus persisted even during
      optokinetic stimulation in the opposite direction. During the first week
      postlesion the spontaneous nystagmus disappeared and the monkey regained the
      ability to perform optokinetic nystagmus toward the lesioned side. The gain of
      the mean slow phase eye velocity was, however, largely reduced for this stimulus
      direction. The onset of OKN following the onset of optokinetic stimulation was
      not affected by the lesion. During smooth pursuit the mean eye velocity was more
      reduced for pursuit towards the lesioned side. The resulting position error was
      compensated by an increase in the number of catch-up saccades. In addition to the
      confirmation of the well-known directional deficits of the optokinetic system
      caused by a lesion of the pretectum, a directional deficit in the pursuit system
      was demonstrated.

PMID- 8292252
TI  - Arousal following intra-preoptic area administration of naltrexone, ICI 174864 or
      nor-BNI in hibernating ground squirrels.
AB  - Experiments were performed from January 1 to 30 January, 1989. Drugs were
      administered to the preoptic area of hibernating ground squirrels through a
      chronically implanted cannula on the 2nd day of a torpor bout. When naltrexone
      (an antagonist of opioid receptor) was injected, part (naltrexone, 0.5 or 1
      microgram/microliter/32 min) or all (naltrexone, 2 micrograms/microliters/32 min)
      of the animals' body temperature was increased and they aroused from hibernation
      within 20 h after the injection. Further experiments showed that intra-preoptic
      area perfusion of 1 nmol of ICI 174864 (an antagonist of delta receptor) or nor
      BNI (an antagonist of kappa receptor), but not beta-FNA (an antagonist of mu
      receptor), were able to increase the body temperature of hibernating ground
      squirrels and arouse them from hibernation in 20 h after the injection. These
      results indicate that (1) opioid peptides in the preoptic area may be involved in
      the mechanisms of hibernation; (2) activation of delta and kappa receptors in the
      preoptic area is indispensable for the maintenance of hibernation in ground
      squirrels.

PMID- 8292253
TI  - An acute dose of delta 9-tetrahydrocannabinol affects behavioral and
      neurochemical indices of mesolimbic dopaminergic activity.
AB  - Cannabinoid consumption has been reported to affect several neurotransmitter
      systems and their related behaviors. The present study has been designed to
      examine cannabinoid effects on certain behaviors, which have been currently
      located in the limbic forebrain, in parallel to their effects on mesolimbic
      dopaminergic neurons. To this end, male rats treated with an oral dose of delta 9
      tetrahydrocannabinol (THC) or vehicle were used 1 h after treatment for two
      different behavioral tests or neurochemical analyses of mesolimbic dopaminergic
      activity. Treatments, behavioral tests and sacrifice were performed in the dark
      phase of photoperiod because it corresponds to the maximum behavioral expression
      in the rat. Behavioral tests were a dark-light emergence test, which allows
      measurements of emotional reactivity, and a socio-sexual approach behavior test,
      which allows measurements of sexual motivation and also of spontaneous and
      stereotypic activities. Neurochemical analyses consisted of measurements of
      dopamine (DA) and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents, tyrosine
      hydroxylase activity, in vitro DA release and number and affinity of D1 receptors
      in the limbic forebrain. Results were as follows. THC exposure markedly altered
      the pattern executed by the animals in both tests. Concretely, THC-exposed
      animals exhibited a low number of visits to an incentive female in addition to
      high time spent in the vicinity of an incentive male, both observed in the socio
      sexual approach behavior test, and an increased emergence latency to go out of a
      dark compartment in the dark-light emergence test. However, the fact that THC
      also decreased spontaneous activity and the frequency of rearing and self
      grooming behaviors, in addition to the observations of either low total number of
      visits to both incentive sexual areas or high escape latency to go out of a light
      compartment, when the animal is placed in this compartment, also suggest the
      possible existence of an accompanying motor deficit. These behavioral effects
      were accompanied by increases in DA and DOPAC contents and in D1 receptor density
      in the limbic forebrain and to a slight decrease in the pattern of K(+)-evoked DA
      release in vitro from perifused limbic fragments, with no changes in the
      remaining neurochemical parameters. Collectively, these results allow us to
      conclude that acute THC markedly altered the behavioral pattern executed by the
      animals in a socio-sexual approach behavior test and in a dark-light emergence
      test, presumably indicating loss of sexual motivation and increased emotionality,
      although also accompanied by motor deficiencies.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8292254
TI  - Gender-specific impairment on Morris water maze task after entorhinal cortex
      lesion.
AB  - After unilateral entorhinal cortex lesion, deficits on a working spatial memory
      Morris water maze task were examined in male and female rats to determine if
      gender differences exist in response to hippocampal deafferentation. Brain
      damaged males showed a persistent water maze deficit that persisted throughout
      the 10 days of testing. Brain-damaged females did not. The performance of the
      injured females was only slightly impaired relative to sham males and females,
      and was significantly better than males with EC damage. This lack of a water maze
      deficit in lesion females is hypothesized to be due either to gender differences
      in sprouting responses or to a more flexible use of multiple cues by females
      relative to males.

PMID- 8292255
TI  - Mesial temporal neurons in the macaque monkey with responses selective for
      aspects of social stimuli.
AB  - Primates possess a sophisticated cognitive ability to interpret and respond to
      the social actions of conspecifics. Neurons in the temporal lobes of macaque
      monkeys which are selective for the appearance and motions of conspecifics have
      been described previously; the results reported here indicate that pathways which
      integrate such information converge in mesial temporal regions. Single neuron
      data from an alert macaque viewing moving pictures of other monkeys engaged in a
      variety of behaviors are presented. Neurons in medial nuclei of the amygdala and
      adjacent mesial temporal cortex are sensitive to identity, movement, and high
      level aspects of depicted scenes.

PMID- 8292256
TI  - Neurological and behavioral effects of a unilateral frontal cortical lesions in
      fetal kittens. I. Brain morphology, movement, posture, and sensorimotor tests.
AB  - Nine fetal kittens sustained removal of the left frontal cortex during the last
      third of gestation (E 43-55) and were compared to animals sustaining a similar
      lesion postnatally (P 8-14) as well as to littermate controls. Starting after 6
      months of age the animals received a comprehensive battery of movement, posture
      and sensorimotor tests. The prenatal-lesioned cats performed worse in practically
      all 15 tests applied (significantly in 13 of them) compared to the neonatal
      lesioned cats. Impairments included contralateral paresis of the limbs and face,
      defective limb placing reactions (with almost absence of the contact components)
      and a slight extensor hypertonus; tactile hypoesthesia in the contralateral face
      and hind paw; a bias not to use the contralateral forepaw in a food retrieval
      task, and an ipsilateral body turning bias. The neonatal-lesioned animals only
      showed minor defects in the contact components of the limb placing reactions and
      a tendency to a body turning bias. Morphologically, the brains of the prenatal
      lesioned cats, but not of neonatal-lesioned or intact control cats, showed
      bilateral disruption of the cortical sulcal and gyral patterns, shrinkage of the
      ipsilateral hemisphere, and reduction in volume of the ipsilateral thalamus and
      cortex. We concluded, contrary to expectations, that the consequences of a
      prenatal brain lesion in the cat are worse than when a similar lesion is
      sustained neonatally.

PMID- 8292257
TI  - Neurological and behavioral effects of a unilateral frontal cortical lesion in
      fetal kittens. II. Visual system tests, and proposing an "optimal developmental
      period" for lesion effects.
AB  - Nine fetal kittens sustained removal of the left frontal cortex during the last
      third of gestation (E 43-55) and were compared to animals sustaining a similar
      lesion postnatally (P 8-14) as well as to intact littermates. Beginning after 6
      months of age, the animals' visual field and depth perception were assessed. In
      addition, pupil size as well as eye alignment were measured. On two visual field
      tests the fetal-lesioned cats showed test dependent decrements for some angles of
      vision. In terms of depth perception, only the prenatal-lesioned animals showed a
      higher binocular threshold; they also showed ocular misalignment which may have
      contributed to their depth perception impairment. Moreover, these animals had a
      larger ipsilateral pupil. The neonatal-lesioned animals were like normal cats for
      all tests and measurements. We conclude that, as for the tests reported in the
      preceding paper, the outcome for visual related behaviors of a prenatal frontal
      cortical lesion in the cat is also worse than that of a similar lesion sustained
      neonatally. Dysgenetic anatomical changes of the visual system induced indirectly
      by the frontal lesion are proposed as a possible explanation for these age-at
      lesion differences. Based on the present work as well as on the literature, we
      propose the existence of an "optimal developmental period" for the best
      behavioral and anatomical outcome of perinatal brain lesions. We argue that this
      concept fits contemporary data and can better explain the different age-at-lesion
      effects of brain injury across animals species than the "Kennard Principle" (or
      "infant-lesion effect").

PMID- 8292258
TI  - Behavioral responses induced by electrical stimulation of the caudate nucleus in
      freely moving cats.
AB  - The caudate nucleus and adjacent structures of 26 freely moving cats were
      stimulated through multiwire electrodes chronically implanted. Two main effects
      here observed with trains of pulses of high frequency (100 Hz) and short duration
      (1 s): (1) contralateral head turning and (2) arrest reaction, which was
      associated with crouching and escape behavior. The responses follow a certain
      topographic distribution. Head turning was elicited with the lowest mean
      threshold in sites located in the internal two-thirds and caudal region of the
      caudate nucleus, while the arrest reaction was elicited from the ventromedial
      region of the caudate and adjacent nucleus accumbens. Stimulation of the corpus
      callosum and internal capsule produces postural instability, ventral flexion of
      the head and flexion of the contralateral limb. The extra-caudate responses were
      accompanied by contralateral head turning when the stimulated points were near of
      the caudate border. Experimental evidence suggested that striatal responses were
      not due to current spread to adjacent structures or to activation of corticofugal
      fibers. The head rotation was suppressed following interruption of the
      ipsilateral striatal outflow by electrolytic lesion of the globus pallidus and
      adjacent internal capsule. The chemical lesion of the substantia nigra and the
      ventral pallidum produced a significant increase in the stimulation threshold for
      head turning and arrest reaction, respectively. These results suggest a
      topographic arrangement of the responses evoked by electrical stimulation of the
      caudate nucleus in the cat, which are mediated by the substantia nigra pars
      reticulata and the ventral pallidum.

PMID- 8292259
TI  - The variable genes of the human immunoglobulin kappa locus.

PMID- 8292260
TI  - The covalent linkage of secretory component to IgA. Structure of sIgA.
AB  - Immunoglobulin A which is secreted into external fluids is synthesized in plasma
      cells as an (IgA)2-J-chain complex. This complex docks on to the
      polyimmunoglobulin receptor which is located at the basolateral surface of
      epithelial cells. After docking the (IgA)2-J-receptor complex is internalized and
      processed. The polyimmunoglobulin receptor loses its C-terminal tail and thus
      becomes the secretory component. This secretory component is then covalently
      linked to the (IgA)2-J-chain complex by a disulfide bond, and protects the so
      formed sIgA from denaturation and proteolysis in external fluids. In order to
      establish this disulfide bond between IgA and the secretory component, sIgA,
      purified from human colostrum, was subjected to several enzymatic and chemical
      fragmentation reactions. One of the resulting polypeptides allowed us to
      characterize the covalent linkage of the secretory component to IgA in sIgA. IgA
      was found to be covalently linked to the secretory piece by a single disulfide
      bond between Cys 311 of one alpha-chain and Cys 467 of the secretory component.
      Cys 501 of the secretory component and Cys 311 of the other alpha-chain are
      blocked by cysteines. With this last paper of a series the structure of an entire
      sIgA molecule has been elucidated.

PMID- 8292261
TI  - Gel-immobilized heparin-binding lectin as sensitive sensor for certain groups of
      charge-bearing carbohydrates.
AB  - The specificity of lectins to carbohydrate moieties in principle enables them to
      serve as sensors for sugars with ligand properties. However, experimental systems
      and parameters to measure this interaction need to be defined. On the basis of
      knowledge about temperature-sensitive volume changes of gels, composed of
      acrylamide derivatives, and about the influence of presence of charge-bearing
      groups within the gel on this behavior, we covalently immobilized a human heparin
      binding lectin into a gel matrix. Besides the lectin-carrying derivative N
      isopropylacrylamide and N,N'-methylenebisacrylamide are the monomeric
      constituents of the polymer. The lectin has been attached to divinyl sulfone
      activated N-hydroxymethylacrylamide. Several anionic sugar moieties are added to
      the solution, covering the gel pieces, and the mechanical response of the
      individual gel slices in dependence to stepwise temperature increases is
      automatically recorded with an electronic transducer at a sensitivity of 5
      mV/microns. Only carboxyl group-containing sugar moieties like glucuronic acid
      notably reduce the extent of the temperature-dependent gel shrinking as indicator
      for a protein-carbohydrate interaction. The individual slices are reuseable,
      emphasizing practical applications. This sensitive and automated assay concept
      with the covalently immobilized heparin-binding protein is supposed to be
      adaptable to other groups of lectins with specificity to anionic sugars like
      sialic acid-binding proteins.

PMID- 8292262
TI  - A note on the identity of porcine liver carboxylesterase and prolyl-beta
      naphthylamidase.
AB  - Prolyl-beta-naphthylamidase from porcine liver is compared with the two prevalent
      isoenzymes of pig liver carboxylesterase by isoelectrofocusing experiments and by
      inhibition studies with phenyl-methyl-sulfonyl fluoride. The results suggest that
      prolyl-beta-naphthylamidase is identical with the amide-cleaving isoenzyme of
      carboxylesterase, not with the usually predominant methyl butyrate-hydrolysing
      isoenzyme. It is questionable whether the recently published sequence of prolyl
      beta-naphthylamidase does belong to this enzyme or to the predominant
      carboxylesterase without amidase activity. Surprisingly, the amide-cleaving
      carboxylesterase isoenzymes from rat liver have almost no activity with prolyl
      beta-naphthylamide.

PMID- 8292264
TI  - Secondary fungal metabolites and their biological activities, IV. Synthesis of
      compounds with structural similarities to the toxic metabolites of the pathogenic
      fungus Heterobasidion annosum and investigation of their antibiotic activities.
AB  - A series of synthetic analogues of fomannoxin and fomajorin S, the toxic
      metabolites of the basidiomycete Heterobasidion annosum, was prepared in order to
      investigate which partial structures of the molecules are responsible for their
      biological activities. Of the compounds synthesized the five indane-2-acid
      derivatives 5-acetylindane-2-carboxylic acid (2), (+/-)5-formylindane-2
      carboxylic acid (3), (+/-)indane-2,5-dicarboxylic acid (4), (+/-)formyl-2
      methylindane-2-carboxylic acid (7) and 5-acetyl-indane-2,2-dicarboxylic acid (10)
      and 4-(2'-ethylbutyloxy)benzaldehyde (18) have not yet been described. Different
      biological test systems were employed to investigate the antibiotic activities of
      the synthesized analogues. The experimental results suggest that in the case of
      fomajorin S, the structural element essential for its toxicity is the 2-H- or 2
      methylindane 2-acid. From the results obtained with the synthetic analogues of
      fomannoxin, it is now evident that the toxicity of this fungal metabolite can be
      attributed to an aromatic ring with a carbonyl or carboxyl substituent combined
      with a branched lipophilic side chain in p-substitution.

PMID- 8292263
TI  - Microbial metabolism of quinoline and related compounds. XX. Quinaldic acid 4
      oxidoreductase from Pseudomonas sp. AK-2 compared to other procaryotic molybdenum
      containing hydroxylases.
AB  - Quinaldic acid 4-oxidoreductase from Pseudomonas sp. AK-2 catalyses the
      hydroxylation of quinoline 2-carboxylic (quinaldic acid) to 4-hydroxyquinoline 2
      carboxylic acid (kynurenic acid) with concomitant reduction of a suitable
      electron acceptor. An analogous hydroxylation in para-position relative to the N
      heteroatom was only recently described for quinaldine 4-oxidoreductase (de Beyer
      & Lingens, 1993, Biol. Chem. Hoppe-Seyler 374, 101-110) and for quinaldic acid 4
      oxidoreductase from Serratia marcescens 2CC-1 (Fetzner & Lingens, 1993, Biol.
      Chem. Hoppe-Seyler 374, 363-376). Quinaldic acid 4-oxidoreductase from
      Pseudomonas putida AK-2 was purified 78-fold to electrophoretic homogeneity with
      a recovery of 22%. The native enzyme (300 kDa) was composed of three subunits
      with molecular masses of 90, 34 and 20 kDa, indicating an alpha 2 beta 2 gamma 2
      structure. Quinaldic acid 4-oxidoreductase contained FAD, molybdenum, iron and
      acid-labile sulfur in a ratio of 2:2:8:8. Molybdenum is probably associated with
      molybdopterin cytosine dinucleotide as organic part of the pterin molybdenum
      cofactor. The absorption spectrum of quinaldic acid 4-oxido-reductase exhibited
      the typical features of a molybdo-iron/sulfur-flavoprotein, namely, maxima at 274
      nm, 340 nm and 450 nm, a shoulder at 550 nm, a ratio A280/A450 of 4.7 and a ratio
      A450/A550 of 3.5. The enzyme was susceptible to inactivation by methanol, sodium
      m-arsenite, p-hydroxymercuribenzoate, and potassium cyanide. Cyanide caused an
      alteration at 320 nm in the absorption spectrum, typical for the change in the
      coordination sphere of the molybdenum. Enzyme inactivated with cyanide was
      reactivated to 74% by incubation with sulfide. Thus, quinaldic acid 4
      oxidoreductase possesses a monooxo-monosulfido-type molybdenum center.

PMID- 8292265
TI  - Synthesis of phytochelatins by the continuous flow solid phase procedure.
AB  - A nona- and an undecapeptide corresponding to phytochelatins with the general
      structure H-[gamma-Glu-Cys]n-Gly-OH were each synthesized by the continuous flow
      solid phase method using two different methodologies. Fmoc-amino acid derivatives
      were used as precursors, and two different H2N-POE-PS supports were employed.
      Different procedures were used to remove Acm protecting groups from Cys residues.
      In a second synthesis, Acm groups were removed before cleavage of the peptides
      from the polymer supports. The partially protected peptides of the first
      synthesis were purified by preparative HPLC. The purity and identity of all the
      synthesized peptides were verified by analytical HPLC and IS-MS and in some cases
      by amino acid analysis.

PMID- 8292266
TI  - A study of siliceous pneumoconiosis in a desert area of Sunan County, Gansu
      Province, China.
AB  - Three hundred and ninety five residents in a desert area were examined with chest
      radiographs and 28 cases with siliceous pneumoconiosis were found. The prevalence
      of siliceous pneumoconiosis was 7.09%, and that over 40 years of age was 21%. The
      histological findings of lungs from a camel living in that area for 20 years also
      confirmed to have siliceous pneumoconiosis.

PMID- 8292267
TI  - Carbon disulphide induced sensitivity changes of rat anococcygeus muscle to
      noradrenaline (NA).
AB  - The sensitivity of rat anococcygeus muscle to noradrenaline (NA) was reduced
      following carbon disulphide (CS2) pretreatment. Preparations incubated in excess
      Ca++ (4.2 mmol.L-1) or Zero Ca++ (0.0 mmol.L-1) media showed decrease in
      sensitivity to NA. Reserpinization failed to induce supersensitivity to NA in any
      Mg++ concentration in the media. Reserpinized tissue in Mg++ free media with EDTA
      showed increased sensitivity while decreased sensitivity and maximum response to
      NA in Mg++ (1.2 mmol.L-1) and excess Mg++ (3.6m mol.L-1) concentration of the
      medium. In the presence of EDTA, the inhibition observed with CS2 in excess Mg++
      (3.6m mol.L-1) medium was comparatively much less in both non-reserpinized and
      reserpinized preparations. In normal Ca++ and its deficient medium decrease in
      sensitivity to CS2 and the relevant maximum response to NA were observed. In
      excess Ca++, the CS2 effect depressed corresponding to its maximal response to
      NA. Thus CS2 may be inhibiting responses to NA by interfering with Ca++
      utilization.

PMID- 8292268
TI  - Renal toxicity of nickel, sodium lauryl sulphate and their combination after
      dermal application in guinea pigs.
AB  - The guinea pigs were dermally exposed to nickel (Ni), sodium lauryl sulphate
      (SLS) and in their combination for 7 and 14 days. The exposure to Ni and SLS
      produced changes in enzymes and lipid peroxidation in kidney. The exposure to Ni
      or SLS depicted slight changes while combined exposure to Ni plus SLS exhibited
      more degenerative changes in kidney. The result of the study suggests that
      industrial workers and/or populations exposed simultaneously to Ni and SLS
      produces more damage to kidney.

PMID- 8292269
TI  - The inhibitory effect of Chinese tea and its polyphenols on in vitro and in vivo
      N-nitrosation.
AB  - The objective of this study is to evaluate the possible role of Chinese tea as a
      natural inhibitor of N-nitrosation, and to compare the relative inhibitory
      potency of various kinds of Chinese tea in vitro and in vivo. Studies on the
      inhibitory effect of 145 samples of Chinese tea on the formation of N
      nitrosomorpholine (NMOR) showed that the inhibitory potency of the 7 types of
      Chinese tea differed greatly, the average blocking rate of green tea (89.04%, n =
      60), crush, tear, and curl (CTC) black tea (86.99%, n = 13), brick tea (85.40%, n
      = 7), jasmine tea (84.99%, n = 21), Oolong tea (82.37%, n = 9), sun-dried tea
      (61.99%, n = 13) and Chinese Gongfu black tea (54.98%, n = 22), were positively
      correlated with their polyphenols contents. The inhibitory effect of green tea
      and black tea on endogenous N-nitrosation was also confirmed in 3 human volunteer
      experiments. Drinking tea after meal had a greater effect than drinking it before
      meal. It is concluded that Chinese tea can exert a relatively strong inhibitory
      potency for N-Nitroso compounds (NOC) formation both in vitro and in humans, and
      the active constituents may be related to their polyphenols contents, especially
      the tea catechin derivatives. The results also demonstrated that the amounts of
      NMOR formed in vitro depended on the molecular structure of tea catechin
      derivatives and their molar ratios to nitrite.

PMID- 8292270
TI  - Alpha-tocopherol concentrations in human milk from mothers of preterm and full
      term infants in China.
AB  - alpha-Tocopherol content in breast milk of 28 mothers who delivered preterm
      infants (preterm milk) and 43 mothers who delivered full-term infants (term milk)
      were measured. alpha-Tocopherol concentration in preterm milk did not differ
      significantly from that of term milk in the first 12 days of lactation (P >
      0.05). There is a higher alpha-tocopherol concentration in the early colostrum,
      however, it decreases with the lactational days significantly. The investigation
      suggests that early breast-feeding would be beneficial to the improvement of
      vitamin E intake in neonates during the early life.

PMID- 8292271
TI  - Adaptive response of wild and mutant type Synechococcus cedrorum to a
      polychlorinated pesticide-endosulfan.
AB  - The effect of endosulfan, a hexachlorinated pesticide, on growth, inorganic
      nitrogenous nutrient uptake (NO3-, NO2- and NH4+), change in pigmentation and
      glycogen content on wild type and chemically mutagenised cells of Synechococcus
      cedrorum was investigated. The pattern of response to pesticide stress in wild
      and mutant type was the same. Growth reappeared in both after a period of initial
      lag in presence of endosulfan. The duration of lag increased with increasing
      doses of pesticide. Paradoxically, however, the rate of uptake of NO3-, NO2- and
      NH4+, pigment and glycogen content progressively increased with increasing doses.
      The difference in the adaptation response between wild and mutant types was
      observed only in the concentration of pesticide that could be tolerated; with the
      mutant tolerating 2.5 fold more.

PMID- 8292272
TI  - Determination of acrylamide metabolite, mercapturic acid by high performance
      liquid chromatography.
AB  - A HPLC Assay was developed to identify and measure the metabolite of acrylamide,
      mercapturic acid, N-Acetyl-s-(propionamide)-cysteine (APC) in urine. O
      phthalaldehyde (OPA) was utilized as a precolumn derivatizing agent in the assay.
      This derivative was isolated with a good selectivity by high performance liquid
      chromatography (HPLC) employing reversed phase ODS columns. The quantitation of
      the mercapturic acid derivative was reproducible and with a detection limit of 1
      pmol. The average coefficient of variation for the runs carried out on the same
      day was approximately 4.6% at the range of 80-160 mumol.L-1 of APC, and the mean
      analytical recovery from urine samples was 94%. The metabolite of urine of
      workers exposed to acrylamide was identified as N-acetyl-s-(propionamide)
      cysteine by HPLC chromatography and fluorescence scan and HPLC-Mass spectra. All
      results were identical with the authentic synthesized compound.

PMID- 8292273
TI  - Relation of IL-2, IL-3 and IL-4 with allergic asthma induced by spores of
      mushroom (Pleurotus sapidus).
AB  - The effects of IL-2, IL-3, and IL-4 activities on occurrence of allergic asthma
      induced by spores of mushroom have been studied by measuring the IL-2, IL-3, and
      IL-4 activities in culture supernatants of spleen lymphocytes from guinea pigs
      being stimulated with Con A. The IL-4 activity (14.9 +/- 0.18 u) in the culture
      supernatant was higher than control group (6.7 +/- 1.5 u). The IL-2 and IL-3
      activities were all similar to that of the control group. The IL-4 synthesis was
      similarly raised as the IL-4 activity. These results indicated that there is a
      relationship between the occurrence of allergic asthma and the increase of IL-4.

PMID- 8292274
TI  - A review on molecular physiology of malate and lactate dehydrogenases in fishes.

PMID- 8292275
TI  - Preliminary study on aluminum content of foods and aluminum intake of residents
      in Tianjin.
AB  - Aluminum contents of 64 kinds mof foods in Tianjin were determined. The results
      showed that the aluminum levels in different kinds of foods varied greatly, and
      most foodstuffs from natural sources (including contamination from food
      processing) contained less than 10 mg/kg. Aluminum contents were higher in
      foodstuffs of plant origin, especially dry beans containing large amounts of
      aluminum naturally. Lower concentration of aluminum seemed to be present in
      foodstuffs of animal origin. It was estimated that the potential daily intake of
      aluminum per person from natural dietary sources in Tianjin was about 3.79 mg.
      This estimated figure of dietary aluminum intake was very close to the measured
      data from 24 daily diets of college students, which was 4.86 +/- 1.72 mg.
      Considering all the potential sources of natural aluminum in foods, water and the
      individual habitual food, it would appear that most residents in Tianjin would
      consume 3-10 mg aluminum daily from natural dietary sources.

PMID- 8292276
TI  - Concordance between observers in descriptions of personality change in
      Alzheimer's disease.
AB  - To evaluate observer bias and to estimate observer concordance for descriptions
      of personality changes in dementia, the authors examined the personality
      descriptions of dementia patients provided by 2 informants. Twenty-two patients
      with Alzheimer's disease were rated on the NEO-PI by each of 2 informants, the
      primary caregiver and another relative or friend. Each informant completed the
      NEO-PI to describe current behavior and premorbid behavior. Significant
      differences between premorbid and current descriptions were found for 4 of the 5
      personality dimensions measured. There was substantial agreement between
      independent raters, as indicated by significant correlations between raters for 4
      dimensions and the absence of significant differences between rater averages.
      These results suggest that both primary caregivers and others who know a patient
      well may serve as informants for studies of personality in dementia.

PMID- 8292277
TI  - Typography manipulations can affect priming of word stem completion in older and
      younger adults.
AB  - The experiments reported here investigated whether changes of typography affected
      priming of word stem completion performance in older and younger adults. Across
      all experiments, the typeface in which a word appeared at presentation either did
      or did not match that of its 3-letter stem at test. In Experiment 1, no
      significant evidence of a typography effect was found when words were presented
      with a sentence judgment or letter judgment task. However, subsequent experiments
      revealed that, in both older and younger adults, only words presented with a
      syllable judgment task gave rise to the typography effect (Experiments 2-4).
      Specifically, performance was greater, when the presentation and test typeface
      matched than when they did not. Experiment 5, which used stem-cued recall, did
      not reveal a difference between syllable and letter judgment tasks. These
      findings highlight the complex nature of word stem completion performance.

PMID- 8292278
TI  - Age-related slowing and the time course of semantic priming in visual word
      identification.
AB  - In 4 experiments, the authors investigated the time course of semantic priming
      effects during 2 forms of visual word identification, lexical decision and
      pronunciation. On each trial, a target letter string was preceded by a single
      word priming context. The effects of varying the stimulus onset asynchrony
      between the prime and the target indicated that the time course of semantic
      priming was equivalent for young and older adults. There were no consistent
      differences between lexical decision and pronunciation in the time course of
      semantic priming. The age differences associated with response selection were
      greater than would be predicted by generalized age-related slowing. The semantic
      priming effects were also inconsistent with a generalized slowing model, but the
      reliability of these effects was substantially lower than the reliability of the
      other task-related variables.

PMID- 8292279
TI  - Linking retirement experiences and marital satisfaction: a mediational model.
AB  - The authors propose and test a mediational model linking the experience of
      retirement with marital satisfaction. The experience of retirement (financial
      strain, time structure, a sense of purposefulness, and interpersonal contacts) is
      held to predict marital satisfaction indirectly through its sequential effects on
      context-specific well-being (retirement-specific satisfaction with health,
      activities, and peers) and context-free well-being (depressive symptoms). Both
      this model and a revised model in which retirement satisfaction also exerted a
      direct effect on marital satisfaction were supported using structural equation
      modeling on data from 164 retirees (mean age = 69 years). An alternative model in
      which depressive symptoms assume a predictive rather than mediational role was
      not supported; cross-lagged regression analyses excluded the possibility that
      marital dissatisfaction resulted in depressive symptoms. The conceptual and
      practical implications of these findings are discussed.

PMID- 8292280
TI  - Individual difference and contextual variables influence spatial memory in
      younger and older adults.
AB  - This study examined the influence of individual difference and contextual
      variables on the magnitude of age differences in memory for spatial location.
      Younger adults and 2 samples of older adults that differed in educational
      attainment, verbal intelligence, and working memory ability were compared. Ss
      studied and later recreated an arrangement of small objects that were placed on a
      plain map or a visually distinctive model. The objects were either unrelated or
      categorically related items. The results indicated that distinctive context
      enhanced spatial memory, and the magnitude of the benefit was generally
      comparable across age groups and stimulus sets. Hierarchical regression analyses
      confirmed that working memory resources accounted for a sizable proportion of age
      related variance in memory for spatial location. The implications of these
      results for current views on age-related differences in memory for spatial
      location are discussed.

PMID- 8292281
TI  - The origins of individual differences in memory among the elderly: a behavior
      genetic analysis.
AB  - The purpose of this investigation was to apply behavior genetic methods to
      investigate individual differences in memory performance. Memory and various
      cognitive and lifestyle variables were obtained from 93 monozygotic twin pairs
      and 67 dizygotic twin pairs aged 60-88 years as part of the Minnesota Twin Study
      of Adult Development and Aging. Univariate analysis, used to determine the
      relative influence of genetic and environmental factors on 4 measures of memory
      (word recall, immediate and delayed text recall, and figure memory), suggested
      that 55% of the variance in memory performance could be attributed to genetic
      factors. Bivariate analysis was used to determine the specific variables that
      mediate the genetic and environmental influences on memory. Results suggested
      that the relationship between memory and cognitive variables was genetic in
      nature, whereas the nature of the relationship between memory and lifestyle
      variables was environmental.

PMID- 8292282
TI  - Aging and prose memory: tests of the resource-deficit hypothesis.
AB  - Two experiments tested predictions that age differences in processing resources
      underlie age differences in prose recall. Topic familiarity, text length, and
      speed of text presentation were manipulated and reduced the amount recalled in a
      manner consistent with the hypothesis that these variables would tax processing
      resources. The amount of information recalled was systematically lower in older
      adults, but age differences were not increased by the experimental manipulations
      as expected. However, measures of the putative processing resources did account
      for some of the age-related variance in prose recall, and relative memorability
      functions suggested that the experimental manipulations interfered with the
      quality of recall in older adults more than in younger adults. The outcome did
      not support the resource-deficit hypothesis as originally proposed and may best
      be understood in terms of factors other than age-related deficits in the measured
      amounts of processing resources.

PMID- 8292283
TI  - Self-reported hearing problems in daily life throughout adulthood.
AB  - The authors assessed age differences on self-reported hearing problems on the
      performance of auditory tasks in the natural environment. The Your Hearing
      questionnaire was administered to 265 respondents (aged 20-94 years). Both the
      degree and variability of self-reported hearing problems were found to increase
      significantly with age, including those associated with listening to speech under
      conditions of background noise, the perception of normal and distorted speech,
      and the perception of short segments of speech and the perception of high-pitched
      sounds. Experienced hearing problems were greater for Ss who judged their hearing
      as being of poor quality. Findings suggest that self-report measures can provide
      valuable insights into the impact of age-related hearing disability on daily life
      that are not provided by more traditional laboratory-based studies.

PMID- 8292284
TI  - Primary aging, secondary aging, and intelligence.
AB  - The distinction between primary aging, representing innate maturational
      processes, and secondary aging, representing the effects of environment and
      disease (Busse, 1969), was used to develop a model for the assessment of factors
      that are associated with age-related individual differences in intelligence.
      Intelligence was measured by performance on a number of tests that measure
      cognitive abilities known to decline with age. In a hierarchical multiple
      regression analysis, primary aging and education but not health explained a
      significant portion of the variance in fluid intelligence. Chronological age had
      a residual effect over and above that of primary and secondary aging, indicating
      that there was remaining age-associated variance unaccounted for in the proposed
      model. The results suggest that the model of primary and secondary aging is a
      valid means of operationalizing chronological age.

PMID- 8292285
TI  - Concomitant eyeblink and heart rate classical conditioning in young, middle-aged,
      and elderly human subjects.
AB  - Pavlovian heart rate (HR) and eyeblink (EB) conditioning were assessed in 4
      groups of Ss who differed in age: young = 19-33 years, young middle-aged = 35-48
      years, old middle-aged = 50-63 years, and old = 66-78 years. A 100-ms corneal
      airpuff was the unconditioned stimulus and a 600-ms tone was the conditioned
      stimulus. A nonassociative control group received explicitly unpaired tone and
      airpuff presentations. All Ss were studied for 2 100-trial sessions separated by
      approximately 7 days. An impairment in acquisition of both the EB and HR
      responses occurred in the old and middle-age Ss, but all age groups showed
      significantly greater conditioning than did the control group. Slight increases
      in performance resulted from a 2nd session of training. These findings suggest an
      age-related impairment in a general associative process.

PMID- 8292286
TI  - Semantic activation and episodic odor recognition in young and older adults.
AB  - Young, young-old, and old adults were examined in immediate and delayed episodic
      recognition of common odors. Items were presented in 3 different formats: name
      only, odor-only, or odor-name. Ss made familiarity ratings for all items at
      study. In the delayed recognition test, Ss were asked to name the odors. Young Ss
      outperformed the 2 older age groups in both recognition tests, although the 2
      older groups did not differ. Performance was higher in the odor-name condition
      than in the single-format conditions. Both familiarity and naming were related to
      recognition in all age groups. Most important, when naming was statistically
      controlled, age differences in odor recognition disappeared, suggesting that
      access to verbal labels largely determine age differences in recognition of
      common odors. Finally, the finding that recognition was enhanced in both young
      and older Ss in the odor-name condition suggests that odor memory may involve a
      similar degree of plasticity as other varieties of episodic memory.

PMID- 8292288
TI  - Adults' conceptions of everyday memory failures in others: factors that mediate
      the effects of target age.
AB  - This study investigated young and older adults' conceptions of memory failure in
      others. One hundred young and 100 older adults rated memory failures in targets
      of 20, 40, 60, and 80 years of age as to how likely the memory failures were due
      to lack of effort or lack of ability. With increasing age, targets' forgetful
      episodes were rated as less likely to be caused by lack of effort and more likely
      to be due to lack of ability. A Subject Age x Target Age interaction on ability
      ratings showed age to be more salient for older subjects. Memory content, type of
      memory, subject sex, and target sex all influenced judgment of memory failure.
      The results support Erber's (1989) notion of a double standard in memory-failure
      appraisal; they demonstrated that adults' conceptions of memory include a
      decremental view of memorial ability with increasing age that is differentially
      sensitive to subject, target, and memorial variables.

PMID- 8292287
TI  - Evidence for identity inhibition during selective attention in old adults.
AB  - Previous studies of negative priming have shown that, relative to young adults,
      old adults can effectively suppress location information associated with stimuli,
      but not information about the identity of stimuli. S.L. Connelly and L. Hasher
      (1993) attributed this dissociation to an age-related decrement in the inhibitory
      processes that suppress meaning-bearing information. In this study, the authors
      report both identity negative priming and distractor interference in a group of
      young and old adults. Their results force a reconsideration of an age-related
      decrement in the inhibitory processes underlying the suppression of meaning
      bearing information. The results also suggest that whether a relationship between
      negative priming and interference is observed may depend on whether the 2
      measures index the same level of processing.

PMID- 8292289
TI  - Age differences in the psychological consequences of Hurricane Hugo.
AB  - At 12, 18, and 24 months after Hurricane Hugo, 831 adults were interviewed
      regarding their disaster-related stressors and present psychological state. The
      study's purposes were to assess whether age influenced one's vulnerability to
      postdisaster stress and to evaluate four different perspectives on disaster
      recovery that have been previously used to explain age differences. Regression
      analyses demonstrated that disaster exposure had substantial and pervasive
      psychological effects. The analyses also revealed a curvilinear interaction
      between disaster exposure and age. Younger people exhibited the most distress in
      the absence of disaster, but middle-aged people did so in its presence.
      Differential exposure, resources, and inoculation all failed to explain these
      differences, however, the burden perspective had considerable explanatory power.

PMID- 8292290
TI  - Effects of aging on planning and implementing arm movements.
AB  - In Experiments 1 and 2, aiming movements were performed with and without visual
      feedback in young and elderly adults. The initial (acceleration and deceleration
      phases) and secondary movement components were analyzed. Although deceleration
      phase accuracy decreased without visual feedback in both age groups, accuracy
      diminished as movement amplitude increased only in the elderly. This suggested
      that the elderly were more dependent on visual feedback to modify motor programs
      for longer duration movements. Velocity also increased less with increasing
      amplitude and target size in the elderly, which was related to impaired
      preprogramming (acceleration phase) and implementation (deceleration phase) of
      higher forces. This conclusion was confirmed directly in Experiment 2 because
      only the deceleration phase was affected by the removal of visual feedback of arm
      position when availability of visual information could not be predicted before
      movement.

PMID- 8292291
TI  - [Criteria for culpability of substance dependent patients in various types of
      crime].
AB  - When judging whether a person is capable of committing a punishable offense in
      connection with effects of drugs we have to differentiate between an addict and
      an occasional consumer of drugs. In last case we can orientate ourselves only by
      the commonly visible signs of the drug-effect found with such persons. Contrary
      to this is drug-addiction an illness influencing the total mind of a person to
      act in a certain way. This leads to a typical behavioral pattern whereby the
      addict, whilst trying to procure his drug, mostly shows also limitations of his
      ability to act responsible in accordance with the law section 21 StGB. "Normal"
      punishable offences of drug-addicts are to be judged by the performance and the
      behaviour of the person.

PMID- 8292292
TI  - [Empirical studies of automobile driving fitness of patients treated with
      methadone-substitution].
AB  - The aim of this experimental study was to gain an impression on the driver
      fitness of heroin addicts which were at the moment substituted by methadone
      especially within a methadone program sponsored by the government of NRW. 21 out
      of 34 patients investigated were unfit to drive because they were at the time the
      tests were conducted under the effect of at least one additional psychotropic
      substance other than methadone or because at prior blood tests within 3 months
      they had been found at least twice under the effect of psychotropic drugs or they
      were known as concomitant drug users. The remaining 13 methadone patients were
      matched with 13 control subjects of the same sex, education and-within a range of
      +/- 2 years-also the same age. Testing short term memory, tracking, decision and
      reaction behavior, perception, sustained attention, speed estimation, peripheral
      attention with simultaneous central task, reactive loading, personality
      questionnaires including traffic specific questions and psychopathologic
      characteristics the patients yielded significant poorer results compared with the
      control group. When selecting 6 very good patients according to the decision of
      the physicians the significant differences concerning performance measures
      vanished but some differences concerning personality traits still remained. The
      results confirm the expert's opinion-called "disease and motor traffic"-that in
      general methadone substituted patients are unfit to drive. The driver fitness of
      the very few optimal patients depends on the amount of the personality disorders.

PMID- 8292293
TI  - [Rate of ethanol clearance after oral and parenteral ethanol administration].
AB  - A crossover investigation of the ethanol concentration decline after oral and
      parenteral administration of ethanol respectively was performed with direct intra
      and interindividual comparison. No significant differences in relation to the
      kind of administration were noted. An influence of the circadian rhythm on the
      rate of decline could be excluded. The low beta 60 values derived (average: 0.111
      g/kg/h) can be explained by the long period over which the probands were denied
      food.

PMID- 8292294
TI  - [Proof of alcoholic intoxication in automobile driving by breath alcohol content
      in Austria from the legal viewpoint].
AB  - In Austria, automobile drivers are obligated to undergo a breathalizer test if
      they are suspected of driving under the influence of alcohol. Drivers cannot be
      forced to take the test, but if they refuse, their conduct is then dealt with as
      a violation of civil law and is therefore punishable by law. If the Alcomat test
      yields an alcohol content of 0.4 ml/l, i.e. relevant amount, the suspect then has
      the right to demand that a blood test be carried out. If the authorities refuse
      to give him this test, then the suspect will not be held to have been in excess
      of the legal alcohol level by the civil authorities in the following proceedings.
      On the other hand, in a legal criminal proceeding, the suspect will then be found
      guilty of exceeding the legal alcohol level, if additional evidence--which must
      be examined by the judge within the framework of the free consideration of
      evidence (a principle recognized by Austrian law but not, for example, by
      American law)--suffices to show with relative certainty that the suspect exceeded
      the alcohol limit as defined in section 81 Z2StGB). If a blood test is completed
      and the results differ from those of the breathalizer, then the blood test
      results are used.

PMID- 8292295
TI  - [A large undertaking. The campaign against alcohol offenses in the USA].

PMID- 8292296
TI  - Cardiac natriuretic peptides in heart failure.

PMID- 8292297
TI  - Bioethics in Europe.

PMID- 8292299
TI  - Dental caries, sugars and xylitol.

PMID- 8292298
TI  - Activation of dermal connective tissue in scleroderma.
AB  - Systemic scleroderma is an acquired disorder which typically results in fibrosis
      of the skin and internal organs. The pathogenesis of systemic scleroderma is
      characterized by three distinct processes: microvascular alterations including
      capillary endothelial cell injury, perivascular inflammatory reaction in dermis,
      and excessive accumulation of collagen in the dermal layer of lesional skin. In
      this review, molecular mechanisms resulting in activation of collagen synthesis
      by dermal fibroblasts in scleroderma are discussed. Specifically, the role of
      inflammatory cells and the cytokines/growth factors produced by these cells in
      the pathogenesis of scleroderma is emphasized. The possibilities for prevention
      and resolution of tissue fibrosis on the basis of these observations are also
      discussed. Understanding the pathogenetic mechanisms of scleroderma at a
      molecular level is likely to provide possibilities for development of more
      specific therapeutic modalities for this and other fibrotic disorders.

PMID- 8292300
TI  - Prosthetic osteomyelitis with special reference to the knee: risks, treatment and
      costs.
AB  - The overall incidence of osteomyelitis following primary knee arthroplasty is 1
      2%. Major risk factors are large prostheses, rheumatoid arthritis, postoperative
      wound-healing complications, skin infections, and prior deep infections. The
      major infecting organism is Staphylococcus aureus. Healing of the infection is to
      be expected in 20% when systemic antibiotics alone are used, in 24% when soft
      tissue surgery is used, in 50% when resection arthroplasty is used, in 76% when
      revision arthroplasty is used, in 90% when arthrodesis is used, and in 100% when
      amputation is used. The direct medical costs average US$ 62,100 for an infected
      patient and US$ 8600 for a non-infected patient. Attention should focus on
      prophylactic measures directed towards the soft tissue problems: by avoiding
      conflicting skin incisions, by gentle handling of the periarticular soft tissues,
      by avoiding the use of constrained prostheses and oversized compartmental
      prostheses, by letting wound healing take priority over motion in knees with
      compromised soft tissues, and by using prophylactic antibiotic treatment for skin
      ulcers until these have healed.

PMID- 8292301
TI  - The male climacterium.
AB  - In contrast to women, fertility in men persists until a very old age. However,
      testicular function of both the exo- and endocrine compartments decreases in old
      age, causing a series of clinical symptoms which are analogous to, although less
      pronounced than, the menopausal syndrome. These symptoms can be considered to
      represent the male climacterium or andropause. However, whereas at menopause
      ovarian hormonal secretion ceases almost completely, the decrease in the levels
      of biologically active endrogens (free testosterone) is only moderate and many
      elderly men have free androgen levels that would be considered normal for young
      men. Moreover, whereas many well-controlled studies have shown the benefit of
      hormonal replacement therapy, at least for symptomatic posmenopausal women, so
      far no well-controlled studies exist that prove a favourable risk/benefit balance
      of androgen substitution in elderly men. The major risk is the potentially
      stimulating effect of androgens in elderly men who frequently present with
      subclinical prostatic carcinoma. Therefore, the generalized use of androgen
      substitution in elderly men cannot, as yet, be recommended.

PMID- 8292302
TI  - Growth factors: therapeutic advances in wound healing.
AB  - Polypeptide growth factors regulate cellular processes involved in wound healing.
      Application of exogenous growth factors can modify the healing process and, with
      recombinant DNA technology, growth factors can now be made in sufficient quantity
      to be used therapeutically. Several growth factors are showing promising results
      in clinical trials, especially in cases of impaired healing, such as chronic
      ulcers. Preclinical studies indicate that further growth factors may have
      therapeutic potential in a wide range of wound-healing applications. The use of
      specifically designed and modified growth factors, growth-factor inhibitors, and
      sequential and combinatorial dosing regimes offer further possibilities for
      enhancing wound healing.

PMID- 8292303
TI  - Apolipoprotein B mRNA editing: a key controlling element targeting fats to proper
      tissue.
AB  - Apolipoprotein B (apo B) circulates in two distinct forms referred to as apo B100
      and apo B48. Apo B48 is colinear with the amino-terminal half of apo B100 and
      arises as a result of a post-transcriptional modification, termed apo B mRNA
      editing. This process changes a single cytidine nucleotide in apo B100 mRNA
      thereby altering a CAA codon, encoding glutamine in apo B100, to a UAA codon,
      which specifies an in-frame stop codon in apo B48. The functional consequences of
      apo B mRNA editing include the divergent catabolism of plasma lipoproteins
      expressing either apo B100 or B48, and also the ability to generate the hybrid
      lipoprotein, Lp(a). These differences arise because the requisite regions of apo
      B for interaction either with the low-density lipoprotein receptor or with
      apolipoprotein (a) are contained within the carboxyl terminus of apo B100. Apo B
      mRNA editing is regulated by species, tissue and cell-specific factors, one of
      which has been recently cloned. The further characterization of apo B mRNA
      editing, the first example of a mammalian gene regulated by post-transcriptional
      nucleotide alteration, will be important for an understanding of lipoprotein
      assembly.

PMID- 8292304
TI  - Acute haematogenous osteomyelitis in children in Finland. Finnish Study Group.
AB  - The purpose of the study was to evaluate the history, clinical picture and
      diagnostic difficulties of acute haematogenous osteomyelitis (AHOM) in children.
      Forty-seven children under the age of 15 with bacteriologically proven AHOM were
      collected prospectively in Finland in 1981-93. Staphylococcus aureus was
      responsible for 89% of the cases. The commonest sites affected were the tibia
      (25%) and the femur (23%) followed by the pelvis (15%) and the calcaneus (11%).
      Sites other than the long bones increased in frequency in children over the age
      of 4 years. Most of the children came with a history of a week or less with
      classic signs and symptoms of AHOM, increased C-reactive protein (CRP) and
      erythrocyte sedimentation rate (ESR) values but negative X-rays. Delay in
      hospital admission was observed in 19%. In 11% antimicrobial therapy was not
      instituted within 48 hours on ward. All children were clinically healthy at the 1
      year check-up with minor X-ray changes seen in 11 patients. We conclude that
      children in Finland seek treatment early in the course of AHOM and have a good
      outcome. S. aureus is the main aetiological agent affecting primarily the long
      bones, but in older children pelvic and calcaneic sites are also frequent. No
      significant delays affecting the outcome were noticed in admittance to hospital
      or in the diagnosis of AHOM.

PMID- 8292305
TI  - Autoantibodies against low-density lipoprotein and atherogenic potential of
      blood.
AB  - Blood serum of ischaemic heart disease patients possesses an atherogenic
      potential which manifests itself in the accumulation of cholesterol in cultured
      smooth muscle cells of human aorta and in mouse peritoneal macrophages. Recently
      it was found that serum atherogenicity is associated with the presence in the
      blood of modified (desialylated) low-density lipoprotein (LDL) and of
      autoantibodies against LDL (anti-LDL). In the blood, anti-LDL and LDL form
      circulating immune complexes (CIC). Blood serum atherogenic potential is directly
      related to the content of LDL cholesterol or apolipoprotein B in CIC. The present
      study elucidates the effect of LDL and anti-LDL concentrations on the atherogenic
      properties of blood serum. After the addition of exogenic LDL, in certain
      atherogenic sera a significant increase in CIC cholesterol as well as the
      increase of serum atherogenic potential revealed in cell culture were registered.
      In these sera free anti-LDL capable of binding to exogenous LDL were detected. In
      other atherogenic sera and in all non-atherogenic sera, the LDL increase failed
      to be accompanied by any changes in the CIC cholesterol. In these sera no free
      anti-LDL were detected. The addition of exogenous anti-LDL into non-atherogenic
      sera was accompanied by 2.5-fold increase in CIC cholesterol and by the
      appearance of atherogenic properties in these sera. Affinity chromatography was
      used to remove anti-LDL from atherogenic sera. This removal was accompanied by
      2.5- to 3-fold decrease in the CIC cholesterol up to the level characteristic of
      non-atherogenic serum of healthy donors. The removal of anti-LDL led to
      disappearance of serum atherogenic properties. From these data we assume that the
      CIC LDL level and, consequently, serum atherogenic potential is to a considerable
      degree determined by anti-LDL concentration in the serum.

PMID- 8292306
TI  - Viral association with Crohn's disease.
AB  - Crohn's disease is an inflammatory disorder of the gastrointestinal tract, the
      cause of which remains unknown. Since the first description by Dalziel in 1913
      (1), similarities between Crohn's disease and intestinal mycobacterial infection,
      particularly Johne's disease in ruminants, have been widely recognized (2, 3).
      After Mitchell and Rees demonstrated the transmission of granulomata from Crohn's
      disease by injecting intestinal homogenates into the footpads of mice (4), there
      followed many studies attempting to identify infective agents within the bowel of
      patients with Crohn's disease. Although Mycobacterium paratuberculosis has been
      identified in intestinal tissue from a proportion of patients with Crohn's
      disease, a convincing role for this agent in the aetiology of Crohn's disease has
      not been established (5). Likewise, extensive studies into bacterial (6-9) and
      viral (10) agents potentially associated with Crohn's disease have been
      inconclusive, although recent ultrastructural observations of viral particles
      within submucosal granulomata have added a new impetus to the search (11, 12).
      This review examines the evidence for an association between Crohn's disease and
      viral infection from epidemiological studies, transmission and cell culture,
      specific immunological responses, ultrastructure and from molecular biological
      techniques.

PMID- 8292307
TI  - Peptic ulcer: an infectious disease?
AB  - Since the ingestion studies by Marshall and Morris, Helicobacter pylori has been
      known to cause both acute and chronic infection in the human stomach activating
      both the cellular and the humoral immune system. It is of little or no value to
      evaluate the causative relationship of an infectious agent using Koch's criteria.
      The more recent criteria for causative relationships used in the science of
      epidemiology are more useful. These criteria include: (i) the characteristic of
      the association which is fulfilled for most cases of both duodenal and gastric
      ulcer; (ii) the temporal relationship which is fulfilled for duodenal ulcer and
      has not been investigated for gastric ulcer; (iii) the biological gradient which
      has been fulfilled for duodenal ulcer in a few studies but not investigated for
      gastric ulcer; (iv) the biological plausibility which is easily fulfilled for
      both duodenal and gastric ulcer; (v) the effect of an intervention which has been
      fulfilled for duodenal ulcer and in a few studies for gastric ulcer; and (vi) the
      coherence of these data with what is known about the disease which is fulfilled
      for both duodenal and gastric ulcer. Even though there is no need for all
      criteria to be fulfilled, further studies are necessary to confirm the temporal
      relationship between H. pylori and peptic ulcer, and the biological gradient of
      H. pylori in relation to the gastric ulcer. Even so, there is a strong indication
      that most of the peptic ulcers, apart from those caused by non-steroid anti
      inflammatory drugs and Zollinger-Ellison-like syndromes, are caused by H. pylori
      infection.

PMID- 8292309
TI  - Conceptual and psychometric concerns about the 1992 AAMR definition of mental
      retardation.
AB  - The new American Association on Mental Retardation (AAMR) definition of mental
      retardation (Luckasson et al., 1992) represents a radical departure from previous
      definitions. In the present paper we examined the extent to which the new
      definition provides decision rules to guide clinicians and researchers in
      classification efforts. We concluded that the IQ criterion of 75 will increase
      the proportion of the general population eligible near the cut-off score.
      Moreover, the 10 adaptive skill areas adopted fail to consider developmental
      factors and cannot be assessed reliably with current scales. Proposed
      differentiation by levels of needed supports is also challenged as being
      imprecise and not amenable to reliable measurement. Implications of this new
      definition for diagnostic practices and research endeavors were explored.

PMID- 8292308
TI  - Is juvenile diabetes a viral disease?
AB  - The purpose of this review is to discuss recent literature data concerning the
      etiology and pathobiology in insulin-dependent diabetes mellitus as well as
      present our own experience from all children up to 15 years of age in Uppsala
      County, Sweden presenting with juvenile (type I) diabetes since 1976. Chronic
      enterovirosis is an emerging concept in apparently immunologically competent
      patients. By means of new serological and DNA-based methods, a persistent
      enteroviral (Coxsackie virus A, B and ECHO virus) infection can sometimes be
      demonstrated after an acute primary infection, which is often subclinical. There
      are several indications that these viruses can contribute to the development of
      illnesses with a pathogenesis as yet not fully understood, e.g. dilated
      cardiomyopathy, type I diabetes, and possibly some cases of the so-called chronic
      fatigue syndrome. In type I diabetes, many pieces of evidence including
      epidemiology, genetic analysis of the host susceptibility genes, cytokine
      analysis and new seriological evaluation suggest an infection to be the starting
      point for the beta cell destruction. These etiological agents most likely belong
      to the enteroviral group of picornaviruses. Later events may well involve all
      parts of the immune system launching a selective autoimmune 'suicidal attack' on
      the cells necessary for glucose homeostasis.

PMID- 8292310
TI  - Similarities in the detection of stimulus symmetry by individuals with and
      without mental retardation.
AB  - Intelligence-related differences in the detection of stimulus organization
      previously identified by Soraci, Carlin, Deckner, and Baumeister (1990) were
      examined further to determine whether they would (a) extend to similar
      checkerboard stimuli varying solely with respect to symmetry and (b) generalize
      to form-like polygon stimuli. Detection performances of 10 individuals with mild
      mental retardation, 10 CA-matched, and 10 MA-matched individuals were assessed on
      a rapid presentation a two-choice match-to-sample task. The organizations of the
      target and distractor stimuli were varied across four levels of symmetry: double,
      vertical, horizontal, and asymmetrical. Results indicated that detection rates
      for each group were highest when the target stimulus was vertically symmetrical
      or when target-distractor structural disparity was maximal. However, no
      significant main effects of subject group or stimulus type (i.e., checkerboard
      vs. polygon) were found, thereby arguing for the robustness of the symmetry
      effect across groups differing in intelligence and physically dissimilar stimulus
      types.

PMID- 8292311
TI  - Using stable isotopes to assess reduced physical activity of individuals with
      Prader-Willi syndrome.
AB  - The contribution of reduced levels of physical activity to the positive energy
      balance found in most individuals with Prader-Willi syndrome is not known. We
      assessed total energy expenditure using stable isotopes and resting energy
      expenditure using open circuit indirect calorimetry in a group of 10 children
      with this syndrome. The difference between these two measures is primarily the
      energy cost of activity and is often called a physical activity level. After
      adjusting for age, we found that the physical activity level values of these
      children were significantly reduced in comparison to children who did not have
      Prader-Willi syndrome. Increasing activity levels in children with Prader-Willi
      syndrome will raise total energy expenditure and may help to control their
      development of weight gain.

PMID- 8292312
TI  - Diagnosis and fluoxetine treatment of compulsive behavior disorder of adults with
      mental retardation.
AB  - A set of research diagnostic criteria was developed to identify potential
      obsessive-compulsive disorders among individuals with mental retardation and
      aberrant behaviors. The behavior disorders of 10 subjects who met criteria for
      compulsive behavior disorder and 6 subjects who did not (comparison subjects)
      were treated using the medication fluoxetine. All subjects were evaluated using
      an A-B open-trial method with 4-month baseline and treatment phases. Seven of the
      10 subjects with compulsive behavior disorder responded favorably to fluoxetine
      treatment; none of the comparison subjects responded favorably to this
      medication. Further, there appeared to be a relation between manifest motor
      stereotypies, compulsive behaviors, and response to fluoxetine.

PMID- 8292313
TI  - Out-of-home placement for children with mental retardation: dimensions of family
      involvement.
AB  - The involvement of families with a child who has mental retardation in
      residential placement was studied. Sixty-two families who had placed their child
      out of the home within the previous 2 years were interviewed about behavioral and
      emotional aspects of involvement. Involvement was high, with 81% of families
      having at least a monthly visit with their child. There was only marginal
      evidence for detachment, a lessening of involvement over these 2 years. Although
      family involvement related to several child and family characteristics, the
      strongest relation was with facility characteristics, especially opportunities
      for involvement in the facility.

PMID- 8292314
TI  - Influence of social partner on interactions of toddlers with disabilities:
      comparison of interactions with mothers and familiar playmates.
AB  - The social exchanges of young children with developmental disabilities over time
      with two different social partners and the nature of these exchanges were
      compared. Thirty-three toddlers with developmental disabilities were video-taped
      for 15 minutes with each partner at two different data points. Data were
      transcribed and coded using a modification of Vandell and Wilson's (1979) coding
      system. Results showed that more of the observation time was spent socially with
      mothers than with peers, and the number of turns per exchange was longer with
      mothers. In contrast, toddlers initiated more social exchanges with peers than
      with mothers. There were similarities in the content of the social exchanges with
      both partners. There were few changes over time, although exchanges consisted of
      more purely social behaviors at Time 2. Results were interpreted with respect to
      implications for early intervention.

PMID- 8292315
TI  - Personal competencies and community participation in small community residential
      programs: a multiple discriminant analysis.
AB  - We examined whether broad factors assessing dimensions of personal competency and
      community participation could be used to discriminate between people with mental
      retardation who were living in small group homes and small foster homes. Using a
      large national sample and multiple discriminant analysis procedures, we found
      that personal competencies were least important in distinguishing on the basis of
      setting between people living in the two types of residential placements. Primary
      differences emerged in factors assessing extent of community participation,
      family relationships, and recreation/leisure integration. Implications for policy
      and future research were presented and discussed.

PMID- 8292316
TI  - Placement from a community-based mental retardation program: a 15-year follow-up.
AB  - The current status of 85 persons placed into independent housing and competitive
      employment 15 years ago was evaluated. Two primary groups emerged: those in and
      those not in MR/DD services (19% and 59% of sample, respectively). Personal
      interview and observational data were used to evaluate the person's life (e.g.,
      social and support networks, life style and role functions, activity patterns,
      measured quality of life, and expressed satisfaction). The two groups were
      compared on these data sets as well as on previously obtained behavioral skill
      data and family support levels. Implications of the study were discussed in
      reference to natural and long-term support needs, the recent paradigm shift in
      habilitation and evaluation strategies, and the ongoing concern about quality of
      life of individuals with disabilities.

PMID- 8292317
TI  - Affective symptoms of institutionalized adults with mental retardation.
AB  - A survey of affective symptoms in two groups of institutionalized adults with
      mental retardation was conducted. The groups were comprised of subjects with
      prior diagnoses of affective disorders or other psychiatric disorders. Informants
      reported retrospectively on the presence or absence of DSM-III-R criteria for
      major depression and mania. Thirteen percent of the affective disorders group did
      not meet these criteria for depression or mania, whereas 20% of the other
      psychiatric disorders group did. Aggression was a frequent concomitant of
      psychopathology in both groups. These findings support previous reports that
      affective disorders may be underdiagnosed in this population. However, unlike
      prior investigations, most of the subjects (74%) in the present survey had severe
      to profound mental retardation.

PMID- 8292318
TI  - Aging family caregivers: support resources and changes in burden and placement
      desire.
AB  - Determinants of older parents' caregiving burden and desire for residential
      placement of their adult child (over age 30) over a 2.5-year period were
      examined. The major focus was on the effects of informal and formal resources
      over time. Interviews were conducted with 62 parents. Regression analyses
      indicated that support resources contributed to parental caregiving burden and to
      residential placement preferences for their adult child. Implications for family
      support policies were discussed.

PMID- 8292319
TI  - Development of a theory of mind in individuals with mental retardation.
AB  - The ability of adolescents with mental retardation to reason about other people's
      mental states was examined. Subjects were asked questions about the knowledge and
      beliefs of characters in stories that they heard and saw enacted with props. The
      adolescents with mental retardation performed worse than did children without
      mental retardation matched for MA. The adolescents with mental retardation did
      better on questions requiring first-order reasoning than on those involving
      second-order reasoning; this pattern is similar to that found previously for
      children without mental retardation.

PMID- 8292320
TI  - Acute psychiatric hospital admissions of adults and elderly adults with mental
      retardation.
AB  - Records of 247 inpatients with mental retardation or autism discharged from a
      university hospital during 62 consecutive months were examined with regard to
      acute inpatient treatment. The main finding was that elderly adults with mental
      retardation had significantly more medical problems than did adults. There was a
      trend toward significantly more elderly adults being transferred to a state
      hospital. An unexpected finding was that the most common diagnosis in both adults
      and elderly adults was chronic schizophrenia, paranoid type. Limitations of the
      study and possible explanations of the findings were discussed.

PMID- 8292321
TI  - Spatial updating in Parkinson's disease.
AB  - We compared the ability of 48 patients with Parkinson's disease (PD) (24 mild, 24
      moderate) and 35 controls to remain oriented to the starting position after being
      transported passively in a wheelchair in two conditions: visual and vestibular.
      The moderate PD group demonstrated the poorest performance in both sensory
      conditions. The visual condition discriminated between the mild PD group and the
      controls, but both groups had similar performance in the vestibular condition.
      Poor performance of the PD group in the visual condition and controls in the
      vestibular condition correlated significantly with poor performance on selected
      balance tests. Poor performance in the visual condition correlated significantly
      with poor performance on judgment of line orientation in the mild PD group.
      Spatial updating, or maintaining a sense of orientation while being moved in the
      environment, may be impaired in PD and should be investigated as a possible
      contributing factor to problems with spatial orientation noted clinically in some
      patients.

PMID- 8292322
TI  - Hemisphere inactivation and mood-state changes.
AB  - Mood-state changes were studied during a sodium Amytal testing procedure in
      epilepsy patients with unilateral temporal lobe foci. The results showed that
      inactivation of the left hemisphere, but not the right hemisphere, produced a
      negative mood state. This decline in mood was not specifically related to side of
      focus or sex. As expected, the inactivation of either hemisphere also lead to an
      impairment in memory performance. This impairment was somewhat worse during a
      left than a right hemisphere inactivation. Furthermore, patients with left
      hemisphere foci showed a lower memory performance than patients with a right
      hemisphere lesion. These results suggest (a) a hemispheric specialization for
      emotion that underlie changes in mood and (b) a discrepancy between mood states
      at encoding (during inactivation) and retrieval (after inactivation).

PMID- 8292323
TI  - Reversed perceptual asymmetry for faces in left unilateral neglect.
AB  - Twelve patients with left unilateral neglect and 12 matched controls were
      examined on two tests of face perception. In the chimeric faces task, subjects
      were required to make a judgement of happiness on pairs of photographic chimeras,
      while in the face-matching task, they were required to indicate which of two
      symmetrical face composites more closely resembled the original. Whereas controls
      showed a significant leftward perceptual bias on both tasks, left neglect
      patients showed an even stronger rightward (reversed) perceptual bias. Patients
      with and without left-sided visual field defects exhibited the reversed
      asymmetry, and the degree of perceptual bias shown by patients was not related to
      the severity of their symptoms as measured by standard clinical tasks. There was
      no relationship between the extent of rightward bias exhibited by patients or
      controls on the two tasks. These results contribute to our understanding of the
      mechanisms underlying unilateral neglect. Moreover, the tasks themselves may be
      employed as a simple and sensitive adjunct to the clinical assessment of this
      disorder.

PMID- 8292324
TI  - Spatial and selective attention in the cerebral hemispheres in depression, mania,
      and schizophrenia.
AB  - Two tachistoscopic tests examining distinct aspects of attention were
      administered to normal subjects and patients with depression, mania, and
      schizophrenia. The first examined spatial attentional bias using happy-sad
      chimeric faces, known to elicit a perceptual bias to the left side of space in
      normal right-handers provided the right cerebral hemisphere is intact. The second
      used a lateralized version of the Stroop task, a traditional test of selective
      attention. Normals showed the expected leftward perceptual bias but showed
      equivalent susceptibility to the Stroop effect in both visual fields. As
      previously demonstrated with chimeric faces viewed in free vision, depression and
      mania were associated with weak and strong biases respectively with
      schizophrenics showing no bias to either side of space. The relationship between
      perceptual bias, as assessed by reaction time and absolute performance and the
      Stroop effect, showed differences according to diagnosis. This may be interpreted
      as evidence for the dissociability of attentional processes as well as
      lateralized differences in the pattern of cerebral activation in affective
      disorders and schizophrenia. The independence of performance variables on these
      tests in the schizophrenic group points to severe neuropsychological dysfunction.

PMID- 8292325
TI  - Praxis and the right hemisphere.
AB  - We report our observations on praxis in a strongly right-handed man following a
      massive stroke that resulted in virtually complete destruction of the left
      cerebral hemisphere. Our patient was severely impaired in pantomiming transitive
      gestures with the left hand and in reproducing novel non-symbolic hand and arm
      movement sequences. However, overlearned habitual actions like actual object use
      and intransitive gestures were relatively spared. Performance of axial commands
      was intact. Gesture recognition and discrimination were also preserved. Based on
      these findings, we propose that the praxis system of the right hemisphere is
      strongly biased toward "concrete" or context-dependent execution of familiar,
      well-established action routines. The right hemisphere is critically dependent on
      transcallosal contribution from the left hemisphere for control of the left hand
      in "abstract" or context-independent performance of transitive movements and in
      learning novel movement sequences. At least in some individuals, the right
      hemisphere can recognize and discriminate gestures. Possible implications of our
      findings for the cerebral control of praxis and for recovery from apraxia are
      discussed.

PMID- 8292326
TI  - Reduplication after right middle cerebral artery infarction.
AB  - Reduplication and misidentification syndromes are similar and peculiar phenomena
      of disorientation and beliefs with delusional qualities. They are more frequent
      among neurologic and psychiatric patients than previously thought. Organic
      factors play a definitive role in their occurrence. A case is presented which
      exemplifies reduplication of place and person, following a right hemisphere focal
      lesion. Current theories are briefly reviewed and possible roles of nortriptyline
      therapy and psychological factors are discussed in the pathogenesis of
      reduplicative phenomena in this patient.

PMID- 8292327
TI  - Components of random generation by normal subjects and patients with dysexecutive
      syndrome.
AB  - The study presents a hypothesis on how randomness could be simulated by human
      subjects. Three sources of deviation from randomness are predicted: (1) the
      preferred application of overlearned production schemata for producing sequences
      of digits, (2) a wrong concept of randomness, and (3) the impossibility to
      monitor for redundancies of higher- than those of first-order. Deviations of
      random generation of digits produced by healthy subjects, patients with chronic
      frontal lobe damage, and patients with Parkinson's disease from random sequences
      produced by a computer program can be explained by the differential influence of
      these factors. Whereas incorrect concepts of randomness and limits on monitoring
      capacity distinguished all sequences produced by humans from actual random
      sequences, persistence on a single production strategy distinguished brain
      damaged patients from controls. Random generation of digits appears to be a
      theoretically transparent and clinically useful test of executive function.

PMID- 8292328
TI  - Effects of responding hand and concurrent verbal processing on time-keeping and
      motor-implementation processes.
AB  - Two experiments examined the effects of concurrent verbal processing on the
      ability to tap at a consistent rate with the left and right index fingers.
      Variability in the intertap intervals was divided into two components that
      reflect different processes involved in such paced tapping. One component
      reflects the consistency of an internal time-keeping mechanism and the other
      component reflects the consistency of motor implementation. The imposition of a
      concurrent verbal processing task increased variability attributable to the
      internal time-keeping mechanism, but had no effect on variability attributable to
      motor implementation. Furthermore, the interference caused by concurrent verbal
      processing was equivalent for the two hands. Variability attributable to motor
      implementation was consistently smaller for the right than for the left hand and
      was not increased by imposing a concurrent verbal processing task. This pattern
      of results indicates that there is an important dissociation between time-keeping
      and motor-implementation mechanisms. Furthermore, the results suggest that a
      single time-keeping mechanism serves both index fingers and that the left
      hemisphere of neurologically intact right-handers plays an important role in the
      time-keeping circuit regardless of which hand is tapping.

PMID- 8292329
TI  - Hemispheric asymmetry in transient visual evoked potentials induced by the
      spatial factor of the stimulation.
AB  - In order to enhance the effect of spatial frequency on the hemispheric asymmetry
      of visual evoked potentials (VEP), the response amplitudes to ON-OFF modulated
      gratings were compared with the responses to pattern reversal stimulation.
      Sinusoidal gratings of different spatial frequencies were presented to six
      righthanders. VEPs were recorded from temporal leads on each hemisphere. In the
      left hemisphere, the amplitude was constant for the two modes of presentation and
      independent of spatial frequency. In the right hemisphere, the response amplitude
      was larger to the ONSET stage of ON-OFF stimulation than to reversal and
      presented the characteristic spatial frequency tuning curve. This asymmetry is
      assumed to reflect a difference in sensitivity of the two hemispheres to the
      spatiotemporal characteristics of the stimulus. The relevance of these findings
      is discussed in relation to the other hemispheric specialization models.

PMID- 8292330
TI  - A study of perceptual analysis in a high-level autistic subject with exceptional
      graphic abilities.
AB  - We report here the case study of a patient (E.C.) with an Asperger syndrome, or
      autism with quasinormal intelligence, who shows an outstanding ability for three
      dimensional drawing of inanimate objects (savant syndrome). An assessment of the
      subsystems proposed in recent models of object recognition evidenced intact
      perceptual analysis and identification. The initial (or primal sketch), viewer
      centered (or 2-1/2-D), or object-centered (3-D) representations and the
      recognition and name levels were functional. In contrast, E.C.'s pattern of
      performance in three different types of tasks converge to suggest an anomaly in
      the hierarchical organization of the local and global parts of a figure: a local
      interference effect in incongruent hierarchical visual stimuli, a deficit in
      relating local parts to global form information in impossible figures, and an
      absence of feature-grouping in graphic recall. The results are discussed in
      relation to normal visual perception and to current accounts of the savant
      syndrome in autism.

PMID- 8292331
TI  - Large-scale synthesis of triple helix forming oligonucleotides using a controlled
      pore glass support.
AB  - Triple helix forming oligonucleotides that involve purine:purine:pyrimidine
      interactions are purine-rich oligonucleotides containing 60%-90% G and are
      usually 25-40 bases long. Synthesis and purification of G-rich oligonucleotides
      of this length can be difficult even at small scales. Procedures to synthesize
      these compounds at 200 to 400 mumol scales with high coupling efficiency have
      been developed using a controlled-pore glass support.

PMID- 8292332
TI  - Spheroplast formation and plasmid isolation from Rhodococcus spp.
AB  - The genus Rhodococcus comprises aerobic gram-positive actinomycetes that show
      considerable morphological and metabolic diversity and are known to be involved
      in the development of plant diseases and degradation of environmental pollutants.
      We describe a method for cell lysis and large plasmid DNA isolation from
      Rhodococcus by creating lysozyme susceptible cells by predigestion with the
      enzyme mutanolysin. Mutanolysin action resulted in the liberation of reducing
      sugars and free amino acids from the peptidoglycan layers of the cell wall. A 1-h
      predigestion with mutanolysin followed by a 0.5-h incubation with lysozyme
      resulted in spheroplast formation. Complete lysis of cells and efficient
      isolation of intact large plasmid DNA (108 kb) from wild-type Rhodococcus strains
      was confirmed.

PMID- 8292333
TI  - Introduction of antisense oligonucleotides into cells by permeabilization with
      streptolysin O.
AB  - Cellular uptake of antisense oligonucleotides is critical to their ability to
      inhibit gene expression. In the present study, phosphodiester
      oligodeoxynucleotides were introduced into cells during brief permeabilization
      with the pore-forming agent streptolysin O. The extent of antisense inhibition
      was dependent on the concentration of oligonucleotide present during
      permeabilization. In addition, the level of antisense inhibition was time
      dependent; it reached a maximum at 18 h and subsequently diminished to control
      levels over the next 48 h. These results demonstrate the effectiveness of
      streptolysin O permeabilization as a means for simple and rapid introduction of
      oligonucleotides into eukaryotic cells.

PMID- 8292334
TI  - Permeabilizing millions of cells with single pulses of an excimer laser.
AB  - Poration of millions of cells with single laser pulses of an argon fluoride
      excimer laser is developed and demonstrated on plant cells. The essence of the
      technique is to use the large beam size (10 x 25 mm) of the excimer laser and to
      split it using an appropriate mask into millions of micron- or submicron-sized
      beams of 193-nm radiation with enough energy to perforate cell membranes and
      walls. The extremely small depth of penetration of the 193-nm radiation in
      biological tissue (< 1 microns) is used to great advantage in this technique to
      provide for a gentle method that does not lead to cell death. This is the first
      laser-based method that has enough throughput to make it viable for
      biotechnological applications. Of considerable significance is that the method is
      applicable not only in the case of the single cells in suspension, but also for
      cells growing on the leaves of living plants.

PMID- 8292335
TI  - Detection of the initial stages of DNA fragmentation in apoptosis.
AB  - DNA fragmentation during apoptosis proceeds through an ordered series of stages
      commencing with the production of DNA fragments of 300 kbp, which are then
      degraded to fragments of 50 kbp. The 50-kbp fragments are further degraded, in
      some but not all cells, to smaller fragments (10-40 kbp) and release the small
      oligonucleosome fragments that are recognized as the characteristic DNA ladder on
      conventional agarose gels. Methodology is presented for the detection of the
      initial stages of DNA fragmentation using pulsed-field gel electrophoresis or a
      combination of pulsed-field gel electrophoresis and conventional agarose gel
      electrophoresis that allows detection of the DNA ladder in the same sample. A new
      method for the detection of high molecular weight DNA fragments on conventional
      agarose gels is presented, together with a rationale for the analysis of DNA
      fragmentation during apoptosis.

PMID- 8292336
TI  - Death-induced changes to the nuclear matrix: the use of anti-nuclear matrix
      antibodies to study agents of apoptosis.
AB  - Using immunological techniques, we have shown for the first time that change in
      the nuclear matrix is an observable step in the cell death program. Immunometric
      assays detect soluble nuclear matrix proteins in the culture supernatants of
      cells killed by adriamycin, tumor necrosis factor and serum growth factor
      deprivation. Studies of cells killed by tumor necrosis factor and serum growth
      factor deprivation using dual immunofluorescent and 4'-6-diamidino-2-phenylindole
      (DAPI) staining detect many cells strongly positive for DNA that have little or
      no nuclear matrix protein. The staining pattern of cells killed by adriamycin is
      very different. There is good correspondence between the immunofluorescent and
      DAPI staining patterns indicating the presence of nuclear matrix proteins and
      DNA, although at a reduced ratio. It is concluded that the nuclear matrix changes
      are dependent on the agents that trigger cell death.

PMID- 8292337
TI  - Identification of the 72-kDa (MMP-2) and 92-kDa (MMP-9) gelatinase/type IV
      collagenase in preparations of laminin and Matrigel.
AB  - EDTA inhibitable type IV collagenolytic activity copurified with laminin
      preparations from the Engelbreth-Holm-Swarm (EHS) tumor. Several gelatinolytic
      and type IV collagenolytic matrix metalloproteinase (MMP) species were visualized
      in EHS laminin from three different sources by gelatin and type IV collagen
      substrate gel electrophoresis. Incubation with 4-aminophenylmercuric acetate and
      trypsin suggested that laminin contained both active and latent MMPs. EHS-derived
      reconstituted basement membrane, Matrigel, was found to possess an MMP profile
      identical to that of laminin. The presence of 72-kDa (MMP-2) and 92-kDa (MMP-9)
      gelatinases/type IV collagenases was demonstrated in laminin and Matrigel
      preparations by Western blot analysis. A rough quantitation of MMP-2 and MMP-9 in
      30 micrograms of laminin and 100 micrograms of Matrigel was between 0.3 and 0.6
      ng. The presence of these contaminants must be considered in experiments
      addressing the effects of EHS laminin or Matrigel on cell behavior and, in
      particular, stimulation of cellular proteolytic activity.

PMID- 8292338
TI  - A comparison of large-scale Sf9 insect cell growth and protein production:
      stirred vessel vs. airlift.
AB  - A simple and relatively inexpensive stirred-vessel system for the large-scale
      growth of insect cells (Sf9) is described. Sf9 cell growth in a stirred-vessel
      fermentor and an airlift fermentor were compared on the basis of maximum cell
      density and average population doubling time. Also, both fermentor systems were
      compared with respect to the large-scale production of a recombinant human
      protein (protein kinase C-eta). No significant differences in Sf9 cell growth or
      protein expression levels were apparent between the two fermentor systems.
      However, large differences in cost and scale-up of each system are discussed with
      respect to the large-scale production of recombinant proteins.

PMID- 8292339
TI  - Spectrofluorometric assay for hybridization of oligodeoxynucleotides using
      ethidium dimer.
AB  - A spectrofluorometric assay to detect hybridization of oligodeoxynucleotides is
      described. Ethidium dimer, which yields significant fluorescence enhancement when
      intercalated between adjacent base pairs, was employed as the probe. Maximum
      enhancement of fluorescence occurred at equimolar ratios of p(dA)20.p(dT)20,
      while negligible fluorescence occurred for either of these chains when not in the
      presence of the other. Base-paired oligonucleotides at concentrations as low as
      20 nM nucleotide could be detected, and the assay was linear over the tested
      range of 20 to 350 nM nucleotide. The method was used to measure the temperature
      dependent melting and hybridization of two self-complementary heteropolymers and
      the hybridization of a self-annealing (dG)20 preparation.

PMID- 8292340
TI  - SAW: a graphical user interface for the analysis of immunoglobulin variable
      domain sequences.
AB  - The Sequence Analysis Workshop (SAW) is an interactive program for sequence
      analysis of immunoglobulin variable domains. Sequences for SAW can be obtained
      from GenBank or from a standard text file. SAW can compare a variable domain to
      as many as 100 different sequences, calculate the extent of homology, sort the
      sequences by their degree of similarity, translate the nucleotide codons into
      amino acids and then display the results in either a graphical or text format.
      These comparisons allow the investigator to determine the likely germ-line
      progenitors of a variable domain and to visualize how it differs from other
      antibody genes by functional region. SAW supports replacement and silent site
      substitution analysis by either codon or region, thus providing rapid insight
      into the forces that have shaped mutations. The sequence comparisons can be
      printed out as an aid for paper analysis or for preparation of figures for
      publication. SAW is written in Microsoft C for use with the Microsoft Windows
      graphics environment. The use of color and graphics, the generation of subsidiary
      windows that contain the results of specific analyses and the mouse-driven
      control of the program make SAW an easy-to-use tool for immunoglobulin sequence
      comparison.

PMID- 8292341
TI  - Evaluation of storage phosphor imaging for quantitative analysis of 2-D gels
      using the Quest II system.
AB  - The advent of storage phosphor technology has been of considerable benefit to the
      imaging of gel-separated radiolabeled proteins due to the rapid and quantitative
      nature of the data acquisition process. Previously, times over one month were
      required to obtain fluorographs of the same gel to yield data of sufficient
      dynamic range for quantitative analysis of high-resolution two-dimensional (2-D)
      gels. As we are in the process of building a human 2-D gel protein database, and
      therefore have a high throughput of 2-D gels both to image and quantitate using
      the Quest II software, we undertook an evaluation of a storage phosphor imager,
      including an evaluation of signal fade. The results of this evaluation
      demonstrate the feasibility of using such a system, and we describe the
      procedures that allow us to use this technique for quantitative analysis of many
      complex 2-D gel patterns. These procedures include a useful batch printing
      program that allows printing of many images in a non-interactive mode. Examples
      will be presented of how autoradiography, using storage phosphor plates and the
      Quest II system, have enabled us to begin building a human 2-D gel protein
      database including posttranslational modification information, without the
      previous time constraints associated with such a project.

PMID- 8292342
TI  - Spreadsheet macros for coloring sequence alignments.
AB  - This article describes a set of Microsoft Excel macros designed to color amino
      acid and nucleotide sequence alignments for review and preparation of visual
      aids. The colored alignments can then be modified to emphasize features of
      interest. Procedures for importing and coloring sequences are described. The
      macro file adds a new menu to the menu bar containing sequence-related commands
      to enable users unfamiliar with Excel to use the macros more readily. The macros
      were designed for use with Macintosh computers but will also run with the DOS
      version of Excel.

PMID- 8292343
TI  - Using RNAFOLD to predict the activity of small catalytic RNAs.
AB  - A computer-assisted method for screening the relative activity of small catalytic
      RNAs is described. A series of four cis-acting variant sequence files are
      constructed based upon the RNA sequence of a trans-acting catalytic RNA under
      consideration. These files are individually folded into their lowest energy
      structure using a standard RNA folding algorithm. The compiled structures are
      assessed for their ability to form recognizable catalytic RNA secondary structure
      motifs. We demonstrate here that RNA sequences that do not readily fold into a
      cis-acting hammerhead ribozyme motif have trans-acting counterparts with reduced
      in vitro activity. This procedure should be useful in selecting the best
      candidate sequences in an mRNA to target for catalytic RNA cleavage.

PMID- 8292344
TI  - Isolation of RNA from cells in culture using Catrimox-14 cationic surfactant.
AB  - Traditional RNA isolation methods use chaotropic agents and anionic detergents to
      lyse cells and solubilize nucleic acids. In contrast, the cationic surfactant,
      Catrimox-14, lyses cells and simultaneously precipitates RNA, thereby protecting
      it from RNases. We describe and compare four methods for extracting RNA from
      cultured cells that differ in the technique used to extract the RNA from the
      precipitate. The first uses a high-salt solution (guanidinium isothiocyanate). In
      the second, the RNA is extracted with a polar solvent (formamide). The third
      involves conversion of the RNA to the sodium salt by treatment of the precipitate
      in situ with sodium acetate in ethanol. The fourth uses 2 M lithium chloride to
      convert the RNA in the pellet to the lithium salt in situ. We applied these
      methods to human leukemia cells growing in culture and each method resulted in
      excellent yields of RNA (typically 23 micrograms/million K562 cells, 13
      micrograms/million HL-60 cells) over a wide range of cell concentrations (1 x
      10(5) - 3 x 10(7)/ml) and of good to excellent quality as judged by agarose
      electrophoresis and UV absorbance data (OD260/280 1.90-2.05). The advantages and
      limitations of each method are discussed.

PMID- 8292345
TI  - Enhanced proliferation of peripheral blood mononuclear cells and tumor
      infiltrating lymphocytes in a plasma-derived cell culture fluid.
AB  - The proliferation and activation of murine and human T-lymphocytes in a high
      protein lymphocyte culture fluid (LCF) is compared to that of cells cultured in
      10% fetal bovine serum (FBS). Tumor-infiltrating lymphocytes (TIL) proliferate
      exponentially in the LCF for up to 46 days and generate cell numbers that are
      nearly 100,000-fold greater than cells cultured in FBS. This rapid growth of T
      cells in LCF could have an important impact in adoptive immunotherapy and gene
      therapy since cell growth is a limiting factor in these technologies.

PMID- 8292346
TI  - Isolation and expansion of tumor-infiltrating lymphocytes.

PMID- 8292347
TI  - Control of excess humidity in tissue culture CO2 incubators.

PMID- 8292348
TI  - Beta-galactosidase activity in bacteria measured by flow cytometry.

PMID- 8292349
TI  - A rapid method for extraction of DNA from agarose gels using a syringe.

PMID- 8292350
TI  - New cloning opportunities with the use of noncomplementary SfiI adaptors.

PMID- 8292351
TI  - Rapid screening of recombinant clones.

PMID- 8292352
TI  - Precipitation with KCl improves the chemical cross-linking of GST-fusion proteins
      to agarose after solubilization with SDS.

PMID- 8292353
TI  - Improved methods for the cultivation of strictly anaerobic, extremely
      thermophilic methanogens.
AB  - The strictly anaerobic, extremely thermophilic methanogens, Methanobacterium
      thermoautotrophicum Marburg and M. thermoautotrophicum delta H, have been
      cultivated in liquid culture and on solid medium in screw-top bottles, which
      permit continuous monitoring of the growth of the microorganisms. We have been
      able to routinely grow methanogens in medium containing bicarbonate, TRIS or 4
      morpholinepropanesulfonic acid (MOPS) buffers and three different sulfur sources
      (sulfide, sulfite and thiosulfate) at temperatures up to 70 degrees C and at
      pressures up to 35 psi while monitoring cell density or colony formation.

PMID- 8292354
TI  - Pulling springs to tune transduction: adaptation by hair cells.

PMID- 8292355
TI  - Bradykinin modulates potassium and calcium currents in neuroblastoma hybrid cells
      via different pertussis toxin-insensitive pathways.
AB  - In NG108-15 cells, bradykinin (BK) activates a potassium current (IK,BK) and
      inhibits the voltage-dependent calcium current (ICa,V). BK also stimulates a
      phosphatidylinositol-specific phospholipase C (PI-PLC). The subsequent release of
      inositol 1,4,5-trisphosphate and increase in intracellular calcium contribute to
      IK,BK, through activation of a calcium-dependent potassium current. In membranes
      from these cells, stimulation of PI-PLC by BK is mediated by Gq and/or G11, two
      homologous, pertussis toxin-insensitive G proteins. Here, we have investigated
      the role of Gq/11 in the electrical responses to BK. GTP gamma S mimicked and
      occluded both actions of BK, and both effects were insensitive to pertussis
      toxin. Perfusion of an anti-Gq/11 alpha antibody into the pipette suppressed
      IK,BK, but not the inhibition of ICa,V by BK. Thus, BK couples to IK,BK via
      Gq/11, but coupling to ICa,V is most likely via a different, pertussis toxin
      insensitive G protein.

PMID- 8292356
TI  - Independent regulatory elements in the nestin gene direct transgene expression to
      neural stem cells or muscle precursors.
AB  - Changes in intermediate filament gene expression occur at key steps in the
      differentiation of cell types in the mammalian CNS. Neuroepithelial stem cells
      express the intermediate filament protein nestin and down-regulate it sharply at
      the transition from proliferating stem cell to postmitotic neuron. Nestin is also
      expressed in muscle precursors but not in mature muscle cells. We show here that
      in transgenic mice, independent cell type-specific elements in the first and
      second introns of the nestin gene consistently direct reporter gene expression to
      developing muscle and neural precursors, respectively. The second intron contains
      an enhancer that functions in CNS stem cells, suggesting that there may be a
      single transcriptional mechanism regulating the CNS stem cell state. This
      enhancer is much less active in the PNS. The identification of these elements
      facilitates analysis of mechanisms controlling the switch in gene expression that
      occurs when muscle and brain precursors terminally differentiate.

PMID- 8292357
TI  - Functional diversity of GABA-activated Cl- currents in Purkinje versus granule
      neurons in rat cerebellar slices.
AB  - In rat cerebellar slices, we compared whole-cell recordings of spontaneous
      inhibitory postsynaptic currents (sIPSCs) with Cl- currents resulting from pulses
      of GABA (1 mM, < 2 ms) to outside-out patches from Purkinje and granule neurons.
      sIPSCs in Purkinje cells decayed with a single fast exponential, as previously
      reported, whereas in granule cells sIPSC decay was best described by the sum of a
      fast and a slow exponential curve, with a variable contribution of the slow
      component to the peak current. GABA pulses to nucleated patches from granule
      cells elicited Cl- currents with decays similar to sIPSC decays, whereas in
      patches from Purkinje neurons GABA pulses produced Cl- currents decaying largely
      with a fast component, but often followed by a slower exponential. GABA
      concentration steps produced rapidly desensitizing currents in patches from both
      cerebellar neurons. In distinct cerebellar neurons, specific functional
      properties of GABAA receptors may relate to the presence of distinct receptor
      subtypes.

PMID- 8292358
TI  - An important role of heparan sulfate proteoglycan (Perlecan) in a model system
      for the deposition and persistence of fibrillar A beta-amyloid in rat brain.
AB  - A consistent rat model for the study of the consequences of congophilic and
      fibrillar A beta-amyloid in brain has been developed. One hundred percent of
      animals receiving infusions of synthetic beta-amyloid protein (A beta 1-40) plus
      a specific heparan sulfate proteoglycan (HSPG) for 1 week or 7 weeks (following 2
      week infusions) demonstrated Congo red and thioflavin S-positive deposits
      adjacent to the infusion site. Extracellular amyloid fibrils were identified by
      electron microscopy and were immunogold decorated with A beta antibody.
      Significant increases in Congo red staining were observed in animals infused with
      A beta plus HSPG versus those infused with only A beta. Infusion of A beta alone
      was variable with respect to congophilic amyloid persistence, which occurred in
      50% of animals and only when endogenous HSPGs accumulated at A beta deposition
      sites. By 7 weeks, only animals infused with A beta plus HSPG demonstrated
      compaction of the Congo red material from amorphous, wispy deposits (at 1 week)
      to stellate deposits resembling a Maltese cross. These spherical amyloid deposits
      were very similar to Congo red-stained amyloid plaques in human Alzheimer's
      disease brain, and in vitro data suggest that they were probably formed in vivo
      following interactions with endogenous brain components.

PMID- 8292359
TI  - The gene poxn controls different steps of the formation of chemosensory organs in
      Drosophila.
AB  - The gene poxn codes for a transcriptional regulator that specifies poly
      innervated (chemosensory), as opposed to mono-innervated (mechanosensory), organs
      in Drosophila. The ectopic expression of poxn during metamorphosis results in a
      transformation of the morphology and central projection of adult mechanosensory
      organs toward those of chemosensory organs. Here we show, by electron microscopy
      analysis of normal and transformed bristles and by Dil labeling of the
      innervating neurons, that poxn also controls the number of neurons. To determine
      whether poxn can transform not only the sense organ precursor cells but also
      their daughter cells, we examine the effects of the ectopic expression of poxn at
      different stages of the lineage, and we conclude that poxn can act at a late
      stage to affect the fate of the undifferentiated neuron.

PMID- 8292360
TI  - How quickly can GABAA receptors open?
AB  - We have examined GABAA receptor activation by making rapid applications of GABA
      to outside-out patches excised from cultured postnatal rat cerebellar neurons.
      The rate of development of current increases with increasing GABA concentration
      from a low to a high concentration asymptote. The low concentration asymptote is
      about 10 s-1 for patches taken from granule cells and 4 s-1 for patches from
      Purkinje cells. The high concentration asymptote is about 6000 s-1 for patches
      taken from either granule cells or Purkinje cells. The high concentration
      asymptote gives an estimate of the fastest rate at which these channels can open
      and indicates that agonist binding steps are not rate limiting. The concentration
      dependence of the development of current indicates that more than one GABA
      molecule is bound to most receptors with open channels and that the final binding
      step is of low affinity (about 500 microM). A comparison with GABA-mediated
      postsynaptic currents suggests that the properties of the GABAA receptor play a
      major role in determining the shape of inhibitory synaptic responses and that the
      cleft concentration of GABA reaches at least 500 microM.

PMID- 8292361
TI  - A Shab potassium channel contributes to action potential broadening in
      peptidergic neurons.
AB  - We have cloned the gene for a potassium channel, Aplysia Shab, that is expressed
      in the bag cell neurons of Aplysia. The voltage dependence and kinetics of the
      Aplysia Shab current in oocytes match those of IK2, one of the two delayed
      rectifiers in these neurons. Like IK2, but in contrast with other members of the
      Shab subfamily, the Aplysia Shab current inactivates within several hundred
      milliseconds. This inactivation occurs by a process whose properties do not match
      those previously described for C-type and N-type mechanisms. Neither truncation
      of the N-terminus nor block by tetraethylammonium alters the time course of
      inactivation. By incorporating the characteristics of Aplysia Shab into a
      computational model, we have shown how this current contributes to the normal
      enhancement of action potentials that occurs in the bag cell neurons at the onset
      of neuropeptide secretion.

PMID- 8292362
TI  - Selective up-regulation of an NMDA receptor subunit mRNA in cultured cerebellar
      granule cells by K(+)-induced depolarization and NMDA treatment.
AB  - High KCI or NMDA treatment promotes the survival of cultured neonatal cerebellar
      granule cells, and these cells become sensitive to NMDA toxicity after prolonged
      K+ depolarization. Following both treatments, the NMDA receptor increases, as
      assessed by fura-2 fluorescence analysis of NMDA receptor-mediated intracellular
      Ca2+ increase. Northern analysis indicates that both treatments specifically up
      regulate NMDAR2A subunit mRNA through an increase in resting intracellular Ca2+
      concentration. Antisense oligonucleotide analysis further indicates that NMDAR2A
      mRNA up-regulation is responsible for NMDA receptor induction. Our results
      demonstrate that regulation of a specific NMDA receptor subunit mRNA governs NMDA
      receptor induction, which is thought to play an important role in granule cell
      survival and death.

PMID- 8292363
TI  - Kinetics of GABAB receptor-mediated inhibition of calcium currents and excitatory
      synaptic transmission in hippocampal neurons in vitro.
AB  - The time courses of the gamma-aminobutyric acid type B (GABAB) receptor-mediated
      inhibition of excitatory synaptic transmission and of action potential-evoked
      calcium currents were studied in hippocampal neurons in vitro with step-like
      changes of a saturating baclofen concentration. Inhibition mediated by
      postsynaptic GABAB receptors was excluded pharmacologically. Both presynaptic
      inhibition and reduction of calcium currents developed and declined exponentially
      with similar time constants of about 0.2 and 3 s, respectively. The close
      correlation of the time courses indicates that fast, G protein-mediated
      depression of voltage-gated calcium channels and thus direct reduction of the
      presynaptic calcium influx may contribute to the GABAB receptor-induced
      inhibition of excitatory synaptic transmission in hippocampal neurons in vitro.

PMID- 8292364
TI  - Advances in propofol pharmacokinetics and pharmacodynamics.

PMID- 8292365
TI  - The laryngeal mask airway for outpatient anesthesia.
AB  - The LMA has been commercially available since 1988, and in the United States
      since 1992. The device combines several advantages of endotracheal tubes and face
      masks and may be used in many situations where either device was previously used
      routinely. Its principal advantage is a clearer airway, without the morbidity
      associated with endotracheal intubation. Although not suitable for all patients
      and procedures, the LMA has become widely used in all other countries where it is
      available. Many of the surgical procedures for which the LMA is most suited are
      performed in outpatients, and we expect this device will soon become popular in
      carefully selected cases in this country.

PMID- 8292366
TI  - Impact of newer drugs and techniques on the quality of ambulatory anesthesia.
AB  - Recent pharmacologic and technologic advances in anesthesia and surgery allow
      outpatients with complex medical problems to undergo a wide variety of diagnostic
      and surgical procedures on an ambulatory basis. Increasingly, however, anesthesia
      practitioners, as well as pharmacy and therapeutic committees, are demanding
      proof that a new, more costly drug or medical device is superior to existing
      products in achieving its desired effect, is associated with fewer adverse
      effects, enhances efficiency, and reduces health care costs. The new field of
      pharmacoeconomics has emphasized the importance of cost-effectiveness analyses
      that consider both direct and indirect costs of newer drugs and therapeutic
      modalities. As new biomedical technology is introduced to facilitate the
      perioperative management of patients (e.g., computerized anesthesia information
      management systems), evidence that these systems enhance our ability to continue
      to provide high-quality, cost-effective health care will assume increasing
      importance. Limitations in health care resources necessitate a careful
      reevaluation of our clinical practices with respect to choice of drugs, supplies,
      equipment, and even discharge criteria. Ambulatory anesthesia and surgery will
      continue to increase because of the potential cost savings for patients
      undergoing elective operations on an outpatient basis. However, the challenge we
      face will be to continue to provide high-quality anesthesia care at a reduced
      cost. A careful examination of commonly accepted (but unproven) clinical practice
      patterns will be necessary to meet this challenge.

PMID- 8292367
TI  - Common problems in pediatric ambulatory surgery: upper respiratory infection,
      heart murmur, or sickle-cell disease.

PMID- 8292368
TI  - Nondepolarizing relaxants: new concepts and new drugs.
AB  - Less than a decade ago, the only nondepolarizing neuromuscular blocking drugs
      available to the anesthetist were traditional long-acting drugs such as
      pancuronium and d-tubocurarine. The revolution that began 10 years ago in our use
      of relaxants promises to continue unabated into the next decade. Changes in our
      clinical use of these drugs will be sparked not just by the introduction of new
      drugs but also by a greater understanding of the pharmacokinetic/pharmacodynamic
      principles that govern onset and recovery.

PMID- 8292369
TI  - Drug reversal: Benzodiazepine receptors and antagonists.

PMID- 8292370
TI  - The role of ondansetron and other antiemetics in ambulatory anesthesia.

PMID- 8292371
TI  - New modalities in outpatient postoperative pain management.

PMID- 8292372
TI  - Are discharge criteria changing?
AB  - The safe and expeditious conduct of ambulatory surgical care can succeed only by
      careful selection of patients and surgical procedures, appropriate intraoperative
      and postoperative anesthesia care, and prudent and timely discharge of patients.
      Practical discharge criteria or a postanesthesia discharge scoring system should
      be implemented in every ambulatory surgery center to ensure safe recovery and
      discharge after anesthesia. The PADSS is simple, practical, and easy to remember.
      It provides an uniform assessment of all patients, it may have added medicolegal
      value, and it establishes a routine of repeated reevaluation of home readiness.
      We recommend using the postanesthesia recovery score (Aldrete score) to evaluate
      the initial recovery of the patient. Once the Aldrete score is met, home
      readiness can be evaluated by the PADSS or modified PADSS (Tables 3 and 4). If
      the patient satisfies the criteria of the PADSS or modified PADSS, he or she can
      be discharged home. At the Toronto Hospital, we have discharged 30,000 patients
      home safely with the PADSS. However, any discharge criteria scoring system must
      be used with common sense and clinical judgment. Home readiness does not mean
      street fitness. Further studies on adverse outcomes after discharge and the
      return to normal function (e.g., work readiness) are warranted.

PMID- 8292373
TI  - Neutrophils increase volume during migration in vivo and in vitro.
AB  - Neutrophils increase volume (approximately 15%) when stimulated in suspension,
      but whether a similar alteration occurs in vivo during migration is unknown. We
      measured neutrophil volume using serial 0.5-micron sections and three-dimensional
      reconstruction of rabbit neutrophils migrating into inflammatory lesions in lung
      and abdominal wall in vivo and of human neutrophils migrating across collagen
      gels in vitro. An inflammatory response was induced by local instillation of C5a
      in vivo or generating a gradient of FMLP in vitro. In the lung, neutrophils
      reconstructed within the vascular space, either in arterioles (158 microns3),
      capillaries (128 microns3), or venules (135 microns3), were of similar volume,
      while those in the airspace were markedly larger (266 microns3). Neutrophils that
      migrated into the abdominal wall (150 microns3) were also significantly larger
      than those in the abdominal wall vasculature (100 microns3). Human neutrophils
      induced to migrate into collagen gels by FMLP were significantly larger (290
      microns3) than those that did not migrate (204 microns3). We conclude from these
      studies that migration of rabbit neutrophils in vivo or human neutrophils in
      vitro is associated with a substantial increase in volume. We speculate that
      these findings hold promise for elucidation of the mechanisms of neutrophil
      migration.

PMID- 8292374
TI  - Cryptogenic organizing pneumonia: increased expression of interleukin-8 and
      fibronectin genes by alveolar macrophages.
AB  - Cryptogenic organizing pneumonia (COP) is a fibrotic process that primarily
      involves the alveolar spaces, alveolar ducts, and small conducting airways. The
      pathogenesis is not understood. Recent histopathologic studies have shown that
      during the cellular phase of COP, fibronectin deposits are present in the lung.
      Moreover, a neutrophil alveolitis is frequently seen in COP. Little is known
      about the involvement of alveolar macrophages in the pathogenesis of COP.
      However, alveolar macrophages are the principal resident cells in the airways,
      and they are thought to play a central role in the fibrotic process by virtue of
      their ability to express and release cytokines such as interleukin-8 (IL-8; a
      neutrophil chemotactic factor) and fibronectin (FN; a fibrogenic matrix
      associated protein). We have quantified the spontaneous gene expression of IL-8
      and FN by alveolar macrophages from five nonsmoking individuals with COP and
      compared them with 10 normal, healthy volunteers (five smokers, five nonsmokers).
      Expression of IL-8 and FN was measured by a quantitative assay employing reverse
      transcription of mRNA and the polymerase chain reaction. beta-actin mRNA
      expression was quantified as an internal standard, and the expression of FN and
      IL-8 transcripts was calculated as a ratio with beta-actin. The mean +/- SEM of
      the IL-8/beta-actin ratio in alveolar macrophages from patients with COP was 0.45
      +/- 0.07, which was significantly higher than the level from either normal
      smokers (0.19 +/- 0.02, P = 0.008) or normal nonsmokers (0.16 +/- 0.01, P =
      0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292375
TI  - Tannin inhibits cAMP pathways in bovine airway epithelium.
AB  - Tannin, isolated from aqueous extracts of cotton bracts, inhibits chloride
      secretion in airway epithelial cells. The effect of tannin on the epinephrine-
      and bradykinin-stimulated rise in intracellular free calcium and cyclic adenosine
      monophosphate (cAMP) was examined using bovine tracheal epithelial cells in
      suspension and culture. Basal intracellular calcium levels were 33 +/- 11 nM
      (mean +/- SEM, n = 54) and increased 13- to 15-fold after addition of epinephrine
      (10(-6) M) or bradykinin (2 x 10(-6) M). Tannin pretreatment blunted the
      subsequent response to epinephrine beginning at a tannin concentration of 10
      micrograms/ml. Pretreatment with 100 micrograms/ml tannin completely inhibited
      the rise in intracellular free calcium in response to epinephrine but had no
      effect on the calcium response to bradykinin. In the absence of tannin, both
      bradykinin and epinephrine increased intracellular levels of cAMP. At a tannin
      concentration of 10 micrograms/ml, tannin inhibited the rise in intracellular
      cAMP in cells stimulated with either epinephrine or bradykinin but had no effect
      on bradykinin-stimulated prostaglandin E2 release. Tannin alone (10
      micrograms/ml) increased prostaglandin E2 release. In other studies, tannin
      inhibited epinephrine binding to airway epithelial cells in a dose-dependent
      manner. R(o) decreased from 948 +/- 69 fmol/mg protein under control conditions
      (n = 4) to 587 +/- 131 fmol/mg protein in the presence of 25 micrograms/ml tannin
      (n = 3). Tannin had no effect upon the Kd for epinephrine binding (132 +/- 12
      pM). Tannin had no effect on bradykinin binding to airway epithelial
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292376
TI  - Identification and functional characterization of the bovine manganous superoxide
      dismutase promoter.
AB  - Manganous superoxide dismutase (MnSOD) gene expression is stimulated by
      endotoxin, tumor necrosis factor, and interleukin-1, agents thought to cause
      cellular damage through intracellular generation of reactive oxygen species. To
      study the molecular mechanisms underlying the induction of MnSOD mRNA by these
      stimuli, we cloned a bovine MnSOD cDNA and used it to isolate the promoter region
      of the bovine MnSOD gene. A 14 kb genomic DNA fragment (lambda BS1) containing
      the first and second exons and 5' flanking region of the gene was characterized.
      The transcription start site was determined by primer extension and S1 nuclease
      protection assays and found to be 88 bp upstream of the translation initiation
      codon. The sequence of approximately 1 kb of DNA upstream of the start site was
      determined and examined for potential regulatory elements. DNA immediately
      upstream of the transcription start site was GC-rich and contained two AP-2 and
      eight Sp-1 consensus sequences. It did not contain either a CCAAT or TATA box. A
      956 bp fragment of this DNA fragment was transcriptionally active when fused to a
      luciferase reporter gene and transfected into both bovine pulmonary artery
      endothelial and hamster insulinoma tumor cells. Transfection analysis of three
      additional deletion mutants, whose 5' end-points were -317, -182, and -70 bp,
      respectively, showed a step-like reduction in transfection efficiency, suggesting
      the presence of regulatory elements throughout this DNA fragment that contribute
      to transcriptional activity of the MnSOD promoter. Despite the high homology of
      the bovine MnSOD cDNA to other mammalian MnSODs, the promoter sequences of bovine
      and rat MnSOD genes showed a virtual lack of similarity.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8292377
TI  - A non-radioisotopic method for tracing neutrophils in vivo using 5'-bromo-2'
      deoxyuridine.
AB  - Polymorphonuclear leukocytes (PMN) labeled in vivo with 5'-bromo-2'-deoxyuridine
      (BrdU) in donor animals were transferred to recipients to determine the rate of
      clearance of labeled PMN from the circulation, their margination within the
      vascular space, and migration into Streptococcus pneumoniae-induced inflammatory
      sites. The donor animals received intravenous infusions at 25 mg/kg/day of BrdU
      for 7 days when cytospins of leukocyte-rich plasma (LRP) showed that 80 +/- 2.3%
      PMN were labeled. The BrdU labeled cells were then transfused to serum-compatible
      recipients as either whole blood, leukocyte-rich plasma, or PMN purified from an
      equal volume of whole blood. Twenty-four hours after transfer, the distribution
      of BrdU-labeled PMN in the lung, liver, spleen, bone marrow, and gut was
      determined morphometrically and by Southern blot analysis of DNA extracted from
      these organs. BrdU-labeled PMN transfused as either LRP or purified PMN provided
      no advantage over transfusing whole blood. The half-life of BrdU-labeled PMN in
      the recipient circulation after transfusing whole blood was 270.4 min (95%
      confidence intervals, 248.5 to 296.4 min). The majority of the BrdU-labeled DNA
      was found in the spleen, where DNA analysis showed that the white blood cells
      underwent programmed cell death by apoptosis. Four hours after infection with S.
      pneumoniae and 1 h after transfusion of labeled whole blood, BrdU-labeled PMN had
      migrated into the infected sites. We conclude that transfer of BrdU PMN in whole
      blood provides a simple, effective method of tracing labeled PMN in vivo.

PMID- 8292378
TI  - Aerosol and intravenous transfection of human alpha 1-antitrypsin gene to lungs
      of rabbits.
AB  - In vivo gene transfer to the lungs is possible either by an intravenous or an
      airway route of administration. A plasmid containing the recombinant human alpha
      1-antitrypsin (h alpha 1AT) gene and a cytomegalovirus promoter complexed to
      cationic liposomes was given either intravenously or by aerosol to New Zealand
      White rabbits. Both routes of administration resulted in successful transfection
      and expression of the h alpha 1AT gene. h alpha 1AT mRNA and protein were
      detected for at least 7 days. Immunohistochemical staining showed h alpha 1AT
      protein in the pulmonary endothelium following intravenous administration, in
      alveolar epithelial cells following aerosol administration, and in the airway
      epithelium by either route. After intravenous injection of radiolabeled plasmids,
      autoradiographs showed localization of plasmid in endothelial cells, especially
      at arterial bifurcations, and at the alveolar level. A plasmid-liposome delivery
      system for gene therapy to the lungs may permit targeting of the DNA to subsets
      of lung cells by selection of the route of delivery and may permit a broad
      application of gene therapy to acute as well as chronic diseases.

PMID- 8292379
TI  - Regulation of surfactant protein D expression by glucocorticoids in vitro and in
      vivo.
AB  - SP-D is a recently described lung-associated protein that is produced by alveolar
      type II cells and may function in pulmonary host defenses. Since little is known
      regarding the hormonal regulation of SP-D, and since the other surfactant
      proteins (SP-A, SP-B, and SP-C) are known to be regulated by glucocorticoids, we
      sought to determine the effects of glucocorticoids on SP-D mRNA and protein
      expression, both in vitro and in vivo, in the fetal rat lung. In vitro
      experiments were performed on lung explants from fetuses on gestational day 15 or
      18. Explants were cultured in serum-free conditions with or without
      hydrocortisone for 3 days. SP-D mRNA expression was evaluated by Northern blot
      analysis. SP-D protein expression was analyzed using a polyclonal antibody
      against SP-D and standard immunohistochemical techniques. The expression of SP-D
      mRNA increased in fetal day 15 explants but remained unchanged in fetal day 18
      explants cultured without the addition of hydrocortisone, compared with in vivo
      controls. The addition of hydrocortisone resulted in increases in SP-D mRNA
      expression at both gestational ages. This pattern of SP-D mRNA expression was
      compared with the expression of the other surfactant proteins and found to be
      most similar to that of SP-B. In vivo experiments were performed using maternal
      administration of dexamethasone (1 mg/kg) or an equal volume of saline on fetal
      days 15, 16, and 17 or on fetal day 17 with sacrifice on fetal day 18.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8292380
TI  - Betamethasone activation of CTP:cholinephosphate cytidylyltransferase in vivo is
      lipid dependent.
AB  - Glucocorticoids increase surfactant phosphatidylcholine synthesis, in part, by
      stimulating the rate regulatory enzyme CTP:cholinephosphate cytidylyltransferase.
      This enzyme exists in mammalian lung cytosol as an active lipoprotein form (H
      form) and an inactive apoprotein (L-form) species. We administered betamethasone
      to pregnant rats to examine the mechanisms for glucocorticoid stimulation of
      cytidylyltransferase activity in fetal lung. The hormone stimulated cytosolic
      activity threefold, and this effect was nearly abolished after lipid extraction.
      The addition of lipid extracts isolated from betamethasone-treated cytosolic
      preparations to L-form species increased enzyme activity to a greater extent than
      lipid extracts from control lungs. Further, the glucocorticoid increased the
      proportion of H-form activity from 34 to 55% of the total activity in the fetal
      lung cytosol. These changes were associated with a marked decrease in the
      activity of the L-form species. Analysis of the lipid composition of the H-form
      revealed that betamethasone increased the content of lipid activators, including
      phosphatidylglycerol and fatty acids. These observations provide evidence that
      glucocorticoid stimulation of CTP:cholinephosphate cytidylyltransferase in vivo
      is mediated by a conversion of the inactive form (L-form) to the active species
      (H-form). These studies further emphasize the critical role of lung lipids in
      mediating the glucocorticoid activation of this enzyme.

PMID- 8292381
TI  - Activation of alveolar macrophages by native and synthetic collagen-like
      polypeptides.
AB  - Interstitial connective tissue fragments are known to be chemotactic for
      neutrophils and these have been implicated in mediating the migration of
      inflammatory cells to the lung following injury. In the present studies, we
      determined if degradation products of collagen also induced chemotaxis and
      functional activation of alveolar macrophages. For these studies, we used bovine
      dermal collagen digested with bacterial collagenase or cyanogen bromide and small
      molecular weight synthetic polypeptides containing proline (Pro), glycine (Gly),
      and hydroxyproline (Hyp). We found that collagenase or cyanogen bromide digests
      of native collagen, as well as synthetic polypeptides containing Pro and Gly in
      the pentameric (Pro-Pro-Gly)5 form, were potent chemoattractants for rat alveolar
      macrophages inducing migration in the nanomolar concentration range. We also
      found that native and synthetic collagen peptides stimulated the release of
      superoxide anion and hydrogen peroxide, as well as elastase and gelatinase
      release from alveolar macrophages. These effects were dose and time dependent,
      reaching a maximum after 72 h with 0.1 to 1 microM peptides. In contrast to
      chemotaxis, synthetic peptides containing Hyp also stimulated reactive oxygen
      intermediate and elastase release from the cells. Although the pentameric and
      decameric forms of the synthetic peptides were equally effective in stimulating
      elastase release, (Pro-Pro-Gly)5 and (Pro-Hyp-Gly)5 peptides were more active in
      inducing a respiratory burst. We also determined if alveolar macrophages were
      activated for cytotoxicity by collagen peptides. Treatment of the macrophages
      with native collagen digests or (Pro-Pro-Gly)5 was found to induce cytotoxicity
      of these cells towards both transformed and nontransformed rat-derived
      targets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292382
TI  - Interferon-gamma increases cytoplasmic motility of alveolar macrophages via
      nitric oxide-dependent signaling pathways.
AB  - The effects of interferon-gamma (IFN-gamma) were investigated on cytoplasmic
      motility of alveolar macrophages (AM) from rat lungs in vitro. Cytoplasmic
      motility was examined by measuring remnant field strength from the cell surface
      of AM containing Fe3O4 particles, and the relaxation rate (lambda 0; min-1),
      which is related to cytoplasmic motility, was determined. IFN-gamma caused an
      increase in lambda 0 in a concentration-dependent fashion with the maximal effect
      at 1,000 U. Dibutyryl cyclic GMP (db cyclic GMP; 10(-3) M) mimicked IFN-gamma
      induced effects, but db cyclic AMP (10(-3) M) decreased lambda 0. IFN-gamma
      (1,000 U)-induced increases in lambda 0 were concentration-dependently inhibited
      by NG-monomethyl-L-arginine (L-NMMA) with complete inhibition of a concentration
      of 10(-4) M and were also completely inhibited by either methylene blue (10(-5)
      M) or KT 5823 (10(-5) M), a specific inhibitor of protein kinase G. IFN-gamma
      (1,000 U) caused significant nitrite (NO2-) production from the control values of
      0.2 +/- 0.1 to 10.0 +/- 0.2 microM/24 h per 10(6) cells (P < 0.001, n = 10), and
      this increase in NO2- production by IFN-gamma (1,000 U) was completely inhibited
      by L-NMMA (10(-4) M). IFN-gamma caused a concentration-dependent increase in a
      filamentous-actin (F-actin) content with the maximal effect at 1,000 U. db cyclic
      GMP (10(-3) M) mimicked IFN-gamma induced effects on F-actin formation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8292383
TI  - HIV-1 in human alveolar macrophages from infected patients is latent in vivo but
      replicates after in vitro stimulation.
AB  - It has been demonstrated that alveolar macrophages (AM) are permissive for human
      immunodeficiency virus (HIV-1) after in vitro infection. However, data concerning
      in vivo infection of AM by HIV-1 still conflict. Therefore, we investigated AM
      collected by bronchoalveolar lavage from 15 HIV-1-infected patients. HIV-1 p24
      and Gp120 antigens and viral RNA were not detected by immunocytochemistry and in
      situ hybridization, respectively, using 35S-labeled 3 kb Pol-Env, 0.350 kb Gag,
      and 0.150 kb U5 LTR cRNA probes. In contrast, when using polymerase chain
      reaction on DNA extracted from purified AM, HIV-1 DNA was detected in the seven
      patients tested. After short-term culture of alveolar cells from three HIV-1
      infected patients and in vitro stimulation with granulocyte/macrophage colony
      stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha), HIV-1
      replication was observed in most of the AM. These results demonstrate that AM are
      latently infected by HIV-1 in vivo but are not a site for viral replication. In
      contrast, HIV-1 replication occurs when AM are withdrawn from their local
      environment, enhanced by GM-CSF and TNF-alpha stimulation. This suggests either a
      negative control or an inadequate stimulation of HIV-1 replication in the
      alveolar environment.

PMID- 8292384
TI  - Selection of pulmonary CD4-, CD8-, alpha beta+ T cells expressing V beta 8 T cell
      receptors.
AB  - The double negative (CD4-CD8-) alpha beta+ T cells constitute about 20% of all
      alpha beta+ T cells in murine lungs. We find that in BALB/c mice 60% of the
      double negative alpha beta+ pulmonary T cells express receptors of the V beta 8
      family whereas only 33% of single positive (CD4+/CD8+) pulmonary T cells express
      V beta 8. However, in C57BL/6 mice, equal frequencies (25%) of double negative
      and single positive alpha beta+ pulmonary T cells express V beta 8. The high
      frequency of double negative V beta 8+ pulmonary T cells is dominantly inherited
      in (C57BL/6 X BALB/c) F1 offsprings. Further studies exclude the involvement of
      classic MHC region genes in determining the level of V beta 8 usage among double
      negative pulmonary T cells. Upon exposure to mycobacterial antigens, double
      negative alpha beta+ pulmonary T cells are co-enriched in vitro in parallel with
      gamma delta+ T cells.

PMID- 8292385
TI  - Expression and regulation of macrophage inflammatory protein-1 alpha by murine
      alveolar and peritoneal macrophages.
AB  - A number of disease states are characterized by the accumulation of inflammatory
      cells at the site of tissue injury. Mononuclear phagocytes (M phi) represent key
      cellular mediators of inflammation via the production of regulatory and
      chemokinetic cytokines. One such cytokine, macrophage inflammatory protein-1
      alpha (MIP-1 alpha), has been shown to be one of the major inducible chemotaxins
      expressed from murine macrophage cell lines (RAW 264.7). We postulated that MIP-1
      alpha is a major monocyte chemoattractant produced by resident M phi, and the
      magnitude of production of this chemotaxin may depend upon the specific
      population of M phi studied. To test this hypothesis, we isolated alveolar
      macrophages (AM phi) and peritoneal macrophages (PM phi) from CD-1 mice by
      bronchoalveolar and peritoneal lavage, respectively. Recombinant murine MIP-1
      alpha accounted for significant neutrophil chemokinetic rather than chemotactic
      activity, as assessed by checkerboard analysis. LPS-stimulated AM phi-derived
      monocyte chemotactic activity (MCA) was significantly neutralized by specific
      rabbit anti-murine MIP-1 alpha serum. In contrast, PM phi-derived conditioned
      media failed to produce MCA attributable to MIP-1 alpha. The production of MIP-1
      alpha was then characterized from both AM phi and PM phi. While unstimulated AM
      phi and PM phi failed to express MIP-1 alpha mRNA, both AM phi and PM phi
      challenged with lipopolysaccharide (LPS) expressed MIP-1 alpha mRNA in a time
      dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292386
TI  - Strain increases airway smooth muscle cell proliferation.
AB  - Airway smooth muscle (ASM) cell hyperplasia is a common finding in lung diseases
      in which increased transpulmonary pressure is necessary for adequate ventilation.
      The extent to which mechanical deformation of ASM cells contributes to the
      observed hyperplastic changes has not been addressed. To determine if cyclic
      stretch alters ASM cell proliferation and protein content in vitro, canine ASM
      cells were cultured on collagen-coated silastic membranes, subjected to a stretch
      relaxation regimen, and compared with cultured cells on a rocking platform or
      with control (unmanipulated) cells. During the log phase of cell growth, cyclic
      stretch resulted in increased cell numbers (P < 0.001). Incorporation of
      [3H]thymidine ([3H]TdR) was assessed after 5 or 14 days in culture during 12-h
      pulse in stretched, rocked, and control cells. Incorporation of [3H]TdR per cell
      was elevated in stretched cells when compared with either rocked or control cells
      at 5 days but not 14 days. Total cellular protein content per well determined
      after cells had reached confluence was greater in stretched cells than in the
      controls (74.2 +/- 7.9 stretched versus 49.1 +/- 5.6 control versus 51.1 +/- 6.5
      rocker; microgram/10(5) cells; P < 0.05). Transmission electron microscopic
      observations of stretched cells suggested increased concentrations of
      myofilaments compared with control cells. These observations suggest that stretch
      may contribute to increased ASM hyperplasia and airway resistance.

PMID- 8292387
TI  - Long-term exposure to norepinephrine results in down-regulation and reduced mRNA
      expression of pulmonary beta-adrenergic receptors in guinea pigs.
AB  - We studied the down-regulation of beta 2-adrenoceptors in guinea pig lung after
      chronic exposure to a beta-agonist. Guinea pigs were exposed to either
      norepinephrine (NE) or vehicle for 7 days. The density and affinity of beta
      adrenoceptors were determined by Scatchard analysis of [125I]cyanopindolol
      binding in a lung membrane preparation and beta 1- and beta 2-adrenoceptor
      subtypes were studied in the presence of 0.1 microM ICI 118,551, a selective beta
      2-adrenoceptor antagonist, or 0.1 microM CGP 20712 A, a selective beta 1
      adrenoceptor antagonist, respectively. beta 2-Adrenoceptor mRNA was examined by
      Northern blot analysis. The tissue distribution of beta 2-adrenoceptors and of
      beta 2-adrenoceptor mRNA in lung after NE infusion were determined using receptor
      autoradiography and in situ hybridization, respectively. The functional
      significance of the decrease in beta 2-adrenoceptor was tested by measuring the
      relaxation response to a beta 2-agonist in isolated parenchymal strips. NE
      treatment resulted in decreases of 75 +/- 9%, 84 +/- 4%, and 66 +/- 9% of total
      beta-, beta 1-, and beta 2-adrenoceptors in the lung, compared with control
      animals. The administration of NE had only minimal effects on the dissociation
      constant (Kd) of the receptor for the radioligand. beta 2-Adrenoceptors mRNA was
      decreased by 46 +/- 13% after NE treatment. There was a correspondence between
      the distribution of beta 2-adrenoceptors and beta 2-adrenoceptor mRNA
      localization in both control and NE-treated guinea pigs. NE treatment reduced
      alveolar beta 2-adrenoceptors by 70 +/- 3% and its mRNA expression by 78 +/-
      5%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292388
TI  - Complementation assay of primer protein: gene expression systems of plasmid
      vectors support the infection of suppressor sensitive mutant phages M2 and phi
      29.
AB  - Two different expression systems of genes of primer proteins (pE for phage M2,
      and p3 for phi 29) were constructed to study the protein primed DNA replication
      of Bacillus phages M2 and phi 29. In one system, expression of the genes was
      under the control of the inducible spac promoter, whereas in the other system,
      the expression was under the control of the constitutive promoter in plasmid
      pUB110. Complementation tests in vivo were performed between the primer proteins
      expressed by these systems and mutant phages having suppressor sensitive
      mutations in the genes of the primer proteins. The phages M2 susE and phi 29 sus3
      were complemented by pE and p3 expressed by the systems, respectively. However,
      the complementation and apparent phage DNA synthesis were not detected in the
      combinations between susE of phage M2 and p3 of phage phi 29, and vice versa.
      Although pE and p3 proteins exhibited structurally and functionally similar
      characteristics, these proteins showed species specificity in the protein primed
      DNA replication of bacteriophages M2 and phi 29.

PMID- 8292389
TI  - Analysis of mitochondrial DNA in two species of the bipectinata species complex
      of Drosophila.
AB  - Drosophila bipectinata and D. malerkotliana are members of the bipectinata
      species complex of the ananassae subgroup in the melanogaster species group of
      Drosophila. The mtDNA from 18 isofemale strains of these species was analyzed,
      using 13 restriction endonucleases. Altogether, eight mtDNA haplotypes were
      detected, of which the haplotype 1B was shared by the two species. Restriction
      cleavage map of mtDNA of these species was constructed. The net nucleotide
      substitutions per site calculated between these species was found to be 0.0002.
      This value appeared to be relatively much lower than expected at the
      interspecific level, even lower than that reported between two subspecies of
      Drosophila despite both being good species. This extreme closeness of their
      mtDNAs is discussed in the light of recent findings.

PMID- 8292390
TI  - A novel mutation involved in the mitotic checkpoint in the fission yeast
      Schizosaccharomyces pombe.
AB  - The cps8 mutation which confers supersensitivity to a spindle poison, Isopropyl N
      3-chlorophenyl carbamate (CIPC), in the fission yeast Schizosaccharomyces pombe
      was investigated. The cps8 mutant accumulated enlarged multinucleate cells in the
      stationary phase under normal growth conditions. The mutant was highly lethal at
      36.5 degrees C in a fresh growth medium but not in a saline solution where the
      cell cycle ceases quickly. Lethality at high temperature was significantly
      suppressed by cdc1 or nda2 mutation which blocks nuclear division, but not by
      hydroxyurea treatment or cdc22 mutation which blocks DNA synthesis. A cdc10 cps8
      double mutant remained lethal to high temperature, suggesting this double mutant
      to bypass the requirement for cdc10+ indispensable for the cell cycle start in a
      wild-type cell. After being transferred to a fresh medium at 36.5 degrees C, the
      multinucleate cells rapidly divided with aberrant nuclear segregation. Thus, cps8
      mutation allows cells to undergo mitosis without DNA replication at the
      restrictive temperature. The cps8 gene was mapped on the left arm of chromosome
      II closely linked to but distinct from cdc2 locus.

PMID- 8292391
TI  - [Rupture of posterior wall of the left ventricle after mitral valve prosthesis].
AB  - Rupture of the posterior wall of the left ventricle is a comparatively rare
      complication occurring after prosthesis of the mitral valve, but resulting in
      high mortality. There is a great diverse of opinions regarding the causes of this
      complication. The likely causes are surgical injury and the used method for
      prosthesis. The authors studied 9 patients with rupture of the posterior wall of
      the left ventricle following mitral prosthesis. In all patients the prosthesis
      was carried out by the routine procedure by dissecting the two mitral cusps with
      subvalvular structures. Two (22%) patients survived after defect plasty. The
      above surgical policy is the most effective to control bleeding and achieve a
      favourable result of correction of this complication.

PMID- 8292392
TI  - [Resection of posterior tibial veins with ligation of arteriovenous anastomosis
      in acute ischemia of the lower extremities].
AB  - The paper deals with the pathophysiological validation and assessment of the
      efficiency of a new low-traumatic operation aimed at decreasing the degree of
      injured extremity ischemia in patients with atherosclerosis obliterans and
      decompensation of peripheral circulation. The essence of the operation is to
      remove arteriovenous shunting into the shin. Eighteen patients were operated on,
      out of them only 5 underwent a subsequent amputation. It is concluded that this
      intervention is promising and indications for it are defined in this paper.

PMID- 8292393
TI  - [Long-term results of surgical treatment of patients with renovascular
      hypertension].
AB  - The paper analyzes the long-term results of surgical management of vasorenal
      hypertension in relation to the type of the reconstructive operation made. It
      provides data on the mortality rate of these patients in the late period and
      shows the ways of its reduction. The follow-up was from 5 to 25 years. The
      findings allow angiosurgeons to make the rational method for reconstructing the
      diseased renal artery clear.

PMID- 8292394
TI  - [Short and long-term results of non-standard revascularization of the lower
      extremities].
AB  - A total of 125 patients with unreconstructable Stages III and IV lower extremity
      arterial occlusions were treated by an unconventional procedure (Ilizarov's
      procedure). The patients underwent longitudinal osteotomy, then distraction of
      the obtained bone break for 31-36 days, followed by its fixation for 45-60 days.
      Additionally, lumbar sympathectomy and arterial reconstruction were performed in
      41 and 16 patients, respectively. During surgery bone fracture occurred in 2
      cases. After intervention, local infectious complications were observed in 16
      patients. A direct positive result was seen in 95 (76.0%) patients. In the long
      term period (mean 21.6 months later), a positive result was seen in 83 (94.2%) of
      88 examinees.

PMID- 8292395
TI  - [Radical surgical treatment of atrial flutter].
AB  - From January 1983 to May 1992 a total of 40 patients with a tachysystolic type of
      atrial flutter (AF) refractory to preventive antiarrhythmic therapy were examined
      and operated on. The obligatory stage of a preoperative examination was invasive
      phonoelectrocardiography. The effects of "entrainment" and adaptation of
      refractory periods of various portions of atria were estimated depending on the
      duration of a basic stimulation cycle. In inducing a AF paroxysm, the site of
      early A spike appearance was determined and endomyocardial mapping was performed.
      During intraoperative mapping, the data on low-amplitude and fragmented activity
      were processed by a computer. The sequence of the electric activation of the
      atria in AF was also determined. Twenty seven transthoracic operations were
      performed via extracorporeal circulation, 9 of them underwent laser or cryogenic
      isolation of the atrioventricular node, 4 laser photo ablation, 10
      cryodestruction of arrhythmogenic areas. Resection of 1/3 of the marginal crust,
      sinoatrial node with subsequent implantation of a pacemaker was made in 1 patient
      in the AA1 mode. Three patients underwent operation to create a labyrinth by J.
      Cox and a corridor by J. Quiraudon. The closed heart operations involved both
      transvenous electrodestruction of arrhythmogenic areas (5 patients) and
      destruction of the His bundle with developed complete block and pacemaker
      implantation in the VVI mode (8 patients). The best results of surgical treatment
      were obtained in young patients with idiopathic AF (Type 1), when the areas of
      fragmented and low-amplitude activity could be accurately determined.

PMID- 8292396
TI  - [Extravasal compression of celiac trunk: choice of adequate methods of
      correction].
AB  - The paper describes the clinical features, a scheme of pathogenesis and a
      classification of extravasal compressions of the celiac trunk in 106 patients who
      have undergone surgery. The scope of operations depended on the stage of the
      disease, in uncomplicated cases, decompression was carried out. In periarterial
      fibrosis it was supplemented by arteriolysis or changes of blood flow to the
      liver. At Stage IV reconstructive operations were performed and secondary
      complications were corrected. A total of 92.3% of excellent and good results were
      obtained, including 100% of clinical recoveries at Stages I-II, indicating the
      necessity of early surgical treatment.

PMID- 8292397
TI  - [Pathogenesis and immediate results of surgical treatment for spontaneous non
      specific pneumothorax].
AB  - The paper analyzes the follow-up of 301 patients with spontaneous nonspecific
      pneumothorax, out of them 103 (52.24%) underwent intraoperative intervention.
      Bullous emphysema as the most common cause of spontaneous nonspecific
      pneumothorax was revealed in 74 (71.84%) patients operated on. The paper also
      describes the pathogenesis of restricted bullous emphysema and the mechanism of
      occurrence of spontaneous pneumothorax. The most important etiological factors in
      the development of bullous changes are impaired blood supply in the pulmonary
      parenchyma and disturbed bronchial patency, which developed in the presence of
      various obstructive lung diseases. Most (75.72%) patients underwent atypical
      resection of changed portions of the lung with an YO-60 device in combination
      with parietal stepwise pleurectomy which prevents a further progression of
      pulmonary dystrophy and occurrences of relapses of spontaneous nonspecific
      pneumothorax.

PMID- 8292398
TI  - [Surgical treatment of complicated bullous pulmonary emphysema].
AB  - The paper provides the results of treating 118 patients aged 16 to 78 years who
      had complicate bullous emphysema. The most frequent complication was spontaneous
      pneumothorax (n = 107). Chronic respiratory failure was observed in 8 patients
      with bullous formations occupying 1/3-2/3 of the hemithorax volume. Two patients
      had recurrent hemoptysis. Eighty patients with spontaneous pneumothorax underwent
      thoracic operations: endoscopic bullectomy, endoscopic pleurodesis with MK-7 and
      MK-8 medical glues, endoscopic electro- and laser coagulation of pulmonary bullae
      through infrared gallium arsenide and argon lasers. Thoracotomy with marginal
      resection of the lung, bullectomy, parietal pleurectomy was performed in 29 (25%)
      patients. The paper shows indications and contraindications for endoscopic and
      surgical operations, methods for applying IGA laser for marginal resection of the
      lung, bullectomy, pleurectomy, endoscopic coagulation of the bullae,
      complications of endoscopic and surgical treatments.

PMID- 8292399
TI  - [Combined use of various laser radiations in thoracic surgery in experimental
      studies].
AB  - The impact of various types of low-intensive lasers (He-Ne, copper vapour,
      ultraviolet, infrared, infrared gallium arsenide) on healing of a wound made by
      CO2 laser at an output power of 25 W was studied in an experiment on 120 albino
      Wistar rats. It was found that a concurrent application of high- and low
      intensive lasers resulted in acceleration of reparative processes in the lung,
      stimulating the healing of laser-induced wounds. The infrared gallium arsenide
      laser was demonstrated to be the best tool in stimulating the healing process.

PMID- 8292400
TI  - [Treatment of postoperative complications after surgery for esophageal cancer and
      cancer of the cardioesophageal junction].
AB  - Out of 108 patients with gastric and cardiac cancer and surgical complications,
      49 were treated in the routine manner and 59 operatively. The immediate results
      were equal in either cases: 17 (34.7 +/- 6.8%) of 49 patients and 23 (39.0 +/-
      6.35%) of 59 patients died (r = 0.46). However, to compare the results of two
      therapeutical policies is impossible: the magnitude of pathological changes and
      the severity of the patients' condition is too incomparable before a decision is
      made which therapeutical policy is chosen. The largest number of repeated
      emergency operations (22 patients) was associated with impaired hermiticity of
      the gastrointestinal tract. The major causes of this abnormality is esophageal
      anastomotic suture incompetence (2.7%) and graft necrosis (1.0%). Impaired
      patency in various parts of the gastrointestinal tract occupies the second place
      in its incidence (20 patients) for which 19 repeated emergency surgical
      interventions were made. Postoperative bleeding requiring repeated emergency
      surgical intervention occurred in 0.5%; in all cases, the bleeding was
      intrathoracic, chylothorax was detected in 1 patient, mediastinitis without
      disintegrity of the digestive tube was also noted in 1 patient, pancreonecrosis
      was recorded in 2 cases. Due to the introduction of extensive lymph dissection
      into these operations in 1990, the frequency of complications increased up to
      2.1%.

PMID- 8292401
TI  - [Gastrojejunostomy in proximal resection of the stomach].
AB  - A new mode of forming an invaginational areflux esophagus-stomach-intestinal
      anastomosis was proposed. Seven patients were operated on by the proposed
      procedure. No cases of incompetence of anastomotic sutures were observed. The
      analysis of long-term outcomes suggests that there were no complications such as
      reflux-esophagitis and cicatricial strictures, which is accounted for by
      anatomical and surgical features of this mode of anastomosis.

PMID- 8292402
TI  - [Posttraumatic coronary fistula].

PMID- 8292403
TI  - [Rare benign tumor of the right atrium].

PMID- 8292404
TI  - [Mitral valve prosthesis reoperation for early prosthetic endocarditis with
      partial prosthesis displacement].

PMID- 8292405
TI  - [Successful correction of aortic left ventricular tunnel in a 2 year-old child].

PMID- 8292406
TI  - [Instrumental dilatation of the left coronary artery trunk in isolated subtotal
      stenosis].

PMID- 8292407
TI  - [Combination of rare pleural mesothelioma with the azygos vein lobe of the lung].

PMID- 8292408
TI  - [Use of the pediculated greater omentum to treat bronchial fistula after
      pneumonectomy].

PMID- 8292409
TI  - [Treatment of lung gangrene complicated with disseminated thoracic phlegmon].

PMID- 8292410
TI  - [A case of cancer development in tuberculoma].

PMID- 8292411
TI  - [Pulmonary sling in a patient with anomalous intrathoracic heart displacement
      (diagnosis and surgical treatment)].
AB  - The pulmonary sling is the origin of the left pulmonary artery from the right
      one, this is a rare abnormality giving a marked clinical picture. The paper
      presents a case of solely rare combination of the pulmonary of the pulmonary
      sling with abnormal cardiac placement--dextroversion. A three-year-old child
      underwent explorative thoracotomy for erroneously diagnosed mediastinal cyst. The
      thoracotomy revealed a suspected pulmonary sling. To make an accurate diagnosis,
      a comprehensive study (chest X-ray with esophageal contrasting,
      tracheobronchography, echocardiography, digital subtraction angiography) was
      performed. Echocardiography clearly showed the absence of bifurcation of the
      pulmonary trunk and the origin of the left pulmonary artery from the right one
      proved to be most informative, as evidenced by colour Doppler mapping. The paper
      deals with the specific features of surgical treatment of this pathology (the
      patient was successfully operated on through lateral sternotomy by using
      extracorporeal circulation). The good functional result of the operation was
      confirmed by echocardiography and angiography.

PMID- 8292412
TI  - Avoiding burnout in general practice.

PMID- 8292413
TI  - Exercise and health promotion.

PMID- 8292414
TI  - Does sleep disturbance predict depression in elderly people? A study in inner
      London.
AB  - Insomnia in elderly people has traditionally been regarded as inevitable and
      trivial. A longitudinal study was undertaken to examine the prevalence of sleep
      disturbance among elderly people in an inner London community and its association
      with demographic variables, depression, dementia and disability. Those aged 65
      years and over living at home were interviewed using a validated and reliable
      semi-structured interview schedule. A total of 705 people were interviewed in
      1987-88 and 524 were re-interviewed in 1990. Subjective sleep disturbance was
      found to be common (33% and 43%, respectively). Sleep disturbance was associated
      with being a woman, being unmarried, living alone, disability, and current and
      future depression, but not with dementia or older age. The best predictor of
      future depression in elderly people who were not depressed was current sleep
      disturbance. In the presence of current sleep disturbance, the traditional
      predictors of depression--being a woman, having a disability, being unmarried,
      living alone and being older--did not contribute further. This study has shown
      that sleep disorder is associated with pathology. Insomnia in elderly people
      requires assessment and this must be accompanied by the treatment of underlying
      disorders and monitoring of future health.

PMID- 8292415
TI  - Factors influencing the career choices of general practitioner trainees in North
      West Thames Regional Health Authority.
AB  - The aim of this study was to identify those factors influencing general
      practitioner trainees when choosing their future place of work, with particular
      reference to those issues that might be relevant to a choice of practice in inner
      London. A questionnaire was sent to the 90 trainees undertaking the final
      component of general practice training within North West Thames Regional Health
      Authority in May 1991. Seventy five doctors responded to the questionnaire, of
      whom 47 (63%) were women. Forty five per cent of women indicated that they wished
      to work part time, compared with 6% of the men. Only 21 trainees (28%) said that
      they would consider working in inner London, 36 (48%) stating that they would
      definitely not work in this location, with only nine (12%) indicating a
      willingness to work in a single handed practice and 21 (28%) in a two doctor
      practice. Specific factors identified as important when choosing a practice
      included a good working relationship with partners and staff, the presence of a
      practice nurse and practice manager, attached health authority staff,
      opportunities for postgraduate education, and good relationships with hospitals.
      Of the 800 practices in the north west Thames region, 62% are either one or two
      doctor practices, these being more prevalent in inner London areas where training
      practices are less common. Given the preferences expressed by trainees, future
      recruitment in inner London is likely to be more difficult than
      elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292416
TI  - Epilepsy: a general practice study of knowledge and attitudes among sufferers and
      non-sufferers.
AB  - The aim of this study was to examine epilepsy sufferers' attitudes to and
      knowledge of their condition, the effect of epilepsy on their lives and their
      views on the management they had received, and to compare knowledge and attitudes
      with those of a control group of non-sufferers. A questionnaire was completed by
      29 patients with epilepsy and 32 control group subjects from two general
      practices. It was found that people with epilepsy knew little more than those
      without epilepsy regarding the nature of the condition, its aetiology and seizure
      precipitants. Those with epilepsy were concerned about the seizures and the
      effect these had on various aspects of their lives, and were concerned about long
      term side effects of anti-epileptic medication. There were no significant
      differences between the two groups with respect to educational achievement,
      employment record and social activities. The findings are discussed and
      suggestions put forward for improving the care offered to epilepsy sufferers by
      both general practitioners and hospital clinics.

PMID- 8292417
TI  - Management of ophthalmic disease in general practice.
AB  - A study was undertaken to investigate the management of ophthalmic conditions in
      general practice in order to identify areas requiring education and training
      input. Management of patients with eye disease presenting to 17 Nottingham
      general practitioners was examined over a 12-month period. Of all patients
      registered with the participating doctors, 4% presented with eye problems,
      accounting for 1.5% of all general practice consultations. Children under five
      years of age had the highest consultation rates, female patients having higher
      consultation rates than male patients in all age groups. Infective conjunctivitis
      was responsible for 41% of consultations about eye problems and allergic
      conjunctivitis for a further 13%; 70% of consultations resulted in a
      prescription. Corticosteroids were prescribed in 3% of consultations for eye
      problems; this was considered inappropriate by the study ophthalmologist in over
      a third of these cases. Patients were referred for further management following
      16% of consultations. Thirty nine per cent of referrals to the hospital
      ophthalmic service were either to an eye casualty department or requested an
      urgent clinic appointment. While most eye problems are managed solely by general
      practitioners there is clearly a need for ophthalmic services that can rapidly
      provide a specialist opinion. However, most eye disease seen in general practice
      involves the external eye or anterior segment, and the diagnosis may be
      confidently made using basic ophthalmic history taking and examination skills
      with non-specialist equipment. The acquisition of these skills should be
      emphasized at undergraduate level and built upon in later years in postgraduate
      training.

PMID- 8292418
TI  - General practitioners' beliefs about their role in the prevention and treatment
      of accidents involving children.
AB  - This questionnaire survey set out to determine the perceptions of family doctors
      in north Staffordshire regarding their role in the prevention and treatment of
      childhood accidents. Of 277 doctors sent questionnaires, 207 (75%) replied. Only
      23% of respondents considered that they did enough child accident prevention
      work; lack of time was mentioned as a limiting factor by 66%. Child health
      surveillance clinics and home visits were considered by 60% and 59% of
      respondents, respectively, to be appropriate occasions on which to give
      prevention advice. However, only 12% of respondents frequently gave safety advice
      while visiting a child. Significantly more older general practitioners (over 44
      years) gave advice during a visit than younger doctors. Among doctors with a
      health visitor who was practice rather than geographically based significantly
      more gave advice on a home visit and discussed safety issues with their health
      visitors. Significantly more general practitioners in practices more than five
      miles from the nearest accident and emergency department offered to provide
      treatment for children following an accident than those in practices nearer to a
      hospital. Child accident prevention has recently been targeted as an important
      area for health promotion in primary care. However, this district based survey
      has identified a relatively low profile for the subject in the everyday
      activities of the general practitioner. The need for further research to
      determine the precise role of the family doctor in the prevention and treatment
      of children's accidents is highlighted.

PMID- 8292419
TI  - Demographic characteristics of general practitioners attending educational
      meetings.
AB  - There are many factors which influence general practitioners' behaviour with
      regard to attendance at education meetings. The demographic characteristics of
      general practitioners in the west of Scotland attending educational meetings were
      studied over a two year period. A total of 1672 doctors had attended sufficient
      sessions to claim their postgraduate education allowance and of these 1551 (93%)
      responded to the questionnaire. Overall attendance at meetings did not vary
      between age groups, but older doctors (those born before 1935) attended the
      highest mean number of education sessions on disease management and the lowest
      mean number on service management and health promotion. Doctors in rural areas
      attended fewer meetings than those in urban areas with the largest difference in
      the disease management category. Doctors from smaller practices attended
      significantly fewer sessions on service management than those from larger
      practices. There was no difference between sexes regarding the mean total number
      of education sessions attended but men attended significantly more sessions on
      service management and women attended more on health promotion. Full-time doctors
      attended more service management sessions than part-time doctors. Those who were
      widowed or divorced attended fewer sessions in total, the differences being
      greatest in service management and health promotion. Multiple regression analysis
      showed that location of practice, whether working full time or part time and
      marital status had a small but statistically significant bearing on overall
      attendance at meetings. Although the differences are small, these factors should
      be noted by education providers, negotiators and government.

PMID- 8292420
TI  - Do general practitioners and general psychiatrists want to look after drug
      misusers? Evaluation of a non-specialist treatment policy.
AB  - A new means of monitoring drug misuse which was developed in the north west of
      England, but is now widely used throughout the United Kingdom, is described and
      evaluated. Report forms which had been specially designed and ensured the
      anonymity of drug misusers were widely distributed among doctors and non-medical
      health workers who may have had contact with drug misusers. The forms were
      returned post-free to a centre where they were entered on a customized drug
      misuse database. There were 2127 reports from the north west of England
      (population 3.99 million) relating to 1792 individuals over a 15-month period.
      However, despite intensive promotion of the project among doctors, the number of
      reports from doctors remained virtually unchanged over the 15 months despite a
      33% increase in the overall number of reports. When the reports from three health
      districts, selected so as to be representative of the region demographically
      (total population 658,500, population aged 15-44 years 292,200), were considered
      there was a substantial fall (70%) in reports from general practitioners which
      was considerably greater than the 2% fall in all reports. In a linked study all
      the psychiatrists, 30% of probation officers and a one in six sample of general
      practitioners from the three selected health districts were approached for
      interview at the beginning of the 15-month period and again a year later. This
      structured enquiry about caseloads, treatment, and attitudes also revealed a fall
      in the number of drug misusers attended by general practitioners and general
      psychiatrists and a reduction in the services provided for them by general
      practitioners.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292421
TI  - Holistic medicine or the humane doctor?
AB  - The holistic doctor is sometimes proposed as an ideal. However, holism involves
      an expansion of medical categories to encompass most of 'normal' life as well as
      sickness. The humane doctor is suggested as a better ideal. He or she is wise,
      compassionate and liberally educated; and knows that there is more to life than
      medicine-both for doctors and their patients. Humane practice is promoted by a
      broad and rigorous education but inhibited by excessive busyness and pressurized
      conditions of work. This has implications for medical training and work
      practices.

PMID- 8292422
TI  - Skin biopsies by GPs.

PMID- 8292423
TI  - Oculokinetic perimetry.

PMID- 8292424
TI  - GP trainees.

PMID- 8292425
TI  - List sizes.

PMID- 8292426
TI  - Refugees' health needs.

PMID- 8292427
TI  - Health care for homeless people.

PMID- 8292428
TI  - Endometrial sampling.

PMID- 8292429
TI  - Response rates in general practice studies.

PMID- 8292430
TI  - Diabetic non-attenders.

PMID- 8292431
TI  - [The prognostic value of the endoscopic signs in the recurrence of peptic ulcer
      hemorrhage].
AB  - The endoscopic signs of hemorrhage in bleeding peptic ulcers are considered as
      prognostic factors for rebleeding and mortality. The value of these signs has
      been examined in several studies of patients with known high risk factors. In
      this survey, we studied the prognostic value of the endoscopic signs of
      hemorrhage in bleeding peptic ulcer in a group of patients without clinical risk
      factors such as age > 60 years, concomitant malignancy or respiratory and heart
      disease. Endoscopic findings were examined in fifty patients without rebleeding
      (group I) and twenty five with rebleeding (group II). Endoscopic findings results
      were spurting arterial bleeding in 9.3% of the cases, oozing hemorrhage in 17.3%
      of the cases, visible vessel in 9.3% of the cases, and adherent clot in 82.3% of
      the cases. In 9.3% of the cases endoscopic findings were negative. No statistical
      differences were found in the endoscopic signs among the two groups. The visible
      vessel and the spurting arterial bleeding cases presented in more than 50% of the
      rebleeding, (visible vessel and spurting arterial 57.1%). Oozing hemorrhage and
      the adherent clot were present in 30% of the cases. The endoscopic signs of
      bleeding can assist in choosing the group of patients with prospective high risk
      of rebleeding and possible candidates for the new treatment of endoscopic
      hemostatic therapy.

PMID- 8292432
TI  - [The defecation habits in a normal working population].
AB  - We have studied the bowel habits of a theoretically normal working population to
      know the range defecation patterns, characteristics and main factors that may
      influence it. We have designed a questionnaire composed of 80 questions and
      distributed to 837 people. Answers, were evaluated in 414 cases (187 men and 227
      women), with a median age of 33 years (range 20-64 years). The average number of
      stools was 7.1 +/- 3.3 per week and in 62.4% of subjects they were between the
      range of 5 and 8. Bowel movements were less frequent in women than in men, and
      the same finding was seen about self-reported constipation; nevertheless there
      were no differences in regard to age. Laxatives were used regularly by 11.3%, and
      36% referred straining at stool at least 25% of the time and 8.3% referred
      straining for loose stools. Alternating bowel function presented in 19.4% and
      functional abdominal pain in 28% with a female predominance. Faecal incontinence
      occurred in 6.8% of population; an important prevalence. We also analyse
      variables such as diet influence, physical activity, obstetrical, gynaecological
      and psychosocial factors. Although this survey has revealed that a normal bowel
      function is very variable, only a 7.5% of the subjects, consulted a doctor for
      bowel complaints.

PMID- 8292433
TI  - [Synchronous colonic and rectal carcinomas].
AB  - We present a retrospective study of 360 patients with surgically treated
      colorectal neoplasm between 1982 and 1990, in order to determine the incidence of
      synchronous colorectal carcinomas; and to analyze diagnosis procedures, detection
      time, pathology and treatment strategies. The incidence of synchronous carcinomas
      was 5.5% (20 cases). Only 30% of them were diagnosed preoperatively, and up to
      40% were discovered in the pathological examination. In 2 patients 3 synchronous
      tumors were well found. All the synchronous neoplasms were differentiated, 65% of
      them were Dukes stage A. Synchronous colorectal polyps were found in 80% of
      patients. Complete exploration of the colon preoperatively by a routine pan
      colonoscopy is recommended. In regard to the treatment of patients with
      synchronous colorectal carcinomas, partial colectomies are indicated as long as
      oncological criteria are followed, and the colon had been fully explored.

PMID- 8292434
TI  - [Hemorrhoidectomy: conventional or by Nd:Yag contact laser? A prospective and
      randomized study].
AB  - OBJECTIVE: To assess whether hemorrhoidectomy done with the Nd:YAG laser was
      associated with less pain or fewer complications and sequels than with
      conventional surgery. DESIGN: A prospective comparative, randomized study.
      PATIENTS: Over a period of six months, a total of 35 consecutive patients, 13
      females and 22 males, with symptomatic hemorrhoidal disease requiring surgery,
      were alternatively randomized to either laser hemorrhoidectomy (17 patients) or
      surgery (18 patients). The type of disease and the number of affected and treated
      hemorrhoids were prospectively recorded in each patient. Patients were monitored
      prospectively for postoperative complications, pain (assessed daily for five days
      using a standard 10 mm. linear analogue scale), wound healing, time until full
      recovery and sequelae 6 moths later. RESULTS: These two groups were well matched.
      No differences were seen between laser and non-laser groups for postoperative
      complications. Linear analogue pain scores were not significantly different
      between the two groups at any stage after operation. Healing time was longer in
      laser group. Two few patients returned at 6 months for rectoscopy for any
      meaningful conclusion to be drawn. CONCLUSIONS: This study has failed to confirm
      any reduction in postoperative pain, complications, or healing time laser when
      performing a hemorrhoidectomy.

PMID- 8292435
TI  - [The incidence and chronology of the appearance of anti-HCV in posttransfusional
      non-A, non-B hepatitis].

PMID- 8292436
TI  - Frequency and chronology of occurrence of anti-HCV in non-A non-B post
      transfusional hepatitis.
AB  - OBJECTIVE: Studying the frequency and timing of the appearance of the virus C
      antibody. PATIENTS: We studied serum samples of 57 patients whom developed post
      transfusional non-A non-B hepatitis. 34 males, and mean age was 47.56 +/- 13.45
      years. Initially anti-HVC was detected by ELISA, and the test was repeated on the
      last negative sample and the first two positive ones of each patient. RIBA-I and
      2nd generation ELISA were performed on these same samples. HCV polymerase chain
      reaction was performed in 5 seronegative patients by the other techniques.
      RESULTS: Fifty patients (87.5%) seroconverted to anti-HCV; 26 (52%) within 30
      days after the onset of the disease (11 during incubation period); and, 24 (48%)
      seroconverted after the first month of the disease. Anti-HCV negative patients
      had lower transaminase levels. Twenty six (52%) of the 50 patients showing
      seroconversion developed a chronic hepatitis, while this occurred in two (28.5%)
      of the seven seronegative patients (this difference was not statistically
      significant). Determination of HCV-RNA by polymerase chain reaction, performed
      (eight years after the onset of the disease) in 4 of the five seronegative
      patients by ELISA and RIBA techniques, was negative. Nowadays one of them is anti
      HCV and HCV-PCR positive and sustain normal transaminases values. CONCLUSIONS:
      87.5% of post-transfusional non-A non-B hepatitis seroconverted during the follow
      up. 26 (52%) showed this within 30 days after the onset of their disease; of this
      group, 11 became seropositive before their ALT values rose. Nowadays in all
      patients (except one) initially seronegative, in which polymerase chain reaction
      was performed, negative serology results persist. There were no clinical and
      evolution differences between the groups.

PMID- 8292437
TI  - [Extrahepatic biliary lesions in abdominal traumatism].
AB  - The extrahepatic biliary tree traumatisms are rare and hard to diagnose; 15 of
      864 patients with surgery treatment for abdominal trauma for over 19 years (1974
      1992) were studied retrospectively. Twelve blunt abdominal traumas (9 traffic
      accident and 3 falls down) and 3 open traumas (stabbing in two and gunshot wounds
      in one case). Eleven had gallbladder injury, two gallbladder and biliary duct and
      two exclusively biliary duct. Only one case was an isolated lesion, in the rest
      of cases, intra or extra abdominal lesions, occasionally both, were seen. The
      diagnostic method, associated lesions, morbi-mortality are reviewed. Surgical
      treatment was cholecystectomy for gallbladder injury and direct suture with T
      tube (Kehr) for biliary duct injury.

PMID- 8292438
TI  - [The epidemiological and etiopathogenic aspects of chronic alcoholic
      pancreatitis].

PMID- 8292439
TI  - [The ultrashort bowel syndrome: the surgical treatment of an exceptional case].
AB  - An exceptional case of a 16-year-old boy who accidentally lost all of the small
      bowel (except the proximal 5 cm. of jejunum), and also 10 cm of transverse colon
      and a small part of the middle and upper rectum, is presented. After suffering
      severe medical complications derived from prolonged and uninterrupted total
      parenteral nutrition for more than one year, with no oral intake except fluids,
      the patient underwent intestinal lengthening of all the residual bowel up to the
      sigmoid colon, with antiperistaltic anastomosis and sigmoid J pouch with myotomy.
      Several months after the operation the patient returned to his normal activities
      and is fed with a free-diet, complemented or not with nocturnal enteral and
      parenteral feeding, depending on the circumstances and weight variations.
      Lengthening of the large bowel together with the rest of surgical gestures here
      performed has not been published previously.

PMID- 8292440
TI  - [Multiple hepatic-splenic abscesses. A favorable result with antibiotic
      treatment].
AB  - The authors report a case of multiple and spleen pyogenic abscesses caused by
      Peptostreptococcus spp., in a patient who recently underwent laparotomy due to
      duodenal perforation. He was successfully treated by means of intensive and
      extended antibiotherapy. We would like to stress the importance of an early and
      etiological diagnosis performed by percutaneous puncture and bacteriological
      study, in order to start a selective antibiotherapy. Other therapeutical
      possibilities are discussed.

PMID- 8292442
TI  - [Droxicam and severe cholestasis].

PMID- 8292441
TI  - [Hepatocarcinoma: a rare form of presentation].
AB  - A case of acute abdomen presenting with pain in the right upper abdomen, pyrexia
      and leukocytosis is presented. At laparotomy, hepatocarcinoma with necrosis and
      associated acute cholecystitis was found. This is apparently an unusual report of
      hepatocarcinoma presenting as acute cholecystitis.

PMID- 8292443
TI  - [Droxicam-induced hepatitis: a report of 2 cases].

PMID- 8292444
TI  - [The Dubin-Johnson syndrome and cholelithiasis].

PMID- 8292445
TI  - Rationale for the rational development of new cardiac imaging agents.
AB  - There are several prerequisites for the development of new diagnostic
      cardiovascular radiopharmaceuticals. Agents which are proposed for clinical use
      must offer significant advantages in one or more of the following categories: I)
      Radiopharmacy [dosimetry, dose preparation, dose availability]; II) Imaging
      characteristics [spatial and temporal resolution, radiotracer biokinetics,
      patient throughput and acquisition protocols]; and III) Measurement of a
      previously unmeasurable physiologic or pharmacologic event [metabolic pathways,
      receptors, neural pathways, preclinical disease]. Technetium-99m-based
      radiopharmaceuticals are particularly attractive, in view of their excellent
      characteristics for imaging with the Anger gamma camera. In addition, the
      increasing use of tomographic imaging and reconstruction techniques has magnified
      the importance of developing radiotracers with minimal soft tissue attenuation
      effects. Technetium-99m and positron emitting radioisotopes offer this advantage.
      A wide choice of biologically and pharmacologically relevant ligands are
      available for complexing with these radiotracers. The clinical studies are
      underway in order to validate these new agents, and to determine their value in
      the modern practice of nuclear medicine. Technetium-99m sestamibi is just one
      example of a novel radiotracer with improved imaging characteristics that has
      undergone careful pre-clinical and clinical testing, and which has emerged as a
      useful diagnostic imaging agent. Future studies should be directed towards the
      development of tracers with well-defined biokinetic characteristics, which are
      advantageous for tomographic imaging. The future applications of tracer imaging
      techniques for the pre-clinical diagnosis of cardiovascular, oncologic and other
      medical conditions are significant and are expanding.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8292446
TI  - The value of Tc-99m Nanocolloid scintigraphy in the evaluation of infected total
      hip arthroplasties.
AB  - The early diagnosis of loosening is very important, since it provides a chance to
      protect the bone structure by means of a good postrevision outcome. Although the
      delayed stage of infected loosenings can easily be detected by clinical
      presentations, significant laboratory data and plain X-rays, diagnosis becomes a
      problem in the early stage. In this study the value of Tc-99m Nanocolloid (NCol)
      scintigraphy in the diagnosis of infected loosenings was evaluated in 28 patients
      with painful total hip arthroplasty and 10 controls without any complaint after
      total hip arthroplasty, by comparing this method with laboratory data, plain X
      rays and 3-phase Tc-99m methylene diphosphonate (MDP) scintigraphy. Tc-99m NCol
      scintigraphy was found out to be a very valuable method with 100% sensitivity,
      84% specificity in the diagnosis of infected prosthesis and it was superior to
      laboratory data, plain X-rays and 3-phase Tc-99m MDP scintigraphy, but requires
      to be evaluated in conjunction with plain X-rays for more information and in
      order to prevent false positive results.

PMID- 8292447
TI  - Usefulness of bone SPECT of the cervical spine: with special reference to
      separate visualization of the trachea and thyroid cartilage.
AB  - We applied bone SPECT for the examination of the cervical spine. A three-head
      rotating gamma camera SPECT system was employed for this study. The SPECT image
      disclosed 42.7% of abnormal accumulations in the skeleton not seen with planar
      imagings. SPECT could separately visualize the trachea and thyroid cartilage and
      also provided interpretation of abnormality in the anterior part of the vertebral
      body being difficult with planar imagings only. The trachea cartilage was seen in
      55.4% and the thyroid cartilage was seen in 47.3% of patients with anterior neck
      density in planar imagings. SPECT clarified that marked cervical curvature and
      diffuse high uptake by the skeleton might cause high intensity of the anterior
      neck in planar imagings in the case of non-pathological change. We concluded that
      bone SPECT is a useful diagnostic tool in detecting occult lesion in the skeleton
      and to rule out extraskeletal accumulations in examination of the cervical spine.

PMID- 8292448
TI  - Assessment of area at risk and efficacy of treatment in patients with acute
      coronary syndrome using 99mTc tetrofosmin imaging in humans.
AB  - The determination of the myocardium at risk before intervention and the change in
      that region after intervention constitute a promising measurement tool for the
      assessment of acute therapy. A new 99mTc labeled myocardial blood flow tracer,
      99mTc tetrofosmin, is expected to enable the evaluation of myocardium at risk
      because of the absence of redistribution. This preliminary study was performed in
      9 patients with acute coronary syndrome (4 unstable angina and 5 acute myocardial
      infarction) to investigate whether recovery of perfusion by tetrofosmin imaging
      parallels mechanical improvement. Tetrofosmin imaging was performed acutely and 3
      30 days later. Visual analysis of defect severity was assessed in both studies.
      Segments with improvement in perfusion were accompanied by significant wall
      motion recovery compared with normal and unimproved segments (delta WMI: normal
      segments 0.40 +/- 0.67, improved segments 1.79 +/- 0.68, unimproved segments 
      0.15 +/- 0.16, p < 0.01 for improved segments compared with other groups),
      suggesting the efficacy of this tracer for the assessment of the acute therapy.
      These data suggest that 99mTc tetrofosmin imaging is a useful method for the
      assessment of the myocardial area at risk and the efficacy of acute therapy in
      acute myocardial infarction and unstable angina.

PMID- 8292449
TI  - Basic evaluation of 67Ga labeled digoxin derivative as a metal-labeled
      bifunctional radiopharmaceutical.
AB  - To develop metal-labeled digoxin radiopharmaceuticals with affinity with anti
      digoxin antibody as well as Na+,K(+)-ATPase, a digoxin derivative conjugated with
      deferoxamine was synthesized. The derivative had a high binding affinity with
      67Ga at deferoxamine introduced to the terminal sugar ring of digoxin. The 67Ga
      labeled digoxin derivative showed enough in vitro binding affinity and
      selectivity to anti-digoxin antibody as well as Na+,K(+)-ATPase. The 67Ga labeled
      digoxin derivative is considered to be a potential metal-labeled bifunctional
      radiopharmaceutical for digoxin RIA as well as myocardial Na+,K(+)-ATPase
      imaging.

PMID- 8292450
TI  - Quantification of human splenic blood flow (quantitative measurement of splenic
      blood flow with H2(15)O and a dynamic state method: 1).
AB  - Positron emission tomography (PET) by means of a dynamic state method and H2(15)O
      was performed to quantify splenic blood flow in 20 patients who had no hepatic
      functional disorders. Non-linear regression analysis was applied to determine
      splenic blood flow. In calculating arterial input function for the spleen, our
      original exponential method was used to facilitate computerization. Mean splenic
      blood flow per 100 g of spleen (SBF) was 168.0 ml/min/100 g with a standard error
      (SE) of 12.4 ml/min. The mean spleen-blood partition coefficient for water (rho)
      was 0.767 with a SE of 0.020. Significant correlations were noted between the
      values for SBF obtained by the exponential method and linear method in which
      individual increasing values for arterial 15O concentration were used
      rectilinearly (r = 0.96, p < 0.005) and also between the values for rho obtained
      by the two methods (r = 0.95, p < 0.005). In order to validate the application of
      a one compartment model to an organ with a large blood volume such as the spleen,
      a further experiment was performed with a water flow model simulating splenic
      circulation. We succeeded in quantifying regional splenic blood flow by PET. It
      was thought that the quantification of splenic blood flow by our method would be
      beneficial in the study of splenic circulation, which is expected to be altered
      under conditions of portal hypertension, liver dysfunction and shock, etc.

PMID- 8292451
TI  - Relationship between liver function and splenic blood flow (quantitative
      measurement of splenic blood flow with H2(15)O and a dynamic state method: 2).
AB  - We measured splenic blood flow in 55 patients by means of quantitative splenic
      positron emission tomography (PET), a novel, dynamic state method with H2(15)O as
      a tracer. Twenty-four of the 55 patients suffered from liver cirrhosis (LC), 25
      showed no evidence of cirrhosis (NR) and 6 patients were diagnosed as having
      chronic hepatitis (CH). Splenic blood flow per 100 g weight of the spleen (SBF)
      was significantly correlated with splenic volume (r = -0.39, p < 0.005). The
      indocyanine green retention test at 15 min (r = -0.39, p < 0.005) and the
      hepaplastin test (r = 0.37, p < 0.025) also correlated significantly with SBF.
      The means and 95% confidence intervals for the LC, CH, and NR groups were 117.5
      ml/min/100 g (96.6-138.4), 102.5 ml/min/100 g (60.6-144.4), and 160.3 ml/min/100
      g (139.8-180.8), respectively. The differences in SBF between these 3 groups were
      significant (p < 0.01). We conclude that regional splenic blood flow is not
      proportionate to splenic volume, although the splenic volume does increase with
      the progressive chronic changes observed in hepatic diseases.

PMID- 8292452
TI  - Reassessment of quantitative thallium-201 brain SPECT for miscellaneous brain
      tumors.
AB  - In order to reassess the value of quantitative thallium-201 brain SPECT in the
      differentiation of miscellaneous brain tumors, we studied a total of 89 patients-
      35 pre-operative patients suspected of having a brain tumor and 54 post-operative
      patients with a brain tumor. We came to the conclusion that quantitative Tl-201
      brain SPECT was very useful in discriminating cerebral radiation necrosis from
      recurrent tumor, estimating residual tumor burden, and detecting tumor regrowth
      earlier in postoperative patients. In preoperative patients, however, Tl-201
      SPECT cannot be used effectively to differentiate glioma from other intracranial
      tumors, although intense uptake of Tl-201 may provide evidence of glioblastoma or
      a hypervascular lesion.

PMID- 8292453
TI  - Bile leakage after laparoscopic cholecystectomy demonstrated with 99mTc-PMT
      hepatobiliary scintigraphy.
AB  - A 41-year-old woman underwent laparoscopic cholecystectomy for the treatment of
      gallstone and adenomyomatosis. One month after laparoscopic cholecystectomy,
      hepatobiliary scintigraphy was performed with 99mTc-Sn-N-pyridoxyl-5
      methyltryptophan (PMT) to evaluate the presence of a bile leak and/or other
      complication. A biliary extravasation was noted in the left upper quadrant within
      60 minutes. At five hours post injection, a progressive accumulation of 99mTc-PMT
      was noted in the lesser sac, the right and left paracolic gutter and in the pouch
      of Douglas. A diagnosis of biliary leakage was made. The patient underwent
      exploratory laparotomy to repair the leak from the cystic duct stump.

PMID- 8292454
TI  - Demonstration of primary tracheobronchial amyloidosis by 99mTc-HMDP bone SPECT.
AB  - A case of primary tracheobronchial amyloidosis is reported. A 61-year-old man
      presented with a 2-year history of intermittent hemoptysis. Chest X-ray and CT
      scanning showed tracheobronchial thickening. Bronchoscopic examination revealed
      diffuse tracheobronchial narrowing, and tracheobronchial biopsy detected amyloid
      deposits. Both 99mTc-HMDP planar and SPECT images were obtained in this patient.
      Coronal SPECT images revealed more precisely that the activity was not in the
      thoracic cage but in the bilateral hilar region. Localization of the amyloid
      deposits could be better determined on SPECT images than on planar images.

PMID- 8292455
TI  - A patient with cardiac amyloidosis presenting a rapid increase in technetium-99m
      hydroxymethylene diphosphonate accumulation.
AB  - We assessed the changes in cardiac condition in a patient with cardiac
      amyloidosis, by means of dual nuclei single photon emission computed tomographic
      (SPECT) images with technetium-99m-hydroxymethylene diphosphonate (99mTc-HMDP)
      and thallium-201 (201Tl). Dual SPECT showed a marked increase in myocardial 99mTc
      HMDP accumulation along with deterioration of symptoms and signs, while 201Tl
      scintigraphy remained almost unchanged.

PMID- 8292456
TI  - Colloid liver SPECT of hepatic alveolar echinococcosis.
AB  - Seventy-one-year-old man had a liver mass. He lived in Hokkaido, where there is
      an epidemic of hydatic disease. Abdominal US image showed an echogenic mass. CT
      revealed a low density mass with an unclear margin. A 99mTc-Sulfur colloid liver
      SPECT study was performed to detect the liver mass. The SPECT scan was done after
      intravenous administration of 5 mCi of 99mTc-sulfur colloid, and it revealed a
      lack of uptake in the liver mass. The liver SPECT findings were correlated with
      subsequent CT and US imaging. Echo-guided biopsy showed a PAS-positive cuticle
      layer of echinococcosis in the necrotic tissue. This is the first report of a
      case of detection of hepatic alveolar echinococcosis by means of a colloid liver
      SPECT imaging procedure.

PMID- 8292457
TI  - Increased bone marrow uptake on Tc-99m DMSA scintigraphy in a patient with renal
      osteodystrophy.
AB  - A 16-year-old male patient was evaluated with Tc-99m Diethylenetriamine
      pentaacetic acid (DTPA) and Tc-99m 2-3 Dimercaptosuccinic acid (DMSA)
      scintigraphy for renal failure secondary to renal calculi. The uptake in the
      renal cortex was significantly decreased both on DMSA and DTPA studies. Uptake
      calculation on DMSA scintigraphy in the kidneys disclosed values of less than 5%.
      The activity in the liver and bone was significantly increased. A bone scan
      performed with Tc-99m methylene diphosphonate (MDP) revealed increased bone
      uptake with decreased soft tissue activity. Findings on bone scan were compatible
      with super scan, most likely due to renal osteodystrophy. This case illustrates
      the altered biodistribution of Tc-99m DMSA and a shift of the radiopharmaceutical
      to the bone marrow which is not likely related to colloid formation due to
      changes in mineral balance in patients with renal failure.

PMID- 8292458
TI  - The synergistic effects of interleukin 2 and interleukin 7 on the proliferation
      and autologous tumor cell lysis of tumor-associated lymphocytes.
AB  - Interleukin-7 (IL-7) has an ability to stimulate the proliferation of pre-B
      cells. It has been shown that IL-7 can also activate T lymphocytes. We here
      demonstrate that IL-7 in combination with interleukin-2 (IL-2) can drive cell
      proliferation and enhance the autologous tumor cell lysis by peripheral blood
      mononuclear cells (PBMC) and autologous mixed lymphocyte tumor cell culture
      (MLTC)-derived effector cells (MLTC cells). These synergistic effects of IL-2 and
      IL-7 on the proliferation and the augmentation of autologous tumor cell lysis
      were found for both effector cells. These effects were inhibited by neutralizing
      antibodies to IL-2 or IL-7, and by a combination of both antibodies,
      significantly. In terms of phenotypical expression, CD3 positive cells comprised
      the vast majority of MLTC cells after culture in medium containing IL-2 and IL-7
      with an increase of IL-2 receptor positive cells.

PMID- 8292459
TI  - Locoregional immunotherapy of head and neck cancers utilizing allogeneic spleen
      cells--a report of 2 cases.
AB  - Frozen-stored human spleen cells (SC) cultured with streptococcus preparation OK
      432 acquired direct cytotoxicity to autologous as well as allogeneic tumor cells.
      The activated cells started to produce cytocidal cytokine TGIF, which is distinct
      from previously known cytokines. We examined the possibility of allogeneic
      adoptive immunotherapy (AIT) using these OK-432-stimulated spleen cells (OK-SC)
      in two cancer patients. Rapid necrosis of cancer tissue and remarkable decreases
      of tumor markers in tumor effusion were observed. There were no severe side
      effects.

PMID- 8292460
TI  - Activation of peritoneal macrophages in patients with gynecological malignancies
      by sizofiran and recombinant interferon-gamma.
AB  - We investigated the influence of the combined use of sizofiran, a beta-1,3-glucan
      and a recombinant interferon-gamma (rIFN-gamma) upon biological activities of
      peritoneal macrophages (M phi). The number of peritoneal M phi and the production
      of cytokines (interleukin-1 beta, interferon-gamma and tumor necrosis factor) was
      increased by the combined treatment. Fully activated peritoneal M phi based on
      the increased number of elongated pseudopods were observed by electromicroscope.
      Sizofiran seems to assure a sufficient supply of M phi to kill tumor cells in the
      peritoneal cavity and co-administered rIFN-gamma seems to directly stimulate the
      accumulated M phi in addition to its direct cytotoxicity against tumor cells.
      This combination therapy may be a step to the prevention of the recurrence of
      gynecological malignancies including ovarian cancer, after a negative second-look
      laparotomy.

PMID- 8292461
TI  - Pharmacokinetics of an HIV-1 gp120-specific chimeric antibody in patients with
      HIV-1 disease.
AB  - The pharmacokinetics of mouse V/human C (gamma 1, kappa) chimeric monoclonal
      antibody CGP 47 439 specific for the principal neutralizing determinant of human
      immunodeficiency virus type 1 (HIV-1) was studied in patients with stage IV HIV-1
      disease in an open-labeled phase I/IIA trial. Twelve male patients were enrolled
      and nine completed the study. Patients were divided into three groups according
      to the extent of CGP 47 439 to bind to gp120 from their viral isolates:
      undetectable for group 1, modestly reactive for group 2, and strongly reactive
      for group 3. A first dose of 1, 10, or 25 mg was administered by intravenous
      infusion to group 1, group 2 and group 3 patients, respectively. The patients
      then received seven doses of 50, 100, or 200 mg, respectively, every three weeks.
      CGP 47 439 serum concentrations were determined by an ELISA using monoclonal
      antibody AB19-4 specific for the idiotope of CGP 47 439. Half an hour after
      infusion only 25.5-36.1% of the administered antibody was found in the serum,
      reflecting its rapid distribution in the extravascular space and possibly binding
      to gp120 antigen in some of the patients. The terminal elimination half-life
      (T1/2) was 16.2 days in group 1 patients, 9.7 days in group 2 and in group 3
      patients 7.5 days and 9.1 days. An antibody response to CGP 47 439 was not a
      factor in determining elimination rates, because only very low and transient
      responses were found in three patients. These results suggest that the reactivity
      of CGP 47 439 with HIV-1 gp120 contributed to its elimination in HIV-1 infected
      patients.

PMID- 8292462
TI  - Enhancement of anti-tumor activity of recombinant interleukin-2 (rIL-2) by
      immunocomplexing with a monoclonal antibody against rIL-2.
AB  - We have investigated biological properties of an immune complex of recombinant
      interleukin-2 (rIL-2) and a monoclonal antibody against rIL-2 in mice for
      induction of killer cells and for anti-tumor activity. We have also examined the
      clearance of subcutaneously-injected immune complex in mice and compared it with
      that of rIL-2 alone. Plasma rIL-2 levels were sustained longer in mice given the
      immune complex than in mice given rIL-2 alone at a dose of 10 micrograms/mouse,
      and they were detectable even at 24 hours after the administration of the immune
      complex, while they fell to undetectable levels by 6 hours after the
      administration of rIL-2 alone. A more significant portion of rIL-2 was detected
      in lymph nodes after subcutaneous injection of the immune complex than that of
      rIL-2 alone. Splenic lymphocytes from mice given the immune complex demonstrated
      a higher killer cell activity against YAC-1 cells than those from mice given rIL
      2 alone. The immune complex also exerted more significant anti-tumor effect in a
      dose-dependent manner in Meth-A fibrosarcoma-bearing mice than rIL-2 alone. Our
      results indicate that immunocomplexing of rIL-2 with an antibody against rIL-2
      provides a useful tool as the drug delivery system for cancer therapy using rIL
      2.

PMID- 8292463
TI  - Free at the point of entry?

PMID- 8292464
TI  - HIV and opportunistic infections: which makes the heart vulnerable?

PMID- 8292465
TI  - The incidence of first-dose hypotension with quinapril in patients with mild to
      moderate hypertension.
AB  - A total of 2242 patients with mild to moderate hypertension (diastolic pressure
      95-120 mmHg) were randomised on a double-blind basis to receive a single dose of
      placebo, 5 mg quinapril or 10 mg quinapril. Patients were identified who: (a) met
      the blood pressure (BP) criteria for first-dose hypotension (sitting or standing
      systolic BP < 100 mmHg, or a fall in systolic BP > or = 20 mmHg on standing); (b)
      had symptoms suggestive of hypotension; and (c) met the BP criteria and had
      symptoms. In all three classifications there were no statistically significant
      differences between the incidences in placebo and combined active treatment
      groups, or between those in the two quinapril groups. No associated serious
      adverse events were reported. In the low-risk population studied, it would appear
      that the incidence of first-dose hypotension with quinapril is similar to placebo
      and is not dose-related.

PMID- 8292466
TI  - A multicentre study of the safety and efficacy of amlodipine in mild to moderate
      hypertension.
AB  - An open, non-comparative study of 10 weeks' duration was conducted in general
      practice to assess the safety of amlodipine in patients with mild to moderate
      hypertension. Of the 5352 patients entering the study, 5135 received amlodipine;
      4621 patients (90%) with a mean age of 58.2 years completed the study.
      Normalisation of blood pressure was achieved in over 80% of patients with a mean
      reduction of 21/15 mmHg. The mean final dose of amlodipine was 6.8 mg/day.
      Adverse experiences possibly related to amlodipine were reported by 19.3% of
      patients, and overall adverse events led to withdrawal in 6.7% of patients. The
      most common reported side-effect was oedema. The frequency of headache was almost
      identical in older and younger patients and oedema, flushing and dizziness were
      seen only slightly more often in elderly patients. Ninety per cent of patients
      were considered by their GP to have shown excellent or good toleration of
      therapy. Over 85% of patients elected to continue on amlodipine therapy after
      completion of the study.

PMID- 8292467
TI  - Management of NSAIDs-related dyspepsia in the community.
AB  - Little is known about how non-steroidal anti-inflammatory drugs (NSAIDs)-related
      dyspepsia is managed in general practice. A survey was conducted to ascertain the
      preferred methods of investigation and management of NSAIDs-related dyspepsia by
      GPs in the Leeds district in the summer of 1992. A total of 261/300 (87%) replied
      to the questionnaire. Most (87%) GPs discontinued NSAIDs, and 12% changed the
      drug. Only 42 (16%) suggested endoscopy.

PMID- 8292468
TI  - The diagnostic potential of some routine laboratory tests. off.
AB  - The potential was tested of white blood cell count (WBC), haemoglobin
      concentration (Hb) and erythrocyte volume fraction (EVF) to differentiate between
      patients with acute mesenteric ischaemia (AMI), perforation of colon, perforation
      of peptic ulcer, and intestinal obstruction. The WBC in patients with AMI (18.95
      +/- 6.88 10(3) ml-1) was significantly above the normal range (upper cut-off 11.0
      10(3) ml-1; P < 0.0001). Other variables in the patient groups did not differ
      from those of healthy individuals. All variables were, however, different between
      patients with AMI and non-AMI (P < 0.001). Receiver operator characteristic (ROC)
      curves were constructed to define the optimal cut-off for each variable.
      Sensitivity and specificity of the variables were between 62% and 75%.
      Discriminant analysis of the variables classified 80% of the patients correctly
      into AMI and non-AMI groups.

PMID- 8292469
TI  - Venepuncture causes rapid rise in plasma ACTH.
AB  - Serum cortisol and adrenocorticotropin (ACTH) levels were measured on nine
      sleeping volunteers at midnight, before and after the stress of being woken and
      exposed to a single standard venepuncture. In six volunteers, plasma ACTH levels
      were raised within 90 seconds of venepuncture, while it remained undetectable in
      the other three. Cortisol levels began to rise within 4 minutes. ACTH and
      cortisol levels may be greatly altered by the stress of venesection. Plasma ACTH
      measured after a difficult venesection in a subject with poor venous access may
      be misleading.

PMID- 8292470
TI  - The surgical treatment of hyperparathyroidism: a regional hospital experience.
AB  - Parathyroidectomy is an established surgical treatment for symptomatic
      hyperparathyroidism. In this regional hospital experience, 50 patients who had
      undergone a parathyroidectomy were looked at. We examined clinical indications
      and noted trends for hypertension, neuromuscular symptomatology and psychiatric
      complaints to occur commonly as presenting symptoms. Operative results and
      histology results are examined and correlated. Particular note is made of any
      postoperative complications.

PMID- 8292471
TI  - Audit of patients' experiences after endoscopy of the upper alimentary tract.
AB  - This study comprises an audit of the experiences of upper alimentary endoscopy by
      400 patients examined in 15 hospitals. The patients were asked to complete a 19
      section questionnaire regarding their experience of the endoscopy before, during
      and after the procedure. The audit was carried out in order to evaluate the
      patients' understanding of the investigation and to determine the impact of the
      findings on the patients' level of anxiety. Of the 400 patients, 304 (76.0%)
      returned the questionnaire; overall satisfaction was revealed with the decision
      to proceed with endoscopy and with the procedure itself, as well as the
      reassurance provided by the investigation. The study thus supports the role of
      open-access endoscopy.

PMID- 8292472
TI  - Clinical audit: is day-case adenotonsillectomy safe?
AB  - The trend towards day-case procedures is growing, as a consequence not only of
      improved medical care but the increasing importance of economic considerations in
      today's healthcare environment. In the largest worldwide study to date to assess
      the safety of day-case adenotonsillectomy, we reviewed the records of 4386
      patients at the otolaryngology department of the Bradford Royal Infirmary. We
      found a reactionary haemorrhage rate of 0.57%. All patients who underwent surgery
      in the morning session had presented with haemorrhage and returned to the
      operating theatre before the end of the afternoon session. We discuss the
      implications of these findings, and consider that with careful monitoring day
      case tonsillectomy and/or adenoidectomy may safely be introduced.

PMID- 8292473
TI  - The investigation and management of gastro-oesophageal reflux disease.

PMID- 8292474
TI  - Recent advances in the understanding of the immunological basis of peripheral
      neuropathies.
AB  - This article briefly reviews some recent advances in the understanding of the
      immunological basis of peripheral neuropathies. Peripheral neuropathies
      associated with paraproteinaemia, though rare, have proven paradigmatic, some of
      the insights gained being applicable to the more common Guillain-Barre syndrome.

PMID- 8292475
TI  - Computed tomography in crepitant myonecrosis.
AB  - We report an unusual case of non-traumatic myonecrosis presenting as hip pain.
      Computed tomography helped to define the extent of the infection and its origin
      in the presacral space. The use of CT in diagnosis and management of gas-forming
      soft tissue infection is reviewed.

PMID- 8292476
TI  - Covert hypothyroidism with weight loss and atrial fibrillation.
AB  - Hypothyroidism may present with weight gain and/or cardiovascular manifestations
      such as bradycardia or cardiac failure, but has not previously been documented as
      presenting with atrial fibrillation and weight loss. Our case highlights the
      importance of thyroid function tests in heart failure and emphasises the
      importance of regular follow-up after irradiation to the thyroid.

PMID- 8292477
TI  - Hepatic artery aneurysm: an unusual presentation.
AB  - The natural history of visceral artery aneurysms, and in particular those of the
      hepatic artery, is unclear. The clinical presentation can include upper abdominal
      pain, bleeding into the gastrointestinal tract, and obstructive jaundice. We
      present the case of a middle-aged woman with right upper quadrant pain and a
      palpable mass, in whom a thrombosed hepatic artery aneurysm was found to be the
      cause.

PMID- 8292478
TI  - Common femoral artery fenestration in the treatment of thoracic aortic
      dissection.

PMID- 8292479
TI  - Pneumoperitoneum due to PCI in a patient with a strangulated femoral hernia.
AB  - Although pneumatosis cystoides intestinalis (PCI) is a well-recognised condition,
      an individual surgeon is unlikely to encounter it often. The collected experience
      of two surgical units in Glasgow teaching hospitals over a 15-year period
      consisted of five patients. Surgical and radiological trainees may therefore have
      little or no exposure to the diagnostic difficulties this condition can cause. We
      report an illustrative case.

PMID- 8292480
TI  - Congenital fistulation of a Meckel's diverticulum to the surface of an exomphalos
      sac.
AB  - Exomphalos and vitellointestinal duct remnants are well-known entities. This
      report details the presentation of congenital fistulation of a Meckel's
      diverticulum to the surface of an exomphalos minor.

PMID- 8292481
TI  - Partial malrotation associated with pseudo-obstruction of the small bowel.
AB  - Intestinal pseudo-obstruction is defined as a syndrome in which there are signs
      and symptoms of intestinal obstruction without an actual obstructing lesion. In
      many cases it is associated with other disease entities but may be idiopathic. We
      report a case associated with partial malrotation of the gut which has not been
      described in the literature before.

PMID- 8292482
TI  - Intestinal malabsorption presenting with night blindness.
AB  - Night blindness from vitamin A deficiency was observed in a patient with
      intestinal malabsorption, which in turn was attributable to duodenal
      diverticulosis and bacterial growth. Monthly supplementation with vitamin A and
      correction of bacterial overgrowth with tetracycline resulted in a normalisation
      of plasma retinol levels and resolution of the night blindness.

PMID- 8292483
TI  - Massive lower gastrointestinal haemorrhage secondary to metastatic squamous cell
      carcinoma of the lung.
AB  - Clinically significant symptoms due to gastrointestinal metastases from primary
      lung cancers is rare. A case of life-threatening lower gastrointestinal
      haemorrhage secondary to metastatic squamous cell carcinoma of the lung is
      reported. Previous reports of such metastases are reviewed, with reference to
      management and prognosis. After resection of colonic metastases from squamous
      cell lung cancer, survival is similar to that for primary disease. It is
      suggested that patients with known or suspected squamous cell lung cancer
      presenting with lower gastrointestinal symptoms be managed as aggressively as
      those with no previous history of disease.

PMID- 8292484
TI  - Fournier's gangrene.
AB  - Fournier's gangrene was traditionally thought to arise spontaneously. More
      recently, cases with urological, perianal or systemic predisposing causes have
      been reported. This report describes four cases of Fournier's gangrene, all
      associated with a predisposing cause: two with diabetes mellitus, two secondary
      to urinary tract pathologies, and one secondary to an infected wound after an
      inguinal herniorrhaphy.

PMID- 8292485
TI  - Bleeding duodenal varices.

PMID- 8292486
TI  - Mechanisms of humoral fractures in arm wrestlers.

PMID- 8292487
TI  - Identification of novel catecholamine absorbing proteins in the central nervous
      system.
AB  - Several pharmacologically active catecholamines have been shown to react
      covalently with CNS proteins, namely species of 47, 40, 22, and 20 kDa. Of these,
      the 47-kDa protein showed the greatest incorporation of tritium following
      treatment with [3H]dopamine, [3H]ADTN, or [3H]N-propyl-norapomorphine. Labeling
      was accomplished by incubating the tritiated ligands with crude membrane
      preparations in the absence of reducing agents. These proteins displayed several
      unique characteristics: 1. The proteins are distributed throughout the CNS, but
      no evidence was found for their presence in other tissues; 2. The proteins have a
      unique pharmacological profile, interacting with dopamine, ADTN, N-propyl
      norapomorphine, and apomorphine, but not with ligands specific for other proteins
      known to interact with these compounds; 3. The labeling of these proteins is not
      inhibited by several similar catecholamines and other catechols, suggesting
      specific structural requirements; and 4. These proteins exhibited
      stereoselectivity with respect to this labeling. These results demonstrate the
      existence of novel CNS proteins capable of covalently absorbing several
      physiologically important catecholamines in vitro.

PMID- 8292488
TI  - Cycloheximide prevents kainate-induced neuronal death and c-fos expression in
      adult rat brain.
AB  - The present study was directed at evaluating the possible involvement of protein
      synthesis in excitotoxin-induced neuronal damage and prolonged expression of the
      proto-oncogene, c-fos. Kainic acid-induced seizure activity elicited varying
      degrees of neuronal damage and cell loss in selectively vulnerable regions of the
      adult rat limbic system. Pretreatment with cycloheximide, a protein synthesis
      inhibitor, did not alter behavioral seizure characteristics, but markedly
      attenuated damage to susceptible neuronal populations. A prolonged increase in c
      fos mRNA was observed by in situ hybridization up to 16 h after the onset of
      seizures in regions exhibiting neuronal death. Pretreatment with cycloheximide
      did not affect the transient induction of c-fos observed in numerous structures,
      but significantly reduced the prolonged expression of c-fos mRNA in kainate
      vulnerable regions. Despite producing massive seizure activity, systemic kainic
      acid administration during the early postnatal period did not induce any neuronal
      death, and did not result in prolonged c-fos expression in any brain structures.
      The developmental onset of selective neuronal vulnerability coincided with that
      of prolonged c-fos expression in susceptible neuronal populations. In adult rats,
      seizure activity induced by pentylenetetrazole did not produce neuronal damage
      nor did it produce prolonged c-fos expression. These results not only demonstrate
      that kainate-induced neurotoxicity and the prolonged expression of c-fos are both
      prevented by cycloheximide, but also strengthen idea that prolonged c-fos
      expression is a marker of neuronal death.

PMID- 8292489
TI  - Synthesis and characterization of a bioactive 82-residue sphingolipid activator
      protein, saposin C.
AB  - The sphingolipid activator protein, saposin C (also termed SAP 2), was chemically
      synthesized, purified, and characterized. The fully protected 82-residue protein
      was synthesized by automated solid-phase methods, with multiple recoupling steps
      resulting in a high average coupling efficiency of 98.8%. The overall yield was
      estimated to be approx 40%. Deprotection and cleavage of the peptide from the
      resin was followed by folding in the absence of chaotropic agents at pH 8.5. The
      protein was purified by reversed-phase high pressure liquid chromatography (HPLC)
      and its purity determined by capillary electrophoresis and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). The composition of the synthetic
      saposin C was determined by amino acid analysis. Its sequence was verified by
      Edman sequence analysis of overlapping peptide fragments generated by
      chymotryptic and Staphylococcus aureus V8 digestions. The sequence at the C
      terminus was determined by digestion with carboxypeptidase P, followed by
      phenylthiohydantoin (PTH) derivitization and HPLC analysis of the released amino
      acid residues. Deglycosylated native saposin C appeared as a lower molecular
      weight species than synthetic saposin C on SDS-PAGE. This has been explained by
      amino acid and C-terminal analysis showing native saposin C to be two amino acids
      shorter at the C terminus than a deduced sequence (from cDNA) previously
      published. Synthetic saposin C displayed 85% of full biological activity as
      determined by its ability to stimulate glucocerebrosidase activity in vitro:
      Synthetic and native saposin C increased glucocerebrosidase catalyzed hydrolysis
      of 4-methylumbelliferyl beta-D-glucoside by factors of 6.0 and 7.1, respectively.
      Furthermore, synthetic and native saposin C share similar K(act) values (0.5 and
      1.5 microM respectively) indicating that they bind to glucocerebrosidase with
      similar affinities.

PMID- 8292490
TI  - Effects of cAMP, glucocorticoids, and calcium on dopamine beta-hydroxylase gene
      expression in bovine chromaffin cells.
AB  - To better understand the molecular mechanism underlying regulation of bovine
      dopamine beta-hydroxylase (DBH), the effects of elevated intracellular cAMP,
      glucocorticoids, and calcium were studied in primary cultured chromaffin cells.
      Elevation of intracellular cAMP by forskolin and treatment with its analog 8
      bromo-cAMP caused an increase in the bovine DBH mRNA level by 3.5 +/- 0.5- and
      7.8 +/- 0.9-fold, respectively, which was maximal at 6 h after the treatments. On
      the other hand, dexamethasone elicited no apparent change in DBH gene expression
      at various concentrations and time. The combined treatment with forskolin and
      dexamethasone resulted in the same degree of increase as that with forskolin
      alone. Increased intracellular calcium by the ionophore A23187 ranging from 50 to
      500 nM caused DBH mRNA to decrease, which began to be observed after 6 h and was
      undetectable by 48 h. The results demonstrate the existence of coordinate and
      differential regulations among the enzymes involved in catecholamine biosynthesis
      in bovine adrenomedullary cells.

PMID- 8292491
TI  - Learning and sexual deficiencies in transgenic mice carrying a chimeric
      vasoactive intestinal peptide gene.
AB  - The molecular mechanisms responsible for behavior are largely unknown. A state of
      the art model, paving the path from genes to behavior, is offered by transgenic
      animals. Candidate molecules are classic neuropeptides, such as vasoactive
      intestinal peptide (VIP). Transgenic mice harboring a chimeric VIP gene driven by
      the polyoma promoter were produced. Behavioral studies revealed learning
      impairment and prolonged retardation in memory acquisition in the genetically
      altered animals. Furthermore, reduced performance was observed when the male
      transgenic mice were tested for sexual activity in the presence of receptive
      females. Surprisingly, radioimmunoassays showed an approx 20% decrease in the VIP
      content of the transgenic mice brains. To directly assess genetically reduced VIP
      content as a cause for learning impairment, transgenic mice carrying diphtheria
      toxin-encoding sequences driven by the rat VIP promoter were created. These
      animals had reduced brain VIP and exhibited deficiencies in learning abilities,
      strongly supporting an important neurobiological function for VIP in vivo.

PMID- 8292492
TI  - Isolation of a peptide that inhibits the posttranslational arginylation of
      proteins in rat brain.
AB  - All eukaryotic cells contain enzymes that are able to catalyze the transfer of
      Arg from tRNA to the N-terminus of naturally short lived or damaged cytosolic
      proteins. For certain test proteins, it has been shown that the addition of Arg
      to the N-terminus leads to their degradation via the ubiquitin proteolytic
      pathway. The mechanisms used by cells for identifying proteins for arginylation
      and regulating arginylation are not known. The present study reports the
      isolation of a peptide from rat brain that is able to inhibit the arginylation of
      proteins in brain extracts. We suggest that this peptide is the physiological
      regulator of arginylation in rat brain.

PMID- 8292493
TI  - Intracellular magnesium movements and lymphocyte activation.
AB  - Activation of lymphocytes through ligation of the antigen receptor complex
      initiates activation of phospholipase C-gamma (PLC). Activated PLC hydrolyses
      phosphatidylinositol-4,5-bisphosphate into diacylglycerol (DAG) and inositol
      1,4,5-trisphosphate (InsP3). InsP3 mediates the release of Ca2+ from
      intracellular stores into the cytoplasm, while InsP4 and InsP3 mobilize
      extracellular Ca2+. Both processes contribute to the temporary increase in
      [Ca2+]i that is observed after lymphocyte activation. Because of the availability
      of Mg(2+)-sensitive and specific fluorochromes like Mag-indo-1 it is now possible
      to monitor potential changes in [Mg2+]i. In lymphocytes that have responded to
      receptor activation with high [Ca2+]i, an increase in [Mg2+]i can be found. The
      [Mg2+]i is in the range that enables it to modulate the activity of a number of
      cellular enzymes, including key enzymes in the PLC transmembrane signalling
      pathway. It can be speculated that a differential Mg2+ mobilization response will
      have consequences for the ultimate cellular response to receptor activation.

PMID- 8292494
TI  - Relationship between magnesium and elastic fibres.
AB  - The presence of magnesium was demonstrated by histochemical methods in elastic
      fibres from different locations. After pretreatment with elastase a positive
      reaction could no longer be detected. Microfibrils which enclose the elastin core
      of the elastic fibres gave no positive reaction. These results support the
      supposition of a close relationship between Mg and elastin. Determination of the
      Ca/Mg ratio by atomic absorption spectrometry in variants of fibrous connective
      tissue showed a decreasing Ca level with increasing elasticity. The Ca/Mg ratio
      in lattices containing rubber-like particles disclosed striking diminution of Ca.
      These data support the speculation that the antagonism of Mg to Ca plays a
      fundamental role in the maintenance of elasticity. The special interaction of the
      Mg2+ ion with water molecules is very probably a further prerequisite for
      elasticity in natural elastic materials.

PMID- 8292495
TI  - Body composition, health status and urinary magnesium excretion among elderly
      people (Dutch Nutrition Surveillance System).
AB  - Magnesium (Mg) requirements depend on body weight. Recommended dietary allowances
      (RDA) are mostly given in absolute amounts and are mostly similar for adults,
      despite differences in body composition in the adult age range. We therefore
      studied the interrelations of 24 h urinary Mg excretion with body build and body
      composition indicators, as well as with factors potentially affecting the
      metabolism of Mg, among 520 elderly men and women seen in a nationwide survey. Mg
      intake data were also obtained in the Dutch Food Composition Survey amount 5898
      subjects. The results showed lower mean Mg intake among elderly people
      (especially men) and positive associations of body weight and body height with
      urinary Mg excretion, but not when expressed per mmol of creatinine excreted. Mg
      excretion per mmol of creatinine was not associated with body weight, body
      height, body mass index or body fatness (women), suggesting that the amount of
      fat mass did not affect Mg excretion. Mg excretion was positively correlated with
      Mg intake, creatinine clearance, excretion of sodium, potassium and calcium, and
      coffee consumption, indicating interactions at the kidney level that may increase
      Mg losses. Elderly people using diuretics and/or anticholinergics and male
      diabetics had a higher mean Mg excretion per mmol of creatinine. The results show
      that, besides the Mg intake, several factors affect the urinary Mg excretion
      among elderly people. These factors were body build and body composition, dietary
      intake, drug use, kidney function, and diabetes. A quantification of the effects
      cannot be made yet, and controlled studies on those factors potentially affecting
      the requirement of Mg are needed.

PMID- 8292496
TI  - Preliminary study of the relationship between plasma and erythrocyte magnesium
      variations and some circulating pro-oxidant and antioxidant indices in a
      standardized physical effort.
AB  - The aim of this preliminary study was to determine the relationship between
      exercise, magnesium (Mg) status, oxidative stress, and antioxidant defence
      systems. Some corresponding indices have been evaluated: plasma Mg, ascorbate,
      uric acid, adrenaline, creatine kinase (CK), thiobarbiturate reactive substances,
      adrenochrome; and in erythrocytes (RBC): reduced and oxidized glutathione (GSH
      and GSSG) and Mg. Venous blood samples were withdrawn before and 3 min after
      completion of a 40 min run. Only two significant changes were observed after
      effort: plasma Mg decreased (P < 0.009) and plasma adrenaline increased (P <
      0.005). There was a non-significant tendency for indices of oxidative stress and
      antioxidant capacity to increase. The significant correlations between plasma Mg
      and CK (r = -0.88) and between RBC Mg and plasma ascorbate (r = -0.76)
      disappeared after the effort. Further research is necessary, with a larger number
      of subjects and variables, to obtain a better understanding of these
      interactions.

PMID- 8292497
TI  - Doppler assessment of retinal blood flow velocity during parenteral magnesium
      treatment in patients with preeclampsia.
AB  - Preeclampsia is frequently treated with the intravenous infusion of magnesium
      sulphate, which is well known to control seizures in the eclamptic patient. The
      effects of this drug on the cerebral vasculature, however, are not well defined.
      Doppler ultrasound allows the evaluation of changes in blood flow velocity in
      vessels previously inaccessible to researchers. This technology has recently been
      applied to the study of the retinal effects of parenteral magnesium sulphate. The
      efficacy of this agent as a small vessel cerebral vasodilator has been
      demonstrated, both in the middle cerebral artery and in the orbital vessels. This
      new technique may shed light on the pathophysiology of preeclampsia and on the
      mechanism of action of magnesium sulphate in this disease.

PMID- 8292498
TI  - Effects of silicon, fluoride, etidronate and magnesium on bone mineral density: a
      retrospective study.
AB  - A retrospective study of bone mineral density (BMD) changes was performed in 53
      osteoporotic women prior to carrying out a prospective study. Comparisons between
      BMD of controls (n = 16) and treated groups over a 14-22 month period showed that
      fluoride (n = 10) induced a significant (P < 0.05) increase in vertebral and a
      slight decrease in femoral BMD, whereas silicon (n = 8) induced a significant (P
      < 0.05) increase in femoral BMD. Etidronate (n = 13) and, to a lesser extent,
      magnesium (n = 6), induced a slight although statistically non-significant
      increase in vertebral BMD.

PMID- 8292499
TI  - A physiological oral magnesium supplement does not influence total serum
      magnesium, left ventricular ejection fraction and prognosis in patients with
      dilated cardiomyopathy.
AB  - It has been postulated that patients with congestive heart failure (CHF) benefit
      from physiological oral magnesium supplements. In order to study the effect of
      such supplements upon patients with idiopathic dilated cardiomyopathy (IDC) we
      studied a group of 23 patients with the salient characteristics of IDC (18 male,
      5 female; mean age 51 +/- 13 years [range: 23-72]; Mg group), who received oral
      magnesium supplements (15 mmol/day). All patients received oral ACE inhibitors
      and 22 were receiving digitalis and diuretics. A control group of 27 patients,
      matched for age, sex, symptoms, and additional treatment (22 male, 5 female; mean
      age 52 +/- 13 years [range 22-71]) were not given oral magnesium supplements. All
      these patients also received oral ACE inhibitors, 25 were receiving digitalis,
      and 23 were receiving diuretics. Mean serum magnesium concentration (total serum
      Mg) in the Mg group was 0.83 +/- 0.06 mmol/litre [mean +/- SD, range 0.69-0.99],
      while in the control group it was 0.83 +/- 0.07 mmol/litre [range 0.70-0.96], P =
      NS. Left ventricular ejection fraction (LV-EF) improved from 32 +/- 11 per cent
      [range 13-51] to 42 +/- 14 per cent [range 15-66] in the Mg group and from 30 +/-
      13 per cent [range 10-52] to 42 +/- 11 per cent [range: 25-64] in the control
      group. We found that physiological oral Mg supplements did not influence serum
      magnesium, LV-EF, or prognosis. Furthermore, we found that 56 per cent of all
      patients improved when subjected to strict guidance and therapy with ACE
      inhibitors, digitalis, and diuretics.

PMID- 8292500
TI  - Magnesium, potassium flux and photosynthesis.
AB  - Photosynthetic capacity of chloroplasts is regulated by stromal pH. The pH of the
      stroma must be maintained higher than external pH during illumination in order to
      optimize photosynthetic carbon reduction cycle activity. Stromal pH is affected
      by K+/H+ counterexchange across the chloroplast envelope. Magnesium ion external
      to the chloroplast affects K+/H+ counterfluxes and hence stromal pH and
      photosynthesis. K+/H+ counterfluxes across the envelope are facilitated by K+ and
      H+ conducting ion channels, and an H+ pumping envelope ATPase. External magnesium
      affects K+/H+ exchange by binding to negative surface charges on the envelope
      membrane. Magnesium binding restricts currents through K+ channels. Magnesium
      block of K+ uptake through this channel impairs H+ efflux, inhibiting
      photosynthesis. Under conditions which lead to net K+ efflux through the channel,
      envelope-bound magnesium restricts K+ efflux, reducing the driving force for
      electroneutral H+ uptake. External magnesium has a profound effect on chloroplast
      photosynthetic capacity by an indirect control of H+ movement across the envelope
      and hence of stromal pH.

PMID- 8292501
TI  - Intracellular magnesium and inositol 1,4,5-trisphosphate receptor: molecular
      mechanisms of interaction, physiology and pharmacology.
AB  - This review focuses on the action of intracellular magnesium ion on the inositol
      1,4,5-trisphosphate (IP3) receptor, the almost ubiquitous membrane-bound Ca2+
      channel gated by the intracellular second messenger IP3. Experimental data have
      shown that Mg2+ is a non-competitive inhibitor of the IP3-gated Ca2+ channel and
      of [3H]-IP3 binding. The relevance of the Mg2+ effect is discussed in relation
      to: (a) the physiological role of the IP3-induced release of Ca2+ from
      intracellular Ca2+ stores, i.e., Ca2+ homeostasis of activated cells, in
      particular cardiac myocytes; (b) the modulation exerted by changes of [Mg2+]o and
      [Mg2+]i on basic cardiac functions, e.g., inotropism, chronotropism and
      automaticity; and (c) the pathogenesis of automatic arrhythmias, caused by either
      early or delayed afterdepolarizations, in which IP3-induced release of Ca2+ may
      be involved.

PMID- 8292502
TI  - On the use of parenteral magnesium salts in the treatment of acute ischaemic
      heart disease: a brief review.
AB  - With the advent of pharmacological, mechanical and surgical revascularization as
      firstline therapies in acute coronary artery disease syndromes, the search for
      adjunctive pharmacotherapy against reocclusion and reperfusion injury has
      intensified. In addition, safe pharmacotherapeutic intervention conferring
      survival advantage is required for those at high risk ineligible for
      recanalization or beta blockade. Of major importance, in this vein, is the
      intriguing association between parenteral magnesium and the amelioration of
      myocardial ischaemia and the eradication of lethal ischaemic ventricular
      arrhythmias reasserted in both animal and human studies. In addition, in more
      recent years, parenteral magnesium has been linked to the amelioration of
      reperfusion injury in animal experiments. In this paper we shall review the
      literature with respect to myocardial ischaemia, its pathophysiology and
      treatments. In doing so, we shall present data that strongly supports the
      logistic use of parenteral magnesium compounds as essential therapy in the
      treatment of acute ischaemic heart disease associated with necrosis, and a
      potential role in ablating reperfusion injury.

PMID- 8292503
TI  - The relationship between boron and magnesium status and bone mineral density in
      the human: a review.
AB  - Osteoporosis is a disease that characteristically afflicts postmenopausal women.
      It is estimated that millions of people are plagued yearly with this debilitating
      disease. Associated health care costs are in the billions of dollars, annually.
      Much research has been conducted in the area of osteoporosis and mineral
      supplementation, mainly focusing on calcium and vitamin D. Nonetheless, more
      recent studies have reported possible improvements in bone mineral density in
      women who were supplemented with the ultratrace mineral, boron. Boron may play a
      role in bone metabolism, but its role is most likely to be associated with its
      interactions with other minerals and vitamins such as calcium, magnesium and
      vitamin D. Although the focus of this review will be to discuss the interactive
      role of boron with magnesium and bone metabolism, some discussion of its
      interactive role with vitamin D is also necessary.

PMID- 8292504
TI  - Commentary on recent clinical advances: death from infancy to older age and
      marginal maternal magnesium deficiency. How long should the follow-up of the
      consequences of undernutrition in pregnancy be continued?

PMID- 8292505
TI  - Noncytotoxic approaches to the treatment of HIV-associated Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) is an otherwise unusual disease that frequently complicates
      the course of HIV infection. While there is some evidence to suggest that the
      pathogenesis of KS is driven by a variety of cytokines and cellular factors, the
      exact pathogenesis of the disease is unknown at present. Current therapy for HIV
      associated KS has been developed empirically and involves, for the most part,
      classic cytotoxic chemotherapy. However, as more is learned about the
      pathogenesis of KS lesions, new and novel therapeutic modalities may emerge aimed
      at interrupting or blocking the activity of the pathogenetic factors involved.

PMID- 8292506
TI  - Clinical trials referral resource. Metastatic breast cancer.

PMID- 8292507
TI  - Mammography and breast examination for older women--results from Behavioral Risk
      Factor Surveillance System, 1992.

PMID- 8292508
TI  - Nutrition and breast cancer.
AB  - A range of current information links nutrition and dietary factors to the risk of
      developing breast cancer, as well as to survival and outcomes after a diagnosis
      of breast cancer. Epidemiologic and other data suggest that high-fat and low
      fiber diets are associated with an increased risk of breast cancer. Several pilot
      intervention studies have been performed to decrease dietary fat intake in women
      with breast cancer. Other studies suggest that weight gain after breast cancer is
      common and may be detrimental to survival. Taken together, all of these data
      suggest that further studies should be undertaken to better understand the
      relationship between nutritional factors and the development of breast cancer.

PMID- 8292509
TI  - Behavioral treatment of chemotherapy-induced nausea and vomiting.
AB  - Nausea and vomiting associated with chemotherapy most commonly occur after
      administration of the drug regimen, but a substantial proportion of patients also
      develop these symptoms in anticipation of treatment, after one or more courses of
      chemotherapy have been given. Currently available pharmacologic agents are unable
      to provide complete protection from either anticipatory or post-treatment nausea
      and emesis associated with cancer chemotherapy. Since anticipatory nausea and
      vomiting are believed to become conditioned responses through the learning
      process of classical conditioning, behavioral treatments may be particularly
      appropriate. Progressive muscle relaxation training is effective in preventing as
      well as decreasing the frequency of postchemotherapy nausea and vomiting, whereas
      systematic desensitization has been found to be more effective against
      anticipatory nausea and emesis. Hypnosis and cognitive distraction have been used
      mainly in children and adolescents.

PMID- 8292510
TI  - Pediatric hematology and oncology in the United Kingdom.

PMID- 8292511
TI  - Definitions and dogma in childhood idiopathic thrombocytopenic purpura.

PMID- 8292512
TI  - Pediatric hematology and oncology in Iran: past and present state.

PMID- 8292513
TI  - Cerebrovascular complications of L-asparaginase therapy in children with
      leukemia: aphasia and other neuropsychological deficits.
AB  - Children with acute lymphoblastic leukemia (ALL), treated with L-asparaginase are
      at risk for cerebral thrombosis or hemorrhage because of coagulation protein
      deficiencies. The results and the importance of serial neuropsychological
      examinations after such complications in three children with ALL are presented.
      All patients showed marked aphasia and other cognitive deficits. Recovery was
      complete in two of three children.

PMID- 8292514
TI  - Spectrum of clinical manifestations of antiphospholipid antibodies in childhood
      and adolescence.
AB  - Nineteen children with circulating anticoagulants or anticardiolipin antibodies
      and negative or only weakly positive antinuclear factors were reviewed for their
      clinical manifestations. The relationship between these antibodies and the
      morbidity in the pediatric age group will be discussed.

PMID- 8292515
TI  - Oral megadose methylprednisolone versus intravenous immunoglobulin for acute
      childhood idiopathic thrombocytopenic purpura.
AB  - Twenty children with acute idiopathic thrombocytopenic purpura (ITP) were
      randomized to receive either oral megadose methylprednisolone (MDMP) or
      intravenous immunoglobulin G (IV IgG). Normal platelet counts (> or = 150 x
      10(9)/l) were obtained in 6 patients of each group in 3 days and in 8 and 9
      patients treated with oral MDMP and with IV IgG within 1 week, respectively. It
      is concluded that oral MDMP could easily be used for the early elevation of
      platelet counts, which is important for ITP treatment.

PMID- 8292516
TI  - Intravenous corticosteroids versus intravenous gammaglobulin in the treatment of
      acute immune thrombocytopenic purpura.
AB  - Debate continues over the most appropriate treatment for children with acute
      immune thrombocytopenic purpura (ITP). An institutional review of all admissions
      for acute ITP between 1986 and 1991 found 61 children treated with intravenous
      (i.v.) IgG or i.v. steroids with a bone marrow aspirate consistent with ITP, an
      age of 21 years or younger, and an admission platelet count of < or = 20,000/mm3.
      The efficacy of these two agents was compared in the described population. A
      response was defined as achieving a platelet count of > or = 50,000/mm3. A
      significantly greater percentage of patients responded to i.v. IgG compared to
      i.v. steroids during the first 36 hr of therapy; however, by 72 hr of treatment
      there was no significant difference. The cost of hospitalization was 3 1/2 times
      greater for the patients responding to i.v. IgG vs. i.v. steroids.

PMID- 8292517
TI  - Renal autotransplantation--a kidney saving procedure before spinal radiotherapy.
AB  - Renal damage is a well-known consequence of radiation therapy to adjacent tumors.
      We describe a child requiring spinal irradiation in whom autotransplantation of a
      kidney to a site outside the radiation field was performed and the renal function
      preserved.

PMID- 8292518
TI  - Squamous cell carcinoma in the sacrococcygeal area: a case report and review of
      the literature.
AB  - Squamous cell carcinoma is a rare malignancy in the pediatric age group. We
      describe a 12-year-old boy with squamous cell carcinoma of the sacrococcygeal
      region. This is the first reported case of that pathology in this region. The
      patient was treated with surgery, chemotherapy and radiation therapy and is now
      free of disease 3 years later. The etiology of sacrococcygeal squamous cell
      carcinoma is unclear, and its possible pathophysiology in relation to its
      location is discussed.

PMID- 8292519
TI  - Acute febrile neutrophilic dermatosis (Sweet's syndrome) in myelodysplastic
      syndrome.
AB  - This is the first report of the rare association of acute febrile neutrophilic
      dermatosis (Sweet's syndrome) and myelodysplastic syndrome (MDS) in a child. The
      skin lesions showed a dramatic response to colchicine.

PMID- 8292520
TI  - Case of a child with paroxysmal nocturnal hemoglobinuria diagnosed by flow
      cytometry.
AB  - A case of a child with paroxysmal nocturnal hemoglobinuria (PNH) is characterized
      by an increased sensitivity of the erythrocyte to hemolytic action of complement.
      The widely used Ham test may not always be reliable. Recently, a panel of
      monoclonal antibodies has become available to detect various
      glycosylphosphatidylinositol (GPI)-linked proteins by flow cytometry (FCM) and
      the deficiency of GPI-anchored proteins on the various kinds of cell membranes is
      implicated as the pathogenesis of PNH. We diagnosed a case of a child with PNH by
      FCM and complement lysis sensitivity (CLS) test, which showed the increased
      sensitivity of PNH erythrocytes to complement. His diagnosis was delayed because
      of Ham test negativity and rarity of PNH cases in children.

PMID- 8292521
TI  - Cytomegalovirus infection in two infants with congenital or neonatal solid
      tumors.
AB  - Two infants with fibrosarcoma and rhabdomyosarcoma diagnosed prenatally and at 2
      months of age, respectively, and cytomegalovirus (CMV) infection are reported.
      Concomitant CMV infection was revealed by positive urine culture and/or CMV DNA,
      and CMV-specific IgM, IgA, and complement-fixing antibodies. The patients,
      showing very low levels of immune T cells, died at 3 and 8 months of age,
      respectively. A pathogenic role for CMV in the progression of the tumors is
      suggested.

PMID- 8292522
TI  - Limb congenital fibrosarcoma: report of two cases and review of the literature.
AB  - Two cases of limb congenital fibrosarcoma are reported. The use of postsurgery
      chemotherapy allowed conservative surgery in one of them. Wide local excision
      appears to be the treatment of choice unless the size of the tumor and its
      anatomic location requires amputation. Additional chemotherapy could shift the
      surgical approach to one of less radical surgery.

PMID- 8292523
TI  - All-trans retinoic acid as an alternative to chemotherapy in the treatment of
      acute promyelocytic leukemia.
AB  - A 12-year-old girl with acute promyelocytic leukemia has been treated with
      conventional chemotherapy. The patient remained in complete remission for a year
      when the first bone marrow relapse occurred. Since reinduction chemotherapy was
      rejected by the parents, an alternative treatment with oral all-trans retinoic
      acid was administered. A second complete remission was achieved within 100 days.
      After 14 months a second bone marrow relapse occurred. All-trans retinoic acid
      and the combination with interferon-alpha failed.

PMID- 8292524
TI  - Autoimmune neutropenia of infancy and early childhood.
AB  - Forty-one children were identified with autoimmune neutropenia of infancy and
      early childhood (absolute neutrophil count [ANC] less than 500/microliters and
      demonstrable serum antineutrophil antibodies). There were 21 boys and 20 girls;
      the median age at diagnosis was 11 months (range 5-38 months). No life
      threatening infections occurred. There was a gradual upward trend in ANC in all
      patients over many months, with 87% having an ANC > 1000/microliters by 24 months
      from diagnosis. Among various clinical and laboratory parameters analyzed
      statistically, only younger age at diagnosis was associated with earlier
      neutrophil recovery. There was no association between degree or duration of
      neutropenia and sex, race, antibody reactivity, or presence of serious illness at
      diagnosis.

PMID- 8292525
TI  - High-dose intravenous immunoglobulin therapy, blood rheology, and sickle cell
      anemia.

PMID- 8292526
TI  - T cell leukemia with pericardial effusion at diagnosis.

PMID- 8292527
TI  - Thrombocytopenic purpura following DPT vaccination.

PMID- 8292528
TI  - Avascular necrosis of bones in children with sickle cell anemia.

PMID- 8292529
TI  - Tuberculosis preventive therapy in HIV-infected individuals. A Joint Statement of
      the WHO Tuberculosis Programme and the Global Programme on AIDS, and the
      International Union Against Tuberculosis and Lung Disease (IUATLD).

PMID- 8292530
TI  - Emerging infectious diseases.

PMID- 8292531
TI  - Localization of RIHB (retinoic acid-induced heparin-binding factor) transcript
      and protein during early chicken embryogenesis and in the developing wing.
AB  - Previously, we isolated an avian protein which we named retinoic acid induced
      heparin binding factor (RIHB). RIHB is a 121 amino acid secreted polypeptide,
      rich in basic and cysteine residues (Vigny et al., Eur. J. Biochem. 186: 733-740,
      1989). Northern blot analysis indicates that the RIHB gene is transiently
      expressed during embryogenesis (Urios et al., Biochem. Biophys. Res. Com. 175:617
      624, 1991). Here we present an investigation of RIHB expression during early
      chicken embryogenesis by in situ hybridization and immunofluorescence studies. In
      the 3-day embryo (stage 20-21), the RIHB transcript is observed throughout the
      embryo, with the notable exception of the neural tube. At this stage the protein
      can be visualized in almost all of the basement membranes and around many types
      of cells. The localization of the RIHB protein does not strictly parallel that of
      its messenger. Between days 3 and 11 we focused our attention on wing
      development. The level of both the mRNA and protein decreases during this period
      but the disappearance is not uniform. The level of both the mRNA and protein
      decreases during this period but the disappearance is not uniform. The transcript
      becomes progressively restricted to epithelia and regions surrounding the forming
      cartilage. In contrast to the transcript, the protein accumulates in the
      epithelial basement membrane and, interestingly, in the central part of the
      embryonic cartilage (diaphysis) but not in the distal parts (epiphysis). These
      data are discussed in relation to the putative role(s) of RIHB in development.

PMID- 8292532
TI  - Efficient incorporation of transfected blastodermal cells into chimeric chicken
      embryos.
AB  - The formation of transgenic chimeric chickens for use in developmental studies
      and as intermediates in the production of transgenic chickens requires the
      incorporation of stably transfected blastodermal cells into a chimera. To obtain
      blastodermal cells, area pellucidae of stage X (Eyal-Giladi and Kochav, Dev.
      Biol. 49:321-337, 1976:E.-G.&K.) embryos were collected from unincubated, freshly
      oviposited Barred Plymouth Rock eggs and dissociated in 0.25% trypsin/0.04% EDTA
      (w/v) and 2% (v/v) chicken serum in phosphate-buffered saline (Ca2+ and Mg2+
      free) at 4 degrees C for 10 min. The blastodermal cells were suspended in
      Dulbecco's Modified Eagle's Medium (DMEM) and transfected by lipofection with
      superhelical pmiwZ, a plasmid containing a hybrid lacZ gene encoding bacterial
      beta-galactosidase (beta-gal) under the control of a chicken beta-actin/Rous
      sarcoma virus promoter. A mixture of 2.5 micrograms Lipofectin and 1.56
      micrograms pmiwZ in 250 microliters DMEM was incubated for 30 min at 37 degrees C
      and added to 500 microliters of 20-40,000 cells in suspension. Cells incubated
      with the transfection reagents in the presence or absence of pmiwZ were either
      plated and cultured for 48 h at 37 degrees C in 5% CO2/95% air, or injected
      through a shell window into the subgerminal cavity of White Leghorn stage X (E.
      G.&K.) embryos previously exposed to 500-600 rads from a 60Co source, after which
      the window was sealed and the egg incubated at 38 +/- 1 degrees C for 72
      h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292533
TI  - EGF receptor and its ligands, EGF and TGF-alpha, in developing and neoplastic
      human odontogenic tissues.
AB  - Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha)
      regulate cell proliferation and functional maturation through the EGF receptor
      (EGF-R). Their roles in human tooth development and odontogenic tumorigenesis
      have not been explored. We studied the expression of EGF, TGF-alpha and EGF-R in
      human fetal teeth (cap stage to early hard tissue formation) and various
      odontogenic tumors. EGF-R mRNA and immunoreactive cells were mostly located in
      odontogenic epithelium. EGF-R expression was subject to temporospatial variation
      at different stages of tooth development. EGF and TGF-alpha mRNAs were detected
      in fetal teeth only by the reverse transcription polymerase chain reaction (RT
      PCR). However, EGF and TGF-alpha immunoreactive cells were demonstrated in
      epithelial elements of tooth germ, suggesting that the peptides partially
      originate from non-odontogenic sources. In odontogenic tumors, EGF-R mRNA and
      immunoreactivity were confined to neoplastic epithelium. Transcripts for TGF
      alpha but not for EGF were detected in tumors of odontogenic epithelial,
      epithelial-ectomesenchymal and ectomesenchymal origins. It is concluded that
      regulation of EGF-R expression is developmentally regulated in human
      odontogenesis. Furthermore, the odontogenic epithelium is the main target tissue
      for both EGF and TGF-alpha during tooth development. TGF-alpha and its receptor
      may also be involved in odontogenic tumorigenesis.

PMID- 8292534
TI  - Immunolocalization of HSP 70-related proteins constitutively expressed during
      Xenopus laevis oogenesis and development.
AB  - Using immunocytochemical and biochemical methods, we analyzed the localization of
      HSP 70-related proteins constitutively expressed during oogenesis and
      embryogenesis in the amphibian Xenopus laevis. Our results provided evidence for
      a regional localization in oocytes. In embryos, the regional distribution
      observed in oocytes was found to be maintained from fertilization up to late
      blastula. It is noteworthy that, at the beginning of gastrulation, nuclear
      transfer of such proteins had already occurred by the time of internalization in
      the involuting marginal zone (IMZ), whereas cells of the vegetal area exhibited
      only a perinuclear localization of these proteins. These results suggest that HSP
      70-related proteins might be involved in the control of the process of cellular
      internalization.

PMID- 8292535
TI  - The role of the mesonephros in cell differentiation and morphogenesis of the
      mouse fetal testis.
AB  - In mouse fetal gonads, the adjacent mesonephros is required for seminiferous cord
      formation in vitro (Buehr et al., Development 117: 273-281, 1993). Here, we have
      investigated the role of mesonephric cells in seminiferous cord formation and in
      differentiation of Sertoli and Leydig cells. Undifferentiated male gonads with
      and without mesonephros at 11.5 dpc were cultured and immunocytochemical staining
      of Mullerian-inhibiting substance (MIS) was used as the criterion for Sertoli
      cell differentiation. For Leydig cells, testosterone (T) radioimmunoassay and
      cytochemical detection of delta 5-3 beta-hydroxysteroid-dehidrogenase (HSD) were
      undertaken. An ultrastructural study was also performed. In our culture
      conditions, the timing of differentiation of both Sertoli and Leydig cells was
      similar to that in the fetus. Although mesonephros is required for seminiferous
      cord formation, differentiation of Sertoli and Leydig cells proceeds in its
      absence at 11.5 dpc. Moreover, when 3H-thymidine labeled mesonephroi were grafted
      to unlabeled gonads, endothelial and peritubular myoid-like cells migrated into
      the gonad. We propose that these cells might be the mesonephric cells required
      for seminiferous cord formation.

PMID- 8292536
TI  - Polar ionic currents around embryos of Lymnaea stagnalis during gastrulation and
      organogenesis.
AB  - Embryos of Lymnaea stagnalis generate ionic currents which can be measured with
      the vibrating probe. Here we investigated the presence and origin of the currents
      during late embryonic development. During gastrulation the current pattern
      correlates with the animal-vegetal polarity and during organogenesis it is
      correlated to the newly formed antero-posterior axis. The origin of the ionic
      currents was studied by inhibition of the Na+/K(+)-pump with ouabain and by
      enzyme-cytochemical detection of the Ca(2+)-pump. Ouabain treatment resulted in a
      reduced current density around the embryo, indicating that the Na+/K(+)-pump
      contributes significantly to the net current. The Ca(2+)-pump was found to be
      localized in the vegetal blastomeres during gastrulation and in the larval kidney
      during organogenesis. It seems likely that this Ca(2+)-pump renders only a minor
      contribution to the net current in late embryonic development. Ionic currents
      have now been described in Lymnaea from the uncleaved egg up to the juvenile
      snail. During this period the overall current pattern changes only twice,
      demonstrating that the voltage gradient generated by the embryo remains stable
      during prolonged periods in development.

PMID- 8292537
TI  - Early changes in embryonic nuclei fused to chemically enucleated mouse oocytes.
AB  - Mouse oocytes were chemically enucleated by subjecting them to etoposide and
      cycloheximide treatment during the first meiotic division (Fulka, Jr. and Moor,
      Mol. Reprod. Dev. 34:427-430, 1993) and thereafter electrofused to karyoplasts
      prepared from: (i) two-cell stage embryos at the G2-phase; (ii) four-cell stage
      blastomeres (S- or G2-phase); or (iii) embryonic stem (ES) cells. In the first
      series of experiments we used fusion conditions which do not induce egg
      activation to define the series of nuclear changes that are initiated immediately
      following fusion. Although fusion is evident within 5-10 min of induction, nuclei
      remain visible for up to 20 min prior to chromatin condensation and the formation
      of metaphase plates (60-90 min post fusion). After activation, the anaphase
      telophase transition is completed within 1-2 h, followed thereafter by cleavage
      of 75% of reconstituted eggs into two equal nucleated blastomeres, irrespective
      of the origin of the nuclei used for fusion. We conclude from the first study
      that a protocol involving fusion without activation, followed 90 min later by
      activation, is likely to be optimal for nuclear transplantation using MII-phase
      cytoplasts. In the second series of experiments the above optimized protocol was
      used to study the effects of different cell cycle combinations on chromosome
      organization in eggs reconstituted by nuclear transplantation. Both G1- and S
      phase karyoplasts fused to MII-phase cytoplasts exhibited spindle abnormalities
      in all eggs studied. Characteristic abnormalities in these cell cycle
      combinations included chromatin fragmentation and joining or aggregations of
      chromatin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292538
TI  - Cytochalasin-D treatment triggers premature apoptosis of insect ovarian follicle
      and nurse cells.
AB  - Follicle and nurse cells of developing lepidopteran ovarian follicles are
      eliminated after oocyte maturation. The process of disintegration of both cell
      types can be triggered prematurely in the follicle development by in vivo or in
      vitro treatment with a selective anti-actin agent cytochalasin D. Morphological
      changes observed in both follicle and nurse cells after cytochalasin D
      administration at the light and electron microscopy levels reveal all the
      characteristic morphological markers of a process called apoptosis, or programmed
      cell death. These changes include detachment of affected cells from basal lamina,
      loss of microvilli, crowding of structurally intact organelles, condensation of
      cytoplasm, nuclear shrinkage and fragmentation, and chromatin condensation.
      Examination of genomic DNA isolated from cytochalasin D affected cells revealed
      internucleosomal DNA fragmentation--a major biochemical hallmark of apoptosis.
      Experiments involving administration of actinomycin D or cycloheximide,
      respectively, indicate that the cell death of follicle and nurse cells triggered
      by cytochalasin D action does not require new RNA and/or protein synthesis.
      Possible mechanisms by which cytochalasin D could initiate the lethal biochemical
      pathway of programmed cell death in both cell types are discussed.

PMID- 8292539
TI  - The distribution of epidermal growth factor binding sites in the developing mouse
      palate.
AB  - The distribution of epidermal growth factor (EGF) receptors in the developing
      mouse palate was mapped using 125I-EGF labeling of paired palate organ cultures.
      125I-EGF binding sites were localized throughout the palate mesenchyme except in
      a region immediately adjacent to the midline seam. The EGF receptor was detected
      in all palatal epithelia at the beginning of culture, but as seam formation and
      subsequent degeneration took place it was down-regulated in the medial edge
      epithelia. Using submerged culture the mechanism of this down-regulation was
      investigated by treating with various growth factors such as EGF, basic
      fibroblast growth factor (bFGF), insulin-like growth factor-II (IGF-II) and
      transforming growth factors alpha and beta (TGF-alpha, TGF-beta). Conventional
      Trowell organ culture was not used because it was observed that the Millipore
      filter blocked growth factor uptake. All three TGF-beta isoforms accelerated
      palate fusion and TGF-beta 1 reduced 125I-EGF binding throughout the palate,
      suggesting a potential level of regulation during palatogenesis. Contrary to
      previous reports, EGF treatment in the absence of serum prevented palatal shelf
      fusion, and also down-regulated subsequent 125I-EGF binding.

PMID- 8292540
TI  - Mechanism of closure of experimental excision-wounds in the bare upper layer of
      the chick blastoderm.
AB  - The closure of experimental excision-wounds in the upper layer of the
      gastrulating chick blastoderm was studied by time-lapse videography and
      videomicrography and by light microscopy, transmission electron microscopy and
      scanning electron microscopy. One experimental excision-wound was made in the
      upper layer of stages 4V to 6V blastoderms (Vakaet, Arch. Biol. (Liege) 81:387
      426, 1970), in the proamnion where no middle layer cells are present. The deep
      layer was previously discarded, so that the wounds were made in the bare upper
      layer. They closed within 2 to 6 hours and further development was normal by in
      vitro standards. With videography, global movements of the upper layer towards
      the wound were observed. With videomicrography, the wound submarginal region
      cells were seen to move like sheep in a flock: individual cells in different
      directions, the whole flock towards the wound. During closure the shape of the
      wound edge was irregular. The structure of the epithelium of the wound
      submarginal region was unchanged throughout closure: a pseudostratified columnar
      epithelium in which cell divisions occur at its dorsal side and are parallel to
      its surface. The basal lamina was absent below the edge of the wounds. We propose
      that the cells of the upper layer are mobile against one another and are not
      confined to a specific part of the basal lamina. During wound closure the
      movements of the cells on the basal lamina would be driven by mitotic pressure.
      This is the horizontal pressure exerted by the addition of daughter cells and
      their parting during anaphase and telophase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292541
TI  - The influence of thyroid hormones on the growth of the lungs in perinatal rats.
AB  - The growth and rates of protein turnover in the perinatal lung have been studied
      in the rat during normal development between late gestation and weaning, and
      after altering their thyroid status. The aim was to establish what influence
      thyroid hormones have on the early stages of growth in the lungs. Perinatal
      hypothyroidism was induced by administering propylthiouracil (PTU) via the
      mothers' drinking water from late gestation and throughout lactation. A
      precocious and elevated surge of thyroid hormones was induced by daily injections
      of T4 from day 3 postpartum onwards. Hypothyroidism in the neonate, but not the
      fetus, significantly retarded the growth of the animal and its lungs. This was
      attributable to a decrease in both the pulmonary rates of protein synthesis and
      protein degradation; the effect on the former rate exceeding that on the latter.
      Neonatal hyperthyroidism did not significantly alter protein turnover or the
      growth of the lungs, compared with euthyroid control tissues. This contrasts with
      the accelerated growth of some other body tissues in the presence of excess
      thyroid hormones.

PMID- 8292542
TI  - The processing of macronuclear DNA sequences during macronuclear development of
      the hypotrichous ciliate Stylonychia lemnae.
AB  - The organization of two macronuclear DNA sequences in the polytene chromosomes of
      the hypotrichous ciliate Stylonychia lemnae and their processing from the
      micronucleus via the polytene chromosome stage up to the macronucleus was
      analyzed. The overall organization of these sequences in the polytene chromosomes
      resembles that described for the micronucleus of other hypotrichous ciliates,
      i.e. they are interrupted by internal eliminated sequences and not associated
      with telomeric sequences. The spacer region between the genes is bordered by
      direct repeats and inverted repeats are found at the termini of macronuclear
      sequences and in the spacer region. The organization of these macronuclear DNA
      sequences in the micronucleus was analyzed by polymerase chain reactions. The
      results obtained show that in the sequences analyzed no DNA reorganization occurs
      during polytene chromosome formation.

PMID- 8292543
TI  - Development of hatchability in halibut (Hippoglossus hippoglossus) embryos.
AB  - Halibut (Hippoglossus hippoglossus) eggs raised in darkness hatched between days
      14.5 and 16 after fertilization. Eggs incubated in white light (3.2
      microE/sr1/m2) remained unhatched, so that time of intra ovo development could be
      doubled. Photo-arrest of hatching was non-diapausal since embryonic growth
      continued. Transfer of photo-arrested eggs to darkness induced rapid and
      synchronous hatching. This procedure allowed analysis of development of
      hatchability. Hatching was not observed prior to day 14. Nonsynchronous hatching
      over three days was seen when eggs were induced on day 14 + 1 h, or on day 14 + 9
      h. However, darkness-induction on day 14 + 22 h produced synchronous hatching
      within 140 min. This high rate of inducibility persisted until day 18, before
      declining slowly. Hatching-induction was not observed beyond day 22. Low
      hatchability in long-term photo-arrested embryos apparently reflects a loss of
      the anatomical prerequisites for the rim-hatching mechanism. Altered hatchability
      and morphogenesis after prolonged intra ovo development indicate that hatching in
      halibut is possible only at an early, defined ontogenetic stage.

PMID- 8292544
TI  - Expression and immunohistochemical localization of laminin and type IV collagen
      in developing human fetal tracheal glands.
AB  - The expression and distribution of laminin and type IV collagen, two major
      components of the basement membrane, were investigated at the epithelio
      mesenchymal interface of the human developing tracheal glands from 10 to 37 weeks
      of gestation. The localization of these molecules was assessed by indirect
      immunoperoxidase and indirect immunofluorescence staining and correlated to
      morphogenesis and epithelial cell differentiation. Laminin and type IV collagen
      were detected as early as 10 weeks of gestation in a continuous, linear pattern
      in the basement membrane surrounding the epithelial tracheal tube. By 12 weeks of
      gestation the basement membrane developed large openings at the tips of the
      budding glands beneath poorly differentiated cells, concomitant with the onset of
      morphogenetic movements. The remodeling of the basement membrane led to branching
      epithelial morphogenesis. The maturation and the functional differentiation of
      the secretory cells appeared later in the epithelium, when the basement membrane
      was strongly labeled with both anti-laminin and anti-type IV collagen antibodies,
      after 24 weeks of gestation. At this time the basement membrane became regular
      and thick and the maturation of serous cells increased progressively. These
      results suggest that the remodeling of the basement membrane takes place very
      early during gestation and that the morphogenesis and the maturation of the
      tracheal glands are rapidly achieved in humans.

PMID- 8292545
TI  - Pupils' perceptions of a good teacher: a developmental perspective from Trinidad
      and Tobago.
AB  - The study reports on a large-scale survey of pupils' perceptions of a good
      teacher in the Caribbean republic of Trinidad and Tobago. An essay-based,
      interpretive mode of research was used to elicit and identify constructs used by
      pupils between ages 7 and 17. The sample was a proportional, stratified,
      clustered, yet randomly selected representation of primary and secondary schools
      across the two islands. 1633 essays were content analysed and coded for age
      developmental comparison. Factor analysis showed no consistent underlying
      groupings of the 166 conceptual items by age, thus analysis was undertaken within
      logically constructed sets of items that are described: physical and personal
      characteristics of the teacher, quality of the relationship between teacher and
      pupil, control of behaviour by teacher, descriptions of the teaching process, and
      expected educational and other outcomes obtained by pupils due to teacher
      efforts. Results showed a general increase in number of conceptual items (and
      words per essay) by age, but this confuses four further criteria of item used.
      The four criteria were: age constancy, characteristics of younger pupils,
      characteristics of 11-13 year-olds, and characteristics of the oldest pupils. All
      ages perceived good teachers by physical presentation (clothing and appearance),
      teachers' care for pupils, descriptive teaching actions, and trustworthiness.
      Younger pupils focused on appearance, subjects taught, and assertion of physical
      punishment. Mid-aged pupils focused on the range of classroom control used by
      teachers (including distributive and retributive punishments), actions involved
      in the teaching process, and a growing awareness of the individual needs of
      pupils. Oldest pupils understood that good teachers must be well trained and
      highly motivated, should be sensitive and responsive to the needs of pupils, draw
      the pupils into the learning process, and have a major responsibility in
      preparing the pupil for the world of work and further education. Important
      aspects of the study show the link between pupils' conceptual reality and
      classroom environment, that pupils are very concerned about the relationship
      between themselves and teachers, and that the curriculum dominated approach to
      teaching does not meet pupil expectations.

PMID- 8292546
TI  - Young children's representations and strategies for subtraction.
AB  - This is a report of a study of the representations and strategies for
      subtraction, used by a sample of 55 children in years 1, 2 and 3 in three
      suburban schools in low, medium and high socio-economic areas of Brisbane. Each
      child was interviewed and videotaped individually early and late in the year. In
      order to determine what representations and strategies they would choose to use
      they were presented with operations represented in symbols and asked to explain
      their procedures as they worked. The teachers were also interviewed to determine
      the representations that they were introducing. The general development sequence
      was from use of objects, to use of counting to mental calculations using
      knowledge of number facts and place value. Written algorithms, with or without
      concrete materials, were used very little despite the fact that they were being
      taught in years 2 and 3. The results are discussed from the perspective of the
      demand that the procedures make on children's information processing capacity and
      the possibility that some of the difficulties occur because teachers introduce
      procedures that are recommended in curriculum documents, without being aware of
      the cognitive load that they impose.

PMID- 8292547
TI  - Person-environment fit: using commensurate scales to predict student stress.
AB  - The relationship between person-environment fit and stress was examined for two
      samples of university students (N = 55 and 79). The Kirton Adaption-Innovation
      Inventory (KAI) was modified to assess the students' perceptions of the adaptor
      innovator style required by their course, the styles they exhibited in the
      course, and their ideal style preferences. To ascertain fit, the KAI total scores
      and subscale scores (Originality, Efficiency, and Rule/Group Conformity) were
      used to classify students on three dimensions: (1) perception of what style their
      course required, adaptive or innovative; (2) congruence between the style the
      course required and the style they exhibited in the course; and (3) the magnitude
      of the difference, if any, between the required style and the exhibited style.
      Points two and three are measures of fit. The dependent variable was stress. Also
      the students' ideal style scores, KAI total and subscales, were substituted for
      the exhibited scores and the classification and analyses were repeated. Analysis
      of the total scores revealed that a course requiring adaptive behaviours was
      perceived as more stressful than a course requiring innovative behaviours.
      Similarly, an analysis of the Rule/Group Conformity scores revealed that the
      greater the conformity required the greater the stress. Also the less originality
      demanded in the course the greater was the perceived stress. For the KAI total
      scores and Rule/Group Conformity scores, the two measures of fit (incongruity and
      magnitude of the incongruity) were not related to stress. However, analyses of
      the Originality and Efficiency subscales supported the importance of the P-E fit
      position. For both subscales, stress was associated with the magnitude of the
      difference between what was required in the course and what students exhibited in
      the course. Educational implications derived from these findings as well as
      recommendations for future research are discussed.

PMID- 8292548
TI  - Characteristics of self-worth protection in achievement behaviour.
AB  - Two experiments are reported comprising an investigation of individual difference
      variables associated with self-worth protection. This is a phenomenon whereby
      students in achievement situations adopt one of a number of strategies, including
      withdrawing effort, in order to avoid damage to self-esteem which results from
      attributing failure to inability. Experiment 1 confirmed the adequacy of an
      operational definition which identified self-worth students on the basis of two
      criteria. These were deteriorated performance following failure, together with
      subsequent enhanced performance following a face-saving excuse allowing students
      to explain failure without implicating low ability. The results of Experiment 2
      established that the behaviour of self-worth protective students in achievement
      situations may be understood in terms of their low academic self-esteem coupled
      with uncertainty about their level of global self-esteem. Investigation of the
      manner in which self-worth students explain success and failure outcomes failed
      to demonstrate a tendency to internalise failure but revealed a propensity on the
      part of these students to reject due credit for their successes. The implications
      of these findings in terms of the prevention and modification of self-worth
      protective reactions in achievement situations are discussed.

PMID- 8292550
TI  - Children's understanding of number words.
AB  - This research notes gives details of an atypical response to a 'give a number'
      task by a 34-month-old child. The child clearly demonstrated that he understood
      the word 'two' to refer to an object rather than to a quantity. This incident
      offers support to Fuson's (1988) theory of the functionally specific initial
      acquisition of number word meanings and suggests that Gelman & Meck's (1983)
      'principles first' account of the development of counting gives insufficient
      weight to the role of language and social interaction in the development of early
      number understanding. The incident also shows that our knowledge of this area of
      development would benefit from a greater emphasis on longitudinal studies,
      studies of social context and studies of individual differences in the processes
      of acquisition.

PMID- 8292549
TI  - A factor analytic study of teachers' perception of pupils' undesirable
      behaviours: a rejoinder to Langfeldt (1992).
AB  - This study investigates the effects of teacher sex and pupil sex in the teachers'
      perception of the seriousness of three extracted patterns of pupils' undesirable
      behaviours. In contraposition to Langfeldt's (1992) conclusion that gender
      differences are no longer observable when investigating complex patterns of
      behaviour as opposed to single behavioural items the present writers argue that
      where gender is a true effect this will also be evident at a factorial level of
      abstraction. A sample of 844 primary school teachers in Malta rated the
      seriousness of 16 selected undesirable behaviours when these are manifest in boy
      pupils and in girl pupils. A principal components analysis revealed three
      patterns of perceived problem behaviours labelled 'withdrawal behaviour',
      'dissocial/overtly challenging behaviour' and 'disruptive behaviour'. Gender
      differences were found in each of the three factors: the main effect pupil sex
      was significant on 'withdrawal behaviour' and 'disruptive behaviour', and teacher
      sex on 'dissocial/overtly challenging behaviour'. Results also indicated a
      significant interaction effect involving teacher sex and pupil sex on the factor
      'withdrawal behaviour'.

PMID- 8292551
TI  - Healthy children's understanding of their blood: implications for explaining
      leukaemia to children.
AB  - Explanations of leukaemia to children usually include details of blood function
      and structure. In study 1, 3-year-olds (N = 25), 4-year-olds (N = 25), and 8-year
      olds (N = 27) were interviewed about their understanding of the properties of
      blood and any occasions when they remembered seeing blood. They were also asked
      whether other animals and objects had blood or not, and to give reasons for this.
      Children justified their decisions in three ways: only people have blood, they
      had seen blood on a particular occasion, or only creatures which shared a human
      property (walking or talking) could have blood. In study 2, an intervention to
      increase children's understanding of the function of different blood cells is
      reported. It was partially successful. Children who reported an incident in which
      they saw blood were more likely to recall information about the function of red
      cells, white cells and platelets compared with children who did not report a
      previous experience (p < .001). In terms of explaining leukaemia to a child, we
      conclude that explanations should build on previous experience, and not be based
      simply on chronological age.

PMID- 8292552
TI  - Ultrastructure of calcified muscle fibres at the implantation site of
      demineralized bone matrix gelatin.
AB  - To clarify the mechanism of calcification during new bone formation induced by
      demineralized bone matrix gelatin (BMG), BMG was implanted into the skeletal
      muscle of Sprague-Dawley (SD) rats and histological changes were examined
      1,2,3,5,7 and 10 days later. From day 2 after implantation, calcification was
      observed in muscle fibres near the implanted BMG. Calcification of the BMG
      ('acellular mineral deposition') was first seen on day 3 and in both,
      calcification increased. The calcification of muscle fibre was first seen in the
      sarcoplasmic reticulum (SR) and then in mitochondria or lipid droplet-like
      structures of satellite cells. The muscle mineral deposition occurred without
      osteogenic cells and matrix vesicles in the same way as 'acellular mineral
      deposition'.

PMID- 8292553
TI  - Suppression of development of anti-nuclear antibody and glomerulonephritis in NZB
      x NZWF1 mice by persistent infection with lactic dehydrogenase virus: possible
      involvement of superoxide anion as a progressive effector.
AB  - The development of anti-nuclear antibody (ANA) and glomerulonephritis (GN) in
      autoimmune NZB x NZWF1 mice was suppressed by persistent lactic dehydrogenase
      virus (LDV) infection. This observation was used to study a possible pathogenetic
      role for the toxic oxygen radical, superoxide anion (O2-), in the progression of
      ANA and GN. Compared to macrophages from NZB x NZWF1 mice with LDV infection,
      macrophages from uninfected NZB x NZWF1 mice exhibited an age-related and drastic
      increase in O2- production in association with the development of the ANA and GN
      (representing the late stage of disease). NZB x NZWF1 mice with or without LDV
      infection were then given the O2- scavenger superoxide dismutase (SOD) during the
      late stage of the disease. Treatment of uninfected NZB x NZWF1 mice with SOD
      (10,000 units/mouse/day for 3 weeks) protected animals from the development of
      ANA and GN. SOD treatment also suppressed the development of the lesions in NZB x
      NZWF1 mice with LDV infection. Our findings suggest that O2- may, at least in
      part, contribute to the development of ANA and GN in the late stage of disease,
      and that decreased O2- production in NZB x NZWF1 mice with LDV infection may be
      responsible for the suppression of the development of ANA and GN in the late
      stage of the disease.

PMID- 8292554
TI  - A temporal study of the lesions induced by MoMuSV-349.
AB  - We used time point studies to document the progression of neoplasms, haematologic
      abnormalities and associated lesions induced by Moloney murine sarcoma virus-349
      (MoMuSV-349). BALB/c mice inoculated intraperitoneally with MoMuSV-349 first
      developed histologically discernible lesions at 14 days post-inoculation
      (d.p.i.). The initial neoplasms were characterized by whorls of fusiform or
      spindle-shaped cells enmeshing dense infiltrates of neutrophils and macrophages.
      By 21 d.p.i., clinical signs associated with MoMuSV-349 infection were evident.
      The distribution of the neoplasms was more widespread, although the histologic
      appearance of the tumours was very similar to that found at 14 d.p.i. All mice
      sacrificed at 28 d.p.i. exhibited characteristic clinical signs associated with
      MoMuSV-349, including moderate cachexia. Histologically, neoplasms observed at 28
      d.p.i. contained a significant vascular component. By 35 d.p.i., all mice
      exhibited severe clinical signs (e.g. cachexia, dull hair coat, uneven gait).
      Histologically, all the neoplasms had a predominant vascular component. Non
      neoplastic lesions, such as severe thymic atrophy and multifocal pulmonary
      haemorrhage, were commonly present. Mice sacrificed 42 d.p.i. were clinically,
      grossly and histologically similar to those sacrificed at 35 d.p.i. However, one
      difference found in the 42 d.p.i. group was the presence of rare
      rhabdomyosarcomas infiltrating the skeletal muscles. Mice inoculated with MoMuSV
      349 developed severe neutrophilia and lymphopenia, and moderate anaemia. This
      study demonstrates that MoMuSV-349 induced angiosarcomatous neoplasms are
      characterized by stage development and severe haematologic and non-neoplastic
      abnormalities.

PMID- 8292555
TI  - A murine model of experimental autoimmune lens-induced uveitis using Klebsiella
      O3 lipopolysaccharide as a potent immunological adjuvant.
AB  - Experimental autoimmune uveitis and finally panophthalmitis could be produced in
      mice by repeated immunization of syngeneic eyeball extract mixed with Klebsiella
      O3 lipopolysaccharide (KO3 LPS) as a powerful immunological adjuvant. No ocular
      lesions were produced in mice given eyeball extract emulsified in complete
      Freund's adjuvant (CFA), KO3 LPS alone or eyeball extract alone.
      Histopathological changes in the ocular lesions at the early stage after the
      second or tertiary immunization were characterized by infiltration with
      inflammatory cells in the ciliary body and iris. The iridocyclitis was followed
      by extensive infiltration of polymorphonuclear leucocytes (PMN) into the cornea,
      lens and the surrounding tissues after repeated immunization. Finally, these
      areas were replaced by granulomatous tissues infiltrated with mononuclear cells.
      On the other hand, the structure of the retina and sclera was partially
      preserved. Those mice exhibited production of autoantibodies and development of
      the delayed-type hypersensitivity (DTH) to syngeneic eyeball extract. Moreover,
      ocular lesions could be produced in normal recipient mice by transfer of
      sensitized lymphocytes from hyperimmunized mice. Therefore, it was suggested that
      the ocular lesions produced by repeated immunization with the mixture of eyeball
      extract and KO3 LPS were due to the autoimmune mechanism. This might be useful to
      model immunological phenomena in the pathogenesis of human phacoantigenic
      uveitis.

PMID- 8292556
TI  - Collagen content of uninjured skin and scar tissue in foetal and adult sheep.
AB  - Total collagen content (measured as hydroxyproline) and Type I/Type III ratio
      (measured by SDS-PAGE) of normal skin and of scar tissue developing within a
      subcutaneously implanted polyvinyl sponge have been determined in 75, 90 and 120
      day foetal lambs and adult sheep and correlated with histological appearances of
      the same tissues. Collagen content of normal skin is low at 75 days and rises
      progressively until birth when it is about half the adult level. The proportion
      of Type III in normal skin is highest at 75 days and falls progressively as the
      foetus develops. With implanted sponges the time course of changes in collagen
      content and I/III ratio are similar in all foetal groups and in adult sheep.
      Collagen content is low 3 days after implantation and rises progressively to
      reach a similar level in all groups by 28 days. The levels correlate closely with
      the amount of collagen visible in histological sections. The proportion of Type
      III is highest at 3 days in all groups and falls progressively as the newly
      formed tissue matures. The findings confirm our previous study of the healing of
      skin wounds that form as early as 75 days gestation foetal lambs can form scar
      tissue in a similar way to adult sheep.

PMID- 8292557
TI  - Enteric vascular endothelial response to bacterial endotoxin.
AB  - The response of enteric vasculature to endotoxin was examined at the
      ultrastructural level using a murine model of endotoxin-induced acute diarrhoea.
      Morphological changes indicative of endothelial damage were evident as early as
      15 minutes following endotoxin challenge. These changes, characterized by
      widening of intercellular spaces, increased microvillous projections and the
      appearance of stress fibres, preceded the leucocytic response. Endothelial damage
      increased with time, being associated with progressive degenerative changes in
      the plasma membrane, cytoplasm and organelles, ultimately leading to
      desquamation. These latter changes were temporally associated with margination of
      neutrophils and platelet adhesion to the denuded subendothelium. The venules were
      the primary site of these changes while the capillaries were the least affected.
      The arterioles were markedly constricted with minimal endothelial damage. These
      changes suggest that the enteric vascular endothelium may be an important target
      organ, and the resultant endothelial injury may have implications in host
      responses to endotoxin.

PMID- 8292558
TI  - Continued platelet interaction with de-endothelialized aortae associated with
      slower re-endothelialization and more extensive intimal hyperplasia in
      spontaneously diabetic BB Wistar rats.
AB  - Diabetic patients are at increased risk for atherosclerosis and its
      complications. Platelets contribute to atherosclerosis through effects of factors
      released from platelets which interact with injured vessels. Diabetic platelets
      are hypersensitive to agonists in vitro. If diabetic platelets interact more
      extensively with injured vessels, they could contribute to increased vascular
      disease in diabetic patients. We examined the effect of spontaneous diabetes in
      BB Wistar rats on platelet accumulation and turnover, endothelial regeneration
      and intimal thickening in rat aortae de-endothelialized with a balloon catheter.
      51Cr-labelled platelets were injected before or at different times after injury,
      and platelet accumulation on the aortae was determined at various times after the
      injection. Platelets rapidly accumulate on the aortae 30 min after injury and the
      net accumulation is similar in control and diabetic rats. Platelets continue to
      interact to a similar extent with the aortae of control and diabetic rats up to 4
      days after injury, but the extent of interaction is less than that observed
      initially after injury. After 4 days, aortae of control rats gradually lose their
      ability to attract new platelets; this phase is delayed in diabetic rats. When
      51Cr-platelets are injected 6 days after injury more radioactivity accumulates in
      a 24-h period on aortae of diabetic (22,050 +/- 6290 plts/mm2) than of control
      rats (8030 +/- 670 plts/mm2, P < 0.05). Seven days after injury, the percentage
      of aortic re-endothelialization is less in diabetic (58.2 +/- 7.2) than in
      control rats (86.8 +/- 6.9, P < 0.01). By 28 days, re-endothelialization is
      complete in control and diabetic rats. The smooth-muscle-cell-rich neointima is
      thicker and more extensive in diabetic than in control rats 15 or 28 days after
      aortic injury. Diabetes in rats is associated with continued platelet interaction
      with de-endothelialized aortae, slower re-endothelialization, and the formation
      of a thicker and more extensive smooth-muscle-cell-rich neointima.

PMID- 8292561
TI  - Posttraumatic stress disorder among battered women: risk and resiliency factors.
AB  - This study proposed that diagnosable levels of PTSD would be found among battered
      women and that the level of exposure to violence in the battering relationship
      would be an important contributing factor to the development of PTSD while other
      pre-trauma and post-trauma variables such as social support, intercurrent life
      events, religiosity, and developmental family stressors would also be related to
      PTSD symptom levels. Fifty-three battered women were given standardized self
      report measures to assess these variables. As hypothesized, a significant
      proportion of battered women in the sample were diagnosed as PTSD positive.
      Multiple regression analyses revealed that violence exposure severity, recency of
      the last abusive episode, social support, intercurrent life events, intrinsic
      religiosity, and developmental family stressors predicted 43% of the variance in
      PTSD symptomatology.

PMID- 8292560
TI  - New histological observations in spontaneously developing osteoarthritis in the
      STR/ORT mouse questioning its acceptability as a model of human osteoarthritis.
AB  - Naturally developing spontaneous osteoarthritis (OA) is seen in a number of small
      animals one of which is the STR/ORT mouse, an accepted model of human OA. A
      histological evaluation of the patello-femoral joints of 37 male STR/ORT mice has
      shown features that are inconsistent with the disease in human joints. These
      include the presence of a prominent acute and chronic synovial inflammatory
      infiltrate. Such findings call into question the proposed aetiology of the
      arthropathy in this strain of mouse and its acceptability as a model of human
      primary OA.

PMID- 8292559
TI  - Cyclosporine-induced nephrotoxicity in deoxycorticosterone-NaCl treated rats.
AB  - This study tested the hypothesis that the adverse effects of cyclosporine (Cy)
      are accelerated in animals with induced hypertension. Four groups of rats were
      unilaterally nephrectomized at 5 weeks of age. Two weeks later, two of these
      groups received implantations of Silastic strips impregnated with
      deoxycorticosterone acetate (DOCA) and were maintained on 1% saline (DOCA-NaCl);
      the other two groups served as sham controls. Daily injections of Cy (20 mg/kg)
      were given to one DOCA-NaCl and one control group. During the initial 3 days, the
      Cy/DOCA-NaCl treated rats displayed a significant increase in systolic arterial
      pressure (SAP), but their SAP did not increase significantly thereafter. Cy/DOCA
      NaCl treatment caused severe nephrotoxicity 18 days after initiation of
      treatment, but neither cyclosporine nor DOCA-NaCl treatment alone resulted in
      morphological renal damage. In Cy/DOCA-NaCl rats, the interstitial spaces between
      renal tubules were dramatically increased in size and contained abundant bundles
      of collagenous fibres, deposits of immunoreactive laminin, and infiltrates of
      mononuclear cells. In a second experiment, bilateral renal denervation prior to
      treatment did not lessen the Cy-induced renal damage. These results indicate that
      in the DOCA-NaCl rat, Cy treatment damages the renal cortex in a pattern similar
      to that observed in humans treated chronically with Cy. Further, the results
      indicate that an absence of renal innervation does not decrease the nephrotoxic
      effects of Cy in this rapid onset model.

PMID- 8292562
TI  - For better or worse: the case of marital rape.
AB  - The small amount of literature on marital rape compared to the rather large
      amount of literature on stranger rape suggests that the former is viewed as a
      less serious crime. This conclusion is supported, in part, by the way marital
      rape is minimized by the law. This paper is a review of the existing literature
      on marital rape. It combines the material on the history of marital rape, the
      legal issues involved with marital rape, when marital rape is likely to occur,
      the effects of marital rape, and societal views of the marital rape victim in a
      single comprehensive paper. The intent is to provide a synthesized examination of
      marital rape, as well as to encourage research on marital rape. It is concluded
      that marital rape is a pressing problem that tends to be minimized by society and
      researchers need to devote greater attention to marital rape issues.

PMID- 8292563
TI  - Spousal homicide risk and estrangement.
AB  - Frequencies of homicide victimization of wives and husbands, while cohabiting and
      when separated, are reported for all spousal homicides known to the police in
      Canada (1974-1990), in New South Wales, Australia (1968-1986), and in Chicago
      (1965-1990). In all three data sets, the degree to which spousal homicide
      victimization was female-biased was significantly greater when the couple were
      estranged than when they were coresiding. Victim counts and population-at-large
      estimates of coresiding and separated now-married spouses were combined to
      estimate differential homicide rates incurred by coresiding and estranged married
      persons. Wives in all three countries incurred substantially elevated risk when
      separated as compared to when coresiding.

PMID- 8292564
TI  - An exploration of the violent victim experiences of female offenders.
AB  - Female offenders are often portrayed as victims of violence, yet few studies have
      systematically examined such victimization. Violent experiences may both
      contribute to, and result from, crime--early family abuse may help propel a young
      woman into crime, and a criminal lifestyle may increase her risk of assault by
      strangers and intimate partners. Using data from 83 inmates, this study examined
      violent childhood and adult experiences, and explored possible linkages between
      victimization and offending. Although many women reported violent experiences,
      most striking was the high rate of assault by intimate partners. Early physical
      abuse was associated with earlier entry into crime, and with more diverse
      criminal activity. Attacks by strangers were more often reported by women who
      engaged in more frequent and diverse criminal activity. The data suggest that in
      order to understand female crime, additional research on the complex
      relationships between offending and victimization is warranted.

PMID- 8292565
TI  - Mental disorders in battered women: an empirical study.
AB  - Prevalence of mental disorders in 62 battered women receiving services from a
      Florida battered woman agency was identified by means of a structured interview,
      the Diagnostic Interview Schedule. Of the total sample of battered women, 30 were
      in a shelter operated by the agency and 32 were living in their own homes and
      receiving assistance from the agency. Resultant diagnoses met diagnostic criteria
      developed in the Diagnostic and Statistical Manual (3rd. ed.) of the American
      Psychiatric Association. The Diagnostic Interview Schedule is a 263 item
      structured interview used in the National Institute of Mental Health
      Epidemiological Catchment Area program carried out in the early 1980s. The
      Diagnostic Interview Schedule permits the use of 10,953 females in the
      epidemiological study as a comparison group of normal women. Scoring of the
      interviews was done by a computer diagnostic program with absolute decision
      rules. Extremely high prevalence was found for psychosexual dysfunction, major
      depression, post traumatic stress disorder, generalized anxiety disorder, and
      obsessive compulsive disorder. These diagnoses appear to reflect the major
      components of the battered woman syndrome developed by Lenore Walker and the
      study approximates Walker's request for improved methodology in the research into
      the psychology of the battered woman.

PMID- 8292566
TI  - Justice for victims of spouse abuse in divorce and child custody cases.
AB  - Unequal power positions and domination-subordination roles of battering husbands
      and battered wives during marriage contaminate the process of separation and
      divorce. These dynamics may continue long after the marriages cease. Risks of
      extreme violence, rape, and homicide are highest when victims seek freedom.
      Because both victims and abusers construct a veil of secrecy while married, even
      if abused wives disclose the violence during the separation process, there may be
      nothing to substantiate their claims. Restraining orders often fail to restrain
      obsessed husbands; other husbands may get revenge by using their children as
      pawns. Attitudes favoring fathers' rights and joint custody may help win unfair
      financial advantages, and/or continued control over victims after divorce.
      Mandatory mediation in some states may give abusers additional advantages.
      Although some of these problems are being addressed with mechanisms to ameliorate
      them, the need to recognize problems facing battered wives in divorce and custody
      contexts has not received adequate attention. The purpose of this article is to
      provide a review and commentary on these issues.

PMID- 8292567
TI  - Venous gas embolism associated with argon-enhanced coagulation of the liver.
AB  - Argon-enhanced coagulation (AEC) is a method for operative coagulation of tissues
      that utilizes a jet of argon gas encompassing an electrofulguration arc. Concern
      has been raised that the argon jet may produce harmful venous gas embolization.
      Two questions were addressed by this study. First, does AEC result in generation
      of venous gas emboli, and if so, what is the influence of gas flow rate and
      coagulation power on the amount of gas emboli generated? Second, does the amount
      of venous gas emboli generated by AEC produce harmful hemodynamic effects? Two
      AEC units were evaluated during coagulation of cut sections of the liver in pigs.
      The number of gas emboli generated was measured by an ultrasonic Doppler flow
      cuff placed around the caudal vena cava. Hemodynamic variables measured following
      AEC included systemic and pulmonary arterial pressure, pulmonary wedge pressure,
      and cardiac output by thermodilution. Venous gas emboli were produced during AEC
      of the liver. The number of gas emboli generated increased with increasing gas
      flow rates, but was not affected by coagulation power. No change in any of the
      measured hemodynamic variables was observed following AEC of the liver. The
      following recommendations were made: (1) Surgeons using AEC should select an
      argon flow rate as low as feasible to clear a bleeding tissue surface of blood
      and debris. (2) Although AEC seems to be associated with tolerable amounts of
      venous gas embolism, surgeons and anesthesiologists should be aware that the
      potential for harmful venous gas embolism exists. (3) In patients where extensive
      use of AEC is planned, appropriate monitoring and precautions for gas embolism
      should be undertaken.

PMID- 8292568
TI  - Calcium channel blockade in rats with cyclosporine-induced vasoconstriction.
AB  - Calcium channel blockade has been found to attenuate nephrotoxicity of
      cyclosporine. However, it is not known whether intrarenal vasoconstriction caused
      by cyclosporine is totally mediated by vascular smooth muscle calcium influx. To
      study the protective effects of two calcium blockers on cyclosporine-induced
      intrarenal vasoconstriction and renal microvascular blood flow, hydronephrotic
      rat kidneys were suspended in an environmentally controlled tissue bath. Renal
      microvessel diameters and microvascular blood flow were determined by in vivo
      videomicroscopy and Doppler velocimetry. Calcium channel blockade was achieved by
      adding verapamil hydrochloride (5.6 x 10(-5) M) or diltiazem hydrochloride (2.8 x
      10(-5) M) to the tissue bath, which respectively resulted in a 15 +/- 2% and 16
      +/- 3% interlobular arteriolar dilation, a 13 +/- 3% and 12 +/- 2% afferent
      arteriolar dilation, and a 60 +/- 8% and 46 +/- 14% increase in interlobular
      blood flow. When cyclosporine (1.7 x 10(-3) M) was added to the tissue bath,
      there was a constriction of the interlobular arterioles to 4 +/- 3% below
      baseline in rats receiving verapamil and 9 +/- 3% below baseline in rats
      receiving diltiazem. Microvascular blood flow was reduced by the addition of
      cyclosporine to 3 +/- 4% above original baseline values in the verapamil group
      and 22 +/- 6% below baseline in the diltiazem group. Afferent arterioles were
      similarly constricted by cyclosporine. The results indicate that calcium blockade
      causes preglomerular vasodilation and protects the microvascular blood flow
      induced by cyclosporine. Since verapamil or diltiazem did not prevent arteriolar
      constriction as observed when cyclosporine was added, it was concluded that the
      mechanism of acute cyclosporine-induced vasoconstriction is not solely mediated
      by vascular smooth muscle calcium influx through potential dependent channels.

PMID- 8292569
TI  - Lysosomal enzyme production at the interface surrounding loose and well-fixed
      cemented tibial hemiarthroplasties in the rabbit knee.
AB  - Fourteen mature New Zealand white female rabbits had a right, cemented, tibial
      hemiarthroplasty using a stemmed, fluted, titanium alloy, condylar-type
      prosthesis. In one group (seven rabbits), polymethyl methacrylate (PMMA) was used
      to cement the prosthesis firmly. In a second group (seven rabbits), the
      prosthesis was treated with cement ex vivo; the prosthesis and cured cement were
      then implanted, and rotated once within the bone to ensure that the prosthesis
      was loose fitting. Roentgenograms performed postoperatively and at 3 months were
      graded for new (i.e., not present on the immediate postoperative radiograph)
      radiolucent lines. At 3 months, the tissue adjacent to the implant was harvested
      sterilely and cultured over a 3-day period; the tissues and culture supernatants
      were then assayed for total protein, DNA content, and lysosomal enzyme activity
      (N-acetyl-beta-D-glucosaminidase and beta-glucuronidase). The mean cumulative
      grading of new lucent lines was 0.4 +/- 0.3 (mean +/- standard error) for the
      well-fixed prosthetic group and 2.0 +/- 0.6 for the loose prosthetic group. The
      tissue surrounding loose prostheses contained more DNA and total protein, and
      produced greater amounts of lysosomal enzymes compared to well-fixed prostheses.
      The control left sides were not statistically different for any parameter
      analyzed. The increased DNA content demonstrates an increase in cellularity of
      the tissue surrounding loose prostheses. Normalization of the relative amount of
      enzyme released as a function of cellularity (DNA) suggests that the influx of
      cells into the area surrounding loose prostheses may be more important to the
      overall increase in lysosomal enzyme release than increased production of
      lysosomal enzymes by individual cells.

PMID- 8292570
TI  - A surgical approach to chronic aortomyoplasty in the goat model.
AB  - The left latissimus dorsi skeletal muscle of seven male goats was prepared and
      applied circumferentially to the descending aorta just below the subclavian
      artery. Stimulation of the neural pedicle of the latissimus dorsi was performed
      in an attempt to convert it to a fatigue-resistant cardiac-like muscle. Timing of
      the stimulus was in diastole. Biochemical assays established the conversion, and
      echocardiography demonstrated aortic compressions in the area of the muscle wrap.
      Although limited in numbers, the converted latissimus dorsi muscle in the extra
      aortic position appears to provide diastolic augmentation.

PMID- 8292571
TI  - A surgical technique for bilateral cochleotomy in the Long-Evans rat.
AB  - A bilateral cochleotomized surgical rat model, needed for a study involving
      microwave effects, was developed, standardized, and assessed for reproducibility.
      After a review of the literature concerning attempts and approaches with various
      species, a technique involving an approach through the external auditory canal
      was chosen and modified. Using a stereomicroscope, a cutaneous incision in the
      intertragic notch was made and extended medially along the ventral aspect of the
      external auditory canal to the depth of the external auditory meatus. The
      tympanic membrane was ruptured and the malleus removed with splinter forceps,
      allowing visualization of the cochlea. The lateral wall of the cochlea was
      penetrated with a 0.024-in. wire gauge drill bit and endolymph was suctioned from
      the cochlea. A 5-mm piece of 3-O silk suture, inserted into the cochlear opening,
      maintained patency. Appraisal of the reliability and standardization of the
      procedure was performed utilizing startleometry. Histology assessed completeness
      of the procedure and any evidence of cochlear infection.

PMID- 8292572
TI  - Liver transplantation in pigs: a model for studying reperfusion injury.
AB  - A model of orthotopic liver transplantation in pigs was developed to investigate
      reperfusion injury of the liver. To have direct access to the liver for organ
      monitoring a relaparotomy was performed 6 h after revascularization. The details
      of modification in anesthesia and surgical technique are given. Salient features
      of the technique include (1) the use of an extremely short cuff of the donor
      suprahepatic caval vein, (2) the use of a central venous catheter fixed in a
      hepatic vein, and (3) the use of an aortic graft for standardized arterial
      reconstruction. Twenty-nine transplantations were performed. The total anesthetic
      time was 13.28 +/- 1.45 h and the operative time was 10.06 +/- 0.77 h. The
      animals withstood this long procedure remarkably well.

PMID- 8292573
TI  - A conscious baboon model for evaluation of hemodynamics in altered gravity.
AB  - A model was developed for evaluation of cardiovascular parameters in conscious
      baboons exposed to altered gravitational environments. Baboons were trained to
      sit quietly in a confinement chair of unique design which allowed a range of
      normal physical activity. They were then instrumented with high-fidelity blood
      pressure transducers in the aorta and left ventricle, electromagnetic flow probes
      encircling the proximal ascending aorta, left and right atrial fluid catheters,
      left ventricular sonomicrometer crystals in a 3-axis configuration, and a
      hydraulic occluder cuff encircling the inferior vena cava. Catheters and
      transducer wires were exteriorized at the midscapular region of the back.
      Viability of percutaneous exit sites was enhanced by use of velour cuffs on the
      transducer wires, providing a scaffold for wound healing. Pressure transducers
      and flow probes were calibrated and balanced during postoperative cardiac
      catheterization procedures. This instrumentation allowed measurement of beat-to
      beat stroke volume and cardiac output not reliant on thermodilution techniques.
      Postoperative longevity was from 1 to 10 months. Instrumentation failure included
      endocardial trapping of ventricular pressure transducers, corrosion of
      ventricular sonomicrometer crystals, and catheter tip thrombosis. Acquisition of
      high quality data was possible with this model in several different environments
      of altered gravitational stress, allowing characterization of aortic flow and
      ventricular performance.

PMID- 8292574
TI  - Implanted right atrial catheters for continuous infusion of solutions into dogs.
AB  - Silastic catheters were fabricated and aseptically implanted through the skin
      into the jugular vein of 64 dogs with the intravascular tip located in the right
      atrium. Solutions were infused through the catheter at 2 to 2.5 mL/h by a
      portable pump worn by the dog. Following 9.2 Gy total body irradiation (TBI) and
      allogeneic bone marrow transplantation (BMT), succinyl acetone, an experimental
      chemotherapeutic agent, was infused into 34 dogs. Hematopoietic growth factors
      were infused into an additional 30 dogs, two of which had 9.2 Gy TBI and an
      autologous BMT, and four of which had 4.0 Gy TBI and no BMT. All dogs received
      continuous oral and parenteral antibiotics while the catheters were in place. All
      catheters functioned well until electively removed (n = 28) or until the dogs
      died or were euthanized (n = 36) at 12 to 68 days after implantation. Mean length
      of catheter function was 30.3 +/- 1.5 (SEM) days. No catheters were dislodged and
      there was no evidence of catheter-related blood loss or sepsis. Semiquantitative
      cultures of 5 catheters were negative, but Staphylococcus epidermidis was
      isolated from 3 of 7 catheters cultured in broth. Six dogs had thrombosis
      adjacent to the intravascular catheter tip. The catheters were well tolerated and
      facilitated successful long-term infusion of solutions into dogs.

PMID- 8292575
TI  - A biomechanical study of bicycle helmets' effectiveness in childhood.
AB  - The authors present the results of a series of impact tests on pedal cycle
      helmets. 10 helmets were tested using a drop test under three different test
      conditions: Left frontal/temporal from 1 m, right frontal/temporal from 1.5 m and
      left occipital from 1 m. Impact force and the acceleration of the headform's
      centre of gravity in three axes were measured. As a result of the authors' field
      research on pedal cycle helmets in Australia the 1.5 m drop height was considered
      to be more representative of a "real" accident than the less severe 1 m height
      fall. The range of resultant maximal accelerations, 1 m drop height, was 81 g to
      193 g; 1.5 m drop height 122 g to 209 g. In comparison a fall without helmet from
      0.5 m produced a maximal resultant acceleration of 282 g. Head injury criteria
      values were for 1 m drops between 201 and 630; from 1.5 m 547 to 1078; and
      without helmet from 0.5 m 906. The individual helmets are compared on these
      figures and their merits discussed.

PMID- 8292576
TI  - Aortopexy for tracheomalacia in oesophageal anomalies.
AB  - Forty-eight patients with repaired congenital oesophageal anomaly underwent
      aortopexy for significant tracheomalacia between 1980 and 1990. Indications for
      aortopexy included recurrent apnoea/cyanosis in 31, near fatal episodes in 16,
      recurrent respiratory distress and infection in 20 and worsening stridor in 15.
      Gastro-oesophageal reflux was noted in 30 patients, recurrent fistula in 6 and
      oesophageal stricture in 14. Aortopexy cured near fatal episodes in all patients
      and resulted in improvement of airway obstruction in 95%. The procedure failed in
      2 patients due to unrecognised bronchomalacia and phrenic nerve palsy
      respectively. Aortopexy is the primary procedure of choice for significant
      tracheomalacia when associated with near fatal episodes and significant airway
      obstruction.

PMID- 8292577
TI  - Congenital duodenal obstruction: an approach to diagnosis.
AB  - 53 neonates with congenital duodenal obstruction presented to Our Lady's Hospital
      for Sick Children over a consecutive 4-year period. Of these 53, 27 presented
      with intrinsic obstruction, and 26 with extrinsic obstruction. Diagnostic methods
      and features resulting in surgically proven diagnoses are discussed.

PMID- 8292578
TI  - Initial evaluation of children sustaining blunt abdominal trauma: ultrasonography
      vs. diagnostic peritoneal lavage.
AB  - A prospective clinical study was performed to compare ultrasonography (US) with a
      modality having 96-99% accuracy like diagnostic peritoneal lavage (DPL) to find
      the accuracy of US in the initial evaluation of children sustaining blunt
      abdominal trauma (BAT). Sixty-eight children with BAT were initially evaluated by
      US, then DPL. All patients with pathologic US findings underwent computerized
      tomographic examination before DPL to confirm the pathologies. Through US
      examination free intraperitoneal fluid (FIF) was present in eleven, absent in 57
      patients. DPL was positive in ten, negative in 58 patients. Sensitivity,
      specificity, negative predictive value, positive predictive value and efficiency
      of US were 100, 98.3, 100, 91 and 98.5 respectively. US detected intraperitoneal
      solid organ injuries in eleven patients, but DPL was positive in only ten of
      these patients. While US detected renal injuries in six patients and intrapleural
      fluid in two patients, DPL was positive in only two of these patients as a result
      of concomitant intraperitoneal solid organ injuries with FIF. The present study
      has shown that US can detect FIF with a high rate of accuracy comparable to DPL
      in children. In addition, US has advantages over DPL in the detection of
      intraperitoneal organ injuries with or without concomitant FIF, retroperitoneal
      injuries and intrathoracic injuries. Thus US is thought to be superior to DPL and
      recommended as a routine first choice screening tool in the initial evaluation of
      children sustaining BAT.

PMID- 8292579
TI  - Double pigtail ureteral stent in pediatric urology.
AB  - We used a double pigtail ureteral stent in 16 children (aged 15 days to 13
      years). Indications included: pyeloplasty (12 cases with 2 anastomotic leakages
      and 1 acute post-operative renal retention), renal trauma (1 case), difficult
      ureterocystoneostomy (1 case), urinary ascites (1 case), and abdominal tumor
      compression (1 case). This drainage procedure provides a useful alternative to an
      external tube diversion (standard ureteral stent or nephrostomy). In pediatric
      urology, the double stent offers the advantages of exceptional patient tolerance,
      drainage security and efficiency, and short hospital stay. In our experience,
      stents were removed on an out-patient basis under general anesthesia but non
      endoscopic removal will be possible when smaller magnetic retrievers become
      available in the urologic armamentarium.

PMID- 8292580
TI  - A long-term follow-up study of children with supracondylar fractures of the
      humerus.
AB  - A retrospective study to assess the long-term results of the treatment of
      supracondylar fractures of the humerus was undertaken to provide guidance on the
      management of these troublesome injuries. In our experience as long as there was
      less than 25% displacement on an anteroposterior (A/P) or lateral x-ray, and less
      than 10 degrees angulation on an A/P or lateral x-ray, it is not essential to
      achieve an anatomical reduction, and good elbow function could be expected.
      Although children do not appear to correct for valgus or varus deformity there
      was no functional deficit from this deformity in this series. It was found that
      major displacements were more likely to have a worse result than undisplaced or
      minimally displaced fractures. These results would support a conservative
      approach to the management of these fractures--closed reduction followed by three
      weeks in a collar and cuff. If the position proved unstable, closed reduction was
      re-attempted or internal fixation performed. Conservative treatment was safe and
      effective, and the results comparable with other series that advocate internal
      fixation.

PMID- 8292581
TI  - A technique of doubling the cremasteric muscle in large inguinal hernia repair in
      infants and children--a late follow-up.
AB  - Between 1969 and 1988, 259 large inguinal hernias in 241 male infants and
      children were repaired, using a technique of doubling the cremasteric muscle,
      representing 1.12% of all inguinal hernia repairs in this time period. In a late
      follow-up, 4 to 20 years postoperatively, 195 patients (81%) with 204 hernia
      repairs by doubling of the cremasteric muscle were re-evaluated. Postoperative
      complications occurred in 3 patients, one recurrence of the hernia, one
      testicular atrophy after an incarcerated hernia and one trapped testicle. The
      technique of doubling the cremasteric muscle in large inguinal hernia repair in
      male infants and children represents an alternative and safe operative procedure
      without further complications.

PMID- 8292582
TI  - Microgastria--case report and a review of the literature.
AB  - The case of a female baby with microgastria, duodenal atresia, asplenia,
      hydrocephalus and many other anomalies is reported. She underwent repair of the
      duodenal atresia at the age of 3 days and died of sepsis at the age of 5 months.
      Twenty-nine cases of microgastria found reported in the literature are reviewed.

PMID- 8292583
TI  - Congenital diaphragmatic hernia and intrathoracic intestinal volvulus.
AB  - The main symptom of the congenital diaphragmatic hernia (CDH) is the respiratory
      distress due to the pulmonary hypoplasia and the persistence of foetal pulmonary
      circulation. Sometimes the CDH appears outside of the neonatal period with
      respiratory symptoms, abdominal pain and seldom with intestinal obstruction. A
      case of CDH presenting with intrathoracic volvulus is reported. This case shows
      that tendency of delayed repair until the newborn has been recovered, require
      more attention because the good condition of the patient can be changed not only
      by the pulmonary hypoplasia and the persistence of the foetal pulmonary
      circulation but also by the symptoms of the intrathoracic gut complications.

PMID- 8292584
TI  - Delayed presentation of intestinal atresia and intussusception--a case report and
      literature review.
AB  - Neonatal intussusception is a rare phenomenon. We report a case where intestinal
      obstruction became evident after eight days in an infant of 32 weeks gestational
      age and 0.94 kg birth weight. Laparotomy revealed a type 2 ileal atresia, present
      as a result of ischaemic injury secondary to intra-uterine intussusception.
      Resection of the intussuscepted segment was carried out with primary anastomotic
      repair leading to a good outcome. A period of eight days passed before clinically
      evident abdominal distension was noted. We address reasons why this may have
      occurred.

PMID- 8292585
TI  - Familial intussusception: report of a case with recurrence in the youngest
      sibling and review of the literature.
AB  - The etiology of idiopathic intussusception is unknown. Occurrence of
      intussusception in more than one patient in a same family is rare. A familial
      predisposition is suspected. We present a family in which the two children
      suffered from intussusception with recurrence in the youngest sibling and review
      the literature.

PMID- 8292586
TI  - Leiomyosarcoma of the cecum in pediatric age: a case report and review of Italian
      reports.
AB  - The authors report a case of leiomyosarcoma of the cecum and review all the
      Italian reports of mesenchymal neoplasms registered in the RMS-Italy register.
      They emphasize the extreme rarity of intestinal leiomyosarcoma, especially with
      colon involvement: their case appears to be the only one registered in Italy in
      the last 12 years.

PMID- 8292587
TI  - Pre- and postoperative urodynamic and anorectal manometric findings in children
      operated upon for a primary tethered cord.
AB  - The aim of the study was to assess the sensitivity of both urodynamics and
      anorectal manometry in detecting neurological signs in children with a primary
      tethered cord. Between 1989 and 1991, 9 children were operated upon for
      untethering of primary tethered cord in Lausanne. Both manometric studies were
      performed by the same team preoperatively and 6 months after surgery. Gaeltec
      catheters with micro-tip transducers were used with a standardized method.
      Preoperative manometric findings were pathological in 4 children without clinical
      signs of bladder dysfunction and in 3 without clinical fecal disorders.
      Postoperatively, bladder dysfunction regressed in one child and fecal disorders
      in another. Manometric findings remained nevertheless pathological. The authors
      held both urodynamics and anorectal manometry as mandatory for preoperative
      evaluation as well as for the postoperative monitoring of children with primary
      tethered cord.

PMID- 8292588
TI  - Blue rubber-bleb-nevus syndrome with predominant urinary bladder hemangiomatosis.
AB  - In a 2-year-old girl a blue rubber-bleb-nevus syndrome is described. Apart from
      cutaneous hemangiomas, pronounced hemangiomas of the urinary bladder were
      diagnosed and treated by laser surgery. The features of the disorder are
      discussed as a special clinical condition within the framework of this syndrome.

PMID- 8292589
TI  - Intracellular signaling activity of synthetic (14R)-, (14S)-, and (14RS)-14
      hydroxy-4,14-retro-retinol.
AB  - 14-Hydroxy-4,14-retro-retinol (14-HRR), first isolated from cultures of
      lymphoblastoid 5/2 and HeLa cells and characterized by NMR, UV, and CD, is a
      metabolite of retinol which promotes growth of B lymphocytes in culture and
      activation of T lymphocytes by antigen receptor-mediated signals. It is also
      produced by various tested cell lines: fibroblasts, leukemia, and Drosophila
      cells. 14-HRR is the first bioactive retro-retinoid to be discovered and, after
      retinal and retinoic acid, is the third intracellular messenger molecule derived
      from retinol. Physical properties and intracellular signaling activities of
      synthetic (14R)-HRR, (14S)-HRR, and racemic 14-HRR are described. CD spectra
      indicate that natural 14-HRR isolated previously was a mixture of enantiomers. B
      cell survival and T-cell activation assays performed in the optimal range of (7
      1.6) x 10(-7) M surprisingly showed that all 14-HRR compounds exhibit similar
      activity, with the 14R enantiomer exhibiting slightly higher activity in
      comparison to the 14S enantiomer. However, because of the semiquantitative nature
      of the assays, the conclusion as to which enantiomer is more active and which is
      the true ligand for the target receptor must await characterization of this
      protein.

PMID- 8292590
TI  - Aspartate receptors of Escherichia coli and Salmonella typhimurium bind ligand
      with negative and half-of-the-sites cooperativity.
AB  - The aspartate receptors of Escherichia coli and Salmonella typhimurium which
      mediate chemotactic responsiveness to aspartate have 79% amino acid sequence
      identity but exhibited apparently quite different aspartate binding plots. The
      Scatchard plot of the Salmonella receptor was concave upward whereas the E. coli
      receptor gave a straight line. Because the two binding sites in the Salmonella
      receptor lacking aspartate have a 2-fold crystallographic symmetry axis and do
      not overlap, the observation of more than one class of binding sites must be due
      to a ligand-induced conformational change giving negative cooperativity. The
      closely related E. coli receptor was found to bind with only one class of sites
      but with a stoichiometry of one aspartate per dimer. The E. coli receptor thus
      binds with half-of-sites reactivity, an extreme form of negative cooperativity in
      which the second ligand is not observed to bind at all. Comparison of the X-ray
      crystal structure of the ligand binding domain with and without bound aspartate
      revealed ligand-induced conformational changes that explain the two examples of
      negative cooperativity.

PMID- 8292591
TI  - The role of lysine 166 in the mechanism of mandelate racemase from Pseudomonas
      putida: mechanistic and crystallographic evidence for stereospecific alkylation
      by (R)-alpha-phenylglycidate.
AB  - The mechanism of irreversible inactivation of mandelate racemase (MR) from
      Pseudomonas putida by alpha-phenylglycidate (alpha PGA) has been investigated
      stereochemically and crystallographically. The (R) and (S) enantiomers of alpha
      PGA were synthesized in high enantiomeric excess (81% ee and 83% ee,
      respectively) using Sharpless epoxidation chemistry. (R)-alpha PGA was determined
      to be a stereospecific and stoichiometric irreversible inactivator of MR. (S)
      alpha PGA does not inactivate MR and appears to bind noncovalently to the active
      site of MR with less affinity than that of (R)-alpha PGA. The X-ray crystal
      structure (2.0-A resolution) of MR inactivated by (R)-alpha PGA revealed the
      presence of a covalent adduct formed by nucleophilic attack of the epsilon-amino
      group of Lys 166 on the distal carbon on the epoxide ring of (R)-alpha PGA. The
      proximity of the alpha-proton of (S)-mandelate to Lys 166 [configurationally
      equivalent to (R)-alpha PGA] was corroborated by the crystal structure (2.1-A
      resolution) of MR complexed with the substrate analog/competitive inhibitor, (S)
      atrolactate [(S)-alpha-methylmandelate]. These results support the proposal that
      Lys 166 is the polyvalent acid/base responsible for proton transfers on the (S)
      face of mandelate. In addition, the high-resolution structures also provide
      insight into the probable interactions of mandelate with the essential Mg2+ and
      functional groups in the active site.

PMID- 8292592
TI  - NMR analysis reveals a positively charged hydrophobic domain as a common motif to
      bound acetylcholine and d-tubocurarine.
AB  - A complete 1H assignment of d-tubocurarine was carried out using 1D and 2D NMR
      techniques. Geometries of free acetylcholine (ACh) and d-tubocurarine were
      compared with those of the ligands bound to a recombinant cholinergic binding
      site (T alpha 184-200 expressed as a fusion protein in Escherichia coli). The
      conformations of the free ligands were determined by NOESY experiments while
      those of the bound molecules were obtained by transferred NOESY. The complete
      relaxation matrix was solved yielding distance constraints which were further
      refined by a sigma back-calculation. ACh bound to recombinant T alpha 184-200
      closely resembled the conformation previously reported for ACh bound to the
      intact receptor. d-Tubocurarine in the bound state undergoes extensive induced
      conformational rearrangements generating a "cup"-shaped structure. A unique
      positively charged hydrophobic domain is identified as characteristic of both
      bound cholinergic ligands.

PMID- 8292593
TI  - Formation of multiple complexes between actinomycin D and a DNA hairpin:
      structural characterization by multinuclear NMR.
AB  - The solution conformations of a DNA oligomer and its complexes with the
      anticancer drug actinomycin D (ActD) were characterized using homo- and
      heteronuclear NMR techniques. Previous high-resolution NMR investigations of ActD
      DNA complexes employed symmetric double-stranded DNA oligomers, yielding two
      identical symmetry-related complexes. In order to understand the important
      effects that neighboring base pairs and/or unusual nucleic acid structures may
      have on ActD binding specificity and orientation, we chose to study the
      oligonucleotide d(TCGCGTTTTCGCGA), which adopts a hairpin structure in solution.
      NOE cross-peak intensities were used to generate distance constraints for
      molecular dynamics simulations and structure determinations of the free
      oligonucleotide and for both complexes. A total of 86 intermolecular NOEs were
      identified for each complex, 27 of which involve exchangeable protons. These
      intermolecular NOEs along with changes in the phosphorus chemical shifts were
      used to determine the drug binding site on the DNA. As expected, ActD
      intercalated exclusively at the single d(GC) step in the DNA hairpin.
      Interestingly, although the two complexes, which differ by the orientation with
      which the asymmetric drug chromophore intercalates the DNA, were not formed in
      equal concentrations, their conformations are very similar. The RMS difference of
      the DNA hairpin in the two complexes is only 1.10 A. The structures of the minor
      groove binding pentapeptide rings are not affected by any of the changes in the
      normal double-helical structure imposed by the hairpin loop. The total pairwise
      RMS difference over all atoms for the four peptides (two per complex) in the
      calculated structures is 0.72 A. Conversely, the structure of the hairpin loop is
      not appreciably changed upon binding--the RMS difference between the free DNA
      loop region and the loop region in the two complexes is 1.68 A and only 0.43 A
      between the two complexes. Our data also support a possible conformation of the
      d(T)4 loop that does not possess a thymine-thymine "wobble" base pair.

PMID- 8292594
TI  - Hairpin folding of subunit c of F1Fo ATP synthase: 1H distance measurements to
      nitroxide-derivatized aspartyl-61.
AB  - Subunit c from the F1Fo ATP synthase of Escherichia coli folds in a hairpinlike
      structure of two alpha-helices in a solution of chloroform-methanol-H2O, and thus
      resembles the structure predicted for the folded protein in the membrane. The
      relevance of the structure in solution to the native structure was demonstrated.
      Asp61 in the second helical arm was shown to retain its unique reactivity with
      dicyclohexylcarbodiimide (DCCD) in chloroform-methanol-H2O solution. Further, the
      protein purified from the Ile28-->Thr DCCD-resistant mutant proved to be less
      reactive with DCCD in solution. This suggested that the protein folded with Ile28
      of the first helical arm close to Asp61 in the second helical arm. Subunit c in
      wild-type E. coli membranes was specifically labeled with a nitroxide analog of
      DCCD (NCCD), and the derivative protein was purified. DQF COSY spectra were
      recorded, and the distances between the paramagnetic nitroxide and resolved
      protons in the spectra were calculated based upon paramagnetic broadening of the
      1H resonances. The paramagnetic contribution to T2 relaxation in the NCCD-labeled
      sample was calculated by an iterative computer-fitting method, where a control
      spectrum of a phenylhydrazine-reduced sample was broadened until the line shape
      of one-dimensional slices through each COSY cross-peak maximally mimicked the
      line shape of the paramagnetic sample. The distances calculated from paramagnetic
      broadening indicate that Ala24 and Ala25 in helix-1 lie close (ca. 12 A) to the
      derivatized Asp61 in helix-2. A model for the interaction of helices in the NCCD
      modified protein was generated by restrained molecular mechanics and molecular
      dynamics using 25 distances of < 10-20 A derived from paramagnetic broadening in
      combination with 15 long-range nuclear Overhauser enhancement (NOE) restraints (2
      5 A) for distances between helices and the 89 intrahelical NOEs that defined
      helical structure in the DCCD-modified protein.

PMID- 8292595
TI  - Characterization of folding intermediates using prolyl isomerase.
AB  - Structure-reactivity relationships of human peptidyl prolyl cis-trans isomerase
      (PPI) toward the two slow folding reactions of yeast iso-2 cytochrome c have been
      used to characterize the structure of folding intermediates in the vicinity of
      critical prolines. We propose that the relative catalytic efficiency of PPI for
      the protein substrate relative to a peptide substrate, (kcat/Km)rel, is a measure
      of structure in folding intermediates. The structural stability of slow-folding
      intermediates as detected by changes in (kcat/Km)rel was investigated using two
      structural perturbants: guanidine hydrochloride and site-directed mutagenesis.
      Neither of the two slow folding reactions for wild-type cytochrome c is catalyzed
      at low denaturant concentrations. However, both phases are catalyzed at moderate
      concentrations of guanidine hydrochloride. A mutation in cytochrome c enhances
      catalysis of the fluorescence-detected slow folding phase. For protein substrates
      destabilized by denaturants or mutation, we suggest that increases in
      (kcat/Km)rel result from a loosening of the substrate structure, providing better
      access of peptidyl prolyl isomerase to critical proline(s).

PMID- 8292596
TI  - Conformation of ATP and ADP bound to N10-formyltetrahydrofolate synthetase
      determined by TRNOE NMR spectroscopy.
AB  - ATP and ADP bind to N10-CHO-H4folate synthetase from Clostridium cylindrosporum
      at four identical sites. Although both ADP and ATP bind to the enzyme with
      essentially the same Ka values as the Mg2+.nucleotide complexes, only the
      Mg2+.nucleotides are kinetically active. Using transferred nuclear Overhauser
      effect (TRNOE) NMR spectroscopy, we have measured the time-dependent NOE buildup
      rates of selected protons in ADP and ATP bound to N10-CHO-H4folate synthetase
      after preirradiating protons H1', H2', H3', and H4'. The results were used to
      calculate interproton distances. In order to define the conformations of ADP and
      ATP bound to the enzyme, we used the TRNOE distance constraints in a distance
      geometry algorithm. The results of the distance geometry calculations suggest
      that, within experimental error, the conformations of both ADP and ATP (with or
      without Mg2+) have an average glycosidic torsion angle X (O4'-C1'-N9-C8) of 100
      degrees +/- 20 degrees and a sugar pucker angle psi' (C5'-C4'-C3'-O3') of 85
      degrees +/- 5 degrees. These values are consistent with a nucleotide structure
      generated by computer modeling after energy minimization, which has X = 90
      degrees +/- 6 degrees and psi' = 81 degrees, indicating a high-anti and C3'-endo
      conformation.

PMID- 8292597
TI  - Resonance Raman and optical spectroscopic monitoring of heme a redox states in
      cytochrome c oxidase during potentiometric titrations.
AB  - Resonance Raman spectroscopy is used to monitor the redox state of heme a and
      heme a3 centers in cyanide-inhibited and native cytochrome oxidase during
      potentiometric titrations. Specific vibrational modes are resolved for each
      reduced heme with 441.6-nm excitation while oxidized species show vanishingly
      small Raman intensities. The voltage dependencies of the Raman intensities of
      reduced heme a and reduced heme a3 modes are quantitatively measured and used to
      extract heme a and a3 midpoint potentials. In the cyanide-bound enzyme, in which
      heme a3 remains in the oxidized state, the Raman data indicate that heme a
      centers exhibit complex Nernstian behavior with two Em values near 350 and 260
      mV. In the native enzyme, this resonance Raman-potentiometric method reveals
      significantly different redox behavior for the two hemes. Heme a centers are
      described by two effective Em values near 350 and 220 mV, while heme a3 centers
      have lower Em values near 260 and 200 mV. Singular value decomposition analysis
      of optical spectral changes supports the Raman data. These results are in
      contrast to models of cytochrome oxidase redox behavior in which heme a and heme
      a3 are thought to have essentially identical midpoint potentials.

PMID- 8292598
TI  - A conformational change associated with the phototransformation of Pisum
      phytochrome A as probed by fluorescence quenching.
AB  - Dynamic quenching of the two lifetime component tryptophan fluorescence of Pisum
      phytochrome has revealed differential accessibility of certain residues. Both
      acrylamide and Tl+ ions showed preferential exposure of some tryptophans in Pfr
      phytochrome. Greater kq's for Pfr are, however, in contrast with values for Avena
      phytochrome in which Pr-->Pfr conversion impedes Tl+ access. The Pr short
      lifetime component was more accessible to Cs+; however, the long component
      accessibility was approximately 2-fold higher in Pfr. 2-Hydroxy-5-nitrobenzyl
      bromide (HNB-Br) modification of native Pisum phytochrome was used to reduce the
      total number of fluorescent tryptophans. The absence of the fluorescence
      contributions of the three residues which reacted with HNB-Br in both
      photoisomers increased the Tl+ Ksv's for Pr and Pfr. The two additional HNB-Br
      modifications specific for Pfr resulted in a reversal of the Stern-Volmer plots
      relative to the unmodified protein. The regions around four of the 10 tryptophans
      may represent conformationally photoresponsive areas in Pisum phytochrome A.
      Furthermore, topographic changes associated with the phytochrome
      phototransformation are not confined to the 58-kDa chromphore domain, and they
      involve most if not all of the region from Trp-365 to Trp-787. We also provide
      evidence that the protein conformation in this region is not completely conserved
      between Pisum and Avena phytochromes.

PMID- 8292599
TI  - Oxidation-reduction potentials of the methane monooxygenase hydroxylase component
      from Methylosinus trichosporium OB3b.
AB  - Methane monooxygenase (MMO) isolated from Methylosinus trichosporium OB3b
      consists of hydroxylase (MMOH), reductase (MMOR), and "B" (MMOB) protein
      components. MMOH contains two oxygen-bridged dinuclear iron clusters that are the
      sites of O2 activation and hydrocarbon oxidation. Each cluster can be stabilized
      in diferric [Fe(III).Fc(III)], mixed-valence [Fe(II).Fe(III)], and diferrous
      [Fe(II).Fe(II)] redox states. We have correlated the EPR spin quantitation of the
      S = 1/2 mixed-valence state with the system electrode potential to determine both
      formal redox potential values for MMOH at 4 degrees C: E1 degrees' = +76 +/- 15
      mV and E2 degrees' = +21 +/- 15 mV (Em = +48 mV, 61% maximum mixed-valence
      state). Complementary Mossbauer studies of 57Fe-enriched MMOH allowed all three
      redox states to be quantitated simultaneously in individual samples and revealed
      that the distribution of redox states was in accord with the measured potential
      values. EPR spectra of partially reduced MMOH showed that the apparent midpoint
      potential values of MMOH-MMOR, MMOH-MMOR-MMOB, and MMOH-MMOR-MMOB-substrate
      complexes were slightly more positive than that of MMOH alone. In contrast, the
      MMOH-MMOB complex appeared to have a substantially more negative redox potential.
      The formal redox potential values of the latter complex were determined to be E1
      degrees' = -52 +/- 15 mV and E2 degrees' = -115 +/- 15 mV, respectively, at 4
      degrees C (Em = -84 mV, 65% maximum mixed-valence state). This negative 132-mV
      shift in the midpoint potential of MMOH coupled to MMOB binding suggests that
      MMOB binds approximately 10(4) more strongly to the diferric state of MMOH than
      to the diferrous state. Since the potential shift is strongly negative, and since
      a nearly constant separation between the two formal potential values of MMOH is
      maintained when MMOB binds, the role of the MMOB-MMOH complex must not be to
      thermodynamically stabilize the formation of the diferrous cluster which is the
      form that reacts with O2 during catalysis. However, MMOB binding may provide
      kinetic stabilization of the diferrous state and/or modulation of the interaction
      of MMOH with O2 and hydrocarbon substrates. Such roles may be effected through
      cyclic association and dissociation of the MMOB-MMOH complex as MMOH oscillates
      between redox states during catalysis, thereby dynamically altering the affinity
      of this complex.

PMID- 8292600
TI  - Requirement of histidine 217 for ubiquinone reductase activity (Qi site) in the
      cytochrome bc1 complex.
AB  - Folding models suggest that the highly conserved histidine 217 of the cytochrome
      b subunit from the cytochrome bc1 complex is close to the quinone reductase (Qi)
      site. This histidine (bH217) in the cytochrome b polypeptide of the
      photosynthetic bacterium Rhodobacter capsulatus has been replaced with three
      other residues, aspartate (D), arginine (R), and leucine (L). bH217D and bH217R
      are able to grow photoheterotrophically and contain active cytochrome bc1
      complexes (60% of wild-type activity), whereas the bH217L mutant is
      photosynthetically incompetent and contains a cytochrome bc1 complex that has
      only 10% of the wild-type activity. Single-turnover flash-activated electron
      transfer experiments show that cytochrome bH is reduced via the Qo site with near
      native rates in the mutant strains but that electron transfer between cytochrome
      bH and quinone bound at the Qi site is greatly slowed. These results are
      consistent with redox midpoint potential (Em) measurements of the cytochrome b
      subunit hemes and the Qi site quinone. The Em values of cyt bL and bH are
      approximately the same in the mutants and wild type, although the mutant strains
      have a larger relative concentration of what may be the high-potential form of
      cytochrome bH, called cytochrome b150. However, the redox properties of the
      semiquinone at the Qi site are altered significantly. The Qi site semiquinone
      stability constant of bH217R is 10 times higher than in the wild type, while in
      the other two strains (bH217D and bH217L) the stability constant is much lower
      than in the wild type. Thus H217 appears to have major effects on the redox
      properties of the quinone bound at the Qi site. These data are incorporated into
      a suggestion that H217 forms part of the binding pocket of the Qi site in a
      manner reminiscent of the interaction between quinone bound at the Qb site and
      H190 of the L subunit of the bacterial photosynthetic reaction center.

PMID- 8292601
TI  - Pathway of proton transfer in bacterial reaction centers: role of aspartate-L213
      in proton transfers associated with reduction of quinoneto dihydroquinone.
AB  - The role of Asp-L213 in proton transfer to reduced quinone QB in the reaction
      center (RC) from Rhodobacter sphaeroides was studied by site-directed replacement
      of Asp with residues having different proton donor properties. Reaction centers
      (RCs) with Asn, Leu, Thr, and Ser at L213 had greatly reduced (approximately 6000
      fold) proton-coupled electron transfer [kAB(2)] and proton uptake rates
      associated with the second electron reduction of QB (QA- QB- + 2H(+)-->QAQBH2)
      compared to native RCs. RCs containing Glu at L213 showed faster (approximately
      90-fold) electron and proton transfer rates than the other mutant RCs but were
      still reduced (approximately 70-fold) compared with native RCs. These results
      show that kAB(2) is larger when a carboxylic acid occupies the L213 site,
      consistent with the proposal that Asp-L213 is a component of a proton transfer
      chain. The reduced kAB(2) observed with Glu versus Asp at L213 suggests that Asp
      at L213 is important for proton transfer for some other reason in addition to its
      proton transfer capabilities. Glu-L213 is estimated to have a higher apparent pKa
      (pKa > or = 7) than Asp-L213 (pKa < or = 4), as indicated by the slower rate of
      charge recombination (D+QAQB(-)-->DQAQB) in the mutant RCs. The importance of the
      pKa and charge of the residue at L213 for proton transfer are discussed. Based on
      these studies, a model for proton transfer is proposed in which Asp-L213
      contributes to proton transfer in native RCs in two ways: (1) it is a component
      of a proton transfer chain connecting the buried QB molecule with the solvent
      and/or (2) it provides a negative charge that stabilizes a proton on or near QB.

PMID- 8292602
TI  - Comparison of calcium-dependent conformational changes in the N-terminal SH2
      domains of p85 and GAP defines distinct properties for SH2 domains.
AB  - Src-homology region 2 (SH2) domains are stretches of about 100 amino acids which
      are found to be structurally conserved in a number of signaling molecules. These
      regions have been shown to bind with high affinity to phosphotyrosine residues
      within activated receptor tyrosine kinases. Here we report the bacterial
      expression and purification of individual N-terminal SH2 (NSH2) domains of
      phosphatidylinositol 3-kinase (PI-3K) binding subunit (p85) and Ras GTPase
      activating protein (GAP) in amounts suitable for structure-function studies. The
      p85NSH2 domain stains dark purple and absorbs around 620-640 nm with Stains-all,
      a dye known to bind to calcium binding proteins. This effect was not observed for
      the GAPNSH2 domain. Circular dichroism analysis of the N-terminal SH2 domain of
      these proteins shows that p85NSH2, but not GAPNSH2, undergoes a significant dose
      dependent change in conformation in the presence of increasing calcium
      concentrations. Moreover, the conformational change of p85NSH2 induced by calcium
      could be replicated by addition of a phosphorylated hexapeptide (DYpMDMK)
      representing the alpha-PDGFR binding site for p85. Limited proteolysis studies
      showed a significant calcium-dependent increase in protection of p85NSH2 but not
      GAPNSH2 from degradation by subtilisin. Our results further indicate that
      holmium, a trivalent lanthanide ion, which has been previously shown to
      substitute for calcium, could also protect the p85NSH2 domain from proteolysis
      even at 10-fold lower concentrations. In vitro binding studies using purified
      preparations of activated alpha-PDGFR show that calcium did not affect the
      binding of GAPNSH2 domains to activated alpha-PDGFR.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8292603
TI  - Reconstitution of purified GABAA receptors: ligand binding and chloride
      transporting properties.
AB  - GABAA receptors have been solubilized from bovine brain membranes and, following
      purification by benzodiazepine affinity chromatography, have been reconstituted
      into phospholipid vesicles. Reconstituted vesicles were about 120 nm in diameter,
      and, on average, each vesicle contained fewer than one GABAA receptor which was
      reconstituted in an outside-out orientation. These preparations have been used in
      parallel studies of radiolabeled ligand binding and chloride flux, the latter
      being measured by following the fluorescence changes of a chloride-sensitive
      probe which was trapped within the vesicles at the time of reconstitution. The
      benzodiazepine [3H]flunitrazepam binds to an apparently homogeneous population of
      sites in these preparations (Kd of 5 nM) whereas the GABA analogue [3H]muscimol
      binds to both high- and low-affinity sites (KdS of 10 nM and 0.27 microM).
      Muscimol stimulated chloride flux with an EC50 of 0.2 microM and, at similar
      concentrations (EC50 = 0.16 microM), potentiated [3H]flunitrazepam binding,
      suggesting that occupancy of the low-affinity sites may be important for these
      effects. Diazepam shifted the dose-response curve for muscimol-stimulated flux to
      about 4-fold lower concentrations without affecting the maximum response.
      Diazepam did not, however, alter the equilibrium binding of [3H]muscimol. The
      purified receptor showed densensitization since flux responses were abolished by
      prior exposure to muscimol. The competitive antagonist bicuculline and the
      channel blocker picrotoxin completely inhibited ion flux mediated by 3 microM
      muscimol with EC50 values of 5.3 and 2.5 microM, respectively. These results are
      discussed in terms of possible mechanisms for activation, inhibition, and
      modulation of GABAA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292604
TI  - Use of single-turnover kinetics to study bulky adduct bypass by T7 DNA
      polymerase.
AB  - The mechanism by which T7 DNA polymerase (exo-) bypasses N-2-acetylaminofluorene
      (AAF) and N-2-aminofluorene (AF) adducts was studied by single-turnover kinetics.
      These adducts are known to be mutagenic in several cell types, and their bypass
      was studied in the framework of understanding how they promote mutations.
      Synthetic primer/templates were made from a template sequence containing a single
      guanine, to which the adducts were covalently attached, and one of three primers
      whose 3' ends were various distances from the adduct in the annealed substrates.
      Upon approaching the site of either adduct, the polymerase was found to add
      nucleotides as rapidly as to unmodified primer/templates, until just opposite the
      lesion. The incorporation rate of dCTP (at 100 microM) opposite AF-dG or AAF-dG
      was approximately 5 x 10(4)- and 4 x 10(6)-fold slower, respectively, than
      incorporation at the same position into an unmodified primer/template. The
      polymerase dissociated from the sites of the adducts at approximately the same
      rate that it dissociated from unmodified DNA. Correct nucleotide incorporation
      was favored both opposite and immediately after AF-dG. However, at both
      positions, dATP was the most rapidly misincorporated nucleotide. Misincorporation
      of dATP was more rapid than correct nucleotide incorporation both opposite and
      immediately after AAF-dG. These results are discussed in terms of the effects of
      AF and AAF adducts in vivo.

PMID- 8292605
TI  - Acceptor helix interactions in a class II tRNA synthetase: photoaffinity cross
      linking of an RNA miniduplex substrate.
AB  - The 875 amino acid class II Escherichia coli alanine tRNA synthetase
      aminoacylates hairpin minihelices and miniduplexes comprising complementary base
      pairs that reconstruct the acceptor helix of alanine tRNA. Aminoacylation is
      dependent upon a G3:U70 base pair in the tRNA acceptor stem. A synthetic RNA
      miniduplex with a phosphorothioate internucleotide linkage on the 5'-side of U70
      facilitated the stable attachment of a pendant benzophenone to the ribonucleotide
      backbone. The benzophenone-labeled duplex is active for aminoacylation.
      Irradiation of the labeled duplex produced a cross-linked RNA protein complex, in
      which the major site of RNA attachment is the segment between the class II
      defining sequence motifs 2 and 3. This segment spans a putative zinc-binding
      motif, which has been implicated in acceptor helix recognition, and is within a
      461 amino acid N-terminal fragment that was recently shown to have full activity
      for minihelix aminoacylation. These results, together with the X-ray
      crystallographic investigations of the class II aspartate tRNA synthetase
      tRNA(Asp) complex, suggest that the segment between motifs 2 and 3 in the 10
      class II synthetases contributes generally to the docking of tRNA acceptor
      helices. The sequence diversity of this segment implies that its mode of
      interaction with the acceptor helix is idiosyncratic to the class II enzyme.

PMID- 8292607
TI  - 3-Methyleneoctanoyl-CoA and 3-methyl-trans-2-octenoyl-CoA: two new mechanism
      based inhibitors of medium chain acyl-CoA dehydrogenase from pig kidney.
AB  - The medium chain acyl-CoA dehydrogenase catalyzes the FAD-dependent oxidation of
      a variety of acyl-CoA substrates to the corresponding trans-2-enoyl-CoA
      thioesters. This work identifies 3-methyleneoctanoyl-CoA and 3-methyl-trans-2
      octenoyl-CoA as representatives of a new class of mechanism-based inhibitor of
      the dehydrogenase. One equivalent of either compound generates an inactive
      reduced flavin species with low absorption at 450 nm and a shoulder at 320 nm
      suggestive of an N-5 adduct. Reduction is rapid with the 3-methylene analogue
      (10/s at 1 degree C), but comparatively slow for 3-methyl-trans-2-octenoyl-CoA
      (1.1 x 10(-4)/s, under the same conditions). The reduced species is very stable,
      but the adduct can be slowly displaced with a large excess of octanoyl-CoA. The
      reduced adduct resists oxidation by the facile one-electron oxidant of the
      dehydrogenase, ferricenium hexafluorophosphate. Evidence that both isomeric
      inhibitors generate the same reduced flavin species includes an essentially
      identical visible spectrum, the same kinetics of displacement using octanoyl-CoA,
      and the same mixture of products on HPLC after denaturation of the treated enzyme
      with trichloroacetic acid, methanol, or by boiling. Experiments with the
      corresponding shorter analogues of these inhibitors, 3-methylenebutanoyl-CoA and
      3-methyl-2-butenoyl-CoA confirm and extend these findings. These reduced adducts
      are less stable, allowing the dehydrogenase to catalyze the interconversion of
      the unconjugated 3-methylenebutanoyl-CoA to the more stable conjugated 3-methyl-2
      butenoyl-CoA thioester (Keq ca. 150). These data suggest that alpha-proton
      abstraction from the 3-methylene derivatives or gamma-proton removal from the 3
      methyl-2-enoyl analogues generates a common carbanionic intermediate which
      attacks oxidized flavin. As would be expected, the unconjugated 3-methylene
      derivatives are more effective inhibitors of the dehydrogenase than the
      thermodynamically more stable 3-methylenoyl analogues.

PMID- 8292606
TI  - Site-specific benzo[a]pyrene diol epoxide-DNA adducts inhibit transcription
      elongation by bacteriophage T7 RNA polymerase.
AB  - Benzo[a]pyrene, an extremely potent procarcinogen and mutagen, is metabolized to
      a variety of products, including the ultimate carcinogen 7,8-dihydroxy-9,10-epoxy
      7,8,9,10-tetrahydrobenzo[a]pyrene. This product of biotransformation reacts with
      DNA, forming a series of adducts principally at the N2 position of guanine that
      differ in their stereochemistry and exhibit unique biological properties. In
      order to gain a better understanding of the effects on RNA synthesis of these
      adducts, we used purified bacteriophage T7 RNA polymerase to transcribe a series
      of templates containing one of four stereoisomerically pure BPDE-guanine lesions-
      (+)-trans-,(-)-trans-,(+)-cis-anti-N2-BPDE-guanine--or no damaged bases. To
      construct suitable double-stranded oligodeoxynucleotides for these studies, we
      annealed an 11-mer containing a site-specific stereoisomerically pure N2-BPDE
      guanine adduct, a 37-mer, and a 10-mer to a complementary 58-base sequence of
      single-stranded DNA. The oligomers were ligated, purified, and reannealed. The
      resulting DNA template contained the promoter for T7 RNA polymerase and a BPDE
      adduct at position +16 following the transcription initiation site. The results
      of the transcription assays clearly demonstrate that each of the adducts inhibits
      elongation by T7 RNA polymerase, but they do so to significantly different
      extents, depending on the stereochemical characteristics of the BPDE-modified
      guanine. The order of inhibition is (+)-trans > (-)-trans > (+)-cis > (-)-cis,
      when the amount of full-length transcript for each is compared to that obtained
      for an unmodified template. Furthermore, premature termination of RNA synthesis
      occurs at or near the site of the BPDE lesion as evidenced by the formation of
      discrete, truncated transcripts. These results might be related to the fact that
      the pyrenyl moiety of the trans-BPDE adducts is situated in the minor groove of
      double-stranded DNA, but is quasi-intercalated into the double helix in the case
      of the cis stereoisomers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292608
TI  - Role of tyrosine 143 in lactate dehydrogenation by flavocytochrome b2. Primary
      kinetic isotope effect studies with a phenylalanine mutant.
AB  - Flavocytochrome b2 catalyzes the oxidation of lactate at the expense of
      cytochrome c. After flavin (FMN) reduction by the substrate, reducing equivalents
      are transferred one by one to heme b2, and from there on to cytochrome c. The
      crystal structure of the enzyme is known at 2.4-A resolution, and specific roles
      in catalysis have been assigned to active side chains. Tyr143 in particular,
      located at the interface between the flavodehydrogenase moiety and the heme
      binding domain, was thought to take part in substrate binding, as well as to
      orient the heme-binding domain for efficient electron transfer. A first study of
      the properties of a Tyr143Phe mutant showed that the major effect of the mutation
      was to decrease the rate of electron transfer from flavin to heme [Miles, C.S.,
      Rouviere-Fourmy, N., Lederer, F., Mathews, F.S., Reid, G.A., Black, M.T., &
      Chapman, S.K. (1992) Biochem. J. 285, 187-192]. In the present paper, we focus on
      the effect of the mutation on catalysis of lactate dehydrogenation. We report the
      deuterium kinetic isotope effects on flavin reduction as measured with stopped
      flow methods and on cytochrome c reduction in the steady-state using L-[2
      2H]lactate. For the wild-type enzyme, isotope effects on FMN reduction, D(kredF)
      and D(kredF)/Km), were 7.2 +/- 0.9 and 4.2 +/- 1.3, respectively, and for the
      Y143F mutant values of 4.4 +/- 0.5 and 3.9 +/- 1.1 were obtained. Calculations,
      from deuterium isotope effects, of substrate Kd values, combined with knowledge
      of kcat/Km values, lead to the conclusion that Tyr143 does stabilize the
      Michaelis complex by hydrogen bonding to a substrate carboxylate, as was
      postulated; but the mutation does not destabilize the transition state more than
      the Michaelis complex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292609
TI  - Photoaffinity labeling of cytochrome P450 2B4: capture of active site heme
      ligands by a photocarbene.
AB  - Spiro[adamantane-2,2'-diazirine], which produces adamantyl carbene upon
      photolysis, binds tightly to P450 2B4 (KS = 3.2 microM), giving a normal
      substrate binding difference spectrum. Irradiation of 2-[3H]adamantane diazirine
      at 365 nm in the presence of native, ferric P450 2B4 resulted in first-order
      photolysis (t1/2 = 1.8 min). The main product was 2-[3H]adamantanol, with about
      6% of the radioactivity covalently bound to P450 2B4. With the ferrous carbonyl
      form of P450 2B4, 2-adamantanol production decreased and protein labeling
      increased to 12%. When ferric cyanide 2B4 was used, 2-adamantanecarbonitrile was
      formed in addition to 2-adamantanol. The nitrile appears to have resulted from
      capture of the iron-bound cyanide ligand by the carbene. The use of multiple
      cycles of photolysis increased the percentage of protein labeling to 76%.
      Photolabeling was inhibited by known 2B4 substrates and inhibitors. Also, N
      demethylation of benzphetamine and generation of a substrate binding difference
      spectrum by benzphetamine were both inhibited stoichiometrically with the
      fraction of radiolabeled protein. The labeled protein was permanently converted
      to the high-spin state, as indicated by the characteristic change in the
      absorbance spectrum, demonstrating irreversible occupation of the substrate
      binding site by the adamantyl residue. Mild acid hydrolysis of radiolabeled 2B4
      at the five Asp-Pro bonds generated a 2-kDa peptide which carried 78% of the
      radioactivity. These results are interpreted as the result of the active site
      carbene reacting by three competing pathways: capture of the heme sixth ligand to
      yield either 2-adamantanol or 2-adamantanecarbonitrile, capture of an unbound
      active site water molecule to yield adamantanol, and covalent attachment to a
      protein residue. Thus, the P450 2B4 active site appears to contain at least one
      unbound water molecule in addition to the heme aquo sixth ligand, even when
      substrate is present.

PMID- 8292610
TI  - Endogenous antithrombin associated with microvascular endothelium. Quantitative
      analysis in perfused rat hearts.
AB  - A recirculating Langendorff heart preparation is used to characterize the
      endogenous antithrombin associated reversibly with murine vascular endothelium.
      Rat hearts are perfused clear of blood and then recirculated with a physiological
      salt solution. Addition of heparin educes antithrombin activity continuously into
      the perfusate during 6 min of recirculation. This process contrasts with a more
      rapid equilibration of the system as assessed by displacement of [125I]thrombin
      with hirudin or with a heparin-antithrombin mixture. Perfusion of washed hearts
      with [125I]factor Xa, which evidences no significant binding to the coronary
      endothelium, identifies a minor fraction of the endogenous antithrombin that
      reacts immediately with factor Xa, i.e., at a rate indicative of heparin
      enhancement. This rapid-reacting antithrombin is not reproducibly detected with
      [125I]thrombin, which binds preferentially to thrombomodulin in this system. The
      amount of antithrombin reacting rapidly with factor Xa is too low to detect as a
      burst of antithrombin activity eluted into the perfusate when the hearts are
      perfused with heparin. It is concluded that the murine myocardial
      microvasculature harbors at least two pools of antithrombin, the minor of which
      is in an activated configuration characteristic of association with heparin. The
      major pool is in a more slowly accessible compartment or configuration.

PMID- 8292611
TI  - Construction, expression, and properties of a recombinant chimeric human protein
      C with replacement of its growth factor-like domains by those of human
      coagulation factor IX.
AB  - The cDNA encoding a chimeric human protein C (PC), in which its epidermal growth
      factor-(EGF) like regions have been replaced with equivalent structures from
      human factor IX (fIX), was constructed and the gene product was expressed in
      human 293 cells. A molecular subpopulation of the recombinant chimeric protein (r
      [PC/delta EGF-1,2/delta fIXEGF-1,2]) was purified that contained the full
      complement (9 residues/mol) of gamma-carboxyglutamic acid (Gla). After conversion
      by thrombin to its activated form (r-[APC/delta EGF-1,2/delta fIXEGF-1,2]), this
      latter enzyme was found to possess approximately 10% of the activity of wild-type
      recombinant APC (wtr-APC) in an APTT assay. In assay systems employing purified
      components, the activity of the mutant enzyme toward prothrombinase cofactor Va
      (fVa) and tenase cofactor VIII (fVIII) was approximately 30% and < 10%,
      respectively, of that of wtr-APC. The chimeric protein displayed full reactivity
      with a Ca(2+)-dependent monoclonal antibody to the Gla domain of PC, yielding a
      C50 for Ca2+ that was very similar to that obtained with wtr-PC (ca. 3.7 mM).
      Titrations of the dependency on Ca2+ of the intrinsic fluorescence of r-[PC/delta
      EGF-1,2/delta fIXEGF-1,2] allowed calculation of a C50 value of 0.34 mM, again
      very similar to that of wtr-PC. As with wtr-PC, Ca2+ inhibited the thrombin
      catalyzed activation of r-[PC/delta EGF-1,2/delta fIXEGF-1,2] with aKi of 148
      microM, as compared to a Ki of 125 microM for wtr-PC. At a saturating level of
      Ca2+, activation of r-[PC/delta EGF-1,2/delta fIXEGF-1,2/] by the
      thrombin/thrombomodulin (thrombin/TM) complex occurred at approximately 70% of
      the rate of that of wtr-PC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292613
TI  - Mutagenesis of the phosphorylation site (serine 19) of smooth muscle myosin
      regulatory light chain and its effects on the properties of myosin.
AB  - A full-length cDNA of smooth muscle regulatory light chain was obtained and the
      recombinant regulatory light chain was expressed in an Escherichia coli
      expression system. The recombinant regulatory light chain was introduced into
      myosin or HMM using a subunit exchange strategy [Morita, J., Takashi, R., &
      Ikebe, M. (1991) Biochemistry 30, 9539-9545]. The recombinant wild-type
      regulatory light chain exhibited the same biological properties as the natural
      isolate, i.e., phosphorylation at Ser-19 by myosin light-chain kinase and
      phosphorylation-activated actomyosin ATPase activity. To clarify whether or not
      the activation of the ATPase by phosphorylation is simply due to the introduction
      of negative charge, we produced three mutant light chains. Two of them contain
      Ser-19 substituted by either Asp or Ala and the third contains Asp substituted
      for both Thr-18 and Ser-19. Incorporation of the Asp mutant partially activated
      actomyosin ATPase activity but the activation level was significantly lower than
      that by phosphorylation. The Asp/Asp mutant further activated actomyosin ATPase
      activity. On the other hand, the Ala mutant did not affect the ATPase activity.
      Incorporation of Asp mutant slightly affected the 10S-6S conformational
      transition and filament formation of myosin. The Asp/Asp mutant more
      significantly affected the 10S-6S conformational transition and filament
      formation of myosin. These results suggested that the activation of smooth muscle
      myosin requires the introduction of negative charge in the defined spacial
      position. Using Ser-19 deficient mutants, the effects of Thr-18 phosphorylation
      on myosin function was also studied. Actin-activated ATPase activity of myosin
      was significantly activated by phosphorylation of Thr-18.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8292612
TI  - Apolipoprotein J is associated with paraoxonase in human plasma.
AB  - Apolipoprotein J (apoJ)-containing high-density lipoproteins (HDL), isolated from
      human plasma by immunoaffinity chromatography, are associated with apoAI and a
      protein of approximately 44 kDa. In order to advance our understanding of apoJ's
      role in the vasculature, a comprehensive investigation was performed to identify
      and characterize this 44-kDa protein and to study its interaction with apoJ. The
      44-kDa protein, a monomeric glycoyslated polypeptide, was identified by N
      terminal sequencing as serum paraoxonase. Paraoxonase exists in two oxidation
      states: one contains all free cysteines while the other has one disulfide bond
      between Cys42 and Cys284. Northern analysis of eight human tissues shows
      paraoxonase message present only in the liver. The majority of apoJ/paraoxonase
      HDL are 90-140 kDa; however, not all of the plasma paraoxonase is associated with
      apoJ. The specificity of the apoJ/paraoxonase interaction, inferred by the
      constant mole ratio of the two proteins in affinity-purified apoJ-HDL, is
      confirmed in direct binding assays. For purified proteins, there is more than a 5
      fold increase in the apparent affinity of apoJ for immobilized paraoxonase as the
      paraoxonase coating concentration is increased from 0.5 to 2.0 micrograms/mL.
      Both oxidation states of paraoxonase bind to apoJ with equal affinity. Our data
      combined with other evidence suggest that the plasma link of apoJ with
      paraoxonase will be implicated as a predictor of vascular damage.

PMID- 8292614
TI  - Binding and elution of EGTA to anion exchange columns: implications for study of
      (Ca+Mg)-ATPase inhibitors.
AB  - EGTA bound to DEAE-Sephadex and DEAE-cellulose at low ionic strength in the
      presence and absence of applied protein. It remained bound when the column was
      washed at low ionic strength, but was eluted as the ionic strength was increased.
      The amount of EGTA recovered at high ionic strength was 60 to 90% of that applied
      to the column. At the peak of its elution, the concentration of EGTA in the
      eluted fractions was 25 mM, over 10-fold higher than the concentration of EGTA
      applied to the column. Eluted fractions containing EGTA inhibited the (Ca+Mg)
      ATPase by two mechanisms: (1) by chelating the Ca and (2) by affecting activity
      even when the free Ca was held constant. We suggest that at least some of the
      inhibitory effects previously attributed to a cytoplasmic inhibitor of the
      (Ca+Mg)-ATPase may in fact be due to contaminating amounts of EGTA.

PMID- 8292615
TI  - Na(+)-Ca2+,K+ exchange in bovine retinal rod outer segments: quantitative
      characterization of normal and reversed mode.
AB  - Ca2+ homeostasis of bovine retinal rod outer segments is maintained through Na(+)
      Ca2+,K+ exchangers and cGMP-gated channels in the plasma membrane. It has
      recently been demonstrated that both proteins are associated. This novel finding
      allowed us to investigate quantitatively normal and reversed mode Na(+)-Ca2+,K+
      exchange in rod outer segment membrane vesicles and reconstituted proteoliposomes
      both containing exchangers in rightside-out and inside-out orientations. Addition
      of Na+ activated both normal and reversed mode exchange; if, however, initially
      Ca2+ from vesicles containing inside-out oriented exchangers has been released by
      activation of the associated channels, only normal mode exchange was observed
      upon addition of Na+. Using this approach, the fractions of vesicles containing
      rightside-out and inside-out oriented exchangers were about similar in these
      vesicle preparations. Normal and reversed mode exchange had similar Na+
      concentrations of about 70 mM for half maximal activation (in the presence of 115
      mM K+) and cooperativity parameters, nHill, of about 2.0. Furthermore, both modes
      were electrogenic, and showed only little Na(+)-Ca2+,K+ exchange in the absence
      of K+. The two modes of exchange differed, however, in the maximal exchange rate,
      the normal mode being about twice as fast as the reversed mode.

PMID- 8292616
TI  - Localization of Na+/K(+)-ATPase in the bovine corneal endothelium.
AB  - A mouse monoclonal antibody has been used to localize Na+/K(+)-ATPase in the
      bovine corneal endothelium. The specificity of the antibody was demonstrated by
      reaction with a single protein of molecular mass 100 kDa on Western blots and
      immunoprecipitation of a complex consisting of 100 kDa and 50 kDa subunits.
      Treatment of the immunoprecipitated antigen with Peptide N-Glycanase F produced
      no change in the molecular mass of the 100 kDa protein, but resulted in a
      progressive decrease in the molecular mass of the 50 kDa subunit, to yield a core
      protein of molecular mass about 33 kDa. The pattern of deglycosylation suggested
      the presence of three N-linked glycans attached to the 33 kDa protein core. These
      results were consistent with the antibody being specific for the alpha subunit of
      the Na+/K(+)-ATPase. Immunocytochemical studies at the light and electron
      microscopic level demonstrated antibody binding to both the basal and lateral
      membranes of bovine corneal endothelial cells. This suggested a baso-lateral
      distribution of Na+/K(+)-ATPase in these cells, rather than the previously
      proposed lateral membrane-only distribution.

PMID- 8292617
TI  - Chronic ethanol intoxication induces adaptive changes at the membrane
      protein/lipid interface.
AB  - Modifications were found to occur at the membrane protein/lipid interface of
      liver microsomes in animals that had been subjected to chronic ethanol ingestion.
      The effects were revealed by probing this region with 1,6-diphenyl-1,3,5
      hexatriene (DPH), trimethylammonium-DPH (TMA-DPH) and DPH attached to the sn-2
      chain of phosphatidylcholine (1-palmitoyl-2-[[2-[4-(6-phenyl-trans-1,3,5
      hexatrienyl) phenyl]ethyl]carbonyl]-3-sn-phosphatidylcholine, DPH-PC). In intact
      membranes, it was found that the decay of the excited state was heterogeneous,
      this being modeled by fitting the data to a fluorescence lifetime distribution.
      The full-width of the distribution at half-maximum, which relates to the degree
      of excited state environmental heterogeneity, increased for each fluorophore, as
      a result of chronic ethanol treatment. For TMA-DPH and DPH the excited state
      heterogeneity could have arisen from, (i) the protein/lipid interface and (ii)
      varied degrees of water penetration into the lipid, due to the ability of these
      fluorophores to sample along the bilayer normal. By contrast, the DPH in DPH-PC,
      due to its tethering, was only able to sample the heterogeneity at the
      protein/lipid interface, as confirmed by a homogeneous decay in vesicles of
      microsomal lipid extracts. The increased degree of DPH-PC fluorescence decay
      heterogeneity in microsomes from chronic ethanol-treated animals as compared to
      controls, was found to persist in vesicles of extracted lipids, when
      apocytochrome C was included in the vesicle preparations as a model protein. This
      effectively eliminated a protein modification from being responsible and
      indicated that a chronic-ethanol induced alteration in the lipids was being
      expressed in the form of a physico-chemical modification at the protein/lipid
      interface. The degree of DPH-PC environmental heterogeneity was also directly
      increased by ethanol, however, membranes from chronic ethanol-treated animals
      were resistant to this effect, showing that the phenomenon of 'membrane
      tolerance' extends to the membrane protein/lipid interface.

PMID- 8292618
TI  - Tertiary amines as antagonists of both the luminal and cytosolic K(+)-site of
      gastric H,K-ATPase.
AB  - Tertiary amines like imidazole and triallylamine lower the apparent affinity of
      K+ in the ATP hydrolysis reaction of pig gastric H,K-ATPase in a pH and amine
      concentration dependent way. The mechanism and sidedness of this effect was
      studied by analyzing the partial reactions of the enzyme in both leaky and ion
      tight vesicles. In leaky vesicles Tris and Hepes had nearly no effect on the
      apparent Km for K+ in the ATPase reaction, but imidazole (Ki = 13 mM) and
      triallylamine (Ki = 1.6 mM) markedly decreased the K+ affinity. The steady-state
      ATP-phosphorylation level in the absence of K+ was not or only slightly affected
      by these compounds. The reduction of the ATP-phosphorylation level by K+,
      however, again depended on both the type and concentration of tertiary amine
      used. A comparable K(+)-amine antagonism was observed in the dephosphorylation
      reaction. In tightly sealed vesicles, where no activation of K+ at the luminal
      side could occur, K+ reduced the affinity for ATP in the phosphorylation
      reaction. Triallylamine counteracted this effect. The K(+)-activated p
      nitrophenylphosphatase activity in these ion-tight vesicles also showed a K(+)
      triallylamine antagonism. Inhibition of H,K-ATPase activity in these vesicles by
      triallylamine was immediate (with nigericin present in order to allow
      intravesicular K+ activation), suggesting the transmembrane feature of this
      inhibition. These results indicate that tertiary amines decrease the affinity for
      K+ at both luminal and cytosolic binding sites by interaction at the cytosolic
      side of the membrane. This results in shifts in the equilibrium of both the
      E1.H<==>E1.K transition and in the dephosphorylation reaction, E2-P-->E2.K.

PMID- 8292619
TI  - Protein endocytosis by a kidney tubule suspension: metabolic requirements.
AB  - Endocytosis in the renal tubular cell is a permanent process serving the role of
      saving nitrogen from plasma peptides that are continuously cleared away by kidney
      glomerulus. Since small proteins appear in urine after strenuous exercise, it was
      hypothesized that renal ischemia impairs the tubular endocytic reabsorption of
      proteins. The aim of this paper is to describe a simple in vitro model of renal
      endocytosis and to use it in studies of endocytic metabolic requirements. The
      results show that rabbit renal proximal tubules in suspension are able to take up
      125I-lysozyme, as well as RITC-lactalbumin. The fluorescent protein was taken up
      only by the ends of the everted tubule fragments, and accumulated into
      intracellular vesicles, demonstrating the luminal pathway of endocytosis. The
      amount of 125I-lysozyme taken up was equivalent to that taken up by isolated
      perfused tubules (Nielsen et al. (1986) Am. J. Physiol. 251, F822-F830). Anoxia
      decreased 12-fold the intracellular accumulation of 125I-lysozyme; however, the
      time-course of inhibition shows that only the late steps of endocytic
      accumulation are energy-dependent. Substrate deprivation studies suggest a
      specific role of glucose to sustain endocytosis. Lastly, renal uptake of 125I
      lysozyme was shown to be strongly depressed by chloroquine, an alkalinizing agent
      of endosomes and lysosomes. We conclude that (1) renal tubules in suspension are
      a satisfactory model for endocytic studies in kidney; (2) suppressing oxygen and
      substrate supplies to kidney impairs endocytic tubular reabsorption of proteins.

PMID- 8292620
TI  - The cGMP-inhibitable phosphodiesterase modulates glucose transport activation by
      insulin.
AB  - To assess the role of the cGMP-inhibitable phosphodiesterase (cGI-PDE) in the
      action of insulin on glucose transport, adipocytes from young, lean rats were
      preincubated for 20 min at 37 degrees C with and without OPC 3911, a specific
      inhibitor of cGI-PDE, and 3-O-methylglucose uptake was measured. Insulin
      stimulated glucose transport was impaired by OPC 3911 (approximately 15%) and
      this impairment became more pronounced in the presence of the degradable cAMP
      analogue 8-bromo-cAMP (approximately 45%). This analogue alone did not
      significantly decrease glucose transport. Furthermore, insulin sensitivity was
      impaired by the combination of OPC 3911 and 8-bromo-cAMP. Maximal insulin
      stimulated glucose transport in adipocytes from aging, obese rats was affected
      similarly by OPC 3911 and 8-bromo-cAMP, suggesting that cGI-PDE activity is not
      markedly altered in this insulin-resistant state. In conclusion, cGI-PDE exerts a
      modulating effect on the stimulatory action of insulin on glucose transport. This
      effect is particularly pronounced when the cellular cAMP levels are elevated.

PMID- 8292621
TI  - Binding of HDL to basolateral membranes of the renal cortex. Evidence for two
      components in the HDL-membrane association.
AB  - The binding of porcine 125I-HDL to purified basolateral membrane fractions
      isolated from pig kidney cortex displays two categories of sites, one with high
      affinity ((Kd = (3.0 +/- 0.7) x 10(-9) M) and low capacity (Bmax = 52 +/- 32
      ng/mg proteins) another with low affinity (Kd = (5.3 +/- 0.7) x 10(-8) M) but a
      higher capacity (Bmax = 795 +/- 115 ng/mg proteins). Binding was competitively
      inhibited to the same extent by unlabeled HDL from swine, human or rat,
      demonstrating an absence of species specificity. Porcine LDL partially competed
      for binding even in the presence of 30 mM EDTA which prevents apo B/E specific
      binding. Membrane proteins solubilized with CHAPS were analyzed by
      electrophoresis followed by ligand blotting using porcine 125I-HDL and 125I-apoAI
      HDL to show that HDL bound to two proteins of respective molecular masses 120 +/-
      2 and 95 +/- 9 kDa. 125I-apoAI associated mostly with the 95 kDa protein. A 100
      fold excess of unlabeled HDL greatly decreased binding to the 95 kDa protein but
      less to the 120 kDa protein. We conclude that part of HDL binding occurs through
      the lipid moiety, while another is the result of a specific interaction between
      apoAI and a membrane protein of 95 kDa.

PMID- 8292622
TI  - Real-time measurements of chemically-induced membrane fusion in cell monolayers,
      using a resonance energy transfer method.
AB  - Fusion of mouse melanoma cells grown in monolayers has been directly monitored by
      fluorescence resonance energy transfer between fluorescein and rhodamine probes
      attached to octadecanoic acid. Various poly(ethylene glycol)s (PEG), either alone
      or in combination with amphipathic molecules, have been used as fusogens. Fusion
      starts at a maximum rate as soon as PEG is removed from the medium and reaches a
      plateau after 20-30 min. Both the initial rate and extent of fusion have been
      recorded for each experiment. The extent of fusion shows in general a positive
      correlation with the initial rate, although PEGs with different molar masses
      appear to induce fusion at different rates, but to a similar extent. A good
      correlation has been found between the extent of fusion, as measured by
      fluorescence, and the 'fusion index' computed from cell and nucleus counting; a
      calibration curve is provided for the interconversion of both parameters. Optimum
      fusion values are obtained with 50% (w/v) PEG 1500. The effect of pre-treatments
      with surfactants (Triton X-100, sodium dodecylsulphate) on PEG-induced fusion has
      also been tested. Sodium dodecylsulphate, but not Triton, enhances considerably
      both the rate and extent of cell fusion. The in situ generation of the
      amphipathic molecule diacylglycerol, through the catalytic activity of a
      phospholipase C, also enhances significantly the fusion parameters. These results
      are in good agreement with previous studies based on syncytia counting.

PMID- 8292623
TI  - Proton ejection as a major feature of the Ca(2+)-pump.
AB  - H+ ejection and Ca2+ uptake promoted by the sarcoplasmic reticulum (SR) Ca(2+)
      pump are similarly stimulated by millimolar Mg2+. This cannot be assigned to
      enhanced Ca2+ uptake and H+ displacement from internal metal binding sites since:
      (1) loading SR vesicles with high Mg2+ concentrations does not impair H+
      ejection; (2) loading SR vesicles with Mn2+ does not depress H+ ejection
      occurring during Mn2+ uptake; (3) H+ ejection occurs even when Ca2+ accumulation
      inside the vesicles is prevented with Ca2+ ionophores. It is concluded that the
      Ca(2+)-pump promotes an active Ca2+/H+ countertransport stimulated by Mg2+.
      Finally, a mechanism for Ca2+ translocation is proposed in basic physico-chemical
      terms.

PMID- 8292624
TI  - Phosphate, nitrendipine and valinomycin increase the Ca2+/ATP coupling ratio of
      rat skeletal muscle sarcoplasmic reticulum Ca(2+)-ATPase.
AB  - Nitrendipine and valinomycin act synergistically to stimulate ATP-dependent Ca2+
      accumulation by rat skeletal muscle sarcoplasmic reticulum vesicles 3-fold. The
      stimulation is not caused by activation of the Ca(2+)-ATPase or by inhibition of
      the sarcoplasmic reticulum Ca2+ channel, but is due to an increased efficiency of
      transport by Ca(2+)-loaded vesicles. At low Ca2+ concentrations,
      nitrendipine+valinomycin inhibits Ca2+ uptake by increasing the Ca2+ KM but does
      not effect equilibrium Ca2+ binding to the Ca(2+)-ATPase (Kd = 0.75 microM). In
      the presence of 50 mM phosphate, nitrendipine+valinomycin increases the steady
      state coupling ratio (Ca2+ accumulated per ATP hydrolyzed) from 0.6 to 1.9 by
      decreasing the rate of ATP hydrolysis by 72%, while reducing the Ca2+
      accumulation rate by only 13%. The rates of both passive and Ca(2+)-ATPase
      mediated Ca2+ release are reduced by nitrendipine+valinomycin. The data indicate
      that nitrendipine and valinomycin act directly on the Ca(2+)-ATPase to decrease
      the ATP hydrolysis rate, increase the Ca2+ KM, decrease Ca2+ efflux, and increase
      the Ca2+/ATP coupling ratio of Ca(2+)-loaded vesicles.

PMID- 8292625
TI  - DNA transfection mediated by cationic liposomes containing lipopolylysine:
      characterization and mechanism of action.
AB  - The ability of a polycationic lipid, lipopoly(L-lysine) (LPLL), to mediate
      efficient DNA transfection depended on scraping of the treated cells (Zhou et al.
      (1991) Biochim. Biophys. Acta 1065, 8-14). It was found that the mechanical
      treatment could be avoided by including a helper lipid to the liposome
      composition. Among the helper lipids tested, a hexagonal phase forming lipid,
      dioleoylphosphatidylethanolamine (DOPE), gave rise to the highest activity. The
      transfection efficiency was further optimized by varying the lipophilicity of the
      LPLL and the ratio of the cationic liposome to DNA. Transfection activity of the
      optimal DNA-liposome complexes was enhanced by up to 6-fold if cells were
      pretreated with agents interfering with the process of endocytosis. Meanwhile,
      pretreatment of cells with a peptide which inhibits membrane fusion decreased the
      activity by about 60%. These results indicated that DNA-liposome complexes are
      taken up by an endocytosis mechanism and that cytoplasmic delivery of DNA
      involves a fusion-related event probably in the endosome compartment. The
      transfection process was visualized by thin-section electron microscopy. It was
      found that the complexes entered the cytoplasm mainly by destabilizing endosomes
      and occasionally by penetrating through the plasma membrane. Therefore, our
      findings differ from a previous hypothesis which suggests that transfection is
      mediated by fusion of the liposomes with the plasma membrane of the treated
      cells.

PMID- 8292626
TI  - Voltage gating of porins from Haemophilus influenzae type b.
AB  - The major outer membrane protein of Haemophilus influenzae type b (Hib) is porin
      (M(r) 37,782; 341 amino acids). Porins were purified from Hib strains
      representative of the three outer membrane protein subtypes 1H, 2L and 6U,
      reconstituted into artificial planar bilayers, and tested for their voltage
      dependency. At membrane potentials of 50-80 mV, individual Hib 2L and 6U porin
      channels showed a high probability of undergoing a reversible change to one of
      several lower conducting substates. Such behaviour was not observed for Hib 1H
      porin with transmembrane potentials up to 80 mV. The voltage dependence of Hib 2L
      and 6U porins was asymmetric: it occurred at only one polarity. The asymmetry was
      also observed for membranes with numerous porins incorporated, suggesting that
      Hib porin inserted asymmetrically into the bilayer. At macroscopic levels the
      voltage gating reduced the conductance by 25-50%, implying that the channels
      closed only partially. Hib 2L porin differs from Hib 1H porin by the substitution
      Arg166Gln and Hib 6U porin differs from Hib 1H porin by substitutions at ten
      amino acids including the change Arg166Leu. We conclude that substitutions at
      Arg166 residue, which is localized to surface-exposed loop number four, are
      associated with a lowered threshold potential for the voltage gating of Hib
      porin. This surface-exposed loop may play some role in the conformational changes
      that occur during voltage gating.

PMID- 8292627
TI  - External surface and lamellarity of lipid vesicles: a practice-oriented set of
      assay methods.
AB  - Three methods are presented for the determination of external surface of large
      lipid vesicles of different lamellarity with 2% absolute accuracy. These methods
      (referred to as EPR, NBD and TNBS assays) use different marker lipids which
      provide signals (electron paramagnetic resonance, fluorescence of N-(7-nitrobenz
      2-oxa-1,3-diazol-4-yl) residues, and UV absorption increase of 2,4,6
      trinitrobenzenesulfonic acid after reaction with aminolipids, respectively). The
      signals change upon addition of different membrane-impermeant reagents due to
      reaction with marker lipids at the external vesicle surface. They were applied to
      the same vesicle samples, including unilamellar and multilamellar vesicles, both
      at two different lipid compositions. External surface data matched for the three
      assays within 2%, but only after appropriate redesign or adaptation of so far
      published procedures. Main improvements related to slow influx of reagents (TNBS
      and NBD assays) or to redistribution of marker lipids (EPR assay), obscuring
      determination of outer vesicle surface from fast reaction between reagent and
      readily accessible marker lipids. Furthermore, suitable strategies were found to
      obtain accurate 100% values (reaction of all marker lipids present), required to
      relate external vesicle surface to total surface. This included corrections for
      light scattering (NBD assay) and for turbidity (TNBS assay). These three methods
      appear to close a gap in the methodology to determine external surface of
      vesicles for typical practical needs. In particular, the reliability range of the
      NBD assay could be extended to marker lipid densities as low as 1 marker lipid
      per 3000 lipids.

PMID- 8292628
TI  - Effect of divalent cations on lipid organization of cardiolipin isolated from
      Escherichia coli strain AH930.
AB  - Escherichia coli strain AH930 is a lipid biosynthetic mutant, which is unable to
      synthesize phosphatidylethanolamine. Instead it produces large amounts of
      phosphatidylglycerol and cardiolipin and has an absolute requirement for certain
      divalent cations. Cardiolipin was isolated from this mutant strain and its
      interaction with divalent cations was studied by various biophysical techniques.
      Monolayer measurements showed that the cations decrease the molecular surface
      area of cardiolipin in the order Ca2+ approximately Mg2+ > Sr2+ > Ba2+. 31P-NMR
      and X-ray diffraction measurements demonstrated a comparable sequence for the
      ability of the cations to promote HII phase formation in dispersions of the E.
      coli cardiolipin: Ca2+ and Mg2+ induced HII phase formation at 50 degrees C, Sr2+
      at 75 degrees C, while Ba2+ was found to be unable to promote HII phase formation
      in the temperature range measured. Furthermore, all divalent cations were found
      to increase the temperature at which the transition to the liquid-crystalline
      phase takes place, which was below 5 degrees C for the lipid in the absence of
      divalent cations. In the presence of Sr2+, Mg2+ and Ba2+ and at 25 degrees C two
      lamellar phases were observed, one corresponding to a liquid-crystalline phase,
      the other to either a gel or a crystalline phase. In the presence of Ca2+ at 25
      degrees C and even at 45 degrees C no evidence for a liquid-crystalline phase was
      obtained and only a crystalline phase could be observed. The ability of the
      different cations to promote HII phase formation in the isolated E. coli
      cardiolipin was found to correlate with their ability to support growth of the
      mutant strain (De Chavigny, A., Heacock, P.N., Dowhan, W. (1991) J. Biol. Chem.
      266, 5323-5332), suggesting that cardiolipin with divalent cations can replace
      the role of phosphatidylethanolamine in the mutant strain, and that this role
      involves the preference of these lipids for organization in non-bilayer lipid
      structures.

PMID- 8292629
TI  - Do the long fatty acid chains of sphingolipids interdigitate across the center of
      a bilayer of shorter chain symmetric phospholipids?
AB  - Novel cerebroside sulfate (CBS) spin labels containing long chain C24 or C26
      fatty acids with a nitroxide spin label on the 22nd carbon were synthesized and
      used to investigate the ability of the long fatty acid chains of
      glycosphingolipids to interdigitate across the center of a non-interdigitated
      bilayer of phospholipids formed of symmetric saturated or unsaturated shorter
      fatty acid chain species, in the presence or absence of cholesterol. The motion
      of these long chain spin labels incorporated at 1 mole% in
      dimyristoylphosphatidylcholine (diC14-PC), dipalmitoylphosphatidylcholine (diC16
      PC), distearoylphosphatidylcholine (diC18-PC), dibehenoylphosphatidylcholine
      (diC22-PC), spingomyelin (SM), 1-stearoyl-2-oleoylphosphatidylcholine (18:0.18:1
      PC), and dimyristoylphosphatidylethanolamine (diC14-PE) was compared to that of
      CBS spin labels containing stearic acid spin labeled at the 5th carbon and at the
      16th carbon. The results indicated that the C26 chain is interdigitated in the
      gel phase of diC14-PC, diC16-PC, SM, and possibly diC18-PC, but not diC14-PE, and
      the C24 chain may interdigitate in diC14-PC but not in the other phospholipids.
      Thus in order to interdigitate across the center of gel phase bilayers, the long
      acyl chain of the sphingolipid probably must be long enough to nearly span the
      phospholipid bilayer. The inability to interdigitate in diC14-PE is likely due to
      the close packing of this lipid in the gel phase. The C26 chain may also be
      interdigitated in these lipids in the presence of cholesterol at low
      temperatures. However, at physiological temperatures in the presence of
      cholesterol and in the liquid-crystalline phase of all the lipids, the results
      indicate that the long acyl chain of the glycosphingolipid is not interdigitated,
      but rather must terminate at the bilayer center. This may force the carbohydrate
      headgroup of the glycosphingolipid farther above the bilayer surface, allowing it
      to be recognized better by various carbohydrate binding ligands and proteins.

PMID- 8292630
TI  - Depth profiling of dibucaine in sarcoplasmic reticulum vesicles by fluorescence
      quenching.
AB  - The location of molecules of the local anesthetic dibucaine in sarcoplasmic
      reticulum vesicles (SRV) was determined using the quenching of its intrinsic
      fluorescence by iodide and by nitroxide-labeled stearic acids (SASL) with the
      nitroxide group at different positions of the fatty acyl chain. The molar ratios
      of dibucaine to Ca(2+)-ATPase in the samples were less than 1. The acid-base
      titration of membrane bound dibucaine revealed a pK of 9.1, showing a negligible
      shift upon binding. The quenching data were obtained at pH 6.8 and are therefore
      related to protonated dibucaine. Quenching by iodide showed SRV-bound dibucaine
      to be more protected from collisions with iodide anion than dibucaine in buffer
      or even in neutral micelles. This shows the influence of negatively charged
      lipids in keeping iodide away from the ionic diffuse layer of the membrane
      surface where the dibucaine tertiary amine might be located. Analysis of the SASL
      quenching data indicates that dibucaine molecules are at a shallow position in
      the membrane bilayer. Their average depth was found to be at most that of the
      fourth carbon atom of the fatty acyl chain. The results do not exclude a
      preferential site for dibucaine in Ca(2+)-ATPase, but if there is such site it
      must be located at the protein/lipid interface.

PMID- 8292631
TI  - Cloning of the cDNA and the genomic DNA of the mouse angiotensin II type 2
      receptor.
AB  - Of the two major isoforms of the angiotensin II receptors, type 1 (AT1) and type
      2 (AT2), little is known about the structure and features of AT2. We cloned a
      mouse AT2 cDNA from a mouse fetus cDNA library and an AT2 genomic DNA from a
      129SV mouse genomic DNA library. The amino acid sequence of the mouse AT2 (363
      residues) deduced from a mouse cDNA clone showed seven membrane-spanning domains.
      Amino acid identity of the mouse AT2 with mouse AT1 is 37%, and 98% with rat AT2.
      The genomic DNA (4.4 kb) contained three exons and two introns and the entire
      coding region was contained in the third exon.

PMID- 8292632
TI  - Assailants and victims: a comparative study of male wife-beaters and battered
      males.
AB  - Eighteen male wife-beaters were compared with 19 battered males concerning their
      background, history of addiction and present social situation, as well as present
      violence. The two groups of males had a very similar background including
      violence in their parental home. Alcohol and drug problems were common, the males
      generally belonged to the lower social classes and the number of divorcees was
      large. Many of the battered males had abused someone and the male batterers had
      been victimized themselves. It is concluded that the roles as victims and
      assailants vary among these men. The same background and precipitating factors
      will predestine the male to be a batterer or to be battered, but most probably
      both.

PMID- 8292633
TI  - Demographic, medical history and sexual correlates of HIV seropositive methadone
      maintained women.
AB  - Beginning in January 1989, consecutive female admissions to the ARTC MMTP Clinics
      in NYC were interviewed about their medical, drug, sexual and social experiences
      during 6 distinct historical years. Bloods were drawn and each sample tested for
      HIV via ELISA and Western Blot analysis. The data for 256 females was analyzed.
      The sample was predominantly Black (56%) and Hispanic (36%). Fifty-four percent
      (140) were between the ages of 31 and 40; 35% (91) were between the ages of 18
      and 30; and 10% (27) were 41 or older. The majority, 179 (69%), had less than a
      high school education, while 79 (31%) had a high school education or greater. The
      seropositivity for this sample of females was 60.4%. Aside from the common types
      of illnesses often seen in gay men infected with the HIV virus (i.e., pneumonia,
      night sweats, sore throat and swollen glands) our sample of females presented
      with symptoms such as abnormal discharges from the vagina, infections or
      abscesses of the veins, kidney or bladder infections, bleeding from the bowels
      and hepatitis infections. The most commonly reported risk factors among our
      sample of HIV positive females were sharing injecting materials (38%); injecting
      drugs in the veins (37.2%); dividing an injection (24.3%); and blood transfusions
      (10.9%). Of our HIV positive females, 42 of 97 (43.3%) reported having sex with a
      man they shared needles with only one time so that having sex with a man who is
      potentially infected with the HIV virus only once may be enough for a female to
      seroconvert. One limitation of this data is that there is no knowledge of when
      the HIV positive women seroconverted. Some of the behaviors reported could be due
      to exposure to AIDS education, and not to the knowledge to their HIV serostatus.

PMID- 8292634
TI  - Medical disorders in a cohort of New York city drug abusers: much more than HIV
      disease.
AB  - We evaluated the medical histories, drug abuse patterns, sexual behaviors,
      serological studies for syphilis and hepatitis B infection and other laboratory
      studies in 1780 patients enrolled in New York City drug treatment clinics in
      1987. HIV serology was available for 168 patients. Nearly seventy-five percent
      had at least one medical disorder and 57% one abnormal laboratory parameter. A
      history of gonorrhea, hepatitis B infection, pneumonia, and anemia was reported
      in 28%, 23%, 21%, and 20.7% of the patients, respectively. Fifty-seven percent of
      168 patients tested HIV seropositive and 16% of 1,780 patients were tuberculin
      reaction positive. Given the considerable prevalence of medical disorders, in
      which early identification and intervention is possible, serious consideration
      should be given to extend the scope of drug abuse services to include primary
      medical care services targeted at the medical sequelae of drug abuse, and medical
      disorders not directly associated with either HIV disease or drug abuse.

PMID- 8292635
TI  - Drug abuse treatment programs as centers for HIV-related research and treatment.
AB  - The Observational Data Base (ODB) is a multicenter, longitudinal effort of the
      Community Programs for Clinical Research in AIDS (CPCRA) designed to collect HIV
      related data on a large number of HIV-infected patients receiving primary care
      from community based physicians and health care groups. Over 400 patients from
      the Addiction Research and Treatment Corporation have enrolled in the ODB.
      Compared to the remainder of the CPCRA, ARTC ODB enrollees are more likely to be
      female, African American or Hispanic and to have injectable drug use and
      heterosexual contact with an injectable drug user as risk factors. The ARTC ODB
      patient profile closely resembles the fastest growing segments of the AIDS
      epidemic.

PMID- 8292636
TI  - Public policy statement on clinical applications of the nicotine patch.

PMID- 8292637
TI  - Public policy statement on core benefit for primary care and specialty treatment
      and prevention of alcohol, nicotine and other drug abuse and dependence.

PMID- 8292638
TI  - Medical evaluation of African American women entering drug treatment.
AB  - This study examined the records of 252 admissions to an inpatient drug
      rehabilitation program for African American women between July 1989 and July 1991
      to determine the prevalence and treatability of the medical conditions found on
      screening evaluation. All but 0.7% of subjects were on General Relief, Medicare,
      Medicaid, or had no payment source. The results showed a high prevalence of
      problems related to life style such as sexually transmitted diseases, anemia, and
      dental disease. Significant medical illness such as heart disease, abdominal
      surgical conditions, and breast masses were also found along with a high level of
      somatic discomfort of a subacute nature. Only 58% of patients referred to
      specialists kept the initial appointment. These results suggest that medical
      evaluation of impoverished African American women seeking rehabilitation for
      addiction may reveal many other health problems but that non-compliance severely
      limits the effectiveness of treatment. The role of the medical screening
      evaluation in determining fitness to participate in an inpatient program,
      detecting undiagnosed medical conditions, and patient education is discussed.

PMID- 8292639
TI  - Diminished illicit drug use as a consequence of long-term methadone maintenance.
AB  - In the twenty-five years since its introduction as a treatment for opiate
      addiction, methadone maintenance has generated considerable controversy regarding
      both its appropriateness as a treatment modality and its efficacy in diminishing
      opiate abuse. Given current concerns regarding the spread of HIV amongst IV drug
      abusers, the role of methadone maintenance may be more important than ever. The
      present study was designed to examine continued illicit substance abuse by 229
      patients enrolled in methadone treatment as a function of time in treatment
      (three months to over 10 years). Patients' urinalysis results collected over a 3
      month period indicated that (a) cocaine use is a problem amongst methadone
      maintained individuals and does not appear to be related to length of time on the
      program, (b) cocaine use did not lead to escalated opiate and other illicit drug
      abuse, and (c) opiate abuse decreased significantly with time in treatment.
      Specifically, while 35% of the patients enrolled for less than 12 months were
      opiate free for the 3 month period, that value increased to 71% for patients
      enrolled for more than 4 years, and 85% for patients remaining in treatment for
      over 10 years. These results based on urinalysis support the conclusion of Ball
      and Ross (1991), based on ASI scores and criminality data, that methadone is an
      effective treatment modality for opiate addicted individuals.

PMID- 8292640
TI  - Medical maintenance: a pilot study.
AB  - In a one year study, 130 methadone maintained subjects with a six month history
      of good treatment performance were assigned randomly to an experimental condition
      of one monthly non-random urine screen, one monthly counseling session, one
      monthly doctor visit, two times per month methadone pick up, a quarterly true
      random urine screen and participation in a diversion control program or to a
      control condition of staying under standard conditions for six months and then
      being transferred to the experimental condition for six months. Results of urine
      screens and scores on the Addiction Severity Index (ASI) at entrance and six
      month intervals showed no differences between groups. Three out of four subjects
      completed the year in good standing. Subject satisfaction was such that the IRB
      judged that return to standard conditions would be a hardship. Experimental
      conditions were cheaper such that resources freed up could be applied to the HIV
      epidemic.

PMID- 8292641
TI  - Reliability of the Self-Administered Alcoholism Screening Test (SAAST) in
      psychiatric inpatients.
AB  - Identification of alcohol abuse in psychiatric patients is essential, since it
      can confuse the clinical picture and complicate treatment. The utility and
      reproducibility of the Self-Administered Alcoholism Screening Test (SAAST) was
      assessed in 236 acutely ill psychiatric patients. Both an initial SAAST given at
      admission, and a second SAAST given shortly before discharge, were completed by
      173 (73%) patients; significant correlation (r = 0.85) was found between scores
      on SAAST 1 and SAAST 2. Only 41 (17%) patients were unable or refused to complete
      the initial SAAST and the majority of these received a schizophrenia diagnosis.
      SAAST scores were also significantly correlated with the clinical assessments and
      histories. Most (76%) patients with a current or past history of alcohol abuse
      scored in the "alcoholic" (> or = 8) range on one or both SAASTs. Men were almost
      twice as likely as women to have a history of alcohol abuse, and significantly
      more likely to score > or = 8 on the SAAST. The SAAST could be completed by the
      majority of acutely ill psychiatric patients even at admission, and was
      clinically useful in the diagnosis of alcohol abuse, especially when used in
      conjunction with the clinical interview.

PMID- 8292642
TI  - Managing tobacco dependence in chemical dependency treatment facilities: a survey
      of current attitudes and policies.
AB  - This paper presents survey results of Minnesota licensed chemical dependency
      treatment facility directors. The baseline survey was conducted by telephone in
      May and June of 1988; and the self-administered follow-up survey was conducted in
      February and March of 1990, subsequent to a statewide tobacco dependence
      educational campaign which targeted Minnesota's chemical dependency
      professionals. Both the baseline (n = 227) and the follow-up (n = 257) surveys
      contained items concerning the directors' beliefs about the health effects of
      tobacco use, their attitudes regarding tobacco use in chemical dependency
      treatment, current tobacco policy in the facility, and barriers to banning
      tobacco use in the facility. The study used a matched-pair analysis (n = 104) of
      the survey data to assess changes in attitudes and practices during the two years
      of the study. The majority (71%) of chemical dependency directors at follow-up
      agree that tobacco dependence should be treated like other drug dependencies. The
      percentage of matched facilities that treat tobacco dependence increased from 10%
      at baseline to 18% at follow-up. The percentage of facilities that prohibit
      smoking increased from 11% at baseline to 27% at follow-up. Implications of the
      findings and areas for further research are discussed.

PMID- 8292643
TI  - Displaying radiologic images on personal computers: image storage and
      compression: Part 1.
AB  - This is the third article of our series for radiologists and imaging scientists
      on displaying, manipulating, and analyzing radiologic images on personal
      computers. Part 1 of this article discusses image storage and reviews the basic
      concepts of information theory and image compression; part 2 will discuss
      specific methods of image compression. There are a wide variety of removable
      storage devices available to users who need to archive radiologic images on their
      personal computers. Tape drives have potentially very large storage capacity but
      slow performance. Removable SyQuest (SyQuest Technology, Femont, CA) and
      Bernoulli disks have near hard disk performance and can store from 100 to 150
      Mbytes. Magneto-optical drives can store nearly 1 Gb on a 5.25" disk, with
      somewhat slower performance. Selecting the most appropriate storage solution
      requires a careful balance of the user's requirements, including performance,
      storage needs, cost and compatibility with other users. Despite the advances in
      low cost high capacity storage technology, image compression remains a crucial
      technology for modern diagnostic radiology because digital images require such
      large amounts of storage. Image compression is possible because radiologic images
      have relatively low entropy (high information content) compared with random
      noise. Image compression is classified as lossless (nondestructive) or lossy
      (destructive). Lossless image compression commonly achieve compression ratios of
      1.5:1 to 3:1 (33% to 67%), whereas lossy compression can compresses images from
      3:1 to 30:1 (67% to 97%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292644
TI  - Increased single-photon emission computed tomography image processing speed
      achieved in personal computers with memory-intensive algorithms.
AB  - Recent dramatic reductions in the cost of computer random access memory (RAM) and
      the ability of newer microprocessors and associated personal computer operating
      systems to address large amounts of memory make novel strategies for high-speed
      image processing possible. We developed image processing algorithms that use this
      newly available memory to achieve increases in effective processing speed. These
      algorithms rely on the use of precomputed lookup tables to avoid repeated use of
      relatively expensive machine instructions, such as multiplications and divisions.
      Programs using this strategy to perform single photon emission computer
      tomography (SPECT) analysis were written in C and assembly language and tested on
      a Macintosh Quadra 950 (Apple Computer, Cupertino, CA) having 64 megabytes of
      RAM. The measured processing times are competitive with most dedicated nuclear
      medicine computers. A general implementation of such programs will allow personal
      computers to compete with dedicated imaging systems, at a substantial reduction
      in cost.

PMID- 8292645
TI  - Imaging transforms for visualizing surfaces and volumes.
AB  - Three-dimensional (3D) visualization in biomedical and other imaging areas is a
      rapidly emerging discipline. The major developments in this field are described
      in a unified and concise way. To this end, we introduce an operator notation to
      describe the basic imaging transforms commonly used in 3D visualization and to
      identify a comprehensive set of basic transforms. We also introduce several new
      basic transforms for filtering and interpolating scenes and structures and for
      rendering surfaces and volumes. We demonstrate not only how the existing
      visualization methodologies can be described concisely, but we also show how a
      great variety of new methodologies can be generated using both the existing
      imaging transforms and the new transforms introduced in this paper. A
      comprehensive evaluation method to compare objectively rendering methods used in
      visualization based on task-specific mathematical phantoms is described. We
      examine in detail separate transform sequences that are best suited for rendering
      robust and frail structures (ie, structures with well- and poorly defined
      boundaries).

PMID- 8292646
TI  - Educational Technology Network: a computer conferencing system dedicated to
      applications of computers in radiology practice, research, and education.
AB  - Educational Technology Network (ET Net) is a free, easy to use, on-line computer
      conferencing system organized and funded by the National Library of Medicine that
      is accessible via the SprintNet (SprintNet, Reston, VA) and Internet (Merit, Ann
      Arbor, MI) computer networks. It is dedicated to helping bring together, in a
      single continuously running electronic forum, developers and users of computer
      applications in the health sciences, including radiology. ET Net uses the Caucus
      computer conferencing software (Camber-Roth, Troy, NY) running on a
      microcomputer. This microcomputer is located in the National Library of
      Medicine's Lister Hill National Center for Biomedical Communications and is
      directly connected to the SprintNet and the Internet networks. The advanced
      computer conferencing software of ET Net allows individuals who are separated in
      space and time to unite electronically to participate, at any time, in
      interactive discussions on applications of computers in radiology. A computer
      conferencing system such as ET Net allows radiologists to maintain contact with
      colleagues on a regular basis when they are not physically together. Topics of
      discussion on ET Net encompass all applications of computers in radiological
      practice, research, and education. ET Net has been in successful operation for 3
      years and has a promising future aiding radiologists in the exchange of
      information pertaining to applications of computers in radiology.

PMID- 8292647
TI  - [Isolation of site-specific endonucleases and methylases from Bacillus cereus
      83].
AB  - The site-specific endonuclease R Bce83I and methylase M Bce83I were isolated from
      Bacillus cereus 83 by three consecutive chromatographies on blue agarose,
      hydroxyapatite and heparin-Sepharose. R Bce83I recognizes [formula: see text]
      sequences on the DNA and cleaves the DNA as indicated by the arrows. The
      endonuclease is stimulated by S-adenosyl-L-methionine and may consequently be
      referred to type IV restriction enzymes.

PMID- 8292648
TI  - [Isocitrate dehydrogenases: forms, localization, properties, and regulation].
AB  - The literary and original data concerning the localization, properties, activity
      regulation and physiological role of NAD- and NADP-dependent isocitrate
      dehydrogenases are reviewed. Possible mechanisms of regulation of anabolic and
      catabolic cellular processes at the isocitrate dehydrogenase level are discussed.
      The data on the structure and chemical modification of the active center
      functional groups suggest that isocitrate dehydrogenases isolated from various
      sources differ in their catalytic properties. The pathways and prospectives in
      practical application of the enzymes are considered.

PMID- 8292649
TI  - [The role of phospholipids and their fatty acids in the structural organization
      of membranes of plasmid-containing and plasmid-less Salmonella derby cells].
AB  - The effect of R-plasmid on the qualitative and quantitative compositions of
      phospholipids and their fatty acids in bacterial (S. derby) cells has been
      studied. It has been found that the lack of R-plasmid in bacterial cells leads to
      a sharp decrease in the phospholipid content, in the phosphatidylcholine content
      in particular, and causes an increase in the per cent content of
      lysophosphatidylcholines. The per cent content of saturated and nonsaturated
      fatty acids of phospholipids in plasmid-free cells does not change appreciably.
      In the plasmid-free strain of S. derby the intensity of lipid peroxidation is
      associated with a relatively high content of alpha-tocopherol.

PMID- 8292650
TI  - [An effective single-stage method of obtaining elastase and cathepsin G from
      human leukocytes].
AB  - A procedure for one-step rapid isolation of highly purified elastase and
      cathepsin G from human leucocytes including biospecific chromatography on Gordox
      Sepharose is described. Electrophoresis in gradient (10-15%) polyacrylamide gel
      in the presence of sodium dodecyl sulfate revealed three elastase isoforms with
      molecular masses of 26.3, 27.8 and 28.9 kDa. Cathepsin G produced one protein
      band with a 27 kDa mobility. The pH optimum for elastase and cathepsin G are 7.0
      7.5 and 7.5-8.0, respectively. The specific activities of elastase and cathepsin
      G preparations as measured by the p-nitrophenyl ester-tert butoxycarbonyl-L
      alanine and the ethyl ester-benzoyl tyrosine, hydrolysis are equal to 3-8 and 20
      40 mumol/min/mg protein, respectively.

PMID- 8292651
TI  - [Biosynthesis of two molecular forms of ceruloplasmin in rat liver and their
      polar secretion into the blood stream and bile].
AB  - Biosynthesis and secretion of ceruloplasmin (CP) in rat liver has been studied in
      order to elucidate its role in the distribution, transport and excretion of
      copper in the body. The kinetics and topography of CP synthesis, intracellular
      transport and secretion were followed using in vivo pulse-chase experiments. It
      was found that the newly formed CP was firmly bound to endoplasmic reticulum
      membranes in the hepatocytes. Liver slices incubated in vitro with
      [35S]methionine were characterized by a two-stage release of [35S]CP into the
      medium. After 30-min incubation the medium contained 200 kDa CP-like protein,
      while after 120 min the secretion of 130 kDa CP was demonstrated. The pulse
      labelling experiments with [35S]methionine in rats with catheters inserted into
      the carotid artery and the common bile duct revealed the polar secretion of two
      distinct CP species differing in molecular structure and secretion rate. The
      slowly secreted CP isoform is the authentic serum CP, while the rapidly secreted
      CP is the specific biliary CP. The physiological function of biliary CP and its
      role in the pathogenesis of Wilson's disease are discussed.

PMID- 8292652
TI  - [Alkaline extracellular proteinase from Bacillus intermedius. Isolation,
      purification, and some properties of the enzyme].
AB  - Extracellular alkaline proteinase was isolated from the Bacillus intermedius
      culture medium. The enzyme was purified by ion-exchange chromatography 200-fold
      to apparent homogeneity and has a specific activity of 950 u./mg. The proteinase
      was maximally active at pH 10, 50 degrees C and is stable at pH 6.3-11.0. EDTA, o
      phenanthroline or p-chloromercuribenzoate did not affect the enzyme activity,
      while phenylmethylsulfonyl fluoride inhibited it by 95-97%. It was concluded that
      the enzyme is subtilisin-like and belongs to the serine proteinase family of
      Bacilli.

PMID- 8292653
TI  - [Structure-functional properties of conjugates of proteins with polyalkylene
      oxides: study by a fluorescence method].
AB  - A fluorescent study of some structural and functional properties of conjugates of
      a number of proteins (bovine serum albumin, pyruvate kinase, alpha-chymotrypsin,
      and the two toxic proteins of plant origin--ricin and viscumin) with polyalkylene
      oxides (polyethylene glycol and pluronic) has been carried out. Analysis of the
      intrinsic protein fluorescence showed that the structure and stability of various
      protein conjugates to denaturing agents change only slightly: the conformational
      mobility of tryptophan residues accessible to the solvent decreases, whereas that
      of tryptophan residues localized in the protein regions of low polarity remains
      unchanged. Besides, the conjugates display a higher thermal stability in
      comparison with their native proteins. The fluorescence of 1-anilinonaphthalene-8
      sulfonic acid and water insoluble 2',3',4',5'-tetrabenzoylriboflavin bound to the
      native and modified proteins indicated that modification of the proteins with
      polyalkylene oxides decreased the polarity and increased the viscosity of the
      microenvironment. Hence, this modification makes it possible to change some
      functional characteristics of the protein without causing any significant changes
      in its structure.

PMID- 8292654
TI  - [Change in the size of particles in actomyosin suspensions during
      superprecipitation].
AB  - Changes in the properties of natural actomyosin suspensions, such as turbidity,
      light scattering, volume concentration, particle size and particle size
      distribution during superprecipitation (SPP) of actomyosin in media of different
      compositions have been investigated. Two sets of changes indicating the existence
      of two SPP types--the "immediate" SPP characterized by a rapid one-step rise in
      turbidity and the "spontaneous" SPP, when the slow increase in turbidity follows
      the clear phase, have been revealed. In both cases the mechanism of the increase
      in the suspension turbidity is assumed to be similar and is conditioned by an
      increase in the refraction index (density) of the particles; however, the ways of
      formation of dense particles are different. During the "immediate" SPP, the
      particle density increases due to particle striction, whereas during the
      "spontaneous" SPP dense particles are formed as a result of ordered lateral
      association of myosin and actin filaments.

PMID- 8292655
TI  - [Inactivation of naloxone binding with opioid receptors in rat brain membranes].
AB  - Inactivation of naloxone binding to rat brain membrane-bound mu-opioid receptors
      (37 degrees C) was studied using the radioligand method. The rate inactivation
      constant (k(in) = 5.2 +/- 1.0 x 10(-3) min-1), the activation energy (Ea = 82.5
      kJ/mol) and the change in the activation entropy (delta S = -14 kJ/K.mol) were
      determined. Incubation with unsaturated fatty acids (linoleic and arachidonic
      acids, 10(-7)-10(-4) M), cardiolipin (10(-5)-10(-4) M), phosphatidylinositol (10(
      5)-10(-4) M), 2.6-ditretbutyl-4-exitoluene (10(-4) M), and argon produced a
      significant stabilizing effect on naloxone binding. The microviscosity changes in
      the ESR probe (2,2,6,6-tetramethyl-4-capryloyloxypiperidine-1-oxyl) environment
      and peroxidase oxidation of membrane lipids during incubation of rat brain
      membranes were investigated. It was suggested that the main reason for the
      decrease in the opioid receptor activity is the peroxidation of unsaturated acid
      lipids in the specific receptor environment and the reduction of the lipid
      viscosity.

PMID- 8292656
TI  - Enhancement of antigenic site detection with gold labeled secondary and tertiary
      antibodies using the immunogold-silver staining method.
AB  - We report a modification of the immunogold-silver staining method (IGSS) for
      localizing hepatic phosphoenolpyruvate carboxykinase (PEPCK) in tissue sections,
      and we compare the efficacy of localizing the primary antibody with either a 5 nm
      gold labeled secondary antibody or 5 nm gold labeled secondary and tertiary
      antibodies. Light microscope examination of 10 microns frozen sections
      demonstrated that the use of combined secondary and tertiary gold labeled
      antibodies was superior to using a secondary gold labeled antibody alone. The
      increased labeling density (number of colloidal gold particles/antigenic
      site/cell) achieved by combined gold labeled antibodies was confirmed by electron
      microscopy. The increased labeling density resulted in a two-thirds reduction in
      the time needed for the IGSS physical development of the silver shells and less
      background. We achieved intense specific staining of hepatocytes expressing PEPCK
      while minimizing background staining. The use of combined secondary and tertiary
      gold labeled antibodies enhances the signal-to-noise ratio, achieves high
      resolution and is a suitable method for use in both light and electron
      microscopy.

PMID- 8292657
TI  - A study of structure and degradation of nonpolymeric biomaterials implanted in
      bone using reflected and transmitted light microscopy.
AB  - Orthopedic biomaterials currently are made of metal alloy coated with one or more
      thin layers of dense or porous ceramic or metal. Sections of these materials
      implanted in human bone were made without altering the implant or bone-implant
      interfaces. Bone containing an implant was fixed and then embedded in
      polymethylmethacrylate. Thick sections were made using a cooled, low speed
      diamond saw, then ground and polished. Some were stained by fuchsin-toluidine
      staining solution, others were acid etched to reveal the structure of the metal
      contained in the prosthesis. Observation by reflected and transmitted light
      microscopy revealed microstructure of the implant material as well as features of
      the surrounding tissues.

PMID- 8292658
TI  - Measurement of cutaneous microvascular exudates using Evans blue.
AB  - As an approach to the study of inflammation, strategies were evaluated for
      quantitative assessment of plasma exudate from the cutaneous microvasculature.
      Measurements were based on recovery of Evans blue dye (EB) from rat skin. After
      preliminary studies to evaluate extraction methods, almost complete EB recovery
      was accomplished by homogenizing tissue in a mixture of acetone, water and sodium
      sulfate. When sources of potential variation were identified, expression of
      results as agonist-induced plasma accumulation provided precise results based on
      EB measurements. Also, the feasibility of parallel biochemical studies was
      demonstrated.

PMID- 8292659
TI  - Embedding of neural tissue in agarose or glyoxyl agarose for vibratome
      sectioning.
AB  - Agarose was used to embed the brain or spinal cord of lampreys or rats before
      cutting vibratome sections. Agarose embedding was compatible with
      immunocytochemistry or the use of horseradish peroxidase as a neuroanatomical
      tracer. Concentrated agarose with high intrinsic gel strength was optimal for
      embedding glutaraldehyde fixed neural tissue. A quick procedure was to blot
      tissue and embed in 5% (w/v) Sigma type I-A or Litex type LSL agarose at 45-55 C
      dissolved in 50 mM neutral-pH TRIS buffer before cutting 50-100 microns vibratome
      sections. An alternative procedure that improved retention of tissue sections in
      the agarose was to rinse the tissue in H2O, blot and embed in 5% (w/v) Sigma type
      I-A or Litex type LSL agarose at 45-55 C dissolved in H2O, then equilibrate the
      block overnight in buffer. Phosphate buffer prevented complete dissolving of
      agarose. Tissue could be covalently linked to the embedding matrix using a novel
      aldehyde-derived agarose (NuFix, FMC BioProducts). Slices of spinal cord from
      neonatal rats could be cut after embedding in 5% FMC SeaPrep agarose in rat
      Ringer's at 23-26 C.

PMID- 8292660
TI  - Intrathecal synthesis of beta 2-microglobulin and lysozyme: differential markers
      of nervous system involvement in patients infected with human immunodeficiency
      virus type 1.
AB  - beta 2-Microglobulin and lysozyme were determined in paired serum and
      cerebrospinal fluid samples from 137 patients, using immunofluorometry and ELISA,
      respectively. Of these patients, 54 were infected by human immunodeficiency virus
      type 1 (HIV1) (including 20 AIDS dementia patients), 73 were HIV1-seronegative
      with neurological diseases (meningitis (n = 10), multiple sclerosis (n = 29),
      other neurological diseases (n = 34)) and 10 were controls. Intrathecal synthesis
      of beta 2-microglobulin occurred in each group. Conversely, lysozyme intrathecal
      synthesis was found only in meningitis (10/10) and in HIV1-infection (24/54). A
      pathological increase in beta 2-microglobulin intrathecal synthesis (> or = 2
      mg/l) was observed in 45 patients (34 HIV1-infected patients and 11 HIV1
      seronegative patients with neurological diseases). Serum concentration and
      intrathecal synthesis of beta 2-microglobulin were correlated only in the 20 AIDS
      dementia patients. The cerebrospinal fluid beta 2-microglobulin and lysozyme
      concentrations were correlated in the 54 HIV1-infected patients only. Blood CD4 +
      T-cell count was correlated negatively with beta 2-microglobulin intrathecal
      synthesis but not with lysozyme intrathecal synthesis. These data suggest that in
      the absence of any central nervous system opportunistic process the increase of
      beta 2-microglobulin intrathecal synthesis (> or = 2 mg/l) may be a reliable
      marker of central nervous system involvement in HIV1-infected patients.
      Intrathecal synthesis of lysozyme was related principally to HIV1-encephalitis
      and central nervous system opportunistic processes.

PMID- 8292661
TI  - Composition of urinary coproporphyrin isomers I-IV in human porphyrias.
AB  - The urinary distribution and relative proportions of the four coproporphyrin
      isomers I-IV were investigated in 50 patients suffering from hepatic and
      erythropoietic types of hereditary porphyrias. A highly efficient sample
      preparation method was applied to isolate urinary coproporphyrins, the isomer
      ratios of which were quantitated by isocratic ion-pair high-performance liquid
      chromatography. Results showed a significant decrease (p < 0.001) of the
      proportion of coproporphyrin I in acute hepatic porphyria (acute intermittent
      porphyria, hereditary coproporphyria, variegate porphyria, porphobilinogen
      synthase deficiency porphyria) as compared with chronic hepatic porphyria
      (porphyria cutanea tarda, chronic hepatic porphyria type B and C) (13.2 +/- 5.3%,
      mean +/- S.D., vs. 31.4 +/- 11.5%). Conversely, the proportion of isomer III was
      significantly higher (p < 0.001) in acute hepatic porphyria than in chronic
      hepatic porphyria (80.9 +/- 5.2% vs. 62.2 +/- 10.9%). As expected, the highest
      level of coproporphyrin I (90.0 +/- 1.9%) was found in congenital erythropoietic
      porphyria. The atypical coproporphyrins II and IV were detected in all types of
      porphyria analysed and ranged from 0.2 to 9.0%; no significant differences were
      seen between acute and chronic hepatic porphyrias. The diagnostic importance of
      the isomer ratios of coproporphyrins I and III has been confirmed in our study,
      while the significance of the atypical coproporphyrin isomers II and IV is still
      unclear at present.

PMID- 8292662
TI  - A trypsin sensitive stromelysin isolated from rheumatoid synovial fluid is an
      activator for matrix metalloproteinases.
AB  - The processing of synovial fluids of patients suffering from rheumatoid arthritis
      led to the characterization of a neutral metalloproteinase with polymorphonuclear
      leukocyte progelatinase and polymorphonuclear leukocyte procollagenase activating
      properties. The activator exhibits a relative molecular mass of M(r) 27,000 and
      is an active form of stromelysin. Thus, it reacts specifically with antibodies
      raised against human stromelysin, splits polymorphonuclear leukocyte
      progelatinase in a manner characteristic of stromelysin, and is inhibited by EDTA
      as well as by a tissue inhibitor of metalloproteinases (TIMP-2). The activator
      shows a high specificity for the matrix metalloproteinases, polymorphonuclear
      leukocyte progelatinase and polymorphonuclear leukocyte procollagenase. It shows
      only weak hydrolysis of casein and gelatin, and it does not activate fibroblast
      M(r) 72,000 progelatinase. Brief treatment with trypsin does not lead to a
      significant change in the activator's relative molecular mass, but induces a
      rapid loss of its activating activity for polymorphonuclear leukocyte
      progelatinase, while its proteolytic activity against the synthetic substrate, N
      (2,4)-dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg, is increased about 3-fold.
      The same tryptic treatment does not affect the activator's proteolytic activity
      towards casein and gelatin.

PMID- 8292663
TI  - Serum lipoprotein pattern in rats, dogs and monkeys, including method comparison
      and influence of menstrual cycle in monkeys.
AB  - The serum lipoprotein pattern (HDL-, LDL- and VLDL-cholesterol) was determined in
      normal untreated rats, dogs and monkeys using the density gradient centrifugation
      method, and compared with that in humans. The serum of rats (Wistar) and dogs
      (Beagle) was found to contain mainly HDL-cholesterol, whereas the serum of
      monkeys (Macaca fascicularis) consists of similar amounts of HDL-cholesterol and
      LDL-cholesterol, as in humans. In contrast to rats and dogs, monkeys showed a
      very low amount of serum VLDL-cholesterol. Comparison of four different methods
      (density gradient centrifugation, FPLC, agarose gel electrophoresis and
      precipitation methods) for determination of HDL- and LDL-cholesterol in monkey
      serum showed that density gradient centrifugation and FPLC-methods have the
      highest accuracy and recovery rate. The FPLC-method offers the extra advantages
      that it requires less sample volume and is less laborious. In a separate
      experiment, the influence of the menstrual cycle on the serum lipoprotein pattern
      was investigated in female monkeys. No changes in total cholesterol, HDL- or LDL
      cholesterol were detected in serum samples obtained in the follicular and luteal
      phases of the cycle. In conclusion, monkeys (Macaca fascicularis) may be more
      suitable than rats or dogs for the comparison of the effect of different
      compounds on serum lipoproteins in pharmacological and toxicological studies,
      because the lipoprotein pattern in this species is similar to that of humans.

PMID- 8292664
TI  - Fourier transform infrared spectroscopy measures 1H/2H ratios of native water
      with a precision comparable to that of isotope ratio mass spectrometry.
AB  - A fast and easy method is described which uses Fourier transform infrared
      spectroscopy (FT-IR) to measure the 1H/2H ratio of aqueous samples of less than
      100 microliters with high precision (+/- 0.2-0.5% in the range of 89 to 2680
      microliters/l). Using a thermostat-controlled CaF2 cell, low resolution
      absorption specta (8 cm-1) are measured. The integral of absorption in the range
      of 2600 and 2460 cm-1 (O2H vibration) is used to analyse the 2H content of the
      sample. For measurements at low enrichment five standards are used (SLAP: 89.00
      microliters/l, GISP: 126.3 microliters/l, V-SMOW: 156.0 microliters/l, all from
      the International Atomic Energy Agency, Vienna, Austria, standard 1: 183.3
      microliters/l, standard 2: 222.5 microliters/l, both prepared by weighing and
      controlled by isotope ratio mass spectrometry (IR-MS)). For measurements at high
      enrichment three standards are used (standard 2: 222.5 microliters/l, standard 3:
      1323 microliters/l, standard 4: 2680 microliters/l, all prepared by weighing and
      controlled by IR-MS). Measured and reported 2H concentrations coincide very well,
      two samples for quality control (145 and 1612 microliters/l) were measured with a
      precision of 0.3 and 0.4% corresponding to +/- 0.5 and 5.9 microliters/l.

PMID- 8292665
TI  - Postmenopausal hormone replacement therapy with Tibolone decreases serum
      lipoprotein(a).
AB  - Lipoprotein(a) is a cholesterol-rich plasma lipoprotein consisting of LDL and
      apolipoprotein(a). Apolipoprotein(a) shows structural similarity with plasminogen
      and thus may interfere with thrombogenesis. Lipoprotein(a) has been shown to be a
      strong independent risk factor for coronary heart disease. So far no drug or diet
      is known to have prominent effects on the serum levels of lipoprotein(a). In the
      present study we found a highly significant decrease (in the order of 26%) of
      lipoprotein(a) in 28 women treated for 6 months with Tibolone, compared with an
      age-matched healthy control group. Tibolone is a synthetic steroid with
      gestagenic and weak androgenic and oestrogenic properties, which shows no
      stimulation of the endometrium. Tibolone also produced a decrease in HDL
      cholesterol of 23% (p < 0.001), a decrease in apolipoprotein A-I of 14% (p <
      0.001) and an increase in apolipoprotein B of 17% (p < 0.001), whereas the
      control group showed no significant changes in these quantities. Tibolone in a
      daily dose of 2.5 mg is at present the only complete postmenopausal hormone
      replacement therapy that shows a significant inhibiting influence on serum levels
      of lipoprotein(a). Its effect on lipoprotein(a) might counterbalance, at least to
      some extent, the theoretical adverse effect on the other lipoprotein risk
      factors.

PMID- 8292666
TI  - Granulocyte chemotaxis measured in a Boyden chamber assay by quantification of
      neutrophil elastase.
AB  - The human polymorphonuclear leukocyte reaction in response to chemotactic or
      chemokinetic stimulation is often assayed using the Boyden chamber technique. We
      present a quick and reliable method for evaluating Boyden chamber experiments,
      which avoids time-consuming cell counting and does not require expensive
      equipment. This method is based on assaying human neutrophil elastase, a serine
      protease derived from polymorphonuclear leukocytes. We tested the method in
      different types of Boyden chambers equipped with two superimposed filters or a
      filter amnion membrane combination. The chambers were incubated with the cells
      for 2 h then dismantled and the elastase activity in supernatant, filters or
      membrane was assayed. The results were compared with the results obtained by cell
      counting, or measured by determination of myeloperoxidase. There was a good
      correlation between the cell count and elastase technique (r = 0.90), but the
      elastase method achieved higher intra- and interassay precision. Myeloperoxidase
      and elastase results also correlated well (r = 0.94) and showed comparable intra-
      and inter-assay precision. With the elastase method it was also possible to
      quantify polymorphonuclear leukocyte reactions on an amnion membrane surface. In
      amnion membrane assays the percentage of cells which reacted in response to
      formyl-peptide stimulation was not altered by varied cell concentrations, and
      polymorphonuclear leukocytes showed little unstimulated adherence or migration.

PMID- 8292667
TI  - Immunological and functional properties of the acetylcholine receptor expressed
      on the human cell line TE671.
AB  - In the first part of the present study we compared the antigenicity of affinity
      purified acetylcholine receptors from the cell line TE671 and from human skeletal
      muscle. The reactivities of the two acetylcholine receptor preparations showed a
      strong correlation (r = 0.96) in a radioimmunoassay using sera from myasthenia
      gravis patients. In additional functional studies, carbamylcholine stimulated
      cAMP production in TE671 cells to 130%. This increase was even more pronounced
      when TE671 cells were grown in the presence of dexamethasone. alpha-Bungarotoxin
      completely blocked this carbamylcholine-induced cAMP increase. Using the Ca2+
      indicator, indo-1, it was shown that intracellular Ca2+ concentrations ([Ca2+]i)
      were elevated in TE671 cells after stimulation with carbamylcholine. This effect
      was also completely blocked by alpha-bungarotoxin. To test the functional
      activity of autoantibodies against the acetylcholine receptor, TE671 cells were
      preincubated with sera from myasthenia gravis patients. In one third of sera a
      significant inhibition of the agonist-stimulated [Ca2+]i increase was detected,
      possibly caused by antibodies directed to functionally important areas of the
      acetylcholine receptor. There was no correlation between the inhibition rate of
      [Ca2+]i and anti-acetylcholine receptor antibody titres in these patient sera.

PMID- 8292668
TI  - Mechanism of action of methotrexate: experimental evidence that methotrexate
      blocks the binding of interleukin 1 beta to the interleukin 1 receptor on target
      cells.
AB  - Interleukin 1, a multifunctional cytokine, plays a central role in inflammatory
      processes and induction of the immune response. Target cells possess 200-5000 (or
      more) interleukin 1 receptors per cell, but they exhibit a full biological
      response when only 1-2% of these receptors are occupied by interleukin 1 alpha or
      1 beta. Methotrexate has been reported to be beneficial in several inflammatory
      and autoimmune diseases. On the other hand, many of these diseases are known to
      share an overproduction of interleukin 1. It has been demonstrated that
      methotrexate has no influence on the interleukin 1 synthesis, so we focused our
      attention on the ability of methotrexate to interfere with the binding of
      interleukin 1 beta to the interleukin 1 receptor. The experiments were performed
      on monocytes, lymphocytes and granulocytes using a recombinant human cytokine
      probe. Methotrexate led to an astonishing decrease in the binding of interleukin
      1 beta to the interleukin 1 receptor of peripheral blood cells, whereas
      methylprednisolone and indomethacin were not inhibitory. The inhibitory effect of
      methotrexate was dose dependent. An excess of interleukin 1 beta abolished the
      inhibition of cytokine binding by methotrexate. We also demonstrated that
      methotrexate does not affect the integrity of the interleukin 1 receptor or of
      the target cells. Our results demonstrate that methotrexate blocks the
      interleukin 1 beta-interleukin 1 receptor pathway. Methotrexate is therefore
      another interleukin 1 inhibitor and a clinically efficient anticytokine.

PMID- 8292669
TI  - The molecular basis of hereditary fructose intolerance in Italian children.
AB  - We investigated the molecular defects of the aldolase B gene in five unrelated
      patients affected by hereditary fructose intolerance. The techniques used were
      DNA amplification, direct sequencing and allele-specific oligonucleotide (ASO)
      hybridization. The most frequent substitutions found in the hereditary fructose
      intolerance alleles analysed were the A174D and the A149P mutations, which
      account for 50% and 30% of the alleles, respectively. In two unrelated families,
      we found a rare mutation, the MD delta 4 previously described only in one British
      family, which may be an important cause of the disease in Italy.

PMID- 8292670
TI  - Enhanced production of calcitriol, and hypercalcaemia in a patient with
      sarcoidosis provoked by daily intake of calciol.
AB  - A case of sarcoidosis is described which presented with hypercalcaemia and renal
      insufficiency. Initially, a calciol intoxication was diagnosed, because a high
      daily intake was suspected. However, vitamin D3 metabolites in the blood revealed
      normal concentrations of calcidiol, but extremely high concentrations of
      calcitriol. These features rejected the first diagnosis and pointed to high
      endogenous calcitriol production, which may take place in granulomatous diseases.
      This is caused by an increased 1-alpha-hydroxylation reaction in activated
      macrophages. Eventually, muscle biopsy revealed non-caseating granulomas,
      confirming the diagnosis of sarcoidosis.

PMID- 8292671
TI  - Comparison of the automated random access immunoassay analysers, ACS-180 (Ciba
      Corning) and AIA-1200 (Tosoh).
AB  - Two random access immunoassay analysers, the ACS-180 (Ciba Corning) and the AIA
      1200 (Tosoh Corp.) were compared with respect to performance and user
      friendliness. Precision studies revealed an almost equal intra-assay variation
      coefficient, but day-to-day reproducibility was better on the AIA-1200. Recovery
      of dilution series of tumour markers was too high with the ACS-180. Both systems
      were free from carry-over effects, on account of the extra wash step in the ACS
      180 (for thyrotropin, carcinoembryonic antigen and human chorionic gonadotropin)
      and the separate pipetting tip in the AIA-1200. Reagent stability is better in
      the AIA-1200 than in the ACS-180. The AIA-1200 is more user-friendly and produces
      a higher throughput than the ACS-180 in daily routine operation (92 results/hour
      vs. 78 results/hour).

PMID- 8292672
TI  - Pain perception threshold in major depression.
AB  - Somatosensory perception threshold (SPT) and pain perception threshold (PPT) were
      studied in 16 patients with major depression, compared to the findings in an age
      matched and gender-matched control group and related to the psychopathological
      state evaluated by means of the Hamilton Depression Scale. Perception thresholds
      were assessed by means of a noninvasive high-frequency electric skin stimulation.
      Absolute perception thresholds were increased in the patients. However, the
      relative pain perception threshold (RPPT = PPT: SPT) was significantly reduced.
      RPPT was positively correlated with retardation. It was negatively correlated
      with anxiety, suggesting that a reduction of pain perception thresholds in
      depressive patients may be attributed to anxiety and impaired stress-coping.

PMID- 8292673
TI  - Relationships between increased haptoglobin plasma levels and activation of cell
      mediated immunity in depression.
AB  - Recently, it was found that major depression is accompanied by an acute phase
      (AP) response with increased haptoglobin (Hp) plasma levels and various indices
      of systemic immune stimulation. The present study has been carried out in order
      to determine the relationships between hyperhaptoglobinemia and indices of
      systemic immune activation in severe depression. Toward this end, the authors
      investigated the relationships between Hp levels and number of leukocytes,
      monocytes, neutrophils, lymphocytes, and activated T lymphocytes (CD25+, HLA
      DR+), in depression. Hp plasma levels were significantly higher in major
      depressed subjects as compared to healthy controls and minor depressives. There
      was a significant positive correlation between Hp levels and severity of illness.
      Hp plasma levels showed significant and positive relationships with the absolute
      number of leukocytes, neutrophils, monocytes, CD25+ and HLA-DR+ T cells. Up to
      35% of the variance in Hp levels could be explained by the regression on the
      number of neutrophils and HLA-DR+ T cells. The results show that
      hyperhaptoglobinemia in major depression is significantly related to activation
      of cell-mediated immunity.

PMID- 8292674
TI  - Improvement in cognitive functions and psychiatric symptoms in treatment
      refractory schizophrenic patients receiving clozapine.
AB  - Cognitive functions and psychopathology were assessed in 36 treatment-refractory
      schizophrenic patients before initiation of clozapine, and at 6 weeks and 6
      months, thereafter. Before treatment, cognitive impairment was found in each
      measure of memory, attention, and executive function as compared with 26 normal
      controls. After both 6 weeks and 6 months of treatment, significant improvement
      occurred in the Controlled Oral Word Association Test, a measure of retrieval
      from reference memory. Improvement was also noted at 6 months in the Category
      Instance Generation Test, another measure of retrieval from reference memory, and
      in some, but not all, tests of executive function, attention, and recall memory.
      Clozapine treatment also resulted in significant improvement in Brief Psychiatric
      Rating Scale (BPRS) Total and Positive symptom scores at both 6-week and 6-month
      assessment points. There was some evidence for a relationship between improvement
      in psychopathology and cognitive function. The improvement in cognitive function
      during clozapine treatment could have consequences for capacity to work and
      social function.

PMID- 8292675
TI  - APP mutations and schizophrenia.

PMID- 8292676
TI  - Neopterin and biopterin CSF levels in tardive dyskinesia after clozapine
      treatment.

PMID- 8292677
TI  - The Wernicke-Kleist-Leonhard school of psychiatry.

PMID- 8292678
TI  - The effects of fenfluramine on sleep and prolactin in depressed inpatients: a
      comparison of potential indices of brain serotonergic responsivity.
AB  - The effects of fenfluramine, an indirect serotonergic agonist, on
      electroencephalographic sleep and prolactin secretion were assessed in 12
      unmedicated inpatients with a primary diagnosis of major depressive episode.
      Compared to prefenfluramine profiles, sleep studies performed following
      fenfluramine administration showed a statistically significant reduction of slow
      wave sleep (SWS) (p < 0.001) and a corresponding increase in percentage of stage
      2 sleep (p < 0.007). Automated delta wave counts per min decreased significantly
      during the first nonrapid eye movement (NREM) period (p = 0.04), and automated
      rapid-eye movement (REM) counts were also decreased in the second REM period (p =
      0.02). These effects on sleep electroencephalogram (EEG) did not correlate
      significantly with another measure of serotonergic responsivity, namely peak
      prolactin level following fenfluramine, nor with the severity of depression. The
      reductions in SWS and REM counts are proposed to be the result of time-dependent
      changes in serotonergic neurotransmission following the administration of
      fenfluramine. These findings are consistent with earlier work suggesting a role
      for serotonin in initiation and regulation of SWS and REM sleep.

PMID- 8292679
TI  - The effects of ECT stimulus dose and electrode placement on the ictal
      electroencephalogram: an intraindividual crossover study.
AB  - Recent evidence suggests that electroconvulsive therapy (ECT) efficacy depends
      upon both electrode placement and the degree to which stimulus dosage exceeds
      seizure threshold (T), and not simply on surpassing a minimum seizure duration as
      has been assumed. In light of these findings and studies reporting ictal
      electroencephalogram (EEG) differences between bilateral and unilateral ECT, we
      performed this 19-subject intraindividual crossover study of the effects of dose
      and electrode placement on the ictal EEG. We found ictal EEG evidence of greater
      seizure intensity with bilateral than unilateral ECT and with higher dosage (2.25
      T) compared with barely suprathreshold stimuli. Seizure duration was not longer
      with bilateral than unilateral ECT and actually decreased with increased dose. A
      number of ictal EEG variables separated the unilateral 2.25 T and unilateral T
      conditions, which reportedly differ in efficacy, and therefore, these EEG
      measures show promise as markers of treatment adequacy.

PMID- 8292680
TI  - Total nerve cell number in neocortex in chronic schizophrenics and controls
      estimated using optical disectors.
AB  - The total number of neurons was estimated in eight brains from chronic
      schizophrenic men and compared with 16 gender- and age-matched controls. The
      average total neocortical nerve cell number was 22.12.10(9) in schizophrenics and
      22.06.10(9) in controls. The estimate of total cell numbers can not demonstrate
      more subtle neuronal losses of specific cell types or cell loss in specific
      regions, but the result does not indicate that a major cell loss in the neocortex
      of schizophrenics is part of the disease. The sampling scheme was based on a
      uniform sampling design, the counting was performed using new stereological
      principles and the majority of the cerebral cortex was left intact providing the
      possibility for resampling and further analysis.

PMID- 8292681
TI  - Schizophrenia, narcolepsy, and HLA-DR15, DQ6.
AB  - A strong association between HLA-DR2, DQ1 and narcolepsy-cataplexy has been known
      since 1986. In 1990 a subdivision (HLA-DR15, DQ6) was shown to be equally
      associated. Narcolepsy symptoms include rapid eye movement (REM)-sleep intrusion
      hallucinations during the day. Some narcoleptics may be so hallucinated that they
      become delusional and receive a diagnosis of schizophrenia. Fifty-six inpatient
      schizophrenics and 56 normal controls were compared to see if there was an excess
      of the narcolepsy-associated antigens (NAA) among schizophrenics. Patients had
      frequency of the NAA 3.89 times higher than controls. After a subset was studied
      by night (n = 9) and day (n = 7) polysomnography, two patients were found to be
      true narcoleptics. Their psychosis improved with treatment for narcolepsy. When
      NAA(+) and NAA(-) schizophrenics were compared, the NAA(+) subgroup had
      significantly higher Brief Psychiatric Rating Scale (BPRS) scores and more
      hospitalizations. There were no effects attributable only to gender or race. We
      conclude that narcolepsy can simulate schizophrenia in some cases, and that even
      in nonnarcoleptic patients, the HLA-DR15,DQ6 antigens mark a group of severe
      schizophrenics that merits further study.

PMID- 8292682
TI  - Autoradiographic localization of CCK-8 binding sites in the rat brain: effects of
      chronic methamphetamine administration on these sites.
AB  - The effects of chronic methamphetamine (MAP) administration (at a dose of 4 mg/kg
      for 14 days) on [3H]pCCK-8 binding sites in the rat brain were investigated by an
      in vitro quantitative receptor autoradiographic technique. The number of [3H]pCCK
      8 binding sites was significantly reduced in layers III and IV of the medial
      frontal, anterior, and posterior cingulate cortices, in layers II-IV of the
      retrosplenial cortex, in layers III-VI of the dorsal insular cortex, and in the
      reticular nucleus of the thalamus, compared to these numbers in a control group
      of rats that received physiologic saline. Further, chronic methamphetamine
      administration led to a significant increase in the number of these binding sites
      in layer I of the entorhinal cortex. These findings indicate the CCK peptides in
      the limbic lobe may be closely related to the development of the behavioral
      changes associated with methamphetamine sensitization. In addition, these results
      provide supporting evidence for the involvement of the limbic system in the
      pathophysiology of schizophrenia.

PMID- 8292683
TI  - Sleep after spousal bereavement: a study of recovery from stress.
AB  - AIM: In this study, we compared repeated measures of electroencephalographic
      (EEG) sleep and subjective sleep quality in nondepressed, spousally bereaved
      elders and a healthy control group, in order to search for possible
      psychobiological correlates of bereavement not confounded by concurrent major
      depression. METHOD: Laboratory-based EEG sleep studies and measures of subjective
      sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were repeated at 3, 6, 11,
      18, and 23 months after spousal bereavement in a study group of 27 elderly
      volunteers. Data were compared with similar measures from a control group of 27
      nonbereaved subjects recorded on three occasions 1 year apart. Repeated-measures
      analysis of variance (ANOVA), using age as a covariate, examined effects due to
      time on selected variables in the bereaved group, as well as effects due to
      group, time, and group-by-time interactions in the experimental and control
      subjects. RESULTS: Bereaved and control groups showed consistent differences over
      time in the phasic measures of rapid eye movement (REM) sleep (higher in bereaved
      subjects during the first and third REM sleep periods), but were similar on all
      other EEG sleep measures over the 2 years of observation. The bereaved showed a
      small decline in the percentage of slow-wave sleep over 2 years, but measures of
      sleep efficiency, REM latency, and delta sleep ratio were stable and did not
      differ from values seen in control subjects. Bereaved and control subjects were
      also similar on subjective sleep quality. CONCLUSION: During successful
      adaptation to the loss of a spouse, and in the absence of major depression,
      spousal bereavement is associated with elevation in the phasic measures of REM
      sleep but does not appear to be associated with other physiologic sleep changes
      typical of major depression when studied at 3 to 23 months after the event.
      Although this observation does not preclude the possibility of significant sleep
      disturbance nearer the time of the event, it suggests that preservation of normal
      sleep following a major negative life event may be an important correlate of the
      resilience seen in successful aging. The elevation in REM density may provide a
      psychobiological correlate of bereavement not confounded by concurrent major
      depression.

PMID- 8292684
TI  - Individual differences in cerebral metabolic patterns during pharmacotherapy in
      obsessive-compulsive disorder: a multiple regression/discriminant analysis of
      positron emission tomographic data.
AB  - A multiple regression/discriminant analysis of positron emission tomographic
      cerebral metabolic (rCMRglc) data in 10 obsessive-compulsive disorder (OCD)
      patients before and during pharmacotherapy was carried out to see if rCMRglc
      interdependencies distinguished OCD patients from controls. Before therapy, a
      discriminant function reflecting parietal, sensorimotor, and midbrain rCMRglc
      interdependencies correctly classified eight (80%) of the 10 patients as OCD;
      after therapy, six (70%) were classified as controls, most of whom were
      responders. Before therapy, rCMRglc interdependencies involving basal ganglia,
      thalamus, limbic, and sensory and association cortical regions distinguished 67%
      of patients who clinically responded to drug (RESP, n = 6) and 75% of patients
      who did not (NRESP, n = 4) from controls. After therapy, all RESP were classified
      as controls; classification of NRESP remained unchanged. The results suggest the
      conjunctive utility of this method to assess individual differences in rCMRglc
      during pharmacotherapy, and to explore the neurobiology of OCD.

PMID- 8292685
TI  - The Sleep-Wake Activity Inventory: a self-report measure of daytime sleepiness.
AB  - The purpose of this study was to develop a valid multidimensional self-report
      measure of sleepiness. There were 554 subjects who completed the inventory. The
      structure of the Sleep-Wake Activity Inventory (SWAI) was derived from principal
      components analysis. The independent predictive strength of the factors was
      assessed by forward stepwise regression analysis with the average sleep latency
      on the Multiple Sleep Latency Test (MSLT) as the dependent variable. The scores
      on each of the factors were also compared by the level of sleepiness determined
      by the MSLT (pathological, diagnostic gray area, and normal). Factor analysis
      showed the existence of six factors on the SWAI (Excessive Daytime Sleepiness
      [EDS], Psychic Distress, Social Desirability, Energy Level, Ability to Relax and
      Nocturnal Sleep). The EDS factor was the best predictor of average MSLT. It was
      also able to differentiate pathological levels of sleepiness from both the
      diagnostic gray and normal levels of sleepiness. EDS factor scores were sensitive
      to changes in sleep physiology as improved scores followed normalization of sleep
      disordered breathing. The SWAI was shown to be easy to complete, have a multi
      dimensional structure, have a EDS factor useful in the prediction of average MSLT
      scores, be sensitive to differential levels of sleepiness, and change as a result
      of effective treatment.

PMID- 8292686
TI  - The perennial alcohol problem.

PMID- 8292687
TI  - Growth hormone response to intravenous clonidine in social phobia: comparison to
      patients with panic disorder and healthy volunteers.
AB  - The growth hormone (GH) response to intravenous administration of clonidine
      hydrochloride (2 micrograms/kg) was assessed in 16 patients with DSM-III-R social
      phobia, 13 patients with DSM-III-R panic disorder, and 31 healthy controls.
      Compared to the healthy volunteers, both social phobic and panic-disorder
      patients had significantly blunted GH increments after clonidine. The social
      phobic patients demonstrated a similar degree of GH "blunting" to clonidine as
      did the patients with panic disorder.

PMID- 8292688
TI  - Beta-adrenergic receptor binding in frontal cortex from suicide victims.
AB  - Beta-adrenergic binding in frontal cortex samples from suicide victims has been
      reported to be increased, unaltered, and decreased compared to matched controls.
      Subject's diagnoses and drug exposures in these studies were not equivalently
      documented and were possibly different. In the present study, diagnostic and
      symptomatic information was systematically collected from family members of 15
      subjects committing suicide and 15 matched controls using standardized interview
      techniques. The goal was to test the hypothesis that alterations in beta
      adrenergic binding were more likely to be found in subjects with evidence of
      depressive disorders. [125I]pindolol binding in frontal cortex was found to be
      significantly lower in the group committing suicide compared to the matched
      controls (21.1 +/- 1.1 fmol/mg protein vs. 24.8 +/- 0.8 fmol/mg protein, p <
      .02). However, no diagnostic subgroup among the suicide victims appeared
      distinct.

PMID- 8292689
TI  - Convulsive threshold differences in right unilateral and bilateral ECT.
AB  - This study examines how the convulsive threshold in electroconvulsive therapy
      (ECT) varies with electrode placement (bilateral [BL] versus right unilateral
      [RUL]), age, gender, weight, and the nasion-inion measurements of the head.
      METHOD: Twenty-eight subjects underwent stimulus dose titration to determine the
      convulsive threshold. Titration was accomplished for each subject with both
      electrode placements during the first and second ECT in a balanced design. Head
      measurements were made prior to the first ECT. Results indicated that the
      convulsive threshold was higher for BL than RUL, higher for men than women,
      increased with age, and increased with an increasing nasion-inion measurement in
      women but not in men. We concluded that the convulsive threshold varies according
      to the choice of electrode placement, gender, and age as has been reported by
      others. We additionally report that the convulsive threshold increases with
      increasing head size as reflected in the nasion-inion distance.

PMID- 8292690
TI  - Volumetric magnetic resonance imaging in men with dementia of the Alzheimer type:
      correlations with disease severity.
AB  - Using magnetic resonance imaging (MRI), we measured the volumes of various brain
      structures and cerebrospinal fluid (CSF) in 19 men with dementia of the Alzheimer
      type (DAT) and 18 healthy age-matched control men. The mean (+/- S.D) Mini-Mental
      State exam score (MMSE) of the DAT men was 16 +/- 7; 9 were mildly (MMSE > 20), 5
      moderately (MMSE 10-20), and 5 severely (MMSE < 10) demented. Brain and CSF
      volumes were normalized as a percent of the traced intracranial volume to control
      for the relation of volumes of cerebral structures to head size, and analyzed
      statistically. The whole group of DAT subjects had significantly smaller mean
      cerebral brain matter and temporal lobe volumes (p < 0.05), and significantly
      larger mean ventricular and temporal lobe peripheral CSF volumes than did
      controls. Mean volumes of the subcortical nuclei did not differ significantly
      between groups, and mean volume of temporal lobe brain matter decreased
      significantly more than whole brain, suggesting regional loss of brain matter in
      DAT. Mildly demented DAT patients had significantly smaller mean cerebral brain
      matter and temporal lobe volumes and significantly larger volumes of lateral
      ventricles, and of temporal lobe peripheral CSF, than did controls.
      Neuropsychological measures of disease severity in DAT patients were
      significantly (p < 0.05) and appropriately correlated to volumes of cerebral
      brain matter and right lateral ventricle. These results suggest that in DAT: (i)
      significant brain atrophy is present early in the disease process, (ii) brain
      atrophy correlates with severity of cognitive impairment, and (iii) there is
      greater involvement of the telencephalic association system than whole brain, and
      there is relative sparing of the caudate, lenticular and thalamic nuclei.

PMID- 8292691
TI  - Disordered water homeostasis and cognitive impairment in schizophrenia.
AB  - To investigate a possible association between disordered water homeostasis and
      cognitive impairment in schizophrenia, neuropsychological tests were applied to
      16 schizophrenic patients with severely deranged water homeostasis and to 16
      matched schizophrenic controls. The patients with disordered water homeostasis
      tended to obtain poorer scores than the controls throughout, the differences
      being statistically significant for two of the tests (Wechsler Memory Scale
      Visual Reproduction and Trial Marking Test part A). These results were not
      ascribable to differences in the duration of the illness, premorbid IQ,
      medication, or electroconvulsive therapy received, or prominence of any
      particular symptoms. The results suggest the co-existence of disordered water
      homeostasis and cognitive impairment in a subset of schizophrenic patients.

PMID- 8292692
TI  - Enzyme elevations in the neuroleptic malignant syndrome.
AB  - Enzyme elevations are frequently observed in neuroleptic malignant syndrome
      (NMS), but their significance is unknown and their source is uncertain. In this
      study the relationship of serum enzymes to creatine phosphokinase (CPK) in NMS is
      examined. Thirty-seven patients with at least one probable episode of NMS were
      studied, and 83 consecutive newly admitted psychiatric patients constituted a
      comparison group. Serum levels of lactate dehydrogenase (LDH), glutamic
      oxaloacetic transaminase (GOT), aldolase, and alkaline phosphatase (AP) were
      compared to serum CPK levels in each patient group. Except for AP, all enzymes
      were significantly correlated with CPK in both groups. However, correlations were
      much higher in the NMS group, and regression lines for CPK-LDH and CPK-GOT pairs
      differed significantly between patient groups. These data strongly suggest that a
      common process underlies the enzyme elevations frequently seen in NMS, that these
      enzymes originate in muscle tissue, and that these findings are not caused solely
      by agitation or psychological stress. It is likely that increased production and
      selective "leakage" of enzymes from myocytes play a role in this process.

PMID- 8292693
TI  - Elevated PLA2 activity in schizophrenics and other psychiatric patients.
AB  - We measured serum phospholipase A2 (PLA2) activity in 39 schizophrenics, 26
      psychiatric controls, and 26 normal controls using a radioenzymatic assay with
      phosphatidylcholine as precursor. Serum PLA2 activity was significantly higher in
      schizophrenics (p = 0.002) and other psychiatric (including substance abusing)
      patients (p = 0.032) than in normal controls. Enzyme activity did not differ
      between the schizophrenic patients and psychiatric controls. Fifty-one percent of
      the schizophrenics and 46% of psychiatric controls had PLA2 values above the
      highest value for normal controls. In the psychiatric control group higher than
      normal PLA2 activities were observed in all diagnostic categories, including
      major depression, bipolar disorder, posttraumatic stress disorder (PTSD), and
      substance abuse. In the context of others' findings of increased circulating PLA2
      in infectious and inflammatory conditions, these increases must be viewed as
      disease nonspecific. The significance of these changes and their relationship to
      other acute-phase protein changes needs to be clarified in future research.

PMID- 8292694
TI  - The influence of DST and TRH test administration on depression assessments: a
      controlled study.
AB  - Significant antidepressant effects have been reported after administration of
      dexamethasone and thyrotropin-releasing hormone (TRH). The purpose of this study
      was to evaluate whether or not the administration of the dexamethasone
      suppression test (DST) and TRH test in depressed patients, just before their
      entering clinical trials, has any impact on their symptoms. The Hamilton Rating
      Scale for Depression was administered to 166 subjects at screen visit, 1 week
      later (baseline visit), and 1 week after beginning treatment with fluoxetine 20
      mg/day (week-1). Between screen and baseline visits, 62 patients were
      administered the DST alone, 6 underwent the TRH test alone, and 26 received both
      the DST and the TRH test. Seventy-two patients were not administered either test.
      No statistically significant differences in depression scores were found at
      screen, baseline and week-1 visits between patients who underwent neuroendocrine
      tests and those who did not. Our data suggest that the administration of
      neuroendocrine tests such as the DST and the TRH test does not have a
      statistically significant effect on depressive symptoms and, therefore, does not
      interfere with study results and interpretation.

PMID- 8292695
TI  - Plasma-free and sulfoconjugated MHPG in major depressive disorders: differences
      between responders to treatment and nonresponders.
AB  - The plasma levels of free and sulfoconjugated forms of 3-methoxy-4
      hydroxyphenylglycol (MHPG) were examined before and after treatment in 16
      patients with unipolar major depressive disorders without melancholia. The
      patients were treated with intravenous administration of clomipramine for 4
      weeks. Seven depressive disorder patients who showed marked improvement (the
      improvement group) revealed significant reduction in their plasma sulfoconjugated
      MHPG levels. In 6 depressive disorder patients who showed no improvement (the no
      improvement group), the plasma sulfoconjugated MHPG levels showed no significant
      change after treatment. The remaining 3 patients, who showed ambiguous change
      after treatment, were excluded from the analysis. Levels of plasma-free MHPG
      showed significant change after treatment in neither the improvement group nor in
      the no-improvement group. It is suggested that levels of plasma sulfoconjugated
      MHPG may serve as an indicator of brain noradrenergic activity.

PMID- 8292696
TI  - An association between increased concentrations of cerebrospinal fluid dopamine
      sulfate and higher negative symptom scores in patients with schizophrenia and
      schizoaffective disorder.

PMID- 8292697
TI  - Buspirone-induced hypothermia in normal male volunteers.

PMID- 8292698
TI  - Not significantly different is not the same as significantly similar.

PMID- 8292699
TI  - [Liver transplantation--current perioperative developments].

PMID- 8292700
TI  - [Potentialities and limitations of the score system in intensive medicine].
AB  - In intensive-care medicine, score systems serve to quantify the severity of
      diseases and to characterise patient groups on the basis of objective criteria.
      The principle is to describe the severity by adding up points. Objectives are to
      assess the prognosis, to establish the amount of treatment required and assist in
      clinical decision making. The most important examples of general scores covering
      more than one disease are Acute Physiology And Chronic Health Evaluation (APACHE
      II, APACHE-III), Simplified Acute Physiology Score (SAPS) and Mortality
      Prediction Model (MPM). General scores assess the deviation of physiological
      parameters from the normal assuming that the degree of deviation reflects the
      severity of the disease. The Therapeutic Intervention Scoring System (TISS)
      constitutes a particular form which evaluates exclusively the amount of therapy
      required. Disease-specific scores (trauma scores, sepsis scores) take into
      account the fact that the nature and stage of specific disease determine the
      outcome in a typical way. Scores are adequately validated and suitable for
      evaluation of clinical studies or cost-benefit analyses by characterisation of
      patient populations. The use of score systems for individual prognosis is at
      present controversial. Their clinical significance might increase in that scores
      help to make medical decisions by contributing to early identification of
      endangered patients by systematic establishment and evaluation of investigation
      results. Scores are likely to be used increasingly in intensive-care medicine.

PMID- 8292701
TI  - [Preoperative risk factors and intraoperative and postoperative risk management
      in 11,890 anesthesias. Initial results of a prospective study].
AB  - OBJECTIVE: The relation of the frequency and severity of pitfalls, events and
      complications (PECs) was analysed in respect of preoperative risk factors. The
      epidemiological data were gathered as a contribution to a current project of the
      German Society for Anaesthesiology and Intensive Care. METHOD: Preoperative data
      (age, sex, preexisting diseases, pathological findings, grade of urgency and ASA
      class) were integrated in a paper record, as well as the perioperative
      interventions and directly postoperative events, type of anaesthesia, and kind of
      operation. The automatically readable paper records were routinely in use for
      every patient. After control and correction the data were stored in a modern data
      base. MAIN RESULTS: From October 1, 91 to May 20, 92 11,890 anaesthesias were
      recorded. 2,959 of them with a total of 4,184 PECs. 2,397 PECs were
      cardiovascular, 875 respiratory. PECs of grade I (no impact on treatment in the
      recovery room [RR]) occurred in 14% of patients, grade II (impact on treatment in
      RR, but no impact on discharge to ward) 7.2%, grade III (prolonged stay in RR or
      special monitoring in the ward) 2.88%; grade IV (PEC leads to transfer to the
      ICU) 0.63%, and grade V (PEC leads to disabling damage or death) 0.13%. 13 of 15
      patients suffering from PECs grade V were of ASA class 4 or 5. PECs had a certain
      relation to the ASA-classification of anaesthetic risk. But this relation is
      quite different in several surgical disciplines. CONCLUSIONS: Preoperatively
      known risk factors of the patient and the measures taken by specialists of
      various disciplines contribute to the incidence of PECs. Available data could be
      processed multicentrally and in standard form for producing prognostic data for
      risk prediction. Since PECs of grade II or higher are cost- relevant, requiring
      an interdisciplinary approach, it appears meaningful to base costing on such an
      interdisciplinary approach in accordance with the requirements of diagnosis and
      treatment.

PMID- 8292702
TI  - [Pharmacodynamic effects of the phosphodiesterase inhibitor enoximone during
      exposure to the volatile anesthetics halothane and isoflurane in coronary surgery
      patients].
AB  - AIM OF THE STUDY: We investigated the pharmacodynamic effects of the
      phosphodiesterae inhibitor enoximone in the presence of halothane and isoflurane
      in 20 patients, ASA class III, aged 45-75 years, undergoing coronary artery
      bypass grafting. The study was approved by the local Medical Ethics Committee and
      patients' informed written consent was obtained. METHODS: After induction of
      anaesthesia (midazolam, fentanyl, etomidate and pancuronium) all patients
      received either halothane 1 MAC (group I, n = 10) or isoflurane 1 MAC (group II,
      n = 10), followed 20 min later by enoximone 0.5 mg/kg. Haemodynamic variables
      were measured and blood samples (arterial, mixed venous) were obtained before the
      administration of the volatile anaesthetics (control, t0), immediately (t1) and 5
      (t2) min after steady state conditions with halothane or isoflurane, as verified
      by the end-expiratory concentration and 5 (t3) and 10 (t4) min after the
      injection of enoximone. Heart rate (HR), mean arterial pressure (MAP), mean
      pulmonary artery pressure, pulmonary capillary wedge pressure and right atrial
      pressure were recorded. Cardiac (CI) and stroke volume indices, systemic (SVR)
      and pulmonary vascular resistance, oxygen availability (AO2) oxygen consumption
      and oxygen extraction rate were calculated using standard formulae. RESULTS: In
      both groups HR remained essentially unchanged throughout the investigation
      period. MAP decreased significantly in both groups under steady state conditions
      with the volatile anaesthetics (group I: 19%; group II: 30%) but remained
      unchanged after subsequent injection of enoximone. After administration of
      halothane SVR remained essentially unchanged, whereas isoflurane decreased SVR
      significantly by 20%. After enoximone, there was a significant decrease in SVR in
      both groups (group I: 26%; group II: 25% compared with the values obtained after
      halothane and isoflurane respectively). Halothane and isoflurane decreased CI
      significantly and to a similar degree (group I: 17%; group II: 17%). After the
      injection of enoximone CI increased significantly and reached control values in
      both groups. AO2 decreased significantly after administration of the volatile
      anaesthetics (group I: 19%; group II: 21%) and increased significantly after
      administration of enoximone, returning to control values. Halothane (7%) and
      isoflurane (13%) produced a significant increase in oxygen extraction. After
      bolus injection of enoximone oxygen extraction decreased significantly and
      returned to control value in group II. In group I enoximone decreased oxygen
      extraction significantly compared with control. CONCLUSION: Our results suggest
      that in the presence of halothane or isoflurane the phosphodiesterase inhibitor
      enoximone produces a comparable increase in cardiac output and decrease in
      systemic vascular resistance in patients with coronary artery disease.

PMID- 8292703
TI  - [Anesthesia for patients with pheochromocytoma. Our own results and a review].
AB  - Phaeochromocytoma is a rare, autonomous catecholamine secreting tumour of the
      sympatho-adrenergic system. Due to the continuous or phasic secretion of
      catecholamines from the tumour, patients present with hypertensive crisis,
      episodic or sustained hypertension or arrhythmia. Excessive intraoperative
      hypertension unable to control by usual methods should be considered to be a
      phaeochromocytoma. Surgical removal of identified lesions should be performed
      under controlled conditions and after sufficient preparation of the patient.
      Preoperative alpha-adrenergic blockade with prazosin and phentolamine allows an
      increase in intravascular volume and affords some protection against excessive
      intraoperative hypertension. The use of beta-adrenergic antagonists is only
      recommended in patients with arrhythmia (especially tachycardia) and after
      induction of alpha-adrenergic blockade. For operation of phaeochromocytoma,
      modified neuroleptic anaesthesia is a useful anaesthetic technique.
      Intraoperative hypertension is controlled with sodium nitroprusside and
      phentolamine. Intravascular volume is substituted under CVP or PAP control, and
      epinephrine or norepinephrine are used if necessary. During the postoperative
      period, hypotension or hypertension or left ventricular failure may occur. In an
      own study, 9 patients with phaeochromocytoma were investigated, 7 patients with
      other operations of the adrenal glands served as controls. Despite specific
      preoperative preparation and intraoperative use of antihypertensive drugs,
      excessive increases in blood pressure could not be avoided in some cases.
      Extremely high plasma levels of catecholamines up to the factor 1,000 of the
      normal range were found. Even in controls, considerable increases in blood
      pressure and catecholamine levels were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292704
TI  - [The liver and anesthesia].

PMID- 8292705
TI  - [The importance of the cytochrome P-450 superfamily in the metabolism of an
      anesthesia relevant drug].

PMID- 8292706
TI  - [Hepatotoxicity of inhalation anesthetics].

PMID- 8292707
TI  - [Anesthesia in liver insufficiency].

PMID- 8292708
TI  - [Anesthesia in liver transplantation].

PMID- 8292709
TI  - [Historical vignette--Ether explosions].

PMID- 8292710
TI  - [Anesthesia with propofol during an exacerbated course of acute intermittent
      porphyria].
AB  - In the eighth week of pregnancy the medical indication for induced abortion was
      established due to an exacerbating acute intermittent porphyria with life
      threatening neurological symptoms. delta-aminolaevulinic acid and porphobilinogen
      were excessively increased in urine prior to the operation. Anaesthesia was
      induced with a bolus of propofol, alfentanil and droperidol, maintained by 67% of
      nitrous oxide and small bolus injections of the three drugs. The patient regained
      consciousness immediately after the operation, and reached full orientation and
      cooperativeness within five minutes. The postoperative period remained uneventful
      and the neurological and psychological symptoms returned to the pre-exacerbation
      status. Chorion gonadotropins and porphyria markers decreased within the next
      four weeks accompanied by a simultaneously progressing clinical improvement. The
      use of propofol and the other drugs appears justified even in exacerbated
      porphyria.

PMID- 8292711
TI  - [Struma as a cause of a brachialgia].
AB  - A 76-year-old woman with a great multi-nodular goitre and no neurological
      deficits suffered from increasing pain of the lateral upper arm. A combination of
      nerve blockades and physical measures was not effective in terms of continuous
      pain control. Subtotal thyroidectomy resulted in a long-term complete pain
      relief. The underlying mechanism is explained as a compression of the superior
      trunk of brachial plexus by a goitre. In future a goitre should be taken into
      consideration in the aetiology of a brachialgia.

PMID- 8292712
TI  - Effects of extracellular matrix components on cell locomotion.
AB  - The extracellular matrix (ecm), which is composed of collagens, glycoproteins,
      and proteoglycans, has emerged as an important regulator of cell locomotion. This
      review describes some of the mechanisms by which the ecm may regulate locomotion,
      focusing primarily on cell extension and lamellae formation. Ecm-receptor
      interactions form an important part of cell recognition of ecm. Such interactions
      can result in altered cell adhesion, signal transduction, and cytoskeletal
      organization, all of which impact on cell locomotion. It is important to note
      that although the effects of single ecm components have been studied, generally,
      the cell is likely to perceive ecm in vivo as a macromolecular complex. It will
      fall to future work to define how complexes of ecm regulate cell behavior.
      Because of our own particular research bias, we focus on reviewing the role of
      fibronectin, integrins, chondroitin sulfate, hyaluronan, and hyaluronan receptors
      in the regulation of cell locomotion and examine their effect on adhesion, signal
      transduction, and cytoskeletal integrity. Cytoskeleton assembly mechanisms,
      particularly those that might be regulated by the ecm, are also described. These
      events are summarized in a working model of ecm-promoted locomotion.

PMID- 8292713
TI  - Current status of histogenetic and morphogenetic concepts of salivary gland
      tumorigenesis.
AB  - Because of their complexity and relative infrequency, salivary gland tumors
      commonly result in diagnostic problems. Histogenetic and morphogenetic concepts
      of tumorigenesis in these glands are reviewed and their relevance to routine
      diagnosis and classification of salivary gland tumors evaluated. Evidence is
      presented from animal and human studies that under steady-state and
      pathophysiological conditions, all cell types present in the normal gland,
      including acinar cells, are capable of rapidly entering the cell cycle and are,
      therefore, possible targets for neoplastic transformation.

PMID- 8292714
TI  - Dentinogenesis.
AB  - The formation of dentin, dentinogenesis, comprises a sophisticated interplay
      between several factors in the tissue, cellular as well as extracellular. Dentin
      may be regarded as a calcified connective tissue. In this respect, as well as in
      its mode of formation, it is closely related to bone. Using dentinogenesis as an
      experimental model to study biomineralization provides several practical
      advantages, and the results may be extrapolated to understand similar processes
      in other tissues, primarily bone. After describing dentin structure and
      composition, this review discusses items such as the morphology of
      dentinogenesis; the dentinogenically active odontoblast, transport, and
      concentrations of mineral ions; the constituents of the dentin organic matrix;
      and the presumed mechanisms involved in mineral formation.

PMID- 8292715
TI  - Role of growth factors in cutaneous wound healing: a review.
AB  - The well-orchestrated, complex series of events resulting in the repair of
      cutaneous wounds are, at least in part, regulated by polypeptide growth factors.
      This review provides a detailed overview of the known functions, interactions,
      and mechanisms of action of growth factors in the context of the overall repair
      process in cutaneous wounds. An overview of the cellular and molecular events
      involved in soft tissue repair is initially presented, followed by a review of
      widely studied growth factors and a discussion of commonly utilized preclinical
      animal models. The article concludes with a summary of the preliminary results
      from human clinical trials evaluating the effects of growth factors in the
      healing of chronic skin ulcers. Throughout, the interactions among the growth
      factors in the wound-healing process are emphasized.

PMID- 8292716
TI  - Structural requirements for tissue factor pathway inhibitor interactions with
      factor Xa and heparin.
AB  - Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type protease
      inhibitor, which inhibits factor Xa directly and in a factor Xa dependent manner
      inhibits the factor VIIa/tissue factor catalytic complex. Altered forms of
      recombinant TFPI (rTFPI) were tested for their ability to inhibit human factor Xa
      and bovine gamma-carboxyglutamate (Gla)-domainless factor Xa in the presence and
      absence of calcium ions, heparin, phospholipids, and factor Va. Sequential
      deletions of the positively charged C-terminus of TFPI produces proteins that
      have decreasing inhibitory activity against factor Xa as well as decreasing
      affinity for heparin-agarose. Deletion of the C-terminus distal to Leu181, which
      eliminates the third Kunitz-type domain, results in the loss of heparin-agarose
      binding at physiological ionic strength. Furthermore, the entire C-terminal
      polypeptide, including at least a portion of the third Kunitz-type domain,
      appears to be involved in heparin binding. Residues 230-241 probably form an
      alpha helix in which Lys231 and Arg237 within the Kunitz domain and Lys240 and
      Lys241 could provide a positively charged surface epitope capable of binding
      heparin. Heparin and Ca2+ together, but not individually, enhance the rate of
      factor Xa inhibition by full-length TFPI. The effect of heparin is concentration
      dependent and biphasic (maximal between 0.1 and 1.0 unit/ml) suggesting that the
      acceleration of factor Xa inhibition occurs at least in part through a 'template'
      mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292717
TI  - The mutation in fibrinogen Bicetre II (gamma Asn308-->Lys) does not affect the
      binding of t-PA and plasminogen to fibrin.
AB  - The aim of this study was to investigate the interactions of t-PA and plasminogen
      with fibrin derived from an abnormal fibrinogen detected in a 40-year-old male
      patient who had had an episode of thrombophlebitis with pulmonary embolism. An
      abnormal fibrinogen was diagnosed on the basis of prolonged thrombin and
      reptilase times also detected in two other family members. Fibrinogen purified
      from plasma, in the presence of protease inhibitors, by glycine precipitations,
      gel filtration and affinity chromatography, was devoid of plasminogen,
      fibronectin, and vWf. SDS-PAGE analysis according to Laemmli under reducing
      conditions, showed an abnormal gamma chain (approximately 50% of the total)
      migrating in a more anodic position (M(r) 48 kDa). By PCR amplification and DNA
      sequencing, the abnormality was identified as an Asn308-->Lys mutation of the
      gamma chain. Since such a mutation constitutes a new plasmin cleavage site as
      first reported for fibrinogen Kyoto I, it may modify interactions of plasminogen
      and t-PA with carboxy-terminal lysine residues. Ligand-binding studies were
      therefore performed using intact and plasmin-degraded fibrin surfaces obtained
      from the abnormal fibrinogen. The plasminogen and t-PA binding isotherms obtained
      with the abnormal fibrinogen were similar to the control. Moreover, the
      stimulation by fibrin of plasminogen activation by t-PA was not different from
      the control. These results suggest (i) that the lysine 308 residue may not be
      exposed to plasmin cleavage in fibrin, and (ii) that the thrombotic accident of
      the propositus cannot be explained by an abnormality of the plasminogen/t-PA
      binding to fibrin.

PMID- 8292718
TI  - Effect of ioxaglate--an ionic low osmolar contrast medium--on fibrin
      polymerization in vitro.
AB  - Ioxaglate, an iodinated contrast agent, decreases the rates of fibrin clot
      formation induced by thrombin or reptilase. This effect is not related to an
      increase in the ionic strength of the medium since a specific control of
      equivalent composition does not induce such variation. The concentration of
      ioxaglate which led to a 50% decrease of the control clot turbidity induced by
      thrombin was 17.5 +/- 2 mM. Macroscopically, clots formed with ioxaglate were
      larger and less turbid than the isotonic control. An increase in fibrin fibre
      diameters and a decrease in their densities were observed. During the fibrin
      polymerization process, all the fibrinogen was converted into fibrin, as for both
      the control and ioxaglate quantitative analysis of clots and supernatants showed
      (1) an identical quantity of FpA in clot supernatants, (2) the same quantities of
      protein incorporated into clots, and (3) no trace of fibrin monomers in the clot
      supernatants. Furthermore, dissolution in urea of clots formed in the presence of
      ioxaglate occurred more rapidly than in the control. Total incorporation of
      fibrinogen into clots, associated with a decrease in clot turbidity, indicated
      the existence of a qualitative abnormality in the construction of the three
      dimensional fibrin structure. Using differential scanning calorimetry, it was
      observed that the two domains (D and E) of fibrinogen were modified by ioxaglate,
      showing the absence of specificity in the interaction between ioxaglate and a
      particular domain.

PMID- 8292719
TI  - The effect of two-domain tissue factor pathway inhibitor on endotoxin-induced
      disseminated intravascular coagulation in rabbits.
AB  - Disseminated intravascular coagulation (DIC) is a common complication in sepsis,
      and may result from endotoxin-induced exposure of tissue factor on the surface of
      monocytes and endothelial cells. Tissue factor pathway inhibitor (TFPI) is a
      factor Xa-dependent feedback inhibitor of the tissue factor-factor VIIa complex.
      In the present study the effect on DIC of a two-domain TFPI analogue (2D-TFPI),
      consisting of the first two Kunitz domains of TFPI but lacking the third domain,
      was tested. DIC was induced in rabbits by two intravenous bolus injections of
      endotoxin from Escherichia coli (10 and 50 micrograms/kg) 24 h apart.
      Simultaneously with the last endotoxin injection an infusion of 2D-TFPI (0, 0.3,
      1.0 or 3.0 mg/kg/h) was given. Blood samples were obtained at 0 h, 24 h and 31 h.
      At 31 h the animals were sacrificed and the kidneys were submitted to
      histological examination. The degree of fibrin deposition in glomeruli was scored
      blindly using an arbitrary scale from 0 to 3. Between 24 and 31 h the group
      receiving endotoxin alone showed a significant decrease in platelet count (65%),
      plasma fibrinogen (41%), antithrombin III (25%), and factor VIII (63%), and a
      significant prolongation of the aPTT (14%). Furthermore, massive fibrin
      deposition was detected in the renal glomeruli at 31 h. Infusions of 2D-TFPI
      inhibited all the endotoxin-induced changes in a dose-dependent manner. In
      conclusion, the data demonstrate that inhibition of the TF/FVIIa complex by
      infusion of 2D-TFPI significantly counteracts endotoxin-induced coagulopathy in
      rabbits, and might thus be an attractive drug for treatment of endotoxin-induced
      DIC in humans.

PMID- 8292720
TI  - Evidence that the C-terminus of tissue factor pathway inhibitor (TFPI) is
      essential for its in vitro and in vivo interaction with lipoproteins.
AB  - We have previously shown that the C-terminus of TFPI is essential for its
      anticoagulant activity. In the present study we have assessed the role of this
      region in the binding of TFPI to lipoproteins. We found that full length TFPI,
      but not C-terminal degraded TFPI, was capable of coeluting with the plasma
      lipoprotein fraction on a Superose-6 column. The importance of the TFPI C
      terminus in lipoprotein interactions was also assessed using a microtitre plate
      binding assay. We found that full-length TFPI was capable of binding to VLDL or
      LDL coated microtitre plates. C-terminal degraded TFPI also bound to VLDL, but
      with a ten-fold lower affinity than full length TFPI. Interestingly, removal of
      the C-terminus along with the third Kunitz-type domain resulted in a TFPI form
      incapable of lipoprotein binding. Since heparin shows strong binding to the C
      terminus of TFPI, we also tested its effect on the binding of full length TFPI to
      VLDL. We found that co-incubation of TFPI with heparin inhibited this binding in
      a dose-dependent manner. Heparin was also capable of releasing TFPI from a
      preformed TFPI:VLDL complex, although this reaction required unphysiological
      amounts of heparin. To assess the physiological function of heparin on FL
      TFPI:lipoprotein interactions we also performed gel filtration chromatography of
      rabbit plasma immediately following i.v. administration of FL-TFPI with and
      without heparin. Previous experiments indicated that heparin has a protective
      effect on exogenously added FL-TFPI, increasing its recovery by ten
      fold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292721
TI  - Effects of low molecular weight heparins on fibrin polymerization and clot
      sensitivity to t-PA-induced lysis.
AB  - We have previously demonstrated that therapeutic concentrations of unfractionated
      heparin (UFH) impair fibrin polymerization leading to the formation of clots
      which are more sensitive to lysis induced by tissue plasminogen activator (t-PA).
      The aim of this study was to compare the effect of UFH with that of three
      different low molecular weight heparins (LMWHs) on clot sensitivity to t-PA
      induced lysis. Labelled fibrin clots, prepared from plasma containing UFH,
      Fraxiparine, Reviparine, Enoxaparine or saline, were incubated in phosphate
      buffer containing t-PA (0.1 and 0.5 microgram/ml) and plasminogen (20
      micrograms/ml). The extent of clot lysis was quantified by counting the residual
      radioactivity of the clots and by measuring D-dimer levels released into the
      medium. Fibrin polymerization and clot structure were evaluated by means of a
      turbidimetric assay and by electron microscopic scanning. Pre-incubation of
      plasma with 0.5 or 1.0 U/ml UFH resulted in a marked dose-dependent acceleration
      of lysis induced by 0.1 or 0.5 microgram/ml t-PA. In contrast, lysis rates
      induced by 0.5 microgram/ml t-PA were not modified by pre-incubation of plasma
      with LMWHs. When exposed to 0.1 microgram/ml t-PA clots formed from plasma
      containing 0.5-2 IU/ml of Fraxiparine, Reviparine and Enoxaparine showed only a
      minor increase in lysis rates compared to control clots. There was not a clear
      dose-response curve with LMWHs. Furthermore, lysis rates obtained with UFH
      treated clots were always significantly higher than those seen with LMWHs-treated
      clots.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292722
TI  - Flow cytometric observations on the in vivo use of Fab fragments of a chimaeric
      monoclonal antibody to platelet glycoprotein IIb-IIIa.
AB  - Fluorescence flow cytometry (FC) was employed to monitor the platelet surface in
      humans receiving intravenous infusions of Fab fragments of a chimaeric
      (murine/human) construct of monoclonal antibody 7E3, which binds to the
      fibrinogen receptor (glycoprotein IIb-IIIa) and inhibits platelet aggregation.
      Platelet surface-bound chimaeric 7E3-Fab (c7E3-Fab) was measured using a
      fluorescein-conjugated polyclonal anti-7E3 antibody and residual c7E3-Fab binding
      capacity was measured using fluorescein-conjugated c7E3-Fab. Turbidometrically
      measured platelet aggregation response to ADP was shown to be a linear function
      (r = 0.9) of the logarithm of residual free binding sites for c7E3-Fab. The
      distribution of c7E3-Fab in the platelet population was unimodal at all time
      points following the infusion, demonstrating in vivo transfer of antibody to
      newly released circulating platelets. Clearance of platelet surface-bound
      antibody followed an exponential model but all circulating platelets were bearing
      c7E3-Fab at time points well beyond the lifespan of the platelets exposed to c7E3
      Fab during the infusion. Ex vivo and in vitro mixing experiments showed that c7E3
      Fab transfer between platelets was possible and suggested that differences in the
      in vivo kinetics between monovalent and bivalent forms of monoclonal antibodies
      might be relevant in their therapeutic application.

PMID- 8292723
TI  - Reversal of excessive effect of regular anticoagulation: low oral dose of
      phytonadione (vitamin K1) compared with warfarin discontinuation.
AB  - To determine the best way to reverse the excessive effect of regular
      anticoagulation in patients with INR > 5 and no bleeding complications, 23
      patients with INR > 5 were randomly subdivided into two groups: group A (n = 12)
      discontinued warfarin for one day and group B (n = 11) received 2 mg of vitamin
      K1 orally in addition to the usual warfarin dose. INR was determined after 24 h
      (day 1), after which both groups continued with their usual dose of warfarin.
      After 48 h (day 2), warfarin dosage was changed according to the INR value. On
      day 9, INR values were determined again. Five out of twelve patients in group A
      had INR values > 5 on day 1. One patient in group A had an INR value < 5 both on
      days 1 and 2. All eleven patients in group B had INR values < 5 on day 1, and all
      but one on day 2. On day 9, INR values were acceptable (INR 2.0-4.5) in ten group
      A patients and eight group B patients. These findings suggest that a low oral
      dose of vitamin K1 is a convenient treatment for excessive anticoagulation in
      patients with no bleeding complications.

PMID- 8292724
TI  - Intrinsic procoagulant surface induced by hypercholesterolaemia on rabbit aortic
      endothelium.
AB  - The effect of hyperlipidaemia on endothelial cell haemostatic properties was
      examined using ex vivo studies on aortic segments obtained from fat-fed
      Chinchilla rabbits, mounted in a template device which exposed the luminal
      surface. Exposure of arterial endothelium to lipids resulted in marked
      enhancement of externally exposed anionic phospholipids, detected using either
      fluorescence microscopy with the probe merocyanine 540 or by binding of 125I
      polymyxin B and 125I-Annexin V. Consistent with the known procoagulant properties
      of anionic phospholipid, following the lipid and cholesterol-rich diet intake,
      intact endothelial cells demonstrated enhanced binding of radioiodinated factors
      IX/IXa and Xa, and enhanced factor IXa/VIII-dependent factor X activation and
      factor Xa-factor Va-mediated prothrombin activation. Both factor Xa and thrombin
      formation were blocked, in large part, by polymyxin B, suggesting dependence of
      the reaction on anionic phospholipids. Consistent with these results, evidence of
      increased activation of the coagulation mechanism in vivo was observed in
      hyperlipidaemic animals, as assessed by a three-fold increase in levels of
      circulating antithrombin-protease complexes, compared with normolipidaemic
      controls.

PMID- 8292725
TI  - Incidence of inhibitors in haemophiliacs. A review of the literature.
AB  - The development of factor VIII inhibitors remains one of the most serious
      complications in the treatment of patients with haemophilia A. Previous studies
      show a broad range of inhibitor prevalences (3.6-25.0%). Recent prospective
      studies, especially with monoclonal and recombinant factor VIII products, have
      given rise to discussion as to whether such preparations increase the incidence
      of inhibitors. Thirteen published inhibitor studies (as of January 1993) have,
      therefore, been analysed with regard to their design, results and evaluation.
      Most older studies were performed retrospectively and only evaluated the
      percentage of inhibitors in a poorly defined patient population at a given time.
      There was no clear differentiation between children and adults. Eleven studies
      showed incidence data, i.e. new inhibitors within the study period in a well
      defined group. One study included only multi-transfused adults and the inhibitor
      incidence was only 2.4%. All other studies showed incidence rates of 5.7-32.0%.
      The new prospective studies, in particular, clearly confirm the early observation
      that young children with severe haemophilia A are at highest risk of inhibitor
      development after relatively few exposure days (median 9-15 days, one study 25
      days). The early conclusion that monoclonally purified or recombinant factor VIII
      products may cause higher inhibitor rates was not confirmed by the newer studies.
      Previously untreated patients with severe haemophilia A showed inhibitor rates
      between 10% (Hemofil M) and 52% (various concentrates of different purity and
      viral inactivation method). One study evaluating such patients reveiving only
      intermediate purity products or cryoprecipitate showed an incidence of
      28%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292726
TI  - Thrombin interactions with cells of the megakaryocytic lineage.
AB  - Thrombin is a potent physiological platelet agonist, critical for haemostasis and
      thrombosis. Several studies have recently demonstrated that thrombin also
      displays functional effects on bone marrow platelet progenitors, i.e. the
      megakaryocytes, and possibly on megakaryocyte precursors. Following a brief
      description of the different cell systems used for these investigations, this
      paper focuses on data related to thrombin receptors, their coupling mechanisms,
      and biological responses due to their activation on cells of the megakaryocytic
      lineage. In spite of some differences, whose significance remains to be
      established, most data reported give evidence of considerable homologies in
      thrombin receptors and signal transduction mechanisms between platelets and cells
      belonging to the megakaryocytic lineage. In addition, a potential functional role
      for thrombin in the regulation of megakaryocytopoiesis is emerging. The
      physiological relevance of these observations are discussed.

PMID- 8292727
TI  - The role of fibronectin in macrophage fibrin binding: a potential mechanism for
      high affinity, high capacity clearance of circulating fibrin.
AB  - Fibrin generation occurs as the result of a wide variety of pathological
      conditions. Extraneous deposition of fibrin outside a wound or inflammatory locus
      can lead to severe circulatory and respiratory complications. Fibrin within the
      circulation is removed by the hepatic macrophage (Kupffer cell). While many
      mechanisms for macrophage fibrin binding have been delineated in vitro, the
      complete pathway for in vivo fibrin clearance has not been determined. This
      article reviews these varied mechanisms and describes in detail a novel potential
      fibronectin-dependent pathway for hepatic fibrin clearance.

PMID- 8292728
TI  - Effect of splenectomy on von Willebrand factor multimeric structure in thrombotic
      thrombocytopenic purpura refractory to plasma exchange.
AB  - Treatment-related changes in plasma von Willebrand factor (vWf) multimers were
      studied in two patients with thrombotic thrombocytopenic purpura (TTP) undergoing
      splenectomy because of refractoriness to plasma exchange. In both cases, a
      decrease in the largest normal vWf multimers was found at presentation. In one
      case, splenectomy resulted in a long-term remission and was followed by a normal
      multimeric pattern. In the other case, splenectomy failed to produce a remission
      and was followed by the appearance of ultralarge multimers, which disappeared-
      resulting in a normal pattern--when a sustained remission was achieved after
      vincristine infusion and further plasma exchanges. These results suggest that
      splenectomy per se has no consistent effect on the vWf multimeric structure in
      TTP patients, and provide further evidence on the good prognostic value of the
      achievement of a normal multimeric pattern in these patients.

PMID- 8292729
TI  - Arg578Gln mutations in the von Willebrand factor gene in three unrelated cases of
      type IIB von Willebrand disease.
AB  - A recurrent heterozygous CGG-->CAG (Arg578Gln) mutation was detected in exon 28
      of the von Willebrand factor gene in three additional unrelated families with
      inherited type IIB von Willebrand disease. This identical mutation showed a
      differential phenotypic expression in each family.

PMID- 8292730
TI  - Genetic mutations in ten unrelated American patients with symptomatic type 1
      protein C deficiency.
AB  - Symptomatic patients with Type 1 protein C deficiency and venous thrombosis were
      analysed for defects in this gene using polymerase chain reaction amplification
      and direct sequencing of all nine exons. Ten different heterozygous point
      mutations were detected in 19 patients from eleven American families. Seven
      represent novel mutations. Two of these were found in the TATA box or near the
      transcription initiation site and presumably lead to loss of transcription, and
      seven missense mutations were found including G103R, P168L, R169W, I201T, P279L,
      T298M, and C384Y. These may lead to abnormal folding or thermodynamic instability
      of the protein C molecule, potentially causing abnormal secretion or rapid
      clearance from the circulation. Two other protein C mutations, a nonsense
      mutation at codon Trp-145 and a deletion inducing a frameshift at codon 364
      resulting in premature termination at codon 378, likely lead to unstable
      products. The previously published R169W mutation resulted in a Type 1
      deficiency. The data show that diverse molecular defects result in similar
      phenotypes and emphasize that a wide variety of mutations are responsible for
      Type 1 protein C deficiency in the American setting of a diverse population.

PMID- 8292731
TI  - Experimental hypothyroidism increases plasminogen activator inhibitor activity in
      rat plasma.
AB  - The aim of the present study was to investigate whether hypothyroidism would
      affect the components of the rat plasma fibrinolytic system. Hypothyroidism was
      induced by feeding rats a thiouracil-containing diet for 2 weeks. During this
      period, half of the animals received subcutaneous injections of L-thyroxine (20
      micrograms/kg daily) to restore thyroid hormone levels. Groups of euthyroid rats
      were similarly treated with L-thyroxine. Plasma tissue-type PA (t-PA) activity
      was not affected by thyroid status. Plasma urokinase-type PA (u-PA) activity was
      significantly decreased by the thiouracil-containing diet; however, this effect
      was not abolished by L-thyroxine. Plasminogen, alpha 2-antiplasmin and fibrinogen
      were not affected by hypothyroidism. In the hypothyroid group, plasma PAI
      activity was significantly increased; no such increase was found in animals
      simultaneously receiving L-thyroxine. Plasma PAI activity correlated with T3 (r =
      -0.586; P < 0.005) and cholesterol (r = +0.737; P < 0.001); in multiple
      regression analysis, however, the correlation between PAI activity and T3 was not
      significant. The increase in plasma PAI activity during hypothyroidism may thus
      not be a direct effect of the thyroid hormone, but an indirect one through some
      other, possibly cholesterol related, component.

PMID- 8292732
TI  - A low volume specimen container suitable for monitoring the aPTT of heparinized
      patients.
AB  - Differences in the activated partial thromboplastin time (aPTT) were shown when
      blood taken from patients receiving intravenous heparin therapy was collected
      into 5 ml and 1 ml citrate containers. Mean aPTTs were 27% shorter with the
      plasma from the 1 ml citrate containers (n = 23). These results were paralleled
      by a 37% reduction in the mean heparin concentration (n = 11) and a 77% increase
      in the mean platelet factor 4 (PF4) concentration (n = 7). This phenomenon is due
      to increased platelet activation and subsequent increased heparin neutralization
      in the 1 ml citrate container. In an attempt to overcome this, the citrate was
      removed from a 1 ml container and replaced with a buffered tri-sodium citrate
      solution containing theophylline, adenosine and dipyridamole anticoagulant
      (CTAD). Blood from heparinized patients taken into both 5 ml citrate and 1 ml
      CTAD showed a correction of the shortening artefact in the low volume container.
      The mean aPTT of plasmas from the 1 ml CTAD container showed an increase of 10%
      compared with the 5 ml citrate. There was no significant difference in the mean
      heparin or PF4 concentrations of blood taken into either container. The 1 ml CTAD
      tube described is a suitable collection container for monitoring heparin in
      neonates or patients who are difficult to venepuncture and overcomes the
      neutralization of heparin in part filled low volume containers.

PMID- 8292733
TI  - Are oral contraceptives a more important risk factor than pregnancy in women with
      congenital antithrombin III deficiency?

PMID- 8292734
TI  - When good enzymes go bad: conversion of topoisomerase II to a cellular toxin by
      antineoplastic drugs.

PMID- 8292735
TI  - Transfer of arsenite from glutathione to dithiols: a model of interaction.
AB  - The interactions of arsenate and arsenite with meso-2,3-dimercaptosuccinic acid
      (DMSA) have been characterized using carbon-13 nuclear magnetic resonance. These
      studies show that DMSA reduces arsenate to arsenite and complexes arsenite.
      Monitoring the carbon-13 signals of complexed DMSA and liberated glutathione
      shows that DMSA readily extracts arsenite from a (glutathione)3-arsenite complex,
      proving the affinity of arsenite for dithiols is greater than that for
      monothiols. Competition between DMSA (vicinal thiols) and dithioerythritol (1,4
      dimercapto-2,3-butanediol) for binding of arsenite indicates that the binding
      affinity is inversely related to the distance between the two thiol groups. On
      the basis of these findings, a model for the interaction of arsenic with mono-
      and dithiol-containing molecules is proposed.

PMID- 8292736
TI  - Synthesis of 3-nitrobenzo[a]pyrene bay-region trans-7,8-diol anti-9,10-epoxide
      and the corresponding N2-deoxyguanosine adduct.
AB  - 3-Nitrobenzo[a]pyrene (3-nitro-BaP) is a potent mutagenic environmental
      contaminant, and its biological activities have been intensively studied. It is
      significant to prepare its reactive metabolites and the corresponding modified
      DNA adducts for biological studies. The synthesis of its oxidized proximate
      metabolite trans-7,8-dihydro-3-nitrobenzo[a]pyrene (3-nitro-BaP-trans-7,8
      dihydrodiol, 1), its oxidized ultimate metabolite trans-7,8-dihydroxy-anti-9,10
      epoxy-7,8,9,10-tetrahydro-3- nitrobenzo[a]pyrene (3-nitro-BaP-DE, 2), and the
      corresponding DNA adduct 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,10
      tetrahydro-3- nitrobenzo[a]pyrene is described.

PMID- 8292737
TI  - Serum antibodies from halothane hepatitis patients react with the rat endoplasmic
      reticulum protein ERp72.
AB  - Immunoblotting studies have previously shown that serum antibodies from halothane
      hepatitis patients react with several liver microsomal proteins that have been
      modified by the trifluoroacetyl halide metabolite of halothane. In this study, an
      80-kDa protein recognized by the patients' antibodies has been purified from rat
      liver microsomes and characterized. When the purified trifluoroacetylated 80-kDa
      and native 80-kDa proteins were employed as test antigens in an enzyme-linked
      immunosorbent assay, serum antibodies from halothane hepatitis patients reacted
      with both of these proteins to a significantly greater extent than did serum
      antibodies from control patients. Amino acid sequence analyses of several
      hydrolytic peptide fragments of the 80-kDa protein showed that the protein was
      99% identical to the deduced amino acid sequence of a murine cDNA of the luminal
      endoplasmic reticulum protein ERp72. These results indicate that
      trifluoroacetylated ERp72 in the liver of halothane hepatitis patients may induce
      immune responses against epitopes present on the covalently altered protein and
      those present on the native protein and may have a role in halothane hepatitis.
      In addition, immunoblot and immunohistochemical studies revealed that the 80-kDa
      protein was present in all tissues studied, but was in highest concentration in
      liver, adipose tissue, ovaries, and testes and was enriched in specific cells of
      some organs. In the future, these findings should help define the physiological
      function of ERp72.

PMID- 8292738
TI  - Unwinding and hydrodynamic flow linear dichroism characteristics of supercoiled
      DNA covalently modified with two isomeric methylchrysene diol epoxides of
      different biological activities.
AB  - Adducts derived from the covalent binding of two positional monomethyl
      substituted isomers of a bay region chrysene diol epoxide to supercoiled pIBI30
      DNA (2926 base pairs/genome) were prepared, and their characteristics were
      investigated by a combination of gel electrophoresis and flow linear dichroism
      techniques. The 5- and 6-methyl derivatives of trans-1,2-dihydroxy-anti-3,4-epoxy
      1,2,3,4-tetrahydrochrysene [(+)-5- and (+)-6-MeCDE, respectively], both with
      1R,2S,3S,4R stereochemistry, are characterized by significant differences in
      their biological activities [Melikian et al. (1988) Cancer Res. 48, 1781-1787].
      When covalently bound to plasmid DNA, these two molecules give rise to striking
      differences in the gel electrophoretic and flow hydrodynamic characteristics of
      the modified supercoiled DNA. The hydrodynamic flow linear dichroism of
      linearized DNA molecules (obtained by EcoRI enzyme digestion of covalently closed
      supercoiled pIBI30 DNA), modified covalently with the highly tumorigenic and
      mutagenic (+)-5-MeCDE derivative, indicates that flexible joints, bends, or kinks
      are formed at the site of binding of (+)-5-MeCDE. Slab gel data, as well as
      ethidium bromide-titration tube agarose gel electrophoresis data, indicate that
      the formation of (+)-5-MeCDE-DNA lesions causes the removal of superhelical turns
      with an unwinding angle of 13 +/- 3 degrees per covalently bound polycyclic
      aromatic residue. In contrast, the biological inactive (+)-6-MeCDE does not
      significantly alter the characteristics of supercoiled DNA, the unwinding angle
      is only 2.7 +/- 1 degrees, and the changes in persistence lengths detected by the
      flow linear dichroism technique are significantly smaller than in the case of (+)
      5-MeCDE-DNA adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292739
TI  - Quantitation of base substitutions and deletions induced by chemical mutagens
      during DNA synthesis in vitro.
AB  - An experimental system has been developed by which base substitutions and
      frameshift deletions can be quantitated in vitro, using two-phase 20%
      polyacrylamide gel electrophoresis. Oligodeoxynucleotides, modified site
      specifically, were used as templates in primer extension reactions catalyzed by
      DNA polymerase alpha, polymerase beta, and the Klenow fragment of Escherichia
      coli DNA polymerase I, with and without 3'-->5' exonuclease activity. Lesions
      studied included 7,8-dihydro-8-oxodeoxyguanosine, 7,8-dihydro-8
      oxodeoxyadenosine, O6-methyldeoxyguanosine, N-(deoxyguanosin-8-yl)-2
      (acetylamino)fluorene, and N-(deoxyguanosin-8-yl)-2- aminofluorene. Products of
      translesional synthesis contained dC, dA, dG, or dT opposite the lesion or one-
      and two-base deletions and were separated using a two-phase polyacrylamide gel
      system. When a template containing 8-oxoguanine was used, dAMP and/or dCAMP was
      incorporated opposite the lesion, the relative amounts depending on the DNA
      polymerase used. In contrast, the nonmutagenic base, dTMP, was incorporated
      exclusively opposite 8-oxodA in reactions catalyzed by Klenow fragment and pol
      alpha. The improved resolution provided by the two-phase gel system revealed
      misincorporation of dGMP opposite 8-oxodA in reactions catalyzed by pol beta.
      dTMP and small amounts of dCMP were incorporated opposite the lesion on an O6MedG
      modified template. The bulky adduct, dG-C8-AAF, principally produced deletions;
      in contrast, dG-C8-AF promoted incorporation of dCMP, a nonmutagenic base. This
      experimental system should prove useful for establishing the miscoding potential
      of defined lesions in DNA templates and in correlating this information with the
      mutagenic properties of DNA adducts observed in cells.

PMID- 8292740
TI  - Slow-binding inhibition of carboxylesterase and other serine hydrolases by
      chlorodifluoroacetaldehyde.
AB  - The chlorofluorocarbon substitute 1,2-dichloro-1,1-difluoroethane (HCFC-132b)
      undergoes oxidative metabolism in rats to give a range of metabolites, including
      chlorodifluoroacetaldehyde [Harris and Anders (1991) Chem. Res. Toxicol. 4, 180].
      The present experiments were undertaken after studies to characterize an
      unidentified metabolite of HCFC-132b revealed that chlorodifluoroacetaldehyde was
      toxic in vivo: rats given chlorodifluoroacetaldehyde died showing signs of
      cholinergic stimulation. Because some fluoroketones are known inhibitors of
      hydrolases, including acetylcholinesterase, the inhibitory effects of
      chlorodifluoroacetaldehyde on acetylcholinesterase (electric eel and human
      erythrocyte), on pseudocholinesterase (horse serum), on carboxylesterase (pig
      liver), and on alpha-chymotrypsin (bovine pancreas) were studied. In aqueous
      solution, the ratio chlorodifluoroacetaldehyde:chlorodifluroacetaldehyde hydrate,
      as determined by 1H nuclear magnetic resonance spectroscopy, was 1:157.
      Chlorodifluoroacetaldehyde was a slow-binding inhibitor of both
      acetylcholinesterases, of pseudocholinesterase, and of carboxylesterase; the Ki
      values, corrected for the aldehyde:hydrate ratio, were 150 nM, 1.7 nM, 3.7 nM,
      and 23 pM, respectively, as determined by final velocity of the progress curves;
      the kon values were 9.1 x 10(4), 1.1 x 10(5), 3.2 x 10(4), and 9.2 x 10(5) M-1
      min-1, respectively. Chlorodifluoroacetaldehyde did not inhibit alpha
      chymotrypsin. Acetaldehyde and trichloroacetaldehyde were classical competitive
      inhibitors of acetylcholinesterase. These results show that
      hydrochlorofluorocarbon metabolites may exert significant biological effects.

PMID- 8292741
TI  - Formation of 1,N2- and N2,3-ethenoguanine from 2-halooxiranes: isotopic labeling
      studies and isolation of a hemiaminal derivative of N2-(2-oxoethyl)guanine.
AB  - Vinyl halides are oxidized to 2-halooxiranes, which rapidly rearrange to 2
      haloacetaldehydes. Both of these species can react with DNA to generate a variety
      of adducts, including the potentially mutagenic etheno (epsilon) products.
      Evidence was provided through kinetic studies that the epsilon-Gua adducts are
      formed primarily from 2-haloxiranes; consistent with this view, epoxide hydrolase
      inhibited the formation of N2,3-epsilon-Gua from vinyl chloride but alcohol
      dehydrogenase did not. Assignments of the NMR shifts of the etheno protons of
      1,N2- and N2,3-epsilon-Gua were made with the use of 15N labeling and nuclear
      Overhauser effects, in revision of the literature. The H-5 proton of N2,3-epsilon
      Gua showed facile exchange in acid or base; the H-7 proton of 1,N2-epsilon-Gua
      was exchanged at neutral or basic pH but not in acid. Reaction of Br2CHCH2OH
      (labeled at C1 with 2H or 13C) with Guo yielded 1,N2-epsilon-Gua and N2,3-epsilon
      Gua, presumably through the intermediacy of 2-bromooxirane. 1H NMR analysis
      indicated that the labeled carbon was attached to the original Guo N2 atom in
      both cases. When N2-(2-oxoethyl)Gua was generated from a diethyl acetal or from a
      glycol, the major product was the cyclic derivative 5,6,7,9-tetrahydro-7-hydroxy
      9-oxoimidazo[1,2-alpha]purine. This compound was also formed in considerable
      yield from the reaction of 2-chlorooxirane with Guo, dGuo 5'-phosphate, or DNA
      and is relatively stable in the presence of acid or mild base. It does not appear
      to be readily dehydrated to yield the etheno adducts but may be of significance
      as a DNA adducts in its own right.

PMID- 8292742
TI  - Isoform-selective mechanism-based inhibition of human cytochrome P450 1A2 by
      furafylline.
AB  - Biotransformation reactions catalyzed by human cytochrome P450 1A2 (P450 1A2)
      appear to play a significant role in both the metabolic clearance of drugs and
      the activation of environmental contaminants and drugs to toxic or carcinogenic
      species. Furafylline is a potent and selective inhibitor of P450 1A2 activity in
      human liver microsomes [Sesardic, D., Boobis, A., Murray, B., Murray, S., Segura,
      J., De La Torre, R., and Davies, D. (1990) Br. J. Clin. Pharmacol. 29, 651-663]
      which may be of great utility in defining the role of P450 1A2 in metabolic
      processes. We have investigated the hypothesis that furafylline is a mechanism
      based inhibitor of P450 1A2. Key findings consistent with this hypothesis are the
      following: (1) Furafylline causes a time- and cofactor-dependent loss of P450 1A2
      activity which does not return upon dialysis. (2) The loss of activity is
      associated with a reduction of P450 spectral content which is in turn
      proportional in amount to P450 1A2-associated catalytic activity in uninhibited
      microsomes from 7 individual livers. (3) The inactivation of P450 1A2 is
      characterized by a Ki of 23 microM, a kinact of 0.87 min-1 and a furafylline
      depletion-based partition ratio of approximately 3-6 metabolic events per
      inactivating event. (4) The processing of the C-8 methyl group of furaylline is
      involved in inactivation as demonstrated by the observation of a deuterium
      isotope effect of approximately 2.0 on kinact and no effect on Ki when the C-8
      methyl group protons of furafylline are replaced with deuterium atoms.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8292743
TI  - Synthesis of 1- and 3-fluorobenzo[a]pyrene.
AB  - Fluoro-substituted aromatic hydrocarbons are useful probes for studying
      mechanistic details of oxygen transfer in metabolism catalyzed by cytochrome
      P450. Benzo[a]pyrene (BP) is a particularly suitable substrate for investigating
      this mechanism. Because 3-hydroxybenzo[a]-pyrene is one of the major metabolites
      of BP, preparation of 3-fluorobenzo[a]pyrene (3-FBP) was undertaken. Synthesis of
      3-FBP was achieved in five steps starting from 6-chlorobenzo[a]pyrene (6-ClBP).
      In this synthesis 1-FBP was also produced. The overall yield was 16% for both 1
      FBP and 3-FBP. After nitration of 6-ClBP at C-1 and C-3 with N2O4 and reduction
      by SnCl2 to the amino group, diazotization with NaNO2 in the presence of NaBF4
      followed. The diazonium tetrafluoroborate salts were reacted with (CH3)2NH to
      produce the dimethyltriazonium tetrafluoroborate salts. By heating in toluene, a
      mixture of 1-F-6-ClBP and 3-F-6-ClBP was obtained. The two isomers were separated
      by normal-phase medium-pressure liquid chromatography. The chloro substituent was
      then selectively removed from both isomers by hydrogenolysis to yield 1-FBP and 3
      FBP.

PMID- 8292744
TI  - Fatty acid beta-oxidation-dependent bioactivation of halogenated thiaalkanoic
      acids in isolated rat hepatocytes.
AB  - 5,6-Dichloro-4-thia-5-hexenoic acid (DCTH), the desamino analog of the
      nephrotoxic cysteine S-conjugate S-(1,2-dichlorovinyl)-L-cysteine, is toxic to
      liver and kidney mitochondria. The mechanism by which DCTH produces mitochondrial
      dysfunction has not been defined. The objective of the present experiments was to
      test the hypothesis that DCTH is bioactivated by the mitochondrial fatty acid
      beta-oxidation system to cytotoxic intermediates. Incubation of isolated rat
      hepatocytes with DCTH produced a time- and concentration-dependent decrease in
      cell viability. The even-chain, elongated analog 7,8-dichloro-6-thia-7-octenoic
      acid was also cytotoxic, whereas the odd-chain-length analogs 6,7-dichloro-5-thia
      6-heptenoic acid and 8,9-dichloro-7-thia-8-nonenoic acid were not. Sodium
      benzoate reduced the cytotoxicity of DCTH, indicating a role for coenzyme A in
      the bioactivation of DCTH. DCTH decreased cellular ATP concentrations, the
      cellular energy charge, and cellular glutathione concentrations; these changes
      preceded the decrease in cell viability, indicating that mitochondrial
      dysfunction may be an early event in DCTH-induced cytotoxicity. 6-Chloro-5,5,6
      trifluoro-4-thiahexanoic acid and 5,6,7,8,8-pentachloro-4-thia-5,7-octadienoic
      acid were also cytotoxic in isolated hepatocytes, whereas 4-(2-benzothiazolyl)-4
      thiabutanoic acid was not. These data are consistent with the hypothesis that the
      mitochondrial fatty acid beta-oxidation system is involved in the bioactivation
      of DCTH and that mitochondria may be important cellular targets in DCTH-induced
      cytotoxicity.

PMID- 8292745
TI  - Chloroperoxidase-mediated oxidation of 1,3-butadiene to 3-butenal, a
      crotonaldehyde precursor.
AB  - Previously, we have shown that 1,3-butadiene, a rodent and possibly a human
      carcinogen, can be oxidized by chloroperoxidase-H2O2 at pH 7.4 to yield the
      potent mutagens, butadiene monoxide and crotonaldehyde. Because the
      crotonaldehyde/butadiene monoxide ratio from reactions with chloroperoxidase was
      higher than that obtained from reactions with myeloperoxidase or cytochrome P450
      enzymes, in the present study, the chloroperoxidase reaction was further
      investigated in an attempt to define optimal conditions for catalysis and to
      possibly obtain direct evidence for the formation of the crotonaldehyde precursor
      3-butenal in these incubations. The results showed that butadiene monoxide and
      crotonaldehyde formation was optimal at pH 6.0. As opposed to incubations carried
      out at pH 7.4, GC analyses of incubations carried out at pH 4.5, 5.0, and 6.0
      demonstrated the presence of a new peak which had a retention time different from
      that of butadiene monoxide and crotonaldehyde. The new peak was identified as 3
      butenal by comparison of its retention time and mass spectrum with those of
      reference material. Evidence for 3-butenal being a precursor of crotonaldehyde
      was obtained by the findings that 3-butenal was not simply a decomposition
      product of butadiene monoxide or crotonaldehyde under the incubation or assay
      conditions, and that the 3-butenal/crotonaldehyde ratio decreased when the
      incubation time was increased between 5 and 30 min or when the incubation
      temperature was increased between 10 and 45 degrees C. The combined 3-butenal and
      crotonaldehyde concentrations remained constant at the various incubation
      temperatures. Furthermore, 3-butenal conversion to crotonaldehyde was faster at
      pH 7.4, compared to pH 6.0.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292746
TI  - Cytochrome P450-mediated oxidation of pentafluorophenol to
      tetrafluorobenzoquinone as the primary reaction product.
AB  - In the present study the oxidative dehalogenation of a para-halogenated phenol
      was studied using pentafluorophenol and its non-para-halogenated analogue 2,3,5,6
      tetrafluorophenol as model compounds. 19F NMR was used to characterize the
      metabolite patterns. In order to study the primary oxidation products of the
      microsomal cytochrome P450-catalyzed conversion, the alternative oxygen donors
      cumene hydroperoxide (CumOOH) and iodosobenzene (IOB) were used in addition to
      the use of NADPH and molecular oxygen. In a NADPH/oxygen-driven reaction, but
      also in a CumOOH- or IOB-driven cytochrome P450 reaction, tetrafluorophenol was
      converted to tetrafluorohydroquinone. However, for pentafluorophenol, the
      formation of tetrafluorohydroquinone as a product of its cytochrome P450-mediated
      conversion was only observed in the NADPH-driven system. Addition of reducing
      equivalents such as NADH to the CumOOH or IOB incubations resulted in the
      formation of tetrafluorohydroquinone. From these data it was concluded that the
      primary reaction product of the cytochrome P450-catalyzed conversion of
      pentafluorophenol is a reactive species that can be reduced to
      tetrafluorohydroquinone by NAD(P)H and, thus, must be tetrafluorobenzoquinone.
      Additional experiments with tetrafluorobenzoquinone, incubated in vitro with
      either microsomal protein or glutathione in the presence or absence of reducing
      equivalents, demonstrated that the tetrafluorobenzoquinone ends up bound to
      proteins, losing its fluorine atoms as fluoride anions. Thus, while cytochrome
      P450-mediated conversion of the 2,3,5,6-tetrafluorophenol results in the
      formation of tetrafluorohydroquinone as the primary reaction product,
      monooxygenation at a fluorinated para position, such as in pentafluorophenol,
      results in the formation of the reactive tetrafluorobenzoquinone derivative as
      the primary reaction product.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292747
TI  - Construction of Escherichia coli vectors containing deoxyadenosine and
      deoxyguanosine adducts from (+)-anti-dibenz[a,j]anthracene diol epoxide at a
      defined site.
AB  - Dibenz[a,j]anthracene (DB[a,j]A) is a carcinogenic polycylic aromatic
      hydrocarbon, which is metabolically activated through the formation of bay region
      diol epoxides. Site-specifically modified M13mp19-based vectors containing a
      single (+)-anti-dibenz[a,j] anthracene diol epoxide [(+)-anti-DB[a,j[A-DE]
      deoxyguanosine (dGuo) or -deoxyadenosine (dAdo) adduct were constructed. Four
      base oligonucleotides, 5'-HOTGCA-3' and 5'-HOCATG-3', corresponding to the
      central four base pairs in the PstI and SphI restriction endonuclease sites,
      respectively, in the multiple cloning region of M13mp19, were reacted in solution
      with (+/-)-anti-DB[a,j]A-DE. The resulting adducted oligonucleotides were
      separated and purified using reverse-phase HPLC. Several different singly
      adducted oligonucleotides were isolated, consisting of the various cis and trans
      addition products of the (+) and (-) enantiomers of the diol epoxide bound to
      dGuo or dAdo in the oligonucleotides. 5'-HOTGCA-3' containing the (+)-anti
      DB[a,j]A-trans-N2-dGuo adduct [T(DB[a,j]A-N2)GCA] and 5'-HOCATG-3' containing the
      (+)-anti-DB[a,j]A-trans-N6-dAdo adduct [C(DB[a,j]A-N6)ATG) were selected for
      subsequent ligation into M13mp19 vectors that had been constructed with a
      corresponding four base gap in the minus strand. Both unmodified and adducted
      oligonucleotides were successfully ligated into the M13mp19 vectors, [yields:
      unmodified -TGCA-M13mp19 (approximately 32%) and -CATG- M13mp19 (approximately
      42%); adducted T(DB[a,j]A-N2)GCA-M13mp19 (approximately 13%) and C(DB[a,j]A
      N6)ATG-M13mp19 (approximately 12%)]. The dAdo adduct-containing vector was
      characterized. The presence of a dAdo-DNA adduct at the recognition site of SphI
      inhibited restriction by SphI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292748
TI  - Base pairing of 8-oxoguanosine and 8-oxo-2'-deoxyguanosine with 2'
      deoxyadenosine, 2'-deoxycytosine, 2'-deoxyguanosine, and thymidine.
AB  - Base pair formation between O-silyl derivatives of 8-oxoguanosine (8-OxoG) and 8
      oxo-2'-deoxyguanosine (8-OxodG) with 2'-deoxyadenosine (dA), 2'-deoxycytosine
      (dC), 2'-deoxyguanosine (dG), and thymidine (dTHd) have been examined by NMR
      methods in chloroform. 8-OxoG and 8-OxodG form base pairs with all four
      nucleosides, suggesting that they can mimic the base pairing properties of any
      DNA base. In 8-OxodG.dA or 8-OxoG.dA base pairs both bases assume Hoogsteen
      geometry with respect to both bases. Hoogsteen and Watson-Crick base pairs are
      formed between 8-OxodG or 8-OxoG and either dThd or dG. Only Watson-Crick
      geometry is seen for 8-OxodG.dC and 8-OxoG.dC base pairs. In all base pairs the
      glycosidic bond of 8-OxodG or 8-OxoG is syn and anti for the base pair partner.
      Additional base pairing studies with the modified nucleosides 1-methyl-8
      oxoguanosine (1-Me-8-oxoG), 7-methyl-8-oxoguanosine (7-Me-8-oxoG), and 8
      methoxyguanosine (8-OMeG), modified nucleosides structurally related to 8-OxoG
      and 8-OxodG, support the proposed base pair structures and aided in the
      determination of base pair geometry. Association constants were determined for 8
      OxoG.dN and 8-OxodG.dN (N = A, C, G, Thd) base pairs as well as the normal dTHd-A
      and dG.dC base pairs. The magnitude of the association constants allows the
      relative stabilities of the base pairs to be determined: 8-OxodGWC.dC (8
      OxoGWC.dC) approximately dGWC.dC > 8-OxodGH.dG (8-OxoGH.dG) > 8-OxodGH.dA (8
      OxoGH.dA) > 8-OxodGH.dThd (8-oxoGH.dThd) approximately dThd.dA. The formation of
      these base pairs is consistent with the known mutagenic nature of 8-oxo-2'
      deoxyguanosine and with NMR studies of oligonucleotides containing the 8-oxoG
      modification.

PMID- 8292749
TI  - Energetics of the metabolic production of (E,E)-muconaldehyde from benzene via
      the intermediates 2,3-epoxyoxepin and (Z,Z)- and (E,Z)-muconaldehyde: ab initio
      molecular orbital calculations.
AB  - To assess the feasibility of the pathway set out in the title, we have carried
      out ab initio molecular orbital calculations of the energies of cisoid- and
      transoid-2,3-epoxyoxepin and the eZzZz-, eZeZz-, eEeZz-, eEeEz-, and eEeEe
      conformers of muconaldehyde at the MP2/6-31G* (frozen core, valence orbitals
      active) level with full geometry optimization using the split-valence RHF/6-31G*
      basis set. Including thermal energies, derived from vibrational frequencies
      obtained at the RHF/6-31G*//RHF/6-31G* level, reaction energies (that would
      correspond to gas phase data at 298 K) have been evaluated. The muconaldehyde
      conformers are lower in energy than the epoxyoxepin, i.e., are formed
      exothermically, and in accord with experiment, the Z,Z-conformers are less stable
      than the E,Z, and the E,Z less stable than the E,E. In addition, we have
      characterized the transition state for the fission of the C-O bond in the epoxy
      ring and the C-O bond in the oxepin ring of transoid-2,3-epoxyoxepin, thereby
      generating (eZzZz)-muconaldehyde. With an activation energy of 16.5 kcal mol-1
      the half-life of the epoxyoxepin is very short at the temperatures employed in
      the experiments, less than 1 min, which explains why it has not been detected. To
      gain some insight into the isomerization about the carbon-carbon double bonds in
      the muconaldehyde conformers, we have examined the possible involvement of 2
      formyl-2H-pyran and cyclobutene-3,4-dicarboxaldehyde as intermediates. In model
      reactions simulating the microsomal monooxygenase system, the formation of
      benzene oxide and of the epoxyoxepin are found to be very favorable exothermic
      processes.

PMID- 8292750
TI  - Role of metallothionein in zinc(II) and chromium(III) mediated tolerance to
      carbon tetrachloride hepatotoxicity: evidence against a trichloromethyl radical
      scavenging mechanism.
AB  - The .CCl3 radical generated during the metabolism of CCl4 is readily spin trapped
      in vivo and in vitro by phenyl N-tert-butylnitrone (PBN) to form the stable
      PBN/.CCl3 radical adduct, which can then be extracted into organic solvents and
      detected by ESR spectroscopy. We have used this technique to examine the proposed
      protective roles of Zn(II), Cr(III), and metallothionein (MT) against carbon
      tetrachloride toxicity in vivo. Hepatic MT, which is induced by Zn(II), has been
      proposed to protect against CCl4-induced cellular damage by scavenging the free
      radical metabolites formed. CCl4-induced hepatotoxicity was significantly
      suppressed in male Sprague-Dawley rats pretreated with a single dose of 5 mg/kg
      Zn(II) or Cr(III) according to standard serum assays for liver-specific enzymes,
      and hepatic MT was elevated after pretreatment with either Zn(II) or Cr(III). In
      vitro, no difference was detected in either the amount of CCl4-derived free
      radical metabolites formed or the rate at which they were formed by microsomes
      from rats pretreated 24 h in advance with 5 mg/kg Zn(II) or Cr(III). Extraction
      of rat liver with 2:1 chloroform/methanol 1 h after the administration of a 0.8
      mL/kg intraperitoneal or intragastric dose of CCl4 also revealed no difference in
      the amount of trichloromethyl radical spin trapped in vivo following pretreatment
      with either Zn(II) or Cr(III). These results suggest that pretreatment with
      either Zn(II) or Cr(III) does not affect CCl4 metabolism nor does the MT
      significantly scavenge the trichloromethyl free radical metabolite.

PMID- 8292751
TI  - Synthesis, absolute configuration, and analysis of malathion, malaoxon, and
      isomalathion enantiomers.
AB  - Syntheses of the enantiomers of malathion, malaoxon, and isomalathion are
      reported herein. Malathion enantiomers were prepared from (R)- or (S)-malic acid
      in three steps. Enantiomers of malathion were converted to the corresponding
      enantiomers of malaoxon in 52% yield by oxidation with monoperoxyphthalic acid,
      magnesium salt. The four isomalathion stereoisomers were prepared via two
      independent pathways using strychnine to resolve the asymmetric phosphorus
      moiety. The absolute configurations of the four stereoisomers of isomalathion
      were determined by X-ray crystallographic analysis of an alkaloid salt precursor.
      A high-performance liquid chromatography technique was developed to resolve the
      four stereoisomers of isomalathion, and to determine their stereoisomeric ratios.

PMID- 8292752
TI  - Interaction of acetylcholinesterase with the enantiomers of malaoxon and
      isomalathion.
AB  - The biomolecular reaction constants (ki), dissociation constants (Kd), and
      phosphorylation constants (kp) were determined for the enantiomers of malaoxon
      against rat brain acetylcholinesterase, and for the stereoisomers of isomalathion
      against rat brain acetylcholinesterase and electric eel acetylcholinesterase. (R)
      Malaoxon was an 8.6-fold more potent anti-cholinesterase than (S)-malaoxon.
      Isomalathion stereoisomers with the R configuration at carbon were 3-13-fold
      stronger inhibitors than those with the S configuration. The isomalathion
      stereoisomers with the R configuration at phosphorus were 4.3-8.8-fold stronger
      inhibitors of rat brain acetylcholinesterase, yet 3.4-5.8-fold weaker inhibitors
      of electric eel acetylcholinesterase, than the isomalathion stereoisomers with
      the S configuration at phosphorus. The rat brain acetylcholinesterase spontaneous
      (k0 = approximately 13.0 x 10(-3) min-1) and oxime-mediated (koxime) = 51.0 x 10(
      3) min-1) reactivation rate constants following inhibition by isomalathion
      stereoisomers with the R configuration at phosphorus were comparable to
      spontaneous (11.3 x 10(-3) min-1) and oxime-mediated (50.2 x 10(-3) min-1)
      reactivation rates obtained for (S)-isoparathion methyl. These data support a
      common phosphorylation mechanism, namely, the displacement of the thiosuccinyl
      moiety from isomalathion stereoisomers with the R configuration at phosphorus,
      and displacement of the p-nitrophenoxy ligand from (S)-isoparathion methyl to
      form the same O,S-dimethyl phosphorothiolated enzyme. Rat brain
      acetylcholinesterase inhibited by the isomalathion stereoisomers with the S
      configuration at phosphorus were refractory to reactivation, suggesting an
      alternate mechanism of inhibition, i.e., the loss of the methylthio ligand.
      Several mechanisms are proposed to account for the subsequent
      nonreactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292753
TI  - Role of quinone methide in the in vitro toxicity of the skin tumor promoter
      butylated hydroxytoluene hydroperoxide.
AB  - An electrophilic quinone methide (2,6-di-tert-butyl-4-methylene-2,5
      cyclohexadienone, BHT-QM) functions in the toxicity of butylated hydroxytoluene
      (BHT) in both rodent liver and lung. BHT-QM has also been demonstrated to mediate
      tumor promotion in mouse skin by another metabolite of BHT, 2,6-di-tert-butyl-4
      hydroperoxy-4-methyl-2,5-cyclohexadienone (BHTOOH). In the present study, the
      role of BHT-QM in the cytotoxicity of BHTOOH was investigated. The toxicity of
      BHTOOH was potentiated by glutathione depletion and inhibited by thiol compounds,
      indicating that BHTOOH is activated to a thiol-reactive, toxic intermediate. This
      activation process was suggested to be iron-dependent by the ability of an
      Fe(III)-specific chelator to inhibit BHTOOH toxicity. Comparative study of
      analogs of BHTOOH in which the 4-methyl group was substituted with CD3, ethyl,
      isopropyl or tert-butyl supported the hypothesis that BHT-QM mediates this
      toxicological response. The decreased rate of reactivity of quinone methides that
      occurs as the 4-alkyl group is enlarged was accompanied by a corresponding
      reduction in toxic potency. The structural requirements for quinone methide
      toxicity were also explored with a series of BHTOOH analogs substituted at the 2-
      and 6-positions of the molecule. Reducing the lipophilicity of the 2,6-tert-butyl
      groups is known to increase quinone methide reactivity with glutathione but does
      not diminish the rate of quinone methide formation from the hydroperoxide.
      Interestingly, alteration of only one of the tert-butyl groups did not change the
      toxic potency, whereas removal or replacement of both tert-butyl groups
      dramatically reduced the toxicity in control cells but not glutathione-depleted
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292754
TI  - Profile of transition homes/shelters for victims of family violence.
AB  - This article presents the results of the Transition Home Survey--Supplement to
      the Residential Care Facilities Survey (RCF) 1991/92. The RCF is an annual survey
      sponsored by Statistics Canada. The Transition Home Survey was the first national
      endeavour to gather detailed information on clients and services provided in
      transition homes for victims of family violence. The target universe consisted of
      facilities defined as 'transition homes', which include shelters, second stage
      housing, family resource centres, safe home networks, satellites, emergency
      shelters and other homes for victims of family violence. The data presented
      covers four topics--facilities, services, caseload and revenue and expenditures.

PMID- 8292755
TI  - Social status and health risks in Canadian adults: 1985 and 1991.
AB  - Smoking, overweight and physical inactivity are three lifestyle risk factors
      associated with increased risks of cancer, heart disease and other chronic
      diseases. Using data from the 1985 and 1991 General Social Surveys, this study
      examines the prevalence of these risk factors by respondents' education levels,
      and how the prevalence of these risk factors changed from 1985 to 1991. The
      prevalence of smoking, overweight and physical inactivity varied widely by
      respondent's education levels. In 1991, persons with more education had
      consistently lower rates for all three risk factors than those with lower
      educational levels. Smoking and sedentary living declined between 1985 and 1991,
      but the prevalence of overweight increased. However, except for physical
      activity, little progress was made in narrowing the socio-economic differences
      for these risks. Declines in the prevalence of health risks varied by educational
      level and by sex within educational level. This has implications for future
      patterns of chronic disease morbidity and mortality. Differences in risk factor
      prevalence between socioeconomic groups may be partly due to differences in how
      each group acquires and interprets health information, and to differences between
      groups' exposure to environments that support healthy lifestyles.

PMID- 8292756
TI  - Use of postal codes and addresses in the analysis of health data.
AB  - This article describes various ways of using postal codes and addresses to
      analyze health data. It gives examples of files that contain data suitable for
      coding to small areas, explains how the coding can be done efficiently using the
      Postal Code Conversion File (PCCF), and shows various ways of analyzing the
      resulting data. It also points out limitations of the data and methods, and
      suggests ways of avoiding or working around some of the problems frequently
      encountered. Examples are given of several types of analytical studies based on
      data coded to local area through use of postal codes and addresses. Examples are
      also given of simpler types of analysis not requiring recourse to the PCCF, which
      are based on only the first three characters of the postal code.

PMID- 8292757
TI  - How far is it to the nearest hospital? Calculating distances using the Statistics
      Canada Postal Code Conversion File.
AB  - This report demonstrates how to calculate distances between points described in
      terms of latitude and longitude, using the Postal Code Conversion File (PCCF) and
      other files available from the Geography Division of Statistics Canada. Examples
      based on hospital data show how the results can be summarized in the form of
      tables, figures, or maps. Aerial distance to the nearest hospital is a crude but
      objective indicator of geographic accessibility to hospital services. Distances
      were calculated between enumeration area centroids for the population and
      blockface or enumeration area centroids for the hospitals. The median aerial
      distance to the nearest hospital facility in Canada was less than 3 km, while the
      mean distance was about 6 km. For teaching hospitals, the median aerial distance
      was a little less than 30 km, while the mean distance was a little more than 90
      km. As most health files for administrative and research purposes contain postal
      codes, these techniques have potentially wide application.

PMID- 8292758
TI  - Adult Day Care centres in British Columbia: models, characteristics and services.
AB  - Adult Day Care (ADC) is increasingly being recognized as an important sub-system
      of the continuing care system. This paper reviews models developed in the United
      States and Britain and compares them, and the services they offer, with centres
      in British Columbia, Canada. Data on British Columbia are from a study in which
      all 49 centres in the province provided detailed information about their
      staffing, operating characteristics, activities and services. The study found
      B.C. compared favourably in providing services needed by ADC clients. Key
      differences between the B.C. centres and those in the U.S. and U.K. were: a
      larger proportion of B.C. centres were not affiliated with any other
      organization; B.C. centres admitted a range of clients and were less likely to
      cater exclusively to special needs groups; and, B.C. centres were more likely
      than centres in the U.S. to provide a number of services such as: dental care,
      transportation, bathing and physiotherapy.

PMID- 8292759
TI  - Births in Canada, 1991.

PMID- 8292760
TI  - Causes of death 1991.

PMID- 8292761
TI  - Deaths in Canada, 1991.

PMID- 8292762
TI  - Marriages in Canada, 1991.

PMID- 8292763
TI  - Nursing in Canada: registered nurses, 1992.

PMID- 8292764
TI  - Selected Mortality Statistics, Canada, 1921-1990.

PMID- 8292765
TI  - Therapeutic abortions in Canada, 1991.

PMID- 8292766
TI  - Scales for mental state and daily living activities for the elderly: clinical
      behavioral scales for assessing demented patients.
AB  - In the diagnosis, treatment, and care of dementia patients in the senile stage,
      comprehensive evaluation of ability in daily life and mental function is needed.
      Using a simple behavioral rating scale for the mental states (NM scale) and
      activities of daily living (N-ADL) of the elderly, we evaluated 250 elderly
      subjects. According to the NM scale, the scores for subjects in whom the severity
      was clinically diagnosed were as follows: normal, 50-48; borderline, 47-43; mild
      dementia, 42-31; moderate dementia, 30-17; and severe dementia, 16-0. Screening
      for dementia and determining its severity were readily accomplished using the NM
      scale, and basic activities in the daily life of the elderly could be evaluated
      effectively using the N-ADL. There was a significant correlation (r = 0.863)
      between the Hasegawa dementia scale and the NM scale (p < 0.001), a significant
      correlation (r = -0.947) between intellectual function scores of the GBS scale
      and the NM scale, and a significant correlation (r = 0.944) between motor
      function score of the GBS scale and the N-ADL score. Evaluations of daily life
      activities can be made not only by psychiatrists and clinical psychologists, but
      by nonspecialists as well, because they are based on data obtained by observation
      of daily life behaviors; thus, assessment is appropriate both in clinical
      settings and in places of living.

PMID- 8292767
TI  - Cognitive decline in Alzheimer's disease: elaborating on the nature of the
      longitudinal factor structure of the Mini-Mental State Examination.
AB  - The purpose of this paper was to use the Wechsler Adult Intelligence Scale (WAIS)
      to further define the nature of the underlying factors of the Mini-Mental State
      Examination (MMSE) as proposed by Tinklenberg et al. (1990). The MMSE was
      administered to 51 patients once every 6 months for at least one year; the WAIS
      was administered only at the beginning of the study. Stepwise regression analyses
      yielded these results: for the Following Commands factor, the best correlate was
      the Comprehension subtest; for the Language Repetition factor, the best correlate
      was the Picture Arrangement subtest; and for the Language Expression factor, the
      best correlates were the Digit Symbol and Object Assembly subtests. These
      relations help clarify the correlates of decline of AD patients on the MMSE.

PMID- 8292768
TI  - A cross-national self-report measure of depressive symptomatology.
AB  - The Center for Epidemiological Studies Depression scale (CES-D) was administered
      in Swedish to two representative samples, one aged 84 to 90 (mean = 87), the
      second aged 29 to 95 (mean = 61). There were both linear and quadratic
      differences with age: the oldest individuals were highest on depressive symptoms,
      but younger adults were higher than middle-aged. Dimensions or subscales
      identified by previous studies were generally replicated, including a sadness and
      depressed mood factor, a psychomotor retardation and loss of energy factor, and a
      well-being factor (on which items are reverse-scored to indicate depression). The
      findings support cross-national use of the CES-D to assess self-reported symptoms
      of depression in adults and older adults.

PMID- 8292769
TI  - Physical health and cognitive ability among married long-term-care patients and
      among their spouses--a comparison between home care and nursing home care.
AB  - The purpose of this study was to establish whether physical health and cognitive
      function in married long-term patients or in their spouses determines why some
      patients are cared for in home care while others reside in nursing homes. Out of
      38 married couples with a sick spouse cared for in a nursing home, 23 couples
      were studied; out of 34 couples with a sick spouse cared for in home care, 22
      patients and 25 spouses were studied. The results showed no significant
      differences in physical health score either between the two groups of patients,
      or between the two groups of spouses. Both home-care patients and nursing home
      patients had low cognitive function scores, but nursing home patients had
      significantly lower scores. A multivariate analysis showed that physical health
      and cognitive function explained only 20% of patients' residence. Between the two
      groups of spouses there was no difference in cognitive function score. The
      conclusion is that physical health status and cognitive function explain only to
      a small extent why married long-term care patients are cared for in nursing homes
      or in home care.

PMID- 8292770
TI  - Can changes in ward routines affect the severity of dementia? A controlled
      prospective study.
AB  - An extensive new caring program--including the introduction of Individual Care
      Plans and changes in ward organization, caring techniques, and caring philosophy-
      was introduced at two psychogeriatric wards with severely demented patients. The
      hypotheses were that the patients (n = 31) would improve in psychosocial capacity
      and orientation and the staff work load would decline in contrast to two other
      wards with a similar clientele (n = 31). After ten months the milieu was more
      "homelike," routines were more flexible, and the staff communicated more with the
      patients. However, the hypotheses were not proven. All patients in both groups
      deteriorated in ADL capacity, orientation, and behavior. The patients in the
      program wards became significantly more restless and disoriented and ate less
      than the patients in the contrast wards. The conclusion is that, despite optimal
      care, a humanistic approach, and support from staff, the progression of dementia
      symptoms is inevitable.

PMID- 8292771
TI  - Sexual activity and sex hormone levels in aging men.
AB  - A cross-sectional study of 60 men aged 65-80 was carried out to test the impact
      of the aging process on sexual hormones (testosterone, FSH, LH, prolactin),
      sexual activity, and the relations between them. Blood samples for hormone assays
      were taken between 8-9 A.M. in the primary care clinic at which the participants
      were registered. Data on sexual activity (coitus), sexual desire (libido),
      marital status, and age were obtained from the respondents by means of a
      structured interview. No relationship was found between testosterone (T) or
      prolactin (PL) and sexual activity. Nevertheless, a statistically significant
      relationship between FSH and LH versus age, and an inverse relationship between
      sexual activity and age were found. Hypogonadism (T level less than 3ng/ml) with
      normal levels of FSH and LH was observed in 11 respondents.

PMID- 8292772
TI  - Psychiatric manifestations of Pick's disease.
AB  - Pick's disease is a rare cause of dementia frequently misdiagnosed as Alzheimer's
      disease. Because patients with Pick's disease often present with psychiatric
      symptoms, the psychiatric aspects of this disorder are reviewed, as well as the
      pathology and epidemiology of the disease. Two case reports illustrate many of
      the clinical features of PD. A detailed examination of the psychiatric aspects of
      the disorder is followed by an elucidation of the many clinical differences
      between Pick's disease and Alzheimer's disease.

PMID- 8292773
TI  - Psychogeriatric outreach to rural families: the Iowa and Virginia models.
AB  - Elderly residents of rural areas are at significant risk for mental health
      problems, yet have less access to mental health services. Thus, most mental
      health problems among rural elderly remain either undiagnosed or untreated. We
      describe two models of mental health outreach programs to rural elderly in Iowa
      and Virginia, serving demographically, culturally, and epidemiologically
      different populations in geographically and economically dissimilar regions.
      Programs are compared on the basis of initiation, community partnerships, target
      population, target region, clinical disciplines involved, coordinating
      discipline, referral sources, operational model, initial home assessment, care
      planning, sustainability, cost, patient demographics, and primary and secondary
      diagnosed. Outreach programs are argued to be effective models of delivering
      services to geographically and/or socially isolated elderly populations. The
      experiences of our programs, though limited to rural populations, may be of
      relevance to any outreach program attempting to serve elderly presenting with or
      at risk for mental health problems.

PMID- 8292774
TI  - Care for the elderly: the role of the nursing home in the Dutch health care
      system.
AB  - Nursing homes, or verpleeghuizen, play an important role in the health care
      system in the Netherlands. These multifunctional institutions provide clinical
      and ambulatory (day hospital) care for somatic and psychogeriatric elderly with
      multiple pathology, disabilities, and handicaps. Quantitative data on morbidity,
      admission, and discharge of (psychogeriatric) nursing home patients are
      presented. The data on the nursing home institutions--number of residents, costs,
      and staff ratios--are placed in the context of the whole health care system. A
      new trend is to organize nursing home care in homes for the aged via substitution
      projects and dependences.

PMID- 8292775
TI  - Post-transcriptional regulation of nuclear-encoded genes in higher plants: the
      roles of mRNA stability and translation.

PMID- 8292776
TI  - Analysis of chloroplast transit peptide function using mutations in the carboxyl
      terminal region.
AB  - Protein import into chloroplasts requires a transit peptide, which interacts with
      the chloroplast transport apparatus and leads to translocation of the protein
      across the chloroplast envelope. While the amino acid sequences of many transit
      peptides are known, functional domains have been difficult to identify. Previous
      studies suggest that the carboxyl terminus of the transit peptide for ribulose
      bisphosphate carboxylase small subunit is important for both translocation across
      the chloroplast envelope and proper processing of the precursor protein. We
      dissected this region using in vitro mutagenesis, creating a set of mutants with
      small changes in primary structure predicted to cause alterations in secondary
      structure. The import behavior of the mutant proteins was assessed using isolated
      chloroplasts. Our results show that removal of a conserved arginine residue in
      this region results in impaired processing, but does not necessarily affect
      import rates. In contrast, substituting amino acids with low reverse turn or
      amphiphilic potential for other original residues affected import rate but not
      processing.

PMID- 8292777
TI  - Analysis of an osmotically regulated pathogenesis-related osmotin gene promoter.
AB  - Osmotin is a small (24 kDa), basic, pathogenesis-related protein, that
      accumulates during adaptation of tobacco (Nicotiana tabacum) cells to osmotic
      stress. There are more than 10 inducers that activate the osmotin gene in various
      plant tissues. The osmotin promoter contains several sequences bearing a high
      degree of similarity to ABRE, as-1 and E-8 cis element sequences. Gel retardation
      studies indicated the presence of at least two regions in the osmotin promoter
      that show specific interactions with nuclear factors isolated from cultured cells
      or leaves. The abundance of these binding factors increased in response to salt,
      ABA and ethylene. Nuclear factors protected a 35 bp sequence of the promoter from
      DNase I digestion. Different 5' deletions of the osmotin promoter cloned into a
      promoter-less GUSNOS plasmid (pBI 201) were used in transient expression studies
      with a Biolistic gun. The transient expression studies revealed the presence of
      three distinct regions in the osmotin promoter. The promoter sequence from -108
      to -248 bp is absolutely required for reporter gene activity, followed by a long
      stretch (up to -1052) of enhancer-like sequence and then a sequence upstream of 
      1052, which appears to contain negative elements. The responses to ABA, ethylene,
      salt, desiccation and wounding appear to be associated with the -248 bp sequence
      of the promoter. This region also contains a putative ABRE (CACTGTG) core
      element. Activation of the osmotin gene by various inducers is discussed in view
      of antifungal activity of the osmotin protein.

PMID- 8292778
TI  - Localization of light-inducible and tissue-specific regions of the spinach
      ribulose bisphosphate carboxylase/oxygenase (rubisco) activase promoter in
      transgenic tobacco plants.
AB  - Deletions in the spinach rubisco activase (Rca) promoter in transgenic tobacco
      were analyzed to define the regions necessary for conferring light-inducible and
      tissue-specific expression. Transgenic plants were constructed with Bal 31
      deletions of the Rca promoter fused to the coding region of the bacterial
      reporter gene beta-glucuronidase (GUS). Analysis of the Rca deletion mutants
      localized the region conferring normal expression downstream from -294 relative
      to the Rca transcription start site. A second set of transgenic plants containing
      the cauliflower mosaic virus (CaMV) 35S enhancer fused to the 3' end of the
      Rca/GUS constructs demonstrated the presence of a light-responsive element
      between -150 and -78 active in leaves. Regions 10 bp long within the light
      responsive region, which included putative G box and GT elements, were removed by
      recombinant polymerase chain reaction. Deletion of the G box element resulted in
      a loss of gene expression in the leaves of transgenic tobacco, while deletion of
      the GT motif caused a 10-100-fold increase in expression in roots. However, site
      directed mutagenesis of the GT motif resulted in expression patterns identical to
      the normal promoter. These experiments demonstrated that light-inducible and
      tissue-specific expression of the Rca promoter involves multiple cis elements
      proximal to the transcription start site, and that interactions between these
      elements are essential for regulating expression.

PMID- 8292779
TI  - Ubiquitous nuclear proteins bind to 5' upstream region of major Kunitz
      chymotrypsin inhibitor gene in winged bean.
AB  - Winged bean Kunitz chymotrypsin inhibitor (WCI) accumulates abundantly in seeds
      and tuberous roots of winged bean plant. In seeds, the WCI mRNA is observed
      transiently during seed maturation period. The WCI is encoded by a multigene
      family and the major WCI (WCI-3) is encoded by two nearly identical genes (WCI-3a
      and WCI-3b genes), in which nucleotide sequences in the 1.1 kb 5' flanking
      regions are about 99% homologous to each other and the transcribed regions are
      completely identical. Here we report the detection of two types of nuclear
      proteins which bind to the multiple sites in the 5' upstream region of the WCI-3a
      gene. One of the proteins, band 1-forming protein, also bound to cauliflower
      mosaic virus 35S (CaMV35S) promoter, but another protein, band 3-forming protein,
      did not. DNaseI footprinting analysis showed that these proteins bound to AT-rich
      upstream regions in the WCI-3a gene. Addition of poly(dA-dT)-poly(dA-dT) to the
      binding reaction inhibited the formation of the retarded bands, while poly(dI-dC)
      poly(dI-dC) did not. In various organs and throughout seed maturation period,
      proteins with invariable binding specificities were detected, and these binding
      proteins met some operational criteria for high-mobility-group (HMG) proteins.
      These results suggest that leguminous seed AT-binding proteins reported on
      several seed storage protein genes may be HMG-like proteins which are present
      ubiquitously in plant organs.

PMID- 8292780
TI  - Organization and structure of the 1-aminocyclopropane-1-carboxylate oxidase gene
      family from Petunia hybrida.
AB  - In this paper we present the structural analysis of the 1-aminocyclopropane-1
      carboxylate (ACC) oxidase gene family from Petunia hybrida. Southern blot
      analysis and restriction endonuclease mapping showed that two cloned regions of
      the petunia genome contained sequences highly homologous to a previously isolated
      ACC oxidase cDNA clone. Nucleotide sequencing of these two regions of the genome
      showed that each contained two tandemly arranged genes designated ACO1, ACO2,
      ACO3 and ACO4. Comparison of the nucleotide sequences of the cloned genomic
      regions with the cDNA clone pPHEFE indicated that ACO1 encoded the transcript in
      4 exons interrupted by 3 introns. The other three members of the petunia ACC
      oxidase gene family shared identical intron numbers and positions with ACO1 and
      their exons were greater than 80% homologous. Nucleotide substitutions and
      deletions in the ACO2 gene indicate that it likely represents a pseudogene.
      Overall homology between ACO1 and ACO2 indicates that this gene cluster arose by
      a more recent duplication event than the gene duplication giving rise to the ACO3
      and ACO4 cluster. The 5-flanking sequences share little overall homology between
      members of this gene family. However, sequences which likely make up the core
      promoter of these genes including the TATA box are highly homologous. RNA-based
      PCR amplification of ACC oxidase cDNAs from ethylene-treated corollas and wounded
      leaves revealed transcripts for ACO1, ACO3 and ACO4 indicating that a least three
      of these genes are transcriptionally active. The proteins encoded by ACO1, ACO3
      and ACO4 share more than 90% identity with one another and more than 70% identity
      with ACC oxidases from other species. The ACC oxidase proteins share significant
      sequence homology with other enzymes that require Fe(II) and ascorbate for
      catalytic activity.

PMID- 8292781
TI  - Cruciferin gene families are expressed coordinately but with tissue-specific
      differences during Brassica napus seed development.
AB  - The major storage protein in seeds of Brassica napus, the 12S globulin
      cruciferin, is composed of three different groups of subunits; cru1, cru2/3 and
      cru4. By using gene family-specific probes, we have investigated the
      accumulation, rate of synthesis and spatial distribution of transcripts
      corresponding to the different groups of cruciferin subunits in developing seeds.
      Cruciferin transcripts derived from different gene families accumulate
      coordinately to comparable amounts during seed development. The corresponding
      gene families are, however, transcribed at different rates. Investigation of the
      spatial distribution of transcripts corresponding to each group of cruciferin
      subunits in the developing seed by in situ hybridization, revealed that mRNAs of
      all three types accumulate in both axis and cotyledons. Transcripts derived from
      cru1 and cru4 gene families show a similar cell specificity and accumulate in a
      similar spatial manner during seed development. In contrast, mRNAs corresponding
      to the cru2/3 gene family are expressed with a partly different cell specificity
      and show a slightly different pattern of accumulation in the axis and cotyledons,
      with a delayed accumulation in epidermal cells. In the cotyledons, the initial
      accumulation of this type of cruciferin mRNAs is also distinguished from the two
      other types. The differences in cell specificity are seen in the root cap and in
      provascular cells, where mRNAs belonging to the cru2/3 family are absent.

PMID- 8292782
TI  - Identification and molecular cloning of two homologues of protein phosphatase X
      from Arabidopsis thaliana.
AB  - In a recent paper [Arino et al., Plant Mol Biol 21: 475-485 (1993)] we reported
      the amplification of a DNA fragment (AP-2) from the genome of Arabidopsis
      thaliana encoding an amino acid sequence corresponding to a Ser/Thr protein
      phosphatase distantly related to type 2A protein phosphatases. In this paper we
      report the use of the AP-2 fragment to isolate several cDNA clones from a leaf
      cDNA library. Two of these (EP124 and EP129) largely overlap and contain the AP-2
      sequence, whereas a third clone (EP128) is different although very related in
      sequence (86% of identity). Clones EP124/EP129 and EP128 were found to encode two
      highly related polypeptides (93% identity) of 305 residues, showing a very high
      identity (83%) to the catalytic subunit of protein phosphatase X (PPX) from
      rabbit. Therefore, they have been named PPX-1 (EP124/EP129) and PPX-2 (EP128).
      Southern blot analysis of genomic DNA indicates that only these two genes
      encoding phosphatases closely related to PPX are present in the genome of A.
      thaliana. Both PPX-1 and PPX-2 are expressed at very low levels in A. thaliana
      flowers, leaves, stems and roots. The expression levels of four previously
      identified type 2A phosphatases are higher than those of PPX genes. PP2A-1
      appears to be the major mRNA species detected in all the tissues analyzed.

PMID- 8292783
TI  - A novel blue light- and abscisic acid-inducible gene of Arabidopsis thaliana
      encoding an intrinsic membrane protein.
AB  - Continuous irradiation with blue light (400-500 nm) induces flower formation in
      plantlets of Arabidopsis thaliana (C24) while red light (600-700 nm) is
      ineffective. This observation started a search for genes that are activated by
      blue light and initiate the morphogenic programme leading to flower formation.
      Several genes were identified via their cDNAs. From these clone AthH2, with an
      open reading frame for a hydrophobic 30.5 kDa polypeptide, was selected for
      further characterization of the corresponding gene. From a genomic library a DNA
      fragment of about 6.4 kb was isolated, comprising the coding region as well as 5'
      upstream and 3'-downstream flanking segments. The coding region is composed of
      four exons, which specify a polypeptide of 286 amino acids. Several potential
      regulatory elements were found between position -670 and -1140 including GA and
      ABA sequence motifs. The latter could account for the observed induction of the
      AthH2 gene by ABA. Southern blot analysis of Arabidopsis genomic DNA suggests
      that the AthH2 gene is encoded by a single-copy gene. Hydropathy plots and
      secondary structure analysis of the putative polypeptide predict six membrane
      spanning domains implicating a function as transmembrane channel protein. It
      displays significant homology with the proteins TR7a of pea (82%) and RD 28 of A.
      thaliana (68%).

PMID- 8292784
TI  - Phenotype and hormonal status of transgenic tobacco plants overexpressing the
      rolA gene of Agrobacterium rhizogenes T-DNA.
AB  - The rolA gene of the TL-DNA of Agrobacterium rhizogenes Ri-plasmid plays a major
      role in establishing the hairy root syndrome in transgenic plants. Transgenic
      tobacco plants (Nicotiana tabacum L.) expressing constitutively the rolA gene
      under the transcriptional control of the 35S RNA promoter show pronounced
      phenotypical alterations. P35S-rolA transgenic tobacco plants are characterized
      by stunted growth, dark green wrinkled leaves with an altered length-to-width
      ratio, condensed influorescences, retarded onset of flowering, a reduced number
      of flowers and shortened styles. To investigate whether the pleiotropic
      alterations of growth and development are linked to an altered hormonal status we
      have compared the immunoreactive content of indole-3-acetic acid, cytokinins,
      abscisic acid, gibberellin and the ethylene precursor 1-aminocyclopropane-1
      carboxylic acid (ACC) of seedlings and different tissues of P35S-rolA transgenic
      plants, transgenic plants expressing the rolA gene under control of its own
      phloem-specific promoter and wild-type plants. Multiple tissue-specific
      alterations of phytohormone concentrations are the consequence of rolA gene
      activity. Changes of phytohormonal content can explain part of the rolA-induced
      phenotypic alterations. Most strikingly, in young and fully developed leaves of
      rolA and P35S-rolA transgenic clones a 40-60% reduction of immunoreactive
      gibberellin A1 was found, as compared to wild-type leaves. Treatment of wild-type
      tobacco plants with inhibitors of gibberellin biosynthesis phenotypic alterations
      similar to those of rolA transgenic plants. This suggests that the reduction of
      gibberellic acid content is indirectly but causally involved in rolA-induced
      alterations of stem elongation and planar leaf blade growth.

PMID- 8292785
TI  - Two related, low-temperature-induced genes from Brassica napus are homologous to
      the human tumour bbc1 (breast basic conserved) gene.
AB  - In order to identify genes involved in cold acclimation, we have constructed a
      cDNA library from Brassica napus (cv. Samourai) cold-acclimated etiolated
      seedlings. By differential screening, a cDNA clone named pBnC24 (Brassica napus
      Cold), corresponding to a new cold-inducible plant gene, was isolated. Northern
      blot hybridizations using total RNA from acclimated and unacclimated seedlings
      confirmed that BnC24 represents a cold-regulated gene. In contrast with a number
      of cold-inducible plant genes, BnC24 does not seem to be responsive to abscisic
      acid (ABA). In addition, further screening of the 'cold-acclimated' cDNA library
      using pBnC24 cDNA as a probe, allowed the isolation of a second type of
      homologous cDNA. Sequence analysis showed that the two BnC24 genes encode basic
      24 kDa proteins, which are highly hydrophilic and rich in alanine, lysine and
      arginine. The nucleotide and deduced amino acid sequences of these clones do not
      show any homology with other previously described cold-induced plants genes.
      However they have strong homology with a recently discovered human tumour gene,
      bbcl (breast basic conserved), which seems to be highly conserved in eukaryotes.

PMID- 8292786
TI  - Identification and characterization of a proline-rich mRNA that accumulates
      during pod development in oilseed rape (Brassica napus L.).
AB  - Pod development in oilseed rape (Brassica napus) culminates in a process known as
      dehiscence (shatter) which can result in the loss of seed before the crop is
      harvested. In order to investigate the biochemical and the genetic basis
      controlling this process, a cDNA library was constructed from the dehiscence zone
      of developing pods. This resulted in the isolation of a cDNA clone (SAC51). The
      mRNA encoded by SAC51 had a transcript size of ca. 700 nucleotides and was found,
      by northern analysis, to accumulate preferentially in the dehiscence zone of the
      pod and in no other part of the plant analysed. The predicted polypeptide is rich
      in the amino acids proline (14.2%) and leucine (14.2%). The sequence of the
      polypeptide has more than 40% amino acid sequence identity with polypeptides
      isolated from carrot embryos, maize roots, soybean seeds and young tomato fruit.
      The function of these proteins is unknown. Genomic Southern analysis suggests
      that SAC51 is encoded by a single gene or small gene family. The role of the
      peptide in the development of pods of oilseed rape is discussed.

PMID- 8292787
TI  - cDNA-derived identification of novel thionin precursors in Viscum album that
      contain highly divergent thionin domains but conserved signal and acidic
      polypeptide domains.
AB  - The existence of new thionin variants in Viscum album has been deduced from cDNA
      sequences. Unlike the viscotoxins and related thionins previously found in
      different members of the Viscaceae, these novel thionins contain eight rather
      than six cysteine residues. In this respect they resemble thionins described
      previously from various cereals and from Pyrularia pubera, which also contain
      eight cysteine residues at identical positions. All of the new thionins of V.
      album are encoded as higher-molecular-weight precursors consisting of a signal
      peptide, a thionin domain and an acidic polypeptide domain. While the deduced
      amino acid sequences of the thionin domains of different precursor molecules are
      highly divergent, the two other domains are conserved among all of the variants
      and are distinct from the corresponding domains of thionin precursors of other
      plant species.

PMID- 8292788
TI  - Molecular cloning and evolutionary analysis of the calcium-modulated contractile
      protein, centrin, in green algae and land plants.
AB  - Centrin (= caltractin) is a ubiquitous, cytoskeletal protein which is a member of
      the EF-hand superfamily of calcium-binding proteins. A centrin-coding cDNA was
      isolated and characterized from the prasinophyte green alga Scherffelia dubia.
      Centrin PCR amplification primers were used to isolate partial, homologous cDNA
      sequences from the green algae Tetraselmis striata and Spermatozopsis similis.
      Annealing analyses suggested that centrin is a single-copy-coding region in T.
      striata and S. similis and other green algae studied. Centrin-coding regions from
      S. dubia, S. similis and T. striata encode four colinear EF-hand domains which
      putatively bind calcium. Phylogenetic analyses, including homologous sequences
      from Chlamydomonas reinhardtii and the land plant Atriplex nummularia,
      demonstrate that the domains of centrins are congruent and arose from the two
      fold duplication of an ancestral EF hand with Domains 1+3 and Domains 2+4
      clustering. The domains of centrins are also congruent with those of calmodulins
      demonstrating that, like calmodulin, centrin is an ancient protein which arose
      within the ancestor of all eukaryotes via gene duplication. Phylogenetic
      relationships inferred from centrin-coding region comparisons mirror results of
      small subunit ribosomal RNA sequence analyses suggesting that centrin-coding
      regions are useful evolutionary markers within the green algae.

PMID- 8292789
TI  - Characterization of Synechocystis sp. PCC 6803 in iron-supplied and iron
      deficient media.
AB  - The photosynthetic apparatus is rich in iron-containing cofactors and iron
      deficiency causes severe impairment of photosynthesis in plants, algae, and
      cyanobacteria. Synechocystis sp. PCC 6803 serves as a model system to investigate
      the complex assembly and integration of the multi-subunit protein complexes of
      oxygenic photosynthetic electron transport; particularly when coupled to
      developmental cues due to nutrient limitation or requirements. We study Fe(3+)
      deficient and Fe(3+)-supplemented cultures of Synechocystis sp. PCC 6803. The
      autotrophic growth rate of Fe(3+)-deficient cultures is slower than Fe(3+)
      supplemented cultures. Whole cell spectral analysis reveals differences in both
      the quantity and the peak absorbance of chlorophyll. Fe3+ deficiency decreases
      rates of photosynthetic electron transport and the mRNA and corresponding protein
      levels as observed using specific probes. mRNA levels of psaB increased 20-fold
      during recovery from Fe3+ deficiency, as compared to the control. psaD transcript
      levels increased to 160% during recovery as compared to the control. PsaA/B
      heterodimer formation and turnover is dependent on Fe3+ and the complete assembly
      on the reducing side of photosystem I (PS I) is PsaD-dependent. Recovery from
      Fe3+ deficiency suggests that regulation occurs at both the mRNA and protein
      level.

PMID- 8292790
TI  - Isolation and characterization of an Arabidopsis thaliana gene for the 54 kDa
      subunit of the signal recognition particle.
AB  - The first step in the routing of newly synthesized proteins into the secretory
      pathway is the binding of the nascent signal sequence to the signal recognition
      particle. The mammalian signal recognition particle is a complex consisting of 6
      proteins and a single 7S RNA molecule. Signal recognition particle-like complexes
      have been described from wheat and maize but none of the protein components have
      yet been described from any plant species. Here we report the cloning and
      characterization of an Arabidopsis thaliana gene encoding the 54 kDa protein
      subunit of the signal recognition particle. This is the first report of a SRP-54
      sequence for any plant species and the first genomic sequence for any
      multicellular organism.

PMID- 8292791
TI  - Isolation and characterization of a polygalacturonase gene highly expressed in
      Brassica napus pollen.
AB  - A cDNA clone, Sta 44-4, corresponding to a mRNA highly expressed in Brassica
      napus cv. Westar stamens, was isolated by differential screening and
      characterized. Northern blot and in situ analyses demonstrated that Sta 44-4 is
      synthesized in pollen beginning at the late uninucleate stage and reaches a
      maximum in trinucleate microspores. Sta 44-4 displayed significant sequence
      similarity to known pollen polygalacturonase genes. The B. napus pollen
      polygalacturonase gene was shown to be part of a small gene family and to display
      some polymorphism among different cultivars.

PMID- 8292792
TI  - Molecular characterization of multiple cDNA clones for ADP-glucose
      pyrophosphorylase from Arabidopsis thaliana.
AB  - PCR amplification of cDNA prepared from poly(A)+ RNA from aerial parts of
      Arabidopsis thaliana, using degenerate nucleotide primers based on conserved
      regions between the large and small subunits of ADP-glucose pyrophosphorylase
      (AGP), yielded four different cDNAs of ca. 550 nucleotides each. Based on derived
      amino acid sequences, the identities between the clones varied from 49 to 69%.
      Sequence comparison to previously published cDNAs for AGP from various species
      and tissues has revealed that three of the amplified cDNAs (ApL1, ApL2 and ApL3)
      correspond to the large subunit of AGP, and one cDNA (ApS) encodes the small
      subunit of AGP. Both ApL1 and ApS were subsequently found to be present in a cDNA
      library made from Arabidopsis leaves. All four PCR products are encoded by single
      genes, as found by genomic Southern analysis.

PMID- 8292793
TI  - The stromal processing peptidase activities from Chlamydomonas reinhardtii and
      Pisum sativum: unexpected similarities in reaction specificity.
AB  - We have partially purified the stromal processing peptidase from Chlamydomonas
      reinhardtii and compared the properties of this activity with those of the pea
      counterpart. Whereas previous studies have suggested that the two enzymes may
      have significantly different reaction specificities, we find that they are in
      fact very similar. Both enzymes process precursors of two higher-plant thylakoid
      lumen proteins, and one C. reinhardtii lumenal protein, to similar intermediate
      size forms. However, whereas the algal enzyme processes the precursor of C.
      reinhardtii Rubisco small subunit to the correct mature size, this precursor is
      cleaved only to an intermediate size by the pea enzyme. The small subunit
      precursor from pea appears to be cleaved by both enzymes in a similar manner. In
      terms of sensitivity to inhibitors, the two activities are notably different; the
      pea enzyme has previously been shown to be inhibited by several types of heavy
      metal chelator, but we have found that none of these compounds affect the algal
      activity.

PMID- 8292794
TI  - Persistent vegetative state--clinical and electrophysiologic observations of 5
      cases.
AB  - Five patients who met the criteria of the persistent vegetative state (PVS), were
      studied for ten years. Among them, two had fallen into a deep coma after
      cardiopulmonary resuscitation, and the other three cases were due to
      cerebrovascular disorders. Four patients died within 10 years. Clinically, all
      five cases showed characteristic features of wakefulness without cognitive
      function and movement of the extremities. The brain stem reflexes, such as light
      reflexes of the pupils and corneal reflexes, were present. The
      electroencephalograms showed ample low amplitude and nonspecific slow waves. None
      revealed an isoelectric pattern. Brain stem auditory evoked potential (BAEP)
      studies were normal or slightly abnormal. Median nerve somatosensory evoked
      potential (SSEP) studies showed absence of a cortical response. These features
      suggest that the damage in PVS patients is mainly located in the cerebral cortex.
      Although electrophysiologic examinations are useful diagnostic procedures for
      PVS, clinical observation remains the basis of the diagnosis.

PMID- 8292795
TI  - Prevalence and epidemiologic correlates of sexually transmitted Chlamydia
      trachomatis infection in a selected population.
AB  - The incidence of Chlamydia trachomatis genitourinary infection was found by
      enzyme immunoassay antigen detection to be 10.0% in patients attending a sexually
      transmitted disease (STD) clinic, 3.0% in clients visiting an obstetrics
      gynecology clinic, 20.8% in female prostitutes, and 1.3% in sexually active men.
      Predisposing factors for chlamydial infection were young age, multiple sexual
      partners, history of STDs, and coinfection with other STDs. Abnormal vaginal
      discharge and cervices in women, but not urethral manifestations in men, were
      significantly associated with chlamydial infection. Urethral gram stain had a
      certain value in identifying men infected with C. trachomatis.

PMID- 8292796
TI  - Molecular biology of human papillomavirus.
AB  - The papillomavirus is at present considered to be an independent group of
      viruses, possibly an independent family. Human papillomavirus (HPV) can cause
      warts of the skin and mucosa, and is now widely recognized as an important
      etiologic factor of both benign and malignant tumors in the lower genital tract.
      In this paper the biological properties of HPV, including its genomic
      organization and the open reading frames, are described; the relationship between
      HPV and uterine cervical carcinoma, especially in regard to the role of the viral
      oncogenes E6 and E7, is discussed in detail.

PMID- 8292797
TI  - Follow-up of asymptomatic myocardial ischemia in patients with diabetes mellitus.
AB  - Early detection of asymptomatic myocardial ischemia in patients with diabetes
      mellitus (DM) is very important for the prevention of painless myocardial
      infarction. The purpose of this study is to explore the clinical significance of
      asymptomatic transient ST changes in ECG in patients with DM and to further
      clarify the relation between asymptomatic myocardial ischemia and myocardial
      infarction in DM.

PMID- 8292798
TI  - Clinicopathologic analysis of 60 cases of basal cell carcinoma.
AB  - An analysis of 60 cases of basal cell carcinoma is reported. Among the 60
      patients were 29 men and 31 women (1:1.1). Their ages ranged from 22 to 88, with
      an average of 58.8 years. The courses were from 2 months to more than 20 years,
      with 50% being less than 5 years. The head and face were the main sites involved.
      The etiology, clinical appearance, pathologic classification, and clinical
      therapy of the basaloma are discussed briefly. To minimize the patient's
      psychological burden, and according to the low rate of metastasis, we suggest
      that the tumor be designated basaloma or basal cell epithelioma rather than basal
      cell carcinoma.

PMID- 8292799
TI  - Early diagnosis of typhoid fever using monoclonal antibody.
AB  - In our study, a reverse passive hemagglutination assay (RPHA) method was
      established using monoclonal antibody-IgM to detect the Salmonella typhi O9
      antigen. This method has the advantages of sensitivity, specificity, rapidity,
      and simplicity, and helps make an early diagnosis of typhoid fever using only
      small amounts of blood.

PMID- 8292800
TI  - Changes of calmodulin contents in single vascular smooth muscle cells from the
      tail arteries of spontaneously hypertensive rats.
AB  - By combining immunohistochemistry and fluorocytometry techniques, total
      calmodulin (total CaM), Ca(2+)-bound calmodulin (Ca.CaM) and total protein
      contents in single vascular smooth muscle cells (VSMC) enzymatically dispersed
      from the tail arteries of young (5-7 weeks old, prehypertensive) and adult (20-24
      weeks old, established hypertensive) stroke-prone spontaneously hypertensive rats
      (SHRsp) were studied and compared with those of age-matched Wistar-Kyoto rats
      (WKY). No significant difference was found in total CaM, Ca.CaM and protein
      contents between young SHRsp and WKY. Total CaM and protein contents in adult
      SHRsp were increased by similar degrees (30.7% and 27.5%, respectively) as in age
      matched WKY, suggesting that increased total CaM content may be a consequence of
      increased synthesis of cellular protein during hypertension. However, Ca.CaM
      contents in adult SHRsp were significantly increased over those in age-matched
      WKY by a much higher degree (86.2%), reflecting an abnormal Ca2+ homeostasis in
      single VSMCs during hypertension.

PMID- 8292801
TI  - The effect of laminin on molecular motion in the cell membrane and on cell
      motility.
AB  - We have studied the variation of lateral diffusion of proteins in the cell
      membrane, of membrane lipid fluidity and of the electrophoretic motility (EPM) of
      macrophages after treatment with extrinsic laminin. The results showed that the
      lateral diffusion coefficient D value of membrane proteins, the fluidity of
      membrane lipids and the EPM of macrophages were decreased after laminin had bound
      to its membrane receptor on the macrophages. These results are important for
      developing an understanding of the early reaction of plasma membranes and cells
      in the presence of laminin.

PMID- 8292802
TI  - Hemodynamic and nonhemodynamic mechanisms of experimental pulmonary edema in rats
      and the effect of anisodamine and tetramethylpyrazine. Part 1: Survival rate,
      pulmonary index, pathological change and pulmonary vascular permeability.
AB  - Pulmonary edema (PE) which is similar to the neurogenic type was induced by
      adrenaline (AD) administration (0.1 mg/kg) in rats. Acute progressive respiratory
      distress, cyanosis and dyspnea occurred. All the experimental animals in the PE
      group died within 20 min after AD injection, with a pulmonary index (PI) of 1.70
      +/- 0.47 (mean +/- S) which was much higher than that in the normal group. The
      mortality rate was 100%. It was found that in rats with PE, a protein-rich fluid
      filled the alveolar and interstitial spaces, and ecchymosis occurred. The
      capillary permeability as estimated by Evans blue injection showed that Evans
      blue from extraction fluid and bronchoalveolar lavage (BAL) in the PE rats was at
      a much higher level than that in the normal control (NC) rats. In anisodamine
      (ADM, 654-2) and tetramethylpyrazine (TMP) treated rats, almost all the damage
      was diminished or absent, and the mortality rates were decreased from 100% to
      4.4% and 20%, respectively. 654-2 and TMP could significantly inhibit the
      increase of pulmonary permeability.

PMID- 8292803
TI  - Role of respiration related units in the nucleus retrofacialis region in rats.
AB  - Experiments were carried out on 10 urethane anesthetized, spontaneously breathing
      rats. The distribution of respiration related units (RRUs) in the nucleus
      retrofacialis (NRF) region was explored systematically with an extracellular
      recording technique and their discharging patterns were analyzed through a
      microcomputer. A total of 212 spontaneously discharging units were recorded in
      the NRF region. Among them 120 were RRUs and the remainder were non-respiration
      related units (NRRUs). Among the RRUs, 28 were determined to be inspiration
      related units (InRUs); 81 were expiration related units (ExRUs) and 11 were phase
      spanning respiration related units (PSUs) according to their temporal relation to
      phrenic activity. These RRUs were further classified into augmenting,
      decrementing and constant types based on their discharge patterns. The results
      indicated that RRUs in the NRF region were relatively abundant as compared to
      NRRUs, and they were more concentrated in the medial part of the NRF region
      (mNRF). Among them, ExRUs were predominant.

PMID- 8292804
TI  - Soft X-ray microimages of immunogold-labelled tumor cell surface antigens.
AB  - After successfully introducing the colloidal immunogold labelling technique to
      soft X-ray contact microscopy (SXCM), SXCM replica microimages of immunogold
      labelled tumor cell HLA-A2 surface antigens have been acquired for the first
      time. A biological sample preparation method using immunocytochemical staining
      techniques suitable for SXCM has also been established.

PMID- 8292805
TI  - Immunological studies on the pathogenesis of pterygium.
AB  - Immunohistochemical, electron microscopic and routine pathological studies were
      conducted to observe the changes in T-cell subsets, B-cells, plasma cells, and
      mast cells, and the distributions of immunoglobulins (IgE, IgG, IgA, IgM) and C3
      in patients with pterygium. The results were as follows. Massive amounts of
      infiltrating lymphocytes, predominantly T-cells (CD3+), were found in the
      substantia propria of the pterygial specimens. The helper-suppressor ratio had
      risen from 1:2.7 in the normal conjunctiva to 1:1.5. Positive cytoplasmic
      immunoglobulin staining indicated a plasmocytic infiltration in the lesions as
      well. Abnormal distributions of immunoglobulins were found, and deposition of
      immunoglobulins in a granular pattern around the basement membrane of the
      epithelial layer was seen. Mast cell reactions were found, and a linear
      correlation between the numbers of lymphocytes and mast cells was shown. Basement
      membrane destruction in the cap area of the pterygium was also confirmed. These
      results indicate that an immunologic mechanism, possibly of Types 1, 3 and 4
      hypersensitivity, may contribute to the pathogenesis of pterygium.

PMID- 8292806
TI  - Comparison of parathyroid donor grafts.
AB  - We compared the degrees of cell maturity, antigenicity and secretory function of
      parathyroid tissues (PTG) from cadavers (C-PTG), 20-28 week fetuses (F-PTG) and
      PTG adenomas (A-PTG). In A-PTG, scattered or clustered immature cells were
      observed, but there were none in F-PTG and C-PTG tissues. A-PTG and C-PTG
      exhibited better secretory function than did F-PTG. No clear differences were
      found in HLA class I (ABC) antigen quantity among the three donor PTG tissues,
      but the amounts of HLA class II (DR) antigen in A-PTG and F-PTG were
      significantly lower than that in C-PTG. The results demonstrate that C-PTG, with
      its functional advantages, and F-PTG, with its relatively low antigenicity, can
      be used in clinical transplantation, while A-PTG tissues are not suitable for
      clinical transplantation on account of their immaturity and the possibility of
      carcinomatous change.

PMID- 8292807
TI  - Intelligence function in children with acute lymphoblastic leukemia after
      treatment.
AB  - In order to evaluate the effects of chemotherapy and central nervous system
      prophylaxis on the intelligence function of children with acute lymphoblastic
      leukemia (ALL), 147 patients were divided into 2 groups according to their
      different treatment regimens. Group A included 75 patients with ALL who were
      diagnosed and treated from 1981 to 1986. Group B included 72 ALL patients
      diagnosed and treated from 1988 to 1990. A control group included 73 healthy
      children who shared the same education and environmental background with the
      patients. Chinese revisions of Wechsler measures of intelligence quotient were
      used to estimate verbal IQ, performance IQ and total IQ in the 3 groups. American
      produced Systate software was used to analyze the data. Results showed that IQ
      distribution, verbal IQ, performance IQ and total IQ of group A were obviously
      lower than those in the control group. Verbal IQ and total IQ of group B were
      also reduced. Significant differences of verbal IQ and performance IQ as well as
      total IQ were also found between groups A and B. Multiple regression analysis
      showed negative correlations between IQ and cranial irradiation dosage, times of
      intrathecal MTX and time after irradiation.

PMID- 8292808
TI  - Misdiagnosis of lung cancer in patients under age 40--a clinical analysis of 47
      cases.
AB  - Diagnosis of lung cancer in 47 patients aged younger than 40 years was delayed as
      a result of misdiagnosis, accounting for 70.1% of all cases of lung cancer in
      those aged less than 40 years treated in PUMC Hospital in the same period.
      Pulmonary tuberculosis and tuberculous pleurisy were diagnosed in 26 cases
      (55.3%). Pulmonary inflammation was suspected in 24 cases (51.1%). The delay in
      diagnosis was one to three months in 28 cases and longer than 3 months in 19
      cases. Twenty-eight (59.6%) of the 47 patients underwent surgery, including
      exploratory thoracotomy (21.4%) and pneumonectomy (40.9%). The five-year survival
      rates in the resectable group and in the non-surgical group were 31.6% and 5.3%,
      respectively. We recommend that accessory examinations should be performed
      wherever possible in younger patients with suggestive pulmonary nodules in order
      to collect sufficient evidence to confirm or rule out the diagnosis of lung
      cancer and thereby reduce the rate of misdiagnosis in such younger people.

PMID- 8292809
TI  - Prevention and treatment of organ toxicity during high-dose chemotherapy: an
      overview.
AB  - By using increased doses or dose intensities of cytostatic agents, improvements
      in clinical outcome may be achieved in some cancer cases. However, high-dose
      chemotherapy may produce dose-limiting adverse reactions such as
      myelosuppression, neurotoxicity, cardiotoxicity, gastrointestinal toxicity,
      nausea and vomiting. The use of bone marrow transplantation, autologous infusion
      of circulating hematopoietic progenitors and hematopoietic growth factors have
      been shown to significantly reduce the severity and duration of the pancytopenia
      associated with cytostatic chemotherapy and chemoradiotherapy. In addition,
      recent developments in the control of nausea and vomiting with selective 5-HT3
      antagonists have improved the tolerability of chemotherapy. The antiemetic
      efficacy of these agents has been shown to be equivalent to combination therapy
      with metoclopramide plus dexamethasone in the prevention of cisplatin-induced
      emesis. Progress in the prevention and treatment of organ toxicity is now
      required, if treatment with higher doses and dose intensities of cytostatic drug
      treatments are to be used for the future treatment of human malignancies.

PMID- 8292810
TI  - Characterization by flow cytometry and fluorescein-methotrexate labeling of
      hydrophilic and lipophilic antifolate resistance in cultured mammalian cells.
AB  - The aim of this review is to summarize currently available information on the
      rapid screening and initial characterization of the different mechanisms of
      resistance to hydrophilic [e.g. methotrexate (MTX)] and lipophilic antifolates
      [e.g. trimetrexate (TMTX)] in cultured mammalian cells using fluorescein
      methotrexate (F-MTX) and flow cytometry. Toward this end an integrative F-MTX
      labeling and flow cytometry-based protocol is proposed here to facilitate the
      rapid identification of modes of antifolate resistance in a heterogenous drug
      resistant cell population or in clonal derivatives. Following antifolate
      selection, drug-resistant cells are first labeled with F-MTX in order to saturate
      intracellular dihydrofolate reductase (DHFR). F-MTX-labeled cells are then
      subjected to flow cytometric analysis and mean fluorescence/cell is determined.
      Thus, increased F-MTX staining is an indication of overproduction of the target
      enzyme for antifolates, DHFR, as a result of DHFR gene amplification. In
      contrast, significantly reduced cellular F-MTX labeling could be an indication of
      the existence of a structurally altered DHFR displaying a decreased affinity for
      antifolates. Alternatively, antifolate-resistant cells frequently display wild
      type F-MTX labeling; these cells are subjected to competition with hydrophilic
      and lipophilic antifolates in order to examine whether the process of antifolate
      accumulation is deficient. Cells that lose F-MTX labeling upon competition with
      lipophilic antifolates yet still retain it with hydrophilic antifolates, are
      likely to possess transport alteration(s) that impair or abolish the accumulation
      of hydrophilic but not of lipophilic antifolates. In contrast, cells that lose
      their F-MTX labeling after competition with hydrophilic antifolates but retain it
      with lipophilic antifolates, possess a deficient accumulation of lipophilic
      antifolates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292811
TI  - Measurement of aspartate carbamoyltransferase activity by high performance liquid
      chromatography.
AB  - We developed an assay which permits measurement of aspartate carbamoyltransferase
      (ACTase) activity. Cytosol from human peripheral blood mononuclear cells was used
      as the enzyme source. Using [14C]carbamoyl phosphate as the radiolabeled
      substrate, the formation of [14C]carbamoyl aspartate was quantitated by high
      performance liquid chromatography (HPLC) using an anion-exchange column with UV
      detection at 200-280 nm and an on-line liquid scintillation detector. A gradient
      method from an initially low concentration of ammonium phosphate, 1 mM (pH 3.0),
      to a higher concentration, 38 mM (pH 4.5), was used. The apparent Km values of
      carbamoyl phosphate and aspartate were 58 microM and 1.9 mM, respectively. ACTase
      inhibition by N-(phosphonacetyl)-l-aspartate (PALA) was consistent with a
      competitive model with respect to carbamoyl phosphate. The assay conditions were
      optimized to permit measurement of ACTase activity prior to and following therapy
      with PALA; ACTase was inhibited in a dose-dependent manner. This HPLC method
      permits direct quantitation of both the product of the reaction and the initial
      integrity of the substrate, [14C]carbamoyl phosphate, which is unstable in
      aqueous solutions.

PMID- 8292812
TI  - A phase II study of 5-fluorouracil, leucovorin and interferon-alpha in advanced
      pancreatic cancer.
AB  - Increased activity against colorectal cancer by 5-fluorouracil (5-Fu) modulation
      with leucovorin (LV) and/or interferon (IFN) has been reported. In this study 22
      patients with measurable advanced pancreatic cancer received 5-Fu 375 mg/m2 and
      LV 20 mg/m2 by i.v. bolus daily x 5 every 28 days plus IFN-alpha 3 million
      units/m2 s.c. There were three out of 21 (14%) responses lasting from 4 to 8
      months. Sixteen patients (73%) had one or more episodes of grade 3 or greater
      toxicity (stomatitis, diarrhea or fatigue). While this combination has some
      activity against pancreatic cancer, its toxicity limits its potential as a
      palliative treatment.

PMID- 8292813
TI  - Substitution of l-leucovorin for d,l-leucovorin in the rescue from high-dose
      methotrexate treatment in patients with osteosarcoma.
AB  - Studies in which high-dose methotrexate (HDMTX) is used for the treatment of
      osteosarcoma have utilized commercial formulations of d,l-leucovorin (leucovorin
      calcium) for rescue from potential methotrexate (MTX) toxicity. These
      formulations are racemic mixtures containing equal amounts of d and l isomers of
      leucovorin. All of the available data indicate that the l isomer is the
      pharmacologically active diastereomer. A clinical study was conducted to
      determine if l-leucovorin was as safe and efficacious as d,l-leucovorin in the
      rescue of patients with osteosarcoma who were treated with HDMTX (12.5 g/m2 over
      6 h). Because d,l-leucovorin consists of equal proportions of d and l isomers, l
      leucovorin was administered at half the usual dose of d,l-leucovorin. In patients
      with delayed methotrexate excretion, l-leucovorin doses were escalated from 7.5
      to 50 mg every 3 h until the MTX level was 0.3 mumol/l or less. Due to the low
      incidence of osteosarcoma, a control group of patients previously treated with
      d,l-leucovorin was utilized for comparison. Efficacy of l-leucovorin was
      determined by its ability to prevent HDMTX-associated toxicity. Demographic and
      clinical toxicity data from three patients who received 22 courses of MTX rescued
      with l-leucovorin were compared with data from six patients who had received 42
      MTX courses rescued with d,l-leucovorin. Some liver function abnormalities and
      leukocyte elevations were found in both groups and were attributed to MTX
      administration. No clinical toxicity attributable to l-leucovorin was observed. l
      Leucovorin in half the d,l-leucovorin dose was (equally) effective as a rescue
      treatment.

PMID- 8292814
TI  - Enhancement of phytohemagglutinin-induced lymphoproliferative response by
      indomethacin, Thymex L or their combination in lung cancer patients.
AB  - Several studies showed that thymic factors and prostaglandin synthesis inhibitors
      enhance in vitro lymphoproliferative response (LPR) to mitogens in cancer
      patients. In this study we investigated whether indomethacin and thymic extract
      (Thymex L), applied in combination, may in a synergistic pattern influence
      phytohemagglutinin-induced LPR in lung cancer patients. The results demonstrate
      that the use of the investigated agents enhances LPR to a similar level in
      hyporeactive patients before, as well as after, therapy. However, this drug
      combination exerts an additive effect on LPR, but only in patients who underwent
      cytoreductive radiation therapy, indicating the potential usefulness of this drug
      combination as an adjuvant treatment of these patients.

PMID- 8292815
TI  - Chemosensitivity testing of primary cultures of Merkel cell cancer.
AB  - Twenty-seven tumor specimens from patients with Merkel cell carcinoma (MCC) were
      tested for chemosensitivity against a battery of nine cytotoxic drugs in a short
      term antimetabolic assay measuring inhibition of thymidine incorporation. Dose
      response curves were constructed by plotting drug concentration in micrograms/ml
      versus % control [3H]thymidine incorporation. Specimens were considered
      'sensitive' to a drug if, at the approximate peak plasma concentration (PPC), the
      inhibition of [3H]thymidine was greater than 50% when compared with untreated
      control primary cultures. The assay revealed a 'sensitive' tumor in 19 of 20
      specimens and 16 of 17 patients had a tumor that was 'sensitive' to at least one
      drug tested in the assay system. The highest sensitivity in order of frequency
      was found with doxorubicin, epirubicin, cyclophosphamide, etoposide and
      cisplatin. At least 40% of the tumors were 'sensitive' to these five drugs.
      Cyclophosphamide was chosen as the most active drug (at PPC) in 10 of 19 assays
      (53%), etoposide in seven of 17 (41%), doxorubicin in four of 19 (21%),
      chlorambucil in one of 12 (8%) and cisplatin in one of 18 (5%) of assays. Though
      our results are preliminary, we have identified for the first time a range of
      cytotoxic drugs which appear effective against MCC in vitro. Our main task now is
      to determine whether our in vitro predictive assay will correlate with clinical
      benefit to the patient.

PMID- 8292816
TI  - Combination effect of navelbine (vinorelbine ditartrate) with cisplatin against
      murine P388 leukemia and human lung carcinoma xenografts in mice.
AB  - The in vivo combination effect of navelbine (NVB, KW-2307) plus cisplatin was
      compared with that of vindesine (VDS) plus cisplatin in terms of antitumor
      activity and side effects. The antitumor activity of NVB or cisplatin against
      i.p. inoculated P388 leukemia was augmented by their combination on various
      schedules when the interval of administrations was within 24 h. Against i.v.
      inoculated P388 leukemia, the most significant combination effect was observed
      when cisplatin was administered 4 h after NVB injection (ILS(%) > 451) and three
      long-term survivors were observed. On this schedule, the combination of LD10 of
      each drug was achieved, indicating the lack of addition of toxicity. This was
      further proved by examination of body weight change, white blood cell count and
      platelet count. Interestingly, significant elevation of blood urea nitrogen
      concentration by cisplatin was prevented by the combination with NVB. The
      combination of maximum tolerated dose of NVB and cisplatin was also tolerable in
      nude mice, and their combination effect was observed against human lung large
      cell carcinoma Lu-65 and adenocarcinoma PC-12. The number of toxic death mice was
      more in VDS plus cisplatin-treated groups than in NVB plus cisplatin-treated
      groups, indicating that the combination chemotherapy of NVB plus cisplatin is a
      better regimen than that of VDS plus cisplatin in experimental tumor systems.

PMID- 8292817
TI  - Low dose megestrol acetate can abrogate cachexia in advanced tumor patients
      receiving systemic interferon-alpha and/or interleukin-2 based antineoplastic
      therapy.
AB  - The progression of advanced malignancies is often associated with anorexia and
      cachexia, especially when patients receive concomitant systemic antitumor
      treatment. Megestrol acetate has been reported to increase appetite and body
      weight, and a linear dose-response relation for doses from 160 up to 1600 mg/day
      has been proposed. In our study, we were able to show that megestrol acetate at
      doses as low as 60 mg/day was sufficient to abrogate anorexia and weight loss. In
      contrast to previous studies, this effect was achieved while patients continued
      systemic antineoplastic therapy.

PMID- 8292818
TI  - Anticancer activities of 2,3-dihydro-1,4-benzothiazines, and of their 4-(N-alkyl
      amides) and 4-(N-alkyl N-nitrosoamides).

PMID- 8292819
TI  - Purification and characterization of a flavin-binding storage protein from the
      hemolymph of Galleria mellonella.
AB  - The 85K storage protein that accumulates in the hemolymph of Galleria mellonella
      during the final larval instar was isolated and purified from newly molted pupae.
      The separation of fresh hemolymph proteins from larvae or pupae by different
      chromatographic and electrophoretic procedures indicated the native protein had a
      M(r) of 170,000 and consisted of two identical 85K subunits. Crosslinking
      experiments using fresh hemolymph followed by Western blotting also indicated a
      dimeric structure for the native protein. Analyses of the dimer purified from
      pupal hemolymph indicated that 85K was a glycoprotein, containing approximately
      6.5% neutral sugar and about 1.9% amino sugar. Like other insect flavin-binding
      proteins, 85K has a relatively high histidine content but an uncharacteristically
      high arginine content. The purified 85K dimer did not bind riboflavin, suggesting
      that the integrity of the molecule had been altered during purification. However,
      85K purified in low yield by Affi-Gel Blue chromatography, did bind riboflavin,
      indicating that under certain, undefined conditions the functional integrity of
      the protein could be retained during purification.

PMID- 8292821
TI  - Cell-cell communication correlates with pattern formation in molting Manduca
      midgut epithelium.
AB  - The midgut epithelium of larval Manduca sexta is constructed of single goblet
      cells surrounded by a one-cell-thick reticulum of columnar cells. This pattern is
      expanded at each molt by the addition of new cells. Between molts, these
      epithelial cells are not dye coupled, even though gap junctions are present.
      Proliferating stem cells are dye coupled in small groups early in the molt. Then,
      at mid-molt, the whole epithelium temporarily becomes dye coupled. This is when
      the new (expanded) pattern is being established. Later, at the end of the molt,
      the epithelium returns to the non-coupled state. These results suggest that cell
      communication via gap junctions may play a role in cell patterning.

PMID- 8292820
TI  - Steady-state gradient in calcium ion activity across the intercellular bridges
      connecting oocytes and nurse cells in Hyalophora cecropia.
AB  - Intracellular activities of K+, H+, Mg2+, Ca2+, and Cl-, measured with ion
      selective microelectrodes in the oocyte and the nurse cells in ovarian follicles
      of Hyalophora cecropia, indicated that a Ca2+ current is a key component of the
      electrical potential that is maintained across the intercellular bridges
      connecting these two cells. In vitellogenic follicles, Ca2+ activity averaged 650
      nM in the oocyte and 190 nM in the nurse cells, whereas activities of the other
      ions studied differed between these cells by no more than 6%. Incubation in 200
      microM ammonium vanadate caused a reversal of electrical potential from 8.3 mV,
      nurse cell negative, to 3.0 mV, oocyte negative, and at the same time the Ca2+
      gradient was reversed: activities rose to an average 3.0 microM in the nurse
      cells and 1.6 microM in the oocyte, whereas transbridge ratios of the other
      cations remained at 0-3%. In immature follicles that had not yet initiated their
      transbridge potentials, Ca2+ activities averaged approximately 2 microM in both
      oocyte and nurse cells. The results suggest that vitellogenic follicles possess a
      vanadate-sensitive Ca2+ extrusion mechanism that is more powerful in the nurse
      cells than in the oocyte.

PMID- 8292822
TI  - Developmental analysis of the external granular layer in the meander tail mutant
      mouse: do cerebellar microneurons have independent progenitors?
AB  - The cerebellum of the meander tail mutant mouse (mea/mea) is characterized by an
      apparently normal cytoarchitecture posteriorly with an abrupt transition to an
      abnormal anterior region. Anteriorly, there is abnormal foliation, a drastic
      reduction in the granule cells (GC) population, disorganization of the Purkinje
      cells (PC), and a virtual absence of Bergmann glial processes. In this paper we
      analyze the prenatal and postnatal development of the cerebellum in the mea/mea
      and attempt to determine the phenotypic onset of the mutation in the anterior
      region. Hematoxylin and eosin stained sections reveal a morphological difference
      in the cerebellum of the mea/mea as early as embryonic day 16 characterized by a
      reduction in the external granule cell layer (EGL). The reduction in the EGL
      becomes increasingly apparent as development proceeds. This deficit in the EGL
      most probably results in the absence of GC, but it is unclear at this point
      whether reduced migration, proliferation, and/or increased cell death is the
      major factor. Interestingly, immunohistochemical staining with a monoclonal
      antibody against parvalbumin reveals that the basket and stellate cells, which
      are also thought to arise from the EGL, are present in the anterior region of the
      mea/mea cerebellum. These results suggest that the lack of GC in the meander tail
      is due to an early expressed abnormality of the EGL. However, the presence of the
      basket and/or stellate cells raises some interesting questions concerning the
      lineage of the cerebellar microneurons.

PMID- 8292823
TI  - Cellular origin of the dermal-epidermal basement membrane.
AB  - The basement membrane underlying epithelium of skin is generally believed to be
      of epithelial origin, but a mesenchymal contribution to the basement membrane has
      not been directly examined. The purpose of this study was to directly evaluate
      both epithelial and mesenchymal contributions to the basement membrane. Fetal
      bovine keratinocytes cultured on the surface of collagen gels in the absence of
      fibroblasts did not produce an ultrastructurally recognizable basement membrane;
      however, when these cells were cultured in the presence of dermal fibroblasts a
      basement membrane at the keratinocyte-fibroblast interface was produced after 1
      week which was very similar in biochemical composition and ultrastructural
      appearance to dermal-epidermal basement membrane in human skin. When dual species
      cultures of bovine keratinocytes and human fibroblasts were analyzed by indirect
      immunofluorescent microscopy (IF)1 with human specific antibodies against
      basement membrane components, dermal fibroblasts were shown to synthesize and
      deposit type IV collagen, type VII collagen, and laminin in a linear manner into
      the basement membrane zone. Fetal bovine keratinocytes cultured in the presence
      or absence of fibroblasts synthesized and deposited type IV collagen, type VII
      collagen, laminin, K-laminin, kalinin, and basement membrane associated heparan
      sulfate proteoglycan (HSPG) into the underlying basement membrane zone. In organ
      culture, a subpopulation of fibroblasts initially migrating from human foreskin
      explants was found to stain strongly for types VII and IV collagen and laminin by
      IF whereas after subculture all cells showed a uniform low staining. Based on
      these observations we propose that differentiated fibroblasts exist adjacent to
      epithelial tissues in vivo which produce basement membrane components and assist
      in basement membrane assembly.

PMID- 8292824
TI  - Induction of neuronal differentiation by planar signals in Xenopus embryos.
AB  - The induction of the central nervous system in amphibian embryos is mediated both
      by early planar signals produced by mesoderm at the dorsal lip and later vertical
      signals emanating from the dorsal mesoderm after involution. We have examined the
      role and spatial extent of planar signals in the induction of neuronal
      differentiation. Planar explants that included only the deep layer of the dorsal
      marginal zone, comprising both the dorsal mesoderm and the contiguous dorsal
      ectoderm, were isolated at the beginning of gastrulation. After removal of the
      epithelial layer, explants were maintained in modified Danilchik's medium until
      mid-neurula stages, when they were transferred to modified Danilchik's medium +
      0.1% bovine serum albumin and cultured on laminin. Neurite outgrowth occurred in
      90% of these planar explants. In contrast, little or no neuronal differentiation
      occurred in either ventral planar explants or explants of ectoderm alone. Video
      analysis of cell movements shows that large-scale cell mixing does not occur
      between mesoderm cells and ectoderm cells in planar explants. Retrograde
      labelling of neuronal cell bodies indicates that cells throughout the ectoderm
      undergo neuronal differentiation; neurons also differentiate in cultures of
      distal ectoderm isolated at early neurula stages from planar explants prepared at
      the beginning of gastrulation. These observations indicate that planar signals
      act over an extended range to induce neuronal differentiation. The inductive
      capacity of vertical signals was examined by recombining animal caps from ultra
      violet (UV) irradiated embryos with involuted mesoderm from normal midgastrula
      embryos. Differentiation of either neurons or anterior neural structures occurred
      in 73% of vertical recombinates. Our results demonstrate that planar signals from
      the dorsal lip of the blastopore are capable of inducing neuronal differentiation
      over a considerable distance in the absence of epithelial confinement,
      convergence and extension, and mixing between the mesoderm and ectoderm.

PMID- 8292825
TI  - Localisation of transforming growth factor beta 1 in developing muscles:
      implications for connective tissue and fiber type pattern formation.
AB  - Skeletal muscles are highly ordered mixtures of cell types, with each muscle
      having its own characteristic pattern of fiber types, connective tissues, and
      vasculature. The precursors of the myogenic and connective elements of a muscle
      are initially intermixed and are proliferating and differentiating together in a
      manner that generates an ordered array of mature cells. The molecular basis of
      myogenesis is unknown, although in vitro studies have revealed numerous putative
      regulators. The results obtained from in vitro studies are not easily related to
      in vivo myogenesis because of a lack of information about the localisation of the
      putative regulators in developing muscles. The objective of this paper was
      therefore to describe the spatial and temporal distribution of transforming
      growth factor beta 1 (TGF-beta 1), a small peptide that affects cultured
      fibroblasts, myoblasts, and vascular endothelial cells. TGF-beta 1
      immunoreactivity was associated with the epimysia, perimysia, and vasculature of
      the developing muscles. The expression of TGF-beta 1 within developing muscles
      had a distinct spatial and temporal pattern that correlated with the fate of
      adjacent myotubes. Myotubes which formed prior to the expression of TGF-beta 1
      developed into slow fibers whereas those which formed adjacent to TGF-beta 1
      containing connective tissue matured into fast fibers. The possibility that TGF
      beta 1 is involved in the generation of the pattern of epi- and perimysia and/or
      fiber types is discussed.

PMID- 8292826
TI  - Second messenger regulation of occlusion of the spinal neurocoel in the chick
      embryo.
AB  - We know that, once rostral neurulation is completed in the neuroaxis of the chick
      embryo, the caudal neurocoel becomes occluded and the brain rapidly expands.
      However, very little is known about the mechanisms maintaining occlusion. Studies
      had shown that occluded neurocoels reopened in embryos treated with chelators of
      cations, but the reasons remained unclear and the cations unidentified. To begin
      defining the role of cations, this study explored the effect of Ca2+, calmodulin,
      and cAMP on maintaining the occluded neurocoel. Chick embryos during the natural
      phase of neurocoel occlusion (stage 12) were cultured in vitro with drugs known
      to modulate Ca2+ transport, to inhibit calmodulin activity, or to elevate cAMP
      levels. To test if occlusion is a Ca(2+)-dependent process, embryos were treated
      with verapamil and ionophore A23187. To test if occlusion requires calmodulin,
      embryos were treated with antipsychotic agents. To test if occlusion is cAMP
      dependent, embryos were treated with methylisobutylxanthine (MIX), forskolin
      (FOR), or dibutyl cyclic adenosine (DbC). Following each treatment, occlusion of
      the neurocoel was tested by injecting dye into the midbrain. All treatments
      resulted in a predominant number of precocious reopenings of the occluded
      neurocoels. MIX-treated, naked neural tubes had a four-fold increase in cAMP,
      whereas FOR- and DbC-treated neural tubes showed ten- and 14-fold increases,
      respectively. The presence of calmodulin in the cells of the neural tube was
      confirmed by fluorescent tagging and 3H-chlorpromazine labelling. The combined
      results of this study show that occlusion of the spinal neurocoel depends on
      exogenous Ca2+, requires calmodulin, and is cAMP sensitive.

PMID- 8292827
TI  - Developmentally regulated and spatially restricted antigens of radial glial
      cells.
AB  - Radial glial cells, present in many parts of the embryonic vertebrate central
      nervous system (CNS), have been implicated in the guidance of neuroblasts from
      the ventricular zone to their laminar destinations. Moreover, radial glial cells
      may be progenitors of some CNS neurons and glia. To gain new insight into the
      structure and development of these cells, we have generated and characterized a
      panel of monoclonal antibodies that recognize radial glial cells of the chick
      optic tectum. Mice were immunized with homogenates of embryonic day (E) 10
      tectum, and antibodies were analyzed by immunofluorescence and immunoblotting. We
      describe here three pairs of antibodies. 1) H5 and a previously generated
      antibody, R5 (Drager et al., J. Neurosci. 4:2025, 1984), stain the whole extent
      of the radial glial cell from E7 to E20. In cultures prepared from E10 tecta,
      both stain a filamentous meshwork in glial cells but not in neurons. On
      immunoblots, both recognize a protein of approximately 52 kD that is closely
      related (or identical) to vimentin. 2) H28 and H29 stain radial glia between E7
      and E14, but not later. Moreover, H28 and H29 staining is markedly more intense
      in the ventricular and intermediate zones than in the laminae of the tectal
      plate. Both of these antibodies recognize an intracellular epitope in cultured
      glial cells and a protein of approximately 35 kD on immunoblots. 3) H2 and H27
      recognize antigens concentrated in the most superficial processes and endfeet of
      radial glia in late (E16-E20) embryos. They stain distinct structures in cultured
      glia, suggesting that they recognize distinct antigens. H27 recognizes a protein
      of approximately 29 kD on immunoblots. Thus antibodies H5 and R5 are good markers
      of radial glial cells at all stages, whereas the others define antigens that are
      developmentally regulated and localized to discrete domains. Together, these
      antibodies can be used to study temporal and spatial specializations of radial
      glia.

PMID- 8292828
TI  - Gene expression of CD24 core peptide molecule in developing brain and developing
      non-neural tissues.
AB  - CD24 is a signal transducing molecule on the surface of most human B cells,
      murine immature T cells, myeloid and erythroid lineage cells. We isolated rat
      CD24 gene from embryonic brain cDNA library and characterized the gene expression
      during rat embryogenesis. Rat CD24 cDNA is homologous to murine and human CD24
      gene with respect to the structure of signal peptide, N-glycosylation sites, and
      possible glycosyl phosphatidylinositol (GPI) linker attaching site, suggesting
      that rat CD24 is a transducing glycoprotein anchoring membrane via GPI linker. In
      the developing embryo, in situ hybridization analyses revealed that CD24
      transcript was detected in primitive ectoderm, mesoderm, and ventral endoderm of
      day 9 postcoitum (p.c.) embryo. In central nervous systems CD24 transcript was
      strongly expressed in postmitotic cells of spinal cord, hindbrain, midbrain, and
      forebrain from day 11 p.c. embryo to day 21 p.c. embryo but was dramatically down
      regulated in adult brain. Furthermore, expression was also detected in epithelium
      during development of non-neural tissues, such as intestinal mucosal epithelium,
      nasal epithelium, ductal epithelium of salivary gland, bronchial epithelium,
      renal tubular epithelium, and hair follicles. In tooth development, where correct
      epithelium requires epithelial-mesenchymal interactions, CD24 mRNA was
      specifically induced in mesenchymal cells differentiating into odontoblast in
      dental papilla, suggesting the pivotal role of CD24 molecule in cell
      differentiations in vivo. We suggest that CD24 gene may encode the core peptide
      molecule of 31 kDa GPI linked molecule which has been known to be important in
      the migration of neurons on astroglial processes during development.

PMID- 8292830
TI  - Effect of epidermal growth factor on expression of transforming growth factor
      beta 1 mRNA in stellate reticulum cells of rat mandibular molars.
AB  - Cultured stellate reticulum cells isolated from rat mandibular molars respond to
      incubation in EGF by increasing their level of expression of TGF-beta 1 mRNA.
      Northern blots showed that incubation in EGF for 6 hours stimulated over a two
      fold increase in TGF-beta 1 mRNA in the cells. In contrast, incubating the cells
      in TGF-beta 1 did not enhance the expression of TGF-beta 1 mRNA in the cells,
      indicating that TGF-beta 1 does not have an autocrine effect on these cells.
      Immunocytochemistry showed that EGF receptor was present on the surface of many
      but not all of the cultured stellate reticulum cells. Because EGF does stimulate
      premature eruption of teeth, it is possible that its effect on the stellate
      reticulum region of the enamel organ would be to stimulate synthesis of TGF-beta
      1 mRNA which, in turn, could lead to increased synthesis of TGF-beta 1 by these
      cells. The cells do contain the TGF-beta 1 protein as revealed by
      immunocytostaining. The newly synthesized TGF-beta 1 may exert its effect on the
      adjacent dental follicle to either initiate the onset of the cellular events of
      tooth eruption or to increase the secretion of extracellular matrix proteins by
      the follicle for formation of the periodontal ligament.

PMID- 8292829
TI  - Selective expression of the chicken platelet-derived growth factor alpha (PDGF
      alpha) receptor during limb bud development.
AB  - Platelet-derived growth factor (PDGF) affects proliferation and differentiation
      of chicken limb bud mesoderm in vitro. However, no PDGF receptor has been
      characterized in the chicken wing bud in vivo. In this study, we used reverse
      transcription PCR (rtPCR), Northern blot analysis, and Western blot analysis to
      identify a molecule, in the developing wing bud, which represents the chicken
      homolog of the PDGF alpha receptor. The chicken PDGF alpha receptor mRNA was
      present in both mesoderm and ectoderm and all stages of the developing limb bud
      examined. Cultured limb bud mesoderm also expressed the PDGF alpha receptor
      transcript. In addition, the PDGF alpha receptor protein was present in whole
      limb buds and cultured limb bud mesoderm. Expression of the PDGF alpha receptor
      in cultured mesoderm was independent of the presence of ectoderm cells. The
      relative sizes of both the mRNA and protein for the PDGF alpha receptor in the
      chicken limb bud were similar to mammalian counterparts. Using similar
      approaches, neither the mRNA nor protein representing the chicken homolog of the
      PDGF beta receptor was detected. These data demonstrate for the first time that a
      PDGF alpha receptor is present in the embryonic chicken limb bud and may help
      regulate growth and differentiation of the embryonic limb.

PMID- 8292831
TI  - Proportion of proliferative cells in the tadpole retina is increased after
      embryonic lesion.
AB  - Little is known about the cellular mechanisms that cause some cells to stop
      dividing while leaving neighboring cells free to continue dividing. Such events
      occur during development of the Xenopus retina; all cells of the embryonic eyebud
      are mitotic, but by stage 37 (St 37), only cells at the ciliary margin continue
      to proliferate as neighboring cells become post-mitotic. The mechanisms that
      control these different proliferative fates remain unknown. One possibility is
      that total cell number regulates the initial number of proliferative cells at the
      ciliary margin. To test this hypothesis, we reduced the cell number by surgically
      removing a portion of the embryonic eyebud, including part of the prospective
      proliferative zone. Cell counts confirmed that the numbers of both the mitotic,
      undifferentiated cells and the post-mitotic, differentiated cells were reduced
      following the partial ablation. A regression analysis suggested that the initial
      number of undifferentiated cells was a fixed proportion of the total number, but
      that this proportion was increased by the partial ablation. This increase
      occurred for all stages that the partial ablation was performed, from early optic
      vesicle to mid optic cup stages. The proportion of undifferentiated cells was
      normal in sham-operated retinas, indicating that the increase in partially
      ablated retinas was induced by tissue removal and not by wound healing. Analyses
      of clones derived from single precursors, labeled with a fluorescent lineage
      tracer, indicated that the rate of proliferation was the same in partially
      ablated and sham-operated retinas. Measurements of bromodeoxyuridine
      incorporation directly confirmed that at the ciliary margin cell division time
      was unchanged after partial ablation. Our observations are most consistent with
      the hypothesis that the proportion of undifferentiated cells was increased
      because cells that would have become post-mitotic remained proliferative after
      the partial ablation. Furthermore, cell-cell interactions most likely play a
      major role in controlling the initial number of proliferative cells in the
      tadpole retina.

PMID- 8292832
TI  - Raphe of the posterior neural tube in the chick embryo: its closure and reopening
      as studied in living embryos with a high definition light microscope.
AB  - Chick embryos cultured on a curved substratum show a transient enlargement of the
      posterior neuropore (PN), mimicking the temporary delay of PN closure as seen in
      the curly tail (ct) mouse mutant (van Straaten et al. [1993] Development 117:1163
      1172). In the present study the PN enlargement in the chick embryo was
      investigated further with a high definition light microscope (HDmic), allowing
      high resolution viewing of living embryos in vitro. The temporary PN enlargement
      appeared due to considerable reopening of the raphe of the posterior neural tube,
      which was followed by reclosure after several hours. The raphe was subsequently
      studied in detail. It appeared very irregular, with small zones of apposed, open
      and fused neural folds. During closure, these raphe features shifted posteriorly.
      A distinct fusion sequence between surface epithelium and neuroepithelium was not
      seen. During experimental reopening of the raphe in vitro, small bridges
      temporarily arose, broke and disappeared quickly; they likely represented the
      first adhesion sites between the neural folds. More prominent adhesion sites
      partly detached, resulting in bridging filopodia-like connections; they probably
      represented the first anteroposterior locations of neural fold fusion. Our
      observations in the living chick embryo in vitro thus show that the caudal neural
      tube has an irregular raphe with few adhesion sites, which can be readily
      reopened. As a result of the irregularity, the PN does not close zipper-like, but
      button-like by forming multiple closure sites.

PMID- 8292833
TI  - An experimental study of the placebo effect in African traditional medicine.
AB  - In an experimental study on the placebo effect in Malawi, an independent East
      African nation, 21 Malawian college students were tested individually in two 1
      hour sessions on successive afternoons, using a one-group, two-condition before
      after counterbalanced experimental design. Subjects were falsely told that a
      physiologically neutral substance they consumed would arouse the body, affecting
      oral temperature and pulse. Before-after measurements were taken during each
      day's session. On one of the days, the placebo resembled a traditional African
      herbal concoction, whereas on the other day, the placebo appeared to be a
      commercial Western-style medicine. The placebo effect was evaluated for each
      medication by comparing pre- and posttreatment scores. After the session, the
      subjects completed a questionnaire on their beliefs in the power of each style of
      medication. The placebo response was demonstrated in both medication conditions
      for oral temperature, but the strength of the placebo effect did not vary between
      medication styles. No significant relationship was found between the placebo
      effects and self-reported attitudes toward the two types of medication.

PMID- 8292834
TI  - Emotional crying, depressed mood, and secretory immunoglobulin A.
AB  - The relationship between emotional crying and secretory immunoglobulin A (S-IgA)
      in whole saliva was examined. Previous research had indicated that lower S-IgA
      was associated with crying. Similar results were found in the present study.
      Depressed mood was not associated with S-IgA.

PMID- 8292835
TI  - Relationship between family environment and children's hemodynamic responses to
      stress: a longitudinal evaluation.
AB  - Because interpersonal relationships may have an impact on the risk of developing
      cardiovascular disease, the authors examined the prospective relationship of
      family functioning upon hemodynamic stress responses in 87 6- to 8-year-old
      children. The parents completed the cohesion, conflict, expressiveness, and
      control subscales of the Family Environment Scale; 2 years later, the authors
      assessed the children's hemodynamic responses to postural change, forehead cold
      stimulation, and treadmill exercise. Maternal reports of greater cohesion and
      expressiveness were related to less increases in systolic pressure and systemic
      vascular resistance in response to the forehead cold. Mothers' reports of
      expressiveness were related to lower systolic pressure and cardiac index
      reactivity to postural change. Fathers' reports of greater control were
      associated with greater diastolic pressure and vascular resistance increases to
      forehead cold and to greater vascular resistance responses to exercise. Paternal
      reports of greater conflict were associated with greater systemic vascular
      resistance increases and with lower cardiac index increases to exercise. Results
      suggest family functioning may predict later hemodynamic reactivity to stress.
      The findings are discussed in terms of previous research on parent-child
      interaction patterns and children's cardiovascular health.

PMID- 8292836
TI  - Effects of demand and decision latitude on cardiovascular reactivity among
      coronary-prone women and men.
AB  - According to the Job Strain Model, high demand/low decision latitude jobs may be
      associated with increased risk of developing coronary heart disease. In further
      analyses of a laboratory study, the authors hypothesized that Type A behavior
      and/or hostility moderate the effects of demand, decision latitude, and gender on
      cardiovascular reactivity, a putative mechanism for the development of coronary
      disease. With multiple regressions, it was found that scores on the Framingham
      Type A scale interacted with demand and decision latitude to affect diastolic
      blood pressure changes, such that Type Bs in the low demand/high decision
      latitude condition showed the smallest increases in diastolic blood pressure.
      Among men, hostility accounted significantly and positively for variance in
      systolic blood pressure changes in addition to that accounted for by high demand.
      These results suggest that coronary-prone traits may potentiate, or add to, the
      effects that stressful environments have on health outcomes.

PMID- 8292837
TI  - The relationship between daily stress and urinary cortisol in a normal
      population: an emphasis on individual differences.
AB  - Twenty-three persons participated in a study examining the relationship between
      daily stressors and daily fluctuations in cortisol. For 21 days, the participants
      completed the Assessment of Daily Experience scale, which yielded frequency and
      intensity stress scores and gave an indication of the subjects' perceptions of
      their control over the daily stressors. Nightly urines were collected and assayed
      for cortisol. The prospective design of the research allowed the authors to
      examine individual differences in cortisol over time as well as the often-studied
      pooled differences. Results from pooled and individual data showed that the
      intensity of the worst daily stressor was a significant but modest predictor of
      daily cortisol. The authors concluded that the relationship between cortisol and
      psychological events for pooled data is small because of the wide variability in
      individual responses.

PMID- 8292838
TI  - Victims of the intifada: the psychosocial adjustment of the injured.
AB  - This empirical study assessed the psychosocial adjustment of the Palestinians who
      sustained serious bodily injuries during the intifada. Research dealt with the
      personal and interpersonal forces that impede or facilitate adjustment, with the
      mediating effect of social support and with the special services provided by
      local institutions. Findings suggested that a lapse of time did not improve
      adjustment. The level of education and marital status had an apparent effect on
      adjustment. An individual's adjustment correlated positively with situational
      variables, whereas it was negatively affected by trauma-related variables.
      Implications for future research, coping strategies, and rehabilitation plans are
      discussed.

PMID- 8292839
TI  - Comparison of the radiographic vertebral trabecular pattern with the vertebral
      fracture prevalence and spinal bone density.
AB  - Spinal bone densitometry allows accurate and precise measurement of the severity
      of bone loss. Where densitometry is not yet available medical practitioners have
      to continue to rely on clinical radiography. Since the grey levels of the
      radiographic image are highly inaccurate we studied the radiographic vertebral
      trabecular pattern for its suitability as a semiquantitative assessment of
      vertebral bone loss. We defined four vertebral trabecular pattern indices (VTPI 4
      = normal, VTPI 1 = severe bone loss) and tested these for correlations with the
      prevalence of vertebral fractures, and with spinal and hip bone mineral density
      measured by dual-energy X-ray absorptiometry (DXA). We found negative
      correlations between VTPI and the percentage of patients with vertebral fractures
      (p = 0.0001), between VTPI and the number of vertebral fractures per patient (r =
      0.606, p = 0.001) and between VTPI and the severity of vertebral fractures, and a
      positive correlation between VTPI and spinal (r2 = 0.556, p = 0.0001) and hip DXA
      values (r2 = 0.315, p = 0.0001). We conclude that the vertebral trabecular
      pattern index can be used to assess the severity of spinal bone loss when a bone
      densitometer is not available.

PMID- 8292840
TI  - Vertebral deformity, bone mineral density, back pain and height loss in
      unscreened women over 50 years.
AB  - Bone mineral density (BMD) was measured in the lumbar spine using dual-energy X
      ray absorptiometry in 222 unscreened women (aged 50-82 years), and information on
      back pain and historic loss of standing height was obtained at interview.
      Vertebral morphometry was performed on lateral spinal radiographs. The shape of
      the vertebral body was quantified using appropriate vertebral shape indices
      (VSIs), and vertebral deformities were identified using thresholds defined in
      terms of the means (M) and standard deviations (SD) of these VSIs for the whole
      group. Severity of deformity was defined as either grade 1 (M+2SD < VSI < M+3SD),
      grade 2 (M+3SD < VSI < M+4SD or grade 3 (VSI > M+4SD). Subjects with grade 1
      vertebral deformities were older than subjects without such deformities, but did
      not have a reduced age-related Z-score of BMD. Grade 2 wedge and concave
      deformities were associated with a reduced age-related Z-score of BMD, suggesting
      that the aetiology of such deformities is closest to conventional concepts of
      'osteoporotic fracture'. Grade 3 deformities were associated with neither
      increased age nor decreased BMD. Stature decreased in these subjects with age.
      Subjects reporting historic height loss had a higher mean number of wedge
      deformities. Subjects with back pain did not have a higher incidence of vertebral
      deformity than subjects without, confirming that many deformities were
      asymptomatic. Neither back pain nor historic loss of height were found to be
      associated with low spinal BMD.

PMID- 8292841
TI  - Velocity of ultrasound at the patella: influence of age, menopause and estrogen
      replacement therapy.
AB  - Determination of apparent velocity of ultrasound (AVU) in bone has been proposed
      as a valuable tool for discriminating between normal and osteoporotic women. We
      have studied the influence of age, menopause and estrogen replacement therapy
      (ERT) on AVU at the patella in a large sample of pre- and postmenopausal women.
      Three hundred and eighteen woman aged 40-60 year participated in the study (112
      women were premenopausal, 21 were perimenopausal and 185 were postmenopausal of
      whom 110 had received ERT for a minimum of 1 year). AVU was determined as the
      mean of four measurements at each patella using a Signet instrument (Osteo
      Technology, Framingham, MA). An age-dependent decline in AVU was observed only
      after menopause (r = -0.33, p = 0.0055); in premenopausal women there was a
      slight but not significant decrease in AVU with age (r = -0.12, p > 0.05). AVU
      was significantly lower in postmenopausal women compared with premenopausal women
      (1882 +/- .84 m/s vs 1961 +/- 73 m/s, p < 0.05). ERT prevented the menopause
      related fall in AVU. There was a significant positive correlation between the
      duration of ERT and AVU measurements. Our findings demonstrate a pronounced
      influence of estrogens on AVU at the patella, supporting the concept of a
      protective role of ERT in bone stability. AVU measurements therefore merit
      further investigation as an inexpensive method for predicting fracture risk that
      does not expose the subject to radiation.

PMID- 8292842
TI  - Body size, estrogen use and thiazide diuretic use affect 5-year radial bone loss
      in postmenopausal women.
AB  - Understanding factors associated with more rapid bone mineral loss among aging
      women is important for establishing preventive strategies for intervention. This
      study reports factors associated with the 5-year change in radial bone mineral
      density (BMD) determined prospectively in 435 women aged 55-80 years at baseline.
      The baseline study included measurement of radial BMD (gm/cm2) by single photon
      densitometry and personal interview. The baseline protocol was replicated 5 years
      later in a follow-up study. Women with a lower baseline weight or Quetelet index,
      smaller triceps skinfold and less arm muscle area had significantly greater 5
      year bone loss (p = 0.001). Current users of estrogens had less radial bone loss
      (2.8% vs 7.3%, p = 0.0005) than women not currently using estrogens. Current
      users of estrogen had significantly less 5-year loss if use had been for 5 years
      or longer (-1.0% vs -6.9%, p = 0.05). Current users of the thiazide class of
      medications had less 5-year radial bone loss (5.0% vs 7.4%, p = 0.0035) than
      women without current thiazide use. Baseline dietary calcium, alcohol consumption
      and smoking were not associated with BMD change. This suggests that greater body
      size, and current use of estrogens or thiazide antihypertensives are associated
      with less radial bone mass loss in a 5-year period among postmenopausal women.

PMID- 8292843
TI  - Bone loss after cardiac transplantation: effects of calcium, calcidiol and
      monofluorophosphate.
AB  - Of 203 patients who underwent cardiac transplantation and were given long-term
      treatment with cyclosporine and 0.3 mg/kg per day prednisone, 123 were studied
      prospectively for at least 6 months and 46 for up to 2 years to evaluate the
      effects on lumbar bone mineral density (BMD) and calcium metabolism of a combined
      therapy with calcium, calcidiol and disodium monofluorophosphate (MFP). The
      population was arbitrarily assigned to one of two groups. Group I consisted of
      patients who had a lumbar spine BMD Z score above -1.5 SD as compared with an age
      and sex-matched population and no vertebral fractures. They received daily 1 g
      elemental calcium and 25 micrograms (1000 IU) calcidiol. Group II consisted of
      patients who received daily the same doses of calcium and calcidiol combined with
      200 mg MFP, and was divided into two subgroups: (a) osteopenic subjects who had a
      lumbar spine BMD Z score below -1.5 SD without vertebral fractures and (b)
      osteoporotic subjects with vertebral fractures. If serum creatinine was higher
      than 140 mumol/l the daily dose of MFP was tapered to 100 mg. Fifty-four and 27
      patients from group I and 38 and 19 patients from group II were followed
      respectively for 12 and 24 months. In both groups serum parathyroid hormone
      levels were significantly reduced from the twelfth month in parallel with a
      significant increase in serum 25-OHD levels. No decline in lumbar BMD occurred in
      non-osteopenic and non-osteoporotic patients (group 1) who received the calcium
      and calcidiol supplement. In group II, where MFP was added, a significant and
      linear increase in lumbar BMD was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292844
TI  - Human growth hormone and growth hormone releasing hormone: a double-masked,
      placebo-controlled study of their effects on bone metabolism in elderly women.
AB  - We treated 42 postmenopausal women with decreased bone mass for 12 weeks with
      human growth hormone, growth hormone releasing hormone, or placebo. Bone density
      and biochemical markers were determined before and during treatment, and 4 weeks
      after withdrawal. Biochemical markers of bone formation and resorption increased
      significantly in the group treated with growth hormone, whereas no changes were
      seen in the other groups. After withdrawal of therapy the bone markers declined
      without reaching baseline values. Bone density in the forearm, spine and proximal
      femur was unchanged in all groups. We conclude that treatment with growth hormone
      stimulates bone metabolism in elderly postmenopausal women with decreased bone
      mass.

PMID- 8292845
TI  - The effect of short-term calcitonin administration on biochemical bone markers in
      patients with acute immobilization following hip fracture.
AB  - The effect of salmon calcitonin on changes in mineral metabolism was studied in
      40 elderly patients with recent hip fracture. All patients underwent surgery
      (internal fixation) 1 week after admission and were randomly divided into two
      equal groups: group A, which received no treatment, and group B, which received
      100 IU/day salmon calcitonin intramuscularly for 2 weeks starting on admission.
      Blood and 24-h urine parameters of mineral metabolism were measured on admission
      and at the end of weeks 1 and 2. No intra- or intergroup changes in serum
      calcium, phosphorus or alkaline phosphatase were observed. At the end of week 2
      biochemical markers of bone resorption (urinary calcium and hydroxyproline) had
      significantly increased in group A and significantly decreased in group B,
      indicating a reduction in bone resorption in group B. Urinary phosphorus had also
      increased in group B, possibly due to the phosphaturic effect of calcitonin. It
      is concluded that immobilization resulting from a hip fracture, and possibly
      surgery itself, causes significant changes in biochemical markers of bone
      resorption. Calcitonin successfully reverses these changes and may also be
      effective in preventing subsequent bone loss, particularly in patients who cannot
      be remobilized immediately.

PMID- 8292846
TI  - The effect of high sodium intake on bone mineral content in rats fed a normal
      calcium or a low calcium diet.
AB  - The effect of high sodium intake on bone mineral content of rats fed a normal
      (0.6% Ca) or a low (0.02% Ca) calcium diet was studied. Rats on a normal calcium
      diet given 1.8% sodium chloride to drink showed persistent and significant
      hypercalciuria and subnormal bone mineral content. Total calcium content of femur
      was significantly lower after 4 months (p < 0.02) and 12 months (p < 0.001). In
      rats maintained on a low calcium diet (0.02% Ca), a high sodium diet for 8 weeks
      caused a significant loss of calcium in bone similar to that seen in animals fed
      a normal calcium diet for 4 months. We conclude that high sodium intake reduces
      bone mineral content, especially if the diet is low in calcium.

PMID- 8292848
TI  - Bradykinin analogs as inhibitors of angiotensin-converting enzyme.
AB  - A series of peptide analogs and fragments of bradykinin were designed and
      synthesized on solid supports using Boc and Fmoc strategies, and on polyethylene
      pins using Fmoc strategy. The peptides were purified, characterized and tested
      for their inhibitory effects on angiotensin-converting enzyme. The inhibition of
      the converting enzyme. The inhibition of the enzyme was measured
      spectrophotometrically using Furylacryloyl-Phe-Gly-Gly as the substrate. Apparent
      Ki's were determined for the substrates, which exhibited significant inhibition
      in the initial screening assay using 10 microM of the peptide inhibitor. Short
      peptides corresponding to the carboxyl terminus of bradykinin were found to be
      poor inhibitors of angiotensin-converting enzyme. However, bradykinin-like
      peptides with modifications at their amino terminus are effective inhibitors. The
      best inhibitor found in this study, Ala2,6-des-Pro3-bradykinin, has an apparent
      Ki of 30.2 nM, compared to an apparent Ki of 94 nM for des-Pro3-bradykinin, which
      was reported to be a better inhibitor of angiotensin-converting enzyme than
      captopril.

PMID- 8292847
TI  - Conformationally constrained formyl methionyl tripeptides: structure-function
      study of analogs containing alpha,beta-dehydrophenylalanine and dehydroleucine.
AB  - In order to probe the role of peptide backbone conformation on the biological
      activity of chemotactic peptides through conformationally constrained peptides,
      we synthesized the following three analogs of N-formyl-Met-Leu-Phe-OH (fMLF)
      containing dehydrophenylalanine (delta ZPhe) and dehydroleucine (delta ZLeu):
      formyl-Met-delta ZPhe-Phe-OCH3 (1), formyl-Met-delta ZLeu-Phe-OCH3 (2) and formyl
      Met-delta ZPhe-delta ZPhe-OCH3 (3) and studied their conformational behavior in
      solution by 1H NMR and IR spectroscopy. The conformation of (1) was also examined
      by x-ray diffraction methods. Biological activity of these analogs was assessed
      for their ability to induce the release of beta-glucosaminidase from rabbit
      neutrophils. In addition, the chemotactic activity of analog (2) was also
      determined. We found that, in the solid state, (1) favors a type II beta-turn
      structure, stabilized by a 4-->1 intramolecular hydrogen bond. A similar
      structure was reported recently for (2) also. 1H NMR studies in solution suggest
      that the Phe NH is solvent shielded in both (1) and (2) and that a major
      population of peptide molecule exists in an intramolecular hydrogen bond
      stabilized type II beta-turn conformation. None of the NH groups in (3) and
      another analog, formyl-Met-Phe-Phe-OCH3 (4), appear solvent shielded, favoring an
      extended structure for these analogs. Analogs (2) and (4) are highly active
      indicating that both extended and beta-turn backbone conformations may be
      compatible with high activity and that the phenylalanine ring in the middle
      position is well accepted. Highly reduced activities of (1) and (3) suggest that
      delta ZPhe residue in position 2, irrespective of the preferred peptide backbone
      conformation, is not acceptable for high bioactivity. These results suggest that
      an induced fit mechanism may possibly be the most relevant one, but the nature
      and the topography of the side chains, particularly the middle residue, may be
      crucial for appropriate receptor ligand interactions.

PMID- 8292849
TI  - Solid-phase synthesis of a peptide-ligand affinity matrix for isolation of
      chymosin.
AB  - Aminopropyl Perloza beaded cellulose was used as the support for solid-phase
      synthesis of resin-bound Val-dLeu-Pro-Phe-Phe-Val-dLeu, an inhibitor of aspartic
      proteases. Both Boc and Fmoc SPPS methodologies were employed in separate
      syntheses. The peptide-resins were characterized by amino acid analysis. The
      peptide-resin from the Fmoc synthesis gave the better amino acid analysis of the
      two syntheses and was used for further studies. Following modification of the
      peptide N-terminus by succinylation, the peptide-resin was able to bind chymosin
      (E.C. 3.5.21.4). The peptide resin was used for isolation of chymosin from a
      crude recombinant broth.

PMID- 8292850
TI  - Synthesis of large multideterminant peptide immunogens using a poly-proline beta
      turn helix motif.
AB  - We report the synthesis and characterization of a novel secondary structural
      motif, the poly-proline beta-turn helix. This motif is found in the proline-rich
      immunogenic domains of feline retroviruses, mucins and many proline-rich tandem
      repeat-containing surface proteins. We describe the synthetic methodology to
      directly synthesize natural and engineered immunogens of up to 100+ amino acids.
      Using manual solid-phase peptide synthesis modified for optimal efficiency, we
      directly synthesized 1, 2, 3, 4 and 5.25 tandem repeats corresponding to 20, 40,
      60, 80, 105 amino acids of the human mucin muc-1, the complete 60 amino acid
      proline-rich neutralization domain of feline leukemia virus, and 70 and 72 amino
      acids of two very hydrophobic engineered tandem repeat proteins. High pressure
      liquid chromatography and mass spectrometry results indicate that the desired
      peptide can be synthesized up to 92% pure. The secondary structures of these
      peptides were studied using circular dichroism (CD) spectroscopy. The CD spectra
      revealed a characteristic intense negative band at 198 nm. A melting of structure
      could be demonstrated with increasing temperature as measured by decreasing molar
      ellipticity at 198 nm. The intensity of the molar ellipticity at 198 nm, as
      compared to the molar ellipticity of random coil, non-proline-containing
      peptides, led to the conclusion that the large, intense negative band at 198 nm
      is diagnostic of the poly-proline beta-turn helix.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8292851
TI  - Continuous-flow solid (gel)-phase peptide synthesis using unsupported ultrahigh
      load polymers: Fmoc/t-butyl strategy.
AB  - The technique of continuous-flow solid-phase peptide synthesis using unsupported
      polymers has been extended to cover the use of N alpha-Fmoc protected amino
      acids. This approach to peptide synthesis uses (but is not limited to) a phenolic
      bead-form polymer at 5 mmol g-1 loading. The success of the technique is based
      upon "layered displacement" to efficiently remove spent reagents and washing
      solutions from within the flow reactor under low pressure conditions. This system
      has been successfully employed in synthesizing the test peptides, [Leu5]
      enkephalin, neurotensin and the notoriously difficult decapeptide sequence (65
      74) of the acyl carrier protein.

PMID- 8292852
TI  - Optimization of peptide synthesis on polyethylene rods.
AB  - Multipin solid-phase peptide synthesis is widely used for epitope mapping of
      monoclonal and polyclonal antibodies. However, neither the chemical yield nor the
      homogeneity of products currently match those of solid-phase synthesis of
      peptides on resins. In order to improve synthesis parameters, we have repeated
      the standard procedure and introduced modifications during synthesis of model
      heptapeptides and peptides from the sequence of rhodopsin and other proteins.
      Good incorporation of amino acids using the multipin peptide synthesis system can
      now be obtained in less synthesis time and with less costly reagents.

PMID- 8292853
TI  - Pin peptide synthesis.

PMID- 8292854
TI  - Paraplegia due to osteitis fibrosa secondary to primary hyperparathyroidism:
      report of a case.
AB  - A case of primary hyperparathyroidism associated with osteitis fibrosa cystica
      presenting as paraplegia is described herein. The symptom complex of
      normocalcemic hyperparathyroidism with osteitis fibrosa cystica is a distinctly
      rare entity and to the best of our knowledge, this is the first case report of
      the normocalcemic variant of primary hyperparathyroidism presenting with
      paraplegia as a complication.

PMID- 8292855
TI  - Decrease in aortic distensibility after an extended aortic reconstruction for
      Marfan's syndrome as a cause of postoperative acute aortic dissection DeBakey
      type I: a report of two cases.
AB  - Two cases of Marfan's syndrome underwent a reconstruction of the abdominal aorta
      and descending thoracic aorta. A replacement of the abdominal aorta with visceral
      arteries as well as a wrapping of the descending thoracic aorta was performed in
      case 1 while a reconstruction of the descending thoracic aorta and infra-renal
      abdominal aorta was done in case 2. After the reconstruction, both cases
      developed acute aortic dissection DeBakey type I. Another reconstruction of the
      ascending aorta was then urgently performed. Cardiac catheterization after the
      second operation in case 1 revealed that the distensibility of the aorta had
      disappeared at the location of the vascular prosthesis while it had also
      decreased at the wrapped portion, and the maximum dp/dt of the ascending aorta
      also increased. Increases in the pulse pressure and pulse rate after the first
      operation were observed in both cases. These hemodynamic changes, which were
      produced by a decreased distensibility of the reconstructed aorta, increased the
      mechanical stress to the native aortic wall, and may have been one of the causes
      of acute aortic dissection DeBakey type I occurring after reconstruction with a
      prosthesis.

PMID- 8292856
TI  - Successful right common iliac to superior mesenteric artery bypass for mesenteric
      ischemia associated with acute aortic dissection: report of a case.
AB  - Mesenteric ischemia caused by obstruction of the superior mesenteric artery
      associated with acute aortic dissection was successfully treated by surgery in a
      74-year-old man. The vein graft was effectively bypassed between the right common
      iliac artery and superior mesenteric artery on the day of onset of acute DeBakey
      type III b aortic dissection. He is currently well 1 year postoperatively on anti
      hypertensive therapy.

PMID- 8292857
TI  - Radical resection of primary malignant melanoma of the gallbladder with multiple
      metastases: report of a case.
AB  - We present herein an usual case of primary malignant melanoma of the gallbladder
      in a 51-year-old man in whom an exploratory laparotomy for melena revealed six
      malignant melanoma lesions located in the gallbladder, main pancreatic duct,
      stomach, duodenum, jejunum, and a mesenteric lymph node. Total pancreatectomy was
      performed and histologically, junctional activity was seen only in the
      gallbladder, suggesting that this was the primary site. No melanotic lesions were
      found on the skin or eyes. The metastases to the main pancreatic duct and
      gastrointestinal tract appeared likely to have occurred as a consequence of the
      mucosal dissemination of the tumor cells shed into the bile. The post-operative
      course was uneventful and combined chemotherapy was administered for 16 months.
      No new metastatic lesions were found until 21 months postoperatively, when
      metastases were detected in the brain and thoracic spinal cord. These metastatic
      tumors were removed surgically, but the patient died from cerebral disturbance 26
      months after the initial operation. Thus, we consider that aggressive surgical
      therapy was effective for extending the survival time and improving the quality
      of life of this patient.

PMID- 8292858
TI  - Long-term total parenteral nutrition and osteoporosis: report of a case.
AB  - A patient who had been supported with total parenteral nutrition (TPN) for over 8
      years is herein presented, with emphasis on the changes observed in calcium
      metabolism. The patient was a 31-year-old female, who had undergone a subtotal
      jejunal and ileal resection for superior mesenteric artery occlusion. TPN was
      started soon after the surgery. She had been on TPN support for 105 months. Back
      pain developed at 97 months after the initiation of TPN. During her course, the
      serum calcium levels were judged to be within the normal ranges, while the 1
      alpha, 25(OH)2Vit.D declined. Intermittent hypercalciuria was occasionally
      observed. Both the serum level of calcium and urinary calcium loss correlated
      closely to the amount of calcium infused, but they were not influenced by the
      amount of vitamin D (ergocalciferol) received. The serum level of parathormone
      and calcitonin were also within the normal ranges. The patient's vertebral bone,
      which was obtained at autopsy, revealed histopathological changes characteristic
      of osteoporosis. Based on the above, we conclude that a careful monitoring of the
      amount of calcium infused is called for to prevent bone disease in patients on
      long-term parenteral nutrition.

PMID- 8292859
TI  - Kumacone II: an adapter to aid in the placement of a purse-string suture in very
      low anterior rectal resection.
AB  - We have designed an adapter called the "Kumacone II", being a bottle-shaped
      rubber device which greatly aids in placing a purse-string suture, even at the
      lowest level near the anorectal junction of the rectum. When this adapter is
      used, performing the anastomosis is much less time-consuming and not as much
      training is needed as for low anterior resection using conventional manual
      suturing. In a clinical study, the incidence of leakage and incontinence was nil
      in five out of five patients.

PMID- 8292860
TI  - Esophago-jejuno-duodenal anastomoses with an ultra-short duodenum.
AB  - Reconstruction following total gastrectomy usually requires one of the various
      methods of esophagojejunal anastomosis. We present herein the case of a 78-year
      old woman with gastric carcinoma involving the adjacent organs for which
      resection of the whole stomach, distal pancreas, transverse colon, and distal
      duodenum was performed. Reconstruction was carried out with an
      esophagojejunostomy, followed by a side-to-side anastomosis between the raised
      jejunal limb and the residual short duodenum. Her postoperative course was
      uneventful and she was able to lead a relatively comfortable life at home until
      she died after tumor recurrence caused GI bleeding 1 year postoperatively. This
      new modified Roux-en-Y with an ultra-short duodenum can be applied for such
      contiguously invasive gastric carcinoma to achieve a better quality of life, when
      conventional reconstruction techniques after total gastrectomy are not indicated.

PMID- 8292861
TI  - Methicillin-resistant Staphylococcus aureus infections following esophageal
      surgery in patients with impaired defense mechanisms.
AB  - This study was conducted to determine whether or not compromised host defense
      mechanisms prior to surgery are related to postoperative infections with
      methicillin-resistant Staphylococcus aureus (MRSA). Neutrophil cytocidal
      activities, serum complement and immunoglobulin levels, the in vivo antibody
      producing capacity against pneumococcal polysaccharide (PPS), and cell-mediated
      immunity (CMI) were evaluated in 22 patients who underwent esophagectomy for
      esophageal cancer between 1989 and 1990. Postoperatively, nine patients developed
      MRSA infections. Anti-PPS IgG was found to be significantly lower in patients
      with MRSA infections than in those without (P < 0.01). All the patients with MRSA
      infections showed a titer < 600 EU, while all but one of the non-infected
      patients showed a titer > 600 EU. Impairment in other components of the defense
      mechanisms, apart from a partial deficiency of CMI, did not differ between the
      groups. Thus, a preoperative evaluation of the antibody-producing capacity may
      serve to predict the development of MRSA-related infections following major
      surgery such as esophagectomy.

PMID- 8292862
TI  - Gastric inhibitory polypeptide secretion after gastrectomy in patients with
      diabetes mellitus.
AB  - Gastric inhibitory polypeptide (GIP) secretion after distal gastrectomy was
      compared between patients with diabetes mellitus (DM-group) and patients with
      normal glucose tolerance (N-group). GIP secretion in the DM-group was
      significantly greater in the early postcibal response period, but less in the
      late postcibal response period after gastrectomy, the total secretion of GIP
      being less after gastrectomy than before in this group. In the N-group, both the
      early and total postcibal responses of GIP were greater after gastrectomy than
      before. Moreover, the early and total postcibal secretions of GIP after
      gastrectomy were less in the DM-group than in the N-group. These findings suggest
      that GIP secretion in diabetics becomes insufficient after gastrectomy.

PMID- 8292863
TI  - Transhiatal esophagectomy for esophageal carcinoma in Turkey: with special
      reference to respiratory function.
AB  - Esophagectomy without opening the thoracic cavity--transhiatal esophagectomy-
      (THE) were performed in 47 patients with malignant tumors localized at various
      levels of the esophagus. Pulmonary function studies were performed in all
      patients and they are categorized as low, moderate, or high risk for probable
      postoperative pulmonary complications according to the risk category system. Nine
      of these patients were classified as high risk, seven as moderate risk, and the
      rest as low risk. In all patients but four, reconstruction was accomplished by
      using their stomachs as a substitute. In the remaining patient, intestinal
      continuity was established by a left and right colonic interposition. Three
      patients were lost in the early postoperative period. Two patients categorized as
      low risk died from pulmonary thromboembolism and cardiac failure, respectively.
      One patient categorized in the high risk group died of coronary thrombosis.
      Postoperative complications included transient hoarseness due to recurrent
      laryngeal nerve paresis in one patient, right pleural effusion in one patient,
      pneumothorax in two patients, and thrombophlebitis in one patient. In the high
      risk patient group, there were no pulmonary complications. This clinical study
      demonstrated the protective effect of THE in patients with serious pulmonary
      problems.

PMID- 8292864
TI  - Operative stress potentiates the inductivity of membrane associated lymphotoxin
      (mLT) on lymphokine activated killer (LAK) cells in vitro.
AB  - Membrane-associated lymphotoxin (mLT) is induced in human peripheral blood
      mononuclear cells when cultured with interleukin 2, in the form of lymphokine
      activated killer (LAK) cells. The inductivity of mLT is thought to be dependent
      upon the differentiation potential of LAK cell precursors, being T cells and
      natural killer cells. In this study, we investigated the inductivity of mLT on
      LAK cells from surgical patients. The preoperative values of mLT inductivity were
      found to be generally higher in malignant than benign cases, and the
      postoperative time course of mLT inductivity showed a transient decrease
      immediately after the operation followed by gradual increase over 2 weeks.
      Moreover, patients with an intraoperative bleeding volume of more than 1,000 ml
      showed a delay in the postoperative increase of mLT inductivity. These data
      suggest that operative stress potentiates the inductivity of mLT on LAK cells;
      however, excess stress may cause a delay in the restoration of mLT inductivity.

PMID- 8292865
TI  - Intrahepatic distant metastasis and metachronous multicentric occurrence in
      solitary hepatocellular carcinoma of less than five centimeters in diameter.
AB  - During the 7 years from 1984 to 1990, 36 patients underwent liver resection for
      solitary hepatocellular carcinoma (HCC) measuring less than 5 cm in diameter,
      with no intrahepatic vascular invasion on imaging diagnoses and no macroscopic
      infiltration into the tumor capsule or surrounding tissues. Although HCC is less
      likely to cause intrahepatic adjacent metastasis to the cut liver surface, an
      analysis revealed the possibility of intrahepatic distant metastasis and
      metachronous multicentric occurrences, even after complete removal of the primary
      tumor. The 5-year cumulative survival rate was 53%, while the 5-year cumulative
      recurrence-free survival rate was 19%. Of the 36 patients, 18 (50%) had suffered
      a recurrence by April, 1992, one with extrahepatic metastasis. Recurrence of
      intrahepatic metastasis was multifocal in 5 patients, single and adjacent in 1,
      and single (or a few) and distant in 11. Multifocal recurrence was observed
      within 1 year after liver resection. The sole single and adjacent metastatic case
      occurred in one of eight patients in the recurrent group in whom distance of the
      surgical margin was less than 1 cm [TW(+)]. Multicentric occurrence was found in
      6 of 13 patients (46%) whose recurrent tumors were examined histologically, and
      all belonged to the "single (or a few) and distant" type of recurrence. In this
      report, we also present two typical cases of metastasis, one being multifocal
      metastasis occurring within 3 months after liver resection and the other being
      intrahepatic metastasis occurring after a 4-year-dormant state, to demonstrate
      the complicated nature of the intrahepatic metastatic pattern.

PMID- 8292866
TI  - Quantitative analysis of distribution and fate of human lung cancer emboli
      labeled with 125I-5-iodo-2'-deoxyuridine in nude mice.
AB  - The chemical and radio toxicity of 125-5-iodo-2'-deoxyuridine (125IUDR) on
      870127T human lung cancer (HLC) cells grown in tissue cultures and the
      quantitative analysis of the distribution and fate of 125IUDR-labeled 870127T HLC
      cells in nude mice were evaluated. After 870127T HLC cells were plated and
      125IUDR was added to the dishes at levels ranging from 0.1 microCi/ml to 5.0
      microCi/ml of media, the growth rate of the cells for 24 h was similar to that of
      non-labeled cells. Nude mice were given intravenous injections of 125IUDR labeled
      870127T HLC cells and killed at various intervals ranging from 5 min to 24 h
      after injection. Organs were collected, processed, and monitored. The lung
      contained most of the tumor cells at all intervals and the number of tumor cells
      in the lung decreased gradually post-injection. The tumor cells died rapidly, and
      only about 1.5% of all cell survived after 24 h post-injection. This study
      confirmed that very few surviving tumor cells are needed to cause metastasis.

PMID- 8292867
TI  - Ultrastructural changes in the microvilli as a marker of small bowel rejection.
AB  - Small bowel rejection occurs in patches; therefore, to detect bowel rejection in
      situations where a stomal biopsy appears normal under the light microscope, we
      studied the ultrastructural changes in bowel microvilli following heterotopic
      small bowel transplantation in rats. Thin sections of bowel biopsy specimens,
      which appeared normal under a light microscope, were selected and examined under
      an electron microscope for microvillous changes. Microvillous changes were seen
      in both the syngeneic and allogeneic groups on the 2nd and 4th postoperative
      days, but these changes were absent in the syngeneic group by the 8th
      postoperative day, although they were still detected in the allogeneic group.
      Thus, following small bowel transplantation, electron microscopic analysis is
      recommended to confirm rejection with a patchy distribution after the 8th
      postoperative day.

PMID- 8292868
TI  - Intestinal ischemia resulting from Buerger's disease: report of a case.
AB  - A 42-year-old man who had undergone below-the-knee amputations for Buerger's
      disease 9 and 14 years earlier required emergency surgery for intestinal ischemia
      caused by arterial occlusive lesions in the mesentery. The cecum and proximal
      part of the ascending colon were resected, and marked hyperemic thickening of the
      wall and severe fibrous adhesions were found. Postoperative angiography revealed
      occlusions in the superior mesenteric and right external iliac arteries. The
      resected specimen showed mucosal necrosis of the cecum and circular ulcers at
      Bauhin's valve and at the ascending colon. Microscopically, small mesenteric
      vessels were occluded by organized and recanalized thrombi with preserved
      vascular architecture. The patient has remained free of any further intestinal
      symptoms for 1 year following his discharge from hospital.

PMID- 8292869
TI  - A case of an aortocolic fistula occurring 27 years after aorto-femoral bypass
      surgery, treated successfully by surgical management.
AB  - The secondary aortoenteric fistula (AEF) is a rare but grave complication of
      aortic reconstructive surgery. We report herein a case of an aortocolic fistula
      which occurred 27 years after an aortofemoral bypass. A 69-year-old man was
      admitted to hospital following a sudden episode of melena. He had undergone
      aortofemoral bypass surgery with a prosthetic graft 27 years previously for
      occlusive disease of the right external iliac artery. Colonofiberscopy, CT scan,
      and angiography were performed, and an aortocolic fistula due to an aortic
      anastomotic pseudoaneurysm was diagnosed. The first-stage operation, being
      resection of the previously implanted graft, right hemicolectomy, and aortic
      stump closure were carried out with concomitant axillo-right femoral bypass. A
      femoro-femoral crossover bypass was performed in the second stage and the
      patients recovery followed uneventfully. This case constitutes the longest
      postoperative interval for an AEF recorded in the English literature.

PMID- 8292870
TI  - Improvement of left ventricular function after renal transplantation in a patient
      with uremic cardiomyopathy: report of a case.
AB  - The improvement of heart function in a patient on hemodialysis with dilated
      cardiomyopathy by renal transplantation is herein reported. The patient was a 35
      year-old woman. Hemodialysis had been initiated 3 months before, but she
      experienced difficulty with hemodialysis maintenance and exhibited congestive
      heart failure. The ejection fraction (EF) was decreased to 36.6% in the
      echocardiogram, and an intracardiac biopsy of the right ventricle showed myofiber
      degeneration and interstitial edema upon examination by light microscopy. She
      then underwent renal transplantation, and the postoperative recovery was almost
      uneventful. The cardiothoracic ratio decreased rapidly to around 40% after 1
      month, although her body weight increased. The ejection fraction increased to 50%
      in the echocardiogram. An intracardiac biopsy of the right ventricle revealed
      disoriented myofibers, but myofiber degeneration improved, and no interstitial
      edema was present upon examination by light microscope. The electron microscopy
      showed that the intracellular edema had disappeared and other degenerative
      changes had also improved. The patient was discharged on the 44th postoperative
      day, with a serum creatinine of 1.3 mg/dl.

PMID- 8292871
TI  - Analysis of dystrophin gene deletions in patients from the Mexican population
      with Duchenne/Becker muscular dystrophy.
AB  - Forty unrelated Mexican patients with Duchenne/Becker muscular dystrophy were
      analyzed for intragenic DMD gene deletions, using the multiplex amplification of
      15 deletion-prone exons described by Chamberlain et al. and Beggs et al. The
      percentage of deletions was 52.5%, and the majority of them (86.3%) were located
      at the hot spot deletion region which encompasses exons 44-55. This frequency is
      higher than that found in American and European populations. There were no
      correlations between deletion size, location and clinical severity.

PMID- 8292872
TI  - Production of cytotoxins and enterotoxins by strains of Shigella and Salmonella
      isolated from children with bloody diarrhea.
AB  - The role of toxins in the pathogenesis of bloody diarrhea caused by Shigella and
      Salmonella isolated from children with bloody diarrhea was studied for production
      of toxins active on cells in culture and in rat intestinal loops. Human
      epithelial cells from colon carcinoma (HT-29), Chinese hamster ovary cells (CHO)
      and kidney fibroblast from rhesus monkey (Vero) were used to detect cytotoxins.
      On HT-29 almost 50% of the Shigella and about 20% of the Salmonella strains
      caused rounding of cells; on CHO over 50% of Salmonella and 20% of Shigella
      strains caused elongation of cells, some strains caused also rounding of these
      cells whereas on Vero over 60% of Salmonella and 40% of Shigella strains caused
      rounding of cells. Cytotoxicity on Vero and CHO cells was strongly inhibited with
      cholera toxin antiserum, whereas that on HT-29 was inhibited with C. difficile
      toxin B antiserum. Cytotonic activity on CHO cells and rounding on Vero cells
      seem to be suitable models to detect toxins cross-reacting with cholera toxin.
      Both species, Shigella and Salmonella, produce cytotoxins and enterotoxins which
      could play a role in intestinal disease.

PMID- 8292873
TI  - Effect of plasma freezing temperature, anticoagulant and time of storage on
      factor VIII:C activity in cryoprecipitate.
AB  - The influence of ACD and CPDA-1 anticoagulants, and storage time for 3 and 6
      months on F VIII:C activity were compared in cryoprecipitate obtained at -70
      degrees C, and -30 degrees C plasma freezing temperature. To eliminate variations
      in F VIII:C activity between donor plasma, the cryoprecipitation at -70 degrees C
      and -30 degrees C was made in paired plasma volumes (approximately 100 ml) from
      each blood unit. Employing ACD plasmas (n = 50), there was no significant
      difference in F VIII:C activity between cryoprecipitate prepared at -70 degrees C
      (mean = 31.1 IU/bag) and -30 degrees C (X = 30.5 IU/bag), and the storage did not
      modify F VIII:C activity. In contrast, in cryoprecipitate prepared from CPDA-1
      plasmas (n = 31), the F VIII:C levels obtained at -30 degrees C (mean = 43.8
      IU/bg) were significantly higher than those at -70 degrees C (mean = 37.3
      IU/bag), but a deterioration of F VIII:C activity (about 50%) was observed after
      6 months of cryoprecipitate storage. Therefore, if cryoprecipitate is stored it
      would be more convenient to use ACD instead of CPDA-1 and make cryoprecipitation
      either at -70 degrees C or -30 degrees C.

PMID- 8292874
TI  - Antiestrogen U23,469 induced alterations of catecholamine levels on plasma and
      central nervous system.
AB  - The effect of antiestrogen U23,469 administration in vivo on the concentration of
      dopamine, norepinephrine and epinephrine in the plasma, cerebral cortex and
      hypothalamus in ovariectomized rats was investigated. Rats were treated with
      estradiol benzoate, progesterone and U23,469 in different doses, s.c., daily for
      6 days. Control group was injected with sesame oil. Catecholamines were estimated
      by radioenzymatic assay. Six days of U23,469, estradiol benzoate, progesterone or
      its combination altered the catecholamine levels compared to the control.
      Dopamine decreased in plasma with progesterone and U23,469. In the cerebral
      cortex, progesterone and U23,469 increased significantly and in the hypothalamus
      all the treatments produced a decrease of catecholamines. The levels of NE were
      reduced with estradiol benzoate, progesterone and U23,469; there was no
      significant difference in the norepinephrine levels after different treatments in
      the cerebral cortex, but the NE levels were significantly decreased in the
      hypothalamus. Epinephrine showed differences related to the treatment, as in
      plasma, as in cerebral cortex and hypothalamus. These results suggest that
      antiestrogen treatment compared with the estradiol benzoate or progesterone may
      affect the catecholamine levels of the central nervous system and plasma and
      support the idea that AE could have an indirect effect on the catecholaminergic
      system.

PMID- 8292875
TI  - Antisecretory activity in a lectin fraction of plasma from patients with acute
      diarrhea.
AB  - The present study describes the first attempt to detect antisecretory activity in
      a lectin fraction of plasma from patients with acute diarrhea. The plasma
      antisecretory protein (ASP) was purified by affinity chromatography in agarose,
      and its antisecretory activity tested in rats subjected to intestinal challenge
      with cholera toxin. During the first 24 h of the diarrheal episode, antisecretory
      activity in patients (median 0, range 0-25%) was lower than that seen in the
      asymptomatic group (median 10, range 0-30%); 3 days later, when diarrhea ceased
      in most of the patients, the ASP activity increased significantly (median 30,
      range 0-75%). However, 5 days later the activity decreased again (median 0, range
      0-55%). No differences in ASP levels were found between cases associated with an
      enteropathogen and those where no pathogen was identified. These findings reveal
      an inverse relationship between the increase in ASP and the patient's intestinal
      secretion; suggesting that ASP plays a role in the compensatory mechanisms that
      occur in diarrhea in humans.

PMID- 8292876
TI  - Autonomic dysfunction in chronic liver disease.
AB  - Chronic liver disease is accompanied by a number of circulatory changes including
      impairment of cardiovascular autonomic reflexes. This occurs irrespective of the
      aetiology of liver disease, increases in prevalence and severity with worsening
      hepatic function, and is related at least in part to an autonomic neuropathy.
      Parasympathetic abnormalities predominate and, although largely subclinical, they
      may play a role in the altered fluid homeostasis and neurohumoral disturbances
      associated with cirrhosis. On prospective follow up, the presence of autonomic
      impairment was associated with a five-fold increased mortality, largely from
      sepsis and variceal haemorrhage. Defective responses to such stressful events as
      a result of an afferent defect could possibly explain these findings. Further
      studies are required to evaluate the natural history of this complication, and
      determine if it is reversible with improvement in hepatic function or after liver
      transplantation.

PMID- 8292877
TI  - Thermoregulatory response to passive body heating in borderline hypertension.
AB  - Sweating and vasodilatation in the cutaneous circulation were investigated during
      passive body heating in eight borderline hypertensive subjects and in eight
      normotensive controls, matched for age, sex and body mass. Blood flow through the
      finger and forearm was examined in relation to changes in oral temperature; blood
      pressure, heart rate and sweating in the forehead and forearm were also measured.
      Systolic blood pressure decreased in borderline hypertensive subjects during the
      early stages of heating and then returned to baseline, but increased in
      normotensives. Increases in skin blood flow and decreases in cutaneous vascular
      resistance were similar in both groups. Thus, cutaneous vasodilatation during
      moderate body heating did not differ between normotensive subjects and subjects
      with mildly elevated blood pressure. These findings do not rule out attenuation
      of cutaneous vasodilatation in mildly hypertensive subjects during more intense
      heating.

PMID- 8292878
TI  - Unilateral loss of facial flushing and sweating with contralateral anhidrosis:
      harlequin syndrome or Adie's syndrome?
AB  - A 45-year-old woman presented with a 10 year history of asymmetrical facial
      flushing and sweating after exertion or in hot weather. During these episodes the
      right side of her face remained dry and white, while the left side normally
      flushed. Sweating was impaired on the left side in the limbs and trunk. She also
      had areflexia in the lower limbs and slow pupillary reactions to light and
      darkness, as seen in Adie's syndrome. The topography of the sweating disorder
      suggested that the lesion involved the sympathetic pathways at the level of
      spinal cord. The relationship with the harlequin syndrome and related disorders
      is discussed.

PMID- 8292879
TI  - Clinical, laboratory and prognostic features of congenital large intestinal motor
      dysfunction (pseudo-Hirschsprung's disease).
AB  - One hundred and forty-eight cases of congenital large intestinal motor
      dysfunction (pseudo-Hirschsprung's disease) were reported by members of the
      Japanese Society of Pediatric Surgeons during the past 20 years. The disorder was
      defined as a congenital, non-mechanical obstruction of the intestine with the
      presence of intramural ganglia in the terminal rectum. Intramural ganglia were
      abnormal in 77 cases, normal in 42, and could not be determined in 29. Of those
      with abnormal intramural ganglia, 54 had immature ganglia or hypoganglionosis
      (oligoganglionosis), 15 had neuronal intestinal dysplasia, and eight had a
      segmental anomaly. Of those with a normal myenteric plexus, 22 had chronic and
      twelve had suspected idiopathic intestinal pseudo-obstruction syndrome; eight had
      megacystis-microcolon-intestinal hypoperistalsis syndrome. While cases with both
      hypoganglionosis and normal intramural ganglia had normal acetylcholine esterase
      activity, a significantly greater number of patients with hypoganglionosis lacked
      normal rectoanal reflexes. Patients with hypoganglionosis, chronic idiopathic
      intestinal pseudo-obstruction syndrome, and megalocystis-microcolon-intestinal
      hypoperistalsis syndrome had poor prognoses with an overall mortality of 36.9%.
      These findings indicate that congenital large intestinal motor dysfunction
      remains a serious disease of childhood.

PMID- 8292880
TI  - Early nocturnal blood pressure changes in diabetic autonomic neuropathy assessed
      by Fourier series.
AB  - The 24 h periodic pattern of blood pressure was studied in 44 patients with
      diabetes mellitus (14 type 1, 30 type 2; mean duration of disease 6.5 +/- 1.8
      years) in good metabolic control but with abnormal cardiovascular reflex
      responses; of these 21 were normotensive and 23 hypertensive. All had abnormal
      responses to at least two out of four tests: deep breathing, lying to standing,
      Valsalva manoeuvre and postural hypotension. Two sex- and age-matched groups,
      consisting of 20 normotensive and 20 hypertensive diabetic patients without
      dysautonomia, were studied as controls. Each patient underwent ambulatory blood
      pressure monitoring for at least 24 h, using an auscultatory automatic device.
      Data were analysed using the sum of three periodic functions (Fourier partial
      sum). In the diabetic normotensive groups, the absolute blood pressure fell to
      its night-time minimum more rapidly, and increased to its morning maximum more
      slowly, in those with abnormal cardiovascular reflexes than in the controls
      (nightly blood pressure decrease -5.8/-4.7 vs. -3.8/-4.0 mmHg/h; increase 4.7/3.6
      vs. 5.9/6.1 mmHg/h). The same behaviour was found in both hypertensive groups but
      the amplitude of the differences was more marked (blood pressure nocturnal
      decrease -7.7/-7.1 vs. -4.3/-3.9 mmHg/h; increase 3.2/2.1 vs. 5.8/4.3 mmHg/h).
      This analysis of 24 h ambulatory blood pressure data may be of value in diagnosis
      and evaluation of autonomic deficits.

PMID- 8292881
TI  - 24 hour ambulatory blood pressure variability and cardiac parasympathetic
      function 2 and 6 weeks after acute myocardial infarction.
AB  - The aim of the study was to assess non-invasively circadian blood pressure rhythm
      as well as the influence of parasympathetic function 2 and 6 weeks after acute
      myocardial infarction treated with beta-blocking agents. Twenty-four patients
      with uncomplicated first myocardial infarction, and aged less than 60 years,
      underwent ambulatory blood pressure recordings every 15 min during the day (0900
      2100 h) and every 30 min during the night (2100-0900 h), 2 and 6 weeks after
      infarction. The deep breathing test (6 breaths/min) was performed on each
      occasion. Normal circadian blood pressure rhythm was maintained with a nocturnal
      decline of 10 to 15%. Both for systolic and diastolic blood pressure a moderate
      increase was obtained after 6 weeks (107.8 +/- 9.2 mmHg vs. 111.8 +/- 10.3 mmHg;
      NS and 64.9 +/- 4.5 mmHg vs. 68.8 +/- 6.5 mmHg; p < 0.05). The respective blood
      pressure variations were significantly higher at that time (10.0 +/- 2.4 mmHg vs.
      13.6 +/- 4.2 mmHg; p < 0.001 and 7.9 +/- 1.7 mmHg vs. 11.7 +/- 3.5 mmHg, p <
      0.001). There was a close correlation (r = 0.60, p < 0.005) between 24-h
      diastolic blood pressure variability and the results of the parasympathetic
      function test (deep breathing) 2 weeks after infarction. We conclude that the
      circadian blood pressure rhythm persists after acute myocardial infarction. The
      correlation between blood pressure variability and parasympathetic function early
      after infarction suggests a role for vagal control in post-infarction blood
      pressure variability.

PMID- 8292882
TI  - Spectral analysis of heart rate in vasovagal syncope: the autonomic nervous
      system in vasovagal syncope.
AB  - Spectral analysis of heart rate fluctuations was used to investigate the role of
      the autonomic nervous system in the pathogenesis of vasovagal syncope. Nine
      adolescents with a history of at least three episodes of vasovagal syncope and
      nine age-matched healthy controls were studied. All subjects were tested in
      supine position and at a 60 degrees inclination for 60 min or less if syncope
      developed. Blood pressure and heart rate were measured, while the ECG and
      respiration traces were recorded on magnetic tape for later spectral analysis.
      Baseline heart rate was lower in control subjects than in patients, increased
      with tilt in both groups, and remained lower in the control subjects throughout
      the experiment. Baseline systolic and diastolic blood pressure was similar in
      both groups. Diastolic blood pressure initially increased with tilt in all
      subjects and decreased significantly thereafter in patients. Pulse pressure was
      lower in patients throughout the experiment. The heart rate power spectra
      displayed a higher baseline level of low frequency fluctuations in the control
      group. The high frequency fluctuations component was similar in all subjects. The
      results of the test, regarding haemodynamic parameters and autonomic control of
      the heart rate, as expressed by low and high frequency fluctuations, are
      consistent with a reduced sympathetic reserve in the individuals with previous
      episodes of syncope.

PMID- 8292883
TI  - The effect of recombinant human erythropoietin on cardiovascular responses to
      postural stress in dialysis patients.
AB  - The normal response to 45 degrees head-up tilt (decreased stroke volume and
      cardiac output and increased heart rate and peripheral resistance) is not seen in
      the majority of haemodialysis patients. This is due to both an abnormal
      baroreceptor reflex and increased venous tone which may be explained by a number
      of factors including hypoxia, acidosis and sodium retention. We have studied this
      response by impedance cardiography in eight chronic haemodialysis patients, both
      before and after 3 months of treatment with human recombinant erythropoietin.
      Before treatment the cardiovascular parameters were abnormal both at rest and on
      tilting in each patient. The change in each measurement following tilting was:
      stroke volume, 0.5 +/- 6%; cardiac output, 6 +/- 5%; peripheral resistance, -8 +/
      4%; and heart rate, 10 +/- 4%. After 3 months of erythropoietin (150 U/kg/week
      intravenously) the mean haematocrit had risen from 19.5 +/- 3% to 32.9 +/- 4% and
      all patients felt physically fitter. Impedance showed no change in the supine
      indices but after tilting there was a dramatic fall in stroke volume (-26 +/- 7%)
      and cardiac output (-17 +/- 7%) and an increase in heart rate (15 +/- 4%) and
      peripheral resistance (28 +/- 10%) each moving towards the normal response. These
      results indicate that human recombinant erythropoietin normalizes the response to
      postural stress in these patients and suggest that anaemia is the principal cause
      of the abnormal venoconstriction seen in haemodialysis patients. The mechanisms
      involved warrant further investigation.

PMID- 8292885
TI  - Olfactory dysfunction in the Shy-Drager syndrome.
AB  - The aetiology of the Shy-Drager syndrome (multiple system atrophy) is unknown. We
      reported previously a preliminary association between environmental-occupational
      risk factors and Shy-Drager syndrome. To further investigate this relationship,
      we evaluated olfactory function in eight patients in different stages of disease.
      When the eight patients' olfactory function was compared with 203 age- and sex
      matched controls using a self-administered olfactory test, seven scored below the
      39th percentile of this population. Five of the eight patients had total anosmia
      or microsmia. Additional studies will be required to elucidate the significance
      of this abnormal clinical observation.

PMID- 8292884
TI  - Brain natriuretic peptide and fluid volume homeostasis--studies during
      cardiopulmonary bypass surgery.
AB  - Brain natriuretic peptide (BNP) is a recently identified cardiac ventricular
      hormone with diuretic, natriuretic and vasorelaxant properties. The aim of our
      study was to examine whether serial changes in endogenous levels of BNP were
      associated with fluid volume homeostasis following cardiopulmonary bypass. We
      studied nine patients undergoing elective cardiac surgery for the repair of
      cardiac abnormalities requiring cardiopulmonary bypass. Urinary levels of cyclic
      guanosine monophosphate (cGMP), sodium, urine output, fluid balance, and plasma
      levels of BNP, aldosterone, plasma renin activity (PRA) and central venous
      pressure (CVP) were measured before, during and after cardiopulmonary bypass.
      Basal pre-operative plasma BNP levels were highly elevated in all nine patients
      with cardiac abnormalities. During bypass, pre-operative levels of BNP, urinary
      cGMP and plasma aldosterone decreased significantly (p < 0.05), whereas pre
      operative levels of urinary sodium and PRA were slightly reduced. During recovery
      following bypass levels of urinary cGMP, sodium, PRA and aldosterone returned to
      basal pre-operative values, whereas post-operative levels of plasma BNP were
      found to be three-fold below basal pre-operative levels. CVP (4.3 +/- 0.2 mmHg)
      during the onset of bypass increased significantly (p < 0.05) at the end of
      bypass (9 +/- 0.3 mmHg) followed by a modest increase post-operatively (10 +/-
      0.4 mmHg). After operation only BNP had a significant correlation with urine
      output (r = -0.82, p < 0.02) and net fluid balance (r = -0.84, p < 0.01), whereas
      urinary cGMP, PRA and aldosterone all exhibited a non-significant correlation
      with urine output.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292886
TI  - Surgical treatment of ocular melanoma.
AB  - Malignant melanomas may arise in the uveal tract, the conjunctiva, the skin of
      the eyelid, or the orbit. Risk factors so far identified include pre-existing
      choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for
      conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and
      orbital lesions. The atypical mole syndrome (AMS) is associated with uveal and
      conjunctival melanomas, especially when the ocular lesions are multiple or
      familial. AMS patients should be screened for ocular melanomas. Conjunctival
      melanomas are managed by excision with or without adjunctive beta-irradiation.
      Circumscribed tumours have a better prognosis than diffuse and multifocal lesions
      arising in acquired melanosis and attempts should be made to limit the progress
      of the latter variant of the disease by treating PAM with cryotherapy. The most
      significant prognostic factor in uveal melanoma is the size of the tumour at
      presentation. Early dissemination is the rule and every effort should be made to
      distinguish a melanoma from a naevus as soon as possible. Small and medium-sized
      melanomas respond well to focal treatments chosen according to the size and
      location of the tumour. The techniques employed include photocoagulation,
      radioactive plaque therapy, proton beam radiotherapy and surgical resection.

PMID- 8292887
TI  - Expression of CALLA/CD10 on human melanoma cells.
AB  - The reactivity spectrum of an anti-CALLA/CD10 monoclonal antibody for cutaneous
      melanoma was analysed by immunohistochemistry in a series of lesions of different
      Breslow thickness. Similar proportions of small primary tumours, advanced primary
      tumours and metastatic lesions were found to express CALLA/CD10 (31-47%). However
      the proportion of stained cells within a given lesion increased with tumour
      progression. Up to 23% of the advanced primary lesions (> 3.0 mm) showed 26-50%
      cells stained with the anti-CALLA/CD10 antibody and up to 14% of the metastatic
      lesions showed 76-100% stained cells. The expression of CALLA/CD10 was further
      analysed in 15 ocular melanoma lesions of different histiotype. All five spindle
      type lesions, three of six epitheloid and two of five mixed type lesions stained
      positively with the anti-CALLA/CD10 antibody. The percentage of stained cells
      within a given lesion varied from 30% to 100%. A total of 63% of the ocular
      melanomas and 38% of the cutaneous melanomas tested expressed CALLA/CD10.
      Experiments with cultured melanoma cell lines showed that the surface expression
      of CALLA/CD10 can be modulated in vitro by treatment with interleukin 2 (IL-2)
      and an adenosine 3',5'-cyclic monophosphate (analogue).

PMID- 8292888
TI  - S-100 protein remains a practical marker for melanocytic and other tumours.
AB  - S-100 protein, extracted from bovine brain, is the first described of the modern
      generation of marker molecules for melanocytic tumours. Despite the observation
      that many different types of cells express S-100 protein, detection of the
      molecule in tumour cells in appropriate clinical and pathological circumstances
      is a widely used and effective adjunct to the determination that a tumour is
      melanocytic. Antibodies to S-100 protein are best deployed as part of a package
      that includes antibodies to other melanoma-associated epitopes (HMB-45, NKI
      C3/Beteb), cytokeratins and common leukocyte antigen. Antibodies to S-100 protein
      may also increase the accuracy of melanoma staging and permit detection of small
      numbers of metastatic tumour cells that are not detectable by conventional
      histology. Future applications will probably include the wider use of antibodies
      to the S-100 protein monomers (alpha and beta) and the detection and
      quantification of S-100 protein in body fluids and tissues.

PMID- 8292890
TI  - The progression associated antigen MUC18: a unique member of the immunoglobulin
      supergene family.
AB  - The cell surface glycoprotein MUC18 was originally identified as a progression
      associated antigen in melanoma. MUC18 is expressed most strongly on metastatic
      lesions and advanced primary tumours and is only rarely detected in benign
      lesions. cDNA cloning revealed MUC18 to be a novel member of the immunoglobulin
      superfamily with sequence similarity to a number of cell adhesion molecules.
      Cloning of both the human and mouse MUC18 genes indicate that their predicted
      protein structures are very similar with an overall amino acid identity of 75%.
      Like its human counterpart, murine MUC18 is also expressed by transformed
      melanocytes. Analysis of the promoter region of the human gene has provided
      evidence for regulatory elements found in smooth muscle specific genes and in
      both human and mouse: this is the normal site of MUC18 expression. The presence
      of putative binding sites for the transcriptional factors AP-1, AP-2 and CREB,
      suggest that MUC18 gene expression can also be modulated by external factors.

PMID- 8292889
TI  - Characterization of melanosome-associated proteins by establishment of monoclonal
      antibodies and immunoscreening of a melanoma cDNA library through an anti
      melanosome antibody.
AB  - Monoclonal antibodies against melanosomal components (human melanosome specific
      antigens; HMSAs) have been developed in our laboratory. HMSA-1-4 recognizes
      structural matrix proteins of melanosomes. HMSA-5 is identical to TRP-1,
      equivalent to the b (brown) locus of murine melanocytes and expressed in early
      stages of melanosomal maturation. HMSA-6 is a protein associated with melanosomes
      but its role is still unclarified, and HMSA-7 is identical to the lysosomal
      protein CD63. We have also recently identified p90 calnexin-like, Ca(2+)-binding
      protein p97 melanotransferrin, and p64 beta-D-galactosidase-like protein
      associated with melanosomes through immunological screening of our melanocytes
      (melanoma cells) cDNA library. Approximately 150 genes and 60 loci are known to
      influence eye, skin and hair colour in mammals. Tyrosinase is a rate-limiting
      enzyme responsible for melanin synthesis. In addition, tyrosine-related proteins
      (TRPs) and their genes have been identified and cloned. Tyrosinase and TRPS
      (e.g., TRP-1; b-locus protein identical to HMSA-5 and TRP-2; dopachrome
      tautomerase) are synthesized according to underlying genetic programmes, and are
      up- and/or down-regulated to create various forms of abnormal melanin
      pigmentation. We herein propose the importance of investigating the role of non
      tyrosinase related proteins such as those which we have recently identified.

PMID- 8292891
TI  - The Ca2+ channel blocker verapamil enhances melanogenesis without altering
      metastatic potential in the B16 murine melanoma.
AB  - The relationship between the processes of melanogenesis and metastasis were
      investigated using metastatic variants of the B16 murine melanoma. alpha
      Melanocyte stimulating hormone (MSH) enhanced lung colonization by the low
      metastasis variant F1 as well as inducing melanogenesis. The Ca2+ channel blocker
      verapamil had no effect on lung colonization by the F1 and ML8 variants but
      markedly enhanced melanogenesis in both these cell lines. We previously showed
      that the expression of the dominant metastasis associated gene mts1 was up
      regulated by MSH but down-regulated by verapamil. These findings may demonstrate
      that the processes of melanogenesis and metastasis can be uncoupled at both
      genetic and phenotypic levels, and that the mechanisms involved in the regulation
      of metastatic behaviour and melanogenesis are different.

PMID- 8292892
TI  - Repair of potentially lethal damage: its inhibition by hyperthermia in two human
      melanoma cell lines with different radio- and heat sensitivities.
AB  - The effect of hyperthermia on the inhibition of potentially lethal radiation
      damage repair (PLDR) was measured in two human melanoma cell lines of differing
      radiosensitivities. The HT144 cell line is radiation sensitive and has an
      exponential survival curve, while the SK-MEL-3 line is radiation resistant and
      has a shouldered survival curve. Both cell lines demonstrated a similar level of
      PLDR at isosurvival level radiation doses of 2.0 and 10 Gy for the HT144 and SK
      MEL-3 lines, respectively. Hyperthermia (40-45 degrees C) could inhibit PLDR in
      both cell lines. This inhibition was greater in HT144 than in SK-MEL-3 at low
      temperatures (40 degrees C) and was reversed at higher temperatures (45 degrees
      C). There was also a sequence dependence of PLDR inhibition which showed a
      greater inhibition for heat before irradiation at 40 degrees C but the reverse
      for temperatures of 41 degrees, 43 degrees and 45 degrees C. These data show that
      hyperthermia can be an effective inhibitor of PLDR in both radiosensitive and
      resistant cell lines and that the degree of inhibition is not related to
      radiosensitivity.

PMID- 8292893
TI  - Influence of an autocrine diffusible resistance factor on cell survival after
      exposure to therapeutic agents.
AB  - A subclone of Cloudman mouse melanoma cells (S91/I3) produces a resistance factor
      (RF) that increases the survival of a different but related subclone, S91/Amel,
      after exposure to either ultraviolet C (UVC) radiation or to mitomycin C (MMC).
      The presence of RF was deduced from experiments in which heavily irradiated
      S91/I3 cells were plated with the target S91/Amel cells. The effect of RF was
      also present in cell-free conditioned tissue culture medium (CM) from S91/I3
      cultures. These results extend previous findings that both subclones produce an
      autocrine resistance factor (RF) that alters the radiation response of target
      S91/Amel cells making them less sensitive to death by low linear energy transfer
      (LET) ionizing radiation. S91/I3 cells are radioresistant relative to S91/Amel
      and produce the RF more effectively than S91/Amel. S91/I3 cells do not respond to
      the RF, being themselves, presumably, maximally stimulated. The significant
      findings are (1) the RF is effective at decreasing the killing of the target
      cells using cytotoxic agents that operate by different mechanisms; (2) The
      relative sensitivities of S91/Amel and S91/I3 to the toxic agents is not a factor
      in the responses of these cells to the RF: S91/Amel survivals are increased by
      the RF, those of S91/I3 are not; (3) the RF is elaborated by the melanoma cells
      whether or not they have been irradiated; it is, apparently, a normal cell
      product; (4) the RF is effective when added after the cytotoxic insult; its
      presence is not required during irradiation or drug treatment. The RF appears to
      act by novel mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292894
TI  - Diverse activity of sc-RIP saporin 6 on primary and metastatic melanoma cells in
      vitro.
AB  - The inhibitory effect of saporin 6, a single-chain ribosome-inactivating protein
      (sc-RIP) purified from the seeds of Saponaria officinalis, on the proliferation
      of human primary (MeWo, WM 164, SK MEL 28, MEM), cloned (MEM A9, A12, A13) and
      metastatic (M14) melanoma cells has been tested by protein synthesis and colony
      formation assays in vitro. Results indicate a marked difference in the
      sensitivity of primary and metastatic cells to the action of saporin 6, the
      latter being significantly more affected, both in treated and in pretreated
      cultures, with a high and specific response evident after 24 h of treatment and
      progressively increasing up to 72 h of culture with the drug (IC50 = 0.82
      microgram/ml). This effect, which was dose-dependent in exponentially growing
      cells, was partially reversed upon removal of the inhibitor from the culture
      medium. No inhibitory effect was evident in the MeWo primary cells at the highest
      saporin 6 concentration used: the p170 glycoprotein-mediated mechanism is not
      involved in such a resistance pathway.

PMID- 8292895
TI  - Penetration and binding of L- and D-carboranylalanine in human melanoma
      spheroids.
AB  - The principle of boron neutron capture therapy (BNCT) is that a cell-specific 10B
      containing substance binds to tumour cells and irradiation with thermal neutrons
      is performed when the 10B concentration, in relation to the levels in critical
      normal tissues, is at a maximum. Some boron compounds have recently been proposed
      for BNCT of malignant melanomas; the synthesized L- and D- forms of
      carboranylalanine and the previously tested compound L-p-boronophenylalanine are
      candidates. Human melanoma, IGR1, spheroids were used as models of melanoma
      nodules in this study. The spheroids developed central necrosis when they were
      about 480 microns in diameter and the volume doubling time was 2.6 +/- 0.3 days.
      The tritiated thymidine labelling index decreased rapidly as a function of
      distance from the periphery and was, at a depth of 175 microns, close to zero.
      The penetration patterns showed, for L- and D-carboranylalanine and L-p
      boronophenylalanine, a homogeneous distribution of 10B throughout the spheroids
      by 5 min. L-Carboranylalanine gave a more or less even binding of 10B throughout
      the spheroids and large amounts were present also in the central necrotic
      regions. D-Carboranylalanine also gave a homogeneous 10B binding in the viable
      cell layers while the binding in the central necrotic area was lower and a
      similar, but somewhat lower, binding was found for L-p-boronophenylalanine. Thus,
      there were no penetration barriers for the boron compounds and binding of 10B was
      found also in the deeper regions of the viable cell layers. The results showed
      that the new carboranylalanine compounds are of interest for further analysis,
      including toxicological and pharmacological studies in vivo.

PMID- 8292896
TI  - Changes in plasma 5-S-cysteinyldopa concentration in B16 melanoma-bearing mice
      treated with interferon-beta or dacarbazine.
AB  - We have previously shown that the urinary excretion of 5-S-cysteinyldopa (5-S-CD)
      reflects well the progression of B16 mouse melanoma. We examined the usefulness
      of plasma concentration of 5-S-CD in following the progression of melanoma and
      evaluating the efficacy of immuno- and chemotherapeutic agents in the B16 mouse
      model. Murine interferon-beta (MuINF-beta; 3 x 10(5) U) or dacarbazine (DTIC; 50
      mg/kg) was administered once a day for 10 or 5 consecutive days starting 8 days
      after subcutaneous inoculation of B16 melanoma cells in C57BL/6 mice. Blood
      samples were collected from the tail vein and tumour volumes were measured every
      other day until day 24. Levels of 5-S-CD in plasma were determined by high
      performance liquid chromatography. Tumours became palpable on day 6-8 and grew
      exponentially thereafter in the control mice. Tumours in INF-beta-treated mice
      also grew exponentially, although at a reduced rate. However, the growth of
      tumours in the DTIC-treated mice was almost suppressed between days 12 and 18.
      Mean values of tumour volume on day 16 were 1.45, 1.05, and 0.83 cm3 in the
      control, INF-beta-treated, and DTIC-treated groups, respectively. The plasma
      concentration of 5-S-CD began to increase on day 8, at much slower rates in the
      experimental groups than those in the control group. Mean values of plasma 5-S-CD
      on day 16 were 14.3, 5.9, and 5.6 nmol/l in the control, INF-beta-treated, and
      DTIC-treated groups; 5-S-CD level on day -2 was 1.8 nmol/l.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8292897
TI  - European Organization for Research and Treatment of Cancer (EORTC)-Melanoma
      Cooperative Group (MCG) meeting. San Miniato, 23-24 April 1993.

PMID- 8292898
TI  - HIV and complement: role of the complement system in HIV infection.
AB  - HIV, in contrast to animal retroviruses, is not lysed by human serum but
      nevertheless the virus as well as virus-infected cells activate the complement
      system efficiently. HIV activates the classical pathway by binding C1q to the
      transmembrane protein gp41. On the surface of HIV-infected cells, both the
      alternative and the classical pathway are activated. Complement-treated HIV has
      an enhanced ability to infect cells carrying receptors for C3 fragments. By this
      mechanism complement can target the virus to certain cells, e.g. follicular
      dendritic cells. HIV-infected complement-coated cells can interact with
      complement receptor carrying cells and thereby spread the infection or cause the
      destruction of the infected cells. Due to direct or indirect effects of HIV the
      complement system is in an activated state and the cellular expression of
      complement receptors as well as regulatory molecules is modified in the blood of
      HIV-infected patients.

PMID- 8292899
TI  - Infectious AIDS--stretching the germ theory beyond its limits.
AB  - The hypothesis that human immunodeficiency virus (HIV) causes AIDS was advanced
      in 1984, based only on circumstantial evidence. To this date, the primary
      evidence are correlations between the presence of antibody against HIV and AIDS.
      But these correlations are biased by proponents of the HIV hypothesis in favour
      of HIV. They ignore HIV-free AIDS and they base correlations on selected studies
      because there are no national HIV-AIDS statistics. The HIV-AIDS hypothesis has
      made the following predictions: (1) AIDS would 'explode' from the original risk
      groups into the general population via sexual transmission of HIV. (2) Health
      care workers would contract AIDS from their patients, scientists from propagating
      HIV, and prostitutes from their clients. (3) The 150 chimpanzees that have been
      experimentally inoculated with HIV, and the 15,000 American hemophiliacs who have
      been iatrogenically inoculated before 1984, would develop AIDS. (4) Antiviral
      immunity and vaccines would protect against AIDS. (5) HIV would cause AIDS by
      killing T-cells. (6) AIDS would occur only in people infected by HIV. But none of
      these predictions proved to be correct. Recent studies show that HIV is a
      passenger virus instead of the cause of AIDS: (1) AIDS occurs at unpredictable
      intervals after infection; (2) HIV may be active, passive, or totally absent from
      otherwise identical AIDS cases. Indeed, AIDS does not meet one of the classical
      criteria of infectious disease: (1) Equal distribution between the sexes; (2)
      disease following infection within days or weeks, the time microbes take to
      become either immunogenic or pathogenic or both; (3) the presence of a common
      active microbe. Therefore it is proposed that American and European AIDS is
      caused by the long-term consumption of recreational drugs and the anti-HIV drug
      AZT. This hypothesis is testable and provides a rational basis for AIDS control.

PMID- 8292900
TI  - Duesberg on AIDS--stretching our benevolence beyond its limits.

PMID- 8292901
TI  - Lymphocyte Proteinpaedia stage two: T-cell polypeptides from a partitioned cDNA
      library revealed by the dual decay method.
AB  - A complex population of gene products was analyzed by combining the great
      resolving power of two-dimensional (2D) protein electrophoresis with a detailed
      dissection of individual protein species afforded by cDNA cloning. A cDNA library
      from BW5147 was partitioned by random sampling into sectors (of a complexity of
      500 phase plaques/sector). From each of the unique sets of cDNA clones present in
      the sector, 2D gels were prepared. Patterns of spots were analyzed using the
      Kepler software system, and the compiled data both from the sectors and from the
      natural lymphocyte populations have been established to serve as a guide for gene
      retrieval. Use of the dual decay method, which compares two exposures of a 2D gel
      co-electrophoretic pattern, obtained from samples with (35S)-polypeptides mixed
      with (3H)-polypeptides, is described and scrutinized. It was determined that of
      268 spots (three sectors combined), 118 spots were shared with the natural
      lymphocyte population, the remaining 150 spots occur only in the sectors (and not
      detected in the cell population). All cDNA populations are available for
      retrieval. Information obtained throughout the work was entered into the
      database.

PMID- 8292902
TI  - Human leukocytes contain angiotensin I, angiotensin II and angiotensin
      metabolites.
AB  - Angiotensin I (ANG I) and angiotensin II (ANG II) were measured
      radioimmunologically in human leukocytes extracted with a mixture of acetone, 1N
      HCl and water (40:1:10 vol). The analytical recoveries of 125I-ANG I and 125I-ANG
      II, which were added prior to extraction, were 92.00 +/- 3.10 and 99.19 +/- 0.91%
      (mean +/- SEM; n = 12). The concentration of ANG I- and ANG II-like material in
      leukocytes from healthy volunteers was 32.04 +/- 3.64 and 13.05 +/- 1.26 fmol/mg
      protein (n = 24). The immunoreactive material could be characterized on HPLC as
      Ile5-ANG I, Ile5-ANG II and angiotensin metabolites such as Ile4-ANG III, Ile3
      ANG II hexapeptide, Ile2-ANG II pentapeptide and Ile1-ANG II tetrapeptide. From
      the ANG I-immunoreactive material determined in the extracts, 26% could be
      characterized on HPLC as Ile5-ANG I. The ANG II-immunoreactive material present
      in the extracts could be separated on HPLC into 44% Ile5-ANG II, 14% Ile4-ANG
      III, 7% Ile3-ANG II hexapeptide, 4% Ile2-ANG II pentapeptide and 8% Ile1-ANG II
      tetrapeptide. Patients with a history of anaphylactic reactions to bee or wasp
      venom showed significantly reduced ANG II concentrations in their leukocytes as
      compared to controls (6.76 +/- 0.76 fmol ANG II/mg protein, n = 22, vs. 13.05 +/-
      1.26 fmol ANG II/mg protein, n = 24; p < 0.05). A significant correlation between
      the severity of clinical symptoms and the ANG II levels was found for grade I and
      II reactions (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292903
TI  - Efficacy of the placental barrier for immunoglobulins: correlations between
      maternal, paternal and fetal immunoglobulin levels.
AB  - The relationship of immunoglobulin levels in fetal and parental blood for those
      classes showing a high degree of placental impermeability was investigated in 430
      mothers, their newborn infants (cord blood) and their husbands. Levels of IgA,
      IgD and IgM in maternal serum were unrelated to the sex of the offspring. IgE
      levels were significantly higher in mothers of male infants than in mothers of
      female infants (53 versus 40 IU/ml, p < 0.02). Significant correlations between
      maternal-fetal (r = 0.37; p < 0.01), paternal-fetal (r = 0.12; p < 0.02) and
      maternal-paternal IgE levels were found (r = 0.17; p < 0.02). For the levels of
      other immunoglobulins studied, the maternal-fetal correlations were not
      significant. The results support the effectiveness of the placental barrier for
      IgA, IgD, IgE and IgM. The significant correlation between IgE levels in mothers
      newborns, fathers-newborns and mothers-fathers may be explained by the influence
      of the home milieu on the entire family, including the fetus.

PMID- 8292904
TI  - Role of lymphatic drainage on the development of Calmette-Guerin bacillus-induced
      granulomas in the hamster.
AB  - The influence of lymphatic drainage on Calmette-Guerin bacillus (BCG)-induced
      granulomas was investigated by comparing the time course of granuloma formation
      in two sites: the hamster footpad and the check pouch, an area deprived of
      lymphatic vessels. Typical epithelioid granulomas developed in both sites.
      Whereas in the footpad the size of granulomas increased and the volume of the
      lesion persisted, in the pouch the lesion decreased in volume. The inoculation of
      BCG into the footpad of animal with granulomas in the pouch, reactivated the
      pouch lesions. T lymphocytes were detected by an immunocytochemical technique at
      the edge of these lesions. Inoculation of the bacteria into the pouch induces
      suppressive mechanisms which hold down the volume of the lesions induced in the
      footpad. The cutaneous purified protein derivative (PPD) test, positive in
      animals inoculated in the footpad, was always negative in animals with granulomas
      in the pouch. The number of bacteria per microscopic field in pouch granulomas
      increased from 10 to 1,000 after PPD injection. Evidence that PPD has a direct
      effect on pouch granuloma cells is given.

PMID- 8292905
TI  - Activation of human blood lymphocytes by house dust mite protein and
      Mycobacterium tuberculosis purified protein derivative: effects of interferon
      gamma, interleukin-4, dexamethasone and cyclosporin A.
AB  - Peripheral blood mononuclear cells (PBMC) from nonatopic donors sensitive to
      Mycobacterium tuberculosis purified protein derivative (PPD) and from atopic
      donors sensitive to PPD and house dust mite antigen (HDM), were stimulated in
      vitro to proliferate in response to exogenous IL-2. In the presence of exogenous
      IFN-gamma, the response of cells from atopic donors to PPD was either unaffected
      or slightly enhanced, whereas the response to HDM was inhibited in a dose
      dependent manner. The response of cells from nonatopic donors to PPD remained
      unchanged or was only slightly inhibited and this was not dose-dependent.
      Exogenous IL-4 did not reverse the inhibitory effects of IFN-gamma and a
      neutralizing antibody to IL-4 did not inhibit the proliferative response of cells
      to HDM and IL-2. Dexamethasone inhibited the IL-2-mediated response of cells from
      atopic donors stimulated with HDM, whereas the IL-2-mediated response of cells
      induced by PPD was either unchanged or stimulated by dexamethasone. Cyclosporin A
      inhibited the response of cells to both HDM and PPD. These results suggest that
      IFN-gamma can exert a selective effect on the response of T lymphocytes to
      different antigens and that it is possible to identify compounds able to regulate
      this activity.

PMID- 8292906
TI  - Altered immune response to proteins fed after neonatal exposure of piglets to the
      antigen.
AB  - The weaning of piglets onto soya proteins at 3 weeks old normally results in an
      active response to the fed protein, as determined by the appearance of serum IgG
      antisoya antibody. This system thus allows the effects of manipulation on the
      response to a fed protein to be studied. In animals previously given 1 g of soya
      protein at birth, the magnitude of the antibody response to soya fed at 3 weeks
      was decreased, although similar amounts of the fed protein could be detected in
      serum. In addition, the relative affinity of the dominant interaction between
      antigen and antibody was reduced in these piglets by almost an order of
      magnitude. By comparison, the ability of piglets given soya at birth to respond
      to injected soya was not significantly reduced. These results indicate that the
      regulation of responses to fed and systemic antigens is largely separate. Very
      early oral exposure to antigen may affect the ability of neonatal animals to
      mount immune responses to, specifically, fed proteins while leaving the response
      to systemic antigen largely intact.

PMID- 8292907
TI  - Placebo-controlled immunotherapy with Cocos nucifera pollen extract.
AB  - The effectiveness of Cocos nucifera pollen extract immunotherapy (CPE-IT) was
      studied in 96 patients allergic to C. nucifera pollen. A placebo-controlled study
      was performed at random for a period of 6-12 months. The clinical status of the
      patients measured by the symptom-medication scores demonstrated that C. nucifera
      pollen-allergic patients had significant (p < 0.005) clinical improvement after
      CPE-IT in comparison to placebo treatment. Serological study resulted a
      significant reduction (p < 0.001) of specific IgE and significant elevation (p <
      0.01) of specific IgG in post-therapeutic patients' sera which were correlated
      significantly (r = 0.45, p < 0.001); the changes of the above immunoglobulin
      levels in the placebo-treated patients were nonsignificant. However, there was no
      correlation between symptom-medication scores and changes in specific serum IgE
      or IgG levels.

PMID- 8292908
TI  - Perennial rhinitis subjects have altered vascular, glandular, and neural
      responses to bradykinin nasal provocation.
AB  - BACKGROUND: Bradykinin (BK) is known to stimulate vascular permeability by direct
      actions on vascular B2 receptors, and may stimulate nociceptive sensory nerves
      that recruit parasympathetic reflexes which induces glandular secretion.
      Differences in these responses may occur in allergic rhinitis. METHODS: The
      effects of bradykinin (BK) on nasal secretion in vivo were studied by unilateral
      BK nasal challenge in 8 normal subjects and 6 subjects with severe perennial
      allergic rhinitis. BK (0, 100, 1,000 nmol) were applied to one nostril
      (ipsilateral, IL) and saline lavage fluids collected separately from the IL and
      contralateral (CL) nostrils for analysis of total protein, albumin,
      glycoconjugates, and lysozyme. RESULTS: In both groups, BK induced significant
      dose-dependent IL total protein and albumin secretion, but significantly more
      total protein and albumin were stimulated in normal than rhinitis subjects after
      1,000 nmol BK. Glycoconjugate and lysozyme secretion was not significantly
      stimulated on either the IL or CL sides in normal subjects. However, in perennial
      allergic subjects, BK stimulated significant, dose-dependent glycoconjugate and
      lysozyme secretion on the IL side. Reflex effects were studied on the CL side.
      Normal subjects did not have significant CL glandular secretion. In contrast,
      rhinitis subjects secreted significantly higher amounts of total protein and
      glycoconjugate on the CL side after 1,000 nmol BK. There was no reflex-mediated
      albumin exudation in either group. CONCLUSIONS: These results indicate that in
      normal subjects BK stimulates predominantly vascular permeability, and that
      cholinergic reflexes do not significantly contribute to their BK-induced nasal
      secretion. In rhinitis subjects, BK again induced albumin exudation, but with
      less vascular permeability and greater glandular secretion than normal subjects
      on the challenged side. Only rhinitis subjects demonstrated significant
      contralateral reflex-mediated glandular secretion, and this response required the
      highest dose of BK. This suggests that BK is more adept at directly inducing
      vascular effects than glandular secretion of nociceptive nerve-parasympathetic
      reflexes. Alterations in BK-induced vascular permeability, glandular secretion,
      and neural reflexes occur in patients with severe perennial allergic rhinitis,
      changes suggestive of 'nasal hyperresponsiveness' to BK.

PMID- 8292909
TI  - Sinus aspirates and radiographic abnormalities in severe attacks of asthma.
AB  - We evaluated the occurrence of abnormalities in paranasal sinus radiographs in
      acute asthma by taking a radiograph of the sinuses of 110 consecutive patients
      admitted to a medical ward a total of 149 times for asthma. Maxillary sinus
      infection was assessed by taking aspirate from radiologically abnormal maxillary
      sinuses. An abnormal finding in any paranasal sinus was detected on 87% (130 of
      149) of admissions and the yield of maxillary aspirate was macroscopically
      mucous, purulent or mucopurulent in 60% (42 of 70) of aspirates. A positive
      bacteriological culture was obtained from 23 aspirates and a virus was detected
      in 15, there being 7 aspirates in which both a bacterium and a virus could be
      detected. Although the correlation between radiographic findings and the
      aspirates was not very close we conclude that radiographic abnormalities of the
      paranasal sinuses are common in acute asthma as are infections of maxillary
      sinuses with an abnormal radiographic finding. There is an obvious need to look
      for sinusitis when a patient with an exacerbation of asthma is being evaluated.

PMID- 8292910
TI  - [Alternative strategy for the diagnosis of HIV infection in sub-saharan Africa.
      Value of the sequential combination of the ELISA test and a 2nd generation rapid
      test].
AB  - The "conventional" algorithm for HIV testing based on the confirmation of all
      positive anti-HIV screening reactions by Western blot requires sufficient
      laboratory facilities and is expensive, that limits its use in developing
      countries, such as in subsaharian Africa. The apparition of second and third
      generation screening ELISA which are very sensitive and specific, as well as the
      development of rapid tests which are simple, visually read, and sufficiently
      sensitive and specific, has permitted the design of "alternative" strategy for
      HIV testing utilizing the association of 2 ELISA and/or rapid tests, in order to
      limit the use of a confirmatory assay. Alternative strategies are less expensive,
      yield generally very high sensitivity and specificity, and have proved to be
      valuable for African countries. In this study, 5 alternative strategies, using
      different associations of two second generation screening tests, one classical
      ELISA (Genelavia mixt) and one rapid test (Test PACK HIV-1/HIV-2 AB) have been
      retrospectively evaluated in the field in Bangui, Central African Republic, with
      a panel of 130 sera (prevalence of HIV infection: 42.7%). The strategy using two
      sequential screening tests (Test Pack HIV-1/HIV-2 AB following by Genelavia mixt)
      with the confirmation of discordant results by Western blot permitted to diagnose
      HIV-1 infection in Bangui with a sensitivity, a specificity and a positive
      predictive value of 100%, and to reduce the cost of more than 50% in comparison
      with the conventional strategy. Such an alternative strategy could be useful for
      the individual notification of HIV serology in Bangui.

PMID- 8292911
TI  - [Value of a mass vaccination campaign: measles cases in the hospital milieu in
      Brazzaville (Congo)].
AB  - In November 1986, Congo got up an immunization for measles of nine to 36 months
      old infants. The aim of this study was to compare the morbidness and the death
      rate of measles in a 20 months period before and after November 1986. The infants
      less than nine months old constituted 57.2% of the patients admitted after
      November 86 opposed to 19, 5% before November 86. The authors stand out for
      strategies that will let to immunize 97% of the infants.

PMID- 8292912
TI  - [Prevalence of 4 agents of sexually transmitted diseases in leukorrhea in Abidjan
      (Ivory Coast)].
AB  - 6,603 women with vaginal discharges were investigated for genital infection with
      four sexually transmitted diseases. Germs of vaginitis were isolated with
      prevalence as following: C. albicans 25%, G. vaginalis 17.4%, T. vaginalis 8.2%.
      Cervicitis with N. gonorrhoeae represented 3.2% of cases.

PMID- 8292913
TI  - [Estimation of the parasitological incidence and recovery rates of Plasmodium
      falciparum, P. malariae and P. ovale among children living in a malarial
      holoendemic zone in Congo].
AB  - The incidence and recovery rates of P. falciparum, P. malariae and P. ovale
      parasitaemia among schoolchildren from a Congolese village where malaria
      transmission is intense and perennial were studied from longitudinal data. Time
      intervals between sampling were two days, eight days, two weeks, two months and
      four months for the different surveys. Values derived from the model of BEKESSY
      et al. (1976) showed a great range of variation for P. falciparum (daily
      incidence rate h: 0.0119-0.0529; daily recovery rate r: 0.0043-0.0198) and for P.
      malariae (h: 0.0053-0.0103; r: 0.0115-0.0428). For P. ovale this model only
      fitted samples collected with a maximum time interval of eight days (h: 0.0048
      0.0058; r: 0.1400-0.1540). Although discrepancies between estimates may be
      explained in part by differences in malaria transmission, the results indicate
      that only short time intervals of sampling gave correct estimates of incidence
      and recovery rates in the population studied. The importance of this parameter
      has probably been insufficiently considered until now.

PMID- 8292914
TI  - [Evolution of Plasmodium falciparum drug sensitivity in Madagascar from 1982 to
      1993 and operational consequences].
AB  - Madagascar was one of the first African countries with reported chloroquine drug
      resistance of P. falciparum. Suspected as early as 1975, it was confirmed in
      1981. Hereafter, regular tests in vivo and in vitro have been performed and allow
      for a study of drug resistance development. In 742 standard in vivo tests at the
      dose of 25 mg/kg of chloroquine that were executed between 1983 and 1993, R I
      resistance levels could be found in 8.5% of cases, R II was found in 8.2%. No
      resistance at R III levels was detected. The overall situation for in vitro is
      equally favorable. In 406 tests 78% of samples proved sensitive. The
      investigations undertaken by the Pasteur Institute of Madagascar, by the
      Institute for Tropical Medicine and Epidemiology in Paris and by the Unit of
      Epidemiological Surveillance within the Malagasy Ministry of Health raise a
      number of questions: Taking to account the various causes for imprecision in
      measurement and in evaluation (variations in parasite density, microscopic
      detection levels, bio-availability of the drug) of the groups of R I and R II how
      significant are the variations observed in numbers and proportions of resistance
      levels R I and R II? How important are the effects of auto-medication? Can they
      be correctly evaluated by Bergquist's test? How explain the low level of drug
      resistance in a country close to East Africa, in which chemoprophylaxis has been
      widely practiced and in which insufficient dosage for treatment is common? The
      absence of R III resistance in vivo permit for chloroquine to remain the first
      line treatment for malaria in Madagascar.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8292915
TI  - [A strategy to control Trypanosomiasis due to Trypanosoma brucei gambiense in an
      endemic region of Zaire. Association of a serological test and early treatment of
      suspected cases. Preliminary results].
AB  - The authors report results obtained after combination of a serological diagnostic
      test and the early treatment of suspected cases (a person with a positive
      serological test without parasitological confirmation) in an area in Zaire where
      sleeping sickness caused by Trypanosoma brucei gambiense is endemic. The
      serological test used was Testryp CATT, having a very high sensitivity and quite
      a high specificity, which is easy to handle in the field and which permits
      results to be obtained on the spot. The treatment employed was a medication
      active in the first stage of the disease (hematolymphatic stage), safe to handle,
      with few side effects and easy to administer (diminazine). This strategy was
      applied for one year in the area from Fankana-Kalakitini in the Bandundu region
      in Zaire. The entire population was examined with the classical methods, combined
      with the serological test Testryp CATT, and this every six months. People
      positive for the serological test (but negative for the parasite) received one
      injection of the proposed medication; but people in whom parasites were found got
      classic treatment. After this period, we were able to demonstrate a clear decline
      in the incidence rate of new cases (parasite positive), but also in
      seropositivity rates in the general population. The authors believe that in a
      circumscribed area where the disease is endemic, the combination of a serological
      test and early treatment of suspected cases can rapidly diminish the incidence of
      the disease to an acceptable level.

PMID- 8292917
TI  - [Existence in Tunisia of Necator americanus (Nematoda, Ankylostomidae)].

PMID- 8292916
TI  - [Morbidity and histo-endoscopic study of Schistosoma mansoni bilharziasis in
      Nkolbisson (Cameroon)].
AB  - This study confirms the efficiency of bilharzia eradication campaigns at
      Nkolbisson. The authors recommend rectal mucosa biopsy of symptomatic patients in
      whom several investigations have turned out negative.

PMID- 8292918
TI  - [Gingival lesions in ameloblastoma: value of preoperative biopsy].
AB  - Ameloblastomas are common in Niger. Their main risk is recurrence, which nearly
      always follows inadequate surgery: these tumors require radical excision followed
      with mandibular graft. A preoperative diagnosis is therefore indispensable. X-ras
      are non-specific. In Niger, the danger of osteomyelitis makes surgical biopsies
      dangerous. The attention is brought to the existence of gum lesions in 8 cases of
      ameloblastoma in Nigerian patients. Their biopsy may provide the diagnosis in
      quick and safe conditions.

PMID- 8292919
TI  - [Epidemiological and clinical aspects of Buruli ulcer in Ivory Coast. 124 recent
      cases].
AB  - A prospective study during 28 months at the Regional Hospital Center of Bouake
      (Ivory Coast) allows to gather 124 cases of Buruli ulcer. Today, this atypical
      cutaneous mycobacteriosis is in full expansion in West Africa. The pathogen
      agent, Mycobacterium ulcerans, causes, by its toxin, a subcutaneous necrosis
      often extended, followed by an ulceration which clinical characteristics are
      sufficient for the diagnostic. The endemic progression reason may not be caused
      by the modification of patients receptivity, but rather by the natural
      environment modification. In particular, the improving number of some soft water
      fish (Tilapia) which could have a germ tank.

PMID- 8292920
TI  - [Eosinophilic meningitis. Review of the literature and a new case originating
      from Reunion Island].
AB  - We report a case of eosinophilic meningitis occurring in a European patient
      living in the Reunion Island. We review the literature and discuss the diagnosis
      of angiostrongylosis.

PMID- 8292921
TI  - [Clinical value of C-reactive protein, alpha 1-glycoprotein acid and transferrin
      assay in homozygous sickle cell disease].
AB  - Two acute phase reactants (C-reactive protein: CRP and alpha 1-acid glycoprotein:
      alpha 1-AGP) and transferrin (Tf) levels change were measured in order to
      evaluate their clinical or prognostic value during the vaso-occlusive crisis.
      Measurements were performed in normal controls, painful crisis with or without
      treatment and during steady state. Immunochemical determinations indicate that
      markedly acute inflammation occurred in sickle cell painful crisis, as revealed
      CRP and alpha 1-AGP levels. Compared to controls, during periods of steady state
      in the absence of any intercurrent condition, a lesser but significative increase
      of alpha 1-GPA was observed. Transferrin level remained lower and did not
      sufficient to discriminate between crisis and steady state. Compared to the
      vasodilatator drug effect, non steroidal anti-inflammatory drug showed more
      efficiency in the sickle cell disease inflammatory process. Taken together, these
      findings indicate that serial determinations of CRP, alpha 1-GPA and Tf may be
      helpful in monitoring the course of sickle cell disease and response to
      treatment. Then, non steroidal anti-inflammatory drugs appear necessary to reduce
      the length of the sickle cell crisis.

PMID- 8292922
TI  - [Notes on the phlebotomus of Air (Niger)].
AB  - 238 phlebotomine sandfly belonging to seven species have been collected in four
      localities of Niger, in the Air mountain range. Phlebotomus bergeroti was the
      dominant species in animal bait and in collections inside dwellings. Some
      attention has to be paid to P. alexandri, a recognized vector of kala-azar
      elsewhere.

PMID- 8292923
TI  - ["To be blind", blindness between an epidemiological and a sociological
      definition].
AB  - From an epidemiological point of view, blindness refers to a visual acuity
      inferior to 1/20 in each eye. Though such a definition is necessary for the
      installation of public health programs, it is insufficient as far as the
      elaboration of actions aimed at prevention and rehabilitation are concerned.
      Qualitative data reveal that a similar physical deficiency is lived in various
      ways according to precise social context. In addition to the physical handicap
      objectively defended and to its social interpretation, the same must also be
      analysed in the light of another important linking factor; the individuals'
      social status and specific task and obligations of various groups in a given
      population. Considered together, these factors provide a better understanding of
      the social condition of blind persons, their economic and matrimonial resulting
      in the conception of appropriate health programs.

PMID- 8292924
TI  - Outcome of treating hypothyroidism.

PMID- 8292925
TI  - Sigmoidoscopy: a necessary practice?

PMID- 8292926
TI  - Helping individuals protect their health. What you can tell your patients. Great
      Lakes Health Effects Program.

PMID- 8292927
TI  - Radiology rounds. Congenital diaphragmatic hernia.

PMID- 8292928
TI  - Practicalities of family medicine. Residents changing the system.

PMID- 8292929
TI  - Congestive heart failure with sinus rhythm. Audit of digoxin therapy in a family
      medicine teaching unit.
AB  - The literature was reviewed for evidence of digoxin efficacy and for indicators
      of positive digoxin response in chronic congestive heart failure with normal
      sinus rhythm. Practice in a family medicine teaching unit was audited based on
      this review. Most patients in this study were treated appropriately. Several (22%
      to 36%), however, were treated incorrectly with digoxin.

PMID- 8292930
TI  - Programs for international medical graduates.
AB  - Medical graduates from other countries provide health care in many regions of
      Canada; yet differences in training standards can cause problems. A recent survey
      looked at the requirements of provincial licensing bodies and the preresidency
      programs of Canadian faculties of medicine. Quebec, Ontario, and Manitoba provide
      such programs, which differ in length, content, and evaluation process. McGill
      has recently launched a more focused program.

PMID- 8292931
TI  - Patients, friends, and relationship boundaries.
AB  - When patient and physician are close friends, both professional and personal
      relationships can suffer. Jointly exploring and setting explicit boundaries can
      help avoid conflict and maintain these valuable relationships. This is
      particularly important when the physician practises in a small community where
      such concurrent relationships are unavoidable.

PMID- 8292932
TI  - Boundary issues. What do they mean for family physicians?
AB  - Clear boundaries between physicians and patients help prevent abusive behaviour.
      Enforced boundaries help physicians fulfil their legal, ethical, and professional
      tasks. We review common elements in boundary violations: role reversal, secrecy,
      double binds, and indulgence of professional privilege. We also outline the legal
      and licensing issues of boundary violations and offer examples of nine
      boundaries.

PMID- 8292933
TI  - Death of a child.
AB  - The death of a small child from a terminal illness is an uncommon but influential
      event in a family physician's career. Through dialogue with colleagues and
      friends, self-reflection, and acknowledgment of some of the difficulties, this
      experience can stimulate personal growth.

PMID- 8292934
TI  - Denial among cancer patients. Tips and traps.
AB  - The coping mechanisms used by patients diagnosed with cancer play a role in their
      well-being and, therefore, influence their quality of life and possibly even
      their survival. We review the characteristics of one of these mechanisms, denial,
      and suggest an approach to dealing with denying patients.

PMID- 8292935
TI  - Deeper diagnosis. Multiple determinants of an illness experience.
AB  - This paper identifies the multiple determinants of a complex illness experience
      and describes the difficult process of diagnosis and management. The crucial
      coordination and integration role of the family physician is explained. The
      perspectives of the family physician, the consulting psychologist, and the
      patient are elucidated. Interventions by physicians from various specialties are
      identified and explored. Psychological determinants, including those rooted in
      the patient's history, are revealed in parallel with the physiological
      manifestations.

PMID- 8292936
TI  - McGill-medicine student initiative. Project report.

PMID- 8292937
TI  - The true wealth of our nation.

PMID- 8292939
TI  - AIDS: global lessons from a global epidemic.

PMID- 8292938
TI  - How to improve monitoring and forecasting of disease patterns.

PMID- 8292940
TI  - Poor children in rich countries.

PMID- 8292941
TI  - Refugee children.

PMID- 8292942
TI  - Left handedness.

PMID- 8292943
TI  - The knowledge disease.

PMID- 8292944
TI  - Was Young's syndrome caused by exposure to mercury in childhood?
AB  - OBJECTIVE: To determine whether the incidence of chronic sinusitis, bronchitis,
      or bronchiectasis in men with obstructive azoospermia (Young's syndrome) has
      fallen in men born after 1955 when calomel (mercurous chloride) was removed from
      teething powders and worm medication in the United Kingdom. DESIGN: A prospective
      study of aetiological factors in subfertile men with epididymal obstruction
      operated on between 1975 and 1993. SETTING: Central London. SUBJECTS: 274 men
      with obstructive azoospermia undergoing epididymovasostomy; date of birth was
      recorded and illness in childhood, persistent nasal or respiratory symptoms, and
      previous urinary or genital infection were asked about. MAIN OUTCOME MEASURE:
      Site of epididymal block and association with possible aetiological factors,
      related to date of birth. RESULTS: 146 men had hold up in the head of the
      epididymis (capital blocks): 119 (82%) had Young's syndrome, and 11 gave a
      definite history of pink disease (mercury intoxication) in childhood. 128 had
      obstruction lower down towards the tail of the epididymis (caudal blocks): 64
      (50%) had a history of genital or urinary infection, and only three had Young's
      syndrome; none had had pink disease. The incidence of Young's syndrome fell
      significantly from 114 (50%) of 227 men born up to 1955 to eight (17%) of 47 men
      born since then. CONCLUSIONS: The decline in incidence of Young's syndrome in
      those born after 1955 is similar to that observed with pink disease, suggesting
      that both conditions may have had a similar aetiology--mercury intoxication.

PMID- 8292945
TI  - Multicentre randomised double bind crossover trial on contamination of
      conventional ties and bow ties in routine obstetric and gynaecological practice.
AB  - OBJECTIVE: To assess level of contamination of neckwear worn by gynaecologists
      and obstetricians during routine working week. DESIGN: Multicentre randomised
      double blind crossover trial. Participants wore the same conventional ties for
      three days in one week and bow ties for the same period in second week. SETTING:
      Two teaching and three district general hospitals in the midlands, Wales, and
      north England. SUBJECTS: 15 registrars and senior registrars. INTERVENTIONS: A
      swab soaked in sterile saline was taken from specific area on ties at end of
      first and third working days and sent in transport medium for culture on
      chocolatised blood and MacConkey agar for 48 hours. MAIN OUTCOME MEASURES: Level
      of bacteriological growth assessed semiquantitatively (0 for no contamination;
      for heavy contamination) after swabs had been cultured. At end of study the
      participants completed a questionnaire to assess their attitude toward wearing
      different types of necktie. RESULTS: 12 doctors (80%) completed the study.
      Although bow ties were significantly less contaminated at end of first working
      day (z = -2.354, p = 0.019), this difference was not maintained; there was no
      difference in level of contamination on third day. Level of contamination did not
      increase between first and third day of wearing the same garment. One of the 10
      doctors who returned the questionnaire found the bow tie very uncomfortable. All
      participants would consider wearing a bow tie if it proved to be less
      contaminated than a conventional tie. CONCLUSIONS: Although a significant
      difference in contamination was established between conventional and bow ties on
      first day of study, this difference was not confirmed on third day and there is
      unlikely to be any real association between tie type and bacterial contamination.
      Because of its negative image and difficulty to tie, the bow tie will probably
      remain a minority fashion.

PMID- 8292946
TI  - Is Friday the 13th bad for your health?
AB  - OBJECTIVE: To examine the relation between health, behaviour, and superstition
      surrounding Friday 13th in the United Kingdom. DESIGN: Retrospective study of
      paired data comparing driving and shopping patterns and accidents. SUBJECTS:
      Drivers, shoppers, and residents. SETTING: South West Thames region. MAIN OUTCOME
      MEASURES: Numbers of vehicles on motorways; numbers of shoppers in supermarkets;
      and hospital admissions due to accidents. RESULTS: There were consistently and
      significantly fewer vehicles on the southern section of the M25 on Friday the
      13th compared with Friday the 6th. The numbers of shoppers were not significantly
      different on the two days. Admissions due to transport accidents were
      significantly increased on Friday 13th (total 65 v 45; p < 0.05). CONCLUSIONS:
      Friday 13th is unlucky for some. The risk of hospital admission as a result of a
      transport accident may be increased by as much as 52%. Staying at home is
      recommended.

PMID- 8292947
TI  - The Midas touch?
AB  - OBJECTIVE: To test the hypothesis that GP trainees are worth their weight in
      gold. DESIGN: Data collected from 100 consecutive patients analysed with
      reference to practice statistics, fees, and allowances. SETTING: General
      practice, Edinburgh. RESULTS: In the year April 1992 to April 1993 the trainee
      saw 3439 patients, who were worth over 18,000 pounds in capitation fees. The
      training grant is 4570 pounds, the trainee performed child health surveillance
      worth 1000 pounds, and items of service fees earned more than 8500 pounds. The
      trainee brought over 31,000 pounds into the practice in one year. CONCLUSION:
      Trainees are (almost) worth their weight in gold.

PMID- 8292948
TI  - Urine culture in the diagnosis of colovesical fistula.

PMID- 8292949
TI  - Charcot and his visits to Britain.

PMID- 8292950
TI  - Medical women in the first world war--ranking nowhere.

PMID- 8292951
TI  - A summons to Carthage, December 1943.

PMID- 8292952
TI  - Alexander Hepburne Macklin: physician, polar explorer, and pioneer.

PMID- 8292953
TI  - Walking across Antarctica.

PMID- 8292954
TI  - The dangers of sledging.

PMID- 8292955
TI  - A commission of lunacy, mad doctors, and happy hunting.

PMID- 8292956
TI  - Cycling for health: forty years ago.

PMID- 8292957
TI  - Mongolia: a health system in transition.

PMID- 8292958
TI  - Travelling as a doctor.

PMID- 8292959
TI  - Information sharing: getting journals and books to developing countries.

PMID- 8292960
TI  - Cover story: Kitaj's "Heart attack".

PMID- 8292961
TI  - Big brother is looking after your health.

PMID- 8292962
TI  - Consultatio epistulae--the way forward?

PMID- 8292963
TI  - Ensuring the robustness of targeted briefs.

PMID- 8292964
TI  - Paradigm, parameter, paralysis of mind.

PMID- 8292965
TI  - Deprivation and health.

PMID- 8292966
TI  - Metachromatic leukodystrophy: two sides of a coin.

PMID- 8292967
TI  - HIV experimental vaccines based on the iscom technology using envelope and GAG
      gene products.
AB  - In previous experiments gp160 incorporated into iscom was shown to induce
      neutralizing antibodies to the homologous as well as the heterologous isolates of
      HIV-1 (Akerblom et al., AIDS Res., 1991). In the present work we have
      incorporated into iscoms three defined recombinant DNA products of HIV-1. The
      carboxy-terminal part of gp120 expressed in E. Coli-PB-1; a chimera containing
      parts of both p24 and p15 expressed in E. coli-GAG; and baculovirus gp160 cloned
      in baculovirus and produced in insect cells. Immune responses were induced by the
      iscom preparations to the homologous antigen as well as to defined recombinant
      products and to the synthetic peptide RP135 (aa 304-328) harboring a neutralizing
      epitope. Sera from mice immunized with PB1-iscoms and gp160 (baculo) iscoms were
      tested in a syncytie inhibition assay. The serum from a mouse immunized with PB1
      iscoms reacted strongly with the synthetic peptide RP135 and also neutralized the
      homologous isolate HIV-1/IIIB with a neutralization titer of 1/64. Three gp160
      (baculo) iscom antisera were tested, of which two reacted strongly with the
      synthetic peptide RP135 but did not neutralize the homologous isolate HIV-1/IIIB.
      High serum titers were induced in mice by the gp160 iscoms (2 micrograms) to
      homologous antigen and the recombinant DNA E. coli construct p121 covering part
      of gp41. The ceilings of the antibody responses were reached after two
      immunizations. The PB1- and GAG-iscoms required three immunizations to reach the
      ceiling of the antibody response.

PMID- 8292968
TI  - Therapeutic efficacy of a high-affinity anticarcinoembryonic antigen monoclonal
      antibody (COL-1).
AB  - COL-1 is a murine IgG2a monoclonal antibody (MAb) with a high affinity (1.4 x
      10(9) M-1) for carcinoembryonic antigen (CEA) and no detectable reactivity for
      CEA-related antigens, such as nonspecific cross-reacting antigen (NCA) and normal
      fecal antigen (NFA). 125I-labeled COL-1 IgG was shown to efficiently and
      specifically target the LS-174T human colon carcinoma xenograft in athymic mice.
      Dose titration studies in this same model with 131I-labeled COL-1 demonstrated
      reduction of tumor growth rate when 300 microCi of the immunoconjugate was used
      (0.005 > p > 0.001). Administration of higher levels as a single dose led to
      increased toxicity. Dose fractionation experiments with 131I-COL-1 demonstrated
      the ability to administer much higher levels of the immunoconjugate with little
      or no toxicity, which resulted in a greater therapeutic efficacy. For example,
      three fractions of 200 microCi of 131I-COL-1 given at weekly intervals (for a
      total of 600 microCi) resulted in the substantial reduction (p < 0.0005) of the
      growth of established tumors in 100% (7/7) of mice, and in no evidence of tumor
      growth in 71% (5/7) of mice, at the end of the 63-day observation period. These
      results thus demonstrate the potential therapeutic efficacy for radiolabeled COL
      1 in clinical trials and demonstrate the principle of the advantage of dose
      fractionation protocols for this immunoconjugate.

PMID- 8292969
TI  - Granulocyte-macrophage colony-stimulating factor given before dose-intensive
      cyclophosphamide, etoposide, and cisplatin (DICEP).
AB  - Substantial increases in dose-intensity of chemotherapy yield a severalfold
      increase in complete remission rates and durable responses in several types of
      malignant disease. Hematopoietic colony-stimulating factors decrease the duration
      of the resultant severe neutropenia but optimal dosing regimens of these
      cytokines have not yet been determined. This study was designed to explore the
      use of both yeast-derived and E. coli-derived GM-CSF given pre- and
      postchemotherapy with an intensive combination chemotherapy regimen. The
      chemotherapeutic regimen consisted of cyclophosphamide 5000 mg/m2, etoposide 1500
      mg/m2, and cisplatin 150 mg/m2 (DICEP). Patients receiving either yeast-derived
      GM-CSF (6.5 days) or E. coli-derived GM-CSF (6.0 days) had a shorter duration of
      severe granulocytopenia with an absolute granulocyte count below 300/microL than
      patients receiving no GM-CSF (11.0 days, p = 0.0001). Administration of GM-CSF
      for 6 days immediately preceding DICEP did not further shorten the duration of
      cytopenia. E. coli-derived GM-CSF given at doses above 5 micrograms/kg was poorly
      tolerated and offered no hematologic advantage. Lower doses (3 micrograms/kg) of
      the E. coli product were better tolerated but still produced more toxicities than
      yeast-derived GM-CSF. The yeast-derived product produced no local skin reactions
      and decreased the incidence of nonhematologic and all grade 3 or 4 toxicities
      compared to the control group.

PMID- 8292970
TI  - Synthesis of prothymosin alpha deduced from nucleotide sequence of the murine
      cDNA and its effect on the impaired T lymphocytes of uremic patients.
AB  - The complete murine prothymosin alpha molecule (110 residues) except for the N
      terminal methionine deduced from the cloned cDNA has been synthesized by a solid
      phase method. Peptide synthesis was performed manually by the stepwise solid
      phase method using the base-labile Fmoc group for protecting the alpha-amino
      group. The peptide was assembled on a p-alkoxybenzyl alcohol resin. After the
      last coupling step, the Fmoc group was removed with 50% piperidine in DMF. The
      peptide resin was treated with thioanisole-o-cresol in TFA, and then purified by
      gel filtration, ion-exchange column chromatography and high-performance liquid
      chromatography. A 2.9-mg sample of a highly purified peptide was finally
      obtained. The overall yield of the synthesis was less than 1%, based on the amino
      acid content of the starting Fmoc-Asp (OtBu)-resin. The synthetic peptide was
      found to have a restoring activity on low-E-rosette-forming lymphocytes after
      incubation of peripheral blood from uremic patients with the synthetic peptide.
      This peptide exhibited far stronger restoring effect than that of our synthetic
      thymosin alpha 1.

PMID- 8292971
TI  - Synthesis of deacetyl-thymosin beta 12 and examination of its immunological
      effects on the impaired T and B lymphocytes in uremic patients.
AB  - Deacetyl-thymosin beta 12 was synthesized in a conventional manner by assembling
      six peptide fragments followed by deprotection with 1 M trifluoromethanesulfonic
      acid-thioanisole (molar ratio, 1:1) in trifluoroacetic acid in the presence of m
      cresol and dimethyl-selenium. Incubation of peripheral lymphocytes isolated from
      uremic patients with the synthetic deacetyl-thymosin beta 12 showed an enhancing
      effect on the reduced beta lymphocytes but had no restoring effect on the
      impaired blastogenic response of T lymphocytes.

PMID- 8292972
TI  - Leukocyte inhibitory factor (LIF) potentiates human macrophage aggregation and
      activation responses to calcium ionophore A23187 and directly induces leukotriene
      B4 and thromboxane A2 release.
AB  - Aggregation studies have become a useful criterion for analyzing leukocyte
      motility and activation in vitro. The T-cell-derived lymphokine human leukocyte
      inhibitory factor (LIF) is a modulator of many important polymorphonuclear (PMN)
      functions in addition to aggregation such as chemotaxis, lysosomal degranulation,
      phagocytosis, bactericidal killing, augmented antibody-dependent cellular
      cytotoxicity (ADCC), induction of neutrophil Fc-gamma, complement type-1 and FMLP
      receptors, and production of superoxide and H2O2. Our investigations focused on
      the ability of LIF to modulate the aggregation of macrophages (MO) induced by
      calcium ionophore A23187. The ionophore A23187 directly induced potent
      aggregation of macrophages, which was markedly enhanced when the cells were
      pretreated with LIF. However, the addition of LIF in the absence of other
      costimuli did not directly induce MO aggregation. LIF was shown to enhance PMN
      aggregation induced by N-formyl-Met-Leu-Phe (FMLP), but did not augment the
      aggregation of FMLP-stimulated macrophages, indicating a cellular specificity of
      aggregation-inducing costimuli following LIF priming. Additional cytokines
      examined for possibly inducing MO aggregation were interleukin-1 (IL-1), tumor
      necrosis factor-alpha (TNF), and interleukin-6 (IL-6); all proved to be incapable
      of inducing aggregation directly, nor did they enhance the effect of A23187
      ionophore on macrophage aggregation. Additionally, we found that LIF can directly
      stimulate MO to activate specific pathways of the arachidonic acid cascade,
      inducing the synthesis and release of thromboxanes and leukotriene B4. LIF did
      not augment the potent ability of A23187 to induce increased production of LTB4
      or TxA2 by human MO. These new results coupled with our previously published data
      indicate that LIF can enhance the activation of both MO and PMN leukocytes when
      exposed to either A23187 or FMLP, respectively. Moreover, these data suggest that
      LIF can contribute directly to monocyte-macrophage leukocyte activation, in
      addition to PMN activation, during inflammatory responses, resulting in greater
      cell aggregation, activation, and specific proinflammatory arachidonic acid
      product release.

PMID- 8292973
TI  - Characterization of melatonin binding sites in human peripheral blood
      neutrophils.
AB  - In this paper we show the presence of 2-[125I]melatonin binding sites in human
      neutrophils (hN). The specific binding of melatonin to hN cells and hN membranes
      was dependent on time and temperature, stable, saturable, and reversible. In
      competition studies, the specific binding of radioactive melatonin to hN cells or
      hN membranes was inhibited by increasing concentrations of native melatonin.
      Scatchard analysis showed the existence of a single class of binding sites with a
      Kd of 2.1 and 7.1 microM for hN cells and hN membranes, respectively. The binding
      capacity was of 84 and 132 pM for hN cells and hN membranes, respectively. The
      affinity of the binding sites for melatonin suggests that they may be relevant in
      studies on the pharmacological properties of melatonin in regulating human
      neutrophil activity.

PMID- 8292974
TI  - Effect of the natural bioflavonoid antioxidant silymarin on superoxide dismutase
      (SOD) activity and expression in vitro.
AB  - The in vitro effects of the bioflavonoid antioxidant silymarin on the expression
      and activity of superoxide dismutase (SOD) enzyme was studied in erythrocytes and
      lymphocytes from patients with chronic alcoholic liver disease. In vitro
      incubation with the agent in a concentration corresponding to the usual
      therapeutic dosage markedly increased the SOD expression of lymphocytes as
      measured by flow-cytofluorimetry following staining with monoclonal anti-Cu/Zn
      SOD antibody and FITC-conjugated anti-mouse Ig, as well as erythrocyte and
      lymphocyte SOD activities. The data indirectly suggest that antioxidant activity
      might be one of the important factors in the hepatoprotective action of this
      bioflavonoid.

PMID- 8292975
TI  - IL-5 and IL-5 receptor expression on human eosinophils in relation to eosinophil
      activation.

PMID- 8292976
TI  - [The effect of the plant toxin ricin on the cellular structure of human
      hypophyseal tumors].

PMID- 8292977
TI  - [The effect of temperature on the kinetics of the alpha 1-adrenergic reaction of
      rat vas deferens smooth muscles].

PMID- 8292978
TI  - [The effect of brief hypoxia on cognitive processes and the neuronal correlates
      in monkeys].

PMID- 8292979
TI  - [Differences in stress resistance during agonistic interactions between male and
      female great gerbils (Rhombomys opimus licht)].

PMID- 8292980
TI  - [Experimental study of the role of sensory information in gray rat behavior].

PMID- 8292981
TI  - [Interaction of mutations in the SUP45 (SUP1) gene in saccharomyces yeasts and
      their effect on protein structure].

PMID- 8292982
TI  - [Change in the optical spectra of phenylalanine during its radiation-chemical
      transitions].

PMID- 8292983
TI  - Pharmaceutical care in long-term treatment. European Society of Clinical
      Pharmacy.

PMID- 8292984
TI  - Effect of h-EGF and h-EGF 1-48 on histamine-stimulated gastric acid secretion in
      rats and monkeys.
AB  - The effect of human epidermal growth factor (h-EGF) and its derivative human
      epidermal growth factor 1-48 (h-EGF 1-48) on histamine-stimulated gastric acid
      secretion was studied in monkeys and rats. In monkeys, both h-EGF and h-EGF 1-48
      given intravenously (i.v.) in a stepwise manner and in doses ranging from 0.01 to
      10 nmol/kg, gradually suppressed gastric acid secretion. At the highest dose
      tested, both compounds essentially abolished gastric acid output. In the same
      animals, i.v. administration of 1 nmol/kg of h-EGF or h-EGF 1-48 caused an
      inhibition of gastric acid output that reached a peak at 90 and 60 min after the
      administration of h-EGF or h-EGF 1-48 respectively. After this maximum gastric
      inhibitory effect, a gradual return toward pre-injection values was observed. In
      rats, after subcutaneous (sc) administration, both h-EGF and h-EGF 1-48 dose
      dependently inhibited histamine-stimulated gastric acid output as measured 60 min
      after the administration of the compounds. The maximum inhibitory activity on
      gastric acid output, observed at a dose of 100 nmol/kg, was 74.4% and 76.0% for h
      EGF and h-EGF 1-48 respectively. The same dose of both compounds, however, failed
      to significantly inhibit gastric acid secretion when administered orally. In all
      the studies h-EGF 1-48 showed activity and potency comparable to h-EGF.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8292985
TI  - Neural and muscular control functions of the gut in odontocetes: morphologic
      evidence in beaked whales and beluga whales.
AB  - The present data provide some new and unique, gastrointestinal morphologic
      findings in two species of toothed whales, the Cuvier's beaked whale (Ziphius
      cavirostris) and the beluga or white whale (Delphinapterus leucas), which are
      discussed relative to their atypical feeding behavior and alimentary tract
      functions. Specifically, the findings show myenteric neural modifications and
      muscularis externa structural specializations which may support voluntary and
      involuntary fore- and hindgut behavior. Histologic evidence of intercalation-like
      striations in the gastric and colonic musculature was discovered, as well as an
      unusual massive size of the colonic myenteric plexuses. These observations, which
      are not evident in terrestrial mammalian gastrointestinal tracts, may help
      explain the unusual upper gastrointestinal tract motility such as ingestion-by
      sucking in the absence of prehensile teeth and processing of ingesta in a multi
      compartmentalized pyloric stomach. Further, the hindgut modifications may help
      explain the animal's acute, rectal discharge escape mechanism, likened to squid
      inking, which seems to be an evolved function of some cetaceans.

PMID- 8292986
TI  - Neuronal receptors for caerulein in gallbladder.
AB  - Release of [3H]-acetylcholine ([3H]ACh) and muscle contractions in response to
      caerulein was measured and recorded simultaneously from isolated guinea-pig
      gallbladder. Caerulein (5 x 10(-9) M) enhanced the release of [3H]ACh and the
      contractions. Tetrodotoxin (10(-6) M) inhibited the caerulein-induced release of
      [3H]ACh by only 30%. Proglumide and loxiglumide (CR 1505) antagonized the effect
      of caerulein on both ACh-release and contractions. Neither proglumide nor
      loxiglumide affected the DMPP-induced contractions and the ACh release. The
      results suggest not only muscular but also neuronal receptors for caerulein in
      guinea-pig gallbladder.

PMID- 8292987
TI  - Nicotine and gastric ulcers in stress.
AB  - Chronic nicotine treatment worsens stomach mucosal damage by cold (4 degrees C)
      and restraint (stress): it dose- and time-dependently intensifies stress-evoked
      gastric glandular ulceration, mast cell degranulation and motility. Nicotine 50
      micrograms/ml drinking water, given ad libitum to female Sprague-Dawley rats for
      10 days, increases the sensitivity of the isolated stomach strip to acetylcholine
      induced contractions; atropine abolishes this action. The isolated anococcygeus
      muscle from nicotine-treated male rats shows increased sensitivity to
      noradrenaline-induced contractions, but not to those by acetylcholine.
      Hexamethonium or atropine pretreatment antagonises stress-induced gastric effects
      in nicotine-drinking rats. Muscarinic M1- and M2-, but not M3-, receptor block
      (by pirenzepine, AF-DX 116BS and HHSiD, respectively) inhibits stress ulcer
      formation in female rats. Although tobacco smoking has been reported to increase
      free radical formation, mucosal xanthine oxidase which initiates free radical
      formation is uninfluenced by nicotine; antagonising this enzyme (by allopurinol)
      or hydroxyl free radical scavenging (by dimethylsulfoxide) does not lessen the
      effect of nicotine on stress-evoked ulceration. The findings suggest that chronic
      nicotine treatment produces partial ganglionic blockade of the vagal nerve which
      leads to muscarinic receptor supersensitivity. This phenomenon contributes
      significantly to the ulcer-worsening mechanism; muscarinic M1- and M2-receptors
      appear to be involved. The gastric ulcer-aggravating effect of nicotine in
      stressed rats appears not to be due to increased free radical formation.

PMID- 8292988
TI  - Effect of the cold pressor test in healthy and hyperacid subjects.
AB  - The aim of this study was to estimate the effects of the cold pressor test (CPT)
      on hemodynamic changes and to analyze the differences in the changes between
      normal and hyperacid subjects. Twelve healthy volunteers and 12 hyperacid
      patients were studied. The different hemodynamic parameters (basic impedance, ZO;
      heart rate, HR; systolic and diastolic blood pressure, RRs and RRd; ventricular
      ejection time, VET; stroke volume, SV; cardiac output, CO; rate-pressure-product,
      RPP) were measured and calculated with the impedance cardiographic method (ICG).
      The changes of hemodynamic parameters (HR, RRs, RRd, VET, SV, CO, RPP) were well
      recorded by this method. The data were analyzed with unpaired t-tests and the
      multivariate statistical method, pattern recognition by independent multicategory
      analysis (PRIMA). There were significant differences in changes of ZO, HR (P <
      0.05), RRs, RRd, SV, CO and VET (P < 0.01) and subjects in the normal and
      hyperacid groups could be well separated by the PRIMA method.

PMID- 8292989
TI  - Prevention of stress-induced gastric ulcers by mu- and delta-opioid agonists in
      the rat.
AB  - The effects of intraperitoneal and intracerebroventricular administration of mu-
      and delta- selective opioid receptor agonists (DAGO and DPDPE, respectively) on
      gastric lesions, were investigated in cold-restraint-stressed rats. DAGO and
      DPDPE, peripherally and centrally administered, induced a significant gastric
      protection. Naloxone prevented the effects of both opioids whereas naltrindole
      prevented the gastric protection induced by DPDPE but not that by DAGO. The
      results suggest that mu- and delta-opioid agonists prevent gastric damage induced
      by stress through an involvement of both central and peripheral mu- and delta
      opioid receptor subtypes.

PMID- 8292990
TI  - Effects of GABAergic drugs on ethanol-induced gastric lesions.
AB  - Different classes of GABAergic drugs--baclofen, GABA, muscimol, Na-valproate, Mg
      valproate and diazepam--were tested per os on ethanol-induced gastric lesions in
      rats. The GABAB agonist baclofen failed to affect gastric susceptibility to
      ethanol damage, while all the other compounds exerted a dose-dependent inhibition
      on haemorrhagic-necrotic lesions. This effect was not significantly reversed by
      the specific GABAA antagonist bicuculline, suggesting it to be independent from
      GABAA receptors. The blockade of prostaglandin synthesis by indomethacin
      significantly decreased the gastroprotective action of GABA, Na- and Mg
      valproate, but did not antagonize the effect of muscimol and diazepam. Gastric
      juice volume and pH showed remarkable differences between the various treatments.

PMID- 8292991
TI  - Inhibition of the spore polar filament extrusion of the microsporidium,
      Encephalitozoon hellem, isolated from an AIDS patient.
AB  - Spores of the microsporidian parasitic protozoan Encephalitozoon hellem were
      purified and incubated at 37 degrees C in a solution with an electrolyte
      composition similar to that of mammalian extracellular fluid, and in solution in
      which the calcium had been replaced with 0.2 mM EGTA. Polar filament extrusion
      (germination) was monitored by both scanning electron microscopy and light
      microscopy. Germination was pH-dependent, with optima at pH 7.4 and 9.5, and was
      significantly greater in the presence of medium calcium. Hydrogen peroxide caused
      a concentration-dependent increase in germination that was also reduced in a
      calcium-free medium. Four agents were found to inhibit spontaneous and H2O2
      stimulated polar filament extrusion: the microfilament disrupter, cytochalasin D;
      the microtubule disrupter, demecolcine; the calcium channel blocker, nifedipine;
      and the antifungal agent, itraconazole. These results are consistent with the
      existence of a calcium-channel-mediated step, and requirements for an F-actin-
      and for a tubulin-containing element in the germination process of the spore of
      this parasite. Nifedipine, cytochalasin D and itraconazole all have different
      sites of action and were therefore able to potentiate one another when used in
      paired combination to inhibit germination.

PMID- 8292992
TI  - Production and characterization of monoclonal antibodies against a highly
      immunogenic fraction of Entamoeba histolytica (NIH:200) and their application in
      the detection of current amoebic infection.
AB  - Six monoclonal antibodies (MAbs) were produced against a highly immunogenic
      fraction derived by the chromatographic separation of the soluble preparation of
      axenic Entamoeba histolytica (strain NIH:200) trophozoites. Isotype
      characterization of the six MAbs revealed that four belonged to the IgM class and
      one each to the IgG1 and the IgG2a subclasses. The immunoreactivity patterns and
      the specificity of the MAbs with homologous and heterologous antigens were
      analyzed by the enzyme-linked immunotransfer blot technique and by the enzyme
      linked immunosorbent assay. The MAbs reacted intensely with isolates of E.
      histolytica (strain NIH:200 as well as a local isolate MX1) but showed no
      reactivity with Entamoeba coli, Iodamoeba butschlii, Endolimax nana, Entamoeba
      hartmanni, free-living amoeba (Acanthamoeba harticolus) and other enteric
      parasites. Using the IgG1 MAb as a detecting antibody, a polyclonal-monoclonal
      antibody-based enzyme-linked immunosorbent assay was developed for the detection
      of E. histolytica antigens in stool samples of infected patients. The detection
      limit of the assay was 8 ng of amoebic antigen. This test was found to be
      specific and sensitive and yielded 100% positive results in cases with amoebiasis
      but did not react with controls included in the evaluation. The MAb-based enzyme
      linked immunosorbent assay developed in this study will be an important test for
      the diagnosis of E. histolytica in the feces of infected humans; however, the
      limitation of the test is the inability to discriminate the pathogenic status of
      the amoeba detected in the stool.

PMID- 8292993
TI  - Molecular genetic distinction of Pneumocystis carinii from rats and humans.
AB  - Pneumocystis carinii from rats and from humans were compared with respect to
      electrophoretic karyotype, presence of DNA sequences known to be repeated in rat
      derived P. carinii, overall DNA sequence homology, and the sequences at two
      genetic loci. The organisms from each host species were different in each
      respect. Neither of two repeated DNAs from rat-derived P. carinii was found in
      the genome of human-derived organisms, and total DNA from rat-derived P. carinii
      failed to hybridize to human-derived P. carinii DNA. The sequences of the alpha
      tubulin genes from the two P. carinii were strikingly different and the base
      composition of the alpha-tubulin gene from rat-derived P. carinii was rich in
      adenine and thymine, while the base composition of this gene from human-derived
      P. carinii was rich in guanine and cytosine. The sequence from the 18S rRNA gene
      of human-derived P. carinii was twice as divergent from that of rat-derived P.
      carinii as the sequence from the corresponding region of Candida albicans was
      from that of Candida tropicalis. These data show that rats and humans can harbor
      distinct types of P. carinii that are sufficiently different to suggest that P.
      carinii from the two hosts could be different species.

PMID- 8292994
TI  - Relationship between spatial pattern of basal bodies and membrane skeleton
      (epiplasm) during the cell cycle of Tetrahymena: cdaA mutant and anti-membrane
      skeleton immunostaining.
AB  - Microtubular basal bodies and epiplasm (membrane skeleton) are the main
      components of the cortical skeleton of Tetrahymena. The aim of this report was to
      study functional interactions of basal bodies and epiplasm during the cell cycle.
      The cortex of Tetrahymena cells was stained with anti-epiplasm antibody. This
      staining produced a bright epiplasmic layer with a dark pattern of unstained
      microtubular structures. The fluorescence of the anti-epiplasm antibody
      disappeared at sites of newly formed microtubular structures, so the new basal
      body domains and epiplasmic layer could be followed throughout the cell cycle.
      Different patterns of deployment of new basal bodies were observed in early and
      advanced dividers. In advanced dividers the fluorescence of the epiplasmic layer
      diminished locally within the forming fission line where the polymerization of
      new basal bodies largely extincted. In wild type Tetrahymena, the completion of
      the micronuclear metaphase/anaphase transition was associated with a transition
      from the pattern of new basal body deployment and epiplasm staining of the early
      divider to the pattern of the advanced dividers. The signal for the fission line
      formation in Tetrahymena (absent in cdaA1 Tetrahymena mutationally arrested in
      cytokinesis) brings about 1) transition of patterns of deployment of basal bodies
      and epiplasmic layer on both sides of the fission line; and 2) coordination of
      cortical divisional morphogenesis with the micronuclear mitotic cycle.

PMID- 8292995
TI  - Purification and characterization of phospholipase C preferentially hydrolysing
      phosphatidylcholine in Tetrahymena membranes.
AB  - A phospholipase C (PLC) activity that preferentially hydrolyses
      phosphatidylcholine to diacylglycerol and phosphorylcholine was found to be
      present in Tetrahymena pyriformis, strain W and most of its activity was
      recovered in the membrane fraction. This enzyme was extracted with 1% Triton X
      100 from the membrane fraction and purified to apparent homogeneity by sequential
      chromatographies on Fast Q-Sepharose, hydroxyapatite HCA-100S, Mono Q and
      Superose 12 gel filtration columns. The purified enzyme had specific activity of
      2083 nmol of diacylglycerol released/mg of protein/min for
      dipalmitoylphosphatidylcholine hydrolysis. Its apparent molecular mass was 128
      kDa as determined by SDS-polyacrylamide gel electrophoresis and was 127 kDa by
      gel filtration chromatography, indicating that the enzyme is present in a
      monomeric form. The enzyme exhibited an optimum pH 7.0 and the apparent Km value
      was determined to be 166 microM for dipalmitoylphosphatidylcholine. A marked
      increase was observed in phosphatidylcholine hydrolytic activity in the presence
      of 0.05% (1.2 mM) deoxycholate. Ca2+ but not Mg2+ enhanced the activity at a
      concentration of 2 mM. This purified phospholipase C exhibited a preferential
      hydrolytic activity for phosphatidylcholine but much less activity was observed
      for phosphatidylinositol (approximately 9%) and phosphatidylethanolamine
      (approximately 2%).

PMID- 8292996
TI  - Development of Trypanosoma (M.) theileri in tabanids.
AB  - Thus far the life cycle of Trypanosoma (Megatrypanum) theileri has not been
      studied. We collected tabanids during the mass hatching, when only few tabanids
      are infected with trypanosomes. Tabanids were caught immediately after attacking
      a bait cow to serve as controls or after they had been allowed to engorge on the
      Trypanosoma (M.) theileri-infected cow. Tabanids were kept in the laboratory and
      used to study the developmental cycle of T. (M.) theileri in the tabanid gut.
      From day 1 to day 10 the presumably unfed controls and the engorged tabanids were
      dissected and cytological smears made from the mid- and hindgut. In total 2.6%
      (1/38) of the controls and 39% (23/59) of the engorged tabanids were positive for
      trypanosomes in the 1991 season. From day 1 to day 4 after engorgement
      trypanosomes were found in the midgut. Epimastigotes with a length of 29 microm
      on day 1 after infection multiplied by inequal division to form smaller
      epimastigotes of 26 microm on day 3. On day 4 morphologically indistinguishable
      trypanosomes of 21 microm total length were found in both mid- and hindgut. From
      day 5 to day 10 trypanosomes were found only in the hindgut in which the
      transformation to metacyclics was demonstrated, i.e., epimastigotes transformed
      to amastigote stages of 5 microm in total length.

PMID- 8292997
TI  - Directed positioning of micronuclei in Paramecium tetraurelia with laser
      tweezers: absence of detectible damage after manipulation.
AB  - Possible covert damage from the use of the laser optical force trap (laser
      tweezers) to reposition micronuclei in Paramecium tetraurelia was assessed by
      measuring proliferation rates and postautogamous survival and mutation rates of
      cells after laser manipulations. No differences in subsequent daily proliferation
      rates among laser manipulated and various control classes of cells were seen.
      Similarly, the rates of postautogamous lethality and of "slow growth mutations"
      after repositioning of both micronuclei were not different from such rates in
      unmanipulated controls. In spite of extensive manipulations of micronuclei by the
      laser tweezers, there is no evidence of any damage induced by these
      manipulations. The laser tweezers therefore appears to be a tool of benign effect
      upon living cells, with tremendous potential use in many cell and developmental
      biological investigations.

PMID- 8292998
TI  - Aminotransferase and the production of alanine during hyperosmotic stress in
      Paramecium calkinsi.
AB  - When Paramecium calkinsi encounter hyperosmotic stress, intracellular free
      alanine increases. In vivo assays indicate that the reaction catalyzed by alanine
      aminotransferase contributes to the build up of alanine in response to
      hyperosmotic shock. 14C-pyruvate is converted to 14C-alanine in cells grown
      axenically at 200 mosm. When shifted to 600 mosm, the rate of conversion of
      pyruvate to alanine increases, and conversion at either 200 or 600 mosm is
      blocked by 1 mM aminooxyacetic acid (AOA), an inhibitor of aminotransferase.
      Intracellular free alanine increase is partially inhibited by AOA, and AOA
      prevents cells living in fresh water from acclimating to higher salinities, an
      indication that the increase in intracellular alanine is physiologically
      significant.

PMID- 8292999
TI  - Characterization of Pneumocystis carinii preparations developed for lipid
      analysis.
AB  - Pneumocystis carinii organisms were isolated from viral antibody-negative rats
      that had been infected by intratracheal intubation of organism preparations
      tested negative for common bacteria and fungi. Infection scores of lungs from
      infected animals at the time of parasite isolation was > 5 (100-1,000
      organisms/oil immersion field). Electron microscopy of heavily infected lungs
      revealed that the pathogens adhered to Type I pneumocytes and to each other,
      resulting in obstructions up to several cell layers thick, which extended into
      the alveolar lumen. Protocols for purifying the organisms were developed to
      optimize separation from each other and from host cells, and to optimize
      preparation purity, recovery efficiency, and organism viability. The study tested
      mucolytic agents, sieving, various centrifugation speeds, lysis of host cells by
      osmotic shock and filtration through membranes of different pore diameter. Final
      preparations contained no intact host cells as determined by light microscopy.
      Only minor amounts (< 5%) of host debris were detected by electron microscopy.
      Most organisms and their pellicles were ultrastructurally intact but no longer
      adhered to one another. The final preparation was characterized biochemically by
      quantitation of the specific lung surfactant marker surfactant protein A, which
      indicated > 99.5% purity. The total non-P. carinii protein in the final
      preparation (< 6%, depending on the level of infection) was estimated by the
      protein content of pelletable material resulting from processing uninfected lungs
      in an identical manner. Elimination of free cholesterol and phospholipids from
      host lung tissue was monitored during the purification process. Exogenous
      stigmasterol, added as an extracellular marker, decreased during the purification
      process and was undetectable in the final organism preparation. Yields of 10(8)
      10(9) organisms/rat were routinely obtained. Viability, assessed by the calcein
      acetoxymethyl ester-propidium iodide assay, was 80-95%.

PMID- 8293000
TI  - Serotypic variation among isolates of Ichthyophthirius multifiliis based on
      immobilization.
AB  - Efforts have been made to determine whether surface antigens could be used as
      biochemical markers to define strain differences in the parasitic ciliate
      Ichthyophthirius multifiliis. In previous studies, a wild-type isolate designated
      G1 was found to have surface proteins analogous to the immobilization antigens of
      Paramecium and Tetrahymena; rabbit antiserum against this strain immobilizes
      homologous cells in vitro. It has now been shown for two additional
      Ichthyophthirius isolates (designated G1.1 and G2) that immobilization antigens
      are both present and serologically distinct. Proteins of similar size, which
      cross-react in Western blots with rabbit antisera against immobilization antigens
      of the G1 strain, are nevertheless found in the G1.1 and G2 isolates. As shown by
      Southern blotting analysis, the G1.1 and G2 strains also contain genomic DNA
      sequences which hybridize with an immobilization antigen cDNA from G1 when probed
      under conditions of reduced stringency. The serotypic differences in
      immobilization between I. multifiliis isolates appear to be stable over time and
      provide a means of discriminating strains. In addition to providing a basis for
      comparative studies, the work described here has implications for the development
      of vaccines against this important fish parasite.

PMID- 8293001
TI  - Genes encoding antigenic surface glycoproteins in Pneumocystis from humans.
AB  - Pneumocystis is a eukaryotic microbe that causes pneumocystosis, an AIDS
      associated pneumonia. Pneumocystosis also occurs in many other mammalian species,
      and animal-derived organisms have been extensively utilized in Pneumocystis
      research. Pneumocystis from diverse hosts contain a large glycoprotein (gpA/MSG)
      on the surface. Antibodies elicited against gpA/MSG of Pneumocystis from humans
      sometimes cross-react with epitopes on proteins of similar size from Pneumocystis
      from other host species. Here we report the isolation and partial sequence of two
      presumptive gpA/MSG genes from human-derived Pneumocystis. The cloned human
      derived Pneumocystis gpA/MSG genes and predicted peptides were different from
      those previously isolated from Pneumocystis from rats and ferrets. The genome of
      human-derived Pneumocystis contained multiple copies of sequences related to the
      two cloned gpA/MSG genes.

PMID- 8293002
TI  - [Transgenic rats for HLA-B27 and human beta 2 microglobulin: a model of
      spondyloarthritis].

PMID- 8293003
TI  - [Is inclusion body myositis a true myositis?].

PMID- 8293004
TI  - [Antigliadin antibodies in rheumatoid arthritis].
AB  - To investigate the potential role of gliadin in the pathophysiology of some cases
      of rheumatoid arthritis (RA), the authors assayed antigliadin antibodies (AGAb)
      in RA patients. They used an ELISA to determine AGAb levels in 100 RA patients, a
      group of RA-free controls with a variety of inflammatory diseases (ID), and a
      group of controls with noninflammatory diseases (NID). The authors found no
      significant increase in AGAb titers in the RA patient group as compared with
      either control group. Only nine patients with RA had detectable levels of AGAbs,
      which were of the IgG type in seven cases and of the IgA type in two cases. RA
      patients with and without AGAbs were compared. Patients with AGAbs more often had
      signs of autoimmune disease including sicca syndrome, positive tests for
      rheumatoid factor, and positive tests for antinuclear antibodies.

PMID- 8293005
TI  - [Serum hyaluronic acid in osteoarthritis].
AB  - In this prospective study, serum hyaluronate (SH) was assayed using a radiometric
      method (Pharmacia) in 73 osteoarthritis patients and 39 controls. All assays were
      performed between 8 h 00 and 9 h 00 a.m. because SH levels exhibit circadian
      variations. SH levels were significantly higher in patients with osteoarthritis
      than in controls (92 +/- 66 micrograms/l and 39 +/- 21 micrograms/l,
      respectively, p = 0.0001). Among 50 patients with osteoarthritis, including 29
      with knee involvement and 21 with hip involvement, SH levels were not correlated
      with morning stiffness, duration of symptoms, Lequesne's algofunctional index,
      erythrocyte sedimentation rate, C-reactive protein, severity of roentgenographic
      changes in the affected knee or hip, disease extension, or severity. The lack of
      any relationship between changes in SH levels and Lequesne's is index values in
      25 patients or between SH levels and joint space narrowing evaluated
      retrospectively in 16 patients, as well as the prompt return to high SH levels
      after arthroplasty and synovectomy in 14 patients with hip joint osteoarthritis,
      suggest that this potential marker is not useful for monitoring osteoarthritis in
      a single joint.

PMID- 8293006
TI  - [Idiopathic osteonecrosis of the internal femoral condyle. Prognostic elements
      and role of different treatments].
AB  - In this retrospective study, 36 patients with a mean age of 72 years (range 60 to
      82) underwent surgical treatment for osteonecrosis of the medial femoral condyle.
      The procedure consisted in tibial valgus osteotomy in 18 cases, unicompartmental
      arthroplasty in 15 cases, and total knee arthroplasty in 3 cases. Analysis of a
      number of factors (size of the lesion, knee deformity as assessed by goniometry,
      condition of the joint...) demonstrated that valgus osteotomy performed to reduce
      the load experienced by the necrotized area was effective in preventing extension
      of the lesion and development of a synovial pannus; furthermore, this procedure
      ensured preservation of the range of motion of the knee and, when performed
      sufficiently early, prevented deterioration of the medial femorotibial joint
      space. On the basis of our data, it can be concluded that arthroplasty is
      warranted only in patients aged 75 years or more and in those with extensive
      necrosis; unicompartmental arthroplasty should be performed whenever possible;
      total arthroplasty should be used only when the size of the lesion precludes
      secure implantation of a single-compartment device.

PMID- 8293007
TI  - [Determination of the instantaneous center of rotation of the shoulder using the
      ELITE system. Application to the study of normal and pathological abduction].
AB  - The authors determined the in vivo displacement of the instantaneous center of
      rotation (ICR) of the shoulder from data supplied by an optoelectronic system
      (ELITE System) which uses a specifically designed software program to achieve 3
      dimensional analysis of abduction. The study involved 10 control subjects and 20
      patients suffering from a periarticular disorder of the shoulder capsule
      retraction in 10 cases and rotator cuff tears before and after rehabilitation in
      10 cases. This method provides an objective assessment of humeral head
      misalignment in relation to the glenoid cavity induced by the periarticular
      shoulder disorder and of the realignment achieved through rehabilitation. The
      proposed ICR calculation technique is entirely harmless for the patient in
      (particular because it requires no radiation analysis).

PMID- 8293008
TI  - [Is it possible to identify women with rapid vertebral bone loss during
      menopause? Result of a longitudinal study of 92 women at the onset of menopause].
AB  - Low bone mass is the main risk factors for osteoporosis. The role of the rate of
      bone loss following cessation of menses is more difficult to evaluate. We
      prospectively studied vertebral bone loss in 92 women six months to three years
      after cessation of menses in order to determine the clinical and biological
      characteristics of the subgroup of subjects with accelerated bone loss. Clinical
      characteristics, hormone assay results, and values of the main biochemical
      markers of bone turnover were recorded at the initial evaluation and correlations
      between these parameters and the rate of bone loss were investigated. Serial
      measurements of vertebral bone density were performed using dual photon
      absorptiometry. Mean duration of the observation period was 31 +/- 13 months.
      Mean rate of bone loss was -1.66% per year (range 1.6% to 7.7%). In women with
      accelerated vertebral bone loss i.e., a greater than 2.5% decrease in bone
      density per year (25th centile), there were trends towards lower values for body
      mass index and weight (non-significant) and a significantly higher urinary
      calcium/urinary creatinine ratio (p < 0.05) as compared with the rest of the
      study group. Rate of bone loss was weakly correlated (p < 0.05) with body mass
      index (r = 0.22) and with the urinary calcium/urinary creatinine ratio (r = 0.23)
      but demonstrated no correlations with osteocalcin levels or serum alkaline
      phosphatase activity. In conclusion, none of the clinical features or laboratory
      parameters studied proved capable of reliably predicting the rate of vertebral
      bone loss in individual women shortly after cessation of menses.

PMID- 8293009
TI  - [New immunologic treatment of rheumatoid arthritis].
AB  - Rheumatoid arthritis is a heterogeneous disease for which no satisfactory therapy
      is available. Conventional treatments have nonselective immunological effects.
      Cyclosporin A ensures partially selective immunotherapy. Recently developed
      selective immunotherapy methods target CD4+ T-cells and their receptors, antigen
      presenting cells including macrophages with surface expression of class II HLA
      antigens, antigen peptide(s) presented by macrophages, class II HLA antigens or T
      cell receptors. T-cell suppression can be achieved using monoclonal antibodies or
      the still experimental T-cell vaccination. Monoclonal antibodies against
      activation antigens, including CD4, CD5, CD25 (interleukin 2 receptor), CD52, and
      adhesion molecules, have been investigated in animal studies and open trials in
      humans. Monoclonal antibodies directed against class II HLA antigens or antigen
      presenting cells have been studied in animals. Peptide immunotherapy has yielded
      promising results in a variety of animal models. Other immunotherapy methods
      target cytokines, especially those which promote inflammation. Encouraging
      preliminary results have been obtained in rheumatoid arthritis patients with
      interleukin-1 receptor antagonists and monoclonal antibodies against tumor
      necrosis factor alpha. Problems raised by selective immunotherapy for rheumatoid
      arthritis and potential indications are discussed.

PMID- 8293010
TI  - [Association of rheumatoid arthritis and Kaposi disease. Apropos of a case
      arising after intraarticular corticotherapy].
AB  - A 66 year old Corsican HLA A2 and DR5-positive male with moderately active
      seropositive destructive rheumatoid arthritis developed Kaposi's sarcoma after
      intraarticular administration of corticosteroids. He had no history of oral
      corticosteroid therapy, organ transplantation, AIDS, or cancer. Chlorambucil
      proved ineffective but the outcome was spontaneously favorable following
      discontinuation of oral corticosteroid therapy initiated after the development of
      the skin lesions. Six previous reports of concomitant rheumatoid arthritis and
      Kaposi's sarcoma were found. All six cases occurred following systemic
      corticosteroid therapy. The high incidence of rheumatoid arthritis and the small
      number of patients with rheumatoid arthritis and Kaposi's sarcoma suggest that
      concomitant occurrence of the two conditions may be fortuitous. However, the
      responsibility of corticosteroid therapy, which preceded development of Kaposi's
      sarcoma in every case, cannot be ruled out.

PMID- 8293011
TI  - [Intradural metastasis. Value of magnetic resonance imaging].
AB  - Imaging a 70 year old man with lymph node metastases from an adenocarcinoma
      developed cauda equina syndrome. The diagnosis of intradural metastatic disease
      was established on the basis of magnetic resonance imaging with gadolinium
      injection which visualized diffuse nodules in contact with the nerve roots.

PMID- 8293012
TI  - [Malignant lymphoma in rheumatoid arthritis treated by low doses of
      methotrexate].
AB  - The authors report a case of non-Hodgkin's malignant lymphoma which developed in
      a patient under low-dose methotrexate for rheumatoid arthritis. Although
      rheumatoid arthritis without immunosuppressive therapy may be associated with an
      increased incidence of malignant lymphoma, the immunosuppressive effects of
      methotrexate may further promote the development of malignant lymphoma.

PMID- 8293013
TI  - [Progressive paraparesis, complication of acquired pagetic synostosis of the
      cervical vertebrae. 2 cases].
AB  - Two cases of pagetic cervical intervertebral synostosis with spinal cord
      compression are reported. Computed tomography and magnetic resonance imaging
      enabled detailed analysis of pagetic bone structure and relationships between the
      fused spinal segment and spinal cord. Few similar cases have been reported and
      most authors have advocated conservative therapy with calcitonin and/or
      diphosphonates, with surgery only in cases unresponsive to pharmacotherapy.

PMID- 8293014
TI  - [Peripheral erosive arthritis and Crohn disease].

PMID- 8293015
TI  - [Destructive hip osteoarthritis in palmo-plantar pustulosis. Apropos of a new
      case].

PMID- 8293016
TI  - [Rheumatoid arthritis and collagenous colitis. Apropos of a new case].

PMID- 8293017
TI  - Observing and imitating the formation of object classes during the second year of
      life.
AB  - The developmental origins of overt object classification are still poorly
      understood, but one factor that may be informative and facilitative of
      classification during the second year is observing adults group similar objects.
      A pretest-posttest design with modeling and control groups was used to assess the
      impact of modeling on deferred imitation of groupings based on object similarity.
      Children at three ages (12, 18, and 24 months) observed an adult produce class
      groupings and alignments of objects. By 18 and 24 months, there was significant
      deferred imitation of object groupings. There was virtually no effect at 12
      months. Moreover, only at 24 months were classified sets spatially aligned. The
      results indicate that observing adult classification will at least facilitate
      object grouping during the latter part of the second year, and that it may
      promote the use of spatial alignments as organizing devices or as modes of
      depicting object classes.

PMID- 8293018
TI  - [Sensitivity and diagnostic value of mental load in a secondary task on tapping
      rate].
AB  - When executed concurrently with a primary task, finger tapping performance is
      commonly interpreted as an indication of the primary task mental workload. Higher
      load during tapping induces an increase in mean or variability of intertap
      intervals. Finger tapping sensitivity was tested with series of 13 taps at a
      tapping rate of one tap every two seconds. Concurrent primary task required
      subjects to search for a target item, presented after each tap, in a three digit
      memory set memorized before each series. Processing load was varied by including
      letter targets amongst positive and negative digit targets. Letter target
      recognition should require less processing than digit recognition. Results show
      mean intertap intervals for letter targets to be shorter than for negative digit
      targets. Furthermore, recognition of negative digit targets induces a longer mean
      intertap interval than positive targets. These data suggest that continuous
      finger tapping is a sensitive index of the mental workload originating from
      working memory processing requirements. However, analysis of practice data show
      that development of strategies at performing the dual task may mask the
      sensitivity of the finger tapping task.

PMID- 8293019
TI  - Gender differences in horizontality and verticality representation in relation to
      initial position of the stimuli.
AB  - Research on gender differences in the ability to represent horizontality in the
      water-level task has suggested that failure in some women may be connected with
      responding while envisioning the upright container as shifting to a tilted
      position and holding liquid in motion, rather than imaging that the container has
      reached the tilted position and holds still liquid. The present experiment
      attempted to eliminate such faulty conceptualization by solely presenting
      containers that had already reached a stable, tilted position. College students
      of both sexes were submitted either to the modified, static presentation of the
      water-level task or to the standard, dynamic format using both upright and tilted
      positions. The subjects were also submitted to corresponding plumb-line tasks
      requiring verticality representation. In addition, they rated the vividness of
      their movement imagery. Contrary to prediction, women's proficiency was not
      higher under the static format of the water-level and plumb-line tasks. However,
      as expected, men's achievement was independent from presentation format. Men
      surpassed women under both static and dynamic formats. Finally, performance was
      not correlated with movement imagery. Lack of a presentation effect on women's
      performance was attributed to the fact that a number of women presumed an element
      of motion when responding, even though stationary stimuli were shown.

PMID- 8293020
TI  - A model for conceptual processing of naturalistic scenes.
AB  - Are there fundamental differences in the way in which a list of pictures and a
      list of words are processed? We report three experiments that examine serial
      position effects for rapidly-presented naturalistic scenes. The experiments
      provide a basis for comparison with the U-shaped serial position curve and list
      length effect which typically result from verbal learning experiments. In
      contrast to the U-shaped verbal serial position function, our results show a flat
      function at the beginning serial positions and a recency effect which is small
      and limited to the last serial position. There is a set-size effect. Results
      suggest that the processing leading to a memory representation for visual stimuli
      such as pictures and linguistic stimuli such as words is qualitatively
      dissimilar. The findings can be accounted for by a serial processing model whose
      main parameter is the probability that the subject will switch attention from one
      picture to the next.

PMID- 8293021
TI  - Managed care and mental health: the silencing of a profession.
AB  - Rapid change in the organization and financing of health care has created a
      bewildering and threatening climate for psychotherapists. Fearful of exclusion
      from preferred provider and health maintenance organizations, and aware that
      patient advocacy is interpreted as antagonism to these organizations' goals, many
      therapists have fallen silent, acquiescing to practices they do not support.
      Crystallization of these practices into policy and law is now imminent. It is
      crucial that therapists reclaim their authority, speaking out on behalf of
      current and future patients as well as the concealed constituency of historically
      disenfranchised persons for whom psychotherapy has provided a voice.

PMID- 8293022
TI  - Comorbidity of DSM-III-R eating disorders and personality disorders.
AB  - The purpose of this study was to assess the relationship of eating disorders to
      personality disorders. Two hundred subjects were independently administered the
      Structured Clinical Interview for DSM-III-R (SCID) and the Personality Disorder
      Examination (PDE) face-to-face by two experienced clinicians. One hundred forty
      six also completed the Personality Diagnostic Questionnaire-Revised (PDQ-R).
      Rates of personality disorder among patients with and without eating disorders
      were determined by each of the three instruments. Comorbidity between bulimia
      nervosa and anorexia nervosa and a conservative estimate of individual Axis II
      disorders was examined. Eating disorders with and without personality disorders
      were compared on age at onset and two measures of illness severity. Results
      indicate that the association, in general, between personality disorders and
      eating disorders varies by diagnostic method. Bulimia nervosa, however, is
      associated with borderline personality disorder and anorexia nervosa with
      avoidant personality disorder. Eating disorders with personality disorders are
      characterized by chronicity and low levels of functioning compared with eating
      disorders without personality disorders.

PMID- 8293023
TI  - Problem drinking and symptoms of disordered eating in female high school
      students.
AB  - Research on the relationship between problem drinking and disordered eating in
      adolescent girls has produced conflicting results. This study examines this
      relationship using a state-of-the-art inventory for measuring eating disorder
      symptoms and a standardized inventory for detecting problem drinking among
      adolescents. Two hundred thirty-four female high school students (mean age = 15.5
      years) completed the Adolescent Drinking Index and the Eating Disorder
      Examination Questionnaire. Girls diagnosed with an eating disorder were twice as
      likely to be problem drinkers than girls who were not diagnosed with an eating
      disorder. Regression analysis and comparisons of problem drinkers and non-problem
      drinkers point to the central role of body image concerns and dieting in the
      association of alcoholism and disordered eating among adolescent girls.
      Prospective studies are needed to explore the mechanisms underlying the links
      between drive for thinness and problem drinking.

PMID- 8293024
TI  - Eating behavior in binge eating disorder.
AB  - In order to examine the eating behavior of individuals with the newly proposed
      diagnosis, binge eating disorder (BED), standardized meals were served to 20
      obese women, 10 with BED and 10 without BED. When asked to binge eat from a
      multiple-item array of foods, obese subjects with BED consumed significantly more
      calories than did obese subjects without BED. Significant differences between the
      two groups were also found on several of the self-report measures.

PMID- 8293025
TI  - Themes of death: Helmut Thoma's "Anorexia nervosa" (1967)--a research note.
AB  - In the recent literature on eating disorders, little attention is usually given
      to the possible role played by heightened death fears and anxieties and failed
      death transcendence in the dynamics of patients who suffer from anorexia and
      bulimia nervosa. For reasons that remain unclear, early texts and articles in the
      literature do address death themes, particularly as they are discernible from
      patients' dreams and nightmares. Thoma's 1967 text Anorexia Nervosa may be
      interpreted as giving further illustration to this thesis.

PMID- 8293026
TI  - History of eating disorders in female patients with obsessive-compulsive
      disorder.
AB  - The prevalence of eating disorders was assessed in a casenote study of 105 female
      patients with obsessive-compulsive disorder (OCD). A previous history of anorexia
      nervosa was found in 12 (11%). Patients with a previous history of eating
      disorders (OCD-AN) had an earlier onset of OC symptoms than other patients. Among
      OCD-AN patients, the anorexia nervosa and obsessive-compulsive disorders had a
      similar age of onset. The comorbidity of the two syndromes among females may
      point to common vulnerability factors. Patients with early onset OCD may be at
      increased risk of developing eating disorders. The assessment of OCD in young
      female patients should include a careful check for evidence of eating disorders.

PMID- 8293027
TI  - Body image and food consumption: three laboratory studies of perceived calorie
      content.
AB  - Three studies are reported that measured body image and mood changes consequent
      to the consumption of a milkshake that differed in perceived number of calories
      (high vs. low). The pilot investigation on normal-weight college females produced
      an interaction between perceived calorie content (PCC) and time of testing-
      subjects who received the high-calorie shake overestimated body size and were
      more dysphoric at posttest than subjects who received the low calorie shake.
      Study 2 provided a credibility check that the pilot investigation failed to
      include and replicated the interaction between PCC and time of testing for size
      estimation accuracy. The effect was also found for an attitudinal measure of body
      satisfaction, but only a main effect of time eventuated for the mood measure.
      Study 3 compared subjects who differed on exercise status (runners vs. sedentary
      controls). In general, runners were less negatively affected by the high-calorie
      shake than controls, however, none of the hypothesized three-way interactions
      among group, PCC, and time of testing were significant. The findings are
      discussed in terms of the need to further experimentally investigate factors that
      affect different aspects of body image.

PMID- 8293028
TI  - Weight concern should not be a necessary criterion for the eating disorders: a
      polemic.
AB  - Problems associated with the inclusion of weight concern as a necessary and
      defining criterion for the diagnosis of the eating disorders are reviewed. It is
      proposed that the substitution of the criterion of eating restraint that is
      overinvested by the subject might have advantages for both clinical
      classification and for research.

PMID- 8293029
TI  - Fat phobia: measuring, understanding, and changing anti-fat attitudes.
AB  - We examined fat phobia, defined as a pathological fear of fatness, by
      constructing the Fat Phobia Scale, determining its reliability and validity,
      examining correlates of fat phobia, and using a treatment approach designed to
      decrease fat phobia. Study 1 describes the development of the Fat Phobia Scale, a
      50-item, modified 5-point semantic differential scale. Subjects (974 females and
      117 males) completed the scale; factor analysis yielded six factors. Respondents
      who are average weight, female, younger, have more than a high school education,
      or are nonmedical professionals are more likely to have fat phobic attitudes.
      Study 2 examines fat phobic attitudes of women (N = 40) who had negative feelings
      about their bodies. Subjects completed the Fat Phobia Scale before and after a
      treatment approach designed to reduce their feelings of responsibility for
      fatness. Total scores on the Fat Phobia Scale and scores on all six factors
      decreased significantly, indicating a decrease in fat phobia.

PMID- 8293030
TI  - Aging-related concerns and body image: possible future implications for eating
      disorders.
AB  - We observed a direct correlation between aging-related concerns about the
      appearance and Drive for Thinness (Eating Disorders Inventory [EDI]), among males
      (n = 71) (Pearson r = .36, p < .01) and females (n = 102) (Pearson r = .44, p <
      .01) from a nonclinical sample of shoppers. Among the women there was a direct
      correlation between the belief that weight loss is associated with youthful looks
      and both Drive for Thinness (EDI) (Pearson r = .44, p < .01) and Body
      Dissatisfaction (EDI) (Pearson r = .27, p < .01). Concerns about the cutaneous
      stigmata of aging, a commonly recognized sign that a person is older, correlated
      directly with Drive for Thinness (Pearson r = .27, p < .01) and Body
      Dissatisfaction (Pearson r = .38, p < .01) among the women. These correlations
      were all obtained after statistically controlling for the effects of age and body
      mass index. Our empirical observations may have important future implications in
      the development of eating disorders, as our society continues to place an
      inordinate value on youthful looks.

PMID- 8293031
TI  - Outcome in adolescent eating disorders.
AB  - A consecutive series of 60 adolescent patients with eating disorders was followed
      up after a mean period of 58 months. At intermediate follow-up, 4 (6.65) of the
      former patients were reported deceased, and 6 could either not be traced or
      refused to cooperate. Follow-up assessment revealed the following diagnostic
      pattern in 50 patients who were followed up: 5 (10%) of the patients still
      suffered from anorexia nervosa, 2 (4%) from anorexia nervosa with bulimia, 7
      (14%) from partial syndromes of anorexia nervosa, 2 (4%) from partial syndromes
      of bulimia nervosa, and 34 (68%) had recovered. Questionnaire findings indicated
      that the improvements that occurred during inpatient treatment were intact at
      follow-up. No significant findings were revealed by the analysis of a large scale
      of potential prognostic factors.

PMID- 8293032
TI  - Anorexia in the elderly--an annotation.
AB  - Genuine anorexia nervosa starting in the elderly is thought relatively uncommon.
      Some previously reported cases may have been elderly depressives with loss of
      appetite rather than true eating disorder. The condition also has to be
      distinguished from "late onset" anorexia in mature but younger women. Two
      illustrative patients are briefly reported. Some possible psychological
      mechanisms in this syndrome are discussed in the context of the relatively small
      total number of previously reported single cases.

PMID- 8293033
TI  - Anorexia nervosa in an elderly man.
AB  - Anorexia nervosa (AN) rarely develops after the age of 30 years, and rarely
      occurs in men. We report a case of chronic AN in a 72-year-old man, who reported
      a 20-year history of extreme low body weight, persistent fears of obesity, and
      feelings of being fat even at 93 lb. Also reported were episodes of self-induced
      vomiting, laxative abuse, and excessive exercising. Patient's scores on a battery
      of questionnaires were also consistent with a diagnosis of AN.

PMID- 8293034
TI  - Bulimia nervosa in the Chinese.
AB  - Typical DSM-III-R bulimia nervosa with self-induced vomiting was found in 2 women
      of Hong Kong Chinese origin and a Chinese man from Malaysia. All 3 cases had a
      family history of obesity. In 2 of the cases a period of weight gain and in the
      third case frank obesity preceded the onset of the eating disorder. Cultural
      transition seemed to play an important part in the onset and maintenance of the
      eating disorder.

PMID- 8293035
TI  - Transient neurogenic stuttering.
AB  - The occurrence of a transient neurogenic stutter in a male anorexic patient is
      described. The stutter developed following a prolonged period of starvation, and
      during refeeding the patient recovered from the stuttering behavior. The patient
      was not receiving any drugs known to cause stuttering, and it is postulated that
      the stutter developed as a result of the gross impairment of brain function
      secondary to chronic starvation. A review of the literature has failed to reveal
      any information on anorexia nervosa as a cause of neurogenic (acquired)
      stuttering.

PMID- 8293036
TI  - Selective attention to food and body shape words in dieters and restrained
      nondieters.
AB  - The current study investigated the presence of an attentional bias towards the
      processing of body shape and food-related material amongst noneating disordered
      women. Subjects carried out a computer-based Stroop color-naming task in which
      they had to name the colors of food-related words, body shape-related words, and
      two sets of matched neutral words. Significant color-naming disruptions of both
      food and body shape-related material were found for highly restrained eaters,
      irrespective of whether they were currently dieting. There were no reliable
      differences in color-naming times found for low to medium restrained eaters.
      Procedural differences probably account for the failure of previous studies to
      reveal such effects in nonclinical groups.

PMID- 8293037
TI  - Differentiation of BA-HAN-1C rhabdomyosarcoma cells is controlled by a pertussis
      toxin sensitive signaling pathway.
AB  - BA-Han-1C rat rhabdomyosarcoma cells grow with a transformed phenotype and do not
      differentiate efficiently. Here, we report that these cells can be induced with
      pertussis toxin (PTX) to rapidly express the myogenin gene and form terminally
      differentiated myotubes. Potential targets for the effect mediated by PTX are G
      alpha i-2 and G alpha i-3 proteins, the only inhibitor GTP-binding proteins
      expressed in these cells. While G alpha i-2 is found at the plasma membrane, G
      alpha i-3 is predominantly associated with Golgi vesicles and endoplasmic
      reticulum, suggesting that it may regulate protein trafficking. Differentiation
      of BA-Han-1C cells can also be induced by suramin, heparin, and other polyanions.
      As these compounds bind certain peptide growth factors, we assume that
      differentiation of BA-Han-1C cells is blocked by pathways involving autocrine or
      paracrine acting growth stimulating peptides. We present evidence that bFGF and
      cAMP inhibit induced differentiation in BA-Han-1C cells similar to normal
      myogenic cell lines, suggesting that signaling pathways mediated by these
      compounds are unaltered.

PMID- 8293038
TI  - Isolation of chicken phosphotyrosyl phosphatase cDNA sequences and identification
      of a brain-specific species related to human PTP zeta.
AB  - The first example of a chicken cDNA sequence encoding a phosphotyrosyl
      phosphatase (PTPase) has been identified and found to contain coding sequences
      for the entire cytoplasmic and membrane spanning domains as well as a portion of
      the extracellular region of a transmembrane PTPase resembling human PTP zeta.
      Like HPTP zeta, chicken PTP zeta contained two phosphatase domains (D1 and D2),
      and D2 lacked a critical cysteine residue required for catalytic activity. The
      entire intracellular portion of CPTP zeta was expressed in bacteria and shown to
      be capable of dephosphorylating both p-nitrophenylphosphate and reduced
      carboxyamidomethylated and maleyated lysozyme but not phosphoseryl casein.
      Genetic analysis indicated that the presence of D2 was required for full
      activity. CPTP zeta mRNA was identified as a single large transcript expressed
      exclusively in the brain of chick embryos at both early and late stages of
      embryogenesis. These results suggested that CPTP zeta may perform a brain
      specific function and have a role in development.

PMID- 8293039
TI  - Regulation of Na,K-ATPase beta 1 mRNA content by thyroid hormone in neonatal rat
      cardiac myocytes.
AB  - Incubation of primary cultures of neonatal rat cardiac myocytes in the presence
      of 100 nM triiodothyronine (T3) resulted in a three- to fivefold increase in the
      content of Na,K-ATPase beta 1 subunit mRNA which was maximal at 1 d of exposure
      to hormone. To investigate the mechanism by which T3 stimulates the abundance of
      beta 1 mRNA, transient transfection experiments were conducted with a chimeric
      gene containing a portion of the 5' end of the rat beta 1 gene linked to a
      luciferase reporter gene. We found no effect of T3 on chimeric gene activity
      either in the absence or presence of cotransfected T3 receptor. The effect of T3
      on the transcription rate of the endogenous beta 1 gene was quantitated by the
      nuclear run-on assay. T3 had no effect on beta 1 gene transcription following
      either 1 or 3 d of exposure and yielded a 1.3-fold increase at 6 d. These data
      indicate that T3 induction of Na,K-ATPase beta 1 mRNA content in neonatal rat
      cardiac myocytes in vitro is primarily mediated at a post-transcriptional site.

PMID- 8293040
TI  - Cyclosporine A enhances agonist-induced aggregation of human platelets by
      stimulating protein phosphorylation.
AB  - Use of the immunosuppressant drug cyclosporine A (CSA) has resulted in improved
      renal graft survival. However, an increased incidence of arterial and venous
      thrombotic diseases, hemolytic-uremic type syndrome, and findings resembling
      vasculitis in the kidneys of patients with CSA nephrotoxicity and accelerated
      atherogenesis have been reported. These disorders may be related to CSA-induced
      abnormalities in platelet function. We report here that CSA causes increased ADP
      stimulated aggregation in isolated platelet suspensions indicating that CSA has a
      direct effect on platelet function, independent of CSA interactions with plasma
      factors. Maximal hyperaggregability of ADP-stimulated platelets occurred
      following a 1 h preincubation period with CSA. Hyperaggregability of platelets
      due to the presence of CSA was dose-dependent and approached plateau between 200
      500 ng/ml CSA. We determined that CSA exerted its effects through a signal
      transduction pathway involving the phosphorylation of two intracellular proteins,
      a 40 kD substrate of PKC (p47) and the 20 kD light chain of myosin (p20), a
      substrate of calcium/calmodulin dependent kinase. Preincubation with CSA resulted
      in a 200% increase in the phosphorylation of these proteins in platelets
      stimulated with ADP. We conclude that CSA enhances ADP-induced platelet
      aggregation and secretion, in part, by potentiating the phosphorylative response
      of specific intracellular proteins to stimulation by agonists. This process may
      be responsible for the increased thrombosis and atherogenesis observed in CSA
      treated patients.

PMID- 8293041
TI  - Effect of okadaic acid on hepatocyte structure and function.
AB  - The aim of this study with rat hepatocytes was to describe the effect of okadaic
      acid (OKA) (a potent and specific inhibitor of protein phosphatases) on the
      biosynthesis, processing and/or secretion of various lipid and protein molecules.
      Gel radioautograms indicated that low concentrations of okadaic acid (100 nM)
      induced hyperphosphorylation of a number of hepatocyte phosphoserine/threonine
      residues in the Mr range of 35-220 kDa. The effects of okadaic acid on the
      morphology of the hepatocytes was time and dose-dependent; early changes included
      cell rounding, loss of typical Golgi staining of beta COP, and fragmentation of
      the Golgi compartment at the EM level. General hepatocyte cell functions such as
      protein synthesis, lactate dehydrogenase activity, and ATP levels were unchanged
      with 100 nM okadaic acid as were all hepatocyte functions carried out in the
      endoplasmic reticulum of these cells. As such, incubation with okadaic acid did
      not alter the biosynthesis of phosphatidylcholine (from labeled choline), or very
      low density lipoproteins (VLDL) from labeled fatty acids or glycerol. Likewise,
      the biosynthesis of various endoplasmic reticulum synthesized proteins
      (transferrin, albumin, apolipoprotein E, and HMG CoA Reductase) continued
      normally in the presence of okadaic acid. However, incubation with okadaic acid
      led to major changes in all hepatocyte functions normally carried out in the
      Golgi compartment; i.e., the incorporation of labeled ceramide into sphingomyelin
      was profoundly reduced, as was the Golgi-required packaging and secretion of
      various proteins synthesized in the endoplasmic reticulum. These findings point
      to the Golgi compartment as an specific target for okadaic acid and suggest that
      one or more okadaic acid-sensitive phosphoproteins may be involved in maintaining
      its normal structure and function.

PMID- 8293043
TI  - Bibliography of cellular and molecular biology research.

PMID- 8293042
TI  - SV40 DNA extracted from persistently infected Vero cells using miniprep columns
      for plasmids.
AB  - A recombinant pAT153 plasmid carrying the whole simian virus 40 (SV40) genome in
      the form of two consecutive Pst I restriction fragments was rapidly isolated
      using a commercially available minipreps DNA purification system. This rapid and
      simple method was used to extract SV40 DNA from infected Vero monkey cells. Viral
      DNA replication in persistently infected SVP-1 monkey cells was also conveniently
      followed over a period of 8 d by agarose gel electrophoresis and molecular
      hybridization using minipreps and the recombinant plasmid (pLCB104) as a probe.
      Unsatisfactory results were obtained, however, when herpes simplex virus DNA was
      tentatively extracted from infected Vero cells with the above method. Only
      covalently closed circular DNA molecules, with two strands unable to separate
      fully under denaturing conditions, were apparently retained after rapid
      neutralization by the silicone-based minipreps DNA purification resin.

PMID- 8293044
TI  - Can prevention lower health costs by reducing demand? No.

PMID- 8293045
TI  - Can prevention lower health costs by reducing demand? Yes.

PMID- 8293046
TI  - Study: auto insurance and health care reform could prove to be costly partners.

PMID- 8293047
TI  - Survey tracks chief roles of hospital board chairmen.

PMID- 8293048
TI  - Human resources ... top benefits officers say their companies will take
      aggressive action to rein in health care costs.

PMID- 8293049
TI  - Reengineering health care. A new management tool aims to transform the
      organizational processes--and stir discussion.
AB  - Looking for improved clinical quality, reduced costs, streamlined operations?
      Advocates of business process reengineering say it can help achieve all those
      things. But what is reengineering in a health care context? Experts look at the
      conceptual, operational and information management challenges.

PMID- 8293050
TI  - Interview with John Page. Interview by Mark Hagland.

PMID- 8293051
TI  - The big question. Will high levels of uncompensated care make some providers
      unattractive to emerging networks?

PMID- 8293052
TI  - Looming deregulation ignites networking efforts in New Jersey.

PMID- 8293053
TI  - Bringing providers to the people. Alaska and a Florida county blaze new trails in
      non-physician care delivery.

PMID- 8293054
TI  - Phoenix. Capitation becomes the driver aligning hospitals, physicians.

PMID- 8293055
TI  - Data watch. AHA survey shows continued shift to outpatient care.

PMID- 8293056
TI  - Providers beware: managed care contracts can be tricky.

PMID- 8293057
TI  - Low rates of return have hospitals searching for new investment.

PMID- 8293058
TI  - Old imaging technology gets renewed attention.

PMID- 8293059
TI  - Right moves: using a life cycle matrix when selecting physicians.

PMID- 8293060
TI  - Children's needs: a health care reform priority.

PMID- 8293061
TI  - Voice research: so what? A clearer view of voice production, 25 years of
      progress; the speaking voice.
AB  - The past 25 years has yielded an impressive growth in our knowledge of vocal
      function. Interdisciplinary research cooperation in areas of laryngeal histology,
      vocal aerodynamics and acoustics, vocal fold vibratory characteristics,
      neurolaryngology, and phonatory models has led to a clearer view of voice
      production. This article offers a brief review of the progress that has been made
      in our understanding of the speaking voice and relates this knowledge to clinical
      practice. The importance of utilizing voice research to confirm traditional
      management techniques and to develop new physiologically based management
      approaches is also stressed.

PMID- 8293062
TI  - Comparisons of pharynx, source, formant, and pressure characteristics in operatic
      and musical theatre singing.
AB  - Belting, a vocal technique typically cultivated in musical theatre singing,
      differs timbrally from operatic singing in many interesting respects. The
      underlying phonatory differences have not been previously investigated in detail.
      Yet, belting is frequently associated with disturbances of voice function.
      Articulatory and phonatory characteristics are investigated in a female subject
      who is a professional singer (co-author JL) trained in both the operatic and
      belting styles and in an intermediate vocal technique ("mixed"). This article
      presents data obtained from this subject by video-fiberoptic observation of the
      pharynx, inverse filtering of airflow, and measurement of subglottal pressure.
      The results reveal that belting was characterized by very high subglottal
      pressures and sound levels, and apparently also by a comparatively high degree of
      glottal adduction. Comparisons with other investigations of related aspects of
      belting and operatic singing support the assumption that the data obtained from
      our subject are representative for these vocal techniques.

PMID- 8293063
TI  - Infraglottic aspect of canine vocal fold vibration: effect of increase of mean
      airflow rate and lengthening of vocal fold.
AB  - The mucosal upheaval (MU), where the mucosal wave starts and propagates upward,
      appears only when the vocal fold vibrates. The location of the MU histologically
      and the effect of changes in mean air flow rate (MFR) and vocal fold length on
      occurrence of the MU were studied in twelve excised canine larynges. The lower
      surface of the vocal fold was marked to serve as a landmark for subsequent study.
      Cricothyroid approximation was performed to lengthen the vocal fold. After taking
      high-speed pictures or recording stroboscopic images from the tracheal side, a
      small cut wound was made at the mark. This wound served to compare the position
      of the MU with the histologically identified location of the mark. The larynx was
      then sectioned in the frontal plane. Before lengthening the vocal fold, the MU
      occurred on the area where the lamina propria became thinner and where the
      muscular layer neared the epithelial layer. After lengthening the vocal fold, the
      MU actually shifted medially compared with its original position. The subglottic
      area surrounded by the bilateral MUs became longer and thinner. Whether or not
      complete glottal closure during a vibratory cycle was achieved did not alter
      these findings. In contrast, with a fixed vocal fold length the MU appeared more
      laterally as MFR increased, but, based on the relation with the mark, its
      location on the vocal fold did not change from its original position before
      increase of MFR.

PMID- 8293064
TI  - The accent method of voice therapy: effect of accentuations on FO, SPL, and
      airflow.
AB  - The effect of the increased flow rate (delta U) in response to the Accent Method
      exercises on fundamental frequency (FO) and sound pressure level (SPL) was
      studied in three subjects (professionally trained, trained, and untrained in this
      method). In all the subjects, the rhythmic accentuated exercises produced a
      variable degree of increase in FO (delta FO) and SPL (delta SPL). The
      professionally trained subject showed greater delta FO and delta SPL in response
      to the delta U in the fastest tempo, which requires higher skills. Both trained
      subjects showed a greater correlation between delta U and both delta SPL and
      delta FO, as well as between delta FO and delta SPL, as compared to the untrained
      subject. The effects of the accentuated exercises on FO and SPL in response to
      the increased airflow rate (delta U) thus appear to demonstrate the treating
      effectiveness of the Accent Method.

PMID- 8293065
TI  - Time-shift, trial, and gender effects on vocal perturbation measures.
AB  - Three jitter and three shimmer measures were examined for: (1) the stability of
      the measured values with respect to shifts in sample site (starting point of
      window in the token) and (2) the effects of trial and gender. The perturbation
      measures and their coefficients of variation for windows starting from five
      different but adjacent cycles showed a dependence on sample size. Their
      variability with regard to shifts in sample site decreased asymptotically with
      increasing size. The data suggested no statistically significant trial effect
      except for APQ and no statistically significant gender effect except for absolute
      jitter. It is speculated that relatively long smoothing windows for shimmer (such
      as the one used for APQ) would allow the effects of slow vocal modulations (e.g.,
      tremor) to accentuate, especially for lower pitch speakers.

PMID- 8293066
TI  - The effects of premenstrual syndrome (PMS) on the female singer.
AB  - A review of the medical literature concerning the psychological, physical, and
      vocal effects of premenstrual syndrome reveals a wide range of significant
      effects for the female singer and a larger number of proposed treatments. A
      survey was conducted to evaluate the frequency and severity of 67 general
      physical and psychological symptoms and 20 vocal symptoms experienced by 104
      female singers. The variables of age, menstrual history, voice type, and
      performing experience were examined. The average number of general symptoms was
      33 and the average number of vocal symptoms three. The most frequently reported
      general symptom was abdominal bloating, while the most frequently reported vocal
      symptom was difficulty in singing high notes. The subjects reported that symptoms
      occurred with moderate regularity and severity. At age 35 symptoms decreased in
      number and severity.

PMID- 8293067
TI  - Consistency in clinicians' and clients' behavior in voice therapy: an exploratory
      study.
AB  - The primary purpose of this study was to investigate consistency in clinicians'
      behaviors during two voice therapy sessions. The secondary purpose was to examine
      relationships between ratings of clinicians' and clients' behaviors. Each
      clinician (n = 7) was observed working with two different clients. Two
      experienced evaluators, using the Adjective Checklist and five-point semantic
      differential scales, rated clinicians and clients. Results indicated that 6 of 10
      aspects of therapy studied were found to be relatively inconsistent, with the
      pace of therapy being the least stable. Ratings of individual clinician traits
      (e.g., favorable, unfavorable, intraception) were the most stable.

PMID- 8293068
TI  - Effects of vagal nerve stimulation on laryngeal function.
AB  - Functional electrical stimulation is a developing methodology that shows
      significant potential in the management of peripheral neuromuscular deficits.
      Potential applications in the head and neck area, including control of bilateral
      vocal fold paralysis and spasmodic dysphonia, have recently been explored.
      Despite promising early results, very little is known about the mechanisms of
      action or the long-term effects of electrical stimulation on human laryngeal
      function. Recent development of implantable vagal nerve stimulators as a method
      to control intractable seizures in individuals who have not responded to
      medication provides a unique opportunity to study its effect on the normal human
      larynx. Laryngeal and vocal function testing was studied on five individuals who
      had undergone vagal nerve stimulator implants for intractable seizures.
      Consistent abduction/adduction of the left vocal fold was achieved at 20 and 40
      Hz, respectively. Higher levels of electrical stimulation produced hemispasm of
      the larynx. Results were consistent with studies in the literature of recurrent
      laryngeal nerve stimulation in animal and human models. The vagus nerve provides
      relatively easy access for implantation of electrodes to provide electrical
      stimulation to the muscles of the larynx. Vagal nerve stimulation may prove
      efficacious in the treatment of movement disorders of the larynx; further study
      is needed.

PMID- 8293069
TI  - Treatment of sulcus vocalis: auditory perceptual and acoustical analysis of the
      slicing mucosa surgical technique.
AB  - Sulcus vocalis is a furrow in the mucosa of the vocal folds that causes glottic
      insufficiency, irregular vibrations, and a distinctive dysphonia of variable
      severity. Treatment of sulcus vocalis needs to achieve anatomical and functional
      improvements that satisfy the behavior of the larynx and vocal quality. We
      suggest a combined approach, which includes vocal fold mucosal surgery through a
      technique called slicing mucosa, followed by intensive vocal rehabilitation. The
      aim of the surgery is to detach the mucosa of the sulcus and to interrupt the
      longitudinal fibrotic tension lines. The results of this procedure in 10 patients
      were analyzed through visual, auditory, and acoustical methods, and the data lead
      us to conclude that the treatment proposed offered a good anatomical result, a
      better vibratory pattern, and an improvement in overall vocal quality.

PMID- 8293070
TI  - The Revised Australian Fiberscopic Profile.
AB  - The Australian Fiberscopic Profile (AFP) was developed for use in a previous
      study of normal voices to provide standard documentation for examining the larynx
      under continuous light. The AFP is being used currently in five specialized voice
      clinics in Australia to collect data on dysphonic voices. After use with 40
      clients it became obvious that a revision with clearer definitions of the
      parameters was needed to make it a more useful clinical tool.

PMID- 8293071
TI  - Characteristics of normal larynges under flexible fiberscopic and stroboscopic
      examination: an Australian perspective.
AB  - The purpose of this study was to investigate the structure and function of
      larynges of 35 subjects with normal voices. Volunteers aged between 20 and 50
      years with no history of voice disorders or laryngeal surgery, no current
      allergies, no formal voice training, and no hyperactive gag reflex were required
      to perform various vocal manoeuvres that were carried out under continuous and
      stroboscopic light. An assessment form was devised to record the condition and
      function of the larynx. The videotapes of the procedure were rated by experienced
      judges. The Australian Fiberscopic Profile was devised to record the relevant
      parameters under continuous light. Videostroboscopic ratings were carried out
      using the Bless protocol rating. High interjudge agreement was found across the
      two rating profiles.

PMID- 8293072
TI  - Structure of the channel catfish (Ictalurus punctatus) growth hormone gene and
      its evolutionary implications.
AB  - A DNA fragment of 1.6 kilo base pairs (kb), encoding part of the channel catfish
      (Ictalurus punctatus) growth hormone (GH) gene, was generated by the polymerase
      chain reaction (PCR) using 2 degenerate synthetic oligonucleotides (30 and 33
      mer) derived from the N- and C-terminal amino acid sequences of the catfish GH
      polypeptide as amplification primers and with catfish genomic DNA as a template.
      This DNA fragment was used as a probe for the isolation of a catfish GH gene from
      a genomic library constructed in a lambda phage cloning vector, lambda Dash II.
      Three positive clones were isolated, and their complete nucleotide sequences were
      determined. Nucleotide sequences from clones 1 and 3 were identical, whereas
      clone 2 had 2 base substitutions. The gene spans approximately 3 kb and is
      comprised of 5 exons and 4 introns. The initiation codon, the termination codon,
      and the canonical polyadenylation sequence were identified. The amino acid
      sequence deduced from the predicted coding region of the gene is in agreement
      with that of the native GH polypeptide sequence. A sequence (TATAAAA) matching
      the TATA box consensus sequence was located at nucleotide positions -30 to -23.
      Furthermore, 2 sequences corresponding to the mammalian Pit-1/GHF-1 binding sites
      (consensus sequence TT[AA]TATNCAT) were identified in the 5' flanking region
      starting at positions -113 and -134. Another sequence (GTACCAGTGA) conserved
      among the GH genes of the channel catfish and other known animal species was also
      identified at position -220. The biological functions of this sequence remain to
      be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293073
TI  - Detection and identification of a pathogenic marine Mycobacterium from the
      European seabass Dicentrarchus labrax using polymerase chain reaction and direct
      sequencing of 16S rDNA sequences.
AB  - Mycobacteriosis has become a major concern for the commercial mariculture of the
      European sea bass Dicentrachus labrax in Israel. The disease remains asymptomatic
      for a long time, is virtually impossible to eradicate with antibiotics, stunts
      the growth of the fish and renders the fish unmarketable. The pathogen was
      identified as Mycobacterium marinum by direct sequencing and analysis of
      approximately 600 bp of the pathogen ribosomal encoding DNA (rDNA). The
      polymerase chain reaction technique was evaluated as a diagnostic tool for
      detecting the infection in D. labrax and found to be highly specific and
      sensitive.

PMID- 8293074
TI  - Cloning and characterization of Atlantic salmon (Salmo salar) serum transferrin
      cDNA.
AB  - Characterization of Atlantic salmon serum transferrin cDNA representing a near
      full-length transferrin mRNA revealed a 2,070-bp open reading frame encoding a
      protein of 690 amino acids. The predicted protein contains an 18 amino acids'
      long signal sequence and shows 49% amino acid positional identity with Xenopus
      laevis transferrin and human serum transferrin. On the basis of sequence
      differences obtained from different salmon transferrin cDNA clones, 2 distinct
      classes of transferrin mRNA were identified. Both variants were present together
      in genomic DNA from haploid embryos, demonstrating that Atlantic salmon have 2
      transferrin genes per haploid complement. Salmon transferrin is expressed mainly
      in the liver.

PMID- 8293076
TI  - The origins of some of my conjectures concerning schizophrenia.

PMID- 8293075
TI  - Characterization of two full-length cDNA sequences encoding for apoproteins of
      peridinin-chlorophyll a-protein (PCP) complexes.
AB  - Characterizations are presented for RNA, 2 cDNA libraries, and 2 full-length cDNA
      sequences encoding for photosynthetic light-harvesting peridinin-chlorophyll a
      protein (PCP) in the dinoflagellate Heterocapsa pygmaea. Subsequent analyses of
      the PCP system also indicate that (1) it is represented by multiple nuclear
      encoded genes, (2) a subset of mRNAs encoding for PCP apoproteins are regulated
      by growth irradiance, (3) PCP preproteins are larger than the mature apoproteins,
      and (4) PCP cDNA clones sequenced thus far contain a conserved region but are not
      identical. Results are discussed in the context of photoadaptation in
      dinoflagellates.

PMID- 8293077
TI  - A strategy for elucidating genetic influences on complex psychopathological
      syndromes (with special reference to ocular motor functioning and schizophrenia).

PMID- 8293078
TI  - Issues in the validation of the personality disorders.

PMID- 8293079
TI  - Assessment of normal personality traits in a psychiatric sample: dimensions and
      categories.

PMID- 8293080
TI  - Emotion and psychopathology: a startle probe analysis.

PMID- 8293081
TI  - The genetics of affective disorders.

PMID- 8293082
TI  - DSM-III-R dysthymia: antecedents and underlying assumptions.

PMID- 8293083
TI  - Anxiety and the processing of emotional information.

PMID- 8293084
TI  - Explorations in schizotypy and the psychometric high-risk paradigm.
AB  - This chapter has presented a brief history of clinical and research interest in
      schizotypic psychopathology. Specific attention was focused on the theoretical
      model of schizotypy proposed by Meehl (1962, 1990), and the research implications
      of his model were discussed. Current (i.e., post-1980) schizotypy assessment
      methods were highlighted for consideration by those investigators who might
      conceptualize future research in schizotypy. A brief overview of the psychometric
      high-risk approach to schizotypy detection and current research conducted by the
      present author was discussed. Finally, a variety of methodologic issues that
      should be considered in the design and execution of future schizotypy research
      were surveyed and specific recommendations were made.

PMID- 8293085
TI  - [Calculation of gaseous forms and sizes of aerosol particles 131 Iodine- the
      radioactive fallout of Chernobyl accident by calculation of inhaled radiation
      dose].
AB  - After the Chernobyl accident the isotopes of radioiodine in air were detected
      both in aerosol and gaseous forms. In the ICRP publication, No 30 the committed
      dose equivalent in thyroid per intake of unit activity of 131I, B(ih), were
      presented. This value holds true only for aerosols with activity median
      aerodynamic diameter (AMAD) 1 micron. The radioactivity deposition coefficients
      in human respiratory tract have another values for molecular and organic forms of
      gaseous radioiodine. In present work the measured AMAD and the proportion between
      aerosols, molecular and organic forms of 131I in various regions after the
      accident are given. The correction factors for B(ih) are calculated for the
      following cases: 1) the radioiodine concentration in air is measured by means of
      the aerosol filter only, 2) all forms of radioiodine are sampled. The neglection
      of the gaseous forms of radioiodine could lead to extremely large errors in the
      determination of inhaled dose radiation: the real value of dose radiation could
      exceed calculated one by more than 5 times.

PMID- 8293086
TI  - [Development of toxemia in rats with long-term irradiation].
AB  - Prolonged whole-body gamma-irradiation of rats by daily dose 0.5 Gy up to total
      dose 8 Gy led to excessive bacterial intoxication with simultaneous decrease of
      the number of leucocytes and their migration rate. Additional thermal burn of
      exposed rats resulted in more strong bacterial intoxication, increase of the
      number of toxic oligopeptides and decrease of leucocytes migration rate. Isolated
      thermal lesion caused short-term and less pronounced increase of indices under
      study.

PMID- 8293087
TI  - [Effect of single-dose external gamma-irradiation of 0.5 g on the development of
      rat's embryos].
AB  - Primigravida 4-month rats were exposed to single whole-body external gamma
      radiation (137Cs, 0.5 Gy) during organogenesis on days 9 and 15 of pregnancy. The
      embryotoxic effect of radiation was studied on the 20th day of pregnancy. The
      irradiation caused significant growth disorders characterized mainly by a
      nonuniform hypoplasia of fetus organs. This effect was most pronounced in fetuses
      irradiated on the 15th day of the intrauterine development.

PMID- 8293088
TI  - [Evaluation of energetic status of the rat's brain in acute gamma- irradiation of
      various doses by the results of 31 R-NMR in vivo study].
AB  - Changes in relative concentrations of brain phosphates participating in energy
      metabolism and intracellular pH at selected time intervals after whole body gamma
      irradiation at a single dose of 6.5 or 300 Gy were studied by 37P NMR in vivo.
      The decrease in correlations between measured parameters under acute radiation
      exposure was demonstrated.

PMID- 8293089
TI  - [Mechanisms of induction of congenital disorders of the nervous system and immune
      reactivity in newborns with irradiation and other factors in utero. Theoretical
      analysis].
AB  - Proposed is a mechanism through which exposure in utero to deleterious agents
      (including radiation) induces hereditary nervous (and immune) deficiencies in
      newborns. This mechanism was found theoretically in the framework of
      multidisciplinary analysis of neuroimmunoendocrine reactivity development
      peculiar to normal embryogenesis in comparison to that under in utero exposure.
      Found systemic mechanism accounts induced neural (and or) immune reactivity
      deficiencies on the response of embryonic homeostasis to effects of radiation or
      any other deleterious agent on growth potencies of embryo cells. Paradoxically,
      in the frame of the theory, this homeostatic response appears adverse to normal
      development of nervous (and immune) reactivity of a newborn after in utero
      exposure. Therefore, well known phenomenon of "overall" susceptibility of nervous
      and immune reactivity of a newborn to in utero action of a vast majority of
      harmful agents has met its first elucidation. Proposed theory of a "systemic
      teratogenesis" is in accordance with known specific endocrine grounds of nervous
      diseases. It also prognosticates the existence of systemic effects on nervous and
      immune reactivity resulting from radiation exposure at preimplantation stage of
      embryogenesis. Such effects were never observed before. Thus, the theoretically
      founded mechanism appears quite verifiable in the frame of proper animal
      experiments.

PMID- 8293090
TI  - [Effect of supposed radioprotectors on oxidation-reduction of vitamin E in the
      tissues of irradiated rats].
AB  - In experiments with mature Wistar male rats under irradiation by dose of 5 Gy the
      effect of emoxypine, citomedine and echinacea purpurea on the content of
      liposoluble vitamin A, carotene, vitamin E and its metabolites (quinone and
      oxidized tocopherol) in blood plasma, spleen, liver and testes was studied. It
      was shown the drugs under study mobilized the internal reserves of these vitamins
      and promoted effective functioning of vitamin E redox system. Mechanisms of their
      action are different. The drugs might be used as radioprotectors, but they
      exhaust the reserves of the liposoluble vitamins. Therefore they should be used
      in a combination with vitamin preparations.

PMID- 8293091
TI  - [Effect of riboxine on mice resistance to long-term gamma-irradiation in non
      lethal dose].
AB  - In experiments with mice subjected to long-term irradiation with a non-lethal
      dose of 4 Gy, (0.017 Gy/min), it has been shown that the number of chromosome
      aberrations in myelocaryocytes is reduced, the cell precursors pool in the bone
      marrow and the germinative epithelium are unchanged, the number of lipid
      radiotoxins decreases, and cell membranes are stabilized after a single dose of a
      purine nucleoside, riboxine (150 mg/kg, 12 h prior to irradiation).

PMID- 8293092
TI  - [New mechanisms of antimutagenic effect of interferon].
AB  - A study was made of the antimutagenic effect of natural lymphoblastoid interferon
      and alpha 2-recombinant interferon against initial damages to DNA induced by 8
      methoxypsoralen, activated by UV-light, in human peripheral blood. The
      crosslinking and uncrosslinking 8-methoxypsoralen monoadducts were shown to make
      different contribution to the biological effects in cells, that is, chromosome
      aberrations and sister chromatid exchanges. Both of the investigated interferons
      exhibited their protective effect with respect to crosslinking monoadducts only.
      The antimutagenic action of interferon was implemented by a non-repair way. It is
      suggested that the scavenging of active radicals is a possible mechanism of the
      protective action of interferon.

PMID- 8293093
TI  - [Effect of slow action calcium channel inhibitors on the radioprotective effect
      of mezaton ].
AB  - Verapamil and cinnarizine decrease radioprotective effect of phenylephrine, but
      nifedipin (more specific inhibitor of slow calcium channel) doesn't change it.
      Consequently, protective effect of phenylephrine isn't realized by influx of Ca2+
      ions through slow calcium channel.

PMID- 8293094
TI  - [Post-irradiation changes of metabolic and functional activity of adhesive
      macrophages].
AB  - Research into dose- and time-dependent alterations of quantitative and
      qualitative composition of the peritoneal cells has been carried out. Exposure at
      3, 5, 7, or 9 Gy reduced the total number of peritoneal cells, increased the
      activity of the lactate-, malate-, and qlucoso-6-phosphate dehydrogenases, of the
      acid phosphatase and catepsin D; the amount of the cell protein in adhesing
      macrophages was also increased. The exposed macrophages showed enhanced
      phagocytic and cytotoxic activity as evidenced by the increase in luminol- and
      lucigenin-enhanced chemilumenscence in vitro. The most pronounced changes took
      place 7-9 days after exposure at 9 Gy.

PMID- 8293095
TI  - [Hemostasis in hens with exposure to low-dose gamma-irradiation in the embryonal
      period].
AB  - Exposure of hen's eggs to irradiation by doses 0.05-1.66 Gy (dose rate 2.56x10-4
      Gy/s) in early embryonal period (1st day of incubation of eggs doesn't
      essentially affect on indices of functional state of haemostasis system of two
      month aged individuals, except the activation of contact phase of blood
      coagulation, in which a hypercoagulation shift within normal fluctuations has
      been noted.

PMID- 8293096
TI  - [Structure of low-molecular DNA in the blood plasma of irradiated rats].
AB  - Low-molecular DNA in blood plasma of rats appeared after gamma-irradiation in a
      dose 8-100 Gy. This DNA has been cloned and the 26 clones have been sequenced.
      The search for sequence similarity between the designated sequences and sequences
      in EMBL allowed the three homology to LINE 3 sequences to be found. The
      differences in the structure of low-molecular DNAs extracted from rat blood
      plasma after irradiation of rats in doses 8 and 100 Gy were not found.

PMID- 8293097
TI  - [Immune reaction in monkeys to single and fractionated low-dose gamma
      irradiation].
AB  - A study was made of total and local immunity of two groups of Papio hamadryads
      subjected to single and ten-fold external gamma-irradiation at a cumulative dose
      of 5 cGy. It has been shown that with equal dosages changes in the relative and
      absolute number of lymphocytes in the peripheral blood, the number of circulating
      T-cells and their functional activity are more pronounced in animals subjected to
      fractionated irradiation. Both groups exhibited similar disturbances in the
      functional activity of antibody-dependent killers and in local immunity of
      stomatopharynx. Analysis of the immunological data and the results of
      hydrocortisone content determinations in blood serum of exposed animals has
      demonstrated the presence of both direct effect of low-level radiation on the
      immune system and indirect effect that is particularly pronounced in case of
      multifraction long-term irradiation.

PMID- 8293098
TI  - [Role of DNA double strand breaks in the radiation structural mutagenesis in
      eukaryotic cells].
AB  - The latest experimental findings in the field of radiation-induced structural
      mutagenesis especially concerned with the role of the DNA double strand breaks
      (DSBs) in the formation of chromosome aberrations were analyzed. It was shown
      slow-repairable and non-repairable DSBs appeared to be the DNA critical damages
      leading to aberrations.

PMID- 8293099
TI  - [Microwaves and blood-brain barrier].
AB  - It is presented the analytical review of the effect of radiofrequency and
      microwave radiation on function on blood-brain barrier (BBB) in experimental
      animals. Analysis of referenced papers encompasses the issue of the relation of
      BBB changes on the power and temporal parameters, regimens of generation of
      acting radiation and its unevenness. Along with this the authors tried to
      generalize the cited works considering the marker, used in BBB studies, its
      molecular mass, to present the sensitivity of isolated brain structures under
      influence of microwaves to the permeability of several substances, their
      dependence on thermogeneity of acting levels as well as to draw attention to
      reversibility of detected changes.

PMID- 8293100
TI  - [Radiation hormesis, radiation stimulation or hyperfunctional effect of ionizing
      radiation?].
AB  - The term "radiation hormesis" is thought of unsatisfactory one because it is
      difficult to define such concepts as "benefit", "harm" or "contributory" with
      respect to irradiation of biological species. The term does not take into account
      a fact that large doses stimulate the same biological processes and functions as
      low ones. The definition of the effect of radiation stimulation as physiological
      hyperfunction response of biological object to ionising radiation is proposed.

PMID- 8293101
TI  - [Disorders of spermatogenesis in people working at the clean-up of the Chernobyl
      nuclear power plant accident].
AB  - It has been studied the state of ejaculate of 125 men, participated in
      liquidation of Chernobyl disaster consequences in 1986-1986 and irradiated by
      doses up to 25 rem. For all checked men the decrease of ejaculate volume and the
      number of spermatozoa with increasing of part of immovable and degenerated forms
      has been found. Maximal changes have been observed for men being at Chernobyl NPS
      in 1986 and exposed by dose more than 10 rem. The majority of these persons have
      asthenooligospermia in 1st degree. The majority of men exposed by total dose more
      than 1 rem have teratozoospermia. Two men exposed by dose more than 10 rem suffer
      from azoospermia.

PMID- 8293103
TI  - [Radiation-induced changes of circadian dynamics in the behavioral reactions of
      rats in the "open field"].
AB  - The interaction of daily motor activity rythm within daily changes of early
      transient neurological disorders (ENTD) symptoms has been evaluated. The highest
      frequency of five ENTD symptoms was mainly observed in that daily periods when
      behavior reactions were minimal. A difference was distinguished in circadian
      radiosensitivity of some behavior reactions in "open field" (gamma-irradiation
      60Co, 62.5 Gy). The most radiosensitive ENTD symptoms were "vertical set",
      "immobility" and "motion on the spot", characterized emotional state and
      orienting-locomotor animal reactions. Certain changes of orto- and paraphases of
      these behavior reactions biorythms due to irradiation have been revealed.

PMID- 8293102
TI  - [Modification of Ca2+ metabolism in the blood cells of cattle with radiation
      induced thyroid disorder after the Chernobyl nuclear power plant accident].
AB  - Increasing of Ca2+ concentration in cytoplasm and of the rate of 45Ca iflux into
      cows erythrocytes in 19-24 month after Chernobyl accident was revealed.
      Correlation between Ca2+ concentration in cytoplasm of erythrocytes and thyroxin
      content in plasma of cows with radioiodine damage of thyroid gland was found.
      Reduction of the rate of 45Ga influx into erythrocytes in cows with radiation
      doses of 20-60 By on thyroid gland was shown in later time after accident (3-5
      years). Changes in Ca2+ permeability through membranes of erythrocytes and
      neutrophils after injection of 131I into calves in doses of 300 Gy and more on
      thyroid gland was found.

PMID- 8293104
TI  - [Effect of Sr-90 on the reproductive function of rats after chronic exposure].
AB  - In experiments on white rats following long-term 90Sr exposure within a wide dose
      range the effect of 90Sr on reproductive function of animals has been observed
      both over the entire reproductive period and in seven subsequent generations. It
      has been established that the ovule fertilization and the intrauterine fetus
      development did not differ from these values in control animals. However in some
      cases the loss of progeny was significant following the isolation of animals from
      parents. The physical development of rats in suckling period and sex proportion
      did not differ from the control progeny.

PMID- 8293105
TI  - [Clinical and experimental investigation on the radioprotective effect of
      riboxine in low-dose fractionated irradiation].
AB  - In experiments with dogs (fractionated y-irradiation, accumulated dose 1Gy) as
      well as in clinical testing of the group of men, recieved 0,25 Gy being engaged
      in the Chernobyl NPS disaster repairment, the positive influence of riboxin
      (purine nucleoside) course treatment on parameters of peripheral blood and non
      specific resistance system has bee n shown.

PMID- 8293106
TI  - [Radioprotective effect of synthetic immunomodulators on hemopoietic CFU-S].
AB  - The radiotherapeutic effect of thymogen (Glu-Trp) and thymohexin (Arg-Lys-Asp-Val
      Tyr-Arg) synthetic peptide immunomodulators was investigated. Both thymogen and
      thymohexin were demonstrated to be able to reduce the damaging effect of ionizing
      radiation (1 Gy) on CFU-S by half. The treatment by these preparations after
      irradiation at dose of 4 Gy leads to more intensive restoration of CFU-S
      population as compared with control.

PMID- 8293107
TI  - [Adaptive response in vivo: reasons for increase of radioresistance in CFU-S].
AB  - The data concerning the reasons of CFU-S radioresistance increase after low dose
      irradiation of mice were obtained; the reparation processes in CFU-S adapted by
      low dose irradiation were shown to be more active than in intact ones. Colony
      formation increase was demonstrated to be more pronounced in adapted animals when
      they had been injected by 50 mcg of synthetic polyribonucleotide PolyI-PolyC two
      days before irradiation in challenge dose. The thymogen immunomodulator
      administration to adapted and intact donor animals leads to the increase of
      colony yield in equal extent.

PMID- 8293108
TI  - [Modifying effect of tributylphosphate (TBP) and hexachlorbutadien (HCLB) on non
      stochastic effects of inhaled Pu-239].
AB  - It has been established in experiments on rats that under combined inhalation
      exposure to 239Pu along with TBP and HCLB in amounts which may cause the changes
      in blood and immune systems the enhancing of different non-stochastic effects on
      the average by two times on a basis of a unit absorbed dose in comparison with
      isolated nuclide inhalation.

PMID- 8293109
TI  - [Correlation between structure and radioprotective activity (RPA) in thiazole
      derivatives].
AB  - The method of potential functions was used to predict adequately the
      radioprotective efficacy of thiazole derivative series, the geometrical indexes
      (1n A2 and A6) and anti-ion mass being applied as descriptors for organic and
      inorganic molecule parts respectively.

PMID- 8293110
TI  - [Radiation-modifying effect of hypoxia, and tissue basophils of skin in rats:
      possibility of individual prognosis].
AB  - In experiments on rats the data about relationship between individual properties
      of skin tissue basophil population and animal's radioresistance under total gamma
      irradiation (11 Gy) at severe hypoxia has been obtained. The method for
      estimation of state of tissue basophil population by means of reactivity index
      has been proposed. An opportunity for using of this index to predict some
      radiobiological patterns has been shown.

PMID- 8293111
TI  - [Extracellular DNA of blood after irradiation].
AB  - It has been shown that blood extracellular DNA of irradiated rats largely
      consists of the low-molecular DNA and its oligomers. Molecular masses of
      oligomers are multiple to molecular mass of monomer fragment with nucleosome
      size. The low-molecular DNA has linear form. The average content of GC-pairs in
      low-molecular DNA is higher than in total rat's DNA (48.5% against 41.5%). The
      low-molecular DNA is a part of complex containing RNA, acidic proteins and
      lipids. It is assumed that the formation of low-molecular DNA is a result of
      Ca/Mg-dependent nuclear endonuclease action.

PMID- 8293112
TI  - [Effect of colostrum polypeptide on structure and lipid peroxidation in liver
      nuclei of rats late after gamma-irradiation].
AB  - Rats were irradiated by 8Gr in a doze power of 2.33 R per second. A portion of
      animals were injected subcutaneously with a cow colostrum polypeptide (CP) in a
      doze of 1 mg per g of body weight before the irradiation and daily after the
      irradiation during 4 days. In irradiated rat liver nuclei injected with CP the
      lipid peroxide oxidation was restored. At 90th day after the irradiation the
      production of dienes and dieneketones in liver nuclei oscillated in normal
      limits. The structure and cytochrome-c-oxidase activity of the nuclei was
      restored to 60-90th day after the irradiation.

PMID- 8293113
TI  - [Comparative study of the effect of radiation and other lymphatic agents on
      lymphoid tissue of dogs and rats: chromatin degradation, DNA and protein
      synthesis in cells].
AB  - It is established that lymphatic tissue of dogs shows far less degradation of
      chromatin after whob body irradiation (6 Gy) or exposure to lympholytic agents
      (hydrocortisone and colchicine), compared to rats. The fragmentation of chromatin
      in dog thymus occurs, like in rat, according to the internucleosome type, but
      affects a considerably less part of the thymocyte population.

PMID- 8293114
TI  - [Stimulation of fibroblasts' growth in culture by low-dose ionizing radiation in
      acute irradiation].
AB  - The effect of low irradiation doses (10-100 cGy) on the growth of Chinese hamster
      fibroblasts was examined. It was shown that the number and the mean size of
      colonies increased after irradiation with doses of 10-40 cGy. Dependence of the
      effect on dose is extremal with maximum at 10-20 cGy. Irradiation by dose of 10
      cGy did not affect on the cell cycle duration but significantly shortened the las
      phase of growth.

PMID- 8293115
TI  - [Effect of chronic irradiation on cytogenetic mammalian cell injuries in
      culture].
AB  - The action of chronical irradiation on Chinese hamster fibroblasts and human
      peripheral blood lymphocytes was studied. The similar character of dose response
      for both types of cells and the absence of dose-rate effects at low doses were
      shown.

PMID- 8293116
TI  - [Aggregational thrombocyte activity in rats in post-radiation rehabilitation].
AB  - Platelet aggregation in rats was investigated after total gamma-irradiation with
      a dose of 2 Gr. At period postirradiation repair the phase character of changes
      of some aggregation parametres was discovered. After 2-6 months the main
      direction of age changes of aggregation activity was preserved, but
      disaggregation time was lesser then in control group.

PMID- 8293117
TI  - [Effect of chronic neutron irradiation on fibroblast cell culture in Chinese
      hamster].
AB  - The effect of monoenergy (30 Gev) neutron radiation on Chinese hamster
      fibroblasts has been studied by micronuclear test. It has been shown that in the
      range of doses up to 60 cGy RBE is equal to unity.

PMID- 8293118
TI  - [Maximum permissible level of disseminated laser radiation with the wave length
      of 0.44 mkm].
AB  - There where investigated the local and general reactions of 48 male rabbits
      (chinchilla) exposed to diffused laser radiation with wavelength of 0.44 microns.
      In the experiments 120 days period of exposure followed by 30 days period of
      rest. The maximal permissible level for laser radiation was established.

PMID- 8293119
TI  - [Maximal permissible level of disseminated laser radiation with the wave length
      of 0.44 mkm].
AB  - In experiments in male rabbits ("chinchilla") the parameters of single action of
      diffused laser radiation with wavelength of 0.44 microns were established by the
      method of reooftalmography. The value of maximal permissible level for the
      radiation under study was proposed.

PMID- 8293120
TI  - [Radiobiological characteristics of tritium labeled lysine].
AB  - Experiments on mice and rats injected with tritium-labeled lysine have revealed
      that one day after injection about 80% of the label was retained in organs and
      tissues as tissue-bound tritium. Retention curves for tritium in the body were
      decomposed into two exponentials. The biological half-lives of tritium-labeled
      lysine in various tissues exceed half-lives of other tritiated amino acids and of
      tritiated water. The average dose in different tissues following injection of
      tritiated lysine exceeds that from equal quantity of tritium oxide (THO) by 1,5-8
      times. Contribution of the tissue-bound tritium in dose is about 90%.
      Radiobiological experiments showed strong genetic and cytotoxic effects in male
      mice after injection of tritium-labeled lysine.

PMID- 8293121
TI  - [The multinucleate cells of the spermatogenic layer in rats as a criterion of
      hypoxic damage to the testis].
AB  - The formation and dynamics of transformations of multinucleated cells in the
      spermatogenic layer was studied in mature male albino rats in a model experiment
      with 10-12 min. long clinical death followed by revivification at different
      periods of the postreanimation period. The maximum formation of multinucleated
      cells is observed on the 2nd-3rd days after revivification, and further their
      occurrence becomes less. With an increase of degenerative alterations in the
      nuclei and cytoplasm of multinucleated cells, the latter become isolated from the
      spermatogenic layer causing disturbances of its structure. A variant with the
      multiple formation of multinucleated cells is described resulting in an injury of
      the spermatogenic layer at a considerable distance. A supposition is put forward
      of the relationship of the formation of multinucleated cells with the clonal
      syncytial principle of organization of the developing sex cells and the cycle of
      spermatogenesis. The appearance of multinucleated cells is an undoubtable
      indicator of degenerative alterations of the spermatogenic layer under conditions
      of hypoxia.

PMID- 8293122
TI  - [The ovarian histophysiology of the progeny in unilateral ovariectomy in rats].
AB  - The ovaries of rats which are progeny of females subjected to unilateral
      ovariectomy 1.5-2 months before mating were studied by methods of morphometry and
      histochemistry. The animals were divided into 3 age groups (5 days, 3.5-4 and 10
      months). Their ovaries were shown to differ from gonads of rats in control
      groups. The differences were concerned with the main parameters characteristic of
      female gonads: their mass, amount of follicles, intensity of their atresia.
      Possible mechanisms responsible for the differences in question are discussed.

PMID- 8293123
TI  - [The intergroup variability of the indices of asymmetry of the human facial
      skull].
AB  - All bilateral sizes of the facial skeleton of Tajik, Khakass and Kazakh skulls
      have demonstrated an asymmetry. In the three series the greatest values of the
      asymmetry were obtained for the sizes of the orbital, zygomatic and mandibular
      areas, the least ones--for the sizes of the upper jaw. Greater sizes were less
      asymmetrical. The indices of asymmetry of the least sizes of the facial skeleton
      are characterized by the greatest variability at the intra-group level. The Tajik
      skulls were considerably different in the degree of asymmetry from both the
      Khakass and kazakh skulls mainly in the sizes of the upper part of the facial
      skull. Values of asymmetry of Kazakh and Khakass skulls were similar as a whole.

PMID- 8293124
TI  - [A method for constructing a system of topographical coordinates of the human
      body].

PMID- 8293125
TI  - [Metabolic markers of neuronal activity].

PMID- 8293127
TI  - [An increase in student interest in lectures on human anatomy].

PMID- 8293126
TI  - [Debatable questions in the terminology of the structures of the heart and the
      conduction system].

PMID- 8293128
TI  - [The anomalous development of the nervous system of the human embryo at 3.2 mm of
      length].
AB  - Serial histological preparations of a human embryo of 3.2 mm parieto-coccygeal
      length were studied. The morphological organization of the embryo had a
      combination of signs typical for the 10, 11 and 12th stages of the human
      development. Neurulation in the abnormal embryos was completed at the stage of 6
      somites which is 2-3 days earlier than in a normally developing embryo. The
      embryo had no neural tube and the neuroepithelial cells represented a homogeneous
      cord without signs of striatal or nuclear organization. The embryo was found to
      have germs of the ocular vesicles, induced germs of the lens, olfactory and
      auditory placodes. Disturbances in the differentiation of the chordomesoderm and
      germs of branchial pockets took place. The changes observed are supposed to be a
      result of relaxation reactions of the neuroepithelium of the neural tube in
      response to nonspecific mechanico-chemical actions at the end of neurulation.

PMID- 8293129
TI  - [The morphometric characteristics of the nonpyramidal neurons in field CA1 of the
      human hippocampus].
AB  - The content of lipofuscin is different in pyramidal and nonpyramidal neurons
      (NpNH) of the pyramidal layer of the field CA1 of the brain hippocampus of adult
      man. This criterion allowed using the method of intracellular administration of
      Lucifer yellow for staining NpNH only. The morphometrical analysis of geometrical
      parameters and orientation of the dendrites allowed all the NpNH to be divided
      into 4 types: large multipolar spine-free neurons, middle-sized multipolar spine
      free neurons, middle-sized multipolar neurons with short dendrites and small
      bipolar reticular neurons.

PMID- 8293130
TI  - [Structural changes in the endothelium of the major arteries under conditions of
      longitudinal stretching in vivo (based on scanning electron microscopic data)].
AB  - The method of scanning electron microscopy was used for studying three
      dimensional organization of the endothelium of major vessels under conditions of
      distraction in vivo. The distraction resulted in an enlargement of the spaces
      between endotheliocytes without formation of considerable areas of
      deendothelialized surface. The main mechanism of induction of flattening and
      division of endotheliocytes in the zone of distraction seems to be the
      elimination of the contact inhibition resulting from a mechanical distraction.

PMID- 8293131
TI  - [The blood microcirculatory bed of the liver in fetuses under increased physical
      loading in pregnant rats].
AB  - Morphological and morphometrical methods were used to study the
      hemomicrocirculatory bed of fetuses during greater physical exercise of pregnant
      rats during 18 and 21 days. As a result, a mosaic picture is noted in the liver.
      There appear areas with sharply constricted vessels which alternate with dilated
      vessels and loci of hemorrhages of different sizes. In the areas of the liver
      with narrow vessels minimum dystrophic changes were noted. In areas with dilated
      vessels, particularly in the II and III zones of the acinus, there were
      pronounced dystrophic alterations of the walls of vessels and hepatocytes which
      is a manifestation of the organ hypoxia. Besides the dystrophic processes in the
      liver there appear symptoms of adaptation-compensation phenomena such as a
      greater amount of foci of hemopoiesis, elevated activity of redox enzymes, higher
      content of glycogen in hepatocytes by the 21st day. The increased physical
      exercise of the mother results in faster differentiation of the walls of the
      hemomicrocirculatory bed vessels (interlobular veins and arterioles, sinusoids,
      central and collecting veins) of the fetus liver, mainly in the portal vein
      system, and accelerated processes of the formation of its architectonics.

PMID- 8293132
TI  - [The formation of definitive variants in the organization of the rudimentary
      portion of the thoracic duct in the prenatal period of human ontogeny].
AB  - The aim of the investigation was to find out the anatomo-topographic parallels in
      the development of the initial part of the thoracic duct, organs of the abdominal
      cavity and branches of the abdominal aorta which takes place due to taxis of the
      physiological umbilical hernia and secondary adhesion of the peritoneum.
      Specificity of these processes determines variability of branching of the
      abdominal artery and the formation of the duodenum, the increasing pressure to
      the posterior wall of the abdomen and mesentery where the presumptive lymph
      collectors are found. The degree of their separation by invaginations of blood
      vessels, the rate and spread of the development of lymph nodes are responsible
      for the structure and position of the initial part of the thoracic duct in human
      fetuses. The results obtained may be taken as a morphogenetic ground for search
      of the local reference points for the initial part of the thoracic duct.

PMID- 8293133
TI  - [The possibility of the influence of the germ cells on their somatic
      environment].
AB  - The paper is devoted to actual problems of the intercellular regulatory relations
      in the male gonad of mammals. Literature data on this problem are analyzed as
      well as the results of the personal findings. The problem of the influence of sex
      cells on the somatic surroundings are analyzed from different standpoints.
      Grounds of the necessary accounting of data of the paracrine interrelations in
      the gonad are given for a principally new approaches to studying the
      histophysiology of this organ.

PMID- 8293134
TI  - [The localization of the regional ovarian lymph nodes in girls and mature women].
AB  - The method of interstitial injections followed by preparation was used to
      investigate the regional lymph nodes of the ovaries located in the
      retroperitoneal space in 18 preparations from corpses of women of different age.
      The permanently occurring (in all the cases) precaval lymph node, regional for
      the right ovary and permanent lateral aortal lymph node, regional for the left
      ovary were determined. The shape, syntopy, skeletotopy of these nodes are
      described. Their sizes are determined. It was established that the level of
      localization of both the precaval and lateral aortal lymph nodes displaced
      downward with age relative to the vertebral column. However, the level of
      localization of the permanent lateral aortal lymph node, regional for the left
      ovary is higher than the precaval lymph node regional for the right ovary
      irrespective of the age. The distance from the place of localization of permanent
      lymph nodes to the vertebral column axis increases with age. For example, the
      precaval lymph node in early childhood is at a distance of 9 +/- 0.4 mm (8-10
      mm), in the second period of childhood at a distance of 14 +/- 0.8 mm (13-15 mm),
      and at the first period of adult age at a distance of 24 +/- 2.9 mm (20-27 mm) to
      the right from the vertebral column axis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293135
TI  - [The histotopographical characteristics of the muscular structures of the wall of
      the human esophagus in the area of the bronchial constriction].
AB  - The zone of the bronchial constriction of the esophagus and the area of the upper
      and lower dilatation of the esophagus was studied in humans of different age by
      the morphohistotopographic method at the macro- and microscopic levels. The
      bronchial constriction area of the esophagus was found to have a thickening of
      the circular layer of the muscular tunic, less relative thickness of the
      longitudinal layer, changed course of muscular fibers. The smooth muscle
      thickening of the circulating layer of the muscular tunic is localized at the
      boundary of the transitional zone of the displacement of the striated muscle
      fibers by smooth myocytes. The above morphological signs are characteristic of
      the areas with sphincter functions which allows to consider the bronchial
      constriction as a sphincter zone of the esophagus.

PMID- 8293136
TI  - [The karyometric characteristics of rat lung tissue during prenatal development].
AB  - The embryonic histogenesis of tissues of mesenchymal and epithelial origin was
      studied in the lungs of 150 embryos of the Albino rat (from 10 to 21 days of
      development) by methods of morphometry. Two phases in the dynamics of the nucleus
      form factor were established. The first phase (10-14 days) coincides with
      processes of programming and determination of the cells and is completed by a
      separation of the muscular, connective and cartilaginous tissues from the common
      mesenchymal germ. The second phase (16-21 days) is characterized by the divergent
      development of mesenchymal derivatives and demonstrates processes of
      cytodifferentiation and specialization of the cells. The appearance of
      heterogeneity of the cell forms leads to a growth of entropy of tissue anlagen.
      The restriction of the entropy is achieved by the integration of structures
      resulting from the formation of the system of correlation connections. Their
      amount first grows, and when specialization begins it becomes less.

PMID- 8293137
TI  - [The ultrastructure of the main exocrinocytes in the glands proper of the gastric
      mucosa in A avitaminosis].
AB  - The electron microscopic and morphometrical methods were used to study the
      ultrastructural organization of main exocrinocytes of the proper glands of the
      mucous membrane of the stomach of rats under conditions of A-avitaminosis.
      Deficiency of vitamin A causes dystrophic alterations of main exocrinocytes. The
      fragmentation, degranulation and considerable dilatation of cisterns of the
      granular endoplasmic reticulum, destruction of the Golgi complex membranes,
      disturbance of the membranous organization of secretory vacuoles were observed. A
      conclusion is made of disturbances of the protein-synthesizing function of main
      exocrinocytes under conditions of A-avitaminosis.

PMID- 8293138
TI  - Immune-mediated neuropathies.
AB  - Identification of immune-mediated neuropathies is important as these disorders
      often respond to treatment. Patterns of binding of serum M (monoclonal) proteins
      and autoantibodies correlate with, and may be diagnostic markers for, specific
      polyneuropathy syndromes. There is evidence that some of these antibodies may
      play a pathogenic role in polyneuropathy syndromes. Identification of specific
      immune polyneuropathy syndromes provides guidance regarding immunosuppressive
      regimens that may be effective treatments.

PMID- 8293139
TI  - The muscular dystrophies and dystrophin.
AB  - Recent progress in molecular genetics has resulted in more insight in the
      molecular biology of muscles and the muscular dystrophies, and has provided more
      reliable tools for prenatal and presymptomatic diagnosis in several disorders.
      The state of research is reviewed with emphasis on genetic aspects.

PMID- 8293140
TI  - Toxic neuropathies and myopathies.
AB  - This review first considers toxic neuropathies of recent interest, including
      those caused by antineoplastic and antiretroviral drugs, agents that affect
      methylation reactions, vitamin and herbal preparations, and certain occupational
      exposures. The discussion points out the interesting phenomenon of "coasting,"
      the strategy of using neurotrophic factors to combat toxic neuropathies, and the
      inapparent risks in "health foods." Second, it considers toxic myopathy
      syndromes, including zidovudine myopathy and its differentiation from HIV
      associated inflammatory myopathy, cholesterol-lowering agent myopathies, acute
      myopathy with selective loss of myosin filaments due to neuromuscular blocking
      agents and corticosteroids, the eosinophilia myalgia syndrome, and colchicine
      myoneuropathy. Some of these syndromes illustrate important toxicologic
      principles about recognition of rare disorders, unanticipated temporal
      relationships with exposure, and risk factor assessment.

PMID- 8293141
TI  - Electroencephalography and magnetoencephalography in epilepsy and nonepileptic
      disorders.
AB  - Recent advances in electroencephalography (EEG) and magnetoencephalography are
      reviewed. Their relevance to epileptic and nonepileptic conditions is considered.
      The use of intensive video-EEG monitoring for the study or diagnosis of epilepsy
      is addressed. Studies using invasive EEG procedures for seizure analysis with or
      without surgical therapy are described. The integration of EEG with computer
      technologies is increasing, and studies using digital EEG recording and
      quantitative analysis in Alzheimer's disease and other disorders are reviewed.
      Environmental and behavioral effects on EEG are considered. The role of EEG in
      sleep-related electrophysiological monitoring is presented. Progress in
      magnetoencephalography is described, but as a newer technology its usefulness in
      epilepsy and other disorders remains to be proved, especially for clinical
      applications.

PMID- 8293142
TI  - Evoked potentials, magnetic stimulation studies, and event-related potentials.
AB  - With the technique of transcranial magnetic stimulation it is possible to study
      the function of motor pathways in normal subjects and in patients with neurologic
      disease. In conjunction with both evoked and event-related potentials,
      transcranial magnetic stimulation can be used to probe the processes involved in
      analyzing sensory input and in preparing for motor output.

PMID- 8293143
TI  - Peripheral nerve and muscle.
AB  - This review of the past year's literature on neurophysiology of muscles and
      peripheral nerves emphasizes areas with direct clinical interest. The subject is
      diversified but will be discussed under the following major headings: nerve
      conduction studies, electromyography, magnetic motor evoked potentials,
      quantitative sensory testing, assessment of peripheral pain fibers, and autonomic
      function assessment.

PMID- 8293144
TI  - Eye movement disorders.
AB  - The past year's literature on eye movements is characterized by two trends: first
      by the examination of eye movement organization in the three planes of eye
      rotation in normal subjects (there is yet no publication about abnormalities of
      this three-dimensional organization in patients) and second by the increasing
      awareness of clinicians that the characteristics of saccades are highly task
      dependent, and that the saccadic performance of patients must be tested under
      various conditions. Several papers try to establish a correlation between the
      site of a lesion and abnormalities of specific parameters of task-dependent
      saccades. For a better understanding, the different experimental tasks for the
      elicitation of saccades are explained in the text.

PMID- 8293145
TI  - Neuro-ophthalmology: the afferent visual system.
AB  - Recent advances in neuro-ophthalmology have been made in both diagnosis and
      therapy. New discoveries in molecular genetics have resulted in the
      identification of abnormalities in the nuclear and mitochondrial genomes likely
      responsible for retinitis pigmentosa and Leber's hereditary optic neuropathy,
      respectively. Neuroimaging continues to broaden our diagnostic abilities in both
      optic nerve disease and lesions of the retrochiasmal visual pathways. The role of
      steroids in idiopathic optic neuritis has been clarified by the Optic Neuritis
      Treatment Trial. The optic nerve sheath decompression procedure has become a
      useful and effective adjunct in the management of visual loss secondary to
      pseudotumor cerebri, and is currently being evaluated as a potential treatment
      for anterior ischemic optic neuropathy.

PMID- 8293146
TI  - Neuro-otology.
AB  - New techniques for the assessment of vestibulospinal, neck-afferent, and
      viscerograviceptive function may show future clinical applications for a broader
      assessment of balance function in neuro-otological patients. Magnetic resonance
      imaging studies revealed that many intralabyrinthine disorders (labyrinthitis,
      hemorrhage, schwannomas) can be adequately visualized. Perceptual and oculomotor
      clinical studies improved our understanding of vestibular disordered function in
      the roll (coronal) plane. Therapeutic studies highlight the importance of a team
      approach, with individually tailored programs for the rehabilitation of patients
      with vestibular disorders. Reasonable agreement on the criteria for attempting
      hearing preservation during acoustic neuroma surgery seems to have been reached.

PMID- 8293147
TI  - Neurologic rehabilitation.

PMID- 8293148
TI  - Cognitive rehabilitation in neurologic disease.
AB  - Though there has been insufficient good quality research to establish whether
      cognitive rehabilitation of neurologic disease is effective, the present review
      reveals promising preliminary findings for effective rehabilitation in memory,
      neglect, and problem solving deficits. Methodologic weaknesses are, however,
      common in most of the published studies, and it will be some time before it can
      be established how the effects of cognitive rehabilitation following neurologic
      disease can be generalized.

PMID- 8293149
TI  - Physical rehabilitation in neurologic diseases.
AB  - Neurologic diseases, particularly those affecting the central nervous system, are
      the focus of an immense amount of research. Although only a small part of that
      research is directly relevant to rehabilitation, many findings published during
      the last year have implications for practice. Strategies to affect neglect,
      sensory loss, paresis, and functional performance have been examined. Approaches
      as diverse as exercise, feedback, electrical stimulation, patient and environment
      adaptations, orthotics, and task practice have been advocated.

PMID- 8293150
TI  - Disability following head injury.
AB  - Disability following head injury varies depending on injury mechanism,
      neuropathology, and other factors, including medical complications. Mild head
      injury (Glasgow Coma Scale score 13-15) has been shown to have considerable
      variability in outcome. Some persons experience rapid symptom resolution whereas
      others continue to evidence symptoms for an extended duration. A small, but
      clinically significant number of patients may be neuropsychologically and
      occupationally disabled at least up to 1 year postinjury. Methodological problems
      continue to plague mild head injury outcome studies. In contrast, moderate
      (Glasgow Coma Scale score 9-12) and severe head injury (Glasgow Coma Scale score
      3-8) result in more consistent patterns of disability following injury. In
      general, patients who sustain moderate to severe head injury tend to experience
      persistent and extensive neuropsychological, psychiatric, and occupational
      impairment. The impact of rehabilitative interventions is variable and dependent
      on injury severity, intervention type, and outcome criteria.

PMID- 8293152
TI  - Neuromuscular disease.

PMID- 8293151
TI  - Measurement in neurologic rehabilitation.
AB  - The increasing emphasis on evaluating outcomes has led to the development of
      standardized health status measures. Before using one it is vital to check its
      suitability for the intended purpose. Will the measure detect the change or
      difference expected? Other more specific measures should be considered. Some
      focus on common impairments, such as cognitive dysfunction, whereas others focus
      on disabilities seen with specific pathologies such as head injury. Developing
      new measures is difficult and should be avoided if possible.

PMID- 8293153
TI  - Clinical neurophysiology, neuro-otology, and neuro-ophthalmology.

PMID- 8293154
TI  - Neurologic rehabilitation.

PMID- 8293155
TI  - Neurocritical care for coma, intracranial pressure, head injury, and neoplasia.

PMID- 8293156
TI  - Advances in brain tumor imaging.
AB  - Scientists have taken advantage of the powerful imaging capability of computed
      tomographic and magnetic resonance (MR) scanners to analyze brain tumor
      morphology in vivo. Recently, the development of functional MR imaging techniques
      have added the ability to noninvasively examine brain tumor function and
      physiology with near real-time temporal resolution, and spatial resolution
      approaching that of anatomic images. This advance allows the study of cerebral
      blood volume, cerebral blood flow, and stimulated cortical activity, which have
      traditionally been within the domain of positron emission tomography (PET)
      research. PET research on brain tumors continues mainly with research into
      glycolytic rates and comparison with proton MR spectroscopic lactate data. These
      comparisons are facilitated by the refinement of two-dimensional MR spectroscopic
      techniques, which provide comparable spatial resolution to that of PET. On a more
      clinical note, several prospective studies involving the MR contrast agent
      gadolinium have been carried out, specifically those optimizing the timing of
      contrast-enhanced postoperative MR scans after resection of glioblastomas, using
      triple-dose contrast to increase sensitivity to brain metastases, and using
      contrast-enhanced MR imaging to study the efficacy of embolization in
      meningiomas.

PMID- 8293157
TI  - Head trauma.
AB  - Progress in research includes studies concerning the pathophysiology and outcome
      of pediatric head injury, the pathology of the hippocampus in fatal injury, and
      the use of multivariate statistics to predict outcome in survivors. Recent
      research has confirmed and extended findings regarding the differential effects
      of closed head injury, depending on the age of the individual. These studies
      indicate that the consequences of head injury are more severe in older adults and
      in children younger than 2 years. Neuroimaging findings include evidence for
      delayed brain injury as a major cause of mortality and disability. Functional
      brain imaging provides evidence for cerebral dysfunction that is not appreciated
      by structural brain imaging techniques and may have a stronger relationship to
      neurobehavioral sequelae. The neurobehavioral sequelae frequently implicate
      frontal dysfunction, even in the absence of structural findings on computed
      tomography or magnetic resonance imaging. Studies of mild head injury have
      expanded our knowledge concerning the pathogenesis of postconcussional symptoms,
      including a preinjury vulnerability based on recent life events. Persistent
      postconcussional symptoms after mild head injury are frequently associated with
      emotional disturbance of clinical proportions.

PMID- 8293158
TI  - Cerebrospinal fluid circulation, cerebral edema, and intracranial pressure.
AB  - Cerebrospinal fluid (CSF) circulation plays an important role in acute and
      chronic disorders of the central nervous system. Correction of impaired CSF
      circulation by medical or surgical means carries important risks as well as
      lifesaving benefits. CSF circulation is intimately associated with intracranial
      pressure, cerebral edema, cerebral perfusion pressure, and cerebral blood flow.
      Clinical and experimental aspects of the CSF circulation are examined to provide
      insight into the often subtle physiological interactions that must be considered
      when treating patients with altered CSF circulation.

PMID- 8293159
TI  - Vascular and endovascular neurosurgery.
AB  - Vascular lesions of the central nervous system such as aneurysms, arteriovenous
      malformations, tumors, and fistulas are responsible for the majority of
      intracranial hemorrhages seen in the United States. Microneurosurgical techniques
      have enabled neurosurgeons to effectively manage the majority of these lesions.
      Over the past 15 years, microcatheter based treatment modalities have evolved
      which permit access of the distal intracranial and spinal circulation by
      percutaneous cannulation of the femoral artery or vein. Technologic developments
      in polymer science and advances in hydrophilic coatings have produced
      microcatheters less than 1 mm in diameter capable of reaching deep within the
      nidus of arteriovenous malformations or into the body of a cerebral aneurysm.
      Numerous thrombogenic devices are available that can be delivered through
      microcatheters to permanently occlude cerebral vascular abnormalities. Catheter
      technology perfected in the coronary circulation for the management of
      atherosclerotic disease has been used to treat similar lesions of the
      extracranial and intracranial cerebral circulation. Cerebral circulation
      angioplasty for vasospasm has become an accepted technique, and superselective
      drug delivery is growing in popularity. This chapter reviews the recent
      literature in vascular and endovascular neurosurgery in an attempt to familiarize
      the reader with recent advances in the management of cerebrovascular disease.

PMID- 8293160
TI  - Controversy over Werdnig-Hoffmann disease and multiple system atrophy.

PMID- 8293161
TI  - Oligodendroglial and neuronal inclusions in multiple system atrophy.
AB  - Argyrophilic cytoplasmic inclusions of oligodendrocytes have been described in
      cases of multiple system atrophy (olivopontocerebellar atrophy, striatonigral
      degeneration, and Shy-Drager syndrome). The oligodendroglial cytoplasmic
      inclusions are immunolabeled with antiubiquitin antibodies. Ultrastructurally,
      they appear as granule-associated filaments. They have not been found in other
      neurological diseases or in normal brains, and are now considered to be early and
      specific markers of multiple system atrophy. More recently, similar argyrophilic
      inclusion bodies have been reported in the cytoplasm of neurons and in both
      oligodendroglial and neuronal nuclei of multiple system atrophy brains. Neuronal
      and oligodendroglial cytoplasmic inclusions have identical ultrastructural
      characteristics, but different antigenic properties. The chemical nature of the
      inclusions is presently unknown and their significance remains controversial:
      they could be a primary event in the course of the degenerative process or merely
      an epiphenomenon of some disordered cytoskeletal metabolism.

PMID- 8293162
TI  - Meningioma.
AB  - Meningiomas more often behave as benign tumors although their very rate of
      recurrence is unknown. These neoplasms have been exhaustively studied but neither
      their subtypes nor their histologic features were ever considered as reliable
      data of their biologic behavior. Different types of assays have been achieved in
      order to assess the aggressiveness of these neoplasms. The first one concerned
      the mitosis index and different markers of proliferation. Other ways have been
      explored as the dual expression of the differentiation and the steroid receptors
      of the neoplasms, with no evidence of a clear cut prognostic value. Aneuploidy is
      thought to be associated with a rather poor behavior, and chromosome 22 is the
      most frequent abnormality. Recent studies on growth factors related with some of
      the factors previously mentioned and expression of oncogenes complete the
      overview of the methods involved in the search for prognostic data.

PMID- 8293163
TI  - New techniques in neuroimaging: when are pretty pictures clinically useful?

PMID- 8293164
TI  - Interventional neuroradiology.
AB  - Interventional neuroradiology continues to play an increasing role in the
      treatment of intracranial aneurysms, the treatment of vasospasm related to
      subarachnoid hemorrhage, and the treatment of vascular malformations and fistulae
      of the brain and spine. New techniques for aneurysm embolization are examined,
      such as detachable coil systems, as are reports of intracranial angioplasty and
      superselective papaverine infusion for vasospasm following aneurysm rupture.
      Results of investigations of arteriovenous malformation embolizations and recent
      analyses of risk factors associated with arteriovenous malformations are
      discussed. New approaches to tumor embolization are presented, and there are new
      data on angioplasty for cerebral atherosclerotic disease. Local fibrinolytic
      therapy in the treatment of patients with acute intracranial arterial or venous
      sinus thrombosis is evaluated.

PMID- 8293165
TI  - Neuroimaging procedures in acute ischemic stroke.
AB  - Recently, neuroimaging procedures have been applied extensively to the acute
      stage assessment of ischemic brain damage. Positron emission tomography studies
      of brain perfusion and oxygen metabolism performed within 18 hours of stroke
      onset both depict the amount of already irreversibly damaged tissue and
      accurately predict the subsequent neurologic course in a sizeable fraction of
      patients. The prognosis is poor in those patients with extensive irreversible
      damage and good when early spontaneous reperfusion has occurred before cortical
      damage has been established. The remaining patients, in whom ischemia is still
      ongoing and the neurological course is unpredictable, may constitute a subgroup
      more amenable to trials of therapy. New developments in diffusion-weighted
      magnetic resonance imaging suggest this noninvasive tool, like positron emission
      tomography, may be sensitive to failure of energy metabolism very soon after
      ischemia begins. Studies in rats suggest it may be possible to differentiate
      still salvageable tissue from irreversibly compromised tissue with this
      technique. Ultra-fast diffusion-weighted magnetic resonance imaging is feasible
      in humans and preliminary observations suggest the technique is as sensitive in
      humans as it is in rats. The usefulness in acute stroke management of other
      magnetic resonance techniques still in development, such as blood volume and
      perfusion imaging, deoxyhemoglobin-sensitive sequences, and 1H or 31P
      spectroscopy, remains to be assessed.

PMID- 8293166
TI  - Improving imaging contributions to trauma and tumor management.
AB  - The assessment of patients with injuries and tumors is a major proportion of a
      neuroradiologist's workload. Reviewing advances in these important topics
      together in such a short space is a challenge--perhaps even inappropriate.
      Exciting data emerging from Doppler and xenon computed tomography on head injury,
      and magnetic resonance gives new insights into spinal trauma, with significant
      implications for management. Magnetic resonance protagonists pursue their goal of
      proving greater specificity and sensitivity of diagnosis than computed
      tomography, with some justification in the case of benign extra-axial tumors. In
      malignant tumors, data from positron emission tomography emphasize the
      difficulties of defining tumor extent and hence assessing, let alone achieving,
      cure.

PMID- 8293167
TI  - Magnetic resonance imaging in demyelinating, infectious, metabolic, and
      congenital diseases.
AB  - A mere 5 to 7 years ago, the majority of literature on demyelinating, infectious,
      metabolic, and congenital diseases of the brain focused on comparison between
      computed tomography and magnetic resonance imaging (MRI). MRI has become not only
      the foremost diagnostic tool in imaging of the central nervous system, but also a
      key research instrument. This is displayed by the recent increase in papers
      concerning magnetic resonance spectroscopy. It is perhaps no better illustrated
      than in the study of multiple sclerosis. A review of neuroimaging in infectious
      diseases places a heavy emphasis on AIDS-related infections. The ongoing
      development of new scan sequences, contrast agents, and fast scanning techniques
      are broadening our image of the brain and, indeed, our understanding of
      pathophysiologic mechanisms of disease states. Excellent examples of this are the
      metabolic and congenital diseases where, based on the knowledge of metabolic
      pathways and embryology, MRI has become the modality of choice.

PMID- 8293168
TI  - Functional imaging of the central nervous system using magnetic resonance imaging
      and positron emission tomography.
AB  - There have been striking advances recently in magnetic resonance imaging and
      positron emission tomography (PET) imaging of the central nervous system,
      particularly in the area of "functional" imaging. We discuss these advances with
      emphasis on the similarities and differences between the PET and magnetic
      resonance imaging methods. In addition, we examine recent progress and
      controversies in the use of volume-localized nuclear magnetic resonance
      spectroscopy. Finally, we review the use of three-dimensional acquisition for PET
      studies, with an evaluation of the relative advantages and disadvantages of this
      modification of the PET technique.

PMID- 8293169
TI  - Coma, intracranial pressure, intensive care, head injury, and neoplasia.

PMID- 8293170
TI  - Dynamic neuropathology.

PMID- 8293171
TI  - Neuroimaging.

PMID- 8293172
TI  - Immune protection vs. immunopathology vs. autoimmunity: a question of balance and
      of knowledge.
AB  - Immunological mechanisms have been suspected and have been shown to be involved
      in many acute or chronic, and also in some neurological diseases. However, in
      most cases it is unclear whether disease is caused by insufficient immunity,
      delayed immunity against infectious agents or by autoimmunity (i.e., reactivity
      to a "normal" self). The present summary is a biased view of immunological
      pathogenic principles that may explain some of the questions henceforth. Two
      proposals will be illustrated. Firstly, T cell mediated immune protection is
      mediated by cell destruction, i.e., pathology, therefore both beneficial and
      harmful effects of T cell responses against foreign, mostly infectious, antigens
      will be the result of the balance between kinetics of immune response and
      infectious agents. Secondly, if one knows the causative agent, the
      immunologically mediated disease is called "immunopathological" whereas if a new
      or trivial causative agent is not recognized the disease is called "autoimmune".

PMID- 8293173
TI  - The pathogenesis of murine retroviral infection of the central nervous system.
AB  - Several decades have lapsed since the original description of retroviral
      infection of the central nervous system (CNS) appeared. With the recent arrival
      of the autoimmune deficiency syndrome (AIDS) epidemic and the associated human
      retroviral encephalitis, interest in murine models has been rekindled. In most of
      the published studies, susceptible mouse strains are infected as neonates with
      molecularly cloned type-C retroviruses. In most models, a spongiform
      encephalopathy follows an early CNS endothelial cell infection. The subsequent
      pathogenesis of this encephalopathy is unknown. In some models neuronal and glial
      infection is seen, while in others only non-neuroglial elements are infected.
      This variation can be traced to differences in strains of mice and viruses in
      addition to differences in assays. The different models offer fertile
      experimental ground to decipher the role of direct versus indirect neuroglial
      damage. Reconciliation of these various models where the final neuropathology
      appears so similar, may be the key to understanding their pathogenesis.

PMID- 8293174
TI  - Inherited neuropathies: the interface between molecular genetics and pathology.

PMID- 8293175
TI  - Hereditary demyelinating motor and sensory neuropathy.
AB  - The demyelinating hereditary motor and sensory neuropathies (HMSN) are a group of
      inherited progressive neuropathies with markedly decreased nerve conduction
      velocity and chronic segmental demyelination in the peripheral nerve. Inheritance
      is autosomal dominant (AD) or autosomal recessive (AR). Autosomal dominant
      demyelinating HMSN (AD HMSN type I) is genetically heterogeneous and at least
      three different gene loci have been identified: a locus on chromosome 17 (HMSN
      Ia), a locus on chromosome 1 (HMSN Ib) and a locus not linked to chromosome 17 or
      1 (HMSN nonIa-nonIb). HMSN type Ia is the most common form of AD HMSN. Recently,
      it has been demonstrated that the HMSN Ia phenotype results either from a
      duplication of chromosome 17p11.2 or from a point mutation in the peripheral
      nerve-specific PMP-22 gene which is located in the duplication. Pathology of type
      Ia is dominated by chronic segmental demyelination with classical onion bulbs.
      Autosomal recessive demyelinating HMSN shows a broad spectrum of pathological
      features. The genetic defect or defects are not yet known. On the basis of
      morphological characteristics we were able to discern four subtypes. Two AR
      subtypes are clinically and electrophysiologically comparable to AD HMSN type I,
      namely AR HMSN type I with basal lamina onion bulbs and AR HMSN type I with
      focally folded myelin. Two AR subtypes with amyelination, respectively or
      hypomyelination of the peripheral nerves are also more severely affected both
      clinically and electrophysiologically and could be designated as HMSN type III. A
      third condition with a HMSN type III phenotype shows mainly classical onion bulbs
      in peripheral nerves, but the inherited nature of this disorder is uncertain and
      identical features have been described in steroid-responsive inflammatory
      demyelinating neuropathy. The morphologically based subtypes of AR demyelinating
      HMSN may represent different genetic disorders, allelic differences or phenotypic
      variations.

PMID- 8293176
TI  - Hereditary motor and sensory neuropathy: HMSN type II (neuronal type) and X
      linked HMSN.
AB  - The neuronal forms of hereditary motor and sensory neuropathy (HMSN) are
      genetically heterogeneous with observed autosomal dominant, autosomal recessive
      and X-linked dominant inheritance. All three forms are characterized by
      degeneration of select populations of motor and sensory neurons with accompanying
      atrophy and degeneration of their axons. Large calibre myelinated fibres are
      predominantly affected and fibre degeneration and fibre loss progresses from
      distally to proximally. Attempts of regeneration are noted in all except the
      severe childhood form. The clinical picture is that of peroneal and distal leg
      muscle wasting and weakness, distal sensory loss and areflexia. Hand muscles may
      be severely affected in the autosomal recessive and X-linked dominant forms.
      Motor and sensory nerve conduction velocities are only moderately slowed and
      evoked maximum compound motor and sensory amplitudes are reduced according to the
      degree of fibre loss. The gene locus remains unknown in both the autosomal
      dominant and autosomal recessive types. For the X-linked dominant HMSN, the gene
      locus has been mapped closely by linkage analysis to DNA loci in the
      pericentromeric region of the X-chromosome.

PMID- 8293177
TI  - Hereditary sensory neuropathies.
AB  - Hereditary sensory neuropathies have not shared in the major advances that have
      taken place in the molecular genetics of the hereditary demyelinating motor and
      sensory neuropathies. Thus far, classification depends upon their mode of
      inheritance and clinical features. The delineation of the various clinical
      syndromes is still not complete. This is a necessary preliminary to establishing
      the genetic basis of these neuropathies. The hereditary sensory neuropathies can
      be accordingly grouped into those with predominantly sensory and some associated
      autonomic features and those in which a sensory neuropathy is part of a
      spinocerebellar degeneration or other multisystem degeneration.

PMID- 8293178
TI  - Familial amyloid polyneuropathy.
AB  - Familial amyloid polyneuropathy (FAP) is most commonly associated with variant
      plasma transthyretin, although it has also been described in association with
      mutant apolipoprotein A-1 and gelsolin. There are now approximately 26 point
      mutations in the transthyretin gene associated with FAP. Because of the
      overlapping clinical phenotypes described with these mutations, it is now more
      appropriate to classify the various forms of FAP according to the underlying
      genetic defect rather than on clinical grounds. Many questions concerning the
      amyloidogenic nature of transthyretin and the variability of organ involvement
      depending on the underlying mutation remain unanswered. The recent use of liver
      transplantation for treatment appears to be promising.

PMID- 8293179
TI  - Neuropathy associated with mitochondrial disorders.
AB  - Altered mitochondria within peripheral nerves were found in most cases of
      mitochondrial myopathy, in all cases of hereditary motor and sensory neuropathy
      with optic atrophy (HMSN VI) and in 25 cases out of a larger series of 280
      unselected neuropathies studied by electron microscopy for diagnostic purposes.
      The mitochondrial changes differed from those seen in the corresponding skeletal
      muscle fibres. They comprised enlargements with an amorphous matrix and distorted
      cristae, hexagonal paracrystalline inclusions, sometimes longitudinally arranged
      in a zig-zag pattern, prominent cristae containing oblique striations and a
      variety of rare changes. Most mitochondrial abnormalities were found in Schwann
      cells. An occasional perineurial cell was also involved showing a unique
      paracrystalline inclusion. An increase of the number of mitochondria was noted in
      smooth muscle and endothelial cells of epineurial arterioles in three cases of
      mitochondrial encephalomyopathy (two cases with Kearns Sayre syndrome, and one
      with mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes,
      i.e., "MELAS"). Neuropathy was present in all cases of mitochondrial myopathy as
      judged by morphometric analysis. Whether neuropathy is caused directly by
      mitochondrial dysfunction or by other pathogenetic mechanisms remains to be
      determined. Yet peripheral motor and sensory neurons with their peripheral axons
      are postmitotic, terminally differentiated cells which should be similarly prone
      to deleterious deletions of mitochondrial DNA as has been suggested as an
      etiologic factor for the predilection of mitochondrial diseases in muscle and
      brain.

PMID- 8293180
TI  - Paraneoplasia and autoimmunologic injury of the nervous system: the anti-Hu
      syndrome.
AB  - In recent years, antineuronal autoantibodies of varying antigenic specificity
      have come to be associated with a number of paraneoplastic neurologic disorders.
      Anti-Hu is a polyclonal complement-fixing IgG directed against a 35 to 40
      kilodalton protein concentrated in the nuclei of neurons throughout the central
      and peripheral neuraxes. Its elaboration at high titer in serum and cerebrospinal
      fluid is invariably associated with a neurologic syndrome characterized chiefly
      by subacutely evolving sensory neuropathy and an array of central disturbances
      that include bulbar and cerebellar dysfunction, limbic encephalitis and motor
      neuron disease. The manufacture of anti-Hu IgG is triggered in a great majority
      of cases by underlying small cell carcinomas of pulmonary origin, typically
      limited in stage and otherwise silent, that aberrantly express the native
      neuronal antigen or an antigenically indistinguishable epitope. Both neoplastic
      and diseased neural tissues contain lymphocytes of B and T lineage specifically
      cognizant of the Hu antigen as well as concentrated anti-Hu IgG bound to tumor
      cells and neurons, respectively. These observations suggest that an immune
      response serving initially to limit the growth and spread of its inciting
      neoplasm comes subsequently to be misdirected against the nervous system of the
      host, resulting in autoimmunologically-mediated neurologic injury. Clinical,
      neuropathologic and immunologic data derived from a series of 71 sero-confirmed
      cases of the anti-Hu-associated paraneoplastic sensory
      neuronopathy/encephalomyelitis complex are reviewed.

PMID- 8293181
TI  - Polyomavirus models of brain infection and the pathogenesis of multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is generally considered to be an autoimmune disorder with
      myelin as the target and with several unidentified viruses playing ancillary
      roles, possibly through molecular mimicry. Although this paradigm has led to
      important progress on potential mechanisms of myelin loss, neither a target
      antigen in myelin nor a triggering mechanism has yet been identified, leaving the
      etiology of MS still unknown. Animal models of viral demyelination and studies
      showing that JC virus (JCV), the polyomavirus which causes progressive multifocal
      leukoencephalopathy (PML), may be latent in some normal human brains suggest
      another possibility. A host immune response targeting proteins expressed at low
      levels from viral DNA latent in the central nervous system (CNS) might underlie a
      focal demyelinating disease such as MS. A shift from autoimmunity to a latent
      virus model is not a trivial substitution of target antigens. This shift would
      expand the search for a definitive laboratory test for MS and could lead to
      improved therapeutic and preventive approaches.

PMID- 8293182
TI  - A correlative study of p53 protein alteration and p53 gene mutation in
      glioblastoma multiforme.
AB  - The p53 tumor suppressor gene is frequently mutated in glioblastomas. Mutations
      within the p53 gene often result in aberrant expression of the p53 protein
      leading to protein accumulation within the nucleus of the cells which can be
      detected by immunochemistry. Many studies have correlated alterations of p53
      protein expression with p53 gene mutations. Positive staining of tumor cells for
      p53 protein has been widely assumed, perhaps incorrectly, to signify the presence
      of p53 gene mutations. This study compared the immunostaining patterns for p53
      protein in 37 glioblastomas with the molecular genetic data obtained by the
      single strand conformation polymorphism assay. p53 gene mutations were detected
      in 46% (17 of 37) of glioblastomas, while 65% (24 of 37) of glioblastomas were
      positive for protein accumulation by immunohistochemistry. Although 30 of 37
      glioblastomas analyzed showed concordance for p53 protein expression and p53 gene
      mutations, a subset of seven glioblastomas showed discordant accumulation of the
      p53 protein in the absence of any detectable p53 gene mutations. The mdm-2 gene
      was assessed in 17 glioblastomas for gene rearrangements or amplification, but
      none were found. This result suggests that a mechanism other than p53 gene
      mutation can result in altered p53 protein expression.

PMID- 8293183
TI  - Detection of viral DNA in neonatal herpes encephalitis autopsy tissues by
      solution-phase PCR: comparison with pathology and immunohistochemistry.
AB  - To detect DNA sequences of herpes simplex virus (HSV) in neural and non-neural
      tissue sections in disseminated human neonatal HSV infection, a solution
      polymerase chain reaction (PCR) protocol was developed which amplified HSV
      thymidine kinase and host genomic DNA sequences that were hybridized with
      sequence-specific probes in Southern blots. Serial sections of formalin-fixed,
      paraffin embedded autopsy tissues were tested by PCR and compared to histology
      and HSV antigen detection. The sensitivity, specificity and reproducibility of
      this PCR protocol were determined on uninfected and HSV-infected mouse tissues
      and on HSV DNA from infected tissue culture cells. Samples estimated to contain
      as few as 60 copies of preserved HSV DNA target sequence gave a positive PCR
      result. In nine neonates that died during acute HSV infection, all non-neural
      tissues and a minority of neural tissues with histological lesions had HSV
      antigen; when DNA could be amplified, HSV DNA sequences were detected by PCR.
      Together, these findings indicate a direct role for virus in the pathogenesis of
      these lesions. In the same cases, some or all brain samples were negative for HSV
      antigen, but nevertheless had HSV DNA sequences detected by PCR. The possible
      explanations for this finding are discussed. In one neonate dying seven weeks
      after birth, HSV sequences were found in brain lesions in the absence of HSV
      antigen; neither HSV DNA nor antigen were found in non-neural tissues, suggesting
      a latent HSV infection in brain. It is practical to apply PCR methods to detect
      minute quantities of viral DNA in formalin-fixed, paraffin embedded autopsy
      tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293184
TI  - Brain tumours: morphological aspects and classification.

PMID- 8293185
TI  - The new WHO classification of brain tumours.
AB  - The new edition of the World Health Organization (WHO) book on 'Histological
      Typing of Tumours of the Central Nervous System' reflects the progress in brain
      tumour classification which has been achieved since publication of the first
      edition in 1979. Several new tumour entities have been added, including the
      pleomorphic xanthoastrocytoma, central neurocytoma, the infantile desmoplastic
      astrocytoma/ganglioglioma, and the dysembryoplastic neuroepithelial tumour. The
      list of histological variants has also been expanded. In line with recent
      morphological and molecular data on glioma progression, the glioblastoma is now
      grouped together with astrocytic tumours. The classification of childhood tumours
      has been largely retained, the diagnosis primitive neuroectodermal tumour (PNET)
      only being recommended as a generic term for cerebellar medulloblastomas and
      neoplasms that are histologically indistinguishable from medulloblastoma but
      located in the CNS at sites other than the cerebellum. The WHO grading scheme was
      revised and adapted to new entities but its use, as before, remains optional.

PMID- 8293186
TI  - Pleomorphic xanthoastrocytoma: the birth of a diagnosis and a concept.
AB  - This review deals with one of the newly adopted entities in the second edition of
      the histologic typing of CNS tumours by the World Health Organization:
      pleomorphic xanthoastrocytoma and reviews the clinical features, gross and
      microscopic characteristics as well as the common and some of the unusual
      variants of this tumor. The steps and events leading to the recognition of the
      basic character of this neoplasm and its designation as an independent entity are
      recollected and a few characteristic MRI scans and photomicrographs of
      pleomorphic xanthoastrocytomas are provided.

PMID- 8293187
TI  - Desmoplastic infantile ganglioglioma and desmoplastic cerebral astrocytoma of
      infancy.
AB  - The desmoplastic infantile ganglioglioma and desmoplastic cerebral astrocytoma of
      infancy are rare neoplasms arising in the cerebral hemispheres within the first
      two years of life which are defined by a combination of distinctive
      clinicopathologic features. The tumours are massive, partially cystic and
      invariably occur in a supratentorial location. Involvement of multiple lobes is
      common with a predilection for frontoparietal areas. In one series of 22
      desmoplastic infantile gangliogliomas, all patients presented between 2 and 24
      months of age (mean = 6 months; median = 4 months) with a male to female ratio of
      1.4:1. In the nine reported cases of the desmoplastic cerebral astrocytoma of
      infancy, all patients presented between 1.5 and 14 months of age (mean = 6.8
      months; median = 6 months) with a male to female ratio 0.8:1. The hallmark
      feature of both neoplasms is an abundant and often dense desmoplasia, imparting a
      characteristic firmness to the neoplasms. In the desmoplastic infantile
      gangliogliomas, astroglial and neuronal tumour cells in addition to variable
      numbers of more primitive, mitotic cells comprise the neoplastic neuroepithelial
      populations. In contrast, the neuroepithelial component of the desmoplastic
      infantile astrocytomas is restricted to neoplastic astrocytes. Despite the large
      size, cellular pleomorphism and cellular atypia, prognosis following successful
      surgical resection in both types of tumours is quite favorable. The longest
      followup data is available for the desmoplastic infantile gangliogliomas. With
      the median interval of 8.7 years (range 1 to 14.5 years) following surgery for 14
      patients in this series, there were no deaths due to tumour or any evidence of
      tumour recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293188
TI  - Dysembryoplastic neuroepithelial tumours.
AB  - Dysembryoplastic neuroepithelial tumours (DNTs) are a group of supratentorial
      cortical benignant lesions that superficially resemble mixed oligo-astrocytomas,
      oligodendrogliomas or astrocytomas. Clinically these tumours are associated with
      partial seizures beginning before the age of 20 years, with no neurologic deficit
      and no stigmata of phacomatosis. In the revised WHO classification, DNTs have
      been incorporated among the category of neuronal and mixed neuronoglial tumours.
      This classification describes a histologic variant characterized by the following
      criteria: cortical location, multinodular architecture--the nodule being made of
      multiple variants looking like astrocytomas, oligodendrogliomas or oligo
      astrocytomas, foci of dysplastic cortical disorganization and the presence of a
      glioneuronal element showing a columnar structure perpendicular to the cortical
      surface. A study of 14 cases for which only a specific glioneuronal element could
      be identified demonstrated that this specific element is sufficient for
      diagnosing DNTs and that the spectrum of DNTs includes a simple form with a
      unique glioneuronal element. Preoperative imaging follow-up data, in the series
      of 23 simple and complex forms, indicated that DNTs are perfectly stable.
      However, these tumours may show a high MIB 1 labeling index.

PMID- 8293189
TI  - Central neurocytoma: a synopsis of clinical and histological features.
AB  - The central neurocytoma is a supratentorial, often calcified brain tumour
      affecting young adults and is typically located in the lateral ventricles in the
      region of the foramen of Monro. Clinically, the tumour causes signs of increased
      intracranial pressure, visual and mental disturbances and, occasionally,
      pyramidal or endocrine symptoms. By light microscopy, the tumour is composed of
      small round cells in a delicate fibrillary matrix. Tumour cells consistently show
      features of neuronal differentiation by electron microscopy (synapses, dense-core
      vesicles, presynaptic clear vesicles, specialized synaptic junctions) and
      immunoreactivity for synaptophysin and other neuronal marker proteins. The tumour
      can be totally removed in nearly half of the cases. After incomplete surgical
      resection neurocytomas may recur but because of their low proliferation
      potential, radio- or chemotherapy are not generally recommended. Postoperative
      recurrence-free survival times of up to 19 years have been reported. Neurocytomas
      constitute nearly one half of supratentorial intraventricular tumours in adults
      but amount to less than 1% of all tumours of the central nervous system and its
      coverings.

PMID- 8293190
TI  - The immunopathology of Alzheimer's disease and some related disorders.
AB  - Current evidence clearly indicates that elements of the immune system are
      involved in the pathogenesis of the principal lesions characterizing Alzheimer's
      disease (AD). Findings are in accord with features associated with both the
      innate and adaptive immune mechanisms involved in a predominantly local
      inflammatory response within the parenchyma. Many of the features are unique to
      AD, presumably related to the unusual properties of beta amyloid protein.
      Remarkably, the brain holds the capacity to produce almost all the immune system
      mediators which largely seem to be generated by glia comprising both astrocytes
      and microglia. While a variety of humoral mediators including classical acute
      phase proteins (and serpins) are increased and released, the complement seems
      most intrinsically involved. The cellular response is elaborated by microglia
      which seem the main immunocompetent cells partaking in the response. These appear
      to function as pluripotent macrophages expressing both classes of MHC antigens.
      Further characterization of this interesting response to cerebral amyloidosis
      will be challenging.

PMID- 8293191
TI  - Cytochrome C oxidase deficiency and neuronal involvement in Menkes' kinky hair
      disease: immunohistochemical study.
AB  - Antibodies against subunits II and IV of cytochrome c oxidase (COX) and against
      complex III of the respiratory chain were used to study the expression of these
      proteins in the cerebellum, spinal cord, and other regions of the central nervous
      system in an autoptic case of Menkes' kinky hair disease (MKHD). We found a
      reduced expression of COX subunits in all examined areas whereas staining for
      complex III appeared normal. Immunostaining was altered in morphologically well
      preserved neurons, suggesting that COX deficiency may have a pathogenetic role in
      the neuronal degeneration of MKHD.

PMID- 8293192
TI  - Searching for human epilepsy genes: a progress report.
AB  - Application of new genetic techniques has brought remarkable discoveries in the
      study of genetic diseases. The potential benefits from applying such technology
      to idiopathic epilepsies include improved understanding of cellular mechanisms
      and potential new methods of prevention and treatment. The complex problems
      involved in studying the hereditary epilepsies include: defining of specific
      phenotypes; detecting genetic and non-genetic heterogeneity; and specifying the
      appropriate mode of inheritance and penetrance. The gene loci for three primary
      epilepsies have been localized to specific chromosomal regions, and serve to
      demonstrate the process used in generalized linkage studies of hereditary
      epilepsy syndromes. Benign familial neonatal convulsions (BFNC) and Unverricht
      Lundborg progressive myoclonus epilepsy are rare single-gene disorders that are
      sufficiently localized to chromosomal regions that positional cloning studies are
      likely to succeed. Juvenile myoclonic epilepsy (JME), a common hereditary
      syndrome with an uncertain mode of inheritance, has been reported to be linked to
      chromosome 6p. JME presents a challenge for generalized linkage methodology that
      may be overcome by attending to potential problems reviewed here. The candidate
      gene method, combined with studies using animal models, holds promise for
      understanding these as well as other hereditary epilepsies.

PMID- 8293193
TI  - Surgical pathology of chronic epileptic seizure disorders.
AB  - The surgical treatment of chronic epilepsies is increasing rapidly and involves
      neuropathologists in the care of patients with chronic and medically intractable
      seizure disorders. Herein we review the histopathologic findings in 279
      consecutive surgical specimens of patients with chronic pharmacoresistant
      epileptic disorders. Aspects that are relevant to the diagnostic surgical
      pathologist such as the terminology of developmental lesions and Ammon's horn
      sclerosis are discussed. In 87 cases (31.2%), there were tumors in which all but
      two were of low histopathological grade (WHO grade I or grade II). The most
      common tumors were gangliogliomas, pilocytic astrocytomas, oligodendrogliomas,
      fibrillary astrocytomas and dysembryoplastic neuroepithelial tumors. Among the
      most frequent non-neoplastic focal lesions, microscopic glioneuronal hamartias,
      circumscribed vascular malformations, glioneuronal hamartomas and porencephalic
      defects were most frequent. The hippocampal formation was structurally well
      preserved in 71 specimens of patients with temporal lobe epilepsy. In 51 of these
      (71.8%) cases, Ammon's horn sclerosis was present. The findings suggest that the
      structural lesions observed in the great majority of the specimens are closely
      related to the pathogenesis of intractable seizures.

PMID- 8293194
TI  - Immediate early gene expression in experimental epilepsy.
AB  - Neuronal excitation by experimentally induced seizures elicits the rapid
      induction of a set of genes called immediate early genes (IEGs). The gene
      products of fos, jun and Krox, multimember gene families that belong to the class
      of IEGs, participate in a fundamental biological control mechanism, the
      regulation of gene transcription. IEG encoded proteins act as third messengers in
      an intracellular signal transduction cascade between neural cell surface
      receptors, cytoplasmic second messenger systems and specific target genes in the
      nucleus, a process for which the term 'stimulus transcription coupling' has been
      given. Almost all types of seizures cause dynamic alterations of IEG expression
      in neurons of the limbic system, but also in non-limbic areas, such as the
      cortex, striatum and thalamus. IEG encoded transcription factors are thought to
      up- or down-regulate effector genes with preferential expression in the central
      nervous system, including genes for neurotransmitters, growth factors, receptors,
      synaptic and axonal proteins. If the concept holds true that IEGs act as
      molecular switches converting epileptic short-term excitation of neurons into
      alterations of the molecular phenotype, future research may help to explain
      hitherto unexplained phenomena in epileptogenesis including changes of synaptic
      efficacy, kindling and sprouting.

PMID- 8293195
TI  - The molecular basis of kindling.
AB  - Kindling is an experimental model of epilepsy that involves activity-dependent
      changes in neuronal structure and function. During kindling, pathological changes
      may occur at several organizational levels of the nervous system, from
      alterations in gene-expression in individual neurons to the loss of specific
      neuronal populations and rearrangement of synaptic connectivity resulting from
      sustained stimulation of major excitatory pathways. This review summarizes recent
      developments in alterations at single neuronal and molecular levels that may be
      responsible for kindling epileptogenesis.

PMID- 8293196
TI  - Excitotoxicity and selective neuronal loss in epilepsy.
AB  - The early stages of selective neuronal loss occurring in the hippocampus and
      other brain regions after prolonged epileptic activity have fine structural
      characteristics matching those induced by excitotoxic agents. NMDA receptor
      antagonists provide protection against such damage. The extracellular
      concentration of glutamate or aspartate may be transiently raised prior to or
      early in seizure activity but tends not to match the levels associated with
      hypothalamic damage in the original paradigm of excitotoxicity. Various aspects
      of the excitotoxic process are examined to see if they can account for particular
      details of the pattern of selective neuronal loss. A full explanation of
      selective vulnerability will take into account not only a range of
      characteristics of the vulnerable neuron but also its functional network during
      sustained activity.

PMID- 8293197
TI  - Consequence of epileptic activity in vitro.
AB  - Hippocampal sclerosis: a cause or consequence of epileptic activity? This
      question has concerned neurologists and pathologists for over 150 years. This
      paper reviews data from an in vitro model system regarding the consequences of
      epileptic activity of known origin. Exposure of organotypic hippocampal slice
      cultures to convulsants, such as bicuculline or picrotoxin for three days leads
      to pronounced neuronal degeneration and a reversible loss of dendritic spines. A
      similar pathology has been described in hippocampal tissue removed from patients
      suffering from severe, drug refractory epilepsy. The consequences of such
      pathological changes are not self-sustaining epileptic activity, as might be
      expected if such sclerosis caused epilepsy, but rather a selective decrease in
      synaptic excitation. Inhibitory synaptic transmission and GABAergic interneurons,
      in contrast, are preserved. At least two mechanisms contribute to the depression
      of synaptic excitation: morphological changes in dendritic spines and a decrease
      in the expression of genes for some glutamatergic receptors. It is hoped that
      this model will allow the characterization of the mechanisms underlying the
      pathological consequences of epileptic activity, and lead to useful therapeutic
      strategies.

PMID- 8293198
TI  - Non-radioactive direct sequencing of PCR products amplified from
      neuropathological specimens.
AB  - We have developed a simple, rapid and relatively inexpensive protocol for direct
      non-isotopic cycle sequencing of DNA amplified using the polymerase chain
      reaction (PCR). PCR is performed on routine and archival neuropathological
      tissue. For sequencing, a 5'-digoxigenin end-labelled oligonucleotide primer is
      annealed and extended during thermal cycling, sequencing reactions are separated
      on a standard sequencing gel and the gel is contact-blotted to a nylon membrane.
      Sequenced DNA is visualized using immunological detection of digoxigenin.

PMID- 8293199
TI  - August Forel--cofounder of the neuron theory (1848-1931).

PMID- 8293200
TI  - Bioethics: the dangers of rhetoric.

PMID- 8293201
TI  - Must good causes compete?

PMID- 8293202
TI  - Jeremy Bentham and the patient in room 326.

PMID- 8293203
TI  - Pipes, colanders, and leaky buckets: reflections on the futility debate.

PMID- 8293204
TI  - Medical futility: the duty not to treat.

PMID- 8293205
TI  - Helga Wanglie revisited: medical futility and the limits of autonomy.

PMID- 8293206
TI  - The Wanglie case from an Uruguayan perspective.

PMID- 8293207
TI  - The ethics of withholding and withdrawing critical care.

PMID- 8293208
TI  - Prognostic scoring systems: facing difficult decisions with objective data.

PMID- 8293209
TI  - Ethical implications of risk stratification in the acute care setting.

PMID- 8293210
TI  - Medical futility in resuscitation: value judgement and clinical judgement.

PMID- 8293212
TI  - Medical futility.

PMID- 8293211
TI  - Futility: is definition the problem? Part I.

PMID- 8293213
TI  - The story of Laurens.

PMID- 8293214
TI  - Acting or letting go: medical decision making in neonatology in The Netherlands.

PMID- 8293215
TI  - Force majeure (legal necessity): justification for active termination of life in
      the case of severely handicapped newborns after forgoing treatment.

PMID- 8293216
TI  - Actively ending the life of a severely handicapped newborn: a Dutch ethicist's
      perspective.

PMID- 8293217
TI  - A paradigm for making difficult choices in the intensive care nursery.

PMID- 8293218
TI  - Legal issues in treating critically ill newborn infants.

PMID- 8293219
TI  - The role of women in abortion jurisprudence: from Roe to Casey and beyond.

PMID- 8293220
TI  - In vitro fertilization: regulations in Germany.

PMID- 8293221
TI  - From cells to selves: ethics at the beginning of life.

PMID- 8293222
TI  - Impaired physicians: what should patients know?

PMID- 8293223
TI  - The United States Bishops' Committee statement on nutrition and hydration.

PMID- 8293224
TI  - Michael Tooley on possible people and promising.

PMID- 8293225
TI  - The outpatient management of a brain dead child.

PMID- 8293226
TI  - Malpractice liability for the failure to adequately educate patients: the
      Australian law of "informed consent" and its implications for American ethics
      committees.

PMID- 8293227
TI  - Evolutionary artificial neural networks.
AB  - Evolutionary artificial neural networks (EANNs) can be considered as a
      combination of artificial neural networks (ANNs) and evolutionary search
      procedures such as genetic algorithms (GAs). This paper distinguishes among three
      levels of evolution in EANNs, i.e. the evolution of connection weights,
      architectures and learning rules. It first reviews each kind of evolution in
      detail and then analyses major issues related to each kind of evolution. It is
      shown in the paper that although there is a lot of work on the evolution of
      connection weights and architectures, research on the evolution of learning rules
      is still in its early stages. Interactions among different levels of evolution
      are far from being understood. It is argued in the paper that the evolution of
      learning rules and its interactions with other levels of evolution play a vital
      role in EANNs.

PMID- 8293228
TI  - Fast learning of biased patterns in neural networks.
AB  - Usual neural network gradient descent training algorithms require training times
      of the same order as the number of neurons N if the patterns are biased. In this
      paper, modified algorithms are presented which require training times equal to
      those in unbiased cases which are of order 1. Exact convergence proofs are given.
      Gain parameters which produce minimal learning times in large networks are
      computed by replica methods. It is demonstrated how these modified algorithms are
      applied in order to produce four types of solutions to the learning problem: 1. A
      solution with all internal fields equal to the desired output, 2. The Adaline (or
      pseudo-inverse) solution, 3. The perceptron of optimal stability without
      threshold and 4. The perceptron of optimal stability with threshold.

PMID- 8293229
TI  - Weight configurations of trained perceptrons.
AB  - We strive to predict the function mapping and rules performed by a trained
      perceptron from studying the weights. We derive a few properties of the trained
      weights and show how the perceptron's representation of knowledge, rules and
      functions depend on these properties. Two types of perceptrons are studied--one
      case with continuous inputs and one hidden layer, the other a simple binary
      classifier with boolean inputs and no hidden units.

PMID- 8293230
TI  - The ClusNet algorithm and time series prediction.
AB  - This paper describes a novel neural network architecture named ClusNet. This
      network is designed to study the trade-offs between the simplicity of instance
      based methods and the accuracy of the more computational intensive learning
      methods. The features that make this network different from existing learning
      algorithms are outlined. A simple proof of convergence of the ClusNet algorithm
      is given. Experimental results showing the convergence of the algorithm on a
      specific problem is also presented. In this paper, ClusNet is applied to predict
      the temporal continuation of the Mackey-Glass chaotic time series. A comparison
      between the results obtained with ClusNet and other neural network algorithms is
      made. For example, ClusNet requires one-tenth the computing resources of the
      instance-based local linear method for this application while achieving
      comparable accuracy in this task. The sensitivity of ClusNet prediction
      accuracies on specific clustering algorithms is examined for an application. The
      simplicity and fast convergence of ClusNet makes it ideal as a rapid prototyping
      tool for applications where on-line learning is required.

PMID- 8293232
TI  - Neural strategies to handle routing in computer networks.
AB  - In this paper, the authors adopt a neural approach to deal with the problem of
      routing in a packet switching network. The aim is to define a routing strategy
      which will combine the advantages of both the centralized and the distributed
      approaches. The neural approach presented is based on the idea of inserting a
      neural network (N/N) into each node in the computer network which will be
      responsible for computing the route between its node and the immediately adjacent
      one. Two distributed routing solutions are presented in the paper based on an
      optimizing network and a mapping network. The routing obtainable and the
      implementation resources needed for the two approaches are evaluated. Finally,
      the performance offered by the neural strategies proposed is compared with that
      offered by classical distributed and centralized routing solutions. As a
      parameter of merit, the effect of overloading caused by the additional traffic
      present in each solution is used.

PMID- 8293231
TI  - A flexible and fault tolerant query-reply system based on a Bayesian neural
      network.
AB  - A query-reply system based on a Bayesian neural network is described. Strategies
      for generating questions which make the system both efficient and highly fault
      tolerant are presented. This involves having one phase of question generation
      intended to quickly reach a hypothesis followed by a phase where verification of
      the hypothesis is attempted. In addition, both phases have strategies for
      detecting and removing inconsistencies in the replies from the user. Also
      described is an explanatory mechanism which gives information related to why a
      certain hypotheses is reached or question asked. Specific examples of the systems
      behavior as well as the results of a statistical evaluation are presented.

PMID- 8293233
TI  - Dynamics of antagonistic neural processing elements.
AB  - Two coupled nonlinear first-order systems whose dynamic behavior reflects the
      neural states exhibited by a spatially localized population of excitatory and
      inhibitory nerve cells are described. The dynamics of each constituent neural
      subpopulation represents a fundamental neural information processing element (PE)
      of a complex neural system. Phase plane analysis is used in this paper to show
      how such antagonistic positive acting (excitatory) and negative acting
      (inhibitory) PEs can generate diverse steady-state and temporal phenomena when
      the nonlinear system parameters of the PEs are altered. By modifying a selected
      set of parameters, it is possible to program the positive and negative PEs to
      exhibit various dynamic attributes such as multiple stable states, transient
      response behavior and limit-cycle oscillations. These dynamic attributes may be
      used to perform a variety of useful computational tasks in signal processing and
      vision systems such as short-term memory (STM), temporal filtering (TF) and pulse
      frequency modulation (PFM). Computer simulations are presented throughout this
      paper in order to illustrate these dynamic attributes.

PMID- 8293234
TI  - Senior house officers: the lost tribes.

PMID- 8293236
TI  - Risk management, loss control and the autopsy.

PMID- 8293235
TI  - Active management of problem patients.

PMID- 8293237
TI  - Acute ischaemia of the upper limb.
AB  - Acute upper limb ischaemia, although rare, may have tragic consequences if the
      outcome is less than satisfactory. Surgical intervention produces superior
      results and should be considered in all cases.

PMID- 8293238
TI  - Phantom limb pain.
AB  - Phantom limb pain is a common sequel to amputation, whether traumatic or
      surgical. Provision of a pain-free interval before surgery is likely to reduce
      the incidence of the condition. The possible mechanisms of pain perception in an
      absent body part and the reasons for the frequent failure of conventional therapy
      are discussed here.

PMID- 8293239
TI  - Current management of breast cancer.
AB  - The last decade has seen many changes in the management of breast cancer, both in
      surgical treatment and in systemic therapy, which can reduce the mortality rate
      by 25%. At the same time attention has turned to improving not only length of
      survival but also quality of life. These changes plus new developments in breast
      cancer treatment are reviewed here.

PMID- 8293240
TI  - Pathophysiological causes and clinical significance of flushing.
AB  - Flushing is a common and important symptom, resulting from changes in cutaneous
      blood flow. It occurs as part of a number of endocrine syndromes, and may be
      caused pharmacologically. Effective management depends on accurate diagnosis and
      understanding of the mechanisms involved.

PMID- 8293241
TI  - Current concepts in Reye's syndrome.
AB  - Reye's syndrome is an acute metabolic encephalopathy largely affecting children
      and adolescents. Its aetiopathogenesis, although controversial, is at least
      partially understood. Its study has helped to create a greater awareness of
      inherited disorders of intermediary metabolism. Although these are individually
      rare, when combined they constitute a significant cause of morbidity and
      mortality.

PMID- 8293242
TI  - Selecting for specialist training: 1.
AB  - Selection for specialist training posts is handled in an amateurish way by the
      NHS. To a considerable extent, future specialists select themselves, but often
      without sound reasoning. Few specialties have studied what, if any,
      characteristics are essential or desirable and so are unable to generate either a
      proper job specification or person specification. These are essential for success
      when selecting by interview.

PMID- 8293243
TI  - The art of good prescribing.
AB  - This article is designed to help consultants to improve patient compliance and
      avoid serious drug reactions. It also considers the legitimacy of placebos.

PMID- 8293244
TI  - Doppler ultrasound in obstetric practice: 1.
AB  - The Doppler effect has been recognized for around 150 years. The practical
      application of the phenomenon to the study of fetomaternal haemodynamics has been
      applied for almost 20 years. This article considers the theory of the effect in
      relation to obstetric practice.

PMID- 8293245
TI  - Improving the management of acute pain.
AB  - The management of acute postoperative pain has been the subject of much interest
      in the last 3 years. Better use of current drugs by changing methods of delivery
      and better education of staff have led to an improvement in the care of patients
      in pain. Attention to detail and vigilance can prevent the unwanted effects of
      respiratory depression and nausea.

PMID- 8293246
TI  - Reservations about the implementation of the New Deal.

PMID- 8293248
TI  - Indications for TIPSS need clarification. Transjugular intrahepatic portosystemic
      stent-shunts.

PMID- 8293247
TI  - Reservations about the implementation of the New Deal.

PMID- 8293249
TI  - Indications for TIPSS need clarification. Transjugular intrahepatic portosystemic
      stent-shunts.

PMID- 8293250
TI  - Risk of anticoagulant-related ICH.

PMID- 8293251
TI  - BIR presidential address: the challenge of change.

PMID- 8293252
TI  - The biology and radiobiology of in utero development in relation to radiological
      protection.
AB  - Aspects of intrauterine development relevant to radiological protection but not
      considered in the recently revised Recommendations of ICRP (1991a) include (i)
      recently acquired evidence on the totipotency of cells of the morula with
      implications for dosimetry and risk in the first week of human development in
      utero; (ii) much older evidence on the earliest stages of myelo- and
      lymphopoiesis in the human subject that bears on radiosensitivity to leukaemia
      induction in utero; (iii) much older evidence on species differences that may
      affect the application to the human of experimental work on radionuclide
      transport from mother to embryo and fetus; (iv) recent proposals of alternative
      mechanisms for localization of functions in the developing mammalian forebrain
      with implications for risk of mental impairment caused by low level irradiation
      in utero, and (v) a recent demonstration that UNSCEAR (1977) was mistaken when
      concluding that a high radiosensitivity for teratogenesis is characteristic of
      the embryo and of preimplantation irradiation. The 1990 Recommendations of ICRP
      (1991a) to limit exposure of the fetus to radionuclides by reference to the
      occupation ALI for adults, i.e. women of reproductive age, seems to be a serious
      mistake.

PMID- 8293253
TI  - Fast magnetic resonance angiography using turbo-FLASH sequences in advanced
      aortoiliac disease.
AB  - A prospective study using contrast enhanced turbo-FLASH (Fast Low-Angle Shot)
      magnetic resonance (MR) angiography was performed to assess the arterial anatomy
      in patients who had advanced atherosclerotic aortoiliac disease. This new imaging
      sequence was employed in 17 patients and the results were compared with
      conventional abdominal aortography. MR angiography accurately detected all aortic
      occlusions (3/3), their sites and their extent. All nine iliac occlusions were
      correctly identified (sensitivity 100%, specificity of 90%). The sensitivity was
      100% for stenosis of 50% or greater in the abdominal aorta, and the iliac and
      common femoral arteries. The degree of stenosis was overgraded in 20 of 51
      lesions (39.2%). Mild stenosis was overgraded as moderate stenosis in 10 and as
      severe stenosis in three. Moderate stenosis was overgraded as severe stenosis in
      four. None of the mild or moderate stenoses resulted in areas of signal voids
      suggestive of occlusions. Three severe stenoses were seen as areas of signal
      voids (two iliac, one femoral). In the eight patients who had in total 10
      aneurysmal dilatations of the aorta or the iliac arteries, MR angiography was
      superior in demonstrating the true extent of the aneurysms. We conclude that
      turbo-FLASH MR angiography has the potential to be a useful non-invasive imaging
      technique for patients with advanced aortoiliac disease.

PMID- 8293254
TI  - Isolated atraumatic third nerve palsy: clinical features and imaging techniques.
AB  - We have reviewed 34 consecutive patients imaged for an isolated third nerve palsy
      over a 2-year period. With pupil sparing the third nerve palsy was most often due
      to ischaemic microvascular disease. The commonest cause of a third nerve palsy
      with pupillary involvement was a posterior communicating artery aneurysm.
      Clinical features such as speed of onset, pain and completeness of palsy were not
      reliable in the diagnosis of either the nature or the location of the cause.
      Pupillary involvement was however often associated with a compressive lesion.
      Imaging along the whole course of the nerve is recommended for adequate
      evaluation.

PMID- 8293255
TI  - Computed tomography in sternocostoclavicular hyperostosis.
AB  - Sternocostoclavicular hyperostosis is a rare but recognized entity characterized
      by new bone formation and ligamentous ossification which limits mobility of the
      sternoclavicular joints. Aetiology is obscure and debated. There may be
      considerable delay in establishing the diagnosis, even by specialists. In
      confirming the diagnosis plain radiography is of limited value but radionuclide
      bone scan and computed tomography (CT) may be helpful. Four cases are described
      to emphasize these points and illustrate the clinical and radiological features
      of the condition. High resolution CT with thin sections (5 mm or less) is the
      examination of choice for demonstrating the characteristic features and is
      essential if the condition is to be confirmed in its early stages when treatment
      might be more successful in delaying progression.

PMID- 8293256
TI  - The role of intravenous cholangiography in pre-operative assessment for
      laparoscopic cholecystectomy.
AB  - With the advent of laparoscopic cholecystectomy, pre-operative identification of
      calculi in the common bile duct has become increasingly important. In patients
      without clinical or biochemical evidence of common bile duct calculi, debate
      continues as to the value of intravenous cholangiography (IVC) as a screening
      modality for the detection of unsuspected choledocholithiasis. In a prospective
      series of 180 patients, IVC was used to assess the common bile duct in 113
      patients at low risk of choledocholithiasis, 51 patients at high risk underwent
      endoscopic retrograde cholangiography (ERC) and sphincterotomy if indicated, and
      in 16 patients, for a variety of reasons, no pre-operative cholangiography was
      performed. 31% of those who had ERC and two (1.8%) of those who had IVC had duct
      calculi. These data do not support the routine use of IVC in patients with no
      evidence of common bile duct calculi and its routine use has been discontinued.

PMID- 8293257
TI  - A comparative study of velocity measurements in major blood vessels using
      magnetic resonance imaging and Doppler ultrasound.
AB  - Velocity measurements in major blood vessels were obtained in studies of
      volunteers using magnetic resonance imaging (MRI) and compared with Doppler
      ultrasound (US). The vessels studied were the abdominal aorta, superior
      mesenteric artery, common carotid artery, superficial femoral artery and middle
      cerebral artery. Using a paired t-test, no significant difference was found
      between velocity values estimated by MRI and US (p > 0.08). The relative
      advantages of each technique in radiological practice are discussed.

PMID- 8293258
TI  - Bone loss in normal British women; a 5 year follow-up.
AB  - To assess the rates of loss, forearm and spinal bone mineral were remeasured in
      16 out of 18 peri- and post-menopausal women aged 45 to 60 years who had taken
      part in a previously reported cross-sectional study. The mean interval between
      measurements was 4.8 years (range 4.2-5.3 years). The mean (95% confidence
      interval (CI)) annual change in radial bone mineral density was -0.78%/year (
      1.73 to +0.18%; not significant) and in spinal bone mineral -2.41%/year (-3.55 to
      1.27%; p < 0.001). There was considerable variation in the rate of change in
      radius and spine, and between individuals. There was no significant correlation
      between rates of bone loss at either site, or between rates of loss and the
      initial bone density at either the radius or spine. There was no significant
      correlation between the rates of change and the age or number of years post
      menopause of the women. There was no significant change in the Z score for the
      forearm (mean -0.20; 95% CI -0.65 to +0.25) or for the spine (mean -0.04; 95% CI 
      0.30 to +0.22). There have been no previous longitudinal studies of the changes
      of bone density in normal British women. These results show considerable
      variation between individuals, and rates of change at one site cannot be
      predicted from measurements at another site. Untreated, some normal individuals
      have high rates of loss that cannot be predicted from baseline values, age or
      number of years post-menopause.

PMID- 8293259
TI  - A comparison of reference bone mineral density measurements derived from two
      sources: referred and population based.
AB  - The construction of reference ranges for bone mineral density (BMD) is of
      importance when defining risk of osteoporosis in an individual. This study
      examined lumbar spine BMD from two different populations of women aged 40-69
      years, both measured by dual X-ray absorptiometry (DXA) using Hologic QDR-1000
      machines. Results were compared with the manufacturer's reference range. At one
      site (Centre 1) women were referred by general practitioners for BMD measurement
      to aid decisions regarding long term hormone replacement therapy (HRT). At the
      other (Centre 2), women were drawn from the age/sex register of a London general
      practice (population 11,000) and invited to attend a screening examination at
      their local hospital. The BMD for both groups did not differ significantly from
      the manufacturer's reference range. The BMD at Centre 1 was lower than Centre 2
      by 0.0175 g cm-2 but this did not reach significance and after calibration of
      both DXA machines with a spine phantom the difference in BMD of the two groups
      was reduced to only 0.0034 g cm-2. Population based sampling carries no advantage
      over a GP referral based method for the construction of spinal BMD reference
      ranges. Although local BMD reference ranges may be required for sites outside the
      spine the comparable results in this study of the two UK reference ranges and
      those of the USA manufacturer suggest that local reference ranges for lumbar
      spine BMD using DXA may be unnecessary in the UK.

PMID- 8293260
TI  - A frameless method for stereotactic radiotherapy.
AB  - A frameless method for stereotactic multiple arc radiotherapy (SMART) is
      described. Three short gold wires are implanted in the scalp approximately 100 mm
      apart. These are localized in a computed tomographic or angiographic study along
      with the target. Subsequently the gold markers are localized on beam films and
      the target position calculated using a computer program ISOLOC. This program
      provides the couch movements required to move the target to the isocentre and a
      micropositioner attached to the couch is used to make the adjustment. Beam films
      are repeated until the movements required are less than 1 mm in any direction. It
      is shown that the simple procedures of implanting the markers subcutaneously do
      not provide a stable reference system in about 25% of patients and the markers
      are now screwed into the cranium. The precision of the method is evaluated by
      phantom studies and measurements taken during several hundred treatments.

PMID- 8293261
TI  - Selection of anti-scatter grids for different imaging tasks: the advantage of low
      atomic number cover and interspace materials.
AB  - A Monte Carlo computer program has been developed for the study of anti-scatter
      grids used in diagnostic radiology. The program estimates the scatter from soft
      tissue phantoms representative of either adult or paediatric examinations and
      uses dose increase, signal-to-noise ratio improvement and contrast improvement
      factors to study grid performance. It has been used to quantify the advantage of
      replacing grids with aluminium covers and interspaces by grids using materials of
      low atomic number for these components. Two approaches are used. First, the
      aluminium and low atomic number alternatives are compared for five grid ratios at
      fixed strip density and width and for tube potentials of 50, 70, 100 and 150 kV.
      Second, 44 commercially available grids are compared for three different imaging
      situations (lumbar spine, chest and paediatric). The results demonstrate that
      grids made with carbon fibre cover and cotton fibre interspace result in greater
      improvements in contrast and signal-to-noise ratio, and lower dose increase
      factors, than do grids made with aluminium. The dose reduction varies with
      irradiation conditions and is generally larger at lower tube potentials, higher
      grid ratios and lower strip densities. A typical reduction in mean absorbed dose
      in the patient is 30% in an adult lumbar spine (AP view) at 70 kV with a grid
      with 36 strips per centimetre and ratio 12.

PMID- 8293262
TI  - Monte Carlo study of grid performance in diagnostic radiology: factors which
      affect the selection of tube potential and grid ratio.
AB  - A Monte Carlo computational model has been developed for the study of the
      performance of anti-scatter grids in diagnostic radiology. It is used here to
      estimate the scatter in the image plane from soft tissue phantoms (representing
      the patient) and to calculate image contrast and the mean absorbed dose in the
      phantom. Different scattering conditions, representative of various examinations,
      have been investigated: adult lumbar spine; small field radiography and
      fluoroscopy; adult chest and paediatric pelvis and chest. For each scattering
      condition, the combinations of tube potential and grid ratio have been found
      which, for a well designed grid, result in the lowest mean absorbed dose in the
      phantom for a fixed contrast level. In examinations which generate large amounts
      of scatter, the use of high grid ratios in combination with high tube potentials
      is favourable with regard to both mean absorbed dose in the phantom and tube
      charge. When less scatter is generated, either the grid ratio or the tube
      potential can be varied to achieve the desired contrast level. High grid ratios
      require shorter exposure times, but need careful alignment in the beam to prevent
      primary radiation cut-off. It is shown that the air gap technique can be used to
      reduce patient dose in examinations with small amounts of scatter, but in
      combinations with a lower tube potential than when a grid is used.

PMID- 8293263
TI  - Technical note: simultaneous multislice imaging with an additional slice gradient
      in the readout stage: an idea for multislice FLASH.

PMID- 8293264
TI  - Technical note: the development of quality assurance for Sheffield's radiotherapy
      treatment planning systems.
AB  - Quality assurance procedures have been defined and implemented for the treatment
      planning systems at Weston Park Hospital. The programme of tests and checks
      covers both hardware and software: hardware checks are concerned with the input
      and output performance of the system's peripheral devices; the software checks
      involve testing system data integrity, and testing the algorithms used for
      planning external photon and electron beams. Beam measurements from an ionization
      chamber scanned in water and air were compared with calculations from two
      independent treatment planning systems. Following the implementation of these
      quality assurance procedures, some improvements have been made to the system data
      used and changes have been introduced to planning practice.

PMID- 8293265
TI  - Case report: child abuse--necklace calcification--a sign of strangulation.
AB  - Strangulation has been postulated as one cause of cerebral hypoxia in child
      abuse. This report describes the finding of necklace calcification in an infant
      with rib fractures and a metaphyseal fracture and an admission of a shaking
      injury. The calcification is likely to represent fat necrosis as the result of
      strangulation.

PMID- 8293266
TI  - Case report: computed tomography of generalized lymphangiomatosis and
      chylothorax.
AB  - The diagnosis of lymphangiomatosis can often be made on clinical grounds with the
      aid of plain radiography. In children with intractable chylothorax computed
      tomography (CT) of the thorax may reveal the presence of a mediastinal mass but
      frequently in lymphangiomatosis will not demonstrate any specific features.
      Abdominal CT, on the other hand, may suggest the diagnosis by the association
      with intraabdominal lymphangioma.

PMID- 8293267
TI  - Case report: ossification of the thoracic ligamenta flava in a Caucasian: a rare
      cause of myelopathy.
AB  - Ossification of the ligamenta flava is rare and has been described almost
      exclusively in Japanese people. We present a case in which ossification of the
      thoracic ligamenta flava caused compressive myelopathy in a Caucasian.

PMID- 8293268
TI  - Case of the month: hypokalaemic hypertension: a real con!

PMID- 8293269
TI  - Short communication: is some of our radiation dosimetry wrong?

PMID- 8293270
TI  - Memorandum from the British Committee on Radiation Units and Measurements. Advice
      following ICRP publication 60.
AB  - In summary, it is recommended that: (i) The three operational quantities defined
      by ICRU, namely ambient dose equivalent, directional dose equivalent and personal
      dose equivalent, should be used for measurement in radiation protection. (ii) The
      values of these quantities should, for the present, be based on values of Q
      recommended in ICRP Publication 26 (ICRP, 1977). (iii) The values of organ
      weighting factors, wT, recommended in ICRP Publication 26 (ICRP, 1977) should,
      for the present, be retained. (iv) The operational quantities should not be
      modified to incorporate the values of Q recommended in ICRP Publication 60 (ICRP,
      1991) until it has been demonstrated that they are satisfactory indicators of the
      limiting quantities defined in ICRP 60. (v) Any changeover to the new values of
      the operational quantities should take place on a defined date.

PMID- 8293271
TI  - Latent image fading in mobile mammographic screening.

PMID- 8293272
TI  - Conscious visual perception without V1.
AB  - We used the technique of PET to determine whether visual signals reach visual
      area V5, specialized for visual motion, when a human patient, blinded by a lesion
      in area V1, discriminates the direction of motion of visual stimuli and shows,
      through his verbal reports, that he is consciously aware of both the nature of
      the visual stimulus and its direction of motion. The results showed that area V5
      was active without a parallel activation of area V1, implying that the visual
      input can reach V5 without passing first through V1 and that such an input is
      sufficient for both the discrimination and the conscious awareness of the visual
      stimulus.

PMID- 8293273
TI  - Impaired visual motion perception in the contralateral hemifield following
      unilateral posterior cerebral lesions in humans.
AB  - Contrast thresholds for a number of tasks were measured in the contralateral and
      ipsilateral upper quadrants of the visual field (eccentricity = 10 degrees)
      before and after an occipito-parietal surgical resection, in one patient, carried
      out for intractable epilepsy. Postoperatively the contrast thresholds for
      discriminating the speed of movement of drifting sine-wave gratings were elevated
      by greater than a log unit in the contralateral field with little or no change in
      the detection thresholds for the same stimuli. Contrast thresholds for opposite
      direction-of-motion (DOM) discrimination of a contrast modulated (CMod) grating
      (a 'non-Fourier' motion stimulus) were also elevated by about a log unit in the
      contralateral hemifield but thresholds for DOM discrimination of a sine-wave
      (luminance modulated, LMod) grating were unaffected. Contrast thresholds for
      orientation discrimination of stationary gratings (a non-motion task) were
      unaffected. This general pattern of results was found in two other patients
      following lateral occipital surgical resections. Eight other patients with
      occipito-temporal (two cases), parietal (three cases) and medial occipital lobe
      lesions (three cases) showed no difference between the two hemifields on any of
      the tasks. Comparison of the location of the lesions leads to the conclusion that
      damage to the lateral occipital gyri is responsible for the pattern of visual
      deficit observed. Damage to an extra-striate visual area concerned with motion
      perception (the human homologue of primate V5-MT) may have occurred. There has
      been no previous description of impairment of motion perception localized to a
      hemifield in humans. The characteristics of the residual motion perception in
      these cases is described further in the accompanying article [Plant and Nakayama
      (1993), Brain, 116, 1337-1353].

PMID- 8293274
TI  - The characteristics of residual motion perception in the hemifield contralateral
      to lateral occipital lesions in humans.
AB  - Unilateral damage to the lateral occipital region in humans can give rise to
      impaired motion perception in the contralateral visual field [Plant et al.
      (1993), Brain, 116, 1303-1335]. We report the following characteristics of the
      residual vision. (i) Spatial acuity and spatial frequency discrimination are not
      affected. (ii) Contrast thresholds for direction-of-motion (DOM) discrimination
      of luminance modulated (LMod) sine-wave gratings is unaffected regardless of
      drift temporal frequency and the effect of spatial and temporal frequency on
      drifting/counterphase sensitivity ratios is normal (providing further evidence
      that cortical directionally selective mechanisms are intact). (iii) Contrast
      thresholds for DOM discrimination of contrast modulated (CMod) gratings are
      elevated by a log unit across a range of drift velocities. (iv) The residual
      motion perception shows neither a directional nor a naso-temporal asymmetry. (v)
      Weber fractions for velocity discrimination are shown in one patient in whom this
      measurement was carried out, to be elevated by around a factor of three but the
      functions relating velocity discrimination to stimulus contrast and to the
      velocity of the standard are parallel in the affected and unaffected hemifields.
      (vi) Weber fractions for temporal frequency discrimination using counterphase
      modulated gratings are also elevated. We conclude that the degraded motion
      perception is mediated by mechanisms which have similar contrast and temporal
      properties to those subserving normal motion perception. Mechanisms subserving
      DOM discrimination of LMod gratings may be spared because they are more widely
      distributed in extra-striate cortex than mechanisms subserving non-Fourier
      (second-order) motion perception or velocity discrimination. The anomaly
      resembles that described in some recent animal studies of impaired motion
      perception after extra-striate cortical damage.

PMID- 8293275
TI  - Longitudinal study of central motor conduction time following stroke. 1. Natural
      history of central motor conduction.
AB  - A 12 month longitudinal study has been performed on 118 subjects following first
      ever stroke to determine changes in central motor conduction time (CMCT) to upper
      limb muscles. The responses to electromagnetic stimulation of the motor cortex
      and cervical motor roots were recorded bilaterally in the surface electromyograms
      of pectoralis major, biceps and triceps brachii and thenar muscles. The CMCTs
      obtained from these recordings in stroke patients have been compared with those
      obtained in 53 normal healthy subjects of a similar age. The first measurements
      were made within the immediate post-stroke period (12-72 h of the onset of
      symptoms) and repeated at set time intervals over 12 months. The first assessment
      of CMCT identified three groups: those with normal responses, delayed responses
      and absent responses. During the first 12 months following stroke various changes
      in CMCT occurred. Central motor conduction time may remain unchanged, delayed
      CMCT may return to normal and previously absent responses may reappear and be
      delayed or normal. Using electromagnetic stimulation of the motor cortex the
      thresholds for motor evoked responses in the different muscles were initially
      high and fell over 12 months.

PMID- 8293276
TI  - Longitudinal study of central motor conduction time following stroke. 2. Central
      motor conduction measured within 72 h after stroke as a predictor of functional
      outcome at 12 months.
AB  - A longitudinal study was performed on 118 first-ever stroke patients to evaluate
      neurophysiological measurements of central motor conduction time (CMCT) in the
      period immediately following stroke as predictors of functional outcome and
      mortality at 12 months. Measurements of CMCT were made as described in the
      accompanying article (Heald et al., 1993, Brain, 116, 1355-1370), in which the
      following three groups of patients were recognized within 12-72 h after the onset
      of symptoms: normal response group, delayed response group and no response group.
      Neurophysiological and clinical investigations were commenced 12-72 h (designated
      as day 1) after the onset of symptoms and repeated at set time intervals up to 12
      months. The subjects were examined neurologically and assessed using the
      Motricity Index for muscle strength, the Nine-hole Peg Test to measure manual
      dexterity, the Barthel Score for activities of daily living and the modified
      Rankin Scale for functional outcome. The duration of stay in hospital and the
      occurrence of stroke-related death were noted. During the first week following
      stroke, absence of responses correlated closely with the patient's symptoms and
      neurological observations of abnormal muscle tone and tendon reflexes.
      Correlations were made in the three groups of patients of functional scores at
      day 1 and at 12 months. Patients with normal CMCT had consistently higher scores
      throughout the 12 month period and achieved significantly better functional
      recovery. Patients with no responses showed poor performance in neurological and
      functional tests throughout the 12 month period. Patients with delayed CMCT had
      neurological and functional scores intermediate between those of the other two
      groups, but outcome at 12 months was similar to those in the normal response
      group. Where the threshold to cortical stimulation was abnormally high,
      functional outcome was generally poor. Mortality was highest in the group with
      absent responses and the survivors spent the longest period in hospital. In
      conclusion, the observation of normal or delayed CMCT at day 1 identifies a group
      of patients with a high probability of survival and functional recovery. The
      absence of responses to cortical stimulation at day 1 identifies a group of
      patients who are at high risk of poor functional recovery at 12 months and
      greater probability of stroke-related death during this period.

PMID- 8293277
TI  - Both primary motor cortex and supplementary motor area play an important role in
      complex finger movement.
AB  - In order to clarify the roles played by the primary motor cortex and the
      supplementary motor area in the execution of complex sequential and simple
      repetitive finger movements, regional cerebral blood flow (rCBF) was measured
      with PET using 15O-labelled water in five normal subjects. The PET data of each
      individual subject co-registered to his own MRI, was analysed. Compared with the
      resting condition, the mean rCBF was markedly increased in the contralateral
      sensorimotor cortex (M1-S1) and moderately increased in the contralateral
      cingulate gyrus and putamen in both the simple and complex motor tasks. During
      the complex motor task, in addition to the above, the mean rCBF was markedly
      increased in the supplementary motor area and the contralateral premotor area,
      and moderately increased in the ipsilateral M1-S1 and cerebellum. In the
      supplementary motor area, there was a moderate rCBF increase also during the
      simple task. However, comparison of the mean rCBF increase against the resting
      condition between the two tasks revealed a greater increase during the complex
      task than in the other only in the supplementary motor area and the ipsilateral
      M1-S1. Thus, in agreement with our previous electrophysiological findings, not
      only the supplementary motor area but also the M1-S1 seems to play an important
      role in the execution of complex sequential finger movements.

PMID- 8293278
TI  - The relationship between abnormalities of cognitive function and cerebral
      activation in amyotrophic lateral sclerosis. A neuropsychological and positron
      emission tomography study.
AB  - Neuropsychological assessment of 16 clinically non-demented patients with
      amyotrophic lateral sclerosis (ALS) and 16 age-matched controls revealed
      significantly (P < 0.05) impaired verbal fluency and picture recall in the ALS
      patients. On the basis of their verbal fluency scores, two subgroups of the ALS
      patients (five high, five low scores) and a different group of five age-matched
      controls then underwent positron emission tomographic (PET) measurement of
      regional cerebral blood flow (rCBF). Scans were performed in the resting state
      and while subjects performed stereotyped or freely selected movements of a
      joystick with their right hand. The pattern of cerebral activation associated
      with self-generated activity was determined by comparing the profile of rCBF
      during freely selected and stereotyped joystick movements. Statistical parametric
      mapping was used to determine significant differences in rCBF between the groups
      at rest and during activation. Regional cerebral blood flow at rest was
      significantly (P < 0.01) reduced in the anterior cingulate cortex of both ALS
      subgroups in comparison with controls. The profile of cortical and subcortical
      activation during performance of freely selected joystick movements relative to
      stereotyped movements was abnormal in ALS patients: (i) ALS patients with a
      normal fluency score showed significantly (P < 0.01) attenuated rCBF responses in
      comparison with controls in the left medial prefrontal cortex (Brodmann area 10)
      and the right and left parahippocampal gyri; (ii) ALS patients with impaired
      verbal fluency showed significantly (P < 0.01) attenuated rCBF responses in
      comparison with controls in the right and left medial prefrontal cortex (areas 9
      and 10), the rostral aspects of the right anterior cingulate cortex (areas 24 and
      32), the right parahippocampal gyrus and the anterior thalamic nuclear complex;
      (iii) ALS patients with impaired verbal fluency showed significantly (P < 0.01)
      attenuated rCBF responses in comparison with patients with normal verbal fluency
      in the right parahippocampal gyrus, the anterior thalamic nuclear complex and the
      rostral anterior cingulate cortex (area 24). Regional cerebral blood flow at rest
      in the right parahippocampal gyrus of ALS patients was significantly correlated
      with verbal fluency score (P = 0.01) and picture recall score (P = 0.01).
      Activation of the anterior thalamic nuclear complex in ALS patients was also
      significantly correlated with verbal fluency score (P = 0.001) and picture recall
      score (P = 0.01). The results show that abnormalities of function are present in
      regions along a limbo-thalamo-cortical pathway in some ALS patients during
      performance of a self-generated motor task.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8293279
TI  - A mechanism of quinolinic acid formation by brain in inflammatory neurological
      disease. Attenuation of synthesis from L-tryptophan by 6-chlorotryptophan and 4
      chloro-3-hydroxyanthranilate.
AB  - Quinolinic acid (QUIN), kynurenic acid (KYNA) and L-kynurenine (L-KYN) are
      neuroactive kynurenine pathway metabolites that accumulate in inflammatory
      neurological diseases. These increases were attributed to the induction of
      indoleamine-2,3-dioxygenase (IDO), the enzyme that converts L-tryptophan into L
      KYN. Direct conversion of L-tryptophan into QUIN by brain tissue occurs in
      conditions of CNS inflammation, but not by normal brain tissue. To investigate
      whether increased activity of enzymes distal to IDO may determine L-KYN
      conversion to QUIN, rhesus macaques were inoculated with poliovirus directly into
      the spinal cord, as a model of focal inflammatory neurological disease (FASEB J.
      6, 2977-2989, 1992). Induction of spinal cord IDO (35.9-fold) accompanied
      smaller, but proportional increases in kynurenine-3-hydroxylase (2.4-fold) and
      kynureninase (2.3-fold) activities, which were correlated to CSF and tissue QUIN
      levels, as well as to measures of inflammatory lesions. 3-Hydroxyanthranilate-3,4
      dioxygenase activity was unchanged. Cerebrospinal fluid KYNA levels increased in
      proportion to both IDO activity and L-KYN accumulation, though kynurenine
      aminotransferase activity was unaffected. Cerebrospinal fluid neopterin, a marker
      of macrophage and immune activation, accumulated in proportion to the responsive
      enzymes and metabolites. The cell types involved in producing QUIN were
      investigated in vitro. Human foetal brain cultures consisting of astrocytes and
      neurons converted large quantities of [13C6]L-tryptophan into L-KYN when
      stimulated by gamma-interferon, but very little [13C6]QUIN was formed unless
      macrophages (THP-1 cells) were first added to the cultures (to model a key
      component of brain inflammation). [13C6]L-Tryptophan was converted into
      [13C6]QUIN by either gamma-interferon stimulated macrophages, or following
      intracisternal administration into poliovirus-infected macaques. Inhibitors of
      the kynurenine pathway, 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilic
      acid, attenuated [13C6]QUIN formation by macrophages, and when co-infused with
      [13C6]L-tryptophan into poliovirus-infected macaques. These results suggest roles
      for increased activities of IDO, kynurenine-3-hydroxylase and kynureninase in
      accelerating the synthesis of QUIN, L-KYN and KYNA in conditions of brain
      inflammation. Macrophage infiltrates, and perhaps microglia, are important
      sources of QUIN, whereas constitutive brain cells and macrophages are sources of
      L-KYN. Drugs that inhibit kynurenine pathway enzymes attenuate QUIN formation in
      the CNS, and provide tools to examine the consequences of reduced QUIN
      accumulation.

PMID- 8293280
TI  - Electron transfer complexes I and IV of platelets are abnormal in Parkinson's
      disease but normal in Parkinson-plus syndromes.
AB  - Using a technique which requires only 100 ml blood we investigated the electron
      transfer complexes (ETC) I, III and IV in platelet mitochondria of 44 control
      subjects, 27 patients with idiopathic Parkinson's disease and eight patients with
      Parkinson-plus syndromes due to multiple system atrophy. In both control subjects
      and patients, ETC measurements were repeated at intervals of several months. The
      activities varied considerably among normal subjects, but intra-individual
      variation of ETC activities were low at repetitive measurements. In normal
      subjects there was no correlation between enzyme activities and age or training
      state. There was no difference in enzyme activities between smokers and non
      smokers in the control group. Complex I activity was lower in Parkinson's disease
      patients than in controls (14 versus 29 nmol/min/mg platelet protein; P < 0.001).
      Furthermore, the group difference in complex IV activity also reached statistical
      significance (83 versus 58 nmol/min/mg platelet protein; P < 0.001).
      Additionally, in some Parkinson's disease patients, activities of complex III
      were low and lay outside the control range, but the group difference did not
      reach significance. There was no correlation between complex I activity and
      disease duration or severity as well as the daily L-dopa dose in Parkinson's
      disease patients. Repeated measurements in five Parkinson's disease patients in
      the earliest stages of their illness demonstrated that the decrease in complex I
      and IV activities can develop rapidly within 1 year. In Parkinson-plus patients
      suffering from multiple system atrophy the ETC activities were normal.

PMID- 8293281
TI  - Nucleolar organizer regions in optic gliomas.
AB  - The biological nature of optic gliomas is controversial, with some considering
      them benign hamartomatous lesions, and others believing them to be true
      neoplasms. We evaluated the use of colloid silver impregnation of nucleolar
      organizer region-associated proteins (AgNORs) in making this distinction. Thirty
      one optic gliomas, 14 optic nerve meningiomas, and a single case of giant cell
      glioblastoma multiforme (monstrocellular glioma) of the optic chiasm were stained
      for AgNORs and counted in a masked fashion. The optic gliomas contained 2.01 +/-
      0.09 AgNORs per nucleus, similar to that of optic nerve meningiomas (2.15 +/-
      0.15) and our previously reported counts for diffuse fibrillary astrocytoma (2.22
      +/- 0.10), and significantly more than that of reactive astrocytosis (1.18 +/-
      0.02). Six of the seven optic gliomas examined had compound AgNORs, a feature
      associated with malignancy in other tumour types. AgNOR counts did not correlate
      with clinical features, including those seen during the post-operation course.
      These data suggest that optic gliomas may be true neoplasms, and not benign
      hamartomas.

PMID- 8293282
TI  - Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance
      of tactile allodynia?
AB  - Under normal conditions acute stimulation and sensitization of polymodal
      nociceptive C-fibres cause pain and, due to afferent axon reflex activation, a
      local skin vasodilatation, flare reaction and skin temperature increase. Two
      questions arise: (i) Do sensitized C-nociceptors signal allodynia in chronic
      postherpetic neuralgia? (ii) If not, does ongoing peripheral nociceptive C-fibre
      input maintain a central process that accounts for allodynia? Ten patients with
      postherpetic neuralgia and tactile allodynia and 10 control subjects were studied
      using a laser Doppler perfusion monitor. Peripheral nociceptive C-fibre function
      was assessed by quantitative measurement of the axon reflex vasodilatation and
      flare reaction induced by histamine iontophoresis and compared with non-neural
      vasodilatation induced by local skin heating. Resting skin temperature, skin
      resistance and resting skin blood flow were the same in the allodynic area and
      the contralateral homologous skin area. The histamine responses (vasodilatation
      and flare) were significantly reduced or nearly abolished in the allodynic area
      compared with the contralateral side, whereas the temperature-dependent
      vasodilatation in patients and the histamine responses in healthy controls showed
      no side differences. C-fibre mediated pain and itch sensations were also
      decreased in the allodynic area. These findings indicate a considerable
      impairment of cutaneous nociceptive C-fibre function in the allodynic area.
      Allodynic stimuli of 20 s did not cause any local blood flow change. Impairment
      of C-fibre function was positively correlated with intensity of neuropathic pain.
      We conclude that sensitized nociceptive C-fibres are not involved in signalling
      allodynia. Changes in CNS processing may occur after zoster infection that
      strengthen the synaptic ties between central pain signalling pathways and low
      threshold mechanoreceptors with A beta-fibres. This altered central processing is
      not maintained by ongoing cutaneous nociceptive C-fibre input, at least in some
      patients with postherpetic neuralgia. On the contrary, an anatomical synaptic
      reorganization depending on afferent C-fibre degeneration seems to be more
      likely, particularly in advanced stages of postherpetic neuralgia.

PMID- 8293283
TI  - Phenotypic variability in autosomal dominant cerebellar ataxia type I is
      unrelated to genetic heterogeneity.
AB  - Families with autosomal dominant cerebellar ataxia (ADCA), a heterogeneous group
      of diseases, were investigated prior to and during genetic linkage analysis. We
      report here on the clinical features of 122 affected individuals from 36
      unrelated families with ADCA type I, the most common type. Our results indicate
      an anticipation expressed in a mean 9.4 year earlier age at onset and more rapid
      clinical progression in successive generations. There was no imprinting, since
      age at onset, disease duration and severity of the disease were independent of
      parental transmission. Progressive cerebellar ataxia was variably associated with
      signs such as ophthalmoplegia, dysphagia, sphincter disturbances, briskness or
      loss of tendon reflexes, decreased vibration sense and amyotrophy, a variability
      correlated with disease duration. Linkage analysis of 10 informative families
      with microsatellite markers, located on the short arm of the chromosome 6,
      allowed the identification of four families showing positive linkage to the SCA1
      (spinal cerebellar ataxia 1) locus and six non-SCA1 families for whom linkage to
      this locus was excluded. This reflects non-allelic genetic heterogeneity. Thus,
      the analysis of clinical signs associated with cerebellar ataxia in SCA1 versus
      non-SCA1 kindreds did not distinguish between the two groups. The clinical
      picture of ADCA type I did not reflect the genetic heterogeneity of the disease.

PMID- 8293284
TI  - The case of aphasia or neglect after striatocapsular infarction.
AB  - The occurrence of aphasia or neglect was related to anatomo-structural (CT/MRI),
      functional [regional cerebral blood flow (rCBF)] and pathogenetic features
      [duration of middle cerebral artery (MCA) occlusion and degree of cortical
      leptomeningeal anastomoses] in 57 cases (26 with and 31 without aphasia or
      neglect) with strictly subcortical infarcts of one defined type, i.e.
      striatocapsular infarcts. No distinct pattern of language disturbances was found.
      Aphasic syndromes did not differ in the amount of involvement of the putamen,
      pallidum, head of caudate nucleus and white matter. Patients with aphasia or
      neglect had larger infarcts than those without. However, there was no specific
      involvement of the basal ganglia, the internal capsule or the deep white matter
      in patients with aphasia or neglect. Patients with aphasia or neglect had a
      significantly longer duration of MCA occlusion and mostly poor leptomeningeal
      collaterals. The cortical rCBF was significantly decreased in the cortical MCA
      territory in the patients with aphasia or neglect only. The rCBF remained low at
      follow-up after 1 year and corresponded to focal cortical atrophy on MRI,
      although neglect had subsided completely in all patients and aphasia had improved
      considerably in almost 75% of the cases. Aphasia or neglect after striatocapsular
      infarcts are most likely due to selective neuronal loss of the cerebral cortex
      due to prolonged MCA occlusion and insufficient collateral blood flow. Individual
      differences in recovery from aphasia after striatocapsular infarction can be
      explained in terms of the number of surviving cortical neurons.

PMID- 8293285
TI  - To what extent can aphasic syndromes be localized?
AB  - Modern views on the representation of function in the cortex make it difficult to
      maintain the notion that specific subtypes of aphasia are associated with
      specific centres within the language area. We have conducted a retrospective
      study on 221 aphasic patients with one contiguous vascular lesion in the
      territory of the middle cerebral artery. The localization of CT lesions was
      established within a standardized grid model. Aphasiological data were based on
      one or more examinations with the Aachen Aphasia Test. Both sets of data were
      processed in a data- and methodbase system. No unequivocal association between
      type of aphasia and localization of lesion was found. In a smaller study,
      participation of basal ganglia and in particular of the head of the caudate
      nucleus in lesions producing aphasia was not confirmed. Concepts of the
      localization of a lesion in aphasia must account for changes in patterns of
      aphasic symptoms in the presence of a stable lesion and for the impact of the
      neurological condition that has produced the lesion.

PMID- 8293286
TI  - Severe frontal syndrome associated with infarcts of the left anterior cingulate
      gyrus and the head of the right caudate nucleus. A clinico-pathological case.
AB  - The clinicopathological findings in a patient who presented a severe frontal
      syndrome and who had ischaemic lesions in the left anterior cingulate gyrus and
      in the head of the right caudate nucleus are reported. The clinical features
      included complex disorders such as distractibility, docility, emotional
      unconcern, manual grasping, prehension and utilization behaviour, perseverations
      and anterograde amnesia. They are closely similar to those previously described
      in a patient with bilateral lesions involving the anterior cingulate gyri. These
      findings suggest that (i) in the presence of a lesion of the anterior cingulate
      gyrus on one side, a lesion of the head of the contralateral caudate nucleus may
      be equivalent to a lesion of the anterior cingulate gyrus, the anterior cingulate
      gyrus--caudate complex working as a single functional unit; (ii) the anterior
      cingulate gyri (and anterior cingulate gyrus--caudate complexes) play a crucial
      role in the expression of frontal lobe functions; (iii) they are necessary for
      sustained goal-oriented responses to (emotionally or not) discriminated stimuli.

PMID- 8293287
TI  - Pseudo-hypersomnia and pre-sleep behaviour with bilateral paramedian thalamic
      lesions.
AB  - The sleep/wake status of three patients with bilateral lesions involving the
      paramedian thalamic regions was investigated. Long-term monitoring with infrared
      video camera and polygraphy were performed. In spite of presenting a behavioural
      aspect of sleep with sleep posture, eyes closed and lack of activity for 15-17 h
      per day, these subjects did not develop the normal non-rapid eye movement (NREM)
      and rapid eye movement (REM) sleep states during the daytime. The EEG indicated
      presence of a mixture of low amplitude, irregular, diffuse theta and alpha range
      frequencies during hours associated with this 'sleep-like' behaviour. Multiple
      sleep latency tests performed some time after the acute insult gave varying
      results, but while stage 1 NREM sleep might have been noted for three to four
      epochs, other states of sleep never appeared. Patients were apathetic and
      'drowsy' but could develop sleep only during the normal circadian period for
      sleep, i.e. during the night. Even several years later, in one of the subjects in
      whom follow-up recordings were obtained, apathetic behaviour and sleep
      'posturing' were present during much of the day, even though the subject, if
      requested, could perform tasks adequately all day long. Subjects with such
      lesions do not present a 'hypersomnia' but a 'de-arousal' or 'subwakefulness'
      with inability to develop sleep outside the normal circadian boundaries for its
      appearance. However, these subjects, at least initially, also lacked full
      wakefulness. They have a behavioural impairment with a compulsive sleep posture
      and are left in the transition between wakefulness and sleep.

PMID- 8293288
TI  - Pathological left-handedness. Left-handedness correlatives in adult epileptics.
AB  - Factors associated with left-handedness were examined in a large sample of adults
      who suffered with epileptic seizures (n = 446) in an attempt to delineate the
      concept of pathological left-handedness. Three main pathological factors were
      found associated with left-handedness: (i) right-hemiparesis of early onset; (ii)
      cognitive deficit; (iii) evidence of left-hemisphere disease on clinical
      examination. Familial sinistrality was also associated with left-handedness,
      independently of the above-mentioned pathological factors. Results support a
      clear-cut distinction between normal and pathological left-handedness. This
      distinction seems presently important for the evaluation of the great number of
      anomalies proposed to be associated with left-handedness.

PMID- 8293289
TI  - An evaluation of the role of internal cues in the pathogenesis of parkinsonian
      hypokinesia.
AB  - Our animal studies suggest that the basal ganglia provide an internal non
      specific cue to trigger movement and imply that Parkinson's disease involves a
      deficiency in this cueing mechanism. Indeed parkinsonian patients typically rely
      upon external visual cues. To assess the effects of such non-specific cueing
      mechanisms on movement, we examined patients' utilization of a variety of
      auditory cues. Ten patients suffering from Parkinson's disease, and their matched
      controls, pressed buttons at a series of two-way choice points sequentially down
      a pathway, both when the latter remained illuminated throughout its length, and
      when it had to be followed from memory alone. In other experimental conditions,
      auditory cues were also provided, either contingent upon the previous response,
      at its initiation (a medium level of advance information) or at its completion (a
      low level of advance information), or as a series of regularly paced (non
      contingent) auditory cues (from a metronome). In addition to error data, we
      recorded down time (DT, time to initiate each next response) and movement time
      (MT, time to execute each next response). However, both DT and MT measurements
      showed that parkinsonian patients were enormously disadvantaged by the absence of
      external cues. While contingent auditory cues were of some help, the performance
      of patients with Parkinson's disease was dramatically improved by the provision
      of non-contingent auditory information. Moreover, parkinsonian patients, unlike
      controls, were greatly affected by the length of individual sub-movements,
      especially in the absence of external cues. When the pathway to be followed
      remained illuminated, sub-movement length had little effect. We conclude that for
      well-learnt, predictable sequences the basal ganglia provide a non-specific
      internal cue that is necessary for switching between one movement and the next in
      a movement sequence, and also for development of preparatory activity for each
      sub-movement in the sequence.

PMID- 8293290
TI  - Effects of chronic ethanol administration on acetylcholinesterase activity in the
      somatosensory cortex and basal forebrain of the rat.
AB  - A chronic diet of ethanol has detrimental effects on the cholinergic system in
      adult humans and rats. This study examined the effects of chronic exposure to
      dietary ethanol on the anatomical organization of true acetylcholinesterase
      (AChE) active elements in rat cerebral cortex. We focused on the somatosensory
      cortex because of its highly organized chemical and cellular structure. Following
      42 days of exposure to an ethanol diet (6.7% v/v), there were marked changes in
      the cortical plexus of AChE-positive fibers. The AChE-positive plexus in ethanol
      treated rats was reduced in all cortical layers, in comparison to age-matched
      pair-fed control and chow-fed rats. The most marked reduction was evident in
      layers II/III, IV, and VIa. Moreover, the density of AChE-positive cell bodies
      was significantly reduced in the cortices of ethanol-fed rats, particularly in
      the deep laminae. These alterations in the chemoarchitecture of somatosensory
      cortex occurred in the absence of changes in the cytoarchitectonic organization
      of neocortex. There was no detectable ethanol-induced change in the density of
      Cresyl violet-stained neurons either in the horizontal limb of the diagonal band
      of Broca or in the nucleus basalis. The density of AChE-positive neurons in the
      nucleus basalis, however, was significantly lower in ethanol-fed rats than in
      controls. Thus, it appears that a mere 6 weeks of ethanol exposure is sufficient
      to alter the cholinergic innervation of the cerebral cortex. These cortical
      alterations occur despite the lack of an ethanol-induced death of neurons in the
      basal forebrain. Such changes may contribute to the memory loss associated with
      alcohol dementia.

PMID- 8293291
TI  - Stress protein co-localization to autofluorescent astrocytic inclusions in situ
      and in cysteamine-treated glial cultures.
AB  - In the aging brain, a unique subpopulation of limbic and periventricular
      astrocytes accumulates red autofluorescent, peroxidase-positive cytoplasmic
      inclusions distinct from lipofuscin. Cysteamine (CSH) exposure rapidly induces
      identical inclusions in cultured, immature astroglia. CSH induces a cellular
      stress response prior to astrocyte granulation. To determine whether stress
      proteins are actual constituents of the autofluorescent granules, 12-week-old rat
      brain sections and CSH-treated astroglial cultures were immunostained with
      various anti-stress protein antibodies and evaluated by laser scanning confocal
      microscopy. We observed intense co-localization of heat shock protein (HSP) 27
      and ubiquitin (Ub) to the autofluorescent astrocyte granules in situ and in CSH
      treated glial cultures. In both preparations, glucose regulated protein (GRP) 94
      consistently exhibited partial co-localization to the granule periphery and
      adjacent cytoplasm. In contrast, HSP72 co-localization to these inclusions was
      only occasionally seen and the granules appeared entirely devoid of HSP90 and
      alpha B-crystallin. Acute exposure of cultured astroglia to CSH induced intense
      cytoplasmic Ub staining, suggesting that activation of the Ub pathway may be an
      early event in the biogenesis of these astrocytic granules. Taken together, our
      results support the notion that the autofluorescent astrocyte inclusions are
      stress or heat shock granules which progressively accumulate in the aging
      periventricular brain. Moreover, CSH greatly accelerates the appearance of this
      senescent astrocyte phenotype in primary culture.

PMID- 8293292
TI  - Effects of submicromolar concentrations of dopamine on photoreceptor to
      horizontal cell communication.
AB  - Dopamine has been postulated to act as an intraretinal messenger for light
      adaptation by biasing retinal circuits to favor cone over rod inputs to second-
      and third-order neurons. As an experimental test, we studied the effects of
      dopamine and related ligands on rod to horizontal cell synaptic transfer. Rods
      and horizontal cells (HC) were recorded from simultaneously. Red and green light
      emitting diodes were modulated sinusoidally in counterphase at 1 Hz and their
      relative intensities adjusted to elicit a rod null. Dark-adapted HC's also showed
      a null, but exposure to 0.5-1.0 microM dopamine, which corresponds to the
      endogenous levels, elicited a large imbalance in the HC response while the rod
      null was maintained. Similar effects were achieved with either a D1 dopamine
      agonist, SKF 38393 (20 microM) or a D2 dopamine agonist, quinpirole HCl (1
      microM). Correspondingly, the frequency range over which the HC responded to red
      flickering lights increased very substantially. Exposure to a D2, but not a D1
      dopamine agonist increased rod flicker, but not as dramatically as in the HC.
      These data indicate that the synaptic gains of rod and cone transmission to a
      second order retinal neuron are modifiable by endogenous levels of dopamine.
      Secondly, the bandpass of rod flicker is altered by dopamine, acting through a D2
      dopamine receptor.

PMID- 8293293
TI  - Network analysis of functional auditory pathways mapped with fluorodeoxyglucose:
      associative effects of a tone conditioned as a Pavlovian excitor or inhibitor.
AB  - The purpose of this study was to examine how opposite learned associative
      properties of the same auditory stimulus are represented by the pattern of
      network interactions between auditory system structures. [14C(U)]2-fluoro-2
      deoxyglucose (FDG) autoradiography was used to compare mean auditory system
      activity and interregional correlations resulting from the presentation of a tone
      trained as either a Pavlovian conditioned excitor or inhibitor. Rats were trained
      with reinforced trials of the conditioned excitor (A+) intermixed with non
      reinforced trials of a tone-light compound (AX-). For the Conditioned Excitor
      group, the tone was the excitor (A+), while for the Conditioned Inhibitor group
      the tone was the inhibitor (X-). After conditioning, both groups were injected
      with FDG and presented with the same tone. Structural equation models,
      constructed from the anatomical connections between auditory regions and their
      interregional correlations in FDG uptake, were used to calculate path
      coefficients representing the network interactions. The opposite associative
      significance of the tone was reflected as functional changes in the interactions
      between parallel auditory pathways. Direct covariance effects through lemniscal
      pathways from the ventral cochlear nucleus were similar in absolute magnitude but
      differed in sign between the Excitor and Inhibitor network models. Extra-auditory
      influences on the dorsal cochlear nucleus were greater for the tone-inhibitor,
      reflecting possible interactions of this nucleus with extra-auditory regions. The
      different associative effects of the tone suggest that central auditory pathways
      can code not only the physical qualities, but also the associative significance
      of auditory stimuli. These findings demonstrate that neural network interactions
      differentiate the associative effects of tones in the brain. It is proposed that
      associative learning is a distributed property of neural networks and that such a
      property can be understood by considering the interactions between component
      parts of the network.

PMID- 8293294
TI  - Individual pineal cells exhibit a circadian rhythm in melatonin secretion.
AB  - Pineal glands and dissociated pineal cells exhibit a circadian rhythm of
      melatonin secretion in vitro which persists for several cycles under constant
      conditions. It is not known whether individual, physically isolated pineal cells
      are capable of generating a circadian oscillation in melatonin release. This
      question was addressed by utilizing a reverse hemolytic plaque assay for the
      detection of melatonin secretion from individual pineal cells. Dissociated pineal
      cells from the anole lizard, maintained in short term culture, displayed a marked
      variation in melatonin secretion for up to 72 h under both cyclic lighting
      conditions and in constant dark. The persistence of daily fluctuations of
      melatonin secretion from individual cells strongly suggests that individual
      pineal cells can function as circadian oscillators.

PMID- 8293295
TI  - Functional consequences of expression of the neuron-specific, protein kinase C
      substrate RC3 (neurogranin) in Xenopus oocytes.
AB  - RC3 (neurogranin) is a neuron-specific substrate of protein kinase C (PKC) that
      accumulates predominantly in dendritic spines of forebrain neurons and undergoes
      long-term potentiation (LTP)-associated increases in PKC-phosphorylation in
      hippocampal slices. Here the hypothesis that RC3 functions by modulating the
      IP3/DAG second messenger pathway after its phosphorylation by DAG-activated PKC
      was tested by heterologous expression in Xenopus oocytes. Acetylcholine-evoked
      inward chloride (Cl-) currents, dependent on both IP3 release and intracellular
      calcium (Ca2+), were 2- to 3-fold higher in RC3-injected oocytes than in
      uninjected control oocytes. RC3-oocytes did not exhibit enhanced currents when
      preincubated with the protein kinase inhibitor H-7 or when a glycine residue was
      substituted for serine, the PKC phosphorylation site of RC3. Activation of
      endogenous oocyte PKC by phorbol esters generated inward Cl- currents in RC3
      oocytes but not in control oocytes. RC3-dependent Cl- currents were also elicited
      by phorbol ester in Ca(2+)-free media. We propose that PKC-phosphorylated RC3 is
      capable of enhancing the mobilization of intracellular Ca2+ in Xenopus oocytes
      and, by inference, may play a role in Ca2+ homeostasis in dendrites of forebrain
      neurons.

PMID- 8293296
TI  - Modulation of carbachol responsiveness in rat CA1 pyramidal neurons by
      corticosteroid hormones.
AB  - Pyramidal neurons in the rat CA1 hippocampal area contain membrane receptors for
      acetylcholine but also intracellular receptors for the adrenal corticosteroid
      hormone corticosterone, i.e., mineralocorticoid receptors (MRs) and
      glucocorticoid receptors (GRs). In this in vitro study we investigated if
      occupation of MRs or GRs affects the responsiveness of CA1 pyramidal neurons to
      the cholinergic analogue carbachol. In slices from adrenally intact rats, where
      probably most of the MRs and a considerable degree of the GRs were occupied,
      carbachol (0.1-30 microM) induced a dose-dependent: (i) depolarization; (ii)
      reduction of the afterhyperpolarization and spike frequency accommodation
      associated with depolarizing current pulses; and (iii) reduction of the
      synaptically evoked EPSP, slow IPSP and (with higher doses) the fast IPSP. The
      carbachol responses in slices from adrenalectomized (ADX) rats, where both MRs
      and GRs are unoccupied, were generally similar to the responses in the adrenally
      intact controls. However, neurons recorded in slices from ADX rats 1-4 h after a
      brief (20 min) application of 3 nM aldosterone, thus predominantly occupying MRs,
      showed a significant reduction of the carbachol (1 microM) induced
      depolarization, when compared to the adrenally intact group. By contrast, neurons
      recorded in ADX slices treated with 30 nM corticosterone, inducing simultaneous
      activation of MRs and GRs, displayed significantly larger carbachol-evoked
      depolarizations (1 and 3 microM) than neurons in the three previous experimental
      groups. Carbachol-induced actions on the afterhyperpolarization, accommodation
      and synaptically evoked responses did not consistently depend on steroid receptor
      occupation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293297
TI  - Inositol treatment raises CSF inositol levels.
AB  - Inositol is a key precursor for synthesis of phosphatidylinositol in a major
      second messenger signalling system. It is biologically active in syndromes such
      as respiratory distress syndrome but has been thought to be excluded from CNS by
      the blood-brain barrier. Oral inositol treatment of 8 patients is shown to
      significantly increase CSF inositol by almost 70%, suggesting possible CNS
      therapeutic applications of this compound and possible CNS side-effects of
      systemic therapy.

PMID- 8293298
TI  - GABA receptors in the region of the dorsomedial hypothalamus of rats regulate
      anxiety in the elevated plus-maze test. II. Physiological measures.
AB  - In the previous report, we had shown that blockade and enhancement of GABAA
      receptors in the DMH of rats increased or decreased the level of anxiety,
      respectively, as measured by the elevated plus-maze test. The present study was
      conducted to assess the effects of enhancing GABAA neurotransmission in the DMH
      of rats on the physiological concomitants of anxiety such as increases in heart
      rate (HR), blood pressure (BP) and plasma norepinephrine (NE) levels while the
      animals were placed on the elevated plus-maze. Male Sprague-Dawley rats were
      equipped with arterial and venous catheters and stereotaxically implanted with
      microinjection cannulae in the cardiostimulatory region of the DMH where
      injection of bicuculline methiodide (BMI) elicited increases in heart rate under
      anesthesia. After recovery, rats were injected with either saline or the GABAA
      agonist muscimol and their HR, BP and plasma NE responses were measured when
      confined in the open or the closed arm of the elevated plus-maze. Injection of
      muscimol into the DMH reduced the increases seen in HR, BP and plasma NE when the
      rats were confined to either the closed or the open arms in addition to
      decreasing 'anxiety' in the plus-maze. Injection of muscimol into the areas of
      the hypothalamus surrounding the DMH did not significantly affect the changes in
      HR, BP and plasma NE in the plus-maze. Blocking the changes in HR and BP elicited
      by microinjecting GABAergic drugs into the DMH of rats, with systemic injections
      of a combination of atropine and the beta-blocker atenolol, did not block the
      behavioral effects of the GABAergic drugs in the plus-maze test.

PMID- 8293299
TI  - A CRF antagonist attenuates stress-induced increases in NA turnover in extended
      brain regions in rats.
AB  - We investigated the effects of intracerebroventricular (i.c.v.) administration of
      corticotropin-releasing factor (CRF) antagonist, alpha-helical CRF9-41 (ahCRF),
      on increases in noradrenaline (NA) turnover caused by immobilization stress in
      rat brain regions. Pretreatment with ahCRF (50 or 100 micrograms) significantly
      attenuated increases in levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate
      (MHPG-SO4), the major metabolite of NA in rat brain, in the locus coeruleus (LC)
      region, and attenuated the MHPG-SO4/NA ratio after immobilization stress for 50
      min in the cerebral cortex, hippocampus, amygdala, midbrain and hypothalamus.
      However, stress-induced increases in plasma corticosterone levels were not
      decreased significantly by pretreatment with ahCRF. These results suggest that
      CRF, released during stress, causes increases in NA release in extended brain
      regions of stressed rats.

PMID- 8293300
TI  - Sexual dimorphism in the trigeminal motor neurons innervating the mouse masseter
      muscle.
AB  - The extrafusal and intrafusal muscle fibers in the masseter muscle are innervated
      by motoneurons in the trigeminal motor nucleus (Mo 5). In the present study, we
      found that the number of trigeminal motor neurons in the male mouse was
      significantly larger than that in the female. However, we could not detect any
      significant difference between male and female mice in the number of sensory
      neurons in the trigeminal mesencephalic nucleus (Me 5). This is the first report
      on sexual dimorphism in masticatory motoneurons of mammals.

PMID- 8293301
TI  - The use of the optical disector to estimate the number of neurons, glial and
      endothelial cells in the spinal cord of the mouse--with a comparative note on the
      rat spinal cord.
AB  - By means of stereological techniques such as the optical disector, the total
      number of cells in the spinal cords of five albino mice were estimated. The mean
      number of cells in the gray and the white matter was 9.0 and 4.1 million,
      respectively. Of the cells in the gray matter, 4.0 million were classified as
      neurons, 2.8 million as glial and 1.7 million as endothelial cells whereas 0.4
      million remained unclassified. Of the neurons in the gray matter, 1.2 million
      were located in the cervical region, 1.4 million in the thoracic region, 0.9
      million in the lumbar region and 0.4 million in the sacro-coccygeal region. The
      gray matter in the spinal cord of the mouse contained relatively more neurons and
      less glial cells than the gray matter in the rat spinal cord. The fraction of
      cells in the cervical, thoracic, lumbar and sacro-coccygeal part of the cord
      were, however, quite similar in the two species. In both species the number of
      neurons in the ventral horns made up about 8-9% of the total neuron population in
      the gray matter of the cord.

PMID- 8293302
TI  - Caffeine- and muscarinic receptor agonist-sensitive Ca2+ stores in chick ciliary
      ganglion cells.
AB  - To investigate the presence and the role of intracellular Ca2+ stores in chick
      ciliary ganglion cells, the concentration of cytosolic free Ca2+ ([Ca]in) was
      measured in acutely isolated neurons, using fura-2 microfluorometry. Caffeine
      caused a substantial increase in [Ca]in following or during high K+
      depolarization; this response was inhibited by treatment of the cells with
      thapsigargin or with caffeine plus ryanodine. The peak value and the rate of the
      depolarization-induced [Ca]in increase were not much altered by either of these
      treatments, which deplete caffeine-sensitive Ca2+ stores. The muscarinic receptor
      agonists muscarine, oxotremorine M, and methacholine, caused substantial
      increases in [Ca]in, in a manner that was partially dependent on Ca2+. These
      agonists also caused a rise in [Ca]in during K+ depolarization, which rise was
      inhibited by treatment with thapsigargin or with caffeine plus ryanodine. The
      response to oxotremorine M during depolarization was strongly inhibited by 10 nM
      4-DAMP, but was not inhibited by 1 microM pirenzepine or by 1 microM AF-DX 116.
      These results indicate that chick ciliary ganglion cells possess Ca2+ stores that
      are activated by both caffeine and a second messenger generated by the activation
      of the M3 muscarinic receptor subtype.

PMID- 8293303
TI  - Diurnal variations of serotonin and dopamine levels in discrete brain regions of
      Syrian hamsters and their modification by chronic clorgyline treatment.
AB  - In Syrian hamsters, chronic administration of the type A monoamine oxidase
      inhibitor, clorgyline (CLG), alters the intrinsic period and daily pattern of the
      circadian rhythm of wheel running, and changes the intensity-response curve for
      phase-shifting of the rhythm by light pulses. Chronic treatment with CLG also
      decreases hypothalamic and peritoneal temperatures, particularly during the rest
      phase of the activity-rest cycle. To help identify monoamines that may mediate
      CLG's effects on circadian rhythms, we measured levels of dopamine (DA) and
      serotonin (5-HT) at nine time points over a 24-h period in micro-dissected brain
      regions in chronic CLG-treated or saline-treated hamsters. For 5-HT, a diurnal
      variation was detected in all regions in saline-treated animals; for DA, no
      diurnal variation was detected in any region. In all regions, 5-HT levels and, to
      a lesser extent, DA levels were higher after CLG treatment. The acrophase of the
      5-HT rhythm in the suprachiasmatic nucleus (SCN) was delayed by CLG-treatment,
      while the acrophase in the dorsal raphe nucleus was unchanged. The diurnal
      variation of 5-HT in the paraventricular nucleus of the hypothalamus, medial
      preoptic area, and median raphe nuclei was no longer detectable after chronic CLG
      treatment. The phase-delay induced by CLG treatment in the daily rhythm of
      serotonin levels in the SCN, which functions as a circadian pacemaker, may be an
      important mechanism underlying the drug's capacity to slow the intrinsic rhythm
      of the pacemaker and to phase-delay behavioral rhythms that are under its
      control.

PMID- 8293304
TI  - 5-HT2 receptor immunoreactivity on cholinergic neurons of the pontomesencephalic
      tegmentum shown by double immunofluorescence.
AB  - The serotonin-2 (5-HT2) receptor subtype is implicated in several behavioral and
      physiological processes, and may be the site of action of hallucinogens and
      certain psychotherapeutic drugs. To better understand the function and regulation
      of 5-HT2 receptors, it is necessary to determine the specific brain regions and
      cell types expressing them. By double immunofluorescence using a polyclonal
      antibody raised against the rat 5-HT2 receptor in conjunction with an antibody
      against choline acetyltransferase (ChAT), the synthetic enzyme for acetylcholine,
      we have shown that cholinergic neurons in the rat laterodorsal and
      pedunculopontine tegmental nuclei express 5-HT2 receptors. In contrast, there was
      little co-localization of 5-HT2 and ChAT immunoreactivity in neurons of the basal
      forebrain or striatum, even though the 5-HT2- and ChAT-positive cells in these
      regions overlapped extensively. These findings are discussed in relation to the
      potential interaction between cholinergic and serotonergic systems in sleep
      regulation, hallucinogenesis and the pathophysiology of neuropsychiatric
      disorders.

PMID- 8293305
TI  - Repeated NMDA receptor activation induces distinct intracellular calcium changes
      in subpopulations of striatal neurons in vitro.
AB  - The mechanisms underlying long-term calcium changes evoked by excitatory amino
      acids have not been previously examined in striatal neurons. Fura-2 fluorescence
      measurements were used to examine intracellular calcium concentration ([Ca2+]i)
      changes due to repeated N-methyl-D-aspartate (NMDA) receptor activation, in
      primary cultures of murine striatal neurons. Three applications of 200 microM
      NMDA (for 2 min, each application separated by 7 min), in 0 magnesium-containing
      artificial cerebral spinal fluid, elicited three distinct responses. In 50 +/- 8%
      of the NMDA-responsive neurons, no persistent increases in [Ca2+]i (final [Ca2+]i
      < or = 150% baseline) were observed, while in 33 +/- 7% and 17 +/- 3% of the
      cells, sustained (peak response > final [Ca2+]i > 150% baseline) and uncontrolled
      increases (final [Ca2+]i > or = peak response) were observed, respectively. NMDA
      responsive neurons that were intensely immunoreactive for the calcium binding
      protein calbindin-D28k never exhibited uncontrolled increases in [Ca2+]i. Removal
      of extracellular Ca2+ significantly attenuated sustained, but not uncontrolled,
      increases in [Ca2+]i; sustained increases in some neurons were also attenuated by
      application of verapamil (100 microM) or MK-801 (1 microM). Pre-treatment of
      striatal neurons with the protein kinase C blocker sphingosine (20 microM),
      virtually eliminated the development of sustained or uncontrolled increases in
      [Ca2+]i. These findings suggest that specific intracellular mechanisms regulate
      the distinct [Ca2+]i responses of subpopulations of striatal neurons to repeated
      NMDA receptor activation.

PMID- 8293306
TI  - Interaction of cholinergic-dopaminergic systems in the regulation of memory
      storage in aversively motivated learning tasks.
AB  - These experiments examined the interaction between muscarinic cholinergic and
      dopaminergic systems in the modulation of memory storage. Male CD1 mice (25-30 g)
      were trained in an inhibitory avoidance (IA) and a Y-maze discrimination (YMD)
      task. The first experiment examined the dose-response effects, on retention, of
      agonists and antagonists specific for either D1- or D2-receptors. Immediately
      posttraining mice were given i.p. injections of saline, the D1-receptor agonists
      SKF 38393 (3.0, 10.0 or 30.0 mg/kg) or SKF 77434 (3.0, 10.0 or 30.0 mg/kg), the
      D1-receptor antagonist SCH 23390 (0.03, 0.1, or 1.0 mg/kg), the D2-receptor
      agonist quinpirole (0.3, 1.0 or 3.0 mg/kg) or the D2-receptor antagonist
      sulpiride (3.0, 10.0, 30.0 or 100.0 mg/kg). Retention was tested 48 h later. The
      drugs affecting D1-receptors did not affect retention. In contrast, in both tasks
      quinpirole enhanced retention and sulpiride impaired retention. In the IA task,
      quinpirole (3.0 mg/kg) blocked the retention impairing effects of the muscarinic
      cholinergic antagonist atropine (10.0 mg/kg), and sulpiride (3.0, 10.0, 30.0 or
      100.0 mg/kg) significantly attenuated the memory enhancing effects of the
      muscarinic cholinergic agonist oxotremorine (35.0 or 70.0 micrograms/kg). D1
      receptor agents did not modify the effects of either atropine or oxotremorine on
      retention of the IA response. These findings suggest that the effects of
      cholinergic muscarinic agents on retention of the IA response are mediated by
      influences involving D2-dopaminergic mechanisms. In the YMD task, atropine (10.0
      mg/kg) blocked the memory-enhancing effects of quinpirole (3.0 mg/kg) and
      oxotremorine (35.0 or 70.0 micrograms/kg) attenuated the memory impairing effect
      of sulpiride (3.0, 10.0, 30.0 or 100.0 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293307
TI  - Neuronal and behavioral correlates of intrastriatal infusions of amphetamine in
      freely moving rats.
AB  - When injected systemically in rats, amphetamine routinely activates striatal
      neurons that increase firing rate in close temporal association with movement but
      suppresses nonmotor-related neurons. To assess the role of striatal mechanisms in
      these opposing effects, D-amphetamine (20 micrograms/microliters) was infused (10
      microliters/h) directly into the striatum of awake, behaving rats and single-unit
      activity was recorded simultaneously at the infusion site. Intrastriatal
      amphetamine reliably activated motor-related, but suppressed nonmotor-related
      neuronal activity shortly after infusion onset. These changes in firing rate
      preceded overt behavioral changes, in most cases by several minutes. When they
      did emerge, behavioral responses were characterized mainly by focused sniffing
      and head bobbing. Interestingly, the strongest behavioral responses, as measured
      by onset latency and response magnitude, were likely to result from infusions
      into motor-related rather than nonmotor-related recording sites. Systemic
      injection of haloperidol (1.0 mg/kg) shortly after infusion offset suppressed
      both behavior and striatal neuronal activity. Control infusions of intrastriatal
      saline had no consistent effect on either striatal neuronal activity or behavior.
      Collectively, these results indicate that the divergence in firing rate between
      motor- and nonmotor-related striatal neurons reflects an intrinsic action of
      amphetamine in the striatum rather than a secondary effect of behavioral
      feedback. Moreover, the linkage of motor-related striatal areas with the
      strongest behavioral responses to amphetamine suggests important functional
      differences between motor- and nonmotor-related striatal neurons.

PMID- 8293308
TI  - GABA receptors in the region of the dorsomedial hypothalamus of rats regulate
      anxiety in the elevated plus-maze test. I. Behavioral measures.
AB  - Gamma-aminobutyric acid (GABA) receptor blockade in the region of the dorsomedial
      hypothalamus (DMH) elicits a constellation of responses including increases in
      heart rate, blood pressure, respiration, aversive behavioral responses and
      experimental anxiety as measured by the 'conflict' test. The aim of the present
      study was to assess the effects of enhancing and blocking GABA receptors in the
      DMH of rats placed on the elevated plus-maze test of anxiety. Male Sprague-Dawley
      rats were implanted with chronic microinjection cannulae in the DMH bilaterally
      at sites where injection of 50 pmol of the GABAA antagonist bicuculline
      methiodide (BMI) elicited an increase in heart rate of at least 50 beats/min
      under anesthesia. After recovery, the responses of these rats were tested on the
      elevated plus-maze following injections of saline, the GABAA agonist muscimol and
      the GABAA antagonists BMI and picrotoxin. Injection of muscimol caused a dose
      dependent 'anxiolytic-like' effect while both BMI and picrotoxin caused increases
      in the experimental anxiety on the elevated plus-maze. Microinjection of muscimol
      into other non-cardiostimulatory regions of the hypothalamus did not
      significantly affect the responding of rats on the plus-maze. These results
      support the hypothesis that GABAA receptors in a discrete cardiostimulatory
      region of the DMH regulate experimental anxiety in rats.

PMID- 8293309
TI  - Effects of organophosphates on rabbit pyramidal cells firing pattern and
      hippocampal theta rhythm.
AB  - The effects of the irreversible acetylcholinesterase (AChE) antagonist paraoxon
      (Px) on hippocampal neurophysiology were investigated and compared to those of
      physostigmine in urethane-anaesthetized rabbits. Hippocampal CA1 EEG signals were
      analyzed by power spectra. Following intracarotid administration, the two drugs
      induced a similar fundamental low-frequency theta power peak while the appearance
      of a second theta harmonic was commonly found under Px. Again, inhibition of CA1
      pyramidal cells firing was significantly more pronounced after Px injection than
      after physostigmine. A potent inhibitory action was also described following
      local Px iontophoretic application. However, a discrepancy appeared between the
      effects of Px and the classical cholinergic drugs (acetylcholine, physostigmine).
      The results indicate that Px and physostigmine have a rather similar influence on
      the septo-hippocampal pathway and support suggestions that Px could act within
      local hippocampal circuitry through other systems than the cholinergic system
      exclusively.

PMID- 8293310
TI  - Role of the medial septal area on the cardiovascular, fluid and electrolytic
      responses to angiotensin II and cholinergic activation into the subfornical organ
      in rats.
AB  - In the present study we investigated the effect of electrolytic lesion of the
      medial septal area (MSA) on the pressor and dipsogenic response to cholinergic
      activation and angiotensin II (ANGII) injection into the subfornical organ (SFO)
      in rats. In addition the effect of MSA lesion on the natriuresis, kaliuresis and
      diuresis after cholinergic activation of the SFO was also investigated. Sham- and
      MSA-lesioned rats with a stainless steel cannula implanted into the SFO was used.
      The injection of ANGII (12 ng) into the SFO in sham rats produced pressor (24 +/-
      2 mmHg) and dipsogenic (9.6 +/- 1.1 ml/h) responses. MSA lesion, both acute (2-6
      days) and chronic (15-19 days), reduced the pressor (14 +/- 2 mmHg) and
      dipsogenic (2.7 +/- 1 ml/h) responses to ANGII into SFO. The injection of the
      cholinergic agonist carbachol (2 nmol) into the SFO in sham rats produced pressor
      (48 +/- 4 mmHg), dipsogenic (10 +/- 1.2 ml/h), natriuretic (457 +/- 58 microEq/2
      h) and kaliuretic (249 +/- 16 microEq/2 h) responses. Acute, but not chronic MSA
      lesion reduced the pressor (27 +/- 3 mmHg), natriuretic (198 +/- 55 microEq/2 h)
      and kaliuretic (128 +/- 16 microEq/2 h) responses to carbachol into SFO. No
      change in the dipsogenic response to carbachol into the SFO was observed in MSA
      lesioned rats. Antidiuresis after carbachol was observed only in MSA-lesioned
      rats. The present results show that the MSA plays a role on the pressor,
      natriuretic and kaliuretic responses to cholinergic activation of the SFO in rats
      and on the pressor and dipsogenic responses to ANGII into the same area.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8293311
TI  - Prenatal oxazepam affects passive avoidance performance of preweaning mice.
AB  - CD-1 outbred mice were exposed to oxazepam on fetal days 12-16 by maternal
      administration (per os of 15 mg/kg twice daily at 8 a.m. and 8 p.m.) and fostered
      at birth to untreated dams, while control mice received vehicle solution. Mice
      were then tested on postnatal day 14 and 15 in a passive avoidance apparatus for
      their ability to withhold a step-down response from a vibrating platform. The
      step-down response was punished with a mild footshock. Each animal was subjected
      to a maximum of 15 trials. Mice prenatally treated with oxazepam showed an
      impairment in the acquisition of the task as indicated by shorter latencies to
      step-down throughout the 15 trials in both sessions (days 14 and 15). As control
      nonreinforced animals prenatally treated with oxazepam did not show a similar
      alteration in latency to step-down, these data suggest that prenatal exposure to
      oxazepam influences behavioral performance of preweaning mice in an aversively
      motivated task.

PMID- 8293312
TI  - Reversal of early phenobarbital-induced cholinergic and related behavioral
      deficits by neuronal grafting.
AB  - The present experiment was performed to assess the possible restoration of normal
      maze behavior, as well as parallel muscarinic receptor binding capabilities, in
      mice pre- or neonatally exposed to phenobarbital. Mice were exposed to
      phenobarbital prenatally by feeding the mother phenobarbital (3 gkg milled food)
      on gestation days 9-18 (PreB mice), or neonatally, by daily injections of 50
      mg/kg Na phenobarbital to the pups on days 2-21 (NeoB). At adulthood, PreB and
      NeoB mice were 61.3% and 65% deficient, respectively, in the hippocampus-related
      Morris maze behavior, as compared to control. Both groups had a 58% increase in
      their hippocampal muscarinic receptors maximal binding (Bmax) (p < 0.001); the
      dissociation constant (Kd) was not affected by the phenobarbital exposure.
      Treated animals and their respective controls received septal cholinergic
      embryonic graft into the hippocampus. The viability of the transplants was
      confirmed by AChE histochemistry. Nine weeks later the grafted mice showed
      significant improvement in the Morris maze (52% for both PreB and NeoB (p <
      0.001)). Their Bmax was also reduced from early phenobarbital exposed animals'
      levels by 15% for PreB and by 25% for NeoB (p < 0.001). The results suggest that
      early phenobarbital-induced behavioral deficit and their related biochemical
      alterations can be partially corrected by the appropriate neural grafting, and
      thus provide further support to the apparent relationship between the early
      phenobarbital-induced septohippocampal cholinergic alterations and the
      hippocampus-related behavioral deficits.

PMID- 8293313
TI  - Insulin and glucose-induced changes in feeding and medial hypothalamic monoamines
      revealed by microdialysis in rats.
AB  - Microdialysis from the ventromedian (VMH) and paraventricular (PVN) regions and
      simultaneous infusion of insulin alone (orexigenic) or with glucose
      (anorexigenic) was performed in the free-feeding rat. Intravenous insulin
      infusion (1 IU in 1 ml over 1 h) resulted in the expected glucoprivic feeding and
      a decrease in dopamine (DA) and serotonin (5-hydroxytryptamine [5-HT]) with an
      increase in their respective metabolites, dihydroxyphenylacetic acid (DOPAC) and
      5-hydroxyindolacetic acid (5-HIAA). These data are quite different from those
      observed in spontaneous ad lib feeding: increase in DA, 5-HT and 5-HIAA and
      decrease in DOPAC. These last changes were not superimposed on insulin effects
      when insulin-induced meals occurred. When food was not available, insulin
      infusion induced the same changes except an increase in DA levels which could
      probably be ascribed to stress. When insulin was infused together with a
      sufficient amount of glucose to prevent hypoglycemia, we observed the usual
      anorexigenic effect. Although this treatment had an effect on induced-feeding
      opposite to that following insulin alone, the changes in hypothalamic monoamines
      were similar. The only consistent overall change is finally the rise in 5-HIAA
      found in both spontaneous and induced feeding conditions. These data suggest that
      monoaminergic changes in the VMH and PVN are not directly implicated in the
      control of feeding but they rather reflect metabolic events that accompany this
      behavior.

PMID- 8293314
TI  - Semicarbazide-sensitive amine oxidase and monoamine oxidase in rat brain
      microvessels, meninges, retina and eye sclera.
AB  - Monoamine oxidase-A and -B (MAO-A and MAO-B) and semicarbazide-sensitive amine
      oxidase (SSAO) activities were assessed in several rat micro-vascular tissues and
      eyes using selective substrates and inhibitors. In rat brain microvessels both
      MAO-A and MAO-B activities are relatively high and the levels of the two types of
      MAO's are comparable. Retina possesses a similar ratio of MAO-A and B but the
      activities are much lower. Eye sclera and meninges exhibit mainly MAO-A and MAO
      B, respectively. Aorta is the only tissue where SSAO is the predominant amine
      oxidase. Relatively low, but significant amounts of SSAO were also detected in
      brain microvessels, meninges, retina and eye sclera. Methylamine was observed to
      be deaminated by SSAO from different tissues. The physiological and toxicological
      implications of amine oxidases in these tissues are discussed.

PMID- 8293315
TI  - Effects of alpha-tocopherol on lipid peroxidation and mitochondrial reduction of
      tetraphenyl tetrazolium in the rat brain.
AB  - The antioxidant effect of alpha-tocopherol was assessed in a model of ischemia
      reperfusion in the rat brain. In this model, permanent ischemia of the cortical
      branches of the middle cerebral artery was combined with bilateral occlusion of
      the common carotid arteries for 1 h and restoration of circulation for a period
      of 2 h. Lipid peroxidation and mitochondrial reduction of tetraphenyl tetrazolium
      (TPT) were determined in both untreated and d-alpha-tocopherol treated rats.
      Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation
      via the formation of hydroxyl anions. Malondialdehyde (MDA) increased in the
      ischemia-reperfusion areas (+101%), but FeAs-induced MDA did not vary in the area
      of permanent ischemia. Brain tissue undergoing ischemia-reperfusion was about 50%
      less sensitive to the antioxidant effect of ascorbic acid. The reduction of TPT
      showed 52% mitochondrial damage in the area of ischemia-reperfusion, whereas
      mitochondrial activity in the area of permanent ischemia was 177 times lower as
      compared to controls. d-alpha-tocopherol caused a 40% inhibition of MDA
      production and 16.5% and 21.5% decrease in mitochondrial activity in the areas of
      ischemia-reperfusion and permanent ischemia, respectively.

PMID- 8293316
TI  - Effect of tyrosine on cognitive function and blood pressure under stress.
AB  - The effects of tyrosine on mood, performance, heart rate and blood pressure of 16
      healthy young subjects were assessed. Subjects were tested on two separate days,
      one test session after ingestion of 100 mg/kg tyrosine and the other test session
      after placebo, in random order. While performing a number of stress sensitive
      tasks, subjects were exposed to a stressor consisting of 90 dB noise. Tyrosine
      was found to improve the performance on two cognitive tasks, which were performed
      1 h after administration of the medication and which could be characterized as
      highly sensitive to stress. In addition, tyrosine decreased diastolic blood
      pressure 15 min after ingestion, while 1 h after ingestion diastolic blood
      pressure was the same with tyrosine and placebo. No effects on mood, systolic
      blood pressure and heart rate were found.

PMID- 8293317
TI  - Distribution of androgen receptor-like immunoreactivity in the brains of intact
      and castrated male hamsters.
AB  - The distribution of androgen receptor-like (AR) immunoreactivity was mapped in
      brains of (a) intact, sham-castrated and (b) castrated male hamsters. The pattern
      of AR-immunoreactive (AR-ir) staining was, in general, similar to that reported
      for gonadal steroid autoradiography of the male hamster brain. Moreover, with one
      exception, AR-like staining was similar in intact and castrated males, and
      occurred in the medial preoptic area, bed nucleus of stria terminalis, amygdala,
      hippocampus, thalamus, and several hypothalamic nuclei including the
      periventricular, supraoptic, and ventromedial nuclei, and median eminence.
      However, while AR-ir labeling was virtually absent in the lateral septum of
      intact males, it was clearly present in the lateral septum of castrated males.
      The view that androgen receptors in brain generally decline after castration
      received no support from this study.

PMID- 8293318
TI  - Manganese (Mn) transport across the rat blood-brain barrier: saturable and
      transferrin-dependent transport mechanisms.
AB  - Using a single capillary pass technique, the transport of manganese (Mn) across
      the rat blood-brain barrier (BBB) was characterized. Initial rate measurements
      (15 s) of Mn2+ [0-1000 microM] accumulation in rat brains clearly indicated
      saturation kinetics by both 1/v vs. 1/s plots, and plots of v vs. [s]. Common
      carotid injection of freshly mixed Mn2+ with transferrin at a 1:10 molar ratio
      did not result in a significant change in the initial rate of Mn brain levels
      compared with injection of Mn2+ alone. However, when Mn2+ was incubated at 25
      degrees C in the presence of transferrin at a 1:10 ratio for up to 5 days prior
      to common carotid injection, the initial rate of Mn uptake by brain was
      incubation-time-dependent, increasing linearly with prolonged incubations. These
      findings suggest that the saturable component of divalent Mn transport into brain
      represents but one of the transport mechanisms for Mn across the BBB. A second
      transport system for Mn may occur by a transferrin-conjugated Mn transport
      system.

PMID- 8293319
TI  - Dynamic relationships between sleep spindles and delta waves during a NREM
      period.
AB  - All-night sleep EEGs from 7 normal young male adults were analyzed by a waveform
      recognition method using FFT-IFFT band pass filters. The total durations of sleep
      spindles and sleep delta waves in each 20-s epoch were measured and plotted on an
      X-Y graph with lines connecting the points in time sequence (dynamic two
      component plot). The relationship between these two measures within a single NREM
      period showed three dynamic phases and one stationary period. In the first phase,
      spindles increased while delta remained at low level or increased slightly. In
      the second phase delta increased greatly while spindles decreased. In the third
      phase, delta decreased while spindles remained at a low level. There was a
      stationary period between the second and third phases, when delta maintained a
      higher level and spindles maintained a lower level. These dynamic descriptions
      reflect the underlying physiological mechanisms more directly than static sleep
      stages. They should also permit finer analyses of sleep in psychiatric and
      neurological disorders.

PMID- 8293320
TI  - Algorithm and computer program Pro__Anal for analysis of relationship between
      structure and activity in a family of proteins or peptides.
AB  - In this paper we introduce a computer algorithm and program Pro__Anal for
      analysis of the structure-activity relationship in a family of evolutionarily
      related (and/or artificially mutated) proteins/peptides. The program uses aligned
      amino acid sequences with data of their activity (pK, Km, ED50 or any other) and
      searches for correlations between data on activity and various physico-chemical
      characteristics of different regions in primary structures. In automatic mode,
      the program generates and verifies hypotheses on the disposition of a sequential
      modulating region in a protein, and key characteristics of the region. In manual
      mode, users can generate and analyze their own hypotheses. The program is
      implemented on IBM PC or compatible computers. It is designed to be easily
      handled by the occasional computer user and yet it is powerful enough for
      experienced professionals. Pro__Anal operation is demonstrated on the example of
      finding modulating centers in a family of disintegrins-proteins from snake venoms
      which inhibit fibrinogen interaction with platelet receptors. In another example
      it is shown that the immunogenicity of peptides is connected with their positive
      charge.

PMID- 8293321
TI  - A weight array method for splicing signal analysis.
AB  - A new method of sequence analysis, using a weight array method (WAM), which
      generalizes the traditional Staden weight matrix method (WMM), is proposed. With
      the help of a statistical mechanical model, the discriminant function is
      identified with the energy function describing macromolecular interactions. The
      method is applied to the study of 5'-splice signals in Schizosaccharomyces pombe
      pre-mRNA sequences. The results show that there may exist weak pairwise
      correlations within the signals and that our method can help to better
      discriminate these signals. Experiments are proposed to test the predictions of
      the theory.

PMID- 8293322
TI  - PFGE MAPPER: a tool to aid in the analysis of pulse field gel electrophoresis
      maps.
AB  - Pulse field gel electrophoresis mapping is an important technique for
      characterizing large segments of DNA and constructing long-range restriction
      maps. We have developed a tool, PFGE MAPPER, to aid in the construction of pulse
      field electrophoresis gel maps. This tool helps construct pulse field gel maps
      from single and double digest experiments visualized by hybridization with single
      copy probes. The program is written in Think C and runs on Macintosh computers.
      An intuitive interface allows the user to interactively modify fragment sizes or
      errors, select fragments for analysis and recalculate the maps. Maps can be
      printed or saved for later viewing. After constructing and saving several maps in
      a region, PFGE MAPPER can be used to refine and extend the overall map by merging
      individual maps. This tool should be useful for constructing long-range
      restriction maps of genomic DNA and yeast artificial chromosomes.

PMID- 8293323
TI  - Development of predictive models of laboratory animal growth using artificial
      neural networks.
AB  - Traditional regression analysis of body weight growth curves encounters problems
      when the data are extremely variable. While transformations are often employed to
      meet the criteria of the analysis, some transformations are inadequate for
      normalizing the data. Regression analysis also requires presuppositions regarding
      the model to be fit and the techniques to be used in the analysis. An alternative
      approach using artificial neural networks is presented which may be suitable for
      developing predictive models of growth. Neural networks are simulators of the
      processes that occur in the biological brain during the learning process. They
      are trained on the data, developing the necessary algorithms within their
      internal architecture, and produce a predictive model based on the learned facts.
      A dataset of Sprague-Dawley rat (Rattus norvegicus) weights is analyzed by both
      traditional regression analysis and neural network training. Predictions of body
      weight are made from both models. While both methods produce models that
      adequately predict the body weights, the neural network model is superior in that
      it combines accuracy and precision, being less influenced by longitudinal
      variability in the data. Thus, the neural network provides another tool for
      researchers to analyze growth curve data.

PMID- 8293324
TI  - Connection topology of proteins.
AB  - One-dimensional amino acid sequences and three-dimensional folded polypeptide
      chains were modelled as non-directed graphs in which nodes corresponded to amino
      acids and arcs represented connections between them. In the case of folded
      chains, non-backbone connections were assigned to amino acid pairs if their
      distance was lower than a threshold. Two topological indices, the connectedness
      number and the effective chain length were devised to compare folding topologies.
      Loops created by non-backbone connections in the structure graphs were studied by
      simple graphical representations, revealing the hierarchy in native protein
      structures.

PMID- 8293325
TI  - SCANGRAPH: a program for digitization of graphs using an image scanner.
AB  - The program SCANGRAPH has been developed for vectorizing any drawing or graph in
      the form of a single continuous line. With the use of the software, the raster
      image of a graph in the TIFF format as generated from an optical scanner or
      digitizing video system can be converted to the corresponding digitized graph
      with x and y coordinates given. The digitized data can be output in the ASCII
      format for importing to other software packages. Options for peak identification,
      data smoothing and compression, and graph comparison are also provided for data
      manipulation.

PMID- 8293326
TI  - Estimation of the intrinsic rate of natural increase and its error by both
      algebraic and resampling approaches.
AB  - The intrinsic rate of natural increase or Malthusian parameter plays a key role
      fields as diverse as ecology, genetics, demography and evolution. It
      characterizes the growth of a population in a determinate environment. Since its
      rigorous statistical estimation requires of intensive calculation, the use of a
      computer becomes essential. The two main approaches to the calculation of the
      Malthusian parameter, its error and confidence intervals have been implemented in
      a program and have been compared by means of an example.

PMID- 8293327
TI  - FASTPAT: a fast and efficient algorithm for string searching in DNA sequences.
AB  - A new string searching algorithm is presented aimed at searching for the
      occurrence of character patterns in longer character texts. The algorithm,
      specifically designed for nucleic acid sequence data, is essentially derived from
      the Boyer-Moore method (Comm. ACM, 20, 762-772, 1977). Both pattern and text data
      are compressed so that the natural 4-letter alphabet of nucleic acid sequences is
      considerably enlarged. The string search starts from the last character of the
      pattern and proceeds in large jumps through the text to be searched. The data
      compression and searching algorithm allows one to avoid searching for patterns
      not present in the text as well as to inspect, for each pattern, all text
      characters until the exact match with the text is found. These considerations are
      supported by empirical evidence and comparisons with other methods.

PMID- 8293328
TI  - Notes on the implementation of the mass-radius method of fractal dimension
      estimation.
AB  - The graphical implementation in computers and image analysers of the mass-radius
      method of fractal dimension estimation has two sources of error. The first is
      associated with underestimation of area of the 'circle scan' in a square matrix;
      the second arises from the overestimation of areas at small radii. Methods of
      coping with these problems are described.

PMID- 8293329
TI  - GEPASI: a software package for modelling the dynamics, steady states and control
      of biochemical and other systems.
AB  - GEPASI is a software system for modelling chemical and biochemical reaction
      networks on computers running Microsoft Windows. For any system of up to 45
      metabolites and 45 reactions, each with any user-defined or one of 35 predefined
      rate equations, one can produce trajectories of the metabolite concentrations and
      obtain a steady state (if it does exist). When steady-state solutions are
      produced, elasticity and control coefficients, as defined in metabolic control
      analysis, are calculated. GEPASI also allows the automatic generation of a
      sequence of simulations with different combinations of parameter values,
      effectively scanning a hyper-solid in parameter space. Together with the ability
      to produce user-defined columnar data files, these features allow for both very
      quick and systematic study of biochemical pathway models. The source code (in C)
      is available on request from the author, and while the user interface is
      dependent on having MS-Windows as the operating system, the numerical part is
      portable to other operating systems. GEPASI is suitable both for research and
      educational purposes. Although GEPASI was written with biochemical pathways in
      mind, it can equally be used to stimulate other dynamical systems.

PMID- 8293330
TI  - Estimation of steady-state flux rates in metabolic systems by computer
      simulations of radioactive tracer experiments.
AB  - The dynamics of radioactive tracers in metabolic systems can be mathematically
      modelled by coupled systems of differential equations for both the concentrations
      and the specific radioactivities of the metabolites involved. Computer
      simulations, i.e. direct fitting of numerical solutions of these equations to
      observed time-courses of metabolites and specific radioactivities, enables one to
      estimate unknown kinetic parameters of the system. The theoretical fundamentals
      of this approach and the main steps towards the quantitative assessment of flux
      rates in stationary metabolic systems are outlined. An application of the method
      to the purine nucleotide metabolism of Ehrlich ascites tumor cells is given based
      on a simplified model of this pathway. The obtained steady-state flux rates
      indicate a marked increase in the metabolism of the adenine nucleotides during
      the proliferating phase in comparison to the resting phase of tumor growth.

PMID- 8293331
TI  - A general UNIX interface for biocomputing and network information retrieval
      software.
AB  - We describe a UNIX program, HYBROW, which can integrate without modification a
      wide range of UNIX biocomputing and network information retrieval software.
      HYBROW works in conjunction with a separate set of ASCII files containing
      embedded hypertext-like links. The program operates like a hypertext browser
      featuring five basic links: file link, execute-only link, execute-display link,
      directory-browse link and field-filling link. Useful features of the interface
      may be developed using combinations of these links with simple shell scripts and
      examples of these are briefly described. The system manager who supports
      biocomputing users should find the program easy to maintain, and useful in
      assisting new and infrequent users; it is also simple to incorporate new
      programs. Moreover, the individual user can customize the interface, create
      dynamic menus, hypertext a document, invoke shell scripts and new programs simply
      with a basic understanding of the UNIX operating system and any text editor. This
      program was written in C language and uses the UNIX curses and termcap libraries.
      It is freely available as a tar compressed file (by anonymous FTP from
      nuscc.nus.sg).

PMID- 8293332
TI  - Block searches on VAX and Alpha computer systems.
AB  - A new program, BlockSearch, is described that allows biologists to search protein
      sequences against the BLOCKS database of aligned protein blocks by converting
      these blocks to site-specific scoring matrices. It thus complements existing
      tools for standard similarity searches and pattern searches which aid in
      elucidating the function of newly determined protein-coding sequences. The speed
      of the program and the existence of a command-line interface render BlockSearch
      particularly interesting for the batch analysis of many new sequences, such as
      collections of expressed sequence tags. Although written primarily for Digital's
      Alpha and VAX systems, the code is easily portable to other platforms.

PMID- 8293333
TI  - Driving multiple pulsed field electrophoresis devices from one personal computer.
AB  - A PC has been programmed to control more than one pulsed field electrophoresis
      device (e.g. clamped homogeneous electric field, CHEF; field inversion gel
      electrophoresis, FIGE). Each device is assumed to have a field controller
      requiring signals to (i) switch the field on/off, (ii) re-orient the field and
      (iii) invert the field. An interface between the computer parallel port and up to
      four devices is suggested and this was built from standard TTL logic and optical
      couplers. Software has been written to drive all four devices in parallel. Each
      pulsed field device may have a totally independent pulse regime, may be stopped
      or started at random and may be monitored at any time during an experiment.
      Setting up and running each device is almost entirely by mouse control and
      frequently used pulse regimes may be saved and rapidly retrieved from hard or
      floppy disk. The software can be configured for any combination of CHEF and FIGE
      devices.

PMID- 8293334
TI  - Computer simulation of selection in a hypothetical crop species.
AB  - A computer simulation model demonstrating the effect of directional selection
      upon a simplified quantitative genetic character, is presented. Complementary
      homozygous parents were crossed to generate a fully heterozygous F1 population.
      Phenotypic truncation selection was effected upon the F2 and subsequent
      generations, and genotypic and phenotypic response to selection, as well as the
      change in population heterozygosity, was monitored to generation F9. The model
      simulates selection for alternative breeding regimes, modes of allelic
      interaction, selection pressure, population size and levels of environmental
      variation. Three alternative methods for the simulation of the environmental
      component of phenotypic variance are incorporated, and mechanisms and relative
      merits of the rival methods are discussed. Data generated by the model conformed
      closely to theoretical expectation, lending support to the use of the model as a
      platform for development of more comprehensive simulation models. Potential
      improvements to the model are discussed.

PMID- 8293335
TI  - PERFILS: a program for the quantitative treatment of footprinting data.
AB  - PERFILS, a computer program written in Borland TurboPascal, performs quantitative
      analysis of footprinting experiments using any IBM PC or compatible
      microcomputer. The program uses the height of the bands obtained from
      densitometric scanning of footprinting autoradiographs to calculate a
      differential cleavage plot. Such a plot displays, on a logarithmic scale, the
      difference of susceptibility of a DNA fragment to DNase I, or any other cleaving
      agent, in the presence of any ligand versus the sequence. PERFILS calculates the
      fractional cleavage values for control and ligand, giving a table of values for
      each internucleotidic bond and rendering the differential cleavage plot in only a
      few seconds.

PMID- 8293336
TI  - [Diagnosis and treatment of children with congenital heart diseases in China].

PMID- 8293337
TI  - [Advances in gene therapy].

PMID- 8293338
TI  - [Morphology of right ventricle and hemodynamics in pulmonary atresia with intact
      ventricular septum].
AB  - Cardiac catheterization and angiography were performed in 31 patients with PA/IVS
      to evaluate the morphology of RV and hemodynamics. The age of patients ranged
      from 1 day to 39 month (mean 4.7 month). The patients were divided into three
      groups: mild (19.4%), moderate (64.5%) and severe (16.1%) RV hypoplasia,
      according to the degree of tricuspid valve and right ventricular hypoplasia.
      Seven of the 31 patients (22.6%) had right ventricular myocardial sinusoid
      coronary artery fistula. The right and left ventricular pressures in 26 patients
      were measured simultaneously. The right ventricular pressures were supra-systemic
      in 18 patients (69.2%), systemic in 6 (23.1%), less than systemic pressures in 2
      (7.7%); the others were PA/IVS with ASD(6 patients), PFO (25), PDA (25).
      Palliative and definitive operations were performed on 22 patients. The results
      show that determining the morphology of RV and the hemodynamics before operation
      is helpful in selecting appropriate operation for lowering the operative
      mortality.

PMID- 8293339
TI  - [Diagnosis and treatment of infantile endocardial fibroelastosis].
AB  - The diagnosis, treatment and etiology of primary infantile endocardial
      fibroelastosis were studied in 33 patients from 1989 to 1992. Two dimensional
      echocardiography with Doppler examination showed that the thickness of the
      endocardium obviously increased and systolic and diastolic functions of the left
      ventricles were abnormal. Endomyocardial biopsy proved that the endocardium and
      myocardium under went pathological changes. The virus probe examination of biopsy
      tissue showed negative results and the effectiveness of immunosuppressive therapy
      (total effective rate 96%) indicated that this disease is probably of autoimmune
      etiology. The facts led us to nominate this disease as infantile endomyocardial
      disease. Besides, the classification, diagnostic criteria, principles of
      treatment and prognosis of this disease were discussed.

PMID- 8293340
TI  - [Changes of endothelin in rats with normobaric hypoxia-induced pulmonary
      hypertension].
AB  - A model of pulmonary hypertension was established in rats by method of normobaric
      hypoxia to study the possible pathophysiological role of endothelin (ET) and
      other vasoactive substances in normobaric hypoxia-induced pulmonary hypertension.
      The ET levels of the lung and plasma, atrial natriuretic peptide (ANP) and
      angiotensin II level of plasma were measured by specific radioimmunoassay. The
      pulmonary arterial pressure (PAP) in hypoxic rats was significantly higher than
      that of the control. The ET level of plasma in hypoxic rats was significantly
      increased. The ET level of plasma was positively correlated with PAP in hypoxic
      rats. The ANP level of plasma was also increased, and the ET level of plasma was
      positively correlated with the ANP level of plasma in hypoxic rats.

PMID- 8293341
TI  - [Portal angiography and color Doppler for portal hemodynamics research].
AB  - The portal developing rates of 0%, 10%, 35% and 55% in portal hypertension were
      detected by prostaglandin E1(PGE1) indirect portal digital subtraction
      angiography (DSA). The rates of left gastric vein (LGV), short gastric vein
      (SGV), umbilical vein (UV) and spontaneous splenorenal Vein shunt collateral were
      80%, 45%, 25% and 5% respectively and the confluent point of LGV was shown
      directly. Time--density curve depict showed that the hepatofugal blood flow rates
      of the main portal vein and splenic vein were 10% and 15% respectively. Color
      Doppler showed not only the imageology of the portal system, but the blood flow.
      The developing rates of LGV, SGV, UV and spontaneous splenorenal vein shunt
      collateral were 80%, 5%, 10% and 85% respectively. Following the improvement of
      portal developing grades, the main portal vein flow, splenic vein flow, and
      superior mesenteric vein flow were decreased. The results indicates the more
      poorly hepatopetal flow irrigation, the more intensive condition in high
      hemodynamics of the portal system.

PMID- 8293342
TI  - [Hip prosthetic stem biological fixation by compound bone-cement].
AB  - Thirty rabbits were subjected to hemiarthroplasty for the right hip. The
      prosthetic stems were fixed by DBM + bone-cement in group I, BMG + bone-cement in
      group II, bone-cement only in group III, and uncemented inserting stem in group
      IV. They were periodically examined roentgenologically, histologically and
      biomechanically. Group I and II attained early mechanical fixation and new bone
      grew into the compound bone-cement (CBC), which was fused together with the host
      bed. Their shearing strength of the contact surface of CBC was increased with
      time. The differences between group I, II and group III, IV were obvious (P <
      0.01). In later stage, group III showed bone absorption and destruction, and
      pseudo-membraneous tissue between the bone and cement. Group IV failed in
      fixation and had loosening and subsidence of the stems even in the early stage.
      The histology and biomechanics of compound bone-cement were also discussed.

PMID- 8293343
TI  - [Cordyceps sinensis in protection of the kidney from cyclosporine A
      nephrotoxicity].
AB  - To explore the protective effect of cordyceps sinensis (CS) on cyclosporine A
      nephro-toxicity (CsA-Nx) and the possible mechanism, we studied the kidney
      changes induced by CsA in rats by light microscopy (LM), electronic microscopy
      (EM) and morphometrical analysis. At the 15th day after receiving CsA, prominent
      vacuolation and necrosis were noted microscopically in proximal tubular cells and
      mitochondria swelling electronmicroscopically. Morphometrical study showed that
      the epithelial areas of both proximal and distal tubules in the CS group were
      larger than those of the control group. There were obvious vacuolation (90%) and
      necrosis in proximal tubular cells at different stages of chronic CsA-Nx.
      Interstitial edema with mild fibrosis was observed. Mitochondria abnormality was
      seen electronmicroscopically. Morphometrical analysis showed that the epithelial
      cell areas of tubules and glomeruli were smaller in the CsA group than those in
      the CS group. Both acute and chronic experiments showed that CS could protect the
      kidney from CsA-Nx and ameliorate the glomerular and interstitial injuries.

PMID- 8293344
TI  - [Grafting of autogenous jugular vein and glutaraldehyde-stabilized human
      umbilical vein in dogs].
AB  - The glutaraldehyde-stabilized human umbilical cord vein (HUV) was implanted to
      the intrarenal aorta in dogs, by using autogenous jugular vein (AJV) as control.
      The healing mechanism was shown by angiography, radioisotope scanning Doppler
      ultrasound, LM, SEM and TEM. The patency rate in 6 months was 95.2% in AJV and
      87.5% in HUV. No significant difference was noted between the two veins (P >
      0.05). Pathohistological study of AJV and HUV after implantation showed that
      there were three stages: acute injury, acute inflammatory reaction and
      hyperplastic repairing of tissues. The new endothelial cells of AJV grew earlier
      and faster than those of HUV. But, both veins were endothelialized 6 months after
      operation. The subendothelium of new intima consisted of fibroblasts and collagen
      fibres less myointimal cells derived from smooth muscle cells in the media. The
      media and the adventilized were replaced by fibrous connective tissue. HUV
      stabilized with 0.5% glutaraldehyde for grafting caused no immunologic rejection,
      and had the structure of the venous wall and antithrombotic function, keeping the
      grafts patent.

PMID- 8293345
TI  - [Anoxia-reperfusion injury to endothelial cells: mechanism and protection].
AB  - Endothelial cells in the aortic walls of inbred SD rats were cultured in MEM
      culture medium containing 10% calf serum, and an anoxia-reperfusion injury model
      was established. The effect of anoxia-reperfusion injury on cultured endothelial
      cells was studied by measurements of membrane fluidity, intracellular Ca content,
      the release rate of 51Cr and the uptake rate of trypan-blue. The effect of
      fructose 1-6 diphosphate (FDP) and captopril (Cap) on cultured endothelial cells
      was also investigated. The findings indicated that the two drugs might protect
      cultured endothelial cells from anoxia-reperfusion injury. The mechanism of
      anoxia-reperfusion injury and the protective effect of the two drugs on cultured
      endothelial cells were briefly discussed.

PMID- 8293346
TI  - [The effect of high energy shock waves on growth and metastasis of implanted
      tumors of nude mice in vivo].
AB  - We observed the effect of high energy shock waves (HESW) on tumor growth,
      histological and ultrastructural variations, and metastasis to lymph nodes and
      viscera in nude mice with implanted tumors. HESW was cytotoxic to tumors in vivo,
      and acted on levels of cell membrane, cytoplasmic organelles, and nuclear
      chromatins. At definite working voltage, this effect was positively proportional
      to the impulse number. Histological examination showed no metastatic focci to
      lymph nodes and viscera of nude mice with implanted tumors. The possible
      mechanism of HESW in vivo may be direct mechanical damage and indirect inhibition
      of tumor growth due to damage to the blood supply. Other hypotheses were also
      discussed.

PMID- 8293347
TI  - [Antineoplastic action of adenosine triphosphate].

PMID- 8293348
TI  - The antiquity of osteoporosis: more questions than answers.

PMID- 8293349
TI  - Osteoporosis, metabolic aberrations, and increased risk for vertebral fractures
      after partial gastrectomy.
AB  - A case-control study compared 129 men with earlier partial gastrectomy (operation
      during the period 1952-1961) with 216 men from a community-based population
      study. All were born 1910-1915 and the mean age was 72 years. Men with a previous
      partial gastrectomy had vertebral fractures in 19% compared with 4% (P < 0.01) in
      the control population. Bone mineral density (BMD) in the right calcaneus
      measured with dual energy photon absorptiometry was 20% lower in men with a
      Billroth II operation (P < 0.001) and 8% lower with a Billroth I operation (ns).
      In comparison with the controls, the men subjected to partial gastrectomy had
      higher serum concentrations of osteocalcin and alkaline phosphatase activity, a
      lower serum concentration of 25-hydroxyvitamin D (25OHD) and a lower body mass
      index (BMI). There were no difference in serum concentrations of free calcium,
      intact parathyroid hormone (PTH), or free thyroxine. The smoking prevalence was
      significantly higher in men with partial gastrectomy than in controls. Smokers
      had significantly lower serum concentrations of intact PTH and 25OHD than
      nonsmokers and also lower BMD and BMI. The relationships between intact PTH on
      one hand, and ionized calcium (inverse relationship) and osteocalcin (direct
      relationship) on the other were preserved in smokers, however. Gastroscopy was
      performed in 78 men with multiple biopsies in the gastric remnant and also in the
      small intestine. All but two subjects had chronic gastritis. Examination of
      sternal bone marrow smears showed that 40% of the Billroth-operated men lacked
      bone marrow reticular iron.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293350
TI  - The relationship between serum intact parathyroid hormone and calcium in
      idiopathic hypoparathyroidism.
AB  - We studied the relationship between serum calcium (Ca) and parathyroid hormone
      (PTH) in patients with idiopathic hypoparathyroidism (IHP) to investigate the
      diversity of the degree of parathyroid insufficiency and a regulation of PTH
      secretion by Ca in IHP. Serum intact PTH concentrations ranged from < 1.0 to 10.3
      pg/ml in 20 patients with IHP and were above the detection limit in 18 (90%)
      patients. Serum total Ca levels in IHP were positively correlated with serum
      intact PTH (r = 0.824, P < 0.001), in contrast with a negative correlation
      between serum intact PTH and Ca in 91 normal subjects (r = -0.378, P < 0.001) and
      abnormally high serum intact PTH values against hypocalcemia in five patients
      with pseudohypoparathyroidism. In three patients with IHP, serum intact PTH
      decreased in response to treatment with active vitamin D3 which increased serum
      Ca and 1,25(OH)2D. An inverse sigmoidal relationship between serum ionized Ca and
      intact PTH was demonstrated in a patient with IHP before treatment [IHP(-)] and
      three patients with IHP treated with active vitamin D3[IHP(+)]. Peak serum intact
      PTH values were reduced in IHP(-) and IHP(+). Baseline serum intact PTH was 77.0%
      of the maximal level in IHP(-), 51.7-72.1% in IHP(+), and 31.1-42.3% in five
      normal subjects. The degree of parathyroid dysfunction in IHP differs from one
      patient to another and serum Ca levels are thought to be determined by
      circulating PTH levels. Although PTH secretory reserve is diminished, PTH
      secretion is negatively regulated by Ca and is stimulated at baseline in patients
      with IHP before and during the treatment with active vitamin D3.

PMID- 8293351
TI  - Evidence of absorptive hypercalciuria in tuberculosis patients.
AB  - In patients with granulomatous diseases, disturbances in calcium metabolism have
      been described. The aim of the study was to evaluate alterations in calcium
      metabolism in patients with tuberculosis. Forty patients with tuberculosis (TB)
      were studied in a baseline state (calcium intake 1000 mg/day). Fourteen of these
      patients were also studied after restrictive calcium diet (400 mg/calcium/day)
      and after a load of oral calcium of 1000 mg. In all the studies, calcium and
      phosphorus were measured in serum and urine, and parathyroid hormone (PTH) in
      plasma. In addition, serum 25OHD and 1,25(OH)2D (calcitriol) levels were measured
      in the baseline state and after the restrictive diet. In the baseline state,
      25OHD levels were lower and urinary calcium higher in TB patients than in the
      control group. No patients had hypercalcemia, but hypercalciuria was present in
      10 patients (25%). The patients with tuberculosis were divided according to the
      presence or absence of hypercalciuria. In both groups, the 25OHD levels were
      lower than in controls. Hypercalciuric patients had lower plasma parathyroid
      hormone levels and higher serum calcitriol levels than the control group and the
      TB patients without hypercalciuria. Urinary calcium excretion after a calcium
      load was higher in TB patients with hypercalciuria than in controls. A positive
      correlation was found between the calcitriol levels and postcalcium load urinary
      calcium excretion in patients with calcium hyperabsorption. These data indicate
      that absorptive hypercalciuria is frequently observed in patients with TB and is
      possible due to inappropriately high serum calcitriol levels.

PMID- 8293352
TI  - Total body, spine, and femur dual X-ray absorptiometry in spinal osteoporosis.
AB  - The aim of this study was to evaluate the ability of dual x-ray absorptiometry
      (DXA) to discriminate between normal and osteoporotic patients. A total of 152
      postmenopausal women entered the study: 73 (aged 61.2 +/- 8 years) had
      established postmenopausal osteoporosis with one or more vertebral crushes on
      lateral X-ray of spine, and 79 (aged 59.3 +/- 7.8 years) had no vertebral
      fractures. Measurements of bone mineral content (BMC) in grams, bone mineral
      density (BMD) in g/cm2 and body composition (lean and fat mass in grams) of total
      body, lumbar spine (L2-L4), and femur (neck, trochanter, Ward's triangle) were
      carried out with a LUNAR DPX densitometer. In all sites, BMD values of
      osteoporotic patients were significantly lower than those of the control
      subjects. The higher Z-score was found for total body density (-2.14) followed by
      L2-L4 (-2.0), femoral neck (-1.93), Ward's triangle (-1.69), and trochanter (
      1.4). Only the trochanter Z-score was significantly different compared with the
      other sites. A fracture threshold was determined for each site from osteoporotic
      patients and normal controls: with a sensitivity set at 90%, the best specificity
      was obtained at the lumbar spine and total body sites (89% and 84%,
      respectively). BMD values were highly related to lean and fat body mass, but bone
      loss with age was unrelated to soft tissue change. In conclusion, BMD
      measurements at different skeletal sites enable detection of spinal osteoporosis
      although sensitivity for femoral areas was less with respect to total body and L2
      L4 BMD values.

PMID- 8293353
TI  - Parathyroid hormone (1-34) and (1-84) stimulate cortical bone formation both from
      periosteum and endosteum.
AB  - The anabolic effect of intermittent treatment with parathyroid hormone (PTH) on
      cortical bone was investigated. Groups of rats were injected with human PTH (1
      34) or PTH (1-84), 1.1, 3.3, 10, and 30 nmol/kg/day for 30 days. A dose-related
      increase in bone formation rate at the femoral middiaphysis was found at both the
      periosteum and the endosteum and also an increase in bone mass, with no change in
      the bone lengths or body weight gain of the rats. The highest mineral apposition
      rate, as analyzed by tetracycline labeling, was found at the periosteal postero
      medial aspect and at the endosteal anterior aspect. This pattern of bone modeling
      was also found in the PTH-treated animals, although more and more areas were
      included in bone mineral apposition. The PTH treatments did not change the
      porosity of the cortical bone nor the concentration and biochemical stability of
      the collagen. The highest doses of PTH resulted in a slight reduction in the ash
      concentration of cortical bone. No differences were found between the effects of
      PTH (1-34) and PTH (1-84) on bone formation rate, bone mass, porosity, and
      biochemical parameters. Consequently, intermittent treatment with PTH increased
      the formation of cortical bone dose dependently, at both the periosteum and the
      endosteum and increased the bone mass of these growing rats, with no change in
      the body weight gain or femoral growth rate compared with the control animals.
      The responses of the cortical bone modeling were increased by the PTH treatments
      without changing its direction or pattern.

PMID- 8293355
TI  - Intraarterial protamine sulfate reduces the magnitude of streaming potentials in
      living canine tibia.
AB  - Using previously described techniques, transcortical streaming potentials were
      measured at two middiaphyseal sites on one tibia of each of nine anesthetized
      canines during sinusoidal bending (approximately 0 to -200 mu epsilon periosteal
      surface strain) at 2 Hz. Measurements were made for 60 minutes prior to and up to
      180 minutes following bolus injection of protamine sulfate (42-126 mg/kg)
      dissolved in Hanks Balanced Salt Solution, directly into the femoral artery
      without interrupting circulation. Shortly after injection, the protamine sulfate
      caused a clear reduction in the magnitude of streaming potentials. Subsequent
      injections of additional protamine sulfate resulted in further reductions, and in
      several instances, voltage sign reversals. This study represents the first
      observation that circulating proteins may alter electromechanical transduction in
      living bone, and suggests the possibility that specific agents, which are known
      to affect bone remodeling, may do so, in part, by altering these endogenous
      electrical potentials.

PMID- 8293354
TI  - The effect of gallium nitrate on healing of vitamin D- and phosphate-deficient
      rickets in the immature rat.
AB  - The effect of gallium on rapid in vivo mineralization was studied in a rachitic
      rat model in which rickets were induced in immature rats then reversed ("healed")
      with repletion of vitamin D and phosphate. Gallium was administered to selected
      groups of animals before and during the healing phase. In nonrachitic animals and
      rachitic animals before healing, the mineral content of diaphyseal and
      metaphyseal bone was increased, and the crystal size was decreased in those
      animals that received gallium compared with those that did not. Mineralization of
      the undermineralized osteoid appeared histologically normal by 72 hours in all
      animals. However, animals that received gallium both before and during the
      healing phase had less well-mineralized bones at 18 hours, and by 72 hours, they
      had lesser increases in osteocalcin and mineral content, which was associated
      with smaller crystal sizes, than did any animal that did not receive gallium at
      any time. Prior to the healing phase, the ratio of gallium to hydroxyproline in
      the metaphyses of rachitic animals was similar to that in nonrachitic animals.
      Likewise, this ratio did not change in the animals receiving gallium both before
      and during the healing phase. The ratio of gallium to calcium was higher in
      rachitic animals compared with controls, and this ratio lowered significantly by
      the end of the healing phase. Results may be explained in part by direct effect
      of gallium on the physical process of mineral formation during the rapid healing
      phase as well as by effects of gallium on osteoblasts and osteoclasts during the
      induction of rickets.

PMID- 8293356
TI  - Spectrum decomposition through maximum likelihood common factor analysis of the
      EPR spectra of Na+ containing carbonated apatites dried at 400 degrees C.
AB  - X-irradiated carbonated apatites precipitated from aqueous solutions and dried at
      400 degrees C until constant weight are investigated with electron paramagnetic
      resonance (EPR). The carbonate content of the samples studied ranges from 8.12 to
      21.0 wt%. The observed multicomponent EPR spectra are analyzed with maximum
      likelihood common factor analysis (MLCFA), a multivariate statistical technique.
      Once the correct number of constituents are determined and the factor spectra
      estimated by MLCFA, a minimization procedure is performed in order to transform
      the abstract factor spectra linearly into an equal number of real EPR powder
      spectra. The spin hamiltonian parameters of the component spectra thus obtained
      are used to characterize and identify the different paramagnetic radicals. A
      comparison with values from the literature is made. A spectrum decomposition
      study of all the observed multicomponent EPR spectra in terms of the isolated
      constituents is successfully performed as a function of the carbonate content of
      the samples.

PMID- 8293357
TI  - Periosteal attachment fibers in the rat calvarium.
AB  - The anatomical relationships between the fiber tracts and bone lining cells
      within the rat calvarial periosteum have been studied by electron microscopy.
      Classical Sharpey's fibers were not observed in this location. Rather, thin
      unmineralized fibers originating from the periosteum traversed the cambial layer
      and passed to the bone surface between individual osteoblasts or groups of
      osteoblasts. The organizational relationship suggests that the osteogenic
      calvarial cell populations are compartmentalized into domains that might be
      particularly sensitive and responsive to the biomechanical forces of masticatory
      muscles.

PMID- 8293358
TI  - Taking notes from the corporate world: how re-engineering is revolutionizing
      business.

PMID- 8293359
TI  - Ketorolac versus ibuprofen: a simple cost-efficacy comparison for dental use.

PMID- 8293360
TI  - Working time of synthetic elastomeric impression material.
AB  - This study will introduce a new method for measuring the working time of
      elastomeric impression materials, taking into account the perceived shortcomings
      of existing systems for evaluating these times. The working times of various
      commercially available polysulfide, addition reaction silicones and polyethers
      were determined at room temperature (20 degrees C), following storage in a
      refrigerator (6 degrees C), and at mouth temperature (35 degrees C). At room
      temperature, the polysulfides demonstrated the longest working times and the
      silicones the shortest. Both the polysulfides and the silicones had longer
      working times following storage at 6 degrees C for 24 hours. However, the
      polyethers were found to be unusable at this temperature. All the impression
      materials had shorter working times when placed into the testing apparatus, which
      had been heated to mouth temperature.

PMID- 8293361
TI  - Intracoronal bleaching: concerns and considerations.
AB  - The history of intracoronal bleaching and the development of the walking bleach
      technique are reviewed. External cervical resorption associated with intracoronal
      bleaching is a serious sequela that has been reported in the literature. One
      explanation given for this phenomenon is that it results from an inflammatory
      process initiated by the presence of bleaching agents in the attachment
      apparatus. The basis for this conclusion is discussed. A review of published case
      reports on external cervical resorption associated with intracoronal bleaching
      revealed that: 100 per cent of the affected teeth had no intermediate dental base
      placed, 84 per cent were treated with a thermocatalytic technique, 80 per cent
      were bleached after the root canal sealer was fully set and 72 per cent had a
      history of trauma before bleaching. Based on these observations, it should be
      possible to safely bleach teeth intracoronally provided specific concerns and
      considerations are taken into account. These are: 1) the use of heat should be
      avoided; 2) an intermediate dental base should be placed with due respect to the
      attachment level; and 3) a base should be selected with due respect to its
      effectiveness in sealing tooth structure.

PMID- 8293362
TI  - Stress situations in dental practice.
AB  - Several studies indicate that stress is inherently present in dental practice.
      The present study was conducted to help identify the factors underlying this
      stress and the relative contribution of each factor. A questionnaire presented
      participating dentists with 52 potentially-stressful situations related to dental
      practice. Respondents were asked to rate each situation on a five-point scale,
      using a range of responses that varied from "not stressful" to "exceedingly
      stressful," and "I don't know" to "not applicable." The present data are based on
      the ratings given by the 1,332 dentists practicing in Quebec who answered the
      questionnaire (52 per cent). Ten situations received a mean score of greater than
      3.0, and were therefore considered as above average stress-producing situations.
      The majority of these situations could be classified as being related either to
      dental procedures and office organization or to interpersonal relationships
      involving patients and/or office personnel. It was found that the older age
      groups showed significantly less stress for six of the 10 most stressful
      situations. This study has indicated the specific situations that most frequently
      lead to stress in dentists. The precise identification of these situations could
      lead to reduced stress through the elimination of its vague and insidious
      character. Furthermore, an understanding of the most common stress-causing
      situations allows the practitioner to take preventive measures to eliminate its
      damaging effects in the dental practice.

PMID- 8293363
TI  - Radiography in dentistry. 1935.

PMID- 8293364
TI  - A physician who came home.

PMID- 8293365
TI  - Shortage of MRI equipment.

PMID- 8293366
TI  - Waiting for surgery.

PMID- 8293367
TI  - Lessons from Britain.

PMID- 8293368
TI  - Lessons from Britain.

PMID- 8293369
TI  - Lessons from Britain.

PMID- 8293370
TI  - Medical condition while driving.

PMID- 8293371
TI  - Neurologic injury after vaccination: buttocks as injection site.

PMID- 8293372
TI  - Thiazide therapy for diabetes.

PMID- 8293373
TI  - Breast cancer surgery: who chooses and how?

PMID- 8293374
TI  - Fatal anaphylactic reactions to food in children. Allergy Section, Canadian
      Paediatric Society.

PMID- 8293375
TI  - Variation in breast cancer surgery in Ontario.
AB  - OBJECTIVES: To analyse the extent of variation by county and hospital in the use
      of breast-conserving surgery in the initial management of breast cancer and to
      assess some factors that might explain the observed variation. DESIGN: Population
      based retrospective cohort study. SETTING: Ontario. PATIENTS: All women with
      breast cancer newly diagnosed from Jan. 1, 1989, to Dec. 31, 1991. MAIN OUTCOME
      MEASURE: Proportion of women undergoing unilateral breast cancer surgery who had
      breast-conserving surgery in each hospital and county. RESULTS: Of the 14,570
      women with newly diagnosed breast cancer 12,815 (88.0%) underwent unilateral
      breast cancer surgery. The mean proportion of breast-conserving procedures by
      county was 52% and ranged from 11% to 84%. The proportion of breast-conserving
      procedures in individual hospitals with one or more cases of breast cancer per
      month ranged from 6% to 84%. The variations in the rates between hospitals was
      greater than that expected by chance alone (p < 0.0001). CONCLUSIONS: There was
      marked variation at the hospital and county level in the use of breast-conserving
      surgery in the initial management of breast cancer. This variation was strongly
      associated with the hospital where the surgery was performed.

PMID- 8293376
TI  - Utilization of sigmoidoscopy by family physicians in Canada.
AB  - OBJECTIVE: To determine the extent to which sigmoidoscopy is used as an
      investigative tool by family physicians in Canada. DESIGN: Retrospective study of
      data from provincial and territorial health agencies for the fiscal year 1989.
      SETTING: Canada. PARTICIPANTS: All family physicians. MAIN OUTCOME MEASURES:
      Number of physicians in each province and territory who performed sigmoidoscopy
      (flexible and rigid), type of physician (generalist or specialist), number of
      procedures performed, fee schedule and number of physicians billing medicare in
      each province and territory. RESULTS: During the study period 3849 (15.1%) of all
      family physicians performed rigid sigmoidoscopy; the proportion varied from 3.4%
      (in Quebec) to 40.0% (in the Northwest Territories). A total of 43,914 rigid
      sigmoidoscopies were performed by family physicians, representing 23% of all such
      procedures. Flexible sigmoidoscopy was performed by 381 (1.5%) of all family
      physicians; the proportion varied from 0.4% (in Quebec) to 6.8% (in Prince Edward
      Island). A total of 5361 flexible sigmoidoscopies were performed, representing
      6.0% of all such procedures. CONCLUSION: The proportion of Canadian family
      physicians who are using sigmoidoscopy, rigid or flexible, as a diagnostic tool
      is low.

PMID- 8293377
TI  - Paranoid psychosis induced by oxymetazoline nasal spray.

PMID- 8293378
TI  - Gene therapy: the future touches down.

PMID- 8293379
TI  - MDs have significant role in helping learning-disabled children.

PMID- 8293380
TI  - Vancouver psychiatrist's experiences lead to work with torture victims.

PMID- 8293381
TI  - Toronto psychiatrist a world leader in study, treatment of torture victims.

PMID- 8293382
TI  - "The greatest devotion to duty": Dr. Francis Scrimger and his Victoria Cross.

PMID- 8293383
TI  - Age--is it a risk factor in ovarian cancer?

PMID- 8293384
TI  - A phase II study of outpatient chemotherapy with cisplatin, 5-fluorouracil, and
      leucovorin in nasopharyngeal carcinoma.
AB  - BACKGROUND: Systemic disease progression occurs in the majority of patients with
      locally advanced nasopharyngeal carcinoma (NPC). Although a variety of
      chemotherapeutic drugs have had tumoricidal activity, the roles of chemotherapy
      and optimal regimens must be further defined. Based on high response rates of
      Cisplatin, 5-Fluororacil and Leucovorin (PFL) in patients with advanced squamous
      cell cancers of the head and neck, we tested a new outpatient PFL chemotherapy
      program in patients with advanced NPC. METHODS: Patients with NPC and 1)
      previously untreated, locally advanced disease; 2) local regional recurrence (LR)
      after radiotherapy; or 3) metastatic disease were eligible for study. Cisplatin
      20 mg/m2/d, 5-FU 800 mg/m2/d and Leucovorin 90 mg/m2/d were administered
      simultaneously by continuous 96-hour intravenous infusion every three weeks.
      Patients were evaluated for response, survival, and toxicity. RESULTS: Thirty
      five patients were studied. The response rates of PFL therapy were 100% (15%
      complete response [CR], 85% partial response [PR]) in 20 patients with locally
      advanced or locally recurrent disease, and 80% (13.3% CR, 67.7% PR) in 15
      patients with metastatic disease. The overall median survival was 20 months after
      therapy (range, 2-21). The median survival rate for previously untreated, locally
      advanced patients was not reached. The median survival rate for previously
      treated, local recurrence was 34 months and for metastatic patients was 14
      months. Mucositis and leukopenia were the dose-limiting toxicities (20-23%, grade
      III) and occurred more frequently in patients previously irradiated. No treatment
      related deaths occurred. CONCLUSIONS: Outpatient PFL chemotherapy is active,
      safe, and convenient for advanced stage nasopharyngeal carcinoma patients, and
      the overall toxicities are tolerable.

PMID- 8293385
TI  - Cholesterol content in tumor tissues is inversely associated with high-density
      lipoprotein cholesterol in serum in patients with gastrointestinal cancer.
AB  - BACKGROUND: The authors have previously demonstrated in different experimental
      models that sustained processes of cellular growth are characterized by
      alterations of cholesterol metabolism not only in the proliferating tissues but
      also in the plasma compartment. METHODS: To evaluate whether alterations of
      cholesterol metabolism similar to those observed in experimental models are also
      associated with human cancer, in the present study cholesterol distribution in
      tumor tissues and lipid composition in the plasma compartment were determined in
      patients with different types of gastrointestinal cancer. RESULTS: The results
      showed that tumor tissues contain increased amounts of cholesterol when compared
      with the corresponding normal tissues. Intracellular alterations of cholesterol
      were accompanied by specific changes of cholesterol in the plasma compartment:
      high-density lipoprotein (HDL) cholesterol was markedly reduced in the serum of
      patients with gastrointestinal cancer and the lipoprotein profiles showed a
      decrease in HDL3 fraction, the main HDL subfraction in human serum. The decrease
      of HDL cholesterol was negatively associated with the clinical stage of the
      disease. No changes in either total or low-density lipoprotein cholesterol levels
      were observed. CONCLUSIONS: A major function attributed to HDL is to maintain
      normal cell cholesterol homeostasis by removing excess of cholesterol from
      intracellular pools. Because the use and storage of cholesterol are increased
      within the tumor tissues during growth, it is possible to hypothesize that low
      HDL levels observed in patients with gastrointestinal cancer are associated with
      the increased cholesterol metabolism in proliferating tissues.

PMID- 8293386
TI  - Expression of nm23 H-1 RNA levels in human gastric cancer tissues. A negative
      correlation with nodal metastasis.
AB  - BACKGROUND: Gene expression of nm23 has been investigated in number of tumors,
      including breast cancer, colon cancer, malignant melanoma, and hepatocellular
      carcinoma. Its down-regulation has been shown to be associated with metastasis or
      disease progression in some of the tumors. METHODS: nm23 H-1 mRNA levels were
      investigated in 31 surgically resected specimens of gastric cancer by Northern
      blot analysis, and association with clinical stages was determined. RESULTS:
      There was no significant difference in nm23 expression between tumor and matching
      normal mucosa. There was a significant down-regulation of the nm23 gene in
      gastric cancer with serosal invasion (T3 and T4 by the TNM classification) and
      nodal metastasis (pN1 and pN2), although the association of the down-regulation
      with clinically manifest hepatic or peritoneal metastasis was not significant.
      The tumors with low nm23 expression were associated with a poor prognosis.
      CONCLUSIONS: It was suggested that the down-regulation of nm23 gene might have a
      role in metastasis and invasion in gastric cancer, possibly leading to a poor
      prognosis.

PMID- 8293387
TI  - Tripartite differentiation in a carcinoma of the duodenum.
AB  - BACKGROUND: Carcinomas containing three distinctly different cell lines have been
      encountered in the colon and rectum, but a tripartite malignancy in the small
      intestine has not been reported previously. METHODS: A duodenal carcinoma was
      studied by light and electron microscopic examination and immunohistochemistry.
      RESULTS: The duodenal carcinoma was found to have tripartite glandular, squamous,
      and neuroendocrine differentiation. Histologically, an adenocarcinoma, which
      originated in a villous adenoma, was continuous with squamous cell carcinoma and
      small cell carcinoma components. Tumor cells of the squamous cell carcinoma
      component had conspicuous intercellular bridges but did not form keratin pearls.
      Immunohistochemical analysis showed strong expression of carcinoembryonic antigen
      (CEA) by the adenocarcinomatous component. The squamous cell carcinoma component
      demonstrated focal weak CEA and neuron specific enolase (NSE) reactivity.
      Ultrastructurally, tumor cells of this component had frequent desmosomes and free
      tonofilaments. The small cell carcinoma had clusters of dense core granules in
      tumor cell cytoplasmic processes, which are indicative of neuroendocrine
      differentiation. This neuroendocrine component was immunoreactive for
      somatostatin and NSE. CONCLUSIONS: This case of tripartite duodenal carcinoma
      supports the theory of an origin from an intestinal pluripotential stem cell
      capable of differentiating into multiple cell types.

PMID- 8293388
TI  - Preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation
      therapy for rectal cancer.
AB  - BACKGROUND: A Phase I trial was performed to determine the maximum tolerated dose
      of concurrent preoperative radiation therapy (5040 cGy) and 2 cycles (bolus daily
      times 5) of 5-fluorouracil (5-FU) and low-dose leucovorin (LV) (20 mg/m2),
      followed by surgery and 10 cycles of postoperative 5-FU/LV in patients with
      primary or recurrent rectal cancer. METHODS: Twenty-four patients were entered
      into the study. Preoperatively, the initial dose of 5-FU was 325 mg/m2. 5-FU was
      escalated 50 mg/m2, while the dose of LV and radiation therapy remained constant.
      Chemotherapy and radiation began concurrently on day 1. The postoperative
      chemotherapy was not dose escalated; 5-FU, 425 mg/m2, and LV, 20 mg/m2. The
      median follow-up was 10 months (range, 4-19 months). RESULTS: The resectability
      rate with negative margins in the 23 patients who underwent surgery was 100%. One
      patient refused surgery. The pathologic complete response rate was 13% (3 of 23).
      An additional four patients had negative nodes and a microscopic foci of tumor in
      the bowel wall. Therefore, the total clinical complete response rate was 30% (7
      of 23). The maximum tolerated dose of 5-FU for the preoperative combined modality
      segment was 375 mg/m2; therefore, the recommended Phase II dose level is 325
      mg/m2. The incidence of Grade 3+ toxicity for the 22 patients treated at the
      recommended 5-FU dose level (325 mg/m2) during the preoperative combined modality
      segment was as follows: diarrhea, 14%; erythema, 5%; hematologic, 10%; and total,
      18%. The median nadir counts were leukocyte count, 3.7 (range, 1.5-5.9);
      hemoglobin count, 12.2 (range, 10.2-14.3); and platelet count (times 1000), 165
      (range, 92-237). CONCLUSIONS: With this regimen, the recommended doses of
      chemotherapy in the combined modality segment are slightly higher than those
      recommended in arm 2 of the Intergroup postoperative adjuvant rectal trial 0114.
      This regimen will serve both as the preoperative arm of the Intergroup randomized
      trial of preoperative versus postoperative combined modality therapy for
      resectable rectal cancer (INT R9401) as well as the basis for the combined
      modality segment of NSABP RO-3.

PMID- 8293389
TI  - DNA ploidy pattern in human chronic liver diseases and hepatic nodular lesions.
      Flow cytometric analysis on echo-guided needle liver biopsy.
AB  - BACKGROUND: Significantly elevated fractions of diploid hepatocytes and reduction
      in the polyploid populations have been reported in human and experimentally
      induced hepatocellular carcinomas (HCC). This study was conducted to determine
      how these changes are related to conditions that often precede HCC, such as
      chronic hepatitis, cirrhosis, and premalignant focal nodules in cirrhotic livers.
      METHODS: Ultrasound-guided needle biopsy specimens of the liver were obtained
      from patients with chronic hepatitis, cirrhosis, or ultrasonographically
      diagnosed nodules within cirrhotic livers; biopsy specimens also were taken from
      patients without hepatic disease. DNA flow cytometry was performed on isolated
      nuclei to determine the percentages of diploid, tetraploid, and octaploid
      hepatocytes; the S-phase fraction for each diploid peak and the diploid/polyploid
      (tetraploid + octaploid) ratio also were calculated. Part of each specimen was
      reserved for evaluation of hepatocyte binuclearity. RESULTS: Chronically
      hepatitic (18 patients) and cirrhotic (18 patients) livers showed significantly
      increased diploid/polyploid ratios, with respect to normal livers, that were
      significantly correlated with decreases in hepatocyte binuclearity. This trend
      was even more marked in euploid nodules (4 premalignant and 5 malignant), in
      which the S-phase fractions were significantly higher than those of normal liver;
      aneuploidy was found in 6 of 11 malignant and 2 of 6 premalignant nodules.

PMID- 8293390
TI  - Nucleolar organizer regions in small nodular lesions representing early stages of
      human hepatocarcinogenesis.
AB  - BACKGROUND: It is believed that in the early stages of hepatocarcinogenesis, some
      adenomatous hyperplasias (AH) progress to early hepatocellular carcinoma (eHCC),
      and that many eHCC develop into overt hepatocellular carcinoma (HCC) through
      nodule-in-nodule formation. However, the proliferative activity of these small
      nodular lesions has not been fully investigated. METHODS: Cell proliferative
      activity was assessed by counting nucleolar organizer region-associated proteins
      (Ag-NOR) in paraffin sections of 12 AH nodules, 25 eHCC nodules, and 8 nodule-in
      nodule lesions. In nodule-in-nodule lesions, an area of well-differentiated HCC
      corresponding to eHCC and a discrete inner nodule area composed of obvious HCC
      were examined. RESULTS: Mean Ag-NOR numbers of extranodular parenchyma, AH, and
      eHCC were 1.35, 1.35, and 1.75 (P < 0.01), respectively. With regard to the
      relative Ag-NOR number compared with that of parenchyma, there was no overlap
      between AH and eHCC with a border of 1.1-fold except in one specimen. In nodule
      in-nodule lesions, the mean Ag-NOR number (2.53) in the inner nodular area was
      much higher (P < 0.01) than that of the area of eHCC (mean, 1.88). CONCLUSIONS: A
      stepwise increment of Ag-NOR number was demonstrated in accordance with the
      multistep of the AH to eHCC to nodule-in-nodule lesion sequence of
      hepatocarcinogenesis. Thus, it was proposed that the Ag-NOR count may be a
      practical and objective parameter for assessing the malignant potential of
      hepatocellular neoplasms histopathologically.

PMID- 8293391
TI  - Ultrasound-guided percutaneous alcohol injection of small liver metastases.
      Results in 40 patients.
AB  - BACKGROUND: Ultrasound-guided percutaneous alcohol injection (PAI) is used in the
      treatment of hepatocellular carcinoma. The aim of this study is to evaluate the
      results of treatment with PAI of liver metastases (LM) that measure fewer than 5
      cm in diameter, where three or less lesions are present. METHODS: Between
      December 1987 and November 1992, 40 patients were treated for one or more liver
      tumors (n < or = 3). These 40 patients had a total of 55 lesions. There were 55
      LM: 32 cases of colorectal origin, 9 cases of mammary origin, 5 cases with a
      carcinoid tumor, 4 with an undifferentiated tumor, 3 with cancer of the uterus, 1
      with an epidermoid cancer of the esophagus, and 1 with a bronchogenic carcinoma.
      The tumor has been considered spherical and the total volume of alcohol used
      depends on the diameter of the tumor. The volume was calculated using the formula
      V = 4/3 pi [r + 0.5]3; this volume was injected during several sessions, not more
      than 10 ml per injection. The injections were performed once a week until the
      calculated volume was reached. RESULTS: Of the 55 tumors treated, there was a
      complete necrosis in 31 cases (56.3%). The median survival of the 40 patients was
      21 months, with a 3-year actuarial survival of 39%. Among patients with LM of
      colorectal origin, the median survival was increased when the total necrosis was
      obtained (38 months versus 21 months, P < 0.04). CONCLUSION: PAI seems to be a
      therapeutic alterative when surgery is contraindicated or when LM are resistant
      to chemotherapy.

PMID- 8293392
TI  - Multiple hepatic hemangiomas with significant arterioportal venous shunting.
AB  - A patient with multiple hepatic hemangiomas and significant arterioportal
      shunting who was successfully treated by a left-hepatic lobectomy is presented
      herein. In hemangiomas with significant arterioportal venous shunting, it is
      essential to differentiate between hepatocellular carcinoma and hypervascular
      metastatic tumors because few typical findings of hemangioma can be recognized.
      Moreover, an increased hepatic arterial flow can increase the risk of spontaneous
      rupture as well as portal hypertension due to the increased inflow to the portal
      vein. Therefore, a definitive diagnosis should be made by liver biopsy when
      imaging alone is not sufficient to rule out malignancy. Furthermore, hepatic
      resection for hemangiomas with significant arterioportal venous shunting may be
      indicated due to the higher risk of rupture and the possibility of progressive
      portal hypertension.

PMID- 8293393
TI  - Pharmacokinetics of intrapleural recombinant interleukin-2 in immunotherapy for
      malignant pleural effusion.
AB  - BACKGROUND: The authors measured pharmacokinetic parameters before, during, and
      after immunotherapy by continuous intrapleural infusion of recombinant
      interleukin-2 (rIL-2) and correlated the resulting data with clinical effects in
      nine patients with malignant pleural effusion. METHODS: The underlying disease
      was malignant mesothelioma in five patients and adenocarcinoma in four patients.
      Continuous intrapleural infusion of rIL-2 was performed for 5 days at 21 x 10(6)
      IU/m2/day. Maximum tolerated dose previously was determined to be 24 x 10(6)
      IU/m2/day in a Phase I study. Peak levels, the areas under the concentration
      curve (AUC), and drug half-lives were measured in pleural fluid and plasma
      samples collected at 0 (baseline), 12, 24, 48, 72, 96, and 120 hours during
      infusion and at 2, 6, 8, 32, 44, 56, 80, and 120 hours after the end of infusion.
      RESULTS: High and prolonged intracavitary drug levels were achieved in all but
      two patients, with a statistically significant correlation between peak values
      and AUC. Four patients achieved objective responses according to World Health
      Organization criteria. Neither of the patients with undetectable rIL-2 levels had
      response to therapy. Serum rIL-2 levels were low regardless intrapleural levels.
      Mean AUC was lower in the plasma than in the pleural fluid. CONCLUSIONS: This
      study demonstrates that continuous intrapleural infusion of rIL-2 is an active
      method of treatment for malignant pleural effusion. The low serum levels
      associated with this method greatly improve tolerance. The results also indicate
      that the concentration and duration of intrapleural rIL-2 levels may depend on
      the extent of pleural invasion. Additional study is needed to confirm this
      finding.

PMID- 8293394
TI  - Bone marrow dysplasia in patients with newly diagnosed acute myelogenous leukemia
      does not correlate with history of myelodysplasia or with remission rate and
      survival.
AB  - BACKGROUND: The records and initial bone marrow studies of 106 patients with
      newly diagnosed acute myelogenous leukemia (AML) were analyzed retrospectively to
      determine whether bone marrow dysplasia was predictive of a previous
      myelodysplastic disorder or correlated with remission rate and survival. METHODS:
      Bone marrow aspirates and biopsy specimens were reviewed in a blinded fashion;
      dysplasia was assessed in as objective a manner as possible by numerically
      scoring nine specific findings: erythrocyte multinuclearity, nuclear
      fragmentation, megaloblastic characteristics, leukocyte granulation abnormalities
      and nuclear malformations, Pelger-Huet cells, and megakaryocytic dysplasia
      (mononuclear megakaryocytes, micromegakaryocytes, and megakaryocytes with
      multiple distinct nuclei). RESULTS: Dysplasia of the megakaryocytic line was seen
      in 34% of patients; 70% of the patients had erythrocyte dysplasia; and 68% had
      leukocyte dysplasia. Pelger-Huet cells were seen in bone marrow of 35% of the
      patients. Overall dysplasia score and specific dysplastic findings such as Pelger
      Huet cells did not correlate with a known history of myelodysplasia (P = 0.47),
      cytogenetic abnormalities (P = 0.35), prior chemotherapy treatment with or
      without alkylating agents (P = 1.00), previous malignant disorders such as
      polycythemia vera (P = 1.00), remission rate (P = 0.93), or survival (P = 0.42).
      Multivariate analysis confirmed known independent risk factors for remission in
      this patient population, including age (P = 0.04), history of prior chemotherapy
      (P = 0.04), abnormalities in chromosomes 5, 7, or 8 (P = 0.02), and type of
      antileukemia therapy (P < 0.001). CONCLUSIONS: Bone marrow dysplasia is common in
      patients with AML and does not correlate with a history of myelodysplasia or
      predict outcome when patients are treated with standard intensive AML therapy.

PMID- 8293395
TI  - Serum deoxythymidine kinase in myelodysplastic syndromes.
AB  - BACKGROUND: Previous studies have shown that serum levels of deoxythymidine
      kinase (sTK) provide useful prognostic information in various malignancies, such
      as Hodgkin's disease, non-Hodgkin's lymphomas, multiple myeloma, and acute
      myeloid leukemia (AML). METHODS: Using a radioenzyme assay, the authors
      determined sTK in 146 patients with primary myelodysplastic syndromes (MDS).
      Morphologic subtypes were refractory anemia (RA) in 18 patients, RA with ring
      sideroblasts (RARS) in 24, RA with excess of blasts (RAEB) in 41, RAEB in
      transformation (RAEB/T) in 29, and chronic myelomonocytic leukemia (CMML) in 34.
      RESULTS: Enzyme levels ranged from 1.1 to 829 U/microliters. One hundred fifteen
      (79%) patients had elevated sTK levels (more than 5 U/microliters) at the time of
      diagnosis. In advanced stages of MDS (RAEB, CMML, and RAEB/T) enzyme activities
      were higher than in early stages (RA and RARS) (P < 0.05). However, sTK levels
      were not correlated with the percentage of medullary blast cells. Among other
      parameters tested, the best correlation with sTK was found for serum lactate
      dehydrogenase (LDH) activity (r = 0.29; P < 0.0005). As shown by life table
      analysis, sTK activity at diagnosis provided useful information regarding the
      prognosis of patients. For patients with sTK levels of less than 10
      U/microliters, actuarial survival after 2 years was 65%, compared with 33% for
      those with enzyme values of 10 U/microliters or greater. The 5-year cumulative
      survival rates were 34% and 14%, respectively (P < 0.0005). However, sTK levels
      at diagnosis were not useful for predicting transformation to AML. Nine of 61
      (15%) patients with sTK of less than 10 U/microliters had AML develop, whereas 15
      of 57 (26%) patients with sTK of 10 U/microliters or greater had disease progress
      to acute leukemia (chi-square, 1.64; P = 0.2). CONCLUSIONS: Considering the lack
      of correlation with bone marrow blasts, the authors conclude that increased sTK
      levels in MDS are primarily attributable to intramedullary destruction of
      hematopoietic precursors and do not reflect the leukemic blast cell burden. This
      appears similar to the ineffective hematopoiesis of vitamin B12 deficiency, which
      is associated with elevated levels of sTK and LDH. The data suggest that sTK is a
      prognostic parameter that can be used to predict the survival of patients with
      MDS. However, multivariate analysis shows that the predictive value of sTK is not
      superior to that of LDH.

PMID- 8293396
TI  - Metastatic basal cell carcinoma. Report of five cases.
AB  - BACKGROUND: Metastatic basal cell carcinoma (MBCC) is rare. Risk factors for the
      development of MBCC include a history of persistent basal cell carcinoma (BCC)
      for many years, refractory to conventional methods of treatment and previous
      radiation treatment either in early adulthood or for localized cancer. Most MBCC
      originate from large tumors. METHODS: The authors report five patients with basal
      cell carcinomas (BCC) of the ear (two patients), scalp, inner canthus, and
      nasolabial fold that metastasized to the regional lymph nodes, skin, and
      submandibular gland. In addition, the authors reviewed more than 40 reports of
      MBCC (n = 65) from 1981 to 1991 and tabulated the primary tumors by size and
      depth of invasion according to TNM classification, a classification that
      previously has not been used for BCC. RESULTS: The authors tabulated the size
      distribution of tumors of 45 patients with MBCC. The overall mean and median
      diameters of the primary BCC were 8.7 and 7.0 cm, respectively. The mean area of
      the primary MBCC lesion that originated on the face and trunk was 62 and 217 cm2,
      respectively. Using the TNM classification, approximately 9% of MBCC originate
      from tumors smaller than 10 cm2. In addition, the authors found that large (T2
      and T3) and deep (T4) BCC account for approximately 75% of the metastatic tumors.
      Metastatic BCC from primary tumors smaller than 1 cm in diameter are
      exceptionally rare. CONCLUSIONS: Approximately 67% of MBCC (n = 238) originate
      from facial sites. Using the data base of the Mohs Surgery Clinic, the authors
      found that BCC greater than 3 cm in diameter have approximately a 1.9% incidence
      of metastasis, and the overall rate of metastases for morpheaform BCC is less
      than 1%. Patients with tumors classified as T3 and T4 lesions ideally should be
      followed up for 10 or more years for the remote possibility of the development of
      MBCC.

PMID- 8293397
TI  - Application of multistage Markov modeling to malignant melanoma progression.
AB  - BACKGROUND: A fundamental research goal in clinical melanoma studies is to
      understand the natural history of melanoma and its relationship with prognostic
      factors. The current understanding of melanoma progression and the relationship
      of risk factors is based on two-stage modeling. METHODS: The authors propose a
      multistage Markov model for melanoma progression. This model is applied to a data
      set consisting of approximately 3900 follow-up staging visits of patients with
      melanoma. The approach takes into account the heavy censoring encountered in this
      data set and all chronic, subclinically progressive disease. The Markov
      transition parameters are expressed as Cox regression functions of the relevant
      prognostic variables. Parameter estimation is achieved by using a missing-data
      approach. RESULTS: Tumor thickness, level, and site and patient gender and age at
      diagnosis are independent risk factors in the transition from local to nodal
      disease. Tumor thickness and level of invasion and patient age are factors in the
      transition from local disease to dissemination (without intervening involvement
      of the nodes). Tumor thickness, patient age, primary site, and the number of
      involved lymph nodes are factors in the transition from nodal disease to
      dissemination. Transition from dissemination to death is affected by primary
      thickness, patient gender, number of nodes involved, and site of metastases.
      CONCLUSION: This multistage analysis contributes to a more accurate understanding
      of the progress of melanoma and is likely to be applicable to the study of other
      progressive diseases. Graphic goodness-of-fit results suggest satisfactory
      predictability of the model to other data sets.

PMID- 8293398
TI  - Interaction of transforming growth factor-alpha and epidermal growth factor
      receptor in breast carcinoma. An immunohistologic study.
AB  - BACKGROUND: Interaction of transforming growth factor-alpha (TGF-alpha) with its
      receptor, epidermal growth factor receptor (EGFR), has been implicated as an
      autoregulatory autocrine mechanism of breast epithelial proliferation. METHODS:
      To examine the interrelationship and clinical relevance of TGF-alpha and EGFR in
      breast carcinoma, methanol-fixed cryostat sections from 73 patients were
      immunostained with monoclonal antibodies to epidermal growth factor (EGF), EGFR,
      and TGF-alpha. RESULTS: Neither EGFR nor TGF-alpha staining was diagnostic or
      specific for the detection of malignant neoplastic cells. Both exhibited staining
      along the basal lamina of most benign ducts and lobules. TGF-alpha staining was
      observed in neoplastic cells in 41% and in non-neoplastic cells (peritumoral
      stroma and benign duct/lobular epithelium) in 36% of patients. Staining for EGF
      and TGF-alpha failed to correlate with node status or grade; however, TGF-alpha
      negative tumors were more frequently positive for estrogen receptor (ER) (70%
      versus 14%; P = 0.03). The presence of EGFR correlated with positive lymph node
      status (P = 0.004), poor differentiation (P = 0.001), and negative ER status (P =
      0.0001). EGFR staining was more common in neoplasms which recurred, but this
      approached significance only in the group with node-negative disease (mean follow
      up, 52 months; P = 0.06), and neoplastic cell TGF-alpha correlated with disease
      recurrence in patients with node-positive disease (no recurrence, -13% positive
      versus recurrence, -52% positive; P = 0.01). Concurrent TGF-alpha/EGFR staining,
      present in 18% of tumors, also was predictive of disease recurrence (no
      recurrence, 3% positive for both versus recurrence, 31% positive for both, P =
      0.03). CONCLUSIONS: TGF-alpha is heterogeneously expressed in neoplastic and host
      derived components of breast tumors. Concurrent EGFR/TGF-alpha immunostaining may
      characterize a clinically aggressive subset of breast carcinomas, possibly
      reflecting autocrine interaction, and conferring growth advantage or metastatic
      phenotype.

PMID- 8293399
TI  - Predictors of axillary lymph node metastases in patients with T1 breast cancer. A
      multivariate analysis.
AB  - BACKGROUND: In T1 tumors, the reported incidence of lymph node metastases ranges
      from 21% to 35%. The authors analyzed the pathology parameters of T1 tumors for
      their association with the likelihood of axillary lymph node metastases. METHODS:
      Two hundred sixty-three patients with T1 unilateral invasive breast cancer were
      studied. All underwent axillary dissection, and the pathologic status of the
      nodes was known. The parameters of the primary tumor evaluated included size,
      histologic subtype, nuclear grade, DNA ploidy, S-phase fraction (SPF), hormone
      receptor status, lymphatic/vascular invasion (LVI), and host reaction. RESULTS:
      Seventy-two (27%) patients had nodes that were positive for metastasis.
      Univariate analysis showed that lymph node metastases were associated with tumors
      larger than 1 cm (P = 0.001), moderate or poorly differentiated nuclear grade (P
      = 0.005), high SPF (P = 0.041), presence of LVI (P < 0.001) and patients younger
      than 60 years (P = 0.01). However, independent predictors of lymph node
      metastasis in the multivariate logistic regression analyses were tumor size and
      LVI. Twenty-five patients had tumors larger than 1.0 cm and presence of LVI; of
      these, 17 (68%) had lymph node metastases. Of the 79 patients who had neither of
      these features, only 7 (9%) had lymph node metastases. CONCLUSIONS: The authors
      conclude that characteristics of the primary tumor can help assess the risk for
      axillary lymph node metastases. Selected patients who are assessed to be at
      minimal risk might be spared routine axillary dissection or radiation therapy to
      the axilla.

PMID- 8293400
TI  - Hormonal treatment for metastatic breast cancer. An Eastern Cooperative Oncology
      Group Phase III trial comparing aminoglutethimide to tamoxifen.
AB  - BACKGROUND: Tamoxifen and aminoglutethimide are two hormone therapies reported to
      be effective palliative approaches for patients with metastatic breast cancer.
      The current trial was designed to evaluate their relative therapeutic
      effectiveness. METHODS: Two hundred forty-nine postmenopausal women with advanced
      breast cancer were randomized in an Eastern Cooperative Oncology Group (ECOG)
      Phase III study to treatment with adrenalectomy, aminoglutethimide, or tamoxifen
      with crossover to alternate therapy if disease progressed. Adrenalectomy was
      dropped as a treatment after 2 years because of low patient accrual. RESULTS:
      There were 216 evaluable patients entered in the study with 108 initially
      randomized to aminoglutethimide and 108 to receive tamoxifen therapy. The overall
      response rate for aminoglutethimide was 45%, and for tamoxifen it was 27%. One
      institution had a response rate of 60% with aminoglutethimide and only 4% with
      tamoxifen, whereas all of the other institutions combined had a response rate of
      41% with aminoglutethimide and 34% with tamoxifen. Eighty-seven evaluable
      patients crossed over to the other drug (44 to aminoglutethimide and 43 to
      tamoxifen). There was a 36% response rate to aminoglutethimide and 19% to
      tamoxifen, with stable disease in 36% of both groups. The overall survival rates
      were identical. Toxicity was greater with aminoglutethimide (dermatitis) but was
      not life-threatening. Glucocorticoid support with either dexamethasone or
      hydrocortisone was acceptable. CONCLUSIONS: Both aminoglutethimide and tamoxifen
      produced responses in postmenopausal patients with breast cancer, and a
      significant number of crossover responses were observed. Of interest in this
      randomized study was the observation that one institution had a markedly
      different response rate on induction, reinforcing the need for multi-institution
      trials in Phase III studies.

PMID- 8293401
TI  - Induction chemotherapy followed by breast conservation for locally advanced
      carcinoma of the breast.
AB  - BACKGROUND: Few women with locally advanced breast cancer remain disease-free,
      even for 2 years. Response to induction chemotherapy may be associated with
      longer disease-free and overall survival rates. The role of breast conservation
      in selected patients with response to induction chemotherapy was evaluated.
      METHODS: Since 1979, patients with Stages IIB and III breast cancer have
      undergone induction chemotherapy; patients with response continued chemotherapy
      until a plateau of regression was achieved. Before 1983, all patients having a
      response to chemotherapy underwent mastectomy; since 1983, selected patients have
      undergone breast conservation. Outcomes were tallied comparing these two groups
      of patients. RESULTS: The study group included 189 women, who were followed up
      for 12-159 months (median, 46 months) after diagnosis. Of the patients, 85% had a
      response to induction chemotherapy. Patients with no response were excluded from
      additional consideration in this study. One hundred three (64%) women underwent
      mastectomy; 55 (36%) were treated with breast conservation. The disease-free 5
      year survival rate was 61% for all patients with a response to chemotherapy; 56%
      for those having mastectomy and 77% for those having breast conservation. The
      overall 5-year survival rate was 69% for all patients with a response to
      chemotherapy, 67% for those undergoing mastectomy and 80% for those having breast
      conservation. CONCLUSIONS: Induction chemotherapy achieves significant tumor
      regression in most women with locally advanced breast cancer, permitting
      subsequent breast conservation or mastectomy with a greater expectation of long
      term success. Breast conservation is used more frequently with the same
      expectation of success as mastectomy, presuming careful selection based on
      response to chemotherapy.

PMID- 8293402
TI  - Prognostic utility of epidermal growth factor receptor overexpression in
      endometrial adenocarcinoma.
AB  - BACKGROUND: Overexpression of epidermal growth factor receptor (EGFR) has been
      reported in endometrial adenocarcinoma. METHODS: A retrospective analytic study
      was designed to investigate its prognostic utility. Sixty-nine patients were
      studied with cell types that included endometrioid (n = 45), papillary serous (n
      = 16), and clear cell (n = 8). Patients' medical charts and survival data were
      reviewed. Assessment of EGFR overexpression was done at the protein level by the
      use of an anti-EGFR polyclonal antibody that reacts with the cytoplasmic membrane
      glycoprotein receptor in paraffin-embedded tissues. RESULTS: EGFR was
      overexpressed in 34 (49%) patients in whom immunoreactivity was limited to
      neoplastic cells. Initial bivariate analysis revealed significant correlations
      between EGFR immunoreactivity and histologic grade (r = 0.44, P < 0.001),
      metastasis (r = 0.38, P < 0.001), cell type (r = 0.30, P < 0.01), myometrial
      invasion (r = 0.30, P < 0.01), and patient age (r = 0.30, P < 0.01). Multiple
      logistic regression analyses showed that EGFR overexpression and nonendometrioid
      cell types are two independent statistically significant markers for the presence
      of metastases. EGFR immunoreactivity can significantly predict myometrial
      invasion, but after controlling for the histologic grade, its ability of
      significantly predict invasion was lost. EGFR overexpression was shown to be a
      statistically significant predictor of survival, even after controlling for
      patient age, histologic grade, and cell type. CONCLUSIONS: Expression of this
      oncoprotein may serve as an independent prognostic indicator and a guide to
      therapy in patients with endometrial cancer.

PMID- 8293403
TI  - National survey of ovarian carcinoma. IV: Patterns of care and related survival
      for older patients.
AB  - BACKGROUND: An analysis was conducted by the American College of Surgeons Cancer
      Commission evaluating the patterns of care of ovarian cancer patients diagnosed
      in 1983 and 1988. The purpose of this study was to investigate whether there was
      a difference in the care patterns of elderly ovarian cancer patients and its
      impact on survival. METHODS: Data were collected from 25 consecutive patients
      whose disease was diagnosed initially at 904 participating hospitals with cancer
      programs in 1983 and 1988. The survival and care of patients greater than or
      equal to 80 years of age were compared to those less than 80 years of age.
      RESULTS: Of the 12,316 patients evaluated, 1,115 were 80 years or older. A
      significant reduction in survival was noted among patients 80 years and older as
      compared to their younger counterparts (P = 0.03-0.00001). The 5-year survivals
      were: stage I, 89% versus 79%; stage II, 58% versus 40%; stage III, 25% versus
      11%; and stage IV, 13% versus 3%, respectively, for those less than 80 years old
      as compared to those greater than or equal to 80 years old. Most elderly ovarian
      cancer patients were cared for by nononcologists such as general surgeons (31%)
      and obstetricians/gynecologists (29%). As a group, older patients had fewer total
      abdominal hysterectomies, bilateral salpingo-oophorectomies, and omentectomies
      than their younger counterpart (P < 0.00001). As further evidence for a less
      aggressive surgical approach, the optimal tumor debulking rates of women greater
      than or equal to 80 years were significantly less than those of younger patients
      (P < 0.001). There was no significant increase in anesthesia complications
      between age groups. Generally, older patients are less likely to receive adjuvant
      chemotherapy than younger patients (42% versus 69%, P < 0.0001). CONCLUSION: It
      appears that conservative treatments contributed to the decreased survival of
      older ovarian cancer patients.

PMID- 8293404
TI  - Adjuvant irradiation after prostatectomy for carcinoma of the prostate with
      positive surgical margins.
AB  - BACKGROUND: Patients with adenocarcinoma of the prostate treated with
      prostatectomy who have tumor at the margins of the surgical specimen or tumor
      involvement of the seminal vesicles have a high risk of local recurrence and
      metastatic disease. It is unclear whether postoperative irradiation improves
      their outcome. METHODS: This is a retrospective analysis of patients treated with
      prostatectomy for adenocarcinoma of the prostate who had surgical margins or
      seminal vesicles involved by tumor. Thirty-four patients received adjuvant
      postoperative irradiation (Group 1), and 43 patients did not receive irradiation
      (Group 2). RESULTS: The tumor control rates in the prostatic bed for patients who
      had radical prostatectomy were 100% and 84% in Groups 1 and 2, respectively (P =
      0.017). Actuarial 10-year disease-free survival from the date of prostatectomy
      was 46% and 55% for Groups 1 and 2, respectively. CONCLUSIONS: Adjuvant
      irradiation after prostatectomy in patients with positive surgical margins or
      seminal vesical invasion increases prostatic bed local tumor control but does not
      affect survival. Postoperative irradiation is associated with acceptable
      morbidity.

PMID- 8293405
TI  - Testicular cancer in blacks. A multicenter experience.
AB  - BACKGROUND: The rarity of testis tumor in black patients has made the study of a
      large series difficult. Much of the epidemiologic and clinical information
      regarding this neoplasm in this population is in dispute, including data on
      incidence, prognosis, histologic distribution, age and stage at presentation, and
      side distribution. METHODS: A retrospective review of 66 blacks with testicular
      tumors from seven military medical centers was performed. RESULTS: Similar
      results were found for blacks with testis tumor to those of the general testis
      cancer population regarding prognosis, side distribution, and age of onset for
      nonseminoma and interstitial tumors. There is a slight increase in the expected
      number of interstitial tumors in blacks, but the distribution between seminoma
      and nonseminoma is similar to the general population. The mean age of
      presentation for seminoma in blacks was younger than that of the general testis
      cancer population. For testis tumor treated at the same institution, there was an
      increased delay of diagnosis in blacks compared with whites. The number of new
      cases of testicular cancer between 1979 and 1991 at one major center was
      increased for whites but not for blacks. The availability of cisplatin-based
      combination chemotherapy has resulted in an improved prognosis for blacks, as has
      already been demonstrated for white populations. CONCLUSIONS: Testis tumor in
      blacks behaves similarly to testis tumor in the general population except that in
      blacks there are more interstitial tumors and the mean age of presentation for
      seminoma is younger. Further, there is an increased delay in diagnosis for blacks
      compared with whites, but the incidence of this tumor in this population does not
      appear to be increasing. Cisplatin-based chemotherapy has significantly improved
      survival in this population.

PMID- 8293406
TI  - Serum tissue polypeptide antigen (S-TPA) in bladder cancer as a tumor marker. A
      prospective study.
AB  - BACKGROUND: Tissue polypeptide antigen (TPA) is a differentiation and a
      proliferation tissue marker of non-squamous epithelia. Increased urinary and
      serum TPA (S-TPA) levels were found in some patients with invasive bladder
      cancer. The authors report the results of a prospective study evaluating the role
      of serum TPA (S-TPA) in bladder carcinoma. METHODS: S-TPA concentrations were
      measured by radioimmunoassay in 53 patients with invasive bladder tumor before
      treatment, at the end of treatment, and during follow-up. The upper normal limit
      of the test was set at 80 UI/ml. RESULTS: With a specificity of 100%, the
      diagnostic sensitivity of the test was 54.7%. S-TPA was increased in 88% of
      patients with N1 + N2 disease compared with 38.8% of the patients with N0 disease
      (P = 0.01) and in 100% of patients with metastatic disease and 48% of patients
      with nonmetastatic disease (P = 0.01). S-TPA was increased in 23% of patients
      with total macroscopic debulking and in 68% of patients with persistent
      macroscopic disease (P = 0.004). For patients staged N0 M0, no statistical
      correlation between S-TPA level and debulking by transurethral resection (TUR)
      was found (P = 0.15). In the subset of patients with normal pretherapeutic S-TPA
      levels, 75% achieved a complete response, compared with 44.8% of the patients
      with initial elevated S-TPA levels (P = 0.04). However, there was no
      statistically significant relationship between pretherapeutic S-TPA levels and
      immediate response to treatment according to the stratification for tumor volume
      after initial debulking by TUR. For a mean follow-up of 15 months +/- 7 months,
      median survival time and 1-year survival rates were studied in the subset of
      patients with limited disease (N0 M0) according to the pretherapeutic S-TPA
      levels. The median survival time was not reached, and the 1-year survival rate
      was 80% when the initial S-TPA level was normal; these were 10 months and 44%,
      respectively, when the S-TPA level was high (P < 0.01). Among the 31 patients who
      achieved a complete response, 9 experienced a relapse, with an increase of the S
      TPA level in 8 patients. CONCLUSIONS: The S-TPA level is correlated with initial
      tumor volume. It appears to be a prognostic factor and a valuable parameter for
      follow-up.

PMID- 8293407
TI  - Mesenchymal chondrosarcoma of the orbit. Report of three new cases and review of
      the literature.
AB  - BACKGROUND: Extraskeletal mesenchymal chondrosarcoma is a rare tumor
      characterized by undifferentiated mesenchymal cells with islands of mature
      hyaline cartilage. Considering all sites, long-term survival is approximately
      30%. Only seven cases of orbital mesenchymal chondrosarcoma have been reported.
      METHODS: The records of three cases of orbital mesenchymal chondrosarcoma treated
      at the Columbia-Presbyterian Medical Center, and the seven previously reported
      cases of this tumor were reviewed to determine clinical characteristics and
      appropriate therapy. RESULTS: Nine of the 10 patients were female; age of onset
      ranged from 10 to 35 years. Of eight patients with at least 2 years of
      observation, five survived 5 or more years after resection, or after resection
      plus adjuvant therapy. Two patients died of metastatic disease 2 and 5 years,
      respectively, after the initial treatment, and one died of pneumonia 6 months
      after surgery. Review of the histology of the three cases treated at Columbia
      Presbyterian Medical Center did not identify distinct histologic types that might
      guide therapy. Presenting symptoms were typical of symptoms of an orbital mass:
      proptosis, pain, diplopia, change in visual acuity, ptosis, and tearing.
      CONCLUSION: The small number of reported cases of mesenchymal chondrosarcoma of
      the orbit prevents definitive conclusions, but it appears that resection is
      adequate therapy in some cases. Extraskeletal mesenchymal chondrosarcoma of the
      orbit may have a better prognosis than tumors in other sites.

PMID- 8293408
TI  - Pattern of mutant p53 expression in human astrocytomas suggests the existence of
      alternate pathways of tumorigenesis.
AB  - BACKGROUND: Clinical observations suggest that malignant astrocytomas may arise
      from well-differentiated, low-grade tumors that have undergone anaplastic
      progression or may develop de novo. Mutations that alter the function of the p53
      gene product are thought to play a critical role in astrocytoma tumorigenesis.
      The authors studied the pattern of mutant p53 expression in astrocytomas to
      define its role in the formation of malignant tumors by these different pathways.
      METHODS: Tissues from 44 astrocytomas corresponding to Grades I-IV of the World
      Health Organization (WHO) classification were analyzed for the presence of
      mutations in exons 5, 7, and 8 of the p53 gene using single strand conformation
      polymorphism (SSCP) and sequence analysis of DNA amplified by the polymerase
      chain reaction. Immunostaining for mutant p53 proteins was performed on tissues
      fixed in formaldehyde solution and embedded in paraffin; the tissues were from
      these 44 astrocytomas and another 103 astrocytomas obtained from archival
      material. RESULTS: Tumors with mutant p53 genes were reliably identified by
      immunostaining for mutant p53 proteins. A higher percentage of astrocytomas of
      histologic Grades II-IV stained positively for p53 than were identified by
      mutational analysis. The average ages of patients with Grade III/IV astrocytomas
      with prominent (> 10%) p53 staining and those with sparse (< 10%) or no p53
      staining were 44.5, 64.3, and 67.9 years, respectively (P < 0.0001). CONCLUSIONS:
      The pattern of mutant p53 expression is consistent with a role in driving the
      progression of low-grade astrocytomas to more malignant tumors. These results
      provide a genetic basis for the clinical observation that malignant astrocytomas
      resulting from anaplastic progression occur in a younger patient population than
      do malignant astrocytomas arising de novo.

PMID- 8293409
TI  - Papillary and follicular thyroid carcinomas with an insular component.
AB  - BACKGROUND: Papillary (PC) and follicular (FC) thyroid carcinomas may have a
      focal or predominant insular component (IC). This study correlates histologic
      behavior with the extent of the IC of these tumors. METHODS: Forty-one thyroid
      carcinomas (17 follicular variants [FV] of PC, 24 FC) with focal or predominant
      IC were reviewed. The tumors were stained with carcinoembryonic antigen,
      thyroglobulin, and calcitonin. DNA ploidy analysis was done on 18 tumors on
      paraffin-embedded tissue. The IC was correlated with age, stage of disease,
      follow-up, and ploidy analysis by Fisher's exact two-tailed test. RESULTS: No
      tumor was purely insular. IC was minor (10-40% tumor area) in 16 and predominant
      (50-90%) in 25. Nuclear features in IC included typical FC nuclei in 14, FVPC
      nuclei in 16, and intermediate-type nuclei in 16 tumors. Vascular invasion was
      seen in 22, necrosis in 10, and sclerotic stroma in all. Fourteen tumors were
      confined to the thyroid, 13 showed regional spread, and 9 had distant metastases;
      five patients are dead of disease and six are alive with disease. Thirteen tumors
      were diploid, three tetraploid, and two hyperdiploid aneuploid. There was no
      correlation of quantity of IC with tumor stage, follow-up status, or ploidy.
      CONCLUSION: IC within PC and FC does not adversely affect prognosis.

PMID- 8293410
TI  - Follicular variant of papillary thyroid carcinoma. A clinicopathologic study.
AB  - BACKGROUND: A retrospective clinicopathologic study was performed to identify the
      influence of diagnostic and therapeutic procedures on the outcomes of patients
      with the follicular variant of papillary thyroid carcinoma (FVPTC). METHODS: The
      results of 37 patients with FVPTC were compared with those of 37 randomly
      selected patients with papillary carcinoma and 22 patients with follicular
      carcinoma. Diagnostic, therapeutic, and follow-up data were obtained by review of
      clinical and histologic materials. RESULTS: Median follow-up was approximately 3
      years in all groups. Fine-needle aspiration had a sensitivity of 75% for FVPTC,
      which was similar to that for papillary carcinoma. Frozen section evaluation had
      a sensitivity of only 27% for FVPTC but 94% for papillary carcinoma and 44% for
      follicular carcinoma. All patients for whom the fine-needle aspiration specimen
      contained cytologic features of papillary carcinoma and frozen section suggested
      a follicular lesion proved to have FVPTC: Consequently, hemithyroidectomy was
      performed three times more often among patients with FVPTC than among those with
      papillary carcinoma. FVPTC tumors were modestly, but significantly, smaller than
      papillary carcinoma tumors (1.2 versus 1.6 cm). Metastases to cervical lymph
      nodes occurred least often in patients with FVPTC and usually were detected
      within 3 months of diagnosis. The frequency of distant metastases within this
      limited period of follow-up did not differ between FVPTC and papillary carcinoma.
      CONCLUSIONS: Fine-needle aspiration appears to be superior to frozen section for
      identification of FVPTC, although the number of aspirations performed was
      limited. Greater use of aspiration may permit more appropriate surgical
      management of this disease. Local and distant metastases of FVPTC do not occur
      more often than do those of papillary carcinoma.

PMID- 8293411
TI  - Treatment of advanced medullary thyroid carcinoma with a combination of
      cyclophosphamide, vincristine, and dacarbazine.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) is a neoplasm of the parafollicular
      C cells of the thyroid gland, which belongs to the diffuse neuroendocrine system.
      This cancer usually behaves in a relatively indolent manner for most patients.
      However, approximately 20% of patients have a more aggressive course that
      requires effective management. There are few reported clinical trials of
      chemotherapy for MTC. From the literature, the most active agent appears to be
      doxorubicin, with response rates of 30% reported. On the basis of the activity of
      cyclophosphamide, vincristine, and dacarbazine (CVD) in other advanced
      neuroendocrine neoplasms, the authors tested the combination in patients with
      advanced MTC. METHODS: Seven patients with advanced MTC were treated with
      cyclophosphamide (750 mg/m2), vincristine (1.4 mg/m2), and dacarbazine (600 mg/m2
      daily for 2 days in each cycle) every 3 weeks. Assessments of measurable tumor
      and serum calcitonin and carcinoembryonic antigen were made before treatment and
      followed up until progressive disease was documented. RESULTS: Two patients had
      partial tumor and biochemical responses for a duration of 14 and 29 months,
      respectively. One patient had a partial biochemical response and stable tumor
      measurements for 9 months, and another patient had stable tumor size and markers
      for 14 months. Three patients had progressive disease. Diarrhea and flushing
      improved in two patients who had partial biochemical responses. CONCLUSION: Our
      experience suggests that CVD chemotherapy has moderate activity and is well
      tolerated in patients with advanced MTC. Additional prospective studies of this
      regimen for MTC are required.

PMID- 8293412
TI  - A randomized, multicenter study comparing the efficacy and tolerability of
      tropisetron, a new 5-HT3 receptor antagonist, with a metoclopramide-containing
      antiemetic cocktail in the prevention of cisplatin-induced emesis.
AB  - BACKGROUND: Chemotherapy-induced emesis is one of the most disturbing side
      effects in cancer therapy. Thus, antiemetic treatment is a mandatory adjunct in
      emetogenic chemotherapy. METHODS: Tropisetron (Navoban, Sandoz Pharma Ltd.,
      Basel, Switzerland), a new 5-HT3 receptor antagonist, was compared in a
      randomized multicenter trial with a high-dose metoclopramide-dexamethasone
      cocktail for the prevention of nausea and emesis during cisplatin-containing
      chemotherapy. Two hundred fifty-nine chemotherapy-naive patients were included
      and followed during two consecutive courses. The main cancer types were
      gynecologic tumors, followed by lung cancer, head and neck cancer, and bladder
      cancer. The cisplatin dose usually was in the range of 50-89 mg/m2. The efficacy
      and quality of life assessments and the safety recordings were done during the
      first 6 days of both courses of chemotherapy. RESULTS: Acute vomiting was
      prevented in 63-64% of patients by both antiemetic regimens. The total rate of
      control of vomiting increased from 63% on day 1 to 93% on day 6 in the group
      receiving tropisetron. Acute nausea was prevented in 40% of the patients with
      tropisetron monotherapy and in 61% of patients receiving the antiemetic cocktail.
      With regard to delayed nausea, there were no significant differences between the
      two antiemetic regimens. Mild headache and constipation were more frequently
      associated with tropisetron, and extra-pyramidal side effects and sedation were
      associated with the antiemetic cocktail. CONCLUSIONS: Tropisetron was easier to
      administer and better tolerated than the cocktail, and it seems to be a highly
      efficacious and safe new antiemetic drug.

PMID- 8293413
TI  - Primary central nervous system lymphomas. Immunophenotypic, virologic, and
      cytogenetic findings of three patients without immune defects.
AB  - BACKGROUND: Primary central nervous system (PCNS) lymphoma is a relatively rare
      disease, but an increasing incidence is reported. The Epstein-Barr virus (EBV),
      which is often found in lymphomas of immunocompromised patients, has been
      implicated in the development of lymphomas. Many cytogenetic analyses of nodal B
      cell lymphomas have been performed, but few studies on PCNS lymphomas have been
      reported. METHODS: The detection of EBV genome using the polymerase chain
      reaction (PCR) method and cytogenetic studies were performed, in addition to
      histopathologic and immunophenotypic approaches in biopsied tissue from three
      patients with PCNS lymphoma. Immunosuppressive states and exposure to mutagens
      were not clear in all patients. RESULTS: Histopathologic examination disclosed a
      diffuse type of malignant lymphoma in all patients. Immunophenotypic studies
      revealed B cell phenotype in all patients, two of whom showed positive reaction
      for CD5. The PCR method revealed no involvement of EBV genome in tumors in any
      patients. The cytogenetic study showed clonal chromosome abnormalities in all
      patients, and abnormalities of chromosome 1 (1q21), 6 (-6, 6q15 and 6q21), 7 (-7
      and 7p15), and 14 (14q24 and 14q32) were prominent. The t(6;14)(q15;q32) observed
      in Patient 1 is the first case to be reported in human de novo lymphoma.
      CONCLUSIONS: These findings indicate that the causative role of EBV in PCNS
      lymphoma without immune defects is not clear. The cytogenetic findings were
      similar to those observed in nodal B-cell lymphoma, suggesting that the origin of
      PCNS lymphoma cells does not differ from nodal B cell lymphoma cells
      cytogenetically.

PMID- 8293414
TI  - Carcinoembryonic antigen-like reactivity in malignant mesothelioma. A comparison
      between different commercially available antibodies.
AB  - BACKGROUND: Immunohistochemical reactivity to carcinoembryonic antigen (CEA) is
      often used to exclude the diagnosis of malignant mesothelioma. METHODS: In a
      study comprising 61 malignant mesotheliomas and 20 adenocarcinomas, the
      reactivity against one polyclonal and five different monoclonal anti-CEA
      antibodies was tested. RESULTS: Thirteen of the mesotheliomas showed distinct
      reactivity to the polyclonal antiserum, even after absorption with spleen powder.
      Of the monoclonal preparations, those staining granulocytes and macrophages also
      showed varying reactivity to some of these 13 mesotheliomas. Only one monoclonal
      antibody showed no such reactivity and labeled no mesothelioma case, while its
      capacity to stain adenocarcinomas remained. CONCLUSIONS: Mesotheliomas may
      contain substances that share epitopes with the CEA molecule. Only one of the
      tested monoclonal antibodies seemed sufficiently specific to be used
      diagnostically as a single immunohistochemical parameter to exclude malignant
      mesothelioma.

PMID- 8293415
TI  - Metastatic carcinoma of uncertain primary site: a retrospective review of 57
      patients treated with vincristine, doxorubicin, cyclophosphamide (VAC) or VAC
      alternating with cisplatin and etoposide (VAC/PE).
AB  - BACKGROUND: Metastatic carcinoma of uncertain primary site (CUPS) is a common
      problem and has a poor prognosis. The intention of this study was to determine
      whether the addition of cisplatin and etoposide (PE) to vincristine, doxorubicin
      and cyclophosphamide (VAC) chemotherapy improves outcome. METHODS: Fifty-seven
      consecutive patients with an initial diagnosis of CUPS were studied. The first 40
      patients had received six or 10 cycles of VAC and 17 patients VAC alternating
      with PE for six cycles. Review of histology using immunohistochemical techniques
      where appropriate was performed in all cases. RESULTS: Histologic review resulted
      in six tumors reclassified as non-Hodgkin's lymphoma (NHL), one as
      hepatocarcinoma, and one as adenocarcinoma. Six of the 11 responses occurred in
      patients with a review diagnosis of NHL. If the six cases of NHL and the case of
      hepatocarcinoma were excluded, there was no difference in survival between VAC
      and VAC/PE treated patients. Five patients with true CUPS who responded to VAC or
      VAC/PE had poorly differentiated histology, and this group (n = 24) also had a
      significantly longer survival. CONCLUSIONS: Some patients thought to have CUPS
      actually have NHL, and it is this group which responds well to chemotherapy. True
      CUPS patients respond to chemotherapy only if the tumor is poorly differentiated;
      survival is significantly longer for this group of patients. An advantage for
      VAC/PE over VAC chemotherapy was not identified.

PMID- 8293416
TI  - Paratesticular rhabdomyosarcoma: delayed effects of multimodality therapy and
      implications for current management.
AB  - BACKGROUND: The combined modalities of surgery, chemotherapy, and radiation
      therapy have greatly improved the survival rate in childhood paratesticular
      rhabdomyosarcoma, but the incidence of complications and late side effects is a
      cause for concern. METHODS: We reviewed the records of 18 patients treated for
      paratesticular rhabdomyosarcoma at St. Jude Children's Research Hospital between
      1962 and 1989. Patients with Group I disease were treated with orchiectomy,
      retroperitoneal lymph node dissection, and multi-agent chemotherapy; more
      advanced cases also received radiation therapy with concurrent chemotherapy.
      RESULTS: Sequelae included esophageal and common bile duct stricture, inguinal
      nerve entrapment syndrome, and small bowel obstruction. Short stature was found
      in all children whose spines were irradiated via para-aortic fields (34-37 Gy)
      prior to puberty. Two of 18 patients died from treatment complications and one
      from progressive disease. CONCLUSIONS: Multimodality treatment offers an
      excellent prognosis in paratesticular rhabdomyosarcoma, but is associated with
      significant morbidity and mortality rates. A discussion of therapy components and
      their application to disease stages suggests possible approaches to optimizing
      treatment for this therapy-sensitive malignancy.

PMID- 8293417
TI  - Treatment of primary or relapsing limb cancer by isolation perfusion with high
      dose alpha-tumor necrosis factor, gamma-interferon, and melphalan.
AB  - BACKGROUND: Utilization of alpha-tumor necrosis factor (alpha-TNF) in clinical
      practice is limited by severe general side effects. Very promising results with
      low toxicity were reported with administration of alpha-TNF by isolation
      perfusion in extracorporeal circulation. METHODS: From December 1991 to November
      1992, 14 patients underwent perfusion with alpha-TNF (2-4 mg, total dose), gamma
      interferon (1.5 x 10(6) IU), and melphalan (10 mg/l/perfused limb). Twelve
      patients presented in-transit metastases of the limbs, one patient, a clear cell
      sarcoma of the hand, and one patient, a wide spindle cell carcinoma of the thigh.
      Perfusion lasted 90 minutes and was conducted in mild hyperthermia (38-40.5
      degrees C, muscle temperature). RESULTS: Nine complete regressions and four
      stable diseases were recorded. In one case, a reliable evaluation of response was
      not possible for diffused tissue necrosis. Five patients relapsed or progressed
      locally from 3 to 4 months after surgery, five presented distant localizations
      from 2 to 7 months after surgery, and one died of disease 6 months after
      perfusion. Twelve patients are alive, seven without evidence of disease. A septic
      like shock syndrome was observed in all patients and required administration of
      dopamine, dobutamine, or noradrenaline. One patient died 30 days after perfusion
      from a multiorgan-failure syndrome, likely due to alpha-TNF. The follow-up time
      ranges from 4 to 15 months (median, 6). CONCLUSIONS: The preliminary, impressive
      results reported in other series were not completely confirmed in this study
      adopting the same treatment scheme. Further clinical experience and biologic data
      are needed to state the real efficacy of the approach and to reduce the severe
      general toxicity consistently associated with this type of treatment.

PMID- 8293418
TI  - Therapy of venous thromboembolism in patients with brain metastases.
AB  - BACKGROUND: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are common
      in patients with brain metastases. Few data exist to help guide the clinician's
      choice between the two therapeutic options of anticoagulation and inferior vena
      cava filter placement. METHODS: The authors reviewed their institutions'
      experience with the treatment of venous thromboembolism in 51 adult patients with
      known brain metastases since 1980. RESULTS: Ten patients were initially treated
      with Greenfield filters; four (40%) had recurrent nonfatal thromboembolic events
      (two PE and two DVT), and three required anticoagulation. Thirty-nine patients
      were treated initially with anticoagulation; none of these patients later
      received filters. Two patients with DVT were untreated and both died of PE. Among
      42 patients who received anticoagulation, the duration of anticoagulation ranged
      from 5 to 563 days (mean, 100 days). Two patients who received anticoagulation
      experienced devastating central nervous system hemorrhage in the setting of
      supratherapeutic anticoagulation by conventional laboratory criteria. A third
      patient experienced a minor deterioration, possibly attributable to hemorrhage,
      for a 7% (3 of 42) incidence of serious central nervous system complications.
      Three asymptomatic patients developed hyperdensity within metastases on routine
      follow-up noncontrast computed tomography scan, suggesting possible intratumoral
      hemorrhage. Three patients taking warfarin had recurrent DVT with prothrombin
      time between 15.1 and 17.7. Systemic bleeding complications were generally minor
      and occurred in only eight patients (19%). CONCLUSIONS: Anticoagulation is more
      effective than Greenfield filters and acceptably safe when maintained in the
      therapeutic range in most patients with brain metastases and venous
      thromboembolism.

PMID- 8293419
TI  - The National Cancer Data Base. A mechanism for assessment of patient care.
AB  - BACKGROUND: A mechanism for cancer patient care assessment was created. Data
      evaluations will enable clinicians and hospital staffs to appraise trends and
      compare their results with state, regional, and national figures. METHODS: Data
      are collected annually on all forms of cancer from all parts of the country,
      including patient characteristics, tumor characteristics, first-course treatment,
      and follow-up. RESULTS: Data for one or more years were received from a total of
      1071 hospitals. This large, convenience sample of United States cancers included
      approximately 220,000 cases from 1985, 272,000 cases from 1988, and 409,000 cases
      from 1990. The seven most commonly reported cancers were breast, lung, prostate,
      colon, cervix, bladder, and rectum. In a 1993 National Cancer Data Base (NCDB)
      Annual Review, several disease categories and special subjects were analyzed,
      including colorectal, breast, and prostate cancer, melanoma, cancer in children
      and adolescents, cancer in hispanics, time trends in TNM staging, as well as NCDB
      data quality and hospital participation. CONCLUSIONS: A multipurpose partnership
      between the NCDB and the Cancer Liaison Physician Network of the Commission on
      Cancer will be formed at the state and local level to promote NCDB participation
      as well as to disseminate the NCDB clinical findings. Additional sites will be
      covered in Annual Reviews, and highlights of those reports will be provided to
      Liaison Physicians of the Commission who are actively involved in the care of
      cancer patients to inform them of the latest findings.

PMID- 8293420
TI  - Antibody-induced apoptosis in a human leukemia cell line is energy dependent:
      thermochemical analysis of cellular metabolism.
AB  - The mouse monoclonal anti-BAL antibody induced apoptosis in a pre-B acute
      lymphocytic leukemia cell line within 2 days of incubation, after being
      crosslinked by a secondary antibody. The antibody specifically recognized a 37
      kDa membrane protein that was expressed on a wide spectrum of normal and
      malignant cells, but induced programmed cell death in only very few of these
      cells. In this study, we have followed the initial kinetics of the antibody
      induced cell death in the human acute lymphocytic leukemia cell line KM-3, by
      microcalorimetric measurements in conjunction with determination of the cellular
      proliferation rate and DNA fragmentation. An increase in metabolic activity was
      observed already after incubating the cells for 20 min with crosslinked anti-BAL
      antibody, which was several hours before significant growth inhibition and DNA
      fragmentation were detected. These data show for the first time that the
      initiation phase of antibody-induced apoptosis is an active, energy-dependent
      process and not merely an effect of receptor blocking.

PMID- 8293421
TI  - Glutathione and glutathione linked enzymes in human small cell lung cancer cell
      lines.
AB  - Glutathione levels and several glutathione-linked enzyme activities have been
      variably correlated with cisplatin chemosensitivity in cultured neoplastic cells.
      In order to determine the relative contribution of the glutathione-linked enzymes
      towards mediating inherent cisplatin resistance in cancer cells, we have measured
      the chemosensitivity to cisplatin, glutathione levels and activities of
      glutathione S-transferase, glutathione peroxidase, glutathione reductase and
      glucose-6-phosphate dehydrogenase in 8 cultured human small cell lung cancer
      (SCLC) cell lines with widely differing cisplatin sensitivities. Of these
      parameters, only glutathione S-transferase activity correlated with degree of
      cisplatin resistance in a linear fashion.

PMID- 8293422
TI  - Metallothionein in human lung carcinoma.
AB  - Eleven pairs of surgically resected lung cancers and corresponding non-neoplastic
      lung tissue were evaluated for metallothionein (MT) and metal content (cadmium
      and copper) by the heme/109Cd binding assay and atomic absorption spectroscopy,
      respectively. Tissue samples, obtained from patients ranging in age from 51 to
      79, included six adenocarcinomas, two small cell carcinomas, one mixed cell
      carcinoma, one squamous cell carcinoma, and one carcinoma of non-primary origin
      (i.e., melanoma). Paired t-tests showed that metallothionein and copper
      concentrations in lung tumor tissue were significantly elevated when compared to
      non-malignant lung tissue. Cu was the major metal associated with the 10 kDa MT
      fraction in lung tumors whereas Cd was the primary metal bound to MT from non
      neoplastic lung tissue. Since Cu-thionein is also known to be elevated in fetal
      lung tissue, the possibility exists that MT might represent an oncodevelopmental
      product which is useful as a biomarker for the early detection of lung carcinoma.

PMID- 8293423
TI  - Comparative analysis of the methylation status of the 5' flanking region of Ha
      ras in B6C3F1, C3H/He and C57BL/6 mouse liver.
AB  - We examined the methylation status of the 5' flanking region of Ha-ras in the
      liver of the liver tumor-prone B6C3F1 male (C57BL/6 female x C3H/He male) and
      C3H/He male, plus the relatively resistant C57BL/6 male mouse strains. Southern
      analysis revealed the presence of CCGG sites methylated at the internal cytosine,
      as well as unmethylated CCGG sites in all three strains. Digestion with StyI and
      XhoI revealed an unmethylated XhoI site in the C57BL/6 male. This pattern is not
      obvious in the B6C3F1 or C3H/He, indicating sequence variation and/or less
      methylation of Ha-ras in those strains of mice that exhibit a high propensity
      towards development of liver tumors.

PMID- 8293424
TI  - Effects of fatty acids on invasion through reconstituted basement membrane
      ('Matrigel') by a human breast cancer cell line.
AB  - An in vitro invasion assay system was used to examine the effects of linoleic
      acid, an omega-6 fatty acid, and two omega-3 fatty acids, eicosapentaenoic acid
      and docosahexaenoic acid, on the invasive capacity of MDA-MB-435 human breast
      cancer cells. Linoleic acid stimulated, and the omega-3 fatty acids inhibited,
      tumor cell invasion at concentrations of 0.25 and 0.5 microgram/ml. Indomethacin,
      20 micrograms/ml, completely suppressed the stimulatory activity of linoleic
      acid, suggesting that these fatty acid effects are mediated via eicosanoid
      biosynthesis.

PMID- 8293425
TI  - Vasopressin and oxytocin production by non-neuroendocrine lung carcinomas: an
      apparent low incidence of gene expression.
AB  - In previous studies we have demonstrated the high incidence of vasopressin gene
      expression as a characteristic feature of small-cell carcinoma of the lung. In
      the present study we examined expression of this gene in non-neuroendocrine
      tumors to determine if vasopressin production is a common feature of all lung
      tumors. We carried out the immunohistochemical evaluation of 22 non
      neuroendocrine tumors (12 adenocarcinomas and 10 squamous-cell carcinomas) with
      antibodies to vasopressin, to oxytocin, and to their related neurophysins. The
      antibody preparations directed against vasopressin, oxytocin, or oxytocin
      associated human neurophysin did not react with any of the tumors examined. Of
      two monoclonal antibodies to vasopressin-associated human neurophysin used, one
      did not react with any of the tumors, while the other stained neoplastic cells in
      only one adenocarcinoma and one squamous-cell carcinoma. These findings, taken
      with previous reports, indicate that among lung carcinomas, a high incidence of
      vasopressin/oxytocin gene expression is confined to neuroendocrine tumors.

PMID- 8293426
TI  - Inhibition of rat mammary carcinogenesis by inositol hexaphosphate (phytic acid).
      A pilot study.
AB  - Since phytic acid (inositol hexaphosphate, InsP6) and inositol (Ins) have been
      demonstrated to have anti-tumor and anti-cell proliferative action in several
      experimental models of carcinogenesis, in a pilot study we have examined their
      effect on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumor model.
      Starting a week prior to induction with DMBA, the drinking water of female
      Sprague-Dawley rats was supplemented with either: 15 mM InsP6, 15 mM Ins, or 15
      mM InsP6 + 15 mM Ins; a control group received no inositol compounds. Animals (55
      day-old) were given a single dose of DMBA (20 mg) in 1 ml of sesame oil by oral
      intubation. Four additional groups not receiving DMBA, but drinking tap water,
      InsP6, Ins, or InsP6 + Ins of the same molarity as experimental groups were
      observed for the duration of the study to monitor for any putative toxicity
      following this long-term treatment. As opposed to the DMBA-only group, rats
      treated with InsP6 +/- Ins showed a 48% reduction in the number of tumors/tumor
      bearing animal (tumor multiplicity) and a 40% reduction in the number of
      tumors/rat. In contrast to 20% rats in DMBA-only group, only 0-8% animals in the
      treatment group had 5 or more tumors. Likewise, the tumor incidence was reduced
      by 19% in InsP6 +/- Ins as compared to control untreated animals. The tumors in
      the treated groups were also 16% smaller in size. Data from this pilot study
      suggest that in addition to being effective against colon cancer, InsP6 +/- Ins
      may be protective against mammary carcinoma as well; additional studies are
      however warranted.

PMID- 8293427
TI  - Potential of retinoids in cancer prevention.

PMID- 8293428
TI  - Radionuclide therapy in oncology.

PMID- 8293429
TI  - Topoisomerase I inhibitors: topotecan and irenotecan.

PMID- 8293430
TI  - Induced autologous graft-versus-host disease for the treatment of cancer.

PMID- 8293431
TI  - [Registry of research projects. II. The health care program of the Czech
      Republic. III. Projects begun in 1993].

PMID- 8293432
TI  - [Dialysis therapy in the Czech Republic in 1991].
AB  - In the Czech Republic in 1991 2064 patients with chronic renal failure were
      treated in 43 haemodialysation centres. The number of newly enlisted patients was
      high--655 patients. Despite this the mean number of 196.5 patients/1 million
      population is lower than the European average. Fear of doctors is aroused by
      inadequate technical equipment and the lagging replacement of amortized
      equipment. The age of dialyzed patients is rising, the number of polymorbid
      patients and diabetics is increasing. It can be assumed that the mortality will
      increase and the number of transplantable patients will decline. A high incidence
      of hepatitis still persists. The most frequent cause of acute renal failure are
      complications after surgery. Acute haemodialysis on account of intoxication was
      made most frequently after intoxications with drugs.

PMID- 8293433
TI  - [Prediction of needs in dialysis therapy].
AB  - Planning of future needs of Renal Replacement Therapy (RRT) Programme is
      frequently based on comparison of national data with data from other countries.
      Often, the dynamics of RRT development is disregarded and dialysis and
      transplantation assessed as separate entities, too. Such approach may lead to
      underestimation of present level of RRT availability and overestimation of
      immediate future needs. Transplantation activity and number of patients requiring
      dialysis are interrelated variables. Under steady state, their relation may be
      described as N = TX + U where N denotes incidence of chronic renal failure, TX
      transplantation activity, and U stands for mortality rate of dialysed population.
      Considering mortality rate equal to 10% of dialysed population (P), an equation
      describing the interrelation of transplantation activity and number of patients
      requiring dialysis may be devised: P = (N - TX)/0.1. This equation can be used to
      calculate target values of RRT programme. The time course of RRT needs to reach
      the target figures may be predicted from a simple differential equation dP/dT = N
      - 0.1. P - TX, taking into account dynamic character of this process.

PMID- 8293434
TI  - [Acute effects of hemodialysis on circulating parathormone, osteocalcin and
      alkaline phosphatase in patients with chronic renal failure].
AB  - The authors investigated biochemical indicators of the phosphocalcium metabolism
      in 18 patients dialyzed for prolonged periods on account of chronic renal failure
      before and after 5-hour dialysis. During dialysis serum creatinine and phosphorus
      levels declined and serum calcium levels rose. The level of immunoreactive
      parathyroid hormone (C-terminal), total alkaline phosphatase and gamma-glutamyl
      transferase did not change. During five hours of dialysis, as compared with
      alkaline phosphatase, mainly its bone isoenzyme, a marked increase of
      osteocalcin, an index of de novo bone formation, was recorded. From the
      investigation it is obvious that osteocalcin with a half-life of 5 minutes is an
      index of acute changes of the bone metabolism and its rise during dialysis
      indicates the favourable effect of dialysis on osteoblast activity.

PMID- 8293435
TI  - [Increased lymphocyte reactivity in patients with chronic kidney failure].
AB  - Lymphocytes isolated from peripheral blood of patients with irreversible renal
      failure and cultivated in non-stimulated cell cultures incorporated significantly
      more 3H-thymidine and released more beta-2-microglobulin than lymphocytes of the
      patients' healthy relatives (possible kidney donors) and than lymphocytes of non
      related blood donors.

PMID- 8293436
TI  - [Consupren in prophylactic therapy after kidney transplantation].
AB  - Thirty patients after a first transplantation of the kidney from a dead donor
      were treated with Consupren Galena combined with azathioprine and prednisone for
      a period of at least one year. As control served a comparable historical group of
      50 patients treated with a combination of three immunosuppressive drugs using
      Sandimmune, Sandoz. No significant differences were found between the two groups
      as regards the functional development of the grafts, the number of lost grafts,
      the cumulative survival of grafts, the number of rejections and the number of
      deaths. As to undesirable effects there were insignificantly more patients with a
      nephrotoxic episode in group CS where also repeated nephrotoxic episodes were
      recorded. The most frequent undesirable effect in group CS was hirsutism in half
      the patients. Consupren used in prophylactic treatment in combination with a
      azathioprine and prednisone appears to be a comparable immunosuppressive regime
      as that which comprises Sandimmune, Sandoz.

PMID- 8293437
TI  - [The Churg-Strauss syndrome with rapidly progressive glomerulonephritis positive
      for antineutrophil cytoplasmic antibodies].
AB  - Renal failure developed in a patient treated for worsening spastic dyspnoea, high
      erythrocyte sedimentation rate and enlarged peribronchial lymph nodes by the
      antituberculotic regimen. Renal biopsy disclosed rapidly progressive
      glomerulonephritis with 95% crescents, granulomatous periglomerulonephritis
      vasculitis and eosinophilic interstitial infiltrates. On the basis of the
      positivity of antineutrophil cytoplasmic antibodies (ANCA), eosinophilia and
      profound ventilatory impairment the diagnosis of Churg-Strauss syndrome was
      established. The patient was treated by plasma exchanges and combined
      immunosuppression with the profound effect on erythrocyte sedimentation rate,
      eosinophilia a negativization of ANCA and preservation of at least minimal renal
      function. Further therapy was complicated by steroid diabetes, repeated
      leucopenia and exacerbation of spastic bronchitis and eventually by the massive
      gastrointestinal haemorrhage from asymptomatic gastric ulcer. There were no signs
      of inflammation in renal autopsy specimens with prevailing glomerulosclerosis a
      periglomerular fibrosis. Renal impairment is rare in Churg-Strauss syndrome and
      it is only exceptionally the cause of renal failure.

PMID- 8293438
TI  - [Treatment of patients who refuse blood transfusion].

PMID- 8293439
TI  - [Rhabdomyolysis and acute renal failure].
AB  - Rhabdomyolysis is damage of the skeletal muscles due to different causes which
      leads to the release of the contents of muscle cells into the blood stream and
      conversely to the penetration of water and other substances into muscles via the
      damaged membrane. This initiates many processes which damage the organism:
      hypovolaemia, hypocalcaemia, hyperkalaemia, hyperuricaemia, disseminated
      intravascular coagulation, renal failure. Renal failure in particular is a
      frequent and very serious complication. However, when correct treatment is
      provided, it is usually reversible. The diagnosis and differential diagnosis is
      not difficult if the possible presence of rhabdomyolysis is considered. Therapy
      involves in particular supplementation of the vascular volume and forced
      diuresis.

PMID- 8293440
TI  - [Lisinopril in the monotherapy of patients with essential hypertension: the
      effect of therapy on glucose and lipid metabolism].
AB  - Twenty patients with mild or medium severe essential hypertension were treated
      with lisinopril (Prinivil), 20 or 40 mg resp. by the oral route per day. After
      six weeks of treatment the mean values of systolic pressure declined from 169 +/-
      4.38 mm Hg to 149 +/- 3.96 mm Hg and the diastolic pressure from 108 +/- 0.99 mm
      Hg to 91 +/- 1.77 mm Hg. The differences were statistically significant. In 40%
      of the patients it was necessary to increase the daily dose of lisinopril to 40
      mg. When this was used, the mean values of systolic pressure declined to 140 +/-
      3.18 mm Hg and those of diastolic pressure declined to 85 +/- 1.43 mm Hg during
      the subsequent six weeks. The blood pressure of all investigated patients was
      within the range of reference values. The authors recorded a positive effect on
      the glucose metabolism in particular in patients with impaired glucose tolerance.
      The mean blood sugar levels during the second hour following glucose
      administration during the oGTT declined from 9.81 +/- 0.54 mmol/l before
      treatment to 7.28 +/- 0.79 mmol/l after 12 weeks of lisinopril treatment. The
      values of immunoreactive insulin after the mentioned intervals declined from
      82.49 +/- 5.6 to 34.94 +/- 8.37 microM/ml. The investigated parameters of the
      lipid spectrum did not change after 12 weeks of treatment. The authors did not
      observe any marked side-effects of treatment.

PMID- 8293441
TI  - [Hypoperfusion of the brain in cardiac rhythm disorders].
AB  - In 134 patients (age 41-74 years) with symptoms of a transient ischaemic attack
      the authors made an ultrasonic dopplerometric examination of the main arteries of
      the head and a rheoencephalographic examination using the method of polygraphic
      recording with an ECG tracing II. st. 1. as well as in extreme position of the
      head and neck. In the investigated group in seven subjects a severe disorder of
      the cardiac rhythm was recorded with more than one third of ectopic ventricular
      contractions. The authors elaborated criteria for the objective expression of the
      impact of haemodynamic changes on the cerebral circulation. When doing so, they
      took into account the number of inadequate ventricular contractions with a pulse
      deficit in the periphery, the frequency of inadequate contractions and their
      haemodynamic effect the consequence of which was reduction of the pulse volume
      and slowing down of the blood flow. According to these criteria dysrhythmia was
      the cause of cerebral ischaemia in 4.5% of all subjects included in the authors'
      group. In the group of patients with a severe disorder of the cardiac rhythm
      dysrhythmia was the cause of a transient ischaemic attack in 86% of the patients.
      Trespassing of the ischaemic threshold is promoted also by a poorer blood supply
      in extreme positions of the head and neck which may occur in everyday life or
      during sleep.

PMID- 8293442
TI  - [Short-term changes in cardiovascular mortality rates during a synodic month].
AB  - Statistically high significant periodicity (in the range of 2.3 to 4.2 days) in
      the cardiovascular mortality has been proved. This is connected with the
      alternation of lunar phases in the course of the synodic moon. The explanation as
      some endogene rhythms was excluded. To determine the origin of these short
      periodical changes will be a subject of further investigations.

PMID- 8293443
TI  - [Acute kidney failure associated with rhabdomyolysis].
AB  - The authors describe three cases of rhabdomyolysis and acute renal failure. In
      all patients rhabdomyolysis developed in conjunction with ingestion of alcohol,
      in two moreover in combination with compression of an extremity by body weight
      during prolonged immobility. One patient was hospitalized on the day when
      rhabdomyolysis developed, the second one more than 24 hours after and the third
      one only several days after development of the condition. In none of them the
      diagnosis was established before the development of renal failure. All were
      subjected repeatedly to haemodialysis. One patient died from a complication-
      embolism of the brain--the remaining two patients recovered without sequelae. In
      the discussion the authors deal with reasons of late diagnosis of the disease.

PMID- 8293444
TI  - [Admission requirements to the Charles University Medical School in Prague for
      1992-1993].

PMID- 8293445
TI  - Phenol sulfotransferase expression in the airways: enzymological and
      immunohistochemical demonstration.
AB  - Phenol (aryl) sulfotransferases (PSTs) provide a conjugative pathway that
      detoxifies hydroxylated aromatic xenobiotics by esterification with sulfate. Both
      human and bovine airways have been reported to use this pathway, and in this
      investigation the bovine system is examined. PST activity in tracheal through
      fourth generation bronchial mucosal cytosols was 0.1-0.35 nmol/mg protein/min.
      Activity was generally greater in more distal bronchi and in parenchymal
      extracts, which contained 0.6-3 nmol/mg/min PST activity. Comparison of the PST
      activities of bronchial and parenchymal cytosols indicated similar pH activity
      profiles, although steady state kinetic measurements revealed different Km values
      for the acceptor substrate 2-naphthol (13.7 microM for bronchial, 31.3 microM for
      parenchymal). Anion exchange chromatography indicated two PST isoforms being
      expressed in different ratios. Immunoblot analysis with mouse anti-bovine PST
      revealed a closely spaced doublet at 32 kDa in both bronchial mucosal and
      parenchymal cytosolic extracts; however, this doublet was unequally stained in
      parenchymal extracts. Immunohistochemical analyses revealed faint positive
      staining of the tracheobronchial epithelium. Greatest immunostaining was observed
      in the nonciliated secretory epithelial cells of the bronchioles, whereas
      surrounding smooth muscle, endothelial cells, and alveoli were immunonegative.
      These results are consistent with the known locations of other detoxification
      enzymes within the airways.

PMID- 8293446
TI  - Cellular distribution of parvalbumin immunoreactivity in the peripheral
      vestibular system of three rodents.
AB  - The cellular distribution of parvalbumin immunoreactivity in the vestibular
      peripheral system of mouse, rat, and guinea pig was investigated by light and
      electron microscopy. Parvalbumin was found in all neurons of the vestibular
      ganglia of these species but in the sensory epithelia immunoreactivity was
      restricted to type I hair cells localized exclusively in the central areas. The
      very intense staining pattern was similar in the cristae ampullares and utricles
      of all three species but a faint immunoreaction was also detectable in sensory
      cells of peripheral areas of rat cristae. The parvalbumin-immunoreactive type I
      sensory cells are connected by nerve fibres of the calyx unit type which are
      known selectively to contain calretinin.

PMID- 8293447
TI  - Distribution of glycosylphosphatidylinositol-specific phospholipase D mRNA in
      bovine tissue sections.
AB  - It has been reported that mammalian serum, and to a lower extent mammalian liver,
      brain, pancreas, udder, and milk, contain glycosylphosphatidylinositol-specific
      phospholipase D activity. However, the sites of synthesis have not been
      determined. In order to study in which cell(s) of the organism synthesis of
      glycosylphosphatidylinositol-specific phospholipase D takes place, we undertook a
      systematic screening of 12 different bovine tissues. In situ hybridization
      experiments with a specific anti-sense RNA probe, derived from a bovine liver
      cDNA, revealed that glycosylphosphatidylinositol-specific phospholipase D mRNA is
      present in mast cells of the adrenal gland, lung, and liver. On the other hand,
      our specific probe detected no mRNA in bovine pancreas, brain, and udder,
      although enzyme activity has been reported in these tissues. Northern blot
      analysis of total bovine liver RNA demonstrated two distinct
      glycosylphosphatidylinositol-specific phospholipase D mRNAs of approximately 3.3
      kb and 4 kb length suggesting that two forms of the enzyme may exist.

PMID- 8293448
TI  - In vivo secretory responses of submandibular glands in streptozotocin-diabetic
      rats to sympathetic and parasympathetic nerve stimulation.
AB  - Submandibular gland responses to sympathetic and parasympathetic nerve
      stimulation were studied in streptozotocin-diabetic rats. Morphologically, the
      acinar cells in control glands were relatively uniform in size and contained
      electron-lucent granules. The granular ducts were distinguished by the presence
      of electron-dense granules. With the exception of intracellular lipid droplets
      and the presence of a few autophagosomes in diabetic glands, no consistent
      differences in acinar cell structure were observed. In contrast, the diameter of
      the granular ducts and the granule content of their cells were less in diabetic
      glands. At 3 weeks sympathetic flow rate, salivary protein concentration, and
      total protein output were unaffected by diabetes. Sympathetic flow rate was
      greater at 3 months, and the concentration of protein in the saliva was lower. In
      6-month diabetic rats flow rate remained increased, but protein concentration and
      total protein output were reduced. The decrease in salivary protein concentration
      at 3 and 6 months was accompanied by a reduction in secretory granule release
      from acinar and granular duct cells. No consistent differences in flow rate,
      protein concentration, protein output, or secretory granule release were observed
      following parasympathetic stimulation. We conclude that the effects of diabetes
      on nerve-stimulated flow rate and protein release depend on the duration of
      diabetes and the type of stimulation, and are independent of one another.

PMID- 8293449
TI  - Immunocytochemical effects of thyroxine stimulation on the adenohypophysis of
      dwarf (dw) mutant mice.
AB  - The effects of dietary thyroxine on the immunoreactivity of cells in the pars
      distalis of the adenohypophysis in dwarf (dw/dw) mice were determined by
      ultrastructural immunocytochemistry. In nontreated dwarfs only
      adrenocorticotropic hormone (ACTH) cells and luteinizing hormone (LH) cells
      showed positive reactions to their respective antibodies, whereas no cells showed
      immunoreactivity to antibodies to growth hormone (GH), thyroid-stimulating
      hormone (TSH), or prolactin (Prl). In dwarfs supplemented postnatally with
      dietary thyroxine for 9 wks, the treatment failed to produce immunoreactive GH,
      TSH or Prl cells. However, LH cells became more prominent and fully developed,
      with denser concentrations of immunoreactive particles overlying the secretory
      granules than occurred in nontreated dwarfs. In thyroxine-treated dwarfs, ACTH
      cells were similar in ultrastructural features and immunoreactivity to those in
      nontreated dwarfs.

PMID- 8293450
TI  - Effects of background adaptation on alpha-MSH and beta-endorphin in secretory
      granule types of melanotrope cells of Xenopus laevis.
AB  - Placing the clawed toad Xenopus laevis on a black background stimulates the
      melanotrope cells in the pars intermedia of the pituitary gland to release
      proopiomelanocortin (POMC)-derived peptides, including alpha-MSH and N-acetyl
      beta-endorphin. In this study three types of secretory granules, electron-dense
      (approximately 130 nm phi), moderately electron-dense (approximately 160 nm phi)
      and electron-lucent (approximately 180 nm phi), have been identified in these
      cells. Apparently, only dark granules are formed by the Golgi apparatus and
      lucent granules release their contents via exocytosis. Immuno-electron microscopy
      (immunogold double labelling) of glutaraldehyde-fixed and freeze-substituted
      material shows that desacetyl-alpha-MSH and N-acetyl-beta-endorphin coexist in
      all three granule types. Quantification of immunostaining revealed that
      immunoreactivities to these peptides are lowest in the dark granules and highest
      in the light ones. It is proposed that intragranular processing of POMC to
      immunoreactive desacetyl-alpha-MSH and N-acetyl-beta-endorphin involves an
      increase in granule size and a decrease in granule electron density. Black
      background-induced activation of the melanotrope cell is reflected by an increase
      in immunoreactivity of the secretory granules to each of the antisera. This
      suggests that cell activation stimulates the formation of peptides by
      intragranular processing of POMC and/or of intermediate POMC-processing products.
      In addition, cell activation evoked an increase in the percentage of the granule
      population that reacts with anti-N-acetyl-beta-endorphin, probably by stimulating
      intragranular acetylation of beta-endorphin. Apparently, this acetylation is a
      regulated event that occurs in the cytoplasm, independently from the acetylation
      of desacetyl-alpha-MSH which takes place near the plasmalemma at the time of
      granule exocytosis.

PMID- 8293451
TI  - Scanning and transmission electron-microscopic study of peripolar cells in the
      newborn lamb kidney.
AB  - Scanning and transmission electron microscopy were used to study the
      ultrastructural characteristics and positions of granulated peripolar cells in
      newborn lamb kidney. Following tissue fixation by vascular perfusion in situ, the
      vascular pole region of the glomerulus was exposed for examination by scanning
      electron microscopy following removal of the glomerular tuft. Peripolar cells
      were recognized by their surface morphology enabling their quantification and an
      assessment of the relationship of their position in the renal cortex. The
      prominent expression of peripolar cells in this species was confirmed. Almost
      every vascular pole examined revealed peripolar cells (405 out of 407; 99.5%) and
      thus, throughout the cortex, the distribution of peripolar cells was the same as
      the distribution of renal corpuscles. Larger, more protruding peripolar cells
      were observed in the outer cortical renal corpuscles. The numbers of peripolar
      cells encircling each vascular pole ranged from 1 to 10. There was no correlation
      between number of granulated peripolar cells at the vascular pole and the
      position of the renal corpuscle within the renal cortex. As viewed by
      transmission electron microscopy, organelles of protein synthesis were abundant
      in the cytoplasm of peripolar cells. Exocytosis of cytoplasmic granules was
      observed by both scanning and transmission electron microscopy implying that a
      process of regulative secretion occurs from these cells. The use of
      ultrastructural techniques has provided evidence supporting the concept that
      peripolar cells are prominent in the cuff region of each renal corpuscle of the
      newborn lamb and furthermore that peripolar cells in this species most likely
      have a secretory function.

PMID- 8293452
TI  - Immunocytochemical mapping of the novel echinoderm neuropeptide SALMFamide 1 (S1)
      in the starfish Asterias rubens.
AB  - The recent isolation and characterization of the SALMFamide neuropeptides S1 and
      S2 from the starfish Asterias rubens has initiated a series of studies on their
      distribution. Specific antisera have been raised against S1 and used in light
      microscopical immunocytochemistry. The results of this study reveal for the first
      time a possible hyponeural innervation of the visceral musculature of the gut and
      the widespread neuronal distribution of S1, (i) in axons and cell bodies of both
      ectoneural and hyponeural regions of the radial nerve cord and circumoral nerve
      ring, (ii) in the nerve ring and nerve plexus of the tube feet, (iii) in the
      apical muscle, (iv) in skin, and (v) extensively throughout the digestive system.
      These discoveries are of particular interest in terms of the possible functional
      roles for S1 in Asterias rubens.

PMID- 8293453
TI  - Comparison of the intracellular pathways of immunoglobulin-G and low density
      lipoprotein in cultured human term trophoblast cells.
AB  - Trophoblast cells were cultured on microporous membrane filters. After incubation
      at different times with gold-conjugated ligands, the cells were processed for
      electron microscopy. Gold particles indicating the presence of both IgG and LDL
      appeared in a time-dependent manner in coated pits and coated vesicles. LDL-gold
      appeared primarily within lysosomes whereas approximately 50% of the internalized
      IgG-gold appeared within vesicles (diameters ranging from 35 to 80 nm) near the
      basal regions of the cell. These vesicles may be the protective mechanism which
      prevents IgG breakdown during transcytosis across trophoblast cells, thus
      allowing transport of the intact molecule to the fetus.

PMID- 8293454
TI  - Immunocytochemical identification of growth hormone (GH) cells in the pituitary
      of three anuran species using an antiserum against purified bullfrog GH.
AB  - An antiserum was prepared against the recently purified bullfrog (bf) growth
      hormone (GH); it was applied to sections of brain and pituitary of three urodele
      (Ambystoma, Pleurodeles and Cynops) and three anuran (Xenopus, Bufo vulgaris and
      B. japonicus) species. No immunostaining was obtained in the urodele pituitary,
      being consistent with the results of immunoblot analysis of the pituitary
      homogenate. In the three anuran species, strong immunoreactivity was observed in
      GH cells that were concentrated in the posterodorsal region of the pars distalis.
      No GH-like immunoreactivity was detectable in the brain of any of the species. A
      comparison using adjacent sections stained with anti-bf prolactin (PRL) confirmed
      the anteroventral localization of PRL cells. Colocalization of GH and PRL was not
      apparent. These data suggest that the molecular structure of amphibian GHs is
      considerably different between anurans and urodeles. The antiserum used in the
      present work shows a high species specificity, recognizing only anuran GHs. In
      contrast anti-bfPRL labeled PRL cells in all the amphibian species studied in the
      present work, suggesting that PRLs possess common amino acid sequences recognized
      by the anti-bfPRL.

PMID- 8293455
TI  - Hedgehog, the floor plate, and the zone of polarizing activity.

PMID- 8293456
TI  - The flip side of DNA methylation.

PMID- 8293457
TI  - The structure of transducin G alpha t: more to view than just ras.

PMID- 8293458
TI  - Close similarity between receptor-linked tyrosine phosphatase and rat brain
      proteoglycan.

PMID- 8293459
TI  - Developmental switches in the immune system.

PMID- 8293460
TI  - Positive selection of lymphocytes.

PMID- 8293461
TI  - Negative selection of lymphocytes.
AB  - Almost by definition, negative selection of T and B lymphocytes cannot be
      absolute. Given that both sets of receptors are derived by stochastic processes,
      recognition of epitopes by lymphocyte receptors will not be an all or none affair
      but a relative one. Too effective a mechanism of negative selection would have
      resulted in deletion of the whole repertoire, as all specificities would have
      cross-reacted with some self-epitope at least to some degree. This review has
      documented some of the influences impacting on emerging T and B cell repertoires
      that result in a removal of the most dangerous self-reactive cells and the
      progressive quantitative and qualitative increase, through positive clonal
      selection, of other cells specific for the actual foreign antigens encountered by
      each individual. T and B lymphocytes pass through a stage where their natural
      reaction to antigen is one of negative selection and on to a later stage where
      the cell is more likely to become activated. Geography plays a role in this; the
      primary lymphoid organs are designed largely to exclude foreign antigens and to
      present self-antigens, whereas the secondary lymphoid organs are designed to
      filter out and concentrate foreign material and to promote costimulatory
      intercellular immune interactions. Ontogeny of individual cells also plays its
      role, probably through the progressive assembly of the full receptor signaling
      machinery, incomplete arrays promoting a negative rather than a positive signal.
      However, the differing susceptibilities of immature and mature cells to silencing
      by deletion or anergy are relative rather than absolute. Negative signaling may
      involve immediate or somewhat delayed death of the anti-self-cell, and in some
      cases the bad cell may have the chance of editing its receptor to create one
      lacking anti-self-reactivity. Alternatively, the cell may receive a nonlethal
      down-regulatory signal and may be induced into a state of anergy. Such anergic
      cells may have a reduced life span, showing that anergy and deletion may shade
      into each other. Upon the removal of antigen (an unlikely event for cells anergic
      to an authentic self-antigen), the state of anergy is reversible. The strength of
      the receptor cross-linking signal may chiefly determine whether deletion (strong
      cross-linking) or anergy (weaker cross-linking) supervenes. Some lymphocytes with
      self-reactivity ignore the self-antigen in question because of low affinity, poor
      accessibility, lack of suitable presentation, or absence of appropriate
      help.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8293462
TI  - Cytokine signal transduction.

PMID- 8293463
TI  - Signal transduction by lymphocyte antigen receptors.
AB  - Despite the differences in the antigens that they recognize and in the effector
      functions they carry out, B and T lymphocytes utilize remarkably similar signal
      transduction components to initiate responses. They both use oligomeric receptors
      that contain distinct recognition and signal transduction subunits. Antigen
      receptors on both cells interact with at least two distinct families of PTKs via
      common sequence motifs, ARAMs, in the cytoplasmic tails of their invariant
      chains, which have likely evolved from a common evolutionary precursor.
      Coreceptors appear to serve to increase the sensitivity of both of these receptor
      systems through events that influence ligand binding and signal transduction. The
      critical role of tyrosine phosphorylation of downstream signaling components,
      such as phospholipase C, is the net result of changes in the balance of the
      action of antigen receptor-regulated PTKs and PTPases. The identification of
      downstream effectors, including calcineurin and Ras, that regulate cellular
      responses, such as lymphokine gene expression, promises the future possibility of
      connecting the complex pathway from the plasma membrane to the nucleus in
      lymphocytes. Insight gained from studies of the signaling pathways downstream of
      TCR and BCR stimulation is likely to contribute significantly to future
      understanding of mechanisms responsible for lymphocyte differentiation and for
      the discrimination of self from nonself in developing and mature cells.

PMID- 8293464
TI  - MHC-dependent antigen processing and peptide presentation: providing ligands for
      T lymphocyte activation.

PMID- 8293465
TI  - T and B memory cells.

PMID- 8293466
TI  - Subversion of the immune system by pathogens.

PMID- 8293467
TI  - A novel macromolecular structure is a target of the promyelocyte-retinoic acid
      receptor oncoprotein.
AB  - Acute promyelocytic leukemia (APL) is associated with a t(15;17) translocation
      that creates the promyelocyte-retinoic acid receptor alpha (PML-RAR alpha) fusion
      gene. Immunohistochemistry demonstrates that PML is a part of a novel
      macromolecular organelle (including at least three other nuclear proteins)
      referred to as PML oncogenic domains (PODs). In APL cells, the POD is disrupted
      into a microparticulate pattern as a consequence of the expression of the PML-RAR
      oncoprotein. RA treatment of APL cells triggers a reorganization of PML to
      generate normal-appearing PODs. We propose that PML-RAR is a dominant negative
      oncoprotein that exerts its putative leukomogenic effect by inhibiting assembly
      of the POD. According to this proposal, not only is the POD a novel structure,
      but it can be ascribed an imputed function such that its disruption leads to
      altered myeloid maturation; this may represent a novel oncogenic target.

PMID- 8293468
TI  - Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute
      promyelocytic leukemia cells.
AB  - Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17)
      translocation that fuses the retinoic acid receptor alpha (RAR alpha) to a novel
      gene product, PML. The involvement of RAR alpha is particularly intriguing in
      view of the efficient therapeutic effect of retinoic acid (RA) in this disease.
      In this report, we show that PML is specifically localized within a discrete
      subnuclear compartment corresponding to nuclear bodies recognized by patient
      autoimmune sera. In APL cells, the PML-RAR alpha hybrid displays an abnormal
      localization and directs RXR and other nuclear antigens into aberrant structures
      that are tightly bound to chromatin. This suggests that the hybrid could exert a
      dominant negative effect by diverting a subset of proteins from their natural
      sites of action. Interestingly, treatment of APL cells with RA induces a complete
      relocalization of each of these proteins. We propose that the beneficial role of
      RA in promoting myeloid differentiation in APL might be related to its ability to
      restore a normal subnuclear organization.

PMID- 8293469
TI  - HhaI methyltransferase flips its target base out of the DNA helix.
AB  - The crystal structure has been determined at 2.8 A resolution for a chemically
      trapped covalent reaction intermediate between the HhaI DNA cytosine-5
      methyltransferase, S-adenosyl-L-homocysteine, and a duplex 13-mer DNA
      oligonucleotide containing methylated 5-fluorocytosine at its target. The DNA is
      located in a cleft between the two domains of the protein and has the
      characteristic conformation of B-form DNA, except for a disrupted G-C base pair
      that contains the target cytosine. The cytosine residue has swung completely out
      of the DNA helix and is positioned in the active site, which itself has undergone
      a large conformational change. The DNA is contacted from both the major and the
      minor grooves, but almost all base-specific interactions between the enzyme and
      the recognition bases occur in the major groove, through two glycine-rich loops
      from the small domain. The structure suggests how the active nucleophile reaches
      its target, directly supports the proposed mechanism for cytosine-5 DNA
      methylation, and illustrates a novel mode of sequence-specific DNA recognition.

PMID- 8293470
TI  - A histone octamer can step around a transcribing polymerase without leaving the
      template.
AB  - The mechanism by which nucleosome cores are displaced and re-formed during
      transcription in vitro has been investigated. A nucleosome core was assembled on
      a short linear DNA template (227 bp) containing an SP6 RNA polymerase promoter
      and a nucleosome-positioning sequence. Transcription induced the translocation of
      the nucleosome core over 75 or 80 bp to two positions at the other end of the
      template, blocking the promoter. At low rNTP concentrations, transfer occurred
      only on the same template molecule, even in the presence of large excesses of
      competitor DNA. On a longer template (262 bp), nucleosome core position after
      transcription depended on its position before transcription. The data suggest
      that the octamer transfers without dissociation from DNA and provide strong
      evidence for a translocation mechanism in which DNA ahead of the polymerase
      uncoils from the octamer as the DNA behind coils around it. In this way, the
      octamer steps around the transcribing polymerase.

PMID- 8293471
TI  - Lipid-anchored influenza hemagglutinin promotes hemifusion, not complete fusion.
AB  - It has been proposed that membrane fusion events such as virus-cell fusion
      proceed through a hemifusion intermediate, a state where lipids but not contents
      of the fusing compartments mix. We engineered the influenza hemagglutinin (HA)
      such that it would be anchored in membranes via a glycosylphosphatidylinositol
      (GPI) tail. GPI-anchored HA forms a trimer that can bind red blood cells (RBCs)
      and change conformation under fusion-inducing conditions. Using RBCs labeled with
      fluorescent lipid or fluorescent soluble content probes, we found that GPI
      anchored HA mediated lipid mixing with similar time course and efficiency as wt
      HA, yet did not mediate transfer of soluble contents. Hence, GPI-anchored HA
      appears to initiate, but not complete, a fusion reaction. We interpret our
      results as evidence for uncoupling a physiological fusion reaction, for trapping
      a hemifusion intermediate, and for assigning a role to a transmembrane domain in
      a fusion event.

PMID- 8293472
TI  - Molecular characterization of a copper transport protein in S. cerevisiae: an
      unexpected role for copper in iron transport.
AB  - We report the identification and characterization of CTR1, a gene in the yeast S.
      cerevisiae that encodes a multispanning plasma membrane protein specifically
      required for high affinity copper transport into the cell. The predicted protein
      contains a methionine- and serine-rich domain that includes 11 examples of the
      sequence Met-X2-Met, a motif noted in proteins involved in bacterial copper
      metabolism. CTR1 mutants and deletion strains have profound deficiency in ferrous
      iron uptake, thus revealing a requirement for copper in mediating ferrous
      transport into the cell. Genetic evidence suggests that the target for this
      requirement is the FET3 gene (detailed in a companion study), predicted to encode
      a copper-containing protein that acts as a cytosolic ferro-oxidase. These
      findings provide an unexpected mechanistic link between the uptake of copper and
      iron.

PMID- 8293473
TI  - The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous
      iron uptake.
AB  - S. cerevisiae accumulate iron by a process requiring a ferrireductase and a
      ferrous transporter. We have isolated a mutant, fet3, defective for high affinity
      Fe(II) uptake. The wild-type FET3 gene was isolated by complementation of the
      mutant defect. Sequence analysis of the gene revealed the presence of an open
      reading frame coding for a protein with strong similarity to the family of blue
      multicopper oxidoreductases. Consistent with the role of copper in iron
      transport, growth of wild-type cells in copper-deficient media resulted in
      decreased ferrous iron transport. Addition of copper, but not other transition
      metals (manganese or zinc), to the assay media resulted in the recovery of Fe(II)
      transporter activity. We suggest that the catalytic activity of the Fet3 protein
      is required for cellular iron accumulation.

PMID- 8293474
TI  - Characterization of SAP-1, a protein recruited by serum response factor to the c
      fos serum response element.

PMID- 8293475
TI  - Coactosin, a 17 kDa F-actin binding protein from Dictyostelium discoideum.
AB  - A 17 kDa protein, designated as coactosin, has been purified from an actin-myosin
      complex reconstituted in vitro from a soluble fraction of Dictyostelium
      discoideum cells. The protein binds to F-actin in vitro without significantly
      altering its viscosity. Immunoblots labeled with monoclonal antibodies indicate
      that part of the protein is associated with the detergent-insoluble cytoskeleton.
      cDNA clones comprising the entire coding region of coactosin have been isolated
      from an expression library. The cDNA-derived amino-acid sequence reveals
      similarities of coactosin to the drebrins identified in neurons and to actin
      binding proteins from other organisms, including yeast ABP1p, and yeast and
      vertebrate cofilins.

PMID- 8293476
TI  - Sarcomeric myosin heavy chain expressed in nonmuscle cells forms thick filaments
      in the presence of substoichiometric amounts of light chains.
AB  - Central to the function of myosin is its ability to assemble into thick filaments
      which interact precisely and specifically with other myofibrillar proteins. We
      have established a novel experimental system for studying myofibrillogenesis
      using transient transfections of COS cells, a monkey kidney cell line. We have
      expressed both full-length rat alpha cardiac myosin heavy chain (MHC) and a
      truncated heavy meromyosin-like alpha MHC (sHMM) and shown that immunoreactive
      MHC proteins of the expected sizes were detected in lysates of transfected cells.
      Surprisingly, the full-length MHC formed large spindle-shaped structures
      throughout the cytoplasm of transfected cells as determined by immunofluorescence
      microscopy. The structures were not found in cells expressing the sHMM construct,
      indicating that their formation required an MHC rod. The spindle-shaped
      structures ranged in length from approximately 1 micron to over 20 microns in
      length and were birefringent suggesting that they are ordered arrays of thick
      filaments. This was confirmed by electron microscopic analysis of the transfected
      cells which revealed arrays of filamentous structures approximately 12 nm in
      diameter at their widest point. In addition, the vast majority of transfected MHC
      did not associate with the endogenous nonmuscle myosin light chains,
      demonstrating that myosin thick filaments can form in the absence of
      stoichiometric amounts of myosin light chains.

PMID- 8293477
TI  - Actin, alpha-actinin, and vinculin are associated with septate junctions in
      Insecta.
AB  - Cytoskeletal elements associated with the smooth septate junctions linking the
      midgut columnar cells of Manduca sexta larvae (Insecta, Lepidoptera) were
      characterized. Myosin subfragment 1 decoration and immunostaining for actin
      demonstrated that the filaments associated with the septate junctions were
      constituted of actin. Moreover, using a combination of immunochemical and
      immunolocalization techniques, evidence is presented that alpha-actinin, myosin
      II, and vinculin are localized close to the specialized plasma membranes. The
      insertion of microfilament bundles into submembranous F-actin/alpha
      actinin/vinculin complexes, previously described in vertebrate junctions of
      adherens type, appears to be a more general organization, including the insect
      septate junction here examined.

PMID- 8293479
TI  - Centrosome repositioning immediately following karyokinesis and prior to
      cytokinesis.
AB  - The behaviour of the centrosome immediately following cell division in tissue
      culture cells has been investigated. We find that following karyokinesis, but
      preceding cytokinesis, sister centrosomes relocate from the spindle poles to a
      position adjacent to the intercellular bridge. This repositioning is accompanied
      by the appearance of a microtubule bundle that extends from the poleward region
      of the cell to the centrosome and increases in length as the centrosome
      approaches the intercellular bridge. Disruption of this bundle with colcemid
      interrupts centrosome repositioning. In contrast, centrosome repositioning
      persists in late mitotic cells grown in the presence of cytochalasin D. However,
      the position of the microtubule-centrosome complex within the cell is randomized
      suggesting that the path, but not the process, of centrosome repositioning is
      dependent on an intact actin filament network. This study points out, for the
      first time, that the complex migration of the centrosome preceding mitosis is
      paralleled by an equally complex set of events following cell division. We
      suggest that post-mitotic centrosome repositioning may play a role in ensuring
      that daughter cells have equal but opposite polarity and may reflect an
      interrelationship between the establishment of the interphase cytoskeleton and
      the completion of cytokinesis.

PMID- 8293478
TI  - gCap39 is a nuclear and cytoplasmic protein.
AB  - gCap39 is a newly identified member of the Ca(2+)- and polyphosphoinositide
      modulated gelsolin family of actin binding proteins which is different from
      gelsolin in several important respects: it caps filament ends, it does not sever
      filaments, it binds reversibly to actin, it is phosphorylated in vivo, and it is
      also present in the nucleus. gCap39 and gelsolin coexist in a variety of cells.
      To better understand the roles of gCap39 and gelsolin, we have compared their
      relative amounts and intracellular distributions. We found that gCap39 is very
      abundant in macrophages (accounting for 0.6% of total macrophage proteins), and
      is present in 12-fold molar excess to gelsolin. Both proteins are highly induced
      during differentiation of the promyelocytic leukemia cell line into macrophages.
      gCap39 is less abundant in fibroblasts (0.04% total proteins) and is present in
      equal molar ratio to gelsolin. The two proteins are colocalized in the cytoplasm,
      but gCap39 is also found in the nucleus while gelsolin is not. Nuclear gCap39
      redistributes throughout the cytoplasm during mitosis and is excluded from
      regions containing chromosomes. Our results demonstrate that gCap39 is a nuclear
      and cytoplasmic protein which has unique as well as common functions compared
      with gelsolin.

PMID- 8293480
TI  - In vitro functional characterization of bacterially expressed human fibroblast
      tropomyosin isoforms and their chimeric mutants.
AB  - At least eight tropomyosin isoforms (hTM1, hTM2, hTM3, hTM4, hTM5, hTM5a, hTM5b,
      and hTMsm alpha) are expressed from four distinct genes in human fibroblasts. In
      order to elucidate isoform properties, we have subcloned hTM3 and hTM5 full
      length cDNAs, as well as their chimeric cDNAs into the bacterial expression pET8C
      system. Bacterially expressed tropomyosin isoforms (called PEThTM3, PEThTM5,
      PEThTM5/3, and PEThTM3/5) were purified and characterized. Under optimal binding
      conditions, the binding of PEThTM5 isoform to F-actin was stronger than the
      PEThTM3 isoform. However, analysis of actin-binding by the McGhee and von Hippel
      equation revealed that PEThTM3 exhibits higher cooperativity in binding than
      PEThTM5 does. Furthermore, the chimera PEThTM5/3 which possessed the N-terminal
      fragment of hTM5 fused to the C-terminal fragment of hTM3 had even stronger actin
      binding ability. The reverse chimera PEThTM3/5 which possessed the N-terminal
      fragment of hTM3 fused to the C-terminal fragment of hTM5 demonstrated greatly
      reduced affinity to actin filaments. In addition, both chimeras had different KCl
      requirements for optimal binding to F-actin than their parental tropomyosins. A
      bacterially made C-terminal fragment of human fibroblast caldesmon (PETCaD39) and
      native chicken gizzard caldesmon were both able to enhance the actin-binding of
      these bacterially expressed tropomyosins. However, PETCaD39's enhancement of
      binding to F-actin was greater for PEThTM5 than PEThTM3. Under 30 mM KCl and 4 mM
      MgCl2, the low M(r) isoform PEThTM4 appeared to be able to amplify the actin
      activated HMM ATPase activity by 4.7 fold, while the high M(r) isoform PEThTM3
      stimulated the activity only 1.5 fold. The higher enhancement of ATPase activity
      by PEThTM5 than by PEThTM3 suggested that the low M(r) isoform hTM5 may be more
      involved in modulating nonmuscle cell motility than hTM3. These results further
      suggested that different isoforms of tropomyosin might have finite differences in
      their specific functions (e.g., cytoskeletal vs. motile) inside the cell.

PMID- 8293481
TI  - Effects of cytochalasin and colcemid on cortical flow in coelomocytes.
AB  - Sea urchin coelomyocytes naturally flatten on a substratum into a discoid
      morphology and display striking, centripetally directed cortical flow along the
      radii of the cell when viewed with time lapse, video enhanced microscopy. The
      rate of cortical flow averaged 4.5 microns/min in the peripheral most 10 microns
      of cytoplasm but slows considerably in the perinuclear region. Cytochalasin B
      causes: (1) the flow to stop, (2) the buildup of an actin filament-rich
      peripheral ridge of cytoskeletal material, (3) the centrifugal dissolution of a
      portion of the actin cytoskeleton, and (4) the contraction of other portions of
      the cytoskeleton into foci. Cytochalasin D (CD), on the other hand, causes the
      flowing actin meshwork to become severed from the edge of the cell and allows it
      to be drawn at least part way in towards the nucleus. A smaller peripheral ridge
      of actin filament buildup is also seen with CD. Colcemid induces another striking
      change in the cytoskeleton. The centripetal progression of the actin is not
      stopped by colcemid, but shortly after leaving the periphery of the cell, the
      linear elements within the flow become reoriented into arcs. The long axis of the
      arcs is roughly parallel with the cell's edge. The effects of all three drugs are
      reversible. The results are discussed in light of other systems and potential
      mechanisms for cortical flow.

PMID- 8293482
TI  - The cell biology of bone.
AB  - Bone remodelling and repair are accomplished by the co-ordinated activity of
      cells of the osteoclast and osteoblast lineages. Small changes in the balance
      between formation and resorption will, when magnified by repeated cycles, lead to
      significant reduction in bone mass and strength, ultimately resulting in
      fracture. This review focuses on the cellular features of bone remodelling and
      the known regulators of bone cell function. These include systemic and local
      factors, both soluble and contained within the complex extracellular matrix of
      bone.

PMID- 8293483
TI  - Bone mass and ageing.
AB  - Bone can be divided into two kinds of tissue, cortical and trabecular bone. The
      skeleton comprises approximately 80% cortical bone, mainly in peripheral bones,
      and 20% trabecular bone, mainly in the axial skeleton. Bone density increases
      with skeletal growth to a peak in late adolescence or early adulthood. Bone loss
      subsequently occurs with ageing in both sexes, and in females accelerated loss
      occurs at the menopause. The risk of osteoporotic fracture in later life is the
      result of peak bone mass achieved at skeletal maturity and subsequent age-related
      and postmenopausal bone loss. Peak bone mass is largely genetically determined
      but is also influenced by environmental factors such as dietary calcium and
      physical activity. Bone loss with ageing occurs at different rates and different
      times in different skeletal sites. Femoral neck bone loss probably occurs in a
      linear fashion throughout life from early adulthood but may be accelerated at the
      menopause. Spinal bone loss may commence before the menopause but is rapidly
      increased in the immediate postmenopausal years. Bone strength is directly
      related to bone density, but the loading force is also relevant to risk of
      fracture.

PMID- 8293484
TI  - Epidemiology and public health impact of osteoporosis.

PMID- 8293485
TI  - Measurement of bone mass and turnover.
AB  - Bone mass is the most important determinant of fracture risk. Current bone mass
      of an individual will be determined by the peak bone mass achieved in early adult
      life and the subsequent duration and rate of bone loss. In attempting to predict
      an individual's future risk of fracture it is therefore logical to attempt to
      assess both of these parameters. Serial measurements of bone mineral density and
      estimation of the rate of bone turnover may also be used to determine the
      response to treatment. In this chapter we review the currently available methods
      of measuring BMD and bone turnover, and discuss their place in the diagnosis and
      management of osteoporosis.

PMID- 8293486
TI  - Pathogenesis of postmenopausal osteoporosis.
AB  - Osteoporosis is a disorder of ageing that shares with other disorders of ageing a
      multifactorial pathogenesis. The important factors for osteoporosis include the
      diet, life-style and intercurrent factors such as disease. However, it is clear
      that loss of ovarian function is an important determinant of bone loss, and
      oestrogen appears to be the key factor involved. Thus, not only does loss of
      ovarian function result in bone loss, it can be stopped by adequate oestrogen
      intervention. Numerous techniques are available to measure bone mass non
      invasively and to estimate the risk of future fracture. Thus, for the
      postmenopausal woman who is concerned about osteoporosis, and who is willing to
      accept intervention to prevent the disease, bone mass measurement allows the
      clinician to determine the risk of future osteoporotic fracture and to provide
      intervention if required. Future studies may elucidate whether determination of
      skeletal remodelling using biochemistry adds significantly to risk determination.
      This may be required when considering agents other than oestrogen for
      intervention among asymptomatic women, as these agents primarily affect the
      skeleton, while the effects of oestrogen are wide ranging in the body.

PMID- 8293487
TI  - Secondary osteoporosis.
AB  - Osteoporosis with attendant increased fracture risk is a common complication of
      many other diseases. Indeed, almost all chronic diseases make some impact on life
      style, usually by restricting physical activity and hence reducing the anabolic
      effect of exercise and gravitational strains on the skeleton. Restricted appetite
      and modified gastrointestinal tract function is another commonplace finding that
      has an impact on bone nutrition and synthesis, as on other systems. Sex hormone
      status is of particular importance for the maintenance of the normal skeleton,
      and the postmenopausal woman is at particular risk for most causes of secondary
      osteoporosis. In dealing with secondary osteoporosis in the hypo-oestrogenic
      woman, the question of giving hormone replacement therapy in addition to other
      disease-specific therapy should always be considered, as, for example, in a young
      amenorrhoeic woman with Crohn's disease. Similarly, in hypogonadal men the
      administration of testosterone is useful for bone conservation. The wider
      availability of bone densitometry ought to make us more aware of the presence of
      osteoporosis in the many disease states discussed above. This is particularly
      important as the life span of such patients is now increased by improved
      management of the underlying disease process in many instances. Even in steroid
      induced osteoporosis--one of the commonest and most severe forms of osteoporosis-
      we now have some effective therapy in the form of the bisphosphonates and other
      anti-bone-resorbing drug classes. The possibility of prophylaxis against
      secondary osteoporosis has therefore become a possibility, although the very long
      term effects of such drug regimens are still unknown. In some situations, such as
      thyrotoxicosis, Cushing's syndrome and immobilization, spontaneous resolution of
      at least part of the osteoporosis is possible after cure of the underlying
      problem. The shorter the existence of the basic problem, the more successful the
      restoration of the skeleton appears to be. A useful credo for clinicians with
      respect to secondary osteoporosis is: to think of it; to use specific therapy for
      the underlying disease; to reduce or remove completely any relevant drug or toxic
      material; to optimize physical activity and general nutrition; to treat
      hypogonadism if present and feasible; and to consider the use of specific anti
      bone-resorbing or other bone active drugs.

PMID- 8293488
TI  - HRT and osteoporosis.
AB  - Hormone replacement therapy is well documented to reduce the increased bone
      turnover induced by oestrogen deficiency and, as a result, it prevents bone loss
      after the menopause. It has been shown that this effect leads to a significant
      reduction in osteoporotic fracture rates. There is a dose threshold effect, the
      duration of therapy influences the degree of benefit and, after the cessation of
      HRT, postmenopausal bone loss resumes. Women take HRT for many reasons, most for
      relief of menopausal symptoms, and 10-20% show poor compliance. The nature of HRT
      preparations is discussed and the current understanding of benefits and risks
      described.

PMID- 8293489
TI  - Alternatives to HRT in prevention and treatment.
AB  - Oestrogen hormone replacement therapy remains the first choice for the treatment
      and prevention of osteoporosis in postmenopausal women, but for patients who are
      unsuitable for this therapy, which of course includes men, other satisfactory
      treatments are available. Several placebo-controlled studies have demonstrated
      that bisphosphonates and calcitonin prevent bone loss or perhaps increase bone
      density over 2-3-year periods, and reduce the rate of fracture. It is not known
      whether these treatments will increase bone density over longer periods of time.
      Cyclical etidronate has recently become licensed in the UK for use in the
      treatment of osteoporosis, and it is hoped that other bisphosphonates and
      intranasal calcitonin will soon be added to the available treatments. Fluoride
      appears to increase bone density but, at doses above a very narrow therapeutic
      window, it increases the fracture rate, either because of bone redistribution,
      formation of poor quality bone or a toxic effect on osteoblasts. At present,
      fluoride remains a treatment to be used only under expert supervision or within
      the context of controlled clinical trials. Anabolic steroids may be of value in
      selected elderly patients with osteoporosis. The patient may be able to
      contribute to the prevention of osteoporotic fracture by exercising, which will
      improve dexterity and may have a small effect to increase bone density, and by
      avoiding the factors that predispose to falls, such as icy paths and excess
      alcohol. Changes in the diet are unlikely to play a major role in the maintenance
      of bone density in women living in the Western world.

PMID- 8293490
TI  - Prophylaxis of falls and treatment of fractures.
AB  - This review has highlighted important preventive measures for falls and fractures
      in elderly osteopenic patients, and has discussed the therapeutic possibilities
      after an osteoporotic fracture has occurred. Assuming that a large proportion of
      osteoporotic fractures are a consequence of traumatic falls, and are not
      spontaneous, due to osseous weakness, preventive measures in elderly people are
      best directed to counteract muscular weakness, improve agility and correct visual
      impairment. It is also important to guard against unnecessary obstacles in the
      home and the reflex habits of doctors to prescribe hypnotics and tranquillizers,
      as well as their occasional tendency to overtreat hypertension. Practical
      examples of rational measures to protect against these causes of fractures have
      been given. In the second part of the review, the treatment of fractures has been
      delineated. The goals are adequate pain relief, early immobilization of the
      patient, avoidance of overtreatment and fast restoration of the quality of life.
      Three stages of pain relief by drugs are outlined. The first consists of a simple
      non-narcotic analgesic, such as paracetamol. In a second stage, either the
      combination of paracetamol with a muscle relaxant or the administration of a
      narcotic analgesic of medium potency is proposed. As a third stage, several
      therapeutic approaches to the administration of potent narcotic analgesics have
      been discussed. Non-drug measures, such as the use of heat, ultra-soft
      mattresses, walking frames, crutches and sticks, as well as active forms of
      physiotherapy, have been discussed both in terms of pain relief and early
      mobilization.

PMID- 8293491
TI  - Corticosteroid osteoporosis.
AB  - Glucocorticoids produce osteoporosis via a number of mechanisms, the most
      important of which is probably inhibition of bone formation. This results in
      reduction in bone mass of 10-20% at commonly assessed sites, but the bone loss is
      30-40% when predominantly trabecular bone is measured. The dosage and duration of
      steroid treatment influence the extent of bone loss, but other factors are not
      predictive. At the present time, a patient who has demonstrable sex hormone
      deficiency should receive appropriate replacement therapy. Optimization of
      calcium intake is advisable. If bone loss is severe or continues in spite of
      these measures, the addition of a bisphosphonate, calcitonin, fluoride or a
      vitamin D metabolite may be appropriate, according to local availability.
      Thiazide diuretics can be combined with all of these regimens. If combined with
      vitamin D or its metabolites, careful monitoring of serum calcium levels should
      be undertaken. Bone density should be monitored annually until such time as it is
      stable.

PMID- 8293492
TI  - Osteoporosis in men.
AB  - Bone is lost with advancing age in men as in women, leading to an increased
      incidence of osteoporotic fractures of the fore-arm, vertebral body and femoral
      neck. By the ninth decade of life, 4% of men will have sustained a fore-arm
      fracture, 7% a vertebral fracture and 5% a femoral neck fracture. The absolute
      number of osteoporotic fractures is rising in men, because of the ageing
      population and an increase in the age-specific incidence of fractures. Even if
      the age-specific incidence of fractures stabilizes, demographic trends suggest
      that a further increase in the number of men with osteoporotic fractures is
      inevitable. Peak bone mass in men is influenced by race, hereditary, hormonal
      factors, physical activity and calcium intake during childhood and adolescence.
      Bone loss in men starts at about the age of 35 years and is regulated by genetic,
      endocrine, mechanical and nutritional factors. Secondary causes of osteoporosis
      may be detected in about 55% of men with vertebral crush fractures. The major
      causes are steroid therapy, hypogonadism, skeletal metastases, multiple myeloma,
      gastric surgery and anticonvulsant treatment. Hypogonadism is found in up to 20%
      of men with vertebral crush fractures, although the clinical features of
      testosterone deficiency may not always be present. Hypogonadal osteoporosis is
      associated with increased bone resorption and decreased mineralization, which is
      reversed by treatment with testosterone, leading to an increase in bone density.
      There is little published information on the treatment of primary osteoporosis in
      men. Although calcitonin, bisphosphonates and testosterone may be effective in
      the management of osteoporosis in men, confirmation is required in formal
      clinical trials.

PMID- 8293493
TI  - Osteoporosis prevention through screening: will it be cost effective?

PMID- 8293494
TI  - Osteoporosis: current controversies and future trends.

PMID- 8293495
TI  - Regulation of liver-specific gene expression.

PMID- 8293496
TI  - Nucleolar morphological rearrangement related to transcriptional and replicative
      state in Burkitt lymphoma cells.
AB  - The specific silver staining of nucleolar region organizers was applied to Daudi
      lymphoma control and interferon alpha-treated cells. Isolated nuclei from control
      and treated samples were used for the kinetic analysis of in vitro RNA and DNA
      synthesis. Results have shown that interferon treatment induces a reduction of
      the transcriptional and replicative activities within 90 min. Concomitant to
      these results is the modification of the organization of nucleoli. Intensity and
      distribution of silver grains are, in fact, different in treated cells nucleoli
      as compared to those of controls. Thus, the number and the arrangement of
      granules could be related to the functional state of the cells suggesting that
      the transient cascade of interferon-generated signals involves also modulation of
      nucleolar structure and function in accordance with the hypothesis of a
      relationship of cell proliferation rate to silver-stained nucleolar protein
      quantity.

PMID- 8293497
TI  - Assembly of envelope structure with vesicles associated with Ku-homologous
      protein in Xenopus egg extract in the absence of chromatin.
AB  - To study the process of nuclear envelope assembly at the end of mitosis, we
      developed a chromatin-free in vitro system for assembly of envelope structures in
      Xenopus interphase egg extract, and examined the participation of Ku-homologous
      protein in the assembly. The envelope structure assembled spontaneously in the
      absence of chromatin or DNA between glass plates under a condition that minimized
      generation of flow of the extract. Morphological study using an electron
      microscopy has revealed that the membrane surrounding the envelope structure is a
      double membrane that contains gaps resembling nuclear pore complex. Their
      assembly was dependent on ATP and was inhibited by the addition of GTP-gamma-S or
      N-ethylmaleimide. Depletion of a pre-nuclear vesicle by preincubating the
      interphase egg extracts with large excess of sperm head chromatins impaired the
      assembly. The membrane vesicle, which was associated with Ku-homologous protein
      of Xenopus, participated in the assembly as proven by reaction with monoclonal
      antibody made specific for Ku p70 protein. However, the assembly process of the
      envelope structure was inhibited only slightly by the antibody, suggesting that
      the Ku-homologous protein does not participate in the fusion process of vesicles
      to form the envelope structure.

PMID- 8293498
TI  - Serum-mediated modification of proliferation in factor-dependent macrophage cell
      lines.
AB  - Previously we described that bacterial lipopolysaccharide (LPS) promoted DNA
      synthesis and supported the cell viability in the factor-dependent macrophage
      cell lines BDM-1 and BDM-1W3 in the absence of colony-stimulating factor (CSF).
      To further examine this phenomenon, in the present study we examined the effects
      of serum on CSF-dependent proliferation and LPS-induced DNA synthesis in BDM-1
      and BDM-1W3 cells. Fetal calf serum (FCS) was required for CSF-dependent
      proliferation in BDM-1 and BDM-1W3 cells. FCS was also required for LPS-induced
      DNA synthesis in BDM-1W3 cells. However, at concentrations higher than 0.2%, FCS
      inhibited LPS-induced DNA synthesis in BDM-1W3 cells in a dose-dependent manner.
      To obtain the inhibitory activity in FCS (FCS-In) for LPS-induced DNA synthesis,
      FCS was fractionated by gel filtration chromatography using Sephacryl S-200,
      chromatography on DEAE-Sephacel, and affinity chromatography on heparin
      Sepharose. FCS-In was eluted in the void volume peak from a Sephacryl S-200
      column, indicating that FCS-In has a molecular weight of more than 250,000. The
      molecular weight of FCS-In was apparently 270,000 as determined by SDS
      polyacrylamide gel electrophoresis (PAGE) under non-reducing conditions. Upon
      reduction, four components became detectable with apparent molecular weights of
      170,000, 110,000, 67,000, and 30,000. The inhibitory activity in FCS-In material
      was inactivated by heat and trypsin treatment. The partially purified FCS-In
      inhibited LPS-induced DNA synthesis in BDM-1W3 cells, but did not inhibit the
      proliferation of BDM-1W3 cells induced by IL-3, granulocyte-macrophage CSF (GM
      CSF), or macrophage CSF (M-CSF).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293499
TI  - Mapping of the 70 kDa, 34 kDa, and 11 kDa subunit genes of the human multimeric
      single-stranded DNA binding protein (hSSB/RPA) to chromosome bands 17p13, 1p35
      p36.1, and 7p21-p22.
AB  - Human single-stranded DNA binding protein (hSSB/RPA) is a multimeric single
      stranded DNA binding protein consisting of three subunits of 70 kDa, 34 kDa, and
      11 kDa. Human SSB was isolated from HeLa cells as an essential factor for the in
      vitro replication of simian virus 40 DNA. We and others have isolated and
      sequenced cDNAs for each subunit of the SSB. The chromosome on which each gene is
      located was determined through the analysis of a panel of human/hamster somatic
      cell hybrids using the polymerase chain reaction with pairs of synthetic
      oligonucleotide primers from the 3'-untranslated sequences of the genes. Genomic
      clones for each gene were isolated from a genomic cosmid library prepared from
      human lymphoblastoid cells. Using those clones as probes, we have carried out
      fluorescence in situ hybridization to human metaphase chromosomes and have mapped
      the 70 kDa subunit gene to 17p13, the 34 kDa subunit gene to 1p35-p36.1, and the
      11 kDa subunit gene to 7p21-p22. Since hSSB participates in replication,
      recombination and repair of DNA, the physical mapping of hSSB genes may aid in
      the identification of human hereditary diseases associated with aberrant DNA
      reactions caused by genetic alterations of the hSSB.

PMID- 8293500
TI  - Altered sensitivities to potential inhibitors of cholesterol biosynthesis in
      Niemann-Pick type C fibroblasts.
AB  - Cultured fibroblasts from patients with Niemann-Pick disease type C (NP-C) are
      characterized by the lysosomal accumulation of unesterified cholesterol and the
      inability of low-density lipoprotein (LDL) to stimulate cholesterol
      esterification, in addition to impaired LDL-mediated down-regulation of LDL
      receptor activity and cellular cholesterol synthesis. Although a defect in the
      transport of cholesterol from lysosomes to other intracellular membrane sites has
      been suggested, it is unclear how cells regulate the levels of cellular sterols
      and whether their membrane cholesterol requirements are satisfied or not. We
      studied the esterification of exogenously added cholesterol, total levels of
      cellular cholesterol and cholesteryl ester, cholesterol synthesis from a two
      carbon precursor, and sensitivities to potential inhibitors of cholesterol
      biosynthesis in proliferating NP-C cells. We observed the following: (a)
      esterification of [3H]cholesterol was decreased but the total amount of cellular
      cholesteryl ester was not decreased; (b) synthesis of cholesterol from
      [3H]acetate was increased; and (c) cells were hypersensitive to cholecalciferol,
      an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, and were resistant to
      filipin, which binds to membrane sterols and presumably damages the membrane. The
      results indicate that NP-C cells depend on the cellular cholesterol synthetic
      pathway for their proliferation, but the plasma membrane sterols are presumably
      decreased. The altered sensitivities to potential inhibitors of cholesterol
      biosynthesis should be a useful marker for diagnosis and genetic studies.

PMID- 8293501
TI  - Brefeldin A protects ricin-induced cytotoxicity in human cancer KB cell line, but
      not in its resistant counterpart with altered Golgi structures.
AB  - Brefeldin A (BFA), an isoprenoid fungal metabolite, dramatically disrupts
      intracellular protein transport and protein secretion. BFA protects cells from
      the cytotoxicity of a plant toxin, ricin or pseudomonas toxin, but not that of
      diphtheria toxin (Yoshida et al., 1991. Expt. Cell Res., 192: 389-395.). In this
      study, we examined whether BFA could differentially change the cytotoxicity of
      ricin between BFA-sensitive cells and BFA-resistant cells. As a BFA-resistant
      cell line, we used a resistant cell line, KB/BF2-2, derived from BFA-sensitive
      human cancer KB cells. BFA treatment caused the disappearance of typical Golgi
      cisternae and the concomitant appearance of dilated vesicles in the cytoplasm in
      KB cells. By contrast, KB/BF2-2 cells had already altered Golgi structures with
      poor development of cisternae and also many vesicles in the absence of BFA, and
      BFA treatment did not further induce the morphological changes. Although a plasma
      membrane-specific marker protein, alpha-adaptin, was localized similarly in
      KB/BF2-2 as KB, Golgi specific markers such as beta-cop and gamma-adaptin were
      distributed in the cytoplasmic small vesicles as well as Golgi compartments in
      KB/BF2-2 cells in the absence of BFA, and the mutant cells showed no apparent
      changes in the distribution even when exposed to BFA. Ricin inhibited protein
      synthesis in KB and KB/BF2-2 to similar levels while pretreatment of KB cells
      with BFA at 0.1 microgram/ml almost completely reversed the inhibitory effect of
      ricin. By contrast, the pre-exposure of KB/BF2-2 cells to 1.0 microgram/ml BFA
      only partially rescued the ricin-induced inhibition of protein synthesis.
      Exposure to BFA at 30 min before ricin addition or at 0 min with ricin rescued
      the protein synthesis inhibition, but no rescue occurred when BFA was added 30
      min after ricin addition. BFA could not rescue the protein synthesis inhibition
      by another toxin, diphtheria toxin. Our results suggest that BFA-resistant
      mutation causes a specific change in the endocytic membrane traffic of ricin in
      human cells, and also that cytotoxicity of diphtheria toxin does not share a
      common pathway of the intracellular transport with that of ricin.

PMID- 8293502
TI  - Molecular characterization of extrachromosomal circular DNAs from an embryonal
      carcinoma cell line induced to differentiate into neuron-like cells in vitro.
AB  - Extrachromosomal circular DNAs isolated from a P19 embryonal carcinoma cell line
      were induced to differentiate into neuron-like cells by retinoic acid and cloned
      into an EcoRI site of a phage vector. Of the 26 DNA inserts (2.1 kb in average
      length) analyzed, 16 contained repetitive sequences. Out of 10 DNA inserts with
      unique sequence, 6 carried linear chromosomal sequences and 4 showed chromosomal
      rearrangements in Southern blots. Two unique fragments with germline
      configuration were enriched in circular DNA clone libraries. We assigned the
      breakpoints of 3 circular DNA fragments to positions in the germline sequence.
      Patchy short inverted repeats were found in the vicinity of breakpoints. An
      intrastrand loop structure between such inverted short homology region may be
      required for the circularization of excised DNA.

PMID- 8293503
TI  - [Diagnosis and therapy in fetuses at risk in Rh isoimmunization].
AB  - The objective of the work was to evaluate the importance of antenatal examination
      of amniotic fluid and foetal blood in case of suspected Rh isoimmunization of the
      foetus. In 1991-1992 in 16 patients with a rise of the titre of anti-D antibodies
      to > 1:8 between the 24th and 36th week of gestation 32 punctures of the
      umbilicus by means of a 22 gauge needle were made under continual ultrasonic
      control. In two instances intraumbilical transfusion was indicated. The authors
      revealed that with the rising titre of anti-D antibodies in maternal blood the
      foetal haematocrit value in the umbilical blood declines. With the rising
      bilirubin level the haematocrit declines. In foetuses with a haematocrit of < 31%
      severe forms of jaundice are encountered more frequently with the necessity of
      long-term phototherapy and exchange transfusion. The authors did not find a
      correlation between the haematocrit of foetal blood and the bilirubinoid
      concentration in amniotic fluid, assessed by Liley's method. Foetuses with a
      haematocrit higher than 31% are not threatened by severe forms of jaundice and
      therefore the authors do not use transfusions in these foetuses. Based on
      hitherto assembled experience, the authors confirmed that cordocentesis is
      associated with a comparable risk as amniocentesis but provides more accurate
      information on the state of the foetus.

PMID- 8293504
TI  - [Prenatal cytogenetic diagnosis in older pregnant women].
AB  - The paper deals with the genetic risk of advanced age of women assessed on the
      basis of prenatal cytogenetic analysis during the second trimester of gestation.
      The examined group comprised 614 pregnant women older than 35 years. The cells
      for chromosomal analysis were obtained by transabdominal amniocentesis during the
      16th to 18th week of gestation. Cytogenetic examination revealed that the general
      risk of an aneuploid foetus in women of more advanced age is 2.12% and the most
      frequently encountered chromosomal aberration was trisomy 21 which was confirmed
      in 1.30 cytogenetically examined foetuses.

PMID- 8293505
TI  - [Ripening the cervix using intracervical administration of PGE2 with a butterfly
      needle in terminating pregnancy].
AB  - By intracervical administration of 0.75 mg PGE2, using a butterfly needle, the
      authors preinduced 32 patients with an immature portio vaginalis cervicis (CS 5
      points) who had indications for termination of a full-term pregnancy. Slow
      administration lasted cca 6 hours. Maturation of the portio vaginalis cervicis
      occurred in 93.5%, in 71% regular uterine contractions started. The length of
      labour stages, the loss of blood, frequency of injuries during labour and foetal
      hypoxia were similar as in spontaneous deliveries. Side-effects were recorded in
      20.7%. The described method is a suitable alternative to administration of gel
      substances, in particular because it is cheaper because it is well tolerated by
      the patients and is simple.

PMID- 8293506
TI  - [Changes in hypophyseal-ovarian axis hormone levels in the first days after
      central nervous system surgery].
AB  - The authors examined the FSH, LH, prolactin, oestradiol and progesterone levels
      during the perioperative period in 14 women, mean age 35.7 years, who were
      subjected to intracranial operations. They found that during the first
      postoperative days the FSH level (p < or = 0.01), LH level (p < or = 0.01) and
      oestradiol level (p < or = 0.05) declined, while the progesterone and prolactin
      level do not change significantly. This is consistent with data in the literature
      on transient hypogonadotropic hypogonadism after head injuries or after
      operations and injuries of other organs. The disorder is only of a short-term
      character and does not lead to serious impairment of the menstrual cycle.

PMID- 8293507
TI  - [Epidemiology of malignant tumors of the uterus].
AB  - The authors describe the frequency, incidence, number of deaths and mortality
      from malignant tumours of the uterine corpus in the Czech Republic in 1961-1988.
      The mean incidence of 13.06 during the five-year period 1961-1965 rose to a mean
      incidence of 25.12 during the five-year period 1984-1988, while during this
      period a paradoxical decline of the mortality from 9.00 to 6.7 occurred. This
      implies a decline of the lethality during 1961-1965 from 76.56% to 28.98%, i.e.
      to 37.85% of the original value. The reasons of the decline in lethality may be
      earlier detection of the disease and possibly a rise in the incidence of less
      aggressive forms of hormone-dependent carcinomas only, because therapy did not
      change essentially during the mentioned period.

PMID- 8293508
TI  - [Knowledge of contraception in girls living in the region of Prague].

PMID- 8293510
TI  - [Uterine suturing in cesarean section].

PMID- 8293509
TI  - [Present possibilities of hormonal contraception].

PMID- 8293511
TI  - [Pregnancy and AIDS--the present situation in the Czech Republic].

PMID- 8293512
TI  - [The effect of tocolytic agents on the cardiovascular system of the mother, fetus
      and neonate].

PMID- 8293513
TI  - [Ovarian carcinoma and fertility].

PMID- 8293514
TI  - [Left-handedness and reproductive functions].

PMID- 8293515
TI  - [Errors and omissions].

PMID- 8293516
TI  - Effects of cholesterol on the miscibility of synthetic glucosamine diesters in
      lipid bilayers and the entrapment of superoxide dismutase into the positively
      charged liposomes.
AB  - Methyl-D-glucosamine-3,6-dilauroyl, dimyristoyl, dipalmitoyl or distearoyl esters
      were synthesized as positively charged lipids. They were incorporated into
      phosphatidylcholine liposomal membranes and the entrapment of superoxide
      dismutase (SOD) into the liposomes was attempted. The efficiency of the SOD
      entrapment into the positively charged multilamellar vesicles (MLVs), comprising
      egg yolk phosphatidylcholine and synthetic glucosamine diesters, was enhanced by
      the addition of cholesterol to the membranes. A differential scanning
      calorimetric study showed that the miscibility (solubility) of glucosamine
      diesters in phosphatidylcholine-bilayers increased on the addition of cholesterol
      to the membranes. Cholesterol assisted in the mixing of phosphatidylcholines with
      positively charged glucosamine diesters and increased the positive charges on the
      liposomal membranes. This was confirmed by incremental increases in the zeta
      potential of liposomal membranes with an increase in the cholesterol content.
      Entrapment of SOD thus became more efficient due to the enhanced electrostatic
      attraction between the positively charged membranes and the negatively charged
      SOD, and/or the electrostatic repulsive interactions between positively charged
      membranes; the latter interactions induced a thickening of the water layer in
      MLVs.

PMID- 8293517
TI  - Resin glycosides. XIX. Woodrosins I and II, ether-insoluble resin glycosides from
      the stems of Ipomoea tuberosa.
AB  - Two new ether-insoluble resin glycosides named woodrosins I and II were isolated
      from the stems of Ipomoea tuberosa L., and their structures were determined on
      the basis of chemical and spectral data. Contrary to anticipation, they had an
      intramolecular cyclic ester structure similar to that of ether-soluble resin
      glycosides (Mayer's jalapin) hitherto isolated. It is proposed to use the terms,
      "jalapin" and "convolvulin," not according to the solubility in ether (Mayer's
      classification), but according to the structure, i.e., intramolecular esters and
      others, respectively.

PMID- 8293518
TI  - Fungal metabolites. IX. Synthesis of a membrane-modifying peptide, hypelcin A
      III, from Hypocrea peltata.
AB  - A membrane-modifying peptide antibiotic having uncoupling activity on rat liver
      mitochondria, hypelcin A-III, has been synthesized by assembling five peptide
      fragments via the N,N'-dicyclohexylcarbodiimide method. The synthesized hypelcin
      A-III was identical with the natural product.

PMID- 8293519
TI  - Synthesis and mitogenic activity of chiral lipopeptide WS1279 and its
      derivatives.
AB  - Optically active lipopeptide derivatives have been synthesized by the use of
      chiral glycerol derivatives. Lipopeptide WS1279 derivatives with (R)-glycerol
      moieties showed a higher mitogenic activity than those with the (S)
      configuration. Various N-protected lipopeptide and N-deprotected derivatives
      showed increased mitogenic activity.

PMID- 8293520
TI  - Synthesis and evaluation of (piperidinomethylene)bis(phosphonic acid) derivatives
      as anti-osteoporosis agents.
AB  - Some (piperidinomethylene)bis(phosphonic acid) derivatives were prepared and
      their activity to inhibit a rise in serum calcium induced by parathyroid hormone
      in thyroparathyroidectomised rats was evaluated. Several (4-alkylidene-, 4,4
      dialkyl-, or 4-alkyl-4-halopiperidinomethylene)bis(phosphonic acid) derivatives
      showed considerable inhibitory activity. But compounds having aromatic and polar
      substituents such as azido, hydroxy, amino and amido on the piperidine ring were
      generally inactive. In this study, two 4-alkylidene compounds (8a and 8b) and a
      4,4-cyclic dialkyl compound (61) showed potent activity when administered either
      intravenously or perorally.

PMID- 8293521
TI  - Study on zwitter-ionization of drugs. II. Synthesis and pharmacological activity
      of some N-[3-(5H-dibenzo[a, d]cyclohepten-5-ylidene) propyl]-N-methylamino- and N
      [3-(6H-dibenz[b, e]oxepin-11-ylidene) propyl]-N-methylamino-alkanoic acid
      derivatives and related compounds.
AB  - A series of N-[3-(5H-dibenzo[a, d]cyclohepten-5-ylidene)propyl]-N-methylamino-
      (6a) and N-[3-(6H-dibenz-[b, e]oxepin-11-ylidene)propyl]-N-methylamino-alkanoic
      acid derivatives (6b) and related compounds (6c-f) were synthesized and examined
      for pharmacological activities in vitro, i.e., inhibitory effect on monoamine
      [noradrenaline (NA) and 5-hydroxytryptamine (5-HT)] uptake, inhibitory effect on
      5-HT-, histamine-, acetylcholine- and NA-induced contraction, and binding
      affinity for alpha 2-adrenoceptor and dopamine D2-receptor. In vitro tests
      indicated that zwitter-ionization was capable of maintaining H1-antihistaminic
      activity while greatly reducing other pharmacological activities. Further, 6a-f
      showed much stronger inhibitory effects on compound 48/80-induced lethality in
      rats than did the corresponding N,N-dimethylamines (2a-f). 3-[N-[3-(6H-Dibenz[b,
      e]oxepin-11-ylidene)propyl]-N-methylamino]- propionic acid (6b-2), selected as a
      candidate antiallergic agent of a new type, equally potent in rats and guinea
      pigs, exhibited strong inhibitory effects on 48 h homologous passive cutaneous
      anaphylaxis (PCA) in rats (ED50 = 0.019 mg/kg, p.o.) and on histamine-induced
      bronchoconstriction in anesthetized guinea-pigs (ED50 = 0.0067 mg/kg, p.o.).

PMID- 8293522
TI  - Synthesis and characterization of 11C-labeled fluoroclorgyline: a monoamine
      oxidase A specific inhibitor for positron emission tomography.
AB  - A new radioligand for monoamine oxidase type A (MAO-A), [11C]fluoroclorgyline,
      was synthesized from its desmethyl precursor by N-methylation reaction using
      [11C]methyl iodide with a radiochemical yield of 75-85%. The radiochemical purity
      of the product was more than 99% and the specific radioactivity was 7.4-18.5
      GBq/micromol. The in vivo tissue distribution studies of [11C]fluoroclorgyline in
      mice demonstrated its high initial uptake and prolonged retention in the brain,
      comparable to those of [11C]clorgyline. A selective interaction with MAO-A in the
      accumulation of [11C]fluorclorgyline was confirmed by a competition experiment
      performed with the MAO-A specific inhibitor,clorgyline, and MAO-B specific
      inhibitor, l-deprenyl. These very desirable characteristics of
      [11C]fluoroclorgyline suggested that its 18F labeled counterpart,
      [18F]fluoroclorgyline, would have great potential as a longer-lived alternative
      to 11C labeled clorgyline for in vivo studies of MAO-A in the human brain with
      positron emission tomography (PET).

PMID- 8293523
TI  - The stability of a novel carbapenem antibiotic, meropenem (SM-7338), in a solid
      state formulation for injection.
AB  - A formulation of meropenem, a novel carbapenem antibiotic for injection, was
      developed as a vial filled with a mixture of meropenem and dried sodium
      carbonate. During the design phase, we studied the effect of water in the
      formulation on the stability of meropenem in the solid state. Meropenem is
      obtained as trihydrate, whose moisture content is 12.35% and is nonhygroscopic.
      Dehydrated meropenem, whose moisture content was 3.4%, took up moisture quickly
      even under low humidity (33% RH). Also, the chemical stability of dehydrated
      meropenem was poor compared with that of untreated meropenem, which is quite
      stable. Degradation of meropenem by free water was considered as a possible cause
      of the poor stability. Degradation of meropenem due to liberation of its crystal
      water to free water was also observed when meropenem was micronized by pneumatic
      pulverization. Crystal water of meropenem was found to stay bound and to be
      almost inert in the formulation. Thus, meropenem injection formulation is stable
      for long time at room temperature.

PMID- 8293524
TI  - Prostanoids and related compounds. VI. Synthesis of isoindolinone derivatives
      possessing inhibitory activity for thromboxane A2 analog (U-46619)-induced
      vasoconstriction.

PMID- 8293525
TI  - Saponins from Vietnamese ginseng, Panax vietnamensis Ha et Grushv. Collected in
      central Vietnam. I.
AB  - From rhizomes and roots of Panax vietnamensis Ha et Grushv., Araliaceae, commonly
      known as Vietnamese Ginseng, two new acetylate saponins named vina-ginsenoside-R1
      (13) and vina-ginsenoside-R2 (15) were isolated. On the basis of chemical and
      spectral data, 13 was formulated as monoacetyl 24(S)-pseudo-ginsenoside-F11 and
      15 was proved to be monoacetyl majonside-R2. Besides the two new saponins and
      beta-sitosteryl-3-O-beta-D-glucopyranoside, sixteen known saponins were also
      isolated and identified. Dammarane saponins:ginsenoside-Rh1 and 20(R)-ginsenoside
      Rh1 (1), ginsenosides-Rg1 (2), -Re (3), -Rd (6), -Rb3 (7), -Rb2 (8), -Rb1 (9),
      pseudo-ginsenoside-RS1 (= monoacetyl ginsenoside-Re, 4), notoginsenosides-R1 (5)
      and -Fa (10). Ocotillol-type saponins:pseudo-ginsenoside-RT4 (11), 24(S)-pseudo
      ginsenoside-F11 (12), majonosides-R1 (16) and -R2 (14). Oleanolic acid
      saponins:ginsenoside-Ro (= chikusetsusaponin V, 17) and hemsloside-Ma3 (18), a
      saponin previously isolated from a cucurbitaceous plant, Hemsleya macrosperma C.
      Y. Wu. Despite having large horizontally elongated rhizomes, the underground part
      of this plant contains mainly dammarane saponins and a small amount of oleanolic
      acid saponins. In addition, the yield of ocotillol-type saponins, especially
      majonoside-R2, is surprisingly very high (more than 5% and ca. half of the total
      yield of saponin). This characteristic saponin composition has made Vietnamese
      Ginseng an interesting species among Panax spp.

PMID- 8293526
TI  - Post-aromatic deoxygenation in polyketide biosynthesis: reduction of aromatic
      rings in the biosyntheses of fungal melanin and anthraquinone.
AB  - Two enzyme reactions involved in the post-aromatic deoxygenation process of
      fungal melanin and pigments were studied from the viewpoint of enzymic reduction
      of aromatic rings. Hydroxynaphthalene reductase that catalyzes reduction of the
      aromatic rings of 1,3,6,8-tetrahydroxynaphthalene and 1,3,8-trihydroxynapthalene
      was partially purified from Phialophora lagerbergii and characterized. Emodin
      deoxygenase of Pyrenochaeta terrestris that catalyzes deoxygenation of emodin to
      afford chrysophanol was found to be resolved into two protein fractions with DEAE
      cellulose column. The two protein fractions acted synergistically in regard to
      emodin deoxygenase activity.

PMID- 8293527
TI  - Amino acids and peptides. XXXVI. Synthesis of enkephalin chloromethyl ketone and
      evaluation of its inhibitory activity against endopeptidase 22.19.
AB  - Boc-Tyr-Gly-Gly-Phe-Leu-Ch2Cl was synthesized by the conventional solution
      method. During the course of acid hydrolysis (6N HCl, 110 degrees C, 18h) of Boc
      Phe-Leu-CH2Cl, side reaction occurred, resulting in low recovery of Phe residue
      on amino acid analysis. The inhibitory activity of the synthesized Boc-Tyr-Gly
      Gly-Phe-Leu-CH2Cl against endopeptidase 22.19, an enzyme related to the
      metabolism of opioid peptides, was examined.

PMID- 8293528
TI  - Studies on antiinflammatory agents. III. Synthesis and pharmacological properties
      of metabolites of 4'-acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide
      (FK3311).
AB  - We synthesized putative metabolites of 4'-acetyl-2'-(2,4
      difluorophenoxy)methanesulfonanilide (FK3311, 1), a novel antiinflammatory agent,
      in order to confirm their structures and also to investigate their
      pharmacological properties. The structures of the metabolites 2-5 were confirmed
      by direct comparison with the synthesized authentic compounds. We employed the
      following tests to assess pharmacological activities: zymosan-induced
      prostaglandin E2 production for in vitro activity, adjuvant-induced arthritis for
      antiinflammatory activity, and acetic acid-induced writhing for analgesic
      activity. Metabolite 2 is nearly equipotent to 1 in the in vivo tests and
      metabolite 3 is an active metabolite with in vitro activity comparable to that of
      1.

PMID- 8293529
TI  - Amino acids and peptides. XIX. Preparation of enkephalin-poly(ethylene glycol)
      hybrid and evaluation of its analgesic activity.
AB  - The poly(ethylene glycol) hybrid of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) was
      prepared and its analgesic activity was examined. Poly(ethylene glycol) #4000 was
      converted to amino-poly(ethylene glycol) and coupled with the N alpha-protected
      pentapeptide, followed by trifluoroacetic acid treatment to give the hybrid. The
      hybrid was soluble in water or various organic solvents. The analgesic activity
      of Leu-enkephalin was markedly potentiated by hybrid formation with poly(ethylene
      glycol).

PMID- 8293530
TI  - Particle size effect of metastable calcium phosphates on crushing strength of
      self-setting bioactive calcium phosphate cement.
AB  - The resistance to crushing after a self-setting bioactive calcium phosphate
      cement, consisting of various particle sizes of tetracalcium phosphate (TECP),
      dicalcium phosphate dihydrate (DCPD) and hydroxyapatite (HAP), had hardened was
      tested after setting at 37 degrees C, 100% RH. X-ray diffraction suggested that
      the cement containing fine particles of DCPD and TECP was completely transformed
      to HAP, but that containing larger particles was not. Since particle size of both
      DCPD and TECP affected the dissolution rate, the crystal growth of HAP during
      cement formation depended on the specific surface area (Sw) of the raw materials.
      The crushing strength of the cement after hardening increased with an increase of
      its Sw.

PMID- 8293531
TI  - Total synthesis of octasaccharide related to glycosphingolipid from the
      spermatozoa of bivalves.

PMID- 8293532
TI  - Formation and property of mixed vesicles of phosphatidylcholine and MDP
      derivatives.
AB  - The aggregation form of mixtures of phosphatidylcholine and MDP derivatives was
      studied. The mixed vesicles containing less than 40% of B30-MDP were unilamellar,
      and over 40% B30-MDP aggregates of mixed vesicles or oligolammellar vesicles
      appeared. The mixed vesicles containing less than 20% of DV-7401 were
      unilamellar, and over 20% of it fibriform structures appeared.

PMID- 8293533
TI  - Elatosides A and B, potent inhibitors of ethanol absorption in rats from the bark
      of Aralia elata Seem: the structure-activity relationships of oleanolic acid
      oligoglycosides.
AB  - By monitoring the inhibitory effect on ethanol absorption in rats, new active
      saponins named elatosides A and B were isolated from the bark of Aralia elata
      Seem. together with elatosides C and D. The structures of elatosides A, B, C, and
      D were elucidated on the basis of chemical and physicochemical evidence. The
      inhibitory effects of several oleanolic acid oligoglycosides on ethanol
      absorption have been examined and some structure-activity relationships have been
      found.

PMID- 8293534
TI  - p53 mutations at A:T base pairs in angiosarcomas of vinyl chloride-exposed
      factory workers.
AB  - Mutations in the p53 tumor suppressor gene are commonly found in the major human
      cancers and the mutational spectrum in some cancer types is consistent with the
      genotoxic effects of the associated environmental risk factors. Thus far there is
      little information on p53 mutations in cancers of factory workers with a history
      of carcinogen exposure in the workplace. Occupational exposure to vinyl chloride
      causes liver angiosarcomas (ASL) and also increases the risk of several other
      cancers. Loss of p53 function in osteo- and fibrosarcomas can occur by two
      different mechanisms, p53 mutation and amplification of the MDM2 gene. We
      examined tumors from five vinyl chloride-exposed patients, four with ASL and one
      with hepatocellular carcinoma (HCC), for evidence of MDM2 proto-oncogene
      amplification or p53 mutation in exons 5-8. Amplification of MDM2 was not found,
      but in two of the angiosarcomas an A:T to T:A missense mutation was detected. p53
      sequence analysis of vinyl chloride associated cancers may provide valuable
      information on the relationship between carcinogen exposure and DNA damage in
      cancer-related genes.

PMID- 8293535
TI  - Reserpine-induced cell transformation without detectable genetic effects in
      Syrian hamster embryo cells in culture.
AB  - Reserpine, a naturally occurring rauwolfia alkaloid, used mainly as an
      antihypertensive drug, was examined for its ability to induce cell transformation
      and genetic effects in Syrian hamster embryo (SHE) cells in culture. Treatment of
      SHE cells with 2 micrograms/ml of reserpine had no effect on cell growth, while 4
      micrograms/ml of reserpine reduced the growth rate slightly and 8 micrograms/ml
      resulted in a significant inhibition of cell growth. Reserpine at doses of 4-8
      micrograms/ml for 48 h induced a dose-related increase in morphological
      transformation of the cells. Reserpine-transformed colonies were morphologically
      indistinguishable from colonies transformed with benzo[a]pyrene (B[a]P) or other
      chemical carcinogens. Over the dose range that resulted in cell transformation,
      treatment of SHE cells with reserpine failed to induce any detectable gene
      mutations at two genetic loci, chromosomal abnormalities including structural and
      numerical changes, or DNA adduct formation. These findings indicate that
      reserpine may have carcinogenic potential by unknown mechanisms that do not
      include direct induction of gene and/or chromosome mutations.

PMID- 8293536
TI  - In vivo binding of 1-nitropyrene to albumin in the rat.
AB  - Human risk assessment from exposure to nitropolynuclear aromatic hydrocarbons
      (NO2-PAH) has not been clearly defined, despite the widespread occurrence of such
      agents in the environment and their possible involvement in the etiology of some
      human cancers. This study was conducted since methods to determine exposure to
      and uptake of metabolically activated NO2-PAH are lacking. 1-Nitropyrene (1-NP),
      the most abundant and most extensively studied NO2-PAH, was found to bind to rat
      albumin at a level of 0.04 +/- 0.01% (mean +/- SD, n = 3) of the dose
      administered by gavage; the binding was linear over five orders of magnitude (P <
      0.01). The adducts cleared at a rate (half-life = 60 h) similar to that of the
      unmodified rat albumin. Chromatographic analysis revealed that albumin adducts
      could be resolved further into a major and a minor component. Mild acid
      hydrolysis of the major 1-NP-albumin adduct yielded phenolic derivatives that,
      when subjected to acetylation, produced a material with a mass spectrum similar
      to that of a synthetically prepared mixture, consisting of more than one isomer,
      1-acetylamino-X,Y-diacetoxypyrenes (chromatographic separation of the individual
      isomers was not achieved). Thus, this phenolic material that is released upon the
      acid treatment of albumin adducts may be a suitable indicator(s) for monitoring
      exposure to and metabolic activation of 1-NP.

PMID- 8293537
TI  - Expression of L- and M2-pyruvate kinases in proliferating oval cells and
      cholangiocellular lesions developing in the livers of rats fed a methyl-deficient
      diet.
AB  - Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing
      0.1% w/w DL-ethionine (CDE) for up to 22 weeks. The expression of the pyruvate
      kinase isoenzymes L (L-PK) and M2 (M2-PK) was immunohistochemically analyzed in
      liver slices from rats killed 4, 10, 14 and 22 weeks after starting the
      treatment. M2-PK was detected in bile duct epithelial cells of untreated rats and
      in proliferating oval cells, cholangiofibroses and cholangiofibromas of CDE-fed
      animals. Thus, M2-PK can be viewed as a positive marker of the bile duct
      epithelial/oval cell compartment. L-PK, a parenchymal cell-specific protein in
      untreated rat liver, was not present in proliferating oval cells, but was
      consistently observed in cells that were part of the ductal structures in the
      cholangiofibroses and cholangiofibromas. Based on their morphology, the L-PK
      positive duct cells were undoubtedly part of the bile duct epithelial cell
      lineage and no L-PK-positive hepatocyte-like cells were observed in the ducts.
      Hence, this study clearly shows that the mere presence of a liver parenchymal
      cell marker in cells of the bile duct epithelial/oval cell compartment does not
      necessarily preclude that these cells are undergoing a differentiation into
      preneoplastic parenchymal cells, as has previously been suggested.

PMID- 8293538
TI  - Mouse skin papilloma formation by chronic dermal application of 7,12
      dimethylbenz[a]anthracene is not reduced by diet restriction.
AB  - Diet restriction has repeatedly been shown to reduce the incidence of spontaneous
      and chemically induced tumors in rodents. However, no conclusive data are
      available to show whether carcinogenesis by chronic exposure to a genotoxic agent
      can also be retarded. In this study, diet restriction to 70% was investigated for
      a protective effect on the formation of skin papilloma in male NMRI mice treated
      twice weekly with 20 nmol 7,12-dimethylbenz[a]anthracene (DMBA). Rather
      surprisingly, no protection was seen. Both time of onset of papilloma formation
      (13 weeks in both groups) and time of 50% cumulative incidence (t50; 17.5 and 18
      weeks) were similar in the unrestricted and the restricted group. In contrast, a
      clearly protective effect was found in mice initiated with 100 nmol DMBA and
      promoted twice weekly with 2.5 nmol 12-O-tetradecanoylphorbol-13-acetate: the
      onset of papilloma formation increased from 7 to 11.5 weeks, the t50 was shifted
      from 8.5 to 19 weeks. Diet restriction, therefore, was not protective under
      conditions of chronic exposure to a genotoxic carcinogen. It cannot be considered
      a universal measure of cancer prevention.

PMID- 8293539
TI  - High survival rate of hamsters given intratracheal instillations of
      benzo[a]pyrene and ferric oxide and kept on a high beta-carotene diet.
AB  - The study described in this paper was primarily conducted to identify the cell
      types involved in the formation, progression and regression of metaplastic
      changes in the respiratory tract epithelium of hamsters after intratracheal
      intubations with benzo[a]pyrene. Furthermore, the role of vitamin A and beta
      carotene in these processes was studied. In the course of the study a remarkable
      effect of dietary beta-carotene on survival of hamsters became a subject of
      investigation. Hamsters were fed diets with various levels of vitamin A or beta
      carotene and were treated intratracheally with a suspension of benzo[a]pyrene
      with ferric oxide in saline. The tumour response of the respiratory tract was
      very low (2.8%) and hyper- and metaplasia of respiratory epithelium were
      virtually absent. However, an interesting observation was an exceptionally low
      mortality of only 2% after 69 weeks in the group of hamsters fed a high beta
      carotene diet (1% w/w), whereas in the other groups mortality after 69 weeks
      amounted to 25%. Although the exact cause of death of most of the hamsters could
      not be established, a 40% reduction of lipid peroxidation in the livers was found
      in the high beta-carotene group. Moreover, in this group the degree and incidence
      of nephrosis and of focal mineralization of kidneys and heart were lower than in
      the other groups. These favourable effects of the high beta-carotene diet may
      have contributed to the unusually high survival rate in hamsters fed this diet.
      Further studies are planned to verify and study this observation.

PMID- 8293540
TI  - DNA microfiltration assay: a simple technique for detecting DNA damage in
      mammalian cells.
AB  - A simple method for detection of DNA single-strand breaks (DNA-SSB) in cultured
      cells is described, based on filtration of alkaline-lysed cells through
      microfilters. After exposure to potentially DNA damaging agents, the cells are
      transferred to 0.8 micron cellulose acetate filters mounted in microfilter
      devices where they are washed, lysed and centrifuged to separate undamaged DNA
      from damaged DNA. When human bronchiolar cells (14Br) were exposed to different
      DNA damaging agents, hydrogen peroxide, N-methyl-N-nitro-N-nitrosoguanidine or 4
      nitroquinoline-1-oxide, there was good correlation between the extent of DNA
      damage assessed by this filtration technique and by DNA precipitation assay. DNA
      SSB were also detected by the filtration technique after exposure of bronchiolar
      cells to phorbol ester-stimulated human neutrophils. The filtration assay is easy
      to perform, the sample handling capacity is very high, and no expensive or
      complicated laboratory equipment is required. It may therefore be an alternative,
      or a complement, to other methods for detection of DNA-SSB.

PMID- 8293541
TI  - 12-O-tetradecanoylphorbol-13-acetate and the induction of prostaglandin E2
      generation by human keratinocytes: a re-evaluation.
AB  - 12-O-Tetradecanoylphorbol-13-acetate (TPA) induces prostaglandin E2 (PGE2)
      synthesis in mouse keratinocytes and is associated with the induction of
      keratinocyte proliferation as well as accelerated differentiation. In human
      keratinocytes, TPA has been reported not to induce the release of either 3H
      labeled arachidonic acid or 3H-labeled prostaglandins, even though cell
      differentiation is stimulated. Because PGE2 has been associated with the
      modulation of cell differentiation and because of technical problems inherent in
      evaluating arachidonic acid metabolism using only radiolabeled substrates, we
      evaluated the ability of TPA to induce endogenous PGE2 generation by cultured
      human keratinocytes using a specific and sensitive enzyme immunoassay. With this
      technique, TPA was found to induce a dose-dependent (1.6 x 10(-12)-1.6 x 10(-8)
      M) increase in PGE2 generation. These results are consistent with observations
      made not only in mouse keratinocytes but in other mammalian and human cell types.
      Documenting the ability of TPA to stimulate PGE2 production in human
      keratinocytes is very relevant to current theories regarding the role of PGE2 in
      keratinocyte differentiation as well as to establishing parallels between the
      murine and human skin models.

PMID- 8293542
TI  - Chemoprevention of mouse urinary bladder carcinogenesis by the naturally
      occurring carotenoid astaxanthin.
AB  - The chemopreventive effects of two xanthophylls, astaxanthin (AX) and
      canthaxanthin (CX), on urinary bladder carcinogenesis induced by N-butyl-N(4
      hydroxybutyl)nitrosamine (OH-BBN) was investigated in male ICR mice. Mice were
      given 250 p.p.m. OH-BBN in drinking water for 20 weeks and after a 1 week
      interval with tap water, water containing AX or CX at a concentration of 50
      p.p.m. was administered during subsequent 20 weeks. Other groups of mice were
      treated with AX or CX alone or untreated. At the end of the study (week 41), the
      incidences of preneoplastic lesions and neoplasms in the bladder of mice treated
      with OH-BBN and AX or CX were smaller than those of mice given OH-BBN. In
      particular, AX administration after OH-BBN exposure significantly reduced the
      incidence of bladder cancer (transitional cell carcinoma) (P < 0.003). However,
      the inhibition of the frequencies of such lesions in mice treated with OH-BBN and
      CX was not significant. Treatment with AX or CX also decreased the number/nucleus
      of silver-stained nucleolar organizer region proteins (AgNORs), a new index of
      cell proliferation, in the transitional epithelium exposed to OH-BBN.
      Preneoplasms and neoplasms induced by OH-BBN, and the antiproliferative
      potential, was greater for AX than CX. These results indicate that AX is a
      possible chemopreventive agent for bladder carcinogenesis and such an effect of
      AX may be partly due to suppression of cell proliferation.

PMID- 8293543
TI  - Isolation and identification of a new mutagen, 2-amino-4-hydroxy-methyl-3,8
      dimethylimidazo[4,5-f]quinoxaline (4-CH2OH-8-MeIQx), from beef extract.
AB  - By monitoring the mutagenicity to a new Salmonella tester strain, YG1024, which
      has a much higher level of O-acetyltransferase activity than S.typhimurium TA98,
      we found two new mutagenic compounds in bacteriological-grade beef extract. One
      of them (compound I), which had a similar UV spectrum to that of 2-amino-3,4,8
      trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), was isolated and shown to
      account for approximately 2% of the total mutagenicity of the materials adsorbed
      to blue cotton, and its concentration was estimated to be 6.0 ng/g beef extract.
      This amount of compound in beef extract was insufficient to allow measurements of
      various spectra, but its level was increased approximately 9-fold by heating beef
      extract with creatine and threonine at 200 degrees C for 5 h. From UV and mass
      spectra of the compound obtained from beef extract heated with creatine plus
      threonine, it was deduced to be a hydroxymethyl derivative of
      aminodimethylimidazo-quinoxaline. Compound I was isolated from the urine of rats
      given 4,8-DiMeIQx and identified as 2-amino-4-hydroxymethyl-3,8
      dimethylimidazo[4,5-f]quinoxaline (4-CH2OH-8-MeIQx) by 1H-NMR analysis. 4-CH2OH-8
      MeIQx induced 326,000 revertants of YG1024 and 99,000 revertants of TA98 per
      micrograms in the presence of S9 mix.

PMID- 8293544
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin as growth modulator in mouse hepatocytes with
      high and low affinity Ah receptor.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a highly potent tumor promoter in
      rodent liver, has been shown to increase epidermal growth factor (EGF)-stimulated
      DNA synthesis in rat hepatocytes in primary culture, a comitogenic effect
      possibly linked to the mechanism of liver tumor promotion. In hepatocytes
      isolated from male congenic mice (C57BL/6J) with high-affinity (AhbAhb) or low
      affinity (AhdAhd) Ah receptor the association of the comitogenic action of TCDD
      with the Ah receptor was investigated. The potency of TCDD as inducer of CYP1A
      catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity was approximately 10
      fold lower in AhdAhd compared to AhbAhb cells. In both cell types, TCDD did not
      stimulate DNA synthesis in the absence of EGF. When added together with EGF, TCDD
      exhibited two opposing effects on DNA synthesis, measured as incorporation of
      [3H]thymidine into DNA: (i) At 3 x 10(-14) M, TCDD increased EGF-stimulated DNA
      synthesis approximately 1.4-fold in AhbAhb but not in AhdAhd cells at a plating
      density of 35,000 cells/cm2. In hepatocytes from AhdAhd mice, 3 x 10(-12) M TCDD
      was required to elicit a similar comitogenic response. (ii) At a density of
      10,000 cells/cm2, 3 x 10(-12) M TCDD had a pronounced inhibitory effect on EGF
      stimulated DNA synthesis in AhbAhb but not in AhdAhd cells. Essentially similar
      results were obtained by counting of 5-bromo-2'-deoxyuridine-labeled nuclei.
      These findings demonstrate that TCDD can enhance or antagonize EGF-stimulated DNA
      synthesis in mouse hepatocytes modified by the cell density. The different
      concentration-response relationships in hepatocytes from both strains suggest
      that the Ah receptor regulates these responses.

PMID- 8293545
TI  - Association of deficient DNA repair during G2 phase with progression from benign
      to malignant state in a line of human skin keratinocytes transfected with ras
      oncogene.
AB  - Human skin keratinocytes after malignant neoplastic transformation by infection
      with Kirsten murine sarcoma virus (KiMSV) or transfection with pSV2 ras
      (containing an activated c-Ha-ras oncogene) showed a DNA repair deficiency(ies).
      The repair deficiency was manifest as an abnormally high frequency of chromatid
      breaks and gaps persisting after X-ray-induced DNA damage inflicted during the G2
      phase of the cell cycle. Non-tumorigenic control cells at that time were clearly
      repair-efficient. By analyzing benign and malignant tumorigenic HaCaT-ras clones,
      we could exclude ras p21 oncoprotein expression as the causal mechanism for
      repair deficiency, since both clone types expressed similar levels of the mutated
      protein and only the malignant tumorigenic cells showed repair deficiency. The
      results suggest that mutated p21 ras provided the human keratinocytes with a
      growth advantage in vivo (benign tumor growth), but acquisition of repair
      deficiency is required for progression from benign to malignant state.

PMID- 8293546
TI  - Sulfation of aromatic hydroxamic acids and hydroxylamines by multiple forms of
      human liver sulfotransferases.
AB  - Sulfation activity towards various heterocyclic and homocyclic aromatic
      hydroxamic acids and hydroxylamines was determined in adult human liver cytosol
      and with partially purified human liver sulfotransferases (STs). In adult human
      liver cytosols comparable ST activities towards N-hydroxy-2-acetyl-amino-5
      phenylpyridine (N-OH-2AAPP), N-hydroxy-4-acetylaminobiphenyl (N-OH-4AABP) and N
      hydroxy-4'fluoro-4-acetylaminobiphenyl (N-OH-4FAABP) were found, while the
      sulfation rates towards N-hydroxy-2-acetylaminofluorene (N-OH-2AAF), N-hydroxy-2
      acetylaminonaphthalene (N-OH-2AAN), N-hydroxy-2-acetylaminophenanthrene (N-OH
      2AAP) and N-hydroxy-4-acetylaminostilbene (N-OH-4AAS) were two- to five-fold
      lower. In adult liver cytosol ST activity was found towards all hydroxylamines
      tested. No significant differences were found for the various hydroxylamines. In
      general, the ST activities towards the various hydroxamic acids and
      hydroxylamines were comparable to phenol ST activity using adult liver cytosols.
      Partial purification of adult human liver STs was achieved by DEAE-Sepharose
      chromatography followed by anion exchange FPLC. Two separated protein peaks
      showing both N-OH-2AAPP and N-OH-2APP ST activities were observed and were
      designated human hydroxylamine/hydroxamic acid sulfotransferase (hHST) 1 and 2.
      Immunoblot analysis using an anti-rat estrogen ST antibody demonstrated cross
      reactivity with both hHSTs at a subunit mol. wt of 32 kDa corresponding to the
      phenol-sulfating form of phenol ST (P-PST). ST activity towards dopamine was low
      with both hHSTs, but hHST1 also contained significant capacity to sulfate
      dehydroepiandrosterone. The highest ST activity towards N-OH-2AAPP and N-OH-2APP
      was measured at pH 5.5 with both hHSTs. The Km values of the two hHSTs for
      sulfation of N-OH-2AAPP and N-OH-2APP were comparable, while the Vmax values for
      sulfation of N-OH-2APP were higher than for N-OH-2AAP with both hHSTs. FPLC anion
      exchange analysis of human platelet STs demonstrated that sulfation of N-OH-4ABP
      and N-OH-4AABP was associated with P-PST rather than M-PST (platelets do not
      possess any significant DHEA ST activity). Our results show that the various
      hydroxamic acids and hydroxylamines are converted by at least two hHSTs. The
      results presented here for the human liver hydroxamic acid and hydroxylamine ST
      activities are discussed in relation to those observed in the rat.

PMID- 8293547
TI  - Synergistic interaction between the non-phorbol ester-type promoter mirex and 12
      O-tetradecanoylphorbol-13-acetate in mouse skin tumor promotion.
AB  - Mirex, an organochlorine pesticide and non-genotoxic rodent hepatocarcinogen, is
      also a potent non-phorbol ester-type promoter of mouse skin tumors. Mirex, unlike
      most other skin tumor promoters, is not a significant epidermal hyperplasiogen
      even at a maximally promoting dose (200 nmol). Experiments described here
      examined whether tumor promotion by mirex and 12-O-tetradecanoylphorbol-13
      acetate (TPA) are mediated through different mechanisms as indicated by their
      additivity when co-applied to 7,12-dimethyl-benz[a]anthracene (DMBA, 200 nmol)
      initiated female CD-1 mouse skin. Instead of the additive response of 14 plus 5
      tumors/mouse predicted from mice promoted for 20 weeks (2x/week) with either
      mirex (200 nmol) or TPA (2 nmol) respectively, their co-application yielded 35
      tumors/mouse. This synergy with TPA was specific to mirex since a structurally
      related compound, chlordecone (Kepone) was inactive. Mirex plus TPA-promoted
      papillomas contained a c-Ha-ras A182-->T mutation as frequently (13/14) as those
      promoted by mirex or TPA alone, suggesting that these DMBA-initiated/co-promoted
      papillomas were not atypical in this genotypic marker. Promotional synergy with
      mirex was only observed with a submaximal promoting dose of 2 nmol TPA; 5 or 8
      nmol TPA plus mirex gave additive or less tumor multiplicities. This synergistic
      multiplicity with mirex plus 2 nmol TPA (35 tumors/mouse) approximated the sum of
      individual responses to 200 nmol mirex (14 tumors/mouse) and the maximally
      promoting dose of TPA (12 nmol), 24 tumors/mouse, suggesting that mirex
      potentiated the promotional activity of TPA, as well as promoted through a mirex
      specific mechanism. Epidermal DNA synthesis induced by 2 nmol TPA was potentiated
      by mirex, further supporting a role for mirex in potentiation of epidermal TPA
      activity. Collectively, these studies suggest that mirex affects two possibly
      related responses: (i) promotion through a distinct mirex-specific mechanism, and
      (ii) potentiation of a mechanism mediating the promotional activity of TPA.

PMID- 8293548
TI  - Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human
      lymphoblastoid cells containing human cytochrome P450s.
AB  - The clastogenicity of tamoxifen and toremifene was tested in six human
      lymphoblastoid cell lines each expressing increased monooxygenase activity
      associated with a specific transfected human cytochrome P450 cDNA (CYP1A1,
      CYP1A2, CYP2D6, CYP2E1 or CYP3A4). The chemicals were also tested in a cell line
      (MCL-5) expressing elevated native CYP1A1 and containing transfected CYP1A2,
      CYP2A6, CYP2E1 and CYP3A4 and epoxide hydrolase, and in a cell line containing
      only the viral vector (Ho1). Dose-related increases in micronuclei were observed
      when cells expressing 2E1, 3A4, 2D6 or MCL-5 cells were exposed to tamoxifen. The
      positive responses in the cell lines were in the order MCL-5 > 2E1 > 3A4 > 2D6.
      Toremifene also gave positive results with 2E1, 3A4 and MCL-5 cells, although the
      responses were less marked and the positive effects required higher doses than
      with tamoxifen. A synthesized epoxide of tamoxifen was also tested in these cell
      lines and produced similar increases in the incidences of micronucleated cells.
      The increases in the responses observed with the epoxide were greater than with
      tamoxifen or toremifene. The P450 isoenzyme activities in these cells were in a
      range similar to those of human tumour-derived cell lines. Microsomes (1A1, 2A2,
      2A6, 2B6, 2E1, 3A4 and 2D6) from these cells all metabolized tamoxifen. The major
      metabolite detected by HPLC was N-desmethyltamoxifen, and 4-hydroxytamoxifen was
      also detected in cells with cytochrome P450 2E1 and 2D6. These results are
      consistent with the following conclusions. (1) Tamoxifen requires metabolic
      activation to DNA-reactive species by specific CYP monooxygenases in order to
      exert its genotoxic effects. (2) The positive clastogenic effects elicited in
      lymphoblastoid cells by tamoxifen epoxide suggest that the genotoxic (and
      possibly the carcinogenic) effects of tamoxifen may be due to one or more epoxide
      metabolites that are generated intracellularly, probably in close proximity to
      the nucleus. (3) Tamoxifen is more genotoxic than toremifene.

PMID- 8293549
TI  - Flow cytometric investigation of a possible precursor--product relationship
      between oval cells and parenchymal cells in the rat liver.
AB  - The question of a possible precursor--product relationship between oval cells and
      hepatocytes was examined in rats treated for 2 weeks with 2-acetylaminofluorene
      (2-AAF) with a two-thirds partial hepatectomy (PH) performed after the first week
      of 2-AAF treatment (modified Solt-Farber model). Liver cells were pulse-chase
      labelled with bromodeoxyuridine (BrdU) on day 6 post PH. On day 7 post PH the
      nonparenchymal (NPC) fraction, which contains the oval cells, exhibited a
      labelling index (LI) approximately 10 times higher than that of the hepatocytes
      as analysed by flow cytometry (FCM), the majority of the proliferating cells
      being oval cells. At later time points, there was no significant increase in the
      LI of diploid hepatocytes, and no detectable shift of BrdU-labelled cells from
      the NPC fraction to the hepatocyte fraction, suggesting that no extensive
      conversion of BrdU-labelled oval cells to hepatocytes was taking place.
      Throughout the experimental period there was a significant increase in the
      diploid hepatocyte cell fraction, from 12% on day 7 to 25% on day 13 post PH.
      Diploid hepatocytes pulse-labelled on days 7 or 9 post PH had a high LI (7-8%),
      in contrast to the low LI (1%) of tetra- and octoploid cells. Proliferation of
      diploid hepatocytes may thus explain the large increase in the diploid hepatocyte
      fraction observed from days 9 through 15 post PH. Our results, therefore, provide
      no reason to invoke oval cells as precursors of hepatocytes in the modified Solt
      Farber carcinogenesis model.

PMID- 8293550
TI  - Heme oxygenase expression in Swiss 3T3 cells following exposure to aqueous
      cigarette smoke fractions.
AB  - A dose-dependent and transiently elevated expression of a cytoplasmic 32 kDa
      protein was observed in Swiss albino 3T3 fibroblasts exposed to mainstream
      cigarette smoke (CS) trapped in phosphate-buffered saline solutions (smoke
      bubbled PBS). The protein was identified as heme oxygenase (HO) (heme, hydrogen
      donor:oxygen oxidoreductase, EC 1.14.99.3) by Western blotting using an anti
      rodent HO-specific antibody. Kinetic investigations revealed that HO protein and
      its mRNA were detectable in smoke-bubbled PBS-treated cells between 1 and 24 h
      after exposure to 0.03 puffs (approximately 1 cm3) CS per ml medium. As a result
      of transcriptional activation, a nearly 50-fold increase in the amount of HO mRNA
      was determined after 8 h exposure compared to control levels. Since literature
      data indicate that there is a link between glutathione depletion and HO
      expression, the same was assumed for cells exposed to smoke-bubbled PBS, as a
      decrease of more than 60% in glutathione levels was observed after the exposure.
      This was further supported by the observation that no elevated amounts of HO mRNA
      appeared in smoke-bubbled PBS-treated cells when cysteine was exogenously added.
      However, although these effects may be attributable to the formation of hydroxyl
      radicals (which have been shown to induce HO and to deplete glutathione levels
      and which appear in aqueous smoke-containing solutions via the iron-catalysed
      Fenton reaction) neither catalase nor the iron cation chelating agent o
      phenanthroline were able to suppress or even to reduce HO expression in smoke
      bubbled PBS-treated cells. On the contrary, at comparable concentrations both
      compounds were found to be potent inhibitors of smoke-dependent DNA strand
      breaks. Hence, reactive species other than Fenton reaction-derived hydroxyl
      radicals are responsible for the effects observed in the present study.

PMID- 8293552
TI  - Salmonella typhimurium strain TA100 differentiates several classes of carcinogens
      and mutagens by base substitution specificity.
AB  - The mutational specificity of N-methylnitrosourea (MNU), nitrosoguanidine (MNNG),
      methyl methanesulfonate (MMS), sodium azide (NaN3), 4-nitroquinoline oxide
      (4NQO), benzo[a]pyrene (BP), nitrofurantoin (NF), aflatoxin B1 (AFB1), adriamycin
      (ADM) and UVA-activated angelicin in Salmonella typhimurium strain TA100 has been
      examined using allele-specific oligonucleotide hybridization and DNA sequence
      analyses. These ten mutagens produced five unique classes of reversion spectra,
      distinct from spontaneous, or the previously characterized 5-azacytidine,
      ultraviolet light (UV), 8-methoxypsoralen plus UVA (PUVA) and 60Co-induced
      mutation spectra. For example, 90% of MNU and MNNG-induced mutations in strain
      TA100 revertants were G:C-->A:T transitions with the majority (82%) occurring in
      the first position of the CCC codon. In contrast, NaN3 preferentially induced G:C
      ->A:T transitions at the second codon position (78%). Although MMS, NQO, BP, NF,
      ADM and AFB1 induced primarily G:C-->T:A transversions (73-86%), these mutagens
      fall into two classes based on site preference: NF and AFB1 yielded almost
      exclusively position two transversions (69-78%) whereas ADM, NQO, BP and MMS
      exhibited a two-fold preference for site 2 over site 1 (on average 52% versus
      22%). Angelicin photomutagenesis resulted in the recovery of G:C-->A:T and G:C-
      >T:A mutations at both codon positions in roughly equal proportions
      (approximately 20-25% each). Approximately 1% of the mutagen-induced revertants
      occurred via extragenic tRNA suppressor mutations, while 1% were multiple
      (usually tandem double) base substitutions. Ultraviolet mutagenesis experiments
      demonstrated that tandem base substitutions are promoted by pKM101-encoded mucAB
      gene products. A comparison of the mutagenic specificity derived for several
      carcinogens in hisG46 with the responses of several eukaryotic gene targets (e.g.
      HPRT, aprt, supF) revealed a high concordance between these targets. Thus, the
      Salmonella hisG46 locus provides a rapid, simple system for determining base
      substitution specificity and for studying mechanisms of mutagenesis.

PMID- 8293551
TI  - Induction of cyp2e-1 protein in mouse colon.
AB  - The inducibility of a cytochrome P450 isoform, CYP2E1 (cyp2e-1), was compared in
      colonic epithelium of selected inbred mice. Mice were chosen for study on the
      basis of reported susceptibility to 1,2-dimethylhydrazine (DMH)-induced
      colorectal tumor formation. DBA/2J (resistant), C57BL/6J (intermediate) and SWR/J
      (susceptible) mice were exposed to acetone (1% v/v) in drinking water for 10
      days. SWR/J mice sustained the largest increase in colonic cyp2e-1, although
      protein levels, assessed by Western analysis, were markedly increased in mucosal
      tissue obtained from C57BL/6J mice as well. Further evidence for colonic cyp2e-1
      induction is supported by elevated (3.5-fold) chlorzoxazone 6-hydroxylase
      activity in response to acetone. To more fully characterize these changes in
      colon, the tumor-sensitive SWR/J mice were chosen for further evaluation. Mice
      were treated with a panel of agents established to induce this protein in liver,
      including isoniazid (0.1% v/v) and ethanol (10% v/v) in drinking water and
      pyrazole (300 mg/kg), given intraperitoneally. With the exception of ethanol,
      each compound produced a marked (1.5- to 3-fold) elevation of cyp2e-1 in colon
      and liver. Overall balance between phase I and II metabolism may be a critical
      factor in determining tumor susceptibility. Therefore, glutathione S-transferase
      (GST) activity was also examined. In liver, basal GST levels varied less than 2
      fold between strains, while in colon, levels were 5-10% of corresponding hepatic
      levels. Although acetone treatment did not significantly alter hepatic GST, a 30
      60% decline in activity was observed in colons of SWR/J and C57BL/6J mice.
      Further examination of colonic GST revealed compound-specific effects. Ethanol
      exposure markedly (60%) lowered GST levels in colon, whereas pyrazole produced a
      2-fold increase. None of these agents significantly altered hepatic GST activity.
      These studies demonstrate the ability of mouse colon to undergo an increase in
      immunoreactive cyp2e-1 in response to a panel of xenobiotics known to elevate
      this protein in liver. Further characterization of cyp2e-1 and GSTs in inbred
      mice may provide important information on the role of colonocytes in direct
      activation of ingested procarcinogens to DNA-reactive metabolites.

PMID- 8293553
TI  - Characterization and evaluation by 32P-postlabelling of psoralen-type DNA adducts
      in HeLa cells.
AB  - Samples of DNA irradiated at 405 and/or 365 nm in the presence of 8
      methoxypsoralen (8-MOP) were analysed via a modified postlabelling assay using
      three hydrolysis enzymes other than those employed previously. These enzymes
      (deoxyribonucleaseI, venom phosphodiesterase and alkaline phosphatase) liberated
      3'-adducted dinucleotide monophosphate instead of the 5'-modified dinucleotide
      monophosphate normally obtained. The first separation chromatography (D1) of
      samples irradiated in the presence of 8-MOP showed a single spot above the
      origin, and the next separation (D2) resolved this spot into two components
      (spots I and II). Double irradiation experiments in which samples of DNA were
      first irradiated at 405 nm before being irradiated at 365 nm showed that spot II
      could be transformed into spot I. The use of 6,4,4'-trimethylangelicin, which
      induced only photomonoadducts under UVA irradiation, gave only spot II. These two
      results indicated that spots I and II were respectively due to interstrand cross
      links and monoadducts. Dose-effect experiments showed that spots I and II were
      dose dependent, and low-dose irradiations permitted us to measure one interstrand
      cross-link and two monoadducts per 10(8) base pairs.

PMID- 8293554
TI  - Alterations of nuclear pores in preneoplastic and neoplastic rat liver lesions
      induced by 2-acetylaminofluorene.
AB  - The nuclear pore density and area were measured on freeze-fractured nuclei of
      ACI/N rat liver altered foci, adenomas and carcinomas induced by 2
      acetylaminofluorene, and compared with those of normal hepatocytes. The pore
      density of nuclei from these preneoplastic and neoplastic lesions was
      significantly higher than that of hepatocytes, but there was no difference
      between lesions. The area of nuclear pores of the focus cells did not differ from
      normal hepatocytes, whereas the areas of pores of adenoma and carcinoma cells
      were increased. Moreover, the nuclear pore area of carcinomas was significantly
      greater than that of adenomas. These results suggest that some changes may occur
      in nuclear pores in the progress of tumorigenesis.

PMID- 8293555
TI  - Cell cycle dependent sensitivity of human melanoma cells to melphalan is
      correlated with the activity and cellular concentration of glutathione
      transferases.
AB  - Glutathione transferases (GSTs) are enzymes involved in the resistance of tumor
      cells to bifunctional alkylating cytostatic drugs. We investigated the melphalan
      sensitivity together with activity and cellular concentration of GST isoenzymes
      of human melanoma cell line RPMI 8322 in different phases of the cell cycle. By
      centrifugal elutriation three cell fractions containing different proportions of
      cells in the G1 phase were isolated. Melphalan sensitivity was estimated by the
      colony formation assay. The cell fraction with the largest proportion of G1 cells
      was more sensitive to the drug than the fractions enriched in S and G2 cells. The
      GST activity of the cell fractions was measured with 1-chloro-2,4-dinitrobenzene
      (CDNB) as substrate and the concentrations of GST P1-1, GST M1-1 and GST A1-1
      were quantitated by use of isoenzyme-specific ELISA. The results show that there
      were less GST activity and lower GST P1-1 and A1-1 concentrations in the G1 cell
      enriched fraction, demonstrating a cell cycle dependence of GST expression. Thus,
      the cell fraction most sensitive to melphalan had the highest proportion of G1
      cells and displayed the lowest GST activity, suggesting that the cell cycle
      dependent sensitivity to melphalan may at least partially depend on the
      expression of GSTs.

PMID- 8293556
TI  - 3-Hydroxy-3-methyl glutaryl coenzyme A reductase inhibition modulates vasopressin
      stimulated Ca2+ responses in rat A10 vascular smooth muscle cells.
AB  - Previous evidence has indicated a role for changes in cell membrane cholesterol
      in the modulation of [Ca2+]i responses and smooth muscle contraction to vascular
      agonists. However, the actions of plasma cholesterol-lowering agents such as 3
      hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors (eg, simvastatin) have
      not been defined. Such agents may in addition affect isoprenoid intermediates
      that may play a role in signal transduction pathways involving G proteins.
      Arginine vasopressin-induced [Ca2+]i responses in A10 rat vascular myocytes were
      therefore studied in vitro. Vasopressin stimulated an initial peak [Ca2+]i that
      was independent of extracellular Ca2+ entry and a subsequent plateau that was
      dependent on Ca2+ influx, mainly through receptor-operated dihydropyridine
      insensitive divalent cation channels. Simvastatin-treated A10 cells (5 mg/L for
      24 hours) showed a normal initial peak response to vasopressin, but the plateau
      phase of Ca2+ entry was significantly impaired. By use of Mn2+ quenching of
      intracellular fura 2 to measure divalent cation entry, the maximal rate of
      vasopressin-stimulated Mn2+ entry was impaired in simvastatin-treated cells by
      52%. Mevalonate (1 mmol/L for 4 hours at 37 degrees C) reversed all the changes
      in simvastatin-treated cells. There were no associated changes in total cellular
      cholesterol or fluorescence anisotropy measurements with simvastatin treatment.
      Measurements of inositol-1,4,5-trisphosphate mass showed that simvastatin did not
      impair the initial peak response to vasopressin but significantly reduced the
      subsequent plateau phase. These changes were also reversed with mevalonate
      incubation. These findings suggest that simvastatin has additional effects on
      [Ca2+]i homeostasis that are independent of changes in total cell cholesterol.

PMID- 8293557
TI  - Viral infection and the pathogenesis of dilated cardiomyopathy.
AB  - Long-term follow-up studies of patients with suspected viral myocarditis reveal
      progression to dilated cardiomyopathy (DCM) in a significant number of cases.
      Thus, an underlying viral etiology has been hypothesized in the pathogenesis of
      ongoing heart disease that leads to DCM. Recent application of molecular biology
      in clinical diagnosis has strengthened this hypothesis. By use of probe
      hybridization and polymerase chain reaction, enteroviral RNA has been detected in
      the myocardium of patients at all stages of the disease process: myocarditis,
      chronic heart disease, and DCM. Experimental murine models of enterovirus-induced
      heart disease provide a framework for examining the pathogenic mechanisms. Viral
      cytotoxicity, immunological responses, viral RNA persistence, and spasm of the
      coronary microvasculature are all implicated in the ongoing disease process.
      Abnormal cardiac function and heart failure are attributed to the pathological
      changes that occur.

PMID- 8293558
TI  - Developmentally timed expression of an embryonic growth phenotype in vascular
      smooth muscle cells.
AB  - Little is known about the phenotypic changes that occur in vascular smooth muscle
      cells (SMCs) as the developing aorta undergoes the transition from a loosely
      organized, highly replicative tissue to a morphologically mature, quiescent
      tissue. In the present study, we have characterized the in vivo pattern of SMC
      replication during intrauterine and neonatal aortic development in the rat and
      have cultured and assessed the in vitro growth properties of embryonic, fetal,
      and neonatal vascular SMCs. Embryonic SMCs, which exhibited a very high in vivo
      replication rate (75% to 80% per day), demonstrated a significant potential for
      self-driven replication, as assessed by the ability to proliferate under serum
      deprived conditions. Several lines of evidence suggest that the autonomous growth
      of SMCs in the "embryonic growth phenotype" may be driven by a unique mechanism
      independent of known adult SMC mitogens: embryonic SMC replication was not
      associated with the detectable secretion of mitogenic activity capable of
      stimulating adult SMCs, and embryonic SMCs were mitogenically unresponsive to a
      variety of known adult SMC growth factors. The capacity for self-driven growth
      was lost by embryonic day 20, suggesting that important changes in gene
      expression and phenotype occur in developing SMCs between embryonic days 18 and
      20. Taken together, the data describe a unique embryonic growth phenotype of
      vascular SMCs and suggest that the replication of aortic SMCs during intrauterine
      development is self driven, self regulated, and controlled by a developmental
      timing mechanism. The conversion of SMCs from the embryonic to the late
      fetal/adult growth phenotype will likely be found to be an important component of
      a developmental system controlling vascular morphogenesis.

PMID- 8293559
TI  - Expression of prostaglandin H2-mediated mechanism of vascular contraction in
      hypertensive rats. Relation to lipoxygenase and prostacyclin synthase activities.
AB  - We tested the hypothesis that a prostanoid-mediated mechanism of vascular
      contraction is expressed in rats with aortic coarctation-induced hypertension.
      Rings of descending thoracic aorta taken from normotensive and hypertensive rats
      were contrasted in terms of constrictor responsiveness to arachidonic acid (AA),
      AA-induced release of eicosanoids, and ability to convert exogenous prostaglandin
      (PG) H2 to PGI2. AA (10(-8) to 10(-5) mol/L) increased isometric tension in
      aortic rings (bathed in Krebs' bicarbonate buffer) of hypertensive but not
      normotensive rats. AA (10(-5) mol/L) also elicited the release of PGI2, PGE2,
      thromboxane (TX) A2, and monohydroxyeicosatetraenoic acids (HETEs); this release
      from the aortic rings of hypertensive rats exceeded the corresponding release
      from the aortic rings of normotensive rats. However, the rate of conversion of
      exogenous PGH2 to PGI2 by aortic rings of hypertensive rats was < 50% the rate of
      conversion by aortic rings of normotensive rats. The constrictor effect of AA in
      aortic rings of hypertensive rats was abolished by an inhibitor of cyclooxygenase
      (indomethacin, 10 mumol/L) and a blocker of TXA2-PGH2 receptors (SQ29548, 1
      mumol/L) but was not affected by an inhibitor of TXA2 synthesis (CGS13080, 10
      mumol/L), suggesting mediation by PGH2. The lipoxygenase inhibitor baicalein (75
      mumol/L) also attenuated the constrictor effect of AA in aortic rings of
      hypertensive rats while decreasing the associated release of HETEs and correcting
      the impairment in the conversion of PGH2 to PGI2.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8293560
TI  - Expression of beta-arrestins and beta-adrenergic receptor kinases in the failing
      human heart.
AB  - The beta-adrenergic receptor system of the failing human heart is markedly
      desensitized. We have recently postulated that this desensitization may in part
      be caused by an increase in beta-adrenergic receptor kinase (beta ARK)
      expression. beta ARK is thought to effect desensitization by acting in concert
      with an inhibitor protein, called beta-arrestin. Two isoforms have been
      identified both for beta ARK and for beta-arrestin. In the present study, we have
      investigated the expression of the individual isoforms of beta-arrestin and of
      beta ARK in left ventricles from failing and control human hearts. mRNAs for all
      four proteins, beta-arrestin-1, beta-arrestin-2, beta ARK-1, and beta ARK-2, were
      identified in human heart. Quantitation by reverse-transcription polymerase chain
      reactions showed that in heart failure there were no changes of the mRNA levels
      for beta-arrestin-1 and beta-arrestin-2, a slight (< 50%) increase of the mRNA
      for beta ARK-2, and a threefold increase for beta ARK-1 mRNA. At the protein
      level, beta-arrestin-1 was readily detected by Western blotting in human heart.
      Its absolute values were approximately 350 fmol/mg cytosolic protein, and its
      expression was not changed in heart failure. beta-Arrestin-2 levels were too low
      to be detectable using the same methods. beta ARK levels as determined by
      enzymatic activity were approximately 20 fmol/mg cytosolic protein (beta ARK-1
      plus beta ARK-2) and thus almost 20-fold lower than those of beta-arrestin. beta
      ARK levels were increased approximately twofold in heart failure.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8293561
TI  - Osteopontin promotes vascular cell adhesion and spreading and is chemotactic for
      smooth muscle cells in vitro.
AB  - Osteopontin is an Arg-Gly-Asp-containing acidic phosphoprotein recently shown to
      be upregulated in vascular smooth muscle during rat arterial neointima formation
      and in human atherosclerotic plaques. Functional studies showed that osteopontin
      promoted adhesion of both cultured aortic endothelial cells and aortic smooth
      muscle cells. Adhesion of vascular cells to osteopontin was dose dependent and
      half maximal when solutions containing 7 and 30 nmol/L osteopontin were used to
      coat wells for endothelial and smooth muscle cells, respectively. Smooth muscle
      cells adherent to osteopontin were spread after 60 minutes, whereas endothelial
      cells remained round, although flattened, at this time point but were spread at
      90 minutes. Cell spreading on osteopontin was accompanied by the formation of
      focal adhesion plaques. A newly developed anti-osteopontin antibody completely
      inhibited adhesion of both cell types to osteopontin but not to fibronectin or
      vitronectin. In addition, the peptide GRGDSP blocked adhesion to osteopontin,
      suggesting that integrins mediate Arg-Gly-Asp-dependent adhesion. Indeed, an
      antibody against the alpha v beta 3 integrin neutralized adhesion of both
      endothelium and smooth muscle cells to osteopontin by approximately 50%,
      demonstrating that alpha v beta 3 is one osteopontin receptor on vascular cells.
      Osteopontin also promoted the migration of smooth muscle cells in a Boyden-type
      chamber, with half-maximal effects observed at 77 nmol/L osteopontin.
      Checkerboard analysis demonstrated that this stimulus was chemotactic in nature.
      Our findings suggest that osteopontin may be functionally important as an
      adhesive and chemotactic molecule for vascular cells, particularly when levels of
      osteopontin are dramatically increased, as is the case after arterial angioplasty
      and in atherosclerotic plaques.

PMID- 8293562
TI  - Peripheral adaptations in trained aged rats with femoral artery stenosis.
AB  - The development and functional significance of exercise-induced peripheral
      adaptations were evaluated in aged animals with peripheral arterial
      insufficiency. Fisher 344 male rats (21 months old) were subjected to bilateral
      stenosis of the femoral arteries sufficient to limit active hyperemia but not to
      impair resting blood flow. Beginning the third day after stenosis, animals were
      (1) exercised by walking (n = 12) on a treadmill at 20 m/min at 15% inclination,
      twice a day, 5 days per week, or (2) limited to cage activity (n = 10). Exercise
      tolerance improved from approximately 5 to approximately 35 minutes (P < .001)
      over the 8 weeks of the training program but increased only marginally to
      approximately 8 minutes for the sedentary group. An isolated hind limb
      preparation perfused at equivalent blood flows (approximately 1 ml.min-1 x g-1
      with an arterial blood oxygen content of approximately 20 vol%) was used to
      assess the functional and metabolic impact of muscle-specific adaptations during
      sequential contraction periods at 4, 8, 15, 30, 45, 60, 75, and 90 tetani per
      minute. An initially similar force development of approximately 10 N/g was better
      maintained (P < .001) by the trained group. The peak oxygen consumption attained
      by the trained group of 5.68 +/- 0.34 mumol.min-1 x g-1 was greater (P < .01)
      than that of the sedentary group (4.34 +/- 0.29 mumol.min-1 x g-1). This was due
      to a greater oxygen extraction, since oxygen delivery was the same (approximately
      10 mumol.min-1 x g-1) to muscles of both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293563
TI  - Hyaluronate degradation affects ventricular function of the early postlooped
      embryonic rat heart in situ.
AB  - Hyaluronic acid is the major glycosaminoglycan of the early cardiac extracellular
      matrix or "cardiac jelly," yet little is known about its role in the ontogeny of
      early ventricular performance. To investigate the in situ effect of hyaluronate
      degradation on ventricular function, whole rat embryos were cultured in rat serum
      alone (control embryos) or rat serum plus 20 TRU/mL of Streptomyces hyaluronidase
      (treatment embryos) from gestational day 9.5 (before formation of the heart tube)
      through initial looping of the heart. Cardiac function was measured before
      looping (24 hours in culture) and immediately after looping (36 hours in culture)
      by video motion analysis of the external wall motion of the bulbus cordis and
      primitive ventricle. Degradation of hyaluronic acid in the treated embryos was
      confirmed by Alcian blue staining at pH 2.5. Significant increases in heart rate,
      circumferential shortening fraction, maximum velocity of circumferential
      contraction, and maximum velocity of circumferential relaxation were observed
      with looping in both control and treatment embryos. Although there was minimal
      difference in ventricular performance between control and treatment embryos
      before looping, there was a significant increase in all parameters of ventricular
      performance in the hyaluronidase-treated embryos immediately after looping of the
      heart. Endocardial cushions were absent in hyaluronidase-treated embryos, and an
      additional group of embryos cultured in the presence of Streptomyces
      hyaluronidase for 48 to 72 hours failed to develop endocardial cushions. These
      experiments are the first to (1) document a quantifiable increase in ventricular
      performance during early cardiac looping and (2) demonstrate that hyaluronate
      degradation results in abnormal endocardial cushion formation and altered
      ventricular performance of the postlooped heart.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293564
TI  - Enhanced Na(+)-Ca2+ exchange activity in cardiomyopathic Syrian hamster.
AB  - The signaling of contraction by Ca2+ in the Syrian hamster (BIO 14.6) heart in
      the late stage of the cardiomyopathy (220 to 300 days old) was compared with that
      in age-matched healthy hamster hearts. Membrane current and cell shortening or
      intracellular Ca2+ transients were measured simultaneously in isolated whole-cell
      clamped myocytes. The density of the L-type Ca2+ current was smaller in myopathic
      than in normal myocytes (2.13 +/- 0.3 versus 3.21 +/- 0.4 pA/pF at 0 mV, P <
      .05). In both control and myopathic myocytes, the L-type Ca2+ current gated the
      release of Ca2+ and activation of contraction. In myopathic myocytes, activation
      of contraction also activated a slowly inactivating inward current of 1.73 +/-
      0.2 pA/pF. The Na(+)-Ca2+ exchanger generated this current (INa-Ca), because it
      was suppressed by rapid replacement of Na+ with Li+ and depletion of the
      intracellular Ca2+ pool by caffeine. INa-Ca, activated by rapid application of
      caffeine, was not significantly different in both groups (3.7 +/- 0.5 pA/pF in
      control hearts versus 3.9 +/- 0.5 pA/pF in cardiomyopathic hearts). The
      activation of the inward exchanger current in myopathic myocytes coincided with a
      significant prolongation of contraction and the intracellular Ca2+ transient and
      a delay in the onset of relaxation. These results suggest that the enhanced
      activity of the Na(+)-Ca2+ exchanger may be related to compromised sequestration
      of Ca2+ in these animals.

PMID- 8293565
TI  - Ventricular mechanoreflex and chemoreflex alterations in chronic heart failure.
AB  - Cardiac and arterial baroreflex control of the circulation is abnormal in both
      human and experimental heart failure. Ventricular vagal afferents mediate
      mechanical and chemical reflexes, which result in bradycardia and hypotension.
      The aim of the present study was to evaluate the changes that occur in
      ventricular mechanoreflexes and chemoreflexes in a conscious canine model of
      chronic heart failure. Dogs were instrumented for the measurement of left
      ventricular pressure, left atrial pressure, arterial pressure, and heart rate.
      Vascular occluders were placed on the ascending thoracic aorta, on the descending
      thoracic aorta, and on the thoracic inferior vena cava. A chronic left circumflex
      coronary artery catheter was also implanted. Finally, a pacing lead was secured
      to the left ventricular free wall. After recovery from surgery (10 to 14 days),
      the dogs were subjected to complete arterial baroreceptor denervation. The
      responses to vascular occlusions and intracoronary administration of prostacyclin
      (PGI2) were carried out before and after heart failure was induced by chronic
      cardiac pacing at 250 beats per minute. PGI2 was used as a chemical stimulus for
      ventricular afferents; ascending aortic occlusion was used as a mechanical
      stimulus. Before chronic pacing, ascending aortic occlusion resulted in a
      decrease in heart rate of 36.1 +/- 12.3 beats per minute (mean +/- SD, P < .001).
      After heart failure was induced, the heart rate response to ascending aortic
      occlusion was almost completely abolished. The slope of the linear relation
      between pulse interval and left ventricular end-diastolic pressure was reduced by
      90.5% from a control value of 11.3 +/- 6.9 ms/mm Hg after heart failure had been
      induced.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293566
TI  - Effect of ischemia and reperfusion on cardiac ryanodine receptors--sarcoplasmic
      reticulum Ca2+ channels.
AB  - We investigated the effect of ischemia and reperfusion on the cardiac ryanodine
      receptor, which corresponds to the sarcoplasmic reticulum Ca2+ channel. Isolated
      working rat hearts were subjected to 10 to 30 minutes of global ischemia,
      followed or not by reperfusion. Ischemia produced significant reduction in the
      density of high-affinity 3H-ryanodine binding sites, determined either in whole
      heart homogenate (Bmax, 220 +/- 22, 203 +/- 12, and 228 +/- 14 fmol/mg protein
      after 10, 20, and 30 minutes of ischemia versus 298 +/- 18 fmol/mg protein in the
      control condition; P < .01) or in a fraction enriched in sarcoplasmic reticulum
      (Bmax, 1.08 +/- 0.15 pmol/mg protein after 20 minutes of ischemia versus 1.69 +/-
      0.08 pmol/mg protein in the control condition; P < .01). The Kd (1.5 +/- 0.1
      nmol/L) and the Ca2+ dependence of high-affinity 3H-ryanodine binding were not
      affected by ischemia. The density of low-affinity 3H-ryanodine binding sites was
      also reduced after 20 minutes of ischemia (14.0 +/- 2.3 versus 34.0 +/- 8.2
      pmol/mg protein in the sarcoplasmic reticulum fraction, P < .05), without
      significant changes in Kd (4.7 +/- 1.2 versus 2.4 +/- 1.0 mumol/L). All these
      changes persisted after 20 minutes of reperfusion. Analysis of tissue fractions
      showed that 55% of the ryanodine binding sites were retained in the pellet of a
      low-speed centrifugation ("nuclear pellet") and that the effects of ischemia
      concerned only the receptors released in the supernatant ("postnuclear
      supernatant"). In parallel experiments, we evaluated the effect of ryanodine on
      oxalate-supported Ca2+ uptake, which represents sarcoplasmic reticulum Ca2+
      uptake. As expected, we found that high concentrations of ryanodine stimulated
      Ca2+ uptake, owing to channel blockade. The response to 900 mumol/L ryanodine was
      slightly reduced in crude homogenate and significantly reduced in postnuclear
      supernatant obtained from ischemic hearts. In conclusion, the number of ryanodine
      receptors is reduced after ischemia; this effect concerns a subpopulation of the
      receptors, persists after reperfusion, and might contribute to modify
      sarcoplasmic reticulum function.

PMID- 8293567
TI  - Cocaine-induced microvascular spasm in Yucatan miniature swine. In vivo and in
      vitro evidence of spasm.
AB  - The purpose of the present study was to determine the maximal coronary flow
      reserve (CFR) before and after the administration of successive cocaine doses
      (0.1, 0.5, 3, and 7 mg/kg IV) for 2 minutes at 10-minute intervals in eight
      miniature swine. CFR was assessed by the administration of adenosine (0.03, 0.3,
      and 3 mg IC). Hemodynamic and flow measurements were performed 3 minutes after
      each dose. Coronary flow (CF) was measured with a Doppler-tipped wire in the
      proximal left anterior descending coronary artery (LAD). Also, microvessels were
      dissected, and vessel diameters were measured by a videoelectronic dimension
      analyzer. In vivo, LAD CF increased fourfold, CFR increased twofold, and coronary
      vascular resistance (CVR) decreased fourfold after the administration of
      adenosine. In contrast, LAD CF decreased threefold, CFR decreased onefold, and
      CVR increased sixfold 3 minutes after the administration of cocaine. Adenosine (3
      mg) was repeated 4 minutes after the administration of cocaine, and LAD CF
      increased 1.4-fold, CVR increased 2.5-fold, and CFR decreased onefold. Thus,
      adenosine partially reversed the potent cocaine constrictor effect. In vitro, 10(
      9) mol/L cocaine decreased the diameter of the coronary microvessels from 129 +/-
      12 to 127 +/- 12 microns, and 10(-4) mol/L cocaine decreased coronary microvessel
      diameter to 114 +/- 15 microns (P < .05). In conclusion, cocaine in vivo
      decreases CFR, and consistent with the in vivo effect, cocaine in vitro produced
      constriction of vessels < 200 microns. These results indicate that cocaine can
      produce profound microvascular spasm. This may contribute to the
      ischemia/infarction reported in patients who abuse cocaine and who are
      subsequently found to have normal epicardial coronary arteries.

PMID- 8293568
TI  - Integrin-mediated collagen gel contraction by cardiac fibroblasts. Effects of
      angiotensin II.
AB  - Angiotensin II (Ang II), a vasoactive octapeptide, has been implicated in cardiac
      growth and the development of hypertrophy and fibrosis secondary in hypertensive
      disease. These consequences of Ang II imply an effect on the function and
      morphology of cardiac interstitial cells (fibroblasts). The present investigation
      was designed to (1) determine whether neonatal heart fibroblasts (NHFs) possess
      functional Ang II receptors on their plasma membrane and (2) examine the effects
      of Ang II on NHFs in vitro using three- and two-dimensional (3D and 2D,
      respectively) cultures. Several analytic techniques were used to test the
      specific questions of the present study. Since cardiac fibroblast phenotype can
      be influenced by culture conditions, both 2D and 3D cultures were used in the
      present investigations. Reverse-transcriptase polymerase chain reaction and
      radioligand binding analysis were used to test for the presence of Ang II
      receptors on NHFs. Both revealed that NHFs in 2D culture possess Ang II receptor
      mRNA and Ang II receptors. When isolated NHFs were cultured in 3D collagen gels
      and treated with Ang II, gel contraction was stimulated by NHFs. This effect was
      attenuated by the specific Ang II receptor antagonist [Sar1,Ala8]Ang II. Ang II
      stimulated gel contraction was completely inhibited by extracellular matrix
      receptor (beta 1-integrin) antibodies (P < .05), supporting previous studies
      indicating that collagen gel contraction is mediated via the integrins.
      Immunofluorescent staining was used to test the localization of cell-surface
      integrins. A more intense staining pattern for beta 1-integrin in Ang II-treated
      versus control cells was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293569
TI  - Protein kinase C isoform expression and regulation in the developing rat heart.
AB  - To determine whether age-dependent differences in cardiac responses to autonomic
      agonists could result from developmental changes in protein kinase C (PKC)
      isoform expression, we probed extracts from the fetal, neonatal, and adult heart
      as well as cultured neonatal and isolated adult ventricular myocytes with
      specific antisera to calcium-dependent (alpha and beta) and calcium-independent
      (delta, epsilon and zeta) isoforms of the enzyme. Although PKC-beta
      immunoreactivity could not be detected in cultured neonatal or isolated adult
      ventricular myocytes, adult and neonatal myocytes expressed multiple other
      isoforms of PKC. Our studies revealed an age-dependent decline in the
      immunoreactivity for three PKC isoforms. PKC-alpha was detected in extracts from
      the fetal and 2-day-old neonatal heart as well as cultured neonatal rat
      ventricular myocytes. Only faint PKC-alpha immunoreactivity was detected in
      extracts from the adult heart, and PKC-alpha was not detected in extracts from
      isolated adult ventricular myocytes, suggesting that PKC-alpha resides in
      nonmyocyte elements in the adult heart. PKC-delta also was detected in greater
      abundance in fetal and neonatal than in adult myocardial extracts. The decline in
      PKC-alpha and PKC-delta expression occurred during the first 2 postnatal weeks.
      PKC-zeta was detected in greatest abundance in extracts from the fetal heart. PKC
      zeta expression declined markedly by the second postnatal day, and only faint PKC
      zeta immunoreactivity was detected in extracts from adult myocardium. Failure to
      detect PKC-zeta in extracts from isolated adult ventricular myocytes suggests
      that PKC-zeta resides primarily in nonmyocyte elements in the adult heart. PKC
      epsilon was detected in all preparations, but it was detected in greatest
      abundance in extracts from neonatal hearts. In vitro sympathetic innervation of
      previously noninnervated neonatal ventricular myocytes or in vivo chemical
      sympathectomy of the neonatal heart did not modulate PKC isoform expression,
      suggesting that sympathetic innervation does not significantly regulate PKC
      isoform expression. PKC-alpha partitioned to the soluble fraction of unstimulated
      myocytes and was selectively translocated to the particulate fraction by Ca2+. In
      contrast, a major portion of the novel PKC isoforms partitioned to the
      particulate fraction of unstimulated myocytes. The subcellular distribution of
      novel PKC isoforms was not influenced by Ca2+. 12-O-Tetradecanoylphorbol 13
      acetate (TPA, 300 nmol/L) induced translocation of soluble PKC-alpha, PKC-delta,
      and PKC-epsilon to the particulate fraction at 30 minutes and complete (PKC-alpha
      and PKC-delta) or 80% (PKC-epsilon) downregulation at 24 hours. PKC-zeta was not
      affected by TPA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8293570
TI  - The mechanism of coronary collateral vasoconstriction in response to
      cyclooxygenase blockade.
AB  - The present study was performed to examine the mechanism by which cyclooxygenase
      blockade produces vasoconstriction in well-developed coronary collateral vessels.
      Eight dogs were studied 4 to 6 months after occlusion of the left anterior
      descending coronary artery (LAD) had been performed to stimulate collateral
      vessel growth. At the time of study, the LAD was cannulated at the site of
      occlusion for measurement of retrograde blood flow as an index of collateral
      blood flow. Levels of 6-ketoprostaglandin F1 alpha were 32 +/- 13% higher in
      blood diverted from the collateral-dependent LAD than in aortic blood (P < .05);
      the increase in this stable product of prostacyclin metabolism indicated
      production of prostacyclin across the coronary collateral system. Administration
      of arachidonic acid into the left main coronary artery to reach collateral
      vessels entering the LAD resulted in a 21 +/- 6% increase in retrograde flow (P <
      .01), demonstrating cyclooxygenase activity with production of vasodilator
      prostaglandins in the collateral system. Ibuprofen (10 mg/kg IV) caused a 55 +/-
      7% decrease in retrograde flow (P < .03), suggesting that cyclooxygenase blockade
      inhibited tonic production of vasodilator prostaglandins in the collateral
      system. In contrast, neither thromboxane synthase inhibition with dazmegrel nor
      thromboxane receptor blockade with SQ 30741 caused a significant change in
      collateral flow, thus failing to support thromboxane-induced collateral
      constriction. After cyclooxygenase blockade, prostacyclin infused into the left
      main coronary artery was able to restore retrograde flow to the preibuprofen
      level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293571
TI  - Interleukin-2-induced lung injury. The role of complement.
AB  - Pulmonary edema and sepsis-like syndrome are grave complications of interleukin-2
      (IL-2) therapy. Recent animal studies have suggested IL-2-induced microvascular
      injury as the underlying mechanism. Since complement factors have been shown to
      mediate increased vascular permeability in diverse conditions that lead to
      pulmonary injury and recombinant human IL-2 is known to activate the complement
      system in patients undergoing IL-2 therapy, we hypothesized that complement
      factors play a pivotal role in the development of increased vascular permeability
      after IL-2 treatment. To test this hypothesis, we evaluated the capacity of
      recombinant soluble human complement receptor type 1 (sCR1, BRL 55730), a new
      highly specific complement inhibitor, to attenuate IL-2-induced lung injury in
      the rat. Recombinant human IL-2 (intravenously for 60 minutes) at 10(6) U per rat
      (n = 4) elevated lung water content (37 +/- 6%, P < .05), myeloperoxidase
      activity (162 +/- 49%, P < .05), and serum thromboxane B2 (30 +/- 1 pg/100
      microL, P < .01) and had no effect on serum tumor necrosis factor-alpha sCR-1 at
      30 mg/kg (n = 5), but not at 10 mg/kg (n = 6), attenuated the elevation of lung
      water content (18 +/- 2%, P < .05) and myeloperoxidase activity (42 +/- 9%, P <
      .05) but failed to alter serum thromboxane B2 response to IL-2. These data
      suggest the involvement of complement in the pathogenesis of IL-2-induced
      pulmonary microvascular injury and point to the potential therapeutic capacity of
      complement inhibitors in combating this toxic effect of IL-2 therapy.

PMID- 8293572
TI  - Cardiac mitochondrial DNA polymerase-gamma is inhibited competitively and
      noncompetitively by phosphorylated zidovudine.
AB  - Zidovudine (azidothymidine [AZT]) inhibits human immunodeficiency virus
      replication and reduces the severity of acquired immunodeficiency syndrome. A
      limiting side effect of AZT is a mitochondrial cardiac and skeletal myopathy in
      which the pharmacologically active derivative of AZT (AZT triphosphate) plays a
      critical role. The present study determined biochemical mechanisms of AZT-induced
      mitochondrial toxicity and identified AZT triphosphate as an inhibitor of DNA
      polymerase-gamma in vitro. Inhibition kinetics were defined using purified bovine
      cardiac mitochondrial DNA polymerase-gamma and AZT triphosphate in vitro. The Km
      for deoxythymidine triphosphate was 0.8 +/- 0.3 mumol/L. AZT triphosphate
      incubation with DNA polymerase-gamma in vitro resulted in mixed kinetics with a
      competitive Ki of 1.8 +/- 0.2 mumol/L and a noncompetitive Ki' of 6.8 +/- 1.7
      mumol/L. These Ki and Ki' values were strikingly higher than values for
      retroviral reverse transcriptase but lower than values for other cellular DNA
      polymerases. These data support previous molecular and morphological findings in
      clinical AZT mitochondrial myopathy and in models of AZT myopathy in vivo.
      Biochemical findings suggest that inhibition of mitochondrial DNA polymerase
      gamma may be integral to the pathogenesis of AZT-induced myopathy.

PMID- 8293573
TI  - Steady-state mRNA levels of the sarcolemmal Na(+)-Ca2+ exchanger peak near birth
      in developing rabbit and rat hearts.
AB  - To functionally compensate for an underdeveloped sarcoplasmic reticulum in
      immature cardiomyocytes, it has been proposed that the sarcolemmal Na(+)-Ca2+
      exchanger may assume a more predominant role for regulating cytosolic Ca2+.
      Previous studies using sarcolemma prepared from developing rabbit hearts
      demonstrated that Na(+)-dependent Ca2+ uptake and exchanger protein content were
      highest at birth and declined postnatally. To further investigate the
      significance of the Na(+)-Ca2+ exchanger during normal myocardial development,
      steady-state mRNA levels of the cardiac Na(+)-Ca2+ exchanger were quantitated by
      Northern blot and slot-blot analyses using poly(A+) RNA isolated from rabbit and
      rat ventricles at various fetal and postnatal ages. Northern analyses were
      performed with a 1.35-kb guinea pig cardiac Na(+)-Ca2+ exchanger cDNA probe.
      Exchanger mRNA levels were quantitated by densitometric scans of the slot blots,
      and results were normalized by reprobing the same blots with 32P 5'-end-labeled
      oligo(dT). In both species, exchanger mRNA levels peaked near birth and declined
      postnatally. Maximal levels were approximately sixfold greater in the late fetal
      rabbit (gestational day 29) and eightfold greater in the early newborn rat
      (postnatal day 1) compared with adults of the respective species. The parallel
      changes in exchanger mRNA and protein levels suggest that developmental
      regulation of cardiac Na(+)-Ca2+ exchanger expression involves pretranslational
      control mechanisms. These results support the concept that during normal cardiac
      development, Na(+)-Ca2+ exchanger expression is maximal near the time of birth
      and then declines postnatally as Ca2+ regulation by the sarcoplasmic reticulum
      reaches functional maturity.

PMID- 8293574
TI  - Ca2+ preconditioning elicits a unique protection against the Ca2+ paradox injury
      in rat heart. Role of adenosine. Fixed.
AB  - Repeated Ca2+ depletion and repletion of short duration, termed Ca2+
      preconditioning (CPC), is hypothesized to protect the heart from lethal injury
      after exposing it to the Ca2+ paradox (Ca2+ PD). Hearts were preconditioned with
      five cycles of Ca2+ depletion (1 minute) and Ca2+ repletion (5 minutes). These
      hearts were then subjected to Ca2+ PD, ie, one cycle of Ca2+ depletion (10
      minutes) and Ca2+ repletion (10 minutes). Hearts subject to the Ca2+ PD underwent
      rapid necrosis, and myocytes were severely injured. CPC hearts showed a
      remarkable preservation of cell structure; ie, 65% of the cells were normal in
      CPC hearts compared with 0% in the Ca2+ PD hearts. LDH release was significantly
      reduced in CPC hearts compared with Ca2+ PD hearts (2.45 +/- 0.18 and 8.02 +/-
      0.7 U.min-1 x g-1, respectively). ATP contents of CPC hearts were less depleted
      compared with the Ca2+ PD hearts (5.9 +/- 0.8 and 3.0 +/- 0.16 mumol/g dry
      weight, respectively). Addition of the adenosine A1 receptor agonist R
      phenylisopropyl adenosine before and during Ca2+ PD provided protection similar
      to that in CPC hearts, whereas the nonselective adenosine A1 receptor antagonist,
      8-(p-sulfophenyl)-theophylline, blocked the beneficial effects of CPC. CPC
      mediated protection was aborted when hearts subjected to CPC were treated with
      pertussis toxin (the guanine nucleotide or G-protein inhibitor). The present
      study suggests that Ca2+ preconditioning confers significant protection against
      the lethal injury of Ca2+ PD in rat hearts. Cardioprotection appears to result
      from adenosine release during preconditioning and by Gi-protein-modulated
      mechanisms.

PMID- 8293575
TI  - Signal transduction--a conserved pathway from the membrane to the nucleus.

PMID- 8293576
TI  - A murine CDC25/ras-GRF-related protein implicated in Ras regulation.
AB  - A partial cDNA encoding a novel putative p2, ras guanine nucleotide release
      inducing factor (GRF), GRF2, was amplified from murine embryonic stem cells. The
      presumptive catalytic region of GRF2 is related to the yeast Ras GRF encoded by
      CDC25. GRF2 is 80% identical to murine CDC25Mm/ras-GRF, but is more similar to
      yeast CDC25 than to other ras GRFs related to the Drosophila son of sevenless
      gene product. A 9-kb GRF2 messenger RNA was highly expressed in brain, but GRF2
      specific antibodies recognized apparent GRF2 proteins in various mouse tissues in
      addition to brain. Thus GRF2 represents a novel widely-expressed protein that is
      highly related to CDC25Mm/ras-GRF, at least in its catalytic domain. Both GRF2
      and CDC25Mm/ras-GRF are expressed in murine embryonic stem cells, suggesting that
      different Ras activators may regulate ras-dependent proliferation and
      differentiation in early mouse development.

PMID- 8293577
TI  - Embryonic and fetal rat myoblasts express different phenotypes following
      differentiation in vitro.
AB  - Myosin heavy chain (MHC) is encoded by a multigene family containing members
      which are expressed in developmental and fiber type-specific patterns. In
      developing rats, primary (1 degree) and secondary (2 degrees) myotubes can be
      distinguished by difference in MHC expression: 1 degree myotubes coexpress
      embryonic and slow MHC, while 2 degrees myotubes initially express only embryonic
      MHC. We have used monoclonal antibodies which recognize the embryonic, slow,
      neonatal, and adult fast IIB/IIX MHCs to examine MHC accumulation in myoblasts
      obtained from hindlimbs of embryonic day (ED) 14 and ED 20 Sprague-Dawley rats
      during differentiation in vitro. Embryonic myoblasts (ED 14), which develop into
      1 degree myotubes in vivo, differentiate as myocytes or small myotubes (i.e., 1-4
      nuclei) which express both embryonic and slow MHC. They do not accumulate
      detectable levels of neonatal or adult fast IIB/IIX MHC. Fetal myoblasts, which
      develop into secondary myotubes in vivo, fuse to form large myotubes (i.e., 10-50
      nuclei) and express predominantly embryonic MHC at 3 days in culture. These
      myotubes accumulate neonatal and adult fast IIB/IIX isoforms of MHC and
      eventually contract spontaneously. In contrast to embryonic myotubes, they do not
      accumulate slow MHC. Our results demonstrate that embryonic and fetal rat
      myoblasts express different phenotypes in vitro and suggest that they represent
      distinct myoblast lineages similar to those previously described in chickens and
      mice. These two lineages may be responsible for the generation of distinct
      populations of 1 degree and 2 degrees myotubes in vivo.

PMID- 8293578
TI  - Developmental requirements for the ecdysoneless (ecd) locus in Drosophila
      melanogaster.
AB  - The ecdysoneless locus in Drosophila melanogaster has been defined previously by
      a single conditional mutation, I(3)ecd1, that causes an ecdysteroid deficit and
      larval death at the restrictive temperature, 29 degrees C, although the primary
      role of the mutation in developmental processes has been unclear. Gene dosage and
      complementation studies reported here for ecd1 and five nonconditional lethal
      alleles indicate that the ecd locus plays prezygotic and postzygotic roles
      essential for normal embryonic development, the successful completion of each
      larval molt, adult eclosion, and female fertility. The ecd locus is also required
      for normal macrochaete differentiation. For each observed phenotype, the severity
      of mutational effects was correlated with ecd mutant genotypes. In all cases,
      ecd1 homozygotes were least affected. Mutants heteroallelic for ecd1 and any one
      of four nonconditional recessive mutations were more severely affected than ecd1
      homozygotes, revealing these as hypomorphic alleles. For all phenotypic effects,
      mutants heteroallelic for ecd1 and a dominant mutation (ecd3D) were most severely
      affected. These individuals died during embryogenesis at 29 degrees C and
      developed no macrochaetes on the dorsal thorax when transferred to 29 degrees C
      during the white prepupal stage. The ecd3D mutation also caused female
      semisterility in heterozygotes. Ecdysteroid regulation has been implicated
      previously in all the developmental processes disrupted by these ecd mutations
      except for macrochaete differentiation.

PMID- 8293579
TI  - Analysis of the subtelomeric regions of macronuclear gene-sized DNA molecules of
      the hypotrichous ciliate Stylonychia lemnae: implications for the DNA
      fragmentation process during macronuclear development?
AB  - The subtelomeric regions of macronuclear gene-sized DNA molecules from
      Stylonychia lemnae were analyzed. The results obtained indicate that these
      regions show a highly ordered and common sequence organization: Immediately
      adjacent to the telomeric sequence a short inverted repeat sequence is found,
      followed by another 7-9 bp inverted repeat sequence at approximately position 40.
      A 10 bp consensus sequence found in the subtelomeric regions of all gene-sized
      DNA molecules is found at approximately position 60 and in addition at about the
      same position palindromic sequences showing no homology to each other are
      localized. The biological significance of this sequence organization is
      discussed.

PMID- 8293580
TI  - Antisense inhibition of nuclear-encoded cytochrome c oxidase subunits IV and VIIc
      activity in the pre-implantation embryo.
AB  - It had not previously been known whether synthesis of nuclear-encoded
      mitochondrial subunits occurs in pre-implantation embryos. We have used
      cytoplasmic injections of antisense RNA transcribed in vitro to study this
      question. Capped, in vitro transcribed RNA antisense to either cytochrome c
      oxidase subunit IV or VIIc injected into each cell at the two-cell stage markedly
      inhibited synthesis of adenine nucleotide by the 8- to 16-cell stage, whereas
      injection of the cognate sense RNAs gave levels similar to those previously
      published for normal embryos. These results strongly suggest that translation of
      nuclear-encoded mRNAs for mitochondrial subunits is required during pre
      implantation development. It was of additional interest that, not only was ATP
      decreased, but ADP and AMP as well, with the effect that the charge ratio
      remained constant. The results also suggest, therefore, that the mechanism by
      which cells normally regulate their charge ratio, though to be with adenylate
      deaminase, is already in place.

PMID- 8293581
TI  - Sea urchin maternal mRNA classes with distinct development regulation.
AB  - Previous studies of newly synthesized proteins during early development in sea
      urchins have revealed several different patterns of synthesis that can be used to
      predict the existence of mRNA classes with distinct regulatory controls. We have
      identified clones for abundant maternal mRNAs that are actively translated during
      early development by screening a cDNA library prepared from polysomal poly(A)+RNA
      isolated from 2-cell stage (2-hour) Strongylocentrotus purpuratus embryos. Probes
      prepared from these cDNA clones and several previously characterized maternal
      mRNA cDNAs were used to compare relative levels of individual mRNAs in eggs and
      embryos and their translational status at various developmental stages. These
      abundant mRNAs can be classified into two major groups which we have termed
      cleavage stage-specific (CSS) and post cleavage stage (PCS) mRNAs. The relative
      levels of the CSS mRNAs are highest during the rapid cleavage stage and decrease
      dramatically at the blastula stage (12-hours). In contrast, PCS mRNAs are present
      at relatively low levels during the rapid cleavage stage and then increase at the
      blastula stage. Polysome partition profiles reveal that CSS mRNAs are translated
      more efficiently than PCS mRNAs in the unfertilized egg, at fertilization, and
      during the cleavage stages. Following the blastula stage, some CSS transcripts
      move out of polysomes and accumulate as untranslated RNAs, while newly
      transcribed PCS mRNAs are recruited into polysomes. These data suggest that the
      rapid cell cycles following fertilization require high levels of specific
      cleavage stage proteins, and the synthesis of these proteins occurs
      preferentially over PCS mRNAs.

PMID- 8293582
TI  - Chorioamnionitis and intraamniotic infection.
AB  - Intraamniotic infection is a common (2-4%) event in labor. The predictors of IAI
      include preterm labor or rupture of membranes, abnormal vaginal flora (e.g., GBS,
      sexually transmitted disease, bacterial vaginosis), obstetric manipulations
      (e.g., vaginal exams, internal fetal monitoring) in the presence of ruptured
      membranes, and diminished host response (due to smoking, drug abuse, obesity,
      immunodeficiency states, etc.). Group B Streptococcus and Enterobacteriaceae are
      the most important organisms associated with the polymicrobial infection.
      Anaerobes predict post-cesarean section complications. Neonatal pneumonia (2-5%)
      and early neonatal sepsis (1-4%) are the outcomes of the greatest concern and are
      caused by group B streptococcal or aerobic gram-negative rod infections. These
      outcomes are kept to a minimum if maternal antibiotic chemotherapy is started
      interpartum with agents that are safe, cross the placenta, and are active against
      GBS and Escherichia coli (e.g., ampicillin plus gentamicin). Anaerobic coverage
      should be added (clindamycin) if a cesarean section is performed. Antipyretics
      such as acetaminophen will reduce the hyperthermic stress on the fetus, and
      persistent fetal tachycardia after antipyretics may indicate fetal infection.
      Continuous electronic fetal monitoring is appropriate in cases of IAI, and
      providers should be prepared for neonatal resuscitation, early neonatal
      intravenous antibiotics, and respiratory support at delivery.

PMID- 8293583
TI  - The Vaginal Infections and Prematurity Study: an overview.

PMID- 8293584
TI  - Human immunodeficiency virus and the obstetrician.

PMID- 8293585
TI  - Management of group B streptococcal disease in pregnancy.
AB  - GBS is a bacterium that may cause devastating disease. The puzzle of GBS
      management revolves around the fact that the organism colonizes 15-30% of women,
      yet produces infection in only 1-3% of the women who are colonized. Neonatal
      infection is acquired from the maternal genital tract. It ascends across the
      cervix into the amniotic cavity and also may be acquired during delivery.
      Manifestations of disease in the fetus and neonate may be out of proportion to
      those in the mother. Treatment strategies involve the screening all pregnant
      women with cultures at 26-28 weeks' gestation and rapid tests at the time of
      labor. Rapid testing has not proven successful, although current research should
      provide effective and sensitive rapid tests by the end of the decade. Once a
      woman is known to be GBS positive in labor, there are two options. Most
      investigators recommend giving chemoprophylaxis only to women who are at high
      risk for GBS infection--women with preterm labor, ruptured membranes for longer
      than 12-18 hours, or intrapartum fever higher than 37.5 degrees C. Others
      advocate treating all GBS carriers regardless of risk status. Treatment of
      mothers in labor eradicates vaginal carriage of GBS, though it does not eradicate
      GBS from the lower digestive tract. Intrapartum chemoprophylaxis decreases the
      incidence of neonatal colonization and significantly decreases the risk of infant
      disease. In the future, GBS infection probably will be prevented with
      immunoprophylaxis and vaccination.

PMID- 8293586
TI  - The ABCs of hepatitis in pregnancy.

PMID- 8293587
TI  - Urinary infection in pregnancy.

PMID- 8293588
TI  - Herpes in pregnancy.

PMID- 8293589
TI  - Viruses, bacteria, and protozoans in pregnancy: a sample of each.
AB  - This article only touches the surface of a very broad subject. As mentioned
      before, the microorganisms covered were chosen with the practitioner in mind. The
      reader will note that many of the syndromes discussed have subtle presentations
      with overlapping symptomatology or essentially no symptoms at all. Clinicians
      therefore must maintain a high degree of suspicion when faced with such
      infectious complications of pregnancy.

PMID- 8293590
TI  - Antibiotics in pregnancy.
AB  - Because it is known that antibiotics given to the mother may reach and affect the
      fetus, when prescribing antibiotics during pregnancy, one must take into
      consideration both maternal and fetal well-being. Therapy should be directed
      toward the maternal disease but also be safe for the fetus. The volume of
      distribution is increased during pregnancy, and dosages may need to be adjusted
      to accommodate this change. Because it is difficult to monitor the toxicity in
      the fetus, the physician must make careful choices when prescribing antibiotic
      treatment for the pregnant patient.

PMID- 8293591
TI  - Anatomy and biomechanics of genital prolapse.

PMID- 8293592
TI  - The muscles of the pelvic floor.

PMID- 8293593
TI  - Pelvic floor disorders: the role of fascia and ligaments.

PMID- 8293594
TI  - Clinical evaluation of women with pelvic support defects.

PMID- 8293595
TI  - Radiology of the pelvic floor.

PMID- 8293596
TI  - Paravaginal repair for cystourethrocele.

PMID- 8293597
TI  - Vaginal hysterectomy with repair of enterocele, cystocele, and rectocele.
AB  - There are several equally effective but different operative procedures to correct
      uterine procidentia; the technique and operative approach must be chosen
      according to the specific needs of the patient. The surgeon must be able to
      dissect, identify, resect, and approximate the appropriate supporting structures.
      To preserve a functional vagina in a patient with complete procidentia, the
      surgeon must have a full understanding of the principles of pelvic support. If a
      functional vagina is unimportant, then a tight, coned-down vagina (one finger in
      depth and diameter) offers the best long-term results.

PMID- 8293598
TI  - The rectovaginal septum revisited: its relationship to rectocele and its
      importance in rectocele repair.
AB  - Using the descriptions of Uhlenhuth, and Milley and Nichols, we have been able to
      identify a sheet of strong connective-type tissue between the rectum and vagina.
      This layer has been named the rectovaginal septum, referred to, by some, as the
      rectovaginal fascia. As it is considered to be analogous to the rectovesical
      septum in men, first described by Denovilliers, some refer to it as
      Denonvilliers' fascia in the female. This layer is immediately beneath the
      vaginal mucosa and clearly is what many would consider part of the vaginal wall.
      Its principal attachments are peripheral--it merges superiorly with the
      cardinal/uterosacral complex, fuses laterally with the fascia over the levator
      muscle, and merges distally into the perineal body. Histologically, it contains
      collagen that is quite dense in places, some strands of smooth muscle, and a very
      dense network of heavy elastin fibers. It is this layer that acts as a supporting
      structure for the perineal body and prevents the rectum from bulging into the
      vagina. Rectoceles represent a defect in this layer that allows the rectum to
      bulge inward. The defects are usually isolated breaks that can be repaired
      directly with excellent and predictable results.

PMID- 8293599
TI  - Vaginal approach to treatment of vaginal vault eversion.

PMID- 8293600
TI  - Abdominal approach to vaginal eversion.

PMID- 8293601
TI  - [Relations between neuropsychological findings and lateral asymmetries of
      cerebral blood flow measured by SPECT in dementia of Alzheimer type].
AB  - We studied 16 right-handed patients clinically diagnosed as dementia of Alzheimer
      type (6 men, 10 women; aged 63-85, mean 72.8 years). The average duration of
      symptoms was 2.7 years. Dementia ranged from mild to moderately severe. None had
      clinical or laboratory evidence of cerebrovascular disease (Hachinski ischemic
      scores for all patients were 4 or below 4). All received the Wechsler Adult
      Intelligence Scale (WAIS), Mini-mental State Test (MMS) and Western Aphasia
      Battery (WAB, First Japanese edition, 1986). Regional cerebral blood flow (rCBF)
      was evaluated by single photon emission CT (SPECT) with 123I-N-isopropyl-p
      iodoamphetamine (123I-IMP), using the Matsuda's quantitative method (Am J Physiol
      Imag 1: 186, 1986). Regional tracer uptake was measured in regions of interests
      (ROIs) over right and left frontal, temporal, parietal and occipital cortical
      regions; basal ganglia; and cerebellar hemispheres. The subjects were divided
      into three groups on the basis of lateral asymmetries in the temporal and
      parietal cortexes of rCBF (left < right, n = 5; right < left, n = 3; left =
      right, n = 8). We decided that lateral asymmetry was present when rCBF for each
      ROI between left and right sides differs by more than 10%. General score (MMS, T
      IQ) was not correlated with asymmetry of cerebral blood flow. Verbal IQ in
      patients with predominant hypoperfusion of left temporal and parietal lobe was
      significantly lower than other group, while performance IQ and WAB constructive
      scores were lower in those with right hemispheric hypoperfusion (p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293602
TI  - [Cerebral circulation and metabolism in patients with mitochondrial myopathies].
AB  - In order to study the cerebral circulation and metabolism in 6 patients with
      mitochondrial myopathies and 6 normal control subjects, positron emission
      tomography with oxygen-15 labelled tracers was performed. Four patients had
      predominantly central nervous system involvement, whereas 2 had myopathy alone.
      In comparison with normal control subjects, patients with mitochondrial
      myopathies showed decreased cerebral blood flow (CBF), decreased cerebral oxygen
      metabolic rate (CMRO2), and low oxygen extraction fraction (OEF) value due to an
      uncoupling of CBF and CMRO2. The reduction of OEF was remarkable in the 2
      patients having predominantly central nervous disease and 1 having myopathy
      alone. We suppose that these findings are greatly related to mitochondrial
      myopathies and that they reflect the disturbance of mitochondrial oxidative
      metabolism in the brain. The patients whose central nervous symptoms progressed
      rapidly tended to show the reduction of OEF, but the degree of the reduction of
      OEF was not necessarily related to the severity of the central nervous symptoms.
      These findings suggest that the disturbance of cerebral metabolism is not uniform
      in patients with the same central nervous disease.

PMID- 8293603
TI  - [Study of patients with spinocerebellar degeneration using positron emission
      tomography].
AB  - We studied cerebral blood flow, oxygen metabolism and their relation to clinical
      symptoms in 45 patients with spinocerebellar degeneration (SCD) and 12 normal
      control subjects using positron emission tomography (PET). Regions of interest
      were acquired for the cerebellar hemispheres, cerebellar vermis, brainstem,
      thalami, and cerebral cortices. PET studies in these patients revealed that
      regional cerebral blood flow (CBF), regional cerebral oxygen metabolic rate
      (CMRO2), CBF/mean CBF of each cerebral cortex (CBF/mCBF) and CMRO2/mean CMRO2 of
      each cerebral cortex (CMRO2/mCMRO2) in the cerebellar hemispheres, cerebellar
      vermis, and brainstem showed a significant decrease in comparison with the normal
      control subjects, while in the cerebral cortices and thalami, SCD patients showed
      normal values. CBF/mCBF and CMRO2/mCMRO2 were significantly decreased in patients
      with olivopontocerebellar atrophy (OPCA) and Menzel type of hereditary ataxia
      (Menzel type) in the cerebellar hemispheres, cerebellar vermis, and brainstem,
      whereas patients with late cortical cerebellar atrophy (LCCA) and Holmes type of
      hereditary ataxia (Holmes type) revealed a significant decrease of CBF/mCBF and
      CMRO2/mCMRO2 in the cerebellar hemispheres and cerebellar vermis, but not in the
      brainstem. Patients with OPCA showed a significant decrease of CBF in the
      cerebellar hemispheres, cerebellar vermis, brainstem and that of CMRO2 in the
      cerebellar hemispheres and cerebellar vermis. Patients with LCCA showed a
      significant decrease of CBF in the right cerebellar hemisphere and cerebellar
      vermis. However, a significant reduction of CBF and CMRO2 was not observed in
      patients with Menzel type or Holmes type in these regions. In patients with LCCA
      and Holmes type, the severity of upper limb ataxia and dysdiadochokinesis were
      significantly correlated with CBF/mCBF and CMRO2/mCMRO2 in the cerebellar
      hemispheres and brainstem.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293604
TI  - [Cranial MRI in hepatic disease--relationship between MR imaging and clinical
      symptoms and laboratory analysis of liver function].
AB  - Magnetic resonance imaging studies on 12 cases with hepatic disease were
      performed. In 11 adult patients with chronic hepatic failure, T1-weighted images
      demonstrated increased signal in the globus pallidus in 7 patients (63.6%) and in
      some parts of the cerebral peduncles in 6 patients (54.5%), in the substantia
      innominata in 4 patients (36.3%). There might be some correlation between the
      abnormality of MR imaging and clinical symptoms of hepatic encephalopathy. There
      was a significant correlation between the intensity of the signal and Fischer's
      ratio of amino acid analysis. In one patient with Wilson's disease, who developed
      symptoms of central nervous system, T1-weighted images demonstrated increased
      signal in the globus pallidus. After treatment of D-penicillamine, the signal of
      the globus pallidus decreased.

PMID- 8293605
TI  - [Age-related changes in nerve action potentials of median nerve--an analysis
      using intraneural neurography].
AB  - Age-related decrease in peripheral nerve conduction velocity and the amplitude of
      sensory nerve action potentials is well established in humans. However,
      evaluation of the sensory nerve action potentials is subject to technical
      constraints because of its small size and variability of the values. To elucidate
      age-related differences, we determined the amplitude of median nerve action
      potentials in 52 healthy individuals aged 16 to 88 years by means of intraneural
      neurography. A tungsten microelectrode was inserted into the median nerve trunk
      at the elbow, and compound nerve action potentials evoked by supramaximal
      electrical stimulation were recorded. The action potentials consisted mainly of
      triphasic waves. Maximal conduction velocity (Y, m/sec) declined very mildly with
      age (X, year), showing the regression line of Y = 67.5 - 0.062X. The peak to peak
      amplitude of the potentials was 466.6 +/- 20.8 (SE) microV and declined gradually
      with a decrement of 13 microV per decade in the individuals under the age of 50
      years. By contrast, in individuals above the age of 50 years, the amplitude (Y,
      microV) declined steeply, showing the regression line of Y = 977.1 - 9.86X (r = 
      0.75, p < 0.001) with age (X, year). A significant correlation was observed
      between amplitude of the sensory nerve action potentials obtained by the
      conventional technique and that obtained by the intraneural neurography.
      Nevertheless, an accelerated decrease was not found in the amplitude of the
      sensory nerve action potentials with age above 50, probably due to the
      variability of the values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293606
TI  - [Autonomic dysfunction in sensory ataxic neuropathy with Sjogren's syndrome].
AB  - Sjogren's syndrome (SjS) is occasionally associated with chronic progressive
      sensory neuropathy, and its major pathology is suggested to be dorsal root
      ganglionitis with the T-lymphocyte invasion. Autonomic dysfunction is frequently
      accompanied by SjS-associated sensory neuropathy but its underlying pathology is
      uncertain. We reported four patients with SjS-associated sensory ataxic
      neuropathy who satisfied the diagnostic criteria of Sjogren's syndrome and also
      showed a wide variety of autonomic disturbances. The sensory involvement was
      initially those of multiple mononeuritis in the distal extremities, but in the
      advanced stage it involved the area distributed along the spinal segmental
      dermatomes particularly in the trunk. Complete anhidrosis with discrete segmental
      distribution, as well as absence of response to cholinergic agents, was observed
      in three cases. Surface skin temperature recorded by a thermoviewer also showed a
      segmental involvement along the spinal dermatomes in two cases. Adie's pupils
      were present in two cases. These features suggested that the segmental
      involvement of the postganglionic sympathetic ganglion cells could be present in
      the underlying pathological condition. As for the other autonomic dysfunction,
      two cases showed severe postural hypotension and three cases had an abnormal
      heart rate variation (R-R interval). Our cases indicated that SjS-associated
      sensory ataxic neuropathy also manifest variable autonomic disturbances and
      suggested that similar pathological process to that involving the dorsal root
      ganglia would be present in the pathology of sympathetic and ciliary ganglion
      cells.

PMID- 8293607
TI  - [Rapid improvement of nerve conduction in a patient with chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP)].
AB  - A patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
      underwent electrophysiological examinations before and three days after high-dose
      intravenous gamma-globulin therapy. In only three days, the distal latency and
      MCV of the right median nerve were markedly improved without change of amplitude
      or configuration of CMAP. Such rapid improvement in conduction velocity might not
      be due to remyelination, because it occurred in only three days. During recovery
      from conduction block after lidocaine administration in normal subjects, the
      distal latency was shortened without the change of its amplitude and
      configuration. This phenomenon is similar to the improvement in the distal
      latency of the right median nerve of this patient after high-dose intravenous
      gamma-globulin therapy. We assume, therefore, that the conduction slowing in CIDP
      should be attributed to inactivation of sodium channels as well as demyelination.

PMID- 8293608
TI  - [A case of acute bilateral interosseous nerve palsy associated with severe
      hypopotassemia].
AB  - A 66-year-old housewife felt mild pains in both her forearms after wringing a
      floorcloth repeatedly while cleaning. The following day she was unable to extend
      her fingers, but could dorsiflex both wrists. A diagnosis of bilateral
      interosseous nerve palsy was made. Laboratory studies revealed severe
      hypopotassemia due to laxative abuse and mild rhabdomyolysis, but her general
      condition was almost good except for the nerve palsies. Nerve conduction studies
      suggested conduction disturbance of the posterior interosseous nerve in both
      forearms. Needle electromyography showed a myogenic pattern in all limbs and a
      neurogenic pattern only in the muscles innervated by the posterior interosseous
      nerve. As the serum potassium was normalized, she recovered rapidly from the
      palsies after only seven days. Repeated electrophysiological studies showed that
      the conduction disturbance and myogenic patterns had disappeared, and only the
      neurogenic pattern remained in the muscles innervated by the posterior
      interosseous nerve. The damage to the posterior interosseous nerve caused by
      repeated pronation and supination of the forearms when wringing a floorcloth was
      probably mild. However, hypokalemic neuromyopathy had probably already decreased
      the muscle membrane excitability, so severe palsy occurred following mild nerve
      damage. The correction of hypopotassemia alone achieved a dramatic improvement of
      the bilateral palsy because muscle excitability was restored. This rare case
      suggests that aggravation of entrapment neuropathy may occur due to hypokalemic
      neuromyopathy.

PMID- 8293609
TI  - [MRI findings in patients with acute autonomic and sensory neuropathy].
AB  - Acute autonomic and sensory neuropathy (AASN), characterized by acute onset of
      extensive autonomic dysfunction and severe sensory deficits, was first described
      by Colan et al. (1978). We present two female patients with AASN in whom magnetic
      resonance imaging (MRI) confirmed such findings in the posterior column of the
      spinal cord. One patient was a 44-year-old woman who developed an upper
      respiratory tract infection followed in 2 weeks by numbness of the limbs and gait
      disturbance. There was orthostatic hypotension with syncope, paretic ileus,
      anhidrosis and urinary retention. There was a loss of sensation over the entire
      body, including the face, and deep tendon reflexes were generally absent.
      Neurophysiologic studies showed that sensory nerve action potentials and SSEPs
      were not evoked in the nerves examined. Sural nerve biopsy demonstrated severe
      axonal degeneration of the myelinated and unmyelinated fibers. Our second
      patient, a 27-year-old woman, exhibited similar clinical and laboratory features.
      The autonomic dysfunction in both patients improved gradually without drug
      treatment, but the sensory deficits--predominantly a loss of deep sensation-
      persisted for several years. In both patients, MRI revealed the T2*-weighted high
      intensity area in the fasciculus gracilis of the posterior column of the spinal
      cord. Such high intensity areas were present in all spinal segments. The severe
      and persistent sensory disturbance in these patients may have been caused by a
      lesion of the posterior column of the spinal cord following the involvement of
      the dorsal root ganglion cells, or ganglioneuronopathy, as demonstrated by MRI.

PMID- 8293610
TI  - [Muscle sympathetic nerve activity (MSNA) in a patient with tetanus].
AB  - Autonomic nervous function was studied in a 57-year-old female patient with
      tetanus of mild degree, by recording muscle sympathetic nerve activity (MSNA)
      using the microneurographic method, as well as by measuring blood pressure, heart
      rate and plasma content of norepinephrine (NE). No apparent clinical signs of
      autonomic dysfunction were observed. Recording of MSNA on the 7th hospital day
      revealed decreased discharge rates compared with age-matched healthy subjects,
      indicating suppressed sympathetic nerve function. The decreased MSNA returned to
      closely normal level after 3 months, when the clinical symptoms and signs were
      almost completely cleared up. Previous studies have shown facilitated sympathetic
      nerve function, while some sympathetic nerves remain suppressed, and therefore
      unstable cardiovascular dysfunction might be elicited in tetanus.

PMID- 8293611
TI  - [Cerebral sinus thrombosis in a young man with hereditary protein C deficiency].
AB  - A 23-year-old man was admitted because of vomiting and severe, progressive
      headache. After admission, he suffered from a generalized clonic seizure, and
      developed right hemiparesis. Contrast-enhanced CT of the brain showed empty delta
      sign in the posterior part of the superior sagittal sinus and filling defect in
      the straight sinus. T2-weighted MRI demonstrated high intensity area in the left
      parieto-occipital subcortical region. Delayed venous phase of the right carotid
      angiography confirmed the diagnosis of thrombosis of the superior sagittal sinus.
      Coagulation studies gave a protein C activity of 35.3% (normal range 55-140%),
      protein C antigen of 45% (normal range 70-150%). Same results were obtained from
      the studies of his father and one of his sisters, indicating hereditary protein C
      deficiency. We started warfarin therapy under the administration of heparin for a
      week, then he has been followed up with no subsequent problems.

PMID- 8293612
TI  - [Study of diffusion weighted magnetic resonance imaging in Wilson's disease].
AB  - We analyzed diffusion weighted magnetic resonance images (diffusion MRI) of the
      basal ganglia, which were obtained from four patients with Wilson's disease, and
      compared them with the images from ten age-matched normal individuals. In all
      patients, T2-MRI of the basal ganglia disclosed low or iso-signals, but diffusion
      MRI revealed abnormal high signals in some areas of the basal ganglia in each
      case. Pathological changes except for copper and/or iron deposits are difficult
      to estimate by T2-MRI because the low signal on T2-MRI emphatically reflects the
      deposits, while the abnormal high signal on diffusion MRI is thought to reflect
      parenchymal lesions such as cell loss, demyelination and/or increase of the
      extracellular fluid. From our results, we confirmed that diffusion MRI was very
      useful for estimating parenchymal lesions with metal deposits.

PMID- 8293613
TI  - [A case of tuberculous meningitis with abnormal contrast enhancement of choroid
      plexus on CT and MRI].
AB  - A 55-year-old man first noted a swelling on his back in September 1990, when CT
      scan of his chest suggested a pleural fistula and a cold abscess. In the
      following month, he became pyrexial and felt nauseated with headache.
      Subsequently he was transferred to our hospital. Results of neurological
      examination were abnormal only in that he had neck stiffness and bilateral
      nystagmus with drowsiness. Cerebrospinal fluid (CSF) showed turbid yellowish
      fluid with an opening pressure of 360 mmH2O, a protein content of 173 mg/dl, a
      glucose level of 19 mg/dl, and a white blood cell count of 3,024/ml (75%
      polymorphs, 25% lymphocytes). Tryptophane test was positive. No bacteria, fungi
      or acid-fast bacilli were seen on direct smear. Adenosine deaminase activity in
      CSF was 13.9 IU/l. Antibiotics, antituberculous drugs, corticosteroids and
      glycerol were administered. The clinical course in the hospital was satisfactory
      for the next two months, but a contrast enhanced CT scan showed prominent
      enhancement in the left choroid plexus, and MRI revealed another mass in the
      subarachnoidal space under the right frontal lobe. An open biopsy was done on the
      massive lesion in the frontal lobe. Macroscopically, this lesion was an
      encapsulated granulomatous one. On the other hand, there were groups of
      epitheloid cells with micronecrosis in their centers microscopically. These
      findings were compatible with tuberculoma, in spite of the absence of acid-fast
      bacilli or caseous necrosis. Medication was intensively continued: a follow-up CT
      showed gradual reduction of the choroid plexus lesion and shrinkage of the left
      lateral ventricle.

PMID- 8293614
TI  - [A case of carbamazepine-induced lupus with myositis].
AB  - This is the report with muscle disorder associated carbamazepine (CBZ)-induced
      lupus. A 39-year-old female had been treated with CBZ 400 mg per day for 2 years
      because of complex partial seizure. In November, 1992 laboratory studies showed
      elevation of serum CK, IgG and titers of antinuclear antibody. Physical
      examination on admission revealed muscle weakness of neck flexors and iliopsoas
      but no rash or arthralgia. The electromyography showed myogenic change in the
      right biceps. CBZ was discontinued and replaced by zonisamide. Prednisolone 40 mg
      daily was started and the patient steadily improved. In the literature, there
      have been a few cases with muscle symptoms in CBZ-induced lupus, but muscle
      involvement with highly elevated CK associated with CBZ-induced lupus has not
      been reported.

PMID- 8293615
TI  - [Pseudohyperkalemia in myotonic dystrophy].
AB  - Serum electrolytes were measured in 14 patients with myotonic dystrophy and 25
      healthy controls. The serum level of sodium was 144.8 +/- 3.2 (mean +/- SD) mEq/l
      in myotonic dystrophy and 142.0 +/- 1.9 mEq/l in the controls, and the level of
      potassium was 4.6 +/- 0.4 mEq/l and 4.0 +/- 0.3 mEq/l, respectively. Both
      electrolyte levels were significantly higher in the disease (p < 0.01, p <
      0.001). Blood samples obtained from 5 patients and 5 controls were allowed to
      stand at room temperature, and serum electrolyte levels were repeatedly measured
      at 5, 30, 60, 120 minutes after blood collection. The measurement of serum
      potassium in myotonic dystrophy was elevated in the parallel with standing-time.
      The serum potassium was significantly higher in the patients than in the controls
      at 60 and 120 minutes standing. These results suggest that myotonic dystrophy has
      red blood cell membrane abnormality which allows potassium to leak.

PMID- 8293616
TI  - [True muscle hypertrophy of the unilateral calf in congenital myotonic dystrophy-
      a case report].
AB  - A 23-year-old female was admitted to our hospital because of unilateral calf
      enlargement. On neurological examination, she was mentally retarded with mild
      dysarthria. Grip myotonia was bilaterally present. Muscle weakness including
      those of face, neck and extremities was noted. The right calf tight and firm on
      palpation, was markedly enlarged with a circumference of 35.0 cm compared with
      30.0 cm on the other side. Computed tomographic scans of the skeletal muscles
      revealed marked hypertrophy in the right triceps surae muscle. Electromyographic
      studies demonstrated persistent myotonic discharge in the hypertrophied
      gastrocnemius muscle. A muscle biopsy specimen obtained from the right
      gastrocnemius showed many hypertrophied muscle fibers, with prominent internal
      and sarcolemmal nuclei. Histographic analysis indicated a hypertrophy factor of
      2,025 for type 1 fibers and 1,102 for type 2 fibers. DNA analysis by Southern
      hybridization technique showed large DNA fragment, consistent with congenital
      myotonic dystrophy. In the present patient, unilateral calf enlargement was an
      unusual feature associated with myotonic dystrophy. Neuroradiological and
      pathological studies confirmed true muscle hypertrophy of unilateral calf muscle.
      A search of the literature failed to reveal any case similar to our patient.

PMID- 8293617
TI  - [Tissue variability of androgen receptor gene in bulbospinal muscular atrophy-
      comparison of the number of CAG repeats between muscles and peripheral blood
      leukocytes].
AB  - We investigated an expansion of CAG repeats in exon 1 of androgen receptor gene
      in skeletal muscle tissue obtained from the patients with various neuro-muscular
      disorders (5 BSMA, 33 patients with amyotrophic lateral sclerosis, 3 patients
      with spinal progressive muscular atrophy and 2 patients with hereditary motor
      sensory neuropathy), by polymerase chain reaction (PCR) amplification according
      to LaSpadas' description. These muscle tissues had been stored at -70 degrees C
      freezer during 7 years. We also studied the tissue variation of CAG repeats size
      between muscles and peripheral blood leukocytes in 4 patients with BSMA. And we
      confirmed the increased number of CAG repeats in all 5 BSMA except for other
      patients with neurogenic muscular atrophy. In the 4 BSMA patients, we subcloned
      the PCR products from muscles tissues and peripheral blood leukocytes, and we
      determined the number of CAG repeats by sequencing. The repeats of them were 43
      51, and all BSMA patients showed the same number of CAG repeats in muscles
      tissues and peripheral blood leukocytes. The CAG repeats fragment of BSMA may be
      stable region in frozen storage state for 7 years, and we didn't recognized the
      somatic variation at least between muscles tissues and peripheral blood
      leukocytes.

PMID- 8293618
TI  - Intense gallium-67 uptake in ovarian dysgerminoma.
AB  - In a patient with an ovarian dysgerminoma, intense uptake of gallium-67 citrate
      was demonstrated. This report indicates that dysgerminoma should be added to the
      list showing abnormal accumulation of gallium-67 citrate in the abdomen.

PMID- 8293619
TI  - Congenital or early developmental versus later acquired renal function asymmetry.
      Scintigraphic characteristics.
AB  - A congenitally or developmentally small right kidney in an adult spinal cord
      injury patient had only 12% of total uptake on radioiodine-labeled
      orthoiodohippurate renography but nevertheless had a normal-shaped time-activity
      curve. In a subsequent retrospective review of 175 consecutive radioiodine
      labeled orthoiodohippurate renograms performed on adult patients over a 3-year
      period, 35 other patients with studies showing greater than 2:1 asymmetry in
      renal function were identified. Uptake, clearance, or both were abnormal in all
      35 kidneys with less than 33.3% of function, with the left kidney more commonly
      affected (n = 24). Correlation from ultrasound, computerized tomography,
      intravenous pyelography, and angiography demonstrated acquired abnormalities
      associated with all 35 of these kidneys, including urinary obstruction (n = 20),
      renal artery stenosis (n = 9), and cortical scarring/infection and/or reflux (n =
      15) (some patients had more than one diagnosis). While acquired renal function
      asymmetry almost always results in a smaller kidney with abnormal uptake or
      clearance characteristics, a congenitally small kidney may have overall reduced
      blood flow but still display a normal-shaped time-activity curve on radionuclide
      renography.

PMID- 8293620
TI  - Potentially misleading bone scan findings in patients with hepatoblastoma.
AB  - Eleven patients who underwent nuclear medicine bone scanning were reviewed to
      determine the incidence of bone scan abnormalities associated with
      hepatoblastoma. Of these, six patients had abnormal bone scan findings--four with
      focal involvement. Correlating plain radiographs and/or follow-up nuclear bone
      scans were available for three of these four. All plain films indicated the
      presence of osteoporosis. Follow-up scans showed improvement or resolution of
      abnormalities. None of the patients had documented metastatic bone disease. While
      there has been no prior reported association, the authors attribute the abnormal
      bone scan findings to a paraneoplastic syndrome of osteoporosis associated with
      this primary tumor. They conclude that bone scanning is not routinely indicated
      in the initial diagnostic staging of hepatoblastoma.

PMID- 8293621
TI  - Tc-99m HMPAO brain perfusion SPECT in acute aphasia. Correlation with clinical
      and structural findings.
AB  - Tc-99m hexamethylpropylene amineoxime (HMPAO) brain perfusion SPECT was
      correlated with CT, MRI, and clinical findings in 17 patients with acute and
      subacute aphasia to determine its diagnostic potential in the early phases of
      stroke-associated language dysfunction. SPECT was performed using a dedicated
      brain imaging system after intravenous injection of 20 mCi (740 MBq) of Tc-99m
      HMPAO. Transaxial and three-dimensional surface rendered images were evaluated
      visually, and perfusion defects were correlated with CT, MRI, and a standard
      battery of clinical tests for aphasia. Clinical examination was insufficient for
      anatomic localization of aphasia in more than 40% of patients. CT exams were
      normal in 5 patients, although SPECT demonstrated perfusion defects in all 17.
      Nonfluent aphasia was present in only 6 of 10 patients with perfusion defects in
      Broca's area and fluent aphasia was present in only 5 of 10 patients with lesions
      in Wernicke's area. Auditory comprehension defect was associated with perfusion
      defects in the inferior parietal region in 9 of 12 patients (P = 0.05); reading
      and writing abnormalities were associated with perfusion defects in the posterior
      frontal, superior and inferior parietal cortex, and superior temporal gyri, and
      repetition deficit was associated with defects involving the inferior parietal
      cortex, the supramarginal and angular gyri, and the ipsilateral thalamus in 8 of
      11 patients (P < 0.05). Brain perfusion SPECT should be included in the initial
      evaluation of aphasic patients, because clinical tests of aphasia and
      morphological imaging have limited value for accurately determining the extent
      and location of functional deficits.

PMID- 8293622
TI  - The significance of isolated gallium-67 uptake in the hilar lymph nodes of an
      untreated lymphoma patient.
AB  - A 69-year-old woman presented with non-Hodgkin's lymphoma of the right
      ilioinguinal region in whom bilateral uptake of Ga-67 in hilar lymph nodes was
      noted on thoracic SPECT. There were no Ga-67 abnormalities elsewhere within the
      thorax, and a chest CT scan was also normal. The patient received radiotherapy to
      the inguinal region and remained in clinical remission for 28 months following
      treatment. She subsequently relapsed at a number of peripheral lymph node sites,
      but not in the chest. The authors postulate that isolated hilar uptake of Ga-67
      SPECT may not be clinically significant in some untreated patients with lymphoma.
      This scintigraphic finding should be interpreted cautiously, particularly when
      other chest imaging studies remain negative.

PMID- 8293623
TI  - Successful treatment of idiopathic retroperitoneal fibrosis with steroid
      administration in a patient with a positive gallium scan.
AB  - A patient with idiopathic retroperitoneal fibrosis with a positive Ga-67 scan was
      successfully treated with steroids. Administration of methylprednisolone improved
      the ureteral obstruction and gallium accumulation also disappeared.

PMID- 8293624
TI  - Technetium-99m labeled micro aerosol "Pertechnegas". A new agent for ventilation
      imaging in suspected pulmonary emboli.
AB  - In this preliminary study, four patients suspected of having pulmonary emboli
      underwent ventilation imaging after inhaling approximately 1 mCi (37 MBq) of Tc
      99m Pertechnegas (micro aerosol carbon particles labeled with Tc-99m) in five
      breaths or less. Planar images in multiple projections were recorded for preset
      counts. A final posterior image was acquired to evaluate residual lung background
      activity. Immediately following ventilation imaging, perfusion imaging in the
      identical projections was performed using 4 mCi (148 MBq) of Tc-99m MAA. Two of
      the four patients demonstrated matched uniform ventilation and perfusion and two
      showed segmental ventilation-perfusion "mismatched" defects consistent with
      pulmonary emboli. In each case, residual Pertechnegas background lung activity
      (count rate) at the end of the last ventilation image was less than 10% of the
      initial Tc-99m MAA counts (count rate). The advantages of Pertechnegas, in
      comparison to aerosolized DTPA, include: less residual ventilation image activity
      superimposed on the MAA perfusion images, reduced demand for patient cooperation
      due to fewer required breaths (five or less), and lack of deposition of activity
      in the central airways. The authors conclude that Pertechnegas has properties
      that make it ideally suited for routine lung ventilation imaging.

PMID- 8293625
TI  - The MIBG super scan. Description and therapeutic implications.
AB  - The author reports a case of metastatic pheochromocytoma to bone imaged with 1
      131 MIBG. The "MIBG super scan" pattern is described and is characterized by
      marked increased uptake in bone with essentially complete absence of activity in
      the liver and bladder. The avid bony metastases "steal" activity from the liver,
      as well as from the kidneys and soft tissues. This is felt to be comparable to
      the "super scan" in bone scintigraphy, whereby bony metastases "steal" activity
      from the kidneys and soft tissues.

PMID- 8293626
TI  - "Insular" carcinoma of thyroid. A subset of anaplastic thyroid malignancy with a
      less aggressive clinical course.
AB  - Insular carcinoma of the thyroid appears to represent an entity situated
      morphologically and biologically in an intermediate position between the well
      differentiated and undifferentiated (anaplastic) tumors. The retention of I-131
      concentrating ability by this variant, unlike anaplastic, is very encouraging and
      amenable to detection and therapy by radioiodine after initial aggressive
      surgery. A 46-year-old man with a histologic label of anaplastic thyroid
      carcinoma has had an unusually prolonged disease-free survival and
      histopathologic review confirmed insular carcinoma. Postoperative radioiodine
      evaluation revealed avid concentration of tracer in the thyroid bed. Thus, it is
      possible to ablate with radioiodine. The insular carcinoma should be considered
      as a distinct clinicopathologic entity and widespread awareness of this variant
      of tumor may help pathologists, surgeons, and nuclear medicine practitioners to
      aggressively treat the condition after initial diagnosis.

PMID- 8293627
TI  - Abnormal ambulatory left ventricular ejection fraction in heart transplant
      arteriopathy.
AB  - The morbidity and mortality from heart transplantation has been reduced
      dramatically over the last several years. However, the long-term survival in
      heart transplant recipients is limited by arteriopathy in the allograft coronary
      arteries, the pathophysiology of which is poorly understood. The diagnosis of
      this arteriopathy is at present limited to cardiac catheterization. Noninvasive
      studies have proven to be of limited benefit in diagnosing this arteriopathy. The
      authors performed cardiac vest studies in nine heart transplant recipient
      patients. Six of the vest studies were abnormal; five of the patients had
      documented transplant coronary artery disease by cardiac catheterization. They
      found that the sensitivity and negative predictive value of the cardiac vest in
      identifying arteriopathy in transplant recipients was 100%. The authors propose
      that cardiac vest could be a sensitive, noninvasive screening test for
      identifying arteriopathy in heart transplant recipients.

PMID- 8293628
TI  - Indium-111 leukocyte uptake in a patient with osseous metastatic Ewing's sarcoma.
AB  - A case of increased uptake of in-111 labeled leukocytes in osseous metastasis
      from Ewing's sarcoma is presented. Bone scan and MRI findings were concordant
      with the indium scan, and biopsy confirmed Ewing's metastasis. Although
      relatively specific for infection, indium infrequently does demonstrate abnormal
      bone uptake in several malignancies. This case report is the first to describe
      indium uptake in osseous metastatic Ewing's sarcoma. Possible mechanisms of
      indium leukocyte localization are discussed.

PMID- 8293629
TI  - Regional cerebral blood flow changes in stroke imaged by Tc-99m HMPAO SPECT with
      corresponding anatomic image comparison.
AB  - Cerebral infarction is the result of cerebrovascular insufficiency and itself
      creates complex changes in cerebral hemodynamics. To allow recognition of
      patterns of change in regional cerebral blood flow (r-CBF) caused by cerebral
      infarction, the authors present an atlas of Tc-99m hexamethylpropyleneamine oxime
      (Tc-99m HMPAO) SPECT brain scan sections for a variety of strokes demonstrating
      typical vascular territorial involvements and evolution of morphologic and r-CBF
      change. Sections from MRI or CT are shown with SPECT images of the stroke lesion
      for comparison of the complementary information provided by regional
      cerebroperfusion and by morphology. Examples of SPECT during acute, subacute, and
      chronic stages of stroke are provided. To illustrate the temporal evolution of
      stroke and accompanying changes in the "stroke penumbra," case examples of acute
      tissue necrosis, luxury perfusion, ischemia, and diaschisis are presented.
      Methods for semiquantitative analysis of morphologic versus r-CBF defect size
      after acute stroke are described. How brain SPECT scans conducted during Diamox
      initiated cerebrovascular stress tests can complement the information obtained
      from baseline studies and assist in the interpretation of r-CBF abnormalities is
      also demonstrated.

PMID- 8293630
TI  - Bone marrow uptake complicating radionuclide venography in a patient with sickle
      cell anemia.

PMID- 8293631
TI  - Renal bed recurrence of renal cell carcinoma detected on the vascular phases of
      dynamic skeletal scintigraphy.

PMID- 8293632
TI  - Surprise struma. Suppurative thyroiditis found by In-111 WBC imaging.

PMID- 8293633
TI  - Comparative imaging. Septic pulmonary embolus.

PMID- 8293634
TI  - Internal mammary artery artifact on bone scan of post-CABG patient.

PMID- 8293635
TI  - Pericardial effusion secondary to severe hypothyroidism demonstrated by Tl-201
      myocardial scintigraphy.

PMID- 8293636
TI  - Internal biliary fistula after cholecystectomy.

PMID- 8293637
TI  - A doubtful image of Le Veen shunt patency.

PMID- 8293638
TI  - Radionuclide ventriculogram in cor pulmonale secondary to multiple pulmonary
      emboli.

PMID- 8293639
TI  - Phantom infection in asymptomatic vessels.

PMID- 8293640
TI  - Computed tomography or magnetic resonance imaging for axillary symptoms following
      treatment of breast carcinoma? A randomized trial.
AB  - Fifty-eight patients presenting with axillary symptoms (pain, oedema, etc)
      following radiation therapy for breast carcinoma were randomized to be
      investigated by either computed tomography (CT: 29 patients) or magnetic
      resonance imaging (MRI: 28). The objectives of the study were to compare the
      efficacy of the two tests in identifying the presence of tumour and their
      effectiveness as judged by quality of life (QOL) outcome measurements. Both tests
      proved efficacious; the predictive values for a positive result (tumour present)
      were 100% for both tests; the predictive values for negative findings were in the
      range of 76 to 90% for CT and 81 to 100% for MRI. As regards outcome, complete
      QOL data were available in 37 patients (17 of these patients had CT, 20 MRI).
      Although the mean change in QOL over 6 months was slightly more favourable in the
      patients investigated by MRI than in the CT group, the difference did not reach
      statistical significance.

PMID- 8293641
TI  - Computed tomography of the lung in Wegener's granulomatosis.
AB  - Computed tomography of the thorax was performed in 30 patients with Wegener's
      granulomatosis to define the anatomical basis of pulmonary involvement. A wide
      variety of parenchymal and bronchial abnormalities was demonstrated in addition
      to the cavitary nodules commonly described. The high incidence (40%) of bronchial
      abnormalities in these patients may suggest that bronchocentric injury is more
      important in the pathogenesis of lung involvement in this disease than has
      previously been considered. Serial scans in individual patients showed broad
      correlation between the extent of the pulmonary abnormalities and the clinical
      and immunological markers of disease activity.

PMID- 8293642
TI  - The use of the Wallstent endovascular prosthesis in the treatment of malignant
      obstruction of the superior vena cava.
AB  - Seventeen patients (10 men and seven women) aged 48-76 years (mean 63.4) who were
      suffering from malignant superior vena caval obstruction had Wallstents implanted
      percutaneously to relieve the obstruction. Fifteen of the patients had previously
      been treated by radiotherapy or chemotherapy, with either failure to remit or
      later recurrence. Six patients required thrombolysis prior to stenting. All
      patients had rapid relief of the obstructive symptoms. This was sustained in 15
      patients to date or at death. Two patients, both of whom had pre-stent lysis,
      developed stent thrombosis following withdrawal of anticoagulation at 4 months
      and 7 days respectively. Stenting has been shown to be extremely effective at
      relieving superior vena caval obstruction in these patients and is usually the
      only method available in this condition when other treatments fail. Whether all
      patients presenting with malignant superior vena caval obstruction should be
      stented de novo remains to be proven.

PMID- 8293643
TI  - Imaging neuroendocrine tumours with radiolabelled somatostatin analogues and X
      ray computed tomography: a comparative study.
AB  - Various endocrine neoplasms, including a number of carcinoid and pancreatic islet
      cell tumours, express somatostatin receptors. These tumours may be difficult to
      localize using conventional techniques. Radiolabelled somatostatin analogues 123I
      Tyr-3-octreotide and 111In-pentatreotide have been used for imaging these
      tumours. In a retrospective study of 24 patients, the sensitivities of
      somatostatin receptor scintigraphy and X-ray computed tomography (CT) were
      compared. Ten patients were scanned using 123I-Tyr-3-octreotide and 14 with 111In
      pentatreotide. All patients had CT scans. Twenty patients had neuroendocrine
      tumours with a total of 45 lesions in the anatomical areas included on both
      scans. CT detected 42 while somatostatin receptor scanning detected 31 of these
      lesions. Three lesions were missed by CT which were detected by scintigraphy, and
      there were six CT false positive lesions. In a further four patients investigated
      for suspected neuroendocrine tumours, no lesion was shown using either modality
      and subsequent investigations and clinical follow-up have shown no evidence of a
      tumour. We conclude that while CT is more sensitive than somatostatin receptor
      scintigraphy, the techniques are complementary, especially in patients with
      disseminated pathology, equivocal lesions on CT, or a negative CT and strong
      clinical or biochemical evidence of a neuroendocrine tumour.

PMID- 8293644
TI  - 99mTc-MDP scintigraphy in ankylosing spondylitis.
AB  - 99mTechnetium-MDP bone scintigrams in 11 patients with ankylosing spondylitis
      were reviewed. Increased activity in sacroiliac joints was present in five of 11
      cases, all of whom had symptoms of less than 5 years duration. Patients with
      longstanding disease had normal or low sacroiliac joint activity. In the spine,
      appearances included diffuse symmetrical, unifocal or multifocal asymmetrical
      increased uptake involving the costovertebral, costotransverse and facet joints
      as well as the spinous processes. In advanced disease with extensive ankylosis,
      the lumbar spine was featureless on scintigraphy, except for focal increased
      activity at the site of previous fracture in one patient. Of six available views
      of the sternum, increased uptake was present in five at the manubriosternal joint
      and five at the sternoclavicular joints. Increased peripheral uptake was mainly
      in the hips and knees in advanced cases. Plain radiographic changes correlated
      poorly with scintigraphic changes, scintigraphy detecting considerably more
      lesions than radiography. Awareness of the scintigraphic appearances of
      ankylosing spondylitis may lead to diagnosis before the development of
      radiographic changes and avoid confusion with other pathology. Clinical
      indications for bone scintigraphy in ankylosing spondylitis are suggested.

PMID- 8293645
TI  - Scaphoid fracture: a new method of assessment.
AB  - The value of colour flow Doppler ultrasound scanning in patients with suspected
      acute carpal scaphoid fracture has been examined. A prospective study of 78
      patients with signs and symptoms of carpal scaphoid injury was undertaken over a
      period of 6 months. Both wrists of all patients were scanned within 12-72 h of
      injury. The radial artery and carpal scaphoid bone contours are visible using
      this type of imaging technique. The distance between the medial wall of the
      radial artery and the outer cortex of the scaphoid waist was measured. The
      scaphoid index is described and was calculated from this measurement. Patients
      were managed without knowledge of the ultrasound imaging result, using plain
      radiographs and clinical examination as the standard for determining the presence
      of a scaphoid fracture. All patients were followed to the resolution of symptoms.
      All 12 patients who were subsequently considered to have scaphoid fractures were
      identified using this imaging technique within 12-72 h after injury. We conclude
      that this imaging may be useful in the assessment of patients with carpal
      scaphoid fracture. It can be used early, as a supplementary investigation, in
      patients with suspected carpal scaphoid fracture in whom the initial plain
      radiographs are normal.

PMID- 8293646
TI  - Transabdominal ultrasonography as the primary investigation in patients with
      suspected Crohn's disease or recurrence: a prospective study.
AB  - Traditionally, patients with suspected or known and possible recurrent Crohn's
      disease have been investigated by small bowel barium radiology, which incurs a
      relatively high radiation dose. Despite patient selection a significant number
      have a normal barium examination. A prospective study was performed to evaluate
      the use of transabdominal ultrasound as the initial investigation in these two
      groups. One hundred and twenty-seven patients were examined, including 31 with a
      previous history of Crohn's disease. In the known Crohn's disease group there
      were 14 true positive ultrasound examinations and eight true negative, with six
      false positive and three false negative examinations. In the 96 patients not
      previously known to have Crohn's disease, there were 18 true positive and 70 true
      negative examinations, with two false positive and six false negative
      examinations. The overall sensitivity for ultrasound was 78% with a specificity
      of 91%. A significant learning curve was apparent in the early stages of study;
      in the last 64 patients the sensitivity was increased to 87%. These data support
      the use of ultrasound as the initial investigation in patients with suspected
      Crohn's disease or recurrence, prior to consideration for small bowel barium
      radiology, to reduce the large number of unnecessary small bowel barium
      examinations currently being performed.

PMID- 8293647
TI  - Signal intensity patterns in intraspinal dermoids and epidermoids on MR imaging.
AB  - Retrospective evaluation of MR images of nine intraspinal dermoid (n = 4) and
      epidermoid (n = 5) tumours was undertaken. T1-weighted images were available in
      all the patients while proton density (PD) and T2-weighted images were available
      in seven patients. Except for one lesion (only T1-weighted images were available
      in this case), all the lesions were clearly delineated on MR images. Most (5 out
      of 7) were better appreciated on T1- and PD-weighted images than on T2-weighted
      images. On T1-weighted images, the epidermoids were either iso- to mildly
      hypointense to the cord (n = 3), isointense to CSF (n = 1) or markedly
      hyperintense (n = 1). On the PD images, the epidermoids were either isointense to
      cord (n = 3) or markedly hyperintense (n = 1). All the lesions were iso- to
      hyperintense to CSF on T2-weighted images. Of the four dermoids three showed a
      mixed intensity pattern on all sequences; the dominant component gave short T1
      and short T2 values, consistent with fat. The fourth lesion showed homogenous
      material with a signal intensity intermediate between that of CSF and cord on T1
      weighted images. Dermal sinus tracts were present in four of the nine patients;
      three patients had an intraspinal component. This study shows that although MR
      imaging is excellent for their detection, it cannot differentiate the two tumour
      types.

PMID- 8293648
TI  - Double reading of mammography screening films--one radiologist or two?
AB  - The effect of double reading on the number of breast cancers detected and the
      number of women recalled was examined in 15,457 women aged 50-59 years attending
      for mammographic breast screening. All the screening mammograms were interpreted
      independently by two radiologists without knowledge of each other's findings. All
      the cases selected by either radiologist were then reviewed by both radiologists
      and a consensus decision made on whom to recall for further studies. This method
      of double reading increased the number of breast cancers detected by 9% (P <
      0.05) and decreased the number of women recalled by 45% (P < 0.001). Double
      reading of mammography screening films together with consensus decisions on the
      selected cases is recommended.

PMID- 8293649
TI  - Angiographic prediction of dissection followed by ischaemic complications during
      coronary angioplasty.
AB  - Ischaemic problems occur in about 8% of coronary angioplasties and are the major
      cause of morbidity and mortality associated with the procedure. Although the
      ischaemic event is usually due to acute vessel closure due to vessel dissection,
      it is noteworthy that 80-90% of radiographically visible dissections cause no
      problem. We have reviewed 200 consecutive coronary angioplasties in order to find
      predictive factors for those patients likely to suffer dissection followed by
      ischaemic complications. Thirty-four (17%) of the patients undergoing coronary
      angioplasty had radiographically visible dissections, of whom 12 (35%) suffered
      ischaemic complications. There were 16 (8%) major ischaemic complications
      following angioplasty. In four of these cases no obvious dissection was visible
      within the vessel. Eight out of a subgroup of 16 patients who had sequential
      stenoses along one vessel dilated at angioplasty had a dissection. Six of these
      eight patients suffered a major ischaemic complication following the dissection.
      Thus in this group of patients, sequential stenosis not only conferred a high
      probability of dissection during angioplasty but additionally carried an
      increased risk of ischaemic complications following the dissection. Awareness of
      this may affect case selection and may indicate the need for early re-examination
      of the vessel should problems occur following angioplasty.

PMID- 8293650
TI  - Case report: saccular aneurysm of the azygos vein simulating a paratracheal
      tumour.
AB  - We present a case of a large saccular aneurysm arising from the azygos arch in an
      asymptomatic 62-year-old man. Chest radiography showed a well-defined right
      paratracheal mass. Dynamic computed tomography revealed marked enhancement of the
      mass suggesting a vascular structure, but no flow void was demonstrated on
      magnetic resonance imaging, probably due to slow turbulent flow.

PMID- 8293651
TI  - Case report: transcatheter renal embolization to effect renal ablation in
      recurrent PUJ obstruction in a patient with haemophilia.
AB  - We present a case of embolic ablation of a kidney with recurrent infected
      hydronephrosis in a patient for whom surgical resection was considered
      undesirable. The hydronephrosis recurred after embolization using gelfoam/steel
      coils but after a second embolization using lipiodol/absolute alcohol (50/50),
      the patient has remained asymptomatic. More than one embolization procedure may
      be necessary to effect renal ablation. Careful evaluation is necessary to
      determine whether ablation has been achieved. We recommend lipiodol/absolute
      alcohol as the embolic agent of choice.

PMID- 8293652
TI  - Carotid angioplasty and sinus arrhythmias.

PMID- 8293653
TI  - Liver hamartomas in tuberous sclerosis.

PMID- 8293654
TI  - Pontine myelinolysis in a normonatraemic alcoholic.

PMID- 8293655
TI  - What's causing that child's chronic cough?

PMID- 8293656
TI  - Neuropsychology of child psychopathology.

PMID- 8293657
TI  - Cholesterol in infants' diet.

PMID- 8293658
TI  - Current concepts in hearing assessment of children and adults.

PMID- 8293659
TI  - Advances in pediatric endoscopy.

PMID- 8293660
TI  - Neonatal skin care.

PMID- 8293661
TI  - Health care for the adolescent female.

PMID- 8293662
TI  - The little wheezer.

PMID- 8293663
TI  - Distribution of alpha B-crystallin in the anterior segment of primate and bovine
      eyes.
AB  - The presence and distribution of alpha B-crystallin in the anterior segment of
      human, monkey and bovine eyes was investigated immunocytochemically. In all three
      species the most intense staining was seen in the lens and in the nonpigmented
      and pigmented epithelial cells covering the tips of the pars plicata of the
      ciliary body. The staining intensity of the ciliary epithelial cells was
      comparable to that seen in the lens fibers. Strong labeling was also found in the
      corneal endothelium. In bovine eyes the presence of alpha B-crystallin in lens,
      ciliary epithelium of the pars plicata and corneal endothelium was also shown by
      biochemical analysis using SDS-PAGE and immunoblotting.

PMID- 8293664
TI  - Ophthalmological study of the lesions induced by the filarial worm with dermal
      microfilariae, Monanema martini, in its murid hosts.
AB  - The filaria Monanema martini with skin-dwelling microfilariae induces in its
      natural murid hosts lesions similar to those in human onchocerciasis. This was
      demonstrated by histo-pathological studies but it appeared useful to evaluate the
      model by a clinical investigation. An ophthalmological analysis was performed on
      the two species of hosts, inoculated by one, two, or multiple doses of larvae,
      and with infections of at least one year duration. A total of 140 eyes was
      examined (anterior and posterior segments). We established a system for
      enumerating the different types and severities of lesions. We prepared a file for
      each eye and attempted to quantify our observations. The significant lesions were
      different in the two host species. In Arvicanthis niloticus, in which motile
      microfilariae were seen in the anterior segment, punctate keratitis was
      predominant. In Lemniscomys striatus, the posterior segment showed complete
      chorioretinal atrophy, similar to the final stage of onchocercal chorioretinitis
      in humans. M. martini represents in its natural hosts two complementary models
      for the study of the pathogenesis and treatment of human onchocerciasis.

PMID- 8293665
TI  - Immunolocalization of growth factors in the human ciliary body epithelium.
AB  - Although various growth factors have been identified in the human aqueous humor,
      their sources have not been fully established so far. To determine, whether the
      ciliary body epithelium is capable of producing growth factors in vivo, we
      studied the immunolocalization of EGF, bFGF, IGF-I, TGF-alpha, TGF-beta and PDGF
      AB in human ciliary body tissue obtained from 20 autopsy eyes (12 to 88 years;
      fixed within 6 hours post mortem) and 1 surgically enucleated melanoma eye using
      light and electron microscopic immunohistochemistry. Antibody binding was
      visualized by indirect immunofluorescence and immunogold labeling on differently
      fixed frozen and resin-embedded sections. The immunohistochemical findings
      indicate the production of EGF, bFGF, IGF-I, and TGF-alpha, to a minor degree
      also TGF-beta, particularly TGF-beta 2, by the ciliary epithelial cells,
      predominantly the nonpigmented cells. Ultrastructural evidence for an endogenous
      production included the distinct and specific labeling of secretory organelles
      (rough endoplasmic reticulum, Golgi complex), cytoplasmic vesicles, and the
      basolateral membrane infoldings. The ciliary epithelium failed to stain
      significantly with antibodies to TGF-beta 1 and PDGF-AB. Labeling for bFGF was
      found to depend on the specific antibodies and fixation conditions employed.
      Sequestration of bFGF and PDGF-AB in the basement membranes of the ciliary
      epithelium could be demonstrated under certain conditions. Peaks of labeling
      intensity were consistently observed at the crests of the ciliary processes and
      in the pars plana, suggesting regional variations in activity and secretion of
      growth factors into the aqueous humor and vitreous. While only PDGF-AB may be
      derived from the serum, it appears likely that most growth factors demonstrated
      are not circulating hormones but rather act as autocrine and/or paracrine
      factors.

PMID- 8293666
TI  - A natural history study of experimental Staphylococcus epidermidis
      endophthalmitis.
AB  - The purpose of this study was to find a "threshold" quantity of organisms (i.e.
      inoculum) to produce clinical endophthalmitis and determine the natural course of
      intravitreal bacterial counts following inoculation in a rabbit model of
      Staphylococcus epidermidis endophthalmitis. S. epidermidis endophthalmitis was
      induced experimentally in 18 New Zealand white rabbits. Eyes were injected with
      2.0 x 10(3) (Group I: n = 3), 2.0 x 10(4) (Group II: n = 3), 3.0 x 10(5) (Group
      III: n = 3), 3.0 x 10(6) (Group IV: n = 3), 3.0 x 10(7) (Group V: n = 3), or 3.0
      x 10(8) (Group VI: n = 3) organisms. Serial quantitative bacterial cultures
      (colony counts) were performed on the vitreous every eight hours for 9 days. All
      eyes in Groups I and II became culture negative by 24-64 hours post-inoculation
      (PI). All eyes in Groups III-VI remained culture positive [approximately 600-4000
      colony forming units (CFU) per cm3] at 48 to 72 hours PI and were stable for the
      remainder of the nine day study period. Previous work suggests that the host's
      inflammatory response is more important than had been recognized. Previous rabbit
      models of infectious endophthalmitis are known to become culture negative
      ("autosterilized") despite continued intraocular inflammation. This rabbit model
      demonstrates a "threshold" of infection where the host's immune response is
      overwhelmed and "autosterilization" does not occur. When inoculated with 3.0 x
      10(5) or greater S. epidermidis organisms of this strain, continued active
      bacterial replication can now be studied in the rabbit.

PMID- 8293667
TI  - Aberrant expression of the gene for lens major intrinsic protein in the CAT
      mouse.
AB  - Immunocytochemistry fails to detect expression of the lens major intrinsic
      protein (MIP) in 16-day embryos of the congenitally cataractous mouse, CAT, which
      inherits a dominant mutation assigned to the distal end of mouse chromosome 10.
      In situ hybridisation, however, detects MIP mRNA in CAT embryo lens fibre cells
      at a level approximating 60% of that detected in embryonic lens fibres of the non
      cataractous MF1 mouse. Northern blot hybridisation reveals that the most abundant
      MIP mRNA transcript in the adult CAT lens is truncated when compared to that in
      the adult MF1 lens. The results are consistent with a cataractogenic mutation in
      the mouse gene for MIP (Mip) which has also been mapped to the distal end of
      mouse chromosome 10.

PMID- 8293668
TI  - Adhesion molecule expression in acute and fibrotic sympathetic ophthalmia.
AB  - Samples of iris ciliary body, choroid and retina from normal eyes and from 2
      cases of sympathetic ophthalmitis (one acute and one late stage fibrosis) were
      examined for the expression of the VLA integrins beta 1 and alpha 1-6, and the
      integrin beta 3, in addition to ICAM-1, VCAM-1, ELAM-1 and CD44 using an APAAP
      staining technique. The expression of VLA-4, VLA-5, VCAM-1, ICAM-1, and CD44 was
      significantly increased and ELAM-1 was slightly increased in acute sympathetic
      ophthalmitis in comparison to fibrotic and normal eyes. VLA-6 was moderately
      increased in acute and fibrotic cases and VLA-2 VLA-3 and beta 3 were moderately
      expressed on all tissues examined. The differential expression of molecules known
      to be involved in lymphocyte activation and adhesion in acute sympathetic
      ophthalmitis suggests that certain adhesion molecules play a role in the
      pathogenesis of intraocular inflammation and may be suitable targets for
      immunotherapy.

PMID- 8293669
TI  - Binding sites of photoreceptor-specific antibodies COS-1, OS-2 and AO.
AB  - The chicken red-sensitive cone visual pigment (iodopsin) and several synthetic
      peptides of cone and rod visual pigments were used to find the binding sites of
      our photoreceptor-specific antibodies with immunocytochemistry. The ability of
      iodopsin to block immunolabeling with monoclonal antibodies COS-1 and OS-2
      furnished direct evidence that both antibodies are specific to visual pigments.
      Immunocytochemistry on whole-mount retinas with and without detergent, as well as
      electron microscopic labeling of cone photoreceptor membranes revealed the
      binding sites of COS-1 and OS-2 to be on the cytoplasmic side of the membrane. By
      testing several synthetic peptides, mainly from the C-terminal region of the cone
      visual pigments, we found that the domain consisting of the last 6 amino acids of
      the human red/green-, and the chicken red-sensitive cone pigments completely
      blocked immunolabeling with COS-1, while the sequence consisting of the last 12
      amino acids of the human blue cone pigment was effective to block the binding of
      OS-2. Both monoclonals can be regarded therefore C-terminal specific antibodies.
      OS-2 was found to bind to the dark-adapted photopigment more strongly than to the
      light-adapted one. The binding of the polyclonal rhodopsin antibody AO was almost
      entirely inhibited by the N-terminal synthetic peptide of bovine rhodopsin
      indicating that this antibody binds primarily to the N-terminal domain of
      rhodopsin in a tissue environment.

PMID- 8293670
TI  - Ocular renin angiotensin: EM immunocytochemical localization of prorenin.
AB  - Prorenin (PR) was localized by electron microscopic (EM) immunostaining of cryo
      ultramicrotomy sections of human ciliary body and correlated with light
      microscopic immunostaining. Both layers of the ciliary epithelium contained the
      prohormone. However, density was much higher in the adjacent extracellular
      spaces, particularly in the vitreous cortex. This observation adds further
      evidence to a role of the ciliary epithelium in the transfer, storage or
      synthesis of components of a putative ocular renin angiotensin system.

PMID- 8293672
TI  - Women in dermatology.

PMID- 8293671
TI  - Age-related changes in the molecular properties of vitreous collagen.
AB  - To understand the molecular events underlying rheological vitreous changes, age
      related changes in the molecular properties of bovine and human vitreous collagen
      were monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The
      adult bovine vitreous showed an increase in the high molecular-weight components
      of the collagen compared with the young samples. In addition, the apparent
      molecular size of the alpha-chain of the adult type II collagen was slightly
      larger than that of the young samples. The same tendency also was observed in
      human vitreous. The increase of high-molecular-weight components of the vitreous
      collagen could be attributed to intermolecular cross-links of the peptide chains.

PMID- 8293673
TI  - Contact allergens that pass through ordinary rubber gloves.

PMID- 8293674
TI  - A dermatologic diary. Portrait of a practice.

PMID- 8293675
TI  - Safety issues, risks, and precautions for dermatologic surgery.
AB  - The use of universal precautions can provide an effective barrier to transmission
      of viral infections. The most common route of occupational human immunodeficiency
      virus transmission to a health care provider is a self-inflicted needle stick
      with a contaminated needle. Use of the no-touch suturing technique in
      dermatologic surgery can lower the risk of such self-inflicted needle sticks.

PMID- 8293676
TI  - The status of women in dermatology.
AB  - In the near future, almost one-third of all American physicians will be women.
      Many of these women will be pressured by the needs to balance parental/family and
      professional responsibilities during the formative stages of their careers.
      Recommendations for medical school policy changes that recognize these pressures
      are made.

PMID- 8293677
TI  - Treatment of autoimmune blistering diseases.
AB  - This review highlights some of the recent advances and controversies in the
      treatment of autoimmune blistering diseases, with an emphasis on the practical
      management of these patients for the clinician. The indications, dosages, and
      side effects of drugs commonly used to treat these conditions are reviewed.
      Corticosteroids, administered either topically or systemically, are commonly used
      in the management of these disorders. Agents that may act as anti-inflammatory
      agents may offer some benefit, including gold, dapsone, antibiotics, and
      niacinamide. Immunosuppressants, particularly azathioprine or cyclophosphamide,
      are used as adjuvants in patients whose condition is not controlled on high
      dosage corticosteroids or who cannot tolerate the side effects of steroids.

PMID- 8293678
TI  - Cosmetic camouflaging techniques.
AB  - Cosmetic camouflaging techniques can be used to minimize the appearance of facial
      scarring due to trauma and/or surgery. Facial pigmentation defects are minimized
      through the application of facial foundations of complimentary colors. Principles
      of high-lighting and shadowing are used to conceal surface contour defects by
      combining opaque facial foundations with colored cosmetics.

PMID- 8293679
TI  - Advances in cryosurgery during the past decade.
AB  - Many advances have been made in cryosurgery during the past decade. Important
      considerations are the high cure rate, good cosmetic result, convenience, and
      cost effectiveness. In an era of budget restraints with regard to medical care
      and in a time of concern with exposure to bloodborne pathogens, cryosurgery
      offers unique solutions. Cure rates for skin cancer in the area of 97 to 98
      percent, for actinic keratosis, 98 percent, and for lentigo maligna, 96 percent,
      should encourage its use in more patients. The effectiveness in freezing lesions
      of leukoplakia, dermatofibroma, hemangioma, keloid, and lentigo adds to the
      versatility of the method. With the further development of ultrasound in
      measuring the depth of tumors prior to freezing and the availability of superior
      monitoring systems and perhaps helium cryosurgical units, cryosurgery could
      become the most widely used technique in dermatology. The development of a
      cryopeel for sundamaged skin provides an alternative treatment to the chemical
      peels in use today.

PMID- 8293680
TI  - Analysis of the influence of chromosomal condensation on the activity of
      restriction endonucleases.
AB  - The different responses of metaphase chromosomes to restriction endonuclease
      activity depend on the stage of chromosomal condensation. Results obtained
      established that this factor plays a remarkable role in obtaining high resolution
      banding patterns which facilitated visualization of a large number of sub-bands.
      It is evident that various restriction endonucleases, which are able to induce a
      coincident G-like banding pattern on Don cell line chromosomes, act in very
      different ways.

PMID- 8293681
TI  - Induction of DNA synthesis by microtubule depolymerization is mediated by actin
      filaments.
AB  - Colcemid (0.4 microgram/ml) induced DNA synthesis in quiescent chick embryo
      fibroblasts, and increased the amount of F-actin. Cytochalasin D, which
      disorganized actin filaments, inhibited the stimulation of DNA synthesis by
      colcemid. These results suggest that actin filaments are involved in the sequence
      of events leading from the depolymerization of microtubules to the initiation of
      DNA synthesis. They also demonstrate that depolymerization of microtubules can
      influence the amount of F-actin in the cell.

PMID- 8293682
TI  - Genetic recombination by spheroplast fusion in Escherichia coli K12.
AB  - Genetic transfer mediated by spheroplast formation and fusion in Escherichia coli
      was studied. Recombination did not occur from spheroplasts prepared by the
      combined glycine and lysozyme-EDTA treatment described by Coetzee et al. (1979).
      In contrast, when bacteria were exposed to a sub-inhibitory concentration of
      polymyxin B (0.5 microgram/ml) during the spheroplast generation phase,
      recombinants arose at frequencies of 1 x 10(-8) to 2.6 x 10(-8). The incidence of
      genetic transfer was further increased by adding 0.01 M CaCl2 to the polyethylene
      glycol fusion mixture (from 9 x 10(-7) to 9 x 10(-8). Finally, when the effects
      of both polymyxin B and calcium chloride were combined recombinants arose at
      frequencies of 3.4 x 10(-6) to 7.3 x 10(-7). These findings suggest that the
      detergent-like action of polymyxin B in removing a large part of the outer
      membrane enhances plasma membrane availability where fusion can take place.

PMID- 8293683
TI  - [The Chinese Journal of Obstetrics and gynecology 40th anniversary].

PMID- 8293684
TI  - [Women's health care in China].

PMID- 8293685
TI  - [Recent development of perinatal medicine in China].

PMID- 8293687
TI  - [Progress of gynecologic oncology in China].

PMID- 8293686
TI  - [Recent advances in reproductive endocrinology in China].

PMID- 8293688
TI  - [Recent advances of female contraception technology in China].

PMID- 8293689
TI  - [Progress in vitro fertilization research on mainland China].

PMID- 8293690
TI  - [Latest development on research of trophoblastic tumors].

PMID- 8293691
TI  - [40 years of the Chinese journal of obstetrics and gynecology].

PMID- 8293692
TI  - [Prevention of fetal growth retardation by low dose aspirin].
AB  - A prospective randomized, double-blinded, controlled clinical trial was conducted
      in 84 pregnant women with high risk of intrauterine growth retardation (IUGR).
      From the 28th to 30th week of gestation, low dose aspirin 75 mg/day (study group,
      n = 40) or placebo (control group, n = 44) was given consecutively for 6 to 8
      weeks. It was found that the mean value of systolic/diastolic ratio of umbilical
      artery flow velocity waveforms in the study group was significantly lower than
      that of the control group after drug use. The occurrences of IUGR and
      preeclampsia in the study group (7.5% and 10.0% respectively) were remarkably
      lower than those in the control group (27.3% of both). The adverse effects of low
      dose aspirin on both mother and fetus were not observed. These results suggest
      that low dose aspirin administration (75 mg/day) beginning at earlier stage of
      third trimester may improve the fetal placental circulation, and thus prevent
      IUGR and/or preeclampsia effectively.

PMID- 8293693
TI  - [The frequencies of sister chromatid exchanges and chromosomal aberrations in the
      peripheral lymphocytes in patients with cervical carcinoma].
AB  - The study of the SCE frequencies and chromosome aberrations in 20 patients with
      cervical carcinoma and 20 cases of healthy women was carried out. The result
      showed that the SCE frequencies were as high as 9.28 +/- 0.34/cell in the
      patients with cervical cancer. They were significantly higher than those of the
      normal control group (P < 0.001). The chromosomal numerical changes and
      structural aberrations of the patients were much more than those of the normal
      women (P < 0.01). The important structural aberrations included ring chromosome,
      chromosomal restituation and breakage. Genetic instability and DNA repair level
      significantly suppressed in cancer patients were detected.

PMID- 8293694
TI  - [Therapy of borderline ovarian tumors].

PMID- 8293695
TI  - The risks and uses of donated blood.

PMID- 8293696
TI  - Ambisome--liposomal amphotericin B.

PMID- 8293697
TI  - Nicotine patches.

PMID- 8293698
TI  - Nutritional status of urban Nigerian school children relative to the NCHS
      reference population.
AB  - The present study assessed the growth problems in an indigenous African
      population of Nigerian urban public school children. The study population
      consisted of 1390 Nigerian children (predominantly Igbo), 718 boys and 672 girls,
      ages 4-10 years. Compared to the National Center for Health Statistics (NCHS)
      reference population, the Nigerian children had an excess prevalence of both
      short stature and underweight. The prevalence of short stature was 14.2% for the
      boys and 17.4% for the girls. Approximately 20% of the children were underweight
      whereas less than 1% were considered overweight. These data demonstrate an excess
      of both acute and chronic malnutrition relative to the NCHS reference population.

PMID- 8293699
TI  - HIV infection among secondary school students in Djibouti, horn of Africa:
      knowledge, exposure and prevalence.
AB  - A study of HIV infection among secondary school students was conducted in
      Djibouti in February 1990 during a national hepatitis survey. Serology was
      negative for HIV and syphilis among 294 students (ages 14 to 20 years) in spite
      of a dramatic increase of HIV seropositivity (as high as 41%), and a high level
      of syphilis positive serology (up to 46%) among adult high-risk groups such as
      street prostitutes. Results of a face-to-face interview of these pupils indicated
      that 64% had a basic knowledge of AIDS. As expected, a much better knowledge of
      AIDS was found among those who recently received AIDS education. However, 80% of
      secondary school teenagers did not consider themselves at risk for acquiring HIV.
      Transmission of HIV among school-children would be possible through sexual
      activity (22% stated to be sexually active) or parenteral therapy (75% had
      received at least one intramuscular injection), and not likely through blood
      transfusion or intravenous drug abuse. Results, close to those of a similar study
      in Zimbabwe, suggest that AIDS education programme should be given to all
      secondary school pupils and include public health lectures on syphilis,
      tuberculosis, and HIV infection.

PMID- 8293700
TI  - Clinical trial of riboflavin in sickle cell disease.
AB  - The effect of riboflavin supplementation (5mg twice daily for 8 weeks) on reduced
      blood glutathione (GSH) and iron status was assessed in 18 patients with sickle
      cell disease (SCD-HbSS). Twelve SCD patients and 13 normal (Hb-AA) subjects
      served as the control. The total iron binding capacity (TIBC) and serum ferritin
      (SF) were significantly higher (p < 0.01), but GSH level, haemoglobin and
      transferrin saturation (TS) were significantly lower (p < 0.001) in SCD patients
      than in normal subjects. The administration of riboflavin elicited a significant
      increase (p < 0.01) in serum iron and TS but a non significant increase in SF and
      circulating Hb. The GSH level varied little in riboflavin supplemented but
      decreased significantly in unsupplemented SCD. The disparity in GSH concentration
      might reflect availability of FAD for regeneration of GSH from glutathione.
      Likewise, the haematological improvement in the supplemented group supports the
      assertion that riboflavin enhances erythropoiesis. For an effective management of
      SCD in Africa, a closer attention should be directed to the riboflavin status in
      haemolytic disorders.

PMID- 8293701
TI  - Asphyxia of the newborn in east, central and southern Africa.
AB  - Very scanty information is available in East, Central and Southern Africa on the
      incidence and risk factors associated with asphyxia of the newborn. A multicentre
      prospective study involving 4267 deliveries in eight countries was undertaken
      over a three month period, in maternity units of the central hospitals to
      determine the incidence; maternal, service and logistic risk factors for asphyxia
      of the newborn as determined by an abnormally low apgar score. 30% of births were
      by primigravida mothers, of whom 67% were teenagers. A birth by a teenager had a
      higher risk for low birth weight. Overall incidence of low birth weight was
      13.9%. The overall incidence of asphyxia of the newborn was 22.9% while that
      associated with low birth weight (i.e. babies weighing less than 2500 grams) was
      29.3% compared with 21.5% among the normal birth weight babies. Low birth weight
      contributed a large proportion of the high neonatal mortality of 15.9% compared
      to 1.8% for normal birth weight babies by 24 hours after birth. The mean
      mortality by 24 hours post delivery was 3.8%. Obstetrical complications are
      important risk factors for asphyxia of the newborn. Among the important risk
      factors are those associated with prolonged labour and intra partum accidents.
      The incidence of risk for asphyxia broadly was 21.3%, which is very close to the
      actual incidence of asphyxia of 22%. Lack of referral contributed to increased
      risk of asphyxia. In a significant proportion of infants, resuscitation measures
      taken were inappropriate. The stillbirth rate was 3.0% while the incidence of
      externally evident congenital malformations was 1.2%. There is urgent need to
      institute appropriate measures to prevent and manage asphyxia of the newborn in
      the region. These should include identification of the at risk mother, proper
      referral and management while adhering to correct established procedures. There
      is also need to develop appropriate and relevant technologies for perinatal and
      neonatal care through research undertaken in the region. It is also concluded
      that the co-operation and joint effort between the obstetricians, paediatricians
      and the nursing staff who all contributed to the collection of this data is a
      cost effective approach to research in perinatal health and consequently in
      instituting interventions.

PMID- 8293702
TI  - Epidemiological factors associated with neonatal tetanus mortality: observations
      from a cluster survey in Nigeria.
AB  - A cluster survey on neonatal tetanus (NNT) mortality was conducted in Kano
      Metropolis, Northern Nigeria, to investigate epidemiological factors associated
      with NNT mortality. The survey was a two-stage cluster sampling technique and
      lasted for two weeks. A total of 2,623 live-births were recorded over a 12-month
      period. Less than 40% of the births followed two or more antenatal visits and
      tetanus toxoid coverage was 32.0%. Over 60% of births were outside hospitals and
      related facilities. Of the epidemiological factors investigated, only antenatal
      care, tetanus toxoid coverage, hospital delivery, poor cord management and
      traditional surgery showed significant association with NNT death. It is
      suggested that an appropriate community-specific prevention strategy for the
      region should include health education to improve utilisation of antenatal and
      hospital-delivery facilities, discourage traditional surgery and improve tetanus
      toxoid coverage. A case is also made for training and involvement of traditional
      birth attendants (TBAs) since most deliveries occurred outside hospitals and
      related facilities.

PMID- 8293703
TI  - Birth trauma among liveborn infants in Mulago Hospital, Uganda.
AB  - In this retrospective review, data is presented of birth trauma seen among 4288
      live born infants admitted to the special care unit of a large hospital over a
      three year period. Hypoxaemic brain injury resulting from birth asphyxia was by
      far the commonest form of birth trauma in this sample and it was the main cause
      of death, in many infants. All infants diagnosed as having sustained intracranial
      haemorrhage died while none of the other types of birth injuries were associated
      with any deaths. The need is emphasised to handle "high risk" deliveries with
      extra care while at the same time seeking solutions to the risk factors as well
      as lifting the overall standard of living of women in the community.

PMID- 8293704
TI  - Copper, zinc and superoxide dismutase activities in premature infants: a review.

PMID- 8293705
TI  - The relationship between tooth brushing frequency and personal hygiene habits in
      teenagers.
AB  - A survey of 904, 14-17 year old school children from secondary schools around
      Nairobi was done to find out if there was any relationship between toothbrushing
      frequency and personal hygiene habits. The students completed a questionnaire
      anonymously in class. Female students brushed their teeth more often than the
      male students. 62.2% of the females and 50.1% of the males brushed their teeth
      more than once a day. Of those students who brushed their teeth more than once a
      day, 52% bathed daily, 22% used perfumes/deodorants daily and 50.1% always washed
      their hands after visiting the lavatory. No relationship was found between
      washing of hair and toothbrushing frequency. 69.7% males and 53.2% females gave
      toothache and tooth decay as the main reasons for mouth care. Those who brushed
      their teeth more frequently also visited the medical doctor regularly for routine
      check-ups. These findings indicated that toothbrushing was closely related to
      personal hygiene habits.

PMID- 8293706
TI  - The limitations of ultrasonography in the management of testicular abscesses.
AB  - Preoperative ultrasound images of 12 cases of testicular abscess were correlated
      with the clinical, operative and pathological diagnosis. No ultrasonic appearance
      was consistent enough to permit a confident diagnosis of abscess formation.

PMID- 8293707
TI  - Radiological observations in the colon of Nigerians with chronic enema abuse.
AB  - Barium enema examination performed on the indigenes of Calabar community (the
      Efiks) demonstrated redundancy (dolichocolon) in various segments of the colon in
      a high proportion (71%) of habitual enema abusers compared to non-abusers (19%).
      Comparatively, the descending colon appeared the most vulnerable segment of the
      gut. The typical features of enema colitis was not found in any of the subjects
      probably because of the non-corrosive nature of the concoctions they used in
      clearing their gut. It is concluded that prolonged stimulation of the colon with
      enema together with the instruments used to deliver the concoction results in the
      redundancy. To enhance accurate radiological evaluation of colonic lesions
      amongst Nigerians of Efik origin, chronic enema abuse should be considered.

PMID- 8293708
TI  - Measles in Mashonaland Central Province: Zimbabwe.
AB  - A review of measles notifications in Mashonaland Central Province, Zimbabwe from
      1st September 1987 to 31st October 1989 was done. Data reviewed were from monthly
      maternal and child health summary forms and from hospital in-patients disease
      statistics. There was an increase in the incidence of measles first towards the
      end of 1987 and secondly after August 1988. The overall case fatality rate (CFR)
      for in-patients was 2.0%, with 2 peaks in CFR. The second peak of CFR coincided
      with the peak of the epidemic in December 1988. CFR was highest in infancy,
      intermediate in the 1 to 4 year age group and least for older children (above 5
      years). The highest age specific attack rate was observed in infancy. The
      efficacy of the measles vaccine (Schwartz freeze dried measles vaccine given as a
      single dose at 9 months) was estimated to be 84.9% A large pool of susceptibles
      who possibly maintained the epidemic include an accumulation of unimmunised
      children and adults. Despite a measles immunisation coverage rate of 67.6% for
      Mashonaland Central Province in 1988, a sustained effort to maintain and increase
      immunisation coverage is vital to contain measles together with other EPI target
      diseases.

PMID- 8293709
TI  - Primary malignant fibrous histiocytoma of the mandible: a case report.
AB  - A case report of a primary malignant fibrous histiocytoma (MFH) in the mandible
      of a young adult male is presented and relevant literature reviewed. The clinical
      presentation and course of the case is typical of MFH of the jaw as reported in
      the literature.

PMID- 8293710
TI  - Oropharyngeal teratoma in a child: a case report.
AB  - Teratoid tumours of the oropharynx are notorious for obstructing the airways and
      interfering with alimentation. We report here a healthy 20-day old neonate who
      presented with a painless growth in the floor of the mouth from birth. In this
      neonate, the tumour interfered with breast-feeding but not with bottle-feeding
      which the child tolerated very well. At operation, the tumour was easily
      enucleated, weighed 6G and was histologically consistent with a teratoma. The
      commonest site for this tumour is the nasopharynx and only 26 oropharyngeal
      teratomas have been reported in the English literature. The differential
      diagnosis of congenital oral growths should include a teratoma.

PMID- 8293711
TI  - Giemsa and acridine orange stains: a laboratory experience in the diagnosis of
      leishmaniasis--short communication.

PMID- 8293712
TI  - Patent ductus arteriosus in the preterm infant.

PMID- 8293713
TI  - Spectral analysis of antepartum fetal heart rate variability from fetal
      magnetocardiogram recordings.
AB  - Fetal heart rate variability was derived from fetal magnetocardiogram recordings
      in ten subjects at gestation ages 32-38 weeks. Maternal interference was
      negligible and R-wave detection was highly reliable. Oscillations suggestive of
      respiratory sinus arrhythmia (RSA) were prominent in many of the heart rate
      tracings. Spectral analysis was used to quantify heart rate variability and to
      examine the influence of the RSA-like oscillations on heart rate variability. The
      oscillations were associated with increased power in the frequency range 0.4-1.0
      Hz (P < or = 0.05). Magnetic recording appears to offer significant advantages
      for investigation of beat-to-beat fetal heart rate throughout the latter stages
      of pregnancy.

PMID- 8293714
TI  - Arterial blood pressure and blood flow velocity in major cerebral and visceral
      arteries. II. Effects of colloid infusion.
AB  - To compare the effects of acute changes in blood pressure on arterial blood flow
      velocity in various regional circulations, Doppler ultrasound measurements of
      blood flow velocity were recorded from the anterior cerebral artery (ACA),
      superior mesenteric artery, coeliac axis and left renal artery. Measurements were
      obtained from 10 ventilated very low birth weight infants before and after plasma
      infusions given to treat systemic hypotension on the first day of postnatal life.
      Blood pressure increased in 8/10 infants, and in this group there was a
      significant increase in ACA and coeliac axis blood flow velocity. For the ACA
      only, there was a significant association between the change in blood flow
      velocity and the magnitude of the change in blood pressure (r = 0.73, P < 0.02).
      Mesenteric and renal artery velocity did not increase after the infusion. For
      ventilated VLBW infants on the first day of life, arterial blood flow velocity
      was affected by acute changes in blood pressure in the cerebral circulation only.

PMID- 8293715
TI  - The relationship of plasma cholecystokinin levels to different feeding routines
      in newborn infants.
AB  - Plasma cholecystokinin concentrations were measured with radioimmunoassay in
      breast fed infants in Sweden (n = 101) and formula fed infants in Italy (n =
      119). Blood samples were collected from the infants during the first five
      postnatal days, just before feeding in a cross-sectional way. We found no
      significant difference in the hormone concentration in relation to age, in breast
      fed or in formula fed infants. Breast fed infants had significantly higher plasma
      hormone concentrations than formula fed infants during the postnatal period 0-5
      days: 2.8 pmol/l (1-10 pmol/l), median (range) versus 2.2 pmol/l (1-25 pmol/l),
      (P < 0.02). It cannot be excluded that the results were influenced by the
      circumstances that the samples were collected from two separate populations.
      However, the higher hormone levels in breast fed infants may also be the
      expression of the fact that natural feeding per se promotes cholecystokinin
      secretion in newborn infants.

PMID- 8293716
TI  - Neonatal morphometric indices of fetal growth: analysis of observer variability.
AB  - Measurements of triceps and subscapular skinfold thickness, mid-arm circumference
      (MAC), head circumference (HC) and crown-heel length were performed by two
      observers in 30 healthy neonates. Intra-observer standard deviation for all
      measurements, calculated using one-way analysis of variance, was small and
      similar for each observer. Inter-observer variability was assessed using limits
      of agreement. There were small, systematic, differences between observers for
      measurements of triceps skinfold thickness and crown-heel length, and for
      calculated ponderal index (PI). When related to respective published reference
      ranges, the 95% prediction intervals for subscapular (-0.51, 0.68 mm) and triceps
      (-0.65, 0.29 mm) skinfold thicknesses were less than those for the MAC/HC ratio (
      2.1, 1.9) and PI (-0.23, 0.28). The results indicate that skinfold thickness
      measurements are a more robust measure and, therefore, may be of greater value in
      the assessment of neonates with suspected fetal growth retardation.

PMID- 8293717
TI  - Severity of abruptio placentae and neurodevelopmental outcome in low birth weight
      infants.
AB  - The short term neonatal morbidity and 2-year neurodevelopmental outcome were
      evaluated in 40 low birthweight (< 2500 g) liveborn infants delivered after
      abruptio placentae and in 80 control infants of similar gestational age. Apgar
      scores at 1' and 5' were lower in infants born to mothers with severe abruption.
      The prevalence of intraventricular hemorrhage (Grades I-IV) was 17.5% (7/40) in
      the cases and 5% (4/80) in the controls (P = 0.035). Cystic periventricular
      leukomalacia was diagnosed in two cases (5%) and in none of the controls (P =
      0.1). At 2-year follow-up, among surviving infants, cerebral palsy (spastic
      diplegia, hemiplegia or tetraplegia with or without mental retardation) was
      diagnosed in 11.1% (4/36) of the cases and in none of the 76 controls (P =
      0.011). After adjustment by logistic regression analysis for the effect of
      confounders (gestational age, birthweight, social class and duration of mother's
      education) the odds ratio of a poor outcome defined as neonatal death or cerebral
      palsy was 4.4 (95% confidence interval, 1.2-17.0) in index cases as a whole and
      8.0 (95% confidence interval, 1.5 to 43.0) in the subgroup of infants born after
      severe abruption. Mild abruption did not affect the 2-year infant outcome in both
      univariate and multivariate analysis.

PMID- 8293718
TI  - Conservative management of foetal lung lesions.
AB  - Routine antenatal ultrasound screening has identified a variety of malformations
      which may present as hyperechogenic or cystic lung lesions. Knowledge of the
      natural history of these lesions in utero and after birth is incomplete, and an
      exact diagnosis is not always possible. Despite this, an increasing number of
      interventions and terminations of pregnancy are being undertaken. We advocate a
      more conservative approach in the management of these lesions. We describe three
      cases and review the current literature to demonstrate the uncertain natural
      history of these lesions, the diagnostic difficulties, and some of the medical
      and ethical problems of intervention.

PMID- 8293719
TI  - The effect of behavioural state on general movements in healthy full-term
      newborns. A polymyographic study.
AB  - In a group a eight healthy full-term newborns 6-h polygraphic recordings, which
      included EMG recording of eight arm muscles, were made to investigate the effect
      of behavioural state on general movement (GM) organization. Simultaneous video
      recordings supplied information about the form of the GMs. Additionally the
      effect of non-nutritive sucking during State 4 was evaluated. Behavioural state
      had a distinct effect on the makeup of GMs. GMs during State 4 displayed best the
      fluency and elegance which are characteristic of normal GMs. State-1-GMs were
      rare, had a short duration and sometimes had an abrupt onset. During State 2 GMs
      had a fragmented appearance. EMG differences between GMs in State 2 and State 4
      were demonstrated in burst duration (longer during State 2) and tonic background
      activity in the upper arm muscles (lower during State 2). Occasionally State-2
      GMs had an abrupt onset. These abrupt GMs were less often preceded by rapid eye
      movements and heart rate changes than State-2-GMs with a gradual onset. GMs
      during State 5 were abrupt and vigorous and often had a high frequency tremor
      superimposed. The EMGs of State-5-GMs revealed a shorter interval between the EMG
      bursts and a higher EMG burst amplitude in the upper arm muscles than present
      during State-4-GMs. Non-nutritive sucking during State 4 induced a reduction of
      movement amplitude, a increase of EMG burst duration and an increase of tonic
      background activity in the biceps brachii and the extensor carpi muscles.

PMID- 8293720
TI  - Major patterns of human inheritance: relevance to the epilepsies.
AB  - An understanding of the basic principles of human inheritance patterns is
      necessary to appreciate the variety and complexity of genetic influences in the
      epilepsies. The various modes of human inheritance include single gene
      (mendelian), chromosomal, mitochondrial, and multifactorial/polygenic. Recent
      insights regarding imprinting, anticipation, and uniparental disomy have been
      made and have an impact on our understanding of human genetics. All of these
      phenomena are likely to be of importance in the epilepsies and form the basis for
      a more detailed analysis of the relevant molecular biology.

PMID- 8293721
TI  - Complex genetic disease: can genetic strategies in Alzheimer's disease and new
      genetic mechanisms be applied to epilepsy?
AB  - Strategies used in molecular genetics have changed modern neurology. The gene or
      genes responsible for several major neurologic diseases have now been identified
      using "reverse" or positional genetics. Unexpected new genetic mechanisms have
      been discovered in human neurologic diseases, including (a) identical mutations
      of the prion protein gene in Creutzfeldt-Jakob disease and fatal familial
      insomnia with the phenotypic expression directed by an accompanying polymorphism;
      (b) stable duplications of chromosome 17 in Charcot-Marie-Tooth disease (type 1A)
      that involve many genes, only one of which appears to cause neuropathy; and (c)
      highly variable, dynamic mutations in myotonic dystrophy, fragile X syndrome, and
      Kennedy's syndrome that modulate variable expressivity in multiple tissues. There
      is growing recognition that neurologic diseases are often complex genetic
      diseases with multifactorial rather than simple modes of inheritance. For
      example, genetic association/linkage strategies have interacted with biochemistry
      and immunopathology studies to produce new insights into the disease mechanism of
      late-onset Alzheimer's disease. The role of apolipoprotein E in late-onset
      Alzheimer's disease is an example of how new analytical techniques of genetic
      disease can be applied to dissect multiple genes. Similar research strategies are
      suggested for the study of epilepsy as a complex disease.

PMID- 8293722
TI  - Progress in mapping human epilepsy genes.
AB  - The chromosomal loci for seven epilepsy genes have been identified in chromosomes
      1q, 6p, 8q, 16p, 20q, 21q, and 22q. In 1987, the first epilepsy locus was mapped
      in a common benign idiopathic generalized epilepsy syndrome, juvenile myoclonic
      epilepsy (JME). Properdin factor or Bf, human leukocyte antigen (HLA), and DNA
      markers in the HLA-DQ region were genetically linked to JME and the locus, named
      EJM1, was assigned to the short arm of chromosome 6. Our latest studies, as well
      as those by Whitehouse et al., show that not all families with JME have their
      genetic locus in chromosome 6p, and that childhood absence epilepsy does not map
      to the same EJM1 locus. Recent results, therefore, favor genetic heterogeneity
      for JME and for the common idiopathic generalized epilepsies. Heterogeneity also
      exists in benign familial neonatal convulsions, a rare form of idiopathic
      generalized epilepsy. Two loci are now recognized; one in chromosome 20q (EBN1)
      and another in chromosome 8q. Heterogeneity also exists for the broad group of
      debilitating and often fatal progressive myoclonus epilepsies (PME). The gene
      locus (EPM1) for both the Baltic and Mediterranean types of PME or Unverricht
      Lundborg disease is the same and is located in the long arm of chromosome 21.
      Lafora type of PME does not map to the same EPM1 locus in chromosome 21. PME can
      be caused by the juvenile type of Gaucher's disease, which maps to chromosome 1q,
      by the juvenile type of neuronal ceroid lipofuscinoses (CLN3), which maps to
      chromosome 16p, and by the "cherry-red-spot-myoclonus" syndrome of Guazzi or
      sialidosis type I, which has been localized to chromosome 10. A point mutation in
      the mitochondrial tRNA(Lys) coding gene can also cause PME in children and adults
      (MERFF).

PMID- 8293723
TI  - Mitochondrial DNA mutations in epilepsy and neurological disease.
AB  - Recent discoveries in mitochondrial clinical genetics have revealed that a broad
      spectrum of clinical phenotypes are associated with mutations in mitochondrial
      DNA. Diseases caused by mutations in mitochondrial DNA are by nature
      quantitative. Myoclonic epilepsy and ragged-red fiber disease are caused by a
      mutation in the transfer RNA gene lysine. Although everyone in a maternal lineage
      will harbor the same mutation, the nature and severity of the symptoms vary
      markedly among individuals. This variability correlates with the inherited
      percentage of mutations in the individual's mitochondrial DNA and the
      individual's age. Age-related expression of mitochondrial disease has also been
      demonstrated for mitochondrial DNA deletions. Although deletions that retain both
      origins of replication result in late-onset disease because of the progressive
      enrichment of the deleted mitochondrial DNA, a 10.4-kb deletion that lacks the
      light-strand replication origin and maintains a stable mutant percentage in both
      tissues and cultured cells has been discovered. This deletion is associated with
      adult-onset diabetes and deafness, but not with ophthalmoplegia, ptosis, or
      mitochondrial myopathy. Biochemically, it causes a generalized defect in
      mitochondrial protein synthesis and oxidative phosphorylation. The age-related
      decline in oxidative phosphorylation could reflect the accumulation of somatic
      mitochondrial DNA mutations. Inhibition of oxidative phosphorylation stimulates
      this accumulation. The general paradigm for mitochondrial DNA diseases may be
      that inherited mutations inhibit the electron transport chain. This damages the
      mitochondrial DNA, further reducing oxidative phosphorylation. Ultimately,
      oxidative phosphorylation drops below the expression threshold of cells and
      tissues, and clinical symptoms appear.

PMID- 8293724
TI  - Identification of genetic defect of an epilepsy: strategies for therapeutic
      advances.
AB  - Advances in molecular genetics and molecular biology are transforming the biology
      of human disease. Cures for diseases previously refractory to all treatments have
      become the reality for some disorders and the legitimate promise for others. In
      the case of the epilepsies, identification of mutant genes underlying familial
      epilepsies may lead to a new pharmacology, through the development of in vitro
      expression systems permitting rapid search for novel drugs, creation of highly
      specific animal models based on expression of the precise mutation, and
      correction of disease phenotype by introducing novel and highly specific genetic
      information into the person with epilepsy.

PMID- 8293725
TI  - Basic concepts of molecular biology for the epileptologist.
AB  - Fundamental techniques used in molecular biology can be applied toward questions
      of relevance to epilepsy. Many of the most common techniques used for working
      with nucleic acids, including DNA extraction, electrophoresis, cloning in plasmid
      vectors, making probes, and the polymerase chain reaction are now commonly used
      in basic epilepsy research. Some specific approaches that can be used to address
      particular questions are methods for identifying a human gene (Southern analysis
      and screening a library), determining whether a gene is expressed in a given
      brain region (Northern analysis and in situ hybridization), and expressing a gene
      in tissue culture or a whole organism (cell transfection and transgenic animals).

PMID- 8293726
TI  - Stress and the memory T-cell response to the Epstein-Barr virus in healthy
      medical students.
AB  - This study investigated the memory T-cell proliferative response to several early
      and late Epstein-Barr virus (EBV) polypeptides. Blood samples were collected
      twice, 1 month before a 3-day block of examinations and again on the last day of
      the exam series. Ss were 25 healthy, EBV seropositive medical students. The
      proliferative response to 5 of the 6 EBV polypeptides significantly decreased
      during examinations. In addition, Ss high (above the median) in seeking support,
      as measured by the COPE, had lower proliferative responses to 3 EBV polypeptides
      (p17, p52/50, and p85), as well as higher levels of antibody to EBV virus capsid
      antigen. The data provide further evidence that psychological stress can modulate
      the cellular immune response to latent EBV.

PMID- 8293727
TI  - Cigarette smoking under stress: the role of coping expectancies among smokers in
      a clinic-based smoking cessation program.
AB  - This study examined 2 expectancies to explain smoking under stress: smokers'
      expectations about their ability to cope with stress while remaining abstinent
      and their expectations about the stress-ameliorating and coping benefits of
      smoking under stress. The interaction of the expectancies concurrently predicted
      smoking urge under stress, which, in turn, predicted subsequent smoking. The
      interaction of posttreatment expectancies prospectively predicted smoking status
      3 months after treatment, although the coping benefits of smoking expectancy
      effect was reversed. Expectations about coping ability increased and expectations
      about the coping benefits of smoking decreased as a function of participating in
      a smoking cessation program. The discrepant concurrent and prospective findings,
      reasons that coping expectancies are associated with smoking under stress, and
      treatment implications are discussed.

PMID- 8293728
TI  - Cardiovascular reactivity as a predictor of relapse in male and female smokers.
AB  - This study examined the role of psychophysiological reactivity to general
      stressors measured before smoking cessation as a predictor of relapse in
      individuals who quit for a minimum of 12 hr and were then followed for a 12-month
      interval. The study group consisted of 132 (56.9%) female and 100 (43.1%) male
      participants in a formal smoking cessation program. The reactivity measures were
      taken while the Ss were still smoking. Heart rate and blood pressure measurements
      were taken while Ss were resting, performing mental arithmetic, and delivering a
      speech and after Ss had been standing for 2 min. In the sample as a whole and for
      women, a higher level of systolic blood pressure reactivity to the cognitive
      challenge was associated with a shorter time to relapse (p < .05). In men,
      greater systolic blood pressure decline to standing was significantly associated
      with a shorter time to relapse (p < .05).

PMID- 8293729
TI  - Cardiovascular and emotional responses in women: the role of hostility and
      harassment.
AB  - The relation of hostility and harassment to cardiovascular and emotional
      responses was examined by having 51 women (ages 18-26) high and low in hostility
      complete a task with or without harassment. Harassed high hostile Ss showed
      greater systolic blood pressure (SBP) increases during task and recovery periods
      than did harassed low hostile Ss and nonharassed Ss. Harassed low hostile Ss
      evidenced greater SBP increases during task and recovery periods than did
      nonharassed Ss. Among high hostile women, cardiovascular elevations during the
      task were associated with self-reported levels of negative affect. Antagonistic
      hostility, relative to neurotic hostility, was positively associated with
      harassment-induced SBP changes. These results support the hypothesis that hostile
      people exhibit excessive behaviorally induced cardiovascular responses to
      interpersonally challenging tasks that evoke anger-related emotional states.

PMID- 8293730
TI  - Anticipatory anxiety in women receiving chemotherapy for breast cancer.
AB  - This study examined (a) the prevalence and course of anxiety before the 1st 6
      infusions of cancer chemotherapy and (b) the contribution of trait anxiety, side
      effect expectations, and prior occurrence of posttreatment side effects to
      anxiety before infusions. Fifty-three women receiving adjuvant chemotherapy for
      breast cancer participated. Anxiety was most prevalent and intense before the 1st
      infusion. Trait anxiety predicted anxiety before both the 1st and subsequent
      infusions. Prior occurrence of posttreatment nervousness also predicted anxiety
      before subsequent infusions, even after accounting for trait anxiety and other
      posttreatment side effects. Results are discussed in terms of the role that
      anxiety proneness, response expectancy, and classical conditioning may play in
      the development of anxiety before repeated chemotherapy infusions.

PMID- 8293731
TI  - Attitudes, knowledge, and stages of change: a survey of exercise patterns in
      older Australian women.
AB  - This article describes a telephone survey of attitudes and behavior relevant to
      exercise adoption among 286 Australian women aged 50 to 64. Stages of change
      identified by the transtheoretical model of behavior change were related to
      attitudes, knowledge, and demographic variables. In comparison with exercisers,
      precontemplators were older, had lower exercise knowledge, perceived lower levels
      of family support for exercise, expected fewer psychological benefits from
      exercise, and rated exercise as less important than avoiding smoking. The main
      significant difference between contemplators and those in the action or
      maintenance stage involved the perception of practical barriers. Despite the
      limitations of this cross-sectional self-report study, it identifies attitudes
      and knowledge as potential targets for intervention with middle-aged women.

PMID- 8293732
TI  - Safer sex knowledge, behavior, and attitudes of inner-city women.
AB  - Sexual behavior, knowledge of HIV transmission and prevention, perceived risk of
      AIDS, and safer sex behavior were studied in a sample of 289 single, pregnant,
      inner-city women. African-American and European-American women were equally
      represented. Women had poor AIDS knowledge. Sexual behavior placed women at risk
      for HIV infection due to the lack of condom or spermicide use. Women did not
      perceive themselves at risk for the AIDS virus, although they did recognize that
      heterosexuals were at risk. Their lack of risk perception was partly based on
      their having a single sexual partner. They did not regard their partner's current
      or past behavior as placing them at risk. Recommendations for intervention and
      cultural differences were discussed.

PMID- 8293733
TI  - Self-perception variables that mediate AIDS-preventive behavior in college
      students.
AB  - Three psychological variables--self-efficacy, control and meaning, and perceived
      risk--were tested in a structural model predicting AIDS-preventive behavior.
      Results revealed a good model fit, indicating that these psychological variables
      did play a role in mediating AIDS-preventive behavior in college students. A
      multivariate analysis of variance and individual analyses of variance conducted
      for men and women also revealed gender differences on individual items of self
      efficacy, perceived risk, and AIDS-preventive behavior. This study underscores
      the importance of identifying and assessing the psychological determinants of
      AIDS-preventive behavior.

PMID- 8293734
TI  - Effects of tobacco abstinence on food intake among cigarette smokers.
AB  - The total caloric and specific nutrient intakes of smokers who became abstinent
      were compared with those of a control group. Both groups were composed of
      volunteer inpatients housed in a research ward for 7 days. After smoking ad
      libitum for 3 days, the experimental group was required to abstain from tobacco
      for the next 4 days while the control group continued to smoke. Significant
      increases in total caloric intake and in grams of carbohydrates, protein, fat,
      and sucrose were observed in the experimental relative to the control group,
      whereas no significant differences were found in fructose intake. The increase in
      caloric intake was not specific to increases in snacking. Preliminary analyses
      showed gender differences in food intake as a result of tobacco abstinence.

PMID- 8293735
TI  - Psychological minimization of cholesterol test results: moderators of appraisal
      in college students and community residents.
AB  - College students received randomly assigned desirable or borderline-high
      cholesterol test results. Borderline-high Ss rated high cholesterol as a less
      serious threat to health, viewed the test as less accurate, and perceived high
      cholesterol as more common than did those given desirable readings. High self
      esteem or blunting coping style predicted lower distress after borderline-high
      readings but did not moderate cognitive appraisal. In Study 2, minimization was
      again observed among participants in a community screening, primarily among those
      who had never been tested. Although the never-tested group was younger and less
      knowledgeable about cholesterol, these factors did not account for minimization.
      The results support the generalizability of laboratory data on risk appraisal and
      provide new evidence regarding the nature and determinants of threat
      minimization.

PMID- 8293736
TI  - Magnetic resonance imaging of muscles in myotonic dystrophy.
AB  - The MR findings in 27 patients with myotonic dystrophy were compared with those
      observed in 11 patients with other muscular dystrophies: six with limb-girdle
      dystrophy, three with facioscapulohumeral muscular dystrophy and two with Becker
      type muscular dystrophy. Clinical status was graded into 10 stages. The MR study
      was performed at the medium third of the thigh, with a slice thickness of 7.5 mm
      (TR: 750/TE: 25 for T1; TR: 2200/TE: 30/90 for DP/T2). Muscle signal intensity
      was evaluated with a four-point grading scale using subcutaneous fat as a
      reference. Statistical analysis was done using the Mann-Whitney-Wilcoxon's test
      and simple linear regression. In the myotonic dystrophy group, 81.4% of the
      patients showed an abnormal signal at the crural muscle level, adopting a
      semilunar shape around the anteroexternal side of the femur. The presence and
      intensity of this hyperintense signal correlated positively with the duration of
      disease (r = 0.54) and the clinical stage (r = 0.69). Of the 11 patients with
      other muscular dystrophies, only three (27.2%) showed hyperintense signal at the
      crural muscle level. MR imaging of patients with muscle disease may contribute to
      the in vivo study of muscular dystrophy, its differential diagnosis and the
      detection of asymptomatic patients.

PMID- 8293737
TI  - Value of MR imaging in middle fossa arachnoid cyst with intracystic and subdural
      hematoma.

PMID- 8293738
TI  - Magnetic resonance imaging of calcified thoracic disk herniation.

PMID- 8293739
TI  - Quantification of occlusive and reperfused myocardial infarct size with Gd-DTPA
      enhanced MR imaging.
AB  - The potential of Gd-DTPA-enhanced magnetic resonance imaging (MRI) for measuring
      infarct size was assessed in canine hearts. Twelve dogs underwent pre- and post
      contrast MR imaging before and after recanalization. Infarct area was identified
      by triphenyltetrazolium chloride (TTC) staining of postmortal specimens in each
      case. Recanalization was complete in 10 dogs. High SI area was seen after
      reperfusion in nine of them; and it showed low signal intensity before
      reperfusion in seven of them. Two dogs were killed during reperfusion period:
      neither of them showed a low SI area before reperfusion. Necrotic regions were
      confirmed by TTC staining in seven of 12 dogs. Both the visual and quantitative
      assessment (n = 7) indicated that the extent of the low SI area before
      reperfusion was approximately the same as that of the necrotic region shown by
      TTC staining, while the high SI area seen after reperfusion was obviously larger
      than both the necrotic region and the low SI area on pre-reperfusion images. The
      correlation coefficient between low SI area and necrotic area was 0.98, and
      between high SI area and necrotic area was 0.80. These results suggest that Gd
      DTPA-enhanced MRI may be useful for quantification of infarct size in occlusive
      myocardial infarction but it may overestimate in reperfused one.

PMID- 8293740
TI  - MRI alterations as an early finding in Creutzfeld-Jakob disease.
AB  - Two cases of Creutzfeldt-Jakob Disease (CJD) are reported. In both cases,
      pathologically confirmed, magnetic resonance imaging (MRI) showed bilateral
      altered signal areas in the basal ganglia, early in the course of the disease.
      The CT scan, although performed later than MRI, confirmed these findings. Only in
      one patient did electroencephalography (EEG) show typical triphasic sharp-waves,
      but this support to clinical diagnosis was obtained 1 month after the appearance
      of MRI alterations.

PMID- 8293741
TI  - A retrospective study of large ovarian masses in paediatric practice.
AB  - A retrospective review of 15 patients presenting over a 15-year period with large
      ovarian tumours is reported in whom the presenting complaint was gross abdominal
      swelling. Histological confirmation of all the tumours was obtained. There were
      three serous cystadenomas, two mucinous cystadenomas, one Brenner tumour, three
      benign juvenile granulosa cell tumours--two not menstruating, three benign
      teratomas--one not menstruating, one malignant teratoma--not yet menstruating,
      one malignant embryonic carcinoma and one hydatid disease. All the patients are
      currently well. The radiological findings are described and some of the marked
      differences in the radiological appearances of adult and paediatric ovarian
      masses are illustrated.

PMID- 8293742
TI  - CT manifestations of peritoneal leiomyosarcomatosis.
AB  - CT findings of six patients with pathologically proved malignant peritoneal
      disease secondary to leiomyosarcomas were reviewed. Peritoneal implants, hepatic
      metastases and ascites were found in five, five and two, of the six patients,
      respectively. Neither lymphadenopathies, diffuse peritoneal mesenteric
      involvement, nor intralesional calcification were observed. Although infrequent,
      peritoneal leiomyosarcomatosis should be included in the differential CT
      diagnosis of carcinomatosis.

PMID- 8293743
TI  - Pulmonary infarction: sonographic appearance with pathologic correlation.
AB  - OBJECTIVE: Peripheral pulmonary lesions are detectable by ultrasound, the aim of
      this study was to compare sonograms of pulmonary infarctions with their
      pathological reports. SUBJECTIVE: A total of 26 lung infarcts in 15 non-fixed
      autopsy lungs of patients showing necroscopically pulmonary embolism were
      examined sonographically in a water-bath no later than 5 h after autopsy with a 5
      or 7.5-MHz sector scanner. Five of these patients were suspected of pulmonary
      embolism and underwent sonographic examinations shortly before their death.
      RESULTS: Ultrasound showed mainly wedge-shaped (n = 18), hypoechoic areas. Their
      location, form and size corresponded exactly with pathological findings. Fresh
      infarcts were homogeneous and more hypoechoic. Older infarcts were well
      demarcated and showed a hyperechoic reflex in the center corresponding to the
      bronchiole; this was a sign of segmental involvement. In two cases it was
      possible to differentiate thromboembolically congested afferent blood vessel
      directed to the hilus. Ultrasound images from five living patients were similar
      to the image of the autopsy lung. CONCLUSION: In accordance with clinical studies
      these observations suggest that transthoracic sonography can be an efficient
      technique in the detection of pulmonary infarction, as well in an early
      reperfusionable stage as in distinguished infarct formation.

PMID- 8293744
TI  - Neural network approach for computer-assisted interpretation of ultrasound images
      of the gallbladder.
AB  - Multi-formatted films of 90 ultrasound examinations of the gallbladder (stones 56
      cases, sludge 20 cases, hydrops five cases, normal gallbladder nine cases) have
      been digitalized and stored in a personal computer. Image data of each
      examination was processed to extract a 19-dimensional vector that represents the
      essential diagnostic information of each examination. This vector was evaluated
      by three different classification algorithms: (1) classical nearest neighbor
      principle, (2) classical linear discriminant analysis, (3) multilayered
      backpropagation neural network. The correct classification rate was 64% (58/90)
      for the nearest neighbor principle, 97% (87/90) for the linear discriminant
      analysis, and 99% (89/90) for the backpropagation neural network. We conclude
      that, (1) automated classification of ultrasound images is possible for limited
      diagnostic problems, (2) a neural network approach can be used successfully for
      that goal, and (3) the efficiency of the more flexible neural network approach is
      comparable to large-scale classical methods.

PMID- 8293745
TI  - Radiological findings in cases of gallbladder carcinoma.
AB  - Radiological findings in 80 cases of gallbladder carcinoma are analysed
      retrospectively. Seventy-nine of the patients had been examined by US
      (ultrasonography), 37 by CT (computed tomography), 26 by PTC (percutaneous
      transhepatic cholangiography), 17 by ERCP (endoscopic retrograde cholangio
      pancreaticography), nine by angiography and 27 by US-guided FNB (fine needle
      biopsy). US showed the primary tumour in 68% and CT in 57%. In 67 cases the
      tumour had spread outside the gallbladder area, causing bile duct obstruction in
      41. US showed the bile duct obstruction in 39 of these cases and CT in 20 out of
      22 cases. US showed 73% of the cases that had spread to the liver; the
      sensitivity being 68% for direct invasion and 88% for peripheral liver
      metastases. The corresponding percentages for CT were 68, 67 and 75%,
      respectively. In lymph node enlargement, US showed the nodes in 70% of cases and
      CT in 52%. PTC showed either stenosis or total obstruction in 25 cases and failed
      in one case. ERCP showed a tumour in 76% and failed in 24%. Angiography failed to
      show the primary tumour in two instances out of nine. The results indicate that
      current imaging methods are insufficient for the accurate staging of gallbladder
      carcinoma.

PMID- 8293746
TI  - Percutaneous choledochoscopic biliary tract stone removal: experience in 645
      consecutive patients.
AB  - Our experience in non-operative retrieval of biliary tract stones through PTCS
      (percutaneous transhepatic cholangioscopy, n = 103) and POC (post-operative
      choledochoscopy, n = 542) plus the use of Dormia basket and EHL (electrohydraulic
      lithotripsy) is presented. The results of transhepatic and T-tube routes are
      compared, with emphasis on the technical difficulties encountered. The success
      rates were 96% and 97% in POC and PTCS, respectively. No mortality was related to
      these procedures. Intrahepatic duct angulation and stricture were the factors
      most often responsible for failure. Postoperative choledochoscopic stone removal
      is safe and the method of choice for retained biliary tract calculi, while PTCS
      is highly indicated for those high-risk patients with or without previous biliary
      surgery. POC and PTCS have, therefore, their own indications and differ in their
      clinical applications.

PMID- 8293747
TI  - Ultrasonography is more effective than computed tomography in excluding invasion
      of the carotid wall by cervical lymphadenopathies.
AB  - Twelve patients with head and neck cancer, bulky lymphadenopathies, and clinical
      suspicion of carotid artery infiltration, had preoperative CT and US. The results
      of both techniques were correlated with surgical findings (one case of invasion
      and 11 of non-invasion), to evaluate the role of CT and US in the preoperative
      diagnosis of tumor invasion of the carotid wall. While CT showed a high level of
      failures (11 false positives and one true positive), US (one true positive, one
      false negative, and 10 true negatives) appears to be an easy and helpful method
      for predicting non-invasion of the carotid wall. However, the usefulness of US in
      detecting invasion cannot be evaluated, due to the limited number of positive
      cases.

PMID- 8293748
TI  - Extravasation of salivary secretions and mumps infection of the submandibular
      gland.

PMID- 8293749
TI  - Insufficient hemodialysis access fistulas: 18 months' experience in laser
      supported dilation.
AB  - Patients with end-stage renal failure disease frequently develop venous stenoses
      or occlusions in their hemodialysis access fistulas caused by intimal fibrosis. A
      complete dilation with high pressure balloons up to 20 atm may be unsuccessful in
      those cases. We investigated two new pulsed dye laser devices for the ablation of
      obstructions, which were not adequately treatable with a previous balloon
      angioplasty. From November 1990 to April 1992 a total of 154 percutaneous
      transluminal angioplasties (PTAs) of hemodialysis access fistulas were performed.
      In 23 of them an additive laser angioplasty was necessary. Twenty patients with
      Cimino fistulas presented 28 stenoses and two occlusions, and three Goretex loops
      presented all occlusions. Two pulsed dye laser devices emitting at 504 nm and 595
      nm wavelength were tested. Technical success was achieved in 22/23 cases, but
      clinical success was obtained in 20/23 patients because two early reocclusions
      caused by thrombosis appeared. Five restenoses occurred 2, 3, 10, and in two
      cases 14 months after angioplasty with a mean follow-up period of 13.5 (5-18)
      months. Pulsed dye laser ablation in hemodialysis access fistula lesions due to
      intimal fibrosis is a valuable enrichment of radiological recanalization
      techniques and an alternative to surgery if stand alone balloon PTA fails.

PMID- 8293750
TI  - A double-blind study comparing safety, tolerability and efficacy of iodixanol 320
      mgI/ml and ioxaglate 320 mgI/ml in cerebral arteriography.
AB  - Iodixanol is a new nonionic dimer, isotonic with blood at all concentrations.
      Iodixanol 320 mgI/ml was compared in a double-blind, randomized study to the
      ionic dimer ioxaglate 320 mgI/ml for evaluation of safety and efficacy parameters
      during cerebral arteriography. Eighty adult patients were enrolled and all
      completed the trial. Radiographic efficacy was assessed from the diagnostic
      information and the radiographic density. Safety was evaluated by recording
      discomfort and other adverse events, changes in ECG, heart rate and blood
      pressure, changes in intra-arterial blood pressure and circulation time. No
      difference between the two contrast media were noted radiographically. No
      clinically important changes from baseline or between the two contrast media were
      found in ECG, heart rate, blood pressure or intra-arterial blood pressure.
      Although not statistically significant, a somewhat longer mean circulation time
      was found with iodixanol, probably due to its slightly higher viscosity.
      Injection-associated warmth sensation and pain were more intense with ioxaglate
      than with iodixanol, and pain was statistically more frequent after injection of
      ioxaglate. A high incidence of adverse events other than discomfort is reported
      in this study, mainly related to the selective arteriographic procedure itself.
      The adverse events related to the contrast medium were more frequent with
      ioxaglate (27% of the total number of adverse events) than with iodixanol (10%).
      The new isotonic nonionic dimer iodixanol offers significantly better comfort to
      the patient than does ioxaglate. This is an important feature, especially in
      relatively risky procedures that are unpleasant for the patients, such as
      conventional cerebral angiography.

PMID- 8293751
TI  - Tuberculous Addison's disease. Utility of CT in diagnosis and follow-up.
AB  - The computed tomographic (CT) findings in five patients with tuberculous
      Addison's disease were evaluated. All patients had extra-adrenal tuberculosis.
      Two patients had enlarged adrenal glands with calcifications at the times of
      diagnosis. Follow-up CT from 4 to 30 months showed a progressive decrease in the
      size of adrenal glands from bilateral enlargement to small calcified glands and
      provides a clue to the etiology of Addison's disease and proper therapy.

PMID- 8293752
TI  - Mechanisms and control of repolarization.
AB  - This paper describes and discusses interventions that may lead to prolongation of
      the action potential. Special emphasis is given to regulation by drugs. The
      results of studies focusing on the modulation of inward and outward currents are
      presented in detail. Specific attention is given to Na+, Ca2+, K+ and Cl- channel
      currents and their components.

PMID- 8293753
TI  - Multiple modes of termination of re-entrant excitation around an anatomic barrier
      in the canine atrium during the action of d-sotalol.
AB  - In the chronically-instrumented animal and the isolated blood perfused heart,
      atrial re-entry via a fixed path around an anatomic obstacle has been described
      and is terminated by the class III antiarrhythmic agent d-sotalol. The precise
      mechanism by which d-sotalol terminates this arrhythmia is not known. In the
      present study, right atrial (RA) activation sequences in the isolated, coronary
      artery perfused canine heart (n = 5) during episodes of sustained flutter and
      drug administration were determined. A fixed array of bipolar electrodes was used
      to record endocardial electrograms from 96 sites on the RA simultaneously. Maps
      of all control flutters showed that the rhythm was due to persistent circus
      movement of the impulse around the tricuspid valve ring. d-Sotalol was effective
      in terminating atrial re-entry in this model. In all episodes, block of the
      excitatory impulse in a specific region of the re-entrant circuit accompanied
      these terminations. However, the events preceding the occurrence of block of the
      impulse were not similar. Two different modes of termination are described. The
      class III antiarrhythmic agent d-sotalol can terminate atrial re-entry in several
      ways. In one mode, complete conduction block of the re-entering impulse within
      the fixed path occurs to terminate the rhythm. In the other mode, interruption of
      the original re-entrant circuit occurs when there is failure of a lateral
      boundary. In both modes cycle length (CL) oscillations are observed.

PMID- 8293754
TI  - Class III actions in an experimental model of ventricular tachycardia.
AB  - Simplified models of re-entry may help in our understanding of the
      electrophysiologic effects of class III drugs. In a model of re-entrant
      ventricular tachycardia around a ring of epicardium in Langendorff-perfused
      rabbit hearts, the electrophysiologic effects of class III antiarrhythmic drugs
      were studied and compared to those of class I drugs. Class III drugs were
      effective in terminating fast re-entrant ventricular tachycardias. Prolongation
      of the refractory period without affecting conduction velocity resulted in a
      closure of the excitable gap and collision of the head of the propagating impulse
      against its own tail of refractoriness. In slow ventricular tachycardias, despite
      a similar increase in refractory period, the excitable gap remained large enough
      to allow perpetuation of the tachycardia.

PMID- 8293755
TI  - Early after-depolarizations and torsade de pointes: implications for the control
      of cardiac arrhythmias by prolonging repolarization.
AB  - Common clinical features in drug-induced torsade de pointes include hypokalemia
      and cycle-length prolongation just prior to initiation of the arrhythmia. In
      canine Purkinje fibres, drugs known to be associated with torsade de pointes,
      such as quinidine, sotalol or N-acetylprocainamide, consistently produce early
      after-depolarizations (EADs) and triggered activity at slow drive rates; for
      quinidine, these abnormalities are exaggerated by low extracellular potassium.
      Triggered activity can be abolished in vitro in two ways. First, action-potential
      shortening with abolition of EADs can be accomplished by increasing stimulation
      rates, beta-stimulation and action-potential shortening antiarrhythmics such as
      lidocaine. Second, triggered activity can be suppressed, with less prominent
      effects on EADs, by magnesium, alpha- and/or beta-adrenergic blockade and calcium
      channel blockers. The parallels between these in vitro findings and clinical
      torsade de pointes suggest that EADs and triggered activity play a role in the
      genesis of the clinical arrhythmia. Further research directed at determining the
      mechanisms underlying the cellular abnormalities and their propagation to the
      whole heart should yield information that will increase the safety of
      antiarrhythmic therapy.

PMID- 8293756
TI  - Comparative efficacy of sotalol and class I antiarrhythmic agents in patients
      with ventricular tachycardia or fibrillation: results of the Electrophysiology
      Study Versus Electrocardiographic Monitoring (ESVEM) Trial.
AB  - The ESVEM Trial was a randomized prospective study to compare the predictive
      accuracy of electrophysiologic testing (EPS) to ambulatory electrocardiographic
      monitoring (Holter monitoring--HM) for long-term drug therapy of sustained
      ventricular tachyarrhythmias. 486 patients with documented ventricular
      tachycardia or resuscitated sudden death were randomized to EPS (n = 242) or HM
      (n = 244) and underwent serial drug testing with up to six antiarrhythmics; in
      the EPS limb a drug efficacy prediction was achieved in 108 patients (45%),
      compared to 188 (77%) in the HM limb (P < 0.001). Efficacy predictions were most
      frequent with sotalol therapy. During long-term follow-up of the 296 patients
      discharged on a drug predicted to be effective, there were 151 recurrences of an
      arrhythmic event; there were no differences in actuarial rates of arrhythmia
      recurrence between EPS and HM. With multivariate testing of 14 variables, only
      sotalol therapy and absence of prior antiarrhythmic therapy were associated with
      a significant reduction in risk of arrhythmia recurrence.

PMID- 8293757
TI  - Acute and chronic antiarrhythmic efficacy of d-sotalol in patients with sustained
      ventricular tachyarrhythmias.
AB  - To evaluate the clinical efficacy of d-sotalol, 84 patients with a history of
      sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), who had
      inducible sustained VT/VT at baseline electrophysiologic study (EPS), were
      investigated after intravenous (IV) d-sotalol (1.5-2.5 mg.kg-1). A total of 29
      additional patients received only oral d-sotalol, (400-600 mg.day-1). Acute
      success of antiarrhythmic therapy was defined as suppression of inducible
      sustained VT/VF. The overall success rate of IV d-sotalol was 38% (32/84) after a
      mean of 4.3 drugs failed to suppress inducibility. A 78% success rate (31/40) was
      demonstrated in patients who were also assessed after oral d-sotalol. Torsade de
      pointes type VT was seen in one patient. After 1 year, only 16% of patients with
      a positive EPS had a recurrence compared to 43% of patients with a negative EPS
      (P < 0.05). Estimated survival rates were 95 and 88% after 1 and 2 years of
      follow-up, respectively. Only five of 56 patients discontinued d-sotalol therapy
      because of adverse effects. IV d-sotalol appears to be an effective
      antiarrhythmic agent. Its long-term efficacy is predictable on the basis of
      therapy guided by electrophysiologic testing in patients with refractory
      ventricular tachyarrhythmias. The efficacy of d-sotalol seems comparable to that
      reported for d,l-sotalol.

PMID- 8293758
TI  - Antiarrhythmic drugs and torsade de pointes.
AB  - In the past decade there has been much progress in understanding the clinical
      features and associations of drug-induced long QT syndromes, their inter
      relationships with other long QT syndromes, and electrophysiological mechanisms
      that may be involved in the development of torsade de pointes, the major
      proarrhythmic correlate of prolonged repolarization. The most likely
      electrophysiologic basis for torsade de pointes is the development of after
      depolarizations facilitated by hypokalemia, bradycardia and lengthened QT
      intervals. Torsade de pointes can be produced by all antiarrhythmic agents that
      lengthen repolarization, although the precise incidence varies with different
      agents and is not quantitatively related to the degree of QT prolongation.
      Quinidine, disopyramide and procainamide (with its metabolite N-acetyl
      procainamide) are strongly concordant in the production of torsade de pointes.
      Such concordance suggests that there is an individual predisposition to the
      induction of early after-depolarizations (EAD) with exposure to agents that
      prolong repolarization. However, concordance with agents or other classes, such
      as sotalol, is less certain, and amiodarone appears to be discordant. The
      discordance between potency in prolonging the QT interval and the proclivity to
      induce torsade de pointes may hold the key to separating the salutary therapeutic
      antiarrhythmic effects from adverse proarrhythmic effects of class III agents.
      There is an optimistic perception that the development of new agents that
      potently prolong repolarization will give a modern realization of the old concept
      that prolongation of refractoriness is a uniquely powerful anti-re-entrant,
      antitachyarrhythmic action.

PMID- 8293759
TI  - New class III antiarrhythmic drugs.
AB  - Several new antiarrhythmic compounds with pure class III activity are currently
      under development and seem to possess considerable antiarrhythmic potential. The
      primary electrophysiological action of class III agents is selective prolongation
      of repolarization without conduction slowing. This effect is usually mediated by
      block of one or more potassium currents which results in prolongation of the
      action-potential duration and refractoriness in both atrial and ventricular
      myocardium. The magnitude of increases in effective refractory period decreases
      as the heart rate is increased, i.e. these drugs display 'reverse use
      dependence'. Initial animal and clinical studies have shown that class III agents
      are effective against re-entrant supraventricular and ventricular arrhythmias
      without having any important negative inotropic effect in the compromised
      ventricle. Animal studies have also suggested that these drugs may be useful in
      suppressing postinfarction arrhythmias and preventing arrhythmic sudden death.
      However, concerns have been raised by reports of substantial proarrhythmic
      tendency associated with these drugs, mainly in the form of torsade de pointes.
      Careful clinical evaluation is required to establish the clinical benefits of
      these potentially promising new compounds.

PMID- 8293760
TI  - Coronary endothelium and smooth muscle--basic aspects and clinical consequences.
      Symposium, 26-28 November 1992, Berlin. Proceedings.

PMID- 8293761
TI  - Calcium entry blockade may prevent cyclosporin A-induced hypersensitivity to
      angiotensin II and endothelial dysfunction in the rat aorta.
AB  - Vascular smooth muscle dysfunction after chronic treatment with cyclosporin A was
      in part explained by chronically augmented calcium influx leading to calcium
      overload. The potential protective effect of calcium antagonism with diltiazem as
      regards endothelial and vascular smooth muscle reactivity was investigated during
      chronic treatment with cyclosporin A. Male Wistar rats were orally treated for 6
      weeks with either cyclosporin A (30 mg.kg-1 x day-1 in 1 ml, n = 8), with the
      vehicle alone (n = 10), with diltiazem (60 mg.kg-1 x day-1, n = 10) or with a
      combination of cyclosporin A and diltiazem (30 mg.kg-1 x day-1 and 60 mg.kg-1 x
      day-1, n = 8), respectively. Rings of the isolated thoracic aorta were mounted in
      organ chambers to measure isometric force. Chronic treatment with diltiazem alone
      did not affect the responsiveness to any of the drugs tested, but the
      augmentation of contractions to angiotensin II (10(-9) to 10(-6) M) after
      treatment with cyclosporin, was prevented by co-treatment with diltiazem. Co
      treatment with diltiazem, however, did not affect the response to potassium
      chloride (20-80 mM), endothelin-1 (10(-9) to 10(-7) M) or phenylephrine (10(-9)
      to 10(-6) M). Endothelium-dependent relaxations to calcitonin gene-related
      peptide (CGRP, 10(-10) to 10(-7) M) and acetylcholine (10(-8) to 10(-5) M) were
      reduced in cyclosporin A treated rats. Co-treatment with diltiazem normalized the
      response to CGRP. The response to acetylcholine was not significantly
      affected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293762
TI  - Cyclosporin and oxidized low density lipoproteins synergistically potentiate
      vasoconstriction: influence of the endothelium.
AB  - Cyclosporin (CyA) and oxidatively modified low density lipoproteins (Ox-LDL) are
      known to cause vasoconstriction, observations of possible clinical significance
      because lipid disorders favouring the formation of Ox-LDL are common in patients
      under CyA treatment. We hypothesized that co-incubation of isolated arteries with
      Ox-LDL and CyA might enhance their respective influence on vascular tone. We
      investigated vascular reactivity of isolated intact rabbit renal arteries pre
      incubated with CyA in the presence of native and Ox-LDL. Following pre-incubation
      of the arteries with CyA (10 micrograms.ml-1, 90 min), both unstimulated vascular
      tone as well as norepinephrine-induced vasoconstrictions remained unchanged
      compared to controls preincubated with the CyA-vehicle di-methyl-sulfoxide. Ox
      LDL (100 micrograms.ml-1) in the absence of CyA significantly enhanced
      vasoconstrictions to threshold concentrations of norepinephrine (78 +/- 10
      microns at 30 nM). However, following CyA treatment, the Ox-LDL-induced
      potentiation of contractile responses to norepinephrine was further enhanced (157
      +/- 19 vs 71 +/- 11 microns). Native LDL had no influence on vascular tone.
      Potentiation of norepinephrine-induced vasoconstriction by Ox-LDL took place in
      either endothelium-denuded or endothelium-intact arteries, whereas the further
      enhancement of vascular tone following CyA treatment was seen only in endothelium
      intact segments. Endothelium-dependent dilations to acetylcholine were fully
      preserved following Ox-LDL and CyA treatment. Indomethacin, saralasin, and the
      thromboxane A2 antagonist daltroban had no influence, whereas the Ca2+
      antagonists nitrendipine and verapamil prevented the potentiation of
      vasoconstrictions by CyA and Ox-LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293763
TI  - Biotransformation to nitric oxide of organic nitrates in comparison to other
      nitrovasodilators.
AB  - Nitrovasodilators are prodrugs which, although chemically heterogenous, exert
      their pharmacodynamic action via a common pathway, i.e. the release of nitric
      oxide (NO). The NO, which results from metabolism of nitrovasodilators in
      vascular and non-vascular cells, stimulates the cytosolic enzyme guanylyl cyclase
      leading to an increase in the concentration of intracellular cyclic guanosine
      monophosphate (cGMP). In general, the rate of NO generation from the individual
      compounds correlates well with the extent of cGMP increase and their potency to
      relax vascular tissue. The amounts of NO generated are sufficient to inhibit
      platelet aggregation and to induce disaggregation. Nitrovasodilators thus mimic
      the action of endothelium-derived relaxing factor (EDRF). After more than a
      century of empiric use, the application of nitrovasodilators today may be
      regarded as causal therapy, since these drugs act by substituting an endogenous
      factor, the production or release of which is impaired under pathophysiological
      circumstances associated with endothelial dysfunction. Marked differences exist
      between individual compound classes with regard to bioactivation mechanisms,
      cofactor requirements, and the extent and nature of the concomittant formation of
      metabolites other than NO. This review describes the discovery of the mode of
      action of nitrovasodilators and our current understanding of the pathways
      involved in their bioactivation and biodegradation with special emphasis on the
      enzymatic and non-enzymatic metabolism of organic nitrates. In addition, the in
      vivo metabolism of NO is reviewed briefly.

PMID- 8293764
TI  - Inhaled nitric oxide: its effects on pulmonary circulation and airway smooth
      muscle cells.
AB  - Nitric oxide (NO), an endothelium-derived relaxing factor synthesized from L
      arginine by the enzyme NO synthase, has been identified as an important, short
      acting, endogenous vasodilator. In patients with pulmonary hypertension, inhaling
      a low dose of NO as a gaseous vasodilator has been shown to induce selective
      vasodilation in ventilated lung areas. It achieves this without the disadvantages
      attributed to systemically infused vasodilators e.g. systemic vasodilation and an
      increase in pulmonary right-to-left shunt with a consecutive fall in PaO2. Thus,
      inhaled NO reduces pulmonary hypertension in the severe adult respiratory
      distress syndrome and in persistent pulmonary hypertension of the newborn, and
      improves arterial oxygenation by redistributing pulmonary blood flow away from
      the shunt and towards areas with almost normal ventilation/perfusion ratios. The
      bronchodilatory effect of NO may be an alternative therapy for treating asthma
      and bronchospasm.

PMID- 8293765
TI  - Modulation of vascular cyclic nucleotide phosphodiesterases by cyclic GMP: role
      in vasodilatation.
AB  - Vascular smooth muscle contraction is modulated by an increase in cyclic
      guanosine monophosphate (cyclic GMP) subsequent to nitric oxide production by
      endothelial cells. The participation in this vasodilatation of specific cyclic
      adenosine monophosphate (cyclic AMP) phosphodiesterase (PDE) forms differentially
      sensitive to cyclic GMP is unclear. Chromatographic separation and
      pharmacological characterization show that the specific cyclic AMP PDE of
      endothelial cells is of the PDE IV subtype, known to be insensitive to cyclic
      GMP, whereas cyclic AMP PDEs of vascular smooth muscle are both cyclic GMP
      sensitive and -insensitive (subtypes PDE III and PDE IV, respectively). The role
      of these PDE forms in the modulation of vascular contraction was investigated in
      rat aorta with and without endothelium by using specific inhibitors of PDE III
      and PDE IV as relaxing agents. PDE III inhibitors (milrinone, CI 930, SK&F 94120
      and LY 195115) similarly relax rat aorta with and without endothelium and their
      potencies are not modified by NG-monomethyl-L-arginine (L-NMMA, 300 microM) or L
      arginine (1 mM). However, PDE IV inhibitors (rolipram and denbufylline) only
      induce relaxation of aorta with endothelium, this relaxation being reversed by
      addition of L-NMMA and restored by addition of L-arginine. Relaxation studies
      performed with PDE IV inhibitors in the presence of low concentration of agents
      that increase cyclic AMP or cyclic GMP, clearly show that PDE IV inhibitor
      potencies are markedly increased by cyclic GMP elevating agents, by PDE III
      inhibitors and by the presence of functional endothelium.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8293766
TI  - Control of vascular tone by renin and angiotensin in cardiovascular disease.
AB  - The tools which have led to a better understanding of the role of the renin
      angiotensin system in determining the tone of peripheral arteries in
      cardiovascular disease consist of highly specific and sensitive methods to
      measure the different components of the renin-angiotensin system and in specific
      probes used to inhibit the renin-angiotensin system at several points of the
      enzymatic cascade. The therapeutic efficacy of these more and more specific
      probes undoubtedly provides strong circumstantial evidence that angiotensin II
      plays an important role in determining peripheral vascular tone. While this has
      considerably increased our understanding of the regulatory mechanism involved in
      blood pressure maintenance in normotensive subjects and hypertensive patients,
      the role of the renin-angiotensin system as an aetiological factor in the
      development of essential hypertension still remains unclear.

PMID- 8293767
TI  - Local regulation of vascular tone by bradykinin and angiotensin converting enzyme
      inhibitors.
AB  - Part of the vasodilator response to angiotensin converting enzyme (ACE)
      inhibitors depends on stimulation of bradykinin receptors, but in most studies
      the anticipated increase in plasma kinin concentration during ACE inhibition was
      not detected. We investigated the role of local ACE inhibition on endothelial
      control of vascular tone. Rings of bovine coronary, renal and tail arteries, as
      well as human coronary arteries, were mounted in organ chambers so that the
      isometric force could be recorded. The ACE inhibitors, captopril, fosinoprilat,
      enalaprilat, lisinopril, and ramiprilat alone had no affect on the vascular tone
      of bovine coronary arteries with endothelium. However, these ACE inhibitors did
      potentiate relaxations to bradykinin and the slowly degradable bradykinin
      derivative [Hyp3-Tyr(Me)8]-bradykinin (3 x 10(-11) M). A similar response was
      observed in human coronary arteries. The response was not observed in rings of
      any vessel without endothelium, or after incubation with nitro-L-arginine (10(-4)
      M), or the bradykinin2-receptor antagonists Hoe 140 (10(-8) M). The sensitivity
      to bradykinin was higher and the potentiating effect of ACE inhibition larger in
      the bovine coronary artery than in the renal and tail artery. Thus, ACE
      inhibition causes selective coronary vasodilation by potentiating the bradykinin
      induced release of nitric oxide from the endothelium. The related mechanism
      underlying these effects must occur at the surface or within the arterial wall
      and seems to be independent of the degradation of the kinins.

PMID- 8293768
TI  - Angiotensin-converting enzyme inhibitors unmask endogenous kinin production by
      bovine coronary artery endothelium.
AB  - The angiotensin converting enzyme (ACE) inhibitors, moexiprilat and ramiprilat,
      relaxed preconstricted endothelium-intact bovine coronary artery rings and
      enhanced the relaxant response to bradykinin. The relaxation was observed in the
      presence of a cyclooxygenase inhibitor and without previous exposure to
      bradykinin. ACE inhibitor-dependent relaxation was attenuated by the selective B2
      kinin receptor antagonist, Hoe 140, and completely abolished by removal of the
      endothelium. Bradykinin or moexiprilat also significantly increased the cyclic
      guanosine monophosphate (cGMP) content of these coronary segments, an effect
      which was abolished by the nitric oxide (NO) synthase inhibitor, NG-nitro-L
      arginine (NNA), or by removal of the endothelium. NNA also diminished the
      relaxant response to moexiprilat, but only partially inhibited that to
      bradykinin, suggesting that the ACE inhibitor-induced relaxation was
      predominantly mediated by endothelial NO release, whereas bradykinin acted in
      part by another endothelium-dependent mechanism. These findings indicate that ACE
      inhibitors can elicit endothelium-dependent relaxations presumably by
      facilitating the accumulation of endothelium-derived kinins in or at the vessel
      wall. This local mechanism may significantly contribute to the antihypertensive
      action of these compounds in vivo.

PMID- 8293769
TI  - Coronary vasodilation to acetylcholine, adenosine and bradykinin in dogs: effects
      of inhibition of NO-synthesis and captopril.
AB  - We investigated the effects of inhibition of both nitric oxide (NO) synthesis and
      angiotensin converting enzyme (ACE) on agonist-induced relaxations in the
      coronary system. Chronically instrumented conscious dogs (n = 4) were prepared
      for the measurement of coronary blood flow (CBF), coronary diameter of the left
      circumflex artery (LCX), mean arterial blood pressure (MAP) and heart rate (HR).
      Intracoronary infusions of acetylcholine, adenosine and bradykinin were performed
      after intracoronary pretreatment of either vehicle, L-NAME (6 mg.kg-1), captopril
      (1 mg.kg-1) or both L-NAME+captopril. Acetylcholine bradykinin and adenosine
      caused dose-dependent increases in CBF and LCX. HR increased concomitantly.
      Captopril potentiated the vasodilating effects of bradykinin and acetylcholine on
      LCX and CBF significantly (P < or = 0.05) and those of adenosine slightly. L-NAME
      caused vasoconstriction, hypertension and bradycardia. The effects of
      acetylcholine on CBF were abolished during L-NAME treatment while bradykinin and
      adenosine responses were markedly reduced. When captopril and L-NAME were given
      simultaneously, the vasodilator responses to bradykinin but not to acetylcholine
      or adenosine were partially restored (P < or = 0.05). We conclude that in vivo,
      (a) adenosine possibly elicits endothelium-dependent dilation; (b) adenosine and
      bradykinin act in part independently of the L-arginine/NO pathway; (c)
      vasodilation to acetylcholine is potentiated by acute ACE inhibition via NO
      dependent mechanisms.

PMID- 8293770
TI  - Modulation of sympathetic control by ACE inhibitors.
AB  - ACE inhibitors may influence the actual concentrations of the peptides
      angiotensin I, angiotensin II and bradykinin. Since all three peptides are able
      to modulate catecholamine release, a change in noradrenaline and adrenaline
      release should be expected when angiotensin I converting enzyme (kininase II) is
      inhibited. Furthermore, converting enzyme inhibitors may also act indirectly on
      sympathetic membranes affecting, for instance, the reuptake mechanism of
      noradrenaline. It was shown that chronic ACE inhibition did not change
      biosynthesis, storage or release of catecholamines. However, the reuptake of
      noradrenaline was slightly but significantly diminished by ramipril. Whereas Ang
      I exerted no facilitating action on noradrenaline, bradykinin stimulated
      noradrenaline release dose-dependently, almost during converting enzyme
      inhibition. It is concluded that bradykinin may compensate for the lack of effect
      of converting enzyme inhibitors on catecholamine release.

PMID- 8293771
TI  - Regulation of beta-adrenergic receptors on endothelial cells in culture.
AB  - This study aimed to determine the density of vascular beta-adrenergic receptors
      in cultured endothelial cells and to study the regulation of endothelial
      receptors after exposure to catecholamines and the ACE inhibitors, lisinopril and
      ramiprilat. Membranes from bovine aortic endothelial cells (BAEC) and bovine
      pulmonary artery endothelial cells (BPAEC) showed saturable binding of the
      radioligand [125I]iodocyanopindolol (ICYP). The beta-receptor density and binding
      affinity were comparable in both types of endothelial cells. Isoproterenol
      induced significant down-regulation of beta-receptors (-50%; P < 0.01).
      Incubation (24h) with the ACE inhibitors lisinopril 10(-5) M (+28.8%; P < 0.05)
      and ramiprilat 10(-5) M (+33.7%, P < 0.09) augmented the beta-receptor density in
      BAEC, but lower ACE inhibitor doses had no affect. Incubation with lisinopril 10(
      5) M for 24 h resulted in significantly lower cAMP baseline levels, but did not
      affect cAMP concentrations after stimulation with isoproterenol. These results
      indicate that down-regulation of endothelial beta-receptors occurs during
      prolonged exposure to beta-stimulation, and that high concentrations of ACE
      inhibitors may affect the density of endothelial beta-receptors.

PMID- 8293772
TI  - Cardiac angiotensin II formation: the angiotensin-I converting enzyme and human
      chymase.
AB  - Angiotensin-I converting enzyme (ACE) inhibitors have provided a remarkable
      improvement in the treatment of patients with primary hypertension and congestive
      heart failure. The cardiac renin-angiotensin system is one of the major targets
      of ACE inhibitor therapy since recent studies show that the human heart contains
      high affinity angiotensin II (Ang II) receptors and ACE activity. However, it is
      not clear why ACE inhibitors are more effective than other vasodilators in the
      treatment of patients with congestive heart failure. This gap in knowledge led us
      to study the biochemical mechanism of Ang II formation in the human heart. Such
      studies have only recently been addressed. So far, two Ang II-forming enzymes
      (ACE and human chymase) have been identified. Unlike in the rat heart, the minor
      (10%) component of Ang II-forming activity in the left ventricle is due to ACE,
      whereas the major (80%) component is due to human chymase. This novel cardiac
      serine proteinase has been purified from the human left ventricle and
      characterized, and recently, the cDNA and the gene for this enzyme have been
      cloned. Biochemical characterization revealed that human chymase is the most
      efficient and specific Ang II-forming enzyme described thus far, but the cellular
      and regional distribution of two Ang II-forming enzymes seem to be quite
      different. ACE is localized mainly in endothelial cells and its expression level
      is higher in atria than ventricles whereas chymase is localized in the
      interstitial region of the myocardium and its expression is higher in ventricles
      than atria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293773
TI  - Endothelial control of cell migration and proliferation.
AB  - The vascular endothelium was found to be involved in numerous physiological and
      pathophysiological processes and to act as a gating element in between cellular
      components of the blood and the adjacent tissue. In this respect, endothelial
      cells are especially important for the control of the extravasation of immune
      competent cells and tumour cells and in tissue remodelling. These processes are
      guided by a network of intercellular recognition and transduction mechanisms in
      order to guarantee controlled, selective, target-directed action by extravasating
      cells and for complete functional remodelling of the adjacent tissue.
      Prostacyclin seems to play an important part in this endothelium-dependent
      intercellular crosstalk by modulating cell activation without altering the basal
      cellular mechanisms, as can be shown using stable prostacyclin mimetics, both in
      animal models and in cell culture.

PMID- 8293774
TI  - The paradigm of restenosis following percutaneous transluminal coronary
      angioplasty.
AB  - Restenosis after successful percutaneous transluminal coronary angioplasty
      remains a major clinical problem limiting the long-term efficacy of this
      treatment for coronary artery disease. All clinical attempts to reduce the
      incidence of restenosis have failed. Recent advances in the understanding of the
      cellular biology of restenosis indicate that intimal hyperplasia is the
      predominant cause for restenosis. The neo-intimal proliferative response to
      injury is due to an interaction of platelet-fibrin thrombus and smooth muscle
      cells, release of mitogens, followed by a secretion of extracellular matrix.
      Based on these concepts concerning the biology of restenosis, several proposals
      have been made as regards research into potential forms of therapy. Low molecular
      weight heparin (LMWH) has documented antiproliferative effects on smooth muscle
      cells in cell cultures. Animal studies with LMWH in rabbits have demonstrated
      considerable inhibition of smooth muscle cell proliferation during the first 7
      days after balloon angioplasty, resulting in only a moderate increase of intimal
      wall thickness after 28 days. In a first pilot study, application of LMWH was
      adjusted according to the dosage that resulted in a significant reduction of
      smooth muscle cell proliferation in the experimental setting. A specific delivery
      protocol was used, according to the previous documented time course of smooth
      muscle cell proliferation after vascular injury. The results of this safety trial
      indicate a promising therapeutic option for prevention of restenosis following
      coronary angioplasty.

PMID- 8293775
TI  - Basic cellular mechanisms of coronary bypass graft disease.
AB  - The internal mammary artery (IMA) grafts have a higher patency than the saphenous
      vein (SV) grafts. The biological properties of the arterial and venous grafts
      (i.e. endothelial and smooth muscle cell function) are crucial determinants of
      graft function. The endothelial cells in arterial grafts release larger amounts
      of endothelium-derived nitric oxide formed from the precursor amino acid L
      arginine in response to several vasoactive hormones than do venous grafts. In
      IMA, platelet-derived adenosine nucleotides activate the endothelium to release
      nitric oxide, thereby causing vascular relaxation, while in the saphenous vein
      this important protective mechanism is absent. Therefore, platelet-derived
      thromboxane A2 and serotonin evoke marked vasoconstriction in the saphenous vein
      in spite of an intact endothelium. Smooth muscle cell growth plays a significant
      part in intimal thickening and vascular occlusion of bypass grafts, in
      particular, SV grafts. Mechanical forces such as pulsatile stretch and platelet
      derived growth factor are potent mitogens for SV but not IMA smooth muscle
      proliferation. Hence, the different endothelial and smooth muscle cell function
      of IMA and SV may contribute considerably to the different graft functions in
      patients with coronary artery disease.

PMID- 8293776
TI  - Dyslipoproteinaemia, signal transduction, and angiogenesis.
AB  - Hyperlipidaemic states are associated with endothelial cell dysfunction which may
      in part be related to the accumulation of toxic lipoprotein degradation products
      in artery walls. One effect of oxidized LDL and its products is to impair
      transmembrane signalling, a process that might alter responsiveness of
      endothelial cells to mitogens. Endothelial cell replication plays a pivotal role
      in the growth of pre-existing arterial channels and in the formation of new
      microvessels (angiogenesis). Experiments in intact rabbits indicate that
      endothelial replication associated with vascular growth is markedly impaired in
      the presence of hypercholesterolaemia, a defect that could play an important role
      in the pathophysiology of occlusive atherosclerotic disease.

PMID- 8293777
TI  - Signal transduction in endothelium-dependent vasodilatation.
AB  - Modulation of vascular tone is one important function of the endothelium. This
      can occur via two principal mechanisms: by modulating the local concentration of
      circulating vasoactive substances (e.g. adenine nucleotides, angiotensin II,
      biogenic amines, bradykinin), and by synthesizing and releasing vasoactive
      autacoids. The most important endothelium-derived vasodilator autacoids are
      nitric oxide (NO) and prostacyclin (PGI2). By counteracting neuro- and myogenic
      vasoconstriction, the continuous release of these autacoids from the vascular
      endothelium represents a sensitive and highly effective local system for
      maintaining an adequate blood flow to the organs. Impaired production of NO (and
      PGI2), either as a result of endothelial injury or dysfunction, has been
      implicated in the pathology of a variety of cardiovascular diseases, such as
      hypertension, hypercholesterolaemia, atherosclerosis and diabetes. Therefore, the
      prevention and/or reversal of the functional and morphological changes of the
      endothelium associated with these diseases is an important therapeutic goal. This
      brief overview covers current knowledge concerning the intracellular pathways
      that link endothelial activation by receptor-dependent and -independent stimuli
      to the formation of NO and PGI2.

PMID- 8293778
TI  - Endothelial control of vascular smooth muscle proliferation in an organ culture
      of human saphenous vein.
AB  - We have investigated the positive and negative regulation of vascular smooth
      muscle cell (VSMC) proliferation by proposed endothelium-derived mediators using
      organ cultures of freshly isolated and surgically prepared human saphenous vein.
      We observed that: (1) whereas platelet-derived growth factor (PDGF) and basic
      fibroblast growth factor (bFGF) are known to stimulate proliferation, agents that
      minic the action of prostacyclin and nitric oxide (NO), inhibit proliferation;
      (2) the production of PDGF, bFGF, prostacyclin and NO are endothelium-dependent
      in veins before culture--PDGF production is induced in VSMC during intima
      formation; (3) removal of endothelium has a net inhibitory effect on intimal VSMC
      proliferation; (4) antibodies to bFGF reduced intimal VSMC proliferation in
      surgically prepared veins. Hence, in this preparation, PDGF, bFGF, prostacyclin
      and NO are all possible endothelium-dependent regulators of VSMC proliferation.
      Use of selective inhibitors (as exemplified here by antibodies to bFGF) and
      reconstitution of endothelium in the organ culture model promise to be valuable
      to test the roles of these mediators further.

PMID- 8293779
TI  - Adenosine metabolism in the guinea pig heart: the role of cytosolic S-adenosyl-L
      homocysteine hydrolase, 5'-nucleotidase and adenosine kinase.
AB  - This study was conducted to elucidate the role of S-adenosyl-L-homocysteine (SAH)
      hydrolase, 5'-nucleotidase and adenosine kinase in the production and removal of
      adenosine in the isolated guinea pig heart during normoxic (95% O2) and hypoxic
      (30% O2) perfusion. Using an adenosine kinase inhibitor (5'-amino-5'-deoxy
      adenosine; 50 microM) and an adenosine deaminase inhibitor (EHNA; 5 microM) the
      total steady-state production rate of adenosine in the heart was estimated to be
      greater than 1.2 nmol.min-1 per g wet wt., during normoxia. Most (95%) of the SAH
      derived adenosine is salvaged by adenosine kinase action. The rate of adenosine
      phosphorylation increased 3-fold when isolated hearts were perfused with hypoxic
      medium, suggesting that adenosine kinase is not substrate-saturated under
      normoxic conditions. The steady-state production of adenosine was also estimated
      during hypoxia (5.9 nmol-min-1 per g wet wt.) and compared with previously
      determined transmethylation rate during hypoxia (1.12 nmol.min-1 x g wet wt.). In
      an attempt to assess the in-vivo activity of cytosolic 5'-nucleotidase, the 5'
      AMP pool was labelled by perfusing the isolated hearts with tricyclic nucleoside
      (TCN) which became phosphorylated (TCN-P). The release rate of both adenosine and
      TCN in the post-labelling phase was increased by hypoxic perfusion, suggesting
      that the increased rate of 5'-AMP hydrolysis may be due to increased availability
      of substrate, as well as activation of 5'-nucleotidase. Our findings suggest that
      during normoxic perfusion a significant amount of adenosine is derived from an
      apparently oxygen-independent mechanism (cellular transmethylation) whereas
      during hypoxic perfusion hydrolysis of adenine nucleotides to adenosine prevails.

PMID- 8293780
TI  - Characterization of endothelin synthetic pathways and receptor subtypes:
      physiological and pathophysiological implications.
AB  - The endothelins are a family of three widely expressed 21 amino acid peptides.
      Apart from the ability to constrict vascular smooth muscle, they have numerous
      other potent effects, from enhancing mitogenesis to influencing nervous function.
      The pathway of their production involves the initial synthesis of a predominantly
      inactive 38 to 41 amino acid precursor, big endothelin, which is cleaved to the
      active form by an as yet unidentified, but widely distributed, endothelin
      converting enzyme. This enzyme has been partially characterized and appears to be
      a metalloprotease, active at neutral pH, which is inhibited by phosphoramidon.
      However, other enzymes, including those contained in inflammatory cells, can also
      convert big endothelin to its active form. Research in the past 2 to 3 years has
      revealed at least two endothelin receptors. These are widely distributed
      throughout the body and are present, for instance, on vascular and non-vascular
      smooth muscle, nervous tissue, and endothelial and epithelial cells. There is
      also a fairly large degree of heterogeneity between species in the distribution
      of these endothelin receptors. The endothelins have been widely implicated in a
      number of disease states and the recent development of selective and non
      selective antagonists of these receptors, such as BQ-123, PD 142893, and Ro 46
      2005 is finally making available the tools required to elucidate their true
      roles.

PMID- 8293781
TI  - Modulation of chaotic pressure oscillations in isolated resistance arteries by
      EDRF.
AB  - By using non-linear techniques to analyse irregular histamine-induced pressure
      oscillations in an isolated rabbit ear resistance artery, we have shown that the
      pressure oscillations are generated by deterministic rather than stochastic
      mechanisms. The average fractal dimension of the oscillations was between 2 and
      3, thus implying that three (or more) independent control variables were
      necessary to account for the complexity of the dynamics. EDRF suppressed the
      pressure oscillations, but their fractal dimension was not altered by graded
      stimulation of EDRF activity by acetylcholine, or by inhibition of EDRF activity
      with NG-nitro-L-arginine methyl ester (L-NAME) or haemoglobin. This implies that
      EDRF is not one of the primary control variables involved in the genesis of their
      dynamics. The oscillations exhibited distinct 'fast' and 'slow' components, with
      periods of 5-20 s and 1-5 min respectively. The fast subsystem involved ion
      movements at the cell membrane level, and was inhibited by low [Ca2+]o, by
      verapamil (which inhibits voltage-dependent Ca2+ influx) and by
      tetraethylammonium (TEA) and apamin (which block Ca(2+)-activated outward K+
      channels). In contrast, the slow subsystem was selectively inhibited by
      ryanodine, and therefore involved intracellular Ca(2+)-induced Ca2+ release. Each
      of these interventions decreased the fractal dimension to < 2 and thus removed
      one degree of freedom from the dynamics. We conclude that the interaction of a
      fast membrane oscillator and a slow intracellular oscillator generates chaotic
      pressure oscillations which are modulated by EDRF.

PMID- 8293782
TI  - Molecular mechanisms of leucocyte rolling and adhesion to microvascular
      endothelium.
AB  - Leucocyte accumulation and activation can lead to tissue injury subsequent to
      ischaemic insults and reperfusion. Post ischaemic leucocyte recruitment requires
      the coordinated function of at least four sets of adhesion receptors. Leucocyte
      rolling in microvessels is mediated by the selectin family of adhesion molecules
      and their carbohydrate ligands, while firm adhesion and transendothelial
      migration requires binding of integrin molecules on leucocytes to molecules of
      the immunoglobulin superfamily expressed on endothelial cells. Adhesion processes
      are exquisitely regulated at the transcriptional level, but also by
      conformational changes of proteins and enzymatic modifications of carbohydrate
      ligands. This article reviews the current knowledge on the function and
      regulation of adhesion molecules pertinent to leucocyte recruitment.

PMID- 8293783
TI  - Cultivation and characterization of micro- and macrovascular endothelial cells
      from the human heart.
AB  - In order to investigate processes, such as atherosclerosis and inflammation in
      vitro, it is necessary to obtain viable and pure endothelial cell cultures from
      human hearts. To this end, endothelial cells were isolated and cultured from the
      micro- and macrovasculature of human hearts obtained during heart
      transplantation. Isolation of capillaries after enzymatic digestion of heart
      muscle provided a source of microvascular endothelial cells. Contaminating non
      endothelial cells were removed by a new technique: paramagnetic beads linked to
      the lectin ulex europaeus I (UEA-I) were used to select endothelial cells. The
      resulting cultures contained less than 2% of non-endothelial cells, as judged
      from immunological staining and fluorescence-activated cell sorting. Both types
      of endothelial cell displayed typical endothelial properties. They were all
      positive for factor VIII-related antigen and expressed the endothelial-specific
      adhesion molecules, CD31 and E-selectin (ELAM-1), after stimulation with
      cytokines. In addition, they could be labelled with Dil-Ac-LDL, contained
      angiotensin converting enzyme activity and secreted tissue plasminogen activator,
      thus demonstrating that typical endothelial functions were preserved in culture.

PMID- 8293784
TI  - Activation of neutrophils in the microvasculature of the ischaemic and reperfused
      myocardium.
AB  - In 11 rats, the microcirculation of the repeatedly ischaemic (stunned) left
      ventricular myocardium was studied using in vivo fluorescence microscopy.
      Stunning was provoked by six subsequent 10 min ligations of the left anterior
      descending coronary artery, each of them followed by a 20 min reperfusion period.
      In the stunned myocardium showing hypokinetic wall motion, myocardial blood flow
      dropped by 55%; in this region, leukocytes often appeared in slow-flow
      capillaries plugging capillary branches. Closely linking to leukocyte adherence,
      a rise of microvascular permeability was documented by extravascular clouds of
      fluorescent dextran. After nifedipine treatment, in ischaemic regions marked
      dilatation of larger A1 and A2 arterioles was noted, in addition to the ischaemia
      induced dilatation of smaller A3 and A4 arterioles. Furthermore nifedipine and
      nisoldipine reduced the number of adherent leukocytes in post-capillary venules
      and capillaries of the repeatedly ischaemic myocardium. In 12 patients with
      coronary one-vessel disease and without previous transmural myocardial
      infarction, elective coronary angioplasty (PTCA) was performed (balloon inflation
      for 2 min). After elective PTCA of the LAD, a significant rise in the proportion
      of activated neutrophils was noted. After elective 2 min PTCA of the LAD,
      coronary sinus blood samples showed a marked rise of FMLC stimulated superoxide
      anion production, whereas passive deformability decreased considerably.
      Furthermore, an increase in chemotactic activity in coronary sinus blood samples
      was observed.

PMID- 8293785
TI  - Vasoconstriction in response to activated leukocytes: implications for vasospasm.
AB  - Three sets of experiments are presented demonstrating that activated leukocytes
      produce significant vasoconstriction. (1) Responses to human mononuclear
      leukocytes were studied in intact femoral arteries in vitro. Vasoconstriction of
      about 35-40% of the maximal effect obtained with KCl was found with mononuclear
      cells activated by thrombin or complement component C5a, but not with unactivated
      mononuclear cells. This vasoconstriction was endothelium-independent, and could
      not be inhibited by radical scavengers or by pre-treatment of the cells with
      inhibitors of the cyclooxygenase or lipoxygenase pathway. Additional experiments
      suggest that this contractile effect is partially mediated by the release of a
      stable factor. (2) Vascular responses to intra-arterial complement C5a (10 and
      100 micrograms) were studied in the blood-perfused hind limb of normal and
      atherosclerotic monkeys in vivo. C5a injection produced pronounced constriction
      of the hind limb large arteries in atherosclerotic, but not in normal animals.
      Perfusion of the hind limb with a cell-free blood substitute almost abolished C5a
      induced vasoconstriction. These findings suggest that C5a induces
      vasoconstriction by activation of blood cells, probably leukocytes. (3) Vascular
      responses to the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine
      (fMLP), were studied in the human coronary circulation. Intracoronary fMLP (1 x
      10(-8) moles) produced a transient increase in blood flow velocity and a
      significant decrease of the diameter of the epicardial arteries. This effect was
      accompanied by a decrease in leukocyte count in the coronary sinus blood. These
      studies suggest that activated leukocytes produce vasoconstriction by the release
      of vasoactive factor(s), and thus may contribute to the pathogenesis of
      cardiovascular complications in patients with atherosclerosis.

PMID- 8293786
TI  - Endothelium-derived nitric oxide in the control of tissue perfusion and oxygen
      supply: physiological and pathophysiological implications.
AB  - Since the development of specific NO-synthase inhibitors it has become possible
      to study the role of NO in the control of local blood flow and tissue
      oxygenation. Inhibition of NO-synthase induces hypertension and abnormal
      vasoconstriction, as well as tissue hypoxia and impaired adaptation of blood flow
      to increased tissue oxygen demands. These functional alterations are similar to
      those observed in a number of cardiovascular diseases. The present evidence that
      impaired endothelial function is a pathogenetic factor in the development of
      cardiovascular diseases is briefly reviewed.

PMID- 8293787
TI  - Endothelial dysfunction in human atherosclerotic coronary arteries.
AB  - Human coronary arteries were taken from heart transplant patients.
      Arteriosclerotic arteries were more depolarized and constricted over the whole
      PO2 range between 535 and 0 mmHg. During oxygen deficiency, control preparations
      showed a maximal hyperpolarization of delta V = 10.9 mV and a maximal relaxation
      of delta T = 0.466 g. Arteriosclerotic arteries, however, became hyperpolarized
      by merely delta V = 7.1 mV and relaxed by delta T = 0.258 g. In normal coronary
      arteries, indomethacin reduced the hypoxic hyperpolarization and dilatation at 30
      mmHg PO2 by about 51%. The reduction was 27% in arteriosclerotic vessels. The
      complete removal of the endothelium caused a 49% (73% in arteriosclerotic
      coronaries) restriction of dilatory vascular reactivity. The relationship was
      quite similar for a carbogen Krebs solution. The hyperpolarizing and dilatory
      contribution of prostacyclin was 32% in normal and 12% in arteriosclerotic
      coronary arteries. The remainder could be attributed to the basal release of
      endothelium-derived hyperpolarizing factor (EDHF). Thus, it may be concluded that
      in arteriosclerotic blood vessels, prostacyclin (PGI2) synthesis and release are
      predominantly diminished. Finally, we found that the ratio PGI2/EDHF in the
      voltage and tension changes strongly shifted to the PGI2 side with a declining
      oxygen concentration. This is true for normal and arteriosclerotic vessels. In
      addition, a disturbed transmembrane cation distribution in the arteriosclerotic
      coronary vessels may be an additional explanation for the depolarized membrane
      potential and increased muscle tone. [Na+]i of normal arteries amounted to 16.6,
      of arteriosclerotic arteries to 60.9 mmol.l-1; [K+]i values were 134.6 in normal
      and 95.0 mmol.l-1 in arteriosclerotic coronaries, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8293788
TI  - Ethanol-induced contraction of cerebral arteries in diverse mammals and its
      mechanism of action.
AB  - Acute ethanol exposure (8-570 mM) induced potent contractile responses of rings
      in both basilar and middle cerebral arteries, from dogs, sheep, piglets and
      baboons, in a dose-dependent manner. The contractions were reproducible and not
      tachyphylactic. The middle cerebral arteries were found to be more sensitive to
      ethanol than the basilar arteries. No known pharmacological antagonist, tested,
      exerted any effects on ethanol-induced contractions. No differences in
      responsiveness to ethanol in canine cerebral arteries were found between male and
      female animals or between the presence and the absence of endothelial cells.
      Removal of extracellular Ca2+ ([Ca2+]o) partially attenuated ethanol-induced
      contractions, while withdrawal of extracellular Mg2+ ([Mg2+]o) potentiated such
      contractions. In the complete absence of [Ca2+]o, caffeine and ethanol induced
      similar, transient contractions followed by relaxation in K(+)-depolarized
      cerebral vascular tissue. Ethanol-induced contractions were completely abolished
      by pretreatment of tissues with caffeine. Our results suggest that: (a) acute
      ethanol intoxication can induce direct contractions (independent of amine,
      prostanoid or opioid mediation) of diverse mammalian cerebral vascular tissues,
      including those from primates; (b) these contractile responses are heterogeneous
      along the cerebrovascular tree and independent of endothelial cells; (c) in
      addition to a need for [Ca2+]o, an intracellular release of Ca2+ is needed for
      ethanol to induce contractions; and (d) hypomagnesemia or Mg deficiency
      potentiates the contractile effects of ethanol on brain vessels and may be a risk
      factor for ethanol-related, ischemic stroke events.

PMID- 8293789
TI  - Induction of cytochrome P450 1A2 by musk analogues and other inducing agents in
      rat liver.
AB  - We characterized the inducing effects of two musk analogues, musk xylene and musk
      ambrette, on phase I and phase II drug-metabolizing enzymes in rat liver and
      compared their effects with 3-methylcholanthrene, isosafrole and 2(3)
      tertbutylhydroxyanisole (BHA) at 0.1 mmol/kg dose level. Musk xylene and
      isosafrole increased more efficiently the metabolic activation of 2-amino-6
      methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) to mutagen than that of
      benzo(a)pyrene. Musk ambrette increased both the activation of Glu-P-1 and
      benzo(a)pyrene to the same extent. Western blot analyses revealed that musk
      xylene, musk ambrette, isosafrole and BHA induced more strongly cytochrome P450
      1A2 (CYP1A2) in microsomes than CYP1A1. 3-Methylcholanthrene induced CYP1A1 in
      preference to CYP1A2. On the other hand, all drugs except for 3
      methylcholanthrene did not show remarkable increases in phase II enzyme
      activities, such as DT-diaphorase, glutathione S-transferase and UDP
      glucuronyltransferase, at 0.1 mmol/kg dose level. These results show that musk
      xylene, musk ambrette, isosafrole and BHA at the dose level used in this study
      possess the potency to induce CYP1A2 without remarkable induction of CYP1A1 and
      phase II enzyme activities as observed for 3-methylcholanthrene, although they
      have been considered to induce both phase I and phase II drug-metabolizing
      enzymes at higher doses.

PMID- 8293790
TI  - Stable expression of human cytochrome P450 1A1 cDNA in V79 Chinese hamster cells
      and metabolic activation of benzo[a]pyrene.
AB  - A V79 Chinese hamster cell line stably expressing human cytochrome P450 1A1
      (CYP1A1) was obtained by chromosomal integration of the human CYP1A1 cDNA under
      the control of the SV40 early promoter. Chromosomal integration was verified by
      Southern analysis, and effective transcription of the human CYP1A1 cDNA was
      demonstrated by Northern analysis. The CYP1A1 cDNA-encoded protein was
      characterized by Western analysis using anti-rat CYP1A1. Intracellular
      association of CYP1A1 with the endoplasmic reticulum could be visualized by in
      situ immunofluorescence. Crude cell lysates of the V79 derived cell line was able
      to catalyze 7-ethoxyresorufin-O-deethylation (EROD) with an activity of about 50
      pmol min-1 mg-1 total protein, and an aryl hydrocarbon hydroxylase activity (AHH)
      of 25 pmol min-1 mg-1. CYP1A1 dependent cytotoxicity, measured by neutral red
      uptake, and genotoxicity, determined by the frequency of micronucleus formation,
      of benzo[a]pyrene (B[a]P) and trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene
      (B[a]P-7,8-diol) could be demonstrated at substrate concentrations as low as 10
      nM. Thus, this cell line presents a sensitive tool for studying CYP1A1 mediated
      metabolism of polycyclic aromatic hydrocarbons (PAH). B[a]P and the purified (+)-
      and (-)-enantiomers of B[a]P-7,8-diol were compared for their mutagenicity. The (
      )-enantiomer was found to be 3-5-fold more mutagenic than the (+)-enantiomer.

PMID- 8293791
TI  - Protective effect of S12340 on cardiac cells exposed to oxidative stress.
AB  - Oxidative stress induced by reactive oxygen species is one aspect of the
      deleterious mechanisms involved in myocardial post-ischemic reperfusion injury.
      The antioxidant properties of the new molecule S12340 (8-[3-(3,5-diterbutyl-4
      hydroxyphenyl-thio)propyl]-1-oxa-2- oxo-3,8-diazaspiro[4.5]decane) were evaluated
      using three successive in vitro approaches mimicking the cardiac cell damages
      induced by reactive oxygen species released into the reperfused myocardium. (i)
      The effects of S12340 on lipid peroxidation were evaluated using an original cell
      free model of non-enzymatic peroxidation of 1.32 mM arachidonic acid induced by
      reactive oxygen species generated photochemically. S12340 (13.2 microM) inhibited
      by 29% the rate of oxidative fragmentation of monohydroperoxidized arachidonic
      acid into aldehydic products. (ii) S12340 (10 microM) inhibited by 96% and 58%
      the oxidative necrosis of cultured rat cardiomyocytes induced by xanthine oxidase
      (20 mU/ml) and monohydroperoxidized arachidonic acid (30 microM), respectively.
      (iii) Superfusion of guinea-pig papillary muscle with monohydroperoxidized
      arachidonic acid (20 microM) resulted in marked alterations of their
      electrophysiological and mechanical activities. These modifications, maximal 15
      17 min after the addition of lipid hydroperoxide, were completely abolished by
      S12340 (30 microM).

PMID- 8293792
TI  - Chronic prenatal and postnatal Pb2+ exposure increases [3H]MK801 binding sites in
      adult rat forebrain.
AB  - We have measured the binding of [3H]MK801 to the N-methyl-D-aspartate (NMDA)
      receptor-ion channel in membrane preparations from adult rat forebrain exposed to
      lead (Pb2+) during gestation, lactation, and postweaning. Our results indicate a
      30.9% increase in the number of [3H]MK801 binding sites in Pb2+ exposed animals
      relative to controls. No significant changes in the affinity constant were
      observed. The level of blood Pb2+ for which such changes were measured was 13.9
      +/- 2.8 micrograms/dl. These results indicate that alterations in the NMDA
      receptor-ion channel complex are present at blood Pb2+ levels which are
      environmentally relevant and suggest that chronic Pb2+ exposure during
      development can influence the NMDA receptor complex in the adult rat brain.

PMID- 8293793
TI  - Toluene diisocyanate-stimulated release of arachidonic acid metabolites in the
      organ bath from guinea-pig airways.
AB  - This study was designed to evaluate whether metabolites of arachidonic acid play
      a role in the contractile response to toluene diisocyanate in isolated guinea pig
      airways. In control experiments we collected the supernatant from an organ bath
      over a time period of 2 h, after the addition of toluene diisocyanate (100 and
      300 microM), and after the addition of toluene diisocyanate (300 microM) in the
      presence of indomethacin (5 microM). We measured prostaglandin E2, 6-keto
      prostaglandin F1 alpha, prostaglandin F2 alpha, thromboxane B2, leukotriene B4,
      leukotriene C4/D4/E4/F4 by radioimmunoassays. Levels of prostaglandin F2 alpha
      and 6-keto-prostaglandin F1 alpha increased significantly after addition of
      toluene diisocyanate in the absence of indomethacin. These results suggest that
      prostaglandins are involved in toluene diisocyanate-induced contractions in
      guinea-pig airways.

PMID- 8293794
TI  - HIV discovery: the final decision?

PMID- 8293795
TI  - Ethical principles and guidelines for experiments on animals. Swiss Academy of
      Medical Sciences and Swiss Academy of Sciences.

PMID- 8293796
TI  - Nematodes and the spleen: an immunological relationship.
AB  - Despite being a major organ of the immune system, the spleen's role in resisting,
      controlling or simply ameliorating nematode infections has been neglected. A
      review of both filarial and gastrointestinal nematodes suggests that though it is
      difficult to fully assess or quantify the organ's importance in vivo, the spleen
      is prominent in acting against nematode parasites in mammals. One manifestation
      of this is that transfer of lymphocytes from the spleen of immunised individuals
      can protect recipients against the disease. Expansion of splenic lymphoid tissue
      also alludes to its activity during nematode infection. There is a considerable
      need for investigation of the spleen under natural conditions as well as much
      more rigorously controlled experiments even in mammals besides birds and other
      vertebrates.

PMID- 8293798
TI  - Hemoglobin catabolism and the killing of intraerythrocytic Plasmodium falciparum
      by chloroquine.
AB  - To evaluate how chloroquine kills malaria parasites, hemoglobin catabolism was
      studied at the various stages of intraerythrocytic parasite development. We found
      that hemoglobin catabolism is switched off when Plasmodium falciparum parasites
      mature to the late trophozoite or early schizont stages and is switched on again
      during the ring stage. When hemoglobin catabolism is switched off, the parasites
      are resistant to the morphologic effects of chloroquine. Although the ring stage
      parasites failed to mature in the presence of chloroquine, some of them switched
      on hemoglobin ingestion and became stuffed with hemoglobin-filled vesicles,
      indicating a distal block in catabolism. In fact, we demonstrated a high-grade
      block in hemozoin production during a 22 h incubation of synchronized ring forms;
      ferriprotoporphyrin IX (FP) incorporation into the beta-hematin of hemozoin
      decreased from 900 to 50 pmol/10(6) parasitized erythrocytes. We propose that the
      primary effect of chloroquine on hemoglobin catabolism is to block FP
      polymerization to beta-hematin. Secondarily, toxic FP and FP-chloroquine
      complexes accumulate and are available to exert their several toxicities, which
      include inhibition of hemoglobin-degrading proteases and membrane damage. As a
      consequence, maturation is arrested and eventually the parasites die and lyse.

PMID- 8293797
TI  - The antimitotic drug 4,6-dimethyl-2-amino-3,4,5- trimethoxyphenyl-pyrimidine
      inhibits the nucleoside transport system of cells from various animal species.
AB  - 4,6-dimethyl-2-amino-3,4,5-trimethoxyphenyl-pyrimidine (B-31) is a pyrimidine
      derivative previously reported to arrest the mitotic cycle of mammalian cells in
      metaphase. In the present study it is shown that B-31 also acts as a specific
      inhibitor of the cellular uptake of nucleosides. The uptake of purinic and
      pyrimidinic nucleosides is inhibited by 80-90% at concentrations in the range 5
      20 micrograms/ml, whereas those of nucleobases, leucine, choline and glucose are
      unaltered at the maximum nontoxic dose of B-31 (25 micrograms/ml). Various
      mammalian (human, monkey and murine) and avian cell are equally sensitive to the
      inhibition of nucleoside transport. The antimitotic effect of B-31, by contrast,
      is species-specific: human cells are the most sensitive whereas monkey and
      chicken fibroblasts appear resistant to this effect. Both effects can be reversed
      by removal of B-31 from the medium; inhibition of nucleoside transport can also
      be reversed by high doses of the nucleosides themselves.

PMID- 8293799
TI  - Leukocyte mobilization from the guinea pig spleen by muscarinic cholinergic
      stimulation.
AB  - Important interactions between the immune system and the nervous and endocrine
      systems have become increasingly accepted. The present results demonstrate that
      the cholinergic agonist carbacholine greatly increased the number of granulocytes
      and lymphocytes in the splenic venous blood, but not arterial blood, shortly
      after administration to guinea pigs. The effect was largely blocked by
      pretreatment with atropine. In contrast, animals treated with indomethacin had a
      decreased number of leukocytes in both splenic venous and arterial blood. A
      decrease in relative splenic weight due to carbacholine treatment was also
      blocked by atropine. However, cholinergic leukocyte mobilization, or that
      previously observed after adrenergic stimulation, may not be caused by capsule
      contraction since it is not accompanied by mobilization of erythrocytes.
      Furthermore, indomethacin, which potentiates the response of splenic smooth
      muscle to adrenergic stimuli, blocked the effect of noradrenaline (NA) on
      leukocyte mobilization.

PMID- 8293800
TI  - Vanadium induced hemolysis of vitamin E deficient erythrocytes in Hepes buffer.
AB  - Several vanadium compounds were tested for their ability to induce in vitro
      hemolysis of vitamin E-deficient hamster erythrocytes. Free vanadyl caused
      hemolysis in Hepes buffer but not in Tris or phosphate buffer, while hemolysis
      was inhibited by catalase, chelators such as deferoxamine mesylate and EDTA, and
      hydroxyl radical scavengers such as ethanol and D-mannitol. Although metavanadate
      itself could not induce hemolysis, metavanadate with NAD(P)H caused hemolysis in
      Hepes buffer only, and superoxide dismutase prevented it. Hydrogen peroxide,
      hydroxyl radical and Hepes radical were involved in vanadyl-induced hemolysis,
      superoxide anion was further involved in metavanadate plus NAD(P)H-induced
      hemolysis. Vitamin E prevented hemolysis under both conditions.

PMID- 8293801
TI  - Retention of B. burgdorferi pathogenicity and infectivity after multiple passages
      in a co-culture system.
AB  - In vitro cultivation of B. burgdorferi in BSK medium results in the loss of
      infectivity and pathogenicity after repeated passages. To prevent this loss, a
      feeder layer of tibio-tarsal joint tissue derived from newborn LEW/N rats was
      grown on Cytodex 3 microcarriers in ESG (formerly BSKE), a novel medium developed
      to support the growth of both the feeder layer and B. burgdorferi. A new
      pathogenic isolate (FNJ) and a high passage, non-pathogenic strain (TNJ) grew
      well in this co-culture system with high yields of viable organism. FNJ caused no
      growth inhibition or visible damage to the cells in the feeder layer. FNJ
      remained arthritogenic for newborn LEW/N rats after 22 passages in the co-culture
      system, but lost its arthritogenicity after 7 passages when cultured in BSK
      medium. This borrelia-mammalian tissue co-culture technique presents an
      experimental system to study the long term interactions of B. burgdorferi with
      the infected host tissues in vitro, as well as facilitate diagnostic tests and
      vaccine development.

PMID- 8293802
TI  - Naja siamensis, a cryptic species of venomous snake revealed by mtDNA sequencing.
AB  - Because of possible variation in venom composition, an understanding of venomous
      snake systematics is of great importance for the optimization of antivenom
      treatment of snakebite patients. Intraspecific variation in the morphology of
      many venomous snakes complicates the definition and identification of some
      species when allopatric populations are involved. Selectively neutral or near
      neutral mtDNA sequences can reveal evolutionary relationships obscured by
      ecogenetically-caused morphological variation. We use comparative sequencing of
      the cytochrome oxidase subunit 1 gene to reveal the existence of a widespread,
      cryptic species of spitting cobra from southeast Asia. This species, Naja
      siamensis, is widely sympatric with other Asiatic cobra species. This may be of
      considerable medical significance, and calls for further research into venom
      composition in Asiatic cobras.

PMID- 8293803
TI  - Comparison of the binding sites of plant ferredoxin for two ferredoxin-dependent
      enzymes.
AB  - Differential chemical modification of acidic residues was used to map the binding
      site of plant ferredoxin (Fd) for the chloroplast enzyme ferredoxin:thioredoxin
      reductase (FTR). Binding of FTR to Fd inhibits chemical modification of Fd
      residues D34, D65, E92, E93, E94 and C-terminal A97. The binding site demarcated
      by these residues differs from that for ferredoxin:NADP+ reductase (FNR). The FTR
      site includes C-terminal residues but not helix 24-31, which is part of the FNR
      site. Both sites enclose the [2Fe-2S] cluster.

PMID- 8293804
TI  - Spectral and thermodynamic properties of the two hemes of the D1D2cytochrome b
      559 complex of spinach.
AB  - In agreement with previous work [Shuvalov, Heber and Schreiber (1988) FEBS Lett.
      258, 27-31] two hemes (low potential (LP) and extra low potential (XLP)) per two
      pheophytins were found in isolated D1D2Cyt b-559 complexes. Reductive and
      oxidative redox titrations demonstrate that the Em of the LP form is at about
      +150 mV. It is independent of pH between pH 7.2 and 9.4. The XLP heme is
      autoxidizable at pH 7.2 and displays, at this pH, an Em of -45 mV. Both the LP
      and XLP hemes show absorption peaks at 559 nm. They are proposed to have bis
      histidine ligation of the heme iron. At pH 9.4, the XLP heme splits into two
      forms. One of them has an Em of +40 mV, and absorption peaks at 559 nm showing
      the bis-histidine ligation. The other displays an Em of -220 mV and the peak is
      shifted to 562 nm. This last form is proposed to be due to the incorporation of
      OH- which occupies the 6th coordination position of the heme Fe(III) at high pH.
      The pK value for the conversion of the XLP heme is close to 7.7. In a structure
      simulation of the alpha-helices of alpha- and beta-polypeptide, the beta
      polypeptide, but not the alpha-polypeptide, reveals a distance between the
      histidine N and the heme Fe which permits stable N-Fe coordination. In the alpha
      polypeptide, OH- can be incorporated between N and Fe. The functional role of the
      two hemes of cyt b-559 is briefly discussed with respect to water oxidation and
      cyclic electron transfer.

PMID- 8293805
TI  - Trypsin induces Ca(2+)-activated Cl- currents in X. laevis oocytes.
AB  - The protease trypsin induces Ca(2+)-activated Cl- currents when applied in
      concentrations as low as 0.1 mg/ml to defolliculated, voltage clamped X. laevis
      oocytes. The response is dose-dependent and specific, as other proteases
      (chymotrypsin, Lys-C and Arg-C), or trypsin pretreated with soybean trypsin
      inhibitor, did not induce currents. Intracellular trypsin injection did not
      induce responses. The current does not appear to result from proteolytic
      activation of the endogenous receptor for lysophosphatidic acid, the only known
      Ca(2+)-mobilizing receptor consistently present in oocytes. These results suggest
      the presence on the oocyte membrane of a specific receptor for trypsin.

PMID- 8293806
TI  - The 20S proteasome mediates the degradation of mouse and yeast ornithine
      decarboxylase in yeast cells.
AB  - Ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, is
      one of the most rapidly degraded proteins in mammalian cells. Recently it has
      been demonstrated that mammalian ODC is degraded in vitro by the 26S protease
      that contains the 20S proteasome as its catalytic core, in a reaction that does
      not require ubiquitin. Here, we show that yeast and mouse ODC are both rapidly
      degraded in yeast cells and that their degradation severely inhibited in a mutant
      yeast cell line defective in the chymotryptic activity of proteinase yscE, the
      yeast 20S proteasome. These results provide compelling genetic support to
      previous biochemical studies suggesting the involvement of the 20S proteasome in
      the degradation of ornithine decarboxylase.

PMID- 8293807
TI  - Calcium sensing by human medullary thyroid carcinoma cells.
AB  - Regulation of the cytoplasmic calcium concentration ([Ca2+]i) was studied in fura
      2-loaded C-cells from two human medullary thyroid carcinomas (MTC). K+
      depolarization induced sustained rise of [Ca2+]i reversed by verapamil. Elevation
      of external Ca2+ from 0.5 to 3.0 mM triggered regular oscillations or steady
      state increases of [Ca2+]i. In Ca(2+)-deficient medium Sr2+ caused steady-state
      increase or oscillations of the 340/380 nm fluorescence ratio. The Ca2+ and Sr2+
      actions were partially reversible by verapamil. La3+ and Ce3+ elicited transient
      [Ca2+]i peaks independent of external Ca2+, but no oscillations. The results
      indicate that human MTC cells express a parathyroid-like Ca2+ sensor coupled to
      intracellular mobilization and influx of Ca2+. A voltage-dependent Ca2+ influx
      may be of importance for the oscillations of [Ca2+]i.

PMID- 8293808
TI  - 1 alpha-hydroxyvitamin D3 inhibits type II collagen-induced arthritis in rats.
AB  - The effects of 1 alpha-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 on Type II
      collagen-induced arthritis in rats, an experimental model of rheumatoid
      arthritis, were examined. Oral administration of 1 alpha-hydroxyvitamin D3
      significantly suppressed the incidence of arthritis and inhibited hind paw
      swelling. The level of anti-Type II collagen antibodies was decreased in the 1
      alpha-hydroxyvitamin D3 treated-group. In contrast, 24,25-dihydroxyvitamin D3,
      indomethacin, and gold had no effect on either the incidence of arthritis or the
      antibody levels. These findings demonstrate a beneficial effect of 1 alpha
      hydroxyvitamin D3 on Type II collagen-induced arthritis in rats and indicate that
      it has an antirheumatic effect.

PMID- 8293809
TI  - Phospholipase D activity of isolated rat brain plasma membranes.
AB  - With [14C]oleate-labeled phosphatidylcholine as a substrate for phospholipase D
      the hydrolytic activity was measured by phosphatidic acid formation and the
      transphosphatidylation activity was measured by the phosphatidylethanol formed in
      the presence of ethanol. The pH optimum was 6.5 with dimethylglutarate as the
      buffer. EGTA inhibited the transphosphatidylation activity to a greater extent
      than the hydrolytic activity. In contrast CaCl2, BaCl2, MgCl2 and SrCl2
      stimulated the hydrolytic activity without effecting the transphosphatidylation
      activity. BeCl2 another member of the group IIa transition metals was a very
      potent inhibitor of both the hydrolytic and transphophatidylation activity. GTP
      gamma S, an activator of G protein-mediated events, was an inhibitor of both
      activities.

PMID- 8293810
TI  - Escherichia coli PII protein: purification, crystallization and oligomeric
      structure.
AB  - The Escherichia coli signal transduction protein PII, product of the glnB gene,
      was overproduced and purified. The predicted molecular weight of the protein
      based on the correct nucleotide sequence is 12,427 and is very close to the value
      12,435 obtained by matrix-assisted laser desorption mass spectrometry. Hexagonal
      crystals of the unuridylylated form of PII with dimensions 0.2 x 0.2 x 0.3 mm
      were grown and analysed by X-ray diffraction. The crystals belong to space group
      P6(3) with a = b = 61.6 A, c = 56.3 A and Vm of 2.5 for one subunit in the
      asymmetric unit. A low-resolution electron density map showed electron density
      concentrated around a three-fold axis, suggesting the molecule to be a trimer. A
      sedimentation equilibrium experiment of the meniscus depletion type was used to
      estimate a molecular weight of 35,000 +/- 1,000 for PII in solution. This result
      is consistent with the native protein being a homotrimer.

PMID- 8293811
TI  - Does a synthetic peptide containing the leucine-zipper domain of c-myb form an
      alpha-helical structure in solution?
AB  - We have examined a synthetic peptide containing the putative leucine zipper
      domain of the chicken c-myb proto-oncogene using circular dichroism (CD)
      spectroscopy. The peptide adopts an alpha-helical structure only at low
      temperatures and in the presence 2,2,2-trifluoroethanol.

PMID- 8293812
TI  - Red edge excitation shifts of crystallins and intact lenses. A study of segmental
      mobility and inter-protein interactions.
AB  - The shift that occurs in the fluorescence emission wavelength upon changing the
      excitation wavelength towards the red edge of the absorption band is termed red
      edge excitation shift (REES). We have monitored the REES of intrinsic protein
      fluorescence of freshly isolated intact lenses, of individual crystallins in
      their native, denatured and photodamaged states and also of crystallin mixtures.
      The observed REES values for the lenses from different species are different
      suggesting that the mobilities and packing of the crystallins may vary with the
      species. Lens photodamage in all the cases resulted in an increase of REES.
      Denaturation of crystallins in solution reduces REES and renaturation restores
      it. Mixtures of alpha- and beta-crystallins prepared either by directly mixing
      equimolar solutions or mixing them in 4 M urea followed by dialysis
      (reconstituting) gave similar REES values indicating the absence of any specific
      interactions in dilute solutions. Possible existence of induced alterations
      facilitating inter-crystallin interactions at high protein concentration is
      suggested.

PMID- 8293813
TI  - Small GTP-binding proteins of squid photoreceptor. Interaction with
      photoactivated rhodopsin.
AB  - Squid photoreceptor membranes contain several small GTP-binding proteins (22-27
      kDa) in addition to heterotrimeric G-proteins. In addition, these membranes
      contain several proteins which can be ADP-ribosylated by exoenzyme C3 from
      Clostridium botulinum (C3). These proteins are similar but not identical to C3
      substrates from bovine rod outer segments. It is shown that substrates of C3 in
      squid photoreceptor interact with rhodopsin in a light-dependent manner. These
      data suggest involvement of small GTP-binding proteins in phototransduction
      processes in invertebrates.

PMID- 8293814
TI  - Anaesthetic phencyclidine, blocker of the ATP-sensitive potassium channels.
AB  - The double sucrose gap and patch-clamp studies revealed that phencyclidine
      blocked the ATP-sensitive K+ channel in isolated cardiac cells (half-maximal
      inhibition at approximately 20 microM; Hill coefficient approximately 1). 10
      microM phencyclidine increased the inward Ca2+ current and blocked the outward K+
      current in the frog auricle trabeculae. The phencyclidine effects on the frog
      auricle trabeculae and the isolated cardiac cells proved to be quite reversible.

PMID- 8293815
TI  - Affinity purification of GTPase proteins from oat root plasma membranes using
      biotinylated GTP.
AB  - Biotinylated GTP was synthesized and it was demonstrated that this ligand was bi
      functional: it competed with [3H]Gpp(NH)p for binding to membrane proteins and it
      bound to immobilized avidin. Peripheral plasma membrane proteins were solubilized
      in a low-salt wash, incubated with GTP-biotin and biotinylated proteins were
      coupled to an avidin column. Elution with excess biotin yielded 10 polypeptides
      as seen with a silver stained SDS-PAGE gel. Antisera raised against Ras, a small
      GTPase, strongly interacted with three proteins with MW of 38, 27 and 25 kDa and
      also with 6 other proteins. G alpha-common antibodies interacted with proteins of
      MW = 66 and 38 kDa. This method enables the rapid purification of GTP-binding
      proteins and opens the possibility to assign a role to specific GTPases in signal
      transduction pathways.

PMID- 8293816
TI  - Tissue specific membrane association of alpha 1T, a truncated form of the alpha 1
      subunit of the Na pump.
AB  - We have assessed the Na pump alpha-subunit isoform content utilizing site
      directed antibodies in two vascular smooth muscle (VSM) preparations known to
      contain functional Na pump sites, VSM microsomal fractions (Na+, K(+)-ATPase) and
      intact primary confluent cells (ouabain inhibited 86Rb uptake). A comparison of
      isoform content was made with kidney microsomes. Both VSM and kidney microsomes
      contained a full length alpha 1 subunit (approximately 100 kDa) as well as a
      truncated subunit, alpha 1T (approximately 66 kDa). SDS treatment of VSM
      microsomes effected an increase in Na+, K(+)-ATPase and a retention of alpha 1T.
      SDS treated kidney microsomes retained the alpha 1 isoform and Na+, K(+)-ATPase.
      Confluent VSM cells showed no detectable alpha 1, only alpha 1T. In the absence
      of detectable full length alpha 1, the alpha 1T protein may represent a
      functional Na pump component in canine VSM.

PMID- 8293817
TI  - The novel hexapeptide motif found in the acyltransferases LpxA and LpxD of lipid
      A biosynthesis is conserved in various bacteria.
AB  - Two bacterial acyltransferases (LpxA of Escherichia coli, LpxD of E. coli and
      Salmonella typhimurium) have previously been shown to consist of a very unusual
      tandem-repeat structure with tens of repeating hexapeptides (24 hexapeptides in
      LpxA, 26 in LpxD). By sequencing LpxD of Yersinia enterocolitica (a distant
      relative of E. coli and S. typhimurium within Enterobacteriaceae) as well as LpxA
      of S. typhimurium and Y. enterocolitica, and by analyzing the existing data on
      these enzymes of Ricketsia rickettsii, it was now shown that the hexapeptide
      repeat pattern is a very conservative property of these enzymes. Even though the
      overall homology (allowing equivalent amino acids) between the four proteins was
      only 59% in LpxA and 58% in LpxD, the homology in the first residue of each
      hexapeptide was 87% in LpxA and 100% in LpxD. Secondary structure prediction by
      PredictProtein server suggested a very strong beta strand dominance in all the
      hexad regions. Accordingly, LpxA and LpxD of various bacterial origins can now be
      regarded as structurally very unusual enzymes, largely consisting of hexad
      repeats.

PMID- 8293818
TI  - Trypanosoma cruzi epimastigote forms possess a Ca(2+)-calmodulin dependent
      protein kinase.
AB  - Trypanosoma cruzi epimastigote forms showed a tightly bound Ca(2+)-calmodulin
      dependent protein kinase activity, which could be partially extracted from
      membranes and axonemes. The enzyme is constituted by subunits which were
      autophosphorylated in the absence of exogenous substrates. An antibody against
      CaM kinase II recognized a Ca(2+)- or Ca(2+)-CaM-dependent conformational epitope
      in these fractions. The detected bands were of molecular weights similar to the
      alpha and beta subunits of the corresponding bovine brain enzyme (60 and 50 kDa).
      Studies using [125I]CaM revealed the presence of a CaM-binding domain. These
      experiments confirm that the parasite possesses a particulate CaM kinase with
      characteristics similar to the bovine brain enzyme.

PMID- 8293819
TI  - Succinic acid monomethyl ester protects rat pancreatic islet secretory potential
      against interleukin-1 beta (IL-1 beta) without affecting glutamate decarboxylase
      expression or nitric oxide production.
AB  - Rat pancreatic islets exposed to interleukin-1 beta (IL-1 beta) in the presence
      of succinic acid monomethyl ester (SAM) have a higher insulin release in response
      to glucose and higher glucose oxidation rates, as compared to islets exposed to
      IL-1 beta alone. These beneficial effects of SAM were not accompanied by any
      decrease in IL-1 beta-induced nitric oxide (NO) production nor inhibition of
      aconitase activity. Moreover, SAM did not increase biosynthesis of glutamate
      decarboxylase. SAM apparently improves beta-cell function mostly by increasing
      the capacity of these cells to endure NO exposure and partial blockage of the
      Krebs cycle.

PMID- 8293820
TI  - Chemical synthesis and biological activity of a novel antibacterial peptide
      deduced from a pig myeloid cDNA.
AB  - Several myeloid precursors of antibacterial peptides have recently been shown to
      share homologous pre- and pro-regions. Taking advantage of this homology, a novel
      cDNA was cloned from pig bone marrow RNA. This encodes a 166-residue polypeptide
      with highly conserved pre- (29 residues) and pro- (101 residues) sequences,
      followed by a unique, 36-residue C-terminal sequence. Structure analyses of this
      C-terminal region have identified a highly cationic sequence predicted to adopt
      an amphipathic alpha-helical conformation. A peptide corresponding to this
      sequence was chemically synthesized and shown to arrest the growth of both Gram
      positive and Gram-negative bacteria. At least for Escherichia coli, the activity
      of this peptide appears to be mediated by its ability to permeabilize the
      bacterial membranes.

PMID- 8293821
TI  - New virus-specific T-helper epitopes of foot-and-mouth disease viral VP1 protein.

PMID- 8293822
TI  - A randomized study of transcervical intrafallopian transfer of pronucleate
      embryos controlled by ultrasound versus intrauterine transfer of four- to eight
      cell embryos.
AB  - OBJECTIVE: To establish the value of transcervical intrafallopian transfer of
      zygotes and the accuracy of fallopian cannulation. DESIGN: A prospective
      randomized study, comparing ultrasonically controlled transcervical
      intrafallopian transfer of zygotes with intrauterine transfer of cleaved embryos.
      SETTING: Department of IVF of the Rotterdam Academic Hospital. PATIENTS: One
      hundred forty-five patients with patent tubes entered the IVF program. MAIN
      OUTCOME MEASURE: Pregnancy rates in both groups and ultrasound (US) assessment
      during fallopian cannulation and ET. RESULTS: Transvaginal cannulation of the
      tube appears not to be sufficiently accurate when performed without US guidance.
      Catheter damage occurred in many cases. The previously reported superior
      implantation rate after intrafallopian transfer in comparison with intrauterine
      transfer could not be confirmed. CONCLUSIONS: Intrauterine transfer of cleaved
      embryos remains the method of choice in IVF.

PMID- 8293823
TI  - The combination of coculture and selective assisted hatching: results from their
      clinical application.
AB  - OBJECTIVE: To establish pregnancies using a combination of coculture and
      selective assisted hatching. DESIGN: Clinical application for a selected group of
      patients. Not a controlled study. SETTING: Private infertility practice.
      PATIENTS: Women with high basal FSH levels, ovulatory disorders, and multiple
      failed IVF attempts. MAIN OUTCOME MEASURES: Pregnancy and implantation rates.
      RESULTS: Of the 95 patients who had coculture and selective assisted hatching, 45
      (47.0%) have an ongoing pregnancy with a 23.0% implantation rate. CONCLUSION: The
      combination of coculture and assisted hatching produced acceptable pregnancy and
      implantation rates within the selected patient population.

PMID- 8293824
TI  - Sex determination of human embryos using the polymerase chain reaction and
      confirmation by fluorescence in situ hybridization.
AB  - OBJECTIVE: To use fluorescence in situ hybridization to corroborate the
      polymerase chain reaction (PCR) preimplantation diagnosis of human embryos in
      three couples carrying a chromosome X-linked disease. SETTING: Clinical and
      research IVF laboratories. PATIENTS: Individuals undergoing preimplantation
      diagnosis. RESULTS: Four ETs were performed in couples undergoing preimplantation
      diagnosis by multiplex PCR or fluorescence in situ hybridization, resulting in
      the birth of two normal female twins. The result of another is pending. A total
      of 22 embryos were analyzed by PCR. Embryos that were diagnosed as being at risk
      of carrying the genetic abnormality (n = 8), embryos that failed diagnosis (n =
      4), and genetically normal embryos that arrested development (n = 4) were further
      analyzed by fluorescence in situ hybridization. The sex of all 16 embryos was
      determined and confirmed the previous 12 preimplantation diagnoses by multiplex
      PCR. In addition, fluorescence in situ hybridization analysis allowed the
      detection of two aneuploid embryos, one XO and one XXY, previously diagnosed by
      PCR as a normal female and male. Two mosaics were also detected. CONCLUSION:
      Polymerase chain reaction and fluorescence in situ hybridization are possible for
      preimplantation sex determination in cases of genetic sex-linked disease.
      Fluorescence in situ hybridization, however, supplies additional information
      about sex chromosome aneuploidy and is not susceptible to contamination or
      misdiagnosis of monosomy X.

PMID- 8293825
TI  - Subzonal insertion of multiple sperm is a treatment for male factor infertility.
AB  - OBJECTIVE: To determine whether subzonal insemination of multiple sperm is an
      effective treatment for male factor infertility. DESIGN: Subzonal insemination by
      micromanipulation of sperm and oocytes for male factor patients. PATIENTS: Two
      hundred eight patients were selected on previous fertilization history and/or
      semen parameters. They could be assigned to one of three groups: group A had
      previous IVF failure, group B had a low fertilization rate with previous IVF, and
      group C had insufficient sperm for IVF. INTERVENTIONS: Oocytes were inseminated
      by subzonal insertion of multiple sperm. MAIN OUTCOME MEASURES: Fertilization and
      pregnancy rates. RESULTS: There have been 208 patients treated through 332
      treatment cycles. Of 2,789 oocytes inseminated, 784 oocytes were fertilized (28%)
      and 516 of these (66%) were monospermic. This represents normal fertilization in
      207 cycles (62% of total patient cycles). These 207 cycles produced an average of
      2.6 +/- 1.8 embryos. The resultant 487 embryos were either transferred or
      cryopreserved for future transfer. A total of 42 pregnancies (21% per ET)
      resulted from 200 ET procedures with 397 embryos. Miscarriages or elective
      terminations have occurred (11/42 pregnancies, 26% to date) and 21 deliveries
      have resulted in 26 babies. There are nine ongoing pregnancies. Three of the
      pregnancies have been from cryopreserved embryos. Group B patients had the
      highest fertilization rate (23%) but the lowest pregnancy rate (7%). No other
      significant relationships between patient group and outcome were found.
      CONCLUSIONS: Subzonal insemination of multiple sperm is an effective treatment
      for some forms of male factor infertility.

PMID- 8293826
TI  - Salivary excretory pattern of testosterone in substitutive therapy with
      testosterone enanthate.
AB  - OBJECTIVE: To determine salivary and serum T levels by an RIA method after a
      single injection of 250 mg IM of commercially available T enanthate. DESIGN:
      Research study. SETTING: Patients attended in a hospital environment. PATIENTS:
      Sixteen men with secondary hypogonadism. INTERVENTIONS: Testosterone enanthate
      was administered, and salivary samples were taken before the injection.
      Thereafter, these samples were obtained daily until day 7 and then on alternate
      days until day 28 after injection. Blood samples were taken previously and after
      the injection (5 samples during the month). MAIN OUTCOME MEASURE: Salivary and
      serum T. RESULTS: Salivary T levels rose from 3.46 +/- 3.16 to 13.82 +/- 7.78
      ng/100 mL (0.12 +/- 0.11 to 0.48 +/- 0.27 nmol/L) within 24 hours and remained in
      that range until day 7. From day 9, 7.20 +/- 2.88 ng/100 mL (0.25 +/- 0.10
      nmol/L), a progressive decrease of these values was observed until day 14: 5.18
      +/- 2.88 ng/100 mL (0.18 +/- 0.10 nmol/L). From day 16 until day 28, salivary
      concentrations returned to hypogonadal levels. CONCLUSION: We conclude that T
      salivary concentrations may be applied to assess the effectiveness of T
      substitutive therapy in hypogonadal men and could replace serum in the monitoring
      of this type of therapy.

PMID- 8293827
TI  - Identification of a transforming growth factor alpha-like molecule in human
      seminal plasma.
AB  - OBJECTIVE: To characterize the putative seminal growth promoting factor
      serendipitously observed when human seminal plasma was analyzed for bioactive
      FSH. DESIGN: A pool of human seminal plasma was subjected to sequential Sephadex
      G-75 (superfine) chromatography and high-performance size exclusion liquid
      chromatography. The fractions were tested for mitogenic activity using a rat
      granulosa cell assay and normal rat kidney (NRK) cells. Properties of the factor
      were established and characterization by gel electrophoresis and neutralization
      with antibody were accomplished. SETTING: Reproductive Biology Research
      Laboratory at McMaster University Medical Centre. MAIN OUTCOME MEASURES: Ability
      of purified fractions of human seminal plasma to augment the uptake of tritiated
      thymidine into cell DNA. RESULTS: Mitogenic activity of human seminal plasma was
      augmented in the presence of FSH but not hCG, PRL, E2, T, P, or
      dihydrotestosterone. The putative growth factor synergized with insulin-like
      growth factor I (IGF-I), epidermal growth factor (EGF), and transforming growth
      factor beta (TGF-beta) but not with TGF-alpha. Mitogenic activity was neutralized
      by a specific TGF-alpha antibody in a dose-dependent manner. The molecular weight
      of the factor as assessed by gel electrophoresis is 6 kd. CONCLUSIONS: Human
      seminal plasma contains a mitogen that is similar to TGF-alpha.

PMID- 8293828
TI  - Creatine kinase immunocytochemistry of human sperm-hemizona complexes: selective
      binding of sperm with mature creatine kinase-staining pattern.
AB  - OBJECTIVE: To examine the clinical significance of the increased sperm
      cytoplasmic content that is due to a fault of spermatogenesis, we have further
      studied the relationship between increased sperm creatine kinase (CK)
      concentrations and diminished fertilizing potential in men. In the present work,
      we used CK immunocytochemistry of human sperm-hemizona (HZ) complexes to examine
      whether the distribution of mature (clear heads), intermediate (sperm heads with
      light stippling), and immature (heads with heavy stippling or with solid CK
      staining) spermatozoa bound to the HZ would follow the incidence of these sperm
      in the samples tested, or if there is a preferential binding by the mature sperm.
      DESIGN: Two pairs of HZ were exposed to washed semen and to their swim-up sperm
      fractions. The sperm and sperm-HZ complexes were treated with a CK antibody
      followed by horseradish peroxidase immunostaining, and the sperm were evaluated
      for maturity. SETTING: Men presenting for fertility evaluation were studied in
      two university-based andrology laboratories. RESULTS: The binding of the HZ was
      selective for mature sperm as indicated by the incidence of intermediate and
      immature sperm in washed semen versus bound to the HZ (intermediate: 20.0% versus
      1.4%; immature: 7.6% versus 0.5% [mean +/- SEM]) or in swim-up sperm fractions
      versus the HZ (intermediate: 18.7% versus 3.4%; immature: 2.5% versus 0.2%). The
      binding was almost exclusive to normal sperm (96.4% to 98.1%) whether the HZ were
      exposed to washed semen or swim-up fractions in spite of the five to ten times
      higher incidence of intermediate and immature sperm. CONCLUSIONS: Mature sperm
      selectively bind to the zona. We suggest that spermatozoa with immature CK
      staining patterns are deficient in the site(s) of oocyte recognition and binding.

PMID- 8293829
TI  - Comparison of flow cytometric measurement of seminal antisperm antibodies with
      the mixed antiglobulin reaction and the serum tray agglutination test.
AB  - OBJECTIVE: To compare the mixed antiglobulin reaction (MAR) and the serum tray
      agglutination test (TAT) with the flow cytometric (FCM) measurement of sperm
      antibodies. To evaluate by FCM the correlation in sperm antibody parameters
      between paired semen ejaculates obtained 2 to 4 weeks apart and the effect of
      washing on sperm antibody levels. SETTING: University-based infertility clinic.
      PATIENTS: The TAT and FCM were done on 81 patients with a positive immunoglobulin
      (Ig)G-MAR test. The correlation of sperm antibody parameters between paired semen
      samples was done in 16 men. A few samples were used to study the effect of
      washing on sperm antibody parameters. MAIN OUTCOME MEASURES: The proportion of
      spermatozoa positive for IgG and IgA antibodies as well as the number of antibody
      molecules per spermatozoa measured by FCM. RESULTS: In general, the degree of MAR
      positivity but not that of the TAT correlated with the sperm antibody load. With
      reference to FCM the MAR test had an 1% false positive rate, whereas the serum
      TAT had a 25% false negative rate. Correlation between FCM measurements of paired
      semen samples was good. Washing the spermatozoa once removed the loosely bound
      antibodies; further washes were not useful. CONCLUSION: Flow cytometry is a
      reliable technique that correlates with the MAR test. In patients with a strongly
      positive MAR, FCM is useful to identify patients with a low sperm antibody load.
      It is speculated that patients with a low sperm antibody load may respond better
      to IVF treatment.

PMID- 8293831
TI  - Office falloposcopic assessment in proximal tubal occlusive disease.
AB  - Intraluminal images were reliably obtained by office falloposcopy in the presence
      of proximal tubal occlusion. Although there were associations between data
      obtained at laparoscopy and intralumenal appearances, these relations were not
      uniform, indicating that there may be a role for falloposcopic assessment in
      planning the management of proximal tubal occlusion. A prospective study is
      advocated to assess the linear eversion catheter as a therapy for proximal tubal
      occlusion.

PMID- 8293830
TI  - Effects of the coculture with human endometrial cells on the function of
      spermatozoa from subfertile men.
AB  - OBJECTIVE: To evaluate the effects of a coculture with human endometrial cells on
      the function of spermatozoa from samples obtained from infertile couples. DESIGN:
      In a prospective study, human spermatozoa selected by swim-up from fresh samples
      were cultured on human endometrial feeder layers. Thereafter, their viability,
      motility, acrosome integrity, and ability to penetrate zona-free hamster oocytes
      were evaluated. Spermatozoa from the same samples incubated under the same
      conditions but in the absence of endometrial cells, as well as in the medium
      previously spent for cell culture, were used as controls. SETTING: Andrology
      Laboratory of the Infertility Center of San Raffaele Hospital. PATIENTS:
      Spermatozoa were obtained from 17 infertile men attending the Infertility Center
      at our hospital. RESULTS: Spermatozoa incubated in the presence of endometrial
      cell feeder layers did not differ from controls with regard to their viability or
      motility. Conversely, the percent spontaneous acrosome reactions after 18 hours
      of incubation was significantly higher for spermatozoa cocultured (19.7 +/- 2.2
      versus 11.2 +/- 1.9; mean +/- SE). The mean number of spermatozoa penetrating
      hamster oocytes was also significantly improved (1.24 +/- 0.3 versus 0.68 +/-
      0.24). This effect did not seem to be solely due to the secretion of soluble
      factors by endometrial cells in the medium, in that spermatozoa incubated in the
      medium spent for endometrial cell culture had a similar acrosome reaction
      percentage but a lower rate of hamster egg penetration. CONCLUSIONS: The
      coculture with human endometrial cells appeared to be beneficial for improving
      the sperm function. This effect partially may be due to the secretion of steroids
      in the medium, which increases the quota of spontaneous acrosome reaction and in
      part due to the direct contact of cells with spermatozoa, maybe for the
      detoxification of the medium or the release of trophic factors. Coculture might
      be a promising approach to preparing spermatozoa for assisted fertilization in
      cases of subfertile males.

PMID- 8293832
TI  - Live birth after treatment of severe adenomyosis with a gonadotropin-releasing
      hormone agonist.
AB  - A patient with a 10-year history of secondary infertility underwent GnRH-a
      therapy with LA for 5 months to control symptoms of severe adenomyosis and to
      avoid an unwanted hysterectomy. Shortly after cessation of treatment, the patient
      conceived. A healthy male was delivered at term by cesarean section, which makes
      this the first report of a live birth after treatment of severe adenomyosis with
      a GnRH-a.

PMID- 8293833
TI  - Leuprolide acetate treatment of catamenial pneumothorax.
AB  - A 35-year-old nulligravid female with a 20 pack year history of smoking and
      continuous OC use since age 16 presented with recurrent pneumothoraces coinciding
      with the onset of menses at age 28. At that time she underwent a right partial
      pleurectomy and lobectomy, which demonstrated bullous disease but no glandular or
      stromal elements. Although catamenial respiratory discomfort persisted while on
      OCs, no pneumothoraces were documented until age 33 at which time she was given
      the diagnosis of catamenial pneumothorax. A diagnostic laparoscopy failed to
      demonstrate endometriosis or the presence of diaphragmatic defects. In an effort
      to preserve her fertility, she began a course of LA-GnRH-a therapy with depot LA.
      Because of disabling vasomotor and emotional side effects, continuous conjugated
      estrogens and MPA acetate were given as add-back therapy. She has remained
      symptom and side effect free for over 2 years on this regimen.

PMID- 8293834
TI  - Bone density and endometriosis.
AB  - To establish whether there is evidence of low bone density in women with
      endometriosis, we compared bone density between 48 women with laparoscopically
      proven endometriosis and 48 age-matched normal controls. Bone density of the
      lumbar spine (L2-4), proximal femur (femoral neck, Ward's triangle, and
      trochanteric region), and total body were measured by dual energy roentgenogram
      absorptiometry. After adjusting for physical and lifestyle differences, bone
      density was not significantly different between the groups in any site. Bone
      density measurements were not related to the severity of endometriosis. These
      results do not confirm evidence of low bone density in women with endometriosis.

PMID- 8293835
TI  - Comparative study: Replens versus local estrogen in menopausal women.
AB  - This was an open-label study comparing effects of a nonhormonal drug-free
      bioadhesive vaginal moisturizer to a local estrogen therapy in the treatment of
      vaginal dryness symptoms. There were 15 women evaluated in each treatment group
      during a 12-week period. Results indicated that the bioadhesive vaginal
      moisturizer was a safe and effective alternative to estrogen vaginal cream, with
      both therapies exhibiting statistically significant increases in vaginal
      moisture, vaginal fluid volume, and vaginal elasticity with a return of the
      premenopausal pH state.

PMID- 8293836
TI  - How adequate is resident training in reproductive endocrinology and infertility?

PMID- 8293837
TI  - Laparoscopy diagnosis of chlamydial salpingitis using a tubal cytobrush.
AB  - This is a report of our nontraumatic technique using a tubal cytobrush for
      epithelial tubal cell recovery during laparoscopy diagnosis of C. trachomatis
      salpingitis. We performed a three-way laparoscopy in 95 women and inserted a long
      flexible fallopian tube brush through one of the trocars. This technique showed
      that it is possible to reach the infection site avoiding vaginal contamination
      and that sufficient tubal cells can be obtained for isolation of intracellular
      pathogens. The technique also allowed rapid antigen detection directly on tubal
      cells by IFA and C. trachomatis isolation on cell culture. Tubal scraping did not
      cause bleeding or adhesions as later observed in a matched group of women who
      underwent further laparoscopy during GIFT.

PMID- 8293838
TI  - A registry of single case reports!

PMID- 8293839
TI  - The fecundity gene for sheep and man.

PMID- 8293840
TI  - Predictive value of progesterone and estradiol levels for pregnancy.

PMID- 8293841
TI  - Extending the use of gonadotropin-releasing hormone agonists: the emerging role
      of steroidal and nonsteroidal agents.
AB  - OBJECTIVE: To review and summarize the state of the art as it relates to the long
      term application of GnRH agonists (GnRH-a). DESIGN: A retrospective analysis of
      the available literature and results and an up-to-date review of a rapidly
      evolving field. CONCLUSION: Although the precise use of long-term GnRH-a therapy
      (in conjunction with sex steroid add-back therapy) remains unknown, the
      information provided strongly supports additional studies in this area to achieve
      a body of promising preliminary data.

PMID- 8293842
TI  - Cigarette smoking and sperm density: a meta-analysis.
AB  - OBJECTIVE: To quantify, through meta-analysis techniques, the association between
      cigarette smoking and sperm density. METHODS: The logarithm of the ratio of mean
      sperm density for smokers to that for nonsmokers for the studies included in this
      meta-analysis was regressed against a constant, an indicator of study population
      source (infertility clinic patients or normal men), minimum number of cigarettes
      smoked per day among smokers (< 10, > or = 10), exclusion of azoospermic men
      (yes/no), number of semen specimens analyzed (one versus two), and blinding of
      laboratory personnel to the smoking status of the study participants (yes/no).
      Regression analyses were performed both unweighted and weighted inversely by
      study size. A qualitative and quantitative assessment of the relationship between
      the numbers of cigarettes smoked per day and sperm density was performed.
      RESULTS: Results of the meta-analysis indicate that smokers' sperm density is on
      average 13% to 17% (95% confidence interval = 8.0, 21.5) lower than that of
      nonsmokers. No other factors besides cigarette smoking were found to be
      independent predictors of sperm density. No clear dose-response relationships
      between the numbers of cigarettes smoked per day and sperm density emerged.
      Research conducted by the authors supports the findings of the meta-analysis.
      CONCLUSION: Cigarette smoking is associated with lowered sperm density. The
      inconsistency in the literature with regard to this conclusion appears to be the
      result of small sample sizes in most studies.

PMID- 8293843
TI  - The prediction of the chance to conceive in subfertile couples.
AB  - OBJECTIVE: To develop a model that can predict the chance to conceive
      spontaneously in subfertile couples. DESIGN: In a cohort study, a consecutive
      series of patients consulting infertility was followed up. We related information
      from previous history, physical examination, postcoital tests (PCT), semen
      analyses, and sperm penetration meter tests with the occurrence of a spontaneous
      pregnancy. SETTING: Fertility center in a university hospital. PATIENTS: Nine
      hundred ninety-six couples consulting for infertility due to cervical hostility,
      male subfertility, or unexplained infertility. INTERVENTIONS: None. MAIN OUTCOME
      MEASURE(S): Time between intake and occurrence of the first spontaneous
      pregnancy. RESULTS: Information from the previous history (duration of
      infertility, primary or secondary female infertility, age of the woman, fertility
      problems in male's family), the percentage motile sperm in the first semen
      analysis, and the result of the first PCT are sufficient to predict the chance to
      conceive. A pocket chart is presented for easy use of the model. CONCLUSIONS:
      With a limited amount of diagnostic information, the chance to conceive
      spontaneously can be predicted.

PMID- 8293844
TI  - Midluteal-phase vaginal color Doppler assessment of uterine artery impedance in a
      subfertile population.
AB  - OBJECTIVE: To compare the midluteal uterine artery impedance to blood flow as
      measured by the pulsatility index in women with different causes of infertility
      with that of women with normal fertility and to correlate this with endometrial
      thickness. DESIGN: A prospective study of normal women undergoing insemination
      with donor semen and subfertile women with tubal damage, endometriosis, premature
      ovarian failure, anovulation, or unexplained infertility. SETTING: A tertiary
      infertility center. PATIENTS: One-hundred sixty-one women (25 to 40 years of age)
      who were attending the clinic for subfertility treatment and 23 normal women who
      were having artificial insemination with donor sperm because their partners were
      azoospermic. INTERVENTIONS: All women were examined by transvaginal
      ultrasonography, with color flow imaging and blood flow analysis, on day 21 of an
      unstimulated ovarian cycle. MAIN OUTCOME MEASURES: The mean pulsatility index of
      the left and right uterine arteries and the endometrial thickness. RESULTS: The
      patients were grouped according to the causes of infertility and compared with
      normal women. There were 23 women in the normal group (median pulsatility index,
      1.91; range, 0.84 to 2.95), 35 with unexplained infertility (median pulsatility
      index, 2.45; range, 1.0 to 7.0), 91 with tubal damage (median pulsatility index,
      2.65; range, 1.25 to 8.0), 8 with endometriosis (median pulsatility index, 2.32;
      range, 2.05 to 5.7), and 22 with anovulatory infertility (median pulsatility
      index, 3.03; range, 1.6 to 7.0). All the infertile groups had significantly
      different median pulsatility indexes when compared with the normal group, and the
      pulsatility indexes correlated with endometrial thickness. CONCLUSIONS: The
      impedance to uterine artery blood flow is significantly different in women with
      different causes of infertility as compared with women of normal fertility.
      Increased resistance to uterine blood flow in the midluteal phase may be an
      important contributing factor to some causes of infertility and the cause of some
      previously "unexplained" infertility.

PMID- 8293845
TI  - Improved results in multifetal pregnancy reduction: a report of 72 cases.
AB  - OBJECTIVE: To evaluate pregnancy outcome after either transabdominal or
      transvaginal multifetal pregnancy reduction. DESIGN: A study of 72 consecutive
      multifetal pregnancy reductions. SETTING: Department of Obstetrics and
      Gynecology, The Chaim Sheba Medical Center Tel Hashomer, Israel. PATIENTS:
      Seventy-two patients with multifetal pregnancies: 2 twins, 27 triplets, 26
      quadruplets, 10 quintuplets, 3 sextuplets, 1 septuplet, 2 nontuplets, and one
      pregnancy with 12 fetuses. INTERVENTION: Multifetal pregnancy reduction was
      performed at 9 to 13 weeks' gestation by either transabdominal or transvaginal
      potassium chloride injection. MAIN OUTCOME MEASURES: Early and late complications
      related to the procedure, outcome of pregnancy, and comparison of two periods.
      RESULTS: Procedures performed between 1984 and 1989 (36 patients) were associated
      with a 33.3% pregnancy loss, whereas those performed between 1990 and 1992 (36
      patients) were associated with no pregnancy loss. Of the 17 patients with
      quintuplets or more, 10 (59%) delivered live and healthy newborns. No difference
      was found when comparing the transabdominal and the transvaginal approaches.
      CONCLUSIONS: Both transvaginal and transabdominal approaches are comparable.
      There is a remarkable decrease in pregnancy loss with experience.

PMID- 8293846
TI  - Circulating bioactive and immunoreactive recombinant human follicle stimulating
      hormone (Org 32489) after administration to gonadotropin-deficient subjects.
AB  - OBJECTIVE: To study the bioactivity of recombinant and urinary human FSH after
      single IM injection into gonadotropin-deficient subjects. DESIGN: Serum FSH
      levels were measured by immature rat granulosa cell bioassay and immuno
      fluorometric assay. The isohormone distributions of injected FSH materials were
      analyzed by chromatofocusing. Serum samples were collected before, and 6, 24, and
      72 hours after 300 IU of recombinant or urinary FSH. VOLUNTEERS: Fifteen
      gonadotropin-deficient subjects (8 women and 7 men) received recombinant FSH and
      8 of them (4 women and 4 men) received an equal dose of urinary FSH. RESULTS: No
      significant differences were apparent between the bioactive FSH levels after
      recombinant and urinary FSH treatments (n = 8). The immunoreactive FSH levels at
      72 hours after urinary FSH were significantly higher than after recombinant FSH
      injection with values (median and range) of 3.80 (2.76 to 5.75) IU/L (IRP 78/549)
      and 3.10 (1.78 to 4.95) IU/L, respectively. There were no significant changes in
      the bioactive to immunoreactive ratios of FSH within time and between sexes after
      either recombinant FSH (n = 15) or urinary FSH (n = 8). However, the bioactive to
      immunoreactive ratio of the FSH material injected and of the post-treatment serum
      samples were both higher after recombinant FSH than after urinary FSH injection.
      Chromatofocusing revealed that injected recombinant FSH contained more activity
      in the basic fractions than urinary FSH. CONCLUSION: Recombinant human FSH
      maintains its biological activity when injected into gonadotropin-deficient
      subjects. The bioactive to immunoreactive ratio of recombinant FSH was higher
      than that of urinary FSH indicating that recombinant FSH contains relatively more
      basic isohormones, and this finding was strengthened by chromatofocusing.

PMID- 8293847
TI  - Health during prolonged use of levonorgestrel 20 micrograms/d and the copper TCu
      380Ag intrauterine contraceptive devices: a multicenter study. International
      Committee for Contraception Research (ICCR).
AB  - OBJECTIVES: To measure and compare the incidence of adverse events during use of
      two medicated intrauterine devices (IUDs). DESIGN: A multicenter prospective 7
      year randomized study. SETTING: Family planning clinics, primarily in developing
      countries. SUBJECTS: Women age 18 to 38 years at admission, desiring
      contraception and without contraindications to IUDs. MAIN OUTCOME MEASURES:
      Incidence of complaints, conditions, and rates of specific termination for each
      IUD. METHODS: Subjects recorded menstrual events, and clinical staff registered
      all complaints and conditions found on examination at four first-year clinic
      visits and at semiannual visits thereafter. Difference in rates were analyzed by
      chi 2 statistics. RESULTS: Annual pregnancy rates for each IUD averaged 0.2/100
      women whereas upper genital tract infection occurred at rates of 0.6 to 0.7 per
      100 years of use. The levonorgestrel-releasing IUD significantly decreased
      bleeding and spotting days in comparison with historical data for
      noncontraceptors and with the copper-medicated IUD. Dysmenorrhea, vaginitis, and
      myoma in women with the levonorgestrel IUD were markedly decreased in comparison
      with the experience of copper IUD users. Significantly higher rates of
      amenorrhea, delayed ovarian follicular atresia, skin and hair conditions, and
      headache were observed with the steroid IUD than with the copper-releasing IUD.
      Rates of reported adverse effects for either IUD were highest in the first 2
      years of use and among women under age 25. CONCLUSIONS: Long-term use of copper
      or levonorgestrel IUDs is characterized by very low rates of pregnancy and by a
      low and declining annual incidence of side effects, including pelvic infection
      and borderline anemia. The levonorgestrel-releasing IUD reduced the incidence of
      bleeding and, in the long term, of myoma and myoma-related surgery in comparison
      with the copper T IUD. Both IUDs proved highly acceptable and had few
      unanticipated side effects.

PMID- 8293848
TI  - Monocyte-mediated enhancement of endometrial cell proliferation in women with
      endometriosis.
AB  - OBJECTIVE: To investigate the capacity of monocytes from women with endometriosis
      to influence endometrial cell proliferation. DESIGN: Uterine endometrial cells
      were cultured in the presence and absence of autologous blood monocytes for 72
      hours before assessment of endometrial cell proliferation by thymidine
      incorporation. SETTING: Patients were tested at initial presentation for
      evaluation of infertility and/or endometriosis. PATIENTS, PARTICIPANTS: Fertile
      controls, n = 17; infertile controls, n = 9; untreated endometriosis, n = 29.
      INTERVENTIONS: None. RESULTS: Endometrial cell proliferation was enhanced
      significantly by blood monocytes in patients with endometriosis but was
      suppressed significantly by blood monocytes in fertile controls. Endometrial cell
      proliferation was not affected significantly by blood monocytes in infertile
      controls analyzed as a group, but a subset of infertile patients also showed
      enhancement of endometrial cell proliferation by blood monocytes. CONCLUSIONS:
      Blood monocytes from patients with endometriosis and a subset of patients with
      unexplained infertility enhance autologous endometrial cell proliferation,
      whereas blood monocytes from fertile patients suppress endometrial cell
      proliferation. The capacity of monocytes to enhance endometrial cell
      proliferation appears to require both monocyte-derived factors that stimulate
      endometrial cell proliferation and endometrial cells capable of responding to
      those stimulatory factors. If either of these factors is absent, monocytes either
      suppress or have no effect on endometrial cell proliferation.

PMID- 8293849
TI  - Expression of integrins and E-cadherin in cells from menstrual effluent,
      endometrium, peritoneal fluid, peritoneum, and endometriosis.
AB  - OBJECTIVE: To detect the expression of integrins and E-cadherin in cells from
      peritoneal fluid (PF), endometrium, menstrual effluent, peritoneum, and
      endometriotic lesions during the early follicular phase of the menstrual cycle.
      DESIGN: An immunohistochemical study. SETTING: Tertiary care university medical
      center. PATIENTS: Sixteen patients undergoing a diagnostic laparoscopy as part of
      a subfertility work-up. All patients had regular and ovulatory cycles.
      INTERVENTIONS: A laparoscopy was performed in the early follicular phase (days 2
      to 5). Simultaneously, samples were taken from endometrium, menstrual effluent,
      and PF, and a representative biopsy of an endometriotic lesion was obtained. If
      endometriosis was not noted, a peritoneal biopsy was obtained instead. MAIN
      OUTCOME MEASURES: The expression of cell adhesion molecules, including the
      integrin alpha 2 beta 1, alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1, and
      alpha 6 beta 1 and E-cadherin, as determined by immunohistochemistry on frozen
      sections. RESULTS: All integrins tested could be detected in the endometrium
      samples and in endometriotic lesions. In menstrual effluent samples, positive
      staining for the integrins alpha 2 beta 1 and alpha 3 beta 1 was found in
      epithelial cells in 13 of 16 cases. Integrin alpha 5 beta 1 was detected in 11 of
      16 samples, and integrins alpha 4 beta 1 and alpha 6 beta 1 were detected in 5 of
      16 samples. In PF, integrin alpha 3 beta 1 was found in epithelial cells in 12 of
      16 samples, integrin alpha 5 beta 1 in 5 of 16, and integrins alpha 4 beta 1 in 2
      of 16. The antibody for E-cadherin showed positive staining of epithelial cells
      in 6 of 16 menstrual effluent samples. All endometrial tissue samples showed
      positive staining for E-cadherin. In PF, E-cadherin was detected in the
      epithelial cells of one sample. One peritoneum biopsy revealed positive staining
      for E-cadherin. CONCLUSION: Integrins alpha 2 beta 1, alpha 3 beta 1, alpha 4
      beta 1, alpha 5 beta 1, and E-cadherin, important cell adhesion molecules, are
      expressed in endometriotic lesions and in cells and tissues that are potentially
      involved in the development of endometriosis. These cell adhesion molecules could
      be involved in the shedding of endometrial tissue during menstruation and the
      attachment of endometrial tissue fragments to the peritoneum.

PMID- 8293850
TI  - Growth factor effects on endometrial epithelial cell differentiation and protein
      synthesis in vitro.
AB  - OBJECTIVE: To develop a baseline for projected studies of a rat endometriosis
      model. DESIGN: We investigated the effects of two macrophage-related growth
      factors, platelet-derived growth factor (PDGF) and transforming growth factor
      beta (TGF-beta), on proliferation, in vitro differentiation, and protein
      secretion of uterine epithelial cells from immature rats. Uterine epithelial
      cells grown on matrix covered filters were treated with growth factors (GFs) or
      estrogen and/or P. Incorporation of [35S]methionine by polarized uterine
      epithelial cell proteins and secretion of labeled proteins into apical and basal
      culture medium were examined. SETTING: Department of Cell Biology, Baylor College
      of Medicine, Houston, Texas. MAIN OUTCOME MEASURES: Cell associated and secreted
      proteins were resolved by gel electrophoresis, fluorography, and immunoblotting.
      Proliferation was quantified by cell counts in parallel cultures by
      hemocytometer. RESULTS: Estrogen and P increase protein synthesis by uterine
      epithelium. Transforming growth factor-beta depressed protein synthesis and
      secretion in uterine epithelial cells. Platelet-derived growth factor appears to
      have no effect on epithelial protein synthesis or secretion and does not modulate
      the effect of TGF-beta. Estrogen and P increase complement component 3 (C3)
      production by epithelial cells. CONCLUSION: Macrophage-secreted GFs may play a
      role in the development and maintenance of ectopic endometrial tissue. Both TGF
      beta and ovarian steroids may participate in the dynamic regulation of protein
      synthesis by ectopic uterine epithelium. These molecules may indirectly affect
      the macrophage-stromal axis through nonspecific modulation of C3 secretion.
      Platelet-derived growth factor appears to have no direct effect on uterine
      epithelial cells. The recognized effect of PDGF on ectopic endometrial tissue is
      most likely mediated via the stromal component.

PMID- 8293851
TI  - Age-related decline in female fertility is not due to diminished capacity of the
      uterus to sustain embryo implantation.
AB  - OBJECTIVE: To evaluate the contribution of the uterus to age-related reproductive
      failure in women. PATIENTS: Thirty-eight ovum donors (30.2 +/- 4.9 years [mean +/
      SD]) donating oocytes throughout 102 ovum donations. Fifty-one cycles were
      documented in "younger" recipients (35.8 +/- 3.1 years) and 51 in "older"
      recipients (44.0 +/- 3.1 years). The study was prospectively designed; same
      cohort oocytes obtained from one young donor during a specific cycle were evenly
      distributed between "young" and "old" ovum recipients. Use of oocytes from a
      single source and a unique ovulatory cohort provides strict control over oocyte
      quality. Uterine age is varied by design, according to the age of the recipient
      at the time of ET. The role of the aging uterus in the decline of female
      fertility can be thus isolated and scrutinized. RESULTS: No significant (NS)
      difference in the number of ova received (7.9 +/- 3.4 versus 7.0 +/- 3.5), ova
      fertilized (4.4 +/- 1.5 versus 4.5 +/- 2.3), or embryos transferred (4.1 +/- 1.5
      versus 4.1 +/- 1.6) was observed between the < 40 and > or = 40 recipient age
      groups. A total of 23 pregnancies occurred among the 102 ETs (22.6%). Eleven
      clinical pregnancies (21.6%) resulting in 10 deliveries were observed in the < 40
      recipient age group, and 12 clinical pregnancies (23.5%) leading to 10 deliveries
      occurred in the > or = 40 recipient age group (NS). The pregnancy loss rates were
      9.1% (1 of 11) and 16.7% (2 of 12) for the two recipient age groups,
      respectively, (NS). CONCLUSION: The capacity to conceive and to gestate a
      conception to term when oocyte quality is controlled appears to be independent of
      uterine aging through the fifth decade of life.

PMID- 8293852
TI  - [Production of mineralocorticoid and enzyme expression for steroidogenesis in
      blood vessels as components of the vascular auto-/paracrine system].
AB  - With the recent advance in immunohistochemical and molecular-genetic techniques,
      all of the components of the renin-angiotensin system (RAS) have been shown to
      exist in the vascular tissue of various animal species as well as in humans. The
      author's group previously reported that angiotensin II (AII) was generated in the
      mesenteric arteries of several experimental rat models. Vascular AII generation
      appears to be regulated independently of circulating renin levels, as suggested
      by the expression of tissue-specific angiotensinogen mRNA. In the light of recent
      reports that aldosterone may be synthesized in the cultured endothelial cells
      from bovine aorta, and that 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD)
      plays a key role in determining the specificity in mineralocorticoid activity in
      various mineralocorticoid-responsive tissues, the author wishes to review the
      studies carried out by colleagues on the production of aldosterone with its
      precursor steroids and enzyme expression for aldosterone synthesis in the blood
      vessels as the components of the vascular auto-/paracrine system. The first part
      of the present paper is summarized as follows: 1) With Northern blotting and RT
      PCR of the RNA which was prepared from rat arterial tissue or cultured human
      arterial smooth muscle cells (SMC), the expression of mineralo- and
      glucocorticoid receptors was confirmed. 2) The vascular production of aldosterone
      and corticosterone from the rat mesenteric artery was demonstrated in analyzing
      the arterial perfusates using a HPLC and GC/MS. Moreover, in this ex vivo
      experiment, the production of aldosterone in the vasculature was found to be
      partially controlled by angiotensin II generated locally. 3) It was clearly
      demonstrated using an RT-PCR method for the first time that aldosterone synthase,
      cytochrome P450aldo (c 18 or c mo); CYP 11B2 messenger RNA is expressed in the
      cultured endothelial cells (EC) from human pulmonary artery. From these data, the
      author would like to propose the concept of a vascular renin-angiotensin
      aldosterone system under which paracrinaly produced mineralocorticoid in the
      vascular EC may easily reach the vascular SMC and in turn act to increase the
      vascular tone through binding to the receptor there. The second part can be
      summarized as follows: 1) The expression of 11 beta-HSD in the vasculature was
      confirmed by bioassay using ex vivo experiment of the isolated rat mesenteric
      artery perfusion system, immunocytochemical staining methods, in situ
      hybridization and also by Northern blot analysis.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8293853
TI  - [Clinical application of recombinant thyroid peroxidase].
AB  - TPO is a major antigen corresponding to thyroid-microsomal autoantibodies. Anti
      TPO autoantibodies are very important to diagnose autoimmune thyroid disease and
      to estimate its clinical course. An EIA for measuring anti-TPO autoantibodies
      (rhTPO-EIA) was developed using recombinant human TPO expressed in CHO cells and
      was compared with MCHA generally used in routine laboratory work. Sera from
      patients with various disorders were measured for their anti-TPO autoantibodies.
      Chronic thyroiditis and Graves' disease were highly positive, while thyroid
      cancer, adenoma, SLE, and RA were low in their positivity. The positive rate of
      anti-TPO autoantibodies were compatible with those of previous reports of each
      disorder. In the comparison between rhTPO-EIA and MCHA, the correlation
      coefficient was 0.486. Following absorption with thyroglobulin, sera were
      measured again and as a result, the correlation coefficient increased to 0.723.
      Therefore, MCHA was thought to be influenced in the presence of anti
      thyroglobulin autoantibodies. The characteristics of TPO antigen and anti-TPO
      autoantibodies were also summarized.

PMID- 8293854
TI  - [The effects of short and long duration of hypothyroidism on prolactin secretion
      in rats].
AB  - The aim of the present study was to evaluate the time-dependent effect of an
      experimentally induced hypothyroid state on prolactin (PRL) secretion in rats.
      Treatment with radioactive iodine and propylthiouracil (PTU) resulted in reduced
      serum concentrations of total thyroxine and triiodothyronine, and increased serum
      TSH concentrations in rats one week after the start of the treatment. Basal serum
      PRL concentrations were not significantly altered in 1-, 2- and 4-week
      hypothyroid rats, whereas in 8-week hypothyroid rats, serum PRL concentrations
      were significantly reduced and remained depressed throughout 24 weeks of PTU
      ingestion. The PRL response to i.p. administration of haloperidol (0.5mg/kg) was
      significantly reduced after one week of PTU ingestion. When the duration of
      hypothyroidism was increased, there was a progressive fall in the PRL response to
      haloperidol that reached the lowest value after 12 weeks of PTU ingestion. The
      PRL response to an i.v. bolus injection of vasoactive intestinal peptide (VIP,
      150 mu g/kg) was markedly reduced in hypothyroid rats after one week of PTU
      ingestion and reached the lowest value after two weeks. The PRL response to VIP
      was progressively recovered after treatment for 4 weeks with PTU, and reached the
      highest value in 24-week hypothyroid rats. However, the PRL response to VIP in 24
      week hypothyroid rats was significantly lower than that in euthyroid rats. Serum
      PRL response to an i.v. bolus injection of beta -endorphin (450 mu g/kg) was
      significantly reduced in 8-week hypothyroid rats. Dopamine (DA) concentrations in
      the pituitary and the hypothalamus were not significantly altered in 2-week
      hypothyroid rats. In contrast, DA concentrations were significantly increased in
      both the pituitary and hypothalamus in 8- and 24-week hypothyroid rats. These
      findings observed in hypothyroid rats were reversed by the administration of
      thyroxine and triiodothyronine for 9 days. The present results support a
      modulatory role for thyroid status in regulating the concentration of DA in the
      pituitary and the hypothalamus, and consequently on PRL secretion by the
      pituitary. This suggests that PRL releasing factors do not appear to play a major
      role in PRL secretion in hypothyroid rats. These data also indicate that
      alterations in PRL secretion and DA concentrations in the pituitary and the
      hypothalamus in the hypothyroid state become more prominent as the duration of
      hypothyroidism increases.

PMID- 8293855
TI  - [Unidentified steroid hormone of Cushing's syndrome and disease].
AB  - A previously unknown HPLC peak was recently observed in urine samples from
      patients with Cushing's syndrome and disease. We analysed dansylated derivatives
      of 17keto steroid glucuronides in urine samples from patients with Cushing's
      syndrome, Cushing disease and from healthy subjects using high-performance liquid
      chromatography (HPLC) on reversed-phase Cap Cell PakC8. All urine samples from
      patients with Cushing's syndrome caused by adrenal adenoma and Cushing's disease
      showed an unknown large peak at the point between [110HE-G] and [110HA-G] peaks
      and at a retention time of 25.4 min. The same unknown peak was also observed in
      urine samples from a patient with asymptomatic cortisol-producing adrenal adenoma
      and two patients with ectopic ACTH-producing tumor, though the peak height was
      low for the former and one of the latter but high for the second of the two
      patients. In contrast, healthy male and female urine only showed a very small
      peak at the same retention time. Urine samples from a Cushing disease treated
      with op'DDD and Cushing's syndrome bilaterally adrenalectomized and treating with
      cortisol showed no such peak. The retention time of this unknown peak is clearly
      different from that of seven 17keto steroid standard glucuronide conjugates. The
      structure of this substance may be closely related to [110HE-G] or [110HA-G].

PMID- 8293856
TI  - [Statistic analysis for the association of hormone dynamics and biochemical
      parameters with bone turnover in surgically induced menopause].
AB  - The association between hormone dynamics and bone turnover was statistically
      examined in 52 women with surgically induced menopause. The mean values of 19
      laboratory items which included hormones as well as parameters of bone metabolism
      were obtained and analyzed by Spearman's rank test. Linear regression models were
      established. Based on Pearson's correlation matrices, the principal components
      were analyzed. Matrices were formed from factor loading derived from Varimax's
      rotation, and their statistical significance was evaluated. 1. Significant
      correlations were determined from both the examination of the data analyzed
      separately at the levels of artificial menopause (bilateral and unilateral) and
      oophorectomy (OVX) method (bilateral or unilateral). For the patients who had
      bilateral OVX, the pairs showing a positive correlation (0.01 < P, 0.05 < P) were
      1-25-(OH)2D with E2 or ASD, 25-(OH)D with E2, E3, Progesterone, or ASD, CT with
      Progesterone, ASD, or Testosterone, S.A1-P with FSH or LH, and S.Ca with LH. The
      pairs showing a weaker positive correlation were PTH with E2 or E3, CT with E2,
      E3 with S.Acid-P or U.Ca/CRN, and S.Ca with FSH. The pairs showing a negative
      correlation (0.01 < P, 0.05 < P) were S.A1-P with E2 or Progesterone, and S.Ca
      with Testosterone. The pairs showing a weaker negative correlation were S.A1-P
      with ASD. For the patients who had unilateral OVX, the pairs showing a positive
      correlation were 1-25-(OH)2D with E2, ASD, or Testosterone, 25-(OH)D with E2, E3,
      Progesterone, or ASD, CT with Progesterone, ASD, or Testosterone, and PTH with
      ASD. The pairs showing a weaker positive correlation were PTH with E2 or E3, and
      CT with E2. The pairs showing a negative correlation were S.Ca with Testosterone.
      The pairs showing a weaker negative correlation were S.A1-P with ASD. There was a
      small but significant difference between the two groups. However, Estrogen and
      Androgen in sex steroids, and S.A1-P, S.Ca, CT, PTH, 1-25-(OH)2D, and 25-(OH)D in
      bone parameters, all changed early or late at different rates but participated
      concomitantly with the high bone turn-over induced by OVX, particularly in
      bilateral. 2. Significant correlations among all parameters were determined for
      data analyzed at the level of artificial menopause.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8293857
TI  - [After the announcement of the results of DCCT (Diabetes Control and
      Complications Trial)].

PMID- 8293858
TI  - Hypoglycaemia in insulin-dependent diabetes mellitus: facts for the 1990s.

PMID- 8293859
TI  - D-glucose metabolism in tumoral pancreatic islet cells with rapid or decreased
      mitotic activity.
AB  - The metabolism of D-glucose was investigated in tumoral islet cells of the RINm5F
      line with either unaltered or decreased mitotic activity, resulting from the
      incorporation of D, L-alpha-difluoromethylornithine (DFMO) in the culture medium.
      In DFMO-treated cells, the oxidation of D-[3,4-14C]glucose was less severely
      affected than the utilization of D-[5-3H] glucose, at least at hexose
      concentrations in the 1.0 to 16.7 mM range. This coincided with restoration of
      the process of glucose-induced stimulation of 3HOH generation from [2
      3H]glycerol. Pretreatment with DFMO also resulted in a decreased circulation in
      the pentose phosphate pathway and the restoration of a preferential stimulation
      of D-[2-14C]glucose or D-[6-14C]glucose oxidation relative to D-[5-3H]glucose
      utilization when raising the hexose concentration from 0.2 to 1.0 mM. It is
      proposed that the interference of cell growth with the metabolic and functional
      responses of RINm5F cells to D-glucose is relevant to the difference between such
      responses otherwise found when comparing the behaviour of foetal or neonatal to
      adult normal islets.

PMID- 8293860
TI  - Plasma lactate concentration in obesity and type 2 diabetes.
AB  - The purpose of this study was three-fold: 1) to define the effects of obesity and
      Type 2 diabetes on plasma lactate concentrations; 2) to relate changes in plasma
      lactate concentration to plasma glucose and insulin concentrations; and 3) to
      evaluate the effect of differences in blood sample processing on plasma lactate
      determination in a disparate population group. To accomplish this, fasting plasma
      lactate concentrations were determined in 30 volunteers (10 non-obese individuals
      with normal glucose tolerance, 10 obese individuals with Type 2 diabetes) on
      blood drawn, processed, and maintained in a variety of ways. Results demonstrated
      that fasting plasma lactate measurements were least confounded when blood was
      drawn without the subject "hand pumping" following venous occlusion, the samples
      maintained on ice at 4 degrees C until precipitated with perchloric acid, and
      kept as this temperature until lactate concentration was determined. Under these
      conditions, plasma lactate concentration was lowest in the non-obese group with
      normal glucose tolerance (0.81 +/- 0.07 mmol/L), highest in the obese subjects
      with Type 2 diabetes (1.46 +/- 0.14 mmol/L), and intermediate in obese
      individuals with normal glucose tolerance (1.17 +/- 0.13 mmol/L). All three
      groups were significantly different from each other. In addition plasma lactate
      concentrations were associated with both fasting plasma glucose and glycated
      haemoglobin concentrations.

PMID- 8293861
TI  - Serum LpAI lipoprotein particles in diabetic patients with and without renal
      lesions of different grades.
AB  - Among high density lipoprotein particles, LpAI particles which contain
      apolipoprotein A1 alone, appear to be involved in cholesterol transport from
      peripheral tissues to the liver. The aim of this cross-sectional study was to
      examine serum LpAI particle concentrations in Type 1 and Type 2 diabetic patients
      with renal lesions of differing grades, in comparison with normal controls and
      with nondiabetic patients presenting with chronic renal failure. LpAI
      concentrations and LpAI-to-apo A1 ratios were increased in Type 1 diabetic
      patients with normal albumin excretion. In Type 1 and in Type 2 diabetic patients
      with increased urinary albumin excretion, LpAI concentrations and LpAI-to-apo A1
      ratios were found to be not different from those of normal controls. In diabetic
      and in nondiabetic patients with chronic renal failure, LpAI concentrations were
      decreased. These abnormalities may contribute to the development of macrovascular
      complications.

PMID- 8293862
TI  - Incidence of childhood diabetes did not increase in Estonia during 1980-89.
AB  - The purpose of the study was to evaluate the temporal variation in the incidence
      of Type 1 diabetes in Estonia for 1980-89. Data were taken from the Estonian
      Childhood Type 1 Diabetes Register. "Poisson" regression modelling was completed
      with GLIM software adjusting for age and ethnic groups. No calendar period effect
      was found, either when allowing for distinct period effects, or looking for
      trends. No urban-rural difference was detected in the incidence of childhood
      onset Type 1 diabetes. In conclusion, our analysis provides evidence that the
      incidence of childhood Type 1 diabetes was relatively stable in Estonia during
      the past decade in contrast to some other Baltic countries where a significant
      increase has been reported.

PMID- 8293863
TI  - Experience with intraperitoneal insulin infusion from implantable programmable
      systems in type 1 (insulin-dependent) diabetes mellitus previously treated by
      external pumps.
AB  - The feasibility of the continuous intraperitoneal insulin infusion from
      implantable programmable systems was evaluated in 17 Type 1 (insulin-dependent)
      diabetic patients currently treated by external pumps. Eight subjects were using
      a continuous subcutaneous insulin infusion (cumulated experience: 7.4 patients x
      years) and nine subjects had a cumulated experience of 61.4 patients x years of
      continuous intra peritoneal insulin delivery by external pumps. The two studied
      implantable systems (A and B) were delivering the same pH neutral surfactant
      stabilized semi-synthetic human insulin, but at the respective concentrations of
      400 units per ml in group A (n = 12) and of 100 units per ml in group B (n = 5),
      via a peritoneal catheter. The pump was implanted in a subcutaneous pocket
      created in the abdominal wall under general anesthesia. The reported trial of
      implantable programmable systems is 21 patient x years with an individual
      experience of 1.2 +/- 0.4 years (mean +/- SD). A sustained and stable glycaemic
      control was obtained, as indicated by the haemoglobin A1c: 7.4 +/- 1.3% (normal
      range: 4.3-6.1%), the mean blood glucose: 7.4 +/- 2.1 mM.l-1, the standard
      deviation of blood glucose values: 3.4 +/- 0.4 mM.l-1 and the percentages of 13.1
      +/- 4.5% and 6.1 +/- 6.1% of blood glucose values respectively over 11 mM.l-1 and
      under 2.8 mM.l-1 after one year. The only metabolic event to occur was one
      episode of ketoacidosis secondary to a catheter obstruction. No hypoglycaemic
      coma occurred contrasting with incidences of 0.54 and 0.05 per patient x year
      during subcutaneous external and intraperitoneal pumps respectively (p <
      0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293865
TI  - [Hormone replacement therapy of menopause in women with vascular risk factors].

PMID- 8293864
TI  - Predictive value of age-related acute insulin response to glucose in subjects at
      risk for type 1 diabetes: results of a 6-year follow-up study from west-France.
AB  - The acute insulin response to i.v. glucose (AIRG) was evaluated in 344 first
      degree relatives of patients with Type 1 diabetes. In 318 relatives aged 3 to 48
      years without islet cell antibody and insulin autoantibody, correlations (p <
      0.0006) were found between age and fasting insulinaemia, fasting glycaemia, or
      AIRG, with a peak during puberty. Assuming that these relatives without islet
      cells and insulin auto-antibodies have a low risk of developing Type 1 diabetes,
      we provided a "standard age-related chart" for AIRG with a "low" AIRG defined as
      a value below the 1st percentile for each pubertal stage. Using these cut-off
      points, predictive characteristics of a low AIRG for progression towards diabetes
      within 6 years were analysed. Four relatives developed diabetes and one displayed
      impaired oral glucose tolerance. Four out of these 5 subjects had islet cell and
      insulin auto-antibodies, but the other one was negative for these markers. Three
      of these 5 subjects had low AIRG at entry (30, 24 and 1 months before diabetes,
      respectively). The two others displayed a steady progressive decline (p < 0.02)
      of age-related during the follow-up before impaired oral glucose tolerance and
      diabetes appeared (rate of decline: 15 microU/ml/year). Thus, independently of
      the presence of islet cell antibodies, the predictive value of a low age-related
      AIRG during the follow-up is greater than the single low AIRG at entry.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8293866
TI  - Formation of the adult rudiment of sea urchins is influenced by thyroid hormones.
AB  - After the sea urchin embryo has developed to a pluteus larva, the adult rudiment
      (sea urchin rudiment) is formed, with other adult structures, on the left side of
      the larva and finally the juvenile sea urchin is formed after metamorphosis. We
      report here that thyroid hormones (THs) are involved in the formation of the
      adult rudiment and the adult-type skeleton and the resorption of larval tissues
      of the sea urchin. The contents of THs in the larval body were determined by
      radioimmunoassay after the separation of individual THs by HPLC. We confirmed the
      presence of THs in the larval body and in algae on which the larvae feed. The THs
      accumulate gradually following the development of the larva and reach maximum
      levels at the eight-armed stage when the adult rudiment is completed. These
      results suggest that the development of the larva is influenced by THs
      accumulated in the larval body. However, inhibitors for the synthesis of THs do
      not affect the development of the larval body, suggesting a supply of THs from
      algae.

PMID- 8293867
TI  - The expression of B-cadherin during embryonic chick development.
AB  - Cadherins compose a family of calcium-dependent cell adhesion molecules that are
      involved in the segregation of differentiating tissues during development. Each
      cadherin has a unique spatial and temporal pattern of expression. As has been
      observed for other cadherins, B-cadherin, when expressed in mouse L929
      fibroblasts, confers upon them a calcium-dependent cell aggregation activity. A
      monoclonal antibody to B-cadherin was isolated and used to determine the pattern
      of expression of B-cadherin in the developing chick embryo. Antibody staining and
      in situ hybridization reveal that B-cadherin protein and mRNA are found in
      diverse epithelia derived from each of the three primary germ layers, where their
      expression is strikingly regulated during differentiation. In some instances, the
      regional distribution of B-cadherin within a tissue reflects the distinct
      functional regions of the tissue. Patterns of staining are similar to, but
      distinct from, those seen with anti-LCAM antibodies. Although there are many
      examples where B-cadherin and LCAM are coexpressed, there are also distinctive
      regional differences.

PMID- 8293868
TI  - Expression of the connexin43 gap junctional protein in tissues at the tip of the
      chick limb bud is related to the epithelial-mesenchymal interactions that mediate
      morphogenesis.
AB  - The pattern of connexin43 expression in developing chick limb buds was examined
      using a site-specific polyclonal antibody and confocal microscopy. Connexin43 is
      expressed at stages of limb development when epithelial-mesenchymal interactions
      are occurring that mediate morphogenesis. Extensive labeling was observed in the
      apical ectodermal ridge and labeling was also found in underlying mesenchyme
      cells at the tip of the bud. In mouse limb buds, the same gap junction protein is
      expressed only in the apical ridge. Manipulations of developing chick wing buds
      show that mesenchymal expression of connexin43 appears to be controlled by the
      apical ectodermal ridge. When the apical ridge is surgically removed and limb
      truncations result, mesenchymal labeling is markedly reduced and conversely the
      grafting of an additional ridge induces connexin43 expression between underlying
      mesenchymal cells which do not normally show expression at this stage of
      development. In addition, a treatment with retinoic acid that flattens the apical
      ridge and inhibits bud outgrowth reduces expression in both mesenchymal and
      epithelial tissues. The abolition of connexin43 expression in mesenchymal and
      epithelial domains when bud outgrowth is halted suggests that synthesis of this
      gap junction protein is related to the epithelial-mesenchymal interactions that
      mediate morphogenesis of the bud.

PMID- 8293869
TI  - A complete culture system for avian transgenesis, supporting quail embryos from
      the single-cell stage to hatching.
AB  - We report here a method to produce quail hatchlings by culture in vitro from the
      single-cell stage. The culture is composed of three steps. In the first step, the
      fertilized ovum surrounded by thick albumen obtained from the magnum is cultured
      for 24 hr at 41.5 degrees C in a tightly sealed 20-ml plastic cup with chicken
      thin albumen added to the equator level of the ovum (System Q1). In the second
      step, a quail egg shell, cut horizontally and emptied, is used as a bed shell.
      After the thick albumen is removed, the embryo with egg yolk is transferred to
      the bed shell and thin albumen from chicken eggs is added to fill the shell.
      Then, the embryo is cultured for an additional 52 hr at 37.5 degrees C while
      being rocked at an angle of 90 degrees at 30-min intervals (System Q2). The
      embryo is transferred again to a chicken bed shell and cultured at 37.5 degrees C
      with rocking at a 30-degree angle (System Q3). Just before hatching, the rocking
      of embryos is stopped. The procedure yielded a hatchability of 25%. For
      transgenesis, a plasmid construct containing a beta-actin-lacZ hybrid gene
      (pMiwZ) is microinjected into the ovum at the single-cell stage, which is
      cultured in vitro for 85-90 hr using Systems Q1 and Q2 consecutively. Seven out
      of 17 surviving embryos exhibited lacZ gene expression in embryonic tissues as
      detected by histochemistry. The procedure described here should be highly
      applicable for the production of transgenic birds.

PMID- 8293870
TI  - Development of FGF-dependency in human embryonic carcinoma cells after retinoic
      acid-induced differentiation.
AB  - Rapidly growing human teratocarcinoma cells (Tera-2) can be induced to
      differentiate into quiescent, nontumorigenic cells expressing neuronal markers.
      To more closely mimic the in vivo conditions for tumor growth, we grew Tera-2
      cells in three-dimensional collagen gel cultures. The undifferentiated cells
      proliferated in the gel, forming tight colonies. Addition of soluble fibroblast
      growth factor 1 or 2 (FGF1 or FGF2) into the gel resulted in scattering of single
      cells throughout the collagen gel. In a FGF gradient the cells moved rapidly
      toward a higher concentration. On the contrary, cells first differentiated for 8
      days in retinoic acid died within a few days after transfer into the collagen
      gel. Alternatively, if retinoic acid was included in the collagen gel, the
      proliferating undifferentiated cells died after 4-5 days in the gel. This
      differentiation-related cell death was completely opposed by including FGF in the
      collagen gel. When placed in the FGF gradient, the fully differentiated cells
      survived at the areas of higher FGF concentration, but no more migrated. The
      survival of retinoic acid-differentiated Tera-2 cells in collagen was also
      mediated by direct contact with glioma cells or the heparan sulfate-rich portion
      of glioma or endothelial cell matrix. These effects on differentiated cells were
      sensitive to inhibition by affinity-purified anti-FGF2 IgG. Thus, FGF has the
      potential to act as a migration-inducing factor either in solution or, more
      likely, in vivo, as an immobilized, matrix-bound growth factor directing the
      movement of responsive cells. The development of differentiation-associated FGF
      dependency allows survival of the cells only at places where they are in close
      contact with either FGF-synthesizing cells or FGF-rich extracellular structures
      such as basement membranes.

PMID- 8293871
TI  - The osmolarity of adult Drosophila hemolymph and its effect on oocyte-nurse cell
      electrical polarity.
AB  - In ovarian follicles of Drosophila, changes in external osmolarity affect the
      steady-state potentials of oocytes more than those of nurse cells. Thus the
      osmolarity of the incubation medium affects the occurrence and the direction of
      an electrical gradient across the connecting intercellular bridges. At 255 mOsm
      nurse cell Em averaged 2.5 mV negative to oocyte Em (P < 0.001). At 275 and at
      300 mOsm there was no significant difference between oocyte and nurse cell. At
      400 mOsm nurse cell Em averaged 1.1 mV positive to oocyte Em (P = 0.007). The
      osmolarity of adult Drosophila hemolymph was measured by a variation of freezing
      point depression and averaged 251 +/- 9 (SE) mOsm. The measured osmolarity and
      measured ionic concentrations of adult Drosophila hemolymph were used to develop
      an incubation medium, which was used to incubate developing ovarian follicles.
      Electrical measurements made in this saline, which mimics in vivo conditions,
      confirmed reports of a nurse cell-oocyte electrical gradient, with nurse cell Em
      significantly more negative than oocyte Em. Microinjections of the negatively
      charged dye Lucifer yellow CH showed that this charged molecule accumulated in
      the oocyte at the in vivo osmolarity, and in the nurse cells at highly elevated
      osmotic levels.

PMID- 8293872
TI  - Immunohistochemical analysis of the Brachyury protein in wild-type and mutant
      mouse embryos.
AB  - The murine Brachyury (T) gene is required in posterior mesoderm formation and
      axial development. Mutant embryos lacking T gene function are deficient in
      notochord differentiation and posterior mesoderm formation, but make anterior
      mesoderm. Posterior axial development requires increasing T activity along the
      rostrocaudal axis. The T gene is transiently transcribed in nascent and migrating
      mesoderm and continuously in the notochord. The maintenance of T expression in
      the notochord depends, directly or indirectly, on wild-type T activity. In
      Xenopus it has been shown that the onset of T expression occurs in response to
      mesoderm-inducing growth factors. The T protein is binding to DNA and is probably
      involved in the control of gene expression. Here we show that the T protein is
      located in the nucleus. We have analyzed the expression pattern of T protein in
      wild-type and mutant embryos from early primitive streak formation to the end of
      the tail bud stage. Throughout all stages of mesoderm formation T protein is
      transiently present in nascent and migrating mesoderm. In the notochord T protein
      persists to the end of the tail bud stage. It is also transiently detectable in
      the forming gut endoderm and in prospective neuroectoderm of later embryos. This
      shows that T expression is not strictly correlated with a commitment of cells to
      mesoderm. The analysis of the tail development of TWis/+ mutant embryos
      demonstrated that the formation of the neural tube, gut, and somites from the
      tail bud proceeds in the absence of a notochord. The maintenance and
      differentiation of these structures, however, seems to depend on signals from the
      notochord.

PMID- 8293873
TI  - Nerve growth factor derived from terminals selectively increases the ratio of p75
      to trkA NGF receptors on mature sympathetic neurons.
AB  - Exposure of neuronal terminals to target-derived NGF has been hypothesized to
      regulate cell body responses at a distance. To test this hypothesis and, more
      specifically, to determine whether NGF distally regulates the synthesis of its
      two characterized receptors, we developed the following paradigm. Sympathetic
      neurons of the superior cervical ganglion (SCG) that project either to the eye or
      to the ear were labeled, in adult animals, with the retrograde tracers Fast Blue
      and Fluoro-Gold, respectively. NGF was then injected daily into the anterior
      chamber of one eye, exposing the terminals of the ipsilateral eye neurons to
      increased NGF. To control for systemic and/or localized injury effects,
      cytochrome C or PBS were injected into the contralateral eye of the same animals.
      In situ hybridization and image analysis were then used to determine neuronal
      levels of p75 NGF receptor, trkA, and T alpha 1 alpha-tubulin mRNAs, with the
      latter providing a correlative measure of neuronal sprouting. Morphological
      measurements revealed that exogenous, terminally-derived NGF increased the mean
      cross-sectional area of eye neurons by 37%. Grain counts for p75 NGF receptor
      mRNA increased from 2- to 6-fold in the NGF-treated neurons, and grain densities,
      which accounted for neuronal hypertrophy, also increased significantly. In
      contrast, grain counts for trkA mRNA were not significantly increased by this
      treatment, while T alpha 1 alpha-tubulin mRNA levels increased only 1.5- to 2
      fold. No increase in grain density was detected for either of these mRNAs. The
      NGF-induced increased in p75 NGF receptor mRNA levels was accompanied by terminal
      sprouting and by an increase in the density of p75 NGF receptors on terminal
      neurites, as indicated by IgG-192 immunostaining of the NGF-treated iris. These
      data therefore suggest that, in addition to promoting local sprouting, increased
      target-derived NGF increases the levels of p75 NGF receptor relative to trkA on
      terminal neurites, by differentially regulating receptor synthesis. Such a direct
      regulatory feedback loop may well play an integral role in precisely modulating
      neuronal responses as a function of the amount of available trophic support
      and/or target tissue.

PMID- 8293874
TI  - Induction of rapid osteoblast differentiation in rat bone marrow stromal cell
      cultures by dexamethasone and BMP-2.
AB  - Adult vertebrates require a continuous supply of osteoblasts for both bone
      remodeling and regeneration during fracture repair. This implies the existence of
      a reservoir of cells in the body capable of osteogenesis. One source of these
      osteoprogenitors is the stem cells within the fibroblastic component of bone
      marrow stroma. Mature osteoblasts are characterized by high alkaline phosphatase
      and osteopontin levels, combined with expression of the bone-specific matrix
      proteins osteocalcin and bone sialoprotein and the capacity for matrix
      mineralization. We have used these markers to define the conditions permitting
      rapid osteoblast differentiation from cultured bone marrow stromal cells.
      Osteoblastic differentiation was induced by continuous culture with 10(-8) M
      dexamethasone (dex) which stimulated alkaline phosphatase (AP) activity and mRNA
      levels as well as osteopontin, bone sialoprotein, and osteocalcin mRNA by Day 8
      of culture; coaddition of 10(-8) M 1,25-dihydroxyvitamin D3 (vitamin D) with dex
      was essential for high osteocalcin mRNA expression. Recombinant bone
      morphogenetic protein-2 (BMP-2) exerted similar effects to dex and acted in
      synergy with dex to yield greatly elevated AP activity as well as increased
      levels of osteoblastic mRNAs. Using in situ hybridization to detect the presence
      of mRNAs in individual cells, it was shown that appearance of osteopontin mRNA
      preceded AP mRNA, and was expressed in dex-treated cell colonies as early as Day
      4. Quantitation of cell surface AP protein by flow cytometry indicated that
      culture with dex or BMP-2 produced a mixed population of cells with low AP (dim
      cells) and cells with high AP levels, while the combination of dex + BMP-2
      yielded very few dim cells and a population of cells containing higher AP levels
      than with either inducer alone. When the dim population from dex-treated cells
      was sorted and recultured with inducers, these cultures developed high AP levels
      and were able to deposit a mineralized matrix. Thus, treatment of marrow stromal
      cells with inducer results in a population of mature osteoblasts as well as a
      population of undifferentiated cells which retains the capacity for osteoblastic
      differentiation with further exposure to inducers. These data demonstrate that
      stem cells within the stromal compartment of bone marrow are capable of rapidly
      acquiring osteoblast features and suggest a potential role for glucocorticoids in
      combination with BMP-2 and vitamin D in stages of osteogenic development.

PMID- 8293875
TI  - Developmentally regulated alternative splicing of a nematode type IV collagen
      gene.
AB  - A comparison of the genomic DNA sequence that encodes the Ascaris suum alpha
      2(IV) collagen chain with the corresponding cDNA sequence led to the
      identification of a putative exon that was not expressed in the cDNA. The
      identification of this putative exon raised the possibility that transcripts of
      the alpha 2(IV) gene may undergo alternative splicing. We have used a reverse
      transcriptase-polymerase chain reaction assay to establish that such alternative
      splicing does indeed occur. Our results show that the A. suum alpha 2(IV)
      collagen gene produces at least two similar, but not identical, transcripts via
      the selection of two alternative exons. Furthermore, this alternative splicing
      appears to be developmentally regulated, suggesting that alternative splicing may
      be used in order to modify the properties of type IV collagen during nematode
      development.

PMID- 8293876
TI  - Retinoic acid selectively promotes the survival and proliferation of neurogenic
      precursors in cultured neural crest cell populations.
AB  - The neural crest produces both neuronal and nonneuronal derivatives in response
      to a variety of environmental cues. Here, we have analyzed the effects of
      retinoic acid on the differentiative behavior of quail trunk neural crest cells
      in vitro. We show that retinoic acid selectively increases neurogenesis in
      cultured neural crest cell populations, probably by promoting the survival and
      stimulating the proliferation of neuronal precursors. Our results suggest that
      neural crest-derived neurogenic precursors are specific targets for retinoic acid
      in vitro and raise the possibility that retinoic acid promotes the generation of
      peripheral neurons in vivo.

PMID- 8293877
TI  - Neuronal potential of cells in early postnatal rat sciatic nerve.
AB  - A population of undifferentiated cells with neuronal potentialities were revealed
      in rat sciatic nerve. Explant cultures of sciatic nerve were prepared from
      newborn or early postnatal rat. Cultures were growth in F14 medium supplemented
      with 10% of fetal calf serum, incubated in a humidified 3% CO2, 97% air
      atmosphere. Within 2 weeks, refractile cells exhibiting the morphology of neurons
      were observed in all examined cultures. These cells had ovoid or multipolar
      refractile cells bodies with extended cytoplasmic processes. The neuronal nature
      of these cells was confirmed by their immunostaining with specific neuronal
      markers: neurofilament triplets, neuron-specific enolase, peripherin, microtubule
      associated proteins, and brain spectrin. This neuronal population displayed
      various phenotypes. The CO2 concentration in the incubator plays an important
      role, since the number of differentiated neurons was lower in cultures incubated
      in 5% CO2. Since the sciatic nerve is devoid of nerve cell bodies in vivo, we
      concluded that early postnatal sciatic nerve contains crest cells with neuronal
      potentialities differentiating into neurons in response to the culture's
      environmental cues.

PMID- 8293878
TI  - The prevention of smaller blastomeres of early Tubifex embryos from entering
      mitosis by unreplicated DNA.
AB  - The zygote of Tubifex divides unequally into a smaller AB-cell and a larger CD
      cell; the latter produces a smaller C-cell and a larger D-cell at its next
      division. The present study was undertaken to examine mitotic cycles in early
      Tubifex embryos whose DNA replication was blocked by aphidicolin. Although
      zygotes and larger blastomeres (i.e., CD- and D-cells) which contained
      unreplicated DNA entered mitosis on schedule, their smaller sister blastomeres
      (i.e., AB- and C-cells) were prevented from entering mitosis for 8 hr or more,
      viz. through three or more rounds of mitotic cycles of control cells. Whole-mount
      immunocytochemistry of microtubules confirmed that these smaller blastomeres were
      blocked at interphase. Entry into mitosis of smaller blastomeres which contained
      unreplicated DNA was significantly accelerated by caffeine. Among descendants of
      the D-quadrant containing unreplicated DNA, macromere 1D was the only cell that
      entered mitosis on schedule; its daughter cells 2d and 2D were no longer immune
      to aphidicolin-induced inhibition of mitosis. When CD-cells were induced to
      divide equally in the presence of aphidicolin, two daughter cells of individual
      CD-cells entered mitosis at the same time in about one-half of the cases or with
      a 20- to 60-min lag in the timing of the remaining cases, although their entry
      into mitosis lagged about 60 min behind that of the control cells. An examination
      of the distribution of pole plasms in these cells suggested that susceptibility
      to unreplicated DNA of blastomeres inversely correlates to the amount of pole
      plasm they inherit. These results suggest that Tubifex embryos contain a feedback
      pathway which couples the completion of DNA replication to the initiation of
      mitosis and that the replication feedback system operates in smaller blastomeres,
      but not in larger blastomeres of early Tubifex embryos.

PMID- 8293879
TI  - Analysis of cellular interactions involved in differential control of prestalk
      genes in Dictyostelium discoideum.
AB  - The prestalk-specific genes ecmA and ecmB in Dictyostelium are both induced by
      cAMP and DIF-1. In an attempt to understand the control mechanism of the
      differential expression of the two genes in multicellular aggregates, we examined
      the requirement for additional cellular interaction using low-cell-density
      cultures. We show that the whole process of inducing expression of these genes
      depends on high cell density. However, cells which have become responsive to DIF
      1 expressed both genes at a low cell density in the presence of DIF-1 when
      incubated in a medium previously conditioned by developing cells. 8-Br-cAMP,
      which is believed to penetrate the cell membrane and activate protein kinase A,
      induced ecmB, but not ecmA, in the absence of the conditioned medium. These
      results suggest that there may be a specific inducer of ecmB in the conditioned
      medium which acts via activation of protein kinase A. Previously, the two genes
      were shown to respond differently to cAMP in late development at high cell
      densities, where there were cellular interactions. However, cAMP given to low
      density-plated cells inhibited the conditioned medium-dependent induction of both
      genes to the same extent, suggesting that cAMP itself does not directly show the
      different effects on the two genes.

PMID- 8293880
TI  - Early skeletal muscle development proceeds normally in parthenogenetic mouse
      embryos.
AB  - In mouse chimeras with parthenogenetic cell contribution, the skeletal
      musculature appears to be largely devoid of parthenogenetically derived cells. To
      analyze the appearance and early distribution of myotomal cells in parthenotes,
      we determined the expression of the muscle-specific transcription factors
      myogenin, MYF-5, and MYF-6 by in situ hybridization in somites of Day 10 and 11
      embryos. Here, we report that these myogenic regulatory proteins are expressed in
      parthenogenetic animals together with desmin, one of the early muscle-specific
      structural proteins. We also show that parthenogenetic cells contribute equally
      to dermatome, sclerotome, and myotome in Day 10 and 11 chimeras. These results
      suggest that early myotomal cells expressing the myogenic control proteins
      develop and allocate normally in parthenogenetic embryos and in
      parthenogenetic<==>normal chimeras. The underrepresentation in older chimeras may
      therefore be due to selective elimination. These data also argue against
      imprinting of the myogenic factor genes myogenin, Myf-5, and Myf-6.

PMID- 8293881
TI  - Multiple portions of a small region of the Drosophila transformer gene are
      required for efficient in vivo sex-specific regulated RNA splicing and in vitro
      sex-lethal binding.
AB  - The transformer gene of Drosophila is regulated by Sex-lethal-dependent 3' splice
      site blockage. 40 nucleotides immediately upstream of the regulated splice site
      are sufficient to direct sex-specific regulated splicing in transgenic animals.
      This entire region appears to be necessary for regulation and for efficient Sex
      lethal binding. Natural splice sites containing partial homology to transformer
      do not show regulation. Mutations which replace the 16 nucleotides surrounding
      the branch point or alter single nucleotides near the splice site eliminate or
      reduce regulation without eliminating splicing. Mutations which reduce or
      eliminate regulation in vivo reduce binding to Sex-lethal in vitro, consistent
      with the hypothesis that these mutations bring about their effects by altering
      Sex-lethal binding rather than by altering binding sites for additional non-Sex
      lethal factors.

PMID- 8293882
TI  - The Einsteck-method: position and structure of projections formed by implants of
      a ventral character.
AB  - The behavior of colored beads and of various living tissues after implantation
      into the Xenopus blastocoel is investigated. It is confirmed that the location of
      a graft along the anteroposterior axis depends on its intrinsic anteroposterior
      character. Comparison with the behavior of the beads suggests that the final
      position can be achieved by movement of the graft around the dorsoventral
      circumference of the inner marginal zone during gastrulation. Ventral marginal
      explants, or animal caps treated with fibroblast growth factor, both form ventral
      vesicles if cultured in isolation, but in the implantation experiments they often
      yield projections containing segmented muscle blocks. This behavior does not
      occur when the axis of the host has been suppressed by ultraviolet irradiation
      and so it is concluded that it represents dorsalization of the graft by the host.
      The tail-like structures formed as a result of ventral-type tissue implantations
      do not contain neural tissue, while the mesodermal parts are typically of mixed
      graft and host origin.

PMID- 8293883
TI  - Evidence for sex transformation of germline cells in ovarian tumor mutants of
      Drosophila.
AB  - Mutations at a few genetic loci in Drosophila cause ovarian tumors with hundreds
      of poorly differentiated germ cells. We examined several of these mutants to test
      the hypothesis that such ovarian tumors contain sex-transformed cells. By testing
      for expression of male germline traits, we determined that partial germline sex
      transformation occurs in otu, snf, Sxlfs, and bam ovarian tumors. Thus these
      genes are likely to be required for proper establishment of germline sexual
      identity.

PMID- 8293884
TI  - Developmental specificity of a bidirectional moth chorion promoter in transgenic
      Drosophila.
AB  - The developmentally specific activity of the 326-bp promoter that is shared by
      the paired 18 and 401 chorion genes of the silkmoth Antheraea pernyi was studied
      in transgenic Drosophila melanogaster. Bidirectional activity of this promoter is
      demonstrated in a novel dual reporter vector, containing lacZ on one side and CAT
      on the other. The single chorion-specific hexamer of this promoter, TCACGT, is
      essential for expression in both orientations; even single-base substitutions (at
      positions 2 or 4 of the hexamer) suppress expression. With both reporter genes,
      ovarian expression is greater from the 401 side of the promoter, although the
      difference between the two sides is greater for the CAT gene. The intact promoter
      fragment (which includes some 5' untranslated sequences) is expressed with a high
      degree of tissue specificity, but a central 184-bp fragment derived from it is
      also active ectopically in parts of the internal male genitalia. Strong spatial
      as well as temporal regulation is evident with both the intact promoter and its
      184-bp subfragment, assayed in either orientation.

PMID- 8293885
TI  - Thyroid hormone-dependent regulation of the intestinal fatty acid-binding protein
      gene during amphibian metamorphosis.
AB  - To investigate, at the molecular level, the remodeling of small intestine during
      amphibian metamorphosis, a subtractive hybridization approach was used to
      identify genes that are differentially regulated by thyroid hormone. A frog cDNA
      was isolated from Xenopus laevis and determined to be the gene encoding the
      intestinal fatty acid-binding protein (IFABP) based on its high sequence homology
      to the previously cloned mammalian IFABP gene. Northern blot analyses and in situ
      hybridization histochemistry also showed that, like the mammalian IFABP genes,
      frog IFABP gene expression is restricted to the intestinal epithelium. Xenopus
      embryos express detectable IFABP mRNA at stage 33/34, suggesting that intestinal
      epithelial cells differentiate well before feeding begins at stage 45. Moreover,
      during metamorphosis, levels of IFABP mRNA were gradually down-regulated over a
      period of about 20 days between stages 54 and 62, reaching a minimum at
      metamorphic climax, after which they were reelevated as the secondary epithelium
      forms. This reduction in IFABP gene expression could be reproduced in only 3 days
      by treating premetamorphic tadpoles with thyroid hormone. Our findings also show
      that this effect, while likely to be indirect, takes place before overt
      morphological changes are evident in primary epithelial cells. Thus, the down
      regulation of IFABP mRNA is one of the early molecular events preceding
      epithelial cell death during intestinal remodeling.

PMID- 8293886
TI  - Keratinocytes are involved in regulating the developmental changes in the
      proliferative activity of mouse epidermal melanoblasts in serum-free culture.
AB  - When epidermal cell suspensions derived from 0.5-, 2.5-, and 4.5-day-old mice
      were plated onto uncoated polystyrene dishes and cultured with serum-free medium
      supplemented with dibutyryl cyclic adenosine 3',5'-monophosphate and basic
      fibroblast growth factor, melanoblasts proliferated dramatically around
      keratinocyte colonies and after 12-14 days pure and enriched cultures of
      melanoblasts (ca. 75%) and melanocytes (ca. 25%) were obtained. In contrast, when
      epidermal cell suspensions derived from 7.5-, 20.5-, and 60.5-day-old mice were
      cultured similarly, keratinocytes failed to attach to the dish and melanoblasts
      did not proliferate at all. However, when epidermal cell suspensions of older
      mice were plated onto type I collagen-coated dishes and cultured similarly,
      keratinocytes attached well to the dish and melanoblasts proliferated
      dramatically around keratinocyte colonies. Moreover, pure melanoblasts and
      melanocytes derived from primary cultures of young and old mice could be
      subcultured on collagen-coated dishes with the medium in the presence of
      secondary keratinocytes that were subcultured from a pure population of primary
      keratinocytes. No differences were observed in the proliferative activity of
      secondary melanoblasts between young and old mice. These results suggest that
      keratinocytes are involved in regulating the proliferation of mouse epidermal
      melanoblasts and that the developmental changes in the proliferative activity of
      epidermal melanoblasts in culture are due to the developmental changes in the
      substrate attachment and proliferation of keratinocytes, rather than to intrinsic
      changes in melanoblasts.

PMID- 8293887
TI  - lacZ expression in germline transgenic zebrafish can be detected in living
      embryos.
AB  - Use of transgenic technology in zebrafish has been limited by the inability to
      efficiently express transgenes in early embryos of F1 and subsequent generations
      and to rapidly detect transgenic fish. We generated transgenic fish by injecting
      fertilized eggs with the Escherichia coli lacZ gene under the control of the
      Xenopus elongation factor 1 alpha transcriptional regulatory element. Four of
      five lines of transgenic fish we obtained express the lacZ gene in early embryos.
      The pattern of expression was distinct for each line, with two lines showing
      extensive expression beginning at approximately the midblastula transition, one
      showing patchy expression and one showing expression almost exclusively in motor
      neurons. Expression patterns were stable through the F2 generation in the three
      lines studied to date. The availability of these lines facilitated the
      development of a reliable and rapid method for live-staining lacZ-expressing
      embryos using the substrate fluorescein-di-beta-D-galactopyranoside (FDG).
      Positive embryos of the two most highly lacZ-expressing lines could be identified
      after 2-3 min of staining in FDG and then picked out and raised. These
      observations should prove useful for a variety of studies in zebrafish.

PMID- 8293888
TI  - Autonomous expression of the nic1 acetylcholine receptor mutation in zebrafish
      muscle cells.
AB  - The nic1b107 (nic1) mutation blocks expression of both functional and clustered
      acetylcholine receptors (AChRs) in zebrafish muscle. Normally, signaling between
      motoneurons and muscles regulates AChR clustering. To learn if signaling is
      affected and to identify the primary cellular target of the nic1 mutation, we
      made mosaic embryos by transplanting motoneurons and muscle precursors from wild
      type to mutant embryos. Genotypically mutant muscle cells fail to cluster AChRs
      even when contacted by wild-type motoneurons, whereas genotypically mutant
      motoneurons induce AChR clustering on wild-type muscle cells. Moreover, mutant
      muscle cells fail to cluster AChRs under culture conditions that induce AChR
      clustering on wild-type cells. We conclude that the nic1 mutation acts
      autonomously in muscle cells rather than by affecting signaling between
      motoneurons and muscle. The wild-type nic1 gene is necessary in muscle for
      expression and clustering of AChRs.

PMID- 8293889
TI  - Effects of ciliary neurotrophic factor on the survival and response to nerve
      growth factor of cultured rat sympathetic neurons.
AB  - The development and maturation of cells depends not only on their genetic
      history, but also on sequences and combinations of environmental signals
      appropriate to their developmental age. Early postnatal rat sympathetic neurons
      are dependent on nerve growth factor (NGF) for survival in vivo and in vitro, but
      earlier sympathetic neuroblasts may not require NGF. Ciliary neurotrophic factor
      (CNTF) provides short-term in vitro trophic support to embryonic and neonatal
      sympathetic neurons, but its role in vivo is not understood. In this study we
      examined further the capability of CNTF to support neonatal rat superior cervical
      ganglion (SCG) sympathetic neurons in vitro and the effect of CNTF on the trophic
      activities of NGF. SCG neurons cultured with either CNTF or NGF survived for 24
      hr in low-density cultures depleted of nonneuronal cells, in contrast to neurons
      with neither factor. However, with CNTF only a fraction of the NGF-maintained
      number of neurons survived for 6 days. CNTF given in combination with NGF in
      these nonneuron-depleted cultures produced a significant decrease in the number
      of neurons surviving for 6 days, compared to the number supported by NGF alone.
      If such cultures were supplemented with Schwann cells, very different results
      were obtained: CNTF alone supported the 6-day survival of 80% as many neurons as
      did NGF, and the combination of CNTF with NGF produced no decrease in neuronal
      survival. Antibody to NGF did not block the support provided by CNTF and Schwann
      cells. Immunostaining for the low-affinity NGF receptor (LNGFR), intense in the
      NGF-supported neurons, was absent in the CNTF-supported neurons and reduced in
      the neurons exposed to the combination of NGF and CNTF. These results show that
      CNTF can act synergistically with a Schwann cell-derived agent to provide trophic
      support to neonatal sympathetic neurons, and that it can down-regulate the
      responsiveness of those neurons to NGF.

PMID- 8293890
TI  - Social rearing effects on HPA axis activity over early development and in
      response to stress in rhesus monkeys.
AB  - Previous studies have found evidence of behavioral and psychophysiological
      differences between nonhuman primates reared in different social environments,
      however, few of these have employed longitudinal study of the animals over early
      development. In this study, HPA axis activity was assessed via measurement of
      ACTH and cortisol values over the first 6 months of life and in response to two
      stressful housing transitions in 48 infant rhesus monkeys that were either mother
      or peer-reared. ACTH and cortisol values declined over the first 6 months in
      both rearing groups. Peer-reared monkeys showed lower levels of ACTH over the
      first 6 months of life than mother-reared, but the rearing groups did not differ
      in basal cortisol values over this period. Mother-reared animals showed a greater
      ACTH response to the mild stress of being moved to a new cage, and male monkeys
      showed higher values than females. Mother-reared animals showed the largest
      cortisol increase in response to the caging transition. Both groups showed
      increases in ACTH and cortisol in response to the more severe stress of
      separation from their rearing partners and housing with unfamiliar age-mates.
      Mother-reared animals again showed the largest increase in ACTH in response to
      these events, but increases in cortisol were similar among both sexes and rearing
      groups. These results suggest an interaction of sex and rearing history in
      response to stressful events.

PMID- 8293891
TI  - Developmental changes in chickens' masked thresholds.
AB  - Masked thresholds were estimated at four frequencies (.25, .5, 1, and 2 kHz) in
      three levels of broadband noise (approximately 0, 10, and 20 dB/Hz) in over 100
      chickens at 0 and 4 days of age. An adaptive procedure was based on delays in
      ongoing peeps that occurred when chicks heard the tones over the background
      noise. Masked thresholds decreased an average of 1 dB per day immediately after
      birth. This increasing sensitivity is more likely due to nonsensory factors,
      similar to distraction masking reported in human neonates, than to improving
      frequency resolution. Masked thresholds in these neonates are otherwise affected
      by spectrum level and frequency in the same way as the responses of mature
      subjects: thresholds increase by nearly 1 dB for each dB of increase in the
      spectrum level of the masker, and by approximately 3 dB for each octave of
      frequency. Thus, although elevated by some nonsensory effect, masked thresholds
      in newborn chicks are similar to those in humans.

PMID- 8293892
TI  - Beer, breast feeding, and folklore.
AB  - Beer consumption by nursing women altered the sensory qualities of their milk and
      the behavior of their infants during breast-feeding in the short term. The
      infants consumed significantly less milk during the 4-hr testing sessions in
      which their mothers drank alcoholic beer compared to when the mothers drank
      nonalcoholic beer; this decrease in milk intake was not due to a decrease in the
      number of times the babies fed. Although the infants consumed less of the alcohol
      flavored milk, the mothers believed their infants had ingested enough milk,
      reported that they experienced a letdown during nursing, and felt they had milk
      remaining in their breasts at the end of the majority of feedings. Moreover, the
      mothers terminated the feeds the same percentage of time on both testing days.
      The mechanism by which the consumption of alcoholic beer by lactating women
      decreases milk intake by their nurslings remains to be determined.

PMID- 8293893
TI  - Ontogeny of amicable social behavior in the mouse: gender differences and ongoing
      isolation outcomes.
AB  - The behavioral repertoire of male and female outbred CD-1 mice was characterized
      during development (postnatal Days 23-47). To assess the effects of the rearing
      condition, half of the subjects were individually housed (IC) at weaning (Day
      21), while the remaining mice were housed in pairs (PC) of same-sex siblings. The
      occurrence of 22 behavioral items was scored during nine social encounters, 3
      days apart, between pairs of unfamiliar same-sex and same-condition animals.
      Individually housed mice were much more involved than paired subjects in solitary
      play and social interactions (affiliative, investigative, and soliciting
      behaviors), while less interested in nonsocial behaviors (exploration, and escape
      oriented or maintenance activities). An over-days increment for elements of
      social behavior was evident, with a peak of affiliative behavior at 23-32 days of
      age. For gender differences, in contrast with rat data, a marked female primacy
      in both social and playful behaviors was found. Overall, these findings clearly
      indicate that the behavioral repertoire of developing mice during paired
      encounters is strongly affected by both the sex of the subjects and the housing
      condition they are experiencing.

PMID- 8293894
TI  - The effects of 24-hr maternal separation and of litter-size reduction on the
      isolation-distress response of 12-day-old rat pups.
AB  - We asked whether the mother-infant interaction acted over time to regulate the
      ultrasonic vocalization (USV) and activity responses of 12-day-old rat pups to
      isolation in a novel test area. In a series of four experiments, we found that 24
      hr of maternal deprivation did not alter USV isolation responses, but that
      reduction of litter size to 4 pups from 8 markedly attenuated the USV response
      and increased weight gain, without effects on activity level. Ambient
      temperatures during 24-hr maternal separation were varied from 23 degrees to 35
      degrees C without effect on subsequent USV responses, but activity levels were
      markedly reduced in pups separated at the low heat level. Possible mechanisms for
      maternal regulation of USV responses involving nutrient effects, altered
      processing of thermal stimuli, and the inhibition of thermogenesis by nutrient
      deprivation are discussed.

PMID- 8293895
TI  - Removal of stones from the bile duct at ERCP without sphincterotomy.
AB  - The main risks associated with endoscopic stone removal arise from the
      sphincterotomy that is performed to facilitate stone extraction. The complication
      rate may be higher when the bile duct is not dilated. Between January 30, 1990,
      and March 30, 1993, we attempted to remove stones up to 8 mm in diameter through
      the intact papilla, without performing sphincterotomy, in 24 patients. Nine
      patients underwent balloon dilation of the sphincter or of a low duct stricture
      to facilitate stone removal. All patients were treated successfully and are well
      at follow-up. Two patients (one having had balloon dilation of the sphincter) had
      mild pancreatitis that required 2 days in the hospital. During the same period,
      215 patients were treated for duct stones 8 mm or less through a standard
      sphincterotomy. Complications occurred in 11 of these patients: five episodes of
      pancreatitis, three infections, one perforation, and two other complications.
      Although these two groups of patients are not directly comparable, it appears
      that selected stones can be extracted from the bile duct without sphincterotomy
      with relative safety. This technique should be studied further, especially in
      younger persons where sphincter preservation may be desirable.

PMID- 8293896
TI  - Laser lithotripsy of difficult bile duct stones by means of a rhodamine-6G laser
      and an integrated automatic stone-tissue detection system.
AB  - This report describes the initial clinical implementation of a new laser
      lithotripter system capable of effective fragmentation of common bile duct stones
      with a high degree of safety provided by an integrated stone-tissue detection
      system. This system automatically terminates laser pulse transmission if tissue
      contact is sensed. Eighteen patients with giant or impacted common bile duct
      stones refractory to standard treatment techniques were treated via the
      endoscopic retrograde route using a rhodamine-6G dye laser with an integrated
      stone-tissue detection system. In the event of tissue contact, the stone-tissue
      detection system cuts off the laser pulse after 190 ns (after transmission of 5%
      to 8% of the total pulse energy). Nine patients were treated under
      cholangioscopic control, and nine patients were treated blindly under
      fluoroscopic control using only standard duodenoscopes with either a 6F standard
      endoscopic retrograde cholangiopancreatography catheter (4 patients), a 6.8F
      balloon catheter (3 patients), or a laser lithotriptor basket (2 patients). Laser
      induced fragmentation was achieved in all 18 patients (100%). Sixteen of 18
      patients (89%) became completely stone-free after completion of the treatment,
      including additional intracorporeal shock wave lithotripsy in five patients. The
      only major complications occurred in one fully anticoagulated patient with a
      prosthetic heart valve who developed significant hemobilia and transient
      cholangitis but recovered after conservative treatment. Laser lithotripsy using
      the rhodamine-6G dye laser plus stone-tissue detection system appears safe and
      effective and allows "blind" fragmentation of difficult common bile duct stones
      to be performed under radiologic control.

PMID- 8293897
TI  - Prospective evaluation of costs of disposable accessories in diagnostic and
      therapeutic ERCP.
AB  - Procedural (room fee) reimbursement from insurance payers is usually fixed for
      individual endoscopic procedures and may not include the costs of disposable
      equipment. This study estimated costs of disposable items used in ERCP procedures
      and calculated the percentage of total reimbursement spent on such equipment. A
      total of 248 ERCPs were performed in a 5-month study period, 192 (77%) of which
      were therapeutic. Total reimbursement was estimated to be $112,262 ($452 per
      procedure) and total disposable equipment costs were $47,195 ($190 per
      procedure), or 42% of total reimbursement. Disposable instrument costs in
      diagnostic ERCP approximated 13% of those associated with therapeutic ERCP, and
      the latter costs in turn utilized more than 60% of Medicare/Medicaid room fee
      reimbursement. This reimbursement may be inadequate to cover both disposable
      instrument costs and other procedural expenses, such as admit-recovery costs,
      nursing assistance, expenses related to endoscope purchase and capitalization,
      and equipment cleaning or sterilization. Our data suggest the need for either re
      usable endoscopic accessories or adequate compensation to cover disposable
      instrument costs.

PMID- 8293898
TI  - Randomized, prospective trial of direct current versus bipolar electrocoagulation
      for bleeding internal hemorrhoids.
AB  - Fifty patients with bleeding internal hemorrhoids unresponsive to 6 weeks of
      standard medical therapy were randomly assigned to receive treatment with direct
      current or bipolar electrocoagulation. Treatment groups were similar in bleeding
      severity and internal hemorrhoid grade. Treatment sessions were significantly
      longer for direct current electrocoagulation (8.8 +/- 0.2 minutes) than for
      bipolar electrocoagulation (0.1 +/- 0.03 minutes) (p < 0.001). When compared to
      the bipolar electrocoagulation group, direct current electrocoagulation patients
      had more procedural pain that terminated therapy (5 of 25 patients [20%] versus 0
      of 25 [0%], for a difference of 20% [95% confidence interval, 4% to 36%]; p =
      0.05) and prolonged pain after the procedure (4 of 25 patients [16%] versus 1 of
      25 [4%], for a difference of 12% [95% confidence interval, -4% to 28%]; p =
      0.35). However, more post-treatment rectal ulcerations were seen in the bipolar
      electrocoagulation-treated group (6 of 25 patients [24%] versus 1 of 25 [4%], for
      a difference of 20% [95% confidence interval, 2% to 38%]; p = 0.10). Treatment
      groups did not differ in number of treatment sessions or months of follow-up. The
      rates of success, defined as obliteration of the hemorrhoids or cessation of
      bleeding with reduction of the hemorrhoids to grade 1 or less, for the direct
      current electrocoagulation and the bipolar electrocoagulation groups were 88% and
      92%, respectively. Failures in the direct current electrocoagulation group were
      uncontrollable bleeding (n = 1) and refusal to continue therapy because of pain
      (n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293899
TI  - Electrosurgical safety of guide wires during endoscopic sphincterotomy.
AB  - A study was performed to determine whether alternate site electrosurgical burns
      could be caused by an inadequately insulated guide wire left in place during
      endoscopic papillotomy to maintain cannulation of the common bile duct. The
      safety of four covered guide wires and one standard guide wire was evaluated for
      electrosurgical safety. All four covered guide wires were coated with
      polyurethane or polytetrafluoroethylene (Teflon), providing insulation. Leakage
      currents under normal, limiting case, and fault (damaged insulation) conditions
      were compared to safety limits. All covered guide wires met safety limits under
      normal conditions, one of four covered guide wires met safety limits under
      limiting case conditions, and none met safety limits under fault conditions. The
      uncovered guide wire did not meet the safety limit under any conditions.
      CONCLUSION: Without a well-insulated guide wire with intact coating, our
      measurements indicate that leaving a guide wire in place during papillotomy may
      result in an electrosurgical burn.

PMID- 8293900
TI  - Post-cholecystectomy patients with "objective signs" of partial bile outflow
      obstruction: clinical characteristics, sphincter of Oddi manometry findings, and
      results of therapy.
AB  - Seventeen patients, 15 women and 2 men with upper abdominal pain categorized to
      biliary group I suspected sphincter of Oddi dysfunction, underwent thorough
      clinical evaluation including ERCP and endoscopic sphincter of Oddi manometry.
      All the patients were subsequently treated by endoscopic (n = 15) or surgical (n
      = 2) sphincterotomy. The mean age of patients studied was 62 years. They all had
      cholecystectomy several years previously (median, 18 years). At ERCP all patients
      showed a large common bile duct dilation (mean diameter, 18 mm) and delayed
      contrast drainage greater than 45 minutes. Sphincter of Oddi manometry, although
      abnormal in most patients, revealed normal sphincter of Oddi pressure in six
      patients (35%). Nonetheless, sphincterotomy resulted in relief of symptoms in all
      (mean follow-up, 28 months; range, 3 to 46 months), thus suggesting that their
      pain was indeed caused by the disordered sphincter of Oddi. These findings
      support the previous assumption that in symptomatic post-cholecystectomy patients
      the triad of elevated liver function tests, dilated common bile duct, and delayed
      contrast drainage at endoscopic retrograde cholangiopancreatography indicates a
      definitive sphincter of Oddi abnormality. The normal sphincter of Oddi pressures
      in many of these patients are probably due to a different, noncompliant type of
      sphincter of Oddi dysfunction. Because these patients invariably benefit from
      sphincterotomy, sphincter of Oddi manometry in this category is not only
      unnecessary, but it may also be misleading.

PMID- 8293901
TI  - A centering balloon for photodynamic therapy of esophageal cancer tested in a
      canine model.
AB  - Delivery of uniform circumferential light is desirable during photodynamic
      therapy of early or advanced esophageal cancer in human beings. Studies were
      performed in the canine esophagus to investigate whether use of a centering
      balloon would improve circumferential illumination of esophageal mucosa for
      photodynamic therapy of esophageal cancer. When the centering balloon was used,
      photodynamic therapy produced uniform and circumferential injury. With the
      cylindrical diffuser used in human studies, non-uniform and focal esophageal
      injury occurred. Placement of isotropic probes on the balloon wall allowed
      measurement and verification of relatively uniform light doses delivered to
      esophageal mucosa during balloon photodynamic therapy. The centering balloon has
      a potential role in improving light dosimetry during esophageal photodynamic
      therapy.

PMID- 8293902
TI  - Mediastinal lymph node detection with endosonography.
AB  - Eighty-two persons with chronic abdominal pain, submucosal or extrinsic masses,
      or achalasia and 20 volunteers without symptoms were prospectively examined with
      endosonography to assess the incidence and features of mediastinal
      lymphadenopathy. In 99 persons without malignant disease, 86% were found to have
      paraesophageal lymph nodes by endosonography. Overall, 352 lymph nodes were
      found, with a mean of 3.6 +/- 2.8 SD lymph nodes per person (range, 0 to 14 lymph
      nodes). Increasing age and chronic pancreatitis were found to correlate with a
      greater number of lymph nodes. Otherwise, clinical features including quantity of
      tobacco use, height, weight, sex, and race did not correlate with a greater
      number of lymph nodes as assessed by regression analysis. The mean width and
      length among the lymph nodes was 4.9 +/- 2.4 mm (range, 1 to 15 mm) and 9.9 +/-
      5.2 mm (range, 1 to 30 mm), respectively, with the largest lymph nodes occurring
      in the peritracheal and peribronchial regions. Of all subjects, 95% had a maximum
      lymph node width of 10 mm or less, but only 40% had a maximum lymph node length
      of 10 mm or less. The most common ultrasound features of these lymph nodes
      included a triangular or crescent-shaped and homogeneous or centrally echogenic
      pattern. These ultrasound characteristics were distinct from those previously
      described in malignant lymph nodes. In summary, a high background prevalence of
      mediastinal lymph nodes exists as detected by endosonography and must be
      considered when performing esophageal or lung carcinoma staging
      examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293903
TI  - Endoscopic stent exchange using a guide wire and mini-snare.

PMID- 8293904
TI  - A new method for exchange of endoprostheses in the biliary and pancreatic ducts.

PMID- 8293905
TI  - Dynamic fluorescence video endoscopy for intravital evaluation of
      gastrointestinal mucosal blood flow.

PMID- 8293906
TI  - Successful balloon dilation of achalasia during pregnancy.

PMID- 8293907
TI  - Treatment of symptomatic choledocholithiasis during pregnancy.

PMID- 8293908
TI  - Bilateral pneumothoraces and subcutaneous emphysema after endoscopic
      sphincterotomy.

PMID- 8293909
TI  - Massive gas spread through a duodenal perforation after endoscopic
      sphincterotomy.

PMID- 8293910
TI  - Pneumoperitoneum after insertion of endoscopic biliary stent for post
      cholecystectomy biliary leak.

PMID- 8293911
TI  - Duodenal Dieulafoy's lesion.

PMID- 8293912
TI  - Varices of the entire gastrointestinal tract.

PMID- 8293913
TI  - Injury to the liver and spleen after diagnostic ERCP.

PMID- 8293914
TI  - Benign duodenocolic fistula: an unusual case of gastrointestinal bleeding.

PMID- 8293915
TI  - Lymphoid nodular hyperplasia: an unusual finding at laparoscopic surgery for a
      suspected bleeding Meckel's diverticulum.

PMID- 8293916
TI  - Endoscopic balloon catheter removal of a rubber nipple causing complete duodenal
      obstruction.

PMID- 8293917
TI  - Endoscopic diagnosis of thermal injury to the laryngopharynx after crack cocaine
      ingestion.

PMID- 8293918
TI  - Outcomes and effectiveness research: the 1992 investigator conference of the
      American Society for Gastrointestinal Endoscopy.

PMID- 8293919
TI  - Disposable versus reusable ERCP equipment: the tip of the regulatory iceberg.

PMID- 8293920
TI  - Colonoscopy for colorectal cancer: too much, too little, just right. ASGE
      Distinguished Lecture 1993.

PMID- 8293921
TI  - Presidential prerogative--eclectic thoughts put to verse.

PMID- 8293922
TI  - Endoscopic polypectomy of a large duodenal carcinoid.

PMID- 8293923
TI  - Mechanical failure of an expandable biliary endoprosthesis.

PMID- 8293924
TI  - Esophageal perforation associated with polyethylene glycol electrolyte lavage
      solution.

PMID- 8293925
TI  - Stretching of PEG dilation catheters.

PMID- 8293926
TI  - Duodenal perforation after removal of swallowed tooth.

PMID- 8293927
TI  - Sensitivity of CLO test not affected by pre-immersion of biopsy forceps in
      formalin.

PMID- 8293928
TI  - Latex seal for leaky endoscope valve.

PMID- 8293929
TI  - Glutaraldehyde-induced proctitis after endorectal ultrasound examination: a
      higher risk of incidence than expected?

PMID- 8293930
TI  - Endoscopic removal of a penetrating surgical clip from the esophagus.

PMID- 8293931
TI  - Urinary incontinence associated with dysphagia.

PMID- 8293932
TI  - Post-inflammatory polyps of esophagus: a rare sequela of endoscopic injection
      sclerotherapy for esophageal varix.

PMID- 8293933
TI  - Guide wire breakage.

PMID- 8293934
TI  - Anastomotic strictures in Crohn's disease: a new field for therapeutic endoscopy.

PMID- 8293935
TI  - Stent fracture in malignant biliary obstruction.

PMID- 8293936
TI  - The case of the missing polyp.

PMID- 8293937
TI  - Endoscopic gastritis and duodenitis.

PMID- 8293938
TI  - [Effects of sleep on gonadotropin secretion].
AB  - Comparable to the period of adolescence in puberty, sleep exerts profound effects
      on the gonadotropin secretion in adult women. During the early follicular phase
      of the menstrual cycle, a slowing of the luteinising hormone (LH) pulse
      frequencies is concomitant with a rise in LH pulse amplitudes during sleep. A
      selective sleep-associated increase in opioidergic, but not in dopaminergic
      activity, may account for the decline in the LH pulse frequencies. Since
      pituitary gonadotropin responsiveness is virtually unchanged during sleep, the
      reasons for the enhanced LH pulse amplitudes remain unknown. Although the
      physiological meaning of this neuroendocrine manifestation is unexplained at
      present, the observed changes in the LH secretory profiles during sleep may
      represent close functional links between the endocrine secretion and the rest
      activity cycle of the brain.

PMID- 8293939
TI  - [Acute disease of the pelvis: differentiation between gynecologic and surgical
      cause].
AB  - An acute disorder of the lower abdomen requires early clarification, whether or
      not it is of gynaecological or surgical origin. With non-gynaecological
      affections, beside diverticulitis, Crohn's disease, perforations, bowel
      obstructions, yersiniosis, vascular diseases (acute embolism, thrombosis or
      dissection), urological disorders or hernias, acute appendicitis has firstly to
      be considered. The systematic use of the different diagnostic instruments is
      discussed.

PMID- 8293940
TI  - [Locoregional intra-arterial chemotherapy of primary incurable local recurrence
      of breast cancer].
AB  - Approximately one third of all local recurrences of breast cancer are incurable
      at the time of diagnosis. Locoregional intraarterial chemotherapy is one of the
      new therapy modalities besides laser therapy and combined
      radiotherapy/hyperthermia. The results of a phase I-II study, in which 15
      patients with advanced, partly pretreated local recurrences as well as 2 patients
      with T4N2/N3 tumours were included, are reported as follows. All in all, 39
      superselective intraarterial chemotherapy courses were carried out. Mitomycin (10
      mg) and Mitoxantrone (25 mg) were infused over 90 min. The side effects due to
      the catheter system were two haematomas and one thrombosis attributed to an
      insufficient heparin dose. Locally, the chemotherapy was well tolerated. One
      severe systemic side effect, a leucopenia WHO 4 degrees was observed. Nausea,
      thrombocytopenia and alopecia rates were low (7 x nausea 1 degree, 5 x
      thrombocytopenia 1 degree, 2 x thrombocytopenia 2 degrees, 2 x alopecia 1
      degree). 6 Complete remissions (3 x pCR, 3 x cCR) as well as 6 partial remissions
      and 5 no changes were found. We believe that this method, because of the low side
      effect profile and the temporary good results, represents a good alternative in
      otherwise incurable locoregional recurrence of breast carcinoma and in specified
      cases of locally advanced disease. 1 degree and 2 x thrombocytopenia 2 degrees, 2
      x alopecia 1 degree). Altogether, 6 complete remissions were found (3 x cCR, 3 x
      pCR), 6 partial remissions with 4 x no change occurred.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8293941
TI  - [Minimizing scar expansion using the B technique in form correction of the
      breast].
AB  - For the last two years, the B-technique has been used in mammaplasty to minimise
      the extent of scars, if the expected resection weight is 700 g or less. 33
      patients were operated by means of this technique. Scar formation and areola
      sensation were examined and compared with 188 patients operated by the techniques
      of McKissock, Strombeck or Pitanguy. 19 of those patients and 3 patients, who had
      been operated on by the B-technique, developed hypertrophic scars. The widths of
      the scars was significantly smaller after operation by the B-technique, than by
      other techniques. After operation by the B-technique, the areola sensation was
      unchanged in 67% compared to 46% after operation by above mentioned and other
      techniques. In cases, where the expected resection weight does not exceed 700 g,
      the B-technique is superior to other techniques, because the medial scars can be
      avoided.

PMID- 8293942
TI  - [Value of palpation findings in breast examination].
AB  - During a period of 3.5 years 13,214 patients were examined in a specialised
      breast clinic; 87% of the women had been referred by gynaecologists. 73% of the
      160 carcinomas discovered 65% of the 143 fibroadenomas and 32% of the 982 cysts
      were palpable. Among 2,355 patients with a positive palpation, a carcinoma was
      found only in 5% of cases, whilst a carcinoma was found in 0.4% of the 10,819
      patients with negative palpation. Therefore the use of apparatus in breast
      diagnosis is highly recommended both to avoid unnecessary surgery and to discover
      small cancers.

PMID- 8293943
TI  - [First use of a 3D video-endoscope in gynecology].
AB  - A new 3D-videoendoscope offers a three-dimensional visualisation of organs and
      anatomical structures during laparoscopy. This system consists of a
      stereoendoscope, two microchip cameras and an electronic control system. The use
      of liquid crystal (LC)-shutterglasses gives a three-dimensional impression to the
      examiner. The advantages of this 3D-videoendoscopic system are: exact preparation
      and more rapid application of endoscopic suturing techniques.

PMID- 8293944
TI  - [Does 3D sonography present new perspectives for gynecology and obstetrics?].
AB  - 3D-sonography opens a new chapter of ultrasound-imaging. The aim of our study
      was, to summarise our preliminary experiences in the clinical application of this
      method. One-hundred and fifty patients were investigated with the use of
      transabdominal transducers. The scanning is performed after targeting the three
      dimensional region by the volume box. The three planes are displayed
      simultaneously on the screen. Analysis can be performed on any possible plane
      within the stored volume (tomography). Surface imaging and transparent imaging
      can be calculated and displayed by a work-station. Three-dimensional ultrasound
      makes complete imaging and documentation of sonographically investigated
      structures feasible. The possibility of arbitrarily often repeatable systematic
      analyses without risk for the patient seems to be the more important advantage
      than statistical simultaneous imaging. Plastic imaging of structures, especially
      of foetuses, in the surface and transparent modes has been made possible for the
      first time. Biometry can also be measured in three dimensions (volumetry). Volume
      documentation provides the possibility of arbitrarily repeatable "real-time"
      scanning. By this means, any plane can be reanalyzed, remeasured and reassessed.
      This kind of documentation provides advantages in clinical, scientific, didactic
      and legal aspects. The first experiences with this new method seem to be
      promising. Further studies have to be conducted to evaluate the diagnostic
      significance of 3D-sonography in our field of specialisation.

PMID- 8293945
TI  - [Clinical documentation in obstetrics and collection of relevant data with
      reference to the structural reform law. Results of a survey of 72 clinics].
AB  - This study was conducted on the spread and usage of computer-aided software
      programme (GDS) in 72 obstetric departments. Standardised questionnaires were
      sent to universities and hospitals to ask for information on registered perinatal
      data. The record with the hand-written delivery book cannot record all data
      needed for quality protection as the PC is able to list. 89% of the obstetricians
      evaluate their clinical data regularly by statistical survey and classification.
      By analysing the general trend they can critically assess their actual
      obstetrical management. The PC is established in 83%, functions without technical
      problems in 92% and is optimal in the sequence of operation in 57% of all
      departments questioned. Overtime hours for the staff could be reduced in 11%, if
      a computer was used, and in 13% the nurses could take more care of mother and
      child because of less official red tape. Independent of the size of the
      department and the data processing knowledge of the staff, the software programme
      runs efficiently. The comprehensive basis data documentation with all perinatal
      and neonatal data is used to its full extent in 100% of the cases and documents
      the clinical effectivity. With regard to the standardised hospital quality
      control process by the modified requirements in the public health legislation,
      the directors of the hospital departments are able to assess the quality control
      and show economic independence.

PMID- 8293946
TI  - [Rescheduling genetic amniocentesis from the 16th to the 13th/14th week of
      pregnancy--report of experience].
AB  - At the ob/gy department of the Innsbruck University routine, genetic
      amniocentesis has been offered from the 13/14 week of gestation since 1991. In
      1991 44.5% of all amniocenteses were performed as early amniocentesis, it rose in
      1992 to 61.5%, the rest being performed in the 16th week of gestation. In a total
      of 346 genetic amniocenteses, 8 pathological karyotypes were obtained (six
      trisomies, one 47 XXY, one marker chromosome), six from samples obtained at early
      amniocentesis and two obtained at the 16th week. Three weeks following the
      procedure, a spontaneous abortion rate of 0.87% occurred. Cultivation took 1-2
      days longer with samples from early amniocentesis than with samples collected at
      the 16th week. In two cases the cultures failed and a repeat procedure had to be
      performed at the 16th week. With early amniocentesis performed at week 13/14
      results are known of gestation. The long period of anxiety, which many women see
      as a serious disadvantage of amniocentesis is thus significantly reduced.

PMID- 8293947
TI  - [Comparison of vaginal and abdominal ultrasound measurements with embryologic
      growth curves in early pregnancy].
AB  - Body lengths and chorionic diameters of 225 early pregnancies with known
      fertilisation age, measured by transvaginal sonography (TVS), were compared with
      measuring results of measurements from abdominal ultrasound and of embryological
      specimen from the literature. The TVS measuring results were made according to
      the Carnegie classification. It is shown that the growth curve obtained by TVS is
      very similar to valid embryological growth curves, although the "Greatest Length"
      (GL) is measured by sonography not the Crown-Rump-Length (CRL). Between the sixth
      and eighth gestational week, the TVS curve shows strong resemblance to abdomino
      sonographical curves. After that period, the TVS results tend to be
      systematically lower. The earliest TVS measurement of the human embryo in
      possible in the sixth gestational week, one week earlier than with abdominal
      ultrasound. There is a good correlation between the development of a structure
      and its earliest detection by TVS, active movements of the embryo can even be
      shown earlier than assumed by embryologists (stage 20/ninth week of gestation).
      Due to terminological reasons, in ultrasound the established term "Crown-Rump
      Length" should be replaced by "Greatest Length". In a TVS-examination of an
      embryo (gestational weeks 4 to 11), morphological criteria must be additional
      contributions to the determination of maturity and integrity of a pregnancy. The
      application of the specimen-derived Carnegie classification to TVS measurements
      seem to be possible, as well as the utilization of TVS results in embryology.

PMID- 8293948
TI  - [Psychoses in puerperium: symptoms, course and long-term prognosis].
AB  - 86 women who suffered from a psychotic disorder for the first time in their life
      within 6 weeks after parturition, were investigated regarding sociodemographic
      and gynaecological parameters, time of onset and initial symptomatology,
      psychopathological symptoms during hospitalisation, treatment and short-term
      outcome of the illness. The majority of patients became ill after the first
      (75%), full-term normal (63%) delivery and within the first two postpartum weeks
      (78%). The most frequent initial symptoms were anxiety, restlessness, depressive
      mood, sleep disturbances, behaviour disturbances, catatonic excitement, delusions
      and hallucinations. By the time of follow-up investigation, 16 women had died; 61
      women were investigated on average 25.6 years after onset (minimum 12, maximum 41
      years), using standardised instruments of evaluation. Nearly two-thirds of the
      patients had suffered re-manifestation of psychotic disorder during a long-term
      course (64%). The frequency of re-manifestations of illness after additional
      pregnancies and deliveries was found to be 1:4, which is also known to be the
      expected frequency during the course of other psychotic disorders. These results
      do not justify the global recommendation to avoid additional pregnancies or carry
      out an interruption of pregnancy, if the patient has a history of postpartum
      psychosis. The climacteric period also seems to be a vulnerable phase for the re
      manifestation of illness. Nearly 3/4 of the investigated women displayed no
      disturbances in any of the evaluated dimensions (psychopathological,
      psychological, psychosocial status) at the time of follow-up.

PMID- 8293949
TI  - [Sarcoma of the breast: what is the contribution of immunohistochemistry and flow
      cytometry?].
AB  - Only 0.2-1% of all mammary malignancies are sarcomas of the breast. This study
      includes 4 cases: 2 osteosarcomas, 1 fibrosarcoma, and 1 malignant
      undifferentiated stromal sarcoma. The therapy was mastectomy in 3 cases with
      dissection of axillary lymph nodes and simple mastectomy in one case. One patient
      demonstrated local recurrence and died. The remaining 3 patients developed
      neither metastases nor local recurrence. They are still alive after a follow-up
      period of between 18 months and 17 years. As first-line treatment, wide local
      excision or simple mastectomy is recommended. Dissection of the axillary
      lymphatics, adjuvant radiotherapy, or chemotherapy have no established value in
      the treatment of breast sarcoma. In our 4 cases, flow-cytometric analysis does
      not always agree with the biological properties of the tumour and the clinical
      behaviour, in contrast to the results obtained in respect of carcinomas.

PMID- 8293950
TI  - [Hormone treatment of sex disorders in menopause--causal therapy or placebo?].
AB  - Clinical reports on successful hormonal treatment of climacteric or menopausal
      sexual dysfunctions are in contradiction with the lack of oestrous phenomena in
      humans as well as with the results of double-blind studies finding no objective
      proof for the alleged hormonal influence. A review of recent studies on the topic
      showed, that apart from a critical threshold, hormones exert no influence on
      sexual behaviour that would go beyond the alleviation of vasomotoric or genital
      menopausal symptoms or their consequences. However, psychosocial and relational
      factors play a major role in sexual dysfunctions generally and at this age of the
      "empty nest" and a doctor-patient relationship based on trust may well help in
      coping with them. Finally, a (new?) understanding of genital sexuality as a
      concise body-language or literally an incarnation of the relationship is
      advocated and may add a new dimension and quality to a couple's sex life.

PMID- 8293951
TI  - [Society of Obstetrics and Gynecology in Berlin. 13 January 1993 meeting].

PMID- 8293952
TI  - Identification and sequence determination of the capsid protein gene of human
      astrovirus serotype 1.
AB  - We present the sequence of an open reading frame (ORF) at the 3' end of human
      astrovirus serotype 1. Primer extension experiments showed that the RNA
      expressing this gene is shorter than the complete ORF, and could form a protein
      of M(r) 85,540. The protein was expressed by recombinant baculovirus and was
      recognized by anti-virion serum, indicating a structural role. Sequence
      comparison indicates that astrovirus serotypes 1 and 2 differ markedly in the C
      terminal half of the protein but are well conserved towards the N-terminus.

PMID- 8293953
TI  - Vascular permeability enhancing activity of Porphyromonas gingivalis protease in
      guinea pigs.
AB  - Porphyromonas gingivalis protease, which had been isolated from a culture
      supernatant, caused vascular permeability enhancement in a dose-dependent manner
      when injected into guinea pig skin. The permeability-enhancing reaction caused by
      the protease was not affected by treatment with antihistamine, but was greatly
      augmented by simultaneous injection of a kinin potentiator, carboxypeptidase N
      inhibitor. However, the reaction was inhibited by soybean trypsin inhibitor or
      alpha 2-antiplasmin, although both of these inhibitors could not inhibit P.
      gingivalis protease at all by themselves. A bradykinin-degrading enzyme,
      carboxypeptidase B, weakened this vascular reaction. Results described indicate
      that the permeability-enhancing reaction induced by the protease is caused by
      activation, of the kallikrein-kinin cascade in the tissue.

PMID- 8293954
TI  - Rapid identification of streptomycetes by artificial neural network analysis of
      pyrolysis mass spectra.
AB  - An artificial neural network was trained to distinguish between three putatively
      novel species of Streptomyces using normalised, scaled prolysis mass spectra from
      three representative strains of each of the taxa, each sampled in triplicate.
      Once trained, the artificial neural network was challenged with spectral data
      from the original organisms, the 'training set', from additional members of the
      putative novel taxa and from over a hundred strains representing six other
      actinomycete genera. All of the streptomycetes were correctly identified but many
      of the other actinomycetes were mis-identified. A modified network topology was
      developed to recognise the mass spectral patterns of the non-streptomycete
      strains. The resultant neural network correctly identified the streptomycetes,
      whereas all of the remaining actinomycetes were recognised as unknown organisms.
      The improved artificial neural network provides a rapid, reliable and cost
      effective method of identifying members of the three target streptomycete taxa.

PMID- 8293956
TI  - Identification of a cryptic gene associated with an insertion sequence not
      previously identified in Bacillus thuringiensis.
AB  - After screening several Bt strains with a cryII toxin probe, clones from two
      strains were found to contain a cryptic cryIIB gene associated with an insertion
      sequence element belonging to the IS2/IS3 family. The lack of expression of this
      gene appears to result from mutation of the upstream orf2 gene which has been
      shown to be necessary for cryII expression.

PMID- 8293955
TI  - Characterization of a Bacillus thuringiensis strain which is toxic to the
      housefly Musca domestica.
AB  - A Bacillus thuringiensis isolate has been discovered which is toxic to the common
      housefly (Musca domestica) as well as other Diptera and Lepidoptera. Crystal
      delta-endotoxins purified from this isolate killed 50% of Musca larvae at a
      concentration of 10.2 micrograms/ml, and beta-exotoxin was not detected. Sodium
      dodecyl polyacrylamide gel electrophoresis of the purified crystals revealed
      three protein species which were related to CryIA(b), CryIB and CryIIA toxins on
      the basis of immunoreactivity and amino-terminal sequence determination. Southern
      blot and DNA restriction analyses suggested that the strain has sequences related
      to one cryIA(b), one cryIIA, and two cryIIB genes.

PMID- 8293957
TI  - Inhibition of coaggregation between Porphyromonas gingivalis and Streptococcus
      oralis by fibrinogen fragments.
AB  - The localization of regions of fibrinogen that inhibit coaggregation between
      Porphyromonas gingivalis and Streptococcus oralis was investigated. The
      coaggregation was inhibited by A alpha and gamma chains, but not by B beta chain.
      The inhibitory activity of fragment D was more potent than that of fragment E.
      Some cyanogen bromide-treated fragments isolated from A alpha and gamma chains
      including the NH2-terminal 148-207 amino acid residues of A alpha chain (A alpha
      148-207) and gamma 1-78 showed inhibitory activities. A alpha 148-207 was further
      digested with lysyl endopeptidase. A alpha 158-176 and A alpha 192-206 which
      contained four and two arginine residues, respectively, retained the inhibitory
      activities. When the arginine residues of these two peptides were modified by
      phenylglyoxal, the inhibitory activities were much reduced. These findings
      suggest that the arginine residues of some specific regions of fibrinogen may
      play an important role in the inhibition of the coaggregation.

PMID- 8293958
TI  - Induction of aerial mycelium formation in a bld mutant of Streptomyces tendae by
      borrelidin--a macrolide antibiotic.
AB  - In a screening programme for substances with morphogenic effects on the
      nikkomycin producer strain Streptomyces tendae Tu 901 we identified a metabolite,
      which induced aerial mycelium formation in the bld mutant Tu 901/S 2566-EM 1. By
      using a HPLC UV/Vis absorbance spectral library we could confirm that this
      compound was identical with the macrolide antibiotic borrelidin. 100 ng
      borrelidin/paperdisc were sufficient to show an evident morphological effect.

PMID- 8293959
TI  - Genetic mapping in Bacillus subtilis 168 of the aadK gene which encodes
      aminoglycoside 6-adenylyltransferase.
AB  - Bacillus subtilis 168 has an aadK gene, which encodes aminoglycoside 6
      adenylyltransferase, a streptomycin-modifying enzyme, on its chromosome. To
      characterize the aadK gene, we constructed a B. subtilis 168 strain that carried
      the chloramphenicol resistance gene near the aadK on the chromosome and an aadK
      deletion mutant using an integration technique. The aadK gene was mapped between
      azlB and pheA on the chromosome of B. subtilis 168. The aadK deletion mutant was
      slightly more susceptible to streptomycin than the original strain. The result
      indicates that the aadK gene contributes low-level resistance to streptomycin in
      B. subtilis 168.

PMID- 8293960
TI  - Isolation and sequence analysis of the pmi gene encoding phosphomannose isomerase
      of Streptococcus mutans.
AB  - A gene encoding a phosphomannose isomerase from Streptococcus mutans GS-5 was
      identified immediately downstream from the fructokinase gene, scrK. Nucleotide
      sequence analysis of this region revealed an open reading frame (ORF) specifying
      a putative protein of 316 amino acids. The gene cloned in Escherichia coli
      expressed strong phosphomannose isomerase activity. The deduced amino acid
      sequence of the pmi gene has no significant similarity with any of the previously
      reported phosphomannose isomerase enzymes. Insertional inactivation of the
      upstream gene, scrK, in S. mutans also drastically reduced phosphomannose
      isomerase activity and the ability of the organism to utilize mannose as a sole
      carbon source. These results suggest that the S. mutans pmi gene constitutes an
      operon with the scrK gene.

PMID- 8293961
TI  - Activation of bovine plasminogen by Streptococcus uberis.
AB  - Culture filtrate from Streptococcus uberis was found to activate bovine and
      equine plasminogen but not that from rabbit, human or porcine plasma. In
      contrast, streptokinase from a Lancefield group C Streptococcus activated human
      plasminogen but not that from bovine, porcine and rabbit plasma. Very slight
      activity was observed against equine plasminogen. Plasmin was detected by
      hydrolysis of skimmed milk protein in agarose. The activation of bovine
      plasminogen by S. uberis culture filtrate resulted in the formation of three
      polypeptides with molecular masses of 56, 26 and 21 kDa. This is the first report
      of a streptokinase activity from this species.

PMID- 8293962
TI  - Sulfonate-sulfur assimilation by yeasts resembles that of bacteria.
AB  - Three sulfonates were tested for their ability to serve as nutrients for
      Hansenula wingei, Rhodotorula glutinis, Trigonopsis variabilis and Saccharomyces
      cerevisiae. Cysteate, taurine and isethionate, under aerobic conditions, could be
      utilized as sources of sulfur, although in some instances final cell yields were
      less than those obtained with an equimolar amount of sulfate-sulfur. Sulfonate
      assimilation by S. cerevisiae resembled that of bacteria (reported earlier by us)
      in several aspects: first, sulfate-S was used in preference to that of sulfonate,
      when both were present; second, mutants unable to use sulfate as a source of
      sulfur because of deficiencies in ATP sulfurylase, adenylylsulfate kinase (APS
      kinase) or PAPS reductase were able to utilize sulfonates; and third, mutants
      deficient in sulfite reductase were unable to utilize sulfonates.

PMID- 8293963
TI  - Rumen contents as a reservoir of enterohemorrhagic Escherichia coli.
AB  - We investigated the role of the rumen fermentation as a barrier to the foodborne
      pathogen, Escherichia coli O157:H7. Strains of E. coli, including several
      isolates of O157:H7, grew poorly in media which simulated the ruminal environment
      of a well-fed animal. Strains of E. coli O157:H7 did not display a superior
      tolerance to ruminal conditions which may facilitate their colonization of the
      bovine digestive tract. Unrestricted growth of E. coli was observed in rumen
      fluid collected from fasted cattle. Growth was inhibited by rumen fluid collected
      from well-fed animals. Well-fed animals appear less likely to become reservoirs
      for pathogenic E. coli. These results have implications for cattle slaughter
      practices and epidemiological studies of E. coli O157:H7.

PMID- 8293964
TI  - Two different types of fosfomycin resistance in clinical isolates of Klebsiella
      pneumoniae.
AB  - The fosfomycin susceptibility of 100 clinical isolates of Klebsiella pneumoniae
      and the resistance mechanisms utilized by resistant strains were examined. Washed
      cells prepared from the strains demonstrating MICs of more than 8 micrograms ml-1
      of fosfomycin inactivated the drug. A crude extract from strain Tf129B, highly
      resistant to fosfomycin, was used to study the enzymatic properties of the drug
      inactivating enzyme. The optimum pH for inactivation was 7.8 and the optimum
      temperature of the reaction was 37 degrees C. Glutathione was shown to be
      effective as a cofactor in the inactivation. It was suggested that the
      inactivating enzyme of Klebsiella pneumoniae was fosfomycin: glutathione-S
      transferase, a constitutive enzyme located in the periplasmic space. A good
      correlation was found between the specific activities of this enzyme and the MIC
      levels; however, certain strains showed a low level of fosfomycin:glutathione-S
      transferase activity which could not account for the increased MIC. Strains
      Tf129B and Tf408E, both demonstrating MICs of more than 1024 micrograms ml-1 of
      fosfomycin carried a transferable resistance plasmid. In strain Tf129B, the
      mechanism of fosfomycin resistance was due to a high level of enzymic activity.
      In strain Tf408E, it was determined to be mainly due to the reduced permeability
      of the cell membrane.

PMID- 8293965
TI  - Effect of miconazole on the structure and function of plasma membrane of Candida
      albicans.
AB  - The primary mode of action of azoles is the inhibition of cytochrome P-450
      dependent 14 alpha-demethylase, a key enzyme in ergosterol biosynthesis in fungi.
      Our results demonstrated that Candida albicans cells grown in the presence of 10
      micrograms ml-1 of miconazole (miconazole-grown), do not possess ergosterol in
      their plasma membranes and this ergosterol depletion leads to a drastic change in
      membrane fluidity as shown by fluorescence polarization measurements and
      unsaturation index. There was an increase in membrane order in miconazole-grown
      cells and a reduced rate of uptake of amino acids. We also checked for membrane
      permeability changes in normal mid-log phase cells (normal-grown) in short
      incubations (10 min) with 10 micrograms ml-1 miconazole (miconazole-incubated).
      Interestingly, the amino acid uptake rates except that of Gly were not affected
      significantly in these cells. The results suggest that in the miconazole
      incubated cells, the drug is not able to alter the level of ergosterol or inhibit
      ergosterol biosynthesis during 10 min incubation and therefore the interaction of
      the drug neither leads to significant disorganization of membrane components, nor
      affects permease activity, whereas in the miconazole-grown cells there is
      ergosterol depletion leading to accumulation of biosynthetic intermediates,
      resulting in membrane rearrangement thereby causing a major fluidity change. This
      fluidity change may explain the drastic reduction of amino acid transport in
      miconazole-grown cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293966
TI  - Application of polymerase chain reaction with specific and arbitrary primers to
      identification and differentiation of Leishmania parasites.
AB  - Two oligonucleotide primers Lsmc1 and Lsmv1 derived from the conserved and the
      variable region of a major class kinetoplast DNA (kDNA) minicircle (pLURkE3) of
      Leishmania strain UR6 were used for the polymerase chain reaction (PCR) in order
      to amplify a 461-bp fragment from the kDNAs of different Leishmania species.
      These primers amplify the specific fragment from the kDNAs of cutaneous species
      only. The cutaneous species can further be distinguished by randomly amplified
      polymorphic DNA (RAPD) analysis of the kDNAs of these organisms using arbitrarily
      chosen oligonucleotides. The arbitrary primers also generate polymorphic DNA
      fingerprints at the genomic level with different L. donovani isolates. The
      results indicate that the PCR and arbitrarily primed PCR (AP-PCR) may be
      extremely useful approaches for identifying and distinguishing Leishmania
      parasites.

PMID- 8293967
TI  - Meiosis as an "M" thing: twenty-five years of meiotic mutants in Drosophila.

PMID- 8293968
TI  - Mutational analysis of a C-dependent late promoter of bacteriophage Mu.
AB  - Late transcription of bacteriophage Mu initiates at four promoters, P(lys), PI,
      PP and Pmom, and requires the Mu C protein and the host RNA polymerase. Promoter
      containing DNA fragments extending approximately 200 bp upstream and downstream
      of the 5' starts of the lys, I and P transcripts were cloned into a multicopy
      lacZ-expression plasmid. Promoter activity, assayed by beta-galactosidase
      expression, was determined under two different conditions: (1) with C provided
      from a compatible plasmid in the absence of other Mu factors and (2) with C
      provided from an induced Mu prophage. beta-galactosidase activities were greatest
      for P(lys), intermediate for PI, and lowest for PP. Similar analysis of plasmids
      containing nested sets of deletions removing 5' or 3' sequences of P(lys)
      demonstrated that a 68-bp region was sufficient for full activity. Point
      mutations were generated within the 68-bp region by mutagenic oligonucleotide
      directed PCR (Mod-PCR). Properties of the lys promoter mutants indicated that, in
      addition to the -10 region, a 19-bp region from -52 to -34 containing the C
      footprint is required for C-dependent promoter activity.

PMID- 8293969
TI  - A sister-strand exchange mechanism for recA-independent deletion of repeated DNA
      sequences in Escherichia coli.
AB  - In the genomes of many organisms, deletions arise between tandemly repeated DNA
      sequences of lengths ranging from several kilobases to only a few nucleotides.
      Using a plasmid-based assay for deletion of a 787-bp tandem repeat, we have found
      that a recA-independent mechanism contributes substantially to the deletion
      process of even this large region of homology. No Escherichia coli recombination
      gene tested, including recA, had greater than a fivefold effect on deletion
      rates. The recA-independence of deletion formation is also observed with
      constructions present on the chromosome. RecA promotes synapsis and transfer of
      homologous DNA strands in vitro and is indispensable for intermolecular
      recombination events in vivo measured after conjugation. Because deletion
      formation in E. coli shows little or no dependence on recA, it has been assumed
      that homologous recombination contributes little to the deletion process.
      However, we have found recA-independent deletion products suggestive of
      reciprocal crossovers when branch migration in the cell is inhibited by a ruvA
      mutation. We propose a model for recA-independent crossovers between replicating
      sister strands, which can also explain deletion or amplification of repeated
      sequences. We suggest that this process may be initiated as post-replicational
      DNA repair; subsequent strand misalignment at repeated sequences leads to genetic
      rearrangements.

PMID- 8293970
TI  - Use of high and low level overexpression plasmids to test mutant alleles of the
      recF gene of Escherichia coli K-12 for partial activity.
AB  - We showed that sufficient overexpression of the wild-type recF gene interfered
      with three normal cell functions: (1) UV induction of transcription from the LexA
      protein-repressed sulA promoter, (2) UV resistance and (3) cell viability at 42
      degrees. To show this, we altered a low-level overexpressing recF+ plasmid with a
      set of structurally neutral mutations that increased the rate of expression of
      recF. The resulting high-level overexpressing plasmid interfered with UV
      induction of the sulA promoter, as did the low-level overexpressing plasmid. It
      also reduced UV resistance more than its low level progenitor and decreased
      viability at 42 degrees, an effect not seen with the low-level plasmid. We used
      the high-level plasmid to test four recF structural mutations for residual
      activity. The structural alleles consisted of an insertion mutation, two single
      amino acid substitution mutations and a double amino acid substitution mutation.
      On the Escherichia coli chromosome the three substitution mutations acted
      similarly to a recF deletion in reducing UV resistance in a recB21 recC22 sbcB15
      sbcC201 genetic background. By this test, therefore, all three appeared to be
      null alleles. Measurements of conjugational recombination revealed, however, that
      the three substitution mutations may have residual activity. On the high-level
      overexpressing plasmid all three substitution mutations definitely showed partial
      activity. By contrast, the insertion mutation on the high-level overexpressing
      plasmid showed no partial activity and can be considered a true null mutation.
      One of the substitutions, recF143, showed a property attributable to a leaky
      mutation. Another substitution, recF4101, may block selectively two of the three
      interference phenotypes, thus allowing us to infer a mechanism for them.

PMID- 8293971
TI  - Genetic and molecular characterization of GAL83: its interaction and similarities
      with other genes involved in glucose repression in Saccharomyces cerevisiae.
AB  - Expression of the GAL genes of Saccharomyces cerevisiae is subject to glucose
      repression, a global regulatory mechanism that requires several gene products. We
      have isolated GAL83, one of these genes required for glucose repression. The
      sequence of the predicted Gal83 protein is homologous to two other yeast
      proteins, Sip1p and Sip2p, which are known to interact with the SNF1 gene
      product, a protein kinase required for expression of the GAL genes. High-copy
      clones of SIP1 and SIP2 cross-complement the GAL83-2000 mutation (as well as
      GAL82-1, a mutation in another gene involved in glucose repression), suggesting
      that these four genes may perform similar functions in glucose repression.
      Consistent with this hypothesis, a gal83 null mutation does not affect glucose
      repression, and only dominant or partially dominant mutations exist in GAL83 (and
      GAL82). Two other observations were made that suggests that GAL83 functions
      interdependently with GAL82 and REG1 (another gene involved in glucose
      repression) to effect glucose repression: 1) REG1 on a low-copy plasmid cross
      complements GAL82-1 and GAL83-2000 mutations, and 2) all pairwise combinations of
      reg1, GAL82-1 and GAL83-2000 fail to complement one another. Such unlinked
      noncomplementation suggests that Gal83p, Gal82p and Reg1p may interact with one
      another. Possible roles for GAL83, GAL82 and REG1 are discussed in relation to
      SNF1, SIP1 and SIP2.

PMID- 8293972
TI  - Mutations that suppress the deletion of an upstream activating sequence in yeast:
      involvement of a protein kinase and histone H3 in repressing transcription in
      vivo.
AB  - Regulated transcription of most protein-encoding genes in Saccharomyces
      cerevisiae requires an upstream activating sequence (UAS); in the absence of UAS
      elements, little or no transcription occurs. In certain mutant strains, however,
      promoters that have been deleted for their UAS can direct significant levels of
      transcription, indicating that the remaining promoter elements (the basal
      promoter) are capable of directing higher levels of transcription, but they are
      normally represented in wild-type strains. To analyze this repression, we have
      selected for mutations that cause increased transcription of the SUC2 gene in the
      absence of its UAS. In addition to some previously studied genes, this selection
      has identified five genes that we have designated BUR1, BUR2, BUR3, BUR5 and BUR6
      (for Bypass UAS Requirement). The bur mutations cause pleiotropic phenotypes,
      indicating that they affect transcription of many genes. Furthermore, some bur
      mutations suppress the requirement for the SNF5 trans-activator at both SUC2 and
      Ty. Additional analysis has demonstrated that BUR1 is identical to SGV1, which
      encodes a CDC28-related protein kinase. This result indicates that protein
      phosphorylation is important for repression of the SUC2 basal promoter as well as
      other aspects of transcription in vivo. Finally, BUR5 is identical to HHT1,
      encoding histone H3, further implicating chromatin structure as important for
      expression of SUC2.

PMID- 8293973
TI  - Isolation and characterization of chromosome-gain and increase-in-ploidy mutants
      in yeast.
AB  - We have developed a colony papillation assay for monitoring the copy number of
      genetically marked chromosomes II and III in Saccharomyces cerevisiae. The unique
      feature of this assay is that it allows detection of a gain of the marked
      chromosomes even if there is a gain of the entire set of chromosomes (increase-in
      ploidy). This assay was used to screen for chromosome-gain or increase-in-ploidy
      mutants. Five complementation groups have been defined for recessive mutations
      that confer an increase-in-ploidy (ipl) phenotype, which, in each case,
      cosegregates with a temperature-sensitive growth phenotype. Four new alleles of
      CDC31, which is required for spindle pole body duplication, were also recovered
      from this screen. Temperature-shift experiments with ipl1 cells show that they
      suffer severe nondisjunction at 37 degrees. Similar experiments with ipl2 cells
      show that they gain entire sets of chromosomes and become arrested as unbudded
      cells at 37 degrees. Molecular cloning and genetic mapping show that IPL1 is a
      newly identified gene, whereas IPL2 is allelic to BEM2, which is required for
      normal bud growth.

PMID- 8293974
TI  - Mutations that enhance the cap2 null mutant phenotype in Saccharomyces cerevisiae
      affect the actin cytoskeleton, morphogenesis and pattern of growth.
AB  - Mutations conferring synthetic lethality in combination with null mutations in
      CAP2, the gene encoding the beta subunit of capping protein of Saccharomyces
      cerevisiae, were obtained in a colony color assay. Monogenic inheritance was
      found for four mutations, which were attributed to three genetic loci. One
      mutation, sac6-69, is in the gene encoding fimbrin, another actin-binding
      protein, which was expected because null mutations in SAC6 and CAP2 are known to
      be synthetic-lethal. The other two loci were designated slc for synthetic
      lethality with cap2. These loci include the mutations slc1-66, slc1-87 and slc2
      107. The slc mutations are semi-dominant, as shown by incomplete complementation
      in slc/SLC cap2/cap2 heterozygotes. The slc mutations and sac6-69 interact with
      each other, as shown by enhanced phenotypes in diheterozygotes. Moreover, the
      haploid slc2-107 sac6-69 double mutant is inviable. In a CAP2 background, the slc
      mutations lead to temperature and osmotic sensitivity. They alter the
      distribution of the actin cytoskeleton, including deficits in the presence of
      actin cables and the polarization of cortical actin patches. The slc mutations
      also lead to a pseudomycelial growth pattern. Together these results suggest that
      slc1 and slc2 encode components of the actin cytoskeleton in yeast and that the
      actin cytoskeleton can regulate the patterns of growth.

PMID- 8293975
TI  - A gene with specific and global effects on recombination of sequences from
      tandemly repeated genes in Saccharomyces cerevisiae.
AB  - The preservation of sequence homogeneity and copy number of tandemly repeated
      genes may require specific mechanisms or regulation of recombination. We have
      identified mutations that specifically affect recombination among natural
      repetitions in the yeast Saccharomyces cerevisiae. The rrm3 mutation stimulates
      mitotic recombination in the naturally occurring tandem repeats of the rDNA and
      copper chelatin (CUP1) genes. This mutation does not affect recombination of
      several other types of repeated genes tested including Ty elements, mating type
      information and duplications created by transformation. In addition to
      stimulating exchange among the multiple CUP1 repeats at their natural chromosomal
      location, rrm3 also increases recombination of a duplication of CUP1 units
      present at his4. This suggests that the RRM3 gene may encode a sequence-specific
      factor that contributes to a global suppression of mitotic exchange in sequences
      that can be maintained as tandem arrays.

PMID- 8293976
TI  - Molecular genetics of cryptopleurine resistance in Saccharomyces cerevisiae:
      expression of a ribosomal protein gene family.
AB  - The Saccharomyces cerevisiae CRY1 gene encodes the 40S ribosomal subunit protein
      rp59 and confers sensitivity to the protein synthesis inhibitor cryptopleurine. A
      yeast strain containing the cry1-delta 1::URA3 null allele is viable,
      cryptopleurine sensitive (CryS), and expresses rp59 mRNA, suggesting that there
      is a second functional CRY gene. The CRY2 gene has been isolated from a yeast
      genomic library cloned in bacteriophage lambda, using a CRY1 DNA probe. The DNA
      sequence of the CRY2 gene contains an open reading frame encoding ribosomal
      protein 59 that differs at five residues from rp59 encoded by the CRY1 gene. The
      CRY2 gene was mapped to the left arm of chromosome X, centromere-proximal to cdc6
      and immediately adjacent to ribosomal protein genes RPS24A and RPL46. Ribosomal
      protein 59 is an essential protein; upon sporulation of a diploid doubly
      heterozygous for cry1-delta 2::TRP1 cry2-delta 1::LEU2 null alleles, no spore
      clones containing both null alleles were recovered. Several results indicate that
      CRY2 is expressed, but at lower levels than CRY1: (1) Introduction of CRY2 on
      high copy plasmids into CryR yeast of genotype cry1 CRY2 confers a CryS
      phenotype. Transformation of these CryR yeast with CRY2 on a low copy CEN plasmid
      does not confer a CryS phenotype. (2) Haploids containing the cry1-delta 2::TRP1
      null allele have a deficit of 40S ribosomal subunits, but cry2-delta 1::LEU2
      strains have wild-type amounts of 40S ribosomal subunits. (3) CRY2 mRNA is
      present at lower levels than CRY1 mRNA. (4) Higher levels of beta-galactosidase
      are expressed from a CRY1-lacZ gene fusion than from a CRY2-lacZ gene fusion.
      Mutations that alter or eliminate the last amino acid of rp59 encoded by either
      CRY1 or CRY2 result in resistance to cryptopleurine. Because CRY2 (and cry2) is
      expressed at lower levels than CRY1 (and cry1), the CryR phenotype of cry2
      mutants is only expressed in strains containing a cry1-delta null allele.

PMID- 8293977
TI  - Genetic and phenotypic studies of hypomorphic lin-12 mutants in Caenorhabditis
      elegans.
AB  - The lin-12 gene of Caenorhabditis elegans is thought to encode a receptor for
      intercellular signals that specify certain cell fates during development. We
      describe several alleles of lin-12 that reduce but do not eliminate lin-12
      activity (hypomorphic alleles). These alleles cause a novel egg-laying defective
      (Egl) phenotype in hermaphrodites as well as incompletely penetrant cell fate
      transformations seen with high penetrance in lin-12 null mutants.
      Characterization of the Egl phenotype revealed additional roles of lin-12 in the
      development of the egg-laying system that were not apparent from studying lin-12
      null mutants: lin-12 activity is required for proper early vulval morphogenesis
      as well as for some unknown later aspect of egg-laying system development.
      Reversion of the Egl phenotype caused by one lin-12 hypomorphic allele was used
      to identify potential interacting genes as described in the accompanying paper.

PMID- 8293978
TI  - Suppressors of a lin-12 hypomorph define genes that interact with both lin-12 and
      glp-1 in Caenorhabditis elegans.
AB  - The lin-12 gene of Caenorhabditis elegans is thought to encode a receptor which
      mediates cell-cell interactions required to specify certain cell fates. Reversion
      of the egg-laying defective phenotype caused by a hypomorphic lin-12 allele
      identified rare extragenic suppressor mutations in five genes, sel-1, sel-9, sel
      10, sel-11 and sel(ar40) (sel = suppressor and/or enhancer of lin-12). Mutations
      in each of these sel genes suppress defects associated with reduced lin-12
      activity, and enhance at least one defect associated with elevated lin-12
      activity. None of the sel mutations cause any obvious phenotype in a wild-type
      background. Gene dosage experiments suggest that sel-1 and sel(ar40) mutations
      are reduction-of-function mutations, while sel-9 and sel-11 mutations are gain-of
      function mutations. sel-1, sel-9, sel-11 and sel(ar40) mutations do not suppress
      amorphic lin-12 alleles, while sel-10 mutations are able to bypass partially the
      requirement for lin-12 activity in at least one cell fate decision. sel-1, sel-9,
      sel-10, sel-11 and sel(ar40) mutations are also able to suppress the maternal
      effect lethality caused by a partial loss-of-function allele of glp-1, a gene
      that is both structurally and functionally related to lin-12. These sel genes may
      therefore function in both lin-12 and glp-1 mediated cell fate decisions.

PMID- 8293979
TI  - Cytotype control of Drosophila melanogaster P element transposition: genomic
      position determines maternal repression.
AB  - P element transposition in Drosophila is controlled by the cytotype regulatory
      state: in P cytotype, transposition is repressed, whereas in M cytotype,
      transposition can occur. P cytotype is determined by a combination of maternally
      inherited factors and chromosomal P elements in the zygote. Transformant strains
      containing single elements that encoded the 66-kD P element protein zygotically
      repressed transposition, but did not display the maternal repression
      characteristic of P cytotype. Upon mobilization to new genomic positions, some of
      these repressor elements showed significant maternal repression of transposition
      in genetic assays, involving a true maternal effect. Thus, the genomic position
      of repressor elements can determine the maternal vs. zygotic inheritance of P
      cytotype. Immunoblotting experiments indicate that this genomic position effect
      does not operate solely by controlling the expression level of the 66-kD
      repressor protein during oogenesis. Likewise, P element derivatives containing
      the hsp26 maternal regulator sequence expressed high levels of the 66-kD protein
      during oogenesis, but showed no detectable maternal repression. These data
      suggest that the location of a repressor element in the genome may determine
      maternal inheritance of P cytotype by a mechanism involving more than the overall
      level of expression of the 66-kD protein in the ovary.

PMID- 8293980
TI  - Deletion scanning of the regulatory sequences of the Fbp1 gene of Drosophila
      melanogaster using P transposase-induced deficiencies.
AB  - A procedure permitting deletion scanning of potential cis-regulatory sequences
      within a transgene whose genomic position remains fixed was applied to the study
      of the upstream sequences of the ecdysteroid-inducible Fat-body-protein-1 (Fbp1)
      gene. Deficiencies were induced in a Fbp1:Adh fusion transgene by means of a
      secondary P transposase mutagenesis. Phenotypic and molecular screens were used
      to select mutant transposons that retained their original genomic location and
      carried a deletion affecting the Fbp1 sequences but not the Adh reporter gene.
      Molecular mapping of the deletion breakpoints was achieved by sequence analysis
      and expression of the reporter gene was quantified by measurement of ADH
      activity. This procedure was efficient in detecting cis-acting elements, even
      those with moderate effects on levels of gene expression. For example, we have
      succeeded in identifying a negative regulatory element. Deletion of this element
      leads to a 50% increase in the reporter ADH activity. This element binds the
      transcription factor AEF-1. In addition, we have detected a strong, positively
      acting element contained within a 32-bp region located immediately upstream of an
      ecdysone-response element.

PMID- 8293981
TI  - Identification of genomic regions required for DNA replication during Drosophila
      embryogenesis.
AB  - A collection of Drosophila deficiency stocks was examined by bromodeoxyuridine
      (BrdU) labeling of embryos to analyze the DNA replication patterns in late
      embryogenesis. This permitted us to screen 34% of the genome for genes that when
      absent in homozygous deficiencies affect the cell cycle or DNA replication. We
      found three genomic intervals that when deleted result in cessation of DNA
      replication in the embryo, 39D2-3;E2-F1, 51E and 75C5-7;F1. Embryos deleted for
      the 75C5-7;F1 region stop DNA replication at the time in embryogenesis when a G1
      phase is added to the mitotic cell cycle and the larval tissues begin to become
      polytene. Thus, this interval may contain a gene controlling these cell cycle
      transitions. DNA replication arrests earlier in embryos homozygous for deletions
      for the other two regions. Analysis of the effects of deletions in the 39D2-3;E2
      F1 region on DNA replication showed that the block to DNA replication correlates
      with deletion of the histone genes. We were able to identify a single, lethal
      complementation group in 51E, l(2)51Ec, that is responsible for the cessation of
      replication observed in this interval. Deficiencies that removed one of the
      Drosophila cdc2 genes and the cyclin A gene had no effect on replication during
      embryogenesis. Additionally, our analysis identified a gene, pimples, that is
      required for the proper completion of mitosis in the post-blastoderm divisions of
      the embryo.

PMID- 8293982
TI  - Temperature sensitivity of negative segregation distortion in Drosophila
      melanogaster.
AB  - Previous work has shown that the direction of segregation distortion in the SD
      (Segregation Distorter) system in Drosophila melanogaster can sometimes be
      reversed, but this was found only with rather weak distorters and the effect was
      not large. The present study reports large negative segregation distortion in a
      strong distorter, SD-72 chromosome. In the presence of a specific X chromosome,
      supp-X(SD), the proportion, k, of SD-72 chromosomes recovered from the SD-72/cn
      bw males ranges from 0.99 at 20 degrees to 0.11 at 28.5 degrees, whereas with a
      standard-X chromosome, k ranges from 0.99 to 0.95 for the same temperature range.
      The temperature-sensitive period is during spermiogenesis. Using a mating system
      in which the sperm supply is nearly exhausted, it was shown that the negative
      distortion at high temperatures is due to an absolute reduction in the number of
      SD-72 chromosomes and an absolute increase in the number of cn bw chromosomes
      recovered. After adjusting for non-SD-related temperature effects, the amount of
      decrease in the number of SD-72 progeny is nearly the same as the amount of
      increase in the number of cn bw progeny, suggesting that the dysfunction switches
      from a spermatid carrying one homolog to one carrying the other. Negative
      distortion requires a radical revision of current hypotheses for the mechanism of
      segregation distortion and a possible modification of the current model is
      suggested, based on differential recovery of dysfunction in the two homologs
      during spermiogenesis.

PMID- 8293983
TI  - Effect of a founder event on variation in the genetic sex-determining system of
      the fire ant Solenopsis invicta.
AB  - Effects of a recent founder event on genetic diversity in wild populations of the
      fire ant Solenopsis invicta were studied, with particular attention given to the
      genetic sex-determining system. Diploid males are far more common relative to
      haploid males in introduced populations than in native populations of fire ants,
      and queens that produce diploid males account for a significantly larger
      proportion of the mated queens in introduced than in native populations.
      Differences between native and introduced populations in attributes of the mating
      systems (i.e., queen mating frequency or level of inbreeding) can be excluded as
      factors contributing to these different levels of diploid male production. Thus,
      we conclude that diploid males have increased in frequency in introduced
      populations because of a loss of allelic diversity at the sex-determining locus
      (loci). This loss of sex alleles has generated a substantial increase in the
      estimated segregational genetic load associated with production of sterile
      diploid males in introduced populations over the load in native populations. The
      loss of allelic diversity in the sex-determining system in introduced S. invicta
      is paralleled by a loss of electrophoretically detectable rare alleles at protein
      encoding loci. Such concordance between these different types of markers is
      predicted because each of the many sex alleles present in the native populations
      is expected to be rare. Estimates of expected heterozygosity (Hexp) based on 76
      electrophoretic loci do not differ significantly between the native and
      introduced fire ant populations, illustrating the lack of sensitivity of this
      measure for detecting many types of bottlenecks.

PMID- 8293984
TI  - Estimation of genotype distributions and posterior genotype probabilities for
      beta-mannosidosis in Salers cattle.
AB  - beta-Mannosidosis is a lethal lysosomal storage disease inherited as an autosomal
      recessive in man, cattle and goats. Laboratory assay data of plasma beta
      mannosidase activity represent a mixture of homozygous normal and carrier
      genotype distributions in a proportion determined by genotype frequency. A
      maximum likelihood approach employing data transformations for each genotype
      distribution and assuming a diallelic model of inheritance is described.
      Estimates of the transformation and genotype distribution parameters, gene
      frequency, genotype fitness and carrier probability were obtained simultaneously
      from a sample of 2,812 observations on U.S. purebred Salers cattle with enzyme
      activity, age, gender, month of pregnancy, month of testing, and parents
      identified. Transformations to normality were not required, estimated gene and
      carrier genotype frequencies of 0.074 and 0.148 were high, and the estimated
      relative fitness of heterozygotes was 1.36. The apparent overdominance in fitness
      may be due to a nonrandom sampling of progeny genotypes within families. The mean
      of plasma enzyme activity was higher for males than females, higher in winter
      months, lower in summer months and decreased with increased age. Estimates of
      carrier probabilities indicate that the test is most effective when animals are
      sampled as calves, although effectiveness of the plasma assay was less for males
      than females. Test effectiveness was enhanced through averaging repeated assays
      of enzyme activity on each animal. Our approach contributes to medical
      diagnostics in several ways. Rather than assume underlying normality for the
      distributions comprising the mixture, we estimate transformations to normality
      for each genotype distribution simultaneously with all other model parameters.
      This process also excludes potential biases due to data preadjustment for
      systematic effects. We also provide a method for partitioning phenotypic
      variation within each genotypic distribution which allows an assessment of the
      value of repeat measurements of the predictive variable for genotype assignment.

PMID- 8293985
TI  - Unusual mitochondrial genome organization in cytoplasmic male sterile common bean
      and the nature of cytoplasmic reversion to fertility.
AB  - Spontaneous reversion to pollen fertility and fertility restoration by the
      nuclear gene Fr in cytoplasmic male sterile common bean (Phaseolus vulgaris L.)
      are associated with the loss of a large portion of the mitochondrial genome. To
      understand better the molecular events responsible for this DNA loss, we have
      constructed a physical map of the mitochondrial genome of a stable fertile
      revertant line, WPR-3, and the cytoplasmic male sterile line (CMS-Sprite) from
      which it was derived. This involved a cosmid clone walking strategy with
      comparative DNA gel blot hybridizations. Mapping data suggested that the simplest
      model for the structure of the CMS-Sprite genome consists of three autonomous
      chromosomes differing only in short, unique regions. The unique region contained
      on one of these chromosomes is the male sterility-associated 3-kb sequence
      designated pvs. Based on genomic environments surrounding repeated sequences, we
      predict that chromosomes can undergo intra- and intermolecular recombination. The
      mitochondrial genome of the revertant line appeared to contain only two of the
      three chromosomes; the region containing the pvs sequence was absent. Therefore,
      the process of spontaneous cytoplasmic reversion to fertility likely involves the
      disappearance of an entire mitochondrial chromosome. This model is supported by
      the fact that we detected no evidence of recombination, excision or deletion
      events within the revertant genome that could account for the loss of a large
      segment of mitochondrial DNA.

PMID- 8293986
TI  - Molecular characterization of duplicate cytosolic phosphoglucose isomerase genes
      in Clarkia and comparison to the single gene in Arabidopsis.
AB  - The nucleotide sequence of PgiC1-a which encodes a cytosolic isozymes of
      phosphoglucose isomerase (PGIC; EC 5.3.1.9) in Clarkia lewisii, a wildflower
      native to California, is described and compared to the previously published
      sequence of the duplicate PgiC2-a from the same genome. Both genes have the same
      structure of 23 exons and 22 introns located in identical positions, and they
      encode proteins of 569 amino acids. Exon and inferred protein sequences of the
      two genes are 96.4% and 97.2% identical, respectively. Intron sequences are 88.2%
      identical. The high nucleotide similarity of the two genes is consistent with
      previous genetic and biosystematic findings that suggest the duplication arose
      within Clarkia. A partial sequence of PgiC2-b was also obtained. It is 99.5%
      identical to PgiC2-a in exons and 99.7% in introns. The nucleotide sequence of
      the single PgiC from Arabidopsis thaliana was also determined for comparison to
      the Clarkia genes. The A. thaliana PgiC has 21 introns located at positions
      identical to those in Clarkia PgiC1 and PgiC2, but lacks the intron that divides
      Clarkia exons 21 and 22. The A. thaliana PGIC protein is shorter, with 560 amino
      acids, and differs by about 17% from the Clarkia PGICs. The PgiC in A. thaliana
      was mapped to a site 20 cM from restriction fragment length polymorphism marker
      331 on chromosome 5.

PMID- 8293987
TI  - A note on the estimation of the effective number of additive and dominant loci
      contributing to quantitative variation.
AB  - A method of estimating the number of loci contributing to quantitative variation
      has been proposed by S. Wright in 1921. The method makes use of the means of
      inbred lines and the variances of their F1, F2 and backcrosses. The method has
      been extended to crosses between outbreeding populations by R. Lande in 1981.
      Additive gene action is one of the major assumptions required for obtaining valid
      estimates. It is shown here that this assumption may be relaxed. One can estimate
      both a total number of effective loci and a number of dominant loci (the latter
      only when the parents are inbred) by comparing the variances of the F1, F2 and
      backcrosses. Numerical illustrations are given, based on crossbreeding data.

PMID- 8293988
TI  - A computer simulation study of VNTR population genetics: constrained
      recombination rules out the infinite alleles model.
AB  - Extensive allelic diversity in variable numbers of tandem repeats (VNTRs) has
      been discovered in the human genome. For population genetic studies of VNTRs,
      such as forensic applications, it is important to know whether a neutral mutation
      drift balance of VNTR polymorphism can be represented by the infinite alleles
      model. The assumption of the infinite alleles model that each new mutant is
      unique is very likely to be violated by unequal sister chromatid exchange (USCE),
      the primary process believed to generate VNTR mutants. We show that increasing
      both mutation rates and misalignment constraint for intrachromosomal
      recombination in a computer simulation model reduces simulated VNTR diversity
      below the expectations of the infinite alleles model. Maximal constraint,
      represented as slippage of single repeats, reduces simulated VNTR diversity to
      levels expected from the stepwise mutation model. Although misalignment rule is
      the more important variable, mutation rate also has an effect. At moderate rates
      of USCE, simulated VNTR diversity fluctuates around infinite alleles expectation.
      However, if rates of USCE are high, as for hypervariable VNTRs, simulated VNTR
      diversity is consistently lower than predicted by the infinite alleles model.
      This has been observed for many VNTRs and accounted for by technical problems in
      distinguishing alleles of neighboring size classes. We use sampling theory to
      confirm the intrinsically poor fit to the infinite alleles model of both
      simulated VNTR diversity and observed VNTR polymorphisms sampled from two Papua
      New Guinean populations.

PMID- 8293989
TI  - Evolutionary dynamics of spore killers.
AB  - Spore killing in ascomycetes is a special form of segregation distortion. When a
      strain with the Killer genotype is crossed to a Sensitive type, spore killing is
      expressed by asci with only half the number of ascospores as usual, all surviving
      ascospores being of the Killer type. Using population genetic modeling, this
      paper explores conditions for invasion of Spore killers and for polymorphism of
      Killers, Sensitives and Resistants (which neither kill, nor get killed), as found
      in natural populations. The models show that a population with only Killers and
      Sensitives can never be stable. The invasion of Killers and stable polymorphism
      only occur if Killers have some additional advantage during the process of spore
      killing. This may be due to the effects of local sib competition or some kind of
      "heterozygous" advantage in the stage of ascospore formation or in the short
      diploid stage of the life cycle. This form of segregation distortion appears to
      be essentially different from other, well-investigated forms, and more field data
      are needed for a better understanding of spore killing.

PMID- 8293990
TI  - Molecular definition of the PAS1-1 mutation which affects silencing in
      Saccharomyces cerevisiae.

PMID- 8293991
TI  - Analysis of the stabilization system of pSM19035-derived plasmid pBT233 in
      Bacillus subtilis.
AB  - The low-copy-number, 9.0-kb pSM19035-derived plasmid pBT233, is stably inherited
      in Bacillus subtilis. The complete nucleotide (nt) sequence of pBT233 has been
      determined. Analysis of the nt sequence revealed nine major open reading frames
      (orfs). The repS, erm1 and erm2 genes have been assigned to three of these orfs,
      and given the gene order, repS-orf alpha-orf beta-orf gamma-orf delta-orf epsilon
      orf zeta-erm2-erm1. The organization of genes of the repS-orf gamma region
      resembles the organization of genes in the repE-orfI region of pAM beta 1.
      Messenger RNA species of molecular weights corresponding to repS, orf alpha + orf
      beta, orf gamma, orf delta and orf epsilon + orf zeta were detected by Northern
      blotting. Proteins of 23.8, 81.3, 34.4, 10.7 and 32.4 kDa correspond to Orfs
      beta, gamma, delta, epsilon and zeta, respectively. Bands of radioactive proteins
      of 25, 81, 34, 10 and 32 kDa were detected using the T7 promoter-expression
      system. The orf beta and orf gamma encode proteins that share homology to site
      specific recombinases and type-I topoisomerases, respectively. The orfs, delta,
      epsilon and zeta, encode proteins with unknown activity. Deletion of a 1.5-kb
      segment (nt 2999-4552) with coding capacity for orf beta, orf gamma and orf delta
      does not seem to affect plasmid maintenance. Removal of a 3.0-kb fragment (nt
      4598-7689) with coding capacity for orf epsilon and orf zeta reduced plasmid
      segregational stability, but deletion of a 5.2-kb DNA segment (nt 2546-7826)
      abolished it.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8293992
TI  - The DNA polymerase-encoding gene of African swine fever virus: sequence and
      transcriptional analysis.
AB  - The putative DNA polymerase-encoding gene of African swine fever virus has been
      sequenced. The gene, designated G1207R, is located in the central region of the
      viral genome, and encodes a protein of 1207 amino acids (aa) with a predicted
      M(r) of 139,835. The gene is transcribed at both early and late stages of
      infection into a 4.1-kb RNA. Transcription is initiated at tsp, 8 nucleotides
      (nt) upstream from the start codon. Open reading frame (ORF) G1207R contains four
      direct repeats in tandem close to the 3'-end. Each repeat consists of 12 nt,
      coding for the reiterated sequence, K/NPAG. The deduced aa sequence of G1207R
      shows significant similarity with DNA polymerases from cellular and viral origin,
      belonging to the alpha-like family of DNA polymerases. In particular, the G1207R
      protein presents a colinear arrangement of all the 3'-->5' exonuclease and
      polymerization highly conserved aa regions characteristic of this group of DNA
      dependent DNA polymerases.

PMID- 8293993
TI  - The intracellular production and secretion of HIV-1 envelope protein in the
      methylotrophic yeast Pichia pastoris.
AB  - The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein, gp120
      (ENV), is required in large quantities for immunological studies and as a
      potential vaccine component. We have expressed the DNA encoding gp120 in a highly
      efficient expression system based on the methylotrophic yeast, Pichia pastoris.
      The native gene was found to contain a sequence which resembled a Saccharomyces
      cerevisiae polyadenylation consensus and acted as a premature polyadenylation
      site in P. pastoris, resulting in the production of truncated mRNA. As full
      length mRNA was produced in S. cerevisiae, this indicates differences in mRNA 3'
      end formation between the two yeasts. Inactivation of this site by site-directed
      mutagenesis revealed several additional fortuitous polyadenylation sites within
      the gene. We have designed and constructed a 69%-synthetic gene with increased G
      + C content which overcomes this transcriptional problem, giving rise to full
      length mRNA. High levels of intracellular, insoluble, unglycosylated ENV were
      produced [1.25 mg/ml in high-density (2 x 10(10) cells per ml) fermentations].
      ENV also was secreted from P. pastoris using the S. cerevisiae alpha-factor
      prepro secretion leader and the S. cerevisiae invertase signal sequence. However,
      a high proportion of the secreted product was found to be hyperglycosylated, in
      contrast to other foreign proteins secreted from P. pastoris. There also was
      substantial proteolytic degradation, but this was minimized by maintaining a low
      pH on induction. Insoluble, yeast-derived ENV proteins are being considered as
      vaccine antigens and the P. pastoris system offers an efficient method of
      production.

PMID- 8293994
TI  - Comparative analysis of the sequence and structure of two Drosophila melanogaster
      genes encoding vitelline membrane proteins.
AB  - Two Drosophila melanogaster vitelline membrane protein-encoding genes (VM),
      located at polytene band positions 26A and 34C, have been cloned and
      comparatively characterized at the nucleotide level. Sequence analysis of genomic
      and cDNA clones for the two genes, VM26A.1 and VM34C.1, indicates that both are
      similarly organized with a central highly conserved domain [Scherer et al., Dev.
      Biol. 130 (1988) 786-788] which is flanked by unrelated regions, and that both
      genes lack introns. Comparison of the upstream regions reveals that both VM genes
      contain a hepatmeric element identical to one associated with the D. melanogaster
      yolk protein-encoding genes (YP). This heptamer occurs in the specific 5'
      flanking region responsible for ovarian temporal- and tissue-specific control in
      both VM and YP genes. A putative chorion transcription factor 2 site is also
      associated with an upstream control element of VM26A.1, but not with any
      sequenced portion of VM34C.1.

PMID- 8293995
TI  - Stable transformation of mosquito cell lines using a hsp70::neo fusion gene.
AB  - Mosquito cell culture transfection will allow the advancement of genetic studies
      of these important disease-transmitting insects. Towards this end, we report the
      generation of stably transformed Aedes aegypti Mos20 cells using a plasmid
      construct containing the Tn5 neo gene, the Drosophila melanogaster hsp70
      promoter, an SV40 intron and poly adenylation sequence, and a pBR 322 backbone.
      The apparent frequency of transfection, as measured by transient resistance of
      cell colonies to Geneticin (G418), ranged between 1 x 10(-4) and 1 x 10(-5),
      whereas the mean frequency of transformation, as assessed by establishment of
      cloned lines, was 3.3 x 10(-6). The stable cell lines display typical
      characteristics common to mammalian cell lines transformed with plasmids,
      including stable resistance to G418 after removal of selection, and co
      transformation with unlinked plasmids. However, in contrast to the report of
      transformation of Ae. albopictus cells [Monroe et al., Proc. Natl. Acad. Sci. USA
      89 (1992) 5725-5729], the plasmids within transformed Ae. aegypti cells have a
      wide range of copy number (3 to 5000), are extensively rearranged, and are only
      found integrated into the chromosome.

PMID- 8293996
TI  - Analysis of a transfer region from the staphylococcal conjugative plasmid pSK41.
AB  - The nucleotide sequence of a 14.4-kb region (tra) associated with DNA transfer of
      the staphylococcal conjugative plasmid, pSK41, has been determined. Analysis of
      the sequence revealed the presence of 15 genes potentially involved in the
      conjugative process. Polypeptide products likely to correspond to ten of these
      genes have been identified, of which one was found to be a lipoprotein.
      Comparison of the deduced tra products to the protein databases revealed several
      interesting similarities, one of which suggests an evolutionary link between this
      Gram+ bacterial conjugation system and DNA transfer systems of Gram- bacteria,
      such as Escherichia coli and Agrobacterium tumefaciens. The nt sequence also
      provided an insight into the transcriptional organisation and regulation of the
      region.

PMID- 8293997
TI  - Epstein-Barr virus-based vectors that replicate in rodent cells.
AB  - Vectors based on Epstein-Barr virus (EBV) have been useful for cloning and gene
      expression studies in primate cells. However, these vectors do not replicate in
      rodent cells. We demonstrate here that the addition of large fragments of
      mammalian DNA to vectors containing the EBNA-1 gene (encoding the Epstein-Barr
      nuclear antigen-1) and the family of repeats from EBV generates autonomously
      replicating vectors which are stably maintained as extrachromosomal plasmids in
      hamster cells. By using a density-shift assay in Cs2SO4 density gradients, we
      demonstrate that the plasmids replicate once per cell cycle at high efficiency.
      These plasmids represent, for rodent cells, the only available class of stable,
      autonomous vectors replicating once per cell cycle. It is likely that this type
      of EBV-based autonomous replication system can also be extended to other
      organisms for which stable, extrachromosomal plasmid systems are not available.

PMID- 8293998
TI  - Genomic sequences of murine gamma B- and gamma C-crystallin-encoding genes:
      promoter analysis and complete evolutionary pattern of mouse, rat and human gamma
      crystallins.
AB  - The murine genes, gamma B-cry and gamma C-cry, encoding the gamma B- and gamma C
      crystallins, were isolated from a genomic DNA library. The complete nucleotide
      (nt) sequences of both genes were determined from 661 and 711 bp, respectively,
      upstream from the first exon to the corresponding polyadenylation sites,
      comprising more than 2650 and 2890 bp, respectively. The new sequences were
      compared to the partial cDNA sequences available for the murine gamma B-cry and
      gamma C-cry, as well as to the corresponding genomic sequences from rat and man,
      at both the nt and predicted amino acid (aa) sequence levels. In the gamma B-cry
      promoter region, a canonical CCAAT-box, a TATA-box, putative NF-I and C/EBP sites
      were detected. An R-repeat is inserted 366 bp upstream from the transcription
      start point. In contrast, the gamma C-cry promoter does not contain a CCAAT-box,
      but some other putative binding sites for transcription factors (AP-2, UBP-1, LBP
      1) were located by computer analysis. The promoter regions of all six gamma-cry
      from mouse, rat and human, except human psi gamma F-cry, were analyzed for common
      sequence elements. A complex sequence element of about 70-80 bp was found in the
      proximal promoter, which contains a gamma-cry-specific and almost invariant
      sequence (crygpel) of 14 nt, and ends with the also invariant TATA-box. Within
      the complex sequence element, a minimum of three further features specific for
      the gamma A-, gamma B- and gamma D/E/F-cry genes can be defined, at least two of
      which were recently shown to be functional. In addition to these four sequence
      elements, a subtype-specific structure of inverted repeats with different-sized
      spacers can be deduced from the multiple sequence alignment. A phylogenetic
      analysis based on the promoter region, as well as the complete exon 3 of all
      gamma-cry from mouse, rat and man, suggests separation of only five gamma-cry
      subtypes (gamma A-, gamma B-, gamma C-, gamma D- and gamma E/F-cry) prior to
      species separation.

PMID- 8293999
TI  - A human DNA segment encompassing leucine and methionine tRNA pseudogenes
      localized on chromosome 6.
AB  - A human genomic clone, designated LHtlm8, that strongly hybridized to a mammalian
      leucine tRNA(IAG) probe, was found to encompass a pair of tRNA pseudogenes that
      are transcribed in a homologous cell extract. A leucine tRNA(AAG) pseudogene
      (TRLP1) is 2.1-kb upstream and of opposite polarity to a methionine elongator
      tRNA(CAU) pseudogene (TRMEP1). TRLP1 has three nucleotide variations (97%
      identity) from its cognate leucine tRNA(IAG), while TRMEP1 has a 78% identity
      with its cognate tRNA. Similar to a number of other eukaryotic tRNA pseudogenes,
      presumptive precursor tRNA transcripts are generated from the two pseudogenes in
      vitro, but possibly due to their aberrant and unstable secondary and tertiary
      structures, no detectable mature tRNA products are observed. The two tRNA
      pseudogenes are encompassed within a 9.6-kb EcoRI fragment that has been assigned
      to the chromosomal locus, 6pter-q13, by Southern blot hybridization of human
      rodent somatic cell hybrid DNAs with probes derived from the cloned tRNA
      pseudogenes and flanking sequences. A 4.4-kb EcoRI fragment also harbored in
      clone LHtlm8 was mapped to human chromosome 11, suggesting that the two EcoRI
      fragments were inadvertantly ligated together during construction of the genomic
      library.

PMID- 8294000
TI  - Cloning of the cDNA encoding human brain trypsinogen and characterization of its
      product.
AB  - We designed degenerated oligodeoxyribonucleotide primers derived from amino acid
      (aa) sequences of the highly conserved active sites of mammalian serine proteases
      (SPs). These primers were used to selectively amplify, in polymerase chain
      reactions (PCRs), cDNA fragments coding for a SP. We used poly(A)+RNA from human
      brain to obtain cDNA fragments and amplified one cDNA encoding a novel SP. The
      full-length nucleotide (nt) sequence was identified by PCR and screening a
      genomic library in order to obtain the 5'-region. The deduced as sequence shows a
      high degree of homology to trypsinogens, except for the first exon. In addition
      to this brain-specific trypsinogen, there exists a variant of the cDNA in
      pancreas, differing only in the nt sequence of the first exon. An active form of
      the trypsin was synthesized in vitro and purified by affinity chromatography
      using soybean trypsin inhibitor (STI) agarose to demonstrate the trypsin-specific
      interaction with a naturally occurring inhibitor of trypsins.

PMID- 8294001
TI  - Cloning, expression and characterisation of the cDNA encoding human hepatic
      squalene synthase, and its relationship to phytoene synthase.
AB  - The reaction catalysed by squalene synthase (SQS) shows many similarities to that
      performed by another polyisoprene synthase, phytoene synthase (PhS). By
      identifying sequences conserved between yeast SQS (ySQS) and PhS, we have cloned
      a 2-kb cDNA (hSQS) encoding human SQS, a protein of 417 amino acids with a
      predicted M(r) of 48,041, which has only limited homology to ySQS. When expressed
      in E. coli, the hSQS cDNA directed the production of active enzyme. Two hSQS mRNA
      species of 2.0 and 1.55 kb have been identified which differ in their 3'
      untranslated sequences. The two mRNAs are present in roughly equal amounts in
      heart, placenta, lung, liver, kidney and pancreas, but the 2-kb mRNA predominates
      in brain and skeletal muscle. In HepG2 cells, both mRNAs are induced 2-4-fold by
      the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, lovastatin. In
      contrast, Northern blot analysis of rat tissues reveals only a 2.0-kb mRNA, which
      is considerably up-regulated in vivo by lovastatin.

PMID- 8294002
TI  - An expression-packaging-processing vector which selects and maintains 7-kb DNA
      inserts in the blue T4 phage genome.
AB  - We have developed an efficient positive-selection vector to insert foreign DNA
      segments fused to the T4 ipIII gene (encoding internal protein IPIII) into the
      bacteriophage T4 genome. By using partial deletions of the T4 e gene, which
      encodes phage lysozyme, lysozyme activity required for plaque formation is used
      to select plasmid integrants which restore the e gene. In this work, we
      demonstrate that DNA inserts more than 7.0 kb in length can be incorporated into
      a T4 genome lacking the alt gene. In addition, the recombinant T4 not only
      contains a fusion gene driven by the T4 ipIII promoters, but also packages the
      fusion protein into the T4 capsid due to targeting by the IPIII portion. This
      expression-packaging-processing system shows that active IPIII::beta Gal fusion
      reporter protein is produced and packaged during phage infection.

PMID- 8294003
TI  - A versatile and highly repressible Escherichia coli expression system based on
      invertible promoters: expression of a gene encoding a toxic product.
AB  - A very flexible and tightly regulatable expression system has been constructed.
      It uses the principle of invertible promoters [Podhajska et al., Gene 40 (1985)
      163-168]. Here, we describe the construction of a plasmid that provides the
      integrase, which causes promoter inversion in a tightly regulated fashion, as
      well as modified plasmids carrying the invertible module. The way the integrase
      is provided on a separate plasmid closely mimicks expression of the integrase
      from a lambda lysogen. Thus, the flexibility of the original system is
      considerably extended by making it strain-independent without compromising the
      tight regulation. We present the expression of a single-chain T-cell receptor
      fragment as an example of application, in order to illustrate the properties of
      this expression system.

PMID- 8294004
TI  - Plasmid pBRINT: a vector for chromosomal insertion of cloned DNA.
AB  - Plasmid pBRINT is a pBR322 derivative [Bolivar et al., Gene 2 (1977) 95-113;
      Balbas et al., Gene 50 (1986) 3-40] that allows the insertion and replacement of
      DNA sequences into the Escherichia coli chromosome by homologous recombination.
      This method uses the inability of E. coli strain ATCC47002 (JC7623) to replicate
      covalently closed circular (ccc) pBR322-derived plasmids, and the convenience of
      XGal+IPTG screening for recombinants. The vector also contains suitable selection
      markers (Ap and Cm), as well as a multiple cloning site (MCS) derived from the
      pUC vectors [Yanisch-Perron et al., Gene 33 (1985) 103-119] to facilitate
      cloning. A simple PCR scheme was developed to scan for DNA insertions into the
      bacterial chromosome. Once introduced into the chromosome, the inserted DNA
      sequences can be transferred to other strains by bacteriophage P1-mediated
      transduction.

PMID- 8294005
TI  - Tropist3: a cosmid vector for simplified mapping of both G+C-rich and A+T-rich
      genomic DNA.
AB  - We have constructed a cosmid vector, Tropist3, based on the lambda origin double
      cos-site vector Lawrist4, which is designed for efficient cloning and mapping of
      genomic DNA. Tropist3 contains two cloning sites in addition to the HindIII and
      BamHI sites present in Lawrist4; a SalI site allows cloning of Sau3AI partial
      digests following partial filling-in of the ends, and a PmlI site is suitable for
      blunt-end cloning. Both these strategies reduce the chance of co-cloning two
      inserts. Tropist3 also contains NotI, PacI, SacII and KpnI sites flanking the
      cloning region; these allow most inserts to be excised cleanly and mapped by
      partial digestion followed by hybridization with short vector sequences which lie
      adjacent to the cloning sites. This will also be useful for recloning inserts
      into different vectors, or for cosmid sequencing projects.

PMID- 8294006
TI  - A novel rapid hybridization technique: paper chromatography hybridization assay
      (PACHA).
AB  - A new DNA hybridization technique, based on chromatographic migration of DNA on a
      nitrocellulose strip passing through an immobilized probe area, is described. The
      new paper chromatography hybridization assay (PACHA) is faster and simpler to use
      than the conventional dot hybridization assay. In this assay, an aliquot of
      biotinylated, PCR-amplified target DNA is applied to one end of a nitrocellulose
      strip. The DNA migrates to the opposite end of the strip by capillary forces and
      hybridizes to a specific DNA probe immobilized in a reaction zone (RZ), located
      in the middle of the strip. Unhybridized DNA migrates away from the RZ. The
      biotinylated hybrid is visualized by a color reaction employing a streptavidin
      alkaline phosphatase (SA-AP) conjugate and a specific chromogenic substrate. The
      new PACHA technique allows for detection of as little as 1-5 pg of specific human
      papilloma virus 16 (HPV16) DNA in 25 min of hybridization. In this system, the
      hybridization efficiency is controlled by the flow velocity of the hybridization
      solution (HS) and by the volume of the amplified labeled DNA migrating across the
      immobilized probe. Glycerol (30%) or polyvinyl pyrrolidone (PVP) (1%) reduces the
      flow rate by a factor of 2.5-3 and increases the sensitivity of the assay by a
      factor of 5.2 for glycerol and 2.6 for PVP. This novel method ensures efficient
      hybridization to multiple probes and appears to be superior to currently
      available solid-phase hybridization techniques.

PMID- 8294007
TI  - The deduced amino-acid sequence of the cloned cpxR gene suggests the protein is
      the cognate regulator for the membrane sensor, CpxA, in a two-component signal
      transduction system of Escherichia coli.
AB  - The cpxA gene of Escherichia coli K-12 encodes a membrane-associated sensor
      element of a two-component signal transduction system in bacteria. The cognate
      regulator element, however, has not yet been definitively identified. A 2.1-kb
      segment upstream from cpxA was amplified by polymerase chain reaction, cloned and
      sequenced. An open reading frame encoding 232 amino acids was found. It showed
      high homology to the regulator elements of two-component transduction systems.
      The newly identified gene, designated as cpxR, may encode the cognate protein
      receiving signals from CpxA.

PMID- 8294008
TI  - Controlled high-level expression of the lon gene of Escherichia coli allows
      overproduction of Lon protease.
AB  - Lon protease from Escherichia coli is an ATP-dependent protease which plays
      important roles in regulating the levels of specific proteins and in eliminating
      abnormal proteins. A major problem of working with Lon protease, the inability to
      substantially overproduce the enzyme, has been overcome by placing the lon gene
      under the control of an inducible trp promoter within a copy-number-controllable
      plasmid. Induction resulted in higher levels of production of the protease
      (approximately 100 micrograms/ml of cell culture) than were previously possible.
      The enzyme has been purified to apparent homogeneity and shown to possess the
      characteristic ATP-dependent proteolytic activity. Sequence verification during
      DNA manipulations revealed differences from two previously published sequences
      for the lon gene.

PMID- 8294009
TI  - Construction and expression of a synthetic streptavidin-encoding gene in
      Escherichia coli.
AB  - A synthetic gene encoding 'core' streptavidin (SAV) [amino acid (aa) residues 13
      140 of Streptomyces avidinii SAV] has been efficiently expressed in Escherichia
      coli from the IPTG-inducible lac promoter of plasmid pET3a. In this system,
      expression levels are nearly tenfold greater for the synthetic gene than for the
      corresponding native gene. The synthetic gene was constructed from overlapping
      oligodeoxyribonucleotides whose sequences were optimized to incorporate codons
      preferred by highly expressed E. coli genes. Biochemical characterizations by gel
      methods, aa analysis, N-terminal sequencing, and size exclusion chromatography
      show that the synthetic gene product purified by affinity chromatography
      possesses the properties expected for core SAV.

PMID- 8294010
TI  - Cloning and sequence of an alkaline serine protease-encoding gene from the marine
      bacterium Alteromonas sp. strain O-7.
AB  - The gene (aprII) encoding alkaline serine protease (AprII; subtilase) from
      Alteromonas sp. strain O-7 was cloned in plasmid pUC19 and transformed into
      Escherichia coli JM109. The nucleotide (nt) sequence of aprII has been
      determined. A single open reading frame (ORF) encoded a protein consisting of 621
      amino acids (aa) with a M(r) of 63,958. The results of aa sequence analysis
      indicated that AprII is produced as a large precursor consisting of four domains:
      the signal sequence, the N-terminal pro-region (AprII-N), the mature AprII (AprII
      M) and the C-terminal pro-region (AprII-C). The aa sequence of AprII-M shows high
      sequence homology with those of class-II subtilases. Two conserved sequences were
      found in AprII-N which might play a critical role in the maintenance of chaperone
      like activity. Repeated aa sequences were observed in AprII-C (AprII-C1 and AprII
      C2). The aa sequences of AprII-C1 and AprII-C2 show high sequence homology with
      those of the C-terminal pro-region of the other known proteases.

PMID- 8294011
TI  - A counterselectable pACYC184-based lacZ alpha-complementing plasmid vector with
      novel multiple cloning sites; construction of chromosomal deletions in Klebsiella
      pneumoniae.
AB  - We have constructed a series of small, chloramphenicol-resistance-encoding, lacZ
      alpha-complementing vectors with novel multiple cloning sites, based on the
      pACYC184 replicon. The sacB gene of Bacillus subtilis, which is lethal to Gram-
      organisms in the presence of sucrose, was cloned into one of these, giving the
      counterselectable vector pSG335. This was used to substitute a streptomycin
      resistance-encoding cassette for the ntrBC genes in the Klebsiella pneumoniae
      chromosome.

PMID- 8294012
TI  - A mutagenesis system utilizing a Tn1722 derivative containing an Escherichia coli
      specific vector plasmid: application to Pseudomonas species.
AB  - A novel transposon (Tn) mutagenesis system for Gram- non-enteric bacteria was
      developed which allowed rapid and one-step cloning of the mutated region in
      Escherichia coli. The Tn constructed was Tn1722-299Km, a Tn1722 derivative
      containing a KmR gene and the entire sequence of an E. coli-specific plasmid,
      pACYC184. The hybrid plasmid consisting of Tn1722-299Km and the transfer genes of
      plasmid R388 was conjugally transferred from E. coli to Pseudomonas putida or P.
      aeruginosa, and selection of the transconjugants expressing the Tn-specified
      resistance genes led to isolation of insertion mutants of the recipient strain.
      The presence of the pACYC184 replicon in the Tn greatly facilitated rapid and
      easy cloning of the mutated region in E. coli through (i) mini-scale preparation
      of the genomic DNA from the Tn-inserted mutant, (ii) digestion of the DNA with an
      appropriate restriction endonuclease, (iii) self-ligation, and (iv)
      transformation of E. coli to recover the plasmid carrying the Tn-specified
      resistance marker. This procedure was successfully adapted to clone the Tn
      inserted trpBA region of P. putida. Such a cloned region was further employed to
      isolate the wild-type allele of the trpBA region without construction of a
      genomic library.

PMID- 8294013
TI  - Construction of chromosomal recA mutants of Pseudomonas putida PpG2.
AB  - The recA gene of Pseudomonas putida PpG2 was cloned by complementation of the
      recA mutations of Escherichia coli strains DH5 alpha and HB101. The nucleotide
      sequence of the DNA fragment was determined and shown to contain recA and a
      downstream partial open reading frame. Two mutants of P. putida PpG2, strains
      JS387 and JS388, were constructed by insertional inactivation of recA with a
      tetracycline-resistance gene in both orientations. Both mutants acquired
      sensitivity to methyl methanesulfonate (MMS) and both failed to undergo
      homologous recombination. While the recA mutation of P. putida JS388 was
      complemented in trans by recA of P. putida, the JS387 mutant was difficult to
      transform and transformants exhibited varying degrees of sensitivity to MMS.
      Therefore, P. putida JS388 can be used as a carrier of recombinant plasmids, but
      JS387 is not a suitable host for this purpose.

PMID- 8294014
TI  - Sequence of the alg8 and alg44 genes involved in the synthesis of alginate by
      Pseudomonas aeruginosa.
AB  - The alg8 and alg44 genes, which are required for alginate biosynthesis by
      Pseudomonas aeruginosa, are located in the alginate biosynthetic gene cluster
      between the algD and algE genes. The nucleotide sequence of these two genes is
      presented. Although the functions of the Alg8 and Alg44 proteins are not known,
      we believe that they may be involved in the polymerization of mannuronic acid
      residues to form alginate.

PMID- 8294015
TI  - Phosphotransferase system of Streptococcus salivarius: characterization of the
      ptsH gene and its product.
AB  - The Streptococcus salivarius ptsH gene encoding histidine-containing
      phosphocarrier protein (HPr) of the phosphotransferase system (PTS) has been
      cloned, sequenced, and found to be part of a ptsH, ptsI operon. Upstream from
      ptsH, putative -35 and -10 boxes and a Shine-Dalgarno sequence highly similar to
      the Escherichia coli consensus regulatory elements were identified. A second
      promoter, located in the ptsH coding sequence was also observed and is sufficient
      for the expression of the S. salivarius ptsI gene, encoding enzyme I of the PTS
      in E. coli [Gagnon et al., Gene 121 (1992) 71-78]. The amino acid sequence of S.
      salivarius HPr, inferred from the ptsH sequence, shared identity varying between
      37 and 76% with known HPr from other bacteria. Moreover, the S. salivarius HPr
      shared 78% identity with an HPr-like protein of Aspergillus fumigatus, a
      eukaroytic mold that does not possess a functional PTS. Expression analysis of S.
      salivarius HPr in E. coli demonstrated that (i) S. salivarius ptsH is expressed
      in E. coli under the control of its own promoter, (ii) S. salivarius HPr
      synthesized by E. coli is completely processed by methionine aminopeptidase, and
      (iii) S. salivarius HPr is phosphorylated in vivo by E. coli enzyme I. It was
      also observed that, in E. coli, the copy number of pUC18 bearing S. salivarius
      ptsH was reduced more than 25-fold, as compared to pUC18 without an insertion.

PMID- 8294016
TI  - Cloning of the YenI restriction endonuclease and methyltransferase from Yersinia
      enterocolitica serotype O8 and construction of a transformable R-M+ mutant.
AB  - Two different clonal groups of pathogenic Yersinia enterocolitica strains,
      American and non-American, have been recognized. These are distinguished by a
      number of criteria, including their virulence in a murine model of infection.
      However, genetic analysis of virulence in American strains has been hampered due
      to the severe restriction of transformed or electroporated DNA. Thus, we cloned
      the yenIMR locus from the American serotype strain 8081c, which encodes YenI, an
      isoschizomer of PstI. This clone encodes both the restriction endonuclease and
      methyltransferase. The location of the genes on the clone was determined and this
      information was used to construct a small deletion (400 bp) that results in an R
      M+ phenotype. This mutation was recombined onto the Y. enterocolitica chromosome
      to give an R-M+ mutant which showed at least a 1000-fold increase in
      electroporation frequency compared to the wild-type strain. Southern analysis
      using a probe derived from yenIMR indicated that American serotype strains have
      this locus whereas non-American serotype strains do not.

PMID- 8294017
TI  - Mapping of the Bacillus subtilis cspB gene and cloning of its homologs in
      thermophilic, mesophilic and psychrotrophic bacilli.
AB  - The Bacillus subtilis cold shock (CS)-inducible gene, cspB, encoding the nucleic
      acid-binding, major CS protein CspB, is located at about 80 degrees on the B.
      subtilis genetic map. Using this cspB as a probe, the CspB-encoding genes from
      two thermophilic bacilli were cloned and characterized. The nucleotide (nt)
      sequences of the B. caldolyticus and B. stearothermophilus cspB coding regions
      are 78 and 76% identical to the B. subtilis cspB and the deduced amino acid (aa)
      sequences revealed 84 and 82% identity, respectively. The cspB genes of the
      mesophilic B. globigii and the some what psychrotrophic B. globisporus, were
      amplified by PCR using mixed degenerate oligodeoxyribonts based on the 5' and 3'
      ends of B. subtilis cspB. The nt sequence comparisons of the resulting cloned PCR
      fragments revealed 98 to 99% identity to cspB of B. subtilis and 97% aa identity
      to the CspB protein. The high conservation of CspB within the genus Bacillus and
      the presence of a related nucleic acid-binding domain within several eukaryotic
      transcription factors implies an important common biological function that seems
      to be highly conserved from bacteria to man.

PMID- 8294018
TI  - The Haemophilus influenzae dnaG sequence and conserved bacterial primase motifs.
AB  - The dnaG gene encodes primase which synthesizes the primer RNA essential for
      Escherichia coli chromosomal DNA replication. The nucleotide sequence was
      determined for the Haemophilus influenzae dnaG gene and used in the molecular
      evolutionary analysis of primases from six bacterial species. The predicted amino
      acid (aa) sequence of H. influenzae DnaG contains 593 residues and shares 56%
      identity with E. coli DnaG. The N-terminal 60% of six aligned bacterial primases
      contains all 71 absolutely conserved aa residues and several conserved motifs.
      All six bacterial primases which were sequenced contained a conserved
      CPFHXEKTPSF(T/S/A)VXXXKQX(F/Y)HCFGC zinc finger (zf) in the N terminus. A basic
      region in the N-terminal half of the primases contains a conserved motif,
      G(R/K)X(V/I/L)X(F/Y) (G/S/A)(G/S/A)RX(V/I/L)XXXXP, termed 'RNAP-basic', which is
      shared only with RNA polymerase (RNAP) large subunits. This conserved sequence
      represents the first motif common and specific to primases and RNAP subunits. The
      consensus sequence, PKYLNSPET, lies adjacent to this basic region in bacterial
      primases and may represent a signature sequence for bacterial DnaG. The C
      terminal regions of these primases do not appear to share primary sequence
      similarities. These findings support our hypothesis that the primase active site
      of DnaG is located in the N-terminal 60% of the enzyme.

PMID- 8294019
TI  - A PCR method for the sequence analysis of the gyrA, polA and rnhA gene segments
      from mycobacteria.
AB  - Internal segments of the gyrA and polA genes involved in DNA replication of
      Mycobacterium tuberculosis and rnhA of M. smegmatis, have been amplified by the
      polymerase chain reaction (PCR) using degenerate oligodeoxyribonucleotide primers
      based on conserved sequences. The deduced amino acid sequences were 54-66%
      homologous to the corresponding segments of their Escherichia coli counterparts.
      This method provides a useful means of cloning genes encoding DNA replication
      enzymes of mycobacteria.

PMID- 8294020
TI  - Derivation of the complete msp4 gene sequence of Anaplasma marginale without
      cloning.
AB  - The gene encoding MSP4, a 31-kDa surface protein of the rickettsia Anaplasma
      marginale, was completely sequenced without prior cloning of the gene. Degenerate
      oligodeoxyribonucleotides (oligos) corresponding to the N-terminal amino-acid
      sequence of MSP4 were used as primers in the polymerase chain reaction (PCR) to
      amplify a 65-bp fragment of which the central 32 bp was nondegenerate. The 32-bp
      probe was hybridized to restriction enzyme-digested, genomic A. marginale DNA in
      Southern blots, and the hybridizing fragment was size selected from agarose gels
      and ligated into the Bluescript II SK (+/-) plasmid. The ligation reaction
      mixture was used as a template for PCR, amplified from the 32-bp oligo or its
      inverse complement to plasmid sequences. The PCR products were sequenced to
      obtain the entire msp4 gene and surrounding regions. This method of sequencing a
      gene without previously obtaining a clone for that gene could be beneficial in
      situations where conventional cloning and screening strategies are inefficient or
      ineffective.

PMID- 8294021
TI  - The leu-1 gene of Neurospora crassa: nucleotide and deduced amino acid sequence
      comparisons.
AB  - The Neurospora crassa leu-1 gene encodes beta-isopropylmalate dehydrogenase
      (IPMDH; EC 1.1.1.85), an enzyme in the leucine biosynthetic pathway. We
      determined the nucleotide sequence of the entire leu-1 gene and of four
      independent cDNA clones. By comparing the genomic and cDNA sequences, four
      introns were identified in the 5' portion of the gene and a single open reading
      frame was established. One of the introns is located within the 5'-noncoding
      region of the transcript. The deduced amino acid sequence encoded by leu-1 was
      aligned with that of the homologous yeast enzyme and extensive sequence identity
      was uncovered. The lesion present in a conventional leu-1 mutant was identified
      as the insertion of a single base pair.

PMID- 8294022
TI  - Gene replacement in the lignin-degrading basidiomycete Phanerochaete
      chrysosporium.
AB  - The ability to carry out gene replacements and gene targeting in the lignin
      degrading basidiomycete fungus, Phanerochaete chrysosporium, would facilitate
      studies on the roles and regulation of various components of its lignindegrading
      system. A plasmid consisting of the P. chrysosporium ura3 gene (encoding
      orotidylate decarboxylase) interrupted with the Schizophyllum commune ade2 gene
      (encoding an adenine biosynthetic enzyme) was used to transform the P.
      chrysosporium ade2 strain to adenine prototrophy with selection on 5-fluoroorotic
      acid for inactivation of the ura3 gene. Stable Ade+Ura- strains were obtained at
      a frequency of approximately one transformant per microgram of DNA. In all of the
      Ade+Ura- transformants examined by Southern analysis, the chromosomal ura3 locus
      had been replaced by the plasmid insert.

PMID- 8294023
TI  - Isolation of Trichoderma reesei genes highly expressed on glucose-containing
      media: characterization of the tef1 gene encoding translation elongation factor 1
      alpha.
AB  - Genes that are highly expressed on glucose-containing media were isolated from
      the filamentous fungus, Trichoderma reesei. A cDNA bank was prepared from glucose
      grown fungus, the bank was screened with the same cDNA as a probe, and clones
      giving the strongest signal were isolated. This resulted in the isolation of
      previously uncharacterized genes. Five of the genes, representing the most
      abundant transcripts, corresponded to 1-3% of the total mRNA population and were
      clearly more highly expressed than the phosphoglycerate kinase-encoding gene
      (pgk1) of T. reesei. Based on sequence homology, one of the genes was identified
      as tef1, encoding translation elongation factor 1 alpha (TEF). The T. reesei TEF
      is most related to the Mucor racemosus TEF3, showing an overall amino acid
      similarity of 85%. Interestingly, an exon of only 2 bp seems to be present in T.
      reesei tef1, comprising the first 2 bp of the Gly15 codon.

PMID- 8294024
TI  - The macronuclear gamma-tubulin-encoding gene of Euplotes octocarinatus contains
      two introns and an in-frame TGA.
AB  - The gamma-tubulin (gamma-Tub)-encoding gene (gamma-tub) of Euplotes octocarinatus
      was amplified from macronuclear DNA with the help of the polymerase chain
      reaction (PCR) and sequenced. The polypeptide deduced from the gene consists of
      462 amino acids (aa). It shares 61% aa identity with the Aspergillus nidulans
      gamma-Tub. The gene contains an in-frame TGA codon and two small pre-mRNA introns
      (36 and 26 bp). We suggest that the TGA, like TGA codons in the pheromone
      encoding genes of E. octocarinatus, codes for a cysteine. This suggestion is
      supported by the finding that in the gamma-Tub of other organisms, a cysteine is
      located at this position. Sequencing the mRNA revealed that the introns are
      absent from the gamma-tub transcripts. The second intron constitutes the shortest
      one reported so far. We have also sequenced the 5'- and 3'-flanking regions of
      the gene up to the telomeres and report here the entire sequence of the
      macronuclear DNA molecule carrying gamma-tub.

PMID- 8294025
TI  - The gene encoding mouse lymphocyte antigen Ly-49: structural analysis and the 5'
      flanking sequence.
AB  - Genomic clones encoding the mouse cell-surface antigen, Ly-49, were isolated, and
      the gene organization was analyzed. The gene spanned approximately 19 kb, and
      contained seven exons and six introns. The lengths of introns ranged from 1.3 to
      8 kb. A 1067-bp sequence in the 5'-flanking region was determined. Primer
      extension analysis and S1 nuclease mapping revealed a cap site at 158 bp upstream
      from the ATG coding the N-terminal Met of Ly-49. The 5'-flanking sequence
      contained a possible promoter sequence, a potential binding site for the T cell
      specific transcription factor (TCF-1 alpha/LEF-1), and three sites for the basic
      helix-loop-helix-binding basic proteins (bHLH). However, no CAAT box-like
      sequence was present. These results provide important clues for understanding the
      mechanism of gene expression of lymphocyte antigens.

PMID- 8294026
TI  - Cloning and sequencing of a novel rat cytochrome P450 2B-encoding gene.
AB  - A novel rat P450 2B gene encoding cytochrome P450 2B15 was cloned and sequenced.
      The gene is separated into nine exons by eight introns. This gene structure is
      very similar to those of P450 2B1 and 2B2, except that the coding sequences of
      the gene are longer in the first and ninth exons than those of the P450 2B1 and
      2B2 genes.

PMID- 8294027
TI  - Overproduction of the toxic protein, bovine pancreatic DNaseI, in Escherichia
      coli using a tightly controlled T7-promoter-based vector.
AB  - A synthetic gene coding for bovine pancreatic DNaseI has been cloned under the
      control of a T7 promoter present on the plasmid pET11. This construct yields a
      stable Escherichia coli transformant only when transcription from this promoter
      is tightly controlled. Production of recombinant DNaseI (reDNaseI) is achieved by
      infection of the cells with a mutant lambda phage, CE6, which carries the gene
      encoding T7 RNA polymerase. Induced bacterial cultures yield in excess of 2 mg
      per litre of reDNaseI after purification.

PMID- 8294028
TI  - Possible implications of Sp1-induced bending of DNA on synergistic activation of
      transcription.
AB  - We examined DNA bending using an electrophoretic mobility shift assay to
      determine whether Sp1 induces structural changes in DNA. The results indicated
      that Sp1 bends DNA upon binding to its recognition sequence. We discuss the
      possibility that DNA bending is involved in synergistic activation of
      transcription.

PMID- 8294029
TI  - Genomic characterization of the human DNA excision repair-controlling gene XPAC.
AB  - We have characterized the human DNA excision repair gene, XPAC (xeroderma
      pigmentosum group A complementing). This gene of approximately 25 kb consists of
      six exons. The 5'-flanking region of the gene has a CAAT box, but no TATA box.
      The region upstream from the coding sequence of exon 1 is G + C rich (73%), and
      has a GC box. Transcriptional mapping analysis suggested that there is one major
      transcription start point (tsp). The presence of two polyadenylation signals
      suggests that the two XPAC mRNAs with different 3' untranslated regions in normal
      human cells are due to alternative polyadenylations. The promoter activity,
      measured by transient expression of the cat gene with the 5' flanking regions,
      indicated the presence of a functional promoter.

PMID- 8294030
TI  - The effect of the rat immunoglobulin heavy-chain 3' enhancer is position
      dependent.
AB  - We tested the effect of the immunoglobulin (Ig) heavy- and kappa-chain 3'
      enhancers on the expression of Ig genes in B-cells. Inclusion of the heavy-chain
      3' enhancer in addition to the mu intron enhancer increased the expression rate
      up to sixfold, but this effect was strongly position dependent, in that it was
      only observed when the element was located downstream from the constant exons.
      Furthermore, the stimulatory effect could be augmented by increasing the distance
      between the constant gene segments and the 3' enhancer. When the 3' enhancer was
      located upstream from the variable gene promoter, the transcription was
      dramatically suppressed. Thus, the heavy-chain 3' enhancer does not fit into the
      usual definition of an enhancer element. The implications for the production of
      recombinant antibodies are discussed.

PMID- 8294031
TI  - The sequence of the Haemophilus influenzae mutB gene indicates it encodes a DNA
      helicase II-like protein.
AB  - A 6.2-kb Haemophilus influenzae genomic DNA fragment which partially complemented
      both the mutator and ultraviolet light sensitive (UVs) phenotypes of the H.
      influenzae mutB1 mutant was isolated. This fragment was also able to complement
      the UVs phenotype of Escherichia coli uvrD mutant hosts. The uvrD+ gene
      complemented the mutator phenotype of mutB1 hosts. The nucleotide (nt) sequence
      of the 6.2-kb fragment revealed an open reading frame (ORF) of 2184 bp. This ORF
      shows similarity at both the nt and amino acid (aa) levels with the uvrD gene of
      E. coli. Comparison of the sequences revealed eight regions of aa conservation in
      addition to seven previously identified helicase superfamily domains. The nt
      sequence 5' to the mutB ORF contains several potential regulatory motifs,
      including a LexA-binding site. Based upon these observations, we are confident
      that the mutB gene of H. influenzae encodes an ATP-dependent DNA helicase-like
      activity.

PMID- 8294032
TI  - A human gene that shows identity with the gene encoding the angiotensin receptor
      is located on chromosome 11.
AB  - We report the cloning of a gene, intronless in its coding region, which we have
      named APJ. This gene was cloned using the polymerase chain reaction (PCR), with a
      set of primers designed on the basis of the conservation that members of G
      protein-coupled receptors (GPCR) have in their transmembrane (TM) regions. The
      putative receptor protein, APJ, shares closest identity to the angiotensin
      receptor (AT1) ranging from 40 to 50% in the hydrophobic TM regions of these
      receptors. The transcripts for this gene were detected in many regions of the
      brain. PCR analysis of somatic cell lines found APJ-related sequences to be only
      present on chromosome 11, and high-resolution mapping by fluorescence in situ
      hybridization (FISH) sublocalized APJ on band q12.

PMID- 8294033
TI  - A novel transcript from a pseudogene for human glucocerebrosidase in non-Gaucher
      disease cells.
AB  - Human glucocerebrosidase (GC)-encoding cDNA clones were isolated from a
      promyelocytic HL-60 cDNA library and analyzed. A novel cDNA clone was found to
      originate from a gene referred to as a GC pseudogene. Using the polymerase chain
      reaction (PCR) with primers specific for the GC pseudogene, we found that all the
      human cell lines examined, HL-60, K-562, WI-38, HepG2 and HeLa, expressed a
      pseudogene transcript. In vitro translation of RNA synthesized by transcription
      of the pseudogene cDNA produced a polypeptide of approximately 30 kDa.

PMID- 8294034
TI  - New vectors for direct cloning of PCR products.
AB  - We describe the construction of two new vectors for direct cloning of polymerase
      chain reaction (PCR) products. This was done by inserting a synthetic DNA
      fragment containing two adjacent XcmI sites between the Asp718 and BamHI sites of
      the M13mp18 and M13mp19 phages. Cleavage of these M13 derivatives with XcmI will
      result in a linearized vector with a single thymidine nucleotide at the 3' ends.
      Thus, these vectors would be very useful for direct cloning of PCR-generated
      products with high efficiency.

PMID- 8294035
TI  - LlaAI and LlaBI, two type-II restriction endonucleases from Lactococcus lactis
      subsp. cremoris W9 and W56 recognizing, respectively, 5'-/GATC-3' and 5'-C/TRYAG
      3'.
AB  - Two type-II restriction endonucleases have been purified from Lactococcus lactis
      subsp. cremoris W9 and W56, the strains isolated from a mixed Cheddar starter.
      Their characterization showed that LlaAI was an isoschizomer of MboI from
      Morexella bovis with the cleaving sequence, 5'/GATC-3', being sensitive to
      methylation of the adenine residue; LlaBI was an isoschizomer to SfcI from
      Streptococcus faceium with the cleaving sequence, 5'-C/TRYAG-3'. Both LlaAI and
      LlaBI restriction-modification (R-M) systems are encoded by the plasmids,
      respectively, pFW094 and pJW563, protecting the harboring strain against phage
      attack.

PMID- 8294036
TI  - Sequence of the gene encoding ribosomal protein L11 from Thermus thermophilus
      HB8.
AB  - The complete nucleotide sequence of the gene encoding ribosomal protein L11 from
      the extreme thermophilic eubacterium, Thermus thermophilus HB8, was determined.
      L11 amino acid (aa) sequences from mesophilic and halophilic organisms, as well
      as from another thermophiles, were compared with the T. thermophilus L11 aa
      sequence.

PMID- 8294037
TI  - Isolation and characterization of a full-length trypsin-encoding cDNA clone from
      the Lepidopteran insect, Choristoneura fumiferana.
AB  - The protease-encoding genes of Lepidopteran insects are of interest because they
      are adapted to functioning at very high pH optima, in the range of pH 10-12.
      Here, we report the isolation and sequence characterization of a trypsin-encoding
      cDNA clone from the spruce budworm, Choristoneura fumiferana.

PMID- 8294038
TI  - Characterization of the transcripts encoding two isoforms of human microtubule
      associated protein-2 (MAP-2).
AB  - Through the isolation of a series of overlapping clones from human fetal and
      adult cDNA libraries, we have generated the complete cDNA sequences encoding
      human high- and low-molecular-weight microtubule-associated protein-2 (MAP-2)
      which have strong sequence homology with rodent MAP-2.

PMID- 8294039
TI  - Cloning and sequencing of the gene encoding thermostable elongation factor 2 in
      Sulfolobus solfataricus.
AB  - The gene (aEF-2) coding for the translation elongation factor 2 (aEF-2) in the
      thermoacidophilic archaebacterium, Sulfolobus solfataricus, has been cloned and
      sequenced. The deduced primary structure of aEF-2 is composed of 735 amino acids
      (aa), excluding the Met start residue. There are no Cys residues and the
      calculated M(r) is 81,699. In the coding region of aEF-2, the high A + T content
      greatly influences the codon usage. From the alignment of the primary structure
      of aEF-2 with that of the analogous factors from the three kingdoms, aa
      identities were derived. The greatest identity (82%) was found with EF-2 from
      Sulfolobus acidocaldarius; lower values were observed with other archaebacterial
      EF-2 (45-47%), eukaryotic EF-2 (38-40%) and with the functional eubacterial
      analogue EF-G (28-31%). aEF-2 possesses the consensus sequences required for a
      GTP-binding protein and the four regions which are supposed to be involved in the
      functional regulation of EF-2/EF-G. These data should have phylogenetic
      implications.

PMID- 8294040
TI  - Genesis of eukaryotic transcriptional activator and repressor proteins by
      splitting a multidomain anabolic enzyme.
AB  - The genes necessary for the correctly regulated catabolism of quinate in
      Aspergillus nidulans and Neurospora crassa are controlled at the level of
      transcription by a DNA-binding activator protein and a repressor protein that
      directly interact with one another. The repressor protein is homologous
      throughout its length with the three C-terminal domains of a pentafunctional
      enzyme catalysing five consecutive steps in the related anabolic shikimate
      pathway. We now report that the activator protein is homologous to the two N
      terminal domains of the same pentafunctional enzyme and that this proposed
      structural similarity suggests a molecular mechanism by which the repressor
      recognises the activator protein. We believe that this is the first report of the
      genesis of a pair of interacting eukaryotic regulatory proteins by the splitting
      of a multidomain anabolic enzyme. The recruitment of preformed enzymatically
      active domains to a regulatory role may represent a general mechanism for the
      evolution of pathway-specific regulator proteins in dispensable pathways.

PMID- 8294041
TI  - Cloning and characterization of five novel Dictyostelium discoideum rab-related
      genes.
AB  - Low-M(r) GTPases belonging to the Ras superfamily are known to regulate a wide
      range of cellular processes including cell proliferation, actin cytoskeleton
      organization, and vesicular trafficking along the secretory and
      endosomal/lysosomal pathway. We are studying the regulation of lysosomal and
      endosomal vesicular trafficking in the simple eukaryote, Dictyostelium
      discoideum. Using an oligodeoxyribonucleotide (oligo) encoding one of the most
      highly conserved amino acid (aa) regions found in the low-M(r) GTPases (important
      in GTP binding), we have cloned 18 new cDNAs encoding proteins belonging to the
      Ras superfamily. In this report, we describe the characterization of five of
      these cDNAs coding for proteins belonging to the Ypt1/Sec4/Rab family; mammalian
      members of this family have been shown to function in the regulation of vesicular
      trafficking. Two of the cDNAs, rab1A and rab1B, code for proteins highly
      homologous to mammalian Rab1. An additional cDNA, rabA, codes for a protein that
      is only 60% identical to Rab1 at the aa sequence level and probably represents a
      new member of the rab gene family. Finally, two cDNAs, rabB and rabC, code for
      novel proteins belonging to the Rab gene family that are no greater than 50%
      identical in aa sequence to any previously described member. Southern blot
      analysis indicated that rab1A and and rab1B belong to a small Dictyostelium
      family of at least five related genes, while rabA belongs to a different and
      smaller family of related genes. In contrast, rabB and rabC appear to be
      represented by single genes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294042
TI  - Cloning and characterization of seven novel Dictyostelium discoideum rac-related
      genes belonging to the rho family of GTPases.
AB  - Cellular processes including proliferation, organization of the actin
      cytoskeleton, vesicular traffic and secretion of proteins comprising the
      lysosomal/endosomal system are regulated by low-molecular-weight GTP-binding
      proteins of the Ras superfamily. However, to date only three Dictyostelium
      discoideum ras-like genes and two ypt-1/sec4-like genes have been identified and
      characterized. We report here the identification (using an
      oligodeoxyribonucleotide probe) of seven additional cDNAs coding for members
      highly related to the Rac proteins (Ras-related-C3 botulinum toxin substrate)
      which belong to the Rho (Ras homologous) family of GTPases. Three of these rac
      related genes (rac1A, rac1B and rac1C) predict proteins with > 90% amino acid
      (aa) sequence identity with each other and > 80% identity to the human rac1 gene
      product, whereas the other members (racA, racB, racC and racD) predict proteins
      with 46-74% identity to the rac1 and rhoA gene products and to each other. The D.
      discoideum proteins were entirely conserved over the four regions known to be
      important for GTP binding and all contained the C-terminal CAAX aa motifs shared
      by other Rho proteins. Interestingly, the D. discoideum rac-related genes
      revealed unique patterns of expression during growth and development. For
      instance, the steady-state level of rac1 mRNA, encoded by three highly related
      genes, increased transiently during aggregation and then rapidly decreased. In
      contrast, the cellular abundance of mRNAs encoded by the other rac-like genes
      decreased at different rates and to different levels during development from the
      peak levels observed during growth. This suggests that the GTP-binding proteins
      encoded by these genes may play unique roles during the different stages of the
      D. discoideum life cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294043
TI  - Cloning and characterization of the gene encoding ATP-dependent phospho-enol
      pyruvate carboxykinase in Trypanosoma cruzi: comparison of primary and predicted
      secondary structure with host GTP-dependent enzyme.
AB  - The complete nucleotide (nt) sequence of the PEPCK gene encoding Trypanosoma
      cruzi phospho-enol-pyruvate carboxykinase (PEPCK; ATP dependent, EC 4.1.1.49) has
      been determined. The predicted primary sequence has 473 amino acids (aa) with a
      calculated molecular mass of 52.5 kDa. The ubiquitous spliced leader is present
      at nt position -60 from the AUG start codon in PEPCK mRNA; the coding region is
      followed by a long 3'-non-coding region of 777 nt. Northern and Southern blot
      analysis showed that the PEPCK mRNA is 2.7 kb long and that the PEPCK gene is
      polymorphic in T. cruzi, with more than one copy in the genome of the
      epimastigote form. Comparison of the available aa sequences of ATP(protozoa,
      yeast and bacteria)- and GTP(vertebrates, insects, helminths and fungi)-dependent
      PEPCKs showed that the former lack two characteristic, highly conserved regions
      present in the GTP-dependent enzymes: one is associated with the binding of PEP
      while the second is frequently labeled as 'catalytic' and contains a conserved
      Cys residue of unusual reactivity. On the other hand, two consensus sequences
      with conserved predicted secondary structure were identified in all PEPCKs,
      independent of their nt specificity; one of them is a divalent metal-binding site
      previously identified in pyruvate kinase by X-ray crystallographic studies.

PMID- 8294044
TI  - A negatively light-regulated gene from Arabidopsis thaliana encodes a protein
      showing high similarity to blue copper-binding proteins.
AB  - A negatively photo-regulated gene (bcb) has been isolated by means of
      differential hybridization of a genomic library of Arabidopsis thaliana. In
      mature plants, a 20-fold increase in the amount of steady-state bcb mRNA can be
      detected upon 48 h of dark adaption. The expression level of the gene is also
      dependent upon the developmental stage of the plant. The 21.5-kDa gene product
      (BCB) shows extensive similarity with blue Cu(2+)-binding proteins such as
      plastocyanin and stellacyanin. The protein abundance increases only twofold upon
      dark adaption, which implies the presence of post-transcriptional control. The
      isolation of a novel negatively photoregulated gene allows us to investigate the
      complex expression profile of genes responding to the absence of light.

PMID- 8294045
TI  - Transgenic plants that express genes including the 3' untranslated region of the
      turnip yellow mosaic virus (TYMV) genome are partially protected against TYMV
      infection.
AB  - In order to evaluate new possibilities for protecting plants against virus
      infection by interference with viral replication, two chimeric genes were
      constructed in which the (+) strand 3'-terminal 100 nucleotides (nt) of the
      noncoding region of the turnip yellow mosaic virus (TYMV) genome were placed
      downstream from the sense or antisense cat coding region. The two chimeric genes
      were then introduced into the genome of rapeseed (Brassica napus) using an
      Agrobacterium rhizogenes vector system. Plants expressing high levels of either
      chimeric gene showed partial protection against infection by TYMV RNA or virions.
      One interesting feature of the protection is that a proportion of the inoculated
      transgenic plants does not become infected. Protection was overcome when the
      inoculum concentration was increased. RNA complementary to the initial transcript
      was detected after infection.

PMID- 8294046
TI  - Neutrophil-catalysed dimerisation of tyrosyl peptides.
AB  - Evidence is given that tyrosyl-peptides are dimerised by polymorphonuclear
      leukocytes leading to a new family of compounds. The products formed are homo-
      and hetero-dimeric peptides with linkage between the tyrosyl residues. This
      corresponds to a dityrosine structure as determined by analytic and spectroscopic
      data.

PMID- 8294047
TI  - Direct evidence for nitric oxide stimulation of electrolyte secretion in the rat
      colon.
AB  - Nitric Oxide (NO) is synthesized in the intestinal tract and may serve as a
      physiological regulator of intestinal ion transport and/or a pathophysiologic
      mediator of secretory diarrhea associated with inflammatory mucosal diseases.
      Indirect approaches, employing inhibitors of nitric oxide synthase or compounds
      capable of donating NO in solution, have been used to demonstrate the effects on
      gastrointestinal muscle and the mucosa. To determine directly whether nitric
      oxide itself is capable of stimulating electrolyte secretion we mounted muscle
      stripped rat distal colon in Ussing chambers and monitored short-circuit current
      (Isc), as an indicator of effects on mucosal ion transport. Comparisons were made
      to sodium nitroprusside (SNP). NO and SNP stimulated concentration-dependent (0.1
      microM to 100 microM) increases in Isc, with NO being more potent than SNP. The
      EC50 for NO was approximately 8 microM compared to a value < 20 microM for SNP.
      The response to NO was immediate. In contrast, SNP required a mean lag-time of 41
      +/- 4 seconds, and a significantly longer time was required for SNP to reach its
      maximum effect. The response to both of these agonists was blocked by bumetanide,
      indicating that they were stimulating a chloride ion secretory response. The
      cyclooxygenase inhibitor piroxicam, the neurotoxin tetrodotoxin and the inhibitor
      of guanylate cyclase, methylene blue, all inhibited the response to both
      agonists. These studies demonstrate that NO itself can stimulate chloride
      secretion by the rat colonic mucosa through a prostaglandin-dependent, and
      partially neural mechanism that may involve guanylate cyclase.

PMID- 8294048
TI  - alpha-Phenyl-tert-butyl-nitrone (PBN) attenuates hydroxyl radical production
      during ischemia-reperfusion injury of rat brain: an EPR study.
AB  - Alpha-phenyl-tert-butyl-nitrone (PBN) a spin adduct forming agent is believed to
      have a protective action in ischemia-reperfusion injury of brain by forming
      adducts of oxygen free radicals including .OH radical. Electron paramagnetic
      resonance (EPR) has been used to both detect and monitor the time course of
      oxygen free radical formation in the in vivo rat cerebral cortex. Cortical cups
      were placed over both cerebral hemispheres of methoxyflurane anesthetized rats
      prepared for four vessel occlusion-evoked cerebral ischemia. Prior to the onset
      of sample collection, both cups were perfused with artificial cerebrospinal fluid
      (aCSF) containing the spin trap agent alpha-(4-pyridyl-1-oxide)-N-tert
      butylnitrone (POBN 100 mM) for 20 min. In addition 50 mg/kg BW of POBN was
      administered intraperitoneally (IP) 20 min prior to ischemia in order to improve
      our ability to detect free radical adducts. Cup fluid was subsequently replaced
      every 15 min during ischemia and every 10 min during reperfusion with fresh POBN
      containing CSF and the collected cortical superfusates were analyzed for radical
      adducts by EPR spectroscopy. After a basal 10 min collection, cerebral ischemia
      was induced for 15 or 30 min (confirmed by EEG flattening) followed by a 90 min
      reperfusion. .OH radical adducts (characterized by six line EPR spectra) were
      detected during ischemia and 90 min reperfusion. No adduct was detected in the
      basal sample or after 90 min of reperfusion. Similar results were obtained when
      diethylenetriaminepenta-acetic acid (100 microM; DETAPAC) a chelating agent was
      included in the artificial CSF. Systemic administration of PBN (100 mg/kg BW)
      produced a significant attenuation of radical adduct during reperfusion. A
      combination of systemic and topical PBN (100 mM) was required to suppress .OH
      radical adduct formation during ischemia as well as reperfusion. PBN free radical
      adducts were detected in EPR spectra of the lipid extracts of PBN treated rat
      brains subjected to ischemia/reperfusion. Thus this study suggests that PBN's
      protective action in cerebral ischemia/reperfusion injury is related to its
      ability to prevent a cascade of free radical generation by forming spin adducts.

PMID- 8294049
TI  - Analysis of lipoprotein diene formation in human serum exposed to copper.
AB  - The susceptibility of low density lipoprotein (LDL) to oxidative modification can
      be determined by analyzing the lag phase for initiation of diene formation in
      isolated LDL exposed to Cu2+. However, the applicability of this assay for
      clinical studies is limited by the requirement of a preparative
      ultracentrifugation of LDL and that the influence of water soluble antioxidants
      and other lipoproteins is not accounted for. The present paper describes a
      modification of this assay allowing determination of lag phase for lipoprotein
      diene formation in serum. The formation of dienes in serum exposed to Cu2+ begins
      following the consumption of serum alpha-tocopherol, correlates to the formation
      of thiobarbituric acid reactive substances (r = 0.987, n = 8), is inhibited by
      the addition of ascorbic acid and is absent in lipoprotein-deficient serum. It is
      also accompanied by an increased mobility of serum lipoproteins on agarose gel
      electrophoresis and with an ability of serum to displace isolated copper-oxidized
      LDL from binding sites mediating degradation in mouse peritoneal macrophages. The
      coefficient of variance of the analysis is below 3%. It is concluded that this
      technique allows analysis of lipoprotein oxidation susceptibility in serum
      samples and may prove to be useful in clinical analysis of the lipoprotein
      oxidation susceptibility.

PMID- 8294050
TI  - DNA-topoisomerase I and II: biologic features and their role in drug resistance.

PMID- 8294051
TI  - Effect of recombinant human erythropoietin on hematopoietic and non-hematopoietic
      malignant cell growth in vitro.
AB  - BACKGROUND: Several clinical studies have shown that recombinant human
      erythropoietin (rHuEpo) can ameliorate the anemia associated with hematologic
      malignancies and solid tumors. On the other hand, only a few studies have been
      performed to investigate whether rHuEpo can affect or modulate the growth of
      malignant cells. MATERIALS AND METHODS: We studied the effects of rHuEpo (0.5 to
      10 IU/mL) on clonogenic growth and cell kinetics in ten cell lines derived from
      both hematologic malignancies and solid tumors. Clonogenic assays were performed
      by plating 5 x 10(3) cells in agar, while the percentage of cells in S phase was
      assessed by DNA flow cytometry. RESULTS: rHuEpo did not affect either in vitro
      colony formation or S phase percentage in the human erythroid cell lines K-562
      and HEL expressing erythropoietin receptors (< 40 receptors per cell). No effect
      of rHuEpo was observed in the remaining hematopoietic cell lines or in five solid
      tumor cell lines. CONCLUSIONS: These findings indicate that rHuEpo, even at very
      high concentrations, does not affect either clonogenic growth or DNA synthesis in
      the cell lines tested. Available evidence suggests that rHuEpo can be safely
      employed in all malignancies except acute myeloid leukemia.

PMID- 8294052
TI  - In vitro chemosensitivity of chronic lymphocytic leukemia B-cells to multidrug
      regimen (CEOP) compounds using the MTT colorimetric assay.
AB  - BACKGROUND: Anthracycline-containing regimens have given controversial clinical
      results in CLL. Therefore, we explored the in vitro behavior of CLL B-cells after
      exposure to the compounds included in the most frequently used combination
      therapy regimen (CEOP). METHODS: A 4-day MTT colorimetric assay was used in vitro
      to test the effect of CEOP regimen drugs, either alone or in combination, on CLL
      B-cells. All drugs but mafosfamide, tested in place of cyclophosphamide, were
      used at concentrations corresponding to the in vivo dosage employed in the CEOP
      regimen. Chlorambucil was also studied since it represents the standard treatment
      for this disease. RESULTS: Epirubicin, prednisone and vincristine displayed a
      cytotoxic effect in 15, 13 and 4 out of 30 samples, respectively. Combinations of
      the same drugs showed a synergistic effect in 6 out of 13 assays. A cytotoxic
      effect of chlorambucil was detected in 2 out of 5 responders to the combination
      of CEOP regimen drugs, and in 3 out of 7 non responders. Mafosfamide induced a
      reduction in cell survival in 60-80% of the samples, depending on its
      concentration. CONCLUSIONS: The MTT assay is suitable for evaluating the in vitro
      chemosensitivity of CLL B-cells to multidrug regimen compounds. In the present
      study 40% of samples were resistant to CEOP regimen components in vitro. The
      possible role of MTT in predicting the clinical response to the CEOP regimen
      should still be established by prospective in vitro and in vivo studies.

PMID- 8294053
TI  - Impaired release of natural killer cytotoxic factor(s) by peripheral blood
      lymphocytes in patients with chronic LGL-proliferative disease.
AB  - BACKGROUND: Chronic LGL-proliferative disease (LGL-PD) is a clonal expansion of
      cells with large granular lymphocyte (LGL) morphology. In most cases,
      proliferating cells express both suppressor/cytolytic T-cell and natural killer
      (NK) cell surface markers, but other cell phenotypes may be observed. LGL-PD
      lymphocytes have been found to lack or show very low natural killer cell activity
      (NKa). The aim of the present paper is to investigate the underlying mechanisms
      responsible for impaired NKa in a homogeneous group of five selected LGL-PD
      patients with a CD3+, CD8+, CD57+ cell phenotype. RESULTS: In all patients, the
      expanded cell population expressed very low NKa against K562 cell targets, but
      this increased significantly with recombinant human interleukin-2 (rhIL-2) and
      phytohemagglutinin (PHA) activation. Recombinant human alpha-interferon (rhIFN
      alpha) had no significant effect on NKa. Cells displayed normal tumor cell
      binding capacity but failed to release sufficient amounts of functionally active
      natural killer cytotoxic factor(s) (NKCFs) upon interaction with the NK-sensitive
      K562 cells targets. However, they did release soluble cytolytic molecules against
      K562 cells upon activation with PHA. CONCLUSIONS: Our findings provide evidence
      that the defective NKa in LGL-PD patients with the aforementioned phenotype is
      probably due, at least in part, to the inability of expanded lymphocytes to
      release NKCFs upon interaction with NK-sensitive cell targets. Since recognition
      of target cells by patient lymphocytes is not disturbed and the cells are capable
      of producing NKCFs upon activation with PHA, it is probable that the cause of
      this abnormality is located at the level of the activation signal provided by the
      stimulatory target cells. Studies in subcellular level are certainly needed for a
      more precise determination of the underlying defect.

PMID- 8294054
TI  - Serum neopterin levels in haematological malignancies.
AB  - BACKGROUND: Neopterin is an intermediate in the pathway of pteridines released in
      vitro from non proliferating activated cells such as macrophages stimulated with
      interferons. Increased urinary excretion of neopterin has been described in
      conditions of cell-mediated immune activation and in neoplastic diseases,
      including haemopoietic tumours. METHODS: We studied by radioimmunoassay serum
      neopterin levels of 91 patients with haematological malignancies differing in
      diagnosis, stage, treatment, and disease duration. RESULTS: Mean patient
      neopterin (13.5 nmol/L) was increased compared to 69 healthy controls (5.4
      nmol/L, P < 0.001), and individual levels were related to patient survival (P =
      0.006). No relevant differences were found among the various disorders, whilst
      advanced stages and active diseases had higher levels than initial stages and non
      active diseases. Furthermore, off-therapy patients in stable remission did not
      differ from normals. Among subjects on therapy, patients on alpha-interferon had
      a higher percentage of (dose-related) neopterin elevation, in spite of a steady
      disease. CONCLUSIONS: We suggest that serum neopterin dosage has prognostic value
      in staging and follow-up, and may provide a useful tool for monitoring the
      therapy (particularly with biological response modifiers) of haematological
      neoplasias.

PMID- 8294055
TI  - Biological aspects and clinical applications of long-term bone marrow culture: a
      meeting report.

PMID- 8294056
TI  - Selective myeloid aplasia: a long-lasting presentation of an unusual hairy cell
      leukemia variant?
AB  - A rare aleukemic myeloaplastic presentation of hairy cell leukemia (HCL) is
      described. The patient was observed for 11 years and presented a clinical picture
      suggestive of pure white cell aplasia for seven years. Hairy cells (HC) were
      first discovered in the bone marrow, then occasionally in the blood during the
      last four years. A brief course of low-dose alpha interferon promptly induced
      prolonged remission of neutropenia. In our opinion, this case, as few others
      described till now, should be considered a rare HCL variant, an understanding of
      which offers an important clinical opportunity for investigating the myeloid
      inhibitory activity of hairy cells.

PMID- 8294057
TI  - Familial erythrophagocytic lymphohistiocytosis: adverse prognostic significance
      of delayed diagnosis.
AB  - Familial erythrophagocytic lymphohistiocytosis (FEL) is a rare disorder of the
      monocyte-macrophage system, for which an autosomal recessive mode of inheritance
      has been postulated. It is characterized by a dismal prognosis and is peculiar of
      early infancy. Three new cases of infants affected by FEL are reported. All three
      patients were diagnosed about three months after the onset of symptoms, and all
      three died shortly after diagnosis. The need for early diagnosis and prompt,
      intensive cytotoxic chemotherapy is emphasized.

PMID- 8294058
TI  - A hemorrhagic syndrome of the elderly patient caused by anti-factor VIII
      antibodies.
AB  - We report here 2 cases of elderly patients who were admitted to our Department of
      Geriatrics for a hemorrhagic syndrome. The patients were found to be affected by
      a coagulopathy with prolonged activated partial thromboplastin time (aPTT),
      caused by the presence of an acquired inhibitor of Factor VIII. This syndrome,
      due to anti-Factor VIII antibodies, is surely an important clinical entity that
      is not easy to diagnosed, but in concomitance with a hemorrhagic syndrome and
      prolonged aPPT it should always be suspected. In fact, a quick diagnosis is very
      important in order to apply specific treatment as soon as possible.

PMID- 8294059
TI  - Fluconazole prophylaxis and Candida fungemia in neutropenic children with
      malignancies.
AB  - From March, 1990 to February, 1992, we administered fluconazole as antifungal
      prophylaxis at doses of 3-5 mg/kg/day to 40 patients with prolonged and severe
      neutropenia following intensive chemotherapy. Fungemia was observed in 3 out 40
      patients, and all three of them were due to Candida non-albicans strains: two
      Candida parapsilosis and one Candida guilliermondi. In vitro sensitivity tests
      showed that all three isolated strains were susceptible to amphotericin. In one
      case, Candida guilliermondi was tested for sensitivity to fluconazole and found
      to be resistant. We conclude that fluconazole prophylaxis proved effective in
      preventing Candida albicans infections, but it could also contribute to the
      emergence of Candida non-albicans strains. It might be possible that fluconazole
      at higher doses could prevent the selection of less susceptible Candida strains.

PMID- 8294060
TI  - Cryoglobulinemia: a monoclonal gammopathy?

PMID- 8294061
TI  - Measurement of soluble CD4 molecule in chronic lymphoproliferative disorders.

PMID- 8294062
TI  - Hodgkin's disease, splenectomy and secondary leukemia.

PMID- 8294063
TI  - Thrombotic thrombocytopenic purpura: relapse and pregnancy.

PMID- 8294064
TI  - [The scapula flap--overview and personal experiences].
AB  - Since the first report in the literature by Dos Santos in 1980, the scapula flap
      has become one of the most commonly used fascio-cutaneous free flaps. This is due
      to its numerous advantages and its few inconvenients. Because of the constant
      anatomy, the minor donor site defect and its good aesthetic result, the scapula
      flap replaced other more traditional flaps such as the radial forearm or the
      latissimus dorsi flap. Being a flap of the "subscapular artery system", it offers
      the possibility to be harvested "en bloc" with the other flaps of this system for
      complex reconstruction procedures. In our opinion, the scapula flap is the
      treatment of choice to treat cutaneous defects of the lower extremity which could
      not be covered by local flaps. In head-neck reconstruction, the colour and
      texture of the skin offered by this flap is superior to other free flaps. A
      thick, well visible horizontal scar in the donor site is the only real
      inconvenience of the scapula flap. It seems that the parascapula-flap (Nassif et
      al. 1982) which offers the same properties as the scapula flap is on the way to
      replace the scapula flap in the future. After a six-year experience with this
      flap we will present a current concept review and our own experience based on 30
      cases. Moreover, we would like to report on some technical refinements.

PMID- 8294065
TI  - [Relations between donor nerve size and degree of neurotization in the nerve
      transplant--an experimental study].
AB  - The present study was undertaken to investigate whether the number of myelinated
      fibers in a sensory nerve used as an autograft influences the result of nerve
      fiber regeneration in the graft. In 30 rabbits, the left saphenous nerve was used
      as an autograft. It was coapted to the motor branch to the rectus femoris muscle.
      Biopsies from both ends of the graft were taken. Animals were separated into four
      investigation groups, which were reexamined 3, 6, 9 and 12 months after the
      grafting procedure. Biopsies for histological and morphometric examination were
      again taken from the proximal and the distal part of the grafts. Thus, the number
      of myelinated nerve fibers in the different specimens could be obtained by
      computer-assisted image analysis. At the proximal end of the original saphenous
      nerve, the number of fibers varied between 1032 and 3100 (mean 2145).
      Corresponding data obtained from the distal end ranged from 1044 to 3084
      myelinated nerve fibers (mean 1724). Fiber numbers in the proximal and distal
      parts of the grafts before and after regeneration were correlated to each other.
      In the whole population of specimens (correlation coefficient +/-0) as well as in
      the experimental subgroups, the quantitative success of neurotization in the
      grafts did not depend to a high degree upon the fiber numbers in the original
      saphenous nerve. The correlation coefficient for the proximal part of the graft
      exceeded 0.5 to only three and twelve months after grafting, but did not reach a
      level of statistical significance. In the distal part of the graft, the
      coefficient for a linear correlation was always less than 0.45.

PMID- 8294066
TI  - [Can muscle transposition of an antagonist modify regeneration of the peroneal
      nerve?].
AB  - The prognosis after injury and microsurgical repair of the peroneal nerve is
      poor. However, clinical experience seems to indicate better results if nerve
      repair or neurolysis is combined with transposition of the tibialis posterior
      muscle. This hypothesis was tested in 20 rabbits by severing the peroneal nerve
      of one lower extremity. Nerve repair with muscle transposition was performed in
      ten rabbits and nerve repair without muscle transposition in the remaining ten
      animals. Six to twelve months later, histological and histochemical studies of
      nerve and muscle tissue were performed. No significant differences between the
      two groups could be determined.

PMID- 8294067
TI  - [Clinical and neurologic results after surgical management of the cubital tunnel
      syndrome].
AB  - Fourty-two patients suffering from cubital tunnel syndrome were reexamined after
      anterior subcutaneous transposition of the ulnar nerve. In 25 patients,
      electrophysiological results could be compared pre- and postoperatively. Only few
      patients recovered completely, however, electrophysiological results showed an
      improvement in most of the patients. Sensory velocity proved to be more sensitive
      than motor velocity. We advice patients for early operation to avoid aggravation
      of symptoms, even if remission will be incomplete.

PMID- 8294068
TI  - [Tension relief in nerve sutures].
AB  - In short defects up to 25 mm following injuries of peripheral nerves, a method of
      suturing is outlined using two PDS-ribbons which are sutured to the epineurium,
      reducing tension at the site of coaptation. The ribbons are 20 mm long and 1 mm
      wide. They distribute and reduce the tension at the suture site and permit early
      mobilisation. They induce a restricted scar on the epineurium, maintaining
      tension relief. Of 105 nerves sutured with this method results have been obtained
      in 53 cases with an average follow-up time of at least 12 months. The overall
      results: Median nerve (N = 28) S3-4 64.5%, M3-5 82%. Ulnar nerve (N = 25) S3-4
      77%, M3-5 84.5%. Clean cuts had the best results, secondary sutures (with an
      average interval of 30 days) were somewhat better than primary sutures.

PMID- 8294069
TI  - [Functional treatment of basal joint fractures of three-joint fingers].
AB  - Phalangeal fractures have up to now always been treated using a conservative
      static form of splint. Open reduction and stabilisation is preferred in the case
      of injuries with severe displacement, shortening, open fractures and joint
      involvement. In this study, we have shown the results of 86 proximal phalangeal
      fractures that were treated with "dynamic splinting". In the "intrinsic plus"
      position a dorsopalmar plaster splint is affixed in combination with a Bedford
      double finger stall, splinting the injured finger securely to its neighbour.
      Clinical and X-ray results were evaluated. Oblique, rotational and transverse
      fractures can be reduced and treated showing good results with dynamic splinting.
      Bending fractures cannot always be treated with this method. Especially basal
      fractures with dorsal comminution can be problematic. Comminuted fractures can
      only be treated with dynamic splinting if they have been primarily adequately
      reduced. Intraarticular condylar fractures have to be treated surgically. Our
      results have also shown that the fingers still are freely mobile even when the
      bone has not healed in an anatomical position.

PMID- 8294070
TI  - [Opposition-plasty after brachial plexus lesions by osteosynthesis].
AB  - Secondary reconstruction of lost muscle function in brachial plexus injuries is
      performed by dynamic muscle and tendon transposition, by free microvascular
      muscle transplantation and by static surgical procedures. In cases of weak
      function of the finger flexors, static opponensplasty is required. In these cases
      our procedure is the internal fixation of the base of the metacarpal I to the
      base of the metacarpal II without stabilisation of cancellous bone. From 1987 to
      1992 we operated 15 patients by this procedure. Results are showing sufficient
      stabilisation and good function.

PMID- 8294071
TI  - [A reduction hook for the Bennett dislocation fracture].

PMID- 8294072
TI  - [Federal public health service--quo vadis?].

PMID- 8294073
TI  - [The AIDS-blood scandal: Seehover plays with hidden cards. Is a public health
      administrator permitted to purposely incite hysteria?].

PMID- 8294074
TI  - [Comparison of conventional versus 24-hour blood pressure measurement. How often
      do variations in diagnostic/therapeutic evaluation occur?].
AB  - QUESTION: The question as to whether and to what extent 24-hour blood pressure
      measurement (Holter monitoring) is capable of improving the diagnosis and
      treatment of arterial hypertension was investigated. METHODS: For this purpose,
      50 patients with the diagnosis--based on random blood pressure measurement--of,
      or receiving treatment for, hypertension were referred to our hospital by general
      practitioners. In 26 patients, the diagnosis hypertension, and in 24 patients the
      "well-controlled hypertension" were checked with the aid of 24-hour ambulatory
      monitoring. RESULTS: Of the patients referred with the diagnosis hypertension,
      27% were shown by 24-hour blood pressure measurement not to be suffering from
      hypertension. The treatment of the 24 patients considered to be "well-controlled
      hypertensives" was validated by 24-hour blood pressure measurement in only 13
      cases.

PMID- 8294075
TI  - [Influenza vaccination--yes or no?].

PMID- 8294076
TI  - [Influenza: incidence and costs of inpatient treatment].
AB  - In Austria, in 1990, a total of 3,808 patients with influenza were hospitalized
      for treatment (49.34/100,000). The age-specific incidence rates show three peaks:
      < 5 years (132.05/100,000), adolescents (15 to 19-year-olds, 111.5/100,000), old
      age groups (85-year-olds, 102.7/100,000). Complications occurred in 1,479 (38.8%)
      patients, including 846 cases (57.2%) with "other complications" of the
      respiratory tract, 365 cases (24.7%) of pneumonia, and 268 cases (18.1%) with
      manifestations affecting other organs. The 3.808 patients spent a total of 34,684
      days in hospital. The overall costs of hospital treatment were some 104 million
      Austrian schillings (approx. 15 million German marks)--per patient on average
      26,700 schillings (approx. 3,840 marks); per pneumonia patient 61,200 schillings
      (approx. 8,743 marks).

PMID- 8294077
TI  - [Viral infections--clinical pictures and laboratory diagnosis. Part 2: Coxsackie
      B virus, echovirus, enteroviruses, EBV, FSME virus and yellow fever virus].

PMID- 8294078
TI  - [Ceftriaxone in malignant occlusive jaundice. Studies of serum and bile
      concentration in disordered bile excretion].
AB  - METHODS: In 12 patients with inoperable malignant obstructive jaundice,
      percutaneous transhepatic biliary drainage was performed to decompensate the bile
      ducts. For a period of 7 days, the patients received a single daily i.v. dose of
      1 g CFTX, and the serum and bile concentrations were measured at defined
      intervals. RESULTS: The dose sufficed to kill about 85% of the expected
      organisms. Although an accumulation of the substance as documented under
      conditions of normal bile flow was not demonstrable under cholestatic conditions,
      effective levels were nevertheless found in the bile and showed a tendency to
      increase with increasing bile flow.

PMID- 8294079
TI  - The NMDA receptor complex.
AB  - The synaptic responses elicited by glutamate and aspartate in the CNS are
      mediated by distinct groups of receptors which include the ionotropic NMDA
      receptor. The NMDA receptor is activated by high-strength synaptic input and
      produces relatively sustained depolarization which can lead to repetitive burst
      firing. These characteristics allow it to be involved in the maintainance of
      rhythmic neuronal activity and in the modulation of synaptic efficacy and
      plasticity. Overstimulation of the NMDA receptor appears to play a pivotal role
      in the physiopathology of ischemic brain injury. The NMDA receptor contains an
      integral cationic channel which is highly permeable to Ca2+ as well as to Na+ and
      K+. This receptor has several domains in addition to the NMDA recognition site:
      i) a divalent cation binding site within the channel pore, at which Mg2+ ions
      bind, ii) a binding site recognized by dissociative anesthetics and MK-801 within
      the channel; and iii) modulatory sites sensitive to glycine, Zn2+ and polyamines.
      The NMDA receptor is strictly controlled by Mg2+ ions in a voltage-dependent
      manner. Moreover, it is modulated by protons, by changes in the redox state and
      by endogenous physiological substances, eg NO and arachidonic acid. Selective
      antagonists now exist for the NMDA recognition site and glycine and polyamine
      modulatory sites. Molecular cloning of the NMDA receptor has identified a subunit
      termed NMDA-R1 and four additional subunits (NMDA-R2A through NMDA-R2D).
      Functionally distinct NMDA receptor subtypes are formed by heteromeric assembly
      of NMDA-R1 with NMDA-R2 subunits. NMDA receptor subunits contain consensus
      phosphorylation sites for protein kinases at the cytoplasmic domain. The high
      Ca2+ permeability and sensitivity to channel block by Mg2+ are imparted by
      asparagine residues in a putative channel-forming segment of the protein
      transmembrane 2. The knowledge of the molecular structure of the NMDA receptor
      will help to understand the molecular mechanisms responsible for its regulatory
      features and the molecular bases of neurotoxicity.

PMID- 8294080
TI  - Nitric oxide: an ubiquitous messenger.
AB  - During the last decade, a multitude of experimental arguments have led to the
      concept that EDRF is nitric oxide (NO), a messenger not only involved in the
      control of vasomotor tone but also in vascular homeostasis, neuronal and
      immunological functions. Regardless of its origin, endogenous NO is produced
      through the conversion of L-arginine to L-citrulline by NO-synthase (NOS) from
      which several isoforms have recently been isolated, purified and cloned. NOS-type
      I (isolated from brain) and type III (isolated from endothelial cells) are termed
      "constitutive-NOS" and produce picomolar levels of NO from which only a small
      fraction elicits physiological responses. These isoforms are regulated by Ca(2+)
      calmodulin with NADPH, FAD/FMN and tetrahydrobiopterin as co-factors and reveal a
      high degree of homology with the amino-acid sequence of cytochrome P450 reductase
      within the C-terminal domain. Functionally, neuronal-NOS type I is important in
      neurotransmission (modulation of NMDA receptor), the central control of vascular
      homeostasis and possibly learning and memory. In the peripheral nervous system,
      NOS appears to be linked to nonadrenergic noncholinergic (NANC) neuronal
      pathways. Endothelial-NOS type III is essential for the control of vascular tone
      in response to the release of endogenous mediators, although shear stress is the
      major trigger of endothelial-NOS activity under physiological conditions. NOS
      type III also contributes to the prevention of abnormal platelet aggregation. NOS
      types II and IV (isolated from macrophages) are Ca(2+)-calmodulin independent and
      are termed "inducible-NOS" since their activation is only promoted under
      pathophysiological situations where macrophages exert cytotoxic effects in
      response to cytokines. In contrast with NOS-types I and III, activation of NOS
      type II in these cells induces the formation of nanomolar levels of NO which act
      as a defense mechanism of the immune system. Dysfunctions of the L-arginine-NO
      pathway have been characterized in multiple diseases (atherosclerosis,
      hypertension, diabetes, sepsis, cerebral ischemia, etc) and the design of more
      selective activators/inhibitors of NOS isoforms is a new challenge for the
      understanding of their pathophysiology and treatment.

PMID- 8294081
TI  - Influence of renal function on the pharmacokinetics of diacerein after a single
      oral dose.
AB  - The pharmacokinetics of diacerein (a new anti-inflammatory analgesic antipyretic
      drug) following a single oral dose of 50 mg was studied in 12 healthy volunteers
      and two groups of eight patients with mild or severe renal insufficiency.
      Statistical analysis using a Kruskal-Wallis rank sum test showed a significant
      difference between the three groups for the following parameters. In severely
      uraemic patients, median AUC0-infinity was multiplied by a factor of ca 2: 40.5
      mg h/l versus 21.3 in healthy subjects, P = 0.04; and t1/2 was prolonged by the
      same factor: 9.6 h versus 4.3 in the control group, P = 0.003. Apparent drug
      availability and renal clearance assessed through urinary data decreased with
      renal failure, respectively: 14.5% and 0.045 l/h versus 35.4% (P = 0.01) and 0.13
      l/h (P = 0.008) in healthy subjects. Amounts of glucuro and sulfo conjugates in
      urine were lower in severely uraemic patients. Intermediate values were observed
      for mildly uraemic patients. Other parameters: lag-time, Cmax, tmax, Vss/F,
      urinary glucuro- to sulphoconjugate ratios did not change significantly. Apparent
      total clearance of rhein was poorly correlated with creatinine clearance and this
      was related to a decrease of non-renal clearance of rhein in renal insufficiency.
      It was concluded that, from a pharmacokinetic point of view, a reduction (50%) in
      the maintenance dosage of diacerein should be considered in severe renal failure.

PMID- 8294082
TI  - Indapamide inhibits endothelium-dependent contractions in the aorta of the
      spontaneously hypertensive rat.
AB  - Experiments were designed to determine whether or not indapamide, an
      antihypertensive agent with vasodilator properties, inhibits endothelium
      dependent contractions. Rings of aortae with and without endothelium from
      spontaneously hypertensive rats (SHR) were suspended in conventional organ
      chambers for the measurement of isometric force. Acetylcholine and adenosine
      diphosphate-beta-S in the presence of a nitric oxide synthase inhibitor, caused
      endothelium-dependent contractions, which were inhibited by indapamide. The
      compound (10(-4) M) also slightly reduced the contractions of rings without
      endothelium evoked by U-46,619, which activates thromboxane-endoperoxide
      receptors. These results demonstrate that indapamide inhibits endothelium
      dependent contractions in the SHR aorta, and suggest that the inhibition is due,
      at least in part, to the action of the drug on the hypertensive vascular smooth
      muscle.

PMID- 8294083
TI  - Dopaminergic modulation of visual sensitivity in man.
AB  - A large body of experimental evidence supports the hypothesis that dopamine is a
      functional neuromodulator at many levels of the visual system. Intrinsic
      dopaminergic neurons were characterized in most mammalian retina, including man.
      These neurons give rise to a dendritic plexus covering the retina. Thus, dopamine
      seems to be involved in the organization of the ganglion cell and the bipolar
      cell receptive fields and modulates physiological activity of photoreceptors,
      both processes which underlie sensitivity and spatial selectivity of visual
      processing in the early stage of the visual system. Moreover, few data are now
      available concerning the functional significance of dopaminergic modulation of
      visual sensitivity in man. Parkinson's disease is a specific disorder of central
      dopaminergic systems. Abnormalities in the pattern-evoked potentials and
      electroretinogram have been found in parkinsonian patients. Contrast sensitivity,
      a useful tool for measuring visual spatio-temporal sensitivity in man, has also
      been shown to be modified due to this affection. Dynamic contrast sensitivity is
      primarily decreased in these patients, distinguishing them from the normal aging
      process. Because these modifications in shape of the contrast sensitivity
      function are reversed by L-Dopa, and that neuroleptic administration could
      reproduce them in schizophrenia patients, it was suggested that dopamine might
      tune the contrast sensitivity function in man. We have recently shown that
      subcutaneous apomorphine induces changes in contrast sensitivity in healthy
      volunteers, which preferentially affect motion sensitivity. These dopaminergic
      sensitive modifications in the shape of the contrast sensitivity function might
      reflect a change in the range of sensitivity of the visual system, both in
      dynamic and spatial properties. This could be explained by a modification in the
      spatial and dynamic properties of the ganglion cell responses in the retina.
      Moreover, we suggest both from our results and from the review of the literature
      that human psychophysical data confirm the hypothesis that dopamine may be
      involved in light retinal adaptation, as light-induced and dopamine-induced
      modifications in the shape in the contrast sensitivity function are quite
      similar.

PMID- 8294084
TI  - Lack of yohimbine effect on ambulatory blood pressure recording: a double-blind
      cross-over trial in parkinsonians with orthostatic hypotension.
AB  - Yohimbine is an alpha 2-adrenergic antagonist which has been proposed for the
      treatment of orthostatic hypotension (OH). We investigated in a double-blind
      placebo-controlled crossover trial the effects of yohimbine (2 mg tid) on blood
      pressure (BP) and heart rate (HR) using ambulatory monitoring of blood pressure
      (AMBP) in 17 patients (69 +/- 5 years) with Parkinson's disease (PD) suffering
      from non drug-induced OH. At the end of each sequence of 4 weeks, mean systolic
      (SBP) and diastolic (DBP) BP and HR (+/- SD), BP variability (coefficient of
      variation of the mean) and nychtemeral rhythm were calculated for day-time (09:00
      19:00 h) and night-time (23:00-06:00 h). OH related to PD was characterized by:
      i) loss of the nychtemeral rhythm of BP (night/day ratio: 1.18 +/- 0.14) but not
      of HR (night/day ratio: 0.87 +/- 0.04), ii) high variability of BP during day
      time and iii) post-prandial hypotension (12 out of 17 patients). There was no
      significant difference in AMBP parameters between baseline, yohimbine and placebo
      periods. This study shows that AMBP is a simple and reproducible method to assess
      the effects of drugs used in the management of OH on BP parameters (mean values
      and variability) and that yohimbine is not effective to correct OH of PD. Future
      studies must investigate other more selective alpha 2-adrenergic antagonists.

PMID- 8294085
TI  - Hepatitis C viremia in chronic liver disease: relationship to interferon-alpha or
      corticosteroid treatment.
AB  - We assessed the pattern of hepatitis C viremia in chronic liver disease by
      studying 100 hepatitis C virus antibody-positive patients: 48 with chronic
      hepatitis, 21 with cirrhosis and 31 with hepatocellular carcinoma and cirrhosis.
      Serum hepatitis C virus RNA was detected by means of both the conventional nested
      polymerase chain reaction and a newly developed assay based on branched DNA that
      can also quantify viremia. Hepatitis C virus RNA was found in 94 of 100 patients
      with polymerase chain reaction and in 71 of 100 patients with branched-DNA (p <
      0.001). Mean viremia level (x 10(3) genome equivalents/ml +/- S.D.), as assessed
      with the branched-DNA test, was 5,700 +/- 7,618 in the 48 patients with chronic
      hepatitis, 3,340 +/- 3,633 in the 21 patients with cirrhosis and 1,768 +/- 2,770
      in the 31 patients with hepatocellular carcinoma (p < 0.02). We also analyzed
      retrospectively the relationship between viremia and treatment. Fifty-five
      patients (41 chronic hepatitis, 14 cirrhosis) underwent interferon-alpha
      treatment. Mean viremia level was comparable among the 30 responders (5,644 +/-
      8,207) and the 25 nonresponders (5,519 +/- 6,208) to interferon, but it was
      significantly lower (1,841 +/- 1,864) in the 12 of 30 responders (11 chronic
      hepatitis, 1 cirrhosis) who maintained remission up to 1 yr after cessation of
      interferon treatment. Fourteen patients (7 chronic hepatitis, 7 cirrhosis) with
      autoantibodies (12 antinuclear, 2 anti-liver-kidney microsomal) were treated with
      prednisone. The mean viremia level significantly increased after 3 mo of
      treatment, even in face of ALT decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294086
TI  - T-cell response to structural and nonstructural hepatitis C virus antigens in
      persistent and self-limited hepatitis C virus infections.
AB  - Twenty-nine patients with chronic hepatitis C and 15 asymptomatic hepatitis C
      virus antibody-positive subjects who clinically recovered from hepatitis C virus
      infection were studied for their peripheral blood lymphomononuclear cell
      proliferative response to hepatitis C virus structural and nonstructural antigens
      (core, envelope, nonstructural 4 and nonstructural 5) expressed in yeast as
      superoxide dismutase fusion proteins, in an initial attempt to define some of the
      features of the virus-specific immune response. Hepatitis C virus core was the
      most immunogenic antigen for human leukocyte antigen class II-restricted T cells
      in both groups of patients studied, and the proliferative response to it was the
      most vigorous and the most frequently expressed in comparison with the other
      antigens tested. The specificity of the results was supported by the lack of
      response to hepatitis C virus antigens by healthy uninfected controls and
      confirmed by recognition of recombinant core proteins of different origin (yeast
      and baculovirus) by polyclonal T-cell lines produced by T-cell stimulation with
      yeast-derived core. Each of the antigens tested was able to induce significant
      although variable levels of proliferative response, indicating that all can be
      immunogenic at the T-cell level. Significant proliferative responses to core,
      nonstructural 4 and nonstructural 5 antigens were more frequently detected in
      subjects who were able to eradicate infection than in patients with chronic
      hepatitis C, although the difference was statistically not significant. No
      difference was observed between the two groups of patients with respect to the
      response to the putative envelope antigens.

PMID- 8294087
TI  - Buoyant density of hepatitis C virus recovered from infected hosts: two different
      features in sucrose equilibrium density-gradient centrifugation related to degree
      of liver inflammation.
AB  - Hepatitis C virus is reported to have a low buoyant density in sucrose. To
      determine the density of hepatitis C virus in the circulation of infected hosts
      and its association with the degree of liver inflammation, we examined serum
      samples from 10 patients who were positive for both hepatitis C virus antibody
      (C100 antigen) antibody and serum hepatitis C virus RNA. After the serum was
      ultracentrifuged in sucrose density gradient (10% to 60%), the hepatitis C virus
      RNA titer in each collected fraction was quantified by means of competitive
      reverse transcription-polymerase chain reaction. In samples from five blood
      donors, the hepatitis C virus RNA titer had a single peak at fractions with
      densities of 1.08 to 1.11 gm/ml. In samples from five patients with ALT
      abnormalities, the titer had two peaks at fractions with 1.09 to 1.10 gm/ml and
      1.22 to 1.25 gm/ml. After the selected samples were treated with detergents and
      ultracentrifuged, the titer in the 1.08 to 1.11 gm/ml fractions decreased and
      that in the 1.22 to 1.25 gm fractions increased. This result implied that the
      hepatitis C virus density changed with removal of the viral envelope by lipid
      solvents. Thus the buoyant density of hepatitis C virus in sucrose was 1.08 to
      1.11 gm/ml for an intact virion and 1.22 to 1.25 gm/ml for what was presumed to
      be a nucleocapsid. These results demonstrated that HCV virion is a dominant form
      in the circulation of blood donors without ALT abnormalities. In patients with
      liver inflammation HCV particles with higher densities of 1.22 to 1.25 gm/ml
      coexist with virion in the circulation, which might be presumed nucleocapsids.

PMID- 8294088
TI  - Quantitative assessment of serum IgM anti-HBc in the natural course and during
      interferon treatment of chronic hepatitis B virus infection.
AB  - Serum IgM anti-HBc was determined in 135 chronic HBsAg carriers with various
      categories of histological activity on liver biopsy and hepatitis B serological
      profile. Thirty-three patients were treated with interferon-alpha to investigate
      the correlation between serum IgM anti-HBc with histological activity and viral
      replication, to evaluate the usefulness of pretreatment IgM anti-HBc as a
      predictor of a successful response to interferon-alpha and to examine the IgM
      anti-HBc response during this treatment. All 53 patients with chronic active
      hepatitis with either wild-type (n = 42) or precore mutant variant HBV infection
      (n = 11) had an IgM anti-HBc index greater than 0.300 compared with 7.4% (2 of
      27) of the chronic HBsAg/HBeAg-positive carriers with chronic persistent
      hepatitis, 10% (3 of 30) of the anti-HBe-positive asymptomatic carriers and none
      of the 25 patients with hepatitis D virus-positive chronic active hepatitis (p <
      0.0001). Pretreatment IgM anti-HBc index was greater than 0.300 in 82.4% (14 of
      17) of HBeAg/HBV DNA-positive patients who seroconverted after interferon-alpha
      treatment compared with 25% (4 of 16) of the patients who did not seroconvert (p
      = 0.0013), whereas an elevated pretreatment AST was present in only 52.9% (9 of
      17) of responders and in 37.5% (6 of 16) of nonresponders (p = 0.42). Serial
      testing of IgM anti-HBc in these 33 patients during interferon-alpha treatment
      showed a significant rise in IgM anti-HBc in all responders, which followed the
      AST flare-up but preceded the time of the HBeAg to anti-HBe
      seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294089
TI  - Central blood volume in cirrhosis: measurement with radionuclide angiography.
AB  - In patients with cirrhosis a diminished effective central arterial blood volume
      associated with systemic arterial vasodilation has been proposed as the mechanism
      that initiates renal sodium retention. Furthermore, total central blood volume
      has recently been reported as reduced in cirrhosis, and the controversy over the
      stimulus for sodium retention in cirrhosis remains. The aim of this study was to
      assess the central blood volume with radionuclide angiography to determine
      whether there is effective arterial underfilling in cirrhosis. Twenty-nine
      patients (13 with and 16 without ascites) and 10 age- and sex-matched control
      subjects were studied under metabolic conditions. Radionuclide ventricular volume
      and total central blood volume were determined from gated images, taking into
      account the 99Tc count activity per milliliter of blood volume and attenuation.
      The pulmonary volumes were similarly derived.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294090
TI  - Early and late changes in fasting and absorptive plasma amino acids and ammonia
      after distal splenorenal shunt in cirrhosis.
AB  - Levels of plasma amino acids, ammonia, glucagon and insulin and their 5-hr
      responses to a protein feeding were evaluated before and sequentially (3 mo and 1
      yr) after distal splenorenal shunt in 10 patients with cirrhosis belonging to
      Child-Pugh's class A or B. An index of glucagon effectiveness (plasma
      glucose/glucagon) was also calculated. These parameters were related to liver
      test results, portal vein diameter and mental state, and they were compared with
      those found in seven patients undergoing sclerotherapy of esophageal varices with
      comparable liver function (control group). Liver test results and levels of
      plasma insulin did not change in either group. Shunt significantly increased
      levels of fasting tyrosine, methionine, ornithine, arginine, histidine, ammonia
      and glucagon with respect to the control group; it also significantly decreased
      levels of leucine, valine, glucagon effectiveness and portal vein diameter. The
      elevation of levels of tyrosine, ammonia and the sum of arginine and ornithine
      was correlated directly with the increase in glucagon and inversely with the
      decline in glucagon effectiveness. Tyrosine increase was also correlated with the
      reduction of portal vein diameter. One shunted patient showed mild hepatic
      encephalopathy. Protein feeding did not worsen the mental state of patients
      before and after the operation. Surgery significantly increased the 5-hr response
      to the meal of gluconeogenic amino acids; its rise was again correlated with the
      changes in glucagon plasma levels and effectiveness. Although the absorptive
      levels of plasma ammonia were significantly higher 1 yr after surgery, its 5-hr
      response barely rose. In cirrhotic patients with a relatively preserved liver
      function, distal splenorenal shunt progressively worsened the fasting plasma
      profile of nitrogen compounds and the response to protein ingestion of
      gluconeogenic amino acids. The decline of portal blood flow and glucagon
      effectiveness may be causal factors. Despite this, the "cerebral" tolerance to a
      moderate oral load of protein was not reduced by surgery.

PMID- 8294091
TI  - Acute fatty liver of pregnancy and long-chain 3-hydroxyacyl-coenzyme A
      dehydrogenase deficiency.
AB  - The pathogenesis of acute fatty liver of pregnancy is unknown, but similarities
      in the clinical presentation and the histological appearance of the liver with
      those found in children with metabolic defects in the intramitochondrial beta
      oxidation pathway of the liver suggest that a disturbance in hepatic fatty acid
      oxidation may play a role. We report a woman with acute fatty liver of pregnancy
      who gave birth to a seemingly normal full-term infant who was seen at 4 mo of age
      with hypoglycemia, coma and profound hepatic steatosis. The infant had a defect
      in fatty acid oxidation, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase
      deficiency, and the mother proved to be heterozygous for this metabolic
      condition. We hypothesize that the interaction of an affected fetus with a female
      heterozygous for this defect in fatty acid oxidation in the late third trimester
      accounts for some cases of acute fatty liver of pregnancy.

PMID- 8294092
TI  - Diuretics vs. paracentesis followed by diuretics in cirrhosis: effect on ascites
      opsonic activity and immunoglobulin and complement concentrations.
AB  - Ascitic fluid opsonic activity and ascitic fluid C3 concentrations are important
      protective factors against spontaneous bacterial peritonitis. This randomized
      controlled study was performed to compare the effect of diuretic administration
      alone vs. single large-volume therapeutic paracentesis followed by administration
      of diuretics on ascitic fluid opsonic activity and on ascites and serum
      immunoglobulin and complement concentrations in patients with alcoholic cirrhosis
      and tense ascites. Twenty-one patients were randomly allocated to two groups:
      group 1 included 11 patients who were treated with diuretics alone, and group 2
      included 10 patients who were treated with single large-volume therapeutic
      paracentesis (5 to 6 L of ascites removed) followed by diuretics. Ascitic fluid
      opsonic activity and serum and ascites immunoglobulin and complement
      concentrations were measured at the beginning and at the end of treatment. The
      ascitic fluid opsonic activity increased significantly in patients treated with
      diuretics alone (p < 0.05), whereas in the group of patients treated with
      therapeutic paracentesis followed by diuretics, the ascites opsonic activity
      remained stable. Although ascitic fluid IgG, IgA and C3 concentrations increased
      significantly in patients treated with diuretics alone (p < 0.05), ascitic fluid
      C3 concentration significantly decreased in patients from group 2 (p < 0.05),
      whereas IgG and IgA concentrations remained unchanged. However, in both groups of
      patients serum immunoglobulin and complement concentrations remained unchanged.
      This study suggests that in cirrhotic patients with tense ascites, treatment with
      diuretics alone may have the potential advantage over single large-volume
      therapeutic paracentesis followed by the administration of diuretics of providing
      better protection from spontaneous bacterial peritonitis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8294093
TI  - Reperfusion injury, antioxidants and hemodynamics during orthotopic liver
      transplantation.
AB  - Endothelial injury occurs as a result of oxygen free radical production after
      ischemia and reperfusion of transplanted livers, causing hemodynamic disturbance.
      Patients with chronic liver disease generally have low levels of fat-soluble
      vitamins, which have important antioxidant roles. We therefore assessed
      circulating levels of the antioxidants vitamin A, vitamin E, beta-carotene and
      lycopene, indices of lipid peroxidation and hemodynamic changes during elective
      orthotopic liver transplantation in 12 patients. We found that initial
      antioxidant levels were severely depleted compared with healthy subjects, and in
      some patients carotene and lycopene levels were undetectable. Increased lipid
      peroxidation was also evident, as shown by thiobarbituric acid-reactive
      substances. On reperfusion of the liver graft, vitamin A and E levels fell (p <
      0.01) and were associated with decreases in systemic vascular resistance (p <
      0.02). These data show that patients undergoing liver transplant have lowered
      antioxidant defenses and evidence of free radical damage, which compound the
      additional insult of reperfusion injury. Antioxidant therapy in these patients
      before transplantation may ameliorate the effects of reperfusion.

PMID- 8294094
TI  - Augmentation of portal blood flow improves function of human cirrhotic liver.
AB  - In cirrhotic livers, the intrahepatic resistance is increased and drug
      elimination and portal transhepatic flow are decreased. The aim of our work was
      to study the effect of a twofold increase in portal blood flow during 2 hr on the
      hemodynamic parameters, drug elimination and hepatic viability in eight isolated
      perfused human cirrhotic livers. Using an oxygenated recirculating system with
      independent arterial and portal flows, we perfused livers with Kreb's buffer
      bicarbonate solution, bovine serum albumin (20 gm.L-1) and human red blood cells
      (hematocrit 20%). The flow was maintained at a basal level of 0.713 +/- 0.19
      L/min for 1 hr and then increased and maintained for 2 hr at twice the basal
      flow. Portal pressure-portal flow curve slopes were linear (27.04 +/- 21.06 mm
      Hg.L-1 x min; range = 6.43 to 60.8) and correlated with intrahepatic resistance
      during the basal-flow period (r = 0.87, p < 0.01). Parameters registered during
      the basal- and high-flow periods were compared by use of Student's t test: portal
      pressure increased from 23.5 +/- 7 to 37.3 +/- 16.7 mm Hg (p < 0.05); arterial
      pressure increased from 80.3 +/- 19 to 103.5 +/- 26 mm Hg (p < 0.005); hepatic
      artery flow resistance increased 31.9% (from 690.1 +/- 218 to 899.4 +/- 269 mm
      Hg.L-1 x min; p < 0.005); indocyanine green clearance increased by 28.2% (from
      86.0 +/- 58.3 to 109.2 +/- 74.8 ml.min-1 x kg liver-1; p < 0.04). No significant
      differences were observed in enzyme release, biliary flow (n = 5) and oxygen
      consumption. Histological examinations demonstrated sinusoidal dilatations in six
      of eight cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294095
TI  - Gender-dependent reduction of spontaneous motor activity and growth in rats
      subjected to portacaval shunt.
AB  - Alterations in behavior are frequently described in rats subjected to portacaval
      shunt. Previous work has reported reduced spontaneous motor activity in various
      settings (nighttime, red light, decreased illumination) in this animal model. We
      investigated this phenomenon in rats of both genders subjected to portacaval
      shunt to determine whether our previously observed divergent growth patterns
      (males reduced, females unchanged) had any impact on the alterations in
      spontaneous motor activity in this model. Dietary intake, growth, motor activity
      and serum ammonia and amino acid concentrations were measured, in addition to
      final liver and spleen weights, in each animal after 3 to 4 wk of observation.
      Our results reconfirm the differential impact of portacaval shunt on growth in
      male (35% reduction p < 0.01) but not female rats (5% reduction, NS) compared
      with their respective-gender sham-operated controls. In addition, spontaneous
      motor activity was significantly reduced in male (congruent to 50%, p = 0.01) but
      not female rats subjected to portacaval shunt. The reduction of activity in male
      rats subjected to portacaval shunt did not correlate with any of the measured
      biochemical data or calculated nutritional/growth parameters. Thus we observed
      gender-dependent reduction in spontaneous motor activity after portacaval shunt
      in the rat. The mechanism for this phenomenon is unknown, but it is easily
      investigated with this reproducible model.

PMID- 8294096
TI  - Hepatocarcinogenesis is the sequel to hepatitis in Z#2 alpha 1-antitrypsin
      transgenic mice: histopathological and DNA ploidy studies.
AB  - Z mutant-associated alpha 1-antitrypsin deficiency in human beings leads to
      hepatitis and, in some cases, hepatocellular carcinoma. To begin to delineate the
      molecular basis for the development of hepatocellular carcinoma in alpha 1
      antitrypsin deficiency, we previously developed transgenic mice using human alpha
      1-antitrypsin M and Z genomic clones. High-copy Z lineage mice (12 gene
      copies/haploid mouse genome; "Z#2") had hepatocytes distended with human alpha 1
      antitrypsin deficiency globules. Hepatitis was present, and the morphological
      changes mimicked those observed in human alpha 1-antitrypsin deficiency-related
      liver disease. The numbers of hepatocytes containing alpha 1-antitrypsin globules
      decreased with age, and alpha 1-antitrypsin-negative nodular aggregates of
      hepatocytes increased in number and size. Hepatocytic dysplasia occurred as early
      as 6 wk and was almost universally present at 1 yr. Nodules of dysplastic cells
      demonstrating aneuploidy were seen as early as 10 wks. These became persistent,
      proliferative lesions. Dysplasia and aneuploidy distinctly increased with time
      and advancing microscopic stage as lesions progressed to malignancy. Tumors were
      seen after 1 yr as adenomas, which are aneuploid and most likely well
      differentiated hepatocellular carcinoma, and borderline malignant lesions; and,
      in 82% of Z#2 mice 16 to 20 mo old, as invasive hepatocellular carcinoma. These
      observations suggest but do not conclusively prove that hepatocellular carcinoma
      in alpha 1-antitrypsin deficiency and other hepatic disorders arises as a result
      of a common, endogenously stimulated pathway for hepatocellular carcinogenesis.

PMID- 8294097
TI  - Characterization of the antiviral effects of 2' carbodeoxyguanosine in ducks
      chronically infected with duck hepatitis B virus.
AB  - This study was carried out to evaluate benefits and limitations of long-term
      therapy of hepatitis B virus infections with a nucleoside analog inhibitor of
      virus replication. The model we used was the domestic duck chronically infected
      with duck hepatitis B virus by in ovo infection. 2' Carbodeoxyguanosine was used
      as an inhibitor of viral DNA synthesis. In all animals examined there was a
      reduction in virus production during therapy. A dose of 2' carbodeoxyguanosine of
      10 micrograms/kg every other day reduced the number of infected hepatocytes from
      greater than 95% to 25% to 50% in less than 3 mo, whereas a 10-fold higher dose
      produced a decline to less than 10%. Histological evaluation revealed mild to
      moderate liver injury in ducks receiving the higher dose of 2'
      carbodeoxyguanosine, suggesting that disappearance of infected hepatocytes may
      have been accelerated by a toxic effect of the drug. Drug treatment did not
      completely eliminate duck hepatitis B virus from any duck, and replication was
      restored in all hepatocytes within a few weeks to several months after antiviral
      therapy was terminated. Our results suggest that elimination of a chronic
      infection with a single inhibitor of replication may be difficult in a host that
      lacks an antiviral immune response capable of eliminating at least a portion of
      the infected hepatocytes and of ultimately producing antibodies capable of
      neutralizing residual virus.

PMID- 8294098
TI  - Transforming growth factor-beta 1 and mannose 6-phosphate/insulin-like growth
      factor-II receptor expression during intrahepatic bile duct hyperplasia and
      biliary fibrosis in the rat.
AB  - These studies investigate the role of transforming growth factor-beta 1, a potent
      inhibitor of epithelial cell proliferation and stimulator of extracellular matrix
      biosynthesis, during intrahepatic bile duct hyperplasia and biliary fibrosis.
      These pathogenic responses were induced in rats by common bile duct ligation.
      Bile duct cell replication, measured by the bromodeoxyuridine labeling index, was
      significantly increased 24 hr after common bile duct ligation. This response
      diminished to baseline by 1 wk. Liver collagen content, determined by
      quantification of hydroxyproline, was increased significantly after 1 wk of
      common bile duct ligation, and by 4 wk was increased by a factor of 4.
      Immunohistochemistry revealed low levels of TGF-beta 1 in normal intrahepatic
      bile duct epithelium. In contrast, the bile duct epithelium in bile duct-ligated
      rats stained strongly positive for transforming growth factor-beta 1 at 1 and 4
      wk after ligation. These results suggest that transforming growth factor-beta 1
      may play a role in both the termination of the bile duct epithelial cell
      proliferative response and the induction of fibrogenesis after common bile duct
      ligation. In addition, the mannose 6-phosphate/insulin-like growth factor II
      receptor was up-regulated in hyperplastic bile duct epithelium 1 and 4 wk after
      ligation. Because the mannose 6-phosphate/insulin-like growth factor-II receptor
      has been shown to facilitate the proteolytic activation of transforming growth
      factor-beta 1, these results suggest that the bile duct epithelium may also be
      involved in the activation of transforming growth factor-beta 1.

PMID- 8294099
TI  - Protective effect of the lazaroid U74006F in cold ischemia-reperfusion injury of
      the liver.
AB  - Lipid peroxidation may play a major role in the loss of liver graft viability
      after prolonged cold ischemia and reperfusion injury. The lazaroid compound
      U74006F is a potent inhibitor of lipid peroxidation, and this study was designed
      to evaluate the efficacy of this compound in preventing cold ischemia-reperfusion
      damage in three different models: pig endothelial cells in culture, ex vivo
      isolated pig liver perfusion and orthotopic transplantation of syngeneic rat
      livers. The addition of U74006F to University of Wisconsin preservation solution
      significantly prolonged endothelial cell viability after 48 and 72 hr of cold
      ischemia and reoxygenation (p < 0.01). Donor pigs were injected with vehicle or
      U74006F (4.5 mg/kg) before liver harvest. After 24 hr of cold storage in
      University of Wisconsin solution, the livers were perfused with pig blood for 180
      min in an isolation chamber. Measurements of liver function parameters, including
      AST, ALT, bile production, superoxide anion and phospholipase A2 release, were
      assessed every 60 min. Although bile production was similar in the U74006F
      treated and control groups, significant decreases of AST and ALT levels (p <
      0.01) in the perfusate of the livers from treated donors were observed. In
      addition, the U74006F group displayed significantly reduced release of superoxide
      anion and phospholipase A2 compared with these parameters in the untreated group
      (p < 0.05 and p < 0.01, respectively). In the last model, donor rats were treated
      with U74006F before harvest; the rat liver grafts were preserved in cold
      University of Wisconsin solution for 24 hr and then transplanted into recipient
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294100
TI  - Modulation of the asialoglycoprotein receptor in human hepatoma cells: effect of
      glucose.
AB  - The hepatic receptor for asialoglycoproteins was found to be modulated by the
      glucose concentration in the medium of the human hepatoma cell line HepG2. The
      surface binding of asialoorosomucoid, a well-documented ligand for this receptor,
      increased from 20 ng/mg of cellular protein to about 40 ng/mg as the glucose
      concentration was increased from 10 to 50 mg/dl. The up-modulating effect of
      glucose was mimicked by pyruvate, a product of glucose metabolism, and abolished
      by both 2-deoxyglucose, an inhibitor of glucose metabolism, and by cycloheximide,
      an inhibitor of protein synthesis. Scatchard plot analysis indicated a rise in
      the number of binding sites and a twofold increase in binding affinity. In
      contrast, the binding of antibody remained unchanged with respect to alterations
      in glucose concentration, an indication that the actual number of receptors
      remained constant in face of an increased number of binding sites. Specificity of
      the glucose effect was shown by the binding of insulin and transferrin to their
      respective receptors, which was unaffected by the high glucose concentration that
      increased asialoorosomucoid binding. The repression of receptor binding seen with
      cells grown in biotin-deprived medium was reversed by increasing the glucose
      concentration of the medium. In this case, binding was restored to a level
      sixfold to sevenfold higher than that of the control cells grown in dialyzed
      serum. The stimulatory effect of glucose was shown to be independent of and
      significantly greater than that of cyclic GMP, a known regulator of receptor
      expression of biotin-deficient HepG2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294101
TI  - Regenerative changes in C/EBP alpha and C/EBP beta expression modulate binding to
      the C/EBP site in the c-fos promoter.
AB  - CCAAT/enhancer binding proteins are a family of basic zipper DNA binding proteins
      that regulate transcription of several liver-specific genes and certain growth
      related genes. Growth-related variations in the nuclear expression of one or more
      of the CCAAT/enhancer binding proteins may regulate the transition from the
      nonproliferative, differentiated phenotype of adult liver to the proliferative
      phenotype of regenerating liver. To evaluate this possibility, we used Northern-
      and Western-blot analyses to profile the expression of selected CCAAT/enhancer
      binding proteins in regenerating liver. Variations in CCAAT/enhancer binding
      protein expression were then correlated with changes in binding to the
      CCAAT/enhancer binding protein site of the c-fos promoter. Expression of both
      CCAAT/enhancer binding protein alpha and CCAAT/enhancer binding protein beta
      increases after partial hepatectomy. Steady-state levels of CCAAT/enhancer
      binding protein alpha mRNA increase 30% within an hour of partial hepatectomy (p
      < 0.05). This is followed by a transient increase in nuclear levels of
      CCAAT/enhancer binding protein alpha protein at 3 hr after partial hepatectomy (p
      = 0.08). In contrast, increases in CCAAT/enhancer binding protein beta mRNA and
      protein are more sustained. Levels of CCAAT/enhancer binding protein beta mRNA
      increase 400% to 500% within an hour of partial hepatectomy and remain increased
      throughout most of the prereplicative period (p < 0.01). Nuclear levels of
      CCAAT/enhancer binding protein beta protein are 200% to 300% greater than
      prehepatectomy levels at 3 hr (p < 0.001) to 6 hr (p < 0.05) and do not approach
      basal levels until 24 hr after partial hepatectomy. Gel mobility shift assays of
      nuclear extracts from regenerating livers indicate that these increases in
      nuclear protein expression are associated with increased DNA binding of
      CCAAT/enhancer binding protein alpha-beta heterodimers and beta-beta homodimers.
      These results demonstrate growth-related variations in the expression and DNA
      binding of both CCAAT/enhancer binding protein alpha and beta during liver
      regeneration and support the theory that altered CCAAT/enhancer binding protein
      DNA binding may contribute to regeneration-associated changes in liver cell
      phenotype.

PMID- 8294102
TI  - Effects of bile duct ligation on calcium excretion in the rat.
AB  - In an earlier study we showed that bile duct-ligated rats were highly susceptible
      to gentamicin nephrotoxicity and that oral calcium administration had a
      pronounced protective effect. The mechanism by which this occurs is unclear.
      Because cations compete with gentamicin for tubule binding sites, it has been
      suggested that the increased susceptibility of the kidney to gentamicin after
      bile duct ligation might result from decreased cation excretion. The aim of this
      study was to determine the effect of bile duct ligation on calcium excretion in
      relation to overall renal function. Male Sprague-Dawley rats underwent bile duct
      ligation and division. Pair-fed sham-operated rats served as controls. Metabolic
      and clearance studies were carried out at 3, 5, 7, 14 and 21 days after surgery.
      Urine output was higher in bile duct-ligated rats, and they excreted more calcium
      at 3, 5, 7 and 14 days, while excreting less sodium than controls. We conclude
      that after bile duct ligation, there is increased calcium excretion, which is
      independent of the abnormality in sodium excretion. Enhanced nephrotoxicity with
      aminoglycosides in the bile duct-ligated rat model cannot be explained by
      decreased calcium excretion.

PMID- 8294103
TI  - Modulation of hepatic sinusoidal endothelial cell function by Kupffer cells: an
      example of intercellular communication in the liver.
AB  - We tested the hypothesis that Kupffer cells modulate sinusoidal endothelial cell
      function in the liver. Rats were treated with Kupffer cell-depleting agents
      (gadolinium chloride and liposome-encapsulated dichloromethylene diphosphonate)
      or with inhibitors of phospholipase A2 or leukotriene A4 synthase (dexamethasone
      and diethylcarbamazine, respectively). Hyaluronan uptake by the isolated,
      perfused liver was measured as an index of the functional state of the sinusoidal
      endothelial cell. Plasma hyaluronan concentration was also determined. Three
      hours after Escherichia coli lipopolysaccharide administration (100
      micrograms/100 gm body wt, intravenously) plasma hyaluronan levels were
      significantly increased (280% to 320%), whereas hepatic hyaluronan uptake was
      markedly decreased (approximately 76%). Pretreatment with gadolinium chloride
      (0.5 mg/100 gm body wt, intravenously, 21 hr before saline solution or
      lipopolysaccharide administration), liposome-encapsulated dichloromethylene
      diphosphonate (40 mumol/100 gm body wt, intravenously, 44 hr before saline
      solution or lipopolysaccharide injection), dexamethasone (40 micrograms/100 gm
      body wt, intravenously, 1 hr before saline solution or lipopolysaccharide
      administration) or diethylcarbamazine (repeated doses, 10 mg/100 gm body wt,
      intravenously, 1 hr before saline solution or lipopolysaccharide injection)
      counteracted the lipopolysaccharide inhibitory effect on hepatic hyaluronan
      uptake. With the exception of gadolinium chloride, all other agents also
      prevented the lipopolysaccharide-induced increase in plasma hyaluronan
      concentration. Gadolinium chloride only attenuated the lipopolysaccharide effect
      on plasma hyaluronan level. Taken together with earlier results from our
      laboratory, these data indicate that: (a) Kupffer cell activation by
      lipopolysaccharide results in suppression of hyaluronan uptake by sinusoidal
      endothelial cells and (b) such modulation of endothelial cell function is likely
      mediated by products of the lipoxygenase pathway of arachidonate metabolism.

PMID- 8294104
TI  - Endotoxin-induced cytokine gene expression and excretion in the liver.
AB  - Peptide mediators, including tumor necrosis factor-alpha, interleukin 1 and
      interleukin-6, are associated with many chronic inflammatory diseases and septic
      shock. As such, considerable information has been collected by means of study of
      cytokine secretion from isolated cells or plasma cytokines during septic shock or
      inflammatory disorders. In this investigation, we used semiquantitative
      polymerase chain reaction analysis and a recently developed liver slice model to
      examine the characteristics of cytokine profiles that occur in the liver, the
      main organ involved in endotoxemia, after lipopolysaccharide challenge. Tumor
      necrosis factor-alpha, interleukin-1 alpha and interleukin-6 were rapidly
      secreted after in vivo LPS exposure or when added in vitro to rodent or human
      liver slice samples. This increase was associated with increased cytokine
      specific mRNA transcripts. Kinetic analysis revealed that most tumor necrosis
      factor-alpha is released from the liver within 1 hr of lipopolysaccharide
      challenge, whereas interleukin-1 alpha and interleukin-6 continued to be produced
      for the entire culture period. Addition of monoclonal antibodies against tumor
      necrosis factor-alpha or interleukin-1 alpha to the culture partly inhibited
      interleukin-6 secretion, indicating that interleukin-1 alpha and tumor necrosis
      factor-alpha help mediate and sustain interleukin-6 synthesis. Depletion of
      hepatic sinusoidal macrophages (Kupffer cells) by a liposome-mediated macrophage
      "suicide" technique indicated that almost all of the secreted interleukin-1 alpha
      and tumor necrosis factor-alpha originate from these cells, whereas interleukin-6
      secretion might also include other cell types. This study supports and extends
      previous findings and allows for a more rational approach to developing effective
      therapies against chronic inflammatory diseases and septic shock.

PMID- 8294105
TI  - In vivo response of hepatocytes to growth factors requires an initial priming
      stimulus.
AB  - Although growth factor effects have been studied in cultured hepatocytes, little
      information exists as to whether these factors can trigger hepatocyte replication
      in vivo. In this study we infused epidermal growth factor, transforming growth
      factor-alpha and hepatocyte growth factor directly into the portal vein of rats
      for 24 hr to see whether they could induce DNA synthesis in normal livers or in
      livers subjected to one-third hepatectomy. Infusion of transforming growth factor
      alpha or epidermal growth factor at doses up to 80 micrograms/24 hr had little
      effect on hepatic DNA synthesis in normal liver, whereas the monomeric and
      heterodimeric forms of hepatocyte growth factor generally produced increases of
      less than threefold in hepatic DNA synthesis. In contrast, after one-third
      hepatectomy infusion of epidermal growth factor, transforming growth factor-alpha
      or hepatocyte growth factor produced dose-dependent increases in hepatic DNA
      synthesis. At a dose of 40 micrograms/24 hr, epidermal growth factor increased
      DNA synthesis threefold, whereas transforming growth factor-alpha or hepatocyte
      growth factor increased DNA synthesis to greater than six times that in rats that
      had undergone hepatectomy alone. Furthermore, infusion of these growth factors,
      with or without one third-hepatectomy, induced the expression of transforming
      growth factor-alpha mRNA in the liver. The pattern of protooncogene expression
      induced by one-third hepatectomy was studied to determine the effect of this
      procedure in sensitizing the liver to the growth factors. Compared with the well
      characterized two-thirds hepatectomy system, there was a similar but smaller
      increase in c-myc expression but no induction of c-jun expression.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8294106
TI  - Acetaldehyde activates the promoter of the mouse alpha 2(I) collagen gene.
AB  - The mechanism whereby ethanol ingestion results in hepatic fibrosis remains
      unknown. Acetaldehyde has been shown to increase alpha 1(I) collagen gene
      transcription in human fibroblasts and in rat myofibroblastlike cells (Ito cells)
      in culture. In this study, the effect of acetaldehyde was determined on the
      activation of the alpha 2(I) collagen promoter. A plasmid containing the mouse
      alpha 2(I) collagen promoter region (-2000 to 54), fused to the coding sequence
      of the reporter gene chloramphenicol acetyl transferase and similar plasmid
      constructs containing deletions in the collagen promoter, were transfected into
      NIH 3T3 fibroblasts in culture. Acetaldehyde (200 mumol/L) and transforming
      growth factor-beta 1 (5 ng/ml) activated the wild type promoter. The combination
      of acetaldehyde and transforming growth factor-beta 1 did not result in a greater
      effect than either alone. Acetaldehyde inhibited, whereas transforming growth
      factor-beta 1 did not activate, the promoter, with a -352 to -104 deletion. By
      contrast, acetaldehyde had no effect, whereas transforming growth factor-beta 1
      resulted in a small decrease in the activity of the promoter, with a -501 to -352
      deletion. This study shows that acetaldehyde and transforming growth factor-beta
      1 independently activate the mouse alpha 2(I) collagen promoter and that this
      activation is mediated by the same proximal region of the promoter.

PMID- 8294107
TI  - Pathways of intracellular trafficking and release of ferritin by the liver in
      vivo: the effect of chloroquine and cytochalasin D.
AB  - We have previously shown that the clearance of exogenous ferritin and the release
      of endogenous ferritin into both serum and bile are altered by the microtubular
      inhibitor colchicine. In this study we further examined the role of the lysosome
      endosome pathway in ferritin metabolism. We examined the effect of the
      lysosomotropic agent chloroquine and the microtubular inhibitor cytochalasin D on
      the uptake and release of ferritin by normal and iron-loaded rats under basal
      conditions and in the presence of an exogenous tissue ferritin load. Either
      chloroquine (50 mg/kg body wt) or cytochalasin D (0.9 microgram/100 gm body
      wt/min) was administered to normal and iron-loaded rats at zero time. Rats were
      also infused with either saline solution or rat liver ferritin containing a trace
      amount of 125I-ferritin. The clearance of 125I-ferritin from the circulation was
      not affected by chloroquine or cytochalasin D either in normal or in iron-loaded
      rats; however, both chloroquine and cytochalasin D decreased the serum ferritin
      concentration in normal rats to 39% +/- 9% and 22% +/- 7% of the baseline serum
      ferritin levels, respectively, implying that both drugs inhibited the release of
      endogenous ferritin in normal rats. In iron-loaded rats both chloroquine and
      cytochalasin D decreased the biliary ferritin concentration to 11% +/- 1% and 37%
      +/- 4% of the baseline ferritin levels, respectively, and the 125I protein-bound
      counts per minute in the bile to 50% of the control result. This finding is
      consistent with an inhibitory effect of both drugs on the biliary excretion of
      endogenous ferritin and the intracellular transport of exogenous ferritin,
      respectively. In the presence of an exogenous tissue ferritin load, there was no
      detectable inhibitory effect of either drug on the biliary excretion of either
      endogenous or exogenous ferritin. These results provide the following evidence:
      (a) the receptor-mediated endocytosis of ferritin is not dependent on functioning
      lysosomes or microfilaments; (b) the release of endogenous ferritin into the
      serum of normal rats and the bile of iron-loaded rats is a chloroquine-sensitive,
      microfilament-dependent process; (c) the biliary excretion of trace amounts of
      exogenous ferritin is dependent on both chloroquine-sensitive vesicles and
      microfilaments; and (d) increased levels of exogenous ferritin are excreted
      directly into the bile by way of a second microfilament-independent, chloroquine
      insensitive pathway. This study provides support for a physiological mechanism
      for the release of ferritin from the liver.

PMID- 8294108
TI  - Spontaneous Ca2+ release from a caffeine and ryanodine-sensitive intracellular
      Ca2+ store in freshly prepared hepatocytes.
AB  - A considerable fraction of freshly prepared hepatocytes loaded with the
      fluorescent [Ca2+]i indicator fura-2 exhibited spontaneous rhythmic fluctuations
      that tended to decrease with increasing length of incubation after isolation.
      These oscillations were dependent on the external Ca2+. They could no longer be
      observed when a Ca2+ chelator-(ethylenebis [oxyethylenenitrilo]) tetraacetic acid
      -was added to medium. Addition of thapsigargin, which is known to release Ca2+
      from inositol 1,4,5-trisphosphate-sensitive and -insensitive Ca2+ stores, induced
      a large transient increase in [Ca2+]i and abolished the fluctuations. When the
      cells were treated with 2 mmol/L caffeine, frequency was increased, whereas 10
      mmol/L caffeine induced a single large peak followed by a persistent plateau.
      Moreover, addition of dibutyryl cAMP led to decreased frequency of fluctuations.
      Ryanodine caused larger fluctuations; thereafter the [Ca2+]i level became much
      higher and the spikes ceased. These results suggest that spontaneous rhythmic
      fluctuations in freshly prepared hepatocytes are driven by Ca2+ release from a
      caffeine- and ryanodine-sensitive calcium-induced calcium release pool.

PMID- 8294109
TI  - Nutritional supplementation in chronic liver disease: an analytical review.

PMID- 8294110
TI  - End-stage liver disease in a young woman.

PMID- 8294111
TI  - Transgenic mouse models of hepatocellular carcinoma.

PMID- 8294112
TI  - Liver GLUT-1 expression: an enigma deepens.

PMID- 8294113
TI  - . . . and the bands play on. Variceal banding ligation versus injection
      sclerotherapy for bleeding oesophageal varices.

PMID- 8294114
TI  - Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis: an
      analysis of the serological marker CA 19-9.

PMID- 8294115
TI  - Effect of androgen treatment on fear reactions in ewes.
AB  - The effects of prolonged androgen treatment (testosterone propionate, 10 mg/day
      for 56 days) on fear reactions in ewes were studied using a battery of tests
      previously designed and validated. These tests involved situations classically
      reported to induce fear in sheep: isolation from conspecifics, surprise, and
      presence of a human. Testosterone-treated ewes differed from controls in a number
      of behavioral characteristics which indicate that they are less fearful in the
      various test situations. Their overall scores were respectively 9.5 vs 11.5 (P <
      0.05) in the isolation test, 7.9 vs 13.1 (P < 0.001) in the surprise test, and
      7.8 vs 13.2 (P < 0.001) in the human test. Testosterone treatment thus clearly
      reduces fear reactions in ewes subjected to nonsocial situations that are
      typically fear-eliciting.

PMID- 8294116
TI  - Hormonal modulation of the cutaneous initiation of lordosis in infant and adult
      rats.
AB  - The purpose of these experiments is to compare the regional specificity
      (Experiment 1) and the hormonal modulation (Experiment 2) of the cutaneous
      initiation of lordosis in 4- to 6-day-old male and female rats (infants) and in
      60- to 90-day-old female rats (adults). In Experiment 1, subjects were primed
      with 100 micrograms estradiol benzoate (EB) and 0.5 mg progesterone (P) and were
      denervated on the Waist (dermatomes L1-L3), Midriff (dermatomes T10-L3), Flanks
      (dermatomes L4-L6), or Sides (dermatomes T10-L6). In infants, there were no
      significant differences between males and females. Denervation of the Waist,
      Midriff, or Sides but not of the Flanks significantly decreased the percentage of
      subjects displaying lordosis, lordosis quotient (LQ), and mean lordosis duration;
      no significant differences were obtained among Waist-, Midriff, or Sides
      denervated infants. In contrast, denervation of the Sides but not of the Waist
      significantly decreased LQ and mean lordosis intensity among adults. In
      Experiment 2, Waist-denervated infants and their surgical Controls were treated
      either with 100 micrograms EB and 0.5 mg P or with the oil vehicle; Waist
      denervated adults and their surgical Controls received either 100 or 10
      micrograms EB (no P). Regardless of hormone treatment, denervation of the Waist
      significantly decreased LQ and lordosis duration in infants and decreased LQ and
      lordosis intensity in adults. In infants, the only effect of priming with EB and
      P was to increase the percentage of pups showing lordosis and lordosis duration
      among the surgical Controls. In contrast, priming with 100 micrograms EB
      significantly increased the percentage of rats displaying lordosis, LQ, and
      lordosis intensity among Waist-denervated adults. These data suggest that
      cutaneous input from the Waist is important for eliciting lordosis in both infant
      and adult rats, and that the importance of this input is modulated by hormone
      priming in adult but not infant rats.

PMID- 8294117
TI  - Endocrine changes associated with spawning behavior in male kokanee salmon
      (Oncorhynchus nerka) and the effects of anosmia.
AB  - This study examines the relationship between social status, behavioral activity,
      and hormone levels through the spawning cycle in male kokanee salmon
      (Oncorhynchus nerka). Shortly after arrival at the spawning grounds, male kokanee
      undergo dramatic changes in morphological and physiological condition: there is
      an increase in body depth, a bright silvery appearance is replaced by an intense
      red coloration, and spermiation commences. Males become associated with nesting
      females which they defend against other males. The androgens, testosterone and 11
      ketotestosterone, decline slowly over the spawning period from high levels
      observed in the silvery males; gonadotropin (GtH II) and 17 alpha, 20 beta
      dihydroxy-4-pregnen-3-one increase as males approach final maturation. Androgen
      and GtH levels in males placed in pens with females over the spawning bed were
      higher than those in males penned without females. Among males competing for
      females, amounts of milt and plasma concentrations of GtH were higher in those
      males that were successful in gaining access to nesting females. A marked
      reduction in milt and plasma hormones following cauterization of the olfactory
      nares indicates that olfactory stimuli play a role in mediating endocrine and
      spermiation responses to the nesting females. Anosmic males were less vigorous
      and persistent in their courtship, suggesting that, either a female pheromone
      and/or high levels of hormone are necessary to maintain full reproductive
      behavior in male kokanee. The role of socially induced hormone changes in
      modulating reproductive behavior is discussed.

PMID- 8294118
TI  - Facilitation of sexual receptivity by ventromedial hypothalamic implants of the
      antiprogestin RU 486.
AB  - RU 486 is known primarily as an antagonist to progestins and glucocorticoids.
      However, RU 486 has also been shown to have agonistic progestational properties
      in biochemical and behavioral studies. In the current study, RU 486 was implanted
      directly into the ventromedial hypothalamus (VMH) to test for facilitative action
      on the receptive behavior of female ovariectomized Long-Evans rats primed with 5
      micrograms of estradiol benzoate. Cannulae containing RU 486, progesterone (P),
      or empty cannulae were implanted 48 hr after estrogen priming. The lordosis
      quotient and the lordosis score were assessed 4 hr after the cannulae were
      lowered by a standardized test consisting of 10 mounts by a stimulus male. P and
      RU 486 significantly facilitated receptivity compared to blank implants in terms
      of lordosis quotient and lordosis score, with no significant difference between
      the hormone treatments. While only a single dose of each treatment was given in
      the current study, RU 486 facilitated lordosis when implanted to the VMH as well
      as progesterone in contrast to our previous results where the steroids were
      administered systemically.

PMID- 8294119
TI  - Hormonal induction of male courtship behavior in the Japanese newt, Cynops
      pyrrhogaster.
AB  - In the breeding season, the sexually mature male newt, Cynops pyrrhogaster,
      vibrates the tail in front of the female at an early stage of courtship. Effects
      of prolactin (PRL), gonadotropin (GTH), and sex steroids on this behavior were
      investigated in the male paired with the female receiving PRL and GTH. The
      behavior was elicited in the sexually inert male by injections of PRL of bovine,
      ovine, or bullfrog origin and human chorionic gonadotropin or bullfrog LH and FSH
      in combination. The effect of PRL or GTH alone was less marked than that of PRL
      plus GTH, especially in terms of frequency of the behavior. In the
      hypophysectomized male, combination of PRL and GTH significantly increased both
      the incidence and frequency of the behavior. However, PRL alone was not
      effective, and the effect of GTH alone was less pronounced than that in the
      intact animal receiving GTH injections. The effect of GTH was nullified by
      castration. In the PRL-treated castrated animal, testosterone or
      dihydrotestosterone, but not estradiol, was effective in inducing the behavior.

PMID- 8294120
TI  - Roles of gonadal hormones in control of five sexually attractive odors of meadow
      voles (Microtus pennsylvanicus).
AB  - The role of gonadal hormones in the production of five odors that are attractive
      to the opposite sex was investigated in meadow voles, Microtus pennsylvanicus.
      Preferences of intact male and female voles for the scents of same- versus
      opposite-sex conspecifics were examined. The attractiveness of opposite-sex
      scents from feces, mouth, and the posterolateral region was eliminated by
      gonadectomy of scent donors and was restored by replacement with testosterone in
      male donors and estradiol-17 beta in female donors. The attractiveness of the
      scents of urine and the anogenital area was reduced by gonadectomy of scent
      donors, but was not eliminated. This suggests that the sexually attractive
      components of urine and the anogenital area do not depend solely on gonadal
      hormones. The present data suggest that (1) gonadal hormones have an important
      role in production of sexually attractive components of all scents that we found
      to be sexually distinctive, but (2) the sexually attractive components of some
      scents are in addition influenced by other factors, possibly other hormones.
      Nongonadal influences on these scents may provide sexually distinctive
      information outside the breeding season when endogenous gonadal hormone
      concentrations are low.

PMID- 8294121
TI  - Brood size affects behavior, interclutch interval, LH levels, and weight in ring
      dove (Streptopelia risoria) breeding pairs.
AB  - This study examines the effects of experimental manipulation of brood size (one
      or two squabs) on the behavior, interclutch interval, plasma LH concentrations,
      and weights of ring dove parents. Twelve dove pairs were observed, sampled, and
      weighed over a cycle with one and a cycle with two squabs. Before hatch, no
      parameter showed any difference between pairs which would subsequently have one
      or have two squabs. After hatch, males and females having one squab fed less,
      while males showed more perch-, bow-, and nest-cooing over the 2 weeks after
      hatch. Females also showed more nest-cooing with one squab and a shorter
      interclutch interval. For both sexes the plasma LH concentrations were higher
      when rearing a single squab, showed a lesser decrease after hatch, and increased
      more rapidly. Both sexes also showed a smaller weight loss when rearing a single
      squab. The results show that the intricate relationships between behavior,
      physiology, and reproduction in the ring dove are tuned to brood size and
      emphasize the latter factor as an important and meaningful variable in the doves'
      reproductive cycle.

PMID- 8294122
TI  - Neonatal testicular suppression with a GnRH agonist in rhesus monkeys: effects on
      adult endocrine function and behavior.
AB  - Male rhesus monkeys secrete adult levels of androgen for 3 months postnatally.
      The role of this neonatal testicular secretion in sexual development was
      investigated by suppressing luteinizing hormone (LH) and testosterone (T) in
      neonatal male rhesus (n = 6) by administering a gonadotropin-releasing hormone
      agonist (Ag) for the first 4 months of postnatal life. Controls (n = 4) received
      vehicle. Six years later, endocrine function and sexual behavior were examined
      with ovariectomized females (n = 6) receiving periodic estradiol (E2) treatment
      during the breeding and nonbreeding seasons. During the breeding season, there
      were no differences between Ag-treated and control males in levels of LH and T or
      in frequency of copulatory behavior. However, Ag-treated males masturbated less
      frequently than controls when the females were not on E2. During the nonbreeding
      season, Ag-treated males had lower T levels than controls when the females were
      not receiving E2 and copulated less when the females received E2, even though T
      levels were comparable. During both E2 and non-E2 treatments, Ag-treated males
      secreted less T per unit of LH than controls. Neonatal Ag treatment had no effect
      on social rank. These data demonstrate that neonatal testicular suppression, or
      the Ag treatment itself, altered systems regulating sexual motivation and
      neuroendocrine control of these males and suggest that the early neonatal period
      in male rhesus monkeys is another point when the developing central nervous
      system is sensitive to the organizing actions of androgens.

PMID- 8294123
TI  - Treatment with an anabolic-androgenic steroid affects anxiety-related behavior
      and alters the sensitivity of cortical GABAA receptors in the rat.
AB  - The putative psychotropic effect of the anabolic-androgenic steroid, testosterone
      propionate (TP), was determined in intact adult male rats after 1 or 2 weeks of
      continued exposure via subcutaneously implanted capsules. Behavior was assessed
      in a novel open-field arena and in the elevated plus-maze. In addition, gamma
      aminobutyric acid (GABA)-stimulated 36chloride (Cl-) influx was determined in
      cerebral cortical synaptoneurosomes as a function of TP exposure. The weight of
      the prostate gland was taken and blood serum level of total testosterone (T) was
      assayed. One week of TP exposure (approximately 3.5-5.0 mg/kg per day) resulted
      in anxiolytic behavior, as evidenced by an increase in the exploration of the
      open arms of the elevated plus-maze. The behavioral effect in the elevated plus
      maze was not observed in animals exposed to TP for a 2-week period. Ambulation
      scores in the novel open field did not change as a function of TP exposure. Blood
      T levels were increased 7-fold by 1 week of exposure, and increased 10-fold in
      animals with implants for a 2-week period. After 1 week of TP exposure, the
      concentration of GABA that elicited 50% of the maximal Cl- influx in cortical
      synaptoneurosomes (i.e., EC50) was significantly decreased; this effect was not
      seen in animals exposed to TP for 2 weeks. The maximal efficacy of the GABAA
      receptor-gated Cl- influx was not affected after 1 or 2 weeks of TP treatment.
      Thus, 1 week of treatment with TP resulted in anxiolytic behavior that was
      accompanied by an increase in the sensitivity of cortical GABAA receptors.
      However, the behavioral and neurochemical changes were no longer present after 2
      weeks of TP exposure. These results are discussed in terms of the agonist effects
      of reduced androgen metabolites at the GABAA receptor and the possible
      development of tolerance to these effects.

PMID- 8294124
TI  - A linear time-varying model of force generation in skeletal muscle.
AB  - A model of isometric force production by skeletal muscle was developed in which
      the response to each stimulus in a train was described by a critically damped,
      linear second-order system. The parameters describing the system were constrained
      to be constant within an interstimulus interval, but were allowed to vary between
      interstimulus intervals. The ability of this model to match experimental data,
      and the time variation in the parameters (low-frequency gain and natural
      frequency) required to do so were examined in soleus and plantaris muscles of the
      cat stimulated by synchronous whole-nerve stimulation. The model produced good
      fits across firing rates from twitch to tetanus for slow and fast muscle, rested
      and fatigued muscle, and maximal submaximal stimulation. Both gain and natural
      frequency generally varied smoothly and predictably under all conditions. Gain
      increased at intermediate stimulation rates and in potentiated muscle, and
      decreased with fatigue and submaximal stimulation. Natural frequency was higher
      in fast muscle, and decreased with stimulation rate and fatigue. This modeling
      approach may provide a useful alternative to current models of skeletal muscle
      force, as its implementation is simple and it can describe force under conditions
      (fatigue, potentiation) where the muscle dynamics change with time.

PMID- 8294125
TI  - Stability and control of a frontal four-link biped system.
AB  - A conceptual model for studying the involvement of the central nervous system
      (CNS) in the performance of lateral swaying movements is described. The model is
      based on a four-link planar biped that approximates gross human locomotion in the
      frontal plane. The viscoelastic function of the musculoskeletal system provides a
      linear controller for the system. Such an intrinsic controller can effectively
      duplicate simple well-learned tasks in the absence of higher level CNS feedback.
      This hypothesis is supported by comparing the proposed controller with two
      neurophysiologically involved linear decoupling schemes. Reference trajectories
      for swaying commands are recorded from experiments conducted in the Gait Analysis
      Laboratory of the Ohio State University Hospitals. These reference trajectories
      are inputs to all three controllers. The viability of intrinsic feedback scheme
      in the execution of swaying tasks is demonstrated via comparison of responses
      from the three controllers.

PMID- 8294126
TI  - Fatigue compensation of the electromyographic signal for prosthetic control and
      force estimation.
AB  - During a sustained muscle contraction, the amplitude of electromyographic (EMG)
      signals increases and the spectrum of the EMG signal shifts toward lower
      frequencies. These effects are due to muscular fatigue and can cause problems in
      the control of myoelectric prostheses and in the estimation of contraction level
      from the EMG signal. It has been well known that the fatigue effects can be
      explained by the conduction velocity changes during the fatigue process and by
      the idea that the conduction velocity is linearly proportional to the median
      frequency of EMG signals. Hence the fatigue process can be monitored by measuring
      the median frequency. A fatigue compensation preprocessor has been developed. It
      uses the widely accepted power spectrum density model of EMG signals that
      contains the conduction velocity as a measure of fatigue. It was verified that
      the preprocessor scales down the amplitude of the fatigued EMG signal and
      decompresses the spectrum. Hence, the preprocessor eliminates the increase in
      amplitude and the shift in frequency and enables consistent EMG signals to be
      used to control prostheses.

PMID- 8294127
TI  - Sensory nerve recording for closed-loop control to restore motor functions.
AB  - A method is developed for using neural recordings to control functional
      electrical stimulation (FES) to nerves and muscles. Experiments were done in
      chronic cats with a goal of designing a rule-based controller to generate
      rhythmic movements of the ankle joint during treadmill locomotion. Neural signals
      from the tibial and superficial peroneal nerves were recorded with cuff
      electrodes and processed simultaneously with muscular signals from ankle flexors
      and extensors in the cat's hind limb. Cuff electrodes are an effective method for
      long-term chronic recording in peripheral nerves without causing discomfort or
      damage to the nerve. For real-time operation we designed a low-noise amplifier
      with a blanking circuit to minimize stimulation artifacts. We used threshold
      detection to design a simple rule-based control and compared its output to the
      pattern determined using adaptive neural networks. Both the threshold detection
      and adaptive networks are robust enough to accommodate the variability in neural
      recordings. The adaptive logic network used for this study is effective in
      mapping transfer functions and therefore applicable for determination of gait
      invariants to be used for closed-loop control in an FES system. Simple rule-bases
      will probably be chosen for initial applications to human patients. However, more
      complex FES applications require more complex rule-bases and better mapping of
      continuous neural recordings and muscular activity. Adaptive neural networks have
      promise for these more complex applications.

PMID- 8294128
TI  - Quantitative in vivo measurements of inner ear tissue resistivities: I. In vitro
      characterization.
AB  - An in vivo resistivity measurement system, based on the four-electrode reflection
      coefficient technique that nondestructively measures the complex resistivity of
      cochlear tissues, is described. Details of the theory and instrumentation used
      for noninvasive measurement of resistivity are presented. In vitro experiments
      both characterize the accuracy of the proposed resistivity measurement system and
      establish general criteria for ensuring that a particular theoretical model
      accurately represents the experimentally measured geometry. Two idealized
      geometries (two-layer planar and two-layer spherical) are measured
      experimentally; error analyses using experimental results describe the maximum
      error with which the experimental system noninvasively estimates resistivity from
      experimental reflection coefficient measurements. The precise accuracy of a
      noninvasive resistivity estimate depends on both the variability for
      experimentally measuring the reflection coefficient of a particular geometry and
      the average value of the measured reflection coefficient. For example, two-point
      measurements of an in vitro two-layer planar interface allow noninvasive
      estimation of complex resistivity with total errors of less than 1%. In addition
      to characterizing accuracy of resistivity estimates for different in vitro
      geometries, two general criteria were established: 1) any inhomogeneity within
      13.3 times the average interelectrode separation (i.e., within 1662.5 microns for
      an interelectrode separation of 125 microns) from the microelectrode array must
      be included in the geometry of the theoretical model and 2) all inhomogeneous
      boundaries with a radius of curvature greater than 100 times the average
      interelectrode separation (i.e., greater than 12.5 mm for an average electrode
      separation of 125 microns) are accurately represented by a planar geometric
      model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294129
TI  - An alternative to the biomagnetic forward problem in a realistically shaped head
      model, the "weighted vertices".
AB  - The "weighted vertices" (WV), an alternative in solving the biomagnetic forward
      problem (BFP) for a realistically shaped head (RSH) model are presented. This
      proposed approach differs from the others in the way some terms in the governing
      integral equations are defined. The effects that WV has on important issues such
      as the "auto solid angle" and "stability of equations" are discussed. Two
      variants of the WV approach, i.e., the "linear weight" and the "quadratic
      weight," have been developed, and comparison of results produced by these two
      approaches shows that the implementation of quadratic elements to evaluate the
      integral produces significant improvements. This study is done with a focus on
      magnetic rather than electric phenomena, so a homogeneous conductor has been used
      in the numerical example. However, the thoughts behind this proposed method can
      be easily extended for cases where inhomogeneous conductors are involved.
      Significant improvement in the accuracy of the forward problem has been observed
      by use of the WV approach.

PMID- 8294130
TI  - Electric-field-induced volume and membrane ionic permeability changes of red
      blood cells.
AB  - When an external electric field (EF) is applied to red blood cells (RBC's), the
      RBC's are observed to undergo a swelling action. The swelling may or may not lead
      to hemolysis, depending on the EF strength. An objective verification of this
      swelling is by measuring the RBC mean corpuscular volume (MCV). In this study,
      the RBC's were exposed to the appropriate EF strength to induce swelling, but
      caused minimal hemolysis. The MCV was measured. The change in the erythrocyte
      membrane ionic permeability as a result of the EF exposure was also determined,
      as an objective verification of presumed membrane conductance change concomitant
      with the swelling. The fluxes of cations K+, Na+, and Ca++ and anion Cl- were
      measured. The results showed that red cell MCV was indeed increased after EF
      application. The EF also altered the membrane ionic conductance to allow ions to
      flow down their respective concentration gradient across the membrane. Without a
      counterbalancing ionic pressure gradient, hemoglobin colloidal pressure
      inevitably drew H2O in, thus producing the observed swelling.

PMID- 8294131
TI  - Efficient electrode spacing for examining spatial organization during ventricular
      fibrillation.
AB  - Spatial organization has been observed during episodes of ventricular
      fibrillation (VF) by recording epicardial unipolar electrograms on a grid of
      electrodes. In such studies, the choice of spacing between electrodes is an
      important decision, affecting the resolution and the size of the domain to be
      studied. A basic tenet of sampling theory, the Nyquist criterion, states that an
      electrode spacing smaller than half the smallest significant wavelength is
      required to capture the important details of a spatially sampled process. In this
      paper, we suggest a method to choose a practical interelectrode spacing by
      examining wavenumber power spectra of high-resolution VF data recorded from a
      square 11 x 11 array of electrodes spaced 0.28 mm apart. The plaque was sutured
      on the epicardium near the left ventricular apex in seven anesthetized pigs. VF
      was induced with ac simulation. Unipolar extracellular electrograms were
      simultaneously recorded from each channel for 2 s after the induction of VF. Each
      signal was sampled in time at 1000 Hz. Wavenumber power spectra were calculated
      for 100 ms segments using the zero-delay wavenumber spectrum method, for a total
      of 140 power spectra. All spectra had dominant peaks at the origin and fell off
      rapidly with increasing wavenumber (decreasing wavelength). In all the spectra,
      every wavelength shorter than 1.4 mm contributed insignificant power.
      Furthermore, in 134 of 140 spectra (96%), insignificant power levels were
      associated with every wavelength shorter than 2.8 mm. These results suggest that,
      for unipolar extracellular electrodes, an intersensor spacing on the order of 1
      mm is appropriate to study organization during early VF.

PMID- 8294132
TI  - Low-frequency Korotkoff signal analysis and application.
AB  - The low-frequency components of the Korotkoff signal are recorded, analyzed, and
      applied in the derivation of blood pressure estimates. The low-frequency
      components are found to be the dominant feature of the Korotkoff signal
      throughout the entire occlusive cuff deflation cycle, and a sharp rise in the
      energy of these components is found to correlate with the occurrence of systolic
      pressure. This feature is applied in two separate energy thresholding algorithms
      which produce estimates of systolic blood pressure which correlate well (r =
      0.907 and r = 0.938) with those systolic pressure derived via the auscultatory
      technique.

PMID- 8294133
TI  - Real-time left ventricular volume of the canine heart from ultrasonic dimension
      data.
AB  - A real-time (instantaneous) system is presented to measure the dynamic volume of
      the left ventricle. This system uses the invasive measurement of long axis
      diameter, short axis diameter, and wall thickness of the cardiac left ventricle.
      Three pairs of pulse-transit ultrasonic dimension transducers are used to obtain
      these measurements. The dynamic volume was then found by applying these
      measurements to an ellipsoidal shell model of the left ventricle. It is possible
      to obtain on-site, real-time, continuous measurements of the left ventricular
      volume (LVV) by employing an electronic device which implements a corrected
      volume equation for the ellipsoidal shell model. The device's output is a
      calibrated estimation for the LVV. The function of the device is shown to compare
      well with other accepted measurements for the LVV.

PMID- 8294134
TI  - Tracking of changes in latency and amplitude of the evoked potential by using
      adaptive LMS filters and exponential averagers.
AB  - The adaptive LMS algorithm in combination with exponential averagers are compared
      to the use of exponential averagers only in tracking latency and amplitude
      changes in the evoked potential. The estimator is intended for use in
      applications where neurologic functions are monitored by detecting changes in the
      evoked potential. Two different structures of the estimator are evaluated and it
      is found that averaging before filtering is to be preferred. It is shown that the
      desired signal to the LMS-filter can have a rather low SNR with only mirror
      influence on the estimator performance. The estimator which combines an LMS
      filter and an exponential averager was shown to detect changes in latency faster
      than the estimator which uses a nonfiltered average. The LMS-filter is shown to
      exhibit bias in the estimate of the evoked potential due to the fact that
      response and background spectra has overlapping frequency ranges. The bias seems
      not to affect the latency estimation while amplitude estimation was clearly
      affected. Simulations are performed with both white noise and EEG background.

PMID- 8294135
TI  - Power deposition properties of a travelling-wave applicator for interstitial
      hyperthermia.
AB  - An interstitial hyperthermia applicator is described that is capable of providing
      uniform heating over an extended range of depths. The applicator utilizes glossy
      two-wire transmission lines that are terminated in p-i-n diodes that may be
      biased on or off. A pair of these transmission lines within a single applicator
      allows a variety of symmetrical and asymmetrical patterns to be produced.
      Theoretical predictions of the applicator's performance are provided that are
      based on empirically determined transmission line characteristics.

PMID- 8294136
TI  - Algorithm to control "effect compartment" drug concentrations in pharmacokinetic
      model-driven drug delivery.
AB  - In most computer-controlled pharmacokinetic model-driven drug infusion pumps,
      simulation of a linear compartmental pharmacokinetic model is used to compute the
      rate of intravenous drug infusion required to achieve setpoint central
      compartment (plasma) drug concentrations. For many drugs, it has been suggested
      that it is the drug concentration in a hypothetical "effect" compartment, rather
      than in the plasma, that should be manipulated to achieve maximum control over
      pharmacologic action. Controlling the effect compartment drug concentration is
      algorithmically more difficult than controlling the central compartment drug
      concentration because of the time delay between administration of drug into the
      central compartment and its subsequent appearance in the effect compartment.
      Presented in this paper is a model-based dosing algorithm for use in
      pharmacokinetic model-driven drug infusion devices that target the theoretical
      effect compartment drug concentration.

PMID- 8294137
TI  - Serum-soluble CD4 as clinical and immunological marker in patients with dilated
      cardiomyopathy.
AB  - Serological markers of cell-mediated immunity, i.e., soluble CD4, soluble
      interleukin-2 (Il-2) receptor and beta 2-microglobulin, were determined in 60
      patients with dilated cardiomyopathy. Compared with normal healthy donors (n =
      30) and controls who had coronary artery disease with preserved left ventricular
      function (n = 20), significantly increased levels associated with the New York
      Heart Association functional classes have been found in the cardiomyopathy
      patients, irrespectively of the etiology. Out of the immunological variables
      tested, serum-soluble CD4 most closely reflected the clinical and hemodynamic
      stage, predicted the presence of lymphocytic aggregates in the myocardium and
      correlated with the CD4/CD8 ratios of endomyocardial lymphocytes (r = 0.6, P <
      0.05). Conversely, focal mononuclear infiltration of the myocardium was
      associated with significantly elevated CD4/CD8 ratios (2.1 +/- 0.6 vs. 1.3 +/-
      0.2, P < 0.05), higher total numbers and percentages of endomyocardial
      lymphocytes expressing the pan T-markers CD2 and CD3, more CD45RO/UCHL1-positive
      cells and more CD4-positive T-helper cells, compared with non-reactive cases the
      lymphocytes of which were scattered throughout the myocardium. In conclusion, in
      a subset of cardiomyopathy patients lymphocytic clusters in the myocardium
      indicated an enhanced cellular immune response predominantly mediated by CD4
      positive T-helper lymphocytes with active memory function. This
      immunopathological condition in the heart can be monitored by serum-soluble CD4.

PMID- 8294138
TI  - Activation of human monocyte/macrophage cytotoxicity by IL-2/IFN gamma is linked
      to increased expression of an antitumor receptor with specificity for acetylated
      mannose.
AB  - Spontaneous cytotoxicity of human monocytes (purity: 92-95%) against K562 tumor
      cells was only observed in 31% healthy donors but, in the presence of
      rhamnogalacturonan (500 ng/ml), enhanced cytotoxicity was recorded for 79% (n =
      14) of the donors. Monocytes activated by culturing with interleukin-2 and/or IFN
      gamma showed increased antitumor cytotoxicity against K562 tumor cells in 86% (n
      = 21) of the donors exhibiting additional increases in specific cytotoxicity when
      the cytotoxicity assays were carried out in the presence of rhamnogalacturonan.
      Increases of monocyte cytotoxicity achieved by activation with cytokines
      coincided with increased formation of monocyte/tumor cell conjugates. Similarly,
      increased monocyte cytotoxicity mediated by rhamnogalacturonan also correlated
      with increased monocyte/tumor cell conjugate formation most likely due to
      effector cell/target cell bridging as was originally described for
      rhamnogalacturonan interacting with CD56+ natural killer or lymphokine-activated
      killer cells and tumor cells. The chemospecificity of the monocyte-based
      receptors responsible for cytotoxicity and for monocyte/tumor cell conjugate
      formation, as well as for their rhamnogalacturonan-mediated enhancements, appears
      to be identical since all these effects could be inhibited in a dose-dependent
      manner by partially deacetylated (60%) mannose pentaacetate.

PMID- 8294139
TI  - V gamma gene usage in peripheral blood gamma delta T cells.
AB  - The majority (50-90%) of gamma delta T cells in the peripheral blood of adult
      individuals expresses a T-cell receptor (TCR) which uses V gamma 9 and V delta 2
      as variable elements. Little is known about the distribution of other V gamma
      gene elements in the remaining 10-50% of gamma delta T cells. Here we have
      studied the V gamma gene expression in peripheral blood gamma delta T cells by 3
      color flow cytometry analysis applying established monoclonal antibodies (mAb)
      directed against V gamma 9 and V gamma 4, as well as a novel mAb directed against
      V gamma 2, V gamma 3 and V gamma 4. On average, 79.9% of gamma delta T cells
      expressed V gamma 9, 11.9% V gamma 2/V gamma 3, 4.4% V gamma 4, and 7.5% one of
      the remaining V gamma 5, V gamma 8, V gamma 10 or V gamma 11 elements. There were
      remarkable variations in the gamma delta subset composition between individual
      donors. The majority (69.8%) of V gamma 2/V gamma 3/V gamma 4-bearing cells co
      expressed V delta 1, while on average only 17.8% of V gamma 2/V gamma 3/V gamma 4
      bearing cells co-expressed V delta 2. This is in contrast to V gamma 9-bearing
      gamma delta T cells, of which 83.1% used V delta 2 and only 12.7% V delta 1.
      Taken together, this data identifies V gamma 2/V gamma 3 as the second most
      frequently used set of V gamma elements in human peripheral blood gamma delta T
      cells.

PMID- 8294140
TI  - Beta-adrenergic receptors mediate in vivo the adrenaline inhibition of
      lipopolysaccharide-induced tumor necrosis factor release.
AB  - Adrenaline has been shown to inhibit the release of tumor necrosis factor (TNF)
      elicited by lipopolysaccharide (LPS) when tested in vitro on cultured human blood
      cells and rat macrophages. In this report we have examined the effect of the in
      vivo administration of adrenaline on TNF serum levels induced by LPS. In
      agreement with in vitro data, adrenaline (0.1 mg/kg, s.c.) was found to inhibit
      in the mouse the LPS-induced TNF release. The beta-adrenergic antagonist
      propranolol administered 1 h before adrenaline completely blocked the adrenaline
      activity, whereas the alpha-adrenergic antagonist phentolamine was ineffective.
      These data demonstrate that: (i) adrenaline is an effective antagonist of LPS
      induced TNF release in vivo, and (ii) its effect is mediated by beta-adrenergic
      receptors.

PMID- 8294141
TI  - Production of interferon-gamma and interleukin-4 by human T cells recognizing
      Leishmania lipophosphoglycan-associated protein.
AB  - The Leishmania protein LPGAP which is co-isolated with lipophosphoglycan is a
      specific activator of T cells from individuals who have recovered from American
      leishmaniasis. We have tested the effect of LPGAP on peripheral blood mononuclear
      cells (PBMC) from Kenyan donors cured from L. donovani infections. LPGAP induced
      vigorous proliferation and production of interferon-gamma (IFN-gamma) by the
      cells. In addition PBMC incubated with LPGAP released interleukin-4 (IL-4) after
      pulsing with ionomycin and phorbol myristate acetate. Single cells were isolated
      from LPGAP-stimulated cell lines and expanded as T-cell clones. LPGAP-reactive T
      cell clones were activated by crude preparations of both promastigotes and axenic
      grown amastigote-like parasites. Among 9 CD4+ T-cell clones recognizing LPGAP,
      cells secreting predominantly IFN-gamma as well as cells secreting predominantly
      IL-4 were identified. The results show that both IFN-gamma producing (Th1-like)
      and IL-4 producing (Th2-like) T cells recognizing LPGAP are expanded after
      infection with L. donovani in humans.

PMID- 8294142
TI  - Maturational arrest from CD4+8+ to CD4+8- thymocytes is caused by the bone marrow
      derived cells in LEC mutant rats.
AB  - LEC rats exhibit a congenital maturational arrest from CD4+8+ to CD4+8- but not
      to CD4-8+ cells in the thymus. To elucidate a cause of this mutation, bone marrow
      (BM) chimera rats were made between LEC and normal (WKAH) rats. In (WKAH-->LEC)
      BM chimera rats, donor-derived T cells matured normally, suggesting that LEC rat
      thymic stroma has a normal ability in supporting thymocyte differentiation. On
      the other hand in (LEC-->WKAH) BM chimera rats, LEC rat BM-derived T cells showed
      the arrest of maturation from CD4+8+ to CD4+8- cells in spite of having normal
      functions of WKAH rat-derived thymic stroma. In these chimeric rats, even though
      the maturational arrest from CD4+8+ to CD4+8- cells occurred in the thymus, CD4+
      cells were found in peripheral lymph nodes (LNs), suggesting that these CD4+
      cells differentiated extrathymically. These results suggest that the maturational
      arrest from CD4+8+ to CD+8- thymocytes is caused by BM-derived cells but not by
      thymic stroma.

PMID- 8294143
TI  - Expression of biologically active C3a as fusion proteins.
AB  - We selected three kinds of plasmids for expression of C3a as fusion proteins. The
      proteins were purified by affinity chromatography using the respective specific
      resins, and their activities were measured by guinea pig platelet aggregation. We
      showed that polyhistidine (polyHis)-C3a fusion protein was able to exhibit 30% of
      the activity of natural C3a. However, glutathione S-transferase (GST)-C3a fusion
      protein exhibited only 10% of such activity, and no activity was measured for
      maltose binding protein (MBP)-C3a fusion protein. The purified polyHis-C3a fusion
      protein was attached to the Ni-NTA agarose column in an attempt to isolate the
      C3a receptor from guinea pig platelets. The C3a binding protein isolated from
      digitonin-solubilized guinea pig platelet membrane was approximately 50 kDa on
      SDS-polyacrylamide gel. This is the first report of C3a fusion protein production
      with biological activity.

PMID- 8294144
TI  - An antiserum reacts with an evolutionary conserved region in the epsilon subunit
      of the T-cell receptor-CD3 complex in phylogenetically distant species.

PMID- 8294145
TI  - Effect of anti-alkaline phosphatase monoclonal antibody on B lymphocyte function.
AB  - Alkaline phosphatase (APase) is a glycosylphosphatidyl-inositol (GPI)-anchored
      protein appearing on the membranes of mitogen-stimulated B cells after
      progression into S phase of the cell cycle. Maximal APase expression occurs after
      peak proliferation and precedes maximal immunoglobulin (Ig) secretion. While
      APase is clearly an activation marker for mitogen-stimulated B cells, the
      physiologic role of APase in B cells has not been defined. Other GPI-anchored
      proteins have been assigned roles in transmembrane signaling since treatment with
      specific monoclonal antibodies (mAbs) can modulate and/or mimic the effect of
      mitogens or antigens. Thus, as an initial attempt to determine whether membrane
      APase (mAPase) plays a role in B cell activation, rat splenic B cells were
      treated with anti-APase specific mAb in the presence and absence of LPS plus
      dextran sulfate, known B cell mitogens. Anti-APase mAb alone did not induce
      proliferation or modulate mitogen-induced proliferation as measured by
      [3H]thymidine uptake and viable cell recoveries. However, the mAb augmented IgM
      secretion when used in a soluble form or cross-linked with anti-Ig. Both soluble
      and immobilized anti-APase mAb decreased the expression of APase activity by
      mitogen-stimulated B cells. Based upon these results we propose: (1) that
      transmembrane signaling may occur through mAPase as described for other GPI
      anchored proteins such as Thy-1, CD55, CD59, CD24, CD73, Fc gamma III, Qa-2, Ly
      6A/E and LFA-3, and (2) this signaling may be regulated by changes in protein
      phosphorylation caused by modulation of cellular phosphatases, specifically
      APase.

PMID- 8294146
TI  - Divergence between delayed-type hypersensitivity (DTH) to polyoma tumor
      associated antigen and antitumor efficacy in polyoma-bearing recipients of
      therapeutic non-cytolytic, DTH-mediating lymphocytes.
AB  - Soluble polyoma tumor-associated antigen (TAA) restimulation of splenocytes from
      polyoma-bearing mice led to production of non-cytolytic lymphocytes of helper
      cell phenotype which after i.p. administration mediate inhibition of polyoma and
      delayed-type hypersensitivity (DTH) to polyoma TAA. The maximum efficacy of the
      two activities was found in cells isolated on day 9 when also the highest
      percentage of L3T4+ cells was measured. The different rates of decline along with
      the extended life of the culture, and also the different degrees of dependence on
      the recipient's immune system, indicate that these processes are independent. The
      range of tail swelling in tumor-bearing recipients of immunotherapy reflects only
      the DTH transfer activity and not the range of cooperation between the
      recipient's immune system and the transferred T-helper lymphocytes leading to in
      vivo generation of CTL.

PMID- 8294147
TI  - Astrocytes and neurons regulate the expression of the neural recognition molecule
      janusin by cultured oligodendrocytes.
AB  - Janusin (formerly designated J1-160/180) is an extracellular matrix glycoprotein
      highly homologous to tenascin, consisting of two major molecular forms of 160 and
      180 kD expressed by oligodendrocytes and in myelin. Janusin expression is
      upregulated during myelination and in the adult it remains expressed at lower
      levels. It is also present at the node of Ranvier, where myelin, axon, and
      astrocytic process are in close contact. To gain an understanding of the
      regulatory mechanisms which may underlie expression of janusin, the
      differentiation stage-dependent expression of janusin was studied in cultures
      enriched in mouse oligodendrocytes and their precursor cells. Expression of
      janusin by these cells was highest on both A2B5+ and O4+/O1- oligodendroglial
      precursor cells and a subset of myelin associated glycoprotein-positive (MAG+)
      oligodendrocytes. Hardly any of the more differentiated O1+ or O10+
      oligodendrocytes expressed janusin. Expression of janusin was influenced by co
      culture with astrocytes or neurons. Astrocytes or astrocytic-conditioned culture
      supernatants elevated the expression of janusin by the more differentiated
      oligodendrocytes (O1+ or MAG+ cells), while its expression by oligodendroglial
      precursor cells was relatively unchanged. Platelet-derived growth factor, but not
      basic fibroblast growth factor, also elevated the expression of janusin by O1+ or
      O10+ oligodendrocytes. In contrast, co-culture with neurons originating from
      dorsal root ganglia or spinal cord decreased the expression of cell-bound janusin
      by oligodendrocytes and their precursor cells. These observations indicate that
      expression of janusin on these cells in culture is susceptible to opposing
      regulatory influences from astrocytes and neurons. Such influences may modulate
      the temporal and spatial distribution of janusin in the developing and adult
      central nervous system.

PMID- 8294148
TI  - Rat ciliary neurotrophic factor (CNTF): gene structure and regulation of mRNA
      levels in glial cell cultures.
AB  - The structure of the rat ciliary neurotrophic factor (CNTF) gene and the
      regulation of CNTF mRNA levels in cultured glial cells were investigated. The rat
      mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the
      region upstream of the transcription start-site did not reveal a typical TATA-box
      consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann
      cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old
      astrocyte-enriched cell cultures from new-born rat brain contained easily
      detectable CNTF mRNA. In astrocyte-enriched cultures, upregulation of CNTF mRNA
      levels was observed after treatment with IFN-gamma. CNTF mRNA levels were down
      regulated in these cells by treatments that elevate intracellular cyclic AMP and
      by members of the fibroblast growth factor (FGF) family. The implications of
      these results for potential in vivo functions of CNTF are discussed.

PMID- 8294149
TI  - Transient presence of GABA in astrocytes of the developing optic nerve.
AB  - Immunostaining and high-pressure liquid chromatography (HPLC) were used to study
      the developmental time course of astrocytic gamma-aminobutyric acid (GABA)
      expression in rat optic nerve. GABA immunostaining was carried out on cultured
      astrocytes, and on whole optic nerve. Confocal scanning laser microscopy was used
      to obtain optical sections in excised whole tissue in order to localize the
      cellular origins of GABA within the relatively intact optic nerve. GABA
      immunoreactivity was localized in astrocytes identified by GFAP staining; GABA
      staining was most intense in early neonatal optic nerve and attenuated over 3
      weeks of postnatal development. The staining was pronounced in the astrocyte cell
      bodies and processes but not in the nucleus. There was a paucity of GABA
      immunoreactivity by postnatal day 20, both in culture and in whole optic nerve. A
      biochemical assay for optic nerve GABA using HPLC indicated a relatively high
      concentration of GABA in the neonate, which rapidly attenuated over the first 3
      postnatal weeks. Immunoreactivity for the GABA synthesis enzyme glutamic acid
      decarboxylase (GAD) was pronounced in neonates but also attenuated with
      development. These results indicate that GABA and the GABA synthesis enzyme GAD
      are localized in astrocytes of optic nerve, and that their expression is
      transient during postnatal development.

PMID- 8294150
TI  - Characterization of the peripheral-type benzodiazepine receptors in cultured
      astrocytes: evidence for multiplicity.
AB  - In mammalian brain peripheral benzodiazepine (PBZD) receptors are predominantly
      localized on astroglial cells. Previous studies utilizing whole membrane
      preparations from brain and peripheral organs of various species have indicated
      several distinctions between the drug-receptor interactions of the two prototypic
      PBZD receptor ligands, PK 11195 and Ro5-4864. The present study was undertaken to
      determine whether putative differences in the binding of PBZD receptor ligands in
      homogenates of primary astrocyte cultures can be interpreted as the labeling of
      PBZD receptor subtypes. Equilibrium competition and saturation binding
      experiments in homogenate preparations of primary astrocytes from cerebral cortex
      of new born rats revealed that [3H]PK 11195 labels twice the number of [3H]Ro5
      4864 binding sites. Unlabeled Ro5-4864 competes for [3H]PK 11195 binding in a
      manner suggesting the existence of multiple PK 11195 binding sites. The
      competition binding experiments, using various benzodiazepines, indicate that one
      binding component of PK 11195 corresponds to Ro5-4864 binding sites, whereas the
      second is different. The latter binding site does not correspond to the central
      BZD receptor but displays the pharmacological properties of the PBZD receptor.
      Further differences between the binding of PK 11195 and Ro5-4864 in astrocytes
      were detected in the presence of ethanol which was more effective in inhibiting
      the binding of the latter. Subcellular distribution studies indicated, however,
      that the binding of both [3H]PK 11195 and [3H]Ro5-4864 is associated primarily
      with the mitochondrial fraction of astrocytes. Taken together, the present study
      indicates the existence of non-overlapping PBZD binding sites in astrocytes and
      thus suggests the existence of PBZD receptor subtypes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8294151
TI  - The neurotrophic analogue of ACTH(4-9) reduces the perineuronal microglial
      reaction after rat facial nerve crush.
AB  - Following peripheral nerve crush, microglial cells proliferate and migrate to
      motoneuron cell bodies of the injured nerves. Newly formed glial processes
      displace nerve terminals from the cell bodies. This process is known as synaptic
      stripping. In animal models of peripheral nerve diseases, the ACTH(4-9) analogue,
      ORG2766, was shown to facilitate axonal regeneration and to protect against
      experimental neuropathy. In the present study we examined the effect of ORG2766
      on the microglial reaction. After facial nerve crush, rats were treated with
      either ORG2766 (75 micrograms/kg/48 h) or saline and were killed on day 2-6 after
      operation. Blind counting of the number of perineuronal glial cells in the facial
      nucleus was used to assess the effect of ORG2766 treatment on the microglial
      reaction. In the saline-treated animals the number of perineuronal glial cells
      per motoneuron cell body on the crushed side increased significantly. This number
      increased up to day 5 after operation and decreased significantly from day 5 to
      6. After an initial increase in the peptide-treated animals, however, the number
      of perineuronal glial cells remained constant from day 3 onwards. Hence, on post
      operation days 4 and 5, this number was significantly less than that seen in
      saline-treated animals. Microglial cells proliferate, presumably through
      signalling by injured motoneurons. It is suggested that the decrease in the
      number of perineuronal glial cells in the ORG2766-treated animals is the result
      of a peptide-induced reduction in the release of mediating signals/cytokines or,
      alternatively, increased protection of motoneurons by stress proteins. Further
      research should address the mechanism of action of ORG2766 in animal models of
      motoneuron disease.

PMID- 8294152
TI  - Astrocytes in the nonmyelinated lamina cribrosa of the rat are less polarized
      than in the optic nerve proper: a freeze-fracture study.
AB  - Astrocytes in the lamina cribrosa of the adult rat optic nerve which is devoid of
      myelination were investigated by means of quantitative freeze-fracturing. The
      orthogonal arrays of particles (OAPs) were found to be less concentrated in the
      membranes of subpial endfeet when compared to the OAP concentration in endfeet of
      the optic nerve proper. This result corresponds to that found previously in the
      myelin deficient rat (Rohlmann et al: Glia 5:259, 1992) suggesting that lack of
      myelination generally correlates with altered astrocytes.

PMID- 8294153
TI  - Diamond: the biomaterial of the 21st century?

PMID- 8294154
TI  - Dialysis delivery versus dialysis prescription.

PMID- 8294155
TI  - Artificial pancreas, glucose sensors and the impact upon diabetology.

PMID- 8294156
TI  - Hemodialysis: evidence of enhanced molecular clearance and ultrafiltration volume
      by using pulsatile flow.
AB  - We describe several in vitro experiments showing evidence that pulsatile flow
      hemodialysis enhances ultrafiltration volume and molecular clearance as compared
      with steady flow hemodialysis. A new pulsatile pump and a conventional roller
      pump were compared using different hollow fiber dialyzers and a simulated blood
      solution containing urea, aspartame and vitamin B-12 at different flow rates and
      configurations. Ultrafiltration volume and concentration of urea, aspartame and B
      12 were measured and molecular clearance (K) calculated. Ultrafiltration volume
      markedly increased with pulsatile flow. After 10 min K for urea with pulsatile
      flow was higher in all experiments even when ultrafiltration was prevented.
      Clearance of aspartame and B-12 also increased with pulsatile flow. We propose
      three mechanisms by which pulsatile flow is more efficient than steady flow
      hemodialysis: greater fluid energy, avoidance of molecular channeling and
      avoidance of membrane layering. We hypothesize that using pulsatile flow in
      hemodialysis can significantly shorten the duration of dialysis sessions for most
      of the patients, and consequently reduce the duration of the procedure and its
      cost.

PMID- 8294157
TI  - Alterations in erythrocyte morphology induced by blood pumps.
AB  - A scanning electron microscopy was used after in vitro and in vivo tests to
      investigate any alterations caused by the peristaltic roller pump in erythrocyte
      morphology. The electron micrographs of samples were examined as follows: 1) by
      image analyser; 2) by applying Bessis's classification for the qualitative study
      of crenated red blood cells (RBCs). The in vitro test was repeated four times
      using blood from healthy donors. Each basal blood sample was divided into 250 ml
      portions, each of which was recirculated for 12 minutes at different flow rates.
      In order to verify any persistent erythrocyte damage caused by the peristaltic
      pump, 15 minutes after recirculation at 450 ml/min, another sample was prepared
      using the blood remaining from the last test. A statistically significant direct
      correlation was found between blood flow (Qb) increase and the percentage of
      morphologically altered RBCs, when either using an image analyser (r = 0.97; p <
      0.05) or Bessis's classification (r = 0.95; p < 0.05). However, neither method
      showed any statistically significant difference between the percentage of
      deformed RBCs, determined in the basal sample, or in the percentage found at the
      end of the 450 ml/min test after standing 15 minutes at room temperature. The in
      vivo test was carried out on 6 patients over 2 dialysis sessions, which differed
      only for the Qb: 250 versus 400 ml/min. The two dialysis sessions gave comparable
      results when using both study methods regarding the presence of deformed
      RBCs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294158
TI  - Myoglobin elimination in end stage kidney disease patients on renal replacement
      treatment.
AB  - Increased serum myoglobin levels were previously found in patients with chronic
      renal failure. In this report we have studied the effects of dialysis on
      myoglobin elimination in patients on CAPD, IPD, cuprophan and polyacrylonitrile
      (PAN) membrane hemodialysis. Peritoneal dialysis removed a significant amount of
      myoglobin, CAPD 480 +/- 65 micrograms/day, IPD 270 +/- 25 micrograms/12 h
      treatment, while with cuprophan dialysis none, and with PAN dialysis only an
      insignificant amount of myoglobin. The serum myoglobin levels were 250 +/- 18 and
      264 +/- 14 micrograms/l on cuprophan and a 3 month dialysis on PAN membrane,
      respectively. Markedly increased serum levels were also found in CAPD and IPD
      patients on peritoneal dialysis, 227 +/- 25 and 286 +/- 32 micrograms/l
      respectively. This study has shown that there is an increased serum myoglobin
      concentration in end-stage kidney disease patients on dialysis. Although
      peritoneal membrane is permeable to myoglobin, a relatively small amount is
      removed, and the serum level in CAPD and IPD patients was not significantly
      different from the serum myoglobin concentration in hemodialysis patients.
      Furthermore myoglobin could not be removed by hemodialysis membrane and an
      analysis of its important extrarenal catabolism level points were analyzed.

PMID- 8294159
TI  - Vasoactive agents and blood pressure regulation in sequential ultrafiltration and
      hemodialysis.
AB  - Hypotension is a common and sometimes dangerous side effect of hemodialysis. Its
      etiology is multifactorial and largely unknown. Earlier studies on the role of
      endogenous blood pressure regulating agents such as catecholamines and renin have
      rendered conflicting results. We studied the influence of ultrafiltration and
      isovolemic hemodialysis separately on the plasma concentrations of the following
      blood pressure regulating agents: adrenaline, noradrenaline, dopamine,
      neuropeptide Y, calcitonin gene-related peptide (CGRP), renin (PRA), angiotensin
      II, vasopressin, aldosterone and cortisol. During isolated ultrafiltration,
      plasma levels of two strong vasoconstrictors (noradrenaline and angiotensin II)
      and one strong vasodilator (calcitonin gene-related peptide, CGRP) increased
      significantly (noradrenaline 3.24 +/- 0.60 nM to 4.31 +/- 0.55 nM; p = 0.032,
      angiotensin II 19.74 +/- 3.46 pmol/l to 28.49 +/- 7.24 pmol/l; p = 0.047) No
      symptomatic hypotension occurred. At the end of isovolemic hemodialysis, plasma
      levels of all the vasoconstricting agents had decreased to pretreatment values,
      but those of CGRP had continued to rise (from 85.3 +/- 17.6 pmol/l to 114.5 +/-
      25.3 pmol/l, p = 0.031). During isovolemic hemodialysis, blood pressure fell to
      symptomatic levels, but was restored at the end of treatment. The study shows
      that hemodialysis patients respond to fluid removal by ultrafiltration with an
      increase in plasma levels of CGRP, noradrenaline and angiotensin II. The net
      effect is an appropriate vasoconstriction and adequate blood pressure is
      maintained during isolated ultrafiltration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294160
TI  - Extracorporeal circulation in European Economic Community (ECC in EEC): 1979
      1989.
AB  - This study determines the evolution of ECC in EEC. After recollecting the great
      stages of ECC since its routinely use in open heart surgery, the study situates
      its position in the entire world taking into account several indexes like the
      Gross National Product (GNP) and its evolution, the life expectancy and some
      other factors either technical or economical. Only a coarse analysis could be
      done for Europe due to an unsteady evolution. A more detailed analysis has been
      achieved for France thanks to a greater number of data. In such a study the major
      difficulty is to estimate the relevance and consistency of data which can change
      very quickly and are provided either by companies or by other organization.

PMID- 8294161
TI  - Nonenzymatic versus enzymatic hepatocyte isolation from pig livers for larger
      scale investigations of liver cell perfusion systems.
AB  - A comparison of nonenzymatic and enzymatic hepatocyte isolation was performed on
      pig livers. The collagenase perfusion showed superior results: mean viability 72
      +/- 10% versus a maximum viability of 21% using EDTA-perfusion. A five-step
      collagenase perfusion technique, developed for pig livers enables larger scale
      investigations, in order to develop methods for hepatocyte cultures in
      therapeutical liver cell perfusion systems.

PMID- 8294162
TI  - Polyurethan-coated lumen surface of Shaldon catheters is not damaged by heparin.

PMID- 8294163
TI  - Cardiovascular effects of cocaine abuse.
AB  - Cocaine abuse is widespread in North America. It is estimated that almost one in
      every four Americans has used cocaine at least once in his/her lifetime. In the
      past two decades, cocaine related cardiovascular complications have mushroomed
      because cocaine has become cheaper and more readily available. The fundamental
      effects of cocaine on cardiovascular system are similar to those observed
      following an intense, sympathetic stimulation. Cocaine intake results in marked
      increase in blood pressure, myocardial oxygen demand and heart rate. Coronary
      blood flow, which increases in response to exercise (endogenous sympathetic
      stimulation) however, is decreased by cocaine intake. Increased demand of oxygen
      by the myocardium in the face of decreased supply in subjects with cocaine use,
      leads to myocardial ischemia, which in turn forms a substrate for most of the
      cardiovascular complications, namely, myocardial infarction, cardiac arrhythmias
      and acute pulmonary edema. Hypertension related complications, dissection and
      rupture of aortic aneurysm, hemorrhagic stroke, in addition to infective
      endocarditis, myocarditis, cardiomyopathy all occur more frequently in cocaine
      addicts. In this review, pertinent clinical pharmacology and cardiovascular risks
      associated with cocaine abuse are presented.

PMID- 8294164
TI  - Can the serum protein binding of valproic acid limit the hepatic elimination?
AB  - In the previous study, we determined the in vivo binding parameters of valproic
      acid to serum proteins in seven healthy young adults at steady-state. In this
      study, we determined the effects of serum protein binding on hepatic elimination
      with the use of observed data obtained from our previous study of valproic acid.
      A regression analysis between the binding parameters and the pharmacokinetic
      parameters was performed. In addition, the relationship between each
      pharmacokinetic parameter was also analyzed. The order of association constant
      (K) for valproic acid-serum protein was 10(-2) l/mumol. No significant
      correlation was found between the binding parameters and the rate of elimination.
      On the other hand, the average unbound serum concentration was found to be a
      significantly negative correlation with the unbound (intrinsic) clearance (p =
      0.0082). The product of association constant and concentration of free protein
      (P) correlated positively with the unbound clearance (p = 0.0233) and negatively
      with the average unbound and total serum concentrations (p = 0.0021 and p =
      0.0029, respectively). The results indicate that the membrane permeability of
      valproic acid is high and that the increase of unbound clearance accompanies
      directly the decrease of the average unbound and total serum concentrations.
      Consequently, the KP values are proportional to the unbound clearance due to the
      rapid changes of the concentration of free protein. Therefore, the dissociation
      of the valproic acid-serum protein complex is not a rate-limiting factor for
      hepatic elimination and hence the serum protein binding cannot limit the ability
      of the liver to extract drug from blood.

PMID- 8294165
TI  - Pharmacokinetics of linsidomine (SIN 1) after single and multiple intravenous
      short infusions in patients with renal insufficiency.
AB  - Pharmacokinetic measurements were performed in two groups of patients with
      coronary heart disease (CHD) after single and multiple dosing of 2 mg linsidomine
      (SIN 1). The drug was administered by intravenous short time infusion in 12 CHD
      patients with renal insufficiency (RI group, Clcr: 11 +/- 6 ml/min) and in 12 CHD
      patients with normal kidney function (control group, Clcr: 88 +/- 22 ml/min). The
      measurement of plasma concentration time courses of total SIN 1C (SIN 1 + SIN 1C)
      was found to be suitable for an estimation of the SIN 1C related half-life of the
      terminal phase (t50% = 1.5 +/- 0.5 h), as SIN 1 was eliminated from plasma
      rapidly (t50% = 12 to 20 min). Furthermore, the mean total SIN 1C plasma profiles
      were equal after single and multiple administration of the drug giving evidence
      that SIN 1C is not accumulating during repetitive dosing of SIN 1 in patients
      with renal disease. The mean maximum renal fraction of total SIN 1C excretion of
      RI-subjects (fe = 0.8 +/- 0.8% of dose) was significantly different from the
      corresponding mean value of the control group (fe(N) = 5.8 +/- 5.1% of dose). No
      differences were found for fe and fe(N) between day 1 and day 4. As SIN 1 is
      degraded in plasma very rapidly and as SIN 1C is cleared mainly extrarenally, any
      restrictions concerning repetitive SIN 1 dosage regimen should not be considered
      for CHD-patients with renal failure.

PMID- 8294166
TI  - The application of new bioavailability parameters in the bioequivalence testing
      of antimicrobial agents.
AB  - Two new bioavailability parameters were recently suggested [Koeleman et al. 1991]
      to define (i) the time that the concentration in the blood stays above a defined
      minimum effective concentration, te and (ii) the onset of the effect, to. In
      addition to conventional bioequivalence parameters, the new bioavailabilty
      parameters (to and te) were calculated in this study and statistically compared
      for penicillin, chloroquine, oxytetracycline, amoxycillin and flucloxacillin from
      available bioequivalence data. For oxytetracycline, flucloxacillin and
      amoxycillin, the conventional bioavailability parameters indicated partial
      equivalence whereas using the te and to parameters, more realistic indications of
      the possible extent of the performance of a drug from dosage forms were obtained
      than with the conventional bioequivalence parameters. The new parameters gave
      additional information for a better evaluation of the performance of a drug from
      a dosage form.

PMID- 8294167
TI  - Evaluation of the effect of different kinds of foods on the bioavailability of a
      sustained-release theophylline tablet.
AB  - Food-induced changes on the bioavailability of a sustained-release theophylline
      tablet, which uses acrylic resins Eudragit as sustaining agent, were studied in
      12 healthy male volunteers. The tablet was developed in our laboratory using
      conventional technology. It presented a good bioavailability pattern and
      maintained plasmatic concentrations within the therapeutic range for 12 hours
      under conditions of steady-state. The study design was a 4 x 4 latin square
      involving 12 subjects who received a single dose of the tablet while fasting or
      with a standardized normal, high fat or high fat/high protein meal. The results
      showed no differences in AUC, K, tmax, ka and MRT. Statistical differences were
      found in Cmax comparing the fasting condition with high fat/high protein diet. A
      delay was also observed in the detection of the drug in plasma when the tablet
      was administered with high fat and high fat/high protein food, but clinically the
      changes seem to be irrelevant.

PMID- 8294168
TI  - Influenza vaccination on renal transplant patients is safe and serologically
      effective.
AB  - Since immunosuppressed patients are at higher risk of serious influenza virus
      infection than healthy subjects, we decided to study the serological
      effectiveness of influenza vaccination on renal transplant patients, despite the
      theoretical aspect that such treatment could induce glomerular lesions through an
      immunological process. Forty transplant patients aged from 20 to 50 years with
      well functioning renal graft and no febrile episode were studied. Blood samples
      were collected before the intramuscular injection of 0.5 ml of multivalent
      influenza vaccine (PASTEUR MERIEUX SERUM VACCINS), at one and at two months after
      the vaccination. Before vaccination, the antibody titers to influenza virus
      ranged from 0 to 1/20 and after vaccination from 1/20 to 1/320. One month after
      vaccination 17/40 (42.5%), 18/31 (58%) and 16/33 (48%) patients showed a four
      fold or greater increase of serum influenza antibody titers to antigens A/H3N2,
      A/H1N1 and B, respectively. A similar response at two months in relation to the
      first month response rate after vaccination was found in 15/17 (88%), 18/18
      (100%), and 15/16 (93%) of transplant patients for the above mentioned three
      antigens. Side-effects were observed in two of the studied patients. Serum
      creatinine and urine protein were not changed. Also acute graft rejection
      episodes were not observed. It is suggested that influenza vaccination is safe
      and serologically effective on renal transplant patients.

PMID- 8294169
TI  - Netilmicin kinetics in urology.
AB  - Plasma kinetics of netilmicin, an aminoglycoside antibiotic was studied in 62
      patients undergoing urologic surgery. Despite the use of a standard 100 mg-dose,
      no toxic levels were achieved except in one patient. A poor correlation was found
      between netilmicin plasma elimination constant and creatinine clearance (r =
      0.34, p = NS). We can conclude that the prediction of netilmicin plasma
      concentrations is not possible using only demographic patient's data. The
      monitoring of netilmicin levels should be performed in long-term treatments but
      not in 4-dose regimes such as in urologic prophylaxis.

PMID- 8294170
TI  - Ketoprofen 2.5% gel versus placebo gel in the treatment of acute soft tissue
      injuries.
AB  - A parallel, double-blind, placebo controlled and randomized study in a single
      center was done with ketoprofen 2.5% gel to treat acute soft tissue injuries.
      Patients applied the gel twice a day for seven days, corresponding to 250 mg of
      ketoprofen per day. Assessments were made on the third and seventh day by VAS,
      subjective evaluation and pain threshold algometry. The study group consisted of
      29 patients and the control group 27 patients. Pain at rest was significantly
      relieved in the ketoprofen group, whereas in the placebo group the difference was
      not significant. In terms of side-effects, no difference between the groups was
      noticed. In both groups, local dermal irritation was found. Our results suggested
      that ketoprofen 2.5% gel was safe and superior to placebo in the treatment of
      soft tissue injuries.

PMID- 8294171
TI  - Double-blind comparison of butorphanol and nalbuphine on the common bile duct by
      ultrasonography in man.
AB  - Butorphanol and nalbuphine, narcotic agonist-antagonists were shown to cause no
      increase in biliary pressure in contrast to morphine in dogs or men. A non
      invasive, ultrasonographic technique confirmed that morphine caused constriction
      of the common bile duct while placebo caused no effect. To prove the lack of
      constrictive effect of butorphanol and nalbuphine on the common bile duct, the
      changes in its diameter were measured following placebo or the two agonist
      antagonists by ultrasonography. In a double-blind, randomized study, 17 patients
      undergoing open cholecystectomy were evaluated. No morphine or opioids were
      allowed for 12 hours prior to the study. After premedication with midazolam and
      glycopyrrolate, anesthesia was induced by midazolam, 50 micrograms.kg-1 and
      thiopental, 3.0-5.0 mg.kg-1. Tracheal intubation was facilitated by
      succinylcholine 1.0 mg.kg-1 and muscle relaxation was maintained with vecuronium.
      Anesthesia was maintained with isoflurane or enflurane and nitrous oxide in
      oxygen. After imaging the common bile duct by ultrasonography, placebo,
      nalbuphine 0.3 mg.kg-1 or butorphanol 40 micrograms.kg-1 were injected
      intravenously. The diameter of the common bile duct was measured before and at 4
      and 8 minutes after drug administration. One-way analysis of variance and paired
      t-test were utilized for statistical analysis. P < 0.05 was considered
      significant. No significant changes in the common bile duct diameter was observed
      after placebo administration, nor was any change observed after either nalbuphine
      or butorphanol as compared to the baseline. The comparison of three groups of
      patients showed no statistically significant difference.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8294172
TI  - Treatment programming for alcohol and drug-dependent pregnant women.
AB  - National concern regarding the problem of alcohol and drug use during pregnancy
      has brought to the forefront the lack of treatment programs specifically targeted
      to pregnant women. Many programs are seeking guidance in establishing services
      for pregnant women. Research suggests that programs that provide comprehensive,
      coordinated, and "holistic" treatment are better able to draw pregnant women into
      care as well as provide more effective treatment. This paper presents an overview
      of written guidelines and protocols for treating pregnant chemically dependent
      women, including an elaboration of guiding principles for care. Unresolved policy
      issues are identified as well as recommendations for future research directions.

PMID- 8294173
TI  - Maternal drug abuse: laws and ethics as agents of just balances and therapeutic
      interventions.
AB  - Among the many pressing legal, psychosocial, and ethical issues surrounding
      perinatal chemical dependence is one of achieving balances between far-reaching
      rights claimed for the unborn and for children, and those claimed by their
      mothers. In an attempt to achieve balances that are just and promote positive
      consequences, policies and laws have evolved that have pitted disparate
      individuals and groups against each other, most obviously mothers against their
      fetuses and children. Some such policies have had negative consequences such as
      the further weakening of already at-risk families and the erosion of
      doctor/patient trust. This article asserts that ethical concepts and legal tenets
      must be combined to develop new paradigms designed to minimize conflict and to
      achieve just and therapeutic balances between the rights and needs of those
      involved.

PMID- 8294174
TI  - Who: promising progress on HIV vaccine.

PMID- 8294175
TI  - Nurses and others settle with AIDS drug maker.

PMID- 8294176
TI  - 13 million HIV positive women by 2000.

PMID- 8294177
TI  - Quality through health policy: the Canadian example.
AB  - In Canada, as elsewhere, healthcare policymakers are being asked to make some
      tough tradeoffs between quality and cost. It is crucial that national nurses'
      associations take part in these discussions to ensure that nurses' and consumers'
      interests are well protected. The Canadian Nurses' Association has helped mould
      national health policy. In the process it has had all the advantages of influence
      and all the risks of being co-opted by the system itself. Below, an insight into
      the knowledge gained.

PMID- 8294178
TI  - Developing national health policy in Taiwan.
AB  - Since 1987 ICN has been actively encouraging national nurses' associations (NNAs)
      and their members to play a more active role in health policymaking at the local,
      national and international levels. Below the author offers her first-hand
      experience in developing national health policy since 1988, when she became
      deputy director and then director of the Bureau of Health Promotion and
      Protection at Taiwan's Department of Health.

PMID- 8294179
TI  - An association's campaign to influence policy.
AB  - When an opportunity was opened to make its voice heard in the arenas of political
      action and policy development, the New York State Nurses Association (NYSNA), a
      member of the American Nurses Association, began to implement strategies to
      achieve its policy goals. Below, the strategies it used to influence the
      policymakers on issues important to professional nursing.

PMID- 8294180
TI  - Transformational leadership: the catalyst for successful change.
AB  - Health care in the 21st century will require new visions and empowered
      professional models of nursing practice. The catalyst for this transformation
      will be a new type of leadership, as described below.

PMID- 8294181
TI  - A lesson in theory building: Japanese study of long-distance marriages.
AB  - Below are the results of a study on women's experiences in long-distance
      marriages which are relevant to nursing because they can 1) help nurses'
      understanding of human responses to actual or potential health problems; and 2)
      contribute to theory building in nursing.

PMID- 8294182
TI  - Human immunodeficiency virus type 1 tat gene enhances human papillomavirus early
      gene expression.
AB  - To investigate the possible direct/indirect role of Human immunodeficiency virus
      (HIV) as a cofactor in human papillomavirus (HPV) oncogenesis, cotransfection
      experiments were carried out in which a recombinant plasmid containing the HPV16
      long control region (LCR) linked to the chloramphenicol acetyltransferase (CAT)
      gene was cotransfected into cultured cells with a plasmid expressing HIV-1 Tat
      protein. Tat expression efficiency and transactivation activity were evaluated in
      different cell lines by cotransfecting plasmids containing the HIV tat gene and
      HIV LTR-driven CAT-coding sequences. HeLa and CaSki cell lines represented the
      most appropriate recipient cells for Tat-directed transactivation of both the HIV
      LTR and the HPV LCR promoters. Furthermore, HIV tat was transfected into HeLa
      cells (containing 10-20 copies per cell of HPV18), and HPV18 E7 protein
      expression was evaluated by a radioimmunoprecipitation assay using polyclonal
      antibodies against the E7 protein. Our results show that the Tat protein can
      transactivate the HPV LCR and increase HPV18 E7 expression in HeLa cells.

PMID- 8294183
TI  - Activation of the human immunodeficiency virus type 1 long terminal repeat by
      skin-sensitizing chemicals in transgenic mice.
AB  - Topical dinitrochlorobenzene (DNCB) is often used for evaluating contact skin
      hypersensitivity in immunocompromised patients. We have determined, in this
      study, that topical application of DNCB alone, even without induction of contact
      skin hypersensitivity, was sufficient to observe activation of the human
      immunodeficiency virus promoter (long terminal repeat) in the skin of an HIV-1
      long terminal repeat-luciferase transgenic mouse model. Such treatment might be
      contra-indicative in patients infected with the human immunodeficiency virus,
      because in earlier studies DNCB-exposed skin dendritic cells might migrate into
      draining lymph nodes which play an important role in AIDS pathogenesis.

PMID- 8294184
TI  - Subcloning and restriction enzyme mapping of bovine adenovirus type 2.
AB  - Bovine adenoviruses (BAVs), causing both respiratory and/or enteral diseases in
      cattle, have been isolated in many countries all over the world. In this study we
      report on the molecular cloning of the internal EcoRI fragments spanning 20.6
      90.5%, and the internal SalI fragments spanning 3.1-65.2% of the BAV type 2
      (BAV2; strain No. 19) genome into the plasmid vector pUC19. Moreover, the
      subcloning of the BAV2 genome facilitated the construction of a detailed physical
      restriction endonuclease map for BamHI, ClaI, EcoRI, HindIII, KpnI, NotI, NspV,
      PstI, PvuI, SalI, XbaI and XhoI.

PMID- 8294185
TI  - Two new candidate adenovirus serotypes.
AB  - Two new adenovirus (AV) subgenus D serotypes, which we propose as AV candidates
      48 and 49, are described. Both AV 48 and 49 were unique by serum neutralization
      and the pattern of restriction endonuclease fragments. By the hemagglutination
      inhibition assay there was a significant reciprocal cross between AV 48 and 44
      and one-way crosses between AV 48 and AV 37 sera and between AV 30 and AV 49
      sera. Eleven AV 48 and 5 AV 49 isolates, mainly from AIDS patients, have been
      identified at the Viral and Rickettsial Disease Laboratory.

PMID- 8294186
TI  - Serological relationships within the group E fowl adenoviruses.
AB  - Antisera were raised in chickens to six group E fowl adenoviruses (FAV) which
      have been divided into a highly virulent (hypervirulent) and a mildly virulent
      subgroup using restriction endonuclease analysis. Virus neutralisations showed
      that these two distinct restriction endonuclease groups were distinguishable
      serologically, and indicated a possible vaccine candidate for use against the
      hypervirulent FAV. The suitability of this candidate was established in challenge
      experiments where vaccination with this virus protected against challenge from
      another hypervirulent virus as well as one of the mildly virulent FAV.

PMID- 8294187
TI  - Detection of Epstein-Barr virus genome in nasopharyngeal carcinoma by in situ DNA
      hybridization.
AB  - To elucidate the possible role of Epstein-Barr virus (EBV) in nasopharyngeal
      carcinoma (NPC), we investigated the EBV genome in NPC by in situ DNA
      hybridization using radioisotope- and and biotin-labeled EBV DNA probes. The EBV
      genome was detected in the tumor cells in all (100%) 60 cases, irrespective of
      histological type, but not in the lymphocytes. Silver grains, which reflected the
      copy number of the EBV genome, were more abundant in the nonkeratinizing, spindle
      cell, and undifferentiated carcinomas than in keratinizing squamous cell
      carcinoma. In the keratinizing carcinoma, which was poorly differentiated in this
      series, the EBV genome was usually detected in anaplastic tumor cells, and not in
      the keratinizing areas. The sensitivity of the radioisotopic technique was
      superior to that of the biotinylated probe method (100 vs. 81.7%, p < 0.0003).
      These results suggest that EBV is etiologically related to nasopharyngeal
      carcinogenesis and that the differentiation of tumor cells in vivo, and probably
      also in vitro, may become incompatible with EBV replication.

PMID- 8294188
TI  - Molecular characterization of the DNA of Anatid herpesvirus 1.
AB  - A plaque-purified isolate of the Holland strain of Anatid herpesvirus (AHV-ppc3)
      was purified by differential and buoyant density sedimentation. The virus buoyant
      density was 1.215 g/cm3 in sucrose. AHV-ppc3 DNA was analyzed by sedimentation
      velocity studies in neutral or alkaline sucrose gradients. Based upon a
      comparison with T4 DNA, the DNA of AHV-ppc3 was found to have a sedimentation
      coefficient of 59.7 S and a molecular mass of 1.19 x 10(8) daltons. Between 15
      and 22 bands were observed in agarose gel electrophoresis with AHV DNA cut by
      BamHI, EcoRI, PstI or BglII. The possibility of isometric forms is indicated by
      the finding of restriction fragments having molar ratios differing from 1.0. The
      mean molecular mass calculated from the fragments was 1.18 x 10(8) daltons.
      Terminal fragments were identified using exonuclease II and BgII. In alkaline
      sucrose gradients, AHV DNA fragments with the largest of the most abundant
      species have a sedimentation coefficient of 69 S and a calculated mass of 6.0 x
      10(7) daltons. The buoyant density of AHV-ppc3 DNA in cesium chloride was 1.723
      g/cm3 corresponding to a % G + C content of 64.3. This finding was supported by
      thermal melts of the DNA in SSC/10 in which the thermal melting point was 82.7
      degrees. The data support a model for AHV in which the viral duplex DNA is
      linear, without covalently closed termini or significant base modifications, but
      with single strand nicks or gaps. The % G + C content of AHV DNA is the highest
      reported for any avian herpesvirus in the alpha-herpesvirinea subgroup.

PMID- 8294189
TI  - Prevalence of headache in a representative sample of the population in a French
      department (Haute-Vienne-Limousin).
AB  - In 1986-1987, a neuroepidemiologic survey was undertaken to study the prevalence
      of the most frequently encountered neurologic disorders, and in particular
      headache, in a representative sample of the population in the Haute-Vienne
      Department (Limousin). A door-to-door survey was made using a protocol developed
      by the W.H.O. at the beginning of the 1980's. The calculated prevalences
      (according to Poisson's distribution) per 100,000 inhabitants were 5,059 for
      nonmigraine headache, and 4,270 for migraine headache. This disorder
      preferentially affected young adults and essentially involved females. It was the
      most frequently encountered disorder (50%) during the different surveys of
      similar methodology.

PMID- 8294190
TI  - Disruption of the immunopeptidergic network in dietary migraine.
AB  - This investigation is devoted to the study of the time-course of a cytokines
      panel (IL-4, IL-6, IFN-gamma, GM-CSF) in plasma samples from migraine patients.
      The data obtained during challenged migraine crises was compared to the baseline
      values. Time-data series analysis showed a fall after a challenge test for IL-4
      and IL-6 plasma levels and an opposite trend for gamma-IFN and GM-CSF levels. The
      implication of this phenomenon in dietary migraine is not readily evident. There
      may possibly be an activation of this cytokine network together with the well
      known impairment in the neuropeptidergic system, considering the close links
      between interleukins and other cytokines and the neuro-mediators of pain, such as
      histamine and 5-HT.

PMID- 8294191
TI  - Intravenous acetylsalicylic acid inhibits central trigeminal neurons in the
      dorsal horn of the upper cervical spinal cord in the cat.
AB  - Acetylsalicylic acid (ASA) is one of the most commonly used substances in the
      treatment of headache and other pain syndromes. It is only recently that its
      efficacy in the treatment of acute attacks and in the prophylaxis of migraine has
      been proven in clinical trials. Various peripheral and central mechanisms have
      been proposed for the analgesic effects of acetylsalicylic acid and its mode of
      action in migraine. The possible actions of acetylsalicylic acid in migraine
      include local analgesic effects, changes in cerebral serotonin turnover,
      modulation of antinociceptive neurons in the hypothalamus and inhibition of the
      release of algogenic peptides during neurogenic inflammation. In this study
      trigeminal somatosensory evoked potentials and single unit activity of central
      trigeminal neurons in the dorsolateral C2 spinal cord were monitored during
      electrical stimulation of the superior sagittal sinus in the cat. Intravenous
      administration of the soluble acetylsalicylic salt (acetylsalicylic lysinate, 30
      mg/kg) reduced the peak-to-peak amplitudes of somatosensory evoked potentials
      from 219 +/- 11 mV by 18% after 45 minutes and by 26% after 60 minutes. Naloxone
      injection (0.5 mg/kg and 1.5 mg/kg) did not reverse the inhibition caused by ASA.
      The probability of trigeminal cell tiring was reduced in 63% percent of the
      monitored single units. The effect was not mediated through naloxone-sensitive
      opioid receptors and was independent from ASA-induced peripheral blockade of
      neuropeptides during neurogenic inflammation. The non-steroidal anti-inflammatory
      agent ketorolac (0.4 mg/kg, IVI) a new cyclooxygenase inhibitor, also reduced the
      somatosensory evoked potentials by 30% following the same time course.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8294192
TI  - Autonomic function testing in patients with migraine.
AB  - Autonomic nervous system function was studied in 62 patients with migraine. The
      Valsalva maneuver, deep breathing test, sustained handgrip test, orthostatic test
      and spectral analysis of heart rate variability in the supine and standing
      positions were performed in a group of 62 patients of both sexes, aged 21 to 50
      years, and in an age-matched control group of 45 healthy volunteers. Heart rate
      increases during sustained handgrip was significantly reduced in the headache
      group, when compared to the control group, while the results of the remaining
      cardiovascular tests did not significantly differ between the control and
      headache groups. In standing patients, the integrals of middle frequency bands of
      amplitude spectra were smaller in patients than in controls because the increase
      induced by standing was smaller in migraine patients. The results in patients
      with migraine with aura (21 patients) and migraine without aura (41 patients) did
      not differ significantly from each other. The same was true for the results of
      the female and male patients. It is concluded that sympathetic function is
      impaired in migraine patients.

PMID- 8294193
TI  - Chronic paroxysmal hemicrania (CPH) and hemicrania continua: transition from one
      stage to another.
AB  - Two female patients, one suffering from CPH in non-remitting form, and the other
      from hemicrania continua, in the pre-chronic (non-continuous) stage are
      described. Both were followed through transitions to other stages: the CPH
      patient was followed from the non-remitting stage to a longlasting remission, and
      lastly back to another chronic stage. Indomethacin was effective in all the
      symptomatic stages. The hemicrania continua patient was followed from the non
      continuous to the continuous stage. Indomethacin was effective in both stages.
      These observations provide further evidence that the non-chronic and chronic
      ("remitting" and "non-remitting") stages of CPH belong together. The same seems
      to apply to the two stages of hemicrania continua, the "continuous" and the "non
      continuous" stages.

PMID- 8294194
TI  - Headaches from chemical exposures.
AB  - Headaches are a common complaint after work place or environmental exposures. A
      striking index case led to a literature review which uncovered only limited
      information. We then performed a retrospective descriptive study of 50 subjects
      referred to University Clinics with the complaint of headaches associated with
      chemical exposures at their work place. Our data suggest a different headache may
      exist depending on whether the chemical exposure is routine and limited versus
      accidental and extensive. Low level work place chemical exposures appear to cause
      headaches that abate soon after cessation of the exposure. A single accidental
      and extensive exposure may lead to patient complaints of a new headache syndrome
      that may last from several months to years. The characteristics associated with
      the onset of a new headache syndrome from accidental chemical exposures includes:
      1) An acute large quantity of exposure. 2) A short latency of onset of the
      heralding headache. 3) A severe intensity and long duration of the heralding
      headache. 4) New recurring headaches that were not experienced before the acute
      exposure. We suggest a possible term for this high exposure syndrome i.e.
      Chemical Headache Exposure Syndrome (CHES).

PMID- 8294195
TI  - Current emergency treatment of severe migraine headaches.
AB  - OBJECTIVE: To compare the efficacy of the combination of meperidine and
      hydroxyzine IM, versus dihydroergotamine and metoclopramide IV in the treatment
      of severe migraine headaches. DESIGN: This was a randomized double-blind, double
      dummy study. SETTING: Established patients, whose headache had failed to respond
      to their usual abortive agent, were invited to an out-patient headache clinic for
      the study. PATIENTS: Twenty-eight patients, diagnosed as suffering from either
      migraine headache or chronic daily headache, were screened on arrival to exclude
      life-threatening causes. INTERVENTION: Group A (14 patients) received
      dihydroergotamine 1mg and metoclopramide 10mg IV and a placebo injection IM, and
      Group B (14 patients) received meperidine 75mg and hydroxyzine 75mg IM and a
      placebo injection IV. MAIN OUTCOME MEASURES: Patients rated their headaches on a
      scale of 0-3 prior to treatment and again at 30 and 60 minutes. RESULTS: Both
      groups experienced improvement in headache severity. (Group A P = 0.001 and Group
      B P = 0.003). Improvement in pain scale score was greater for Group A than Group
      B. (P = 0.006). The number of patients having a mild or no headache in Group A
      (13/14) was significantly greater than Group B (3/14). (P < 0.001) CONCLUSIONS:
      The combination of dihydroergotamine and metoclopramide IV should replace the
      standard IM narcotic and anti-emetic as the parenteral treatment of choice for
      severe migraine headache.

PMID- 8294196
TI  - Migraine and intracranial vascular malformations.
AB  - The relationships between migraine and A-V Malformations is a subject of
      controversy and the arguments are mainly based on case reports and retrospective
      data. To clarify this subject a structured inquiry and classification of
      headaches in large samples of patients with intracranial vascular malformations
      (IVM) is essential. The authors studied the prevalence of headaches in 51
      patients with IVM admitted to our Department, between 1984 and 1992. The methods
      used were a review of medical records followed by a self-administered headache
      questionnaire and clinical interview using the IHS criteria for the diagnostic
      classification of headaches. The relative frequency of the different types of
      headaches was calculated and compared with the general population data. A
      correlative study of the headache characteristics with the type and location of
      the IVM was made. A high prevalence (47%) of migraine type headaches and a strong
      positive correlation (88.8%) between the site of AVM and side of the pain was
      found. This is highly suggestive but not conclusive of a pathophysiologic
      relationship between these entities. The conclusion drawn is that a prospective
      study of headaches by questionnaire or semi-structured clinical interview in
      patients with IVM is essential to discover the effective prevalence and
      characteristics of headaches associated with IVM and their relationships.

PMID- 8294197
TI  - Musculoskeletal dysfunction of the neck in migraine and tension headache.
AB  - In this prospective controlled study, thirty-seven migraine and/or tension
      headache patients and thirty-seven age and sex matched controls were examined for
      evidence of musculoskeletal dysfunction in the neck. The examination consisted of
      clinical range of motion testing of neck rotation, sidebending, flexion and
      extension while in the sitting position. The headache group had more abnormal
      physical findings than the control group. Although the difference for each
      particular motion test, taken by itself, was not statistically significant, two
      or more abnormalities in combination was found to reach a .05 confidence level of
      significance. It is proposed therefore that musculoskeletal dysfunction of the
      neck is a contributing factor to the etiology of migraine and tension headache.

PMID- 8294198
TI  - Comparison of contingent negative variation between migraine interval and
      migraine attack before and after treatment with sumatriptan.
AB  - We compared in a placebo controlled, double blind, crossover within-subject
      design, the amplitude and area integral of contingent negative variation (CNV)
      using a 2 second interstimulus interval in migraine patients between attack and
      interval before and after treatment. The study was conducted on 14 female
      subjects suffering from migraine without aura. The measurements were performed in
      a balanced sequence at four different times on each patient, twice during the
      migraine interval and once in each of two migraine attacks. The CNV in the
      patients was measured first (baseline), then medication was administered on a
      double-blind basis with an autoinjector, using either 6 mg sumatriptan or a
      placebo solution. Thirty minutes after administration the CNV parameters were
      measured again and the changes between pre- and post-treatment were taken as
      dependent variables. CNV amplitude baseline readings did not differ significantly
      between the four conditions. Neither administration of placebo nor sumatriptan
      led to a significant change in CNV parameters independent of whether significant
      clinical improvement of migraine headache occurred or not. According to our
      findings CNV-mechanisms between attack and interval are not subject to short-term
      changes, even though a small, not significant tendency towards a decrease in CNV
      amplitude during migraine attacks appears to exist. Therefore, it can be assumed
      that changes in the systems which are depicted by CNV readings are not involved
      in initiating and terminating acute migraine attacks.

PMID- 8294199
TI  - Hb Melusine [alpha 114(GH2)Pro-->Ser]: a new neutral hemoglobin variant.
AB  - Hb Melusine [alpha 114(GH2)Pro-->Ser] was found in an Algerian patient during a
      systematic screening for hemoglobinopathies performed in Luxembourg. The abnormal
      hemoglobin was suspected when a thickening of the Hb A band was observed by
      isoelectrofocusing. The mutant hemoglobin was silent in all other electrophoretic
      methods used for presumptive diagnosis with the exception of globin
      electrophoresis in the presence of Triton X-100. This technique revealed an alpha
      chain considerably more hydrophobic than normal. The structural abnormality of Hb
      Melusine concerns position alpha 114(GH2) that belongs to a cluster of
      hydrophobic residues localized in the N-terminal half of the alpha T-12b tryptic
      peptide. It has been shown in the case of another variant of that position (Hb
      Nouakchott), that the replacement of the Pro GH2 by a Leu was responsible for a
      dramatic increase in the retention time of the alpha polypeptide chain during
      reversed phase high performance liquid chromatography, much higher than that
      reported for similar substitutions in other regions of the hemoglobin molecule.

PMID- 8294200
TI  - Hb Val de Marne [alpha 133(H16)Ser-->Arg]: a new hemoglobin variant with moderate
      increase in oxygen affinity.
AB  - Hb Val de Marne [alpha 133(H16)Ser-->Arg] was found in a French family during a
      neonatal hemoglobinopathy screening program. The abnormal hemoglobin was found,
      within a few months interval, in two newborn children who were first cousins. In
      the children as well as in the parents carrying this hemoglobin variant, the red
      cell parameters were normal. Hb Val de Marne, isolated by isoelectrofocusing,
      displayed a slightly higher auto-oxidation rate than Hb A. Its oxygen affinity
      was increased 1.7-fold in comparison to that of Hb A. The heterotropic effects
      were normal.

PMID- 8294201
TI  - Identification of Hb C [beta 6(A3)Glu-->Lys] in a Thai male.
AB  - The propositus was a 29-year-old Thai male, whose electrophoretic pattern showed
      Hb A (58%) plus an abnormal hemoglobin (42%) with mobility identical to Hb A2 and
      Hb E. Protein sequencer analysis and tryptic peptide mapping of the beta chain
      indicated that the abnormal hemoglobin was Hb C [beta 6(A3)Glu-->Lys], rather
      than Hb E which is more commonly found in South East Asia. This conclusion was
      confirmed by direct sequence analysis of the propositus' DNA, which showed AAG as
      well as GAG at codon 6 of the beta gene, in agreement with heterozygosity for Hb
      C and Hb A. Furthermore, the beta gene framework (Ava II-, Bam HI+) of the
      propositus suggested that the beta C gene may have arisen from an independent
      mutation. Since Hb C and Hb E have the same mutation (Glu-->Lys) in the beta
      chain, although at different positions, and behave similarly in electrophoresis,
      cases of Hb C and Hb E may sometimes have been mistakenly identified for each
      other, based on whichever variant is most prevalent in the particular population.

PMID- 8294202
TI  - Beta-thalassemia in southwestern Iran.
AB  - Seventeen unrelated beta-thalassemia patients or carriers from Southwestern Iran
      were examined for the beta-globin gene mutations by polymerase chain reaction
      amplification of the beta-globin gene and direct genomic sequencing, or by the
      method of allele-specific oligonucleotide hybridization. Their clinical and
      hematological characteristics were also recorded. Of 26 potential thalassemia
      causing chromosomes examined, 10 different mutations were found. The IVS-II-1 (G-
      >A) mutation was the most frequent (31%) followed by the IVS-I-6 (T-->C) mutation
      (15%). Eight mutations were initially described in Mediterranean populations and
      two were of Kurdish origin. Four of these mutations, both initially described in
      the Mediterranean region, are reported here for the first time in Iranians. The
      unexpectedly high number of different mutations that account for beta-thalassemia
      in this region of Iran suggest migration of chromosomes from distant places and
      genetic admixture.

PMID- 8294203
TI  - Allele-specific amplification for the identification of several hemoglobin
      variants.
AB  - Eight known abnormal hemoglobins in more than 40 patients have been identified
      with an allele-specific amplification procedure. These are mutants of the A gamma
      (Hb F-Sardinia), the delta (Hb B2), the alpha (Hb G-Philadelphia), and the beta
      (Hbs S, C, E, D-Los Angeles, O-Arab) globin genes. Adjustment to an unusually
      high annealing temperature improves the procedure greatly, allowing excellent
      discrimination between normal and mutant alleles, irrespective of the particular
      mismatch. The discrimination includes the Hbs C and E in the same reaction
      mixture-multiplex allele-specific amplification. The procedure can successively
      use primers with 3'-penultimate critical nucleotides, degenerative ends, and
      potentially dimerizing properties.

PMID- 8294204
TI  - Hb Porto Alegre or alpha 2 beta 29(A6)Ser->Cys in unrelated families of the
      Canary Islands.

PMID- 8294205
TI  - Hb A2-liangcheng [delta 117(G19)Asn->Asp(AAC->GAC)]: a new delta chain variant
      detected by gene analysis in a Chinese family.

PMID- 8294206
TI  - Hb Higashitochigi (Hb Ht) [ beta 24(B6) or beta 25(B7) glycine deleted]: a new
      unstable variant expressing cyanosis.

PMID- 8294207
TI  - Haplotype-specific sequence variations in the locus control region (5'
      hypersensitive sites 2, 3, 4) of beta S chromosomes.

PMID- 8294208
TI  - The beta- and delta-thalassemia repository (7th edition).

PMID- 8294209
TI  - Multidrug resistance: mechanism and therapy.

PMID- 8294210
TI  - Identification of human T cell leukemia virus type IIb infection in the Wayu, an
      aboriginal population of Colombia.
AB  - Human T cell leukemia virus type II (HTLV-II) is endemic in a number of native
      American populations and high rates of infection have also been demonstrated in
      intravenous drug abusers (IVDAs). Studies of virus isolates in the latter
      population have shown the existence of two closely related subtypes of the virus,
      HTLV-IIa and HTLV-IIb. To characterize the viruses present in native Americans,
      we analyzed by nucleotide sequence analysis the proviruses from the Wayu, an
      aboriginal population residing in Colombia, South America. The results showed
      HTLV-IIb infection in this population, and also demonstrated remarkable
      conservation of sequence when compared to the proviruses in IVDAs.

PMID- 8294211
TI  - Chromosomal assignment of the gene for protein tyrosine phosphatase HPTP delta.
AB  - Protein tyrosine phosphatase (PTP) negatively regulates the effect of protein
      tyrosine kinases and is implicated in the regulation of a variety of biological
      phenomena such as cell activation, differentiation and neoplastic transformation.
      To gain insight into the role of PTPs, we cloned the human receptor-type PTP gene
      and assigned the chromosome harboring the gene for HPTP delta by using DNAs from
      human-mouse hybrid cell lines and by fluorescence in situ hybridization. The
      results clearly demonstrated that HPTP delta gene maps to human chromosome 9p24.

PMID- 8294212
TI  - Prognostic significance of selected lifestyle factors in urinary bladder cancer.
AB  - To examine the prognostic significance of lifestyle factors in urinary bladder
      cancer, we conducted a follow-up study of 258 incident bladder cancer patients,
      who were originally recruited in a case-control study in metropolitan Nagoya.
      Information on individual survivals was obtained from the computer data-file of
      the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate
      analyses revealed significant associations of 5-year survivorship with
      educational attainment, marital status, drinking habits and consumption of green
      tea in males, and age at first consultation, histological type and grade of
      tumor, stage and distant metastasis in both sexes. After adjustment for age,
      stage, histology (histological type and grade) and distant metastasis by means of
      a proportional hazards model, drinking of alcoholic beverages was significantly
      associated with the prognosis of bladder cancer in males. Its adjusted hazard
      ratio was 0.46 (95% confidence interval: 0.26-0.79), favoring patients who had
      taken alcoholic beverages. In detailed analysis, ex-drinkers and all levels of
      current drinkers demonstrated hazard ratios smaller than unity, although no clear
      dose-response relationship was detected. No prognostic significance was found for
      such lifestyle factors as smoking habit, uses of artificial sweeteners and
      hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and
      cola.

PMID- 8294213
TI  - Progression of a weakly tumorigenic mouse fibrosarcoma at the site of early phase
      of inflammation caused by plastic plates.
AB  - To elucidate tumor progression-enhancing factor(s), we examined the effects of
      host inflammation and host immunological status on in vivo tumor progression. One
      x 10(4) cells of QR clones (QR-32, -20 and -18), regressor tumor clones of 3
      methylcholanthrene-induced fibrosarcoma, were unable to grow when injected s.c.
      into C57BL/6 mice in cell suspension form. However, QR clones grew and were
      lethal when s.c. implanted, attached to plastic plates. Furthermore, the tumor
      lines (QRpP) obtained from the tumors which had arisen from the plate-attached QR
      32 clone cells no longer required plastic plates for their growth in normal mice,
      and had acquired stable malignant phenotypes. Although QR-32 cells became lethal
      when injected at the site of plastic plate implantation 1, 5 and 10 days before
      tumor injection, few tumors developed when plastic plates had been implanted 20
      or 30 days before tumor injection. We established culture clones from the tumors
      arising in normal mice and mice immunosuppressed by irradiation. Clones derived
      from the tumors which had arisen in normal mice after implantation with plastic
      plates were lethal when re-implanted in normal mice (71%). On the other hand,
      clones derived from the tumors that arose in irradiated mice with or without
      plastic plates were lethal in only a few normal mice, when re-implanted (20 and
      8%, respectively). These results indicate that QR clone cell progression is
      enhanced by the early phase of inflammation at the site of plastic plate
      implantation and that the progression-enhancing activity of co-implantation with
      a plastic plate is inhibited by previous whole-body irradiation of hosts.

PMID- 8294214
TI  - Decreased dimethylnitrosamine-induced O6- and N7-methyldeoxyguanosine levels
      correlate with development and progression of lesions in rat
      hepatocarcinogenesis.
AB  - Formation and repair of O6-medG and N7-medG (O6- and N7-methyldeoxyguanosine) in
      glutathione S-transferase-P form (GST-P)-positive liver cell foci, nodules,
      primary hepatocellular carcinoma (HCC) and transplanted hepatocellular carcinoma
      (TRP) induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were
      immunohistochemically assessed following a single exposure to dimethylnitrosamine
      (DMN). Male Fischer 344 rats received a 0.1% solution of EHEN as their drinking
      water for 4 weeks and were maintained on basal diet until week 40, when a single
      50 mg/kg body weight dose of DMN was administered intraperitoneally. Nude rats
      (NIH rnu/rnu) bearing TRP were similarly treated. Sequential killing 6, 12, 24,
      48 and 72 h thereafter revealed significantly decreased indices of cells binding
      antibodies to O6-medG and N7-medG adducts in GST-P-positive foci and nodules, and
      particularly HCC and TRP, as compared to background parenchyma values. Similarly,
      differences between foci/nodules and HCC/TRP were also significant, indicating
      that decrease in adduct formation is associated with further malignant
      conversion. The rate of DNA adduct repair in foci and nodules subsequent to the
      peak found at the 12 h time-point did not appear to be significantly different
      from that in the surrounding tissue at the dose of DMN studied. The results
      indicate decreased formation of DMN-associated DNA damage, in line with the known
      metabolic profile of carcinogen-induced focal liver lesions.

PMID- 8294215
TI  - Three-dimensional analysis of glutathione S-transferase placental form-positive
      lesion development in early stages of rat hepatocarcinogenesis.
AB  - The development of glutathione S-transferase placental form (GST-P)-positive
      lesions in the rat liver, from single cells to foci, and their locations within
      liver lobules were examined by a combined stereological approach for calculation
      of three-dimensional (3-D) data and by 3-D computer graphics for reconstruction
      of lesions. Two weeks after initiation with diethylnitrosamine, the rats were
      divided into two groups. Animals in group 1 were given 2-acetylaminofluorene, and
      animals in group 2 were given basal diet for 6 weeks. Partial hepatectomy (PH)
      was performed at week 3. The GST-P-positive single cells increased in number per
      liver after PH in group 1, but not in group 2, where a plateau level was
      maintained. The number of GST-P-positive foci per liver in group 2 also reached
      an almost constant low value after 4 weeks. In contrast, foci in group 1
      increased greatly after PH. A 3-D reconstruction, performed with a computer
      graphics system using up to 180 sections at 10 microns intervals, revealed the
      single cells to be distributed at random. Those that grew into foci were also not
      preferentially localized in any particular zone of the hepatic lobule. When foci
      within the same lobule came into contact, they underwent fusion. The present
      results thus indicate that only a small proportion of GST-P-positive single cells
      develops into foci, and that their growth is independent of zonal factors within
      individual lobules in early stages of rat hepatocarcinogenesis.

PMID- 8294216
TI  - Induction of glandular stomach cancers in C3H mice treated with N-methyl-N
      nitrosourea in the drinking water.
AB  - Establishment of an animal model of stomach carcinogenesis in mice was attempted
      using N-methyl-N-nitrosourea (MNU) in the drinking water. One hundred and forty
      eight male 6-week-old C3H mice were given MNU in their drinking water at a
      concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group 3) or 0 ppm
      (group 4) for 30 weeks. At the end of this time, dose-related induction of
      adenomatous hyperplasias was found. From weeks 31 to 54 adenocarcinomas developed
      in a dose-dependent manner in groups 1, 2 and 3. In total, 6 well differentiated
      and 5 poorly differentiated adenocarcinomas as well as 6 signet ring cell
      carcinomas arose in 15 stomach cancer-bearing animals in group 1, 4 well
      differentiated and 2 poorly differentiated adenocarcinomas with one signet ring
      cell carcinoma in 5 mice of group 2 and one well differentiated adenocarcinoma in
      group 3. In the forestomach, only one squamous cell carcinoma was found at week
      54 in group 1 along with a single well differentiated adenocarcinoma in the
      duodenum. Thus, MNU in the drinking water selectively induced neoplastic lesions
      in the glandular stomach epithelium of mice.

PMID- 8294217
TI  - Transmission routes of HTLV-I: an analysis of 66 families.
AB  - HTLV-I transmission routes were found for 66 carrier pregnant women by studying
      sera, from the carrier pregnant women, their mothers, and their husbands, and by
      obtaining detailed family histories at interview. Forty-one cases (62.1%) were
      considered to be instances of vertical transmission, 15 (22.8%) of sexual
      transmission, 6 (9.1%) of blood transfusion, and 4 (6.1%) undecided. To date,
      most cases of adult T-cell leukemia (ATL) have been considered to result from
      vertical transmission. Our results therefore imply that about 30% (22.8% + 9.1%)
      of the carrier pregnant women are at minimal risk of ATL. Moreover, in case of
      presumed husband-to-wife transmission, more than half (6/11) were infected
      between one year and four years after marriage.

PMID- 8294218
TI  - Presence of a regulatory element within the first intron of the human platelet
      derived growth factor-A chain gene.
AB  - We detected a suppressive element in the first intron of the human platelet
      derived growth factor A chain (PDGF-A) gene. Two or more proteins, at least 110
      kd and 90-kd proteins, were bound over a wide region of this fragment, and the
      fragment suppressed the expression of the PDGF-A chain via these proteins in
      vivo. Since the fragment also had suppressor activity on the promoter of the PDGF
      B chain, it may be involved in a suppressive mechanism of gene expression common
      to PDGF-A and -B chains. Four tandem repeats of CCCCAT(CCCC) and three direct
      repeats of GGGGAG were observed in this region. The expression of the PDGF-A
      chain is considered to be regulated by a mechanism involving not only the 5'
      upstream region but also introns.

PMID- 8294219
TI  - Telomere change and loss of heterozygosity of mouse primary tumors and cell
      lines.
AB  - Changes in the number of telomere repeat arrays were examined in mouse tumor
      cells. Telomeres that function for the protection of chromosomes were detected as
      bands and a smear by pulsed field gel electrophoresis and gel-hybridization using
      (TTAGGG)4, as a probe. Of eight primary tumors induced in F1 mice between C57BL/6
      and C3H/He and between C57BL/6 and MSM, three showed telomere alteration, two
      having extra bands and one having lost several telomere bands. The others
      exhibited patterns similar to those of normal tissues. However, the change was
      detected in all four cell lines that were established from one of the tumors. One
      cell line was further cloned and examined. Two of the nine clones differed in the
      telomere pattern. The telomere change was also observed in two other cell lines,
      FM3A cells and nontransformed BALB3T3 cells. These results suggest that telomeres
      are highly mutable in tumor cells and cultured cell lines. Three of the tumors
      and one cell line were analyzed for loss of heterozygosity with 51 microsatellite
      probes covering all 19 autosomes. Also, karyotype analysis of the cell line was
      performed. No allelic loss was seen and chromosomal abnormality was rare,
      although aneuploidy and imbalance in chromosomal number were observed. Possible
      involvement of the telomere changes observed here in chromosome impairment is
      discussed.

PMID- 8294220
TI  - Progression of androgen-sensitive mouse tumor (Shionogi carcinoma 115) to
      androgen-insensitive tumor after long-term removal of testosterone.
AB  - Shionogi Carcinoma 115 (SC115) is an androgen-sensitive transplantable mouse
      tumor. To study the mode of progression from androgen-sensitive to -insensitive
      tumor, cloned SC115 cells were serially cultured without androgen. Shortly after
      withdrawal of androgen, SC115 cells showed markedly decreased growth, but growth
      resumed gradually with loss of response to androgen and the cells 60 weeks after
      androgen removal [A(-)60 cells] grew faster than SC115 cells cultured in the
      presence of androgen. A(-)60 cells showed malignant phenotype with morphological
      changes and tumorigenicity in male and female mice. Although mRNA and binding
      capacity of androgen receptor were maintained, the cells after removal of
      androgen rapidly lost expression of mouse mammary tumor virus-related gene and
      the loss was irreversible in A(-)60 cells. The stimulating effect of basic
      fibroblast growth factor (bFGF) temporarily decreased, then recovered to the
      initial level after long-term androgen removal. This fluctuation of response to
      bFGF was accompanied with changes in the number of bFGF receptors and amount of
      bFGF-like substance(s) secreted. The substance(s) seemed to be an FGF-like growth
      factor different from known factors. It was concluded that progression of SC115
      cells to androgen-insensitive ones under an androgen-deprived condition proceeded
      with adaptation by means of increases in production of an FGF-like growth factor
      and in binding capacity to this factor.

PMID- 8294221
TI  - Functional analysis of mononuclear cells infiltrating into tumors: establishment
      of T cell hybridomas exhibiting distinct interacting abilities with endothelial
      cells and extracellular matrix components.
AB  - We have established eleven T cell hybridoma cell lines to investigate mechanisms
      controlling interaction of T lymphocytes with endothelial cells as well as
      extracellular matrix (ECM) proteins at the clonal level. T cell hybridomas were
      characterized and subdivided into four groups on the basis of their interaction
      behavior with high endothelial venules (HEV). Group 1 (G1) exhibited strong
      adhesiveness. The binding was temperature- and divalent cation-dependent. Group 2
      exhibited both adhesiveness and transendothelial migration (TEM, i.e.,
      transmigration beneath the cytoplasm of endothelial cells). Group 3 exhibited
      strong TEM. G2 and G3 hybridomas exhibited temperature-independent and divalent
      cation-independent binding to HEV. Group 4 exhibited nonspecific adhesiveness to
      the surface of a slide glass. BW 5147, a parent of T cell hybridomas, was
      classified as G4. TEM was dependent on both the nature of T cell hybridomas and
      endothelial cells. TEM was completely temperature-dependent. TEM of G3 hybridomas
      was not divalent cation-dependent. Each group of T cell hybridomas interacted
      with various ECM components.

PMID- 8294222
TI  - In vitro evaluation of sperm quality: an opinion.

PMID- 8294223
TI  - Treatment of idiopathic erectile dysfunction in men with the opiate antagonist
      naltrexone--a double-blind study.
AB  - Opiate antagonists can indirectly stimulate the secretion of luteinizing hormone
      (LH) and testosterone, as well as sexual functions in animals and humans. We
      therefore treated 20 otherwise healthy men with idiopathic erectile dysfunction
      aged 46.3 +/- 2.7 years (mean +/- SE, range 23.9-63.3) in a double-blind study
      with an opiate antagonist, naltrexone, or placebo. The erectile dysfunction of
      these men had persisted for 3.6 +/- 0.5 years despite libido maintenance;
      standard procedures had excluded any organic causes. Trial duration was 12 weeks
      overall. After a 4-week forerun, the patients received at first 25 mg
      naltrexone/day orally or placebo for 4 weeks followed by 4 weeks of a 50-mg dose
      of naltrexone/day or placebo. Each day the patients filled out a questionnaire
      detailing libido, degree of erection, frequency of sexual intercourse, and
      spontaneous morning erections. Serum concentrations of gonadotropins and
      testosterone were determined radioimmunologically in the initial stage and at the
      end of each phase. Both patient collectives had similar initial factors. The
      group treated with naltrexone showed a significant rise in spontaneous early
      morning erections during the treatment: from 2.8 +/- 0.3 to 4.2 +/- 0.3 a week (P
      < 0.001). The placebo group showed no significant change in spontaneous erections
      (2.4 +/- 0.3 and 2.6 +/- 0.3, respectively). The subjective parameters, however,
      such as libido, degree of erection, and frequency of sexual intercourse showed no
      significant difference within each group. There was no difference in LH, follicle
      stimulating hormone, or testosterone concentrations in both groups. Thus,
      treatment with naltrexone significantly raises the rate of spontaneous early
      morning erections when compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294224
TI  - 150-kDa proteins in dog serum bind 1.5-kDa growth-promoting factors for androgen
      independent canine prostatic epithelial cells.
AB  - Fractions obtained by gel filtration or ultrafiltration of dog serum were tested
      for their mitogenic activity on canine prostatic epithelial cells: two prostatic
      growth factor (PGF) entities were found, a major one of 150 kDa (PGF-I) and a
      minor one of 1.5-2.0 kDa (PGF-II). Treatment and/or extraction with acetic acid,
      hydrochloric acid, or acidified-ethanol or preparations enriched in PGF-I
      obtained either by ion-exchange chromatography, acetone precipitation, or
      retention by ultrafiltration membrane (cut-off 30 kDa) resulted, upon gel
      filtration, in the detection of a mitogenic activity eluting mainly at the
      position of PGF-II. Acid hydrolysis and proteolysis of PGF-II led to a loss of
      activity. It is proposed that, in dog serum, mitogenic peptides for prostatic
      epithelial cells of 1.5 kDa (PGF-II) are found in their free form and/or in
      association with proteins of 150 kDa (PGF-I).

PMID- 8294225
TI  - Inhibition of steroidogenesis in neonatal Leydig cells by unknown factor(s)
      present in spent media of androgen-treated cultured testicular cells from adult
      rats.
AB  - Treatment of cultured testicular cells from adult rats with 5 alpha
      dihydrotestosterone (DHT; 10(-6) M) or the synthetic androgen methyltrienolone
      (R1881; 10(-6) M) inhibited Leydig cell 3 beta-hydroxysteroid dehydrogenase/delta
      5-4 isomerase (3 beta-HSD) enzyme activity, whereas no effect of both androgens
      on cultured cells derived from neonatal animals could be observed. The inhibitory
      effect of DHT or R1881 on Leydig cell 3 beta-HSD enzyme activity, however, was
      abolished when adult cells were cultured in the presence of the anti-androgen
      cyproterone acetate (CPA; 10(-6) M) or the protein synthesis inhibitor
      cycloheximide (CX; 1 microgram/ml). Testicular cells from adult animals were also
      cultured in the presence of the different treatments described above, and the
      spent media was collected and thereafter used as conditioned culture medium (CCM)
      in subsequent experiments performed with neonatal cells. Dispersed testicular
      cells from neonatal rats were cultured for 12 days in McCoy's 5a medium of in CCM
      derived from R1881-treated adult cells, and fresh culture medium or CCM was
      replaced every 2 days. The human chorionic gonadotropin (hCG)-stimulated
      testosterone production of neonatal cells was abolished in the presence of CCM
      derived from R1881-treated adult cells. Nevertheless, the steroidogenic response
      to hCG recovered when neonatal cells were cultured for two additional days in
      McCoy's 5a medium. Treatment of neonatal cells with increasing concentrations of
      hCG (0.1-10 ng/ml) resulted in a dose-dependent augmentation in Leydig cell 3
      beta-HSD enzyme activity and testosterone production.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8294226
TI  - Synthesis of docosahexaenoyl coenzyme A in human spermatozoa.
AB  - The synthesis of docosahexaenoyl coenzyme A (22:6-CoA) was studied in a long
      chain fatty acid: CoASH ligase (AMP)-enriched fraction from human spermatozoa and
      was compared to palmitoyl CoA (16:0-CoA) synthesis. The pH optimum for 22:6
      activation was 8.4, which was identical to the value obtained with 16:0. The Km
      for ATP was 0.5 mM when 22:6 was the acyl substrate; however, when 16:0 was
      incubated with the ligase preparation, the Km for ATP was 2.9 mM. When CoASH was
      varied and 22:6 was the fatty acyl acceptor, a pattern of negative cooperatively
      was observed. This was confirmed by a downwardly concave double-reciprocal plot,
      a Hill coefficient of 0.63, and an Rs in excess of 150. The Hill coefficient with
      16:0 and CoASH was 0.94. Palmitic acid was demonstrated to be a competitive
      inhibitor of 22:6-CoA synthesis. Based upon these data, we conclude that the
      kinetics of spermatozoan ligase are complex, and, in addition, these data support
      the hypothesis that 22:6 may regulate ligase activity, and therefore free fatty
      acid utilization, in sperm.

PMID- 8294227
TI  - Isolation and characterization of mitochondria from turkey spermatozoa.
AB  - A procedure was developed to rapidly isolate functional, intact mitochondria from
      turkey spermatozoa. Semen was collected from turkeys, pooled, and centrifuged to
      remove spermiophages and other cells. The sperm cells were then mechanically
      disrupted with a Dounce homogenizer, sonicated, and centrifuged using a
      discontinuous Percoll gradient. Electron microscopy revealed morphologically
      intact mitochondria. The isolated mitochondria exhibited cytochrome oxidase
      activity, oxygen consumption, and were stained by rhodamine 123, a fluorescent
      stain specific for functional mitochondria in eukaryotic cells. Mitochondrial DNA
      (mtDNA) was isolated and purified, and the genome was determined to be 16.457 +/-
      0.07 kbp. Restriction fragment patterns were identified using the endonucleases
      EcoR1, HindIII, and BamH1. Mitochondrial DNA was also purified from turkey liver
      and testis, and no differences in the restriction enzyme patterns were found
      between somatic and germ cell mtDNA. It is concluded that mitochondria can be
      isolated from spermatozoa for metabolic or genetic study.

PMID- 8294228
TI  - Identification and localization of copper-zinc superoxide dismutase gene
      expression in rat testicular development.
AB  - Reactive oxygen species are highly toxic agents that appear to have an important
      role in male infertility. In order to understand the potential for the testis to
      be protected from reactive oxygen, the mRNA levels of the natural reactive oxygen
      scavenger, copper-zinc superoxide dismutase (SOD), were determined in testes and
      other organs in rats using northern analysis and in situ hybridization. Northern
      analysis of total RNA from organs of 60-day-old rats demonstrated an SOD mRNA
      with a transcript length of 0.77 kb; its concentration was highest in the kidney,
      liver, testis, and epididymis. In testis, northern analysis of total RNA
      demonstrated two mRNA transcripts of 0.77 kb and 0.94 kb. The concentrations of
      the 0.77-kb transcript varied only slightly between 10 and 100 days of age. In
      contrast, the 0.94-kb transcript became detectable by northern analysis between
      30 and 40 days of age, then its concentration rose progressively to peak at 60
      days. In situ hybridization studies demonstrated a uniform distribution of SOD
      mRNA within seminiferous tubules of prepubertal rats at 10 days of age and a
      heterogeneous, stage-specific pattern in older animals. In mature rats, the
      highest level of SOD mRNA was detected in tubules just prior to spermiation
      (stages VI-VIII). In conclusion, two SOD mRNA transcripts were identified in the
      rat testes that followed significantly different patterns of expression during
      development. In situ hybridization studies revealed that accumulation of the SOD
      mRNA in the seminiferous tubule was stage specific. These data suggest that SOD
      may play an important role during testicular development and spermatogenesis in
      rats.

PMID- 8294229
TI  - Neonatal goitrogen treatment increases adult testis size and sperm production in
      the mouse.
AB  - Male rats made hypothyroid during neonatal life show unprecedented increases in
      adult testis size and daily sperm production (DSP). To determine if this effect
      was unique to the rat or could also be demonstrated in other species, we examined
      the effects of neonatal treatment with the reversible goitrogen 6-propyl-2
      thiouracil (PTU) on adult testis size and function in the mouse. Male Swiss
      Webster mice were untreated (control) or given PTU by adding 0.1% (w/v) to their
      mother's water from birth to day 25 postpartum. All pups were then weaned and
      given no further treatment. Sertoli cell proliferation was examined using
      tritiated thymidine autoradiography in some control and treated mice at 0, 5, 10,
      15, 20, and 25 days, while the remainder were killed at 90 days to determine a
      variety of reproductive parameters. Neonatal PTU treatment decreased growth; body
      weight of treated mice at 4 weeks of age was 57% less than controls. Treated mice
      grew rapidly following cessation of PTU treatment, although their weights never
      equalled controls, remaining 17% smaller at 90 days of age. At 90 days of age,
      testis weight and DSP were increased by approximately 30% and 50%, respectively,
      in PTU-treated mice compared to controls. Despite the increased testis weight and
      function, serum testosterone concentrations were not different in control and
      treated mice. Testicular and epididymal histology in treated mice was similar to
      controls, while epididymal sperm in treated mice were motile and morphologically
      normal. Sertoli cell proliferation was altered in treated mice.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8294230
TI  - The nuclear status of human sperm cells by TEM image cytometry: nuclear shape and
      chromatin texture in semen samples from fertile and infertile men.
AB  - Changes in nuclear size, shape, and chromatin texture during spermiogenesis and
      epididymal transport of human sperm were recently analyzed using transmission
      electron microscopy (TEM) image cytometry followed by multivariate statistical
      analysis of data. In the present study, this same methodology was used to
      investigate the nuclear morphology of spermatozoa in semen samples from fertile
      and infertile men. Analysis was carried out on a large series of micrographs of
      sections of sperm nuclei from a donor group with proven fertility and from a
      patient group with a mean infertility duration of 10 years with no obvious male
      or female infertility factors (only a slight decrease in the proportion of sperm
      heads with normal morphology was noted in routine semen tests). For the patient
      group, it was found that nuclei had a significantly less flattened shape (i.e.,
      increased roundness as a consequence of increased thickness and decreased
      length). Furthermore, significant differences between donor and patient groups
      were found for most parameters of chromatin texture. In the patient group,
      chromatin was less condensed, and there was more homogeneous distribution of the
      different degrees of chromatin condensation. In addition, the organization of
      chromatin condensation and distribution along the major axis of the nucleus was
      found to be significantly different in the two groups. Stepwise linear
      discriminant analysis indicated a good classification rate of only 66% for nuclei
      of patients when using the eight major nuclear parameters, thus indicating the
      striking heterogeneity of nuclear morphology for both patient and donor
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294231
TI  - Relationship of semen quality, number of sperm inseminated, and fertility in
      rabbits.
AB  - The relationship between the total number of sperm inseminated, semen quality,
      and fertility in rabbits was investigated, using fractionated or unfractionated
      semen and different diluting fluids. Semen was from Dutch-belted males collected
      twice weekly with an artificial vagina. All does were superovulated except in
      Experiment 3. In Experiment 1, sperm were fractionated on discontinuous 4% and
      10% bovine serum albumin columns. Sperm from each portion of the gradient, along
      with unfractionated controls, were diluted to give 0.25 x 10(6), 0.5 x 10(6), 1.0
      x 10(6), and 2.0 x 10(6) total sperm per insemination. In Experiment 2, sperm
      were diluted with Dulbecco's phosphate-buffered saline to provide 0.10 x 10(6),
      0.50 x 10(6), and 1.0 x 10(6) total sperm per insemination, with minimal
      processing time. In Experiment 3, does were allowed to kindle after inseminating
      0.1 x 10(6) or 1.0 x 10(6) sperm. In Experiment 4, sperm were diluted with TALP
      buffer: seminal plasma 1:1 to 0.025 x 10(6), 0.05 x 10(6), and 0.10 x 10(6) total
      sperm per insemination. Over 2,800 embryos or unfertilized oocytes were obtained
      either 24 or 48 hours after insemination to measure fertility. Sperm numbers
      required for normal fertility were 0.50 x 10(6) in Experiment 1 and only 0.05 x
      10(6) in Experiment 4. This reduction presumably was due primarily to reduced
      processing time and diluent change. Litter size was normal with 0.1 x 10(6) sperm
      (Experiment 3). In Experiment 4, computer-assisted sperm analysis (HTM 2030
      system; Beverly, Massachusetts) was adapted to successfully screen out some of
      the "interfering" granules in rabbit semen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294232
TI  - Effect of cryoprotective additives and cryopreservation protocol on sperm
      membrane lipid peroxidation and recovery of motile human sperm.
AB  - Sperm membrane damage during cryopreservation reduces the recovery of motile
      sperm. The present study investigates changes in sperm motility and membrane
      lipid peroxidation (LPO) in response to two changes in the standard sperm
      cryopreservation/thawing methodology: 1) the addition of platelet-activating
      factor (PAF) and pentoxifylline (PTX) as cryoprotective additives, and 2) the
      alteration of sample thawing time. PAF (1 microM) and PTX (3 mM) were added to
      fresh sperm samples prior to cryopreservation. After 2 weeks the samples were
      thawed either quickly (5 minutes at 37 degrees C) or slowly (30 minutes at 4
      degrees C) and evaluated for sperm motility and LPO. Thawing time influenced both
      post-thaw motility and LPO. Samples thawed quickly exhibited a 31% increase in
      motility recovery (35.2 +/- 4.3% in quick-thaw samples; 24.3 +/- 3.9% in slow
      thaw samples) and a 23% lower LPO level (23.3 +/- 3.4% in quick-thaw samples;
      30.09 +/- 4.4% in slow-thaw samples) compared to samples thawed slowly. Results
      also demonstrated that PAF (49 +/- 1.7%) or PTX (42.6 +/- 1.5%) enhance post-thaw
      motility in comparison to control (35.8 +/- 1.2%), whereas neither PAF nor PTX
      affect post-thaw LPO (19.1 +/- 2.2% in controls; 20.2 +/- 1.7% in PAF samples;
      20.5 +/- 1.4% in PTX samples). These results support observations that there is a
      negative correlation between sperm motility and LPO in cryopreserved samples. The
      results also discount the hypothesis that LPO protection is a result of the
      cryoprotective action of PAF or PTX.

PMID- 8294233
TI  - MS-347a, a new inhibitor of myosin light chain kinase from Aspergillus sp.
      KY52178.
AB  - MS-347a was isolated from the culture broths of Aspergillus sp. KY52178 as an
      inhibitor of smooth muscle myosin light chain kinase (MLCK). MS-347a inhibited
      the activity of chicken gizzard MLCK with an IC50 value of 9.2 microM. The
      inhibition was dependent on time of preincubation of MS-347a with the enzyme,
      suggesting irreversible inhibition. It is likely that the inhibitor binds to the
      catalytic domain of MLCK, since the compound inhibited not only calmodulin
      dependent but also calmodulin-independent activity of MLCK. Calmodulin-dependent
      cyclic nucleotide phosphodiesterase, cAMP-dependent protein kinase and cGMP
      dependent protein kinase were not inhibited by 150 microM MS-347a at all,
      although the compound inhibited protein kinase C with an IC50 value of 16 microM.
      MS-347b, a minor component was also isolated from the same culture broths. This
      minor component at 150 microM did not inhibit the activity of MLCK.

PMID- 8294234
TI  - Lateritin, a new inhibitor of acyl-CoA:cholesterol acyltransferase produced by
      Gibberella lateritium IFO 7188.
AB  - A new inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), designated
      lateritin, was isolated from the mycelial cake of Gibberella lateritium IFO 7188
      by successive purification procedure of solvent extraction, silica gel column
      chromatography and reverse phase HPLC. Spectroscopic analyses of the compound
      yielded 4-methyl-6-(1-methylethyl)-3-phenylmethyl-1,4-perhydrooxazine-2,5- dione
      as the proposed structure. Lateritin inhibited rat liver ACAT activity by 50% at
      a concentration of 5.7 microM. This inhibition was time-dependent and
      irreversible.

PMID- 8294235
TI  - FR901459, a novel immunosuppressant isolated from Stachybotrys chartarum No.
      19392. Taxonomy of the producing organism, fermentation, isolation, physico
      chemical properties and biological activities.
AB  - FR901459, a novel immunosuppressant, has been isolated from the fermentation
      broth of Stachybotrys chartarum No. 19392. The molecular formula of FR901459 was
      determined as C62H111N11O13. FR901459 was found to be a member of the cyclosporin
      family. However, it is structurally distinct from any other cyclosporins
      discovered so far, in that Leu is present at position 5 instead of Val. FR901459
      was capable of prolonging the survival time of skin allografts in rats with one
      third the potency of cyclosporin A.

PMID- 8294236
TI  - A new antitumor substance, BE-18591, produced by a streptomycete. I.
      Fermentation, isolation, physico-chemical and biological properties.
AB  - New antitumor substance, designated BE-18591, was isolated from the culture broth
      of a streptomycete, strain BA18591. The active principle was extracted from
      mycelium by methanol and purified by silica gel chromatography. BE-18591
      inhibited the growth of MKN-45 human stomach cancer cell line as well as P388
      cell line. In in vivo experiments, BE-18591 inhibited the growth of Ehrlich
      ascites tumor.BE-18591 showed antimicrobial activity against Gram-positive and
      some Gram-negative bacteria.

PMID- 8294237
TI  - New antiviral antibiotics, kistamicins A and B. I. Taxonomy, production,
      isolation, physico-chemical properties and biological activities.
AB  - A new strain of Microtetraspora parvosata subsp. kistnae subsp. nov. (ATCC 55076)
      was found to produce new antiviral antibiotics, designated kistamicins A and B.
      These antibiotics exhibited activity against influenza virus type A and moderate
      activity against Gram-positive bacteria.

PMID- 8294238
TI  - New antiviral antibiotics, kistamicins A and B. II. Structure determination.
AB  - The structures of antiviral antibiotics kistamicins A and B have been determined
      by a combination of chemical degradation and spectral analysis. They are commonly
      composed of D-tyrosine, 3,5-dihydrophenylglycine, a biphenyl ether bis-amino
      acid, and a diphenyl substituted indole tris-amino acid, forming a tricyclic ring
      structure. Kistamicin B possessed a phenethylamide at the amino terminal of
      kistamicin A. They are structurally related to the nuclei of the vancomycin group
      antibiotics particularly to antibiotic complestatin.

PMID- 8294239
TI  - A novel quinone antibiotic from Malbranchea cinnamomea TAIM 13T54.
AB  - A novel quinone antibiotic named malbranicin was isolated from the culture
      filtrate and mycelium of Malbranchea cinnamomea TAIM 13T54, a thermophilic
      fungus. The antibiotic was elucidated to be 6-(1-acetylethyl)-2-methoxy-2,5
      cyclohexadiene-1,4-dione by spectral analysis. Malbranicin exhibited
      antimicrobial and cytotoxic activities against Gram-positive bacteria and
      mammalian cell lines, respectively.

PMID- 8294240
TI  - Isolation, structure determination and biological activities of a novel
      antifungal antibiotic, S-632-C, closely related to glutarimide antibiotics.
AB  - A new antifungal antibiotic, S-632-C, was extracted with ethyl acetate from the
      culture filtrate of Streptomyces hygroscopicus S-632 and isolated through a
      combination of column and preparative thin-layer chromatographies on silica gel.
      The structure of S-632-C was determined by analysis of 1H and 13C-NMR, MS, UV and
      IR spectra in comparison with those of S-632-A2 (9-methylstreptimidone). The
      signals were assigned on the basis of 2D NMR experiments, which involved 1H-1H
      DQF COSY, HMQC and HMBC spectral analysis. From these results, the chemical
      structure of S-632-C was elucidated as 6-(3,5-dimethyl-2-oxo-4,6-octadienyl)-4
      carbamoylmethyl-3,4, 5,6-tetrahydro-2- pyrone. The antibiotic exhibited
      exclusively weak in vitro antifungal activity against Saccharomyces spp. and
      similar cytotoxic activity against KB carcinoma cells, as compared with the
      glutarimide antibiotic S-632-A2. In addition, this antibiotic had the ability to
      change the morphology of ras(ts)-transformed NRK cells to that of normal cells,
      also a characteristic S-632-A2 and B1.

PMID- 8294241
TI  - Thiomarinol, a new hybrid antimicrobial antibiotic produced by a marine
      bacterium. Fermentation, isolation, structure, and antimicrobial activity.
AB  - Thiomarinol, an antimicrobial antibiotic, was isolated from the culture broth of
      a marine bacterium, Alteromonas rava sp. nov. SANK 73390. Its structure was
      deduced as a hybrid composed of a pseudomonic acid analogue and holothin by NMR
      spectral analysis and chemical degradation. Antimicrobial activity against Gram
      positive and Gram-negative bacteria of thiomarinol was stronger than both of
      pseudomonic acids and pyrrothine antibiotics.

PMID- 8294242
TI  - AB5046A and B, novel chlorosis-inducing substances from Nodulisporium sp.
AB  - Novel chlorosis-inducing substances, AB5046A and B, were isolated from the
      culture broth of a fungal strain. The producing organism, designated AB5046, was
      identified as a member of Nodulisporium. AB5046A and B were purified by
      extraction with EtOAc and silica gel chromatography. The structure of AB5046A and
      B were determined to be 2-butyryl-3,5-dihydroxy-cyclohex-2-ene-1-one and 2-acetyl
      3,5-dihydroxy-cyclohex-2-ene-1-one, respectively, by spectroscopic analyses.
      AB5046A and B induced chlorosis against Japanese barnyard millet in vitro. The
      chlorosis activity of these compounds was stronger against monocotyledons than
      dicotyledons.

PMID- 8294243
TI  - Hynapenes A, B and C, new anticoccidial agents produced by Penicillium sp. I.
      Production, isolation and physico-chemical and biological properties.
AB  - Penicillium sp. FO-1611, a soil isolate, was found to produce a series of new
      anticoccidial compounds. Three active compounds, designated hynapenes A, B and C,
      were isolated from the fermentation broth of the producing strain by solvent
      extraction, silica gel column chromatography, gel filtration on Sephadex LH-20
      and preparative HPLC. Hynapenes inhibited the growth of Eimeria tenella in an in
      vitro assay using BHK-21 cells as a host. No schizont in the cells was observed
      at concentrations ranging above 123 microM, 34.7 microM and 34.7 microM for
      hynapenes A, B and C, respectively.

PMID- 8294244
TI  - Hynapenes A, B and C, new anticoccidial agents produced by Penicillium sp. II.
      Structure elucidation.
AB  - The structures of hynapenes A, B and C, novel anticoccidial agents, were
      determined by spectroscopic analyses. Hynapenes A, B and C were deduced to be
      (2E,4E)-5-(1,3,4-trihydroxy-2,6,8-trimethyldecalin)-2,4-p entadienoic acid,
      (2E,4E)-5-(1-ene-3-oxo-2,6,8-trimethyldecalin)-2,4-pentad ienoic acid and (2E,4E)
      5-(3-ene-1-oxo-2,6,8-trimethyldecalin)-2,2,4-pent adienoic acid, respectively.

PMID- 8294245
TI  - In vitro and ex vivo free radical scavenging activities of carazostatin,
      carbazomycin B and their derivatives.
AB  - Free radical scavenging activities of various carbazole compounds, carazostatin,
      carbazomycin B and their chemically modified derivatives were studied in vitro
      and ex vivo. Among these compounds, carazostatin, which was isolated as a free
      radical scavenger from the culture of Streptomyces chromofuscus, showed the most
      potent inhibitory activity against lipid peroxidation of rat brain homogenate in
      vitro. Carbazomycin B, a known antimicrobial antibiotic, also exhibited strong
      activity in this system. Although O-modified derivatives of carazostatin and
      carbazomycin B retained considerable activity, N,O-dimethyl derivatives did not
      suppress the peroxidation. On the other hand, the results from the ex vivo
      evaluation of these carbazoles in the lipid peroxidation system of mouse blood
      plasma showed that the original compounds as well as their O-modified derivatives
      had a strong inhibitory activity upon oral administration to mice. These findings
      suggest that these natural carbazoles and their effective derivatives can protect
      tissues from the peroxidative damage due to generation of free radicals.

PMID- 8294246
TI  - Heteroaryliumthio substituted carbapenem derivatives: synthesis and in vitro
      activity of 1 beta-methyl-2-(dihydropyrrolotriazoliumthio)carbapenems.
AB  - The syntheses of five thiols, including three dihydropyrrolotriazoliumthiol
      salts, 1,4-dimethyl-5-mercaptomethyl-1,2,4-triazolium trifluoromethanesulfonate,
      and 6-mercapto-6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazolium chloride; and the
      addition of these thiols to 4-nitrobenzyl (1R,5R,6S)-2-(diphenylphosphono)oxy-6
      [1(R)-hydroxyethyl]-1-met hylcarbapen-2-em-3-carboxylate and the subsequent
      hydrogenolysis of the addition products is described. The latter thiol provides a
      new route towards the preparation of L-627 (LJC 10,627). The compounds were
      evaluated in vitro against a panel of Gram-positive and Gram-negative bacteria
      and their antibacterial activities compared with imipenem. The compounds were
      measured for their hydrolytic stability to dehydropeptidase I (DHP-I) relative to
      imipenem. The five compounds generally had poorer Gram-positive and Pseudomonas
      activity than imipenem, although their Gram-negative activity was variably
      improved. The monocyclic triazolium analog was nearly comparable in overall
      activity to the four bicyclic heterarylium analogs evaluated, including L-627
      (LJC 10,627). All compounds were more stable to DHP-I than imipenem, although
      minor differences existed among them.

PMID- 8294247
TI  - Synthesis of 3-episiastatin B analogues having anti-influenza virus activity.
AB  - Two epimers of siastatin B, 3-episiastatin B (3) and 3,4-diepisiastatin B (4),
      were obtained by the chemical modification of siastatin B. Compound 3 showed
      marked inhibitory activity against influenza virus neuraminidases and significant
      inhibition of influenza virus infection in vitro.

PMID- 8294248
TI  - Napyradiomycins A and B1: non-steroidal estrogen-receptor antagonists produced by
      a Streptomyces.

PMID- 8294249
TI  - A new antitumor substance, BE-18591, produced by a streptomycete. II. Structure
      determination.

PMID- 8294250
TI  - The synthesis and biological characteristics of new orally active cephems.

PMID- 8294251
TI  - WS9761 A and B: new non-steroidal androgen-receptor antagonists produced by a
      Streptomyces.

PMID- 8294252
TI  - Nisamycin, a new manumycin group antibiotic from Streptomyces sp. K106.

PMID- 8294254
TI  - Isolation and characterization of a new antibiotic, malolactomycin A.

PMID- 8294253
TI  - Isochromophilones I and II, novel inhibitors against gp120-CD4 binding from
      Penicillium sp.

PMID- 8294255
TI  - Biochemical studies on 2-deoxy-scyllo-inosose, an early intermediate in the
      biosynthesis of 2-deoxystreptamine. IV. A clue to the similarity of 2-deoxy
      scyllo-inosose synthase to dehydroquinate synthase.

PMID- 8294256
TI  - A family of cyclophellitol analogs: synthesis and evaluation.

PMID- 8294257
TI  - Calcium and magnesium transport by isolated goldfish hair cells.
AB  - We used electron-probe analysis (EPA) to investigate the transport of the
      divalent cations calcium and magnesium across the plasma membranes of hair cells.
      Unlike ion-sensitive fluorescent dyes, EPA detects these ions regardless of the
      state of chemical combination inside the cell; changes in these cell ions
      determined by EPA indicate net transport across the cell membrane. Raising or
      lowering either extracellular divalent cation within 1 mM of its control level
      raised or lowered its cell contents, but further increases in extracellular
      concentration of either ion had little additional effect on the cell content of
      that ion. New steady-state contents could be obtained within minutes, but the net
      divalent cation currents required to account for the observed changes would have
      been smaller than most currents recorded electrophysiologically, less than 1 pA.
      The effects of replacing extracellular Na+ with other ions were consistent with
      the presence in hair cells of exchangers for divalent cations thought to occur in
      other tissues: electrically neutral sodium/magnesium exchange (2 Na+ per Mg2+)
      and electrogenic sodium/calcium exchange (at least 3 Na+ per Ca2+). The increase
      in cell Ca after 1 minute of potassium-depolarization was similar to that
      expected from electrophysiological studies of voltage-sensitive calcium currents
      in goldfish hair cells. After that time in elevated potassium, however, either
      calcium-entry pathways were inhibited or calcium-export mechanisms were enhanced.

PMID- 8294258
TI  - Extracellular N-methyl-D-glucamine leads to loss of hair-cell sodium, potassium,
      and chloride.
AB  - The organic cation N-methyl-D-glucamine (NMDG) is often used to replace
      extracellular sodium in experimental studies. Replacing 100 mM of Na+ with NMDG+
      in the fluid bathing isolated goldfish hair cells led to a rapid loss not only of
      cell sodium, but also of cell potassium and chloride. The loss of inorganic cell
      solutes was accompanied by acidification of the cells. Cell volume did not change
      significantly. These results are consistent with passage of the cationic form of
      NMDG, a titratable amine with a pKa of 9.6, across the hair-cell membrane. These
      results should have bearing in interpreting results of experiments in which this
      cation is used to replace extracellular sodium, particularly for periods of time
      longer than 3 min.

PMID- 8294259
TI  - Altered malate dehydrogenase activity in nucleus magnocellularis of the chicken
      following cochlea removal.
AB  - The metabolism of second order auditory neurons in nucleus magnocellularis (NM)
      in the chick brainstem can be profoundly altered when excitatory input from the
      cochlea is removed. Within hours of cochlea removal, NM neurons show an increase
      in histochemical staining for the Kreb's cycle enzyme succinate dehydrogenase
      (SDH), followed in several days by decreases in SDH staining. We examined the
      activity of another Kreb's cycle enzyme, malate dehydrogenase (MDH) using a
      histochemical stain and a sensitive quantitative biochemical assay for
      comparison. We found changes in MDH staining similar in time course and magnitude
      to those of SDH; within 4 h of cochlea removal, MDH activity increases in
      ipsilateral NM neurons. By 9 days after cochlea removal MDH activity decreases,
      although not to the same degree as seen with SDH. Biochemical measurements of MDH
      activity also showed an early increase in activity in ipsilateral NM, followed at
      9 days survival by a decrease in activity. Biochemical measurements of the
      activity of other enzymes in NM may be useful in further defining the metabolic
      consequences of deafferentation.

PMID- 8294260
TI  - Distortion in the cochlea: acoustic f2-f1 at low stimulus levels.
AB  - The stimulus level and frequency dependence of the quadratic difference tone
      (QDT) measured as an otoacoustic emission in the ear canal has been investigated
      in the guinea pig and compared with simultaneously measured cubic difference tone
      (CDT) and with the round window electrical response. Acoustic QDT level tended to
      be highly labile. Growth of the ear canal response with covaried stimuli was very
      gradual (slope < 0.5). Acoustic and CM responses showed similar behaviour when f2
      alone was incremented. The QDT was strongly dependent on stimulus frequency
      separation for high frequency stimuli. It is suggested that, at low stimulus
      levels and high frequencies, the acoustic QDT may originate in the 'tonic' motile
      responses of outer hair cells as they follow the envelope of the two-tone
      stimulus.

PMID- 8294261
TI  - Osmotic pump implant for chronic infusion of drugs into the inner ear.
AB  - Continuous long-term delivery of experimental drugs to the cochlea of a small
      animal, such as a young guinea pig, presents several technical problems. A method
      of placing and securing a cannula-osmotic pump system is described in this paper.
      Guinea pigs (225-410 g) were unilaterally implanted with an Alzet micro-pump and
      cannula for delivery of 20 mM tetrodotoxin (TTX) (six animals) or saline (three
      animals) for three days (1 microliter/h). Auditory brainstem responses (ABRs)
      were recorded under light anesthesia on post-implant day 1 and day 3 and compared
      with pre-implant baseline values. In all six cochleas infused with TTX, most
      frequencies showed a 30-60dB decrease in sensitivity within 24 h. Saline control
      animals showed little or no change from baseline sensitivity for most
      frequencies. In three TTX-infused animals, the cannula-pump unit was removed on
      day 3, and ABRs were followed during recovery. Most frequencies returned to, or
      near, pre-implant levels after pump removal but recovery times varied. By day 6,
      all animals had recovered post-surgical weight loss and showed a gain of 10-40 g.
      Brains and cochleas were removed and processed for sectioning. Assessment of the
      cochlear nucleus of non-recovery TTX-treated animals showed a deafness-related
      flattening of auditory nerve active zones on the treated side.

PMID- 8294262
TI  - Input from the inferior colliculus to medial olivocochlear neurons in the rat: a
      double label study with PHA-L and cholera toxin.
AB  - The inferior colliculus provides a strong descending influence capable of
      modulating the excitability levels of olivocochlear neurons (Rajan, 1990). In an
      attempt to anatomically demonstrate this pathway in rats, an experimental
      paradigm was designed by which anterogradely transported Phaseolus vulgaris
      leucoagglutinin (PHA-L), which delineates axonal arbors, and retrogradely
      transported cholera toxin B subunit alone (CT-B) or conjugated to horseradish
      peroxidase (CT-HRP), which delineate dendritic arbors, are visualized in the same
      brainstem sections. PHA-L was injected unilaterally into the central nucleus of
      the inferior colliculus of adult rats 5-9 days prior to injection of CT-B or CT
      HRP into either the contralateral or the ipsilateral cochlea. Descending
      collicular axons labeled with PHA-L densely innervate the ventral nucleus of the
      trapezoid body (VNTB), which contains neurons of the medial olivocochlear system
      (MOCS), but do not enter the lateral superior olive, where the neurons of the
      lateral olivocochlear system (LOCS) are found. The collicular projection to VNTB
      is largely ipsilateral and supplies mostly the ventral half of the nucleus.
      Within VNTB, the collicular fibers intermingle with dendrites and, to a lesser
      extent, cell bodies of MOCS. Collicular boutons, predominantly of the en passant
      type, are often observed in close apposition to dendrites and, less frequently,
      cell bodies of both crossed and uncrossed MOCS. These light microscopic results
      suggest the existence of direct, synaptic contacts between descending collicular
      axons and ipsilateral crossed and uncrossed MOCS. Numerous collicular boutons
      were also seen at a distance from MOCS, suggesting that they establish synapses
      with other neuron types of the VNTB that do not send their axons to the cochlea.

PMID- 8294263
TI  - Characterization of the outer hair cell's lateral wall membranes.
AB  - We examined the properties of outer hair cell (OHC) lateral wall membranes by
      application of 2 fluorescent membrane probes. The markers, C6-NBD-Ceramide and
      DiOC6, have been used in other cell types to label Golgi apparatus and
      endoplasmic reticulum, respectively. In living isolated OHCs NBD-Ceramide
      demonstrated uninterrupted fluorescence along the OHC lateral wall, while DiOC6
      labeling proved punctate and notably less uniform in this region. In aldehyde
      fixed isolated OHCs both probes exhibited distinct, continuous lateral wall
      fluorescence. Fixed preparations of the organ of Corti labeled with each probe
      demonstrated diffuse fluorescence throughout the inner hair cell cytoplasm unlike
      the uniform, circumferential lateral wall fluorescence seen in OHCs. OHCs exposed
      to salicylate following NBD-Ceramide labeling displayed patchy, less distinct
      labeling along the OHC lateral wall. The thickness of lateral wall fluorescence
      in salicylate exposed cells was 49% greater than control OHCs. We interpreted the
      salicylate induced change in lateral wall labeling as a fluorescent
      representation of previously described ultrastructural dilatation and
      vesiculation of the subsurface cisternae. The distribution of these 2 fluorescent
      probes along OHC lateral wall membranes suggests that the OHC's subsurface
      cisternae are neither Golgi nor ER, but share characteristics of both.

PMID- 8294264
TI  - Mechanism of lack of development of negative endocochlear potential in guinea
      pigs with hair cell loss.
AB  - The endocochlear potential (EP), and the concentration of K+, Na+ and Cl- were
      measured simultaneously in endolymph of guinea pigs. The EP was 85.6 +/- 0.8 mV
      in normal guinea pigs, 90.7 +/- 0.8 mV in the kanamycin-treated animals, and 91.6
      +/- 1.2 mV in those treated with nitrogen mustard-N-oxide (NMNO). Thirty minutes
      after the onset of anoxia, the EP (negative EP) was -29.3 +/- 1.0 mV in the
      normal group, -0.2 +/- 1.0 mV in the kanamycin-treated group, and -1.9 +/- 1.3 mV
      in the NMNO-treated group. The permeability coefficients of K+ (Pk), Na+ (Pna)
      and Cl- (Pcl) across the endolymph-perilymph barrier during the period of 20-30
      min after the onset of anoxia in the normal group were (341.6 +/- 38.2) x 10(-9)
      cm3 sec-1, (53.0 +/- 8.1) x 10(-9) cm3 sec-1 and (111.8 +/- 27.2) x 10(-9) cm3
      sec-1, respectively. Pk was decreased in the kanamycin- and NMNO-treated groups.
      Pna did not differ between the normal and treated groups. Pcl was increased in
      the kanamycin- and NMNO-treated groups. The K+:Na+:Cl- permeability ratio was
      1:0.16:0.32 in the normal group, 1:1.12:11.6 in the kanamycin-treated group, and
      1:0.44:5.60 in the NMNO-treated group. The results indicate that the lack of
      development of a negative EP in the kanamycin- and NMNO-treated guinea pigs was
      attributable to the increased Pcl and the decreased Pk across the endolymph
      perilymph barrier, probably the organ of Corti, during anoxia.

PMID- 8294266
TI  - The effect of sound level, temperature and dehydration on the brainstem auditory
      evoked potential in anuran amphibians.
AB  - Brainstem auditory evoked potentials (BAEPs) were used to examine the effects of
      sound level, temperature, and dehydration on the auditory pathway of three
      species of anuran amphibians: Rana pipiens, Bufo americanus and B. terrestris.
      BAEP latency, amplitude and a measure of threshold were determined for all
      stimulus and test conditions. Threshold values obtained with this technique were
      similar to other neural measures of threshold in anurans, and were stable for
      repeated measures within 12 h and over three days. Transient changes in
      temperature caused non-linear changes in BAEP threshold and latency. Above 20
      degrees C small threshold shifts were elicited, while below 20 degrees C we
      observed rapid deterioration of threshold. Animals acclimated to a cold
      temperature (14 degrees C) were acoustically less sensitive than warm (21 degrees
      C) animals, even when both groups were tested at colder temperatures. Because
      peripheral components of the BAEP were most affected by both transient and
      acclimation (longer term) cooling and warming, the sensory epithelium appears to
      be the most temperature-sensitive component of the auditory pathway. Dehydrated
      frogs showed no auditory dysfunction until a critical level of dehydration was
      reached. More dehydration-resistant species (B. terrestris and B. americanus)
      were less susceptible to BAEP degradation near their critical dehydration level.

PMID- 8294265
TI  - Profound hearing loss in the cat following the single co-administration of
      kanamycin and ethacrynic acid.
AB  - Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA)
      has previously been shown to produce a rapid and profound hearing loss in guinea
      pigs. In the present study we describe a modified technique for developing a
      profound hearing loss in cats. By monitoring the animal's hearing status during
      the intravenous infusion of EA the technique minimizes the effects of individual
      variability to the drug regime. Seven cats received a subcutaneous injection of
      KA (300 mg/kg) followed by intravenous infusion of EA (1 mg/min). Click-evoked
      auditory brainstem responses (ABRs) were recorded to monitor the animal's hearing
      during the infusion. When the ABR thresholds rose rapidly to levels in excess of
      90 dB SPL the infusion of EA was stopped. This occurred at EA doses of 10-25
      mg/kg, indicating considerable individual variability to the deafening procedure.
      However, there was a strong negative correlation (r = -0.93) between the EA dose
      and body weight which accounted for much of this variability. Subsequent ABR
      monitoring showed that this profound hearing loss was both bilateral and
      permanent. Significantly, blood urea and creatinine levels, monitored for periods
      of up to three days after the procedure, remained within the normal range.
      Furthermore, there was no clinical evidence of renal dysfunction as indicated by
      weight loss or oliguria. Cochlear histopathology, examined after a two months to
      three year survival period, showed an absence of all inner and outer hair cells
      in the majority of cochleas. The extent of loss of spiral ganglion cells was
      dependent on their distance from the round window and the period of survival
      following the deafening procedure. Clearly, the degeneration of spiral ganglion
      cells continued for several years following the initial insult. Finally, we
      observed no evidence of renal histopathology. In conclusion, the co
      administration of KA and EA produces a profound hearing loss in cats without
      evidence of renal impairment. Monitoring the animal's hearing status during the
      procedure ensures that the dose of EA can be optimised for individual animals.
      Moreover, it may be possible to adapt this procedure to produce animal models
      with controlled high frequency hearing losses.

PMID- 8294267
TI  - Displacement of the gerbil tympanic membrane under static pressure variations
      measured with a real-time differential moire interferometer.
AB  - It is thought that chronic middle ear disease ultimately causes changes in the
      stiffness and elasticity of the tympanic membrane, but it is unknown whether such
      changes occur early in the course of the disease. In order to analyze mechanical
      changes in different parts of the tympanic membrane, a full field moire
      interferometry technique was utilized to measure the shape and real-time
      displacement in response to positive and negative pressure gradients applied
      across the tympanic membrane. The measurements were performed on fresh isolated
      temporal bones from the Mongolian gerbil. In order to gain sufficient visual
      access to the pars tensa for the moire measurements, the tympanic bulla was
      opened, the tensor tympani muscle and the incudo-stapedial joint were cut, and
      part of the medial wall of the tympanic cavity was removed. The malleus and incus
      and their ligaments were kept intact. The specimens were kept continuously
      humidified with an evaporator or in a humid chamber, since otherwise the tympanic
      membrane dries out in a few minutes when its medial surface is exposed. This
      desiccation reduces the elasticity and cause shrinkage which results in a
      reduction of the height of the cone constituted by the pars tensa. Profiles of
      the tympanic membrane at rest and under different pressure conditions were
      extracted from the moire interferograms. The tympanic membrane and ossicular
      complex exhibit a hysteresis effect as differences in the displacement patterns
      under identical pressure gradients during the loading and the unloading phase; a
      residual displacement of the pars tensa was for instance seen after the pressure
      gradient across the tympanic membrane was eliminated.

PMID- 8294268
TI  - Chronic electrical stimulation reverses deafness-related depression of
      electrically evoked 2-deoxyglucose activity in the guinea pig inferior
      colliculus.
AB  - The [14C]-2-deoxyglucose (2-DG) autoradiographic technique was used to study how
      auditory-related metabolic activity changes with deafness, and how chronic
      electrical stimulation of the deafened system may modify these changes. Guinea
      pigs were deafened by administration of kanamycin and ethacrynic acid. After nine
      weeks of deafness, the basal unstimulated uptake of 2-DG in the inferior
      colliculus (IC) was lower than in normal hearing control animals. 100 microA of
      acute cochlear electrical stimulation significantly increased 2-DG uptake in
      normal hearing animals but did not evoke a significant increase in four or nine
      week deafened animals. Electrically elicited 2-DG uptake in the IC is therefore
      depressed by prolonged deafness. In a second series of experiments, after four
      weeks of deafness, animals were chronically electrically stimulated via a
      cochlear implant 2.5-3.5 h a day, five days a week for five weeks at 100 microA.
      Acute cochlear electrical stimulation following this chronic stimulation
      significantly increased 2-DG uptake in the contralateral IC over unstimulated
      levels. This suggests that some depressive effects of profound deafness on the
      auditory brain stem may be reduced or reversed with chronic electrical
      stimulation by a cochlear implant.

PMID- 8294269
TI  - Influence of floor space allowance and dietary selenium and zinc on growth
      performance, clinical pathology measurements and liver enzymes, and adrenal
      weights of weanling pigs.
AB  - Crossbred weanling pigs (n = 96, average initial weight, 8.4 kg) were used in a 6
      wk trial using a 2 x 2 x 3 factorial arrangement of treatments to determine the
      effects of floor space allowance (.28 and .14 m2/pig), dietary Se (40 and 200
      ppb), and dietary Zn (30, 80, and 250 ppm) on growth performance, clinical
      pathology measurements, serum minerals, and enzymes, liver enzymes, and adrenal
      weights. Pigs (four/pen) were given ad libitum access to feed and water. Body
      weight and feed consumed were recorded weekly, and heparinized blood samples were
      taken for the various assays. Three pigs per pen were killed at the end of the
      trial for gross examination of organs and tissues and for liver enzymes assays.
      Pigs housed with restricted floor space ate 21% less (P < .001) and grew 18% more
      slowly (P < .001) than pigs housed with adequate floor space, but their gain:feed
      ratio was 4% higher (P < .08). Growth performance was not influenced by dietary
      Se and Zn treatments. There was no mortality in any of the treatments, and no
      visible gross abnormalities in organs and tissues at necropsy examination, except
      that more musculoskeletal bruising was observed for pigs housed with adequate
      floor space. This finding is supported by higher serum K concentration and
      creatine phosphokinase activity for pigs housed with adequate floor space.
      Corticosteroid activity and adrenal weights were similar for all treatments.
      Concentrations of blood Se and glutathione peroxidase were positively related to
      dietary Se levels, and serum Zn concentration was related to dietary Zn levels.
      Other effects of dietary Se and Zn on clinical pathology measurements were
      minimal and usually unexplained. Most two-way interactions of Se and Zn with
      floor space allowance were nonsignificant, which suggests that the main effects
      of Se, Zn and floor space were independent. Some hematologic values, serum
      metabolites, serum minerals, and serum and liver enzymes were decreased or
      increased, which is suggestive of stress of pigs housed with restricted floor
      space. However, most values were unchanged, and a few changed in the direction to
      suggest benefits of restricting space; all values were within an expected normal
      range.

PMID- 8294270
TI  - Carcass and meat sensory traits of steers finished on fescue and clover, summer
      forage, or for different periods in drylot.
AB  - During a 3-yr period 184 steers were allotted to five treatment groups. Group 1
      steers were pastured on fescue-clover and slaughtered in the spring at
      approximately 540 d of age. Group 2 steers were pastured on fescue-clover then
      placed on summer pasture regimens and slaughtered at approximately 620 d of age.
      Group 3 steers were treated the same as Group 2 then placed in the drylot for 45
      d. Group 4 steers were treated the same as Group 2 steers then placed in the
      drylot for 75 d. Group 5 steers were placed in drylot after weaning and
      conditioning and were slaughtered at endpoints that corresponded with those for
      Group 3. Steers selected for slaughter at each endpoint were those evaluated to
      have reached the most optimum slaughter weight and finish by project personnel.
      Carcasses of steers from fescue-clover and summer pasture had lower yield grades
      and a lower quality grade than carcasses of steers from drylot (P < .05).
      Carcasses of steers from fescue-clover and summer pasture had a more yellow fat
      covering than carcasses of steers that received a concentrate (Treatments 3, 4,
      and 5, P < .0001). Fescue-clover- and summer pasture-fed steers had a higher
      percentage of lean and a lower percentage of fat in the 9-10-11th rib section
      than did steers that received concentrate (P < .005). Chemical analysis of the
      lean tissue of the 9-10-11th rib section indicated that summer pasture-fed steers
      had a lower percentage of ether extract and higher percentage of moisture than
      the lean tissue from steers that received concentrate (P < .05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8294271
TI  - Production of yearling Targhee or Finn-Dorset-Targhee ewes managed as a farm or
      range flock.
AB  - Production data from 681 yearling ewes were evaluated for the effect of ewe breed
      and management system on fertility, prolificacy, lamb birth weight, lamb
      survival, lamb weaning weight, ewe fleece weight, and total lamb weight weaned
      per ewe exposed. Two hundred seven straightbred Targhee (T) and 474 1/4 Finn-1/4
      Dorset-1/2 Targhee (FDT) crossbred ewes managed in a range or farm flock system
      were included in this study. Ewes were born in 1984 through 1987 and lambed the
      first time as 2-yr-olds. The basic model included main effects of ewe breed and
      management system. Lamb sex was added to the model for birth and weaning weight
      analysis. The FDT ewes had higher (P < .05) fertility (95.3 vs 91.3%) and (P <
      .01) prolificacy (1.93 vs 1.45 lambs) than the T ewes. Targhee ewes had heavier
      (P < .01) lambs at birth (5.2 vs 4.0 kg) and weaning (26.1 vs 23.4 kg, P < .01)
      and produced more (P < .01) wool (3.8 vs 3.2 kg). Lamb survival was not different
      (P > .10) between the breeds or management systems. Although FDT lambs were
      lighter at weaning, FDT ewes weaned 5.8 kg more (P < .01) total lamb weight per
      ewe exposed than did the T ewes (34.7 vs 28.9 kg), because FDT weaned more (P <
      .01) lambs per ewe exposed (1.46 vs 1.09 lambs). Farm flock ewes were more
      prolific (1.73 vs 1.64 lambs, P < .05) and had heavier lamb birth weight (4.8 vs
      4.4 kg, P < .01) than range flock ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294272
TI  - Effect of pasture, confinement, and diet fortification with vitamin E and
      selenium on reproducing gilts and their progeny.
AB  - A total of 48 gilts were used to evaluate the effects of a corn-soybean meal diet
      with or without vitamin E and Se fed on pasture or in confinement. The effects of
      these treatments on gilt serum and tissue alpha-tocopherol and Se concentrations
      and those of their progeny at weaning (28 d) were evaluated. During gestation,
      the experiment was a 2 x 2 factorial arrangement of treatments in a split-plot
      design that compared the housing system (pasture or confinement) and the effect
      of diets fortified with or without vitamin E (22 IU/kg) and Se (.3 ppm). The
      lactation study was a 2 x 2 factorial arrangement of treatments in a split-plot
      design evaluating the two housing systems during gestation or lactation only when
      gilts were fed the unfortified basal diet. The gilts fed the vitamin E- and Se
      supplemented diet remained either on pasture or in confinement during both
      reproductive phases and served as positive controls. Gilts were bled at breeding,
      at 30, 60, and 90 d postcoitum, at farrowing, and at weaning (28 d). Three pigs
      per litter were bled from all litters at weaning. Six pigs per treatment group
      were killed at weaning and livers were collected. Pasture lots contained
      orchardgrass, ryegrass, and alfalfa; different lots were used during each
      reproductive phase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294273
TI  - Forage quality and grazing steer performance from Tifton 85 and Tifton 78
      bermudagrass pastures.
AB  - A new high-yielding bermudagrass hybrid, Tifton 85, produced 26% higher DM yield
      (P = .05) with 11% higher IVDMD (P = .05) than Coastal in two 3-yr yield trials.
      Tifton 78 and Tifton 85 were established in duplicate .81-ha pastures in 1988 and
      were grazed during 1989, 1990, and 1991 using a variable stocking rate method.
      Four tester steers per pasture with 269 kg initial BW grazed continuously for 169
      d/yr beginning in April. Forage mass, targeted at 2,800 kg of DM/ha, was
      maintained by adjusting stocking rates at 14-d intervals to correspond with
      ground-level forage samples taken at 14-d intervals. Pastures received 84 kg of
      N/ha in March, June, and August of each year. Nutritive value was assessed using
      whole masticate samples from two esophageal cannulated steers grazing each
      pasture in late May, mid-July, or early September. The 3-yr mean masticate
      analyses revealed similar CP for Tifton 78 and Tifton 85 in May and July, but
      higher (P < .05) CP for Tifton 85 than for Tifton 78 in September. The IVDMD was
      higher (P < .05) in May and September for Tifton 85 than for Tifton 78; and, mean
      and medium particle sizes were greater (P < .05) for Tifton 85 than for Tifton 78
      in May, July, and September samples.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294274
TI  - Effects of porcine somatotropin on growth and carcass composition of Meishan and
      Yorkshire barrows.
AB  - Effects of porcine somatotropin (pST) on growth and carcass characteristics of
      Meishan (Ms) and Yorkshire (Y) barrows given 3 mg of pST or saline daily were
      determined for two end points. First, 26 Ms and 26 Y barrows were treated from
      119 d of age until the Y barrows reached 108 kg. Second, another 18 Ms barrows
      were treated to 108 kg BW. Age- and weight-matched treatments were analyzed.
      Results for both groups indicated pST effects (P < .05) for feed conversion (+)
      and intake (-), dressing percentage (-), percentage of carcass fat (-) and
      protein and water (+), leaf fat (-), backfat (BF) thickness (-), longissimus
      muscle area (LMA; +), skin thickness (+), muscle firmness and marbling scores (
      ), organ weights (+), belly (-), clear plate (-), ham (+), and total boneless
      cuts (BC; +). Somatotropin effects were also present for loin (-) and boneless
      Boston butt (BBB; +) in the age-matched group and for ADG (+), carcass weight (
      ), loin (-), jowl (-), and tenderloin (+) in the weight-matched group. Breed
      effects (P < .05), in favor of Y barrows, in both treatments existed for ADG (+)
      and feed intake (+), carcass weight (+), dressing percentage (+), LMA (+), skin
      thickness (-), muscle color and firmness scores (-), muscling score (+), all
      wholesale cuts (WC; +) except clear plate (age-matched), all trimmed cuts (TC; +)
      except picnic shoulder (weight-matched), and all BC (+). Breed effects, in favor
      of Y barrows, were also determined for carcass length (+), percentage of carcass
      ash (-), leaf fat (+), average BF thickness (+), and heart (-) and liver (-)
      weights in age-matched animals and percentage of carcass fat (-), protein (+),
      water (+), leaf fat (-), 10th rib, average, and P2 BF thicknesses (-), marbling
      score (-), femur length (-), and liver weights (+) in weight-matched animals. A
      higher response to pST (P < .05) was determined in Ms barrows than in Y barrows
      for percentage of carcass protein (+), liver (+), and heart (+) in the age
      matched treatment and 10th rib BF thickness (-) and heart weight (+) in the
      weight-matched treatment. Yorkshire barrows treated with pST had more improved
      values for color score (+; age-matched) and BBB (+; weight-matched).

PMID- 8294275
TI  - Genetic and statistical properties of residual feed intake.
AB  - Residual feed intake is defined as the difference between actual feed intake and
      that predicted on the basis of requirements for production and maintenance of
      body weight. Formulas were developed to obtain genetic parameters of residual
      feed intake from knowledge of the genetic and phenotypic parameters of the
      component traits. Genetic parameters of residual feed intake were determined for
      a range of heritabilities (h2 = .1, .3, or .5) for component traits of feed
      intake and production, and genetic (rg = .1, .5, or .9) and environmental (re =
      .1, .5, or .9) correlations between them. Resulting heritability of residual feed
      intake ranged from .03 to .84 and the genetic correlation between residual feed
      intake and production ranged from -.90 to .87. Heritability of residual feed
      intake depends considerably on the environmental correlation between feed intake
      and production. Residual feed intake based on phenotypic regression of feed
      intake on production usually contains a genetic component due to production.
      Residual feed intake based on genotypic regression of feed intake on production
      is genetically independent of production and its use is equivalent to use of a
      selection index restricted to hold production constant. Multiple-trait selection
      on residual feed intake, based on either phenotypic or genetic regressions, and
      production is equivalent to multiple-trait selection on feed intake and
      production. Residual energy intake in dairy cattle was examined as an example.
      Heritability of residual energy intake based on genotypic regression was close to
      zero and indicated that measurement of feed intake provides little additional
      genetic information over and above that provided by milk production and body
      weight. The principles outlined in this study have broader application than just
      to residual feed intake and apply to any trait that is defined as a linear
      function of other traits.

PMID- 8294276
TI  - Efficiency of an approximate animal model for maternal and direct genetic effects
      of litter size in swine.
AB  - A simulated population of 120 sows and 24 boars in service per year was used to
      compare genetic evaluations for first-parity litter size and selection response
      when approximate and complete animal models were used. The complete animal model
      included maternal and direct effects. The approximate model did not account for
      covariances between maternal breeding values, or between maternal and direct
      breeding values, but included a random litter effect of birth of sow. After 10 yr
      of selection, the overall response (maternal plus direct) was 2.94, 1.61, and .77
      pigs using the approximate model and 3.11, 1.65, and .67 pigs using the complete
      model with equal weighting of maternal and direct genetic effects in the
      aggregated breeding value for genetic correlations between maternal and direct
      effects of 0, -.5, and -.9, respectively. Higher reduction was obtained in direct
      genetic response that was 5, 8, and 19% lower using the approximate model than
      the complete model for genetic correlations of 0, -.5, and -.9, respectively. Use
      of the approximate model over 10 yr of selection resulted in a bias of estimation
      of direct genetic trend of .24, .54, and .48 pigs and in bias in estimated
      overall response (maternal plus direct) of -.49, .67, and 1.28 pigs for genetic
      correlations between maternal and direct effects of 0, -.5, and -.9,
      respectively. Bias in environmental trend estimated from year-season effects was
      of the same magnitude as the bias in estimated overall response but with an
      opposite sign. With the approximate model, maternal genetic response was due to a
      correlation between maternal genetic effects and direct EBV, which for an
      embedded trait such as maternal genetic effects occurred even when there was no
      correlation between their true genetic effects. Findings suggested that over the
      short term the approximate model can be used without substantial loss of overall
      response but the use of the complete model was recommended because of unbiased
      estimates in genetic and environmental trend and higher direct genetic response.

PMID- 8294277
TI  - Selection for litter size, body weight, and pelt quality in mink (Mustela vison):
      experimental design and direct response of each trait.
AB  - In a five-generation selection experiment, separate lines of mink (Mustela vison)
      were subjected to selection for improved litter size at 3 wk (F line), BW in
      September (BS line), and underfur density (P line), and combined selection for
      litter size and BW (I line). Underfur density was subjectively judged on live
      animals. One unselected line served as a control (C line). Significant changes
      were achieved in each trait: litter size in the last generation was 5.3 in the F
      line vs 3.7 in the C line; September weight in males was 2,254 g in the BS line
      vs 1,979 g in the C line, and the underfur density score, graded using a 5-point
      scale, was 4.1 in the P line vs 2.9 in the C line. In the combined line (I line)
      litter size was only slightly improved, whereas BW was substantially increased
      (male mean = 2,194 g). A univariate animal model was used to predict genetic
      values and to estimate variance components with a REML procedure. Heritability
      estimates were .14 +/- .09 for litter size, .39 +/- .06 for September weight, and
      .21 +/- .06 for underfur density. It was confirmed that the reproductive
      performance of heavy of fat animals was poor. Responses were higher than
      predicted when selecting for September weight and underfur density. In the last
      generation the average breeding values, relative to the base generation, were +.8
      kits for litter size (F line), +365 g for male September weight (BS line), and +1
      point for underfur density (P line). The study suggests that negative maternal
      effects on litter size may exist in mink.

PMID- 8294278
TI  - Genotype x environment interactions in postweaning performance to yearling in
      Angus, Brahman, and reciprocal-cross calves.
AB  - Data from 431 Angus, Brahman, and reciprocal-cross calves were used to evaluate
      performance from weaning to yearling in calves managed during the winter on
      dormant common bermudagrass or endophyte-infected tall fescue (backgrounding
      environments). Calves on bermudagrass were weaned at heavier weights (P < .01)
      but gained less postweaning (P < .01). Weights at 365 d, 365-d hip heights, and
      365-d weight:height ratios were similar between calves on different backgrounding
      environments averaged over breed. There was evidence that heterosis for
      postweaning ADG was larger in calves managed on endophyte-infected tall fescue (P
      < .05), but heterosis estimates for 205-d weight, 365-d weight, 365-d hip height,
      and 365-d weight:height were similar between backgrounding environments. Maternal
      and direct effects did not significantly interact with backgrounding environment,
      but there was a trend for maternal effects of 205-d weight, 365-d weight, and 365
      d weight:height to be larger on the common bermudagrass environment than on the
      tall fescue environment. There was also a trend for direct breed effects for
      postweaning ADG and 365-d hip height to be larger on the common bermudagrass
      environment. These data indicated that genetic effects may vary with production
      environment and that consideration should be given to environment when developing
      crossbreeding systems.

PMID- 8294279
TI  - The behavior of gestating swine housed in the Hurnik-Morris system.
AB  - A group housing system for sows, the Hurnik-Morris (HM) system, was developed to
      address several of the perceived animal welfare limitations of existing housing
      methods. The HM system permits socially coordinated eating and resting,
      controlled and socially undisturbed feed intake, physical exercise, and regular
      exposure to boars. The HM system effectively uses and reinforces the behavioral
      phenomenon of the social synchronization of feeding and provides a less
      restrictive housing environment. The system provides housing for sows in small
      groups and an individual, non-competitive feeding environment using electronic
      feeding compartments. Gilts reared during gestation in the HM system were
      observed to spend less time lying in sternal recumbency (31 vs 21%; P = .004) and
      performing stereotypies (.10 vs .56%; P = .034) and to spend more time
      participating in social activities (1.4 vs .19%; P = .0007) than similar gilts
      kept in gestation crates (GC). The HM sows revealed a significantly longer latent
      period to postprandial lying than did GC gilts (64 vs 32 min; P = .0001). The
      order of gilt entry into the feeding compartments tended to be more consistent
      than the sequence of feeding compartments being entered (W = .57 vs .41; P =
      .06). This indicates that social factors seemed to be more important than spatial
      ones in determining the order of entry into the feeder compartments.

PMID- 8294280
TI  - Thermal requirements of young calves during standing and lying.
AB  - A study of 23, 6-d-old Holstein-Friesian male calves was conducted to evaluate
      the thermal requirements of young calves in relation to their posture (standing
      or lying). Calves were housed individually and were assigned to one of four
      ambient temperatures: 5, 9, 13, or 18 degrees C. Heat production of each calf was
      measured continuously every 9 min by indirect calorimetry for 5 d. The posture
      during these 9-min periods was derived from the continuous measurement of
      physical activity. For both standing and lying, heat production was increased at
      5 and 9 degrees C compared with 13 and 18 degrees C. This increase in heat
      production was larger during standing than during lying. Consequently, the energy
      cost of standing was affected by ambient temperature (173, 189, 144, and 114
      kJ.kg-.75 x d-1 at 5, 9, 13, and 18 degrees C, respectively). The time spent
      standing was not affected by ambient temperature. The thermal requirements of the
      calves were dependent on the posture. Lower critical temperature was 13.5 degrees
      C during lying and 17.0 degrees C during standing. The rate of increase in heat
      production below the lower critical temperature was 7.47 kJ.kg-.75 x d-1 x Co-1
      during lying and 11.24 kJ.kg-.75 x d-1 x Co-1 during standing. These results
      indicate that the increase in heat loss upon standing in the cold is greater than
      the increase in heat production upon standing at thermoneutrality. Consequently,
      young calves require increased cold-induced thermogenesis when they are standing.

PMID- 8294281
TI  - Technical note: quantification of multicatalytic proteinase complex (proteasome)
      activity by ion-exchange chromatography.
AB  - Within 1 h after slaughter, two 10-g samples of longissimus muscle were obtained
      from four crossbred beef cattle. Samples were homogenized in three or six volumes
      of extraction solution that consisted of 50 mM Tris base, 10 mM EDTA, and 10 mM 2
      mercaptoethanol, pH adjusted to 8.3 with 6 N HCl. After centrifugation the
      supernatant from the three-volume extract was fractionated by addition of solid
      (NH4) 2SO4. Proteins that precipitate between 40 and 65% (NH4) 2SO4 were dialyzed
      and then loaded onto a DEAE-Sephacel column and eluted with a continuous gradient
      of NaCl from 100 to 400 mM (125 mL of each; Method A). The six-volume extract was
      loaded onto a DEAE-Sephacel column and eluted with a continuous gradient of NaCl
      from 0 to 350 mM (250 mL of each; Method B). Total peptidase activity eluted from
      the column was determined using the synthetic peptide N-CBZ-Gly-Gly-Leu-p
      nitroanilide. Method B yielded greater multicatalytic proteinase complex (MCP)
      activities (picomoles of p-nitroaniline released/hour-1) per gram of muscle
      (1,538.25 +/- 105.15) than did Method A (1,195.05 +/- 86.55; P < .05). In
      addition, Method B permitted the quantification of calpain activity from the same
      fractions eluted. The relationship between enzyme activity and assay time (up to
      45 min) and protein concentration (up to 10 micrograms) in the assay was linear.
      Studies indicated that the optimum temperature is in the range of 50 to 60
      degrees C and the optimum pH in the range of 7.5 to 8.5.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8294282
TI  - Performance, clinical chemistry, and carcass responses of finishing lambs to
      recombinant bovine somatotropin and bovine placental lactogen.
AB  - Bovine placental lactogen (PL) is a partial somatotropin agonist in the cow and
      decreases urea nitrogen, indicating increased nitrogen retention. In the present
      study, the somatogenic effects of bovine PL (bPL; 4 and 8 mg/d) were compared
      with those of bovine somatotropin (bST; 4 and 8 mg/d) in finishing lambs.
      Measures of comparison included growth performance, carcass composition, and
      growth-related clinical chemistry traits. Although feed efficiency during the
      first 3 wk of treatment with bPL was improved by 14% (P < .05), feed efficiency
      for the full 6-wk treatment period did not differ from that of control lambs.
      Responsiveness to bPL may have been attenuated by high titer antibodies present
      after 2 wk of treatment. However, bPL also did not influence growth-related
      clinical chemistry traits during short-term (7 d) treatment, strongly suggesting
      that bPL was ineffective in finishing lambs at the doses tested. In contrast, bST
      improved 6-wk feed efficiency by an average of 17% (P < .05) and decreased feed
      intake by an average of 12% (P < .05). In addition, measures of carcass
      composition including longissimus muscle area, specific gravity of the rack,
      kidney and pelvic fat, and fat thickness demonstrated that bST, but not bPL,
      treatment decreased carcass fatness and increased carcass leanness. Treatment
      with bST, but not with bPL, affected IGF-I, insulin, glucose, and urea nitrogen
      in a dose-related manner. Thus, daily injections of bPL did not affect either
      performance or carcass quality, whereas performance and carcass responses of
      finishing lambs to bST were consistent with those reported by others.

PMID- 8294283
TI  - Skeletal muscle growth and expression of skeletal muscle alpha-actin mRNA and
      insulin-like growth factor I mRNA in pigs during feeding and withdrawal of
      ractopamine.
AB  - Sixty crossbred barrows were used to study the effect of ractopamine (a
      phenethanolamine/beta-adrenergic agonist) treatment and its withdrawal on muscle
      growth and on the relative abundance of skeletal muscle alpha-actin (sk-alpha
      actin) mRNA and of liver and longissimus muscle IGF-I mRNA at 4 wk. Ractopamine
      was fed (20 ppm) for periods of 2, 4, and 6 wk (six pigs per group). Additional
      pigs (four per group) were fed ractopamine (20 ppm) for 6 wk and then slaughtered
      1, 3, and 7 d after withdrawal of ractopamine. Ractopamine increased (P < .05)
      longisimus muscle weight and protein content, although protein concentrations
      were not different. The increased muscle weight and protein content attained by
      feeding ractopamine for 6 wk was retained when ractopamine was withdrawn. The RNA
      and DNA concentrations did not change, whereas total DNA and RNA content per
      muscle was 18 and 26.7% greater, respectively, in ractopamine-treated pigs at 4
      wk, but there were no differences at 2 or 6 wk or among the withdrawal groups.
      The relative abundance of sk-alpha-actin mRNA in the longissimus muscle was 41
      and 62% greater (P < .05) in treated animals at 2 and 4 wk but was similar to
      that in controls at 6 wk and during the withdrawal period. The relative abundance
      of IGF-I mRNA in liver and longissimus muscle was not altered with ractopamine
      treatment for 4 wk. These results indicate that the ractopamine-enhanced muscle
      growth may result from increased myofibrillar gene expression at the
      pretranslational level, which is maximal with short-term treatment of
      ractopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294284
TI  - Plasma growth hormone, insulin-like growth factor, insulin, and thyroid hormone
      association with body protein and fat accretion in steers undergoing compensatory
      gain after dietary energy restriction.
AB  - Eighteen Chianina crossbred steers were used to examine the interrelationship
      between hormonal status and empty body protein (EBPRT) and fat (EBFAT) accretion
      during an 88-d controlled realimentation (REAL; DMI was adjusted weekly on an
      individual BW basis) period. Body composition was determined by monitoring
      endogenous whole-body 40[K]. At the end of restriction (REST) and on d 31 and 59
      of REAL blood samples were taken and analyzed for concentrations of growth
      hormone (GH), IGF-I, IGF-II, insulin (INS), thyroxine (T4), triiodothyronine
      (T3), reverse triiodothyronine (rT3), nonesterified fatty acids (NEFA), glucose,
      and urea nitrogen. Depositions of EBPRT and EBFAT were decreased (P < .001) in
      REST (92 d) animals compared with nonrestricted (NR) controls. During REST,
      plasma levels of glucose, IGF-I, INS, T4, T3, and rT3 were decreased (P < .05);
      plasma urea nitrogen (PUN), NEFA, and GH levels were increased (P < .05), and IGF
      II concentrations were similar between REST and NR steers. A transient
      compensatory response in BW gain and protein deposition occurred in repleted
      steers between d 35 and 62 of REAL. During this period, PUN levels markedly
      declined (P < .01) in REAL steers and glucose concentration increased (P < .01)
      to levels similar to those in NR controls. This response prevailed even though
      apparent digestible nutrients were decreased in repleted animals. During energy
      repletion, plasma levels of T4, T3, rT3, IGF-I, and INS were positively, and of
      GH was negatively, correlated with EBPRT and EBFAT gain in repleted animals.
      Unlike IGF-I, IGF-II was not correlated with compensatory body growth. These
      results suggest that compensating steers are more metabolically efficient; rapid
      body tissue gain occurs during a period of reduced nutrient digestibility.
      Additionally, plasma levels of IGF-I, GH, INS, and thyroid hormones, but not of
      IGF-II, are markedly affected by alteration of energy intake and are highly
      correlated with empty body gain and protein deposition in compensating late
      maturing steers.

PMID- 8294285
TI  - Muscle cellularity and postnatal growth in the pig.
AB  - Fast-growing strains of pigs and of other animals tend to have more muscle fibers
      than do slow-growing strains. The relationship between fiber number and growth
      rate was extended by examining pigs within the same strain. Seven litters of pigs
      (n = 66) were weighted at monthly intervals from birth to approximately 80 kg.
      The semitendinosus muscle was removed and an estimation of total fiber number,
      total primary fiber number, and mean secondary:primary fiber number (S:P) ratio
      was made for each animal. Pig growth was divided into three approximately linear
      phases: birth to 6 kg, 6 to 25 kg, and 25 kg to slaughter weight. Average daily
      gain in the first two phases was correlated with birth weight (r = .3614, P < .05
      and r = .5873, P < .001, respectively) but was not correlated with total muscle
      fiber number. In the third growth phase ADG was correlated with muscle fiber
      number (r = .4149, P < .001) and was not correlated with birth weight. The
      gain:feed ratio was also calculated for each pig during the third growth phase
      and was found to be correlated with fiber number (r = .4191, P < .001). These
      results suggest that muscle fiber number is an important determinant of postnatal
      growth such that pig littermates with a high fiber number tend to grow faster and
      more efficiently than littermates with a lower fiber number.

PMID- 8294286
TI  - Carcass and muscle characteristics of Yorkshire, Meishan, Yorkshire x Meishan,
      Meishan x Yorkshire, Fengjing x Yorkshire, and Minzhu x Yorkshire pigs.
AB  - Five barrows and five gilts from each of the following breed types, Yorkshire
      (Y), Meishan (Ms), Fengjing x Y, Minzhu x Y, Ms x Y, and Y x Ms were slaughtered
      at an average live weight of 103 kg. Carcass composition and muscle
      characteristics were evaluated at 24 h postmortem. Chemical characteristics and
      palatability attributes were evaluated on the longissimus and semimembranosus
      muscles. No significant interactions between breed x muscle, breed x sex, or
      muscle x sex were observed so data were pooled across muscle and sex. Yorkshire
      had higher (P < .05) carcass weight, longissimus muscle area, trimmed and
      boneless ham and loin weights, and boneless picnic weight than Ms and the
      crossbreds were intermediate between Y and Ms. Yorkshire had higher (P < .05)
      muscling score, untrimmed ham weight, trimmed picnic weight, and juiciness score.
      Yorkshire had a lower cholesterol content than Ms or crossbreds, and Y had the
      highest water-holding capacity. The longissimus muscle from Ms and the crossbreds
      was firmer than that from Y (P < .05), and muscle from Ms had a higher pigment
      concentration (P < .05). Yorkshire and Fengjing x Y had higher tenderness scores
      (P < .05).

PMID- 8294287
TI  - Effects of diet and hindgut defaunation on diet digestibility and microbial
      concentrations in the cecum and colon of the horse.
AB  - The effects of diet and hindgut defaunation (removal of protozoa from the
      hindgut) on diet digestibility (Trial 1) and on total and cellulolytic bacterial
      and fungal concentrations in the cecum and colon (Trial 2) were investigated. A
      high-forage (HF) diet, 90% alfalfa hay-10% concentrate, or a higher-concentrate
      (HC) diet, 60% alfalfa hay-40% concentrate, was limit-fed. In Trial 1,
      defaunation resulted in a slight decrease in DM digestibility (P < .1) and had no
      effect on cellulose digestibility. Dry matter digestibility was higher (P < .001)
      with the HC diet; however, no differences were observed in cellulose digestion.
      For the faunated periods, protozoal concentrations were similar in the cecum and
      greater in the colon for both diets (P < .05). A diet x location interaction was
      observed for the genera Buetschlia and Blepharocorys. In Trial 2, defaunation had
      no effect on either total or cellulolytic bacterial concentrations in the cecum
      or colon. Total bacterial concentrations were higher (P < .06) in the colon when
      ponies were fed the HC diet. Defaunation did not affect total fungal
      concentrations in the cecum; however, fungal concentrations in the colon were
      slightly higher (P < .1) when the ponies were defaunated. Diet had no effect on
      total or cellulolytic fungal concentrations. Both total and cellulolytic fungal
      concentrations were approximately 10-fold higher in the colon than in the cecum
      (P < .01). Protozoa do not seem to play an essential role in the fermentation of
      feedstuffs in the equine hindgut.

PMID- 8294288
TI  - Supplementing corn-soybean meal diets with microbial phytase linearly improves
      phytate phosphorus utilization by weanling pigs.
AB  - Two experiments were conducted with weanling pigs to determine the effectiveness
      of a dietary supplement of Aspergillus niger phytase in improving the
      availability of phytate-P in corn-soybean meal diets without supplemental
      inorganic P. Experiment 1 consisted of two P and Ca balance trials and two
      feeding trials. Twelve pigs (8.18 +/- .44 kg BW) were housed individually in
      stainless steel metabolism cages. Six pigs received 750 phytase units (PU)/g of
      basal diet and the other six pigs received the basal diet without supplemental
      phytase as control. In Exp. 2, 96 pigs (8.81 +/- .75 kg BW) were allotted to 16
      partially slotted floor pens and their basal diets were supplemented with either
      0, 250, 500, or 750 PU/g for 4 wk. Individual pig weights and pen feed
      consumption were measured weekly. Blood samples were taken from all pigs at the
      end of each trial in Exp. 1 and from three pigs per pen weekly in Exp. 2 to
      measure serum (plasma) inorganic P (P) and Ca concentrations and alkaline
      phosphatase (AP) activities. The results of Exp. 1 indicated that dietary phytase
      increased P retention by 50% (P < .0001) and decreased fecal P excretion by 42%
      (P < .0001). Pigs that received dietary phytase had serum P and Ca concentrations
      and serum AP activities that were nearly normal, whereas control pigs had values
      indicative of a moderate P deficiency. Favorable effects of phytase disappeared
      when the phytase was removed from the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294289
TI  - Supplementing corn-soybean meal diets with microbial phytase maximizes phytate
      phosphorus utilization by weanling pigs.
AB  - Two experiments were conducted with crossbred weanling pigs to determine the
      optimal dietary supplement of Aspergillus niger phytase activity to a low-P, corn
      soybean meal basal diet (BD). In Exp. 1, 50 pigs (7.61 +/- .56 kg BW) received
      the BD supplemented with 750, 1,050, 1,250, or 1,350 phytase units (PU)/g, or
      .21% P as mono-dibasic calcium phosphate (MDCaP) for 4 wk. In Exp. 2, 12 pigs
      (6.39 +/- .74 kg BW) were individually housed in metabolism cages and received
      BD, BD plus the optimal phytase activity (1,200 PU/g), or BD plus .21% P as MDCaP
      for 2 wk. In Exp. 1, additions of phytase > 1,050 PU/g of BD did not improve ADG,
      ADFI, gain/feed, or plasma AP activity. Quadratic relationships between dietary
      phytase activity and these measures were found and their stationary points were
      at approximately 1,200 PU/g of BD. Estimated maximum responses of these measures
      in pigs fed phytase were > or = 90% compared with MDCaP. Pigs fed 1,250 PU/g of
      BD maintained normal plasma P and Ca concentrations. In Exp. 2, pigs that
      received 1,200 PU/g of BD utilized dietary P more effectively (P < .05) than pigs
      fed the BD or the BD plus MDCaP. Although they consumed 44% less P per day, these
      pigs retained only 7% less P than pigs that received MDCaP. One thousand units of
      phytase activity supported retention of 1.1 mg of P from the BD, and this level
      of phytase supplementation was equivalent in effect to .91 mg of P from
      MDCaP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294290
TI  - Evaluation of feed grains with dried skim milk and added carbohydrate sources on
      weanling pig performance.
AB  - Two experiments were conducted to evaluate the effects of 1) two grain mixtures
      and 2) various carbohydrate sources and levels fed to weanling pigs during the
      initial 2 wk postweaning. A total of 720 crossbred pigs were weaned at 23 +/- 2 d
      of age at an average BW of 5.8 kg. In Exp. 1, a 2 x 3 factorial experiment in a
      randomized complete block design was conducted in 12 replicates. Treatment diets
      formulated to 1.40% lysine were fed for a 14-d period. These diets contained
      dried skim milk (DSM) at a 45% level and an oat groat-soybean meal (OG-SBM-DSM)
      or a corn-soybean meal (C-SBM-DSM) mixture. In addition, the diets contained one
      of three carbohydrate sources (cornstarch, dextrose, lactose) at a 12% level.
      From 15 to 35 d postweaning, all groups were fed a 1.15% lysine corn-soybean meal
      (C-SBM) diet. The results demonstrated that during the period from 0 to 14 d
      weight gains were similar when either grain source was provided, but gain:feed
      ratio was superior and serum urea N was lower when the OG-SBM-DSM diet was fed.
      The addition of lactose or dextrose to either grain mixture resulted in greater
      weight gains (P <.05) than when cornstarch was the carbohydrate source. The
      second experiment was a randomized complete block design conducted in six
      replicates. The C-SBM-DSM diet of Exp. 1 served as the positive control diet. The
      other diets used corn gluten meal (CGM), SBM, and DSM with the three carbohydrate
      sources added at 22.5 or 35.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294291
TI  - Effect of niacin additions to corn-soybean meal diets on performance of pigs from
      weaning to finishing.
AB  - An experiment was conducted to study the effect of adding crystalline niacin to
      low-protein diets on pig performance from weaning to market weight. Niacin was
      added at 0, 3, 9, 27, or 81 ppm to a low-protein test (LPT) diet fortified with
      crystalline amino acids and at 0 or 81 ppm to a positive control (PC) diet. Pens
      (four pigs/pen) were the experimental units with 12 and 8 pens per treatment
      during the 35-d nursery and 98-d growing-finishing phases, respectively. Niacin
      supplementation did not affect (P > .10) ADFI, ADG, gain:feed ratio, hair and
      skin condition, or the incidence of toe cracks and lameness during the nursery or
      the growing-finishing phases. There were no linear, quadratic, or cubic responses
      (P > .20) with increasing concentrations of added niacin in the LPT diets for the
      production criteria measured. Also, there were no interactions (P > .20) between
      niacin (0 or 81 ppm) and protein level (LPT or PC diets) for any of the criteria
      studied. Pigs fed the PC diets had greater (P < .05) ADFI, ADG, and gain:feed
      ratios over the entire experiment than pigs fed the LPT diets that contained 0 or
      81 ppm of added niacin. In conclusion, the addition of niacin to low-protein or
      positive control corn-soybean meal diets did not improve pig performance criteria
      from weaning to market weight.

PMID- 8294292
TI  - Prediction of digestibility of nutrients and energy values of pig diets from
      chemical analysis.
AB  - The DE and ME values and digestible nutrient contents of 114 diets were measured
      in 45-kg growing pigs (four to five animals per diet) fed approximately 500 kcal
      of ME/kg BW.60. Diets differed widely with regard to their chemical
      characteristics and their ingredients. Chemical composition of each diet was
      measured by at least four laboratories. The results were used to establish
      prediction equations of DE or ME values, digestible nutrient contents, and
      digestibility coefficients of energy and nutrients from chemical characteristics.
      Digestibility coefficients of energy (range: 65 to 95%) and CP (range: 64 to 94%)
      were highly dependent on dietary fiber and mineral contents. The digestibility
      coefficient of ether extract increased curvilinearly (from 2 to 84%) with the
      dietary fat content. The digestibility of fiber was lower (45% for NDF) than for
      the other chemical constituents. The ME:DE ratio averaged 96.3% and was
      negatively correlated to the dietary protein content. The DE and ME values could
      be accurately predicted (R2 > .90 and CV < 2%) from chemical characteristics; the
      best equations were obtained when the following predictors were combined in a
      linear model: ash, ether extract, crude protein, and an estimate of dietary
      fiber. The accuracy of the prediction was higher with NDF than with ADF or Weende
      crude fiber. The results suggest that even a rather large proportion of dietary
      fiber (approximately 50%) is degraded in the digestive tract, the amount of
      available energy from fiber digestion is negligible in connection with increased
      endogenous protein and fat losses. The equations obtained in the present study
      represent a basis for the prediction of the energy values of mixed diets with a
      composition of unknown ingredients.

PMID- 8294293
TI  - The effect of added dietary soybean oil on vitamin E status of the horse.
AB  - Fourteen 2-yr-old Quarter Horses and Quarter Horse x Thoroughbreds were randomly
      assigned to either a control (CTRL) diet or a diet supplemented with 6.4% soybean
      oil (SBO). The amounts of both diets that were fed met current NRC nutrient
      requirements and were isoenergetic with similar nutrient:energy ratios. Venous
      blood samples (20 mL) were taken at d 0, 30, 60, and 90 of the experiment and
      analyzed for serum alpha-tocopherol, serum cholesterol, and serum triglyceride.
      The sum of serum cholesterol and serum triglyceride values was used as an
      estimate of serum total lipid. The ratio of serum alpha-tocopherol:serum total
      lipid was used as a measure of vitamin E status of horses. The SBO group had
      higher serum cholesterol concentrations (P < .001) at 30, 60, and 90 d. Serum
      triglyceride was not affected by diet. Serum total lipids tended to be greater (P
      < .06) for the SBO group. Serum alpha-tocopherol was greater (P < .001) at 90 d
      in the SBO group. There was a significant correlation (P < .001, r = .62) between
      serum total lipids and serum alpha-tocopherol concentrations in the SBO group.
      This correlation was not significant (P < .07, r = .35) in the CTRL group. The
      ratio of serum alpha-tocopherol:serum total lipid was not affected by diet. The
      results of this experiment suggest that vitamin E status in non-exercising, 2-yr
      old horses fed currently recommended levels of vitamin E was not affected by the
      addition of 6.4% SBO to the diet.

PMID- 8294294
TI  - Transfer of split goat embryos without zonae pellucidae either fresh or after
      freezing.
AB  - Embryos in the morula to blastocyst stage were collected from superovulated goats
      either surgically or after slaughter. Embryos with good or fair morphology were
      bisected with a microblade without the aid of a holding pipette or other
      microinstruments. Of 103 morulae and 77 blastocysts that were split, 200 (97%)
      and 151 (98%) demi-embryos, respectively, with no major morphological aberrations
      were obtained. Zona-free demi-embryos derived from blastocysts were incubated in
      vitro for 2 h, and those derived from morulae for 24 h so that they would reach
      the blastocyst stage. Demi-embryos were transferred either fresh or after
      freezing and thawing. After 2 h of incubation, a significantly higher proportion
      of zona-free demi-embryos derived from blastocysts were of good quality than were
      zona-free demi- embryos derived from morulae (75 vs 45%). Seventy-six percent of
      zona-free demi-embryos derived from morulae developed to the blastocyst stage
      after 24 h in vitro. The quality of the embryos before splitting had a
      significant effect on the development of the demi-embryos in vitro. Transfer of
      11 pairs of zona-free demi-embryos resulted in the birth of five twin and three
      singleton kids. Transfer of 11 pairs of demi-embryos frozen-thawed without zonae
      pellucidae resulted in the delivery of two singleton kids.

PMID- 8294295
TI  - Expression of a bovine growth hormone transgene inhibits pregnant mare's serum
      gonadotropin-induced follicle maturation in prepuberal gilts.
AB  - Prepuberal gilts were injected with PMSG to determine whether expression of a
      bovine growth hormone (bGH) transgene inhibited preovulatory maturation of
      ovarian follicles. Seven transgenic (TG) gilts of line 3706, which expresses a
      mouse metallothionein-bGH transgene, and eight nontransgenic, control (C) gilts
      (128 to 147 d old) were injected with PMSG, 12.5 IU/kg BW, 72 h before necropsy.
      Surface ovarian follicles > or = 1 mm in diameter were counted, measured for
      diameter, and aspirated for fluid. Follicles were classified morphologically as
      healthy or atretic and those with follicular fluid estradiol-17 beta > or = 100
      ng/mL were classified as estrogenactive (EA). The number of follicles per gilt
      was 64.3 +/- 6.1 (mean +/- SEM) and did not differ significantly between bGH-TG
      and C gilts. The PMSG treatment induced growth of large (> 5 mm) follicles in
      both bGH-TG and C gilts. However, compared with C gilts, bGH-TG gilts had fewer
      (P < .05) large follicles (5.9 +/- 1.5 vs 18.3 +/- 5.4), a lower proportion of EA
      large follicles (35 +/- 12.5 vs 69 +/- 13.2%), and in large follicles less (P <
      .05) estradiol-17 beta (86 +/- 17 vs 350 +/- 69 ng/mL) and androstenedione (300
      +/- 33 vs 1,283 +/- 221 ng/mL). Follicular fluid progesterone and inhibin did not
      differ significantly between bGH-TG and C gilts. The incidence of atresia among
      small and medium follicles did not differ significantly between bGH-TG and C
      gilts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294296
TI  - Effects of zinc-treated soybean meal on ruminal fermentation and intestinal amino
      acid flows in steers fed corn silage-based diets.
AB  - The objectives of this study were to examine the effects of feeding zinc-treated
      soybean meal (Zn-SBM) on ruminal fermentation patterns and duodenal AA flows in
      steers fed diets based on corn silage and corn. Six steers (385 kg) fitted with
      ruminal, duodenal, and ileal cannulas were used in a replicated 3 x 3 Latin
      square design experiment with 14-d periods. Diets were supplemented with solvent
      extracted soybean meal (SBM), Zn-SBM, or a 50:50 combination (CP basis) of SBM:Zn
      SBM. Ruminal escape N content of SBM and Zn-SBM were 30.0 and 57.0%,
      respectively, based on 12-h Dacron bag incubation. Protein sources provided
      approximately 30% of total CP in diets containing 12.6% CP (DM basis). Dry matter
      intake was equalized throughout the study at 2.2% of average initial BW. Total N
      flow at the duodenum was similar (P = .47) among treatments, but a trend (P =
      .15) for increased nonmicrobial N flow occurred when SBM and Zn-SBM were fed in
      combination. Micobial N flow and true efficiency of microbial CP synthesis were
      not affected by treatment (P = .87 and .37, respectively). Ruminal fermentation
      characteristics generally were unaffected (P > .10) by protein source. A positive
      quadratic response (P < .06) was observed for total and essential AA flows to the
      small intestine because flows of total and essential AA from ruminally undegraded
      dietary protein tended (P = .12) to increase when SBM and Zn-SBM were fed in
      combination. Absorption of AA from the small intestine also showed a positive
      quadratic (P < .06) response for SBM:Zn-SBM. Microbial AA flow to the small
      intestine was similar (P = .87) among treatments.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8294297
TI  - Forage intake and digestion by cattle grazing midgrass prairie rangeland or
      sideoats grama/sweetclover pasture.
AB  - In mid-May, beef cattle fitted with esophageal (four steers/pasture) or ruminal
      and duodenal cannulas (six heifers/pasture; 274 +/- 6 kg BW +/- SE) grazed
      midgrass prairie (excellent range condition; PRAIRIE) or a seeded mixture of
      sideoats grama (48% of pasture DM) and sweetclover (6% of pasture DM; Bouteloua
      curtipendula [Michx.] Torr./Melilotus officinalis [L.] Lam.; PASTURE). Masticate
      NDF, ADF, and in vitro OM disappearance did not differ (P > .11) between forage
      types (average = 66.6, 36.1, and 58.8% of OM). Only N differed (P = .02) between
      PRAIRIE (2.1) and PASTURE (2.4% of OM). Extents of in situ OM and N disappearance
      were greater (P < .05) and rate of N disappearance between 12 and 36 h was slower
      (P < .10) from PRAIRIE than from PASTURE masticate. Based on in situ data, the
      ruminally degraded N: ruminally degraded OM (grams/kilogram) ratio differed (P <
      .05) between PRAIRIE (22) and PASTURE (25). Ruminal ammonia N concentration
      (milligrams/deciliter) was less (P = .02) for PRAIRIE (2.8) than for PASTURE
      (3.8). Forage OM intake and fecal OM output did not differ (P > .72; average =
      8,207 and 3,380 g/d), but duodenal OM flow tended (P = .13) to be greater
      (PRAIRIE = 4,892, PASTURE = 5,170 g/d) in cattle grazing PASTURE. Apparent and
      true ruminal OM digestion did not differ between forage types (P > .18; average =
      38.3 and 48.5%). Nitrogen intake, nonammonia N, and forage N flow at the duodenum
      were greater (P < .04) for PASTURE (198 vs 171, 242 vs 210, and 162 vs 135 g/d)
      than for PRAIRIE. Microbial N flow (average = 78 g/d) and microbial efficiency
      (average = 20 g of microbial N/kg of OM truly fermented) did not differ (P > .25)
      between forage types. Apparent and true ruminal N digestion did not differ (P >
      .65; average = -26.6 and 19.3%) between forage types. Flow of nonammonia N was in
      excess relative to digestible OM intake; hence, digestible OM intake seemed to be
      first-limiting for performance by cattle grazing either forage type.

PMID- 8294298
TI  - Vitamin E is not degraded by ruminal microorganisms: assessment with ruminal
      contents from a steer fed a high-concentrate diet.
AB  - Using an in vitro incubation system containing undiluted ruminal contents from a
      steer fed a high-concentrate, corn-based diet, we examined microbial degradation
      of DL-alpha-tocopherol acetate (TA). Gas production, pH, and fermentation acid
      profiles were done in an initial experiment to ensure conditions for
      reproducible, viable cultures over 24 h. The pH decreased from 5.7 to 4.9, gas
      production averaged 3.4 mL/mL of ruminal contents, and > 300 mM fermentation
      acids were produced. We then monitored the fate of TA added to bottles containing
      ruminal contents. Three methods of TA extraction were tried, of which two were
      used in experiments. The two methods used were 1) hot ethanol in a Soxhlet
      apparatus and 2) chloroform/methanol. Each of these was used to extract added TA
      from a set of three in vitro experiments. Concentrations of TA were determined at
      0 h and after 4, 8, and 24 h at 39 degrees C. In the three hot ethanol extracted
      experiments, TA recoveries were 85% at 0 h. With time of incubation, TA levels
      either 1) remained constant, 2) decreased then returned to the initial value, or
      3) decreased by approximately 50%. These inconsistent results indicated that this
      extraction method was unacceptable. In the latter three experiments we used a
      chloroform/methanol extraction method. Recoveries of added TA averaged 96%
      overall. Thus, the level of TA remained constant during the 24-h period,
      suggesting that microbial destruction of TA does not occur. Rather, the
      previously reported losses of vitamin E may be attributable to incomplete
      extraction of tocopherol from high-concentrate ruminal contents.

PMID- 8294299
TI  - Cane molasses and cottonseed meal supplementation of ammoniated tropical grass
      hay for yearling cattle.
AB  - Laboratory, digestion, and growth studies were used to evaluate liquid cane
      molasses (MOL) and(or) cottonseed meal (CSM) supplementation of ammoniated (4% of
      the forage DM) stargrass (Cynodon nlemfuensis Vanderyst var. nlemfuensis) hay.
      Ammoniation increased (P < .01) total N concentration (1.0 to 1.4% vs 1.7 to
      2.8%) and in vitro digestion of OM, NDF, and ADF and decreased (P < .01) NDF
      concentration of stargrass hay. Two digestion (4 x 4 Latin square, 250-kg steers)
      and two growth (230-kg Brahman crossbred steers, seven to eight steers per
      pasture, three to four pastures per treatment, October through February) trials
      evaluated MOL and(or) CSM supplementation of ammoniated hay. Supplementation with
      CSM alone did not influence (P > .05) apparent digestibilities of OM or NDF,
      whereas supplementation with MOL either alone or with CSM increased (P < .05)
      apparent OM digestibility, but decreased (P < .05) apparent NDF digestibility. In
      the growth trials, hay intake was not affected (P > .05) by supplementation with
      CSM alone and was decreased (P < .05) by supplementation with MOL either alone or
      with CSM; however, total feed intake was increased (P < .05) by MOL
      supplementation. Cattle fed only ammoniated hay gained approximately .20 kg/d. In
      both trials, daily gain and gain/feed were improved (P < .05) by CSM (.39 to .47
      kg; .062 to .071) or MOL (.34 to .35 kg; .047 to .048) supplementation.
      Improvements (P < .05) in daily gain (.54 to .76 kg) and gain/feed (.077 to .083)
      by supplementation with MOL plus CSM were additive to responses from
      supplementation with MOL or CSM individually.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294300
TI  - Combined effects of stocking rate and supplemental feeding level on adult beef
      cows grazing native rangeland in Texas.
AB  - A grazing study was conducted over 4 yr to determine the effects of stocking rate
      and supplemental feeding levels on intake, and BW and body condition changes by
      adult beef cows. Stocking rates were 12.3, 16.5, and 24.7 animal units/(100
      ha.yr). Supplemental feed treatments included a negative control (NC) and 300
      g/(cow.d) of CP with either 2 (L), 4 (M), or 8 (H) Mcal/(cow.d) of DE from early
      December to late March. Groups fed supplements (L, M, and H) lost less BW from
      fall to spring (P < .01) and reciprocally gained less BW from spring to weaning
      (P < .01) than NC cows. The L cows tended (P = .14) to lose less BW between fall
      and spring than M and H cows. Treatment effects on condition score were similar
      to those for BW change. Forage intake, estimated by measurements of fecal output,
      was greater by supplemented cows (P = .02); L was greater than M and H (P =
      .004). Increased stocking rate correlated with increased fall-to-spring BW losses
      (P < .002), spring-to-weaning BW gains (P < .0001), and decreased winter forage
      intake (P < .005). These data provide quantitative bases for the effects of
      stocking rate and supplemental feeding on BW and condition dynamics. Low-level
      feeding of a high-protein supplement can increase intake of dormant range forage,
      thereby increasing nutrient intake. High-level feeding of low-protein supplements
      seems to increase nutrient status primarily by providing supplemental nutrients.
      Increasing stocking rate to the reported extremes decreased forage intake and
      resulted in unfavorable BW and condition changes.

PMID- 8294301
TI  - Technical note: an algebraic method for calculating fecal output from a pulse
      dose of an external marker.
AB  - Fecal output estimates derived from a one-compartment, Gamma-2, age-dependent
      model were compared with estimates derived algebraically by computing the area
      under the marker excretion curve for lambs given a pulse dose of ytterbium
      labeled forage. Lambs were fed one of four diets (as-fed basis): 100% alfalfa
      hay, 100% prairie hay, 50:50 alfalfa:sorghum grain, and 50:50 prairie hay:sorghum
      grain. For the one-compartment model, fecal output was calculated as the dose of
      Yb (micrograms) divided by the initial concentration in the compartment
      (micrograms of Yb/gram of DM) multiplied by the age-dependent rate constant
      (hours-1). For the algebraic method, fecal output was calculated as the dose of
      Yb divided by the area under the marker excretion curve ([micrograms of Yb/gram
      of fecal DM].hours), both with the full complement of fecal samples and with
      fecal samples collected at 12-h intervals. Fecal output estimated by the three
      methods did not differ (P > .15) from measured fecal output (total collection).
      Marker retention time calculated from the one-compartment, age-dependent model
      was numerically greater (P > .10) than retention time calculated algebraically
      (sum of concentration x time divided by sum of concentrations weighted for
      collection interval) for lambs fed all four diets. These results suggest that the
      area under the marker excretion curve generated from a pulse dose of Yb-labeled
      forage will provide estimates of fecal output that do not differ from those
      calculated from a one-compartment, age-dependent model.

PMID- 8294302
TI  - The effect of monensin supplementation on ruminal ammonia accumulation in vivo
      and the numbers of amino acid-fermenting bacteria.
AB  - When nonlactating Holstein cows (685 +/- 59 kg) were fed chopped timothy hay (9%
      CP, 7.0 kg/d) 12 times daily, the steady-state ruminal ammonia concentration was
      2.6 mM, and the specific activity of ammonia production by mixed ruminal bacteria
      was 27.4 nmol/mg of protein-1.min-1. The addition of soybean meal (53% CP, 1 or 2
      kg/d) to the basal diet caused a linear increase in ruminal ammonia (7.0 and 12.4
      mM, respectively; P < .001), but there was only a small increase in the specific
      activity of ammonia production (30.7 and 33.8 nmol/mg of protein-1.min-1,
      respectively; P < .05). The addition of monensin (350 mg/d) to the diets caused
      more than a 30% decrease (P < .01) in ruminal ammonia at all levels of soybean
      supplementation, and there was a similar decrease (P < .001) in the specific
      activity of ammonia production. Before monensin addition, the most probable
      number of bacteria that could utilize peptides and amino acids, but not
      carbohydrates, as an energy source for growth was 5.8 to 7.0 x 10(6)/mL. When
      monensin was added to the diets, these bacteria decreased (P < .001) nearly 10
      fold. Based on these results, it seemed that monensin inhibited highly active
      amino acid-fermenting ruminal bacteria, and this inhibition, in turn, decreased
      ruminal amino acid deamination and ammonia production. Because monensin did not
      increase soluble protein, peptides, or amino acids in ruminal fluid, it did not
      seem that the decrease in ammonia increased flow of dietary amino N to the lower
      gut.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294303
TI  - Biofilms and their consequences, with particular reference to hygiene in the food
      industry.

PMID- 8294304
TI  - The survival of bacteria exposed to desiccation on surfaces associated with farm
      buildings.
AB  - The survival of 11 species of Gram-negative and Gram-positive bacteria was
      examined on different surfaces exposed to desiccation. There were large
      variations between species; Pseudomonas spp. and Rhizobium leguminosarum biovars
      survived for less than 2 d, whilst Enterococcus spp. survived for more than 11
      weeks. The type of surface on to which the bacteria were deposited affected
      survival, but with different effects between species. In addition the survival of
      spontaneous nalidixic acid-resistant (Nal-r) mutants of a natural Escherichia
      coli isolate were compared. Overall the differences were slight, but of seven
      resistant mutants, five survived better than the parent whilst one survived less
      well. Nine transposon insertion derivatives of one of the Nal-r mutants (ECO80)
      which survived better than the parent were compared; all survived similarly to
      the parent except ECO883 which survived less well. The growth characteristics of
      ECO883 and ECO80 were compared; at high osmotic pressures (> 0.4 mol 1-1 NaCl)
      ECO883 grew more slowly and showed a longer lag time than the parent. Of the
      osmoregulatory functions studied, ECO883 appeared to be altered with respect to
      K+ transport or accumulation, although the transposon insertion had occurred in a
      gene distant from known K+ transport genes.

PMID- 8294305
TI  - A modified creatine sucrose medium for differentiation of species in Penicillium
      subgenus Penicillium.
AB  - The creatine sucrose agar originally described by Frisvad was modified by varying
      the sucrose and creatine concentrations and pH over a wide range. After extensive
      tests with commonly occurring species in Penicillium subgenus Penicillium, a new
      formulation was derived, which is termed neutral creatine sucrose agar. This
      medium produced eight different reactions among the 20 species tested, and hence
      has the potential to be a very useful taxonomic medium for species in this
      difficult subgenus.

PMID- 8294306
TI  - Genetic diversity of Helicobacter pylori indexed with respect to clinical
      symptomatology, using a 16S rRNA and a species-specific DNA probe.
AB  - DNA probes are described which identify group and fingerprint strains of the
      human gastric pathogen Helicobacter pylori, on the basis of well-defined band
      homologies. A 544 bp internal fragment of the 16S ribosomal RNA gene was
      generated by polymerase chain reaction (PCR) with primers derived from the
      Escherichia coli rRNA gene sequence. In genomic Southern blots this probe
      detected restriction site variation around these loci, generating simple but
      strain-specific molecular fingerprints. A small conserved chromosomal fragment of
      1.2 kbp, Hps, species-specific for H. pylori, was obtained by cloning random
      HindIII fragments into pUC19. It was useful for dot-blot identification, and also
      separated isolates into one major and two minor groups. When results for these
      two probes were combined, a baseline characterization of genotype was obtained. A
      band-matching database of molecular fingerprints for the type strain and 63
      clinical isolates of H. pylori from asymptomatic, ulcer and gastritis contexts is
      presented. No significant association between the genotypes at this level of
      definition and the associated clinical symptomatology of the isolates was
      detected.

PMID- 8294307
TI  - Interaction between isolation source, cellular fatty acid composition and stress
      tolerance in Saccharomyces cerevisiae and its subspecies.
AB  - The physiological properties and fatty acid content of 59 strains of
      Saccharomyces cerevisiae isolated from soft-drink factories, a fruit puree
      factory, a fuel-alcohol distillery and a winery were compared. Discriminant
      analysis of the results allocated the strains to four groups according to their
      source. Resistance to preservatives and temperature stress were correlated with
      differences in fatty acid composition. The fatty acid C18: 1 delta 11, growth at
      pH 2 and in the presence of 200-600 mg l-1 benzoate or sorbate, and maximal
      growth rate at 42 degrees C were characteristics associated with yeasts from
      particular environments. However, tolerance of thermal stress and content of the
      C18: 2 fatty acid were associated with subspecies: the former species S.
      capensis, S. chevalieri, etc. The relative content of C10: 0, C12: 0 and C18: 0
      acids varied according to both isolation source and subspecies.

PMID- 8294308
TI  - Taxonomic studies on some leuconostoc-like organisms from fermented sausages:
      description of a new genus Weissella for the Leuconostoc paramesenteroides group
      of species.
AB  - Taxonomic studies were performed on some unknown Leuconostoc-like organisms from
      fermented Greek sausage. Comparative 16S rRNA sequence analysis showed the
      unidentified organisms represent a new line within the Leuconostoc
      paramesenteroides group of species. On the basis of the results of this and
      earlier phylogenetic investigations, it is proposed that Leuconostoc
      paramesenteroides and related species be reclassified in a new genus Weissella.
      In addition a new species, Weissella hellenica, is proposed for the isolates from
      fermented sausage.

PMID- 8294309
TI  - Phenotypic and phylogenetic characterization of some Gemella-like organisms from
      human infections: description of Dolosigranulum pigrum gen. nov., sp. nov.
AB  - A phylogenetic analysis was performed on two previously uncharacterized Gram
      positive, catalase-negative bacteria from clinical sources. 16S rRNA sequencing
      studies revealed the isolates represent a new line of descent within the lactic
      acid group of bacteria. On the basis of the phylogenetic findings and phenotypic
      distinctiveness of the organisms, it is proposed that they be classified in a new
      genus Dolosigranulum, as Dolosigranulum pigrum sp. nov. The type strain of
      Dolosigranulum pigrum is NCFB 2975.

PMID- 8294310
TI  - Understanding thrombin and hemostasis.
AB  - Unlike other factors in blood coagulation and fibrinolysis, thrombin has several
      functions in hemostasis from injury to recovery. Because of continual
      consumption, thrombin generation controls prethrombotic thrombin functions and
      may be prevented by inactivation of its precursors or by inhibition of thrombin
      mediated amplification steps. The direct activation product of prothrombin, alpha
      thrombin, not only converts fibrinogen into clottable fibrin but also is actively
      incorporated into the forming thrombus, where it is protected and transformed
      into other or inactive forms with thrombus maturation. Larger protein inhibitors,
      such as antithrombin III, cannot penetrate the thrombus, whereas hirudin and
      small thrombin inhibitors can. Unique structural features of thrombin allow the
      design and synthesis of a variety of small inhibitors. Such small inhibitors may
      prevent rethrombosis upon lysis of immature thrombi. On the other hand, such
      intervention must be used with caution, because low levels of thrombin appear to
      promote wound healing. In this regard, the scars of healing are but
      manifestations of the many functions of thrombin.

PMID- 8294311
TI  - A review of the hypercoagulable state.
AB  - The hypercoagulable state refers to those factors, both acquired and congenital,
      that predispose an individual to thromboembolic events. In this article, the
      major acquired and inherited conditions associated with an increased risk for
      venous thromboembolic events are critically reviewed.

PMID- 8294312
TI  - Cardiovascular and thrombosis pathology associated with cocaine use.
AB  - After decades of focus on the effects of cocaine abuse on the central nervous
      system (CNS), the cardiovascular toxicity of cocaine is just beginning to be
      appreciated. The most common cardiovascular pathologies associated with cocaine
      use include: cardiomyopathy, left ventricular dysfunction, myocarditis,
      arrhythmia, hypertension, myocardial infarction, stroke, arterial thrombosis,
      deep vein thrombosis, and gastrointestinal, renal, and skeletal muscle ischemia.
      This article reviews the above pathologies with speculations on the mechanisms by
      which cocaine produces cardiovascular tissue damage.

PMID- 8294313
TI  - Coagulation disorders in patients with monoclonal gammopathies.
AB  - Monoclonal gammopathies can present as disorders of coagulation whether the
      gammopathy is due to a malignant B-cell lymphoproliferative disorder or a
      monoclonal gammopathy of undetermined significance. Detection of the monoclonal
      gammopathy involves quantification of immunoglobulins including kappa and lambda
      along with high-resolution electrophoresis of serum. Immunofixation is
      occasionally needed on serum and always needed on urine for the final diagnosis.

PMID- 8294314
TI  - Laboratory evaluation of hemostatic disorders.
AB  - This article sketches a historical overview of milestones in diagnostic
      technologies to put into perspective a proposed role for laboratories in the
      diagnosis of coagulation disorders. Divided into five sections, the information
      presented in tables, illustrations, and appropriate vignettes for easy reference.
      The first section deals with the roles of coagulation testing in the management
      of bleeding and thrombotic disorders. Limitations of coagulation testing in
      defining the hemostatic state are discussed in the second section, and
      coagulation testing is reviewed in the third. In the fourth section
      interpretation of abnormal coagulation test results and the possible relationship
      to excessive bleeding and thrombosis are thoroughly discussed. The final section
      examines the contribution of gene analysis in establishing a diagnosis.

PMID- 8294315
TI  - Diagnostic approaches and surgical treatment of deep venous thrombosis and
      pulmonary embolism.
AB  - Diagnostic approaches for thromboembolism include Doppler probe examination,
      impedance plethysmography, phleborheography, radio-labeled fibrinogen scanning,
      magnetic resonance imaging, duplex imaging, and venography. The two primary
      diagnostic approaches for pulmonary embolism include ventilation/perfusion lung
      scanning and pulmonary arteriography. Surgical options available for venous
      thromboembolism are generally limited to those condition in which limb viability
      is threatened from acute iliofemoral thrombosis. Vena caval interruption,
      performed in patients with a contraindication to anticoagulation, a complication
      during anticoagulant therapy, and recurrent pulmonary embolism in the presence of
      adequate anticoagulation (among other indications) is best accomplished with the
      Greenfield filter. Surgical approaches for pulmonary embolism, limited to
      patients with massive embolism with hypotension, include catheter pulmonary
      embolectomy and open pulmonary embolectomy.

PMID- 8294316
TI  - Current management of hemophilia B.
AB  - The management of hemorrhagic episodes in patients with hemophilia B is in
      transition as a result of the availability of new products for replacement
      therapy. Although the basic principles of therapy have not changed, the new
      highly purified Factor IX concentrates, AlphaNine and Mononine, represent a break
      through, as they appear to be safe in terms of viral transmission and
      thromboembolic side-effects. These products are now widely available, and
      although expensive, are regarded by some physicians as the preferred therapy for
      Hemophilia B. Less pure and less expensive Factor IX products, however, are also
      available and can be used safely in previously treated patients who have already
      been exposed to the hepatitis viruses.

PMID- 8294317
TI  - Managing the hemorrhagic complications of heparin therapy.
AB  - Heparin provides a powerful therapeutic ally for the clinician challenged by
      patients with thromboembolic disorders. A wide range of complications, however,
      has been observed in patients receiving heparin for thromboembolic disorders
      considered to be serious or life-threatening. This article addresses the
      management of heparin-associated bleeding. In doing so, the author examines the
      factors affecting levels of heparin that could lead to inappropriate or excessive
      administration--namely, heparin metabolism, heparin administration, laboratory
      monitoring, and a major contributing complication, heparin-induced
      thrombocytopenia. Unfortunately, attempts to manage anti-coagulant bleeding in
      the presence of thrombosis can often create additional difficulties that continue
      to challenge the clinician.

PMID- 8294318
TI  - Warfarin-induced skin necrosis.
AB  - Warfarin-induced skin necrosis is a rare but potentially devastating complication
      of oral anticoagulation. In this article the historical, clinical, and
      pathophysiologic features of this hypercoagulable event are reviewed, and
      recommendations for prevention and treatment are discussed.

PMID- 8294319
TI  - Scleroderma, the heart and myocardial Raynaud's phenomenon.

PMID- 8294320
TI  - Catching the worm: better late than never.

PMID- 8294321
TI  - Cardiac involvement in systemic sclerosis.
AB  - The clinical profile of systemic sclerosis with screening for cardiac involvement
      and the effect of cold stimulation on myocardium are described in 17 patients.
      Besides routine investigations, echocardiography, radionuclide ventriculography
      and computerized stress test, both before and after cold pressor test were done.
      Ten patients had abnormal ECG findings, two patients had mild pericardial
      effusion and five patients had moderate grade pulmonary hypertension.
      Echocardiography and radionuclide ventriculography did not reveal wall motion
      abnormality either before or after cold stimulation. Computerized stress test was
      positive for ischaemia following cold stimulation in one patient.

PMID- 8294322
TI  - Stomach in portal hypertension.
AB  - 365 consecutive patient of portal hypertension [Cirrhosis 285, Non-cirrhotic
      portal fibrosis (NCPF) 50, Extrahepatic portal vein obstruction (EHPVO)-30] were
      evaluated prospectively over a period of 2 years. Of these, 33 patients underwent
      successful sclerotherapy with evaluation before and after the same. Portal
      hypertensive gastropathy (PHG) was found in 56.4% (mild 28.2%, Severe 28.2%) of
      total patients; while its incidence was 60.6% in cirrhosis, 54% in NCPF and 20%
      in EHPVO. Incidence of PHG was significantly higher in cirrhotics when compared
      with non-cirrhotics (60.7% vs 41.25%: p < 0.05). PHG is more common in patients
      with large esophageal varices as compared to those with small varices (64.1% vs
      50.8%: p < 0.05). Overall incidence of gastric varices was 29.3% while its
      incidence in cirrhosis, NCPF and EHPVO was 22.1%, 44% and 73.3% respectively.
      Incidence of gastric varices was significantly higher in non-cirrhotics (NCPF +
      EHPVO) when compared with cirrhotic (p < 0.05) and in patients with large
      esophageal varices when compared with patients having small esophageal varices (p
      < 0.05). Peptic ulcer was found in 10.9% patients with portal hypertension. (More
      than 90% were cirrhotics, mainly alcoholics). 33 patients underwent successful
      sclerotherapy of which 11 had PHG (mild--6, severe--5) at the beginning of
      sclerotherapy. After successful sclerotherapy 26 patients had PHG (mild--14,
      severe--12) p < 0.001). There was no significant difference in incidence of
      gastric varices before and after sclerotherapy. Incidence of PHG was
      significantly higher in cirrhotics while gastric varices were seen more commonly
      in patients with non-cirrhotic portal hypertension.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8294323
TI  - Immunological study in pleural effusion.
AB  - Thirty patients of pleural effusion (25 tubercular, 5 malignant) were studied for
      enumeration of T and B cell percentage in pleural fluid (PF) and peripheral blood
      (PB) along with estimation of IgG, IgA and IgM. Ten healthy subjects were taken
      as controls. T cell percentage was significantly low and B cell percentage high
      in the PB of patients with effusion compared with controls. Comparing malignancy
      and tuberculosis patients it was seen that in both T cells in PF were higher and
      B cells lower compared with their respective values in PB. Significantly
      increased percentage of T cells in PF indicates either an active sequestration in
      PF or the presence of suppressor adherent cells in PB. However, T and B cell
      percentage in PB and PF were not significantly different in the two study groups.
      PB immunoglobulin (IgG, IgA, IgM) levels in patients were higher as compared to
      those in the controls, without significant difference in their levels in the two
      study groups. Ratio of PF/PB values for various immunoglobulins was less than
      unity but a cut-off point of 0.6 for IgG & IgA and 0.5 for IgM worked out as
      pointer for differentiating between malignant and tubercular effusions.

PMID- 8294324
TI  - Ascitic fluid cholesterol in differential diagnosis of ascites.
AB  - Cholesterol was estimated in ascitic fluid of 89 patients (29 malignant and 60
      non-malignant ascites). Mean ascitic cholesterol level was significantly higher
      in malignant ascites (89.52 mg/dl) as compared to non-malignant ascites (29.93
      mg/dl). At a cut off value of 48 mg/dl, the sensitivity, specificity, positive
      and negative predictive value and overall diagnostic accuracy for diagnosing
      malignant ascites is 96.5%, 96.6%, 93.3%, 98.3% and 96.6% respectively. Ascitic
      fluid cholesterol estimation is an easy and reliable test for differentiating
      malignant ascites from non-malignant ascites.

PMID- 8294325
TI  - Heterotopic gastric mucosa and Helicobacter pylori infection in Meckel's
      diverticulum in Indian subjects.
AB  - Two of twenty nine (6.8%) patients who had undergone resection of Meckel's
      diverticulum demonstrated heterotopic gastric mucosa. In both these patients
      gastric mucosa was of antral type. Remaining 27 of 29 (93.2%) patients with
      Meckel's diverticulum had intestinal mucosa. 9 of 29 (31%) patients with Meckel's
      resected were symptomatic (8 bleeding, 1 perforation) and all 9 were negative for
      heterotopic gastric mucosa. Helicobacter pylori (H. pylori) was absent in both
      patients with intestinal mucosa. Antral biopsy from 13 partial gastrectomy
      specimens (surgery done for carcinoma stomach) were used as methodological
      controls and 7 of 13 (54%) showed H. pylori colonization. We conclude that (i)
      incidence of gastric mucosa is 6.8% in Meckel's diverticulum in our population,
      (ii) presence of heterotopic gastric mucosa is unlikely to be associated with
      complications of Meckel's diverticulum and (iii) heterotopic mucosa in Meckel's
      diverticulum is not commonly colonized by H. pylori.

PMID- 8294326
TI  - Evaluation of QRS score as an index of infarct size and prognosis.
AB  - Present study comprises of 44 patients with Acute Myocardial Infarction. Their
      QRS score was correlated with Infarct Size by estimating the CPKMB levels and the
      post infarction complications during hospital stay. A statistically significant
      correlation was found between the 2 parameters of QRS score and infarct size (r =
      0.75). It was better in anterior wall infarction (r = 0.96) than in inferior wall
      infarction (r = 0.64). The interobserver agreement between 2 observers for QRS
      score was excellent (rho = 0.99) QRS score was found to be a good prognostic
      indicator in the post infarction phase.

PMID- 8294327
TI  - Observation of lipid profile and lipoproteins in viral hepatitis and hepatic
      coma.
AB  - Lipid profile and lipoprotein levels were estimated in 35 patients of viral
      hepatitis, 15 patients of viral hepatitis with coma and in age and sex match 35
      healthy controls. The values were compared in different groups. Levels of
      triglycerides were significantly raised (145.00 +/- 30.70 mg/dl) in viral
      hepatitis as compared to viral hepatitis with coma (111.40 +/- 16.80 mg/dl) which
      were similar to controls (110.8 +/- 20.6 mg/dl). Patients who recovered had
      higher levels of triglycerides (136.0 +/- 30.8 mg/dl) as compared to those who
      expired (110 +/- 15.72 mg/dl). Total serum cholesterol remained statistically
      unaltered in both groups. HDLc was significantly decreased in both groups, viral
      hepatitis (2.23 +/- 6.7 mg/dl) and viral hepatitis with coma (16.52 +/- 2.27
      mg/dl) in comparison to controls (62.21 +/- 18.04 mg/dl). The levels were much
      lower in patients with coma than without coma. Furthermore the values were still
      lower in patients who expired (15.82 +/- 2.27 mg/dl) than in patients who
      recovered (24.13 +/- 7 mg/dl). The levels of LDLc were significantly raised in
      both groups, as compared with each other and in relation to mortality. VLDLc
      levels were significantly decreased in patients of viral hepatitis (22.13 +/- 5.8
      mg/dl) as well as on viral hepatitis with coma (21.89 +/- 4.3 mg/dl). However, no
      significant difference was observed when compared with each other and in relation
      to mortality. Thus it may be concluded that isolated low value of HDLc in viral
      hepatitis may be used as a prognostic indicator.

PMID- 8294328
TI  - Zinc in rheumatic heart valves.
AB  - This study included 48 patients with chronic rheumatic heart disease, 60 control
      subjects for plasma zinc comparison and 20 control specimens of heart valves from
      postmortem cases of accident deaths. Plasma and cardiac tissue levels of zinc in
      patients with rheumatic heart disease were significantly lowered compared to
      controls. Since zinc is important in the synthesis of nucleic acids and proteins
      it may influence tissue growth, reparative process and structure and function of
      biomembrane. Low zinc levels may also influence cell mediated immunity and may
      increase susceptibility of patients to infection and increased rheumatic activity
      which needs further study.

PMID- 8294329
TI  - Nifedipine induced modulations of intra-thyroidal radio-iodine turnover kinetics
      in euthyroid and thyrotoxic patients.
AB  - Nifedipine induced modulations of intrathyroidal radioiodine turnover kinetics
      has been studied in euthyroid and thyrotoxicosis individuals. Nifedipine has been
      found to suppress Amax significantly (p < 0.001), while transit kinetics k1 and
      k2 are not significantly affected. On the contrary, in the patients with
      thyrotoxicosis post-nifedipine Amax was not significantly different from pre
      nifedipine study, while k1 was slightly suppressed (p < 0.05) and k2 was
      significantly elevated (p < 0.01). Apparently different Ca+2 dependent control
      mechanisms are operative in euthyroid and thyrotoxic states. Clinical
      implications of these observations have been discussed.

PMID- 8294330
TI  - Amlodipine in mild and moderate hypertension: initial Indian experience.
AB  - In an open, non-comparative, variable-dose study, 20 outpatients with mild to
      moderate essential hypertension were treated with 5-10 mg amlodipine once daily
      for 4 weeks, after their blood pressures had stabilized on placebo. Amlodipine
      produced a significant decrease in blood pressure (P < 0.05) from the initial
      mean of 162/100 mm Hg to 139/85 mm Hg at 4 weeks. 80% of the patients reached the
      goal diastolic blood pressure of < or = 90 mm Hg with a once-daily dose of 5 mg
      amlodipine within 2 weeks. The remaining 20% also attained the goal diastolic
      blood pressure within 4 weeks, with a one-step increase in the dose to 10 mg at 2
      weeks. Amlodipine maintained blood pressure reduction throughout the 24-hours
      dosing interval with a once-daily dose. Notably, no side effects were observed;
      pulse rate, electrocardiogram, and laboratory parameters were not significantly
      altered with therapy. Amlodipine in a single daily dose of 5-10 mg is effective
      and well tolerated in the treatment of patients with mild to moderate
      hypertension.

PMID- 8294331
TI  - HLA-disease association at the molecular level.

PMID- 8294332
TI  - Abdominal pain and fever in cirrhotic patients.

PMID- 8294333
TI  - Clinical symptoms in diagnosing a rare renal mass.

PMID- 8294334
TI  - Chloramphenicol resistant enteric fever complicated by disseminated intravascular
      coagulation and sensitive to ciprofloxacin.

PMID- 8294335
TI  - Hypoglycaemic hemiplegia due to insulinoma.

PMID- 8294336
TI  - Combined toxicity due to alcohol and aluminium phosphide.

PMID- 8294337
TI  - Duane's retraction syndrome with facial hemiatrophy.

PMID- 8294338
TI  - Chronic ischaemic monomelic neuropathy.

PMID- 8294339
TI  - Subcutaneous sparganosis--a rare infection in man.

PMID- 8294340
TI  - An uncommon source of right sided endocarditis.

PMID- 8294341
TI  - Plasmodium falciparum or dengue fever?

PMID- 8294342
TI  - ST-T changes following tobacco creamy snuff used as toothpaste.

PMID- 8294343
TI  - False positive treadmill test with preexcitation syndrome.

PMID- 8294344
TI  - Valsalva manoeuvre--some more facts.

PMID- 8294345
TI  - Colchicine in type II diabetes.

PMID- 8294346
TI  - Screening for asymptomatic glycosuria.

PMID- 8294347
TI  - Vibrio mimicus.

PMID- 8294348
TI  - Changing concepts of IgA nephropathy.

PMID- 8294349
TI  - Acute diarrhoea caused by Vibrio mimicus in Calcutta.
AB  - Out of 539 acute diarrhoea cases studied, Vibrio mimicus was isolated as a sole
      pathogen in the faeces of 7 (1.3%) cases. The chief clinical presentations of the
      seven cases were watery diarrhoea and vomiting. Bloody diarrhoea was observed in
      2 (28.5%), abdominal pain in 2 (28.57%) and fever in one (14.29) cases. All cases
      could be effectively treated with ORS except 3 (42.85%) cases who required IV
      Ringer's lactate. All V. mimicus strains isolated in the study were uniformly
      susceptible to tetracycline, chloramphenicol, norfloxacin and ciprofloxacin.

PMID- 8294350
TI  - Primary IgA nephropathy in adults.
AB  - IgA nephropathy was found in 9.6% of 649 adults with primary glomerulonephritis.
      Hypertension was detected in 51.6% and renal failure in 32.3%. A nephrotic
      presentation was seen in 22.6% and recurrent macroscopic hematuria in 17.7%. On
      light microscopy, mesangial hypercellularity and an increase in mesangial matrix
      were frequently seen (74.2%). Immunofluorescence studies demonstrated IgA in all
      patients along with C3 in 61.3%, IgM in 27.4% and IgG in 11.3%. Followup was
      possible in 61.3% for mean period of 17.3 months. No clinical or biochemical
      abnormalities were detected on followup in 26.3%. Progression to end stage renal
      disease was noted in 7.9%.

PMID- 8294351
TI  - Multiple system organ failure: a study of outcome.
AB  - One hundred patients with Multiple System Organ Failure (MSOF) were studied. The
      precipitating factors were infections, poisoning, metabolic disorders, surgical
      disorders and cardiac arrest resulting in an overall mortality of 65%. Mean
      inpatient stay was 3.86 days, being significantly longer in patients who survived
      (6.25 days). Age, sex, addictions and premorbid health did not affect outcome.
      GIT (89%), CNS (81%) and Liver failure (62%) were seen most commonly. Highest
      mortalities were observed with RS (81.2%), CVS (80.37%) and CNS (76.5%). The
      mortality with 2,3,4,5,6 and 7 OSF was 8.3%, 18.7%, 70%, 92%, 100% and 100%
      respectively. The mortality was highest (50.76%) on the first day of MSOF and
      during the initial 48 hours of the total duration of disease. The method proposes
      an easily reproducible way to evaluate severity of illness and predicting outcome
      in acute MSOF.

PMID- 8294352
TI  - Study of acute mountain sickness during "rapid ascent" trekking to extreme
      altitude.
AB  - Acute mountain sickness (AMS) is an important cause of morbidity and mortality
      following acute exposure to high altitude. Several clinical variables were
      evaluated during the 1990 Trans-Kalindi Exploration to extreme altitude (5949 m)
      in 10 healthy adult lowlanders (age 31.7 +/- 6.4 yrs) who undertook a relatively
      rapid ascent from sea level to 5949 m with short periods of acclimatisation at
      4393 m, 4898 m and 5700 m. 40% of the subjects had definite AMS. Only one subject
      had features of early cerebral oedema at 4393 m and had to be brought down
      temporarily to 3878 m. All subjects completed the trek without needing
      medication. Proper acclimatisation was characterised by absence of significant
      symptoms of AMS above 4500 m, absence of sustained tachycardia, fall in daily
      positive fluid balance from 1.7 +/- 0.9 (sea level) liters to 0.7 +/- 0.3 litres
      (at 5700 m) (p < 0.05), increase in 24 hours urinary sodium excretion from 174 +/
      78 mmol to 344 +/- 145 mmol (p < 0.01) and an increase in the ratio of urinary
      excretion of sodium and potassium from 3.1 (sea level) to 3.6 (5700 m). We
      conclude that the incidence of AMS at extreme altitude is similar to that at
      lower altitude. Reasonable acclimatisation is possible during the climb to
      extreme altitude.

PMID- 8294353
TI  - Delta virus infection in cirrhotics in a north Indian hospital.
AB  - Forty patients of HBV related cirrhosis of the liver were studied for the
      presence of delta infection and subsequently the clinical features, course and
      outcome of these delta infected cases was compared with those of delta uninfected
      cases. Out of 40 patients studied, only four patients (10%) were reactive for
      anti-delta antibodies. The incidence of delta infection was common in the younger
      age group (31.25 +/- 4.78 years) as compared to the older age group (48 +/- 7.25
      years) at p < 0.001. Hepatic Encephalopathy was seen in only 13.88% of delta
      negative patients as compared to 75% of delta infected patients (p < 0.05).
      During follow up period of 1 year, 75% of patients died in the delta virus
      infected group as compared to 22.22% in the delta negative group. The mortality
      was significantly higher in Child's class C (P < 0.01). So delta virus infection
      is associated with a more severe course of illness and a poorer prognosis in HBV
      related cirrhotics.

PMID- 8294354
TI  - Clinical evaluation of halofantrine in acute malaria.
AB  - Fifty patients suffering from acute malaria were treated with 'Halofantrine
      Hydrochloride'. They were observed for 4 weeks. Clinical, haematological and
      biochemical parameters were assessed for evaluation of halofantrine in acute
      malaria, with special reference to its effectiveness, tolerability and side
      effects.

PMID- 8294355
TI  - Efficacy and safety of halofantrine in acute malaria.
AB  - Clinical trial of halofantrine was conducted in 32 cases of acute malaria. Twenty
      four patients with P. vivax and eight patients with P. falciparum infection were
      treated with 3 doses of halofantrine (500 mg each) orally, after food, at
      intervals of 6 hours. Mean parasite clearance time of P. vivax was 57.75 h and
      for P falciparum 75 h and mean defervescence time was 31.08 h and 34 h
      respectively. Post treatment followup was for 28 days. Clinical symptoms related
      to malaria cleared within the first 48 h. Mild adverse reactions of abdominal
      pain in one patient and vomiting in one patient were encountered which did not
      require any treatment. Halofantrine was found to be very effective and free from
      significant adverse events when used for the treatment of acute malaria.

PMID- 8294356
TI  - Q-wave and non-Q wave myocardial infarction--prospective study.
AB  - Fifty patients each of Q-wave myocardial infarction (QMI) and non-Q-wave
      myocardial infarction (NQMI) were studied clinically and followed up for one
      year. Significant differences were observed between the two groups concerning the
      mean age (higher in NQMI, p < 0.05), sex (more females in NQMI, p < 0.01),
      location of the infarct (inferior in QMI and anterolateral in NQMI, p < 0.01),
      past ischaemic episodes (higher in NQMI, p < 0.001), post infarction ischaemic
      episodes (higher in NQMI, p < 0.05), early mechanical and electrical
      complications (higher in QMI, p < 0.05), peak serum enzyme levels (higher in QMI,
      p < 0.05) and both early mortality (higher in QMI, p < 0.05) and subsequent
      mortality rates (higher in NQMI, p < 0.05). The total one year mortality was
      similar in both the groups (30%). When only anterolateral infarctions were
      considered longterm prognosis for QMI patients was worse than that of NQMI
      patients (65% vs 37.5%, p < 0.05). Contrariwise, irrespective of the type of
      infarction, QMI or NQMI, anterolateral infarction resulted in higher mortality
      than inferior wall infarction (46.7% vs 5% p < 0.001).

PMID- 8294357
TI  - Complications in 1000 consecutive treadmill tests.
AB  - Complication in 1000 consecutive Tread Mill Tests (TMT) done at the Cardiology
      Centre of Command Hospital (SC) Pune are reported. The tests were done following
      Bruce Protocol and analysed based on Selzer's criteria. Complications were noted
      in 18 cases (1.8%) which included ventricular fibrillation, ventricular
      tachycardia, atrial fibrillation, malignant VPBs, conduction disturbances,
      asystole following hyperventilation (HV), complete SA block following HV, atrial
      flutter following HV, hypotension and severe angina requiring ICCU care. No acute
      myocardial infarctions or deaths were noted. Coronary arteriography (CART) was
      done in 50 (5.0%) selected cases including 10 with complications. It is concluded
      that TMT is a safe procedure if carried out after proper patient selection and
      under supervision of an experienced and efficient team.

PMID- 8294358
TI  - Zinc in human health and disease.

PMID- 8294359
TI  - Splenic aspiration in kala-azar.

PMID- 8294360
TI  - Young's syndrome--a rare cause of bronchiectasis.

PMID- 8294361
TI  - Chronic limb girdle myasthenia gravis.

PMID- 8294362
TI  - Progressive systemic sclerosis and cancer breast: does an association exist?

PMID- 8294363
TI  - Fascicular tachycardia--more unfamiliar than uncommon. A report of two cases.

PMID- 8294364
TI  - Mechanisms of orthostatic hypotension in progressive autonomic failure.

PMID- 8294365
TI  - Primary hyperparathyroidism in an adolescent girl manifesting as rickets.

PMID- 8294366
TI  - Chloramphenicol resistant Salmonella meningitis in adults--a report of 3 cases.

PMID- 8294367
TI  - Phenytoin toxicity due to rifampicin induced hepatic dysfunction.

PMID- 8294368
TI  - Hypernephroma (renal cell carcinoma) with tumour extension to right atrium in an
      asymptomatic patient.

PMID- 8294370
TI  - Involvement of nails in discoid lupus erythematosus.

PMID- 8294369
TI  - Hyperthyroidism induced remission in type II diabetes.

PMID- 8294371
TI  - Amoebic liver abscess--an unusual presentation.

PMID- 8294372
TI  - Effect of hyperventilation and exercise on right sided chest leads in normal
      persons.

PMID- 8294373
TI  - Upper esophageal spasm in systemic sclerosis.

PMID- 8294375
TI  - The osteoporosis pseudoglioma syndrome.
AB  - The diagnosis of osteoporosis pseudoglioma syndrome was established by
      radiological study in two children who were previously diagnosed as having
      osteogenesis imperfecta. The clinical, radiological and biochemical findings are
      discussed. The important role of radiology in establishing the diagnosis is
      stressed.

PMID- 8294374
TI  - [Pneumatosis cystoides intestinalis revisited].
AB  - Two cases of pneumatosis cystoides coli are reported. The authors present an
      anatomic and physiopathologic review of the entity and give the list of
      etiologies with the worse prognosis. The radiologic signs are described and their
      contribution to an accurate diagnosis is stressed, as it may avoid useless
      surgical interventions.

PMID- 8294376
TI  - Contribution of MRI and color Doppler sonography in breast cancer diagnosis.
AB  - Thirty female patients were examined with both MRI (30) and color Doppler
      sonography (24). MRI after injection of Gadolinium DTPA in combination with fast
      3D FLASH sequences makes it possible to plot out signal-intensity changes over a
      certain period of time. Flow within a malignant breast lesion can be depicted
      with color Doppler sonography. The signal intensity increase pattern over a
      period of time, and the detection of color Doppler flow are of major importance
      for the differential diagnosis in breast cancer.

PMID- 8294377
TI  - Neuropathic arthropathy of the shoulder secondary to syringomyelia.
AB  - Many neurological disorders can lead to neuropathic arthropathy. When severe, the
      radiographic changes are virtually pathognomonic: joint disorganization is more
      profound than in any other arthropathy. Neuroarthropathy of the shoulder is most
      frequently seen in syringomyelia and can be the presenting symptom or the symptom
      leading to the--previously unrecognized--diagnosis. Such a case is presented.

PMID- 8294378
TI  - Xanthogranulomatous pyelonephritis in a child.
AB  - Xanthogranulomatous pyelonephritis is an uncommon form of chronic aggressive
      infection of the kidney and surrounding tissues usually affecting middle aged
      women. It is rarely seen in childhood. We report the case of a female child with
      a history of fatigue, progressive anorexia, and fever in whom a diagnosis of
      pyelonephritis on a predisposing factor of lithiasis was suggested. After initial
      antibiotic treatment, nephrectomy was needed for an acute general deterioration.
      Pathology demonstrated xanthogranulomatous pyelonephritis.

PMID- 8294379
TI  - [Meigs' syndrome].
AB  - Ascites and pleural effusion associated with "fibroma-like ovarian" benign tumor
      is described as Meigs syndrome. Tumor extirpation resulted in ascites and pleural
      effusion resorption. This rather unusual syndrome, should not be overlooked.

PMID- 8294380
TI  - [Imaging of breast cancer in men].

PMID- 8294381
TI  - Lingual thyroid imaging.
AB  - Lingual thyroid is the most frequent benign mass found at the junction of the
      anterior two-thirds and posterior one-third of the tongue. MR has become the best
      non-invasive technique to make the diagnosis because it allows multiplanar
      imaging and provides the best soft tissue definition. Aberrant primitive vascular
      supply is often present and therefore angiography remains necessary because
      precise knowledge of the vascular supply is mandatory prior to embolisation,
      ligation, or operation.

PMID- 8294382
TI  - Double gallbladder documented by endoscopic retrograde cholangiography.
AB  - A case of trabecular type of gallbladder duplication, a very rare congenital
      anomaly of the gallbladder, is reported. Diagnosis was made by endoscopic
      retrograde cholangiography and was confirmed by oral cholecystography. Sonography
      could not visualize the accessory gallbladder.

PMID- 8294383
TI  - Mesenteric involvement of thromboangiitis obliterans (Buerger's disease) in a
      woman.
AB  - Although patients with peripheral arterial occlusive disease due to
      thromboangiitis obliterans (TAO) have been well characterized and the
      relationship of this disease to tobacco is stressed, little attention has been
      focused on its ability to involve the mesenteric vasculature and its ability to
      affect women. We report a rare case of a known TAO female patient who presented
      with abdominal pain due to inflammatory changes of the mesenteric vessels. The
      resulting small bowel ischemic changes and formation of intramural gas were
      demonstrated on a small bowel follow-through and a plain abdominal film. An
      angiography finally showed a superior mesenteric artery occlusion.

PMID- 8294384
TI  - Gastroenteric cyst.
AB  - The authors report a rare case of gastroenteric cyst in a 4-day-old baby with
      increasing cyanosis. CT and MRI demonstrated a posterior mediastinal cystic mass,
      which finally was characterised by pathology as a gastroenteric cyst.

PMID- 8294385
TI  - Intracerebral primitive neuro-ectodermal tumor (PNET).
AB  - A case of intracerebral primitive neuro-ectodermal tumor (PNET) is presented.
      PNETs are rare, undifferentiated neoplasms occurring primarily in children and
      young adults. These tumors exhibit a highly malignant behaviour with a tendency
      to disseminate along the cerebrospinal fluid (CSF) pathways. Preoperative
      diagnosis is difficult, owing to the non-specific CT and MR appearances and to
      the rarity of this tumor. Our patient was 33 years old, which is uncommon. CT
      findings initially suggested an intracerebral hematoma. Later on, CT and MR
      findings were specific for a brain tumor and showed a solid, non-calcified
      invasive mass, with poor perilesional edema.

PMID- 8294386
TI  - Characteristics of desipramine-refractory depression.
AB  - BACKGROUND: To determine the predictors of desipramine-refractory depression, the
      authors examined the outcome in patients with major depression who were admitted
      to a general hospital and treated with desipramine adjusted to an adequate blood
      level. METHOD: Sixty-eight consecutive inpatients with DSM-III nonpsychotic
      unipolar major depression who had failed to respond to 1 week of hospitalization
      without drug treatment were studied. Outcome was assessed with the Yale
      Depression Inventory after a 4-week desipramine trial in which 24-hour plasma
      concentrations were used to rapidly achieve a therapeutic desipramine level.
      RESULTS: Poor response to a therapeutic desipramine trial, which occurred in 15
      of 50 patients, was significantly associated with definite personality disorder,
      prior treatment failure, near delusional status, age < or = 35 years, duration of
      depressive episode, recurrence of depression, dysthymia, and secondary
      depression. The first four items remained significantly correlated with poor
      response when the presence of the other items was accounted for using multiple
      regression. Drug response was not predicted by the diagnosis of melancholia (DSM
      III and DSM-III-R) or initial severity of the depressive episode. CONCLUSION: The
      four strongest correlates of outcome were highly predictive of drug response. In
      patients with two or more predictors, only 25% (4 of 16) responded, while in
      those with one or no predictors, 91% (31 of 34) responded.

PMID- 8294387
TI  - Lorazepam treatment of acute and chronic catatonia in two mentally retarded
      brothers.
AB  - BACKGROUND: Acute catatonia of the retarded type responds rapidly to treatment
      with lorazepam. There is little information about (1) the efficacy of
      benzodiazepines in patients with longstanding catatonic syndrome; (2) the effect
      of longer-term lorazepam therapy in catatonic patients who do not respond to a
      brief trial of the medication; and (3) the development of catatonic syndromes in
      family members. METHOD: We gave lorazepam to two mentally retarded brothers with
      catatonia. One had become catatonic 2 weeks before starting treatment while the
      other had been hospitalized in a catatonic state for 5 years. RESULTS: The
      brother with acute catatonia recovered slowly but completely within 2 weeks of
      starting lorazepam. The brother with long-standing catatonia responded gradually
      during the first 5 months of treatment and required higher doses of lorazepam but
      did eventually recover and was discharged from the hospital on a regimen of
      lorazepam after 1 year of treatment. CONCLUSION: (1) Lorazepam may be effective
      even in patients who have been catatonic for years. (2) Catatonic patients who do
      not recover immediately with lorazepam may respond to a longer course or higher
      doses of the medication. (3) There may be a familial predisposition to developing
      catatonia in response to stressful situations.

PMID- 8294388
TI  - Combined SSRI-moclobemide treatment of psychiatric illness.
AB  - BACKGROUND: To determine the efficacy and safety of a serotonin selective
      reuptake inhibitor (SSRI) combined with moclobemide in the treatment of 11
      patients with various DSM-III-R diagnoses. METHOD: Subjects received moclobemide
      in doses of 150 to 800 mg/day together with sertraline (N = 5) in doses of 25 to
      200 mg/day or fluvoxamine (N = 6) in doses of 50 to 200 mg/day. Patients were
      carefully monitored for side effects and for clinical response at the end of the
      trial, which lasted a minimum of 5 weeks. RESULTS: The combination was tolerated
      extremely well. Insomnia was the most common side effect, occurring in 5 of 11
      subjects. A marked or complete therapeutic response was noted in 8 of 11
      subjects. CONCLUSION: This open clinical trial suggests that combined SSRI
      moclobemide treatment appears to be safe and well tolerated. It may also have
      therapeutic effects in treatment-refractory patients.

PMID- 8294389
TI  - Serotonin reuptake blockers for the treatment of obsessional jealousy.
AB  - BACKGROUND: Some patients with pathological jealousy have a predominant
      obsessional component to their jealous thoughts. Since obsessions and compulsions
      often respond to serotonin reuptake blockers, these agents may also be useful for
      obsessional jealousy. METHOD: We undertook a retrospective study of patients who
      presented with obsessional jealousy. Six patients were treated in open clinical
      practice with serotonin reuptake blockers. RESULTS: Four of the six patients
      responded to medication. This response was as robust as that seen in patients
      with classical symptoms of obsessive compulsive disorder. CONCLUSION: Obsessional
      jealousy has phenomenological similarities to other obsessions and compulsions,
      and obsessional jealousy may also respond to standard antiobsessional
      medications.

PMID- 8294390
TI  - The Fifth Psychoactive Drug Usage Guide.

PMID- 8294391
TI  - Trichotillomania and body dysmorphic disorder.

PMID- 8294392
TI  - Potassium supplementation during lithium therapy.

PMID- 8294393
TI  - Possible therapeutic window for serotonin reuptake inhibitors.

PMID- 8294394
TI  - An apparent neurotoxicity associated with clozapine.

PMID- 8294395
TI  - Compulsive buying: descriptive characteristics and psychiatric comorbidity.
AB  - BACKGROUND: Compulsive buying is infrequently described in the psychiatric
      literature despite suggestions that it may be prevalent. The authors investigated
      the demographics and phenomenology of this syndrome and assessed psychiatric
      comorbidity via interviews of both compulsive buyers and normal buyers. METHOD:
      Twenty-four compulsive buyers were compared with 24 age- and sex-matched normal
      buyers using (1) a semistructured interview for compulsive buying and impulse
      control disorders, (2) a modified version of the Structured Clinical Interview
      for DSM-III-R, and (3) scales measuring compulsiveness, depression, and anxiety.
      RESULTS: The typical compulsive buyer was a 36-year-old female who had developed
      compulsive buying at age 17 1/2 and whose buying had resulted in adverse
      psychosocial consequences. Purchases were usually of clothes, shoes, jewelry, or
      makeup, which frequently went unused. Compared with normal buyers, compulsive
      buyers had a higher lifetime prevalence of anxiety disorders, substance use
      disorders, and eating disorders and were more depressed, anxious, and compulsive.
      Among compulsive buyers, 16 (66.7%) described buying that resembled obsessive
      compulsive disorder, whereas 23 (95.8%) described buying that resembled an
      impulse control disorder. CONCLUSION: Compulsive buying is a definable clinical
      syndrome that can result in significant psychosocial impairment and which
      displays features of both obsessive compulsive disorder and the impulse control
      disorders.

PMID- 8294396
TI  - Rh-related antigen CD47 is the signal-transducer integrin-associated protein.
AB  - Integrin-associated protein (IAP) is a 50-kDa membrane protein with an amino
      terminal immunoglobulin domain and a carboxyl-terminal multiply membrane-spanning
      region. It is physically and functionally associated with the integrin alpha v
      beta 3 vitronectin receptor and is involved in the increase in intracellular
      calcium concentration, which occurs upon cell adhesion to extracellular matrix.
      Oxidative burst in neutrophils can be induced or inhibited via IAP. Surprisingly,
      IAP is also expressed on erythrocytes, which have no known integrins. IAP has
      been shown to be identical to OA3, an ovarian carcinoma antigen. We now show that
      IAP expression is reduced on Rhnull erythrocytes. The IAP structural gene is
      mapped to q13.1-2 on human chromosome 3, within a region known to contain a gene
      encoding the Rh-associated 1D8 antigen. By expression studies on human
      erythrocytes and IAP transfectants, IAP is shown to be identical to the 1D8
      antigen and to CD47, a cell surface protein with broad tissue distribution,
      reduced in expression on Rhnull erythrocytes. Two CD47 antibodies recognize the
      immunoglobulin domain of IAP, as does antibody 1D8. These studies suggest the
      possibility that IAP and the Rh polypeptides may share a pathway for membrane
      expression on erythrocytes. Furthermore, decreased expression of IAP on Rhnull
      cells may contribute to the these cells' abnormal cation permeabilities. These
      studies demonstrate an unexpected link between integrin signal transduction and
      erythrocyte membrane structure.

PMID- 8294397
TI  - Hybrid tyrosine kinase/cytokine receptors transmit mitogenic signals in response
      to ligand.
AB  - While much is known about the mechanisms by which members of the receptor
      tyrosine kinase family effect mitogenic signal transduction, much less is known
      about such mechanisms for members of the hematopoietic cytokine receptor family.
      In an effort to determine the extent to which the signal transduction mechanisms
      of these two receptor families may be related, we constructed and tested
      interfamily hybrid receptors. Two hybrid receptors consisting of the ligand
      binding domain of the epidermal growth factor receptor (EGFR) fused to the
      transmembrane and cytoplasmic domains of the erythropoietin receptor (EPOR), as
      well as the parental EPOR or EGFR, were introduced into interleukin-3-dependent
      32D cells. Part of the EPOR extracellular region containing a conserved WSXWS
      amino acid motif was present in one of the hybrid receptors but not in the other.
      Cells expressing EGFR grew only poorly in response to EGF, whereas cells
      expressing either of the EGFR/EPOR hybrid receptors or EPOR grew robustly in
      epidermal growth factor or erythropoietin, respectively. This is the first
      demonstration of a chimera between these two unrelated receptor families that
      responds to ligand stimulation. The results indicate that the mechanisms by which
      receptor tyrosine kinases and cytokine receptors propagate mitogenic signals are
      sufficiently similar to allow interchange of their ligand binding domains and
      that generation of an efficient mitogenic signal by a cytokine receptor depends
      primarily on its cytoplasmic and/or transmembrane regions.

PMID- 8294398
TI  - Cloning and expression of a membrane receptor for secretory phospholipases A2.
AB  - Snake venom and mammalian secretory phospholipases A2 are structurally related
      enzymes that have been associated with several toxic (neurotoxicity, myotoxicity,
      etc.), pathological (inflammation, hypersensitivity, etc.), or physiological
      (contraction, proliferation, etc.) processes. We have previously shown that snake
      venom PLA2s have specific high affinity receptors. Here, we report the molecular
      cloning of one of these PLA2 receptors (molecular mass approximately 180 kDa),
      previously purified from rabbit skeletal muscle. It is a membrane protein with a
      N-terminal cysteine-rich domain, a fibronectin type II domain, eight repeats of a
      carbohydrate recognition domain, a unique transmembrane domain, and a
      intracellular C-terminal domain. The 1458-residue PLA2 receptor, expressed in
      transfected cells, binds svPLA2 with very high affinities (Kd values
      approximately 10-20 pM). It also tightly binds the two structural types of
      msPLA2s, i.e. pancreatic PLA2 and synovial PLA2 (Kd approximately 1-10 nM). This
      receptor might have a key role in normal and pathological actions of secretory
      PLA2s.

PMID- 8294399
TI  - The cytoplasmic domain of the interleukin-1 receptor is required for nuclear
      factor-kappa B signal transduction.
AB  - Interleukin-1 (IL-1) plays a central role in mediating immune and inflammatory
      responses. Binding of IL-1 to the type I 80-kDa receptor results in generation of
      intracellular signals and activation of the transcription factor NF-kappa B.
      However, the nature of the signals required to generate NF-kappa B binding
      activity remains unclear. In this paper, we show that NF-kappa B1 (p50) and RelA
      (p65) were specifically translocated to the nucleus following activation of
      intact type I IL-1 receptor (IL-1R). The C-terminal region of the type I IL-1R is
      required for this effect, and deletion of its cytoplasmic domain abrogates the
      activation of NF-kappa B by IL-1. These results provide evidence that IL-1
      modulates the activity of NF-kappa B through the type I IL-1 receptor and
      identifies a domain required for signal transduction to this specific
      transcription factor.

PMID- 8294400
TI  - Biologically active two-dimensional crystals of aquaporin CHIP.
AB  - Plasma membranes of several mammalian tissues are highly permeable to water due
      to the presence of CHIP, the 28-kDa channel-forming integral protein which is the
      archetypal member of the aquaporin family of water channel proteins. To define
      its native structure, purified red cell CHIP protein was reconstituted into lipid
      bilayers at a high protein-to-lipid ratio, and the resulting 3-microns diameter
      membrane vesicles were examined by high resolution electron microscopy. The
      reconstituted membranes contained highly ordered two-dimensional crystalline
      lattices of p422(1) symmetry in which each CHIP tetramer contained a central
      depression extending from the outer and inner surfaces of the membrane into the
      transbilayer domain of the molecule. The reconstituted membranes also exhibited
      extremely high osmotic water permeability, Pf = 0.472 cm/s, corresponding to the
      sum of activities of all incorporated CHIP molecules. These studies report the
      first two-dimensional crystallization of a biologically active water channel and
      provide direct evidence of the structure responsible for its pore-like behavior.

PMID- 8294401
TI  - Unprocessed myogenin transcripts accumulate during mouse embryogenesis.
AB  - The gene myogenin encodes a helix-loop-helix protein whose function is critical
      to the integrity of the mammalian myogenic cascade. In vitro, the expression of
      this gene immediately precedes terminal differentiation, as measured by the
      synthesis of those proteins that make up the contractile apparatus. However,
      during mammalian development, expression of myogenin and the appearance of
      sarcomeres are separated by at least 1 week. The observation that early embryos
      (10.5 days post coitum) do not possess myogenin protein despite the fact that
      transcripts are detected (Cusella-De Angelis et al. (1992) J. Cell Biol. 116,
      1243-1255), suggests the possibility of post-transcriptional regulation. Using
      polymerase chain reaction and in situ analyses, we report here that the mouse
      embryo accumulates a significant pool of unprocessed myogenin RNA in the
      developing somites (10.5 days post coitum). These results indicate that post
      transcriptional regulation of myogenin may occur at the RNA processing level.

PMID- 8294402
TI  - Positive and negative regulation of retinoid X receptor gene expression by
      thyroid hormone in the rat. Transcriptional and post-transcriptional controls by
      thyroid hormone.
AB  - The 9-cis-retinoic acid receptors (RXRs), belonging to the members of the
      steroid/thyroid hormone receptor superfamily, act as auxiliary proteins,
      heterodimerizing with other nuclear receptors such as retinoic acid receptors
      (RARs), vitamin D receptor, thyroid hormone receptors, and peroxisome
      proliferator activated receptor, thereby transactivating target genes in a ligand
      dependent manner. We have previously reported that in the rat, thyroid hormone
      (TH) positively and negatively regulates the hepatic mRNA levels of RXR beta and
      RXR gamma, respectively. In the present study, we have tried to elucidate the
      level at which TH regulates the gene expression of RXR beta and RXR gamma in the
      rat. A RNA synthesis inhibitor (actinomycin D), but not a protein synthesis
      inhibitor (cycloheximide), blocked the induction of RXR beta mRNA by TH. On the
      other hand, none of these drugs inhibited the decrease of RXR gamma mRNA levels
      caused by TH. Nuclear run-on assays showed that the transcription rate of the RXR
      beta gene was positively regulated by TH, whereas the transcription of RXR gamma
      gene was not controlled by TH. Taken together, these results indicate that the
      gene expression of RXR beta is positively regulated by TH at transcriptional
      level, while the negative regulation of the RXR gamma gene expression by TH may
      occur at a post-transcriptional level in intact rat. Thus, the RXR-mediated
      signal transductions may be modulated in part through TH control of the levels of
      RXR beta and RXR gamma.

PMID- 8294403
TI  - The adapter protein Shc interacts with the interleukin-2 (IL-2) receptor upon IL
      2 stimulation.
AB  - Binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) stimulates Src
      family kinases, tyrosine phosphorylation of several proteins, conversion of Ras
      to its active GTP-bound form, and eventually c-fos, c-jun, and c-myc induction.
      The IL-2R beta chain plays a crucial role in IL-2R signaling. Within the
      cytoplasmic domain of the beta chain, a region essential for mitogenesis and
      another involved in binding the Src family kinase Lck have been defined. The beta
      chain itself is tyrosine-phosphorylated upon IL-2 stimulation. Since the adapter
      protein Shc acts upstream of Ras and is involved in T cell receptor-mediated Ras
      activation, we examined the role of Shc in IL-2 signaling. Shc was found to be
      tyrosine-phosphorylated upon IL-2 stimulation in CTLL-20 cells. After its
      phosphorylation, Shc interacted with another adapter protein, Grb2, and, via
      Grb2, with the Ras GTP/GDP exchange factor mSOS. After IL-2 stimulation, Shc also
      associated with the IL-2R beta chain. Thus, during IL-2 signaling, the
      interaction of Shc with the IL-2R beta chain and its simultaneous association
      with Grb2 and mSOS may couple IL-2R stimulation to Ras signaling.

PMID- 8294404
TI  - Heterologous expression of a cardiomyopathic myosin that is defective in its
      actin interaction.
AB  - A point mutation in the heavy chain of cardiac myosin, resulting in replacement
      of an arginine (Arg) with glutamine (Gln), has been linked to hypertrophic
      cardiomyopathy in humans (Geisterfer-Lowrance, A. A. T., Kass, S., Tanigawa, G.,
      Vosberg, H.-P., McKenna, W., Seidman, J. G., and Seidman, C. E. (1990) Cell 62,
      999-1006). To determine the functional impact of this mutation, baculovirus
      driven coexpression of myosin heavy and light chains has been developed. The Arg
      403-->Gln mutation resulted in cardiac myosin with normal ATPase activity in the
      absence of actin. However, in the presence of actin, ATPase activity was greatly
      reduced (Vmax decreased > 3.5-fold and K(app) increased > 3-fold). In vitro
      motility was reduced nearly 5-fold by this single amino acid mutation. Thus, Arg
      403 likely contributes to an important interaction at the actin interface of
      myosin. Replacement of Arg-403 with Gln leads to decreased rate(s) of transition
      within the actin-myosin crossbridge cycle. In humans, this mutation will result
      in decreased power output per unit area of cardiac muscle, likely providing a
      stimulus for hypertrophy.

PMID- 8294405
TI  - Glutathione peroxidase compensates for the hypersensitivity of Cu,Zn-superoxide
      dismutase overproducers to oxidant stress.
AB  - The balance between several components of the antioxidant defenses appears to be
      important for the cellular resistance to oxidative stress. While Cu,Zn-superoxide
      dismutase (SOD) transfectants of mouse epidermal cells JB6 clone 41 were
      sensitized to oxidants produced by xanthine/xanthine oxidase (X/XO) consecutive
      transfection with catalase corrected their hypersensitivity (Amstad, P., Peskin,
      A., Shah, G., Mirault, M. E., Moret, R., Zbinden, I., and Cerutti, P. (1991)
      Biochemistry 30, 9305-9313). We studied the effect of the transfection of bovine
      selenoglutathione peroxidase (GPx) on the sensitivity of JB6 clone 41 and its SOD
      transfectants. Sensitivity to DNA strand breakage and killing by X/XO was
      reversely related to the activity ratios GPx over SOD. A GPx-transfectant of JB6
      clone 41 cells with a GPx/SOD ratio of 3.8 was very strongly protected. The
      hypersensitivity of the SOD clones with GPx/SOD ratios of 0.4 was corrected or
      overcorrected by secondary transfection with bovine Se-GPx resulting in increased
      activity ratios GPx/SOD of 1 to 2.4. Our results indicate that small deviations
      from the physiological activity ratios of GPx/SOD have a dramatic effect on the
      resistance of cells to oxidant-induced damage to the genome and cell killing.

PMID- 8294406
TI  - Hydrogen bonding interaction of thyrotropin-releasing hormone (TRH) with
      transmembrane tyrosine 106 of the TRH receptor.
AB  - Thyrotropin-releasing hormone (TRH, pyroglutamic acid-histidine-proline-amide)
      binds to a seven-transmembrane-spanning, G protein-coupled receptor. We tested
      the hypothesis that Tyr106 of the third transmembrane helix of the TRH receptor
      (TRH-R) binds pyroglutamyl of TRH by mutating Tyr106 to Phe and replacing the
      ring carbonyl of the TRH pyroglutamyl moiety with a methylene group ([Pro1]TRH).
      Compared to the affinity of wild-type TRH-R for TRH, the affinities of
      [Phe106]TRH-R for TRH and of wild-type TRH-R for [Pro1]TRH were 100,000- and
      110,000-fold lower, respectively. The affinity of [Phe106]TRH-R for [Pro1]TRH was
      only 16-fold lower than that for TRH, demonstrating a lack of additivity of the
      effects of these changes in the receptor and ligand. These data provide
      compelling evidence that the hydroxyl group of Tyr106 of the TRH-R binds the TRH
      pyroglutamyl carbonyl group. To our knowledge, this represents the highest
      affinity, non-covalent bond yet observed between single functional groups of a
      GPCR and ligand and is the first delineation of a direct binding interaction
      between a residue in the transmembrane core of a GPCR and a specific moiety of a
      peptide agonist.

PMID- 8294407
TI  - Proteolysis of SNAP-25 by types E and A botulinal neurotoxins.
AB  - Clostridial neurotoxins, tetanus toxin (TeTx) and the seven related but
      serologically distinct botulinal neurotoxins (BoNT/A to BoNT/G), are potent
      inhibitors of synaptic vesicle exocytosis in nerve endings. Recently it was
      reported that the light chains of clostridial neurotoxins act as zinc-dependent
      metalloproteases which specifically cleave synaptic target proteins such as
      synaptobrevin/VAMPs, HPC-1/syntaxin (BoNT/C1), and SNAP-25 (BoNT/A). We show here
      that BoNT/E, like BoNT/A, cleaves SNAP-25, as generated by in vitro translation
      or by expression in Escherichia coli. BoNT/E cleaves the Arg180-Ile181 bond. This
      site is different from that of BoNT/A, which cleaves SNAP-25 between the amino
      acid residues Gln197 and Arg198. These findings further support the view that
      clostridial neurotoxins have evolved from an ancestral protease recognizing the
      exocytotic fusion machinery of synaptic vesicles whereby individual toxins target
      different members of the membrane fusion complex.

PMID- 8294408
TI  - On the protective mechanism of the thiol-specific antioxidant enzyme against the
      oxidative damage of biomacromolecules.
AB  - A thiol-specific antioxidant enzyme (TSA), which provides protection against the
      inactivation of other enzymes by the thiol/Fe(III)/oxygen system, was previously
      isolated and cloned. We investigated the mechanism by which TSA protects
      biomolecules from oxidative damage caused by the thiol-containing oxidation
      system using the spin trapping method with 5,5-dimethyl-1-pyrroline N-oxide
      (DMPO). Thiyl radicals from dithiothreitol (.DTT) were produced by horseradish
      peroxidase/H2O2 under aerobic and anaerobic conditions and by the Fe(III)/oxygen
      system. The formation of DMPO-.DTT radical adducts were inhibited by TSA
      regardless of the thiyl radical-generating conditions used. The active mutant
      C170S also quenched the signals of the radical adduct, whereas the inactive
      mutant C47S did not exert any effect. It was also found that C170S has a higher
      rate at the initial stage of the reaction than that of the native enzyme,
      although C170S failed to remove DMPO-.DTT radical adducts completely. These
      results indicate that only active TSA can catalyze the removal of thiyl radicals,
      and cysteine 47 is required for this activity. In addition, thiyl radicals react
      with oxygen to generate unidentified thiylperoxy species. Fe.EDTA reacts with
      this species to generate a reactive radical that can abstract hydrogen atom from
      ethanol to produce a hydroxyethyl radical. This reactive thiyl-oxygen radical is
      believed to be responsible for causing deleterious effects on biomolecules.
      Together, our data indicate that TSA protects biomolecules from oxidative damage
      by catalyzing the removal of thiyl radicals before they generate more reactive
      radicals. However, presently we cannot rule out the possibility that TSA can also
      use other thiol-containing species as substrates.

PMID- 8294409
TI  - Extended junctional sarcoplasmic reticulum of avian cardiac muscle contains
      functional ryanodine receptors.
AB  - The ryanodine receptor (RYR)/Ca2+ release channel of avian cardiac muscle was
      localized by immunocytochemical techniques and biochemically characterized using
      isolated membrane and receptor protein fractions. Monoclonal antibody C3-33
      raised against the canine cardiac RYR bound to the junctional sarcoplasmic
      reticulum of pigeon and finch hearts, both at peripheral couplings and at
      extended junctional sarcoplasmic reticulum (EJSR). Immunoblots of sarcoplasmic
      reticulum vesicles from pigeon and finch hearts showed this antibody recognized a
      single high molecular weight protein, which co-migrated with the canine M(r)
      565,000 RYR/Ca2+ release channel polypeptide. The pigeon heart RYR bound
      [3H]ryanodine with high affinity in a Ca(2+)-dependent manner, comparable to the
      canine cardiac RYR. Purification of the pigeon RYR yielded a 30 S protein
      complex, which bound the maximum calculated amount of [3H]ryanodine ((440 +/- 60)
      pmol/mg protein), assuming one high affinity site/tetrameric 30 S RYR comprised
      of M(r) 565,000 polypeptides. Autoradiography of isolated finch cardiac myocytes
      indicated [3H]ryanodine binding throughout the cells. These results suggest that
      avian heart contains a single population of RYRs, and thereby support the
      hypothesis that avian EJSR contains functional calcium release channels which,
      because of the absence of transverse tubules, can be located micrometers away
      from the surface membrane in avian heart.

PMID- 8294410
TI  - A structure/activity study of calcium affinity and selectivity using a synthetic
      peptide model of the helix-loop-helix calcium-binding motif.
AB  - The acid pair hypothesis predicts the calcium affinity of the helix-loop-helix
      calcium-binding motif based on the number and location of acidic amino acid
      residues in chelating positions of the calcium-binding loop region. This study
      investigates the effects of the number and position of acidic residues in the
      loop region on calcium affinity and selectivity using 33-residue synthetic models
      of single helix-loop-helix calcium-binding motifs. Increasing the number of
      acidic residues in the octahedrally arranged chelating positions of the loop
      region from 3 to 4 by replacing an asparagine in the +y position with an aspartic
      acid increases the calcium affinity of the models between 2- and 38-fold.
      Differences in affinities are more pronounced in the models containing an x axis
      acid pair. The calcium affinities of peptide models containing 3 or 4 acidic
      residues in chelating positions of the loop region and an x axis acid pair are
      reduced when the residue in the +z position is changed from asparagine to serine.
      A similar reduction in calcium affinity occurs in the z axis acid paired peptides
      when the -x chelating residue is changed from serine to asparagine. Models with 3
      acidic residues in chelating positions containing a z axis acid pair have greater
      calcium affinity than comparable peptide models with an x axis acid pair. The
      presence of x or z axis acid pairs in comparable peptides containing 4 acidic
      residues in chelating positions does not greatly alter calcium affinity. Calcium
      selectivity resides in x axis acid paired peptides, whereas z axis acid paired
      peptides exhibit both magnesium- and calcium-induced structural changes. This ion
      selectivity may be explained by postulating that the z axis residue side chains
      produce the initial, rate-limiting interactions with the cation, causing
      hydration shell destabilization and initiating the subsequent ligand
      interactions.

PMID- 8294411
TI  - Two distinct regions of the LamB signal sequence function in different steps in
      export.
AB  - The hydrophobic core of the Escherichia coli LamB signal sequence contains two
      structurally distinct regions. One region forms a helix in nonpolar environments,
      and the other is less structured. These regions seem to be of special importance
      for export, as judged by the magnitude of the defect caused by their mutational
      inactivation. To gain insight into the mechanistic importance of these two
      regions, we examined the ability of precursors to pass partially through the
      export pathway when each region is mutated. The results demonstrate that
      mutations in the helical and unstructured regions of the signal sequence block
      different steps in the export pathway.

PMID- 8294412
TI  - Tubulointerstitial nephritis antigen interacts with laminin and type IV collagen
      and promotes cell adhesion.
AB  - Tubulointerstitial nephritis (TIN) antigen has been recently identified as a
      novel basement membrane macromolecule. It consists of a single chain of 58 kDa
      and exhibits a restricted distribution. The interaction between TIN antigen and
      laminin or type IV collagen has been studied using solid-phase binding assays and
      found to be for both macromolecules specific, saturable, and with an affinity in
      the low micromolar range. In similar assays, TIN antigen did not interact with
      heparin. In turbidimetry assays, it was found that the presence of TIN antigen
      did not affect the polymerization of type IV collagen but had a concentration
      dependent inhibitory effect on laminin polymerization and on preformed laminin
      polymers. TIN antigen was able to promote adhesion of epithelial cells derived
      from kidney tubules and of endothelial cells derived from aorta. The data suggest
      that TIN antigen may be a macromolecule of importance both for basement membrane
      ultrastructure and cellular adhesion.

PMID- 8294413
TI  - The interaction of calmodulin with regulatory peptides of phosphorylase kinase.
AB  - The regulatory peptides Phk13 (301-327) and Phk5 (342-367) have been synthesized
      and their interaction with calmodulin studied. In the case of Phk13 modified
      forms were also synthesized in which a tryptophan group was placed at position 4
      or 21, as well as a form with tryptophan at position 4 and nitrotyrosine at
      position 21. From tryptic digestion, circular dichroism, and radiationless energy
      transfer measurements, it appears that Phk13 forms an elongated complex with
      calmodulin in which the peptide is in a non-helical conformation, probably bent
      into a hairpin-shaped structure, the connecting strand of calmodulin is extended
      and exposed to the action of proteolytic enzymes, and the peptide makes contact
      with both the N- and C-terminal half-molecules of calmodulin. In contrast, the
      Phk5 peptide has an alpha-helical conformation in the complex, which is
      relatively compact in shape.

PMID- 8294414
TI  - Differential formation and repair of the mutagenic DNA alkylation product O6
      ethylguanine in transcribed and nontranscribed genes of the rat.
AB  - Intragenomic differences regarding the formation and repair of carcinogen-DNA
      adducts influence gene-specific mutational patterns and the cellular risk of
      malignant conversion. Using a newly developed, monoclonal antibody-based
      immunoaffinity method (Hochleitner, K., Thomale, J., Nikitin, A. Y., and
      Rajewsky, M. F. (1991) Nucleic Acids Res. 19, 4467-4472), it has become possible
      to quantitate the mutagenic DNA alkylation product O6-ethylguanine (O6-EtGua) at
      the level of single-copy genes. We have analyzed the formation and repair
      kinetics of O6-EtGua in DNA in relation to the transcriptional activity of
      selected genes in two isogenic rat hepatoma cell lines (Fao and H5) exposed to N
      ethyl-N-nitrosourea. Whereas the frequency of O6-EtGua initially formed in the
      inactive immunoglobulin E gene was indistinguishable from the value for bulk DNA,
      the initial O6-EtGua/guanine molar ratio in the transcribed beta-actin gene was
      nearly three times higher. The overall elimination rates of O6-EtGua were the
      same for bulk DNA and the IgE gene sequence, i.e. rapid in Fao cells (68% removed
      within 20 min) and four times slower in H5 cells. Preferential repair was found
      in the transcribed gene: during the initial phase of elimination, the half-life
      of O6-EtGua in the beta-actin gene was three times shorter than in the IgE gene
      in Fao cells (5 versus 15 min) and 12 times shorter in H5 cells (20 min versus 4
      h).

PMID- 8294415
TI  - Regulatory region of plasma membrane Ca2+ pump. 28 residues suffice to bind
      calmodulin but more are needed for full auto-inhibition of the activity.
AB  - The Ca(2+)-pumping activity of constructs containing various portions of the
      putative 28-residue calmodulin-binding domain (C domain) of hPMCA4b were
      compared. As the length of the C domain in the pump increased, the pump's
      activity decreased and the ability of calmodulin to stimulate the activity
      increased. Study of the calmodulin dependence of activity showed that the
      construct containing all 28 residues of the C domain had a K1/2 for calmodulin
      equal to that of the complete molecule; the constructs containing less of the C
      domain interacted less strongly with calmodulin. On the other hand, incorporation
      of all 28 residues of the C domain did not decrease the activity of the pump (in
      the absence of calmodulin) as low as the activity of the complete molecule. This
      indicates that other segments of the molecule, further toward the COOH terminus,
      are also required for the degree of inhibition seen in the complete molecule.

PMID- 8294416
TI  - trp repressor mutations alter DNA complex stoichiometry.
AB  - We have examined the interaction of a series of mutant trp repressors with
      various operator DNA sequences using gel retardation. Binding to 40 base pairs
      (bp) TrpEDCBA operator yielded patterns distinct from the wild-type protein for
      superrepressors EK13, EK18, and EK49, with a protein-DNA complex of higher
      stoichiometry (three dimers/operator) than observed for wild-type repressor (two
      dimers/operator). This higher stoichiometry complex may contribute to the
      enhanced binding affinity and higher protein-operator stability observed for the
      superrepressors. In contrast, DN46 displayed the same complexes characteristic of
      the wild-type protein, although the complex of a single dimer with operator was
      more prominent in the DN46 binding pattern than wild-type despite higher apparent
      affinity of this protein for TrpEDCBA operator than wild-type protein. The
      binding of AV77 was indistinguishable from the wild-type protein. Similar
      patterns to that found for TrpEDCBA were also observed for the 40-bp aroH
      operator and symmetrized derivatives of TrpEDCBA for these superrepressors.
      Binding of EK13, EK18, and EK49 superrepressors to half-site DNAs, composed of 20
      bp of TrpEDCBA sequence coupled with 20 bp of lac operator sequence, yielded 2:1
      complex as the primary product with no detectable 3:1 complex; thus, two half
      sites appear to be required for generation of the 3:1 complex. Mutation in the
      tryptophan-binding site can also generate higher order complexes with TrpEDCBA
      DNA as demonstrated by the binding of VA58; the presence of 3:1 complex with this
      protein was also dependent on the presence of two half-sites. In addition to
      effects of sequence changes in the protein, the ligand employed can influence the
      binding pattern, as demonstrated for EK49 and VA58 using 5-methyl-tryptophan; the
      3:1 complex is produced more prominently and at lower protein concentration for
      both mutants. It is apparent from these data that binding of the trp repressor to
      DNA is influenced by the operator sequence, the nature of the corepressor, as
      well as interactions (perhaps involving the N-terminal regions) that occur within
      and between the dimeric structure of this protein.

PMID- 8294417
TI  - NMR studies of peptides derived from the putative binding regions of cartilage
      proteins. No evidence for binding to hyaluronan.
AB  - Previous work has implicated sequences within the tandem repeats of cartilage
      link protein in the interaction of link protein with hyaluronan. This conclusion
      was based on competitive inhibition experiments using synthetic peptides
      (Goetinck, P. F., Stirpe, N. S., Tsonis, P. A., and Carlone, D. (1987) J. Cell
      Biol. 105, 2403-2407). Further investigation of this system using high resolution
      nuclear magnetic resonance, circular dichroism, and competitive inhibition with
      other peptides indicates that the previously observed inhibition of link protein
      hyaluronan binding was not caused by peptide-hyaluronan interactions. Instead,
      nonspecific aggregation of the peptides with link protein is proposed to account
      for all of the experimental data. Consequently, there is no direct experimental
      evidence to support the conclusion that these sequences in the tandem repeats of
      link protein are responsible for the link protein-hyaluronan interaction. If
      these peptides do represent the hyaluronan binding regions of link protein, these
      results imply a highly structure-dependent interaction between link protein and
      hyaluronan. Conformational analysis of the peptides using two-dimensional nuclear
      Overhauser spectroscopy indicates that the linear peptides do not adopt any
      stable secondary structure. However, several residues in the disulfide-looped
      peptides exhibit connectivities, suggesting a relatively long-lived extended
      chain conformation, consistent with predictions of secondary structure based on
      sequence analysis.

PMID- 8294418
TI  - Phorbol esters and norepinephrine destabilize alpha 1B-adrenergic receptor mRNA
      in vascular smooth muscle cells.
AB  - The mechanism by which norepinephrine (NE) down-regulates alpha 1B-adrenergic
      receptor (alpha-AR) mRNA was studied in rabbit aortic smooth muscle cells. NE,
      phorbol esters, and bradykinin each decreased alpha-AR mRNA levels by 70-80%. The
      protein kinase C inhibitor (+)-1-(5-isoquinolinesulfonyl)-2-methylpiperazine
      dihydrochloride (H-7) abolished the effects of phorbol esters and NE and
      decreased basal mRNA levels by 52 +/- 3%. Neither ryanodine nor EGTA inhibited
      down-regulation of alpha-AR mRNA by NE. Actinomycin D caused alpha-AR mRNA level
      to decrease with a half-life of 3.2 +/- 0.4 h and blocked the effect of H-7 to
      decrease basal alpha-AR mRNA level. Both NE and phorbol esters increased the rate
      of alpha-AR mRNA degradation. In NE-desensitized cells, phorbol esters and
      bradykinin each caused the expected down-regulation of alpha-AR mRNA. The protein
      phosphatase inhibitor okadaic acid prolonged the normally transient effect of NE
      for at least 24 h. We conclude that protein kinase C exerts two opposing effects
      on alpha-AR mRNA levels, 1) a decrease in the stability of the mRNA that requires
      the sustained phosphorylation of a protein kinase C substrate and 2) a permissive
      effect on alpha-AR gene transcription.

PMID- 8294419
TI  - Mispair-, site-, and strand-specific error rates during simian virus 40 origin
      dependent replication in vitro with excess deoxythymidine triphosphate.
AB  - We have measured the fidelity of leading and lagging strand DNA replication in
      HeLa cell extracts. Providing an excess of one dNTP in reactions induces
      replication errors consistent with misincorporation of that dNTP. With excess
      dTTP, both substitutions and single-nucleotide frameshifts are induced. Error
      distribution is nonrandom; reproducible hot spots for a substitution and a
      frameshift error are observed. Measurements with two vectors having the origin of
      replication on opposite sides of the mutational target demonstrate that error
      rates for G.dTTP and C.dTTP mispairs depend on whether the strand is replicated
      as the leading or lagging strand. Also, the two hot spots are only observed in
      one origin-target orientation. Replication reactions reconstituted from two
      fractions derived from extracts are 3-fold less accurate, but the error
      specificity with excess dTTP is similar to that with extracts. This suggests that
      the processes responsible for the nonrandom error rates are not lost as a result
      of fractionation. Furthermore, the reconstituted system is devoid of mismatch
      repair activity. Thus, mismatch repair is not responsible for the mispair-, site
      , and strand-specific differences observed.

PMID- 8294420
TI  - Purification and kinetic parameters of bovine liver N-acetylglucosamine-1
      phosphodiester alpha-N-acetylglucosaminidase.
AB  - The enzyme N-acetylglucosamine phosphodiester alpha-N-acetylglucosaminidase
      (phosphodiester alpha-GlcNAcase) catalyzes the second step in the formation of
      the mannose 6-phosphate targeting signal on lysosomal enzyme oligosaccharides by
      removing GlcNAc residues from GlcNAc-alpha-P-mannose moieties, which are formed
      in the first step by UDP-N-acetyl-glucosamine:glycoprotein N-acetylglucosamine-1
      phosphotransferase (GlcNAc-phosphotransferase). Phosphodiester alpha-GlcNAcase, a
      membrane-bound enzyme, has been purified about 3,000-fold from bovine liver to
      apparent homogeneity using detergent solubilization, fractionation on DEAE
      cellulose, affinity chromatography on lectin-Sepharose columns, gel filtration,
      and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme
      migrated as 129- and 121-kDa species on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Since both bands had the same amino-terminal sequence, the
      smaller species is presumed to be derived from the larger by proteolysis. Kinetic
      analysis of bovine phosphodiester alpha-GlcNAcase with enzymatically synthesized
      artificial and biological substrates indicates that phosphodiester alpha
      GlcNAcase requires GlcNAc-alpha-P R for substrate and that when R contains the
      Man alpha 1,2Man linkage the substrate binding is most effective. Unlike GlcNAc
      phosphotransferase, bovine phosphodiester alpha-GlcNAcase does not require a
      protein recognition determinant on lysosomal enzyme substrates.

PMID- 8294421
TI  - Characterization and immunolocalization of bovine N-acetylglucosamine-1
      phosphodiester alpha-N-acetylglucosaminidase.
AB  - N-Acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase
      (phosphodiester alpha-GlcNAcase) has been purified 3,000-fold from bovine liver
      and its kinetic properties determined as described in the previous report
      (Mullis, K. G., Huynh, M., and Kornfeld, R. (1993) J. Biol. Chem. 269, 1718
      1726). This report describes the hydrodynamic and lectin binding properties of
      phosphodiester alpha-GlcNAcase as well as its intracellular localization. The
      molecular weight of phosphodiester alpha-GlcNAcase is 204,950, as determined from
      density gradient centrifugation in D2O and H2O glycerol gradients and gel
      filtration. Enzymatically active enzyme migrates on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis with a molecular weight of 129,000, consistent
      with native phosphodiester alpha-GlcNAcase being a dimer. The lectin binding
      properties of phosphodiester alpha-GlcNAcase indicate that it contains sialylated
      species of both complex type N-linked oligosaccharides and O-linked
      oligosaccharides. In immunofluorescence studies phosphodiester alpha-GlcNAcase
      shows a perinuclear, Golgi localization in Vero cells as does the mid-Golgi
      marker alpha-mannosidase II. After exposure of the Vero cells to brefeldin A,
      phosphodiester alpha-GlcNAcase assumes an endoplasmic reticulum staining pattern.
      In contrast, in cells costained with the trans-Golgi marker wheat germ
      agglutinin, the wheat germ agglutinin marker assumed an endosomal network
      appearance after exposure to brefeldin A. These findings indicate that
      phosphodiester alpha-GlcNAcase is normally located within the Golgi stack,
      separate from the trans-Golgi and trans-Golgi network stained by wheat germ
      agglutinin.

PMID- 8294422
TI  - Kinetic heterogeneity of phosphoenzyme of Na,K-ATPase modeled by unmixed lipid
      phases. Competence of the phosphointermediate.
AB  - Interconversion of phosphoenzyme resistant to K+ and sensitive to ADP (E1P) and
      phosphoenzyme resistant to ADP and sensitive to K+ (E2P) was studied in bovine
      brain and dog and pig kidney. The kinetics of dephosphorylation were observed by
      chasing phosphoenzyme formed from [32P]ATP with unlabeled ATP with or without ADP
      or K+. Phosphorylation in 0.6-1.0 M NaCl produced mostly ADP-sensitive potassium
      insensitive E1P. A potassium chase of this phosphoenzyme exposed its rate of
      conversion to potassium-sensitive ADP-insensitive E2P. At 20 degrees C the rate
      constant was approximately 1 s-1. Simultaneous dilution of [NaCl] in the chase to
      100 mM increased the constant to approximately 60 s-1, which probably qualifies
      E1P as an intermediate in Na,K-ATPase activity. Anions inhibited conversion
      according to a Hofmeister series. Na+ had no specific effect. At 0 degrees C the
      rate constant was < 0.4 s-1, but downward jumps in [salt] produced an
      acceleration to > 1 s-1 for < 3 s followed by a return to the slow rate. The
      rapid rate would qualify E1P to participate in Na,K-ATPase activity if this rapid
      state participates in the normal reaction cycle. Phosphorylation in 0.02-0.1 M
      NaCl produced mostly E2P. Upward jumps in [NaCl] converted E2P to E1P equally
      rapidly and transiently. Oligomycin and high [salt] cooperated in stabilizing
      E1P. Jumps in [salt] greatly and transiently increased the rate of conversion of
      one form of the phosphoenzyme to the other. This extraordinary result required
      heterogeneous kinetics. A model is proposed based on control of enzyme
      conformation by changes in separate unmixed phases of the lipid of the membrane.

PMID- 8294423
TI  - A set of endoplasmic reticulum proteins possessing properties of molecular
      chaperones includes Ca(2+)-binding proteins and members of the thioredoxin
      superfamily.
AB  - The major proteins in the lumen of the endoplasmic reticulum (ER) are thought to
      function in Ca2+ sequestration or as "molecular chaperones" in the folding and
      assembly of membrane or secreted proteins. Based on the ability of many
      chaperones to bind selectively to unfolded proteins and to dissociate from them
      upon ATP hydrolysis, we developed an affinity chromatography method to isolate
      proteins with these characteristics from pancreatic or liver ER. Seven ER
      proteins bound selectively to denatured protein columns and were specifically
      eluted by ATP (10(-6) M) but not by a nonhydrolyzable ATP analog. These proteins
      were identified with antibodies and microsequencing as the ER chaperone BiP
      (grp78), grp94, calreticulin, a novel 46-kDa protein that binds azido-ATP, as
      well as three members of the thioredoxin superfamily: protein-disulfide
      isomerase, ERp72, and a previously reported 50-kDa protein (p50). This set of
      seven proteins bound to and was eluted with ATP from a variety of denatured
      proteins, including histone, gelatin, alpha fetoprotein, thyroglobulin, lysozyme,
      casein, and IgG. The release of grp94, protein-disulfide isomerase, ERp72,
      calreticulin, and p50 was stimulated by Ca2+ in the presence of ATP. These
      proteins thus appear to function as Ca(2+)-dependent chaperones, which may
      account for the Ca2+ and ATP requirement for protein folding in the ER.

PMID- 8294424
TI  - Generation of a truncated hepatocyte growth factor receptor in the endoplasmic
      reticulum.
AB  - The hepatocyte growth factor (HGF) receptor (p190MET) is a tyrosine kinase
      composed of two disulfide-linked chains, alpha of 50 kDa and beta of 145 kDa. We
      have previously described an isoform (p140MET) containing a beta chain of 85 kDa,
      lacking the cytoplasmic kinase domain. The two receptor variants originate by
      post-translational processing of a common single-chain precursor of 170 kDa
      (Pr170). In the endoplasmic reticulum a fraction of Pr170 is cleaved at the
      cytosolic side generating an intermediate product of 120 kDa (Pr120). This
      molecule 1) is already detectable after 15 min of pulse labeling, 2) contains
      high mannose-branched oligosaccharides, and 3) accumulates upon treatments
      inhibiting the export from the endoplasmic reticulum. A second cleavage,
      occurring after 30 min of chase in the trans-Golgi network, converts the single
      chain precursors Pr170 and Pr120 into the mature heterodimers p190MET and
      p140MET. This process is inhibited by brefeldin A treatment. Conditions leading
      to Pr170 accumulation in the endoplasmic reticulum, such as receptor
      overexpression, induce kinase activation and overproduction of Pr120. Conversely,
      cells expressing a kinase-defective HGF receptor lack the truncated isoform. The
      proteolytic cleavage of the cytoplasmic domain may thus represent a safety
      mechanism aimed at preventing ligand-independent intracellular activation of the
      HGF receptor kinase.

PMID- 8294425
TI  - Conversion of diacylglycerol to phosphatidylcholine on the basolateral surface of
      epithelial (Madin-Darby canine kidney) cells. Evidence for the reverse action of
      a sphingomyelin synthase.
AB  - When N-6[7-nitro-2,1,3-benzoxadiazol-4-yl]aminohexanoyl-phosphatidic acid (C6-NBD
      PA) is inserted into the plasma membrane of fibroblasts, it is metabolized by the
      cells to C6-NBD-diacylglycerol (DG), -triacylglycerol, -phosphatidylcholine (PC),
      and -phosphatidylethanolamine (PE) (Pagano, R. E., Longmuir, K. J., and Martin,
      O. C. (1983) J. Biol. Chem. 258, 2034-2040). In Madin-Darby canine kidney (MDCK)
      cells incubated at 10 degrees C with C6-NBD-PA, up to 70% of the newly
      synthesized C6-NBD-PC but no C6-NBD-PE could be depleted from the basolateral
      cell surface by the addition of bovine serum albumin to the medium. Preincubation
      of the cells with [3H]choline for 2 h at 37 degrees C prior to C6-NBD-PA addition
      at 10 degrees C labeled non-depletable C6-NBD-PC with a specific activity of > 10
      times that of the depletable C6-NBD-PC on the basolateral cell surface,
      indicating that the latter had not been synthesized by the CDP-choline pathway.
      C6-NBD-DG could substitute for C6-NBD-PA as substrate for both intracellular and
      surface C6-NBD-PC synthesis. In addition, C6-NBD-PC synthesis on the cell surface
      was independent of the location of the C6-NBD-chain on the 1- or 2-position,
      indicating that the reaction occurred by transfer of phosphorylcholine. Using C6
      NBD-ceramide, C6-NBD-sphingomyelin (SM) synthesis also was discovered on the
      basolateral but not on the apical cell surface. The conversion of PC plus
      ceramide to DG and SM on the basolateral MDCK cell surface suggests that the
      synthesis of C6-NBD-PC on this surface occurred via the reverse reaction of a SM
      synthase. Indeed, the surface C6-NBD-PC synthesis was reduced to 40-50% by
      addition of C6-NBD-ceramide or hydrolysis of cell surface SM by exogenous neutral
      sphingomyelinase. Since DG activates protein kinase C and ceramide indirectly
      inhibits this kinase but activates other kinase(s) and phosphatase(s), the
      phosphocholine transferase at the cell surface may have a regulatory role in
      signal transduction.

PMID- 8294426
TI  - Evidence for two distinct acidic phospholipid-binding sites in cytochrome c.
AB  - Binding of cytochrome c (cyt c) to cardiolipin/phosphatidylcholine (CL/PC) and
      phosphatidylglycerol/PC (PG/PC) liposomes was studied at neutral pH utilizing
      fluorescence resonance energy transfer from a membrane-incorporated pyrene
      phospholipid derivative to the heme of cyt c. ATP in millimolar concentrations
      displaced nearly quantitatively cyt c from membranes containing 17.5 mol% CL or
      30 mol% PG. Notably, increasing the acidic phospholipid/PC molar ratio in the
      liposomes progressively reduced the membrane detachment of cyt c by ATP, and
      practically no dissociation of cyt c from neat PG or CL liposomes was observed.
      Complete dissociation of cyt c from PG/PC liposomes was also produced by
      subsequently added NaCl. However, the concentration of salt required for half
      maximal effect increased upon increasing the PG/PC molar ratio. At 0.1 M NaCl no
      binding of cyt c to neat PG liposomes was observed whereas the extent of membrane
      association of cyt c increased with increasing CL/PC molar ratios also in the
      presence of salt. This difference between CL and PG is attributed to the complex
      electrostatics of the former lipid resulting in its high affinity for protons.
      The above results can be rationalized in terms of two acidic phospholipid-binding
      sites in cyt c. The electrostatically interacting site is constituted by basic
      residues in cyt c and could be identical to the ATP-binding site (Craig, D. B.,
      and Wallace, C. J. A. (1993) Protein Sci. 2, 966-976). In addition there should
      be another lipid-binding site in cyt c with a high affinity to protonated acidic
      phospholipids. Both sites appear to be available for lipid binding at neutral
      bulk pH.

PMID- 8294427
TI  - Interaction of the bHLH-zip domain of c-Myc with H1-type peptides.
      Characterization of helicity in the H1 peptides by NMR.
AB  - The carboxyl-terminal 92 residues of c-Myc-92 display site-specific DNA binding
      specificity for the consensus sequence 5'-CACCACGTGGTG-3' (Blackwell, T. K.,
      Kretzner, L., Blackwood, E. M., Eisenman, R. N., and Weintraub, H. (1990) Science
      250, 1149-1151). Size exclusion high pressure liquid chromatography analysis of
      the purified fusion protein, glutathione S-transferase-c-Myc-92, indicates that c
      Myc-92 is tetrameric with a dissociation constant of < 60 nM. Helix-1 (H1) and
      leucine zipper peptides from the basic-helix-loop-helix-zipper domain of c-Myc
      and Max were assayed as potential inhibitors of c-Myc-92 DNA binding. H1 peptides
      with substitutions that confer greater helicity are found to inhibit c-Myc-92 DNA
      binding. The mechanism of inhibition involves the cooperative binding of H1
      peptides with tetrameric c-Myc-92 as determined by a spectrophotometric assay
      employing 2,4-dinitrophenyl-H1-F8A. NMR structural characterization reveals a
      correlation between helicity and inhibition. In a partially hydrophobic
      environment, H1-Mx (from Max) is a random coil, while H1-WT, H1-F8A, and H1
      F8A,S6A (from c-Myc) display differing degrees of helicity. Structure
      determination on the basis of nuclear Overhauser effect data indicates that the
      H1-F8A helix is significantly more ordered than H1-WT. Analysis on the basis of
      the Max x-ray structure (Ferre-D'Amare, R., Prendergast, G. C., Ziff, E. B., and
      Burley, S. K. (1993) Nature 363, 38-45) suggests that H1 peptide binding to c-Myc
      92 may occur through an alteration in the packing of helix-1 in c-Myc-92 or
      through an interaction with an exposed hydrophobic cluster of residues at each H1
      H2 interface. This binding site for H1 peptides may be of significance in the
      interaction of c-Myc with proteins involved in transcriptional regulation.

PMID- 8294428
TI  - Dual divalent cation requirement of the MutT dGTPase. Kinetic and magnetic
      resonance studies of the metal and substrate complexes.
AB  - Kinetic analyses of both the Mn(2+)- and Mg(2+)-activated hydrolysis of dGTP by
      MutT show the requirement for two divalent cations. Whereas Mn2+ supports a 20
      fold lower kcat (0.19 s-1) than Mg2+ (4.0 s-1), the Km of Mn2+.dGTP (6.3 microM)
      is 45-fold lower than that of Mg2+.dGTP (284 microM). Adenosine 5'-(alpha,beta
      methylenetriphosphate) (AMPCPP) is a linear competitive inhibitor with respect to
      dGTP with a Ki for Mg2+.AMPCPP (42 microM) which is 57-fold lower than the Ki of
      Mg2+.AMPCPP (2.4 mM). Such tightening suggests that a metal-bridge E.M2+.NTP.M2+
      complex is the catalytically active species. The 12 dissociation constants
      describing the quaternary MutT.M2+.AMPCPP.M2+ complex were evaluated for both
      Mn2+ and Mg2+, using EPR and NMR methods. MutT binds a single Mn2+ with a Kd of
      130 +/- 40 microM in reasonable agreement with the kinetically determined
      activator constant of Mn2+ of 230 +/- 72 microM. The MutT.AMPCPP complex binds
      two Mn2+ ions, the weaker of which has a Kd of 16 +/- 2 microM in agreement with
      the kinetically determined KmMn2+ of 26 +/- 10 microM. MutT.Mn2+ binds
      Mn2+.AMPCPP with Kd of 16 +/- 4 microM, whereas MutT alone binds Mn2+.AMPCPP with
      a Kd of 135 +/- 30 microM. The 17-fold enhanced paramagnetic effect of Mn2+ on
      the longitudinal relaxation rate of water protons found with the binary MutT.Mn2+
      complex decreases to 4.7-fold upon binding of AMPCPP and to 8.7-fold upon binding
      of Mn2+.AMPCPP, further supporting a metal-bridge MutT.M2+.NTP.M2+ complex. By
      competition with Mn2+ MutT binds Mg2+ at one site with a Kd of 7.5 mM, and
      MutT.AMPCPP binds Mg2+ at two sites, the weaker of which has a Kd of 0.9 mM.
      These values are comparable to the kinetically determined KaMg of 15 +/- 7 mM and
      KmMg of 1.7 +/- 0.7 mM, respectively. Studies with the racemic, substitution
      inert beta, gamma-bidentate tetraamminecobalt (III)-beta,gamma-phosphate-ATP
      (Co3+(NH3)4ATP) complex show that MutT slowly hydrolyzes only the lambda
      stereoisomer but requires Mg2+ or Mn2+ to do so, confirming a dual metal ion
      requirement.

PMID- 8294429
TI  - Two CGTCA motifs and a GHF1/Pit1 binding site mediate cAMP-dependent protein
      kinase A regulation of human growth hormone gene expression in rat anterior
      pituitary GC cells.
AB  - We established the cis-acting elements which mediate cAMP responsiveness of the
      human growth hormone (hGH) gene in transiently transfected rat anterior pituitary
      tumor GC cells. Analysis of the intact hGH gene or hGH 5'-flanking DNA (5'-FR)
      coupled to the hGh cDNA or chloramphenicol acetyltransferase or luciferase genes,
      indicated that cAMP primarily stimulated hGH promoter activity. Cotransfection of
      a protein kinase A inhibitory protein cDNA demonstrated that the cAMP response
      was mediated by protein kinase A. Mutational analysis of the hGH promoter
      identified two core cAMP response element motifs (CGTCA) located at nucleotides 
      187/-183 (distal cAMP response element; dCRE) and -99/-95 (proximal cAMP response
      element; pCRE) and a pituitary-specific transcription factor (GHF1/Pit1) binding
      site at nucleotides -123/-112 (dGHF1) which were required for cAMP
      responsiveness. GHF1 was not a limiting factor, since overexpression of GHF1 in
      cotransfections increased basal but not forskolin induction levels. Gel shift
      analyses indicated that similar, ubiquitous, thermostable protein(s) specifically
      bound the pCRE and dCRE motifs. The CGTCA motif-binding factors were cAMP
      response element binding protein (CREB)/activating transcription factor-1 (ATF-1)
      related, since the DNA-protein complex was competed by unlabeled CREB consensus
      oligonucleotide, specifically supershifted by antisera to CREB and ATF-1 but not
      ATF-2, and was bound by purified CREB with the same relative binding affinity
      (pCRE < dCRE < CREB) and mobility as the GC nuclear extract. UV cross-linking and
      Southwestern blot analyses revealed multiple DNA-protein interactions of which
      approximately 100- and approximately 45-kDa proteins were predominant; the
      approximately 45-kDa protein may represent CREB. These results indicate that
      CREB/ATF-1-related factors act coordinately with the cell-specific factor GHF1 to
      mediate cAMP-dependent regulation of hGH-1 gene transcription in anterior
      pituitary somatotrophs.

PMID- 8294430
TI  - Phosphorylation of serine 985 negatively regulates the hepatocyte growth factor
      receptor kinase.
AB  - The receptor for hepatocyte growth factor/scatter factor (HGF/SF) is an alpha
      beta tyrosine kinase of 190 kDa which mediates growth and motility in several
      cell types. We have previously shown that tyrosine autophosphorylation enhances
      the receptor kinase activity, while serine phosphorylation by protein kinase C or
      other Ca(2+)-dependent kinase(s) is inhibitory. We now identify Ser985 as the
      major phosphorylation site for the protein kinases responsible for such
      inhibition. Both phorbol esters or Ca2+ ionophore treatment induces
      phosphorylation of the same tryptic phosphopeptide corresponding to the sequence
      Leu983-Arg987 located in the juxta-membrane domain of the receptor beta chain.
      Purified protein kinase C phosphorylates in vitro a synthetic peptide (V14S)
      including Ser985. Trypsin digestion of the phosphorylated V14S generates a single
      phosphopeptide comigrating in reverse-phase high performance liquid
      chromatography with the tryptic peptide phosphorylated in vivo. Phorbol ester
      treatment of cultured cells inhibits the ligand-induced tyrosine
      autophosphorylation of the receptor. In vitro, Ser985 phosphorylation inhibits
      the receptor tyrosine kinase activity on exogenous substrates. Substitution of
      Ser985 by site-directed mutagenesis results in increased tyrosine phosphorylation
      of the receptor and abolishes down-modulation by protein kinase C. These data
      show that phosphorylation of Ser985 is a key mechanism for the negative
      regulation of HGF/SF receptor.

PMID- 8294431
TI  - Membrane potential-linked reversed electron transfer in the beef heart cytochrome
      bc1 complex reconstituted into potassium-loaded phospholipid vesicles.
AB  - The cytochrome bc1 complex purified from beef heart mitochondria was incorporated
      into potassium (K+)-loaded phospholipid vesicles by a cholate dialysis method to
      study the reverse reaction of electron transfer in the complex. The reduction of
      cytochrome b in the presence of sodium ascorbate was observed on addition of
      valinomycin to the K(+)-loaded proteoliposomes in a medium containing no external
      KCl; it was followed by the gradual oxidation. Nigericin accelerated the
      reoxidation of reduced cytochrome b, indicating that a K+ diffusion potential
      (negative inside) induced the reduction of cytochrome b. The extent of the
      cytochrome b reduction depended on the magnitude of the diffusion potential
      across the liposomal membranes, and its maximal reduction was attained at more
      than 210 mV of the diffusion potential. It was cytochrome b562 that was reduced
      during the establishment of the K+ diffusion potential in the presence of
      ascorbate, and about 90% of cytochrome b562 was estimated to be reduced.
      Antimycin A and myxothiazol inhibited the diffusion potential-induced reduction
      of cytochrome b562, and ubiquinone was proved to be essential for the reversed
      electron transfer. The K+ diffusion potential also induced the partial reduction
      of cytochrome b566 when cytochrome b562 had previously been reduced with
      ascorbate plus tetramethyl-p-phenylenediamine. These results were interpreted
      well based on the Q cycle scheme which assumed the energy-dependent reduction of
      ubiquinone at center o. Dicyclohexylcarbodiimide, which did not perturb the
      ability of proteoliposomes to generate the K+ diffusion potential, inhibited the
      energy-dependent reduction of cytochrome b562 without a significant loss in the
      catalytic activity of the complex. The half-inhibition was brought about by 200
      mol of dicyclohexylcarbodiimide/mol of cytochrome c1. These results strongly
      suggest the coupling of a proton flow with the reversed electron transfer in the
      bc1 complex.

PMID- 8294432
TI  - Coupling of endothelin B receptors to the calcium pump and phospholipase C via Gs
      and Gq in rat liver.
AB  - We have demonstrated in liver from male rats that both endothelin A (ETA) and ETB
      receptors coexist in equal proportion and that ETA receptors mediate a calcium
      dependent activation of glycogenolysis. We describe here a sex difference in
      endothelin action in hepatocytes because, in female rats, 80% of the ET receptors
      are of ETB type and, accordingly, activation of glycogenolysis is an ETB-mediated
      process (EC50 = 0.03 pM). ET-1 stimulation of glycogenolysis in female rats was
      consecutive to activation of phosphatidylinositol 4,5-bisphosphate hydrolysis
      (EC50 = 0.03 pM) and to inhibition of the calcium extrusion pump (IC50 = 0.03 pM)
      in plasma membranes, with ET-1 approximately sarafotoxin S6C approximately ET-3.
      Endothelin regulation of each effector was potentiated by GTP gamma S. ET-1 did
      not stimulate adenylyl cyclase activity. To identify the nature of the guanine
      nucleotide regulatory proteins (G protein(s)) coupling ETB receptors to each
      effector, we used antibodies against the COOH terminus of different G protein
      alpha subunits. Antibodies reactive with Gs alpha (RM) blocked ET-1 inhibition of
      the calcium pump, while they did not affect ET-1 stimulation of phospholipase C.
      Antibodies reactive with Gq alpha (QL) dose-dependently antagonized stimulation
      of phospholipase C by ET-1 and vasopressin, without affecting ET-1 inhibition of
      the calcium pump. Antibodies reactive with Gi1 alpha/Gi2 alpha (AS) had no effect
      on either system. We conclude that the calcium signal provoked by endothelins in
      hepatocyte is not only consecutive to activation of phospholipase C but also to
      inhibition of the plasma membrane calcium pump, each effector being coupled to
      ETB receptors by different G proteins, Gq, and Gs.

PMID- 8294433
TI  - The COOH terminus of suppressor of stem loop (SSL2/RAD25) in yeast is essential
      for overall genomic excision repair and transcription-coupled repair.
AB  - We examined several yeast strains with different mutations in the essential SSL2
      (Suppressor of Stem Loop, also called RAD25) gene for their ability to remove
      cyclobutane pyrimidine dimers from expressed genes, and from the genome overall.
      The SSL2 protein has a high degree of amino acid sequence identity to the protein
      encoded by the human ERCC3 gene (Gulyas, K. D., and Donahue, T. F. (1992) Cell
      69, 1031-0142). The mutant allele SSL2-XP encodes a protein resembling the
      mutated ERCC3 protein from UV-sensitive human cells belonging to xeroderma
      pigmentosum complementation group B and Cockayne's syndrome (CS) complementation
      group C (Weeda, G., van Ham, R. C. A., Vermeulen, W., Bootsma, D., van der Eb, A.
      J., and Hoeijmakers, J. H. J. (1990) Cell 62, 777-791; Gulyas and Donahue, 1992).
      The SSL2-XP allele confers UV sensitivity on yeast strain KG119. We found that
      the biochemical basis for the UV sensitivity of KG119 is a complete deficiency in
      the removal of cyclobutane pyrimidine dimers from the overall genome as well as a
      deficiency in transcription-coupled repair. This is the first analysis of the DNA
      repair defect responsible for the UV sensitivity of cells carrying the SSL2-XP
      allele, and it documents the similarity of the defect to that associated with XP
      B/CS-C, and the difference between this defect and that in cells belonging to CS
      complementation groups A and B.

PMID- 8294434
TI  - Protein-polysaccharide interactions. A monoclonal antibody specific for the
      capsular polysaccharide of Cryptococcus neoformans.
AB  - Monoclonal antibodies that react with the capsular polysaccharide, termed
      glucuronoxylomannan (GXM), of Cryptococcus neoformans have potential roles in the
      diagnosis, monitoring of disease progress, and immunotherapy of cryptococcal GXM
      of all four serotypes. A molecular model of the Fab fragment of monoclonal
      antibody 439 was constructed from the amino acid sequence and a template antibody
      molecule, Fab 4-4-20. A tryptophan is present on the surface between light chain
      CDR3 and heavy chain CDR3 in the putative binding site. This tryptophan residue
      proved to be a reporter group, and a fluorescence study of Fab 439 was performed
      to analyze the interaction between cryptococcal GXM and Fab 439. Binding of the
      polysaccharide enhanced the intrinsic fluorescence and caused a blue shift in the
      emission maximum, indicating that the environment of a tryptophan changes from a
      polar to less polar environment. This is consistent with the loss of water from
      the binding site caused by the binding of antigen. This interpretation was
      confirmed by acrylamide quenching, which showed that 1 less tryptophan was
      exposed to solvent in the Fab-GXM complex than in free Fab. Fluorescence
      titration was used to determine binding and dissociation constants (KD). The
      apparent KD values for serotypes A-C were approximately the same; the KD for
      serotype D GXM was 5-11-fold greater. De-O-acetylation of serotype A GXM produced
      a 31-fold increase in the KD, indicating that the O-acetyl groups are important,
      but not essential, for binding. Carboxyl groups appear to be essential for strong
      binding because the KD for carboxyl-reduced GXM was so large that it could not be
      determined.

PMID- 8294435
TI  - Functional domains of recombinant bactericidal/permeability increasing protein
      (rBPI23).
AB  - The 23-kDa recombinant amino-terminal bactericidal/permeability increasing
      protein fragment (rBPI23) has all of the antibacterial and antiendotoxin
      properties of the holoprotein. In the current studies, we have identified
      multiple active domains within rBPI23 with chemical and proteolytic cleavage
      fragments and with synthetic overlapping peptides. We also demonstrate a novel,
      high affinity heparin binding property for rBPI23, in addition to its established
      bactericidal and lipopolysaccharide binding properties. Cleavage fragments and
      synthetic, overlapping peptides of rBPI23 were analyzed for inhibition of the
      lipopolysaccharide-induced Limulus amebocyte lysate reaction, for bactericidal
      activity, and for heparin binding. Three separate, active domains were identified
      in amino acid regions 17-45, 65-99, and 142-169. A single synthetic peptide (85
      99) was bactericidal. These results indicate that rBPI23 is comprised of three
      separate functional domains which contribute to the high affinity interaction of
      rBPI23 with Gram-negative bacteria. The individual activity of each domain and
      the cooperative interaction among domains provide the basis for developing rBPI23
      analogues with increased biologic efficacy.

PMID- 8294436
TI  - Mode of binding of folate analogs to thymidylate synthase. Evidence for two
      asymmetric but interactive substrate binding sites.
AB  - Human thymidylate synthase is a polymeric protein composed of two subunits with
      identical primary structures. In this study we determined the binding affinities
      of 5,10-methylene tetrahydropteroyltetraglutamate (folate substrate) and a group
      of close structural folate analog inhibitors. Thymidylate synthase bound both
      mono and polyglutamylated folate substrates and analogs more tightly in the
      presence of deoxyuridylate. These results and product inhibition studies
      confirmed that the orders of substrate addition and product release from
      thymidylate synthase were similar for mono and polyglutamylated substrates.
      Equilibrium dialysis studies showed that the folate substrate in a ternary
      complex with deoxyuridylate bound to one of the subunits (site A) with a Kd of
      720 nM. The binding of the substrate to the second subunit (site B) was much
      weaker, and the Kd could not be determined by this method. However, dissociation
      constants for each subunit could be measured for the folate analog inhibitors,
      and, depending on the inhibitor, the relative Kd value for each subunit varied
      substantially. For example, formyl-5,8-dideazafolate and tetraglutamylated 10
      propargyl-5,8-dideazafolate bound to both sites with similar Kd values, whereas
      D1694Glu4 bound to subunit A with a higher affinity (Kd = 1.0 nM) than to subunit
      B (Kd = 30 nM). In contrast, 1843U89 (mono or diglutamylated form) had a much
      higher affinity for subunit B (Kd approximately 0.1 nM) compared with subunit A
      (Kd approximately 400 nM). Enzyme inhibition kinetic analyses showed that the Ki
      values of 1843U89 were quite low (0.1 nM) and that the inhibition was
      noncompetitive. In contrast, the other folate analogs inhibited the enzyme via
      mixed inhibition (i.e. both the Km for the folate substrate and the Vmax were
      altered). We conclude that the two subunits of thymidylate synthase bind folate
      substrates and analogs differently and that the asymmetric binding of the ligands
      is the major factor that determines the inhibition kinetics of each folate analog
      inhibitor.

PMID- 8294437
TI  - Promoter analysis of the staphylococcal enterotoxin A gene.
AB  - The promoter region of the staphylococcal enterotoxin A (SEA) gene (sea) of
      Staphylococcus aureus was localized by primer extension analysis in conjunction
      with in vitro mutagenesis. The 5'-end of sea mRNA was located 86 base pairs
      upstream of the translational initiation codon. A DNA region with good agreement
      with canonical promoter sequences was observed beginning 8 base pairs upstream of
      the apparent transcriptional start site. Analysis of a series of progressive
      deletions of upstream DNA revealed that no DNA upstream of the putative -35
      region was required for transcription of sea (determined by primer extension
      analysis) or for SEA production as detected by Western immunoblot analysis.
      Deletion mutants extending into the -35 region or mutants containing nucleotide
      substitutions in the -10 region both showed dramatic reductions in SEA production
      and transcription of sea. Analysis of a deletion mutant in which 59 base pairs
      between the transcriptional and translational start sites were deleted revealed
      slightly increased levels of SEA production.

PMID- 8294439
TI  - The pHin and pHout dependence of the rate of ATP synthesis catalyzed by the
      chloroplast H(+)-ATPase, CF0F1, in proteoliposomes.
AB  - The H(+)-ATPase from chloroplasts was isolated, purified, and reconstituted into
      liposomes from phosphatidylcholine/phosphatidic acid. The rate of ATP synthesis
      was measured after energization of the proteoliposomes by an acid-base transition
      as a function pHout and pHin. At any given pHout, the rate increased sigmoidally
      with increasing internal H+ concentration with half-maximal rates at about pHin
      5.3 for all pHout values between 9.3 and 7.2. At any given pHin, the rate
      decreased sigmoidally with increasing external H+ concentration with half-maximal
      rates at about pHout 7.8. The dependence on internal H+ concentration was
      attributed to the protonation of three monovalent groups with the same pKin, and
      the dependence on external proton concentration to the deprotonation of two
      groups with the same pKout. The following scheme is proposed. The first step of
      the reaction is the binding of three (or four) protons from the inside of the F0
      part, followed by ADP and Pi binding at the F1 part. Then, the enzyme
      conformation is changed, and the proton binding sites are exposed to the outside,
      followed by proton release from F0 and ATP release from F1. The reaction cycle is
      closed by changing the enzyme conformation to the form where protons can bind
      from the inside.

PMID- 8294438
TI  - Expression of a mutant Gi2 alpha subunit inhibits ATP and thrombin stimulation of
      cytoplasmic phospholipase A2-mediated arachidonic acid release independent of
      Ca2+ and mitogen-activated protein kinase regulation.
AB  - The 85-kDa cytoplasmic phospholipase A2 (cPLA2) is the major hormone and growth
      factor-regulated enzyme that catalyzes release of arachidonic acid in mammalian
      cells. Activation of cPLA2 requires elevation of intracellular Ca2+ and the
      phosphorylation of the cPLA2 enzyme by mitogen-activated protein (MAP) kinase.
      Down-regulation of protein kinase C by phorbol esters or pertussis toxin
      catalyzed ADP-ribosylation of Gi proteins inhibits thrombin and ATP receptor
      stimulated MAP kinase and arachidonic acid release, indicating that functional
      protein kinase C and Gi proteins are required for G protein regulation of
      arachidonic acid release. A mutant G alpha i2 subunit having Gly203 mutated to
      Thr (alpha i2G203T) inhibited thrombin and ATP receptor stimulation of
      arachidonic acid release independent of adenylyl cyclase inhibition, Ca2+
      mobilization, and MAP kinase activation. Overexpression of the wild-type alpha i2
      polypeptide or the inactive mutant alpha i2G204A (Gly204 mutated to Ala)
      polypeptide had no effect on thrombin or ATP receptor stimulation of arachidonic
      acid release. The phenotype observed with expression of the mutant alpha i2G203T
      polypeptide defines a role for Gi2 in the control of cPLA2 activity and
      subsequent arachidonic acid release in addition to the regulation of
      intracellular Ca2+ levels and MAP kinase activity.

PMID- 8294440
TI  - Electrostatic and hydrophobic interactions are involved in factor Va binding to
      membranes containing acidic phospholipids.
AB  - The interaction of factor Va with phospholipid monolayers was studied using
      alternating current polarography. For these studies a hanging mercury drop
      electrode is positioned in contact with the monolayer at the air-monolayer
      interface. Factor Va introduced into the aqueous subphase beneath the monolayer
      caused alterations in the capacitance of the circuit. When factor Va was
      introduced beneath monolayers containing 13-25% mole fraction phosphatidylserine
      (PS), 87-75% mole fraction phosphatidylcholine (PC), a significant capacitance
      increase occurred, which is interpreted to be the result of the penetration of
      the factor Va molecules through the monolayer. No penetration or associated
      capacitance changes were observed with monolayers composed of pure PC or pure PS.
      Polarography experiments were also conducted with the electrode placed in the
      aqueous subphase to measure the binding of factor Va to pure PS monolayers. This
      approach has allowed detection of factor Va (at nM concentrations) adsorption to
      a pure PS monolayer. Thus the membrane adsorption process can be distinguished
      from factor Va penetration through the monolayer. These results suggest that
      there are two types of interaction of the factor Va molecule with PS-containing
      monolayers. The interaction with the PS component of the monolayer is essential
      for binding the factor Va (at nM concentrations) that occurs by surface
      adsorption. For mixed PC/PS monolayers, PS adsorption is followed by penetration
      of the protein through the membrane.

PMID- 8294441
TI  - Red blood cell band 3. Lysine 539 and lysine 851 react with the same H2DIDS (4,4'
      diisothiocyanodihydrostilbene-2,2'-disulfonic acid) molecule.
AB  - The band 3 protein of the red blood cell membrane catalyzes anion exchange that
      is inhibited by the stilbenedisulfonate derivative H2DIDS (4,4'
      diisothiocyanodihydrostilbene-2,2'-disulfonic acid). There is one H2DIDS binding
      site per 95,000-Da band 3 polypeptide. The single bound H2DIDS molecule can react
      covalently with 2 different lysine residues. The 2 lysines that react covalently
      with H2DIDS have been localized directly by sequencing fragments of human band 3
      from cells labeled with [3H]H2DIDS. The most rapid covalent reaction is with Lys
      539, in agreement with site-directed mutagenesis studies. The slower reaction is
      with Lys-851, which is known to be the primary site of binding of another anion
      transport inhibitor, pyridoxal phosphate (Kawano et al., 1988). These results
      indicate that the protein is folded to bring these 2 residues into close enough
      proximity to react covalently with the same H2DIDS molecule. In addition to
      defining the residues that react with H2DIDS, these studies have also defined new
      in situ proteolytic cleavage sites in band 3.

PMID- 8294442
TI  - Identification of two SH3-binding motifs in the regulatory subunit of
      phosphatidylinositol 3-kinase.
AB  - Src homology 3 (SH3) domains have been recently shown to bind to proline-rich
      sequences contained in 3BP1, 3BP2, and SOS. In a recent study we demonstrated
      that phosphatidylinositol 3-kinase (PI 3-kinase) associates with the Fyn SH3
      domain. Here we show that p85, the regulatory subunit of PI 3-kinase, binds
      directly to the SH3 domains of Abl, Lck, Fyn, and p85 itself. An examination of
      p85 amino acid sequence revealed two proline-rich sequences in its N-terminal
      region similar to those present in 3BP1, 3BP2, and SOS. To test whether these
      sequences mediate the association of p85 with SH3 domains two peptides with amino
      acid composition corresponding to the p85 alpha proline-rich sequences were
      synthesized and used in competition assays. Both peptides worked equally well in
      inhibiting the binding of PI 3-kinase activity and p85 alpha to Fyn SH3 domain,
      whereas a control peptide had no effect. These results indicate that, as in 3BP1
      and SOS, the proline-rich sequences in p85 mediate its interaction with SH3
      domains. These results also suggest that the SH3 domain of p85 may "self
      associate" with the proline-rich motifs of the same subunit as part of the PI 3
      kinase regulatory mechanism.

PMID- 8294443
TI  - The NH2-terminal alpha-helical domain 1-18 of dermaseptin is responsible for
      antimicrobial activity.
AB  - Dermaseptin, a 34-amino acid residue cationic peptide, was recently shown to
      inhibit the growth of pathogenic fungi responsible for severe opportunistic
      infections accompanying immunodeficiency syndrome and the use of
      immunosuppressive agents. To improve our understanding of the mechanism by which
      dermaseptin exerts its potent antimicrobial action, a series of either NH2- or
      COOH-terminally truncated analogs was synthesized. These analogs were evaluated
      for their ability to inhibit the growth of various pathogenic agents in culture
      medium. Dermaseptin exerted a lytic action upon bacteria, protozoa, yeasts, and
      filamentous fungi at micromolar concentrations. No inhibition of proliferation
      was observed with human KB cells, and dermaseptin did not lyse guinea pig
      lymphocytes or rabbit erythrocytes at doses up to 200 micrograms/ml. Shortening
      the peptide chain of dermaseptin to dermaseptin-(3-34) slightly reduced the
      activity of the peptide, while further reduction of the chain length to residues
      14-34, 16-34, 20-34, and 28-34 yielded peptide derivatives devoid of
      antimicrobial activity. On the other hand, lengthening the peptide chain starting
      from residues 1-4 to residues 1-8 and 1-18 led to a progressive recovery of the
      activity of the parent molecule. Whereas the central core of dermaseptin
      (residues 10-19) was virtually inactive, alteration of the COOH-terminal
      carboxylic group of dermaseptin-(1-18) to a carboxamide yielded a peptide
      exhibiting enhanced antimicrobial potency, yet displaying even less in vitro
      toxicity compared with dermaseptin. Overall, the data indicate that molecular
      elements responsible for the exceptional antimicrobial potency of dermaseptin are
      to be traced to the NH2-terminal alpha-helical amphipathic segment spanning
      residues 1-18 of the molecule. Dermaseptin-(1-18)-NH2 may therefore be considered
      as a useful and highly tractable tool for identifying key features responsible
      for membrane permeabilization and as a starting point for the design of new
      therapeutic agents.

PMID- 8294444
TI  - The reconstituted ADP/ATP carrier activity has an absolute requirement for
      cardiolipin as shown in cysteine mutants.
AB  - Although the site-directed C73S mutation in the ADP/ATP carrier (AAC) AAC2 gene
      from Saccharomyces cerevisiae produced a glycerol-positive strain, indicating
      that the mutant AAC is active, on isolation and reconstitution in egg yolk
      phosphatidylcholine, the C73S AAC had no transport activity, whereas the wild
      type AAC was fully active. Only on addition of cardiolipin was an exchange
      activity with the C73S AAC obtained. The AACs isolated from the other cysteine
      mutants did not (C244S) or only marginally (C271S) require cardiolipin for
      transport on reconstitution. [3H]Carboxyatractylate binding as a measure of
      incorporated AAC molecules was unchanged on addition of cardiolipin in all
      mutants, indicating that cardiolipin does not increase the incorporation of the
      AAC. It also shows that cardiolipin is required only for translocation and not
      for binding. The activity of the C73S mutant AAC shows half-saturation with
      cardiolipin at 2% by weight or at 1.15 mol % in the phosphatidylcholine vesicles.
      Other acidic phospholipids tested such as phosphatidylserine and phosphatidic
      acid did not activate. Among various cardiolipin derivatives, the selectivity for
      cardiolipin is high. Only monolysocardiolipin still retains 12% activity. After
      removal of the bulk of phospholipid, the content of bound phospholipids was
      assayed by 31P NMR. By unmasking with SDS, in the wild-type AAC and in the C73S
      AAC, 6.4 mol and only 1.3 and 2.9 mol of bound cardiolipin/mol of AAC dimer are
      found, respectively. Presumably, on isolation, cardiolipin is lost from the more
      labile C73S mutant AAC. Although the absolute requirement for cardiolipin is
      unique for the C73S AAC, it is concluded that in this mutant, the unmasking of
      the cardiolipin requirement demonstrates a general cardiolipin requirement of the
      wild-type AAC and of AACs from other sources.

PMID- 8294445
TI  - D-myo-inositol 1,4,5-trisphosphate inhibits binding of phospholipase C-delta 1 to
      bilayer membranes.
AB  - The binding of phosphoinositide-specific phospholipase C-delta 1 (PLC-delta 1) to
      bilayer membranes composed of phosphatidylcholine (PC) and phosphatidylinositol
      4,5-bisphosphate (PIP2) was measured in the presence or absence of inositol
      phosphates. Binding was inhibited by the natural D-isomer of myo-inositol 1,4,5
      trisphosphate (D-InsP3), but not by the L-isomer. The concentration of D-InsP3
      required to decrease binding by 50% was 5.4 +/- 0.5 microM. 1-(alpha
      Glycerophosphoryl)-D-myo-inositol 4,5-bisphosphate and D-myo-inositol 2,4,5
      trisphosphate were nearly as effective as D-Ins(1,4,5)P3. D-myo-inositol
      monophosphate with phosphate esterified at either positions 1 or 2 of the myo
      inositol ring, had no significant effect on binding. D-myo-inositol 1,4
      bisphosphate weakly inhibited the binding, whereas the 4,5-isomer was nearly as
      potent as D-InsP3. Neither ATP nor inorganic phosphate significantly affected
      binding. As expected, D-Ins(1,4,5)P3 but not L-Ins(1,4,5)P3 decreased the initial
      rate of PIP2 hydrolysis in bilayer vesicles. The concentration required to
      decrease hydrolysis by 50% was 12.4 +/- 0.5 microM. A catalytic fragment of PLC
      delta 1 that lacks a domain necessary for high affinity PIP2 binding was prepared
      as previously described (Cifuentes, M. E., Honkanen, L., and Rebecchi, M. J.
      (1993) J. Biol. Chem. 268, 11586-11593). In contrast to the native enzyme, the
      rate of PIP2 hydrolysis, catalyzed by the fragment, was not affected by D
      Ins(1,4,5)P3. These data suggest that high affinity binding of the enzyme to PIP2
      and processive catalysis, involve specific recognition of the 4- and 5-position
      phosphates of the inositol ring. Our results are consistent with feedback
      inhibition by the polar head group product, D-Ins(1,4,5)P3, at a step that
      precedes catalysis, namely interfacial recognition.

PMID- 8294446
TI  - Structure of DSG1, the bovine desmosomal cadherin gene encoding the pemphigus
      foliaceus antigen. Evidence of polymorphism.
AB  - The cadherin superfamily of calcium-dependent cell-cell adhesion and recognition
      proteins can be categorized into a number of subsets on the basis of the distinct
      cytoplasmic sequences of their members. Currently these families include
      classical cadherins, desmogleins, desmocollins, protocadherins, and the products
      of the Drosophila genes FAT and Dachsous. Dsg1, the prototype of the desmoglein
      family, is a major component of epidermal desmosomes and the antigenic target of
      antibodies found in the sera of patients with the blistering disease, pemphigus
      foliaceus. In this study, we determined the organization of the bovine DSG1 gene.
      This gene consists of 15 exons distributed over > 37.5 kilobases of genomic DNA.
      A comparison of DSG1 with genes encoding classical cadherins revealed a striking
      conservation of exon boundaries in regions encoding the ectodomain and to a more
      limited extent among those encoding the cytoplasmic domain. Polymorphism was
      found in a sequence of DSG1 encoding protein proximal to the external face of the
      plasma membrane. This region is topologically equivalent to a domain of classical
      cadherins that harbors epitopes recognized by adhesion-disrupting antibodies. We
      discuss these results with regard to the evolution of the cadherin superfamily
      and their implications for the definition of pemphigus epitopes.

PMID- 8294447
TI  - The immunodominant 38-kDa lipoprotein antigen of Mycobacterium tuberculosis is a
      phosphate-binding protein.
AB  - Several antigens of Mycobacterium tuberculosis have been identified by monoclonal
      antibodies and are being exploited in the development of improved vaccines and
      diagnostic reagents, but none has been linked to a specific function. Herein we
      report that the 38-kDa extracellular lipoprotein antigen, the most potent
      immunogen of the mycobacteria, is a phosphate-binding protein with features very
      similar to those of the well characterized periplasmic phosphate-binding protein
      of Escherichia coli which serves as an initial receptor for active transport.
      This is also the first report definitively linking a function of a binding
      protein anchored to a membrane and found in other than Gram-negative bacteria.

PMID- 8294448
TI  - Fusion-mediated microinjection of lysozyme into HepG2 cells through hemagglutinin
      neuraminidase-depleted Sendai virus envelopes.
AB  - The potential of reconstituted Sendai viral envelopes containing only the fusion
      protein (F-virosomes) was evaluated for a targeted cytosolic delivery of lysozyme
      to human hepatoblastoma cells (HepG2) in culture. 125I-Lysozyme loaded into F
      virosomes was used to monitor its fusion-mediated transfer to the HepG2 cells.
      Using fusion assay based on the transfer of water soluble probe, we have
      demonstrated the existence of aqueous connection between F-virosomes and target
      cells. Target specificity of the F-virosomes was ensured by the strong
      interaction between terminal beta-galactose moiety of F protein and the
      asialoglycoprotein receptor on the membrane of HepG2 cells. Incubation of the
      loaded F-virosomes with cells resulted in fusion-mediated injection, as inferred
      from the ability of cells to internalize lysozyme in the presence of azide (an
      inhibitor of the endocytotic process). Binding as well as fusion of the F
      virosomes to HepG2 cells was solely mediated by the F protein. Introduction of
      125I-lysozyme into the HepG2 cells was confirmed by selective accumulation of
      acid and antibody-precipitable radioactivity in the cytosolic compartment. The
      structural integrity of the internalized lysozyme was also assessed. The
      potential usefulness of F-virosomes with defined specificities as biological
      carrier for both in vitro and in vivo cytosolic delivery of macromolecules and
      drugs has been established.

PMID- 8294449
TI  - Melanoma growth stimulatory activity enhances the phosphorylation of the class II
      interleukin-8 receptor in non-hematopoietic cells.
AB  - The class II IL-8 receptor (IL-8R) binds both melanoma growth stimulatory
      activity (MGSA) and IL-8 with high affinity. Reverse transcriptase polymerase
      chain reaction demonstrates that the class II IL-8R mRNA, which has previously
      been detected only in cells of hematopoietic lineage, is also expressed in non
      hematopoietic cell types shown to respond to MGSA or IL-8. To study the signaling
      mechanism by MGSA through the class II IL-8R in non-hematopoietic cells, this
      receptor was overexpressed in the 3ASubE human placental and the 293 human kidney
      cell lines. Membrane preparations of the class II IL-8R expressing 3ASubE
      transfectants exhibited a 2.3 +/- 0.2-fold increase in GTP gamma 35S binding,
      which was sensitive to pertussis toxin, in response to MGSA treatment (0.2
      microM). This MGSA response was not observed in cells transfected with the
      parental expression vector. In vivo phosphorylation studies demonstrated that the
      class II IL-8R was basally phosphorylated in the untreated transfectants, and
      MGSA (5 nM) treatment markedly enhanced the phosphorylation of this receptor. The
      MGSA-induced receptor phosphorylation was both time and concentration dependent
      and could be mimicked by treatment with the calcium ionophore A23187.
      Phosphoamino acid analysis indicated that the MGSA-induced receptor
      phosphorylation was on serine residue(s), suggesting that a serine kinase is
      activated in response to MGSA binding to the class II IL-8R in non-hematopoietic
      cells.

PMID- 8294450
TI  - Protein phosphatase 2A is reversibly modified by methyl esterification at its C
      terminal leucine residue in bovine brain.
AB  - We have recently described a novel protein carboxyl methylation system that
      results in the reversible modification of a 36-kDa polypeptide component of a 178
      kDa protein in the cytosol of a variety of eucaryotic cells. This reaction,
      catalyzed by a cytosolic 40-kDa methyl-transferase, results in the methyl
      esterification of the alpha-carboxyl group of the C-terminal leucine residue. We
      have now purified the major methylated 36-kDa polypeptide from bovine brain. N
      terminal sequence analysis of a tryptic fragment of this polypeptide revealed
      identity to the catalytic subunit of protein phosphatase 2A. This enzyme exists
      in the cell predominantly as a trimeric 151-kDa native species containing the 36
      kDa catalytic polypeptide that terminates in a leucine residue. We then
      fractionated bovine brain cytosolic extracts to separate the major phosphatase
      isoforms 2A1 and 2A2 and found that both could be methylated by a partially
      purified preparation of the methyltransferase. A synthetic C-terminal octapeptide
      based on the sequence of the 36-kDa catalytic subunit is neither a substrate nor
      an inhibitor of this methyltransferase, suggesting that this enzyme recognizes
      aspects of the tertiary and/or quaternary structure of the native phosphatase.
      Because this modification reaction is readily reversible in extracts, it may
      represent a novel strategy of the cell to modulate the function of this protein
      phosphatase.

PMID- 8294451
TI  - Endoglin forms a heteromeric complex with the signaling receptors for
      transforming growth factor-beta.
AB  - Human endoglin is a dimeric protein that binds transforming growth factor-beta
      (TGF-beta). A porcine cDNA clone for endoglin was obtained from a porcine uterus
      cDNA library. The deduced sequence of the primary translated product of endoglin
      consists of 643 amino acids with a high sequence identity (96%) to human endoglin
      in the transmembrane and intracellular domains, but with a lower sequence
      similarity (66%) in the extracellular domain. In contrast to human endoglin,
      porcine endoglin has no Arg-Gly-Asp tripeptide in its sequence. Antibodies,
      raised against a peptide corresponding to the intracellular domain of porcine
      endoglin, immunoprecipitated an 84-kDa protein under reducing condition and a 130
      kDa protein under nonreducing condition in porcine aortic endothelial cells.
      Porcine endoglin bound TGF-beta 1 and -beta 3 efficiently, but TGF-beta 2 less
      efficiently. Endoglin was found to be coimmunoprecipitated with TGF-beta
      receptors type I and/or II by the endoglin antibodies or by TGF-beta receptor II
      antibodies in the presence of ligand. Thus, endoglin and TGF-beta receptors I
      and/or II most likely formed a heteromeric receptor complex. Endoglin was
      phosphorylated on serine residue(s), which did not change after stimulation by
      TGF-beta 1. These results revealed that endoglin is a phosphorylated protein
      which forms a heteromeric complex with signaling receptors for TGF-beta.

PMID- 8294452
TI  - Modulation of inhibitory glycine receptors by phosphorylation by protein kinase C
      and cAMP-dependent protein kinase.
AB  - Recent evidence has suggested a role for phosphorylation in the regulation of
      ligand-gated ion channels. We have recently shown (Ruiz-Gomez, A., Vaello, M.,
      Valdivieso, F., and Mayor, F., Jr. (1991) J. Biol. Chem. 266, 559-566) that the
      inhibitory glycine receptor (GlyR) alpha subunit is phosphorylated in vitro by
      protein kinase C (PKC). In this report we further show that alpha subunits of the
      GlyR can also be phosphorylated by cAMP-dependent protein kinase (PKA) in an in
      vitro assay. Moreover, incubation of intact rat spinal cord neurons with specific
      PKC or PKA activators leads to increased phosphorylation of the GlyR alpha
      subunits, strongly suggesting a physiological role in its functional modulation.
      The role of protein phosphorylation in modulating GlyR channels was explored in
      Xenopus oocytes injected with poly (A)+ mRNA isolated from nervous tissue. The
      treatment of oocytes with phorbol esters or dibutyryl cAMP resulted in a decrease
      or an enhancement, respectively, of glycine-evoked currents. Our results show
      that the GlyR can be phosphorylated in vivo in response to activation of either
      PKC or PKA with opposite functional consequences, suggesting that
      neurotransmitters affecting the activity of such kinases could profoundly alter
      glycine-mediated neuronal signaling and modulate synaptic efficacy.

PMID- 8294453
TI  - Proteolysis and fusion of low density lipoprotein particles independently
      strengthen their binding to exocytosed mast cell granules.
AB  - Contact between low density lipoproteins (LDL) and exocytosed mast cell granules,
      the "granule remnants," leads to binding of LDL to the granule remnants via ionic
      interactions between the apolipoprotein B-100 (apoB-100) component of LDL and the
      heparin proteoglycan component of the granule remnants. Upon incubation at 37
      degrees C, the heparin proteoglycan-bound apoB-100 is progressively proteolyzed
      by remnant chymase and carboxypeptidase A, which are also bound to the heparin
      proteoglycans. Thereupon, the LDL particles fuse, and their binding to the
      granule remnants strengthens, as defined by the decreased ability of NaCl to
      release LDL from the remnants. We now have examined separately the effects of
      proteolysis and fusion on LDL binding. Proteolysis without fusion was induced by
      lowering the incubation temperature to 15 degrees C, and proteolysis-independent
      fusion was induced by treating granule remnant-bound LDL with sphingomyelinase in
      the presence of protease inhibitors. It was found that degradation of the heparin
      proteoglycan-bound apoB-100, even without accompanying particle fusion, increased
      the strength of LDL binding to the granule remnants, suggesting exposure of
      buried heparin binding regions of apoB-100. When such proteolyzed LDL particles
      were allowed to fuse, the strength of their binding to the granule remnants
      increased still further, probably because of an increase in the number of apoB
      100 fragments in the enlarged particles. Proteolysis-independent fusion, induced
      by sphingomyelinase treatment of granule remnant-bound LDL, also increased the
      strength of binding. The results show that proteolytic degradation and fusion,
      the two modifications of granule remnant-bound LDL subsequent to action by
      chymase and carboxypeptidase A of the granule remnants, represent two separate
      mechanisms by which LDL particles become tightly bound to the heparin
      proteoglycans of exocytosed mast cell granules. Since the formation of an
      atheroma, the hallmark of atherosclerosis, is characterized by accumulation in
      the proteoglycan matrix of the arterial intima of extracellular lipid droplets
      resembling the fused LDL particles on the granule remnant surfaces, the
      modifications of LDL described in this study may provide a clue to the actual
      processes by which the lipid droplets are anchored to the arterial intima.

PMID- 8294454
TI  - Structure and expression of the human gene for the matrix metalloproteinase
      matrilysin.
AB  - Matrilysin, a member of the matrix metalloproteinase family, is structurally
      different from the other matrix metalloproteinases by virtue of the absence of a
      conserved COOH-terminal protein domain. In addition, matrilysin mRNA is regulated
      in a specific and distinct manner in normal and malignant tissues. Analysis of
      the genomic structure of the human matrilysin gene revealed that the organization
      of the first five exons is highly conserved among the different members of the
      matrix metalloproteinase family, but that matrilysin contains an atypical sixth
      exon. The promoter region of the matrilysin gene has several features that are
      conserved among several other matrix metalloproteinase family members, including
      the presence of TATA, AP-1, and PEA3 elements. Comparison of the expression of
      the human matrilysin promoter with rat stromelysin promoter/chloramphenicol
      acetyltransferase constructs in HeLa cells revealed that constructs containing AP
      1 and PEA3 elements respond similarly to epidermal growth factor and tumor
      promoter (12-O-tetradecanoyl-phorbol-13-acetate) induction, but that the addition
      of upstream stromelysin sequences results in an increased transcriptional
      activity not observed with upstream matrilysin sequences. The similarities and
      differences observed between the promoters of matrilysin and the other
      metalloproteinases may provide insights into the molecular mechanisms that
      regulate the expression of this family of enzymes as a whole and the factors that
      distinguish the expression patterns of individual family members.

PMID- 8294455
TI  - In vitro analysis of microtubule assembly of isotypically pure tubulin dimers.
      Intrinsic differences in the assembly properties of alpha beta II, alpha beta
      III, and alpha beta IV tubulin dimers in the absence of microtubule-associated
      proteins.
AB  - Microtubule assembly of different beta tubulin isotypes in the presence of 4 M
      glycerol and 6 mM magnesium ion demonstrates significantly different
      characteristics. alpha beta II and alpha beta IV assembled faster and to a
      greater extent than did unfractionated phosphocellulose-purified tubulin (PC
      tubulin). Microtubule assembly from alpha beta III showed a distinctive delay in
      nucleation, proceeded at a slower rate than those of the other beta tubulin
      isotypes, and had the highest critical concentration. However, treatment of beta
      tubulin isotypes with subtilisin to remove the C-terminal domain of the tubulin
      dimer abolished these differences in microtubule assembly pattern and enhanced
      self-assembly. The kinetic analysis of microtubule elongation of different beta
      tubulin isotypes also showed significant differences. Elongation of alpha beta
      III from microtubule seeds had a lower apparent K alpha and a lower apparent Kd
      than did alpha beta II and alpha beta IV. The dynamic behaviors of different beta
      tubulin isotypes were qualitatively similar to each other and fit the dynamic
      instability model. However, microtubules formed from alpha beta III appeared to
      be less dynamic than microtubules formed from other beta tubulin isotypes. Our
      results suggest that the beta III isotype might have a different conformation
      than do the other beta tubulin isotypes. The distinctive nucleation and
      elongation behaviors of the alpha beta III dimers demonstrated in vitro may have
      a significant influence on microtubule functions in vivo.

PMID- 8294456
TI  - In vitro synthesis of human protein synthesis initiation factor 4 gamma and its
      localization on 43 and 48 S initiation complexes.
AB  - The rate of protein synthesis is controlled in a large number of physiological
      situations at the stage of 48 S initiation complex formation, a phase that
      involves the recruitment of mRNA to the 40 S ribosomal subunit. This process is
      mediated by the eukaryotic initiation factor-4 (eIF-4) group of translation
      initiation factors consisting of eIF-4E, eIF-4A, eIF-4B, and eIF-4 gamma. In
      order to develop a new tool to study this process, we have produced radiolabeled
      eIF-4 gamma by in vitro transcription and translation. Despite the fact that eIF
      4 gamma is predicted from the cDNA sequence to be 154 kDa, the major synthetic
      product migrated on SDS-polyacrylamide gel electrophoresis at 205 kDa. Although
      this is similar to the migration of the fastest polypeptide of authentic eIF-4
      gamma (approximately 206 kDa), no products were found to co-migrate with the
      slowest forms of authentic eIF-4 gamma (210-220 kDa), suggesting that these forms
      derive from extensive modification of the initial polypeptide. The in vitro
      product also formed a complex with eIF-4E, as judged by its ability to bind to
      m7GTP-Sepharose. Sucrose gradient sedimentation studies demonstrated that eIF-4
      gamma was present on both 43 and 48 S initiation complexes but not 80 S
      complexes. This supports a model in which free eIF-4E binds to mRNA followed by
      binding of the eIF-4E.mRNA complex to a 43 S initiation complex already
      containing eIF-4 gamma.

PMID- 8294457
TI  - Isolation and characterization of a dibasic selective metalloendopeptidase from
      rat testes that cleaves at the amino terminus of arginine residues.
AB  - A metalloendopeptidase that selectively cleaves doublets of basic amino acids on
      the amino-terminal side of arginine residues was purified to homogeneity from rat
      testes and analyzed further. Two catalytically active forms with apparent
      relative molecular masses of 110,000 and 140,000 Da, respectively, were present
      in the purified preparation of the enzyme. Antibodies raised against the purified
      testis endopeptidase revealed by immunoblot both the 110- and 140-kDa forms in
      both rat testis and brain cortex extracts. The isolated enzyme was inhibited by
      metal chelators and divalent cations. Its activity, lost after preincubation with
      EDTA, was restored by low concentrations of Zn2+ and Mn2+, thus demonstrating the
      metallopeptidase nature of the enzyme. This endopeptidase also exhibited a high
      sensitivity to amastatin (100% inhibition at 20 microM), an aminopeptidase
      inhibitor. A substrate specificity study using physiologically important or
      synthetic peptides containing a processing dibasic site indicated that cleavage
      occurred selectively at the amino-terminal side of an arginine residue,
      independent of the nature of the basic doublet. The enzyme produced such a
      cleavage at the Arg-Lys doublet of somatostatin 28 (Km = 43 microM), at the Arg
      Arg doublet of dynorphin A (Km = 6.45 microM) and atrial natriuretic factor (Km =
      6.25 microM), and at the Lys-Arg doublet of preproneurotensin-(154-170) (Km =
      17.3 microM). Moreover, cleavage efficiency was found to be higher for the larger
      substrates. The distinctive properties of this endopeptidase imply that this
      protein is a member of a novel class of proteolytic enzymes that may be involved
      in the endoproteolytic maturation of hormonal precursors.

PMID- 8294458
TI  - Hypernegative supercoiling of the DNA template during transcription elongation in
      vitro.
AB  - Supercoiled plasmid DNAs with negative superhelicity several times higher than
      normal have been isolated from Escherichia coli topA mutants. The formation of
      these hypernegatively supercoiled plasmid DNAs is apparently induced by
      transcription. We show that hypernegatively supercoiled plasmid DNAs isolated
      from topA mutants contain R-loop(s). To study the mechanism of formation of
      hypernegatively supercoiled plasmid DNA, we have been able to reproduce
      hypernegatively supercoiled DNA in vitro using purified RNA polymerase and DNA
      gyrase. The formation of hypernegatively supercoiled plasmid DNA template in
      vitro is shown to require transcription elongation and is tightly linked to R
      loop formation. We propose that one of the roles of topoisomerase I is to
      suppress R-loop formation during transcription elongation.

PMID- 8294459
TI  - Molecular cloning of a human transmembrane-type protein tyrosine phosphatase and
      its expression in gastrointestinal cancers.
AB  - To determine the expression of various protein-tyrosine phosphatases (PTPs) in
      human gastric cancers, cDNAs encoding conserved PTP domains were amplified by
      reverse transcriptase polymerase chain reaction from KATO-III cell mRNA and
      sequenced. Among 72 polymerase chain reaction clones, one of the cDNA sequences
      encoded a novel potential PTP (stomach cancer-associated PTP, SAP-1). The full
      length (3.9 kilobases) of the SAP-1 cDNA was further isolated from the KATO-III
      cell cDNA library and the WiDr cell cDNA library. The predicted amino acid
      sequence of the SAP-1 cDNA showed that mature SAP-1 consisted of 1093 amino acids
      and a transmembrane-type PTP, which possessed a single PTP-conserved domain in
      the cytoplasmic region. The extracellular region of SAP-1 consisted of eight
      fibronectin type III-like structure repeats and contained multiple N
      glycosylation sites. These data suggest that SAP-1 is structurally similar to
      HPTP beta and that SAP-1 and HPTP beta represent a subfamily of transmembrane
      type PTPs. SAP-1 was mainly expressed in brain and liver and at a lower level in
      heart and stomach as a 4.2-kilobase mRNA, but it was not detected in pancreas or
      colon. In contrast, among cancer cell lines tested, SAP-1 was highly expressed in
      pancreatic and colorectal cancer cells. The bacterially expressed SAP-1 fusion
      protein had tyrosine-specific phosphatase activity. Immunoblotting with anti-SAP
      1 antibody showed that SAP-1 is a 200-kDa protein. In addition, transient
      transfection of SAP-1 cDNA to COS cells resulted in the predominant expression of
      a 200-kDa protein recognized by anti-SAP-1 antibody. SAP-1 is mapped to
      chromosome 19 region q13.4 and might be related to carcinoembryonic antigen
      mapped to 19q13.2.

PMID- 8294460
TI  - Covalent attachment of palmitoleic acid (C16:1 delta 9) to proteins in
      Saccharomyces cerevisiae. Evidence for a third class of acylated proteins.
AB  - Saccharomyces cerevisiae was used as a model system to characterize the covalent
      attachment of palmitoleic acid to proteins. Chemically synthesized cis-[9,10
      3H]hexadecenoic acid (palmitoleic acid) was used to demonstrate the attachment of
      this lipid species to at least six proteins (m = 122, 58, 45, 41, 31, and 17
      kDa). The majority of the labeled proteins are distinct from those labeled with
      [3H]palmitic acid (16:0). Based on the lability of the bond in the presence of
      methanolic KOH or hydroxylamine (pH 8), we propose that [3H] palmitoleic acid is
      attached to proteins via a thioester linkage. The identity of the palmitoleic
      acid was established by C-18 reverse phase high performance thin layer
      chromatography and argentation thin layer chromatography analysis after the fatty
      acid was liberated from the proteins by either transesterification or
      saponification. Incorporation of [3H]palmitoleic acid into proteins was only
      slightly inhibited (relative to [3H] myristic acid) by the presence of
      cycloheximide, indicating that the attachment of [3H]palmitoleic acid occurs post
      translationally. This report is the first description of multiprotein acylation
      by a long chain unsaturated fatty acid.

PMID- 8294461
TI  - Reconstitution in vitro of the valyl-tRNA synthetase-elongation factor (EF) 1
      beta gamma delta complex. Essential roles of the NH2-terminal extension of valyl
      tRNA synthetase and of the EF-1 delta subunit in complex formation.
AB  - Valyl-tRNA synthetase from mammalian cells is isolated exclusively as a complex
      with elongation factor (EF) 1H (the "heavy" form of eukaryotic EF-1, composed of
      subunits alpha, beta, gamma, and delta). In a previous study, the 140-kDa valyl
      tRNA synthetase subunit dissociated from the purified rabbit liver complex was
      shown to display hydrophobic properties, unlike the corresponding yeast
      cytoplasmic enzyme of 125 kDa (Bec, G., and Waller, J.-P. (1989) J. Biol. Chem.
      264, 21138-21143). Compared to the sequence of yeast cytoplasmic valyl-tRNA
      synthetase, that of the human enzyme displays an NH2-terminal extension of
      approximately 200 amino acid residues that bears strong sequence similarity to
      the NH2-terminal moiety of EF-1 gamma (Hsieh, S. L., and Campbell, R. D. (1991)
      Biochem. J. 278, 809-816). We now show that this NH2-terminal extension can be
      selectively excised by elastase treatment of the isolated rabbit valyl-tRNA
      synthetase, without impairing catalytic activity. To examine the role of the NH2
      terminal extension of mammalian valyl-tRNA synthetase in complex formation and to
      identify the subunit(s) of EF-1H responsible for binding the enzyme,
      reconstitution experiments were undertaken. Native or truncated valyl-tRNA
      synthetases were incubated with the isolated EF-1 subunits beta gamma and delta,
      either separately or in combination, and the ensuing products were analyzed by
      chromatography on DEAE-Sepharose FF and Superose 6. The results demonstrate that
      the NH2-terminal extension of valyl-tRNA synthetase is required for complex
      formation and that the enzyme-binding site(s) resides on the EF-1 delta subunit.
      Moreover, although the EF-1 beta gamma binary complex does not bind valyl-tRNA
      synthetase, it is nevertheless required for assembly of a complex of defined
      quaternary structure by preventing the formation of high molecular weight
      aggregates generated in the presence of EF-1 delta alone.

PMID- 8294462
TI  - Decatenating activity of Escherichia coli DNA gyrase and topoisomerases I and III
      during oriC and pBR322 DNA replication in vitro.
AB  - oriC and pBR322 DNA replication, reconstituted with purified replication
      proteins, has been used to study the functional activities of Escherichia coli
      topoisomerase I, DNA gyrase, and topoisomerase III during the final stages of DNA
      replication. In the oriC system, DNA gyrase-catalyzed decatenation of daughter
      DNA molecules was very inefficient, whereas topoisomerase III could catalyze
      complete decatenation. In the pBR322 DNA replication system, almost all the
      daughter DNA molecules could be decatenated by DNA gyrase alone in the absence of
      salt. Decatenation by DNA gyrase in the pBR322 system was completely inhibited,
      without a concomitant inhibition of DNA synthesis, by the addition of
      physiological concentrations of salt. Topoisomerase III, however, could
      decatenate all of the daughter DNA molecules in the pBR322 system, even in the
      presence of high concentrations of salt. A similar effect could not be observed
      in the oriC system, because the addition of salt inhibited DNA synthesis.
      Topoisomerase I was incapable of catalyzing decatenation under any conditions
      examined in either the oriC or pBR322 replication system. The addition of
      topoisomerase I to the replication systems resulted only in an inhibition of DNA
      synthesis.

PMID- 8294463
TI  - Heparin, sulfated heparinoids, and lipoteichoic acids bind to the 70-kDa
      peptidoglycan/lipopolysaccharide receptor protein on lymphocytes.
AB  - The same 70-kDa protein, present on the surface of mouse lymphocytes, served as
      the predominant binding site for heparin, heparinoids, and bacterial lipoteichoic
      acids, as well as peptidoglycan and lipopolysaccharides. This conclusion was
      supported by the following results: (a) all of these compounds photoaffinity
      cross-linked to one major 70-kDa 6.5-7.0 pI protein that co-migrated on two
      dimensional polyacrylamide gel electrophoresis; (b) peptide maps of the 70-kDa
      proteins digested with chymotrypsin, subtilisin, protease V, or papain yielded
      the same peptides for heparin-, lipoteichoic acid-, peptidoglycan-, and
      lipopolysaccharide-binding proteins; (c) cross-linking of peptidoglycan,
      lipopolysaccharide, lipoteichoic acid, and heparin was competitively inhibited by
      the same compounds with the same order of potency, i.e. carboxyl-reduced sulfated
      heparin > peptidoglycan > pentosan polysulfate > heparin > chitin > dextran
      sulfate > trestatin sulfate > polyanetholesulfonate > fucoidan > beta
      cyclodextrin tetradecasulfate > heparan sulfate > carrageenan lambda >
      lipoteichoic acids > Re-lipopolysaccharide > lipopolysaccharide > lipid A >
      polygalacturonic acid; and (d) cross-linking of each of these ligands was not
      inhibited by carboxyl-reduced heparin, dextran, beta-cyclodextrin, trestatin,
      carrageenan kappa, chondroitin 4-sulfate, chondroitin 6-sulfate, beta-D-glucan,
      carboxy-methylcellulose, levan, alpha-D-mannan, and glycogen. The minimum size of
      the molecule that bound was 7-9 glycan residues, whereas, di- and trisaccharides
      did not bind. There was a logarithmic linear relationship between the strength of
      the binding and the length of the polymer (up to > 1500 glycan residues), which
      indicates an avidity effect of the cooperative binding of one polymeric molecule
      to several receptor molecules on the cell surface. The 70-kDa receptor,
      therefore, has a broad, but limited specificity of binding for non-charged
      (peptidoglycan and chitin), highly negatively charged (heparin and heparinoids),
      and weakly negatively charged (lipoteichoic acids, lipopolysaccharides, and lipid
      A) ligands.

PMID- 8294465
TI  - Differential regulation of protein kinase C isozymes by bryostatin 1 and phorbol
      12-myristate 13-acetate in NIH 3T3 fibroblasts.
AB  - Bryostatin 1 and phorbol 12-myristate 13-acetate (PMA) are both potent activators
      of protein kinase C (PKC), although in many systems bryostatin 1 induces only a
      subset of the responses to PMA and blocks those which it does not induce. We
      report here that in NIH 3T3 fibroblasts PMA showed similar potencies for
      translocating PKC isozymes alpha, delta, and epsilon to the Triton X-100-soluble
      and -insoluble fractions and for the down-regulation of the three isozymes.
      Bryostatin 1 was slightly was more potent than PMA for down-regulating it.
      Bryostatin 1 was markedly more potent than PMA for translocating PKC delta but
      showed a biphasic dose-response curve for down-regulating this isozyme. 1-10 nM
      bryostatin 1 down-regulated PKC delta to a similar extent as PMA; lower (10-100
      pM) or, unexpectedly, higher (100 nM to 1 microM) doses of bryostatin 1 caused
      either no or reduced down-regulation. Moreover, these high (100 nM to 1 microM)
      doses of bryostatin 1 inhibited the down-regulation of PKC delta by 1 microM PMA
      when coapplied. Bryostatin 1 caused translocation of PKC epsilon with slightly
      higher potency than PKC delta, but there was no protection of this isozyme at any
      of the doses examined. Bryostatin 1 induced a long-term increase in c-Jun level.
      The dose-response curve for bryostatin 1 was biphasic, with maximal induction at
      1-10 nM bryostatin 1, coincident with the maximal down-regulation of PKC delta.
      We conclude that bryostatin 1 showed substantially different regulation for PKC
      alpha, PKC delta, and PKC epsilon, whereas PMA distinguished only weakly between
      these isozymes.

PMID- 8294464
TI  - REP-2, a Rab escort protein encoded by the choroideremia-like gene.
AB  - Rab escort proteins (REPs) bind to newly synthesized Rab proteins and remain
      bound during and after the attachment of a geranylgeranyl (GG) group by the
      catalytic component of the Rab GG transferase. Transfer of the GG group is
      absolutely dependent on the participation of a REP. REP-1, the first
      characterized REP, is produced by a gene on the X chromosome that is defective in
      patients with choroideremia, a form of retinal degeneration. Cremers et al.
      (Cremers, F.P.M., Molloy, C. M., van de Pol, D. J. R., van den Hurk, J. A. J. M.,
      Bach, I., Geurts van Kessel, A. H. M., and Ropers, H.-H. (1992) Hum. Mol. Genet.
      1, 71-75) isolated a related gene, designated choroideremia-like, which encodes a
      protein that closely resembles REP-1. In the current studies, we produced REP-1
      and REP-2 by recombinant DNA methods and showed that both proteins were
      approximately equal in facilitating the attachment of GG groups to several Rab
      proteins, including Rab1A, Rab5A, and Rab6. However, REP-2 was only 25% as active
      as REP-1 in supporting GG attachment to Rab3A and Rab3D. The low activity toward
      Rab3A was increased to that of Rab1A when the COOH-terminal 12 amino acids of
      Rab3A were replaced with the corresponding residues of Rab1A. We suggest that REP
      2 substitutes for the absent function of REP-1 in nonretinal cells of patients
      with choroideremia, thus preventing cellular dysfunction throughout the body. In
      the retina, REP-2 may be only partially effective, leading eventually to retinal
      degeneration and blindness.

PMID- 8294466
TI  - Regulated cleavage-secretion of the membrane-bound angiotensin-converting enzyme.
AB  - Angiotensin-converting enzyme (ACE) is an ectoprotein anchored in the plasma
      membrane through a hydrophobic domain near its carboxyl-terminal region. Mouse
      epithelial cells transfected with rabbit testicular ACE cDNA, synthesize,
      glycosylate, and secrete ACE by cleavage processing of its membrane-anchoring
      carboxyl-terminal region. Because the cleavage-secretion process is slow, the
      enzyme accumulates on the cell surface. We show that this process can be enhanced
      by treatment of cells with tumor-promoting phorbol esters leading to depletion of
      the cell surface enzyme. The cleavage processing occurs only after the protein
      has reached the cell surface and is not affected by disruption of the Golgi
      apparatus or the lysosomal compartments. The exact peptide bond cleaved has been
      identified by sequencing the amino-terminal residues of the purified COOH
      terminal tail left in the cells after ACE is secreted and the carboxyl-terminal
      residues of secreted ACE. The cleavage occurs at a monobasic site between Arg-663
      and Ser-664 generating the soluble enzyme and leaving a cell-bound protein of 74
      residues. These results demonstrate the existence of cellular mechanisms that
      regulate the conversion of cell-bound ACE to a soluble enzyme.

PMID- 8294467
TI  - High activity and stability of hammerhead ribozymes containing 2'-modified
      pyrimidine nucleosides and phosphorothioates.
AB  - The influence of chemical modifications on the catalytic activity and stability
      of a hammerhead ribozyme directed against the long terminal repeat RNA of the
      human immunodeficiency virus 1 was examined. Previous studies had shown that
      substitution of all pyrimidine nucleosides by their 2'-fluoro analogs led to an 8
      fold decrease in catalytic efficiency in the cleavage reaction compared to the
      unmodified ribozyme (Heidenreich, O., and Eckstein, F. (1992) J. Biol. Chem. 267,
      1904-1909). It is shown here that replacement of the 2'-fluoro-2'-deoxyuridines
      in the conserved region of this ribozyme, positions 4 and 7, by 2'-amino-2'
      deoxyuridines fully restores catalytic activity of the ribozyme. Ribozymes
      containing these 2'-modifications show an increased stability against RNases
      present in fetal calf serum and in cell culture supernatant. The stability is
      increased further by the incorporation of four terminal phosphorothioates as
      protection against 3'-exonucleases, the degree of which depends on the secondary
      structure of the ribozyme. Such ribozymes are stable in undiluted fetal calf
      serum for at least 24 h. The results clearly demonstrate the potential to design
      stable ribozymes without any loss of catalytic activity.

PMID- 8294468
TI  - Id-related genes encoding helix-loop-helix proteins are required for G1
      progression and are repressed in senescent human fibroblasts.
AB  - Three complete cDNA clones encoding Id-related helix-loop-helix (HLH) proteins
      lacking a basic region were isolated from a pcD2 cDNA expression library prepared
      from TIG-3 human diploid fibroblasts (HDF). Of these cDNAs (Id-1H, Id-1H', and Id
      2H), two (Id-1H and Id-1H') appeared to be derived by alternative RNA splicing.
      Id-1H and Id-2H seem to be human homologues of mouse Id-1 and Id-2, respectively,
      and have potential to encode 154 and 135 amino acid proteins. The Id-1H and Id-2H
      mRNAs were barely detectable in quiescent early passage HDF; serum coordinately
      induced both mRNAs, with two peaks of expression, in early and late in G1.
      Antisense oligomers complementary to Id-1H and Id-2H mRNA prevented early passage
      HDF from entering the S phase of the cell cycle. The treatment of serum
      stimulated early passage cells with the antisense Id-1H oligomer completely
      abolished Id-1H. In senescent cells, serum barely induced the Id-1H and Id-2H
      mRNAs, although the levels of c-myc expression induced were similar in early
      passage and senescent cells. The expression levels of these Id genes vary among
      immortal human cell lines. Both genes were overexpressed in VA4 SV40-transformed
      lung fibroblasts and EJ-1 bladder carcinoma cells, while these genes were
      expressed at a very low level in SVts8 cells derived from SV40 tsA-transformed
      TIG-3 cells. SVts8 cells may acquire some function redundant to Id proteins.
      HT1080 fibrosarcoma cells expressed the Id-1H gene but not the Id-2H gene,
      suggesting these Id genes may subserve redundant functions.

PMID- 8294469
TI  - Influence of active site and tyrosine modification on the secretion and activity
      of the Aeromonas hydrophila lipase/acyltransferase.
AB  - Aeromonas sp. secrete a lipase/acyltransferase that shares several properties
      with the mammalian plasma enzyme lecithin:cholesterol acyltransferase. Reaction
      of the enzyme with tetranitromethane led to modification of 2 tyrosines and a
      nearly 80% decline in enzyme activity. Replacing Tyr230 with Phe altered the
      activity of the enzyme in the same way as did treatment with tetranitromethane.
      Unlike the wild type enzyme, which preferentially hydrolyzes the 2-position acyl
      chain of phosphatidylcholine, the Y230F mutant enzyme did not discriminate
      between the 1- and 2-positions of the phospholipid. Tyr230 may be necessary to
      correctly position phospholipid substrates at the active site. Several amino
      acids around the active site Ser16 of the lipase were also changed. Replacing
      Ser18 with Gly, bringing the enzyme's sequence into line with the "lipase
      consensus sequence," resulted in reduced secretion of the protein and complete
      loss of activity. Changing this serine to Val led to an inactive protein that was
      not secreted at all. Substituting Phe13 in the hydrophobic region of the
      consensus sequence with Ser also prevented secretion, although the mutant protein
      appeared to be active. The Aeromonas lipase may represent a distinct group of
      lipolytic enzymes which have a novel active site structure.

PMID- 8294470
TI  - Regulation of hepatocytic glycoprotein sialylation and sialyltransferases by
      peroxisome proliferators.
AB  - Short-term dietary exposure of rats to a representative member of each of the
      three classes of peroxisome proliferators was found to elicit: (i) 71-80 and 66
      75% reductions in the specific activities of the hepatic beta-galactoside alpha
      2,6- and alpha 2,3-sialyltransferases, respectively; (ii) a 67-69% reduction in
      the level of hepatic beta-galactoside alpha 2,6-sialyltransferase protein; and
      (iii) 41-46 and 6-28% reductions in the levels of the hepatic beta-galactoside
      alpha 2,6- and alpha 2,3-sialyltransferase mRNAs, respectively. These changes
      were found to correlate with a reduction in the sialylation of the N-linked
      glycans of a prototypical hepatocytic sialoglycoconjugate, the integral plasma
      membrane glycoprotein CE9, as was evident through: (i) a decrease in apparent
      molecular mass, (ii) a conversion to a more basic distribution of isoelectric
      points, and (iii) 56-72 and 33-44% decreases in the ability to bind lectins
      specific for sialic acid in alpha 2,3- and alpha 2,6-linkage, respectively. When
      assessed by labeling semithin frozen sections of liver tissue with a fluorescent
      lectin specific for alpha 2,6-linked sialic acid, the reduced sialylation
      observed for CE9 was found to extend to other hepatocytic glycoconjugates in the
      livers of peroxisome proliferator-treated rats.

PMID- 8294471
TI  - A protein activator of Ca(2+)-calmodulin-dependent protein kinase Ia.
AB  - A protein activator of Ca(2+)-calmodulin-dependent protein kinase Ia (CaM kinase
      Ia) was purified to near homogeneity from pig brain. In the final step of
      purification, sucrose density gradient centrifugation, CaM kinase Ia activating
      activity correlated with the presence of a approximately 52-kDa protein band
      detected by SDS-polyacrylamide gel electrophoresis. Comparison of this value with
      estimations of its molecular mass under nondenaturing conditions indicated that
      CaM kinase Ia activator is a slightly asymmetric monomer. After removal of
      endogenous CaM kinase Ia activator, the activity of CaM kinase Ia was 2% of its
      activity in the presence of a maximally stimulating concentration (15 nM) of the
      purified activator. In its activated state, CaM kinase Ia retained complete
      dependence of its activity upon Ca(2+)-CaM. The activation of CaM kinase Ia was
      rapid (t1/2 < 1 min) and required the combined presence of CaM kinase Ia
      activator, Ca(2+)-CaM, and MgATP. Similarly, in addition to MgATP, the
      phosphorylation of CaM kinase Ia required CaM kinase Ia activator and Ca(2+)-CaM.
      CaM kinase Ia activator was capable of Ca(2+)-dependent binding to CaM-Sepharose.
      The requirement of the combined presence of CaM kinase Ia activator, Ca(2+)-CaM,
      and MgATP for both the activation and phosphorylation of CaM kinase Ia is
      discussed in terms of potential mechanisms for CaM kinase Ia activation.

PMID- 8294472
TI  - Photochemical cross-linking between native rabbit skeletal troponin C and
      benzoylbenzoyl-troponin I inhibitory peptide, residues 104-115.
AB  - The troponin I (TnI) inhibitory region (residues 104-115) was synthesized with
      alpha-14C-labeled Gly-104 and a covalently linked benzoylbenzoyl (BB) moiety at
      the N terminus to yield a photoactivatable radioactive peptide (BBIp). BBIp was
      cross-linked to rabbit skeletal muscle troponin C (TnC) to locate the binding
      site on TnC. The TnC/BBIp mixture was subjected to photolysis in aqueous buffer
      at pH 7.5 in the presence or absence of Ca2+. A covalent (1:1) cross-linked
      protein-peptide complex (TnC.BBIp) was isolated in both cases. The cross-linked
      complex was digested with trypsin, and the peptide fragments were separated by
      reversed-phase high performance liquid chromatography. The radioactive cross
      linked peptide was isolated and further characterized by peptide sequencing and
      mass spectrometry before and after cyanogen bromide cleavage. The results
      indicated that Met-155 of TnC was cross-linked to the BB moiety of BBIp in either
      the presence or absence of Ca2+. The biological activity of both the BBIp peptide
      and the cross-linked TnC.BBIp complex was studied and a model of the
      TnC.inhibitory peptide complex was derived using molecular dynamic and energy
      minimization calculations.

PMID- 8294473
TI  - Structure, chromosome location, and expression of the human very low density
      lipoprotein receptor gene.
AB  - Isolation and characterization of cDNAs encoding human very low density
      lipoprotein (VLDL) receptor revealed the presence of two forms of the receptor:
      one consists of five domains that resemble the low density lipoprotein (LDL)
      receptor, and a variant form lacks an O-linked sugar domain. More than 96% of
      amino acids in the human and rabbit VLDL receptors are identical, whereas those
      in the LDL receptors are less conserved between the two species (76%). The human
      VLDL receptor gene contains 19 exons spanning approximately 40 kilobases. The
      exon-intron organization of the gene is almost the same as that of the LDL
      receptor gene, except for an extra exon that encodes an additional repeat in the
      ligand binding domain of the VLDL receptor. Analysis of DNA from human-rodent
      hybrid cells revealed that the gene is located on chromosome 9. Although the 5'
      flanking region of the VLDL receptor gene contains two copies of a sterol
      regulatory element-1 like sequence, the levels of mRNA for the receptor in THP-1
      human monocytic leukemia cells were unchanged by sterols. The 5'-untranslated
      region of the receptor mRNA contains a polymorphic triplet repeat found also in
      the fragile X syndrome gene.

PMID- 8294474
TI  - Studies on pig aldose reductase. Identification of an essential arginine in the
      primary and tertiary structure of the enzyme.
AB  - Reaction of pig muscle aldose reductase with phenylglyoxal resulted in the
      chemical modification of 2 arginine residues with accompanying loss of catalytic
      activity. The amino acid sequences of radioactive peptides resulting from the
      reaction of aldose reductase with [14C]phenylglyoxal followed by tryptic
      digestion and high performance liquid chromatography separation allowed
      identification of the modified arginine residues as R268 and R293. In the
      presence of the coenzyme NADP+, R268 is protected from modification by
      phenylglyoxal, while R293 becomes hyper-reactive. Phenylglyoxal modification of
      aldose reductase is slowed 3-fold by the presence of the coenzyme analog ADPRP;
      however, both arginines are still modified. These chemical modification results
      are in complete accord with the previously determined crystal structures of human
      and porcine aldose reductase complexed with NADPH, NADP+, and ADPRP. These
      structures indicate that R268 is located at the adenosine binding site, salt
      bridged to the 2'-phosphate group of NADP(H) and ADPRP. Arginine 293 is near the
      surface of the enzyme and is part of the C-terminal loop. In the apoenzyme or the
      ADPRP complex, R293 is partially protected by loop 7; upon binding NADP(H), loop
      7 folds down over the coenzyme, thus exposing R293 to solvent. Our modification
      studies provide further evidence of the conformational change that occurs during
      the aldose reductase catalytic cycle.

PMID- 8294475
TI  - Phosphorylation-dependent interaction of adenovirus preterminal protein with the
      viral origin of DNA replication.
AB  - Adenovirus preterminal protein (pTP) exists as a heterodimer with the viral DNA
      polymerase (AdPol) and becomes covalently linked to a dCMP residue during
      initiation of DNA replication. The in vivo phosphorylation of pTP could be
      demonstrated when pTP is overproduced using recombinant vaccinia viruses, or by a
      large scale metabolic labeling of adenovirus 2 (Ad2)-infected HeLa cells.
      Phosphoserine was the only phosphoamino acid obtained by acid hydrolysis of 32P
      labeled pTP immunoprecipitated from metabolically labeled HeLa cells infected
      with either Ad2 or recombinant vaccinia virus. Tryptic peptide maps of pTP
      expressed using recombinant vaccinia virus system in HeLa cells revealed that
      phosphorylation of pTP occurred on multiple sites. Dephosphorylation of pTP with
      calf intestinal alkaline phosphatase resulted in a significant decrease in its
      activity in the in vitro DNA replication initiation assays. Further
      characterization of the phosphatase-treated pTP indicated that although
      dephosphorylation did not affect its interaction with AdPol, the specific
      recognition of the DNA replication origin by pTP was significantly reduced as
      determined by gel electrophoresis-based DNA mobility shift assays.

PMID- 8294476
TI  - DNA sequence affects nucleosome ordering on replicating plasmids in transfected
      COS-1 cells and in vitro.
AB  - Nucleosome ordering on a variety of replicating plasmids, assembled into
      chromatin in transfected COS-1 cells, was studied by micrococcal nuclease
      digestion of isolated nuclei. Generally, no more than three well defined
      multiples of a unit nucleosome repeat, which resembled the first three bands of
      the (187 +/- 5 base pair (bp)) cellular chromatin ladder, could be detected in
      constructs that contained a near-minimal SV40 replication origin. In contrast,
      constructs that additionally contained the SV40 early region exhibited
      significantly more regular nucleosome arrangements. In some cases, eight to nine
      multiples of a 203 +/- 5-bp repeat could be resolved. The presence of the SV40
      early region was necessary for physiological nucleosome alignment over the SV40
      late and ori regions, or onto adjacent pBR327 DNA. In an in vitro chromatin
      assembly system, using purified chicken erythrocyte histones plus polyglutamic
      acid, a portion of SV40 DNA became packaged into a highly ordered 200 +/- 5-bp
      nucleosome array, which encompassed the early region and extended for about 2800
      bp. The data suggest that in the cell nucleus, nucleosome ordering on SV40 DNA
      might spread from sequences in the early region, close to where transcription
      terminates, probably as a consequence of histone H1-nucleosome interactions.

PMID- 8294477
TI  - PDR5, a novel yeast multidrug resistance conferring transporter controlled by the
      transcription regulator PDR1.
AB  - The complete sequence of the pleiotropic drug resistance gene PDR5 from
      Saccharomyces cerevisiae is reported and analyzed. PDR5 encodes a 160-kDa protein
      with a predicted duplicated six membrane-span domain and a repeated putative ATP
      binding domain. PDR5 shares this structural feature with the mammalian multidrug
      resistance pumps as well as the functional capacity of conferring resistance to
      various inhibitors upon amplification (Leppert, G., McDevitt, R., Falco, S. C.,
      Van Dyk, T. K., Ficke, M. B., and Golin, J. (1990) Genetics 125, 13-20). The
      yeast PDR5 is thus a new member of the ABC (ATP-binding cassette) protein
      superfamily. Mutations in another yeast pleiotropic drug resistance gene, PDR1,
      encoding a putative transcription regulator (Balzi, E., Chen, W., Ulaszewski, S.,
      Capieaux, E., and Goffeau, A. (1987) J. Biol. Chem. 262, 16871-16879), increase
      markedly the mRNA levels of the PDR5 and STE6 genes. The multidrug resistance
      mutations pdr1-3 and pdr1-6 also lead to considerable overexpression of the PDR5
      plasma membrane protein.

PMID- 8294478
TI  - Species-specific changes in regulatory elements of mouse haptoglobin genes.
AB  - Although expression of the haptoglobin (HP) as an acute phase reactant is
      evolutionarily conserved among mammals, there are differences among species with
      regard to the hormones required for stimulation. Using primary hepatocyte
      cultures, we show that in Mus caroli, as in rat, IL-1 and IL-6 are stimulatory,
      whereas in M. domesticus, as in humans, IL-1 response is diminished. In vivo, an
      acute inflammatory process increases hepatic HP expression in both mouse species
      up to 30-fold but minimally affects the low level HP expression in the lung. To
      define the species-specific differences in regulation, we isolated the hormone
      responsive elements of the HP gene from the Mus species, M. domesticus, M.
      caroli, and M. saxicola. Functional studies in transfected hepatoma cells
      revealed an exceptionally strong dexamethasone response for all three murine HP
      gene elements. The IL-6 response was less prominent than in rat or human. A
      modest response to IL-1 was observed in M. caroli and M. saxicola. A mouse
      specific insertion of a polypurine sequence led to a binding site for the PEA3
      transcription factor in the HP gene promoter of M. domesticus and M. saxicola,
      but not M. caroli. The specific regulatory effects of glucocorticoid receptor,
      C/EBP beta, and Ets proteins were documented by co-transfection.

PMID- 8294479
TI  - Isolation and initial characterization of the bipartite contractile vacuole
      complex from Dictyostelium discoideum.
AB  - The contractile vacuole complex serves to excrete excess cytosolic water from
      protists. In the amoeba, Dictyostelium discoideum, the organelle had a bipartite
      morphology: a large main vacuole (bladder) marked by lumenal alkaline phosphatase
      was surrounded by numerous satellite vacuoles (spongiomes). Bladders and
      spongiomes have now been purified for the first time. The spongiome membranes had
      a high density of surface projections identified as catalytically-active vacuolar
      proton pumps (V-H(+)-ATPase). Spongiomes were resolved from the pump-poor
      bladders by immunogold buoyant density shift with antibodies to the V-H(+)
      ATPase; they contained little protein other than this pump. It appears that,
      following homogenization, most of the spongiome dissociated from bladders and
      populated the proton pump-rich membrane fraction called acidosomes. Isolated
      bladders were enriched > 40-fold in alkaline phosphatase and phosphodiesterase,
      the activities of which were > 85% latent. Bladders depleted of spongiomes bore
      several distinctive polypeptides; they also had an excess of the basepieces of
      the proton pump over the catalytic heads. Bladder membranes were also lipid-rich
      and had a distinctive lipid composition. We conclude that the contractile vacuole
      system in Dictyostelium is a complex of discrete, separable bladder and spongiome
      membranes. The V-H(+)-ATPase in the spongiome may catalyze the primary energy
      transduction step for pumping water out of the cytoplasm.

PMID- 8294480
TI  - Activation of gastrin transcription in pancreatic insulinoma cells by a CACC
      promoter element and a 70-kDa sequence-specific DNA-binding protein.
AB  - Gastrin gene expression in the pancreatic islets is developmentally regulated and
      occurs largely during fetal life. Deletional analysis of transiently transfected
      rat insulinoma cells with gastrin 5'-flanking sequences in luciferase reporter
      genes demonstrated that the gastrin promoter sequence proximal to -111 base pairs
      (bp) contains the cis-regulatory elements necessary for maximal transcription.
      Mutational analysis identified the sequence CCCCACCCCA (-109 to -100 bp) as a
      positive cis-regulatory element (CACC) located 5' to a previously described
      negative element (-100 to -90 bp) and E-box positive element at -82 bp. Multimers
      of the CACC element in a heterologous promoter activated transcription
      independent of the other cis-regulatory elements. CACC binding proteins were
      purified from insulinoma cell nuclear extracts by cation exchange and affinity
      chromatography. Southwestern blot of nuclear extracts identified a 70-kDa CACC
      binding protein. Mutational analysis of the CACC element showed a close
      correlation between DNA binding of this protein and transcriptional activation.
      Transcriptional activation by multimers of the CACC element in a heterologous
      promoter was detected in a variety of cell lines but was strongest in those of
      islet lineage. Likewise, the presence of the 70-kDa CACC-binding protein was
      found in many cell lines but was most abundant in the insulinoma cells. The CACC
      binding protein has not been previously identified among the known pancreatic
      regulatory factors and may have an important role in the developmental expression
      of gastrin.

PMID- 8294481
TI  - Monomeric Re lipopolysaccharide from Escherichia coli is more active than the
      aggregated form in the Limulus amebocyte lysate assay and in inducing Egr-1 mRNA
      in murine peritoneal macrophages.
AB  - Using the equilibrium dialysis apparatus, an aqueous suspension of predominantly
      aggregated Re lipopolysaccharide (ReLPS) from Escherichia coli D31 m4 (99.9% at
      82.5 microM) can be processed to yield a solution of monomeric ReLPS at a
      saturation concentration of 77 ng/ml (3.4 x 10(-8) M). We compared the in vitro
      biological activities of these two physically distinct types of ReLPS
      preparations in two select assays, reaction in the Limulus amebocyte lysate (LAL)
      assay and induction of Egr-1 mRNA in macrophages. These assays were chosen for
      their rapid response times and relatively short incubation periods. The monomeric
      ReLPS was 179- and 1000-fold more active than the aggregated ReLPS preparation in
      the LAL assay and induction of Egr-1 mRNA by thioglycollate-elicited murine
      peritoneal macrophages, respectively. These results clearly showed that the
      monomeric ReLPS is the more active form. The lower biological activities of the
      aggregated ReLPS preparation might be due to the presence of a small amount of
      monomeric ReLPS (0.01-0.6%) produced during its preparation and the incubation
      periods in the biological assays. Thus, aggregated ReLPS may be relatively
      inactive.

PMID- 8294482
TI  - Dual control of inositol transport in Saccharomyces cerevisiae by irreversible
      inactivation of permease and regulation of permease synthesis by INO2, INO4, and
      OPI1.
AB  - Uptake of inositol by Saccharomyces cerevisiae is regulated through
      transcriptional control of the gene that encodes the major inositol permease,
      ITR1 (Nikawa, J., Tsukagoshi, Y., and Yamashita, S. (1991) J. Biol. Chem. 266,
      11184-11191). ITR1 mRNA abundance decreases when cells are transferred from
      medium without inositol to medium with inositol. Here we demonstrate that the
      mechanism of transcriptional regulation of ITR1 is through the action of the
      INO2, INO4 and OPI1 genes. INO2 and INO4 are required for derepressed levels of
      ITR1 mRNA, and OPI1 is necessary for repression of transcript levels in response
      to inositol. The INO2, INO4, and OPI1 genes thus coordinate uptake of inositol to
      endogenous inositol biosynthesis and to phospholipid biosynthesis. Repression of
      transcription of ITR1 also requires ongoing synthesis of phosphatidylcholine,
      defining an additional link between synthesis of phospholipids and regulation of
      inositol uptake. Analysis showed that the INO1 gene, encoding a key enzyme in the
      inositol biosynthetic pathway, responded to decreases in permease activity with a
      graduated increase in the level of INO1 mRNA. We also found that, in addition to
      the transcriptional regulation, inositol permease activity is regulated by
      irreversible inactivation. Inactivation of the ITR1 permease occurs in response
      to the presence of inositol and involves a change in the functional half-life of
      the protein.

PMID- 8294483
TI  - Identification and characterization of SET, a nuclear phosphoprotein encoded by
      the translocation break point in acute undifferentiated leukemia.
AB  - The translocation (6;9) in acute nonlymphocytic leukemia results in the formation
      of a dek-can fusion gene. In a case of acute undifferentiated leukemia, the
      oncogene can is fused to a different gene, named set, instead of dek and is
      assumed to be activated. Transcripts of set encode a putative SET protein with a
      predicted molecular mass of 32 kDa. We identified SET as a 39-kDa protein by
      immunoprecipitation with rabbit antiserum against each of three synthetic
      peptides predicted from the open reading frame of the set gene. We confirmed this
      identification of SET by protein sequencing. We also observed that SET is
      expressed ubiquitously in various human cell lines. SET is phosphorylated on
      serine residue(s) in cultured cells and is localized predominantly in nuclei.
      Although the function(s) of SET and SET-CAN is not known, we propose that SET
      plays a key role in the mechanism of leukemogenesis in acute undifferentiated
      leukemia, perhaps by activating CAN in nuclei and stimulating the transformation
      potential of SET-CAN. This proposed role would therefore be similar to the roles
      observed for BCR and DEK of the chimeric oncoproteins BCR-ABL and DEK-CAN in
      acute myeloid leukemia and acute nonlymphocytic leukemia, respectively.

PMID- 8294484
TI  - Purification of the NADH:ubiquinone oxidoreductase (complex I) of the respiratory
      chain from the inner mitochondrial membrane of Solanum tuberosum.
AB  - The plant NADH:ubiquinone oxidoreductase (or complex I) was isolated from potato
      (Solanum tuberosum) mitochondria. The multisubunit enzyme was solubilized with
      detergents, Triton X-100 and 3-[(3-cholamidopropyl)dimethylammonio]-1
      propanesulfonate (CHAPS), out of the inner mitochondrial membranes and purified
      by hydroxylapatite and gel filtration chromatography. The preparation was found
      to be virtually free of any ATPase or transhydrogenase contamination. Complex I
      of potato is composed of at least 32 individual subunits as detected in silver
      stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis and has a total
      molecular mass of about 900 kDa. The enzyme preparation showed an NADH:ubiquinone
      2 reductase activity of 11.5 mumol x min-1 x mg-1 and is strongly inhibited by
      rotenone. Heterologous polyclonal antibodies against the 70- and 49-kDa subunits
      of the Neurospora crassa complex I and against the wheat NAD9 subunit cross
      reacted specifically with the respective potato subunits. Four of the 10 NH2
      terminal sequences determined show significant similarities to Neurospora or
      bovine complex I subunits and allow a tentative assignment of these subunits.

PMID- 8294485
TI  - Molecular cloning and expression of a glycosaminoglycan N-acetylglucosaminyl N
      deacetylase/N-sulfotransferase from a heparin-producing cell line.
AB  - Heparin has a higher content of N-sulfated glucosamine and L-iduronic acid than
      heparan sulfate. Deacetylation of N-acetylglucosamine followed by N-sulfation may
      be important steps differentiating the biosynthesis of these glycosaminoglycans.
      We have cloned, by cross-hybridization with the cDNA from rat liver heparan
      sulfate N-deacetylase/N-sulfotransferase, a protein from a heparin synthesizing
      mastocytoma derived cell line called MST. This protein, which has both N
      deacetylase/N-sulfotransferase activities, has a predicted amino acid sequence
      homology of 70% with the above rat liver enzyme and is unique for the following
      reasons. 1) It was found to be encoded by a 3.8-kilobase mRNA that was unique to
      heparin-producing cells; an 8.5-kilobase mRNA encoding the rat liver enzymes has
      been found to occur in all mammalian cells tested on the basis of nucleic acid
      cross-hybridization; 2) the protein overexpressed in COS cells in its full-length
      transmembrane form or as a soluble secreted protein A chimera displayed ratios of
      N-deacetylase to N-sulfotransferase activities that were 4-8-fold higher than
      that observed for the enzyme found in liver that is involved in the biosynthesis
      of heparan sulfate. These results suggest that the MST-derived enzyme is probably
      unique to the production of heparin in mast cells.

PMID- 8294486
TI  - Analysis of acceptor stem base pairing on tRNA(Trp) aminoacylation and function
      in vivo.
AB  - The role of acceptor stem base pairs in determining the identity of Escherichia
      coli tRNA(Trp) was examined by complementation of an E. coli strain containing a
      temperature-sensitive tRNA(Trp) gene (trpTts) and by monitoring aminoacylation
      levels in vivo. All derivatives of tRNA(Trp) containing substitutions at the
      first 3 base pairs in the acceptor stem complemented the trpTts mutation at the
      nonpermissive temperature (42 degrees C). However, three acceptor stem
      derivatives (tRNA(Trp)/C1.G72, tRNA(Trp)/C2.G71, and tRNA(Trp)/A3.U70) required
      overexpression for growth at 42 degrees C. Northern analysis of these derivatives
      following acid/urea gel electrophoresis showed no defects in tRNA aminoacylation
      at the nonpermissive temperature. Instead, these tRNAs appear to be defective in
      translation. This was suggested by the weak opal suppressor activities of the
      corresponding tRNA(UCATrp) derivatives. These results demonstrate that the three
      terminal acceptor stem base pairs do not contribute to the identity of tRNA(Trp).
      Substitution of the C1.A72 base pair in a methionine initiator tRNA containing
      the tryptophan anticodon and discriminator base (tRNA(CCAfMet)/G73) with A1.U72,
      the base pair found in tRNA(Trp), or G1.C72 resulted in the conversion of these
      tRNAs into tryptophan-inserting elongator tRNAs in vivo. However, changes to
      U1.A72 or C1.G72 in tRNA(CCAfMet)/G73 resulted in misaminoacylation and/or
      defects in translation. Our data indicate that the A1.U72 base pair is a context
      dependent, negative identity element of tRNA(Trp).

PMID- 8294487
TI  - Analysis of human acid beta-glucosidase by site-directed mutagenesis and
      heterologous expression.
AB  - Structure/function relationships of acid beta-glucosidase, the enzyme deficient
      in Gaucher disease, were evaluated by characterizing the proteins expressed from
      cDNAs encoding normal and mutant enzymes. Twenty-two Gaucher disease mutations or
      created mutations were expressed in Spodoptera frugiperda (Sf9) cells and
      analyzed for catalytic properties, stability, inhibitor binding, and modifier
      interactions. Many Gaucher disease mutations encoded highly disruptive amino acid
      substitutions (e.g. P289L and D409V) and produced severely compromised proteins
      with very reduced activity (kcat < 1% of normal) and/or stability. Six mutant
      enzymes had sufficient catalytic activity (kcat approximately 5-30% of normal)
      for extensive studies. The highly conservative substitutions, i.e. F216Y or S364T
      and V394L, led to severe, but selective, abnormalities of enzyme stability or
      large decreases in catalytic activity, respectively. The T323I, N370S, and V394L
      enzymes interacted abnormally with active site-directed inhibitors and localized
      these residues to the glycon binding region. Selected mutant enzymes were poorly
      activated by phosphatidylserine (V394L, L444P, and R463C) or by saposin C (L444P
      and T323I), indicating that the enzyme sites for interaction with these
      activators were within the carboxyl one-third of the enzyme. Substitutions of
      Ser, Glu, and/or Gly at residues Asp-443 and/or Asp-445 demonstrated important
      steric roles for these residues in the active site, but neither is the catalytic
      nucleophile. Together with previous studies, the present analyses provide an
      insight into the pathogenesis of Gaucher disease and the functional organization
      of acid beta-glucosidase.

PMID- 8294488
TI  - Ubiquinone binding domains in bovine heart mitochondrial cytochrome b.
AB  - Cytochrome b was identified as one of the ubiquinone-binding proteins in bovine
      heart mitochondrial ubiquinol-cytochrome c reductase by photoaffinity labeling
      using 3-azido-2-methyl-5-methoxy-6-(3,7-dimethyl[3H]-octyl)-1,4-benzoquinone
      ([3H]azido-Q). The [3H]azido-Q-labeled cytochrome b protein was purified to
      homogeneity from the azido-Q-labeled ubiquinol-cytochrome c reductase by a
      procedure involving Triton X-100 and urea treatment, calcium phosphate column
      chromatography, acetone precipitation, decanoyl-N-methylglucamide-cholate
      extraction, and preparative sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Purified cytochrome b protein containing 0.5 mol of azido-Q/mol
      of protein was subjected to reductive carboxymethylation and succinylation prior
      to digestion by chymotrypsin. Two azido-Q-linked peptides with retention times of
      47.1 and 49.0 min were obtained by high performance liquid chromatographic
      separation. Partial amino-terminal amino acid sequences of these two peptides
      were determined to be GATVI- and ALVADL-, indicating that these two chymotryptic
      peptides are from amino residues 142-155 and 326-336. Monospecific polyclonal
      antibodies against two synthetic ubiquinone-binding peptides, NH2-G-A-T-V-I-T-N-L
      L-S-COOH (P-47) and NH2-W-A-L-V-A-D-L-L-T-L-T-W-I-COOH (P-49), were generated in
      rabbits and purified. Western blotting and enzyme-linked immunosorbent assays
      showed that the purified antibodies against P-47 reacted with cytochrome b
      containing reductases and purified cytochrome b protein. Antibodies against P-47
      inhibited activities of succinate-cytochrome c and ubiquinol-cytochrome c
      reductases only when they were incubated with phospholipid-depleted reductases
      prior to the replenishment with phospholipid. No inhibition was observed with
      incubation with phospholipid-containing reductases, indicating that this peptide
      involved in ubiquinone binding is buried in a phospholipid environment.

PMID- 8294489
TI  - Transfected platelet-activating factor receptor activates mitogen-activated
      protein (MAP) kinase and MAP kinase kinase in Chinese hamster ovary cells.
AB  - The platelet-activating factor (PAF) was seen to potently activate mitogen
      activated protein (MAP) kinase and MAP kinase kinase through the cloned guinea
      pig PAF receptor stably expressed in Chinese hamster ovary (CHO) cells. Both 42-
      and 44-kDa MAP kinases were activated and tyrosine-phosphorylated in response to
      PAF. The PAF receptor also triggered the production of inositol phosphates and
      the release of arachidonic acid and inhibited cyclic AMP accumulation.
      Differential inhibitory effects of pertussis toxin (PTX) on these signals
      suggested that the PAF receptor couples to both PTX-sensitive and -insensitive G
      proteins in CHO cells. MAP kinase and MAP kinase activations were partially
      regulated by PTX-sensitive G proteins. The PAF receptor did not trigger any
      detectable increase in the GTP form of Ras under the conditions in which the
      human insulin receptor expressed in the same parent CHO cells potently increased
      the level. Since these agonists induced comparable MAP kinase activations through
      cognate receptors, Ras seems to play different roles in MAP kinase activation by
      the two different classes of receptors. The activation of MAP kinase by the
      cloned PAF receptor may explain part of the mechanisms underlying PAF-induced
      differentiation and proliferation in non-inflammatory cells.

PMID- 8294490
TI  - Overexpression of human apolipoprotein C-III in transgenic mice results in an
      accumulation of apolipoprotein B48 remnants that is corrected by excess
      apolipoprotein E.
AB  - Overexpression of human apolipoprotein (apo) C-III in the plasma of transgenic
      mice results in hypertriglyceridemia, with up to a 20-fold elevation in plasma
      triglyceride. Nearly all of the triglyceride accumulates in the d < 1.006 g/ml
      lipoprotein fraction, which consists predominantly of apoB48-containing particles
      having a low apoE:apoB48 ratio in contrast to normal mice. The transgenic and
      nontransgenic d < 1.006 g/ml lipoproteins are similar in size, and they are
      equivalent substrates for lipoprotein lipase in vitro. Total apoB100 levels are
      similar in transgenic and normal plasma, but apoB48 levels are increased in
      transgenic mice. The transgenic d < 1.006 g/ml particles are poor competitors for
      the binding of low density lipoproteins to the low density lipoprotein receptor
      in vitro, which is corrected by the addition of exogenous apoE. The rate of
      clearance of labeled chylomicron remnants in apoC-III-transgenic mice was about
      half that in nontransgenic mice. The lipoprotein alterations are accompanied by
      up to a 5-fold increase in circulating nonesterified fatty acids, which may be
      the cause of fatty livers and increased liver triglyceride production also
      observed in the transgenic mice. These observations indicate that the primary
      defect leading to hypertriglyceridemia in apoC-III overexpressers is an impaired
      clearance of apoB48 remnants due to apoE insufficiency. Therefore, transgenic
      mice that overexpressed human apoE were cross-bred with the apoC-III
      overexpressers. Transgenic progeny that produced both human apoE and human apoC
      III had normal levels of plasma triglyceride and normal amounts of apoB48
      remnants. Thus, our studies suggest that a function of apoC-III is to modulate
      the apoE-mediated clearance of lipoproteins, and that the concentration of apoC
      III relative to apoE is a key determinant of triglyceride levels in plasma.

PMID- 8294491
TI  - Transcriptional and posttranscriptional mechanisms modulate creatine kinase
      expression during differentiation of osteoblastic cells.
AB  - Enhancement of energy metabolism is fundamental to the developmental programs of
      many cell types. This work examines the molecular mechanisms that mediate changes
      in energy metabolism during differentiation of osteoblastic cells. When the rat
      osteoblastic cell line, ROS 17/2.8, is induced to differentiate with 1,25
      dihydroxyvitamin D3, expression of creatine kinase-b (ck-b), a pivotal enzyme in
      energy metabolism, is enhanced. Maximum enhancement occurs at 48 h of induction
      with 10 nM 1,25-dihydroxyvitamin D3 when creatine kinase activity is 2.1-fold
      over uninduced cells. This is associated with a 2-fold increase in transcription
      rate and the formation of a second protein-DNA complex on the ck-b gene promoter
      that is supplementary to the one present in undifferentiated cells. In addition,
      the contribution of posttranscriptional regulatory mechanisms is suggested by (1)
      the increase in ck-b mRNA abundance exceeds that of transcription rate,
      indicating an increase in message stability, (2) the increase in ck-b mRNA
      precedes and exceeds that of protein activity, indicating translational
      modulation, and (3) RNA mobility-shift assays indicate that a cytosolic factor in
      ROS 17/2.8 cells interacts specifically with the highly conserved 3'-untranslated
      region of the ck-b mRNA. We have previously reported that such an interaction
      mediates translational control (Ch'ng, J. L. C., Shoemaker, D. L., Schimmel, P.,
      and Holmes, E.W. (1990) Science 248, 1003-1006). The physiological roles of these
      regulatory mechanisms during osteoblast differentiation are discussed.

PMID- 8294492
TI  - Alternative splicing of the NC1 domain of the human alpha 3(IV) collagen gene.
      Differential expression of mRNA transcripts that predict three protein variants
      with distinct carboxyl regions.
AB  - Three clones of NC1 of alpha 3(IV) collagen, named Q1, L5, and V, were isolated
      from human kidney; these predict three variant alpha 3(IV) NC1 domains of 232-,
      60-, and 199-amino acid residues, respectively, with unique COOH-termini. The
      human collagen IV gene (COL4A3) was isolated and characterized, and it was shown
      that the cDNA variants arose from alternative splicing by deletion of exon 4 in
      L5 and deletion of exon 2 in V. The mRNA transcripts were differentially
      expressed in fetal and adult human kidney with Q1 the major species. Exon 4-L5
      lacked 183 residues from the carboxyl terminus with a frameshift producing a
      unique 11-amino acid terminal peptide. In exon 2-V a frameshift resulted in a
      unique V carboxyl terminus of 53 novel peptides with a new glycosylation site.
      The size of recombinant proteins indicated the frameshifts and new stop codons
      were as predicted. The multiple forms of the alpha 3(IV) NC1 region may
      contribute to autoimmune glomerular disease and hereditary nephritis, in which
      this portion of the collagen IV molecule is thought to play an important role.

PMID- 8294493
TI  - Bcl-2 and the regulation of programmed cell death.

PMID- 8294494
TI  - A small rab GTPase is distributed in cytoplasmic vesicles in non polarized cells
      but colocalizes with the tight junction marker ZO-1 in polarized epithelial
      cells.
AB  - Small rab/Ypt1/Sec4 GTPase family have been involved in the regulation of
      membrane traffic along the biosynthetic and endocytic pathways in eucaryotic
      cells. Polarized epithelial cells have morphologically and functionally distinct
      apical and basolateral surfaces separated by tight junctions. The establishment
      and maintenance of these structures require delivery of membrane proteins and
      lipids to these domains. In this work, we have isolated a cDNA clone from a human
      intestinal cDNA library encoding a small GTPase, rab13, closely related to the
      yeast Sec4 protein. Confocal microscopy analysis on polarized Caco-2 cells shows
      that rab13 protein colocalized with the tight junction marker ZO-1. Cryostat
      sections of tissues confirm that rab13 localized to the junctional complex region
      of a variety of epithelia, including intestine, kidney, liver, and of endothelial
      cells. This localization requires assembly and integrity of the tight junctions.
      Disruption of tight junctions by incubation in low Ca2+ media induces the
      redistribution of rab13. In cells devoid of tight junctions, rab13 was found
      associated with vesicles dispersed throughout the cytoplasm. Cell-cell contacts
      initiated by E-cadherin in transfected L cells do not recruit rab13 to the
      resulting adherens-like junction complexes. The participation of rab13 in
      polarized transport, in the assembly and/or the activity of tight junctions is
      discussed.

PMID- 8294495
TI  - Biochemical and molecular characterization of the chicken cysteine-rich protein,
      a developmentally regulated LIM-domain protein that is associated with the actin
      cytoskeleton.
AB  - LIM domains are present in a number of proteins including transcription factors,
      a proto-oncogene product, and the adhesion plaque protein zyxin. The LIM domain
      exhibits a characteristic arrangement of cysteine and histidine residues and
      represents a novel zinc binding sequence (Michelsen et al., 1993). Previously, we
      reported the identification of a 23-kD protein that interacts with zyxin in vitro
      (Sadler et al., 1992). In this report, we describe the purification and
      characterization of this 23-kD zyxin-binding protein from avian smooth muscle.
      Isolation of a cDNA encoding the 23-kD protein has revealed that it consists of
      192 amino acids and exhibits two copies of the LIM motif. The 23-kD protein is
      91% identical to the human cysteine-rich protein (hCRP); therefore we refer to it
      as the chicken cysteine-rich protein (cCRP). Examination of a number of chick
      embryonic tissues by Western immunoblot analysis reveals that cCRP exhibits
      tissue-specific expression. cCRP is most prominent in tissues that are enriched
      in smooth muscle cells, such as gizzard, stomach, and intestine. In primary cell
      cultures derived from embryonic gizzard, differentiated smooth muscle cells
      exhibit the most striking staining with anti-cCRP antibodies. We have performed
      quantitative Western immunoblot analysis of cCRP, zyxin, and alpha-actinin levels
      during embryogenesis. By this approach, we have demonstrated that the expression
      of cCRP is developmentally regulated.

PMID- 8294496
TI  - In vivo phosphorylation of regulatory light chain of myosin II during mitosis of
      cultured cells.
AB  - Phosphorylation of the regulatory light chain of myosin II (MLC) controls the
      contractility of actomyosin in nonmuscle and muscle cells. It has been reported
      that cdc2 phosphorylates MLC in vitro at Ser-1 or Ser-2 and Thr-9 which protein
      kinase C phosphorylates (Satterwhite, L. L., M. J. Lohka, K. L. Wilson, T. Y.
      Scherson, L. K. Cisek, J. L. Corden, and T. D. Pollard. 1992 J. Cell Biol.
      118:595-605). We have examined in vivo phosphorylation of MLC during mitosis and
      after the release of mitotic arrest. Phosphate incorporation of MLC in mitotic
      cells is found to be 6-12 times greater than that in nonmitotic cells.
      Phosphopeptide maps have revealed that the MLC from mitotic cells is
      phosphorylated at Ser-1 and/or Ser-2 (Ser-1/2), but not at Thr-9. MLC is also
      phosphorylated to a much lesser extent at Ser-19 which myosin light chain kinase
      phosphorylates. On the other hand, MLC of nonmitotic cells is phosphorylated at
      Ser-19 but not at Ser-1/2. The extent of phosphate incorporation is doubled at 30
      min after the release of mitotic arrest when some cells start cytokinesis.
      Phosphopeptide analyses have revealed that the phosphorylation at Ser-19 is
      increased 20 times, while the phosphorylation at Ser-1/2 is decreased by half.
      This high extent of MLC phosphorylation at Ser-19 is maintained for another 30
      min and gradually decreased to near the level of interphase cells as cells
      complete spreading at 180 min. On the other hand, phosphorylation at Ser-1/2 is
      decreased to 18% at 60 min, and is practically undetectable at 180 min after the
      release of mitotic arrest. The stoichiometry of MLC phosphorylation has been
      determined by quantitation of phosphorylated and unphosphorylated forms of MLC
      separated on 2D gels. The molar ratio of phosphorylated MLC to total MLC is found
      to be 0.16 +/- 0.06 and 0.31 +/- 0.05 in interphase and mitotic cells,
      respectively. The ratio is increased to 0.49 +/- 0.05 at 30 min after the release
      of mitotic arrest. These results suggest that the change in the phosphorylation
      site from Ser-1/2 to Ser-19 plays an important role in signaling cytokinesis.

PMID- 8294497
TI  - Sodium channels aggregate at former synaptic sites in innervated and denervated
      regenerating muscles.
AB  - The role of innervation in the establishment and regulation of the synaptic
      density of voltage-activated Na channels (NaChs) was investigated at regenerating
      neuromuscular junctions. Rat muscles were induced to degenerate after injection
      of the Australian tiger snake toxin, notexin. The loose-patch voltage clamp
      technique was used to measure the density and distribution of NaChs on muscle
      fibers regenerating with or without innervation. In either case, new myofibers
      formed within the original basal lamina sheaths, and, NaChs became concentrated
      at regenerating endplates nearly as soon as they formed. The subsequent increase
      in synaptic NaCh density followed a time course similar to postnatal muscles.
      Neuromuscular endplates regenerating after denervation, with no nerve terminals
      present, had NaCh densities not significantly different from endplates
      regenerating in the presence of nerve terminals. The results show that the nerve
      terminal is not required for the development of an enriched NaCh density at
      regenerating neuromuscular synapses and implicate Schwann cells or basal lamina
      as the origin of the signal for NaCh aggregation. In contrast, the change in
      expression from the immature to the mature form of the NaCh isoform that normally
      accompanies development occurred only partially on muscles regenerating in the
      absence of innervation. This aspect of NaCh regulation is thus dependent upon
      innervation.

PMID- 8294498
TI  - Cerebroglycan: an integral membrane heparan sulfate proteoglycan that is unique
      to the developing nervous system and expressed specifically during neuronal
      differentiation.
AB  - Heparan sulfate proteoglycans (HSPGs) are found on the surface of all adherent
      cells and participate in the binding of growth factors, extracellular matrix
      glycoproteins, cell adhesion molecules, and proteases and antiproteases. We
      report here the cloning and pattern of expression of cerebroglycan, a
      glycosylphosphatidylinositol (GPI)-anchored HSPG that is found in the developing
      rat brain (previously referred to as HSPG M13; Herndon, M. E., and A. D. Lander.
      1990. Neuron. 4:949-961). The cerebroglycan core protein has a predicted
      molecular mass of 58.6 kD and five potential heparan sulfate attachment sites.
      Together with glypican (David, G., V. Lories, B. Decock, P. Marynen, J.-J.
      Cassiman, and H. Van den Berghe. 1990. J. Cell Biol. 111:3165-3176), it defines a
      family of integral membrane HSPGs characterized by GPI linkage and conserved
      structural motifs, including a pattern of 14 cysteine residues that is absolutely
      conserved. Unlike other known integral membrane HSPGs, including glypican and
      members of the syndecan family of transmembrane proteoglycans, cerebroglycan is
      expressed in only one tissue: the nervous system. In situ hybridization
      experiments at several developmental stages strongly suggest that cerebroglycan
      message is widely and transiently expressed by immature neurons, appearing around
      the time of final mitosis and disappearing after cell migration and axon
      outgrowth have been completed. These results suggest that cerebroglycan may
      fulfill a function related to the motile behaviors of developing neurons.

PMID- 8294499
TI  - Syndecan-1 expressed in Schwann cells causes morphological transformation and
      cytoskeletal reorganization and associates with actin during cell spreading.
AB  - To investigate the biological functions of transmembrane proteoglycans we have
      produced clonal cell lines of rat Schwann cells that express the hybrid
      proteoglycan syndecan-1. This was done by transfection of newborn rat Schwann
      cells with a plasmid vector bearing the rat syndecan-1 cDNA sequence under
      transcriptional control of the constitutively active cytomegalovirus promoter,
      and a neomycin resistance gene. Stably expressing cells were selected by growth
      in G418. Expression of syndecan-1 was verified by Northern and immunoblot
      analysis and immunoprecipitation of 35SO4-labeled proteoglycans. The syndecan-1
      expressing cells exhibited significantly enhanced spreading on several different
      substrata, including fibronectin and laminin, and an altered morphology. The
      enhanced spreading appeared to result from the presence of syndecan-1, based on
      the observation that anti-syndecan-1 antibodies inhibited the enhanced substratum
      spreading. There was also a reorganization of cytoskeletal structures and
      formation of focal adhesions, visualized by anti-vinculin staining, which were
      absent from control Schwann cells. There was no apparent stable association of
      cell surface syndecan-1 with focal contact sites, as determined by dual staining
      with anti-syndecan-1 and anti-vinculin antibodies. Colocalization of patches of
      cell surface syndecan-1 with actin was observed, but only during cell spreading.
      These findings provide evidence for a role of transmembrane proteoglycans in
      cellular morphogenesis, and suggest that transient association of syndecans with
      microfilaments may be an important aspect of their biological function.

PMID- 8294500
TI  - Latent transforming growth factor-beta 1 associates to fibroblast extracellular
      matrix via latent TGF-beta binding protein.
AB  - The role of latent transforming growth factor-beta (TGF-beta) binding protein
      (LTBP) in the association of TGF-beta 1 to the extracellular matrix of cultured
      fibroblasts and HT-1080 fibrosarcoma cells was studied by immunochemical methods.
      The matrices were isolated from the cells, and the levels of LTBP and TGF-beta 1
      were estimated by immunoblotting and immunoprecipitation. LTBP, TGF-beta 1, and
      its propeptide (latency-associated peptide, LAP) were found to associate to the
      extracellular matrix. Immunoblotting analysis indicated that treatment of the
      cells with plasmin resulted in a concomitant time and dose dependent release of
      both LTBP and TGF-beta 1 from the extracellular matrix to the supernatant.
      Comparison of molecular weights suggested that plasmin treatment resulted in the
      cleavage of LTBP from the high molecular weight fibroblast form to a form
      resembling the low molecular weight LTBP found in platelets. Pulse-chase and
      immunoprecipitation analysis indicated that both the free form of LTBP and LTBP
      complexed to latent TGF-beta were efficiently incorporated in the extracellular
      matrix, from where both complexes were slowly released to the culture medium.
      Addition of plasmin to the chase solution resulted, however, in a rapid release
      of LTBP from the matrix. Fibroblast derived LTBP was found to associate to the
      matrix of HT-1080 cells in a plasmin sensitive manner as shown by
      immunoprecipitation analysis. These results suggest that the latent form of TGF
      beta 1 associates with the extracellular matrix via LTBP, and that the release of
      latent TGF-beta 1 from the matrix is a consequence of proteolytic cleavage(s) of
      LTBP.

PMID- 8294501
TI  - Centrosome assembly in vitro: role of gamma-tubulin recruitment in Xenopus sperm
      aster formation.
AB  - Centrioles organize microtubules in two ways: either microtubules elongate from
      the centriole cylinder itself, forming a flagellum or a cilium ("template
      elongation"), or pericentriolar material assembles and nucleates a microtubule
      aster ("astral nucleation"). During spermatogenesis in most species, a motile
      flagellum elongates from one of the sperm centrioles, whereas after fertilization
      a large aster of microtubules forms around the sperm centrioles in the egg
      cytoplasm. Using Xenopus egg extracts we have developed an in vitro system to
      study this change in microtubule-organizing activity. An aster of microtubules
      forms around the centrioles of permeabilized frog sperm in egg extracts, but not
      in pure tubulin. However, when the sperm heads are incubated in the egg extract
      in the presence of nocodazole, they are able to nucleate a microtubule aster
      after isolation and incubation with pure calf brain tubulin. This provides a two
      step assay that distinguishes between centrosome assembly and subsequent
      microtubule nucleation. We have studied several centrosomal antigens during
      centrosome assembly. The CTR2611 antigen is present in the sperm head in the peri
      centriolar region. gamma-tubulin and certain phosphorylated epitopes appear in
      the centrosome only after incubation in the egg extract. gamma-tubulin is
      recruited from the egg extract and associated with electron-dense patches
      dispersed in a wide area around the centrioles. Immunodepletion of gamma-tubulin
      and associated molecules from the egg extract before sperm head incubation
      prevents the change in microtubule-organizing activity of the sperm heads. This
      suggests that gamma-tubulin and/or associated molecules play a key role in
      centrosome formation and activity.

PMID- 8294502
TI  - Deletions in the cytoplasmic domain of platelet-endothelial cell adhesion
      molecule-1 (PECAM-1, CD31) result in changes in ligand binding properties.
AB  - Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a member of the
      immunoglobulin superfamily present on platelets, endothelial cells, and
      leukocytes that may function as a vascular cell adhesion molecule. The purpose of
      this study was to examine the role of the cytoplasmic domain in PECAM-1 function.
      To accomplish this, wild-type and mutated forms of PECAM-1 cDNA were transfected
      into murine fibroblasts and the functional characteristics of the cells analyzed.
      Wild-type PECAM-1 localized to the cell-cell borders of adjacently transfected
      cells and mediated heterophilic, calcium-dependent L-cell aggregation that was
      inhibitable by a polyclonal and two monoclonal anti-PECAM-1 antibodies. A mutant
      protein lacking the entire cytoplasmic domain did not support aggregation or move
      to cell-cell borders. In contrast, both forms of PECAM-1 with partially truncated
      cytoplasmic domains (missing either the COOH-terminal third or two thirds of the
      cytoplasmic domain) localized to cell-cell borders in 3T3 cells in a manner
      analogous to the distribution seen in cultured endothelial cells. L-cells
      expressing these mutants demonstrated homophilic, calcium-independent aggregation
      that was blocked by the polyclonal anti-PECAM-1 antibody, but not by the two
      bioactive monoclonal antibodies. Although changes in the cytoplasmic domain of
      other receptors have been shown to alter ligand-binding affinity, to our
      knowledge, PECAM-1 is the first example of a cell adhesion molecule where changes
      in the cytoplasmic domain result in a switch in the basic mechanism of adhesion
      leading to different ligand-binding specificity. Variations in the cytoplasmic
      domain could thus be a potential mechanism for regulating PECAM-1 activity in
      vivo.

PMID- 8294504
TI  - Differential trafficking of soluble and integral membrane secretory granule
      associated proteins.
AB  - The posttranslational processing enzyme peptidylglycine alpha-amidating
      monooxygenase (PAM) occurs naturally in integral membrane and soluble forms. With
      the goal of understanding the targeting of these proteins to secretory granules,
      we have compared the maturation, processing, secretion, and storage of PAM
      proteins in stably transfected AtT-20 cells. Integral membrane and soluble PAM
      proteins exit the ER and reach the Golgi apparatus with similar kinetics.
      Biosynthetic labeling experiments demonstrated that soluble PAM proteins were
      endoproteolytically processed to a greater extent than integral membrane PAM;
      this processing occurred in the regulated secretory pathway and was blocked by
      incubation of cells at 20 degrees C. 16 h after a biosynthetic pulse, a larger
      proportion of soluble PAM proteins remained cell-associated compared with
      integral membrane PAM, suggesting that soluble PAM proteins were more efficiently
      targeted to storage granules. The nonstimulated secretion of soluble PAM proteins
      peaked 1-2 h after a biosynthetic pulse, suggesting that release was from
      vesicles which bud from immature granules during the maturation process. In
      contrast, soluble PAM proteins derived through endoproteolytic cleavage of
      integral membrane PAM were secreted in highest amount during later times of
      chase. Furthermore, immunoprecipitation of cell surface-associated integral
      membrane PAM demonstrated that very little integral membrane PAM reached the cell
      surface during early times of chase. However, when a truncated PAM protein
      lacking the cytoplasmic tail was expressed in AtT-20 cells, > 50% of the
      truncated PAM-1 protein reached the cell surface within 3 h. We conclude that the
      trafficking of integral membrane and soluble secretory granule-associated enzymes
      differs, and that integral membrane PAM proteins are less efficiently retained in
      maturing secretory granules.

PMID- 8294503
TI  - Replacement of the phospholipid-anchor in the contact site A glycoprotein of D.
      discoideum by a transmembrane region does not impede cell adhesion but reduces
      residence time on the cell surface.
AB  - The contact site A (csA) glycoprotein of Dictyostelium discoideum, a cell
      adhesion molecule expressed in aggregating cells, is inserted into the plasma
      membrane by a ceramide-based phospholipid (PL) anchor. A carboxyterminal sequence
      of 25 amino acids of the primary csA translation product proved to contain the
      signal required for PL modification. CsA is known to be responsible for rapid,
      EDTA-resistant cohesion of cells in agitated suspensions. To investigate the role
      of the PL modification of this protein, the anchor was replaced by the
      transmembrane region and short cytoplasmic tail of another plasma membrane
      protein of D. discoideum. In cells transformed with appropriate vectors, PL
      anchored or transmembrane csA was expressed under the control of an actin
      promoter during growth and development. The transmembrane form enabled the cells
      to agglutinate in the presence of shear forces, similar to the PL-anchored wild
      type form. However, the transmembrane form was much more rapidly internalized and
      degraded. In comparison to other cell-surface glycoproteins of D. discoideum the
      internalization rate of the PL-anchored csA was extremely slow, most likely
      because of its exclusion from the clathrin-mediated pathway of pinocytosis. Thus,
      our results indicate that the phospholipid modification is not essential for the
      csA-mediated fast type of cell adhesion but guarantees long persistence of the
      protein on the cell surface.

PMID- 8294505
TI  - Redistribution of a rab3-like GTP-binding protein from secretory granules to the
      Golgi complex in pancreatic acinar cells during regulated exocytosis.
AB  - Regulated secretion from pancreatic acinar cells occurs by exocytosis of zymogen
      granules (ZG) at the apical plasmalemma. ZGs originate from the TGN and undergo
      prolonged maturation and condensation. After exocytosis, the zymogen granule
      membrane (ZGM) is retrieved from the plasma membrane and ultimately reaches the
      TGN. In this study, we analyzed the fate of a low M(r) GTP-binding protein during
      induced exocytosis and membrane retrieval using immunoblots as well as light and
      electron microscopic immunocytochemistry. This 27-kD protein, identified by a
      monoclonal antibody that recognizes rab3A and B, may be a novel rab3 isoform. In
      resting acinar cells, the rab3-like protein was detected primarily on the
      cytoplasmic face of ZGs, with little labeling of the Golgi complex and no
      significant labeling of the apical plasmalemma or any other intracellular
      membranes. Stimulation of pancreatic lobules in vitro by carbamylcholine for 15
      min, resulted in massive exocytosis that led to a near doubling of the area of
      the apical plasma membrane. However, no relocation of the rab3-like protein to
      the apical plasmalemma was seen. After 3 h of induced exocytosis, during which
      time approximately 90% of the ZGs is released, the rab3-like protein appeared to
      translocate to small vesicles and newly forming secretory granules in the TGN. No
      significant increase of the rab3-like protein was found in the cytosolic fraction
      at any time during stimulation. Since the protein is not detected on the apical
      plasmalemma after stimulation, we conclude that recycling may involve a membrane
      dissociation-association cycle that accompanies regulated exocytosis.

PMID- 8294506
TI  - Characterization of the budding compartment of mouse hepatitis virus: evidence
      that transport from the RER to the Golgi complex requires only one vesicular
      transport step.
AB  - Mouse hepatitis coronavirus (MHV) buds into pleomorphic membrane structures with
      features expected of the intermediate compartment between the ER and the Golgi
      complex. Here, we characterize the MHV budding compartment in more detail in
      mouse L cells using streptolysin O (SLO) permeabilization which allowed us to
      better visualize the membrane structures at the ER-Golgi boundary. The MHV
      budding compartment shares membrane continuities with the rough ER as well as
      with cisternal elements on one side of the Golgi stack. It also labeled with p58
      and rab2, two markers of the intermediate compartment, and with PDI, usually
      considered to be a marker of the rough ER. The membranes of the budding
      compartment, as well as the budding virions themselves, but not the rough ER,
      labeled with the N-acetyl-galactosamine (GalNAc)-specific lectin Helix pomatia.
      When the SLO-permeabilized cells were treated with guanosine 5'-(3-O
      thio)triphosphate (GTP gamma S), the budding compartment accumulated a large
      number of beta-cop-containing buds and vesicular profiles. Complementary
      biochemical experiments were carried out to determine whether vesicular transport
      was required for the newly synthesized M protein, that contains only O-linked
      oligosaccharides, to acquire first, GalNAc and second, the Golgi modifications
      galactose and sialic acid. The results from both in vivo studies and from the use
      of SLO-permeabilized cells showed that, while GalNAc addition occurred under
      conditions which block vesicular transport, both cytosol and ATP were
      prerequisites for the M protein oligosaccharides to acquire Golgi modifications.
      Collectively, our data argue that transport from the rough ER to the Golgi
      complex requires only one vesicular transport step and that the intermediate
      compartment is a specialized domain of the endoplasmatic reticulum that extends
      to the first cisterna on the cis side of the Golgi stack.

PMID- 8294507
TI  - Cytoplasmic retention of Xenopus nuclear factor 7 before the mid blastula
      transition uses a unique anchoring mechanism involving a retention domain and
      several phosphorylation sites.
AB  - Xenopus nuclear factor 7 (xnf7) is a maternally expressed protein that belongs to
      the B-box zinc finger gene family consisting of transcription factors,
      protooncogenes, and ribonucleoproteins. Its function is regulated by retention in
      the cytoplasm from oocyte maturation until the mid blastula transition (MBT) when
      it reenters the nucleus. We defined a 22-amino acid cytoplasmic retention domain
      (CRD) in xnf7 that functioned cooperatively with two phosphorylation sites within
      the xnf7 molecule to retain the protein in the cytoplasm until the MBT. Deletion
      of this region or mutations in the phosphorylation sites resulted in the early
      entry of xnf7 into the nucleus. A mutation changing one of the phosphorylation
      sites to a glutamic acid resulted in the prolonged retention of the xnf7 protein
      in the cytoplasm until stages 9-10, well past the MBT. Additionally, a mutant
      form of xnf7 possessing a second nuclear localization signal at the COOH terminus
      was retained in the cytoplasm. This suggests that retention of xnf7 was not due
      to the masking of its NLS as is the case with NFkB and dorsal but was due to a
      novel anchoring mechanism in which the CRD interacts with an anchor protein. The
      CRD sequence is also found in another B-box zinc finger protein that is also
      retained in the cytoplasm until the MBT in the newt. Therefore, we believe that
      this may be an important mechanism whereby the function of a number of nuclear
      proteins is regulated during development.

PMID- 8294508
TI  - Motile kinetochores and polar ejection forces dictate chromosome position on the
      vertebrate mitotic spindle.
AB  - We argue that hypotheses for how chromosomes achieve a metaphase alignment, that
      are based solely on a tug-of-war between poleward pulling forces produced along
      the length of opposing kinetochore fibers, are no longer tenable for vertebrates.
      Instead, kinetochores move themselves and their attached chromosomes, poleward
      and away from the pole, on the ends of relatively stationary but
      shortening/elongating kinetochore fiber microtubules. Kinetochores are also
      "smart" in that they switch between persistent constant-velocity phases of
      poleward and away from the pole motion, both autonomously and in response to
      information within the spindle. Several molecular mechanisms may contribute to
      this directional instability including kinetochore-associated microtubule motors
      and kinetochore microtubule dynamic instability. The control of kinetochore
      directional instability, to allow for congression and anaphase, is likely
      mediated by a vectorial mechanism whose magnitude and orientation depend on the
      density and orientation or growth of polar microtubules. Polar microtubule arrays
      have been shown to resist chromosome poleward motion and to push chromosomes away
      from the pole. These "polar ejection forces" appear to play a key role in
      regulating kinetochore directional instability, and hence, positions achieved by
      chromosomes on the spindle.

PMID- 8294509
TI  - Nuclear assembly with lambda DNA in fractionated Xenopus egg extracts: an
      unexpected role for glycogen in formation of a higher order chromatin
      intermediate.
AB  - Crude extracts of Xenopus eggs are capable of nuclear assembly around chromatin
      templates or even around protein-free, naked DNA templates. Here the requirements
      for nuclear assembly around a naked DNA template were investigated. Extracts were
      separated by ultracentrifugation into cytosol, membrane, and gelatinous pellet
      fractions. It was found that, in addition to the cytosolic and membrane
      fractions, a component of the gelatinous pellet fraction was required for the
      assembly of functional nuclei around a naked DNA template. In the absence of this
      component, membrane-bound but functionally inert spheres of lambda DNA were
      formed. Purification of the active pellet factor unexpectedly demonstrated the
      component to be glycogen. The assembly of functionally active nuclei, as assayed
      by DNA replication and nuclear transport, required that glycogen be pre-incubated
      with the lambda DNA and cytosol during the period of chromatin and higher order
      intermediate formation, before the addition of membranes. Hydrolysis of glycogen
      with alpha-amylase in the extract blocked nuclear formation. Upon analysis,
      chromatin formed in the presence of cytosol and glycogen alone appeared highly
      condensed, reminiscent of the nuclear assembly intermediate described by Newport
      in crude extracts (Newport, J. 1987. Cell. 48:205-217). In contrast, chromatin
      formed from phage lambda DNA in cytosol lacking glycogen formed "fluffy chromatin
      like" structures. Using sucrose gradient centrifugation, the highly condensed
      intermediates formed in the presence of glycogen could be isolated and were now
      able to serve as nuclear assembly templates in extracts lacking glycogen, arguing
      that the requirement for glycogen is temporally restricted to the time of
      intermediate formation and function. Glycogen does not act simply by inducing
      condensation of the chromatin, since similarly isolated mitotically condensed
      chromatin intermediates do not form functional nuclei. However, both mitotic and
      fluffy interphase chromatin intermediates formed in the absence of glycogen can
      be rescued to form functional nuclei when added to a second extract which
      contains glycogen. This study presents a novel role for a carbohydrate in nuclear
      assembly, a role which involves the formation of a particular chromatin
      intermediate. Potential models for the role of glycogen are discussed.

PMID- 8294511
TI  - A 69-kD protein that associates reversibly with the Sm core domain of several
      spliceosomal snRNP species.
AB  - The biogenesis of the spliceosomal small nuclear ribonucleoproteins (snRNPs) U1,
      U2, U4, and U5 involves: (a) migration of the snRNA molecules from the nucleus to
      the cytoplasm; (b) assembly of a group of common proteins (Sm proteins) and their
      binding to a region on the snRNAs called the Sm-binding site; and (c)
      translocation of the RNP back to the nucleus. A first prerequisite for
      understanding the assembly pathway and nuclear transport of the snRNPs in more
      detail is the knowledge of all the snRNP proteins that play essential roles in
      these processes. We have recently observed a previously undetected 69-kD protein
      in 12S U1 snRNPs isolated from HeLa nuclear extracts under non-denaturing
      conditions that is clearly distinct from the U1-70K protein. The following
      evidence indicates that the 69-kD protein is a common, rather than a U1-specific,
      protein, possibly associating with the snRNP core particles by protein-protein
      interaction. (a) Antibodies raised against the 69-kD protein, which did not cross
      react with any of the Sm proteins B'-G, precipitated not only U1 snRNPs, but also
      the other spliceosomal snRNPs U2, U4/U6 and U5, albeit to a lower extent. (b) U1,
      U2, and U5 core RNP particles reconstituted in vitro contain the 69-kD protein.
      (c) Xenopus laevis oocytes contain an immunologically related homologue of the
      human 69-kD protein. When U1 snRNA as well as a mutant U1 snRNA, that can bind
      the Sm core proteins but lacks the capacity to bind the U1-specific proteins 70K,
      A, and C, were injected into Xenopus oocytes to allow assembly in vivo, they were
      recognized by antibodies specific against the 69-kD protein in the ooplasm and in
      the nucleus. The 69-kD protein is under-represented, if present at all, in
      purified 17S U2 and in 25S [U4/U6.U5] tri-snRNPs, isolated from HeLa nuclear
      extracts. Our results are consistent with the working hypothesis that this
      protein may either play a role in the cytoplasmic assembly of the core domain of
      the snRNPs and/or in the nuclear transport of the snRNPs. After transport of the
      snRNPs into the nucleus, it may dissociate from the particles as for example in
      the case of the 17S U2 or the 25S [U4/U6.U5] tri-snRNP, which bind more than 10
      different snRNP specific proteins each in the nucleus.

PMID- 8294510
TI  - Disruption of pre-mRNA splicing in vivo results in reorganization of splicing
      factors.
AB  - We have examined the functional significance of the organization of pre-mRNA
      splicing factors in a speckled distribution in the mammalian cell nucleus. Upon
      microinjection into living cells of oligonucleotides or antibodies that inhibit
      pre-mRNA splicing in vitro, we observed major changes in the organization of
      splicing factors in vivo. Interchromatin granule clusters became uniform in
      shape, decreased in number, and increased in both size and content of splicing
      factors, as measured by immunofluorescence. These changes were transient and the
      organization of splicing factors returned to their normal distribution by 24 h
      following microinjection. Microinjection of these oligonucleotides or antibodies
      also resulted in a reduction of transcription in vivo, but the oligonucleotides
      did not inhibit transcription in vitro. Control oligonucleotides did not disrupt
      splicing or transcription in vivo. We propose that the reorganization of splicing
      factors we observed is the result of the inhibition of splicing in vivo.

PMID- 8294512
TI  - A phosphatidylinositol transfer protein controls the phosphatidylcholine content
      of yeast Golgi membranes.
AB  - SEC14p is required for protein transport from the yeast Golgi complex. We
      describe a quantitative analysis of yeast bulk membrane and Golgi membrane
      phospholipid composition under conditions where Golgi secretory function has been
      uncoupled from its usual SEC14p requirement. The data demonstrate that SEC14p
      specifically functions to maintain a reduced phosphatidylcholine content in Golgi
      membranes and indicate that overproduction of SEC14p markedly reduces the
      apparent rate of phosphatidylcholine biosynthesis via the CDP-choline pathway in
      vivo. We suggest that SEC14p serves as a sensor of Golgi membrane phospholipid
      composition through which the activity of the CDP-choline pathway in Golgi
      membranes is regulated such that a phosphatidylcholine content that is compatible
      with the essential secretory function of these membranes is maintained.

PMID- 8294513
TI  - Expression of a dominant allele of human ARF1 inhibits membrane traffic in vivo.
AB  - ADP-ribosylation factor (ARF) proteins and inhibitory peptides derived from ARFs
      have demonstrated activities in a number of in vitro assays that measure ER-to
      Golgi and intra-Golgi transport and endosome fusion. To better understand the
      roles of ARF proteins in vivo, stable cell lines were obtained from normal rat
      kidney (NRK) cells transfected with either wild-type or a dominant activating
      allele ([Q71L]) of the human ARF1 gene under the control of the interferon
      inducible mouse Mx1 promoter. Upon addition of interferon, expression of ARF1
      proteins increased with a half-time of 7-8 h, as determined by immunoblot
      analysis. Induction of mutant ARF1, but not wild-type ARF1, led to an inhibition
      of protein secretion with kinetics similar to that observed for induction of
      protein expression. Examination of the Golgi apparatus and the ER by indirect
      immunofluorescence or transmission electron microscopy revealed that expression
      of low levels of mutant ARF1 protein correlated with a dramatic increase in
      vesiculation of the Golgi apparatus and expansion of the ER lumen, while
      expression of substantially higher levels of wild-type ARF1 had no discernible
      effect. Endocytosis was also inhibited by expression of mutant ARF1, but not by
      the wild-type protein. Finally, the expression of [Q71L]ARF1, but not wild-type
      ARF1, antagonized the actions of brefeldin A, as determined by the delayed loss
      of ARF and beta-COP from Golgi membranes and disruption of the Golgi apparatus.
      General models for the actions of ARF1 in membrane traffic events are discussed.

PMID- 8294514
TI  - Protein kinase C activators inhibit receptor-mediated potocytosis by preventing
      internalization of caveolae.
AB  - Potocytosis is an endocytic pathway that utilizes glycosylphosphatidylinositol
      anchored membrane proteins and caveolae to concentrate and internalize small
      molecules. We now report that activators of protein kinase C are potent
      inhibitors of potocytosis. Activators such as phorbol-12-myristate-13-acetate
      (PMA) inhibit the internalization of receptors for 5-methyltetrahydrofolate but
      allow the internal receptor pool to return to the cell surface. PMA does not
      affect the clustering of the folate receptor but instead markedly reduces the
      number of caveolae. Exposure to PMA totally blocks the intracellular accumulation
      of 5-methyltetrahydrofolate without affecting receptor-independent uptake or the
      formation of polyglutamylated species of 5-methyltetrahydrofolate in the
      cytoplasm. These data suggest that PMA inhibits uptake by inactivating caveolae
      internalization.

PMID- 8294515
TI  - The unconventional myosin, Myo2p, is a calmodulin target at sites of cell growth
      in Saccharomyces cerevisiae.
AB  - Myo2p is an unconventional myosin required for polarized growth in Saccharomyces
      cerevisiae. Four lines of evidence suggest that (a) Myo2p is a target of
      calmodulin at sites of cell growth, and (b) the interaction between Myo2p and
      calmodulin is Ca2+ independent. First, as assessed by indirect
      immunofluorescence, the distributions of Myo2p and calmodulin are nearly
      indistinguishable throughout the cell cycle. Second, a genetic analysis indicates
      that mutations in CMD1 show allele-specific synthetic lethality with the myo2-66
      conditional mutation. Mutations that inactivate the Ca(2+)-binding sites of
      calmodulin have little or no effect on strains carrying myo2-66, whereas an
      allele with a mutation outside the Ca(2+)-binding sites dramatically increases
      the severity of the phenotype conferred by myo2-66. Third, Myo2p
      coimmunoprecipitates with calmodulin in the presence of Ca2+ or EGTA. Finally, we
      used a modified gel overlay assay to demonstrate direct interaction between
      calmodulin and fusion proteins containing portions of Myo2p. Calmodulin binds
      specifically to the region of Myo2p containing six tandem repeats of a motif
      called an IQ site. Binding occurs in either Ca2+ or EGTA, and only two sites are
      required to observe binding.

PMID- 8294516
TI  - The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin
      binding domains with bundling activity.
AB  - The myristoylated form of c-Abl protein, as well as the P210bcr/abl protein, have
      been shown by indirect immunofluorescence to associate with F-actin stress fibers
      in fibroblasts. Analysis of deletion mutants of c-Abl stably expressed in
      fibroblasts maps the domain responsible for this interaction to the extreme COOH
      terminus of Abl. This domain mediates the association of a heterologous protein
      with F-actin filaments after microinjection into NIH 3T3 cells, and directly
      binds to F-actin in a cosedimentation assay. Microinjection and cosedimentation
      assays localize the actin-binding domain to a 58 amino acid region, including a
      charged motif at the extreme COOH-terminus that is important for efficient
      binding. F-actin binding by Abl is calcium independent, and Abl competes with
      gelsolin for binding to F-actin. In addition to the F-actin binding domain, the
      COOH-terminus of Abl contains a proline-rich region that mediates binding and
      sequestration of G-actin, and the Abl F- and G-actin binding domains cooperate to
      bundle F-actin filaments in vitro. The COOH terminus of Abl thus confers several
      novel localizing functions upon the protein, including actin binding, nuclear
      localization, and DNA binding. Abl may modify and receive signals from the F
      actin cytoskeleton in vivo, and is an ideal candidate to mediate signal
      transduction from the cell surface and cytoskeleton to the nucleus.

PMID- 8294517
TI  - Three-dimensional structure of a single filament in the Limulus acrosomal bundle:
      scruin binds to homologous helix-loop-beta motifs in actin.
AB  - Frozen, hydrated acrosomal bundles from Limulus sperm were imaged with a 400 kV
      electron cryomicroscope. Segments of this long bundle can be studied as a P1
      crystal with a unit cell containing an acrosomal filament with 28 actin and 28
      scruin molecules in 13 helical turns. A novel computational procedure was
      developed to extract single columns of superimposed acrosomal filaments from the
      distinctive crystallographic view. Helical reconstruction was used to generate a
      three-dimensional structure of this computationally isolated acrosomal filament.
      The scruin molecule is organized into two domains which contact two actin
      subunits in different strands of the same actin filament. A correlation of
      Holmes' actin filament model to the density in our acrosomal filament map shows
      that actin subdomains 1, 2, and 3 match the model density closely. However, actin
      subdomain 4 matches rather poorly, suggesting that interactions with scruin may
      have altered actin conformation. Scruin makes extensive interactions with helix
      loop-beta motifs in subdomain 3 of one actin subunit and in subdomain 1 of a
      consecutive actin subunit along the genetic filament helix. These two actin
      subdomains are structurally homologous and are closely spaced along the actin
      filament. Our model suggests that scruin, which is derived from a tandemly
      duplicated gene, has evolved to bind structurally homologous but non-identical
      positions across two consecutive actin subunits.

PMID- 8294518
TI  - HIV-1 transactivator protein Tat induces proliferation and TGF beta expression in
      human articular chondrocytes.
AB  - The human immunodeficiency virus-1 (HIV-1) protein Tat binds to cell surface
      antigens and can regulate cellular responses. Tat has similar immunosuppressive
      effects as transforming growth factor-beta (TGF beta) and both inhibit lymphocyte
      proliferation. TGF beta is expressed by primary human articular chondrocytes and
      is their most potent growth factor. The present study analyzed the interactions
      of TGF beta and HIV Tat in the regulation of human articular chondrocytes.
      Synthetic or recombinant full-length Tat (1-86) induced chondrocyte proliferation
      and this was of similar magnitude as the response to TGF beta. Tat peptides that
      did not contain the RGD motif had similar chondrocyte stimulatory activity as
      full-length Tat. Among a series of Tat peptides, peptide 38-62 which contains the
      basic domain was the only one active, suggesting that this region is responsible
      for the effects on chondrocyte proliferation. Full-length Tat and peptide 38-62
      synergized with TGF beta and induced proliferative responses that were greater
      than those obtained with any combination of the known chondrocyte growth factors.
      Further characterization of the interactions between Tat and TGF beta showed that
      Tat increased synthesis and TGF beta activity and TGF beta 1 mRNA levels. The
      stimulatory effects of Tat and peptide 38-62 on chondrocyte proliferation were
      reduced by neutralizing antibodies to TGF beta and by TGF beta antisense
      oligonucleotides. These results identify a virally encoded protein and a
      synthetic peptide derived from it as novel and potent chondrocyte growth stimuli
      which act at least in part through the induction of TGF beta.

PMID- 8294520
TI  - Annotation: children in situations of political violence.

PMID- 8294519
TI  - Human laminin M chain (merosin): complete primary structure, chromosomal
      assignment, and expression of the M and A chain in human fetal tissues.
AB  - The primary structure of the human laminin M chain was determined from cDNA
      clones isolated from human placental libraries. The clones covered a total of
      6,942 bp, with 49-bp encoding a 5' end untranslated region and 6,893-bp coding
      for a translated sequence. The complete human laminin M chain contains a 22
      residue signal peptide and 3,088 residues of the mature M chain. The M chain has
      a domain structure similar to that of the human and mouse A chains. The homology
      between the two human laminin heavy chains is highest in the short arm region and
      lowest in the long arm helical domain I + II. Northern blot analysis of human
      fetal tissues showed that the M chain was expressed in most tissues such as
      cardiac muscle, pancreas, lung, spleen, kidney, adrenal gland, skin, testis,
      meninges, choroid plexus, and some other regions of the brain, but not in liver,
      thymus, and bone. In situ hybridization localized the expression of the M chain
      gene to cells of mesenchymal origin. In contrast, expression of the A chain was
      observed only in kidney, testis, neuroretina and some region of brain as
      determined by Northern analyses. Epithelial and endothelial cells were negative
      for both M and A chain gene transcripts. The gene for the human M chain (LAMM)
      was localized to chromosome 6q22-->23.

PMID- 8294521
TI  - Practitioner review: problems in children's peer relations: what can the
      clinician do?
AB  - This paper describes the assessment and treatment of children with peer
      relationship problems. The first part of the paper is organized around five
      topics: peer rejection, peer neglect, the absence of friendships, reputation in
      the peer group, and peer group affiliations. Next, a series of assessment methods
      is delineated, including peer, teacher, parent and self reports, as well as
      direct observational procedures. Finally, we suggest a number of treatment
      options, including social skills training, social cognitive interventions, and co
      operative group interventions.

PMID- 8294522
TI  - The epidemiology of Asperger syndrome. A total population study.
AB  - This paper describes a total population study of Asperger syndrome using a two
      stage procedure. All school children in an outer Goteborg borough were screened.
      Final case selection based on clinical work-up showed a minimum prevalence of 3.6
      per 1.000 children (7-16 years of age) using Gillberg and Gillberg's criteria and
      a male to female ratio of 4:1. Including suspected and possible Asperger syndrome
      cases, the prevalence rose to 7.1 per 1.000 children and the male:female ratio
      dropped to 2.3:1. These findings are discussed as they relate to previously
      published results in the field and to findings obtained using Szatmari et al.'s
      and ICD-10 draft criteria for the disorder.

PMID- 8294523
TI  - Why do autistic individuals show superior performance on the block design task?
AB  - Systematic variations of the block design task were given to 20 autistic, 33
      normal and 12 mildly retarded subjects. Designs were contrasted which were either
      "whole" or segmented, rotated or unrotated, and which did or did not contain
      obliques. Only segmentation, but neither of the spatial orientation factors,
      revealed a significant group difference. Autistic subjects, regardless of age and
      ability, performed better than controls when presented with unsegmented designs.
      This result suggests that they need less of the normally required effort to
      segment a gestalt, and thus supports the hypothesis of weak central coherence as
      a characteristic of information processing in autism.

PMID- 8294524
TI  - Bottle, tulip and wineglass: semantic and structural picture processing by savant
      artists.
AB  - Semantic and structural aspects of picture processing were investigated with
      graphically gifted mentally handicapped subjects and intellectually normal
      children. The results suggest that savants as well as controls rely primarily on
      semantically organised memory schemata when reproducing pictures. A semantically
      determined strategy also determines picture sorting. The findings indicate that
      within the domain of expertise there appears to be no difference between savants
      and normals regarding the nature of the mental structures underlying specific
      talents. The mental structures on which such talents are based, should therefore
      be regarded as being relatively independent of the level of general cognitive
      functioning.

PMID- 8294525
TI  - Genetic and environmental influences on depressive symptomatology in adolescence:
      individual differences and extreme scores.
AB  - The purpose of the current investigation was to compare the genetic and
      environmental influences on individual differences in depressive symptomatology
      (as assessed using the Children's Depression Inventory) to such influences on
      extreme scores in an unselected sample of adolescents. The sample included 707
      pairs of siblings (average ages 14.5 and 12.9 years, respectively) participating
      in a combined twin- and step-family study. Moderate genetic influence was found
      for the full range of individual differences in depression; in contrast, there
      was nonsignificant genetic influence, and significant shared environmental
      influence, on extreme scores. The results were interpreted using a risk model in
      which familial influences specific to the high end of the distribution contribute
      to depressive symptomatology in adolescence.

PMID- 8294526
TI  - Self-image as a predictor of outcome in adolescent major depressive disorder.
AB  - We investigated the ability of a measure of self-image, two measures of
      depression, and demographic characteristics to predict the outcome of depressive
      symptoms. Subjects were 47 adolescents who were referred to outpatient treatment
      for depression. Subjects were assessed for depressive symptoms at three time
      periods. Self-image as measured by the Offer Self-image Questionnaire (OSIQ) was
      a significant predictor of depressive symptoms at both 3 months and 1 year. That
      was independent of initial levels of depression. The two most predictive scales
      from the OSIQ were the emotional tone and mastery of the external world scales.
      The results are consistent with previous research indicating the importance of
      self-image in adolescent depression. The implications of these findings for
      treatment of adolescent depression are discussed.

PMID- 8294527
TI  - Temperament and major depression in 11 to 16 year olds.
AB  - Temperament (EAS teacher and parent questionnaire) and mental state (modified
      DISC-C interview with adolescent) was systematically assessed in 193 11 to 16
      year olds (112 girls, 81 boys) screened for major depression in the community.
      Sex differences in the structure of temperament were noted from both parent and
      teacher reports. High (negative) emotionality alone was associated with major
      depression, particularly (but not exclusively) in girls.

PMID- 8294528
TI  - The impact of anger between adults on siblings' emotions and social behavior.
AB  - Peer and sibling dyads (older children = 5-7 years; younger children = 2-5 years)
      were presented with simulations of friendly, angry, and resolution interactions
      between a male adult and the mother in the context of play sessions. Expressions
      of positive effect increased among female siblings during the anger period and
      continued to be more common in the resolution period than in other groups.
      Prosocial behavior among male siblings greatly increased in the resolution
      period, with siblings generally more prosocial towards each other than peers in
      this period. The findings suggest that siblings may attempt to buffer each other
      from the stress of exposure to adults' discord.

PMID- 8294529
TI  - Sociometric status and social behaviour of children with and without learning
      difficulties.
AB  - The sociometric status and behaviour of 179 children aged 8.0-12.0 years,
      including 36 children with learning disabilities, were examined. Compared to non
      LD children, more LD children were rejected and fewer were popular. LD children
      were nominated as shy, seeking help and as victims of bullying significantly more
      than non-LD children; fewer were nominated as cooperative or as a leader.
      Aggressive behaviours did not distinguish the two groups. Teacher scores of LD
      children's behaviour were not related to peer nominations, although those of non
      LD children were. Findings are discussed in relation to the role of social
      cognitive deficits in LD children's relationships with peers.

PMID- 8294530
TI  - Psychological testing on schoolchildren before and after pollution of drinking
      water in North Cornwall.
AB  - The tap water supply in Camelford, North Cornwall and environs was contaminated
      by aluminium and other metals in 1988. Richmond tests were routinely given before
      and after the pollution and here scores are compared between 39 children from
      schools in the contaminated area and 64 children from Cornish schools outside the
      polluted area. The study was retrospective and it was not possible to determine
      whether or how much polluted water individuals had consumed. No differences were
      found between groups either before or after the pollution accident nor was there
      any evidence for any sub-group of the polluted group which had been affected. The
      limits of conclusions which can be drawn from data available are discussed.

PMID- 8294531
TI  - Interviewing deaf children, the interviewer effect: a research note.
AB  - A highly structured diagnostic interview, the Child Assessment Schedule (CAS),
      was used to investigate the influence of the interviewer's signing ability and
      cultural status on the outcome of psychiatric assessments of signing deaf
      children and adolescents. Preliminary findings suggest that linguistic competence
      of the interviewer had a significant effect on the range of symptoms elicited at
      interview. In particular that poor competence leads to the masking of a child's
      emotional difficulties.

PMID- 8294532
TI  - Children's adjustment after parental separation: teacher, peer and self-report in
      a Greek sample: a research note.
AB  - The purpose of this study was to assess the psychosocial and academic competence
      of children from divorced families in Greece and to compare it with findings in
      other countries. The sample of the study consisted of fifth and sixth grade
      elementary school pupils (mean age = 11.3) attending Greek public schools. The
      "divorced family" group consisted of 26 children, while the control group
      consisted of all classmates of these students (N = 381) from intact families.
      Teacher, peer and self-rating instruments were used. Children from divorced
      families were found to experience serious difficulties in various aspects of
      their behavior and competence.

PMID- 8294533
TI  - Simultaneous determination of bile acids in rat bile and serum by high
      performance liquid chromatography.
AB  - A method for the simultaneous determination of bile acids in rat bile and serum
      by high-performance liquid chromatography with a post-column enzymic reaction and
      fluorescence detection has been developed. Without prior fractionation and
      alkaline hydrolysis, 26 unconjugated, glycine- and taurine-conjugated bile acids
      were determined. They were separated on a reversed-phase column using a linear
      gradient solvent system of 200 mM dibasic ammonium phosphate buffer (pH 7.9)
      acetonitrile-methanol (73:19:8, v/v/v) and 20 mM dibasic ammonium phosphate
      buffer (pH 7.9)-acetonitrile-methanol (2:1:2, v/v/v). The limits of detection
      were 1-5 pmol, and calibration curves were linear for concentrations between 10
      and 4000 pmol. This rapid and reliable method is effective for measuring bile
      acid levels in the bile and serum not only of rats but also of patients with
      hepatobiliary and other diseases.

PMID- 8294534
TI  - Reversed-phase high-performance liquid chromatographic analysis of hydroxyproline
      and proline from collagen by derivatization with dabsyl chloride.
AB  - A high-performance liquid chromatographic method for the analysis of
      hydroxyproline and proline has been developed. The method is based on the
      derivatization of the secondary amino group with dabsyl-chloride after blocking
      of the primary amino group with o-phthalaldehyde. Dabsyl-hydroxyproline and
      dabsyl-proline were separated from other amino acids by high-performance liquid
      chromatography in the gradient elution mode, and eluted at 10.27 and 16.02 min,
      respectively. The correlations between the peak areas of dabsyl-hydroxyproline
      and dabsyl-proline were linear in the range from 20-200 pmol, with equations y =
      1.10x - 0.80 (r = 0.999) and y = 1.12x - 0.52 (r = 0.999), respectively. The
      method was applied to the analysis of rat tail collagen, and the contents of
      hydroxyproline and proline were 1.55 +/- 0.04 and 2.03 +/- 0.04 nmol/micrograms,
      respectively.

PMID- 8294535
TI  - Characterization of recombinant human extracellular superoxide dismutase.
AB  - Recombinant human extracellular superoxide dismutase produced in chinese hamster
      ovary cells has been characterized using several chromatographic methods. Peptide
      mapping confirmed the expected primary structure. The 15 amino acids at the N
      terminal end were sequenced and were in accordance with expectations in all
      positions. The C-terminal amino acids have been confirmed both by amino acid
      composition studies of a peptide of 42 amino acids and by specific sequential
      cleavage of the last three C-terminal amino acids with carboxypeptidase A. Both
      methods demonstrated a full length C-terminus. At physiological ionic strength,
      the dismutase exists for ca. 25% as octamers or larger polymers, and the amount
      of polymers increases at lower ionic strength.

PMID- 8294536
TI  - Detection of point mutations in DNA using capillary electrophoresis in a polymer
      network.
AB  - The use of capillary electrophoresis (CE) in a polymer network for single-strand
      conformation polymorphism (SSCP) is investigated. SSCP is a method to detect DNA
      point mutations, essential in the diagnosis of several diseases. The PCR
      (polymerase chain reaction) amplified p53 gene, a tumour suppressor gene known to
      be frequently mutated in malignant cells, was subjected to CE analysis. Two
      single-strand DNA fragments of 372 bp in length differing in only one nucleotide
      could be separated. We conclude that SSCP using CE in a polymer network is a
      powerful method for the detection of point mutations in DNA sequences.

PMID- 8294537
TI  - High-performance liquid chromatographic determination of N-nitroso-N-alkylureas
      by pre-column fluorescence derivatization and application to blood analysis.
AB  - A method for the derivatization and separation of N-nitroso-N-alkylureas [alkyl =
      methyl (NMU), ethyl (NEU), and n-butyl (NBU)] has been developed. Fluorescent
      derivatives were formed with sodium sulphide, taurine and o-phthalaldehyde and
      separated by reversed-phase high-performance liquid chromatography. The limits of
      detection of standard NMU, NEU and NBU were 0.25, 0.8 and 1.5 pmol/200
      microliters, respectively. The method was applied to the determination of NMU in
      blood after extraction with acetonitrile in the presence of calcium chloride. NBU
      was used as the internal standard. The recovery of NMU from blood was ca. 95%,
      and the limit of detection was 10 pmol/400 microliters blood. NMU levels in
      rabbit blood following a single oral administration were also measured.

PMID- 8294538
TI  - Ion-pair extraction and liquid chromatographic analysis of morphine in rat brain
      and plasma.
AB  - A highly efficient and reproducible two-step liquid-liquid ion-pair extraction
      technique for the isolation of morphine from biological samples is described. A
      rapid normal phase high-performance liquid chromatographic procedure coupled with
      amperometric electrochemical detection has also been developed for subsequent
      quantification of morphine. Extraction involves the disruption of brain tissue or
      plasma in methanol, centrifugation, evaporation and reconstitution in ethyl
      acetate containing 10 mM di-(2-ethylhexyl) phosphoric acid, a liquid cation
      exchanger, and back-extraction into 170 mM orthophosphoric acid. An acidic eluent
      consisting of acetonitrile-76 mM orthophosphoric acid-ammonia buffer (pH 3.0)
      (15:85, v/v) in combination with a strong cation-exchange column allows complete
      separation of morphine and the internal standard, nalbuphine. The limit of
      detection for morphine is 1.3 ng on-column.

PMID- 8294539
TI  - Determination of pilocarpine in aqueous humour by liquid chromatography
      atmospheric pressure chemical ionization mass spectrometry.
AB  - A new method has been developed for rapid analysis and determination of
      pilocarpine in aqueous humour using liquid chromatography-atmospheric pressure
      chemical ionization mass spectrometry. The chromatography was carried out on a
      reversed-phase phenyl column with 0.1% acetic acid-acetonitrile (95:5, v/v).
      Pilocarpine and its analogues, isopilocarpine, pilocarpic acid and isopilocarpic
      acid, were separated. An aqueous humour sample was deproteinized with methanol.
      After evaporation, the residue was dissolved in the mobile phase. The method was
      applied to the analysis of the metabolite in aqueous humour after the topical
      application of 2% pilocarpine (w/v) eye-drops. The main metabolite, pilocarpic
      acid, was easily identified. The protonated molecular ion of pilocarpine was used
      for the determination. The calibration curve had a good linearity within the
      concentration range investigated (2 ng to 10 micrograms/ml). The limit of
      determination was estimated to be an aqueous humour concentration of ca. 2 ng/ml.
      The method was applied to the determination of unchanged pilocarpine after the
      topical application of 2% pilocarpine (w/v) eye-drops.

PMID- 8294540
TI  - Determination of a cysteine protease inhibitor and its ethyl ester in mouse serum
      and muscle by liquid chromatography-mass spectrometry.
AB  - A liquid chromatographic-mass spectrometric method is described for the
      determination of a cysteine protease inhibitor (E64C) and its ethyl ester in
      mouse serum and muscle samples. The compounds in the sample, after
      deproteinization and solid-phase extraction, were separated by isocratic reversed
      phase high-performance liquid chromatography and detected by on-line mass
      spectrometry. The use of an aqueous mobile phase containing methanol and 30 mM
      ammonium trichloroacetate provided abundant protonated molecular ions of the
      compounds in the atmospheric pressure chemical ionization interface of the
      detection system. The method permitted the quantitative determination of the
      inhibitors without internal standards in the biological matrices. The detection
      limits for the compounds, in the selected-ion monitoring mode, were 10-15 pmol on
      column, at a signal-to-noise ratio of 5.

PMID- 8294541
TI  - Automated determination of free phenytoin in human plasma with on-line
      equilibrium dialysis and column-switching high-performance liquid chromatography.
AB  - Free phenytoin in human plasma was automatically determined by on-line
      equilibrium dialysis using the automated sequential trace enrichment of dialysate
      (ASTED) sample preparation system and HPLC. The dialysis cell was a modification
      of the cell supplied with the ASTED. Total phenytoin was analysed with the same
      analytical set-up and plasma protein binding was determined. Free phenytoin was
      determined in plasma from epileptic patients and the results were compared to
      those obtained by ultrafiltration. Automated determination of free and total
      phenytoin in plasma by the ASTED-HPLC combination was shown to be an accurate and
      reproducible method and the results in free phenytoin analyses were in agreement
      with those found with ultrafiltration. The sample throughput with the automated
      on-line combination of dialysis and column-switching HPLC was 75 samples in 24 h
      when the sample was dialysed at 37 degrees C.

PMID- 8294542
TI  - Evaluation of the stereoselective metabolism of the chiral analgesic drug
      etodolac by high-performance liquid chromatography.
AB  - The enantiomers of the racemic analgesic drug etodolac have been resolved by
      fractional crystallization of the diastereomeric salts with optically active 1
      phenylethylamine. A high-performance liquid chromatographic method to determine
      racemic etodolac (assay I) and its major metabolites (assay II) in urine using a
      conventional reverse-phase column is described. The determination of the
      enantiomeric ratios of etodolac and the two metabolites 7-hydroxyetodolac and 8
      (1'-hydroxyethyl)etodolac was achieved using different protein-bonded chiral
      stationary phases. The urinary data for five volunteers are presented and show a
      marked stereoselectivity of the metabolism of etodolac in humans.

PMID- 8294543
TI  - Dual ultraviolet wavelength high-performance liquid chromatographic method for
      the forensic or clinical analysis of seventeen antidepressants and some selected
      metabolites.
AB  - A sensitive method suitable for the determination of tricyclic and other
      antidepressants in postmortem and clinical specimens is presented. The procedure,
      which utilizes reversed-phase HPLC combined with dual ultraviolet wavelength
      detection, enables the separation of 17 commonly prescribed antidepressants and
      some selected metabolites in a single extraction. Peak purity was confirmed using
      absorbance ratios at 220 nm and 254 nm wavelengths and revealed little
      interference from other eluting analytes. The blood detection limit for most
      antidepressants was 50 ng/ml. The most commonly observed antidepressants in 281
      forensic cases analysed over a two-year period with the described method were
      dothiepin, amitriptyline, nortriptyline and doxepin.

PMID- 8294544
TI  - Chiral high-performance liquid chromatographic determination of oxprenolol in
      plasma.
AB  - A sensitive, stereospecific high-performance liquid chromatographic assay for
      oxprenolol enantiomers in rat plasma was developed, using a chiral derivatization
      agent. Racemic oxprenolol and the internal standard (racemic propranolol) are
      extracted with dichloromethane after alkalinization of the plasma. Quantitation
      of R(+)- and S(-)-oxprenolol is based on derivatization with the chiral agent S(
      )-1-(1-naphthyl)-ethyl isocyanate, followed by chromatographic separation on a
      C18 reversed-phase column, with fluorometric detection (excitation at 226 nm,
      emission at 333 nm). The assay is reproducible as judged by a coefficient of
      variation of less than 17.5% for both enantiomers at all concentrations used.
      Preliminary experiments in the rat demonstrate that the method is sufficiently
      sensitive for pharmacokinetic studies in that species.

PMID- 8294545
TI  - Investigation of the metabolic fate of the neuroleptic drug haloperidol by
      capillary electrophoresis-electrospray ionization mass spectrometry.
AB  - Combined capillary electrophoresis-mass spectrometry (CE-MS) is a powerful
      analytical tool for the characterization of components of complex mixtures.
      Furthermore, when interfaced with an electrospray ionization (ESI) source,
      skimmer induced fragmentation can yield structural information that aids compound
      identification. We show that these techniques can be used to probe the metabolic
      fate of drugs by investigation of the phase I metabolism of the widely used
      neuroleptic drug haloperidol. In addition, we demonstrate differences of in vitro
      metabolism of haloperidol by mouse and guinea pig hepatic microsomes.

PMID- 8294546
TI  - Simultaneous determination of nitrazepam and its metabolites in urine by micellar
      electrokinetic capillary chromatography.
AB  - We applied micellar electrokinetic capillary chromatography to simultaneous
      separation and determination of nitrazepam and its major metabolites, 7
      aminonitrazepam and 7-acetamidonitrazepam, in spiked urine. Prior to
      electrophoresis, the three compounds were successfully extracted from the spiked
      urine with commercial disposable solid-phase cartridges. The optimum running
      buffer for the separation was prepared by combining 85 parts of 60 mM sodium
      dodecyl sulphate-6 mM phosphate-borate, adjusted to pH 8.5, with 15 parts of
      methanol. The separation order, completed within 25 min, was 7-aminonitrazepam >
      7-acetamidonitrazepam > nitrazepam, at an applied potential of 20 kV. We obtained
      reproducible electropherograms in successive repetitions, and few other peaks or
      interferences appeared in the electropherogram. The detection limits of the three
      compounds were 50-100 pg (0.1-0.2 microgram/ml of analyte in spiked urine), and
      the recoveries were 78.9-100.8% for 1 microgram/ml and 84.1-100.3% for 5
      micrograms/ml. The application of this method to forensic or clinical samples is
      demonstrated.

PMID- 8294547
TI  - Determination of nicotine and four metabolites in the serum of smokers by high
      performance liquid chromatography with ultraviolet detection.
AB  - A simple and reliable reversed-phase high-performance liquid chromatographic
      method with ultraviolet detection is described for the quantitation of nicotine
      and its metabolites cotinine, trans-3'-hydroxycotinine, norcotinine and cotinine
      N-oxide in human serum. The analytes and the internal standard, N
      ethylnorcotinine, were extracted by solid-phase extraction before chromatography.
      Two different columns and mobile phases with gradient systems were used. The
      detection limit of the assay was 10 ng/ml for nicotine, 3 ng/ml for cotinine N
      oxide and 5 ng/ml for cotinine, trans-3'-hydroxycotinine and norcotinine. The
      concentrations of nicotine and its metabolites in the serum of 12 cigarette
      smokers are reported.

PMID- 8294548
TI  - Cytokine production by cells in cerebrospinal fluid during experimental allergic
      encephalomyelitis in SJL/J mice.
AB  - Cytokine production by T cells in the cerebrospinal fluid (CSF) and central
      nervous system (CNS) of SJL/J mice during myelin basic protein (MBP)-induced
      experimental allergic encephalomyelitis (EAE) was examined. Reverse
      transcriptase/polymerase chain reaction (RT/PCR) was used to measure interleukin
      2 (IL-2) and interferon-gamma (IFN-gamma) mRNA levels from perfused CNS tissue
      (brain and spinal cord) and from cells isolated from CSF. Animals were grouped
      according to EAE severity, ranging from asymptomatic (adjuvant only) to severe
      disease (paralysis or severe paresis). Cytokine signals, normalized to actin,
      were almost undetectable in control tissues, and only slightly elevated in whole
      CNS tissue from animals with mild EAE. Both cytokine messages were strongly
      upregulated in CNS tissues derived from severely affected animals, consistent
      with previous observations correlating disease progression with infiltration by
      memory/effector CD4+ T cells, the major source of these cytokines. This cytokine
      upregulation was specific to the CNS, since other organs from the same animals
      did not express significant levels of IL-2 and IFN-gamma. CSF was obtained from
      the cisterna magna of unperfused mice and verified as such by absence of red
      blood cells (RBCs) and by immunoglobulin concentration orders of magnitude lower
      than in serum. Cytokine message was measured in RNA isolated from cells in CSF.
      Levels of IL-2 and IFN-gamma mRNA in CSF cells were significantly elevated in
      mild EAE and strongly upregulated in severe disease, correlating with those in
      total CNS tissue. These results confirm the CSF as representative of the immune
      status of the CNS and indicate a role for IL-2 and IFN-gamma in inflammatory CNS
      disease.

PMID- 8294549
TI  - Polyclonal and oligoclonal IgA synthesis in the cerebrospinal fluid of
      neurological patients: an immunoaffinity-mediated capillary blot study.
AB  - An intrathecal synthesis of IgA has been reported in various neurological
      disorders. However, the frequency of its occurrence and the electrophoretic
      characteristics of the locally produced IgA remained a matter of controversy. We
      developed a sensitive immunoaffinity-mediated capillary blot technique for the
      detection of polyclonal and oligoclonal IgA in the CSF of 115 patients with
      various neurological disorders. Paired CSF and serum samples containing 50 ng IgA
      after appropriate dilutions were submitted to isoelectric focusing in agarose
      gels; IgA was then blotted onto a polyvinylidene difluoride sheet coated by an
      anti-IgA antiserum or by infectious antigens. The immunoblots were revealed by an
      alkaline phosphatase-conjugated anti-IgA antiserum. Only five samples displayed
      CSF-restricted oligoclonal IgA bands, including two out of 33 from MS patients.
      In herpetic encephalitis (n = 5) and varicella-zoster meningitis (n = 2), a
      strong intrathecal production of virus-specific IgA antibodies was detectable. In
      such cases, faint oligoclonal IgA antibodies were superimposed on a polyclonal
      background. A weak local production of anti-Borrelia burgdorferi IgA antibodies
      was present in two out of four cases of neuroborreliosis.

PMID- 8294550
TI  - Lack of m2 muscarinic acetylcholine receptor mRNA in rat lymphocytes.
AB  - The presence of muscarinic acetylcholine receptors on lymphocytes has been
      demonstrated by radioligand binding experiments. Although the specific subtype(s)
      of muscarinic acetylcholine receptors expressed in lymphocytes is still unknown,
      some reports suggest the presence of the m2 subtype. In this study we analyzed
      the expression of m2 subtype mRNA in rat mononuclear cells, B lymphocytes and T
      lymphocytes by Northern blot hybridization and reverse transcription-polymerase
      chain reaction. Positive signals for the presence of m2 mRNA were found in rat
      heart, brainstem, cerebral cortex, corpus striatum and hippocampus, which were
      used as positive controls. On the other hand, no expression of m2 was detected in
      lymphocytes. These results indicate that mRNA for the m2 subtype is absent in rat
      lymphocytes and that one or more other subtypes may be responsible for the
      reported results in binding experiments.

PMID- 8294551
TI  - Induction of interleukin-1 in various brain regions after peripheral and central
      injections of lipopolysaccharide.
AB  - The presence of bioactive interleukin-1 (IL-1) in various brain regions
      (cerebellum, cortex, brainstem, diencephalon or hippocampus) after either
      intraperitoneal (i.p.) or intraventricular (i.c.v.) injection of
      lipopolysaccharide (LPS) was studied in the rat. To detect IL-1, extracellular
      fluid and cell lysate were fractionated by gel exclusion chromatography and
      fractions tested for thymocyte stimulation; presence of IL-1 was confirmed by
      blockade of stimulation by addition to the assay of a monoclonal antibody (mAb)
      to IL-1 receptor. When LPS was infused i.c.v., IL-1 was detected in the brainstem
      and diencephalon 2 h after injection, and in all the brain regions except
      cerebellum 6 h after injection; IL-1 was not detected in the plasma of these
      animals. When LPS was injected i.p., IL-1 was detected in the plasma but not in
      the brain 2 h after the injection, and in all brain regions but not in the plasma
      6 h after the injection. In all of these cases, IL-1 was found in extracellular
      fluid; in some cases (cortex, cerebellum) cell lysate of the region did not
      produce detectable bioactivity, thereby indicating that IL-1 in these brain
      regions is processed to active peptide during release, as has been reported in
      the periphery. In those cases where bioactivity was detected in cell lysate
      (brainstem, diencephalon), bioactivity was not blocked by IL-1 receptor mAb,
      indicating presence of a non-IL-1 stimulating factor. These results further
      support the idea that IL-1 is secreted by cells in the brain, and indicate that
      it is found in the extracellular fluid of many brain regions following an
      appropriate stimulus in the periphery as well as in the brain.

PMID- 8294552
TI  - Antibody of patients with Guillain-Barre syndrome mediates complement-dependent
      cytolysis of rat Schwann cells: susceptibility to cytolysis reflects Schwann cell
      phenotype.
AB  - We previously observed that demyelination of dissociated dorsal root ganglion
      cultures by acute phase serum of some Guillain Barre syndrome (GBS) patients was
      associated with cytolysis of rat Schwann cells (SC) not committed to myelination.
      In this study, to determine if SC cytolysis was antibody (Ab) and complement
      dependent and if SC at various stages of differentiation were uniformly
      susceptible, sciatic nerve SC from 1-2-day-old (SC/2d) or 6-day-old (SC/6d)
      Sprague Dawley rats were sensitized with IgM from GBS patients or normal controls
      and incubated at 37 degrees C for 60 min with 25% guinea pig serum complement.
      Cytolysis was detected by vital dye exclusion. IgM Ab of 11 GBS patients induced
      complement-mediated cytolysis of 10.7-64.1% SC/2d (38.3 +/- 18.8; mean +/- SD)
      which was significantly higher than cytolysis of SC/6d (8.5-32%) or that by
      normal controls (15.0 +/- 15.2 SC/2d; 8.3 +/- 3.3 SC/6d mean +/- SD, n = 11).
      Culture of SC/6d increased their cytolysis by IgM plus complement to the levels
      similar to that of SC/2d. FACS analysis suggested that the greater sensitivity of
      SC/2d to cytolysis did not reflect greater antibody binding since 2.6-fold less
      GBS IgM was required to initiate SC/2d lysis compared to SC/6d. This suggested
      that the less differentiated SC were more susceptible to complement-mediated
      cytolysis.

PMID- 8294553
TI  - The effect of TCR V beta 8 peptide protection and therapy on T cell populations
      isolated from the spinal cords of Lewis rats with experimental autoimmune
      encephalomyelitis.
AB  - Vaccination or treatment of Lewis rats with TCR V beta 8 peptides can prevent or
      reverse the clinical signs of experimental autoimmune encephalomyelitis (EAE)
      which is mediated predominantly by V beta 8.2+ CD4+/CD45R lo T cells. However,
      rats protected or treated with V beta 8 peptides still developed histological
      lesions in the spinal cord (SC), even though they remained clinically well. We
      sought to discern phenotypic changes characteristic of these SC infiltrating
      lymphocytes. In particular, we focused on whether the immunoregulatory mechanism
      induced by TCR peptides caused a reduction of V beta 8.2+ T cells, or induced
      changes in CD45R lo or hi/CD4+ subpopulations that have been associated
      respectively with EAE induction or recovery. In the V beta 8 peptide vaccinated
      rats there was a dramatic decrease in the number of V beta 8.2+ T cells isolated
      from the SC early in disease. During the recovery phase, however, the number of V
      beta 8.2+ SC T cells was similar in protected and control groups; in contrast,
      there was striking reduction in the number and size of CD45R hi/CD4+ T cells in
      the protected animals. In rats treated with V beta 8.2 peptide, no changes were
      observed in the number of SC V beta 8.2+ T cells or expression of V beta 8.2
      message, but similar to vaccinated rats, there was a marked decrease in the
      number of CD45R hi/CD4+ T cells. These data suggest that vaccination with TCR
      peptides prevented the initial influx of encephalitogenic V beta 8.2+ T cells
      into the central nervous system (CNS), whereas treatment appeared to inactivate V
      beta 8.2+ T cells already present in the CNS. In both cases, TCR peptide-induced
      inhibition of the encephalitogenic T cells apparently preempted the need for
      CD45R hi/CD4+ T cells that may normally be necessary to resolve the disease.

PMID- 8294555
TI  - Effect of pure bovine brain-derived gangliosides on normal human B cell
      proliferation in vitro.
AB  - Pure gangliosides obtained from bovine brain including GM1, GD1b, GT1b and asialo
      GM1 (GA1) did not induce normal human B cell proliferation in vitro. No B cell
      proliferation was observed either when GM1 was tested in the presence of
      interleukin-2 (IL-2), IL-4 or IL-6. Furthermore, the proliferative responses of
      human B cells induced by Staphylococcus aureus Cowan I (SAC), a T cell
      independent B cell mitogen, were inhibited by these gangliosides. The degree of
      inhibition was influenced by ganglioside-bound sialic acid, although sialic acid
      per se was not inhibitory. Strongest inhibition was observed in the presence of
      GT1b (EC50 8.8 microM/10(5) B cells) and lowest in the presence of GA1 (EC50
      129.5 microM/10(5) B cells) with intermediate values for GM1 and GD1b. GM1
      inhibition of SAC-induced B cell proliferation did not represent cytotoxic
      effects and was still evident when GM1 was added 24-48 h after the beginning of
      the cultures. GM1 inhibition of SAC-induced proliferation was not reversed by the
      addition of IL-2, IL-4, IL-6 or their combination. In addition, GM1 inhibited the
      ILs-driven proliferative responses of SAC-induced B cell blasts. However, no
      inhibition of Epstein-Barr virus-induced B cell proliferative responses was
      observed. In conclusion, these results show that bovine brain-derived
      gangliosides do not induce proliferative responses of normal human B cells but,
      on the contrary, inhibit B cell responses induced by SAC.

PMID- 8294554
TI  - Cytokine-gene expression in measles-infected adult human glial cells.
AB  - The expression of interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)
      alpha transcripts in cultured human glial cells was examined using reverse
      transcription followed by polymerase chain reaction (PCR) amplification and
      Southern blot quantitation. Microglial cultures derived from brain biopsy
      specimens from three different individuals expressed transcripts for the three
      cytokines under basal culture conditions. This expression was enhanced in
      response to measles virus (MV) infection (IL-1 beta, 2.2-8.8-fold; IL-6, 2.5-8.4
      fold; TNF alpha, 2.2-3.2-fold). Neither IL-1 beta nor TNF alpha transcripts were
      detectable in undissociated brain tissue from two individuals, suggesting that
      the basal expression of these cytokines in culture may have been induced by
      tissue dissociation or by the culture conditions. Oligodendrocytes did not
      express cytokine transcripts under basal culture conditions, and IL-1 beta and IL
      6 but not TNF alpha transcripts could be induced by MV. Similarly, meningeal
      fibroblasts expressed IL-1 beta and IL-6 but not TNF alpha in response to MV
      infection, suggesting that the production of TNF alpha is more cell type
      restricted than either IL-1 beta or IL-6. The results indicate that adult human
      microglia can participate in the inflammatory response to MV infection in the CNS
      by producing cytokines that contribute to inflammation and demyelination. In
      addition, besides their role in myelination, oligodendrocytes can potentially
      influence immunoreactivity in the CNS by producing IL-1 beta and IL-6.

PMID- 8294556
TI  - Fc receptor for IgG (FcR) on rat microglia.
AB  - Receptor for IgG (FcR) was demonstrated on rat microglia in vivo and in vitro by
      immunohistochemical staining with immune complexes of horseradish peroxidase
      (HRP) and rabbit IgG anti-HRP. Astrocytes, oligodendrocytes and neurons did not
      express FcR. Microglia in culture also showed FcR-mediated agglutination and
      phagocytosis of IgG-sensitized erythrocytes. A radiolabelled cDNA probe for rat
      FcRIII hybridized with a 1.4-kb RNA band in Northern blots prepared from total
      RNA from rat brain. FcRIII mRNA-positive cells in rat brain, presumably
      microglia, were demonstrated by in situ hybridization. FcR participates in the
      initiation of cytotoxic responses and of phagocytosis by microglia and is
      therefore likely to be important in mediating immune reactions in the brain.

PMID- 8294557
TI  - Effects of a chronic inflammatory stress on levels of pro-opiomelanocortin
      derived peptides in the rat spleen and thymus.
AB  - Adjuvant-induced arthritis (AA) in specific strains of rats is an immunologically
      mediated inflammatory disease which is also characterised by activation of the
      endocrine system. To further investigate the effects of AA on processing of the
      pro-opiomelanocortin (POMC) precursor in rat immune tissues, we utilised
      radioimmunoassays for adrenocorticotrophin (ACTH), beta-endorphin and alpha
      melanocyte-stimulating hormone (alpha-MSH) to measure these peptides in the
      spleen and thymus. 14 days following adjuvant injection, spleen levels of ACTH
      were elevated in the AA group (4.47 +/- 1.04 ng/g tissue, n = 9) compared to
      controls (2.42 +/- 0.4 ng/g) and exacerbation of the disease by removal of
      circulating glucocorticoids through bilateral adrenalectomy (ADX) resulted in
      further elevation of spleen ACTH (5.11 +/- 1.22 ng/g). beta-Endorphin levels in
      both the AA (10.60 +/- 1.61 ng/g) and AA/ADX (13.37 +/- 2.36 ng/g) groups were
      higher than controls (5.57 +/- 0.65 ng/g). Conversely, alpha-MSH spleen levels
      were decreased in the AA (2.89 +/- 0.22 ng/g) and AA/ADX (2.22 +/- 0.33 ng/g)
      groups compared to controls (4.62 +/- 0.45 ng/g) and were also decreased
      following adrenalectomy. In the thymus, ACTH levels were elevated in the AA group
      (8.95 +/- 1.41 ng/g) compared to controls (5.79 +/- 0.63 ng/g), and the same
      pattern was evident for thymic alpha-MSH (0.64 +/- 0.08 ng/g in AA animals
      compared to control levels of 0.35 +/- 0.03 ng/g). Following G50 gel filtration,
      ACTH and beta-endorphin immunoreactivities (ir) were present in both spleen and
      thymus as two peaks, one which eluted near the void volume and one which eluted
      in a lower molecular mass position than the standards.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8294558
TI  - Relationships between monoaminergic and cholinergic innervation of the rat thymus
      during aging.
AB  - The present study has been undertaken in order to investigate whether aging is
      accompanied by alterations in the thymic autonomic innervation. The results
      showed that in aged rats compared to young adult rats the density of
      monoaminergic histofluorescent nerve profiles decreased remarkably, while their
      pattern of intrathymic distribution remained unchanged. The thymic concentrations
      of noradrenaline (NA) and dopamine (DA) also significantly decreased between the
      age of 12 and 18 months. However, the density of thymic autofluorescent cells
      (afc) markedly increased over the same period, as well as the concentration of 5
      hydroxytryptamine (5-HT). The aged rat thymus seemed to be able to maintain its
      cholinergic innervation in terms of density and pattern of distribution, while
      the density of cells with intracytoplasmic acetylcholinesterase (AChE) staining
      even increased. The neurochemical measurement showed an increase in the activity
      of AChE between the age of 9 to 18 months. The results indicate an altered
      relation between the components of thymic autonomic innervation of aged rats that
      might be related to the reduced immunocompetence of their T cells.

PMID- 8294559
TI  - A potential role for human herpesvirus type 6 in nervous system disease.
AB  - Human herpesvirus type 6 (HHV-6) is a new representative of the herpesvirus
      family which was associated with a spectrum of diseases, including myalgic
      encephalitis, meningitis and the chronic fatigue syndrome. We set out to study
      the potential role of HHV-6 in multiple sclerosis (MS) (n = 21), facial palsy
      (FP) (n = 19) and Guillain-Barre-syndrome (GBS) (n = 7). Results were compared
      with a control group (CG) (n = 16). We analyzed paired samples of serum and
      cerebrospinal fluid (CSF) with the polymerase chain reaction (PCR) for the
      presence of HHV-6 DNA. The studies were complemented by ELISA determination of
      serum antibodies against HHV-6. In the MS group we detected HHV-6 DNA in the CSF
      from three of 21 (14.3%) patients but not in the corresponding serum samples. In
      FP, GBS and controls CSF and serum PCRs were negative in all cases. HHV-6 serum
      antibody titers were significantly higher in MS compared with FP, GBS and
      controls. These findings suggest that HHV-6 may play a role in MS.

PMID- 8294560
TI  - A chemiluminescence assay to detect antibodies to brain surface antigens in human
      sera.
AB  - A chemiluminescence assay was developed based on the interaction between
      antibodies binding to the surface of living brain cells in culture and
      macrophages. Such interaction leads to production of reactive oxygen radicals
      which can be measured by a chemiluminescence assay. This assay was used to detect
      anti brain antibodies in serum samples from humans with various neurological
      diseases. Such antibody activity was found in a high proportion of these
      patients. Subsequent experiments with purified IgG fractions and corresponding
      F(ab')2 fragments showed that the observed reactions were highly specific. It was
      concluded that the chemiluminescence assay is a sensitive and useful technique to
      detect autoantibodies in neurological diseases.

PMID- 8294561
TI  - Kinetics of glucocorticoid response to restraint stress and/or experimental
      influenza viral infection in two inbred strains of mice.
AB  - The murine model of influenza viral infection was used to evaluate the effects of
      restraint stress on pathogenesis and survival in inbred strains of mice. We
      recently reported that restraint stress was associated with an enhanced
      probability of survival in one strain of inbred mouse, DBA/2, and not in another,
      C57BL/6. Those studies suggested that the protective mechanism(s) of stress on
      mortality in the DBA/2 mice might be attributable to elevated levels of
      circulating glucocorticoids. Therefore, daily levels of plasma glucocorticoids
      were measured during influenza viral infection in both these strains. The present
      studies demonstrated that influenza infection itself is perceived as a stressor
      in both C57BL/6 and DBA/2 mice as evidenced by elevated plasma glucocorticoid
      levels within 48 h of infection. However, augmentation of glucocorticoid levels
      was not seen in the DBA/2 mice that were also subjected to restraint stress
      during the course of infection. Thus, corticosterone levels alone did not account
      for the enhanced survival seen in this group of animals.

PMID- 8294562
TI  - Effects of streptozotocin-induced diabetes on lymphocyte POMC and growth hormone
      gene expression in the rat.
AB  - Diabetes in the rat is associated with a change in the profiles of several
      neuroendocrine hormones resulting in poor growth and decreased immune function.
      Since lymphocytes can also serve as a source of neuroendocrine hormones, we have
      examined whether the change in hormone profiles are accompanied by an impairment
      of lymphocyte GH and POMC gene expression in the immune system. Diabetes was
      induced by the administration of streptozotocin (STZ; 10 mg/100 g body weight)
      and 3 days later GH and ACTH protein and mRNA were determined. The results show a
      modest diminution of GH RNA in the spleen of diabetic animals whereas the
      expression of POMC mRNA and ACTH by the thymus was enhanced. The expression of
      POMC in the spleen appeared unaltered while the increase of POMC RNA in the
      thymus was evident after the first day of STZ treatment. STZ had no direct effect
      on GH or POMC expression in the spleen or thymus cells in vitro. Insulin does not
      appear to be involved in the expression of lymphocyte GH or POMC. The
      administration of insulin to the diabetic animals had no significant effect on
      the expression of GH or POMC by the immune cells. In addition, lymphocytes do not
      appear to serve as a source of insulin or are the expression of genes for
      lymphocyte GH or ACTH altered by insulin in vitro. Taken together, the findings
      are the first to report on the expression of neuroendocrine genes in lymphocytes
      during diabetes. The mechanism for the inhibition of GH and stimulation of POMC
      expression by lymphocytes in diabetic animals is unknown, but it is tempting to
      speculate an important role in the development of the autoimmunity that
      characterizes this complex disease.

PMID- 8294563
TI  - Sympathetic nervous system modulation of the immune system. II. Induction of
      lymphocyte proliferation and migration in vivo by chemical sympathectomy.
AB  - We have used chemical sympathectomy with 6-hydroxydopamine (6-OHDA) in adult mice
      to study the role of the sympathetic nervous system (SNS) in regulating cellular
      proliferation and migration in lymphoid organs. Following sympathectomy, an
      increase in inguinal and axillary lymph node (LN) weight and cellularity was
      observed. This increase paralleled increased cellular proliferation in vivo, as
      measured by uptake of [125I]deoxyuridine (125IUdR). Transient increases in
      cellular proliferation also were observed in spleen and bone marrow following
      sympathectomy. Administration of desipramine prior to 6-OHDA to prevent
      sympathectomy resulted in control levels of proliferation. beta-Adrenoceptor
      blockade just prior to or following 6-OHDA treatment did not alter the enhanced
      proliferation. Migration of normal 51Cr-labelled lymphocytes into inguinal and
      axillary LN was enhanced in sympathectomized recipients. Conversely, cells from
      sympathectomized animals showed diminished migration to these LN upon transfer
      into intact recipients. These results demonstrate that depletion of NA
      innervation alters cellular proliferation and lymphocyte migration in primary and
      secondary lymphoid organs.

PMID- 8294564
TI  - Sympathetic nervous system modulation of the immune system. III. Alterations in T
      and B cell proliferation and differentiation in vitro following chemical
      sympathectomy.
AB  - Functional changes in lymph node (LN) and spleen lymphocytes were examined
      following sympathetic denervation of adult mice with 6-hydroxydopamine (6-OHDA).
      Sympathectomy reduced in vitro proliferation to concanavalin A (ConA) by LN cells
      and decreased LN Thy-1+ and CD4+ T cells. At the same time, ConA-induced
      interferon-gamma (IFN-gamma) production was increased, but interleukin-2 (IL-2)
      production was not altered. After sympathectomy, lipopolysaccharide (LPS)
      stimulated proliferation of LN B cells was enhanced, in parallel with an increase
      in the proportion of sIgM+ cells. LPS-induced polyclonal IgM secretion was
      decreased, whereas polyclonal IgG secretion was dramatically enhanced. In the
      spleen, ConA and LPS responsiveness was reduced after sympathectomy, as was IL-2
      and IFN-gamma production. The decreased proliferation was not associated with
      changes in splenic T and B cell populations. The uptake blocker desipramine
      prevented the 6-OHDA-induced changes in spleen and LN, indicating that these
      alterations were dependent upon neuronal destruction. These results provide
      evidence for heterogeneity of sympathetic nervous system regulation of T and B
      lymphocyte function and for organ-specific influences on immune function.

PMID- 8294565
TI  - T cell-dependent activity of ganglioside GM1-specific B cells in Guillain-Barre
      syndrome and multifocal motor neuropathy in vitro.
AB  - Synthesis of anti-ganglioside GM1 antibodies of the IgM class by peripheral blood
      mononuclear cells (PBMNC) from patients with immune-mediated neuropathies and
      motor neuron diseases and from normal controls was stimulated by Pokeweed mitogen
      (PWM) in vitro. In patients with acute Guillain-Barre syndrome or multifocal
      motor neuropathy and high serum titers of IgM anti-ganglioside GM1 antibodies
      this culture response was greatly enhanced as compared to controls and already
      detectable in unstimulated cultures. Limiting dilution analysis demonstrated high
      frequencies of GM1-specific B cells in these patients. Anti-ganglioside GM1
      antibodies of the IgG and IgA class were only produced by PBMNC from patients
      with Guillain-Barre syndrome corresponding to serum titers. In cultures taken at
      intervals over 6 months in vitro B cell activity for IgM, IgG and IgA anti
      ganglioside GM1 antibodies in two Guillain-Barre syndrome patients declined
      accompanied by clinical improvement and falling serum titers. We conclude that
      GM1-specific PWM-responsive B cells pre-exist in peripheral blood and respond to
      T cell-dependent stimulation in Guillain-Barre syndrome and multifocal motor
      neuropathy.

PMID- 8294566
TI  - Development of a competitive double antibody radioimmunoassay for rat
      metallothionein.
AB  - A competitive double antibody radioimmunoassay (RIA) for rat metallothionein (MT)
      has been developed that has a detection limit of 100 pg and a range of 100 to
      100000 pg. The antibody was raised in rabbits against rat MT-2 but it crossreacts
      equally with MT-1 and MT-2. However, when the assay is done in the presence of 2
      mercaptoethanol the antibody is more specific for MT-2. Zn- and Cd- saturated MTs
      have similar responses in the assay. Addition of Cu(II) to Zn-MT (more than 6 mol
      Cu/mol MT) in non-reducing conditions modifies the response of the antibody,
      probably because of Cu(II) oxidation and later MT polymerization. Standard curves
      developed in the presence of cytosols from brain cortex, hypothalamus or liver
      did not differ from the standard curve, indicating the absence of interfering
      substances in the assay. Furthermore, serial dilutions of those cytosols
      paralleled the response of the standard curve, indicating that the response of
      the antibody was specific. For comparison, MT levels in some brain areas measured
      with the present RIA were compared with those measured with an established RIA.
      In addition, the expected effect of dexamethasone and stress on liver MT levels
      was clearly identified by this RIA. The results suggest that the present RIA can
      be used for quantitation of metallothionein.

PMID- 8294568
TI  - The effects of PEG on second antibody immunoprecipitation and its use in
      immunoassay.
AB  - The effects of PEG on the second antibody immunoprecipitation have been studied
      in several radioimmunological systems. The following parameters have been studied
      in the assays: the average molecular weight and concentration of PEG, the species
      of the animal producing the first and second antibody, the nature of the antigen,
      the concentration of carrier immunoglobulins, and the rate of the
      immunoprecipitation. Thus, optimal conditions for the use of PEG with a second
      antibody have been defined in order to be used in any liquid phase immunoassay.

PMID- 8294567
TI  - Immunoassays for des-Arg9-bradykinin.
AB  - Splenocytes from a female, BALB/c mouse immunized with bradykinin conjugated to
      ovalbumin with toluene diisocyanate were fused with mouse myeloma cells,
      X63/Ag8.653, using polyethylene glycol. Seventy-nine hybridomas were identified
      by ELISA to be making kinin reactive antibodies. In preliminary specificity
      studies it was determined that all of these hybridomas were producing antibodies
      more reactive with des-Arg9-bradykinin than with bradykinin. ELISAs were
      developed with the five clones that displayed the highest affinities for des-Arg9
      bradykinin. Radioimmunoassays were developed for 3 of these 5 clones as well as
      with 5 monoclonal antibodies previously described (Odya and Lee 1990). The most
      sensitive des-Arg9-bradykinin assay developed was a radioimmunoassay in which
      carboxypeptidase B-treated [Tyr5]-bradykinin was the labeled antigen, clone OLNBK
      5 was the antibody, and dextran-coated charcoal was used to separate bound from
      free radioactivity. The concentration of des-Arg9-bradykinin that inhibited 50%
      of the radioactive peptide binding was 0.08 +/- 0.03 nM. The relative specificity
      of this assay (des-Arg9-bradykinin = 100%) was: 29% bradykinin and about 1% with
      each of the following: lysyl-bradykinin, methionyl-lysyl-bradykinin, des-Arg1
      bradykinin and des-Phe8-Arg9-bradykinin.

PMID- 8294569
TI  - Enzyme-linked immunosorbent assay for the phytotoxin thevetin.
AB  - An enzyme-linked immunosorbent assay is reported for monitoring thevetin, an
      active constituent of the highly poisonous plant Thevetia nerifolia. A thevetin
      BSA conjugate was employed as the immunogen and the antibodies raised in rabbits
      were used for the development of an ELISA. Penicillinase served as the marker
      enzyme and its conjugation to thevetin by the periodate method is reported for
      the first time. The present ELISA method could detect 2 ng/ml of thevetin. Cross
      reactivity studies with structural analogues and other phytotoxins and drugs of
      common occurrence in clinical and forensic toxicology established the superiority
      of the ELISA over the existing analytical methods for determining thevetin in
      various biospecimens.

PMID- 8294570
TI  - Solid phase radioimmunoassay for the determination of aldosterone excretion.
AB  - A solid phase radioimmunoassay (SP-RIA) was developed for the determination of
      urinary conjugated aldosterone. Acid-hydrolyzed urine was extracted with
      dichloromethane and the extract was analyzed by SP-RIA. Microtiter plates were
      coated with two different anti-aldosterone antisera (S-3: against aldosterone-21
      hemisuccinate-BSA and 58: aldosterone-3-(O-carboxymethyl)-oxime-BSA separately
      and preincubated with 3H-aldosterone. Reference values were obtained using a
      liquid radioimmunoassay method including paper chromatography. Regression
      analysis revealed for S-3: Y = 0.8 X + 3.2, r = 0.84; p < 0.0001; n = 36 and for
      58: Y = 1.16 X + 1.2, r = 0.89; p < 0.0001; n = 36. The SP-RIA assay is useful
      for routine measurement of conjugated aldosterone excretion. The method is time
      saving and does not require paper chromatography, and is adequate for many
      clinical purposes.

PMID- 8294571
TI  - Compensatory renal growth in children and adults studied by Doppler sonography.
AB  - To identify modifications of kidney morphology and of the time-velocity spectral
      waveform associated with long-term compensatory hypertrophy, spectral Doppler
      sonography was performed in 30 children and adults with solitary kidneys 7 years
      to 28 years following nephrectomy. Doppler signals were obtained from three
      arterial sites in each kidney. The average renal volume was 207 mL and the mean
      hypertrophy of the kidneys was 186%. The mean value of pulsatility (PI) and
      Pourcelot (RI) indexes of solitary hypertrophied kidneys was significantly lower
      than that of normal paired kidneys or allografts with normal function described
      in the literature. The PI and RI were found to correlate inversely with the
      kidney volume and the body surface area (BSA). In spite of a long follow-up time,
      no patient suffered from renal failure. This study suggests that in the case of
      solitary kidney, specific ranges of PI and RI should be employed rather than
      those used with paired kidneys.

PMID- 8294572
TI  - Ultrasonographic evaluation of the biliary tree in patients with atypical chest
      pain.
AB  - We studied the use of gallbladder ultrasonography in the evaluation of atypical
      chest pain (ACP). During an 8-month period, 52 patients were referred for biliary
      ultrasonography with a chief complaint of chest pain. Twelve (32.1%) had
      cholelithiasis discovered by ultrasonography. Four of these 12 (33.3%) underwent
      subsequent cholecystectomy with complete relief of symptoms. None of the patients
      with normal ultrasonography for whom follow-up was available (32) underwent
      subsequent cholecystectomy. We found no statistical difference in the prevalence
      of cholelithiasis between the ACP group and 85 asymptomatic controls. Clinical
      evidence confirms the concept that ultrasonography may play an important role in
      the evaluation of ACP.

PMID- 8294573
TI  - Myocardial contrast echocardiography: enhancement of perfusion images by color
      coding.
AB  - To determine whether real-time color coding enhances the detection of myocardial
      perfusion through the use of echocardiographic contrast agents, we used a
      recently developed real-time color system during contrast injection in six open
      chest dogs. Small amounts of echocardiographic contrast were injected into the
      left atrium. Short-axis epicardial images were obtained with a 5-MHz transducer
      before and after left anterior descending artery ligation. Gray-scale and rainbow
      color map images were obtained for each contrast agent. The color map allowed
      detection of small increments in echo intensity that were not evident with
      routine gray-scale imaging. Thus, real-time color coding may improve the
      detection of myocardial perfusion with echocardiographic contrast agents.

PMID- 8294574
TI  - A comparison between preoperative magnetic resonance and intraoperative
      ultrasound tumor volumes and margins.
AB  - A major obstacle in surgical neuro-oncology is differentiating the interface
      between tumor and normal brain. Twenty-two brain tumors were evaluated
      preoperatively with magnetic resonance imaging. Intraoperative ultrasonography
      was used to guide surgical resection of these tumors, and results were compared
      with surgical and pathologic findings. Ultrasound tumor volume estimates were
      larger than T1 gadolinium-enhanced and T1 non-gadolinium-enhanced volumes, but
      these differences did not reach statistical significance. Similarly T2 volumes
      were larger than the corresponding sonographic volumes, except for the subset of
      low-grade gliomas, and in that instance the difference was small, but again the
      differences were not statistically significant. Ultrasonography enhanced
      identification of infiltrating tumor cells beyond falsely underestimated tumor
      margins as defined by T1 images. Ultrasound images helped differentiate edema as
      seen on T2 images from solid tumor and normal brain. The information gained from
      ultrasound images can be used to enhance tumor resection and improve patient
      survival and quality of life.

PMID- 8294575
TI  - Small-for-menstrual-age infants: different subgroups detected using
      individualized fetal growth assessment.
AB  - Our purpose was to study the individual fetal growth patterns of infants who were
      born small-for-menstrual-age. Growth in the second and third trimester was
      assessed in 98 small-for-menstrual-age infants, using individual fetal growth
      curves generated by the growth model: P = c(t)k+s(t). Growth indices were
      compared with those previously reported for that method in infants with normal
      growth. The small-for-menstrual-age infants were distributed into four growth
      patterns, ie, infants with either normal or decreased second-trimester growth
      indices, who, by the time of birth, succeed or fail in fulfilling their
      individual growth potential. These four growth patterns appear to be associated
      with different pathophysiological mechanisms and incidences of perinatal
      complications. Individual fetal growth assessment identifies differences in
      genetically determined growth and differentiates between fetuses who achieve
      their growth potential and those with growth failure who are at greater risk for
      fetal compromise.

PMID- 8294576
TI  - Umbilical artery Doppler flow-velocity waveforms and fetal acid-base balance in
      Rhesus-isoimmunized pregnancies.
AB  - Pulsed Doppler blood-flow velocity waveforms in the umbilical arteries, as well
      as blood gases, hematocrit, and lactate concentration in umbilical venous blood,
      were examined in 21 patients undergoing 49 cordocentesis, 34 of which were
      followed by fetal blood transfusion into the umbilical vein. The aim of the study
      was to evaluate the correlations, if any, between the Doppler indices from the
      umbilical artery (pulsatility index, resistance index, systolic/diastolic ratio)
      and the blood gas values (pO2, pCO2, O2 content, pH) and lactate content in the
      umbilical vein. The only correlation confirmed in this study was in the subgroup
      of anemic fetuses undergoing fetal blood transfusion, where correlation existed
      between A/B and the initial O2 content (r = -0.41, p < 0.02). We conclude that,
      in Rhesus-isoimmunized pregnancies, in contrast to other pregnancies, a close
      correlation does not exist between the Doppler indices in the umbilical artery
      and the fetal blood gas values.

PMID- 8294577
TI  - Umbilical artery Doppler flow-velocity waveforms in Rhesus-isoimmunized fetuses
      before and after fetal blood sampling or transfusion.
AB  - Pulsed-Doppler examinations of blood-flow velocities in the umbilical artery were
      carried out before and after 15 diagnostic cordocenteses and 34 fetal blood
      transfusions into the umbilical vein. There were decreases in the
      systolic/diastolic ratio (A/B) (p < 0.01), the pulsatility index (PI) (p < 0.05),
      and the resistance index (RI) (p < 0.01) after cordocentesis but not after fetal
      blood transfusion. There were no correlations between the initial hematocrit and
      the umbilical artery Doppler indices in the sample nor in the fetal blood
      sampling group. In the fetal blood transfusion group, on the other hand, there
      was a negative correlation between the initial hematocrit and A/B (r = -0.44; p <
      0.01) and the RI (r = -0.35; p < 0.05). The umbilical artery Doppler flow
      velocity indices did not predict the fetal hematocrit.

PMID- 8294578
TI  - Sonographic diagnosis of Neu-Laxova syndrome.

PMID- 8294579
TI  - Prenatal ultrasonic diagnosis of nonhypertrophic pyloric stenosis associated with
      intestinal malrotation.

PMID- 8294580
TI  - Ultrasound diagnosis of hydrocolpos: prenatal findings and postnatal follow-up.

PMID- 8294581
TI  - Transient unilateral ventriculomegaly: sonographic diagnosis during the second
      trimester of pregnancy.

PMID- 8294582
TI  - Pelvic kidney presenting as a tumor previa during labor: sonographic diagnosis.

PMID- 8294583
TI  - Tight nuchal coiling of the umbilical cord causing fetal death.

PMID- 8294584
TI  - Acute neutrophilic dermatosis with myeloblastic infiltrate in a leukemia patient
      receiving all-trans-retinoic acid therapy.
AB  - We report a case of leukemia-associated acute febrile neutrophilic dermatosis
      (Sweet's syndrome) that is unique because its initial histologic findings
      mimicked leukemia cutis. Otherwise, the clinical manifestations and response to
      corticosteroid therapy were typical of Sweet's syndrome. The onset of the
      dermatosis coincided with the onset of neutrophilic differentiation induced by
      single-agent leukemia therapy with all-trans-retinoic acid (ATRA). Subsequent
      exacerbation of the manifestations of Sweet's syndrome and the ultimate
      conversion of the histologic picture to the expected mature neutrophilic dermal
      infiltrate coincided with the completion of neutrophilic differentiation in the
      peripheral blood and bone marrow. The ability of immature neutrophil precursors
      to induce cutaneous lesions of Sweet's syndrome may indicate an ATRA-induced
      functional maturation that slightly precedes its effect on morphologic
      maturation. We conclude that a cutaneous infiltrate of early neutrophil
      precursors does not preclude a diagnosis of Sweet's syndrome in patients with
      acute leukemia who respond to ATRA therapy.

PMID- 8294585
TI  - Sweet's syndrome and pregnancy.

PMID- 8294586
TI  - Pseudo oral hairy leukoplakia in a renal allograft recipient.
AB  - Oral hairy leukoplakia (OHL) is a disorder of the tongue associated with Epstein
      Barr virus (EBV). OHL is seen mainly in HIV infection but is also rarely seen in
      the course of iatrogenic immunosuppression, especially in kidney transplantation;
      OHL is even more rarely seen in immunocompetent hosts. Lesions that clinically
      and histologically mimicked OHL but were not associated with EBV were recently
      characterized as pseudo hairy leukoplakia. We present such a case that occurred
      in a renal allograft recipient; light and electron microscopy,
      immunohistochemistry, and in situ hybridization were used to examine the patient
      for the presence of EBV and human papillomavirus. Two independent treatments with
      topical retinoid and oral amoxicillin resulted in complete remission. Pseudo
      hairy leukoplakia may correspond, at least in some cases, to the conditions known
      as leukoedema and white sponge nevus; the distinction of these diseases from OHL
      is of importance because OHL is a hallmark of severe immunosuppression.

PMID- 8294587
TI  - A spectrum of inflammatory metastasis to skin via lymphatics: three cases of
      carcinoma erysipeloides.
AB  - We report a case in which carcinoma erysipeloides was the first sign of the
      primary malignancy in a patient with a rare form of prostate carcinoma (mixed
      adenosquamous type) and two cases in which carcinoma erysipeloides was a marker
      of tumor recurrence in two patients with breast carcinoma. The value of
      recognizing the distinctive inflammatory manifestation of carcinoma erysipeloides
      and the significance of dermal lymphatic involvement in this form of skin
      metastasis are discussed.

PMID- 8294588
TI  - Acute hereditary coproporphyria induced by the androgenic/anabolic steroid
      methandrostenolone (Dianabol).
AB  - Acute attacks of porphyria can be induced by certain drugs. We report a case of
      acute coproporphyria induced by methandrostenolone. This is the first report of
      acute porphyria induced by an androgenic, anabolic steroid.

PMID- 8294589
TI  - Emergence of leprosy in a patient with mycosis fungoides.
AB  - A patient with mycosis fungoides that had progressed to tumor stage responded to
      chemotherapy and electron beam treatment, but 6 years later a peripheral
      neuropathy, extensive plaques, erythroderma, and enlarged pinnae containing acid
      fast organisms developed while he was being treated with photopheresis. The skin
      lesions cleared with administration of rifampin and dapsone, but a reversal
      reaction biopsy specimen showed features of both mycosis fungoides and leprosy.
      This case raises the question of whether there may be an association between
      mycosis fungoides and leprosy.

PMID- 8294590
TI  - Staphylococcal scalded skin syndrome in adults. A clinical review illustrated
      with a new case.
AB  - Staphylococcal scalded skin syndrome is rarely observed in adults; only 32 cases
      have been reported. In contrast to infant cases, the mortality rate is high. Two
      major risk factors have been identified: kidney failure and immunosuppression. In
      adults, clinical features are similar to those of the typical pediatric disease,
      but blood cultures are often positive for Staphylococcus aureus. Detection of the
      exfoliative toxin is required for diagnosis; the newborn mouse bioassay is,
      therefore, usually performed. New immunologic methods allow precise
      characterization of the toxins and oligonucleotide probes can be used for rapid
      detection of toxigenic strains. We report a case of staphylococcal scalded skin
      syndrome in an immunocompetent adult in whom blood cultures were positive; this
      is the first case in which both exfoliative toxins A and B have been identified
      in an adult.

PMID- 8294591
TI  - Necrolytic migratory erythema: a report of three cases.
AB  - Necrolytic migratory erythema (NME) is a cutaneous reaction pattern with specific
      histopathologic features that is typically associated with a functioning
      pancreatic islet cell neoplasm such as a glucagonoma. Three examples of NME, each
      associated with a different cause, are presented: glucagonoma, pancreatic
      insufficiency, and gluten-sensitive enteropathy. All three patients were
      successfully treated by surgical resection of the pancreatic tumor, total
      parenteral nutrition and pancreatic enzyme replacement, or a strict gluten-free
      diet, respectively. All remain free of skin disease more than 2 years later. Any
      patient with NME should be evaluated for glucagonoma and small bowel disease that
      may be associated with malabsorption and malnutrition.

PMID- 8294592
TI  - Cockayne syndrome in two adult siblings.
AB  - Although survival beyond the second decade is unusual in patients who have
      Cockayne syndrome, we describe two brothers with the syndrome who are 42 and 55
      years of age. Their cultured skin fibroblasts showed extreme UV sensitivity but
      had almost normal UV-induced unscheduled DNA synthesis. The patients were
      classified as genetic complementation group B after study of the recovery of RNA
      synthesis after UV irradiation of fused cells. Clinical phototesting revealed a
      reduced threshold for UVB erythema.

PMID- 8294593
TI  - Primary cutaneous myxoid melanoma: immunohistologic clues to a difficult
      diagnosis.
AB  - We describe a 25-year-old man with a primary cutaneous myxoid malignant melanoma
      and xeroderma pigmentosum. Histologically, the tumor had a lentiginous
      intraepidermal component and a dermal myxoid nodule containing fusiform cells
      with hyperchromatic nuclei and nuclear pseudoinclusions. Immunohistochemically,
      the tumor cells were positive for S-100 protein in both the epidermis and the
      dermis and did not stain with HMB-45, AE1-AE3, MNF 116, antiactin, or anti-p53
      protein. Although this tumor is rare, it should be considered in the differential
      diagnosis of cutaneous myxoid lesions.

PMID- 8294594
TI  - Epstein-Barr virus-associated lymphoproliferative disorder of granular
      lymphocytes presenting initially as cutaneous vasculitis.
AB  - Lymphoproliferative disorders of granular lymphocytes (LDGL) represent a family
      of diseases characterized by persistent granular lymphocytosis with variable
      prognosis. The Epstein-Barr virus (EBV) has been occasionally linked with the
      development of LDGL. However, cutaneous manifestations of LDGL have rarely been
      reported. One patient had cutaneous vasculitis for 10 years before a definite
      diagnosis of LDGL was made. Chronic EBV infection was documented serologically
      and EBV DNA was detected in the peripheral blood lymphocytes. EBV RNA was
      detected in the nuclei of infiltrating lymphoid cells expressing CD43 in a skin
      biopsy specimen. A cytogenetic study showed clonal chromosomal abnormalities.
      This is the first report of EBV-associated LDGL of natural killer cells with
      cutaneous manifestations.

PMID- 8294595
TI  - Disseminated pagetoid reticulosis: need for long-term follow-up.
AB  - A 54-year-old woman had an erythematous plaque on the left index finger for 2
      years. Histologically there was a dense infiltrate of atypical mononuclear cells
      in the epidermis that produced a pagetoid appearance. A diagnosis of localized
      pagetoid reticulosis was made. Three years after total removal of the finger
      lesion, erythematous plaques appeared on her left thigh, followed by the
      development of similar plaques on the right thigh and lower abdomen.
      Histologically these skin lesions had the same pagetoid appearance as the plaque
      on the finger. This suggested development of the disseminated type of pagetoid
      reticulosis, long after removal of the initial skin lesion.

PMID- 8294596
TI  - Minocycline-induced oral pigmentation.
AB  - Oral mucosal pigmentation is an infrequently reported side effect of minocycline.
      Two patients with minocycline deposition within teeth and bone, demonstrated by
      fluorescence microscopy, are described. Minocycline is the only tetracycline
      reported to cause discoloration of the oral mucosa. This may be the result of
      deposition of an insoluble degradation product of minocycline in the underlying
      bone. Pigmentation is not necessarily dose-dependent and may take months or years
      to resolve.

PMID- 8294597
TI  - Cicatrizing conjunctivitis as a predominant manifestation of linear IgA bullous
      dermatosis.
AB  - Linear IgA bullous dermatosis is an uncommon mucocutaneous autoimmune disorder
      that is distinct from dermatitis herpetiformis and bullous pemphigoid. Two
      patients who had significant conjunctival involvement but minimal skin disease
      are described. Irreversible conjunctival scarring indistinguishable from ocular
      pemphigoid developed in both patients.

PMID- 8294598
TI  - Primary anaplastic large-cell lymphoma of the skin. A case report suggesting that
      regressing atypical histiocytosis and lymphomatoid papulosis are subsets.
AB  - A patient with primary anaplastic large-cell lymphoma of the skin with
      characteristic clinical findings is described. The diagnosis was made on the
      basis of histologic and immunohistochemical findings. The phenotype of the tumor
      cells was not determined, but rearrangement of the T-cell receptor beta gene
      indicated that the tumor was of T-cell lineage. Despite high-grade malignancy of
      the tumor cells, the patient unexpectedly had a benign clinical course. The
      findings in this case suggest that regressing atypical histiocytosis and
      lymphomatoid papulosis type A are subsets of anaplastic large-cell lymphoma.

PMID- 8294599
TI  - Cutaneous meningioma underlying congenital localized hypertrichosis.
AB  - A 28-year-old man had a circumscribed hypertrichotic area on the left lumbar
      region since birth. A biopsy specimen showed numerous normal-appearing hair
      follicles and arrector pili muscles. In the subcutaneous layer a mass of dense
      collagenous connective tissue formed the background in which ill-defined foci of
      meningothelial cells in nests and pseudovascular spaces were seen. Collagenous
      structures (pseudopsammoma bodies), some of which showed calcification (psammoma
      bodies), were also seen. A diagnosis of cutaneous meningioma was made.

PMID- 8294600
TI  - An unusual case of non-Langerhans cell histiocytosis.
AB  - A 28-month-old boy had firm, red nodules for 4 months that were mostly localized
      to the face. The eruption was preceded by conjunctivitis, eyelid edema, and
      swelling of the root of the nose. He also had dyspnea, anisocoria with areflexia,
      swelling of the parotid glands, and hepatosplenomegaly. A bone marrow aspirate
      showed 25% eosinophils. A skin biopsy specimen revealed a lymphohistiocytic
      infiltrate that involved the entire dermis. Most of the cells expressed
      antimacrophage markers; S-100 was negative. Electron microscopy showed poorly
      differentiated histiocytes without any specific marker. Steroid therapy induced
      complete clearing. Two years later, after several cutaneous recurrences, the
      patient is free of disease. We believe that this case represents a nodular,
      benign non-Langerhans cell histiocytosis with cutaneous lesions that differ from
      previously described histiocytopathies.

PMID- 8294601
TI  - Chronic cutaneous dysesthesia syndrome: a psychotic phenomenon or a depressive
      symptom?
AB  - A 54-year-old woman had a 4-month history of sensitivity to all forms of light.
      Evaluation revealed no detectable abnormalities. A diagnosis of chronic cutaneous
      dysesthesia syndrome was made, and the patient experienced slow, steady
      resolution with oral pimozide. We discuss the classification, diagnostic
      categories, treatment principles, and prognosis of this disorder and summarize
      our experience with 13 other patients.

PMID- 8294602
TI  - Intraosseous chondroid syringoma of the hallux.
AB  - A 25-year-old black woman had a deformed right great toe. X-ray examination
      revealed extensive lytic change in the distal phalanx, to which technetium uptake
      was limited. The amputation specimen revealed a benign chondroid syringoma in the
      subungual tissue that penetrated and permeated the bone. Chondroid syringoma is
      rare in the foot, and we present what we believe is the first such
      immunohistochemically confirmed case involving bone.

PMID- 8294603
TI  - Milk removal in familiar and unfamiliar surroundings: concentrations of oxytocin,
      prolactin, cortisol and beta-endorphin.
AB  - Eight cows were machine milked either in an operating theatre or in their
      familiar barn. During the experiments, milk flow curves were recorded and blood
      samples were taken for determination of concentrations of oxytocin, prolactin,
      cortisol and beta-endorphin. The milking cluster was attached without udder
      preparation. After cessation of milk flow, air was blown into the vagina for 2
      min. When milk flow had stopped again, 1 i.u. oxytocin and finally 10 i.u.
      oxytocin were injected to remove the remaining milk. After the start of milking,
      oxytocin remained basal in unfamiliar, but increased in familiar surroundings.
      Therefore, during normal milking only 9% of total milk was removed in unfamiliar,
      whereas 79% was available in familiar surroundings. In response to subsequent
      vaginal stimulation in the operating theatre, oxytocin increased transiently in
      five cows and 15-71% of the milk was removed in these animals. In the other three
      cows in the operating theatre, oxytocin remained basal during vaginal
      stimulation, and no more milk was available. After injection of 1 i.u. oxytocin,
      56 and 11%, and after injection of 10 i.u. oxytocin, 13 and 8% of milk was
      removed in unfamiliar and familiar surroundings respectively. Concentrations of
      prolactin increased during the course of milking in both treatments. Premilking
      concentrations of cortisol and beta-endorphin were elevated in unfamiliar as
      compared with familiar surroundings. During the course of milking, cortisol
      increased slightly and beta-endorphin decreased in unfamiliar, whereas both
      hormones increased markedly during milking in familiar surroundings.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8294604
TI  - Yield and composition of milk from lactating mares: effect of body condition at
      foaling.
AB  - The yield and composition of milk from nursing mares were studied during the
      first 2 months of lactation in two groups of six and five saddle mares
      respectively made thin or fat before foaling, then fed ad lib. post partum. Milk
      yield did not significantly vary with body condition (16.5 and 15.4 kg/d for fat
      and thin mares respectively). Milk from fat mares had a higher fat content than
      milk from thin mares; the reverse was found for protein. The composition of milk
      fat was modified: milk of fat mares was poorer in short- and medium-chain fatty
      acids (C8-C14). Milk fat output was affected by body condition: 252 and 187 g/d
      for fat and thin mares respectively. This can be explained by a difference in
      lipid mobilization, as shown by variations in non-esterified fatty acids.

PMID- 8294605
TI  - Discovery of an ovine alpha S2-casein variant.
AB  - A novel ovine alpha S2-casein variant has been detected using discontinuous
      polyacrylamide gel electrophoresis at alkaline pH, two dimensional
      electrophoresis and immunoblotting. It is characterized by a greater negative net
      charge and a lower isoelectric point compared with the most common ovine alpha S2
      casein variant. The phenotypic frequency in the Manchega breed is 5.5%.

PMID- 8294606
TI  - Comparative study of the separation of casein from bovine, ovine and caprine
      milks using HPLC.
AB  - The separation of cows', sheep's and goats' milk casein components by HPLC on a
      strong anion-exchange (P.L-SAX 8 mu 1000A) column is described. During HLPC,
      whole caseins of the three kinds of milk behaved differently from conventional
      separations. The casein components of the three kinds of milk were well resolved
      under the chromatographic conditions used. HPLC resolved the kappa-caseins better
      than did ion-exchange chromatography on DEAE cellulose, and was particularly
      efficient in the case of goats' milk. Goats' and sheep's milks had almost similar
      chromatographic profiles but these differed considerably from that of cows' milk.
      Caseins from the sheep and the goat were also similar in that a shallower NaCl
      gradient was required for the separation of casein components than for cows'
      milk.

PMID- 8294607
TI  - Effect of the A and B variants of both alpha s1- and kappa-casein on bovine
      casein micelle solvation and kappa-casein content.
AB  - Casein micelle solvation, a micelle characteristic that is sensitive to many
      factors, has been measured by a centrifugation technique at 30 degrees C for a
      series of uncooled fresh skim milks at pH 6.3, 6.6, 6.9 and 7.1. The relative
      alpha s-(alpha s1-plus alpha s2-), beta- and kappa-casein contents of all
      centrifuge pellets and supernatants were determined by a standardized
      electrophoretic method. The calcium and phosphate contents of a number of the
      pellets and milk samples were also determined. Solvation of micelles from milks
      with various genetic variants of beta-lactoglobulin (A and B), alpha s1-casein (A
      and B) and kappa-casein (A and B) was often found to be lower for milks
      containing either the B variant of alpha s1-casein or the A variant of kappa
      casein. It was also found that these two variant caseins were associated with a
      lower kappa-casein. It was also found that these two variant caseins were
      associated with a lower kappa-casein content of the milks and the micelles, which
      is consistent with the lower solvation as kappa-casein is associated with smaller
      micelle size and greater solvation. The solvations also seemed to increase during
      the lactation period. It is possible that some of the other features of milk and
      its products that have been ascribed to the differences in functional character
      between the A and B variants of alpha s1-casein may be partly caused by the
      increased level of kappa-casein. The reason for the association of the A variant
      of alpha s1-casein with higher concentrations of kappa-casein (and micelle
      solvation) is not obvious but possibly the haplotype alpha s1-casein A, beta
      casein A1, kappa-casein A contains a controlling sequence in the chromosomal DNA
      that enhances expression of the kappa-casein gene.

PMID- 8294608
TI  - Phosphorylation, glycosylation and amino acid sequence of component PP3 from the
      proteose peptone fraction of bovine milk.
AB  - Component PP3 is a phosphorylated glycoprotein with an apparent molecular mass of
      28 kDa isolated from the proteose peptone fraction of bovine milk. The function
      of the protein is not known. The primary structure has been determined and shown
      to contain 135 amino acid residues (EMBL accession no. P80195). It was
      phosphorylated at Ser29, Ser34, Ser38, Ser40 and Ser46. Two O-linked carbohydrate
      groups were found at Thr16 and Thr86, while one N-linked carbohydrate group was
      present at Asn77. Thr16 was only approximately 50% glycosylated. The amino sugar
      detected by the amino acid analyser at Thr86 was mainly galactosamine but a small
      amount of glucosamine was also present. The amino sugars found in the
      carbohydrate group linked to Asn77 were both glucosamine and galactosamine. A
      fragment of PP3 has been isolated from milk and shown to correspond to residues
      54-135. This fragment was probably generated by plasmin hydrolysing the Arg53
      Ser54 bond.

PMID- 8294609
TI  - Toxin production by Bacillus cereus in dairy products.
AB  - Spores of a known toxigenic and psychrotrophic dairy isolate of Bacillus cereus
      (HRM 44) were unable to grow and produce diarrhoeagenic toxin at 6 degrees C in
      creams and dairy-based products. These findings suggest that the production of B.
      cereus diarrhoeagenic toxin is unlikely to occur in creams and dairy-based
      products maintained within the cold chain. Growth and toxin production were
      readily demonstrated in creams and some desserts stored at 21 degrees C. Growth
      in creams was associated with obvious spoilage. However, in the flavoured
      desserts, spoilage was not always obvious before significant growth of B. cereus
      and toxin production had occurred. Dairy desserts with high sugar content and/or
      low pH did not support toxin production and these findings are discussed.

PMID- 8294610
TI  - Influence of pH and sugars on the growth and production of diarrhoeagenic toxin
      by Bacillus cereus.
AB  - Broth cultures supplemented with high levels of sugars, particularly glucose at >
      50 milligrams, did not support diarrhoeagenic toxin production by psychrotrophic
      Bacillus cereus despite growth to high counts (approximately 10(7)/ml) over a 4 d
      period of incubation at 21 degrees C. In contrast, starch levels of 10 and 50
      milligrams actually enhanced toxin production. Toxin production was also affected
      by pH levels of broth cultures, and was concomitant with alterations in bacterial
      growth. These findings help to explain variations in toxin levels previously
      found in some dairy desserts, which were thought to be associated with pH and
      sugar content (Sutherland, 1993).

PMID- 8294611
TI  - Composition and characteristics of camel milk.

PMID- 8294612
TI  - Saliva composition in Indian children with chronic protein-energy malnutrition.
AB  - The composition of paraffin-stimulated and unstimulated whole saliva was compared
      between two groups of 8-12-year-old Indian children-one group with severe to
      moderate chronic protein-energy malnutrition (PEM group) and an age- and sex
      matched control group with normal protein status or mild PEM. The classification
      of PEM was based on anthropometric measurements compared with Indian standards.
      Stimulated saliva was analyzed for the following variables: electrolytes (Na+,
      K+, Ca2+, Cl-, and PO4(3-)), total protein, hexosamines, fucose, sialic acid, and
      amylase. Unstimulated saliva samples were analyzed for total protein, salivary
      and myeloperoxidase, thiocyanate, lactoferrin, lysozyme, a bacteria-agglutinating
      protein (BAGP), total IgG, total IgA, and specific anti-S. mutans IgA. The
      results show that the PEM group had a reduced secretion rate of stimulated but
      not unstimulated saliva. Further, the Ca2+ and Cl- concentrations in stimulated
      saliva were significantly lower in the PEM group compared with the control group,
      but the other electrolyte levels were similar. No differences were found in total
      protein concentration or glycoprotein bound carbohydrates in stimulated saliva
      between the two groups, but the quantity of total protein secreted per min was
      reduced by 20% in the PEM group. Significantly lower levels of lactoferrin, BAGP,
      and anti-S mutans IgA were found in unstimulated saliva from children in the PEM
      group, but significantly higher levels of total IgG. We conclude that children
      with severe or moderate PEM, who have reduced secretion rate, buffer capacity,
      lower Ca2+, and protein secretion in stimulated saliva, also have impaired
      immunological and agglutinating defense factors in unstimulated saliva.

PMID- 8294613
TI  - The balance between inclusion and exclusion.

PMID- 8294614
TI  - Prevalence of subjective feelings of dry mouth in the elderly.
AB  - Dry mouth is a common disorder in elderly individuals. It is not, however,
      necessarily related to decreased salivary flow rate, since subjective feelings of
      oral dryness have also been found in those with normal flow rates. The aim of
      this study was to examine in elderly individuals the prevalence of subjective
      complaints related to dry mouth, and their association with salivary flow rates
      and the use of systemic medication. In 1990 and 1991, 368 elderly inhabitants of
      Helsinki, Finland, had their oral health status examined. In addition to the
      clinical examination, 341 subjects were interviewed regarding different oral and
      non-oral complaints related to dry mouth. Findings showed that 46% (n = 158) of
      the subjects had noticed subjective symptoms of dry mouth. Continuous oral
      dryness was reported by 12% (n = 40) of the subjects, 6% of the men and 14% of
      the women (p < 0.05). In these 40, the oral and non-oral symptoms were more
      frequent in subjects reporting continuous dry mouth compared with controls.
      Continuous dry mouth was clearly associated with the female gender, with mouth
      breathing and with the use of systemic medications.

PMID- 8294615
TI  - Effects on whole saliva of chewing gums containing calcium phosphates.
AB  - To evaluate chewing gums as a vehicle to increase salivary mineral saturation
      levels and enhance salivation, monocalcium phosphate monohydrate (MCPM) and an
      equimolar mixture of tetracalcium phosphate (TTCP) with dicalcium phosphate
      anhydrous (DCPA) were chosen as experimental chewing gum additives. Each of eight
      subjects chewed a commercial sugarless bubble gum (control) for 16 min or the
      same gum to which 5 wt% of MCPM or the TTCP-DCPM mixture had been added. The
      saliva samples collected every 2 min were analyzed for weight, pH, and total
      calcium (Ca) and phosphate (P) concentrations. Both experimental gums were found
      to increase significantly the Ca and P concentrations of saliva during the 16
      minute period even more than with a previously evaluated gum that contained
      dicalcium phosphate dihydrate. The degree of saturation of tooth mineral was
      significantly increased by both experimental gums, with the greater increase
      being produced by the TTCP-DCPA gum. The MCPM gum produced a significantly
      greater saliva flow and a lower salivary pH than did the control and TTCP-DCPA
      gums. The results suggest that the experimental gums may be useful for promoting
      remineralization in general and for inducing salivation in xerostomic patients.

PMID- 8294616
TI  - Release of elements due to electrochemical corrosion of dental amalgam.
AB  - The corrosion pattern of dental amalgam in aqueous media was interpreted
      theoretically by means of log(ai/a(ref))-pe diagrams. The definitions on which
      the diagrams were based were given, and their features were described. All
      sparingly soluble compounds which were expected to be formed in reactions with
      the solvents considered were listed. All the corrosion products reported in the
      current literature were found to be formed, and the conditions for their
      formation were established. It emerged that it was necessary to exclude other
      sparingly soluble compounds with theoretically might be formed. Two compounds,
      CuSCN and AgSCN, which have not been reported previously were found to be
      possible corrosion products. Corrosion products containing mercury compound
      cannot be formed on amalgam restorations with no metallic contact with other
      materials.

PMID- 8294617
TI  - In vitro bond strengths and SEM evaluation of dentin bonding systems to different
      dentin substrates.
AB  - In comparison to enamel, bonding to normal dentin is a greater challenge because
      of its organic constituents, fluid-filed tubules, and variations in intrinsic
      composition. Bonding to sclerotic dentin is even more difficult. To evaluate the
      shear bond strengths of four adhesive systems to dentin substrates with different
      levels of mineralization, 120 extracted human teeth were randomly assigned to
      three groups (n = 40). After mid-coronal dentin was exposed, groups of specimens
      were artificially hypermineralized by immersion in a remineralizing solution,
      demineralized by means of an acetic acid demineralizing solution, or stored in
      distilled water to model sclerotic, carious, and normal dentin, respectively.
      Resin composite was bonded to dentin by use of commercial adhesive systems. After
      the specimens were thermocycled, shear bond strengths were determined in an
      Instron universal testing machine. Dentin substrates and resin/dentin interfaces
      were examined by SEM. For each adhesive system, the mean shear bond strength to
      normal dentin was significantly higher than that to either of the other
      substrates. Shear bond strengths to hypermineralized dentin were significantly
      higher than those to demineralized dentin with all adhesives except Prisma
      Universal Bond 3.

PMID- 8294618
TI  - Effects of the beta-adrenoceptor antagonists atenolol and propranolol on human
      parotid and submandibular-sublingual salivary secretion.
AB  - The aim of the study was to evaluate the effects of a beta 1-selective (atenolol
      50 mg q.d.) and a non-selective (propranolol 80 mg b.i.d.) beta-adrenoceptor
      antagonists on human stimulated parotid and submandibular-sublingual (SM-SL)
      gland secretion. A randomized double-blind, placebo-controlled cross-over ("Latin
      square") design was used in 19 healthy male volunteers. Stimulated parotid and SM
      SL saliva were sampled immediately before and 7 days after the start of each
      treatment period. Stimulation of salivary secretion was achieved by use of a 3%
      citric acid solution. Plasma concentrations of propranolol and atenolol were
      determined from blood samples. The salivary secretion of both glands was assessed
      for flow rate, amylase, lysozyme, and salivary peroxidase activity and for
      concentrations of total protein, hexosamine, sialic acid, Ca2+, Cl-, K+, Mg2+,
      Na+, and PO4(3-). In both parotid and SM-SL secretions, the total protein and
      phosphate concentrations and amylase activity were significantly decreased during
      the two active treatment periods. In SM-SL gland secretion, there were
      significant changes in potassium and calcium concentrations during active
      treatment as compared with baseline, with potassium showing a decreased and
      calcium an increased concentration. During atenolol treatment, salivary
      peroxidase activity decreased significantly in SM-SL secretion. In parotid
      secretion, the hexosamine/total protein ratio decreased and the sialic
      acid/hexosamine ratio increased during atenolol treatment, which may indicate an
      effect on protein synthesis. No significant effects on salivary secretion rates
      were disclosed.

PMID- 8294619
TI  - Deformation of the human mandible during simulated tooth clenching.
AB  - Localized corpus and dental arch distortions measured directly on human and
      animal mandibles suggest complex deformation patterns at other mandibular sites
      during functional loading. To describe these, we simulated selected static bites
      on a three-dimensional finite element computer model of the human jaw. Five
      clenching tasks were modeled: intercuspal position, left group function, left
      group function plus balancing contact, incisal clenching, and right molar
      clenching. Under conditions of static equilibrium and within the limitations of
      the current modeling approach, the human jaw deforms elastically during
      symmetrical and asymmetrical clenching tasks. This deformation is complex, and
      includes the rotational distortion of the corpora around their axes. In addition,
      the jaw also deforms parasagittally and transversely. The degree of distortion
      depended on each clenching task, with actual deformations being relatively small
      and ranging from 0.46 mm to 1.06 mm for the tasks modeled when all sites were
      taken into account. The predicted overall narrowing of the dental arch is
      consistent with clinical reports in the literature during similar, although not
      identical, static jaw function. The predicted regional deformations of the upper
      condylar surfaces imply differential loading at their upper surfaces. Although
      still constrained to forceful static biting conditions, the simulated mandibular
      and dental arch distortions should be taken into consideration in the design and
      testing of prosthetic devices in the lower jaw.

PMID- 8294620
TI  - 3-D force and moment analysis of repulsive magnetic appliances to correct
      dentofacial vertical excess.
AB  - Repulsive magnetic appliances can intrude posterior teeth, but create a lateral
      shift of the mandible and also decrease in force as the mouth opens. To model
      their optimal use, the 3-D spatial force/displacement (F/D) and
      moment/displacement (M/D) diagrams of four magnetic repulsive appliances in
      diverse overlapping arrangements were characterized and compared. In this
      orthodontic measurement and simulation system, only the medial eccentric magnetic
      arrangement, of the four compared, partially met the criteria of an optimal
      repulsive force system, i.e., keeping a constant intruding force and excluding
      shearing force. The moment analysis found that eccentric arrangements, however,
      developed high Z-moment. Thus, a perplexing point was reached where the force
      analysis favored medial centric arrangement and the moment analysis favored
      centric arrangement. When the gap between juxtaposed magnets increased over 2 mm,
      the repulsive force declined and the attractive force was favorably eliminated.
      At gap distances of 3 to 6 mm, the intrusive force was almost constant. These
      data suggest that centric arrangement is indicated clinically when the gap is
      minute and Muller prongs are used to prevent deleterious lateral shearing forces.

PMID- 8294621
TI  - Pyrethroid resistance in German cockroaches (Dictyoptera: Blattelidae):
      resistance levels and underlying mechanisms.
AB  - Thirty strains of Blattella germanica (L.) reported to be pyrethroid resistant
      were collected from three continents. Greater than 2-fold resistance to the
      pyrethroids cyfluthrin, fenvalerate, cypermethrin, and lambda cyhalothrin
      appeared in 15 of these strains. Twelve of these strains were also resistant to
      chlorpyrifos and propoxur. All the field strains tested were heterogeneous with
      regard to resistance. Possible resistance mechanisms detected in these
      populations included elevated levels of cytochrome P450, general esterase and
      glutathione S-transferase, and nerve insensitivity (kdr-type resistance). The
      elevated esterases and oxidase-based resistance were the most prevalent; 11 and
      10 strains, respectively, had evidence of these mechanisms. Resistance was
      synergized by piperonyl butoxide in some strains. In some strains, elevated
      esterases, although present, were primarily correlated with organophosphate
      resistance. Pyrethroid insecticides may still be effective against many of these
      populations because of the low levels of resistance detected. However, potential
      exists for more serious resistance problems to develop if only pyrethroids are
      used. Because many of these strains are already resistant to organophosphorus and
      carbamate insecticides, prospects for the future chemical control of these
      populations must be carefully considered.

PMID- 8294622
TI  - Decline of pyrethroid resistance in the absence of selection pressure in a
      population of German cockroaches (Dictyoptera: Blattellidae).
AB  - The level of resistance to seven pyrethroids was followed in a laboratory
      selected population of Blattella germanica (L.) for 15 generations, during which
      time it was not exposed to any insecticide. As estimated by LT50 resistance
      ratios (RRs), resistance declined in a stepwise manner to preselection levels
      with all of the pyrethroids except pyrethrins. I also compared the levels of
      resistance as indicated by RRs and by gene frequency (GF) estimates. Results
      showed that GF estimates provide a more precise indication of the changes in
      resistance that occur over time than do RRs alone, especially when combined with
      RR and end-point mortality data. I discuss my results from the standpoints of the
      number of genetic mechanisms involved in pyrethroid resistance in this insect,
      and what the declines in resistance mean for future cockroach control.

PMID- 8294623
TI  - Non-invasive ventilation: practical issues.

PMID- 8294624
TI  - Minidose inhaled nitric oxide: less is better.

PMID- 8294625
TI  - Enteral nutrition in the critically ill patient: a critical review of the
      evidence.
AB  - OBJECTIVE: To examine the relationship between enteral nutrition (EN) and
      infection in the critically ill. SETTING: Computerized search of published
      research and review of relevant reference lists. STUDY SELECTION: 151 citations
      were reviewed and 39 articles met selection criteria. Primary studies were
      included if they evaluated EN in critically ill humans and its effect on
      infectious morbidity and mortality. MEASUREMENTS AND RESULTS: Relevant data were
      abstracted on the timing and impact of EN on morbidity, the optimal route of
      administration, composition and pH of EN, and bacterial contamination of EN. The
      evidence from human studies that EN, particularly early EN, results in reduced
      septic morbidity as compared to parenteral nutrition is limited to small,
      unblinded studies with non-rigorous definitions of pneumonia. There is no
      evidence to support a preference of feeding into the stomach versus the small
      bowel. The addition of fish oil, arginine, glutamine and fiber to enteral feeds
      has a variable impact on survival in animal models; there are no trials in
      critically ill patients that demonstrate a reduction in infectious morbidity and
      mortality. Acidification of enteral nutrition results in decreased bacterial
      colonization of the stomach in critically ill patients. Bacterial contamination
      of enteral nutrition is an important source of infection. CONCLUSIONS: Evidence
      from experimental data in critically ill patients suggests that enteral nutrition
      may have a favourable impact on gastrointestinal immunological function and
      infectious morbidity.

PMID- 8294626
TI  - Long-term inhalation with evaluated low doses of nitric oxide for selective
      improvement of oxygenation in patients with adult respiratory distress syndrome.
AB  - OBJECTIVE: To evaluate the lowest dose of inhaled nitric oxide (NO) in patients
      with adult respiratory distress syndrome (ARDS), which is able to improve
      arterial oxygenation more than 30% compared to baseline data. DESIGN:
      Prospective, clinical study. SETTING: Anesthesiological ICU in a university
      hospital. PATIENTS: 3 consecutive patients with severe ARDS according to clinical
      and radiological signs. INTERVENTIONS: Pressure-controlled ventilation with
      positive end-expiratory pressure of 8-12 cm H2O. Inhalation of NO was performed
      with a blender system and a Servo 300 ventilator. The lowest effective NO dose
      was defined by titrating the inspiratory NO dose until reaching a 30% improvement
      of PaO2/FiO2. This dose was used for the following continuous long-term NO
      inhalation; controls of efficacy by investigation of hemodynamics and blood gas
      exchange were performed initially and 2 times per patient after intervals of 3-5
      days. MEASUREMENTS AND RESULTS: Initial NO concentrations were found to be
      effective at 60, 100, and 230 parts per billion (ppb). In all measurements,
      arterial oxygenation was found to be elevated by NO inhalation with the initially
      evaluated dose compared to baseline data; in parallel, the venous admixture
      (Qva/Qt) was reduced. The O2 delivery increased, although O2 consumption and
      hemodynamics did not change. In 1 patient, interruption of NO inhalation caused
      remarkable increase of pulmonary resistance. CONCLUSIONS: The improvement of
      oxygenation by NO inhalation in ARDS does not require reduction of pulmonary
      resistance and can be performed using low doses in the ppb range, which has to be
      considered as probably non-toxic.

PMID- 8294627
TI  - Non-invasive modalities of positive pressure ventilation improve the outcome of
      acute exacerbations in COLD patients.
AB  - OBJECTIVE: 1) To compare the clinical usefulness of both non-invasive pressure
      support ventilation (NPSV) and non-invasive intermittent positive pressure
      ventilation in assist-control (A/C) mode (NIPPV) in chronic obstructive lung
      disease (COLD) patients with acute hypercapnic respiratory failure: 2) to compare
      retrospectively the usefulness of non-invasive mechanical ventilation (NMV) with
      standard medical therapy alone. DESIGN: Prospective randomized retrospective
      study. SETTING: 2 Respiratory intermediate intensive units. PATIENTS: 29 COLD
      patients (age: 62 +/- 8 years) with chronic respiratory failure were hospitalized
      in a department for rehabilitation during acute relapses of their disease. They
      were transferred to our intermediate intensive care unit (IICU) and submitted
      randomly to either NPSV (16 patients) or NIPPV (13 patients). MEASUREMENTS AND
      RESULTS: Blood gas analysis, dynamic flows, clinical variables, success rate,
      time of ventilation, side effects and subjective score of compliance to therapy.
      Therapy was considered successful when endotracheal intubation was avoided and
      patients were returned to their condition prior to exacerbation. No statistically
      significant difference was found between NPSV and NIPPV in success rate (NPSV
      87.5%; NIPPV 77%) or in time of ventilation (NPSV: 69 +/- 49; NIPPV: 57 +/- 49
      h). A better compliance to non-invasive mechanical ventilation (NMV) was found in
      NPSV patients than in NIPPV patients; side effects were observed less frequently
      in the NPSV group. Comparison of the success rate of NMV was retrospectively
      performed with 35 control COLD patients with chronic respiratory insufficiency
      who had undergone an acute relapse of their disease in the 2 years preceding the
      institution of the IICU and had been treated with oxygen and medical therapy
      alone. Patients submitted to NMV showed a greater success rate than control (82
      versus 54%) after a period of ventilation ranging from 4-216 h. CONCLUSION: Non
      invasive mechanical ventilation performed either by NPSV or NIPPV may improve the
      outcome of acute exacerbations of COLD, as compared to medical therapy alone.
      NPSV seems to be more acceptable to patients in comparison with NIPPV.

PMID- 8294628
TI  - Pressure support ventilation via face mask in acute respiratory failure in
      hypercapnic COPD patients.
AB  - OBJECTIVE: To test whether non-invasive ventilation via facial mask could reduce
      the need for tracheal intubation when mechanical ventilation must be initiated in
      COPD patients. DESIGN: Open prospective interventional study. SETTING: General
      Intensive Care Service of a County Hospital. PATIENTS: We have studied 12 COPD
      patients during 14 episodes of acute exacerbation of chronic respiratory failure
      who failed to improve with intensive medical therapy and showed impairments in
      severe respiratory acidosis and/or hypercapnic encephalopathy leading their
      attending physicians to order mechanical ventilation. INTERVENTIONS: In these
      circumstances, a trial of pressure-support (PS) ventilation (Servo Ventilator
      900C) via facial mask Vital Signs Inc.) was performed. The level of pressure
      support was adjusted to obtain a tidal volume > 400 ml. If the patient
      deteriorated, tracheal intubation and standard mechanical ventilation were
      performed. MEASUREMENTS AND RESULTS: Measurements are presented as means +/- SEM.
      A pressure-support level of 14 +/- 3 cmH2O was used during a period of 8 +/- 4 h.
      Low levels of external PEEP were used in 4 patients, while it generated excessive
      leaks in the others. Significant differences (p < 0.05 ANOVA for repeated
      measures) in data obtained on admission, when patients deteriorated and after
      pressure support was administered were only observed in PaCO2 (68 +/- 3 versus 92
      +/- 3 versus 67 +/- 3 mmHg), arterial pH (7.27 +/- 0.03 versus 7.19 +/- 0.02
      versus 7.31 +/- 0.01). SaO2 (60 +/- 4 versus 86 +/- 3 versus 92 +/- 1%) and
      respiratory rate (35 +/- 2 versus 32 +/- 2 versus 23 +/- 1 breaths.min-1). Three
      patients needed intubation and one of them died in the ICU. CONCLUSION: Non
      invasive ventilation (pressure-support) via face mask may reduce the need for
      tracheal intubation in the severe hypercapnic failure of COPD patients.

PMID- 8294629
TI  - Use of heat and moisture exchanging (HME) filters in mechanically ventilated ICU
      patients: influence on airway flow-resistance.
AB  - OBJECTIVE: To investigate the flow-resistance of a new generation of Heat
      Moisture Exchanging Filters (HME filters) during 24 h of clinical use. DESIGN:
      Before-after trial. SETTING: A general Intensive Care Unit of a university
      hospital. PATIENTS: A consecutive series of 96 patients undergoing mechanical
      ventilation for respiratory insufficiency of various etiology and severity.
      METHODS: The characteristics of the secretions collected by tracheal suctioning
      and the pressure/flow relationship of the HMEs before and after 24 h of clinical
      use were analyzed. RESULTS: The resistance of the HMEs when dry was 2 hPa/l.s,
      and it increased to a maximum of 1 hPa/l.s in 83% of the patients after 24 hours;
      in four patients with particularly heavy secretions HME resistance was 4-5
      hPa/l.s. There were no significant modifications of the secretions within the
      investigation period, excluding, in particular, an increase in density with
      consequent tracheal tube obstruction. CONCLUSION: The gas conditioning efficiency
      and design performance of the tested HMEs did not create a significant obstacle
      to airflow medium term mechanical ventilation; however, these devices should be
      cautiously used in patients with heavy bronchial secretions.

PMID- 8294630
TI  - High-dose intravenous magnesium sulfate in the management of life-threatening
      status asthmaticus.
AB  - In severe status asthmaticus basic medical treatment often fails to improve the
      patient's condition. Mechanical ventilation in this situation is associated with
      a high incidence of serious complications. After the bronchodilating effect of
      moderate-dose magnesium sulfate in asthmatic patients had been demonstrated in
      previous studies we treated five mechanically ventilated patients with refractory
      status asthmaticus successfully with high dosages of MgSO4 IV (10-20 g within 1 h
      depending on the bronchodilating effect). MgSO4 resulted in a significant
      decrease of peak airway pressure (43.0 +/- 6.8 to 32.0 +/- 8.0 cmH2O) and
      inspiratory flow resistance (22.7 +/- 7.0 to 11.9 +/- 6.0 cmH2O.l-1.s-1) within 1
      h. The resulting serum magnesium levels after one hour were up to threefold of
      the normal serum levels. Although a maintainance dose of 0.4 g/h had been
      administered continuously during the following 24 h serum magnesium decreased
      towards normal values within this time. The only relevant side-effect was a mild
      to moderate arterial hypotension in two of the five patients during the high dose
      administration period of MgSO4 which responded readily to dopamine treatment.

PMID- 8294631
TI  - Benign stricture of the extra-hepatic bile duct following hepatectomy for
      traumatic hepatic rupture.
AB  - Benign biliary stricture developing after hepatectomy is uncommon and its
      management remains controversial. We experienced a case of biliary stricture
      following hepatectomy for traumatic hepatic rupture, which was successfully
      treated with percutaneous transhepatic dilatation. Percutaneous transhepatic
      dilatation may be considered as one of the options in the treatment of
      anatomically complicated cases.

PMID- 8294632
TI  - Heparin-associated thrombocytopenia syndrome: an underestimated etiology of
      adrenal hemorrhage.
AB  - A 74-year-old man developed bilateral arterial thrombosis of the lower limbs
      related to heparin-associated thrombocytopenia syndrome (HATS). On day 4 after
      thrombectomy of both limbs, abdominal pain, fever, hypotension, abdominal
      tenderness appeared. Acute acalculous cholecystitis was suspected and
      cholecystectomy was carried out although the gallbladder was not imflamed. Later
      on, hyponatremia in addition to the aforesaid signs suggested the diagnosis of
      adrenal insufficiency. Diagnosis was confirmed by low cortisol and aldosterone
      plasma concentration and by CT scan, which showen two enlarged adrenal glands.
      HATS might explain two unexpected facts: occurrence of adrenal hemorrhage during
      heparin therapy with coagulation tests within the therapeutic range and
      paradoxical thrombosis in the central vein of adrenal gland. HATS must be
      regarded as one cause of adrenal hemorrhage necrosis.

PMID- 8294633
TI  - Bedside measurement of intra-abdominal pressure (IAP) via an indwelling naso
      gastric tube: clinical validation of the technique.
AB  - OBJECTIVES: To compare measurements of intraabdominal pressure (IAP) via a naso
      gastric tube with the previously validated technique of IAP measurement via a
      urinary bladder catheter. To examine an association between elevated IAP and
      oliguric acute renal failure. DESIGN: Simultaneous paired measurements of gastric
      and urinary bladder pressures in supine patients. SETTING: The general intensive
      care units of two London hospitals. PATIENTS: 141 Paired measurements of
      intragastric and urinary bladder pressures were obtained in 26 general intensive
      care patients. MEASUREMENTS AND RESULTS: With the patient lying supine, 50 ml of
      sterile water were instilled via manometer tubing into the stomach and bladder
      following drainage of each viscera. The mid-axillary line was used as the zero
      reference, and cavity pressures noted in centimeters of water (cmH2O) at end
      expiration. The results were compared using the technique of Bland and Altman.
      RESULTS: Gastric pressure may be approximately 2.5 cmH2O above or below urinary
      bladder pressure. Manometric measurement of the gastric pressure via a naso
      gastric tube provides a simple, reliable, non-invasive technique of IAP
      measurement. IAP should be regularly monitored in patients with abdominal
      distension at risk of acute renal failure.

PMID- 8294634
TI  - Achromobacter xylosoxidans (Alcaligenes xylosoxidans subspecies xylosoxidans)
      bacteremia after liver transplantation.

PMID- 8294635
TI  - Shoshin beriberi in a patient with human immunodeficiency virus infection.

PMID- 8294636
TI  - And still the children die.

PMID- 8294637
TI  - Nursing history and controversial topics.

PMID- 8294638
TI  - Global perspectives of health care reform.

PMID- 8294639
TI  - A plea for revisiting values in nursing and health care.

PMID- 8294640
TI  - Meeting the demands for advanced practice nurses.

PMID- 8294641
TI  - Essentials of doctoral education: organization of program around knowledge areas.
AB  - This article presents a case study describing how one nursing doctoral program
      faculty has identified, organized, and taught the disciplinary knowledge
      component of the curriculum. Three foci were chosen: health promotion and risk
      reduction; acute, critical, and long-term care; and systems. Faculty groups
      designed each focus to capitalize on current faculty research strengths and did
      not use a formalized knowledge structure a priori. Scholarship content and sample
      courses are described. Factors affecting implementation included providing
      students with choice; a mixture of full-time and part-time students; little
      interchangeability of faculty in courses; balancing doctoral teaching with
      teaching at other levels; advisement issues; a lengthy formal curriculum approval
      process; and highly specific needs of individual students. Initial reflection
      shows the possibility of integrating the research methods content into the
      disciplinary courses in light of their interdependence; help gained through the
      process in achieving clarity about what the school wishes to be known for; the
      necessity of a critical mass of faculty with active research programs along with
      commitment to program enrichment; the role of the foci in providing intellectual
      sustenance and mutual faculty mentorship; and concern about the inability to fit
      of some faculty.

PMID- 8294642
TI  - Funding and socialization in the doctoral program at the University of Wisconsin
      Madison.
AB  - This article describes the model of funding and socializing doctoral students
      that has been used by the School of Nursing at the University of Wisconsin
      Madison. The goal of the Madison program is to educate persons who are capable of
      conducting research that will contribute to the scientific knowledge base of
      nursing. This goal is accomplished through immersing students in all aspects of
      the research process. Critical components of socialization are described. These
      include the mentor-student relationship, participation in a research group, and
      participation in informal discussions of faculty and students' research programs.
      The importance of establishing funding mechanisms and faculty work loads that
      support socialization is also emphasized.

PMID- 8294643
TI  - Master's degree nursing education: state of the art.
AB  - This study examines the state of the art in master's nursing education in the
      United States in light of projected national trends in the health care delivery
      system. The specific questions addressed are: What are the general
      characteristics of master's programs, including admission requirements and
      prerequisites, program requirements, major and minor areas of clinical
      concentration, functional role preparation, and career mobility options? What is
      the curricular organization, particularly with respect to required core courses?
      Is there a difference between master's programs in schools with a doctoral
      program in nursing and those with master's programs only? Is there a difference
      between master's programs with public support and master's programs with private
      support? Data were collected from 175 accredited master's programs in 1990. Study
      results and the projected trends derived from Nursing's Agenda for Health Care
      Reform, Healthy People 2000: National Health Promotion and Disease Prevention
      Objectives, and Healthy America: Practitioners for 2005 provide the foundation
      for recommendations. Recommendations are organized around communication and
      curricular issues that master's nursing education needs to address as the
      profession approaches the 21st century.

PMID- 8294644
TI  - National Council Licensure Examination success: accurate prediction of student
      performance on the post-1988 examination.
AB  - This study was designed to identify variables that might be used as predictors
      for success on the post-1988 National Council Licensure Examination (NCLEX) and
      to identify those students at risk of failing the examination. The convenience
      sample consisted of 257 graduates of a baccalaureate nursing program from 1988 to
      1990. The investigators examined 15 variables to determine their predictive value
      for NCLEX success. Grades in the first senior level nursing course and graduation
      grade point index were the two best predictors. Results of the discriminant
      analyses identified seven significant predictor variables leading to successful
      classification of 86 per cent of students at the end of the junior year, 88 per
      cent during the senior year, and 91 per cent by the time of graduation. Findings
      from this study indicate that reasonably accurate predictive data on individual
      student performance is available by the end of the junior year, allowing faculty
      to begin interventions for at-risk students. The greater precision of prediction
      during the senior year and at graduation provides direction for later remediation
      to increase the probability of passing the NCLEX.

PMID- 8294645
TI  - Nursing service data for research in patient care.
AB  - Nursing service records from the nontechnical medical care program, an Oklahoma
      statewide Medicaid long-term community care program, provided a unique data base
      to gather information for research purposes and program improvement. This article
      describes the process of developing a data collection (coding) form to extract a
      minimum data set and a method of training lay coders to use the form. Inherent
      problems associated with this process from the beginning to the end are also
      shared.

PMID- 8294646
TI  - A behavioral inventory for professionalism in nursing.
AB  - The purpose of this article is to describe the development of an evaluative
      behavioral inventory based on Miller's Model for Professionalism in Nursing and
      to report results of an investigation of registered nurses (RNs) in eight western
      states. The Professionalism in Nursing Inventory was mailed to 1,600 computer
      generated randomly selected names of RNs, resulting in 515 complete and usable
      inventories. Results indicated that the majority of respondents demonstrated
      professional behaviors in continuing education activities, autonomous quality
      assurance participation, community service, and a theory-based nursing practice.
      Behaviors not considered a priority with a majority of the respondents were
      publication, research activities, and participation in the constituent state
      organizations of the American Nurses Association. Approximately 4 per cent of the
      respondents commented that employing agencies and administrative (nursing)
      personnel were concerned with output, not professional behaviors. More than 91
      per cent of these respondents believed that a self-evaluative instrument for
      professional behaviors was necessary and that the tool should be developed by
      nurses.

PMID- 8294647
TI  - Perspectives on critical and feminist theory in developing nursing praxis.
AB  - Critical theory and feminist theory offer to nurses points from which to approach
      change as nursing struggles for autonomy, accountability, and control over the
      profession. Nurses need to critically examine the forces that influence the
      profession as well as the individual and group identities of nurses. These
      theoretical frameworks, together with historical inquiry, are particularly
      valuable tools for nurses to use to remain strong and vital participants in
      shaping the profession as well as the future of health care.

PMID- 8294648
TI  - The importance of conduct problems and depressive symptoms in predicting
      adolescent substance use.
AB  - The current study assessed the relative importance of conduct problems and
      depressive symptoms, measured at two ages (11 and 15), for predicting substance
      use at age 15 in an unselected birth cohort of New Zealand adolescents. Among
      males, when the relative predictive utility of both conduct problems and
      depressive symptoms was assessed, only pre-adolescent depressive symptoms were
      found to predict multiple drug use 4 years later. No predictive relation was
      found between early symptomatology and later substance use among females. The
      strongest association between predictors and substance use emerged between age 15
      multiple drug use and concurrent conduct problems for both males and females.
      Finally, both conduct problems and depressive symptoms at age 15 were also found
      to be associated with concurrent "self-medication" among females.

PMID- 8294649
TI  - The criterion-related validity of the Childhood Autism Rating Scale and the
      Autism Behavior Checklist.
AB  - The present study sought to examine the relationship between two popular
      instruments for screening autistic children: the Childhood Autism Rating Scale
      (CARS) and the Autism Behavior Checklist (ABC). The sample included 77
      individuals. The records of 48 subjects contained firm diagnoses of autism, while
      the suggestion of autism was found in the remaining records. Correlations between
      the two scales ranged from -.16 to .73 (median = .39). The validity coefficient
      between the two total scores was .67. Using cutoff scores recommended by the
      authors, an analysis of the sensitivity of the two instruments was conducted. The
      CARS correctly identified 98% of the autistic subjects; it identified 69% of the
      possibly autistic as autistic. The ABC correctly identified 88% of the autistic
      subjects, while it identified 48% of those subjects considered possibly autistic
      as autistic. A phi coefficient was computed to estimate the degree of
      relationship between the nominal classifications produced by the two instruments.
      A moderate relationship was found (r phi = .54). Implications of the results are
      discussed.

PMID- 8294650
TI  - Developmental theories of parental contributors to antisocial behavior.
AB  - In view of the increased interest in a developmental approach to psychopathology,
      and mounting evidence of the importance of parent-child interactions in the
      etiology of early antisocial behavior, the following questions were posed for
      this review. What theories of parent-child relationships and family management
      techniques are available? How developmental are they, how specific and
      transactional are they relative to parent and child behaviors involved? And how
      well do they cover the period in which antisocial behavior develops? Six theories
      have some developmental features but the attachment theories (by L. A. Sroufe, B.
      Egeland, and M. T. Greenberg) and two social learning theories (by G. R.
      Patterson and J. Martin) are most clearly developmental. They postulate
      reciprocal interactions of parent and child, and transformations in the form of
      normative changes in the child or changes in family processes. The social
      learning theories of Patterson and Martin are most specific, microanalytic in
      fact, as to the interaction processes involved, and the attachment theories at
      least specify kinds of behavior involved and also do not rely on traits or types
      of influence as their units of analysis. Conceptualization is most weak and
      overly general between late infancy and the preschool years. This gap makes it
      difficult to link attachment and social learning theories, both of which have
      driven a large number of studies. A bridging theory is offered to link the two
      sets of theories in the critical period involved.

PMID- 8294651
TI  - Teachers' ratings of disruptive behaviors: the influence of halo effects.
AB  - This study evaluated the accuracy of teachers' ratings and examined whether these
      ratings are influenced by halo effects. One hundred thirty-nine elementary school
      teachers viewed videotapes of what they believed were children in regular fourth
      grade classrooms. In fact, the children were actors who followed prepared scripts
      that depicted a child engaging in behaviors characteristic of an attention
      deficit hyperactivity disorder (ADHD), an oppositional defiant disorder or a
      normal youngster. The findings provide support for a bias that was unidirectional
      in nature. Specifically, teachers rated hyperactive behaviors accurately when the
      child behaved like an ADHD youngster. However, ratings of hyperactivity and of
      ADHD symptomatic behaviors were spuriously inflated when behaviors associated
      with oppositional defiant disorder occurred. In contrast, teachers rated
      oppositional and conduct problem behaviors accurately, regardless of the presence
      of hyperactive behaviors. The implications of these findings regarding diagnostic
      practices and rating scale formats are discussed.

PMID- 8294652
TI  - Perceptions of methylphenidate effects on hyperactive children's peer
      interactions.
AB  - The behavioral constructs that emerge from observers' open-ended impressions of
      methylphenidate effects on the social behaviors of hyperactive children were
      examined. Ninety-six undergraduates observed videotapes of two different
      hyperactive "target" boys, each playing an interaction game with three peers. One
      target was taking methylphenidate and the other was taking placebo. The valence
      and content of observers' social perceptions were analyzed. Overall, more
      negative than positive behaviors were detected, a pattern more pronounced for the
      placebo than for the medication condition. Interestingly, placebo targets
      received negative evaluations for poorly controlled behaviors such as
      noncompliance, aggression, and disruption, but medicated targets received
      negative evaluations for social inhibition--passive and submissive behaviors. In
      contrast, the boys' medication state did not consistently influence observers'
      perceptions of positive social behaviors. Discussion focused on the extent and
      consequences of medication-related increases in social disengagement and on the
      ultimate impact of stimulant treatment on hyperactive children's social worlds.

PMID- 8294654
TI  - If not us, then who?

PMID- 8294653
TI  - Parent training for attention-deficit hyperactivity disorder: its impact on
      parent functioning.
AB  - This study examined changes in parent functioning resulting from parental
      participation in a behavioral parent training (PT) program specifically designed
      for school-aged children with attention-deficit hyperactivity disorder (ADHD).
      Relative to wait list controls, subjects who completed the nine-session PT
      program showed significant posttreatment gains in both child and parent
      functioning, which were maintained 2 months after treatment. In particular, there
      were PT-induced reductions in parenting stress and increases in parenting self
      esteem, which accompanied parent-reported improvements in the overall severity of
      their child's ADHD symptoms. In addition to their statistical importance, these
      findings are discussed in terms of their clinical significance, utilizing methods
      developed by Jacobson and Truax (1991).

PMID- 8294655
TI  - Choosing intracoronal restorative materials. Council on Dental Materials,
      Instruments and Equipment.

PMID- 8294657
TI  - List of recognized continuing education providers.

PMID- 8294656
TI  - Detecting, evaluating and treating hypertension.

PMID- 8294658
TI  - Communicable hysteria?

PMID- 8294659
TI  - Coming clean about fees.

PMID- 8294660
TI  - The new Minnesota Health Care Plan.

PMID- 8294661
TI  - Dental dummies.

PMID- 8294662
TI  - Medicare payments rise 13 percent.

PMID- 8294663
TI  - MDR-TB. Another challenge from the microbial world.
AB  - Beginning in 1985, the long decline in TB cases was dramatically reversed; from
      1985 through 1992 reported cases increased 20.1 percent nationally. Two
      characteristics of this resurgent epidemic are unique: its prevalence among
      immunocompromised HIV-infected people and the emergence of multidrug-resistant
      TB. Current epidemiological trends, demographics and treatment approaches are
      discussed, as well as the implications MDR-TB holds for dentistry.

PMID- 8294665
TI  - Changing restorative traditions: the use of bases and liners.

PMID- 8294664
TI  - Current status of diagnostic procedures for temporomandibular disorders.
AB  - Temporomandibular disorders encompass a group of musculoskeletal conditions that
      involve the joints, the masticatory musculature, or both. In any given patient,
      there may be several overlapping TM disorders, an orofacial pain condition
      mimicking a TM disorder or a concomitant TMD and non-TM disorder. The
      differential diagnosis becomes extremely important.

PMID- 8294666
TI  - Addressing family violence among dental patients: assessment and intervention.
AB  - Health care professionals increasingly encounter family violence victims, but
      often do not recognize the signs of abuse. A mailed survey and personal
      interviews with dental health care workers reveal an uncertainty about
      intervening when abuse is suspected. The authors examine DHCWs exposure to family
      violence among their patients, educational history and thoughts about
      intervention.

PMID- 8294667
TI  - Treating oral sarcoidosis.
AB  - Oral sarcoidosis is rare and can be confused with various other lesions. Two case
      reports of sarcoidosis involving the lips are presented along with a discussion
      of sarcoidosis and treatment options.

PMID- 8294668
TI  - Using rubber dams to boost quality, quantity of restorative services.
AB  - Rubber dam use for restorative dentistry is far too low. If practitioners
      realized rubber dam's advantages and increased treatment quality, its use would
      be irresistible. Few other dental procedures offer both an increase in operating
      speed and treatment quality. To save the most time, competent auxiliary staff
      should be taught to place rubber dams before the clinical procedure begins.
      (Additional information on rubber dam placement by auxiliary staff is available
      from Dr. Christensen.)

PMID- 8294669
TI  - Managing the perceptions of patient wait time.
AB  - Patients' perception of waiting time in the dental office can greatly affect
      their satisfaction of service. Traditional approaches to managing patient
      perceptions of wait time are discussed, and some new strategies are explored.

PMID- 8294670
TI  - Pharmaceuticals and periodontal diseases.

PMID- 8294671
TI  - Dentists as physicians of the mouth.

PMID- 8294672
TI  - Advances in salivary and soft tissue management.

PMID- 8294673
TI  - The medical management of dental caries.

PMID- 8294674
TI  - How pharmaceuticals are developed.

PMID- 8294675
TI  - Insurance issues and new treatments.

PMID- 8294676
TI  - Trends in the health sciences.

PMID- 8294677
TI  - Oral pharmaceuticals and adult dental patients.

PMID- 8294678
TI  - Circadian pattern of arrhythmic death in patients receiving encainide, flecainide
      or moricizine in the Cardiac Arrhythmia Suppression Trial (CAST).
AB  - OBJECTIVES: The purpose of this study was to assess the effect of antiarrhythmic
      drugs on the timing of arrhythmic death. BACKGROUND: Sudden cardiac death remains
      a problem of epidemic proportions. Delineating its pathophysiology is an
      important step in devising preventive measures. Previous studies have shown a
      circadian pattern of onset of sudden cardiac death. The effect of antiarrhythmic
      drugs on this pattern has not been systematically studied. METHODS: The Cardiac
      Arrhythmia Suppression Trial (CAST) was a multicenter double-blind, placebo
      controlled study designed to determine whether suppression of ventricular ectopic
      activity by means of antiarrhythmic drugs (encainide, flecainide or moricizine)
      after acute myocardial infarction would reduce the incidence of arrhythmic death.
      RESULTS: The trial was terminated prematurely because of an unexpectedly high
      mortality rate in the active treatment group. The onset of arrhythmic death in
      this group (in patients not receiving beta-adrenergic blocking agents) displayed
      a bimodal variation, with significant peaks in midmorning and late
      afternoon/early evening. More than half of the symptomatic events were
      accompanied by anginalike symptoms. Approximately 30% of all events occurred
      within 2 h of awakening. CONCLUSIONS: Our data suggest the possibility of a
      complex interaction among antiarrhythmic drugs, sympathetic nervous system
      activation and acute myocardial ischemia. Planning of future antiarrhythmic drug
      trials will need to take this information into account.

PMID- 8294679
TI  - Transesophageal echocardiography before and during direct current cardioversion
      of atrial fibrillation: evidence for "atrial stunning" as a mechanism of
      thromboembolic complications.
AB  - OBJECTIVES: The purpose of this study was to evaluate the usefulness of
      transesophageal echocardiography before electrical cardioversion in patients with
      atrial fibrillation and to determine the mechanism of thromboembolism after
      cardioversion. BACKGROUND: Thromboembolic complications after electrical
      cardioversion of atrial fibrillation have been attributed to the dislodgment of
      preexistent left atrial thrombus during the resumption of atrial contraction.
      Transesophageal echocardiography has been proposed as a method of screening
      patients for left atrial thrombus before cardioversion. METHODS: Seventy
      transesophageal echocardiographic studies were performed in 66 patients,
      predominantly with nonvalvular atrial fibrillation, before direct current
      cardioversion. In addition, transesophageal echocardiography was performed during
      the cardioversion procedure in 15 patients and immediately after in 1 patient.
      RESULTS: Left atrial thrombus was detected in one patient (1.4%), and
      cardioversion was cancelled. Thromboembolic complications occurred in 4 patients,
      none of whom had evidence of left atrial thrombus before cardioversion. Within 10
      s of successful cardioversion, left atrial spontaneous echo contrast appeared in
      five patients, increased in one patient and was unchanged in nine patients.
      Patients with new or increased spontaneous echo contrast had more impaired atrial
      contraction and slower initial heart rates after cardioversion than those
      without. Left ventricular contraction was also impaired transiently by
      cardioversion. CONCLUSIONS: Transesophageal echocardiographic detection of left
      atrial thrombus before direct current cardioversion is important but infrequent
      in patients with predominantly nonvalvular atrial fibrillation. The occurrence of
      thromboembolic complications in the absence of demonstrable left atrial thrombus
      and the new development of spontaneous echo contrast in association with the
      transient atrial dysfunction ("stunning") caused by cardioversion suggest that
      cardioversion may promote new thrombus formation, in which case all patients
      should receive full anticoagulant therapy at the time of cardioversion.

PMID- 8294680
TI  - Combination biphasic waveform plus sequential pulse defibrillation improves
      defibrillation efficacy of a nonthoracotomy lead system.
AB  - OBJECTIVES: We hypothesized that combining biphasic waveform and sequential pulse
      defibrillation techniques would lower the defibrillation threshold of a
      nonthoracotomy lead system in humans below that obtained with biphasic or
      sequential pulse defibrillation alone. BACKGROUND: Previous studies have shown
      that sequential pulse monophasic shocks and biphasic waveform shocks are more
      effective than single monophasic shocks for ventricular defibrillation. METHODS:
      Thirteen patients aged 48 to 71 years undergoing nonthoracotomy defibrillation
      lead testing participated in the study. Transvenous electrodes were positioned in
      the right ventricular apex, superior vena cava and coronary sinus. A cutaneous
      patch electrode was placed on the left chest wall. All electrodes were connected
      to an external defibrillator. In random order, defibrillation threshold
      measurements were made for biphasic defibrillation alone, sequential
      defibrillation alone and combined biphasic plus sequential defibrillation.
      RESULTS: The mean defibrillation threshold-delivered energy was 18.0 +/- 11.9 J
      for biphasic defibrillation and 16.3 +/- 9.0 J for sequential defibrillation.
      Biphasic plus sequential defibrillation significantly reduced the threshold
      energy to 10.2 +/- 5.3 J (p < 0.001). Threshold peak voltage and current values
      showed corresponding reductions. The combined waveform resulted in a greater
      reduction in defibrillation threshold in patients with threshold energies > 18 J
      versus those with threshold values < or = 18 J for sequential (p = 0.001) or
      biphasic (p < 0.01) waveform alone. The nonthoracotomy lead implantation rate was
      improved from 62% with each of the single techniques (biphasic waveform or
      sequential pulse defibrillation) to 85% with the combined waveform. CONCLUSIONS:
      Adding biphasic waveform to sequential pulse defibrillation significantly reduced
      the defibrillation threshold compared with either technique alone, and
      nonthoracotomy lead system implantation can be enhanced by this combined
      technique.

PMID- 8294681
TI  - Percutaneous excimer laser coronary angioplasty: results in the first consecutive
      3,000 patients. The ELCA Investigators.
AB  - OBJECTIVES: We report the comprehensive results of the first consecutive 3,000
      patients treated in an excimer laser coronary angioplasty registry. BACKGROUND:
      Excimer laser coronary angioplasty involves the use of a pulsed, 308-nm
      ultraviolet laser transmitted by optical fibers to reduce coronary stenoses.
      Preliminary reports have described safety and efficacy profiles in small numbers
      of patients. METHODS: Patients were enrolled in a prospective, nonrandomized
      manner. The catheters used were 1.3, 1.6, 2.0, 2.2 and 2.4 mm in diameter, at
      energy densities up to 70 mJ/mm2. Procedures were performed by standard
      angioplasty technique with conventional guide catheters. RESULTS: Seventy-five
      percent of patients were male, 68% were in Canadian Cardiovascular Society
      functional class III or IV and the cohort included 3,592 lesions. Procedural
      success (final stenosis < or = 50% without in-hospital Q wave myocardial
      infarction, coronary artery bypass surgery or death) was 90% and did not differ
      between the first 2,000 and the last 1,000 patients treated. There was no
      significant difference in success or complication rates with respect to lesion
      length, nor were there differences between selected complex and simple lesions.
      Complications included in-hospital bypass surgery (3.8%), Q wave myocardial
      infarction (2.1%) and death (0.5%). Coronary artery perforation occurred in 1.2%
      of patients (1% of lesions) but significantly decreased to 0.4% in the last 1,000
      patients (0.3% of lesions). Angiographic dissection occurred in 13% of lesions,
      transient occlusion in 3.4% and sustained occlusion in 3.1%. Comprehensive lesion
      morphologic data collected in the latter portion of the study showed the
      procedure predominantly limited to American College of Cardiology-American Heart
      Association type B2 and C lesions, with no significant difference in short-term
      outcome between groups. CONCLUSIONS: Excimer laser angioplasty can be safely and
      effectively applied, even in a variety of complex lesions not well suited for
      percutaneous transluminal coronary angioplasty. These types may include aorto
      ostial, long lesions, total occlusions crossable with a wire, diffuse disease and
      vein grafts. Most recent data show a trend for the selection of predominantly
      complex lesions and a reduction in the incidence of perforation. This procedure
      may broaden the therapeutic window for the interventional treatment of selected
      complex coronary artery disease.

PMID- 8294682
TI  - Coronary perforation after excimer laser coronary angioplasty: the Excimer Laser
      Coronary Angioplasty Registry experience.
AB  - OBJECTIVES: This study assessed the frequency of perforation with excimer
      coronary angioplasty. BACKGROUND: Coronary artery perforation after conventional
      percutaneous transluminal coronary angioplasty is extremely rare. Because laser
      coronary angioplasty involves actual tissue ablation, it has an increased
      potential for perforation. METHODS: All patients in the Excimer Laser Coronary
      Angioplasty Registry were included in this prospective study. Those who had a
      perforation related to the procedure were compared with those who did not have
      this complication. RESULTS: Of 2,759 consecutive patients in the Excimer Laser
      Coronary Angioplasty Registry, 36 (1.3%) had perforation. In these patients, the
      left anterior descending coronary artery was the most frequently treated vessel
      (53%). There were no differences in fiber sizes between patients with and those
      without perforation. Among the patients with perforation, 36.1% required coronary
      artery bypass surgery, 16.7% experienced an infarction and 5.6% had a fatal
      outcome. Among the patients without perforation, the rates were 3.1%, 3.8% and
      0.6%, respectively. However, 41.7% of the patients with documented coronary
      artery perforation did not need coronary artery bypass surgery or experience
      myocardial infarction or death. No angiographic characteristics distinguished
      lesions with from those without perforation. The frequency of coronary artery
      perforation declined over time with increasing operator experience, from 1.6% in
      the first 1,888 patients to only 0.4% in the last 1,000 patients (p = 0.002).
      CONCLUSIONS: With increasing operator experience, the rate of perforation with
      excimer laser coronary angioplasty has decreased. When perforation occurs,
      subsequent event rates increase.

PMID- 8294683
TI  - Radiofrequency thermal balloon coronary angioplasty: a new device for successful
      percutaneous transluminal coronary angioplasty.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effects of thermal
      balloon percutaneous transluminal coronary angioplasty using radiofrequency
      energy in the treatment of patients with failed coronary angioplasty and complex
      lesions. In addition, we evaluated restenosis after radiofrequency thermal
      balloon applications. BACKGROUND: The efficacy of coronary angioplasty is limited
      by the relatively low success rate in complex lesions and the high frequency of
      restenosis. Few reports have studied the combined effects of pressure and laser
      thermal energy. This study describes a new device for coronary angioplasty using
      radiofrequency thermal energy. METHODS: Thirty-two patients with failed
      conventional coronary angioplasty or complex lesions were treated with
      radiofrequency thermal balloon coronary angioplasty. Radiofrequency energy was
      delivered up to 11 times in exposures ranging from 30 to 60 s in duration. This
      combined effect allowed the vascular wall to be heated to temperatures ranging
      from 60 to 70 degrees C. Follow-up coronary angiography was performed, on
      average, 6 months after the procedure. RESULTS: Successful radiofrequency
      coronary angioplasty was achieved in 28 (82%) of 34 lesions. There was one abrupt
      coronary artery occlusion (3%) and no death, perforation or dissection.
      Angiographic restenosis occurred in 14 (56%) of 25 lesions. CONCLUSIONS: In
      patients with failed coronary angioplasty and difficult complex lesions,
      radiofrequency coronary angioplasty could potentially improve angioplasty success
      rates and may have important implications for bailout cases with abrupt
      occlusion. However, restenosis remains a significant problem.

PMID- 8294684
TI  - Neointimal coverage of stents in human coronary arteries observed by angioscopy.
AB  - OBJECTIVES: The aim of this study was to reveal the time course of the neointimal
      coverage of stents placed in the human coronary arteries. BACKGROUND: In deciding
      the protocol of anticoagulant and antiplatelet therapy for patients who undergo
      stent implantation, the condition of the neointimal coverage of stents should be
      taken into consideration. However, the time course of the neointimal coverage of
      stents has not been elucidated in human coronary arteries. METHODS: Serial
      angioscopic observations were performed immediately after stenting, at 8 to 45
      days (short-term follow-up) and at 65 to 142 days (long-term follow-up) in
      patients who underwent implantation of the Wiktor coronary stent in the
      restenotic lesion or in the lesion of acute or threatened closure after balloon
      angioplasty. RESULTS: Angioscopic observations were successfully performed in 14
      cases immediately after stenting, in 11 cases at short-term follow-up and in 13
      cases at long-term follow-up. Immediately after stenting and even at 8 to 18 days
      after stenting, the stent was not covered by the neointimal layer in any case.
      However, at 65 to 142 days after stenting, the stent was covered by the
      neointimal layer in all cases. Angioscopically, three types of neointimal layer
      were recognized: a white layer with a cottonlike surface in three cases, a white
      layer with a smooth surface in eight cases and a transparent layer with a smooth
      surface in two cases. CONCLUSIONS: Although some experimental results in animals
      have shown completion of neointimal coverage of stents in a few weeks, in this
      serial angioscopic follow-up study, the completion of neointimal coverage of
      stents in human coronary arteries required approximately 3 months.

PMID- 8294685
TI  - Does the use of new intracoronary interventional devices prolong radiation
      exposure in the cardiac catheterization laboratory?
AB  - OBJECTIVES: The aim of this study was to compare the duration of radiation
      exposure associated with new percutaneous coronary interventional devices with
      that associated with conventional balloon angioplasty. BACKGROUND: Radiation
      exposure levels have been documented to be higher with coronary balloon
      angioplasty than with routine diagnostic coronary angiography. However, the
      effect of new interventional devices on radiation exposure has not been studied.
      METHODS: Fluoroscopic and cineangiographic data from the Mayo Clinic cardiac
      catheterization laboratory data base of patients having single-segment coronary
      intervention during a recent 46-month period were retrospectively analyzed. Of
      897 patients studied, 646 underwent balloon angioplasty, 138 directional coronary
      atherectomy (42 with adjunctive balloon angioplasty), 76 excimer laser
      angioplasty (50 with adjunctive balloon angioplasty) and 37 placement of an
      intracoronary stent (16 emergencies). RESULTS: Duration of fluoroscopy during
      balloon angioplasty was 24 +/- 18 min, which was longer than with directional
      atherectomy (18 +/- 8 min; p = 0.001). Fluoroscopy time was 25 +/- 17 min with
      laser angioplasty and 29 +/- 15 min with elective stent placement (neither time
      was significantly different from that with balloon angioplasty). When atherectomy
      or laser angioplasty was performed with adjunctive balloon angioplasty or if
      emergency intracoronary stent placement was performed, the duration of
      fluoroscopy was significantly prolonged compared with balloon angioplasty alone.
      CONCLUSIONS: Fluoroscopy duration is not prolonged with the use of new
      interventional coronary devices compared with conventional angioplasty unless
      adjunctive balloon angioplasty is used or emergency stent placement is required.

PMID- 8294686
TI  - Intravascular ultrasound detection of atherosclerosis at the site of focal
      vasospasm in angiographically normal or minimally narrowed coronary segments.
AB  - OBJECTIVES: The purpose of this study was to use intravascular ultrasound imaging
      to examine the presence of occult atherosclerosis at the site of focal vasospasm
      in angiographically normal or minimally narrowed segments, testing the role of
      atherosclerosis in the development of vasospasm. BACKGROUND: Previous clinical
      and experimental studies have suggested that early atherosclerosis is present at
      the site of focal vasospasm. However, no clinical data exist demonstrating occult
      disease at the site of vasospasm at angiographically insignificant stenoses.
      METHODS: Twenty-two patients with chest pain at rest or during exertion, or both,
      were studied. Vasospasm was provoked by intracoronary administration of
      ergonovine maleate (0.01 to 0.04 mg). After relief of vasospasm by nitroglycerin
      administration, intravascular ultrasound imaging was performed with a 32- or 64
      element, 20-MHz, synthetic aperture array ultrasound device. RESULTS: Focal
      vasospasm (arterial diameter reduction > or = 90%) with ST-T segment elevation
      was provoked in 15 patients: in the left anterior descending coronary artery in 8
      patients and in the right coronary artery in 7. The remaining seven patients
      (control group) showed diffuse narrowing, averaging 22 +/- 12% (mean +/- SD) in
      diameter from the baseline angiograms after ergonovine administration.
      Atherosclerosis, defined as a significantly thickened intimal leading edge (0.42
      +/- 0.07 mm) associated with an increased sonolucent zone (0.57 +/- 0.30 mm), was
      detected by ultrasound at all 15 sites with focal vasospasm, although these sites
      were normal or minimally narrowed by angiography. In contrast, seven segments
      from the control group exhibited a thin intimal leading edge (0.14 +/- 0.04 mm, p
      < 0.01) and sonolucent zone (0.10 +/- 0.07 mm, p < 0.01), indicating the absence
      of localized atherosclerotic lesions. CONCLUSIONS: These results indicate that
      atherosclerosis is present at the site of focal vasospasm, even in the absence of
      angiographically significant coronary disease. We suggest that the existence of
      such atherosclerotic lesions is related to the occurrence of focal vasospasm in
      the clinical settings.

PMID- 8294687
TI  - Prognostic significance of peak exercise capacity in patients with coronary
      artery disease.
AB  - OBJECTIVES: The aim of this study was to investigate the prognostic significance
      of peak oxygen uptake in patients with coronary artery disease who had an
      exercise test that could be sustained to exhaustion without limiting symptoms.
      BACKGROUND: Many studies have reported an inverse association between the level
      of exercise reached during a stress test and mortality or cardiovascular
      morbidity. These studies have used submaximal or symptom-limited exercise testing
      in patients with a recent myocardial infarction. METHODS: Peak oxygen uptake was
      measured in male patients > or = 4 weeks after myocardial infarction (312
      patients) or coronary artery surgery (215 patients) by use of a graded
      uninterrupted exercise test performed to exhaustion. Apart from peak oxygen
      uptake, several risk factors for cardiovascular disease, patient and exercise
      characteristics and drug treatment were considered in the Cox proportional
      hazards model. RESULTS: During the total follow-up period of 3,213 patient-years,
      53 patients died. Of these 53 patients, 33 died of cardiovascular causes. All
      cause and cardiovascular mortality decreased with increasing peak oxygen uptake,
      even after adjustment for significant covariates. The relative hazard rates of
      0.43 and 0.29 indicate that a hypothetic increase in peak oxygen uptake by 1
      liter/min could be associated with decreases in all-cause and cardiovascular
      mortality of 57% and 71%, respectively. CONCLUSIONS: Exercise capacity is an
      independent predictor for subsequent all-cause and cardiovascular mortality in
      patients able to perform an exercise test until exhaustion.

PMID- 8294688
TI  - Hyperinsulinemia, coronary artery disease and syndrome X.
AB  - OBJECTIVES: This study was conducted to compare the insulin responses to an oral
      glucose load in healthy volunteers and patients with syndrome X and patients with
      coronary artery disease. BACKGROUND: An abnormal coronary flow reserve has been
      reported in syndrome X by several investigators. However, its cause is not known.
      Recently, it has been suggested that elevated insulin levels in syndrome X may
      contribute to microvascular dysfunction. METHODS: Insulin responses to an oral
      glucose load (75 g) were compared in 17 patients with coronary artery disease, 17
      patients with chest pain, positive exercise test findings, normal coronary
      arteries and impaired coronary flow reserve (syndrome X) and 17 healthy
      volunteers (control subjects). All were matched for age, gender and body weight.
      Patients with overt diabetes mellitus or hypertension were excluded. Venous blood
      samples were taken during fasting and at 30, 60, 90 and 120 min after the glucose
      load. Samples were analyzed for glucose, immunoreactive insulin and C peptides.
      RESULTS: There was no significant difference in the glucose levels at all
      sampling points among the three groups. The C peptide and immunoreactive insulin
      levels were significantly higher than values in the control group at 60, 90 and
      120 min in the groups with syndrome X and coronary artery disease. The peak
      responses and the areas under the curve were also significantly greater in the
      latter two groups. There was no significant difference at all sampling points
      between the group with syndrome X and the group with coronary artery disease.
      CONCLUSION: Patients with syndrome X have stimulated hyperinsulinemia, which may
      contribute to the pathophysiology of syndrome X.

PMID- 8294689
TI  - Truly silent ischemia and the relationship of chest pain and ST segment changes
      to the amount of ischemic myocardium: evaluation by supine bicycle stress
      echocardiography.
AB  - OBJECTIVES: The objectives of this study were 1) to determine the relationship
      between the amount of exercise-induced ischemic myocardium and the presence or
      absence of chest pain and ST segment depression, and 2) to define the incidence
      and characteristics of "truly silent ischemia," that is, ischemia that is not
      manifested by symptoms or electrocardiographic (ECG) findings. BACKGROUND: There
      are no prior data relating ischemia to chest pain and ST depression. Thallium-201
      imaging studies have evaluated perfusion but not ischemia. In contrast, supine
      bicycle stress echocardiography demonstrates exercise-induced ischemic
      dysfunction. METHODS: Supine bicycle stress echocardiography and arteriography
      were performed in 130 patients and the severity and geographic extent of ischemic
      myocardium were compared in three groups. On exercise, Group I patients had both
      chest pain and ST segment depression (symptomatic ischemia), Group II patients ST
      depression without chest pain (asymptomatic ischemia) and Group III patients had
      neither chest pain nor ST depression (truly silent ischemia). RESULTS: There were
      no differences among groups in arteriographic characteristics. The incidence of
      "truly silent ischemia" was 43%. The number of abnormally contracting ischemic
      segments, average score per segment and sum of scores were virtually identical in
      Groups I and II and significantly greater than in Group III for the patients (p <
      0.01 to < 0.0001), for the vessels as a group (p < 0.01 to < 0.0001) and for the
      left anterior descending (p < 0.01 to < 0.0001) and right (p < 0.05) coronary
      arteries. By multivariate analysis, positive findings on the stress ECG was the
      single most significant variable in relation to the amount of ischemia (p <
      0.001); exercise chest pain had no significant relationship. CONCLUSIONS:
      Exercise-induced ST segment depression is the single most significant variable in
      relation to the amount of ischemic myocardium; exercise-induced chest pain is not
      related to the amount of ischemia. Patients with "truly silent ischemia"
      constitute almost 50% of patients with coronary artery disease and have less
      ischemia than do patients with ECG indications of ischemia, with or without chest
      pain.

PMID- 8294690
TI  - Insulin resistance, lipoproteins, body fat and hemostasis in nonobese men with
      angina and a normal or abnormal coronary angiogram.
AB  - OBJECTIVES: The aim of this study was to compare metabolic risk factors in men
      with anginal chest pain and a normal or abnormal coronary angiogram with those in
      healthy men. BACKGROUND: Risk factors for coronary heart disease, including
      lipoprotein abnormalities, hypertension and adiposity, may be metabolically
      interlinked, with insulin resistance and hyperinsulinemia being pivotal to these
      disturbances. METHODS: Glucose and insulin metabolism, lipids and lipoproteins,
      hemostasis, blood pressure and body fat distribution were measured in 77 nonobese
      middle-aged men who had anginal chest pain (39 with an abnormal coronary
      angiogram and 38 with no detectable angiographic abnormality) and were compared
      with those of 40 healthy men of similar age and body mass index. RESULTS:
      Patients with chest pain had higher insulin responses to an intravenous glucose
      challenge, lower insulin sensitivity, lower high density lipoprotein (HDL) and
      subfraction 2 cholesterol, lower apolipoprotein AI, higher triglycerides, greater
      android fat and higher systolic blood pressure at rest compared with levels in
      healthy control subjects (p < 0.05). Those with an abnormal coronary angiogram
      had lower tissue plasminogen activator levels, higher plasminogen activator
      inhibitor 1 levels and more android fat than did those with a normal angiogram (p
      < 0.05). Insulin sensitivity correlated positively with HDL (p < 0.05) and
      subfraction 2 (p < 0.001) cholesterol and negatively with triglycerides (p <
      0.01), android fat proportion (p < 0.01) and systolic blood pressure (p < 0.05),
      whereas insulin response showed converse correlations. CONCLUSIONS: These
      findings provide new evidence of the central role of insulin resistance and
      hyperinsulinemia in the development of risk factors associated with coronary
      heart disease.

PMID- 8294691
TI  - Safety profile of adenosine stress perfusion imaging: results from the Adenoscan
      Multicenter Trial Registry.
AB  - OBJECTIVES: The purpose of this study was to determine the safety of adenosine
      infusion at 140 micrograms/kg per min in conjunction with radionuclide imaging in
      9,256 consecutive patients. BACKGROUND: Adenosine produces maximal myocardial
      hyperemia directly with a rapid onset of action. In addition, when used in
      conjunction with radionuclide perfusion imaging, it has proven efficacy for the
      diagnosis of coronary artery disease in patients unable to exercise. Because the
      ultrashort half-life (< 10s) allows dose titration and rapid reversal of side
      effects, it may be safer than other available pharmacologic agents. METHODS:
      Patients were prospectively entered at 21 clinical sites. Information on safety
      and adverse events during and immediately after adenosine infusion was maintained
      in the Adenoscan Multicenter Trial Registry. RESULTS: The infusion protocol was
      completed in 80% of patients, required dose reduction in 13% and was terminated
      early in 7%. Interpretable imaging studies were obtained in 98.7% of patients,
      and 0.8% of patients received aminophylline. Minor and well tolerated side
      effects were reported in 81.1% of patients. There were no deaths, one myocardial
      infarction, seven episodes of severe bronchospasm and one episode of pulmonary
      edema. Transient atrioventricular (AV) node block occurred in 706 patients (first
      degree in 256, second-degree in 378 and third-degree in 72) and resolved
      spontaneously in most patients (n = 508) without alteration in the adenosine
      infusion. There were no sustained episodes of AV block. Patients > 70 years of
      age had an increased risk of developing AV block (age < 70, 7.05% vs. > or = 70,
      9.44%, p = 0.001, relative risk 1.37). CONCLUSIONS: Adenosine infusion is safe.
      Vasodilator and negative dromotropic side effects are generally well tolerated.
      Serious side effects are relatively rare, and they reverse with termination of
      adenosine infusion. Interpretable radionuclide studies were obtained in 98.7% of
      patients and aminophylline reversal was seldom required.

PMID- 8294692
TI  - Dipyridamole and adenosine vasodilator stress for myocardial imaging: vive la
      difference!

PMID- 8294693
TI  - Quality of life among 5,025 patients with left ventricular dysfunction randomized
      between placebo and enalapril: the Studies of Left Ventricular Dysfunction. The
      SOLVD Investigators.
AB  - OBJECTIVES: This study was performed to assess the quality of life of patients
      with left ventricular dysfunction for up to 2 years after randomization to
      enalapril or placebo. BACKGROUND: Previous reports have documented that survival
      of patients with congestive heart failure can be extended by the angiotensin
      converting enzyme inhibitor enalapril. However, it is unknown whether enalapril
      has a long-term favorable impact on the quality of life in patients with heart
      failure. METHODS: A brief quality of life questionnaire assessing the quality of
      life was administered at baseline and at 6 weeks, 1 year and 2 years of follow-up
      to patients randomized to placebo or enalapril in the Studies of Left Ventricular
      Dysfunction (SOLVD). Participants had an ejection fraction < or = 0.35, no other
      serious illnesses and either symptomatic heart failure (treatment trial, n =
      2,465) or asymptomatic left ventricular dysfunction (prevention trial, n =
      2,560). RESULTS: Among the 14 scales of quality of life, better scores at one or
      more follow-up intervals were noted in 6 scales in the treatment trial and in 1
      scale in the prevention trial among patients assigned to enalapril. Consistent
      superiority with enalapril at two consecutive follow-up intervals was noted in
      the treatment trial for social functioning and dyspnea but for no scale in the
      prevention trial. However, an average of 40% of quality of life responses were
      missing at 2 years of follow-up because of death or failure to complete the
      questionnaire. In the treatment trial, survivors with more severe heart failure
      were less likely to complete the questionnaire. CONCLUSIONS: Modest benefits in
      quality of life for > or = 1 year occurred when patients with left ventricular
      dysfunction and symptomatic heart failure were treated with enalapril. No
      apparent beneficial or adverse effect on quality of life was observed with
      enalapril in asymptomatic patients with left ventricular dysfunction.

PMID- 8294694
TI  - Arterial baroreflex regulation of blood pressure in patients with congestive
      heart failure.
AB  - OBJECTIVES: This study was designed to determine whether arterial baroreflex
      control of blood pressure is altered in patients with congestive heart failure.
      BACKGROUND: Arterial baroreceptor reflexes normally contribute to cardiovascular
      homeostasis by preserving blood pressure during changes in volume and posture.
      METHODS: Arterial baroreceptor reflex function was studied in 18 patients with
      congestive heart failure and 18 age-matched healthy subjects. The arterial
      baroreceptor-blood pressure reflex was assessed by measuring the blood pressure
      response to perturbations in carotid sinus pressure. Carotid baroreceptors were
      stimulated by applying negative pressure to a custom neck chamber (-10, -20 and 
      30 mm Hg) and were unloaded by applying neck positive pressure (+10, +20 and +30
      mm Hg). RESULTS: Peak carotid baroreceptor-blood pressure reflex sensitivity was
      lower in patients with heart failure than in normal subjects (0.19 +/- 0.02 vs.
      0.30 +/- 0.03 mm Hg/mm Hg, p < 0.05). During neck positive pressure, blood
      pressure increased less in the heart failure group than in the normal group.
      During neck suction, however, the decrease in blood pressure was similar in the
      two groups. CONCLUSIONS: Patients with heart failure are less able than normal
      subjects to increase blood pressure during arterial baroreceptor unloading, but
      they can reduce blood pressure appropriately during baroreceptor stimulation.
      These observations suggest that the resting blood pressure position on the
      arterial baroreceptor stimulus-response curve, the operational point, is closer
      to the baroreceptor threshold in patients with heart failure than in normal
      subjects. As a result, reduced inhibitory signals from arterial baroreceptors
      most likely contribute to a heightened state of sympathetic activity and
      vasoconstriction in patients with congestive heart failure.

PMID- 8294695
TI  - Relation between ventriculoarterial coupling and myocardial energetics in
      patients with idiopathic dilated cardiomyopathy.
AB  - OBJECTIVES: The purpose of this study was to evaluate left ventricular
      contractility, arterial loading conditions and the way their interaction affects
      myocardial energetics. BACKGROUND: Ventriculoarterial coupling, defined as the
      ratio of effective arterial elastance to left ventricular end-systolic elastance,
      is known to reflect the mechanoenergetic performance of the heart. However,
      relations between the coupling and efficiencies of energy transfer from oxygen
      consumption to hydraulic energy have not been fully investigated in failing
      hearts. METHODS: Pressure-volume data were measured in 23 patients with
      idiopathic dilated cardiomyopathy by using a conductance catheter, and myocardial
      oxygen consumption was obtained simultaneously in 16 patients by a double
      thermistor coronary sinus catheter. End-systolic elastance was determined by
      transient inferior cava occlusion. RESULTS: Data are reported as mean value +/-
      SE. Ventriculoarterial coupling at baseline was 3.24 +/- 0.28. It decreased from
      3.12 +/- 0.43 to 1.86 +/- 0.15 (p < 0.05) for the group receiving dobutamine
      infusion and from 3.16 +/- 0.45 to 1.78 +/- 0.22 (p < 0.01) for the group
      receiving the oral phosphodiesterase inhibitor MS-857. The ratio of pressure
      volume area to myocardial oxygen consumption had a positive correlation with
      ventriculoarterial coupling. The ratio of external work to pressure-volume area
      had a hyperbolic correlation with the coupling. The mechanical efficiency defined
      as the ratio of external work to myocardial oxygen consumption remained within a
      narrow range (16.4 +/- 1.2%). CONCLUSIONS: The degree of ventriculoarterial
      coupling is far from optimal and the cardiovascular performance is severely
      depressed mechanically and energetically in patients with idiopathic dilated
      cardiomyopathy. Although inotropic agents improve the coupling, they have a
      minimal effect on mechanical efficiency.

PMID- 8294696
TI  - Antenatal diagnosis of coarctation of the aorta: a multicenter experience.
AB  - OBJECTIVES: The purpose of this study was to test observations that might aid
      prenatal prediction of the presence of coarctation of the aorta in newborn
      infants with and without other forms of heart disease. BACKGROUND: Previous
      reports have suggested that abnormal growth of the aortic arch in utero may be
      identifiable as a marker for the diagnosis of coarctation. METHODS: We reviewed
      the prenatal echocardiograms and postnatal outcome of 20 infants (gestational age
      at initial study 18 to 36 weeks) with coarctation of the aorta established
      postnatally, to identify echocardiographic findings that would most facilitate
      the prenatal diagnosis of coarctation. Associated cardiac lesions included double
      inlet left ventricle anatomy (n = 5), double-outlet right ventricle (n = 4),
      abnormal aortic valve (n = 5), unbalanced atrioventricular canal (n = 3), and
      membranous ventricular septal defect (n = 1). Chromosomal abnormalities included
      XO karyotype (n = 1), trisomy 18 (n = 1), and trisomy 21 (n = 1). RESULTS:
      Hypoplasia determined by measurement of the distal aortic arch was the most
      frequently observed finding among the fetuses with coarctation. In 12 of 15
      fetuses with a well visualized transverse arch at initial prenatal study, the
      diameter of the transverse arch was < or = 3rd percentile for gestational age as
      compared with that in a normal group of fetuses. Ten of 10 fetuses with adequate
      images of the isthmus had isthmus hypoplasia at prenatal study with a diameter <
      or = 3rd percentile for gestational age. On serial study in six of seven,
      including three fetuses with normal distal arch measurements at initial study,
      the distal arch became progressively more hypoplastic for gestational age. In
      three there was no growth of the transverse arch or isthmus on serial study, and
      in three there was reversal of flow from antegrade to retrograde through the
      distal arch. CONCLUSIONS: In our study, quantitative hypoplasia of the isthmus
      and transverse arch was the most consistent observation and therefore the most
      definitive antenatal sign of postnatal coarctation. The potential for progression
      of distal arch hypoplasia necessitates serial study in fetuses with associated
      cardiac and noncardiac lesions.

PMID- 8294697
TI  - Myocardial perfusion, function and exercise tolerance after the arterial switch
      operation.
AB  - OBJECTIVES: This study was conducted to determine the prevalence of myocardial
      perfusion abnormalities at rest and exercise and to assess exercise capacity in
      children after the arterial switch operation. BACKGROUND: There have been
      sporadic reports of myocardial ischemia or sudden death in children after the
      arterial switch operation for transposition of the great arteries, possibly
      related to inadequate coronary perfusion due to kinking or stenosis of the
      translocated coronary arteries. METHODS: Myocardial perfusion at rest and peak
      exercise was assessed using the scintigraphic agent technetium-99m
      methoxyisobutyl isonitrile (sestamibi). Exercise capacity was determined with a
      modified Bruce protocol. Ambulatory electrocardiographic (ECG) Holter monitoring
      was performed. Ventricular function, contractility and wall motion were assessed
      echocardiographically. RESULTS: Twenty-three children (aged 4.2 to 7.9 years)
      underwent evaluation. Abnormalities were found on the rest perfusion scans in 22
      children (95.6%). The left ventricular myocardium was divided into 13 segments
      for analysis. Of 299 rest segments, 225 (75.3%) were normal, 11 (3.7%) showed
      mild defects, 45 (15%) moderate defects and 18 (6%) severe defects at rest. At
      peak exercise, 237 segments (79.3%) were normal, 24 (8%) showed mild defects, 33
      (11%) moderate defects and 5 (1.7%) severe defects. Compared with rest studies,
      myocardial perfusion grade at exercise was unchanged in 246 segments (82.3%),
      improved in 42 (14%) and worsened in 11 (3.7%). All patients had normal exercise
      tolerance without symptoms or ischemic ECG changes. No ventricular tachycardia
      was seen on Holter monitoring. All patients had a shortening fraction > or = 27%.
      Left ventricular contractility was normal in 12 children in whom it was assessed.
      Regional wall motion was normal in 17 children with adequate echocardiographic
      images for this analysis. CONCLUSIONS: Myocardial perfusion scan abnormalities
      assessed by technetium-99m sestamibi are common after an arterial switch
      operation. These abnormalities are of uncertain clinical significance and
      generally lessen with exercise. The normal exercise tolerance without symptoms or
      ECG changes suggests that myocardial perfusion is adequate during the physiologic
      stress of exercise in children up to 8 years after an arterial switch operation.

PMID- 8294698
TI  - Feasibility of generating hemodynamic pressure curves from noninvasive Doppler
      echocardiographic signals.
AB  - OBJECTIVES: This study was designed to determine the feasibility of Doppler
      generation of accurate, complete right ventricular and pulmonary artery pressure
      curves in patients with Doppler-measurable tricuspid and pulmonary regurgitation.
      BACKGROUND: Doppler-derived flow velocities have been used to assess right
      ventricular systolic pressure; pulmonary artery systolic, diastolic and mean
      pressures, and left ventricular systolic and diastolic pressures. Instantaneous
      gradient across any area of discrete narrowing is accurately derived using the
      simplified Bernoulli equation (4V2). Invasive catheterization is currently the
      only means of generating intracardiac pressure curves. Noninvasively derived
      pressure curves using Doppler echocardiography would be a considerable advance in
      the assessment of normal and pathologic cardiac hemodynamics. METHODS: Right
      ventricular and pulmonary artery pressure curves were generated in 18 of 22
      patients with measurable tricuspid and pulmonary valve regurgitation using
      superimposition of Doppler-measured tricuspid and pulmonary valve blood flow
      velocities on an assumed right atrial pressure. Doppler-measured right
      ventricular and pulmonary artery pressure curves were compared with simultaneous
      catheterization-measured curves. RESULTS: Doppler-derived pulmonary artery
      systolic pressure (Doppler PAP) correlated with simultaneous catheter-measured
      pulmonary artery pressure (Cath PAP) by the equation Doppler PAP = 0.92(Cath PAP)
      + 4.5, r = 0.98. Other Doppler-derived pressure measurements that correlated at
      near identity with the catheterization-measured corresponding measurement include
      Doppler-derived pulmonary artery mean pressure (Doppler mean PAP) [Doppler mean
      PAP = 0.85(Cath mean PAP) + 2.6, r = 0.97], and Doppler-derived right ventricular
      pressure (Doppler RVP) [Doppler RVP = 0.84(Cath measured RVP) + 7.9, r = 0.98].
      Doppler-derived pulmonary, artery diastolic pressure (Doppler PAP diast) did not
      correspond as well in this study [Doppler PAP diast = 0.45(Cath PAP diast) + 6.6,
      r = 0.83]. CONCLUSIONS: Clinically usable right ventricular and pulmonary artery
      pressure curves can be derived by superimposing Doppler-measured tricuspid and
      pulmonary valve blood flow velocities in patients with tricuspid and pulmonary
      valve regurgitation.

PMID- 8294699
TI  - Effective regurgitant orifice area: a noninvasive Doppler development of an old
      hemodynamic concept.
AB  - OBJECTIVES: The purpose of this study was to determine the feasibility, relation
      to other methods and significance of the effective regurgitant orifice area
      measurement. BACKGROUND: Assessment of the severity of valvular regurgitation
      (effective regurgitant orifice area) has not been implemented in clinical
      practice but can be made by Doppler echocardiography. METHODS: Effective
      regurgitant orifice area was calculated by Doppler echocardiography as the ratio
      of regurgitant volume/regurgitant jet time-velocity integral and compared with
      color flow Doppler mapping, angiography, surgical classification, regurgitant
      fraction and variables of volume overload. RESULTS: In 210 consecutive patients
      examined prospectively, feasibility improved from the early to the late
      experience (65% to 95%). Effective regurgitant orifice area was 28 +/- 23 mm2
      (mean +/- SD) for aortic regurgitation (32 patients), 22 +/- 13 mm2 for
      ischemic/functional mitral regurgitation (50 patients) and 41 +/- 32 mm2 for
      organic mitral regurgitation (82 patients). Significant correlations were found
      between effective regurgitant orifice and mitral jet area by color flow Doppler
      mapping (r = 0.68 and r = 0.63, p < 0.0001, respectively) and angiographic grade
      (r = 0.77, p = 0.0004). Effective regurgitant orifice area in surgically
      determined moderate and severe lesions was markedly different in mitral
      regurgitation (35 +/- 12 and 75 +/- 33 mm2, respectively, p = 0.009) and in
      aortic regurgitation (21 +/- 8 and 38 +/- 5 mm2, respectively, p = 0.08). Strong
      correlations were found between effective regurgitant orifice area and variables
      reflecting volume overload. A logarithmic regression was found between effective
      regurgitant orifice area and regurgitant fraction, underlining the
      complementarity of these indexes. CONCLUSIONS: Calculation of effective
      regurgitant orifice area is a noninvasive Doppler development of an old
      hemodynamic concept, allowing assessment of the lesion severity of valvular
      regurgitation. Feasibility is excellent with experience. Effective regurgitant
      orifice area is an important and clinically significant index of regurgitation
      severity. It brings additive information to other quantitative indexes and its
      measurement should be implemented in the comprehensive assessment of valvular
      regurgitation.

PMID- 8294700
TI  - Dietary arginine prevents atherogenesis in the coronary artery of the
      hypercholesterolemic rabbit.
AB  - OBJECTIVES: This study was designed to test the hypothesis that long-term oral
      supplementation of dietary L-arginine (to provide a sustained elevation of nitric
      oxide activity) would inhibit atherogenesis in hypercholesterolemic rabbits, as
      assessed by histomorphometric measurements. BACKGROUND: Endothelium-derived
      nitric oxide inhibits a number of processes that are critical in atherogenesis.
      Hypercholesterolemia reduces endothelial nitric oxide activity, and we postulate
      that this may promote atherogenesis. This reduction in nitric oxide activity can
      be reversed acutely by intravenous infusion of L-arginine, the precursor of
      nitric oxide. We show that dietary supplementation of L-arginine abrogates the
      development of coronary atheroma in hypercholesterolemic rabbits. METHODS: Male
      New Zealand White rabbits were fed normal rabbit chow, 1% cholesterol chow or 1%
      cholesterol chow with dietary arginine or methionine supplementation to increase
      their intake of these amino acids sixfold. After 1 or 10 weeks of dietary
      intervention, the left main and left anterior descending coronary arteries were
      harvested for histologic study. Plasma cholesterol measurements were elevated to
      the same degree in all groups of rabbits receiving the 1% cholesterol diet,
      whereas plasma arginine levels were doubled in the arginine-treated group. High
      density lipoprotein (HDL) cholesterol values were not affected by arginine
      treatment. RESULTS: In rabbits receiving the 1% cholesterol diet, with or without
      methionine supplementation, light and electron microscopy revealed a marked
      increase from 1 to 10 weeks in the intimal accumulation of macrophages,
      associated with an increase in the intimal area of the left main coronary artery.
      By contrast, in arginine-treated hypercholesterolemic rabbits, there was a near
      absence of adherent monocytes and tissue macrophages and no progression of
      intimal thickness from 1 to 10 weeks. CONCLUSIONS: Dietary supplements of L
      arginine prevent intimal thickening in the coronary arteries of
      hypercholesterolemic rabbits. This antiatherogenic effect is not due to an
      alteration in plasma total cholesterol, HDL cholesterol or caloric or nitrogen
      balance. The data are consistent with the hypothesis that nitric oxide has
      antiatherogenic properties.

PMID- 8294701
TI  - Preservation of regional myocardial function and myocardial oxygen tension during
      acute ischemia in pigs: comparison of selective synchronized suction and
      retroinfusion of coronary veins to synchronized coronary venous retroperfusion.
AB  - OBJECTIVES: The efficacy of selective synchronized suction and retroinfusion of
      coronary veins was compared with synchronized coronary venous retroperfusion in
      preventing ischemic reduction of regional myocardial function and myocardial
      oxygen tension. BACKGROUND: Because incomplete protection by synchronized
      coronary venous retroperfusion during ischemia might result from nonselective
      retroinfusion and only passive drainage of the veins, a suction device was added
      to a retroinfusion system. METHODS: Regional myocardial function (ultrasonic
      crystals) and myocardial oxygen tension (polarographic electrodes) were studied
      in 30 pigs during 10-min occlusion of the left anterior descending coronary
      artery (ischemia), followed by reperfusion. During ischemia, group A (n = 10) was
      supported by selective synchronized suction and retroinfusion; group B (n = 10)
      was supported by synchronized coronary venous retroperfusion, and group C (n =
      10) was not supported by retroinfusion. RESULTS: In group A, subendocardial
      segment shortening decreased from 21 +/- 4% (mean +/- SD) before ischemia to 11
      +/- 5% during ischemia. In contrast, systolic dyskinesia was observed in group B
      (-2 +/- 4%, p < 0.001) and group C (-2 +/- 5%, p < 0.001). During ischemia, the
      decrease in intramyocardial oxygen tension was less pronounced in group A (41 +/-
      15 vs. 27 +/- 12 mm Hg) than in group B (40 +/- 10 vs. 19 +/- 10 mm Hg, p = 0.1)
      or group C (33 +/- 11 vs. 12 +/- 8 mm Hg, p = 0.002). During ischemia, myocardial
      surface oxygen tension was preserved > 0 mm Hg only in group A. CONCLUSIONS:
      Preservation of regional myocardial function and myocardial oxygen tension was
      substantially higher by selective synchronized suction and retroinfusion of
      coronary veins than by synchronized coronary venous retroperfusion in pigs.

PMID- 8294702
TI  - Cardioprotective effects of ischemic preconditioning can be recaptured after they
      are lost.
AB  - OBJECTIVES: We sought to determine whether the cardioprotective effects of
      ischemic preconditioning can be reinstated once they are lost in a rat model of
      coronary occlusion. BACKGROUND: We have shown in a previous study that the
      cardioprotective effects of preconditioning are lost if there is a time lag (> or
      = 1 h) between the preconditioning and sustained coronary occlusion events in the
      rat. However, whether the beneficial effects of preconditioning can be regained
      once they are lost in this model is unknown. METHODS: Twenty-eight rats were
      randomized to one of four groups. Group 1 (control group) underwent 90 min of
      coronary occlusion without preconditioning. Group 2 had preconditioning (three
      cycles of 3 min of coronary occlusion and 5 min of reperfusion) that was
      immediately followed by 90 min of coronary occlusion. In group 3, 90 min of
      occlusion was delayed by 1 h after preconditioning. In group 4, preconditioning
      was repeated 1 h after a first preconditioning sequence, followed by 90 min of
      occlusion. After 4 h of reperfusion, the area at risk was delineated by
      intravenous injection of blue dye during a brief coronary occlusion, and the area
      of necrosis was determined by the triphenyltetrazolium chloride technique.
      RESULTS: Myocardial infarct size, expressed as a percent of the anatomic area at
      risk in groups 1 and 3 averaged 44.1 +/- 6.9% (mean +/- SEM) and 49.9 +/- 6.9%,
      respectively. In contrast, groups 2 and 4 (12.1 +/- 3.2% and 10.1 +/- 2.6%,
      respectively) had a significantly smaller infarct size (p < 0.01 vs. groups 1 and
      3). The incidence of ventricular tachycardia during the 90 min of coronary
      occlusion in both groups 2 and 4 (14.3%, p < 0.005 and 28.6%, p < 0.05,
      respectively) was significantly lower than in groups 1 and 3 (100% in both
      groups). CONCLUSIONS: Repeat preconditioning at 1 h was capable of recapturing
      the cardioprotective effects of preconditioning on both infarct size and
      ventricular arrhythmia.

PMID- 8294703
TI  - Effects of dobutamine and arbutamine on regional myocardial function in a porcine
      model of myocardial ischemia.
AB  - OBJECTIVES: The present study was performed to determine the mechanisms for
      catecholamine-induced wall motion abnormalities and to compare the diagnostic
      efficacy of two catecholamines: arbutamine and dobutamine. BACKGROUND:
      Catecholamine stress echocardiography is used to induce regional wall motion
      abnormalities for the detection of coronary artery disease, but the mechanism by
      which these abnormalities occur is unknown. METHODS: Ten pigs were instrumented
      with left circumflex coronary artery ameroid constrictors, sonomicrometers to
      measure transmural wall thickening in the left circumflex (ischemic) and left
      anterior descending (control) coronary artery beds and a pressure gauge to
      measure left ventricular pressure and its first derivative (dP/dt). Myocardial
      blood flow was measured by microspheres. RESULTS: At 38 +/- 6 days (mean +/- SEM)
      after surgery, percent wall thickening was normal at rest in both beds but
      abnormal in the left circumflex coronary artery bed during atrial pacing. These
      findings were associated with reduced myocardial blood flow in the ischemic bed
      during atrial pacing. Dobutamine infusion increased percent wall thickening, with
      no differences between the two beds (p = 0.63). In contrast, arbutamine infusion
      increased percent wall thickening only in the nonischemic bed, with no effect on
      percent wall thickening in the ischemic bed (p = 0.03). Although the
      endocardial/epicardial blood flow ratio tended to be reduced in the left
      circumflex artery bed during catecholamine infusion (p = 0.07), both agents were
      similar in this effect. Despite differences in function between the beds, there
      was no difference in transmural myocardial blood flow between the two beds during
      catecholamine infusion. When examined at matched metabolic demands, arbutamine
      elicited greater differences in percent wall thickening than dobutamine between
      the two beds (p < 0.01). CONCLUSIONS: Arbutamine was able to provoke regional
      differences in function in a manner superior to dobutamine. This occurred
      independently of altered transmural myocardial blood flow or differences in
      hemodynamic effects between the agents. Differences in their inotropic properties
      may be important in explaining their different effects on ischemic myocardium.

PMID- 8294704
TI  - Prevention of arterial thrombosis by a monoclonal antibody against the 100 to 109
      amino acid sequence stretch of the beta-subunit of the human platelet fibrinogen
      receptor: a comparative study with low dose aspirin.
AB  - OBJECTIVES: The aim of this study was to compare, in dogs, the antithrombotic
      activity of aspirin and the murine monoclonal antibody P37, which inhibits
      platelet aggregation and fibrinogen binding to activated platelets. BACKGROUND:
      The antithrombotic activity of P37 has been somewhat predictable, given its in
      vitro platelet antiaggregating activity and localization at or very near the
      fibrinogen binding site in the platelet fibrinogen receptor, the glycoprotein
      IIb/IIIa or integrin alpha IIb-beta 3. METHODS: The monoclonal antibody P37 of
      the immunogamma-globulin-1 isotype was prepared according to previously described
      immunization and fusion protocols and screening assays. To compare its
      antiaggregating capacity with that of aspirin, experimental thrombosis was
      induced in all dogs by means of direct current applied to the carotid artery.
      Autologous platelets had previously been labeled with indium-111 oxine. The dogs
      were assigned to three groups: group I (n = 18) was the control group; group II
      (n = 12) was treated orally with 5 mg of aspirin/kg body weight per day for 7
      days before induction of thrombosis, and group III (n = 10) was treated
      intravenously with a single dose of P37 (0.8 mg/kg). RESULTS: The indium-111
      oxine activity deposited in the thrombi was 12.94 +/- 12.83% (mean +/- SD) in
      group I, 3.55 +/- 2.99% in group II and 0.03 +/- 0.03% in group III. The
      differences between groups were always statistically significant (p < 0.05).
      CONCLUSIONS: We conclude that a single dose (0.8 mg/kg) of P37 in a canine model
      of arterial thrombosis is approximately 100 times more efficient than the
      administration of aspirin (5 mg/kg per day) in preventing platelet deposition
      during thrombus formation.

PMID- 8294706
TI  - Selective aortic perfusion and oxygenation: an effective adjunct to external
      chest compression-based cardiopulmonary resuscitation.
AB  - OBJECTIVES: The purpose of this study was to compare the perfusion pressure and
      rate of return of spontaneous circulation produced by standard advanced cardiac
      life support with that resulting from advanced cardiac life support with
      simultaneous aortic occlusion and proximal infusion with oxygenated fluid.
      BACKGROUND: Cardiopulmonary resuscitation based solely on external chest
      compression is unable to achieve return of spontaneous circulation in most
      patients with cardiac arrest. Adjunctive therapies that enhance myocardial oxygen
      supply may improve outcomes. METHODS: We conducted a prospective, randomized
      study in mongrel dogs using a fibrillatory model of cardiac arrest with a 20-min
      arrest time. Dogs were randomized to two groups. Aortic arch and right atrial
      micromanometers were placed to measure intravascular pressure. Manual external
      chest compression was used and standardized to an esophageal pulse pressure of 50
      mm Hg. Two minutes after initiation of advanced cardiac life support, selective
      aortic perfusion and oxygenation were initiated in dogs assigned to one group by
      inflation of an occluding balloon in the descending aorta and infusion of 450 ml
      of ultrapurified polymerized bovine hemoglobin through a large bore central
      infusion port. RESULTS: Maximal aortic pressure during standard advanced cardiac
      life support was 42 +/- 23 (mean +/- SD) versus 69 +/- 28 mm Hg during advanced
      cardiac life support with selective aortic perfusion and oxygenation. Maximal
      coronary perfusion pressure during standard therapy was 33 +/- 21 versus 62 +/-
      26 mm Hg during combined therapy. Only 2 of 10 dogs receiving standard therapy
      had return of spontaneous circulation versus 6 of 7 dogs receiving combined
      therapy. Balloon occlusion alone did not increase perfusion pressure
      significantly. CONCLUSIONS: The use of selective aortic perfusion and oxygenation
      increases aortic and coronary perfusion pressures during cardiopulmonary
      resuscitation, resulting in a large increase in the rate of return of spontaneous
      circulation. This technique may be an effective adjunct to advanced cardiac life
      support based on any method of external chest compression and may improve the
      poor prognosis of patients with cardiac arrest.

PMID- 8294705
TI  - Adenosine triphosphate-sensitive potassium channel blocking agent ameliorates,
      but the opening agent aggravates, ischemia/reperfusion-induced injury. Heart
      function studies in nonfibrillating isolated hearts.
AB  - OBJECTIVES: This study was conducted to elucidate the role of the adenosine
      triphosphate (ATP)-sensitive potassium channel blocking agent glibenclamide and
      the opener cromakalim in the mechanism of reperfusion-induced injury. BACKGROUND:
      Recently, ATP-sensitive potassium channel openers have been proposed to reduce
      ischemia/reperfusion-induced injury, including arrhythmias and heart function.
      Thus, one might hypothesize that pharmacologic agents that enhance the loss of
      potassium ions in the myocardium through ATP-sensitive potassium channels would
      be arrhythmogenic, and agents that interfere with tissue potassium ion loss would
      be antiarrhythmic. METHODS: Isolated "working" guinea pig hearts and phosphorus
      31 nuclear magnetic resonance spectroscopy were used to study the recovery of
      myocardial function and phosphorus compounds after 30, 40 and 50 min of
      normothermic global ischemia followed by reperfusion in untreated control and
      glibenclamide- and cromakalim-treated groups. RESULTS: After 30 min of ischemia,
      1, 3, 10 and 30 mumol/liter of glibenclamide dose-dependently reduced the
      incidence of reperfusion-induced ventricular fibrillation (total) from its
      control value of 92% to 75%, 33% (p < 0.05), 33% (p < 0.05) and 42% (p < 0.05),
      respectively. The incidence of ventricular tachycardia followed the same pattern.
      A reduction of arrhythmias was also observed after 40 and 50 min of ischemia
      followed by reperfusion in the glibenclamide-treated hearts. Cromakalim, at the
      same concentrations, did not reduce the incidence of reperfusion-induced
      arrhythmias. During reperfusion, glibenclamide (3 and 10 mumol/liter) improved
      the recovery of coronary blood flow, aortic flow, myocardial contractility and
      tissue ATP and creatine phosphate content, but cromakalim failed to ameliorate
      the recovery of postischemic myocardium compared with that in the drug-free
      control hearts. CONCLUSIONS: The preservation of myocardial potassium ions and
      phosphorus compounds by glibenclamide can improve the recovery of postischemic
      function, but the use of ATP-sensitive potassium channel openers as
      antihypertensive or antiarrhythmic agents may be of particular concern in those
      postinfarction patients who are known to be at high risk for sudden cardiac
      death.

PMID- 8294707
TI  - Markedly different effects on ventricular remodeling result in a decrease in
      inducibility of ventricular arrhythmias.
AB  - OBJECTIVES: The purpose of this study was to determine whether the type and
      extent of ventricular remodeling after infarction influence inducibility of
      ventricular arrhythmias after infarction. BACKGROUND: Although serious
      ventricular arrhythmias after infarction are related to ventricular dysfunction,
      the relation between inducibility of ventricular arrhythmias and ventricular
      remodeling remains incompletely understood. METHODS: Rats that survived ligation
      of the left anterior descending coronary artery (n = 218) were randomized to
      receive placebo (saline solution) or captopril or propranolol therapy and were
      followed up for 5 weeks. Hemodynamic and neurohumoral blood measurements were
      obtained, and therapy was stopped. Two days later, susceptibility to ventricular
      arrhythmias was assessed by programmed electrical stimulation, and hearts were
      prepared for pathologic studies. RESULTS: Placebo-treated rats with a large
      myocardial infarction had ventricular dysfunction, marked neurohumoral
      activation, ventricular enlargement (endocardial circumference 16 +/- 3 [mean +/-
      SD] to 20 +/- 4 mm, p < 0.05) and increased cardiac fibrosis (volume density of
      collagen 2.3 +/- 0.8% to 5.6 +/- 2.4%, p < 0.05). In many rats this resulted in
      easily inducible ventricular arrhythmias (inducibility quotient 4.9 +/- 2.2).
      Captopril attenuated the development of ventricular dysfunction, neurohumoral
      activation, ventricular hypertrophy and dilation (endocardial circumference 18 +/
      3 mm) and cardiac fibrosis (3.1 +/- 0.8%, p < 0.05). These modifications were
      accompanied by decreased inducibility of ventricular arrhythmias (inducibility
      quotient 1.1 +/- 2.0, p < 0.05). Propranolol did not prevent ventricular
      dysfunction, had variable effects on neurohumoral activation and led to increased
      ventricular dilation (endocardial circumference 25 +/- 4 mm, p < 0.05) and
      cardiac fibrosis (7.7 +/- 1.2%, p < 0.05). Nevertheless, these morphologic
      changes led to decreased inducibility of ventricular arrhythmias (inducibility
      quotient 2.2 +/- 2.5%, p < 0.05). CONCLUSIONS: This study indicates that the
      inducibility of ventricular arrhythmias can be reduced as a result of markedly
      different effects on ventricular remodeling, indicating that the relation between
      ventricular remodeling, arrhythmias and survival is more complex than previously
      thought.

PMID- 8294708
TI  - Nonlinearity of the left ventricular end-systolic wall stress-velocity of fiber
      shortening relation in young pigs: a potential pitfall in its use as a single
      beat index of contractility.
AB  - OBJECTIVES: We sought to evaluate in the young heart the primary assumptions on
      which the current use of the mean "velocity of fiber shortening corrected for
      heart rate" as a noninvasive index of contractility are based. BACKGROUND: End
      systolic wall stress-velocity of fiber shortening relation has been applied as a
      single-beat, load-independent index of contractility in children. This use is
      based on poorly validated assumptions of linearity, parallel shifts with changing
      contractile state and inotropic sensitivity of the end-systolic wall stress
      velocity of fiber shortening relation. METHODS: In eight anesthetized young
      piglets, 5F mciromanometric catheters were placed in the ascending aorta and
      balloon occlusion catheters in the descending aorta. End-systolic wall stress and
      velocity of fiber shortening were calculated from aortic pressure and M-mode
      echocardiography under six conditions: in three contractile states 1) baseline,
      2) increased contractility during dobutamine infusion (10 micrograms/kg per min),
      and 3) decreased contractility after propranolol injection (1 mg/kg), each at two
      afterload states (normal and increased load by partial aortic occlusion).
      RESULTS: Dobutamine increased and propranolol decreased afterload-matched
      velocity of fiber shortening corrected for heart rate significantly to 140% and
      77% of baseline, respectively. However, the slope of end-systolic wall stress
      velocity of fiber shortening relation was much greater (251% of baseline) during
      dobutamine infusion, which also significantly decreased wall stress, and was much
      less (27% of baseline) after propranolol injection, which increased wall stress.
      CONCLUSIONS: The velocity of fiber shortening corrected for heart rate did change
      predictably with changes in contractility and as such can be used noninvasively
      in the temporal evaluation of individual patients undergoing therapeutic
      interventions or to define the natural history of a disease process. However, the
      relation on which it is based is not defined by parallel straight lines across
      contractile states, so that abnormal single point measurements may reflect only
      the nonlinearity of the relation rather than abnormalities in contractility.
      Thus, we recommend that the end-systolic wall stress-velocity of fiber shortening
      relation should not be used as a single-beat index of contractility.

PMID- 8294709
TI  - Perspectives on invasive cardiology: the 24th Louis F. Bishop Lecture.
AB  - The fast growing and complex field of invasive cardiology offers a host of
      opportunities and challenges for the clinician. Scientific and technical advances
      ranging from molecular biology to microtechnology are changing how physicians
      make decisions concerning treatment of coronary artery disease, myocardial
      infarction, unstable angina and electrophysiologic dysfunction. The economic
      impact and ethical implications presented by these developments contribute to the
      difficulty of achieving optimal therapeutic solutions for individual patients.

PMID- 8294710
TI  - Should all patients undergo transesophageal echocardiography before electrical
      cardioversion of atrial fibrillation?
AB  - The management of anticoagulant therapy in patients with atrial fibrillation
      undergoing electrical cardioversion remains controversial, largely because of
      inadequate studies demonstrating risk or benefit, a relatively inconvenient
      anticoagulation management strategy and the increasing use of transesophageal
      echocardiography. Recent investigations into the potential mechanisms involved in
      the development of thrombus and systemic embolism in patients undergoing
      electrical cardioversion of atrial fibrillation may provide insight into
      underlying predisposing factors, with subsequent modification of management
      strategies. Conventional wisdom suggests that preexisting thrombus is responsible
      for thromboembolic events after cardioversion. However, development of a
      thrombogenic milieu after cardioversion, particularly in the left atrial
      appendage, may also be an important predisposing factor. To protect against both
      potential mechanisms of embolization, these data support therapeutic
      anticoagulation for all patients with atrial fibrillation of > 2 days in duration
      from the time of, as well as after cardioversion for a total of 4 weeks,
      undergoing cardioversion, even in the absence of thrombus on echocardiography.
      Therefore, the role of transesophageal echocardiography in this setting should be
      to enable early cardioversion if atrial thrombus is excluded and to identify high
      risk patients with atrial thrombi so as to postpone cardioversion and avoid the
      risk of embolization. Ultimately, however, a controlled, randomized and
      prospective clinical trial will be required to compare conventional management
      with a transesophageal echocardiography-guided strategy.

PMID- 8294711
TI  - Redundant publication.

PMID- 8294712
TI  - President's page: new medicine from old--hirudin and the leech.

PMID- 8294713
TI  - Notice of duplicate publication.

PMID- 8294714
TI  - Estimating cardiac risk before major vascular surgery.

PMID- 8294715
TI  - Signal-averaged P wave duration and atrial fibrillation.

PMID- 8294716
TI  - Same-day surgical admission.

PMID- 8294717
TI  - Dietary supplementation with vitamins C and E inhibits in vitro oxidation of
      lipoproteins.
AB  - The oxidative modification of lipoproteins has been implicated in atherogenesis,
      suggesting a protective role of circulating antioxidants. Vitamin C (ascorbic
      acid, 1 g/day) and vitamin E (dl alpha-tocopheryl acetate, 800 IU/day) were
      administered to healthy female and male volunteers. Lipoproteins with density <
      1.063 g/mL were isolated from serum before and after vitamin supplementation and
      incubated with copper (Cu) or mononuclear cells (MC) plus Cu. Administration of
      vitamins C and E together to 4 subjects for 10 days resulted in a 57% (range 40
      72%) decrease in Cu-catalyzed production of thiobarbituric acid reactive
      substances (TBARS) under the following conditions of assay: incubation times of 0
      8 hours, Cu concentrations of 0-10 microM lipoprotein protein concentrations of
      0.1-0.5 mg/mL. Decreases in other parameters of lipoprotein oxidation, i.e,,
      electrophoretic mobility, production of conjugated dienes and modification of
      amino groups, were also observed. Vitamin E administration alone produced a 52%
      inhibition and vitamin C alone a 15% inhibition of TBARS formation. Vitamins C
      and E supplementation resulted in a 78% decrease in the susceptibility of
      lipoproteins to MC-mediated oxidation. There was a strong inverse correlation (r
      = -0.64, p < 0.0007) between vitamin E levels in the lipoproteins and TBARS
      production in samples from 12 subjects administered vitamins C and E. In 3
      individuals vitamin E levels remained low and in 2 of these subjects there was no
      effect of vitamins C and E administration on TBARS production. These results
      suggest a protective role of antioxidant vitamins and significant individual
      variability in response.

PMID- 8294718
TI  - Hepatic fatty acid-binding protein mRNA is regulated by growth hormone.
AB  - Hepatic fatty acid-binding protein (FABP) is one of several abundant proteins
      which may participate in fatty acid uptake and utilization. Using differential
      hybridization to screen for growth hormone-responsive gene products, a
      complementary deoxyribonucleic acid (cDNA) was isolated which proved to be a
      hepatic FABP cDNA fragment. Hypophysectomy caused a 60% reduction in hepatic FABP
      messenger ribonucleic acid (mRNA) levels in rat liver, and growth hormone
      administration to hypophysectomized rats resulted in restoration of the
      expression of hepatic FABP mRNA. Other pituitary hormones did not alter these
      changes in expression. The response to growth hormone occurred within 4 hours of
      administration. During development, expression of hepatic FABP mRNA in rat liver
      was low in late fetal life, with increases to 40% of adult values by day 2 of
      life. Significant increases to adult levels did not occur until after day 25,
      when weaning is essentially completed. Alteration of hepatic FABP mRNA expression
      by growth hormone in rat liver may be important in the complex regulation of
      fatty acid uptake and metabolism.

PMID- 8294720
TI  - Fatty acids in some common food items in Canada.
AB  - Fat content and fatty acid (FA) composition of 100 common items in 17 food
      categories from the Canadian retail market were determined. Of these, 52 samples
      were made from partially hydrogenated fat. Their fat (in parentheses) and trans
      FA levels were as follows: breads (3.7% fat) 15.7%, hamburger buns (5.5% fat)
      26.3%, cakes (8.7-36.7% fat) 10.1-25.7%, candies/chocolates (27.1% fat) 11.1%,
      cereals (1.3-12.9% fat) 9.2-33.7%, cookies (5.0-40.5% fat) 7.6-38.7%, crackers
      (9.2-33.0% fat) 13.8-35.4%, donuts (16.6-29.6% fat) 27.7-32.7%, french fries (pre
      cooked) (4.3-4.5% fat) 32.8-42.8%, muffins (12.5-23.7% fat) 16.5-24.2%, pizza
      crusts (6.0-7.2% fat) 22.1-28.8%, shortenings (100% fat) 17.4-20.2%, potato chips
      (33.2-40.0% fat) 29.7-39.7%, and corn chips (25.0-34.2%) 29.9-33.9%. Generally
      the sum of saturated and trans FA in the food items made with partially
      hydrogenated fat was higher than that of the corresponding food items made with
      unhydrogenated oils. The higher levels of saturates plus trans were at the
      expense of the essential fatty acids (EFA). The high-fat foods, such as cakes,
      cookies, crackers, donuts and potato chips, made with partially hydrogenated fat,
      were substantially lower in EFA and contained relatively higher levels of trans
      polyunsaturated fatty acids (PUFA). In some samples of potato chips and french
      fries, the level of trans PUFA was almost the same or more than the sum of
      linoleic and linolenic acids.

PMID- 8294719
TI  - Influence of dietary medium- and long-chain triglycerides on fat deposition and
      lipogenic enzyme activities in rats.
AB  - The present study investigates fat deposition, variances of fatty acid (FA)
      composition, and lipogenic enzyme activities through dietary medium- and long
      chain triglyceride (MCT and LCT) supplementation in growing rats. Eighteen male
      Wistar rats were divided into three groups and fed isocalorically for 4 weeks
      with control (based on AIN 76), MCT (C8:0 26%), or LCT (corn oil 25%) diets.
      Compared to the control group with 0.28 +/- 0.01, feed efficiency was lower in
      the MCT rats and greater in the LCT rats (0.24 +/- 0.01 and 0.33 +/- 0.01,
      respectively). Weights of perirenal and epididymal adipose tissue pads of the MCT
      rats were similar to those of the control group, but were significantly lower
      than those of the LCT group. Whole-body carcass components data of MCT rats
      showed the decrease in moisture and protein contents compared to those of control
      and LCT rats. Fat content of LCT rats was 25-30% higher than those of the MCT and
      control group. Glucose-6-phosphate dehydrogenase, citrate cleavage enzyme, and
      malic enzyme activities of liver and epididymal adipose tissue were markedly low
      in LCT rats. In the MCT group, however, lipogenic enzyme activities were not
      suppressed, and malic enzyme activity was drastically increased. FA composition
      of whole-body triglycerides and epididymal adipose tissue in MCT rats showed that
      C16:0 and C16:1 levels were higher than those of the LCT rats. In contrast, FA
      composition of the LCT group presented high C18:2 content.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8294721
TI  - Preparation of a dietary fiber mixture derived from different sources and its
      metabolic effects in rats.
AB  - In this study we analyzed a commercial dietary fiber blend known as Fiber-Plus
      and a dietary fiber mixture (DFM) prepared in our lab (10% apple pectin, 10%
      orange pectin, 36% locust bean gum and 44% corncob composed of 56% fiber). DFM
      provided greater inhibition of starch digestion and glucose absorption (p < 0.05)
      than did Fiber-Plus. DFM was also found to be significantly more efficient (p <
      0.05) than Fiber-Plus at reducing the glycemic response following starch loading.
      Rats fed DFM or corncob demonstrated a much lower glycemic response following a
      test meal as compared to those fed a fiber-free diet. Both fiber sources
      decreased fasting cholesterol and triglyceride concentrations; transit time was
      shortened and fecal values were higher than those of controls. beta-glucuronidase
      activity in intestinal segment contents and feces was lower in rats fed fiber. We
      conclude that DFM is effective in controlling plasma glucose and lipid levels.
      Corncob, a novel fiber source, could be beneficial in the treatment of
      gastrointestinal tract disorders and in the elimination of carcinogenic elements.

PMID- 8294722
TI  - Defining the year 2000 fruit and vegetable goal.
AB  - Various nutrition guidelines recommend increased consumption of fruits and
      vegetables (F+V); a Year 2000 goal targets five or more daily servings of F+V.
      Decisions are needed regarding how to define F+V to facilitate measurement of
      goal achievement. Four alternative definitions (narrow and broad, each with and
      without legumes) were developed and applied to food frequencies from 133 children
      and 211 parents. Results varied by definition. Mean intake met the goal of five
      or more daily servings regardless of definition and exceeded it for both broad
      definitions by children and both broad definitions and the narrow definition with
      legumes for adults. Median intakes met the goal for all definitions except for
      children with the narrow definition without legumes, and exceeded it for children
      with both broad definitions and for adults with the broad definition with
      legumes. These differences by definition indicate that a clear definition of F+V
      is needed.

PMID- 8294723
TI  - Relationship of dietary intake to hospital admission for coronary heart and
      vascular disease: the NHANES II national probability study.
AB  - After excluding 2,908 subjects (25% of the cohort) whose diets had changed,
      possibly as a consequence of disease discovery, in 8,679 individuals from the
      NHANES II national probability study, our specific aim was to determine which
      nutritional factors were significant independent contributors to overnight
      hospitalization with coronary heart and vascular disease (CHD). Covariance
      adjustments were made for multiple sociodemographic, educational, geographic
      factors, total cholesterol, high-density lipoprotein cholesterol (HDL-C), race,
      age, sex, and relative ponderosity (obesity). After these adjustments, linoleic
      acid (p = 0.049) and alcohol (p = 0.017) were independently inversely associated
      with CHD hospitalizations; cigarette smoking (p = 0.054) was positively
      associated. Relative risk for CHD hospitalization was 1.0 for linoleate 0-6
      g/day, 0.72 for 6-11.59 g/day, and 0.49 for > or = 11.6 g/day, p < or = 0.01.
      Relative risk for CHD hospitalization was 1.0 for no coffee intake, 0.6 for
      regular coffee, 1.8 for regular coffee plus decaffeinated coffee, 2.6 for
      decaffeinated coffee, and 5.2 when decaffeinated coffee was drunk by virtue of
      physicians' advice, p < or = 0.001. Unlike our extensive exclusions (25% of the
      cohort) for diet change, we did not exclude any subjects on the basis of self
      directed or physician-recommended changes in smoking habits of initiation of
      decaffeinated coffee use, following, or as a consequence of disease discovery. We
      speculate that the relationship of decaffeinated coffee to CHD reflects behavior
      change after CHD hospitalization. Dietary cholesterol (p = 0.038) was an
      independent positive predictor of serum total cholesterol.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8294724
TI  - Nutrition status of the elderly in Anogia, Crete, Greece.
AB  - General health and nutritional status of 167 free-living elderly Greek (aged 65
      91 years) were assessed. The most prevalent diseases/symptoms encountered were
      related to respiratory, gastrointestinal, musculoskeletal and vascular systems
      (hypertension). Most subjects were socially active. Body mass index was < 20 and
      > 25 Kg/m2 in 7 and 57% of the subjects, respectively. Systolic blood pressure
      was significantly higher in women than in men, and as a group, 18 and 42%,
      respectively, had diastolic blood pressures > 90 and systolic blood pressures >
      160 mmHg. Anemia and hypoalbuminemia were detected in < 5% of the population.
      Total fat intake was 40-45% of total energy intake and most of it came from
      monounsaturated fat. Hypercholesterolemia (> 6 mmol/L) was present in 32% of
      subjects. The percentages of men who smoked (66%) or drank (68%) were
      significantly higher than those of women (2 and 1%, respectively). Dietary intake
      data were compared with US recommended dietary allowances (RDA) for elderly.
      Daily energy and protein intakes were lower than the US RDA levels; calcium
      intake was > 50% of the US RDA, while magnesium and vitamin B6 levels were < 50%
      of the US RDA. Vitamin C intake was much higher than that of the US RDA. Mean
      thiamin, vitamin A, riboflavin and iron intakes were below the US RDA, while
      fiber intake was < 50% of the corresponding US estimate. Phosphorus was higher
      than the US RDA in men, while lower for women. Sodium intakes exceeded those
      recommended, while potassium levels were higher than those recommended in males,
      and lower in females.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294725
TI  - Symptom and personality profiles of young adults from a college student
      population with self-reported illness from foods and chemicals.
AB  - Despite much debate over a presumptively somatic vs psychological etiology of
      nonatopic food and chemical sensitivities, little systematic research has
      addressed the issues. The present study investigated self-reported illness from
      several common foods (wheat, dairy, eggs) and chemicals (pesticide, car exhaust,
      paint, perfume, new carpet), symptom patterns, and psychological profiles of a
      sample of young adult college students (n = 490, age 19.4 +/- 2.4, 52% female/48%
      male). Subjects were divided into 4 groups on the basis of sample medians for
      frequency of illness from the foods (FI) and chemicals (CI); high FI with high CI
      (FI/CI), high FI alone, high CI alone, and NOILL (low FI and CI). FI was
      associated with more defensiveness (denial of negativity) while CI was linked
      with more shyness (avoidance of novelty). Women outnumbered men in all groups
      (FI/CI: 61%; FI: 80% CI: 55%) except the NOILL (40% women). Nevertheless, the
      FI/CI, FI, and/or CI groups still had significantly higher total symptom scores
      as well as more indigestion, headache, and memory trouble than did the NOILL
      group, even after depression, anxiety, shyness, defensiveness, and gender were
      covaried. The illness groups reported significantly more limitation of foods that
      mobilize endogenous opioids or generate exogenous opioids (sweets, fats, bread)
      as well as more illness from opiate drugs, small amounts of beverage alcohol, and
      late meals. Nasal symptoms from pollens or animals were more common in the FI/CI
      (42%) and CI (42%) than in FI (26%) or NOILL (28%) groups. Premenstrual tension
      syndrome and irritable bowel were also more common in the FI/CI group. The
      findings indicate that young adults outside the clinical setting who are
      relatively higher in FI and/or CI have distinctive symptom and psychological
      patterns. Covariate analyses suggest that important symptoms in FI and CI
      individuals such as indigestion, headache, and memory problems may occur in
      addition to rather than as simply part of emotional distress. The data are
      consistent with a previously hypothesized role of olfactory-limbic and
      hypothalamic pathways and with a time-dependent sensitization model for illness
      from foods and chemicals.

PMID- 8294726
TI  - Plasma glucose and insulin responses to bananas of varying ripeness in persons
      with noninsulin-dependent diabetes mellitus.
AB  - With progressive ripeness there is a decrease in starch and an increase in free
      sugar content of bananas. The starch also is considered to be poorly digestible.
      Therefore, we decided to study plasma glucose, serum insulin, C-peptide, and
      plasma glucagon responses to bananas with increasing degrees of ripeness. Seven
      male subjects with untreated noninsulin-dependent diabetes mellitus ingested 50 g
      carbohydrate as bananas of stage 4 (more yellow than green), 5 (yellow with green
      tip), 6 (all yellow), and 7 (yellow flecked with brown) ripeness. They also
      received 50 glucose on two occasions for comparative purposes. On a separate
      occasion water only was given as a control. The area responses were quantified by
      determining incremental areas using the water control as baseline. The mean
      glucose area following the 50 g glucose meals was 15.1 +/- 1.9 mM.h. After the
      ingestion of bananas of 4, 5, 6 and 7 ripeness the glucose area response was 42,
      41, 51 and 48% of that after glucose ingestion, respectively. The insulin area
      response following glucose meals was 888 pM.h. Responses to 4, 5, 6 and 7 bananas
      were 85, 70, 61, 85%, respectively, of that following glucose ingestion. C
      peptide data were similar to the insulin data. The glucagon area response was
      negative after glucose ingestion but was positive following banana ingestion. In
      summary, the glucose, insulin, C-peptide, and glucagon area responses varied
      little with ripeness of the bananas.

PMID- 8294727
TI  - Hypomagnesemia following correction of metabolic acidosis: a case of hungry
      bones.
AB  - Severe symptomatic hypomagnesemia (0.15 mmol/L [0.3 mEq/L]) and hypocalcemia
      (1.47 mmol/L [5.9 mg/dL]) occurred in a 4-week-old infant coincidental with
      correction of a severe renal tubular acidosis with alkali therapy. The patient
      had no evidence of gastrointestinal abnormality and magnesium (Mg) intake was
      adequate for age and weight. Extreme renal conservation of Mg was observed,
      supporting the presence of Mg depletion. We suggest that Mg depletion in this
      infant occurred due to acidosis-induced bone demineralization and that
      symptomatic hypomagnesemia was precipitated by rapid remineralization
      accompanying correction of systemic acidosis. This patient represents a novel
      case of hungry bone syndrome (HBS). Since HBS has not been described previously
      in patients with acidosis undergoing therapy, several other factors may have
      contributed to this patient's severe hypomagnesemia, namely, prematurity, twin
      status, severity of acidosis, rapidity of correction of acidosis, catch-up growth
      and calcium supplementation. Clinicians should be vigilant for HBS in infants
      with severe acidosis undergoing alkali therapy.

PMID- 8294728
TI  - Dietary regulation of copper absorption and storage in rats: effects of sodium,
      zinc and histidine-zinc.
AB  - Zinc (Zn) and L-histidine (His) are known competitors of intestinal copper (Cu)
      uptake. Sodium (Na) appears to be an enhancer of the luminal phase of Cu
      absorption. We investigated whether dietary treatment with these modifiers would
      alter Cu absorption and tissue stores of Zn and Cu in rats. Juvenile male rats
      were fed semipurified diets with adequate amounts of Cu, Zn and Na (Ctl), or with
      the addition of either excess Na (Hi Na), Zn (Hi Zn), or Zn plus His (Hi Zn+His)
      for 3 weeks. The jejunum was perfused in situ with 0.1 mM Cu, 1 mM His to
      determine Cu and water absorption rates. The lowest Cu absorption rate was
      observed in the Hi Zn+His group, and both the Hi Zn and Hi Zn+His had greater Cu
      accumulation in the small intestine than did Ctl or Hi Na rats. Hi Na had no
      effect on Cu transport. There was excess Cu accumulation in the kidneys of Hi
      Zn+His rats, and hepatic and kidney metallothioneins were also elevated. These
      results indicate that while a high Na intake does not affect Cu absorption,
      excess dietary Zn and His have greater effect than does Zn only in the limitation
      of Cu uptake.

PMID- 8294730
TI  - Congenital attenuation of the extensor tendon central slip.
AB  - A congenital attenuation of the central slip results in a flexion attitude of the
      affected digit that can be confused with more common conditions such as
      congenital trigger finger or camptodactyly. It is a mild form of congenital
      absence of the central slip. The diagnosis is discussed. Treatment consists of
      limited excision of the attenuated area and suturing of the normal components of
      the central slip. The author has treated five cases in the last 10 years.

PMID- 8294729
TI  - Regulation of iron absorption: proteins involved in duodenal mucosal uptake and
      transport.
AB  - Newly identified iron (Fe)-binding proteins isolated from both rat and human
      duodenal mucosa permit a better understanding of Fe absorption. Mucins bind Fe at
      acid pH to keep it soluble and available for absorption at the more alkaline pH
      of the duodenum; this explains the development of Fe deficiency in achlorhydric
      subjects. Integrin was identified on the surface of enterocytes in association
      with radioiron and is believed to facilitate the transfer of Fe through the
      microvillous membrane. Mobilferrin, a 56 kDa Fe-binding protein, was identified
      in enterocyte cytosol. It coprecipitates with integrin and appears in close
      association with integrin in the apical cytoplasm of absorptive cells. We
      postulate it accepts dietary Fe from integrin and acts as the shuttle protein
      from Fe in the cytoplasm. Since Fe in enterocytes remains in equilibrium with
      body stores, we postulate mucosal Fe uptake is regulated by the number of Fe
      binding sites either occupied or unoccupied by Fe on mobilferrin. Fe repletion of
      enterocytes from body stores is probably accomplished via transferrin receptors
      on the basal membranes of enterocytes. Increased transfer of Fe from blood into
      absorptive enterocytes occurs in Fe-replete animals to inhibit mucosal uptake of
      dietary Fe. Little transfer of Fe from plasma to enterocytes occurs in Fe
      deficiency. Enhanced mucosal transfer into the body occurs with increased body
      need for Fe. The exact mechanism for mucosal transfer of Fe into the plasma has
      not been defined but may also be mediated by an integrin.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8294731
TI  - Long-term results after the surgical treatment of Madelung's deformity: a case
      report.

PMID- 8294732
TI  - Spontaneous correction of dorsal intercalated segment instability deformity with
      scaphoid malunion in the skeletally immature.
AB  - This is a report on two children with dorsal intercalated segment instability
      deformity of the carpus associated with malunited fracture of the scaphoid. The
      patients were observed over 4 years, and spontaneous improvement was noted in
      association with growth.

PMID- 8294733
TI  - Alveolar soft-part sarcoma of the hand.

PMID- 8294734
TI  - Osteoid osteoma of the upper extremity.
AB  - Forty-six patients with histologically confirmed osteoid osteoma of the upper
      extremity seen from 1947 to 1990 were retrospectively reviewed. The patients' age
      at presentation averaged 20 years. Twenty-four of the lesions were located in the
      wrist and hand and 22 in the arm and forearm. The average duration of symptoms
      before diagnosis was 15 months. Pain was the presenting symptom in 44 of 46
      patients. Of the 28 patients who took aspirin for pain, 24 obtained at least
      partial relief. A mass or swelling was more commonly noted in lesions of the hand
      and wrist as compared to the arm and forearm. The diagnosis of osteoid osteoma
      was made by plain x-ray films alone in 35 cases. Bone scans were performed on 13
      patients; all were positive at the site of the lesion. Tomography was performed
      in 13 cases to identify the intraosseous location of the lesion. All lesions were
      treated by excision and curettage. Thirty-four of the 46 patients were followed
      at our institution for more than 6 months, with an average follow-up period of 27
      months. Six of the patients had persistent lesions. Of the six persistent osteoid
      osteomas, five occurred in the wrist or hand (p = .0012). A total of 15
      procedures were required to excise these lesions.

PMID- 8294735
TI  - Intraosseous glomus tumor of the phalanx: a case report.

PMID- 8294736
TI  - The natural history of a lipofibromatous hamartoma of the palm: a case report.

PMID- 8294737
TI  - Lipofibromatous hamartomas of the median nerve.
AB  - Five cases of lipofibromatous hamartoma of the median nerve are reported. The
      initial onset of symptoms and recognition of a mass occurred in adults in four
      cases. The fifth patient was an infant when the mass was first noticed, and she
      also had macrodactyly. Treatment included carpal tunnel release in three
      patients, one of whom required a second procedure for excision of the mass and
      sural nerve grafting. Nerve ablation without grafting was performed in the other
      two patients; one of these patients noticed no sensory or motor deficit after
      surgery. From this small series we cannot recommend a preferred treatment for
      these patients; each case must be approached on an individual basis. The
      diagnosis is best confirmed by biopsy.

PMID- 8294738
TI  - Injury to the deep motor branch of the ulnar nerve during carpal tunnel release.

PMID- 8294739
TI  - Carpal tunnel release without a tourniquet.
AB  - Release of the transverse carpal ligament can be performed safely under local
      anesthesia. The addition of epinephrine to the local anesthetic will cause
      sufficient vasoconstriction to maintain a dry field without the need of a
      tourniquet. This allows the procedure to be performed without regard to
      tourniquet pain. It has been our technique of choice in patients with functioning
      hemodialysis fistulae. The procedure was performed in 21 wrists to assess its
      safety. This approach was found to be a safe, effective, and efficient
      alternative to the standard tourniquet-dependent procedure.

PMID- 8294740
TI  - Rehabilitation of carpal tunnel surgery patients using a short surgical incision
      and an early program of physical therapy.
AB  - One goal of surgery for carpal tunnel syndrome is to return the patient to work
      or full-time activities in the shortest possible period of time. The authors
      evaluated the effectiveness of two incisions, a short incision less than 2.5 cm
      and an incision greater than 2.5 cm, both combined with a program of active
      postoperative hand-therapy in a group of 216 patients (293 release). When
      compared to other techniques with or without active physical therapy, our
      combined program achieved as short a median return-to-work interval as any other
      method, both for workers' compensation patients (21 days) and for
      private/Medicare/welfare patients (10 days). The operating time averaged 7
      minutes, and postoperative complications were few. The findings suggest that
      early hand therapy is more important than the short incision for minimizing the
      interval for regaining normal function and for decreasing the time-loss cost.

PMID- 8294741
TI  - Occupational exposure to hand vibration in northern Ontario gold miners.
AB  - Nineteen underground gold mine drillers who operate vibration equipment and a
      control group of 16 gold mill workers without vibration exposure were evaluated.
      Assessment included static two-point discrimination, moving two-point
      discrimination, vibration threshold, and cutaneous pressure threshold.
      Provocative tests, including Tinel, pressure, and Phalen signs, were performed at
      the carpal and cubital tunnels. Mean age of the miners was 35 years, and the mean
      age of the control group was 31 years. The mean time of vibration exposure was 14
      years. Numbness, pain, and weakness was reported in 12 miners and 1 control
      subject. Symptoms of vibration white finger were found in 16 miners and 3 control
      subjects. The miners had a higher incidence of positive provocative tests at the
      carpal and cubital tunnels and higher cutaneous pressure thresholds than the
      control group. Significantly higher vibration thresholds were found in the miners
      versus the control subjects. A correlation between years of vibration exposure
      and vibration threshold was found.

PMID- 8294742
TI  - Comparative fatigue strengths and stabilities of metacarpal internal fixation
      techniques.
AB  - To study quantitative differences in the fatigue strength and stability obtained
      with 5 types of internal fixation of metacarpal fractures, 105 preserved human
      metacarpals were cyclically tested in bending, torsion, and axial loading after
      oblique osteotomies of the metacarpal and internal fixation. The dorsal plate
      with lag screw was superior in all modes, followed by the two dorsal lag screws,
      crossed Kirschner wire tension banding, and intramedullary Kirschner wire
      fixation. The five intramedullary and the paired intramedullary Kirschner wire
      fixations were not statistically different. The fatigue life of the plate
      fixation was significantly larger in bending (1.5 times), torsion (1.6 times),
      and axial loading (2.5 times) than the second strongest fixation, two dorsal lag
      screws. Its initial rigidity was significantly higher in axial loading (1.5
      times) but was not statistically different in bending and torsion.

PMID- 8294743
TI  - Derotation osteotomy of the forearm in management of paralytic supination
      deformity.
AB  - Ten children with supination deformity of the forearm due to obstetric paralysis
      were treated by pronation osteotomy of the radius and ulna. In two patients
      release of the interosseous membrane was added. The main achievement of the
      operation was an improved position of rest, which rendered a mechanical advantage
      for the basic function of the hand in grasping medium-sized objects. Preliminary
      results of three other patients who recently underwent rerouting of the biceps
      tendon concurrently or following the osteotomy are encouraging. One patient who
      had both procedures underwent rerouting of the biceps, which resulted in a gain
      of 135 degrees of active pronation.

PMID- 8294744
TI  - Hook of hamate vascularity: vulnerability to osteonecrosis and nonunion.
AB  - A clinical impression of avascular changes in the hook of the hamate after
      fracture led to this study of the pattern and size of the hamate hook vascular
      foramina. It appears that vessels enter the hamate hook at primarily two sites.
      The radial base foramina are large and always present, while the ulnar tip
      foramina are small and absent in 29% of specimens. In these hamates, fracture at
      the hook base could potentially compromise blood supply to the hook fragment, and
      this may be a factor in hamate hook nonunion.

PMID- 8294745
TI  - Effects of antihistamines on joint stiffness and bone healing after periarticular
      fracture.
AB  - In an effort to blunt the inflammatory response following injury, we studied the
      effects of antihistamines on joint stiffness and bone healing after periarticular
      fracture. The hind limbs of 37 New Zealand white rabbits were instrumented with
      intramedullary Steinmann pins to allow immobilization after creating a distal
      tibia fracture. After periarticular ankle fracture, the rabbits were divided into
      groups to receive chlorpheniramine, low-dose terfenadine, high-dose terfenadine,
      or no antihistamine. Antihistamine was administered for the first 5 days after
      fracture. At 3 weeks after fracture, the rabbits treated with antihistamines
      showed a significant reduction in joint stiffness compared to control animals. To
      determine if antihistamine also retarded bone healing, an additional 12 New
      Zealand white rabbits underwent bilateral drilling of the midshaft of the femur
      with a 2.5 mm Steinmann pin. Six animals received oral terfenadine, and six
      served as controls. After 5 weeks of cage activity, the animals treated with the
      antihistamine showed a significant decrease in energy to failure of the femurs on
      torsional testing. Qualitative microscopic examination revealed less mature
      callus at the site of the femoral cortical defect in those animals treated with
      the terfenadine. Antihistamine may have heretofore unconsidered benefits in
      preventing post-traumatic joint stiffness but may slow healing of associated bony
      injuries.

PMID- 8294746
TI  - Osteochondral metatarsophalangeal autografts for traumatic articular
      metacarpophalangeal defects: a preliminary report.
AB  - Five consecutive patients with saw injuries to the dorsal portion of the index
      metacarpophalangeal joint and resultant partial osteochondral defects underwent
      articular reconstruction using contoured metatarsophalangeal osteochondral
      autografts. At an average follow-up period of 33 months, all patients achieved
      full metacarpophalangeal extension, with 74 degrees of flexion and grip strength
      equal to 86% of the contralateral hand. Discomfort was minimal, with crepitus
      present in one patient. X-ray films revealed joint space narrowing or articular
      step-off of 1 mm or less.

PMID- 8294747
TI  - Report of the 1992 Sterling Bunnell Traveling Fellow. Primary idiopathic
      osteoarthritis in the upper extremity.

PMID- 8294748
TI  - Scapholunate advanced collapse pattern of arthritis in calcium pyrophosphate
      deposition disease of the wrist.
AB  - Chondrocalcinosis is a well-described radiographic finding in patients with
      calcium pyrophosphate dihydrate deposition disease of the wrist and other joints.
      The medical records and x-ray films of 12 patients evaluated over an 18-month
      period for chondrocalcinosis of the wrist were examined for symptoms and physical
      and x-ray film findings. Thirteen wrists were affected. All wrists were noted to
      have calcification of the triangular fibrocartilage complex. Twelve of 13 wrists
      had the characteristic features of the scapholunate advanced collapse pattern of
      arthritis. In addition, there was a correlation in our series between
      chondrocalcinosis and carpal tunnel syndrome. Destruction of the interosseous
      soft tissues caused by crystalline deposition could alter the biomechanics of the
      wrist in a similar fashion to that of the post-traumatic scapholunate advanced
      collapse wrist leading to arthritic symptoms.

PMID- 8294749
TI  - Repair and/or reconstruction of scapholunate interosseous ligament in lunate and
      perilunate dislocations.
AB  - This study was undertaken to ascertain whether repair and/or reconstruction of
      the scapholunate interosseous ligament can prevent or reduce the occurrence of
      carpal instability and improve the clinical results. Thirty-two patients with
      lunate and perilunate dislocations were treated in the last 12 years. Of the 32,
      only 2 patients were seen within 4 weeks of injury, and the remaining 30 patients
      were seen and treated more than 4 weeks after the dislocation. Patients were
      followed for an average of 5 years. The scapholunate interosseous ligament was
      repaired and reconstructed in 12 patients (group 1). In 20 patients the ligament
      was not repaired or reconstructed (group 2). Clinical results were expressed by a
      modification of the point score method of Green and O'Brien. The scapholunate
      angles were measured on the lateral x-ray films with the wrist in neutral
      position. In group 1 clinical results averaged 82 points, while in group 2 they
      averaged 59 points. The scapholunate angles in group 1 averaged 50 degrees
      whereas in group 2 they averaged 69 degrees. These clinical and x-ray film
      results suggest that scapholunate interosseous ligament repair and/or
      reconstruction can prevent or reduce the occurrence of carpal instability and
      improve clinical results.

PMID- 8294750
TI  - Chronic lunotriquetral instability: diagnosis and treatment.
AB  - Fourteen patients with chronic lunotriquetral instability were evaluated. Forced
      wrist extension was the most common mechanism of injury. Fourteen patients
      underwent lunotriquetral arthrodesis. Arthrograms were positive in 9 of the 12
      performed. In three cases abnormalities not identified by arthrography were
      demonstrated by arthroscopy. The follow-up period averaged 27 months. X-ray films
      showed fusion in 12 cases. One pseudarthrosis was asymptomatic. A second
      pseudarthrosis required a rearthrodesis that became solid 8 weeks after surgery.
      One patient had persistent wrist pain. Wrist motion compared to the contralateral
      side averaged 85%, 88%, 83% and 80%, respectively, for flexion, extension, ulnar
      deviation, and radial deviation. Grip strength compared to the contralateral side
      averaged 93%. Lunotriquetral instability is a clinical diagnosis confirmed by
      arthrography or arthroscopy. Lunotriquetral fusion reliably relieves pain while
      maintaining functional wrist motion and grip strength. The long-term effects of
      lunotriquetral fusion on carpal kinematics and wrist function are unknown.

PMID- 8294751
TI  - Lunotriquetral arthrodesis.
AB  - Lunotriquetral arthrodesis has been recommended for the treatment of disabling
      pain at the lunotriquetral joint after more conservative measures have failed. We
      retrospectively analyzed a series of 22 patients treated with a lunotriquetral
      arthrodesis for presence of fusion, method of fixation, duration of
      immobilization, carpal alignment, pain relief, and ability to return to work.
      Fixation with a Herbert screw supplemented with a Kirschner wire (K-wire) was
      superior to fixation with K-wires alone. Immobilization longer than 6 weeks was
      superior to immobilization less than 6 weeks. Combined use of a Herbert screw
      supplemented with a K-wire and immobilization longer than 6 weeks resulted in
      union in all patients, even when performed for nonunion after a prior attempted
      arthrodesis. Pain was improved in all patients; all patients who previously were
      working returned to work. Routine posteroanterior and lateral x-ray films often
      failed to adequately profile the arthrodesis site. We recommend using a Herbert
      screw supplemented with a K-wire for lunotriquetral arthrodesis and keeping the
      patient in a cast until fusion is documented, usually at least 8 weeks.
      Fluoroscopic spot views or tomograms are recommended to demonstrate bone fusion.

PMID- 8294752
TI  - Complications of intercarpal arthrodesis.
AB  - Fifty patients who underwent intercarpal arthrodesis were retrospectively
      reviewed at an average follow-up period of 34 months. Eighteen patients had a
      good result, 16 results were fair, and 13 were poor. Thirty-six patients
      experienced some complication, and 25 patients underwent further surgical
      therapy: The most common indication for secondary surgery was nonunion (16
      patients). Good results were significantly decreased among patients who
      experienced nonunion, required secondary surgery, or experienced any
      complication. Patients with static carpal instability treated by scaphoid
      trapezoid trapezium arthrodesis had a significantly greater proportion of good
      results.

PMID- 8294753
TI  - Avascular necrosis of the capitate.

PMID- 8294754
TI  - Effects of the fasciocutaneous radial forearm flap on vascularity of the hand.
AB  - Twelve randomly selected fasciocutaneous radial forearm flaps underwent bilateral
      vascular analysis an average of 26 months following surgery. Digital temperature
      comparisons revealed an average 2.5% (0.8 degree C) decrease following use of the
      radial forearm flap. Doppler flow studies performed to determine the
      digital/brachial pressure indices revealed no significant difference between the
      donor (1.06) and control (1.08) extremities; however, Doppler pulse-volume
      recordings performed after cold stress testing revealed an 18% delay in
      reconstitution of normothermia in the radial forearm flap group compared to
      controls. Only two patients reported transient mild symptoms of cold intolerance,
      which resolved over time.

PMID- 8294755
TI  - Tubed radial fascial flap and reconstruction of the flexor apparatus in the
      forearm.
AB  - A reversed radial forearm fascial flap has been used as a vascularized tube
      through which tendon grafts may glide and in which nerve grafts may rest. It may
      have applications in the treatment of the severely damaged flexor system at wrist
      level. A further advantage of this technique is that it does not [corrected]
      sacrifice the radial artery in an already injured hand.

PMID- 8294756
TI  - Leukocyte-depleting effect of hypothermia on muscle flap microcirculation
      following ischemia-reperfusion injury.
AB  - The aim of this study was to determine the effect of leukocyte-endothelial
      interaction and capillary perfusion on the microcirculation of muscle flaps
      submitted to ischemia in normothermic and hypothermic conditions. The cremaster
      muscle flap model was employed. Sixty rats were studied in six groups:
      normothermic and hypothermic control groups and groups that underwent reperfusion
      after 4 and 6 hours of ischemia in both normothermic and hypothermic conditions.
      In each group the following measurements were made: main vessel diameters, red
      blood cell velocities, the number of perfused capillaries, and the number of
      leukocytes rolling and sticking in the postcapillary venules. Hypothermia
      decreased the flow rate significantly and eliminated leukocytes from the
      microcirculation. Six hours of ischemia under normothermic conditions proved to
      be lethal for these muscle flaps, whereas hypothermia preserved flap viability.

PMID- 8294757
TI  - Composite finger metacarpophalangeal joint reconstruction in combined second and
      third free toe-to-hand transfers.
AB  - Composite metacarpophalangeal joint reconstruction using the toe proximal phalanx
      and the metacarpal head, with a capsular repair, is an option during free toe
      transfer procedures for absent fingers. Eleven composite metacarpophalangeal
      finger joint reconstructions were performed in four patients concurrent with
      combined second and third toe-to-hand transfer. The average follow-up period was
      5 years. Postoperative assessment included range of motion, stability,
      radiographic changes, and pain. The average range of motion was 52 degrees,
      average ulnar stress deviation was 14 degrees. No patients complained of pain.
      Composite metacarpophalangeal joint reconstruction should be considered in free
      toe-to-hand procedures when metacarpal head articular cartilage is preserved.

PMID- 8294758
TI  - The Sauve-Kapandji procedure for reconstruction of the rheumatoid distal
      radioulnar joint.
AB  - Our experience with the Sauve-Kapandji procedure for reconstruction of the
      rheumatoid distal radioulnar joint is reported. Twenty-one wrists in 17 patients
      were followed for an average of 39 months postoperatively. Average range of
      motion at follow-up evaluation was pronation to 78 degrees and supination to 86
      degrees. X-ray films demonstrated that significant ulnarward and palmarward
      translocation of the carpus was prevented. The Sauve-Kapandji procedure provides
      a stable ulnar side support in the rheumatoid wrist with distal radioulnar
      degeneration.

PMID- 8294759
TI  - Soft tissue reconstruction for rheumatoid swan-neck and boutonniere deformities:
      long-term results.
AB  - Ninety-two fingers with rheumatoid swan-neck deformity were treated with dorsal
      capsulotomy and lateral band mobilization. An initial increase of 55 degrees of
      motion into flexion was noted, but this proximal interphalangeal motion
      deteriorated over time. Of 15 fingers followed at 3 and 12 months, there was a
      mean loss of 17 degrees of the early postoperative flexion. Nineteen fingers with
      rheumatoid boutonniere deformity were treated with central slip reconstruction.
      The results were unpredictable, with only modest improvement in the proximal
      interphalangeal extension, which deteriorated over time. The authors now
      recommend arthrodesis for most severe rheumatoid boutonniere deformities.

PMID- 8294760
TI  - Flexor pollicis longus rupture in rheumatoid arthritis secondary to attrition on
      a sesamoid.

PMID- 8294761
TI  - Rheumatoid lymphedema: a case report.

PMID- 8294762
TI  - Clinical features and treatment of congenital fusion of the small and ring finger
      metacarpals.
AB  - Nine cases of congenital fusion of the small and ring finger metacarpals are
      reported. The underlying etiology of congenital fusion of the small and ring
      finger metacarpals was ulnar ray deficiency in four hands, cleft hand in two
      hands, and symbrachydactyly in one hand; two hands were unclassifiable. X-ray
      films revealed that the small finger was hypoplastic and accompanied by
      brachymesophalangy in all cases. It was supposed that the main cause of
      congenital metacarpal fusion was the deficit of mesenchymal cells. Treatment for
      metacarpal fusion included splitting the metacarpal fusion and autogenous iliac
      bone graft in two hands, deepening of the interdigital space in two hands, and
      amputation of the small finger in one hand. Satisfactory improvement in
      appearance was achieved in three hands.

PMID- 8294763
TI  - [Application of PCR for isolation of Chlamydia pneumoniae].
AB  - Chlamydia pneumoniae was isolated from the throat swab of a 5-year-old girl with
      acute bronchitis. The titers of IgM and IgG antibodies to C. pneumoniae in the
      serum were 1:20 and 1:2560, respectively. C. pneumoniae genome was detected by
      polymerase chain reaction in the throat swab and the infected cells after three
      passages, while C. pneumoniae was isolated from the throat swab after five
      passages by cell culture. PCR is considered to be a helpful method to isolate C.
      pneumoniae efficiently in routine cell-cultures.

PMID- 8294764
TI  - [Studies on hemolytic streptococcal infection: 1). Outbreak of group C hemolytic
      streptococcal infection in Formosan squirrels].
AB  - Between mid-October to mid-November 1992, of 500 freely-ranging Formosan and
      striped squirrels kept at Garden Y in the suburbs of Kanagawa Prefecture, 414
      (82.8%) suddenly died one after another by bleeding from the nasal and oral
      cavities after developing a mild facial swelling. Isolation of microbes including
      viruses were carried out from the Formosan squirrels that had suddenly died.
      Various organs from these animals were histologically examined. 1. In
      bacteriological tests, beta-hemolytic streptococcal strains were isolated in a
      pure culture from 5 (83.3%) of 6 Formosan squirrels that had died suddenly. By
      serological analysis, 14 isolated strains were serotyped as group C according to
      the classification of Lancefield. From their biochemical characteristics, these
      were identified as Streptococcus equi subsp. zooepidemicus. A drug sensitivity
      test revealed that ABPC, PCG, SBPC, CMX and CPZ are highly sensitive against the
      isolates. 2. In the virological test, the viral isolation was applied for three
      blind passages by primary cultured kidney cells of Formosan squirrels, but no
      evidence of CPE was obtained. 3. At autopsy, a pathological change was detected
      mainly in the lungs. Histopathological examinations revealed severe hypertrophic
      changes of the alveolar wall in the entire pulmonary lobe. Severe congestion,
      hemorrhagic pneumonia, neutrophils and macrophages infiltration were observed in
      the hypertrophic alveolar wall. In the other cases, thrombi were observed in the
      branches of the pulmonary artery. Other organs demonstrated no remarkable
      histopathological changes. 4. Streptococcal strains were not isolated from the
      pharynx in all of the employees working at this garden.

PMID- 8294765
TI  - [A human monoclonal antibody cocktail for experimental mouse infection with
      clinically isolated strains of Pseudomonas aeruginosa].
AB  - A human IgG monoclonal antibody cocktail against Pseudomonas aeruginosa serotypes
      A, B, E, G, I, and M (MCA5) was tested for its therapeutic effect on the infected
      mice with clinically isolated P. aeruginosa strains. More than 80% of the
      collected strains were found to belong to the above six serotypes. Direct
      agglutination with MCA5 gave slight reduced rates, but over 70% of the strains
      were agglutinated with MCA5. Fifty percent lethal doses of the representative
      strains to mice (LD50) were estimated, and 50% protective doses of MCA5 to the
      infected mice with 5 LD50 of the strains (ED50) were determined. MCA5 was found
      not to be protective to all the infected mice with above six serotypes but
      protective only to the mice infected with the agglutinated strains. Confirmation
      of the agglutination of the causative organism with MCA5 is required for the
      treatment by MCA5. ED50 for a clinically isolated strain and the virulent stock
      strain were determined under the various challenge doses. It was found that ED50
      increased in parallel with the increase of challenged doses but did not change
      depending on the virulence of the infected strains. These results indicated that
      this cocktail worked as opsonin. Opsogenic anti-O IgG antibody could be most
      effective to protect the opportunistic infections caused by the bacteria which
      have not so powerful exotoxins.

PMID- 8294766
TI  - [Purple urine bag syndrome (PUBS) associated with strong alkaline urine].
AB  - Mechanisms for purple discoloration of the plastic urine bag in purple urine bag
      syndrome (PUBS) were investigated. Activities of bacterial indoxyl sulfatase
      catalyzing the conversion of indoxyl sulfate to indigo (or indirubin) were
      detected in strong alkaline liquid media but not in normal ones. These enzyme
      activities were particularly high in simple and combined cultures of Proteus
      mirabilis and/or Klebsiella pneumoniae. These results suggest that occurrence of
      PUBS is associated with strong alkaline urine as well as urinary tract infections
      induced by some species of bacteria with indoxyl sulfatase.

PMID- 8294767
TI  - Effect of recombinant human interleukin-2 on the chemotaxis and chemiluminescence
      of human polymorphonuclear leukocytes.
AB  - Recently, unusual frequency of bacteremia and neutrophil dysfunction during
      interleukin-2 (IL-2) therapy for advanced cancer has been reported. To determine
      the cause of this dysfunction, we investigated the effects of recombinant human
      IL-2 on the chemotaxis and chemiluminescence (CL) response of human
      polymorphonuclear leukocytes (PMNs) and the effects of tumor necrosis factor
      alpha (TNF-alpha), which is elevated after IL-2 administration, on the chemotaxis
      of human PMNs in vitro. After incubation of various concentrations of IL-2 or TNF
      alpha with PMNs obtained from healthy adults, the chemotactic response to
      stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine was measured by a
      modified Boyden chamber method. The CL response of PMNs and whole blood was
      measured by stimulation with non-opsonized zymosan, Staphylococcus aureus or
      phorbol myristate acetate after 10-minute incubation with IL-2. PMN chemotaxis
      (IL-2 concentration: 1, 10, 100, 1000 U/ml) and the CL response of PMNs and whole
      blood (IL-2 concentration: 1, 10, 100 U/ml) were unchanged when compared with the
      responses of untreated cells. However, PMN chemotaxis was significantly inhibited
      after incubation with TNF-alpha at concentrations of 1, 10 and 100 U/ml. These
      results demonstrate that IL-2 has no direct effect on PMN function; however, TNF
      alpha which increases in concentration following IL-2 therapy inhibits PMN
      chemotaxis, indicating that this factor may be a cause of chemotactic defects in
      PMNs during IL-2 therapy.

PMID- 8294768
TI  - [On the outbreak of Shigellosis in Tokyo, 1992].
AB  - In 1992, the number of cases of shigellosis in Tokyo increased remarkably, and a
      total of 10 separate outbreaks were confirmed. Except for 1 series where the
      causative strains was Shigella flexneri 3a, the other 9 outbreaks were caused by
      Shigella sonnei. Of note, 7 outbreaks were familial with less than 5 patients.
      The remaining 3 outbreaks occurred in a restaurant, a school and the dormitory of
      an orphanage, in which the organism was detected in 6 to 14 patients. In 4 of the
      familial outbreaks occurring in distant areas during August, ark shell was
      presumed to be the vehicle by epidemiological investigations and laboratory
      examinations. Analysis of isolates such as the antibiotic resistance pattern,
      plasmid profile, or colicine type in Shigella sonnei was useful in clarifying the
      commonality of each case and identifying the vehicle or transmission.

PMID- 8294769
TI  - [A study of respiratory infection and sepsis caused by MRSA at Hokusho Central
      Hospital].
AB  - At Hokusho Central Hospital, we studied the isolation rate of methicillin
      resistant Staphylococcus aureus (MRSA) from 1985 to 1989; respiratory infection
      with MRSA, in 1989; and sepsis of MRSA, from 1988 to 1989. The isolation rate of
      MRSA from sputum increased from 0% in 1985 to 65.4% in 1989. MRSA was isolated
      mainly from elderly patients in a geriatric ward, with 55 of 67 strains (82%)
      being isolated from these patients in 1989. MIC80 of isolated MRSA strains was
      0.01 microgram/ml to rifampicin, 0.02 microgram/ml to mynomycine, 3.13
      micrograms/ml to vancomycin, 12.5 micrograms/ml to ofloxacin and 100
      micrograms/ml to imipenem in 1989. One-third of the 60 isolated cases showed
      respiratory infections including 10 cases of pneumonia and 10 sepsis patients and
      11 blood samples in 1988 and 1989, especially 92.9% of S. aureus isolated in 1989
      was MRSA. Four of the 6 patients with respiratory infections of MRSA and 1 of the
      3 patients with MRSA sepsis were treated successfully by a combination therapy of
      imipenem/cilastatin and cefazolin.

PMID- 8294770
TI  - [Protective effect of a human immunoglobulin preparation on mouse experimental
      infection of methicillin resistant Staphylococcus aureus].
AB  - Methicillin resistant Staphylococcus aureus (MRSA) selectively increased by
      extensive chemotherapy is now one of the major causative agents of opportunistic
      infections in immunocompromised patients. Immunotherapy should be applied because
      this infection is based on the immunocompromised state of the patients. But this
      therapy has not been applied because S. aureus is known to have protein A which
      binds to the Fc portion of IgG and blocks phagocytosis through Fc receptor of
      phagocytic cells which plays the major role for the killing of infected bacteria
      in vivo. It should be known that MRSA strains often did not express protein A.
      Recently isolated MRSA strains were collected from three medical institutions and
      examined for their expression of protein A. Incidences of protein A-negative
      strains were different among institutions. It was found that more than a half of
      the strains from a general hospital which expressed typical heat sensitive
      methicillin resistance did not express protein A, but that incidences of protein
      A-negative strains were around 20% in the MRSA strains of a complicated history
      from a university hospital and a research center. All protein A-negative strains
      were found to be agglutinated by a commercially available immunoglobulin
      preparation (Venilon). And this immunoglobulin was proved to have a protective
      effect for the mouse experimental infections of these protein A-negative MRSA
      strains.

PMID- 8294771
TI  - [Study on mec gene in methicillin-resistant staphylococci].
AB  - Methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible
      Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus epidermidis
      and methicillin-resistant Staphylococcus haemolyticus strains which were isolated
      in 1992 were surveyed for distribution of mecA, mecR1 (putative mecA gene inducer
      gene) and mecI gene (putative mecA gene repressor gene) by the method of
      polymerase chain reaction (PCR). All the 30 strains (100%) of MRSA carried mecA
      gene and mecR1 gene-1 (32-357 bp, closer to mecA gene). In contrast, mecI gene
      (putative mecA gene repressor gene) and mecR1 gene-2 (987-1221 bp, closer to mecI
      gene) were detected in only 23 (73%) of the MRSA strains. By RT-PCR, the mecI
      gene existing in these highly resistant MRSA strains was demonstrated to remain
      inactivated. In 28 strains of MSSA and two strains of methicillin with MIC of
      6.25 micrograms/ml, all of the mec genes (mecA, mecR1 and mecI) were not
      detected. In contrast, in the other three strains, which were sensitive to
      methicillin in spite of the presence of mecA gene and defined as MSSA, the mec
      genes other than mecA were detected except for one strain. Methicillin-resistant
      (with MIC of 12.5 micrograms/ml or more) coagulase-negative staphylococci (15 S.
      epidermidis and 9 S. haemolyticus) strains were surveyed as well. As results, all
      the mec genes mentioned above were detected in all the strains except for one of
      S. epidermidis, but only mecA gene in the strains of S. haemolyticus. Thus, it
      was found that the composition of the mec genes of methicillin-resistant S.
      haemolyticus were more variant from that of methicillin-resistant strains of S.
      aureus and S. epidermidis.

PMID- 8294772
TI  - [A healthy carrier of verotoxin-producing Escherichia coli, who was detected by
      periodic feces examinations].
AB  - Verotoxin-producing Escherichia coli (VTEC) was rapidly detected by the PCR
      method in one of the 9 feces samples. They were collected from the people who had
      been cooking meals for patients on a periodic feces examination on November 25,
      1992. It was confirmed by PCR that the isolate had both VT1 and VT2vh toxic genes
      and showed cytotoxicity on Verocells. In this case, the isolate was highly
      susceptible to common antibiotic agents, it was removed by the administration of
      tosfulaxacin. Some isolates which had the same properties as those of the strain
      described in "VITEK GNI card" and the antimicrobial susceptibility and VT toxin
      types, were detected in 2 of the 3 members of her family, they were healthy
      carriers and did not have any subjective symptoms such as diarrhea or abdominal
      pain. In order to detect Verotoxic genes, the sample of feces preincubated for 3
      h in trypticase broth was subjected to PCR. We recommend that this method is much
      more useful because of rapid detection and identification of VTEC compared with
      the classical culture method.

PMID- 8294773
TI  - [Fulminant streptococcal infection and sudden death in a pregnant woman: a case
      report].
AB  - A case of fulminant streptococcal infection occurring in a 28-year-old pregnant
      female is reported. She initially developed pharyngitis and high fever during the
      33rd week of gestation. This was treated with oral piperacillin for two days with
      temporary amelioration. Recurrence of high fever, however, was noted shortly
      thereafter, which was followed by stillbirth of twin babies, and subsequent
      development of refractory hypotension and demise of the mother. Autopsy revealed
      presence of numerous cocci and fibrin thrombi in systemic circulation, and this
      was thought to be the immediate cause of her death. The causative organism was
      identified as Streptococcus pyogenes, M3, T3, and was found to be producing
      streptococcal pyrogenic exotoxin A in vitro. The underlying mechanism for this
      serious infection remains unknown.

PMID- 8294774
TI  - [Two cases of acquired immunodeficiency syndrome with disseminated non
      tuberculous mycobacterial infection].
AB  - Two cases of Acquired Immune Deficiency Syndrome (AIDS) with disseminated non
      tuberculous mycobacterial infection are reported. Both patients had hemophilia
      and were infected with Human Immunodeficiency Virus type 1 (HIV) by
      antihemophilic factor infusion. In case 1, a 44-year-old male, Mycobacterium
      marinum, which ordinarily causes cutaneous infection, was isolated from sputum
      before death and from the lung, spleen, bone marrow, liver and lymph node at
      autopsy. This is the first report of disseminated M. marinum infection with AIDS.
      In case 2, a 25-year-old male, Mycobacterium avium complex, which is the most
      common strain in non-tuberculous mycobacterial infection among patients with HIV,
      was isolated from the lung by TBLB and at autopsy from the lung, liver, spleen,
      bone marrow, lymph node, stomach, small intestine and testis. He also had a giant
      intraabdominal lymphadenopathy, associated with the M. avium complex
      infiltration. In conclusion, non-tuberculous mycobacteria can be easily
      disseminated in patients with AIDS because of dysfunction of cellular immunity,
      even when their primary lesions are not severe.

PMID- 8294775
TI  - [Five cases of respiratory infection due to Pasteurella multocida].
AB  - Five cases of respiratory infection in which Pasteurella multocida (P. multocida)
      was isolated from sputum were reported. All of the five patients had animal
      contact, and three of the five patients suffered from bronchiectasis. No
      underlying pulmonary disease was found in one case, P. multocida was also
      isolated from her cat. Patients were treated with ST, MINO + PIPC, ABPC + CFT,
      SBTPC, AMK + MINO with improvement. Thirty cases of respiratory tract infection
      due to P. multocida including our cases have been reported in Japan.

PMID- 8294776
TI  - [Antibody titers of an human immunoglobulin preparation against group B
      streptococci].

PMID- 8294777
TI  - [Protein C anticoagulant pathway and its abnormality].

PMID- 8294778
TI  - [The signal transduction mediated by the products of rel-related genes].

PMID- 8294779
TI  - [Cell cycle-dependent nuclear transport of v-Jun].

PMID- 8294780
TI  - [A new member of the insulin receptor family, insulin receptor-related receptor].

PMID- 8294781
TI  - [Proteinases in ovarian follicular maturation].

PMID- 8294782
TI  - [What does sperm recognize on fusing cells?].

PMID- 8294783
TI  - [Structural aspects of fusion machinery].

PMID- 8294784
TI  - [Clinical aspects of calcium metabolism disorders of the bone. I. Basic topics.
      1. Hormones regulating bone calcium metabolism].

PMID- 8294785
TI  - [Clinical aspects of calcium metabolism disorders of the bone. I. Basic topics.
      2. Screening of primary hyperparathyroidism].

PMID- 8294786
TI  - [Clinical aspects of calcium metabolism disorders of the bone. I. Basic topics.
      3. Differential diagnosis of hypercalciuria].

PMID- 8294787
TI  - [Clinical aspects of calcium metabolism disorders of the bone. I. Basic topics.
      4. Vitamin D metabolism disorders].

PMID- 8294788
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 1. Hypercalcemia: 1) Differential diagnosis].

PMID- 8294789
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 1. Hypercalcemia: 2) Primary hyperparathyroidism].

PMID- 8294790
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 1. Hypercalcemia: 3) Sarcoidosis, granulomatous
      diseases, and hypercalcemia].

PMID- 8294791
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 1. Hypercalcemia: 4) Familial hypocalciuric
      hypercalcemia].

PMID- 8294792
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 2. Hypocalcemia: 1) Idiopathic hypoparathyroidism].

PMID- 8294793
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 2. Hypocalcemia: 1) Pseudo- and
      pseudopseudohypoparathyroidism].

PMID- 8294794
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 2. Hypocalcemia: 3) Abnormal Ca metabolism in chronic
      renal failure].

PMID- 8294795
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 3. Metabolic diseases of the bone: 1) Concept and
      classification of osteoporosis].

PMID- 8294796
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 3. Bone metabolism disorders: 2) Markers of bone
      metabolism and diagnosis of osteoporosis].

PMID- 8294797
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 3. Metabolic diseases of the bone: 3) Current status and
      problems of quantitative analysis of bone minerals].

PMID- 8294798
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 2. Metabolic diseases of the bone: 4) Prevention and
      treatment of osteoporosis].

PMID- 8294799
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 3. Bone metabolism diseases: 5) Renal osteodystrophy].

PMID- 8294800
TI  - [Clinical aspects of calcium metabolism disorders of the bone. II. Progress in
      diagnosis and treatment. 3. Bone metabolism disorders: 6) Clinical description of
      rickets and osteomalacia].

PMID- 8294801
TI  - [Clinical aspects of calcium metabolism disorders of the bone. III. Current
      topics. 1. Hypercalcemia associated with malignant tumor and PTHRP].

PMID- 8294802
TI  - [Clinical aspects of calcium metabolism disorders of the bone. III. Current
      topics. 2. Hypercalcemia associated with malignant tumor: progress in the
      treatment].

PMID- 8294804
TI  - [Abnormal calcium-bone metabolism: current topics].

PMID- 8294803
TI  - [Clinical aspects of calcium metabolism disorders of the bone. III. Current
      topics. 3. Structures and functions of PTH- and calcitonin- receptors].

PMID- 8294805
TI  - [Case of active infectious endocarditis taking a rapidly changing clinical course
      and exhibiting accentuated atrioventricular block and perforation of the right
      Valsalva's sinus].

PMID- 8294806
TI  - [Case of intramuscular nodular sarcoidosis].

PMID- 8294807
TI  - [Case of secondary carnitine deficiency (in a patient undergoing hemodialysis),
      developing rhabdomyolysis due to dehydration and the action of a hypolipemic
      agent].

PMID- 8294808
TI  - [Case of Japanese encephalitis exhibiting a unique MRI characteristics shortly
      after onset].

PMID- 8294809
TI  - [Case of infectious mononucleosis-like syndrome suspected to be due to Coxsackie
      B4 virus infection].

PMID- 8294810
TI  - [Diabetes mellitus and bone marrow transplantation].

PMID- 8294811
TI  - [Glucose transporters--their abnormalities and significance in disease states].

PMID- 8294812
TI  - Arterial spasticity and cold intolerance in relation to time after digital
      replantation.
AB  - Cold induced arterial vasospasm was studied in ten patients with single digit
      replantation, by measuring finger systolic pressure at different finger
      temperatures. Each patient was examined three times; within 2 weeks of surgery,
      after 1 year and after 3 years. The replantations were performed using long
      arterial and venous grafts. Cold-related vasospasm is established during the
      first year after trauma, and thereafter seems to be persistent. It is concluded
      that the subjective cold tolerance, which affects all patients after digital
      amputation regardless of whether replantation is performed or not, is partly due
      to vasospasm. It is less pronounced in patients without pathological vasospasm in
      the replanted digit. Cold intolerance is likely to decrease during the first 2
      years after replantation, but not to disappear completely.

PMID- 8294813
TI  - The functional results of hand replantation. The Chepstow experience.
AB  - Eight hands amputated at wrist or distal forearm level were replanted between
      1983 and 1990. Steinman pins were used to obtain skeletal fixation at the wrist
      level in three patients. Secondary surgery was performed in seven patients. Six
      of the patients were available for review between 1.5 and 7.5 years (mean 3.6)
      after the injury. The functional results were assessed using the Tamai scoring
      system. Recovery of useful hand function has been achieved in most patients,
      although long-term recovery of sensibility was found to be disappointing. Despite
      this finding, five out of the six patients were highly satisfied with the result
      and four have returned to work.

PMID- 8294814
TI  - Bone reconstruction with a free vascularized fibular graft after giant cell
      tumour resection.
AB  - Free vascularized fibular transfers were used in six patients with extensive bony
      defects after excision of a giant cell tumour of the distal end of the radius.
      The results have been satisfactory.

PMID- 8294815
TI  - Primary extensor tendon reconstruction in dorsal hand defects requiring free
      flaps.
AB  - This study reports results in nine patients with extensive loss of soft tissue,
      extensor tendon, and bone, treated with an emergency free flap for skin cover,
      primary bone grafts, and tendon grafts passed through individual tunnels in the
      free flap. Four had a good result, four were fair and one poor. Six patients
      returned to work, two were not working and one was retired. In select patients,
      emergency reconstruction of severe extensor tendon injuries appears to produce
      better function, with fewer operations, a shorter hospital stay, minimal
      complications, and a shorter period of disability.

PMID- 8294816
TI  - Pronator quadratus free muscle flap for treatment of palmar defects.
AB  - Cutaneous flaps are not entirely satisfactory when used for soft tissue defects
      of the palm, because the skin cover is too mobile. Use of muscle flaps can
      therefore be advocated for this recipient site. A case is reported where the
      pronator quadratus muscle has been used as a free muscle flap for coverage of a
      small defect of the palm.

PMID- 8294818
TI  - Harvest of palmaris longus tendon: technique.
AB  - We present a modification of Bunnell's technique for harvest of the palmaris
      longus tendon. Using a 0.5 cm distal incision and a proximal stab incision the
      tendon is harvested with minimal scarring and, in our experience of over 30
      cases, no morbidity.

PMID- 8294817
TI  - Bilateral extensor medii digiti: a rare anatomical variation.
AB  - A supernumerary extensor muscle to the middle finger was found to be present
      bilaterally in a male cadaver. It originated from the distal end of the ulna and
      its tendon inserted into the proximal phalanx of the middle finger. The bilateral
      presence and manner of insertion appear to be unique from a review of the
      literature. Morphological variability and clinical significance are reviewed.
      Such variations may be clinically significant during hand surgery, especially
      tendon transfer procedures.

PMID- 8294819
TI  - Attrition rupture of flexor tendons at the wrist following epiphyseal fracture of
      the distal radius.
AB  - Post-traumatic rupture of flexor tendons is a very rare event. We report such an
      event following an epiphyseal fracture of the distal radius. This has not
      previously been reported in the English literature.

PMID- 8294820
TI  - Poor correlation between functional results and radiographic findings in Colles'
      fracture.
AB  - We reviewed 83 consecutive patients with unilateral Colles' fracture in order to
      identify factors that predict poor functional outcome. All fractures were treated
      by closed reduction and cast immobilization, and followed-up for at least 2
      years. Our results showed that only final dorsal angulation was correlated to
      loss of flexion. In contrast to other reports, we could not find any relationship
      between radial shortening and loss of grip strength or loss of range of motion.
      In addition, the severity of initial displacement, involvement of radio-carpal or
      distal radio-ulnar joints, and the presence of ulnar styloid fractures or their
      non-union did not affect the functional outcome.

PMID- 8294821
TI  - Radio-ulnar synostosis following external fixation.
AB  - Post-traumatic radio-ulnar synostosis is an unusual but serious complication of
      adult forearm fractures. This is the first report of radio-ulnar synostosis
      following external fixation to be described in the English literature. A 52-year
      old man sustained a fracture of the distal radius and ulna which was managed by
      external fixation. Following this, he developed a radio-ulnar synostosis at the
      pin-track site. The synostosis was successfully removed and he regained
      significant rotatory movement of his forearm.

PMID- 8294822
TI  - Wrist arthrodesis using an embedded iliac crest bone graft.
AB  - 34 patients treated by the iliac crest bone graft technique for wrist arthrodesis
      were reviewed. The average age was 45.6 years and the mean follow-up was 45
      months. The procedure is performed through a straight ulnar approach and the head
      of the ulna is removed. A longitudinal trench is created in both distal radius
      and carpus preserving the anterior, posterior and lateral cortices. A curved
      trapezoidal monocortical iliac crest bone graft is embedded inside the trench.
      The position of the arthrodesis automatically follows the curvature of the graft.
      No fixation device is used. A short-arm cast is applied for 2 to 3 months. All
      arthrodeses except two fused within 3 months. Pain was completely relieved in 85%
      of the cases. Pronation and supination returned to normal 5 months post
      operatively. Grip strength was increased in 80% of the cases. The carpometacarpal
      joints remained pain-free even when not fused. Complications were rare: two
      lesions of the dorsal branch of the ulnar nerve; two cases of delayed union due
      to errors in technique, and displacement of the graft in one case. Although it is
      technically demanding, the embedded iliac crest graft wrist arthrodesis improves
      pronation and supination as a result of resection of the distal radio-ulnar
      joint, preserves or improves grip strength, and relieves pain.

PMID- 8294823
TI  - Madelung's deformity. A surgical technique.
AB  - 15 wrists with Madelung's deformity were operated on between 1972 and 1990,
      constituting the largest series of radial osteotomies reported for this deformity
      to date. The technique that evolved is described in detail, as are the
      preliminary follow-up results. All patients reported symptomatic relief and
      return to normal activity levels.

PMID- 8294824
TI  - Excision of the hamate for an unusual hand tumour.
AB  - A right-handed man with an enlarging bony swelling of his dominant hand developed
      symptoms of median and ulnar nerve compression. He underwent simple excision of
      the hamate and histology showed the lesion to be a benign chondroblastoma. At 2
      year follow-up he was found to be doing a heavy manual job with no functional
      problems and there were no signs of recurrence of the tumour. To our knowledge
      this is the first reported case of a benign hand tumour treated by simple
      excision of the hamate.

PMID- 8294825
TI  - Kinematic analysis of relative motion within the proximal carpal row.
AB  - The motions of the scaphoid and triquetrum relative to the lunate have been
      studied on cadaver specimens. The helical axis concept was applied. The wrist
      motions performed were flexion-extension and radial-ulnar deviation. The results
      showed increased relative motion of the scaphoid towards terminal extension, and
      to a lesser amount in the case of the triquetrum, towards terminal flexion. The
      lunate might be considered as a keystone in the proximal carpal row when wrist
      stability is considered. It is doubly intercalated: longitudinally and
      transversely. Wrist ligaments co-ordinate the positioning of the bones in the mid
      range of carpal motions, and restrict further motion in extreme positions of the
      wrist joint.

PMID- 8294826
TI  - Resection arthroplasty of the proximal interphalangeal joint.
AB  - Palmar plate resection arthroplasty of the PIP joint, a new technique for
      operative treatment of destroyed PIP joints, is presented. By combining palmar
      plate arthroplasty with a flexor tenodesis a stable arthroplasty with adequate
      active motion can be performed. It can be used even in severely destroyed joints
      and still provide adequate post-operative stability and motion. Exercise can be
      started early.

PMID- 8294827
TI  - Trapeziectomy and ligament reconstruction for osteoarthrosis of the base of the
      thumb. A prospective study of 100 operations.
AB  - 100 thumbs with primary osteoarthrosis of the joints of the trapezium were
      treated by trapeziectomy and a FCR sling arthroplasty to reconstruct a first
      intermetacarpal ligament by the method described by Burton and Pellegrini (1986).
      Pain at rest remained in five. Some pain at or after exertion persisted in 46,
      and 49 became completely pain-free. 88 were satisfied with the procedure and
      there was a significant increase in pinch strength and in the ability to perform
      activities of daily life. It has become our preferred procedure for treating
      osteoarthrosis of the basal joint of the thumb.

PMID- 8294828
TI  - Changes in carpal tunnel shape during wrist joint motion. MRI evaluation of
      normal volunteers.
AB  - This study evaluated dynamically the morphology of the carpal tunnel during the
      wrist motion. The object was to determine the transverse dimension (TD),
      anteroposterior (AP) dimension and cross-sectional area (CA) of the carpal tunnel
      in the neutral, flexed and extended positions. The wrists of eight male and eight
      female volunteers aged 20 to 38 years were studied. With wrist extension, AP and
      CA decreased while the TD increased at the pisiform level, and CA increased at
      the hamate level. With flexion, TD and CA decreased at the pisiform level and CA
      decreased at the hamate level. The results showed that the median nerve may be
      subjected to significant pressure at the pisiform level when the wrist is
      extended. During wrist flexion, the cross-sectional area decreased at both the
      level of the pisiform and the hook of the hamate.

PMID- 8294829
TI  - Measuring outcome in median nerve injuries.
AB  - Assessing the functional outcome of peripheral nerve suture in the hand requires
      a battery of tests which are valid, reliable and comprehensively evaluate
      cutaneous sensibility. This study explores the relationship between a battery of
      sensory tests and the patient's capacity to perform everyday functional
      activities. An analysis of the interrelationship between all outcome variables
      reveals that the tests of sensibility do not predict the patients' ability to use
      their hands in everyday activities, thus indicating that patients are able to
      compensate for sensory deficit through the use of vision and bilateral use of the
      hands. An assessment of outcome should therefore include an additional measure of
      performance on daily living tasks.

PMID- 8294830
TI  - Can a divided digital nerve on one side of the finger be left unrepaired?
AB  - 72 fingers with divided digital nerves on one side alone had their nerves
      repaired and the sensory recovery assessed at different intervals of up to 2
      years. Another 36 fingers with similar digital nerve injuries had their divided
      nerves left unrepaired and sensory recovery similarly assessed for comparison. In
      the "repaired" group, the result continued to improve and by 2 years, 90% reached
      S3+ or above. In the "unrepaired" group, improvement plateaued after 6 months,
      and at 2 years only 6% reached S3+ or above, although all had regained some
      protective sensibility.

PMID- 8294831
TI  - Finger dynamography. A complimentary technique for functional evaluation of the
      hand.
AB  - The movements of the MP and PIP joints occur together and enable the fingers to
      acquire different postures. A graphic record of these movements gives an idea of
      the working space of the fingers. Normally, the tracing forms the shape of a
      quadrangle with almost parallel sides. If muscle paralysis occurs or joints are
      diseased, the shape of the quadrangle--the "working space"--becomes distorted.
      Different patterns of distortion are seen with different finger problems. "Finger
      dynamography" is a simple bedside procedure requiring only a goniometer. If
      supplemented with additional data on pinch and grip strengths and sensibility, it
      gives a pictorial record which is easy to interpret and can be used for
      documentation.

PMID- 8294832
TI  - Evaluation of methods of claw finger correction using the finger dynamography
      technique.
AB  - Finger dynamography is a bedside technique for evaluation of the moving abilities
      and working space of the hand. Various operative procedures used for correcting
      the claw finger deformity restore the functional abilities to a varying extent.
      The palmaris longus transfer with insertion into A1-A2 pulley appears to be a
      better procedure than lateral band insertion, extensor diversion or extensor many
      tail procedures. The use of palmaris longus as a motor seems to have advantages
      over flexor digitorum superficialis transfer where removal of FDS as a motor
      produces local deficits.

PMID- 8294833
TI  - A comparison of upper arm and forearm tourniquet tolerance.
AB  - This study examined the use of upper arm and forearm tourniquets for hand
      surgery. 40 subjects (20 males, 20 females) were randomly assigned to one of four
      groups: left upper arm, left forearm, right upper arm and right forearm.
      Tourniquets were applied to these areas. Subjects were asked to rate their
      discomfort at 10-minute intervals and the total time of tourniquet tolerance was
      recorded. The results of a three-factor ANOVA revealed no statistically
      significant differences in either pain rating or tourniquet tolerance between any
      of the groups. In addition, forearm tourniquets were used in 18 clinical cases.
      None of the individuals with tourniquet times less than 30 minutes required any
      medication in order to tolerate this procedure. Of the 13 patients with
      tourniquet times greater than 30 minutes, ten required medication in order to
      tolerate the procedure. We conclude that patients tolerate upper arm and forearm
      tourniquets equally.

PMID- 8294834
TI  - Injuries to the hand and wrist. A study of 50,272 injuries.
AB  - This study reports the causes, characteristics and treatment of injuries to the
      hand and wrist presented to five accident and emergency departments in a 2-year
      survey of 13% of the Danish population. The rate of injury to the hand or wrist
      was 28.6% of all injuries, or 3.7 per 100,000 inhabitants per year. 34% of the
      accidents were domestic, 35% were leisure accidents, 26% were occupational and 5%
      were traffic accidents. Only 2% of the patients were admitted to hospital for
      further treatment or observation and 13% were referred to a hospital as
      outpatients. The most frequent causes for admission were fractures (42%), tendon
      lesions (29%) and wounds (12%).

PMID- 8294835
TI  - Diagnosis of the aetiology of a locked metacarpophalangeal joint using MRI.
AB  - A case is reported of a locked MP joint due to ulceration of the metacarpal head.
      This was clearly visible on MRI scan.

PMID- 8294836
TI  - Irreducible rotational anterior dislocation of the proximal interphalangeal
      joint. A spin drier injury.
AB  - Two cases are described of anterior dislocation of the proximal interphalangeal
      joint which could not be reduced because of interposition of the central slip of
      the extensor mechanism. In common with previously reported cases the injuries
      were sustained in a spin drier. The literature on anterior dislocation of the
      proximal interphalangeal joint is reviewed. Three distinct patterns of
      dislocation are recognised and their management is discussed.

PMID- 8294837
TI  - Nail gun injuries of the fingers: a safer method of nail removal.
AB  - In nail gun injuries of the fingers, removal of the nail in the antegrade fashion
      (in the same direction as its introduction) prevents soft tissue entrapment by
      the hooked barbs of the nail. This concept is illustrated in a case report.

PMID- 8294838
TI  - Accidental injection of white spirit into the hand in golfers.
AB  - We report two cases in which white spirit has been injected accidentally into the
      hand by golfers, while attempting to remove the grip of the golf-club handle in
      order to replace it. One of our patients has anecdotal evidence of this happening
      in at least two other cases, one of which resulted in amputation of the index
      finger, and the other in severe damage to the thumb.

PMID- 8294839
TI  - The presence of myofibroblasts in the dermis of patients with Dupuytren's
      contracture. A possible source for recurrence.
AB  - Samples of skin and underlying cord obtained at dermofasciectomy for Dupuytren's
      contracture have been examined for the presence of smooth muscle alpha-actin (SM
      alpha-actin), a marker for myofibroblasts. 15 of the 20 samples stained
      positively for SM alpha-actin corresponding with areas of hypercellular
      Dupuytren's tissue. In 12 of these 15 samples SM alpha-actin-positive
      hypercellular Dupuytren's tissue extended into the dermis, in three cases
      reaching the epidermis. In eight samples, diffusely distributed cells positive
      for SM alpha-actin and resembling fibroblasts were seen in the dermis. These
      cells appeared to be separate from the Dupuytren's foci. The presence of
      hypercellular foci and isolated fibroblasts positive for SM alpha-actin within
      the dermis may explain the high recurrence rate of Dupuytren's disease after
      fasciectomy.

PMID- 8294840
TI  - Incontinentia pigmenti (Bloch-Sulzberger syndrome) manifesting as painful
      periungual and subungual tumours.
AB  - A 25-year-old lady presented with painful periungual tumours which were
      associated with lytic changes of underlying terminal phalanges. She had been
      previously treated as a case of chronic paronychia but the problem recurred. She
      was subsequently diagnosed as a case of Incontinentia pigmenti which is a rare
      genodermatosis with mixed ectodermal and mesodermal polydysplasias,
      onchychodystrophy being a very rare manifestation. She was treated by excision of
      painful finger lesions, but there is no specific treatment for the underlying
      condition.

PMID- 8294841
TI  - Limit of graft length for nerve repair using freeze-thawed muscle grafts with
      great interest.

PMID- 8294842
TI  - Self tolerance of natural MHC class I ligands.

PMID- 8294843
TI  - Rules for peptide presentation by MHC class II molecules.

PMID- 8294844
TI  - Tolerance to self and the processing and presentation of self antigens.
AB  - Antigen processing and presentation is critical to the generation and maintenance
      of self tolerance. The hemoglobin system has provided important data on self
      antigen processing and presentation in vivo. Hemoglobin/Ia complexes were
      detectable in the thymus before the time of positive and negative selection. In
      addition, thymic epithelial cells were shown to lack the costimulatory factors
      necessary to trigger T cell clone proliferation. We have extended these findings
      to the renal proximal tubule. This class II MHC-expressing epithelial cell was
      demonstrated to process and present foreign as well as self antigens to T cell
      hybridomas. Current studies are examining whether this epithelial cell possesses
      the costimulatory factors required to fully stimulate T cell clones, or whether
      the proximal tubule may play an important role in the maintenance of self
      tolerance. In addition we describe the exciting model of murine autoimmune
      myocarditis. We have demonstrated that this is a T cell mediated disease and
      believe that cardiac antigen presenting cells constitutively process and present
      the inciting self antigen, myosin. These studies may provide important insights
      into autoimmunity and self tolerance.

PMID- 8294845
TI  - Presentation of self-peptides: consequences for self nonself discrimination and
      allorecognition.

PMID- 8294846
TI  - Do anergic T cells induce suppressor T lymphocytes through idiotypic
      interactions?
AB  - Suppression by T cells and T cell anergy have been implied, at different periods
      of immunological research, as the main agents of peripheral down regulation of
      the immune response. This article discusses the possibility that anergic T cells,
      with the participation of appropriate co-stimulatory molecules on their
      membranes, stimulate CD8 cells with an alpha/beta TCR specific for peptides of
      the TCR of the anergic cell itself processed and presented by class I MHC. The
      non-anergic (orthoergic) members of the same clone, if activated, process and
      present their TCR in the same way, but, lacking the co-stimulatory molecule, are
      unable to stimulate the anti-idiotype CD8 cells. On the other hand the
      orthoergic, but not the anergic, cells can be induced into death (possibly by
      apoptosis) by the specific CD8 lymphocytes or, alternatively, can be pushed into
      the anergic pool by the same CD8 suppressors, thus contributing to the generation
      of a TCR-restricted circuit in which suppression is dominant. This simple
      immunosuppressive circuit can adequately explain some recent experiments on the
      course of experimental allergic encephalomyelitis. It is to be stressed that many
      elements of the proposal are hypothetical. They are, however, open to
      experimental study.

PMID- 8294847
TI  - Processing and presentation of idiotypes to MHC-restricted T cells.
AB  - Among the self antigens, immunoglobulins, and in particular idiotypes, are of
      special interest because of their extreme sequence heterogeneity and their
      postulated involvement in regulatory interactions in the immune system. We have
      therefore studied antigen processing and presentation of variable region
      peptides, processed idiotypes, to MHC class II molecule-restricted T cells. The
      immunoglobulin used has been the lambda 2(315) light chain produced by the BALB/c
      MOPC 315 plasmacytoma (alpha, lambda 2). The minimum length of a stimulatory
      synthetic idiotypic peptide comprises residues 91-101 of lambda 2(315) and is
      presented by the I-E(d) molecule to CD4+ T cells. T cell clones with specificity
      for the 91-101(lambda 2(315))/I-E(d) complex utilize a limited TCR repertoire and
      are of both Th1 and Th2 type. For presentation, extracellular lambda 2(315)
      requires endocytosis and processing, as previously described for conventional
      exogenous antigens. In addition, a B lymphoma cell can process and present its
      own endogenous lambda 2(315). This was shown by transfecting manipulated lambda
      2(315) gene variants into B lymphoma cells, followed by evaluation of the APC
      function of the transfectants. These studies demonstrated that surface expression
      or secretion of lambda 2(315) is not necessary for presentation and suggested
      that the endoplasmic reticulum may be a processing compartment. To extend our
      findings to naive Id+ B cells and anti-Id T cells, we have generated lambda
      2(315)-transgenic as well as TCR-transgenic mice. A model is presented for a T-B
      cell interaction based on presentation of processed idiotypes.

PMID- 8294848
TI  - Presentation of a circulating self protein (C5) to MHC class II restricted T
      cells.
AB  - Presentation of a soluble self antigen, the fifth component of complement (C5),
      is discussed with emphasis on the differential ability of presentation by
      subpopulations of APC (dendritic cells, macrophages, B cells, fibroblasts, B cell
      lines and bone marrow macrophages). Constitutive presentation of C5 in C5
      sufficient mice is a prerequisite for tolerance induction in MHC class II
      restricted T cells and can be directly demonstrated by the ability of ex-vivo APC
      from C5 sufficient, but not C5 deficient mice, to activate C5 specific T cells in
      vitro in the absence of added antigen. C5 presentation and tolerance induction in
      MHC class II restricted T cells is strictly dependent on an exogenous source of
      self antigen. C5 biosynthesized, but not secreted by macrophages is ignored by
      MHC class II restricted cells and induces neither tolerance nor autoimmunity. C5
      presentation for tolerance induction depends largely on the efficiency of antigen
      uptake by APC, a property which varies within different APC subpopulations and
      with the nature of the antigen.

PMID- 8294849
TI  - Processing of self-proteins and its impact on shaping the T cell repertoire,
      autoimmunity and immune regulation.

PMID- 8294850
TI  - Differential effects of acetylcholine on coronary flow in isolated hypothermic
      hearts from rats and ground squirrels.
AB  - This study was designed to determine whether cholinergic receptors are operative
      in the coronary vessels of a hibernating species (golden mantled ground squirrel,
      Spermophilus lateralis) and a nonhibernating species (rat, Rattus norvegicus)
      under normothermic and hypothermic conditions. Coronary flow and left ventricular
      systolic pressure were measured in isolated perfused hearts from squirrels at 37,
      20 or 7 degrees C and from rats at 37 and 20 degrees C. During cooling, rat
      hearts became arrhythmic and failed between 15 and 12 degrees C. Squirrel hearts
      remained functional at 7 degrees C. Bolus injections of acetylcholine (> 1.0
      microgram) caused significant coronary vasoconstriction in rat hearts at 37 and
      20 degrees C. Similar treatment caused mild coronary vasodilation in squirrel
      hearts at both temperatures. Squirrel hearts did not respond to acetylcholine at
      7 degrees C. The responses in both species were blocked by atropine. Rat coronary
      vessels appear to contain muscarinic constrictor receptors similar to those
      described in humans, sheep, cattle and pigs. The coronary vessels of squirrels,
      by contrast, do not. In this latter species there appears to be a preponderance
      of muscarinic (possibly endothelial-relaxing-factor-linked) dilator receptors.
      Given that acetylcholine acts only as a mild vasodilator at higher temperatures
      in squirrels, parasympathetic regulation of coronary flow in the squirrel heart
      is unlikely, especially during hibernation.

PMID- 8294851
TI  - Excretion in the house cricket: stimulation of rectal reabsorption by homogenates
      of the corpus cardiacum.
AB  - 1. We describe an in vitro perfused preparation of Acheta domesticus rectum which
      allows direct comparison of Malpighian tubule secretion and rectal absorption
      under identical conditions. Rectal absorption is stimulated four- to sixfold by
      corpora cardiaca (CC) homogenates and the stimulated rate is sufficiently rapid
      to account for all the fluid secreted by the tubules. 2. The time course for
      increased fluid absorption is similar to that required to stimulate electrogenic
      chloride transport in locusts and grasshoppers. Chloride is rapidly absorbed by
      the rectum under all conditions, along with lesser amounts of Na+ and K+. Unlike
      the situation in locusts, K+ uptake is unaffected by CC homogenates and the
      stimulated absorbate is NaCl-rich, similar in composition to the NaCl-rich tubule
      fluid produced under stimulated conditions. The absorbate is always slightly hypo
      osmotic to the perfusate, reaching a maximum differential of approximately 15
      mosmol l-1 following CC stimulation. 3. The antidiuretic factor that reduces
      tubule secretion does not promote fluid reabsorption by the rectum.

PMID- 8294852
TI  - Skeletal strain patterns in relation to exercise training during growth.
AB  - Bones are believed to alter their shape in response to changes in tissue strains
      produced by physical activity and the goal of this study is to examine whether
      modeling responses of a growing bone to changes in physical exercise are adjusted
      to maintain a uniform distribution of functional strains. We test this idea by
      comparing in vivo strains recorded in the tibiotarsus of white leghorn chicks
      during 'intensive' treadmill exercise (60% of maximum speed, carrying a weight
      equal to 20% body weight on the trunk: 60%/L) with strains that had been recorded
      previously during 'moderate' treadmill exercise (35% of maximum speed, unloaded:
      35%/UNL) at similar bone sites. Our hypothesis is that modeling adjustments of
      bones subjected to the intensive load-carrying exercise should re-establish
      strains recorded in the bones subjected to moderate exercise. At each exercise
      level, the animals were exercised for 5 days per week (2500 loading cycles per
      day) from 2 to 12 weeks of age. As in the moderate exercise group studied
      earlier, strains measured at six functionally equivalent sites on the tibiotarsus
      of the 60%/L group were consistently maintained during growth from 4 to 12 weeks
      of age. In addition, the pattern of strain recorded at these sites was uniformly
      maintained over the full range of speeds recorded (from 0.48 to 2.70 m s-1 at 12
      weeks of age). Peak strains measured at 4 weeks of age in the load-carrying
      exercise group were initially elevated by 57% overall compared with peak strains
      recorded in the moderate exercise group. At 8 weeks of age, strain levels in the
      60%/L group differed by only 4% overall compared with those recorded in the
      35%/UNL group. The nature of strain (tensile versus compressive) and the
      orientation of principal strain at corresponding sites were also similar in the
      two groups. At 12 weeks of age, however, bone strain levels in the 60%/L group
      were again elevated (47% overall) compared with those recorded in the 35%/UNL
      group, although the general pattern and orientation of strains remained similar.
      This finding suggests a transient modeling response of the bone to the onset of
      exercise training, which was lost during subsequent growth, possibly because the
      normal pattern of functional strain was not altered significantly by the faster
      load-carrying exercise.

PMID- 8294853
TI  - Running springs: speed and animal size.
AB  - Trotting and hopping animals use muscles, tendons and ligaments to store and
      return elastic energy as they bounce along the ground. We examine how the
      musculoskeletal spring system operates at different speeds and in animals of
      different sizes. We model trotting and hopping as a simple spring-mass system
      which consists of a leg spring and a mass. We find that the stiffness of the leg
      spring (k(leg)) is nearly independent of speed in dogs, goats, horses and red
      kangaroos. As these animals trot or hop faster, the leg spring sweeps a greater
      angle during the stance phase, and the vertical excursion of the center of mass
      during the ground contact phase decreases. The combination of these changes to
      the spring system causes animals to bounce off the ground more quickly at higher
      speeds. Analysis of a wide size range of animals (0.1-140 kg) at equivalent
      speeds reveals that larger animals have stiffer leg springs (k(leg) [symbol: see
      text] M0.67, where M is body mass), but that the angle swept by the leg spring is
      nearly independent of body mass. As a result, the resonant period of vertical
      vibration of the spring-mass system is longer in larger animals. The length of
      time that the feet are in contact with the ground increases with body mass in
      nearly the same way as the resonant period of vertical vibration.

PMID- 8294854
TI  - A triple tribute to the experiment that transformed biology.

PMID- 8294855
TI  - A retrospective look: how we identified the pneumococcal transforming substance
      as DNA.

PMID- 8294856
TI  - Comparison of somatic mutation frequency among immunoglobulin genes.
AB  - We analyzed the frequency of somatic mutation in immunoglobulin genes from
      hybridomas that secrete anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) monoclonal
      antibodies. A high frequency of mutation (3.3-4.4%) was observed in both the
      rearranged VH186.2 and V lambda 1 genes, indicating that somatic mutation occurs
      with similar frequency in these genes in spite of the absence of an intron
      enhancer in lambda 1 chain genes. In contrast to the high frequency in J-C
      introns, only two nucleotide substitutions occurred at positions -462 and -555 in
      the 5' noncoding region in one of the lambda 1-chain genes and in none of the
      other three so far studied. Since a similar low frequency of somatic mutation was
      observed in the 5' noncoding region of inactive lambda 2-chain genes rendered
      inactive because of incorrect rearrangement, this region may not be a target or
      alternatively, may be protected from the mutator system. We observed a low
      frequency of nucleotide substitution in unrearranged V lambda 1 genes
      (approximately 1/15 that of rearranged genes). Together with previous results
      (Azuma T., N. Motoyama, L. Fields, and D. Loh, 1993. Int. Immunol. 5:121), these
      findings suggest that the 5' noncoding region, which contains the promoter
      element, provides a signal for the somatic mutator system and that rearrangement,
      which brings the promoter into close proximity to the enhancer element, should
      increase mutation efficiency.

PMID- 8294857
TI  - Clearance of NH2-terminal propeptides of types I and III procollagen is a
      physiological function of the scavenger receptor in liver endothelial cells.
AB  - This study was undertaken to determine the fate of circulating NH2-terminal
      propeptide of type I procollagen (PINP) in rats. Radiolabeled PINP showed a
      biphasic serum decay curve after intravenous injection. 79% of the material
      disappeared from the blood during the initial alpha-phase (t1/2 alpha = 0.6 min),
      while the remaining 21% was eliminated with a t1/2 beta of 3.3 min. The major
      site of uptake was the liver, 78, 1, and 21% of its radioactivity being recovered
      in isolated liver endothelial cells (LEC), Kupffer cells, and parenchymal cells,
      respectively. In LEC, fluorescently labeled PINP accumulated in small (0.1
      microns) peripheral and larger (> 0.1 microns) perinuclear vesicles within 10 min
      at 37 degrees C after a binding pulse at 4 degrees C. These grew in size with
      increasing chasing time, reaching a maximum diameter of 1 microns or more after
      30 min, and taking the shape of rings that were stained only along their
      periphery. At chase intervals exceeding 30 min, the size of the vesicles
      decreased, and after 60 min the stain appeared in smaller, densely stained
      perinuclearly located vesicles. Degradation of 125I-PINP to free smaller
      fragments and 125I- was significant after 30 min. Only formaldehyde-treated
      albumin, acetylated LDL, polyinosinic acid and NH2-terminal propeptide of type
      III procollagen (PIIINP) competed with PINP for uptake. These findings indicate
      that clearance of PINP and PIIINP, which are normal waste products generated in
      large quantities, is a physiological function of the scavenger receptor in LEC.

PMID- 8294858
TI  - Immunoglobulin signal transduction guides the specificity of B cell-T cell
      interactions and is blocked in tolerant self-reactive B cells.
AB  - The specificity of antibody (Ab) responses depends on focusing helper T (Th)
      lymphocyte signals to suitable B lymphocytes capable of binding foreign antigens
      (Ags), and away from nonspecific or self-reactive B cells. To investigate the
      molecular mechanisms that prevent the activation of self-reactive B lymphocytes,
      the activation requirements of B cells specific for the Ag hen egg lysozyme (HEL)
      obtained from immunoglobulin (Ig)-transgenic mice were compared with those of
      functionally tolerant B cells isolated from Ig-transgenic mice which also express
      soluble HEL. To eliminate the need for surface (s)Ig-mediated Ag uptake and
      presentation and allow the effects of sIg signaling to be studied in isolation,
      we assessed the ability of allogeneic T cells from bm12 strain mice to provide in
      vivo help to C57BL/6 strain-transgenic B cells. Interestingly, non-tolerant Ig
      transgenic B cells required both allogeneic Th cells and binding of soluble HEL
      for efficient activation and Ab production. By contrast, tolerant self-reactive B
      cells from Ig/HEL double transgenic mice responded poorly to the same combination
      of allogeneic T cells and soluble HEL. The tolerant B cells were nevertheless
      normally responsive to stimulation with interleukin 4 and anti-CD40 Abs in vitro,
      suggesting that they retained the capacity to respond to mediators of T cell
      help. However, the tolerant B cells exhibited a proximal block in the sIg
      signaling pathway which prevented activation of receptor-associated tyrosine
      kinases in response to the binding of soluble HEL. The functional significance of
      this sIg signaling defect was confirmed by using a more potent membrane-bound
      form of HEL capable of triggering sIg signaling in tolerant B cells, which
      markedly restored their ability to collaborate with allogeneic Th cells and
      produce Ab. These findings indicate that Ag-specific B cells require two signals
      for mounting a T cell-dependent Ab response and identify regulation of sIg
      signaling as a mechanism for controlling self-reactive B cells.

PMID- 8294859
TI  - The mouse mammary tumor virus envelope gene product is required for superantigen
      presentation to T cells.
AB  - Transgenic mice expressing either the mouse mammary tumor virus (MMTV)
      superantigen gene (sag) alone or in combination with the viral envelope genes
      (env) (LEL), or all of the viral genes (gag, pol, env, and sag) (HYB PRO),
      deleted V beta 14+ T cells from their immune repertoire. However, only LEL or HYB
      PRO transgenic antigen-presenting cells were capable of stimulating a
      proliferative response from nontransgenic primary T cells or interleukin 2
      production from a V beta 15-bearing T cell hybridoma. These T cell responses
      could be inhibited by a monospecific antibody directed against the MMTV gp52 cell
      surface glycoprotein. These results indicate that the MMTV gp52 gene product
      participates in the presentation of superantigen to T cells, resulting in their
      stimulation, a requisite step in the MMTV infection pathway. Thus, gp52 could
      play a role in the transfer of virus between different subsets of lymphocytes.

PMID- 8294860
TI  - Characterization of human immunodeficiency virus type 1-specific cytotoxic T
      lymphocyte clones isolated during acute seroconversion: recognition of autologous
      virus sequences within a conserved immunodominant epitope.
AB  - Virus-specific cytotoxic T lymphocytes (CTL) are involved in protective immunity
      to many virus infections. It has recently been shown that CTL are detectable
      early during primary infection with the primate lentiviruses, human
      immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus. To
      better characterize the CTL response during acute HIV-1 infection, HIV-1-specific
      CTL clones were generated from two patients during symptomatic HIV-1
      seroconversion. These CTL clones demonstrated specificity for env of HIV-1 and
      recognized sequences within gp41. Two human histocompatibility leukocyte antigen
      (HLA) A31-restricted clones from the same individual were found to have differing
      virus strain specificities. Both clones recognized the 11-amino acid peptide
      RLRDLLLIVTR from position 770-780 of gp41. A change from T to V at position 779
      in this epitope abrogated lysis by one clone but not the other. A CTL clone from
      the other patient, restricted by a different class I HLA allele, recognized the
      nine-amino acid peptide HRLRDLLLI from position 769-777 of gp41. Of note, the
      peptide RLRDLLLIVTR has been shown by others to be presented to CTL by HLA-A3.1.
      Autologous virus sequences from seroconversion and up to 15 wk after presentation
      in these two patients were recognized by the CTL clones isolated during acute
      infection. None of the CTL clones recognized the MN strain of HIV-1, indicating
      the problems inherent in relying on a single virus strain in the development of a
      vaccine. These studies have identified an immunodominant and promiscuous area for
      the generation of CTL responses within gp41. This recognition of autologous virus
      sequences by the initial CTL response is consistent with the hypothesis that a
      single virus strain is transmitted to the seroconverter and that the CTL response
      is involved in the initial control of that virus. These studies indicate the
      importance of the CTL response to HIV-1 infection and have implications in the
      design of vaccines.

PMID- 8294861
TI  - Lysis of ras oncogene-transformed cells by specific cytotoxic T lymphocytes
      elicited by primary in vitro immunization with mutated ras peptide.
AB  - Ras protooncogenes are activated by characteristic point mutations in a wide
      variety of malignancies. The expressed p21ras proteins are oncogenic by virtue of
      single substituted amino acids, usually at position 12 or 61 of the 189-residue
      p21ras protein. In the current study, the ability of class I major
      histocompatibility complex (MHC)-restricted T cells to recognize the altered
      segment of a transforming p21ras protein and to lyse cells transformed by the
      corresponding ras oncogene was examined. Synthetic ras peptides encompassing the
      common activating substitution of leucine for glutamine at position 61 were
      constructed with an amino acid motif appropriate for binding to the H-2Kb murine
      class I MHC molecule. Cytotoxic T lymphocytes (CTL) specific for bound ras
      leucine 61 peptide were elicited by in vitro immunization of normal lymphocytes
      with synthetic peptides. The ras peptide-induced CTL specifically lysed syngeneic
      fibroblasts transformed by an activated ras gene encoding oncogenic p21ras
      protein containing the same single amino acid substitution. Thus, in some
      circumstances, mutated p21ras protein can serve as a tumor-specific antigen.

PMID- 8294862
TI  - "Anergy" of TH0 helper T lymphocytes induces downregulation of TH1
      characteristics and a transition to a TH2-like phenotype.
AB  - Mature CD4+ helper T lymphocytes have been categorized into two major functional
      phenotypes, TH1 and TH2, which produce distinct arrays of lymphokines and which
      are thought to arise from a pluripotential precursor cell termed TH0. Clonal
      anergy can be induced in TH1 clones by stimulating via the T cell receptor (TCR)
      complex in the absence of a costimulator molecule; however, anergy has been
      difficult to demonstrate in TH2 clones. We show here that treatment of cloned TH0
      lines with anergizing stimuli results in the selective loss of TH1
      characteristics and retention of a TH2 phenotype. Treated cells exhibit a
      substantial reduction in interleukin 2 (IL-2) production and antigen-specific
      cytolytic activity, but retain comparable IL-4 and IL-5 production in response to
      restimulation via the TCR complex. TH0 clones exposed to anergizing stimuli also
      increase in size, thus morphologically resembling TH2 cells. The signaling
      characteristics of these cells also are altered, in that they exhibit an elevated
      basal level of intracellular free calcium which fails to increase significantly
      with subsequent restimulation, reminiscent of the signaling characteristics of
      TH2 cells. "Anergized" TH0 clones thus share several functional, morphologic, and
      physiologic properties with cells of the TH2 phenotype, suggesting that TH2 cells
      may arise when TH0 cells are stimulated via the TCR complex in the absence of a
      putative costimulator molecule.

PMID- 8294863
TI  - Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice
      after peripheral inoculation with HIV-1.
AB  - A small animal model that could be infected with human immunodeficiency virus 1
      (HIV-1) after peripheral inoculation would greatly facilitate the study of the
      pathophysiology of acute HIV-1 infection. The utility of SCID mice implanted with
      human fetal thymus and liver (SCID-hu mice) for studying peripheral HIV-1
      infection in vivo has been hampered by the requirement for direct intraimplant
      injection of HIV-1 and the continued restriction of the resultant HIV-1 infection
      to the human thymus and liver (hu-thy/liv) implant. This may have been due to the
      very low numbers of human T cells present in the SCID-hu mouse peripheral
      lymphoid compartment. Since the degree of the peripheral reconstitution of SCID
      hu mice with human T cells may be a function of the hu-thy/liv implant size, we
      increased the quantity of hu-thy/liv tissue implanted under the renal capsule and
      implanted hu-thy/liv tissue under the capsules of both kidneys. This resulted in
      SCID-hu mice in which significant numbers of human T cells were detected in the
      peripheral blood, spleens, and lymph nodes. After intraimplant injection of HIV-1
      into these modified SCID-hu mice, significant HIV-1 infection was detected by
      quantitative coculture not only in the hu-thy/liv implant, but also in the spleen
      and peripheral blood. This indicated that HIV-1 infection can spread from the
      thymus to the peripheral lymphoid compartment. More importantly, a similar degree
      of infection of the hu-thy/liv implant and peripheral lymphoid compartment
      occurred after peripheral intraperitoneal inoculation with HIV-1. Active viral
      replication was indicated by the detection of HIV-1 gag DNA, HIV-1 gag RNA, and
      spliced tat/rev RNA in the hu-thy/liv implants, peripheral blood mononuclear
      cells (PBMC), spleens, and lymph nodes of these HIV-1-infected SCID-hu mice. As a
      first step in using our modified SCID-hu mouse model to investigate the
      pathophysiological consequences of HIV-1 infection, the effect of HIV-1 infection
      on the expression of human cytokines shown to enhance HIV-1 replication was
      examined. Significantly more of the HIV-1-infected SCID-hu mice expressed mRNA
      for human tumor necrosis factors alpha and beta, and interleukin 2 in their
      spleens, lymph nodes, and PBMC than did uninfected SCID-hu mice. This suggested
      that HIV-1 infection in vivo can stimulate the expression of cytokine mRNA by
      human T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294864
TI  - Peptide length and sequence specificity of the mouse TAP1/TAP2 translocator.
AB  - The transporter associated with antigen processing (TAP) delivers peptides to the
      lumen of the endoplasmic reticulum in an adenosine triphosphate (ATP) dependent
      fashion for presentation by major histocompatibility complex class I molecules.
      We show that the mouse TAP translocator (H-2b haplotype) selects peptides based
      on a minimal size of nine residues, and on the presence of a hydrophobic COOH
      terminal amino acid. The preponderance of COOH-terminal hydrophobic amino acids
      in peptides capable of binding to mouse class I molecules thus fits remarkably
      well with the specificity of the TAP translocator. In addition to transport in
      the lumenal direction, efflux of peptide in the cytosolic direction is observed
      in an ATP- and temperature-dependent manner. By maintaining a low peptide
      concentration at the site of class I assembly, this efflux mechanism may ensure
      that class I molecules are loaded preferentially with high affinity peptides.

PMID- 8294865
TI  - A mutant human histocompatibility leukocyte antigen DR molecule associated with
      invariant chain peptides.
AB  - From a human histocompatibility leukocyte antigen (HLA)-DR/DQ hemizygous, B
      lymphoblastoid progenitor, we isolated a cell line, 10.24.6, with a DR alpha
      missense mutation (96P-->96S), which results in an N-linked carbohydrate addition
      at position 94 in the DR alpha 2 domain. Several features of 10.24.6 cells
      suggest that the mutation disrupts normal intracellular formation of peptide/DR
      complexes. The mutant HLA-DR dimers, though expressed at the cell surface, lack
      the conformation of the mature, peptide-loaded class II molecules of the
      progenitor cell, as assessed by their loss of binding of certain antibodies and
      by the lack of stability in detergent (sodium dodecyl sulfate) solution. In
      addition, presentation of endocytosed antigen to HLA-DR-restricted T cells is
      defective in the mutant, but can be restored by transfection of a wild type DRA
      gene. Assays with synthetic peptides indicate that the 10.24.6 phenotype is not
      due to an intrinsic inability of the mutant DR molecules to bind peptides.
      Therefore, to directly evaluate peptide occupancy of the mutant molecules, we
      analyzed acid-eluted, HLA-DR-associated peptides. The predominant species from
      the 10.24.6 mutant is a nested set of invariant chain (Ii)-derived peptides that
      are undetectable in the DR eluate from progenitor cells. The region of DR alpha
      altered in the mutant molecules is thus implicated in normal formation of
      peptide/DR complexes. Further, the same set of Ii peptides associated with the DR
      molecules is present in the eluate from an antigen presentation mutant with a
      defect in an major histocompatibility complex (MHC)-linked gene. These results
      suggest that DR molecules in 10.24.6 and in certain presentation mutants are
      affected at the same or related steps in class II molecule biosynthesis, raising
      the possibility that class II molecules interact with an MHC-encoded accessory
      molecule during antigen presentation.

PMID- 8294866
TI  - Phosphatidylinositol-3 kinase activation induced upon Fc gamma RIIIA-ligand
      interaction.
AB  - Induced activation of protein tyrosine kinase(s) is a central event in signal
      transduction mediated via the low affinity receptor for IgG (Fc gamma RIIIA,
      CD16) in natural killer (NK) cells. Tyrosine phosphorylation may affect the
      function of several protein directly, or indirectly by inducing their association
      with other tyrosine phosphorylated proteins. Here, we report that Fc gamma RIII
      stimulation induces activation of phosphatidylinositol (PI)-3 kinase in NK cells.
      Phosphotyrosine immunoprecipitates from Fc gamma RIII-stimulated NK cells contain
      PI-kinase activity and PI-3 kinase can be directly precipitated from them.
      Conversely, a series of tyrosine-phosphorylated proteins is coprecipitated with
      PI-3 kinase from the stimulated, but not from control cells. Analogous results
      obtained using Jurkat T cells expressing transfected Fc gamma RIIIA alpha ligand
      binding chain in association with gamma 2 or zeta 2 homodimers indicate that both
      complexes transduce this effect, although the Fc gamma RIIIA-zeta 2 complexes do
      so with greater efficiency. Accumulation of phosphoinositide D3 phosphorylated
      products in stimulated cells confirms PI-3 kinase activation, indicating the
      participation of this enzyme in Fc gamma RIIIA-mediated signal transduction.

PMID- 8294867
TI  - Separate metabolic pathways leading to DNA fragmentation and apoptotic chromatin
      condensation.
AB  - Apoptosis is the predominant form of cell death observed in a variety of
      physiological and pathological conditions such as cancer involution, insect
      metamorphosis, the development of the immune and nervous systems, and
      embryogenesis. The typical nuclear changes taking place in apoptotic cells
      include extensive condensation of chromatin and internucleosomal DNA
      fragmentation into units of 200 base pairs. However, the mechanisms responsible
      for both chromatin condensation and DNA fragmentation have yet to be elucidated.
      In this study, micrococcal nuclease and the divalent cations, Ca2+ and Mg2+, were
      applied to isolated nuclei in an attempt to reconstitute in vitro the digestion
      of genomic DNA associated with apoptosis. Micrococcal nuclease was found to
      induce a typical pattern of DNA fragmentation, but did not give rise to chromatin
      condensation, whereas Ca2+/Mg2+ induced both chromatin condensation and DNA
      fragmentation in isolated mouse liver nuclei. When the endonuclease inhibitor
      ZnCl2 was used, the DNA fragmentation induced by Ca2+/Mg2+ in nuclei could be
      completely inhibited, but chromatin condensation still occurred. For comparison,
      intact liver cells were treated with valinomycin, a potassium ionophore, which
      gave rise to an atypical cell death, with chromatin condensation appearing
      without DNA fragmentation. Our results suggest that endonuclease activation in
      apoptosis is neither necessary nor sufficient to induce chromatin condensation,
      and that DNA fragmentation and chromatin condensation may be triggered through
      separate pathways during apoptosis.

PMID- 8294868
TI  - The third component of complement protects against Escherichia coli endotoxin
      induced shock and multiple organ failure.
AB  - We investigated whether the third component of complement (C3) is involved in the
      pathophysiology of endotoxic shock, and if it is involved, whether it plays a
      protective role or whether it mediates shock and multiple organ failure. In a
      prospective, controlled investigation, six Brittany spaniels that were homozygous
      for a genetically determined deficiency of C3 (C3 deficient, < 0.003% of normal
      serum C3 levels) and six heterozygous littermates (controls, approximately 50% of
      mean normal serum C3 level) were given 2 mg/kg of reconstituted Escherichia coli
      026:B6 acetone powder as a source of endotoxin, intravenously. All animals were
      given similar fluid and prophylactic antibiotic therapy, and had serial
      hemodynamic variables obtained. After E. coli endotoxin infusion, C3-deficient
      animals had higher peak levels of endotoxin and less of a rise in temperature
      than controls (P < 0.05). During the first 4 h after E. coli endotoxin infusion,
      C3-deficient animals had significantly greater decreases in mean central venous
      pressure and mean pulmonary artery pressure than controls (P < 0.02). During the
      first 48 h after E. coli endotoxin infusion, C3-deficient animals had
      significantly greater decreases in mean arterial pH, left ventricular ejection
      fraction, and mean pulmonary capillary wedge pressure, and greater increases in
      mean arterial lactate, arterial-alveolar O2 gradient, and transaminases
      (aspartate aminotransferase and alanine aminotransferase) than controls, (all P <
      0.05). After E. coli endotoxin infusion, C3-deficient animals compared to
      controls had significantly less of a decrease in mean C5 levels (P < 0.01), but
      similar (P = NS) increases in circulating tumor necrosis factor levels,
      bronchoalveolar lavage neutrophils, and protein, and similar (P = NS) decreases
      in blood leukocytes and platelets. Two of six C3-deficient animals and two of six
      controls died. In summary, after intravenous infusion of E. coli endotoxin,
      canines with C3 deficiency have decreased endotoxin clearance and worse E. coli
      endotoxin-induced shock and organ damage. Thus, the third component of the
      complement system plays a beneficial role in the host defense against E. coli
      endotoxic shock.

PMID- 8294869
TI  - A nonpolymorphic major histocompatibility complex class Ib molecule binds a large
      array of diverse self-peptides.
AB  - Unlike the highly polymorphic major histocompatibility complex (MHC) class Ia
      molecules, which present a wide variety of peptides to T cells, it is generally
      assumed that the nonpolymorphic MHC class Ib molecules may have evolved to
      function as highly specialized receptors for the presentation of structurally
      unique peptides. However, a thorough biochemical analysis of one class Ib
      molecule, the soluble isoform of Qa-2 antigen (H-2SQ7b), has revealed that it
      binds a diverse array of structurally similar peptides derived from intracellular
      proteins in much the same manner as the classical antigen-presenting molecules.
      Specifically, we find that SQ7b molecules are heterodimers of heavy and light
      chains complexed with nonameric peptides in a 1:1:1 ratio. These peptides contain
      a conserved hydrophobic residue at the COOH terminus and a combination of one or
      more conserved residue(s) at P7 (histidine), P2 (glutamine/leucine), and/or P3
      (leucine/asparagine) as anchors for binding SQ7b. 2 of 18 sequenced peptides
      matched cytosolic proteins (cofilin and L19 ribosomal protein), suggesting an
      intracellular source of the SQ7b ligands. Minimal estimates of the peptide
      repertoire revealed that at least 200 different naturally processed self-peptides
      can bind SQ7b molecules. Since Qa-2 molecules associate with a diverse array of
      peptides, we suggest that they function as effective presenting molecules of
      endogenously synthesized proteins like the class Ia molecules.

PMID- 8294870
TI  - Salmonella stimulate macrophage macropinocytosis and persist within spacious
      phagosomes.
AB  - Light microscopic studies of phagocytosis showed that Salmonella typhimurium
      entered mouse macrophages enclosed in spacious phagosomes (SP). Viewed by time
      lapse video microscopy, bone marrow-derived macrophages exposed to S. typhimurium
      displayed generalized plasma membrane ruffling and macropinocytosis. Phagosomes
      containing Salmonella were morphologically indistinguishable from macropinosomes.
      SP formation was observed after several methods of bacterial opsonization,
      although bacteria opsonized with specific IgG appeared initially in small
      phagosomes that later enlarged. In contrast to macropinosomes induced by growth
      factors, which shrink completely within 15 min, SP persisted in the cytoplasm,
      enlarging often by fusion with macropinosomes or other SP. A Salmonella strain
      containing a constitutive mutation in the phoP virulence regulatory locus (PhoPc)
      induced significantly fewer SP. Similar to Yersinia enterocolitica, PhoPc
      bacteria entered macrophages in close-fitting phagosomes, consistent with that
      expected for conventional receptor-mediated phagocytosis. These results suggest
      that formation of SP contributes to Salmonella survival and virulence.

PMID- 8294871
TI  - Clonal populations of T cells in normal elderly humans: the T cell equivalent to
      "benign monoclonal gammapathy".
AB  - To determine whether T cells, like B cells, can become clonally expanded in
      normal individuals as a function of age, we compared the T cell V beta repertoire
      of cord blood to that of peripheral blood from normal donors over 65 yr of age. T
      cells from elderly subjects contained expanded subsets (greater than the
      mean+three standard deviations) of T cell receptor (TCR) V beta populations.
      These expanded subsets were observed primarily among CD8, but not CD4 cells,
      represented up to 37.5% of all CD8 cells, and were present in most elderly
      subjects. An expanded V beta 5.2/3 CD8 subset and a V beta 6.7a CD8 subset from
      separate donors were analyzed by reverse transcriptase-polymerase chain reaction,
      cloning and sequencing of the TCR beta chain VDJ junction. In both cases the
      expanded subsets were mono- or oligoclonal while control CD4 populations were
      polyclonal. Using two-color flow cytometry it was possible to identify the
      expanded V beta 6.7a subset as CD8+ CD28-CD11b+ cells. In three of five random
      old subjects similar expansions of V beta subsets were found specifically in the
      CD8+ CD28- subpopulation, an interesting subset of cytotoxic T lymphocytes, known
      to lack proliferative responses to TCR stimuli. It is common practice to use the
      demonstration of clonality as a diagnostic indicator for T cell
      lymphoma/leukemia. In view of the high frequency of expanded T clones of T cells
      in normal elderly subjects the diagnostic usefulness of this test should be
      reexamined.

PMID- 8294872
TI  - Variability of a bacterial surface protein and disease expression in a possible
      mouse model of systemic Lyme borreliosis.
AB  - During persistent infection of scid mice with Borrelia turicatae, an agent of
      relapsing fever and neuroborreliosis, there was variation in the surface proteins
      the bacteria expressed and in disease manifestations over time. Two serotypes, A
      and B, were isolated from the mice, cloned by limiting dilution, and further
      characterized. The only discernible difference between the two variants was in
      the size of the major surface protein they expressed: serotype A had a variable
      major protein (Vmp) of 23,000, and serotype B had a Vmp of 20,000. When other
      scid mice were inoculated with clonal populations of A and B, the infections were
      similar with respect to onset and degree of spirochetemia, involvement of the eye
      and heart, and occurrence of a peripheral vestibular disorder. However, there
      were differences between the serotypes in other respects: (a) serotype B but not
      A caused reddened and significantly enlarged joints, markedly impaired
      performance on a walking bar, and severe arthritis by histologic examination; (b)
      serotype A but not B invaded the central nervous system during early infection;
      and (c) serotype A penetrated monolayers of human umbilical vein endothelial
      cells more readily than did serotype B. The combination of arthritis,
      myocarditis, and neurologic disease resembled human Lyme borreliosis. The
      findings indicate that differences in disease expression are determined by
      variable surface proteins of the bacterium and that scid mouse infections with B.
      turicatae provide a model for the study of the pathogenesis of Lyme borreliosis
      and other persistent spirochetal diseases.

PMID- 8294873
TI  - Macrophage inflammatory protein 1 alpha, interleukin 3 and diffusible marrow
      stromal factors maintain human hematopoietic stem cells for at least eight weeks
      in vitro.
AB  - Factors that induce proliferation of the human hematopoietic stem cell are ill
      defined. Primitive hematopoietic progenitors can be maintained and differentiate
      in stroma-dependent, long-term bone marrow cultures (LTBMC), originally described
      by Dexter et al. (Dexter, T. M., L. H. Coutinho, E. Spooncer, C. M. Heyworth, C.
      P. Daniel, R. Schiro, J. Chang, and T. D. Allen. 1990. Molecular Control of
      Haemopoiesis). However, 70-80% of primitive progenitors capable of reinitiating
      secondary stromal cultures (LTBMC-initiating cells [IC]) are lost over a period
      of 5 wk in such cultures. We have recently described a novel "stroma-noncontact"
      culture system, in which hematopoietic progenitors are separated from the stromal
      layer by a 0.4-micron microporous filter membrane. Primitive progenitors in such
      cultures can not only differentiate into committed progenitors, but are also
      maintained to a greater extent than in "Dexter" cultures. However, still only 50%
      of the originally seeded LTBMC-IC are recovered at week 5. Since maintenance of
      primitive progenitors may depend not only on growth-promoting factors but also on
      factors that inhibit differentiation and/or proliferation, we evaluated the
      effect of macrophage inflammatory protein 1 alpha (MIP-1 alpha) or "stem cell
      inhibitor" in combination with the growth-inducing factor interleukin 3 (IL-3) on
      the recovery of LTBMC-IC from stroma-noncontact cultures. We demonstrate that
      addition of MIP-1 alpha alone to stroma-noncontact cultures does not change the
      number of LTBMC-IC present after 8 wk, indicating that this factor may not
      directly inhibit or stimulate proliferation of primitive progenitors. Addition of
      the growth stimulatory cytokine, IL-3, alone results in exhaustion of LTBMC-IC
      after 8 wk of culture, possibly as a result of their terminal differentiation.
      However, LTBMC-IC can be maintained for at least 8 wk when grown in stroma
      noncontact cultures supplemented with both MIP-1 alpha plus IL-3. This effect
      depends on soluble (ill-defined) stromal factors, and results from a direct
      interaction of these cytokines with the progenitor population or its progeny, but
      not the stroma.

PMID- 8294874
TI  - The CD8+ T cell repertoire in beta 2-microglobulin-deficient mice is biased
      towards reactivity against self-major histocompatibility class I.
AB  - Beta 2-Microglobulin-deficient (beta 2m -/-) mice are reported to lack cell
      surface expression of major histocompatibility complex (MHC) class I molecules,
      CD8+ T cells, and the ability to mount MHC class I-specific T cell responses. We
      have observed that beta 2m -/- mice possess CD8+ T cells that can be induced to
      perform strong allospecific cytotoxic responses against nonself-MHC class I by in
      vivo priming. We report that these beta 2m -/- cytotoxic T lymphocyte (CTL)
      differ from those induced in beta 2m-positive littermates in that they cross
      react and kill cells expressing self-MHC class I at normal ligand density with
      beta 2m. beta 2m -/- CTL could even be induced in primary mixed lymphocyte
      culture by self-MHC class I expressing stimulator cells, whereas allogeneic
      stimulator cells failed to elicit a response under similar conditions. Cells with
      a reduced cell surface MHC class I expression were less sensitive, while
      syngeneic beta 2m -/- cells were resistant to the beta 2m -/- CTL. This antiself
      MHC reactivity could not be induced when beta 2m -/- T cells matured in an
      environment with normal MHC class I expression in bone marrow chimeric mice.
      Antiself-MHC reactivity was also observed against human peptide loading-deficient
      cells expressing the appropriate murine class I molecules, suggesting that
      affinity to self-MHC class I may occur irrespective of peptide content. The
      results fit with a model where positive and negative selection of CD8+ T cells in
      beta 2m -/- mice is mediated by low levels of MHC class I free heavy chains. In
      this model, low ligand density on selecting cells leads to positive selection of
      rare T cells that bind to low levels of MHC class I free heavy chains, resulting
      in a very small peripheral CD8+ compartment. Due to low density of the selecting
      ligand, negative selection does not remove T cells recognizing beta 2m-positive
      cells expressing self-MHC class I at normal ligand density, which generates a T
      cell repertoire that would be autoreactive in a beta 2m-positive littermate. The
      first "MHC deficient" animals thus paradoxically provide a tool for direct
      demonstration and analysis of self MHC bias in the T cell repertoire.

PMID- 8294876
TI  - Rapid clearance of malaria circumsporozoite protein (CS) by hepatocytes.
AB  - The circumsporozoite protein (CS) covers uniformly the plasma membrane of malaria
      sporozoites. In vitro, CS multimers bind specifically to regions of the
      hepatocyte plasma membrane that are exposed to circulating blood in the Disse
      space. The ligand is in the region II-plus of CS, an evolutionarily conserved
      stretch of the protein that has amino acid sequence homology to a cell adhesive
      motif of thrombospondin. We have now found that intravenously injected CS
      constructs bind rapidly to the basolateral surface of hepatocytes, provided that
      the recombinant proteins contain region II-plus, and that they are aggregated.
      Significant amounts of CS were not retained in any other organ. The striking
      parallelism between these in vitro and in vivo findings with the target
      specificity of malaria sporozoites, reinforces the hypothesis that the attachment
      of the parasites to hepatocytes is via region II-plus of CS.

PMID- 8294877
TI  - Interleukin 5 synthesis by eosinophils: association with granules and
      immunoglobulin-dependent secretion.
AB  - Interleukin 5 (IL-5) is the main factor that promotes the terminal
      differentiation of eosinophil progenitors (as indicated by colony formation
      assays), and enhances the effector capacity of mature eosinophils. IL-5 is
      produced by T lymphocytes, CD4-/CD8- and mast cells and recently, messenger
      (m)RNA of this cytokine has been identified in eosinophils from patients with
      coeliac disease, asthma, or eosinophilic heart diseases. In this study, IL-5 mRNA
      and immunoreactive IL-5 protein were detected in tissue and blood eosinophils
      from patients with eosinophilic cystitis or hypereosinophilic syndromes but not
      in Crohn's disease. By electron microscopy associated to immunogold staining,
      immunoreactive IL-5 was identified in eosinophilic granules. After stimulation
      with IgA-, IgE-, or IgG-immune complexes, blood eosinophils were shown, by
      immunocytochemistry and by enzyme-linked immunosorbent assay, to secrete IL-5.
      These observations demonstrate that eosinophils, under physiological stimulation,
      can release significant amounts of IL-5, which may contribute to local eosinophil
      recruitment and activation.

PMID- 8294875
TI  - The invariant chain is required for intracellular transport and function of major
      histocompatibility complex class II molecules.
AB  - The major histocompatibility complex (MHC) class II-associated invariant chain
      (Ii) is thought to act as a chaperone that assists class II during folding,
      assembly, and transport. To define more precisely the role of Ii chain in
      regulating class II function, we have investigated in detail the biosynthesis,
      transport, and intracellular distribution of class II molecules in splenocytes
      from mice bearing a deletion of the Ii gene. As observed previously, the absence
      of Ii chain caused significant reduction in both class II-restricted antigen
      presentation and expression of class II molecules at the cell surface because of
      the intracellular accumulation of alpha and beta chains. Whereas much of the
      newly synthesized MHC molecules enter a high molecular weight aggregate
      characteristic of misfolded proteins, most of the alpha and beta chains form
      dimers and acquire epitopes characteristic of properly folded complexes. Although
      the complexes do not bind endogenously processed peptides, class II molecules
      that reach the surface are competent to bind peptides added to the medium,
      further demonstrating that at least some of the complexes fold properly. Similar
      to misfolded proteins, however, the alpha and beta chains are poorly terminally
      glycosylated, suggesting that they fail to reach the Golgi complex. As
      demonstrated by double label confocal and electron microscope
      immunocytochemistry, class II molecules were found in a subcompartment of the
      endoplasmic reticulum and in a population of small nonlysosomal vesicles possibly
      corresponding to the intermediate compartment or cis-Golgi network. Thus,
      although alpha and beta chains can fold and form dimers on their own, the absence
      of Ii chain causes them to be recognized as "misfolded" and retained in the same
      compartments as bona fide misfolded proteins.

PMID- 8294878
TI  - Negative selection of CD4+CD8+ thymocytes by T cell receptor-induced apoptosis
      requires a costimulatory signal that can be provided by CD28.
AB  - CD4+CD8+ thymocytes expressing self-reactive T cell antigen receptors (TCR) are
      deleted in the thymus as a consequence of TCR/self-antigen/major
      histocompatibility complex interactions. However, the signals that are necessary
      to initiate clonal deletion have not yet been clarified. Here we demonstrate that
      TCR engagement does not efficiently induce apoptosis of CD4+CD8+ thymocytes,
      although it generates signals that increase expression of CD5, a thymocyte
      differentiation marker. In fact, TCR signals fail to induce thymocyte apoptosis
      even when augmented by simultaneous engagement with CD4 or lymphocyte function 1
      associated molecules. In marked contrast, signals generated by engagement of both
      TCR and the costimulatory molecule CD28 potently induce apoptosis of CD4+CD8+
      thymocytes. Thus, the present results define a requirement for both TCR and
      costimulatory signals for thymocyte apoptosis and identify CD28 as one molecule
      that is capable of providing the necessary costimulus. These results provide a
      molecular basis for differences among cell types in their ability to mediate
      negative selection of developing thymocytes.

PMID- 8294879
TI  - Evidence for differential intracellular signaling via CD4 and CD8 molecules.
AB  - Although both the CD4 and CD8 molecules enhance antigen responsiveness mediated
      by the T cell receptor (TCR), it is not known whether CD4 and CD8 initiate
      similar or different intracellular signals when they act as coreceptors. To
      characterize the early signals transmitted by CD4 and CD8, both CD4 and CD8 alpha
      were expressed in the same murine T cell hybridoma. In the double positive
      transfectants, CD4 and CD8 associated with equal amounts of p56lck (Lck), and
      both molecules enhanced interleukin 2 (IL-2) production equivalently when cross
      linked with suboptimal levels of anti-TCR antibody. However, in an in vitro
      kinase assay, cross-linking CD4 initiated fourfold greater kinase activity
      compared with CD8 cross-linking. In the same assay, when CD4 or CD8 was cross
      linked to the TCR, novel phosphorylated proteins were found associated with the
      TCR/CD4 complex but not with the TCR/CD8 complex. Consistent with this data,
      antiphosphotyrosine immunoblotting revealed greater tyrosine phosphorylation of
      intracellular substrates after TCR/CD4 cross-linking compared with TCR/CD8 cross
      linking. Additionally, a specific protein kinase C inhibitor (RO318220) inhibited
      CD8-mediated enhancement of IL-2 production far more effectively than CD4
      mediated enhancement. Thus, it appears that CD8 alpha may depend more on a
      protein kinase C-mediated signaling pathway, whereas CD4 may rely on greater
      tyrosine kinase activation. Such differential signaling via CD4 and CD8 has
      implications for thymic ontogeny and T cell activation.

PMID- 8294880
TI  - Suppression of human alpha-globin gene expression mediated by the recombinant
      adeno-associated virus 2-based antisense vectors.
AB  - We sought to investigate the usefulness of the adeno-associated virus 2 (AAV)
      based vectors to suppress the excess production of the human alpha-globin gene
      product towards developing a treatment modality for beta-thalassemia since
      accumulation of free alpha-globin reduces the lifespan of red blood cells in
      these patients. We constructed recombinant AAV virions containing the human alpha
      globin gene sequences in antisense orientation driven by the herpesvirus
      thymidine kinase (TK) promoter, the SV40 early gene promoter, and the human alpha
      globin gene promoter, respectively, as well as a bacterial gene for resistance to
      neomycin (neoR) as a selectable marker. These recombinant virions were used to
      infect a human erythroleukemia cell line (K562) that express high levels of alpha
      globin mRNA. Clonal populations of neoR cells were obtained after selection with
      the drug G418, a neomycin analogue. Total genomic DNA samples isolated from these
      cells were analyzed on Southern blots to document stable integration of the
      transduced neo and alpha-globin genes. Total cellular RNA samples isolated from
      mock-infected and recombinant virus-infected cultures were also analyzed by
      Northern blots. Whereas the TK promoter-driven antisense alpha-globin sequences
      showed no inhibition of expression of the endogenous alpha-globin gene, the SV40
      promoter and the alpha-globin gene promoter-driven antisense alpha-globin
      sequences suppressed the expression of this constitutively over-expressed gene by
      approximately 29 and 91%, respectively, at the transcriptional level. These
      studies suggest the feasibility of utilizing the AAV-based antisense gene
      transfer approach in the potential treatment of beta-thalassemia.

PMID- 8294881
TI  - The type II "receptor" as a decoy target for interleukin 1 in polymorphonuclear
      leukocytes: characterization of induction by dexamethasone and ligand binding
      properties of the released decoy receptor.
AB  - Whereas the signaling function of the interleukin 1 (IL-1) receptor type I (IL-1R
      I) has been well documented, the type II "receptor" has been suggested to act as
      a decoy target for this cytokine. Since IL-1 may represent a key target of the
      immunomodulatory and antiinflammatory properties of glucocorticoids (GC), the aim
      of this study was to investigate the effects of dexamethasone (Dex) on IL-1R
      expression in human polymorphonuclear leukocytes (PMN), which express
      predominantly the type II molecule (IL-1R II). We found that Dex augments the
      levels of steady state transcripts encoding the IL-1R I and, most prominently,
      those of IL-1R II. Dex induced both transcripts via transcription-dependent
      mechanisms and by prolongation of the mRNAs half-lives. Inhibition of protein
      synthesis superinduced basal and Dex-augmented IL-1R II mRNA, whereas it
      completely inhibited the induction by Dex of IL-1R I transcripts. Induction of IL
      1R II mRNA by Dex was associated with augmented membrane expression and release
      of the type II IL-1 binding molecule. This effect was mediated by the GC
      receptor. Other steroids (17 beta-estradiol, progesterone, and testosterone) were
      ineffective. The concentrations of IL-1 alpha and IL-1 receptor antagonist
      required to displace the binding of IL-1 beta to the soluble form of the decoy
      molecule induced by Dex from PMN were, respectively, 100 and 2 times higher
      compared with IL-1 beta. The induction by Dex of the type II receptor, a decoy
      molecule for IL-1, may contribute to the immunosuppressive and antiinflammatory
      activities of Dex.

PMID- 8294882
TI  - Expression of functional high affinity immunoglobulin E receptors (Fc epsilon RI)
      on monocytes of atopic individuals.
AB  - Suggestive evidence indicates that immunoglobulin E (IgE)-dependent activation of
      mononuclear phagocytes plays an important pathogenic role in allergic tissue
      inflammation. Prevailing opinion holds that low affinity IgE receptors are the
      relevant IgE-binding structures on monocytes/macrophages and that functional
      events occurring after cross-linking of membrane-bound IgE on these cells are
      mediated by these receptors. Here we demonstrate that peripheral blood monocytes
      can bind monomeric IgE via the high affinity IgE receptor (Fc epsilon RI) and
      that Fc epsilon RI expression on these cells is upregulated in atopic persons.
      Further, we demonstrate that, upon monocyte adherence to substrate, bridging of
      monocyte Fc epsilon RI is followed by cell activation. We propose that direct
      interaction of multivalent allergen with Fc epsilon RI(+)-bound IgE on
      mononuclear phagocytes results in cell signaling via Fc epsilon RI and that the
      biological consequences of this event may critically influence the outcome of
      allergic reactions.

PMID- 8294883
TI  - Human interleukin 10 induces naive surface immunoglobulin D+ (sIgD+) B cells to
      secrete IgG1 and IgG3.
AB  - During antigen-induced immune responses, human B cells switch isotype from
      immunoglobulin M (IgM)-IgD to IgG1-4, IgA1-2, or IgE. In the human, no cytokines
      have yet been demonstrated to act as switch factors for IgG1, IgG2, and IgG3. In
      this paper, we report that in response to interleukin 10 (IL-10), anti-CD40
      activated tonsillar surface IgD+ (sIgD+) B cells are induced to secrete large
      amounts of IgM, IgG1, and IgG3 but neither IgG2 nor IgG4. Cord blood purified B
      cells and lymphocytes from Hyper-IgM patients also produced IgG1 and IgG3 after
      culture with anti-CD40 and IL-10. In contrast, sIgD- isotype-committed B cells
      produce IgG1, IgG2, and IgG3 when activated through CD40 in the presence of IL
      10. Thus, in addition to its growth-promoting and differentiating activities on
      human B cells, IL-10 may represent a switch factor for IgG1 and IgG3.

PMID- 8294884
TI  - Distinct structural compartmentalization of the signal transducing functions of
      major histocompatibility complex class II (Ia) molecules.
AB  - Class II major histocompatibility complex encoded proteins (MHC class II or Ia
      molecules) are principal plasma membrane proteins involved in activation of both
      B and T cells during antigen-driven immune responses. Recent data indicate that
      class II molecules are more than simply recognition elements that provide a
      ligand for the T cell antigen receptor. Changes in B cell physiology that follow
      class II binding are now recognized as being required not only for the induction
      of T cell activation, but also for B cell activation and proliferation. It is
      interesting to note that class II molecules appear to transduce signals via two
      distinct mechanisms depending upon the differentiative state of the B cell on
      which they are expressed. While one of these pathways, involving cAMP generation
      and protein kinase C localization in the cytoskeletal/nuclear compartment, is
      seen in resting B cells, the second is seen in primed B cells and involves
      tyrosine kinase activation, inositol lipid hydrolysis, and Ca2+ mobilization. Use
      of this pathway is correlated with ability of class II to transduce signals
      leading to B cell proliferation. To begin to address the molecular basis of this
      unique, activation-dependent, differential coupling of class II to signaling
      pathways, we conducted mutational analysis of class II structural requirements
      for signal transduction. Here we report that the cytoplasmic (Cy) domains of I-Ak
      class II molecules are not required for either receptor-mediated activation of
      protein tyrosine phosphorylation or Ca2+ mobilization. This is in contrast to the
      requirement of the Cy domain of beta chain of class II for the alternate
      signaling pathway and efficient antigen presentation to autoreactive T cell
      lines. Disparate distribution of functional motifs within the MHC class II
      molecules may reflect use of distinct receptor associated effector molecules to
      sustain different modes of signal transduction in various class II-expressing
      cells.

PMID- 8294885
TI  - Susceptibility to cytotoxic T lymphocyte-induced apoptosis is a function of the
      proliferative status of the target.
AB  - Cytotoxic T lymphocytes (CTL) kill cells by perturbing the target's plasma
      membrane and by inducing the disintegration of the target cell's DNA into
      oligonucleosomal fragments, a process characteristic of apoptosis. We show that
      the DNA fragmentation event is distinct from the membrane lysis event and is
      dependent on the state of target cell activation or commitment into the mitotic
      cycle. Quiescent cells were refractory to DNA fragmentation, but not to membrane
      lysis. Log phase growth, transformation with c-myc, or infection of quiescent G0
      targets with herpes simplex virus-1, which induces a competent state for DNA
      synthesis, all enhanced target cell susceptibility to CTL-induced DNA
      fragmentation without altering the membrane lysis. These results suggest that G0
      cells are resistant to CTL-induced apoptosis, but that entry into G1 or a G1-like
      state by growth factors, cellular transformation, or DNA virus infection renders
      them competent to enter the apoptotic pathway(s).

PMID- 8294886
TI  - Recognizing depth-rotated objects: evidence and conditions for three-dimensional
      viewpoint invariance.
AB  - Five experiments on the effects of changes of depth orientation on (a) priming
      the naming of briefly flashed familiar objects, (b) matching individual sample
      volumes (geons), and (c) classifying unfamiliar objects (that could readily be
      decomposed into an arrangement of distinctive geons) all revealed immediate
      (i.e., not requiring practice) depth invariance. The results can be understood in
      terms of 3 conditions derived from a model of object recognition (I. Biederman,
      1987; J. E. Hummel & I. Biederman, 1992) that have to be satisfied for immediate
      depth invariance: (a) that the stimuli be capable of activating viewpoint
      invariant (e.g., geon) structural descriptions (GSDs), (b) that the GSDs be
      distinctive (different) for each stimulus, and (c) that the same GSD be activated
      in original and tested views. The stimuli used in several recent experiments
      documenting extraordinary viewpoint dependence violated these conditions.

PMID- 8294887
TI  - Perceptual and cognitive factors governing performance in comparative arrival
      time judgments.
AB  - Four experiments were conducted to investigate factors affecting relative arrival
      time judgments in the transverse plane. Across experiments, results indicated an
      overreliance on relative distance information. The levels of relative velocity
      and distance used in the arrival-time task were proved discriminable, and
      performance in both relative velocity and distance judgments predicted
      performance in the relative arrival-time task. Despite the distance bias, an
      attempt to integrate relative velocity and distance information was also
      evidenced. The distance bias appears to have resulted from resource limitations
      on the concurrent processing of relative velocity and distance information,
      causing relative velocity information to become resource limited. The final
      experiment assessed the stability of performance in each of the tasks over time
      and provided evidence of individual differences in the ability to coordinate
      information from multiple sources.

PMID- 8294888
TI  - Cerebral dominance and asynchrony between bimanual two-dimensional movements.
AB  - The asynchrony of bimanual movements was investigated. Right- and left-handers
      traced simple geometrical patterns (ellipses) continuously with both hands. All
      combinations of the direction of rotation in each hand were executed at different
      rhythms. Geometrically, performances were largely independent of manual
      dominance. However, by comparing the passage times at homologous positions, the
      authors found that the dominant hand led the nondominant one by about 25 ms. The
      asynchrony was affected by neither movement type nor rhythm. The variability of
      the asynchrony varied along the trajectory, with well-defined maxima and minima.
      The variability profiles for movements that engaged homologous muscles differed
      markedly from those that engaged nonhomologous muscles. The authors discuss the
      hypothesis that bimanual periodic movements are timed by a lateralized functional
      module and asynchrony is due to the necessity of transmitting time-keeping
      information to the other hemisphere.

PMID- 8294889
TI  - Aging and the inhibition of spatial location.
AB  - Two experiments compared the performance of older and younger adults on a task
      assessing suppression (or negative priming) for location of distractors. A 3rd
      experiment compared the 2 age groups on suppression for location and identity of
      distractors such that location was irrelevant to selection and response. Older
      and younger adults showed location suppression across all experiments. In
      Experiment 3, identity suppression was found for younger but not older adults. In
      addition, younger adults revealed an additive effect for suppression of identity
      and location. Consistent evidence of inhibition of return was not found for
      either age group. The findings are discussed in terms of the Hasher and Zacks
      (1988) theory of reduced inhibitory efficiency in the elderly and in terms of
      neurophysiological evidence that inhibition of identity and location may function
      separately within the 2 cortical visual systems.

PMID- 8294890
TI  - Visual offsets facilitate saccadic latency: does predisengagement of visuospatial
      attention mediate this gap effect?
AB  - Saccadic reaction time (RT) is reduced when a fixation stimulus is extinguished
      200 ms before a target appears. An attentional predisengagement theory (APT) may
      explain this gap effect: When covert attention is engaged (e.g., on fixation),
      the saccadic system is inhibited and RT is delayed; when the attended stimulus is
      extinguished, attention is disengaged, the inhibition is removed, and RT is
      facilitated. In 3 experiments covert attention was endogenously or exogenously
      cued to an object on the vertical meridian. Onset of a saccadic target on the
      horizontal meridian could be preceded by the offset of an attended or unattended
      object. Contrary to APT, RTs were identical after attended and unattended
      offsets. Results suggest that the gap effect has 2 components, and covert visual
      attention plays no role. One component is motor system preparation; the other is
      a fixation offset effect specific to the oculomotor system.

PMID- 8294891
TI  - Effect of gravitational cues on visual search for orientation.
AB  - To determine whether nonvisual (vestibular and somatosensory) information
      participates in low-level orientation processing, subjects in different postural
      conditions (upright, supine, and sitting immobilized) searched for a target
      distinguishable from distractors by difference in orientation (A. Treisman's,
      1985, "pop-out" paradigm). Searches for vertical and horizontal targets were
      dramatically modified as a function of the postural position, indicating that the
      processing of orientation in early vision is not only retinal but integrates
      information from the sensory graviceptors. This visuovestibular phenomenon is
      interpreted in the conceptual framework of D. H. Foster and P. A. Ward's (1991a)
      model based on local orthogonal orientation filters and T. A. Stoffregen and G.
      E. Riccio's (1988) dynamics of balance theory.

PMID- 8294892
TI  - Motor coactivation revealed by response force in divided and focused attention.
AB  - Four experiments examined effects of bimodal stimulation on response force (RF)
      in addition to reaction time (RT). In a divided-attention task (Experiments 1 to
      3), subjects were asked for a speeded response to either a visual or an auditory
      signal. In unimodal signal trials, either a visual or an auditory signal was
      presented alone, and in redundant-signals trials, both signals were presented
      simultaneously. The same stimulus arrangement was used in a focused-attention
      task (Experiment 4), but subjects had to withhold their response when an auditory
      signal was presented alone. In all experiments, the fastest RTs were attained in
      redundant-signals trials. In addition, RF was largest in redundant-signals
      trials, especially in the divided-attention task, suggesting a motor coactivation
      hypothesis. The results indicate that the type of stimulation influences not only
      when a response is initiated but also how the response is executed. This finding
      challenges the view, commonly held in mental chronometry, that late motoric
      processes remain untouched by experimental manipulations. A detailed analysis of
      the relationship between RT and RF revealed that these variables are not
      inherently redundant measures, and, therefore, RF recording may supplement the
      traditional RT measurement in mental chronometry.

PMID- 8294893
TI  - The locus of dual-task interference: psychological refractory effects on movement
      related brain potentials.
AB  - We sought to measure separately the motor potentials for each of 2 concurrent
      tasks and to use these measurements to identify the locus of dual-task
      interference. Lateralized readiness potentials (LRPs) were measured in the
      psychological refractory period paradigm, in which a separate response is
      required to each of 2 successive signals. As the interval between the signals
      decreased, the 2 reaction time (RT) tasks increasingly overlapped and the 2nd RT
      was prolonged. The LRP for the 2nd task was also delayed but maintained a
      constant temporal relation with the 2nd RT and sometimes preceded the 1st-task
      RT. The results indicate that (a) independent measures of the LRP can be obtained
      for each of 2 concurrent tasks, (b) slowing of the 2nd task was caused by a delay
      in processes that precede LRP onset, and (c) the 1st task may cease to interfere
      with the 2nd considerably before producing an overt response.

PMID- 8294894
TI  - Imagery-perception interaction depends on the shape of the image: a reply to
      Farah (1989).
AB  - Farah (1989) reported that point threshold stimuli are detected better if they
      appear at spatial locations in the visual field that are covered by an image. By
      replicating her experiment with 3 instead of the original 2 images, we found that
      the effect depends on the shape of the mentally projected image. A second
      experiment with 9 different shapes revealed that the effect is modulated by the
      compactness and the size of the image--it is enhanced with increasing compactness
      and attenuated with increasing size. These findings do not unequivocally support
      the idea that imagery and perception interact because both processes share the
      same representational medium. Rather, they suggest that imagery can cause a
      figure-ground segregation in the visual field and that the shape of the figure
      may determine the amount of attention that is allocated to different sections in
      the visual field.

PMID- 8294895
TI  - Psychobiology of Parkinson's Disease. Proceedings of a meeting. December 1993.

PMID- 8294896
TI  - MDL 72,974A: a selective MAO-B inhibitor with potential for treatment of
      Parkinson's disease.
AB  - MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine, hydrochloride] was
      designed to be a selective, mechanism-based irreversible inhibitor of monoamine
      oxidase type B (MAO-B). The compound is a potent, selective MAO-B inhibitor in
      vitro and in vivo. In vitro studies revealed an IC50 value (MAO-B) of 3.6 nM with
      189-fold selectivity compared to MAO-A. In rats, profound inhibition of MAO-B was
      achieved after a single oral dose with an ED50 of 0.18 mg/kg; a dose 44 times
      this amount was required to inhibit MAO-A by 50%. Selectivity was maintained
      following chronic dosing. MDL 72,974A had minimal sympathomimetic effects and did
      not potentiate the cardiovascular effects of tyramine, even at 50 times the MAO-B
      inhibiting dose. This inhibitor was equally effective and well-tolerated in man.
      In human volunteers, potent inhibition of platelet MAO-B activity was observed at
      submilligram doses (ED50 = 90 micrograms) following a single oral dose. Upon
      multiple oral doses of 100 micrograms, as much as 80% of MAO-B could be
      inhibited. In phase II studies, MDL 72,974A is proving to be a useful adjunct to
      conventional therapy. Patients (250) with Parkinson's disease, treated once daily
      with either 1 or 4 mg, together with L-Dopa and a decarboxylase inhibitor
      (MadoparR or SinemetR), saw significant improvements in symptoms compared with
      those on standard therapy without the inhibitor.

PMID- 8294897
TI  - Diminished subcortical nuclei volumes in Parkinson's disease by MR imaging.
AB  - Parkinson's disease (PD) is associated with changes in the substantia nigra,
      which communicates with subcortical nuclei. This study investigates subcortical
      nuclei volume in PD in vivo by magnetic resonance (MR) imaging. Caudate,
      putaminal, and thalamic nuclei were measured on axial MR images using a point
      counting method and systematic sampling. PD patients (n = 21) had significantly
      smaller subcortical nuclei than age- and sex-matched controls (p < 0.001) and
      depressed patients (p < 0.01). The decline in PD was not correlated with age,
      sex, or cortical volume. Depressed patients had significantly smaller caudate and
      putaminal nuclei than controls (p < 0.05 and 0.01, respectively) but thalamic
      nuclei were not significantly different. Caudate, putaminal, and thalamic nuclei
      volumes of controls were significantly negatively correlated with age (r = -0.58,
      p < 0.01; r = -0.77, p < 0.001; r = -0.57, p < 0.01, respectively). Depressed
      subjects demonstrated a negative trend. Volumetric measurements by MR imaging may
      be a useful in investigating the role of the basal ganglia in neurological
      disorders.

PMID- 8294898
TI  - Presymptomatic detection of Parkinson's disease.
AB  - Presymptomatic detection of Parkinson's disease is necessary if neuroprotective
      therapies are to be utilized in its treatment. Various methods (PET,
      electrophysiology, enzyme assays, olfactory function) may be applicable but none
      has been rigorously evaluated. Other possible approaches are now considered.
      Plasma HVA levels (pHVA) in the presence of debrisoquine may reflect cerebral
      dopamine function. However, there are no detectable differences in pHVA between
      newly diagnosed and untreated parkinsonian patients and control subjects.
      Compensatory increases in dopamine turnover may mask a decrease in pHVA in the
      early stages of the disease. So, at present this technique could not be used as a
      diagnostic tool. Post-mortem studies of brain in Parkinson's disease may provide
      clues to biochemical markers indicative of nigral pathology. Mitochondrial
      complex I activity is reduced in substantia nigra in Parkinson's disease and it
      was reported also to be markedly reduced in blood platelets. However, subsequent
      studies suggest that the difference in platelet complex I activity is too small
      to be diagnostic of Parkinson's disease. There are also selective reductions in
      brain glutathione levels in Parkinson's disease restricted to substantia nigra,
      which do not occur in other neurodegenerative disorders and are not due to drug
      treatment. Importantly, in incidental Lewy body disease (preclinical Parkinson's
      disease) nigral glutathione levels are reduced to the same degree as in advanced
      Parkinson's disease. So, some peripheral index of altered glutathione function
      may be valuable in the early detection of the disease process.

PMID- 8294899
TI  - Effects of dopaminergic drugs on superoxide dismutase: implications for
      senescence.
AB  - Both (-)-deprenyl and pergolide have been found to induce superoxide dismutase
      (SOD) in rat striata. There are several reports showing that strains or species
      with higher levels of SOD live longer. Other studies indicate that (-)-deprenyl
      can increase life expectancy in rats and that both (-)-deprenyl and pergolide may
      retard nigrostriatal degeneration. This present paper suggests that all these
      findings are linked, and that (-)-deprenyl and pergolide possess neuroprotective
      properties by virtue of an activated removal of toxic oxygen radicals.

PMID- 8294900
TI  - Use of an electrode selective for 1-methyl-4-phenylpyridinium (MPP+) to measure
      its uptake and accumulation by mitochondria.
AB  - An ion-selective electrode specific for the 1-methyl-4-phenylpyridinium ion
      (MPP+) was developed which allowed the measurement of the initial rate of uptake
      and the extent of accumulation of MPP+ by rat liver mitochondria. Using this
      electrode we demonstrated that the initial rate of uptake of MPP+ was not
      saturable and that the distribution of MPP+ across the mitochondrial inner
      membrane did not equilibrate with the membrane potential, in contrast to other
      lipophilic cations such as the methyltriphenyl phosphonium ion (TPMP+).
      Furthermore, incubation of mitochondria respiring on succinate with MPP+
      decreases the membrane potential. The possibility that the interaction of MPP+
      with mitochondria may be more complex than accumulation followed by inhibition of
      site 1, suggested by these and other data, is discussed.

PMID- 8294901
TI  - The role of iron in senescence of dopaminergic neurons in Parkinson's disease.
AB  - In Parkinson's disease (PD) an elevation of iron with staging of the disease has
      been observed in the substantia nigra (SN), especially the zona compacta (ZC).
      The iron is found to be present in glia, active microglia, macrophages,
      oligodendrocytes, outside the degenerated dopamine neurons and as a mild halo
      around Lewy bodies and within melanized dopamine neurons of SNZC. Although in
      control brains iron is absent in melanized dopamine neurons, in PD it is bound to
      neuromelanin in a fashion similar to the interaction of iron with synthetic
      dopamine-melanin. The iron in SNZC is thought to induce oxidative stress and thus
      be associated with the reported decreases of glutathione peroxidase activity,
      reduced glutathione (GSH), mitochondrial Complex I activity, calcium binding
      protein and increase of basal lipid peroxidation. An animal (rat) model of PD has
      been described in which intranigral iron injection induces a relatively specific
      lesioning of dopamine neurons resulting in behavioural and biochemical
      Parkinsonism in rats. Support for the neurotoxicity of iron liberated from an
      endogenous source has come from the 6-hydroxydopamine model of PD. This
      neurotoxin is thought to owe its toxicity to the liberation of iron from
      ferritin, which in turn alters the homeostasis of mitochondrial Ca2+ with the
      subsequent depletion of tissue GSH, resulting in oxidative stress. Pretreatment
      of rats with intraventricular injection of a relatively selective prototype iron
      chelator, desferrioxamine (desferal), attenuates the 6-hydroxydopamine lesion of
      nigrostriatal dopamine. Thus iron can fulfill the role of a neurotoxin. However
      it remains to be established whether its role in PD is primary or secondary to
      some other neurotoxic event.

PMID- 8294903
TI  - Die Pathoklise [Parkinson's disease].
AB  - The history of the concept of selective vulnerability of the basal ganglia with
      particular respect to the substantia nigra is briefly reviewed. During the past
      century attention has gradually focussed down from gross lesions of the basal
      ganglia through cell morphometry and presently to the level of the intracellular
      neurobiology. Despite an abundance of reported morphological and neurochemical
      changes it remains unresolved whether these findings indicate primary
      aetiological factors or secondary consequences of nigral cell death. In this
      debate, while MPTP has proven to be a most amenable model for the study of
      secondary parkinsonism it has not resolved the dilemma; equally uncertain are the
      claims derived from the MPTP hypothesis of nigral vulnerability that selective
      MAO inhibition has a protective effect on the natural history of Parkinson's
      disease. Some of the evidence, past and present, will be reviewed in so far that
      it reflects upon the concept of pathoclisis and the selective vulnerability of
      nigral cells and recent evidence from clinical trials and from the study of human
      foetal nigral cells in tissue culture will be presented.

PMID- 8294902
TI  - The pharmacological basis of the beneficial effects of (-)deprenyl (selegiline)
      in Parkinson's and Alzheimer's diseases.
AB  - (-)Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), structurally closely related
      to phenylethylamine (PEA), is a drug with a unique pharmacological spectrum. It
      is a highly potent and selective irreversible inhibitor of B-type monoamine
      oxidase (MAO) and interferes with the uptake of catecholamines and indirectly
      acting symphathomimetics. In striking contrast to PEA and its relatives, which
      displace the transmitter from the storage places, (-)deprenyl inhibits the
      releasing effect of tyramine and is up to the present the only safe MAO inhibitor
      which can be administered without dietary restrictions. Maintenance on (
      )deprenyl enhances selectively superoxide dismutase (SOD) and catalase activities
      in the striatum. This effect is unrelated to the MAO and uptake inhibitory
      effects of the drug. Maintenance on (-)deprenyl facilitates the activity of the
      nigrostriatal dopaminergic neurons with remarkable selectivity and this effect
      too, is unrelated to either the MAO or the uptake inhibitory effects of the drug.
      Maintenance on (-)deprenyl prevents the characteristic age-related morphological
      changes in the neuromelanin granules of the neurocytes in the substantia nigra.
      As a consequence of its complex spectrum of activity male rats maintained on (
      )deprenyl live longer, lose their capacity to ejaculate later, show improved
      performance in learning tests and maintain this activity for a longer period than
      their untreated peers. Patients with Parkinson's disease maintained on levodopa
      plus (-)deprenyl (10 mg daily) live significantly longer than those on levodopa
      alone. Freshly diagnosed patients treated with (-)deprenyl need levodopa later
      than their placebo-treated peers. Continuous administration of (-)deprenyl
      improves the performance of patients with Alzheimer's disease.

PMID- 8294904
TI  - Lesions of mouse striatum induced by 6-hydroxydopamine differentially alter the
      density, rate of synthesis, and level of gene expression of D1 and D2 dopamine
      receptors.
AB  - To study the effects of altering dopaminergic input on the levels and rate of
      synthesis of dopamine receptors, corpora striata of mice were lesioned
      unilaterally with 6-hydroxydopamine (6-OHDA), and the densities and levels of the
      mRNAs for D1 and D2 dopamine receptors were determined. The results showed that 6
      OHDA caused significant reductions in D1 dopamine receptors and in D1 dopamine
      receptor mRNA in dorsolateral and dorsomedial regions of the lesioned striatum.
      By contrast, 6-OHDA lesions caused significant increases in D2 dopamine receptors
      and in D2 dopamine receptor mRNA in dorsolateral and ventrolateral regions of the
      lesioned striatum. To assess the effects of 6-OHDA lesions on the rate of
      synthesis of D1 and D2 dopamine receptors, the irreversibly acting dopamine
      receptor antagonist 2-ethoxy-1-ethoxycarbonyl-1,2- dihydroquinoline (EEDQ) was
      administered, and the rate of recovery of these receptors determined. The lesions
      decreased the rate of synthesis of D1 dopamine receptors in dorsolateral striatum
      but increased the rate of synthesis of D2 dopamine receptors in dorsolateral
      striatum. Correlation of these molecular events with dopaminergic behaviors
      showed that the rate of recovery from EEDQ-induced cataleptic activity and the
      recovery from inhibition of quinpirole-induced rotational behavior was more rapid
      than the recovery of either the D1 or D2 dopamine receptor. These results suggest
      that dopaminergic denervation differentially affects the rate of synthesis of D1
      and D2 dopamine receptors in mouse striatum, and that these alterations in the
      rates of synthesis of the receptors may be explained by corresponding alterations
      in the levels of the respective transcripts for these receptors.

PMID- 8294905
TI  - Ontogeny of kainate-induced gene expression in rat hippocampus.
AB  - The ontogeny of kainate induction of AP-1 mRNAs, proteins, and DNA binding
      activities was examined in the rat hippocampus. In addition, kainate induction of
      preproenkephalin and preprodynorphin mRNAs was examined; these genes have been
      shown to be induced by kainate and have been suggested to be targets of AP-1
      regulation in adult rat hippocampus. Despite producing seizures at postnatal day
      (P) 7, kainate failed to induce AP-1 or opiate gene expression and did not
      increase AP-1 DNA binding activity at this age. Basal levels of AP-1 and opiate
      mRNAs were low in P7 hippocampus. Basal levels of c-jun protein and AP-1 DNA
      binding activity were elevated in the P7 hippocampus, to values greater than
      induced levels in adult hippocampus. Furthermore, AP-1 DNA binding in P7
      hippocampal nuclear extract was unaffected by antibodies against fos-related
      antigens, in contrast to hippocampal extracts from the older rats examined. At
      P14, induction of AP-1 and preproenkephalin (but not preprodynorphin) mRNAs was
      observed with kainate treatment, but the time course for inductions was delayed
      relative to kainate inductions in the adult hippocampus. At P21, responses to
      kainate were similar to the adult response. Unlike in adult hippocampus, seizure
      activity caused by kainate treatment does not increase the transcription factor
      and opioid peptide gene expression in the hippocampi of P7 rats.

PMID- 8294906
TI  - Characterization of an atypical member of the Na+/Cl(-)-dependent transporter
      family: chromosomal localization and distribution in GABAergic and glutamatergic
      neurons in the rat brain.
AB  - A 3.7-kb cDNA fragment, designated rat-XT1, was isolated from a rat whole-brain
      cDNA library. The nucleotide sequence of XT1 codes for a 727 amino acid protein
      with a calculated molecular mass of 81,139 Da and 12 putative transmembrane
      domains. This protein shares significant homology (28-32%) with the monoamine-
      (dopamine, norepinephrine, serotonin), amino acid- (taurine, proline, GABA,
      glycine), choline-, and betaine-, Na+/Cl(-)-dependent transporters. The homology
      is especially high within the first, second, sixth, and eighth transmembrane
      domains (45-75%). Thus, XT1 clearly belongs to the Na+/Cl(-)-dependent
      neurotransmitter transporter superfamily. However, XT1 may define a new subfamily
      of transporter because it differs structurally from other members of this family
      in that the extracellular loop linking transmembrane domains 7 and 8 and the C
      terminal tail are significantly larger in size. Transient or stable expression of
      rat-XT1 failed to confer to the transfected cells the ability to transport
      actively any of the > 60 established or putative neurotransmitter substances
      assessed. Northern blot analyses of peripheral and neural tissues demonstrated
      that expression of the 8-kb XT1 mRNA is essentially restricted to the nervous
      system. In situ hybridization demonstrated a broad but discrete localization of
      XT1 message in the CNS, particularly in the cerebellum (Purkinje and granular
      cell layers), the hippocampus (pyramidal and granular cell layers), and the
      thalamus and throughout the cerebral cortex. This distribution parallels that of
      the neurotransmitters glutamate and aspartate; however, neither of these
      excitatory amino acids is a substrate for transport. One noticeable exception to
      the codistribution of the mRNA for rat-XT1 and these excitatory neurotransmitters
      is the cerebellar Purkinje cell layer, in which GABAergic neurons are localized.
      The gene encoding for XT1 is localized to the mouse chromosome 3 in the vicinity
      of the locus for the mouse neurological disorder spastic (spa).

PMID- 8294907
TI  - The addition of glucose-1-phosphate to the cytoplasmic glycoprotein
      phosphoglucomutase is modulated by intracellular calcium in PC12 cells and rat
      cortical synaptosomes.
AB  - In a number of different cell types, phosphorylation of a 63-kDa protein has been
      shown to increase rapidly in response to stimuli that lead to an increase in
      intracellular calcium. Here, a stimulus-sensitive protein at this molecular
      weight is identified in PC12 cells and rat cortical synaptosomes as
      phosphoglucomutase. In addition, the added phosphate is shown to be in an
      oligosaccharide terminating in phosphodiester-linked glucose. In synaptosomes,
      incorporated radioactivity, following incubation with [14C]glucose or the [beta
      35S]phosphorothioate analogue of UDP-glucose, was found to increase within 5 s of
      stimulation and return to baseline within 25 s. Despite the many pathways
      utilizing glucose, this was the only detectable protein glycosylation observed in
      synaptosomes. These results indicate that cytoplasmic glycosylation is reversible
      and rapidly regulated, and suggest that phosphoglucomutase undergoes an
      alteration in function and/or topography in response to increases in
      intracellular calcium.

PMID- 8294908
TI  - Calcium-independent release of acetylcholine from stable cell lines expressing
      mouse choline acetyltransferase cDNA.
AB  - Stably transfected cells expressing mouse choline acetyltransferase (ChAT) cDNA
      were established, and the synthesis and release of acetylcholine (ACh) were
      examined. A cDNA clone coding for mouse ChAT was inserted into an expression
      vector (pEF321) containing a promoter for human elongation factor 1 alpha to
      construct pEFmChAT. Neuronal (NG108-15, NS20Y, N1E115, and Neuro2A) and
      nonneuronal cell lines (L cells and NIH3T3) were transfected with pEFmChAT, and
      the cell lines that stably expressed high ChAT activity were selected. These
      cells expressed the 66-kDa ChAT protein and accumulated ACh mostly in the
      cytosol. The concentration of intracellular ACh in the cells increased upon
      raising the choline level in the medium. The cells continuously released ACh in a
      Ca(2+)-independent fashion. Neither high K+ nor calcium ionophore stimulated
      release of ACh from the cells.

PMID- 8294909
TI  - Production and characterization of recombinant rat brain-derived neurotrophic
      factor and neurotrophin-3 from insect cells.
AB  - Rat brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) were
      engineered for expression in a baculovirus-infected Spodoptera frugiperda insect
      cell system. The BDNF and NT-3 from the culture supernatants were purified by ion
      exchange and reverse-phase chromatography to apparent homogeneity. The
      purification procedure yielded approximately 2 mg of pure rat BDNF or NT-3 per
      liter of culture supernatant. A single N-terminus only was found for either
      secreted molecule and was analogous to that predicted from the corresponding cDNA
      sequence. The recombinant neurotrophins obtained were also homogeneous with
      regard to molecular weight and amino acid sequence. In their native conformation,
      the insect cell-produced rat BDNF and NT-3 molecules were homodimers consisting
      of 119 amino acid polypeptide chains. Thus, although the genes transfected into
      the S. frugiperda cells coded for proBDNF or proNT-3, the BDNF and NT-3 recovered
      after purification were > 95% fully processed, mature protein. Mature recombinant
      rat BDNF and NT-3 were found not to be significantly glycosylated. Pure,
      recombinant rat BDNF and NT-3 promoted the survival of embryonic dorsal root
      ganglion neurons in the low picomolar range. Because recombinant rat BDNF and NT
      3 can be obtained in large quantities, purified to near homogeneity, and are
      identical in amino acid sequence to the corresponding human proteins, they are
      suitable for evaluation in animal models.

PMID- 8294910
TI  - Protein kinase inhibitor H-7 differentially affects early and delayed nerve
      growth factor responses in PC12 cells.
AB  - The effects of the protein kinase inhibitor H-7 on early and delayed responses to
      nerve growth factor (NGF) were investigated in PC12 cells. H-7 reduced the NGF
      induced expression of c-Fos in a dose-dependent manner without affecting the time
      course of c-Fos appearance. Conversely, H-7 potentiated delayed NGF effects,
      i.e., neurite outgrowth and Ca2+/phospholipid-dependent protein kinase (PKC)
      induction, but not choline acetyltransferase induction. Long-term treatment with
      NGF resulted in an increase of at least four tyrosine-phosphorylated protein
      bands with molecular masses between 39 and 48 kDa, which was also potentiated by
      H-7. In the absence of NGF, H-7 had no significant effect on c-Fos expression,
      tyrosine phosphorylation of the 45 kDa protein, or choline acetyltransferase
      activity. However, 4 days of exposure to H-7 alone induced PKC activity and
      tyrosine phosphorylation of the 39-kDa protein. The action of H-7 derivatives on
      neurite outgrowth did not correlate with their inhibition profile of cyclic
      nucleotide-dependent protein kinases. Down-regulation of PKC activity by
      prolonged exposure to phorbol ester did not completely abolish the effects of NGF
      and H-7 on induction of c-Fos, choline acetyltransferase activity, and neurite
      outgrowth, indicating that PKC-independent pathways contribute to these actions.
      These results suggest that additional pathway(s) sensitive to H-7 may exist,
      which induce immediate early gene expression and suppress neuronal
      differentiation of PC12 cells.

PMID- 8294911
TI  - Stimulation of the cyclic GMP pathway by NO induces expression of the immediate
      early genes c-fos and junB in PC12 cells.
AB  - Stimulation of several second messenger pathways induces the expression of
      immediate early genes such as c-fos, c-jun, junB, and junD, but little is known
      about their induction via the stimulation of the cyclic GMP pathway. Here we
      looked at the expression of early genes in pheochromocytoma PC12 cells after
      activation of cytosolic guanylate cyclase by sodium nitroprusside. This compound
      spontaneously releases NO, a molecule known to be involved in cell communication.
      We found that expression of c-fos and junB but not of c-jun or junD is increased
      upon activation of cyclic GMP pathway. c-fos mRNA expression was the most
      activated (fourfold at 30 min), whereas junB response was more modest (2.2-fold
      activation at 60 min). Nuclear extracts of stimulated cells show increased
      binding capacity to the AP1 binding site consistent with the dose-response curve.
      The activating effect of nitroprusside could be reproduced by dipyridamole, a
      selective cyclic GMP phosphodiesterase inhibitor and by 8-p-chlorophenylthio
      cyclic GMP, a permeant selective cyclic GMP-dependent protein kinase activator,
      and abolished by KT5823, an inhibitor of that kinase. The results show that NO
      promotes early gene activation and AP1 binding enhancement through the
      stimulation of the cyclic GMP pathway.

PMID- 8294912
TI  - Age-associated changes of rat brain neuronal and astroglial poly(ADP-ribose)
      polymerase activity.
AB  - Nuclear poly(ADP-ribose) polymerase levels as well as the DNA strand break levels
      of whole-brain neuronal and astroglial cells were investigated. Three- and 30
      month-old rats were used. Low-molecular-weight neurofilaments and glutamine
      synthetase served as neuronal and astroglial markers, respectively. A large
      increase in the poly(ADP-ribose) polymerase activity was observed in the neurons
      (threefold) and astrocytes (3.7-fold) derived from 30-month-old rats. Similarly,
      the amount of poly(ADP-ribose) polymerase, evaluated per milligram of DNA,
      increased approximately 3.5-fold in neurons and 3.9-fold in astrocytes prepared
      from 30-month-old rats. Whether the increase in the poly(ADP-ribose) polymerase
      activity was due to an enhanced rate of DNA strand break was investigated by
      determining the rate of DNA unwinding. A significant increase in DNA unwinding
      rate was detected in the neurons (2.7-fold), although a lower increase was
      observed in the astroglia (1.3-fold) of aged animals.

PMID- 8294913
TI  - Guinea pig histamine H1 receptor. I. Gene cloning, characterization, and tissue
      expression revealed by in situ hybridization.
AB  - An intronless DNA encoding the guinea pig H1 receptor was cloned from a genomic
      library using probes derived from the bovine H1 receptor. It encodes a protein of
      488 amino acids with a calculated molecular mass of 55,619 daltons compared with
      a size of 56-68 kDa for the photoaffinity-labeled receptor as determined by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The protein
      displays a 66% homology with the bovine receptor. Stable expression of the H1
      receptor, characterized by the appearance of [3H]mepyramine binding sites with a
      pharmacology similar to that of the native H1 receptor, was obtained following
      transfection of Chinese hamster ovary cells. Southern blot analysis, using a
      variety of restriction enzymes, did not provide any evidence of multiple H1
      isoreceptors. Northern blot analysis of a variety of guinea pig peripheral or
      cerebral tissues identified, in most cases, a single transcript of 3.3 kb, but
      also, in some tissues, a second transcript of 3.7 kb, possibly generated by the
      use of different promoter or polyadenylation sites or corresponding to a
      transcript from a distinct gene. In situ hybridization studies showed the highly
      contrasted cerebral expression of H1-receptor gene transcripts, which was
      compared with autoradiographic receptor localization. This allowed the
      identification of some major cell populations expressing the H1 receptor, e.g.,
      Purkinje cells in cerebellum or pyramidal cells in the hippocampal complex.

PMID- 8294914
TI  - Guinea pig histamine H1 receptor. II. Stable expression in Chinese hamster ovary
      cells reveals the interaction with three major signal transduction pathways.
AB  - A cDNA encoding a guinea pig histamine H1 receptor was stably expressed in
      Chinese hamster ovary (CHO) cells. In one resulting clone, named CHO(H1), the H1
      receptor was found to be coupled to several major signal transduction pathways.
      In each case the involvement of a Gi/Go protein with pertussis toxin (PTX) was
      assessed, as well as the influence of extracellular Ca2+ and of protein kinase C
      activation by phorbol 12-myristate 13-acetate (PMA). Histamine induced, in a PTX-
      and PMA-insensitive manner, a biphasic increase in the intracellular Ca2+ level
      of which only the second sustained phase was dependent on the extracellular Ca2+
      level. Histamine also caused a threefold elevation of inositol phosphate
      production, which was PTX-insensitive, but slightly inhibited by PMA and reduced
      by 75% in the absence of extracellular Ca2+. Histamine also caused a massive
      release of arachidonic acid, which occurred in a Ca(2+)- and PMA-sensitive
      manner, probably through the activation of a cytosolic phospholipase A2, which
      partly involves coupling to a PTX-sensitive G protein. In comparison, in HeLa
      cells endowed with a native H1 receptor, the histamine-induced arachidonic acid
      release was also Ca(2+)- and PMA-sensitive, but totally PTX-insensitive. Finally,
      in CHO(H1) cells, histamine in very low concentrations potentiated the cyclic AMP
      accumulation induced by forskolin. This response appeared to be insensitive to
      PTX, extracellular Ca2+, and PMA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294915
TI  - Characterization of serotonin transporter in goldfish retina by the binding of
      [3H]paroxetine and the uptake of [3H]serotonin: modulation by light.
AB  - The serotonin (5-HT) uptake system of goldfish retina was evaluated by the
      binding of [3H]paroxetine to membrane preparations and the uptake of [3H]5-HT
      into isolated cells from goldfish retina. The order of potency of inhibitors of
      [3H]paroxetine binding was imipramine > 5-methoxy-N,N- dimethyltryptamine >
      desipramine > fluoxetine > citalopram > 5-HT. The saturation experiments
      indicated a high-affinity binding site, and positive cooperativity with Hill
      coefficient higher than unity. The association reached equilibrium at about one
      hour of incubation and was efficiently displaced by imipramine. The equilibrium
      dissociation constants calculated by the antilog of the log concentration of
      ligand giving 50% of occupation, and by the ratio of dissociation/association
      constants, were similar: 5.84 and 2.34 nM, respectively. The binding was not
      significantly reduced by decreasing the temperature of incubation and was sodium
      dependent. The lesion with 5,7-dihydroxytryptamine reduced the binding to 60%.
      The uptake of [3H]5-HT into isolated cells also showed positive cooperativity.
      The order of potency of inhibitors was similar to the one obtained for the
      binding of [3H]paroxetine. Darkness increased the uptake of 5-HT. The allosteric
      regulation of the 5-HT transporter and the modulation by light could be related
      to the physiological role of the monoamine, as a neurotransmitter and as a
      precursor of melatonin synthesis in the retina.

PMID- 8294916
TI  - Heterogeneity of nucleotide receptors in NG108-15 neuroblastoma and C6 glioma
      cells for mediating phosphoinositide turnover.
AB  - We have compared the characteristics of receptors for nucleotide analogues and
      the involvement of phospholipase C (PLC) in the effector mechanism in NG108-15
      neuroblastoma and C6 glioma cells. The relative potency of these analogues to
      stimulate inositol phosphate (IP) formation is UTP > UDP >> 2-methylthio-ATP (2
      MeSATP), GTP > ATP, CTP > ADP > UMP in NG108-15 cells and ATP > UTP > ADP > GTP >
      UDP >> 2Me-SATP, CTP, UMP, in C6 glioma cells. alpha, beta-Methylene-ATP, beta,
      gamma-methylene-ATP, AMP, and adenosine had little or no effect in both types of
      cells. The EC50 values were 3 and 106 microM for UTP in NG108-15 and C6 glioma
      cells, respectively. The EC50 value for ATP in C6 glioma cells was 43 microM. 2
      MeSATP was threefold more potent than ATP in NG108-15 cells but had little effect
      in C6 glioma cells at 1 mM. In NCB-20 cells, a similar rank order of potency to
      that found in NG108-15 cells, i.e., UTP >> GTP > ATP > CTP, was observed. In both
      NG108-15 and C6 glioma cells, preincubation with ATP or UTP caused a pronounced
      cross-desensitization of subsequent nucleotide-stimulated IP production. ATP and
      UTP displayed no additivity in terms of IP formation at maximally effective
      concentrations. In contrast, endothelin-1, bradykinin, and NaF interacted in an
      additive manner with either nucleotide in stimulating PI hydrolysis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8294917
TI  - Visualizing dopamine and serotonin transporters in the human brain with the
      potent cocaine analogue [125I]RTI-55: in vitro binding and autoradiographic
      characterization.
AB  - The cocaine analogue RTI-55 was evaluated as a probe for in vitro labeling and
      localization of dopamine and serotonin transporters after death in the human
      brain. Kinetic, saturation, and competition binding experiments indicated complex
      interactions of the radioligand with the identification of multiple recognition
      sites. In membrane binding assays, the association of [125I]RTI-55 at 25 degrees
      C to putamen membranes was monophasic. In contrast, dissociation of [125I]RTI-55
      occurred in two phases with t1/2 values of 9.4 and 36.5 min, respectively.
      Saturation analysis of [125I]RTI-55 binding demonstrated two binding sites in the
      human putamen with KD values of 0.10 +/- 0.02 and 1.81 +/- 0.46 nM. The binding
      of [125I]RTI-55 was displaced by a wide range of cocaine analogues and monoamine
      uptake inhibitors. The rank order of potency demonstrated in competition assays
      with human putamen membranes indicates that the radioligand labels cocaine
      recognition sites on the dopamine transporter (mazindol > GBR 12909 > GBR 12935 >
      paroxetine > nisoxetine > desipramine > or = fluoxetine > citalopram). In the
      human occipital cortex, [125I]RTI-55 recognized multiple binding sites with KD
      values of 0.02 +/- 0.01 and 4.18 +/- 0.46 nM. The rank order of potency for
      inhibition of [125I]RTI-55 binding to cerebral cortex membranes (paroxetine >
      citalopram > GBR 12909 > or = mazindol > or = nisoxetine > benztropine) suggests
      that [125I]RTI-55 labels the serotonin transporter in the human occipital cortex.
      Autoradiographic mapping of [125I]RTI-55 revealed very high densities of cocaine
      recognition sites over areas known to be rich in dopaminergic innervation,
      including the caudate, putamen, and nucleus accumbens.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8294918
TI  - Muscarinic receptor-mediated increase in extracellular inositol 1,4,5
      trisphosphate levels in the rat hippocampus: an in vivo microdialysis study.
AB  - The extracellular concentration of inositol 1,4,5-trisphosphate (IP3) has been
      monitored in the ventral hippocampus of the anesthetized rat by using a
      microdialysis technique coupled to a radioreceptor assay. Three hours after the
      implantation of the cannula, basal extracellular concentration of IP3 (corrected
      for a 9% recovery) was 71 nM (0.39 pmol/60-microliters fraction) and remained
      stable for at least 5 h. Local infusion of carbachol for 60 min caused a
      significant concentration-related increase in extracellular IP3 levels (0, 24,
      and 57% at 1, 50, and 100 microM, respectively). Acetylcholine (100 microM) and
      muscarine (100 microM) increased IP3 outflow by 40 and 42%, respectively. The
      effect of carbachol was fully prevented by coinfusion of 10 microM pirenzepine
      and reduced by 1 microM tetrodotoxin indicating that the carbachol response is
      mediated by neuronal muscarinic receptors. These data demonstrate the feasibility
      of using microdialysis and a radioreceptor assay to measure IP3 in the
      extracellular space. This approach could prove useful for the study of the in
      vivo operation of muscarinic and, by extension, a number of receptors coupled to
      phosphoinositide turnover.

PMID- 8294919
TI  - Propentofylline and other adenosine transport inhibitors increase the efflux of
      adenosine following electrical or metabolic stimulation of rat hippocampal
      slices.
AB  - Propentofylline is a novel neuroprotective agent that has been shown to act as an
      adenosine transport inhibitor as well as an adenosine receptor antagonist. In the
      present series of experiments we have compared the effects of propentofylline
      with those of known adenosine transport inhibitors and receptor antagonists on
      the formation of adenosine in rat hippocampal slices. The ATP stores were labeled
      by incubating the slices with [3H]adenine. The total 3H overflow and the overflow
      of endogenous and 3H-labeled adenosine, inosine, and hypoxanthine were measured.
      Adenosine release, secondary to ATP breakdown, was induced both by
      hypoxia/hypoglycemia and by electrical field stimulation. Propentofylline (20-500
      microM) increased the release of endogenous and radiolabeled adenosine, without
      increasing the total release of purines. Thus, the drug altered the pattern of
      released purines, i.e., increasing adenosine and decreasing inosine and
      hypoxanthine. This pattern, which was observed when purine release was induced
      both by electrical field stimulation and by hypoxia/hypoglycemia, was shared by
      the nucleoside transport inhibitor dipyridamole (1 microM) and by mioflazine (1
      microM) and nitrobenzylthioinosine (1 microM). By contrast, other xanthines,
      including theophylline (100 microM) and 8-cyclopentyltheophylline (10 microM),
      enprofylline (100 microM), or torbafylline (300 microM), if anything, increased
      the total release of purines without alterations of the pattern of release. These
      results indicate that nucleoside transport inhibitors can decrease the release of
      purines from cells and at the same time increase the concentration of
      extracellular adenosine, possibly by preventing its uptake and subsequent
      metabolism. This change in purine metabolism may be beneficial with regard to
      cell damage after ischemia. The results also indicate that propentofylline
      behaves in such a potentially beneficial manner.

PMID- 8294920
TI  - Effects of chronic nicotine infusion on kinetics of high-affinity nicotine
      binding.
AB  - It is well established that chronic nicotine treatment produces a dose-dependent
      increase in high-affinity L-[3H]nicotine binding. This increase may be due to
      chronic desensitization of the receptor. Sophisticated kinetic analyses of high
      affinity nicotine binding to rat brain have demonstrated that the association
      rate is biphasic; the fast phase may represent binding to a high-affinity
      predesensitized state and the slow phase may represent binding to a lower
      affinity ground state that then isomerizes to form the high-affinity binding
      site. This isomerization presumably leads to receptor desensitization. The
      studies reported here assessed whether binding to mouse brain nicotinic receptors
      shows these same properties and whether chronic intravenous infusion of nicotine
      results in changes in these kinetic properties. The results obtained indicate
      that mouse brain nicotine binding also shows biphasic association kinetics and
      uniphasic dissociation kinetics, which supports the assertion that the receptor
      exists in two interconvertible states. However, unlike other results obtained
      with rat brain, the rate of the slow association process did not change with
      ligand concentration. Chronic infusion resulted in a dose-dependent increase in L
      [3H]nicotine binding, but the ratio of fast/slow phases of binding was not
      changed by these treatments. These results suggest that chronic infusion does not
      alter measurably the kinetics of nicotinic receptor binding when measured in
      vitro.

PMID- 8294921
TI  - Dopamine D1 and D2 receptors and their signal system present in coated vesicles
      prepared from bovine striatal tissue.
AB  - Coated vesicles (CVs) isolated from bovine striatal tissue were examined to
      determine whether they are associated with dopamine signal systems consisting of
      dopamine D1 and D2 receptors, G proteins, and adenylate cyclase. Dopamine
      receptors in CVs were characterized by a dopamine D1 receptor antagonist, [3H]SCH
      23390, and a dopamine D2 receptor antagonist, [3H]-spiroperidol. The bindings of
      both ligands were specifically saturable and reversible with a dissociation
      constant (KD) of 0.65 and 0.5 nM, respectively. Dopaminergic antagonists and
      agonists inhibited the specific bindings of [3H]SCH 23390 and [3H]spiroperidol in
      a stereoselective and concentration-dependent manner with an appropriate rank
      order potency for dopamine D1 or D2 receptors. The regulations of the agonist
      binding by guanyl-5-ylimidodiphosphate were observed. ADP ribosylation of the CVs
      with [32P]NAD demonstrated predominant labeling of bands of M(r) 47,000-52,000,
      42,000-45,000, and 40,000-39,000, which corresponded to the known molecular
      weights of the alpha subunits of Gs and Gi proteins. The presence of alpha and
      beta subunits of G proteins in the CVs was also confirmed by immunoblotting
      assay. Adenylate cyclase activity, which was stimulated by SKF 38393 and
      inhibited by dopamine D2 receptor agonists, was present in the CVs. These
      findings suggest that the dopamine D1 and D2 receptors in the CVs couple with
      adenylate cyclase via Gs/Gi protein.

PMID- 8294923
TI  - Zinc inhibition of t-[3H]butylbicycloorthobenzoate binding to the GABAA receptor
      complex.
AB  - The effect of Zn2+ on t-[3H]butylbicycloorthobenzoate ([3H]TBOB) binding to the
      GABAA receptor complex was studied autoradiographically in rat brain. Zn2+
      inhibited [3H]TBOB binding in a dose-dependent manner at physiological
      concentrations. Saturation analysis revealed noncompetitive inhibition in various
      brain regions. The inhibitory effect of Zn2+ had regional heterogeneity; regions
      showing the greatest inhibition of [3H]TBOB binding were cortical laminae I-III,
      most areas of hippocampus, striatum, septum, and cerebellar cortex. Regions with
      relatively less inhibition of [3H]TBOB binding included cortical laminae V-VI,
      thalamus, superior colliculus, inferior colliculus, and central gray matter. The
      effect of Zn2+ and those of other GABAA ligands, such as benzodiazepines,
      bicuculline, isoguvacine, and picrotoxin, on [3H]TBOB binding seemed to be
      additive. Ni2+, Cd2+, and Cu2+ also inhibited [3H]TBOB binding with a regional
      heterogeneity similar to that produced by Zn2+. These results are consistent with
      Zn2+ acting at the previously detected recognition site on the GABAA receptor
      complex, distinct from the picrotoxin, GABA, and benzodiazepine sites. The
      regional heterogeneity of the Zn2+ effect may reflect differential regional
      distribution of GABAA receptor subtypes among brain regions. Other divalent
      cations probably act at the Zn2+ binding site.

PMID- 8294922
TI  - Endothelin-1 receptor binding and cellular signal transduction in cultured human
      brain endothelial cells.
AB  - The kinetic properties of endothelin-1 (ET-1) binding sites and the production of
      inositol phosphates (IPs; IP1, IP2, IP3), cyclic AMP, thromboxane B2, and
      prostaglandin F2 alpha induced by various endothelins (ET-1, ET-2, ET-3, and
      sarafotoxin S6b) were examined in endothelial cells derived from human brain
      microvessels (HBECs). The presence of both high- and low-affinity binding sites
      for ET-1 with KD1 = 122 pM and KD2 = 31 nM, and Bmax1 = 124 fmol/mg of protein
      and Bmax2 = 909 fmol/mg of protein, respectively, was demonstrated on intact
      HBECs. ET-1 dose-dependently stimulated IP accumulation with EC50 (IP3) = 0.79
      nM, whereas ET-3 was ineffective. The order of potency for displacing ET-1 from
      high-affinity binding sites (ET-1 > ET-2 > sarafotoxin S6b > ET-3) correlated
      exponentially with the ability of respective ligands to induce IP3 formation. ET
      1-induced IP3 formation by HBEC was inhibited by the ETA receptor antagonist,
      BQ123. The protein kinase C activator phorbol myristate ester dose-dependently
      inhibited the ET-1-stimulated production of IPs, whereas pertussis toxin was
      ineffective. Cyclic AMP production by HBECs was enhanced by both phorbol
      myristate ester and ET-1, and potentiated by combined treatment with ET-1 and
      phorbol myristate ester. Data indicate that protein kinase C plays a role in
      regulating the ET-1-induced activation of phospholipase C, whereas interaction of
      different messenger systems may regulate ET-1-induced accumulation of cyclic AMP.
      ET-1 also stimulated endothelial prostaglandin F2 alpha production, suggesting
      that activation of phospholipase A2 is most likely secondary to IP3-mediated
      intracellular calcium mobilization because both ET-1-induced IP3 and
      prostaglandin F2 alpha were inhibited by BQ123. These findings are the first
      demonstration of ET-1 (ETA-type) receptors linked to phospholipase C and
      phospholipase A2 activation in HBECs.

PMID- 8294924
TI  - Relevance of endogenous ascorbate and tocopherol for brain cell vitality
      indicated by photon emission.
AB  - In vitro lipid peroxidation of brain cell membranes was recorded directly by
      monitoring the concomitant photon emission. Chemiluminescence appeared
      spontaneously after disintegration of vital brain cells (pig brain cell
      homogenate, isolated oligodendrocytes), decreasing the high intracellular
      ascorbate concentration in the vital glial cell (1 mmol/L) to a lower overall
      concentration (< 100 mumol/L). This had a prooxidant effect in the homogenate.
      Intracellular high antioxidant ascorbate concentrations were also efficient at
      protecting membrane lipids of vital oligodendrocytes against extracellular low
      prooxidant ascorbate concentrations (50 mumol/L). The intramembranous alpha
      tocopherol content limited the antioxidant efficiency of ascorbate. With
      physiological concentrations (0.4 nmol of iron to 0.1 nmol of tocopherol per
      milliter of membrane suspension), a 50% inhibition of lipid peroxidation was
      obtained with 410 nmol/ml ascorbate; this was reduced to 90 nmol/ml in the case
      of fivefold increased tocopherol content. So in vivo ascorbate concentrations
      were sufficient to protect against lipid peroxidation. Only when endogenous
      tocopherol was decreased to 20% was the in vivo intracellular ascorbate
      concentration too small for antioxidative protection of lipids. The product of
      tocopherol concentration and ascorbate concentration, effective for 50%
      inhibition of lipid peroxidation, remained constant. When iron concentrations
      were increased 10(4)-fold, maximal chemiluminescence and malondialdehyde
      formation were increased twofold and less than 50%, respectively. This
      quantitative description of the interactions between vitamin E, vitamin C, and
      iron are relevant to the modification of interpretations of pathological
      conditions in parkinsonian brains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294925
TI  - Region-selective decreases in densities of [3H]tryptamine binding sites in
      autopsied brain tissue from cirrhotic patients with hepatic encephalopathy.
AB  - The distribution of [3H]tryptamine binding sites, in autopsied brain tissue from
      cirrhotic patients with hepatic encephalopathy (HE) and an equal number of age
      matched control subjects free from hepatic, neurological, or psychiatric
      disorder, was investigated. Scatchard analysis demonstrated a heterogeneous
      distribution for this binding site, with the highest density being observed in
      hippocampus >> frontal cortex = caudate nucleus > temporal cortex = cerebellum.
      When comparing [3H]tryptamine binding site densities in control brain tissue with
      that in brain tissue from patients with HE, significant decreases in densities
      were observed in the frontal cortex (by 56%, p < 0.001), hippocampus (by 43%, p <
      0.001), and caudate nucleus (by 41%, p < 0.01) of the HE group. Binding site
      affinities were within normal limits. The findings of decreased densities of
      [3H]tryptamine binding sites taken in conjunction with previous reports of
      increased CSF and brain tryptamine concentrations in HE suggest a pathogenic role
      for this neuroactive amine in HE resulting from chronic liver failure.

PMID- 8294926
TI  - Changes in intracellular Ca2+ and energy levels during in vitro ischemia in the
      gerbil hippocampal slice.
AB  - The time course of the decline in energy levels during an in vitro ischemia-like
      condition was compared with changes in intracellular Ca2+ concentration ([Ca2+]i)
      in subregions of the gerbil hippocampal slice [CA1, CA3, and the inner and outer
      portions of the dentate gyrus (DG)]. Hippocampal transverse slices were loaded
      with a fluorescent indicator, rhod-2. During the on-line monitoring of [Ca2+]i,
      the slices were perfused with an in vitro ischemia-like medium (33 degrees C).
      The slices were collected at several experimental time points, frozen, dried, and
      dissected into subregions. The contents of adenine nucleotides (ATP, ADP, and
      AMP) and phosphocreatine (PCr) were measured by HPLC methods. Region-specific and
      acute [Ca2+]i elevations were observed in CA1 approximately 4 min after onset of
      the in vitro ischemia-like condition and also in the inner portion of the DG with
      a delay of 10-40 s. The change in ATP levels was related to the increase in
      [Ca2+]i. ATP levels in all subregions gradually decreased before the acute
      [Ca2+]i elevation. Concomitant with the acute [Ca2+]i elevation in CA1 and the
      inner portion of the DG, ATP levels in the subregions rapidly decreased, whereas
      declines in levels of high-energy-charge phosphates were gradual in CA3 and the
      outer portion of the DG, in which the remarkable [Ca2+]i elevation was not
      observed. These results suggest that ATP depletion observed in CA1 and the inner
      portion of the DG is due to the region-specific increase in [Ca2+]i, which
      activates a Ca(2+)-ATP-driven pump and produces a subsequent fall in neuronal ATP
      content.

PMID- 8294927
TI  - The effects of Alzheimer's disease, other dementias, and premortem course on beta
      amyloid precursor protein messenger RNA in frontal cortex.
AB  - There are conflicting data regarding alterations in beta-amyloid precursor
      protein (APP) mRNAs in Alzheimer's disease (AD). This may be due partly to
      variables such as agonal state and choice of control group. We have used in situ
      hybridization histochemistry to study expression of APP mRNAs, with and without
      the domain encoding the Kunitz protease inhibitor, in a way that overcomes some
      of the limitations of the current data. Tissue from frontal cortex was collected
      at rapid autopsy from patients with AD or other cognitive impairments whose
      terminal phase was prospectively assessed. There were three main findings.
      Firstly, the amount of APP mRNAs correlated strongly with glutamate decarboxylase
      activity and was reduced in association with terminal pyrexia. These correlations
      suggest that agonal state affects APP mRNA and, therefore, that differences in
      premortem course may contribute to the varying changes in APP transcript
      abundance reported in AD. Secondly, a reduction of both forms of APP mRNA,
      normalized to polyadenylated mRNA, was found in AD compared with normal controls
      and with non-AD dementias. This supports findings that the APP-related pathology
      of AD is not due to overexpression of APP mRNA or an altered proportion of Kunitz
      protease inhibitor-containing isoforms. Thirdly, the amount of APP mRNA
      correlated inversely with that of heat-shock protein (hsx70) mRNA. This
      relationship was unexpected given current theories that APP expression occurs as
      part of a stress response, and suggests that other factors predominate in
      determining neocortical APP mRNA content in neurodegenerative disorders.

PMID- 8294928
TI  - Regulation of intracellular pH in guinea pig cerebral cortex ex vivo studied by
      31P and 1H nuclear magnetic resonance spectroscopy: role of extracellular
      bicarbonate and chloride.
AB  - The role of transmembrane processes that are dependent on external anions in the
      regulation of cerebral intracellular pH (pHi), high-energy metabolites, and
      lactate was investigated using 31P and 1H NMR spectroscopy in an ex vivo brain
      slice preparation. During oxygenated superfusion, removal of external HCO3-/CO2
      in the presence of Na+ led to a sustained split of the inorganic phosphate (Pi)
      peak so that the pHi indicated by one part of the peak was 0.38 pH units more
      alkaline and by the other part 0.10 pH units more acidic at 5 min than in the
      presence of HCO3-. The pH in the compartment with a higher pHi value returned to
      7.29 +/- 0.04 by 10.5 min of superfusion in a HCO3(-)-free medium, whereas the
      pHi in an acidic compartment was reduced to 7.02. In the presence of 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid or the absence of external Cl-,
      removal of HCO3- caused alkalinization without split of the Pi peak. Both
      treatments reduced the rate of pHi normalization following alkalinization.
      Simultaneous omission of external HCO3- and Na+ did not inhibit alkalinization of
      the pHi following CO2 exit. All these data show that the acid loading mechanism
      at neutral pHi is mediated by an Na(+)-independent anion transport. During severe
      hypoxia, pHi dropped from 7.29 +/- 0.05 to 6.13 +/- 0.16 and from 7.33 +/- 0.03
      to 6.67 +/- 0.05 in the absence and presence of HCO3-, respectively, in Na(+)
      containing medium. Lactate accumulated to 18.7 +/- 2.8 and 19.6 +/- 1.5 mmol/kg
      under the respective conditions. In the HCO3(-)-free medium supplemented with 1
      mM amiloride, the pHi fell only to 6.94 +/- 0.08 despite the lactate
      concentration of 18.9 +/- 2.4 mmol/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294929
TI  - Transport of zinc-65 at the blood-brain barrier during short cerebrovascular
      perfusion in the rat: its enhancement by histidine.
AB  - Zinc-65 transport into different regions of rat brain has been measured during
      short vascular perfusion of one cerebral hemisphere with an oxygenated HEPES
      containing physiological saline at pH 7.40. The [Zn2+] was buffered with either
      bovine serum albumin or histidine. In each case uptake was linear with time up to
      90 s. 65Zn flux into brain in the presence of albumin followed Michaelis-Menten
      kinetics and for parietal cortex had a Km of 16 nM and a Vmax of 44 nmol/kg/min.
      Increasing concentrations of L-histidine enhanced 65Zn flux into brain at [Zn2+]
      values between 1 and 1,000 nM. The combined effect of [histidine] and [Zn2+] was
      best accounted for by a function of [ZnHis+], i.e., flux = 64.4.[ZnHis+]/(390 +
      [ZnHis+]) + 0.00378.[ZnHis+], with concentrations being nanomolar. D-Histidine
      had an influence similar to that of L-histidine. 65Zn flux in the presence of 100
      microM L-histidine was not affected by either 500 microM L-arginine or 500 microM
      L-phenylanine. The results indicate specific transport of Zn2+ across the plasma
      membranes of brain endothelium. The enhancement due to histidine has been
      attributed to diffusion of ZnHis+ across unstirred layers "ferrying" zinc to and
      from transport sites.

PMID- 8294930
TI  - The peripheral-type benzodiazepine receptor is present in astrocytes but is not a
      primary site of action for convulsants/anticonvulsants.
AB  - High-affinity binding sites for [3H]PK 11195 and [3H]Ro 5-4864 with the
      properties of the peripheral-type benzodiazepine receptor were detected in
      primary cultures of both mouse neocortical and cerebellar astrocytes. The binding
      sites were enriched in mitochondrial fractions on differential centrifugation. An
      18-kDa polypeptide was specifically photolabelled in cerebellar astrocytes by
      [3H]PK 14105, a photolabel for the peripheral-type benzodiazepine receptor.
      However, this polypeptide did not show any reactivity with an antiserum
      previously raised against the corresponding polypeptide from rat adrenal gland.
      Various anticonvulsant and convulsant agents were tested for their ability and
      potency at inhibiting [3H]Ro 5-4864 binding to neocortical astrocytes. Many of
      these compounds previously reported to be inhibitors of diazepam binding to
      neocortical astrocytes, proved ineffective in this study. No correlation was
      observed between convulsant/anticonvulsant potency and ability to inhibit [3H]Ro
      5-4864 binding to the peripheral-type benzodiazepine receptor in these cells.
      Thus, whereas some convulsants and anticonvulsants might interact with this
      astrocytic receptor, such a system has no validity as a general screening method
      for these agents.

PMID- 8294931
TI  - Alpha, beta I, beta II, delta, and epsilon protein kinase C isoforms and compound
      activity in the sciatic nerve of normal and diabetic rats.
AB  - Defective protein kinase C (PKC) has been implicated in impaired Na+,K(+)-ATPase
      activity in the sciatic nerve of streptozotocin-induced diabetic rats. In the
      present study, alpha, beta I, beta II, gamma, delta, and epsilon isoform-specific
      antibodies were used in parallel to the measurement of compound PKC activity for
      the characterization of PKC distribution and isoform expression in sciatic nerves
      of normal and diabetic rats. To distinguish isoform expression between the axonal
      and glial compartments, PKC isoforms were evaluated in nerves subjected to
      Wallerian degeneration and in a pure primary Schwann cell culture. alpha, beta I,
      beta II, delta, and epsilon but no gamma isoforms were detected in sciatic nerve.
      Similar immunoreactivity was observed in degenerated nerves 3-4 days after
      transection except for diminished beta I and epsilon species; in Schwann cell
      cultures, only alpha, beta II, delta, and epsilon were detected. In normal
      nerves, two-thirds of PKC compound activity was found in the cytosol and 50% of
      total enzyme activity translocated to the Na+,K(+)-ATPase-enriched membrane
      fraction with phorbol myristate acetate. Similar redistribution patterns were
      observed for the immunoreactivity of all isoforms with the exception of delta,
      which did not translocate to the membrane with phorbol myristate acetate. No
      abnormality in compound PKC activity, in the immunoreactive intensity, or in the
      distribution of PKC isoforms could be detected in rat sciatic nerve after 6-12
      weeks of diabetes. Thus, defective activation rather than decreased intrinsic PKC
      activity may occur in diabetic neuropathy.

PMID- 8294932
TI  - Neurochemical and neuroprotective effects of some aliphatic propargylamines: new
      selective nonamphetamine-like monoamine oxidase B inhibitors.
AB  - Aliphatic N-propargylamines have recently been discovered to be highly potent,
      selective, and irreversible monoamine oxidase B (MAO-B) inhibitors. N-Methyl-N-(2
      pentyl)propargylamine (M-2-PP) and N-methyl-N-(2-hexyl) propargylamine (2-HxMP),
      for example, are approximately fivefold more potent that l-deprenyl at inhibiting
      mouse brain MAO-B activity following oral administration. These inhibitors are
      nonaromatic compounds and are chemically quite different from other known MAO-B
      inhibitors. Some of their neurochemical and neuroprotective properties have been
      evaluated and compared with those of l-deprenyl. We have confirmed that these new
      inhibitors selectively inhibit MAO-B activity both in vitro and in vivo. 2
      Phenylethylamine levels were substantially increased following administration of
      M-2-PP, but the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic
      acid, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid were not affected
      except at high, nonselective doses. Chronic oral administration of l-deprenyl and
      M-2-PP causes selective inhibition of MAO-B activity and increases dopamine
      levels in mouse caudate. M-2-PP, like l-deprenyl, has been shown to be potent in
      protecting against MPTP-induced damage in the mouse. N-(2-Chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP-4), a noradrenaline neurotoxin, is not an MAO substrate.
      Its noradrenaline-depleting effects were substantially mitigated by l-deprenyl as
      well as by M-2-PP and 2-HxMP in the mouse hippocampus. Administration of 2
      phenylethylamine, however, failed to reverse the effect of DSP-4. The
      neuroprotective effect of M-2-PP and 2-HxMP is apparently unrelated to the uptake
      of DSP-4.

PMID- 8294933
TI  - Phospholipase A2 stimulation by methyl mercury in neuron culture.
AB  - In primary prelabeled cultures of cerebellar granule cells, methyl mercury (MeHg)
      induced a concentration- and time-dependent release of [3H]arachidonic acid. MeHg
      induced [3H]arachidonate release was partially dependent on the extracellular
      Ca2+ concentration. MeHg at 10-20 microM also stimulated basal 45Ca2+ uptake
      after 20 min of incubation at 37 degrees C, and at 10 microM inhibited K+
      depolarization-stimulated uptake. MeHg stimulated [3H]arachidonate uptake, but
      had no effect on the rate of phospholipid reacylation. Phospholipase A2 (PLA2)
      activation preceded cytotoxicity, but at higher concentrations of MeHg such
      dissociation was not evident. Inhibition of MeHg-induced PLA2 activation by 100
      microM mepacrine failed to modify cytotoxicity. MeHg-induced lipoperoxidation,
      measured as the production of thiobarbituric acid-reacting products, was
      inhibited by alpha-tocopherol without inhibition of [3H]arachidonate release. The
      absence of alpha-tocopherol inhibition of MeHg-induced arachidonate release
      precludes a causal role for lipoperoxide-induced PLA2 activation in this system.
      Moreover, MeHg induced an increased susceptibility of unilamellar vesicles to
      exogenous PLA2 in the presence of low Ca2+ concentrations without evidence of
      lipid peroxidation. [3H]Arachidonate incorporation into granule neuron
      phospholipids was analyzed by isocratic HPLC analysis. Relatively high
      proportional incorporation was found in the combined phosphatidylcholine
      fractions and phosphatidylinositol. With MeHg, an increase in the relative
      specific activity of incorporation was found in the phosphatidylinositol
      fraction, indicating a preferential turnover in this phospholipid species in the
      presence of MeHg.

PMID- 8294934
TI  - Increase in the extracellular histamine concentration in the rat striatum by mu
      opioid receptor activation.
AB  - The effects of morphine and selective ligands for mu-, kappa-, and delta-opioid
      receptors on the extracellular histamine (HA) concentration in the striatum of
      freely moving rats were examined by in vivo microdialysis. On the day after
      implantation of the dialysis probe, the HA output per 30-min period was measured
      using HPLC-fluorometry. Morphine (3.8 mg/kg, s.c.) significantly increased the HA
      output by approximately 200% 1-3 h after treatment. This effect was completely
      antagonized by naltrexone (1.6 mg/kg, s.c.). The HA output decreased to a level
      below 10% of the basal value by 4 h after treatment with (S)-alpha-fluoromethyl
      histidine (77 mg/kg, s.c.). In such animals, morphine (3.8 mg/kg, s.c.) had no
      influence on the HA output. [D-Ala2,MePhe4,Gly(ol)5]Enkephalin (DAGO; 0.2
      microgram, i.c.v.), a selective mu-agonist, significantly increased the HA output
      by approximately 150% 0.5-1.5 h after treatment, and this effect was also
      completely blocked by naltrexone. A selective kappa-agonist, U-50,488 (3.8 and
      7.6 mg/kg, s.c.), and a selective delta-agonist, [D-Pen2,D-Pen5]enkephalin (0.5
      and 2 micrograms, i.c.v.), had no effect on the HA output. These findings suggest
      that the stimulation of mu-opioid receptors by morphine and DAGO increases the
      extracellular HA concentration by accelerating HA release from nerve endings.

PMID- 8294935
TI  - Purification and characterization of kynurenine aminotransferase I from human
      brain.
AB  - Two kynurenine aminotransferases (KATs), arbitrarily termed KAT I and KAT II, are
      capable of producing the neuroinhibitory brain metabolite kynurenic acid from L
      kynurenine in human brain tissue. Here we describe the purification of KAT I to
      homogeneity and the subsequent characterization of the enzyme using
      physicochemical, biochemical, and immunological methods. KAT I was purified from
      human brain approximately 2,000-fold with a yield of 2%. Assessed by
      polyacrylamide gel electrophoresis, KAT I migrated toward the anode as a single
      protein with a mobility of 0.5. The pure enzyme was found to be a dimer
      consisting of two identical subunits of approximately 60 kDa. Among several oxo
      acids tested, KAT I showed highest activity with 2-oxoisocaproate. Kinetic
      analyses of the pure enzyme revealed an absolute Km of 2.0 mM and 10.0 mM for L
      kynurenine and pyruvate, respectively. KAT I activity was substantially inhibited
      by L-glutamine, L-phenylalanine, and L-tryptophan, using either pyruvate (1 mM)
      or 2-oxoisocaproate (1 mM) as a cosubstrate. L-Tryptophan inhibited enzyme
      activity noncompetitively with regard to pyruvate (Ki = 480 microM) and
      competitively with regard to L-kynurenine (Ki = 200 microM). Anti-KAT I
      antibodies were produced against pure KAT I and were partially purified by
      conventional techniques. Immunotitration and immunoblotting analyses confirmed
      that KAT I is clearly distinct from both human KAT II and rat kynurenine-pyruvate
      aminotransferase. Pure human KAT I and its antibody will serve as valuable tools
      in future studies of kynurenic acid production in the human brain under
      physiological and pathological conditions.

PMID- 8294936
TI  - Changes in neurofilament protein NF-L and NF-H immunoreactivity following kainic
      acid-induced seizures.
AB  - Postlesion plasticity of neuronal processes might contribute to secondary
      spontaneous seizures after kainic acid administration. In this study,
      neurofilament (NF) proteins were examined following intraperitoneal injection of
      kainic acid, and special reference was given to temporal changes in quantity and
      quality of the NF light (NF-L) and heavy (NF-H) subunits. A pronounced decrease
      in phosphorylation-related immunoreactivity of NF-H occurred as early as 1 day
      after the injection in the amygdala/pyriform cortex, hippocampus, striatum, and
      dorsal cerebral cortex. A shift of NF-H from the phosphorylated to
      nonphosphorylated form was evident in immunoblots, suggesting dephosphorylation
      contributed to the decrease. Decreases in NF-L and phosphorylated NF-H contents
      in the limbic structure at 3 days were correlated with the increasing kainic acid
      doses from 2.5 to 10 mg/kg. The degradation pattern in immunoblots with
      antibodies against NF-L indicated that the decrease in NF-L was probably due to
      calcium-activated proteolysis. NF-L and phosphorylated NF-H contents secondarily
      increased from 9 days onward, with approximately 20% above the control level of
      phosphorylated NF-H immunoreactivity at 27 days in the amygdala/pyriform cortex
      and ventral hippocampus. Immunohistochemical examination of the hippocampus
      revealed that an increase of NF staining in the mossy fiber system may contribute
      to the NF recovery in this region. Furthermore, the temporal changes of NF-L and
      phosphorylated NF-H contents were positively correlated with those of the
      neuronal cell adhesion molecule, a neuritic growth cone marker, substantiating
      postlesion regenerative reactions of NF proteins. Functional consequences of the
      NF plasticity remain to be identified.

PMID- 8294937
TI  - Site-directed mutagenesis of active site residues reveals plasticity of human
      butyrylcholinesterase in substrate and inhibitor interactions.
AB  - In search of the molecular mechanisms underlying the broad substrate and
      inhibitor specificities of butyrylcholinesterase (BuChE), we employed site
      directed mutagenesis to modify the catalytic triad residue Ser198, the acyl
      pocket Leu286 and adjacent Phe329 residues, and Met437 and Tyr440 located near
      the choline binding site. Mutant proteins were produced in microinjected Xenopus
      oocytes, and Km values towards butyrylthiocholine and IC50 values for the
      organophosphates diisopropylfluorophosphonate (DFP),
      diethoxyphosphinylthiocholine iodide (echothiophate), and
      tetraisopropylpyrophosphoramide (iso-OMPA) were determined. Substitution of
      Ser198 by cysteine and Met437 by aspartate nearly abolished activity, and other
      mutations of Ser198 completely abolished it. Tyr440 and Leu286 mutants remained
      active, but with higher Km and IC50 values. Rates of inhibition by DFP were
      roughly parallel to IC50 values for several Leu286 mutants. Both Km and IC50
      values increased for Leu286 mutants in the order Asp < Gln < Lys. In contrast,
      cysteine, leucine, and glutamine mutants of Phe329 displayed unmodified Km values
      toward butyrylthiocholine, but up to 10-fold decreased IC50 values for DFP, iso
      OMPA, and echothiophate. These findings add Tyr440 and Phe329 to the list of
      residues interacting with substrate and ligands, demonstrate plasticity in the
      active site region of BuChE, and foreshadow the design of recombinant BuChEs with
      tailored scavenging properties.

PMID- 8294938
TI  - Cholinesterases display genuine arylacylamidase activity but are totally devoid
      of intrinsic peptidase activities.
AB  - The purpose of this article was to evaluate the intrinsic character of
      arylacylamidase and peptidase activities that are often detected along with
      cholinesterase activities. Various pools of commercial or affinity-purified
      acetylcholinesterases (AChEs) were examined. Affinity-purified AChE displays
      esterase- and amidase-specific activities that are similarly enriched when
      compared with commercial AChE. By contrast, commercial AChE exhibits much higher
      tryptic-like and carboxypeptidase-specific activities than the affinity-purified
      enzyme. The parallel enrichment in esterase and arylacylamidase suggests that
      these two activities are copurified, whereas peptidases do not seem to behave
      similarly. We show that trypsinolysis or spontaneous degradation of affinity
      purified AChE leads to the conversion of the 75-kDa monomer protein into two
      fragments of 50 and 25 kDa after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis. However, these modifications are without effect on the
      esterase, arylacylamidase, and peptidase activities. This clearly shows that AChE
      does not behave as a zymogen of peptidases that would have been activated on
      autolysis of AChE. Immunoprecipitation of AChEs with a purified monoclonal
      antibody directed toward electric eel AChE totally separated the esterase and
      arylacylamidase activities (pellet) from peptidase activities (supernatant). The
      immunoprecipitated AChEs could be dissociated from the interaction with IgGs.
      These resolubilized AChE preparations have kept the same percentage of initial
      esterase and arylacylamidase activities but were totally devoid of peptidase
      activities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294939
TI  - Distinctly phosphorylated neurofilaments in different classes of neurons.
AB  - Recent immunohistochemical experiments revealed that specific anti-neurofilament
      monoclonal antibodies yield distinct patterns in different types of neurons. This
      led to the suggestion that neurofilaments are a family of heterogeneous molecules
      whose occurrence and distribution are a function of cell type. In the present
      study we examined the hypothesis that this heterogeneity is due to differences in
      the extent of phosphorylation of neurofilament proteins in distinct types of
      neurons. In view of the large number of potential phosphorylation sites on the
      heavy neurofilament protein (NF-H), we focused on this protein and examined its
      extent of phosphorylation in different types of neurons. This was performed using
      neurofilaments isolated from axons of the cholinergic bovine ventral root motor
      neurons and of the chemically heterogeneous bovine dorsal root neurons. Two
      dimensional gel electrophoresis revealed that the isoelectric point of ventral
      root NF-H (pl 5.10) was approximately 0.2 pl units more acidic than that of
      dorsal root NH-F. This difference was abolished by treating the neurofilaments
      with alkaline phosphatase, suggesting that the excess negative charge of ventral
      root NF-H is due to increased levels of phosphorylation. Amino acid analysis
      confirmed that the phosphoserine content of ventral root NF-H (27.2 +/- 2.5% of
      the serines) is markedly higher than that of dorsal root NF-H (15.5 +/- 6.2% of
      the serines). These findings provide a novel system for studying the biochemistry
      and function of distinctly phosphorylated neurofilaments in different types of
      neurones.

PMID- 8294940
TI  - Expression of apolipoprotein A-I in porcine brain endothelium in vitro.
AB  - Apolipoprotein (apo) A-I is the major protein component of high-density
      lipoproteins (HDLs), which are responsible for reverse cholesterol transport from
      peripheral tissues to the liver. A low level of plasma HDL is correlated with
      susceptibility to atherosclerosis and coronary heart disease. Mammalian apo A-I
      synthesis has been attributed mainly to liver and intestine. Recently, apo A-I
      expression has been shown in porcine brain capillaries, suggesting an independent
      lipid metabolism within the brain. In this study, protein synthesis and secretion
      were investigated in primary cultures of porcine brain microvascular endothelial
      cells and compared with those in large vessel endothelium. Active protein
      synthesis in vitro was demonstrated by metabolic labeling. Cerebral endothelial
      cells were shown to secrete apo A-I into the culture supernatant, whereas aortic
      endothelial cells were negative for apo A-I expression. Further studies of
      transcriptional regulation showed that cerebral endothelium was responsive to apo
      A-I-inducing agents, such as cholesterol, insulin, and retinoic acid, as
      previously shown in human hepatoma HepG2 cells. Thus, cultures of porcine
      cerebral endothelial cells may represent a suitable model for physiological
      studies of apo A-I-regulation with regard to brain lipid metabolism and blood
      brain barrier function. To investigate the interspecies conservation of
      regulatory elements, 178 bp of the 5' flanking region of the porcine apo A-I gene
      was cloned using PCR techniques. Alignments of the cDNA, of the deduced apo A-I
      protein sequence, and of the 5' promoter region with the corresponding genomic
      sequences of different species show a high degree of similarity between the
      porcine and the primate apo A-I genes, thus indicating a similar function and
      possibly common regulatory mechanisms in those species. In contrast, the rodent
      and avian apolipoprotein A-I promoter sequences differed significantly.

PMID- 8294941
TI  - Splicing of the muscle-specific plasma membrane Ca(2+)-ATPase isoforms PMCA1c is
      associated with cell fusion in C2 myocytes.
AB  - The regulation of intracellular calcium is essential for proper muscle function.
      Muscle cells have several mechanisms for dealing with the rapid and large changes
      in cytosolic calcium level that occur during contraction. Among these is the
      plasma membrane Ca(2+)-ATPase (PMCA), which pumps calcium from the cytosol to the
      extracellular space. We have previously shown that in human fetal muscle the
      PMCA1 isoforms present are PMCA1a-d, with PMCA1b and c predominating. Alternative
      splicing of mRNAs encoding proteins involved in muscle contraction is common in
      developing muscle. Therefore, we examined the expression of muscle-specific PMCA
      mRNAs in pre- and postfusion mouse C2 myoblasts. The housekeeping form of the
      CA(2+)-ATPase, PMCA1b, was found at all times and under all conditions. However,
      the other predominating isoform found in muscle, PMCA1c, was expressed on myotube
      formation. Simple cell-cell contact was not sufficient to induce PMCA1c
      expression, as cells plated at confluence but harvested before myotubule
      formation did not express PMCA1c. The induction of this muscle-specific Ca(2+)
      ATPase at myotube formation suggests that it may play an important role in muscle
      function.

PMID- 8294942
TI  - Alzheimer's disease abnormally phosphorylated tau is dephosphorylated by protein
      phosphatase-2B (calcineurin).
AB  - Abnormally hyperphosphorylated tau is the major protein subunit of paired helical
      filaments in Alzheimer brains. We have examined its site-specific
      dephosphorylation by different protein phosphatases. Dephosphorylation of tau was
      monitored by its interaction with several phosphorylation-dependent antibodies.
      Alzheimer tau was dephosphorylated by brain protein phosphatase-2B at the
      abnormally phosphorylated sites Ser46, Ser199, Ser202, Ser235, Ser396, and
      Ser404, and its relative mobility on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis shifted to that of normal tau. Protein phosphatases-1 and -2A
      could dephosphorylate only some of the above six phosphorylation sites. These
      results indicate that protein phosphatase-2B might be involved in
      hyperphosphorylation of tau in Alzheimer's disease.

PMID- 8294943
TI  - A new approach to analysis and display of local lipophilicity/hydrophilicity
      mapped on molecular surfaces.
AB  - A new method for display and analysis of lipophilic/hydrophilic properties on
      molecular surfaces is presented. The present approach is based on the concept of
      Crippen and coworkers that the overall hydrophobicity of a molecule (measured as
      the logarithm of the partition coefficient in an octanol/water system) can be
      obtained as a superposition of single atom contributions. It is also based on the
      concept of molecular lipophilicity potentials (MLP) first introduced by Audry and
      coworkers in order to establish a 3D lipophilicity potential profile in the
      molecular environment. Instead of using a l/r- or an exponential distance law
      between the atomic coordinates and a point on the molecular surface, a new
      distance dependency is introduced for the calculation of an MLP-value on the
      solvent-accessible surface of the molecule. In the present formalism the Crippen
      values (introduced for atoms in their characteristic structural environment) are
      'projected' onto the van der Waals surface of the molecule by a special weighting
      procedure. This guarantees that only those atomic fragments contribute
      significantly to the surface values that are in the close neighbourhood of the
      surface point. This procedure not only works for small molecules but also allows
      the characterization of the surfaces of biological macromolecules by means of
      local lipophilicity. Lipophilic and hydrophilic domains can be recognized by
      visual inspection of computer-generated images or by computational procedures
      using fuzzy logic strategies. Local hydrophobicities on different molecular
      surfaces can be quantitatively compared on the basis of the present approach.

PMID- 8294944
TI  - A Monte Carlo pharmacophore generation procedure: application to the human PAF
      receptor.
AB  - A novel pharmacophore definition procedure is described, which uses a Monte Carlo
      method to superimpose molecules. Pharmacophore space is searched by a technique
      similar to high temperature annealing. Subsequent refinement of candidate
      pharmacophores by energy minimization produces low-energy conformations that may
      be involved in receptor binding. The method has been applied to compounds that
      bind to the human platelet-activating factor (PAF) receptor. Alternative binding
      site models for the PAF receptor are presented and discussed.

PMID- 8294945
TI  - Computer-aided drug design: a free energy perturbation study on the binding of
      methyl-substituted pterins and N5-deazapterins to dihydrofolate reductase.
AB  - Molecular dynamics simulation and free energy perturbation techniques have been
      used to study the relative binding free energies of 8-methylpterins and 8-methyl
      N5-deazapterins to dihydrofolate reductase (DHFR). Methyl-substitution at the 5,
      6 and 7 positions in the N-heterocyclic ring gives rise to a variety of ring
      substituent patterns and biological activity: several of these methyl derivatives
      of the 8-methyl parent compounds (8-methylpterin and 8-methyl-N5-deazapterin)
      have been identified as substrates or inhibitors of vertebrate DHFR in previous
      work. The calculated free energy differences reveal that the methyl-substituted
      compounds are thermodynamically more stable than the primary compounds (8
      methylpterin and 8-methyl-N5-deazapterin) when bound to the enzyme, due largely
      to hydrophobic hydration phenomena. Methyl substitution at the 5 and/or 7
      positions in the 6-methyl-substituted compounds has only a small effect on the
      stability of ligand binding. Furthermore, repulsive interactions between the 6
      methyl substituent and DHFR are minimal, suggesting that the 6-methyl position is
      optimal for binding. The results also show that similarly substituted 8
      methylpterins and 8-methyl-N5-deazapterins have very similar affinities for
      binding to DHFR. The computer simulation predictions are in broad agreement with
      experimental data obtained from kinetic studies, i.e. 6,8-dimethylpterin is a
      more efficient substrate than 8-methylpterin and 6,8-dimethyl-N5-deazapterin is a
      better inhibitor than 8-methyl-N5-deazapterin.

PMID- 8294946
TI  - Computer-aided structure-affinity relationships in a set of piperazine and 3,8
      diazabicyclo[3.2.1]octane derivatives binding to the mu-opioid receptor.
AB  - Molecular modeling studies were carried out on a set of piperazine and 3,8
      diazabicyclo[3.2.1]octane derivatives with the aim to highlight the main factors
      modulating their affinity for the mu-opioid receptor. Structure-affinity
      relationships were developed with the aid of molecular mechanics and
      semiempirical quantum-mechanics methods. According to our proposed
      pharmacodynamic model, the binding to the mu-receptor is promoted by the
      following physico-chemical features: the presence of hydrocarbon fragments on the
      nitrogen ring frame capable of interacting with one of two hypothesized
      hydrophobic receptor pockets; a 'correct' orientation of an N-propionyl side
      chain so as to avoid a sterically hindered region of the receptor; the
      possibility of accepting a hydrogen bond from a receptor site complementary to
      the morphine phenol oxygen.

PMID- 8294947
TI  - Stereochemistry of ulapualides, a new family of tris-oxazole-containing macrolide
      ionophores from marine nudibranchs. A molecular mechanics study.
AB  - A molecular mechanics study of the marine metabolite ulapualide A, which is
      suggested to have ionophoric properties, has been carried out on various metal
      chelated complexes in order to predict the stereochemistry of the natural
      product. The results suggest a stereochemistry for ulapualide A which is closely
      similar to structurally related marine metabolites, whose stereochemistries have
      been established by X-ray crystallography and by partial synthesis.

PMID- 8294948
TI  - Sample-distance partial least squares: PLS optimized for many variables, with
      application to CoMFA.
AB  - Three-dimensional molecular modeling can provide an unlimited number m of
      structural properties. Comparative Molecular Field Analysis (CoMFA), for example,
      may calculate thousands of field values for each model structure. When m is
      large, partial least squares (PLS) is the statistical method of choice for
      fitting and predicting biological responses. Yet PLS is usually implemented in a
      property-based fashion which is optimal only for small m. We describe here a
      sample-based formulation of PLS which can be used to fit any single response
      (bioactivity). SAMPLS reduces all explanatory data to the pairwise 'distances'
      among n samples (molecules), or equivalently to an n-by-n covariance matrix C.
      This matrix, unmodified, can be used to fit all PLS components. Furthermore,
      SAMPLS will validate the model by modern resampling techniques, at a cost
      independent of m. We have implemented SAMPLS as a Fortran program and have
      reproduced conventional and cross-validated PLS analyses of data from two
      published studies. Full (leave-each-out) cross-validation of a typical CoMFA
      takes 0.2 CPU s. SAMPLS is thus ideally suited to structure-activity analysis
      based on CoMFA fields or bonded topology. The sample-distance formulation also
      relates PLS to methods like cluster analysis and nonlinear mapping, and shows how
      drastically PLS simplifies the information in CoMFA fields.

PMID- 8294949
TI  - Role of the caudal fastigial nucleus in saccade generation. I. Neuronal discharge
      pattern.
AB  - 1. The effects of lesions in both human and nonhuman primates have implicated the
      cerebellum in the control of rapid eye movements, i.e., saccades. To examine the
      neural substrate of this control, we recorded the discharge patterns of
      cerebellar output cells in the fastigial nucleus while monkeys tracked a small,
      jumping spot of light. 2. In the caudal fastigial nucleus, neurons discharged for
      saccades in one or several directions. All exhibited a burst. Some also exhibited
      a saccade-related pause in firing either before or after saccades greater than
      approximately 3-5 degrees. Thirty-seven percent discharged only a burst, 44% also
      exhibited a pause before bursts in certain directions, and 19% also paused after
      the saccade-related burst in certain directions. Although many cells discharged
      steadily during intersaccadic intervals, few exhibited a robust relation between
      firing rate and eye position. 3. As a measure of directional selectivity, we
      plotted the burst lead time as a function of saccade direction for saccades of
      similar (10 degrees) radial amplitudes. Of 20 neurons tested, 17 burst earliest
      for contralateral saccades and 1 for upward saccades; 2 others showed little
      dependence on direction. Of 19 additional units tested only in the horizontal
      direction, 18 burst earlier for contralateral saccades. 4. For contralateral
      saccades the burst preceded saccades of all sizes by at least 7.7 ms on average.
      For ipsilateral saccades, the burst preceded small saccades by an average of 10.3
      ms. However, as ipsilateral saccade size increased, the burst began later and
      later relative to saccade onset so that, on average, it always occurred after the
      onset of 20 degrees saccades but well before the saccade ended. 5. Many fastigial
      saccade-related units showed increases in the number of spikes with saccade size
      and in burst duration with saccade duration in one or more directions. For either
      relation the highest average correlation coefficients ranged from 0.6 to 0.65. In
      general, the average correlation coefficients and slopes for either relation were
      slightly larger for contralateral saccades. Pure burst neurons did not display
      better average correlations than neurons that also paused. For neurons that also
      paused either before or after saccades, there was a weak tendency for pause
      duration to increase with the duration of larger saccades. 6. We tested the
      effect of eye position on unit discharge in 13 cells by requiring the monkey to
      make 10 degrees ipsilateral and contralateral saccades from a variety of starting
      positions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294950
TI  - Role of the caudal fastigial nucleus in saccade generation. II. Effects of
      muscimol inactivation.
AB  - 1. We studied the effect of temporarily inhibiting neurons in the caudal
      fastigial nucleus in two rhesus macaques trained to make saccades to jumping
      targets. We placed injections of the gamma-aminobutyric acid (GABA) agonist
      muscimol unilaterally or bilaterally at sites in the caudal fastigial nucleus
      where we had recorded saccade-related neurons a few minutes earlier. 2.
      Unilateral injections (n = 9) made horizontal saccades to the injected side
      hypermetric and those to the other side hypometric (mean gain of 1.37 and 0.61,
      respectively, for 10 degrees target steps, and 1.26 and 0.81 for 20 degrees
      target steps; normal saccade gain was 0.96). Saccades to vertical targets showed
      a small but significant hypermetria and curved strongly toward the side of the
      injection. The trajectories and end points of all targeted saccades were more
      variable than normal. 3. After unilateral injections, centripetal saccades were
      slightly larger than centrifugal saccades (mean gains for ipsilateral saccades
      were 1.42 and 1.31, respectively, for 10 degrees target steps, and 1.37 and 1.15
      for 20 degrees target steps). 4. Unilateral injections increased the average
      acceleration of ipsilateral saccades and decreased the acceleration of
      contralateral saccades. Injections decreased both the acceleration and
      deceleration of vertical saccades. 5. After dysmetric saccades, monkeys acquired
      the target with an abnormally high number of hypometric corrective saccades.
      Injection increased the average number of corrective saccades from 0.6 to 2.1
      after 10 degrees horizontal target steps and from 0.8 to 2.1 after 20 degrees
      steps. The size of each successive corrective saccade in a series decreased, and
      the latency from the previous corrective saccade increased. 6. Bilateral
      injections (n = 2) of muscimol, in which we injected first into the left caudal
      fastigial nucleus and then, within 30 min, into the right, made all saccades
      hypermetric (mean gain for 10 degrees right, left, up, and down saccades was
      1.18, 1.49, 1.43, and 1.10, respectively). Paradoxically, bilateral injection
      decreased both saccade acceleration and deceleration. Saccade trajectories and
      end points were more variable than normal. 7. To account for the effects of our
      injections, we propose that the activity of caudal fastigial neurons on one side
      normally helps to decelerate ipsilateral saccades and helps to accelerate
      contralateral saccades by influencing the feedback loop of the saccade burst
      generator in the brain stem. Without caudal fastigial activity the brain stem
      burst generator produces hypermetric, variable saccades. We therefore also
      propose that the influence of caudal fastigial neurons on the burst generator
      makes saccades more consistent and accurate.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294951
TI  - Identification and characterization of a multifunction neuron contributing to
      defensive arousal in Aplysia.
AB  - 1. The tail withdrawal reflex is mediated by a monosynaptic circuit composed of
      tail sensory and motor neurons, but there appear to be additional neuronal
      elements that also contribute to the reflex. A newly identified interneuron,
      called LP117, was located in the pleural ganglion. This neuron formed a parallel
      excitatory pathway between sensory and motor neurons. The distinguishing feature
      of LP117 was its ability to elicit a long-lasting (5-100 s) excitatory
      postsynaptic potential (EPSP) in the motor neuron. 2. Intracellular labeling of
      LP117 revealed axons projecting to the cerebral and abdominal as well as the
      pedal ganglia. Simultaneous intracellular recordings confirmed the widely
      divergent output of LP117 to tentacle motor neurons in the cerebral ganglion, as
      well as to gill, siphon, and ink motor neurons in the abdominal ganglion. 3. Also
      receiving input were abdominal neurons L29, which excites LFs motor neurons and
      facilitates LE sensory neurons, and L25, which is part of the pattern-generating
      network underlying respiratory pumping. Thus LP117 appears to be a neural element
      important for the conduction of information about tail stimulation to ganglia
      that are not innervated by tail sensory neurons themselves. Moreover, the
      divergent outputs suggest that LP117 is an element of a neural circuit underlying
      defensive arousal. 4. LP117 produced slow EPSPs in several motor neurons. The
      long time course of the EPSP could prolong the burst in the motor neuron produced
      by LP117 itself as well as increase the effectiveness of coincident synaptic
      input. This suggests that an important function of this interneuron is to extend
      the duration of the response to tail stimulation in the motor neuron. This could
      account for the relatively long time course of the motor neuron response to tail
      stimulation compared with that of the sensory neuron. 5. Sensitization is a form
      of nonassociative learning that produces changes in the amplitude and duration of
      reflex responses. It seems unlikely that all of these changes can be attributed
      to enhanced amplitude of the sensory-motor synapse, however. Therefore LP117 may
      itself be a site of plasticity for reflexes elicited by tail stimulation.

PMID- 8294952
TI  - The role of interneurons in controlling the tail-withdrawal reflex in Aplysia: a
      network model.
AB  - 1. The contributions of monosynaptic and polysynaptic circuitry to the tail
      withdrawal reflex in the marine mollusk Aplysia californica were assessed by the
      use of physiologically based neural network models. Effects of monosynaptic
      circuitry were examined by the use of a two-layer network model with four sensory
      neurons in the input layer and one motor neuron in the output layer. Results of
      these simulations indicated that the monosynaptic circuit could not account fully
      for long-duration responses of tail motor neurons elicited by tail stimulation.
      2. A three-layer network model was constructed by interposing a layer of two
      excitatory interneurons between the input and output layers of the two-layer
      network model. These interneurons had properties mimicking those of the recently
      described interneuron LP117, receiving excitatory input from pleural sensory
      neurons and evoking a biphasic excitatory postsynaptic potential (EPSP) in pedal
      motor neurons (Cleary and Byrne 1993). The three-layer model could account for
      long-duration responses in motor neurons. 3. Sensory neurons are a known site of
      plasticity in Aplysia. Synaptic plasticity was incorporated into the three-layer
      model by altering the magnitudes of conductance changes evoked in motor neurons
      and interneurons by presynaptic sensory neurons. In these simulations the
      excitatory interneurons converted an amplitude-coded input into an amplitude- and
      duration-coded output, allowing the three-layer network to support a large range
      of output amplitudes and durations. 4. Synaptic plasticity at more than one locus
      modified dramatically the input-output relationship of the three-layer network
      model. This feature gave the model redundancy in its plastic properties and
      points to the possibility of distributed memory in the circuitry mediating
      withdrawal reflexes in Aplysia. Multiple sites of control over the response of
      the network would likely allow a more diverse repertoire of responses.

PMID- 8294953
TI  - Motor-unit recruitment in self-reinnervated muscle.
AB  - 1. Recruitment order of motor units in self-reinnervated medial gastrocnemius
      (MG) muscles was studied in decerebrate cats 16 mo after surgical reunion of the
      cut MG nerve. Pairs of MG motor units were isolated by dual microelectrode
      penetration of ventral roots to measure their recruitment sequence during
      cutaneous reflexes in relation to their physiological properties. 2.
      Physiological properties of reconstituted motor units appeared normal, as
      expected. Also normal were the relationships among these properties: twitch and
      tetanic tension tended to increase with axonal conduction velocity and decrease
      with twitch contraction time. A small fraction of motor units (10/116) in
      reinnervated muscles produced either no measurable tension or unusually large
      amounts of tension compared with controls. This was the only distinct feature of
      the sample of reconstituted units. 3. In muscles reinnervated after nerve
      section, stretch was notably ineffective in eliciting reflex contraction of MG
      muscles or their constituent motor units (only 5/116 units). Incomplete recovery
      from nerve section was probably the cause of this impairment, because stretch
      reflexes were readily evoked in adjacent untreated muscles and in one
      reinnervated MG muscle that was studied 16 mo after nerve crush. In contrast with
      the ineffectiveness of muscle stretch, sural nerve stimulation succeeded in
      recruiting 49/116 units, a proportion fairly typical of normal MG muscles. 4. The
      contractions of the first unit recruited in cutaneous reflexes tended to be
      slower and less forceful than those of the other unit in a pair. By these
      measures, recruitment obeyed the size principle. This recruitment order with
      respect to unit contractile properties was not significantly different (P > 0.05)
      between untreated and reinnervated muscles but was significantly (P < 0.005)
      different from random order in both groups. The same recruitment pattern was
      observed for pairs of motor units sampled from the muscle reinnervated after
      nerve crush, whether units were recruited by muscle stretch or sural nerve
      stimulation. 5. The usual tendency for motor units with slower conduction
      velocity (CV) to be recruited in sural nerve reflexes before those with faster CV
      was not strong in reinnervated muscles. After nerve section the proportion of
      units exhibiting the usual recruitment pattern was not significantly different (P
      > 0.05) from a random pattern for CV. 6. The central finding is that the normal
      recruitment patterns recover from nerve injury in a muscle that is reinnervated
      by its original nerve. By contrast, stretch reflexes do not recover well from
      nerve section, and this deficiency may contribute to motor disability.

PMID- 8294954
TI  - Declining inhibition in ipsi- and contralateral lumbar motoneurons during
      contractions of an ankle extensor muscle in the cat.
AB  - 1. Motoneurons of pretibial ankle flexor and knee flexor and extensor muscles
      were recorded intracellularly in chloralose- or pentobarbitone-anesthetized cats
      during sustained submaximal contractions of either ipsi- or contralateral
      gastrocnemius medialis muscle (GM). 2. In a majority of ipsilateral motoneurons,
      a sustained GM contraction elicited inhibitory potentials that quickly subsided
      before the end of the contraction. An abrupt increase in contractile force could
      elicit a new series of inhibitory potentials, which declined again in spite of a
      maintained force level. 3. Contraction-induced effects were only exceptionally
      detected in contralateral triceps surae and plantaris motoneurons. In a small
      number of pretibial flexor and knee flexor and extensor motoneurons, declining
      inhibitions were observed during sustained contractions of the contralateral GM
      muscle. 4. At the onset of GM contractions, a variety of motoneurons uniformly
      receive inhibitory inputs that are quickly filtered out. Although the functional
      significance of this widespread initial inhibition remains to be elucidated, its
      rapid decline seems useful to allow subsequent recruitment of motor units as may
      be required for coordination of posture and movement. 5. Tendon organs are
      activated during muscle contraction, but it is not certain whether Ib inputs from
      GM can account for all the effects observed. Contribution of other afferents was
      considered and tested using a different experimental approach. The companion
      paper reports observations suggesting that effects elicited by group II afferents
      may cooperate in the contraction-induced inhibition of motoneurons.

PMID- 8294955
TI  - Declining inhibition elicited in cat lumbar motoneurons by repetitive stimulation
      of group II muscle afferents.
AB  - 1. The aim of the present experiments was to verify whether group II inputs from
      gastrocnemius medialis (GM) muscle could elicit declining inhibitions similar to
      those observed during GM contractions in a variety of lumbar motoneurons of the
      cat spinal cord. Motoneurons were recorded intracellularly in chloralose- or
      pentobarbitone-anesthetized preparations during electrical stimulation of GM
      nerve with repetitive trains. 2. With strengths in the group I range, repetitive
      stimulation evoked the usual Ia excitation in homonymous motoneurons and
      excitatory postsynaptic potential (EPSP) amplitudes remained constant throughout
      the stimulation sequence. In synergic plantaris motoneurons lacking an excitatory
      connection with Ia afferents from GM, the same stimulation, kept at a constant
      strength throughout the stimulation sequence, elicited rapidly decreasing
      inhibitory potentials reminiscent of those evoked by GM contractions. 3. In
      motoneurons of pretibial flexors, quadriceps, and posterior biceps
      semitendinosus, the stimulation strength required to observe declining
      inhibitions resembling those produced by GM contractions was 4-8 times group I
      threshold, engaging group II in addition to group I fibers. 4. These results show
      that input from GM group II plus group I afferents can elicit inhibitory effects
      in a variety of motoneurons. Such observations support the hypothesis that
      messages from spindle secondary endings and/or nonspecific muscle receptors
      activated during contraction might contribute to the widespread inhibition caused
      by GM contractions. 5. Inasmuch as constant input in group II and group I
      afferents evoked declining inhibitory potentials, the origin of the decline must
      be central, which suggests that the rapid reduction of contraction-induced
      inhibitions also depended on a central mechanism.

PMID- 8294956
TI  - Fos-like immunoreactivity in the superficial medullary dorsal horn induced by
      noxious and innocuous thermal stimulation of facial skin in the rat.
AB  - 1. To examine further the ability of different classes of nociceptive and
      nonnociceptive primary afferent neurons to induce c-fos expression in central
      neurons, fos-like immunoreactivity was examined in the medullary dorsal horn
      (laminae I-IV) of the rat after facial application of a range of warming and
      cooling thermal stimuli. Urethan-anesthetized rats received 15 30-s thermal
      pulses (53, 50, 47, 41, 25, or 10 degrees C) applied to the vibrissal pad over a
      period of 30 min and were perfused 2 h after the end of stimulation. 2.
      Stimulation of 41 degrees C produced no significant increase in the number of fos
      LI-labeled cells in lamina I or II compared with control (35 degrees C) animals.
      3. Stimulation of 47 degrees C produced a significant increase in the number of
      fos-LI-labeled cells in both laminae I and II. Stimulation of 50 degrees C
      produced a significant increase in labeling, compared with that produced by 47
      degrees C, which was primarily in lamina II. Stimulation of 53 degrees C produced
      no further increase in the number of labeled cells, compared with that produced
      by 50 degrees C, in lamina I or II. 4. In the cooling direction, 25 degrees C
      produced a significant increase in labeling above control levels in both lamina I
      and II, whereas 10 degrees C produced a further increase compared with 25 degrees
      C, which was restricted to lamina I. 5. None of the stimuli produced a
      significant increase in labeling in laminae III-IV. 6. The results are
      interpreted as providing evidence that low-threshold cold receptors, high
      threshold cold receptors, and nociceptors are capable of inducing fos expression
      in dorsal horn neurons, whereas warm receptors are relatively ineffective. The
      results also provide evidence that neurons that receive input from C polymodal
      nociceptors are present in both laminae I and II, as are neurons that receive
      input from low-threshold cold receptors. Neurons that receive input from high
      threshold cold receptors, but not from low-threshold cold receptors, appear to be
      located preferentially in lamina I. The shape of the curve relating fos-LI
      labeling to stimulus temperature in the warming direction is consistent with the
      expected pattern of recruitment of primary afferent nociceptors.

PMID- 8294957
TI  - Effect of unilateral vestibular stimulation on histamine release from the
      hypothalamus of rats in vivo.
AB  - 1. We investigated the effect of unilateral vestibular stimulation on histamine
      release from the anterior hypothalamic area of urethan-anesthetized rats in vivo,
      using a brain microdialysis method coupled with high-performance liquid
      chromatography fluorometry. 2. The histamine release was increased to
      approximately 180% of the basal release by the electrical stimulation of the
      inner ear with 1 Hz, 500 microA, and 200 ms for 20 min. This effect was dependent
      on the current intensity. 3. Activation of the unilateral horizontal semicircular
      canal by middle ear irrigation for 15 min with 45 degrees C water increased the
      histamine release to approximately 200% of the basal release. 4. Irrigation of
      the middle ear with ice water for 15 min increased the histamine release to
      approximately 190% of the basal release. 5. The histamine release was not changed
      by the irrigation of the middle ear with 37 degrees C water and the irrigation of
      the auricle with ice water, which suggests that neither somatosensory stimulation
      to the middle ear nor nonspecific cold stress affects the histamine release. 6.
      All these findings suggest that the sensory mismatch signals induced by caloric
      stimulation and unilateral electrical vestibular stimulation activate the
      histaminergic neuron system in the brain.

PMID- 8294958
TI  - Computer simulations of the effects of different synaptic input systems on motor
      unit recruitment.
AB  - 1. The effects of four different synaptic input systems on the recruitment order
      within a mammalian motoneuron pool were investigated using computer simulations.
      The synaptic inputs and motor unit properties in the model were based as closely
      as possible on the available experimental data for the cat medial gastrocnemius
      pool and muscle. Monte Carlo techniques were employed to add random variance to
      the motor unit thresholds and forces and to sample the resulting recruitment
      orders. 2. The effects of the synaptic inputs on recruitment order depended on
      how they modified the range of recruitment thresholds established by differences
      in the intrinsic current thresholds of the motoneurons. Application of a uniform
      synaptic input to the pool (i.e., distributed equally to all motoneurons)
      resulted in a recruitment sequence that was quite stable even with the addition
      of large amounts of random variance. With 50% added random variance, the
      recruitment reversals did not exceed 8%. 3. The simulated monosynaptic input from
      homonymous Ia afferent fibers generated a twofold expansion of the range of
      recruitment thresholds beyond that attributed to the differences in the intrinsic
      current thresholds. The Ia input generated a small reduction in the number of
      recruitment reversals due to random variance (6% reversals at 50% random
      variance). The simulated monosynaptic vestibulospinal input generated a twofold
      compression of the range of recruitment thresholds that exerted a modest increase
      in the number of recruitment reversals (12% reversals at 50% random variance). 4.
      In comparison with the modest effects of the two monosynaptic inputs, the
      simulated oligosynpatic rubrospinal excitatory input exerted a nine-fold
      compression in the recruitment threshold range that resulted in a recruitment
      sequence that was highly sensitive to random variance. With 50% added random
      variance, the sequence became nearly random (40% reversals). 5. Reciprocal Ia
      inhibition was simulated by a uniform distribution within the pool, but its
      effects on recruitment order were highly dependent on the distribution of the
      excitatory input. Reciprocal inhibition exerted only minor effects on recruitment
      order when combined with the Ia or vestibulospinal inputs. However, when the
      excitatory drive was supplied by the rubrospinal input, even small amounts of
      reciprocal inhibition were sufficient to completely reverse the normal
      recruitment sequence. 6. The simulated monosynaptic Ia input was highly effective
      in compensating for the disruptive effects of rubrospinal excitation on
      recruitment order. Even a small Ia bias combined with the rubrospinal excitation
      was sufficient to halve the effects of random variance and to restore the normal
      recruitment sequence in the presence of rather large amounts of reciprocal
      inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294959
TI  - Cerebellar ataxia and muscle spindle sensitivity.
AB  - 1. The cerebellum has long been known to participate in movement control. One of
      the enduring theories of cerebellar function is that it "tunes" and coordinates
      sensorimotor traffic in other parts of the CNS. In particular, it has been
      implicated in the control of the sensitivity of muscle spindle stretch receptors
      through the fusimotor system. 2. The stretch sensitivity of spindle primary
      endings can be varied approximately over a 10-fold range by fusimotor efferent
      action. For many years it has been believed that cerebellar dysfunction is
      associated with reduced drive to the fusimotor system and that this in turn
      causes hypotonia by reducing the reflex excitation of alpha-motoneurons by
      spindle afferents. 3. The data on which this hypothesis is based were obtained in
      anesthetized or decerebrate animals. Little direct information is available on
      animals or humans performing voluntary movements and exhibiting ataxia or other
      cerebellar symptoms. 4. We tested the hypothesis by recording from nine muscle
      spindle afferents in behaving cats before and during reversible inactivation of
      cerebellar interpositus and dentate nuclei. In normal cats fusimotor action
      varies with motor task, greatly altering spindle stretch sensitivity. We
      investigated whether this same range of task-related sensitivity manifested
      itself during ataxia. 5. We found that the full range of spindle sensitivity was
      still present during ataxia. We therefore conclude that the cerebellar nuclei
      studied are not primarily responsible for fusimotor control, nor is the ataxia
      primarily caused by disordered proprioceptive sensitivity.

PMID- 8294960
TI  - Posttetanic hyperpolarization produced by electrogenic Na(+)-K+ pump in lizard
      axons impaled near their motor terminals.
AB  - 1. The hyperpolarization that follows tetanic stimulation was recorded intra
      axonally from the internodal region of intramuscular myelinated motor axons. 2.
      The peak amplitude of the posttetanic hyperpolarization (PTH) that followed
      stimulation at 20-100 Hz for < or = 35 s increased with increasing train
      duration, reaching a maximum of 22 mV. PTH decayed over a time course that
      increased from tens to hundreds of seconds with increasing train duration. For a
      given frequency of stimulation the time integral of PTH was proportional to the
      number of stimuli in the train, averaging 3-4 mV.s per action potential. 3.
      Ouabain (0.1-1 mM) and cyanide (1 mM) depolarized the resting potential and
      abolished PTH. Tetanic stimulation in ouabain was followed by a slowly decaying
      depolarization (probably due to extra-axonal K+ accumulation) whose magnitude and
      duration increased as the duration of the train increased. 4. Axonal input
      resistance showed no consistent change during PTH in normal solution but
      increased during PTH in the presence of 3 mM Cs+ (which blocks axonal inward
      rectifier currents). 5. PTH was abolished when bath Na+ was replaced by Li+ or
      choline. PTH persisted after removal of bath Ca2+ and addition of 2 mM Mn2+. 6.
      Removal of bath K+ abolished the PTH recorded after brief stimulus trains and
      greatly reduced the duration of PTH recorded after longer stimulus trains. 7. A
      brief application of 10 mM K+, which normally depolarizes axons, produced a
      ouabain-sensitive hyperpolarization in axons bathed in K(+)-free solution. 8.
      These observations suggest that in these myelinated axons PTH is produced mainly
      by activation of an electrogenic Na(+)-K(+)-ATPase, rather than by changes in K+
      permeability or transmembrane [K+] gradients. This conclusion is supported by
      calculations showing agreement between estimates of Na+ efflux/impulse based on
      PTH measurements and estimates of Na+ influx/impulse based on nodal voltage-clamp
      measurements. Pump activity also appears to contribute to the resting potential.
      9. The stimulus intensity required to initiate a propagating action potential
      increased during PTH but decreased during the posttetanic depolarization recorded
      in ouabain. Thus changes in axonal excitability after tetanic stimulation
      correlate with changes in the posttetanic membrane potential. 10. Action
      potentials that propagated during PTH had a larger peak amplitude and were
      followed by a larger and longer depolarizing afterpotential than action
      potentials elicited at the resting potential. This enhancement of the
      depolarizing afterpotential is consistent with previous reports of an increased
      superexcitable period after action potentials evoked during PTH.

PMID- 8294961
TI  - Modeling simple-cell direction selectivity with normalized, half-squared, linear
      operators.
AB  - 1. A longstanding view of simple cells is that they sum their inputs linearly.
      However, the linear model falls short of a complete account of simple-cell
      direction selectivity. We have developed a nonlinear model of simple-cell
      responses (hereafter referred to as the normalization model) to explain a larger
      body of physiological data. 2. The normalization model consists of an underlying
      linear stage along with two additional nonlinear stages. The first is a half
      squaring nonlinearity; half-squaring is half-wave rectification followed by
      squaring. The second is a divisive normalization non-linearity in which each
      model cell is suppressed by the pooled activity of a large number of cells. 3. By
      comparing responses with counterphase (flickering) gratings and drifting
      gratings, researchers have demonstrated that there is a nonlinear contribution to
      simple-cell responses. Specifically they found 1) that the linear prediction from
      counterphase grating responses underestimates a direction index computed from
      drifting grating responses, 2) that the linear prediction correctly estimates
      responses to gratings drifting in the preferred direction, and 3) that the linear
      prediction overestimates responses to gratings drifting in the nonpreferred
      direction. 4. We have simulated model cell responses and derived mathematical
      expressions to demonstrate that the normalization model accounts for this
      empirical data. Specifically the model behaves as follows. 1) The linear
      prediction from counterphase data underestimates the direction index computed
      from drifting grating responses. 2) The linear prediction from counterphase data
      overestimates the response to gratings drifting in the nonpreferred direction.
      The discrepancy between the linear prediction and the actual response is greater
      when using higher contrast stimuli. 3) For an appropriate choice of contrast, the
      linear prediction from counterphase data correctly estimates the response to
      gratings drifting in the preferred direction. For higher contrasts the linear
      prediction overestimates the actual response, and for lower contrasts the linear
      prediction underestimates the actual response. 5. In addition, the normalization
      model is qualitatively consistent with data on the dynamics of simple-cell
      responses. Tolhurst et al. found that simple cells respond with an initial
      transient burst of activity when a stimulus first appears. The normalization
      model behaves similarly; it takes some time after a stimulus first appears before
      the model cells are fully normalized. We derived the dynamics of the model and
      found that the transient burst of activity in model cells depends in a particular
      way on stimulus contrast. The burst is short for high-contrast stimuli and longer
      for low-contrast stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294962
TI  - Primary afferent depolarization of muscle afferents elicited by stimulation of
      joint afferents in cats with intact neuraxis and during reversible spinalization.
AB  - 1. In the anesthetized and artificially ventilated cat, stimulation of the
      posterior articular nerve (PAN) with low strengths (1.2-1.4 x T) produced a small
      negative response (N1) in the cord dorsum of the lumbosacral spinal cord with a
      mean onset latency of 5.2 ms. Stronger stimuli (> 1.4 x T) produced two
      additional components (N2 and N3) with longer latencies (mean latencies 7.5 and
      15.7 ms, respectively), usually followed by a slow positivity lasting 100-150 ms.
      With stimulus strengths above 10 x T there was in some experiments a delayed
      response (N4; mean latency 32 ms). 2. Activation of posterior knee joint nerve
      with single pulses and intensities producing N1 responses only, usually produced
      no dorsal root potentials (DRPs), or these were rather small. Stimulation with
      strengths producing N2 and N3 responses produced distinct DRPs. Trains of pulses
      were clearly more effective than single pulses in producing DRPs, even in the low
      intensity range. 3. Cooling the thoracic spinal cord to block impulse conduction,
      increased the DRPs and the N3 responses produced by PAN stimulation without
      significantly affecting the N2 responses. Reversible spinalization also increased
      the DRPs produced by stimulation of cutaneous nerves. In contrast, the DRPs
      produced by stimulation of group I afferents from flexors were reduced. 4.
      Conditioning electrical stimulation of intermediate and high-threshold myelinated
      fibers in the PAN depressed the DRPs produced by stimulation of group I muscle
      and of cutaneous nerves. 5. Analysis of the intraspinal threshold changes of
      single Ia and Ib fibers has provided evidence that stimulation of intermediate
      and high threshold myelinated fibers in the posterior knee joint nerve inhibits
      the primary afferent depolarization (PAD) of Ia fibers, and may either produce
      PAD or inhibit the PAD in Ib fibers, in the same manner as stimulation of
      cutaneous nerves. In 7/16 group I fibers the inhibition of the PAD was increased
      during reversible spinalization. 6. The results obtained suggest that
      intermediate and high-threshold myelinated fibers in the PAN have the same
      actions on Ia and Ib fibers as intermediate and high-threshold cutaneous
      afferents and may therefore be considered as belonging to the same functional
      system. They further indicate that in anesthetized preparations the pathways
      mediating the PAD of group I fibers, as well as the pathways mediating the
      inhibition of the PAD, may be subjected to a descending control that is removed
      by spinalization.

PMID- 8294963
TI  - Morphology and topography of identified primary afferents in trigeminal subnuclei
      principalis and oralis.
AB  - 1. Intra-axonal recording, receptive field mapping, horseradish peroxidase
      injection, cytochrome oxidase staining, and computer-assisted
      reconstruction/morphometric methods were used to elucidate the structure and
      topography of trigeminal primary afferent collaterals in the normal adult rat.
      Prior studies focused on trigeminal brain stem subnuclei interpolaris and
      caudalis. This work is extended here to the remaining 2 subnuclei, principalis
      (PrV) and oralis (SpVo), where collaterals from 66 axons in 37 adult rats were
      studied. In nine rats, three to five axons were stained for within-nucleus
      comparisons of different fibers. Quantitative analyses were restricted to
      vibrissa sensitive fibers. 2. All of the axons conducted rapidly with small, low
      threshold receptive fields. The majority responded to vibrissa deflection (n =
      47); the remainder responded to guard hair deflection; gentle pressure applied to
      hairy skin, glabrous skin, lingual mucosa, or an incisor; or jaw movement. All
      descended in the trigeminal sensory root where some bifurcated into ascending and
      descending branches. Each well-stained fiber gave rise to transversely oriented
      collaterals in PrV and SpVo. 3. Within PrV and SpVo, fibers with differing
      adaptation properties and receptive fields had indistinguishable collateral
      morphologies. Arbors from single axons were rostrocaudally discontinuous, small
      relative to collaterals in subnuclei interpolaris and caudalis, circumscribed and
      topographically organized in a manner consistent with cytochrome oxidase and bulk
      labeled primary afferent staining patterns. In SpVo and caudal PrV, the map is
      inverted with the nose pointing medially. In rostral PrV, the map turns 90
      degrees such that the nose points dorsally. 4. Axons had different quantitative
      properties along the rostrocaudal axis of the trigeminal brain stem complex.
      Whereas arbors subtended similar transverse areas throughout PrV and SpVo,
      collaterals in the rostral third of PrV had a relatively low bouton density.
      Arbors in the caudal two thirds of PrV had the highest bouton density. Arbors in
      SpVo tended to be more variable in size and shape than those of caudal PrV, and
      their bouton numbers were significantly lower than in PrV. 5. In PrV, arbors were
      largely confined to somatotopically corresponding cytochrome oxidase patches,
      precluding significant overlap of neighboring whisker projections. In SpVo,
      termination sites were not as strictly confined and numerous examples of within-
      and between-row overlap were obtained for whisker afferents in cases where
      multiple axons were stained.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294964
TI  - Responses of medullary raphe neurons to electrical and chemical activation of
      vagal afferent nerve fibers.
AB  - 1. Various intensities, frequencies, and pulse widths of electrical stimulation
      of vagal afferent fibers were used to assess the responses of 87 medullary raphe
      neurons to vagal afferent fiber input in pentobarbital sodium-anesthetized,
      barodenervated paralyzed cats. Thirty-seven neurons were antidromically activated
      from the T2-T3 segments of the thoracic spinal cord, and 40 neurons could not be
      antidromically activated. Neurons were located in the nucleus raphe magnus (79%)
      and the nucleus raphe obscurus (15%). The remaining 6% of the neurons were not
      found; however, their locations were comparable in depth and position on the
      midline with other neurons in the same animals whose locations were identified.
      2. The responses of 60 neurons to electrical stimulation of vagal afferent fibers
      were classified as excitatory (38%), inhibitory (24%), or mixed, (7%). The mixed
      responses were characterized by excitation at one frequency or intensity and
      inhibition at another frequency or intensity. The remaining 27 neurons did not
      clearly respond. 3. The excitatory responses to electrical stimulation of the
      cervical vagus nerve were intensity and frequency dependent. Inhibitory responses
      were frequency dependent at lower frequencies of stimulation and both frequency
      and intensity dependent at higher frequencies. The mixed responses were frequency
      dependent. Overall, longer pulse widths produced significantly greater responses
      than shorter pulse widths. 4. Thirty-three neurons were tested for responses to
      chemical stimulation of vagal afferents with intra-atrial injections of three
      doses of veratridine. Twenty-one percent were excited, 55% were inhibited, and 6%
      had mixed responses. For the mixed responses, excitation occurred at one dose and
      inhibition at another. The remaining 18% of the neurons were unresponsive to
      veratridine. The excitatory responses were dose dependent, but the inhibitory
      responses were not. Three doses of phenybiguanide (PBG) were also used to
      chemically activate vagal afferents in 27 neurons. Eleven percent were excited,
      44% were inhibited, and 4% had mixed responses. The remaining 41% were
      unresponsive to PBG. The excitatory and inhibitory responses were dose dependent.
      5. When comparing responses in projection and nonprojection neurons, inhibition
      was seen significantly more often in projection neurons and excitation in
      nonprojection neurons. Sixty-three percent of the neurons inhibited by electrical
      stimulation were raphespinal neurons, and 78% of the neurons excited by vagal
      stimulation were nonprojection neurons. Similar observations were made with the
      responses to chemical activation of the vagus. 6. Neurons with lower spontaneous
      discharge rates were more often excited by vagal stimulation and neurons with
      higher rates were more often inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294965
TI  - Generation and propagation of epileptiform discharges in a combined entorhinal
      cortex/hippocampal slice.
AB  - 1. The development of epileptiform discharges in response to tetanic stimulation
      of the Schaeffer collaterals was studied by using extracellular field potential
      recordings in CA1, CA3, dentate gyrus, and entorhinal cortex and intracellular
      recordings in CA1 neurons in rat hippocampal-parahippocampal slices, which were
      cut so as to maintain reciprocal connections between entorhinal cortex and
      hippocampus in vitro. 2. The first type of epileptiform discharge to develop was
      an immediate afterdischarge, which grew in duration and amplitude with repeated
      stimulation trains at 10-min intervals, until it plateaued after five to nine
      trains at 40-s duration, on average. This afterdischarge, when fully developed,
      consisted of an early, high frequency tonic component, followed by a later, lower
      frequency clonic component. Fully developed primary afterdischarges were all-or
      none, in that they had a definite threshold, and varied little in amplitude or
      duration when activated by threshold or suprathreshold stimulation. The primary
      discharge could be recorded simultaneously throughout the hippocampal
      parahippocampal slice, providing evidence for the intact reciprocal connections
      between hippocampus and entorhinal cortex. Intracellular recordings in CA1
      neurons revealed that during the tonic phase of the afterdischarge, neurons were
      depolarized by 15-30 mV and gradually repolarized during the clonic component. 3.
      After full development of the primary afterdischarge, a delayed secondary
      epileptiform discharge began to appear after five to nine stimulation trains.
      This late discharge began 2-5 min after the stimulation train and progressed in
      amplitude and duration with repeated stimulation, in some cases to 2-3 h long
      self-sustained epileptiform discharges. Like the primary afterdischarge, the
      secondary discharge could be recorded simultaneously throughout the hippocampal
      parahippocampal slice, and individual bursts comprising the secondary discharge
      occurred at earliest latency in the dentate gyrus, followed by activation in CA3,
      CA1, and finally in the entorhinal cortex. Intracellular recordings in CA1
      neurons established that the secondary discharge occurred without an accompanying
      depolarization. Rather, it appeared as synaptic bursts developing in an
      escalating frequency barrage, initiated 2-5 min after the primary afterdischarge.
      4. Lesioning studies were conducted to begin determining the site of origin of
      the secondary epileptiform discharge. After appearance of the secondary
      discharge, the mossy fibers were cut. This lesion abolished the secondary
      discharge but did not block the primary afterdischarge. Moving the stimulating
      electrodes from the Schaeffer collaterals to the mossy fibers proximal to the cut
      reestablished a truncated secondary discharge. In a second lesioning experiment,
      a cut was made through the subicular region of the hippocampal-parahippocampal
      slice before the onset of stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294966
TI  - Tonotopic and functional organization in the auditory cortex of the big brown
      bat, Eptesicus fuscus.
AB  - 1. In Eptesicus the auditory cortex, as defined by electrical activity recorded
      from microelectrodes in response to tone bursts, FM sweeps, and combinations of
      FM sweeps, encompasses an average cortical surface area of 5.7 mm2. This area is
      large with respect to the total cortical surface area and reflects the importance
      of auditory processing to this species of bat. 2. The predominant pattern of
      organization in response to tone bursts observed in each cortex is tonotopic,
      with three discernible divisions revealed by our data. However, although cortical
      best-frequency (BF) maps from most of the individual bats are similar, no two
      maps are identical. The largest division contains an average of 84% of the
      auditory cortical surface area, with BF tonotopically mapped from high to low
      along the anteroposterior axis and is part of the primary auditory cortex. The
      medium division encompasses an average of 13% of the auditory cortical surface
      area, with highly variable BF organization across bats. The third region is the
      smallest, with an average of only 3% of auditory cortical surface area and is
      located at the anterolateral edge of the cortex. This region is marked by a
      reversal of the tonotopic axis and a restriction in the range of BFs as compared
      with the larger, tonotopically organized division. 3. A population of cortical
      neurons was found (n = 39) in which each neuron exhibited two BF threshold minima
      (BF1 and BF2) in response to tone bursts. These neurons thus have multipeaked
      frequency threshold tuning curves. In Eptesicus the majority of multipeaked
      frequency-tuned neurons (n = 27) have threshold minima at frequencies that
      correspond to a harmonic ratio of three-to-one. In contrast, the majority of
      multipeaked neurons in cats have threshold minima at frequencies in a ratio of
      three-to-two. A three-to-one harmonic ratio corresponds to the "spectral notches"
      produced by interference between overlapping echoes from multiple reflective
      surfaces in complex sonar targets. Behavioral experiments have demonstrated the
      ability of Eptesicus to use spectral interference notches for perceiving target
      shape, and this subpopulation of multipeaked frequency-tuned neurons may be
      involved in coding of spectral notches. 4. The auditory cortex contains delay
      tuned neurons that encode target range (n = 99). Most delay-tuned neurons respond
      poorly to tones or individual FM sweeps and require combinations of FM sweeps.
      They are combination sensitive and delay tuned.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294967
TI  - Synchronization of motor-unit firings in several human muscles.
AB  - 1. Synchronization of concurrently active motor-unit firings was studied in six
      human muscles performing isometric constant-force contractions at 30% of the
      maximal level. The myoelectric signal was detected with a quadrifilar needle
      electrode and was decomposed into its constituent motor-unit action-potential
      trains with the Precision Decomposition technique, whose accuracy has been proven
      previously. 2. Synchronization was considered as the tendency of two motor units
      to fire at fixed time intervals with respect to each other more often than would
      be expected if the motor units fired independently. A rigorous statistical
      technique was used to measure the presence of peaks in the cross-interval
      histogram of pairs of motor-unit action-potential trains. The location of the
      center of peak as well as their width and amplitude were measured. A synch index
      was developed to measure the percentage of firings that were synchronized. The
      percentage of concurrently active motor-unit pairs that contained synchronized
      firings was measured. 3. Synchronization of motor-unit firings was observed to
      occur in two modalities. The short-term modality was seen as a peak in the cross
      interval histogram centered about zero-time delay (0.5 +/- 2.9 ms, mean +/- SD)
      and with an average width of 4.5 +/- 2.5 ms. The long-term modality was seen as a
      peak centered at latencies ranging from 8 to 76 ms. On the average, the peaks of
      the long-term synchronization were 36% lower but had approximately the same width
      as the peaks for the short-term synchronization. Short-term synchronization was
      seen in 60% of the motor-unit paris, whereas long-term synchronization was seen
      in 10% of the pairs. 4. Short-term synchronization occurred in bursts of
      consecutive firings, ranging in number from 1 to 10, with 91% of all synchronized
      firing occurring in groups of 1 or 2; and the bursts of discharges appeared at
      sporadic times during the contraction. 5. The amount of synchronization in motor
      unit pairs was found to be low. In the six muscles that were tested, an average
      of 8.0% of all the firings were short-term synchronized, and an average of 1.0%
      were long-term synchronized. The synch index was statistically indistinguishable
      (P = 0.07-0.89) among the different muscles and among 9 of the 11 subjects
      tested. 6. Sixty percent of concurrently active motor-unit pairs displayed short
      term synchronization, 10% of the pairs displayed long-term synchronization, and
      8% displayed both modalities.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294968
TI  - The time course of direction-selective adaptation in simple and complex cells in
      cat striate cortex.
AB  - 1. Responses of single cortical neurons in area 17 of anesthetized cats were
      recorded in response to prolonged stimulation with a patch of drifting square
      wave grating. 2. During adaptation in the preferred direction, all neurons showed
      some reduction in response to motion in the stimulated direction and most showed
      some reduction in the opposite, nonstimulated direction. 3. For complex cells,
      the time course of response decrement in both the stimulated and nonstimulated
      directions was exponential, with an average time constant of 5 s. Response
      recovery was also exponential but significantly slower, with time constants of 8
      and 13 s in the stimulated and nonstimulated directions, respectively. 4. For
      simple cells the dynamics of the adaptation effect depended on the direction of
      testing. In the nonstimulated direction the time course of the change in
      sensitivity was similar to that of complex cells. In the stimulated direction
      during both the adaptation and recovery periods, simple cells showed an initial
      rapid exponential change on the order of a few seconds that was followed by a
      more gradual exponential change. 5. During prolonged stimulation in the
      nonpreferred direction, there was less overall change in sensitivity. For some
      neurons the change in sensitivity during adaptation and recovery was exponential,
      with a short time constant for both simple and complex cells and for stimulated
      and nonstimulated directions. Other neurons showed no change in sensitivity in
      either direction and a few neurons showed facilitation during the adaptation
      period. 6. There appears to be a rapid general or nonspecific process, which may
      be related to contrast gain control, underlying motion adaptation in striate
      cortical neurons. An additional slow, direction-selective process is revealed
      when simple but not complex cells are stimulated in the preferred direction. We
      suggest that this latter type of adaptation is a key feature underlying the
      perceptual motion aftereffect.

PMID- 8294969
TI  - A selective LTP of NMDA receptor-mediated currents induced by anoxia in CA1
      hippocampal neurons.
AB  - 1. The possibility of long-lasting modifications of glutamatergic responses after
      anoxic-aglycemic (AA) episodes was investigated in CA1 hippocampal neurons of
      adult slices. Bicuculline (10 microM) was continuously bath applied to block
      GABAA receptor-mediated currents. AA episodes were induced by brief (1.30-3 min)
      perfusions with a glucose free artificial-cerebro-spinal-fluid (ACSF) saturated
      with 95% N2-5% CO2. 2. In presence of (0.6 mM) Mg2+ and a low concentration of
      the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1 microM), the Schaffer
      collateral field EPSPs consisted of an early AMPA receptor-mediated component and
      a late N-methyl-D-aspartate (NMDA) receptor-mediated component. The former was
      blocked by (10 microM) CNQX and the latter by (50) microM D-2-amino-5
      phosphonovalerate (D-APV). The AA episode induced a selective long-term
      potentiation (LTP) of the NMDA receptor-mediated component [+70 +/- 13% (mean +/-
      SE), P < or = 0.008, n = 9] without affecting significantly the AMPA receptor
      mediated component (+2 +/- 4, P < or = 0.86 n = 9). This selective LTP is due to
      an enhanced efficacy of synaptic transmission and will be referred to as anoxic
      LTP. 3. In slices perfused with an ACSF containing a physiological concentration
      of (1.3 mM) Mg2+ and no CNQX, the intracellularly recorded excitatory
      postsynaptic potential (EPSP) was mixed (AMPA/NMDA) at -65 mV and exclusively
      mediated by AMPA receptors at -100 mV. At -65 mV, the AA episode induced a
      persistent potentiation of the EPSP (peak amplitude potentiated by 43 +/- 6%, P <
      or = 0.008, n = 9, 1 h after return to control ACSF). This potentiated component
      of the EPSP was fully sensitive to (50 microM) D-APV. The CNQX-sensitive AMPA
      receptor-mediated component was not affected by the AA episode (-5.7 +/- 6%, P <
      or = 0.123, n = 9). Furthermore, at -100 mV a large APV-sensitive component
      appeared after the AA episode (+58 +/- 18% of the peak amplitude, P < or = 0.018,
      n = 9). Therefore, the AA episode induced a selective LTP of the NMDA receptor
      mediated component of the EPSP. 4. A robust LTP (+50.0 +/- 7.5%, P < or = 0.008,
      n = 12) of the NMDA receptor-mediated intracellular EPSP was also observed when
      AMPA receptors were fully and continuously blocked by (15 microM) CNQX.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8294970
TI  - Signal delay and input synchronization in passive dendritic structures.
AB  - 1. A novel approach for analyzing transients in passive structures called "the
      method of moments" is introduced. It provides, as a special case, an analytic
      method for calculating the time delay and speed of propagation of electrical
      signals in any passive dendritic tree without the need for numerical simulations.
      2. Total dendritic delay (TD) between two points (y, x) is defined as the
      difference between the centroid (the center of gravity) of the transient current
      input, I, at point y[tI(y)] and the centroid of the transient voltage response,
      V, at point x [tV(x)]. The TD measured at the input points is nonzero and is
      called the local delay (LD). Propagation delay, PD(y, x), is then defined as
      TD(y, x)--LD(y) whereas the net dendritic delay, NDD(y, 0), of an input point, y,
      is defined as TD(y, 0) - LD(0), where 0 is the target point, typically the soma.
      The signal velocity at a point x0 in the tree, theta(x0), is defined as
      [1/(dtv(x)/dx)[x = x0. 3. With the use of these definitions, several properties
      of dendritic delay exist. First, the delay between any two points in a given tree
      is independent of the properties (shape and duration) of the transient current
      input. Second, the velocity of the signal at any given point (y) in a given
      direction from (y) does not depend on the morphology of the tree "behind" the
      signal, and of the input location. Third, TD(y, x) = TD(x, y), for any two
      points, x, y. 4. Two additional properties are useful for efficiently calculating
      delays in arbitrary passive trees. 1) The subtrees connected at the ends of any
      dendritic segment can each be functionally lumped into an equivalent isopotential
      R-C compartment. 2) The local delay at any given point (y) in a tree is the mean
      of the local delays of the separate structures (subtrees) connected at y,
      weighted by the relative input conductance of the corresponding subtrees. 5.
      Because the definitions for delays utilize difference between centroids, the
      local delay and the total delay can be interpreted as measures for the time
      window in which synaptic inputs affect the voltage response at a target/decision
      point. Large LD or TD is closely associated with a relatively wide time window,
      whereas small LD or TD imply that inputs have to be well synchronized to affect
      the decision point. The net dendritic delay may be interpreted as the cost (in
      terms of delay) of moving a synapse away from the target point.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8294971
TI  - Thalamic VPM nucleus in the behaving monkey. III. Effects of reversible
      inactivation by lidocaine on thermal and mechanical discrimination.
AB  - 1. The present study evaluates the necessity of the ventroposterior medial
      thalamic nucleus (VPM) for discrimination of the intensity of noxious heating,
      innocuous cooling, and innocuous tactile (airpuff) stimulation of the maxillary
      skin. 2. Two rhesus monkeys were trained to detect small differences (< 1.0
      degrees C) in the intensity of noxious heat (near 46 degrees C) and innocuous
      cold (near 30 degrees C) as well as differences in the force of an airpuff
      applied to the skin over the maxilla. As a control the monkeys also detected
      small differences in the intensity of a white light. Lidocaine hydrochloride (2%)
      was microinjected into regions of thalamus where single-unit recordings had
      identified neuronal responses to the noxious heating and/or cooling stimuli. The
      effectiveness of the anesthetic blockade was monitored by multiunit recordings
      using microelectrodes positioned 1-3 mm from the orifice of the injection
      cannula. The monkey's ability to detect near-threshold changes in stimulus
      intensity was compared before and after each injection. 3. During six
      experimental sessions, single injections of 1-4 microliters lidocaine near the
      dorsomedial border of VPM did not significantly alter the monkey's ability to
      detect small changes in the intensity of noxious heat, cool, airpuff, or visual
      stimuli despite neurophysiological evidence that spontaneous neuronal activity
      was blocked within parts of VPM. 4. During three experiments, dual simultaneous
      microinjections of lidocaine (delivered through 2 microcannulae separated by
      approximately 1 mm) resulted in profound deficits in noxious heat discrimination,
      with lesser deficits in cool and airpuff discrimination; visual discrimination
      was never altered. Monitoring of adjacent microelectrodes revealed that although
      activity ventral to the injection sites was blocked, activity in medial thalamic
      nuclei, implicated in nociceptive processing, was probably not altered by these
      injections. 5. These data suggest that VPM is important for the perception of
      noxious and innocuous thermal stimuli as well as for the perception of tactile
      stimuli. However, considering the ineffectiveness of small single microinjections
      of lidocaine, it appears that some critical proportion of VPM must be inactivated
      to disrupt thermal or tactile discrimination, possibly because of overlapping
      receptive field properties of neurons in different areas of the nucleus.

PMID- 8294972
TI  - Neuronal specification of direction and distance during reaching movements in the
      superior precentral premotor area and primary motor cortex of monkeys.
AB  - 1. Single-unit neuronal activity was recorded in the primary motor and superior
      precentral premotor areas of two rhesus monkeys during an arm reaching task. The
      task involved moving a cursor displayed on a video terminal using a draftsman's
      arm-type manipulandum. From a centrally located start box the animal was required
      to move to 1 of 48 target boxes at eight different directions (0-360 degrees in
      45 degrees intervals) and six distances (1.4-5.4 cm in 0.8-cm increments). Both
      direction and distance for the upcoming movement were unpredictable. 2. The
      activity of 197 arm movement-related cells was recorded and evaluated for each of
      the 48 targets. Histological examination showed the cells to be primarily in the
      primary motor cortex or in the premotor area around the superior precentral
      sulcus. Each cell's discharge was aligned on movement onset and averaged over
      five trials for each target. Movement kinematics including hand path velocity
      were also determined. The task time was divided into three epochs, a premovement
      period (PT), a movement period (MT), and total time (TT = PT+MT). For each epoch
      the average firing was correlated with the direction and distance of the movement
      using various regression procedures. 3. An analysis of variance (ANOVA) showed
      that the majority of neurons were modulated significantly by movement direction
      in each of the three time periods, PT (73.7%), MT (68.3%), and TT (78.5%). The
      relationship of the firing to direction was fit to a cosine tuning function for
      each significantly modulated cell. In 86.3% of the cells the firing was
      correlated significantly with a cosine function of movement direction in TT. A
      cell's preferred direction varied little for different movement distances. The
      mean difference in preferred direction for the smallest possible change in
      distance (0.8 cm) was 12.8 +/- 11.4 degrees (SD) and 17.1 +/- 14.7 degrees for
      the largest change in distance (4.0 cm). 4. Correlation analysis revealed that
      the activity of the majority of cells was modulated significantly by distance
      along at least one direction in each of the three time periods, PT (46.8%), MT
      (68.8%), and TT (67.7%). Subsequently, a univariate linear regression model was
      used to quantify a cell's discharge as a function of distance. For the
      regressions of firing with distance with a statistically significant correlation
      (r > 0.8), the mean slope was 3.59 +/- 0.17 spikes.s-1.cm-1 for the total time.
      The existence of a significant distance modulation was not invariably correlated
      with a cell's preferred movement direction.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294973
TI  - Development of metabolic activity patterns in the somatosensory cortex of cats.
AB  - 1. The development of cortical responses to somatic stimulation was studied in
      kittens 2-5 wk of age using the 2-deoxyglucose (2DG) technique. During the 2DG
      experiment each kitten received an innocuous intermittent vertical displacement
      stimulus to the forepaw. 2. The pattern of metabolic activity was substantially
      different in young animals compared with adults. In the individual
      autoradiographs of the 2-wk-old kittens stimulus-evoked 2DG uptake in primary
      somatosensory cortex was localized to a small spot in the upper portion of the
      cortex, whereas in the adult the label extended vertically through the cortical
      layers and appeared more column-like. Individual patches of label were
      substantially smaller and less dense in young animals. Over a period of several
      weeks the evoked activity evolved to the more extensive adult pattern. The 2DG
      uptake displayed a mature distribution by approximately 4-5 wk of age. During
      this period, the cortical architecture also evolved from an immature to a mature
      arrangement. 3. The evoked activity was reconstructed into two-dimensional maps;
      the distribution of label > or = 1.5 SD above background was considered to be
      stimulus related. In the adult, the pattern appeared as a strip or strips of
      increased metabolic activity that extended in the rostrocaudal direction for
      approximately 1 mm. In contrast, the activity pattern in animals 2-4 wk old was
      less discretely organized into "strips" and was more diffusely spread over
      several mms of somatosensory cortex. The two-dimensional pattern gradually
      coalesced into a more localized strip by approximately 4-5 wk of age. Although
      the pattern of label was more widespread in the young animals, the absolute
      distance of the spread of activity did not vary substantially, regardless of the
      age of the animal. 4. Other measurements regarding the distribution of activity
      at different ages indicate that the amount of cortex activated increases in
      absolute terms, although the percent of cortex activated by the stimulus
      decreases. The overall intensity of the 2DG uptake as measured on the two
      dimensional maps increases with age, as does the variability of the 2DG uptake; a
      wider range of intensity values is seen in the adult. Plots created from the
      individual two-dimensional reconstructions allowed a measure of "patch strength"
      at different ages. These histograms relate the most intense region of uptake in a
      given map to the spatial distribution of activity spreading in the medial and
      lateral directions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8294975
TI  - Loss of proprioception produces deficits in interjoint coordination.
AB  - 1. We analyzed the performance of a simple pantomimed gesture in 2 patients with
      large-fiber sensory neuropathy and 11 control subjects to determine how
      proprioceptive deafferentation disrupts unconstrained multijoint movements. Both
      patients had near-total loss of joint position, vibration, and discriminative
      touch sensation in the upper extremities. Muscle strength remained intact. 2.
      Subjects performed a gesture similar to slicing a loaf of bread. In this gesture,
      the hand first moves outward from the body, reverses direction sharply, and then
      moves back toward the body. Accurate performance requires precise coordination
      between the shoulder and elbow joints during movement reversals. Movements were
      performed under two conditions: with eyes open and with eyes closed. Three
      dimensional shoulder, elbow, wrist, and hand trajectories were recorded on a
      WATSMART system. 3. When control subjects performed the gesture with their eyes
      closed, their wrist trajectories were relatively straight and individual cycles
      of motion were planar. Movements reversed direction sharply, such that outward
      and inward portions of the wrist path were closely aligned. Corresponding to this
      spatial profile, the reversals in movement direction at the shoulder joint, from
      flexion to extension, and at the elbow joint, from extension to flexion, were
      synchronous. 4. In contrast, when deafferented patients performed the gesture
      with their eyes closed, their wrist trajectories were highly curved and
      individual cycles were severely nonplanar. The wrist paths showed a
      characteristic anomaly during the reversal in movement direction, when elbow
      joint movement became transiently locked. Correspondingly, the movement reversals
      at the shoulder and elbow joints were severely temporally decoupled. 5. When
      patients were able to view their limbs during performance of this gesture there
      was significant improvement in the linearity and planarity of movements. However,
      the patients remained unable to synchronize the movements at the shoulder and
      elbow joints to produce spatially precise wrist paths. 6. We conclude that loss
      of proprioception disrupts interjoint coordination and discuss the hypothesis
      that this interjoint coordination deficit results from a failure to control the
      interaction forces that arise between limb segments during multijoint movements.

PMID- 8294974
TI  - Inhibitory action of muscarinic agonists on neurons in the rat laterodorsal
      tegmental nucleus in vitro.
AB  - 1. The effects of the mixed cholinergic agonist carbachol and the muscarinic
      agonist methacholine (MCh) on neurons of the laterodorsal tegmental nucleus (LDT)
      were studied with the use of intracellular and whole-cell patch-clamp recordings
      in a rat brain stem slice preparation. 2. Neurons were classified into one of two
      categories on the basis of their intrinsic membrane properties: those that
      displayed a prominent low-threshold calcium burst (LTB, 60%) and those that did
      not exhibit such a burst (non-LTB, 40%). 3. Neurons from which recordings were
      obtained were filled with biocytin, visualized with Texas-red avidin, and
      identified as cholinergic or noncholinergic with NADPH-diaphorase histochemistry.
      Eighty percent of the LTB neurons that were processed in this manner were
      cholinergic, and 60% of the non-LTB neurons were cholinergic. 4. Carbachol
      elicited a membrane hyperpolarization associated with a decrease in input
      resistance in 95% of the cells tested. Under voltage clamp this response was
      shown to be due to an outward current that reversed near the equilibrium
      potential for potassium and displayed marked inward rectification. The
      conductance/voltage relationship was fit to the Boltzmann equation with a mean
      V1/2 = -73 +/- 4 (SD) mV and a mean k value of 10 +/- 4. The carbachol-evoked
      current was fully blocked by extracellular barium. 5. There was no significant
      effect of carbachol on the transient currents IA or IT. 6. The carbachol-evoked
      current was mimicked by the specific muscarinic agonist methacholine and blocked
      by high concentrations of the muscarinic receptor antagonist pirenzepine (IC50 =
      580 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8294976
TI  - Alteration of bursting properties in interneurons during locust flight.
AB  - 1. The contribution of bursting properties to the generation of the flight motor
      pattern was examined for two identified interneurons (interneurons 566 and 567)
      in the flight system of the locust Locusta migratoria by means of intracellular
      recording and stimulation techniques. These interneurons are important elements
      in transmitting proprioceptive information from the hindwing tegula to wing
      elevator motoneurons. 2. Offset currents injected into these neurons revealed
      that bursts are triggered in the intact flying animal by synaptic input from
      tegula afferents (n = 10). These bursts lead to an amplification of
      proprioceptive input that is crucial for the generation of the intact flight
      motor pattern. In the absence of afferent input the activity of these neurons
      remained subthreshold for triggering a burst. This explains why these neurons
      exhibit only weak rhythmic oscillations in deafferented animals. 3. The property
      of interneuron 566 to burst was conditional, always being expressed during flight
      (n = 14) and occurring only occasionally in the quiescent animal. In the absence
      of flight, stimulation of tegula afferents never evoked bursts in interneuron 566
      (n = 7) and depolarizing current pulses evoked weak bursts in only three of nine
      preparations. In 2 of 14 animals, bursting property of interneuron 566 was
      enhanced just after the termination of flight. 4. Variability in the bursting
      property was also found for interneuron 567. In the quiescent animal, tegula
      evoked compound excitatory postsynaptic potentials were not sufficient to trigger
      bursts (n = 3) but depolarizing current pulses evoked always weak rhythmic
      bursting activity (n = 4). This bursting property was also variable and in one
      animal we found long-lasting plateau potentials that could be evoked by current
      injection after flight was elicited several times. 5. The data presented
      demonstrate that the capacity to burst is conditional in the interneurons 566 and
      567. Bursting properties are always induced during flight and function to amplify
      proprioceptive pathways that are important for the generation of the intact
      flight motor pattern.

PMID- 8294977
TI  - Coding of odor molecules by mitral/tufted cells in rabbit olfactory bulb. II.
      Aromatic compounds.
AB  - 1. Recordings of extracellular spike responses were made from single
      mitral/tufted cells in the ventromedial region of the main olfactory bulb of
      urethan-chloralose-anesthetized rabbits. Using periodic artificial inhalations,
      the olfactory epithelium was stimulated with series of aromatic and aliphatic
      compounds systematically varying in molecular conformation. 2. Analysis of
      response specificity of single mitral/tufted cells for alkylbenzenes indicated
      that the length of the hydrocarbon side chain attached to the benzene ring plays
      a role in determining the specificity of excitatory spike responses. 3. For a
      panel of isomeric (ortho-, meta-, and para-positions) disubstituted benzenes,
      single mitral/tufted cells tended to be activated selectively by one or two
      specific structural isomer(s). For a panel that contained both alkylbenzenes and
      disubstituted benzenes, single mitral/tufted cells were activated by subsets of
      odor molecules having similar conformations. These observations suggest that the
      overall conformation of the aromatic compounds plays an important role in
      determining tuning specificity of individual mitral/tufted cells. 4. For a panel
      of monosubstituted benzenes with various functional groups, single mitral/tufted
      cells in the ventromedial region tended to be activated not only by molecules
      having a hydrocarbon side chain (alkylbenzenes), but also by those having a
      methoxy group (--O--CH3), a bromine (--Br), or a chlorine (--Cl). However, most
      of the neurons were not activated by those having an amino group (--NH2), a
      hydroxy group (--OH), nor a carboxyl group (--COOH). 5. Examination with an
      expanded panel of stimulus odor molecules that included both aromatic and
      aliphatic compounds indicated that single mitral/tufted cells show excitatory
      spike responses to a range of odor molecules (molecular receptive range) having
      similar conformations. Different mitral/tufted cells in the ventromedial region
      typically showed different molecular receptive ranges. 6. In mitral/tufted cells
      with relatively high spontaneous discharges, single neurons in the ventromedial
      region showed inhibitory responses to subsets of odor molecules in addition to
      the excitatory response to other subsets of odor molecules. The odor molecules
      that caused inhibitory responses in single mitral/tufted cells showed molecular
      conformations resembling each other. 7. The present results together with
      previous studies indicate that determination of the molecular receptive range
      properties (both excitatory extent and inhibitory extent) of single mitral/tufted
      cells is a useful method for characterizing individual bulbar neurons. These
      results further support the hypothesis that conformational parameters of ligand
      odor molecules play a key role in sensory processing in the main olfactory bulb.

PMID- 8294978
TI  - Activity of medial vestibulospinal tract cells during rotation and ocular
      movement in the alert squirrel monkey.
AB  - 1. Chronic unit and eye movement recording and microstimulation techniques were
      used to study the discharge properties of identified medial vestibulospinal tract
      (MVST) cells in the alert squirrel monkey. MVST cells were antidromically
      activated from the ventromedial funiculus at C1 and responded to orthodromic
      stimulation of the ipsilateral VIIIth nerve (Vi) at mono- or disynaptic
      latencies. Cell discharges were examined during imposed sinusoidal yaw rotation
      to activate horizontal semicircular canal afferents and during voluntary ocular
      pursuit and fixation of visual targets with the head held stationary. 2. MVST
      cells represented 15% (22 of 147 cells) of the population of horizontal canal
      related cells recorded in the vestibular nuclei. Twelve MVST cells were
      monosynaptically related to Vi; of these cells, 7 (58%) were characterized as
      ipsilateral eye and head velocity, having a discharge modulation related to the
      velocity of both ipsilaterally directed eye movement and yaw rotation, and 3 also
      had an ipsilateral eye position sensitivity. Most (8 of 10, 80%) MVST cells
      disynaptically related to Vi responded only to contralateral head velocity; the
      other 2 cells carried a combined contralateral head and ipsilateral eye movement
      signal. A pause or burst of discharge associated with fast or saccadic eye
      movements made in any direction was not present on the 22 MVST cells. 3. The MVST
      is an output pathway of the vestibular nuclei through which the labyrinth
      controls reflex head movements. The results show that MVST cells transmit the
      movement and position of eyes in orbit, with vestibular signals, to the cervical
      spinal cord and suggest that the MVST may play a dynamic role in voluntary gaze
      stabilization and eye/head tracking.

PMID- 8294979
TI  - Subthreshold oscillations of the membrane potential: a functional synchronizing
      and timing device.
AB  - 1. Subthreshold membrane potential oscillations have been observed in different
      types of CNS neurons. In this in vitro study, we examined the possible role of
      these oscillations by analyzing the responses of neurons from the inferior
      olivary nucleus to a combined stimulation of sine wave and synaptic potentials.
      2. A nonlinear summation of the sine wave and the synaptic potential occurred in
      olivary neurons; a superlinear summation occurred when the synaptic potential was
      elicited at the trough of the sine wave or during the rising phase. On the other
      hand, a less than linear summation occurred when the synaptic potentials were
      evoked during the falling phase of the wave. 3. Significant changes in the delay
      of the synaptic responses were observed. As a result of these changes, the
      maximum amplitude of the response occurred at the peak of the sine wave,
      regardless of the exact time of stimulation. The output of the neuron was
      therefore synchronized with the sine wave and depended only partly on the input
      phase. 4. These data demonstrate that neurons from the inferior olivary nucleus
      are capable of operating as accurate synchronizing devices. Moreover, by
      affecting the delay line, they act as a logic gate that ensures that the
      information will be added to the system only at given times.

PMID- 8294980
TI  - Possible network interactions indicated by bilaterally coherent fast rhythms in
      expiratory recurrent laryngeal nerve discharges.
AB  - 1. In a search for correlated fast rhythms in recurrent laryngeal (RL) expiratory
      (E) activities, we performed spectral and coherence analysis on bilateral RL
      nerve discharges in 54 midcollicular decerebrate, paralyzed cats. 2. Inspiratory
      (I) RL activities showed in almost all cases high-frequency oscillations (HFO,
      range 50-100 Hz) that were bilaterally coherent and also coherent to HFOs in
      phrenic (PHR) activities. In contrast, bilaterally coherent rhythms (range 24-54
      Hz) in RLE discharges were found in only a fraction of the cats (6/54); in the
      other cats (48/54) such coherences were absent even though the auto-spectra
      showed the presence of similar fast rhythms on the two sides. The bilateral RLE
      coherences were associated with increased amplitude and prolonged duration of RLE
      activity, such as occurred following removal of phasic pulmonary stretch receptor
      inputs by vagotomy or by no-inflation. 3. Thus, although coherent fast rhythms
      are uncommon in RLE discharges, their occurrence under some conditions indicates
      the presence of short-time-scale interactions between neurons involved in this
      activity. This suggests that such rhythms are a general feature of neural
      networks.

PMID- 8294981
TI  - Nuclear medicine practitioners evaluate their cost-effectiveness.

PMID- 8294983
TI  - Communications among nuclear medicine professionals: one approach to sharing
      information.

PMID- 8294982
TI  - Detection of deep venous thrombi and pulmonary embolus with technetium-99m-DD
      3B6/22 anti-fibrin monoclonal antibody Fab' fragment.
AB  - Technetium-99m-labeled anti-fibrin DD-3B6/22 Fab' monoclonal antibody fragments,
      which specifically target human cross-linked fibrin with high affinity, were
      evaluated in humans for safety and their capacity to detect deep vein thrombi and
      pulmonary embolism. METHODS: Twenty patients with proven deep-vein thrombosis,
      documented by contrast venography, or venous duplex scan, were injected with a
      600 MBq (0.5 mg) dose of antibody. Planar images of the lower limbs were recorded
      at 0, 2, 6 and 24 hr and chest scintigrams were recorded at 6 and 24 hr. RESULTS:
      All venography documented thrombus sites, calves, popliteal and femoral, were
      detected with the radioimmunoconjugate. For the venous duplex scan-proven
      thrombus sites, all except two calf thrombi in two patients with bilateral
      disease and other positive sites were detected. Five patients had bilateral deep
      vein thrombosis with multiple sites being visualized with the
      radioimmunoconjugate in the calf, popliteal and femoral regions. One case of
      pulmonary embolus was also definitively demonstrated. Documented thrombus sites
      were detected at 2 and 6 hr postinjection. Nineteen patients were on heparin. No
      adverse reactions to the injected dose were observed and one low titer human anti
      mouse antibody response may have occurred. CONCLUSION: The results indicate that
      99mTc-DD-3B6/22 Fab' has potential for noninvasive detection of deep-vein
      thrombosis and pulmonary embolism.

PMID- 8294984
TI  - Thrombus-specific imaging: approaching the elusive goal.

PMID- 8294985
TI  - Impaired lung epithelial permeability in diabetics detected by technetium-99m
      DTPA aerosol scintigraphy.
AB  - The clearance of inhaled 99mTc-diethyl triaminepentaacetic acid (DTPA) aerosol
      from the lungs is used as an index of lung epithelial permeability. We
      investigated the involvement of the lung in diabetic patients using 99mTc-DTPA
      aerosol scintigraphy. METHODS: A total of 33 diabetic patients were studied.
      Thirteen had complications such as retinopathy and/or nephropathy (Group A) and
      20 were without complications (Group B). As a control group, 20 healthy
      nonsmokers were studied. Dynamic scintigrams (2 min/frame, up to 30 min) were
      obtained following inhalation of 99mTc-DTPA through a radioaerosol delivery
      system. Time-activity curves were obtained and half-time (T1/2) of DTPA was
      measured from the curves. RESULTS: The mean T1/2 values (min +/- s.d.) were
      calculated to be 133.05 +/- 46.97, 93.67 +/- 21.23, 91.97 +/- 18.21 (Group A,
      Group B and controls, respectively). The mean T1/2 of Group A was significantly
      longer than controls (p < 0.005) and than that of Group B (p < 0.005) indicating
      decreased epithelial permeability. No such statistical difference was detected
      between Group B and controls (p > 0.05). CONCLUSION: The lung is a target organ
      in diabetes and lung involvement is closely related to other vascular
      complications. The presence of lung involvement can be readily detected by 99mTc
      DTPA aerosol scintigraphy.

PMID- 8294986
TI  - Technetium-99m-DTPA aerosol to measure alveolar-capillary membrane permeability.

PMID- 8294987
TI  - High-resolution technetium-99m-HMPAO SPECT in patients with probable Alzheimer's
      disease: comparison with fluorine-18-FDG PET.
AB  - SPECT studies of regional cerebral perfusion with a high-resolution system were
      compared to PET studies of regional cerebral glucose utilization (rCMRglc) in 21
      patients with probable Alzheimer's disease (AD). Ten normal subjects were also
      evaluated with SPECT and 10 with PET. METHODS: rCMRglc (for PET) and counts (for
      SPECT) in the associative cortices were normalized to the average rCMRglc, and
      counts in the calcarine cortex and basal ganglia were considered as a "reference
      area" to obtain a ratio. The ratio differences between patients and controls were
      tested with ANOVA performed separately for PET and SPECT. RESULTS: The difference
      between probable AD patients and controls was significant for both PET (p <
      0.00001) and SPECT (p < 0.005); this difference was significant for the frontal,
      temporal and parietal cortices (p < 0.0001) for PET, and for the temporal (p <
      0.005) and parietal (p < 0.001) cortices for SPECT. Temporo-parietal defects were
      detected in all subjects with PET and in 90% with SPECT. CONCLUSION: PET and
      SPECT are able to detect characteristic temporo-parietal abnormalities in
      probable AD. However, the presence of abnormalities in other associative areas is
      better evaluated with PET.

PMID- 8294988
TI  - Technetium-99m-HMPAO SPECT, CT and MRI in the evaluation of patients with chronic
      traumatic brain injury: a correlation with neuropsychological performance.
AB  - The purposes of this study were: (1) to compare 99mTc
      hexamethylpropyleneamineoxime (HMPAO) SPECT with CT and MRI in chronic traumatic
      brain injury (TBI) patients and (2) to correlate both functional and structural
      neuroimaging measurements of brain damage with neuropsychological (NP)
      performance. METHODS: Twenty-nine patients (minor TBI, n = 15 and major TBI, n =
      14) and 17 normal controls (NC) underwent HMPAO SPECT, CT, MRI and NP testing.
      Imaging data were analyzed both visually and quantitatively. RESULTS: Nineteen
      (66%) patients showed 42 abnormalities on SPECT images, whereas 13 (45%) and 10
      (34%) patients showed 29 abnormalities on MRI and 24 abnormalities on CT. SPECT
      detected relatively more abnormalities than CT or MRI in the minor TBI subgroup.
      The TBI group showed impairment on 11 tests for memory, attention and executive
      function. Of these, the anterior-posterior ratio (APR) correlated with six tests,
      whereas the ventricle-to-brain ratio (VBR), a known structural index of a poor NP
      outcome, correlated with only two tests. CONCLUSION: In evaluating chronic TBI
      patients, HMPAO SPECT, as a complement to CT or MRI, may play a useful role by
      demonstrating brain dysfunction in morphologically intact brain regions and
      providing objective evidence for some of the impaired NP performance.

PMID- 8294989
TI  - Evaluating traumatic brain injury: correlating perfusion patterns and function.

PMID- 8294990
TI  - SPECT measurement of benzodiazepine receptors in human brain with iodine-123
      iomazenil: kinetic and equilibrium paradigms.
AB  - Iodine-123-iomazenil binding to benzodiazepine receptors in human brain was
      measured with SPECT using kinetic and equilibrium methods. METHODS: In the
      kinetic experiments (n = 6), regional time-activity curves after a single bolus
      injection of the tracer were fit to a three-compartment model to provide
      estimates of the rate constants K1 to k4. The binding potential (equal to the
      product of the receptor density and affinity) was derived from the rate
      constants. In the equilibrium method (n = 8), the tracer bolus injection was
      followed by a constant tracer infusion to induce a sustained equilibrium state.
      The regional equilibrium volume of distribution was calculated as the ratio of
      the regional brain concentration-to-the free parent tracer steady-state plasma
      concentration. In three experiments, a receptor-saturating dose of flumazenil was
      injected for direct measurement of the nondisplaceable compartment distribution
      volume. RESULTS: The kinetic and equilibrium method results were in good
      agreement in all regions investigated. Iodine-125-iomazenil binding potential
      measured in vitro in 12 postmortem samples was found to be consistent with SPECT
      in vivo measurements. CONCLUSION: These studies demonstrated the feasibility of
      quantification of receptor binding with SPECT.

PMID- 8294991
TI  - A method for assessing the significance of abnormalities in HMPO brain SPECT
      images.
AB  - METHODS: A normal atlas for HMPAO rCBF SPECT images was obtained from images of
      53 normal controls. Following image registration and normalization, a mean image
      was extracted, while images representing correlated normal deviants were
      identified using principal component analysis. These images formed the "building
      blocks" of the atlas. For subsequent images, the atlas was used to create a
      "nearest normal equivalent" image, which was compared to a residual standard
      deviation image to determine the significance of deviations in the new image.
      RESULTS: Images from 30 patients (10 with Alzheimer's disease; 12 with single or
      multiple infarcts; and 8 normals) were analyzed. CONCLUSION: Using an optimal
      decision level, 10/10 patients with Alzheimer's disease and 11/12 patients with
      infarcts were correctly identified, with only one false-positive resulting. We
      utilized a database of images obtained from normal controls to create a normal
      atlas.

PMID- 8294992
TI  - Indium-111-white blood cell scintigraphy in Crohn's patients with fistulae and
      sinus tracts.
AB  - METHOD: Indium-111-white blood cell (111In-WBC) images of 17 Crohn's patients
      with fistulae and sinus tracts were reviewed and correlated with radiographic
      results (n = 16 patients) and surgery (n = 16 patients), to characterize the
      scintigraphic appearance of fistulization and to determine the role of 111In-WBC
      scintigraphy in this clinical setting. These were compared to 50 consecutive
      abnormal 111In-WBC studies obtained in Crohn's patients with suspected active
      disease but no known fistulae or sinus tracts. RESULTS: Scintigraphic findings
      which suggested the presence of fistulae were: (1) the presence of concomitant
      intestinal and extraintestinal lesions and (2) the absence of luminal activity on
      delayed images when early images detected bowel activity. The extraintestinal
      lesions were the drainage site of the fistula (n = 7) or an accompanying abscess
      (n = 6). Absence of luminal activity occurred in seven patients with fistulae and
      in two without fistulae; two patients had a proximal colostomy, two patients had
      bowel obstruction and five patients had fistulae to the skin (n = 3) or between
      the ileum and distal colon (n = 2). The distribution of active bowel disease as
      assessed scintigraphically was in complete agreement with surgery in 14 of 17
      cases (82%) compared to 9 of 15 cases (60%) when correlating radiographic
      assessment with surgery. All surgically proven abscesses were detected on 111In
      WBC images. CONCLUSION: These results indicate that 111In-WBC scintigraphy adds
      useful information to radiographic studies that is essential for appropriate
      management of Crohn's patients with fistulae and sinus tracts.

PMID- 8294993
TI  - Captopril renal scintigraphy in patients with hypertension and chronic renal
      failure.
AB  - The aim of this prospective study was to determine the ability of the captopril
      renogram to reveal the presence of angiotensin II-dependent renovascular disorder
      in hypertensive patients with chronic renal failure and to assess the possibility
      of predicting beneficial effect of angiotensin-converting enzyme (ACE) inhibitors
      on renal function. METHODS: Forty-one patients were evaluated. Baseline renal
      scintigraphy was performed with 80 MBq of 99mTc-mercaptoacetyltriglycine (MAG3)
      injected intravenously. Scintigraphy was repeated within a week with 25 mg of
      oral captopril given 60 min prior to the test. Using the measurements outlined by
      the Working Party on Diagnostic Criteria of Renovascular Hypertension with
      Captopril Renography, the patients were categorized into high (7 patients),
      indeterminate (19 patients) and low (15 patients) probability for renal artery
      stenosis (RAS). RESULTS: In five of the seven patients with high probability, the
      presence of RAS was confirmed angiographically and corrective surgical procedure
      performed in two. In patients with GFR of 10 ml/min/1.73 m2 and/or split renal
      function of 10% or less, all qualitative and semiquantitative scintigraphic
      parameters were nonspecific. Mean parenchymal transit time of tracer was a useful
      parameter to predict the beneficial effect of ACE inhibition therapy in 23
      patients (14 low and 9 indeterminate probability of RAS). CONCLUSION: In
      hypertensive patients with renal failure, captopril renal scintigraphy can be
      utilized to identify the presence of angiotensin II-dependent renal dysfunction
      and possibly help to predict the beneficial effect of ACE inhibitor therapy.

PMID- 8294994
TI  - Should the role of captopril renography extend to the evaluation of chronic renal
      disease?

PMID- 8294995
TI  - Serum thyroglobulin and iodine-131 whole-body scan in the diagnosis and
      assessment of treatment for metastatic differentiated thyroid carcinoma.
AB  - Because of the limitations of periodic 131I whole-body scans, including
      suspension of substitution therapy, questionable sensitivity and low yield in
      detecting metastases in patients who have undergone thyroidectomy, serum
      thyroglobulin and 131I whole-body scans were evaluated for sensitivity in
      detecting local, regional or distant metastases in 261 patients with
      differentiated thyroid carcinoma after total thyroidectomy and ablation. METHODS:
      A noncompetitive immunoradiometric assay was used for serum thyroglobulin
      determination. An 131I whole-body scan was obtained after replacement therapy had
      been suspended for 6 wk or when TSH reached levels higher than 50 microU/ml. In
      patients who underwent radiological procedures with iodinated contrast media, the
      waiting period before the 131I whole-body scan was no less than 10 wk. RESULTS:
      Of the 58 patients with proven metastases who were followed for 12 yr (mean 7 +/-
      3.3 yr), 51 (88.4%) had high serum thyroglobulin assays performed while under
      full replacement therapy and 32 (55%) showed clear 131I whole-body scan
      localization. There were no instances of positive whole-body scans and negative
      serum thyroglobulin. CONCLUSION: In patients treated with 131I, serum
      thyroglobulin assay was an excellent method to assess treatment. Patients with
      metastatic disease and negative whole-body scans with or without serum
      thyroglobulin exhibited a trend toward higher mortality. This trend may also
      indicate that the lack of 131I trapping and low thyroglobulin is a sign of
      metabolic dedifferentiation of otherwise histologically differentiated thyroid
      tumors.

PMID- 8294996
TI  - Diagnostic evaluation of thyroid involvement by histiocytosis X.
AB  - We report the successful diagnosis of thyroid involvement by histiocytosis X due
      to accurate evaluation of nuclear medicine results. METHODS: A total
      thyroidectomy specimen from our patient was initially suggestive of medullary
      thyroid carcinoma. However, histologic reevaluation was performed on the basis of
      nuclear medicine findings which were incompatible with the original histologic
      diagnosis. RESULTS: Immunohistochemical and light microscopy studies were
      performed to obtain the correct diagnosis. Diffuse thyroid involvement by
      histiocytosis X was demonstrated. CONCLUSION: Thyroid scintigraphy was helpful in
      successfully diagnosing thyroid involvement by histiocytosis X. Because tracer
      uptake is related to increased cellularity and metabolism, none of these tracers
      reported here is specific for defining histiocytosis X.

PMID- 8294997
TI  - Pulmonary uptake in indium-111-antimyosin Fab fragment imaging following human
      cardiac transplantation.
AB  - Recent studies suggest that cardiac uptake of 111In-labeled antimyosin monoclonal
      antibody may be estimated semiquantitatively by calculating a heart-to-lung
      activity ratio, with pulmonary uptake serving as a reference region. METHODS: We
      obtained 96 111In-antimyosin scintigraphs to monitor rejection occurrence after
      heart transplantation in 26 patients. RESULTS: On five scintigraphs, the count
      rate density in ROIs over the lungs was markedly higher (mean 53% higher) than
      that in the immediately preceding and following scintigraphs, whereas the
      activity in the heart was essentially unchanged. Four of these scintigraphs
      coincided with ongoing pulmonary infection and the fifth with an occurrence of a
      high anti-CMV titer. CONCLUSION: The mechanism of apparent nonspecific antimyosin
      accumulation in the lungs is uncertain, although increased capillary permeability
      may be one possibility. Attention should be given to activity in the lungs if
      this activity is used as a reference in studies of 111In-antimyosin uptake in the
      heart.

PMID- 8294998
TI  - Antisense DNA delivery in vivo: liver targeting by receptor-mediated uptake.
AB  - Antisense oligodeoxynucleotides coupled to asialoglycoprotein carrier molecules
      were evaluated in terms of their ability to accumulate preferentially in the
      liver and thus potentially serve as an important method to regulate liver gene
      expression. METHODS: Native and asialo-human alpha-1 acid glycoproteins were
      derivatized with low molecular weight poly(L)lysine and complexed with an
      antisense DNA (67 mer) complementary to the 5' end of rat serum albumin mRNA. The
      asialoglycoprotein antisense complex (conjugate) was characterized with respect
      to size, stability, and anti-sense loading, and the biodistribution of the
      conjugate was determined for normal rats at 5 min and 1, 6, and 24 hr after
      intravenous injection. In vivo stability of the anti-sense asialoglycoprotein
      complex was also evaluated using double-labeled (32P-antisense and 3H
      glycoprotein) preparations. RESULTS: The results of the conjugate
      characterization studies demonstrated that at least 30% of the anti-sense DNA
      dissociated from the carrier after 7 min under chromatographic conditions. When
      the conjugate was incubated with PBS, MEM or MEM plus 10% FBS for 1 hr at 37
      degrees C, about 85% of the antisense DNA was dissociated from the carrier. The
      results of the biodistribution studies showed that the accumulation of the asialo
      glycoprotein anti-sense complex in the liver was rapid and greatly exceeded the
      accumulation of the sialo-glycoprotein antisense analog or antisense alone.
      CONCLUSION: These findings have significant implications for the targeted
      delivery of therapeutic antisense molecules to the liver.

PMID- 8294999
TI  - Imaging vascular endothelial activation.

PMID- 8295000
TI  - Thrombus imaging with technetium-99m synthetic peptides based upon the binding
      domain of a monoclonal antibody to activated platelets.
AB  - Monoclonal antibodies which recognize fibrin or platelets have enabled imaging of
      vascular thrombi, however, early imaging has been difficult because of the slow
      blood disappearance of even small antibody fragments. It was theorized that it
      might be possible to synthesize peptides which possess the same thrombus affinity
      as monoclonal antibodies, but which would leave the blood pool much more rapidly.
      METHODS: In this study, peptides were synthesized with amino acid sequences based
      on the primary binding region of the platelet glycoprotein IIb/IIIa-directed
      monoclonal antibody PAC1. Both termini of the peptides were blocked to prevent
      rapid proteolysis and a metallothionein-derived sequence was incorporated as a
      chelating agent for reduced technetium. RESULTS: Technetium-99m-labeled peptides
      produced images of fresh clots in the jugular veins of rabbits and day-old
      thrombi in the femoral veins of dogs within 2 hr after injection. In control
      experiments, a 99mTc-labeled nonspecific peptide failed to produce focal images
      of thrombus. Another control compound, 99mTc-glucoheptonate, did produce images
      of fresh clots in rabbits but failed to produce focal images of day-old thrombi.
      As was hoped, blood clearance of the 99mTc peptides was rapid, with excretion
      through the kidneys, however, none of the peptides studied had better thrombus-to
      blood ratios than iodinated fibrinogen and all had significantly lower deposition
      in the thrombus. CONCLUSION: Using labeled synthetic peptides appears to be
      technically feasible but the absolute binding to thrombus is not yet sufficient
      for reliable imaging of pre-existing thrombi.

PMID- 8295001
TI  - Accumulation enhancement of human monoclonal antibody HB4C5 to lung tumor
      xenografts by N-deglycosylation.
AB  - The fractional uptake of intact monoclonal antibodies by tumors is relatively
      low. Various methods to alter the molecular structure have been used to augment
      tumor uptake. These chemical manipulations, however, may alter the specificity of
      antibody binding. METHODS: Comparative studies of biodistribution,
      radioimmunoimaging and macroautoradiography in LC-6 xenografted mice were
      conducted with the 125I-labeled intact and N-terminal deglycosylated monoclonal
      antibodies to evaluate the effect on deglycosylation on antibody binding.
      RESULTS: The removal of N-glycosyl residues from this monoclonal antibody
      significantly enhanced specific localization of the radioactivity to the tumor,
      especially to its necrotic fraction. Nonspecific accumulation of radioactivity to
      the necrotic fraction of the tumor was excluded by biodistribution studies
      demonstrating selective accumulation of 125I-labeled monoclonal antibody after
      coadministration of 125I-monoclonal antibody (intact or N-deglycosylated) with
      131I-labeled control IgM. CONCLUSION: The lung cancer-associated human monoclonal
      antibody HB4C5, which recognizes histone H2B as the antigen, accumulates
      specifically to the necrotic fraction of tumor. The uptake is enhanced by removal
      of N-terminal glycosyl residues from the antigen-binding site of the light chain.

PMID- 8295002
TI  - Treatment of small-cell lung cancer xenografts with iodine-131-anti-neural cell
      adhesion molecule monoclonal antibody and evaluation of absorbed dose in tissue.
AB  - Human small-cell lung cancer (SCLC) is considered a feasible target for
      immunotherapy using a radiolabeled monoclonal antibody (Mab). A murine Mab, NE150
      (IgG1), reacts with the neural cell adhesion molecule, which is identical to
      cluster 1 antigen of SCLC. METHODS: To estimate their therapeutic effects, NE150
      and an isotype-matched control Mab were labeled with 131I and administered
      intravenously as a single dose into athymic mice inoculated with a NCI-H69 SCLC
      xenograft. The absorbed dose in organs was also examined based upon a long-term
      biodistribution study of 131I-NE150. RESULTS: Tumors (initial volume 563.4 +/-
      223.5 mm3) treated with 11.1 MBq (300 microCi) of 131I-NE150 diminished and
      became invisible at days 30-33, demonstrating a 60-day mean growth delay to reach
      a tripled initial volume compared with sham-treated tumors. Cumulative absorbed
      doses were estimated to be 2310, 410, 500, 330, and 790 cGy for the tumor, liver,
      kidney, spleen and lung, respectively. CONCLUSION: Iodine-131-NE150 had potent
      therapeutic effects against SCLC transplants in athymic mice, however, careful
      assessment of the side effects, improvement of radioiodination and chimerization
      of the Mab might be necessary to achieve efficient targeting in clinical
      therapeutic applications.

PMID- 8295003
TI  - The importance of accurate radiation dosimetry in radioimmunotherapy of cancer.

PMID- 8295004
TI  - Cellular dosimetry: absorbed fractions for monoenergetic electron and alpha
      particle sources and S-values for radionuclides uniformly distributed in
      different cell compartments.
AB  - The importance of cellular dosimetry in both diagnostic and therapeutic nuclear
      medicine is becoming increasingly recognized. METHODS: Experimental range-energy
      relations for electrons and alpha particles, along with derived geometric
      reduction factors, are used to calculate cellular absorbed fractions for these
      radiations. The resulting absorbed fractions are employed to calculate cellular S
      values for several radionuclides. RESULTS: Cellular absorbed fractions for
      monoenergetic electron sources with energies ranging from 0.1 keV to 1 MeV,
      distributed uniformly in the source region, are calculated for several target<-
      source combinations including cell<--cell, cell<--cell surface, nucleus<-
      nucleus, nucleus<--cytoplasm and nucleus<--cell surface. Similar data are also
      provided for monoenergetic alpha particle sources with energies ranging from 3 to
      10 MeV. S-values are also conveniently tabulated for 32P, 35S, 86Rb, 89Sr, 90Y,
      91Y, 114mIn, 131I. Auger-electron-emitters 51Cr, 67Ga, 99mTc, 111In, 123I, 125I,
      201TI, 203Pb and the alpha emitter 210Po. In addition, S-values are given for
      radionuclides in the 212Pb decay series, including 212Pb, 212Bi and 212Po. Both
      absorbed fractions and S-values are supplied for a number of different size cells
      and cell nuclei. CONCLUSIONS: With the absorbed fractions and S-values in hand,
      along with experimentally determined information on the biokinetics and
      subcellular distribution of the radionuclides, the cellular self-absorbed dose
      can be conveniently calculated.

PMID- 8295005
TI  - Gallium-67/gallium-68-[DFO]-octreotide--a potential radiopharmaceutical for PET
      imaging of somatostatin receptor-positive tumors: synthesis and radiolabeling in
      vitro and preliminary in vivo studies.
AB  - When labeled with gamma-emitting radionuclides, somatostatin analogs have the
      potential to localize somatostatin receptor-positive tumors using gamma camera
      scintigraphy. We present a somatostatin analog, [DFO]-octreotide (SDZ 216-927),
      that comprises desferrioxamine B coupled to octreotide via a succinyl linker.
      This conjugate can be labeled with either 67Ga for gamma scintigraphy or 68Ga for
      PET imaging. The 67Ga-labeled conjugate is stable in vitro to autoradiolysis over
      a 24-hr period. METHODS: Rats bearing a somatostatin receptor-positive pancreatic
      islet cell tumor were injected with 20 MBq of 67Ga[DFO]-octreotide (33 GBq
      67Ga/mumole). RESULTS: After 1 hr, the accumulation of 67Ga[DFO]-octreotide was
      0.38 +/- 0.08 %ID/g and the tumor-to-nontumor ratios for blood, muscle, liver and
      intestine were 2.5, 7.4, 1.9 and 1.6, respectively. PET studies with 68Ga[DFO]
      octreotide recorded a very rapid accumulation at the tumor and a subsequent
      residence half-life of about 6 hr. CONCLUSION: Gallium-68-[DFO]-octreotide can be
      used in PET studies to diagnose receptor-positive tumors such as
      gastroenteropancreatic, small-cell lung and breast tumors.

PMID- 8295006
TI  - Discriminated release of a hippurate-like radiometal chelate in nontarget tissues
      for target-selective radioactivity localization using pH-dependent dissociation
      of reduced antibody.
AB  - To achieve high and selective target radioactivity localization by monoclonal
      antibodies (Mabs) labeled with metallic radionuclides, the discriminated release
      of a hippurate-like radiometal chelate in nontarget tissues was performed using
      chemically modified Mabs. METHODS: The disulfide bonds of a Mab against
      osteogenic sarcoma (OST7, IgG1) were reduced and 67Ga chelate of
      succinyldeferoxamine (SDF) was conjugated proximal to the Mab molecule via an
      ester bond with exposed thiol groups (67Ga-DFO-MESS-redOST7), which would impair
      esterase access to the ester bond of 67Ga-DFO-MESS-redOST7 due to the steric
      interference induced by bulky antibody molecule, stabilizing the ester bond in
      plasma and on the target cell's surface. Gallium-67-SDF was also conjugated to
      OST7 via an ester bond with 2-iminothiolane to render the ester bond in a
      position distal from the OST7 molecule (67Ga-DFO-MESS-IT-OST7). RESULTS: Although
      SDS-PAGE analyses of 67Ga-DFO-MESS-redOST7 showed a partial cleavage of its
      disulfide bonds, size-exclusion HPLC and cell binding assays indicated that the
      IgG structure and immunoreactivity of this conjugate were preserved in a neutral
      buffer and plasma of the systemic circulation. CONCLUSION: The present
      radiochemical design of an antibody utilizing pH-dependent dissociation would
      constitute a promising approach in establishing selective target radioactivity
      localization by Mabs.

PMID- 8295007
TI  - Bis(dithiocarbamato) nitrido technetium-99m radiopharmaceuticals: a class of
      neutral myocardial imaging agents.
AB  - The synthesis and biodistribution in various animal models (rat, dog, pig and
      monkey) of 99mTc radiopharmaceuticals containing the Tc = N multiple bond are
      reported. METHODS: The complexes are represented by the general formula
      99mTcN(L)2, where L is the monoanionic form of a dithiocarbamate ligand of the
      type [R1(R2)-N-C(=S)S]-, and R1 and R2 are variable, lateral groups. The
      preparations were carried out, both as a liquid and freeze-dried formulation,
      through a simple procedure involving the initial reaction of [99mTcO4]- with S
      methyl N-methyl dithiocarbazate [H2NN(CH3)C(=S)SCH3], in the presence of tertiary
      phosphines or Sn2+ ion as reductants, followed by the addition of the sodium salt
      of the ligand (NaL) to afford the final product. The chemical identity of the
      resulting complexes was determined by comparing their chromatographic properties
      with those of the corresponding 99Tc analogs characterized by spectroscopic and x
      ray crystallographic methods. The complexes are neutral and possess a distorted,
      square pyramidal geometry. RESULTS: No decomposition of the complexes, in
      physiological solution, was observed over a period of 6 hr. Imaging and
      biodistribution studies demonstrated that these radiopharmaceuticals localize
      selectively in the myocardium of rats, dogs and primates, but that they failed to
      visualize the pig heart. The kinetics of heart uptake and clearance were studied
      in rats and dogs, and found to be strongly influenced by variation of the lateral
      R1 and R2 groups. CONCLUSION: The high quality of myocardial images obtained in
      dogs and monkeys demonstrates that the derivative 99mTcN[E-t(EtO)NCS2]2
      [99mTcN(NOEt)] exhibits the most favorable distribution properties for further
      studies in humans.

PMID- 8295008
TI  - Pinhole SPECT: an approach to in vivo high resolution SPECT imaging in small
      laboratory animals.
AB  - The performance of pinhole SPECT and the application of this technology to
      investigate the localization properties of radiopharmaceuticals in vivo in small
      laboratory animals are presented. METHODS: System sensitivity and spatial
      resolution measurements of a rotating scintillation camera system are made for a
      low-energy pinhole collimator equipped with 1.0-, 2.0- and 3.3-mm aperture
      pinhole inserts. The spatial detail offered by pinhole SPECT for in vivo imaging
      was investigated in studies of the brain and heart in Fisher 344 rats by
      administering 201TICI, 99mTc-HMPAO, 99mTc-DTPA and 99mTc-MIBI. Image acquisition
      is performed using a rotating scintillation camera equipped with a pinhole
      collimator; projection data are acquired in conventional step-and-shoot mode as
      the camera is rotated 360 degrees around the subject. Pinhole SPECT images are
      reconstructed using a modified cone-beam algorithm developed from a two
      dimensional fanbeam filtered backprojection algorithm. RESULTS: The reconstructed
      transaxial resolution of 2.8 mm FWHM and system sensitivity of 0.086 c/s/kBq with
      the 2.0-mm pinhole collimator aperture provide excellent spatial detail and
      adequate sensitivity for imaging the regional uptake of the radiopharmaceuticals
      in tumor, organs and other tissues in small laboratory animals. CONCLUSION: The
      resolution properties of pinhole SPECT are superior to those which have been
      achieved thus far with conventional SPECT or PET imaging technologies. Pinhole
      SPECT provides an important approach for investigating localization properties of
      radiopharmaceuticals in vivo.

PMID- 8295009
TI  - Evaluation of the hepatobiliary excretion of technetium-99m-MAG3 and
      reconstitution factors affecting radiochemical purity.
AB  - Technetium-99-MAG3 is a renal tubular function agent. However, sporadic liver and
      gallbladder visualization have raised questions about kit stability, impurities
      and nonrenal routes of excretion. To address these issues, studies were conducted
      to optimize the labeling efficiency of the TechneScan MAG3 kit and to evaluate
      the hepatobiliary excretion of the MAG3 complex. METHODS: Thirty-six vials of the
      commercial formulation of 99mTc-MAG3 were prepared according to manufacturer's
      instructions and evaluated for radiochemical purity using two methods: a
      combination of high-performance liquid chromatography and paper chromatography
      (HPLC/PC); and the manufacturer's miniature chromatography system (Sep-Pak
      procedure). RESULTS: The labeling efficiency was significantly higher when the
      kit was reconstituted with 10 ml (96.6%) of saline versus 5 ml (91.4%) (p <
      0.01). The radiochemical purity of the kits remained stable for up to 6 hr, but
      the purity determined by Sep-Pak averaged 2.5% higher than that determined by
      HPLC procedures (p < 0.01). Rat studies to evaluate renal and hepatobiliary
      elimination of MAG3 showed no difference in the %ID excreted into the urine by 60
      min in all groups of animals studied. However, the %ID excreted into the bile was
      significantly higher for the kit formulation than the HPLC-purified MAG3, 9.9%
      versus 6.6% (p = 0.0475). CONCLUSION: The radiochemical purity of the TechneScan
      MAG3 kit can be improved by reconstituting with larger volumes. In addition, the
      studies in rats suggest that fasting or kit impurities may be a contributing
      factor to increased hepatobiliary visualization in patient studies.

PMID- 8295010
TI  - A quantitative phantom analysis of artifacts due to hepatic activity in
      technetium-99m myocardial perfusion SPECT studies.
AB  - We have observed that filtered backprojection may cause artifactual decreased
      myocardial wall uptake in the reconstructed images if the hepatic-to-cardiac
      activity ratio (HCR) in 99mTc clinical myocardial SPECT studies is sufficiently
      high (> 1). METHODS: To quantitatively relate hepatic uptake to this phenomenon,
      a commercial chest and heart phantom was modified with the addition of a
      customized liver insert, which was filled with various concentrations of 99mTc to
      simulate HCRs of 0:1, 1:1 and 2:1. The phantom was imaged with a high
      sensitivity, three-detector camera, low-energy, high-resolution (LEHR)
      collimation and 180 degrees noncircular orbits. RESULTS: Quantitative
      circumferential profile analysis of the reoriented SPECT images demonstrated
      artifactual inferior/inferoseptal maximal activity decreases of 17.8% and 46.2%
      for the 1:1 and 2:1 HCRs, compared to the 0:1 HCR. Hepatic scatter probably
      partly mitigates the decrease. Smoothing the projection data before
      reconstruction worsened the artifacts' severity. Using Butterworth filters of
      order 5 and cutoff frequencies of 0.1, 0.2 and 0.215 Nyquist (clinical standard)
      resulted in artifactual inferior wall activity decreases of 5%, 8% and 16%,
      compared to using the same filter with a cutoff of 0.3 for an HCR of 2:1.
      CONCLUSION: These data indicate that if count statistics are good and liver
      uptake is high, higher frequency cutoffs in pre-reconstruction filters may
      improve specificity in 99mTc-labeled myocardial perfusion SPECT studies.

PMID- 8295011
TI  - A transmission-dependent method for scatter correction in SPECT.
AB  - A method of scatter compensation has been developed that incorporates planar
      transmission measurements in the estimation of photopeak scatter in SPECT.
      METHODS: The scatter distribution is first estimated by convolving the planar
      projections with a monoexponential scatter function. The number of scattered
      events that subsequently reach the detector as a proportion of total events
      (i.e., scatter fraction) is then determined for each point in the projections
      based on narrow-beam transmission values, obtained using an external source. The
      assumptions of the method were tested using 99mTc and 201Tl point and line
      sources. The quantitative and qualitative impact of transmission-dependent
      scatter correction was assessed in realistic phantom experiments simulating blood
      pool, lung and myocardial perfusion studies. RESULTS: The method accurately
      predicts the scatter distribution from 99mTc and 201Tl line sources in a phantom
      with variable density. Reconstructed counts are artificially enhanced in regions
      of high tissue density when scattered events are not removed from the projections
      prior to attenuation correction. Using convolution-subtraction with a constant
      scatter fraction (k = 0.4), scatter is underestimated in the heart and
      overestimated in the lungs, whereas transmission-dependent scatter correction
      enables activity to be quantified with > or = 95% accuracy in heart and lung
      regions. CONCLUSION: We conclude that incorporating transmission data enables
      accurate scatter compensation in objects with nonuniform density.

PMID- 8295012
TI  - Radon update: facts concerning environmental radon: levels, mitigation
      strategies, dosimetry, effects and guidelines. SNM Committee on Radiobiological
      Effects of Ionizing Radiation.
AB  - The risk from environmental radon levels is not higher now than in the past, when
      residential exposures were not considered to be a significant health hazard. The
      majority of the radon dose is not from radon itself, but from short-lived alpha
      emitting radon daughters, most notably 218Po(T1/2 3 min) and 214Po (T1/2 0.164
      msec) along with beta particles from 214Bi (T1/2 19.7 min). Radon gas can
      penetrate homes from many sources and in various fashions. Measuring radon in
      homes is simple and relatively inexpensive and may be accomplished in a variety
      of ways. Although it is not possible to radon-proof a house, it is possible to
      reduce the level. In high radon areas, if the average level is higher than 4-8
      pCi/liter (NCRP recommended level is 8 pCi/liter; EPA recommended level is 4
      pCi/liter), appropriate action is advised. The shape of the dose response curves
      for miners exposed to alpha-emitting particles in the workplace is consistent
      with current biologic knowledge. It is linear in the low dose range and saturates
      in the high dose range. No detectable increase in lung cancer frequency is seen
      in the lowest exposed miners (those with exposures < 120 WLM, the relevant dose
      interval for most homes). Evidence for a health effect from radon exposure is
      based on data from animal studies and epidemiologic studies of mines. Extensive
      radiobiologic data predict a linear dose-response curve in the low dose region
      due to poor biological repair mechanisms for the high density of ionizing events
      that alpha particles create. However, no compelling evidence for increased cancer
      risks has yet been demonstrated from "acceptable" levels (< 4-8 pCi/liter).

PMID- 8295013
TI  - Professionalism and nurse-midwifery.

PMID- 8295014
TI  - Fundal height measurement. Part 4--Accuracy of clinicians' identification of the
      uterine fundus during pregnancy.
AB  - The purpose of this study was to determine how accurately clinicians can identify
      the uppermost border of the uterine fundus when they obtain fundal height
      measurements. Clinicians were instructed to identify the uppermost border of the
      uterine fundus in their usual manner and make a small pen mark on the maternal
      abdomen at that point. Real-time ultrasonography was then used to locate the
      actual level of the fundus and measure the distance between the clinician's
      assessment and the actual level of the fundus. Measurements were obtained from
      126 women. Six clinicians participated in the study, and the differences between
      the clinicians' errors were not statistically significant (F = 1.26; d.f. =
      5,120; P = .2873). For the entire series, the mean error was -.45 cm (SD = 1.99
      cm), the mean absolute error was 1.25 cm, the maximal error was 8.6 cm, the
      percentage of errors that exceeded 1 cm was 42.1%, and the percentage of errors
      that exceeded 2 cm was 20.6%. Examiner error was not associated with factors such
      as maternal height, prepregnancy weight, present weight, prepregnancy body mass
      index, parity, gestational weeks, the amount of fat on the anterior abdominal
      wall, or the presence of the placenta or fetal parts in the fundus. Examiner
      error was influenced by thickness of the uterine wall and fetal presentation.
      These findings indicate that clinicians make errors in identifying the uterine
      fundus in a significant number of cases and that the methods used by clinicians
      to identify the uterine fundus need to be evaluated and improved.

PMID- 8295015
TI  - Preterm birth prevention programs. A critique of current literature.
AB  - Published reports of the effectiveness of preterm birth prevention programs have
      produced mixed results. Many larger observational studies suggest benefit. The
      randomized trials, however, suggest no effect on reducing rates of preterm birth
      in high-risk populations. This article reviews and critiques these reports and
      suggests areas for further research.

PMID- 8295016
TI  - Water immersion and the effect on labor.
AB  - The use of warm water immersion (WI) by women for relaxation during labor is
      being used around the world; however, there is little available research as to
      the effects of WI. We conducted this prospective, randomized, and controlled
      study to determine the safety and effect of WI on the woman in labor. We studied
      93 subjects between 36 and 41 weeks' gestation, in active labor, with intact
      membranes, and without major medical or obstetric complications. Subjects in the
      WI group utilized a tub in labor along with other pain relief measures such as
      ambulation, rest, showers, and analgesics. Subjects in the no-WI group could use
      all available methods of pain relief except WI. Water immersion did not alter the
      rate of cervical dilation, change the contraction pattern, change the length of
      labor, or alter the use of analgesia. The rates of chorioamnionitis and
      endometritis were not altered by WI. Although we did not demonstrate an
      improvement in progression of labor by WI, there was no evidence of increased
      maternal, neonatal, or infectious morbidity.

PMID- 8295017
TI  - Research trends in the Journal of Nurse-Midwifery 1987-1992.
AB  - To identify selected research trends, 69 research reports were analyzed from a
      sample of feature articles that were published in the Journal of Nurse-Midwifery
      between 1987 and 1992. Systematic appraisal was performed to classify these
      articles according to topic, design, sampling methodology, sample size, and
      funding. The largest proportion of studies were conducted on clinical topics
      (83%). Descriptive study designs were utilized most frequently (67%).
      Nonprobability sampling (81%) far exceeded probability sampling (19%); however,
      in 1992, probability sampling increased to 75%. With the exception of 1988,
      funding steadily increased over the study period. These results suggest that
      research has primarily focused upon clinical issues and has utilized descriptive
      designs and nonprobability sampling.

PMID- 8295018
TI  - Nurse-midwives as faculty preceptors in medical student education.
AB  - Certified nurse-midwives (CNMs) are specialists in normal obstetrics and women's
      health care. In this capacity, CNMs have been actively involved in the education
      of nurses and student nurse-midwives. Nurse-midwives also have been consultants
      and mentors for medical students and residents during their clinical experiences.
      However, the nurse-midwife's contribution to the formal medical education process
      has not received the appropriate formal recognition that it deserves, nor has
      this contribution been utilized to its maximum potential. This article describes
      the development, philosophy, and implementation of an educational program
      utilizing nurse-midwives as the primary clinical preceptor for the obstetric
      rotation for third-year medical students. The long-range impact of this
      educational experience on the nurse-midwife/physician relationship is also
      explored.

PMID- 8295019
TI  - An analysis of the reasons for Japan's low infant mortality rate.
AB  - Japan's infant mortality rate in 1991 was four per 1,000, the lowest in the
      world. Contributing factors are the universal use of the Boshi Kenko Techo
      (maternal-child health handbook) and universal access to care. Most births occur
      to women aged 25-29 years and there are few unmarried mothers. Ninety-nine and
      seven-tenths percent of births are attended by qualified professionals either in
      hospitals or private clinics, with an average stay of one week postpartum.
      Abortion is available when contraceptives fail. There are government subsidies
      for medical, obstetric, and pediatric complications. Japanese citizens are highly
      literate and seek out medical advice, and their society is organized to support
      children. Efficient systems of community support, public health education, and
      excellent medical care encompass events from conception to school age.

PMID- 8295020
TI  - Community-based nurse-midwifery education program. Distance learning in nurse
      midwifery education.
AB  - Distance-learning has greatly expanded the number of students admitted to a nurse
      midwifery education program. This article describes the Community-Based Nurse
      Midwifery Education Program (CNEP) of the Frontier School of Midwifery and Family
      Nursing. The organizational structure and curriculum of the CNEP combines
      apprenticeship learning with academic rigor, permitting students who cannot
      relocate to the university to pursue graduate education. New technology, such as
      an interactive electronic bulletin board, networks students and faculty. The
      program emphasizes theories of independent, adult learning. There is a master's
      completion option available through the affiliation with Case Western Reserve
      University.

PMID- 8295021
TI  - Mandatory advanced degrees for CNMs. Developing compromise.
AB  - Higher education is seen as a step in the right direction for credentialing
      health care provides. The difficulty lies in the continuation of nurse-midwifery
      certificate programs to increase the number of practicing certified nurse
      midwives while maintaining high-quality care. The author offers some pragmatic
      solutions to this dilemma.

PMID- 8295022
TI  - Are we losing the art of midwifery.

PMID- 8295023
TI  - Circumcision: refining a traditional surgical technique.

PMID- 8295024
TI  - Circumcision: refining a traditional surgical technique.

PMID- 8295025
TI  - Nurse-midwifery as it reinforces and transforms the American ideology of gendered
      roles.

PMID- 8295026
TI  - Annual Student Report to the American College of Nurse-Midwives.

PMID- 8295027
TI  - Nurse-midwifery service model in an academic environment.

PMID- 8295028
TI  - Should employees be tested for immunity after hepatitis B vaccination?

PMID- 8295029
TI  - What restrictions regarding work duties or exposures are appropriate when liver
      function abnormalities (especially elevated enzymes) are noted?

PMID- 8295030
TI  - Epidemiologic framework absent.

PMID- 8295031
TI  - Intrinsic causes of keyboard injuries.

PMID- 8295032
TI  - Assessment of the health hazards of 1,3-butadiene and styrene. Meeting report.

PMID- 8295033
TI  - System for quality management.
AB  - Total quality management will provide important benefits for organizations that
      are involved with the delivery of occupational and environmental health care.
      These organizations should shift from traditional medical management to the new
      paradigm. Identification of a set of relevant parameters for this new management
      system is necessary to implement the quality culture within our professional
      settings. An exhaustive literature search was undertaken on the topic of total
      quality management to delineate a framework for consideration by occupational and
      environmental health managers. Proposed are essential components of a management
      system for quality excellence which are derived from review of reported
      approaches among health care organizations and industry, various lists of quality
      principles and criteria, and classical systems theory.

PMID- 8295034
TI  - Quality management in occupational and environmental health programs. Benefit or
      disaster?

PMID- 8295035
TI  - Aplastic anemia and pesticides. An etiologic association?
AB  - The majority of cases of aplastic anemia, a rare previously lethal disease, are
      of unknown etiology. Nevertheless, for the past 3 decades, case reports and case
      series of aplastic anemia have suggested an etiologic association between
      aplastic anemia and pesticide exposure. A review of the medical literature,
      including basic science literature, confirms a possible etiologic association
      between pesticide exposure and aplastic anemia. Two hundred and eighty cases of
      aplastic anemia associated with pesticide exposure were reported in the
      literature. The majority of these cases were young (mean age, 34 years; median,
      28), with a short latency (mean, 5 months) and with a history of occupational
      exposure to pesticides. The pesticide exposures reported were the organochlorines
      and organophosphates, both commonly used pesticides throughout the world.
      Therapeutic and methodologic issues as well as future directions for research
      into this etiologic association are discussed.

PMID- 8295036
TI  - Traumatic fatalities at work. American Indians and Alaska natives, 1980 through
      1988.
AB  - To define the rates and characteristics of fatal occupational injuries among
      American Indians and Alaska Natives (AI/AN) in the United States, we examined
      death certificates included in the National Traumatic Occupational Fatalities
      data base for deaths occurring from 1980 to 1988. Two hundred and seventy-four
      work-related deaths among AI/AN civilians (259 men, 15 women) were identified. In
      1980, the fatality rate among employed AI/AN was 5.5/100,000 workers compared
      with 7.7/100,000 workers for the United States. Ninety percent of the AI/AN
      deaths were from unintentional injury, 6% from homicide, and 3% from suicide. The
      pattern of fatal occupational injuries among AI/AN differs from that for all
      races combined, especially with regard to the larger percent of AI/AN fatalities
      in the agriculture, forestry, and fishing industry and the high proportion of
      water transportation incidents.

PMID- 8295037
TI  - Impact of regular relaxation training and psychosocial working factors on neck
      shoulder tension and absenteeism in hospital cleaners.
AB  - Occupational stress in hospital cleaners (n = 50), and the effect of relaxation
      training (n = 25, age matched, randomized), were studied by recording the
      electrical activity of the upper trapezius muscle at rest and during working
      conditions at the beginning, middle, and end of a 6-month follow-up period. A
      short (15-minute) relaxation program was practiced daily at the workplace to
      provide stress management. The amount of sick leave was counted, and the extent
      of depression and some psychosocial working factors were screened.
      Intercorrelations were found between the neck-shoulder tension, psychosocial
      factors, depression, and the absentee rate. The relaxation training diminished
      tension in the neck-shoulder region efficiently; nevertheless, the decrease in
      absenteeism might have been related mainly to the social support offered by the
      research maneuver itself.

PMID- 8295038
TI  - Effects on health and social well-being of on-call shifts. An epidemiologic in
      the French National Electricity and Gas Supply Company.
AB  - An investigation of the effects on health and social well-being of on-call shift
      work to cover emergencies outside working hours has been carried out by
      Electricite de France-Gaz de France, the French national company that supplies
      gas and electricity. This transversal survey compared a group of workers exposed
      to on-call shift work (n = 145) with a group that was not (n = 195). Each subject
      completed a questionnaire about the demands of his work, state of health,
      psychologic equilibrium using the Langner scale, and the impact of his job on
      social and family life. A "weekly report form," completed for 3 consecutive weeks
      randomly selected using a sampling plan covering the entire year to take into
      account seasonal variations, was subsequently filled in by 115 of the group
      exposed to on-call shift work and 167 of those who were not, to investigate
      events occurring outside working hours and sleep. The findings show that the main
      demands of being on-call were telephone calls, which were five times more
      numerous during the weeks on-call; this was accompanied by a shorter sleeping
      time (a mean of 6.8 hours versus 7.4 hours during a normal week) and more
      frequent tiredness on waking up (25.7% vs 13.2%). No particular disorder was
      found more frequently in the exposed group, but the psychologic equilibrium and
      family and social life of the workers in the on-call shift group were disturbed:
      some variables in the questionnaire and indices calculated from some items
      revealed adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295039
TI  - An anesthesia mask gas-scavenging system.
AB  - The level of N2O contamination in the breathing zone of anesthesiologists was
      measured while they administered inhalation anesthesia by mask to five patients.
      A mask gas-scavenging attachment was used for 30 minutes and then removed while
      anesthesia continued for a further 30 minutes. The levels of N2O with and without
      the scavenging attachment were compared. Using the scavenging attachment, N2O
      contamination was reduced from greater than 150 ppm to less than 5 ppm, a level
      well below the 25 ppm limit recommended by the National Institute for
      Occupational Safety and Health. The scavenging device is a simple and effective
      way to reduce operating room contamination with N2O during delivery of anesthesia
      by mask.

PMID- 8295040
TI  - Effects of work-site health promotion on illness-related absenteeism.
AB  - This study examined the effects of work-site health promotion on employee
      absenteeism. Thirty-two work sites were randomized to programs for weight control
      and smoking cessation or to no treatment for 2 years. The prevalence of self
      reported absences from work was assessed at baseline and follow-up. Results using
      work site as the unit of analysis showed a net reduction in the percent of
      workers reporting a sick day in the last month in treatment versus control work
      sites of 3.7% (P = .04) and 3.4% (P = .06) in cross-sectional and cohort
      analysis, respectively. Further analyses found that the rate of participation in
      smoking (P = .09) but not weight programs (P = .72) was positively associated
      with change in sick day prevalence and that this effect was strongest in baseline
      smokers (P = .002). It is concluded that work-site smoking cessation programs may
      yield important short-term economic benefits by reducing employee absenteeism.

PMID- 8295041
TI  - Frequency of exercise and dropouts in a work-site program. Correlates of 6-month
      activity patterns.
AB  - Exercise professionals have little information concerning expected levels of
      exercise for new participants. This study examined the frequency of exercise of
      949 employees during their first 6 months of membership in a work-site health
      promotion facility, using automated check-in data. Overall, the frequency of
      exercise declined, the proportion of frequent exercisers declined, and the
      proportion of employees who dropped out increased. Men exercised more frequently
      and were less likely to drop out than were women (P < .01). Younger employees
      exercised more frequently than did older employees. Employees in the middle
      salary level exercised more frequently than did employees in the lower or upper
      levels (P < .01). The employee groups that started out with a lower frequency of
      exercise remained at a lower frequency throughout the 6 months. By their 6th
      month, women were 50% more likely to drop out and 50% less likely to exercise
      regularly than were men. These figures provide a basis for comparison with other
      programs to document expected exercise behavior.

PMID- 8295042
TI  - Achieving our goals in health care reform.

PMID- 8295043
TI  - The use of guided tissue regeneration to improve implant osseointegration.
AB  - This prospective clinical study was designed to examine the use of guided tissue
      regeneration for the bony augmentation of alveolar bone around, or in preparation
      for, titanium endosseous implants. Sixty-three expanded polytetrafluorethylene
      membranes were used in 40 patients for various indications relating to implant
      placement. All of the membranes were subsequently removed. Postoperative
      infections were noted in nine membranes (14%), and dehiscence with exposure of
      the membrane to the oral cavity occurred in nine membranes (14%). Forty-five of
      the augmentations (71%) healed uneventfully and the membranes were removed at an
      average of 4.5 months. Sixty-one of the augmentations (96.8%) were found to be
      successful as determined by the clinical success of the implants and the presence
      of bone where there had been an osseous defect. Two cases (3.2%) were
      unsuccessful. Both of these were complicated by infection. The results indicate
      that guided tissue regeneration is a predictable method of augmenting the bone
      around titanium endosseous implants. Although the early complication rate was
      relatively high, the long-term success of the augmentation usually is not
      affected.

PMID- 8295044
TI  - Achieving mandibular continuity with vascular bone flaps: a comparison of primary
      and secondary reconstruction.
AB  - This retrospective study was performed to compare the functional and aesthetic
      results achieved in two distinct groups of patients undergoing composite
      reconstruction of complex head and neck defects using vascularized bone flaps.
      Fourteen consecutive patients undergoing reconstruction over a 30-month period
      (January 1988 through June 1991), nine primary and five secondary, were analyzed.
      The two groups were similar with respect to age, physical status, tumor type and
      stage, exposure to radiation, and previous history of cigarette smoking and
      alcohol consumption. The bone defect was similar between the two groups, but the
      soft tissue deficit was greater in the group of patients reconstructed
      secondarily. Surgery time and blood loss tended to be less in the patients
      reconstructed secondarily, but length of hospitalization was similar. Flap
      survival was 100%, although the complication rate approached 60%. Restoration of
      mandibular continuity and orofacial soft tissue defects with vascularized
      composite free flaps had a favorable impact on function and aesthetics in the
      group of patients reconstructed primarily. In those reconstructed secondarily the
      benefit was primarily cosmetic. Continued emphasis on primary reconstruction of
      the composite defect with composite free tissue transfers is advised.

PMID- 8295045
TI  - Sternoclavicular grafts for temporomandibular joint reconstruction.
AB  - This study evaluated the long-term outcomes of 52 sternoclavicular grafts for
      temporomandibular joint (TMJ) reconstruction in 38 patients. Patients were
      divided into three groups according to preoperative diagnosis and evaluated an
      average of 45 months (range, 10 to 84 months) postsurgery. Group 1 consisted of
      14 patients (24 joints) with previous Proplast/Teflon implants (P/T; Vitek, Inc,
      Houston, TX;); successful reconstruction was achieved in only four patients (29%)
      and seven joints (29%). Group 2 included 10 patients (14 joints) with
      inflammatory TMJ pathology (non-P/T); success occurred in five patients (50%) and
      eight joints (57%). Group 3 consisted of 14 patients (14 joints) with non-P/T and
      noninflammatory TMJ pathology. Success in this group occurred in 13 patients
      (93%) and 13 joints (93%), with only one failure. The results of this study
      support the use of the sternoclavicular graft for TMJ reconstruction in a select
      group of patients and demonstrate a high failure rate in patients with previous
      P/T implants.

PMID- 8295046
TI  - Estimated masticatory forces in patients before orthognathic surgery.
AB  - There has been relatively little study of masticatory forces in dentofacial
      deformity patients before orthognathic surgery. This study used a mathematical
      equation based on electromyographic activity (EMG) during mastication and forces
      obtained during isometric bites to estimate masticatory forces in 55 control
      subjects and 48 patients. Subjects chewed on a constant bolus while EMG
      recordings were made bilaterally from the superficial masseter, anterior
      temporalis, and posterior temporalis muscles. Unilateral isometric bite forces in
      the first molar position and simultaneous EMGs were recorded in these same
      subjects. Superficial masseter muscle activity and isometric bite forces were
      strongly correlated. The slope of masseter EMG versus isometric force was used to
      estimate the masticatory forces. Males were found to have significantly higher
      estimated masticatory forces than females.

PMID- 8295047
TI  - Severe osteoarthrosis after fracture of the mandibular condyle: a clinical and
      histologic study of seven patients.
AB  - The factors that induce complications subsequent to fractures of the mandibular
      condyle have long been controversial. A clinical and histologic study of seven
      patients (nine temporomandibular joints [TMJs]) who suffered from severe TMJ
      problems subsequent to condylar fractures showed that the complications were
      related to comminution of the condyle, sagittal fracture of the condyle, and
      subcondylar fracture dislocation. Alterations in these TMJs all involved
      secondary osteoarthrosis. Additionally, aseptic necrosis, bifid deformity of the
      condyle (two of the three sagittally fractured condyles), and TMJ ankylosis
      occurred in these patients. It is suggested that the involved fracture patterns
      be given more attention by clinicians.

PMID- 8295048
TI  - The temporalis muscle flap: an evaluation and review of 38 cases.
AB  - This article analyzes the authors' experience with the temporal myofascial flap
      in orbital, maxillary, floor of the mouth, tongue, retromolar trigone, and buccal
      mucosa reconstruction after oncologic surgery. Thirty-eight patients were treated
      and evaluated after using this technique. Four of the patients received the flap
      to restore orbital defects; the other 34 flaps were used in oral reconstruction.
      The flap remained viable in all instances. Most of the patients experienced no
      perioperative complications. Ten patients (29.4%) with flaps transposed to the
      oral cavity showed partial wound dehiscence. Two patients experienced
      temporomandibular joint dysfunction, two severe reduction in the oral aperture,
      22 had mild depression of the temporal fossa, and four had mild to severe
      alteration in the facial aesthetics secondary to bone resection. All flaps
      transposed to the oral cavity showed good epithelialization and adaptation to the
      recipient site.

PMID- 8295049
TI  - Risk factors for the postoperative local recurrence of tongue carcinoma.
AB  - Clinical and histologic studies on the risk factors for the postoperative local
      recurrence of tongue carcinoma were analyzed in 51 patients. Postoperative local
      recurrence occurred in 12 (23.5%), with almost all developing within the first 12
      months after surgery. A comparison of patients with and without recurrence
      indicated that the risk factors for recurrence were 1) endophytic tumor growth,
      2) grade 4 pattern of histologic invasion, and 3) tumor within 5 mm of the
      surgical margin (especially the deep margin). All T1 tumors were less than 5 mm
      deep, indicating that it is reasonable for partial glossectomy to be performed in
      patients with T1 carcinoma. However, for T2 through T4 carcinoma it seems that
      more extensive surgery should be performed because of the variability in depth of
      tumor invasion. The 5-year survival rate of the patients with recurrence was 45%
      and that of patients without recurrence was 73.7% (P < .01). The overall
      prognosis of tongue carcinoma should improve when surgeons take a more prudent
      attitude to the treatment of patients with these risk factors.

PMID- 8295050
TI  - Patient-controlled analgesia: a comparison of dosing regimens for acute
      postsurgical pain.
AB  - This study compares several dosing regimens for patient-controlled analgesia
      (PCA) in the management of acute maxillofacial surgical pain. The dosing methods
      differed by presence or absence of an active drug (morphine [MS] vs saline),
      presence of a baseline infusion, and dose of drug delivered. Sixty-eight patients
      were enrolled in this prospective, randomized, double-blind, placebo-controlled
      trial that lasted 24 hours. The study was completed in two separate parts, each
      of which involved randomization of patients into four groups (part I) or three
      groups (part II). No significant differences were noted in pain scores in the
      preoperative, immediate postoperative, or 4-, 8-, 12-, or 24-hour periods among
      any of the groups, including the saline-only control groups; in either part I or
      part II of the study. Significant differences (P < .01), however, were noted in
      nausea and vomiting scores. Fifty percent (50%) of patients receiving MS vomited,
      while no patients in the saline groups vomited. This study calls into question
      the usefulness of PCA with MS in maxillofacial surgery patients. Pain control was
      questionable at best, and the rate of emesis was unacceptably high in patients
      with potentially compromised airways. Further research is required to determine
      if other analgesics provide better pain control with less nausea in the PCA
      system or if antiemetics can effectively be used to lower the incidence of nausea
      and vomiting.

PMID- 8295051
TI  - Autologous fibrin adhesive in mandibular reconstruction with particulate
      cancellous bone and marrow.
AB  - Displacement of bone graft particles during their placement, neck flap closure,
      and insertion of the freeze-dried mandibular crib housing the graft to the
      glenoid fossa is a commonly encountered problem during major mandibular
      reconstruction with autogenous particulate cancellous bone and marrow. Autologous
      fibrin adhesive proved to be a solution as demonstrated in a series of 33 cases.
      In addition to adhesive and hemostatic properties, it helped the remodeling
      process begin about 50% earlier by providing the substratum for migration of
      mesenchymal cells, accelerating revascularization and migration of fibroblasts,
      stimulating the growth of both fibroblasts and osteoblasts, and slowing the
      multiplication of microorganisms. Bony incorporation and remodeling were detected
      radiographically at the fourth postoperative week compared with the eighth week
      in bone grafts without autologous fibrin adhesive.

PMID- 8295052
TI  - Histomorphometric examination of healing around hydroxylapatite implants in 60Co
      irradiated bone.
AB  - The purpose of this study was to histomorphometrically evaluate the use of
      hydroxylapatite (HA) implants in 60Co-irradiated bone. HA implants were installed
      in rabbit mandibles 3 months, 6 months, and 12 months after 15-Gy irradiation.
      Nonirradiated rabbits served as controls. The rabbits were killed 7, 14, 30, 60,
      and 90 days after the HA implantation. The histologic features of the healing
      process were examined and histomorphometric measurements were made to quantify
      the percentage of HA-bone contact and trabecular bone in the medullary cavity. In
      the irradiated groups, although HA-bone contact was observed later than that in
      the controls, recovery increased with time after irradiation and the rate of HA
      bone contact bone-contacting implant surface ratio; BCSR exceeded 90% in all
      groups examined before 90 days. In the radiated groups, the average trabecular
      bone-specific volume was lower than that in the controls and began to decrease
      before BCSR exceeded 90%. Based on the present data, as well as data from the
      literature, it is suggested that the success rate of HA implants in irradiated
      bone increases with the interval after radiotherapy. It is also recommended that
      HA implants in irradiated bone be installed so that bearing by the cortical bone
      is increased.

PMID- 8295053
TI  - Factors influencing oral and maxillofacial surgeons to select or leave academic
      careers.

PMID- 8295054
TI  - Well-circumscribed recurring facial mass.

PMID- 8295055
TI  - Papillary cystadenoma lymphomatosum of the upper lip: report of case.

PMID- 8295056
TI  - Oral psoriasis: report of case.

PMID- 8295057
TI  - Cervicofacial nocardiosis: report of case.

PMID- 8295058
TI  - Peripheral ameloblastoma with unusual mitotic activity and conflicting evidence
      regarding histogenesis.

PMID- 8295059
TI  - Surgical correction of an aural-temporomandibular joint fistula with a temporalis
      flap.

PMID- 8295060
TI  - Clarification regarding the use of ASBA in third molar sockets.

PMID- 8295061
TI  - More on hemangiomas in patients with Maffucci's syndrome.

PMID- 8295062
TI  - Incidence of solitary intraosseous neurofibroma of the maxilla.

PMID- 8295063
TI  - [Vestibular changes due to barotrauma].
AB  - Morphological vestibular changes caused by barotrauma were studied in guinea
      pigs. Animals were exposed to rapid decompression from 2 absolute atmospheric
      pressures (ATA) to 1 ATA, which causes inner ear barotrauma in the guinea pig.
      During decompression, spontaneous nystagmus was recorded, which consisted of
      irritative symptoms initially, followed by paralytic nystagmus. After pressure
      loading and observation to confirm the absence of Preyer's reflex with vertigo,
      the animals were tested for caloric nystagmus using ice water and then sacrificed
      at varying intervals. Then, morphological changes in vestibular organs and the
      organ of Corti were studied. Half of the experimental animals showed canal
      paresis on caloric testing. Damage to the organ of Corti was severe while that to
      vestibular organs was very slight. Damage to the sensory cells of the vestibular
      organs was not clear on light microscopy, despite a partial collapse of
      labyrinthine membranes. Under scanning electron microscopy, local damage was
      observed in a portion of the crista ampullaris of the semicircular canals. In
      this area, incomplete or complete disappearance of kinocilia and stereocilia,
      similar to that seen after rotatostimulation, was observed. However, no damage to
      sensory hairs was seen in the utricles and saccules. The observed vestibular
      organ damage, resulting from inner ear barotrauma, suggested effects on
      endolymphatic flow.

PMID- 8295064
TI  - [Further study of Schellong testing in 152 young females].
AB  - Orthostatic dysregulation (OD) generally implies a systemic condition indicating
      poor circulatory function resulting from autonomic imbalance, which usually
      appears in a rather young population at or around puberty, predominantly in
      females. This condition can be recognized from the results of a questionnaire
      which has been proposed and prepared by the Pediatric OD Study Group of Japan as
      diagnostic criteria for OD. Schellong testing has also been developed as a
      screening method to determine OD or orthostatic hypotension. We carried out a
      survey and analyzed data collected with the questionnaire and Schellong test
      results among 152 young normal females ranging in age from 18 to 21 years in
      order to obtain the actual prevalence of OD in these subjects. Among 152 young
      normal females, 39 (25.7%) were confirmed to have OD based on the questionnaire.
      Although orthostatic dizziness was relatively common in this series of young
      females, regardless of the presence or absence of OD (90/152, 59.2%), this
      symptom, which is listed as one of the 5 major items on the questionnaire, was
      much more prevalent in subjects with OD (37/39, 94.9%). Similar prevalence
      patterns for fatigability or unexplained tiredness were also found in subjects
      with OD (28/39, 71.8%) when compared with total subjects (55/152, 36.2%). As for
      the positive rate of the Schellong test, subjects with and without OD showed
      33.3% and 31.3%, respectively, and this difference was not statistically
      significant. There was, however, a highly significant difference in the fall in
      systolic pressure during the Schellong test procedure between subjects without OD
      and 10 subjects with OD in whom orthostatic dizziness frequently
      occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295065
TI  - [Extratympanic electrocochleography during the glycerol dehydration test in
      control subjects with normal hearing].
AB  - Extratympanic electrocochleography with click stimulation at 80 dBnHL was
      performed in 15 subjects with normal hearing (28 ears) during the glycerol
      dehydration test. Testing was performed before oral administration of glycerol
      (1.2 ml/Kg) as well as after 1, 2, and 3 hours. The mean electrocochleography
      response from 12 recordings was determined to obtain stable values. Although some
      ear action potential (AP) amplitudes increased at 1 hour after administration,
      the AP amplitudes gradually decreased during the test. There were significant
      differences between before and at 2 and 3 hours after administration. Summating
      potential (SP) amplitudes increased slightly, but there were no significant
      differences between before and each time after glycerol administration. Negative
      SP/AP ratios gradually increased during the test, and there were significant
      differences between before and each time after glycerol administration.
      Laterality of the glycerol-induced changes in 13 subjects having both ears tested
      was positive at 1 and 2 hours after glycerol administration, but the laterality
      had diminished by 3 hours after administration. It was thus reasonable to compare
      both ears at 3 hours after glycerol administration.

PMID- 8295066
TI  - [Expression of epidermal growth factor receptor in squamous cell carcinoma of the
      head and neck].
AB  - Localization of epidermal growth factor receptor (EGFR) was investigated
      immunohistologically in 68 untreated patients with squamous cell carcinoma of the
      head and neck regions. These patients consisted of 16 with cancer of the lips and
      mouth, seven with mesopharyngeal cancer, six with epipharyngeal cancer, 15 with
      hypopharyngeal cancer, 10 with laryngeal cancer, 12 with maxillary cancer and two
      with other tumors (cancer of the auricle and cancer of the eyelid in one patient
      each). The patients consisted of 57 men and 11 women, with a mean age of 60
      years. In cases with a normal oral mucosa, marked expression of EGFR was observed
      in the epithelial cell membrane, while expression decreased toward the luminal
      surface. Cancer cells also showed positive staining of EGFR in all patients, but
      the intensity of staining was inconsistent among them. Among the 32 patients in
      whom the staining intensity of EGFR was equal to or weaker than that in basal
      cells of the normal oral mucosa, 12 patients had lymph node metastasis. Twenty
      eight of the 36 patients in whom the staining was stronger than that in the
      normal cells had lymph node metastasis, suggesting that overexpression of EGFR in
      carcinoma cells is a risk factor for lymph node metastasis of head and neck
      cancers (P < 0.005). On the other hand, there were no obvious relationships
      between either the size or the degree of keratinization of the primary lesion and
      EGFR expression.

PMID- 8295067
TI  - [Morphological study of intra-laryngeal ganglia and their neurons in the cat].
AB  - The distribution, number, projections and nature of ganglia and ganglionic
      neurons in the feline larynx were investigated morphologically. Six to eight
      large oval or spindle-shaped ganglia (including 50-80 ganglionic neurons per
      ganglion) in rostral portions of the paraglottic spaces, four to six small
      spindle-shaped ganglions (containing 5-25 ganglionic perikarya in each ganglion)
      dorsal to the posterior cricoarytenoid muscles and one to three small elliptical
      ganglia (having 15-25 ganglionic cells in each ganglion) around the inferior
      laryngeal nerves were observed in the larynx. Each ganglion was covered with a
      fibrous capsule and ganglionic neurons with a diameter of 25-30 microns totaled
      600 to 800. Ganglionic neurons received projections from the dorsal motor nucleus
      of vagus, the superior cervical ganglion (SCG) and the nodose ganglion (NG)
      ipsilaterally. On the other hand, ganglionic neurons projected to SCG, NG,
      ipsilaterally and the laryngeal mucosa bilaterally with ipsilateral predominance.
      Ganglionic neurons showed acetylcholinesterase positive reactions, presumably
      parasympathetic. On immunocytochemistry, many vasoactive intestinal polypeptide
      (VIP)-immunoreactive (ir) neurons, and a few tyrosine hydroxylase (TH)-ir and
      substance P (SP)-ir cells were recognized in ganglions, but no calcitonin gene
      related peptide (CGRP)-ir neurons were found. These VIP, TH, SP-ir neurons did
      not change after denervation of the ipsilateral superior and recurrent laryngeal
      nerves. Many VIP- and some TH-, SP-, CGRP-ir fibers were also observed around
      vessels and glandular cells. The present findings show that intra-laryngeal
      ganglionic neurons not only have an endogenic cholinergic nature, but are also
      involved in local sympathetic and sensory nervous systems.

PMID- 8295069
TI  - [Evoked otoacoustic emissions: a comparison between responses from humans and
      guinea pigs].
AB  - Transiently evoked otoacoustic emissions (TEOAEs) from 16 normal human ears and
      26 normal guinea pig ears were measured with the ILO 88 (ver 3.91). The following
      results were obtained: 1) In one animal ear, waveforms of TEOAEs were unchanged
      after administration of muscle relaxants, and showed reversible changes before
      and after asphyxia. 2) In 3 guinea pig and 2 human ears, the input-output
      functions showed a strong saturation at higher stimulus levels, when measurement
      of the highest peak-to-peak amplitude was used as the output energy. 3) Highest
      peak frequencies (HPFs) of TEOAEs were distributed at around 1 kHz in human ears
      but were concentrated around frequencies of 2 kHz to 3 kHz in almost all guinea
      pig ears. 4) Latencies of predominant TEOAEs in human and guinea pig ears were
      9.26 +/- 1.89 msec and 2.37 +/- 0.47 msec, respectively. Endpoint times of TEOAEs
      were 16.37 +/- 1.79 msec and 5.74 +/- 1.10 msec, respectively. Both indicators in
      human ears were 3-4 times longer than those in guinea pig ears. From these
      results, we conclude that click-evoked TEOAEs can be detected even in guinea
      pigs. In addition, our measurements showed that HPFs of TEOAEs in guinea pig ears
      were higher than those in human ears, and that latencies and durations in guinea
      pig ears were much shorter than those in human ears. The higher HPFs of TEOAEs in
      guinea pig ears may be attributable to higher resonant frequencies in the middle
      ear than are found in human ears.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295068
TI  - [Immunohistochemical study of borderline thyroid lesions with special reference
      to relationships among nuclear features, type IV collagen and malignancy of
      follicular lesions].
AB  - It is very difficult to differentiate follicular adenoma from follicular
      carcinoma in thyroid follicular lesions. The authors investigated the biological
      behavior of these thyroid follicular lesions using immunohistochemical
      techniques. Specimens taken from normal thyroid, 2 cases; follicular adenoma, 9;
      atypical adenoma, 7; and follicular carcinoma, 8; were observed. Proliferating
      cell nuclear antigen (PCNA) is a marker of cellular proliferation. Nucleoli are
      also increased in number and move to the nuclear margin in cases of cellular
      proliferation. The PCNA labeling index was calculated by counting the number of
      PCNA-positive cells per 2,000 tumor cells. PCNA labeling indices were 0.025% in
      the normal thyroid, 1.41% in follicular adenoma, 5.73% in atypical adenoma, and
      6.16% in follicular carcinoma, respectively. Nucleoli retaining rate of the tumor
      cells were 40.0% in follicular adenoma, 63.7% in atypical adenoma, and 71.8% in
      follicular carcinoma. Rates of nucleolus margination were 20.9% in follicular
      adenoma, 34.4% in atypical adenoma, and 36.0% in follicular carcinoma. Changes in
      the basement membrane were morphologically classified into three groups as
      follows; membrane structure almost preserved (group I), partial discontinuity
      (breaks) (group II), and widespread absence of membrane structure (group III),
      based on immunohistochemical investigation of Type IV collagen. Group I was
      demonstrated in 8 cases of follicular adenoma and one case of atypical adenoma.
      Group II was observed in one case of follicular adenoma, 3 cases of atypical
      adenoma and 3 cases of follicular carcinoma. In addition, group III was noted in
      3 cases of atypical adenoma and 5 cases of follicular carcinoma.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8295070
TI  - [A case of middle ear adenoma].
AB  - Middle ear adenomas are rare and difficult to diagnose. Recent histological
      studies suggest the presence of a distinct disease entity known as a middle ear
      adenoma. A 16-year-old boy with a middle ear tumor was treated by partial
      temporal bone resection, and the tumor was removed by a combined method using the
      middle cranial fossa and infratemporal fossa approaches. Histological and
      immunohistochemical studies on this tumor showed the findings of a benign
      adenoma. Left facial palsy was noted postoperatively, but it subsequently
      recovered almost completely.

PMID- 8295071
TI  - [Combined treatment of head and neck cancers by radiation therapy and
      chemotherapy with a small dose of CDDP].
AB  - Two-route infusion chemotherapy with a smaller dose of CDDP was applied for
      combined modality treatment with radiation therapy for head and neck cancer from
      1985 to 1992. To determine the appropriate dose of CDDP in this treatment, we
      investigated parameters concerned with its toxicity by comparing two groups given
      5 and 10 mg of CDDP as a daily dose. Complete response was attained in 18 of 24
      cases in the 5 mg group and 8 of 11 cases in the 10 mg group. The toxicity due to
      CDDP in this protocol was found generally to be slight in both groups. Among the
      parameters of toxicity, creatinine clearance was most affected. A decrease in 24
      hr. creatinine clearance was noted in 15 of 29 cases in the 5 mg group and 10 of
      12 cases in the 10 mg group. We had to discontinue this treatment after the first
      course because of lowered creatinine clearance in a patient in the 5 mg group.
      Stomatitis due to radiation therapy appeared to become worse in combination with
      this chemotherapy. The 10 mg dose of CDDP can be applied as a safe combination
      treatment with radiation therapy for head and neck cancer. To improve the outcome
      of this treatment modality for carcinomas of the tongue and oral floor, the 10 mg
      dose of CDDP was thought to be more beneficial. However, in the case of
      cumulative doses of CDDP over 100 mg, precaution should be taken to avoid the
      risk from the toxicity of more CDDP administration.

PMID- 8295072
TI  - [The histogenesis and malignant transformation of inverted papilloma on the sino
      nasal cavity--in comparison with inverted papilloma on the urinary bladder].
AB  - Inverted papilloma on the sino-nasal cavity (IP on SN) is a rare benign tumor.
      However, local recurrence and distant metastasis do occasionally occur. The
      histogenesis and histological prospects for the biological behavior of this tumor
      are still unknown. To clarify these issues, we histologically studied 25 cases of
      IP on SN and 10 cases of IP on the urinary bladder (IP on UB), which were
      biopsied or resected in the National Shikoku Cancer Center Hospital. Since, with
      regard to aspects of histogenesis such as metaplasia, dysplasia and malignant
      transformation, there were some similarities and differences between these two
      benign tumors. Biopsied or resected specimens were microscopically examined with
      hematoxylin-eosin (HE), periodic acid-Shiff (PAS), and Azan stains. Sixteen of 25
      IP on SN presented a typical inward growth Pattern and 9 cases were
      simultaneously associated with an exophilic proliferation pattern. In cases of IP
      on UB, a typical inverted growth Pattern was observed in 3 cases. Seven of 10 IP
      on UB showed a complex of inward and exophilic patterns. Subsequently, we focused
      on metaplasia of IP, probably caused by certain physiological, chemical and
      inflammatory stimuli. All IP on SN bore squamous metaplasia and 5 cases
      simultaneously showed features of transitional metaplasia. Often, these two types
      of metaplasia were observed in the submucosal glands. In IP on UB, 7 of 10 cases
      showed squamous metaplasia and 9 cases presented intestinal metaplasia. These
      metaplastic changes were also found in Brunn's nest. Furthermore, the metaplastic
      epithelium in 24 IP on SN demonstrated stratified proliferation, atypical nuclei
      and/or mitosis which were considered to be evidence of malignancy. In fact, 9 of
      25 IP on SN partially contained a component of squamous cell carcinoma and 7
      cases out of 10 IP on UB showed features of transitional carcinoma in a portion
      of the papilloma lesion. This evidence suggests that both IP on SN and IP on UB
      originate in submucosal glands, specifically exocrine glands in the sino-nasal
      region and Brunn's nest in the urinary bladder. Also, in these glands,
      metaplastic change was commonly seen, and occasionally revealed malignant
      features such as squamous cell carcinoma in the sino-nasal cavity and
      transitional carcinoma in the urinary bladder. We finally concluded that the
      process of growth and the mechanism of malignant transformation might be similar
      between IP on SN and IP on UB and metaplastic change might play an important role
      in the malignant transformation of IP on SN and IP on UB.

PMID- 8295073
TI  - [Diurnal sleep study for sleep related breathing disorders--comparative study of
      diurnal polysomnography using diazepam with nocturnal polysomnography].
AB  - Nocturnal polysomnography (n-PSG) and diurnal polysomnography using diazepam (d
      PSGD) were performed on 46 patients with sleep related breathing disorders
      including sleep spnea syndrome (SAS) patients and simple snorers. Sleep stage,
      apnea type, and various indices of breathing disorders were examined, and the
      results obtained by the two different sleep studies were compared. There were no
      significant differences in either the apnea type or the indices of breathing
      disorders between the two sleep studies. Concerning the sleep stage, significant
      differences in the duration of REM sleep between the two sleep studies were
      observed. In the duration of each stage of NREM sleep, however, there were no
      significant differences. Also, no significant differences were observed in the
      indices of breathing disorders between SAS patients and simple snorers. IN
      CONCLUSION: d-PSGD can be utilized as a substitute for n-PSG clinically, in
      patients with sleep related breathing disorders, as far as the study of NREM
      stages is concerned.

PMID- 8295074
TI  - Identification of linotte, a new gene affecting learning and memory in Drosophila
      melanogaster.
AB  - We describe the identification of linotte, a new autosomal gene in Drosophila
      involved with learning and memory. The linotte mutant was derived from a PlacW
      transposon mutagenesis and was screened for three-hour memory deficits after
      classical conditioning of an olfactory avoidance response. Sensory and motor
      systems (olfactory acuity and shock reactivity) required for the classical
      conditioning experiments were normal in mutant linotte flies--indicating that the
      mutation disrupts learning/memory specifically. A chromosomal deficiency of the
      37D region, where the linotte P insert was localized in situ, failed to
      complement linotte's memory defect, and flies from two lines homozygous for
      independent PlacW excisions show normal memory--indicating that the P insertion
      is responsible for the mutant phenotype. Additional behavior-genetic data suggest
      that linotte gene is non-vital.

PMID- 8295075
TI  - Differential modulation of potassium currents by cAMP and its long-term and short
      term effects: dunce and rutabaga mutants of Drosophila.
AB  - The cAMP concentration in Drosophila is increased by mutations of the dunce (dnc)
      gene and decreased by mutations of the rutabaga (rut) gene. Such mutants provide
      a unique means for exploring the role of cAMP in functional and developmental
      regulation of membrane currents. Four distinct K+ currents have been identified
      in Drosophila larval muscle fibers, i.e. the voltage-activated transient IA and
      delayed IK and the Ca(2+)-activated fast ICF and slow ICS. Results from our
      voltage-clamp studies indicated that both IA and IK were increased in dnc
      alleles. Normal muscle fibers treated with dibutyryl-cAMP showed a similar
      increase of IA, but no significant effect on IK. In contrast to the dnc alleles,
      the rut mutations appeared to enhance ICS greatly while leaving the amplitude of
      other currents largely unchanged. In addition, the dibutyryl-cAMP-induced
      increase in IA was not observed in rut fibers. Caffeine and W7, which are known
      to interfere with several second messenger pathways, also modulated K+ currents
      in larval muscle fibers. The currents in dnc and rut fibers showed strikingly
      altered responses to caffeine and W7. The results demonstrate that the various K+
      currents in Drosophila muscles are affected by altered cAMP cascades in the
      mutants. The fact that not all dnc and rut mutant defects can be mimicked or
      reversed by acute application of cAMP suggests that long-term modulation of K+
      currents by cAMP may involve mechanisms distinct from the short-term effect of
      cAMP.

PMID- 8295076
TI  - Analysis of the antennal phenotype in the Drosophila mutant lozenge.
AB  - Previous work on the lozenge (lz) gene complex of D. melanogaster has focused on
      the compound eye. Here we study the effects of 22 lz mutations on the antennal
      sensilla. The antenna of strong lz alleles is characterized by a lack of
      basiconic sensilla and by a significantly increased density of coeloconic
      sensilla. Intermediate alleles have few basiconic sensilla, they exhibit a highly
      increased density of trichoid sensilla, but a normal coeloconic density.
      Basiconic sensilla on the maxillary palps are weakly affected even by strong lz
      alleles. The antennal phenotype for most of the strong and intermediate mutants
      is partially dominant over wild type. Although this complicates the
      interpretation of complementation data, 12 selected mutants that were studied in
      heteroallelic combinations seem to define a single cistron. Temperature shifts of
      the lztsl allele showed that gene activity is crucial from about 87% of the third
      larval instar up to 7% of pupal life. Applying restrictive temperature early
      during this period results in a 'novel' phenotype that is characterized by a
      dramatic decrease in the density of trichoid sensilla, whereas a late pulse of
      restrictive temperature leads to a 'normal' intermediate phenotype. Our data
      suggest that the lz gene controls at least five different functions in the
      antenna: the size of the third antennal segment, the overall number and density
      of sensilla, the proportions of the 3 types of sensilla, and the generation of
      basiconic sensilla.

PMID- 8295077
TI  - Differential effects of dunce mutations on associative learning and memory in
      Drosophila.
AB  - Initial learning, 30- and 180-min memory retention after Pavlovian conditioning
      of an odor avoidance response was quantified in dnc1, dnc2, dncM11 and Canton-S
      (wild-type) homozygotes and in dnc1/FM7, dnc2/FM7, dncM11/FM7, dncM11/Can-S, Can
      S/FM7, dnc1/dncM11 and dnc2/dncM11 heterozygotes. Our results consistently showed
      that a) the dunce mutations are semi-dominant for initial learning and b) genetic
      variants carrying the enzymatically hypomorphic dnc2 mutation produce learning
      scores lower than those of the amorphic dncM11. Analysis of this particular set
      of retention intervals, using a modified statistical model designed to evaluate
      decay rates, revealed no discernable effects of the dunce mutations on memory
      formation 30 to 180 min after training. These results are consistent with a model
      of memory formation, in which dunce is hypothesized to disrupt acquisition and/or
      short-term memory.

PMID- 8295078
TI  - Toward a family-centered pediatric psychology--challenge and opportunity in the
      international year of the family.

PMID- 8295079
TI  - Psychological adjustment of mothers of children and adolescents with sickle cell
      disease: the role of stress, coping methods, and family functioning.
AB  - Assessed the psychological adjustment of 78 mothers of children and adolescents
      (7-17 years of age) with sickle cell disease. Support was provided for a
      transactional stress and coping model in delineating the processes associated
      with maternal adjustment. In particular, poor maternal adjustment was associated
      with use of palliative coping methods and high levels of stress related to daily
      hassles. Variables of the model accounted for 55% of the variance in maternal
      psychological distress.

PMID- 8295080
TI  - Psychological factors affecting reported pain in juvenile rheumatoid arthritis.
AB  - Examined the extent to which psychological variables are correlated with pain
      reported by children with juvenile rheumatoid arthritis (JRA). In a hierarchical
      multiple regression analysis with pain as the dependent variable, four
      psychological measures of child and family functioning resulted in a significant
      increase in R2 = .31, p < .0001, after the effects of disease characteristics
      were considered. Greater emotional distress in the child, greater emotional
      distress of the mother, and greater family harmony were related to higher
      reported pain. Findings suggest that more attention should be given to
      nonpharmacological aspects of pain and pain management in children with JRA.

PMID- 8295081
TI  - Enhanced parenting knowledge and skills in mothers of preschool children with
      sickle cell disease.
AB  - Compared 25 preschool children with sickle cell disease (SCD) to demographically
      matched healthy comparison children on maternal reports of child-rearing beliefs
      and practices and maternal and child behaviors related to social adjustment.
      Mothers of children with SCD possessed significantly more knowledge of
      appropriate discipline techniques. The groups did not differ on maternal reports
      of socially relevant child behavior. However, when mother-child interactions were
      observed in free play and structured play settings, mothers of children with SCD
      treated their children as competent significantly more, and treated their
      children as incompetent significantly less, than comparison mothers. Mothers of
      children with SCD also used significantly more reinforcement during the final toy
      pick-up condition. There were no observed differences between groups in the
      children's behavior.

PMID- 8295082
TI  - Effects of maternal distraction versus reassurance on children's reactions to
      injections.
AB  - Manipulated experimentally mothers' verbal behavior during a routine
      intramuscular injection in order to help clarify the role of nonprocedural talk
      (distraction) and parental reassurance on children's reaction to the injection.
      42 child-mother dyads were recruited from a general pediatric primary care clinic
      and were randomly assigned to a parental reassurance, parental nonprocedural talk
      (distraction) or minimal-treatment control group. Children in the maternal
      distraction condition exhibited significantly less distress during the
      immunization injection than those in the reassurance and control conditions.
      Specifically, children in the maternal distraction group exhibited less crying
      than children in the other two groups. Children in the reassurance and control
      groups did not differ from each other in terms of behavioral distress. The
      present findings serve further to bolster the evidence for the efficacy of
      maternal distraction as a way to ameliorate child distress during invasive
      medical procedures.

PMID- 8295083
TI  - Sickle cell disease pain in children and adolescents: change in pain frequency
      and coping strategies over time.
AB  - Examined 9-month follow-up data obtained from children and adolescents with
      sickle cell disease (SCD) and their parents participating in a longitudinal study
      of pain coping strategies. Of 87 subjects completing the baseline assessment of
      pain coping strategies, 70 (80%) of their parents completed a structured pain
      interview assessing their child's health care use and activity reduction during
      painful episodes over the follow-up period. Regression analyses controlling for
      age and pain frequency revealed that baseline Coping Attempts were associated
      with higher levels of school, household, and social activity during painful
      episodes. Baseline Passive Adherence was associated with more frequent health
      care contacts during the subsequent 9 months. Increases in Negative Thinking over
      time were associated with further increases in health care contacts during the
      follow-up period. Comparing pain coping strategies assessed at baseline to pain
      coping strategies measured at follow-up revealed that pain coping strategies were
      relatively stable over time for younger children but changed more for
      adolescents.

PMID- 8295084
TI  - Oral discourse after early-onset hydrocephalus: linguistic ambiguity, figurative
      language, speech acts, and script-based inferences.
AB  - Studied 101 children, ages 6 to 15 years (50 with early-onset hydrocephalus, 51
      normally developing), on four oral discourse tasks: establishing alternate
      meanings for ambiguous sentences; understanding figurative expressions; making
      bridging inferences; and producing speech acts. Children with hydrocephalus
      performed more poorly than controls on all four discourse tasks; and a higher-IQ
      hydrocephalus subgroup performed more poorly than controls on all but the
      figurative expressions task. The fluent, grammatically framed, but content
      impoverished language described in early-onset hydrocephalus appears to reflect
      not so much problems in deriving word- and sentence-based meaning as deficits in
      the pragmatic use and understanding of language in discourse.

PMID- 8295085
TI  - Marginal periodontitis and cytokines: a review of the literature.
AB  - Recent research on the immunopathogenesis of marginal periodontitis has focused
      on cytokines, because these mediators govern biological activities in
      inflammatory tissue destruction. Several studies have been carried out to
      elucidate the involvement of cytokines in periodontitis, including cytokine
      measurements in samples from gingival tissue, gingival crevicular fluid, and in
      supernatants of stimulated in vitro grown cells from gingival tissue and
      peripheral blood. The results, summarized in this review, suggest that cytokines
      are involved in the progress of periodontitis. Furthermore, cytokines may be
      valuable as markers of tissue breakdown. At the present stage, however, there are
      difficulties in detecting and quantifying cytokines by immunochemical methods
      and, in particular, by bioassays. Increased knowledge of the cytokine network may
      open new pathways of periodontitis treatment by controlling processes involved in
      tissue breakdown.

PMID- 8295086
TI  - The clinical effectiveness of open versus closed scaling and root planing on
      multi-rooted teeth.
AB  - Scaling and root planing are the most common techniques utilized to achieve a
      biologically-acceptable root surface. Thorough root debridement is a demanding
      task, with residual deposits of plaque and calculus a not uncommon finding after
      instrumentation. This study evaluated the effectiveness of scaling and root
      planing via a closed versus an open flap approach. Sixty multi-rooted teeth were
      assigned to one of three groups: untreated controls, closed scaling/root planing,
      and open flap scaling/root planing. Following debridement, teeth were extracted,
      immersed in methylene blue, and examined for the percent surface area having
      stainable residual deposits. The mean percent stained surface area covered by
      residual plaque and calculus was 54.3% in the closed root planing group compared
      to 33.0% in the open flap root planing group. The untreated control teeth had
      91.0% of the root surface covered with stainable deposits. Within-group
      comparisons showed no significant difference in the percent stained residual
      plaque and calculus in shallow areas of the pocket (< or = 3 mm apical to the
      gingival margin) compared to deeper areas (> 3 mm subgingival). Examination of
      furcation regions demonstrated heavy residual stainable deposits for both
      treatment methods, with no significant differences between techniques. There was
      no correlation between the time spent in root debridement and the percent
      residual deposit area. The results demonstrate that hand instrumentation alone is
      inadequate for thorough debridement of furcations and suggest that new approaches
      are needed to provide a root surface which is compatible with formation of new
      periodontal attachment. High frequency ultrasonic instruments, rotary burs, and
      chemical agents may assist in debridement of such surfaces.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8295087
TI  - Impact of microbiological consultation on clinical decision making: a case
      control study of clinical management of recurrent periodontitis.
AB  - Data obtained from diagnostic tests may influence the clinician's perception of
      the patient's state and in some instances may alter subsequent choices of
      therapeutic interventions. To determine if microbiological consultation
      influences the clinical management of patients with recurrent periodontitis, an
      observational, case-control study was conducted to measure the amount and type of
      periodontal treatment provided by periodontists (n = 13) who had referred
      patients with recurrent periodontitis for microbiological consultation. The
      control group consisted of periodontists (n = 10) who had not referred recurrent
      periodontitis patients for testing. Patients (n = 31; 20 females, 11 males; mean
      age 49.8 +/- 10.0 years) treated by the case group of periodontists were matched
      for age and sex to patients (n = 48; 22 females, 26 males; mean age 49.9 +/- 8.5
      years) treated by the control group of periodontists. Questionnaires were
      administered to quantitatively assess the amount and type of treatment before and
      after receiving the microbiological report. Specific analyses were performed as a
      function of the time of receipt of the microbiology report. Case-control
      differences prior to the receipt of the report indicated that the amount of
      surgery/year was 43% greater for controls (P < 0.04), in spite of control
      patients exhibiting fewer deep pockets than case patients (P < 0.05). Case
      control differences after the receipt of the report indicated that case patients
      were provided with 45% greater number of appointments/year (P < 0.005), 46%
      greater scaling/year (P < 0.02), and 79% greater antibiotics/year (P < 0.01)
      compared with controls. The report influenced 9 (69%) case periodontists to
      change treatment. Case patients who received a change in treatment (n = 21)
      exhibited greater number of deep pockets at the time of entry into the study (P <
      0.05) as compared with case patients who did not receive a change in treatment.
      Paired t-tests of differences within groups before and after the report
      demonstrated that case patients had a significant increase in treatment after the
      report as shown by 22% greater number of visits/year (P < 0.05) and 54% greater
      number of antibiotic prescriptions/year (P < 0.01). In contrast, controls
      demonstrated no significant change in treatment. Further, contrasts of change in
      treatment before and after the report again indicated that case patients
      exhibited a significantly higher number of visits/year (P < 0.04) and number of
      antibiotic prescriptions/year (P < 0.02) compared with control patients.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8295088
TI  - Evaluation of ferric oxalate as an agent for use during surgery to prevent post
      operative root hypersensitivity.
AB  - The aim of this study was to evaluate the effectiveness of a 6% ferric oxalate
      solution applied during periodontal surgery to prevent post-operative tooth
      hypersensitivity. Twenty-five adult patients with similar bilateral periodontal
      defects participated in this study. Data were collected at baseline (1 week prior
      to surgery) and 1, 2, 4, and 6 weeks following surgery. Sensitivity level was
      determined using the visual analog scale (VAS) with the following stimuli: 1)
      mechanical stimulation with a No. 23 dental explorer; 2) water at 50 degrees C;
      3) ice; and 4) electric pulp tester (EPT). Teeth were randomly assigned to either
      test (6% ferric oxalate in 0.9% saline) or control (0.9% saline) groups.
      Solutions were applied to the exposed root surfaces for 1 minute during surgery.
      Data were analyzed by repeated measures ANOVA, paired t-test, and Pearson's
      correlation test. Results from this study demonstrated statistically significant
      reduction in the responses to thermal stimuli, especially cold, between groups
      treated with ferric oxalate as compared to those treated with saline. For the
      cold test the difference increased with time from baseline to 6 weeks.
      Statistically significant (P < 0.05) differences in sensitivity to heat between
      groups were also observed, but only at 2 and 4 weeks following surgery. There
      were no differences at any time period between the test and control groups when
      tactile or EPT techniques were used. In addition, there was no correlation
      between sensitivity and other clinical parameters. It was concluded from this
      study that 6% ferric oxalate was effective in reducing post-surgical cold
      sensitivity when applied during periodontal surgical procedures.

PMID- 8295089
TI  - An in vitro study of dentinal tubule occlusion by ferric oxalate.
AB  - This study examined ferric oxalate's ability to occlude dentinal tubules both in
      the presence of a smear layer and after its removal. Radicular dentinal chips
      were prepared with a smear layer created from a high speed carbide bur. The
      dentinal chips were then grouped as follows: 1) those with the smear layer
      remaining intact; 2) those sonicated for 7 minutes; 3) those treated with 10%
      tetracycline HCl; 4) those treated with 0.5M EDTA; 5) those treated with 20%
      citric acid; or 6) those treated with saturated citric acid. Six percent ferric
      oxalate was applied for 1 minute to the dentinal chips under blinded conditions.
      The chips were examined under SEM and the number of small and large crystals
      formed were counted. The results indicate that a decrease in the number of small
      crystals occurs following pretreatment of the smear layer by chemical means. An
      increased variability in size and shape of the crystals is also observed when no
      chemical pretreatment is used. Thus, relative to the number of crystals that
      form, no chemical pretreatment of radicular dentin is indicated prior to
      application of ferric oxalate in the treatment of root sensitivity.

PMID- 8295091
TI  - Closure of oroantral communication using guided tissue regeneration and an
      absorbable gelatin membrane.
AB  - Surgical intervention into the maxillary posterior area can lead to inadvertent
      communication with the maxillary sinus. Spontaneous healing of 1 to 2 mm openings
      can occur. However, in patients with larger oroantral communications and those
      with a history of sinus disease, surgical closure is often indicated. Acute and
      chronic oroantral fistula and sinusitis can occur as a result of inadequate
      treatment. The most common causes of complications include inadequate site
      preparation, flap closure, flap necrosis, infection, and patient non-compliance.
      A technique for the closure of oroantral communications using guided tissue
      regeneration is described. This technique utilizes an absorbable gelatin film
      (membrane), allogenic bone graft material (DFDBA), and non-resorbable expanded
      polytetrafluoroethylene (ePTFE) membrane. The gelatin membrane prevents
      displacement of graft material into the antrum and sinus epithelial cell
      migration, while the ePTFE membrane promotes selective cell population with
      subsequent regeneration of the osseous wall of the oroantral defect.

PMID- 8295090
TI  - Guided tissue regeneration with dentin biomodification.
AB  - This study was undertaken to provide histologic observations on the effectiveness
      of citric acid and tetracycline HCl root surface demineralization when used in
      conjunction with guided tissue regeneration (GTR) procedures. Eight beagle dogs
      with naturally-occurring periodontitis were initially treated with scaling and
      root planing. Four weeks later, 12 mandibular quadrants were treated surgically
      with modified Widman flap and expanded polytetrafluoroethylene (ePTFE). The teeth
      in 4 of the quadrants were randomly root conditioned with tetracycline HCl, while
      those in 4 additional quadrants were randomly treated with citric acid. ePTFE
      membranes were sutured in place. The beagles received prophylaxis (chlorhexidine
      and toothbrushing) 3 times a week. After 6 weeks, the membranes were removed;
      prophylaxes continued for 4 months. Histological evaluation revealed new cementum
      on the root surfaces. A new periodontal ligament with fibers inserting into the
      new cementum was noted. Statistical evaluation of the buccolingual measurements
      demonstrated membranes alone resulted in significantly more new connective tissue
      and new bone formation than membranes with root conditioning agents. Within the
      furcation, no significant differences were found. However, there was a trend for
      more bone formation with membranes alone. Within the limits of this study it may
      be concluded that GTR utilizing an ePTFE membrane results in new connective
      tissue attachment and bone regeneration in the beagle dog. Root surface
      demineralization with citric acid or tetracycline HCl does not enhance the
      results achieved with GTR when used alone.

PMID- 8295092
TI  - Effect of a sodium benzoate-sodium bicarbonate compound on dental plaque
      formation.
AB  - The objective of this study was to evaluate the effect of a sodium benzoate
      sodium bicarbonate (SBSB) compound on dental plaque formation and developing
      gingivitis. Eighteen subjects were given a prophylaxis and instruction in oral
      hygiene to establish plaque-free conditions and gingival health for the study
      baseline. They were randomly divided into three groups. Each participant was
      instructed to rinse twice daily with either a 0.15% chlorhexidine digluconate
      solution, the SBSB compound, or a placebo solution for 21 days. They refrained
      from all other oral hygiene procedures during this period. Plaque, gingival, and
      stain indices were scored at baseline and at days 7, 14, and 21 during the
      rinsing protocol. A significant increase in plaque accumulation was observed for
      the SBSB compound and placebo groups in days 7 through 21. No increase in plaque
      accumulation was observed in the chlorhexidine group. An increase in gingival
      inflammation was observed in all groups, with no significant differences between
      groups. Significant increases in gingival bleeding occurrence compared to
      baseline were found in the chlorhexidine group by day 21, in the SBSB compound
      group by day 7, and in the placebo group by day 14. The present study did not
      disclose any plaque or gingivitis inhibiting effects of the SBSB compound.

PMID- 8295093
TI  - Oral hygiene status and necrotizing ulcerative gingivitis in Nigerian children.
AB  - This study was designed to determine the association between oral hygiene status
      and necrotizing ulcerative gingivitis (NUG), as well as the severity of NUG in
      Nigerian children. The study cohort was made up of 438 children under 12 years
      attending the Dugbe Dental Centre in Ibadan, Nigeria. A dental history and intra
      oral examination using probe and mirror were taken. A slightly modified Green and
      Vermillion index was used to determine oral hygiene status. An index was also
      developed for NUG severity. The result showed that only 2.4% of the children with
      good oral hygiene had NUG, compared with: 24.6% of those with fair oral hygiene;
      62.8% of those with poor oral hygiene; and 66.7% of those with very poor oral
      hygiene. The prevalence of the more severe stages of the disease showed an
      increasing trend as the oral hygiene status became poorer. This study thus
      demonstrated that the prevalence of NUG was significantly higher and more severe
      in children with poor oral hygiene status compared with those having good oral
      hygiene status. (P < 0.001).

PMID- 8295094
TI  - Effects of sex hormones on production of prostaglandin E2 by human peripheral
      monocytes.
AB  - The effects of sex hormones on the vitro production of prostaglandin (PG) E2 by
      monocytes were investigated. Monocytes were obtained from heparinized peripheral
      blood of healthy adults and incubated for 24 hours with lipopolysaccharide (LPS)
      and sex hormones. After incubation, the medium was assayed for PGE2 by means of
      radioimmunoassay. PGE2 production by monocytes was enhanced by progesterone.
      Estradiol reduced PGE2 production at 0.4 ng/ml, but enhanced it at 20 ng/ml.
      Testosterone reduced PGE2 production. The reduced PGE2 production by monocytes
      treated with 0.4 ng/ml of estradiol was restored to the control level by addition
      of progesterone at 20 ng/ml. These results suggest that sex hormones may modulate
      gingival inflammation mediated by PGE2.

PMID- 8295095
TI  - Variation and distribution of periodontists: 1982-1991.
AB  - A review of the past three ADA studies on the distribution of dentists provides
      specific information on the evolving numbers of periodontists at the national,
      regional, and state levels. Findings include: 1) a gradual increase in the ratio
      of periodontist-to-population; 2) 30% of periodontists were less than age 40
      (more than almost all other specialties); and 3) an increasing percent of senior
      dental students anticipate applying to periodontal programs. Although government
      agency and dental profession association projections are available regarding
      major future decreases in the overall number of dentists, limited information is
      available for future periodontist manpower determinations.

PMID- 8295096
TI  - Success and failure rates of cylinder implants in type IV bone.
AB  - It is well documented that implant success rates are much lower in Type IV bone
      than in Types I, II, and III. However, all of these studies have reported on the
      use of screw type implants. The present study demonstrates the efficacy of
      cylinder implant use in Type IV bone. A total of 513 cylinders were placed in
      Type IV bone and were followed for 0 to 60+ months in function. The absolute
      success rate was 95.7%. Of the 22 fixture failures encountered, 8 were discovered
      at the time of second stage surgery, 3 during the first year following
      uncovering, and 11 occurred after 24 to 36 months in function. A possible
      rationale for the higher success rate of cylinders as compared to that reported
      for screw type implants in Type IV bone is presented. Further well-controlled
      studies directly comparing various implant designs in a range of bony sites are
      needed to better understand and to fully document the differences suggested by
      the present study.

PMID- 8295097
TI  - Bone regeneration over a poorly-positioned implant to correct an esthetic
      deformity: a case report.
AB  - Guided tissue regeneration was employed to effect regeneration of a disfigured
      edentulous ridge, with a poorly positioned implant in place. Demineralized freeze
      dried bone and an expanded polytetrafluoroethylene membrane were utilized and
      resulted in growth of new, bone-like material in both a bucco-lingual and apico
      occlusal dimension, totally submerging the unusable implant.

PMID- 8295098
TI  - Ultrastructural features of cyclosporine A-induced gingival hyperplasia.
AB  - The present work collected data on the ultrastructural features of the attached
      gingiva in kidney transplant patients who showed gingival hyperplasia following
      cyclosporin A (Cy A) treatment. Ultrastructural examination was carried out on
      biopsies of attached gingiva obtained from 8 male patients (30 to 60 years old)
      undergoing treatment at the Dental Clinic of the University of Ferrara. The data
      showed that, although many fibroblasts are present in Cy A-induced hyperplasia,
      there is a particular abundance of amorphous substance compared to fibrous, as
      well as marked plasma cell infiltration. On the basis of the data collected, we
      hypothesize that the morphological features of the dimensional increase in
      gingival tissue associated with Cy A treatment in kidney transplant patients may
      be considered local manifestations of a systemic phenomenon.

PMID- 8295099
TI  - Effect of periodontal treatment on gingival overgrowth among cyclosporine A
      treated renal transplant recipients.
AB  - No data exist on any association between combined cyclosporine A (Cy A) and
      dihydropyridine (DHP) medication and the effect of periodontal treatment on the
      occurrence of gingival overgrowth (GO) among renal transplant recipients.
      Clinical data on 27 renal transplant recipients treated with Cy A are presented
      here, including determinations of serum creatinine, whole blood Cy A
      concentration, existence of DHP treatment, and periodontal status. GO was
      classified into four categories according to the clinical changes: score 0 = no
      GO; score 1 = mild GO; score 2 = moderate GO; and score 3 = severe GO. All
      participants received hygiene phase periodontal treatment and gingivectomies were
      performed on 10 who originally had score 2 or 3 GO and pocketing. Fourteen (14)
      of the recipients had no overgrown gingiva or less than at the initial
      examination, and none of them had GO score 2 or 3 at the time of re-examination
      (group A). Thirteen (13) participants had more overgrown gingiva than initially
      or developed score 2 GO after gingivectomies (group B). Group B included
      significantly more DHP-medicated recipients than group A (6/13 and 1/14
      respectively; P < 0.03). The concomitant administration of Cy A and DHP resulted
      in a significantly increased percentage of score 2 overgrown gingival units as
      compared with Cy A alone (P < 0.03). It is concluded that combined treatment with
      Cy A and DHP is a significant risk factor for progression or recurrence of GO
      after periodontal treatment among susceptible patients.

PMID- 8295100
TI  - Osteopromotion: a soft-tissue exclusion principle using a membrane for bone
      healing and bone neogenesis.
AB  - The research reviewed in this paper constitutes a series of investigations
      intended to develop and evaluate a new membrane technique, which provides
      improved conditions for osteogenesis during healing of bone defects and
      restitution of earlier existing bone. The technique has also been shown to aid in
      bone grafting as well as having the capacity to create new bone for
      reconstructive purposes. According to this methodology, membranes are utilized to
      create a space in the tissue in which osteogenesis can occur relatively
      unimpeded. The paper provides a review of our initial animal experimental work as
      well as some clinical studies with special emphasis on membrane use in
      conjunction with dental implants. Possible mechanisms behind the efficacy of the
      membrane technique are reviewed, and future perspectives of development are also
      discussed. The osteopromotive membrane technique represents a principally new and
      major advance in bone biology and reconstructive skeletal surgery. Based on the
      results obtained by us and by others, the technique is presently utilized
      clinically in some routine applications.

PMID- 8295101
TI  - 1982-1992: a decade of technology development for guided tissue regeneration.
AB  - In the last decade guided tissue regeneration (GTR) therapy has evolved in both
      surgical technique and membrane technology. Given new applications and membrane
      materials, not only must new surgical techniques be critiqued, but membrane
      designs must be critically examined as well. A review of historical membrane
      development suggests that 5 design criteria are essential: 1) tissue integration;
      2) cell-occlusivity; 3) clinical manageability; 4) spacemaking; and 5)
      biocompatibility. These criteria may be applied to select appropriate materials
      and designs for specific GTR applications.

PMID- 8295102
TI  - Treatment of mandibular 3-wall intrabony defects by flap debridement and expanded
      polytetrafluoroethylene barrier membranes. Long-term evaluation of 32 treated
      patients.
AB  - The purpose of this study was to evaluate the healing potential of deep,
      primarily 3-wall intrabony defects which were treated by flap debridement and
      expanded polytetrafluoroethylene (ePTFE) membranes and followed for extended time
      periods. All of the treated defects were in the mandibular arch. Thirty-two
      patients were treated and re-examined at an average of 3 years 5 months. Twenty
      four of these patients had re-entry procedures at the second examination. Sixteen
      of these patients were examined a third time at an average of 4 years 3 months.
      The patients were evaluated for changes in probing depth (PD), clinical
      attachment level (CAL), recession, changes in crestal resorption, and defect bone
      fill. The paired t-test for related samples was used to test for differences
      between examinations. Between Exams 1 and 2 there was a statistically significant
      reduction of pocket depth (3.8 mm), gain in clinical attachment level (4.2 mm),
      and an increase in recession (-1.2 mm). For the 24 patients who had re-entry
      procedures there was an average defect fill of 4.3 mm (P < 0.0001) and 0.33 mm of
      crestal resorption (P < 0.0001). The 16 patients who were examined 3 times
      sustained decreases in PD, gains in CAL, and recession recorded at the second
      examination. These changes were statistically significant at Exam 3. The results
      of this study demonstrate that deep, 3-wall intrabony defects treated by
      debridement and ePTFE barrier membranes will have significant decreases in PD,
      gains in CAL, recession, decreases in crestal resorption, and gains in bone
      fill.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295103
TI  - Guided tissue regeneration and bone grafts in the treatment of furcation defects.
AB  - The present study evaluated the effects of guided tissue regeneration (GTR), with
      and without demineralized freeze-dried cortical bone grafts, in the treatment of
      furcation defects in 4 female beagle dogs with naturally occurring periodontal
      disease. The root surfaces were thoroughly debrided. Four weeks later, full
      thickness facial and lingual mucoperiosteal flaps were reflected using inverse
      bevel incisions on both sides of the mandible involving the 2nd, 3rd, and 4th
      premolar, and the 1st molar teeth. Following debridement, notches were placed on
      the roots at the level of supporting bone. Test quadrants were randomly selected
      and furcations were filled with reconstituted, demineralized, freeze-dried human
      cortical bone grafts. Following bone grafting, all defects were covered with an
      expanded polytetrafluoroethylene (ePTFE) membrane, which was sutured with 4-0
      sutures. Afterward, interproximal sutures were placed through the flaps, assuring
      the flaps covered the membranes completely. The contralateral side, serving as
      control, was treated by debridement only and application of ePTFE membrane. All
      membranes were removed 6 weeks after surgery. Dogs were sacrificed at 4 months
      after surgery. Both mesio-distal and bucco-lingual histologic sections were
      evaluated by descriptive histology. Linear measurements and surface area
      determination of the furcal tissues were carried out using the microscope
      attached to a digitizer. Twelve to 20 nonserial sections were made of the mid
      buccal aspects of each root of each treated tooth. Half of these sections were
      stained with Harris' hematoxylin and eosin (H&E) and the other half stained with
      Mallory's trichrome stain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295104
TI  - Guided tissue regeneration using calcium phosphate implants together with 4
      different membranes. A study on furcations in dogs.
AB  - Four different membranes were used in conjunction with porous calcium phosphate
      granules to treat grade II furcations in lower molars of 6 dogs. Six months later
      block sections were used to measure the amount of regeneration and inflammation.
      The 4 membranes (polycarbonate, silicone rubber, polytetrafluoroethylene, and
      polycaprolactone) all gave similar improvements in bone fill ranging from 1.74 +/
      0.44 mm to 2.02 +/- 0.38 mm while control areas had only 0.34 +/- 0.12 mm. The
      amount of new attachment ranged from 2.32 +/- 0.62 mm to 2.58 +/- 0.62 mm for the
      membranes and was 0.26 +/- 0.11 mm for controls. There were increased numbers of
      chronic inflammatory cells seen with the polycarbonate and polycaprolactone group
      compared to controls and the other 2 membranes.

PMID- 8295105
TI  - Guided tissue regeneration using bioresorbable and non-resorbable devices:
      initial healing and long-term results.
AB  - Studies on periodontal wound healing have resulted in the development of the
      treatment modality known as "guided tissue regeneration" (GTR) based on a
      principle of guiding the proliferation of the various periodontal tissue
      components during healing following periodontal surgery. The first report of a
      human tooth treated according to the principle of GTR was presented 10 years ago
      by Nyman et al. Since then numerous clinical studies and animal experiments have
      been performed bringing the concept of GTR to a clinical reality. We also know
      that the results obtained through GTR therapy can be maintained on a long-term
      basis. The first generation of GTR devices has been non-resorbable, which calls
      for a second surgical procedure. This is avoided when bioresorbable devices
      become available. This paper suggests some demands regarding safety and efficacy
      criteria for both non-resorbable and bioresorbable devices. Results from recent
      animal experiments and clinical studies following the use of a bioresorbable
      device in GTR therapy are presented.

PMID- 8295106
TI  - The role of infection and anti-infection treatment in regenerative therapy.
AB  - Infection associated with regenerative therapy is becoming an increasingly
      important consideration as the frequency and numbers of regenerative procedures
      increase. Specific recommendations for antimicrobial treatment associated with
      membranes, grafts, and implants are presented in the context of establishing
      general principles of infection management.

PMID- 8295107
TI  - Isolation of periodontal species after guided tissue regeneration.
AB  - One advanced localized periodontal lesion in each of 10 patients was treated
      using the guided tissue regeneration procedure. Six weeks after placement of
      expanded polytetrafluoroethylene (ePTFE) membranes, microbial samples were taken
      from each treated site and the membranes were removed. Six weeks later the cases
      were re-evaluated. They had all healed successfully with varying amounts of gain
      of clinical attachment. Gram-negative, anaerobic rods were found in all samples
      and made up 31% of all organisms cultivated. In 1 patient, Porphyromonas
      gingivalis was found in a proportion of 17.5%. Six of the other 9 patients
      harbored Prevotella intermedia (mean proportion 21.3%) and 6 Prevotella
      melaninogenica (6.8%). Fusobacterium and Capnocytophaga were also frequently
      found. The results demonstrate that ePTFE membranes are frequently colonized by
      periodontal microorganisms. The importance of bacterial colonization on clinical
      success is presently not known. Further studies are needed to determine the
      effect of the presence or absence of putative pathogens during guided tissue
      regeneration.

PMID- 8295108
TI  - The management of peri-implant breakdown around functioning osseointegrated
      dental implants.
AB  - Peri-implant tissue breakdown can be the result of microbial action as well as of
      biomechanical and occlusal overload. The long-term goal of the treatment of peri
      implant breakdown is to arrest the progression of the disease and to achieve a
      maintainable site for the patient. Peri-implant bony defects around functioning
      implants can be treated with either non-surgical or surgical (resective or
      regenerative) techniques. Bone regeneration is possible in selected peri-implant
      bony defects of functioning implants if appropriate surgical techniques are
      utilized and the etiologic cause is eradicated.

PMID- 8295109
TI  - Guided tissue regeneration in mucogingival surgery.
AB  - The use of expanded polytetrafluoroethylene (ePTFE) membranes in the treatment of
      mucogingival problems such as gingival recession, has been recently described.
      The major issues raised dealt with creating and maintaining space under the
      membrane and designing a flap that could be coronally positioned and at the same
      time capable of maintaining a good blood supply. The authors proposed the use of
      a trapezoidal flap and some technical space-making solutions, such as the use of
      a suturing technique and different metal structures to support the membranes.

PMID- 8295110
TI  - A gender identity interview for children.
AB  - A 12-item gender identity interview schedule was administered to 85 children
      referred for concerns regarding their gender identity development and 98 clinical
      and normal control children. Factor analysis identified two factors, which were
      labeled Affective Gender Confusion and Cognitive Gender Confusion. The gender
      referred group gave significantly more deviant responses than did the controls on
      both factors. Results were discussed with regard to several diagnostic and
      assessment issues pertaining to children with gender identity disorder.

PMID- 8295111
TI  - A longitudinal analysis of burnout in the health care setting: the role of
      personal dispositions.
AB  - Burnout is frequently interpreted as a situationally induced stress reaction.
      However, the long-term stability of burnout scores and their correlations with
      subjective well-being measures suggest that burnout may also reflect enduring
      qualities of the individual. To assess the contribution of personality to the
      experience of burnout, an exploratory longitudinal study was done. At Time 1, 36
      occupational therapists (32 women, 4 men) from two hospitals completed the
      Maslach Burnout Inventory (MBI; Maslach, 1982) and the NEO Personality Inventory
      (NEO-PI; Costa & McCrae, 1985; a measure of the five-factor model of
      personality). At Time 2, the MBI was again given along with the Work Environment
      Scale (Moos, 1981) to 29 of the original therapists. Moderately strong
      correlations were found between burnout scores and measures of the five factors
      both concurrently and longitudinally. Even when situational variables were
      controlled, personality continued to account for a significant portion of the
      variance in burnout scores. The implications of these findings are discussed.

PMID- 8295112
TI  - Variants of the MMPI 2-7-8 code type: schizotypal correlates of high point 2, 7,
      or 8.
AB  - Our study sought to evaluate whether examination of the high-point scale among
      subjects with a 2-7-8 parent configuration on the MMPI could assist in the
      identification of individuals with schizotypal features. Additionally, this study
      compared male 2-7-8 subjects to female 2-7-8 subjects to determine whether gender
      mediates endorsement of items associated with these features. Subjects (N = 106)
      who produced a 2-7-8 parent profile were subdivided according to high point (2,
      7, or 8), and the three subgroups were subsequently compared on other self-report
      measures associated with schizotypal attributes. Subgroup comparisons revealed
      that the High 8 and High 2 groups produced a pattern of responding consistent
      with schizotypal characteristics. In contrast, the at-risk status of the High 7
      group appears doubtful. Comparisons based on gender generally revealed no
      differences among female and male 2-7-8 subjects.

PMID- 8295113
TI  - Measurement of hostility, anger, and depression in depressed and nondepressed
      subjects.
AB  - This study examined the relationship between hostility and depression in
      depressed and nondepressed subjects as well as the reliability and validity of
      several measures of anger, hostility and depression. Sixty-nine subjects were
      evaluated for depression using the Hamilton Rating Scale for Depression (HRSD;
      Hamilton, 1960). These subjects were then administered the Beck Depression
      Inventory (BDI; Beck, Ward, Mendelson, Mock, & Ergaugh, 1961), Buss-Durkee
      Hostility Inventory (BDHI; Buss & Durkee, 1957), Hostility and Direction of
      Hostility Questionnaire (HDHQ; Foulds, Caine, & Creasy, 1960) and the State-Trait
      Anger Scale (STAS; Spielberger, Jacobs, Russell, & Crane, 1983). Results showed
      the BDI, STAS-TRAIT, HDHQ, and BDHI to have good temporal stability. Support was
      found for the convergent validity of all measures of depression, hostility, and
      anger. Limited discriminant validity was found between measures of anger and
      hostility and measures of depression. This latter finding was interpreted as
      lending support for the relationship between hostility and depression rather than
      as an indication of limited construct validity for the measures.
      Intercorrelations among hostility, anger, and depression scales offer some
      support for the hypothesis that depression is linked most strongly with
      attitudinal versus motoric forms of hostility. However, normative data suggests
      that both forms of hostility increase with severity of depression. Clinical
      implications and directions for further research are discussed.

PMID- 8295114
TI  - A longitudinal study of changes in children's thought content in response to
      frustration on the Children's Picture-Frustration Study.
AB  - A longitudinal design examined changes in the 11 response types on the Children's
      Form of the Picture-Frustration (P-F) Study. Eighty-six children were retested on
      the instrument after a 5-year interim. Children showed changes reflecting an
      increase in verbal aggression and an increase in making amends for wrongdoing.
      They showed decreases in unfocused emotional outbursts and apologies. The
      findings add to the literature on children's emotional development of aggression
      and guilt and on the validity of the instrument.

PMID- 8295115
TI  - Psychometric properties of a cognitive measure of personality disorders.
AB  - This study evaluated the internal consistency, 1-month test-retest reliability,
      and validity of a cognitive measure of personality disorders, the Belief
      Questionnaire (BQ; Beck, 1990). A large, nonclinical sample of college
      undergraduates completed the BQ, the MMPI-Personality Disorder scales (MMPI-PD;
      Morey, Waugh, & Blashfield, 1985), and the Personality Diagnostic Questionnaire
      Revised (PDQ-R; Hyler & Rieder, 1987) at two times separated by 1 month. Results
      indicated high internal consistency and test-retest reliability for the BQ
      subscales. Validity results, however, were not so strong. The BQ scales were
      highly positively intercorrelated, and only moderate correspondence between BQ
      scores and corresponding scores from the MMPI-PD and PDQ-R was found.

PMID- 8295116
TI  - Incremental validity of the MMPI-2 Content Scales in the assessment of
      personality and psychopathology by self-report.
AB  - The incremental contribution of the MMPI-2 Content Scales to the prediction of
      scores on self-report measures of personality and psychopathology was
      investigated. The MMPI-2, Beck Depression Inventory, State-Trait Personality
      Inventory, and Symptom Checklist-90-Revised were administered to 596 subjects:
      339 women and 257 men. Zero-order correlational analyses indicated that both
      clinical and Content Scales correlated with each of the criterion measures. In
      all but one case, an MMPI-2 Content Scale was found to have the highest
      correlation with the extratest variables. Combined hierarchical, stepwise
      regression analyses demonstrated that the MMPI-2 Content Scales possess
      incremental validity vis-a-vis the clinical scales for both genders in relation
      to all of the criterion measures. Additional analyses indicated that the MMPI-2
      clinical scales also possess incremental validity vis-a-vis the Content Scales.
      However, the incremental contribution of the clinical scales was of lesser
      magnitude. Implications of these findings for test interpretation and future
      research with the MMPI-2 are discussed.

PMID- 8295117
TI  - Ironic processes in the mental control of mood and mood-related thought.
AB  - The mental control of mood and mood-related thought was investigated. In
      Experiment 1, Ss reminiscing about a happy or sad event were asked to make their
      mood positive, were given no instructions, or were asked to make their mood
      negative. Ss attempting mood control without an imposed cognitive load were
      successful, whereas those who attempted control while rehearsing a 9-digit number
      not only failed to control their moods but also showed self-reported mood change
      opposite the mood they intended to create. In Experiment 2, Ss attempting to
      control mood-related thoughts under cognitive load showed increased accessibility
      of those thoughts contrary to the direction of intended control in a Stroop-type
      color-naming task.

PMID- 8295118
TI  - There's more to self-esteem than whether it is high or low: the importance of
      stability of self-esteem.
AB  - Study 1 examined the extent to which stability and level of self-esteem predicted
      cognitive and emotional reactions to interpersonal feedback. Among high self
      esteem individuals, instability was associated with acceptance and positive
      emotions following positive feedback but to rejection and defensiveness following
      negative feedback. Among low self-esteem individuals, instability was unrelated
      to reactions to positive feedback but was related to less defensiveness and
      greater acceptance of negative feedback. Study 2 examined the extent to which
      variability and importance of specific self-evaluations were associated with
      instability of global self-esteem. Discussion focused on the roles of level and
      stability of self-esteem in reactions to evaluations and on the nature of self
      esteem instability.

PMID- 8295119
TI  - Personality and self-efficacy as predictors of coping with abortion.
AB  - The present study explored the relationships among dispositional optimism, self
      esteem, chronic perceptions of control, depression, and self-efficacy in
      predicting psychological adjustment among women undergoing an abortion. Self
      efficacy was found to be a strong, proximal predictor of adjustment, both
      immediately after the abortion and 3 weeks later. Optimism, perceptions of
      personal control, and high self-esteem were all related to better postabortion
      adjustment (mainly through the mediator of increased self-efficacy for coping).
      In addition, the effects of these three personality variables were found to
      overlap considerably. Finally, preabortion depression had both direct and
      indirect (through self-efficacy) effects on adjustment. These effects did not
      overlap completely with the effects attributable to personality.

PMID- 8295120
TI  - Response expectancies and interpretations as determinants of hypnotic responding.
AB  - Ss rated the extent to which they expected to respond to each of the suggestions
      on a hypnotizability scale both before and after the administration of the
      preliminary hypnotic induction procedure. After the induction, Ss also rated the
      extent to which they planned to respond actively and passively to each
      suggestion. Contrary to strong versions of response-expectancy theory, the extent
      to which Ss planned to adopt an active interpretation predicted behavioral and
      subjective indexes of hypnotizability even after controlling for the effects of
      postinduction expectations. In addition, an active interpretation significantly
      predicted response to suggestion for which Ss held weak and uncertain
      expectations. The relationship between expectation and hypnotizability was found
      to be fan-shaped rather than linear. Implications are discussed.

PMID- 8295121
TI  - Social support in pregnancy: psychosocial correlates of birth outcomes and
      postpartum depression.
AB  - This prospective study examined the effects of prenatal social support on
      maternal and infant health and well-being in a sample of low-income pregnant
      women (N = 129). Three aspects of support (amount received, quality of support
      received, and network resources) and four outcomes (birth weight, Apgar scores,
      labor progress, and postpartum depression) were studied. Results indicated that
      women who received more support had better labor progress and babies with higher
      Apgar scores. Women with higher quality support had babies with higher Apgar
      scores and experienced less postpartum depression. Also, women with larger
      networks had babies of higher birth weight. Further analyses indicated that the
      outcomes as a whole were more consistently predicted by instrumental rather than
      emotional forms of support. Finally, although there was some evidence for stress
      buffering effects of support, the overall findings were more consistent with a
      main effect model.

PMID- 8295122
TI  - Emotional trade-offs of becoming a parent: how social roles influence self
      discrepancy effects.
AB  - Why do some people suffer from becoming a parent, whereas others do not? New
      parents' actual selves were related to their own hopes for themselves (ideal
      self) and to their spouse's sense of their responsibilities (ought self).
      Prebirth actual-ideal discrepancies predicted increased sadness or dejection
      after birth (especially for couples in longer marriages), whereas prebirth actual
      ought discrepancies predicted decreased nervousness or agitation after birth
      (especially for mothers and couples with a less "easy" child). Becoming a parent
      introduces new demands that both interfere with attaining one's own hopes
      (increasing dejection in parents high in ideal [own] discrepancy) and shift
      attention to the new parenting role (decreasing agitation in parents high in
      ought [spouse] discrepancy).

PMID- 8295123
TI  - Effects of uncontrollability on subsequent decision making: testing the cognitive
      exhaustion hypothesis.
AB  - The cognitive exhaustion model of helplessness--predicting withdrawal from
      constructive effortful processing after uncontrollability--was applied to
      decision making. After unsolvable problems (or no preexposure), Ss requested
      information from a matrix with 5 alternatives (films) x 10 attributes and then
      chose the best film. Films in a set were either similar (difficult decision) or
      dissimilar (easy decision) in attractiveness. As predicted, Ss with an
      uncontrollable preexposure spent less time on predecisional information search,
      disregarded their own importance criteria when asking for information, and had
      attention highly focused on a selected option for the easy decision condition but
      diffused across options for the difficult decision condition. The implications of
      these findings for understanding cognitive mechanisms of learned helplessness and
      depression are discussed.

PMID- 8295124
TI  - Calcaneal donor bone grafts.
AB  - Autogenous bone grafting is an important part of many foot and ankle surgical
      procedures. Although alternative bone graft materials such as allogeneic bone are
      available, autogenous bone continues to be the material of choice for many
      procedures. The calcaneus provides a source of small amounts of autogenous
      corticocancellous or cancellous bone. The author describes the surgical technique
      for procurement of calcaneal bone grafts. Twenty-five cases are reviewed. The
      morbidity associated with procuring calcaneal bone grafts is favorably compared
      with that associated with procuring bone from other donor sites.

PMID- 8295125
TI  - Orthosorb resorption evaluation using MRI and histologic analysis.
AB  - Resorbable bone fixation devices may be used in various surgical procedures for
      internal fixation in place of traditional metallic devices. Currently, there is
      no radiographic technique for tracing the postsurgical location and resorption of
      these devices. This study was undertaken to ascertain whether magnetic resonance
      imaging is a suitable tool for performing such evaluations. Using an animal
      model, the authors investigated the correlation over time between the magnetic
      resonance image of a surgically implanted pin and its histologically verified
      location and state.

PMID- 8295126
TI  - MRI evaluation of Orthosorb pin insertion for surgical treatment of hallux
      abducto valgus.
AB  - This preliminary study considers the advantage of magnetic resonance imaging over
      plain film radiography in assessing pin resorption and bone marrow regeneration
      over a 6-month period. The Orthosorb pin was used to fixate an Austin osteotomy
      in a patient and was followed with serial magnetic resonance imaging at scheduled
      intervals. This study expands on the preceding study in this issue of the
      Journal, which was carried out in the rat model.

PMID- 8295127
TI  - Tibialis posterior tendon associated with hallux abducto valgus. A preliminary
      study.
AB  - The etiology of hallux abducto valgus has been the topic of much study. The
      authors of this study have attempted to investigate an association of anomalous
      insertions of the tibialis posterior tendon and their relationship to hallux
      abducto valgus. The authors present evidence that such anomalous insertions are
      normal, but may contribute to the development of the deformity because of
      variations in those insertions. A biomechanical model for that contribution is
      proposed.

PMID- 8295128
TI  - Renal osteodystrophy with pedal involvement.

PMID- 8295129
TI  - Medial fracture dislocation of hallucal interphalangeal joint. A case report.
AB  - A case of medical fracture dislocation of the hallucal interphalangeal joint is
      presented. The patient did not recall the specific mechanism that caused this
      injury. However, this type of injury would have to entail a substantial lateral
      to-medial force at the distal phalanx. The authors' review of the literature did
      not reveal a similar case involving a medial dislocation of the distal phalanx.
      This transverse plane pathology was treated with closed reduction because of a
      lack of sesamoid or volar plant involvement in the joint.

PMID- 8295130
TI  - Peripheral neuropathy associated with Waldenstrom's macroglobulinemia.

PMID- 8295131
TI  - Introducing MEDWatch. A new approach to reporting medication and device adverse
      effects and product problems.

PMID- 8295132
TI  - Subungual pigmented Bowen's disease in a nineteen-year-old black female.

PMID- 8295133
TI  - Council on podiatric medical education. Seventy-fourth annual report, 1993.

PMID- 8295134
TI  - Sock durability.

PMID- 8295135
TI  - Health care reform: more myth than reality.

PMID- 8295136
TI  - Analytical data of March 1993 blast victims--the KEM Hospital experience.
AB  - On 13th March 1993 consequent to a series of explosions in the city a large
      number of casualties were attended to at this hospital. A total of 248 patients
      were treated for various injuries which included 85 minor and 34 major
      operations. Seventy-nine patients were brought in "dead on arrival". There were
      12 deaths after admission out of which 6 patients died after surgery. The cause
      of death was hemorrhagic shock in 5 patients, burns in 2, severe head injury in
      2, and shock lung in 3 patients.

PMID- 8295137
TI  - Occasional head of flexor pollicis longus muscle: a study of its morphology and
      clinical significance.
AB  - A cadaveric dissection study of 54 upper extremities to determine the incidence
      of occurrence, morphology and relations of the occasional head of the flexor
      pollicis longus muscle is presented. The occasional head of the flexor pollicis
      longus muscle was found to be present more frequently (66.66%) than absent. It
      mainly arose from the medical epicondyle of the humerus (55.55%) and the medial
      border of the coronoid process of the ulna (16.66%). It was found to be in close
      association with the median nerve (anteriorly) and the anterior interosseous
      nerve (posteriorly). The clinical implications of these findings are discussed
      viz. entrapment neuropathies of the median and anterior interosseous nerves,
      cicatricial contraction of the occasional head leading to flexion deformity of
      the thumb and the likely necessity to lengthen/release the occasional head in
      spastic paralysis of the flexor pollicis longus muscle.

PMID- 8295138
TI  - Disaster management--are we ready?

PMID- 8295139
TI  - Vesical fistulae--an experience from a developing country.
AB  - This study analyses patients with vesical fistulae presenting at a teaching,
      referral hospital over the last ten years. There were 62 cases of vesical
      fistulae of which 60 were obstetric in origin (44 home and 16 hospital
      deliveries) and 2 were following gynaecological surgery. Of the hospital
      deliveries which culminated in fistula formation, 8 were vaginal and 7 forceps
      deliveries. In one patient, lower segment caesarean section was carried out.
      After a thorough urological work-up, patients were subjected to standard
      technique of layered closure (61 by vaginal approach and one by abdominal).
      Repair was successful in 53 (87.09%) patients. Of the 9 failures, 4 were repeat
      repairs.

PMID- 8295140
TI  - Quantitation of microbicidal activity of mononuclear phagocytes: an in vitro
      technique.
AB  - An in vitro assay technique was set up to determine the phagocytic and
      microbicidal activity of a monocyte-macrophage cell line using Candida species as
      test organisms. The norms were determined for the activity of peritoneal
      macrophages of rats (24.69 +/- 2.6% phagocytosis and 35.4 +/- 5.22% ICK) and
      human (27.89 +/- 3.63% phagocytosis and 50.91 +/- 6.3% ICK). The assay technique
      was used to test the degree of activation of macrophages induced by
      metronidazole, Tinospora cordifolia and Asparaqus racemousus and to compare their
      effects with a standard immunomodulator muramyl-dipeptide. All the three test
      agents increased the phagocytic and killing capacity of macrophages in a dose
      dependent manner upto a certain dose, beyond which either these activities were
      found to have plateaued or decreased. The optimal doses for MDP, Metronidazole,
      Asparagus racemosus and Tinospora cordifolia were found to be 100 micrograms, 300
      mg/kg, 200 mg/kg and 100 mg/kg respectively. Patients with cirrhosis were
      screened for defects in monocyte function. The depressed monocyte function (20.58
      +/- 5% phago and 41.24 +/- 12.19% ICK; P < 0.05) was observed indicating a
      compromised host defense. The utility of this candidicidal assay in experimental
      and clinical studies is discussed.

PMID- 8295141
TI  - Hypotensive anaesthesia for spine surgery--nitroglycerin vs halothane.
AB  - Thirty patients (ASA I or II) requiring spine surgery under general anesthesia
      were studied. To induce hypotension, halothane 0.5 to 2.5% (n = 15) or
      nitroglycerin infusion (1-2 micrograms/kg/min) (n = 15) was used. The parameters
      studied were blood pressure, blood loss, operating time and recovery score. The
      systolic blood pressure was maintained between 80-100 mmHg during surgery in both
      the groups. The blood loss with nitroglycerin was significantly less (202 +/- 114
      ml) than halothane group (602 +/- 312 ml). All the patients were alert at the end
      of surgery in the nitroglycerin group (recovery score 9.8 +/- 0.76) as against
      the halothane group (7.98 +/- 0.9 p < 0.01). Tachycardia or tachyphylaxis was not
      observed with nitroglycerin. This study suggests that continuous intravenous
      infusion of nitroglycerin is effective and safe in reducing blood loss and
      operating time during spine surgery.

PMID- 8295142
TI  - Enhancement of colposcopic image by sulphosalicylic acid.
AB  - Acetic acid is used conventionally for enhancement of the colposcopic image. We
      used sulphosalicylic acid instead of acetic acid in 50 normal cases. The normal
      appearance was enhanced in all cases. The image was also enhanced in 70% cases of
      cervical intraepithelial neoplasia and 90% cases of cervical condyloma
      accuminata. The image was not inferior to that with acetic acid in any of the
      cases.

PMID- 8295144
TI  - Oesophageal manometry: an overview.

PMID- 8295143
TI  - MBBS examinations--are we asking the right questions?

PMID- 8295145
TI  - Congenital epulis.
AB  - A tumor was found to be arising from the right maxillary alveolar margin of a
      newborn baby. No other congenital abnormality was detected. Following excision
      and histopathological examination, diagnosis of benign congenital granular cell
      epulis was made. The post-operative course was uneventful.

PMID- 8295146
TI  - Tuberculosis of the renal artery.
AB  - A young female who underwent nephrectomy for renovascular hypertension was
      diagnosed on histology to have tuberculosis of the renal artery. This was an
      isolated finding as there was no tuberculous infection elsewhere including
      tissues in the vicinity of the vessels. A survey of literature did not yield any
      reports of tuberculous renal arteritis, making this the first such case.

PMID- 8295147
TI  - Bilateral otogenic cerebellar abscesses.
AB  - An unusual presentation of bilateral otogenic cerebellar abscesses observed in
      two of our patients is reported. Both gave a history of otorrhoea, fever,
      headache, vomiting and had bilateral cerebellar signs and conductive hearing
      loss. The abscesses were detected on computerised tomography. X-rays revealed
      bilateral mastoiditis. The therapy followed was excision of abscesses,
      mastoidectomy and antibiotic therapy.

PMID- 8295148
TI  - Splenic cyst.
AB  - An 11 year old boy presenting with cystic lump in left hypochondrium was
      diagnosed to have splenic cyst and treated successfully by splenectomy. Large,
      infected cyst involving hilum was the indication.

PMID- 8295149
TI  - Gastric lipoma presenting as obstruction and hematemesis.
AB  - A rare case of gastric lipoma presented to us with hematemesis and symptoms of
      obstruction. On oesophagoduodenoscopy, a mass projecting in the lumen of stomach
      was found. Barium meal examination revealed a mass in the antral region
      suggestive of malignancy. The diagnosis of lipoma was suspected only after
      exploration. It was confirmed following incision through the serosa. The lipoma
      was enucleated without any damage to mucosa.

PMID- 8295150
TI  - Cladosporium bantianum (trichoides) infection of the brain.
AB  - A 32 yr old male patient with history of convulsion and bitemporal headache was
      diagnosed as suffering from tuberculoma based on CT Scan. He worsened after anti
      tuberculous therapy. The patient underwent parieto-occipital craniotomy with
      drainage of abscess. The histopathological examination of brain abscess revealed
      the infection with cladosporium bantianum. The details of this rare case of
      opportunist fungal cerebral lesions in healthy individual are reported.

PMID- 8295151
TI  - The mythology of modern medicine--I. Scienstition.

PMID- 8295152
TI  - Balloon mitral valvotomy: our perspective.

PMID- 8295153
TI  - Analytical data of January 1993 communal riot victims--the KEM Hospital
      experience.
AB  - Bombay experienced a violent outbreak of communal rioting in January 1993. Four
      hundred and thirteen casualties were treated in the KEM hospital from January 7
      to January 15, of which 194 required admission and further management. Twenty
      seven were brought dead on arrival. The large influx of casualties sustained over
      a period of 9 days tended to overwhelm the medical facilities. The data of the
      admitted patients are analyzed to identify the frequency of admissions, cause and
      nature of injuries sustained, management and prognosis of casualties in such a
      catastrophe. An attempt is also made to identify the problems faced during such a
      crisis and a few suggestions made for their solution.

PMID- 8295154
TI  - Marketing of medical care.

PMID- 8295155
TI  - Prolactin response to electroconvulsive shock in anesthetized rats.
AB  - Serum prolactin level (SPL) of anesthetized rats was measured in response to
      electroconvulsive shock (ECS). This measurement served as an indicator of
      dopaminergic and serotonergic activity. Such neurotransmitter activity was
      modulated by pretreatment with cyproheptadine, parachlorophenylalanine (PCPA),
      pimozide, bromocriptine or L-dopa. A statistically significant lowered SPL was
      found in rats given ECS plus antiserotonergic agents, in comparison with animals
      receiving antiserotonergic agent or ECS alone. When ECS was administered to rats
      pretreated with the dopaminergic blocker, pimozide, there was a significant
      decrease in SPL, compared with animals receiving pimozide alone. When the
      dopaminergic system was stimulated by dopamine agonists, there was no elevation
      of SPL in response to ECS. Thus, there may be a balance between serotonergic and
      dopaminergic systems. The agents used in the experiment may upset this balance
      and produce a change in prolactin response to a given ECT stimulus.

PMID- 8295156
TI  - An association between the lysosomal enzyme NAG and urinary free cortisol and
      platelet imipramine binding.
AB  - Urinary levels of the lysosomal enzyme N-acetyl-beta-glucosaminidase (NAG) were
      significantly correlated to levels of 24-hour urinary free cortisol in a group of
      panic disordered patients. In a separate study of healthy controls NAG levels
      showed a trend toward association with platelet imipramine binding density. A
      hypothesis is proposed that NAG levels may be proportional to the density of
      postsynaptic serotonin receptors.

PMID- 8295157
TI  - Telephone assessment of depression severity.
AB  - This report describes the adaptation of three common measures of depression
      severity, the Hamilton Depression Rating Scale, the Structured Clinical Interview
      for DSM-III-R, and selected items of the Symptom Checklist-90 for follow-up
      assessment by telephone. In a sample of 30 patients beginning antidepressant
      treatment, telephone and in-person assessment of current symptom severity
      produced nearly identical results for all three instruments.

PMID- 8295158
TI  - Exactly what does the Hamilton Depression Rating Scale measure?
AB  - The purpose of this study is to evaluate empirical criticism of the psychometric
      properties of the Hamilton Depression Rating Scale (HDRS) by undertaking an
      "internal construct validity" evaluation. Individual symptom responses for the
      HDRS were obtained from 370 patients meeting Research Diagnostic Criteria for
      major depression. A multidimensional normal item response theory (IRT) model was
      used to assess the dimensionality of the HDRS and estimate corresponding item
      parameters which were then expressed as factor loadings and item thresholds. The
      analysis yielded a five-dimensional solution. The first dimension (depressed
      mood, guilt, suicide, work and interests, agitation, psychic anxiety, somatic
      anxiety, and loss of libido) appeared to define global depression severity. These
      results are consistent with other published factor analytic studies and provide
      further justification for thinking that the HDRS total score is a weak index of
      depressive syndrome severity. The findings provide a benchmark by which the
      adequacy of future results may be judged, because the multidimensional IRT model
      does not suffer from the statistical limitations that arise when applying
      traditional factor analytic methods to discrete symptom ratings.

PMID- 8295159
TI  - Functional properties of deoxycorticosterone and spironolactone: molecular
      characterization and effects on sleep-endocrine activity.
AB  - Adrenal steroid hormones are capable of interfering with a variety of behavioral
      phenomena including sleep. The mechanisms appear to involve effects at the cell
      membrane as well as nuclear actions mediated by intracellular mineralo- and
      glucocorticosteroid receptors (MR and GR). We employed the MR agonist
      deoxycorticosterone (DOC) and the MR antagonist spironolactone (SP) to study the
      role of MRs in the regulation of human sleep. We also tested whether the effects
      of DOC upon the sleep EEG and nocturnal hormone secretion (growth hormone and
      cortisol) are compatible with those predicted for its major metabolite tetrahydro
      DOC (THDOC): electrophysiological and animal experiments had suggested that THDOC
      would act as a hypnotic via positive modulation of the GABAA receptor. Because
      neither DOC nor SP affected the sleep EEG substantially, the involvement of MRs
      in the regulation of sleep needs further study. The sleep-endocrine data showed a
      suppressive effect of DOC upon plasma cortisol concentrations and an earlier
      occurrence of nocturnal GH maxima, which can be plausibly explained by GR or
      sigma receptor-mediated effects. Molecular characterization of DOC and SP
      confirmed a relatively strong effect of DOC upon transactivation via MR and no
      effect of SP on the GR-mediated transcription rate. In addition, the possibility
      that a low dose of the mineralocorticoid DOC may serve as a prodrug for the
      potential hypnotic THDOC is not supported by the current data.

PMID- 8295160
TI  - Psychomotor monitoring: a promise being fulfilled?

PMID- 8295161
TI  - Speaking behavior and voice sound characteristics in depressive patients during
      recovery.
AB  - Based on a sample of 30 depressive patients, we have investigated the time course
      of recovery from depression in so far as this time course was assessable through
      changes in psychopathology syndrome scores and through changes in speaking
      behavior and voice sound characteristics. Specifically, our study design provided
      6 repeated assessments over 2 weeks and at a fixed time in the morning each
      Monday, Wednesday and Friday, plus a final assessment at the patients' releases
      from hospital. Thus, we were able to determine the degree to which single
      parameter approaches to speaking behavior and voice sound characteristics reflect
      the individual time course of recovery from depression. In this context, we could
      rely upon a calibration sample with repeated assessments on 192 healthy
      volunteers which yielded all necessary information concerning reproducibility and
      sensitivity of speech parameters. Our analysis revealed several prominent
      features of speaking behavior and voice sound characteristics to be closely
      related to the time course of recovery from depression. In particular, the
      parameters "F0-amplitude", "F0-6db-bandwidth" and "F0-contour" which assess
      important characteristics of a speaker's voice timbre, as well as the parameters
      "energy" and "dynamics" which assess a speaker's mean loudness and the variation
      of loudness over time, displayed consistently high correlations with depression
      syndromes. Moreover, the results of single-case analysis turned out to be in
      remarkable accordance with those of the cross-sectional one: in almost two-thirds
      of patients there existed a significant relationship over time between the global
      depression scores and major speech parameters. As to the remaining one-third of
      patients who did not fit the picture of high correlations between psychopathology
      and speech parameters, we found an overproportionally large number of non
      improvers characterized by irregular patterns of slight improvement with
      subsequent deterioration, or of deterioration followed by slight improvement. In
      other words, one-third of patients displayed time courses of depression whose
      psychopathology is difficult to assess through standard exploration techniques.
      Accordingly, it is not clear whether the observed lack of correlation in these
      patients is due to insufficient data or to an actual discordance between the time
      development of psychopathology and that of speech parameters.

PMID- 8295162
TI  - Abnormal speech articulation, psychomotor retardation, and subcortical
      dysfunction in major depression.
AB  - Psychomotor retardation, characterized by changes in speech, motility and
      cognition, is common in major depression. It is also a cardinal feature of
      subcortical disorders such as Parkinson's disease (PD). Based on this observation
      and other data it has been hypothesized that the retardation of depression is
      related to mesolimbic-nigrostriatal dysfunction. To further test this hypothesis,
      speech articulation in major depression was compared to that in PD, where
      disordered articulation is related to bradykinesia and rigidity caused by
      striatal dopamine depletion. Thirty subjects with major depression were compared
      with 30 patients with PD and 31 normal controls on 3 acoustic measures of
      articulation. Major depression and PD groups had significantly shortened voice
      onset time and decreased second formant transition compared to controls, and
      major depression also had increased spirantization. There were no differences
      between the depression and PD groups on any of the acoustic measures. These
      findings provide indirect support for the hypothesis that nigrostriatal
      dysfunction is related to psychomotor slowing in major depression.

PMID- 8295163
TI  - Coming to terms with stress: effects of stress location in sentence processing.
AB  - The purpose of this research was to determine the role of syllabic stress in
      language processing during the early on-line processing of speech and later in
      the representation of a sentence in memory. Experiment 1 used a syllable
      monitoring task while Experiment 3 used a probe task in which subjects heard a
      sentence and then were asked to determine whether a probe syllable had occurred
      in the sentence. In the monitoring task, stressed syllables were detected more
      rapidly in word-initial position, but unstressed syllables were detected more
      rapidly in word-final position. Stress facilitation in initial syllables was
      strongly related to high relative F0, but not to changes in perceived vowel
      quality as assessed in Experiment 2. This pattern is interpreted as evidence that
      lexical stress is used on-line to guide lexical access and/or lexical
      segmentation. The probe task of Experiment 3 showed stress facilitation in both
      positions, indicating that stress is independently retained in the postperceptual
      representation of a sentence.

PMID- 8295164
TI  - Radiosensitization of human lung fibroblasts by chemical that decrease ATP
      levels.
AB  - Radiosensitization by lactate, pyruvate, nalidixic acid and novobiocin was
      studied in exponentially growing SH-18L human lung fibroblasts. All the chemicals
      had a slight radiosensitizing effect at a low concentration and a definite effect
      at a higher one. Decreases in the D0 and/or Dq values were present in each dose
      survival curve. Fibroblasts incubated with the low concentration of each chemical
      for 24 hrs after X irradiation showed no reduction in intracellular ATP content,
      whereas, the higher concentration produced a significant decrease. These
      observations suggest that the decrease in the ATP content may be involved in the
      radiosensitization of human fibroblasts at high concentrations of these
      chemicals. In contrast, radiosensitization at a low concentration is not
      explained by a relationship to ATP content. Different mechanisms may be involved
      in radiosensitization at low and high concentrations of these chemicals.

PMID- 8295165
TI  - Disturbance of neuronal migration in mouse cerebral cortex by low-dose gamma
      radiation.
AB  - We show that neuronal migration is disturbed by low-dose gamma-radiation of 0.24
      Gy in the developing cerebral cortex of mice and suggest that neuronal
      progenitors in the S phase of mitosis are more sensitive than those in the G1/G0
      phase. To pulse-label the fetal cells pregnant Slc:ICR mice were injected with
      bromodeoxyuridine (BrdU) at 10.00 pm on day 16 of pregnancy or at 9.30 am on day
      17. The mice then were exposed to 0.24 Gy gamma- or sham-irradiation at 10.00 am
      on day 17 of pregnancy. At the time of exposure cells labeled on day 16 were
      regarded as having completed mitosis, and those labeled on day 17 as being in the
      S phase. Cell death in the fetal ventricular zone after exposure was negligible.
      Dams were allowed to give birth and rear their litters. Brain samples obtained
      from offspring on the 2nd day after birth and at 6 weeks of age were used for the
      immunohistochemical examination of BrdU-labeled cells. Labeled cells remaining in
      the ventricular zone were significantly more numerous in irradiated animals than
      in sham-exposed ones on the 2nd day after birth, in mice treated prenatally with
      BrdU on day 17 of pregnancy; whereas, mice treated with BrdU on day 16 showed no
      statistically significant difference. At 6 weeks of age, in both groups most of
      the labeled cells were present in layers II-III of the SmI cerebral cortex. But,
      in the irradiated animals the labeled cells in these layers were significantly
      fewer and those in layers IV-VI more numerous than in the sham-exposed mice in
      both group treated with BrdU on day 16 or 17.

PMID- 8295166
TI  - Root-uptake of radioiodine by rice plants.
AB  - Root-uptake of iodine by rice plants from two different soil types was studied
      using an 125I tracer. At harvest, the 125I concentration was lowest in brown rice
      (hulled rice) followed by the rachis, stem and leaves. The transfer factors of
      iodine for brown rice grown on Andosol and Gray lowland soil (fine texture)
      respectively were 0.007 and 0.002. The ratio of the radioiodine concentrations
      between flag leaf (first leaf blade) and brown rice was about 400. Transfer
      factors in plants grown on Andosol were higher than those grown on Gray lowland
      soil. This may be related to the high 125I concentration in the Andosol soil
      solutions, particularly after the flowering period. The adsorption and desorption
      of iodine in the soil was effected by flooding with water and also by the
      cultivation of rice plants. The radioiodine concentration in the soil solutions
      first increased in the upper soil layer than in the lower layer. The desorption
      pattern of iodine was influenced by the soil types.

PMID- 8295167
TI  - Energy deposition in structural parts of DNA by monoenergetic electrons.
AB  - The Monte Carlo simulation of energy deposition in structural parts of DNA based
      on "Structural Model" is described. This model takes under consideration space
      positions of atoms in B-form of DNA and clearly defines sensitive volumes of each
      nucleotide (phosphodiester bonds, sugar, base, hydrogen bonds). ETRACK code
      producing the positions of energy deposition events in water vapor medium is used
      for simulation of electron track structure. The electron production points are
      chosen randomly within the sphere containing cell nucleus. DNA segments are
      randomly distributed in cell nucleus. Each energy deposition point is tested if
      it occurs in any element of any DNA part. The highest probability of energy
      deposition is found for phosphodiester bonds area, whereas the lowest for
      deoxyribose area. Electrons of initial energies from 5 keV to 10 keV have higher
      probability of energy deposition in structural part in comparison with lower and
      higher energy electrons.

PMID- 8295168
TI  - Effects of dose rate and energy level on fission neutron (252Cf) tumorigenesis in
      B6C3F1 mice.
AB  - The effects of the dose rate and the energy of fission neutrons using an iron
      block on tumorigenesis in B6C3F1 mice were examined. Six-week-old female animals
      were divided into 4 groups and exposes to 252Cf neutron irradiation at dose rates
      of 0.05 cGy/min, with (Group 1) or without (Group 2) filtering through a 10 cm
      thick iron block, 0.8 cGy/min (Group 3) or 0 (Group 4 controls). Total neutron
      exposure was 50 cGy in each of groups 1-3 and total irradiation dose was 56, 75
      and 75 cGy in Groups 1-3, respectively. Total tumor incidences or multiplicity
      were significantly higher in Group 3 than in Group 1. A similar tendency was
      observed as compared to Group 2, ovarian and Harderian gland tumors being mainly
      affected and adrenal tumors were significantly higher in Group 2 than in Group 1.
      The results indicated a clear increase in tumorigenesis with the higher dose rate
      and no filtering influence of iron was evident, despite the drop in neutron
      energy level.

PMID- 8295169
TI  - The carcinogenic effect of solar activity with different intensities on embryos.
AB  - The carcinogenic effects of solar activity with different intensities on embryos
      were studied epidemiologically. The study reveals that receiving a moderate
      amount of low level cosmic radiation at embryonic stage may reduce cancer
      occurrence later. This paper analyses and discusses the mechanisms of this
      hormetic effect.

PMID- 8295170
TI  - On the epidemiology of polymyalgia rheumatica and temporal arteritis.

PMID- 8295171
TI  - Neuropsychiatric lupus: a case for guarded optimism.

PMID- 8295172
TI  - Eosinophilia-myalgia syndrome: morbidity and mortality.

PMID- 8295173
TI  - Cytokine production by helper T cell populations from the synovial fluid and
      blood in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Our study was undertaken to determine the phenotypic changes and
      cytokine production from the synovial fluid (SF) and blood of patients with
      rheumatoid arthritis (RA). METHODS: Blood and SF purified T cells were stained
      with monoclonal antibodies using standard, indirect immunofluorescence technique
      for the determination of T cell receptor (TcR) TcR alpha beta and TcR gamma delta
      antigen expressions, CD25, CD38, CD71, HLA-DR activation antigens, and for
      percentage distribution of CD4+CD29+ and CD4+CD45RA+ subsets. The production of
      interleukin 2 (IL-2), IL-4 and IL-6 by various T cell compartments was determined
      by the bioassay or enzyme linked immunosorbent assay methods. RESULTS: Highly
      elevated percentage of CD3+TcR gamma delta and CD4+CD29+ T cell subsets were
      detected in SF and blood of RA. The CD4+CD29+ T cell subsets produced elevated
      levels of IL-4 and IL-6 but deficient levels of IL-2. IL-6 cytokine induced
      CD4+CD29+ subsets were found to provide effective helper function to B cells in
      IgG and IgM synthesis. CONCLUSION: The IL-6 production and IL-6 induced CD4+CD29+
      T cell subset function in B cell antibody synthesis may be important in B cell
      hyperactivity and antibody synthesis in RA. Our studies suggest that CD4+CD29+
      subsets bearing TcR gamma delta antigens are increased at inflammation site (SF)
      in RA and is implicated in immunopathology and autoantibody production of this
      inflammatory condition in humans.

PMID- 8295174
TI  - Rheumatoid arthritis: anti-Ro antibodies define a non-HLA-DR4 associated
      clinicoserological cluster.
AB  - OBJECTIVE: To determine the clinical significance of anti-Ro antibodies in
      patients with rheumatoid arthritis (RA). METHODS: Cross sectional study of 278
      consecutive patients with RA at a single academic rheumatology center. Clinical
      data were collected without knowledge of the anti-Ro status. Anti-Ro antibodies
      were detected in coded sera using immunoprecipitation of HeLa cell extracts.
      RESULTS: Ten (3.6%) of the 278 patient sera were found anti-Ro positive. Age,
      sex, duration of disease, prevalence of rheumatoid factor (RF), and severity of
      joint involvement were similar in anti-Ro positive and negative patients. Anti-Ro
      positive patients had significantly more symptomatic Sjogren's syndrome (SS),
      leukopenia, hypocomplementemia, vasculitic purpura, and photosensitivity (odds
      ratio [OR] varying from 7.3 to 26.8). Although SS was frequent in anti-Ro
      positive patients with RA, secondary SS was not independently linked to any of
      the associated extraarticular manifestations. Histocompatibility studies revealed
      the absence of HLA-DR4 in the 8 anti-Ro positive patients available for typing
      and the presence of DR2 and/or DR3 in 6 of them. CONCLUSIONS: Immunoprecipitating
      anti-Ro antibodies in serum delineate a clinical, non-HLA-DR4 associated cluster
      of patients with RA almost as numerous as systemic lupus erythematosus or primary
      SS. Production of these antibodies seems to precede clinical manifestations and
      may thus have prognostic implications.

PMID- 8295175
TI  - Levels of urinary polyamines in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To compare urinary polyamine levels in patients with rheumatoid
      arthritis (RA), with osteoarthritis (OA), and in healthy controls and examine the
      relationship between urinary polyamine levels and several disease variables in
      patients with RA. METHODS: We determined the concentrations of urinary polyamines
      in 33 patients with RA, 24 with OA, and 20 healthy controls, using the enzymatic
      assay method. For patients with RA relevant clinical and laboratory variables
      were obtained and functional and radiologic scores determined for the joints.
      RESULTS: Urinary polyamine levels were significantly higher in patients with RA
      versus those with OA and healthy controls. In patients with RA the levels of
      urinary polyamines correlated significantly with the concentrations of serum C
      reactive protein (CRP); there was also a statistically significant negative
      correlation between their urinary polyamine levels and average grip strength in
      either hand. Moreover, the levels of urinary polyamines in patients with RA
      showed an increase in proportion to the degree of joint functional damage and
      radiologic progression. CONCLUSION: Our results confirm our previous report of an
      increase in the amount of free putrescine in synovial fluids and a significant
      correlation between the putrescine contents of synovial tissues and the serum CRP
      concentrations in patients with RA; they also suggest that urinary polyamine
      levels may be related to the activity and progression of RA, indicating that
      polyamine may play an important role in RA.

PMID- 8295176
TI  - Fractures in rheumatoid arthritis: an evaluation of associated risk factors.
AB  - OBJECTIVE: Our purpose was to identify factors indicative of a high fracture risk
      during the disease course of rheumatoid arthritis (RA). METHODS: In 1110 patients
      (879 women and 231 men) with RA from five Arthritis, Rheumatism and Aging Medical
      Information System centers, information from history, clinical and laboratory
      examination, outcome assessment, and therapy was evaluated for association with
      the 226 first fractures having occurred during the years from 1975 to 1988.
      RESULTS: The mean age of the patients was 54 years, the mean time of observation
      was 8 years. Multivariate analyses identified the following factors to be
      associated with fracturing: years taking prednisone, previous diagnosis of
      osteoporosis, disability, age, lack of physical activity, female sex, disease
      duration, impaired grip strength, and low body mass. CONCLUSION: We conclude that
      patients with RA at greatest risk for fracturing are easily identified by using a
      few clinical variables. These findings support encouragement of active lifestyle
      habits and avoidance of longterm administration of corticosteroids in patients
      with RA.

PMID- 8295177
TI  - How often is seropositive rheumatoid arthritis an erosive disease? A 17-year
      followup study.
AB  - OBJECTIVE: The frequency of erosiveness was studied in rheumatoid arthritis (RA)
      by longterm followup. METHODS: A community based cohort of 263 patients with
      recent onset (< or = 6 months) arthritis were followed in Heinola. At 8-year
      followup examination 113 cases were found to have rheumatoid factor positive
      (seropositive) nonspecific arthritis, and 15 were nonerosive in the radiographs.
      The 15 patients were reexamined in 1992 (17-year followup). RESULTS: Eleven of 15
      were found to have erosive disease, and of these, 6 had putative psoriatic
      arthritis, 4 RA, and one monoarthritis of the knee. Of the remaining 4
      seropositive nonerosive cases only one fulfilled the 1987 American College of
      Rheumatology (ARA) criteria for RA. CONCLUSION: In patients with seropositive RA
      with 4 1987 ARA criteria, 99% developed erosive disease.

PMID- 8295178
TI  - The ARA 1987 revised criteria select patients with clinical rheumatoid arthritis
      from a population based cohort of subjects with chronic rheumatic diseases
      registered for drug reimbursement.
AB  - We tested the traditional format of the American Rheumatism Association (ARA)
      1987 revised criteria for the classification of rheumatoid arthritis (RA) in a
      cohort of 220 subjects with drug reimbursement for chronic rheumatic diseases
      extracted from the National Sickness Insurance Register, in a community of 18,000
      people in Finland. One hundred and nine of the 193 who consented to the study
      both met the new ARA criteria for RA and had disease onset after 16 years of age,
      giving a cumulative prevalence of 0.8% in the population of 13,300 over 16 years.
      The disease of 6 of them, however, fulfilled the criteria and clinical picture of
      some other rheumatic disease. Thus 103 patients had RA as the only diagnosis. The
      female:male ratio in the 103 patients was 1.7:1. Ninety-one (88%) had
      seropositivity at some time in their disease and 99 (96%) had erosive joint
      disease. In most instances the 12 seronegatives had either mild or nontypical RA
      and only one of them was male. The 103 patients who met the new ARA criteria had
      significantly more interventions, such as hospitalization, drug treatment and
      orthopedic surgery, than the subjects (n = 42) who despite a clinician's primary
      diagnosis of RA did not fulfill the criteria. Thus the new ARA criteria
      distinguish clinical and severe cases of RA from nonclinical or non-RA cases when
      applied to a population based cohort of subjects with chronic rheumatic diseases
      registered for drug reimbursement.

PMID- 8295179
TI  - Anticardiolipin antibodies in systemic lupus erythematosus: clinical correlates,
      HLA associations, and impact on survival.
AB  - OBJECTIVE: To determine the frequency and clinical and HLA associations of
      anticardiolipin (aCL) antibodies in patients with systemic lupus erythematosus
      (SLE), as well as their impact on survival. METHODS: We studied 139 patients with
      SLE seen at a university based practice. We tested for clinical, laboratory, and
      HLA associations with levels of aCL antibody isotypes either in sera available in
      the bank (distant past) or in 2 samples. Demographic, clinical, laboratory, and
      HLA data were subjected to univariate survival analysis; variables of importance
      were entered into Cox multivariate regression analyses. RESULTS: aCL antibodies
      (any isotype) were present in 57 (41.0%) of the 139 patients tested in the
      distant past sample, and in 23 (32.3%) as a persistent event in the 71 patient
      subgroup tested twice. IgG aCL were significantly associated with deep venous
      thrombosis (DVT) (p = 0.04). No other clinical or HLA association was found with
      aCL positivity. In the survival analyses, older age at diagnosis, presence of
      major infections, endstage renal disease, and IgM aCL antibody positivity in the
      distant past emerged as important independent factors adversely affecting
      survival. In the subgroup tested twice for aCL antibodies (n = 71), persistent
      IgM aCL antibody positivity (n = 10) emerged as an important independent factor.
      Among the subgroup of patients that had HLA data available (n = 88), HLA-DQw7 and
      thromboembolic events also adversely affected survival. CONCLUSION: We confirmed
      the association of IgG aCL antibody positivity with DVT, and the impact on
      survival of endstage renal disease, major infections, and older age at diagnosis.
      IgM aCL antibody positivity present either as an isolated event in the distant
      past or as a persistent finding, thromboembolic events, and HLA-DQw7 emerged as
      important prognostic factors.

PMID- 8295180
TI  - Hypertension increases the risk of renal deterioration in systemic lupus
      erythematosus.
AB  - OBJECTIVE: To assess the effect of hypertension on the development of renal
      functional deterioration, end stage renal disease and death in patients with
      systemic lupus erythematosus (SLE). METHODS: Person-years analysis using
      regression techniques to adjust for other baseline risk factors for adverse renal
      and patient survival outcomes. RESULTS: Six hundred eighty-five patients with SLE
      were followed for a total of 4,137 person-years. The risk of renal deterioration
      (doubling of serum creatinine) and endstage renal disease (ESRD) both increased
      with increasing baseline mean arterial pressure (MAP) (both p > 0.05). Even after
      adjustment for age, sex, baseline serum creatinine, C3, erythrocyte sedimentation
      rate, hematocrit, anti-DNA antibodies, and proteinuria, those in the highest
      quartile of MAP had 2.3 times the odds of renal deterioration at 12 months and
      4.6 times the odds of ESRD compared to those in the lowest quartile of MAP (both
      p < 0.01 comparing highest to lowest quartile of MAP). Also, hypertension
      increased the risk of mortality, especially between one and 2 years after blood
      pressure determination. The effect of hypertension was also independent of
      corticosteroid dose. CONCLUSION: In patients with SLE, hypertension is a potent
      independent risk factor for adverse renal outcomes, and it also increases the
      risk of death.

PMID- 8295181
TI  - Effects of prostaglandin E1 on the production of IgM and IgG class anti-dsDNA
      antibodies in NZB/W F1 mice.
AB  - OBJECTIVE: To investigate the effects of prostaglandin E1 (PGE1) on IgM and IgG
      class anti-dsDNA antibody production by young and aged female New Zealand
      black/white (NZB/W) F1 mouse spleen cells in vitro. METHODS: Whole cells or B
      cells from NZB/W F1 mouse spleen cells were cultured with lipopolysaccharide
      (LPS) in the absence or presence of graded concentrations of PGE1 for 1 to 5
      days. After cultures, the supernatants were collected and assayed for released
      IgM and IgG class anti-dsDNA antibodies by enzyme-linked immunosorbent assay.
      RESULTS: Young (3-month-old) mouse spleen cells produced similar levels of IgM
      class anti-dsDNA antibodies, while these cells produced considerably low levels
      of IgG class anti-dsDNA antibodies compared to aged (6-month-old) mouse spleen
      cells when stimulated with LPS. PGE1 suppressed the production of IgM class anti
      dsDNA antibodies by about 50% at a concentration of 10(-6) M in both young and
      aged mouse spleen cell cultures. On the other hand, the production of IgG class
      anti-dsDNA antibodies was resistant to the inhibitory effects of PGE1.
      CONCLUSION: Our data suggest that PGE1 is effective in inhibiting the antibody
      synthesis by B cells precommitted to IgM class anti-dsDNA antibody production,
      but the production of IgG class anti-dsDNA antibody by memory B cells present in
      young and aged mice is resistant to the inhibitory effects of PGE1.

PMID- 8295182
TI  - The toxic oil syndrome and the eosinophilia-myalgia syndrome: pursuing clinical
      parallels.

PMID- 8295183
TI  - Eosinophilia-myalgia syndrome: mortality data from the US national surveillance
      system.
AB  - OBJECTIVE: To describe some of the most severe features of eosinophilia-myalgia
      syndrome (EMS) and identify potential prognostic indicators. METHODS: Systematic
      review of data from initial case reports and from followup supplemental death
      report forms forwarded to the national surveillance system administered by the US
      Centers for Disease Control (CDC). RESULTS: As of August 10, 1991 36 deaths
      related to EMS had been reported to CDC. Among all patients fitting the
      surveillance case definition for EMS, we found that patients who died were older,
      had higher absolute leukocyte and eosinophil counts, and reported a greater
      frequency of cough or dyspnea, neuropathy, hepatomegaly, leukocytosis, and
      elevated erythrocyte sedimentation rate. All patients who died had illnesses
      affecting multiple organ systems. Of the 36 patients who died, 33 (92%) had
      neuromuscular sequelae, 29 (81%) had pulmonary complications, and 23 (64%) had
      cardiac manifestations. The most commonly observed disease process leading to
      death was progressive polyneuropathy and myopathy (24 of the 36 reported deaths)
      which produced complications of pneumonia and sepsis or respiratory failure due
      to weakness; cardiomyopathy was the underlying cause of death for 4 patients,
      primary pulmonary disease for 3, sudden death attributed to arrhythmia for 2,
      stroke for 2, and septic complications of therapy for one. CONCLUSION: Although
      neuromuscular complications were the most prominent sequelae among patients
      reported to have died, this is clearly a multisystemic disease. Older age and
      involvement of more than one organ system suggest a particularly poor prognosis,
      and the neuromuscular, pulmonary and cardiovascular sequelae appear to be the
      most worrisome.

PMID- 8295184
TI  - Interferon-gamma inhibits proliferation, differentiation, and creatine kinase
      activity of cultured human muscle cells. II. A possible role in myositis.
AB  - OBJECTIVE: To investigate the effects of human interferon-gamma (IFN-gamma) on
      cultured human skeletal muscle cells. METHODS: Muscle cell cultures were treated
      with various concentrations of recombinant human IFN-gamma, and muscle cell
      proliferation, creatine kinase synthesis and muscle cell cytotoxicity were
      analyzed. RESULTS: Treatment of muscle cell cultures with IFN-gamma resulted in
      significant inhibition of myoblasts proliferation, growth, and fusion into
      multinucleated myotubes. IFN-gamma inhibited creatine kinase synthesis if applied
      before, but not after, the myoblasts begin to differentiate into myotubes. The
      effect of IFN-gamma was dose dependent and observed at a concentration of IFN
      gamma as low as 10 U/ml. Despite these cytostatic effects, IFN-gamma was not
      cytotoxic to cultured muscle cells even with very high (10,000 U/ml) IFN-gamma
      doses. CONCLUSION: IFN-gamma inhibits muscle cell proliferation and
      differentiation in vitro. These findings suggest that IFN-gamma, a T cell
      lymphokine, may inhibit muscle regeneration and the repair of injured muscle
      fibers in myositis.

PMID- 8295185
TI  - Measures to assess ankylosing spondylitis: taxonomy, review and recommendations.
AB  - OBJECTIVE: To critically review the current use and scope of measures to assess
      patients with ankylosing spondylitis (AS). METHODS: Studies in English reported
      between January, 1986 and August, 1991 were identified both through computer
      searches of Index Medicus and manual searches of bibliographies. Only studies
      where assessment of patients with AS was a main topic were included. Information
      was extracted to classify measures as (1) physician assessed, (2) patient
      reported or (3) other assessments. RESULTS: Physician assessed measures prevailed
      in 34 (79%) of the 43 studies included. Patient reported measures were mentioned
      in 29 (67%). Most physician assessed measures (67%) focussed on mobility, most
      patient reported measures (65%) focussed on discomfort. Single item global
      assessment by physician or patient, the most generic measure, was reported in 7
      (16%) and in 17 (40%) studies, respectively. One study reported a measure which
      specifically addressed the patient's priorities regarding treatment risks. Other
      measures were reported in 22 (51%) studies, i.e., laboratory tests in all 22, and
      additionally radiographs in 2, and various measures in 6 studies. Side effects
      (by reports or otherwise) were noted in 26 (60%) studies. CONCLUSION: Current
      assessment in AS incompletely encompasses the spectrum of relevant health status
      outcomes. Specifically, more attention should be paid to the patient's point of
      view.

PMID- 8295186
TI  - Another look at spinal tuberculosis.
AB  - The steady decline in tuberculosis rates in Canada has led to a certain lack of
      awareness of the disease. We describe 7 patients with culture proven spinal
      tuberculosis, seen in a teaching hospital over a 10-year period. Persistent
      spinal pain and local tenderness were the most frequent presenting findings.
      There was a mean delay in diagnosis of 5.2 (range 1-18) months from the time of
      presentation. Only 2 patients had active extraspinal tuberculous infection. Plain
      spinal radiographs were the initial diagnostic procedure of choice showing a
      destructive vertebral lesion in 5 of 7 patients. Computed tomography (CT) played
      an important role in delineating the discovertebral lesion and in demonstrating a
      paraspinal soft tissue infection in 6 (85%) of 7 patients: psoas abscess in 4 (2
      with epidural extension), epidural abscess in one, and a neck abscess in one.
      Magnetic resonance imaging (MRI) in one patient enabled a more complete
      definition of the vertebral infection and its soft tissue extensions. Two
      patients were successfully treated with combination antituberculous chemotherapy
      alone, and 5 required adjuvant surgical procedures. Our study stresses the need
      for increased alertness to this now uncommon but treatable spinal infection, and
      emphasizes the diagnostic usefulness of CT and MRI in defining subtle
      discovertebral lesions and in detecting unsuspected paravertebral soft tissue
      extension.

PMID- 8295187
TI  - Effect of phorbol ester on the inhibition of proteoglycan synthesis induced by
      interleukin 1 and antiinflammatory drugs.
AB  - Low (2 ng/ml) and high (40 ng/ml) concentrations of the protein kinase C (PKC)
      activator phorbol-12-myristate-13-acetate (PMA) were tested for their effect on
      cultured bovine articular chondrocyte proteoglycan synthesis. In addition, we
      examined whether PMA could reverse interleukin 1 (IL-1) and nonsteroidal
      antiinflammatory drug (NSAID) induced inhibition of proteoglycan synthesis. Low
      concentrations of PMA stimulated proteoglycan synthesis by chondrocytes. High
      concentrations of PMA had no significant effect. IL-1 and high concentrations of
      NSAID inhibited proteoglycan production by chondrocytes. Low concentrations of
      PMA completely reversed IL-1 induced inhibition but did not significantly alter
      proteoglycan synthesis in the presence of antiinflammatory drugs. On the other
      hand, high concentrations of PMA had little effect on IL-1 induced inhibition but
      significantly potentiated the suppression of proteoglycan synthesis induced by 2
      of the NSAID tested, indomethacin and flurbiprofen. Assay of PKC activity
      indicated that PKC levels were down-regulated by high but not by low
      concentrations of PMA. This suggests that different mechanisms were regulating
      the effects of low and high concentrations of PMA on proteoglycan synthesis.
      Although IL-1 and high concentrations of NSAID both suppress proteoglycan
      synthesis by chondrocytes, their different responses when coincubated with PMA
      suggest that they act through different pathways.

PMID- 8295188
TI  - Characterization of responders and nonresponders to tiaprofenic acid and naproxen
      in the treatment of patients with osteoarthritis.
AB  - OBJECTIVE: To characterize responders/nonresponders to 2 nonsteroidal
      antiinflammatory drugs by a combination of start variables in the treatment of
      patients with osteoarthritis (OA) of the hip(s)/knee(s). METHODS: Two hundred
      eight patients participated in a 3-week randomized double blind parallel group
      trial. RESULTS: The responder rate to tiaprofenic acid and naproxen was 52 and
      59%, respectively. Correctly characterized by use of a combination of 6 baseline
      variables were 79% of the patients treated with tiaprofenic acid and 81% treated
      with naproxen. CONCLUSION: Both active drugs were found effective compared with
      placebo in patients with OA, but with different characteristics.

PMID- 8295189
TI  - Ultrasonography of the subtalar and midtarsal joints.
AB  - An ultrasonographic method for detecting intraarticular effusion in subtalar and
      midtarsal joints was developed. An unechogenic zone in these joints is a sign of
      intraarticular effusion or synovitis. It is also possible to inject
      glucocorticoid into these small joints with the guidance of ultrasonography.

PMID- 8295190
TI  - Sleep and other symptoms in primary fibromyalgia and in healthy controls.
AB  - OBJECTIVE: To evaluate sleep architecture and self-reported complaints in
      patients with fibromyalgia (FS). Forty patients and 10 age standardized healthy
      controls were included. All participants were women. METHODS: All patients and
      controls underwent a clinical examination and gave answers to a questionnaire.
      Polysomnography was done in 20 patients and in all controls. RESULTS: The percent
      arousal time and arousal index were higher (p < 0.05 and < 0.01, respectively)
      among FS compared to controls, but no other differences were found in sleep
      architecture. Ten of the patients with FS and 2 controls showed an apnea
      hypoapnea index above 5/h (NS). The arousal time and arousal index were higher in
      patients with apnea-hypoapnea index > or = 5 compared to controls with apnea
      hypoapnea index < 5 [mean (SD)] [arousal time: 4.5 (3.2) vs 0.7 (0.7), p < 0.001,
      arousal index: 14.9 (10.8) vs 2.4 (3.7), p < 0.001]. In patients with FS with
      apnea-hypoapnea index < 5 the arousal time was higher (2.0 (1.2), p < 0.05) and
      arousal index marginally higher (5.6 (3.2), p = 0.07) compared to the controls.
      No other differences were found in sleep structure. Insomnia (difficulties
      falling asleep, maintaining sleep, early morning awakening), tiredness, mood,
      cognitive disturbances and muscular pain were all reported more commonly by
      patients with FS than controls. A subdivision of the patients with FS into those
      with apnea-hypoapnea index < 5 and apnea-hypoapnea index > or = 5 did not change
      these findings. CONCLUSION: We conclude, that patients with FS show minor
      polysomnographic findings, with a higher occurrence of arousals. The arousals
      were in part explained by respiratory abnormalities. Patients with FS have
      several complaints, including insomnia. Some of these may relate to sleep
      fragmentation. Controlled studies are a requirement in investigations of sleep
      disorders in fibromyalgia.

PMID- 8295191
TI  - Jack London. A modern analysis of his mysterious disease.

PMID- 8295192
TI  - Pilot investigation of naproxen/methotrexate interaction in patients with
      juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the potential interaction of naproxen and methotrexate
      (MTX) in children with juvenile rheumatoid arthritis (JRA). METHODS: Nine
      children with JRA served as their own control taking their usual doses of MTX
      (0.22-1.02 mg/kg/week) and naproxen (14.6-18.8 mg/kg/day) separately and in
      combination. RESULTS: MTX affected a > or = 30% change in naproxen kinetics in
      6/8 patients, while naproxen altered MTX kinetics by > or = 30% in 4/9 patients.
      CONCLUSION: MTX can alter nonsteroidal antiinflammatory drug (NSAID) kinetics in
      children with JRA and NSAID can alter MTX kinetics. NSAID toxicity should be
      considered when assessing adverse reactions in patients receiving the combination
      treatment of MTX and NSAID:

PMID- 8295193
TI  - Recurrent reflex sympathetic dystrophy as a manifestation of systemic lupus
      erythematosus.
AB  - Reflex sympathetic dystrophy (RSDS) is a syndrome of hyperesthesia and vasomotor
      disturbance of an extremity, often following trauma or an inflammatory process.
      We describe a patient with systemic lupus erythematosus (SLE) and recurrent RSDS
      involving all 4 extremities at various times during her illness. Treatments,
      including corticosteroid use, physical therapy and at times sympathetic nerve
      blockade led to the resolution of each episode. We suggest the diagnosis of RSDS
      be considered in patients with connective tissue diseases who present with
      atypical pain syndromes not attributable to their primary illness.

PMID- 8295194
TI  - Correction of thrombocytopenia with dapsone in the primary antiphospholipid
      syndrome.
AB  - A 25-year-old woman with the antiphospholipid syndrome developed severe
      thrombocytopenia (18 x 10(9)/l), which was promptly corrected by treatment with
      dapsone. The mechanisms for the apparent therapeutic effect of dapsone are
      discussed.

PMID- 8295195
TI  - Relation of antiphospholipid antibody and placental bed inflammatory vascular
      changes to the outcome of pregnancy in successive pregnancies of 2 women with
      systemic lupus erythematosus.
AB  - Histological changes in biopsies from the placental and placental bed in 2
      successive pregnancies of 2 women with systemic lupus erythematosus and
      antiphospholipid antibodies were studied. In one of the first 2 pregnancies
      vasculitis was found in the spiral arteries of the placental bed biopsy, while
      the other showed perivascular inflammatory infiltration and deciduitis. This was
      associated with poor pregnancy outcome and elevated antiphospholipid antibodies
      (aPL). In the subsequent 2 pregnancies prednisolone treatment was tailored to
      suppress the aPL titer with markedly decreased inflammatory changes and no
      evidence of vasculitis in the spiral arteries of the placental bed was found.
      This was associated with a normal pregnancy outcome. A causal relationship
      between aPL and inflammatory vascular changes in the placental bed as well as a
      beneficial effect of the corticosteroid treatment in those two women in
      suggested.

PMID- 8295196
TI  - Breast cancer with systemic manifestations mimicking Still's disease.
AB  - We describe a case whose clinical features strongly suggested Still's disease,
      which led to the discovery of breast cancer. Our patient's symptoms consisting of
      fever, joint inflammation, pleuritis, and pericarditis, were initially resistant
      to high doses of steroids, and disappeared only after the cancer was removed,
      despite rapid tapering and cessation of steroid therapy. A paraneoplastic
      phenomenon seems probable.

PMID- 8295197
TI  - Immunoblastic malignant lymphoma in adult onset Still's disease.
AB  - Lymphadenopathy commonly occurs in patients with adult onset Still's disease
      (AOSD). Besides the more common reactive hyperplasia, the histological pattern
      may occasionally be confused with that of malignant lymphoma. A case of AOSD that
      developed an immunoblastic malignant lymphoma is described. Immunohistochemistry
      showed the B cell nature of the proliferating cells. As a result, AOSD should be
      added to the list of systemic rheumatic diseases, the course of which may be
      complicated by lymphoproliferative malignancies. Our case underlines the need for
      a careful examination and of close followup to detect this eventuality earlier.

PMID- 8295199
TI  - SLE and the antiphospholipid antibody syndrome.

PMID- 8295198
TI  - Femoral periosteal thickening in pustulotic arthroosteitis, including 3-year
      followup by magnetic resonance imaging.
AB  - We describe 2 female patients with femoral periosteal thickening, in association
      with signs of pustulotic arthroosteitis in the sternocostoclavicular region and
      spine. In one patient, inflammatory changes were seen in muscular tissue
      surrounding this area of periosteal thickening, with fibrosis in the
      corresponding marrow. Over a period of up to 4 years after bone biopsy, cortical
      hyperostosis was observed spreading over a longer segment of her femoral
      diaphysis, while its thickness decreased over the longterm. Bone biopsy probably
      contributed to the striking periosteal thickening surrounded by inflammatory
      lesions in the surrounding muscles of this patients.

PMID- 8295200
TI  - Exclusion criteria for primary antiphospholipid syndrome.

PMID- 8295201
TI  - Methotrexate in psoriatic polyarthritis.

PMID- 8295202
TI  - A case of HLA-B27 negative ankylosing spondylitis treated with methylprednisolone
      pulse therapy.

PMID- 8295203
TI  - Is low dose methotrexate nephrotoxic?

PMID- 8295204
TI  - Severe aortic regurgitation in Behcet's disease.

PMID- 8295205
TI  - Gangrene as a complication of topical ice therapy.

PMID- 8295206
TI  - Design and synthesis of peptidomimetic inhibitors of HIV-1 protease and renin.
      Evidence for improved transport.

PMID- 8295207
TI  - Estrone sulfamates: potent inhibitors of estrone sulfatase with therapeutic
      potential.

PMID- 8295208
TI  - Synthesis and antifungal activity of novel cationic pneumocandin B(o)
      derivatives.

PMID- 8295209
TI  - Novel amidine-containing peptidyl phosphonates as irreversible inhibitors for
      blood coagulation and related serine proteases.
AB  - A series of new peptidyl (alpha-aminoalkyl)phosphonate diphenyl esters containing
      the 4-amidinophenyl group were synthesized and tested as irreversible inhibitors
      for thrombin and other trypsin-like enzymes. These phosphonates irreversibly
      inhibited several coagulation enzymes and trypsin. Boc-D-Phe-Pro-(4
      AmPhGly)P(OPh)2 is the best human thrombin inhibitor in the series with a
      k(obs)/[I] value of 11,000 M-1 s-1, and it inhibits thrombin more than 5-fold
      more effectively than the other enzymes tested. Z-(4-AmPhGly)P(OPh)2 is the best
      inhibitor for plasma kallikrein with a k(obs)/[I] value of 18,000 M-1 s-1.
      Generally, the (4-AmPhGly)P(OPh)2 derivatives are better inhibitors of thrombin
      and trypsin than the corresponding (4-AmPhe)P(OPh)2 derivatives which contain an
      extra CH2 separating the amidinophenyl group from the peptide backbone. The
      amidino phosphonates did not inhibit acetylcholinesterase and were chemically
      stable in neutral buffers. In addition, the inhibited trypsin derivative did not
      regain any enzyme activity after removal of excess inhibitor and incubation in a
      pH 7.5 buffer for 1 day. Boc-D-Phe-Pro-(4-AmPhGly)P(OPh)2 and D-Phe-Pro-(4
      AmPhe)P(OPh)2 prolonged the prothrombin time ca. 2-fold and prolonged the
      activated partial thromboplastin time ca. 3-4-fold in human plasma at
      concentrations of 63 and 125 microM, respectively. The novel amidine-containing
      peptidyl phosphonates reported here are thus effective anticoagulants in vitro,
      and they may have utility for use in vivo.

PMID- 8295210
TI  - Total synthesis and biological properties of novel antineoplastic
      (chloromethyl)furanoindolines: an asymmetric hydroboration mediated synthesis of
      the alkylation subunits.
AB  - 1,2-Dihydro-1-(chloromethyl)-5-hydroxy-8-methyl-3H-furano[3,2-e]in dole (CFI) as
      a novel replacement of the cyclopropylpyrroloindoline (CPI) alkylation subunit of
      CC-1065, U-71184, and U-73975 (adozelesin) has been synthesized and incorporated
      into a series of efficacious antineoplastic agents. A partial solution to an
      asymmetric synthesis of the CFI alkylation subunit has been achieved by the
      implementation of an asymmetric hydroboration reaction of an intermediate 3
      methyleneindoline (13). Extension to the asymmetric synthesis of the CBI and CI
      alkylation subunits is presented. The demonstration and comparative study of the
      sequence-selective DNA alkylation properties of the CFI-based agents are
      detailed, and the preliminary in vitro and in vivo antineoplastic properties of
      these agents in the human epidermoid cell lung carcinoma (T222) are described.

PMID- 8295211
TI  - 3-substituted thieno[2,3-b][1,4]thiazine-6-sulfonamides. A novel class of
      topically active carbonic anhydrase inhibitors.
AB  - 3-Aminoalkyl derivatives of thieno[2,3-b][1,4]thiazine-6-sulfonamide were
      prepared for evaluation as topically active ocular hypotensive agents. The
      compounds described were found to be excellent in vitro inhibitors of carbonic
      anhydrase II and in vivo to lower intraocular pressure in three rabbit models of
      ocular hypertension. Compounds 20A, 20B, and 20C met the requirement of
      formulation as a 1% solution at pH 5.2, but none of the compounds described
      exhibited greater activity in the normotensive albino rabbit, the alpha
      chymotrypsin-treated albino rabbit, or the normotensive pigmented rabbit than MK
      927 or MK-507, the present clinical candidates.

PMID- 8295212
TI  - Novel cAMP PDE III inhibitors: imidazo[4,5-b]pyridin-2(3H)-ones and thiazolo[4,5
      b]pyridin-2(3H)-ones and their analogs.
AB  - The transformation of milrinone to 1,3-dihydro-5-methyl-6-(4-pyridinyl)-2H
      imidazo[4,5-b]pyridin-2-one (13a), 5-methyl-6-(4-pyridinyl)thiazolo[4,5-b]pyridin
      2(3H)-one (51), and 7-methyl-6-(4-pyridinyl)-1,8-naphthyridin-2(1H)-one (22)
      resulted in very potent cAMP PDE III inhibitors with in vitro activity in the
      nanomolar range. 1,3-Dihydro-2H-imidazo[4,5-b]pyridin-2-ones 13 were prepared
      from 2-aminopyridine-3-carboxylic acids (7, 10) via Curtius rearrangement. 1,8
      Naphthyridin-2(1H)-one 22 and the corresponding 3,4-dihydro derivative 28 were
      prepared from 5-bromo-2-methyl[3,4'-bipyridin]-6-amine (21) and 5-bromo-2
      methyl[3,4-bipyridin]-6(1H)-one (24), respectively, via Heck reaction.
      Thiazolo[4,5-b]pyridin-2(3H)-ones 35 were prepared from 6-bromo[3,4'-bipyridin]-6
      amines 30 and 32 via a four-step sequence. Treatment of 6-amino-2-methyl[3,4'
      bipyridine]-5-thiol (59) with ethyl bromoacetate and ethyl bromodifluoroacetate
      gave pyridothiazinones 60 and 61, respectively.

PMID- 8295213
TI  - Synthesis and structure-activity studies of N,N'-diarylguanidine derivatives. N
      (1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine: a new, selective
      noncompetitive NMDA receptor antagonist.
AB  - Diarylguanidines, acting as NMDA receptor ion channel site ligands, represent a
      new class of potential neuroprotective drugs. Several diarylguanidines
      structurally related to N,N'-di-o-tolylguanidine (DTG), a known selective sigma
      receptor ligand, were synthesized and evaluated in in vitro radioligand
      displacement assays, with rat or guinea pig brain membrane homogenates, using the
      NMDA receptor ion channel site specific radioligand [3H]-(+)-5(S)-methyl-10(R),11
      dihydro-5H-dibenzo[a,d]cyclohepten-5 ,10- imine (MK-801, 3), and the sigma
      receptor-specific radioligand [3H]-di-o-tolylguanidine (DTG, 5). This paper
      presents the structure-activity relationships leading to novel tri- and
      tetrasubstituted guanidines, which exhibit high selectivity for NMDA receptor ion
      channel sites and weak or negligible affinity for sigma receptors. The in vitro
      binding results from symmetrically substituted diphenylguanidines indicated that
      compounds having ortho or meta substituents (with respect to the position of the
      guanidine nitrogen) on the phenyl rings showed greater affinity for the NMDA
      receptor ion channel site compared with para-substituted derivatives. Among the
      group of ring substituents studied for symmetrical diarylguanidines, an isopropyl
      group was preferred at the ortho position and an ethyl group was preferred at the
      meta position. Several unsymmetrical guanidines containing a naphthalene ring on
      one nitrogen atom and an ortho- or a meta-substituted phenyl ring on the second
      nitrogen atom, e.g., N-1-naphthyl-N'-(3-ethylphenyl)guanidine (36), showed a 3-5
      fold increase in affinity for the NMDA receptor ion channel site and no change in
      sigma receptor affinity compared to the respective symmetrical counterparts.
      Additional small substituents on the guanidine nitrogen atoms bearing the aryl
      rings resulted in tri- and tetrasubstituted guanidine derivatives which retained
      affinity for NMDA receptor ion channel sites but exhibited a significant
      reduction in their affinities for sigma receptors. For example, N-1-naphthyl-N'
      (3-ethylphenyl)-N'-methylguanidine (40) showed high affinity for the NMDA
      receptor ion channel site (IC50 = 36 nM vs [3H]-3) and low affinity for sigma
      receptors (IC50 = 2540 nM vs [3H]-5). Selectivity for the NMDA receptor ion
      channel sites over sigma receptors appears to be dependent upon the structure of
      the additional substituents on the guanidine nitrogen atoms bearing the aryl
      groups. Methyl and ethyl substituents are most preferred in the tri- and
      tetrasubstituted diarylguanidines. The trisubstituted guanidine, N-1-naphthyl-N'
      (3-ethylphenyl)-N'-methylguanidine (40) and its close analogues showed good in
      vivo neuroprotection and are potential neuroprotective drug candidates for the
      treatment of stroke and other neurodegenerative disorders.

PMID- 8295214
TI  - Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel
      blockers.
AB  - The synthesis and structure-activity relationships of a series of
      phenylacetamides related to N-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha
      phenylbenzeneacetamide (1) (PD85639) acting at the voltage-dependent Na+ channel
      are described. All structural variations for this study were made in the
      phenylacetic acid portion of these molecules, and the compounds were synthesized
      by coupling the appropriately substituted phenylacetic acid derivative with 3-[1
      (2,6-dimethyl)piperidinyl]-propanamine using standard methods of amide formation.
      Compounds were tested as inhibitors of [3H]batrachtoxinin binding in rat
      neocortical membranes and also as inhibitors of veratridine-induced Na+ influx in
      Chinese hamster ovary cells expressing type IIA Na+ channels. Diphenylacetic acid
      derivatives with halogenated aromatic rings (12-15) were very potent in both
      assays, while alkoxy and alkyl substitution did not affect activity (16 and 17).
      Selected compounds were tested as potential neuroprotective agents in two cell
      culture assays involving inhibition of veratridine-induced and hypoxia-induced
      lactate dehydrogenase release. Compound 15 was equipotent with flunarizine, a
      reference compound in both neuroprotection assays.

PMID- 8295215
TI  - Alpha-spirocyclopentyl- and alpha-spirocyclopropyl-gamma-butyrolactones:
      conformationally constrained derivatives of anticonvulsant and convulsant
      alpha,alpha-disubstituted gamma-butyrolactones.
AB  - To further study the putative gamma-butyrolactone site of the GABAA/chloride
      channel complex, constrained derivatives of convulsant and anticonvulsant
      alpha,alpha-disubstituted gamma-butyrolactones (alpha-spirocyclopropyl- and alpha
      spirocyclopentyl-gamma-butyrolactones) were synthesized and evaluated
      biologically. Most of the spirocyclopropyl agents were anticonvulsants when
      tested against pentylenetetrazole-induced seizures in mice. These agents
      effectively displaced 35[S]-tert-butylbicyclophosphorothionate (35[S]-TBPS), a
      ligand for the picrotoxin binding site of the GABAA/chloride channel, from rat
      neuronal membranes and affected the GABA-mediated current in hippocampal neurons.
      The monomethyl-substituted spirocyclopropyl agent with a methyl group cis to the
      carbonyl (15) potentiates GABA-induced current whereas the trans derivative (16)
      blocks the current. The only anticonvulsant in the spirocyclopentyl series was
      the unsubstituted spirocyclopentyl compound 2. All the other substituted
      spirocyclopentyl targets were inactive in vivo at the highest dose tested except
      for convulsant 9, which has a trans 2,5-dimethyl-substituted cyclopentyl ring.
      All the spirocyclopentyl derivatives displaced 35[S]-TBPS from rat neuronal
      membranes very effectively, and they also all potentiated GABA-induced chloride
      current except for convulsant 9 which blocked the current. From the data obtained
      in this investigation, it appears that when the volume occupied above and below
      the lactone ring is as large as that occupied by spirocyclopentyl agent 9,
      convulsant activity is observed. Groups with less volume in these areas either
      are inactive in the behavioral test or have anticonvulsant activity. When bound
      to the GABAA/chloride channel, the larger molecules may stabilize the closed
      state of the channel whereas the smaller molecules may stabilize the open state.

PMID- 8295216
TI  - Antitumor agents. 144. New gamma-lactone ring-modified arylamino etoposide
      analogs as inhibitors of human DNA topoisomerase II.
AB  - The trans-fused gamma-lactone ring of etoposide is readily epimerized to its cis
      epimer, which is biologically inactive, or is metabolized to the inactive ring
      opened hydroxy acids. Modification of this gamma-lactone ring of 4 beta
      (arylamino)-4'-O-demethyl-4-desoxypodophyllotoxin resulted in several compounds
      (15-16, 21-22, and 24) that should block this epimerization and the resulting
      biological deactivation. In a topoisomerase II inhibition assay, compounds 21,
      22, and 24 showed comparable activity to etoposide. In a protein-linked DNA
      complex formation assay, compounds 21 and 22 were more active than etoposide.

PMID- 8295217
TI  - Evaluation of a vitamin-cloaking strategy for oligopeptide therapeutics:
      biotinylated HIV-1 protease inhibitors.
AB  - The outstanding limitations to the oligopeptide as a therapeutic agent are poor
      oral availability and rapid biliary clearance. To address these concerns a series
      of eight peptidic HIV-1 protease inhibitors containing the structural segment of
      the vitamin biotin have been prepared. These have been evaluated with regard to
      the hypothesis that this vitamin would cloak the peptidic character of these
      oligopeptides, and thus impart to these inhibitors the potential for absorption
      and distribution via biotin transporters and receptors. By iterative optimization
      about a -Cha psi[CH-(OH)CH(OH)]Val- core inhibitory insert, three particularly
      potent inhibitors (K(i) < or = 10 nM) of the HIV-1 protease were obtained.
      Although excellent cell culture antiviral activity is observed for other peptidic
      protease inhibitors of comparable affinity, none in this series exhibited
      satisfactory antiviral activity. This failure is attributed to the
      incompatibility of the hydrophilic and hydrogen-bonding biotin segment, with the
      facile membrane permeability and intracellular access presumably required for
      antiviral activity. The ability of the biotin to cloak the peptide, and thus
      render the overall appearance of the conjugate as that of a vitamin, was
      evaluated. Four of this series were evaluated for recognition by the Caco-2 cell
      intestinal biotin transporter. None inhibited competitively biotin uptake,
      indicating a lack of recognition. A vitamin may bind to a specific protein
      carrier, and thus attain an improved serum profile (by resistance to biliary
      clearance) and advantageous delivery to cells. Therefore, the serum
      concentrations of three were evaluated following an iv bolus in a rat model for
      serum clearance. One of the three protease inhibitors (L-idonamide, 6-cyclohexyl
      2,5,6-trideoxy-2-(1-methylethyl)-5-[[3-methyl-1-oxo-2-[[5- (hexahydro-2-oxo-1H
      thieno[3,4-d]imidazol-4-yl)-1- oxopentyl]amino]butyl]amino]-N-[2-methyl-1-[[(2-
      pyridinylmethyl)amino]carbonyl]butyl]-, [3aS-[3a alpha, 4 beta (1R*,2R*,3R*),6
      alpha]]-) sustained a more than 5-fold increase in serum concentration at all
      time points relative to the benchmark structure. The remaining two had serum
      concentrations at least equal to the benchmark, suggestive of improved resistance
      to clearance. One (L-idonamide,6-cyclohexyl-2,5,6-trideoxy-5-[[2-[[5-(hexahydro-2
      ox o-1H- thieno-[3,4-d]imidazol-4-yl)pentyl]thio]benzoyl]amino]-2-(1-
      methylethyl)-N-[2-methyl-1-[[(2-pyridinyl- methyl)amino]carbonyl]butyl]-, [3aS
      [3a alpha, 4 beta(1R*,2R*),6a alpha]]-) was prepared as a complex with the biotin
      binding protein avidin. Avidin may resemble an endogenous serum biotin carrier
      protein.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8295218
TI  - Adenosine deaminase inhibitors. Synthesis and biological evaluation of 4-amino-1
      (2(S)-hydroxy-3(R)-nonyl)-1H-imidazo[4,5-c]pyridine (3-deaza-(+)-EHNA) and
      certain C1' derivatives.
AB  - The synthesis of the title compound (15) and its 1'-fluoro (14) and 1'-hydroxy
      (12) derivatives is described. Key intermediate 10 was obtained by two routes
      through condensation of (2R,3R)-3-amino-1,2-O-isopropylidene-1,2-nonanediol (3)
      with either 2,4-dichloro- or 4-chloro-3-nitropyridine. When assayed as adenosine
      deaminase inhibitors, 15 was found to be almost twice as active as its racemate.
      While hydroxylation at the 1'-position resulted in an 80-fold decrease in
      activity, the 1'-fluoro derivative proved to have activity comparable to that of
      3-deaza-(+)-EHNA.

PMID- 8295219
TI  - Tetrapeptide CCK agonists: structure-activity studies on modifications at the N
      terminus.
AB  - We had reported earlier on a novel series of potent and selective tetrapeptide
      cholecystokinin-A (CCK-A) agonists of the general structure Boc-Trp-Lys[epsilon
      Y]-Asp-N(R)PheNH2 [Y = amides, ureas; R = H, Me] that were potent anorectic
      agents in rats. In an effort to optimize the potency, selectivity, stability, and
      efficacy of our lead candidate A-71623 [R = Me, Y = o-tolylaminocarbonyl; Tac]
      toward development of a clinical candidate, we have explored a series of
      analogues in which the N-terminal Boc functionality was systematically replaced
      with various amides, ureas, carbamates, and sulfonamides of differing size,
      hydrophobicity, and stereoelectronic properties. In general, these analogues
      maintained good potency and selectivity for the CCK-A receptor (guinea pig
      pancreas), as well as potent anorectic activity in rats. Those analogues
      exhibiting equal or superior activity compared to A-71623 but differing
      physicochemical properties may represent superior drug candidates.

PMID- 8295220
TI  - A new approach to the design of sigma-2-selective ligands: synthesis and
      evaluation of N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-
      pyrrolidinyl)ethylamine-related polyamines at sigma-1 and sigma-2 receptor
      subtypes.
AB  - A series of polyamines based on the high affinity sigma receptor ligand N-[2-(3,4
      dichlorophenyl)-ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) were developed
      and evaluated for their binding characteristics at sigma-1 and sigma-2 receptor
      subtypes. The data indicated that a considerable degree of structural variation
      is possible while still retaining nanomolar affinity at sigma receptors. As the
      structure of the polyamines was varied, their binding at sigma-1 and sigma-2
      subtypes showed quite different and in some cases opposite trends, supporting the
      belief that these are pharmacologically distinct entities. Polyamines containing
      two nitrogen atoms showed optimal binding at both sigma-1 and sigma-2 receptor
      subtypes. Although additional nitrogen atoms resulted in decreased affinity at
      sigma-1 and sigma-2 subtypes, an increase in selectivity for sigma-2 subtypes was
      evident; the parent 3 showed greater selectivity for sigma-1 subtypes.
      Internitrogen spacings had a large effect on binding affinity and subtype
      selectivity. For example, the difference between N-[3-(1-pyrrolidinyl)propyl]-N'
      (3,4-dichlorobenzyl)-N,N'- dimethylethylenediamine (8) [K(i) = 29.9 nM at sigma-1
      receptor and 18.3 nM at sigma-2 receptor] to N-[3-(1-pyrrolidinyl)propyl]-N'-(3,4
      dichlorobenzyl)- N,N'-dimethylethylenediamine (10) [K(i) = 1.49 nM at sigma-1
      receptor and 12.1 nM at sigma-2 receptor] illustrates the importance of
      internitrogen spacing. Triamines 11 and 13 [Ki(sigma-2)/K(i)(sigma-1) = 0.19 and
      0.10, respectively] containing the N-N-N-Ar spacings 3-3-2 and 4-4-2, proved to
      be the most sigma-2 subtype selective of the 15 polyamines examined in this
      study. The N-N-N spacings appear to be an important factor in their sigma-2
      subtype selectivity. These compounds will serve as templates in the design of
      still further sigma-2 subtype selective ligands. The pyrrolidine ring (present in
      most of the polyamines tested in this series) proved to be an important
      recognition site for sigma receptor binding activity. Furthermore, alkyl
      substitution also appears to be important since the stripped down polyamines N-[2
      (3,4-dichlorophenyl)ethyl]ethylenediamine (15) and N1-[2-(3,4
      dichlorophenyl)ethyl]diethylenetriamine (16) exhibited relatively low binding
      affinity.

PMID- 8295221
TI  - Synthesis and biological evaluation of 5-[[3,5-bis(1,1-dimethylethyl)- 4
      hydroxyphenyl]methylene]oxazoles, -thiazoles, and -imidazoles: novel dual 5
      lipoxygenase and cyclooxygenase inhibitors with antiinflammatory activity.
AB  - A variety of benzylideneoxazoles, -thiazoles, and -imidazoles derived from 2,6-di
      tert-butylphenol were prepared and evaluated as dual inhibitors of 5-lipoxygenase
      and cyclooxygenase in rat basophilic leukemia (RBL-1) cells. The target compounds
      exhibit varying degrees of selectivity toward the two enzymes. Several compounds
      are orally active in the rat carageenan footpad edema (CFE) and mycobacterium
      footpad edema (MFE) antiinflammatory models. Structure-activity relationships are
      discussed. From this work, (Z)-5-[[3,5-bis(1,1-dimethylethyl)-4- hydroxyphenyl]
      methylene]-2-imino-4-thiazolidinone methanesulfonate salt (CI-1004) was
      identified as a potent dual inhibitor of 5-lipoxygenase (IC50 = 0.77 microM) and
      cyclooxygenase (IC50 = 0.39 microM), with oral activity (ID40 = 0.6 mg/kg) in the
      rat MFE model of inflammation.

PMID- 8295222
TI  - Development of a natural degradable polymer for orthopaedic use.
AB  - Currently, there are a large variety of degradable polymers available for use in
      surgery, which are generally based on blends and copolymers of poly(L-lactide)
      (PLLA) and poly(L-glycolide) (PGA). The major demand for these materials is for
      suturing of wounds, but the materials are also being developed for use in
      orthopaedic surgery for fracture reduction. The development of these materials is
      on two fronts, the first involving conventional fracture fixation design of
      plates. The second is to produce simple devices such as rods and to use the
      degradable materials for treatment of specific fracture types such as fractures
      of the olecranon. These materials have the advantage of possessing initially
      enhanced mechanical properties, although their relatively quick degradation
      profile diminishes these properties. As an alternative we are developing
      polyhydroxybutyrate (PHB) and its copolymers with polyhydroxyvalerate (PHV). This
      range of polymers mab be easily thermally processed, are very cheap and easily
      available. The polymer also has the significant advantage of being piezoelectric.
      This is discussed.

PMID- 8295223
TI  - An electromechanical breathing device for minimal particle loss while inhaling
      aerosols.
AB  - The design of an electromechanical breathing mask that minimizes particle loss
      during inhalation of aerosols from a provocation box is described. The device
      measures air flow by means of an anemometer. A provocation example is depicted
      and the possibility of measuring the provocation dose is discussed. The breathing
      device here described has been shown to be easy to use and to give reliable
      results.

PMID- 8295224
TI  - Design and development of a biomechanical apparatus to test the integrity of the
      Luque orthopaedic internal bone-plate fixation system.
AB  - This paper describes the design and construction of a biomechanical model that
      will determine the pull-out strengths and fatigue failure of internal fixation
      devices used at the lumbosacral junction. Fusions at this junction have the
      highest failure rate. It is suggested that devices that successfully fix this
      vertebral unit will be effective at other levels of the spine. A model that tests
      any device designed for use at the lumbosacral junction will therefore provide a
      uniform measure of the effectiveness of different kinds of instrumentation at the
      L5-S1 vertebral unit. It will also provide predictive values for fixation systems
      at other spinal levels. A real-time data-acquisition system was also designed and
      used to define and determine the failure of the Luque orthopaedic bone-plate
      fixation device.

PMID- 8295225
TI  - A gas monitoring system for ethylene oxide sterilizers with constant sample flow
      through a microwave cavity spectrometer.
AB  - This paper reports a measurement system for monitoring the gas concentrations of
      ethylene oxide (EO) within sterilizers. It samples gas from the sterilizer
      chamber at a constant flow into a microwave cavity spectrometer. The pressure in
      the cavity of the spectrometer is linearly proportional to that in the sterilizer
      chamber, hence the partial pressure (i.e. gas concentration) of the EO gas is
      linearly proportional to that in the chamber. Measurement of the gas
      concentration in the chamber can therefore take place without the need to monitor
      and interpret the chamber pressure. As a consequence the reliability of the
      sterilization process may be improved, thus enabling a reduction in the in
      chamber concentration of EO during sterilization and, hence, EO residues. The
      microwave cavity spectrometer operates under conditions of power saturation, and
      there is a good linear correlation between the output signal and the
      concentration of EO in the gas cell (to within a standard error of 4%).

PMID- 8295226
TI  - Toxicokinetics: its significance and practical problems.

PMID- 8295227
TI  - Effect of dimethyl sulfoxide pretreatment on activities of lipid peroxide
      formation, superoxide dismutase and glutathione peroxidase in the mouse liver
      after whole-body irradiation.
AB  - We investigated the effects of dimethyl sulfoxide (DMSO) on radiation damage in
      the mouse. DMSO (i.p. 0.11 g/mouse) administered 30 min before exposure protected
      the mice from the gamma-whole body irradiation: the 30 days lethality was
      significantly decreased from 44% to 16% (P < 0.05). The contents of
      thiobarbituric acid reactive substances(TBA-RS) in the mouse liver increased
      linearly between days 2 and 10 after 9 Gy gamma ray irradiation. The TBA-RS
      contents in the liver on days 2 to 10 after irradiation were reduced by DMSO
      pretreatment. The irradiation decreased superoxide dismutase (SOD) activity in
      the liver on day 10. Decrease in SOD activity was prevented by DMSO pretreatment.
      In the electron microscopic study, the mitochondria in the irradiated mouse liver
      were swollen, but we could observe no change after DMSO pretreatment. The results
      suggest that DMSO has radioprotective effects, probably due to inhibition of
      lipid peroxidation.

PMID- 8295228
TI  - Toxicokinetics of phenobarbital in rats with DL-ethionine-induced liver injury.
AB  - The toxicokinetic parameters of phenobarbital (PB) were assessed in a female rat
      model of liver disease. In a preliminary study to determine the optimum dose of
      DL-ethionine (ET) for creating liver damage, intraperitoneal injection of 250,
      500, or 1,000 mg/kg of ET was done for 4 days. ET treatment caused an increase in
      serum GOT and GPT activity and a decrease in the serum glucose concentration. In
      the liver, triglycerides and free fatty acids were increased and glucose and S
      adenosylmethionine (SAM) were decreased. Histologic examination revealed diffuse
      fatty degeneration of the hepatocytes. These findings accorded with those already
      reported as characteristic of ET intoxication. The toxicokinetic parameters for
      PB were determined after oral or intravenous administration of 100 mg/kg of PB to
      rats with ET (500 mg/kg, i.p.)-induced hepatotoxicity. After oral administration
      of PB, prolongation of the Tmax, increased AUC0-infinity, and decreased ke and CL
      values were noted in ET-treated rats. When PB was given intravenously, the AUC0
      infinity was increased while the values of alpha, beta and CL were decreased. A
      high level of urinary excretion of PB persisted for 48 hr. Protein binding of PB
      was unchanged in ET-treated animals, but the extent of bioavailability of PB
      tended to increase. These results indicate that elimination of PB was impaired in
      the ET-treated rats.

PMID- 8295229
TI  - Effects of hydrochloric acid on the development of enterochromaffin-like (ECL)
      cell hyperplasia in the rat stomach induced by omeprazole.
AB  - In the present study, gastric pH was lowered by hydrochloric acid to investigate
      whether the cause of enterochromaffin-like (ECL) cell hyperplasia was due to the
      inhibition of acid secretion by omeprazole or due to the direct action of the
      drug. Omeprazole was given to female Crj:CD (SD) rats in a daily oral dose of 2
      or 8 mg/kg for 13 weeks, and 20 ml/kg of 0.12 N HCl was further given orally to
      the animals 3 and 6 hours after each dosing. The animals were killed at the end
      of the dosing period, and the stomach was removed and weighed. The thickness of
      the gastric wall was measured and ECL cell count and area rate of the cells were
      calculated with an image analyzer. There were no effects of the treatment with
      HCl on stomach weight or thickness of the gastric wall, but ECL cell count and
      area rate of the cells decreased markedly by the treatment with HCl. Therefore,
      the cause of gastric ECL cell hyperplasia induced by omeprazole was suggested to
      be sustained high gastric pH levels.

PMID- 8295230
TI  - Studies on the therapeutic effect of 2-pyridine aldoxime methiodide (2-PAM) in
      mammals following organophosphorus compound-poisoning (report III): distribution
      and antidotal effect of 2-PAM in rats.
AB  - The metabolic fate of 2-PAM and its antidotal effect on organophosphorus compound
      poisoning in rats were studied. When 14C-2-PAM was administered intravenously,
      the amount of 14C reaching the brain was small. Following administration by
      intramedullary injection, 14C was present in high concentrations in the brain,
      and 72-90% of the 14C present in the brain corresponded to the unchanged form of
      2-PAM. 2-PAM was rapidly excreted into the urine and feces following either
      intramedullary or intravenous administration. The half-life of 2-PAM in the brain
      following intramedullary administration was 1.52 hr. Intramedullary
      administration of 2-PAM to rats poisoned with fenitrothion or malathion enabled
      their survival and induced reactivation of brain cholinesterase.

PMID- 8295231
TI  - Reduction of bacterial translocation and intestinal structural alterations by
      heparin in a murine burn injury model.
AB  - Burn injury produces acute gastrointestinal (GI) derangements that may predispose
      the burn victim to bacterial translocation (BT). We studied the effects of
      heparin on gastrointestinal (GI) anatomic alterations and BT after 25% and 32%
      total body surface area (TBSA), full-thickness murine burn injuries. Heparin (100
      U/kg) was administered with 1 mL of normal saline (NS) resuscitation solution
      immediately postburn and 4 hours and 18 hours postburn in volumes of 0.5 mL NS.
      Mice with 25% TBSA burns treated with heparin maintained small intestine weight,
      measured 24 hours postburn, and ileal mucosal height was preserved, whereas
      burned, untreated mice lost organ weight and mucosal height. Bacterial
      translocation was decreased in mice with 25% TBSA burn injuries treated with
      heparin (35.0% vs. 10.7%, p < 0.025). After 32% TBSA burn injuries, BT was also
      decreased in heparin-treated animals (64.3% vs. 31.6%; p < 0.025). Analysis of
      mixed venous blood gases showed that heparin did not affect the severe metabolic
      acidosis that follows burn injury in this animal model, indicating that general
      tissue perfusion was not improved. Heparin administered in the acute postburn
      period ameliorates GI structural and functional damage in this murine burn model
      and decreases BT.

PMID- 8295232
TI  - Attitudes of surgical residents toward trauma care: a Canadian-based study.
AB  - Surgical residents (n = 330) registered in training programs in the province of
      Ontario, Canada were surveyed about their attitudes toward trauma care related
      issues. Questionnaires were returned by 48%. Overall, 84% felt that their
      clinical exposure to trauma was adequate; 78% noted that the emphasis placed on
      trauma topics in their educational programs was appropriate; 50% spend > 10% of
      their current clinical time in trauma care. Orthopedic residents (n = 43) were
      different; 79% devoted > 10% and 29% > or = 30% of their time to trauma. Future
      clinical activity in trauma as practicing surgeons was expressed by 83% of the
      trainees: 31% intended < 10%, 46% 10%-30%, and 6% > 30% of their future practices
      to be related to trauma. The major positive factors of trauma were the scope and
      excitement of trauma care. The major negative factors were the night/weekend
      activity and the time away from family. We are encouraged by the results of this
      survey in that a significant number of residents perceive trauma as a clinical
      endeavor to be incorporated into their future surgical practices.

PMID- 8295233
TI  - Civilian gunshot wounds--outpatient management.
AB  - Cost containment is important in this time of inner-city economic and health-care
      crisis. Of 28,150 patients treated for gunshot wounds (GSWs) from 1977 through
      1991, 16,892 (60%) were treated as outpatients after emergency department
      evaluation and treatment. The complication rate was 1.8% (mostly infections), and
      nine patients were later found to have vascular injuries requiring surgical
      treatment. These were identified later at outpatient follow-up and treated with
      no long-term morbidity or mortality. A conservative estimate of the cost savings
      from this study was more than $37 million. With a more liberal use of angiography
      to eliminate rare missed vascular injuries, many GSW victims can be safely
      treated as outpatients, eliminating the need for expensive in-hospital
      observation.

PMID- 8295234
TI  - A simple technique for anchoring tubes to the skin.
AB  - The author describes a simple technique for anchoring various tubes used in the
      treatment of trauma patients (gastrostomy tubes, jejunostomy tubes, intercostal
      drains, etc.) to the skin with sutures. In this technique the tube is stretched
      while the suture is tied around it, thus producing a tight fit.

PMID- 8295235
TI  - Lightning strike to the head: case report.
AB  - A case is presented of a teen-aged athlete who sustained a direct lightning
      strike to the head while wearing a football helmet. The helmet, the presence of
      sweat, and aggressive resuscitation were instrumental in his survival and
      complete recovery. This appears to be the first documentation of a lightning
      strike to an individual wearing protective headgear.

PMID- 8295236
TI  - The nonsurgical management of a penetrating orbitocranial injury reaching the
      brain stem: case report.
AB  - Penetrating and perforating periorbital puncture wounds by lead pencils are not
      rare, but ones that reach the brain stem are extremely unusual. We recently
      treated a patient with of this type of injury. A newly sharpened lead pencil was
      accidentally introduced through the subconjunctiva at the inner canthus of the
      right eye. It passed along the medial border of the globe transorbitally and went
      through the superior orbital fissure into the temporal fossa, then continued
      through the lateral side of the sella and posterior clinoid, reaching the brain
      stem. The entire pencil was removed inch by inch without incident under CT
      control. Meanwhile, the operative team remained ready in case of emergency
      bleeding. The patient's postoperative course was uneventful, but the initial
      neurologic deficit of the patient remained fixed.

PMID- 8295237
TI  - Reflex sympathetic dystrophy of the head: case report and discussion of
      diagnostic criteria.
AB  - The case of a patient who was involved in a car crash is presented. On the right
      side her wrist and zygomatic arch were fractured. At both localizations she
      developed a painful syndrome. The diagnosis of reflex sympathetic dystrophy of
      her arm was made within 3 weeks after the injury and therapy instituted. The pain
      in her face and skull were accompanied by vasomotor changes which increased after
      exercise and by hypesthesia, hyperpathia, paresis, and hyperhidrosis. Disorders
      of the cranial nerves were excluded by physical examination and electromyography
      and structural disorders by CT scanning. The diagnosis reflex sympathetic
      dystrophy of the head was made one year after the injury. The problems in
      diagnosis are discussed.

PMID- 8295238
TI  - Complete fracture-dislocation of the thoracic spine without neurologic deficit:
      case report.
AB  - A case is presented of a motorcyclist who crashed and suffered a fracture
      dislocation of the mid-thoracic spine without any neurologic deficit. The injury
      was discovered 6 weeks after the crash. The patient underwent surgical
      stabilization and correction of the kyphotic deformity with Luque rods and
      sublaminar wires and had an uneventful recovery.

PMID- 8295239
TI  - Transesophageal echocardiography in the evaluation of a transmediastinal gunshot
      wound: case report.
AB  - Transesophageal echocardiography is a safe, minimally invasive imaging modality
      that may be useful in the evaluation of transmediastinal gunshot wounds. In this
      report, we describe a hemodynamically stable patient who sustained a gunshot
      wound to the ascending aorta. Routine diagnostic evaluation, including
      aortography, failed to confirm the suspected diagnosis. Transesophageal
      echocardiography definitively detailed the injury to the aorta enabling
      definitive surgical repair.

PMID- 8295240
TI  - Brachial plexus palsy secondary to stress fracture of the first rib: case report.
AB  - An extremely rare case of brachial plexus palsy from a stress fracture of the
      first rib is reported. The palsy was caused by pressure exerted by excessive
      callus formation following nonunion. Conservative treatment was unsuccessful, but
      surgical decompression led to complete resolution of symptoms.

PMID- 8295241
TI  - Successful roadside resuscitative thoracotomy: case report and literature review.
AB  - Patients with injuries severe enough to require cardiopulmonary resuscitation
      (CPR) have a dismal prognosis. Time to surgical intervention is a major
      determinant of outcome in moribund trauma patients who have a potential for
      survival. With the exception of endotracheal intubation during evacuation to
      surgical intervention, no other usual prehospital procedures have been validated
      to affect outcome in such cases of extremis. This is a report of a case in which
      resuscitative surgical techniques were extended successfully to the prehospital
      environment. The patient was a 30-year-old man in extremis after a stab wound to
      the left chest. Estimating a transport time of 15 minutes, a physician riding
      with the emergency medical service (EMS) crews elected to perform a resuscitative
      thoracotomy. Following digital aortic compression, the patient regained both
      blood pressure and consciousness by the time of arrival at the trauma center. A
      left lower lobectomy was then performed in the operating room. The patient
      recovered fully and was discharged home in 21 days, neurologically intact. Four
      years later, the patient was alive, healthy, and working. This report
      demonstrates the feasibility of prehospital thoracotomy and raises provocative
      issues regarding future intense surgical involvement in prehospital care.

PMID- 8295242
TI  - Pediatric transesophageal echocardiography in the evaluation of acute disruption
      of the mitral valve following blunt thoracic trauma: case report.
AB  - Disruption of the mitral valve following blunt thoracic trauma has been only
      occasionally reported. A case of a pediatric patient with this complication is
      presented and the value of transesophageal echocardiography in diagnosis and
      management is documented.

PMID- 8295243
TI  - Fracture-dislocation of the shoulder in a child: case report.
AB  - This is a case of an 11-year old girl with a delayed diagnosis of a shoulder
      fracture-dislocation. Shoulder dislocations are rare, and proximal humerus
      fractures are uncommon. A fracture-dislocation in a child is, to our knowledge,
      as yet unrepresented in the English-language literature. The child's injury
      resolved without recurrence.

PMID- 8295244
TI  - Baluster entrapment avulsion of the little finger: a new clinical entity--case
      reports.
AB  - Five cases of avulsion injuries of the little finger are described. The mechanism
      of injury was identical in all cases. The little finger was entrapped by a
      baluster when the patient frantically attempted to grasp the handrail to avoid
      falling down stairs. To our knowledge, this type of injury has not been reported
      previously.

PMID- 8295245
TI  - Routine prophylactic antifungal agents (clotrimazole, ketoconazole, and nystatin)
      in nontransplant/nonburned critically ill surgical and trauma patients.
AB  - A prospective, randomized study was conducted to determine if prophylactic
      antifungal agents prevented yeast colonization (YC) or yeast sepsis (YS), or if
      they diminished mortality in 292 critically ill adult (nontransplant/nonburned)
      surgical and trauma patients admitted to the SICU for 48 hours or longer.
      Patients were randomized to receive (group I) no therapy, (group II) clotrimazole
      10 mg three times a day, (group III) ketoconazole 200 mg per day, or (group IV)
      nystatin 2 million units every 6 hours. For comparison patients were stratified
      by the criteria of Slotman and Burchard into high risk (> or = 3 risk factors)
      and low risk (< 3 risk factors). Fifty patients (17%) had yeast colonization,
      nine (3.1%) had yeast sepsis, and 41 (14%) died. Stepwise logistic regression
      analysis of yeast colonization and sepsis using the variables APACHE II scores >
      10, need for ventilator support > 48 hours, and 14 risk factors (Slotman and
      Burchard) showed that treatment with three or more antibiotics, APACHE II > 10,
      and ventilatory support > 48 hours were the only three variables that were
      significant predictors of yeast colonization and sepsis. There was no significant
      difference between the four groups with regard to YC (23%, 18%, 12%, and 15%,
      respectively), YS (3%, 1%, 2%, and 7%, respectively), or mortality (15%, 14%, 6%,
      and 20%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295246
TI  - The effects of albumin administration on microvascular permeability at the site
      of burn injury.
AB  - In a canine hind leg model, lymph flow (QL), lymph (CL), and plasma (CP) total
      protein concentrations, the reflection coefficient for total proteins (sigma d),
      and the filtration coefficient (Kf) were determined before and for 6 hours after
      a 5-second 100 degrees C hind paw scald (3% total body surface area, TBSA).
      Before injury, hind leg venous pressure was elevated and maintained by outflow
      restriction until a minimal, steady-state CL/CP ratio was achieved. Albumin (5%)
      was infused 30 minutes after the scald at low (0.4 mL/kg/% TBSA) or high (2
      mL/kg/% TBSA) doses. Scald uniformly increased QL, CL/CP, Kf, and paw weight gain
      (PWG). Whereas postburn infusion of low-dose albumin mildly attenuated increases
      in CL/CP and PWG noted in scald-alone animals, no differences were noted between
      the scald and scald/high-dose albumin groups.

PMID- 8295247
TI  - A comprehensive analysis of craniofacial trauma.
AB  - A review of the literature identified a need for a prospective study of the
      complete range of craniofacial trauma. The aims of this study were to determine
      the incidence, etiology, and mechanisms of craniofacial and associated injuries,
      enabling a greater understanding of their range and magnitude. Nine hundred fifty
      consecutive patients seen at an urban university hospital with any degree of
      craniofacial trauma were prospectively investigated. Craniofacial trauma was
      found to be very common at all ages. The causes were directly related to age,
      sex, and alcohol consumption, and determine the type and severity of injury. The
      commonest cause of soft-tissue injury was falls, whereas that of fractures was
      interpersonal violence. Falls accounted for most of the injuries in children and
      the elderly, whereas interpersonal violence was mainly responsible for those
      occurring in patients aged 15 to 50 years. Interpersonal violence mostly involved
      young male adults: fights occurring mainly between strangers who had consumed
      excessive amounts of alcohol. Women were usually assaulted by assailants known to
      them, their partners. Pedestrians showed a propensity to sustain cranial
      fractures, whereas motor vehicle occupants tended to sustain midfacial fractures
      and bicyclists mandibular fractures. Pedestrians incurred the severest injuries
      of all road users, and a significant proportion of road user collisions involved
      bicyclists. Sports were responsible for a significant proportion of craniofacial
      injuries in youths and young adults. Craniofacial soft-tissue injuries overall
      occurred most frequently on the forehead, nose, lips, and chin, and a method for
      their classification is proposed. The commonest craniofacial fracture was that of
      the nasal bones (45%), followed by cranial bones (24%), mandible (13%), zygoma
      (13%), orbital blow-out (3%), and maxilla (2%). The incidence of craniofacial
      trauma can be greatly reduced by improvements in interior home design, school
      education in alcohol abuse and handling potentially hostile situations
      (especially for men), improvement in automotive safety devices and compliance by
      motor vehicle occupants, and utilization of full-face helmets by bicyclists and
      motorcyclists.

PMID- 8295248
TI  - A treatment protocol for mandible fractures.
AB  - Mandibular fracture management has evolved over several decades, and
      controversies exist over ideal approaches for individual fractures. Treatment
      choices include closed versus open techniques, reduction methods and repair, and
      decision concerning intermaxillary fixation. Both the patient and the fracture
      characteristics have an impact on these choices. Patient factors include age,
      mandibular bone quality, dentition, patient reliability, and associated injuries.
      Fracture characteristics include favorability versus unfavorability, single
      versus multiple, location, and infection. This study was undertaken to develop
      and evaluate a management algorithm to determine the best treatment of mandible
      fractures. Sixty-seven patients were managed at the Grady Memorial Hospital
      otolaryngology service. Ages ranged from 3 to 68 years and included 55 male
      patients and 12 female patients. Forty-three patients had multiple fractures,
      while 24 had single fractures. Sixty-four patients were successfully managed and
      had normal function on follow-up examination. Eleven patients (16.4%) had
      complications. These included three infections, one malunion, two malocclusions,
      and five marginal nerve pareses. Multiple fractures did not have a higher
      incidence of complication. This protocol allows an orderly approach to the
      successful outcome of mandibular fractures.

PMID- 8295249
TI  - The role of echocardiography in blunt chest trauma: a transthoracic and
      transesophageal echocardiographic study.
AB  - Previous studies assessing the value of transthoracic echocardiography (TTE) in
      blunt chest trauma are limited because patients with severe chest wall injury
      often have suboptimal echocardiographic findings. Transesophageal
      echocardiography (TEE) can provide high quality images when the transthoracic
      image quality is poor. To provide complete echocardiographic assessment of
      cardiac structure and function we prospectively performed TTE in 105 patients
      with severe blunt chest trauma and TEE in 20 of the 105 patients (19%) whose TTE
      examination results were suboptimal. Myocardial contusion was diagnosed in 31
      patients (30%), 22 by TTE and nine by TEE. Cardiac complications developed in 8
      of 31 patients (26%) with myocardial contusion compared with 2 of 74 patients
      (3%) with normal echocardiographic findings (p = 0.001). Cardiac complications
      required treatment in only four patients. Echocardiography was of value in
      detecting severe right ventricular dysfunction as the cause of hypotension in two
      patients with suspected cardiac tamponade. Four patients with myocardial
      contusion died compared with two patients with normal echocardiographic findings
      (p = NS). No death was related to the cardiac status. In addition, TEE detected
      aortic injury in five patients, four with focal intimal tears and one with an
      aortic transection. We conclude that myocardial contusion is common following
      blunt chest trauma, rarely requires treatment, and is associated with a favorable
      prognosis. Only patients who develop cardiac complications benefit from
      echocardiography. Transesophageal echocardiography is of value when the TTE
      examination results are suboptimal and when aortic injury is suspected.

PMID- 8295250
TI  - Fiberoptic bronchoscopy for the early diagnosis of subglottal inhalation injury:
      comparative value in the assessment of prognosis.
AB  - The aim of this study was to determine the value of bronchoscopy in the early
      diagnosis of inhalation injury. A total of 130 burn patients underwent
      bronchoscopy on admission to a specialized center. In order to validate the
      method and the bronchoscopist's conclusions, they underwent staged bronchial
      biopsies. Using the histologic findings as the "gold standard," bronchoscopy
      proved to be sensitive (sensitivity, 0.79) and highly specific (specificity,
      0.94) for the diagnosis of inhalation injury. In addition, it was more reliable
      than the circumstances of the injury, the clinical findings, and complementary
      tests. In a one-dimensional analysis, bronchoscopy-proven inhalation injury was
      one of the most strongly predictive variables for the onset of ARDS and death.
      The analysis of survival curves confirmed that inhalation injury portends a bad
      outcome in burn patients. It was used to predict the likelihood of ARDS and death
      at the time of admission with a view to early specific treatment.

PMID- 8295251
TI  - Alcohol and other drugs: an assessment of testing and clinical practices in U.S.
      trauma centers.
AB  - INTRODUCTION: The American College of Surgeons' (ACS) Committee on Trauma
      recommends drug and alcohol screening as "essential" for level I and II or
      "desirable" for level III trauma centers. METHODS: Trauma centers were surveyed
      concerning alcohol and other drug testing policies and clinical practices during
      fiscal year 1989. RESULTS: Surveys were returned from 125 level I, 153 level II,
      and 38 other centers (n = 316; 47 states and the District of Columbia). Resources
      to measure blood alcohol concentrations (BAC) and perform urine drug screens were
      available in 99.4% and 96.8% of centers, respectively. In 63.7% of level I and
      level II and 47.4% of other centers, BACs were "routinely" obtained. The 63.7%
      testing rate for level I and level II centers was not significantly higher than a
      55.2% rate for such centers documented in a survey conducted 5 years earlier. In
      40.0% of level I and level II and 26.3% of other centers, drug screens were
      obtained routinely. The higher overall BAC testing policy compared with that for
      other drugs was significant (p < 0.001). Substance abuse counselors were employed
      at 59.3% of the trauma centers, a rate significantly higher than the 31.8% rate
      identified in a previous survey (p < 0.001). CONCLUSION: Despite available
      resources and repeated ACS recommendations, measurements of BACs and drug screens
      are routine in only 63.7% of level I and 40.0% of level II trauma centers.

PMID- 8295252
TI  - Evaluation of antimicrobials combined with hyperbaric oxygen in a mouse model of
      clostridial myonecrosis.
AB  - The efficacy of hyperbaric oxygen (HBO) alone and in combination with several
      antimicrobial agents was evaluated in a lethal model of gas gangrene in mice.
      Intraperitoneal administration of penicillin, imipenem, clindamycin, or
      metronidazole immediately followed inoculation of > 10(9) CFU of Clostridium
      perfringens type A in mice. Mice treated with hyperbaric oxygen were exposed
      twice a day to 100% oxygen at 303 kilopascals (kPa) pressure for 90 minutes. The
      total exposure time to HBO for surviving animals was 9 hours. Control (saline
      injected) mice treated with HBO alone did not have an enhanced survival rate when
      compared with mice exposed to air at ambient pressure. Survival of infected mice
      treated with either clindamycin or metronidazole was significantly longer than
      that of groups treated with penicillin or imipenem (p < 0.05). Hyperbaric oxygen
      alone or in combination with the four antimicrobial agents evaluated did not
      statistically improve survival of mice infected with a lethal dose of C.
      perfringens.

PMID- 8295253
TI  - Functional limitation after major trauma: a more sensitive assessment using the
      Quality of Well-being scale--the trauma recovery pilot project.
AB  - Little is known about the degree of disability and quality of life of patients
      after major trauma. We conducted a prospective study to examine the incidence and
      predictors of functional limitation (FL). Between January 1, 1990 and March 30,
      1990, 61 eligible trauma patients were enrolled in the study (admission GCS score
      > or = 12, LOS > 24 hours). Functional limitation after trauma was measured at
      discharge and 3 months after discharge using the Quality of Well-being (QWB)
      scale, a more sensitive index to the well end of the functioning continuum
      (range, 0 = death to 1.000 = optimum functioning). Functional limitation was also
      measured using a standard ADL scale (range, 17 = full function to 41 = maximum
      dysfunction). Risk factors measured were injury severity, body region, depression
      (CES-D) scale, and social support. Follow-up was achieved in 42 patients (70%).
      The mean age was 30 years, 74% were male, 52% white, 41% hispanic, and 3% other.
      The mean ISS was 15, with 69% blunt injuries and a mean LOS of 12 days. The QWB
      scores improved between discharge and follow-up; discharge mean = 0.457 (+/-
      0.048), follow-up mean = 0.613 (+/- 0.118), but the mean QWB score at follow-up
      still reflected a significant degree of functional limitation. The mean
      percentage of change in QWB scores was 34.5% (+/- 25.5%) with a range of -6.34%
      to 103.8%. The discharge mean FDS was 29 (+/- 6.2) while the follow-up FDS mean
      was 17 (+/- 3.8), reflecting that most patients at follow-up reported near
      perfect ADL functioning.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295254
TI  - Predicting in-hospital mortality after hip fracture in elderly patients.
AB  - Ninety-seven patients aged 88 +/- 4 years (range, 80-97 years) (study group), and
      74 aged 75 +/- 3 years (range, 70-79 years) (control group), were prospectively
      studied to investigate whether basic medical variables can predict in-hospital
      mortality in very old patients undergoing hip surgery because of femoral
      fracture. Mortality was 16.5% and 6.7% in the study and control groups,
      respectively (p = 0.054). In the study group, mortality was significantly
      correlated with age (p < 0.01), venous disorders (p < 0.05), malnutrition (p <
      0.0001), duration of surgery (p < 0.006), and postoperative noninfectious
      complications (p < 0.005). In the control group, age was the only significant
      correlate of mortality (p < 0.005). After exclusion of surgery-related variables,
      the logistic regression analysis confirmed the predictive role of venous
      disorders (odds ratio = 2.04, confidence limits = 1.09-3.79) and malnutrition
      (odds ratio = 6.01, confidence limits = 1.85-19.47) but not of age in the study
      group. However, the goodness-of-fit test showed that the statistical model did
      not fit the data adequately. We conclude that in-hospital mortality after hip
      surgery in the very old cannot be predicted on the basis of underlying medical
      conditions alone.

PMID- 8295255
TI  - Unstable distal radius fractures treated by modified Kirschner wire pinning:
      anatomic considerations, technique, and results.
AB  - A modified technique of percutaneous Kirschner-wire pinning for unstable distal
      radius fractures is presented. Three to four pins are placed from the radial
      styloid process toward and through the dorsal, volar, and ulnar cortices of the
      proximal fracture fragment, respectively. Rotational stability is achieved by
      bending and counterblowing of the wire ends in the styloid process. Anatomic
      studies of cadaver wrists revealed possible lesions of the superficial radial
      nerve, the cephalic vein, and the tendons of the brachioradialis muscle or the
      thumb and wrist extensors, respectively. Nevertheless, in a follow-up of 80
      patients after 1 year, no tendinous lesions nor any other serious complications
      were seen. Using the criteria of Green and O'Brien, the results were excellent in
      66.25%, good in 20%, and fair in 8.75%.

PMID- 8295256
TI  - Problems with initial Glasgow Coma Scale assessment caused by prehospital
      treatment of patients with head injuries: results of a national survey.
AB  - The rapid treatment of patients with a severe head injury often includes
      prehospital intubation and sedation, but such measures compromise the ability to
      obtain an accurate Glasgow Coma Scale (GCS) score in the emergency department
      (ED). Major head injury centers in the United States were surveyed to determine
      how they currently obtain initial GCS scores when these or other complicating
      circumstances exist. A two-page questionnaire was distributed to seven members of
      the trauma team at 17 major neurotrauma centers in which they were asked who
      usually determines the initial GCS score, where they are assessed, and when.
      Respondents were also asked how they assign scores for patients who received
      medications or were intubated before arrival at their hospital and how they score
      patients who are hypotensive, hypoxic, or have severe periorbital swelling. Most
      centers assess the initial GCS scores in their ED within 1 hour after the
      discovery of the patient by prehospital personnel. Most neurosurgeons said that
      hypotension and hypoxia are stabilized before the initial GCS scores are assessed
      and that intubated patients receive a non-numerical designation. But the majority
      of non-neurosurgical ED personnel said that they determine the initial GCS scores
      immediately after arrival of the patients in their department, regardless of
      hypoxia or hypotension. There also were significant discrepancies between
      attending neurosurgeons and their residents with regard to who actually assesses
      the GCS scores and how the scores are determined for patients who have received
      neuromuscular paralysis or sedation or who have severe periorbital
      swelling.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295257
TI  - Mandatory seatbelts: epidemiologic, financial, and medical rationale from the
      Colorado matched pairs study.
AB  - In what approximated a controlled clinical trial for efficacy of seatbelts, the
      Colorado matched pairs study examined 256 crashes meeting the following criteria:
      driver plus front-seat passenger, one belted (SB) and one nonbelted (NSB)
      occupant, and at least one occupant injured. Nearly half (119 of 256) of the SB
      partners escaped injury, while only 16% (41 of 256) of the NSB group were as
      fortunate. To ascertain a differential effect the 160 pairs discordant for injury
      were analyzed. The relative odds for injury in the SB group was 0.34 (95% Cl:
      0.24, 0.49) of that in the NSB group. Likewise, relative odds for any medical
      costs in the SB group was reduced to 0.24 (95% Cl: 0.14, 0.43) and for
      hospitalization to 0.29 (95% Cl: 0.10, 0.80). Sixty-five percent of the SB group
      had no medical costs in contrast to only 29% of the NSB group. Altogether the NSB
      group accounted for 76% of the medical costs and 72% of the hospitalizations.
      This study establishes the effectiveness of seatbelts in reducing nonfatal
      injuries using epidemiologic, financial, and medical data.

PMID- 8295258
TI  - Detection of the BCR/ABL fusion gene in chronic myeloid leukemia by RNA
      polymerase chain reaction.
AB  - The bcr/abl fusion gene in 20 patients with chronic myeloid leukemia (CML) was
      detected by RNA polymerase chain reaction, which used mRNA as the starting
      material to generate cDNA with reverse transcriptase followed by PCR
      amplification (RNA/PCR). Amplification of a sequence spanning the bcr/abl
      junction region was achieved by using peripheral blood cells as the source of
      mRNA from all 20 patients with CML, including 3 cases of Ph (-) CML, and cell
      line K562 was derived from patients with CML. No amplification was seen when
      mononuclear cells from 3 normal individuals, 2 patients with lymphoma and cell
      line HL-60 were used. The presence or absence of bcr exon 3 in the fusion mRNA
      was determined by the size of the amplified fragments. Of the 20 CML patients, 15
      showed only the 165-bp amplified band (indicating retention of bcr exon 3), one
      showed only the 90-bp amplified band, and 4 showed both 165-bp and 90-bp bands.
      Both bands were seen more frequently in blast crisis than in remission and
      chronic phase.

PMID- 8295259
TI  - Determination of IL-2 and cytotoxicity of killer cells in MTT colorimetry.
AB  - The activity of interleukin 2 (IL-2) in culture supernatants of lymphokine
      activated killer (LAK) cells and tumor infiltrating lymphocytes (TIL) as well as
      cytotoxicity of LAK cells on cultured leukemic cells were determined by MTT
      colorimetry. The results showed that higher activity of IL-2 in culture
      supernatant of LAK and TIL cells was found; it could be used to support the
      culture of IL-2 dependent cell lines. The significant cytotoxicity of LAK cells
      on leukemic cell lines could be found in vitro, and it was consistent with the
      ratio of effector cells to target cells. The number of living leukemic cells is
      consistently related with the concentration of formazan metabolite of MTT. It
      suggested that the numbers of living cells and cytotoxicity of LAK cells could be
      estimated by determination of formazan metabolite OD value.

PMID- 8295260
TI  - Cryopreservation and culture of the human fetal brain tissues.
AB  - Human embryos after 3-4.5 months of gestation were obtained with abortion. The
      brain tissue of the bodies was scissored up to obtain 1-3 mm3 pieces, and 7%
      dimethyl sulfoxide (DMSO), as a cryoprotectant, was added, and then stored at -70
      degrees C for 1-30 days or at -196 degrees C for 1-84 days. The survival rate of
      stored cells was 64%-88%. During 6 days of storage with neuron culture medium,
      the survival rate of cells at 4 degrees C is over 50% each day, but, as time goes
      on, the count of the cells is getting less and less. The cells washed out DMSO
      after cryopreservation and the planting fresh cells can adhere to the wall of the
      culture bottle, grow, display various forms of neurons and gliacytes. From the
      above findings, it was suggested that: 1) The fetal human brain tissue, handled
      properly, can endure cryopreservation with 7% DMSO as a cryoprotective agent; 2)
      The storage time was related insignificantly to the survival rate of the tissues
      stored; 3) It is available for a short preservation at 4 degrees C; and 4) It is
      possible to set up a bank of fetal human brain tissue.

PMID- 8295261
TI  - Determination of most appropriate Nyquist velocity for applying hemispherical
      flow convergence equation to calculate flow rate using the transorifice pressure
      gradient: digital computer analysis of Doppler color flow convergence region.
AB  - Nyquist velocity and transorifice pressure gradient dramatically influence color
      aliasing shape and accuracy of simple hemispherical flow convergence equation for
      calculation of flow rate. The present in vitro study was performed to determine
      whether the value of Nyquist velocity, at which the shape of proximal isovelocity
      surface is best fit for a given shape assumption in different orifice size, and
      the flow rate may be a determinable and orifice size independent function of
      clinically measurable peak velocity or transorifice pressure gradient. Steady
      flow was driven through circular discrete orifices with diameter of 3.8 mm, 5.5
      mm and 10 mm and flow rate ranging from 2.88 L/min to 8.28 L/min. For every flow
      rate, Doppler color encoded M-mode images through the center of flow convergence
      region were transferred into the microcomputer in their original digital format.
      The continuous wave Doppler traces of maximal velocity through the orifice were
      performed for the calculation of pressure gradient. Direct numerical spatial
      velocity measure using color pixel intensity was obtained from the transferred
      color encoded M-mode images with computer software. The shape of isovelocity
      surface was determined by the ratio of calculated flow rate with hemispherical
      flow convergence equation to the actual flow rate. Both the flow rate and orifice
      size influence the position of the velocity profile curve. The shape of
      isovelocity surface is not constant and changes with the velocities used for the
      calculation of flow rates for a given flow rate and orifice size or pressure
      gradient and also changes with the flow rate or transorifice pressure gradients
      for a constant Nyquist velocity and orifice size.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8295262
TI  - Application of CDFI and portal system pressure measurement in the study of portal
      hypertension hemodynamics.
AB  - It has been discovered in portal system hemodynamics research using CDFI and
      pressure measurement, that among 40 portal hypertension patients the
      demonstrating rate of left gastric vein (LGV) was 77.5%, and all were
      hepatofugal. The demonstrating rates of spontaneous splenorenal vein shunt
      collaterals and of patency umbilical vein (UV) with blood signal were 85%, 12.5%
      respectively, and the thrombosis rate of portal system was 10%. Blood flow
      direction of main portal vein (MPV) in all patients was hepatopetal, and one case
      of superior mesenteric vein (SMV) and another one of splenic vein (SV) were
      hepatofugal. The patients with MPV thrombosis or portal system hepatofugal should
      be operated on by shunt. Shunt capacity of portal vein in gastroplenic region was
      34.07% on average. This demonstrated that devascularization was applicable.
      Internal diameter, blood capacity and time average velocity (TAV) of the left
      portal vein (LPV) and right portal vein (RPV) with portal hypertension were
      almost equal, their difference being not significant (P > 0.2). This should be a
      basis for the diagnosis of portal hypertension. Free portal pressure (FPP) and
      internal diameter, blood capacity and TAV of MPV, SV, SMV, LGV were not
      correlative with each other.

PMID- 8295263
TI  - Ultrasound diagnosis of effusion of the hip.
AB  - This paper reports on two prospective studies of ultrasound examination of the
      hip in 150 healthy subjects and 50 patients with hip joint diseases. The sagittal
      distance of the anterior recess of the hip was measured on the sonogram of the
      sagittal section. The normal value in adults, teenagers and children was 4.54 mm
      +/- 0.99 mm, 4.27 mm +/- 1.26 mm and 3.40 mm +/- 0.93 mm, respectively.
      Ultrasound examination of both hips in 50 patients with hip joint diseases showed
      that the sagittal distance of the anterior recess was significantly widened in
      the symptomatic side, and the mean value in the symptomatic side and normal side
      was 12.02 mm +/- 3.68 mm, and 4.12 mm +/- 1.15 mm, respectively. Ultrasound
      showed echo-free area in anterior recess in 42 hips, hypoecho and medium echo
      area in 8 hips. Of 50 patients undergoing plain radiography, 33 showed bony
      changes of the hip, and the remaining 17 no change whatever. The results obtained
      demonstrated that ultrasound can accurately detect effusion of the hip, what is
      more, it is easy to operate, inexpensive, noninvasive, convenient for follow-up
      and without radiation damage.

PMID- 8295264
TI  - Sonographic diagnosis of intramuscular hemangiomas.
AB  - This article reports 10 cases of intramuscular hemangiomas diagnosed by
      ultrasound. The results obtained demonstrated that the intramuscular hemangiomas
      were revealed sonographically as a spindle-shaped or ellipse-shaped mass with a
      mixed echo structure in the skeletal muscle, and usually with small
      calcifications. The solid parts of the tumor most commonly have a medium
      echogenicity, but few hyperechogenicity. The cavity or sinus containing blood has
      a hypoecho or echo-free structure.

PMID- 8295265
TI  - A comparative study of the influences of pulmonary arterial pressure and
      pulmonary capillary wedge pressure on impedance rheopneumogram in patients with
      three different diseases.
AB  - In the present study right heart catheterization and impedance rheopneumogram
      examinations were performed simultaneously on 21 patients suffering from
      congenital cardiovascular diseases with atrial or ventricular septal defect
      accompanied by the left to right shunt (CCD) and 17 patients suffering from
      rheumatic valvular disease with mitral stenosis (MS) in order to investigate the
      differences in the impedance rheopneumogram parameters between CCD patients and
      patients with chronic obstructive pulmonary disease (COPD) as well as between MS
      and COPD patients. The results showed that when patients with different diseases
      had the same level of pulmonary arterial pressure, CCD patients had significantly
      higher Hs than COPD patients, while MS patients had significantly higher Hd/Hs
      ratio than COPD patients and CCD patients. The linear regressional equation
      between Hd/Hs ratio and pulmonary capillary wedge pressure (PCWP) was as follows:
      PCWP (kPa) = 0.17 + 0.98 x Hd/Hs (kappa = 155, gamma = 0.422, p < 0.001). These
      results suggest that: (1) impedance rheopneumographic regressional equations with
      Hs as one of the major variables suitable for predicting secondary pulmonary
      hypertension in COPD patients are not suitable for use on CCD patients; (2) Hd/Hs
      ratio is useful in clinical work as an index for differential diagnosis between
      MS and Cor Pulmonale; and (3) PCWP can be roughly and noninvasively measured
      based on the measurement of impedance rheopneumogram parameter Hd/Hs.

PMID- 8295266
TI  - Noninvasive quantitative diagnosis of pulmonary artery hypertension with
      impedance rheopneumogram in patients with chronic obstructive pulmonary disease.
AB  - In order to evaluate the value of impedance rheopneumogram (IRP) in predicting
      pulmonary arterial pressure (PAP) and pulmonary arterial hypertension (PAH)
      noninvasively and quantitatively, 150 patients with chronic obstructive pulmonary
      disease (COPD) were examined by IRP and right heart catheterization
      simultaneously. It was found that some parameters derived from IRP correlated
      well with PAP, the strongest correlation being demonstrated by Q-B/B-Y ratio
      (gamma = 0.74, p < 0.001) and Hs (gamma = -0.56, P < 0.001). We made a multi
      stepwise regressional analysis and obtained an equation to predict PAP from IRP
      parameters: PAP (kPa) = [-2.26-5.05 x 1nHs + 27.02 x (Q-B/B-Y)] x 0.133 (gamma =
      0.78, P < 0.001). Other 30 COPD patients were selected to assess the
      effectiveness of the equation. We found that the sensitivity and specificity of
      the equation in identifying PAH were 83% and 93% respectively.

PMID- 8295267
TI  - Design and clinical evaluation of impedance pulmonary arterial pressure measuring
      instrument with computer.
AB  - Impedance pulmonary arterial pressure(PAP) measuring instrument with a
      microcomputer was designed and manufactured. It performs the functions of graphic
      analysis, logic judgment and mean pulmonary arterial pressure (PAP) measurement.
      Impedance information obtained by impedance PAP measuring instrument with a
      microcomputer was consistent with that by type HB-3COG apparatus. This new
      instrument has many advantages, such as reliability, saving of time and efforts
      as well as simplicity in operation.

PMID- 8295268
TI  - Evaluation of exercise-induced QRS amplitude changes (Athens score) and their
      clinical value.
AB  - The index of exercises-induced amplitude changes in a combination of Q, R and S
      waves, named Athens score, was tested in 213 patients, who underwent coronary
      angiography within 3 days of a maximal exercise test. Of the 155 cases with
      conclusive exercise test results, according to the coronary angiography document,
      23 (14.8%) were diagnosed as having no significant coronary artery disease (CAD);
      27 (17.4%) as 1-vessel disease; 28 (18.1%) as 2-vessel disease and 77 (49.7%) as
      3-vessel disease. The Athens score for them was 4.87 +/- 2.89, 0.02 +/- 3.35, 
      1.70 +/- 3.68, -1.75 +/- 3.98 respectively, F = 19.65, P < 0.01. An Athens score
      of 2 mm predicted CAD with sensitivity of 84.9% and specificity of 78.3% both
      being higher than those of ST segment depression (75.0% and 60.9%). It was
      concluded that the Athens score was a promising index for improving the
      efficiency of exercise test to predict CAD.

PMID- 8295269
TI  - Effects of captopril on platelet cytosolic free Ca2+ concentrations and on
      suppression of cell proliferation in culture.
AB  - In order to investigate the feasibility of angiotensin converting enzyme
      inhibitors (ACEIs) in preventing the development of atherosclerosis and
      restenosis after coronary angioplasty and to study their mechanisms, we measured
      the platelet cytosolic free Ca2+ concentration ([Ca2+]i) and observed the effects
      of captopril on platelet [Ca2+]i in rabbits and also observed the inhibitive
      action on fibroblast proliferation in culture. The results showed that resting
      platelet [Ca2+]i,ADP- or thrombin-stimulated platelet elevation amplitude after
      administration of captopril (12.5 mg, twice daily) for 15 days were significantly
      reduced in comparison with those before administration. And captopril also
      significantly inhibited fibroblast proliferation or reduced 3H-thymidine (3H-TdR)
      incorporation in culture in a dose-dependent manner. These findings suggest that
      ACEIs are promising drugs to reduce restenosis incidence after coronary
      angioplasty and to prevent atherosclerosis as well as provide a new explanation
      for their effects of suppressing cell proliferation.

PMID- 8295270
TI  - Diagnosis and therapy for primary hepatic carcinoma: transcatheter inferior
      phrenic arteriography and chemoembolization.
AB  - Transcatheter inferior phrenic arterial (IPA) and hepatic arteriography was
      performed on 38 patients with advanced primary hepatic carcinoma (PHC) with blood
      supplied by IPA and hepatic artery. 18 patients received single treatment with
      hepatic arterial infusion (HAI) or embolization (HAE) 20 received double
      treatment with IPA and hepatic arterial infusion or embolization. The results
      show that the double treatment is superior to the single one. The angiographic
      features and mechanism of parasitization of inferior phrenic arterial supply to
      PHC were also discussed.

PMID- 8295271
TI  - The catalytic stripping voltammetry of trace copper (II) at a chemically modified
      electrode on oxine containing carbon paste.
AB  - An oxine modified electrode is prepared on the basis of carbon paste. The process
      is rapid and simple. The catalytic stripping voltammetric characteristic of
      Cu(II) on the modified electrode was studied and the method has been applied to
      the determination of trace Cu(II), and there was good linear relationship between
      the concentration of Cu(II) and the peak height in the concentration range of 1.5
      x 10(-)-1.5 x 10(-6) mol/L for Cu(II). We have detected the copper content of
      human hair and blood with satisfactory results. Moreover, the reaction mechanism
      of the modified electrode was discussed. It was found that the improvement of
      sensitivity and selection of the modified electrode was dependent of the complex
      adsorbing property of the electrode surface and the sensitive catalytic hydrogen
      wave produce.

PMID- 8295272
TI  - Nation's blood supply dangerously low, banks call need for donors urgent.

PMID- 8295273
TI  - Realizing potential of MR coronary angiography may ease patients' test load and
      diagnosis costs.

PMID- 8295274
TI  - Once again, CABG vs PTCA--trial results today.

PMID- 8295275
TI  - From the Centers for Disease Control and Prevention. Vaccination coverage of 2
      year-old children--United States, 1991-1992.

PMID- 8295276
TI  - From the Centers for Disease Control and Prevention. HIV prevention practices of
      primary-care physicians--United States, 1992.

PMID- 8295277
TI  - From the Centers for Disease Control and Prevention. HIV transmission between two
      adolescent brothers with hemophilia.

PMID- 8295278
TI  - Survival after renal transplantation.

PMID- 8295279
TI  - Race and allocation of kidneys for transplantation.

PMID- 8295280
TI  - Race and allocation of kidneys for transplantation.

PMID- 8295281
TI  - What is necessary for proof? Is 95% sure unrealistic?

PMID- 8295282
TI  - Metered-dose inhalers: mouth open or closed?

PMID- 8295283
TI  - Reporting AIDS in New York City.

PMID- 8295284
TI  - Reporting AIDS in New York City.

PMID- 8295286
TI  - Coffee-associated osteoporosis offset by daily milk consumption. The Rancho
      Bernardo Study.
AB  - OBJECTIVE: To describe the association of lifetime intake of caffeinated coffee,
      in cup-years, to bone mineral density (BMD) of the hip and spine in
      postmenopausal women; and to determine the effect of regular milk intake on this
      association. DESIGN: Women from an established epidemiologic cohort had measures
      of BMD and gave a medical and behavioral history that included caffeinated coffee
      and daily milk intake between the ages of 12 and 18 years, 20 and 50 years, and
      50 years of age and older. SETTING: A community-based population of older women,
      Rancho Bernardo, Calif. PARTICIPANTS: All 980 postmenopausal women aged 50 to 98
      years (mean age, 72.7 years) who participated between 1988 and 1991. MAIN OUTCOME
      MEASURES: Bone density at the hip and lumbar spine measured by dual energy x-ray
      absorptiometry. MAIN RESULTS: There was a statistically significant graded
      association between increasing lifetime intake of caffeinated coffee and
      decreasing BMD at both the hip and spine, independent of age, obesity, parity,
      years since menopause, and the use of tobacco, alcohol, estrogen, thiazides, and
      calcium supplements. Bone density did not vary by lifetime coffee intake in women
      who reported drinking at least one glass of milk per day during most of their
      adult lives. CONCLUSIONS: Lifetime caffeinated coffee intake equivalent to two
      cups per day is associated with decreased bone density in older women who do not
      drink milk on a daily basis.

PMID- 8295285
TI  - Effect of captopril on progression to clinical proteinuria in patients with
      insulin-dependent diabetes mellitus and microalbuminuria. European
      Microalbuminuria Captopril Study Group.
AB  - OBJECTIVES: To study the effect of angiotensin converting enzyme inhibition on
      the rate of progression to clinical proteinuria and the rate of change of albumin
      excretion rates in patients with insulin-dependent diabetes mellitus and
      persistent microalbuminuria. DESIGN AND SETTING: Randomized, double-blind,
      placebo-controlled clinical trial of 2 years' duration at 12 hospital-based
      diabetes centers. PATIENTS: Ninety-two patients with insulin-dependent diabetes
      mellitus and persistent microalbuminuria but no hypertension. INTERVENTION: The
      patients were randomly allocated in blocks of two to receive either captopril, 50
      mg, or placebo twice per day. MEASUREMENTS: Albumin excretion rate, blood
      pressure, glycosylated hemoglobin level, and fructosamine level every 3 months;
      urinary urea nitrogen excretion every 6 months; and glomerular filtration rate
      every 12 months. RESULTS: Twelve patients receiving placebo and four receiving
      captopril progressed to clinical proteinuria, defined as an albumin excretion
      rate persistently greater than 200 micrograms/min and at least a 30% increase
      from baseline (P = .05). The probability of progression to clinical proteinuria
      was significantly reduced by captopril therapy (P = .03 by log-rank test).
      Albumin excretion rate rose from a geometric mean (95% confidence interval) of 52
      (39 to 68) to 76 (47 to 122) micrograms/min in the placebo group but fell from 52
      (41 to 65) to 41 (28 to 60) micrograms/min in the captopril group, a significant
      difference (P < .01). Mean blood pressure was similar at baseline in the two
      groups and remained unchanged in the placebo group but fell significantly, by 3
      to 7 mm Hg, in the captopril group. Glycosylated hemoglobin levels and glomerular
      filtration rate remained stable in the two groups. CONCLUSIONS: Captopril therapy
      significantly impeded progression to clinical proteinuria and prevented the
      increase in albumin excretion rate in nonhypertensive patients with insulin
      dependent diabetes mellitus and persistent microalbuminuria.

PMID- 8295287
TI  - A comparison of public attitudes toward autopsy, organ donation, and anatomic
      dissection. A Swedish survey.
AB  - OBJECTIVE: To evaluate people's reactions to procedures involving the dead body
      by comparing their attitudes toward autopsy, organ donation, and dissection.
      DESIGN: Survey, using a questionnaire with 24 items that address reactions toward
      autopsy, organ donation, and donation of the whole body, including religious and
      sociodemographic issues. PARTICIPANTS: An age-stratified, random sample of 1950
      individuals in Sweden, 18 to 75 years old. The response rate was 65%. RESULTS:
      Eighty-four percent reported acceptance of an autopsy for themselves and 80% for
      a close relative. Sixty-two percent were willing to donate their own organs and
      39% to donate the organs of a family member; 15% accepted donation of their whole
      body for dissection. Practically all who accepted dissection also were willing to
      donate their organs and to be autopsied; practically all who were willing to
      donate their organs also accepted autopsy. About 65% to 70% felt some discomfort
      at the thought of autopsy and organ donation. Women seemed more sensitive toward
      operations on the dead body than men. CONCLUSIONS: The rank order of medical
      procedures after death, based on the proportion of individuals positive toward
      the procedures, can be used to form a scale with autopsy and dissection at each
      end point and organ donation in the middle. This scale has the characteristics of
      a Guttman scale and can be looked on as a comfort-discomfort continuum regarding
      procedures involving the dead body.

PMID- 8295288
TI  - Remodeling of coronary arteries in human and nonhuman primates.
AB  - OBJECTIVE: To compare coronary artery remodeling (compensatory enlargement) in
      human and nonhuman primates. DESIGN: Coronary artery data were analyzed
      retrospectively for 416 nonhuman primates and 100 men and women. SETTING: The
      monkeys had been in experiments involving diet-induced coronary artery
      atherosclerosis. The human hearts were obtained from the North Carolina Baptist
      Hospital, Winston-Salem, and age greater than 25 years was the only criterion.
      PATIENTS AND OTHER PARTICIPANTS: The left anterior descending coronary arteries
      from 100 humans, 328 cynomolgus monkeys, and 88 male rhesus monkeys were used.
      INTERVENTIONS: None; this was a cross-sectional observational study. MAIN OUTCOME
      MEASURES: Coronary artery size, lumen area, and plaque size. In the humans, we
      also examined demographic characteristics (ethnicity, sex, and history of
      hypertension) and pathologic criteria (eccentricity or concentricity of plaque
      area). RESULTS: On average, lumen size remained unaffected by plaque size. Lumen
      size was variable and could not be predicted by traditional risk factors for
      coronary heart disease. However, lack of compensation (decreased lumen size as
      plaques enlarged) and history of coronary heart disease were significantly
      correlated. CONCLUSIONS: The similarity of remodeling in human and nonhuman
      primates suggests that the process has general biologic significance. Lack of
      remodelling may be a major determinant of whether a person with coronary artery
      atherosclerosis develops its complications.

PMID- 8295290
TI  - Gout without hyperuricemia.

PMID- 8295289
TI  - Ethical, behavioral, and social aspects of HIV vaccine trials in developing
      countries.
AB  - ISSUE: Several investigators are preparing to conduct efficacy trials of human
      immunodeficiency virus (HIV) vaccines in the developing world. Failure to
      adequately address the unique ethical, behavioral, and social issues that
      surround vaccine testing in that setting will jeopardize the success of these
      trials and future acquired immunodeficiency syndrome (AIDS) research in the host
      nation. DESCRIPTION OF THE PROJECT: Twelve investigators from Africa, Asia, North
      America, and South America reviewed previous experience with HIV trials in
      developing countries and explored potential solutions to these issues.
      CONCLUSIONS: Host country scientists, government officials, and media must be
      actively involved in all aspects of the trials. Minimum prerequisites for
      conducting the trial include the following: (1) researching vaccines active
      against developing world HIV isolates; (2) establishing and maintaining an
      adequate technological infrastructure; (3) assessing the feasibility of
      recruitment in countries where the existence of HIV may be denied; (4) designing
      methods to obtain informed consent from each individual subject, rather than
      exclusively from family members or community elders; (5) creating locally
      appropriate instruments to measure risk behavior; (6) identifying a behavioral
      intervention for placebo and treatment groups; (7) making available laboratory
      methods to distinguish between natural HIV infection and vaccine-induced
      seropositivity; and (8) guaranteeing that an effective vaccine is available free
      of charge to the placebo group and at affordable prices to other host country
      residents.

PMID- 8295291
TI  - Ocular toxoplasmosis. An old disease revisited.

PMID- 8295292
TI  - Rationing and the Americans with Disabilities Act.

PMID- 8295293
TI  - A statement on the generalist physician from the American Boards of Family
      Practice and Internal Medicine.

PMID- 8295294
TI  - Attitudes toward autopsy and organ donation in Sweden and the United States.

PMID- 8295295
TI  - Arteries too good to kill.

PMID- 8295296
TI  - Battlefield transfusions.

PMID- 8295297
TI  - Cost-effective preoperative laboratory testing.

PMID- 8295298
TI  - Will primary care lead the revolution?

PMID- 8295299
TI  - Environmental estrogenic agents area of concern.

PMID- 8295300
TI  - From the Institute of Medicine.

PMID- 8295301
TI  - From the Centers for Disease Control and Prevention. Drug-resistant Streptococcus
      pneumoniae--Kentucky and Tennessee, 1993.

PMID- 8295302
TI  - From the Centers for Disease Control an Prevention. Alcohol consumption and fetal
      alcohol syndrome awareness--Alaska, 1991 and 1993.

PMID- 8295303
TI  - From the Centers for Disease Control and Prevention. Jin bu huan toxicity in
      adults--Los Angeles, 1993.

PMID- 8295305
TI  - Physician payment: fee for time.

PMID- 8295304
TI  - From the Centers for Disease Control and Prevention. Adult blood lead
      epidemiology and surveillance--United States, third quarter, 1993.

PMID- 8295306
TI  - Physicians payment: fee for time.

PMID- 8295307
TI  - Physician payment: fee for time.

PMID- 8295308
TI  - Prehospital-initiated vs hospital-initiated thrombolytic therapy for myocardial
      infarction.

PMID- 8295309
TI  - LSD use among US high school students.

PMID- 8295310
TI  - Opiates for pain: patients' tolerance and society's intolerance.

PMID- 8295311
TI  - The pathogenesis of disseminated intravascular coagulation in sepsis.

PMID- 8295313
TI  - Lack of physician representation in framing policy on national health insurance-
      1938.

PMID- 8295312
TI  - Sushi syncope schusser gets wedeler's valve at Vail.

PMID- 8295314
TI  - Pulse oximetry during conscious sedation.

PMID- 8295315
TI  - Pulse oximetry during conscious sedation.

PMID- 8295316
TI  - Antibiotics for otitis media: a clarification.

PMID- 8295317
TI  - Decreasing cardiovascular disease and increasing cancer among whites in the
      United States from 1973 through 1987. Good news and bad news.
AB  - OBJECTIVE: Trends in cancer mortality, cardiovascular mortality, and cancer
      incidence are assessed among US whites to determine whether aging of the
      population and smoking patterns completely account for increased cancer rates
      from 1973 through 1987. DESIGN: For mortality, percentage changes in age-specific
      rates were calculated. For cancer incidence, trends in age-specific rates across
      time periods and birth cohorts were assessed for several sites. MAIN OUTCOME
      MEASURES: National US cardiovascular and cancer mortality rates and incidence
      rates for smoking-related cancer, breast cancer, and all other types of cancer in
      10% of the US population covered by the National Cancer Institute's Surveillance,
      Epidemiology, and End Results Program were analyzed. RESULTS: From 1973 through
      1987, cardiovascular mortality decreased 42% in the age group 0 to 54 years and
      decreased 33% in the age group 55 to 84 years; concurrently, cancer mortality
      decreased 17% in the younger group but increased 12% in the older group. By 1987,
      even though proportionally fewer people in the older age groups died, relatively
      more of them died of cancer. Men born in the 1940s had twice as much cancer as
      those born in 1888 through 1897 and more than twice as much cancer not linked to
      smoking; women born during this period had 50% and 30% more of these same
      cancers, respectively. Rates of smoking-related cancers in recent cohorts of
      women were five to six times greater than in those born in 1888 through 1897,
      while rates in men declined. Recent cohorts of women also had more than twice as
      much breast cancer as those born in 1888 through 1897. CONCLUSIONS: In recent US
      birth cohorts, our model found that increases in cancer have occurred that are
      not solely linked to aging of the population and smoking patterns. In light of
      these results and similar findings in Sweden, changes in carcinogenic hazards in
      addition to smoking are likely to have occurred and need to be studied further.

PMID- 8295318
TI  - The contributions of authors to multiauthored biomedical research papers.
AB  - OBJECTIVE: To determine the contributions of each author to multiauthored
      biomedical research papers. DESIGN: Mailed, self-administered survey.
      PARTICIPANTS: A total of 184 first authors from a consecutive sample of 200
      papers with four or more authors published in 10 leading biomedical journals.
      MAIN OUTCOME MEASURES: First authors' ratings of which authors had made
      substantial contributions to the following: initial conception of the study,
      design of the study, provision of needed resources, collection of data, analysis
      and interpretation of data, and writing the first draft of the paper or revising
      drafts for important intellectual content. RESULTS: The contributions of nonfirst
      authors varied greatly within and among papers. Even second and last authors-
      though they generally contributed more than other nonfirst authors--were markedly
      inconsistent in the extent and pattern of their contributions. Time spent on the
      research differed among authors by orders of magnitude. An appreciable number of
      authors made few or no substantial contributions to the research. CONCLUSIONS:
      The nature and extent of contributions of nonfirst authors to biomedical research
      reported in multiauthored papers cannot reliably be discerned (or discounted) by
      authorship or order of authors. The two core purposes of scientific authorship-
      to confer credit and denote responsibility for research--are not adequately being
      met by these authorship practices.

PMID- 8295319
TI  - Effect of changes in maternal age, parity, and birth weight distribution on
      primary cesarean delivery rates.
AB  - OBJECTIVE: To examine the effect of maternal age on cesarean delivery risk and to
      quantify the impact of demographic changes since 1970 on primary cesarean
      delivery rates. DESIGN: A cohort study. SETTING: Nonfederal short-stay hospitals
      in Washington State. PARTICIPANTS: All women who delivered live singletons with
      linked birth certificate and hospital discharge data from 1987 through 1990. MAIN
      OUTCOME MEASURES: Maternal age-, birth weight-, and parity-specific primary
      cesarean delivery rates, Mantel-Haenszel relative risk estimates for primary
      cesarean delivery by 5-year age category stratified by parity, and direct
      standardization of 1987 through 1990 primary cesarean rates to 1970 Washington
      State maternal age, birth weight, and parity distribution. RESULTS: Primary
      cesarean rates ranged from 3.2% for multiparous teenage women who delivered
      infants weighing 3500 g through 3999 g to 58.9% for primiparous women 40 years of
      age or older who delivered infants weighing 4000 g or more. After adjustment, the
      risk of cesarean delivery increased with each 5-year age increment among women 20
      years of age or older. We estimated that if the maternal age, parity, and birth
      weight distribution from 1987 through 1990 were identical to what existed in
      1970, Washington State's primary cesarean rate from 1987 through 1990 would have
      been 12.2%, compared with the observed rate of 14.8%. CONCLUSION: The lower
      adjusted primary cesarean rate reflects the demographic changes in the
      childbearing population, which may be responsible for 18% of the 1987 through
      1990 cesarean delivery rates. These findings suggest the importance of using
      maternal age-, birth weight-, and parity-specific primary cesarean delivery rates
      to compare populations and study temporal trends.

PMID- 8295320
TI  - Diarrheal morbidity during the first 2 years of life among HIV-infected infants.
AB  - OBJECTIVE: To determine the incidence, cause, and patterns of diarrhea during the
      first 2 years of life among infants infected perinatally with the human
      immunodeficiency virus (HIV). DESIGN: A cohort study in which infants were
      enrolled shortly after birth and followed up longitudinally using biweekly
      surveillance for the occurrence of diarrhea. Stool specimens collected at the
      onset of diarrhea were evaluated for enteropathogens. Infants who were infected
      with HIV were compared with uninfected infants. SUBJECTS: Infants born to HIV
      infected women at the University of Maryland Hospital, Baltimore, were recruited
      at 0 to 3 months of age. This analysis included 58 infants enrolled in the cohort
      and followed up at least 15 months (unless death intervened) whose HIV status was
      established (18 HIV-infected infants and 40 HIV-uninfected infants). MEASUREMENTS
      AND RESULTS: The overall incidence of diarrhea in HIV-infected infants was 3.2
      episodes per 12 child-months compared with 1.5 episodes per 12 child-months among
      HIV-uninfected infants (incidence density ratio, 2.2; P < .05). An enteropathogen
      was identified in stool specimens collected during 20% of diarrheal episodes
      occurring in HIV-infected infants and during 25% of diarrheal episodes occurring
      in HIV-uninfected infants. Episodes that persisted for 14 days or longer were
      significantly more common among HIV-infected infants. The peak incidence of
      diarrhea occurred at 0 to 5 months of age for HIV-infected infants compared with
      6 to 11 months for HIV-uninfected infants. Early onset of diarrhea (< 6 months
      old) in HIV-infected infants was associated with the later development of
      persistent episodes of diarrhea, and those with persistent episodes had more
      severe HIV infection, characterized by a significantly higher frequency of
      opportunistic infections and lower CD4+ T-lymphocyte counts by 1 year of age.
      CONCLUSION: Both acute and persistent episodes of diarrhea are major sources of
      morbidity in HIV-infected infants. Moreover, persistent diarrhea is a marker for
      rapid progression of HIV disease.

PMID- 8295321
TI  - Hypercholesterolemia in postmenopausal women. Metabolic defects and response to
      low-dose lovastatin.
AB  - OBJECTIVE: To determine the metabolic mechanisms underlying hypercholesterolemia
      in postmenopausal women and to determine whether a low dose of lovastatin will
      correct this abnormality. DESIGN: In the first part of the study, turnover rates
      of autologous low-density lipoprotein (LDL) were measured in hypercholesterolemic
      and control women. In the second part, hypercholesterolemic women participated in
      a placed-controlled, randomized, double-blind study using lovastatin as the
      therapeutic agent. SETTING: The General Clinical Research Center of the
      University of Texas Southwestern Medical Center, Dallas, utilizing inpatient and
      outpatient facilities, and the Veterans Affairs Medical Center, Dallas, Tex.
      PATIENTS: For the LDL turnover study, 26 postmenopausal women with moderate
      hypercholesterolemia (mean +/- SD LDL cholesterol, 4.78 +/- 0.59 mmol/L [185 +/-
      23 mg/dL]) and 13 postmenopausal women with normal levels of plasma lipids and
      lipoproteins (mean +/- SD LDL cholesterol, 3.31 +/- 0.39 mmol/L [128 +/- 15
      mg/dL]) were studied. Sixteen postmenopausal women participated in the drug
      study. INTERVENTIONS: In the drug study, patients received blindly both
      lovastatin (10 mg/d) and placebo. MAIN OUTCOME MEASURES: In the first study,
      kinetic parameters of LDL metabolism; in the second study, response in lipids and
      lipoproteins to lovastatin therapy. RESULTS: In the LDL turnover study, mean (+/-
      SD) input (production) rates for LDL apolipoprotein B (apo B) were similar for
      hypercholesterolemic women and control women (12.4 [+/- 3.2] mg/kg per day and
      11.1 [+/- 2.2] mg/kg per day, respectively). In contrast, mean (+/- SD)
      fractional catabolic rates for LDL apo B in hypercholesterolemic women (0.29 [+/-
      0.04] pools per day) were significantly lower than those in normolipidemic women
      (0.35 [+/- 0.03] pools per day). In the drug trial, lovastatin therapy reduced
      mean (+/- SD) total cholesterol and LDL cholesterol from 7.03 (+/- 1.16) mmol/L
      (272 [+/- 45] mg/dL) and 4.42 (+/- 0.80) mmol/L (171 [+/- 31] mg/dL,
      respectively, to 5.70 (+/- 1.03) mmol/L (221 [+/- 40] mg/dL) and 3.46 (+/- 0.85)
      mmol/L (134 [+/- 33] mg/dL). CONCLUSIONS: The turnover data suggest that
      hypercholesterolemia in post-menopausal women is primarily attributable to a
      reduced activity of LDL receptors. In accord, the hypercholesterolemia in these
      women was effectively lowered by low doses of lovastatin. Thus, a low dose of
      lovastatin appears highly effective for treatment of moderate
      hypercholesterolemia in most postmenopausal women, presumably because it reverses
      the reduction in LDL receptor activity associated with menopause.

PMID- 8295322
TI  - Improving health care for the poor. Lessons from the 1980s.

PMID- 8295323
TI  - How do we interpret the 'bad news' about cancer?

PMID- 8295324
TI  - Authorship! Authorship! Guests, ghosts, grafters, and the two-sided coin.

PMID- 8295325
TI  - [Analysis of chronic graft-versus-host disease in patients after bone marrow
      transplantation from HLA-identical siblings].
AB  - The incidence of chronic GVHD, involved organs, and outcome were evaluated in 59
      patients aged 15 years or more who survived for 2 months or more after HLA
      matched bone marrow transplantation. The incidence of chronic GVHD was 65.3%. The
      incidence was not correlated with the age at the time of transplantation,
      underlying disease, or the method to prevent GVHD (group treated with MTX alone
      and CSP-treated group). Concerning the degree of organ involvement, the CSP
      treated group more frequently showed slight involvement and, especially a
      significantly lower incidence of dryness of the eyeballs. According to organs,
      the oral cavity was most frequently involved (87%), followed in order by the
      liver (74%), skin (52%), and the eyes (30%). The oral cavity alone was involved
      in 6 patients, and the outcome was generally good. The outcome of multi-organ
      involvement of chronic GVHD was poor, and the major causes of death were
      interstitial pneumonia and sepsis. Even of patients who did not develop chronic
      GVHD, 25% showed dryness of the eyeballs and oral cavity. Biopsy and careful
      observation of the clinical course are needed for diagnosing GVHD.

PMID- 8295326
TI  - [Effect of THP-CVP regimen for elderly patients with malignant lymphoma].
AB  - Between April 1990 and June 1992, a multicenter clinical trial of chemotherapy
      regimens was performed with patients, aged 65 years or more, suffering from
      malignant lymphoma. The total number of patients was 38 included 30 initial cases
      (median age: 72) and 8 relapsed cases (79). The chemotherapy regimen,
      administered every 3 weeks, included pirarubicin (30 mg/m2; day 1),
      cyclophosphamide (500 mg/m2; day 1), vindesine (1.5 mg/m2; day 1), and
      prednisolone (40 mg/m2; days 1-5) for the initial cases, and etoposide (100
      mg/m2; days 1-5) in addition for relapse cases. The complete response and partial
      response rates were 50.0% and 40.0% in initial cases, respectively, and 50.0% and
      0% in relapsed cases, respectively. The 50% survival period was 25.9 months in
      initial cases and 18.0 months in relapse cases. There were no serious side
      effects related to the regimens. Performance status deteriorated in only one case
      after chemotherapy. We concluded that the chemotherapy regimens were useful and
      safe for elderly patients with malignant lymphoma.

PMID- 8295327
TI  - [Clinical study of GM-CSF in patients with aplastic anemia and myelodysplastic
      syndrome. (CSF39-300 Study Group)].
AB  - We administered granulocyte-macrophage colony stimulating factor (GM-CSF) to
      patients with aplastic anemia and myelodysplastic syndrome (MDS), as a phase III
      trial. The GM-CSF was given by 3 hrs intravenous drip infusion daily for at least
      fourteen days. Twenty-five patients with aplastic anemia and nineteen patients
      with MDS were evaluable for efficacy. Peripheral blood granulocyte counts,
      especially neutrophil counts and eosinophil counts, increased markedly by the
      administration of GM-CSF in each disease. Fifteen patients with MDS and nineteen
      patients with aplastic anemia responded to the GM-CSF. Dose-related increase of
      granulocytes were seen in patients with MDS, but no relation was seen in patients
      with aplastic anemia. Adverse effects were observed in some patients and flu-like
      syndrome including fever, general fatigue and anorexia were seen most commonly
      but were transient. Our results showed that GM-CSF is a potent stimulator of
      hematopoiesis in patients with aplastic anemia and MDS.

PMID- 8295328
TI  - [HTLV-I negative adult T cell leukemia; a case report of acute type].
AB  - We described a case of adult T cell leukemia (ATL) not associated with human T
      cell leukemia virus type I (HTLV-I), a clinical entity that was first reported by
      Shimoyama et al. A 79-year-old male was admitted with anorexia and fever in
      October, 1989. Physical examination revealed marked hepatosplenomegaly and
      superficial lymphadenopathies. Hematological examination revealed marked
      leukocytosis (136,300/microliters) with abnormal lymphoid cells showing highly
      lobulated nuclei. Hypercalcemia (11.2 mg/dl) and elevation of lactic
      dehydrogenase were also recognized. Surface marker analysis showed that the
      abnormal lymphoid cells in the peripheral blood were positive for CD2 and CD4 but
      negative for CD8. Southern blot analysis of the DNA from peripheral blood
      leukemic cells revealed monoclonal rearrangement of T-cell receptor beta-chain
      gene. The clinical and hematological findings of the patient were compatible with
      those of acute type ATL, however, serum anti-HTLV-I antibody was negative and
      HTLV-I proviral DNA was not detected in the leukemic cells by Southern blot
      analysis. Furthermore, the polymerase chain reaction showed no integration of the
      HTLV-I proviral DNA in the leukemic cells.

PMID- 8295329
TI  - [Extramedullary blast crisis of mixed precursor T lymphoblastic and myeloblastic
      features in a patient with chronic myelogenous leukemia successfully treated with
      low-dose oral etoposide].
AB  - A 47-year-old man presented with fever, cough and chest pain in January, 1989. He
      was found to have mediastinal tumor and generalized lymphadenopathy. Peripheral
      blood and bone marrow findings were typical for the chronic phase of chronic
      myelogenous leukemia (CML). Although the histological findings of a cervical
      lymph node were indistinguishable from those of malignant lymphoma, cytogenetic
      studies of the lymph node cells showed positive Ph1 chromosome and rearrangement
      of the bcr gene as well as bone marrow cells. Double fluorescence analysis of
      lymph node cells demonstrated co-existence of CD5, CD7 and CD33 positive cells
      and of cells sharing both CD5 or CD7 and CD33 antigens. These findings suggest
      that tumor cells originate from the stage at which the differentiation pathways
      of hematopoietic stem cells branch into precursor T and myeloid cells. Various
      combination chemotherapies had only partial effects on lymph node swelling.
      Chronic daily administration of low dose etoposide was very effective to control
      both lymphadenopathy and leukocytosis and the patient remained well for over 2
      years until July, 1991 when hematological myeloid blast crisis developed. He died
      of pneumonia in October, 1991. This is a rare case of CML with extramedullary
      mixed crisis which survived for a long time.

PMID- 8295330
TI  - [Null-cell non-Hodgkin's lymphoma presenting with a mass in the chest wall after
      tuberculous pyothorax].
AB  - A 59-year-old male, who was treated with artificial pneumothorax for pulmonary
      tuberculosis 42 years previously, presented with a painful mass in the left
      lateral chest wall and lymph node swelling in the left neck. A chest CT-scan
      revealed a tumor shadow extending from the outer chest wall to the pleural cavity
      containing pus surrounded by calcified pleura. 67Ga scintigraphy showed
      accumulation of the radionuclide in the left lateral chest and left neck. Biopsy
      specimen obtained from both the chest tumor and cervical lymph node revealed
      diffuse large cell lymphoma. Immunostaining failed to demonstrate CD1, CD3, CD4,
      CD8, CD13, CD20, immunoglobulin, alpha, gamma, mu, delta, kappa and lambda
      chains, indicating null cell characteristics. Chemotherapy consisting of
      cyclophosphamide, doxorubicin, vincristine, prednisolone and bleomycin and
      irradiation resulted in a temporary decrease of the tumor and lymph nodes, but
      the patient died of pneumonia 14 months after the onset of disease. Since the
      levels of serum lactate dehydrogenase and immunosuppressive acidic protein varied
      in parallel to the disease activity, they appeared to be useful for the
      assessment of therapeutic effects during the clinical course. Approximately 100
      cases of non-Hodgkin's lymphoma developing after tuberculous pyothorax have been
      reported in this country, among which the incidence of null cell type is
      exceedingly rare.

PMID- 8295331
TI  - [Two cases of acute myelogenous leukemia with Bacillus cereus bacteremia
      resulting in fatal intracranial hemorrhage].
AB  - This manuscript reports Bacillus cereus sepsis in two cases with acute
      myelogenous leukemia (AML) who suffered complications of fatal intracranial
      hemorrhage during remission induction therapy. The first case was 43-year-old
      male with AML (M0) receiving first consolidation chemotherapy who developed
      sudden diarrhea, abdominal pain and spiking fever. Two days later, he died of
      intracranial hemorrhage. The second case was 15-year-old male with AML (M5b) who
      was receiving first induction chemotherapy. He developed headache and vomiting
      following spiking fever and diarrhea. He died of subarachnoid hemorrhage the next
      day. In both cases, Bacillus cereus was isolated from blood culture. Fatal
      intracranial hemorrhage due to severe bleeding tendency caused rapid to death in
      both cases. These bleeding tendencies might have been induced by B. cereus
      sepsis. In addition, we should not overlook B. cereus as contamination, but
      rather consider it as a potential pathogen, when isolated from blood culture.

PMID- 8295332
TI  - [Hemophagocytic syndrome with high level of interferon-gamma in the advanced
      stage].
AB  - Serum cytokines, lymphocyte subsets of peripheral blood and natural killer cell
      activity were serially assayed in a 3-year-old girl with hemophagocytic syndrome.
      Laboratory findings showed pancytopenia, increased levels of transaminases and
      hyperferritinemia and proliferation of histiocytes in bone marrow and pleural
      effusion. The administration of prednisolone resulted in a temporary improvement
      followed by a further exacerbation. The patient died in spite of the treatment
      with VP-16 and THP-adriamycin. Serum interferon-gamma (IFN-gamma) markedly
      increased in active phases. TNF-alpha, IL-1 beta and GM-CSF concentrations were
      normal or slightly elevated. The CD4/8 ratio of peripheral lymphocytes and
      natural killer cell activity also fluctuated according to clinical stage. These
      results suggested that IFN-gamma was the most important cytokine to activate
      histiocytes in this case.

PMID- 8295333
TI  - [Essential thrombocythemia in pregnancy].
AB  - A 30-year-old woman was admitted to our hospital because of thrombocythemia
      during pregnancy. Her leukocyte count was 10,000/microliters, Hb was 11.7 g/dl,
      and platelet count 181.9 x 10(4)/microliter. Bone marrow aspirate showed an
      increase in megakaryocytes (255/microliters). Both Ph1 chromosome and bcr
      rearrangement were negative. She was diagnosed as having essential
      thrombocythemia (ET) with pregnancy, and was treated with aspirin (150 mg/day).
      Her pregnancy was uneventful, but she was readmitted because of overterm
      pregnancy. A caesarean section was performed, and a healthy male infant weighing
      3,672 g was delivered, with a platelet count of 25.5 x 10(4)/microliter. However,
      the uterine was atonic, and atonic hemorrhage occurred. Supravaginal hysterectomy
      was performed. Subsequently, intrabdominal gross hemorrhage occurred, but the
      bleeding was halved by platelet transfusion. Microscopic examination showed
      uterine infarction. We suggest that platelet count should be reduced by means of
      plateletpheresis or interferon-alpha throughout pregnancy with ET.

PMID- 8295334
TI  - [Unrelated match bone marrow transplantation for severe aplastic anemia].
AB  - The results of unrelated bone marrow transplantation (BMT) is poor because of the
      rejection of bone marrow graft and graft versus host disease (GVHD). However, the
      rate of rejection has been reported to be decreased by intensive immuno
      suppressive preconditioning regimens combined with total body irradiation (TBI).
      We report a case of an 18-year-old male with severe aplastic anemia who received
      a matched BMT from an unrelated donor. The pre-conditioning regimen included
      cyclophosphamide (50mg/kg) for 4 days, total lymphoid irradiation (TLI: 6Gy) and
      TBI (5Gy). GVHD (grade 1), hemorrhage cystitis and varicella occurred after BMT
      but were cured. His performance status is now 100% on the Karnofsky score at 10
      months after BMT.

PMID- 8295335
TI  - [A fatal case of a hepatitis B virus carrier with fulminant hepatic failure after
      cytotoxic chemotherapy for malignant lymphoma].
AB  - A 48-year-old woman with malignant lymphoma, who was diagnosed as a hepatitis B
      virus (HBV) carrier because of positive HBs antigen, was admitted to Chiba Cancer
      Center Hospital. Complete remission was achieved by two courses of combination
      chemotherapy, but fulminant hepatitis developed after withdrawal of chemotherapy
      and she died of hepatic failure. Retrospective analysis of viral DNA disclosed a
      mutation in the precore region of HBV-DNA in her serum. We consider that the
      precoremutant virus was associated with the pathogenesis of severe hepatic
      failure after withdrawal of cytotoxic chemotherapy.

PMID- 8295336
TI  - [Pathophysiology and diagnosis of malignant neoplastic disorders of the
      hematopoietic system].
AB  - The Pathophysiological analysis of hematopoietic tumors has advanced markedly
      owing to the progress in the fields of histomorphology, biochemistry,
      hematopoietic stem cells including cytokines, cell surface markers, cytogenetics,
      and molecular biology. This progress has led to the establishment of many new
      disease concepts and has almost completely changed the recognition of
      hematopoietic tumors. These basic studies have also supported the development of
      effective therapy of hematopoietic tumors. Of course, this progress has been
      reflected in the techniques and knowledge in routine laboratory evaluation.

PMID- 8295337
TI  - [Hematological analysis of leukemic diseases using an automated hematology
      analyzer].
AB  - Owing to recent technical developments in automated hematology analyzers,
      identification of 5-part differential counts in white blood cells and also of
      abnormal leukocytes has become possible. Blood specimens from 200 patients with
      leukemic hematologic conditions were processed through a Coulter STKS which gives
      a favorable white cell differential count utilizing the following parameters:
      volumetric impedance (V), electric conductivity/cell volume (C), and a
      monochromatic laser beam which provides collectively white cell scatterplot (S).
      To analyze the presented figures of a pathologic scatterplot (SP) on the visual
      display unit, the standard scale derived from 220 normal SP patterns which was
      composed of four kinds of cell SP scales (neutrophil: N, monocyte: Mo,
      eosinophil: Eo, lymphocyte: Ly) was applied. Leukemic SP figures were variable
      depending upon both the type of FAB classification and their therapeutic
      processes. SP forms of M0-blasts were semi-round and located in the central area
      surrounded by N-, Mo-, and Ly-SP scale. Blast SP of M1 and M2 was shown as a
      developing process to the SP field containing immature myeloid cells extending
      from the central area. It was reasonable that immature neutrophilic SP expression
      was obtained in M3 and Ph1 positive CML. However, the SP of M3v and Ph1 negative
      CML showed myelomonocytic features as CMMoL does. Typical myelomonocytic SP
      patterns were obtained in M4 patients. SP figures of MDS were characterized by
      deformability, dislocation and another abnormality, and these changes, especially
      in lymphocytes are very useful for diagnosis of MDS. Therefore, the FAB subtype
      of AML including MDS and CML could be distinguished from each other on the basis
      of SP pattern. In lymphoproliferative disorders, limited conductivity in ALL-SP
      was characteristic, while irregular and deformed SP was peculiar in leukemic
      malignant lymphoma. It would be a valuable process to analyze the SP pattern
      obtained from an automated hematology analyzer for identification of leukemic
      diseases.

PMID- 8295338
TI  - [Marker analysis of leukemic cells].
AB  - Leukemic cells as well as normal blood cells possess several antigens on their
      cell surfaces. By detecting these cell-type-specific molecules using monoclonal
      antibodies and flow cytometry, these immunological methods can be applied to both
      clinical and basic tumor studies. The analysis of cell surface markers has been
      widely applied in the diagnosis and the management of hematological disorders
      such as leukemias and lymphomas and it has become to be utilized as the routine
      work in many laboratories. Such analysis has been particularly useful in
      lymphocytic leukemias due to the ability of this method to classify lymphocyte
      subtypes, as well as specify their developmental origin. Importance is that, with
      this information, it is possible to determine expected clinical prognosis, to
      recommend treatment options and to judge treatment efficacy. In addition, two- or
      three-color staining for cell surface markers using fluorescein isothiocyanate
      (FITC)-, phycoerythrin (PE)- and/or peridinin chlorophyll protein (per CP)-
      conjugated monoclonal antibodies can provide further detailed and more precise
      analysis.

PMID- 8295339
TI  - [Molecular implication of Ph positive leukemias: treatment with alpha-interferon
      in Ph positive acute leukemia].
AB  - Patients with Philadelphia chromosome-positive acute leukemia (Ph + AL) were
      treated with natural interferon-alpha (IFN-alpha) after entering complete
      remission. In this study, subsequent cytogenetic analysis during complete
      remission in Ph + AL patients with major-BCR rearrangement revealed that the
      percentage of bone marrow cells with the Ph chromosome increased, while the bone
      marrow maintained a remission status. This cytogenetic-hematologic discrepancy
      led us to consider that the Ph + metaphases might be derived from cells with a
      non-lymphoid lineage rather than residual leukemic lymphoblasts. After
      administration of IFN-alpha, the percentage of bone marrow cells with a Ph
      chromosome decreased. Although this study is on going and we do not yet have the
      final results, treatment of IFN-alpha should be attempted on more patients with
      such a genetic abnormality.

PMID- 8295340
TI  - [Vitamin B12 and transcobalamin in chronic myeloproliferative disorders].
AB  - Although vitamin B12 is an essential coenzyme for DNA synthesis, humans, like
      other mammals, are incapable of synthesizing it. The role of intrinsic factor
      (IF) in B12 absorption is widely known, but, in fact there exists a much more
      intricate and complex mechanism for the effective assimilation of this important
      trace element in humans. B12 binding proteins play important roles in all stages
      of vitamin B12 metabolism. They are involved not only in its absorption, but also
      in its transport in serum, uptake to cells, storage in organs, enterohepatic
      circulation, and elimination of its analogues. Besides IF, well-known as a
      vitamin B12 binding protein found in gastric juice, there are other kinds of
      binding proteins found in human serum which are composed to transcobalamin (TC)
      I, II and III. Elevation of the vitamin B12 level in chronic myelogenous leukemia
      was first reported in the 1950s. Since then, B12 elevation has been found to
      occur in other kinds of chronic myeloproliferative disorders (CMPDs) as well and
      to be caused by an increase of serum TC. In CMPDs, either TCI or TCIII increases,
      but, the degree of elevation and the type of TC involved differs for each
      disorder. This article describes the changes in TC of CMPD patients. With the
      induction of the developed radioimmunoassay for R-type B12 binding protein, many
      cases have been examined. In addition, detailed qualitative analysis using DEAE
      cellulose column chromatography has been included for conditions not previously
      reported.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295341
TI  - [Detection of HIV-1 proviral DNA in peripheral leukocytes by AMPLICOR HIV-1 test
      kit].
AB  - AMPLICOR HIV-1 test kits, which had been developed as an HIV-1 provirus detection
      test by PCR method, have been evaluated for its clinical diagnostic application.
      Sixty-six of HIV-1 antibody positive and 67 of HIV-1 antibody negative blood
      samples derived from hemophiliacs, who had received blood products, have been
      tested by AMPLICOR HIV-1. All of the results from AMPLICOR HIV-1 were consistent
      with those from antibody test and clinical aspects. Thirty-nine of HIV-1 antibody
      positive samples have been tested by AMPLICOR HIV-1 and virus isolation (culture
      method). Twelve of 39 (30.8%) were positive by virus isolation, and 39 of 39
      (100%) were positive by AMPLICOR HIV-1. Two of new born infants from HIV-1 sero
      positive mothers were tested by AMPLICOR HIV-1, and the result suggested that the
      kit would be useful for diagnosis of infants from sero-positive mothers. Based on
      these studies, AMPLICOR HIV-1 is considered as useful clinical diagnostic for HIV
      1 proviral DNA detection.

PMID- 8295342
TI  - [The detection of Helicobacter pylori by PCR in gastric diseases].
AB  - There are several methods for detecting Helicobacter pylori (H.pylori) infection,
      but all of them have both advantage and disadvantage. In this study, we
      investigated the usefulness of PCR as a routine screening method for H.pylori
      infection. We used PCR by identification of bacterial specific 16SrRNA gene. This
      test was performed on gastric biopsy specimens and gastric aspirate and stomatic
      mucus from 23 patients in gastric disease, and compared the sensitivity with
      other methods such as urease and culture test. We could detect H.pylori above
      10(3)/ml of bacterial volume by PCR and H.pylori were positive in 96% of all
      gastric biopsy specimens. PCR was most sensitive and specific method for
      detecting H.pylori. Thus, PCR was considered to have a possibility of becoming an
      accurate routine screening method of H.pylori infection.

PMID- 8295343
TI  - [Comparison between ELISA and culture method for detection of Helicobacter
      pylori].
AB  - Detection of Helicobacter pylori (H. pylori) by ELISA was compared with that by
      the culture method in 115 patients with gastroduodenal diseases. Both the
      sensitivity and specificity were more than 85% for patients with histological
      gastritis with neutrophil infiltration. This indicated that the detection of H.
      pylori by ELISA is useful for the diagnosis of H. pylori-related gastritis.
      Although the sensitivity between the ELISA and culture method was 85%, the
      specificity was 58.8%. The false negative detection may have been caused by a
      sampling error during the endoscopic biopsy.

PMID- 8295344
TI  - [Evaluation of type IV collagen in patients with various thyroid disease].
AB  - Serum level of type IV collagen was measured in 104 patients with various thyroid
      disease, and the relationship between its level and thyroid hormone level was
      examined. The type IV collagen was measured by the method of one step sandwich
      enzyme immunoassay (EIA) using two distinct monoclonal antibodies recognized
      triple-helical (TH) domain and 7-S domain, respectively. The serum level of type
      IV collagen was significantly high in the hyperthyroid patients compared with
      that in normal controls, and a significant positive correlation was found between
      its value and thyroid hormone levels (T3, T4, FT3, FT4). The elevated level of
      type IV collagen in hyperthyroid patients was decreased to normal level, when
      they became to euthyroid after antithyroid drug therapy for hyperthyroidism. The
      serum level of type IV collagen was in normal range in hypothyroid patients, but
      the value was increased to high normal range after T4-replacement therapy for
      hypothyroidism. This evidence indicates that the serum level of type IV collagen
      is closely related to thyroid hormone level in patient with various thyroid
      disease. Type IV collagen concentration might be one of the useful variables for
      evaluating the thyroid function, although its mechanism is not elucidated.

PMID- 8295345
TI  - [Effect of theophylline on the thyroid function in healthy subjects: comparison
      between the short- and long-term medication].
AB  - Effect of theophylline on the thyroid function was studied in 9 healthy subjects.
      Theophylline (200mg) was taken two times (AM8:00, PM10:00) and blood was
      collected two times (AM9:00, PM4:00) a day for five days. Five of these 9
      subjects took same dose two times (AM8:00, PM10:00) a day and blood was collected
      once (AM9:00) a week for four weeks. In short-term medication, serum free
      thyroxine (FT4) increased significantly (1.19 +/- 0.19 ng/dl, before medication)
      in 4th day AM (1.29 +/- 0.14 ng/dl, p < 0.05), in 4th day PM (1.30 +/- 0.12
      ng/dl, p < 0.05) and in 5th day AM (1.30 +/- 0.16 ng/dl, p < 0.05). Serum free
      triiodothyronine (FT3) increased significantly (3.9 +/- 0.36 pg/ml, before
      medication) in 4th day AM (4.3 +/- 0.66 pg/ml, p < 0.05) and in 5th day AM (4.3
      +/- 0.61 pg/ml, p < 0.05). Serum thyroid stimulating activity (TSA), which was
      measured as an increase in cAMP in FRTL-5 cells, increased significantly (116.5
      +/- 49.5%, before medication) in 1st day PM (152.3 +/- 60.0%, p < 0.05), in 2nd
      day PM (192.6 +/- 86.7%, p < 0.05), in 3rd day PM (208.5 +/- 94.1%, p < 0.05) and
      in 4th day AM (183.5 +/- 80.1%, p < 0.05). In contrast, serum FT4, FT3, TSH, and
      TSA did not increase significantly in long-term medication.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8295346
TI  - [Fluctuation of plasma levels of fibrinogen degradation products, fibrin
      degradation products and total fibrin/fibrinogen degradation products in patients
      with DIC].
AB  - Ten patients with disseminated intravascular coagulation syndrome (DIC) were
      analyzed using three enzyme linked immunosorbent assays (ORGANON TEKNIKA,
      Belgium) for fibrin degradation products (FbDP), fibrinogen degradation products
      (FgDP) and total fibrin/fibrinogen degradation products (TDP). A significant
      elevation in each parameter and a significant depression of FgDP/FbDP (g/b) ratio
      were observed in the patients in early stage of DIC, comparing with normal
      individuals (p < 0.001 and p < 0.01). These results suggested that both
      fibrinolysis and fibrinogenolysis were marked accelerated, with a superiority in
      fibrinolysis in those patients. The levels of these parameters decreased and the
      g/b ratio increased with the passage of the clinical courses in five patients who
      were improved. Although in five deteriorated cases, the levels were kept high and
      their g/b ratio showed low continuously. These findings suggested that separated
      monitoring of fibrinolysis or fibrinogenolysis was useful to study patients with
      DIC and g/b ratio could be regarded as a helpful indication of therapeutic
      effects.

PMID- 8295347
TI  - [Alcohol-related high blood pressure, and erythrocyte Na+/K(+)-ATPase activity,
      sodium and potassium concentrations].
AB  - Erythrocyte Na+/K(+)-ATPase activity (Ery-ATPase) and intra-erythrocyte sodium
      and potassium concentrations (Ery-Na, Ery-K) were determined in 83 men aged
      between 36 and 60 years. Volumes of alcohol consumed during the preceding one
      week (Alc) correlated significantly with blood pressure (BP), but not correlated
      with Ery-ATPase and Ery-K. Ery-Na showed a week inverse correlation with Alc, but
      the partial correlation after adjusting Ery-ATPase was not significant.
      Therefore, elevations of BP found in alcohol consumers are not related to changes
      in the cell-membrane Na+/K(+)-ATPase activity and intracellular Na and K
      concentrations. Ery-ATPase showed a borderline significant positive correlation
      with diastolic BP (0.05 < or = p < 0.10), independently of age, body mass index
      and Alc. The significance of the weak association in the pathogenesis of
      hypertension remains unclear.

PMID- 8295348
TI  - [Evaluation of serum enzyme levels considering biological half lives of enzymes-
      alteration of lactate dehydrogenase isoenzyme pattern due to computer
      simulation].
AB  - The rapid clearance of certain releasing enzymes from blood stream may modify
      their usefulness as markers of disease. Serum LD isoenzyme patterns are often
      quite different from those in the affected tissues. Such differences result from
      differences in the biological half lives of the individual isoenzyme. In order to
      reveal such phenomena, we applied the one-compartment model to simulate the time
      dependent changes in the serum LD isoenzyme patterns as a most simple model. When
      we simulated leukemic cells as an affected origin, LD isoenzyme patterns obtained
      at a stage of clinical deterioration or active stage, were characterized by a
      high proportion of LD-2, LD-3 and LD-4, and resembled those of the original
      leukemic cells. In general, strong similarities in alterations of LD isoenzyme
      patterns were obtained between the clinical observed time course and simulated
      time course. These changes in LD isoenzyme patterns are practically observed in
      the cases of leukemia, lymphoma, and so on. If the original organs are identical,
      then it is change of disease stage that is responsible for modification of
      variable LD isoenzyme patterns. Such phenomena must therefore be noted--in doing
      so, we shall be able to estimate the origin of enzyme release, disease stage, and
      prognosis.

PMID- 8295349
TI  - [Analysis of the variations of clinical test data on fasting therapy using fuzzy
      similarity dendrogram].
AB  - The values of assayed various chemical constituents in serum were varied on
      fasting therapy. The correlationship of the change among such constituents was
      investigated by drowning the dendrogram using fuzzy similarity relations. Normal
      and severe obese subjects were respectively selected from the fasting patients at
      Hyogo prefectural KENKO DOJO, and in contrast non-fasting healthy people were
      also selected. Fasting was practice under the conditions of 300 Kcal per day for
      7 days, and then refeeding was enforced for 7 days after fasting. 21 Items of
      biochemical tests were used for this analysis, and dendrogram was drown by
      Otake's method. On the dendrogram of reference, the significant correlations
      between AST and ALT, Total Protein and Cholinesterase, Sodium and Potassium were
      found. The dendrogram of fasting period of normal group showed the simple
      patterns, and unique correlations were drawn on the dendrogram of refeeding
      period of normal group. The dendrogram of severe obese group of refeeding period
      showed more simple patterns than fasting period.

PMID- 8295351
TI  - [Characteristics and management of hypertension in the elderly].

PMID- 8295350
TI  - [The population history of the Japanese].
AB  - This paper introduces a "dual structure model" that explains the population
      history of the Japanese population including the Okinawa islanders (Ryukyus) and
      Ainu under a single hypothesis. The model assumes that the first occupants of the
      Japanese Archipelago came from somewhere in Southeast Asia in the Upper
      Palaeolithic age and gave rise to the people in the Neolithic Jomon age, or
      Jomonese; then the second wave of migration from North Asia took place in and
      after the Aeneolithic Yayoi age; and the populations of both lineages gradually
      mixed with each other. The "dual structure model" also assumes that the
      population intermixture is still continuing and the dual structure of the
      Japanese population is maintained even today. Thus, several regional differences
      such as those between eastern and western Japan in physical as well as cultural
      characteristics can be explained by the rates of intermixture that vary from
      region to region. In general, this model agrees well not only with physical and
      cultural evidence but also with non-human evidence revealed by man's symbiotic
      animals such as Japanese dogs and mice. At the same time, the model provides a
      reasonable way of explanation in regard to affinities and relationships among the
      Japanese main islanders, Ryukyus and Ainu.

PMID- 8295352
TI  - [Comparative studies on complications occurring during and after surgery in
      elderly patients with and without cardiovascular disorders].
AB  - Comparative studies of the differences in elderly patients with and without
      cardiovascular disorders were made in regard to complications occurring during
      and after operation. The subjects included 38 patients (6 men and 32 women) aged
      70 to 99 years (mean: 84 years) at Nagoya City Kouseiin Geriatric Hospital who
      had orthopedic surgery under general anesthesia, between March 1990 and October
      1992. Diseases identified in these subjects were sequelae of cerebrovascular
      disease (38 subjects), heart disease (22 subjects), hypertension (9 subjects),
      senile dementia (6 subjects), Parkinson's disease (5 subjects), malignant disease
      (3 subjects) and diabetes mellitus (2 subjects). They were initially divided into
      2 groups according to ultrasonic cardiography: a normal group comprising 20
      patients without cardiovascular abnormalities, and a disorder group comprising 18
      patients with reduction of left ventricule function, left ventricular hypertrophy
      and/or valvular disease (more than moderate). All subjects were examined with
      regard to age, weight, the nutrition index proposed by Onodera, activity of daily
      living (ADL), cardiac output, left ventricular ejection fraction, serum level of
      BUN and albumin etc. Moreover, the disorder group subjects were divided into 2
      groups according to the presence or absence of heart failure occurring after
      surgery. In addition to the above-mentioned, we also studied the duration of
      surgery and anesthesia, and water balance during and after surgery. Results
      showed that the ADL and nutrition index in the disorder group were lower compared
      to the normal group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295353
TI  - [Comprehensive functional assessment of the elderly in institutions, particularly
      in terms of social life].
AB  - The purpose of this study was to clarify aspects of social life in a
      comprehensive functional assessment of 160 elderly subjects, over 60 years of
      age, in institutions for the elderly. Five items were assessed: economic
      conditions, marital status, family conditions, family relationships and group
      behavior. The institutions were of 4 types: a geriatric hospital, a special
      nursing home for the aged, a home for the elderly and a home with moderate fees.
      The assessment of social life demonstrated significant correlation between the
      revised version of Hasegawa's Dementia Scale, activity of daily living and
      physical conditions. Inter-institution comparisons revealed significant
      differences in terms of economic conditions for the home for the elderly, family
      conditions for the home with moderate fees, and family relationships and group
      behavior for the geriatric hospital. Total grades across the 5 items were
      significantly lower for the geriatric hospital cases. This assessment proved
      useful to illuminate aspects of social life of the elderly in institutions.

PMID- 8295354
TI  - [Clinical evaluation of age-related changes of bone mineral content of cortical
      and trabecular bones by dual energy QCT].
AB  - The potential capability of a new dual energy (DE) quantitative computed
      tomography (QCT) method, 4-equation 4-unknown method (DEQCT4E-4U), was evaluated
      for estimation of bone mineral density (BMD) as well as bone mineral content/cm
      width (BMC) in trabecular bone of lumbar vertebrae. Cortical BMD and BMC were
      also estimated by the single energy QCT method (SEQCT 80 kVp) and the age-related
      change of cortical BMD and the cortical BMC/trabecular BMC ratio was also
      studied. The result indicated that the estimation of the BMD combining analysis
      of BMC in trabecular bone obtained by the present method provides further
      knowledge concerning vertebral trabecular bone mineral status. The profiles of
      the age-related changes of the cortical BMD and cortical BMC/trabecular BMC ratio
      in females were markedly different from those in males. These results indicated
      that our method combining analysis of BMC (BMD) of cortical bone and trabecular
      bone was also found to provide valuable information to evaluate the vertebral
      bone mineral status.

PMID- 8295355
TI  - [Clinical characteristics of impacted bile duct stone in the elderly].
AB  - Acute cholangitis due to impacted bile duct stone is sometimes fatal and require
      prompt bile duct decompression. Particularly, AOSC (acute obstructive suppurative
      cholangitis) is the most serious form of bacterial cholangitis and its prognosis
      is usually very poor when treated conservatively. We have been treated impacted
      bile duct stones by decompressing the duct endoscopically. Here, we report the
      characteristics of our elderly patients with impacted bile duct stones who
      received urgent decompression treatment mainly by endoscopic techniques. In the
      endoscopical treatment group, the number of patients with AOSC was 5 out of 46 AC
      (acute cholangitis) patients (11%) under 69 years old, 14 out of 52 (27%) from 70
      to 79 years old, and 12 out of 28 (43%) over 80 years old. Obviously, the
      severity of acute cholangitis (ratio of AOSC to AC) was higher in the elderly.
      This tendency was similar to the patients who received urgent transhepatic
      decompression treatment, although they were small in number. In all the patients
      treated, 7 were classified into the most serious AOSC category with Reynolds'
      sign, and notably 6 out of 7 were over 70 years old. More strikingly, 5 of 7
      patients were over 80, and their mortality rate was indeed high. Thus, in the
      elderly, bacterial cholangitis by impacted bile stones was a very serious
      condition. Especially, the outcome of AOSC over 80 years old with Reynolds' sign
      was very poor, in spite of emergency endoscopic treatment.

PMID- 8295356
TI  - [Endolotherapy of massive bleeding from the small intestinal angiodysplasia in 80
      year-old patient].
AB  - Angiodysplasia is one cause of chronic gastrointestinal tract bleeding that can
      not be difficult to detect. In particular, angiodysplasia in the small intestine
      is very rare and has seldom been reported. An 80-year-old man complained of
      hematochezia and was admitted to other hospital on October 1991. However, no
      bleeding sites in the gastrointestinal tract could be revealed by radiographic
      and endoscopic examinations. After 8 months, he was admitted to our hospital with
      the same symptom on June 1992. He suffered hemorrhagic shock due to continuous
      bleeding. Hypotension and anemia progressed in spite of immediate blood
      transfusion. Emergency angiography revealed extravasation from a peripheral
      branch of the jejunal artery, in addition tortuous and dilated ileal arteries.
      Embolization was performed with the catheter inserted superselectively into the
      nearest arcade of the segmental branch of the vasa recta. After embolization, no
      complications were occurred. He was discharged and is being followed up as an
      outpatient.

PMID- 8295357
TI  - [A case of diffuse panbronchiolitis associated with tracheomalacia].
AB  - A 71-year-old male had suffered from cough with purulent sputum. He was admitted
      to our hospital because of worsening of his symptoms. The chest X-ray film showed
      diffuse nodular shadows and emphysematous changes in both lung fields.
      Transbronchial lung biopsy demonstrated findings compatible with diffuse
      panbronchiolitis (DPB). Bronchoscopy showed the tracheal lumen was sagittaly
      narrowed and membranous portion was protruded into the lumen. The trachea
      completely collapsed when coughing. His disease was diagnosed as saber-sheath
      type tracheomalacia (Johnson III). Tracheomalacia was reported to be observed in
      0.9% of patients examined by bronchoscopy. The dominant type of tracheomalacia is
      crescent type, and saber-sheath type is rare. Chronic airway inflammation with
      DPB might have exacerbated the tracheomalacia in this case.

PMID- 8295358
TI  - [Two elderly cases with acute exacerbation of interstitial pneumonia].
AB  - We studied two cases of the elderly with acute exacerbation of interstitial
      pneumonia to elucidate a prognostic role of super oxide generation in peripheral
      whole blood. The first case was a 70-year-old man, who presented with acute
      exacerbation of interstitial pneumonia and was hospitalized. Following steroid
      pulse therapy, CRP, ESR, blood-gas and his physical condition improved, resulting
      in successful discharge. In this case, super oxide generation standardized by the
      number of neutrophils (K) decreased to less than 1.0 in association with the
      improvement of physical condition. The second case was a 92-year-old woman in
      whom acute exacerbation of interstitial pneumonia was diagnosed. While the pulse
      therapy, CRP, LDH and blood-gas temporarily improved, K was continuously greater
      than 1.0 and the physical condition worsened, resulting in her death. These cases
      suggest that the measurement of super oxide generation in peripheral whole blood
      may play a useful role in assessing the prognosis of the elderly with acute
      exacerbation of interstitial pneumonia.

PMID- 8295359
TI  - [A case of elderly Hashimoto disease presenting malignant lymphoma, gastric
      cancer and colon cancer].
AB  - An 87-year-old woman, who had been suffering from hypothyroidism and had been
      treated as an outpatient at our department since 1982, noticed left cervical
      swelling toward the end of November 1992. Because ultrasonic examination revealed
      a mass in her thyroid gland, she was admitted for a closer examination and
      additional treatment. Biopsy of thyroid gland revealed non-Hodgkin's lymphoma
      (NHL; the diffuse small cell type, B-cell origin). A part from the swelling of
      thyroid gland and the left cervical lymph node, performance of various
      examinations did not detected any other NHL lesions. Therefore, it was classified
      as stage II NHL according to the Ann Arbor classification. Laboratory data on
      admission were as follows; WBC 4,400/microliters, Hb 13.6 g/dl, platelet count
      10.1 x 10(4)/microliters, GOT 51 IU/l, GPT 31 IU/l, TSH 1.17, free-T4 1.03, free
      T3 2.04, and microsome test 1,600 x. Those data indicated marked hypothyroidism.
      In addition, stage IIa and IIc gastric cancers were detected by the examination
      with gastric endoscopy performed for stage classification. Both were
      adenocarcinomas. Because polyps were found in her sigmoid colon with colonoscopy,
      polypectomy was performed. The polyps were diagnose histologically as moderately
      differentiated adenocarcinoma. On July 20, COP-BLAM therapy was started (CPM 600
      mg div, VCR 1.2 mg iv, ADR 30 mg iv on day 1, PDN 40 mg p.o and PCZ 100 mg p.o.
      on days 1-10, BLM 7.5 mg div on day 14). Subsequently, the left cervical lymph
      node swelling disappeared, and shrinkage of the mass in the thyroid gland was
      observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295360
TI  - [Gadolinium-DTPA magnetic resonance imaging in the diagnosis of left atrial
      myxoma in the elderly].
AB  - A 85-year-old woman consulted our hospital with general fatigue, palpitation and
      chest discomfort changing with different postures. Her electrocardiogram showed
      sinus tachycardia, atrial premature beats and left atrial overload. 53%
      cardiothoracic ratio, slightly protruding third arch of the cardiac silhouette
      and dilated pulmonary artery were seen on the chest X-ray. Two dimensional
      echocardiography revealed a mass in the left atrium although the quality of
      echocardiography was suboptimal due to her thoracic deformity. There was no
      uptake of T1-201 or Ga-67 by the mass. The four-chamber view of Tc-99m ECG-gated
      SPECT radionuclide angiocardiography showed a filling defect in the left atrium.
      The T1 weighted magnetic resonance imaging revealed a left atrial mass with
      relatively low signal intensity. After intravenous injection of Gadolinium-DTPA
      the signal intensity of the mass increased significantly and the contrast of the
      mass was improved. The size of the mass was 4 x 4 x 3 cm with a stalk connecting
      to the interatrial septum. These findings were compatible with left atrial
      myxoma. Gadolinium-DTPA magnetic resonance imaging is useful in diagnosing left
      atrial myxoma because it provides information on the size, anatomical location,
      relationship with other cardiovascular structures and even the characteristics of
      the mass.

PMID- 8295361
TI  - [Statistical analysis of bone density in patients with Parkinson's disease].

PMID- 8295362
TI  - Effects of topical application of UF-021, a novel prostaglandin-related compound,
      on aqueous humor dynamics in rabbit.
AB  - The mechanism underlying the intraocular pressure (IOP) lowering effect of a
      novel prostaglandin-related compound, (+)-isopropyl Z-7-[(1R,2R,3R,5S)-3,5
      dihydroxy-2-(3-oxodecyl)-cyclopentyl]hept-5 -enoate (UF-021), and the influence
      of this new hypotensive agent on the permeability of the blood-aqueous barrier
      (BAB) were studied in albino rabbits. A single instillation of 0.06% UF-021
      significantly lowered the IOP with a peak reduction of 5.2 mmHg without changing
      the aqueous flow rate. Uveoscleral outflow and outflow facility to general blood
      circulation were both increased. The BAB permeability evaluated with fluorescein
      isothiocyanate-labeled rabbit albumin (FITC-RA) showed approximately sixfold
      increase after a single instillation of 0.06% UF-021, which suggested a drug
      induced compromise of the rabbit BAB.

PMID- 8295363
TI  - Clinical efficacy of PhXA34 and PhXA41, two novel prostaglandin F2 alpha
      isopropyl ester analogues for glaucoma treatment.
AB  - Four clinical studies were performed in 54 healthy Japanese volunteers to assess
      the efficacy and the safety of two phenyl-substituted PGF2 alpha-isopropyl ester
      analogues, PhXA34 and PhXA41 after both single and repeated administrations.
      PhXA34 and PhXA41 reduced intraocular pressure (IOP) significantly in a dose
      dependent way. The maximum IOP reductions were 14.5% to 17.5% with baseline
      adjustment at 10 to 12 hours after a single administration. No transient early
      elevation in IOP after treatment was observed. Based on the maximum IOP reducing
      effect of 1 microgram of PhXA34 and PhXA41, PhXA41 appeared to be at least 1.5
      times more active than PhXA34. Tachyphylaxis of the ocular hypotensive effect did
      not develop during repeated administration for 5 days. A mild conjunctival
      hyperemia occurred in some subjects at high doses; it tended to diminish with
      time during the repeated administration of both drugs. Neither PhXA34 nor PhXA41
      caused any change at any time in the aqueous flare intensity measured with a
      laser flare-cell meter. There were no changes in pupillary diameter after
      treatment. Each drug was well tolerated and caused no other ocular or systemic
      side effects.

PMID- 8295364
TI  - Ocular hypotensive effect of PhXA41 in patients with ocular hypertension or
      primary open-angle glaucoma.
AB  - A study was carried out to assess the clinical efficacy of PhXA41, a new phenyl
      substituted prostaglandin F2 alpha-isopropyl ester analogue, using a single
      administration in 35 subjects with ocular hypertension or primary open-angle
      glaucoma. PhXA41 caused a dose-dependent intraocular pressure (IOP) reduction
      which continued 24 hours or more after administration. The mean IOP reduction 8
      hours after treatment compared with the baseline IOP was 3.4, 4.9 and 5.9 mmHg
      for the doses of 25, 50 and 100 micrograms/ml, respectively. Although slight
      conjunctival hyperemia occurred in some patients, it disappeared by the next day
      with no treatment. No aqueous flare or cells were detected, no significant change
      in pupillary diameter was found, and no systemic symptom was reported. Thus,
      PhXA41 was well tolerated in subjects with ocular hypertension or primary open
      angle glaucoma. Furthermore, its IOP-reducing effect was so long-lasting that a
      once daily application may suffice for clinical use.

PMID- 8295365
TI  - Ocular manifestations in Japanese patients with human immunodeficiency virus
      infection.
AB  - The ocular manifestations in 65 Japanese human immunodeficiency virus (HIV)
      seropositive patients were examined. Based on the cumulative totals, 22 of the
      cases had acquired immunodeficiency syndrome (AIDS), 17 had AIDS-related complex
      (ARC), and 35 were asymptomatic carriers (AC), including 4 AIDS cases who had
      progressed from ARC and 5 ARC cases from AC. Seventy-seven percent of the AIDS
      cases had ocular manifestations, including cotton-wool spots (50%), retinal
      hemorrhages (59%), cytomegalovirus retinitis (46%) and pupil abnormalities (14%).
      The ocular signs were also seen in 71% of the ARC cases and 37% of the AC cases.
      In Japanese HIV-seropositive patients, ocular manifestations are also as common
      as in Western HIV-seropositive patients.

PMID- 8295366
TI  - Preoperative evaluation by laser interferometry in cataractous eyes with
      retinitis pigmentosa.
AB  - Measurements of visual acuity were carried out preoperatively by laser
      interoferometry in 16 cataractous eyes of 13 patients with retinitis pigmentosa
      who were older than 60 years of age. Subsequently, all patients underwent
      uneventful extracapsular cataract extraction and posterior chamber intraocular
      lens implantation. Postoperative visual acuity, which was evaluated as the best
      acuity during the first postoperative year, was improved in all eyes and it
      correlated well with the preoperative acuity determined by laser interferometry.
      Laser interferometry can be useful in predicting postoperative acuity and
      deciding on cataract surgery for elderly cataractous patients with retinitis
      pigmentosa.

PMID- 8295367
TI  - Internal eye wall resection for posterior uveal melanoma.
AB  - The long-term follow-up results were reported on 23 patients who underwent
      internal surgical resection between 1984 and 1991 for presumed posterior
      choroidal melanoma. The melanomas were located within 1- to 2-disc diameters of
      the disc or the fovea. Follow-up ranged from 7 to 84 months with 57% of the
      patients followed for more than 4 years. Final Snellen visual acuities varied
      from 20/40 to no light perception; 43% of the patients attained 20/400 or better.
      Two patients required enucleation; one had intraocular tumor recurrence and
      subsequently died of liver metastasis, and the other patient developed a blind,
      painful eye secondary to retinal detachment with proliferative vitreoretinopathy.
      Three of the 23 patients have died of choroidal melanoma metastatic to the liver
      at 15 months, 57 months, and 84 months following internal resection,
      respectively. Two of the 3 patients had spindle B-cell tumors and one had a mixed
      cell tumor.

PMID- 8295368
TI  - Occurrence of sequential intraocular tumors: malignant medulloepithelioma
      subsequent to retinoblastoma.
AB  - A 13-year-old boy, whose bilateral retinoblastoma had been treated by enucleation
      (OD) and irradiation (OS), developed anterior staphyloma (OS) necessitating the
      second enucleation. Histopathological, immunohistochemical and electron
      microscopic studies revealed malignant teratoid medulloepithelioma of the ciliary
      body, with demonstrated multipotential histogenesis. This is the first report
      which demonstrates the development of a second malignant intraocular tumor in an
      eye previously affected by hereditary retinoblastoma. Careful monitoring of
      patients who have had hereditary retinoblastoma is necessary because of the
      potential for a second malignancy.

PMID- 8295369
TI  - Severe destruction of the neural integration mechanism for upward eye movements
      in bilateral internuclear ophthalmoplegia.
AB  - The visually elicited saccades and smooth pursuits of a 24-year-old man with
      bilateral internuclear ophthalmoplegia were recorded with an infrared limbus
      reflection technique. Although the amplitude-peak velocity relationship of
      saccades appeared to be normal, all the upward saccades were hypermetric and were
      followed by postsaccadic exponential drifts. The time constant of the
      postsaccadic exponential drifts was 248 +/- 19.5 ms (mean +/- SD). Upward pursuit
      eye movements were also severely disturbed, and only movements with a short
      duration (mean 113.8 ms) and low gain (mean 0.51) were frequently observed. Thus,
      the transformation of a pulse velocity signal for saccades and of a step velocity
      signal for smooth pursuits into step and ramp position commands, respectively,
      was almost completely lost for upward eye movements in this patient because of
      bilateral lesions of the medial longitudinal fasciculus.

PMID- 8295370
TI  - Explant culture of human lens epithelial cells from senile cataract patients.
AB  - Human lens epithelial cells (HLECs) with lens capsules were cultured to
      investigate the morphology and outgrowth potential of the cultured cells.
      Anterior lens capsules obtained during cataract surgery were placed cell side
      down in a medium in culture wells. Cultivation was successful with 24 of 36
      specimens from senile cataract patients. The HLECs grew beyond the capsular edge
      from the third to fifth day after the beginning of cultivation, and extended
      actively to the periphery of the culture well. The cells had extended 2.5 mm
      beyond the capsular edge by the second week and 3.8 mm by the fourth week, but
      outgrowth then stopped. The cells near the capsular edge displayed elongated
      shapes during the earlier period of cultivation, but subsequently formed small
      polygons. The cells in the middle of the zone of outgrowth appeared as polygons,
      and were surrounded by large, irregularly-shaped cells. This study showed that
      HLECs from senile cataract patients have a limited but definitive outgrowth
      potential under explant culture conditions.

PMID- 8295371
TI  - Herpes simplex virus latency in human cornea.
AB  - The authors attempted to demonstrate the latency of herpes simplex virus type 1
      (HSV-1) in corneas obtained during penetrating keratoplasty from patients with
      herpetic stromal keratitis in the nonactive (subsided) stage. The subjects
      comprised 20 patients (9 men, 11 women; average age 43.5 years). Infectious virus
      was not detected in the supernatants following corneal homogenization and
      centrifugation. Latent virus was detected in the cultured supernatants of the
      corneal sections from 8 patients. Although the ganglion trigger theory by Hill et
      al is conventionally supported as the mechanism of recurrence of herpetic
      keratitis, the present results suggest a ganglion and skin trigger theory, in
      which proliferation from latent HSV-1 in the cornea (peripheral tissue) might
      stimulate the ganglion.

PMID- 8295372
TI  - Membranous cataract in association with aniridia.
AB  - A case of aniridia associated with a membranous cataract and glaucoma in a 52
      year-old woman was reported. Bilateral ocular findings included marked hypoplasia
      of the iris, goniodysgenesis, corneal opacification with superficial
      vascularization, macular hypoplasia and glaucoma. A membranous cataract was found
      in the right eye. The intraocular pressure was abnormally high. Since
      trabeculectomy on the right eye was ineffective, a seton procedure was carried
      out. During the follow-up period, the membranous cataract in the right eye
      spontaneously moved from its original position and floated in the vitreous,
      maintaining its shape.

PMID- 8295373
TI  - Changes in nystagmus after simultaneous surgery for bilateral congenital
      cataracts.
AB  - The presence of nystagmus has been considered as an indicator of poor prognosis
      in infants with bilateral congenital cataracts. However, of the 10 infants with
      preoperative nystagmus reported in this study, after simultaneous surgery for
      bilateral congenital cataracts, 5 cases showed a resolution of nystagmus or
      reduction to latent nystagmus postoperatively. This study was carried out to
      clarify what factors resolved or reduced the preoperative nystagmus. Those 5
      cases in whom nystagmus was ameliorated postoperatively were operated on within
      one month after the onset. Age of nystagmus onset, age at surgery or type of
      cataract did not affect this amelioration of nystagmus. In contrast, the 5 cases
      who had no postoperative change in nystagmus were operated on later than this
      period. Our results demonstrate that it is possible to resolve or reduce
      preoperative nystagmus in bilateral congenital cataracts by a simultaneous
      bilateral lens removal within one month after the onset of nystagmus.

PMID- 8295374
TI  - Inositol phosphate-diacylglycerol signaling pathway in regulation of intraocular
      pressure.
AB  - To clarify the role of the inositol phosphate diacylglycerol (PI) signaling
      pathway in the regulation of intraocular pressure (IOP), we examined the effects
      of the tumor promoter phorbol ester (PMA) and Ca ionophore A23187 on IOP
      responses in albino rabbits. It was known that PMA stimulates protein kinase C
      (PKC) directly and that A23187 elevates intracellular Ca2+ concentration. In this
      study, the topical application of 10 microM PMA or 15 microM A23187 slightly
      reduced IOP. However, when both 10 microM PMA and 15 microM A23187 were topically
      applied the IOP was significantly reduced between 2 and 10 hours after A23187
      application. The maximum IOP decrease was 5.0 mmHg at 3 hours. This decrease was
      inhibited by pretreatment with 0.5 microM staurosporin, a PKC inhibitor. These
      findings suggest that the PI signaling pathway somehow mediates aqueous dynamic
      changes in the eye.

PMID- 8295375
TI  - Clinical application of new membrane filter for cytopathological diagnosis in
      ophthalmology.
AB  - In order to evaluate the clinical usefulness of a new membrane filter method,
      PORETEC, for cytopathological diagnosis in ophthalmology, we performed a
      comparative study on conjunctival cell specimens using this method and a
      previously developed cytocentrifugation method. The subjects were 5 normal male
      volunteers (6 eyes) with an average age of 33 years. The conjunctival cells were
      obtained by brush cytology, and processed for both the new membrane filter and
      the cytocentrifugation methods. The total numbers of epithelial cells obtained by
      both methods were counted under a light microscope. The number of cells obtained
      by the cytocentrifugation method was 4933 +/- 2338 for each specimen, whereas
      that by the new membrane filter method was 12436 +/- 5281 (mean +/- SD). The
      difference was statistically significant (Wilcoxon signed-rank test, P < 0.05).
      The new membrane filter diagnostic method was also applied to specimens of
      aqueous humor from patients with uveitis or vitreous body from patients with
      proliferative diabetic retinopathy or endophthalmitis. The new method provided
      excellent cytopathological specimens which were also applicable for special
      staining and immunocytochemical study. We concluded that the new membrane filter
      is quite useful for cytopathological diagnosis of ocular fluid specimens.

PMID- 8295377
TI  - [Morphofunctional aspects in surgery of chronic pancreatitis].
AB  - On the basis of 15-year experience in the treatment of patients with chronic
      pancreatitis, among which 236 patients underwent operation, the authors describe
      the examination scheme and discuss the indications and various methods for
      treatment of the disease. Particular attention is bestowed upon morphological
      changes of the pancreas, including ultrastructural analysis, as well as on the
      study of the functional condition by evaluation of the pure pancreatic
      secretions. The importance of the extrasecretory function of the pancreas in
      choosing the method of direct intervention on the organ is shown. The indications
      for nonoperative, endoscopic, and surgical treatment of chronic pancreatitis are
      determined according to the morphofunctional changes.

PMID- 8295376
TI  - [Prognosis and daily evaluation of changes in the condition of patients with
      peritonitis].
AB  - The authors examined 159 patients with peritonitis (87 with the generalized form
      and 72 patients with the diffuse form) and conducted a statistical analysis of
      the findings. Quantitative and some qualitative parameters of the patients were
      studied. The Student and Wilcoxon criteria and the correlation and discriminant
      analysis were used in construction of the determinative rules. Two groups of
      discriminant functions were constructed to obtain the prognosis of the outcome of
      peritonitis in a patient with daily appraisal of the dynamics of changes in his
      condition. The first group of prognostic indices was obtained only from the
      qualitative data. The second group of "simplified" prognostic indices was
      constructed with the use of parameters which are used most frequently in the wide
      clinical practice. The quality of both groups of discriminant functions proved to
      be comparable, i. e. both sets of determinative rules may be used in medical
      practice to evaluate the condition of a patient with peritonitis and construct
      the prognosis of the outcome of the disease.

PMID- 8295378
TI  - [Effect of intestinal decompression with intubation on portal and systemic
      bacteremia in patients with peritonitis].
AB  - Examination of 55 patients, who underwent operation for generalized peritonitis
      of various etiology, included comparative appraisal of the degree of portal and
      systemic bacteremia and the leukocytic index of intoxication in patients with and
      those without nasointestinal intubation. It was found that the microflora of a
      paretic intestine was one of the most important factors of intoxication in
      patients with peritonitis in the postoperative period. Nasointestinal intubation
      in this case proved to be an effective method for reducing the degree of portal
      and systemic bacteremia and ensured a significant decrease of the degree of
      intoxication as compared to that in the control group.

PMID- 8295379
TI  - [Effect of fragmin, a low-molecular heparin, on hemostasis in patients with
      alimentary-constitutional obesity].
AB  - The authors conducted comparative study of the hemostasis indices before and in
      the immediate period after operation for formation of a small stomach in 31
      patients with stage III-IV alimentary-constitutional obesity, in 50 patients
      without obesity who underwent operation on the stomach, and in 15 volunteers.
      Nonspecific prevention of thrombogenesis was performed in all patients with
      normal weight and those with obesity. Patients with obesity were given in
      addition specific thrombogenesis prevention with nonfractionated heparin (group
      I) and fractionated low-molecular heparin-fragmin produced by KABI (groups II and
      III). Study of the parameters of the hemostasis system in the postoperative
      period showed nonspecific prevention of thrombogenesis to be sufficient to reduce
      the risk of pulmonary artery phlebothrombosis and embolism in most patients
      without obesity. In patients with obesity the probability of phlebothrombosis and
      thromboembolism is much higher, in view of which they must be given heparin in
      addition to nonspecific prevention. Fragmin, as an agent for thrombosis
      prevention, has certain advantages over nonfractionated heparin and should be
      used more frequently in clinical practice in patients of the risk group, e. g.
      with pathological obesity, in a dose no less than 100 U/kg. With the use of
      fragmin laboratory control before each injection is not needed. Administration of
      nonfractionated and fractionated heparins must be combined with bandaging of the
      lower limbs and other measures of nonspecific prevention of thrombogenesis.

PMID- 8295380
TI  - [Radiographic endovascular correction of hyperaldosteronism in patients with
      arterial hypertension].
AB  - The authors describe a new method of X-ray endovascular destruction of the
      adrenal in patients with arterial hypertension and hyperaldosteronism.
      Destruction of the adrenal is accomplished by acute occlusion of its venous
      channel by introduction of a 3% thrombovar solution through a catheter installed
      in the central vein of the suprarenal gland. This method was applied in 22
      patients with arterial hypertension; essential hypertension with secondary
      hyperaldosteronism was found in 18 of them, renoparenchymatous hypertension in 2,
      aldosteroma of the left adrenal in one, and Itsenko-Cushing's disease in one
      patient. Acute occlusion of the adrenal venous channel was achieved in 20
      patients. The intervention normalized blood pressure in 16 and reduced it
      significantly in 4 patients.

PMID- 8295381
TI  - [Reconstructive-plastic operations using microsurgical techniques in oncology].
AB  - With the successful development of combined treatment of malignant tumors, the
      performance of organ-preserving operations, those with microsurgical techniques
      among others, is now possible. Ninety-five patients with various localization of
      the tumors were operated on. Esophagoplasty using a graft from the greater
      curvature of the stomach with venous shunting, and segmental esophagoplasty with
      the small intestine were conducted in 63 patients, plastics of the lower limb in
      25 patients, and plastics of the organs of the head and neck in 7 patients.
      Vascular complications were encountered in 11.5%. The grafts healed completely in
      93.7%. Preoperative radiotherapy and chemotherapy were the main complicating
      factors. Microsurgical techniques make it possible to expand the radicalism of
      the operations and improve the rehabilitation of oncological patients. Clear-cut
      indications for such operations must be taken properly into account.

PMID- 8295382
TI  - [Treatment methods in colonic diverticulosis].
AB  - The authors had 662 patients with diverticulosis of the colon under observation.
      Nonoperative treatment for clinically manifested diverticulosis was undertaken in
      226 patients. A good effect was produced in 82.2% of them. An operative
      intervention was conducted on 146 patients. The indication for operation was
      clinically manifested diverticulosis in the absence of an effect of nonoperative
      management in 19 (13%) patients and complicated diverticulosis in 62 (41.3%)
      patients. Various types of reconstructive-restorative operations in many-stage
      treatment of diverticulosis of the colon were conducted in 64 (43.8%) patients.
      Postoperative complications were encountered in 29 (19.7%) patients. Ten (6.8%)
      patients died. The authors conclude that the choice of the volume and method of
      operation should be guided by the patient's general condition, the character of
      the developing complications, the spread of the diverticuli along the colon, and
      the existence or absence of signs of an inflammatory process in the diverticuli.

PMID- 8295383
TI  - [Comparative characteristics of various types of operations performed in
      treatment of diffuse colonic polyposis].
AB  - Diffuse polyposis of the large intestine characterized by the development of
      multiple polyps in it and their subsequent malignant degeneration is one of the
      most severe disease of the gastrointestinal tract. That it must be treated by
      surgery needs no proof. However, the volume and the character of the surgical
      intervention on the large intestine is still a debatable problem. The article
      discusses the experience in the follow-up of 445 patients for periods of 12
      months to 30 years after operation for diffuse polyposis. In 228 patients various
      segments of the large intestine which were free from polyps were not resected.
      During these follow-up periods malignant tumors developed in the preserved parts
      of the large intestine in 10.1% patients and intensive growth of polyps was
      encountered in 3.5% of patients. The frequency of carcinoma development depended
      significantly less on the length of the follow-up period and much more on the
      character of affection of the preserved parts of the large intestine with the
      polyps.

PMID- 8295385
TI  - [N. I. Pirogov--"marvelous doctor"].

PMID- 8295384
TI  - [Late results of surgical treatment of differentiated thyroid cancer].
AB  - Retrospective analysis of 94 patients who were operated on in the clinic in 1981
      1987 for differentiated carcinoma of the thyroid was conducted with the use of
      the classification of the disease formulated by the American United Cancer
      Committee and the Committee TNM of the International Anticancer Union which takes
      into account the patients's age. According to the new system of stages, 34
      patients under 45 years of age with any indices of T, N, and MO, and 14 patients
      over 45 years of age with indices Tl, NO, and MO were related to stage I. The
      postoperative follow-up period ranges from 4 to 9.5 years. During that time,
      metastases to the regional lymph nodes developed in 9 (9.5%) patients, remote
      metastases in one (1.1%) patient, and local recurrence of the tumor was diagnosed
      in 14 (14.5%) patients, with the tumor recurring in most or them 5 years after
      the operation. Six (6.4%) patients died from carcinoma. The work appraises the
      prognostic significance of dividing the patients according to stages from the
      standpoint of the tendency to recur and metastasize, and the carcinoma mortality
      rate. It is shown that patients who underwent operation for thyroid carcinoma
      must be kept under observation for a long time.

PMID- 8295386
TI  - [Surgical approach in ruptured aneurysm of the abdominal aorta].

PMID- 8295387
TI  - [Clinical evaluation of some pancreonecrotic syndromes].
AB  - The author analysed 384 cases of pancreonecrosis with clinico-morphological
      verification of the diagnosis in the first 3-4 days of the disease. The clinical
      manifestations of four most demonstrative syndromes were compared with the
      peculiarities of the morphological components of pancreonecrosis. Arguments are
      presented in favor of the assumption that analysis of the clinical pictures
      allows not only the presumptive diagnosis of destructive pancreatitis to be made
      in the first days of the disease, but also to prognosticate the clinical course
      of the disease.

PMID- 8295388
TI  - [Choice of bile-diverting operations in neoplastic obstruction of the distal
      common bile duct].
AB  - Analysis of clinical material of 206 patients with tumor obstruction of the
      distal part of the common bile duct allowed the conclusion to be made on the
      expediency of applying endoscopic methods for jaundice correction as the first
      stage in preparation for the operation (122 patients) and also as the only and
      final operation (70 patients). Study of the immediate and late-term results of
      different variants of operations for bile diversion in obstruction of the distal
      choledochus (203 operations) showed the superiority of the Roux
      hepaticoejunoanastomosis in which recurrent jaundice due to obstruction of the
      cystic duct does not occur, as is encountered in creation of a
      cholecystoejunoanastomosis, and there are no conditions for the development of
      ascending cholangitis.

PMID- 8295389
TI  - [The causes of the so-called post-cholecystectomy syndrome and the possibilities
      of its timely recognition].
AB  - A simple scheme for the examination of patients for identifying the causes of the
      so-called postcholecystectomy syndrome (PCES) is suggested from experience in the
      examination of 1,712 patients with this syndrome. Three groups of patients are
      distinguished. First group--individuals with an external biliary fistula. Second
      group--patients with jaundice or with signs of jaundice suffered in the past
      after an operation. Third group--patients with abdominal pain and dyspeptic
      disorders after removal of the gallbladder but without an external biliary
      fistula and jaundice. The author gives a clinical evaluation and recommendations
      for using in establishing the diagnosis ultrasonic examination,
      cholefistulography, intravenous cholegraphy, percutaneous transhepatic
      cholangiography, retrograde cholangiopancreaticography, and computerized
      tomography conformably to the distinguished groups. After the examination was
      completed, the need for a repeated operation or active treatment (endoscopic
      papillotomy, removal of stones through the fistula) occurred in 98.7% of patients
      of the first group, in 73.8% of those in the second group, and in 15.7% of
      patients of the third group.

PMID- 8295391
TI  - [Casuistic cases teach (lecture)].

PMID- 8295390
TI  - [Internal biliodigestive fistulas].
AB  - Experience in surgical treatment of 53 patients with internal biliodigestive
      fistulas is analysed. The formation of the fistula in all cases was caused by
      cholelithiasis with obstruction of the bile ducts, purulent cholangitis,
      angiocholitis, cholangiolytic abscesses of the liver, pancreatitis, hepatitis, as
      well as cholelithic ileus. Cholecystectomy, removal of the stones from the bile
      ducts, restoration of the main route of bile drainage, elimination of the
      pathological communication, and closure of the defect in a hollow organ should be
      considered the operation of choice. In cholelithic ileus operation for correction
      of the intestinal obstruction is also expedient. Postoperative complications were
      encountered in 35.8% of cases. Hepatorenal insufficiency developed in 8,
      incompetence of the choledochus sutures in 3, an external biliary fistula in 2,
      hepatic abscess in 1, pancreatitis in 2, and suppuration of the postoperative
      wound in 3 patients. Among the 53 patients treated by operation, 49 (92.5%)
      recovered and 4 (7.5%) died from various postoperative complications.

PMID- 8295392
TI  - [Difficulties and errors in diagnosis of intrathoracic adipose tumors].
AB  - The authors treated 9 patients with intrathoracic adipose tumors of rare
      localization. In 4 cases the lipoma arose from the thoracic wall, in 2 directly
      from the mediastinum, and in another 2 from the pericardium. Lipoma of the lung
      and, 6 years later, liposarcoma of the diaphragm were removed in one patient.
      Tomography (3), bronchoscopy (2), diagnostic pneumothorax (5), thoracoscopy (3),
      and scanning of the thyroid gland (1) were performed to make a precise diagnosis.
      The nosological diagnosis was established in none of the patients, the topic
      diagnosis was most difficult in lipomas of organs. The diagnostic errors are
      analysed and the clinical pictures are described.

PMID- 8295393
TI  - [Method for draining purulent parts of the liver].
AB  - Percutaneous draining of purulent cavities in the liver is an effective method
      for the treatment of pyogenic diseases of the organ. The traditional method,
      however, has some shortcomings which often lead to serious complications
      (intraperitoneal hemorrhage, escape of bile, breaking away of the catheter,
      hypostatic pneumonia, etc). The work deals with the results of treatment of 32
      patients with purulent diseases of the liver. Abscess of the liver was found in 8
      patients, subdiaphragmatic abscess in 6, suppurating hydatid cyst in 8,
      nonparasitic cyst in 5 patients. In 18 patients the traditional method of
      draining was applied, in 14 patients draining was conducted by a method suggested
      by the authors. Complications occurred in 11 patients treated by the traditional
      method, whereas in patients treated by the improved method the postoperative
      course was uneventful, no complications were encountered. Thus, the improved
      method for draining purulent cavities in the liver reduces significantly the
      incidence of postoperative complications and improves the results of treatment.

PMID- 8295394
TI  - [Boris Fedorovich Divnogorskii (birth centenary)].

PMID- 8295395
TI  - The carbohydrate-deficient glycoprotein syndromes: an overview.
AB  - The carbohydrate-deficient glycoprotein (CDG) syndromes are a newly recognized
      family of diseases with autosomal recessive inheritance. The basic defects are
      probably in the glycosylation pathway (endoplasmic reticulum, Golgi apparatus or
      post-Golgi). In the present state of our knowledge the central nervous system is
      always severely affected but nearly all other organs are involved to a variable
      degree. Like the peroxisomal disorders they also comprise dysmorphic features,
      the most typical being an abnormal distribution of subcutaneous adipose tissue. A
      reliable diagnostic test is isoelectric focusing of serum transferrin showing a
      cathodal shift as a consequence of the partial sialic acid deficiency. Prenatal
      diagnosis and heterozygote detection are not yet available. These diseases should
      be differentiated from secondary CDG syndromes such as classical galactosaemia.

PMID- 8295396
TI  - 2-Ketoglutarate dehydrogenase deficiency, a rare cause of primary
      hyperlactataemia: report of a new case.
AB  - Two new familial cases of 2-ketoglutarate dehydrogenase (2-KGD) deficiency are
      reported: a girl who died at 10 years and a boy, still alive at 4 years, born to
      consanguineous parents. The cases developed progressively severe encephalopathy
      with axial hypotonia, psychotic behaviour, pyramidal symptoms and failure to
      thrive. Both children exhibited permanent lactic acidosis with acute episodes
      during emotional stress and various infections, associated with elevated
      lactate/pyruvate (L/P) ratio and slightly decreased ketone body ratio in plasma.
      In fibroblasts, the L/P ratio was greatly increased in the boy. No respiratory
      chain complex deficiency could be demonstrated in cultured fibroblasts or in
      mitochondria isolated from a muscle biopsy performed on the boy. In muscle
      isolated mitochondria, a progressive decrease of the rate of glutamate oxidation
      was observed after ADP addition; the rate of 2-ketoglutarate oxidation was low in
      the absence of ADP and did not increase after ADP addition. 2-KGD deficiency was
      demonstrated in fibroblasts from both children and in the boy's muscle and
      myoblasts. The 2-KGD complex is composed of three separate enzymes: E1, E2 and
      E3. We could demonstrate in our patient that the E1 and E3 subunits were normal,
      suggesting that the E2 component could be responsible for the defect.

PMID- 8295397
TI  - Reliable prenatal diagnosis of Canavan disease (aspartoacylase deficiency):
      comparison of enzymatic and metabolite analysis.
AB  - Prenatal diagnosis has been undertaken in 17 pregnancies in 15 families at risk
      for aspartoacylase deficiency. Amniocentesis was at 14-18 weeks gestation
      followed by measurement of amniotic fluid N-acetyl-L-aspartate (NAA) levels in
      all pregnancies and amniocyte aspartoacylase activity in most pregnancies. In one
      case amniocentesis was performed at 11 weeks gestation in conjunction with
      chorionic villus sampling. At 14-18 weeks of gestation, control levels of NAA
      were 0.30-2.55 mumol/L. The fetus was predicted to be affected in 8 of the
      pregnancies, 4 of which were confirmed by enzyme analysis on fetal tissue and 2
      by the clinical and metabolic expression of Canavan disease in a newborn. In two
      cases there was no fetal tissue available for enzyme confirmation. One of these
      had the highest amniotic fluid NAA level (8.68 mumol/L) and in the other
      pregnancy there were two amniocenteses, both with markedly elevated levels. Of 9
      fetuses predicted to be normal, 8 newborns were clinically and biochemically
      normal. A single case with amniotic fluid NAA in the normal range (1.56 mumol/L,
      measured in one laboratory only) resulted in an aborted fetus in whom
      aspartoacylase was deficient in cultured skin fibroblasts. We propose that
      amniotic fluid NAA levels remain the best predictor of an affected fetus and
      recommend that the assay be performed in multiple laboratories.

PMID- 8295398
TI  - Prenatal analysis in two suspected cases of glutathione synthetase deficiency.
AB  - Prenatal diagnosis was performed in a family affected by generalized glutathione
      synthetase deficiency. The disorder is transmitted by autosomal recessive
      inheritance. The first child born in this family died of the disorder at 6 weeks
      of age. Prenatal diagnosis was performed in two subsequent pregnancies. Amniotic
      fluid samples were collected by amniocentesis in the 16th and 17th weeks of
      pregnancy, respectively. In the case of the second pregnancy the concentration of
      5-oxoproline in the amniotic fluid was measured by stable isotope dilution, while
      both stable isotope dilution and glutathione synthetase activity measurements
      were employed in the prenatal analysis of the third pregnancy. The 5-oxoproline
      concentration in the second pregnancy was even lower than that of the controls
      and in the case of the third pregnancy the results fell within the control range.
      The second pregnancy resulted in the birth of a clinically healthy girl, and the
      outcome of 5-oxoproline concentration in a urine sample taken just after birth
      confirmed the unaffected state. The third pregnancy resulted in the birth of a
      healthy boy at term, and the 5-oxoproline concentration in his urine and the
      glutathione synthetase activity in haemolysates were determined. The results
      confirmed that this infant was also unaffected and he apparently had two normal
      alleles for the enzyme.

PMID- 8295399
TI  - Unreliability of platelet glucose-6-phosphatase for the diagnosis of glycogen
      storage disease type Ia.
AB  - The diagnosis of glycogen storage disease type Ia currently uses enzyme analysis
      of liver tissue. This requires liver biopsy in the at-risk neonate or fetus.
      Conflicting reports have appeared in the literature on the use of peripheral
      platelet glucose-6-phosphatase activity for the diagnosis of this disorder. We
      have applied a sensitive radiometric assay system to the measurement of glucose-6
      phosphatase activity in peripheral platelets. Two families with affected members
      were analysed, revealing no differences in glucose-6-phosphatase activity as
      compared with control values. Platelet measurement of glucose-6-phosphatase does
      not appear to be useful for the diagnosis of glycogen storage disease type Ia.

PMID- 8295400
TI  - Marked elevation of urinary 3-hydroxydecanedioic acid in a malnourished infant
      with glycogen storage disease, mimicking long-chain L-3-hydroxyacyl-CoA
      dehydrogenase deficiency.
AB  - An infant with glycogen storage disease and prolonged malnourishment showed a
      urinary organic acid profile during an episode of fasting hypoglycaemia with
      inappropriate hypoketotic dicarboxylic aciduria that was indistinguishable from
      that reported in long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency.
      Although there was a striking elevation of urinary 3-hydroxydecanedioic acid, the
      ratios between hydroxydicarboxylic acids were consistent with values reported to
      be indicate of medium-chain acyl-CoA dehydrogenase deficiency. We suspect that
      the fasting 3-hydroxydicarboxylic aciduria was attributable to secondarily
      impaired enzyme activities, the consequence of malnutrition, early infancy,
      and/or glycogen storage disease. Caution is advised in the interpretation of
      urinary organic acid patterns that indicate a 3-hydroxydicarboxylic aciduria, as
      well as an inappropriate hypoketotic dicarboxylic aciduria, as they may represent
      non-specific findings.

PMID- 8295401
TI  - Specificity of PCR-SSCP for detection of the mutant ornithine transcarbamylase
      (OTC) gene in patients with OTC deficiency.

PMID- 8295402
TI  - Propionic acidaemia: sequence analysis of mutant mRNAs from Japanese beta subunit
      deficient patients.

PMID- 8295403
TI  - Peroxisomal 3-ketoacyl-CoA thiolase is partially processed in fibroblasts from
      patients with rhizomelic chondrodysplasia punctata.

PMID- 8295404
TI  - Quantitative analysis of amniotic fluid pyrimidines for the prenatal diagnosis of
      hereditary orotic aciduria.

PMID- 8295405
TI  - Molecular analysis of two Japanese cases of Denys-Drash syndrome.

PMID- 8295407
TI  - Familial encephalopathy and L-2-hydroxyglutaric aciduria.

PMID- 8295406
TI  - Clinical and biochemical phenotype of the MELAS mutation.

PMID- 8295408
TI  - Transient neonatal galactosaemia identified by newborn screening.

PMID- 8295409
TI  - A new case of hyperoxaluria type II.

PMID- 8295410
TI  - Unusual biochemical presentation of GM1 gangliosidosis: markedly elevated levels
      of multiple plasma lysosomal enzyme activities.

PMID- 8295411
TI  - A Chinese case of hereditary xanthinuria.

PMID- 8295412
TI  - Molybdenum cofactor deficiency can mimic postanoxic encephalopathy.

PMID- 8295413
TI  - UDP galactose-4-epimerase deficiency in a 5.5-year-old girl with unilateral
      cataract.

PMID- 8295414
TI  - Late onset of cystinuria in a case of gyrate atrophy.

PMID- 8295415
TI  - Predictive value of plasma catecholamine levels in neonatal detection of Menkes
      disease.

PMID- 8295416
TI  - Haemodialysis and continuous veno-venous haemofiltration in a patient with
      hyperargininaemia and acute renal failure.

PMID- 8295417
TI  - Caprine beta-mannosidosis: aberrant phenotype in a 5-month-old euthyroid animal.

PMID- 8295418
TI  - Postoperative metabolic decompensation in maple syrup urine disease is completely
      prevented by insulin.

PMID- 8295419
TI  - Monocytes, not lymphocytes, show increased fructose-1,6-diphosphatase activity
      during culture.

PMID- 8295420
TI  - Farber disease with prolonged survival.

PMID- 8295421
TI  - Sudden onset of ornithine carbamoyltransferase deficiency after aspirin
      ingestion.

PMID- 8295422
TI  - Prenatal detection of Canavan disease by measurement of N-acetyl-L-aspartate in
      amniotic fluid.

PMID- 8295423
TI  - Endocarditis after ciprofloxacin therapy for enterococcal pyelonephritis with
      bacteremia.

PMID- 8295424
TI  - A New World order: is big brother watching your medical practice?

PMID- 8295425
TI  - Go directly to jail, do not pass go, do not collect $200!--TennCare strategies
      and antitrust hazards.

PMID- 8295426
TI  - Warning! health care plan hazardous to patient care!

PMID- 8295428
TI  - Growth factors accelerate epithelial repair in sheep trachea.
AB  - Toxic gases and fumes have been shown to be injurious to the upper airways.
      Repair of this injury involves proliferation and migration of surviving
      nonciliated cells, followed by differentiation to a normal phenotype. Because
      recent results suggested that growth factors could improve the outcome of an
      airway injury, we undertook this study to determine the efficacy of these
      materials as an initial treatment to accelerate the healing process. In 24
      anesthetized sheep, a portion of the trachea was exposed to smoke from
      smouldering cotton cooled to 37 degrees C. Twelve received aerosolized epidermal
      growth factor plus platelet derived growth factor, while twelve received placebo.
      At 10 days after injury, nonciliated and ciliated cells were totally absent in
      the injured trachea receiving the placebo. In animals receiving growth factors,
      nonciliated and ciliated cells, however, were present (56% and 31% of uninjured
      trachea, respectively). At 13 days after injury, nonciliated and ciliated cell
      counts in those receiving placebo were 67% and 33% of uninjured, respectively. In
      sheep receiving growth factors, tracheal nonciliated and ciliated cell counts had
      increased to 105% and 64% of uninjured trachea, respectively. We conclude that
      growth factors therapy after airway injury stimulates cell proliferation and
      differentiation, and this therapeutic intervention to accelerate the repair
      process in acute airway injury is an approach applicable to humans.

PMID- 8295427
TI  - Flow-regulatory function of upper airway in health and disease: a unified
      pathogenetic view of sleep-disordered breathing.
AB  - Although the Starling resistor behavior of the upper airway during sleep has been
      well established in health and disease, its physiological implications have not
      been fully appreciated. The purposes of the present communication are to reassess
      the current state of knowledge within the framework of the Starling resistor
      concept and to examine the implications of the concept on homeostatic feedback
      respiratory control and the pathogenesis of the sleep apnea syndrome. The main
      inferences drawn from the assessment include: (1) Owing to the Starling resistor
      properties of the upper airway and the well-organized neurochemical control
      mechanism, the upper airway performs important homeostatic flow regulatory
      function; it appropriately dampens the potentially unstable breathing during
      sleep and prevents the PaCO2 from falling below the apneic threshold; (2) Under
      certain conditions, the upper airway flow regulatory function fails to achieve
      appropriate dampening, leading to development of a variety of sleep-related
      breathing disorders that include underdamping due to overly sensitive central
      chemoresponsiveness and/or excessive lung to chemoreceptor transport lag--central
      sleep apnea; overdamping due to upper airway obstructive dysfunction--obstructive
      sleep apnea and/or hypopnea; and, finally, conditions with mixed features of
      central underdamping with coexisting collapsible upper airway; and (3) Successful
      treatment of these conditions requires restoration of appropriate damping. The
      overdamping imposed by the faulty upper airway is effectively reduced by surgical
      and medical approaches, and by application of nasal continuous positive airway
      pressure (CPAP). Reduction of PaCO2 by use of acetalzolamide and/or aminophylline
      reduces the plant gain, thus effectively offsetting the underdamping of central
      origin. Owing to the dual effect of nasal CPAP on the upper airway and
      respiratory pump, use of nasal CPAP can also effectively reduce the plant gain,
      accounting for the therapeutic effect of nasal CPAP on the central sleep apnea.

PMID- 8295429
TI  - Pleural pressure measured in the zone of apposition of diaphragm to rib cage in
      rabbits.
AB  - In 10 anesthetized adult rabbits, we studied the effect of spontaneous breathing
      and positive pressure ventilation on pleural pressure on the costal lung surface
      (Ppl) and in the zone of apposition of the rib cage to the diaphragm (Papp). Ppl
      and Papp were measured by rib capsules installed in the 5th or 6th rib and 11th
      or 12th rib, respectively. Esophageal (Pes) and gastric (Pga) pressures were
      measured with air-filled balloons. At end expiration (functional residual
      capacity), Ppl was subatmospheric (-2.5 +/- 1.4 cm H2O), decreased during
      spontaneous inspiration, and was in phase with Pes. In contrast, Papp was above
      atmospheric pressure (2.1 +/- 1.8 cm H2O), increased during inspiration, and was
      in phase with Pga. Papp lagged Ppl by 180 degrees during spontaneous inspiration
      but was in phase with Ppl during mechanical ventilation. Changes in Ppl (delta
      Ppl) during inspiration were greater in magnitude than either delta Papp or delta
      Pga. Changes in transdiaphragmatic pressure in the zone of apposition (delta Pga
      delta Papp) were near zero (-0.4 +/- 0.3 cm H2O), much smaller in magnitude than
      those (delta Pga-delta Ppl) associated with the lung (3.0 +/- 1.5 cm H2O). These
      results are consistent with the concept that during breathing, abdominal pressure
      is transmitted to the zone of apposition of the rib cage to the abdomen. During
      spontaneous breathing at rest, the pleural space in the zone of apposition is
      mechanically independent of the pleural space associated with the lung.

PMID- 8295430
TI  - Alpha 1-adrenergic and muscarinic receptors in adult and neonatal rat type II
      pneumocytes.
AB  - Binding characteristics of the alpha 1-adrenergic radioloigand [3H]prazosin, and
      the muscarinic cholinergic radioligand, [3H]quinuclidinyl benzilate, were
      determined both in intact cell preparations of rat alveolar type II pneumocytes
      (TIIPs) and in membrane preparations of rat lung tissue. Binding in adult and
      neonatal (< 24 h postnatal age) rats was also compared. Binding affinities for
      both receptor classes on TIIPs and whole lung membrane preparations alike did not
      vary significantly with age. In lung membrane preparations, the concentrations of
      both receptor classes were higher in neonates than adults. In TIIPs, the alpha 1
      adrenergic receptor concentration was higher in neonates, but muscarinic receptor
      concentration was higher in adults. To begin investigation of the functional
      significance of these receptors, the effects of alpha 1-adrenergic and muscarinic
      agonists on intracellular calcium ion concentration ([Ca2+]i) were also measured.
      Both agonists induced consistent increases in [Ca2+]i, which were blocked by
      respective antagonists. These data indicate the presence of receptors on TIIPs
      for alpha 1-adrenergic and muscarinic agonists that may influence cellular
      function via modulation of [Ca2+]i.

PMID- 8295432
TI  - Airway dysfunction in patients with Parkinson's disease.
AB  - To investigate pulmonary function abnormalities in Parkinson's disease (PD), we
      obtained maximal inspiratory and expiratory flow-volume curves in 63 patients (59
      under treatment) with different stages of the disease, not filtered for
      respiratory symptoms. PD severity was evaluated by the Unified PD Rating Scale,
      the Webster's scale, and Hoehn and Yahr staging. Patients with more severe PD had
      lower percentage forced vital capacity (FVC%), and peak inspiratory and
      expiratory flows. Those with fluctuations and/or dyskinesias had lower FVC% and
      percentage forced expiratory flow volume in 1 sec (FEV1%). There were a number of
      weak but significant correlations between PD scales and spirographic parameters.
      Thirty one patients (49.2%) had pathological flow-volume curves. The clinical
      profile and the duration of the disease did not influence the pattern of the
      curve. Physiologic evidence of upper airway obstruction was observed in 3 cases.
      A spirometric restrictive ventilatory defect (FEV1/FVC higher than or equal to
      80%) was observed in 54 patients (85%), while generalized airway obstruction was
      present only in one nonsmoker. We conclude that abnormal flow-volume loop contour
      is a frequent finding in PD. This probably reflects involvement of the upper
      airway musculature, that in some patients can produce upper airway obstruction.
      Generalized airflow limitation is not an important characteristic of PD. By
      contrast, a restrictive spirometric defect, probably due to incoordinated
      expiratory effort or abnormally low chest wall compliance, is the main
      spirometric finding in these patients.

PMID- 8295431
TI  - Messenger RNA levels of lung extracellular matrix proteins during ozone exposure.
AB  - Continuous exposure of rats to ozone has been shown to result in lung epithelial
      damage, inflammation, and subsequent increases in collagen content. The main goal
      of this study was to identify the earliest time point of altered extracellular
      matrix protein gene expression by utilizing Northern blot analyses of rat lungs
      continuously exposed to 1.0 ppm ozone for 14 days. An early increase of steady
      state fibronectin mRNA levels was observed at 2 days of exposure, prior to the
      time point of increased type I collagen mRNA, which was seen at 4 days. This
      increased level of type I collagen mRNA preceded measurable changes in total lung
      collagen content, observed at 7 days. In addition, peak levels of the growth
      related proto-oncogene c-myc mRNA could be correlated with maximal increases of
      lung DNA content, although the initial increase in c-myc mRNA preceded measurable
      changes of total lung DNA. The use of specific cDNA probes for measuring altered
      gene expression can be useful for defining the early cellular and molecular
      events in ozone-induced lung injury.

PMID- 8295433
TI  - Implications of the dielectrical behaviour of human blood for continuous online
      measurement of haematocrit.
AB  - A study was designed to explore the possibility of detecting the haematocrit of
      blood by means of admittance measurements. The admittance and phase angle of
      blood kept in a measuring cell were determined at various frequencies between 60
      kHz and 24 MHz. A reliable and accurate estimation of haematocrit was obtained in
      two ways. First, low-frequency admittance, high-frequency admittance and a factor
      x, which was the conductive percentage of cell content, were used. Secondly, the
      maximum phase angle was used. Both methods can be applied to obtain continuous on
      line information about haematocrit for blood volume control during haemodialysis.

PMID- 8295434
TI  - Isotonic length/force models of nine different skeletal muscles.
AB  - The isotonic length/force relationships of nine skeletal muscles in the cat's
      hindlimb were determined using electrical stimulation of the sciatic nerve
      branches. Large variability in the active, passive, total force patterns and
      elongation ranges was found. The lateral gastrocnemius (LG), medial gastrocnemius
      (MG), peroneus longus (PL), flexor digitorum longus (FDL), tibialis posterior
      (TP) and soleus (Sol) showed symmetric active force curves, whereas those of the
      extensor digitorum longus (EDL), tibialis anterior (TA) and peroneus brevis (PB)
      were asymmetric. The total force curves of the EDL, LG, MG, FDL, TP and Sol
      increased quasilinearly through the elongation range, whereas the PL and PB
      increased in a nonlinear fashion. The TA had an intermediate plateau. The ranges
      were generally asymmetric, with a longer shortening range than lengthening past
      the optimum length. A simple model of the active force was fitted to all except
      the MG, EDL and TA, which are complex, with at least two compartments. These were
      successfully fitted with a two-compartment model. The variabilities encountered
      in the various isotonic length/force curves confirm the need to represent muscles
      according to their architecture to account for the variety of properties
      exhibited, which reflect their adaptations to their functions.

PMID- 8295435
TI  - Application of finite-element analysis with optimisation to assess the in vivo
      non-linear myocardial material properties using echocardiographic imaging.
AB  - An application of finite-element analysis with an optimisation technique to
      assess the myocardial material properties in diastasis in vivo is described.
      Using the data collected from an animal model, the three-dimensional geometry of
      the left ventricular chamber, at several times in diastole, was reconstructed.
      From the measurement of the ventricular chamber pressure during image
      acquisition, finite-element analysis was performed to predict the expansion
      during diastasis. Initially, by restricting the motion of the epicardial nodes
      and computing the reaction forces, an 'equivalent pericardial pressure' was
      determined and applied in subsequent analysis. The duration of diastasis was
      divided into three or four intervals and the analysis was performed at each
      interval to assess the material properties of the myocardium. Using such a step
      wise linear approach, the non-linear material properties of the myocardium during
      passive expansion was determined. Our results demonstrated that the computed
      'equivalent pericardial pressure' increased with and was smaller than the
      corresponding left ventricular chamber pressure. The passive myocardium exhibited
      a linear tangent modulus against chamber pressure relationship which is
      equivalent to an exponential stress/strain relationship, similar to those
      suggested by in vitro studies.

PMID- 8295436
TI  - Effect of compliance on a time-domain estimate of the characteristic impedance of
      the pulmonary artery during acute pulmonary hypertension.
AB  - In 11 pigs under general endotracheal anaesthesia, the time-domain method of
      determining the pulmonary arterial input impedance was compared with the
      frequency-domain equivalent under normal conditions as well as acute pulmonary
      hypertension induced by glass microspheres. The time-domain methods of
      determining the pulmonary arterial compliance C and pulmonary vascular bed
      resistance Rp compared favourably with the frequency-domain equivalents (r =
      0.774, n = 60, p < 0.001 and r = 0.906, n = 60, p < 0.001, respectively), even at
      mean pulmonary artery pressures (MPAP) of 35 mmHg and above. A consistent and
      ever-increasing difference between characteristic impedance Zo(omega), estimated
      by averaging input impedance modulus values over a selected frequency range, and
      its time domain equivalent Ro with increasing MPAP was shown to be the cause of
      the poor fit between the measured and remodelled pulmonary blood flow. By
      analysing a time-domain estimate of the pulmonary characteristic impedance Ro(C,
      Rp, t), it was demonstrated that the characteristic impedance was dependent on C.
      Ro is therefore not an accurate representation of the characteristic impedance,
      especially under conditions of acute pulmonary hypertension. Ro(C, Rp, t) should
      therefore be calculated instead.

PMID- 8295437
TI  - Electrogastrogram simulation using a three-dimensional model.
AB  - The recording of gastric electrical activity using cutaneous electrodes is known
      as electrogastrography, and the recorded electrogastrogram comprises the
      electrical control activity and the contraction-related electrical response
      activity. The electrogastrogram has been simulated using a three-dimensional
      model that takes the effect of inhomogeneities into consideration. The model
      reproduces the electrical control activity and the second component of the
      electrical response activity. Spike activity is not reproduced. The increase in
      amplitude towards the antrum and the phase coupling between various regions is
      reflected in the simulated electrogastrogram. There is a possibility of
      determining the velocity of propagation from the phase difference with electrodes
      located above the antrum.

PMID- 8295438
TI  - Beat-to-beat measurement and analysis of the R-T interval in 24 h ECG Holter
      recordings.
AB  - This study assesses the feasibility of beat-to-beat measurement of the R-T
      interval in Holter ECG recordings. The low sampling rate of the Holter system was
      increased by a specific interpolating filter, and the precision and accuracy of
      two T-wave fiducial point (T-wave maximum: Tm, T-wave end: Te) detection
      algorithms were compared. The results of the validation tests show better
      performance of the Tm measurement procedure in the presence of high noise levels.
      The overall process for the beat-to-beat R-T interval measurement was then tested
      on ECG Holter recordings collected during free and controlled respiration.
      Finally, the R-Tm and the corresponding R-R intervals were measured on 24 h ECG
      recordings of healthy subjects and the spectral analysis was applied to the
      constructed series. Both R-R and R-Tm spectra show two main frequency components
      (low-frequency approximately 0.1 Hz, high-frequency approximately 0.25 Hz)
      changing in their power ratios continuously throughout the 24 h period. The
      method described seems to provide a dynamic index of the sympatho-vagal balance
      at the ventricle that can be useful for a deeper understanding of ventricular
      repolarisation duration variability.

PMID- 8295440
TI  - Time-varying digital filtering of ECG baseline wander.
AB  - Time-varying filtering techniques are applied to the problem of baseline
      correction by letting the cut-off frequency of a linear filter be controlled by
      the low-frequency properties of the ECG signal. The time-varying filter is
      implemented as a bank of linear low-pass filters, in which each filter has a
      slightly differing cut-off frequency. Sampling rate decimation and interpolation
      are employed because the design of a filter for baseline reduction can be treated
      as a narrowband filtering problem. All filters have a linear phase response to
      reduce, for example, ST-segment distortion. The performance of the technique
      presented is studied on ECG signals with different types of simulated baseline
      wander. The results are compared with the performance of time-invariant linear
      filtering and cubic spline interpolation. The results show that an improvement in
      performance can be achieved when using time-varying filtering, especially at low
      heart rates or during episodes with excessive base-line wander.

PMID- 8295439
TI  - Rapid measurement of regional cerebral blood flow in the baboon using 15O
      labelled water and dynamic positron emission tomography.
AB  - The sensitivity and reproducibility of rapid measurements of regional cerebral
      flow (rCBF) using a bolus injection of H2 15O and dynamic positron emission
      tomography (PET) were investigated in anaesthetised baboons. The cerebrovascular
      reactivity to changes in arterial pCO2 was used as an experimental support. PET
      data were acquired over 4 min following a single bolus intravenous injection of
      H2 15O, while arterial blood was withdrawn for continuous activity counting.
      Images were reconstructed with a dynamic sequence of 45 x 2s + 15 x 10s,
      including a correction for decay. Regional values of CBF were derived from non
      linear least-squares fits of the time activity curves using a four-parameter two
      compartment model. The results obtained with a four-parameter fitting method were
      compared with those obtained with two other rapid estimation methods, first
      fitting two parameters only, CBF and partition coefficient (p), and secondly
      autoradiography (with p fixed at 0.95 ml brain ml blood-1). Twelve regions of
      interest were analysed. The values for the basal CBF obtained from 13
      measurements in two baboons were close to published values obtained with other
      techniques. Reproducibility checks showed a mean variation of 9.7 per cent. The
      CBF measurements performed in hypercapnic conditions gave results similar to
      published data in other animal species, showing a 4.5 +/- 0.9 per cent increase
      in CBF per mm Hg paCO2. The results obtained with the three estimation techniques
      were closely correlated. The dynamic bolus H2 15O method appeared to be suitable
      for high blood flow measurements.

PMID- 8295441
TI  - Optimisation of a computer vision system for the interpretation of American Sign
      Language.
AB  - Presented in this paper is a simulation algorithm for the optimisation of camera
      position with respect to the signer, to have a full and reliable interpretation
      of the American Sign Language. The simulation includes a three-dimensional world
      point into two-dimensional image point transformation algorithm, the effect of
      the depth information loss and a sign projection correction test. It is concluded
      that the viewing camera should be positioned at any point in a specified area
      subtended by a solid angle of 30 degrees, where the centre of the area is located
      at 45 degrees in the azimuth and 45 degrees in elevation relative to the signer.
      The theory and the technique are tested with regard to the efficiency of
      interpreting American Sign Language (ASL) by two adult signers. One of the
      signers had been using ASL on a regular basis since infancy, and the second
      signer had signed for the past five years. It is demonstrated that positioning
      the camera anywhere in the specified area provides a 96 per cent correct
      interpretation of the 36 signs tested. The results also provide a preliminary
      indication that signer variability may not present a major problem in
      interpretation, and that a computer vision system which captures the optimum
      depth information can distinguish between signs which, to the naked eye, appear
      to have similar characteristics.

PMID- 8295442
TI  - Multiple-scattering effects in transmission oximetry.
AB  - To develop an algorithm for the spectrophotometric determination of the oxygen
      saturation in blood, a model for the transmission of light in a scattering and
      absorbing medium is developed, taking into account effects of multiple
      scattering. The computed results obtained by a Monte Carlo simulating program
      agreed well with those found by experiment. The results were compared with those
      obtained by the commonly used algorithm of transmission oximetry (based on
      Lambert-Beer's law) and it was found that the calibration curves obtained by this
      method were strongly dependent on the haematocrit and thickness of the sample.
      These curves were less reliable the lower the saturation of oxygen.

PMID- 8295443
TI  - Four-channel ambulatory monitoring system for percussive mechanical trauma to
      industrial workers' hands.

PMID- 8295444
TI  - Preliminary notes on the conversion of three-dimensional images of bones into CAD
      structures for the pre-operative planning of intertrochantheric osteotomies.

PMID- 8295445
TI  - Electro-optical simulator for pulse oximeters.

PMID- 8295446
TI  - Influence of the recognition artefact in automatic analysis of long-term
      electrocardiograms on time-domain measurement of heart rate variability.

PMID- 8295447
TI  - MRI evaluation of the sphenoid sinus after transsphenoidal approach to the
      pituitary.
AB  - The transsphenoidal approach to the pituitary (TSA) is currently the most common
      approach used to treat pituitary tumors. The surgical technique necessitates an
      incomplete stripping of sphenoid sinus mucosa. Long-term postoperative magnetic
      resonance imaging (MRI) evaluation of the sphenoid sinus has not been reported. A
      retrospective review of patients undergoing a TSA at the University of Washington
      Hospitals was performed. Preoperative scans were compared with postoperative
      scans done during three time intervals. Group 1 had scans at 1 to 12 weeks
      postoperatively; 10 of 10 patients had sinus effusions. Group 2 had scans at 6 to
      18 months post-operatively; 22 of 31 had mucosal abnormalities. Group 3 had scans
      at 2 to 3 years; 7 of 9 were abnormal. MRI evaluation indicates that a majority
      of patients have both acute and chronic sphenoid sinus abnormalities after TSA.

PMID- 8295448
TI  - Diagnosing nasopharyngeal cancer.
AB  - When nasopharyngeal carcinoma is suspected clinically, an adequate tissue sample
      should be taken at the patient's first visit. Should the initial tissue sample be
      nondiagnostic, depending on the index of suspicion in the individual case, the
      process may be repeated under either local or general anesthesia. It is important
      that a detailed examination of the nasopharynx be undertaken in the outpatient
      setting. Biopsy should be performed accurately under direct visualization. Large
      biopsy forceps are essential to obtain an adequate tissue sample. Biopsy under
      local anesthesia is safe, easy to perform, well tolerated by the patient, and
      should be undertaken in the outpatient clinic. This direct diagnostic approach
      achieves a rapid diagnosis in patients with nasopharyngeal carcinoma.

PMID- 8295449
TI  - Restoration of anterior mandible with the free fibula osseocutaneous flap.

PMID- 8295450
TI  - Redundant supraglottic mucosa in association with obstructive sleep apnea.

PMID- 8295451
TI  - Preliminary data on the effect of pharyngeal flaps on the upper airway in
      children with velopharyngeal inadequacy.
AB  - Seven patients who received pharyngeal flaps for velopharyngeal incompetence
      (VPI) were studied to assess the effect of the procedure on nasal airway size.
      The findings suggest that the pharyngeal flap does not significantly decrease the
      upper airway in all patients. The effect of the flap did not correlate with the
      type of cleft, and was most pronounced in the inspiratory phase of the breathing
      cycle. Reasons for this variable effect, assumed to be related to an already
      impaired nasal airway in most cleft patients, are discussed.

PMID- 8295452
TI  - Sulcus vocalis in laryngeal cancer: a histopathologic study.
AB  - The incidental finding of sulcus vocalis in surgical specimens of patients with
      laryngeal cancer prompted this review. Sulcus deformities were histologically
      identified in 28 (48%) of 58 whole-mount coronal serial-sectioned laryngeal
      specimens procured from laryngeal cancer patients. The lesions were analyzed,
      described, and graded. A control group of 20 larynges, obtained from autopsies of
      patients without known laryngeal pathology, were similarly processed, and whole
      mount histologic sections were studied. Four of these specimens (20%) also
      demonstrated sulcus deformities. In the control group, the shape and location of
      the sulci were similar, but the lesions were smaller than in the cancer group.
      The sulcus lesions revealed chronic inflammation of the subepithelial tissues
      with vascular ingrowth and fibrosis of the superficial lamina propria (Reinke's
      space); in the cancer group the sulcus was usually on the opposite vocal fold,
      where irritation from the tumor might be anticipated. Although the etiology of
      the sulci remains controversial, these findings suggest that irritation and
      inflammation might play a role in the pathogenesis of sulcus vocalis.

PMID- 8295453
TI  - The effect of unilateral chorda tympani damage on taste.
AB  - Patients with localized damage to the taste system often experience no subjective
      change in real-world taste experience. In an effort to understand this, eight
      patients who recently underwent acoustic neuroma removal were evaluated for taste
      loss. Localized taste testing showed that taste intensities decreased in the
      distribution of cranial nerve VII ipsilateral to tumor removal as expected, but
      asymmetries occurred for IX. Intensities were greater on the side contralateral
      to the tumor removal. In addition, palatal taste, also thought to be mediated by
      VII, was not totally abolished. It is concluded that cranial nerve IX is normally
      inhibited by cranial nerve VII in the taste network. When VII is damaged, this
      inhibition is abolished. This release of inhibition serves as a compensation
      mechanism that preserves normal taste experience.

PMID- 8295454
TI  - Treatment of adductor laryngeal breathing dystonia with botulinum toxin type A.
AB  - Adductor laryngeal breathing dystonia (ALBD) is a rare disorder in which patients
      have persistent inspiratory stridor, usually normal voice, and cough. Physical
      exam is characterized by paradoxical movement of the vocal cords on inspiration.
      These patients have involuntary action-induced spasms of the adductor laryngeal
      muscles on inspiration. There has been no uniformly satisfactory treatment for
      the disease. Speech therapy, psychotherapy, and pharmacotherapy have all had
      limited success. We report the successful use of botulinum toxin type A in seven
      patients with adductor laryngeal breathing dystonia. All patients received
      bilateral thyroarytenoid injections. All patients had toxin effect within 72
      hours, reaching maximal effect within 2 weeks with sustained improvement for an
      average of 13.8 weeks. Adverse effects included breathy voice and mild choking on
      liquids. Both resolved, on average, within 2 weeks. This retrospective study
      supports the safe and effective use of botulinum toxin type A in the treatment of
      adductor laryngeal breathing dystonia.

PMID- 8295455
TI  - Cerebrospinal fluid leak following acoustic neuroma removal.
AB  - Cerebrospinal fluid (CSF) leak has been a constant and unresolved complication of
      acoustic tumor surgery. This study retrospectively reviews 381 primary acoustic
      tumor surgeries performed by a single, senior, neurotologist and neurosurgeon
      team from 1979 through 1991. There were 68 cerebrospinal fluid leaks in 66
      patients (66/381; 17%). There was no significant difference in the incidence of
      CSF leak between the translabyrinthine group (21%) and the retrosigmoid
      transmeatal group (16%). Translabyrinthine leaks were evenly divided between
      rhinorrhea and the postauricular wound while retrosigmoid transmeatal leaks were
      predominantly rhinorrhea. Eleven of 14 translabyrinthine wound leaks responded to
      pressure dressing and suture. The remaining 3 ceased with continuous lumbar
      cerebrospinal fluid drainage. Ten of 14 cases of translabyrinthine rhinorrhea
      responded to continuous lumbar cerebrospinal fluid drainage, and those in whom it
      failed were cured with revision of the mastoidectomy/labyrinthectomy cavity.
      Twenty-one of 28 cases of retrosigmoid transmeatal rhinorrhea responded to
      continuous lumbar cerebrospinal fluid drainage, and those in whom it failed were
      cured with extracranial, transmastoid revision. The incidence of cerebrospinal
      fluid leak was not influenced by age, sex, size of tumor, postoperative
      hydrocephalus, or the intraoperative use of autologous fibrin glue. Meningitis
      was an unusual complication, occurring in 3% of all patients.

PMID- 8295456
TI  - Otitis media with effusion in head and neck cancer patients.
AB  - Fifty-two patients who had otitis media with effusion associated with head and
      neck malignancies were identified and studied retrospectively. Forty-three of the
      patients underwent myringotomy and tube for treatment of the effusion. Ten (23%)
      of the 43 patients had either multiple infections or continuous otorrhea
      necessitating tube removal. The patients identified as having the highest rate of
      serious complications following myringotomy and tube were those individuals who
      had nasopharyngeal carcinoma, with 6 (55%) of 11 patients in this group having
      suffered major infections during the study. Myringotomy and tube is a
      satisfactory treatment for most patients who have effusions as a result of non
      malignant etiologies; however, infections were more common and more severe in the
      study group than those anticipated in noncancer patients. Expectant management
      and the use of amplification in selected cases may prove to be a viable
      alternative in patients with unilateral effusion and/or relatively mild symptoms.

PMID- 8295457
TI  - Tracheostomal stenosis after total laryngectomy: an analysis of predisposing
      clinical factors.
AB  - Stenosis of the terminal tracheostome is a distressing complication of total
      laryngectomy. A retrospective analysis of 207 patients who underwent total
      laryngectomy is presented; an overall incidence of tracheostomal stenosis of 13%
      is reported. The incidence of tracheostomal stenosis is higher in females (26%),
      patients having immediate tracheoesophageal puncture (19%), pectoralis major
      myocutaneous flap pharyngeal reconstruction (26%), and tracheostomal infection
      (50%) which is shown to be significant (P < .05). However, on multivariate
      analysis, only female sex and tracheostomal infection are independent
      determinants. Recognition of these clinical factors identifies patients at
      increased risk of developing this complication and thus allows appropriate
      perioperative planning to minimize its incidence.

PMID- 8295458
TI  - Langerhans' cell histiocytosis in childhood: management of head and neck
      manifestations.
AB  - The authors carried out a retrospective analysis of 131 cases of Langerhans' cell
      histiocytosis treated at two centers over a 30-year period. All those with head
      and neck manifestations have been reviewed with particular reference to
      management and outcome. The role of chemotherapy, radiotherapy, and surgery is
      discussed, and we present our results of the successful introduction of topical
      nitrogen mustard (Mustine) ear drops for meatal skin involvement. During the
      period of the study our modus operandi has evolved from an aggressive medical and
      surgical approach, favored early in the series, to our present more conservative
      approach, with an attendant reduction in morbidity.

PMID- 8295459
TI  - Endoscopic treatment of supraglottic and hypopharynx cancer.
AB  - Transoral excision of supraglottic and hypopharynx cancer as a single modality is
      effective when lesions are selected for small size and endoscopic accessibility.
      Excisional biopsy with clear margins of larger supraglottic tumors in combination
      with postoperative radiotherapy provides an excellent treatment alternative for
      selected lesions in patients who are not candidates for open surgery. In this
      preliminary report, 45 cases using this minimally invasive approach are reviewed
      outlining oncologic rationale and functional advantages. A large bore tubed
      laryngoscope or the adjustable bivalve supraglottiscope was used along with a
      carbon dioxide laser in all cases. In 22 of the 45 patients (mostly T1), local en
      bloc excision of the primary cancer was performed as sole treatment on selected
      lesions of the supraglottis and hypopharynx. There were no local recurrences,
      however, 1 patient developed a neck recurrence and was salvaged by neck
      dissection. Twenty-three of the 45 patients had more extensive primaries (mostly
      T2, T3) and N0 necks. Transoral excisional biopsy was followed by full-course
      radiation therapy to the primary site and both necks. All 23 were followed a
      minimum of 2 years, and the median follow-up period was 58 months. Clear margins
      were obtained in 16 of 23, and there were no recurrences in the larynx. Two of 16
      did fail in the neck and died despite neck dissection. Seven of 23 patients had
      positive margins and, despite full-course radiotherapy to the primary site and
      both necks, 5 of 7 failed locally or regionally. Two of the 7 died of their
      disease despite open salvage surgery. Therefore, 4 of 23 patients who underwent
      transoral excision of larger lesions followed by full-course radiotherapy died of
      recurrent cancer.

PMID- 8295460
TI  - The Vienna Cochlear Implant in patients with obliteration of the cochlea.
AB  - Twelve deaf patients with obliterated or ossified cochleas received the
      extracochlear version of the Vienna Cochlear Implant. Four patients, 1 of them a
      child, developed open speech comprehension. Obliteration of the cochlea could not
      always be predicted by conventional tomography of the temporal bone. Short
      duration of deafness, wide dynamic range, and good ability of time resolution
      (small temporal difference limen [TDL]) are predictors for good postoperative
      results. Obliteration or ossification of the cochlea per se is no
      contraindication to cochlear implantation.

PMID- 8295461
TI  - Measurement of laryngeal resistance in the evaluation of botulinum toxin
      injection for treatment of focal laryngeal dystonia.
AB  - In the past, there has been no consistent, objective method of following patients
      undergoing botulinum toxin injections for treatment of laryngeal dystonia.
      Herein, the application of translaryngeal resistance measurements to 15 dysphonic
      patients is described. Laryngeal resistance is calculated from analysis of
      translaryngeal pressure and airflow during the utterance /pi/, and found to fall
      predictably after successful toxin injection. In our series of patients,
      laryngeal resistance dropped by 69.1% after initial toxin injection. The changes
      in resistance over time correlate with subjective impressions of voice quality.
      Translaryngeal resistance measurements can be used objectively to follow patients
      longitudinally after injection and to collect objective data for analysis. No
      previously described measurements have met all these criteria. Laryngeal
      resistance measurement is an ideal method of documenting the results of botulinum
      toxin injection for the treatment of focal laryngeal dystonia.

PMID- 8295462
TI  - Eustachian tube compliance in cleft palate--a preliminary study.
AB  - With the use of the tubal compliance test and the forced response test (FRT), the
      compliance and ventilatory functions of the eustachian tube (ET) were examined in
      19 children with otitis media with effusion (OME) and cleft palate, in 31
      children with OME but without cleft palate, and in 19 individuals with traumatic
      perforation of the eardrum without history of other otological disease
      (controls). The tubal compliance results in the group with both cleft palate and
      OME were significantly higher than the results obtained with the controls, but
      did not differ significantly from the results obtained with the patients with OME
      but without cleft palate; this indicated that the ETs of those patients with OME
      and cleft palate, and the ETs of those patients with OME but without cleft
      palate, appeared to be more collapsible than the ETs of normal subjects. It was
      speculated that such an aerodynamic property of the ET observed in the group with
      OME and cleft palate and in the group with OME but without cleft palate may be
      due mainly to possible inflammatory condition of the tubal mucosa rather than to
      abnormal anatomy or to an abnormal physical property of the framework (such as
      cartilage) of the ET.

PMID- 8295463
TI  - Surgical variables affecting postoperative swallowing efficiency in oral cancer
      patients: a pilot study.
AB  - This study examined the correlation between swallow function at 3 months
      postoperatively and surgical variables including volume resected, flap volume,
      ratio of flap volume to volume resected, percentage of oral tongue, tongue base,
      and anterior and lateral floor of mouth resected, and whether or not the mandible
      was preserved in 30 surgically treated oral cancer patients. Swallows of measured
      amounts of liquid and paste (pudding) materials were examined
      videofluoroscopically. Nine measures of swallow function were completed for each
      swallow. A factor analysis of all swallow variables was done for liquid and for
      paste consistencies to determine whether one measure was statistically
      representative of all swallow measures. This analysis indicated that oral
      pharyngeal swallow efficiency (OPSE) represented all measures for both liquid and
      paste consistencies. Then the correlation between OPSE and surgical variables was
      defined. Only percentage of oral tongue and percentage of tongue base resected
      were significantly negatively correlated with OPSE. That is, OPSE decreased for
      both liquid and paste as percentage of oral tongue or percentage of tongue base
      resected increased. Results are discussed in terms of diet choices and surgical
      management.

PMID- 8295464
TI  - Epstein-Barr virus lytic cycle spreads via cell fusion in a nasopharyngeal
      carcinoma hybrid cell line.
AB  - NPC-KT cl.S61, a subclone derived from an epithelial-nasopharyngeal carcinoma
      hybrid cell line NPC-KT, showed extensive Epstein-Barr virus (EBV) production and
      cell fusion when the EBV replicative cycle was induced by 5-iodo-2'-deoxyuridine.
      On the contrary, parental NPC-KT cells produced virus at a lower level and did
      not show cell fusion. Cell fusion in cl.S61 cells was blocked by 2-deoxyglucose
      and acyclovir, inhibitors of glycosylation and EBV DNA polymerase, respectively,
      with a concomitant decrease in the number of cells expressing EBV growth
      associated antigens. However, the frequency of virus antigen expression in
      parental NPC-KT cells was not significantly affected by these drugs. This result
      suggests that efficient production of EBV from cl.S61 cells is due to the
      spreading of viral replicative cycle via cell fusion. It was also demonstrated by
      in situ autoradiography that cl.S61 cells producing virus fused to not only EBV
      receptor/CR2 positive Raji and BJAB cells, but also to receptor-negative Jurkat
      cells. The possible mechanism of EBV entry into cells devoid of virus receptor by
      cell fusion is discussed.

PMID- 8295465
TI  - Blood transfusion and other prognostic variables in the survival of patients with
      cancer of the head and neck.
AB  - The clinical records of 207 patients with squamous cell carcinoma of the head and
      neck, diagnosed and surgically treated at the Otolaryngology Division of
      Pordenone General Hospital and Aviano Cancer Centre, northeast of Italy, from
      January 1982 to December 1987, were retrospectively reviewed to gather
      information on blood transfusions and other characteristics potentially related
      to survival. The group of patients (mean age = 59 years) included 85 cases (41%)
      of laryngeal cancer, 80 cases (39%) of oropharyngeal and hypopharyngeal cancer,
      and 34 cases (16%) of cancer of the oral cavity. Fifty-five patients (27%) did
      not receive any blood transfusion while 152 patients were transfused with
      different amounts of blood. At the univariate analysis, nodal involvement,
      clinical stage, type of therapy, status of surgical margins, and metastatic
      spread beyond the nodal capsule appeared to be significantly linked to prognosis.
      After adjustment for other prognostic variables, transfused patients showed a
      twofold higher hazard ratio as compared to nontransfused patients, but such an
      unfavorable predictive value should be evaluated in the context of the other
      prognostic correlates of cancer of the head and neck.

PMID- 8295466
TI  - Human papillomavirus types 11 and 16 detected in nasopharyngeal carcinomas by the
      polymerase chain reaction.
AB  - Most nasopharyngeal carcinomas (NPCs) are of the nonkeratinizing or
      undifferentiated types, which are consistently associated with Epstein-Barr virus
      (EBV). The smaller group of highly differentiated, keratinizing NPCs seems to be
      only infrequently associated with EBV. In order to examine whether these rare
      tumors were related to another oncogenic virus, the authors used the polymerase
      chain reaction to examine paraffin-embedded sections of 15 keratinizing NPCs for
      human papillomavirus (HPV) types 6, 11, 16, and 18 genomic sequences. HPV DNA was
      found in 4 tumors (1 HPV-11-positive, and 3 HPV-16-positive tumors). None of 23
      undifferentiated or nonkeratinizing NPCs harbored HPV DNA. The putatively
      oncogenic HPV type 16 may thus be involved in the carcinogenesis of some EBV
      negative keratinizing squamous cell nasopharyngeal carcinomas.

PMID- 8295467
TI  - Effects of 830 nm continuous wave laser diode irradiation on median nerve
      function in normal subjects.
AB  - The presence, magnitude, and nature of the effect that low intensity laser
      irradiation has on nerve function, growth, and repair constitute a contentious
      area of research. We have addressed one aspect of this controversy by
      systematically examining the influence of 830 nm laser radiation on median nerve
      function. In particular, we investigated median nerve motor and sensory distal
      latencies, action potential amplitudes, action potential areas, and conduction
      velocities as well as dorsal hand skin temperatures in 33 normal subjects in a
      double-blinded, randomized controlled study. All subjects received identical
      treatment: 30 seconds of "irradiation" at 10 points over the course of the right
      median nerve (five sites on the forearm and five sites distal to the wrist
      crease) with either an active (1.2 J/point) or inactive (0 J/point) 40 mW 830 nm
      continuous wave IR laser diode. Latencies, conduction velocities, amplitudes,
      areas, and skin temperatures were collected bilaterally at a baseline immediately
      prior to irradiation and at intervals of 1, 5, 10, 15, 20, and 30 minutes
      following treatment. Analysis of the results reveals that motor and sensory
      distal latencies were decreased in the treated limbs of the laser-treated group
      relative to the control group by 3-4% (P < .016 and .046, respectively, rank sum
      test). No significant differences in these quantities were found between the
      limbs within either group. Similarly, no alterations of action potential
      amplitudes, action potential areas, forearm conduction velocities, or skin
      temperatures were detected within or between the groups.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8295468
TI  - Effect of irradiation by semiconductor laser on responses evoked in trigeminal
      caudal neurons by tooth pulp stimulation.
AB  - The effect of irradiation with a gallium-aluminum-arsenide semiconductor laser on
      responses evoked in trigeminal subnucleus caudal neurons by tooth pulp
      stimulation was investigated electrophysiologically in Wistar rats anesthetized
      with urethane plus alpha-chloralose. The pulp of lower incisor was electrically
      stimulated and the evoked action potentials were extracellularly recorded in the
      ipsilateral caudal neurons. The laser beam was applied on the cervical surface of
      the stimulated incisor. The rate of firing discharges and the numbers of spikes
      evoked in the caudal neurons were compared before and after laser irradiation.
      Laser irradiation suppressed the late discharges in the response of the caudal
      neurons which were evoked by excitatory inputs from C-fiber afferents, but did
      not suppress the early discharges evoked by inputs from A delta-fiber afferents.
      This indicates that low power laser irradiation (semiconductor laser: 830 nm, 350
      mW, CW, through the tooth structures, for 120 s) inhibited the excitation of
      unmyelinated fibers of the pulp without affecting fine myelinated fibers. These
      results suggest that low power laser irradiation has a suppressive effect on
      injured tissue by blocking the depolarization of C-fiber afferents.

PMID- 8295469
TI  - Dose and temporal parameters in delaying injured optic nerve degeneration by low
      energy laser irradiation.
AB  - Low-energy laser irradiation has been reported to postpone the degenerative
      processes in crushed optic nerves of rats, which are part of the nonregenerable
      mammalian central nervous system. In the present study, we evaluated the optimal
      irradiation parameters for this purpose. Optic nerves of 141 rats were subjected
      to crush injury and then irradiated through the eye, starting at different points
      of time before or after the injury, for different durations and periods, using
      various intensities of either helium-neon laser or noncoherent infrared light
      (904 nm). The effect was evaluated by measurements of the compound action
      potentials of the nerve segments between the site of injury and the optic chiasm.
      The compound action potential amplitude of the crushed nonirradiated nerves, as
      measured 2 weeks after the injury, was found to be 0.51 +/- 0.30 mV, in contrast
      to 3.10 +/- 1.03 mV measured in 232 normal nerves. Irradiation with a 10.5 mW
      helium-neon laser for 2 and 3 min once a day for 14 consecutive days resulted in
      maximal preservation of action potentials (1.78 +/- 0.72 and 1.95 +/- 0.71 mV,
      respectively). Irradiations beginning immediately prior to the injury were as
      effective as irradiations beginning soon after it. Irradiations for longer than 3
      min or twice a day aggravated the damage. Noncoherent infrared light was
      ineffective or adversely affected the injured nerves. Our experiments suggest
      that optimal delay of posttraumatic optic nerve degeneration in rats is
      attainable with 10.5 mW helium-neon laser irradiations for 2 or 3 min once a day
      for 14 consecutive days.

PMID- 8295470
TI  - In vitro evaluation of ablation parameters of normal and fibrous aorta using
      smooth excimer laser coronary angioplasty.
AB  - A modified excimer laser energy delivery system was used to irradiate 100
      segments of normal and fibrous aorta in vitro. The laser beam was scanned into 8
      fiber bundles consisting of 50 fibers each resulting in a reduction of the
      applied pulse energy. The total repetition rate was increased to 150 Hz in order
      to keep the repetition rate per fiber bundle close to 20 Hz and to minimize
      thermal injury. The results demonstrate that effective ablation (etch rate per 8
      pulses > 2.0 microns) occurred at an energy fluency of 50 mJ/mm2 in both normal
      and fibrous aorta. Tissue damage (carbonization, tissue separation, fissures,
      cracks, and vacuolization) was in a range of 100 +/- 28 to 152 +/- 30 microns for
      normal aorta and in a range of 57 +/- 35 to 110 +/- 39 microns for fibrous aorta.
      We conclude that effective ablation of normal and fibrous human aorta can be
      achieved by the application of smooth excimer laser coronary angioplasty. This
      improvement of excimer laser technology may result in a reduction of shock wave-
      and cavitation-induced damage leading to a reduction of tissue injury. However,
      this awaits further in vitro and in vivo confirmation.

PMID- 8295471
TI  - Ureteroscopic management of transitional cell carcinoma of the ureter using the
      neodymium:YAG laser.
AB  - Ureteroscopy offers an extension of endoscopic diagnosis and treatment to upper
      urinary tract malignancy. Combination of ureteroscopy and the Nd:YAG laser
      permits accurate and effective treatment of ureteral neoplasms. Nine highly
      selected patients, six males and three females, were treated with low grade
      papillary transitional cell carcinomas of the ureter with at least 24 months
      follow-up. Follow-up cytology and IVP have indicated no evidence for disease
      recurrence between the follow-up periods and minimal morbidity to the
      ureteroscopy and laser treatment.

PMID- 8295472
TI  - Cell vitality in cartilage tissue culture following excimer laser radiation: an
      in vitro examination.
AB  - Excimer laser is used for cartilage debridement, although the resulting cell
      damage is yet unclear. For examination of cartilage survival after treatment, we
      used short-term tissue cultures of human joint cartilage. Specimens were treated
      with a XeCl-Excimer laser using different laser parameters, pulse energies, and
      repetition rates. Following treatment, discs were cultured for 8 days prior to
      examination. In contrast to the 20 microns damage zone as instant visible effect
      in histomorphologic examinations, we found a 0.3 mm zone in which approximately
      50% of cartilage cells had morphological signs of damage on light microscopic
      examinations. Autoradiography revealed that cartilage cells in an 0.5-0.7 mm area
      surrounding the laser craters had no collagen synthesis. This examination
      indicates that cell damage of excimer laser is higher than expected from prior
      studies.

PMID- 8295474
TI  - Study of the fluorescence properties of normal and neoplastic human cervical
      tissue.
AB  - Fluorescence excitation-emission matrices (EEMs) were obtained in vitro for 18
      cervical biopsies from 10 patients. At all excitation emission maxima, but
      especially at 330 nm excitation, 385 nm emission, the average normalized
      fluorescence intensity of histologically normal tissue is greater statistically
      than that of histologically abnormal tissue. A diagnostic algorithm based on the
      relative intensity at 330 nm excitation, 385 nm emission can differentiate
      histologically normal and abnormal biopsies with a higher sensitivity (89%), but
      a lower positive predictive value (67%) and specificity (44%) than colposcopy
      (78%, 88%, 89%, respectively). However, paired comparison of histologically
      normal and abnormal biopsies from the same patient results in a sensitivity of
      75%, positive predictive value of 86% and specificity of 88% for spectroscopic
      identification of histologic abnormality similar to that of colposcopy. This
      pilot study indicates that fluorescence spectroscopy may be useful in
      differentiating normal and abnormal tissue; based on these results, a strategy
      for in vivo studies is discussed.

PMID- 8295473
TI  - Ablation of polymethylmethacrylate by Ho:YAG, Nd:YAG, and Erb:YAG lasers.
AB  - Ho:YAG, Nd:YAG, and Erb:YAG laser ablation of Polymethylmethacrylate (PMMA) was
      investigated under in vitro and simulated clinical conditions. Ablation rates
      were measured for all lasers and after ablation, macroscopic and microscopic
      appearance of the ablation site was investigated. The mean ablation rates of the
      Erb:YAG, Ho:YAG, and Nd:YAG laser increased from 8 microns per pulse at 100 mJ to
      44 microns per pulse at 300 mJ from 100 microns per pulse at 200 mJ to 222
      microns per pulse at 800 mJ and from 28 microns per pulse at 100 mJ to 189
      microns per pulse at 800 mJ, respectively. Macroscopic investigation exhibited
      melting of bone cement for the Ho:YAG and Nd:YAG lasers and pulse-to-pulse
      vaporization for the Erb:YAG laser. The width of thermal alteration, however, was
      comparable for all lasers used. Removal of cement from bone specimens under
      simulated clinical conditions showed good detachment of cement when the fiber was
      used parallel; in case of perpendicular use, remainders of cement and
      carbonization of bone could be observed upon histological investigation.

PMID- 8295475
TI  - Selecting source locations in multifiber interstitial laser photocoagulation.
AB  - A theoretical basis and practical algorithm are described for selecting optimal
      fiber source locations in multifiber interstitial laser photocoagulation (ILP).
      By analyzing the shape of overlapping coagulation patterns, the optimal
      separation of adjacent point heat sources inside a flat target volume boundary is
      shown to be d* = 2 square root of 2rc, where rc is the coagulation radius of a
      single source. Against a curved boundary, the algorithm specifies how d* should
      be altered. To assess the validity of the theory, ILP was conducted in bovine
      muscle by delivering 1064 nm laser energy through two or four plane-cut optical
      fibers simultaneously. Delivered power, exposure duration, and source separation
      were varied. The observed coagulation patterns matched the theory-predicted
      patterns at delivered powers of 1.60W and 1.85W, but not at 2.40W. Also, the
      experiments indicate that reciprocity of delivered power and exposure duration is
      invalid for ILP.

PMID- 8295476
TI  - Tolerance of small bowel anastomoses in rabbits to photodynamic therapy with
      dihematoporphyrin ethers and 630 nm red light.
AB  - Photodynamic therapy (PDT) is being evaluated in experimental clinical trials in
      patients with peritoneal malignancies. Some patients require partial small bowel
      resection with re-anastomosis prior to PDT because of bulky tumor or focal
      involvement of the small bowel by tumor. To assess the safety of PDT in this
      setting, the tolerance of small bowel anastomoses in New Zealand white rabbits to
      PDT with dihematoporphyrin ethers (DHE) and 630 nm light was studied. With
      conventional DHE doses of 1.5-2.5 mg/kg given 24 hours prior to surgery and light
      doses of 0-20 J/cm2 of 630 nm light, no adverse effects were seen on the healing
      of small bowel anastomoses. Higher photosensitizer doses of 10 mg/kg and 20 mg/kg
      in conjunction with 20 J/cm2, however, induced failure and breakdown of fresh
      anastomoses in 2/3 and 4/4 animals, respectively.

PMID- 8295477
TI  - Effect of radiation therapy and Photofrin on tissue response in a rat model.
AB  - Treatment of advanced carcinomas of the head and neck may benefit from adjuvant
      photodynamic therapy and brachyradiotherapy. To date, however, there has been no
      controlled study to evaluate whether high-dose irradiation can be safely
      accomplished without major tissue reaction in the presence of high circulating
      doses of Photofrin, the photosensitizing agent used in photodynamic therapy.
      Thirty adult male white rats were involved in the study. Fifteen rats received
      Photofrin 5 mg/kg intravenously, and 15 rats received the same volume of sterile
      saline intravenously. At 48 hours following injection, each rat received 1,000
      cGy of radiation to a 3 x 5 cm area of dorsal skin using a cobalt linear
      accelerator unit. Skin changes postradiation were observed for degree of
      erythema, blistering, necrosis, and sloughing. Five rats from the Photofrin and
      control radiation groups were sacrificed on days 2, 7, and 21 postradiotherapy.
      Skin changes in each animal were identical with mild erythema lasting from 10-14
      days postradiotherapy. There was no evidence of blistering, necrosis, or
      sloughing of skin in any of the animals studied. Histologic evaluation of the
      irradiated skin after sacrifice demonstrated no difference between the Photofrin
      and saline-irradiated groups. As well, the histologic recovery from acute
      radiation injury was also identical. This controlled study demonstrates that
      radiation therapy may be safely administered without increased morbidity when
      tissue concentrations necessary to perform photodynamic therapy are present.

PMID- 8295478
TI  - Clinical exacerbation of systemic lupus erythematosus after photodynamic therapy
      of laryngotracheal papillomatosis.
AB  - Photodynamic therapy was used to treat a patient with recurrent laryngotracheal
      papillomatosis who had a history of systemic lupus erythematosus (SLE). At the
      time of photoactivation, the patient's SLE was in remission for 2 years.
      Postoperatively, the patient was not compliant in avoiding sunlight exposure and
      developed photosensitive skin reactions of his face and hands. In addition, he
      had clinical activation of his SLE following that exposure.

PMID- 8295479
TI  - Fundus laser coagulation using a video system of scanning laser ophthalmoscope.
AB  - We modified a scanning laser ophthalmoscope for simultaneous photocoagulation of
      the retina and video recording. Using a diode laser (810 nm wavelength), we
      produced fundus lesions that scarred within 14 days.

PMID- 8295480
TI  - Limits of radial time constants to approximate thermal response of tissue.
AB  - The time constant model, as an approximation to the bio-heat equation, was tested
      for non-ablating, deep penetrating (argon) laser beams in absorbing tissue
      phantoms (polyacrylamide) in air. Temperature responses were measured with a
      thermal camera, both during laser irradiation as well as after the laser beam was
      switched off. The radial time constant model was found to give a reasonable
      prediction (within 5%) of temperature rise for irradiation times of up to the
      order of one time constant. The cooling behavior of tissue could not be described
      by one single time constant. The time constant model was found to fit the early
      cooling rate (cooling time about equal to irradiation time) for laser pulse
      durations of up to one time constant. The late cooling rate turned out to be much
      slower than predicted by the radial time constant model, yet it was faster than
      the cooling rate predicted by the one-dimensional instantaneous hot cylinder
      surface model.

PMID- 8295481
TI  - 9-cis-retinoyl-beta-D-glucuronide is a major metabolite of 9-cis-retinoic acid.
AB  - The in vivo metabolism of 9-cis-retinoic acid (9-c-RA), an endogenous ligand of
      retinoid X receptors (RXRs), which can also bind to retinoic acid receptors
      (RARs), was examined in pregnant mice and rats following a single oral dose of
      100 mg 9-cis-retinaldehyde (9-c-RAL)/kg body weight. 9-Cis-retinoyl-beta-D
      glucuronide (9-c-RAG), a metabolite not found in vivo before, was a major
      metabolite of 9-c-RA in mouse plasma and was also present in all mouse tissues
      examined as well as in rat plasma. In both species putative oxidation products of
      retinoic acids and high levels of retinyl esters were found. Concentrations of
      retinoic acid isomers and retinoyl-beta-D-glucuronides in the mouse plasma
      greatly exceeded those of the rat plasma. The finding of high levels of 9-c-RAG
      underlines the importance of glucuronidation in the metabolism of retinoids.

PMID- 8295482
TI  - Effects of a lipopolysaccharide from Pantoea agglomerans on the cocaine-induced
      place preference.
AB  - A lipopolysaccharide from Pantoea agglomerans (LPSp) was purified, and its effect
      on the cocaine-induced place preference was examined in rats. Cocaine (4 mg/kg,
      i.p.) produced a significant place preference. Administration of LPSp (5-1000
      micrograms/kg, i.p.) alone resulted in neither preference nor aversion for either
      the drug- or saline-associated place. However, pretreatment with LPSp (500 and
      1000 micrograms/kg, i.p.) abolished the place preference that had been induced by
      cocaine. Furthermore, treatment with LPSp (500 micrograms/kg, i.p.) abolished
      cocaine (20 mg/kg, i.p.)-induced locomotor enhancement in mice. These results
      suggest that while LPSp itself may possess neither reinforcing nor locomotor
      enhancing effects, it blocks both the reinforcing and the locomotor enhancing
      effects of cocaine. Therefore, LPSp might be useful in pharmacotherapy for
      prevention of recurrent cocaine abuse.

PMID- 8295483
TI  - Isradipine produces neither a conditioned place preference nor aversion.
AB  - Isradipine (ISR) has been reported to block cocaine-induced conditioned place
      preference. Using this procedure, the pairing of this L-type calcium blocker, at
      doses of 2.5, 5.0 and 10 mg/kg, with a preferred (cue-distinct) environment was
      investigated. In a separate experiment, ISR injection (10 mg/kg) was paired with
      the less-preferred environment to determine whether ISR produces a place
      preference. Testing in the non-drugged state revealed that ISR conditioning
      failed to affect side preference in both experiments. The neutral affective
      properties of ISR may be relevant to the development of cocaine use/abuse
      treatment regimens.

PMID- 8295484
TI  - Major role of the renin angiotensin system in the neointima formation after
      vascular injury in guinea pigs.
AB  - ACE inhibition has been shown to prevent neointima formation after vascular
      injury. However, it is not known if this effect is due to a specific inhibition
      of the renin angiotensin system or to another mechanism such as the accumulation
      of bradykinin. In order to answer this question we compared the effects of
      maximal effective doses of cilazapril, an angiotensin converting enzyme (ACE)
      inhibitor, and ciprokiren, a new renin inhibitor, in guinea pigs. Vascular injury
      was induced by endothelial denudation of the right carotid artery of guinea pigs
      treated either by saline (control group), cilazapril (30 mg/kg/day) or ciprokiren
      (24 mg/kg/day). Twelve days after the ballooning, the guinea pigs were
      sacrificed, the carotid arteries were perfused fixed and neointima formation was
      evaluated by quantitative morphometry. Both, ciprokiren and cilazapril prevented
      neointima formation to the same extent (inhibition by 42 and 49%, respectively, p
      < 0.05). These results suggest that, in guinea pigs, renin inhibition prevents
      neointima formation to a similar extent as ACE inhibition. Therefore, ACE
      inhibitors seem to act in this model by inhibiting the renin angiotensin system
      and not by other effects such as accumulation of bradykinin.

PMID- 8295485
TI  - Phenytoin reduces neonatal hypoxic-ischemic brain damage in rats.
AB  - We investigated the possible protective effect of phenytoin on hypoxic-ischemic
      brain damage in neonatal rats. Six-day-old rats underwent ligation of the left
      carotid artery followed by exposure to an 8% oxygen atmosphere for 2.5 hrs. We
      sacrificed the animals 72 hrs later and assessed the hypoxic-ischemic brain
      damage histologically. Phenytoin (50 mg/kg), administered intraperitoneally 1 hr
      before the hypoxia, reduced hypoxic-ischemic infarction in the cerebral cortex
      and striatum, and attenuated neuronal necrosis in the hippocampus. The plasma
      concentration of phenytoin after injection was 11.1 +/- 1.9 micrograms/ml (mean
      +/- S.E.M.) at 1 hr and 22.9 +/- 1.4 micrograms/ml at 4 hrs. Percent volumes of
      the infarction calculated by dividing the sum of damaged areas by the total area
      in serial coronal sections were 79 +/- 3% (mean +/- S.E.M.) in vehicle controls
      versus 13 +/- 6% in phenytoin-treated pups in the cerebral cortex, and 79 +/- 4%
      in vehicle controls versus 12 +/- 5% in phenytoin-treated pups in the striatum.
      We semiquantitatively investigated the hypoxic-ischemic change in 5 hippocampal
      areas: dentate gyrus, CA4, CA3, CA1, and subiculum, in the dorsal hippocampus.
      Pre-hypoxic treatment with phenytoin reduced hypoxic-ischemic damage in all areas
      examined. When phenytoin was administered immediately after the hypoxia, there
      was no difference between vehicle-injected controls and phenytoin-treated pups.
      These results demonstrate that phenytoin can reduce neonatal hypoxic-ischemic
      brain damage.

PMID- 8295486
TI  - [3H]ouabain binding to cultured endothelial cells: effect of cholesterol
      enrichment.
AB  - Binding experiments were performed with [3H]ouabain on cultured human umbilical
      vein endothelial cells (huvEC). Saturation studies yielded a binding capacity
      (Bmax) of 820 +/- 81 fmole/mg pr.(n = 4) and dissociation constant (KD) of 11.7
      +/- 2.1nM (n = 4) in K(+)-free buffer for specific [3H] ouabain binding on these
      cells. External K+ inhibited this binding in a dose-dependent manner. The mean
      value of Bmax is equivalent to about 4 x 10(5) sites per cell, comparable with
      that of smooth muscle cell. These data demonstrated the presence of specific
      [3H]ouabain binding linked to Na+/K+ pump, consistent with the observations of
      ouabain-sensitive 86Rb uptake in huvEC. Effect of cholesterol enrichment was also
      studied. Incubation in media supplemented with cholesterol-phospholipid liposomes
      of molar ratio of 2:1 for 18 hours reduced the Bmax by 31% (P < 0.05) without
      significantly changed the value of KD. This reduction of [3H]ouabain binding
      appeared to be specific for cholesterol since liposome made with pure
      phospholipid did not alter binding. Recent findings indicate that cholesterol
      enrichment and plasma lipoproteins enhance vascular contractile response, our
      results suggest that the cholesterol-enrichment of endothelial cells may also
      indirectly affect the vascular response via disturbing the function of Na+/K+
      pump.

PMID- 8295487
TI  - In vivo and in vitro cocaine modulation on production of cytokines in C57BL/6
      mice.
AB  - In the present study we used both in vivo and in vitro murine models to
      investigate the effects of cocaine on the release of cytokines (IL-1 alpha, IL-6,
      and TNF-alpha by peritoneal macrophages and splenocytes, IL-2, IL-4, IL-5, IL-10,
      and IFN-gamma produced by splenocytes. In vitro cocaine (0.1, 1, 10, 100
      micrograms/ml) exposure inhibited all cytokines produced by ConA-stimulated
      spleen cells and LPS-stimulated macrophages in a concentration dependent manner.
      Different effects of cocaine administration on cytokine production were observed
      when female C57BL/6 mice were injected intraperitoneally with cocaine (40 mg/kg
      body weight for six weeks). Secretion of IL-2 by splenocytes was significantly
      enhanced by cocaine administration, whereas IFN-gamma was not affected. Secretion
      of IL-4 and IL-10 by splenocytes was significantly inhibited by cocaine
      administration, while secretion of IL-5 by splenocytes was significantly
      enhanced. Secretion of IL-6 and TNF-alpha by splenocytes was significantly
      enhanced by cocaine administration. Secretion of IL-6 by peritoneal macrophages
      was also significantly enhanced by the cocaine, while production of IL-1 alpha
      was not affected. However, release of TNF-alpha by peritoneal macrophages was
      significantly reduced by the cocaine administration. Therefore use of cocaine may
      alter the balance of cytokine production, and thereby adversely affects immune
      response and host defense.

PMID- 8295488
TI  - Effect of chronic IL-1 beta infusion on glucose homeostasis and pancreatic
      insulin secretion.
AB  - The present studies examined the effects of chronic interleukin-1 (IL-1 beta)
      infusion on glucose homeostasis and insulin secretion in male Sprague Dawley
      rats. IL-1 beta (4 micrograms per day) or saline was infused over a six day
      period using mini-osmotic pumps, surgically inserted under light ether
      anesthesia. Saline-infused rats were fed the amount of food consumed by their
      respective pair in the IL-1 beta group on the previous day. IL-1 beta infusion
      resulted in decreased food intake and significant body weight loss as well as
      increased liver and kidney weights. IL-1 beta infusion resulted in fasting
      hypoglycemia as well as elevated blood glucose levels in response to an oral
      glucose load compared to controls. Glucose-induced insulin secretion from the
      isolated perfused pancreas was significantly lower in IL-1 beta treated rats
      compared to controls. These data demonstrate that chronic IL-1 beta
      administration alters glucose homeostasis and impairs glucose-induced insulin
      secretion.

PMID- 8295489
TI  - Plasma endothelin levels in chronic ethanol fed rats: relationship to pathologic
      liver injury.
AB  - We used the intragastric feeding rat model for alcohol liver disease to
      investigate the relationship between endothelin and pathologic liver injury. Rats
      were fed the following diets for periods of 1, 2 and 4 weeks: corn oil plus
      ethanol (CE), corn oil plus dextrose (CD) and saturated fat plus ethanol (SE).
      Plasma endothelin levels were significantly higher in the CE group compared to
      the other groups at all time periods studied. The CE animals, also, developed
      pathologic liver injury which is in contrast to the SE and CD animals which
      showed no pathologic changes. We propose that endothelin, because of its powerful
      vasoconstrictive effects, leads to a reduction in hepatic blood flow which is
      important in the pathogenesis of alcoholic liver disease.

PMID- 8295490
TI  - A new method of purification and sensitive bioassay of platelet-activating factor
      (PAF) in human whole blood.
AB  - There is no satisfactory assay procedure of PAF in human whole blood in terms of
      sensitivity, reproducibility and simplicity. This is due to coexisting lipids
      from plasma and cellular membranes which inhibit measurement of PAF in various
      assay procedures, including bioassay. In the present study, an attempt was made
      to eliminate these interfering lipid inhibitors from blood samples. Lipids in
      human whole blood were extracted according to the method of Bligh & Dyer and the
      organic layer was dried under a stream of nitrogen. Then, the dried organic layer
      was dissolved in diethyl-ether and the solution was kept at -20 degrees C which
      was then centrifuged. The resulting supernatant was then applied to an anion
      exchange column and the PAF fraction was obtained by step-wise gradient elution.
      The fraction was further purified by normal phase HPLC. Then PAF in the final
      sample was determined by sensitive bioassay using rabbit platelets containing
      fibrinogen and epinephrine. The recovery rate of PAF throughout this procedure
      was constant and satisfactory (37.4 +/- 9.7%), which was confirmed using [3H]
      PAF. The lower limit of the present assay was estimated to be 5pg in 1 ml of
      blood and it was sensitive enough to detect PAF in blood samples from healthy
      volunteers and patients with sepsis or liver cirrhosis. Furthermore, attempts
      were made to compare the sensitivity and the recovery of our method with these of
      a commercially available radioimmunoassay (RIA) kit for PAF. However, it was not
      possible to detect any amount of authentic PAF added to whole blood.

PMID- 8295491
TI  - 3-O-methylglucose as probe of cytoplasmic volumes.
AB  - The intracellular volume of distribution (V) of 3-O-methylglucose (3OM), as
      calculated from mean artery-to-vein transit times (t)in the rabbit kidney, has
      been proposed as measure of cytoplasmic volume in renal cortex. This hypothesis
      requires that the non-concentrative uptake of the sugar be flow-dependent rather
      than diffusion-limited, and that total cell H2O (VHOH) exceed V3OM by a volume
      presumably reflecting that of 3OM-impermeable organelles. Diffusion-dependence of
      the calculated V3OM could be excluded by the finding that lengthening of t does
      not alter 3OM uptake. Determination of VHOH in kidney is complicated by presence
      of the luminal fluid compartment. VHOH and V3OM were therefore compared in
      leucocytes freshly prepared from rat blood; V3OM was found to equal 40% of VHOH.
      There is no evidence to suggest concentrative 3OM uptake by these cells; 3OM
      impermeable organelles therefore occupy 60% of VHOH. These findings support the
      equation of V3OM with the cytoplasmic volume. As volume control is a basic
      function of intact cells, convenient determination of VHOH and V3OM on small
      numbers of readily available nucleated cells may prove useful in detecting early
      cytotoxic effects in vivo or in vitro.

PMID- 8295492
TI  - The hepatitis-associated bile duct lesion.

PMID- 8295493
TI  - Epidemiology of hepatitis D virus (delta) infection in Yugoslavia.
AB  - In 614 HBsAg-positive Yugoslavian patients, radioimmunoassay testing for anti
      delta showed the presence of this antibody in serum in 11.2%. Of the patients,
      213 belonged to a risk group (i.v. drug users, hemophiliacs, hemodialysed
      patients and patients with posttransfusion hepatitis); a significant number of
      these patients (63; 29.6%) were found to have anti-delta. A second group was
      composed of 401 HBsAg-positive patients from the general population (patients
      with acute hepatitis B, with fulminant hepatitis B and patients with chronic HBV
      infection); delta infection was found only in six (1.5%). Immunohistochemical
      methods failed to demonstrate the delta antigen in the livers of 73 patients with
      chronic HBV infection. Testing the liver of 36 patients with fulminant hepatitis
      B for delta antigen demonstrated this reactivity in only one (2.8%) liver sample.
      Delta antigen was also found in the liver of a female patient who underwent
      biopsy in 1972. The results of this study suggest the HDV is not endemic in
      Yugoslavia; however, it is frequently found in patients at risk of blood
      exposure, primarily i.v. drug users.

PMID- 8295494
TI  - Hypercalcemia and parathyroid hormone-related protein in hepatocellular
      carcinoma.
AB  - A two-site immunoradiometric assay (IRMA) of parathyroid hormone-related protein
      (PTHrP) was employed to react with circulating concentrations of PTHrP in 14
      patients with hepatocellular carcinoma (HCC) and hypercalcemia (> 10.6 mg/dl).
      Eleven of them had unresectable lesions and three received transcatheter arterial
      chemo-embolization (TACE) treatment. Patients had no evidence of bony metastases
      and only one had evidence of a parathyroid lesion (by bone scan and serum
      parathyroid hormone level, respectively). The urinary cAMP level was increased in
      all patients, but the serum 1,25-dihydroxyvitamin D and plasma cAMP levels
      varied. Twelve patients had elevated alpha-fetoprotein (AFP) (> 400 ng/ml) and
      two of them had mildly elevated AFP levels (11 and 147 ng/ml). Their PTHrP
      concentrations were elevated (7.1 to 33.2 pmol/l), compared with normal levels
      obtained in our laboratory (< 3.5 pmol/l). A significant decrease in plasma PTHrP
      (from 27.4 to 5.2 pmol/l), serum calcium concentrations (from 16.3 to 9.4 mg/dl)
      and AFP levels (from 64,787 to 3129 ng/ml) was observed on the day following TACE
      treatment. These results, by using an improved technique, extend the findings
      that hypercalcemia in patients with HCC is associated with increased renal
      reabsorption of calcium and increased bone resorption of PTHrP generated by HCC.

PMID- 8295495
TI  - Pregnancy in patients with primary biliary cirrhosis--a case for dissuasion? The
      Swedish Internal Medicine Liver Club.
AB  - The medical literature on pregnancy in primary biliary cirrhosis is restricted;
      it mostly dates from several decades ago and mostly reports a bad prognosis for
      the fetus as well as for the liver disease. We report experiences based on four
      pregnancies in three patients with primary biliary cirrhosis which are at
      variance with those reported earlier.

PMID- 8295496
TI  - Magnetization transfer contrast imaging of hepatic neoplasms.
AB  - A method of performing magnetization transfer contrast (MTC) using a pulse
      sequence based on a series of on-resonance binomial pulses preceding a
      conventional spin-echo sequence has been recently described. We investigated this
      technique in the evaluation of circumscribed hepatic neoplasms on a 0.5 T imager.
      Conventional spin-echo imaging was performed in 18 patients with hepatic
      neoplasms, 15 with primary or metastatic hepatic neoplasms, and 3 with cavernous
      hemangiomas. The T1-weighted sequence was repeated following MTC saturation in 7
      patients and the proton density sequence was repeated following MTC saturation in
      13 patients (both were used in two patients). The mean lesion-to-liver contrast
      for neoplasms worsened with T1-MTC (0.87 vs. 1.04), but improved slightly with
      proton density-MTC (1.10 vs. 1.22) when compared to the corresponding non-MTC
      spin-echo images. However, these differences were not statistically significant
      (p = .19 and p = .16, respectively). The limited data on cavernous hemangiomas
      does not suggest these have consistently different MTC imaging characteristics
      from other hepatic neoplasms. In conclusion, MTC imaging using a binomial
      saturation pulse did not offer significant improvement in contrast between
      hepatic neoplasms and normal liver. Refinements of the binomial pulse sequence
      will be necessary if a consistent improvement in lesion sensitivity is to be
      achieved. Evaluation of its role in increasing diagnostic specificity will
      require further investigation.

PMID- 8295497
TI  - Numerical analysis of the magnetic field for arbitrary magnetic susceptibility
      distributions in 3D.
AB  - This paper demonstrates a method to calculate the magnetic field distribution in
      and around a 3D object when it is magnetized by a strong homogeneous magnetic
      field. The numerical technique is based on the explicit finite difference method.
      The calculation method is validated against analytical solutions for a sphere. As
      an application cylinders with different ratios of lengths and diameter are
      studied.

PMID- 8295498
TI  - Metabolic alterations in implanted human tumors after combined radiation and
      hyperthermia therapy measured by in vivo 31P MRS.
AB  - The bioenergetics of human lung tumors grown subcutaneously in KSN nude mice,
      were studied in vivo using 31P NMR spectroscopy up to 27 days following
      radiotherapy and/or hyperthermia. Six tumors were treated with radiation (20 Gy,
      single fraction) and hyperthermia (44 degrees C, 10 min). There was a significant
      increase in the ratio of inorganic phosphate to beta-nucleoside triphosphate
      (Pi/beta-NTP) 24 h after radiation plus hyperthermia (p < .01), but a significant
      decrease 6 days after the treatment (p < .05) relative to untreated controls.
      Furthermore, the combined therapy produce significant acidosis at 24 h post
      therapy followed by significant alkalosis at 6 days compared to no treatment.
      This biphasic pattern was also significant in comparison with the pretreatment
      values of Pi/beta-NTP and pH. The combined therapy produced not only tumor
      decline at 24 h indicated by increased Pi/beta-NTP ratio and acidic pH shift, but
      also metabolic activation of tumor cells at 6 days indicated by decreased Pi/beta
      NTP ratio and alkalotic pH shift. The tumor blood flow estimated by hydrogen ion
      clearance curves were completely depleted at 24 h and fully recovered to
      pretreatment level at 6 days. Reasonable close negative correlation between the
      blood flow and Pi/beta-NTP ratio (r = -0.59, p < .01) indicated that the two
      contrasting physiological states were closely related to tumor perfusion status.
      The 31P spectra of tumors following the combined therapy were concluded to
      demonstrate additive physiological effects of hyperthermia and radiation.

PMID- 8295499
TI  - Spin-echo methods for the determination of 31P transverse relaxation times of the
      ATP NMR signals in vivo.
AB  - 31P magnetic resonance spectroscopy (MRS) examinations of the calf muscles of
      healthy volunteers were performed to determine T2 of the coupled ATP signals by
      use of the Hahn spin-echo and the frequency-selective spin-echo method.
      Additional measurements with the J-coupling refocused double echo are presented.
      The most reliable determination of T2 relaxation times is possible with the
      frequency-selective spin echo. The other methods yield substantially wrong
      results. Theoretical explanations are given how J-coupling and pulse-angle
      deviations affect the signals and therefore the T2 determinations. The
      calculations for a weakly coupled homonuclear AX spin system are shown because
      they demonstrate most of the relevant facts. In addition, some important results
      for a homonuclear AMX spin system, which the ATP is considered to be, are given.

PMID- 8295500
TI  - 23Na magnetic resonance imaging: distribution of brine in muscle.
AB  - Magnetic resonance imaging (MRI) has been used to characterize tissues in
      morphological studies. Here, 23Na NMR imaging was used to study the distribution
      in muscle of brine (5 M NaCl), injected before onset of rigor mortis. First, the
      distribution of brine was monitored in excised muscle from rabbits for 6 hr
      following arterial brine injection. Immediately after injection, distribution was
      clearly heterogeneous. After 6 hr, a steady state was achieved but the observed
      brine distribution was not fully homogeneous. Second, the same was done for ham
      processed in various ways (tumbling, cooking). Tumbling increased the homogeneity
      of distribution in our experimental conditions but only cooking afforded full
      homogenization of brine in ham. Concentrations of NMR-visible sodium in the
      muscles were appreciably lower than the expected values calculated from the
      volume of injected brine. The invisible sodium presumably has T2 values which are
      too short compared with the echo time in our conventional spectrometer.

PMID- 8295501
TI  - Hippocampal formations imaging with axial sections parallel to their longitudinal
      axis.
AB  - The complex shape of hippocampal formation (HF) and its obliquity make its
      morphological analysis difficult using brain imaging techniques. Adapted planes
      of section are required. The hippocampal axial plane (HAP) parallel to the
      hippocampus long axis is able to provide a complete and comprehensive view of the
      structure. HF has a rostrocaudal extent and is divided into three parts, head,
      body, and tail. Histological sections in the HAP display very well the pattern of
      the cell layers, with their transversal folding at the head and the tail. At more
      ventral levels, HF sections consist of parts of the CA1 field and the subicular
      complex. These are completely embedded in the temporal lobe and separated from
      its medial surface by the white matter and the cortical plate of the
      parahippocampal gyrus. More dorsal sections allow the study of the amygdala,
      uncus and fimbria. Functional images of HF can be accurately defined by combining
      magnetic resonance imaging (MRI), positron emission tomography (PET), or single
      photon emission computed tomography (SPECT) in this plane. According to the small
      dorsal-ventral dimension of the structures, a few slices can cover the whole HF
      and precise regions of interest may be outlined.

PMID- 8295502
TI  - Fast 19F-NMR imaging in vivo using FLASH-MRI.
AB  - The goal of this study was the development of a method that allows the
      acquisition of chemical shift selective 19F NMR images within a short measuring
      time. A train of small tip angle frequency selective pulses, each followed by a
      dephasing gradient of random strength, was used as a presaturation experiment for
      the suppression of the unwanted chemical shift components. Imaging was performed
      after presaturation using a SNAPSHOT-FLASH experiment. The acquisition time for a
      64 x 128 image including the presaturation experiment amounted to only 470 ms.
      The sequence was applied in a 4.7 Tesla magnet to perform a longitudinal
      pharmacological study on the clearance of perfluoroocytlbromide (PFOB) in the
      liver and spleen of rats.

PMID- 8295503
TI  - MRI findings of concurrent acute DVT and dissecting popliteal cyst.
AB  - A case of concurrent popliteal vein thrombosis and a dissecting popliteal cyst
      noted on the same MRI exam is described. Pseudothrombophlebitis is a well known
      entity in which a ruptured or dissecting popliteal cyst clinically mimics
      thrombophlebitis; the current case can be considered "pseudo-pseudo
      thrombophlebitis." This case demonstrates the importance of routine review of the
      venous structures of the posterior fossa for all MRI exams of the knee.

PMID- 8295504
TI  - CT and MR of pineal region tumors.
AB  - Magnetic Resonance (MR) imaging features of pineal region tumors were analyzed in
      14 oncologic cases. The tumors were classified as germ-cell tumors, glial tumors,
      pineal parenchymal tumors, meningiomas, and cysts. They demonstrated different MR
      signal characteristics on precontrast scans and nodular or ring type enhancement
      with occasional central lucencies, except for benign cysts, which have not shown
      enhancement. MR images were useful in defining the relationship of the tumor to
      the posterior third ventricle, sylvian aqueduct, vein of Galen, and tentorium.
      Although CT can demonstrate in more evident fashion displacement of the original
      pineal calcification as well as tumor calcifications, MR imaging demonstrates
      different signal characteristics in germinomas and pineoblastomas which can be a
      useful adjunct in the evaluation and differential diagnosis of these tumors.

PMID- 8295505
TI  - The pulmonary artery acceleration time determined with the MR-RACE-technique:
      comparison to pulmonary artery mean pressure in 12 patients.
AB  - The goal of our study was to evaluate a rapid noninvasive MR technique for
      quantification of the pulmonary artery acceleration time (PAT) and other
      parameters of pulmonary hemodynamics and to correlate with pulmonary artery mean
      pressure (mPAP). The PAT known as "time-to-peak" out of Doppler echocardiographic
      measurements normally shows significant inverse correlation with mPAP. With the
      MR-RACE-Technique (RACE: Real time ACquisition and Evaluation of motion) blood
      velocity measurements can be obtained with a total acquisition time of a few
      seconds. The application of this technique to the pulmonary artery has not been
      reported before. Out of the RACE velocity wave form PAT can be obtained with a
      temporal resolution of about 15 ms. To explore the relationship between PAT and
      mPAP, right heart catheterization and MR-RACE measurements were performed in 12
      patients with different pulmonary vascular abnormalities. Results of MR-RACE were
      compared with those of mPAP measured by right heart catheter and showed
      significant inverse correlation (r = -0.82, p = .0011, n = 12). The ability of MR
      RACE to enable measurements of blood flow with profiles may be important for
      characterizing pulmonary and cardiovascular abnormalities.

PMID- 8295506
TI  - Magnetic resonance relaxation time mapping in multiple sclerosis: normal
      appearing white matter and the "invisible" lesion load.
AB  - Prolonged T1 and/or T2 relaxation times (RT) in the normal appearing white matter
      (NAWM) of patients with multiple sclerosis (MS) have been attributed either to a
      diffuse abnormality, or to "small lesions" undetected by visual inspection of
      conventional MR images. In a comparison of brain slices from five MS patients and
      five healthy control subjects, we have confirmed that the average T1 and T2 RTs
      obtained from NAWM in patients with MS are significantly prolonged (p < .04).
      Quantitative pixel-by-pixel mapping shows that this overall prolongation is due
      to the averaging of RTs from two subfractions of NAWM. In all patients a
      proportion (average 54% for T1 and 63% for T2) of the total white matter pixel
      sample from each MR brain slice had RT values indistinguishable from those found
      in the white matter of matched healthy control subjects (i.e., "normal normal
      appearing white matter," NNAWM). Scattered throughout the NAWM were multiple
      small areas, often of only one or two pixels, with abnormal RT values. These
      lesions, which were revealed only by pixel-by-pixel mapping of RT, made up a
      significant proportion (average 47% for T1 or 57% for T2 estimates) of the total
      (visible plus "invisible") lesion load per slice, and of the NAWM (average 36%
      for T1, 27% for T2), with wide interpatient variability. Further studies of these
      minute lesions are required to determine their total volume in the brain, their
      precise nature, evolution and relevance to the functional deficit in MS.

PMID- 8295507
TI  - Comparison of T1 estimation techniques in cardiac MRI.
AB  - We have shown that the use of a simple combination of inversion recovery/spin
      echo (IR/SE) sequences provides undeniably superior precision in quantitative in
      vivo myocardium T1 estimation than the standard multiple spin-echo approach. On a
      group of 25 healthy subjects, the T1 dispersion was, respectively, 3.8% for the
      IR/SE combination and 19.6% for the best SE pair combination. Moreover, repeated
      measurements were carried out on seven of the volunteers in order to assess T1
      reproducibility. The mean intra-individual T1 precision was found to be 2.8% for
      the IR/SE pair and 20.0% for the best SE pair. The in vivo imaging work was
      supported and corroborated by a thorough treatment of the theoretical T1 errors.
      We also highlight the importance of quality control in quantitative MRI; a
      correction being required in the SE sequences to bring measured signal
      intensities into line with those predicted from simple theory.

PMID- 8295508
TI  - Contrast induced myocardial signal reduction: effect of lanthanide chelates on
      ultra high speed MR images.
AB  - The myocardial MR signal reduction associated with an intravenous bolus of Gd
      DTPA and Dy-DTPA was studied in a canine model. Imaging was performed with a high
      speed echo-planar type imaging system (Instascan, Advanced NMR Systems, Inc.).
      Gated spin-echo images were obtained with TE of 30 ms, which permits image
      acquisition in approximately 40 ms. The gated TR was dependent on the heart rate,
      with an average TR of 2.4 s. After 0.1 mmol/kg of contrast was injected, 70
      images were acquired, which showed in an 80-image data set a reduction in
      myocardial signal with a gradual return to normal. After dipyridamole infusion,
      the signal loss was significantly more pronounced, and earlier than in the
      control data set. There was no significant difference between Gd-DTPA and Dy-DTPA
      in these imaging studies despite the theoretical prediction of better Dy signal
      reduction, possibly due to physiological variability during the course of a study
      or between studies. The cause of enhanced contrast effect after dipyridamole
      infusion is discussed, as is the basis for dipyridamole enhancement, and the
      possible role of contrast enhanced MR imaging in the detection of cardiac
      disease.

PMID- 8295509
TI  - Spin labelled arabinogalactan as MRI contrast agent.
AB  - In this study, we report the synthesis and the evaluation as MRI contrast agent
      of arabinogalactan/pyrrolidinoxyl radicals (PCA) covalent adduct (SLAG:Spin
      Labelled ArabinoGalactan). Arabinogalactan was used as targeting device, as it is
      recognized by the asialoglycoprotein receptor specific to the hepatocytes. The
      higher relaxivity R1 in water of SLAG, compared with small hydrophilic nitroxyl
      radicals, was explained by the molecular dynamics study using EPR spectroscopy
      that showed some immobilization of the radical into the polysaccharide. A binding
      study on isolated hepatocytes revealed that SLAG still recognizes the
      asialoglycoprotein receptor. MR imaging was performed using spin-echo T1 weighted
      images on mice to compare the contrast effect obtained with SLAG and PCA after IV
      injection (1 mmol/kg free radical). The percent signal enhancement observed in
      the liver 5 min after IV injection was 40 +/- 3% and 13 +/- 5% for SLAG and PCA,
      respectively. The signal was also dramatically increased in the renal cortex.
      This latter effect as well as the prolonged duration of the contrast (+/- 3 h),
      indicates at least a partial nonselective biodistribution; the high concentration
      needed to obtain a contrast effect could account for the saturation of the
      asialoglycoprotein receptor and hence for the apparent nonselective
      biodistribution.

PMID- 8295510
TI  - Differentiation of hepatomas from nonhepatomatous masses: use of MnDPDP-enhanced
      MR images.
AB  - Manganese (II) N,N'-dipyridoxylethylenediamine-N,N' diacetate 5,5'-bis(phosphate)
      (MnDPDP) is a hepatobiliary agent that is incorporated into the hepatocyte. We
      retrospectively reviewed our experience with 39 focal liver lesions in 20
      patients studies with MnDPDP-enhanced hepatic magnetic resonance (MR) imaging to
      determine whether hepatocellular carcinoma (HCC) could be differentiated from
      tumors of nonhepatocyte origin (metastases, cavernous hemangiomas, etc.) For all
      cases, liver parenchyma enhanced significantly following MnDPDP administration.
      All HCCs (6) showed significant tumor enhancement resulting in decreased tumor
      conspicuity compared to precontrast images [average 37% decrease in tumor-liver
      contrast to noise ratio (C/N)]. In contradistinction, other focal liver lesions
      showed little or no tumor enhancement resulting in increased lesion conspicuity
      (average 100% increase in tumor-liver C/N ratio). Our preliminary data suggest
      that MnDPDP-enhanced MR images may enable differentiation of HCC from other focal
      liver masses of nonhepatocyte origin.

PMID- 8295511
TI  - Measurement of capillary permeability from the Gd enhancement curve: a comparison
      of bolus and constant infusion injection methods.
AB  - Dynamic imaging of Gd-DTPA uptake has been used by several groups to characterise
      the permeability of blood-brain barrier and blood-retina barrier lesions, using
      both bolus and constant infusion rate injections. However, no consensus on which
      injection protocol is most efficient has been reached. To address this problem,
      we extend our Simplified Early Enhancement (SEE) theory, applicable to retinal
      lesions, to cover infusion injections, and demonstrate its application to
      published data. The two injection methods are compared using computer simulation.
      We find that, first, an infusion cannot produce a constant plasma concentration
      in an acceptable time (although a hybrid injection, consisting of a combined
      bolus and infusion, is able to do this). Second, at any given time after the
      start of injection, a bolus achieves a higher tissue concentration, and hence
      enhancement, than does the same dose given as an infusion. Conversely, a bolus
      achieves any given tissue concentration in a shorter time than the same dose
      given as an infusion. Consequently, a bolus uses a smaller dose to achieve a
      given enhancement at a particular time. Third, if renal function is reduced, the
      error in calculating the permeability from a particular value of enhancement is
      lower for the bolus than for the infusion. And last, the SEE method is more
      accurate for a bolus than for an infusion. We conclude that a bolus is always
      more efficient than an infusion, as well as being easier to administer, and
      should always be used in preference to an infusion.

PMID- 8295512
TI  - Functional 2D and 3D magnetic resonance imaging of motor cortex stimulation at
      high spatial resolution using standard 1.5 T imager.
AB  - This paper reports the effects of motor cortex stimulation of normal volunteers
      using conventional MR imaging techniques on standard 1.5 T clinical scanner.
      Improvement in signal-to-noise (S/N) ratio has been achieved by using a
      commercially available eye/ear surface coil with a loop of 8.5 cm in diameter.
      Magnet shimming with all first order coils was performed to the volunteer's head
      resulting in a magnetic field homogeneity of about 0.1-0.2 ppm. The imaging
      technique used was an optimized conventional 2D and 3D, first order flow
      rephased, gradient-echo sequence (FLASH) with fat-suppression and reduced
      bandwidth (16-28 Hz/pixel) and TR = 80-120 ms, TE = 60 ms, flip angle = 40
      degrees, matrix = 128 x 128, FOV = 150-250 mm, slice-thickness = 2-5 mm, NEX = 1,
      and a total single scan time for one image of about 12-16 s. In the 3D FLASH
      measurements, a slab of 32 mm thickness with 16 partitions was evaluated. The
      motor cortex stimulation was achieved by touching each finger to thumb in a
      sequential, self-paced, and repetitive manner. During stimulation, an increase in
      signal of order 10-20% was detected in the motor and sensory cortex due to
      reduced partial volume effects and optimized S/N for the measurements at small
      voxel size. 3D FLASH imaging at high spatial resolution shows good anatomical
      correlation of signal increase with gray matter of the motor and sensory cortex.
      The reported data demonstrate the technical feasibility of functional 2D and 3D
      MR imaging at high spatial resolution using optimized conventional sequences and
      equipment.

PMID- 8295513
TI  - Resonant trapezoidal gradient generation for use in echo-planar imaging.
AB  - Two passive filter circuit designs are compared which enable series resonant
      trapezoidal drive of the modulated read gradients used in both echo-planar and
      echo-volumar imaging. Using simple circuit simulation software, details of the
      expected power requirements and performance have been evaluated for peak
      operating currents of up to 1000 A. The circuits evaluated were of a 7th order
      design incorporating a 110 microH gradient coil operating at fundamental
      frequencies between 800 Hz and 2000 Hz. Results indicate that the simpler circuit
      design is not necessarily the most efficient. In addition, by suitable
      modification of the input waveform algorithm, it can be shown that the shape of
      the resonant gradient waveform may be varied entirely under software control from
      triangular to trapezoidal, the minimum ramptime being specified by the highest
      harmonic accommodated in the circuit. The energy storage, non-dissipative nature
      of the circuit design also means that the gradient ramptime is effectively
      independent of amplifier power capabilities, making a fast rise trapezoidal
      waveform as easy to implement as either triangular or sinusoidal waveforms. Using
      the approach outlined above, trapezoidal gradient modulation at peak current
      amplitudes in excess of 320 A and risetimes less than 60 microseconds have been
      easily produced in this laboratory for use in echo-planar imaging and for
      investigations into ways of optimising gradient performance before the onset of
      peripheral nerve stimulation.

PMID- 8295514
TI  - User-friendly forms for mother-baby nursing.

PMID- 8295515
TI  - Folic acid: consider the evidence.

PMID- 8295516
TI  - What pediatric home care offers the nurse.
AB  - Pammy had never been home in her 16 months of life. She'd never been in a car
      seat, seen her sister go off to school, or sat outside in her stroller. Today was
      the first day of a new life. While her Dad finished putting the crib together and
      the respiratory therapist arrived with the missing ventilator connector, her
      mother and her nurse Judy were accompanying her in the ambulance home. Soon her
      tube-feeding bag was hanging on a hook next to the "Welcome Home, Pammy" sign
      that a neighbor had made on his computer, and her four-year-old brother was
      building a runway under the nurse's feet. The back-up ventilator filled a quarter
      of the small living room, and the tubing, suction catheters, vent parts, formula,
      and water bottles filled the closet in Pammy's room--large enough because Mom and
      Dad had moved out of the master bedroom. Judy had helped Pam's mother set up the
      room a week ago and already had a sense of her concerns, the four-year-old's
      busyness, and the irregular schedule that the father worked. This would be an
      enjoyable, but challenging experience.

PMID- 8295517
TI  - Ambulatory care: challenges in patient teaching.

PMID- 8295519
TI  - Power analysis: Part I.

PMID- 8295518
TI  - Law versus ethics.

PMID- 8295521
TI  - A new standard of care for pediatric pain management.

PMID- 8295520
TI  - Fetal movement counting: which method?

PMID- 8295522
TI  - Iron overload? In sickle cell disease?

PMID- 8295523
TI  - Lithium and pregnancy.

PMID- 8295524
TI  - [Course and treatment of infantile asthma in our milieu].
AB  - We studied the clinical evolution and therapeutic approach of 50 children who
      were treated at the Emergency Room for an asthmatic crisis. We observed a high
      frequency of early onset of asthma before one year of age (n:16), constant
      symptoms between the crisis (n:34) and previous admissions before the present
      crisis (n:34) and previous admissions before the present crisis (n:16). Most
      cases did not have a family doctor. In 16 cases, the present crisis had four or
      more days of duration. We observed a frequent administration of suboptimal doses
      of bronchodilator and antiinflammatory drugs. These results show a non
      satisfactory treatment of infantile asthma.

PMID- 8295525
TI  - Corticotropin-releasing (CRH) activity of thymic peptides on CRH-insensitive
      corticotropic tumor cells.
AB  - A number of thymic preparations are known to stimulate corticotropin (ACTH)
      release from pituitary cells but it remains unclear whether this effect is
      mediated by the corticotropin-releasing hormone (CRH) receptor-associated
      pathway. We report here that thymosin fraction five (TF5), peptide MB-35 and
      possibly calf thymus histones can stimulate the release of ACTH from a CRH
      insensitive variant of the mouse corticotropic cell line AtT20. The effective
      concentration range at which TF5 and MB-35 displayed their ACTH-releasing
      activity in a dose-dependent manner was 100 to 2,000 micrograms/ml and 10 to 100
      ng/ml, respectively, whereas neither preparation induced a significant depletion
      of intracellular ACTH stores. Our data suggest that thymosin peptides can
      stimulate ACTH release from corticotrophs by a CRH receptor-independent
      mechanism.

PMID- 8295526
TI  - [Anticytoplasm antibodies of polymorphonuclear neutrophils in Wegener's
      granulomatosis, other autoimmune diseases, and in patients undergoing
      hemodialysis].
AB  - Systemic vasculitis are an heterogeneous group of diseases characterized by
      inflammatory infiltration and necrosis of blood vessel walls. Antineutrophil
      cytoplasmic antibodies (ANCA) with different immunofluorescent patterns (C or P)
      have been described as serological markers of some of these diseases and some
      types of glomerulonephritis. The presence of ANCA by immunofluorescence on normal
      fixed polymorphonuclear neutrophils was investigated in 182 patients. Results are
      depicted in Table 1. ANCA was present in 16/17 (94%) patients with Wegener
      Granulomatosis (W.G.) (ACR criteria) (p < 0.001). In 14 out of the 16 (82%), the
      pattern was ANCA-C (associated in 10 with ANCA-P) and only ANCA-P was observed in
      the remaining two. The presence of ANCA was associated with active disease: 15/16
      samples of active patients and 3/9 of inactive patients were ANCA positive (p <
      0.01). Among the other groups, ANCA-C was detected in only one patient with
      isolated subglottal stenosis. The specificity of ANCA-C for W.G. was 99%. ANCA-P
      was also detected in 3/49 (6%) patients with connective tissue disorders and in
      3/63 (5%) patients in chronic hemodialysis with exclusive or predominant renal
      disease of unknown etiology. Three additional ANCA positive patients with known
      diagnosis (2 W.G. and 1 Systemic Lupus Erythematosus) were also in hemodialysis
      in the same unit. Thus, an ANCA related mechanism may be involved in the
      pathogenesis of approximately 10% of cases undergoing this procedure. None of 45
      sera submitted for the detection of antinuclear antibodies were ANCA positive.
      Detection of ANCA (especially C pattern) may be of help in the diagnosis of W.G.
      and in monitoring clinical activity of the disease.

PMID- 8295527
TI  - [Serum testosterone: a possible marker for colorectal cancer].
AB  - A reduction of circulating testosterone has been reported in lung, stomach and
      pancreatic carcinoma. In order to evaluate the concentration of this hormone in
      patients with colorectal cancer, we studied 58 men with histologically confirmed
      disease. Seric testosterone, estradiol and carcinoembryogenic antigen were
      simultaneously measured in 24 patients under pre-surgical evaluation (group I)
      and in 34 patients after surgical resection (group II). The results were compared
      with a control group carrying benign gastrointestinal pathologies. According to
      the Kruskal-Wallis test, the testosterone level in cancer groups was
      significantly lower than in the control group (p < 0.0001). We have also observed
      a statistical significance between subgroups I and II compared to the control
      group (p < 0.001), while no conspicuous differences were perceived in estradiol
      concentrations between benign and cancer groups. Decreased serum levels of
      testosterone were found in 69% of patients with colon or rectal carcinoma and
      56.9% of them had raised levels of carcinoembryonic antigen. The combined
      determination of both biomarkers increase to 86.2% the sensitivity of tumor
      screening compared with a single detection. Our results suggest that the
      combination of testosterone and carcinoembryonic antigen enhances the efficiency
      of tumor screening. We conclude that the evaluation of circulating testosterone
      could be a new and more sensitive assay for diagnosis and follow-up of colorectal
      carcinoma in males, specially in patients with normal levels of carcinoembryonic
      antigen.

PMID- 8295528
TI  - [Evaluation of alternative hemoculture tests for the diagnosis of early neonatal
      sepsis].
AB  - In order to evaluate the diagnostic usefulness of coadjuvant tests such as
      external auditory canal swab culture and cultures from nasopharyngeal and gastric
      aspirates, and to determine the incidence and etiology of early neonatal sepsis
      (ENS) at our Unit, 90 newborn cases whose mothers experienced premature rupture
      of the membranes (PRM) were studied prospectively. Although a firm diagnosis
      requires positive blood cultures, the difficulty in recovering microorganisms and
      the trauma induced by sample collection in the baby justify the search for
      alternative diagnostic tests. Out of 2293 childbirths during 1991, 90 mothers
      (4%) had PRM more than 24 hours pre-partum, while 6.9/1000 (16/2293) developed
      ENS. In newborns from PMR mothers, ENS percentage was 3.3%, but increased to 5.5%
      in association with chorionamnionitis and reached 8.8% in premature cases. Among
      etiological ENS agents, Gram-positive microorganisms predominated (Table 1),
      particularly Staphylococcus aureus. Despite the finding that none of the
      coadjuvant assays (Table 2) had sufficient sensitivity or positive predictive
      value to identify all septic cases, they may prove useful to pinpoint newborns at
      high risk due to amniotic fluid exposure to infection or to chorioamnionitis.

PMID- 8295529
TI  - Functional changes of the sciatic nerve in mice chronically infected with
      Trypanosoma cruzi.
AB  - Early histological studies carried out in the sciatic nerve of mice chronically
      infected with Trypanosoma cruzi showed demyelination and scanty axonal
      degeneration. The experiments reported in this paper were designed to assess the
      functional state of the sciatic nerve and of some of the muscles it supplies. For
      these purposes 14 mice were infected with trypomastigotes (clon K-98, CA-I
      strain) 12 months before the investigation. Results were compared with 13 normal
      mice matched by age and weight. Hamstring muscles were studied
      electromyographically by means of a fine coaxial needle electrode and the sciatic
      nerve action potential characteristics were recorded with surface electrodes. All
      the experiments were carried out in vivo. In the infected mice the electromyogram
      showed that some motor unit potentials has enlarged amplitude and duration and
      increased number of phases, suggesting that the size of their territories had
      been enlarged, probably through axonal collateral sproutings and reinnervation of
      muscle fibers previously relinquished by their original innervation. The sciatic
      nerve action potential of the infected animals showed diminished amplitude and
      prolonged latency. These features signal reduced number of functional axons
      within the nerve and demyelination of the remaining conducting fibers. These
      findings are in line with the histological evidences of the involvement of the
      peripheral nervous system in Chagas disease and give additional information about
      the functional state of the peripheral nerves in the experimental model.

PMID- 8295530
TI  - [Influence of sodium butyrate intake on murine colonic carcinogenesis].
AB  - The role of short chain fatty acids (SCFA) in murine colonic carcinogenesis (MCC)
      has not yet been clarified. In rats, Freeman et al have reported an increased
      number of colonic tumors induced with dimethylhydrazine (DMH) and sodium butyrate
      in drinking water. On the other hand, Deschner et al showed that tributyrin
      intake did not increase MCC induced with azoxymethane. Both of them have reported
      high levels of fecal butyric acid with sodium butyrate and tributyrin intake.
      Although salt intake has been positively associated with colorectal cancer some
      authors do not support this association. We have evaluated the influence of right
      hemicolectomy (RH) (right colon as main source of SCFA) and the intake of 2%-pH 7
      sodium butyrate (S.BUT) and 4 g/l sodium chloride (S.CHL) in drinking water, in
      MCC. Forty eight male Wistar rats weighing 150 g were divided into 4 groups: RH,
      S.BUT, S.CHL, control (C). Half of the animals received weekly DMH 20 mg/kg
      subcutaneously for 12 weeks. Necropsy was performed after 6 months. We have
      determined fecal SCFA content by gas chromatography. Neoplasm was present in 70%
      of rats treated with DMH. The number of animals with tumors was: RH 4/6, S.BUT
      4/6, S.CHL 3/5, C 6/6. Tumor frequency was: RH 1.17 +/- 0.48, S.BUT 1.50 +/-
      0.76, S.CHL 1.20 +/- 0.49, C 1.50 +/- 0.22. S.BUT group, treated with DMH,
      presented a lower butyric acid concentration (p < 0.05) in comparison with other
      groups. We have no explanation for this finding; gastric absorption of sodium
      butyrate may be an important factor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295531
TI  - [Pregnancy with spermatozoa from the head of the epididymis in spermatic duct
      agenesis].
AB  - From a male affected of agenesis of corpus and cauda epididymis and vas deferens,
      sperms were surgically obtained aspirating epididymal content with the help of a
      surgical microscope. Motile sperms were separated after discontinuous Percoll
      gradient centrifugation and used to inseminate in vitro the spouse's oocytes 8
      hrs. after aspiration according to the current techniques. Twenty hours later,
      oocytes were checked for fertilization and transferred to fresh culture medium.
      From 13 preovulatory oocytes only one was fertilized and transferred to the
      Fallopian tube at the 6 cells stage. Fourteen days after embryo transfer, serum
      HCG concentration was 320 mU/ml and on day 29th a 5mm fetal sac showing heart
      beats was detected by transvaginal sonography. After an uneventful 38 weeks
      gestation a normal baby girl weighing 2,800 g was delivered.

PMID- 8295532
TI  - [Dyspnea, hypoxemia, and arrhythmia in a patient with cardiac pacemaker].

PMID- 8295534
TI  - [Hematopoiesis regulation].
AB  - Positive and negative signals are crucial in the regulation of the hematopoietic
      system. In the last 30 years, more than 20 molecules (glycoproteins) with
      biological activity upon the hematopoietic progenitor cells and even on the
      mature blood cells have been purified. The best known of these biomolecules are
      the hematopoietic growth factors (colony stimulating factors and interleukins),
      which are able to stimulate bone marrow cells to give mature progeny. At present,
      not only the sequence of the majority of these glycoproteins and their codifying
      genes has been determined, but also their target cells and cellular receptors.
      Research studies of the interaction between the hematopoietic progenitor cells
      and their stimulating and inhibiting factors are very helpful in the development
      of clinical trials and have become important tools to explore the origin of a
      great number of hematological diseases. However, the mechanisms underlying
      growth/inhibitory factor production and progenitor cell proliferation remain
      poorly understood.

PMID- 8295533
TI  - [Molecular markers to predict the prognosis of breast cancer].
AB  - The incidence of breast cancer is 25-30% of all malignant female tumors and
      represents the highest rate of mortality. To define those breast cancer patients
      at higher risk several prognostic factors are routinally evaluated in the primary
      tumor. Among them, the presence and degree of tumor involvement in axillary lymph
      node is one of the most powerful prognostic indicator. However, around 30% of
      node negative patients (good prognosis group) have recurrences and die within the
      next 10 years from diagnosis. Therefore, there is a need for markers to better
      discriminate biologic differences in the primary tumors. The techniques of
      molecular biology are shedding new insight into the subcellular pathology of
      malignancy. The crucial events of carcinogenesis, tumor progression, and
      metastatic spread are coming into focus at a molecular level. In some tumors,
      these advances in the laboratory are beginning to have applications at the
      bedside. Recently, abnormalities in the copy number and expression of several
      genes have been correlated with prognosis of individual patients with selected
      types of cancer. Molecular biology laboratories can provide useful predictive
      information that can be used to influence decision on the selection of treatment
      and to estimate a better risk stratification. Among these new markers are:
      oncongene amplification and/or over-expression, growth factors, cellular
      proliferation rate and ploidy, estrogens induced proteins, expression of
      metastasis related molecules, drug resistance associated proteins, etc. In this
      article we attempt to present a brief evaluation of a new technology that
      promises to add greater precision in evaluating molecular tumor markers and we
      mention some of its clinical applications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295535
TI  - [Percutaneous drainage of abscesses: an application of intervention radiology].

PMID- 8295537
TI  - [From the double helix to gene therapy].

PMID- 8295536
TI  - [Diagnostic applications of polymerase chain reaction].

PMID- 8295538
TI  - [The effect of L-thyroxine amino acid on human melanoma cell lines].

PMID- 8295539
TI  - [Gastric cancer. Clinico-pathological characteristics and expression of c-erB-2
      oncogene in 122 cases].
AB  - A series of 119 patients with 122 gastric carcinomas treated by gastrectomy, with
      a follow up of more than 5 years is presented. There were 80 (67.2%) men and 39
      (32.8%) women with a mean age of 66.4 years. In 101 (84.9%) the diagnosis of
      cancer was endoscopic. Pain was the most frequent symptom (55.5%). Seventy two
      (59%) were localized in the antrum; 26 (21%) were cardial, and 24 (19.7%) were in
      the body. In 43.4% the size was smaller than 5 cm and in 56.6% it measured 5 cm
      or more. Eighty nine (73%) were of the intestinal type, 15 (12.3%) were diffuse
      and 18 (14.8%) were mixed. Eighty (65.6%) were low histological grade and 42
      (34.4%) were high grade. Ten (9.2%) were early carcinomas and 112 (91.8%)
      advanced carcinomas. An amplification of the c-erbB-2 oncogene was associated
      with tumors that were smaller than 5 cm (p = 0.05) and with histological low
      grade (p = 0.005). A five years survival correlated with tumors smaller than 5 cm
      (p = 0.02), with parietal infiltration not surpassing the muscular layer (p =
      0.001), and without lymph node metastases (p = 0.001). There was no association
      between survival and amplification of c-erbB-2 oncogene.

PMID- 8295540
TI  - Decision-support systems as safety-critical components: towards a safety culture
      for medical informatics.

PMID- 8295541
TI  - Medical database security policies.
AB  - Database security plays an important role in the overall security of medical
      information systems. Security does not only involve fundamental ethical
      principles such as privacy and confidentiality, but is also an essential
      prerequisite for effective medical care. The general framework and the
      requirements for medical database security are presented. The three prominent
      proposals for medical database security are discussed in some detail, together
      with specific proposals for medical database security. A number of parameters for
      a secure medical database development are presented and discussed, and guidelines
      are given for the development of secure medical database systems.

PMID- 8295542
TI  - Distinguishing individual linkages of personal records from family linkages.
AB  - Errors occur in the automated linkage of medical and other records into personal
      histories, when household and family identifiers get wrongly treated in the same
      way as the strictly personal identifiers. This is because overwhelming evidence
      that two records refer to the same household or family, does not mean they
      necessarily represent the same person. Current practice in probabilistic record
      linkage fails to make this distinction, and combines indiscriminately the
      calculated odds from the mix of identifiers pertaining to all three sorts of
      entity. A tactic is described that avoids the resulting problem of mistaken
      personal identity. It does so by first converting composite odds from comparisons
      of household and family particulars, to a magnitude that contributes correctly to
      the overall evidence in favour of a strictly personal linkage.

PMID- 8295543
TI  - User evaluation of an integrated medical workstation for clinical data analysis.
AB  - Results are presented of the user evaluation of an integrated medical workstation
      for support of clinical research. Twenty-seven users were recruited from medical
      and scientific staff of the University Hospital Dijkzigt, the Faculty of Medicine
      of the Erasmus University Rotterdam, and from other Dutch medical institutions;
      and all were given a written, self-contained tutorial. Subsequently, an
      experiment was done in which six clinical data analysis problems had to be solved
      and an evaluation form was filled out. The aim of this user evaluation was to
      obtain insight in the benefits of integration for support of clinical data
      analysis for clinicians and biomedical researchers. The problems were divided
      into two sets, with gradually more complex problems. In the first set users were
      guided in a stepwise fashion to solve the problems. In the second set each
      stepwise problem had an open counterpart. During the evaluation, the workstation
      continuously recorded the user's actions. From these results significant
      differences became apparent between clinicians and non-clinicians for the
      correctness (means 54% and 81%, respectively, p = 0.04), completeness (means 64%
      and 88%, respectively, p = 0.01), and number of problems solved (means 67% and
      90%, respectively, p = 0.02). These differences were absent for the stepwise
      problems. Physicians tend to skip more problems than biomedical researchers. No
      statistically significant differences were found between users with and without
      clinical data analysis experience, for correctness (means 74% and 72%,
      respectively, p = 0.95), and completeness (means 82% and 79%, respectively, p =
      0.40).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295544
TI  - A modular knowledge base for the follow-up of clinical protocols.
AB  - From the knowledge engineering point of view, the observation of patients
      subjected to clinical protocols of therapy constitutes a domain characterized by
      the existence of strongly structured knowledge. We have approached the problem
      from the perspective of a homogeneous and modular knowledge representation
      theory, based on the concept of Generalized Magnitude. This concept arises from
      identifying and collecting all possible facts of a domain established a priori,
      and being inspired by the concept of physical magnitudes. The Generalized
      Magnitudes scheme includes temporal extensions necessary to solve a medical
      problem for which exists a therapy and a follow-up plan with temporal
      specifications, and also facilitates the creation of advisory expert systems.

PMID- 8295545
TI  - Risk adjustment in outcome assessment: the Charlson comorbidity index.
AB  - To measure the burden of comorbid diseases using the MED-ECHO database (Quebec),
      the so-called Charlson index was adapted to International Classification of
      Disease (ICD-9) codes. The resulting comorbidity index was applied to the study
      of inpatient death in a group of 62,456 patients having one of the following
      conditions: ischemic heart disease, congestive heart failure, stroke, or
      bacterial pneumonia. Multiple logistic regression was used to relate inpatient
      death to its predictors, including gender, principal diagnosis, age, and the
      comorbidity index. Various transformations of the comorbidity score were
      performed, and their effect on predictive accuracy was assessed. The comorbidity
      index was constantly and strongly associated with death. When gender, age,
      comorbidity and the principal diagnoses were taken into account, the area under
      the receiver-operating curve was 0.83. Therefore, the Charlson Index is a useful
      approach to risk adjustment in outcomes research from administrative databases.

PMID- 8295546
TI  - Influence of "outliers" on the association between laboratory data and
      histopathological findings in liver biopsy.
AB  - Discriminant analysis techniques were used to predict the histopathological
      findings in liver biopsy specimens in asymptomatic patients with slightly to
      moderately raised routine liver tests. Moderate to severe fibrosis and/or
      inflammation were treated as indication for biopsy. Two methods were used to
      classify patients. One was the dichotomous discrimination between "biopsy
      necessary" or "biopsy not necessary" groups of patients. The other involved
      combining two discriminant functions trained separately for recognition of
      fibrosis or inflammation, and then combined to predict the biopsy necessity.
      Detection of outliers by standard techniques, directly available in the SPSS-X
      package, was performed before starting discrimination procedures. Both "sharp"
      assignment rules and continuous scoring rules were applied to the classification
      problem. The correct classification rate reached over 85% for the algorithms
      tested. In the majority of cases the classification was found to be "non
      doubtful". Elimination of outliers (especially by standardized residuals)
      improved the global correct classification rate, but only slightly improved
      assignment to the "biopsy necessary" group. Routine and complementary laboratory
      findings were found to be the most discriminating; answers to questionnaire and
      ultrasound examination were less important. Selection of the most diagnostic
      features based on "clean" data without outliers enabled us to find interesting
      medical associations, which were previously masked by extremely asymptomatic
      values outlying from the main body of the "biopsy necessary" group.

PMID- 8295547
TI  - Clinical decisions for psychiatric inpatients and their evaluation by a trained
      neural network.
AB  - Ninety-two consecutive treatment decisions regarding psychotic and depressed
      inpatients were evaluated by a trained neural network. Simultaneous evaluations
      according to the Brief Psychiatric Rating Scale (BPRS), the Hamilton scale, and
      the neural network were performed. A 15-point decrease in the BPRS for psychotic
      patients or a 10-point decrease in the Hamilton scale for depressed patients was
      the cut-off point for treatment success. The neural network performed similarly
      to the clinicians. The combined clinician-network success rate reached 79% and
      was significantly higher than that for each alone. Clinicians and neural network
      disagreed on 62% of decisions made for depressed patients and on 55% of decisions
      made for psychotic patients. The proportion of agreement was lower in both
      diagnostic groups than expected by chance. However, the high success of the
      combined clinician and neural network decisions and the high rate of mutual
      disagreement may imply that a combined decision is fruitful.

PMID- 8295548
TI  - The development and practical use of information systems in the pharmaceutical
      industry.
AB  - To provide information on the efficacy, safety, and quality of medicine promptly
      and accurately, we have developed two databases: a literature database with
      numerical data, and a Drug Information database. By an easy-to-use, company-wide
      information network system, over 1,000 medical representatives in more than 80
      offices throughout Japan can retrieve information. Information derived from the
      system is displayed on the terminal and the original documents are automatically
      output through a facsimile.

PMID- 8295549
TI  - Virtual reality in medicine.
AB  - Virtual reality (VR), as part of computer science, allows computer-based models
      of the real world to be generated, and provides humans with a means to interact
      with these models through new human-computer interfaces and, thus, to nearly
      realistically experience these models. This contribution explores the technical
      requirements for VR, describes technological advances and deficits, and analyzes
      the framework for future technological research and development. Although some
      non-medical applications are discussed, this contribution focuses primarily on
      medical applications of VR and outlines future prospects of medical VR
      applications. Finally, possible hazards arising from the use of VR are discussed.
      The authors recommend an interdisciplinary approach to technology assessment of
      VR.

PMID- 8295550
TI  - Revising a display of multidimensional laboratory measurements to improve
      accuracy of perception.
AB  - To display multidimensional laboratory measurements, Hoeke et al. (1991) proposed
      a technique that uses plotting axes radiating from a point, assigns each test to
      a separate axis, and links the test results with line segments. A special
      nonlinear scaling ensures that a patient whose results all fall in the normal
      range is represented by a regular polygon of middle size, and colored zones
      emphasize more serious departures from the normal range. Results of research in
      graphical perception, however, point to potential difficulties in clinical
      applications. Those results also suggest a revision of the display that should
      overcome the difficulties. The new version plots the test results on parallel
      horizontal lines and links the points for adjacent tests by line segments, while
      retaining the special scaling and the colored bands.

PMID- 8295551
TI  - On the use of graphics to represent laboratory measurements.

PMID- 8295552
TI  - The influence of haemin levels on growth and enzyme production by Porphyromonas
      gingivalis in continuous culture.
AB  - Porphyromonas gingivalis was grown in continuous culture in brain heart infusion
      medium with haemin (5 microgm 1(-1) to 10 mg 1(-1)). Growth was haemin-limited up
      to 400 microgm 1(-1), and steady-state growth could not be obtained in the
      absence of haemin. It was confirmed that protoporphyrin IX could replace the
      haemin requirement. The results indicate that P. gingivalis has more than one
      uptake system for haemin, one of which is high affinity. The effect of haemin on
      hydrolytic enzyme production revealed a complex picture. Trypsin-like protease
      activity peaked at 200 microgm 1(-1) with a substantial and highly significant
      reduction at high (2 and 10 mg 1(-1)) concentrations of haemin. Alkaline
      phosphatase also peaked around 100 to 400 microgm 1(-1) while N-acetyl-beta
      glucosaminidase was not greatly affected except that a greater proportion of
      enzyme was secreted into the medium at the lowest haemin concentration. In
      general, haemin-limitation enhanced export of the hydrolytic enzymes to the
      extracellular vesicle fraction. Protoporphyrin IX at 2 mg 1(-1) caused a highly
      significant reduction i the production of all three enzymes.

PMID- 8295553
TI  - Enzymatic differentiation and biochemical and serological characteristics of the
      clinical isolates of Streptococcus angiosus, S. intermedius and S. constellatus.
AB  - Of the 29 'Streptococcus milleri' strains tested, all thirteen Streptococcus
      intermedius (DNA homology group 2) strains but none of the thirteen Streptococcus
      anginosus (group 1) strains produced beta-N-acetylglucosaminidase, beta-N
      acetylgalactosaminidase, alpha-N-acetylneuraminidase, beta-galactosidase, alpha
      glucosidase, and hyaluronidase. The three Streptococcus constellatus (group 3)
      strains produced only the latter two. Glycosidase production divided 274 clinical
      isolates into 103 S. anginosus, 101 S. intermedius, and 70 S. constellatus
      strains. Generally, strains of S. anginosus and S. intermedius were non-beta
      haemolytic. API II and biotype Ia (lactose positive), but the former contained
      almost all API III strains and belonged to Lancefield group A/serotype a (A/a), 
      /b, C/c, -/d, -/e, F/f or G/k, and the latter included most of biotype IId
      (lactose negative) and serovar -/g, -/h, -/i or -/j. S constellatus strains were
      beta-, alpha- or gamma-haemolytic, of API I or II but mostly biotype Ib (lactose
      negative), and of F/- or -/b. S. intermedius was a major member of the oral
      isolates. Non-oral isolates were virtually all S. anginosus (mainly urogenital
      isolates) or S. constellatus (the other systemic isolates).

PMID- 8295554
TI  - Binding of Fc fragments of IgG from human and seven animal species to Mycoplasma
      salivarium cells.
AB  - Mycoplasma salivarium cells were demonstrated to bind human IgG Fc fragments. The
      binding capacity was 78.8% enhanced by incubation of the cell suspension in PBS
      with 0.25% trypsin at 37 degrees C for 1 h, but tended to fall after incubation
      with higher concentrations of the enzyme, and was 95.5% lower after incubation of
      the suspension without trypsin. Fc fragments of IgG from rat, swine, sheep,
      rabbit, goat, cow and mouse also bound to the organism cells with increasing
      affinity in this order. The affinity of human IgG Fc fragments was almost
      comparable with those of sheep and rabbit. Antigen specific IgG from goat
      (specific for gamma-chain of human IgG, and mu-chain of human IgM) and rabbit
      (specific for whole molecules of goat IgG) bound to the cells. Binding of goat
      IgG Fc fragment was inhibited in the presence of antigen specific goat IgG
      (specific for gamma-chain of human IgG). These results suggest that M. salivarium
      cells bind IgG from a variety of animal species via the Fc fragment.

PMID- 8295555
TI  - POs hit the ground running.

PMID- 8295556
TI  - MSMS conducts PO/PHO survey. Respondents cite enhanced autonomy, better patient
      care as the motivating factors for joining POs/PHOs.

PMID- 8295557
TI  - Enterprise liability. A dangerous quick fix.

PMID- 8295558
TI  - MSMS provides a strong voice for medicine. Take a moment to review the program.

PMID- 8295559
TI  - Impaired physicians: new law stresses "treatment rather than punishment".

PMID- 8295561
TI  - Graduate medical education. Let's keep up!

PMID- 8295560
TI  - Judicial commission & risk management. Commission routinely receives questions,
      complaints about access to medical records.

PMID- 8295562
TI  - The entry and intracellular multiplication of Francisella tularensis in cultured
      cells: its correlation with virulence in experimental mice.
AB  - Five acriflavine agglutination test-positive (acf+) colonies and five negative
      (acf-) colonies were isolated from each of the four strains (Ebina, CMB2, N9, and
      Schu) of Francisella tularensis, and the correlation between the virulence in
      experimental mice and the entry and intracellular multiplication in cultured
      mouse fibroblast cells (L-929 cells) was examined. All of the acf- colonies
      derived from the Ebina and CMB2 strains were highly virulent in mice, readily
      entering and growing well in the cells, while all of the acf- colonies from N9
      and Schu strains were of low virulence and neither entered nor grew in the cells
      effectively. On the other hand, regardless of their parent strains, the acf+
      colonies were low virulent and most of those colonies did neither enter nor grow
      in L-929 cells. In addition, two acf- colonies, one from the N9 and the other
      from the Schu strain, gained virulence through several passages in mice, and in
      parallel, their entry and multiplication also improved. However, two acf+
      colonies from the Ebina strain and one acf+ colony from the N9 strain showed a
      moderate degree of the entry and multiplication although they were all low
      virulent. The overall results indicate that the entry and multiplication in cells
      are important factors regulating the virulence of F. tularensis. The results also
      showed, however, that they were not sole factors to elucidate the virulence of
      the bacterium in mice.

PMID- 8295563
TI  - The structure of Mycoplasma pneumoniae as determined by the freeze-substitution
      technique.
AB  - The ultrastructure of Mycoplasma pneumoniae FH was examined by a mild fixation
      method, the freeze-substitution technique, for thin-section transmission electron
      microscopy and the following new findings were obtained. In the cytoplasm, no
      nuclear region could be clearly identified. The cytoplasm was filled with many
      ribosome-like particles, fine fibers and electron-dense particles. The electron
      dense particles appeared to be similar to the particles found in the nucleoid
      region of Pseudomonas aeruginosa and might therefore possibly be a kind of DNA
      binding protein. The cell surface was completely enveloped with a thin opaque
      layer. The presence of this surface layer prevented any direct contact of the
      cell surface with that of the two M. pneumoniae cells.

PMID- 8295564
TI  - Potent in vitro bactericidal activity of polymyxin B against methicillin
      resistant Staphylococcus aureus (MRSA).
AB  - Eradication of methicillin-resistant Staphylococcus aureus (MRSA) carried by
      inpatients or healthy hospital personnel by topical use of antibiotics is an
      important step for preventing outbreak of MRSA nosocomial infection. In the
      screening of the antibiotic best suited for this purpose, we have found that
      polymyxin B, a commonly used antibiotic for gram-negative infection, had an
      unexpected strong cytokilling activity towards MRSA clinical strains, which was
      more potent than that of vancomycin or gentamicin. The data suggested that
      polymyxin B could be an antibiotic of choice in the treatment of topical carriage
      of or infection caused by MRSA.

PMID- 8295565
TI  - Purification and characterization of a protein cryoprotective for Vibrio cholerae
      extracted from the prawn shell surface.
AB  - A substance cryoprotective for Vibrio cholerae on the prawn shell surface was
      purified by ammonium sulfate precipitation and gel filtration. It was a protein
      of 81 kDa and called cryoprotective protein (CPP). The cryoprotective activity of
      this protein for V. cholerae was sensitive to heat at 100 C and trypsin
      treatment. In the presence of Mg ion the protein can bind to the bacterial cell
      surface. V. cholerae can adhere to the shell surface of the prawn. The number of
      adhered bacteria was reduced by treating the shell with anti-CPP serum, heat or
      by trypsin. The presence of Mg ion promoted the adherence. These results suggest
      that the CPP could serve as an adherence site for V. cholerae on the shell
      surface.

PMID- 8295566
TI  - Antiviral activity of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil against
      thymidine kinase negative strains of varicella-zoster virus.
AB  - Mechanism of antiviral activity of 1-beta-D-arabinofuranosyl-E-5-(2
      bromovinyl)uracil (BV-araU) against the YSR strain of varicella-zoster virus
      (VZV), which is a mutant derived from the wild YS strain and is completely
      deficient in viral thymidine kinase (TK), was searched in comparison with
      antiviral activity of other thymidine analogues, guanosine analogue and
      thymidylate synthase (TS) inhibitor in human embryo lung fibroblast cells.
      Thymidine analogues, such as BV-araU,5-iododeoxyuridine (IUDR), 1-beta-D
      arabinofuranosylthymine (araT), and guanosine analogue, such as 9-(2
      hydroxyethoxymethyl)guanine (ACV), showed higher antiviral activity to the YS
      strain than to the YSR strain. Though, BV-araU also had the antiviral activity of
      a microgram level against the YSR strain. In contrast to these results, TS
      inhibitor, 5-fluorodeoxyuridine (FUDR), had higher antiviral activity to the YSR
      strain than to the YS strain. Highly synergistic antiviral activities of FUDR to
      the YS strain and the YSR strain were observed in combination with IUDR, araT, or
      ACV. However, weakly synergistic or additive inhibition to the YSR strain was
      shown in combination of BV-araU and FUDR, in spite of highly synergistic effect
      of this combination to the YS strain. The viral and cellular TS activity was
      partially inhibited by BV-araU monophosphate, but not by BV-araU. These results
      indicate that BV-araU is converted into BV-araU monophosphate by cellular TK, and
      the inhibition of TS activity by BV-araU monophosphate in the YSR strain-infected
      cells results in the suppression of viral replication.

PMID- 8295567
TI  - Influence of a small number of mature T cells in donor bone marrow inocula on
      reconstitution of lymphoid tissues and negative selection of a T cell repertoire
      in the recipient.
AB  - Allo-chimerism and clonal elimination of self antigen (Ag) (Ia + Mls-1a) reactive
      V beta 6+ T cells were analyzed and compared between allogeneic bone marrow (BM)
      chimeras reconstituted with BM cells which had been treated with anti-Thy-1
      monoclonal antibody (mAb) plus complement (C) (T- chimeras) and BM chimeras which
      had been reconstituted with BM cells pretreated with anti-Thy-1 mAb alone (T+
      chimeras). When lethally irradiated AKR (Mls-1a) mice were reconstituted with BM
      cells from B10 or B10 H-2 congenic mice, both T+ and T- chimeras were entirely
      free of signs of graft-versus-host reaction (GVHR). However, complete replacement
      of the AKR lymphoid tissues by donor BM cells was accomplished at an early stage
      in T+ chimeras but not in T- chimeras. On the other hand, clonal elimination of V
      beta 6+ T cells reactive to the recipient Ag (Mls-1a) was abolished in T+
      chimeras but successfully induced in T- chimeras. The V beta 6+ T cells not
      eliminated in T+ chimeras showed depressed responses against Mls-1a antigens. The
      findings herein demonstrate that T cells which contaminate a BM inoculum survive
      in recipient mice after treatment with anti-Thy-1 mAb without C in vitro followed
      by BMT. The surviving T cells have been estimated to represent fewer than 0.5% of
      the BM cells inoculated. These cells appear to accelerate the full replacement of
      recipient lymphoid tissues by donor cells. Furthermore, the T cells which survive
      in the marrow inoculum influence eventually the development of a tolerant state
      in the T cell repertoire of the donor.

PMID- 8295568
TI  - Murine endothelial cell line cells, F-2: interaction with leukocytes and
      cytokines production.
AB  - Flowcytometry demonstrated that murine endothelial cell line F-2 expresses MHC
      class I antigen, FcR II, Mac-1 and vascular cell adhesion molecule-1 (VCAM-1),
      but not intercellular adhesion molecule-1 (ICAM-1) and class II antigen. However,
      co-culturing with TNF-alpha for 24 hr resulted in the increased expression of
      ICAM-1, and the decreased expression of VCAM-1. IL-1 alpha and IFN-gamma exerted
      this regulatory effect on VCAM-1 but not on ICAM-1. T (Con A blast) and B (LPS
      blast) cells adhered to F-2 cells at almost equal levels, and the adhesion was
      enhanced 20 to 50% when the cells were precultured with TNF-alpha for 24 hr. The
      inhibition assay using either (anti-ICAM-1 + anti-LFA-1, lymphocyte function
      associated antigen-1) or (anti-VCAM-1 + anti-VLA-4, very late antigen-4) mAbs
      demonstrated that the ICAM-1 system was utilized more preferentially by T than B
      blasts when F-2 cells were stimulated with TNF-alpha, and the VCAM-1 system was
      vice versa under the unstimulated and stimulated conditions. Granulocytes also
      adhered to F-2 cells, but no mAbs could inhibit the adhesion. Although F-2 cells
      produced a considerable amount of IL-6, GM-CSF and neutrophil chemotactic
      activity, a 24 hr incubation with TNF-alpha resulted in an increase of 12 fold in
      IL-6 and 3 fold in neutrophil chemotactic activity production.

PMID- 8295569
TI  - Preliminary observations on ultrastructure of borreliae in tissues of Ixodes
      persulcatus.
AB  - We observed Lyme borrelia by electron microscopy in the tissues of the ticks,
      Ixodes persulcatus, which were indicated positive for borreliae by BSK cultures
      of their internal organs. Borreliae (0.25 micron in diameter) were found only in
      the lumen of the midgut. They were closely associated with the microvilli on the
      midgut epithelium but never penetrated into the epithelial cells. Ultrastructural
      features common to Lyme borreliae., i.e., the three-layered membranes surrounding
      the cytoplasm and orientation of the flagella insertions, were obviously
      confirmed. The present results are useful to understand tick tissue-borrelia
      interface.

PMID- 8295570
TI  - Molecular characterization of human rotavirus VP4 genes by polymerase chain
      reaction and restriction fragment length polymorphism assay.

PMID- 8295571
TI  - A place for general medicine among the subspecialties.

PMID- 8295572
TI  - Endoscopic carpal tunnel release.

PMID- 8295573
TI  - Endoscopic carpal tunnel release. Use of the modified Chow technique in 215
      cases.
AB  - OBJECTIVE: To present my experience using the modified Chow two-portal technique
      of endoscopic carpal tunnel release. PATIENTS: Two hundred and fifteen patients
      with a clinical diagnosis of carpal tunnel syndrome of more than three months'
      duration, unresponsive to conservative treatment. Only those few with the
      specific contraindications of recurrence, a florid flexor tenosynovitis or an
      acute crush injury were excluded. INTERVENTION: The operation used the modified
      Chow two-portal endoscopic method of carpal tunnel release. The original Chow
      method was used in another 15 patients. MAIN OUTCOME MEASURE: Symptomatic relief
      of pain and paraesthesia. RESULTS: Most patients made a rapid and dramatic
      recovery, with an early return to work, when compared with both my and patients'
      previous experience of open carpal tunnel release. Complications were few--two
      cases of mild reflex sympathetic dystrophy, two of unrelieved symptoms, and no
      permanent nerve or tendon injury. CONCLUSION: The modified Chow two-portal
      technique of endoscopic release of the carpal tunnel is effective, with a rapid
      recovery and few complications--provided that it is done by a surgeon experienced
      in this method.

PMID- 8295574
TI  - Bier's block--the experience of Australian emergency departments.
AB  - OBJECTIVE: To describe the current use, effectiveness and safety of Bier's block
      within Australian emergency departments. DESIGN: A review of clinical practice
      based on an opinion survey of directors of emergency departments. PARTICIPANTS:
      Directors of 120 private and public hospital emergency departments. RESULTS: A
      response rate of 97% was achieved. Bier's block was used in 67% of Australian
      emergency departments. Emergency department medical staff performed the procedure
      in 83% of these hospitals. It was estimated that 7500 emergency department Bier's
      blocks were performed each year. Ninety-six per cent of respondents found Bier's
      block to produce adequate regional anaesthesia. Reported complications or adverse
      reactions were extremely rare. A wide variation in procedural approach was
      evident. CONCLUSIONS: Bier's block is a popular, reliable and relatively safe
      anaesthetic technique for use in emergency departments. Increased surveillance of
      local anaesthetic morbidity associated with the technique, as well as a
      standardisation of the procedure in the emergency department setting, are
      required.

PMID- 8295575
TI  - Youth suicide in Victoria: a retrospective study.
AB  - OBJECTIVE: To determine the trends in youth suicide in Victoria and Australia as
      a whole, and their relation to youth unemployment. DESIGN: We used Australian
      Bureau of Statistics data to analyse suicide trends between 1907 and 1990 in
      young people aged 15-24 years and made an in-depth study of youth suicides
      between 1980 and 1990, for which computerised data are available. RESULTS: There
      has been a steady increase in youth suicide both in Victoria and Australia as a
      whole since 1960 in males but not females. There were significant differences in
      age, sex and area of residence in both the rate and the method of suicide. The
      increase in youth suicide was not associated with the rise in unemployment. Male
      (not female) suicide rates were higher in non-metropolitan areas and areas of
      high youth unemployment. The reasons for the increase in youth suicide remain
      obscure. CONCLUSIONS: There is a need for a prospective in-depth study to
      determine factors in the aetiology of youth suicide, with particular reference to
      possible areas for prevention.

PMID- 8295577
TI  - Tiaprofenic acid as a cause of non-bacterial cystitis.
AB  - OBJECTIVE: To draw attention to a relationship between the taking of tiaprofenic
      acid (Surgam) and the development of severe non-bacterial cystitis. DESIGN: Seven
      case reports. PATIENTS: Six women and one man aged between 62 and 83 years with
      severe chronic cystitis who were taking tiaprofenic acid regularly for
      osteoarthritis. Six of the seven had initially been diagnosed as having
      interstitial cystitis. RESULTS: All patients had classic symptoms and minimal
      signs on physical examination of chronic cystitis but urinalyses showed sterile
      pyuria, microscopic haematuria and proteinuria. Their upper urinary tracts were
      normal. All had severe and diffuse mucosal inflammation noted on cystoscopy,
      which became more marked with distension. Histological examination of bladder
      biopsies showed severe acute and chronic inflammation. Symptoms were present for
      an average period of six months, resulting in great morbidity. All patients
      recovered completely after the withdrawal of tiaprofenic acid within four to
      eight weeks (average 5.7 weeks). CONCLUSION: A strong case for a cause-and-effect
      relationship between tiaprofenic acid and non-bacterial cystitis has been
      presented and a clinical pattern of disease established. Awareness of this
      condition is needed to reduce its morbidity in the community and to remove the
      need for expensive investigations.

PMID- 8295576
TI  - Epidemiology of multiple sclerosis in Australia. With NSW and SA survey results.
AB  - OBJECTIVES: (i) To determine the prevalence of multiple sclerosis (MS) in New
      South Wales and South Australia; (ii) to compare these prevalences with those in
      other areas of Australia and to determine the relationship between prevalence and
      latitude; (iii) to examine the relative contribution of genetic and environmental
      factors in the aetiology of the disease in Australia; and (iv) to ascertain
      whether there had been a change in the frequency of the disease since 1961.
      RESULTS: The crude prevalence of MS in New South Wales on prevalence day
      (National Census Day, 30 June 1981) was 37.2/100,000 and the age-standardised
      prevalence 36.6/100,000. The female:male ratio was 2.3:1. The crude prevalence in
      South Australia was 29.4/100,000 and the age-standardised prevalence
      28.8/100,000. The female:male ratio was 2.4:1. No Aborigines or Torres Strait
      Islanders with MS were identified. There was a significant increase in the
      prevalence with increasing south latitude in Australia, MS being about seven
      times more frequent in Hobart than in tropical Queensland, but no genetic
      differences were found in the surveyed population in different parts of
      Australia. A significant increase in the prevalence of MS occurred in most areas
      of Australia between 1961 and 1981, but this may not reflect a true increase in
      incidence. CONCLUSION: The increasing prevalence with increasing south latitude
      cannot readily be explained by genetic susceptibility, and suggests that
      environmental factors are important for expression of the disease.

PMID- 8295578
TI  - Carbamazepine-induced pneumonitis.
AB  - OBJECTIVE: To present a case of a rare pulmonary reaction to carbamazepine.
      CLINICAL FEATURES: One month after starting carbamazepine therapy, a previously
      well 38-year-old man developed pulmonary interstitial pneumonitis associated with
      debilitating systemic symptoms, the cause of which was not diagnosed for a
      further three months. Transbronchial lung biopsy showed granulomatous
      inflammation consistent with an allergic drug reaction. INTERVENTION AND OUTCOME:
      The patient's clinical status, chest x-ray appearance and arterial blood gas
      tensions all normalised after withdrawal of the drug without any specific
      therapy. CONCLUSION: Pneumonitis is a rare adverse reaction to carbamazepine
      therapy. However, awareness may reduce delays in both diagnosis and withdrawal of
      the drug.

PMID- 8295579
TI  - Autopsy evidence of pulmonary thromboembolism.
AB  - OBJECTIVE: To determine the prevalence of pulmonary thromboembolism (PE) and
      underlying risk factors at autopsy, compared with clinical diagnosis. DESIGN:
      Retrospective review of autopsy records, death certificates and medical
      histories. PATIENTS AND SETTING: All 132 patients who underwent autopsy at St
      Vincent's Hospital, Melbourne, in 1992. RESULTS: Sixteen cases (12% of autopsies)
      of PE were found at autopsy. In only two had PE been recorded on the death
      certificate; in one other, diagnosis had been made before death. Associated
      pulmonary infarction and/or haemorrhage was found in only six patients with PE.
      All 16 had at least one underlying risk factor: advanced age, cancer, heart
      disease, or recent pelvic or abdominal surgery. In four patients with missed PE,
      clinical records showed episodes consistent with PE. There were four false
      positive diagnoses. CONCLUSIONS: Significant undiagnosed pulmonary embolism is
      not uncommon at autopsy. Many episodes are clinically silent, but the diagnosis
      should be suspected in at-risk patients with unexplained episodes of dyspnoea and
      tachycardia.

PMID- 8295580
TI  - Organic nitrate therapy for angina pectoris.

PMID- 8295581
TI  - Further to "the further fate of the foreskin". Update on the natural history of
      the foreskin.
AB  - The fortunate foreskin of an infant boy will usually be left well alone by
      everyone but its owner. Problems such as phimosis are not common, and can usually
      be treated medically without resort to circumcision.

PMID- 8295582
TI  - Victorian public hospitals: taking a sledgehammer...?
AB  - Until relatively recently, there have been few attempts to introduce strong forms
      of competition into publicly funded hospital systems, whether in Australia or
      elsewhere. The Victorian government has done so by implementing a casemix funding
      formula from July 1993 and in the process has foreshadowed that the least
      efficient hospitals will close. While it is of vital importance to improve the
      efficiency of Australian hospitals, and a key factor is to use casemix funding to
      achieve microeconomic reform, it is not appropriate to use competition to close
      hospitals. Arguments against using marketplace forces to determine the fate of
      hospitals include: the difficulties that could ensue with an inappropriate
      distribution of hospitals in Victoria; the necessity to provide hospital services
      for the public good; whether reducing the public sector is actually economically
      beneficial; and the conclusion reached by many in the United States, that health
      care should not be treated as a commodity. I argue for the development of a more
      sophisticated policy than one which uses the principles of laissezfaire and
      relative efficiency to close public hospitals.

PMID- 8295583
TI  - Travel medicine. 1. Before departure.

PMID- 8295584
TI  - Vascular surgery.

PMID- 8295585
TI  - The pros and cons of transdermal nicotine therapy.
AB  - OBJECTIVE: To review current knowledge of the efficacy, safety and cost of
      transdermal nicotine therapy for smoking cessation. DATA SOURCES AND STUDY
      SELECTION: 1. Published and unpublished reports of randomised, double-blind
      trials of at least 12 weeks' duration, in smokers motivated to cease smoking,
      identified by a search of the MEDLINE database, article and book bibliographies,
      Current contents, and by a request to the Medical Department of Ciba-Geigy
      (Australia) Ltd. 2. A clinical trial of 1500 smokers using transdermal nicotine
      (S Gourlay, unpublished data). DATA SYNTHESIS: Transdermal nicotine more than
      doubles the success rates of smoking cessation attempts in motivated subjects who
      smoke at least 10-15 cigarettes per day (odds ratio 12 months after quitting,
      2.3; 95% confidence interval, 1.6-3.4). Application site reactions are not
      uncommon (erythema or burning < or = 16%, transient itch < or = 50%) and cause
      discontinuation of therapy in up to 10% of subjects. Sleep disturbance due to
      nocturnal nicotine absorption occurs in up to 13% of subjects when patches are
      worn overnight. Smoking or nicotine chewing gum used concurrently with
      transdermal nicotine could raise peak nicotine levels but is unlikely to
      adversely affect individuals with established tolerance to nicotine. Smoking and
      (theoretically) nicotine replacement therapies should be avoided in pregnancy or
      patients with unstable coronary artery disease. In such patients, the risk
      benefit ratio of nicotine replacement therapies may be favourable for nicotine
      dependent smokers unable to cease smoking by alternative methods. CONCLUSIONS:
      Transdermal nicotine is an effective smoking cessation therapy for motivated,
      nicotine-dependent smokers. As most smokers can cease smoking on their own, and
      the patches are costly, they should be recommended only for smokers who are
      unable to quit by simpler means and those likely to suffer severe nicotine
      withdrawal symptoms.

PMID- 8295586
TI  - Mycobacterium ulcerans infection on Phillip Island, Victoria.

PMID- 8295587
TI  - Anaphylaxis after skin tests.

PMID- 8295588
TI  - Undiagnosed post-traumatic stress disorder following motor vehicle accidents.

PMID- 8295590
TI  - Whither genetic services?

PMID- 8295589
TI  - The ongoing assessment of techniques of laparoscopic hernia repair.

PMID- 8295591
TI  - The calcium controversy revisited: implications of new data.

PMID- 8295592
TI  - Diagnostic procedures and health outcomes. Upper gastrointestinal tract
      investigation in the elderly.

PMID- 8295593
TI  - Nosocomial hypothermia in the tropics.

PMID- 8295594
TI  - Hepatitis B vaccination in the skin penetration industry.

PMID- 8295595
TI  - Uptake of Hib vaccination in long-term day care centres in Perth, Western
      Australia.

PMID- 8295596
TI  - The adequacy of management of women with CIN 2 and CIN 3 Pap smear abnormalities.

PMID- 8295597
TI  - Prevention of HIV and HBV transmission in general practice.

PMID- 8295598
TI  - Elective term in Kiribati.

PMID- 8295599
TI  - Achieving better health in Australia in the next five years.

PMID- 8295600
TI  - The hazards of utility poles.

PMID- 8295601
TI  - Day stay, ambulatory or outpatient surgery.

PMID- 8295602
TI  - [Problems and complications after implantation of automatic defibrillators].
AB  - Until now there are only few reports about problems and complications associated
      with the automatic implantable cardioverter-defibrillator (ICD). Therefore, we
      studied the follow-up of 295 patients, who underwent ICD therapy. Epicardial ICD
      implantation was performed in 206 patients (71%) and 89 patients (29%) received
      transvenous ICD systems. Infections or seroma of the pulse generator and/or lead
      systems were observed in 18 patients (6%), in nine patients after first ICD
      implant and in nine patients after generator replacement. General signs of
      inflammation were present in eleven patients, whereas local signs with seroma of
      the pocket were observed in seven patients. Explantation of the entire ICD
      hardware was performed in eleven patients and seven patients underwent partial
      removal of the ICD system. Lead complications occurred in 15 patients (5%), in
      eleven patients with epicardial and in four with transvenous ICD systems. All
      patients had inappropriate ICD shocks and had to undergo lead replacement.
      Inappropriate ICD shocks due to supraventricular tachyarrhythmias occurred in 24
      patients (8%). Other complications (apoplexia, hematoma, pneumothorax) were
      observed in 15 patients (5%). Our data show that complications associated with
      the ICD are low. However, these complications can cause big problems and need
      appropriate diagnosis and treatment.

PMID- 8295603
TI  - [Type II diabetes (NIDDM): overview of the preclinical and clinical status
      exemplified by the patient sample of a general hospital in a rural district].
AB  - From unselected patients of a general hospital 198 patients with diabetes
      mellitus type II (NIDDM) were registrated between May and December 1990 by means
      of a standardized questionnaire and with the help of standardized clinical
      diagnostics epidemiological as well as anamnestic and clinical data were
      collected. In the great majority of the cases, the only therapeutical approach
      consisted in medical treatment, most commonly lacking dietary advices. The
      patients knowledge concerning diabetes and dietary treatment strongly correlated
      with the participation in specific education courses in the past. There was a
      high incidence of relevant concomitant diseases and pathological appearances
      succeeded to the diabetes mellitus. In view of the actually pronounced risk
      factors and concomitant diseases the importance of a "metabolic syndrome" becomes
      evident alluding to consequences in diagnosis and treatment. With regard to
      public health aspects and financial implications extensive education and training
      programs, especially in the field of ambulant care, seem to be necessary. Rising
      prevalence- and incidence rates of the diabetic disease claim, besides preventive
      means, for initiative in this subject.

PMID- 8295604
TI  - [Treatment of migraine attacks: combination of dihydroergotamine tartrate and
      paracetamol in comparison with individual drugs and placebo].
AB  - BACKGROUND AND METHODS: In a multi-center, double-blind, placebo-controlled
      crossover study safety and efficacy of oral dihydroergotamine tartrate (DHE) 2
      mg, paracetamol 1000 mg, and a fixed combination of these two agents was compared
      for the relief of migraine attacks. The effect of the four different treatments
      on severity and duration of migraine headache was assessed pretreatment and at
      one and two hours post-treatment in the patient diary (10 point numerical rating
      scale 0 = no pain, 9 = unbearable pain). Nausea, vomiting, photophobia,
      phonophobia, and adverse events were also recorded in the patient diary. RESULTS:
      For 288 patients (81% female, 19% male) of 474 enrolled the results of four
      consecutive migraine attacks could be evaluated; 186 patients were excluded from
      the analyses because of missing data or protocol violations. Compared with
      placebo, headache severity was significantly reduced after all three treatments
      at one and two hours and all three treatments resulted in statistically
      significant rapid relief of pain, proving a superior effect of the combination
      over the mono agents. Duration of headache was significantly shorter when the
      combination was taken and the number of patients having either no headache or a
      reduction of pain of more than 50% after one and two hours was bigger in the
      combination group. Eight adverse events were experienced in patients during
      placebo treatment, seven in patients during treatment with the fixed combination,
      five in patients during DHE treatment and two in patients during paracetamol
      treatment. All adverse events were transitory and none was serious. CONCLUSION:
      The oral combination of 2 mg DHE and 1000 mg paracetamol is safe and effective in
      the treatment of acute migraine attacks and should be first choice of therapy in
      patients who do not respond to mild analgesics like paracetamol alone.

PMID- 8295605
TI  - [76-year-old patient with lower intestinal hemorrhage in infrarenal aneurysm of
      the abdominal aorta and ileum carcinoid tumor].

PMID- 8295606
TI  - [Medical ethics in the medical-industrial complex].

PMID- 8295607
TI  - [Contribution of internal medicine to education of medical students].

PMID- 8295608
TI  - [Asymptomatic perforation of the esophagus after C6/C7 plate osteosynthesis].

PMID- 8295609
TI  - [Symposiums of the 99th Congress of the German Society of Internal Medicine.
      Nutritional therapy].

PMID- 8295610
TI  - [Position of the German Society of Internal Medicine on the "Recommendations for
      organization of medical education by the expert committee regarding reform of the
      medical curriculum" by the Federal Health Office 12 November 1992].

PMID- 8295611
TI  - The Health Security Act of 1993. A blueprint for reform.

PMID- 8295612
TI  - Current and future HIV/AIDS clinical research. HIV-related therapy improving-
      slowly.
AB  - More than 300,000 cases of AIDS have been reported in the United States since
      1981. Despite major scientific advances and much effort, the benefits of
      treatment have been modest. The variable nature of the human immunodeficiency
      virus (HIV) and the complexity of the immune system are the major obstacles to
      advances in treatment. This article summarizes the current state of clinical
      research in pursuit of improved HIV therapy and takes a look into the future of
      anti-HIV therapeutics. It also provides an overview of HIV clinical research
      underway in Minnesota. Research efforts to improve therapy of HIV-induced immune
      deficiency will involve three strategies: better anti-HIV drugs and combinations
      of drugs aimed at slowing the replication of HIV, immune-based therapies intended
      to stimulate the immune system, and multiple opportunistic pathogen prophylaxis
      strategies to prevent HIV-related opportunistic infections. This approach will
      involve considerable cost and polypharmacy. Improvements in HIV/AIDS therapy are
      likely to occur incrementally, but the endeavor needs widespread support from
      patients, physicians, and the public. For now, the best strategy is prevention,
      which is where physicians can have the greatest impact on the epidemic.

PMID- 8295613
TI  - Counseling patients for routine HIV testing AMA guidelines. MMA Committee on
      Ethics and Medical-Legal Affairs.

PMID- 8295614
TI  - CLIA '88 laboratory inspections. Prepare and survive.

PMID- 8295615
TI  - MMA supports goals of Clinton plan. Physicians still concerned about details.

PMID- 8295616
TI  - Aminoglycosides may block HIV replication.

PMID- 8295617
TI  - Needle exchange programs help prevent AIDS.

PMID- 8295618
TI  - Criterion HealthCare Network. Making clinics without walls a reality. Interview
      by Joseph M. Moriarity.

PMID- 8295619
TI  - [IMK-B manipulators for implantology. The Micro Mega experience is repeated].

PMID- 8295620
TI  - [An ultrastructural analysis of dentin treated with chemical agents].
AB  - Dental last generation bonding systems require the total removal of smear layer
      and smear plug by chemical solutions. Intermediate fluid resin can penetrate the
      dentinal tubes obtaining a better anchorage to the dental structures. The
      department of Operative dentistry of the University of Rome "La Sapienza" has
      carried research observing by means of the SEM the ultrastructural aspect of
      smear layer and the effect of dentin treatment with five different chemical
      agents.

PMID- 8295621
TI  - [Microanalytical determinations of gold alloys for fixed dentures].
AB  - In this work the authors analyse gold alloys for fixed prosthesis by X-ray
      spectrometry in energy dispersion (EDS). The results of this analysis, given in
      graphic and table form, show remarkable differences in alloy composition. For
      this reason recommended dentists are to be attentive and severe in the control of
      gold alloys for fixed prosthesis.

PMID- 8295622
TI  - [The growth of certain craniofacial dimensions in regard to the development of
      normal occlusion and malocclusion in the period of mixed dentition].
AB  - The authors have analysed the growth of the craniofacial parameters zygion
      zygion, eurvon-eurvon, glabella-opisthocranion, nasion-gnathion and nasion
      prosthion with examinees aged 5 to 13 years with normal occlusion and
      malocclusion. No statistically significant differences in the growth of the
      analysed parameters in regard to the constancy or change of the examinee's
      orthodontic diagnosis in the period of mixed dentition have been found.

PMID- 8295623
TI  - [Clinico-statistical observations on 292 cases of salivary gland pathologies].
AB  - 292 cases of salivary gland diseases have been observed and treated at the Oral
      and Maxillo-Facial Surgery Department of the Faculty of Medicine II Naples
      University. The statistical results concerning age, sex, localization,
      histological characteristics and therapy are analysed and compared with other
      references.

PMID- 8295624
TI  - [A microbiological evaluation of the use of roxithromycin in oral odontogenic
      infections].
AB  - Odontogenic infections are the primary infections caused by indigenous oral
      bacteria, when a factor changes their perfect equilibrium. We studied 30 samples
      from patients with odontogenic infections that were submitted to therapy with
      roxithromycin. Our results showed that 79% of aerobic and 71% of anaerobic
      bacteria, responsible for odontogenic infections, were sensitive to
      roxithromycin.

PMID- 8295625
TI  - Reported vaccine-preventable diseases--United States, 1993, and the childhood
      immunization initiative.
AB  - In the United States, children are routinely vaccinated against nine diseases-
      diphtheria, Haemophilus influenzae type b (Hib), hepatitis B, measles, mumps,
      pertussis, poliomyelitis (paralytic), rubella, and tetanus. Based on public
      health surveillance and epidemiologic assessment of most of these diseases, the
      impact of childhood vaccination on reported occurrence has been substantial:
      provisional surveillance data for 1993 indicate that for five of these diseases
      and for congenital rubella syndrome (CRS), the number of reported cases is at or
      near the lowest levels ever, suggesting near interruption of transmission of
      these diseases. This report presents provisional data for December 1993 for these
      10 diseases, compares provisional data for 1993 with final data for 1992, and
      describes the Childhood Immunization Initiative (CII).

PMID- 8295626
TI  - Prevalence of adults with no known major risk factors for coronary heart disease-
      behavioral risk factor surveillance system, 1992.
AB  - Although the death rate for coronary heart disease (CHD) in the United States has
      declined approximately 50% since 1970, CHD remains the leading cause of death for
      both men and women and, in 1990, accounted for 489,340 deaths. National
      strategies and programs have targeted individual risk factors for death
      attributed to CHD. However, an alternative approach may be to measure the
      prevalence of adults who have no known risk factors for CHD. This report provides
      state-specific estimates of and characterizes adults who report having no known
      major risk factors for CHD.

PMID- 8295627
TI  - Update: dracunculiasis eradication--Mali and Niger, 1993.
AB  - Mali and Niger, countries in West Africa, ranked sixth and eighth in the number
      of reported cases of dracunculiasis (i.e., Guinea worm disease) in 1992. In March
      1993, Global 2000, Inc., and the World Health Organization (WHO) Collaborating
      Center for Research, Training, and Eradication of Dracunculiasis at CDC began
      providing direct assistance for the eradication of dracunculiasis in both
      countries by assigning a resident public health advisor to each country. This
      report summarizes surveillance data for the two countries during 1991-1993 and
      describes their progress toward eradication of dracunculiasis.

PMID- 8295628
TI  - State cancer registries: status of authorizing legislation and enabling
      regulations--United States, October 1993.
AB  - Population-based cancer registries have identified cancer incidence rates
      indicating that the burden of cancer in the United States is substantial and
      varies widely by geographic location and ethnicity. However, for most existing
      state cancer registries, resources are inadequate for insuring minimum standards
      for quality and for completeness of case information. In October 1992, Congress
      enacted the Cancer Registries Amendment Act* that authorized CDC to establish a
      national program in support of cancer registries. The goal of this program is to
      enhance existing state cancer registries and to help establish statewide cancer
      registries so that all states have population-based cancer registries meeting
      minimum standards for completeness, timeliness, and quality. To ensure complete
      and timely reporting of newly diagnosed cases of cancer, the federal statute
      requires authorization of cancer registries under state-specific laws and
      promulgation of regulations that ensure case reporting and use of data for
      research. This report extends efforts by the National Cancer Institute to assess
      existing state laws and regulations to determine how they compare to state
      specific legislation required in the cancer registries act.

PMID- 8295629
TI  - Mortality from congestive heart failure--United States, 1980-1990.
AB  - In the United States, congestive heart failure (CHF) was the underlying cause of
      death for approximately 38,000 persons in 1990; of those deaths, approximately
      92% were among persons aged > or = 65 years. CHF, a clinical syndrome defined as
      a chronic inadequate contraction of the heart muscle resulting in insufficient
      cardiac output, is a manifestation of one or more underlying conditions,
      including systemic or pulmonary hypertension or a history of other heart diseases
      (e.g., myocardial infarction, atherosclerosis, cardiomyopathy, congenital heart
      disease, or rheumatic fever). The long-term prognosis of CHF depends on the
      underlying condition and the response of that condition to treatment. Despite
      declines in death rates for ischemic heart disease and cerebrovascular disease,
      improvements in detection and treatment of hypertension, and considerable
      advances in the diagnosis and management of CHF, mortality from CHF has increased
      since 1980. This report summarizes trends in CHF mortality in the United States
      during 1980-1990 and presents state-specific mortality data for 1990 (the most
      recent year for which such data are available).

PMID- 8295630
TI  - Foodborne outbreaks of enterotoxigenic Escherichia coli--Rhode Island and New
      Hampshire, 1993.
AB  - Infections with enterotoxigenic Escherichia coli (ETEC) are a frequent cause of
      diarrhea in developing countries but not in the United States and other
      industrialized countries. This report describes two foodborne ETEC outbreaks that
      occurred in the United States in 1993.

PMID- 8295631
TI  - Continued use of drinking water wells contaminated with hazardous chemical
      substances--Virgin Islands and Minnesota, 1981-1993.
AB  - Improperly disposed hazardous chemical substances are a common source for
      contamination of drinking water wells. The Agency for Toxic Substances and
      Disease Registry (ATSDR) and other environmental and public health agencies have
      recommended that exposure-reduction procedures (i.e., provision of alternative
      water supplies and construction of new water supplies) be implemented when
      drinking water wells are contaminated with hazardous substances in concentrations
      that approach or exceed levels potentially associated with adverse health
      outcomes in humans. Once these procedures are implemented, the original wells
      should not be used as sources for drinking water. This report summarizes two
      cases in which contaminated drinking water wells were being used even though
      health advisories had been issued to discontinue use of the wells.

PMID- 8295632
TI  - Limited availability of penicillin G sodium.

PMID- 8295633
TI  - Modeling growth and individual differences in spatial tasks.
AB  - The goal of the present research is to understand individual differences and
      growth of children's and adolescents' performance on two spatial tasks through a
      formal model framework. In Study 1, 579 subjects aged 7-16 years old drew lines
      to represent their water-level task predictions for eight tilted rectangular
      vessels. In the verticality task, called the "van task," subjects drew lines
      representing their predictions concerning the orientation of a plumb line
      suspended from the ceiling of a van parked on eight different inclines. In Study
      2, 185 subjects aged 9-16 years were presented with video displays on a computer
      monitor and were instructed to adjust lines on the screen to indicate their
      predictions for the same stimuli used in Study 1. Later, they responded to a
      multiple-choice verbal analogies test and answered interview questions concerning
      their task performance strategies for the van and water-level tasks. In both
      studies, responses on the van and water-level tasks were scored as correct or
      incorrect on the basis of empirically derived scoring criteria that varied with
      age. The number of correct responses for each subject on the van and water-level
      tasks was modeled as a binomial random variable. Individual differences, growth
      differences, and sex differences in task performance were modeled as mixtures of
      binomial distributions, a model that may be viewed as a latent class model. Data
      for Study 1 subjects 11 years and older were combined so that the joint structure
      of the water-level and van tasks could be studied. This structure was modeled as
      a mixture of bivariate binomial distributions. On the basis of their task
      performance, subjects in Study 1 were assigned to their corresponding latent
      classes. Once classified, the original response distributions of subjects within
      each latent class were explored in an effort to understand their various response
      strategies. Additionally, the correspondence between verbal explanations and van
      and water-level task performance was investigated in Study 2. Results include the
      following: 1. A two-component binomial mixture distribution fit well the van and
      water-level task data for each age and sex group; each binomial component may be
      viewed as a different latent class. Variance accounted for under the model often
      exceeded 90%. One binomial component (latent class) modeled the poor performers
      with poor task success rates, and the second component modeled the remaining good
      performers who consistently performed well.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8295634
TI  - [Obstruction jaundice in 2 young women: cysts or malignity?].

PMID- 8295635
TI  - [Current aspects of Alzheimer's disease].

PMID- 8295636
TI  - [Psychological and social problems in family practice: a matter of competence and
      autonomy in physicians and patients].

PMID- 8295637
TI  - [Prevalence, indication and course of depression in family practice].

PMID- 8295638
TI  - [Mental problems in family practice more variable and diffuse that in
      psychiatry].
AB  - OBJECTIVE: To describe the epidemiology of mental problems in general practice,
      from the viewpoint of the general practitioner (GP). DESIGN: Descriptive
      population survey. SETTING: Data were collected from the National Study of
      Morbidity and Interventions in General Practice. METHOD: In 1987-1988 we used an
      interview to assess health status and medical consumption of 10,350 persons, aged
      15 and over. At the same time they were screened for mental illness using the
      General Health Questionnaire (GHQ). For three months, all doctor-patient
      contacts, the reason for contact (classified in ICPC) and the GP's assessment of
      possible psychological factors in the reason for contact were recorded. RESULTS:
      Of the patients with a high GHQ score only one third explicitly mentioned his
      psychological problems to the GP, 70 were recognized by the GP as having
      psychological problems in the three month period and besides psychological
      problems this group showed much more acute and chronic physical illness. Patients
      scoring high on the GHQ have more symptoms, but in general not other symptoms
      than mentally 'healthy' people have. CONCLUSION: Screening-programmes on mental
      illness are not recommended because of the impossible of determining the groups
      at risk. Prevention might be possible in patients with a high frequency in doctor
      patient contacts and many physical complaints. A public health approach,
      encouraging patients to discuss psychological problems directly with their GP,
      might be sensible.

PMID- 8295639
TI  - [Unterberger's test not useful in testing of vesitibular function].
AB  - OBJECTIVE: Quantification of the stepping test in routine neurological
      examination. SETTING: University Hospital Groningen, the Netherlands. DESIGN:
      Prospective, controlled study. METHODS: The stepping test was assessed in 41
      healthy subjects, in 7 subjects with artificially induced vertigo and in 83
      patients with disturbances of gait or equilibrium resulting from different
      affections of the central nervous system. Displacement and rotation to the right
      or the left side were measured. The different groups were then compared with each
      other. RESULTS: We found a great inter- and intra-individual variation in
      direction and width of rotation and in displacement. The results of the test are
      not influenced by right(+)-or left(-)-handedness or by dominance of the right or
      the left leg. CONCLUSION: The current test does not appear to be useful for
      detection of abnormalities in the vestibular system or for distinguishing normal
      individuals from patients.

PMID- 8295640
TI  - [Rapid cycling in bipolar disorders].
AB  - Two patients, a woman aged 32 and a man aged 27 years, were suffering from rapid
      cycling bipolar disorder (i.e. a course with four or more episodes a year).
      Hypothyroidism and the use of antidepressants may be involved in the development
      of such a disease course. Treatment with carbamazepine was successful in both
      patients. Patients suffering from rapid cycling bipolar disorder should be
      treated with lithium or carbamazepine, or a combination of these. Antidepressants
      should only be used with great caution.

PMID- 8295641
TI  - [Bronchiectases; clinical aspects, diagnosis and treatment].
AB  - Localised bronchiectasis was diagnosed in three immigrants, a male aged 16 and
      two females aged 45 and 20 years old. The symptoms were productive coughing
      (purulent discharge) and (or) haemoptysis. All recovered after surgical resection
      of the diseased lung parts. With the growing population of immigrants in the
      Netherlands it is of great importance to consider the presence of localised
      bronchiectasis in patients from this population who present with a persistent or
      recurrent bronchopneumonia.

PMID- 8295642
TI  - [Skin disorders caused by bismuth oxide (De-Nol)].
AB  - Since 1982, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs
      received 12 reports of skin reactions attributed to the use of bismuth
      subcitrate. These concerned 6 women and 6 men with a mean age of 39 years, who
      developed skin reactions an average of 2 days after starting treatment with
      bismuth subcitrate: small-patchy or maculopapular exanthema, angioedema,
      erythema. All patients recovered completely after discontinuing the use of
      bismuth subcitrate.

PMID- 8295643
TI  - [Periodic study of families with a hereditary predisposition for breast
      carcinoma].

PMID- 8295644
TI  - [Complications following axillary lymph node excision for breast carcinoma].

PMID- 8295645
TI  - [Neuroanesthesia. Some new aspects].
AB  - Major changes are becoming apparent among neuro-anesthetists and neurosurgeons in
      their attitude towards hypocarbia, blood volume, mean arterial pressure (MAP),
      cerebral perfusion pressure (CPP), anesthetic technique, and brain retraction
      pressure. These changes are related to the transfer from intensive care units to
      operating theaters of major new physiologic data regarding oxygen delivery to
      tissues (DO2) and oxygen consumption by tissues (VO2). These fundamental data
      have progressively, during the last five years, led to the concept of brain
      homeostasis based on four fundamental therapeutic principles: 1) The use of
      moderate hypocarbia (as opposed to deep hypocarbia which should stay
      exceptional). 2) The use of a normal mean arterial pressure (MAP) and thus
      cerebral perfusion pressure (CPP) by promoting a. normovolemia, b. a hematocrit
      around 30% and c. a light anesthesia technique allowing rapid recovery. 3) The
      use of appropriate crystalloids (NaCl 0.9% rather than Ringer-Lactate, and no
      DW5) taking into account measured osmolality. 4) The optimisation of brain
      relaxation by combining an appropriate anesthetic technique, mannitol, head up
      (and head straight) position, together with a lumbar drainage.

PMID- 8295646
TI  - [Are calcium channel blockers really useful in cerebral aneurysm surgery?].
AB  - Two retrospective series of early operated cerebral arterial aneurysms are
      compared. One series involves 74 patients treated from 1983 to 1987 by vascular
      volume expansion only. The other series involves 75 patients treated from 1987 to
      1990 by vascular volume expansion associated by calcium antagonists (nimodipine
      or nicardipine). The conclusion is that in our experience, calcium antagonists do
      not improve the outcome (mortality, cognition findings and return to work)
      obtained by vascular volume expansion alone. Moreover they put forward that there
      is no difference between the patients treated by nimodipine and those treated by
      nicardipine.

PMID- 8295647
TI  - [Comparison of 2 consecutive series of aneurysmal subarachnoid hemorrhage with or
      without nimodipine and study of the temperature curve].
AB  - A total of 210 consecutive patients with aneurysmal subarachnoid hemorrhage
      (S.A.H.) of any clinical grade admitted from January 1985 through May 1990 were
      retrospectively studied to determine the effect of intravenous Nimodipine on
      survival and functional results and to analyse temperature curve as a prognosis
      factor. The 106 patients admitted from January 1985 through November 1987
      constituted the reference series termed G1. The 104 patients admitted from
      December 1987 through May 1990 and treated with intravenous Nimodipine
      constituted the series termed G2. Of the 210 patients, 172 (82%) could be
      operated on with a similar mean operative delay in both series (G1 = 9.5 days, G2
      = 9.8 days). Of the 210 patients, 153 (73%) survived with an average follow-up of
      111 weeks for G1 and of 64 weeks for G2. Nimodipine treatment was associated with
      a significant increase of survival (11.8%, P = 0.05) which was not the result of
      improved operative technique but of a lower incidence of deaths caused by
      postoperative vasospasm (G1 = 5 deaths, G2 = 0 deaths, P = 0.05) and by
      rebleeding (G1 = 15 deaths, G2 = 5 deaths, P = 0.03). No significant difference
      between the two series G1 and G2 was observed regarding functional results in the
      153 survivors, frequency and seriousness of clinical signs of vasospasm during
      the waiting phase for surgery, radiologic signs of vasospasm on initial and
      second angiography, cerebral infarctus on second C.T.-Scan. Analysis of
      temperature curves of the 210 patients revealed that a delayed fever with a
      plateau pattern was associated with a higher incidence of vasospasm, rebleeding,
      and deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295648
TI  - [Teflon wrapping in cerebral aneurysm surgery. A technical note].
AB  - Wrapping is a well-known alternative technique when clipping the aneurysm is by
      no means possible or when it seems necessary to complete an imperfect clip. In 22
      operated cases of intracranial aneurysm, we recently experienced pledgets of
      Teflon arranged and then fixed by drops of fibrin sealant. We used this technique
      in the following operative circumstances: to reinforce the ectatic base of the
      clipped aneurysm (11 cases); to wrap a pre-aneurysmal ectasia distant from the
      ruptured aneurysm (5 cases); to minimize the compression due to the clip to an
      adjacent cranial nerve or artery (6 cases). So far no complication was noted in
      relation to this technique. We then propose this technique of wrapping or
      interposing Teflon as an alternative to the other well-known techniques using
      autogenous tissue, gelatin sponge, cotton or other synthetic coatings or glue. Up
      to now, no known material received a worldwide approval for its complete
      innocuity and/or efficiency. Nowadays, in neurosurgical microvascular
      decompression and in cardiovascular surgery Teflon is widely and satisfactorily
      used. Its biologic tolerance is known to be good. This may apply in this new
      indication, and we would like recommend its practical use. However, for
      reliability and safety, there is an obvious need for a long-term clinical follow
      up and an experimental controlled study as well.

PMID- 8295649
TI  - [Cervical spondylosis. Resection by oblique transcorporeal approach].
AB  - Spondylosis at the cervical level inducing anterior spinal cord compression is
      generally treated by anterior transcorporeal resection of the osteophytic spurs.
      We report on 12 cases over 2 years in which a new technique has been applied; it
      uses the lateral approach exposing and retracting laterally the vertebral artery;
      then, the vertebral bodies are drilled out obliquely from the anterolateral
      corner to the posterolateral one on the opposite side. The vertebral bodies were
      drilled using this technique on 1 level in 2 cases, on 2 levels in 4, on 3 levels
      in 5 and on 4 levels in 1; the C4-C5, C5-C6 and C6-C7 levels were the most
      frequent sites involved in 9, 8 and 6 cases respectively. No graft or arthrodesis
      was used since the stability of the spine was never compromised. Improvement of
      the neurological symptoms was observed in all the cases with the best results
      achieved on the motor deficit and sphincter disturbances. Every case was
      controlled by dynamic standard radiographies (flexion-extension), CT scan and
      MRI. The results were good in all cases in terms of osteophytes resection, spinal
      cord decompression and spinal stability. This technique of oblique resection of
      the cervical bodies seems quite efficient to alleviate spondylotic compression of
      the spinal cord; moreover, it appears simpler and safer than the anterior route
      since the operative field is much wider with all the vital structures protected
      and retracted medially and bone grafting is never necessary.

PMID- 8295650
TI  - [Retrospective multicenter study of prevention of thromboembolic complications
      after lumbar disk surgery].
AB  - A retrospective study of thromboembolic complications after lumbar disc surgery
      has been performed. It included 16,656 patients from fifty neurosurgical units,
      operated on over the year 1989. The average number of operations was 333 +/- 19.5
      in each unit, their average duration 55.2 +/- 20 minutes, and the hospital care
      6.2 +/- 1.7 days. Surgery was performed using the genupectoral position in 64% of
      the cases, the supine position in 28%, and the lateral position in 8%. Two groups
      of patients have been individualized: a first group of patients with no
      preventive antithrombic treatment (46% of the units) including 10,351 patients, a
      second group (54% of the units) including 6,305 patients and receiving a
      systematic treatment with low molecular weight heparin (4,304 patients) or
      calciparin (1,001 patients) or antiplatelet agents or pentosane polysulfate
      (1,000 patients). 0.63% of the patients (105) had a thromboembolic accident:
      0.65% in the first group (68 cases) and 0.58% in the second (37 cases). No
      statistically significant difference was noticed between the two groups
      concerning pulmonary embolism and/or lower-limb thrombophlebitis. Nevertheless, a
      prospective randomized study would be usefull to corroborate this first data.

PMID- 8295651
TI  - [Peroperative echography in neurosurgery. Its value and applications 10 years
      later].
AB  - Intraoperative ultrasound imaging has many advantages over other imaging methods.
      The authors present their experience from hundred patients over ultrasound
      scanning. A large iconography is exposed. Not only the intracerebral lesions such
      as gliomas or metastases but also abscess or cysts can be controlled or biopsied
      directly. Per-operative ultrasonography is interesting for spinal cord lesions
      and spinal traumas. Ten years from the first utilisation in neurosurgery, the
      method is always used, its cost is low and its practice is very easy.

PMID- 8295652
TI  - [Intramedullary meningeal melanocytoma].
AB  - A primary benign melanotic tumour was resected twice in the thoracic spinal cord
      of a 49-year-old woman. The patient had complained of low back pains, obstipation
      and mictional urgency for two years. She developed a partial Brown-Sequard's
      syndrome at th10-th12 level. The tumour showed the histological and
      immunohistochemical features of a meningeal melanocytoma. The following up was
      marked by tumoral seeding in the lumbosacral region and later in the cerebral
      hemispheres, which lead to death 4 years after the diagnosis. This is a survey of
      the clinical and morphological characteristics of meningeal melanocytoma and
      demonstrates the risk of secondary dissemination of this primary benign tumour.

PMID- 8295653
TI  - Angiotensin II and fluid ingestion in old rats.
AB  - Fluid ingestion was studied in Fischer 344/Brown Norway F1 rats aged 3, 12, 20,
      and 24 months of age. There was an age-related decrease in fluid ingestion when
      fluid intake was measured over 24 h. After water deprivation, 24- and 20-month
      old rats drank less than 3- and 12-month-old rats. Twelve, 20-, and 24-month-old
      rats had less fluid intake associated with food deprivation than did 3-month-old
      rats. Three month old rats drank more fluid after angiotensin II than did 12-, 20
      , and 24-month-old rats when expressed as fluid intake per kg body weight. These
      studies confirm that the rat is a reasonable model to study age-related
      hypodipsia.

PMID- 8295654
TI  - Glucose enhancement of memory in patients with probable senile dementia of the
      Alzheimer's type.
AB  - Attempts to attenuate the severe memory deficits in patients with SDAT have been
      largely unsuccessful, particularly in patients at advanced stages of the disease.
      Recent evidence indicates that glucose administration enhances memory in
      generally healthy aged rodents and humans. The present experiment demonstrates
      that glucose administration improves memory in moderately to severely demented
      patients with probable SDAT. Glucose ingestion significantly enhanced performance
      on several tests including orientation, word recognition and recall, narrative
      prose, and face recognition after glucose ingestion. Thus, the results extend
      enhancement of memory with glucose from generally healthy rodent and human
      populations to patients with probable SDAT.

PMID- 8295655
TI  - Age-related changes in the contents of neuropeptides in the rat brain and
      pituitary.
AB  - beta-Endorphin, Leu-enkephalin, Met-enkephalin, substance P, somatostatin, and
      cholecystokinin were measured in the brain and the pituitary of male Sprague
      Dawley rats aged 3 months, 12 months, and 22 months. beta-Endorphin, Met
      enkephalin and Leu-enkephalin contents in the neurointermediate lobe, and the
      enkephalin levels in the anterior lobe of the pituitary increased with age. The
      increases in contents were both in the day and at night for beta-endorphin and
      Met-enkephalin. However, the increase for Leu-enkephalin content was in the day
      only. Hypothalamic beta-endorphin content decreased with age only in the day.
      beta-Endorphin and Leu-enkephalin contents in the brain stem, and Leu-enkephalin
      levels contents in the cortex decreased with age at night. Leu-enkephalin in the
      striatum decreased with age in the day. There was also an age-related decrease
      for somatostatin and substance P contents in the striatum and the hypothalamus in
      the day, and in cholecystokinin levels in the hippocampus, and the hypothalamus
      at night. It is concluded that there are age differences in neuropeptide levels,
      and that these changes may differ according to diurnal rhythms.

PMID- 8295656
TI  - Characterization of brain samples in studies of aging, Alzheimer's, and other
      neurodegenerative diseases.
AB  - We review current understanding of the clinical and pathologic information needed
      for the determination of optimal brain tissue samples for the conduct of studies
      of Alzheimer's disease (AD). Characteristics that may distinguish AD from other
      dementing disorders are discussed. Selected considerations in the conduct of
      basic neurobiological studies are also outlined. Although the 28 NIA-funded
      Alzheimer's Centers can provide excellent clinical and neuropathological data,
      studies conducted outside these centers should also strive to gather the
      information suggested here. Clinical and neuropathological data should be used
      not only to classify subjects as control or AD, but also as variables that may
      significantly contribute to the analysis of neurobiological data obtained in the
      laboratory.

PMID- 8295658
TI  - DAU 6215, a novel 5-HT3 receptor antagonist, improves performance in the aged rat
      in the Morris water maze task.
AB  - The effects of the new 5-HT3 receptor antagonist, DAU 6215, on aged rats'
      cognition were assessed in the Morris water maze task. Task performance of aged
      animals that received acutely the dose of 10 micrograms/kg IP was not different
      than that of their aged controls treated with the vehicle. Conversely, a repeated
      IP administration of 10 micrograms/kg DAU 6215 for 3 weeks significantly improved
      task performance of the aged animals as compared to that displayed by the old
      rats treated with the vehicle.

PMID- 8295657
TI  - Beta-amyloid accumulation in aged canine brain: a model of early plaque formation
      in Alzheimer's disease.
AB  - We characterized eight aged beagles (maintained from birth in a laboratory
      colony) and one black Labrador using Bielschowsky's, thioflavine S, and Congo red
      staining, and antibodies to the beta-amyloid peptide, dystrophic neurites, and
      other plaque components. All plaques within these canine brains were of the
      diffuse subtype and were neither thioflavine S- nor Congo red-positive. The
      majority of plaques in the entorhinal cortex contained numerous neurons within
      them while plaques in the dentate gyrus did not. beta-Amyloid immunoreactivity
      was also present within select neurons and neuronal processes and was detected as
      a diffuse linear zone corresponding to the terminal fields of the perforant path.
      There was no significant correlation between extent of beta-amyloid accumulation
      and neuron number in entorhinal cortex. Neither tau-1, PHF-1, nor SMI-31
      immunostaining revealed dystrophic fibers, confirming the classification of these
      plaques as diffuse. Canine plaques did not appear to contain bFGF- or HS-positive
      immunostaining. This may explain why neuritic involvement was not detected within
      these canine plaques. It is possible that the beta-amyloid within the canine
      brain has a unique primary structure or may not be in an assembly state that
      adversely affects neurons.

PMID- 8295659
TI  - Effects of a novel melatonin analog on circadian rhythms of body temperature and
      activity in young, middle-aged, and old rats.
AB  - Circadian rhythms of body temperature and activity were recorded in young, middle
      aged, and old rats. A new melatonin analog, S20242, was administered daily around
      the onset of darkness for a 2-week period. Compared to the young animals, there
      was a significant age-related reduction in the amplitude and stability of body
      temperature and activity in both the middle-aged and old rats. In these two
      groups there was an improvement of the circadian rhythm of body temperature as a
      result of daily application of the melatonin analog.

PMID- 8295660
TI  - Production of amyloid-beta-peptide by cultured cells: no evidence for internal
      initiation of translation at Met596.
AB  - It has been suggested that the A beta fragment of the amyloid precursor protein
      in Alzheimer's disease arises from internal translation initiation at Met596 (1).
      Here we use the recently described in vitro model of A beta production and
      secretion (2) to examine this hypothesis. We show that A beta is no longer
      detectable when the beta APP reading frame is destroyed by introduction of frame
      shift mutations that leave the A beta coding region intact. This result strongly
      suggests that internal initiation at Met596 does not contribute significantly to
      the amount of A beta observed.

PMID- 8295661
TI  - Pathological changes in frontal cortex from biopsy to autopsy in Alzheimer's
      disease.
AB  - We evaluated the change in density of total senile plaques, plaque subtypes, and
      neurofibrillary tangles, from biopsy to autopsy in left frontal cortical sections
      from four patients with clinically typical Alzheimer's disease (AD). Comparisons
      were made on sections stained with modified Bielschowsky and Thioflavin S. In two
      cases, comparisons were also made on tissue stained with a monoclonal Alz-50
      antibody and an antiserum to A beta (beta-amyloid protein). Despite a marked
      decline in mental status over several years of follow-up clinical evaluations,
      there was no consistent significant change in numerical density of plaques or
      tangles among the four cases. However, we did find fewer primitive plaques in the
      autopsy specimens. These results from longitudinally evaluated persons with
      typical AD suggest that although plaques and tangles may serve as adequate
      markers of the presence of AD, their numerical density within a single
      neocortical region may not reflect dementia severity. This conclusion supports
      the results of recent cross-sectional studies on the progression of pathology
      among persons with AD.

PMID- 8295662
TI  - IVth Serling symposium on the biology of aging: a summary.

PMID- 8295663
TI  - The aging monkey: behavior and neurobiology current status and future trends.

PMID- 8295664
TI  - Neural circuitry underlying behavioral deficits in aging.

PMID- 8295665
TI  - Behavioral changes in aged rhesus monkeys.

PMID- 8295666
TI  - Neuropsychological and neurophysiological changes in healthy adult humans across
      the age range.

PMID- 8295667
TI  - Neuropsychological analysis of learning and memory in the aged nonhuman primate.

PMID- 8295668
TI  - Issues in the development of models for cognitive aging across primate and
      nonprimate species.

PMID- 8295669
TI  - The longitudinal assessment of recognition memory in aged rhesus monkeys.

PMID- 8295670
TI  - Age-related behavioral impairments: benefits of multiple measures of performance.

PMID- 8295671
TI  - Cognitive changes during normal aging in monkeys assessed with an automated test
      apparatus.

PMID- 8295672
TI  - Electrophysiological changes in hippocampus of aged rodents: predictions for
      functional change in aged primate.

PMID- 8295673
TI  - A perspective on behavioral studies in aged monkeys.

PMID- 8295674
TI  - Critical issues in the analysis of dendritic extent in aging humans, primates,
      and rodents.

PMID- 8295675
TI  - The stability of synaptic measures in cortex and hippocampus.

PMID- 8295676
TI  - The absence of significant neuronal loss from cerebral cortex with age.

PMID- 8295677
TI  - The relationship of cerebral cortical changes to nuclei in the brainstem.

PMID- 8295678
TI  - The relationship between tangle and plaque formation during healthy aging and
      mild dementia.

PMID- 8295679
TI  - Beta-protein fibrillogenesis and its impact on neuropil and microvessels.

PMID- 8295680
TI  - Comparative neuropathology of aged nonhuman primates.

PMID- 8295681
TI  - Comparing age-related changes in the basal forebrain and hippocampus of the
      rhesus monkey.

PMID- 8295682
TI  - Morphological analyses of the brains of behaviorally characterized aged nonhuman
      primates.

PMID- 8295683
TI  - The incidence of senile plaques and multiple infarction in aged macaque brain.

PMID- 8295684
TI  - Plaques in prefrontal cortex of aged, behaviorally-tested rhesus monkeys:
      incidence, distribution, and relationship to task performance.

PMID- 8295685
TI  - Purification and cloning of monkey proteases involved in the processing of the
      beta-amyloid precursor protein.

PMID- 8295686
TI  - Cellular dynamics of senile plaque formation and amyloid deposition in cerebral
      cortex: an ultrastructural study of aged nonhuman primates.

PMID- 8295687
TI  - Overview of neuropathology in aged monkeys.

PMID- 8295688
TI  - Longitudinal study of aging in monkeys: effects of diet restriction.

PMID- 8295689
TI  - Age-related changes in monkey and rodent neurochemistry.

PMID- 8295690
TI  - The aged memory-impaired rat: neurochemical features and possible relevance to
      primates and humans.

PMID- 8295691
TI  - Changes in cholinergic receptor subtypes in behaviorally-tested, aged monkeys.

PMID- 8295692
TI  - Age-related behavioral and neurochemical deficits: new data analytic strategies.

PMID- 8295693
TI  - Age-related behavioral and neurochemical deficits: the cholinergic system
      revisited.

PMID- 8295694
TI  - Do brain-behavior correlations hold across species?

PMID- 8295695
TI  - Limitations of morphological studies in human brain: opportunities for studies in
      nonhuman primates.

PMID- 8295696
TI  - General overview: past contributions and future opportunities using aged nonhuman
      primates.

PMID- 8295697
TI  - [The experiences of a large amount of steroid therapy for symptomatic vasospasm
      after subarachnoid hemorrhage: clinical analysis of 21 cases].
AB  - Among 48 cases of subarachnoid hemorrhage, 21 cases (43.8%) showed symptomatic
      vasospasm. We attempted treatment, using a large amount of steroid therapy for
      them in accord with our own protocol. In the 21 cases who received steroid
      therapy for symptomatic vasospasm, 18 cases (85.7%) showed improvement of their
      symptoms. This was especially evident in about 8 cases where the steroid effect
      was remarkable. There was a serious side effect, GI--tract bleeding, in one case.
      Although the effect of the steroid therapy was evident for slight or moderate
      spasm cases, 5 severe spasm cases responded poorly. We concluded that a large
      amount of steroid therapy was effective for slight or moderate symptomatic
      vasospasm cases, and that in severe ones possibly another therapy combined with
      steroid therapy would be necessary.

PMID- 8295698
TI  - [Neuropathological study of battered child syndrome: eight autopsy cases].
AB  - The term "battered-child syndrome" was coined by Kempe in 1962. The morphology of
      brain lesions in abused children is rarely reported in Japan. This
      clinicopathological entity in the central nervous system is characterized by
      retinal hemorrhages, subdural and subarachnoid hemorrhage. However, reports on
      microscopic findings of intracerebral lesion are fewer than those on macroscopic
      findings of scalp, skull and intracranial cavity. This study was performed on 8
      cases of battered children who were autopsied. They consisted of six female and
      two male infants. The age ranged from one week to four years old. The causes of
      the injuries were shaking in four cases, throwing in three cases, dropping in two
      cases and strangling in one case, mostly in combination. CT scans were examined
      for three cases. CT scan revealed acute cerebral swelling and acute subdural
      hematoma with interhemispheric blood clot in three cases and multiple low density
      area in one case. Evacuation of the subdural hematoma and external decompression
      was performed in one case. The survival period from injury to death was one day
      in four cases, and 2, 3, 9 and 41 days in the others. In the gross anatomical
      findings there are many excoriations and bruises of the face and scalp in five
      cases, widespread subcutaneous hematoma in all cases and skull fracture in only
      two cases. The brain weight was exceedingly heavier than normal brain weight by
      age in five cases. In the macroscopic findings, there were marked cerebral
      swelling and cerebral herniation in all cases, traumatic subarachnoid hemorrhage
      in six cases, and thin widespread acute subdural hematoma with interhemispheric
      clot in four cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295699
TI  - [Technical tactics to preserve cortical venous drainage in interhemispheric
      approach for anterior communicating artery aneurysms].
AB  - The interhemispheric approach has been selected for clipping of the anterior
      communicating artery aneurysm located high above the sphenoidal plate, and in a
      posterior direction. However, this approach is sometimes complicated with
      postoperative hemorrhagic infarction due to excess brain retraction combined with
      damages of the cortical bridging veins. We have devised a modification in this
      approach to eliminate these complications. Our newly devised methods include the
      following; 1) Small bifrontal craniotomy performed, 2) Continuous ventricular
      drainage performed to minimize the effect of compression by the spatula during
      resection of interhemispheric fissure, 3) Bifrontal dural incision made along the
      frontal skull base, 4) Mobilization of the major cortical vein in the operated
      field, if necessary, by resection of the overlying arachnoid membrane with or
      without sacrificing its small tributaries, 5) Gradual dissection of the olfactory
      nerves according to the process of operation. We analysed the incidence of
      operative complications in thirteen consecutive cases with this approach. Major
      frontal ascending veins were carefully preserved in all cases. None showed
      hemorrhagic infarction, regardless of the cortical venous drainage patterns. The
      degree of smell preserved in 10% of the examined 11 cases was more than
      unilateral. In conclusion, this method is useful for the elimination of
      perioperative complications even in the acute stage of subarachnoid hemorrhage.

PMID- 8295700
TI  - [Pharmacokinetics of plasma and cerebrospinal fluid cisplatin in patients with
      malignant glioma and metastatic brain tumor after selective intraarterial or
      intravenous and intracarotid administration of etoposide and cisplatin].
AB  - CSF and plasma platinum levels were examined in patients with malignant glioma
      after administration of etoposide and cisplatin each at doses of 60 mg/m2 by 60
      minute selective intraarterial infusion. These same factors were also examined in
      patients with metastatic brain tumors after administration of cisplatin at a dose
      of 60 or 100mg/m2 by 60-minute intracarotid or intravenous infusion. Plasma and
      CSF samples taken through an Ommaya reservoir placed in the lateral ventricle or
      postoperative cavity were analyzed for platinum content by atomic absorption
      spectroscopy. Plasma and CSF platinum levels were dose dependent. The overall
      plasma platinum curves were biphasic, with mean half-lives of 35 minutes and 56
      hrs. The mean peak total CSF concentration was 10.0% of the peak total plasma
      platinum and 20.2% of the peak free plasma platinum in patients with malignant
      glioma. In patients with a solid metastatic brain tumor, the mean peak total CSF
      concentration was 1.9% of the peak total plasma platinum and 4.0% of the peak
      free plasma platinum after i.v. infusion. After intracarotid infusion, the mean
      peak total CSF concentration was 3.4% of the peak total plasma platinum and 7.0%
      for the peak free plasma platinum. In patients with meningeal carcinomatosis, the
      mean peak CSF concentrations were 7.7% of the peak total plasma platinum and
      13.7% of the peak free plasma platinum. The free to total platinum ratio in
      plasma decreased quickly and that in CSF increased and was maintained at the high
      levels of 80% for two hours or more.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295701
TI  - [Management for subarachnoid hemorrhage with negative initial angiography].
AB  - Subarachnoid hemorrhage (SAH) is commonly caused by ruptured aneurysm or
      arteriovenous malformation which is detected by cerebral angiogram. However,
      since angiograms sometimes cannot show the origin of SAH, we review 12 cases
      (6.3% of total SAH) to assess the management of these cases. We divided the 12
      cases into three groups. Group A (occulted aneurysm group) consisted of six cases
      of which aneurysms were detected by repeated angiographies in four, and by
      surgical procedures in two. Group U (unknown etiology group) consisted of five
      cases. Their follow up periods varied from 7 months to 7 years 11 months, and all
      of them recovered well and had no episode of rebleeding. Group R (rebleeding
      group) consisted of one case which fatally re-bled on the second day. Group A
      tended to be Hunt and Hess grade 3, and Fisher group 3 or 4. In contrast, group U
      tended to be H and H grade 1 or 2, and Fisher group 2. However by their clinical
      and neuroradiological findings alone, it was not possible to distinguish the two
      groups certainly. This means that the patients whose initial angiography does not
      show the origin of bleeding must be cared for as an occult aneurysm case. Twice
      repeated angiograms should be programmed. In our cases the first was carried out
      on the seventh day in the hope that the reason for vasospasm of the parent artery
      might be shown to be a hidden aneurysm. The second was carried out sometime
      between the 14th and 21st day because of thrombolysis in the aneurysm, and
      because it was necessary to relieve vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295702
TI  - [Ossified epidural hematomas: report of two cases].
AB  - Two cases of ossified epidural hematomas were reported. Patients were nine and
      twelve year-old boys. Initially they were both followed up conservatively after
      injuries. Subsequently they were found on CT scan to have calcifications in the
      capsules of epidural hematomas which were found four months after injury in one
      case and twelve days after injury in the other. Both underwent craniotomy and
      histological ossification was found in the capsules of the hematomas. Epidural
      hematomas in children are known to ossify, and this condition may prevent natural
      absorption of epidural hematomas. Therefore, careful follow up of hematomas seems
      to be mandatory on conservative therapy of epidural hematomas in children.

PMID- 8295703
TI  - [A case of Hangman's fracture associated with vertebral arteriovenous fistula
      treated with trapping].
AB  - A case of a traumatic vertebral arteriovenous fistula associated with a hangman's
      fracture is reported. A 45-year-old male fell down about 2 meters and struck his
      parietooccipital region against the ground. Profuse nasal bleeding developed. He
      was transferred to a local hospital, where his respiration was ataxic and blood
      pressure was low. After intubation, he was transferred to our emergency
      department. Cervical x-p revealed fracture of C1, C2 and subluxation of C2 body.
      Because of uncontrollable nasal bleeding, the bilateral maxillary arteries were
      embolized with spongel. At this time, right vertebral angiograms demonstrated a
      vertebral arteriovenous fistula with an pseudoaneurysm located at C2 level. On
      the 13th hospital day, direct balloon occlusion of the fistula was attempted;
      this could not be achieved because the subclavian and vertebral arteries were
      tortuous and the balloon catheter could not be introduced to the level of the
      fistula in the vertebral artery. The patient was only observed until follow-up
      angiogram on the 24th hospital day revealed enlargement of the pseudoaneurysm. We
      performed trapping of both the proximal and distal ends of the involved vertebral
      artery; from C5 to C1. Postoperative course was uneventful, hangman's fracture
      was fixed with a Halo vest. Four months after operation, fistula and
      pseudoaneurysm were not opacified on angiogram. We believe that transvascular
      techniques are the treatment of choice for vertebral arteriovenous fistulas.
      However, as the next best thing, we can use trapping for the patient whose
      vessels are too tortuous to introduce the balloon catheter to the involved
      vessel.

PMID- 8295704
TI  - [Reduction cranioplasty for a case of intractable chronic subdural hematoma in
      infancy].
AB  - Although almost all infants suffering chronic subdural hematomas (CSDH) are
      successfully treated by established methods such as a subdural puncture, burr
      holes and shunting procedures, infantile CSDH with progressive craniocerebral
      disproportion requires a special therapeutical regimen. Clinical efforts such as
      reduction cranioplasty have been made as a treatment for these cases. This is a
      case report of a 9-month-old male infant with an intractable CSDH, bilateral and
      large, and subsequent brain atrophy caused by traumatic head injury. Excellent
      results were obtained by a modified reduction cranioplasty. In brief, the patient
      was supine-positioned with a 20-degree flexion of the head in an attempt to
      obtain a large operative field. Bicoronal skin incision was combined with an
      additional linear one on the midline (T-shaped incision). Bilateral
      frontoparietal craniotomy with periosteum was made to keep the midline bony
      bridge overlying the superior sagittal sinus (SSS). The resulting extensive dural
      opening allowed complete evacuation of the subdural hematoma. Thereafter, the
      anterior part, ca. 4cm in width, of the bony bridge was removed in order to make
      the remaining bone able to be manipulated and connected to the frontal bone.
      Prior to this stage, SSS close to the crista galli was ligated and cut with the
      falx to avoid postoperative kinking. The dura mater was sutured so as not to
      leave an excessive subdural space. The bone flaps were trimmed to complete a good
      shaped reconstruction. Finally, the excessive scalp was removed because the
      original scalp was too large for the reconstructed skull.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8295705
TI  - [Intracavernous internal carotid artery aneurysm associated with persistent
      trigeminal artery variant: case report].
AB  - The authors report a case of an intracavernous internal carotid artery aneurysm
      associated with a persistent trigeminal artery variant (PTAV). A 47-year-old
      woman developed a subarachnoid hemorrhage due to the rupture of aneurysm and
      underwent direct clipping operation. PTAV is basically an anomalous anastomosis
      between the internal carotid artery and the anterior inferior cerebellar artery.
      In this patient, the PTAV originated from the C4 portion of the right internal
      carotid artery and distributed in the territory of the hemispheric branch of the
      posterior inferior cerebellar artery. There have been only three reported cases
      of the internal carotid artery aneurysms arising from the crotch of PTAV. It is
      also unusual that rupture of such a small aneurysm in the cavernous sinus causes
      subarachnoid hemorrhage. Embryological development of PTAV and possible mechanism
      of subarachnoid hemorrhage from the intracavernous aneurysm are discussed.

PMID- 8295706
TI  - [Computer assisted neurosurgery based on individualized functional anatomy].

PMID- 8295707
TI  - [A case of malignant lymphoma in the skull base].
AB  - A case of malignant lymphoma located in the clivus, sella and cavernous sinus is
      reported. A 46-year-old female was hospitalized with a 3-week history of
      diplopia. Neurological examination showed left oculomotor, trochlear, abducens
      and hypoglossal nerve palsy. Improvement of cranial nerve palsy was achieved with
      the administration of prednisolone but it was only transient. Laboratory studies
      and endocrinological examination showed almost no abnormal findings. Skull x-ray
      film revealed a widely damaged base. MR studies showed a homogeneously enhanced
      mass lesion in the clivus, sella and bilateral cavernous sinus. Partial removal
      of the lesion was performed via the transsphenoidal route. The histopathological
      diagnosis of the mass was consistent with diffuse, medium sized cell, B-cell type
      malignant lymphoma. A postoperative systemic evaluation by tumor scan with 67Ga
      disclosed no abnormal uptake except in the skull base. Postoperatively, the
      patient was treated with radiation, a total of 50 Gy, followed by chemotherapy
      every 3 week consistent of cyclophosphamide, vincristine, pirarubicin, bleomycin,
      procarbazine and prednisolone. The cranial nerve symptoms disappeared during
      radiation therapy. The MR studies after three courses of chemotherapy revealed
      almost complete remission. The patient died of acute progression of pneumonia
      without any evidence of the recurrence of malignant lymphoma 10 months after the
      operation. Skull base involvement of malignant lymphoma is unusual. Five cases of
      malignant lymphoma invading the skull base have been reported since 1987. In most
      cases, the lesion originated from paranasal sinuses and was usually accompanied
      with intradural extensions. In the case we have reported there was no intradural
      invasion of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295708
TI  - [A multicentric glioma exhibiting three supratentorial lesions].
AB  - We reported a multicentric glioma having three separate lesions in the cerebrum.
      A 75-year old man was hospitalized with progressive disorientation. Computed
      tomography demonstrated two lesions in the left temporal lobe and the right
      frontal lobe. Magnetic resonance image disclosed one more lesion in the right
      occipital lobe. 2-staged operative procedures were performed for the left
      temporal and the right frontal tumors. It was histologically proven that one was
      glioblastoma and the other was anaplastic astrocytoma. The patient subsequently
      underwent radiotherapy and chemotherapy. Most multicentric gliomas are diagnosed
      in autopsy. Therefore it should be stressed that diagnosis is best made by biopsy
      or surgery. We discussed what therapy we should use for this fatal disease.

PMID- 8295709
TI  - [Hereditary hemorrhagic telangiectasia associated with cerebral arteriovenous
      fistula and multiple cerebral arteriovenous malformations: case report].
AB  - Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is an
      autosomal dominant disorder characterized by a triad of mucocutaneous and
      visceral telangiectasia, recurrent epistaxis and familial history. We reported a
      rare case of HHT associated with pulmonary and cerebral arteriovenous fistulae
      (AVF) and multiple cerebral arteriovenous malformations (AVM). The roles of
      multimodality therapies including artificial embolization, feeder clipping and
      stereotactic radiosurgery for these multiple cerebrovascular dysplasia in HHT
      were discussed. In particular the usefulness of radiosurgery to obliterate AVM
      was emphasized. It is especially useful for multiple AVM's associated with HHT. A
      7-year-old boy had presented himself at another hospital 2 years previously with
      cyanosis of the lips and fingers on exertion. He was diagnosed as having
      pulmonary AVG and underwent surgery. His mother had suffered from epistaxis in
      her adolescence, and was then highly suspected as having HHT. She underwent
      surgical removal of a left fronto-parietal AVM at the age of 16 years. The family
      history then prompted the patient to have a brain CT done, which eventually
      demonstrated an abnormal enhancing mass at the left frontal region. He was
      transferred to our service for further evaluation. Left carotid angiograms
      demonstrated an AVF supplied by a dilated anterior internal frontal artery of the
      anterior cerebral artery (ACA), draining directly into the vein of the corpus
      callosum with a large aneurysmal dilatation, and then draining further into the
      straight sinus via the vein of Galen. In addition, right carotid angiograms
      revealed three small AVM's fed by the median artery of the corpus callosum, and
      the middle internal frontal and paracentral arteries of the right ACA,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295710
TI  - Venlafaxine exhibits pre-clinical antidepressant activity in the resident
      intruder social interaction paradigm.
AB  - Venlafaxine, a novel 2-phenyl-2-(1-hydroxycycloalkyl) ethylamine, is a potent
      inhibitor of 5-hydroxytryptamine and noradrenaline reuptake and exhibits a
      profile of activity in pre-clinical in vitro biochemical studies predictive of
      antidepressant activity. The studies described here examined the effects of acute
      and chronic treatment with venlafaxine on the behaviour of resident rats
      confronted with an unfamiliar, non-treated, intruder conspecific. Ethological
      analysis of the social encounters revealed that acute, subcutaneous, treatment
      with venlafaxine, 20-180 mumol kg-1, induced a selective, dose-related, reduction
      in aggressive behaviour (ID50 = 24.87 mumol kg-1) concomitant with increased
      flight behaviour. In contrast, chronic treatment with venlafaxine, 20 mumol kg-1
      day-1, via subcutaneously-implanted osmotic mini-pumps, induced a marked
      elevation in aggressive behaviour concomitant with reduced flight behaviour.
      These diametrically opposite effects of acute and chronic venlafaxine treatment
      on the agonistic behaviour of resident rats are consistent with the behavioural
      effects of similar treatment regimes previously identified for a range of
      antidepressant drugs that differ widely in their acute pharmacology. These data
      strongly support the potential antidepressant activity of venlafaxine and are
      consistent with the results of recent clinical trials which demonstrate that
      venlafaxine exhibits significant antidepressant activity.

PMID- 8295711
TI  - Kindling to the benzodiazepine receptor inverse agonist, FG 7142: evidence for
      involvement of NMDA, but not non-NMDA, glutamatergic receptors.
AB  - Repeated administration of the beta-carboline FG 7142 to mice leads to the
      development of kindled convulsions. In order to investigate a role for
      glutamatergic mechanisms in the processes underlying FG 7142 kindling, the N
      methyl-D-aspartate (NMDA) antagonist, 2-amino-7-phosphono-heptanoic acid (AP7; 25
      nmol), was administered intracerebroventricularly (i.c.v.) daily before
      administration of FG 7142 (40 mg/kg, i.p.). Under these conditions, kindling to
      FG 7142 did not occur. Administration of two antagonists at non-NMDA excitatory
      amino acid receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and gamma-D
      glutamylaminomethylsulphonic acid (gamma-D-GAMS; both 25 nmol) did not prevent
      the development of seizures; these doses were, however, adequate and selective in
      protecting against seizures induced by respectively quisqualic and kainic acids
      given by i.c.v. The susceptibility of mice kindled with FG 7142 to seizures
      induced by NMDA, or kainate or quisqualate was similar in mice which had shown 5
      kindled seizures to that seen in drug-naive mice; mice which had shown 10 kindled
      seizures showed a decreased sensitivity to NMDA-induced convulsions (ED50 was
      increased from 0.24 to 0.31 nmol). No changes were seen in the convulsant
      thresholds of either NMDA or non-NMDA agonists. These observations suggest that
      although NMDA receptors appear to be involved in the processes underlying FG 7142
      kindling, such kindling is not necessarily associated with an increased
      sensitivity of glutamate receptors, and in animals which have convulsed, a
      decreased sensitivity to NMDA agonists occurs.

PMID- 8295712
TI  - DAMGO ([D-Ala2,NMePhe4,Gly-ol]enkephalin), but not DPLPE ([D-Pen2,L-
      Pen5]enkephalin), specifically inhibits methamphetamine-induced behavioral
      responses in the mouse.
AB  - The effects of intracerebroventricular (i.c.v.) injections of mu- and delta
      selective opioid agonists on the methamphetamine-induced behavioral alterations
      in the mouse were determined by using multi-dimensional behavioral analyses.
      Methamphetamine (1.0 mg/kg) produced a marked increase in linear locomotion,
      circling, rearing and grooming behavior. Although the mu-selective opioid agonist
      [D-Ala2,NMePhe4,Gly-ol]enkephalin (DAMGO) (0.003 and 0.01 microgram) itself did
      not significantly affect different behavioral responses, DAMGO (0.003 and/or 0.01
      microgram) antagonized the methamphetamine (1.0 mg/kg)-induced increase in
      behavioral responses such as linear locomotion, circling, rearing and grooming.
      Additionally, the effects of DAMGO (0.01 microgram) on the methamphetamine (1.0
      mg/kg)-induced behavioral responses were fully reversed by pretreatment with the
      mu-selective alkylating agent beta-funaltrexamine (beta-FNA) (5.0 micrograms). In
      contrast, the delta-selective opioid agonist [D-Pen2,L-Pen5]enkephalin (DPLPE)
      (0.3 or 1.0 microgram) had no marked effects on the methamphetamine (1.0 mg/kg)
      induced behavioral responses. These results suggest that the stimulation of mu
      but not delta opioid receptors plays an inhibitory role in the methamphetamine
      induced behavioral responses.

PMID- 8295713
TI  - The effect of dizocilpine and enadoline on immediate early gene expression in the
      gerbil global ischaemia model.
AB  - Increases in mRNA levels for c-fos, c-jun, junB, hsp70 and NGFI-A were observed
      in the dentate gyrus of the hippocampus following 7 min ischaemia in the
      Mongolian gerbil. The response was rapid and transient (30 min to 4 hr) for NGFI
      A, junB and c-fos mRNA. In contrast c-jun mRNA remained increased for several
      hours. Hsp70 increased in the dentate gyrus 1 hr after the insult, returned to
      control values at 4 hr and showed a secondary increase at 24 hr. At 24 hr
      increased hsp70 mRNA was observed in other regions of the CNS, i.e. CA1, CA2, CA3
      and cortex. The non-competitive NMDA receptor antagonist, dizocilpine, attenuated
      the increases in IEG expression and was neuroprotective. In contrast the kappa
      opiate receptor agonist, enadoline, protected the CA1 neurones from degeneration
      but did not inhibit the increased levels of IEG mRNA. Increases in hsp70 mRNA
      were reduced to baseline by both enadoline and dizocilpine. These results suggest
      that inhibition of IEG expression is not a prerequisite for neuroprotection.
      However, hsp70 was predictive of neuronal protection and may be a useful assay in
      this and related models.

PMID- 8295714
TI  - Effects of adenosine and cadmium on presynaptic fiber spikes in the CA1 region of
      rat hippocampus in vitro.
AB  - Adenosine was found to decrease the amplitude of presynaptic fiber spikes
      recorded in stratum radiatum of the CA1 region of the hippocampus following
      stimulation of the Schaffer collateral and commissural afferents. The presynaptic
      fiber spike reflects currents activated in the presynaptic fibers and nerve
      terminals of this projection. However, the effect of adenosine was largely the
      result of: (a) temporal overlap between the presynaptic fiber spike and the field
      EPSP response and (b) an indirect effect most likely related to the
      hyperpolarization of CA3 neurons giving rise to the Schaffer collateral fibers.
      When the CA3 region was separated by a knife cut from the CA1 region and the
      field EPSP blocked with 6,7-dinitroquinoxaline-2,3-dione, the effect of adenosine
      was markedly reduced, but was still significant (4.4 +/- 1.4% reduction in the
      amplitude of the presynaptic fiber spike). However, this action was not mimicked
      by the Ca2+ channel antagonist cadmium, suggesting that it did not reflect an
      inhibition of Ca2+ currents by adenosine. This effect was not observed in the
      presence of the K+ channel antagonists Ba2+ or diaminopyridine. These results
      suggest that adenosine may have a small hyperpolarizing effect on the presynaptic
      nerve terminals, but this is unlikely to be the mechanism by which adenosine
      modulates transmission in this brain region.

PMID- 8295715
TI  - CGP 55845A: a potent antagonist of GABAB receptors in the CA1 region of rat
      hippocampus.
AB  - The new GABAB receptor antagonist CGP 55845A was tested on pre- and post-synaptic
      GABAB receptors in the hippocampus. CGP 55845A (1 microM) blocked (-)-baclofen (5
      10 microM)-induced postsynaptic hyperpolarization and depression of evoked IPSPs
      and EPSPs. It also blocked three physiological consequences of GABAB receptor
      activation: the late IPSP, paired-pulse depression of IPSCs, and heterosynaptic
      depression of EPSPs. Therefore, CGP 55845A is an antagonist at pre- and post
      synaptic GABAB receptors in the hippocampus and is approximately three orders of
      magnitude more potent than previously described GABAB receptor antagonists.

PMID- 8295716
TI  - Role of the locus coeruleus in the noradrenergic response to a systemic
      administration of nicotine.
AB  - Experiments were conducted using in vivo microdialysis to ascertain the role of
      nicotinic receptors in the terminal, or the cell body area, in the hippocampal
      noradrenaline response provoked by a systemic administration of nicotine. These
      experiments combined systemic administration of nicotine with local
      administration of antagonists into the hippocampus via the microdialysis probe,
      or close to the LC via a cannula, while continuously monitoring extracellular
      levels of NA in the hippocampus. Systemic administration of nicotine (0.4 mg/kg,
      s.c.) produced a rapid and prolonged increase in extracellular levels of
      noradrenaline in the hippocampus of conscious animals, reaching a maximum in the
      first 10 min sample. In anaesthetised animals the maximum occurred 20 min after
      administration, but the subsequent response profile was similar. In both
      anaesthetised and freely moving animals nicotine increased extracellular levels
      of dihydroxyphenylacetic acid and homovanillic acid in the hippocampus, but
      failed to alter levels of dopamine or 5-hydroxyindoleacetic acid. In
      anaesthetised animals intrahippocampal administration of nicotine (250 microM
      over 10 min via the dialysis probe) significantly increased extracellular levels
      of noradrenaline; the response was shortlasting, being evident only in the 10 min
      sample during exposure to the drug. Local administration of nicotine failed to
      alter extracellular levels of any other amine or metabolite measured.
      Mecamylamine (25 microM), a nicotinic channel blocker, administered
      intrahippocampally 10 min prior to an intrahippocampal administration of nicotine
      completely blocked the increase in noradrenaline. However, intrahippocampal
      administration of mecamylamine (25 microM) for 10 min, or for the duration of
      recording, failed to antagonise the effect of a systemic administration of
      nicotine (0.4 mg/kg, s.c.) on extracellular levels of noradrenaline,
      dihydroxyphenylacetic acid or homovanillic acid. In contrast administration of
      mecamylamine (50 microM) close to the locus coeruleus abolished the increase in
      noradrenaline levels in the ipsilateral hippocampus following a systemic
      administration of nicotine (0.4 mg/kg, s.c.), while trimethaphan (50 microM), a
      nicotine receptor antagonist, significantly reduced the response. Administration
      of mecamylamine also attenuated increases in dihydroxyphenylacetic acid and
      homovanillic acid, suggesting that the response of these metabolites may be
      associated with the functional metabolism of noradrenergic neurones. Locus
      coeruleus administration of kynurenic acid (1 mM), a non-specific excitatory
      amino acid antagonist, was without effect. Finally, application of nicotine (50
      microM) close to the locus coeruleus significantly increased extracellular levels
      of noradrenaline in the ipsilateral hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8295717
TI  - Characterization and solubilization of the sulphonylurea receptor in rat brain.
AB  - The binding characteristics of the sulphonylurea receptor were investigated using
      rat brain microsomes. Scatchard plots for binding of [3H]glibenclamide, a potent
      sulphonylurea which inhibits the ATP-sensitive K-channel, suggested the presence
      of both high and low affinity binding sites with Kd of 0.58 and 17 nM, and beta
      max of 123 and 392 fmol/mg protein, respectively. When brain microsomes were
      solubilized with CHAPS, high affinity sites were retained with Kd and beta max of
      1.2 nM and 42.1 fmol/mg protein, respectively, whereas the low affinity sites
      disappeared. The specific binding was displaced by non-labelled glibenclamide,
      meglitinide, and tolbutamide with IC50 at 5 nM, 25 microM and 130 microM,
      respectively. ATP and GTP inhibited [3H]glibenclamide binding in a Mg-dependent
      manner whereas the inhibition by ADP and GDP was Mg-independent [3H]Glibenclamide
      binding to the solubilized receptor was similarly inhibited by those nucleotides.
      Diazoxide inhibited [3H]glibenclamide binding in the presence of MgATP, but after
      CHAPS-solubilization diazoxide failed to inhibit [3H]glibenclamide binding even
      with MgATP. These findings suggest the brain sulphonylurea receptor has similar
      features to the beta-cell receptor. However, inhibition of the binding by
      nucleotides is not identical, possibly reflecting differences in the nucleotide
      binding subunit.

PMID- 8295718
TI  - Increase in serotonin levels in the dog ileum and blood by cisplatin as measured
      by microdialysis.
AB  - Involvement of ileal and circulating serotonin (5-HT) levels in cisplatin-induced
      emesis was examined using a microdialysis technique and an extraction method in
      dogs. The 5-HT levels in the ileal dialysate were increased to 232-294% of the
      basal level from 100 to 180 min after cisplatin administration (3 mg/kg, i.v.)
      and had returned to the basal level 280 min after dosing. The 5-HT levels in the
      blood dialysate were increased to 424-2165% from 140 to 180 min after dosing. The
      concentrations of 5-HT determined by HPLC following extraction were increased to
      271% in the ileal mucosa and to 478% in plasma 3 hr after dosing. In
      immunohistochemistry, the number of 5-HT-immunoreactive cells was increased to
      166% in the ileal mucosa following cisplatin treatment. These results strongly
      suggest that increases in the release and synthesis of 5-HT in the gut, probably
      in the enterochromaffin cells, are intimately involved in cisplatin-induced
      emesis.

PMID- 8295719
TI  - Lack of expression of serotonin receptor subtype -1a, 1c, and -2 mRNAs in
      gonadotropin-releasing hormone producing neurons of the rat.
AB  - Serotonin is one of the neurotransmitters which participates in the regulation of
      gonadotropin-releasing hormone (GnRH) release from the hypothalamus. In order to
      test the hypothesis that serotonin acts directly on the GnRH neurons, dual in
      situ hybridization with 35S-labeled cRNA probes encoding for the serotonin
      receptor subtypes-1a, -1c, or -2 together with digoxigenin-labeled GnRH cRNA
      probes was applied to histological sections of the septum-diagonal band and
      preoptic area. The results of these studies show that many neurons in these brain
      regions contain the various serotonin receptor mRNAs, however, no cells were
      detected that contain both GnRH mRNA and serotonin receptor mRNAs. It is
      therefore suggested that the effects of serotonin on GnRH release are not
      mediated by direct actions of the neurotransmitter through serotonin-1a, -1c or 
      2 receptors on GnRH neurons but instead through other, yet unidentified serotonin
      receptor subtypes or through non-serotoninergic intermediary neurons.

PMID- 8295720
TI  - [125I]iodomelatonin binding sites in the chicken spinal cord: binding
      characteristics and diurnal variation.
AB  - [125I]Iodomelatonin ([125I]MEL) binding in chicken spinal cords was
      characterized. The specific binding of [125I]MEL to the membrane preparation of
      spinal cord was rapid, stable, saturable, reversible, specific and of high
      affinity. Scatchard analysis of the specific binding data indicated an
      equilibrium dissociation constant (Kd) of 30.7 +/- 3.43 pM and a maximum number
      of binding sites (Bmax) of 1.69 +/- 0.14 fmol/mg protein in spinal cords
      collected at mid-light. The diurnal variation study showed that the Bmax was 32%
      higher (P < 0.05) at mid-light compared to mid-dark. The pharmacological
      characteristics demonstrated that [125I]MEL binding sites was highly specific for
      melatonin. Our results suggest that melatonin may exert a direct action on the
      spinal cord.

PMID- 8295721
TI  - Location and axonal projection of early-onset decrementing expiratory neurons in
      the cat.
AB  - The location and axonal projection of early-onset decrementing expiratory (eE
      DEC) neurons were studied in Nembutal-anesthetized, paralyzed, and artificially
      ventilated cats. The eE-DEC neurons started firing around the peak of phrenic
      activity and attained maximum firing at the transition from inspiration to
      expiration. The eE-DEC neurons were distributed in the dorsomedial border of the
      dense assembly of respiratory neurons of the ventral respiratory group and the
      Botzinger complex. Antidromic microstimulation showed that the eE-DEC neurons
      projected mainly to the ipsilateral reticular formation medial and dorsal to the
      nucleus ambiguus at the level of the obex but rarely to the medullary respiration
      related areas. Participation of these eE-DEC neurons in the inspiratory off
      switch may not be possible.

PMID- 8295722
TI  - Extinction of emotional learning: contribution of medial prefrontal cortex.
AB  - Stimuli associated with painful or otherwise unpleasant events acquire aversive
      emotional properties in animals and humans. Subsequent presentation of the
      stimulus alone (in the absence of the unpleasant event) leads to the eventual
      extinction of the aversive reaction. Although the neural basis of emotional
      learning has been studied extensively, considerably less is known about the
      neural basis of emotional extinction. In the present study, we show that the
      medial prefrontal cortex plays an important role in the regulation of fear
      extinction in rats, a finding that may help elucidate the mechanisms and,
      possibly, the treatment of disorders of uncontrolled fear, such as anxiety,
      phobic, panic and posttraumatic stress disorders in humans.

PMID- 8295723
TI  - Upregulation of A1 adenosine receptors in human temporal lobe epilepsy: a
      quantitative autoradiographic study.
AB  - A significant increase of A1 adenosine receptor binding (48% increase of mean)
      was detected in human neocortex obtained from patients suffering from temporal
      lobe epilepsy as compared to control neocortex from non-epileptic patients. Such
      increase was equally distributed in the six cortical layers and reached similar
      levels in each of the five specimens tested independently of age, sex and
      pharmacological treatment of the patient. Since adenosine exerts a depressant
      effect on neocortical neurons in slices obtained from epileptic patients, this
      upregulation of A1 receptor binding may constitute a protective mechanism against
      subsequent seizures, which is exerted by elevating the depressant response of the
      brain to endogenous adenosine.

PMID- 8295724
TI  - Regulation of glial fibrillary acidic protein in serum-free mouse embryo (SFME)
      cells by leukemia inhibitory factor and related peptides.
AB  - The serum-free mouse embryo (SFME) cell line, derived in serum-free medium from
      16-day-old mouse embryos, exhibits unique properties. SFME cells grow
      indefinitely in culture without senescence, require epidermal growth factor (EGF)
      or fibroblast growth factor (FGF) for survival and are growth-inhibited by serum.
      The cell line expresses glial fibrillary acidic protein (GFAP) in response to
      transforming growth factor beta or serum and cells with similar properties can be
      isolated directly from brain. Culture of SFME cells with leukemia inhibitory
      factor (LIF), a peptide implicated in neural tissue development, also resulted in
      expression of GFAP. Other peptides that share signal transduction mechanisms with
      LIF--ciliary neurotropic factor, oncostatin M and interleukin-6--also caused
      expression of GFAP in these cells. These effects were inhibited by concentrations
      of EGF or FGF that promoted rapid cell growth.

PMID- 8295725
TI  - Seizure-like activity disrupts LTP in vitro.
AB  - Amnesia is one of the most common consequences of seizures. We modelled this
      phenomenon in the in vitro hippocampal slice preparation by examining effects of
      seizure-like activity on long-term potentiation (LTP). LTP is an expression of
      neuronal plasticity which has been correlated with learning. Electrographic
      seizures (EGSs) were induced in area CA1 by electrical stimulation of CA3. Trains
      of tetanic stimuli were then immediately delivered to the Schaffer collateral-CA1
      pathway in order to induce LTP. The subsequent LTP in these test slices was
      significantly lower in magnitude compared to LTP in control slices (with no
      EGSs). LTP could be successfully induced in test slices 1 h after the EGS. EGSs
      alone produced no long-lasting effect on baseline responses. These results
      indicate that the hippocampal slice preparation may serve as a model system in
      which to study the mechanisms by which seizures can disrupt neuronal plasticity.

PMID- 8295726
TI  - Age-related change in the proportion of amyloid precursor protein mRNAs in the
      gray matter of cerebral cortex.
AB  - Alternative splicing of a transcript of amyloid precursor protein (APP) gene
      generates at least three types of mRNA coding for APP770, APP751, and APP695; the
      former two harbor, while the latter one lacks a Kunitz-type serine protease
      inhibitor (KPI). We compared, by using the RNase protection technique, APP mRNAs
      expression between gray and white matters in the frontal lobe, with special
      reference to Alzheimer's disease (AD) and aging. The proportions (y) of APP770
      plus APP751 mRNAs in the white matter were nearly twice as much as those in the
      gray matter, both in control (non-AD) and AD brains; the difference between the
      two matters was statistically significant. Furthermore, in the gray matter of
      control, there was a positive correlation (y = 1.07 x-57.1, r = 0.899) between
      the age (x) and the proportion (y), but not in the white matter where the
      proportion varied markedly among individuals. In AD brains, no significant
      correlation was found in either of the two matters. These results indicated that
      the APP mRNAs proportion in the gray matter may serve as a molecular index of the
      brain aging in non-AD persons.

PMID- 8295727
TI  - Tetrahydroaminoacridine increases m3-, but not m2-, muscarinic acetylcholine
      receptor mRNA levels in differentiating cerebellar granule cells.
AB  - We used Northern blot hybridization to determine whether 9-amino-1,2,3,4
      tetrahydroacridine (THA), a potential antidementia drug, selectively altered the
      levels of muscarinic acetylcholine receptor (mAChR) mRNA in differentiating
      cerebellar granule cells. Granule cells were cultured for 8 days in media
      containing 15 mM K+, 25 mM K+ or 15 mM K+ plus 30 microM THA. High K+ markedly
      increased the levels of m2- and m3-mAChR mRNA in the surviving cells. In
      contrast, THA increased the levels of m3-mAChR mRNA, but had little or no effect
      on m2-mAChR mRNA levels. These results suggest that THA selectively up-regulates
      the synthesis of m3-mAChR mRNA.

PMID- 8295728
TI  - Neural correlates of memory for odor detection conditioning in adult rats.
AB  - Adult male Wistar rats were trained in a simple odor detection task, with
      peppermint odor serving as either an S+, S- or as a randomly presented odor.
      Twenty-four hours after the last training session, rats were injected with [14C]2
      deoxyglucose and exposed to the odor. Mean relative 2-deoxyglucose uptake to the
      odor was enhanced in the pars dorsalis of the anterior olfactory nucleus of S+
      and S- trained rats compared to controls. In contrast, no differences in uptake
      were detected in either odor-specific focal regions of the olfactory bulb
      glomerular layer, the pyriform cortex, or the hippocampus.

PMID- 8295729
TI  - Interleukin-1 alpha in blood has direct access to cortical brain cells.
AB  - Interleukin-1 alpha (IL-1 alpha), an immunoregulatory protein secreted by the
      peripheral immune system, affects the central nervous system (CNS). IL-1 alpha
      could directly enter the parenchyma of the brain in intact form to alter brain
      function, or it could be blocked or sequestered by the capillary bed comprising
      the blood-brain barrier (BBB) that normally retards entry of circulating proteins
      to the brain and cerebrospinal fluid (CSF). We show here by use of the selective
      interleukin receptor antagonist (IL-1ra), capillary depletion method, high
      performance liquid chromatography (HPLC) and saturation with unlabeled IL-1 alpha
      that radioactively labeled IL-1 alpha injected iv directly enters the CNS in
      intact form. This also occurs in the brain cortex, an area devoid of
      circumventricular organs (CVOs), and in the CSF, an area devoid of capillaries.
      Capillaries can also sequester IL-1 alpha in a saturable manner, suggesting that
      they may be the site for the carrier-mediated entry of IL-1 alpha into the CNS.
      Thus, the results show that circulating IL-1 alpha has direct access to cortical
      brain cells behind the BBB through a saturable transport system that provides a
      major pathway by which the brain and immune system interact.

PMID- 8295730
TI  - Evidence of a direct projection of the vomeronasal organ to the medial preoptic
      nucleus and hypothalamus.
AB  - In rodents the vomeronasal system plays an important role in modulating the
      hypothalamic control of gonadotropin secretion. It is accepted that the
      anatomical pathways by which the vomeronasal organ influences the neuroendocrine
      aspects of the reproductive behavior involves a polysynaptic system, including
      the accessory olfactory bulb, the 'vomeronasal amygdala', the bed nucleus of the
      stria terminalis and medial preoptic and ventromedial hypothalamic nuclei. We
      found that 72 h after unilateral transection of the vomeronasal nerves of an
      ipsilateral orthograde degeneration is seen in the neuropil of the medial
      preoptic, ventromedial, and arcuate hypothalamic nuclei. This represents an
      anatomical evidence of a monosynaptic link between the vomeronasal
      neuroepithelium and the medial preoptic nucleus, and hypothalamus.

PMID- 8295731
TI  - Uptake of L-lactate by cultured rat brain neurons.
AB  - The uptake of L-lactate was investigated in neuronal primary cultures derived
      from embryonic rat brain with a radioactive tracer method. After preincubation of
      the cells in glucose-free buffer for 30 min, uptake increased with time for at
      least 10 min. A saturable component of uptake was found with half-maximal uptake
      at 10 mM lactate. This saturable component was abolished in the presence of 10 mM
      alpha-cyano-4-hydroxcinnamic acid. In addition, a non-saturable component
      dominated the uptake at high concentrations of lactate. Uptake was accelerated
      with decreasing pH, and was inhibited considerably by pyruvate. It is concluded
      that neurons are endowed with a lactate transport system which resembles in its
      properties the monocarboxylate carrier of peripheral tissues.

PMID- 8295732
TI  - Cocaine enhancement of the action of 5-hydroxytryptamine in rat cingulate cortex
      in vitro.
AB  - Intracellular recordings were made in vitro from pyramidal neurons in layer V of
      the anterior cingulate cortex of the rat. 5-Hydroxytryptamine (5-HT) reduced the
      amplitude of the excitatory postsynaptic potential; receptor-selective agonists
      and antagonists indicated that this resulted from activation of the 5-HT1B
      receptor. The action of 5-HT was enhanced by cocaine (300 nM-3 microM); 1 microM
      cocaine increased sensitivity to 5-HT about 10-fold. The results suggest that
      cocaine is similarly effective to potentiate the action of 5-HT in the prefrontal
      cortex as in other brain regions. This may contribute to its overall in vivo
      effects.

PMID- 8295733
TI  - Immunohistochemical localization of a metabotropic glutamate receptor, mGluR5, in
      the rat brain.
AB  - A trpE-fusion protein containing a C-terminal sequence of a rat metabotropic
      glutamate receptor, mGluR5, was used to produce an antibody. On immunoblot, the
      antibody specifically reacted with mGluR5 expressed in mammalian cells and rat
      brain. Immunohistochemical analysis revealed intense mGluR5-like immunoreactivity
      (LI) in the olfactory bulb, anterior olfactory nuclei, olfactory tubercle,
      cerebral cortex, hippocampus, lateral septum, striatum, nucleus accumbens,
      inferior colliculus, and spinal trigeminal nuclei. The distribution pattern of
      mGluR5-LI corresponds very well with that of mGluR5 mRNA. Electron microscope
      analysis of the striatum revealed dense accumulation of immunoreaction products
      in dendrites which were often provided with asymmetrical synapses. These results
      suggest that mGluR5 is predominantly located in postsynaptic elements.

PMID- 8295734
TI  - Autoradiographic evidence for a bradykinin/angiotensin II receptor-receptor
      interaction in the rat brain.
AB  - Using angiotensin II (ANG II) to compete with (3-[125I]iodotyrosyl-4, Sar1,
      Ile8)ANG-II ([125I]Sar1, Ile8)ANG II) for its binding sites in the nucleus of the
      solitary tract (nTS) and the paraventricular hypothalamic nucleus (PV) bradykinin
      (10 nM) reduced the IC50 value (48 nM) of ANG II, an action blocked by the
      bradykinin B2 antagonist HOE-140 (100 nM). In contrast, when analysing the high
      affinity site (Kd 3.1 nM) for [125I]ANG II in the nTS bradykinin (10 nM)
      increased the Kd value. Thus, a central bradykinin/ANG II receptor interaction
      may exist involving a differential regulation of the high- and low-affinity ANG
      II receptors in the nTS. This regulation by bradykinin of angiotensin receptors
      in the nTS may help to explain the central vasopressor effect of bradykinin.

PMID- 8295735
TI  - Effects of physostigmine on local cerebral glucose utilization in the central
      components of the rat visual system.
AB  - The effects of intravenous administration of physostigmine at doses of 0.03,
      0.095, or 0.3 mg/kg on local cerebral glucose utilization (LCGU) were determined
      in 3 structures of the visual system of the rat brain by means of the
      quantitative 2-[14C]deoxyglucose method. LCGU was increased in the superior
      colliculus (superficial gray layer), but unchanged in the visual cortex and the
      lateral geniculate body. To determine whether the observed effect of
      physostigmine on the superior colliculus depended on input from the retina, the
      highest dose of physostigmine was administered to rats which had previously been
      enucleated bilaterally. Enucleation decreased LCGU in the superior colliculus of
      the animals not treated with physostigmine and blocked the effect of
      physostigmine on LCGU. The effect of physostigmine in the superior colliculus
      appears, therefore, to depend on input from the retina.

PMID- 8295736
TI  - Cholinergic amacrine cells of the rat retina express the delta-subunit of the
      GABAA-receptor.
AB  - Antibodies directed against the delta-subunit of the GABAA-receptor were applied
      to cryostat sections of rat retinae. Two narrow bands of the inner plexiform
      layer were strongly immunoreactive. Some cell bodies in both the amacrine- and
      ganglion-cell layer were weakly immunoreactive. The position of the labelled
      bands and the distribution of the cell bodies was strongly reminiscent of the
      cholinergic amacrine cells. In order to show directly that cholinergic amacrine
      cells express the delta-subunit of the GABAA-receptor, double immunofluorescence
      with an antibody against choline acetyltransferase (ChAT) and with antibodies
      against the delta-subunit was performed on the same cryostat sections. This
      showed the labelled cells to be cholinergic amacrine cells.

PMID- 8295737
TI  - Myenteric neuron number after acute and chronic denervation of the proximal
      jejunum induced by benzalkonium chloride.
AB  - The effects of benzalkonium chloride (BAC) on the number of myenteric neurons
      after acute (until 10 days after BAC application) and chronic (30 and 60 days
      after BAC application) denervation of the proximal jejunum were determined in
      rats. There was a significant reduction in the number of myenteric neurons of all
      segments treated with BAC. The extent of denervation varied with time, and it was
      reduced in the denervated segments of the chronic group in comparison with the
      acute group. This may be due to the neuroplasticity phenomenon appearing during
      the chronic phase.

PMID- 8295738
TI  - Peripheral peptide YY induces c-fos-like immunoreactivity in the rat brain.
AB  - The influence of peripheral injection of peptide YY (PYY) on neuronal activity in
      the rat brain was examined by immunohistochemical detection of c-fos protein.
      Numerous c-fos-immunoreactive nuclei were found in the area postrema, nucleus
      tractus solitarius (commissural and medial subnuclei), central amygdala and
      thalamus (periventricular and medial) of rats injected i.p. with PYY at a dose of
      300 micrograms/kg. c-fos-like immunoreactivity was found to be less when lower
      doses of PYY (50-200 micrograms/kg, i.p.) were injected. Either no or few cells
      were detected after i.p. injection of the vehicle alone. These data provide
      anatomical support for the centrally mediated actions of peripheral PYY on gut
      function.

PMID- 8295739
TI  - Platelet of Alzheimer patients: increased counts and subnormal uptake and
      accumulation of [14C]5-hydroxytryptamine.
AB  - Platelets are the main source of 5-hydroxytryptamine (5-HT) and amyloid precursor
      protein (APP) found in plasma. We studied a possible correlation between platelet
      markers and the clinical diagnosis of Alzheimer disease (AD). Our results
      indicate that in AD patients: (a) platelets are elevated, (b) their ability to
      accumulate 5-HT decreases and, (c) the kinetic parameters of 5-HT uptake are
      altered (decreased Km and Vmax), compared to non-demented healthy individuals. An
      aged Down syndrome patient presents even more deviant alterations. Our findings
      supports the idea that platelets may provide a systemic marker of AD, and
      eventually be useful for the clinical diagnosis of the disease.

PMID- 8295740
TI  - Xenogeneic dopaminergic grafts reverse behavioral deficits induced by 6-OHDA in
      rodents: effect of 15-deoxyspergualin treatment.
AB  - Foetal rat mesencephalic dopamine-containing tissue was transplanted into the
      lateral ventricle of mice previously subjected to a 6-OHDA lesion of dopaminergic
      nerve terminals in the corpus striatum. The graft recipients were
      immunosuppressed by subcutaneous injections of 15-deoxyspergualin (DSG). Four
      weeks postgrafting, all DSG-treated mice showed partial or complete functional
      compensation in amphetamine-induced motor asymmetry. The immunohistochemical
      staining of tyrosine hydroxylase (TH) revealed large numbers of surviving
      dopamine neurons and abundant fibers in the grafted animals. In contrast, all
      grafts in non-DSG-treated animals were rejected and functional compensation was
      lacking. It is concluded that DSG treatment promotes xenogeneic intracerebral
      graft survival, recovery of function and reduce the histological sign of
      rejection.

PMID- 8295741
TI  - Down-regulation of NMDA receptor activity by NMDA.
AB  - Rat cerebellar granule cells were cultured in a medium containing 25 mM KCl. The
      presence of NMDA during culture caused strong down-regulation of 45Ca uptake
      through the NMDA receptor channel. The process affected neither the viability nor
      the protein content of the cells. The developmental program of NMDA receptor
      activity was resumed after removal of NMDA from the culture medium, dependent
      apparently on protein synthesis. The down-regulation also rendered the neurons
      resistant to NMDA toxicity. It permitted replenishment of the culture with fresh
      medium, which is extremely toxic for cells cultured in absence of NMDA. Such down
      regulation might perhaps play a role in adjusting the activity of post synaptic
      NMDA receptors, following synaptogenesis.

PMID- 8295743
TI  - NADPH-diaphorase and NANC relaxations are correlated in the sheep urinary tract.
AB  - The present investigation was performed with the purpose of revealing by
      histochemical examination of NADPH-diaphorase activity and electrical field
      stimulation (EFS) of isolated preparations in vitro, whether a nitrergic
      innervation is present in the lower urinary tract of the sheep. NADPH-diaphorase
      positive fibers were found in the trigone and urethra, but not in detrusor and
      ureter. EFS elicited L-nitroarginine-sensitive relaxations of precontracted
      preparations from the trigone and urethra while it did not relax detrusor and
      ureteral preparations. The present results show a direct regional correlation
      between the NADPH-diaphorase activity and EFS-induced relaxations, and suggest
      the presence of an inhibitory nitrergic innervation, which might be of importance
      for relaxation of the bladder neck and urethra during voiding.

PMID- 8295742
TI  - Increased [35S]glutathione binding sites in spinal cords from patients with
      sporadic amyotrophic lateral sclerosis.
AB  - Recent observations have suggested abnormalities in the gene for superoxide
      dismutase (SOD1) in patients with the familial form of amyotrophic lateral
      sclerosis (ALS). As SOD activity has secondary effects on glutathione (GSH), we
      have evaluated [35S]GSH binding in spinal cord sections from patients who died
      with sporadic ALS and control subjects. [35S]GSH binding sites were present in
      the grey matter of spinal cords in both the dorsal and ventral horns. ALS
      patients showed significantly increased [35S]GSH binding (+16%) in the dorsal and
      ventral grey horns compared to controls. Scatchard analysis of saturation binding
      data revealed that increased [35S]GSH binding was due to changes in the number
      rather than the affinity of GSH binding sites. These findings add support to a
      role for GSH in the mechanism loading to the pathogenesis of sporadic ALS.

PMID- 8295744
TI  - Marine natural products.

PMID- 8295745
TI  - Sex specific birthweight percentiles by gestational age for New Zealand.
AB  - AIM: To produce sex specific percentiles by gestational age for New Zealand
      infants. METHODS: Gestational age (completed weeks) and birthweight (10 g
      multiples) was obtained for all births in New Zealand in 1990 and 1991. Outliers
      were identified and removed, the data was normalised at each gestational age and
      percentiles produced. RESULTS: The percentile charts were produced for
      gestational ages 24 to 44 weeks by sex of infant. There was an approximate
      difference of 100 g between male and female birthweight at all gestational ages.
      DISCUSSION: These are the first national birthweight percentile charts for New
      Zealand. As they may vary over time we recommend they be updated every 5 years.

PMID- 8295746
TI  - Infant home apnoea monitors in Christchurch: an audit.
AB  - AIM: To audit parental perception of the apnoea monitor service given to neonatal
      graduates and infants surviving an apparent life threatening event in
      Christchurch. METHODS: Seventy-five of 103 sets of parents (74%), who had
      monitored their infants, between November 1990 and November 1992, were
      interviewed using a structured telephone questionnaire (apparent life threatening
      event (ALTE) n = 44, significant recurrent apnoea (NNU) n = 31. RESULTS: Anxiety
      present in most parents (83%) was relieved by monitoring (89%). Parents (97%)
      were satisfied with the instruction in monitor use. Eighty-nine percent had good
      contact with the technician, 73% called her to solve a problem. Most parents
      (84%) thought that initial instruction in cardiopulmonary resuscitation (CPR) was
      adequate. Sixty-eight percent would have liked a refresher course which only 7%
      of NNU and 22% of ALTE parents received. Sixty percent of parents had at least
      one significant alarm. Nine percent performed CPR to abort an apnoea. Ten percent
      of parents would have liked to monitor their child longer. CONCLUSIONS: Apnoea
      monitoring allays parental anxiety and may save the lives of a few infants. A
      technician is essential to coordinate all aspects of the service. Improvements
      could be made to instruction for cardiopulmonary resuscitation.

PMID- 8295747
TI  - Traditional health practices in a modern Pacific: a dilemma or blessing?

PMID- 8295748
TI  - Methadone in general practice.

PMID- 8295749
TI  - Cytomegalovirus disease in transplant recipients.

PMID- 8295750
TI  - Lesion diagnosis clinics/pigmented lesions clinics.

PMID- 8295751
TI  - Syndrome X.

PMID- 8295752
TI  - Interaction of phenytoin and fluoxetine.

PMID- 8295753
TI  - Inadvertent use of Heaf tuberculin for Mantoux testing.

PMID- 8295754
TI  - Clinical leadership in control of melanoma.

PMID- 8295755
TI  - Skin sensitivity to sumatriptan.

PMID- 8295756
TI  - The validity of Maori hospital discharge statistics for ischaemic heart disease
      in New Zealand.
AB  - Data from an Auckland coronary heart disease register for the years 1983 to 1991
      have been used to assess the validity of routine national statistics on Maori
      hospital discharge rates for ischaemic heart disease. Ethnicity as recorded on
      the hospital admission record was compared with self defined ethnicity as
      recorded by register interviewers. Unlike routine New Zealand mortality
      statistics, where there is marked underreporting of Maori mortality, it appears
      that hospital discharge statistics are not markedly affected by misclassification
      of ethnicity. Approximately 12% of those classified on the admission record as
      Maori considered themselves to be of a different ethnicity, and 0.5% of those
      classified as 'other' considered themselves to be Maori. Because of the small
      proportion of the population (and of ischaemic heart disease deaths) who are
      Maori, the two misclassifications cancel out and the overall routinely reported
      hospital morbidity rates are similar to rates based on self reported ethnicity.
      For example, in 1990, routine national statistics show that there were 345 Maori
      hospital discharges or deaths due to ischaemic heart disease, and 8946 events
      among other ethnic groups. After adjustment using the register figures to reflect
      self defined ethnicity, the figures were 347 and 8944 respectively.

PMID- 8295757
TI  - Control of high cost medicines.

PMID- 8295758
TI  - The cost of tracking a cohort of women in a general practice using rubella immune
      status as an example.
AB  - AIM: To measure the cost of tracking for rubella immunisation status. METHOD: A 6
      month prospective cohort study tracking all 25 and 26 year old women registered
      with suburban middle class general practice. RESULTS: 357 women were registered
      as at 12 October 1992. 44% lived more than 3 km from the general practice
      building and 14% had no contact telephone. Culling the clinical records gave the
      general practice information on rubella status for 28% of women. Sending two
      letters and two telephone calls to the remainder resulted in an increase to 59%
      of women where the general practice had information about rubella status (chi 2 =
      71.26, df = 1, p < 0.001). An inability to contact women was the major reason why
      143 women did not have their rubella status known by the general practice.
      Information on rubella status was available in only 20% of women who had not
      given a contact telephone number to the general practice, compared to 67% of
      women who had given a contact telephone number (chi 2 = 38.38, df = 1, p <
      0.001). Culling records and sending one letter was the most efficient use of
      resources. The total cost per woman screened in this study was $9.94. CONCLUSION:
      More general practice research is needed to determine all the costs of screening
      for important medical conditions.

PMID- 8295759
TI  - Genetically engineered immunoconjugates: a dosimetric dilemma?

PMID- 8295760
TI  - 99Tcm-HMPAO brain SPECT in the evaluation of prognosis after surgical resection
      of astrocytoma. Comparison with other noninvasive imaging techniques (CT, MRI and
      201Tl SPECT).
AB  - High-grade astrocytoma represents the most common primary malignant brain tumour
      in the adult, and is associated with high morbidity and mortality rates. The aim
      of this study was to investigate the prognostic value of 99Tcm
      hexamethylpropyleneamine oxime (HMPAO) brain single photon emission computed
      tomography (SPECT) in predicting neurological function and tumour therapy
      response after surgical resection of astrocytoma. The correlation between 99Tcm
      HMPAO studies and other noninvasive methods [computed tomography (CT), magnetic
      resonance imaging (MRI) and 201Tl (SPECT)] was evaluated. The clinical population
      included 21 patients with previous surgical debulking of astrocytoma. All
      patients were evaluated with 99Tcm-HMPAO brain SPECT. Seven patients, who
      suffered progressive clinical deterioration after radiotherapy, underwent dual
      isotope SPECT imaging with 201Tl and 99Tcm-HMPAO. Neurological examinations and
      CT were performed in all patients. Magnetic resonance imaging was performed in
      seven patients. Prior to radiotherapy and/or chemotherapy, the patients with
      neurological improvement during the follow-up evaluation commonly showed less
      intense abnormal 99Tcm-HMPAO uptake than the patients without neurological
      improvement. In addition, after therapy none of the former patients had increased
      99Tcm-HMPAO uptake. Most patients without neurological improvement had evidence
      of high focal uptake. Computed tomography and MRI usually demonstrated
      pathological contrast enhancement regardless of the presence or absence of
      improvement of neurological function. Foci of high 201Tl accumulation were
      observed on SPECT images in five patients. In four of these patients, the 99Tcm
      HMPAO was greater than in normal brain, and in two patients the 99Tcm-HMPAO
      uptake was lower than in normal brain. One patient with decreased 99Tcm-HMPAO
      uptake in a medium-sized lesion had a normal 201Tl study. Our hypothesis that
      99Tcm-HMPAO SPECT may be useful for providing prognostic information after
      surgical debulking of astrocytoma seems to be promising. Further studies are
      needed to document this new important role of 99Tcm-HMPAO SPECT.

PMID- 8295761
TI  - Evaluation of a technique for the quantification of radioactivity and volume of
      an object using SPECT.
AB  - The technique of threshold determination using maximization of interclass
      variance (MIV) has been evaluated for the assessment of radioactivity and volume
      in single photon emission computed tomography (SPECT). The SPECT reconstruction
      incorporated scatter and attenuation correction using an attenuation map from
      computed tomographic (CT) images. The technique has been examined on a large
      number of phantom objects with both 99Tcm and 131I. Volume measurement of objects
      was performed using a variety of methods of applying the MIV technique. The
      standard error of volume estimation for the optimum method was 7.3 ml for 99Tcm
      and 15.3 ml for 131I. Activity was measured by expansion of the volume of
      interest representing the space occupied by the object to make allowance for
      limited SPECT resolution. The standard errors of the activity measurements were
      0.22 MBq for 99Tcm and 0.24 MBq for 131I.

PMID- 8295763
TI  - A simple method for studying lung ventilation.
AB  - A simple method of precisely administering a compact gas bolus during selectable
      portions of the inspiratory cycle was developed to examine certain fundamental
      attributes of lung physiology and ventilation. The method allows for a small,
      well-defined bolus to be delivered during different phases of inspiration in a
      precise fashion. A pneumatically driven three-way switching valve is synchronized
      to the breathing pattern and controls the interjection of radioxenon boli in the
      inspiratory stream, spiking a small portion of the inhaled breath. The 133Xe
      dispersion and redispersion in the lungs is mapped and the clearance followed.
      Regional differences are analysed to determine how ventilation might influence
      the development of lung diseases due to inhaled toxins. Scintillation imaging at
      20 frames s-1 allows near real-time characterization of the ventilation
      distribution. Novelty comes from the application of fast data gathering, the flow
      through valve design for delivery of tightly compacted boli and from tracing
      different fractions of the breath. The procedure involves low radiation exposure.
      An apparatus and method for acquiring data on lung filling and emptying not
      previously available is described. Potential applications are identified which
      may allow the re-examination of orthodox lung physiology.

PMID- 8295762
TI  - Difference in 201Tl accumulation on single photon emission computed tomography in
      benign and malignant thoracic lesions.
AB  - The difference in 201Tl-chloride (201Tl) accumulation on single photon emission
      computed tomography (SPECT) between 58 benign (58 cases) and 48 malignant (46
      cases) thoracic lesions, each of more than 20 mm in diameter was investigated. In
      the 34 benign and 48 malignant lesions depicted in both early (15 min) and
      delayed (3 h) images there was no significant difference in the mean early and
      delayed uptake ratios of lesion to normal contralateral lung between benign and
      malignant. However, the retention index in the lesion derived from (delayed ratio
      -early ratio)/(early ratio) x 100% showed a significant difference (benign -4.30
      +/- 13.6% versus malignant 23.3 +/- 18.9%, P < 0.01), indicating the poor 201Tl
      retention in the benign lesions. Using the criteria of nondepiction in the
      delayed image or a negative retention index, 81.1% accuracy and 95.2% predictive
      value for diagnosis of benign lesions were obtained. Thus, 201Tl SPECT appears to
      have potential usefulness in the diagnosis of benign thoracic lesions.

PMID- 8295764
TI  - Lung scan reporting language: what does it mean?
AB  - The aim of this study was to analyse the understanding of the verbal probability
      language used for communicating lung scan findings. A questionnaire providing a
      series of expressions of probability in lung scan reporting was sent to 211
      consultant nuclear medicine providers in the UK. Respondents were asked to
      estimate the probability of pulmonary embolism (PE) communicated by each
      reporting expression on a visual linear probability scale. Analysis of 135
      replies revealed a wide variation in the interpretation of the probability
      language. We suggest that different training, the nature of the probability scale
      itself and the difficulties of expressing a verbal report on a numerical scale
      are major reasons for this finding. We conclude that use of verbal probability
      language complicates the communication of PE risk and that likelihood ratios
      provide a logical alternative.

PMID- 8295765
TI  - Radioimmunoimaging of experimental arterial and venous thrombi in dogs with 99Tcm
      labelled monoclonal anti-activated platelet antibody SZ-51.
AB  - In canine experimental models of femoral arterial and venous thrombosis, the
      feasibility of thrombus imaging with 99Tcm-labelled monoclonal antibody SZ-51 to
      an alpha-granule membrane protein (GMP-140) on the surface of activated platelets
      was investigated. Both the arterial and venous thrombi were clearly discernible
      at 2 to 8 h after injection of 99Tcm-SZ-51. The suitable imaging time was 4 to 6
      h. These results were confirmed by ex vivo images of thrombosed arteries and
      veins followed by killing the dogs at 8 h postinjection of 99Tcm-SZ-51.
      Quantitative imaging analysis showed that the ratios between the thrombus and the
      opposite vessel were increased strikingly over time. The ratios of thrombus to
      blood or surrounding muscle were 57.09 +/- 12.24 and 177.46 +/- 9.00 for arterial
      thrombi and 6.43 +/- 4.70 and 83.22 +/- 68.98 for venous thrombi at the time of
      death. Radiolabelled antibody was cleared from the blood with T1/2 alpha of 16.25
      +/- 13.39 min and T1/2 beta of 7.28 +/- 1.15 h. These results show that it is
      feasible to detect noninvasively thrombus formation in vivo using 99Tcm-labelled
      monoclonal antibody SZ-51.

PMID- 8295766
TI  - [Changes in the macromolecular composition and organization of the cell nucleus
      during gameto-, embryo- and histogenesis].
AB  - Data about changes in the molecular organization of the cell nucleus during the
      organism development and tissue differentiation are summarized. The peculiarities
      of the nucleus organization of gametes, its changes in the course of
      fertilization and early embryogenesis are discussed. Data concerning different
      objects of developmental biology are reviewed separately. The data about tissue
      specificity of the chromatin structure and characteristic features of nuclei of
      nervous, muscle, epithelial, and connective tissue cells are also presented.
      Different levels of chromatin organization, i.e., the primary and secondary DNA
      structure, protein composition, nucleosomal and supranucleosomal structures, DNA
      supercoiling in chromatin domains, nuclear skeleton structures, are specifically
      concerned in each particular case.

PMID- 8295767
TI  - [The development of mouse embryos in vitro in a protein-free medium depending on
      the numbers of embryos in a microvolume of the medium].
AB  - We studied the development of mouse embryos in vitro depending on the number of
      embryos in a given microvolume of the Ham's F-10 medium without protein or with
      the addition of serum. The absence of serum from the culture medium did not
      affect the development of two-cell embryos cultivate in groups of 5-6 (about 90%
      embryos developed until the stage of blastocyst and over 50% left zona
      pellucida), but the development of single embryos in the protein-free medium
      proceeded significantly worse. Single two-cell embryos cultivated in the serum
      containing medium developed similar to embryos cultivated in groups. At the same
      time, no significant differences in development was found between eight-cell
      embryos cultivated individually or in groups of up to 10 embryos in the Ham's F
      10 medium, either in the presence of serum or without it (about 95% embryos
      developed until the stage of blastocyst and over 70% left zona pellucida). The
      increase in the number of cultivated embryos over 10 had the adverse effect on
      development of either two-cell or eight-cell embryos. The attachment of
      blastocysts to the substrate after leaving zona pellucida and growth of
      trophectoderm was observed only in the presence of serum. These results suggest
      that interaction between preimplantation embryos in culture can probably be
      mediated by factor(s) released by embryos into the medium. Serum appears to
      contain such factor(s). Sensitivity of embryos to the factor(s) apparently
      depends on the stage of development.

PMID- 8295768
TI  - [Aneuploidy frequency in the parthenogenetic activation of mouse tetraploid
      oocytes by ethyl alcohol].
AB  - We studied the frequency of aneuploidy in the parthenogenetic mouse embryos
      developed from tetraploid oocytes activated by treatment with 80% ethanol
      solution. The usual diploid mouse oocytes aged in vivo and in vitro were used as
      the control. Cytogenetic analysis showed that the frequency of aneuploidy in
      embryos obtained from the tetraploid oocytes (27%) is higher than that in
      parthenogenotes obtained from diploid oocytes aged in vitro (5%) or in vivo
      (16%). In the latter case, however, the difference is statistically
      insignificant. The possible causes of the observed differences are discussed.

PMID- 8295769
TI  - [The mitotic origin of binucleated cells in regenerating endothelium].
AB  - Regeneration of endothelium after the local cryodestruction of the aortic wall in
      rats was studied using quantitative methods (determination of the pool of
      proliferating cells after multiple injections of 3H-thymidine, of the mitotic
      index and proportion of binucleated cells, and cytophotometry of DNA content in
      cell nuclei). It is demonstrated that binucleate endotheliocytes are formed as
      the result of acytokinetic mitosis. According to our calculations, this mechanism
      completely provides for the increase in the proportion of binucleated cells
      observed in the regenerating endothelium on days from 2 to 6 after the operation.

PMID- 8295770
TI  - [V. A. Engel'gardt in the critical period of the life of our laboratory].

PMID- 8295771
TI  - [Tumor-associated myasthenia gravis and myasthenia syndrome].
AB  - Out of 700 patients operated on account of myasthenia gravis, 144 cases with
      tumours (20.57%) were evaluated. Classification took place in five groups: 1.
      Thymoma and myasthenia gravis; 2. Thymic cysts and myasthenia gravis; 3. Thymoma
      and latent myasthenia gravis; 4. Paraneoplastic myasthenia-syndrome; 5. Thymoma,
      myasthenia gravis and myasthenia-syndrome. Up-to-date classification of thymomas
      is: epithelioma with minimal, marked or overwhelming lymphatic reaction. Dark
      cell and light-cell epitheliomas equally associate with myasthenia. Concerning
      prognosis, location of the tumour to thymic capsula, surrounding, perithymic
      tissue is more important than the histologic structure of the tumour. Previous
      examination in the case of mediastinal tumour can reveal latent, mild myasthenia
      which was not known till that time. Term of postthymectomic myasthenia can be
      excluded on the basis of these examinations. Heterogeneity is considerable among
      myasthenia-syndromes concerning both histopathologic and clinical features. There
      is a double indication of operation in the case of myasthenia with tumour: the
      tumour and the disease. Good results can be achieved in myasthenia gravis
      associated with tumour by means of total operation, post-operative radiation and
      by other up-to-date therapeutical procedures. The results are hardly beyond those
      of non-tumours myasthenia gravis.

PMID- 8295772
TI  - [Comparative evaluation of dipyridamole and dobutamine 2-dimensional
      echocardiography in ischemic heart disease].
AB  - Dipyridamole and dobutamine stress were performed in the same 41 angiographically
      controlled patients. Both tests were followed by 2 dimensional-echocardiography.
      The dose of dipyridamole was 0.56 mg/kg/4 min. or 0.84 mg/kg over 10 min., while
      the dose of dobutamine was 10-20-30-40 and 40 micrograms/kg/min. over 3 min. each
      step. In addition, to reach the submaximal heart rate 0.25 mg/min Atropine was
      also injected for 4 minutes in 13 cases. One vessel disease was found in 15
      cases, and 2 vessel disease was in 2 cases. The number of coronarography negative
      cases was 24. The sensitivity, specificity, positive and negative predictive
      values for both tests were 70%, 91%, 85% and 81%, respectively. False positive
      results were observed in 2 cases and false negative ones were found in 5 cases,
      mainly at left anterior descendent stenosis. There was a good agreement between
      the wall motion abnormality and the anatomic localization of stenoses. Both non
      invasive tests are suitable for the diagnosis of ischaemic heart disease.

PMID- 8295773
TI  - [Treatment of childhood vesicoureteral reflux with sub-ureteral injection of
      teflon paste].
AB  - From March 1989 to october 1990, 35 refluxing ureters in 25 children were treated
      by submucosal injection of Teflon (STING). The overall success rate was 54% after
      the first injection. The authors detail the procedure and analyse their results
      which demonstrate that Teflon injection can be safe and effective treatment of
      vesicoureteral reflux in most cases can replace antireflux surgery.

PMID- 8295774
TI  - [Surgical treatment of an unusual anomaly of the subclavian artery].
AB  - Surgical treatment of an unusual abnormality of the subclavian artery. The author
      presents a case of a 36 year-old female admitted with complaints of weakness of
      the right hand. Doppler pressure on the right and left arms was 100 mmHg and 140
      mmHg respectively. Arteriography of the right subclavian artery showed a 6 cm
      long tortuous area with a significantly narrowed (average 61%, maximum 75%)
      lumen. Other major arteries originating form the aorta did not exhibit
      pathological alterations. At surgery an 8 mm bore Goretex prosthesis was
      centrally anastomosed end-to-side to the common carotid artery, and the narrowed
      subclavian artery was ligated under the branching of the vertebral artery. A
      pedunculated end-to-end anastomosis was performed with the subclavian artery. The
      patient was released complaint-free. After a 4-year follow-up period the radial
      artery is palpable, the pressure in both extremities shows no alterations. The
      described pathology is regarded a congenital vascular alteration, which has never
      been described in the literature.

PMID- 8295775
TI  - [Prominent figure in Hungarian dermatology: Soma Beck (1872-19300].

PMID- 8295776
TI  - [A forgotten physician of Debrecen: Daniel Zelizy (1847-1889)].

PMID- 8295777
TI  - [Helicobacter pylori positivity].

PMID- 8295778
TI  - [Medical help from space].

PMID- 8295779
TI  - The effectiveness of vibratory stimulation in anejaculatory men with spinal cord
      injury. Review article.
AB  - Most spinal cord injury (SCI) men have fertility problems caused by anejaculation
      and a decreased fertility of the ejaculate. There are several methods to induce
      ejaculation, such as vibratory stimulation and transrectal electrostimulation. In
      order to investigate the current state of knowledge about the effectiveness of
      vibratory stimulation and to prepare a controlled clinical trial we reviewed the
      available literature. Ten articles met our inclusion criteria. Articles were
      found by various strategies, such as computer searches and screening of relevant
      journals. We used a structured approach to evaluate these articles. In total 428
      patients had been treated with vibration. Sixty percent (257) of the patients
      responded to treatment, ie produced ejaculate. Because of methodological
      shortcomings in most studies it remains unclear whether there is a relationship
      between injury type, such as level and completeness of the injury, and the
      response rate. Semen analyses showed a large intersubject variation. From the
      data available, it could be concluded that the semen volume is usually normal,
      whereas sperm motility and morphology of spermatozoa were in most cases far from
      normal. Side effects of vibratory stimulation were reported in 6% of the
      patients. Semen could be used for various (assisted) reproductive technologies,
      eg artificial insemination, in vitro fertilisation and microinsemination.
      Therefore, it is very important to know which stimulation method is most
      effective in treating anejaculatory SCI men. This review of the literature shows
      that the effectiveness of vibratory stimulation remains unclear. New, well
      designed clinical trials as well as basic research activities might clarify the
      effectiveness of vibratory stimulation and transrectal electrostimulation.

PMID- 8295780
TI  - Complications and costs of management of acute spinal cord injury.
AB  - This study examined the complications and costs of management of patients with
      acute spinal cord injury (ASCI) in a regional, multidisciplinary acute spinal
      cord injury unit (ASCIU). Data were available to compute length of stay (LOS) on
      191 of the first 220 consecutive patients managed in this unit from 1974 to 1981.
      Specific formulae for assessing hospital and medical costs were developed based
      on a systems analysis approach. The statistical analysis included multiple
      regression analysis for determining the effect of the principal admission
      characteristics of ASCI patients, the main types of complications, and the
      methods of management. The effects of these variables on LOS, costs per day
      (CPD), and costs per stay (CPS) were determined. Age at admission, sex, and cause
      of accident had no effect on costs. As expected, increasing severity of injury to
      the spinal cord and to the vertebral column caused a significant increase in the
      mean LOS and CPS, and increasing total trauma load resulted in a significant
      increase in LOS and CPS. The LOS was shorter for patients admitted sooner after
      trauma. Respiratory, gastrointestinal, thromboembolic and genitourinary
      complications and decubitus ulceration were all associated with marked increases
      in LOS and CPS. The annual mean CPS decreased dramatically during the period of
      the study from 1974-81 due mainly to a decrease in LOS. Multiple regression
      analysis showed that severity and level of the spinal column and spinal cord
      injury, and the presence of complications had the most significant effects on
      duration and cost of care. The study also suggests that a specialized,
      multidisciplinary regional unit for ASCI patients is associated with a reduction
      in LOS and cost of care.

PMID- 8295781
TI  - Relief of spasticity in SCI men and women using rectal probe electrostimulation.
AB  - Although there are numerous approaches to the treatment of spasticity, many
      patients are still unable to find a satisfactory method of managing their spasms
      with acceptable side effects. In the course of our fertility studies using rectal
      probe electrostimulation (RPES) in SCI men to produce ejaculation, we observed
      that a majority of the men experienced significant relief of their spasticity for
      many hours. This report describes a prospective, single-blinded study of this
      phenomenon in six SCI men and three SCI women who underwent RPES a total of 71
      times. The mean age of the subjects was 28.2 years (21-41), the mean time from
      injury was 6.0 years (0.5-15); there were three paraplegic and six quadriplegic
      persons: four were Frankel class A and five were class B. Although all subjects
      had moderate to severe spasticity, only four took antispasm medications; one had
      undergone surgery for implantation of an epidural stimulator. The effectiveness
      of RPES on spasticity was evaluated by each subject for frequency of spasms and
      interference of daily activities and by independent, blinded assessors for tone,
      frequency of spasms and DTRs; four patients underwent quantitative videotape
      analysis of the pendulum test and two underwent somatosensory evoked potentials
      (SSEPs) to evaluate electrical activity in the central nervous system. Treatment
      variables included varying probe sizes and number of stimulations. All subjects
      experienced good to excellent decrease in tone, frequency of spasms and
      interference with ADL from 3 to 24 hours depending on treatment variables used.
      Mean duration of relief was 8.2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295782
TI  - Effects of induced hypothermia on somatosensory evoked potentials in patients
      with chronic spinal cord injury.
AB  - We have investigated the effects of mild whole body hypothermia on the amplitude
      and latency of somatosensory evoked potentials (SEPs) in control subjects (n =
      12) and patients (n = 15) with chronic compressive or contusive spinal cord
      injury (SCI). Mild hypothermia (-1 degree C) was induced by controlled
      circulation of propylene glycol through a 'microclimate' head and vest garment
      while reductions in oral and limb temperatures were monitored. Cooling induced a
      delayed onset and reduced amplitude of tibial nerve SEPs in control subjects. All
      SCI patients with recordable SEPs (n = 11) showed similarly delayed onset of the
      cortical response. In contrast to the controls, nine of the 11 SCI patients
      showed an increase in amplitude of cortical SEPs. In three of these patients the
      increase in amplitude exceeded 100% of the precooling values. The cooling-induced
      changes in SEP amplitude and latency reversed on rewarming for both groups. The
      cooling-induced increases in cortical SEP amplitude support the a priori
      hypothesis that cooling would enhance central conduction in some SCI patients
      with conduction deficits due to focal demyelination.

PMID- 8295784
TI  - Atypical syndromes caudal to the injury site in patients following spinal cord
      injury. A clinical, neurophysiological and MRI study.
AB  - Some patients with a cervical or a high thoracic spinal cord injury show atypical
      signs and symptoms such as atrophy of lower leg muscles, reduced tendon jerks or
      urinary retention, either persisting from the acute phase or developing in the
      course of time. A series of 35 patients was prospectively examined from this
      point of view with neurophysiological, urodynamic and MRI studies. Seven patients
      (20%) presented atypical findings; in two there was an isolated areflexic
      bladder, but no signs of functional or structural sacral damage were found. In
      five patients (14.2%) a definite cause for the sacral lesion could be detected.
      The syndrome caudal to the level of the lesion is neither obvious at the
      beginning nor immutable in time. Treatment requires to be adapted to the changing
      patterns of somatic and visceral activity.

PMID- 8295783
TI  - Creatinine, calcium, citrate and acid-base in spinal cord injured patients.
AB  - The aim of this work was to recognise factors responsible for reduced citrate
      excretion, previously reported in patients with spinal cord lesions and possibly
      related to the occurrence of urinary tract stone or catheter blockage. Inter
      alia, a reference range for creatinine in plasma (34-88 mumol/l) was also
      obtained. Two groups of subjects were studied. The first group consisted of 64
      male inpatients with spinal cord lesions and 20 male control subjects. The second
      group were 342 spinal patients who attended an outpatient clinic and 31 control
      subjects. Plasma calcium was within the normal range but higher in patients
      within 1 year of onset of the cord lesion than it was later or than was found in
      control subjects. Plasma pH and bicarbonate were within the normal range but
      higher in the patients than in the control subjects. When patients with urea
      splitting infection were omitted the patients had a higher urinary pH and a lower
      urinary ammonium than the controls. Urinary and plasma citrate were lower in the
      patients than in the controls. Urinary citrate was related to urinary potassium
      and creatinine clearance. Fractional renal tubular reabsorption of citrate did
      not differ between patients with normal renal function and control subjects.
      Patients with normal glomerular filtration had lower filtered load of citrate
      than the controls. The coincidence of relative alkalosis and reduced citrate
      excretion may be relevant to the understanding of catheter blockage and urinary
      stone formation in spinal cord injured patients.

PMID- 8295785
TI  - Testosterone-induced changes in phosphatidylcholine molecular species composition
      of Plasmodium chabaudi-infected erythrocytes.
AB  - This study is concerned with the influence of testosterone on the phospholipid
      class and the phosphatidylcholine molecular species composition of various
      fractions obtained from the blood of Plasmodium chabaudi-infected mice. Blood
      plasma, infected erythrocytes, isolated parasites and erythrocyte membranes
      isolated from both non-infected and infected erythrocytes in the form of ghosts
      were analysed. In general, the phospholipid classes remained unaffected, while
      the phosphatidylcholine (PC) molecular species composition showed differences
      after testosterone treatment. In infected erythrocytes, there was a decrease in
      16:0/20:4-PC and 18:0/20:4-PC and an increase in 16:0/18:2(16:0/20:3)-PC. The
      decrease of 16:0/20:4-PC was exclusively confined to parasites. The rise in
      16:0/18:2(16:0/20:3)-PC and the diminution of 18:0/20:4-PC occurred in the
      erythrocyte membrane of both infected ghosts and non-infected ghosts as well as
      in the blood plasma. It is suggested that these changes occur primarily in the
      plasma thereby influencing the erythrocyte membranes. The decrease in 16:0/20:4
      PC supports the view of the independence of the parasite from the biosynthetic
      lipid pathways of its host cell.

PMID- 8295786
TI  - Amelioration of murine cerebral malaria by dietary restriction.
AB  - CBA/T6 strain mice infected with Plasmodium berghei ANKA develop cerebral
      symptoms and die, with mononuclear cell attachment to the cerebral microvascular
      endothelium, petechial haemorrhages and breakdown of the blood-brain barrier,
      some 6-7 days post-inoculation. The effects of dietary restriction on this
      process were examined. Mice were fed ab libitum (Group 1) or their food was
      restricted to produce body weight loss of 1.0-2.0% (Group 2), 2.5-3.5% (Group 3),
      4.0-6.5% (Group 4) or 7.0-9.5% (Group 5) relative to Group 1. Dietary restriction
      reduced deaths caused by cerebral malaria from 100% in Group 1 to 47% (Group 2),
      43% (Group 3), 10% (Group 4) and 53% (Group 5). Restriction of food intake had no
      effect on (1) the progression of parasitaemia in infected mice (2) changes in
      haematocrit, spleen weight, total lymph node cell number or (3) peritoneal
      exudate cell number in either malaria-infected or uninfected mice. P. berghei
      ANKA infection did not significantly affect the proportion of lymph node
      leucocytes that were Thy-1+ T cells or CD8+ T cells, but did lead to significant
      increases in the CD4+ and B cell populations. Dietary restriction alone increased
      the lymph node CD4+ cell population but did not affect the increase in B cells in
      malaria-infected mice. P. berghei ANKA infection and dietary restriction together
      did not lead to increased CD4+ cell numbers in lymph node leucocytes. The in
      vitro proliferative response to isolated lymph node cells to concanavalin A or
      phorbol myristate acetate plus ionomycin was measured and found to be identical
      in all treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295787
TI  - Comparisons between microvascular changes in cerebral and non-cerebral malaria in
      mice, using the retinal whole-mount technique.
AB  - CBA/T6 mice inoculated with Plasmodium berghei ANKA strain (PbA) exhibited
      cerebral symptoms and died from cerebral malaria 6-8 days p.i. whereas DBA/2J
      mice developed (around days 6-9) a non-fatal cerebral malaria, with milder
      cerebral symptoms, and died between days 15 and 22 from other malaria-related
      complications. When inoculated with P. berghei K173 (Pb) these mouse strains did
      not develop cerebral malaria. These mouse/parasite strain combinations were used,
      in conjunction with the retinal whole-mount technique, to elucidate factors
      critical in the pathology of murine cerebral malaria. CBA/T6 mice infected with
      PbA (PbA-CBA mice) demonstrated mild changes in vascular permeability as early as
      days 2-3, prior to the appearance on day 5 of cerebral symptoms, whereas mice
      with non-cerebral malaria did not show any vascular permeability changes until
      the very late stage of the disease (days 14-22). In the PbA infections,
      progressive deterioration of endothelial barrier properties, demonstrated by
      Evans' Blue leakage both generally and from specific focal areas, as well as a
      developing monocytosis and adherence of mononuclear cells to the endothelium of
      the retinal vessels continued until death (in CBA/T6 mice) or resolution (in
      DBA/2J mice). Adherent monocytes, particularly in PbA-CBA mice, were associated
      with reduced Hoechst staining of individual endothelial cells and a banking up
      proximally of both parasitized and non-parasitized blood cells in the small blood
      vessels, often with accompanying focal leakage of Evans' Blue from the retinal
      vessels. The occurrence and severity of these early changes in the
      microcirculation correlated with the subsequent development of cerebral symptoms.
      Monocyte margination appeared to be the most significant factor associated with
      the development of cerebral symptoms.

PMID- 8295788
TI  - Experimental infection of athymic mice with the human microsporidian Nosema
      corneum.
AB  - Athymic mice (BALB/c nu/nu/Ola/Hsd) were experimentally infected
      intraperitoneally with Nosema corneum spores. Infection was monitored in the
      first and second weeks post-infection. The liver, spleen, kidney, intestine,
      lung, heart, brain and eye were collected. Quantification of infection in each
      organ using three different techniques gave approximately the same pattern of
      infection. Infection increased with time. Histological observations were made on
      the sites of infection in each organ. All organs were infected, the liver being
      the most heavily infected. The eye was infected in the retina in contrast to the
      cornea which was the site of infection in the original host. The present study of
      N. corneum in athymic mice has shown that this system could also be used to study
      host-parasite relationships and serve as a model for testing therapeutic agents.
      Previously the only microsporidian serving as a suitable model for human
      microsporidiosis was Encephalitozoon cuniculi.

PMID- 8295789
TI  - Characterization of a Leishmania antigen associated with cytoplasmic vesicles
      resembling endosomal-like structure.
AB  - In the present study we have used antibodies to Leishmania major promastigote
      antigens which were eluted from a glutathione-agarose column (LmGbp) and could
      identify several parasite components among different Leishmania species by using
      immunoprecipitation and Western blot techniques. The results also showed that
      some of LmGbp are present among the molecules released into the culture medium.
      Moreover, immunofluorescence assays clearly demonstrated that LmGbp are expressed
      by intracellular amastigotes. The electron micrographs of thawed cryosections of
      L. major-infected cells revealed that the antigens were associated with the
      membrane of the phagocytic vacuole. Moreover, the Western blot technique allowed
      us to identify, using other Leishmania species extracts and anti-LmGbp
      antibodies, a major polypeptide of an apparent molecular mass of 66 kDa.
      Immunofluorescence studies suggested that the 66 kDa polypeptide is associated
      with intracytoplasmic vesicles. Cryosections of Leishmania promastigotes improved
      the fine structure preservation of the organelles and enabled a number of
      features to be seen, particularly the structures considered as vesicles, which
      appeared as a complex tubulo-vesicular structure resembling mammalian cell
      endosomes and Leishmania organelles previously named 'megasomes'. Further studies
      using antibodies against the native 66 kDa protein will be needed to investigate
      the localization of the protein at the ultrastructural level and to follow its
      intracellular vesicular traffic.

PMID- 8295790
TI  - Enzymatic amplification of mini-exon-derived RNA gene spacers of Leishmania
      donovani: primers and probes for DNA diagnosis.
AB  - The multicopy mini-exon-derived RNA (med RNA) locus of Leishmania donovani was
      enzymatically amplified by the polymerase chain reaction (PCR). The major 180 bp
      PCR product contained conserved med RNA gene sequences flanking the variable
      intergenic spacer from the med RNA gene tandem repeat. The oligonucleotide
      primers cross-reacted with other Leishmania species. In serial dilution
      experiments, positivity in the PCR assay was observed down to the genomic DNA
      equivalent of less than a single Leishmania cell. When the major PCR products
      from Indian L. donovani isolates were cloned and used as probes in dot
      hybridization analyses, they discriminated between L. donovani and L.
      amazonensis, L. major and L. infantum under high stringency conditions. DNA from
      spleen biopsies and blood samples of confirmed kala azar patients was positive,
      as were two skin biopsies from patients with post-kala azar dermal leishmaniasis
      (PKDL). These observations demonstrate that PCR amplification of med RNA
      intergenic spacers is sufficiently sensitive for clinical diagnosis of kala azar
      and PKDL, and furthermore, that cloned intergenic spacer probes may be useful for
      identification and classification of L. donovani.

PMID- 8295791
TI  - Host-related DNA sequences are localized in the body of schistosome adults.
AB  - The localization of host (mouse)-related DNA sequences in the adults and
      cercariae of Schistosoma japonicum and S. mansoni was examined by in situ
      hybridization using 32P-labelled probes. The hybridization signals to the
      sequences of the mouse type C and type A retroviruses were clearly observed in
      the subtegumental layer and inner tissues of S. japonicum adults. In contrast, it
      was hard to find any signals to these sequences in S. mansoni adults. Distinct
      signals to the env-specific region of the mouse ecotropic type C retrovirus were
      observed in the subtegumental layer and inner tissues of S. mansoni adults. No
      signal to the sequence of the mouse type B retrovirus was found on the sections
      of either schistosome adult. The signals to the sequence of the genomic clone
      SmM51 derived from male S. mansoni were found in the tissues of both the
      schistosome adults. The signals to the sequences of the mouse type A and env
      specific region of ecotropic type C retroviruses were not seen in the cercariae
      of each species, whereas the signals to the sequence of SmM51 were detected in S.
      mansoni cercariae. These observations suggest that host-related DNA sequences
      might be incorporated unequally into the schistosome genome during development in
      the final host.

PMID- 8295792
TI  - Dynamics of gastropod infection by first-stage larvae of protostrongylid
      nematodes--a model.
AB  - For the description of the dynamics of snail infection by the 1st-stage larvae of
      protostrongylid nematodes, Skorping (1988) used the miracidia-snail model
      (Anderson, 1978). Here it is shown that, in contrast to miracidia, in
      protostrongylids the instantaneous rate of infection, alpha, is strongly
      dependent on the experimental design (factors like host size and size of the
      experimental arena). With respect to this, Anderson's model is modified by
      incorporation of the experimental design. The parameter alpha in its new sense as
      the rate of penetration (probability that the infective larva will penetrate into
      the host during a time unit) is shown to remain dependent, although much less so,
      on the experimental design. Only the inclusion of the assumed effect of mucus,
      which decreases the rate of penetration, yields a parameter alpha 0 (the initial
      rate of penetration), which is completely independent of the design of the
      experiment, is species-specific, and also gives the best fit to the empirical
      data. As the above-mentioned factors can strongly influence the value of the
      instantaneous rate of infection in the laboratory experiments, alpha 0 is more
      suitable as a measure of either the larval infectivity for the snail or snail
      susceptibility to infection by the protostrongylid larvae.

PMID- 8295793
TI  - A freeze-fracture study of the cuticle of adult Nippostrongylus brasiliensis
      (Nematoda).
AB  - The surface of the cuticle of adult Nippostrongylus brasiliensis has been studied
      by means of the freeze-fracture technique and by transmission electron
      microscopy. Some of the surface coat appears to have been shed from the surface
      of the cuticle of adults fixed in situ in the intestine of its host and from the
      surface of individuals removed from the intestine and freeze-fractured. Freeze
      fracturing the cuticle of individuals removed from the host has shown that this
      surface coat varies in thickness from 30 to 90 nm. The epicuticle is about 20 nm
      thick and cleaves readily to expose E- and P-faces. The P-face of the epicuticle
      possesses a small number of particles, similar to intra-membranous particles,
      whilst the E-face possesses a few, widely scattered depressions. Despite the
      presence of these particles the epicuticle is not considered to be a true
      membrane. Freeze-fracturing the remainder of the cuticle has confirmed its
      structure as described by conventional transmission electron microscopy. Clusters
      of particles on the P-face of the outer epidermal (hypodermal) membrane and
      corresponding depressions on the E-face of the membrane are though to be
      associated with points of attachment of the cuticle to the epidermis
      (hypodermis). No differences in appearance of the cuticle and its surface layers
      were observed in individuals taken from 7-, 10-, 13- and 15-day infections.

PMID- 8295794
TI  - Acetylcholinesterase in infective-stage larvae of Haemonchus contortus,
      Ostertagia circumcincta and Trichostrongylus colubriformis resistant and
      susceptible to benzimidazole anthelmintics.
AB  - The amounts of acetylcholinesterase (AChE) in homogenates of infective-stage
      larvae of strains, from different countries, of Haemonchus contortus, Ostertagia
      circumcincta and Trichostrongylus colubriformis resistant or susceptible to
      benzimidazole (BZ) anthelmintics, were compared using a rapid colorimetric assay.
      The levels of AChE were much greater in those strains which were BZ-resistant
      than in BZ-susceptible populations. The larvae of susceptible and resistant H.
      contortus contained less AChE than did the larvae of the other two species. One
      way analysis of variance showed that the observed differences between susceptible
      and resistant strains were significant in each of the species studied. It is
      suggested that the extra enzyme may act as an anthelmintic-detoxifying enzyme,
      may inactivate the active site of the anthelmintic or may prevent binding of the
      anthelmintic to its receptor.

PMID- 8295795
TI  - Single juveniles of the potato cyst nematodes Globodera rostochiensis and G.
      pallida differentiated by randomly amplified polymorphic DNA.
AB  - Random amplified polymorphic DNA (RAPD) offers a potential basis for the
      development of a diagnostic assay to differentiate the potato cyst nematode
      species Globodera rostochiensis and G. pallida. Nine decamer primers have been
      tested for their ability to amplify species-specific DNA sequences. Primer OPG-05
      produced 2 discrete DNA fragments, which were consistently present in 5 G.
      rostochiensis populations and absent in 5 G. pallida populations. These fragments
      were detectable in single females as well as in single 2nd-stage juveniles. Their
      amplification is extremely efficient, and reproducible over a wide range of
      template concentrations. One-fifth of a single juvenile is sufficient to generate
      reproducible RAPD markers. The amplification from single juveniles requires no
      DNA isolation. The use of a crude homogenate does not impair the polymerase chain
      reaction.

PMID- 8295796
TI  - Historic origins and role of pediatric anesthesiology in child health care.

PMID- 8295797
TI  - Preoperative and postoperative fasting in children.
AB  - This article addresses the preoperative fast in the context of its historic
      background, the physiology of gastric emptying, and recent clinical studies. A
      rationale is developed for minimizing the traditional preoperative fasting
      interval for elective surgery. The timing and the necessity for patients to
      resume ingesting clear liquids in the postoperative period is also explored.

PMID- 8295798
TI  - Anesthetic implications of an upper respiratory infection in children.
AB  - Pediatricians and pediatric anesthesiologists are frequently confronted with the
      dilemma of a child scheduled for elective surgery with or recently recovered from
      an upper respiratory tract infection. Modifications of routine anesthetic
      practice may decrease but not eliminate risks of associated complications.
      Guidelines for the evaluation and triage of these children are presented.

PMID- 8295799
TI  - Obstructive sleep apnea, control of ventilation, and anesthesia in children.
AB  - Pathologic disturbances in breathing in children become clinically apparent in
      the syndrome of obstructive sleep apnea. The surgical approach to this syndrome
      is often removal of hypertrophied tonsils and adenoids. The preoperative,
      operative, and postoperative concerns with special attention to the role of
      anesthesia are reviewed.

PMID- 8295800
TI  - Perioperative approach to children.
AB  - There has been a tremendous amount of progress in the perioperative approach to
      the child since Levy wrote "Psychic trauma of operations in children and a note
      on combat neurosis" nearly 50 years ago. Recognition of prolonged behavioral
      derangements following the anesthetic-surgical-hospital experience and the
      prominent role that the parent and physician play in modifying these have
      dramatically changed the contemporary pediatric perioperative care. Of paramount
      importance is the psychological preparation of family and child. With increasing
      outpatient or same-day admission surgery and free-standing surgical centers,
      preoperative preparation will, of necessity, increasingly become the
      responsibility of the pediatrician.

PMID- 8295801
TI  - Pediatric airway in health and disease.
AB  - The most common cause of pediatric anesthetic morbidity is the failure to
      adequately oxygenate. Problems with pediatric airways are the major cause of this
      inability to provide adequate oxygenation. Problems with pediatric airways and
      the diseases that affect them require not only knowledge about their
      pathophysiology but also considerable hands-on experience and respect for the
      complications that subsequently occur. It is hoped that by sharing knowledge and
      experiences, pediatricians can improve the care all of us strive to give our
      young patients.

PMID- 8295802
TI  - Anesthesia and apnea. Perioperative considerations in the former preterm infant.
AB  - Former preterm infants younger than 44 weeks postconceptual age are at increased
      risk for developing postoperative apnea and PB. When surgery cannot be deferred
      until the infant is developmentally more mature, several measures should be taken
      to minimize the risk of ventilatory dysfunction. First, outpatient surgery is not
      advisable for infants younger than 44 weeks postconceptual age. All infants
      should be admitted to the hospital and monitored for apnea and bradycardia for at
      least 12 to 18 hours after surgery. Second, we recommend the use of intravenous
      caffeine base 10 mg/kg in all infants at risk for postoperative apnea following
      general anesthesia. Preliminary studies of a small number of patients indicate
      that spinal anesthesia without sedation is associated with less apnea than is
      general anesthesia or spinal anesthesia with ketamine sedation. This option
      warrants further consideration. Infants with anemia of prematurity, generally a
      benign condition, are at increased risk for postoperative apnea. It is therefore
      preferable to delay elective surgery and supplement the feeds with iron until the
      Hct is above 30%. When surgery cannot be deferred, anemic infants must be
      observed and monitored carefully in the postoperative period.

PMID- 8295803
TI  - The night after surgery. Postoperative management of the pediatric outpatient-
      surgical and anesthetic aspects.
AB  - Outpatient or "ambulatory" anesthesia and surgery has revolutionized the way
      surgery is practiced in the United States. Safe, reliable, inexpensive, and
      convenient outpatient surgery is an attractive option for parents, children,
      health care providers, and insurers.

PMID- 8295804
TI  - Malignant hyperthermia.
AB  - Major advances have occurred in the management of MH since this disorder was
      first described. Despite the initially high mortality, deaths secondary to MH
      have dramatically decreased over the past 15 years, which is due in large part to
      the discovery of efficacious therapy. It is also a result of ever-increasing
      awareness and appreciation of the syndrome by physicians, other health care
      providers, and patients. Research has provided many answers to questions about
      the pathologic mechanisms of this disorder, and an animal model exists for
      testing new therapies; however, many questions remain. It is hoped that future
      investigations such as advances in genetic mapping may provide a specific,
      noninvasive method of predictive testing. It is possible that a complete
      understanding of MH and its mechanisms could teach us more about the ways
      anesthetic agents work. For now, identifying individuals at risk, rigorously
      avoiding exposure to potential anesthetic triggering agents in MH-susceptible
      patients, and promptly recognizing and treating unexpected MH episodes are the
      primary means of reducing morbidity and mortality from MH. Interested and
      informed clinicians and families are the patient's best allies against MH.

PMID- 8295805
TI  - Morbidity and mortality in pediatric anesthesia.
AB  - This article reviews specific considerations for greater anesthetic mortality in
      the first year of life as well as significant differences in pediatric anesthetic
      morbidity associated with routine anesthetic management. Clinical conditions such
      as upper respiratory tract infection, congenital heart disease, and muscle
      disease are addressed. Loss experience suggests a different profile for pediatric
      anesthesia.

PMID- 8295806
TI  - Sedation for the pediatric patient. A review.
AB  - Safe sedation of a pediatric patient requires a thorough knowledge of the
      pharmacokinetics and pharmacodynamics of the drugs used to sedate the patient and
      the skills necessary to deal effectively with potential adverse events as a
      result of the sedation. The Sedation Guidelines of the American Academy of
      Pediatrics are reviewed. Emphasis is placed on monitoring and appropriate
      selection of drugs.

PMID- 8295807
TI  - Pharmacology of pain management.

PMID- 8295808
TI  - Neuromuscular blocking drugs in infants and children.
AB  - Neuromuscular blocking drugs are valuable adjuncts to the practice of pediatrics.
      Monitoring of drug effects is technically more difficult in the younger patient.
      Nevertheless, careful observation of drug effects will improve the usefulness of
      NMB and safeguard the patient from prolonged weakness. Although there are
      differences in neuromuscular function with age in the pediatric age range, the
      differences between the NMB currently available are greater than the differences
      between the patients. Thus, the only uniform finding across age and all drugs is
      that onset of drug effect is more rapid in the infant than in the child when
      circulatory function is normal. In general, children require more of all NMB on a
      mg/kg basis than do infants or adults to obtain the same effect. Children recover
      from NMB more rapidly than do patients of other ages. Infants, however, may
      recover more rapidly than do any other patients from the effects of drugs such as
      mivacurium which are metabolized in the plasma. Tables 4 and 5 summarize doses,
      onset of action, and duration of NMB. Please note in Table 4 that succinylcholine
      is only used for endotracheal intubation, whereas the other nondepolarizing
      muscle relaxants can be used for endotracheal intubation or to maintain some
      degree of muscle paralysis in the child whose trachea is already intubated.
      Nondepolarizing muscle relaxants (e.g., mivacurium, ORG 9426, atracurium,
      vecuronium) are used both for initial bolus for endotracheal intubation and
      maintenance of muscle relaxation. Long-acting drugs (e.g., pancuronium,
      pipecuronium, and doxacurium), however, are used more commonly in small
      incremental doses to maintain muscle paralysis in patients already intubated. The
      advantages of these long-acting drugs are minimal cardiovascular side effects
      (i.e., tachycardia or hypotension from histamine release) and longer dosing
      interval. In all children, the dosing interval should be adjusted to the needs of
      the individual. In children with renal insufficiency or in those receiving drugs
      which impair neuromuscular function (e.g., aminoglycosides), the interval at
      which supplemental doses are required is longer than normal.

PMID- 8295809
TI  - Preoperative evaluation of children.
AB  - Preoperative evaluation and preparation are directed toward minimizing the
      intrinsic risks of anesthesia and surgery by having the child in the healthiest
      possible condition prior to surgery. The pediatrician can contribute to this goal
      by understanding the effects of general anesthesia on the physiology of children.
      This knowledge allows an appreciation of the anesthesiologists' concerns
      regarding underlying diseases, which may seem "stable" (and, therefore, of little
      present concern to the pediatrician) but which may have grave consequences during
      anesthesia. The preoperative evaluation is designed to ensure that the child's
      preoperative needs may be met by providing the anesthesiologist both qualitative
      and quantitative information regarding the child's state of health and disease.
      The relationship between the child, parents, and pediatrician places the
      pediatrician in an ideal position to prepare families for their children's
      surgical experience.

PMID- 8295810
TI  - Overview of the pharmacology of clarithromycin suspension in children and a
      comparison with that in adults.
AB  - The pharmacokinetics of clarithromycin after oral administration of
      clarithromycin granules for suspension formulation were investigated in adult
      volunteers and pediatric patients. A 250-mg single dose study conducted in adults
      revealed that the extent of absorption of clarithromycin from the suspension
      formulation was not significantly different from that of the reference tablet
      formulation, whereas the extent of formation of the active 14-hydroxy (14-OH)
      metabolite was significantly lower with the suspension formulation. In addition
      coadministration of the suspension formulation with food did not significantly
      alter the extent of absorption of clarithromycin or formation of the 14-OH
      metabolite. A single/multiple dose study conducted in adults revealed a delay in
      the time to attain peak plasma clarithromycin and 14-OH metabolite concentrations
      after suspension administration as compared with data obtained after tablet
      administration in previous studies. Steady state was achieved by Dose 5 in the
      multiple dose phase (250 mg every 12 hours for seven doses). In addition the mean
      plasma concentration-vs.-time data after suspension administration compared
      favorably with that noted after multiple oral dose administration of 250-mg
      tablets in adults. A single/multiple dose study conducted in pediatric patients
      revealed that coadministration of the suspension formulation with food did not
      significantly alter the extent of absorption of clarithromycin or formation of
      the 14-OH metabolite. During the multiple dose phase (7.5 mg/kg every 12 hours
      for 4 or 5 days), mean plasma concentration-vs.-time data compared favorably with
      that noted after multiple oral dose administration of 250-mg and 500-mg tablets
      in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295811
TI  - Comparative safety and efficacy of clarithromycin and cefadroxil suspensions in
      the treatment of mild to moderate skin and skin structure infections in children.
AB  - A prospective, randomized, single (investigator) blind multicenter study was
      performed to compare the safety and efficacy of clarithromycin and cefadroxil
      oral suspensions in the treatment of mild to moderate skin and skin structure
      infections in children. Male and female patients ages 6 months to 12 years were
      enrolled at 24 study centers in the United States. Patients had signs and
      symptoms consistent with mild to moderate skin or skin structure infections
      judged suitable for oral antimicrobial therapy. Clarithromycin oral suspension
      was given to 118 children in a dose of 7.5 mg/kg (maximum of 500 mg) twice daily;
      cefadroxil oral suspension was given to 113 children in a dose of 15 mg/kg
      (maximum of 1000 mg) twice daily. Among clinically evaluable patients clinical
      success rates (cure plus improvement) were 96% (71 of 74) for clarithromycin and
      98% (83 of 85) for cefadroxil (P = 0.664). Bacteriologic cure rates in evaluable
      clarithromycin and cefadroxil patients were 96% (72 of 75) and 99% (89 of 90),
      respectively (P = 0.331). Pathogen eradication rates based on 204 evaluable
      pathogens were 97% in the clarithromycin group and 99% in the cefadroxil group (P
      = 0.326). Adverse events were mild or moderate and were reported in 25% of
      clarithromycin and 35% of cefadroxil patients (P = 0.085). In both groups adverse
      events involved primarily the digestive tract. No significant laboratory changes
      were noted. Clarithromycin oral suspension appears to be a safe and effective
      alternative to cefadroxil for the treatment of pediatric skin and skin structure
      infections.

PMID- 8295812
TI  - Clarithromycin vs. amoxicillin suspensions in the treatment of pediatric patients
      with acute otitis media.
AB  - Clarithromycin is a new macrolide antibiotic that is active in vitro against a
      variety of organisms that are responsible for acute otitis media in children. The
      parent compound is metabolized to microbiologically active 14-hydroxy
      clarithromycin, which is especially active against Haemophilus influenzae. The
      safety and efficacy of clarithromycin and amoxicillin suspensions were compared
      in the treatment of acute otitis media in children 1 to 12 years of age
      inclusive. This was a Phase III, single blind (investigator-blind), randomized,
      multicenter clinical trial. Clarithromycin oral suspension was given in a dose of
      7.5 mg/kg (maximum, 500 mg) twice daily, and amoxicillin suspension in a dose of
      20 mg/kg (maximum, 750 mg) was given twice daily for 7 to 10 days in a 1:1 ratio.
      Clinical evaluations were performed pretreatment, within 48 hours posttreatment
      and 10 to 14 days posttreatment. Myringotomy was performed in every child to
      obtain a microbiologic sample pretreatment and at subsequent visits as clinically
      indicated. A total of 79 children were enrolled, 39 in the clarithromycin and 40
      in the amoxicillin treatment group. Thirty-two children were excluded from the
      efficacy analysis for various reasons. Clinical success (cure and improvement)
      rates at 0 to 4 days posttreatment were 93% for clarithromycin and 90% for
      amoxicillin (P > 0.999). Altogether 17 children (10 receiving clarithromycin, 7
      receiving amoxicillin) experienced some adverse event, with gastrointestinal
      disorders being the most common complaint. No clinically significant differences
      in laboratory tests were found between the groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8295813
TI  - Comparative safety and efficacy of clarithromycin and amoxicillin/clavulanate in
      the treatment of acute otitis media in children.
AB  - Clarithromycin is a new macrolide antibiotic with a wide spectrum of activity
      that includes the pathogens commonly causing pediatric otitis media. This
      randomized, investigator-blinded, multicenter trial compared the safety and
      efficacy of clarithromycin and amoxicillin/clavulanate in the treatment of acute
      otitis media in patients ages 6 months to 12 years. A total of 338 patients with
      acute otitis media diagnosed by otoscopy were randomized to receive
      clarithromycin 7.5 mg/kg twice daily, maximum 500 mg twice daily (n = 161), or
      amoxicillin/clavulanate 13.3 mg/kg three times daily, maximum 500 mg three times
      daily (n = 177), for 10 days. Treatment groups were comparable with respect to
      demographics, severity of infection and number of previous episodes. Efficacy was
      assessed by clinical examination performed within 48 hours of finishing study
      medication. A successful clinical response was seen in 90% (121 of 135) of
      evaluable clarithromycin patients vs. 92% (133 of 145) of evaluable
      amoxicillin/clavulanate patients (P = 0.681). Clinical failure or relapse
      (Posttreatment Days 0 to 4) occurred in 10% (14 of 135) of clarithromycin-treated
      patients vs. 8% (12 of 145) of amoxicillin/clavulanate-treated patients.
      Gastrointestinal adverse events were the most commonly reported in both groups.
      Of these events diarrhea was the most frequent, occurring in 12% (19 of 161) of
      clarithromycin and 32% (57 of 177) of amoxicillin/clavulanate-treated patients (P
      < 0.001). These results indicate that the efficacy of clarithromycin oral
      suspension was comparable with amoxicillin/clavulanate oral suspension in the
      treatment of acute otitis media in children. Clarithromycin was better tolerated
      than amoxicillin/clavulanate with a lower incidence of gastrointestinal side
      effects.

PMID- 8295814
TI  - Clarithromycin and cefaclor suspensions in the treatment of acute otitis media in
      children.
AB  - The safety and efficacy of a new oral suspension formulation of clarithromycin
      were evaluated in this multicenter, Phase III, single blind, comparative trial in
      379 children ages 6 months to 12 years with signs or symptoms of acute otitis
      media. Children were randomized to receive a 10-day course of clarithromycin oral
      suspension (7.5 mg/kg; maximum, 500 mg) or cefaclor oral suspension (20 mg/kg;
      maximum, 500 mg) twice daily. Specific clinical response criteria were developed
      based on pretreatment signs and symptoms and results of tympanometry. Of the 379
      enrolled patients 281 (74%) were evaluable (clarithromycin, 150; cefaclor, 131).
      There were no demographic differences between the two groups. Fifty percent of
      the patients had 2 to 4 episodes of otitis media (including the current episode)
      in the past 12 months; 63% of the patients had an infection of moderate severity.
      Clarithromycin and cefaclor suspensions were similarly effective for the
      treatment of acute otitis media. Clinical success (cure, cure with effusion or
      improvement) was achieved in 86% of clarithromycin-treated patients and 90% of
      cefaclor-treated patients. The majority of bacterial isolates for which
      susceptibility results were available were fully or moderately susceptible to the
      study drugs (96% clarithromycin, 92% cefaclor). Both drugs were well-tolerated;
      adverse events considered probably study drug-related were reported by 30 (15%)
      of clarithromycin recipients and 31 (17%) of cefaclor recipients. There were no
      significant differences between the groups in the numbers of patients reporting
      events that were thought to be related to study medication.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8295815
TI  - Comparison of clarithromycin and penicillin VK suspensions in the treatment of
      children with streptococcal pharyngitis and review of currently available
      alternative antibiotic therapies.
AB  - In a randomized investigator-blinded study, 506 children ages 6 months to 12
      years with positive rapid direct antigen tests for Group A beta-hemolytic
      Streptococcus (GABHS) received treatment with either clarithromycin suspension,
      7.5 mg/kg twice daily, or penicillin VK suspension, 13.3 mg/kg three times per
      day for 10 days. Signs and symptoms of pharyngitis or tonsillitis were evaluated
      and throat cultures were obtained before treatment, once during treatment and 4
      to 6 days and 19 to 25 days posttreatment. All GABHS isolates were susceptible in
      vitro to clarithromycin. Successful clinical responses at the end of treatment
      were demonstrated in 169 of 176 (96%) evaluable clarithromycin-treated patients
      and 179 of 191 (94%) evaluable penicillin-treated patients. GABHS was
      successfully eradicated at end of treatment in 168 of 183 (92%) evaluable
      clarithromycin-treated patients compared with 162 of 199 (81%) evaluable
      penicillin-treated patients (P = 0.004). There were no significant changes in
      hematologic or serum chemistry parameters in either group. Both drugs were well
      tolerated. The incidence and nature of adverse events were similar in the
      clarithromycin and penicillin groups, except for gastrointestinal complaints
      reported in 35 of 250 (14%) clarithromycin recipients compared with 12 of 256
      (5%) penicillin recipients (P < or = 0.001). The results indicate that twice
      daily clarithromycin was as safe and effective as three times daily penicillin VK
      in the treatment of children with streptococcal pharyngitis or tonsillitis.
      Clarithromycin was statistically superior to penicillin VK in the eradication of
      GABHS.

PMID- 8295816
TI  - Overview of the safety profile of clarithromycin suspension in pediatric
      patients.
AB  - Results of preclinical studies conducted to characterize the safety of
      clarithromycin oral suspension in juvenile mice, rats and dogs as compared with
      that in adult animals indicate that there is no enhanced risk in younger animals.
      Adverse events in these preclinical studies mainly involved decreased body and
      increased liver and kidney weights. The safety profile of clarithromycin
      suspension also has been evaluated in Phase II (pharmacokinetic) and III
      (clinical) United States and international clinical trials conducted in pediatric
      patients. The most frequently reported adverse events occurring among the 1676
      patients studied who received clarithromycin suspension in Phase III trials
      included diarrhea (7%), vomiting (6%), abdominal pain (2%), headache (2%) and
      nausea (1%). Adverse events were not serious and were usually rapidly reversible.
      Adverse event rates did not vary with sex or race. Overall adverse event rates
      were generally similar to those of comparator beta-lactam suspensions (i.e.
      amoxicillin, amoxicillin/clavulanate, penicillin VK, cefaclor, cefadroxil). With
      regard to specific gastrointestinal events, however, clarithromycin was better
      tolerated than amoxicillin/clavulanate whereas penicillin VK showed a lower
      incidence of gastrointestinal events. Overall clarithromycin oral suspension
      appears to be safe and well-tolerated, making it suitable for use in the
      pediatric population.

PMID- 8295817
TI  - Clarithromycin: where do we go from here?
AB  - Clarithromycin is a new macrolide with a broad spectrum of activity against Gram
      positive cocci, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma,
      Chlamydia and selected Mycobacteria, Legionella and protozoa. The drug has a half
      life of more than 4 hours and thus can be administered in a twice daily schedule.
      Clarithromycin is well-tolerated in children and adults and produces fewer
      gastrointestinal side effects than erythromycin. High concentrations of the drug
      are achieved in plasma and in cells and tissues including tonsil, lung and middle
      ear fluids. Clinical efficacy has been demonstrated in randomized multicenter
      trials of infants and children with acute otitis media, streptococcal pharyngitis
      and infections of skin and skin structures. Results of these comparative trials
      with randomized patients receiving clarithromycin or standard drugs identified
      equivalent clinical and bacteriologic outcomes. A higher rate of eradication of
      group A Streptococcus from the pharynx was achieved with clarithromycin than with
      penicillin VK. The potential advantages provided by high concentrations of
      clarithromycin in cells and tissues such as more rapid clinical improvement or
      shortened dosage schedules are still to be identified.

PMID- 8295818
TI  - Extent and spectrum of the antimicrobial activity of clarithromycin.
AB  - Clarithromycin, a new semisynthetic macrolide, is lipophilic and achieves
      concentrations in tissue that are generally 10 times greater than concentrations
      achieved in serum. Its binding to serum proteins is low and reversible.
      Clarithromycin has in vitro and in vivo activity against a variety of Gram
      positive and Gram-negative bacteria, Mycoplasma, Chlamydia and mycobacteria. 14
      Hydroxyclarithromycin, the major metabolite of clarithromycin in humans, is
      generally as active as clarithromycin against these organisms but is more active
      in vitro and in vivo than clarithromycin against Haemophilus influenzae.
      Organisms resistant to erythromycin by plasmid or transposon-encoded methylase,
      macrolide-lincosamide-streptogramin resistance, are also resistant to
      clarithromycin. Unlike older macrolides, however, clarithromycin has in vitro and
      in vivo activity against atypical mycobacteria. The antimicrobial activities of
      clarithromycin and 14-hydroxyclarithromycin are reviewed in this article.

PMID- 8295819
TI  - The 5q35bp chromosomal abnormality characterizes certain CD30 positive anaplastic
      large cell lymphomas offering a new definition of malignant histiocytosis in
      childhood.
AB  - Anaplastic large cell CD30 positive lymphomas represent a heterogeneous group of
      lymphomas in which immunocytochemical and molecular investigations have
      demonstrated the existence of malignancies of T, B or undetermined origin. The
      recent identification, in a few cases, of a chromosomal 5q35 breakpoint may allow
      distinction of a specific disease. In these cases, the 5q35bp has been found to
      be a permanent abnormality present in 5 cell lines and associated with various
      translocations including most often t(2;5) but also t(7;5), t(5;6) and t(3;5). A
      primitive myelomonocytic origin of these 5q35bp cells is suggested on the basis
      of the following arguments: i) they spontaneously express CD68; ii) they reduce
      tetrazolium blue; iii) they express the c-fms proto-oncogene which encodes the
      macrophage growth receptor (CSF-1); iv) c-fms, which is not rearranged, has been
      mapped to 5q33 close to the 5q35 breakpoint; v) treatment by phorbol-diester of a
      5q35bp cell line (DEL) induces immunodependent phagocytosis and modulation of the
      expression of c-fms, CSF-1 and TNF alpha. Since some 5q35bp cell lines also
      present rearrangements of TCR beta or Ig (jH), these data suggest an ancestral
      stem-cell origin, prior to T, B or myelomonocytic differentiation. Whatever its
      origin, the 5q35bp abnormality is mainly encountered in childhood malignancies.
      As it is constantly associated with the clinical and biological manifestations of
      a condition recognized by pediatricians as malignant histiocytosis, 5q35bp may
      today represent the best criterion for the identification of malignant
      histiocytosis in childhood.

PMID- 8295820
TI  - Contribution of platelet protein S (PS) to PS levels measured in plasma.
AB  - Protein S (PS) is a plasma protein synthesized by hepatocytes and endothelial
      cells and also found in platelets. Since it has previously been suggested that
      hereditary PS deficiency may sometimes remain undetected due to enhanced release
      of platelet PS into plasma, we investigated this question by measuring and
      comparing PS levels in plasma obtained using procedures susceptible to induce
      different degrees of platelet activation or disruption. Immunological and
      functional assays were employed. Plasma samples were obtained from blood
      centrifuged immediately on collection or after 3 h storage at room temperature,
      or following repeated freeze-thawing of platelet rich plasma. Analysis of
      variance revealed no significant difference in PS levels among the samples
      prepared by these different procedures. It is therefore doubtful that release of
      platelet PS content could mask a PS deficiency in plasma.

PMID- 8295821
TI  - The Arg-4 mutant factor IX Strasbourg 2 shows a delayed activation by factor XIa.
AB  - We have characterized at the DNA and protein levels a mutant factor IX, factor IX
      Strasbourg 2, which is responsible for a severe form (< 0.01 U/ml) of haemophilia
      B. Factor IX Strasbourg 2 has a higher molecular weight than normal factor IX. A
      mutation G-->A at position 6365 of the gene was demonstrated by DNA sequencing
      and confirmed by restriction mapping which showed absence of a Hae III site. This
      leads to the substitution of glutamine for arginine at position -4 of the
      propeptide. Factor IX Strasbourg 2 was purified from plasma by DEAE Sepharose
      chromatography and immunoaffinity and relative to normal factor IX, binding of
      calcium to the mutant protein was clearly reduced in calcium lactate agarose gel.
      Quantification of gamma-carboxyglutamic acid residues gave about 50%
      carboxylation as compared to normal factor IX. Microsequencing of the NH2
      terminal part of factor IX Strasbourg 2 confirmed the attachment of the
      propeptide and the mutation Arg-->Gln. Activation of factor IX Strasbourg 2 by
      purified factor XIa was found to be retarded as compared to normal factor IX, but
      after activation the mutant factor IXa was able to activate factor X. In
      conclusion, factor IX Strasbourg 2 circulates with the attached propeptide and
      shows reduced gamma-carboxylation and delayed activation by factor XIa but a
      normal capacity to activate factor X after total cleavage by factor XIa.

PMID- 8295822
TI  - Clinical studies on plasma protein C. Correlation with serum cholinesterase.
AB  - When compared to 32 healthy normal weight normolipidemic control subjects, plasma
      protein C antigen and serum cholinesterase activity were significantly decreased
      in 17 patients with decompensated cirrhosis of the liver and in 29 critically-ill
      surgical patients displaying the acute phase reaction, most of them without
      evidence of consumption coagulopathy. The low levels of these variables are
      considered to be subsequent to impaired and dysregulated hepatic protein
      synthesis. On the contrary, plasma protein C and serum cholinesterase were
      increased in 20 nephrotic patients and in 20 overweight hypertriglyceridemic
      subjects, a finding highly suggestive of enhanced hepatic synthesis probably
      related to an accelerated turnover of triglycerides. A discrepancy between low
      serum cholinesterase activity and normal or even high plasma protein C antigen
      was noted in 15 patients with cholestasis. This was particularly evident in 7
      subjects with extrahepatic cholestasis and an abnormal pattern of hepatic protein
      synthesis or impaired clearance of plasma protein C would appear to develop in
      such pathological conditions.

PMID- 8295823
TI  - Indications, procedure and results for the treatment of polycythaemia vera by
      bleeding, pipobroman and hydroxyurea.
AB  - The present report is based on an analysis of the evolution of 720 cases of
      Polycythaemia vera treated with pipobroman and 624 cases treated with
      hydroxyurea. General modes of treatment are identical for the two drugs,
      consisting of initial therapy at relatively high dose aimed at obtaining complete
      remission and maintenance therapy essential to conserve the improved clinical
      status. Both types of treatment must be adapted to suit the patient. Complete
      remission is achieved in 95 to 100% of cases with pipobroman and in 80 to 90% of
      cases with hydroxyurea. Incidents which may occur during initial therapy include
      cytopenia, more frequent and severe under treatment with hydroxyurea, rare
      transitory digestive troubles and cutaneous and mucous eruptions. Subject to
      control of the blood cell count every three to four months, maintenance therapy
      may be continued for many years and while the time lapse is as yet insufficient
      for hydroxyurea, resistance to pipobroman does not appear to develop even after
      more than 20 years of treatment. Although neither of these two drugs entirely
      avoids the occurrence of acute leukaemia which appears in 5 to 8% of subjects
      irrespective of the duration of therapy, on the contrary to observations in
      patients treated by bleeding alone, myeloid splenomegaly with myelofibrosis is
      rare and develops in no more than 2% of cases. The frequency of visceral cancers
      is not increased by either drug. Provided Polycythaemia vera is maintained in
      complete remission, thrombotic accidents occur no more often than in a normal
      population of the same age bracket.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295824
TI  - [The noninvasive determination of resting myocardial blood flow in patients using
      82 Rb in comparison with the argon method].
AB  - Resting myocardial blood flow in absolute units was determined in 11 patients
      without known heart disease using dynamic PET with 82Rb. Based on a modified
      Fick's approach to measuring myocardial blood flow, originally developed and
      validated in canine studies by Herrero and coworkers (Circulation 1990; 82: 1377
      86), a global flow value of 0.60 +/- 0.10 ml/min/gr myocardium (MV +/- SD, N =
      11) was obtained. With the exception of the apex, segmental blood flow was not
      significantly different in 12 left ventricular myocardial segments, indicating
      homogenous myocardial blood flow distribution. In 5 patients global myocardial
      blood flow was determined simultaneously both by 82Rb PET and argon as inert gas
      method. 82Rb flow did not differ significantly from argon flow (0.60 +/- 0.05 vs.
      0.68 +/- 0.15, MV +/- SD, N.S.). These results show that correct quantitation of
      resting myocardial blood flow with dynamic 82Rb PET is feasible also in patients.

PMID- 8295825
TI  - [Left ventricular function during symptomatic and asymptomatic myocardial
      ischemia].
AB  - Transluminal coronary angioplasty (PTCA) causes transient occlusion of the
      coronary artery and temporary ischemia of the left ventricle. Left ventricular
      dysfunction during silent and symptomatic episodes of myocardial ischemia during
      PTCA was evaluated continuously with a newly developed miniature, non-imaging
      scintillation probe. Parameters of left ventricular function were compared before
      and during balloon inflations of 60 s duration: ejection fraction (EF), indices
      of end-systolic and end-diastolic volumes (ESV, EDV), peak ejection and peak
      filling rates (PER, PFR). 13 patients (age 54 +/- 7.4 years) were symptomatic, 10
      patients (age 61 +/- 8 years) were asymptomatic. Impairment of left ventricular
      function during ischemia did not show any significant differences between the
      symptomatic and asymptomatic patients. It is therefore concluded that symptomatic
      and asymptomatic episodes of myocardial ischemia during PTCA cause similar
      impairment of systolic and diastolic left ventricular function. The degree of
      left ventricular dysfunction during PTCA cannot be estimated on the basis of
      clinical symptoms.

PMID- 8295826
TI  - Influence of blood viscosity on circulatory parameters determined by first-pass
      radionuclide angiocardiography in cor pulmonale.
AB  - First-pass radionuclide angiocardiography (FPRNA) with 99mTc-albumin was
      performed in 19 patients with cor pulmonale. Pulmonary circulation time (PCT),
      mean transit time (MTT), pulmonary stagnation index (PSI) were calculated from
      the time-activity curves for the estimation of cardiopulmonary circulation. Whole
      blood viscosity (WBV), plasma viscosity (PV) and hematocrit (HTC) were also
      measured on the same day. Significant prolongation of all parameters was observed
      (WBW: 5.04 +/- 1.19 mPas; PV: 1.36 +/- 0.17 mPas; HTC: 47.6 +/- 2.37%; PCT: 7.10
      +/- 2.15 s; MTT: 9.33 +/- 4.11 s; PSI: 1.30 +/- 0.37) in patients with cor
      pulmonale. Significant positive correlations were found between PCT and WBV (r =
      0.552; 0.001 < P < 0.01), MTT and WBV (r = 0.34; P < 0.05), furthermore between
      PCT and HTC (r = 0.356; P < 0.05). The results suggest that hemorheological
      parameters may influence the results of FPRNA, therefore, they should be
      determined in addition to the radionuclide study.

PMID- 8295827
TI  - Drug effects on cerebral blood flow in the baboon model--acetazolamide and
      nimodipine.
AB  - The sensitivity of the baboon model under anaesthesia for single photon emission
      computed tomography (SPECT) of the brain with 99mTc-HMPAO, as recently developed
      by us to study cerebral blood flow patterns, was investigated using drugs that
      are known to increase cerebral blood flow, e.g. acetazolamide, the carbonic
      anhydrase inhibitor and nimodipine, the calcium channel blocker. Increases in
      cerebral blood flow for both acetazolamide and nimodipine were observed that
      correspond well with other studies. Statistically significant regional
      specificity was noted for acetazolamide and nimodipine. Interestingly a
      combination of these drugs did not enhance cerebral blood flow but rather
      decreased it in comparison with the individual drug responses. The results were
      correlated with arterial blood pressure, heart rate, pCO2 and pO2. A blood
      pressure decrease was noted for both drugs, while acetazolamide had a marked
      influence on pO2. The results indicate that the baboon model is sensitive for
      evaluation of drug effects on cerebral blood flow.

PMID- 8295828
TI  - [Evaluation criteria for captopril-kidney function scintigraphy using 99mTc
      MAG3].
AB  - Renal function scintigraphy under ACE inhibition has gained an important role in
      the diagnosis of renovascular hypertension. Using the radiopharmaceutical 99mTc
      MAG3, 54 kidneys with angiographically verified renal artery status were
      evaluated with respect to the following scintigraphic parameters:
      intraparenchymal tracer transport, urine drainage, kidney size, and functional
      side-to-side ratio. In cases of decompensated renal artery stenosis, the typical
      scan finding using MAG3 was shown to be a distinct parenchymal nuclide retention
      in combination with a delayed appearance of the radiotracer in the pelvic system.
      In our patients, the visual impression of the renal sequential scans was superior
      to quantitative evaluation methods. Using these criteria in 43 patients with
      suspected renovascular hypertension, sensitivity and specificity were 89% and
      88%, respectively. Bilateral positive findings were nonspecific; when excluding
      them from the study, specificity increased to 100%.

PMID- 8295829
TI  - [Frequency and temporal occurrence of a functional autonomy in recurring goiter].
AB  - In 168 patients who underwent thyroid surgery due to a goitre the frequency and
      the temporal occurrence of functional autonomy in recurrent goitres were
      determined retrospectively. The diagnosis of functional autonomy was established
      by quantitative suppression scintigraphy with 99mTc. In the region examined the
      limiting value for functional autonomy is 1.0% 99mTcU after suppression. In 41%
      (n = 69) of the patients a recurrent goitre was found in the clinical
      examination. The postoperative observation period in this patient group ranged
      from 2 months to 42 years with an average of 13.8 years. Whereas the prevalence
      of functional autonomy in the early postoperative years was low, a continuous
      increase of thyroid autonomy with values of about 4% per year could be found
      until the 20th postoperative year, the rate of patients with functional autonomy
      was then about 70%. Thereafter the prevalence of thyroid autonomy increased only
      marginally and reached about 90% in the 40th postoperative year. The results
      demonstrate that functional autonomies in recurrent goitres are frequent. The
      majority of examined patients had recurrent and not residual autonomies.

PMID- 8295830
TI  - [Radioiodine therapy in Europe--a survey].
AB  - Treatment with 131I is a well known and widely accepted therapy for benign
      thyroid disease and thyroid cancer. High dose 131I therapy for ablative reasons
      in well-differentiated thyroid cancer is done mostly in hospitals with controlled
      area and adequate equipment for radiation protection. Low-dose therapies,
      however, of hyperthyroidism, thyroid autonomy and goiter may be done in out
      patients in many countries. Limits of radioactivity administered for an ambulant
      therapy are varying. In Germany, 131I therapy of out-patients is generally not
      permitted. As many patients are waiting for a therapy but capacity is too low,
      waiting lists up to several months exist. This leads to a kind of medical tourism
      into other countries where therapy of out-patients is possible. This is a crucial
      point with regard to optimal medical care as well to health economics. This paper
      presents the results of a questionnaire which was sent to the national EANM
      delegates of all European countries. There is a great variability among these
      countries which indicates the different views handling of radioactivity and
      radiation protection. A more detailed questionnaire about regulatory and
      administrative rules initiated by an EANM task group for risk assessment in
      nuclear medicine is on the way.

PMID- 8295831
TI  - [An incidental finding of a progressive diaphyseal dysplasia (Camurati-Engelmann
      syndrome)].
AB  - In a 35 year-old female diaphyseal hyperostosis of femur and tibia indicative of
      a Camurati-Engelmann syndrome (progressive diaphyseal dysplasia) were discovered
      during routine phlebography. This rare disorder belongs to the group of
      osteochondrodysplasias and affects primarily the diaphyses of long bones.
      Sporadic as well as familial cases have been observed. Although the cause and
      pathogenetic mechanism of the disease are unknown, an autosomal dominant
      inheritance is being discussed. Diagnosis was based on radiological findings,
      which are presented along with the scintigraphic appearance of the disease.

PMID- 8295832
TI  - [99mTc-MAA enrichment in the liver during a cavo-portal shunt over a recanalized
      umbilical vein].
AB  - Lung perfusion scintigraphy in a patient suffering from superior vena cava
      obstruction showed distinct MAA uptake in parts of the liver due to a collateral
      blood flow through abdominal parietal veins and a recanalized umbilical vein.
      Radiation therapy of mediastinal lymphomas was followed by a rapid decrease of
      caval portal shunt volume.

PMID- 8295833
TI  - Determinants of exercise and aerobic fitness in outpatients with arthritis.
AB  - Factors that influenced exercise behaviors and aerobic fitness were identified in
      100 outpatients with rheumatoid arthritis or osteoarthritis. Data included
      perceived health status, benefits of and barriers to exercise, and impact of
      arthritis on health; demographic and biologic characteristics; and past exercise
      behavior. Exercise measures included range-of-motion and strengthening exercises,
      7-day activity recall, and the exercise subscale of the Health-Promoting
      Lifestyle Profile. An aerobic fitness level was obtained on each subject by
      bicycle ergometer testing. The theoretical model predicted 20% of the variance in
      composite exercise scores but none of the variance in aerobic fitness levels.
      Perceived benefits of exercise was a significant predictor of exercise
      participation. Subjects with less formal education, longer duration of arthritis,
      and higher impact of arthritis scores perceived fewer benefits of exercise, while
      subjects who reported exercising in their youth perceived more benefits of
      exercise.

PMID- 8295834
TI  - Intestinal transit and body weight responses to ovarian hormones and dietary
      fiber in rats.
AB  - A two-part experimental design was used to study the effects of ovarian hormone
      cessation, hormone supplementation, and dietary fiber composition on body weight,
      appetite, and intestinal transit. In Part 1, effects of ovarian hormone status on
      body weight and baseline and stimulated intestinal transit were measured in chow
      fed rats. Sprague-Dawley rats were ovariectomized (OVX), then injected daily (22
      days) with estrogen (E), progesterone (P), the combination (E + P), or placebo.
      Controls were sham operated and placebo injected. Among OVX rats, E and E + P had
      the least body weight gain (9%, 6%); placebo and P had the greatest (36%, 34%).
      In OVX-P, baseline intestinal transit (measured in anesthetized rats as distance
      traveled by a charcoal marker) was relatively low, but vagal stimulation via
      centrally administered thyrotropin-releasing hormone evoked an increase
      significantly larger than that in other groups. In Part 2, experiments probed the
      interacting effects of ovarian hormone cessation and dietary fiber composition on
      body weight and baseline intestinal transit. Caloric intake was measured to
      determine the contribution of altered appetite. Rats were OVX or sham operated,
      then fed liquid diets with or without dietary fiber (25 days). OVX fiber-fed rats
      had significantly higher caloric intake, weight gain, and baseline intestinal
      transit than other groups. Caloric intake did not fully account for group
      differences. These results demonstrate modulation of GI function by ovarian
      hormones and dietary fiber.

PMID- 8295835
TI  - Differentiation of women with three perimenstrual symptom patterns.
AB  - The purpose of this study was to differentiate women with three perimenstrual
      symptom severity patterns: premenstrual syndrome (PMS), premenstrual
      magnification (PMM), and low symptom (LS). Factors entered into the discriminant
      functions included social demands, personal resources, socialization, parity,
      age, personal health practices, and psychological distress. A community-based
      sample of 142 women taking no oral contraceptives was classified into one of the
      three symptom severity patterns. Three two-way discriminant analyses were
      performed. Women with PMS had more psychological distress, more education, and a
      mother with more premenstrual symptoms than those with an LS pattern. Women with
      PMM had more psychological distress and a mother with more premenstrual symptoms,
      but they also had more stress and were younger than those with an LS pattern.
      Finally, the women with PMS, when compared to the PMM subgroup, were older, had
      more education, engaged in more positive health practices, and had more
      nontraditional attitudes toward women. In addition, the women with PMM had more
      stress in their lives than women with PMS.

PMID- 8295836
TI  - On fishing expeditions.

PMID- 8295837
TI  - Pain: its mediators and associated morbidity in critically ill cardiovascular
      surgical patients.
AB  - This study was conducted to determine the effects of age, sex, personality
      adjustment, and analgesic administration on the magnitude of pain experienced by
      74 cardiac and abdominal vascular surgical patients during their first few
      postoperative days. The relationship of pain magnitude to postoperative
      complications was also examined. Pain intensity was moderate and did not diminish
      over the first few postoperative days. Physical sensations and emotional tension
      associated with pain caused little distress. The primary consistent mediator of
      pain magnitude after surgery was the amount of analgesics administered to
      patients, although they received small amounts. Neither age nor personality
      adjustment influenced the magnitude of any pain dimension. However, women and
      patients having abdominal vascular surgery reported more disturbing physical
      sensations associated with their pain. Patients with greater pain intensity had a
      significantly greater incidence of atelectasis as a postoperative complication.

PMID- 8295838
TI  - Predictors of maternal role competence by risk status.
AB  - One hundred twenty-one high-risk women (HRW) and 182 low-risk women (LRW) were
      studied at postpartal hospitalization and at 1, 4, and 8 months after giving
      birth to determine whether they would differ in the achievement of perceived
      maternal competence and whether predictors of maternal competence would differ
      for the two groups over time. No significant differences were found in the
      maternal role competence of HRW and LRW or in the trajectory of change over time.
      Maternal role competence increased at 4 and 8 months over earlier levels.
      Selected variables explained from 33% to 52% of HRW's maternal competence and
      from 29% to 51% of LRW's maternal competence over the four test periods. Self
      esteem and mastery were consistent predictors of maternal competence for both
      groups. Fetal attachment was a predictor of competence among HRW only.

PMID- 8295839
TI  - Multidimensional predictors of success or failure with early weaning from
      mechanical ventilation after cardiac surgery.
AB  - The purpose of this study was to determine the contributions of pulmonary
      mechanics, gas exchange, and hemodynamic function to prediction of success or
      failure with early weaning from mechanical ventilation after cardiac surgery.
      More than 40 physiologic measurements were determined on 162 patients at two time
      points in the early postoperative period: during full-support mechanical
      ventilation and during a trial of spontaneous ventilation. Discriminant analysis
      was used to analyze the differences between the success group (n = 134) and the
      failure group (n = 28) and to predict group membership of individual cases. A
      moderately strong relationship (canonical correlation = 0.733) was found between
      the groups and the discriminating variables. The discriminant function contained
      variables from all three dimensions of weaning criteria, with dimensions of
      hemodynamic function and pulmonary mechanics having greater import. The predictor
      set had a sensitivity of .98, specificity of .71, positive predictive value of
      .94, and negative predictive value of .87. Routine bedside measurements had a
      predictive performance equal or superior to variables previously studied.

PMID- 8295840
TI  - Drug combinations and potential for risk of adverse drug reaction among community
      dwelling elderly.
AB  - Data were gathered through personal interviews from a sample of 667 people 65
      years of age and older, living in community settings and managing their own
      health. Almost two thirds of these older respondents reported at least one drug
      drug or drug-alcohol combination associated with a possible adverse reaction. The
      largest percentage of respondents were taking combinations of medications that
      could place them at risk for hypotension and cognitive impairment. These results
      suggest the need for more detailed screening of specific medications used by
      older people who report taking certain categories of drugs.

PMID- 8295841
TI  - Coping with unplanned childhood hospitalization: effects of informational
      interventions on mothers and children.
AB  - Two types of information, separately and in combination, were evaluated for their
      effects on the process and outcomes of maternal and child coping with unplanned
      childhood hospitalization. One hundred eight mothers of hospitalized children, 2
      to 5 years old, were randomly assigned to one of four study groups. Child
      behavioral information and parental role information had positive effects on
      maternal state anxiety as well as on parental support and participation in their
      children's care during hospitalization. Ten to 14 days following hospitalization,
      positive main effects were shown for child behavioral and parental role
      information on mothers' state anxiety levels and for child behavioral information
      on children's negative behaviors.

PMID- 8295842
TI  - Artifact management in pupillometry.
AB  - A detailed analysis of pupillometry data collection and handling procedures in
      the initial study uncovered a number of problems that threatened the integrity of
      the data, including improper procedures, lack of adherence to data collection
      rules, and inaccurate mathematical calculation of results. Substantial
      modifications in procedures were made to improve data collection and reduce
      artifact. With the increased sampling rate from 5 to 60 Hz and use of a videotape
      playback system, a more accurate and thorough method for removing artifact from
      pupillometry data was demonstrated in a subsequent study. The automated cleaning
      algorithm system proved to be efficient at detecting and removing artifact, as
      well as alerting users to artifact that might not be replaceable automatically.
      Additionally, this system provided another method of data storage, videotape,
      which was beneficial in reviewing the pupil behavior that was digitally recorded.
      Now that procedures for collecting pupil data and managing artifact have been
      objectively tested, steps can be taken towards establishing pupillometry as a
      reliable and valid screening tool for detecting excessive sleepiness.

PMID- 8295843
TI  - Milking data or meeting commitments: how many papers from one study?

PMID- 8295844
TI  - Pathophysiology and pharmacotherapy of common upper respiratory diseases.
AB  - The response of the upper respiratory tract to many environmental factors can be
      used both to analyze the body's inflammatory process and to choose appropriate
      therapy. The nose is the major pathway to the lungs, upper airways, sinuses,
      middle ears, and other parts of the body, and its reactions often represent a
      major portion of the problem. The most common upper respiratory illnesses are
      upper respiratory infections (URIs), primarily viral, followed by secondary
      bacterial infections. Approximately 20% of the total population may manifest
      allergic rhinitis, which is mediated by immunoglobulin E. This condition is often
      referred to as hay fever, although there is no direct allergy to hay, and there
      is no fever. The differential diagnosis includes nonallergic rhinitis with
      eosinophils, which mimics the pathophysiology of allergic rhinitis but yields
      negative results on skin testing; vasomotor and hormonal rhinitis; and rhinitis
      medicamentosa, the rebound congestion associated with overuse of topical
      adrenergic agents. Therapeutic options include avoiding causative agents,
      immunotherapy, and pharmacotherapy. Antihistamines produce excellent results in
      allergic rhinitis when sneezing and itching are present, but are of minimal value
      as decongestants. The alpha-adrenergic agonists are the optimum choices for
      congestion associated with viral URIs, and allergic or nonallergic rhinitis. Of
      major importance are accurate diagnosis, selection of appropriate therapy, and
      patient compliance.

PMID- 8295845
TI  - Effect of zinc or S-adenosyl-l-methionine on long term administration of low
      doses of lead to rats.
AB  - Two alternatives for the treatment of lead intoxication, administration of zinc
      or a thiol donor, S-adenosyl-L-methionine (SAM), were analysed. Rats were exposed
      to lead (Pb)-acetate (60 mg/l) in drinking water during 90 days; one group also
      received SO4Zn in water (40 mg/l), while another received both Pb and SAM (5
      mg/24 hr intraperitoneally. Erythrocytic delta-aminolaevulinic dehydratase (ALA
      D) activity was significantly reduced (P < 0.001) both in rats receiving Pb alone
      and in rats receiving Pb and each of the other two treatments. The high
      erythrocytic uroporphyrinogen synthetase (URO-S) activity noticed in Pb
      administered rats, was significantly (P < 0.001) reduced in animals treated
      either with zinc or with SAM. Hepatic ALA-D activity tended to decrease while
      renal enzyme activity was not modified by the low level Pb exposure used in this
      work. Interestingly, SAM treated rats in both tissues exhibited significantly (P
      < 0.01) higher activities of the enzyme. It is argued that SAM treatment causes a
      surplus of thiols that allows the full expression of ALA-D catalytic activity.

PMID- 8295846
TI  - Effects of dietary alpha-tocopherol and beta-carotene on lipid peroxidation
      induced by methyl mercuric chloride in mice.
AB  - Exposure of male CBA mice to methyl mercuric chloride, CH3HgCl, (10-40 mg/l in
      drinking water) for 2 weeks resulted in dose-related Hg deposition and enhanced
      lipid peroxidation in liver, kidney and brain. Mice were fed well-defined
      semisynthetic diets containing different levels of alpha-tocopherol (10, 100 or
      1000 mg/kg) or beta-carotene (1000, 10,000 or 100,000 IU/kg) for four weeks, two
      groups on each diet. The concentrations of alpha-tocopherol and beta-carotene
      used corresponded to deficient, normal and high levels. During the last two
      weeks, one group on each diet was given 40 mg CH3HgCl/l of drinking water. High
      dietary alpha-tocopherol protected against CH3HgCl induced hepatic lipid
      peroxidation, whereas the alpha-tocopherol deficient diet further enhanced
      CH3HgCl induced hepatic lipid peroxidation. Similar, though statistically non
      significant effects occurred in the kidneys, alpha-Tocopherol did not protect
      against CH3HgCl induced lipid peroxidation in the brain. Excess dietary beta
      carotene further enhanced CH3HgCl induced lipid peroxidation in liver, kidney and
      brain. CH3HgCl significantly decreased the activity of total glutathione
      peroxidase (T-GSH-Px) and Se-dependent glutathione peroxidase (Se-GSH-Px) in the
      kidneys in all dietary groups. High dietary alpha-tocopherol enhanced the
      activity of Se-GSH-Px in liver and kidney compared to the activity in mice fed
      the normal level of alpha-tocopherol. This occurred in mice exposed to CH3-HgCl
      as well as in unexposed mice, and the difference between CH3HgCl exposed and
      unexposed mice was not diminished. High dietary alpha-tocopherol increased the
      activity of both Se-GSH-Px and T-GSH-Px in the brain of CH3HgCl-exposed mice. The
      dietary level of beta-carotene did not affect the activity of the two enzymes in
      the organs investigated.

PMID- 8295847
TI  - Evidence for lysosomotropism of memantine in cultured human cells: cellular
      kinetics and effects of memantine on phospholipid content and composition,
      membrane fluidity and beta-adrenergic transmission.
AB  - Memantine, an amantadine derivative, is therapeutically used for the treatment of
      various neurological and psychiatric disorders such as Parkinson's disease,
      spasticity, and dementia. Pharmacokinetics of memantine and its effects on
      phospholipid content and composition, on membrane properties and functions such
      as fluidity and beta-adrenergic transmission were studied in cultured human
      fibroblasts and macrophages. The kinetic behaviour of memantine was
      characteristic for a lysosomotropic drug. Fibroblasts exposed to 14C-memantine in
      the microM range accumulated the drug up to 200 fold above initial medium
      concentrations. Lysosomal drug storage was proven by indirect evidence and by
      analyses of subcellular fractions. Repetitive exposure to memantine resulted in a
      cumulative uptake. While memantine uptake after single exposure was fully
      reversible, the rate and extent of release of chronically accumulated drug was
      reduced but could be enhanced by the addition of unlabelled memantine or ammonium
      chloride to the medium. Chronic, but not single, exposure to memantine above 10
      microM resulted in a concentration dependent phospholipid accumulation and in a
      shift in the phospholipid composition. There was an overproportionate increase in
      phosphatidylinositol at the expense of phosphatidylserine and sphingomyelin.
      Chronic exposure of cultured cells to memantine increased fluidity in the
      superficial layers of the plasma membrane and reduced the isoproterenol
      stimulated cAMP-response without affecting beta-adrenoceptor density. All these
      findings were compatible with the kinetic behaviour and the effectiveness
      expected of a weak lysosomotropic drug.

PMID- 8295848
TI  - Lipid peroxidation and antioxidant defense enzymes in various regions of adult
      rat brain after co-exposure to cadmium and ethanol.
AB  - Effect of cadmium (1 mg/kg body weight) and ethanol (2 g/kg body weight)
      exposure, alone as well as in combination, on essential trace metal homeostasis,
      lipid peroxidation and antioxidant defense enzymes in various regions of the
      adult rat brain was investigated. It was observed that cadmium when administered
      along with ethanol accumulated significantly in corpus striatum (3.5 fold) and
      cerebral cortex (3.0 fold) compared to the cadmium treated group. The ethanol
      induced accumulation of cadmium led to significant depletion in the levels of
      essential trace metals like zinc and copper in these regions of the brain.
      Further, cadmium or ethanol alone did not show any significant effect on lipid
      peroxidation and antioxidant defense enzymes in any of the regions of the adult
      brain but when given in combination, caused a significant increase in lipid
      peroxidation and markedly decreased the activities of antioxidant defense enzymes
      like glutathione peroxidase, superoxide dismutase and catalase particularly in
      corpus striatum and cerebral cortex. Structural alterations produced by increased
      lipid peroxidation after cadmium and ethanol co-exposure may have profound effect
      on the activities of membrane bound enzymes and hence may lead to functional
      impairment. The results of the present study imply that ethanol renders the adult
      brain more susceptible to the neurotoxic effects of cadmium. Corpus striatum and
      cerebral cortex are more vulnerable to the toxic effects of cadmium under the
      influence of ethanol than other regions of the brain.

PMID- 8295849
TI  - Inhibition of acetaminophen oxidation by cimetidine and the effects on
      glutathione and activated sulphate synthesis rates.
AB  - The aim of the present study was to examine the effects of the hepatotoxic drug,
      acetaminophen, on the synthesis rates of glutathione, activated sulphate (PAPS,
      adenosine 3'-phosphate 5'-phosphosulphate) and the acetaminophen metabolites,
      acetaminophen-glutathione and acetaminophen-sulphate after inhibition of
      cytochrome P-450 drug oxidation by cimetidine in isolated rat hepatocytes. The
      synthesis rates of glutathione and PAPS were determined simultaneously by an
      established method based on trapping of radioactivity (35S) in the prelabelled
      glutathione and PAPS pools. Preincubation of the hepatocytes with 60
      micrograms/ml cimetidine for 30 min. did not affect PAPS (1.71 versus 1.78
      nmol/10(6) cells) nor glutathione concentration (16.0 versus 16.4 nmol/10(6)
      cells). The subsequent incubation with 5 mM acetaminophen resulted in decreased
      PAPS synthesis in the cimetidine treated cells [0.79 x 10(3) versus 0.92 x 10(3)
      nmol/(10(6) cells.hr)] (P < 0.05). There was no difference in PAPS concentration
      or acetaminophen-sulphate synthesis [1.73 versus 1.79 nmol/10(6) cells and 13.0
      versus 12.9 nmol/(10(6) cells.hr), respectively]. Decreased PAPS synthesis may be
      related to decreased ATP supply or may be the result of a feed-back regulation
      due to diversion of sulphur from glutathione synthesis to sulfoxidation. The
      glutathione synthesis was not significantly affected by cimetidine treatment [57
      x 10(3) versus 27 x 10(3) nmol/(10(6) cells.hr)]. As expected acetaminophen
      glutathione synthesis decreased by 38% [1.66 versus 2.68 nmol/(10(6) cells.hr)]
      (P < 0.01). Also the glutathione concentration was lower in cimetidine treated
      cells [15.2 versus 15.9 nmol/10(6) cells] (P < 0.05). We have previously shown
      that glutathione synthesis was reduced if substrate availability decreased
      (acetaminophen concentration lowered).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295850
TI  - Localization of thermogenesis induced by single infusion of ephedrine in dog.
AB  - The localization of the thermogenic effect of ephedrine (1 mg.kg-1 infused
      intravenously over 10 min.) was studied in 6 fasted dogs anaesthetized with
      etorfin-acepromazin-N2O. Three experiments were performed in each animal to
      determine the effect of ephedrine on a) splanchnic oxygen uptake, b) lower leg
      oxygen uptake and c) the work of the heart. In all experiments whole body oxygen
      uptake was monitored. Following ephedrine administration the following
      significant changes were seen as whole body oxygen uptake increased 16%, and
      splanchnic and lower leg oxygen uptakes increased respectively from 38.4 to 42.3
      and from 7.3 to 12.1% of the whole body control oxygen uptake. The pressure
      volume work of the heart more than doubled. Significant changes were also seen in
      mean arterial blood pressure, pulse rate, cardiac output, splanchnic blood flow,
      and haematocrit and haemoglobin concentration. Plasma glycerol and free fatty
      acid concentrations increased after ephedrine, and the effects were not elicited
      by circulating catecholamines.

PMID- 8295851
TI  - Pharmacokinetic differences of desmethyldiazepam in three outbred Wistar strains
      related to differences in liver enzyme activities.
AB  - Various strains of rats differ in their sensitivities towards benzodiazepines
      suggesting that variations in biological features are responsible for these
      differences. All reports concern inbred strains. We have studied male rats of
      three outbred Wistar strains with regard to the pharmacokinetics of
      desmethyldiazepam given as a single intravenous dose. The elimination half-life
      of desmethyldiazepam was longer in the Riv:TOX(M) (from the National Institute of
      Public Health and Environmental Protection) and in the Cpb:WU strain than in the
      Crl:(WI)BR strain. This strain difference in elimination of desmethyldiazepam may
      be related to differences in liver enzyme activities.

PMID- 8295852
TI  - Inhibition of hepatic xenobiotic metabolism and of glutathione-dependent enzyme
      activities by zinc ethylene-bis-dithiocarbamate in the rabbit.
AB  - Effects of either a single (300 mg/kg) or a subchronic (0.3 and 0.6% for 70 days)
      oral administration of a dithiocarbamate fungicide (zinc ethylene-bis
      dithiocarbamate, zineb) on hepatic drug metabolism and on the activity of several
      glutathione-dependent enzymes were investigated in male New Zealand White
      rabbits. While a pronounced reduction in the rate of oxidative biotransformations
      occurred after either single or repeated exposure, both cytochrome P450 and total
      haem content were lowered following acute challenge to zineb. None of the
      experimental protocols affected microsomal carboxylesterase but induced a marked
      increase in glutathione content and none of the examined glutathione-dependent
      enzymes was altered by the single administration of zineb, whereas the
      subchronically exposed rabbits showed a fall in the activities of both total
      glutathione S-transferase and selenium-independent glutathione peroxidase. In the
      0.6% treated animals, a decrease in class mu glutathione S-transferase and
      glyoxalase I, and an increase in thiol-transferase activities were also recorded.
      It is concluded that (1) zineb is able to selectively impair oxidative drug
      metabolism with possible different mechanism(s) according to the duration of the
      exposure, (2) only the subchronic treatment affects glutathione-dependent
      enzymes, (3) the decrease in glutathione S-transferase activity would seem to be
      ascribed to a direct interaction with the fungicide.

PMID- 8295853
TI  - Altered behaviour in the progeny of rats exposed to ketamine, a N-methyl-D
      aspartate receptor blocker.

PMID- 8295854
TI  - [Inpatient psychological management in pediatric oncology: the concept of liaison
      management].
AB  - Concepts for counseling and long term support have been the major interest in the
      psychosocial care of pediatric oncology patients and their families. Similar
      methods for psychosocial care on the ward are still rare. This paper presents the
      psychological care of the oncology patients during their stay on the ward,
      complimentary to the medical treatment. The concept is based on the process of
      coping with the phases and specific situations (L.P.; B.M.A.; diagnosis;
      medication ect.) of the cancer therapy. This process contains on the part of the
      patients and their parents the need for information, active involvement in
      treatment regimes and relaxation (before, during and after the stressful
      situation). The concepts of informed consent, adherence and recovery-counseling
      are related to the coping methods of the patients and their parents. The aims of
      our concept are to create and utilize diagnostic tests and psychological methods
      to enable the families to help themselves. To reach this goal, the technique of
      semantic and pragmatic information is very important because this kind of social
      communication helps us to make the medical implications of the treatment
      understandable and suitable for the patients and families.

PMID- 8295855
TI  - [Role and responsibilities of the psychosocial patient care team in the pediatric
      clinic: (III) Review].
AB  - To prevent a possible fragmentation of professional networks, as described in
      part I, the psychosocial co-worker should be flexible to negotiate his or her
      role. Therefore part II described areas and problems of clinical engagement, and
      part III finally adds the scientific inquiry as another relevant task. Apart from
      gaining professional reputation, clinical studies may as well strengthen personal
      relationships among the professionals involved. The tendency of psychosocial
      specialists to isolate themselves is critically resumed with special regard to
      other psychosocial staff (clinic's kindergarten and school). This leads to a plea
      for a careful recognition of the competencies of all team members to assure that
      the positive effects of interdisciplinary cooperation will outweigh its possible
      negative side-effects.

PMID- 8295856
TI  - [The shame-blame-worry complex in parents of children after craniocerebral
      trauma].
AB  - The care complex of parents of brain damaged children represents a defense
      mechanism against the parents' shame-guilt-dilemma. The care complex does not
      meet with a coping behaviour being beneficial to the children, but demands rather
      too much of such children and adolescents. There is overprotection, a changed
      emotional acceptance of the child and a changed method of upbringing together
      with a strict control over achievements at school and therapies still necessary.
      Variants of the parents' subjective guilt with regard to the child are described
      in several case vignettes. Methods of the psychotherapeutic treatment of parents
      are discussed. Finally, an outlook in the consequences of the care complex as
      regards the self-image and self-acceptance in adolescence are given.

PMID- 8295857
TI  - [Promoting positive relations between parents and child--a counseling service for
      families with infants and young children in Sydney].
AB  - The "Early Intervention Programme" (EIP) in Sydney, Australia, is a home-based
      service for distressed families with children 0-3 years of age. It is funded as a
      child abuse prevention unit. The concept is based on the work of Selma Fraiberg
      (1980), who developed the first infant mental health program in Michigan, USA.
      The goal of the EIP is to strengthen the relationship between parents and child
      through developmental guidance, psychotherapy and/or provision of active help.
      The child is seen as an important partner in the intervention process.

PMID- 8295858
TI  - [Family counseling in separation and divorce in the court: the Regensburg model].

PMID- 8295859
TI  - Starchy legumes in human nutrition, health and culture.
AB  - Starchy legumes have been consumed by humans since the earliest practice of
      agriculture and have been ascribed medicinal and cultural as well as nutritional
      roles. They are an important component of the diet in the developing countries in
      Africa, Latin America, and Asia where they are especially valuable as a source of
      dietary protein to complement cereals, starchy roots and tubers. Legumes contain
      20-30% protein which is generally rich in lysine and limiting in sulfur amino
      acids. The nutritional quality of legume protein is limited by the presence of
      both heat labile and heat stable antinutrients as well as an inherent resistance
      to digestion of the major globulins. In addition to its nutritional impact,
      legume protein has been shown to reduce plasma low density lipoprotein when
      consumed. Legume starch is more slowly digested than starch from cereals and
      tubers and produces less abrupt changes in plasma glucose and insulin upon
      ingestion. Starchy legumes are also valuable sources of dietary fiber as well as
      thiamin and riboflavin. Starchy legumes are a valuable component of a prudent
      diet, but their consumption is constrained by low yields, the lack of convenient
      food applications, and flatulence.

PMID- 8295860
TI  - Development and quality evaluation of pawpaw-ogi.
AB  - Pawpaw-ogi was evaluated for proximate and chemical composition, amylograph
      pasting viscosity, colour and acceptability. The addition of pawpaw to maize ogi
      slurry had no significant effect on protein and fat contents nor on amylograph
      pasting characteristics but resulted in significant increases in ash, ascorbic
      acid, sugars and mineral contents. The Munsell colour notations indicated that
      the addition of pawpaw improved the colour of ogi. Taste panel evaluation showed
      that both the powder and porridge of pawpaw-ogi were acceptable.

PMID- 8295861
TI  - Effects of heat treatment and germination on trypsin and chymotrypsin inhibitory
      activities in sorghum (Sorghum bicolor (L.) Moench) seeds.
AB  - There was no appreciable change in proteinase inhibitory activity in sorghum upon
      dry heat treatment. However, moist heating reduced trypsin and chymotrypsin
      inhibitors to a greater degree. Germination (5 days) brought about complete
      reduction in proteinase inhibitory activity.

PMID- 8295862
TI  - Selected nutritional, physical and sensory characteristics of pan and flat breads
      prepared from composite flours containing fababean.
AB  - Composite flour blends containing wheat (W), fababean (F), cottonseed and sesame
      flours were formulated to provide the FAO/WHO/UNU protein requirements for the 2
      5 year old child, and evaluated in pan and flat bread applications. Water
      absorption of composite flour doughs was up to 35% greater than the control but
      gluten strength and slurry viscosities were markedly reduced. Loaf volume and
      specific volume of pan breads prepared from composite flours were 25-60% less
      than that of the control bread but flat breads tolerated the protein supplements
      extremely well. The W/F flat bread, containing 27% of fababean flour, received
      acceptable taste, texture and colour scores and was only slightly inferior to the
      control in puffing and layer separation. Additions of cottonseed or sesame flours
      to the W/F blend failed to improve sensory properties of the flat breads.

PMID- 8295863
TI  - In vitro bioavailability of iron from spinach (Spinacea oleracea) cultivated in
      soil fortified with graded levels of iron and zinc.
AB  - A pot-culture experiment was conducted to assess the bioavailability of iron from
      spinach cultivated in soil fortified with graded levels of iron and zinc (FeSO4 x
      7H2(0) and ZnSO4 x 7H2(0), respectively). Applications of varying levels of iron
      to soil increased the total iron and phosphorus contents and decreased the zinc
      content (P < 0.05). The effect of applying varying levels of zinc was the
      opposite of on the minerals in spinach. The ascorbic acid content was remarkably
      reduced with varying levels of iron and zinc. Higher levels of zinc and lower
      levels of iron in the soil increased the bioavailability of iron from spinach (P
      < 0.05). In conclusion, the interactions of 15 ppm zinc with 30 ppm iron
      significantly enhanced the bioavailability of iron, total iron and zinc contents.

PMID- 8295864
TI  - Production and chemical evaluation of some food condiments of Nigeria.
AB  - The study was aimed at investigating the nutrient and tannin composition of
      fermented legume seeds (oil bean, castor oil bean and African locust bean) used
      as food condiments in Nigeria. The legume seeds were purchased from local
      retailers, cleaned and subjected to varied fermentation periods. Standard assay
      techniques were adopted to analyze the parameters selected for use. The 4-day
      fermentation period caused the highest increases in protein and tannin and
      decreases in ash, lipids and non-protein nitrogen (NPN). The pulp of African
      locust bean had more protein an ash and the oil bean seeds less lipids and NPN.
      Fermentation times had varied effects on mineral levels. Fermentation for 4 d
      increased zinc, sodium and phosphorus except sodium for the African locust bean.
      The pulp had lower Zn and phosphorus than the seed. Fermentation for 4 d offers a
      greater advantage over other periods for production of nutritious and cheap food
      condiments in Nigeria.

PMID- 8295865
TI  - Nutrient composition and electrophoretic pattern of protein in two distinct types
      of phalsa (Grewia subinequalis DC).
AB  - Two distinct types, i.e. tall and dwarf types of phalsa, were studied for the
      differences in their physical parameters, chemical compositions and
      electrophoretic patterns of seed proteins by SDS-PAGE. The two types did not show
      any remarkable variation in their fruit weight, edible portion, seed weight and
      juice yield. Tall type had higher content of reducing sugars whereas total and
      non-reducing sugars were higher in drawf one. Qualitative analysis revealed the
      presence of sucrose and fructose in both the types whereas glucose was present
      only in tall one. Observed marked variations in the protein content of the fruit
      could be due to the differences in protein content of the seed rather than that
      of the pulp. Electrophoretic pattern of seed proteins revealed the complete
      absence of two protein bands of molecular weight 37, and 59 kD from the dwarf
      type.

PMID- 8295866
TI  - Alpha amylase inhibitors in sorghum (Sorghum bicolor).
AB  - Forty varieties of sorghum grown locally and four cereals were screened for
      inhibitory activity against human salivary amylase. Three varieties of sorghum
      (IS-22422, Nagi Monadi and Ngd Marnm) had maximum inhibitory activity of 124
      units. Among the cereals rice had the lowest inhibitory activity. Amylase
      inhibitory activity was lost on germination and heating the seeds.

PMID- 8295867
TI  - Effect of fermentation on the nutritional quality and functional properties of
      infant food formulations prepared from bambarra-groundnut, fluted-pumpkin and
      millet seeds.
AB  - Weaning foods were formulated by complementation of millet with bambarra
      groundnut seeds and fluted pumkin seeds. The proximate composition of the
      individual seeds and the formulations were determined. The composite flour blend
      containing the highest quantity of fluted pumkin seeds was found to have the
      highest protein and fat contents (24 and 8% respectively). Functional properties
      of formulated weaning foods were evaluated. The effect of fermentation on the
      nutritional quality of the products were determined by animal feeding
      experiments. The feed intake, weight gain and PER values were evaluated.
      Fermentation was found to improve the nutritional quality of the formulations.
      The fermented composite mixture of millet, bambarra groundnut and fluted pumpkin
      flour (1:1:2) was found to have the highest PER value of 2.1. This suggests that
      this fermented product will support growth in children better than other
      formulations.

PMID- 8295868
TI  - Effect of cutting, phosphorus and potassium fertilization on guar plant
      (Cyamoposis tetragonoloba) in newly reclaimed soil in Egypt.
AB  - A two year experiment was carried out in newly reclaimed soils (sandy soils) to
      investigate the effect of cutting and phosphorus and potassium fertilization on
      the growth, yield, seed mucilage content and seed protein content of guar plant.
      The results revealed that different cutting treatments significantly decreased
      the plant weight, seed yield, seed mucilage content and seed protein content.
      Phosphorus fertilization up to 350 kg super-phosphate (15% P2O5)/feddan*
      significantly increased plant weight, seed yield, seed mucilage content and seed
      protein content. Fertilization with 150 kg potassium sulfate (48% K2O)/feddan was
      quite capable to meet guar plant potassium demands in this kind of soil. Without
      cutting plants, fertilization with 350 kg super-phosphate and 150 kg potassium
      sulfate/feddan resulted in the highest seed yield, seed muculage content and seed
      protein content.

PMID- 8295869
TI  - The toxicants and phosphorus content of some Nigerian vegetables.
AB  - The oxalate, hydrocyanic acid, phytic acid and phosphorus contents of twelve
      leafy vegetables were determined. The values ranged from 47.7-194.3 mg/100 g DM,
      4.32-23.8 mg/100 g DM, 90-260 mg/100 g DM and 215-1110 mg/100 g DM, respectively.
      The ratio of phytic acid to phosphorus ranged from 13.9-90.7. The leaves
      contained low levels of hydrocyanic acid, while the oxalate, phytic acid and
      phosphorus contents were high. The results are discussed in terms of their
      clinical implications and nutritive values.

PMID- 8295870
TI  - Chemical composition and nutritional potential of the tribal pulse (Bauhinia
      malabarica Roxb).
AB  - Proximate and mineral composition, seed protein fractions, amino acid
      composition, fatty acid profiles and antinutritional factors were analysed for
      the seeds of the tribal pulse, Bauhinia malabarica. The seeds contained higher
      amount of crude lipid when compared with most of the domesticated pulses. The
      seeds were rich in minerals like Ca, Mg and Fe. Glutelins (45%) constituted the
      major seed protein fraction followed by globulins which accounted for about 34%.
      Cystine and methionine were found to be the limiting essential amino acids;
      whereas tyrosine and phenylalanine content were fairly high when compared with
      WHO requirement pattern. The unsaturated fatty acids, oleic acid and linoleic
      acid, were predominant in seed lipids. Presence of antinutritional substances
      like total free phenols, tannins, L-DOPA and haemagglutinating activity also were
      analysed/assayed.

PMID- 8295871
TI  - [Nitrogen-containing mycotoxins of fungi of Aspergillus and Penicillium species
      infesting grain and its products].
AB  - The review summarizes the literature data on distribution of nitrogen-containing
      mycotoxins (alkaloids) among Penicillium and Aspergillus fungi infesting grain
      and products of grain processing. Particular attention in given to clavins
      (ergotalkaloids) and tremorgens (roquefortine, verruculogen, penitrems).

PMID- 8295872
TI  - [Extracellular alkaline ribonucleases produced by Bacilli strains from the
      permafrost of the Kolyma lowland].
AB  - Aerobic spore-forming bacteria were isolated from the permafrost of the Kolyma
      lowland. Two strains of bacilli are shown to produce a relatively large amount of
      extracellular low-molecular weight alkaline RNases. The N-terminal amino acid
      sequences of the RNases secreted by these strains are similar. This suggests that
      the protein sequences of the RNases of Bacillus species have been conserved in
      the course of evolution.

PMID- 8295873
TI  - [Problems in the evaluation of predisposing factors to pulmonary tuberculosis].
AB  - Genetic predisposition is an important factor in pulmonary tuberculosis. The
      pattern of dermatoglyphic indicators is thought a reliable marker of such
      predisposition. Selective character of the disease emergence is related with an
      unfavorable combination of genetic and extra-genetic risk factors in an
      individual. A comprehensive assessment of the above factors may contribute to a
      reliable prediction of a high risk to develop tuberculosis.

PMID- 8295874
TI  - [Risk groups and morbidity of tuberculosis among outpatients of pediatric
      clinics].
AB  - The author's investigations demonstrate that children with somatic diseases
      registered for follow-up in pediatric outpatient departments should be referred
      to risk groups by tuberculosis. Special attention should be paid to children with
      a combination of gastrointestinal lesions with respiratory diseases.
      Phthisiologic risk in children with cardiovascular, skin affections and
      collagenoses is close to such in healthy subjects. It is recommended to use a
      differential approach to prophylactic measures in children followed up in
      outpatient departments and to prognosis of tuberculosis risk in them.

PMID- 8295875
TI  - [Clinical aspects and outcome of recurrent pulmonary tuberculosis].
AB  - Recurrent tuberculosis was treated in hospital in 86 patients, 82.7% of whom had
      destructive disease, while 84.0% disseminated the bacteria. Combined chemotherapy
      included 4 tuberculostatic drugs: 10% isoniazid (7 mg/kg iv drip), streptomycin
      (0.5 g intramuscularly), rifadin (0.6 g orally) and tisamid (25-30 mg/kg orally).
      The drugs were given twice a week under the intermittent regimen in combination
      with 10% isoniazid (7 mg/kg) and streptomycin (0.5 g) inhalations. During a mean
      hospital stay of 6.5 months disappearance of destruction and discontinuation of
      the bacilli dissemination were achieved in 91.1% and 93.9% of patients,
      respectively, suffering from infiltrative and disseminated tuberculosis.

PMID- 8295876
TI  - [Clinical aspects of pulmonary tuberculosis in patients with borderline disorders
      of carbohydrate metabolism].
AB  - Clinical symptoms and running of tuberculosis of the lungs were compared for
      matched patients with the presence of borderline disturbances of carbohydrate
      metabolism (group 1) or their absence (group 2). Group 1 patients were
      distinguished for more acute onset, severe intoxication, rapid development of
      advanced bilateral lesions with multiple destructions. Side effects in group 1
      were more frequent and chemotherapy results worse than in control group 2. It is
      emphasized that derangements of carbohydrate metabolism should be verified to
      make adequate corrections in treatment programs of tuberculosis.

PMID- 8295877
TI  - [Chemotherapy of destructive pulmonary tuberculosis with antioxidants and
      antihypoxic agents].
AB  - The trial included 155 patients with destructive pulmonary tuberculosis: 60 on
      conventional antibacterial therapy (isoniazid, rifampicin, streptomycin), 95 on
      intensive chemotherapy (isoniazid, rifampicin, streptomycin, pirazinamid or
      ethambutol, vitamins for initial 2-3 months). 69 patients from the latter group
      received adjuvant antioxidants (tocopherol acetate or galascorbin) in combination
      with one of the antihypoxants (piracetam, calcii pangamas, piriditol). The
      intensive chemotherapy promoted a decrease in duration of bacterial discharge,
      destruction discontimation, cavernous healing, reduced incidence rates of side
      effects. Metabolic processes characterizing lipid peroxidation and redox
      improved.

PMID- 8295878
TI  - [Tuberculosis in children and adolescents in orphanage and boarding schools and
      optimization of its prevention].
AB  - Clinical examinations and follow-up were conducted in 1641 children and
      adolescents at risk of tuberculosis infection. Of them, 701 examinees attended
      children's homes and boarding schools, 940 controls went to kindergartens and
      secondary schools. The trial revealed that the test group children and
      adolescents are at much higher risk to develop tuberculosis than controls.
      Primary infection and the disease were recorded in them 8.5 and 1.8 times more
      frequently, respectively. These facts urge compulsory introduction in children's
      homes and boarding schools as the foci of minor bacterial dissemination of the
      whole complex of antituberculosis measures, tuberculin diagnosis twice a year and
      isoniazid chemoprophylaxis, particularly.

PMID- 8295879
TI  - [Combined chemotherapy of patients with tuberculosis - new regimens and dosage
      forms].
AB  - 310 patients with pulmonary tuberculosis disseminating bacteria received
      isoniazid, rifampicin, streptomycin (ethambutol) and pirazinamid in different
      regimens and dosage forms. The drugs were administered in sequence or
      simultaneously, in single or divided doses. The best time and number
      characteristics as regards the discharge negativation were obtained in
      pirazinamid administration at a single dose daily or each other day irrespective
      of other drugs intake. 100 patients were given isoniazid, rifampicin and
      pirazinamid in multicomponent form tricox (Jemis, India). Tricox proved effective
      under additional administration of isoniazid in the same dose as was fixed in
      tricox.

PMID- 8295880
TI  - [Surgical treatment of patients with disseminated and progressing pulmonary
      tuberculosis].
AB  - The results of surgical treatment have been summarized for 97 patients with
      disseminated progressive and complicated tuberculosis associated with respiratory
      disorders. Of them, 89 (91.8%) had fibrous-cavernous disease and empyema, 72.2%
      exhibited bilateral advanced process. Noticeable disturbances of ventilation
      capacity were registered in 47 patients, grave ones in 22 cases. Restrictive and
      obstructive types predominated. External respiration was impaired most seriously
      when the process was disseminated and progressive. Respiratory failure increased
      with growing rates of the disease progression. Pulmonectomy was performed in 58,
      primary and staged trans-sternal transpericardial occlusions of the main bronchi
      in 25 cases. The effect was reached in 83.5%, 16.5% of patients died. Lethal
      outcomes occurred due to bronchopleural complications in 43.8%, pulmonary artery
      thromboembolism in 18.7% of surgical cases. It is inferred that pulmonary
      dysfunction cannot be a principal criterion for rejecting operative treatment in
      progressive and complicated pulmonary tuberculosis.

PMID- 8295881
TI  - [Treatment of renal and urethral tuberculosis (lecture)].

PMID- 8295882
TI  - [Combined tuberculin test in the diagnosis of female genital tuberculosis].

PMID- 8295883
TI  - [Correlation of dermatoglyphic and cellular immunity parameters in children with
      early stage of primary tuberculosis].
AB  - Immunological status and dermatoglyphic characteristics were compared in 55
      children aged 4-14 with a turn in tuberculin reactions. A correlation was
      established between genetic and immunological factors, this pointing to the fact
      that dermatoglyphics is a component of genotype indicative of natural resistance
      of children to tuberculosis. Synchronization between immunological and genetic
      values is less intensive in children with immunological disorders against those
      without them. The findings support the hypophysis on an evolutional role of M.
      tuberculosis as natural selection factors as well as setting up genetically
      determined mechanisms of natural resistance to tuberculosis.

PMID- 8295884
TI  - [Effect of HLA- genotype on bacterial colonization and antigenemia in patients
      with infiltrative pulmonary tuberculosis].
AB  - 150 patients with infiltrative tuberculosis (IT) and 135 healthy subjects were
      subjected to HLA-typing. Clinico-immunogenetic correlations provided evidence for
      significantly higher incidence of antigens A11, B12, Cw2, DR2, DR5 in IT patients
      versus healthy subjects. Antigens Cw3 and DR2 occur more frequently in
      progressive disease. IT patients disseminating M. tuberculosis carry more
      frequently antigens HLA-DR2, those with L-forms DR5, with antigenemia antigens
      HLA-DR2 and DR4.

PMID- 8295885
TI  - [Ultrastructural and radioautographic study of bronchoalveolar lavage cells in
      pulmonary tuberculosis in endobronchial laser therapy].
AB  - Seventy specimens of bronchoalveolar lavage were obtained from 30 patients with
      pulmonary tuberculosis during treatment with endobronchial laser. The lavage is
      shown to undergo marked qualitative and quantitative changes in response to He-Ne
      laser treatment: the proportion of macrophages goes up while that of neutrophils
      tends to a decrease. The laser is capable to induce metabolic and proliferative
      activity of alveolar macrophages indicated by RNA and DNA synthesis.
      Morphological alterations in the cells of the respiratory compartment suggest
      weakening of exudative-necrotic component of the inflammation as an underlying
      cause of laser efficacy.

PMID- 8295886
TI  - [Effectiveness of chemoprevention of tuberculosis in adolescents with
      hyperreactivity to the Mantoux test with 2 TU in tuberculin electrophoresis].
AB  - It is demonstrated that tuberculin electrophoresis in chemoprophylaxix for
      M.tuberculosis infection in adolescents with a marked of hyperergic reaction to
      the Mantoux test (2TU) contributes to enhancement of nonspecific immunological
      reactivity, to a decline in immunospecific reactions, and reduction in the
      response to the Mantoux test (2TU).

PMID- 8295887
TI  - [Effect of Mycobacterium tuberculosis on activity of lysosomal enzymes in mouse
      peritoneal macrophages].
AB  - The studies of the effects produced by M. tuberculosis various strains on the
      activity of lysosomal enzymes in peritoneal mouse macrophages demonstrated
      multidirectional influence of the bacilli. Non-sedimentary activity rose in
      matrical enzymes indicating lysosomal membranes instability due to M.
      tuberculosis infection followed by hydrolase activation and hydrolases escape
      into the cytosol. An inhibiting action of pathogenic mycobacteria on lysosomal
      proteases is suggested.

PMID- 8295888
TI  - [Cellular reactions in contamination with various types of Mycobacterium in
      experimental study].
AB  - Characteristics of specific inflammation induced by intradental challenge with
      mycobacteria (MB) were studied cytologically and bacterioscopically.
      Mycobacterium tuberculosis hominis and bovis, BCG, atypical M. fortuitum in the
      5th dilution by turbidity standard were administered into the root canals of a
      tooth and pulp cavities of 16 mongrel dogs (body mass 13-16 kg, age 1-4 years).
      Investigation of the dogs' organs and paradental tissues revealed that MB
      underwent L-transformation the speed of which depended on the species. Cellular
      reactions were also related to the agent species and form of vegetation.
      Cytobacterioscopic tests are proposed as additional diagnostic means and to
      validate therapeutic policy.

PMID- 8295889
TI  - [Evaluation of pulmonary tuberculosis activity by polarization microscopy of
      liquid crystals].

PMID- 8295890
TI  - [Clinical manifestation of tuberculous exudative pleuritis in children and
      difficulties in its diagnosis].

PMID- 8295891
TI  - [Rare case of Park's-Weber disease simulating infiltrative pulmonary
      tuberculosis].

PMID- 8295892
TI  - [Aging, antituberculosis immunity, immunotherapy (review literature)].

PMID- 8295893
TI  - [Leukotrienes and their role in lung pathology (review literature)].

PMID- 8295894
TI  - [Ivan Timofeevich Stukalo (birth centenary)].

PMID- 8295895
TI  - [Modified screening of lung diseases in industrial workers].
AB  - The paper summarizes the results obtained at examination of industrial workers
      using a modified screening. This included questionnaires, oriented general
      examination, evaluation of external respiration with its monitoring during
      working hours. Such approach proved informative and provided a sufficient symptom
      complex to make diagnosis of occupational asthma.

PMID- 8295896
TI  - Establishment and survival of the strobilar stage of Taenia crassiceps in
      hamsters, gerbils, and mice, with reference to different helminth isolates.
AB  - Following the oral administration of metacestodes of two isolates of Taenia
      crassiceps, the enteral establishment and survival of the strobilar stage were
      examined in golden hamsters (Mesocricetus auratus), Mongolian gerbils (Meriones
      unguiculatus) and laboratory mice. The origin of the isolates was Microtus
      montebelli caught in Japan in 1985 or Clethrionomys rutilus captured on St.
      Lawrence Island, Bering Sea, in 1988 (abbreviated as JPN and SLI isolates),
      respectively. The enteral establishment of the SLI isolate was distinctly higher
      than that of the JPN isolate in golden hamsters and mice, whereas the difference
      was marginal in Mongolian gerbils. All initially-established parasites survived
      to become gravid adults in prednisolone-treated golden hamsters and Mongolian
      gerbils; the average recovery of cestodes of the SLI and JPN isolates were 55.8%
      76.7% vs 11.7%-35.0% in the former and 28.0%-52.7% vs 25.8%-32.2% in the latter.
      The distinctly higher level of enteral establishment of the SLI isolate in golden
      hamsters makes available a model for quantitative studies on parasite-host
      relationships in experimental taeniasis.

PMID- 8295897
TI  - Severe pulmonary pneumocystosis in simian acquired immunodeficiency syndrome
      induced by simian immunodeficiency virus: its characterization by the polymerase
      chain-reaction method and failure of experimental transmission to immunodeficient
      animals.
AB  - Pneumocystis carinii (Pc) infection was observed in three of five rhesus monkeys
      infected with simian immunodeficiency virus (SIVmac251). They showed severe
      symptoms similar to those associated with human acquired immunodeficiency
      syndrome (AIDS). Histopathology revealed severe pulmonary pneumocystosis in one
      of three Pc-positive monkeys, and anti-Pc antibodies were detected in sera from
      two of the three monkeys. Localization of Pc organisms in various organs of the
      monkeys was examined by the polymerase-chain-reaction (PCR) method, and Pc
      specific bands of DNA amplification were detected in the liver, kidney, spleen,
      adrenal gland, testis, brain, and other organs examined, but no Pc organism was
      found in these organs by histopathologic examination. These results suggest that
      the activation of a latent infection of Pc occurs in SIV-infected rhesus monkeys
      as well as in human AIDS. Experimental transmission of Pc derived from a simian
      was attempted in severe combined immunodeficiency (SCID) mice and athymic nude
      (rnu/rnu, F344) rats. These animals were inoculated intranasally with 10(4) Pc
      cysts, but neither histopathologic changes nor Pc organisms were detected in SCID
      mice at 4 months after inoculation or in nude rats at 2 months postinoculation,
      suggesting that simian Pc is species-specific.

PMID- 8295898
TI  - Lymphocyte response in vitro to Plasmodium falciparum merozoite antigens in
      donors from a holoendemic area.
AB  - Crude merozoite antigens from Plasmodium falciparum were used to evaluate the
      proliferative response of peripheral mononuclear cells (PBMCs) from 114
      inhabitants of the village of Dielmo (Senegal, West Africa) exposed continuously
      to malaria transmission. The high or low responses to merozoite antigens obtained
      in lymphocyte stimulation assays were correlated with the presence or absence of
      parasites, IFN-gamma production and HLA phenotype. The high responders produced
      high levels of IFN-gamma, in contrast to the low responders, most of whom did not
      secrete IFN-gamma (23/27). Among others, the two HLA phenotypes HLA-B51 and HLA
      DR1 were significantly associated with a high response (P < 0.05).

PMID- 8295899
TI  - The metabolism of arachidonic acid to prostaglandin E2 in plerocercoids of
      Spirometra erinacei.
AB  - With a simplified method of extracting and purifying prostaglandins, trace
      prostaglandins (nanogram order) were detected by gas chromatography-mass
      spectrometry. Arachidonic acid was metabolized to prostaglandin E2 (PGE2) by
      plerocercoids of Spirometra erinacei, the PGE2 was detected in the medium after
      incubation with arachidonic acid, and the role of albumin in the absorption of
      free arachidonic acid by plerocercoids and in the release of its metabolite was
      investigated. Plerocercoids absorbed arachidonic acid-binding albumin and
      released PGE2 efficiently. PGE2 is known to suppress the functions of mononuclear
      cells of the host. The selective release of PGE2 may be related to the escape
      mechanism of plerocercoids of S. erinacei from the host immune system to become
      established larva migrans, i.e., sparganosis.

PMID- 8295900
TI  - Protein characterization of Babesia equi piroplasms isolated from infected horse
      erythrocytes.
AB  - Proteins of Babesia equi piroplasms were characterized. The piroplasms of B. equi
      were purified by lysis of infected horse erythrocytes with N2 gas cavitation
      followed by separation in Percoll density-gradient centrifugation. The relative
      molecular weights (Mr) of major proteins separated by two-dimensional sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis were 18, 28, 30, 41, 43, 54,
      66.5, and 96 kDa. Immunoblot analysis using serum from an experimentally infected
      horse revealed six immunodominant proteins of 15, 18, 28, 30, 41, and 96 kDa. Two
      immunodominant proteins of 18 and 28 kDa were membrane-bound proteins as revealed
      by Triton X-114 phase partitioning.

PMID- 8295901
TI  - In vitro synthesized immunoglobulin A from nu/+ and reconstituted nu/nu mice
      against a dominant surface antigen of Giardia lamblia.
AB  - Nu/+ mice (ZU.ICR-strain) experimentally infected with Giardia lamblia (clone
      GS/M-83-H7) cleared the infection by day 45 postinfection (p.i.). Athymic nu/nu
      mice were reconstituted with immune Peyer's patch lymphocytes obtained from self
      healed nu/+ littermates and thus acquired the potential to decrease their
      intestinal parasite mass. Intestinal B-cells from self-healed nu/+ mice as well
      as from immune-reconstituted athymic nude mice synthesized in vitro parasite
      specific immunoglobulin A (IgA). This IgA was subsequently analyzed by
      immunoblotting, showing a predominant reaction with the major surface antigen (a
      72,000-Da polypeptide) characterizing the Giardia clone in question. The
      hypothesis on the causative role of intestinal IgA and immune lymphocytes in the
      control of G. lamblia infection thus deserves further attention.

PMID- 8295902
TI  - Biochemical and functional characterization of histone H1-like proteins in
      procyclic Trypanosoma brucei brucei.
AB  - Four variants and/or posttranslational modifications of histone H1-like proteins
      of Trypanosoma brucei brucei procyclic culture forms were extracted with 0.25 N
      HCl from isolated nuclei and analyzed by two-dimensional gel electrophoresis. The
      amino acid composition of these proteins, their ability to space nucleosomes
      regularly and to induce salt-dependent condensation of the chromatin indicated
      their histone H1 nature. On the other hand, the histone H1-like proteins clearly
      differed from their higher-eukaryote counterparts by their weak interaction with
      DNA under low-salt conditions. As a consequence, intact nucleosome filaments were
      prepared according to a new preparation protocol especially adapted to the
      unstable chromatin of T. b. brucei. Our results indicate that the biochemical
      properties of the histone H1-like proteins contribute to the structural and
      functional differences between the chromatin of procyclic T. b. brucei and that
      of higher eukaryotes.

PMID- 8295903
TI  - Paramyosin of Echinococcus granulosus: cDNA sequence and characterization of a
      tegumental antigen.
AB  - A lambda ZAPII cDNA library of Echinococcus granulosus larvae was expressed in
      Escherichia coli SURE cells. Screening of the library with a rabbit antiserum
      raised against total larval antigen yielded several immunoreactive clones. For
      analysis of the nucleotide sequence, in vivo excision into pBlueskript was
      carried out and the 3' end of the cloned insert was sequenced. Three of these
      clones exhibited identical nucleotide sequences, suggesting expression of
      identical genes. The complete nucleotide sequence of the largest clone, EG36,
      with a 3.4-kb insert was determined, presenting an open reading frame of 2.59 kb.
      The predicted amino acid sequence showed 71.4% identity to the Schistosoma
      mansoni paramyosin and a significant homology to a 17 amino-acid peptide sequence
      from antigen B of Taenia solium. From these data we conclude that EG36 is the
      paramyosin of E. granulosus. For protein purification, the coding sequence of the
      cDNA was amplified by polymerase chain reaction and ligated in frame into the
      expression vector pGEX-3X. Affinity-chromatography-purified GST fusion protein
      was used to induce a polyclonal rabbit antiserum. Immunoblot analysis revealed
      the expression of a 97-kDa protein by the E. coli clone and that of a protein
      with a similar molecular weight in protoscolices from E. granulosus and E.
      multilocularis as well as in E. granulosus cyst fluid. Immunofluorescence studies
      showed that EG36 was localized throughout the tegument of E. granulosus and E.
      multilocularis larvae. Sera from patients suffering from echinococcosis,
      schistosomiasis, and neurocysticercosis reacted with the purified fusion protein
      when tested in an enzyme-linked immunosorbent assay.

PMID- 8295904
TI  - Treatment of fish parasites. 11. Morphogenesis of Henneguya laterocapsulata
      Landsberg, 1987 (Myxosporea, Myxozoa), and the effects of a new triazine
      derivative, HOE 092 V, on its developmental stages: a light and electron
      microscopy study.
AB  - The ultrastructure of sporogenesis was studied in Henneguya laterocapsulata
      parasitizing the skin of hybrid catfish (Clarias gariepinus x Heterobranchus
      bidorsalis) in Nigeria. Sporogenesis started when a generative cell was
      surrounded by a second nondividing cell (i.e., envelope cell). By subsequent
      divisions of the generative cell, ten cells were produced, which finally became
      arranged into two spore-producing units. Each unit consisted of a binucleate
      sporoplasm, two capsulogenic cells, and two valvogenic cells. Apparently
      capsulogenesis, valvogenesis, and sporoplasm differentiation occurred
      concomitantly. In research for chemotherapy of fish parasitized by myxosporeans a
      new triazine derivative, 2-[3,5-alpha-dichloro-4-(4-methyl-sulfonylphenoxy)
      phenyl]-1-me thy l- hexahydro-1,2,4-triazine-3,5-dion (HOE 092 V), was tested in
      vivo against the uni- and multicellular developmental stages of H.
      laterocapsulata. Naturally infected catfish were incubated in water containing 0,
      2.5, 5, and 10 micrograms HOE 092 V/ml or the pure solvent for 3 h. After the
      fish had been returned into fresh water, they were killed 1 day after the
      treatment and the plasmodia were studied by means of light and transmission
      electron microscopy. Starting with a dose of 2.5 micrograms HOE 092 V/ml, the
      pericyte's outer membrane was broken in the bi- and multicellular stages. The
      number of ribosomes in the bi- and multicellular stages decreased. In the
      multicellular stages the rough endoplasmic reticula of the capsulogenic cells
      were enlarged. Treatment with 5 micrograms HOE 092 V/ml led to breaks in the
      limiting outer membranes of the capsulogenic cells and to vacuolization of their
      peripheral cytoplasm. In early prespore stages a decrease in the number of
      spherical inclusions was recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295905
TI  - Structural and cytochemical study of the hemocytes in normal and trematode
      infected Lymnaea truncatula.
AB  - The ultrastructural study of adult Lymnaea truncatula hemocytes reveals a
      preponderance of spreading cells at different stages of differentiation. A few
      round cells may represent a distinct population of hemocytes. As in L. stagnalis,
      spreading cells are remarkable in that they synthesize peroxidase that is stored
      in secretory granules, but in L. truncatula hemocytes, endogenous peroxidase
      activity is also localized in multivesicular bodies. The ultrastructure and
      peroxidase content of hemocytes do not seem to be affected in snails with
      established parasites. Evidence that parasites interfere with normal hemocyte
      functions is that in the few capsules that occurred in parasitized snails the
      hemocytes did not spread normally and their peroxidase granules were resorbed
      into multivesicular bodies.

PMID- 8295906
TI  - Characterization of sinefungin-resistant Leishmania donovani promastigotes.
AB  - Promastigotes resistant to sinefungin (SF), a nucleoside antibiotic that is
      structurally related to S-adenosylmethionine (AdoMet), were obtained starting
      from two cloned strains of Leishmania donovani. The resistance was induced by
      increasing the drug pressure gradually until promastigotes capable of growing in
      the presence of concentrations 10,000 times higher than the 50% growth-inhibitory
      (IC50) values for the control cells were obtained. The resistance to SF of both
      clones was specific and stable in the absence of drug pressure. High-performance
      liquid chromatographic (HPLC) analyses indicated highly reduced levels of SF in
      the two resistant clones. However, the intracellular SF concentration in these
      resistant cells was much higher than the IC50 values for wild-type cells. In one
      clone, the decreased drug uptake was coupled to a decrease in the affinity of two
      protein methylases for SF, whereas in the other clone the biosynthesis of
      polyamine precursors was modified. This study demonstrates that resistance to a
      drug molecule with pleiotropic targets can be developed through various
      mechanisms by different strains.

PMID- 8295907
TI  - Neuropeptide F-immunoreactivity in the tetrathyridium of Mesocestoides corti
      (Cestoda: Cyclophyllidea).
AB  - The distribution pattern and subcellular localisation of neuropeptide F (NPF)
      immunoreactivity (IR) in the tetrathyridium stage of Mesocestoides corti were
      investigated by whole-mount immunocytochemistry in conjunction with confocal
      scanning laser microscopy (CSLM) and by immunoelectron microscopy using
      immunogold labeling. Using an antiserum directed to the C-terminal decapeptide
      amide (residues 30-39) of synthetic NPF (Moniezia expansa), CSLM revealed NPF-IR
      throughout the central and peripheral nervous systems of parental and dividing
      tetrathyridia. Ultrastructurally, gold labeling of NPF-IR was confined to the
      contents of the smaller of the two sizes of electron-dense neuronal vesicle
      identified.

PMID- 8295908
TI  - Biochemical markers of pathogenicity and virulence of Acanthamoeba sp. strains.
AB  - The aim of our study was to demonstrate a possible correlation between some
      biochemical and biological markers of the degree of virulence of the investigated
      strains of Acanthamoeba sp. The results obtained demonstrated a significant
      correlation between the activity of proteases, peroxidases, and superoxide
      dismutase and the degree of virulence of the strains as previously defined by
      tests on mice. The results also proved that the strains that killed some of the
      infected mice were characterized by the highest value recorded for the activity
      of peroxidase and the lowest value obtained for the activity of superoxide
      dismutase.

PMID- 8295909
TI  - High-performance liquid chromatographic analysis of monoamines in the cestode
      Diphyllobothrium dendriticum.
AB  - The presence of biogene monoamines in adult and larval Diphyllobothrium
      dendriticum (Cestoda) was investigated by high-performance liquid chromatography
      with electrochemical detection (HPLC-ED). The biogene amines serotonin (5-HT),
      dopamine (DA), noradrenaline (NA), and adrenaline (A) as well as many of their
      precursors and metabolites, comprising a total of 15 different substances, were
      analyzed. 5-HT, DOPA, DA, NA, and A were detected in the worm, with 5-HT, DOPA,
      and DA being the dominating amines. The DA metabolites DOPAC and 3-MT or the 5-HT
      precursor 5-hydroxytryptophan could not be detected, but two unidentified
      substances, believed to be catecholic, were present in the worm. A high
      concentration of DOPA was measured in the proglottids and especially in the eggs.
      This is the first report of A in a flatworm.

PMID- 8295910
TI  - Synthesis, anticonvulsant and antimicrobial activities of certain new
      furochromones.
AB  - Some new substituted thiazolidinones, thioimidazolidinones and thiazolines have
      been synthesized from N1-substituted N2-(4-hydroxy-7-methyl-5H-furo[3,2-g]
      [1]benzopyran-5-on-9-yl)thioureas and monochloroacetic acid or alpha-halocarbonyl
      compounds. Some representative examples were tested for their anticonvulsant and
      antimicrobial activities.

PMID- 8295911
TI  - 2,4-Dimethyl-6 H-pyrido[3,2-b]carbazole, an isomer of the antitumor alkaloid
      ellipticine via the Combes-Beyer reaction.
AB  - The synthesis of 2,4-dimethyl-6 H-pyrido[3,2-b]carbazole (2a) and of its 9
      methoxy (2b) and 9-hydroxy (2c) derivatives via the Combes-Beyer reaction is
      described. Pyridocarbazole 2a has been obtained by two different routes. In the
      course of the synthesis of 2b either a partial or a total demethoxylation has
      been observed depending on the route employed.

PMID- 8295912
TI  - [Stability and new formulations of hexetidine. 2. Formulations and in vitro
      bioavailability].
AB  - The solubilization of the water insoluble antimicrobial compound hexetidine is
      achieved by tensides and cyclodextrins. Using tensides the active ingredient is
      associated with the lipophilic part of the emulsifier. Tensides with a
      hydrophilic element in the lipophilic part of the molecule show better
      solubilizing properties. In contrast a higher stability is achieved with
      emulsifiers without hydrophilic elements in the lipophilic part of the molecule.
      The antimicrobial activity, determined by an in vitro test, is not influenced by
      the type of emulsifier. Cyclodextrins form inclusion complexes with hexetidine.
      Hydroxy propyl-beta-cyclodextrin is preferred due to its high water solubility.
      This inclusion complex shows compared with tenside solubilization a better taste
      and stability. The in vitro antimicrobial activity was comparable to tenside
      solubilized products.

PMID- 8295913
TI  - [The biotransformation of the anticonvulsant 4-p-chlorophenylpyrrol-3-morpholino
      2-carboxylic acid methyl ester (AWD 140-076)].
AB  - 4-p-Chlorphenylpyrrole-3-morpholino-2-carboxylic acid methylester (1; AWD 140
      076) is a substance with anticonvulsive properties. After p.o. administration in
      male wistar rats many metabolites in relatively small concentration are excreted
      in urine and faeces, six of them could be isolated and identified as quantitative
      dominating compounds. Compound 1 is attacked in different sites of the molecule
      by the cytochrome P-450 system. At the morphine ring N- and O-dealkylation
      reactions take place leading to the cleavage of the ring. After that a stepwise
      degradation by oxidative and reductive processes occurs. Further reactions
      concern the N-oxidation of the morpholine nitrogen as well as the hydroxylation
      of the pyrrole skeleton forming the main metabolites. 5 metabolites are also
      present as sulfate or glucuronide conjugates. The quantity ratio of the phase I
      to phase II metabolites amounts to 9:1. In the in vitro test system isolated
      perfused rat liver and rat hepatocytes culture solely the two main metabolites
      are formed. Compound 1 is characterized by enzyme inducing activities. The
      oxidative demethylation of p-nitroanisole is increased 4-fold after pretreatment.

PMID- 8295914
TI  - Vermiculin derivatives. Part 2: Cytotoxic and mutagenic activities of vermiculin
      derivatives.
AB  - The induction of mutations at the HPRT locus and cytotoxicities of 4 vermiculin
      derivatives 2-4 and 6 were examined in V79 Chinese hamster cells and compared
      with those of the parent compound vermiculin (1). Derivatives prepared by
      hydrogenation were less toxic and mutagenic or non toxic and non mutagenic. The
      substitution at position 13 affected the evaluated biological effects. The
      results suggest that in vitro metabolism of vermiculin resulted in decreased
      cytotoxicity and mutagenicity.

PMID- 8295915
TI  - Synthesis and physicochemical study (pka, logP) of some new thiazole derivatives
      with probable local anaesthetic activity.

PMID- 8295916
TI  - [Synthesis, properties, and biological activity of some substituted 2'-, 3-, 3'-,
      4- and 4'-azachalcones].

PMID- 8295917
TI  - Synthesis and in vitro activity of new cephem derivatives with benzoxazolone
      ring.

PMID- 8295918
TI  - Synthesis and biological activity of some N1-substituted orotic acids.

PMID- 8295919
TI  - [Preparation and properties of some derivatives of 2-, 3-, and 4-(2-hydroxy-3
      amino-propoxy)-2',3'- and 4-azachalcones].

PMID- 8295920
TI  - [In vivo penetration of isosorbide dinitrate from a transdermal therapeutic
      system in rat skin].

PMID- 8295921
TI  - Biological activities of some 3,4-disubstituted-1,2,4-oxa(thia)-diazole-5(4H)
      ones(thiones).

PMID- 8295922
TI  - The mushroom Pleurotus ostraetus exhibits OH radical scavenging activity.

PMID- 8295923
TI  - The phonetic interpretation of tone in Igbo.
AB  - This article presents a preliminary study of the phonetic interpretation of tone
      in Igbo, a Kwa language of southeastern Nigeria. The experimental method varies
      the speaker's pitch range orthogonally with variation in tonal material, and fits
      a model to measurements of maxima and minima in the resulting F0 contour. A new
      interpretation of downstep is proposed as a result.

PMID- 8295924
TI  - Effects of time pressure on the phonetic realization of the Dutch accent-lending
      pitch rise and fall.
AB  - The goal of this experiment is to find the most important phonetic features of
      Dutch accent-lending pitch movements, in terms of shape, pitch level and
      alignment with the segmental structure. Time pressure is used as a heuristic
      method to isolate important phonetic aspects of pitch movements, assuming that
      under time pressure the speaker will preserve those aspects. In a production
      experiment, accent-lending rises ('1') and falls ('A') were realized under
      various types of time pressure. The pitch rise is time-compressed under all
      pressure types, which would mean that the shape of the rise is relatively
      unimportant. The segmental alignment of the rise proved to be more important: the
      onset of the rise is synchronized with the syllable onset. For the fall no fixed
      synchronization point was found, but its shape was relatively invariant,
      indicating that shape rather than exact timing is the more important feature of
      the fall.

PMID- 8295925
TI  - Intonation of clause-internal filled pauses.
AB  - Clause-internal filled pauses and preceding peak fundamental frequency (F0)
      values were analyzed to determine whether the intonation of filled pauses is
      relative to, or independent of, prior prosodic context. Higher peaks were found
      to be systematically associated with higher filled-pause values, supporting the
      'relative' hypothesis. A linear model, in which filled-pause F0 was expressed as
      an invariant (over speakers) proportion of the distance between preceding peak F0
      and a speaker-dependent baseline F0, produced results nearly identical to those
      of a two-parameter model in which the coefficients of peak and baseline were
      allowed to vary freely. The model was less appropriate for filled pauses after
      sentence-initial peaks, but unaffected by temporal variables.

PMID- 8295926
TI  - Beyond sentence prosody: paragraph intonation in Dutch.
AB  - The present research aims at a partial model for synthesized text intonation,
      restricted to utterances consisting of a single intonation phrase. Intonational
      characteristics of short utterances in different positions within a paragraph are
      investigated. The effects of position in the paragraph on sentence prosody are
      mainly located in the beginning of the utterance. A model is formulated to
      capture the main findings. The model is then perceptually evaluated. The results
      indicate that the model can be used to improve the naturalness of rule-based
      intonation in a system for automatic text-to-speech conversion.

PMID- 8295927
TI  - The prosody of information units in spontaneous monologue.
AB  - This article describes a perceptual evaluation of the prosodic structure of a
      spontaneously produced monologue. It was found that the speaker studied
      demarcates larger-scale topical units in spoken discourse by means of intonation
      (use of melodic boundary markers, scaling of maxima in pitch movements, general
      decline in average pitch) and by the use of pauses with variable durations. In a
      perception test, it was examined to what extent these prosodic devices may be
      important to listeners. Subjects were confronted with three unintelligible (band
      pass-filtered) versions of a fragment of the elicited monologue: (1) with the
      original prosody unchanged; (2) with constant pause duration and the original
      speech melody; (3) with monotonous pitch and the original pause structure. They
      were instructed to indicate the boundaries of the larger-scale topical units in
      the three versions. Subjects were able to detect correctly the major discourse
      boundaries in all three filtered versions in a significant number of cases. They
      performed best when confronted with version 1. Versions 1 and 2, in their turn,
      did better than version 3, which suggests that, in the performance of this
      speaker, intonation is a perceptually more important factor than pause for the
      clarification of the topical make-up of a text, though the latter dimension is
      certainly not negligible.

PMID- 8295928
TI  - A gestural production model and its application to reduction in German.
AB  - A quantitative speech production model has been computer-implemented based on
      specifications of gestures as its input. Articulatory gestures serve the central
      role of phonological/phonetic units in speech organization. The present model is
      not based on task dynamics, but it still assumes a critically damped linear
      second-order system. The capability of this model is partially demonstrated by
      its application to reduction phenomena in conversational speech in German.
      Explanations in terms of timing and magnitude alterations of gestures in
      different articulators use only a few general principles for a variety of
      apparent segmental alterations. Some salient examples have been synthesized based
      on the current model, which also contributed to the evaluation of the parameter
      values involved in sample gestures.

PMID- 8295929
TI  - Phonetic and phonological features of approximants in Athabaskan and Eskimo.
AB  - The Athabaskan and Eskimo approximants, particularly [j], [w], and [symbol: see
      text], behave phonologically like obstruents. In both language families, [j],
      which alternates with a sibilant, is phonologically [+coronal], although its
      coronality has been questioned on phonetic grounds. These approximants best
      illustrate Sapir's [1925] notion of 'a true point in pattern' which must be
      defined 'over and above its natural [phonetic] classification on organic and
      acoustic grounds'. The fact that approximants are classified phonologically as
      sonorants or obstruents in different languages is incompatible with the
      universality of distinctive features and their phonetic properties. This problem
      is resolved by placing a phonological boundary for [+/-sonorant] somewhat
      differently in the continuum of the sonority hierarchy, depending on how
      approximants behave in individual languages.

PMID- 8295930
TI  - Cross-language influence on the production of Mandarin /f/ and /x/ and Taiwanese
      /h/ by native speakers of Taiwanese Amoy.
AB  - The present study examines the patterns of interference between a first (here,
      Amoy) and second language (here, Mandarin) by comparing the production of a
      Mandarin phone [f] (a 'new' phone) with another Mandarin phone [x] (which is
      'similar' to an Amoy phone [h]) by three groups of native Amoy subjects
      differentiated by proficiency in Mandarin. Their Mandarin production was also
      compared to that of Mandarin monolinguals. The spectrum of each consonant was
      analyzed to show the frequency range and energy of the fricative. In general,
      native Amoy speakers interpreted Mandarin /f/ and /x/ in terms of their first
      language phones [hw], but showed different patterns of interference for different
      proficiency levels. The least proficient simply substituted the Amoy phones for
      the Mandarin. More proficient speakers could approximate the Mandarin monolingual
      phonetic norm for the 'new' phone [f] more accurately than for the 'similar'
      phone [x]. The most proficient showed little Amoy-to-Mandarin interference on
      even the 'similar' phone [x]. On the other hand, the most proficient showed some
      interference from Mandarin /x/ on their Amoy production.

PMID- 8295931
TI  - Chaos and physiology: deterministic chaos in excitable cell assemblies.
AB  - In this review we examined the emerging science of deterministic chaos (nonlinear
      systems theory) and its application to selected physiological systems. Although
      many of the popular images of fractals represent fascination and beauty that by
      analogy corresponds to nature as we see it, the question remains as to its
      ultimate meaning for physiological processes. It was our intent to help clarify
      this somewhat popular, somewhat obscure area of nonlinear dynamics in the context
      of an ever-changing procedural base. We examined not only the basic concepts of
      chaos, but also its applications ranging from observations in single cells to the
      complexity of the EEG. We have not suggested that nonlinear dynamics will answer
      all of our questions; however, we did attempt to illustrate ways in which this
      approach may help us to answer new questions and to rearticulate old ones. Chaos
      is revolutionary in that the overall approach requires us to adopt a different
      frame of reference which, at times, may move us away from previous concerns and
      methods of data analysis. In sections I-IV, we summarized the nonlinear dynamics
      approach and described its application to physiology and neural systems. First,
      we presented a general overview of the application of nonlinear dynamical
      techniques to neural systems. We discussed the manner in which even apparently
      simple deterministic systems can behave in an unpredictable manner. Second, we
      described the principles of nonlinear dynamical systems including the derived
      analytical techniques. We now see a variety of procedures for delineating whether
      frenetic chaotic behavior results from a nonlinear dynamical system with a few
      degrees of freedom, or whether it is caused by an infinite number of variables,
      i.e., noise. Third, we approached the applications of nonlinear procedures to the
      cardiovascular systems and to the neurosciences. In terms of time series, we
      described initial studies which applied the now "traditional" measures of
      dimensionality (e.g., based on the algorithm by Grassberger and Procaccia) and
      information change (e.g., Lyapunov exponents). Examples include our own work and
      that of Pritchard et al., demonstrating that the dynamics of neural mass activity
      reflect psychopathological states. Today, however, the trend has expanded to
      include the use of surrogate data and statistical null hypotheses testing to
      examine whether a given time series can be considered different from that of
      white or colored noise (cf. Ref. 262). One of the most important potential
      applications is that of quantifying changes in nonlinear dynamics to predict
      future states of the system.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8295932
TI  - Cellular defenses against damage from reactive oxygen species.

PMID- 8295933
TI  - Transport of macromolecules across microvascular walls: the two-pore theory.
AB  - In this review we summarized the evidence favoring the concept that the major
      plasma proteins are passively transported across vascular walls through water
      filled pathways by means of convection and diffusion. With regard to solute
      transport, a majority of microvascular walls seems to show a bimodal size
      selectivity. This implies the presence of a high frequency of functional small
      pores, restricting proteins, and an extremely low number of non-size-selective
      pathways, permitting the passage of macromolecules from blood to tissue, here
      denoted large pores. We discussed the general behavior of such a heteroporous
      system. A major consequence of two-pore heteroporosity is that large-solute
      transport must mainly occur due to convection through large pores at low
      filtration rates, that is, at normal or even zero lymph flows. Indeed, convection
      must be the predominating transport mode for most solutes across large pores when
      the net filtration rate is zero. Under these (transient) conditions, the
      convective leak of macromolecules across large pores will be counterbalanced by
      absorption of essentially protein-free fluid through protein-restrictive pores.
      In a heteroporous membrane, proteins can thus be transported by solvent drag
      across vascular walls in the absence of a net convection. Normally the steady
      state transcapillary fluid flow (lymph flow) is about equally partitioned among
      small and large pores, which makes lymph essentially a "half and half" mixture of
      protein-free ultrafiltrate and plasma. With increasing fluid flows, however, the
      plasma filtrate will be progressively diluted, eventually reaching a protein
      concentration largely in proportion to the fractional hydraulic conductance
      accounted for by the large pores (alpha L). Under these high lymph flow
      conditions, not only the large-pore transport but also the small-pore transport
      (of smaller macromolecules) will become convective. At low lymph flows, however,
      the small-pore transport of smaller macromolecules is usually mostly diffusive.
      An important implication of capillary heteroporosity is that single-pore
      formalism is inadequate for correctly evaluating the capillary sieving
      characteristics. With the use of homoporous transport formalism, the "lumped"
      macromolecular PS and sigma will therefore vary as a function of transcapillary
      fluid flow (Jv). However, it is approximately correct to use single-pore
      formalism for conditions when Jv is very high during steady state. Thus, if
      minimal sieving coefficients can be measured for macromolecules, then these
      values will accurately reflect (1 - sigma).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8295934
TI  - Energy metabolism and contractility in ectothermic vertebrate hearts: hypoxia,
      acidosis, and low temperature.

PMID- 8295935
TI  - Cellular mechanisms of muscle fatigue.
AB  - Fatigue, defined as the failure to maintain the required or expected power
      output, is a complex problem, since multiple factors are clearly involved, with
      the relative importance of each dependent on the fiber type composition of the
      contracting muscles(s), and the intensity, type, and duration of the contractile
      activity. The primary sites of fatigue appear to be within the muscle cell itself
      and for the most part do not involve the central nervous system or the
      neuromuscular junction. The major hypotheses of fatigue center on disturbances in
      the surface membrane, E-C coupling, or metabolic events. The cell sites most
      frequently linked to the etiology of skeletal muscle fatigue are shown in Figure
      1. Skeletal muscles are composed of at least four distinct fiber types (3 fast
      twitch and 1 slow twitch), with the slow type I and fast type IIa fibers
      containing the highest mitochondrial content and fatigue resistance. Despite
      fiber type differences in the degree of fatigability, the contractile properties
      undergo characteristic changes with the development of fatigue that can be
      observed in whole muscles, single motor units, and single fibers. The Po
      declines, and the contraction and relaxation times are prolonged. Additionally,
      there is a decrease in the peak rate of tension development and decline and a
      reduced Vo. Changes in Vo are more resistant to fatigue than Po and are not
      observed until Po has declined by at least 10% of its initial prefatigued value.
      However, the reduced peak power by which fatigue is defined results from both a
      reduction in Vo and Po. In the absence of muscle fiber damage, the prolonged
      relaxation time associated with fatigue causes the force-frequency curve to shift
      to the left, such that peak tensions are obtained at lower frequencies of
      stimulation. In a mechanism not clearly understood, the central nervous system
      senses this condition and reduces the alpha-motor nerve activation frequency as
      fatigue develops. In some cases, selective LFF develops that displaces the force
      frequency curve to the right. Although not proven, it appears likely that this
      condition is associated with and likely caused by muscle injury, such that the SR
      releases less Ca2+ at low frequencies of activation. Alternatively, LFF could
      result from a reduced membrane excitability, such that the sarcolemma action
      potential frequency is considerably less than the stimulation frequency.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8295936
TI  - Sensory innervation of the viscera: peripheral basis of visceral pain.

PMID- 8295937
TI  - Sex steroid regulation of chin-marking behavior in male New Zealand rabbits.
AB  - Chin-marking behavior (chinning) was evaluated daily in nine intact adult male
      rabbits. All subjects (Ss) displayed chinning (mean of means +/- SE = 61 +/- 7
      marks/10 min) but the frequency of this behavior varied largely across them
      (range of mean chinning frequency = 19-84 marks/10 min). Chinning frequency
      showed abrupt variations at intervals of 2-3 days, but periodogram analysis did
      not reveal the existence of an endogenous rhythm in this behavior. Castration
      significantly decreased (mean of means +/- SE = 29 +/- 9 marks/10 min; p < 0.01).
      but did not suppress chinning. Testosterone propionate (TP; 1 mg/day for 16 days)
      restored chinning in castrated Ss to slightly below precastration levels (mean +/
      S.E. V 53 +/- 13 marks/10 min). The daily administration of 1 microgram
      estradiol benzoate (EB) plus 1 mg dihydrotestosterone propionate (DHTP)
      stimulated chinning within 2 days (mean increase = 147%; p < 0.005). DHTP (1
      mg/day) given alone stimulated chinning only after 11 days of treatment (mean
      increase = 475%; p < 0.01). At higher doses, both DHTP (10 mg/day) and EB (10 or
      50 micrograms/day) stimulated chinning by 450%, 80%, and 100%, respectively, over
      baseline values. Results indicate that chinning largely depends on testicular
      steroids. Androgen receptor occupation by T or DHT, which is enhanced by E,
      optimally activates chinning.

PMID- 8295939
TI  - Spontaneously hypertensive rats (SHR) as a putative animal model of childhood
      hyperkinesis: SHR behavior compared to four other rat strains.
AB  - Childhood hyperkinesis or attention-deficit hyperactivity disorder (ADHD) is a
      behavior disorder of which the main symptoms are attention problems and
      hyperactivity. The main objective of the present study was to investigate whether
      the spontaneously hypertensive rat (SHR) strain is a useful animal model of ADHD.
      Five different rat strains were tested: SHR, Wistar-Kyoto (WKY), Wistar, Sprague
      Dawley (SPRD), and PVG (hooded) rats. The protocol consisted of three different
      test procedures: 1) A 7.5-min free-exploration open-field test (home cage
      accessible), where the SHR was less active than Wistar and SPRD but more active
      than WKY; SHR showed longer latencies to leave the home cage than both Wistar and
      SPRD rats, spending less time in the field, ambulating and rearing less than
      Wistar and SPRD but more than WKY. Within session, the SHR tended to be more
      active at the end of the session than at the start, while the opposite tended to
      be the case in the other groups. 2) A 7.5-min forced exploration open-field test
      (home cage not accessible), where the results showed that the SHR is less active
      than both the Wistar and Sprague-Dawley strains, but more active than PVG and
      WKY. 3) A two-component multiple schedule of reinforcement with a fixed interval
      2 min signalled by houselight on and a 5-min extinction signalled by houselight
      off. Lever pressing by SHR was markedly different from that of the other four
      strains, which were quite Except early in the interval, SHR pressed the lever
      more than any of the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295938
TI  - The influences of androgen on sociosexual behavior: a comparison between the
      spontaneously hypertensive (SHR) and the Wistar-Kyoto rat (WKY).
AB  - Differences in androgen-dependent forms of behavior and plasma testosterone
      levels in the spontaneously hypertensive rat (SHR) and its normotensive
      counterpart the Wistar-Kyoto rat (WKY) are described here. Copulatory behavior
      (solitary test to avoid influence of experience) and certain androgen-dependent
      elements of sociosexual orientation were significantly attenuated in the SHR
      compared to the WKY male rat. After castration, the differences in sociosexual
      orientation were no longer apparent. In contrast, differences in other behavioral
      elements, such as locomotion, were unchanged after castration. Plasma
      testosterone levels were significantly higher in the SHR than in the WKY male
      rats. Taken together, the behavioral and hormonal data suggest a decreased
      central nervous responsiveness to androgens in the SHR rats. This could lead to
      reduced androgen-dependent behavior, and possibly also to a decreased
      testosterone feedback control.

PMID- 8295940
TI  - The influence of exercise on energy balance changes induced by ventromedial
      hypothalamic lesion in the rat.
AB  - The effects of a hypothalamic ventromedial area lesion on energy balance were
      tested in exercising rats and in sedentary rats to add further information about
      the type of obesity developed after ventromedial lesion. Four groups of six male
      Sprague-Dawley rats were used. Group 1: sham-lesioned and sedentary rats, which
      were utilized as control rats (C); group 2: sham-lesioned and exercising rats
      (E); group 3: lesioned and sedentary rats (L); group 4: lesioned and exercising
      rats (LE). The exercise consisted of daily swimming for 30 min. Resting oxygen
      consumption, food intake, and body weight were measured before any treatment and
      3 weeks after the lesion or/and the exercise period. The results showed that the
      oxygen consumption increased in the E and LE groups but not in the C and L
      groups. Food intake increased more in E and LE groups than in L group. The
      increases in body weight were higher in L and LE than in the E and C groups.
      These findings suggest that exercise modifies resting oxygen consumption and food
      intake in lesioned rats, but does not influence the degree of obesity. Thus, the
      ventromedial syndrome can be considered a type of obesity not completely
      unregulated.

PMID- 8295941
TI  - An unexpected role of the cerebellum: involvement in nutritional organization.
AB  - The influence of cerebellectomy in nutritional function was studied in the rat.
      Feeding behavior and analyses of lipids, proteins, nitrogen, and catecholamines
      in fecal and urinary excreta and in plasma were studied in 20 cerebellectomized,
      20 sham operated, and 20 control animals. The results demonstrate that feeding
      behavior (quantitative rates of daily absorbed food, body weight, and the choice
      of the nutriment form) was lower in cerebellectomized animals compared to sham
      operated and control animals. Rates of steatorrhea and urinary levels of
      vanylmandelic acid, homovanillic acid, and metanephrine were higher in
      cerebellectomized animals while plasma levels of proteins, fatty acids, and
      glycerol were lower. Thus, the cerebellum is involved in nutritional regulation
      in the rodent.

PMID- 8295942
TI  - Nonnutritive sucking by the calf and postprandial secretion of insulin, CCK, and
      gastrin.
AB  - Early weaned calves were allowed to suck on a dry rubber teat after drinking
      milk, and samples of blood from the hepatic portal vein and from the jugular vein
      were assayed for insulin, CCK, and gastrin to determine if nonnutritive sucking
      affected digestive hormone secretion. Postprandial changes in concentrations of
      all hormones showed a biphasic response with an initial rapid increase, later
      followed by a slower increase. In the portal vein, peak postprandial
      concentrations of insulin and concentrations of CCK 60 min after the meal were
      higher when the calves could suck the teat after the meal. There was a positive
      correlation between the time spent sucking the teat and the increase in insulin
      and CCK concentrations. Nonnutritive sucking did not significantly increase
      gastrin concentrations, nor were concentrations of insulin and CCK in the jugular
      vein affected. The performance of normal appetitive feeding behavior can directly
      affect digestive hormone secretion even if nutrient intake is not affected.
      Deprivation of normal sucking behavior cannot be assumed to be inconsequential
      for the well being of calves.

PMID- 8295943
TI  - Food deprivation- vs. intraventricular adrenaline-induced feeding and
      postprandial behaviors in the pigeon (Columba livia).
AB  - The present study was designed to investigate possible similarities between the
      feeding and postprandial behavioral profile observed after different periods of
      food deprivation and after intracerebroventricular (ICV) injections of adrenaline
      (A) (30 nmol/microliter) in satiated pigeons (Columba livia). The results
      indicate that the postprandial sleep-like behavior increases observed after A
      treatment are similar only to those observed after prolonged periods of fasting.
      These parallel behavioral effects are discussed as representing the product of
      similar levels of satiety signals, obtained after equivalent signaling of
      challenges to energy homeostasis, in both 96-h deprived and A-treated animals.
      Our data may also suggest that ICV A injections evoke a central state comparable
      to that of prolonged fasting, and that this neurotransmitter may participate as a
      chemical mediator in the regulation of food intake in the pigeon.

PMID- 8295944
TI  - Antinociceptive and hypothermic crosstolerance between continuous and
      intermittent cold-water swims in rats.
AB  - Antinociceptive responses induced by continuous (CCWS: 2 degrees C, 3 min) and
      intermittent (ICWS: 2 degrees C, 18 10-s swims, 18 10-s recoveries) cold-water
      swims differ in their sensitivity to opioid antagonists and crosstolerance with
      morphine. The present study examined whether CCWS and ICWS antinociception and
      hypothermia displayed crosstolerance in rats. Jump thresholds were significantly
      increased following acute exposure to CCWS (30 min) and ICWS (30-60 min). CCWS
      antinociception displayed tolerance (90% reduction) to CCWS after 14 days and
      crosstolerance (100% reduction) to ICWS on the fifteenth day. ICWS
      antinociception displayed tolerance (74% reduction) to ICWS and crosstolerance
      (81% reduction) to CCWS. Core body temperatures were significantly decreased
      following acute exposure to CCWS (30 min) and ICWS (30-90 min). Although CCWS and
      ICWS hypothermia displayed tolerance to the same stressor and crosstolerance to
      the other stressor, the changes in the antinociceptive and hypothermic effects
      failed to correlated significantly with each other.

PMID- 8295945
TI  - Relative androgen sensitivity of the vascular and striated-muscle systems
      regulating penile erection in rats.
AB  - In this study we sought to compare the androgen sensitivity of the penile
      vascular erectile system with that of the striated muscles that augment the
      vascular effectors. All males were castrated 2 weeks before the experiments. At
      the time of castration, all males were implanted SC with a 45-mm testosterone (T)
      filled Silastic capsule to maintain reflexive erections in ex copula tests.
      Experimental males had the bulbospongiosus (bulbocavernosus and levator ani) and
      ischiocavernosus muscles removed, while control animals underwent sham muscle
      excision surgery. After two baseline penile reflex tests, the T capsules were
      removed, and the groups were compared for the rate of loss of penile responses
      over 5 weeks. After these tests were completed, the T capsules were reimplanted
      and the two groups were compared for the rate of restoration of penile reflexes.
      These tests were conducted at 6, 12, 24, 36, 48, 72, and 96 h after
      reimplantation of the T capsules. Our results demonstrated that the vascular
      effector mechanisms responsible for initiating erections are androgen sensitive.
      The effects of T withdrawal and replacement on erection latency and low intensity
      erections (E1s) were manifested at about the same rate in the vascular and
      striated muscle effector systems. In contrast, the restoration of moderate
      intensity erections (E2s) by T occurred at a faster rate in rats with intact
      penile muscles. This result suggests that T was acting on the striated muscle
      effector systems to augment penile erection during this time, presumably due to
      the bulbospongiosus muscle exerting greater force on the penile bulb.

PMID- 8295946
TI  - Food search demand effort effects on behavior and cortisol in adult female
      squirrel monkeys.
AB  - Laboratory-born, group-housed, ovariectomized adult female squirrel monkeys
      (Saimiri sciureus) were exposed to feeding conditions in which the availability
      and accessibility of food were altered. Both high- and variable-demand feeding
      conditions were utilized. The variable-demand condition required alternating
      periods of high effort (120% of normal daily intake presented) and low effort
      (600% of normal daily intake presented) to obtain food for 10-12 weeks. An
      additional group was exposed solely to the high-demand condition for 10 weeks.
      Blood samples were obtained weekly, and behavioral observations were conducted
      daily. In the variable-demand condition, plasma cortisol was elevated above
      baseline during the periods of high effort. For the constant high-demand group,
      cortisol was elevated for the duration of the experimental treatment. Contact
      with other animals, as well as a species-specific inactive posture, decreased as
      a result of exposure to high demand. Maintenance of body weight indicated that
      nutritional deprivation did not occur. The imposition of increased food-seeking
      efforts provides an ecologically relevant and noninvasive method of producing
      chronic stress in the squirrel monkey.

PMID- 8295947
TI  - Discrimination of insulin-produced hypoglycemia in rats.
AB  - Hypoglycemia is an abnormal state that can be induced by administering insulin to
      a fasting animal. Rats were trained to discriminate the normal state of
      euglycemia from the hypoglycemia produced by injection of 6 units/kg insulin. A
      drug discrimination procedure was used with a two-lever operant response. Insulin
      or water injected 25 min prior to the operant sessions determined whether left or
      right lever presses were reinforced. During 40 training sessions, reliable
      discrimination of the insulin-produced cue developed. After insulin injection,
      mean blood glucose levels dropped to about 75% of preinjection values. At 12 min
      postinsulin injection, prior to the development of hypoglycemia, noninsulin
      responses were made. Noninsulin responses were also made after injection with 800
      mg/kg ethanol, indicating that a novel interoceptive state did not substitute for
      the insulin-produced cue. Insulin injections produced less severe hypoglycemia in
      less food-deprived rats, which again gave noninsulin responses. Animals can be
      trained to recognize the insulin-produced state, which presumably involves
      hypoglycemia, and/or counterregulatory process evoked in response to the drop in
      blood glucose.

PMID- 8295948
TI  - Schedule-induced polydipsia in rats with gastric fistulas.
AB  - We have investigated the development and maintenance of schedule-induced
      polydipsia (SIP) when ingested water (and food) was allowed to drain from the
      stomach. Fourteen male Long-Evans rats were prepared with permanent gastric
      cannulas and, after recovery, their body weight was reduced to 80%. Water intake
      was measured, with cannulas open or closed, during 42 daily 1-h sessions in which
      45-mg food pellets were delivered one per minute. Allowing ingested material to
      drain from the stomach impaired the development of SIP and reduced the polydipsia
      in rats in which SIP had already been established. In contrast, opening the
      gastric fistulas increased drinking in these rats when all the food pellets were
      provided at once or after water deprivation. The opposite effects of gastric
      drainage on dehydration and schedule-induced drinking is consistent with the view
      that SIP is not a fluid-regulating phenomenon. It is not clear, however, how
      these unexpected findings fit current hypotheses to explain SIP that are based on
      oral, neural excitatory, or emotional mechanisms.

PMID- 8295949
TI  - Dissociation between behavioral and corticosterone responses on repeated
      exposures to cat odor.
AB  - Rats exposed for 5 min to a phobic stimulus (the odor of a cat) had plasma
      corticosterone concentrations significantly higher than those exposed to a
      neutral odor and than a group remaining undisturbed in the animal house. During
      the first exposure to cat odor the increased corticosterone was related to the
      avoidance behavior, measured as the time spent sheltering. After five exposures
      to cat odor the rats continued to avoid the odor cloth, but no longer responded
      with raised corticosterone levels. The results are discussed with reference to
      the two components of a phobic response (avoidance and disturbance), and it is
      suggested that the latter, reflected by changes in corticosterone, habituates
      more readily than the former.

PMID- 8295950
TI  - Age differences in the controls of ring doves' pecking.
AB  - Three experiments investigated the endogenous and exogenous controls of ring dove
      pecking. Experiment 1 confirmed that deprivation modulates adult pecking although
      nondeprived subjects peak at high levels. Experiment 2 determined that the level
      of pecking in nondeprived birds is modulated by exogenous cues such as the
      salience of the seed. Experiment 3 analyzed some of the controls of pecking in
      squabs. Both nondeprived and deprived squabs pecked little on days 12 and 16 of
      life, but by day 18, deprived squabs pecked significantly more than nondeprived
      squabs. Squabs inexperienced with deprivation peck less when hungry than squab
      that have had previous experience with deprivation. The controls of feeding
      change between day 24 of life and adulthood as exogenous cues did not stimulate
      nondeprived squab pecking until day 24 of life.

PMID- 8295951
TI  - Sex differences in anxiety behavior in rats: role of gonadal hormones.
AB  - These experiments examined the role of gonadal hormones at both the
      organizational and activational time periods on sex differences in plus-maze
      behavior. In the first experiment, adult female Long-Evans rats were found to
      spend more time on the open arms of the plus maze than adult males, indicating
      less anxious behavior. In the second experiment, male and female subjects
      received a neonatal treatment (chemical castration with flutamide or tamoxifen,
      vehicle injection, or no injection) and a prepubertal treatment (gonadectomy,
      sham surgery, or no surgery). Adult females receiving either neonatal tamoxifen
      or prepubertal ovariectomy spent less time on the open arms than control females,
      but females who received both treatments were the most defeminized subjects.
      Males were not affected by the absence of gonadal hormones at either time period.
      These experiment indicate that female gonadal hormones play an important role
      both organizationally and activationally in plus-maze behavior. The role of the
      GABA receptor complex in mediating this effect is discussed. Knowledge of sex
      differences in plus-maze behavior may help to make this maze a more useful tool
      in investigating anxiety behavior in rats.

PMID- 8295952
TI  - Individual behavioral differences and ethanol consumption in Wistar rats.
AB  - The aim of this study was to determine if inherent differences in the behavioral
      measures between individual Wistar male rats influence the level of ethanol
      consumption. We addressed this question by searching for differences in ethanol
      intake that an individual animal develops. Measures of ethanol intake were then
      correlated with the outcome of various behavioral tests. Our results indicate
      that individual variations of behavioral reactivity may be associated with the
      predisposition to develop high ethanol intake. Animals with delayed habituation
      to a novel environment, enhanced locomotor activity during testing in the open
      field after initial habituation, and excessive locomotor inhibition after
      administration of 0.07 mg/kg dose of apomorphine, are predisposed to develop high
      ethanol intake in a free-choice condition. Measures of activity in the forced
      swim test, apomorphine-induced stereotypy, hypothermia, and locomotor stimulation
      could not predict a propensity to acquire high ethanol preference. It is
      suggested that individual differences in the acquisition of high ethanol intake
      may be influenced, at least partially, by the differences in the sensitivity of
      brain dopaminergic neurotransmission.

PMID- 8295953
TI  - Effects of bilateral lesions of auditory cortex in mice on the acoustic startle
      response.
AB  - The acoustic startle response (ASR) was used to investigate the effects of
      auditory cortical lesions on a brain stem-mediated auditory behavior. The ASRs
      were obtained longitudinally from young adult C57BL/6J mice before bilateral
      ablation of auditory cortex, 1 day after ablation, and 1 month later. Control
      mice received lesions of nonauditory cortex. For some mice, averaged brain stem
      evoked responses (ABR) were obtained, and these indicated no effects of lesions
      on auditory sensitivity. One month after surgery, mice with auditory cortex
      ablations were statistically indistinguishable from controls on all
      suprathreshold measures of ASR. However, 1 day after ablation of auditory cortex,
      experimental animals (but not controls) exhibited a change in ASR amplitude (but
      not threshold or latency). When a noise burst of 80 dB SPL was used to elicit the
      ASR, the amplitude was diminished, but with a 110 dB stimulus, amplitude was
      enhanced. The findings can be interpreted in one of two ways: temporary
      interference with modulation of the ASR normally performed by auditory cortex; or
      a general effect of auditory cortex ablation on brain stem auditory circuits not
      specific to the ASR. In any event, if auditory cortex plays a modulatory role
      with regard to the ASR, it is apparently nonessential and/or readily compensated
      for after ablation.

PMID- 8295954
TI  - Counterregulatory hormone responses during graded hyperinsulinemic euglycemia in
      conscious rats.
AB  - It has been suggested that hyperinsulinemia per se may affect the levels of some
      counterregulatory hormones in the absence of hypoglycemia. We studied the effect
      of graded hyperinsulinemia and concomitant increased glucose metabolism on the
      levels of counterregulatory hormones by means of the 5-step sequential
      hyperinsulinemic euglycemic clamp technique, combined with [3-3H]-glucose
      infusion, in conscious rats. Insulin infusion rates (IIR) of 0, 0.5, 1, 3, and 16
      mU/min, resulted in steady-state plasma insulin levels (mean +/- SEM) of 24 +/-
      4, 44 +/- 3, 98 +/- 8, 418 +/- 48, and 6626 +/- 361 microU/ml, peripheral glucose
      uptake (PGU) of 3.1 +/- 0.2, 3.6 +/- 0.3, 5.4 +/- 0.3, 9.2 +/- 0.4, and 12.4 +/-
      0.2 mg/min and hepatic glucose production (HGP) of 3.1 +/- 0.2, 2.4 +/- 0.4, 0.8
      +/- 0.3, -0.1 +/- 0.2, and -0.5 +/- 0.3 mg/min, respectively. Plasma glucagon
      levels were half maximally suppressed between IIRs of 0.5 and 1 mU/min and
      maximally suppressed at 3 mU/min. The suppression exactly paralleled the
      inhibition of HGP (r = 0.87 +/- 0.04, p < 0.02) but not the stimulation of PGU (r
      = -0.66 +/- 0.12, p = NS). This suggests that the inhibition of HGP by insulin is
      at least partially mediated by a simultaneous suppression of plasma glucagon
      levels. The adrenal hormones corticosterone and epinephrine were not influenced
      during the clamp.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295955
TI  - Modulation of the in vivo antibody response by a benzodiazepine inverse agonist
      (DMCM) administered centrally or peripherally.
AB  - Exposure to stressors can result in changes in immune function. Although there is
      increasing information concerning the peripheral hormonal and neural mediators of
      stress-induced changes in immune function, there is little information concerning
      the central nervous system mechanisms that lead to the peripheral changes. The
      following experiments examined the possible involvement of the benzodiazepine
      GABAA-chloride complex in modulation of the in vivo antibody response. Rats were
      given either peripheral or intracerebroventricular injections of methyl-6,7
      dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), a drug that has been shown
      to act at the benzodiazepine-GABAA complex and produces a behavioral state
      similar to anxiety. Rats were then immunized with keyhole limpet hemocyanin (KLH)
      and serum levels of KLH-specific antibody were measured for 2 weeks after
      immunization. Both peripheral and central administration of DMCM modulated the in
      vivo antibody response. The dose-response relationship of DMCM and changes in
      antibody levels was nonmonotonic, with high doses resulting in an increase in
      serum antibody levels and moderate doses resulting in a decrease in serum
      antibody levels. A possible role of the benzodiazepine-GABAA system in stress
      induced immunomodulation is discussed.

PMID- 8295956
TI  - Affinity of hepatic glucocorticoid receptors is influenced by energy/feeding
      status.
AB  - Genetically obese animals have been shown to have a reduced number and affinity
      of glucocorticoid receptors. The relationship between the alterations in receptor
      binding and the regulation of energy balance is not known. We sought to determine
      the role of body energy/feeding status on the binding characteristics of
      glucocorticoid receptors. To accomplish this, we examined the effect of long-term
      food restriction on the number and affinity of hepatic glucocorticoid receptors
      from Sprague-Dawley rats. After 3 weeks of food restriction (40% of ad lib),
      animals were bilaterally adrenalectomized. Livers were removed, a crude cytosolic
      glucocorticoid receptor fraction was isolated, and radioreceptor assays were
      performed. Glucocorticoid receptors from food-restricted rats showed a
      significant reduction in the dissociation constant (Kd) as compared to receptors
      derived from free-feeding controls. No difference in receptor number was
      observed. These results suggest that energy or feeding status of the animal may
      influence the affinity of hepatic glucocorticoid receptors, while receptor number
      may be independent of this status.

PMID- 8295957
TI  - Temporal segregation in coexisting Acomys species: the role of odour.
AB  - To understand the mechanisms underlying displacement (the shift from nocturnal to
      diurnal activity), in one of the two coexisting spiny mice (genus Acomys), the
      effect of chemical cues released by A. cahirinus on the time of activity of A.
      russatus was tested Six golden spiny mice (A. russatus), which prior to the
      experiments were kept separate from common spiny mice (A. cahirinus), showed
      nocturnal activity. They were exposed to chemical cues from the urine and faeces
      of conspecific and heterospecific mice of the opposite sex. The onset of activity
      in these mice was recorded. While the urine and faeces of conspecific mice did
      not have a significant effect on the time of onset of activity, heterospecific
      urine and faeces did cause a significant (p < 0.001) time shift and, a day after
      they were introduced, activity started 6.8 +/- 1.9 h earlier. This shift also
      took place on the second day. The results of this study suggest that the
      mechanism for displacement of A. russatus from nocturnal activity is by chemical
      signals released by A. cahirinus. Therefore, it may be concluded that chemical
      cues maintain time separation between these two species.

PMID- 8295958
TI  - Anticonflict action of chlordiazepoxide in rats with combined lesions.
AB  - Lesions of brain areas thought to promote anxiety do not diminish the
      anticonflict effects of benzodiazepines (BZDs). After initial training in the
      lick-suppression conflict test, eight rats received electrolytic lesions of the
      amygdala, dorsal raphe, locus coeruleus, and mammillary bodies. Ten others
      received sham lesions. Postoperative testing revealed a significant increase in
      punished licking at two stages after surgery in lesioned animals when compared
      with their own preoperative baseline levels and with the punished licking of
      control animals. Systemic administration of chlordiazepoxide (CDP, 2.5-10.0
      mg/kg) resulted in a comparable dose-dependent increase in punished licking in
      both groups. These results suggest that the several structures lesioned need not
      be intact for CDP to have an antianxiety effect. It appears that sites of
      anxiolytic action are much more widely spread than currently believed and that
      other brain areas should be considered.

PMID- 8295959
TI  - Male-induced implantation failure (the Bruce effect) in mice: protective effect
      of familiar males on implantation.
AB  - Housing newly inseminated female mice in contact with a familiar male (a male
      that had cohabited with the female for 24 h during the pericopulatory period, but
      not the coital partner) depressed the implantation failure (the Bruce effect)
      induced by exposure to alien males. This is comparable to the protective effect
      of stud males on implantation in alien male-exposed females. The findings imply
      that exposure to a male (stud or any other) during the pericopulatory period
      enables the female to memorize the male-originating olfactory cues, and that this
      memory formation is not contingent upon mating. Reexposure to the male
      originating olfactory cues induces a luteotrophic effect in the newly inseminated
      female, which accounts for the protective effect of the stud/familiar male on
      implantation in the alien male-exposed female. The male-originating olfactory
      cues that provide the protective effect on implantation act through contact. The
      findings also lend support to the view that the female mouse is capable of
      identifying a male as an individual through olfactory cues perceived during the
      pericopulatory period.

PMID- 8295960
TI  - Orientation of pigeons exposed to constant light and released from familiar
      sites.
AB  - It has been proposed that homing pigeons may use pilotage to orient home when
      released from familiar sites. To test this possibility, a group of pigeons was
      released from familiar locations after being exposed to a constant bright light.
      This treatment produced the loss of the circadian rhythmicity of general activity
      of the birds and thus presumably impaired their time-compensating sun compass
      mechanism. Experimental birds, both anosmic and olfactorily unimpaired, did not
      show any tendency to orient home, their bearing distributions being generally not
      different from random. Their homing performances were also affected. These
      results show that initial orientation of pigeons released from familiar sites
      entails the use of the sun compass even when the birds are released after a
      treatment that makes them arrhythmic in their activity. The possibility that
      pilotage may play a role in the first part of the homing flight of pigeons
      remains to be demonstrated.

PMID- 8295961
TI  - Sex differences and stress response of WKY rats.
AB  - Wistar Kyoto (WKY), Fischer-344 (F-344), and Wistar male and female rats during
      either proestrus-estrus or diestrus phases of the estrus cycle were exposed to
      the ulcerogenic procedure of water restraint. Both male and female WKY rats
      revealed significantly more stomach ulcers as compared to Wistar and F-344 rats
      of the same sex. No persistent sex difference was observed, but ulcer severity
      was more pronounced during the proestrus-estrus phase as compared to the diestrus
      phase of the estrus cycle particularly in WKY female rats. In the second study,
      WKY females were observed as more active in the open-field test (OFT), but more
      immobile in the forced swim test (FST), as compared to WKY male rats. In
      addition, proestrus-estrus WKY females were less active in the OFT and
      significantly more immobile in the FST as compared to diestrus females. Thus,
      proestrus-estrus WKY females were judged as more emotional in the OFT and as
      exhibiting more signs of behavioral depression according to the FST. These
      studies suggest that the steroid hormone milieu in WKY rats may be responsible
      for these behavioral changes as well as the stress responsiveness in this stress
      susceptible rat strain.

PMID- 8295962
TI  - Level of corticosterone replacement determines body weight gain in
      adrenalectomized rats with VMH lesions.
AB  - Adrenalectomized female rats with lesions of the ventromedial hypothalamus or
      sham lesions were given SC implants of wax pellets or a fused mixture of
      corticosterone-cholesterol (40, 75, or 130% by weight). In animals with sham
      lesions, high dosages of corticosterone proved to be catabolic (r = -0.61 between
      plasma corticosterone and weight change). In marked contrast, animals with VMH
      lesions displayed substantial weight gains at all circulating levels of
      corticosterone, with a significant positive correlation (r = +0.48) between these
      two variables. It is concluded that: a) damage to the basomedial hypothalamus
      alters an organism's response to corticosterone at both ends of the dose-response
      curve, and b) both Type I and Type II corticosterone receptors in the brain play
      a role in hypothalamic obesity.

PMID- 8295963
TI  - Feeding behavior of grazing ruminants experiencing stress.
AB  - The mechanisms underlying diet selection of ruminants are less studied than those
      for monogastrics. However, recent studies have shown that these mechanisms may be
      more similar in ruminants and monogastrics than previously believed. Food
      aversion learning is observed in both monogastrics and ruminants, and the
      hypothalamic-pituitary-adrenal axis appears to be involved in avoidance learning.
      Using leafy spurge (Euphorbia esula), an introduced weed whose expansion has
      costly ecological and economic implications in western North America, as a model
      for underconsumed plant species, we hypothesized that sheep experience increased
      cortisol levels when they first consume leafy spurge and that this may be related
      to their reluctance to graze it. We also hypothesized that preexposure to leafy
      spurge would attenuate the development of a spurge-based aversion.
      Correspondingly, we hypothesized that preexposed sheep would not experience
      increased blood cortisol levels with leafy spurge gavage during an aversion
      trial. None of our hypotheses were disproved by the experiments. Our results lend
      support to the hypothesis that stress is required for the development of
      conditioned taste aversions and extend it to ruminants. We suggest that activity
      of the hypothalamic-pituitary-adrenal axis is integral to food aversion learning
      in ruminants.

PMID- 8295964
TI  - Relative preference for starch and sugar in rats.
AB  - When given a choice between fluids containing equal amounts of corn starch or
      glucose, Fischer rats preferred the fluid containing starch when the fluids
      contained 0.5%, 1%, 5%, or 20% carbohydrate, but not when the fluids contained
      10% carbohydrate. Fischer rats preferred 0.5% sucrose over 0.5% starch on the
      first day of testing, but then switched to preferring starch. Rats of the CD
      strain also preferred 0.5% starch over 0.5% sucrose or 0.5% glucose, but showed
      no reliable preference when offered a choice of 5% starch vs. 5% sucrose or 5%
      glucose. Most experiments used corn starch, but rats prefer 1% rice, wheat, and
      tapioca starch over 1% glucose. Rats given only one substance to drink, drank
      more fluid if the fluid contained 1% starch than if it contained 1% glucose.
      Preexposing rats to either glucose or starch for 3 days did not influence
      subsequent preference for starch over glucose. Since the starch and glucose
      mixtures used in the present work had the same number of calories, preference for
      starch over glucose must be attributed to the hedonic effects of starch flavor
      rather than to the postingestive effects of starch.

PMID- 8295965
TI  - Female meadow voles have a preferred mating pattern predicted by photoperiod,
      which influences fertility.
AB  - In a previous study, Meek and Lee found that female meadow voles mated within
      three distinct time periods after pairing with a male, and fertility was
      influenced by the time of mating and photoperiod. In the present studies, we
      tested the hypothesis that different patterns of mating would correlate with high
      and low fertility. We found two very different patterns of mating were correlated
      with high fertility. Females housed in long daylengths (long day; 14 h light/day)
      and mating within 48 h of pairing with a male, received few mounts,
      intromissions, and intromissions per ejaculatory series, with very short
      interintromission intervals. All long-day females utilizing this mating pattern
      ovulated, and 86-100% produced litters. We suggest this pattern of mating is
      associated with spontaneous estrus. In contrast to long-day females mating within
      48 h, females housed in short daylengths (short day; 10 h light/day) and mating
      between 14-48 h after pairing with a male, received significantly more short
      mounts and intromissions, with longer interintromission intervals. These short
      day females all ovulated and 86% produced litters. We suggest that this pattern
      of mating is associated with an induced estrus. Short-day females that did not
      exhibit this pattern of mating (66%) produced far fewer litters. We discuss two
      mechanisms by which fertility may be inhibited in most short-day females.

PMID- 8295966
TI  - Failure to induce rapid eye movement sleep by dark pulses in pigmented inbred rat
      strains.
AB  - Studies of albino Lewis rats, pigmented Brown Norway rats, and their F2 backcross
      progeny have demonstrated that the ability to trigger rapid eye movement (REM)
      sleep by turning off cage lights (dark pulses) is associated with albinism in
      these rat strains. Other studies have shown that pigmented inbred rats show REM
      sleep induction in the dark portion of short light:dark cycles or skin
      temperature changes. In the present study, these same pigmented breeds, Dark
      Agouti and hooded Long-Evans rats, were subjected to 5-min dark pulses and failed
      to show any evidence of REM sleep triggering. In fact, they showed trends towards
      REM sleep suppression during dark pulses. These results extend the finding that
      dark pulse triggering of REM sleep, readily evoked in albino rats, does not
      appear in pigmented rat strains.

PMID- 8295967
TI  - Chronic mild stress-induced anhedonia: greater effect in a genetic rat model of
      depression.
AB  - The effects of acute and chronic stressors on saccharin intake and preference in
      the hypercholinergic Flinders Sensitive Line (FSL) rat, a putative genetic animal
      model of depression, were studied and compared to the control Flinders Resistant
      Line (FRL) rats. Overall, the FRL rats drank significantly less saccharin and
      water than the FSL rats when compared over a wide range of saccharin
      concentrations (0.01-5%) under baseline conditions. A 0.02% saccharin
      concentration was used in subsequent experiments. We observed a significant
      suppression of saccharin intake/preference at 1 h following a single 5-min
      exposure to cold swim stress only in FSL rats. There was a tendency to increase
      saccharin intake in both lines at 1 h following a scrambled foot shock stress.
      These effects of acute stressors disappeared upon retesting for saccharin
      consumption/preference 23 h after the stress. Chronic 4-week exposure to
      unpredictable mild stressors significantly (p < 0.01) decreased saccharin
      consumption in the FSL rats, but not in the FRL rats. The FSL rats also exhibited
      a significantly greater decrease in saccharin preference (-24% vs. prestress
      baseline, as compared to -7% in FRL controls, p < 0.05). In conclusion, FSL rats
      appear more prone than the FRL rats to chronic, as well as immediate acute,
      stress-induced anhedonic effects. This outcome further supports the notion that
      the FSL rat is a useful model of a genetic predisposition to depressive-like
      reactions.

PMID- 8295968
TI  - The acquired control of ingestive behavior in the rat by flavor-associated
      postingestional stimulation.
AB  - Recently reported sham feeding studies have revealed that the rate of ingestion
      of liquid diets early in the ingestion interval is under the associative control
      of postingestive events occurring in the stomach and intestine. This study
      investigated the possibility that gastrointestinal filling induced by adding the
      nonabsorbable sugar alcohol mannitol to a test solution could serve as an
      unconditioned stimulus to support the acquired control of the initial rate of
      ingestion of a liquid by rats. The results revealed that mannitol had a direct
      unconditioned effect on the rate of decline in the rate of ingestion during the
      meal and that the association of it with a distinctive flavor resulted in an
      acquired control of the initial rate of licking conditioned to the flavor. The
      conditioned effect was rapidly acquired and rapidly extinguished. Our results
      demonstrate the preabsorptive mechano- or chemostimulation of the
      gastrointestinal tract can serve as a UCS to support the conditioning of the rate
      of ingestion early in the meal.

PMID- 8295969
TI  - Failure of a tryptophan-free amino acid mixture to modify sexual behavior in the
      female rat.
AB  - Female Wistar rats, weekly injected with estradiol valerate after ovariectomy,
      were trained to cause a sexual contact with a potent male by operating a lever.
      Contact-response latencies, which vary according to the nature of the sexual
      contact, were measured as an index of the female's sexual motivation. In these
      experimental conditions the administration of a tryptophan-free amino acid
      mixture, which has been proved to decrease brain serotonin and to enhance male
      mounting behavior, failed to modify the sexual motivation of the female rats.

PMID- 8295970
TI  - Culture in psychiatric diagnosis: an issue of scientific accuracy.
AB  - The revised version of the third edition of the American Psychiatric
      Association's (1987) Diagnostic and Statistical Manual of Mental Disorders (DSM
      III-R) gives scant attention to the significance of culture. Two paragraphs in
      the Introduction advising caution when using the Manual in different cultures
      (pp. xxvi-xxvii) are followed by more than 500 pages in which the relevance of
      culture remains basically unrecognized. This neglect is problematical:
      Ethnological research has repeatedly demonstrated the cultural plasticity of
      human behavior, so much so, in fact, as to controvert the unqualified attribution
      of psychiatric meaning to symptoms or sets of symptoms (Rogler, 1993). Yet,
      despite the scant attention given to culture, the DSM-III and its revised version
      are more widely used cross-nationally in teaching, research, and clinical
      practice than any other system for classifying mental illnesses (Maser et al.
      1991).

PMID- 8295971
TI  - Family therapy in a transitional society.
AB  - This paper is concerned with the application and adaptation of traditional models
      of family therapy as developed in Western societies, to the understanding and
      therapy of families in a society where the sociopolitical structures are changing
      rapidly. References were found in the literature only in connection with certain
      ethnic groups (Gray and Cosgrove 1985; McGoldrick-Pearce 1982), religious
      fellowships (Aradi 1988), and sociopolitical contexts (Auerswald 1983; Elkaim
      1982). The authors began to deal with these phenomena several years ago. Our
      first publication examined differences in religious, social, and class relations
      within the family and the way in which these factors affect family roles and
      their implementation (Furedi et al. 1989). Subsequent events directed our
      interest to the effects of political changes on family relationships and what the
      strategy of the family therapist could be in this situation.

PMID- 8295972
TI  - Psychotherapy and supervision with a bereaved Moslem family: an intervention that
      almost failed.
AB  - Families responding to loss are units that function and are embedded in
      particular cultural frameworks. The adequate clinician learns to work with
      different individuals and problems over time, and in this process he or she
      learns about the importance of a range of variables including sex roles, age,
      socioeconomic circumstance, and the like. In parallel fashion, the developing
      clinician also learns to work with different cultural and religious contexts as
      they affect and frame the client's experiences.

PMID- 8295973
TI  - Holocaust cancer patients: a comparative study.
AB  - There is as yet no consensus on the long-term effects of severe life-threatening
      stresses. In an earlier study (Baider et al. 1992), we gained some understanding
      of this issue by addressing a specific question: How do individuals who have
      undergone severe stress in the past cope with a current stress? We investigated
      whether severe stress occurring in the past had a long-term effect on present
      coping capabilities. We addressed the question by studying a group of Holocaust
      survivors (severe past stress) who were diagnosed as having cancer (current
      stress) and compared them to a matched group of cancer patients with no past
      history of trauma. The matching was done on most demographic variables (gender,
      age, marital status, and education), as well as on disease variables (site and
      stage of cancer, time since cancer diagnosis, previous and present treatments).
      The results were unequivocal.

PMID- 8295974
TI  - Pathological grief: an intensive case study.
AB  - Pathological mourning is such an excessive, blocked, or distorted process that
      psychiatric signs and symptoms develop. Explanation of how and why these signs
      and symptoms form could deepen an understanding of both normal and pathological
      mourning. Because many variables are involved in such explanations, intensive
      case study is a desirable methodology because it permits a detailed look at how
      various factors interact (Brewer and Hunter 1989; Luborsky and Mintz 1972;
      Luborsky and Spence 1971; Nessleroade and Ford 1985). While a patient may
      complain of symptoms as experiences that endure or occur episodically over days
      and weeks, a clinician observes psychiatric signs in the here-and-now seconds and
      minutes of an interview. Relating signs and symptoms to each other and to other
      variables in order to form a theoretical model of their formation requires
      exploration of data across long and short time frames. It is important to
      understand how the here-and-now phenomena combine to form patterns across longer
      periods of the individual's life. Hence, we developed a combined macro- and
      microanalytic approach to intensive case studies.

PMID- 8295975
TI  - Psyclops: an exploratory graphical system for clinical research and education.
AB  - We present Psyclops, an interactive computer graphic system designed to help
      address a growing information dilemma in the examination of individual
      psychiatric cases. Ever more information is needed to better understand conscious
      experience, interpersonal behavior, and the formation of psychiatric signs and
      symptoms, yet the information load already exceeds our usual methods of handling
      it. Psyclops consists of a suite of software modules, manual sections, and
      standards that have been developed according to guiding concepts intended to help
      one collect, organize, access, and explore complex data about a single subject
      for research, education, and ultimately, clinical care purposes. This document
      provides background in clinical information science and a description of the
      system; the reader interested in its application in clinical research theory
      development is referred to the companion paper in this issue (Horowitz et al.,
      Pathological Grief: An Intensive Case Study).

PMID- 8295976
TI  - Varieties of near-death experience.
AB  - Near-death experiences are profound subjective events frequently reported by
      individuals who have come close to death. They are of importance to mental health
      professionals, not only because they often happen to patients under our care, but
      because they have been reported to produce widespread and long-lasting changes in
      values, beliefs, and behavior that dramatically affect the experiencers'
      attitudes toward living and dying (Bates and Stanley 1985; Bauer 1985; Flynn
      1982; Greyson 1983b; Noyes 1980; Ring 1984). Several studies, including surveys
      of recently resuscitated hospitalized patients (Ring 1980; Sabom 1982) and a
      nationwide poll of the general population (Gallup and Proctor 1982) have
      estimated that near-death experiences are reported by 30%-40% of individuals who
      come close to death, or about 5% of the adult American population.

PMID- 8295977
TI  - Activity and protein distribution of 12-lipoxygenase in HEL cells: induction of
      membrane-association by phorbol ester TPA, modulation of activity by glutathione
      and 13-HPODE, and Ca(2+)-dependent translocation to membranes.
AB  - The understanding of the intracellular regulation of 12-lipoxygenase requires a
      knowledge of the distribution of both enzyme protein and its activity. In human
      erythroleukemia cells, the membrane fraction contains about 90% of the total
      cellular 12-lipoxygenase activity, whereas only approximately 10% of 12
      lipoxygenase activity resides in the cytosol. However, the majority of the
      cellular 12-lipoxygenase protein is found in the cytosol. Pretreatment of cells
      for 0-3 days with 160 nM TPA caused a marked, time-dependent increase in membrane
      bound 12-lipoxygenase activity and protein, respectively. In contrast, the
      cytosolic amount of 12-lipoxygenase protein and activity, respectively, were
      minimally altered by this TPA treatment. Recombining the active membrane fraction
      with cytosol resulted in no significant inhibition of its 12-lipoxygenase
      activity, but the addition of GSH to the membrane fraction inhibited 12
      lipoxygenase activity in a dose-dependent manner. On the other hand, the
      cytosolic enzyme can be rendered active in the presence of 1 microM 13
      hydroperoxyoctadecadienoic acid. In HEL cell homogenates, a partial translocation
      of the cytosolic enzyme to the membrane takes place in a Ca(2+)-dependent manner,
      resulting in an increase in membrane-associated 12-lipoxygenase activity and a
      concomitant decrease in cytosolic 12-lipoxygenase activity above 0.1 microM Ca2+.

PMID- 8295978
TI  - Different modes of endothelin-1 action in pressor response in vivo and pulmonary
      parenchymal contraction in vitro in the guinea pig.
AB  - Intravenously administered endothelin-1 (ET-1) (2 x 10(-11)-6 x 10(-10) mol/kg)
      induced dose-dependent pressor responses in anesthetized guinea pigs.
      Pretreatment with indomethacin (5 mg/kg, i.v.) or with a thromboxane
      A2/prostaglandin endoperoxide receptor antagonist, ONO-3708 (0.5 and 1.0 mg/kg,
      i.v.) significantly attenuated the pressor responses. ET-1 (10(-11)-10(-7) M)
      dose-dependently contracted guinea pig pulmonary parenchymal strips in vitro.
      However, neither pretreatment with indomethacin (10(-5) M) nor one with ONO-3708
      (10(-6) M and 10(-5) M) significantly affected the ET-1-induced guinea pig
      pulmonary parenchymal contraction in vitro. Moreover, pretreatment with a
      platelet activating factor receptor antagonist, CV-3988 (2 x 10(-5) M) did not
      significantly affect the contraction. Thus, in guinea pigs, the mechanism of ET-1
      induced pressor response in vivo mediated via cyclooxygenase-generated
      eicosanoid(s), possibly, thromboxane A2 is not identical to that of ET-1-induced
      contraction of pulmonary parenchymal strips in vitro.

PMID- 8295979
TI  - The "interleukin 1 receptor antagonist" is a partial agonist of prostaglandin
      synthesis by human decidual cells.
AB  - In many systems the interleukin-1 receptor antagonist opposes the effects of
      interleukin-1 beta. We considered that it might block interleukin-1 beta
      stimulated prostaglandin production from human decidual cells. Very high levels
      of interleukin-1 receptor antagonist (> 1000 pg/ml) had limited inhibitory
      effects on IL-1 beta-stimulated PGE2 synthesis, and lower levels of antagonist (<
      1000 pg/ml) increased the effects of IL-1 beta. Low concentrations of the
      antagonist alone (1-100 pg/ml) increased basal PGE2 production, whereas higher
      levels (10-100 ng/ml) had less effect. It seems, therefore, that in human decidua
      the "antagonist" is more accurately described as a partial agonist. It has been
      suggested that the IL-1 receptor antagonist could be used to inhibit decidual
      prostaglandin synthesis and thereby prevent preterm labor, but this report shows
      that caution should be exercised before using the receptor antagonist.

PMID- 8295980
TI  - Tumor necrosis factor alpha stimulates amnion prostaglandin biosynthesis
      primarily via an action on fatty acid cyclooxygenase.
AB  - The purpose of this study was to determine how tumor necrosis factor alpha (TNF
      alpha) stimulates prostaglandin E2 production in human amnion. Amnion cells were
      isolated from term placentae and grown to confluence in culture. Incubations were
      conducted in quadruplicate wells for 16 hours with TNF alpha and protein
      synthesis inhibitors cycloheximide and actinomycin D, or arachidonic acid,
      acetylsalicylic acid (ASA), or staurosporine or H7 which inhibit protein kinase C
      activity. Prostaglandin E2 (PGE2) was measured by radioimmunoassay and cellular
      protein determined. The stimulatory action of TNF alpha on amnion PGE2 production
      was blocked by protein synthesis inhibitors, and the addition of arachidonic acid
      always enhanced the stimulatory properties of TNF alpha. TNF alpha consistently
      induced more rapid recovery from ASA treatment, and protein kinase C inhibition
      attenuated the stimulatory effects of TNF alpha. These results suggest that the
      stimulatory action of TNF alpha on amnion PGE2 production is likely at the level
      of induction of fatty acid cyclooxygenase activity and is partially dependent
      upon activation of protein kinase C.

PMID- 8295981
TI  - Inhibition of adipose differentiation by 9 alpha, 11 beta-prostaglandin F2 alpha.
AB  - Prostaglandin F2 alpha (PGF2 alpha) is a potent adipose differentiation inhibitor
      for the adipogenic cell line 1246 and for adipocyte precursors in primary culture
      with an ED50 of 3 x 10(-8) M. In this paper, we examined the effect of several
      prostaglandins which have structural similarities with PGF2 alpha on the
      differentiation of 1246 cells and of adipocyte precursors in primary culture. The
      results show that only 9 alpha,11 beta-PGF2 alpha is as potent as PGF2 alpha to
      inhibit differentiation of adipocyte precursors in primary culture and of the
      adipogenic cell line 1246. In the presence of 9 alpha,11 beta-PGF2 alpha, the
      cells remained fibroblast-like, typical of undifferentiated adipocyte precursors.
      Triglyceride accumulation and increase of specific activity for glycerol-3
      phosphate dehydrogenase were inhibited. In addition, mRNA expression of early
      markers of differentiation such as lipoprotein lipase (LPL) and fatty acid
      binding protein (FAB) was decreased. The isomer 9 beta,11 alpha-PGF2 alpha and
      other PGF2 alpha derivatives were inactive. These results provide new information
      on the biological activity of 9 alpha,11 beta-PGF2 alpha as an inhibitor of
      adipose differentiation and about the structural characteristics of
      prostaglandins required for maintenance of a high adipose differentiation
      inhibitory effect.

PMID- 8295982
TI  - Ways of minimising hematopoietic damage induced by radiation and cytostatic drugs
      -the possible role of inhibitors.
AB  - Acute and chronic bone marrow toxicities are the major limiting factors in the
      treatment of cancer. They are related to two factors. (i) The first is a decrease
      in the number of hematopoietic stem cells and progenitors caused by both a lethal
      effect of cytotoxic agents on these cells and by differentiation of stem cells
      provoked by a feed-back mechanism, itself induced by the depletion of more mature
      marrow compartments. (ii) The second factor is a reduction in self-renewal
      capacity of stem cells, which is also related to both direct (mutation) and
      indirect (ageing of stem cell population) effects. Stimulators and inhibitors of
      bone marrow kinetics play a prominent role in the induction of damage and
      recovery patterns. Acute effects can be circumvented by an increase in the number
      of cell divisions in the more mature compartments. This amplification is enlarged
      by the administration of hemopoietic growth factors which enhance regeneration
      and shorten the duration of blood aplasia. However, these stimulators may
      contribute to the exhaustion of the stem cell pool and they may increase the
      severity of late effects. Protection against chronic effects is difficult;
      however, the ability to 'switch on' and 'switch off' proliferation opens new
      avenues which are currently being explored. In particular, inhibitors may protect
      stem cells against early and late damage by maintaining them in a quiescent state
      during a course of radiotherapy or chemotherapy. Several inhibitors of
      hematopoietic stem cell proliferation have been identified during the past 5
      years. AcSDKP (Seraspenide) was the first to be isolated and its protective
      effects against cytotoxic agents were described over a decade ago in mice. Its
      physiological role is now well established in mouse and man. Preliminary results
      of a Phase I-Phase II clinical trial strongly suggest that it may have a useful
      clinical role. Further research is necessary to assess the long-term protective
      effects of this new family of regulators.

PMID- 8295983
TI  - Accuracy in mantle field irradiations: irradiated volume and daily dose.
AB  - Accuracy of patient positioning and dose delivery in mantle field irradiations
      was investigated on 29 patients treated between August 1990 and December 1991.
      Patients were treated in two different centers, University Hospital St. Rafael in
      Leuven and Institut Gustave Roussy in Villejuif, where different techniques and
      procedures were used. Measurements were performed on 341 portal films and
      entrance doses were measured in 518 treatment set-ups. The impact of systematic
      errors occurring during treatment preparation and day-to-day variations on the
      accuracy of treatment execution were separately analysed. Daily reproducibility,
      defined as the deviation from the respective mean measured value for a treatment
      was demonstrated to be good for both the treated volume and the delivered dose
      and no difference between the two techniques was shown. Comparing the successive
      portal films of individual patients (reproducibility of a treatment, once it has
      started), only small day-to-day variations are found: the SD is 3.4 mm for
      craniocaudal movements and 2.6 mm for lateral movements. For dose delivery very
      narrow distributions are obtained with SDs of, respectively, 1.5% and 1.85% for
      the Leuven and the Villejuif group. This suggests that the position of the
      patient, which is often thought as the critical point in this complex set-up can
      be done in a very accurate way, regardless of the position used. To assess the
      global accuracy of the treatment, the actually treated volume and delivered dose
      were compared with the planned values. Apart from reproducibility this also takes
      into account the whole preparatory procedure between planning and the start of
      the therapy (first session).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295984
TI  - Chordoma: results of radiation therapy in eighteen patients.
AB  - Between 1975 and 1990, eighteen patients with a histologically proven diagnosis
      of chordoma were treated at our institution. All patients initially underwent a
      surgical procedure and were referred for irradiation due to residual disease or
      postsurgical relapse. The mean dose administered was 50.1 Gy (range, 29.9-64.8
      Gy). Eight patients were treated according to a hyperfractionated schedule. The
      overall actuarial 5-year survival and 5-year progression-free survival were 38%
      and 17%, respectively. The progression-free interval was longer for patients
      receiving doses greater than 48 Gy when compared with doses below 40 Gy
      (actuarial 5-year progression-free survival of 31 +/- 35% vs. 0%, respectively; p
      = 0.04). We conclude that in the treatment of chordoma, the administration of
      high radiation doses may increase the disease-free interval. The objective
      response and dose-response relationships were analyzed in twelve patients for
      whom sequential CT scans were available.

PMID- 8295985
TI  - Results of ruthenium irradiation of uveal melanoma.
AB  - The follow-up results are presented for the radiotherapeutic treatment of 49
      patients with uveal eye melanoma using ruthenium-106 (106Ru/106Rh) applicators.
      Graded doses were applied and the degree of regression was found to be correlated
      with the dose at the top of the tumour. Complete regression is found in 66% of
      the patients treated with a top dose above 150 Gy, in which case the initial
      tumour prominence diminishes in about three years to a stable disease or to a
      flat scar. At this dose a marginal increase in complications was observed as
      compared with lower dose groups. Useful vision could be preserved in 75% of the
      eyes.

PMID- 8295986
TI  - Possible leakage radiation during malfunctioning of a Sagittaire accelerator.
AB  - A non-fatal accident with a CGR-Sagittaire accelerator in the Dr Daniel den Hoed
      Cancer Center (DDHCC) in Rotterdam in 1988 is described. In a period with
      frequently occurring technical problems, a patient, undergoing fractionated
      treatment at this accelerator for prostatic cancer, developed severe skin
      reactions on the right half ventral part of thorax, head and upper arm. The skin
      reactions suggested an irradiation with a dose of up to 10-20 Gy, so it was
      likely that a radiation accident had occurred caused by leakage radiation. A
      number of experiments were performed in attempting to explain the estimated large
      dose rates of leakage radiation. Under rather extreme malfunctioning conditions,
      a high leakage dose rate (4 Gy/min) could be obtained during therapy use. This
      condition might have occurred during this period of technical difficulty.

PMID- 8295987
TI  - Radiation therapy in the unresectable cavernous hemangioma of the liver.
AB  - Hemangioma is the most common benign neoplasm of the liver, for which a 'wait and
      see' policy has been advised when it is small or without symptoms. Surgery is the
      treatment of choice of these tumors when marked symptomatology is present.
      However, some of these lesions cannot be excised due to their size, multiplicity,
      location or medical conditions. In these patients, radiotherapy has been reported
      to give good results with minor morbidity, suspending the tumor growth and
      decreasing the symptomatology. Seven symptomatic patients were treated with
      radiotherapy with a dose of 15-30 Gray in 15-22 fractions. Improvement of the
      quality of life was observed in all patients and the regression of the tumor
      volume was confirmed by computed tomography in five, with a follow-up ranging
      from 40 to 67 months.

PMID- 8295988
TI  - The effect of sequence and time interval between cyclophosphamide and total body
      irradiation on lung and bone marrow damage following bone marrow transplantation
      in mice.
AB  - The compromise between bone marrow killing effect and toxicity (mainly on the
      lungs) of the conditioning protocol used prior to bone marrow transplantation
      (BMT) determine to a great extent the final outcome. In search of an optimal
      balance between minimum lung damage and maximum bone marrow cell kill, we have
      tested the effect of varying the sequence and time interval between
      cyclophosphamide (CTX) and total body irradiation (TBI). CTX was administered
      almost concomitantly with TBI (i.e., 15 min before TBI) or 1-7 days before or
      after TBI. Lung damage was assessed by the lethality (LD) of the mice between day
      28 and day 180 after treatment, bone marrow damage by the LD of the mice between
      day 7 and day 28 after treatment and by the spleen colony assay. Mice chosen for
      lung damage testing were rescued from death due to bone marrow ablation by
      transplantation with syngeneic marrow cells. CTX potentiated radiation damage in
      both bone marrow and lungs. The effect on the bone marrow was greater when CTX
      was given after TBI than when given before TBI and this effect was significantly
      more than additive when the interval between the two agents was 3 days. Lung
      toxicity, on the other hand, was greater when CTX was given before TBI than when
      given after TBI. A therapeutic gain factor (TGF) was estimated by dividing the
      dose enhancement ratio (DEF) of bone marrow damage over the DEF of lung damage at
      all the time intervals studied. The results were consistently higher when CTX was
      given after TBI than when given before.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8295989
TI  - Radiation-induced astrocytic and microglial responses in mouse brain.
AB  - The aim of this study was to investigate the responses of astrocytes and
      microglia to whole brain irradiation. Levels of glial fibrillary acidic protein
      (GFAP), which is a marker for astrocytes, were measured by ELISA in irradiated
      brains taken at varying time points after irradiation. GFAP levels were increased
      between 120 and 180 days after single doses of 20-45 Gy radiation, but not after
      lower doses (2 or 8 Gy). The increases in GFAP levels were confirmed by Western
      blot analysis and immunohistochemical staining which showed that the number of
      GFAP-positive astrocytes was increased, as was their staining intensity.
      Coincidently with the increase in astrocyte staining, there was an increase in
      the number and the intensity of microglial cell staining for Mac I antigen.
      Autoradiography of brain tissue following in vivo administration of [3H]thymidine
      showed an increased number of labelled cells during the same time period. The
      radiation-induced astrocytic and microglial responses that follows brain
      irradiation is indicative of reactive gliosis and inflammation occurring during
      the latent period up to the onset of late radiation-induced injury. This gliosis
      increases with radiation dose. The possibility that gliosis may participate in
      modifying postirradiation injury in the brain is discussed.

PMID- 8295990
TI  - The delay before onset of accelerated tumour cell repopulation during
      radiotherapy: a direct maximum-likelihood analysis of a collection of worldwide
      tumour-control data.
AB  - The worldwide collection of control data for head and neck tumours presented by
      Withers et al. (Withers, H.R., Taylor, J.M.G. and Maciejewski, B. Acta Oncol. 27:
      131-146, 1988) was reanalysed using a model which includes an explicit lag phase
      before the onset of tumour clonogen repopulation. A direct maximum-likelihood
      approach was used and the methodology extended to include the computation of
      profile-likelihood confidence limits. A statistically significant (p = 0.02) lag
      of 29 days was obtained with 95% confidence limits covering the range 17-31 days.
      However, the confidence interval was disconnected, and excluded the period 21-23
      days. The analysis gave a time factor of 0.66 Gy/day. The mean values confirm the
      conclusions drawn by the original authors using a two-stage (indirect) method,
      and the values are similar to those calculated here for another data set
      comprising 496 patients (lag period = 26 (19-33) days). However, the data set
      itself is retrospective, and potentially subject to a number of biases. Therefore
      any clinical conclusions can only be tentative. A new feature of the methodology
      is the computation of profile-likelihood confidence limits and this will be
      useful in future direct analyses of clinical data of this type. The more usually
      computed normal approximation to the confidence limits have been shown to be
      inadequate in this analysis, and either profile-likelihood limits or likelihood
      ratio tests must be employed to determine the significance of the model
      parameters.

PMID- 8295991
TI  - Introduction to occupational psychiatry. Committee on Psychiatry in Industry
      Group for the Advancement of Psychiatry.

PMID- 8295992
TI  - [Magnetic resonance imaging in patients with sickle cell anemia].

PMID- 8295993
TI  - [Three-dimensional computerized modelling of anatomical structures by
      computerized tomography imaging].
AB  - The authors built an automatic CT-driven device by which 3D models of biologic
      structures can be obtained. Original bidimensional densitometric data are
      recorded on tape and transferred to a mechanical computer-driven arm capable of
      cutting polystyrene slices reproducing the original biologic structures by means
      of an original software. The aim of our research was to assess the feasibility of
      such a device from a practical point of view and to analyze and solve related
      problems, in order to use the experience thus gained to develop more complex
      systems. We deliberately set up a device both technologically advanced and simple
      to be used even by non-specifically trained operators. The system capabilities
      open new perspectives in many application fields, such as surgery (stereotactic
      procedures, the making of personalized prostheses, plastic surgery, procedures
      planning and simulation), treatment (stereotactic radiotherapy), diagnostics
      (stereotactic biopsy) and educational use.

PMID- 8295994
TI  - [Full computerization of a radiology service. A 5 years' experience at a
      centralized system].
AB  - Even though the problem of collecting and processing information is of paramount
      importance in any radiology department, the choice of the best information system
      -as for organization and effectiveness--largely depends on specific and different
      local situations and is therefore still largely debated. In the ULSS 18 in Veneto
      (Dolo, Venezia), all patients are referred to the only existing hospital
      radiology. Therefore, a central computer system has been be realized and used
      also by the radiology department, for completely computed procedures, since
      January 1, 1988. We describe the computer configuration of both the ULSS and the
      radiology department and report on our 5-year experience with full
      computerization within a central information system. As for department
      organization, any information system--with appropriate hardware and software--can
      be equivalent to others, since it largely contributes to both management
      (programming, booking, filing, accounting) and reporting (automatic reporting
      with memorized texts and/or voice recognition; reprinting; immediate correction
      at the video-terminal). Thanks to more rational exploitation of human and
      technological resources, any information system makes a radiology department more
      functional and efficient. However, some peculiarities of the central computer
      system must be stressed, as they allow: 1) to use pre-existing and updated
      patients files (unequivocal identification in the whole ULSS); 2) to gain access
      to the databanks of different specialties and to patients' clinical histories
      (complete data collected from many sources); 3) to intervene in booking and
      ticket collection centers with none of the relative loads; 4) to have no limits
      of memory, storage or speed for complex programs (automatic reporting also with
      the recognition of the dictating voice, accounting and statistical analyses,
      ecc.); 5) to profit by continually updated and fitted hardware and software, with
      the relative expenses and benefits shared by the whole ULSS. Within the
      possibilities given by a double role-ruled password, all different menus and
      programs are accessible from any video-terminal, even while other programs are
      running, thus allowing cost-effective hardware to be available in the radiology
      department.

PMID- 8295995
TI  - [Malpractice in breast imaging].

PMID- 8295996
TI  - [Animal experimentation in radiology. Objectives, organizational and ethical
      problems].
AB  - The contribution of biomedical sciences to the scientific breakthroughs in the
      last years has benefitted also by experiments on animals. As for diagnostic
      imaging, the use of new contrast media for angiography, CT and MRI makes it
      necessary, according to the law, to perform preliminary animal studies to test
      efficacy, pharmacokinetics and pharmacodynamics of the contrast agents.
      Experimental animal studies of clinically well-established contrast agents are
      also justified by the need to implement new imaging modalities. The close
      relationship between medical research and animal experimentation has awakened
      public opinion, as well as the researchers themselves, to the ethical and legal
      problems related to animal testing. This paper reports on the regulations which
      are currently in use in this field.

PMID- 8295997
TI  - [Microcrystal associated arthritis].

PMID- 8295998
TI  - [Bone cysts and continuous ambulatory peritoneal dialysis].
AB  - The clinical and radiologic patterns of amyloid osteoarthropathy in long-term
      hemodialysis patients are well known. However, few studies about the incidence of
      dialysis-associated amyloidosis in continuous ambulatory peritoneal dialysis
      (CAPD) patients have been published to date. In a series of 27 CAPD patients, the
      authors found bone cysts in 63.6% of cases, at the beginning of their dialysis
      treatment. After a mean follow-up period of 20.9 +/- 13.8 months, carpal bone
      cysts were seen in 70.4% of cases and clinical patterns worsened in 26.3% of
      patients. Therefore, CAPD does not prevent the development of dialysis-associated
      amyloidosis; prolonged uremic state and decreased diuresis seem to be the main
      pathogenetic factors of osteoarthropathy. The incidence and the evolution of bone
      lesions were related to the clinical data of this series and then compared with
      those of a group of hemodialysis patients. This study confirms that plain wrist
      films are a simple and useful method in the early detection and in the follow-up
      of amyloidosis-related disease.

PMID- 8295999
TI  - [Partial lesions of the posterior cruciate ligament of the knee: CT findings].
AB  - Posterior cruciate ligament (PCL) tears are more common than usually reported,
      especially in athletes. In the acute phase, PCL tears are particularly difficult
      to diagnose at clinical examination and may go unnoticed even to a skilled
      clinician because of concomitant lesions to other structures, of hematrhos or of
      strong muscular defense. The PCL is responsible for 95% of biomechanical knee
      stability and therefore plays a major role in the maintenance of joint
      congruence. In the long run, PCL tears cause posterolateral instability and an
      untimely development of degenerative changes, particularly at the patella. Site
      and grade of PCL tears must therefore be accurately assessed to plan the most
      appropriate treatment and to avoid the abuse of arthroscopy, toward improving
      cost-effectiveness for public health structures. Nowadays, CT of the knee joint
      is performed more frequently than MRI because the former is more easily
      available, in agreement with the current Italian economic choices in the field of
      public health. CT allows the accurate identification of complete and partial PCL
      tears. In our series (765 patients), PCL tears were more common than reported in
      the literature (9.5% vs 5%); moreover, PCL tears were always associated with
      lesions in other structures--e.g., anterior cruciate ligament, menisci. In
      conclusion, the CT demonstration of the knee joint, together with the knowledge
      of the physiopathologic relationships among different structures, allows better
      understanding of painful syndromes of the anterior joint compartment, which are
      particularly common in athletes. These syndromes are usually caused by a femoro
      patellar overload in people suffering from congenital ligament laxity, which may
      or may not be associated with abnormal knee morphotype--i.e., valgus, recurvatus.

PMID- 8296000
TI  - [Ultrasonography in the diagnosis and follow-up of hip pain in children].
AB  - Fifty-seven subjects aged 1.5-14 years (mean: 6.5; standard deviation: 3.3)
      complaining of hip pain and/or limp underwent clinical, US and radiologic
      examinations on admission and after variable time intervals. Twenty-eight of them
      were found to be affected with transient synovitis, 2 with rheumatic fever, 2
      with slipped capital femoral epiphysis and 5 with Legg-Calve-Perthes disease. The
      extant 20 subjects with normal US and X-ray findings were diagnosed as having
      irritable hip without effusion. No false-negative results were obtained from US
      (100% sensitivity), whereas X-ray provided false-negative results in 28 of 37
      patients with hip disorders other than irritable hip without effusion (24.3%
      sensitivity). No significant difference in the extent of hip joint effusion was
      found at US between the various groups. In the transient synovitis group, joint
      effusion was apparent on X-ray image in 3 of 28 patients, in whom the effusion
      was significantly more severe than in the extant 25 patients. Capsular joint
      effusion resolved more rapidly in transient synovitis than in Legg-Calve-Perthes
      disease. The patients with both rheumatic fever and transient synovitis exhibited
      the most rapid onset of symptoms. On the basis of our results, we suggest that
      each patient complaining of hip pain and/or limp should undergo US first and that
      X-rays be performed second, in selected cases only.

PMID- 8296001
TI  - [Mammographic screening of the health district 38, hospital of Gardone Val
      Trompia (Brescia - Lombardy). Results of the first 2 rounds].
AB  - The authors report the results of the first two rounds of a mammographic
      screening program by the Health District of Gardone Val Trompia (Brescia)
      including women 50 to 69 years old. 9,650 women were invited for round one and
      6,415 (66.5%) attended; 9,656 were invited for round two and 6,552 (67.8%)
      attended. Fifty-four cancers were found in round one (detection rate: 8.4/1000):
      11.1% of them were in situ carcinomas, 63% were T1 and 24.1% were T2 lesions, or
      higher. In round two, 32 lesions were detected (detection rate: 4.9/1000): 15.6%
      of them were in situ carcinomas, 78.1% were T1 and 3.2% were T2 lesions. In the
      positive cases axillary lymph nodes involvement was observed in 24.1% of cases in
      round one and was unknown in 27.8%, but the figures decreased to 6.2% and 9.4%,
      respectively, in round two. Effectiveness indicators were always observed.

PMID- 8296002
TI  - [Computerized tomography in the study of tuberculosis].
AB  - Twenty-five HIV-negative patients with proven tuberculosis were studied; 10 of
      them had had bacteriologic confirmation, 1 tuberculin conversion, 2 biopsy
      confirmation and in 12 cases ex juvantibus criteria had been followed. All
      patients underwent X-ray and CT exams of the chest which were useful for
      diagnosis, prognosis and treatment in 22/25 patients. CT yielded better results
      than conventional radiography in the following cases: miliary cases (1 CT
      positive case vs no positives at conventional X-rays), cavities (12 CT-positive
      cases vs 6 at conventional X-rays), bronchogenic spread (10 CT-positive cases vs
      7 at conventional X-ray), nodules (4 CT-positive cases vs 2 at conventional X
      rays), consolidations (5 CT-positive cases vs 1 at conventional X-rays),
      adenopathies (10 CT-positive cases vs 7 at conventional X-ray), extrapulmonary
      lesions (3 CT-positive cases vs no case at conventional X-ray). In 13 patients
      with negative sputum CT helped the diagnosis to be made. Chest radiography is
      currently the major exam for the first approach to tuberculosis. Nonetheless, CT
      yields valuable information when clinical signs or bacteriologic information are
      poor.

PMID- 8296003
TI  - [Bullous pneumopathy and spontaneous pneumothorax. Atypical radiologic patterns
      of Pneumocystis carinii pneumonia].
AB  - Pneumocystis carinii pneumonia (PCP) is certainly the most frequent opportunistic
      pulmonary infection in AIDS patients. Besides the conventional radiographic
      features demonstrating bilateral infiltrates and airspace consolidation, atypical
      radiologic patterns are reported in the literature, which are characterized by
      spontaneous pneumothorax and by the presence of bullae, cysts and areas of
      pulmonary cavitation. Forty consecutive PCP patients were investigated, ten of
      them presenting with atypical radiographic findings: 1 case of spontaneous
      pneumothorax with no evidence of bullae and 9 cases of bullous lung disease--5 of
      them complicated by spontaneous pneumothorax. Several pathogenetic hypotheses
      were considered; lesions evolution and the differential radiologic diagnosis were
      discussed. As for diagnosis, the value of chest CT scans is emphasized, together
      with that of HRCT which is extremely valuable to localize, characterize and
      evaluate bullous lesions and associated parenchymal signs.

PMID- 8296004
TI  - [Blunt hepatic and splenic trauma: indications for conservative treatment based
      on computerized tomography].
AB  - In this paper the authors try to define CT criteria for the evaluation of hepatic
      and splenic injuries in blunt abdominal traumas, to suggest and guide the
      nonoperative management of trauma in hemodynamically stable patients. The
      predictive value of CT on the outcome of the nonoperative treatment in adult
      patients with blunt hepatic and splenic trauma is trusted more and more also
      thanks to the good results of conservative management in similar injuries in
      pediatric patients. Thus, we reviewed 314 emergency abdominal CT scans performed
      in our center March 1990 to March 1992. The hepatic and splenic injuries detected
      on CT scans were evaluated according to a CT-based injury classification in
      grades, with a score reflecting progressive severity of lesions. Moreover, the
      presence of intraperitoneal hemorrhage was determined and quantified on the basis
      of a standard classification system. Of 314 cases, CT revealed blunt hepatic
      injury in 17 patients and blunt splenic injury in 38. We excluded the patients
      who exhibited, besides the hepatic or splenic injury, other severe visceral
      lesions which might need surgery. Nonoperative management was attempted in 9 of
      17 patients with hepatic injury and in 4 of 38 patients with splenic injury
      detected by CT; the scores given according to the above classification system
      were compared with the clinical outcome. The results indicate that hepatic
      injuries up to and including grade III, as assessed by CT, can be successfully
      managed without surgery in hemodynamically stable patients. As for splenic
      traumas, nonoperative management was attempted in a very small number of
      patients. Even though a case of grade-III splenic injury in our series was
      successfully treated without surgery, this may not be the rule, because the
      outcome of splenic injury and of intraperitoneal hemorrhage is often
      unpredictable.

PMID- 8296005
TI  - [Secondary hepatic hemochromatosis: diagnosis and quantification with 0.5 T
      magnetic resonance. Value and limitations].
AB  - Iron overload is a major cause of morbidity and mortality in thalassemia major
      patients. All chronic liver diseases may be associated with such endocrine
      symptoms as diabetes mellitus, testicular failure or hypothyroidism. We studied
      15 thalassemic patients (12 men and 3 women; age range: 10-50 years, mean: 22.5
      years). All patients received blood transfusions, but only some were treated with
      iron chelation. Seven patients were splenectomized. MRI was performed with an 0.5
      T superconducting magnet, using SE T1- and T2-weighted and IR sequences. We used
      these data with Bloch's equation to calculate T1 and T2 values. Quantitative
      analysis was made by calculating signal intensity and relaxation times in 8
      hepatic regions of interest: marked reduction in hepatic signal intensity and a
      negative relationship between T1 and serum ferritin (r = 0.646, p < 0.01) and
      between T2 and serum ferritin (r = 0.688, p < 0.01) were observed. Moreover, a
      negative relationship was found between hepatic signal intensity and aspartic
      aminotransferase (r = 0.524, p < 0.05). Our results confirm the value of MRI in
      the diagnosis and evaluation of hepatic iron overload but an accurate
      quantitative analysis can be made only when hepatic iron levels are between 1 and
      2 mg/g of liver. Even though it is below statistical significance, the negative
      relationship between signal intensity and aspartic aminotransferase suggests that
      hepatic hemochromatosis can influence pituitary-thyroid axis and interfere with
      peripheral hormone metabolism.

PMID- 8296006
TI  - [Errors of magnetic resonance in the diagnosis of small renal tumors].
AB  - MR examinations were performed on 16 patients with small (< 35 mm diameter) solid
      renal tumors previously diagnosed with US and/or CT. The study was aimed at
      assessing MR accuracy in the identification and characterization of this type of
      lesion. The studies were performed with a 0.5 T GE MR Max Plus unit, with no
      paramagnetic contrast medium administration. MRI detected the lesion in 15 cases
      (93.7%). In 3/15 patients (18.7%) the tumors had signal patterns similar to those
      of simple renal cysts--i.e., homogeneously hypointense on T1 and markedly
      hyperintense on T2-weighted images. In one patient (6.2%) MRI failed to detect
      the lesion. In the extant 12 cases the tumors were correctly demonstrated but had
      different signal patterns. On T1-weighted images 6 lesions were hypointense, 2
      hyperintense because of hemorrhagic content, and 4 exhibited poor contrast with
      the surrounding renal parenchyma. On T2-weighted images 4 lesions were
      inhomogeneously hyperintense, 3 were hypointense because of fibrosis or old blood
      content, and in 5 cases contrast between the tumor and the renal parenchyma was
      poor. The authors conclude that T1-weighted MR images, in a midfield MR unit, are
      more sensitive than T2-weighted images in identifying small renal tumors. MRI is
      less accurate in the evaluation of these lesions than CT and US. In particular,
      since small renal lesions may be misdiagnosed as simple cysts, the use of other
      imaging modalities--e.g., US and CT--is recommended if a renal cyst is first
      identified on MR images.

PMID- 8296007
TI  - [Functional magnetic resonance of Peyronie's disease in the chronic stable
      phase].
AB  - La Peyronie's disease (induratio penis plastica) is a degenerative process
      involving the penis, whose cause is still not fully explained. Adequate treatment
      requires the correct staging of La Peyronie's disease. Diagnostic imaging plays a
      major role after case history and clinics. Several imaging methods are used,
      including self-photography, plain radiography, CT, pharmaco-cavernosography,
      plain and duplex Doppler US. Enhanced MRI can be useful to correctly localize the
      plaques and to detect early changes in La Peyronie's disease, since the fibrous
      plaques with persistent inflammatory infiltration can be distinguished from the
      plaques in which inflammation has ceased. The diagnostic approach to La
      Peyronie's disease has been substantially modified by adding an examination
      during the erection induced by the intracavernosal injection of papaverine to the
      examination in the flaccid state. The authors report on the capabilities of
      unenhanced MRI after the intracavernosal injection of papaverine in steady
      chronic La Peyronie's disease. MRI was performed with an 0.5 T superconductive
      unit. Six patients (age range: 46-60 years, mean 52 years) who had been ill for
      about five years were studied. SE T1-weighted images and FS T2-weighted images
      were performed in both the flaccid and the erect states. Our results prove MR
      capabilities in both states in steady chronic La Peyronie's disease, which
      suggests MRI as the technique of choice for planning surgical treatment.

PMID- 8296008
TI  - [Renal angiomyolipomas: atypical aspects in ultrasonography and computerized
      tomography].
AB  - As a rule, renal angiomyolipomas (AML) present with characteristic patterns on US
      and CT images. However, in a limited number of cases US and CT findings are
      atypical, so that no diagnosis can be made on their basis. The authors reviewed
      their personal series of renal tumors and now report the US and CT findings of 5
      cases with atypical features on one or both examinations. Two patients had
      hyperechoic lesions with typical AML patterns, but no fatty densities were
      visible with CT. Both patients underwent surgery and histology which showed two
      AMLs with muscular and vascular components and very few fatty cells. Two cases
      were observed in patients with Bourneville disease. Even though the cases
      exhibited atypical features on US and CT images, the diagnosis was suspected on
      the basis of the well-known association of tuberous sclerosis with AML. One case
      presented with a complex cystic mass on US; CT showed a bleeding tumor. Even
      though no unquestionable diagnosis of AML could be made in this case, the
      hypothesis of a bleeding AML was considered in the differential diagnosis. Such
      atypical imaging features were related to low fatty content inside the lesion and
      to bleeding complications. Absent/low fatty component represented a cause of
      atypical lesion appearance on CT which showed a mass with soft-tissue density
      which could not be differentiated from a solid tumor. In these cases, AMLs
      remained typically hyperechoic on US images. Bleeding represented a cause of
      error mainly on US since the typical hyperechoic pattern was replaced by a iso
      hypoechoic pattern. CT is helpful in these cases because it shows both the
      bleeding and possible low-density fatty areas.

PMID- 8296009
TI  - [Percutaneous angioplasty of arterio-venous fistulae with Zijlstra catheters].
AB  - Brescia-Cimino arteriovenous fistulas are the most common vascular accesses in
      hemodialysis patients. Arterial blood pressure inside the vein and repeated
      punctures cause progressive sclerosis of the vessel wall and stenosis or
      occlusion are the final outcome. Percutaneous dilatation is an effective method
      to preserve arteriovenous fistulas function. From January 1991 through December
      1992, eleven dilatations were performed in 10 patients (7 women and 3 men, mean
      age: 55 years) using a Zijlstra dedicated catheter provided with multiple
      infusion holes, which allows long dilatation times and therefore progressive wall
      distention. A high-pressure balloon yields better results in case of stiff and
      diffuse stenosis. The immediate results of the maneuver were good in all
      patients. One acute thrombosis of the fistula was observed a few hours after the
      procedure, and a second dilatation was performed in a patient 8 months after the
      first one. Mean arteriovenous fistula patency time was 6 months. Finally, a
      critical review of the international literature on the subject is made and the
      value of dilatation in the treatment of fistula stenosis is reported; the
      necessity to use new dedicated catheters in also stressed.

PMID- 8296010
TI  - [Ultrasonography-guided alcohol injection in simple renal cysts. Long-term
      results].
AB  - The percutaneous treatment of simple renal cysts must be restricted to
      symptomatic lesions. It consists in a guided puncture, fluid aspiration and the
      injection of a sclerosing agent. The authors describe the procedure they
      followed, which has been made possible by technical progress. It consists in US
      guidance, a Trocar catheter drainage set and the injection of absolute alcohol.
      Moreover, the long-term results are reported of a retrospective study of 69/148
      treated patients who underwent one or more US exams 15 days to 5 years after the
      procedure. Eleven of 69 patients (15.9%) exhibited complete regression, 42 of 69
      (60.9%) had lesion relapse < 5 cm phi and 16 of 69 (23.2%) had > 5 cm relapse. On
      the whole, 53 (76.8%) positive results were obtained after the first treatment;
      positive results were obtained after the second treatment in 4 of 16 patients
      with > 5 cm relapse. US follow-up showed changes in the sizes of the relapsed
      cysts, which sometimes shrunk in the long run. All treated cysts reduced in
      volume; nevertheless, it would be useful to look for new sclerosing agents
      allowing a higher rate of complete regressions.

PMID- 8296011
TI  - [Temporary caval filters. Indications, problems and results].
AB  - The authors report their experience with the temporary placement of inferior vena
      caval filters to prevent pulmonary embolism in acute deep venous thrombosis
      patients. Twenty devices--6 Filcard and 4 Bruneau type--were positioned and left
      in situ over a time period ranging 4 to 14 days (mean: 9.8). In one patient the
      filter was positioned and no adjunctive medical therapy given to provide
      protection before nephrectomy; five patients were treated with i.v. heparin that
      provided no vein patency but prevented disease progression. Due to failure in
      positioning infusion guide catheters within the thrombus, four patients were
      submitted to fibrinolysis and heparin therapy: when the thrombus stabilized on
      angiographic images, heparin alone was administered and then followed by orally
      administered coumarin anticoagulants. In two cases partial thrombosis resolution
      was achieved, but with no significant improvement in patency rate. Ten patients
      underwent in situ fibrinolysis: six of them exhibited moderate improvement in
      femoroiliac axis patency and in three patients the inferior vena cava was
      successfully recanalized. No patient had any clinical evidence of pulmonary
      embolism. One case had cranial thrombus spread which was successfully treated
      with fibrinolysis. In our opinion, to control possible thrombotic involvement of
      the device, the patients candidate for temporary inferior vena caval filters must
      be easy to "manage" and exhibit no contraindications fibrinolysis and
      anticoagulant treatment.

PMID- 8296012
TI  - [Physics homogenization and the choice of screen-film combination in conventional
      thoracic radiography].
AB  - The homogenization of conventional chest radiographs is obtained with mechanical
      filtration of the X-ray beam and it allows opacity compensation of the different
      anatomical structures under examination; consequently, more pieces of diagnostic
      information on the mediastinum can be obtained. The authors used a mechanical
      device for equalization (Tau-Gil, Gilardoni SpA) with five different X-ray
      film/rare-earth screen combinations (3M Trimax) to investigate the following
      problems: a) choice of the best film-screen combination; b) results of the
      dosimetric comparison of filtered and non-filtered examinations; c) qualitative
      evaluation of equalization in terms of diagnostic information. One thousand
      analogic chest studies, 500 with and 500 without hard-filtering equalization,
      were performed with high-tension technique and statistically evaluated with a
      dedicated program. The authors concluded that: 1) the best qualitative results
      are obtained with GTU film/T6 screen combination, which seems to make the most
      satisfying compromise between sensitivity and spatial resolution and allows low X
      ray exposure to be combined with good diagnostic results; 2) dosimetric tests
      clearly show that in hard-filtered studies the average incident dose to the
      patient is 12% lower than that given with no filter. Particularly, skin and lung
      doses decrease, while mediastinum dose doubles to allow the simultaneous
      visualization of mediastinum and parenchyma; 3) a substantial difference exists
      between the frequencies of excellent, good and bad results in the comparative
      series (with and without equalization) for the evaluation of central chest areas,
      especially for mediastinum, retrocardiac region and carena. The overall rate of
      poor results was reduced by equalization, ranging 11.6% to 2.8% (mean: 6.3%) in
      equalized studies, and topping 64.2% (average: 35.5%) in non-equalized studies.
      Therefore, in the authors' experience, equalization with this type of mechanical
      device improves the depiction of the mediastinal region, with no significant
      imaging loss in lung parenchyma demonstration. Moreover, hard-filtering decreases
      average incident dose to the chest and skin-lung dose, increasing mediastinum
      dose to allow its correct demonstration.

PMID- 8296013
TI  - [The dose and quality program in mammography (DQM). Results of the study carried
      out in 20 Fruili-Venezia Giulia centers].
AB  - Recently, 20 breast centers in Friuli Venezia Giulia have been investigated for
      the mammography optimization program known as DQM (Dose and Quality in
      Mammography). This was the second trial, the first one dating 1987-1988 and
      including only 10 centers. The chosen parameters were evaluated by means of a
      performance phantom containing 15 details, a Victoreen 660 ionizing camera, a
      star pattern and several plexiglass phantoms of different thickness. Statistical
      methodological data were collected by means of a questionnaire. The results of
      the trial were communicated to each center as well as directions for future
      improvements. All centers were found to use mammographic equipment with a
      molybdenum anode and the film-screen combination; 18 center use grids daily,
      while 11 can perform direct radiographic magnification. Only 40% of the examined
      centers use a dedicated daylight printer. The overall quality of the radiographic
      image was seen to be acceptable, as 8 or more details of 15 hidden in the phantom
      were visualized, in 16 of 20 centers. The mean glandular dose was below the
      minimum threshold in all centers: in 45% of cases it was below 1.5 mGy. The
      setting of the automatic exposition control system was found to be poor,
      especially that of the adjustment related to breast thickness. Acceptability
      thresholds were met only by 31% of the examined centers (density variations <
      20%). Notwithstanding the identification of areas where improvements can be made
      also from a methodological point of view, we can conclude that the quality
      provided by regional breast centers is definitely adequate. Good image quality
      and acceptable doses were observed in 80% of the centers. The results are
      significant and encouraging when compared with those from the first DQM trial
      carried out in our region, which confirms the value of periodical quality
      programs.

PMID- 8296014
TI  - [Cephalometry and digital radiography. Technical note].
AB  - Conventional and digital lateral teleradiographs of the skull were performed on 6
      consecutive patients (3 men and 3 women). The study was aimed at comparing the
      diagnostic capabilities of the two imaging techniques to measure points and
      angles, as derived from different cephalometric analyses (see text for details).
      These variables were analyzed by three different operators: for both techniques,
      18 cephalometric tracings were made, including a total of 414 points and 36
      angles. Correlation coefficients between the two types of measurements (points
      and angles) were calculated; Wilcoxon's non-parametric test was also used. This
      study demonstrates digital radiography to be superior to conventional radiography
      to detect cephalometric landmarks, which is especially evident in the evaluation
      of the so-called "questionable" landmarks: the latter were 15 of 23 with
      conventional radiography and 9 of 23 with digital radiography. On the other hand,
      correlation coefficients and significance of the values of the considered angles
      were in close agreement with the two techniques. Therefore, its simultaneous
      demonstration of anatomical structures of different thickness--i.e., bone and
      soft tissues--and its lower exposure dose make digital radiography the diagnostic
      procedure of choice in cephalometrics, especially in the pediatric age, as well
      as in monitoring the patients.

PMID- 8296015
TI  - [Physiologic variability of jugular foramen dimensions. Critical reflections on
      the problems of clinico-radiologic differential diagnosis].

PMID- 8296016
TI  - [Post-traumatic osteolysis of the clavicle. Description of 2 cases].

PMID- 8296017
TI  - [Erosion of the external auditory canal in rheumatoid arthritis].

PMID- 8296018
TI  - [Non-invasive diagnosis of cardiac right-to-left shunt. Description of an unusual
      case].

PMID- 8296019
TI  - [Gas embolism of the portal venous system. Computerized tomography findings in 2
      cases].

PMID- 8296020
TI  - [Role of computerized tomography and lymphography in the diagnosis of chyluria.
      Description of 2 cases].

PMID- 8296021
TI  - [Non-invasive integrated diagnosis of Rendu-Osler disease with liver
      involvement].

PMID- 8296022
TI  - [Unusual case of gallbladder duplication diagnosed by ultrasonography].

PMID- 8296023
TI  - [Alkaline encrusted cystitis. Presentation of 2 cases].

PMID- 8296024
TI  - Investigating the generality of the delayed-prompt effect.
AB  - Two experiments were conducted in an attempt to replicate the findings of
      Touchette's classic 1971 experiment. The results obtained were more variable than
      those obtained by Touchette. Four of 34 subjects learned the Horizontal E
      discrimination without errors. Ten subjects preempted the red prompt stimulus
      erroneously. Twelve subjects failed to preempt. Among those who failed to
      preempt, at least six had not learned the target discrimination. There were also
      five subjects who failed to preempt who, on subsequent tests, demonstrated that
      they had learned the target discrimination. For these subjects, the onset of the
      prompt appeared to grant "permission to respond." An attempt is made to account
      for the differences in the current results and those of Touchette (1971). We also
      compare our results to the usually successful application of the delayed prompt
      to education and training problems. We note that the procedures used in these
      successful applications are often quite different from those in the original
      Touchette experiment and our own.

PMID- 8296025
TI  - Effects of a nutritional supplement on coprophagia: a study of three cases.
AB  - The cases of three individuals with profound mental retardation and long
      histories of coprophagia (ingestion of feces) were studied to determine if fecal
      material could be providing a nutrient that was unavailable from a standard
      institutional diet. In each case the individual was provided with a daily oral
      supplement of an "elemental diet," which, at twice the dose administered, would
      provide all the nutrients necessary for sustenance. The frequency of coprophagia
      was decreased in all three cases when they received the supplemental nutrients as
      compared to when they were maintained on a balanced institutional diet alone.

PMID- 8296026
TI  - Generalized identity matching to sample of two-dimensional forms in individuals
      with intellectual disabilities.
AB  - An assessment of identity matching to sample with two-dimensional forms was
      conducted with 44 subjects with moderate and severe intellectual disabilities.
      Identity matching that did not require conditional discriminative functions was
      tested first; subjects who passed that test were then tested on a conditional
      identity matching task. Tests for generalized identity matching were passed by 30
      of the 44 subjects. The 14 individuals who did not pass were given a further
      teaching assessment that sought to teach identity matching directly via standard
      teaching methods. Some subjects also received training on a series of simple
      discriminations taught by the same methods. Four additional subjects passed
      identity matching tests. Overall, generalized identity matching was demonstrated
      in 34 of 44 subjects, including 7 of 16 individuals with mental age (MA) scores
      of 3.0 years and below and 14 of 15 individuals with MA scores between 3.0 and
      5.0 years. Results with these two groups are much superior to those typically
      reported for individuals with comparable MA scores. The capacity for generalized
      performances requiring same/different judgments appears to have been
      substantially underestimated in this population, perhaps especially when the
      stimuli are two-dimensional, relatively abstract forms.

PMID- 8296027
TI  - Within-session patterns of self-injury as indicators of behavioral function.
AB  - Functional analysis assessment procedures have proven to be highly useful in
      identifying variables maintaining aberrant behavior like self-injury. When
      successful, assessments can lead to more effective treatment than when behavioral
      function is unknown. Because of practical limitations, not all clinicians can
      conduct extensive and thorough analyses prior to treatment implementation.
      Although relatively brief assessments have proven successful in a number of
      published studies, it is unclear under what conditions those assessments would
      match the results of a more extended analysis. This study examined a method for
      assessing the behavioral function of severe self-injury in four adult
      participants. For each participant, the initial assessment involved analyzing
      within-session trends and fluctuations in rates of self-injury by plotting the
      frequency within each minute of a session. The results of these analyses were
      then compared to a set of more traditional, longer-term functional analyses
      conducted with each participant. Results suggested that within-session analyses
      are viable procedures for the assessment of self-injury. Potential benefits of
      within-session analyses over other brief assessments and longer-term analyses are
      discussed.

PMID- 8296028
TI  - [Tuberculosis in the AIDS era].

PMID- 8296029
TI  - [Prevalence of HIV infection in France before the introduction of early
      treatment: estimation by back-calculation].
AB  - In order to estimate the cumulative number of adults infected with Human
      Immunodeficiency Virus (HIV) in France, the method of "backcalculation" was
      applied. This method assumes that the incubation period is constant over time,
      but the therapies administered since May 1987 among Acquired Immunodeficiency
      Syndrome (AIDS)-free HIV seropositive, extend the incubation period. It is
      obvious that if AIDS incidence counts beyond June 1987 are included in the
      backcalculation, this may lead to underestimation of the number of HIV infected
      subjects. For this reason we focused our study on estimates obtained from AIDS
      cases diagnosed until June 30, 1987. For each estimate we made the hypothesis of
      an average incubation time of 11 years (i.e. period between time of infection and
      onset of AIDS). We also examined the sensitivity of the results, with
      distributions of average incubation periods of 9 to 13 years. A "plausible range"
      (PR) was systematically calculated: it takes into account the imprecisions
      arising from model adjustment and from uncertainties regarding distribution of
      incubation period. Thus, the total number of infected people in France up to June
      30, 1987, was estimated at 142,300 (PR: 82,200 to 240,600), corresponding to an
      infection rate of 0.42 (PR: 0.24% to 0.71%) for the population between 15 and 59
      years of age. Estimations were also calculated according to sex for some
      transmission groups: homosexuals, injecting drug users and heterosexuals.

PMID- 8296030
TI  - [Analysis of delay in reporting of acquired immunodeficiency syndrome in France].
AB  - Reporting delays of AIDS cases in France could depend on such factors as
      geographic area of diagnosis, risk group or time of diagnosis. In order to
      identify the main sources of heterogeneity and to obtain realistic estimates of
      the number of diagnosed AIDS cases in France, we take into account these
      reporting co-factors by using a regression model. Results show significant
      variations between the 4 geographical areas considered (Ile-de-France, Provence
      Alpes-Cote d'Azur, 3 south-west regions, and the rest of metropolitan France).
      Reporting delay improved since 1986 in Ile-de-France and the 17 other areas of
      metropolitan France, with an earlier report of heterosexual cases. In the two
      other areas, no difference can be evidenced between reporting delays, nor
      improvement of such delay over time. The estimation discrepancies obtained are
      more noticeable over the last concerned year and will therefore have an impact on
      the epidemic growth previsions. The correction methods should therefore take into
      account these disparities in order to obtain more realistic predictions of the
      diagnosed AIDS cases.

PMID- 8296031
TI  - Suicide mortality in Italy: an update from 1955 to 1987.
AB  - Suicide mortality in Italy over the period 1955-87 has been analysed in terms of
      age-specific and age-standardised death certification rates, and using a log
      linear model to disentangle the effects of age, cohort of birth and calendar
      period at death. In males, the overall age-adjusted rate (on the World Standard
      population) was 8.6/100,000 in 1955-59, decreased to 6.7/100,000 in 1965-69, but
      steadily increased thereafter to reach 9.2/100,000 in 1985-87. In women, overall
      suicide mortality was 3.3/100,000 in 1955-59, decreased to 2.7/100,000 in 1965
      69, and increased to 3.2/100,000 in the late 1980's. The percent rise over the
      last two decades was approximately 35% for males and over 15% for females,
      corresponding to an excess of over 1,000 deaths per year. The rise in males was
      attributable to both a period and a cohort effect, and appreciable increases were
      evident among younger generations over most recent periods. For females, trends
      at younger ages were more favourable, and the recent increases were essentially
      on a period of death basis. Recent unfavourable trends are discussed in relation
      to increased unemployment in Italy during the early 1970's, and to changes in
      psychiatric care delivery, since a radical psychiatric reform was implemented in
      Italy in 1978. Differences of trends for males and females, and comparison with
      suicide trends in other Western countries, however, would not support any simple
      relationship between these factors and national suicide rates.

PMID- 8296032
TI  - Smoking habits in French adolescents.
AB  - A survey on adolescent smoking habits was carried out among 2,587 girls and boys,
      mostly aged between 11 and 16 and belonging to 16 schools representative of the
      'departement' of Rhone in France, in order to evaluate present smoking behaviour
      as well as estimate the influence of parents, friends and sociodemographic
      factors in acquiring or maintaining the habit. Students were surveyed in schools
      using a self-administered, anonymous questionnaire. Analysis was carried out
      using both the univariate and logistic methods, aiming at a precise
      quantification and description of the smoking habit, as well as an identification
      of predictors of smoking, separately for girls and boys, and also for triers
      only, occasional and regular smokers. Smoking regularly increases with age and
      from the age of 14 becomes slightly more prevalent among girls than boys. The
      influence of peer smoking (group of friends and best friend) seems stronger than
      parental smoking, although determinants of smoking differ moderately for girls
      and boys.

PMID- 8296033
TI  - [Evaluation of the screening strategy for lead poisoning in 1-to-3-year-old
      children monitored in maternal-child welfare centers in Paris].
AB  - A procedure for screening for lead poisoning was implemented since 1987 in the
      maternal and child health centers of 6 Paris "arrondissements". It relies on a
      screening of the children through environmental and clinical information. Our
      study aimed at evaluating this procedure and at estimating the prevalence of lead
      poisoning in the children aged 1 to 3 years old attending free maternal and child
      health centers in Paris. We did a cross-sectional survey of a sample of 512
      children. A questionnaire concerning each child's risk factors was answered by
      the paediatric nurses of the clinics. Potential lead poisoning cases were
      detected by capillary determining of free erythrocyte protoporphyrins (FEP).
      Blood lead level (PbB) was measured in children with FEP > or = 350 micrograms/l.
      The prevalence rate of lead poisoning was estimated at 1.9% +/- 1.7% for a PbB
      threshold > or = 250 micrograms/l and at 9.6% +/- 3.5% for a PbB threshold > or =
      150 micrograms/l. The detection procedure identified 4 children out of 5 with a
      PbB > or = 250 micrograms/l and 2 children out of 3 with a PbB > or = 150
      micrograms/l.

PMID- 8296034
TI  - Determinants of hysterectomy and oophorectomy in northern Italy.
AB  - We analysed determinants of hysterectomy and oophorectomy using data from
      hospital control subjects, interviewed in a large case-control study on risk
      factors for breast cancer, conducted since 1983 in the Greater Milan area, Italy.
      Out of the 2916 women interviewed 355 (12.2%) were hysterectomized. Mean age at
      hysterectomy was 52. The cumulative probability of hysterectomy was similar in
      women born during the periods from 1900 to 1909 and 1910 to 1919. It rose
      steadily in each subsequent cohort for all ages till the cohort born between 1930
      and 1939, then decreased in the cohort born between 1940 and 1949. The cumulative
      probability of hysterectomy by 60 years of age was 12.8% in women born between
      1900 and 1909, and of 9.8%, 16.7% and 22.0% respectively in subsequent cohorts.
      Concerning determinants of hysterectomy, we found no relation with education and
      parity. Among the 355 hysterectomized women, 178 (50.1%) underwent unilateral (40
      women) or bilateral (138 women) oophorectomy. The probability of oophorectomy was
      higher in more educated women. Compared with women who had had hysterectomy
      before the age of 45, those aged between 45 and 54 reported more frequently
      oophorectomy (odds ratio (OR): 1.5, 95% confidence interval (CI) from 0.9 to
      2.3), but the OR was only 0.8 in those aged 55 or more (95% CI from 0.3 to 2.2).
      We found no relation between menopausal status or cohort of birth and
      oophorectomy.

PMID- 8296035
TI  - [Human viruses in the coastal environment of a Croatian harbor].
AB  - The authors submit the results of a survey on the viral pollution of the costal
      environment in the vicinity of a Croatian harbour on the northern Adriatic sea.
      The presence of human viruses was established in 22% of the sea water samples,
      54% of the fluffy sediments samples, 44% of the sandy sediments samples and 26%
      of the batches of shell-fishes. Hepatitis A virus and rotavirus antigens
      determined by immuno-electro-osmophoresis made up 76.3% and 15.2% of the positive
      results respectively, whereas the coxsackieviruses, the echoviruses and the
      polioviruses isolated on cell culture made up 8.5% of the remaining results
      together. The analysis of several specimens of different nature taken
      simultaneously gave a better vision of the viral pollution.

PMID- 8296036
TI  - [Reduction in follow-up period of a study using criteria supplemental to death].
AB  - This work concerns the estimation of the follow-up period reduction for patients
      involved in a survival study when an auxiliary event is also used as an endpoint.
      An estimation procedure has been proposed using a surrogate criterion as an
      addition to the main endpoint criterion. This procedure is a two-stage study and
      enables us to estimate the survival function by using both criteria
      simultaneously. With a model of disease progression including the surrogate
      criterion as well as the main endpoint, simple calculations assess the gain in
      time with the two-stage procedure by comparison with a one-stage procedure. This
      gain in time, expressed in terms of a reduction of the follow-up period, depends
      on the prevalence of the surrogate criterion and its impact on survival. In the
      last part of this paper we discuss the advantages and disadvantages of such a
      procedure in common practice.

PMID- 8296037
TI  - [Serum alanine aminotransferase in blood donors: evaluation of various cut-off
      values].

PMID- 8296038
TI  - [Tuberculosis and HIV infection in France].

PMID- 8296039
TI  - [Trends in tuberculosis mortality in France].

PMID- 8296040
TI  - [Trends in tuberculosis in Western Europe].

PMID- 8296041
TI  - [Growth hormone and Creutzfeldt-Jakob disease].

PMID- 8296042
TI  - [Cavo-atrio-pulmonary anastomosis].

PMID- 8296043
TI  - [Heart transplantation in children].

PMID- 8296044
TI  - [Pediatric cardiology].

PMID- 8296045
TI  - [Echocardiography in pediatric cardiology].

PMID- 8296046
TI  - [Prenatal cardiologic diagnosis].

PMID- 8296047
TI  - [Interventional catheterization. Pulmonary valvuloplasty: angioplasty of
      pulmonary branches].

PMID- 8296048
TI  - [Interventional catheterization. Valvuloplasty of infantile congenital aortic
      stenosis. Review of its current status].

PMID- 8296049
TI  - [Interventional catheterization. Percutaneous closure of patent ductus
      arteriosus].

PMID- 8296050
TI  - [Interventional catheterization. Other congenital or surgical cardiovascular
      defects susceptible to occlusion with mechanical device].

PMID- 8296051
TI  - [Holter monitoring of heart arrhythmias and conduction disorders in children.
      Exercise test].

PMID- 8296052
TI  - [Diagnosis of heart arrhythmias. Electrophysiology].

PMID- 8296053
TI  - [Ablation versus surgery in the treatment of arrhythmias].

PMID- 8296054
TI  - [Anatomic correction of transposition of great vessels: Jatene].

PMID- 8296055
TI  - Current status of diagnostic cytology.

PMID- 8296056
TI  - The Munich nomenclature.

PMID- 8296057
TI  - The Bethesda system: the European perspective.

PMID- 8296058
TI  - Fluorescence microscopy for Pneumocystis carinii.

PMID- 8296059
TI  - Quality control in cytology.

PMID- 8296060
TI  - Who is a medical cytologist?

PMID- 8296061
TI  - Cytology training in the European community: European Community Training
      Programme in Cervical Cancer Screening.

PMID- 8296062
TI  - The Austrian regulation.

PMID- 8296063
TI  - The Swiss regulation for the specializations of cytopathology and gynecocytology.

PMID- 8296064
TI  - Diagnostic cytology in the United States.

PMID- 8296065
TI  - Cytotechnologists in Germany.

PMID- 8296066
TI  - Outlook for diagnostic cytology in Germany.

PMID- 8296067
TI  - Current status of diagnostic cytology in Germany.

PMID- 8296068
TI  - Tumor biology in diagnostic cytology: DNA cytometry in carcinomas of the bladder
      and prostate.
AB  - Quantitative measurements of nuclear DNA by flow cytometry have been used in the
      investigation of bladder and prostate carcinomas. The subdivision of tumors into
      diploid, tetraploid and aneuploid enables further characterization of
      morphologically defined tumors. Distinct differences in the distributions of
      ploidy of aneuploid grade 2 and grade 3 bladder carcinomas strongly suggest two
      different pathways of development of these gross chromosomally abnormal tumors.
      Significantly lower S-phase values of grade 2 tumors compared with grade 3 tumors
      of the same degree of ploidy enable the differentiation of these two tumor types.
      The proportion of S-phase cells is significantly related with the stage of
      invasiveness of bladder carcinomas. In prostate carcinomas, the exponential
      decrease of diploid tumor with tumor stage, the increase of tetraploid tumors to
      maximum at intermediate stages, and the exponential increase of aneuploid tumors
      with stages after some delay strongly support the concept of the continuous
      development of the prostate carcinoma according to a three-compartment system.
      Further support for this concept is gained by the study of repeated fine-needle
      aspirates of the tumor and the observation of coexisting diploid and aneuploid
      cell lines in the developing tumor. An adverse effect of hormone deprivation on
      composed tumors by elimination of androgen-dependent and outgrowth of androgen
      independent cell lines cannot be excluded.

PMID- 8296069
TI  - Cytodiagnosis of viral infections.

PMID- 8296070
TI  - Cytology of viral infections in gynecologic smears.

PMID- 8296071
TI  - Immunocytochemistry in diagnostic cytology.
AB  - As the decision for immunocytochemistry is usually made on the basis of findings
      in Papanicolaou-stained smears and uncovering of the smears takes time, the
      immunocytochemical results are often reported with some delay. But they are of
      clinical interest only if reported within a short time. Therefore,
      immunocytochemistry on cytologic preparations must be carefully organized. The
      decision for immunocytochemistry must be made before the mounting medium has
      completely hardened to keep the time of uncovering short. The method of
      immunocytochemistry should fulfill the following prerequisites: 1. Cell sampling
      and fixation should be easy to handle for the clinician who sends the specimen to
      the laboratory. 2. Unspecific background staining, especially in cytologic
      preparations rich in blood and protein, should not occur. 3. The immunostaining
      method should be applicable to all kinds of cytologic material, fixed and stained
      smears included. 4. The nuclear structure of tumor cells should not be destroyed
      by the immunocytochemical procedure so that tumor cells after incubation are
      clearly distinguishable from normal cells showing a similar reaction as the tumor
      cells. There has hitherto been no such all-round method fulfilling all these
      prerequisites since the properties of the antigenic epitopes of the cells and of
      the antibodies recognizing them are too heterogeneous. Therefore several methods
      have to be considered and a variety of technical aspects such as fixation,
      storage of cytologic material, properties of tinctorial stains, of antibodies and
      of the antigenic epitopes must be studied to find out the two or three standard
      methods which meet the requirements in most cases. We recommend the ABC method
      for Papanicolaou-stained smears and the APAAP method for demonstration of
      lymphocyte markers. The indication of immunocytochemistry in diagnostic cytology
      is restricted by the limited number of specimens. Therefore, the following rules
      have to be observed: 1. The conventional light-microscopic examination must have
      priority over the immunocytochemical examination. 2. The cytologic specimens
      assigned for immunocytochemical examination must have been adequately fixed and
      stored. 3. As the number of smears is limited, the immunocytochemical
      examinations must be carefully planned and restricted to the absolutely necessary
      incubations. If possible, an informative smear has to be spared for documentation
      and future training of cytologists and cytotechnicians. 4. Immunocytochemical
      examinations in cytology are only justified if the diagnostic problem can be
      clearly defined. 5. The panel of antibodies should be selected carefully so that
      the results may give an answer to alternative questions. At least two antibodies
      should be applied.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8296072
TI  - Nucleolar organizer region-associated proteins: a diagnostic tool in cytology?

PMID- 8296073
TI  - Automation in cytology.

PMID- 8296074
TI  - Sampling and processing in gynecological cytology.

PMID- 8296075
TI  - [MNSs system mother-newborn segregation distortions].
AB  - We present segregation distortions for the MNSs system and for the sex ratio
      found among 400 mother-newborn pairs, from the northern Area of Santiago and the
      middle-low and low socioeconomic strata. Three subsamples were taken: from the
      non private patients of the Clinical Hospital of the University of Chile; from
      the Hospital San Jose, a public hospital of this Area; controls of malformed
      newborns belonging to an international study from the Clinical Hospital of the
      University of Chile. In spite of the almost homogeneity of socioeconomic strata
      and area, the differences among these subsamples did not allow us to take them as
      only one sample. We found excess of heterozygous individuals for the MN locus,
      specially among mothers. Ss heterozygotes had a higher sex ratio than ss
      homozygotes. Several distortions could not be dealt with as having a regular
      pattern in the three subsamples. A possible technical error is discussed.

PMID- 8296076
TI  - [Variation of the diploid pattern in tissues used as normal controls of solid
      tumors: advantages and disadvantages of flow cytometric analysis of paraffin
      embedded tissues].
AB  - The aim of the present work was to study the factors that influence the variation
      of diploid patterns in 75 areas of histologically normal gastric tissue, located
      in surgically resected stomachs due to early gastric cancer. Each sample was used
      as a diploid reference of its respective tumoral area. Fifty five samples were
      embedded in formalin and 20 corresponded to fresh tissue. It was found that in
      the older tissues, the cellular debris increased, the localization channel of the
      peaks shifted to the left (lower than channel 60) and the peak shape was
      deformed, with an increase in the variation coefficient (around 6) and an
      elevation and lengthening of phase S. When fresh tissue was used, the first peak
      was localized around channel 60-70, with a significant reduction of cellular
      debris, a lower variation coefficient amplitude (2-5) and a phase S adhered to
      the basal line. Aiming to observe the influence of paraffin embedding over time,
      21 tissue samples originally assayed as fresh tissues, were reanalyzed one year
      later. The same alterations initially observed in old tissues were again noticed.
      According to these results, it is necessary to select adequate controls for flow
      cytometric analysis to obtain an adequate histogram interpretation, and specially
      to calculate the ADN index.

PMID- 8296077
TI  - [Comparative study of famotidine vs ranitidine in critically ill patients in
      mechanical ventilation].
AB  - Stress ulcers are frequent in critically ill patients. Gastric mucosa protection
      with antacids, H2 blockers or sucralphate decrease the incidence of stress ulcers
      and upper gastrointestinal bleeding but may have adverse effects. The present
      study compares the efficacy of continuous infusions of famotidine on gastric pH
      control and bleeding prevention in critically ill patients receiving mechanical
      ventilation. Fifty six patients (aged 55 +/- 22 years, 26 male) were randomly
      assigned to receive famotidine 40 mg/day (n = 27) or ranitidine 150 mg/day (n =
      29) during 5 days. Gastric pH was measured every 6 hours and when it was below 5,
      aluminum hydroxide (30 ml every 2 hours) was administered to obtain values over
      5. Patients receiving famotidine had higher mean gastric pH (6.3 +/- 0.2 and 93%
      of measurements over 5 vs 5.8 +/- 0.6 and 83% of measurements over 5 (p < 0.05),
      and required lower amounts of aluminum hydroxide (1.880 vs 2.770 ml). No patient
      had evidence of gastrointestinal bleeding and one had a mild psychomotor
      agitation. No other adverse reactions were observed. It is concluded that
      famotidine was more effective than ranitidine on gastric pH control in
      mechanically ventilated critically ill patients.

PMID- 8296078
TI  - [Correlation between serum globulin levels and hepatitis C virus antibody].
AB  - BACKGROUND: some studies have suggested that the elevation of serum globulins in
      patients with chronic autoimmune hepatitis, paraproteinemias and rheumatoid
      arthritis could affect the determination of false positive hepatitis C virus
      antibodies (anti-HCV). AIM: to study the relationship between positive anti-HCV
      and serum levels of globulins in patients with liver disease. PATIENTS AND
      METHODS: one hundred thirty one patients with liver disease, 49 alcoholic, 38
      cryptogenetic, 17 autoimmune and 27 with other causes, were studies prospectively
      measuring simultaneously anti-HCV and serum levels of total, gamma and immuno
      globulins (IgA, IgG and IgM). These levels were compared between anti-HCV
      positive and negative groups and correlated with the ratio between serum optical
      density/cutoff optical density of the anti HCV assay. RESULTS: Twenty eight
      patients (21.3%) were anti-HCV positive, no differences in serum globulins
      between these patients and anti-HCV negative patients and no correlations between
      serum globulins and anti-HCV optical densities were observed. CONCLUSIONS: the
      hypergamma-globulinemia observed in these patients with liver diseases would not
      be responsible for positive hepatitis C virus antibodies.

PMID- 8296079
TI  - [Percutaneous biliary endoprostheses. Clinical experience of 6 years].
AB  - The aim of this study was to assess the effectiveness and long term permeability
      of percutaneous biliary endoprostheses. Seventy three patients with biliary tract
      obstruction due to a primary malignant tumor (n = 60), lymph node metastases at
      the porta hepatis (n = 10) and benign stenosis of a biliary-enteric anastomosis
      (n = 3), were treated between 1985 and 1990. Plastic prostheses were installed in
      63 patients and metallic in 10. The procedure had a 30% incidence of
      complications. Thirty three percent of the prostheses remained patent until
      patient's death. In 15 and 40% of patients, signs of prosthesis obstruction were
      observed three and six months after installation respectively, bearing in mind a
      mean survival of 24 weeks. In 90% of patients there was a clinical and laboratory
      improvement. Mortality was 30% at 30 days in the group of patients with malignant
      diseases. It is concluded that the installation of percutaneous biliary
      endoprostheses is a relatively safe and well tolerated procedure, with a low
      incidence of complications or mortality and that allows an effective biliary
      decompression.

PMID- 8296080
TI  - [Renal scintigraphy with captopril in the evaluation of renovascular
      hypertension].
AB  - The administration of an angiotensin-converting enzyme (ACE) inhibitor
      transitorily reduces the GFR in a kidney with renal artery stenosis, effect that
      can be ascertained with scintigraphic studies using ACE inhibitors. We evaluated
      the clinical usefulness of captopril renography (CR) in the diagnosis of
      renovascular hypertension (RVH) in 51 hypertensive patients in which this
      diagnosis was suspected. All subjects underwent angiography and RVH was diagnosed
      when renal artery stenosis exceeded 60%, there was lateralization of renal vein
      renin or there was a concordant clinical outcome. Renography was performed 15
      minutes after Lasix administration, using Tc-99m DTPA, before and 60 minutes
      after the oral administration of 50 mg of captopril. The scintigraphic criteria
      for a positive test were a decreased split renal function, a delayed peak uptake,
      a decreased excretion of DTPA and a prolonged transit time. In three of 28
      patients in whom angiography discarded RVH, CR was positive. In the 23 patients
      with confirmed RVH, CR was positive in 10 of 12 with unilateral stenosis, in 3 of
      8 with bilateral stenosis and 1 of 3 with stenosis in a transplanted kidney. The
      overall sensitivity and specificity of the test for RVH was 60.9% and 89.2%
      respectively. There were no changes in blood pressure or adverse effects after
      captopril administration. We conclude that CR in RVH is useful to select patients
      for further studies (angiography) and to perform a functional interpretation of
      angiographic alterations.

PMID- 8296081
TI  - [Aluminum-related bone disease in chronic hemodialysis patients].
AB  - Plasma aluminum (pAl) was measured in 58 patients coming from three centers using
      different preparation of dialysis water: deionizer (29 patients), softener (16
      patients) and reverse osmosis (13 patients). Twenty five healthy subjects were
      used as controls. A deferoxamine test was performed to 11 of 19 patients with pAl
      between 40 and 200 micrograms/dl and a bone biopsy with double tetracycline
      staining was executed to 15 patients with pAl over 40 micrograms/dl. Mean pAl was
      9.5 +/- 1.7 micrograms/dl in controls and 34.3 +/- 6.1 169 +/- 27.8 and 50.8 +/-
      10.3 micrograms/dl in patients coming form centers using deionizers, softeners
      and reverse osmosis respectively. Seventy six percent of patients coming from
      centers using deionizers and 85% of patients coming from centers with reverse
      osmosis had pAl below 40 micrograms/dl and all had values below 200
      micrograms/dl. Plasma aluminum had a increase of over 200 micrograms/dl in 6 of
      11 patients in which the deferoxamine test was performed. Six patients had a
      positive staining for aluminum in bone biopsies (three with basal pAl over 200
      micrograms/dl and one with a increase in pAL after deferoxamine < 200
      micrograms/dl). Of these, 2 patients had a mixed osteodystrophy and 4 a low
      turnover bone disease. Centers with deionizers and reverse osmosis had very low
      aluminum levels in dialysis water and five of six patients with aluminum levels
      related bone disease came from the center using softener.

PMID- 8296082
TI  - [Rheumatoid arthritis. Therapeutic efficacy of methotrexate and its hepatotoxic
      effects].
AB  - The efficacy and toxicity (specially hepatic) of methotrexate in low doses (7.5
      mg/week) was prospectively assessed in 21 patients with rheumatoid arthritis
      refractory to treatment with gold or penicillamine, during two years. Three
      patients were prematurely withdrawn from the protocol. A fast and significant
      improvement of RA was observed during the first six months, which tapered
      thereafter. Erythrocyte sedimentation rate decreased from 51.5 +/- 20.1 to 27.7
      +/- 11.5 mm/h (p < 0.05). A rise in serum transaminases, always raising to less
      than twice the normal value, was observed in 75% of patients in some moment of
      the follow up. Hepatic scintigraphy did not show significant changes. Hepatic
      histological alterations were mild and no changes were observed after two years
      of treatment. The main secondary effects were moderate and transitory
      gastrointestinal and hematological disturbances. The prednisone dose was
      decreased from 6.8 +/- 2.6 to 4.8 +/- 1.9 mg/day at twelve months. There were no
      withdrawals due to drug toxicity. It is concluded that methotrexate proved to be
      efficacious in the treatment of rheumatoid arthritis refractory to conventional
      treatments. Its secondary effects, although frequent, were discrete and
      transitory and there were no changes in liver histology.

PMID- 8296083
TI  - [Susceptibility of Neisseria gonorrhoea strains].
AB  - The susceptibility of 45 strains of Neisseria gonorrhoea was studied measuring
      minimal inhibitory concentrations of five antimicrobials. Results show that 66.7%
      of strains are resistant to tetracycline and 11.2% to penicillin. All strains
      were susceptible to ciprofloxacin, ceftriaxone and cefotaxime. This results
      should prompt to perform surveillance in different areas of Santiago and to
      establish new therapeutic norms for the treatment of gonococcal infections.

PMID- 8296084
TI  - [New perspectives in the treatment of rheumatoid arthritis].
AB  - The medical treatment of Rheumatoid Arthritis (RA), is currently going through
      deep changes, stimulated by the findings that the usual sequential fashion of
      administering different drugs does not stop the course of the disease and that
      erosions develop even in the first year. Combination therapy, including
      immunosuppressants, are advocated early in the course of RA. The use of potent
      and potentially dangerous drugs should be given to the patients who are more
      likely to develop a more severe disease. Clinical and laboratory markers of
      severity might guide the treatment of these patients.

PMID- 8296085
TI  - [Congenital hepatic fibrosis: an uncommon cause of portal hypertension].
AB  - Congenital hepatic fibrosis is an autosomic recessive disease, manifested in
      children or in young adults by hematemesis due to rupture of esophageal varices.
      Bacterial cholangitis may occur in some patients. Early diagnosis and treatment
      with portosystemic anastomosis and/or antibiotics may lead to a long survival
      with a good quality of life. Diagnosis requires histologic confirmation: normal
      hepatic lobules are surrounded by broad fibrous bands, and an increased number of
      bile ducts is usually seen in the portal tracts. Liver function remains well
      preserved. This report consists of 3 patients: a 17-year-old woman, a 10-year-old
      boy and a 24-year-old woman who developed severe upper GI bleeding due to
      ruptured esophageal varices. The first two patients were successfully operated on
      using the Sugiura technique for portal decompression. Their current survival
      after surgery is 3 and 9 years, respectively, with normal physical examination
      and liver function tests. The third patient died shortly after admission, due to
      the concurrence of a severe suppurative cholangitis.

PMID- 8296086
TI  - [Hepatic angiosarcoma: report of 4 cases].
AB  - Hepatic angiosarcoma is an infrequent vascular liver tumor of high malignancy.
      Four patients (two males) are presented, in whom a histopathological study was
      performed. All patients died and in three a necropsy was executed.

PMID- 8296087
TI  - [The intestines, their role in the critical patient and the concept of bacterial
      translocation].
AB  - The gut is a central organ during critical illnesses that occur as a result of
      injuries or postoperative infections. After the successful treatment of shock,
      pulmonary and renal failure, a prolonged septic state emerges, frequently without
      apparent origin. An immunological host defense failure, associated with the
      intensive care support that fails to provide the essential amino acid glutamine
      to the gut, promotes a iatrogenic host invasion by microorganism or soilage by
      their toxins. This process is called "Bacterial Translocation". The increased
      permeability of the intestine, coupled with changes in intestinal flora, allows
      the bowel to serve as a reservoir of pathogens that can enter the portal and
      systemic circulations and fuel the ongoing septic process. Activating the hepatic
      reticuloendothelial system, bacterial translocation initiates the Multiple Organ
      Failure Syndrome. We discuss new therapeutic approaches derived from the
      aforementioned concepts.

PMID- 8296088
TI  - [The ethical challenge in psychiatry].
AB  - The historical reasons for the importance of ethical issues in medicine are
      revisited. An analysis of doctor-patient relationships in psychiatry allow us to
      conclude that the demand of an ethical reflection in this specialty is even more
      imperative. Specific ethical considerations are made about some customary
      activities of psychiatrists such as diagnosing, pharmacological prescription and
      psychotherapy. 1.- DIAGNOSIS: the facts that psychiatric diagnoses are based in
      conventions, are undemonstratable and that the patient's familial and work life
      depend on them, forces a careful management. 2.-Pharmacotherapy: due to the high
      proportion of secondary effects of pharmacological agents used in psychiatry 
      some of them irreversible- and the sort of human spirit manipulation that their
      use implicates, their indication must be painstaking. 3.- Psychotherapy: its
      legitimacy is the fundamental question, since the influence that a
      psychotherapist may get to have over his patients could be enormous. Aiming to
      find the real place of "healing by the word" in medicine, some Platonic texts are
      surveyed.

PMID- 8296089
TI  - [Analysis of the nutritional status of the population from Santiago].
AB  - The aim of this work was to analyze the nutrimental situation of people living in
      Santiago, reviewing the recent published information on this topic. There was
      profuse information about deficiency nutrimental problems among maternal and
      infantile groups, but fairly less in other age groups and about surplus disease.
      Considering food purchasing capacity, an important percentage of the population
      is located below the line of poverty. Child mortality has a low and decreasing
      rate and the general mortality structure shows a decline of infections causes.
      There is a low prevalence and degree of undernutrition among preschool children
      and a low proportion of low birth weight newborns. Instead, low stature affects a
      high proportion of school age children and its prevalence increases in puberal
      ages. Obesity predominates among adults and its risk factors are female sex, low
      stature and a low socio-economical level. Iron deficiency anemia is the most
      important specific deficiency. Outstanding features are the degree of communal
      development, a relatively better situation of Santiago compared with the national
      average and the lack of information and specific policies towards overfeeding
      related problems.

PMID- 8296090
TI  - [Work absenteeism in a mining company: trends in 1985-1988].
AB  - The magnitude of medical and non medical absenteeism among male workers
      performing rotative shifts in a high altitude mining company was studied. There
      was a general rate of absenteeism of 8.8 absent days per 100 labor days, which
      means that 31.8% of the total labor force was absent every month. Absenteeism due
      to medical causes correspond to a mean of 85% of total lost days during the four
      years of the study. Common diseases (digestive, respiratory, and osteo-muscular
      diseases, traumatisms and poisonings) give account 84.3% of these lost days.
      Among these, respiratory diseases had the higher prevalence and traumatisms and
      osteo-muscular diseases the higher severity (with values over 10 days off). The
      production areas and people working in shifts had the higher prevalences of
      medical absenteeism. The numbers of days off for medical causes almost doubled
      during the four year period and in 1988 represented 14% of all the salaries paid
      during the year. This increasing tendency was associated with a massive entrance
      to private health systems. It is concluded that the problem of medical
      absenteeism in this company is complex and growing and its attenuation requires
      preventive measures.

PMID- 8296091
TI  - [Homage to Dr. Guillermo C. Blest (1800-1884), founder of Chilean medicine].
AB  - William Blest M.D. graduated from Edinburgh Medical School in 1821 and was
      Director of the first course of medicine (1833) created in Chile after the
      independence. He arrived to Chile in 1823, when the rising Republic struggled to
      develop science, culture and its own identity as a nation. In 1826, he presented
      to the government of that time his "Observations over the actual state of
      medicine in Chile and a plan to improve it" and in 1828, an "Essay over the most
      common causes of diseases suffered in Santiago de Chile". The sanitary conditions
      were deplorable, hospitals were unhealthy barracks and there were only 9
      physicians, most of them foreigners. Outstanding was his address to the 11
      students of the 1833 course, that reflects love for the profession and contains
      valuable ethical concepts. Blest was a precursor of Public Health and founder of
      Chilean Medicine. He became a Chilean citizen in 1831 and was representative and
      Senator of the Republic. He formed a distinguished family and one of his sons,
      Alberto Blest Gana, was the most prominent chilean novelist of the nineteenth
      century.

PMID- 8296092
TI  - [Tolerance and immunogenicity of an oral dose of CVD 103-HgR, a live attenuated
      Vibrio cholerae 01 strain: a double-blind study of Chilean adults].
AB  - CVD 103-HgR is an attenuated, AB+, live, recombinant vaccine strain, developed by
      deletion of the toxA gen in a virulent Vibrio cholerae 01, Inada classical strain
      (569B). In phase II studies conducted to date, CVD 103-HgR has been well
      tolerated and immunogenic in volunteers from both industrialized countries and
      cholera-endemic areas. In this study of safety, immunogenicity and excretion, 81
      Chilean adults were randomly allocated to receive, in a double blind fashion, a
      single oral dose of 5 x 10(9) FU of CVD 103-HgR or placebo, (5 x 10(9) heat
      killed E. Coli K12 organisms), in 100 ml of buffered water. Side effects were
      assessed by daily visits to the participants. Immunogenicity, (vibriocidal
      seroconversion), was investigated in blood drawn before and on days 8 and 28
      after immunization, while stool cultures to assess excretion of the vaccine
      strain were performed on specimens obtained on days 1 and 7. None of the
      participants, (40 vaccinees and 41 placebo recipients), experienced untoward
      effects during 30 minutes of close surveillance after ingestion of the
      preparation; upon follow up, neither adverse events were more frequently reported
      by the vaccinees. 34/40 vaccinees, and 2/41 participants receiving placebo had a
      significant raise, (> = fourfold), in their vibriocidal titers; (85 vs 2%, p <
      0.001). The peak postimmunization geometric mean titer, (222), was ten fold
      higher than the baseline vibriocidal titer. The vaccine strain was recovered in
      stool cultures from 8 participants, one of them excreted the strain in both
      specimens. We conclude that CVD-103-HgR is safe and immunogenic in Chilean
      adults.

PMID- 8296093
TI  - [Chronic myeloid leukemia: cytogenetic and molecular study and its relationship
      with the disease course].
AB  - The aim of this study was to perform a cytogenetic and molecular study in
      patients with chronic myelogenous leukemia and to seek a possible relation
      between bcr gene break points and the clinical evolution of the disease. The
      cytogenetic study allowed to establish the presence of Ph chromosome and the
      molecular study localized the break point in bcr region of chromosome 22 using
      the Southern technique, hybridizing with bcr fragment derived probes bcr1 and
      bcr2. Forty eight patients were studied, 27 male (aged 46.5 years) and 21 female
      (aged 56). Forty seven patients were Ph +. A rearrangement in 3' bcr region was
      found in 25 patients and in 5' region in 23. During the follow up period 20
      patients developed a blast crisis or accelerated phase. In 11 of these the
      rearrangement was in region'3 and their chronic phase lasted a mean of 33.1
      months; in 9 the rearrangement was in region 5' and their chronic phase lasted
      44.1 months. There were no differences in event-free survival between those with
      rearrangement in region 3' or 5', however these was a tendency towards a longer
      chronic phase duration in those with 5' breaks. The lack of correlation between
      the location of break points and the evolution of the disease may be due to a
      selection of patients with a better evolution and the exclusion of those with a
      rapid progression to blast crisis or accelerated phase.

PMID- 8296094
TI  - [Cervix uteri cancer: determination of DNA content by means of cytophotometry].
AB  - ADN content was measured using cytofluorometry in 31 infiltrative uterine
      cervical carcinomas, using 22 routine cytologic cervical spreads (18 from
      archives) and 9 cellular spreads obtained from the fresh surgical specimen.
      Results were correlated to the clinical staging and morphological parameters of
      the tumor. Eight samples (25.8%) were diploid and 23 (74.2%) aneuploid. Women
      with diploid tumors were not significantly older. No correlation was found
      between ADN content and clinical staging, degree of histological differentiation,
      degree of cervical wall infiltration or the presence of vascular tumor
      permeations. All the cytological spreads were adequate for the cytofluorometric
      study. It is concluded that a high percentage of cervical carcinomas are
      aneuploid and that the present technique can be applied successfully to
      cytological samples.

PMID- 8296095
TI  - [Stomach and gallbladder cancer. Analysis of cell cycle phases by means of flow
      cytometry].
AB  - The characteristics of the different phases of cell cycle were analyzed in
      paraffin embedded samples of gall bladder cancer (n = 96) and gastric cancer (n =
      40). Computational programs that included Dean, Kosugi and manual methods were
      used. No differences in variation coefficients were observed between tumors with
      normal or aneuploid ADN content, with any of the employed methods. Histograms
      with variation coefficients over 10% were not considered. No differences were
      observed between the two forms of analysis of Kosugi's method; however there were
      differences between the manual method and Kosugi's and Dean's methods. The
      percentage of cells in G0/G1 phase varied between 74.1 and 81.5% according to the
      employed method. The obtained percentages with Kosugi's method with normal
      distribution were significantly lower in all the studied groups. These
      percentages fluctuated between 79.7 and 94.4% in tumors with normal ADN content
      and between 60.3 and 80.4% in tumors with abnormal ADN content. The proportion of
      cells in phase G2/M was lower and in phase S lower and more homogeneous among
      diploid compared to aneuploid tumors. These differences were observed only in
      primary tumors and not in metastases.

PMID- 8296096
TI  - [Hemodynamic and functional hepatic effects of isosorbide-5-monitrate in
      cirrhotic patients with portal hypertension].
AB  - Isosorbide 5-mononitrate reduces portal pressure in acute conditions. The aim of
      this work was to assess its effects and tolerance development after 30 days of
      use in alcoholic cirrhotic patients without history of variceal bleeding. Nine
      patients with portal hypertension (7 with esophageal varices) were studied.
      Hepatic and systemic hemodynamic parameters were measured in basal conditions,
      after one hour and after 30 days of treatment (40 mg b i d). One patient was lost
      from control at 2 weeks. In the total group, portal pressure decreased from 15.1
      +/- 3.7 mm Hg to 12.1 +/- 5 at one hour and 11.3 +/- 5.5 mm Hg at 30 days (p <
      0.002). In two patients, portal pressure was not modified. Portal blood flow
      increased significantly at one hour in the 7 responder patients. Hepatic blood
      flow (indocyanine green clearance) was not modified; thus, estimated hepatic
      resistance decreases in both periods. Intrinsic indocyanine green clearance (a
      measure of hepatic function) did not change in any period. Systemic blood
      pressure decreased and cardiac rate increased only after one hour. The fall in
      portal pressure did not correlate with changes in portal or hepatic blood flow.
      It is concluded that isosorbide 5-mononitrate decreased portal pressure in 7 out
      of nine patients, even after 30 days of treatment, without untoward effects over
      hepatic function or perfusion.

PMID- 8296097
TI  - [Determination of DNA content by means of cytophotometry. Technical and
      methodological considerations and its application in tumor pathology].
AB  - The cytofluorometric determination of ADN content in tumoral cells from 33 tumors
      is reported. Twenty five epithelial (2 benign and 23 malignant) and 8 non
      epithelial tumors (1 benign and 7 malignant) were studied. All the benign tumors
      had a normal ADN content (2c); on the other hand, 65% of malignant tumors had an
      abnormal ADN content. All non epithelial malignant tumors were aneuploid. Among
      aneuploid tissues, epithelial tumors were frequently tetraploid (4c) and non
      epithelial tumors were frequently polyploid 6c, 8c, 12c). It is concluded that
      this technique gives valuable information about the biological characteristics of
      tumoral cells and that its results could be incorporated to the routine
      anatomopathological study of tumoral lesions.

PMID- 8296098
TI  - [Left-handedness and diabetes mellitus of autoimmune origin].
AB  - A controversial theory postulates that there is an association between left
      handedness and immune and speech disorders. There are reports of increased
      frequency of left handedness in type I diabetic patients. The aim of this study
      was to compare 65 type I diabetics, 65 type II diabetics and 130 normal controls
      using a 7 item questionnaire for handedness. No differences were found for strong
      left handedness. However the frequency of strong right handedness decreased
      significantly from controls to type II diabetics and type I diabetics. Since less
      intense right handedness is not the same as left handedness, it is concluded that
      the theory is not supported by the present findings.

PMID- 8296099
TI  - [Autoimmune thyroid pathology of pregnancy and puerperium. Prevalence in a zone
      of endemic goiter and its impact on the newborn].
AB  - The aim of this work was to study the prevalence of thyroid disease in pregnant
      and puerperal women and newborns in Pirque (Chile) and its possible relation to
      iodine intake or autoimmune disease. Two hundred twenty eight women with 13.4 +/-
      3.4 weeks of pregnancy were examined initially and in 223, laboratory tests were
      performed. Goiter was found in 107 women. Although all women were euthyroid,
      those with goiter had higher serum levels of T3 and T4. Nineteen women had
      positive anti-thyroid antibodies and urinary iodine excretion was > 100
      micrograms/g creatinine in 87.2%. Within 2 and 57 weeks after delivery (mean 13.5
      weeks), 183 women were reexamined and in 175 laboratory tests were performed.
      Serum T3 continued to be higher in those with goiter. Fifteen women with positive
      anti-thyroid antibodies during pregnancy continued to have positive titres; of
      these, two had a post partum thyroiditis and one a graves disease. Two hundred
      three newborns were examined and no one had goiter or elevated TSH. It is
      concluded that there is a high frequency of goiter among pregnant and puerperal
      women from Pirque, that iodine intake is normal and that there is a low frequency
      of post partum thyroiditis.

PMID- 8296100
TI  - [Antimicrobial activity of amoxicillin versus amoxicillin/clavulanic acids. In
      vitro study against S aureus, H influenzae and A baumanii strains].
AB  - The aim of this study was to compare in vitro activity, measuring minimal
      inhibitory concentration, of amoxicillin or its combination with clavulanic acid
      against 109 strains of Acinetobacter baumanii, 104 strains of Hemophilus
      influenzae and 94 strains of Staphylococcus aureus. All these were obtained from
      different hospitals of the Santiago Metropolitan Region. Amoxicillin-clavulanic
      acid association did not improve the activity of amoxicillin against
      Acinetobacter. The association was not active against methicillin resistant
      strains of S aureus; instead, it significantly increased the activity of
      amoxicillin against methicillin susceptible strains. All the H influenzae strains
      were susceptible to the combination.

PMID- 8296101
TI  - [Cryptosporidium parvum in patients with chronic diarrhea and AIDS: diagnosis by
      means of indirect immunofluorescence with monoclonal antibodies].
AB  - The diagnosis of cryptosporidiosis is difficult when oocyst elimination is poor
      as occurs in AIDS patients. Aiming to improve the diagnosis, 144 fecal samples
      coming from AIDS patients with diarrhea, were studied using indirect
      immunofluorescence with anti-Cryptosporidium monoclonal antibodies. The results
      were compared with Ziehl Neelsen and safranine stainings. Twenty three samples
      (15.9%) were positive for Cryptosporidium with at least one of the three methods.
      Sensitivities were 78.3% for immunofluorescence, 86.9% for Ziehl Neelsen and 91.3
      for safranine stainings. The specificity of the three methods was 100%. It is
      concluded that immunofluorescence does not improve the diagnostic accuracy of
      cryptosporidiosis and its high cost precludes its use in routine laboratories.

PMID- 8296102
TI  - [Laparoscopic nephrectomy: report of 2 cases].
AB  - Laparoscopic surgery has become very popular in general surgery. Its most
      significant advantages for patients are a better postoperative comfort and fast
      return to work. We report two young female patients with a gynecologic cancer in
      whom a laparoscopic nephrectomy was performed. The surgical procedure and the
      post operative recovery were uneventful. These promising results show that
      laparoscopic surgery is applicable in traditional urologic procedures.

PMID- 8296103
TI  - [General practice: a theme in search of clarity].
AB  - Specialization is a consequence of the progress in knowledge and technology, and
      is essential to increase medical knowledge. Culturally, the population
      increasingly aspires to be attended by a specialist. On the other hand,
      generalism is necessary to protect the unitary focus on the sick patient, to
      mitigate the increasing cost of medicine and to avoid the increasing
      dehumanization of medical practice. The condition of generalist is not synonym of
      general practitioner and may be applied to internists or pediatricians with ample
      knowledge and diagnostic skills based more in medical interview and physical
      examination than in the sophisticated laboratory. Specialties have clearly
      defined fields of knowledge and action, have well established training programs
      and are culturally accepted, not so general medicine. In Chile, a significant
      number of trained general practitioners has not been attained, in spite of the
      existence of training programs since more than 20 years. Outpatient care (primary
      care in the language of health planners) may be undertaken by general
      practitioners but also, and perhaps with better efficiency, by general internists
      and pediatricians. The use of ones or others will depend on the geographic
      location (urban, suburban or rural), on the available physicians and the
      communication facilities with better developed medical centers. Within this line
      of thinking, the Faculty of Medicine of the University of Chile is studying a
      reform of medical curriculum, rotating internship and residency programs.

PMID- 8296104
TI  - [Biliary surgery mortality in Chile in 1990. Cooperative study in 17 hospitals].
AB  - A survey about surgical procedures performed in 1990 was answered by 17 surgical
      services. With these data the operative mortality of biliary surgery was
      analyzed. During 1990, 39,643 patients were subjected to major surgery of which
      9,654 (24.3%) corresponded to benign biliary tract diseases. Forty nine percent
      of patients had chronic cholecystitis, 36% acute cholecystitis and 16%
      choledocholithiasis. Global mortality of these procedures was 0.58% and
      mortalities for chronic cholecystitis, acute cholecystitis and
      choledocholithiasis were 0.06, 0.6 and 2% respectively. These numbers increased
      significantly in patients over 60 years old, are lower than those reported 10
      years ago and could be useful as "gold standards" for laparoscopic
      cholecystectomy.

PMID- 8296105
TI  - [Perception of patients from rural areas on referral resolution].
AB  - Eighty two patients from two public rural outpatient clinics were interviewed
      about referrals requested during June 1991, the unresolved proportion after six
      months, the alternative ways used to solve the health problems and their
      perception about this issue. A total of 95 referrals were requested in June in
      these clinics (4 every 100 consultations) and information about 85 was obtained.
      The frequency varies from 10% in the women's program, most of the referrals are
      directed to surgery, respiratory diseases and dermatology, in the adult's
      program, to radiology, gastroenterology and a wide variety of specialties. Six
      months later almost all the referrals had an appointment at the reference
      hospital. In spite of this, 20 patients did not receive the information and five
      sought a solution with private physicians. Of the 65 remaining patients, 12.3%
      lost their appointment due to diverse reasons such as preferring private
      physicians, oblivion or lack of money. Fifty seven patients went to the reference
      hospital. Thirty eight percent of these felt that their health problem had not
      been solved at the moment of the study, because they were still in treatment,
      were waiting a bed in surgery, the results of some laboratory tests were delayed
      or they perceived bad treatment. It is concluded that only half of the patients
      referred to specialists, felt that their health problem had been solved six
      months later.

PMID- 8296106
TI  - [Latin America: reasons for hope].
AB  - According to official figures, Latin America is almost an empty continent. The
      low population density, the decrease in population growth, the low use of the
      land and the improvement in the availability of food, health and education
      indexes, point to the fact that restrictive politics in population growth are not
      of interest to this region. On the contrary, an increase in population density is
      important in the development of this new civilization. In order to avoid the
      defects found in some industrialized countries, the anthropocetrism has to be
      linked to reality which is transcendent and has God as his foundation.

PMID- 8296107
TI  - [The "protomedicat" in the kingdom of Chile: the first independent court (1786)].
AB  - This work is part of a study that analyzes the performance and significance of
      protomedicato during the colonial period in Chile. The Royal protomedicus is a
      medical term for "physician in chief". The documents that were contemporarily
      generated with the event and the general secondary bibliography about the medical
      profession in Chile have been analyzed. All this historiographical material is
      mainly kept at the National Archives of Chile. Along the manuscript, the arduous
      task of the sanitary authorities of the moment is made evident. They struggled to
      obtain a court, that was considered essential to improve the Kingdom's health.
      However, in spite of their efforts, they were not rewarded promptly and had to
      wait four years to obtain some results. The slowness of the process was a
      consequence of the institutions ineffectiveness and huge bureaucracy of that
      times and not due to the distance between the Kingdom of Chile and the
      Metropolis.

PMID- 8296108
TI  - Distribution-free fitting of logit models with random effects for repeated
      categorical responses.
AB  - This article discusses random effects models for within-subject comparisons of
      repeated responses on the same categorical scale. The models account for the
      correlation that normally occurs between repeated responses. The standard way of
      fitting such models maximizes the marginal likelihood after integrating with
      respect to a distribution for the random effect. An alternative non-parametric
      approach does not assume a distributional form for the random effects. Recent
      literature shows that for certain simple logit models, this approach yields
      essentially the same model parameter estimates as conditional maximum likelihood.
      Moreover, these estimates also result from fitting corresponding quasi-symmetric
      log-linear models. For simple data sets in which primary interest relates to
      subject-specific comparisons of the repeated responses, one can easily obtain the
      estimates with standard software for log-linear models. Examples include data
      from crossover designs and from comparisons of treatment and control groups
      regarding the change between baseline and follow-up observations.

PMID- 8296109
TI  - Controlling for a confounder monotonically related to exposure by means of
      isotonic quantile regression.
AB  - We present a new approach to evaluating the effect of a continuous exposure
      factor when that factor increases with a covariate (for example, age) which is
      regarded as a potential confounder. The basic idea is to estimate, as functions
      of the covariate, some selected quantiles of the exposure distribution, under the
      assumption that the dependence of each quantile on the covariate is monotonic.
      The resulting estimates are then used to divide the data into different exposure
      categories. This method of categorizing the data implies that the covariate
      distribution will be almost the same in each exposure group. We illustrate the
      approach with a study of blood pressure and cardiovascular mortality.

PMID- 8296110
TI  - Two-stage sampling in pharmaceutical applications.
AB  - In the pharmaceutical industry, some tests for quality assurance before, during
      and after the manufacture of a drug product involve a two-stage sampling
      technique. We propose statistical testing procedures in a two-stage sampling
      problem with large within-class sample sizes. We also derive a two-stage sampling
      plan by minimizing the expected squared volume (or the generalized variance) of
      the confidence region related to the test. We present two examples to illustrate
      the proposed methods.

PMID- 8296111
TI  - Sample sizes for event rate equivalence trials using prior information.
AB  - Trials for demonstrating the 'equivalence' of active standard and test treatments
      generally require large sample sizes that depend on the definition of
      'equivalence' and the overall event rate when the outcome is incidence of an
      event such as mortality. The planning of sample sizes for such trials requires
      specification of a value for the overall event rate. This value often will
      reflect the outcomes of previous trials of the standard treatment, and is subject
      to uncertainty that needs some accommodation, to protect against an inadequate
      sample. Bayes and Empirical Bayes methods can be used to incorporate information
      from one or more previous trials into the sample size calculation when
      equivalence means high confidence that the event rate ratio is less than some
      specified value.

PMID- 8296112
TI  - An algorithm for robust non-linear analysis of radioimmunoassays and other
      bioassays.
AB  - The four-parameter logistic function is an appropriate model for many types of
      bioassays that have continuous response variables, such as radioimmunoassays. By
      modelling the variance of replicates in an assay, one can modify the usual
      parameter estimation techniques (for example, Gauss-Newton or Marquardt
      Levenberg) to produce parameter estimates for the standard curve that are robust
      against outlying observations. This article describes the computation of robust
      (M-) estimates for the parameters of the four-parameter logistic function. It
      describes techniques for modelling the variance structure of the replicates,
      modifications to the usual iterative algorithms for parameter estimation in non
      linear models, and a formula for inverse confidence intervals. To demonstrate the
      algorithm, the article presents examples where the robustly estimated four
      parameter logistic model is compared with the logit-log and four-parameter
      logistic models with least-squares estimates.

PMID- 8296113
TI  - Testing concomitancy between two physiological pulse series.
AB  - Statistical methods for detecting synchronization of onsets of two physiological
      events, such as concomitant releases of prolactin (PRL) and luteinizing hormone
      (LH), are studied in this paper. Usually, the two events are measured regularly
      and simultaneously and the onset times are then determined by the changes in the
      values of the measurements. Owing to difficulties in determining the exact onset
      times, a leeway is allowed for counting the onset synchronizations in most
      physiological studies. Using such a relaxed definition of synchronization and
      needing to allow for a recovery time between two episodes make the traditional
      hypergeometric test of concomitance inappropriate. Based on a truncated geometric
      inter-arrival distribution, Clifton et al. have used simulation to construct a
      table of critical values for performing tests of significance of the observed
      number of coincidences in a series of 73 measurements. In this paper, the
      conditions under which their method can be used are examined from a statistical
      point of view. Methods for testing cases not covered by Clifton et al. are also
      described.

PMID- 8296114
TI  - [What is your diagnosis? Seropositive chronic polyarthritis].

PMID- 8296115
TI  - [The process of accepting a chronic disease. What is the role of caregivers in
      management of these patients?].
AB  - Occurrence of a chronic disease means to the patient the loss of his accustomed
      state of health. That is what a newly diagnosed diabetic patient experiences,
      when he is confronted with the necessity for a perpetual treatment in order to
      keep his blood sugar levels as normal as possible. Furthermore, this disease may
      induce severe secondary complications because adjustment is difficult. Ability
      and will-power to care for himself depend on the degree of acceptance of the
      disease by the patient himself. This implicates a period of sorrow,
      characteristic phases of which have been identified and described by several
      authors. The relation between physician and patient plays an important role in
      this process. The physician should not only recognize the emotional reactions of
      his patient but also respond adequately.

PMID- 8296116
TI  - [How can compliance be ameliorated in diabetic patients?].
AB  - The compliance of diabetic patients is very poor. In addition to the knowledge of
      the various stages of acceptance of the disease as described by A. Lacroix in
      this journal, it is necessary to learn more about the patient's personality. In
      this article, four different personalities are proposed using the test "Persona"
      (Polymanagement SA, Geneva) in order to have the correct choice of therapy,
      corresponding to the personality. We hope that in the long term, by using this
      test, therapeutic compliance for the diabetic patients will be improved.

PMID- 8296117
TI  - [Compliance to therapy in daily practice: the case of immuno-allergic diseases].
AB  - The importance of patient compliance with pharmacotherapy has nowadays gained
      better acceptance. Compliance is considered by manufacturers of drugs who
      continue to propose simpler regimens. It is also of interest to clinical
      investigators because it may affect the outcome of every therapeutic study.
      Finally it has to be considered by all those who are concerned about education of
      practitioners because it touches essential characteristics of the relation
      between physician and patient.

PMID- 8296118
TI  - [Compliance to therapy in daily practice--rheumatologic diseases].
AB  - An insufficient compliance is regularly observed in 30% of outpatients. In
      chronic rheumatic diseases such as rheumatoid arthritis a poor compliance is
      often associated with alleviation of symptoms whereas symptomatic patients tend
      to take their medication more regularly. Drug abuse, mainly corticosteroids, can
      often not be avoided. The latter may 'particularly in women' lead to osteoporosis
      with subsequent fractures. In patients with fibrositis compliance is often a poor
      because of digestive problems associated with NSAIDs and the bad response to
      drugs and adjuvant therapies.

PMID- 8296119
TI  - [Non-compliant drug taking in elderly subjects].
AB  - Particular consequences of a poor therapeutic compliance by elderly patients are
      discussed in the context of three selected case reports. They comprise: dosage
      errors, discontinuation of therapy (also transient), neglecting of time schedule
      or rhythm of intake, concomitant therapies. This lacking therapeutic compliance
      is particularly important because of following situations or interaction between:
      the elderly patient, that has to be appreciated specific life values, dietary
      habits, culture and motoric, sensory and/or psychic handicaps and his, lay
      environment (acquaintances or relatives, inexpert in subsequent medical
      problems), or last his, medical environment and the positive or harmful
      interactions of the physicians and/or different therapeutic options.

PMID- 8296120
TI  - [The importance of therapy compliance in the treatment of arterial hypertension].
AB  - The hypertensive patient remains mostly asymptomatic and requires medication over
      his entire life. A sufficient follow-up may sometimes be difficult. Poor control
      of blood pressure is frequently due to inadequate compliance with the prescribed
      medication. This compliance is therefore a factor to be considered in any
      instance of a follow-up consultation of a hypertensive patient.

PMID- 8296121
TI  - [Compliance to therapy in daily practice].
AB  - Therapeutic possibilities have never been so numerous as nowadays. Although the
      physician may thus feel more powerful he is still deceived by the behaviour of
      his patients towards intake of the drugs he prescribes. If the risks of a poor
      compliance with pharmacotherapy are recognized adequate strategies can be
      developed in order to prevent this behavioural attitude which leads to
      therapeutic failure and waste financial resources. The follow-up of every
      pharmacotherapy should therefore be equally important as a just diagnosis.

PMID- 8296122
TI  - [Passive smoking and health].

PMID- 8296123
TI  - [Urine in the wrong place: urothorax].
AB  - Considering the only 38 cases which have been published one may believe that the
      accumulation of urine in the thorax would be a very uncommon cause of pleural
      effusion. But the lack of reported observations could also reflect a lack of
      suspicion. A leakage of the urinary tract following obstruction of various
      origins and/or a local trauma is known as urinoma. Due to excess pressure, this
      retroperitoneal or intraperitoneal collection of urine gives way to a
      transdiaphragmatic evasion. Therefore, a concomitant ipsilateral or bilateral
      pleural effusion should be suspicious of urinothorax. Thoracocentesis, followed
      by measurement of creatinine in the pleural fluid, is a simple procedure to
      establish the true diagnosis. This is a report of two patients with urinothorax,
      resulting from uterine and prostatic adenocarcinoma. In the first case, urine
      passed through a leakage of the bladder into the peritoneal cavity; in the second
      case, there was hydronephrosis with pelvic disruption.

PMID- 8296124
TI  - [Long-term course following kidney transplantation].
AB  - The first 100 recipients of cadaveric renal allotransplants operated at our
      institution between 1964 and 1971 were retrospectively analyzed in terms of a
      long-term follow-up, complications and survival parameters. Patient and graft
      survival (indicated in parenthesis) after transplantation were 68% (58%) at 1
      year, 50% (38%) at 5 years, 40% (27%) at 10 years, 32% (20%) at 15 years and 20%
      (13%) at 20 years. Half-life of graft survival was computed using two different
      mathematical models and was compared with the results of a control group operated
      in 1986. Half-life was 9.5 years for the study group and 13 years for the control
      group respectively.

PMID- 8296125
TI  - [Pigmentation disorders in systemic sclerodermia].
AB  - Skin pigmentation changes in systemic sclerosis have been known since the end of
      the last century. Many different aspects have been described. We report the case
      of a 48-year-old man with severe progressive systemic sclerosis who presented
      many different types of pigmentation changes of skin, but particularly a severe
      hyperpigmentation. This clinical observation suggests that local factors,
      including repetitive friction, trauma or variations in skin temperature, may
      influence the development, distribution and severity of pigmentation
      abnormalities in patients with systemic sclerosis. Physical treatments
      (connective tissue massage and lymphatic drainage) were very beneficial for our
      patient (healing of skin ulcerations and decrease of pigmentation.

PMID- 8296126
TI  - [Gonorrheal arthritis].
AB  - A 43-year-old female patient presented with migratory arthralgias, generalized
      exanthema and arthritis of the left elbow. She had a history of fever and chills
      three days earlier. Beside to a maculopapular and pustular rash and a joint
      involvement we found a swelling of the dorsal surface of her right hand without
      wrist effusion or synovitis. The clinical presentation was typical for the
      diagnosis of disseminated gonococcal infection (arthritis-dermatitis syndrome).
      Arthrocentesis was performed, and the cultures of the synovial fluid on chocolate
      agar were positive for Neisseria gonorrhoeae. The serologic examination for
      gonococcus was negative, it became positive some weeks later. The therapy with
      intravenous penicillin G 6 x 10(6) units/day for ten days was successful;
      unfortunately, we could not treat the partner. The present case report is
      illustrated with colour prints and describes the typical clinical picture of a
      diagnosis which is nowadays rare or even forgotten.

PMID- 8296127
TI  - [A case from practice (238). Benzodiazepine withdrawal delirium in a multidrug
      addict].

PMID- 8296128
TI  - [AIDS prevention: increased protection for women].

PMID- 8296129
TI  - [Thyroid diagnosis 1993].
AB  - Functional disorders of the thyroid and thyroidal tumors are a common challenge
      in daily practice. TSH of the 2nd and the 3rd generation stand in first place of
      the biochemical parameters in use. The FT4-test serves as confirming
      investigation. Additional investigations are reserved for special indications.
      Fine-needle aspiration performed by an experienced endocrinologist has the
      highest value to determine the benign character of a tumor of the thyroid.
      Anatomy can be optimally visualized by the modern ultrasound techniques. The most
      important indication for scintigraphy today is a scheduled therapy with
      radioactive iodine.

PMID- 8296130
TI  - [Thyroiditis].
AB  - The most common form of thyroiditis is undoubtedly chronic lymphocytic
      thyroiditis (Hashimoto's thyroiditis). It presents in the form of a small
      insignificant struma without any signs of inflammation, which is easily
      overlooked in our region (where once goiters due to iodine-deficiency have been
      common). Therapy is only indicated when the patient is disturbed by the size of
      the goiter or when he is hypothyroid. The disease can be easily diagnosed by
      palpation and investigation of autoantibodies. Repeated antibody-tests are not
      necessary, however, it is useful to measure TSH every two years since some of the
      patients develop hypothyroidism. In contrast to the relatively mild findings in
      Hashimoto's thyroiditis the subacute granulomatous thyroiditis (de Quervain)
      presents with an impressive clinical picture with pain, fever, malaise and
      elevated blood sedimentation rate, that may alarm the patient as well as the
      unexperienced physician. Treatment with prednisone is extremely effective and
      leads to complete remission.

PMID- 8296131
TI  - [Strategies in insulin treatment in insulin-dependent diabetes mellitus].
AB  - Late diabetic sequelae can be largely prevented by striving for near
      normoglycemic blood glucose control. In type-1 diabetes this can in most of the
      cases only be achieved by some sort of intensified insulin regimen. In this
      article the principle, advantages and drawbacks as well as the consequences for
      the patients' education are reviewed with respect to conventional, intensified
      'conventional' and functional insulin treatment.

PMID- 8296132
TI  - [Drug therapy of type-II diabetes: tablets, insulin or a combination of these].
AB  - Optimal therapy of diabetes has to be based on the known pathophysiology of
      metabolic disturbances and should eventually alleviate reduced secretion of
      insulin as well as reduce the usually present resistance to insulin in order to
      normalize the average blood glucose levels. In less than 30% of patients with
      type-II diabetes, dietetic measures combined with increased physical activity
      alone, are sufficient for metabolic control, thus increasing the importance of
      pharmacologic treatment immensely. Biguanides are the therapeutic choice in
      patients with massive overweight, because they usually do not induce weight gain;
      however, specific contraindications (renal failure in particular) have to be
      taken into consideration. The effect of blood glucose lowering by biguanides is
      not due to increased secretion of insulin, thus neither hypoglycemias nor
      hyperinsulinism are induced or increased, respectively. Patients with normal or
      slightly increased body weight should profit best from sulfonylureas that
      stimulate insulin production. Combinations of sulfonylurea and biguanides or of
      insulin and oral antidiabetics or insulin alone have to be taken into account
      when monotherapy with oral antidiabetics is too inefficient; however, clear and
      generally accepted guidelines for correct indications of these therapeutic
      modalities are lacking. Particularly in long-lasting diabetes and for patients
      with distinct overweight an adequate therapeutic success is often not obtained
      with the currently available therapeutic means. Possibly, future developments
      will provide new therapeutic ways with drugs that increase insulin sensitivity or
      reduce gluconeogenesis.

PMID- 8296133
TI  - [Can late sequelae of diabetes be avoided? Various critical observations].
AB  - Hyperglycemia plays a decisive role in development of diabetic retinopathy,
      nephropathy and neuropathy. Unfortunately, even modern antidiabetic means often
      fail to install normoglycemia or near normoglycemia. They also bear an important
      risk for hypoglycemia. What glucose levels (as measured by Hb-A1c) may be
      tolerated without consequences for the patient is unknown so far; therefore, we
      should presently still aim at lowering the blood glucose as often and as close to
      normal as possible and try to avoid severe hypoglycemias. Those who care for
      diabetics carry a high responsibility. The care diabetics should be improved as
      follows: Regular ophthalmologic controls could reduce occurrence of visual losses
      or blindness. Efficient lowering of hypertension prevents occurrence and
      progression of nephropathy. ACE-inhibitors turned out to be also useful in
      normotonic diabetics, because they prevent progression of nephropathy. Diabetics
      bearing a risk for lesions on the feet should be identified, instructed and
      treated adequately. This is the only way to reduce the rate of amputations. Risk
      factors for general arteriosclerosis should be efficiently treated or avoided,
      particularly in diabetics. In consideration of these factors, morbidity and
      mortality of diabetic patients could be influenced more efficiently. There is no
      justification for any defeatist attitude.

PMID- 8296134
TI  - [Hypercalcemia as incidental finding--what should be done?].
AB  - The discovery of a hypercalcemia validated by exclusion of hemoconcentration and
      follow-up calcium determinations opens the differential diagnosis of a malignancy
      and of hyperthyroidism whereas drug-induced causes can be recognized easily. A
      single determination of plasmatic parathyroid hormone (PTH) allows to safely
      distinguish between PTH-induced or PTH-independent, most often tumor-associated
      hypercalcemia. In both instances the patient may be free of symptoms particularly
      the very old one. Therapeutic measures are indicated in both instances: Treatment
      of malignancy-associated hypercalcemia is clinically effective and treatment of
      asymptomatic hyperthyroidism is likewise recommended, mainly to preserve bone
      mass and cerebral performance.

PMID- 8296135
TI  - [Problems with bone densitometry].
AB  - Today, bone density can be measured by different technical methods which show
      variations in terms of reproducibility, accuracy and sensibility. A crucial
      parameter is the reproducibility, which differs considerably from method to
      method. With densitometric methods it is possible not only to evaluate patients
      at risk getting an osteoporosis but also to establish an individual prophylaxis
      and therapy by means of highly precise quantitative methods, based on the
      parameters 'bone density' and 'loss of bone density'. A high bone turnover leads
      to fast bone loss and, vice versa, fast bone loss, measured by densitometry, is
      correlated with high bone turnover in postmenopausal women. This allows to
      establish an individual therapy with antiresorption resp. bone-stimulating agents
      and the knowledge about a tailored, individual treatment increases patients'
      compliance and reduces the rate of 'non-responders'.

PMID- 8296136
TI  - [Osteoporosis therapy, current status].
AB  - Treatment of osteoporosis includes various possibilities with drugs. Furthermore,
      approaches with physiotherapy and adequate diet are also important. As to drugs
      substances like calcium, estrogens, bisphosphonates, calcitonin, fluoride and
      vitamin D have to be mentioned. Anabolic steroids have some beneficial effects on
      bone, but there are problems with side effects. Strontium and ibriflavone show
      interesting potentials, but they need to be studied in more detail.

PMID- 8296137
TI  - [Magnetic resonance imaging in pneumology].

PMID- 8296138
TI  - [Occupational asthma: an experimental asthma. Apropos of isocyanate-induced
      asthma].
AB  - Isocyanate-induced occupational asthma is a model of experimental asthma related
      to the environment. Many of its features are identical with those of allergic
      asthma by sensitization to air-borne allergens. Exposure to isocyanate before the
      first symptoms of asthma varies from a few weeks to several years. The prevalence
      of isocyanate-induced asthma has been estimated at 5 to 25%. Atopy is found in
      less than 30% of the cases. A significant increase of HRBNS can be demonstrated
      in most patients, but it may be absent. It may also fluctuate with the working
      periods or after a bronchial provocation test with isocyanate. Elimination of
      this compound reduces the HRBNS level in only one quarter of the cases. Delayed
      or biphasic reactions are frequent: 30 to 60% depending of the authors. An early
      diagnosis followed by total elimination may result in complete cure, but more
      than 50% of the patients remain symptomatic and with HRBNS. An IgE-dependent
      mechanism can be demonstrated in about 20% of the cases. The course of isocyanate
      induced asthma is interesting in that the same phenomena are probably observed in
      chronic asthma resulting from repeated exposures to environmental allergens.

PMID- 8296139
TI  - [Acute drug-induced lung diseases with hypoxemia, cytotoxic drugs excluded].
AB  - Drug-induced acute lung diseases constitute a chapter of pneumology and intensive
      care that is now in full mutation. In practice, these diseases are still
      inadequately indexed and little known, the only exception being those caused by
      cytotoxic drugs observed in onco-haematology. They create for clinicians
      difficult diagnostic and therapeutic problems. From the cases reported in the
      literature, recent review papers and 10 personal cases, the authors ask five
      successive questions concerning hypoxic pneumopathies: 1) which patients?; 2)
      which clinical features?; 3) which initial diagnostic discussion?; 4) which are
      the elements likely to support the drug-induced hypothesis?; 5) which outcome?

PMID- 8296140
TI  - [Contribution of magnetic resonance imaging to the exploration of the
      mediastinum].
AB  - Magnetic resonance imaging (MRI) already has a number of indications in
      exploration of the mediastinum, the most frequent of which being exploration of
      vascular pathologies facilitated by visualization of vascular lumina without need
      for a contrast medium, MRI can provide detailed information concerning the size,
      relations and wall thickness of these vessels ans sometimes of aneurysmal
      thrombosis. It also makes it possible to study aortic dissections and venous
      diseases of the mediastinum. As regards mediastinal masses, MRI complements
      computerized tomography (CT): it is better than the latter to distinguish
      vascular relations and it provides aetiological arguments based on the intensity
      of T1 and T2-weighted signals.

PMID- 8296141
TI  - [Monotherapy using amoxicillin/clavulanic acid as treatment of first choice in
      community-acquired lung abscess. Apropos of 57 cases].
AB  - In a multicentre open prospective trial the effectiveness of AM-CA as first-line
      treatment of community-acquired lung abscess was evaluated in immunocompetent
      adult patients. AM-CA was administered intravenously in doses of 4 g/day for at
      least 7 days, then orally in doses of 2 g/day for at least 14 days. Radio
      clinical and laboratory evaluations were made during treatment, and 30 and 60
      days after it was discontinued. The results of this trial concerned 57 patients
      (48 men, 9 women; mean age 52 years). The facilitating factors were those usually
      found in lung abscess. Twenty-seven patients had previously received an
      antibiotic treatment which had failed. The clinical picture, built up gradually
      in 42/37 patients, consisted of infectious syndrome (52 cases), altered general
      condition (39 cases), purulent expectoration (47 cases), sometimes foetid (10
      cases), and thoracic clinical abnormalities (57 cases. X-ray films of the chest
      showed round abscess images (44 cases) or looked like necrotizing pneumonia (13
      cases) with pleural reaction (8 cases). Protecting bacteriological sampling by
      BFW brushing and transtracheal or transparietal sample collecting was performed
      in 41 of the 57 patients. The pathogens, isolated in 31 cases, were: S.
      pneumoniae 5; Streptococcus spp. 12; Staph. aureus 4; H. influenzae 7;
      Enterobacteriaceae 6; anaerobes 7. These organisms were associated in 8 cases.
      With the exception of Enterobacter cloacae, all were sensitive to AM-CA in-vitro.
      The outcome was satisfactory in 52 patients.

PMID- 8296142
TI  - [Radiological case. Diagnosis of polycyclic coin lesion of the left pulmonary
      hilum].

PMID- 8296143
TI  - [Endoscopic case. Endoscopic diagnosis of systematized opacity of the middle
      lobe].

PMID- 8296144
TI  - [Unusual complication of venous thrombosis of the upper limb: pulmonary
      hypertension].
AB  - Although less frequent than that of the lower limbs, venous thrombosis of the
      upper limbs may cause pulmonary embolism. This embolism is usually moderate and
      facilitated by the delay or absence of anticoagulant treatment. We report the
      case of a young man who had multiple and recurrent embolism consecutive to
      thrombosis of the axillary and subclavian veins and who rapidly developed
      pulmonary arterial hypertension on previously healthy lungs. There was no venous
      disease of the lower limb. After a more than 2 years' period, the pulmonary
      arterial hypertension is still moderate, but the patient remains under long-term
      antivitamin K therapy, this being the only available treatment capable of
      preventing a deterioration that would result in post-embolic cor pulmonale and
      ultimately require lung transplantation.

PMID- 8296145
TI  - [Acute respiratory insufficiency after pleural talcage of pneumothorax. Apropos
      of a case].
AB  - The authors report about one case of respiratory distress occurring after pleural
      talcage for pneumothorax. Although few cases have been published, this
      complication is known, and it should lead to carefully consider the indication of
      this technique and to limit the total amount of talc used.

PMID- 8296146
TI  - [Tracheobronchopathia osteochondroplastica. Personal observation and review of
      the literature].
AB  - Tracheobronchobathia osteoplastica (TBO) is a benign disease first described in
      1855 and rather rare since only 371 cases have been reported so far. The disease
      is characterized by the presence of subepithelial osteocartilaginous focal
      lesions without any relation to tracheal rings. The mechanism of its occurrence
      remains controverted. We report a case of TBO which is particular in that is was
      associated with atrophic rhinitis, polydactylia and disorder of oesophageal
      motricity. From a compilation of 113 cases published by French and Anglo-Saxon
      authors since 1970, it appears that the clinico-radiological and laboratory
      picture is of little help in the positive diagnosis which in fact rests on three
      key-points: bronchial endoscopy, pathological examination of bronchial biopsy
      fragments and thoracic imaging techniques including computerized topography and
      magnetic resonance imaging. The usually benign course of the disease can be
      marked by severe complications, such as infections, haemorrhages, acute dyspnoea
      by extension to the larynx or significant narrowing of the tracheal lumen which
      may need tracheotomy or surgical resection of the lesions.

PMID- 8296148
TI  - [Magnetic resonance imaging of the respiratory airways and the pulmonary
      parenchyma].
AB  - In the study of the proximal airways, MRI is mainly appropriate for the trachea
      and the mainstem bronchi, in case of tracheal stenosis or tumors. CT remains the
      reference examination for the distal airways. In alveolar condensation, MRI may
      help differentiating some of the involved materials (blood, lipids). Lastly, the
      role of MRI is limited in interstitial pathology, even though some indications
      may be appearing: fibrosis following radiation therapy, determination of the
      inflammatory component.

PMID- 8296147
TI  - [Pulmonary vascular disorders in hepatic diseases. From autopsy to mediators, 100
      years of history].

PMID- 8296149
TI  - [Ultrasonographic aspect of asbestos infracostal pleural plates].
AB  - The echographic study of the sub-costal pleura of 20 patients with occupational
      exposure to asbestos fibers and exhibiting pleural calcifications and thickenings
      on the chest X-Ray, allowed us to define the main semeiologic aspects of this
      pleural disease: horizontal striation and echo-poor thickenings of the sub
      pleural region and irregularities of the pulmonary surface generating Ring-Downs.
      Comparison of this group with 20 normal subjects quantified this pleural
      thickening (pleural plaques: 5.5 +/- 2.09 mm, limit values: 3 to 12 mm). Our
      results are similar to those of the recent literature on this subject. The
      interest of the echographic study of the pleura in patients submitted to asbestos
      fibers is enhanced by the easy use of the echographic procedure.

PMID- 8296150
TI  - [Bronchial cancer with normal thoracic image discovered by endoscopy. Apropos of
      11 cases].
AB  - The authors report about eleven cases, distributed over four years, of bronchial
      cancers with a normal thoracic image that were discovered on bronchial endoscopy.
      In this context, they sum up the limitations of medical imaging, the undisputed
      merits of bronchial endoscopy, and the major epidemiological and therapeutic
      features of this clinical form of bronchial cancer.

PMID- 8296151
TI  - [Severe hypoxemia in cirrhosis].
AB  - Various respiratory signs (other than infectious pathology), either very frequent
      and mild or very rare but with a poor prognosis, can be observed in cirrhotic
      subjects. Hypoxemia raises the greatest diagnostic problems in these subjects.
      The poor homogeneity of ventilation-perfusion ratios is the most commonly
      proposed cause of hypoxemia in cirrhosis. In such cases, hypoxemia is typically
      moderate (60-80 mmHg). Conversely, anatomical shunts, especially intrapulmonary
      ones, account for severe hypoxemia (< 60 mmHg). We are reporting about the case
      of a severe form of hypoxemia without anatomical shunt, caused by an anomalous
      ventilation-perfusion ratio in a female patient with ethylic cirrhosis.

PMID- 8296152
TI  - [Semi-invasive pulmonary aspergillosis. Apropos of a case].
AB  - A 43-year-old man was admitted to hospital for excavated pneumopathy of the upper
      part of the right lung, revealed by signs of respiratory infection evolving for a
      few weeks and involving a 10-kg weight loss. The radiological and clinical
      evolution and the demonstration of Aspergillus fumigatus allowed establishing a
      diagnosis of semi-invasive aspergillosis. The treatment, associating amphotericin
      B and 5-fluorocytosine, replaced by itraconazole 15 days later, soon produced
      clinical healing and radiological improvement. Since serology remained positive,
      surgery was performed to remove the residual lesions after a 7-month course of
      itraconazole. Within the scope of this case, the diagnostic criteria of this form
      of pulmonary aspergillosis are discussed, as well as the merits and limitations
      of itraconazole.

PMID- 8296153
TI  - [Pulmonary hypertension: a rare complication of hepatic cirrhosis].
AB  - Pulmonary hypertension is a rare pulmonary complication of chronic hepatic
      diseases. Anatomopathologic and clinic data are very similar to primary pulmonary
      hypertension. Although the lesions of arteriopathy are more related to portal
      hypertension than to hepatic lesions, the physiopathology of this morbid
      association is unknown.

PMID- 8296154
TI  - [Parotid metastasis disclosing bronchial carcinoma].

PMID- 8296155
TI  - [Central nervous system involvement and Wegener's disease].

PMID- 8296156
TI  - Signal transduction via MHC class-I molecules in T cells.

PMID- 8296157
TI  - Influence of tumour necrosis factor-alpha on the expression of Fc IgG and IgA
      receptors, and other markers by cultured human blood monocytes and U937 cells.
AB  - The expression of Fc receptors for IgG (Fc gamma R) and IgA (Fc alpha R) and of
      various other antigens on the human monocytic cell line U937 and peripheral blood
      monocytes, under stimulation with human recombinant tumour necrosis factor-alpha
      (TNF-alpha) and other cytokines, was investigated by flow cytometry. TNF-alpha,
      as well as interferon-gamma (IFN-gamma) or interleukin-6 (IL-6) had a significant
      up-regulating effect on U937 expression of Fc gamma RI/CD64. Furthermore, the
      action of TNF-alpha was augmented by IL-6, and more evidently by IFN-gamma. IFN
      alpha alone had only a marginal effect, but was able to increase the TNF-alpha
      driven Fc gamma RI expression. In contrast to U937 cells, TNF-alpha did not
      enhance significantly Fc gamma RI expression on human monocytes. Interestingly,
      on both U937 cells and monocytes, Fc alpha R was augmented markedly by TNF-alpha.
      Furthermore, TNF-alpha induced the expression of HLA-DR and HLA-DP antigens on
      monocytes and U937 cells. The expression of Fc gamma RII/CD32, FC gamma
      RIII/CD16, CD14, complement receptor type 1 (CR1/CD35), CR4 (CD11c/CD18), and MHC
      class-I antigens, was not influenced significantly by TNF-alpha. The results of
      this study show that TNF-alpha may act on human mononuclear phagocytes, alone or
      in combination with other cytokines, by modulating the expression of various cell
      surface antigens.

PMID- 8296158
TI  - Functional and biochemical properties of a mouse placental immunoregulatory
      factor.
AB  - The authors have a long standing interest in immune regulations which control the
      absence of rejection of a semi-allogeneic fetus by the mother. A previous work
      described a soluble 40 kDa factor extracted from mouse placenta and capable of
      inhibiting secondary immune responses in vitro. The present paper reports the
      following on its mode of action in vivo: (1) it is active even in a fully
      allogeneic host; (2) it can be administered i.v. or i.p. along with antigen; and
      (3) the injections of factor and antigen must not be more than 2 days apart for
      maximum efficacy. Moreover, the results of the study described here indicate also
      that this factor is a concanavalin A-binding glycoprotein, sensitive to heat and
      pronase, and different from interleukin 10 (IL-10). Thus, this placental factor
      appears to be different from previously described immune regulators such as IL-10
      and could contribute significantly to immune regulations at the level of the
      placenta.

PMID- 8296159
TI  - Clonotypic dominance and variable gene elements of pathogenic anti-DNA
      autoantibodies from a single patient with lupus.
AB  - This study explores the usage and diversity of the variable gene elements
      expressed by human lupus antibodies to DNA bearing the 0-81 idiotype, a marker of
      pathogenic anti-DNA autoantibodies. Rather than studying DNA-specific clonotypes
      from different patients, a panel of idiotype positive anti-DNA autoantibody
      secreting clones from a single individual were analysed. By cloning and
      nucleotide-sequencing the heavy-chain variable gene segments, evidence was found
      for dominance of clonotypic patterns. Also noted was a high rate of
      diversification among the variable (VH), diversity (DH) and junctional (JH) gene
      segments utilized, with a pattern of mutations indicative of antigenic selection.
      These features suggest that the clones secreting the lupus pathogenic
      autoantibodies have been selected over multiple generations through an affinity
      maturation process that is reminiscent of antigen-driven immune responses.

PMID- 8296160
TI  - IgM and IgG subclass distribution of human anti-Ro/SSA 60 kDa autoantibodies.
AB  - The Ro/SSA and La/SSB antigens are common targets for autoantibodies found in the
      sera of patients with Sjogren's syndrome and SLE. The anti-Ro/SSA and anti-La/SSB
      antibodies often appear together but are not cross-reactive. This paper describes
      the humoral autoimmune response to the Ro/SSA 60 kDa protein moiety with respect
      to the presence of IgM and IgG1-4 antibodies. IgM antibodies to the Ro 60 kDa
      protein coexisted with IgG anti-Ro 60 kDa antibodies in nearly half of the sera.
      A similar fraction also contained IgM anti-La/SSB antibodies. The frequency of
      sera with IgM antibodies of both specificities was that expected from random
      overlap. A predominating IgG1 anti-Ro 60 kDa response was found in all patients,
      but anti-Ro 60 kDa antibodies of the other IgG subclasses were present also in a
      high number of sera. This is in contrast to the reported IgG subclass
      distribution of anti-La/SSB antibodies. Mapping of IgM and IgG1-4 antibody
      recognition of different parts of the Ro 60 kDa protein was also performed. IgM
      and IgG1-4 antibodies of all sera reacted with the central part of the Ro 60 kDa
      protein, encompassing amino acid residues 181-320.

PMID- 8296161
TI  - VH-gene family dominance in ageing mice.
AB  - The cellular composition and VH-gene family repertoire were compared in different
      B-cell compartments from young adult (8-12 weeks) and old (18-24 months) C57BL/6
      and BALB/c mice. Ageing mice were found to have a higher frequency of peripheral
      mature B cells utilizing genes from a single VH-gene family. While in each
      individual old C57BL/6 mice cells expressing the VH J558 gene family consistently
      were over-represented, a marked individual variation was observed in old BALB/c
      mice with increased frequency of either the VH J558, Q52 or J606 families. Aged
      mice were found also to have a reduced number of bone-marrow pre-B cells and an
      augmented number of splenic Ig-secreting cells. These results suggest that old
      mice express less diversified antibody repertoires possibly as a consequence of
      reduced input from precursors and increased peripheral selection, which may be
      responsible for the progressive establishment of immunodeficiency.

PMID- 8296162
TI  - Increased expression of VLA-5 adhesion molecules on synovial fluid T lymphocytes
      in chronic polyarthritis: a consequence of T-cell activation.
AB  - This study focuses on the consequences of T-lymphocyte activation in chronic
      polyarthritis in terms of expression of cell surface receptors interacting with
      extracellular matrix (ECM). The expression of the VLA group of integrins was
      studied on in vitro-stimulated peripheral-blood T cells, and on peripheral-blood
      and synovial-fluid mononuclear cells (MNC) of patients with polyarthritis. The
      VLA expression was measured by flow cytometry using monoclonal antibodies (MoAbs)
      against alpha-subunits of the VLA family. VLA-alpha 4 and VLA-alpha 5, but not
      VLA-alpha 1, were expressed on a major fraction of unstimulated peripheral-blood
      T cells both in the patients with polyarthritis and in healthy individuals. Two
      distinct populations, VLA-alpha 5-high and VLA-alpha 5-low, were found in resting
      peripheral-blood T lymphocytes. Two days after stimulation by phorbol 12
      myristate 13-acetate (PMA) and concanavalin A, most T cells became VLA-alpha 5
      high. In patients with chronic polyarthritis, the expression of VLA-alpha 1 and
      VLA-alpha 5 was always higher on synovial-fluid T cells than on peripheral-blood
      T cells. These results give further support to the hypothesis that upon
      activation the induction of the VLA adhesion-molecule expression may be a factor
      contributing to the accumulation of T cells in the inflamed synovium.

PMID- 8296163
TI  - Lectin receptors on IgA isotypes.
AB  - It has been shown previously that secretory IgA interacts with the mannose
      specific lectin of Escherichia coli. The purpose of the study described here was
      to evaluate whether the N-linked oligosaccharide chains of the human IgA isotypes
      IgA1 and IgA2 differ in lectin receptor activity. A range of plant lectins
      specific for N-linked oligosaccharide chains were tested for their ability to
      precipitate IgA1 and IgA2 myeloma proteins, secretory IgA and free secretory
      component. IgA2 myeloma proteins reacted more strongly than IgA1 with the mannose
      specific lectin ConA, whereas IgA1 myeloma proteins reacted more strongly than
      IgA2 with two galactose-specific lectins, Ricinus communis agglutinin I and Abrus
      precatorius agglutinin. This suggests that IgA2 possesses a larger proportion of
      short truncated complex type oligosaccharide chains and/or oligomannose type
      chains than IgA1. Further, IgA2 reacted more strongly than IgA1 myeloma proteins
      with Lens culinaris (lentil) lectin, and Pisum sativum (pea) lectin, suggesting
      that IgA2 exposes more of short, complex type chains fucosylated on the core than
      IgA1. The differences demonstrated in receptor activity between IgA1 and IgA2 may
      be important in their interaction with the microbial flora, as well with
      endogenous lectins, such as phagocyte receptors.

PMID- 8296164
TI  - Purification and characterization of mannan-binding protein from mouse serum.
AB  - Mouse mannan-binding protein (MBP) was identified in serum by its Ca(2+)
      dependent binding to mannan. On gel permeation chromatography, the protein eluted
      corresponding to a molecular weight of approximately 750 kDa. Analysed on SDS
      PAGE under reducing conditions, the polypeptide showed an apparent molecular
      weight of 28 kDa, while several high molecular weight bands were seen under non
      reducing conditions. The presence of collagen-like domains within the molecule
      was indicated by a high glycine content (14.9%) and substantiated by sensitivity
      to collagenase. Rabbit anti-mouse MBP antisera were raised. The concentration of
      MBP in serum from normal mice was measured by rocket immunoelectrophoresis and
      found to be from below 1 microgram/ml to 100 micrograms/ml (average 50
      micrograms/ml, n = 60). The binding of mouse MBP to mannan could be inhibited by
      mono- and disaccharides in the following order of potency: L-fucose > D-mannose >
      N-acetyl-D-glucosamine > maltose > D-mannoheptulose > D-glucose > N-acetyl-D
      mannosamine >> lactose > D-galactose >> N-acetyl-D-galactosamine. Mouse MBP was
      shown to activate the classical complement cascade after binding to mannan. The
      sequence of 14 NH2-terminal amino acid residues of the molecule showed 93%
      identity to rat MBP-A and complete identity to the translated cDNA sequences for
      mouse MBP-A and mouse Ra-reactive factor component P28b (RaRF P28b) published
      previously. The amino acid composition of mouse MBP showed a high degree of
      homology to MBPs from other species and mouse RaRF P28b.

PMID- 8296165
TI  - Differential effects of IL-10 on proliferation and cytokine production of human
      gamma/delta and alpha/beta T cells.
AB  - Gamma/delta TCR bearing T lymphocytes represent a T-cell subset whose functional
      relevance remains unclear. Nevertheless these T cells may play a role in the
      early immune response against bacteria. Until now the regulatory mechanisms on
      this response have not been investigated. The study described here evaluated the
      immunoregulatory effects of Interleukin-10 on gamma/delta and alpha/beta TCR
      positive T-cell clones and freshly isolated peripheral-blood mononuclear cells
      (PBMC). IL-10 has been shown previously to inhibit lectin and antigen-induced
      proliferation and cytokine production by alpha/beta T cells. The results outlined
      below show that rhIL-10 strongly inhibits lectin-induced production of IFN-gamma,
      TNF-alpha, IL-2, and to a lesser degree proliferation and IL-4 production of both
      T-cell subsets. As IL-10 did not inhibit proliferation but at the same time
      strongly suppressed cytokine production in various experiments, the hypothesis
      that it could function as a growth factor for human T cells as has been described
      for murine thymocytes was tested. The data demonstrate that, although the
      gamma/delta T-cell clones tested do not produce IL-10 they can use it as a growth
      factor in combination with IL-2, IL-4 or alone. Furthermore, IL-10 has the same
      properties on human alpha/beta T-cell clones and PBMC. In summary, it is shown
      that IL-10 has pleiotropic effects on gamma/delta and alpha/beta TCR+ T cells by
      inhibiting lectin-induced cytokine production and by acting as a growth factor
      for these cells alone or in combination with IL-2 or IL-4.

PMID- 8296166
TI  - Hamster hepatic amyloid A (AA) protein is derived from a novel member of the SAA
      gene family.
AB  - The nearly complete amino acid sequence of casein-induced hepatic hamster AA is
      described. Hamster AA appeared to be C-terminally ragged as found in other
      species. Furthermore, the N-terminus was (partially) truncated. Hamster hepatic
      AA sequence showed high homology with, but was not identical to hamster SAA
      isotype sequences deduced earlier from mRNA in hepatic and extra-hepatic tissue.
      Therefore, hamster hepatic AA is derived from a novel member of the SAA gene
      family. However, the origin of hepatic AA-amyloid remains unclear.

PMID- 8296167
TI  - [Ground water hygiene at the Institute of Water, Soil, and Air Hygiene].

PMID- 8296168
TI  - [Plant pesticide pollutants in ground water. Detection, evaluation, prevention].

PMID- 8296169
TI  - [Possibilities for decontamination of pesticide-contaminated drinking water
      supply area].

PMID- 8296170
TI  - [Modification of ground water quality by airborne pollutants].

PMID- 8296171
TI  - [Considerations for development of modern ground water protection].

PMID- 8296172
TI  - [Point and surface contamination by PCDD/PCDF in the soil of an industrial area
      exemplified by Hamburg].

PMID- 8296173
TI  - [Use and exposure oriented evaluation of ground water contaminating old
      pollutants and disposal sites--new knowledge and methods].

PMID- 8296174
TI  - [Microbiological degradation of mixed hydrocarbons in soil samples from a used
      oil contaminated site].

PMID- 8296175
TI  - [Risk assessment of old hazardous substances. Treatment needs from the viewpoint
      of environmental health experts].

PMID- 8296176
TI  - [Inorganic and organic substances in rain water runoff and disposition in
      underground water passage].

PMID- 8296177
TI  - [Modification of ground water quality by unsealed water channels].

PMID- 8296178
TI  - Psychosocial factors at work and musculoskeletal disease.
AB  - The objective of this review is to establish whether the epidemiologic literature
      presents evidence of an association between psychosocial work factors and
      musculoskeletal disease. In a hypothetical model it is suggested that individual
      characteristics and stress symptoms can modify this relationship. The reviewed
      studies do not present conclusive evidence due to high correlations between
      psychosocial factors and physical load and to difficulties in measuring dependent
      and independent variables. Nevertheless, it is concluded that monotonous work,
      high perceived work load, and time pressure are related to musculoskeletal
      symptoms. The data also suggest that low control on the job and lack of social
      support by colleagues are positively associated with musculoskeletal disease.
      Perceived stress may be an intermediary in this process. In addition, stress
      symptoms are often associated with musculoskeletal disease, and some studies
      indicate that stress symptoms contribute to the development of this disease.

PMID- 8296179
TI  - Influence of job strain and emotion on blood pressure in female hospital
      personnel during workhours.
AB  - A homogeneous sample of 56 women who were between the ages of 20 and 59 years and
      worked in acute emergency care, child psychiatry, or a pediatric outpatient
      clinic comprised the subjects of this study to determine the relationship between
      job strain and blood pressure. Job strain was measured with a standardized
      questionnaire, and blood pressure during workhours with self-triggered equipment.
      Endocrine factors (morning concentration of plasma prolactin, cortisol, and
      dehydroepiandrosterone) and emotional states recorded in diaries were also
      studied. Significant interrelationships occurred among perceived job strain,
      plasma prolactin, and diastolic blood pressure during workhours even when body
      mass index, age, family history of hypertension, level of education, and mood
      state were adjusted for in a multiple regression analysis. Thus job strain of
      female care givers was associated with systolic and diastolic blood pressure
      during workhours and also with diastolic blood pressure at rest, but not with
      blood pressure during leisure time.

PMID- 8296180
TI  - Impact of regular relaxation training on the cardiac autonomic nervous system of
      hospital cleaners and bank employees.
AB  - The work-related strain of 50 female hospital cleaners and 48 female bank
      employees was recorded during a period of rationalization in the workplace, and
      the effect of daily relaxation to help the workers cope was tested. The subjects
      were arranged into age-matched pairs and randomly allocated into intervention and
      reference groups. The intervention period lasted six months. The relaxation
      method was brief and easily introduced as an alternative break in the workplace.
      Each training session lasted 15 min. A microcomputer-based system was used to
      record heart rate variability in response to quiet breathing, the Valsalva
      maneuver, deep breathing, and active orthostatic tests. Cardiac reflexes
      indicated that occupational strain (especially of a mental nature) caused the
      functioning of the autonomic nervous system to deteriorate. Regular deep
      relaxation normalized the function and improved the ability to cope.

PMID- 8296181
TI  - Risk indicators of ischemic heart disease among male professional drivers in
      Sweden.
AB  - Possible risk indicators of ischemic heart disease relevant to the occupation of
      professional driving were identified in a cohort of 440 professional drivers and
      1000 referents from the Swedish countries of Vasterbotten and Norrbotten. The
      subjects were randomly selected. Data on cardiovascular risk indicators were
      collected from questionnaires, blood pressure measurements, serum lipid levels,
      height, and weight. The results showed that significantly more drivers than
      referents were overweight, smokers, and shift workers; were sedentary in their
      leisure time; and had a work situation characterized by high demands, low
      decision latitude, and low social support. There were no significant differences
      concerning blood pressure and serum lipid levels. The odds ratio for having a
      high score on a cardiovascular risk index was 3.18 (95% confidence interval 2.41
      4.20) for the drivers when they were compared with the referents. When adjusted
      for age, heredity, shift work, educational level, marital status, and working
      class, the odds ratio was 2.34 (95% confidence interval 1.70-3.21).

PMID- 8296182
TI  - Urinary mercury excretion in chloralkali workers after the cessation of exposure.
AB  - Seventeen former chloralkali workers were followed through the regular
      determination of urinary mercury for nearly two years after the cessation of
      exposure to mercury vapor in a study of the time course of urinary mercury
      elimination. Their duration of exposure ranged from 3 d to 35.5 years. A one
      compartment model for urinary mercury elimination was applied. The urinary
      mercury concentration declined at a rate indicating a half-time of 91 d. When
      corrected for an individual base-line level of urinary mercury resulting from
      sources of mercury intake not related to work, the half-time was 72.4 [95%
      confidence interval (95% CI) 63.2-81.7] d, with a mean elimination rate constant
      of 0.011 (95% CI 0.008-0.013).d-1. The day-to-day variability of the urinary
      mercury concentration averaged 22%, expressed as the coefficient of variation
      between urine samples delivered on three consecutive days.

PMID- 8296183
TI  - Bronchial responsiveness and the reproducibility of forced expiratory volume in
      one second.
AB  - Although poorly reproducible spirometric tests, "test failures," are associated
      with respiratory morbidity, it is not clear what causes them. Bronchial
      responsiveness was examined in relation to test failure for forced expiratory
      volume in 1 s (FEV1.0) (1979 definition of the American Thoracic Society) in 249
      bakers, 165 chemical industry workers, and 204 office workers. The first two
      groups were studied by the same methods and were combined. Test failure was
      observed in 4%, and for 38% the provocative dose of inhaled methacholine causing
      a 20% fall in FEV1.0 relative to FEV1.0 after the inhalation of normal saline
      (PD20) was < or = 120 mumol (7% with a PD20 of < or = 8 mumol). Test failure was
      not related to the level of PD20. Of the office workers, 3% had test failure, 11%
      a PD20 of < or = 8 mumol of histamine, and no significant relation was observed.
      The study does not exclude the possibility that bronchial responsiveness might be
      related to test failure in patients with airway disease or that a clearer
      relation might be demonstrable in a larger study, but it does suggest that it is
      not a major determinant of test failure.

PMID- 8296184
TI  - Association between asbestos-related pleural plaques and resting
      hyperventilation.
AB  - This study reports an association between pleural plaques and resting
      hyperventilation in a group of workers exposed to asbestos. Information on
      exposure level, pack-years of cigarette smoking, chest radiographs, ventilation
      parameters, single-breath diffusing lung capacity, and arterial gases were
      obtained for 344 workers. After the exclusion of 37 workers for isolated
      parenchymal fibrosis, combined pleuroparenchymal fibrosis, or diffuse pleural
      thickening, 55 subjects with isolated pleural plaques were evaluated against 252
      no-plaque workers. A quantitative pleural score revealed mild pleural disease.
      Forty-four workers with plaques (80%) had hypocapnia induced by resting
      hyperventilation. The quantitative pleural score correlated significantly with
      the partial pressure of carbon dioxide in arterial blood (correlation coefficient
      = 0.7). A decrement in forced vital capacity was associated with plaques, whether
      controlled for age, smoking, and exposure or not. It was concluded that the
      resting hyperventilation observed in some asbestos-exposed subjects is related to
      the presence of mild pleural plaques and a restrictive disorder.

PMID- 8296185
TI  - Organizational factors influencing serious occupational accidents.
AB  - The aim of this article is to examine organizational factors influencing serious
      occupational accidents. The study was part of a larger project investigating 99
      serious occupational accidents in southern Finland. A workplace analysis and an
      accident analysis were done at accident sites. In connection with this
      investigation, 73 victims, 91 foremen, and 83 co-workers were interviewed with a
      structured questionnaire. The results showed that the need to save time, tight
      schedules, and a lack of caution had a greater influence on accidents than did
      the foremen, co-workers, customers, professional pride, curiosity, or the wage
      system. Big companies had the lowest risk of serious occupational accidents.
      Accident risk was significantly greater for subcontractors than for main
      contractors.

PMID- 8296186
TI  - Injury to the cornea due to fish bile.
AB  - A retrospective study of 207 patients with chemical eye injuries in northern
      Norway revealed that fish bile was the causal agent in 14%. Fish bile caused
      superficial corneal erosions in 28 of 29 cases. All but one of the patients were
      professional fishermen or fish industry workers. In one case delayed medical care
      led to serious corneal opacity. Provided that there was immediate and abundant
      rinsing of the affected eye and good medical care, the prognosis of fish bile
      injuries was fairly good. The mechanisms for corneal damage due to fish bile are
      not clear.

PMID- 8296187
TI  - Meeting of the IARC working group on beryllium, cadmium, mercury and exposures in
      the glass manufacturing industry.

PMID- 8296188
TI  - [Clinical importance of karyotype in hematology].
AB  - Cytogenic analysis of leukemic cells has proven to be a mandatory part of the
      diagnosis of malignant hemopathies. Recurring clonal cytogenetic abnormalities
      may be divided into those exclusively associated with myeloid disorders, those
      uniquely observed in lymphoid diseases, and those detected in both myeloid and
      lymphoid hemopathies. Several of the common defects are characteristic of
      specific FAB types or subtypes and are associated with specific clinico
      pathologic syndromes and clinical complications. Cytogenetic abnormalities have
      served to define relatively homogeneous subsets of malignant hemopathies which
      are not evident from morphological and other available markers. Cytogenetic
      findings have been demonstrated to be powerful indicators in predicting clinical
      course and outcome in patients and in guiding their management. Given the
      significant progress made in the treatment of malignant hemopathies, it is very
      important to identify parameters which may be used to predict whether patients
      will respond favorably to standard therapies or if they are unlikely to do so and
      require alternative strategies, such as bone marrow transplantation. Cytogenetic
      studies have also provided important insights into the understanding of malignant
      transformation processes. In a number of recurring chromosome translocations
      characteristic of leukemias and lymphomas the genes that are located at the
      breakpoints have been identified. Molecular analysis has revealed that alteration
      in expression of these genes or in the properties of the encoded proteins
      resulting from the rearrangements plays an integral part in malignant
      transformation. Studies of clonality have suggested that several chromosome
      abnormalities may arise in pluripotent hemopoietic stem cells, whereas others may
      originate in cells of more restricted lineage. The author focuses first on the
      implications of the karyotype in the diagnosis and the prognosis of
      myeloproliferative syndromes, acute leukemias and myelodysplastic syndromes, then
      on the interest of describing new clinical-cytogenetic associations. Finally,
      some of the recent results obtained in a cytogenetic study of myelodysplastic
      syndromes are discussed.

PMID- 8296189
TI  - [Chronic myeloid leukemia. State of the art, May 1993].
AB  - New developments in relation to chronic myelogenous leukemia (CML) are
      characterized by progress in knowledge of pathogenesis, diagnostic improvement
      such as nosology of Philadelphia-negative CML and diagnosis of minimal residual
      disease by molecular techniques, advances in drug therapy with hydroxyurea or
      interferon alpha, and progress in bone marrow transplantation through
      availability of unrelated donors. In addition, the recognition of suitable
      prognostic parameters indicates that risk adapted therapy may become possible.

PMID- 8296190
TI  - [How long should cyclosporin be administered following bone marrow
      transplantation?].
AB  - After organ transplantation, life-long immunosuppression is mandatory to prevent
      rejection. This is not the case after allogeneic bone marrow transplantation
      (BMT). The mechanisms of tolerance are little understood and there is little data
      about the required duration of immunosuppression. In a retrospective study we
      analyzed the use of cyclosporine A (CyA) treatment in all BMT patients who where
      transplanted in Basel from 1979 to 1991. 243 patients with a median age of 26 (2
      49) years received CyA to prevent graft-versus-host-disease (GvHD) and rejection.
      206 patients had leukemia, 26 severe aplastic anemia and 10 a lymphoproliferative
      disorder. All were treated according to a common CyA regimen with initial
      parenteral administration followed by oral treatment for a year; after 1988
      treatment duration was reduced to 6 months. Drug dosage was adjusted according to
      clinical symptoms, plasma levels and toxicity. At relapse of the original disease
      CyA was always withdrawn. Three months after BMT 96% were still on CyA. After 6
      months 79%, after 1 year 61%, after 2 years 29%, after 3 years 18%, after 4 years
      15%, after 5 years 8% and after 8 years 2% of patients were still taking CyA. All
      20 patients who are still alive 10 years after BMT are off CyA. CyA was
      administered parenterally for a median of 31 (5-147) days. Oral treatment started
      at day 25 (4-28). The oral dose was reduced 5 (1-20) times, increased once (1-75)
      and finally discontinued after a median time lapse of 1 year (14d-8y).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8296191
TI  - [Old and current aspects of intravenous immunoglobulin therapy].
AB  - The natural variety of IgG isotype function suggests the use of IgG for
      therapeutic purposes. Whereas the clinical efficacy of substituting IgG through
      the i.m. and i.v. routes in combating infectious complications has long been
      known, the usefulness of i.v. IgG in comparatively high doses for the treatment
      of autoimmune disease states has been discovered serendipitously upon observing
      normalized platelet concentrates in IVIG-treated patients with immune
      thrombocytopenias. In such situations, a network of regulated humoral immune
      capacity, inherent to the large plasma pool of healthy donations, is conferred on
      the recipient and helps to reestablish homeostasis of deficient immune function.
      The indications for IVIG in diseases with abnormal immunity are rarely first
      choice but must be considered when conventional and cheaper options have failed.
      This is the case with the following diseases: idiopathic thrombocytopenic
      purpura, myasthenia gravis, Guillain-Barre disease, systemic lupus, rheumatoid
      arthritis, Evans syndrome, auto- and alloimmune cytopenias,
      polymyositis/dermatomyositis as well a haemorrhagic syndrome due to inhibitors
      against clotting factor VIII. In order to achieve synergism, a combination of
      IVIG with other therapeutic measures such as immunosuppressive agents, plasma
      exchange and/or immunosorption may be advisable. With such combinations,
      particularities in disease dynamics may be taken into account acceptable dosage
      recommendations for the treatment of autoimmune disease are not always available.
      The mechanisms of action of successful IVIG infusions are not yet completely
      understood. Those experimentally identified include: neutralization of autoimmune
      induction mechanisms; activity as anti-idiotypic agents; down-regulation of the
      Fc receptor apparatus, up-regulation of interleukin-1 receptor antagonist;
      deviation of complement activation to non-inflammatory targets and modulation of
      superantigens.

PMID- 8296192
TI  - [Prognostic value of bone marrow examinations on day 8 and day 17 of the first
      induction therapy cycle in acute myeloid leukemia].
AB  - Bone marrow examination yields valuable diagnostic information for evaluation of
      treatment efficacy in acute myelogenous leukemia (AML) patients. However, the
      ideal timing of this procedure remains to be defined. Usually the first follow-up
      examination is performed on day 17 of the induction course. Since an earlier
      analysis might be helpful in deciding on the subsequent treatment strategy, we
      explored whether an examination on day 8 might be equivalent, in particular in
      terms of quality of the specimen, as compared with that on day 17. In 10 AML
      patients undergoing the same induction treatment, bone marrow aspirates were
      examined prospectively at diagnosis (day 0), immediately after termination (day
      8) and on day 17 of the first treatment course. We found that the number of cells
      not classifiable due to artifacts, as well as the otherwise non-evaluable cells,
      did not differ significantly in aspirates obtained on day 8 as compared with
      those on day 17. The number of leukemic cells decreased significantly from day 0
      to day 8, whereas no change was noted between days 8 and 17. We conclude that a
      marrow examination on day 8 is not more prone to misinterpretation due to
      artifacts than our standard examination on day 17. Thus, an early marrow analysis
      immediately after completion of the first induction cycle might be a helpful tool
      in evaluating course of AML.

PMID- 8296193
TI  - [Treatment of severe idiopathic cold-agglutinin diseases using interferon-alpha
      2b].
AB  - Cold agglutinin disease is an immunohemolytic anemia in which the autoantibody
      directly agglutinates human red blood cells below body temperature, maximally at
      0 to 5 degrees C. The disease is considered to occur in primary (idiopathic) or
      secondary forms. The secondary form is noticed in the setting of infections (e.g.
      Mycoplasma pneumoniae, infectious mononucleosis), or patients with
      lymphoproliferative disorders. Affected patients show varying clinical
      presentation ranging from mild to serious hemolytic anemia, episodic
      hemoglobinuria, acrocyanosis, or other peripheral vaso-occlusive events which are
      all occasioned by cold exposure. In mild chronic cold agglutinin disease
      preventing cold exposure usually suffices to avoid disease exacerbation. However,
      treatment of severe disease is difficult. Splenectomy or glucocorticoids are
      generally disappointing, but exceptions have been reported. Treatment with
      alkylating agents, as for example chlorambucil or cyclophosphamide, may be
      effective in some patients. However, late effects, and in particular their
      carcinogenic potential when used as long-term treatment, must be born in mind. We
      report on a 59-year-old woman with severe cold agglutinin disease who was at
      first treated successfully with chlorambucil and prednisone. Based on in vitro
      evidence, primary cold agglutinin disease can be considered as a low grade
      malignant lymphoproliferative disorder in which interferon-alpha has been shown
      to be an effective therapeutic agent, at least in forms such as hairy cell
      leukemia. We therefore switched therapy to interferon-alpha 2b (three million
      units/m2 body surface area subcutaneously three times weekly). 18 months after
      treatment initiation there was no remission, but improvement of clinical and
      laboratory signs of the disease was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296194
TI  - [Isolation ward: initial experiences after 4 years].
AB  - Since October 1988 there has been an isolation ward at Basle Cantonal Hospital.
      Its purpose is to treat patients with high dose chemotherapy and bone marrow
      transplantation under protective isolation and by standardized criteria. The
      isolation ward has two sub-units, viz. the reverse isolation for neutropenic
      patients (8 single room units) and the LAF unit (5 laminar airflow units) for
      allogeneic bone marrow transplantation (BMT). Up to July 1992, 287 patients (152
      males and 133 females) required 527 hospitalizations. The median age was 41 (5
      82) years in the reverse isolation unit and 28 (4-61) years in the LAF unit. Bed
      occupation was 90% and 82% throughout the period. 71% of patients were from the
      Basle area and the rest from elsewhere in Switzerland or from other countries.
      DIAGNOSIS: acute leukemias (112); myelodysplastic or myeloproliferative syndromes
      (52); severe aplastic anemia or agranulocytosis (46); lymphoproliferative
      syndromes (50); solid tumors (28). Indications for hospitalisation: BMT (107);
      complications after BMT (infections, GvHD) (63); chemotherapy on protocols of
      SAKK (105); other chemotherapies (64); antilymphocyte globulin or growth factor
      treatment (27); splenectomies (18); neutropenic fever (62); patient work-up (59);
      terminal care (20). Patients in reverse isolation were hospitalized for a median
      17 (1-142) days; in the LAF unit for 52 (1-121) days.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8296195
TI  - Anatomy and histophysiology of lymphoid tissue.

PMID- 8296196
TI  - Clinical approach to lymphadenopathy.

PMID- 8296197
TI  - Immunophenotypic and immunogenotypic approaches useful in distinguishing benign
      and malignant lymphoid proliferations.
AB  - Distinguishing benign and malignant lymphoproliferative disorders by purely
      morphologic criteria can be difficult. Immunophenotypic analysis is a useful
      adjunct to the morphologic evaluation of lymphoproliferative disorders and is of
      considerable assistance in resolving difficult diagnostic dilemmas.
      Immunophenotypic analysis can be performed on virtually any pathologic specimen
      using a variety of methodologic approaches. The analysis should be tailored to
      the individual pathologic specimen and the specific diagnostic problem. The
      results should be correlated with the clinical and morphologic findings. Southern
      blot hybridization analysis of the antigen receptor genes has proven to be an
      objective, accurate, and sensitive method by which to determine the lineage and
      clonality of lymphoid proliferations and to detect clonal B- and T-cell
      populations that are not recognizable morphologically or immunophenotypically.
      Polymerase chain reaction-based strategies extraordinarily more sensitive than
      Southern blotting are currently being developed. However, the demonstration of
      clonal antigen receptor gene rearrangements is an indication of clonality and not
      necessarily of malignancy, although the two are closely related. This and all the
      other biologic and technical limitations of immunogenotypic analysis must be
      considered when evaluating the results of such studies. Ideally, the results of
      immunogenotypic analysis should be interpreted only in conjunction with the
      results of morphologic evaluation and immunophenotypic analysis.

PMID- 8296198
TI  - Autoimmune and iatrogenic causes of lymphadenopathy.

PMID- 8296199
TI  - Angioimmunoblastic lymphadenopathy with dysproteinemia.

PMID- 8296200
TI  - Multicentric Castleman's disease.

PMID- 8296201
TI  - Uncommon syndromes of reactive lymphadenopathy.

PMID- 8296202
TI  - The Epstein-Barr virus and the distinction between benign and malignant
      lymphoproliferative processes.

PMID- 8296203
TI  - Hormone replacement therapy: benefits and risks for the general postmenopausal
      female population and for women with a history of previously treated breast
      cancer.

PMID- 8296204
TI  - [Study on the mechanisms of thrombin to inhibit neurite outgrowth].
AB  - In the present study, we investigated the effects and signal transduction
      mechanisms of thrombin on neuronal differentiation of human primitive
      neuroectodermal tumor cell line CHP-100. Thrombin inhibited neurite outgrowth of
      CHP-100 cells in culture induced by serum removal. The inhibitory effects were
      found to be associated with activation of phosphatidylinositol turnover/calcium
      mobilization signal transduction pathway by thrombin, since stimulation with
      thrombin induced significant inositol-1, 4, 5 trisphosphate accumulation and
      intracellular free calcium transient in CHP-100 cells. In addition, the most
      potent inhibitor of thrombin hirudin, which reversed the inhibitory effect of
      thrombin on neurite outgrowth of CHP-100 cells, also inhibited thrombin
      stimulated calcium transient. These results suggest a specific role of thrombin
      signal transduction pathway in the regulation of neuronal differentiation.

PMID- 8296205
TI  - [Effects of ethanol and norepinephrine injected into nucleus hypoglossus on the
      genioglossal muscle activities].
AB  - Integrated genioglossal and phrenic muscle activities were recorded on 87
      urethane anesthetized, vagotomized rabbits to study the effect of ethanol and
      norepinephrine (NA) injected into nucleus hypoglossus on the potentiating effects
      of integrated genioglossal and phrenic muscle activities (PIMA). It was found
      that ethanol could inhibit PIMA of genioglossal muscle. Peak amplitude of PIMA
      (PAMP) was reduced with the latency of PIMA (LAT) prolonged and recovery time
      (RT) shortened. Norepinephrine facilitated PIMA, which could be blocked by
      Tolazolin. Local administration of ethanol (2 mol/L 1 microliter) to the caudal
      part of the 4th ventricle floor produced statistically significant reduction in
      genioglossal muscle activities (P < 0.01) in resting respiration. The present
      results suggest that ethanol exerts inhibitory effect on genioglossal muscle
      activity which may be associated with the inhibition of nucleus hypoglossus per
      se or caudal part of the 4th ventricle floor. The excitatory activity of
      genioglossal muscle may be mediated by noradrenergic receptors in the nucleus
      hypoglossus.

PMID- 8296206
TI  - [Protective effect of nerve growth factor on cholinergic neurons corpus striatum
      of new born rat subjected to hypoxia-ischemia].
AB  - Cerebral hypoxia-ischemia was produced in 7 day old rats by right common carotid
      artery occlusion combined with systemic hypoxia. In the hypoxic-ischemic group
      animals, striatal ACh contents on both sides were reduced to a significant extent
      in commensurate to AChE histochemical image analysis. All these changes could be
      restored to normal control by a protection dose (50 micrograms) of NGF
      intraventricularly injected.

PMID- 8296207
TI  - [An analysis of the central pathway of vestibulo-sympathetic responses].
AB  - In order to elucidate the relationship between several structures of CNS and the
      vestibulo-sympathetic response (VSR) in rat, the technique of spike triggering
      average (STA) was used. The spike of the neuron which responded to the pendular
      rotation (pendular positive unit, PPU) was used to trigger the onset of averaged
      activities of the splanchnic nerve (SN). Making use of the spike of PPU of
      nucleus vestibularis medialis (NVM) as an indicator, the SN-STA had a latency of
      33.28 +/- 3.1 ms. SN-STA triggered by PPU of reticular formation (RF) of caudal
      brain stem, a positive response with a latency of 11.13 +/- 0.91 ms was observed.
      SN-STA triggered by PPU of vestibulocerebellum, a positive response with a
      latency of 21.86 +/- 1.73 ms was observed. Our results suggest that the nearest
      supraspinal relay may be the nuclei of medical RF in caudal brain stem and the
      descending flow of VSR was probably transmitted by the slow conducted fibers of
      reticulo-spinal tract. According to the latency of SN-STA by PPU of vestibulo
      cerebellum, the vestibulcerebellum possibly executed a polysynaptic mission
      between the transmission of VSR outflow from NVM to RF nuclei of caudal brain
      stem.

PMID- 8296208
TI  - [Effects of stimulating lateral hypothalamic area and ventromedial nucleus of
      hypothalamus on cerebellar cortical neuronal activity in the cat].
AB  - In pentobarbital anaesthetized cat, stimulating lateral hypothalamic area (LHA)
      and ventromedial nucleus (VMN) of the hypothalamus could elicit inhibitory,
      excitatory or inhibitory-excitatory responses of cerebellar Purkinje cells (PC)
      and non-Purkinje cells (NPC) in the loubles VI and VII. The majority of responses
      are inhibitory (80.4%) usually with a latency of 10-20 ms, or occassionaly as
      long as 90 ms. Usually stimulation of LHA was more effective and NPC was more
      responsive. The aforementioned inhibitory response could be blocked by iv.
      chlorpheniramine. The possible role of the hypothalamo-cerebellar activity was
      discussed.

PMID- 8296209
TI  - [Effect of electrical stimulation of second somatosensory cortex on the response
      of primary somatosensory cortex to C-fiber inputs].
AB  - When the projecting point of saphenous nerve in second somatosensory cortex (S
      II) of cat was stimulated, the evoked potentials elicited by C-fiber inputs of
      saphenous nerve recorded in the primary somatosensory cortex (C-CEP) might be
      either inhibited or facilited according to whether the superficial and/or the
      deeper layer of the cortex was stimulated. The inhibition was expressed as a
      decrease of amplitude and prolongation of latency of C-CEP; while the
      facilitation, as an increase of amplitude and duration of C-CEP. When the
      superfaicial layer of S II was stimulated by weaker current, both inhibitory and
      facilitatory effects could be observed, but only inhibitory effect was observed,
      when the deep layer was stimulated. With the same intensity of stimulation,
      inhibitory effect was more pronounced when the deep layer rather than the
      superficial layer was stimulated. It is suggested that S II may play a role in
      the modulation of C-CEP of S I.

PMID- 8296210
TI  - [Change of beta tubulin gene expression in the motoneurons of spinal cord during
      nerve regeneration].
AB  - After crushing the right sciatic nerve of rat, the contents of both tubulin and
      beta tubulin mRNA increased significantly in the ventral horns of spinal cord.
      Analysis of tubulin in bilateral ventral horns by SDS-PAGE showed that tubulin in
      the injured side increased by 17%-121% of the control side. The results of in
      situ hybridization indicated with the signals of hybridization with beta tubulin
      cDNA probes were 27%-70% higher in motoneurons of the ventral horns in the injury
      side than the control. Northern blotting analysis of tubulin mRNA in ventral
      horns also revealed an increase of tubulin gene expression.

PMID- 8296211
TI  - [Effects of pressor area of ventral surface of medulla oblongata on the
      vasotonicity of renal vessels of rats].
AB  - Electrical stimulation of the pressor area of the ventral surface of medulla
      oblongata (VSMp) of rat elicited an enhancement of renal sympathetic nerve
      activities (RSNA) and an increase of MAP, pressure of kidney (PPK), which
      depended on the integrity of renal sympathetic nerve (RSN). The effect of VSMp on
      PPK could be blocked by alpha 2-adrenoceptor antagonist yohimbine, but not by
      alpha 1-adrenoceptor antagonist prazosine when VSMp was stimulated. alpha 2
      adrenoceptor agonist clonidine perfused renal vessels induced PPK increase
      similar to that due to stimulation of VSMp. The results indicate that the effect
      of VSMp on PPK are mediated by RSN of alpha 2 type sympathetic transmitter in the
      tonic control renal vascularture.

PMID- 8296212
TI  - [The effect of trilostane and dexamethasone on serum amino acids and TNF in
      endotoxemic rats].
AB  - By the use of specific endogenous GC biosynthesis inhibitor Trilostane and
      exogenous GC Dexamethasone (Dex), we established three rat models with similar
      severity of endotoxemia, but different plasma GC level. With these models we
      studied the effect of elevated plasma GC on serum TNF, pathological changes of
      vital organs and the changes in serum amino acids and glucose concentration in
      comparable endotoxemic condition. It was observed that plasma GC level was
      negatively correlated with the maximum TNF concentration, but positively
      correlated with the liver tyrosine transaminase activity, serum amino acids and
      glucose concentrations and as the serum GC level was elevated, the pathological
      changes of intestine, stomach, liver and lungs became less pronounced. From these
      results, it was supposed that in severe endotoxemia hypersecration of endogenous
      GC and maintenance of high level plasma GC are essential for animals to alleviate
      tissue injuries by reducing the overproduction of the host-derived mediators such
      as TNF and promoting the metabolism of amino acids and glucose.

PMID- 8296213
TI  - [Role of nucleus accumbens in cardiovascular activities and its relationship with
      opioid peptides in rats].
AB  - In this study, electrical stimulation and microinjection in nucleus accumbens in
      urethane-anesthetized rats were conducted to observe the effect of electrical
      stimulation of nucleus accumbens on blood pressure and heart rate. The following
      results were observed: (1) Electrical stimulation of the nucleus accumbens of rat
      resulted in significant hypotension and bradycardia. (2) Kainic acid
      microinjected into the nucleus accumbens, could abolish the effects mentioned
      above. (3) Naloxone administered to the nucleus accumbens could block the
      cardiovascular inhibitory effect evoked by electrical stimulation of nucleus
      accumbens. The intra-accumbens injection of mu-receptor agonist, DAGO could also
      elicit hypotension and bradycardia to an extent comparable to that of the effect
      due to electrical stimulation, whereas kappa-receptor agonist, U-50 had no such
      an effect. (4) When the cardiovascular inhibitory effect elicited by electrical
      stimulation of the nucleus accumbens was observed, the discharge activity in
      locus ceruleus was also decreased. (5) Bilateral vagotomy could abolish the
      change in heart rate elicited by the electrical stimulation of nucleus accumbens,
      but not the hypotension. It is suggested that the mu-opioid receptors of neurons
      in nucleus accumbens are involved in cardiovascular activity.

PMID- 8296214
TI  - [Effect of hypoxia on the conversion of angiotensin I to A II in pulmonary
      vascular endothelial cells].
AB  - The effect of hypoxia on intrapulmonary conversion of angiotensin I (A I) to
      angiotensin II (A II) was examined by using an isolated rat lung preparation
      perfused at constant flow and cultured calf pulmonary artery endothelial cells.
      The conversion rate of A I in endothelial cells of pulmonary vascular bed was
      found to be decreased in both acute hypoxic and chronic hypoxic (CH-5000, CH
      8000) rats. The conversion rate of A I to A II was significantly higher in acute
      hypoxic rat lungs than that in denuded endothelial cells rat lungs. There was no
      significant difference between chronic hypoxic and denuded endothelial cells rat
      lungs. In cultured calf pulmonary artery endothelial cells (PAEC) exposed to
      hypoxia (3% O2) for 30 minutes the conversion of A I to A II was significantly
      reduced. In the time course of hypoxic exposure the conversion of A I to A II in
      cultured calf PAEC showed significant difference between hypoxia and normoxia.
      The results indicated that (1) Acute and chronic hypoxia impaired pulmonary
      conversion of A I to A II. (2) Effect of hypoxia on the pulmonary conversion of A
      I to A II is associated with the degree and the time of hypoxia.

PMID- 8296215
TI  - [Effect of human hepatic stimulator substance on intracellular calcium and
      potassium homeostasis in CCl4-intoxication dissociated hepatocytes].
AB  - The human hepatic stimulator substance (hHSS) was extracted from abortive fetal
      liver according to the method of LaBrecque. The intracellular free calciumion was
      measured by fluorescent probes Fura-2/AM. Rat hepatocytes were isolated from
      liver by the method of Seglen and intoxicated by CCl4 vapour, then the changes of
      [Ca2+]i, the leakage of intracellular K+, ALT and viability of hepatocytes were
      observed. The results were as follows: The hHSS does exist in the human fetal
      liver, hHSS could increase the viability of intoxicated hepatocytes, maintain the
      intracellular calcium homeostasis, and decrease the leakage of intracellular
      potassium and ALT into the culture medium. These results indicate that hHSS could
      protect hepatocytes against CCl4 through maintaining calcium homeostasis,
      preventing potassium leakage and sustaining stability of hepatocyte polasmalemma.

PMID- 8296216
TI  - [Electroacupuncture enhances enkephalin mRNA expression in the spinal cord and
      medulla, an in situ hybridization study].
AB  - Previous studies in this laboratory have shown that electroacupuncture (EA)
      accelerated the release of enkephalin in the spinal cord. The present study was
      undertaken to investigate the effect of EA stimulation on the expression of
      preproenkephalin (PPE) mRNA in the rat spinal cord and medulla by in situ
      hybridization histochemical technique. Animals were administrated with 2 Hz EA
      stimulation (1-2-3 mA, 30 min) applied at acupoints sanyingjiao and zusanli of
      one hind leg. The rats were perfused 24 h after EA, and quantitative changes of
      PPE-mRNA expression were determined by emulsion autoradiography. EA stimulation
      was found to increase the number of neurons expressing PPE-mRNA in spinal cord
      and medulla. Increased expression of PPE-mRNA was more marked in ipsilateral
      dorsal horn of spinal cord (especially in laminae III-IV and contralateral
      ventromedial medulla (especially in the lateral paragigantocellular reticular
      nucleus). The results provide evidence in support of the enkephalinergic
      hypothesis of acupuncture analgesia. It is suggested that increased biosynthesis
      of enkephalin precursor would help to compensate for the loss of tissue storage
      of enkephalin during the period of EA stimulation.

PMID- 8296217
TI  - [Platelet neuropeptide Y and its vasoconstriction effect in rat].
AB  - Specific radioimmunoassay showed that in rat neuropeptide Y (NPY) immuno
      reactivities (IR) in platelets and platelet rich plasma (PRP) were respectively
      90 +/- 16 ng/10(7) platelets and 93 +/- 19 ng/ml. Both values were much greater
      than those in the plasma (1.2 +/- 0.1 ng/ml, P < 0.001) and platelet poor plasma
      (PPP) (1.7 +/- 0.3 ng/ml, P < 0.001). The NPY-IR in rat platelets eluted at the
      same position as authentic NPY on reverse phase HPLC. The NPY-IR in the platelets
      prepared from the PRP aggregated maximally by collagen reduced to 34 +/- 5
      ng/10(7) platelets, while the NPY-IR in the PPP prepared from the same PRP
      increased to 26 +/- 4 ng/ml. PPP 1.6 ml prepared from the aggregated PRP induced
      contraction of isolated rat caudal arteries with the maximal tension of 380 +/-
      80 mg; while the maximal contraction induced by 1.6 ml of the same PPP pretreated
      with NPY anti-serum was only 190 +/- 40 mg (P < 0.001). Authentic NPY 1 nmol/L
      did not cause any contraction. The results indicate that rat platelets contain a
      high concentration of NPY, which can be released during irreversible platelet
      aggregation. The NPY released can potentiate vasoconstriction responses induced
      by co-released substances during platelet aggregation.

PMID- 8296218
TI  - [Effects of angiotensin II, atrial natriuretic peptide III and arginine
      vasopressin on activity of paraventricular neurons of rat hypothalamic slices].
AB  - The effects of angiotensin II (AG II), atrial natriuretic peptide III (ANP III)
      and arginine vasopressin on 101 paraventricular nucleus (PVN) neurons from 28
      brain slices of rats were observed. After perfusing the brain slices with AG II
      (10(-7) mol/L, 3 min), spontaneous discharge rate of 28/50 (56.0%) neurons was
      significantly increased, while that of 5/50 (10.0%) was significantly decreased
      and 17/50 (34.0%) neurons were non-responsive. Both of excitatory and inhibitory
      effects of AG II on neurons in PVN were completely blocked by AG II receptor
      blocker saralasin (10(-6) mol/L). As the brain slices were perfused with ANP III
      (10(-7) mol/L, 3 min), the firing rate of 16/26 (61.54%) neurons was decreased,
      while that of 1/26 (3.85%) neurons was increased and 9/26 (34.61%) neurons were
      non-responsive. During perfusing brain slices with AVP (10(-7) mol/L, 3 min), the
      firing rate of 19/25 (76.0%) neurons was significantly increased, while that of
      1/25 (4.0%) neurons was decreased and 5/25 (20.0%) neurons were non-responsive.
      Twenty-five PVN neurons were successively perfused with three peptides. Among
      them, 4 were excited by both AG II and AVP, 2 were excited by AG II and inhibited
      by ANP III, and 7 were excited by AVP and inhibited by ANP III. The results show
      that the discharge rate of PVN neurons may be affected by AG II, ANP III and AVP.
      It is likely that PVN acts as an integrative site for neuroendocrine and
      autonomic functions.

PMID- 8296219
TI  - Factors in perceived hospital discharge planning effectiveness.
AB  - Hospital discharge planning is the process of assessing the needs of hospitalized
      patients for post-acute care and developing a coordinated plan to provide the
      care needed. It is an important component of both the financial viability of the
      hospital and of the overall quality of care provided to the patient across health
      care settings, and has historically been an important part of social work
      practice. This research, based on a random sample survey of U.S. non-federal
      acute medical/surgical hospitals (N = 378 hospitals), suggests those variables
      that may be most important in shaping the effectiveness of the hospital discharge
      planning program. A multivariate analysis framework is used to identify those
      variables that have the strongest independent effect on effectiveness, and to
      assess the relative strength of each. Power (including discharge planner
      influence and physician and hospital administrator support) and role clarity
      emerge as the most important predictors of perceived effectiveness. The model of
      discharge planning used and characteristics of the hospital (such as size or
      urban-rural location) are not significant independent predictors. The single most
      important factor is cooperation and support from the physician staff of the
      hospital. This research suggests that organizational factors, rather than the use
      of a particular "system" of discharge planning, may be most important in
      discharge planning effectiveness.

PMID- 8296220
TI  - Psychosocial implications of service dog ownership for people who have mobility
      or hearing impairments.
AB  - Service dogs for people with mobility impairments and hearing ear dogs for
      persons with hearing impairments have grown in popularity because the important
      practical tasks these dogs perform enhance the independence of their owners.
      Little is known about the psychosocial impact of service dog ownership, however.
      The results of a survey of 24 owners and seven trainers on the psychosocial
      benefits and liabilities of service dog ownership are presented and the
      implications for social work practice are discussed.

PMID- 8296221
TI  - Bioethics: social work's response and training needs.
AB  - Hospital social workers (N = 255) from ten urban teaching hospitals in seven
      states were surveyed regarding their practice responses and training needs in
      bioethics. Responses to twenty-one practice situations in bioethics were analyzed
      in terms of levels of encountering ethical concerns, clinical participation and
      preparedness to handle ethical concerns. Whereas worker responses were greater in
      practice situations appearing more psychosocial than biomedical in nature,
      training needs were greater in those situations appearing more biomedical than
      psychosocial in nature. Rationing of health care, the number one training need
      across service specialties, stands out as the practice situation in which ethical
      concerns were encountered with the least preparation and participation. Prior
      training in ethical principles and analysis and service on a hospital ethics
      committee associated significantly with higher levels of worker responses.
      Implications for social work education and practice in today's health care
      environment are presented.

PMID- 8296222
TI  - An assessment of gender as a factor among severely mentally disabled case
      management clients.
AB  - Ninety-four clients who were receiving intensive case management services were
      assessed for gender differences on a variety of sociodemographic and clinical
      characteristics, functioning level, social network and subjective and objective
      quality of life. The high degree of similarities among male and female clients in
      the study suggests the possibility that mental disability is more socially
      handicapping than gender. An alternative explanation is that there is a paucity
      of gender sensitive measures available to evaluate mental health services.
      Regardless of gender, younger clients were less satisfied with their living
      arrangement and were less satisfied with family relations, although young women
      were least satisfied with family relations. The need for development of gender
      sensitive measures and the development and evaluation of services addressing
      needs of women with serious mental illness is discussed.

PMID- 8296223
TI  - Journey of separation: elderly Russian immigrants and their adult children in the
      health care setting.
AB  - The adult children of elderly Russian immigrants often react to their parents'
      medical illness and subsequent hospitalization with maladaptive behaviors. This
      paper posits that the underlying issue behind such behaviors is the emotional
      separation between the elderly immigrants and their adult children, an issue
      which becomes especially prominent during the parent's health crisis. It examines
      the psycho-cultural factors of the clients' past as well as the migration-related
      losses that impinge upon their ability to work through this separation. The paper
      introduces a model of social work intervention aimed at helping the immigrants to
      negotiate separation in the context of the health care setting. It provides a
      case example and recommendations for social work treatment.

PMID- 8296224
TI  - Survival bonding: a response to stress and work with AIDS.
AB  - There is ample literature describing the ongoing stressors and tremendous
      emotional impact on health care professionals caring for patients with AIDS. This
      paper is a report of a research study which explored collegial relationships and
      staff retention to determine factors that reduced staff burnout. The study
      explored an observed phenomenon of pairing among staff members of various
      disciplines, working with patients with AIDS, in a tertiary care hospital. The
      authors called this phenomenon "survival bonding." These informal but intense
      relationships offered staff a mutually supportive environment which reduced their
      anxiety, stress, and helped prevent burnout. Given the growing volume of HIV
      infected persons, and the increased work load of many health care professionals
      in the aids field, it is important to understand the complex emotional and social
      support needs of staff to prevent burnout and to improve staff recruitment and
      retention.

PMID- 8296225
TI  - [Amylin and amyloidosis of the pancreatic islets and their significance in the
      etiology and pathogenesis of diabetes mellitus type 2].

PMID- 8296226
TI  - [The immune status in different clinical forms of insulin-dependent diabetes
      mellitus].
AB  - Immune status with reference to the disease duration and genetic factors (HLA
      typing) was studied in various clinical variants of insulin-dependent diabetes
      mellitus. The disease duration appeared the key factor in development of immune
      deficiency in insulin-dependent diabetes mellitus. Critical immunological values
      were established (CD5+ cells--1200 in 1 microliter, CD4+ cells--35%, expression
      of CD5 and antigens HLA class II--110 and 75%, respectively) for septic
      complications which are highly probable in lower indices. Females with diffuse
      thyroid enlargement, subclinical hypothyroidism, wide spectrum of antibodies to
      DNA, antigenic determinants of thyroid gland, hypophysis were found to be a group
      associated with HLA--DR3 carriage.

PMID- 8296227
TI  - [Lipid peroxidation and the antioxidant protection of the erythrocytes in
      diabetes mellitus patients].
AB  - The study included 16 patients with diabetes mellitus (DM) type 1 and 15 healthy
      controls. By the moment of examination the patients had achieved subcompensation.
      10 patients developed diabetic vascular complications. The patients received
      biosynthetic insulins Humulin S, Humulin I, Humulin M3. Pretreatment glycemia in
      the patients surpassed that in the controls, MDA red cell levels per ml of
      hemolysate were higher by 121% and 130% per protein 1 mg. MDA measured equal both
      in angiopathy patients and those without it. The activity of the antioxidant
      enzymes in DM patients was similar to control indices. Human insulin
      administration reduced red cell MDA levels both in angiopathy and free of it
      patients, though in the former MDA remained higher than normal, while in the
      latter normal levels are obtained. The parameters of the antioxidant defense
      enzymes changed on the treatment week 12: catalase activity rose by 41%, that of
      superoxide dismutase and glutathione peroxidase lowered by 35 and 65%,
      respectively. Variations in these enzymes activity showed no dependence on
      vascular complications.

PMID- 8296228
TI  - [Diabetes mellitus in patients with chronic alcoholic pancreatitis].
AB  - The examination of 170 patients with chronic alcohol pancreatitis revealed
      diabetes mellitus (DM) in 21% of them. It manifested with polydipsia, polyuria
      and weight loss along with pancreatitis symptoms. DM complications were rare.
      Exercise tests were indicative of reduced insulin and glycagon reserves in the
      majority of the examinees. This condition depended on pancreatitis severity. DM
      in pancreatitis presents a high risk of hypoglycemia which should be taken into
      consideration when designing schemes of relevant treatment.

PMID- 8296229
TI  - [The use of highly purified Iletin-II-type porcine insulins and human insulin
      preparations in clinical practice].
AB  - The paper presents the results of treatment with insulins of iletin-II and
      humulin series. Decreased insulin doses, absence of complications, stable
      compensation of diabetes mellitus, reduction of insulin antibodies titer suggest
      high clinical effectiveness of the above preparations. Because of low
      immunogenicity humulin insulins are preferable when compared to iletin-II ones.

PMID- 8296230
TI  - [The treatment of acute suppurative pyelonephritis in diabetes mellitus
      patients].
AB  - The analysis of clinical, diagnostic and treatment efficacy data has been made
      for 160 diabetes mellitus patients (50 cases of insulin-dependent and 110 of
      noninsulin-dependent) with acute purulent pyelonephritis (APP). A diffuse form of
      the disease was detected in 100 patients (62.5%), purulent-destructive one in 60
      patients (37.5%). Intoxication, resistant to insulin decompensation of diabetes
      mellitus, sepsis may be resultant from latent APP. Nondestructive forms of APP
      were responsive to antibacterial and detoxication therapy combined with
      catheterization of the urinary tracts. On demand, conservative therapy was
      reinforced with renal drainage by nephrostomy. Primary nephrectomy was
      recommended in purulent-destructive forms and purulent para-nephritis. Radical
      surgery in intensive and advanced purulent-destructive pyelonephritis produced a
      decrease in postoperative lethality by 26.8%. Adequate therapeutic policy
      provided positive results in 80% of the patients. Lethal outcomes (20%) were due
      to grave diabetes mellitus and APP.

PMID- 8296231
TI  - [The use of immunoregulator preparations in the combined treatment of idiopathic
      hypothyroidism].
AB  - A comparative analysis of idiopathic hypothyroidism (IHT) outcomes in different
      therapeutic regimens which incorporated or did not incorporate splenin and sodium
      nucleinate showed more frequent disease exacerbations in patients who received no
      immunoactive drugs. Combined therapy reduced the number of patients with
      decompensation 3.7-fold. Stable IHT compensation was achieved in those patients
      who had received adjuvant splenin in 80.8% of cases, sodium nucleinate in 86.2%
      against a 40.9% response rate under conventional replacement therapy with
      thyreoidin.

PMID- 8296232
TI  - [Diabetes mellitus: is it possible to curb its prevalence and the incidence of
      late vascular complications?].

PMID- 8296233
TI  - [The effect of heredity and environmental conditions on the development of
      atherogenic metabolic shifts].
AB  - Lipid metabolism and lipid peroxidation (LPO) were studied in residents of St.
      Petersburg (healthy subjects without atherosclerosis history, healthy relatives
      of atherosclerotic patients, postmyocardial infarction patients, post-apoplectic
      patients and coronary heart disease sufferers) versus matched subjects living in
      rural area. Altogether 215 patients were examined. Besides genotype factors,
      lipid metabolism and LPO were found responsive to environmental factors. These
      were especially potent in changing the activity of superoxide dismutase,
      glutathione peroxidase, catalase. In those living in the country myeloperoxidase,
      superoxide dismutase and catalase activity was higher than in city population.
      The latter exhibited, though, higher activity of glutathione peroxidase. It is
      evident that more advantageous ecological conditions have distinct
      antiatherogenic action on lipid metabolism and LPO, especially, suggesting
      possible treatment of atherosclerosis by moving to more healthy locality as
      regards environmental pollution.

PMID- 8296234
TI  - [The clinico-pathogenetic aspects of sex dimorphism in gout].
AB  - The examination of 241 gout patients (207 males and 34 females) revealed a marked
      sexual dimorphism of the disease related to the articular and renal syndromes.
      Male gout is characterized by higher blood levels of uric acid and oxypurinole in
      reduced clearance of the latter, while in female gout there were
      hyperxanthinoxidasemia and hypo-cAMPemia. Unbalance of sex and gonadotropic
      hormones, which appeared multidirectional and dependent on the sex, was observed
      in males in the form of lower concentrations of blood testosterone and estradiol
      against elevated levels of progesterone and lutropin, in females manifested with
      hypoprogesteronemia and reduced gonadotropin.

PMID- 8296235
TI  - [Acute pneumonia in patients with multiple primary malignant neoplasms].
AB  - The authors review 35 cases of acute pneumonia (AP) in 30 patients with
      multifocal cancer. As a rule, AP was focal, ran a moderate or severe course,
      arose acutely with high temperature, chill, cough, purulent discharge.
      Auscultation registered weak vesicular breath, moist rale. Among pathological
      agents prevailed associations of pneumococci with gram-negative flora. AP
      resolved for 3-4 weeks in 2/3 of the patients, the rest of them developed
      lingering disease. From the point of view of antibacterial drugs efficacy, wide
      spectrum drugs are preferable.

PMID- 8296236
TI  - [The use of clindamycin and netilmicin for preventing postoperative wound
      infection in patients with cancer of the upper respiratory and digestive tracts].
AB  - Clindamycin (2.7 g/day) and netilmicin (5.6 mg/kg) were used for 6-10 days in 27
      patients with laryngeal and oral cancer versus beta-lactam antibiotics and
      aminoglycosides received by 56 matched patients to prevent infection of the
      operative wound. Suppuration was observed in 11.1 and 41.4% of the patients,
      respectively (p < 0.05), the temperature rose over 38 degrees C in 22.2% and
      42.9% of the patients, respectively (p < 0.05). The regimens showed similar
      toxicity. The findings proved high efficacy of clindamycin combination with
      netilmicin in infection prophylaxis in patients operated on for upper respiratory
      and digestive tract cancer.

PMID- 8296237
TI  - [Experience in using the new antiemetic preparation Navoban in hemoblastosis
      patients].

PMID- 8296238
TI  - [The treatment of chronic myeloleukemia with recombinant alfa-2 interferon].
AB  - A trial has been conducted of recombinant alpha 2-interferon (reaferon) used in
      32 patients with Ph'[correction of Rh']-positive chronic myeloid leukemia (CML).
      A chronic stage was in 3, transient in 3 and blast in 1 patients. 25 CML patients
      were newly diagnosed. The treatment lasted from 2 months to 3 years.
      Clinicohematological remission was confirmed conventionally and by the degree of
      Ph'-positive clone reduction. An attempt is made to clarify the mechanism
      underlying the resistance to reaferon basing on the immunological data (detection
      of antireaferon neutralizing antibodies). The authors propose a combined
      treatment (myelosan plus reaferon) of CML which has obvious advantages over
      myelosan monotherapy.

PMID- 8296239
TI  - [Psoriasis: the treatment and prevention of recurrences].

PMID- 8296240
TI  - [Lamisil in the therapy of foot mycoses].
AB  - A new antimycotic drug lamisil (Sandoz, Switzerland) was given as pills to 35
      patients with pedal mycosis (23 of them suffered from onychomycosis). Pedal
      mycosis was cured for 2 weeks, onychomycosis for 12 weeks. In 2 cases the drug
      was discontinued because of gastrointestinal toxicity. By tolerance and efficacy,
      lamisil is superior to griseofulvin and nizoral.

PMID- 8296241
TI  - [Sibicort in the treatment of dermatoses].

PMID- 8296242
TI  - [The use of fraxiparin for the prevention and treatment of thromboembolism in
      patients with heparin-induced thrombocytopenia].
AB  - Seventeen patients aged 26-52 with recurrent thromboembolism of the veins and
      disturbances of cerebral and coronary circulation (3 and 2 cases, respectively)
      treated by unfractionated heparin developed thrombocytopenia in the presence of
      enhanced platelet aggregation. Despite heparin therapy, fresh thrombi of
      different sites appeared in 5 patients. A cross to fraxiparin (France) resulted
      in correction of thrombocytopenia, normalization of spontaneous platelet
      aggregation in two thirds of the patients. In 5 patients thrombocytopenia
      persisted. It is stated that in most cases low-molecular heparin allows
      continuation of antithrombotic therapy in heparin-induced thrombocytopenia.
      Neither transplacental passage nor hemostatic abnormalities in the newborns were
      recorded after administration of fraxiparin to 6 pregnant women.

PMID- 8296243
TI  - [The use of fraxiparin in orthopedic trauma patients to prevent and treat
      pulmonary embolism and deep venous thrombosis of the extremities].

PMID- 8296244
TI  - [The use of plasmapheresis in treating urology patients].
AB  - The paper presents the results of plasmapheresis inclusion into a combined
      therapy of pyelonephritis. Out of 79 patients treated, 42 had urosepsis, 25
      developed pyelonephritis in pregnancy, 12 had complicating chronic renal failure.
      Uroseptic patients were examined for hemostasis, the rest for immune status.
      There were symptoms of DIC syndrome in the former and immunity suppression in the
      latter. After the combined therapy with plasmapheresis, latent hypercoagulation
      and intoxication disappeared, uroseptic manifestations reduced. The above
      treatment of pregnancy pyelonephritis stopped inflammation, promoted activation
      of the immune system. In patients with chronic renal failure adjuvant
      plasmapheresis enhanced cellular and humoral immunity, neutrophil function, the
      number of middle-size molecules in the blood diminished. The latter improved
      renal function in decreasing uremia.

PMID- 8296245
TI  - [The potentials and outlook for using computer systems in medical education].

PMID- 8296246
TI  - [The genetic aspects of the development of diabetic nephropathy (a review of the
      literature)].

PMID- 8296247
TI  - [The methodological aspects of the testing control of student knowledge].

PMID- 8296248
TI  - Use of near fatal asthma for investigating asthma deaths.

PMID- 8296249
TI  - Airway hyperresponsiveness: relation to asthma and inflammation?

PMID- 8296250
TI  - Development of bronchus associated lymphoid tissue (BALT) in human lung disease:
      a normal host defence mechanism awaiting therapeutic exploitation?

PMID- 8296251
TI  - Near fatal asthma attacks: the reliability of descriptive information collected
      from close acquaintances.
AB  - BACKGROUND: The reliability of information collected from close acquaintances of
      the deceased in studies on mortality from asthma has not been assessed. As part
      of a South Australian asthma mortality study, levels of agreement for information
      obtained directly from cases--that is, cases who had experienced near fatal
      asthma attacks--were compared with corresponding information concerning these
      cases obtained independently from close acquaintances. METHODS: The first 51
      subjects presenting from the outset of the main study to hospital accident and
      emergency departments with near fatal asthma attacks were included to gain an
      early assessment of the reliability of responses. The level of agreement between
      self reported information and that obtained from close acquaintances was compared
      by means of a kappa statistic or intraclass correlation coefficient, depending on
      the measurement scale. Both score one for complete agreement and zero when there
      is no agreement. RESULTS: High levels of agreement were found for questions
      relating to use of hospital services, with agreement levels ranging from 0.92 for
      visits in the past month to accident and emergency departments, to 0.86 for prior
      hospital admissions and 0.78 for prior need for assisted ventilation. Levels of
      agreement for drug treatment ranged from 1.00 for use of beta agonists to 0.64
      for corticosteroid use, and to a low 0.24 for use of sodium cromoglycate. There
      was moderate agreement for histories of regular use of over the counter
      medications without a medical consultation (0.57). Psychiatric characteristics
      showed moderate levels of agreement, with values of 0.44 for personal history of
      psychiatric consultations and 0.50 for denial score. Agreement scores were 0.66
      for doctor visits in the past month, 0.66 for limitations in daily activities,
      0.76 for loss of work days in the past month, 0.59 for severity of asthma, and
      0.55 for frequency of asthma attacks in the past month. Poorer agreement scores
      were found for trends in asthma symptoms (0.21) and frequency of symptoms during
      the past three years (0.12). Sleep disturbance was also associated with a low
      agreement score (0.25). CONCLUSIONS: The more visible the asthma manifestation,
      and the more recent the period to which it applies, the more reliable is the
      information provided by close acquaintances. These factors need to be taken into
      account when using information from close acquaintances in asthma mortality
      studies.

PMID- 8296252
TI  - Demographic characteristics of patients with severe life threatening asthma:
      comparison with asthma deaths.
AB  - BACKGROUND: Studies of mortality from asthma have suggested that a very severe
      asthma attack identifies a group at greatly increased risk of subsequent death
      from the disease. This study compares the demographic characteristics of
      asthmatic patients who required management in an intensive care unit for a severe
      life threatening attack between 1981 and 1987 with a group who died of asthma
      between 1980 and 1986. The outcome of the group admitted to an intensive care
      unit is described. METHODS: The groups comprised all cases aged between 15 and 49
      years arising from the Auckland Area Health Board (AAHB) population who required
      admission to an intensive care unit for asthma between 1981 and 1987 (n = 413)
      and all deaths from asthma in those aged 15 to 49 years arising from the New
      Zealand population between 1980 and 1986 (n = 466). Details of age, sex, and
      information on the day and month of the attack were collected. For the group
      requiring admission to an intensive care unit, outcome in terms of mortality and
      readmission to intensive care was determined. RESULTS: The age distributions of
      the two groups were dissimilar, with the severe life threatening attack group
      having an excess of asthmatic patients under 30 years old. The distribution of
      events by calendar month was uniform in both groups, but there was an unexpected
      increase in frequency of attacks on Sundays in both groups. Over the study
      period, mortality fell from 5.3 per 100,000 to 3.5 per 100,000 but the admission
      rate to intensive care increased from 10.8 per 100,000 to 17.9 per 100,000. At
      least 24% of asthma deaths occurring in the AAHB region during the study period
      had previously experienced a severe life threatening attack. CONCLUSIONS: The
      similarities between the groups suggest that asthmatic patients who experience
      severe life threatening attacks are likely to come from the same subgroup of the
      asthma population as those who die. The group who experience severe life
      threatening attacks are at high risk of subsequent morbidity and mortality and
      further studies may produce information relevant to reducing mortality from
      asthma.

PMID- 8296253
TI  - Controlled trial evaluation of an asthma education programme for adults.
AB  - BACKGROUND: To improve asthma control and reduce readmission rates through
      increased knowledge and the development of self management skills, a brief (three
      hour) adult education programme was developed. METHODS: The course was designed
      to improve inhaler skills and to teach how to adjust drug doses according to peak
      flow (PEF) measurements and a treatment plan. It was evaluated in a randomised
      controlled trial in 76 patients admitted to hospital for asthma by using
      questionnaires, spirometry, and home monitoring of PEF at entry and at five and
      10 months after intervention. The questionnaire provided measures of knowledge
      about asthma, self management behaviour appropriate to asthma control, asthma
      symptom frequency and severity, and psychosocial disturbance attributable to
      asthma. RESULTS: During the 10 months observation period the readmission rate for
      the educated group was one seventh that of the control group and attendance at
      accident and emergency departments also decreased. No consistent differential
      improvements were observed in spirometric results, average PEF, or mean daily
      variability of PEF. Both groups showed improvements in measures of asthma
      knowledge, behaviour, symptoms, and psychosocial disturbances. However, the
      intervention group showed a significantly greater improvement in some measures of
      asthma knowledge and self management skills. CONCLUSION: Despite minimal effect
      on measures of airway function, substantial changes in illness behaviour and use
      of health care facilities can be achieved by a brief asthma education programme.

PMID- 8296254
TI  - A district confidential enquiry into deaths due to asthma.
AB  - BACKGROUND: The aim was to establish a continuing district based confidential
      enquiry into deaths from asthma. METHODS: A confidential enquiry was conducted in
      an English health district. Subjects comprised 24 residents of the Norwich health
      district aged between 16 and 65 years who had died between 1988 and 1991 with
      asthma as the principal cause of death. RESULTS: Twenty one of the patients (88%)
      died away from hospital. Overall the routine asthma management was appropriate in
      all respects in only four patients. In five cases the drug treatment was
      considered inappropriate, in 10 cases (42%) there was no written evidence that
      the patient had received advice and education, and only six cases had a written
      management plan. In 17 patients (71%) the fatal attack of asthma developed
      rapidly (in under three hours). The medical care during the final attack was
      found to have been inappropriate in six cases. Seventeen cases (71%) had
      psychological or social factors that were considered to have been of potential
      importance. CONCLUSIONS: This study has shown the feasibility of organising a
      confidential enquiry into asthma deaths within a health district. The
      distinguishing features of such an enquiry are that it is continuing, that the
      quality of care given to those patients who died is compared against a recognised
      standard, and that there is a structured system for feeding back the conclusions
      of the enquiry to the local medical community.

PMID- 8296255
TI  - Changes in methacholine induced bronchoconstriction with the long acting beta 2
      agonist salmeterol in mild to moderate asthmatic patients.
AB  - BACKGROUND: Beta-2 agonists protect against non-specific bronchoconstricting
      agents such as methacholine, but it has been suggested that the protection
      afforded by long acting beta 2 agonists wanes rapidly with regular treatment.
      METHODS: The changes in airway responsiveness were investigated during and after
      eight weeks of regular treatment with salmeterol 50 micrograms twice daily in 26
      adult asthmatic patients, 19 of whom were receiving maintenance inhaled
      corticosteroids. The study was of a randomised, placebo controlled, double blind
      design. Airway responsiveness to methacholine was measured as PD20 by a
      standardised dosimeter technique 12 hours after the first dose, at four weeks and
      eight weeks during treatment (12 hours after the last dose of test medication),
      and at 60 hours, one week and two weeks after stopping treatment. RESULTS: There
      were no significant differences between the baseline characteristics of the two
      groups. A significant improvement in PD20 was seen at all points during treatment
      with salmeterol compared with the placebo group, with no significant fall off
      with time. PD20 measurements returned to baseline values after cessation of
      treatment with no significant difference from the placebo group. CONCLUSIONS:
      Salmeterol gave significant protection against methacholine induced
      bronchoconstriction 12 hours after administration. This protection was of small
      magnitude, but there was no significant attenuation with eight weeks of regular
      use and no rebound increase in airway responsiveness on stopping treatment in a
      group of moderate asthmatic patients, the majority of whom were receiving inhaled
      corticosteroids.

PMID- 8296256
TI  - Distribution of immunocompetent cells in the bronchial wall of clinically healthy
      subjects showing bronchial hyperresponsiveness.
AB  - BACKGROUND: Nearly all asthmatic subjects show bronchial hyperresponsiveness, in
      that the provocative concentration of histamine reducing forced expiratory volume
      in one second (FEV1) by 20% (PC20FEV1) is < or = 8 mg/ml histamine, and have
      underlying chronic inflammation of the bronchial wall mediated by T cells. The
      possible cause and effect relationship between these phenomena remains an enigma.
      As a proportion of clinically healthy subjects show bronchial
      hyperresponsiveness, this study was undertaken to determine whether they also
      show evidence of bronchial inflammation. METHODS: Bronchial biopsy specimens were
      obtained from 27 clinically healthy subjects with no history of lung disease.
      Samples were taken perioperatively before elective knee arthroscopy for sports
      injuries. Specimens were frozen and cryostat sections analysed
      immunocytochemically with monoclonal antibodies to identify the presence of T
      lymphocytes, antigen presenting cells, and the expression of HLA-DR. Double
      immunofluorescence studies were performed with monoclonal antibodies RFD1 and
      RFD7 to show the relative proportions of RFD1+ RFD7- antigen presenting cells,
      RFD1- RFD7+ mature phagocytes, and RFD1+ RFD7+ suppressor macrophages.
      Histological stains were performed to show the presence of eosinophils and mast
      cells. Three to four weeks after bronchoscopy spirometry was performed on these
      subjects to record FEV1, forced vital capacity (FVC), FEV1/FVC, and forced
      expiratory flow between 25% and 75% of vital capacity (FEF25-75). Bronchial
      hyperreactivity was recorded by determining PC20FEV1 to histamine. RESULTS: Nine
      of the 27 subjects showed bronchial hyperresponsiveness as defined by a PC20FEV1
      of < or = 8 mg/ml histamine. Segregated subjects with and without bronchial
      hyperresponsiveness showed no difference in spirometric results.
      Immunohistological analysis showed no evidence of inflammation in either group.
      Numbers of T cells, eosinophils, and mast cells were the same in both groups as
      was the expression of HLA-DR antigen. No neutrophils were observed in any
      tissues. Interestingly, reduced numbers of macrophages with the phenotype of
      antigen presenting cells (monoclonal antibodies RFD1+ RFD7-) were recorded in the
      subjects with bronchial hyperresponsiveness, who also had a significant increase
      in the proportion of RFD1+ RFD7+ suppressor macrophages. CONCLUSIONS: Up to 30%
      of selected clinically healthy subjects may have a PC20FEV1 of < or = 8 mg/ml
      histamine. This physiological trait can exist in the absence of bronchial
      inflammation. This suggests that bronchial hyperresponsiveness as currently
      defined is not dependent on immunopathological changes in the bronchial wall and
      does not necessarily promote even subclinical inflammation.

PMID- 8296257
TI  - Bronchus associated lymphoid tissue (BALT) in human lung: its distribution in
      smokers and non-smokers.
AB  - BACKGROUND: Bronchus associated lymphoid tissue (BALT) is a normal component of
      the lung's immune system in many animals and may be analogous to gut associated
      lymphoid tissue (GALT). This study aimed at assessing the nature and extent of
      BALT in human lung and determining whether its expression is induced within the
      human airway in response to smoking. METHODS: Paraffin embedded, formalin fixed
      full thickness bronchial wall sections were examined from 31 whole lung specimens
      derived from both smokers and non-smokers. Samples were taken from throughout the
      bronchial tree to include main stem bronchi, lobar bronchi and segmental bronchi,
      as well as first to third generation carinae. Standard 4 microns step sections
      were stained by haematoxylin and eosin and immunocytochemical methods to show
      foci of BALT. RESULTS: Examination of 256 airway sites detected 46 foci of BALT.
      These differed from those described in other mammals in being distributed
      throughout the bronchial tree, in being found in relation to bronchial glandular
      epithelium as well as luminal bronchial epithelium, and in lacking any
      accompanying M cells. Analysis by smoking status showed that the expression of
      BALT was significantly more common in smokers than non-smokers (82% (14/17) v 14%
      (2/14) respectively). CONCLUSIONS: The findings support the view that BALT in
      humans is an integral feature in a comparatively small proportion of lungs from
      non-smokers while being significantly more prominent in lungs from smokers. The
      tissue shows several important differences from that described in other mammals.

PMID- 8296258
TI  - How reliable is the diagnosis of lung cancer using small biopsy specimens? Report
      of a UKCCCR Lung Cancer Working Party.
AB  - BACKGROUND: A study was undertaken to investigate the accuracy of typing of a
      series of bronchial carcinomas by experienced pathologists with an interest in
      lung cancer from the examination of bronchoscopic biopsy specimens. METHODS:
      Eighty bronchial biopsy specimens showing positive results for bronchial
      carcinoma were circulated to five pathologists, who recorded diagnostic criteria
      and diagnosis for each. Diagnoses were then compared with the diagnosis agreed
      from the resection specimen corresponding to each biopsy specimen. A "non-small
      cell carcinoma, not further specified" classification group was introduced for
      small biopsy specimens. RESULTS: A diagnostic accuracy of 75% was achieved for
      squamous cell carcinomas, 66% for small cell carcinomas, and 50% for
      adenocarcinomas. There was diagnostic confusion between small cell and non-small
      cell carcinoma in less than 10% of cases. The introduction of a non-specific non
      small cell classification improved diagnostic accuracy by 10-15% for each non
      small cell tumour group. CONCLUSIONS: There are appreciable inaccuracies in
      applying the World Health Organisation's 1981 classification of lung cancer to
      the diagnosis of bronchial carcinoma from small biopsy specimens and these
      inaccuracies have been measured. They can be diminished by introducing a less
      specific "non-small cell" category for use with this sort of biopsy material.
      Care should be taken not to overinterpret small biopsy specimens in lung cancer.

PMID- 8296259
TI  - Oxygen desaturation and breathlessness during corridor walking in chronic
      obstructive pulmonary disease: effect of oxitropium bromide.
AB  - BACKGROUND: Although exercise induced desaturation can occur in patients with
      chronic obstructive pulmonary disease (COPD), little is known about its frequency
      during everyday exercise, or how it relates to dyspnoea or prior drug treatment.
      METHODS: The effects of 200 micrograms inhaled oxitropium bromide, an
      anticholinergic bronchodilator drug, on spirometric values, dyspnoea score, and
      oxygen saturation during corridor walking and cycle ergometry were studied in a
      double blind, randomised, placebo controlled study. RESULTS: Oxitropium produced
      a small increase in forced expired volume in one second (FEV1) from 0.76 (0.28) 1
      to 0.93 (0.69) 1 and in six minute walking distance from 311 (93) m to 332 (86)
      m, but did not change progressive cycle exercise duration. Resting and end
      exercise breathlessness levels were reduced in both forms of exercise after
      oxitropium. Resting oxygen saturation fell significantly after active
      bronchodilator from 92.9% (3.7%) to 92.0% (4.1%) but the nadir saturation during
      exercise was unchanged. The patients desaturated more during corridor walking
      than cycle ergometry [walking 7.8% (4.4%), cycle ergometry 2.1% (2.1%)]. Baseline
      walking distance was related to FVC, resting breathlessness and resting oxygen
      saturation (multiple r2 = 0.46) but only resting saturation correlated with end
      exercise breathlessness (r2 = -0.25). Improvements in symptoms or exercise
      performance after oxitropium could not be predicted by changes in spirometric
      indices or oxygen saturation. CONCLUSIONS: In patients with COPD arterial oxygen
      desaturation during self-paced walking is common, of greater severity than that
      during cycle ergometry, but is unaffected by inhaled oxitropium bromide. The
      factors that predict initial performance are not appropriate markers of
      functional improvement after an active bronchodilator drug.

PMID- 8296260
TI  - Bronchodilator reversibility to low and high doses of terbutaline and ipratropium
      bromide in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: There is uncertainty regarding the use of monotherapy or combination
      therapy with beta 2 agonists and anticholinergic drugs in patients with chronic
      obstructive pulmonary disease (COPD). The measurement of forced expiratory volume
      in one second (FEV1) or relaxed vital capacity (RVC) in the assessment of
      reversibility in these patients has also caused considerable debate. METHODS:
      Twenty seven patients with COPD were evaluated on two occasions. Patients
      received the following treatments in sequence: (sequence 1) low dose terbutaline
      500 micrograms, high dose terbutaline 5000 micrograms, low dose ipratropium 40
      micrograms, high dose ipratropium 200 micrograms; (sequence 2) low dose
      ipratropium 40 micrograms, high dose ipratropium 200 micrograms, low dose
      terbutaline 500 micrograms, high dose terbutaline 5000 micrograms. RVC, FEV1 and
      FVC were measured at baseline and 30 minutes after successive treatments.
      RESULTS: Values for FEV1 at baseline on the first and second study days were not
      significantly different: 0.90 (0.87-0.93) 1 v 0.90 (0.87-0.93) 1. Likewise,
      baseline values for RVC and FVC were not different. The number of patients
      showing a greater than 330 ml overall improvement in RVC was 20 of 27 for
      sequence 1 and 22 of 27 for sequence 2; similar trends were observed for FEV1 and
      FVC. For all three parameters there was a significant difference between mean
      responses to low and high doses of terbutaline when the latter was given as the
      first drug in sequence 1. When ipratropium was given first in sequence 2 there
      was, however, no significant improvement with high dose terbutaline over and
      above the response to low dose terbutaline. The latter effect was more noticeable
      with RVC than with either FEV1 or FVC. The total bronchodilator response at the
      end of each sequence was similar whether ipratropium was given first or second.
      CONCLUSIONS: The measurement of RVC, FEV1, and FVC were equally effective at
      picking up those patients who had a significant overall bronchodilator response
      to combined therapy with inhaled beta 2 agonist and anticholinergic medication.
      There was no significant benefit of adding a higher dose of terbutaline when
      ipratropium bromide had been given previously, particularly when using RVC as the
      parameter of response.

PMID- 8296261
TI  - Bronchoscopic diathermy resection and stent insertion: a cost effective treatment
      for tracheobronchial obstruction.
AB  - BACKGROUND: Major airways obstruction is a distressing cause of morbidity and
      mortality. For disease that is extensive and recurrent, there is a need for a
      safe and cost effective technique for palliation. METHODS: The results of 29
      patients with tracheobronchial obstruction (24 malignant and five benign) treated
      by diathermy resection alone or in combination with endobronchial stenting have
      been reviewed. RESULTS: The major site of obstruction was the trachea in 14, main
      carina in seven, right main bronchus in six, and left main bronchus in two
      patients. Fifteen had received other forms of treatment beforehand including
      external radiotherapy, endoscopic dilatation, and laser resection (Nd:YAG). Five
      patients required two or more treatment sessions for symptom recurrence. Ten
      patients also received additional treatment with a stent (nine) or insertion of
      gold grains (one). There were no intraoperative deaths or complications and the
      average length of stay was five days (range 2-14). Twenty eight patients reported
      immediate symptomatic relief, and objective improvement in the results of lung
      function tests was seen in eight patients whose condition was less acute and
      where preoperative lung function tests could be undertaken (average improvement
      in FEV1 of 53.1% and in FVC of 20.6%). CONCLUSIONS: Bronchoscopic diathermy
      resection is an effective and safe method for relieving the symptoms of
      tracheobronchial obstruction at appreciably less cost than laser resection.

PMID- 8296262
TI  - Measurement of exhaled nitric oxide in man.
AB  - BACKGROUND: Nitric oxide is released from pulmonary endothelial cells and
      contributes to the low pulmonary vascular resistance. The resistance pulmonary
      arteries are in close anatomical proximity to membranous airways, so it is likely
      that some pulmonary endothelial nitric oxide will enter the airspace to allow its
      measurement in the exhaled breath. METHODS: Exhaled air was collected from a
      single full exhalation and during tidal breathing. This was analysed for
      concentrations of nitric oxide, nitrogen dioxide, and carbon dioxide to give
      alveolar (FA) and mixed expired (FE) concentrations. Eight normal subjects were
      studied and laboratory air was similarly analysed using, respectively,
      chemiluminescent and infrared analysers. RESULTS: There was no relation between
      FA concentrations and the laboratory air concentrations. From the single breath,
      the ratio of (Fano/Faco2) x (Feco2/Feno) had a mean value of 0.92 (95% confidence
      interval 0.7 to 1.14). As this does not differ from unity, nitric oxide is likely
      to be derived from the same regions of the lungs as carbon dioxide. During tidal
      breathing the Feno ranged from 8.3 to 20.3 parts per billion. CONCLUSIONS: It is
      possible to measure endogenous pulmonary nitric oxide production in the exhaled
      air in man.

PMID- 8296263
TI  - Prevalence of chronic cough and phlegm among male cigar and pipe smokers: results
      of the Scottish Heart Health Study.
AB  - BACKGROUND: Previous studies investigating the effect of cigar or pipe smoking on
      the occurrence of chronic cough and chronic phlegm have reported prevalences
      among cigar and pipe smokers lying between those of non-smokers and current
      cigarette smokers. This study uses data on previous cigarette consumption,
      current cigar or pipe consumption, and biochemical markers of smoking to provide
      a detailed analysis of chronic cough and chronic phlegm among cigar and pipe
      smokers. METHODS: A total of 10,359 men and women aged 40-59 years were sampled
      for the Scottish Heart Health Study between 1984 and 1986. Prevalence of chronic
      cough and chronic phlegm among male cigar and pipe smokers (non-cigarette
      smokers) was compared with those who had never smoked, between ex-smokers of
      cigarettes and those who had never smoked cigarettes, between cigar-only and pipe
      only smokers, and by cigar or pipe consumption levels. RESULTS: In all, 463 ex
      smokers of cigarettes and 154 who had never smoked cigarettes were cigar or pipe
      smokers; 1080 had never smoked any form of tobacco. Ex-cigarette smokers smoked
      and inhaled more than those who had never smoked cigarettes. Among the ex
      cigarette smokers, cigar or pipe smokers had 1.63-1.71 times the prevalence of
      both chronic cough and chronic phlegm than those who had never smoked (1.31-1.36
      among cigar only smokers; 2.23-2.84 among pipe only smokers). A strong positive
      dose-response effect was found between the prevalence of symptoms and cigar or
      pipe consumption. CONCLUSIONS: Cigar and pipe smokers have a higher prevalence of
      chronic cough and phlegm than those who have never smoked, and the difference is
      more marked in pipe-only smokers than in cigar-only smokers. Both categories show
      a positive dose-response effect. Among cigar and pipe smokers, ex-cigarette
      smokers have a higher prevalence of symptoms than those who have never smoked
      cigarettes, which may be because they inhale more or may be attributable to
      previous cigarette smoking.

PMID- 8296264
TI  - Time trends and seasonal variation in hospital admissions for childhood asthma in
      the Athens region of Greece: 1978-88.
AB  - BACKGROUND: The aim of the study was to determine the trend and seasonal
      variation in hospital admissions for childhood asthma in the Athens region of
      Greece. METHODS: Data were obtained from hospital registries of the three main
      children's hospitals in Athens between 1978 and 1988. Children admitted with the
      diagnosis of asthma, asthmatic bronchitis, or wheezy bronchitis were included.
      The data were expressed as admission rates per 100,000 of the same aged
      population. RESULTS: There were 9795 admissions for asthma over the 11 years and
      the admission rate rose by 294%. Admissions among those aged 0-4 and 5-14 rose by
      272% and 379% respectively. Monthly admissions showed a pronounced seasonal
      variation, rising during the cold damp period in the 0-4 age group, but peaking
      around May in the 5-14 age group. CONCLUSIONS: These findings suggest that
      hospital admissions due to asthma in the Athens region have increased
      considerably since 1978, and that clear cut seasonal variations exist which are
      specific to age.

PMID- 8296265
TI  - Long term domiciliary oxygen therapy in chronic obstructive pulmonary disease.

PMID- 8296266
TI  - Thoracoscopic pericardial fenestration: diagnostic and therapeutic aspects.
AB  - The cause of cardiac tamponade is only established in 50% of cases. This problem
      is most commonly treated by pericardiocentesis alone, pericardiotomy being
      reserved for cases of recurrence and pericardiectomy for those patients
      presenting with constrictive pericarditis. A series of 16 patients treated with
      pericardial fenestration via a thoracoscope is presented. Pericardial and pleural
      biopsies were performed, together with cytological and biochemical analysis of
      the pericardial and pleural fluid where present. This procedure established the
      aetiology of effusion in all cases. In malignant pericardial effusion bleomycin
      was used for pericardial sclerosis. This resulted in fewer recurrences than in
      those patients where sclerosis was not attempted (12.5% v 60%).

PMID- 8296267
TI  - Mediastinal paraganglioma presenting as an intracardiac mass with superior vena
      caval obstruction.
AB  - A case of mediastinal paraganglioma presenting with superior vena caval
      obstruction is reported. The tumour extended into the right atrium and ventricle.
      Tru-Cut biopsy under ultrasonographic guidance was performed safely to provide a
      diagnosis before death.

PMID- 8296268
TI  - Spontaneous sternal fractures in four patients with chronic airflow obstruction
      taking corticosteroids.
AB  - Four patients with chronic airflow obstruction developed spontaneous sternal
      fractures. All had received repeated courses of high dose corticosteroids and
      three were receiving long term treatment with low dose corticosteroids. It is
      important to consider sternal fracture in the differential diagnosis when
      patients with chronic airflow obstruction present with chest pain.

PMID- 8296269
TI  - Spontaneous haemothorax: an unusual presentation of primary lung cancer.
AB  - An unusual case of spontaneous haemothorax caused by a subpleural primary lung
      cancer is reported. Tumour invasion of the pulmonary vessels and visceral pleura
      was the possible cause.

PMID- 8296270
TI  - Need for a comparative performance standard for dry powder inhalers.
AB  - The efficacy of dry powder inhalers is dependent on the inspiratory flow rate at
      which they are used. The resistance to airflow through five different dry powder
      inhaler devices was measured. The devices were shown to vary significantly, with
      the Turbohaler having the highest resistance. We suggest that the performance of
      dry powder inhalers should be assessed at comparable pressure drops producing
      clinically relevant inspiratory flow rates for each device.

PMID- 8296271
TI  - [Major and minor reforms in undergraduate education--pedagogic competence is a
      minimum factor].

PMID- 8296272
TI  - [Encouragement in community medicine].

PMID- 8296273
TI  - [Problems of small patient groups, illustrated by Williams syndrome].

PMID- 8296274
TI  - [Delivery and the infant's brain].

PMID- 8296275
TI  - [Normal labor. Is it induced as a result of subtle intrauterine inflammatory
      reactions?].
AB  - The present study was conducted in order to test the hypothesis the elevated
      cytokine levels in amniotic fluid from normal deliveries may be generated by a
      subclinical inflammatory response in intrauterine tissue. Specimens were
      collected from 38 women with normal deliveries. The levels of tumour necrosis
      factor, IL1 and IL6 in amniotic fluid samples correlated with the extent of
      inflammatory cell infiltration in specimens of the foetal membranes, placenta and
      umbilical cord. Tumour necrosis factor, IL1 and IL6 are generally produced as
      part of the inflammatory reaction and stimulate synthesis of prostaglandin. Thus
      a subclinical, intrauterine inflammatory response may play a role in initiation
      of normal parturition at term.

PMID- 8296276
TI  - [Brain injuries after transient circulatory and/or respiratory failure (cerebral
      hypoxic injury) in newborn infants].
AB  - A clinico-pathological survey of different types of cerebral hypoxic/ischemic
      injuries in foetuses and infants is presented. The lesions may occur before,
      during and after the birth. Some of them occur only in foetuses and infants less
      than two months old. The topic has been simplified in order to be useful as a
      basis for evaluating these lesions in daily diagnostic work. Cerebral
      hypoxic/ischemic injuries are frequently seen in preterm infants and term infants
      with severe cardiac anomalies. Extensive damage may be fatal or may involve
      severe permanent psychomotoric deficits in the survivors. The severity of the
      deficiencies depends on the type, location, and extent of damage. A severe lesion
      is a common cause of cerebral palsy, and a mild lesion is probably one cause of
      minimal brain dysfunction. Recent studies indicate that the lesions seen in
      preterm infants frequently occurred in utero. Thus, autopsies of perinatal deaths
      should include neuropathological examination of the brain to disclose possible
      cerebral/hypoxic damage, and its distribution, severity and age.

PMID- 8296277
TI  - [Williams-Beuren syndrome in Norway].
AB  - The author describes the Williams-Beuren syndrome and the cases of 57 patients in
      an attempt to increase awareness of the syndrome, which probably is
      underdiagnosed. Its characteristic features are a combination of a special facial
      appearance and a mental condition: The face typically shows a broad, flattened
      upper lip, small chin, and hypoplasia of teeth, often strabism, flattened nasal
      bridge and fullness around the eyes. Mentally the patients appear to be happy,
      talkative, pleasant children, who are indiscriminatingly friendly and have
      serious difficulties in concentrating. Only 53% of the patients have an affected
      heart, of whom 93% have supravalvular aortic stenosis, peripheral pulmonic
      stenoses or combinations of the two. Nine patients have had heart operations. The
      facial features in children of different age groups and races are depicted.

PMID- 8296278
TI  - [Congenital heart diseases in Sor-Trondelag. Incidence, diagnosis, course and
      treatment].
AB  - In the county of Sor-Trondelag, Norway, 145 children with congenital heart
      disease were detected among 14,194 live-born children from 1 January 1987 to 31
      December 1990. This represents an incidence of 10.2 per thousand live-born
      children. The children were followed for six to 42 months (mean 2.38 years).
      Ventricular septal defect was detected in 71 (49%) cases. Isolated ventricular
      septal defect was found in 56 (39%) cases, the muscular type being the most
      frequent (three times that of the membranous type). Other congenital defects were
      found in 28 cases (19%), either as chromosome aberrations, syndromes or
      extracardiac malformations. 13 (9%) children died. None had constant symptoms of
      congestive heart failure by the end of the study. 34 (23%) cases were referred
      from mother and child clinics. 8 (5.5%) cases were detected prenatally. Compared
      with the results of other studies, the total incidence of congenital heart
      disease was high, and mortality and incidence of other coexistent congenital
      defects were low. It seems that small and less severe heart defects were detected
      more frequently in this study. The difference was most marked for incidence of
      muscular ventricular septal defect, atrial septal defect and pulmonary stenosis.
      The probable reasons for these results are an almost complete register of cases,
      well established postnatal care and a short distance to a pediatric cardiologist.

PMID- 8296279
TI  - [Natural and synthetic surfactant in the treatment of neonatal respiratory
      distress syndrome].
AB  - The results of treatment of severe respiratory distress syndrome in premature
      infants with gestational age < or = 32 weeks are reported. During the two-year
      period 1991-92, the department participated in both the Osiris study (Exosurf)
      and the Curosurf 4 study (Curosurf). Five of the 23 infants treated with Exosurf
      died and 16 survived without major sequelae. 14 of the 25 infants treated with
      Curosurf died and six survived without major sequelae. Four of the infants
      treated with Curosurf developed severe retinopathy of prematurity. During the
      study period this complication occurred in one additional patient who was not
      eligible for inclusion in the study. The results show the need to study
      differences in the physiological effects of surfactants more closely, in order
      both to improve the basis for selection of surfactant for individual patients,
      and to define the indications for treatment. The results raise the question of
      whether such studies should continue to include control patients.

PMID- 8296280
TI  - [Medicine and human rights].
AB  - Medicine's task to promote health without inflicting harm is parallel to the two
      dimensions of human rights-"the positive rights", meaning the right of
      fulfillment of certain basic needs, and "the negative rights", meaning protection
      from harmful violations. A historical review shows that the practice of medicine
      has been an integral part of every civilization in human history, but that the
      ideas of human rights are a more recent invention of the human mind. In spite of
      old philosophical traditions about the unique value of the human being, the idea
      that all human beings are created equal and born with the same rights has only
      been truly recognized in recent centuries, and has been elaborated through
      conventions and declarations in national and international political institutions
      after World War II. At the crossroads between human rights and medicine, five
      points are high-lighted: the extensive prevalence of man-made disease, the
      relationship between medical diagnoses, ethics and law, the connection between
      healing and moral rehabilitation, the relationship between health, psychology and
      fair trials in society, and the role of physicians in conflicts of loyalty.

PMID- 8296281
TI  - [The new medical curriculum in Trondheim. Organization and planning of a new
      curriculum].
AB  - In autumn 1993, the Faculty of Medicine in Trondheim will be able to offer
      complete undergraduate medical education to 60 students per year, after 18 years
      of 3 1/2 years' education, based only on the clinical part of undergraduate
      medical school. The entire new curriculum is based on problem-based learning with
      the preclinical and the clinical part of the study totally integrated for 5 1/2
      years. Throughout the curriculum any health care problem will be analyzed in
      terms of three perspectives: the biological, the environmental and the
      behavioural. The new medical curriculum was planned as a project during which
      both teachers and students took part in planning groups organized on several
      levels. Through clinical demonstrations and a course on the doctor-patient
      relationship, the 60 students will meet patients as a natural part of their study
      from day one. In the Family Practice and in the Skills Lab they will acquire
      clinical skills during the first two years. In the fourth and fifth years the
      students spend two 8-week clerkship periods in community hospitals and community
      health practices.

PMID- 8296283
TI  - [Students' evaluation of education in psychiatry].
AB  - Students' written evaluations covering four years of education have been
      collected. According to the students' judgment, excursions, seminars involving
      presentation of patients, and teaching and problem solving in small groups were
      worthwhile. In general, the gain from lectures was regarded as low. The clinical
      rotation, predominantly based on hospital inpatient services, had been valuable
      for some, of limited value for about one half, and a waste of time for more than
      a quarter of the students. Hospital based teaching takes up most of the students'
      time and most of the institute's financial resources. According to the student's
      reports, however, it contributes only with 14% of the total gain from the course.
      Evaluations collected on several years of education provide information which
      cannot be obtained from a single assessment.

PMID- 8296282
TI  - [A new teaching program in behavioral sciences in Oslo].
AB  - The Department of Behavioural Sciences in Medicine at the University of Oslo was
      established in 1977. The teaching programme followed the same main principles
      until 1992, and took place in the third and fourth terms. Since 1992, however,
      several changes have taken place. The teaching is now given together with medical
      history during ten weeks at the end of the preclinical term. Teaching practical
      skills in doctor-patient communication is introduced in this term, and is
      continued in the first clinical year. The students work together in plenary
      seminars on the main topics presented in the lectures. The teaching is still
      concentrated on four main topics: Psychobiology, medical psychology, medical
      sociology and the doctor-patient relationship and communication. We conclude that
      the changes have improved the teaching. Written evaluation by the students
      strongly supports this conclusion.

PMID- 8296284
TI  - [Smokeless health institutions--what progress was achieved so far?].
AB  - In August 1991, the Norwegian Ministry of Health and Social Affairs distributed
      their publication Plan of Action to Achieve Smoke-free Health Institutions. The
      goal was that all health institutions in Norway should have established a smoke
      free environment for all employees before 1.1.1994. In March 1993 a questionnaire
      was sent to all health institutions. The purpose was to remind the institutions
      of the plan of action, and to evaluate the progress of the efforts to achieve
      smoke-free health institutions so far. Three types of institutions were included
      in this study: hospitals, institutions for the elderly, and psychiatric
      institutions, in all 1,437 institutions. The overall response rate was 33%. The
      response rate for the hospitals was 68%. A majority, 55%, have decided to
      establish a smoke-free environment for their employees. About two thirds of the
      institutions who had not made such a decision do not have any plans to do so. It
      is concluded that this study indicates a demand for further action in order to
      establish smoke-free health institutions in Norway. Stronger involvement seems to
      be needed, particularly on the part of the municipalities and countries, as
      owners of the institutions.

PMID- 8296286
TI  - [Norwegian physical therapy in crisis?].

PMID- 8296285
TI  - [Perinatal care yesterday, today, tomorrow--which way does the pendulum swing?].
AB  - Based on knowledge of foetal physiology and circulation, time for cord clamping
      and placement of the infant after delivery, we discuss the conditions around ABC
      (Alternative Birth Care) deliveries, the baby-friendly initiative and early
      discharge from the maternal ward. When ABO-incompatibility is present, the number
      of infants needing phototherapy is doubled. With use of a reflectometric
      bilirubin determination and new phototherapy units, diagnosis and treatment can
      be performed at home. In the wake of high technology, the introduction of new and
      the reintroduction of old routines, it is easy to forget the sensible dimensions
      of the interaction between mother and infant. These are probably the most
      important factors connected to the development of mother and child interaction
      and the infant's way of managing its future life.

PMID- 8296287
TI  - [Carvedilol--2 companies introduce the same antihypertensive agent].

PMID- 8296288
TI  - [Hospitalization with intrauterine fetal death].

PMID- 8296289
TI  - [Wake up].

PMID- 8296290
TI  - [Patients rights?].

PMID- 8296291
TI  - [Information on epicrisis to be given to the patient].

PMID- 8296293
TI  - [Norwegian physicians].

PMID- 8296292
TI  - [Will politicians smoke at Soria Moria in the year 2000?].

PMID- 8296294
TI  - [Are physicians bad lecturers?].

PMID- 8296295
TI  - [Weapons without control--violence without end: America's internal war].

PMID- 8296296
TI  - [Do we medicate general experiences? Some thoughts on the role of a health center
      in a medicated community].

PMID- 8296297
TI  - [An outbreak of equine arteritis virus infection in a riding school].
AB  - A major part of the residing horses and ponies of a riding school in Noord
      Holland became affected by a febrile disorder that included anorexia, depression,
      conjunctivitis, urticaria, edema of the legs and laborious locomotion. All
      remaining horses fell ill within one week. Based on the clinical symptoms the
      disorder was diagnosed as vasculitis. With serology the causative agent of the
      disorder appeared to be equine arteritis virus.

PMID- 8296298
TI  - [Impotentia coeundi and penile extension in steers].
AB  - Penis extension (emissio penis) depends on the length of the penis and on the
      relaxation of the retractor muscle of the penis. When the relaxation is
      insufficient, penis extension is at its smallest just before intromission takes
      place. In severe cases this can lead to impotence (impotentia coeundi). Whether
      this occurs depends on the animal's libido and mating behaviour and on external
      factors. Genetic factors play a role in emissio penis.

PMID- 8296299
TI  - [Fecal analysis of beef cattle for the presence of Escherichia coli serotype
      O157:H7].
AB  - A total of 550 faecal samples of cattle was examined on the presence of
      Escherichia coli serotype O157:H7 using a method comprising a selective
      enrichment and isolation medium. Escherichia coli O157:H7 was not isolated from
      any of the samples tested.

PMID- 8296300
TI  - [Current developments in veterinary public health. Veterinarians scrutinize stock
      in-trade].

PMID- 8296301
TI  - [Drops in the neck].

PMID- 8296302
TI  - [The Society for the Promotion of Veterinary Medicine in The Netherlands].

PMID- 8296303
TI  - [Dubious advertising in Tijdschrift voor Dierengeneeskunde].

PMID- 8296304
TI  - [Veterinary medicine education].

PMID- 8296305
TI  - In situ preparation of rat tracheal basal cells.
AB  - The primary function of basal cells is to attach columnar epithelium to the basal
      lamina. They may also have limited stem cell potential, but very little is known
      of other biological functions. Basal cells lie on the basal lamina beneath the
      ciliated and secretory cells and do not reach the surface of the epithelium. The
      position of the cell beneath the ciliated and secretory cell epithelium makes
      their in situ study difficult. In order to further aid in the study of basal
      cells, we have developed an in situ preparation technique in which ciliated and
      secretory cells are removed. Treatment of rat tracheas with a 20 mM Na2 EDTA
      solution, pH 7.4, results in partial removal of columnar epithelium from the
      basal lamina. The percent of denuded columnar epithelial cells per mm of basal
      lamina is 43.9 +/- 7.8% at 60 min, 47.6 +/- 8.4% at 90 min, and 52.6 +/- 2.7% at
      120 min. The viability of the exposed basal cells was the same at both 60 and 90
      min of treatment (79.4 +/- 7.8 and 78.0 +/- 8.5, respectively). Morphologically,
      the exposed basal cells are attached to the basal lamina by hemidesmosomes and
      are similar to those in the intact animal.

PMID- 8296306
TI  - Patterns of cellular proliferation and airway branching in cultured fetal hamster
      lung explants.
AB  - Lungs were removed from hamsters at gestational day 12 and cultured in BGJb
      medium under the following conditions: (1) alone, (2) with 5% fetal bovine serum
      (FBS), (3) with defined additives (with and without vitamin A), and (4) with
      defined additives but lacking both epidermal growth factor (EGF) and vitamin A.
      Patterns of cell proliferation were determined by immunochemical labeling for
      bromodeoxyuridine (BrdU) and airway branching was evaluated in each explant.
      After 4 days in BGJb alone, an orderly but limited branching pattern occurred,
      and labeling was greater in the epithelium than in the connective tissue. With
      FBS a relatively normal branching pattern occurred, and labeling was nearly
      equivalent in connective tissue and epithelium. With defined additives the
      connective tissue was heavily labeled in the compact region supporting the
      distorted bronchioles and in the loose flange at the periphery; removing only
      vitamin A did not alter these patterns. Removing both vitamin A and EGF caused an
      extensive but distorted epithelial branching pattern that extended to the
      periphery of the explant (a flange of loose connective tissue did not form); BrdU
      labeling was sparse. These results indicate that EGF played a major role in
      contributing to alterations in the growth and development of fetal hamster lung.

PMID- 8296307
TI  - Morphogenesis and origin of fibrous long-spacing collagen fibers in collagenase
      treated mouse skin tissues.
AB  - Morphogenesis and origin of fibrous long-spacing collagen (FLS) fibers in newborn
      mouse skin tissues treated with collagenase were examined using ultrastructural
      observation, morphometry, histochemical methods, and immunoelectron microscopy.
      The enzyme caused both the partial destruction of basal laminae and the formation
      of abundant FLS fibers in the dermal matrix. The fibers were usually distributed
      in the vicinity of basal laminae in the capillaries or basal layer cells. The
      fibers were characterized by the cross-striated dark bands with about 91 nm
      periodicity and longitudinally aligned filaments with a diameter of about 6.5 nm.
      The dark bands of FLS fibers were often continuous with the basal laminae.
      Histochemical results showed that the dark bands contained the similar
      mucopolysaccharides which were involved in the basal laminae. Immunoelectron
      microscopic results showed that laminin was present in the dark bands as well as
      in the basal laminae, and that type VI collagen was located in the filaments of
      FLS fibers. These results suggest that the dark bands are formed by products
      similar to basal laminae and that the products were precipitated on type VI
      collagen-contained filaments with periodic intervals of about 91 nm. Morphometric
      examination revealed that there was no differences in ultrastructure between FLS
      fibers of a collagenase-treated mouse and those of a human neural tumor.

PMID- 8296308
TI  - Structural study of the frog Rana temporaria larval stomach.
AB  - The gastric wall of Rana temporaria tadpoles consists of a well-developed mucosa
      and thin muscular and serosa layers. Three cellular types--mucous, ciliated and
      endocrine cells--make up the lining epithelium. Different types of endocrine
      cells exist. Argyrophylic endocrine cells can be recognized in semithin sections
      of plastic-embedded material while non-argyrophylic endocrine cells can only be
      identified under the electron microscope. Glands are composed mainly of well
      differentiated oxyntic cells and, occasionally, scarce endocrine cells. Oxyntic
      cells show abundant mitochondria and smooth endoplasmic reticulum, but do not
      contain zymogen granules as do those present in adults. Secretory canaliculi with
      microvilli are also well-developed. The lamina propria contains numerous vascular
      sinuses and nerve bundles which innervate the endothelium and some endocrine
      cells. The neuroendocrine regulation of frog gastric functions seems therefore to
      have developed in young tadpoles. Nerve fibers also innervate the muscular
      propria, which is composed of a single layer of smooth muscle cells. Underlying
      the muscle, connective fibers and a flattened layer of mesothelial cells make up
      the serosa. In summary, the structure of the frog larval stomach shows a well
      differentiated histological pattern, especially referring to surface epithelium
      and glands. Some of the histological traits will also be present in adult frogs
      while others are characteristic of the tadpole's stage.

PMID- 8296309
TI  - Spatial organization of microtubules and microfilaments in larval and adult
      salivary glands of Drosophila melanogaster.
AB  - We examined the distribution of microtubules and microfilaments by conventional
      fluorescence microscopy and laser scanning confocal microscopy in larval and
      adult salivary glands of Drosophila melanogaster. The cells of the larval
      salivary gland epithelium were characterized by the same spatial distribution of
      microfilaments, whereas microfilament localization was more complex in adult
      salivary glands, showing some regional differentiation. Microtubules distributed
      throughout the cell cytoplasm of the larval salivary glands, whereas in adult
      glands they were mostly observed in the basal or apical cytoplasm of the cells.
      These observations were related to the secretory process and the mechanism of
      saliva discharge.

PMID- 8296310
TI  - Immunohistochemical localization of lactoferrin in bovine exocrine glands.
AB  - The localization of lactoferrin (LF) was studied in bovine exocrine glands by the
      peroxidase-antiperoxidase method. In general, LF immunoreactivity was
      demonstrated in most of the serous demilunes of the mixed glands and in some but
      not all acinar cells of the serous glands. LF was not detected in the acinar
      cells of the mucous glands. LF immunoreactive cells were seen in the nasal and
      tracheal glands. The lacrimal and mammary glands were stained intensely, while
      the sweat glands were not stained. In the major and minor salivary glands, LF
      immunoreactivity was demonstrated in the serous demilunes and acini of the mixed
      glands and in some serous cells of the pure serous parotid gland. LF
      immunoreactivity was not seen in the gastrointestinal tract and pancreas, but the
      serous gland in the lamina propria of the bile duct was stained positively. In
      the male reproductive tracts, the prostate and bulbourethral glands were stained
      positively, but the vesicular gland was negative. In the female reproductive
      system, the uterine and Bartholin glands, the epithelial cells of the cervix and
      ampulla of the uterine tube reacted positively. However, the lesser vestibular
      gland did not react for LF. The present findings, that LF was demonstrated in the
      exocrine glands located mainly in the gateways of the digestive, respiratory and
      reproductive systems, may morphologically support the antibacterial role of LF.

PMID- 8296311
TI  - Cancer policy framework for: public health assessment of carcinogens in the
      environment.
AB  - Cancer remains at the forefront of public health concerns in the United States
      and throughout the world. Over the past 20 years a wide range of federal agencies
      and other organizations have been involved in developing policy statements,
      classification strategies, and assessment methods to address carcinogenesis and
      health risks. Each of these documents was developed in response to issues
      confronted by those organizations in pursuing their mission, often as a direct
      function of legislative mandates. In pursuing its mandated responsibilities, the
      Agency for Toxic Substances and Disease Registry (ATSDR) must address public
      health concerns associated with exposure to carcinogens in the context of all
      available relevant information. This information includes both technical data as
      well as science policy positions adopted by the range of organizations with
      programs germane to the assessment and/or regulation of carcinogens. Because of
      distinct differences in perspective, practice, and policy dictated by the
      mandated activities of these organizations and the rapidly evolving understanding
      of carcinogenesis, apparently divergent positions may be reflected in their
      conclusions. The differences outlined above, coupled with requests from the
      public, other agencies, and the private sector for a statement reflecting the
      Agency's position on science and science policy issues related to cancer,
      prompted the development of this policy. This document is intended to serve as a
      framework to guide the Agency in its programs and actions regarding carcinogens
      and to harmonize such efforts with those of other federal agencies and relevant
      organizations. This framework reflects an assessment of current practice within
      the Agency and defines the appropriate roles of conclusions derived by other
      groups, professional judgment, and emerging scientific principles in ATSDR's
      public health assessments of exposures to carcinogens. This Cancer Policy
      Framework is not intended to encompass the development of operational guidelines
      per se, although the Agency recognizes the utility of such efforts. A central
      theme of this Cancer Policy Framework is the use of risk analysis as an
      organizing construct based on sound biomedical and other scientific judgment to
      define plausible exposure ranges of concern rather than single numerical
      conclusions that may convey an artificial sense of precision. The development and
      use of innovative tools for exposure and dose response assessment (with
      particular emphasis on molecular epidemiology) are also endorsed.

PMID- 8296312
TI  - Workshop on toxicological data quality indicators.

PMID- 8296313
TI  - Teratogenic potential of FD&C Red No. 3 when given by gavage.
AB  - FD&C Red No. 3 (erythrosine) is a commonly used food additive. As part of a
      series of studies on the potential fetal developmental effects of food colors,
      FD&C Red No. 3 was administered by gavage to pregnant Osborne-Mendel rats at
      daily dose levels of 15, 30, 100, 200, 400, or 800 mg/kg on days 0-19 of
      gestation. Control animals were given distilled water by gavage. On gestation day
      20, the animals were euthanized and cesarean sections were performed. During the
      entire treatment period, feed consumption by the animals given 400 mg/kg doses
      was increased significantly; the increases in the animals given 30 or 800 mg/kg
      were of borderline significance. The only significant increase in maternal weight
      gain, on days 0-7 in the animals given 30 mg/kg, was considered a random
      occurrence. No dose-related changes were seen in maternal clinical findings,
      implantations, fetal viability, or fetal size (weight and length). No fetal
      terata were seen, and neither skeletal nor visceral development was affected.
      FD&C Red No. 3 was neither fetotoxic nor teratogenic at 800 mg/kg when given by
      gavage.

PMID- 8296314
TI  - Effect of small doses of ethylene glycol monomethyl ether on the
      acetylcholinesterase and delta-aminolevulinic acid dehydratase activity in
      erythrocytes, blood and bone marrow of rats.
AB  - The effect of small doses of ethylene glycol monomethyl ether (EGMME) on the
      activity of acetylcholinesterase (ACHE) in erythrocytes and whole blood as well
      as on the delta-aminolevulinic acid dehydratase (ALA-D) in blood and bone marrow
      was studied in Wistar rats. Significant reduction in the activity of both enzymes
      was noted three days after ip administration of 200 mg/kg b.w. EGMME whereas
      seven days later the activity of both enzymes returned to the control levels.
      Activity of ALA-D in blood appeared to be most sensitive to EGMME, and reacted
      even to the lowest dose, which did not significantly alter activity of ACHE or
      ALA-D in bone marrow. Haematological parameters in all treated groups remained
      unaltered.

PMID- 8296315
TI  - Effects of acute and subchronic exposure of topically applied fullerene extracts
      on the mouse skin.
AB  - The recent discovery that fullerenes (C60) can be produced in macroscopic
      quantities has sparked much interest in the chemistry of this unusual molecule.
      Concerns have also arisen about the potential carcinogenic effects of this
      molecule. We have addressed the potential acute and subchronic toxic effects of
      fullerenes applied in benzene on the mouse skin. The acute toxic effects measured
      in this study included epidermal DNA synthesis and the induction of ornithine
      decarboxylase activity in the epidermis. At the topical dose of fullerenes used
      in these studies (i.e., 200 micrograms), we found no effect on either DNA
      synthesis or ornithine decarboxylase activity over a 72 hour time course after
      treatment. The subchronic effects of the fullerenes as a mouse skin tumor
      promoter was assessed by repeatedly applying the chemical to the skin after
      initiation with the polycyclic aromatic hydrocarbon, 7,12-dimethylbenzanthracene
      (DMBA). Repeated administration of the fullerenes for up to 24 weeks post
      initiation did not result in either benign or malignant skin tumor formation,
      whereas promotion with the phorbol ester, 12-O-tetradecanoyl-phorbol- 13-acetate
      (TPA) resulted in the formation of benign skin tumors. Our data indicate that
      fullerenes applied in benzene at a likely industrial exposure level do not cause
      acute toxic effects on the mouse skin epidermis.

PMID- 8296316
TI  - Carcinogenicity of TCDD in laboratory animals: implications for risk assessment.

PMID- 8296317
TI  - Catalytic selectivity of human cytochrome P450 enzymes: relevance to drug
      metabolism and toxicity.
AB  - About 30 different human cytochrome P450 (P450) enzymes have now been
      characterized in considerable detail. It is possible to elucidate their catalytic
      specificities towards drugs, steroids, carcinogens, and other potential
      substrates with in vitro assays. It is also possible to ascertain the levels of
      individual P450 enzymes in humans with the use of drugs, after appropriate assay
      validation. The ability to discern catalytic selectivity and levels of P450
      enzymes within individuals offers considerable potential in drug development,
      prevention of undesirable drug-drug interactions, and understanding the etiology
      of diseases resulting from exposure to potentially toxic and carcinogenic
      chemicals.

PMID- 8296318
TI  - Lipid peroxidation in the adrenal glands of male rats exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD).
AB  - This study was performed to determine whether TCDD (50 micrograms/kg; single oral
      dose) could induce adrenal microsomal lipid peroxidation, which might be
      correlated to decreased levels of cytochrome P-450 and 21-hydroxylase activity.
      The amount of malondialdehyde (MDA) formed was significantly higher than controls
      at days 1 through 5 following TCDD treatment. Microsomal cytochrome P-450 levels
      were depressed after lipid peroxidation at days 1, 3, and 5, and 21-hydroxylase
      activity decreased at day 5 after TCDD treatment. This study shows that TCDD
      stimulates adrenal microsomal lipid peroxidation which is associated with
      decreased cytochrome P-450 levels and 21-hydroxylase activity.

PMID- 8296319
TI  - Comparison of aniline hydroxylation by hemoglobin and microsomal cytochrome P450
      using stable isotopes.
AB  - Hemoglobin (Hb) and cytochrome P450 carry out aromatic ring hydroxylation of
      aniline. In the presence of reductants and Hb, para- and ortho-aminophenol were
      formed. Under [18O]O2, 100% of product was labeled; no incorporation occurred
      with [18O]H2O. Deuterium (1.9%) was detectable in p-aminophenol formed from p
      [2H]aniline by Hb, as compared with 6% retention observed with cytochrome P450.
      These observations are consistent with a mechanism for Hb-dependent reaction
      involving formation of an iron-oxo complex competent to hydroxylate substrate. Hb
      mediated reactions may represent a source of extrahepatic metabolism since Hb is
      a major carrier for small organic molecules. The similarities of P450- and Hb
      mediated aniline hydroxylation using stable isotopes preclude their use as in
      vivo probes.

PMID- 8296320
TI  - Theobromine toxicity on Sertoli cells and comparison with cocoa extract in male
      rats.
AB  - The target cell(s) of theobromine toxicity on rat testes and reproductive
      toxicity induced by pure theobromine and cocoa extract are evaluated in the
      present studies. Theobromine (500 mg/kg x 7 days) inhibited body weight gain in
      treated rats. Decreased cauda epididymal sperm reserve (38%), seminiferous tubule
      fluid (STF) volume (33%), lactate concentration in STF (22%), inhibition of
      binding activity of androgen binding protein (ABP, 21%) and reduced ABP content
      in STF were also observed in theobromine-treated animals. Cocoa extract
      containing an equivalent amount of theobromine did not produce significant
      toxicity in treated rats. Theobromine concentrations in serum and testes from
      pure theobromine-treated rats were 1.8- and 1.6-fold higher, respectively, than
      that in rats treated with cocoa extract. The results support Sertoli cells as the
      primary target cells of theobromine toxicity. The lower theobromine
      concentrations in serum and testes of cocoa extract-treated rats could account
      for the lower toxicity in these animals.

PMID- 8296321
TI  - Evaluation of the genotoxic potential of selected anti-AIDS treatment drugs at
      clinical doses in vivo in mice.
AB  - Six anti-AIDS drugs were assessed for in vivo genotoxicity and cytotoxicity at
      human clinical doses with the mouse bone marrow micronucleus assay. These
      included four dideoxynucleosides (azidothymidine, dideoxycytidine,
      dideoxyadenosine, and dideoxyinosine), an anthracycline antibiotic (doxorubicin),
      and a chelating agent (D-penicillamine). Cytological analysis of the mouse bone
      marrow cells revealed: (i) The dideoxynucleosides and D-penicillamine failed to
      induce significant number of micronuclei, and except for one of the five doses of
      dideoxyinosine, none of the dideoxynucleosides were cytotoxic at the doses
      tested. (ii) Doxorubicin induced micronuclei in a dose-dependent manner which was
      statistically significant at 4-times the clinical dose but was not cytotoxic at
      any of the doses tested.

PMID- 8296322
TI  - Heterogeneity in the amount of ionic cadmium necessary to elicit cell death in
      independent cultures of human proximal tubule cells.
AB  - Eleven separate isolates of human renal proximal tubule cells (HPT) were analyzed
      for toxic response to ionic cadmium exposure over a 16-day period in vitro. This
      study demonstrates a heterogeneous response to Cd2+ exposure in isolates from
      different individuals with some individuals nearly 3-times more sensitive to
      ionic cadmium exposure than others. There was no apparent correlation to the
      race, sex or age of the individuals in the response to cadmium. In addition,
      readily identifiable culture artifacts, i.e., culture age, passage number, had no
      influence on the response to Cd2+ exposure and the different isolates had
      homogeneous baseline HPT properties and morphology. This difference in response
      to Cd2+ may reflect a heterogeneous response within the human population to
      cadmium exposure.

PMID- 8296323
TI  - Organ distribution of silver and the effect of silver on copper status in rats.
AB  - Tissue distribution of silver, alteration in tissue concentration of copper, zinc
      and iron, as well as changes in serum ceruloplasmin (CP) status were investigated
      in Fischer 344 rats after intraperitoneal (i.p.) administration of silver (9.3
      mumol Ag/kg body wt.) as silver nitrate alone or combined with zinc (46.5 mumol
      Zn/kg) as zinc sulfate once a day for six successive days. Silver deposited in
      all the tissues examined, particularly in the pancreas, showing silver
      concentration in the serum, kidney, heart and lung to be significantly increased
      by simultaneous injection of zinc, while zinc concentration in the liver,
      pancreas and heart was significantly affected by silver. The most prominent
      effect of silver administration was observed in the copper status. As the result
      of altered copper metabolism by silver administration, copper concentration in
      the liver, pancreas and kidney was significantly changed, and serum copper
      concentration and CP oxidase activity were decreased to 60% and 25% of the
      control value, respectively. However, immunoblot analysis of serum CP in silver
      treated groups showed only a slight decrease in protein levels, suggesting that
      most of the CP existed as an oxidase inactive apo-form. Simultaneously
      administered zinc hardly affected such changes. These results indicate that
      silver administration causes a disturbance of copper metabolism, and that zinc
      hardly plays a protective role against such changes.

PMID- 8296324
TI  - The effects of ozone exposure on lactate dehydrogenase release from human and
      primate respiratory epithelial cells.
AB  - Ozone is the most persistent, wide-spread air pollutant in the United States.
      Over one half of the population of the US lives in cities or suburban areas which
      do not meet the National Ambient Air Quality Standard for ozone which is 0.12 ppm
      averaged over 1 h. Controlled laboratory exposures of human subjects have shown
      that ozone exposure produces decreased pulmonary function, hyperresponsiveness to
      inhaled methacholine, inspiratory pain, and airway inflammation as assessed by
      bronchoalveolar lavage. However, the cellular mechanisms responsible for such
      effects are incompletely known. The present study examined the effects of ozone
      exposure at 0.50 ppm for 3 h on three types of cultured respiratory epithelial
      cells; primary cultures of human nasal cells and primate bronchial cells, and the
      A549 type II pneumocyte-derived cell line. Cells were grown to confluent
      monolayers in plastic 6-well plates and then exposed to ozone or filtered air on
      a tilting platform over a heated water bath. Lactose dehydrogenase release was
      significantly increased following ozone exposure of all cell types; a 75%
      increase from human nasal cells (P = 0.0002), a 79% increase from primate
      bronchial cells (P = 0.003), and a 69% increase from A549 cells (P = 0.02). These
      data suggest that even brief ozone exposure causes membrane injury to cultured
      human respiratory epithelial cells.

PMID- 8296325
TI  - Role of glutathione S-transferase isoenzymes in cisplatin-induced nephrotoxicity
      in the rat.
AB  - cis-Diamminedichloroplatinum(II) (cisplatin) is an effective antitumor agent but
      causes dose-dependent nephrotoxicity. We examined the changes of glutathione S
      transferase (GST) isoenzymes in the rat kidney after cisplatin administration.
      Renal GST-alpha activity was decreased to 33.4% of the control level and GST-mu
      activity was increased 1.9-fold after cisplatin administration. These results
      were confirmed by affinity chromatography of rat renal GST isoenzymes. Our
      results showed that changes of GST isoenzymes were associated with cisplatin
      induced nephrotoxicity. We examined whether GST isoenzymes leaked into the urine
      by proximal tubular damage could provide a useful marker of cisplatin-induced
      nephrotoxicity. The total GST and GST-mu activities in urine correlated well with
      the changes of BUN, which closely parallels the course of nephrotoxicity after
      cisplatin administration. Our results indicated that renal GST-mu activity was
      decreased by cisplatin, and although GST-mu activity increased as a compensation
      mechanism, nephrotoxicity still appeared because of differences in substrate
      specificity between these two isoenzymes.

PMID- 8296326
TI  - An electroretinogram protocol for toxicological screening in the canine model.
AB  - A five-step electroretinogram protocol was developed for the dog to be used as a
      painless screening test for ocular effects of drugs or pesticides. Standard
      conditions of frequency band width, stimulus intensity, dark adaptation time and
      non-confounding anesthesia method were selected to allow analysis of wave
      components. The protocol demonstrated an acceptable level of inter-subject
      variability for compiling an age appropriate database, and for the detection of
      possible retinal component toxicities in chronic dog studies. This
      electrophysiologic procedure may serve to corroborate biochemical, clinical and
      pathology data, in establishing a compound's no-observable-effect-level (NOEL).

PMID- 8296327
TI  - Inhibitory effect of crocetin on intracellular nucleic acid and protein synthesis
      in malignant cells.
AB  - The possibility that dietary intake of diverse naturally occurring compounds may
      influence the occurrence of cancer is receiving considerable scientific
      attention. Previously, it was reported that an extract (Crocus sativus), which
      contains carotenoids, had an antitumor effect and inhibited colony formation and
      nucleic acid synthesis by malignant human cells. Epidemiological and experimental
      research has indicated that carotenoids might act as antitumor agents. We have
      studied crocetin, a carotenoid isolated from saffron, which has been shown to
      have biological activity. In our experiments we utilized three malignant human
      cell lines: HeLa (cervical epitheloid carcinoma), A549 (lung adenocarcinoma) and
      VA13 (SV-40 transformed fetal lung fibroblast) cells. The effect of crocetin on
      colony formation and cellular DNA, RNA and protein synthesis in these cells has
      been examined. Incubation of these cells with crocetin for 3 h caused a dose
      dependent inhibition of nucleic acid and protein synthesis. Crocetin also had a
      dose-dependent inhibitory effect on DNA and RNA synthesis in isolated nuclei and
      suppressed the activity of purified RNA polymerase II.

PMID- 8296328
TI  - Effects of m-xylene on rat nasal cytochrome P450 mixed function oxidase
      activities.
AB  - The effect of m-xylene on the rat nasal cytochrome P450 (P450) mixed function
      oxidase system was analyzed in vitro utilizing microsomes isolated 2, 12, and 24
      h following intraperitoneal administration of this solvent in vivo. For
      comparative purposes, pulmonary and hepatic activities were also measured.
      Benzyloxyresorufin O-deethylation (BROD) and ethoxyresorufin O-deethylation
      (EROD), catalytic activities linked with P450 isozymes IIB1 and IA1,
      respectively, were inhibited in nasal tissue at all times following m-xylene
      administration. Pulmonary tissue mimicked this m-xylene-dependent inhibition of
      BROD activity but did not display significant inhibition of EROD activity. In
      contrast, m-xylene caused a dramatic induction of both BROD and EROD activity in
      hepatic tissue. The metabolism of a third P450 substrate, cyclopentadienyl
      manganese tricarbonyl (CMT), was also analyzed. m-Xylene caused significant
      inhibition of CMT metabolism at all time points in both nasal and pulmonary
      microsomes but was without effect on hepatic microsomal metabolism of this
      compound. These data show an inhibitory effect of m-xylene on rat nasal and
      pulmonary but not hepatic cytochrome P450-dependent metabolism.

PMID- 8296329
TI  - The sexuality connection in reproductive health.
AB  - Sexuality and power relations based on gender are relevant to researchers,
      policymakers, and service providers in the reproductive health field, because
      they underlie virtually all of the behaviors and conditions that their programs
      address. Yet, a review of conventional treatments in the demographic and family
      planning literature reveals that, when they consider these topics at all,
      researchers typically adopt narrow definitions of sexual behavior and focus
      almost exclusively on risks of pregnancy and disease. This article proposes an
      analytic framework as a guide to researchers and family planning providers. It
      relates four dimensions of sexuality to reproductive health outcomes and
      concludes that family planning policies and programs should address a broader
      spectrum of sexual behaviors and meanings, consider questions of sexual enjoyment
      as well as risk, and confront ideologies of male entitlement that threaten
      women's sexual and reproductive rights and health.

PMID- 8296330
TI  - Problems related to schoolgirl pregnancies in Burkina Faso.
AB  - A qualitative study of pregnancy among schoolgirls in a small town in Burkina
      Faso was conducted that described the situation of pregnant students and their
      motherhood, their social environment, and the situation of their children. The
      analysis of findings revealed four main factors that influenced students'
      pregnancies: lack of contraceptive knowledge, ambiguous feelings about pregnancy
      and contraception, conflicting messages concerning the reproductive role of young
      women, and the girls' low self-esteem in their interaction with older,
      experienced male partners. The study revealed that existing family planning
      programs fail to address the needs of the sexually active school-age population.
      Recommendations are made concerning sex education and service delivery.

PMID- 8296331
TI  - The impact of the Healthcom mass media campaign on timely initiation of
      breastfeeding in Jordan.
AB  - Initiation of breastfeeding within several hours after a child's birth increases
      the likelihood of exclusive breastfeeding and longer duration of breastfeeding.
      However, common beliefs among mothers and health-care providers and routine
      hospital practices can constrain timely breastfeeding initiation. This article
      examines the impact of a mass media breastfeeding campaign in Jordan within the
      context of other activities occurring during and after the child's birth. The
      campaign had a positive impact on all mothers' knowledge, and on timely
      initiation of breastfeeding for home and public hospital deliveries, but not for
      those in private hospitals. The findings indicate that a communication campaign
      can bring about change in breastfeeding initiation behavior, but that providing
      mothers with information should be but one part of an integrated program to
      ensure that hospital and midwife policies and practices support timely
      initiation.

PMID- 8296332
TI  - Levels and causes of maternal mortality in southern India.
AB  - Most studies of maternal mortality are hospital based. However, in developing
      countries, where many such deaths take place in the home, hospital statistics do
      not reflect the true extent of maternal mortality. Furthermore, the socioeconomic
      and demographic factors and health behavior affecting maternal mortality are
      rarely known. A study conducted in 1986 in South India demonstrates a new
      approach to investigating maternal mortality that combines the collection of
      information from hospital and health-facility records, field surveys, and case
      control studies. The findings from this study indicate that there were 7.98
      maternal deaths per 1,000 live births. Approximately one-half of the deaths
      occurred in the home or on the way to the hospital. Maternal deaths accounted for
      36 percent of mortality for women of reproductive age. Analysis reveals that many
      of these deaths were preventable and that significant differentials existed with
      regard to demographic, social, and behavioral factors between the cases of
      maternal deaths and the controls.

PMID- 8296333
TI  - The effectiveness of intravaginal misoprostol (Cytotec) in inducing abortion
      after eleven weeks of pregnancy.
AB  - At Maputo Central Hospital in Mozambique, intravaginal misoprostol, a PGE2 methyl
      analogue, was used by 169 women whose request for interruption of pregnancy had
      been approved. The drug was used by women who had completed between 12 and 23
      weeks of gestation. The initial dose was 800 micrograms, repeated 24 hours later
      if abortion had not occurred or was not in progress. The treatment was considered
      a failure when abortion was not advanced by 48 hours after the initial dose, and
      curettage was performed in all but one of such cases. During the course of the
      study, the dosage was successively reduced to 600, 400, and 200 micrograms.
      Abortion was successfully induced in 154 women (91.1 percent); there were 10
      failures (5.9 percent), and five women (3.0 percent) dropped out of the study.
      The mean time from initial dose to abortion was 14.3 hours. No significant
      association of success rate and time from dosage to expulsion was found with age,
      parity, previous abortion, or gestational age. Preventive vacuum aspiration of
      the uterine cavity was carried out on all subjects.

PMID- 8296334
TI  - Tanzania 1991/1992: results from the Demographic and Health Survey.

PMID- 8296335
TI  - [Determination of the severity of bodily injuries with infectious complications].

PMID- 8296336
TI  - [Micromorphology of injuries to soft tissues of the scalp in the acute period of
      craniocerebral trauma with various levels of consciousness].
AB  - Presents a comparative analysis of vascular and tissue reactions at the site of
      injuries to soft integument of the hairy part of the head in the acute period of
      craniocerebral injury in various forms of consciousness disturbances. Analyzes
      the time course of vascular changes in various topographic zones of soft
      integument of the head during 13 days, divided into 7 intervals, of the acute
      period of craniocerebral injury.

PMID- 8296337
TI  - [Characteristics of double shot (doublet) from traces of shot products in the
      targets].

PMID- 8296338
TI  - [Possibility of detecting phenobarbital in biological fluids after taking a
      therapeutic dose].
AB  - The authors have examined the possibility of detecting phenobarbital in normal
      subjects' urine after a single intake of a therapeutic dose and in experimental
      animals' (rats) organs after a single intake and after a course of administration
      of the drug. They came to a conclusion that the positive results of the
      qualitative method of the drug detection in biologic fluids, particularly in case
      of death at the site of the accident, are not sufficient for the expert to
      substantiate the cause of death.

PMID- 8296339
TI  - [New potentials for scanning electron microscopy in the study of hair].
AB  - Presents data on differentiation by scanning electron microscopy of pigment
      eumelanin of human hair and of some animals' hair morphologically similar to
      human, as well as of hair core disks in closely related animals. The method was
      used in expert evaluations.

PMID- 8296340
TI  - [Analysis of errors allowable in conducting forensic chemical studies].
AB  - The authors have analyzed methodologic errors made by chemical experts in records
      of forensic chemical investigations selected at random. The major errors are
      classified and their frequency determined in relation to the complexity of the
      task. Suggestions are made aimed at improvement of the quality of forensic
      chemical investigations.

PMID- 8296341
TI  - [Infrared spectrometry in the practice of forensic medicine].
AB  - Presents some aspects of using infrared spectrophotometry in forensic medical
      diagnosis of poisonings with some toxic compounds (drugs, organic solvents,
      etc.). Describes methods of preparing cadaveric material to analysis, examination
      of microsamples, and assessment of the results of analysis; examples of use of
      the method are offered.

PMID- 8296342
TI  - [Method of isolating carbamazepine from cadaveric material and its determination
      by fluorescent polarization immunoassay].
AB  - Optimal conditions for carbamazepine isolation from cadaveric liver have been
      determined. The authors recommend the material infusion with alcohol acidified
      with sulfuric acid to pH 1 three times for an hour. Conditions for measuring the
      isolated drug quantity have been developed. Fluorescent polarization
      immunoanalysis in the TDX system has been used for the first time. Carbamazepine
      detection limit for 50 g of the liver was found to be 2.5 x 10(-7) g.

PMID- 8296343
TI  - [Establishing the time of occurrence of mechanical trauma by the electrical
      conductivity parameters of skeletal muscles].
AB  - Presents the results of assessment of skeletal muscle electric conductivity
      parameters in various periods after an injury. Statistically reliable data were
      obtained indicating the possibility of establishing the period elapsed since
      infliction of a mechanical injury to skeletal muscles from parameters of active
      and reactive resistance at low and high frequencies. The fact that death occurred
      up to 72 h before virtually does not influence these parameters.

PMID- 8296345
TI  - [Psychogenic depressions in forensic psychiatric practice].
AB  - Analyzes the problems of diagnosis, classification, and assessment of psychogenic
      depression in forensic psychiatric practice. Clinical manifestations of such
      depressions are variable and numerous; the range of psychogenic depressions
      includes the borderline and psychotic forms each of which may be a separate
      entity or represent a stage in the development of a reactive depression.
      Distinguishing of these variants may be reasonable to assess the severity of a
      depressive disorder when deciding expert problems and for assessing the capacity
      of the subject exposed to expert evaluation to take advantage of his or her legal
      rights.

PMID- 8296344
TI  - [Device for calibration of gas-analytical apparatus in the analysis of
      organochlorine compounds].
AB  - Epoxy resin- and polymethylometacrylate-based polymeric matrices in the device
      for calibration of gas analytical equipment for analysis of organochlorine
      compounds are compared. Use of an organochlorine substance solution in
      polymethylmetacrylate matrix as a generator of these substances
      microconcentrations helps prolong the period of the device service to 15 months
      if the deviations of the concentrations from their mean value are up to 10%. An
      optimal composition of a polymethylmetacrylate-based matrix is offered.

PMID- 8296346
TI  - [Pathomorphosis of early organic brain lesions in forensic psychiatric practice].

PMID- 8296347
TI  - [Suicide by inflicting multiple penetrating wounds to the neck, chest and
      abdomen].

PMID- 8296348
TI  - [Anaphylactic shock to the intramuscular administration of milk].

PMID- 8296349
TI  - [Two cases of suicide by shots from a gas gun].

PMID- 8296350
TI  - ["Anatomy of the heart"].

PMID- 8296351
TI  - [Biochemical study of lipids in adrenals altered by putrefaction (the forensic
      medical diagnosis of stress)].
AB  - Biochemical method of lipid extraction with hexane permits the diagnosis of
      functional exhaustion of adrenals resultant from prolonged stress using both
      fresh material and that changed by putrefaction when histologic and histochemical
      methods of investigation are useless. These data may be used in examinations of
      putrescent corpses to assess thanatogenesis and establish the cause of death.

PMID- 8296352
TI  - [Topographic-anatomical basis for forensic medical assessment of central
      structures of the brain in craniocerebral trauma].
AB  - The paper is devoted to a method for topographic anatomic validation of a
      forensic medical evaluation of the status of the brain median structures in
      craniocerebral injury. Morphometric data are presented characterizing dislocation
      of the brain median structures in edema.

PMID- 8296353
TI  - Application of nucleic acid-based technologies to the diagnosis and detection of
      disease.

PMID- 8296354
TI  - Attitude towards family planning in Dharan, east Nepal: implications for the
      family planning programme.
AB  - A survey of the knowledge, attitude and practice of family planning was conducted
      in Dharan, Nepal. The town offers a full range of family planning services free
      of charge. There was a strong desire to limit family size; 52.5% of couples were
      currently using some modern method of family planning. Of the current users,
      62.3% had been sterilized, including 92.3% of those in the lowest socioeconomic
      group. Health risks and incompleteness of the family were the most common reasons
      for non-use of contraception, the latter reason reflecting ignorance of the
      temporary nature of some methods. There was a strong preference for male children
      and couples rarely used contraception until at least one so had been born. Even
      in this prosperous town where couples were highly motivated towards family
      planning and all methods were readily available, there was heavy reliance on
      sterilization. This is typical of Nepal and has largely been responsible for the
      failure of the family planning programme--as most couples choosing sterilization
      are in the older age group and have completed a relatively large family. If Nepal
      is to succeed in meeting its target of reducing the total fertility rate (i.e.,
      births per woman) from the current 5.8 to 4 by the year 2000 it will need not
      only to expand services but actively to promote temporary methods of
      contraception, particularly the more reliable longer acting reversible methods
      such as Depo-Provera, Norplant and intrauterine contraceptive devices.

PMID- 8296355
TI  - Sustained improvements in hygiene behaviour amongst village women in Lombok,
      Indonesia.
AB  - Fifty-seven mothers in Indonesia were involved in a face-to-face health education
      programme which encouraged hand-washing with soap. The intervention spanned 4
      months and comprised fortnightly visits by 2 community organizers, who supplied
      free soap. Two years after the intervention, 79% of mothers were still using hand
      soap, despite the fact that they now had to buy it themselves. The community
      seemed to be benefiting from a sustained reduction in diarrhoea episodes due to
      improved hygiene practices.

PMID- 8296356
TI  - Status of imported malaria in a control zone of the United Arab Emirates
      bordering an area of unstable malaria.
AB  - A concerted malaria eradication programme in the United Arab Emirates has reduced
      local transmission to only a very few small foci in the country. The Al Ain
      district is now a consolidation zone. However, transmission across the
      undemarcated border with Oman continues. Malaria imported by the large immigrant
      work force from major disease endemic areas remains a large burden. An added
      threat is the appearance of chloroquine-resistant Plasmodium falciparum
      principally from Sudan and Pakistan but increasingly amongst Omani cases seen in
      the hospitals and clinics in Al Ain. The implications of re-introduction of
      malaria and the establishment of chloroquine resistance, particularly for non
      immune residents and visitors, are emphasized.

PMID- 8296357
TI  - Bed nets for the prevention of malaria and anaemia in pregnancy.
AB  - A prospective comparison of the antimalarial efficacy of bed nets was conducted
      with 341 pregnant women living in a mesoendemic malarious area of the Thai
      Burmese border. Women in 3 adjacent study sites were allocated at random to
      receive either a single size permethrin-impregnated bed net (PIB), a non
      impregnated bed net (NIB), or to a control group who used either their own family
      size non-impregnated bed net (FNIB) or no net. In one study site, but not the
      other 2, PIB significantly reduced parasite densities and, together with FNIB,
      reduced the incidence of malaria in pregnancy from 56% to 33% (relative risk =
      1.67, confidence interval = 1.07-2.61, P = 0.03, allowing for parity). Anaemia
      proved a more sensitive marker of bed net antimalarial efficacy than parasite
      rates. The incidence of anaemia (haematocrit < 30%) at all study sites was
      significantly lower at delivery in the PIB (27%) and FNIB groups (21%) than in
      the NIB group (41%) or those using no net (56%). This suggests that a significant
      proportion of the malaria in pregnancy in this mesoendemic area was sub-patent.
      Both patent Plasmodium falciparum parasitaemia and anaemia were associated with a
      reduction in birth weight. Infant mortality was high (16%) and strongly
      associated with prematurity, low birth weight and maternal anaemia. PIB were well
      tolerated and had no apparent adverse effect on the pregnancy or infant
      development. Although the overall effect of bed nets on patent parasitaemia was
      marginal, they were associated with a significant reduction in maternal malaria
      associated anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296358
TI  - Leishmania braziliensis causing visceral leishmaniasis in a patient with human
      immunodeficiency virus infection, identified with the aid of the polymerase chain
      reaction.
AB  - This study describes a male patient with human immunodeficiency virus infection,
      grade IV-C (oropharyngeal moniliasis and Pneumocystis carinii pneumonia),
      associated with visceral involvement produced by Leishmania braziliensis which
      was identified by deoxyribonucleic acid hybridization after the polymerase chain
      reaction had been performed. The patient was treated with molgramostim in
      association with meglumine antimonate to enhance macrophage destruction of
      parasites.

PMID- 8296359
TI  - New foci of cutaneous leishmaniasis in central Kenya and the Rift Valley.
AB  - Active case detection and investigations of sandfly resting places in suspected
      transmission sites of cutaneous leishmaniasis in central Kenya and the Rift
      Valley resulted in the identification of several foci of the disease in Samburu,
      Isiolo, Laikipia, Nakuru and Nyandarua districts. The foci occurred in areas
      ranging from semi-arid lowlands at 400 m altitude to highland plateaux at 2500 m,
      including the floor of the Rift Valley, and were mostly inhabited by recently
      settled communities, nomads and migrant charcoal burners. Four species of
      Phlebotomus, 3 of the subgenus Larroussius (P. pedifer, P. aculeatus and P.
      guggisbergi) and one Paraphlebotomus (P. saevus) were collected from caves, rock
      crevices and tree hollows found in river valleys and in lava flows.

PMID- 8296360
TI  - Cutaneous leishmaniasis due to Leishmania tropica in Jordan.

PMID- 8296361
TI  - Estimation of hookworm intensity by anthelmintic expulsion in primary
      schoolchildren in south India.
AB  - A study was carried out between March 1990 and February 1991 to determine the
      prevalence and intensity of hookworm infection in 151 primary schoolchildren,
      aged 6-12 years, in Jalaripet, a slum area in South India predominantly inhabited
      by fishermen. Pre-treatment stool samples were processed by a modified formalin
      ethyl acetate sedimentation technique to determine ova counts. All children were
      treated with pyrantel pamoate and post-chemotherapy stools were collected over 48
      h to recover expelled worms. The overall prevalence of hookworm infection was 45%
      and the mean egg count was 192 eggs/g. The mean worm burden was 1.25 worms/child.
      The influence of host factors such as age and sex, environmental factors and
      behavioural factors on the intensity of egg output and worm burden was
      investigated.

PMID- 8296362
TI  - Epidemiology of Buruli ulcer in Amansie West district, Ghana.
AB  - This paper describes 90 cases of Buruli ulcer in Amansie West district, Ghana.
      49% were below 15 years of age while 20% were over 50 years. There was a
      significant difference in the age and sex composition, with more males among the
      younger age groups than females but the converse among adults. Seasonal variation
      is described, with peak incidence in September and October. Cases who had
      received bacillus Calmette-Guerin (BCG) vaccination had a shorter duration of the
      ulcer than those who were not vaccinated. No such association was found between
      BCG vaccination and the age of onset of the disease. There was no significant
      difference between cases and controls regarding their BCG vaccination status.
      There is an urgent need to regard Buruli ulcer in Ghana more seriously.

PMID- 8296363
TI  - The rapid manual ParaSight-F test. A new diagnostic tool for Plasmodium
      falciparum infection.
AB  - A rapid manual test for Plasmodium falciparum, the ParaSight-F test, has been
      used on a series of patients in a holoendemic malaria area of coastal Tanzania.
      The test, which is an antigen capture test detecting trophozoite-derived
      histidine rich protein-II, is simple to perform and provides a definitive answer
      in about 10 min. It requires no special equipment and is read using a single drop
      of blood. When compared with 272 thick blood films examined microscopically by 2
      observers and confirmed by the QBC malaria test, the ParaSight-F test had 88.9%
      sensitivity and 87.5% specificity. Detectable antigenaemia in a group of 40
      people declined following treatment with Fansidar and by 10 d after treatment all
      but 4 individuals were antigen free. The remaining 4, although clear of
      peripheral parasitaemia, remained antigenaemic for 14 d. The test shows great
      promise for rapid effective diagnosis of P. falciparum in clinics and village
      health centres where there is no facility for microscopy. Because of its accuracy
      and rapid action it may even obviate the need for microscopical examination of
      blood films to diagnose P. falciparum malaria.

PMID- 8296364
TI  - The importance of sensitive detection of malaria parasites in the human and
      insect hosts in epidemiological studies, as shown by the analysis of field
      samples from Guinea Bissau.
AB  - A method based on the polymerase chain reaction (PCR) for highly sensitive
      detection and identification of human malaria parasites was applied to blood and
      mosquito samples obtained from a village in Guinea Bissau. The prevalence of
      parasites in the human population was shown to be greatly underestimated by
      microscopical examination. In particular, a high incidence of Plasmodium malariae
      and P. ovale parasites was revealed only by the PCR assay. Preliminary evidence
      was obtained to show that the distribution of P. malariae infections within the
      village was non-random. This was supported by analysis of the parasite species
      infecting the mosquito vector. The implication of these results for the design
      and interpretation of epidemiological surveys is discussed.

PMID- 8296365
TI  - Diagnosis of Schistosoma haematobium infection: evaluation of ELISA using keyhole
      limpet haemocyanin or soluble egg antigen in comparison with detection of eggs or
      haematuria.
AB  - Keyhole limpet haemocyanin (KLH) was compared with Schistosoma haematobium
      soluble egg antigen (SEA) in the enzyme-linked immunosorbent assay (ELISA) for
      detection of S. haematobium infection, using 187 human sera collected from the S.
      haematobium endemic area of Pemba Island, Tanzania, and 30 normal sera from blood
      donors in Europe. There was a clear separation in terms of immunoglobulin (Ig) G
      and IgM titres between parasitologically positive patients and the blood donors,
      but titres of many parasitologically negative individuals in the endemic area
      were significantly high in comparison with the normal controls. Using as cut-off
      point the mean optical density +2 SD of sera from the blood donors to define
      ELISA positivity, and comparing the results with urine egg counts, the
      sensitivity of IgG-ELISA using KLH or SEA was high (91.11% and 95.56%,
      respectively) but the specificity was poor (43.30% and 31.90%, respectively.
      Similar results were obtained with IgM. When the 'gold standard' of haematuria
      and/or egg positivity as indicative of infection was used, the sensitivity of the
      ELISAs was similar but the specificity was increased to 59.25% and 44.44%,
      respectively. These results suggest that the patients with haematuria were
      probably infected with S. haematobium, which further supported the diagnostic
      value of haematuria detection for S. haematobium infection in endemic areas, and
      KLH was found to have a potential use in immunodiagnosis of S. haematobium
      infection in endemic areas. With both KLH and SEA antigens, the trend of
      reactivity in ELISA provided a correlate of the egg output (parasite burden) of
      infected patients.

PMID- 8296366
TI  - Community diagnosis of Bancroftian filariasis.
AB  - The objective of this study was to find the best tests for efficiently estimating
      the true prevalence of Bancroftian filariasis in endemic areas. The study
      population comprised 427 people over 10 years of age in an endemic village in
      Egypt. Four tests were evaluated; a standardized clinical examination, night
      blood examinations for microfilariae (50 microL thick films and 1 mL membrane
      filtration), and a test for circulating filarial antigen. 191 subjects (44.75%)
      had at least one positive test and were considered to have filariasis. The
      sensitivities of clinical examination, thick films, membrane filtration and
      antigen testing for filariasis were 16%, 50%, 64%, and 88%, respectively.
      Relative to membrane filtration of night blood, the filarial antigen test had a
      sensitivity of 97.5%, a positive predictive power of 71%, and a negative
      predictive power of 99%. None of the blood tests was a sensitive indicator of
      clinical filariasis; 69% of clinical cases were negative in all 3 blood tests and
      would have been missed if clinical examinations had not been done. Therefore, we
      recommend a combination of clinical examination and the filarial antigen test
      (with optional examination for microfilariae of those with positive antigen
      tests) for community diagnosis of Bancroftian filariasis in endemic areas.

PMID- 8296367
TI  - Overlap in the clinical features of pneumonia and malaria in African children.
AB  - Pneumonia and malaria are common causes of childhood morbidity and mortality in
      many developing countries and simple guidelines have been proposed to facilitate
      their diagnosis by relatively unskilled health workers. We have studied children
      in The Gambia attending out-patient and under-five clinics with clinically
      suspected pneumonia (cough or difficulty in breathing and a raised respiratory
      rate) during periods of high or low malaria transmission. During a period of high
      malaria transmission, 33% of these children had radiological evidence of
      pneumonia (with or without malaria parasitaemia) compared to 38% who had malaria
      parasitaemia, no radiological evidence of pneumonia and no other obvious cause of
      fever. Corresponding figures during a period of low malaria transmission were 48%
      and 6% respectively. The clinical overlap between pneumonia and malaria has
      important implications for case management strategies and evaluation of disease
      specific interventions in regions in which both pneumonia and malaria are
      prevalent.

PMID- 8296368
TI  - Glucose tolerance in pregnant patients with acute falciparum malaria.

PMID- 8296369
TI  - Two cases of cutaneous leishmaniasis in Malawi.
AB  - Leishmaniasis is rarely encountered in southern Africa. Two cases were diagnosed
      by histopathology in northern Malawi in one year. One was an 18 months old child
      with negative human immunodeficiency virus 1 (HIV-1) serology and widespread skin
      lesions; the other an HIV-1 positive adult with 2 skin lesions. The Leishmania
      species responsible could not be identified, but the infection may be more
      prevalent in this region than previously thought.

PMID- 8296370
TI  - Chlamydia trachomatis associated with chronic dysuria among patients with
      Schistosoma haematobium.
AB  - Eighty-seven Egyptians with Schistosoma haematobium infection (current or past)
      and chronic dysuria seen at the Theodor Bilharz Research Institute outpatient
      urology clinic in Imbaba, Cairo, Egypt were investigated for Chlamydia
      trachomatis infection. Direct fluorescent antibody tests (DFAT) showed 30
      urethral swabs (35%) and 40 urine sediments (46%) were positive for Chlamydia.
      Indirect fluorescent antibody testing showed 29 (34%) serum samples and 25 (29%)
      urethral smears were positive for Chlamydia. There was a highly significant
      association between patients with active Schistosoma infection and those with
      urine and urethral specimens positive for Chlamydia by DFAT (P < 0.01).

PMID- 8296371
TI  - First record of human infection with Echinostoma malayanum in India.

PMID- 8296372
TI  - Hydatid disease of the liver complicated by salmonellosis.

PMID- 8296373
TI  - Leprosy in an Italian tourist visiting the tropics.

PMID- 8296374
TI  - Clinical features associated with HIV-1 infection in adult patients diagnosed
      with tuberculosis in Djibouti, Horn of Africa.

PMID- 8296375
TI  - Renal ischaemia, transient glomerular leak and acute renal tubular damage in
      patients envenomed by Russell's vipers (Daboia russelii siamensis) in Myanmar.
AB  - Fifty-two patients who had been bitten by Russell's vipers in Myanmar developed
      acute renal failure (serum creatinine exceeding 1.3 mg/dL). Thirty-four of them
      (65%) became oliguric, but the other 18 (35%) maintained a urine output of more
      than 400 mL/24 h. In oliguric patients, gastrointestinal haemorrhages, renal
      angle tenderness and conjunctival oedema occurred more commonly, and peak serum
      creatinine, blood urea nitrogen and the fractional excretion of sodium were
      significantly higher (P < 0.01) than in non-oliguric patients, indicating a
      greater degree of renal damage. Urinary concentrations of beta 2 microglobulin
      and retinol binding protein were raised in most of the patients indicating
      failure of proximal tubular reabsorption of these proteins, while high urinary N
      acetyl glucosaminidase concentrations were consistent with renal tubular damage.
      Plasma concentrations of active renin were very high, suggesting that renal
      ischaemia, associated with activation of the renin-angiotensin system, was
      involved in the development of renal dysfunction.

PMID- 8296376
TI  - Neurotoxic envenoming by the Sri Lankan krait (Bungarus ceylonicus) complicated
      by traditional treatment and a reaction to antivenom.
AB  - A 30 year old woman bitten by a large Sri Lankan krait (Bungarus ceylonicus)
      developed progressive paralytic symptoms within one hour of the bite. After
      seeking traditional treatment her condition deteriorated and when she arrived at
      hospital 6 h after the bite she was drowsy, with bilateral ptosis and signs of
      aspiration pneumonia (a complication of traditional treatment). She developed an
      anaphylactic reaction after antivenom treatment and, despite treatment, had a
      cardio-respiratory arrest. She was resuscitated and mechanically ventilated, but
      remained deeply unconscious until her death 90 h after the bite. B. ceylonicus is
      endemic in Sri Lanka, is common in some areas, and could be mistaken for the
      common krait (B. caeruleus). It is doubtful whether any existing antivenom is
      effective against its venom.

PMID- 8296377
TI  - The efficacy of artemether in the treatment of Plasmodium falciparum malaria in
      Sudan.
AB  - The efficacy of artemether (a qinghaosu derivative) administered intramuscularly
      for the treatment of Plasmodium falciparum malaria was compared to quinine in an
      open randomized trial including 54 patients in eastern Sudan, where chloroquine
      resistance is common. The artemether treatment (5 d intramuscular regimen) was
      effective and the drug was well tolerated. All patients had cleared the
      parasitaemia and were free of symptoms 48 h after initiation of treatment. The
      parasite clearance time was comparable in patients receiving artemether and
      quinine. No side effect was reported by patients receiving artemether. No
      recrudescence was seen in 21 patients treated with artemether who completed 28 d
      follow-up. In the quinine group 3 of 18 patients had recrudescences, or possibly
      reinfections, on days 14, 21 and 28.

PMID- 8296378
TI  - Emergence of chloroquine-resistant Plasmodium vivax in Myanmar (Burma).

PMID- 8296379
TI  - Problems in the therapy of mixed malarial infections: a case of infection with
      Plasmodium falciparum and P. malariae treated with mefloquine and halofantrine.

PMID- 8296380
TI  - Albendazole is highly effective against cutaneous larva migrans but not against
      Giardia infection: results of an open pilot trial in travellers returning from
      the tropics.

PMID- 8296381
TI  - Use of dexamethasone in treatment of enteric fever complicated by cerebellar
      involvement.

PMID- 8296382
TI  - Thrombocytopenia complicating sodium stibogluconate therapy for cutaneous
      leishmaniasis.

PMID- 8296383
TI  - Gamma delta T cells in the peripheral blood of individuals from an area of
      holoendemic Plasmodium falciparum transmission.
AB  - gamma delta T cells bearing V gamma 9 T cell receptors from unexposed Caucasian
      donors make large responses to Plasmodium falciparum in vitro. This finding,
      together with observations of others showing high levels of V gamma 9+ T cells in
      the blood of infected non-immune individuals, led us to hypothesize that the
      response of these cells might contribute to the pathology of P. falciparum
      malaria. Acquisition of immunity to disease in people naturally exposed to
      infection may therefore be due in part to down-regulation or alteration of the
      function of gamma delta T cells. Supporting this view, and in contrast to
      infection in non-immune individuals, V gamma 9+ T cells are not elevated in
      peripheral blood of children or adults living in an endemic area despite constant
      exposure to P. falciparum. After in vitro stimulation with P. falciparum,
      however, the expansion of V gamma 9+ cells from the African donors is of similar
      magnitude to that observed for non-exposed Europeans. Thus, although these cells
      are not elevated in peripheral blood, they are still able to respond to P.
      falciparum antigens. In adult European donors the major gamma delta T cell
      population in peripheral blood is V gamma 9+ (approximately 70% of all gamma
      delta cells), whereas in the majority of adult Africans V delta 1+ V gamma 9- T
      cells predominated (approximately 70% of total gamma delta cells).

PMID- 8296384
TI  - Protective efficacy of high-titre measles vaccines administered from the age of
      five months: a community study in rural Senegal.
AB  - Using data on incidence and secondary attack rates, we examined the protective
      efficacy of high-titre Edmonston-Zagreb (EZ) and Schwarz (SW-HT) measles vaccines
      administered at 5 months. Control children were assigned to placebo at age 5
      months and standard Schwarz (SW-std) measles vaccine at 9-10 months of age. A
      large proportion of measles cases was verified serologically. Though high-titre
      vaccines seemed to be protective before 10 months of age, a significant reduction
      in disease could not be demonstrated due to low incidence of measles. After 10
      months of age, SW-std given at 10 months gave a vaccine efficacy of 100% and
      induced better protection than SW-HT (P = 0.030) and EZ-HT (P = 0.128)
      administered at 5 months. In studies of secondary attack rates in the compound,
      vaccine efficacy was 91% (75%-97%) for EZ-HT, 85% (40%-96%) for SW-HT, and 100%
      for SW-std. Attack rates were correlated with intensity of exposure (P = 0.0006),
      being much higher for children exposed in the same hut than for those living in
      the same compound but in a different household (relative risk = 3.36 [1.32
      8.57]). The attack rate was significantly lower among vaccinated than
      unvaccinated children with no detectable measles antibody (relative risk = 0.41
      [0.18-0.93]). In rural areas with a high coverage in the surrounding community, a
      single dose at 9-10 months may provide sufficient protection. Since high-titre
      vaccines have been associated with higher mortality than SW-std, further
      improvements in measles control before 9 months may require two-dose strategies
      with standard vaccines.

PMID- 8296385
TI  - RAPD (random amplified polymorphic DNA) analysis of Giardia DNA and correlation
      with isoenzyme data.
AB  - Fourteen Giardia duodenalis isolates were examined using the RAPD (random
      amplified polymorphic deoxyribonucleic acid) technique. Simple reproducible
      polymorphisms were generated using 3 different RAPD primers. The results
      generated by each primer were very similar and were significantly correlated with
      each other. These data were then compared to existing isoenzyme electrophoresis
      data on the same isolates. The RAPD data divided the isolates into 10 groupings
      or rapdemes while the isoenzyme data divided them into 10 similar zymodemes. Both
      methods grouped 4 isolates (BAH42, BAH44c9, BAH12c9 and BAH39c7), which comprised
      a phenotypically heterogeneous assemblage with respect to growth rate and
      metabolism, into similar groupings. The 2 methods were significantly correlated
      (P < 0.001). It will therefore be possible to use RAPD for the characterization
      of isolates of Giardia, and other parasites such as Cryptosporidium, which are
      refractory to cultivation in vitro.

PMID- 8296386
TI  - Characterization of Leishmania isolates from two AIDS patients originating from
      Valencia, Spain.

PMID- 8296387
TI  - Ciguatera fish poisoning.

PMID- 8296388
TI  - Chromaffin cells: roles for vesicle proteins and Ca2+ in hormone secretion and
      exocytosis.

PMID- 8296389
TI  - Adrenoceptor regulation in orthostatic hypotension during autonomic failure.

PMID- 8296390
TI  - Transcellular biosynthesis of leukotrienes and lipoxins via leukotriene A4
      transfer.

PMID- 8296391
TI  - Sites of action of carnitine and its derivatives on the cardiovascular system:
      interactions with membranes.
AB  - Carnitine plays an essential role in the regulation of long-chain fatty acid
      metabolism in skeletal and cardiac muscle, a process that is mediated by well
      characterized enzymatic mechanisms. Here, Irving Fritz and Edoardo Arrigoni
      Martelli review the evidence that carnitine and its O-acyl derivatives also
      influence membrane fluidity, ion channel functions, smooth muscle contractility,
      membrane stability and cardiac functions. The authors present the view that
      direct interactions of carnitine derivatives with cell membranes are independent
      of reactions catalysed by carnitine acyltransferases. They propose that the novel
      actions discussed are implicated in the mechanisms by which carnitine and its
      derivatives protect perfused hearts subjected to ischaemia or to oxidative
      stress, and help people suffering from certain types of myocardial ischaemia or
      peripheral arterial disease.

PMID- 8296392
TI  - Adenosine receptor subtypes.
AB  - The numerous and widespread effects of adenosine provide both an opportunity for
      the development of novel therapeutic agents acting via adenosine receptors and
      the challenge of achieving selectivity of action. The feasibility of achieving
      selectivity is enhanced if receptor subtypes can be identified. Biochemical,
      functional and receptor-cloning studies are beginning to provide convergent data
      supporting the existence of A1, A2A, A2B and A3 receptors. However, studies of
      the functional significance of these receptors in intact tissues both in vitro
      and in vivo have lagged behind the biochemical studies. In this article, Michael
      Collis and Susanna Hourani review the current status of adenosine receptor
      classification and propose that ligands with greater selectivity need to be
      evaluated in a wide range of functional preparations if the therapeutic potential
      of this area is to be realized.

PMID- 8296393
TI  - Synthetic low-molecular weight thrombin inhibitors: molecular design and
      pharmacological profile.
AB  - Thrombin is a multifunctional protein: in addition to its role in coagulation,
      thrombin has important biological effects on platelets, endothelial and smooth
      muscle cells, leukocytes, the heart and neurones. A detailed understanding of the
      structure of thrombin, of related serine proteases and of enzyme-inhibitor
      complexes has aided in the discovery of potent and selective new inhibitor
      molecules. Some of these novel thrombin inhibitors are active when administered
      orally and have shown remarkable efficacy as antithrombotic agents in animal
      models, offering a greater therapeutic potential than presently available drugs.
      This potential extends also to non-thrombotic indications where thrombin may be
      involved, namely inflammation, cancer and neurodegenerative diseases. The recent
      identification of specific thrombin receptors on different cells provides an
      alternative strategy for inhibiting thrombin's cellular actions, without
      necessarily compromising its role in haemostasis. In this review, Carlo
      Tapparelli and colleagues present a comprehensive update of these recent
      developments in the field of thrombin biology and pharmacology suggesting a new
      era of therapeutic drugs is on the horizon.

PMID- 8296394
TI  - Receptor subtypes or species homologues: relevance to drug discovery.
AB  - Cell surface receptors are targets for the pharmacological manipulation of
      physiological processes and thus represent a key direction for the development of
      selective therapeutic agents. Traditional pharmacological techniques, together
      with the development of synthetic ligands, have led to the identification of
      differences in receptor recognition properties and the proposal of multiple
      receptor subtypes. Molecular biological studies have confirmed the existence of
      receptor subtypes within a single species by demonstrating differences in
      receptor primary sequences. However, equivalent receptors between species also
      show differences in primary structure, albeit to a much lower degree. This review
      by Judith Hall and colleagues addresses the question of how differences in
      receptor primary structure between species relate to changes in pharmacology. The
      relevance of this to the choice of screens in the testing of potential
      therapeutic drugs is discussed.

PMID- 8296395
TI  - Orphan seven transmembrane domain receptors: reversing pharmacology.

PMID- 8296396
TI  - 5-HT and antidepressants: in vitro and in vivo release studies.

PMID- 8296397
TI  - Microdialysis studies with 5-HT reuptake inhibitors.

PMID- 8296398
TI  - Effects of 'rogue' points on non-linear fitting.
AB  - Computers make it possible to fit data directly to curves such as a hyperbola or
      the Hill equation (sometimes called logistic equation), and remove the
      requirement of previously used methods to convert the data so as they fit a
      straight line (as in Scatchard or Hill plots). There are good reasons for
      abandoning these older procedures, but what are the problems with the new ones?
      Errors in points at either end of straight line have more effect on the slope and
      intercept than errors in the middle range, but what is to be expected with a
      direct fit to curves? In this article, Dick Barlow describes the effects of
      errors at particular points ('rogue' points) on the results of the analysis for
      the fit of data by equally-weighted least-squares to: (1) a single line that may
      represent the results obtained in ligand-binding experiments or the relationship
      between dose and pharmacological response; (2) two dose-response curves that may
      represent the results obtained with a competitive antagonist and are used to
      calculate dose ratios; and (3) two dose-response curves in which the second curve
      is flattened that may represent the results obtained with an irreversible
      antagonist and are used to calculate the EC50 (apparent equilibrium constant) for
      the interaction between an agonist and a receptor. The method used involves
      making the repeated analysis of theoretical data and can be extended to other
      relations, including those describing pharmacokinetics.

PMID- 8296399
TI  - Modulation of intramitochondrial free Ca2+ concentration by antagonists of Na(+)
      Ca2+ exchange.
AB  - Evidence has accumulated in the past decade suggesting that Ca2+ acts as a second
      messenger not only in the cytosol of the heart to regulate contractility, but
      also within the mitochondria to regulate the rate of oxidative ATP synthesis.
      Just as elucidation of the second messenger pathways for Ca2+ in the cytosol has
      led to the development of pharmacological interventions that alter mechanical
      functioning of the heart, understanding the role of Ca2+ as a second messenger
      within the mitochondria and the mechanisms by which this organelle transports and
      regulates Ca2+ has exciting potential for developing pharmacological
      interventions that alter myocardial energy metabolism. In this article, David Cox
      and Mohammed Matlib discuss the potential consequences of pharmacologically
      increasing the intramitochondrial Ca2+ concentration on myocardial energy
      metabolism, and suggest some pathological conditions in which such an effect may
      be beneficial.

PMID- 8296400
TI  - Agonist regulation of cellular G protein levels and distribution: mechanisms and
      functional implications.
AB  - Exposure of cells to agonists of receptors linked to G proteins can result in
      downregulation of cellular levels or redistribution of G proteins from membranes
      to the cytosol. Agonist-induced reductions in G protein levels have been observed
      for members of each of the Gs, Gi and Gq families of G proteins, are likely to be
      dependent upon the level of receptor expression, and are generally restricted to
      the G protein(s) with which the receptor interacts. The mechanisms responsible,
      reviewed here by Graeme Milligan, vary with cell type and include both second
      messenger-dependent and -independent enhanced protein degradation. Agonist
      induced reduction in cellular G protein levels can provide one mechanism for the
      development of sustained heterologous desensitization.

PMID- 8296401
TI  - [Adverse effects of drugs and the liver].

PMID- 8296402
TI  - [Surgical treatment of benign recurrent goiter. Technique, complications and
      permanent sequelae].
AB  - Centre experience of reoperation for recurrent goitre in 82 patients during an 11
      year period is analysed. The lateralposterior approach is used as a standard
      surgical technique. Postoperative complications are prevalent only among patients
      previously operated on the thyroid gland twice or more, among patients with
      recurrent intrathoracic goitre, and among patients with large goitre relapse.
      Frequency of permanent unilateral vocal cord paresis amounts to 3.6%. There were
      no cases of bilateral recurrent nerve damage. The incidence of hypocalcemia
      requiring permanent treatment reaches 1.2%. Centre experience tends to reduce
      surgical complications rates with increasing specialized training. The surgical
      treatment for recurrent goitre ought to be radical to avoid further relapses. We
      recommend lobectomy in cases of unilateral recurrence and lobectomy of the
      dominant lobe with contralateral resection in case of bilateral relapse.

PMID- 8296403
TI  - [Positive effect of intermittent overpressure and underpressure (Vacusac) in
      intermittent claudication].
AB  - Twenty-two patients with intermittent claudication were included in a double
      blinded, randomized trial comparing the effects of 25 treatments with
      intermittent suction and pressure (Vacusac treatment) to 25 placebo applications
      given over a period of two months. Twelve patients participated in an open trial
      investigating the effects of the same treatment on adenosine diphosphate (ADP)
      induced platelet aggregation and fibrinolysis. Active treatment resulted in
      significant improvements in pain-free and maximal walking distances, whereas no
      changes could be found during placebo application. Active treatment caused
      significant increments in ADP-induced platelet aggregation, while the effects on
      fibrinolysis were uncertain. It is concluded that intermittent suction and
      pressure treatment offers a new approach for conservative treatment of
      intermittent claudication.

PMID- 8296404
TI  - [Immediate postoperative course and late results after inguinal herniotomy in
      children].
AB  - Three hundred consecutive children less than 18 years of age were treated for
      inguinal hernia by the same surgeon from 1970 to 1985. The surgical procedure was
      the same in all cases, namely ligation of the tunica vaginalis and extirpation of
      the hernial sac. Hernioplasty was not performed. Twenty patients were excluded.
      Seven patients had a recurrent hernia, i.e. a cumulative recurrence rate of 2.4
      per cent after a median follow up of 12 years (range 5-19). Five of seven (71%)
      recurred within five years after operation, while only two recurred from the
      fifth to the 15th year. We conclude that recurrence five years after operation is
      seldom and the recurrence rate in our work is acceptable compared with other
      publications.

PMID- 8296405
TI  - [Postoperative urinary retention requiring surgery].
AB  - Surgical procedures are often followed by postoperative urinary retention (PU).
      Sometimes PU is persistent, and prostate surgery, which might otherwise not have
      been required, is needed shortly after another operation. To find the frequency
      of this problem, we have retrospectively studied all cases of prostate surgery
      over a period of two years. Two hundred and fifty-eight operations were
      performed. Twenty were due to persistent PU after miscellaneous operations,
      mainly herniotomies and total hip arthroplasties. For men above 70 years old, the
      frequency of secondary prostate surgery was respectively 4% and 11% after these
      two operations. Eighty-five percent of the patients had symptoms of prostatism
      prior to the first operation. It is concluded that elderly men should be asked
      about voiding disorders before planned surgery, and these should be treated
      first.

PMID- 8296406
TI  - [Neonatal cancer in Denmark 1943-1985].
AB  - In order to describe the incidence, distribution and prognosis of neonatal
      cancer, 76 cases (44 boys, 32 girls) of cancer in the first 28 days of life were
      identified in the Danish Cancer Registry within the period 1943-85. All cases
      were re-evaluated and the International Classification of Disease for Oncology
      (ICD-O) code was applied. The incidence is calculated to 2.38 (1.88-2.98) cases
      per 100,000 births. The most common tumour was neuroblastoma (26%) followed by
      leukaemias (16%), soft tissue sarcomas (14%) and brain tumours (11%). The five
      year survival rate was 25% (15.1-39.0) with the highest survival rate among soft
      tissue sarcomas (55%) and neuroblastomas (25%) and the lowest among leukaemias
      and brain tumours (0). Eighteen per cent of the cases were incidental findings.
      Two cases of secondary malignancy were identified.

PMID- 8296407
TI  - [Sclerosing cholangitis and ulcerative colitis. Regional prevalence].
AB  - The aim of the study was to determine the prevalence of primary sclerosing
      cholangitis (PSC) in a regional population of patients with ulcerative colitis
      (UC). Three hundred and five patients with UC followed over a 12 year period were
      examined for elevations of serum alkaline phosphatase (> 280 U/l). Twenty four
      such patients were found. If no cause of these elevations were found by initial
      investigations, endoscopic retrograde cholangiography was performed in order to
      determine whether they had PSC. Eleven patients were found to have PSC (3.6%), of
      whom five had progressive disease, including two deaths from cholangio-carcinoma,
      during a six-year observation period. We found no certain relation between the
      extent, duration or activity of ulcerative colitis and the presence of PSC.
      Alkaline phosphatases were elevated up to 3.7 times the upper reference level,
      the aminotransferases were only found to be mildly elevated.

PMID- 8296408
TI  - [Adverse effects of subcutaneous administration of erythropoietin solution versus
      lyophilisate in patients receiving hemodialysis].
AB  - Twenty-two patients in haemodialysis were treated with erythropoietin
      subcutaneously in a double-blinded cross-over study with erythropoietin prepared
      either as a lyophilisate or an albumin-solution. The aim was to compare local
      reactions and pain. Both preparations were tolerated well. No major adverse
      reactions were seen. Erythropoietin albumin-solution was associated with
      significantly more burning pain than erythropoietin lyophilisate. Allergy does
      not seem to be involved. Albumin could be the irritative agent.

PMID- 8296410
TI  - [Vaccination of splenectomized children. Antibody response to Haemophilus
      influenzae type b conjugate vaccine].
AB  - Twenty splenectomized children and adolescents aged four to 18 years were
      immunized once with a Haemophilus influenzae type b (Hib) polysaccharide tetanus
      toxoid conjugate vaccine. Prior to vaccination, ten of 20 patients had
      anticapsular antibodies below what could be considered the minimum protective
      level in the splenectomized (0.6 microgram per ml), whereas all obtained high
      antibody levels after vaccination. In addition, one infant with congenital
      asplenia was vaccinated at two, four, and six months of age, and was shown to
      respond well after the second and third injections, obtaining serum antibody
      concentrations of 0.84 and 10.7 microgram per ml respectively. Because asplenic
      individuals have an increased risk of invasive Hib infection, these data suggest
      that vaccination of such individuals against Hib may be justified.

PMID- 8296409
TI  - [Hemostatic balance during treatment with the newest contraceptives].
AB  - Thirty-four healthy young women were allocated to 12 consecutive cycles of
      treatment with monophasic combinations of: 20 micrograms ethinyl estradiol and
      150 micrograms desogestrel (n = 15) or 30 micrograms ethinyl estradiol and 75
      micrograms gestodene (n = 19). In both groups plasma levels of fibrinogen and
      factor VII increased while the capacity of coagulation inhibition was affected by
      increased protein C and decreased protein S levels. Increased fibrinolytic
      capacity was indicated by elevated activity and reduced antigen levels of tissue
      plasminogen activator and reduced activity and concentration of tissue
      plasminogen activator inhibitor. The ratio between thrombin-antithrombin-III
      complexes and fibrin degradation products were unchanged signifying no effect of
      hormonal intake on the balance between thrombin formation and fibrin resolution.
      In conclusion, the dynamic balance between generation and resolution of fibrin
      was undisturbed during treatment with both hormonal compounds and our findings do
      not provide evidence for increased risk of thrombosis in normal women.

PMID- 8296411
TI  - [Collagenous colitis].
AB  - Collagenous colitis was first described in 1976 by Lindstrom as an unusual cause
      of persistent, watery diarrhea. He noted a large subepithelial band of collagen
      deposited in the rectum and the colon. Collagenous colitis occurs predominantly
      in females and is more frequent in the elderly. Radiographic examination of the
      colon is unremarkable, and the patients show no signs of malabsorption. The
      diagnosis requires biopsy specimens from the colon, as the disease is focal and
      less frequently affects the rectum. Biopsies taken only from the rectum cannot
      exclude the diagnosis. For the time being there is no consensus as to the
      treatment of the disease. We describe two patients with collagenous colitis
      successfully treated with prednisolone. The diagnostic importance of total
      colonoscopy with multiple biopsies in a normal-appearing colon in patients with
      unexplained chronic watery diarrhea is stressed.

PMID- 8296412
TI  - [Collagen and microscopic colitis].

PMID- 8296413
TI  - [Diphtheria toxin is carried into the cell by a growth factor].

PMID- 8296414
TI  - [Randomized oxytocin trial?].

PMID- 8296416
TI  - [High alcohol consumption--high surgical risk].

PMID- 8296415
TI  - [Drug therapy of cancer cachexia].

PMID- 8296417
TI  - [Postoperative morbidity among alcohol abusers].
AB  - Retrospective studies suggest increased postoperative morbidity among alcohol
      misusers. We have prospectively studied the risk associated with alcohol intake
      among patients undergoing surgery. We investigated 15 persons who required
      colorectal surgery and who were drinking at least five Danish drinks per day.
      These patients were matched for sex, nutrition, age, weight, cardio-pulmonary
      disease, diagnosis anesthesia, and surgery to 15 control persons who were
      consuming no more than two drinks daily. None of the patients showed signs of
      liver disease. The alcohol group developed more postoperative complications than
      controls (67 vs 20%, p < 0.05) and hospital stay was prolonged (20 vs 12 days, p
      < 0.05). Preoperatively, alcohol misusers had reduced left ventricular ejection
      fraction (54 vs 68%, p < 0.01). Delayed-type hypersensitivity responses were
      reduced in the alcohol group before (53 mm2 vs 78, p < 0.05) and after (18 mm2 vs
      55, p < 0.01) surgery. Alcohol misusers had significantly longer bleeding times.
      Surgical stress responses, as assessed by changes in plasma cortisol and
      catecholamines, were higher among alcohol misusers (p < 0.05). Postoperative
      morbidity was increased in alcohol misusers without signs of liver damage. The
      mechanisms may include subclinical cardiac insufficiency, immunosuppression, and
      decreased haemostatic function. Preoperative alcohol consumption may be a more
      important risk factor for postoperative morbidity than previously thought.

PMID- 8296418
TI  - [Alcohol-induced immunosuppression is reversible].
AB  - The aim of the study was to investigate to which degree and how fast cellular
      immunodepression may be reversed after cessation of alcohol intake. Delayed
      hypersensitivity was investigated in ten severe alcoholics and in seven moderate
      consumers. A group of eight previous drinkers was tested for comparison. The skin
      test responses were modest initially with a median area of response of 12 mm2 in
      the heavy alcoholics, and three mm2 in the moderate consumers. It improved
      significantly after two weeks of sobriety. The responses stabilized after eight
      to nine weeks at 63-74 mm2, corresponding to the response of 70 mm2 in the group
      of previous drinkers.

PMID- 8296419
TI  - [Postoperative morbidity after hysterectomy is related to alcohol consumption].
AB  - Postoperative morbidity after hysterectomy was studied prospectively in 229
      consecutive patients in our departments. The incidence of alcohol abuse (> or =
      60 gm of alcohol daily) and moderate drinking (between 25 and 60 gm of alcohol
      daily) was 6.5% for each. When compared with the moderate drinkers and the
      control group, the alcohol abusers developed significantly more complications
      (80% versus 27% and 80% versus 13% respectively). Preoperative history of alcohol
      consumption may define a group of patients at particular risk for increased
      postoperative morbidity.

PMID- 8296420
TI  - [Course after surgery of subdural hematoma in alcohol abusers].
AB  - The postoperative course and final outcome after evacuation of subdural haematoma
      are described in 106 male patients in relation to their alcohol consumption. One
      third of the patients were alcohol abusers, drinking at least 60 g of ethanol
      daily. Despite comparable head trauma, they had a significantly higher incidence
      of acute subdural haematomas and showed increased postoperative morbidity and
      mortality compared to the non-alcoholics. The postoperative hospitalization costs
      were initially higher and the final outcome was significantly worse for the
      alcohol abusers.

PMID- 8296421
TI  - [Treatment of carbon monoxide poisoning. Background and guidelines for oxygen
      therapy].
AB  - Treatment of carbon monoxide (CO) poisoning is still controversial. Standard
      treatment is pure oxygen either by means of a nasal catheter or oral-facial mask
      (normobaric oxygen treatment). Since 1960, hyperbaric oxygen (HBO) therapy has
      been applied in various centres, i.e. treatment in hyperbaric chambers with 100%
      O2 at 2-2.8 bars absolute pressure. Physically dissolved oxygen at this pressure
      is sufficient to maintain normal life functions at rest. HBO causes fast
      reoxygenation of tissues and accelerates the elimination of CO. In this paper,
      two cases treated with hyperbaric oxygen are reported. Aetiology, pathogenesis
      and possible sequelae of CO poisoning are reviewed. It is recommended, that all
      CO-victims, who have been or are unconscious at admission to the emergency ward,
      should be treated with HBO. In spite of there being comprehensive clinical
      literature concerning treatment of CO poisoning, there is still a great need for
      clinically controlled studies.

PMID- 8296422
TI  - [Morbidity, mortality and late sequelae in extremely premature infants born in
      the Hvidovre Hospital, 1985-1991].
AB  - In the period 1985 to 1991, 80 infants with gestational age below 28 completed
      weeks were born at Hvidovre Hospital, Copenhagen and transferred to the neonatal
      intensive care unit of the hospital. The incidence of extreme prematurity was 3.6
      0/00. Twenty-eight infants died during the neonatal period (35%) and nine infants
      died later in infancy (11.3%). Forty-three infants (54%) survived. Forty four
      percent of surviving infants had one or more sequelae related to their
      prematurity or neonatal complications, mainly blindness or reduced vision,
      cerebral palsy and mental retardation. Neither gender, mode of delivery or birth
      asphyxia were important for survival and sequels. Neonatal complications such as
      patent ductus arteriosus, septicaemia, necrotizing enterocolitis, pneumothorax
      and cerebral haemorrhages were significantly related to survival and sequelae.

PMID- 8296423
TI  - [Prevention of allergy in infants. A prospective study of 159 high-risk
      children].
AB  - A total of 105 infants at "high risk" for developing allergy born in 1988 were
      studied prospectively from birth to 18 months of age. The infants were
      recommended breastfeeding and/or hypoallergenic formula (Nutramigen or Profylac)
      combined with avoidance of solid foods the first six months of life. All mothers
      had unrestricted diet. Avoidance of daily exposure to tobacco smoking, furred
      pets and dust collecting materials in the bedroom was advised. This prevention
      group was compared to a control group consisting of 54 identically defined "high
      risk" infants born in 1985 in the same area. All the infants had either severe
      single atopic predisposition combined with cord blood IgE > or = 0.5 KU/l or
      biparental atopic predisposition. The control group had unrestricted diet and was
      not advised about environmental factors. The cumulative incidence of atopic
      symptoms was significantly lower at 18 months in the prevention group (32%)
      compared with the control group (74%) (p < 0.01), due to reduced incidence of
      recurrent wheezing (13% versus 37%; p < 0.01), atopic dermatitis (14% versus 31%;
      p < 0.01), vomiting/diarrhoea (5% versus 20%; p < 0.01) and infantile colic (9%
      versus 24%; p < 0.01). The cumulative incidence of food-allergy was significantly
      lower in the prevention group (6% versus 17%; p < 0.05). In both high-risk groups
      exposure to daily tobacco smoking increased the risk of recurrent wheezing
      significantly (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296424
TI  - [Knee arthroscopy under local anesthesia with or without anesthesiologic
      assistance. A cost-benefit analysis].
AB  - The benefit of anaesthesiological assistance during arthroscopy of the knee in
      local anaesthesia was evaluated in a cost-effectiveness analysis. One hundred
      consecutive patients had arthroscopy of the knee performed in local anaesthesia
      without anesthesiological assistance. In 15% of the cases the arthroscopy was
      insufficient because of pain reaction. Sixteen percent of the patients indicated
      that they would prefer general anaesthesia for a similar procedure in the future.
      The costs for arthroscopy of the knee in local anaesthesia without
      anaesthesiological assistance were calculated to Dkr. 2055. The amount includes
      costs for rearthroscopy in local anaesthesia with anaesthesiological assistance
      for 15% of the patients. Thirty-three patients had arthroscopy of the knee done
      in local anaesthesia with anaesthesiological assistance. General anaesthesia was
      needed for twelve percent of the patients. The cost for this procedure, including
      the costs of possible general anaesthesia were calculated to Dkr. 2458. Any
      significant difference in the sensation of pain during the arthroscopy could not
      be demonstrated between the two groups. Based on this study it is recommended
      that arthroscopy of the knee in local anaesthesia is planned without
      anaesthesiological assistance.

PMID- 8296425
TI  - [A comparison of 2 new rapid methods for determination of HbA1C concentration in
      patients with diabetes mellitus].
AB  - We have evaluated a new immunoturbidimetric assay (DCA 2000 HbA1c system, Bayer,
      Denmark) for determination of HbA1c. The aim of the study was to evaluate
      accuracy, precision and feasibility for the DCA 2000 method when employed in a
      diabetes centre by a technical assistant and at a general practitioner's by non
      lab staff. The results were compared with a high performance liquid
      chromatographic method (HPLC, AUTO A1C, Kyoto Daiichi Kagaku Co., Kyoto, Japan)
      which is the current laboratory method, and therefore used as reference. Assay
      time for the DCA 2000 method was nine minutes, while the HbA1c result was
      displayed within four minutes by HPLC. Blood samples were drawn after informed
      consent from 118 patients during a period of two months at the out-patient clinic
      of the Dept. of Paediatrics, Glostrup Hospital (n = 67) and at a general
      practitioner's (n = 51). Each sample was analyzed twice by each method on two
      consecutive days. In the HbA1c range from four to 14% (n = 67) the average within
      assay precision (SD) for the HPLC method was 0.13%, whilst it was 0.23% for the
      DCA 2000 method (p < 0.001). The within-assay precision was low and acceptable,
      and for both methods it was independent of the current HbA1c concentration. For
      the DCA method precision was almost similar (p > 0.07) when carried out by a
      technical assistant (SD: 0.20%) and by non lab staff (SD: 0.25%). Interbatch
      variations for HbA1c results investigated with two different batches of reagents
      within a month were SD 0.30% (HbA1c range: 4.9-5.9%, n = 30) and SD 0.44% (HbA1c
      range: 10.5-12.1%, n = 30) for these two preparations.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8296426
TI  - [Carbon monoxide poisoning due to lack of maintenance of a natural gas boiler].
AB  - Carbon monoxide causes one third of all poisoning deaths in Denmark, but is
      probably grossly underdiagnosed. We present a case where an elderly couple was
      admitted on several occasions to local hospitals with a variety of symptoms and
      signs; e.g. flu-like symptoms, generalized seizures, polycythaemia, chest pain,
      and ventricular tachycardia. The correct diagnosis, carbon monoxide poisoning,
      was made when the dog in the family was found dead; examination of the natural
      gas boiler revealed sooting, clogging of the flue, and a carbon monoxide
      concentration above 0.2 percent. The natural gas boiler had not been checked
      after installation five years earlier. Natural gas installations are becoming
      still more prevalent in Danish homes, but present regulations regarding the
      installations are apparently not yet able to prevent new incidents of carbon
      monoxide poisoning.

PMID- 8296427
TI  - [rhG-CSF treatment in cyclic neutropenia. Continuous versus intermittent rhG-CSF
      treatment in cyclic neutropenia].
AB  - Cyclic neutropenia is a stem-cell disorder characterized by regular 21-day cyclic
      fluctuations in the number of neutrophils in the blood and bone marrow. The
      neutropenic periods may be complicated by fever, stomatitis and severe
      infections. In this case report only daily continuous and later intermittent
      treatment with recombinant human granulocyte colony-stimulating factor (two
      micrograms/kg) administered subcutaneously effectively prevented recurrent
      infections.

PMID- 8296428
TI  - [Chloroform exposure: risk assessment in others than swimmers].

PMID- 8296429
TI  - [Cholesterol lowering drugs].

PMID- 8296430
TI  - [Treatment of priapism: "black pudding" or no black pudding].

PMID- 8296431
TI  - [Purulent meningitis and mortality].

PMID- 8296432
TI  - An improved method for the scintigraphic detection of acute bone damage to the
      equine pelvis by probe point counting.
AB  - A fracture of the pelvis in a horse can be detected scintigraphically by probe
      point counting. However, the pelvis is covered by a large and variable muscle
      mass, and is close to the urinary bladder, both of which can introduce errors.
      This paper describes an improved technique which uses a larger set of sampling
      points and analyses the data with a small computer to construct a three
      dimensional graph of the gamma-ray output across the pelvis, thus helping to
      improve the interpretation of the data. The scintigraphic plot from a normal
      horse, three cases of fracture (confirmed by radiography, ultrasound imaging or
      post mortem examination) and examples of the artefacts produced by isotope in the
      bladder and by marked muscle wasting are presented.

PMID- 8296433
TI  - The economics of culling dairy cows with clinical mastitis.
AB  - Culling dairy cows with clinical mastitis reduces the incidence of the disease in
      dairy herds, but the costs of such action, in terms of reduced milk production
      and increased replacement costs, are generally thought to outweigh the benefits.
      To test this hypothesis a stochastic dynamic programming model was developed to
      establish the economically optimum time of replacement for dairy cows subject to
      variable levels of clinical mastitis infection, using average United Kingdom
      production and price parameters. The optimal stage at which to replace a dairy
      cow was found to be sensitive to changes in mastitis incidence and in critical
      price parameters within the bounds of commercial experience. This result
      indicates that an objective culling policy based on clinical mastitis records in
      addition to milk production potential may be economically viable.

PMID- 8296434
TI  - Diagnosis and treatment of metabolic acidosis in calves: a field study.
AB  - The history and results of a clinical examination were recorded for 32 spring
      born suckler calves which were hospitalised for intravenous fluid therapy. Blood
      samples were taken before treatment, during treatment and before discharge and
      analysed for colostral status, total carbon dioxide as an indication of acid-base
      status, and haematocrit. All the calves were given intravenously 5 to 10 litres
      of electrolyte solution containing 144 mmol/litre sodium, 4 mmol/litre potassium,
      113 mmol/litre chloride and 35 mmol/litre bicarbonate, supplemented, in 24
      calves, with up to 450 ml of 1M sodium bicarbonate. Nearly all the calves were
      recumbent but less than half were dehydrated on admission. The signs of
      dehydration were well correlated with each other and with the haematocrit.
      Neither the history nor the clinical signs were useful predictors of acidosis.
      There was no relationship between the severity of acidosis and the degree of
      dehydration. Acidosis was more prevalent in older calves (P < 0.01). For the
      severely acidotic calves, supplementary intravenous fluid with sodium bicarbonate
      significantly (P < 0.05) improved the total blood carbon dioxide at discharge.
      All 32 calves recovered. It is possible to treat acidotic calves with intravenous
      fluid therapy effectively, economically and according to their individual needs.
      The Harleco apparatus is a simple, useful, cost-effective adjunct to the
      diagnosis and treatment of this life-threatening condition.

PMID- 8296435
TI  - Mycobacterium avium infection in a pygmy goat.

PMID- 8296436
TI  - 'Broken backs' in koi carp (Cyprinus carpio) following lightning strike.

PMID- 8296437
TI  - Possible link between cattle and E coli O157 infection in a human.

PMID- 8296438
TI  - Equine pharmaceutical products.

PMID- 8296439
TI  - FeLV vaccination.

PMID- 8296440
TI  - Use of monensin sodium in sheep feeds.

PMID- 8296441
TI  - Growth of lactobacilli, Staphylococcus aureus and Escherichia coli in normal and
      mastitic milk and whey.
AB  - The growth of three lactobacilli (Lactobacillus acidophilus, L. bulgaricus and L.
      casei), Staphylococcus aureus and Escherichia coli was followed in normal and
      mastitic milk and whey using the standard plate count method. L. acidophilus, L.
      bulgaricus 6032 and L. casei 6028 grew well in normal milk, but had decreased
      growth in mastitic milk if not pre-adapted in mastitic whey. S. aureus 26003 and
      E. coli 44102 showed enhanced growth in mastitic milk as compared with their
      growth in normal milk. These mastitis pathogens grew faster than the lactobacilli
      in both the normal milk and the mastitic milk. Among the lactobacilli, L.
      acidophilus and L. bulgaricus grew faster than L. casei in both types of milk
      samples. All the bacteria tested grew well in the normal and mastitic whey
      samples. However, they seemed to have enhanced growth in mastitic whey with the
      exception of L. casei. Pre-adaptation of the bacteria in mastitic whey in
      subculture markedly improved the growth of both pathogenic and non-pathogenic
      bacteria in mastitic milk. All the bacteria showed decreased replication in
      mastitic milk as compared with mastitic whey.

PMID- 8296442
TI  - Antigen capture ELISA using a monoclonal antibody for the detection of Mycoplasma
      bovis in milk.
AB  - An enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody (mAb)
      was developed to detect Mycoplasma (M.) bovis in milk samples from cattle. With
      this procedure, 1 x 10(5) colony forming units per ml (cfu/ml) milk were
      routinely detectable. No cross-reactions to other bovine mycoplasma species were
      observed. Both the sensitivity of 80.6% and the specificity of 94.9% are
      sufficient for its use in diagnosis of clinical mastitis. The sensitivity could
      be increased by 10% after introduction of 48-hour pre-incubation of samples. This
      allowed recognition of cows shedding M. bovis amounts of 10(3) cfu/ml in their
      milk, which is typical for subclinical cases. Screening of milk samples by means
      of this antigen capture ELISA has advantages over culture methods in terms of
      speed and potential to monitor large herds, thereby permitting early culling of
      infected animals to reduce transmission of the pathogen to non-infected animals.

PMID- 8296443
TI  - Passive protection against bovine rotavirus-induced diarrhea in murine model by
      specific immunoglobulins from chicken egg yolk.
AB  - Chicken egg yolk immunoglobulins (yIg) specific against bovine rotavirus (BRV)
      serotypes 6 (strain Shimane) and 10 (strain KK-3) were used for oral passive
      immunization of suckling mice against experimental BRV challenge. The protective
      capacity of the antibody preparation was tested using different concentrations of
      yIg against a challenge dose of 10(7.5) TCID50 for Shimane and 10(7.0) TCID50 for
      KK-3 strain. There was a significant homotypic (P < 0.05) and heterotypic (P <
      0.01) protection using 160 anti-Shimane or 160 anti-KK-3 neutralizing antibody
      titer (NAT) compared to control mice given yIg derived from eggs of mock
      immunized (control) hens. The titer of infectious BRV recovered from intestinal
      tissue or luminal chyme decreased with increasing homotypic yIg NAT. A decrease
      in degree and duration of BRV antigen localization in the villus epithelial
      lining was observed in mice treated with homotypic yIg at optimum dose for
      prevention of diarrhea. The NAT in sera of challenged mice increased with
      decreasing NAT in the yIg given before challenge suggesting that protection was
      dose-dependent. The present findings indicate that a passive protection could be
      achieved by the use of yIg against BRV-induced diarrhea in this murine model.

PMID- 8296444
TI  - The effect of EHV-1 infection upon circulating leucocyte populations in the
      natural equine host.
AB  - It has been suggested that EHV-1 infection may perturb immune responsiveness in
      the natural equine host. The mechanism underlying this phenomenon is not clear,
      but disturbances of circulating leucocyte populations could contribute. In order
      to objectively assess the nature of the haematological changes provoked by EHV-1
      infection, two groups of conventionally-maintained Welsh mountain ponies were
      challenge-infected intra-nasally with the Ab4 isolate of EHV-1. These groups were
      controlled by similarly-sized groups of non-infected ponies. All data generated
      was subjected to rigorous statistical analysis. Whole leucocyte count, neutrophil
      count, lymphocyte count, pan T cell count (RVC1 + cells-putative CD5 homologue),
      T cell subset count (RVC3 + cell-putative CD8 homologue), RVC2 + cells
      (putatively class II MHC+) and B cell count were recorded in experimental and
      control subjects at frequent intervals post-infection via flow cytometry. The
      principal abnormalities post-infection were T cell lymphopaenia, neutropaenia and
      the appearance of blastic cells of undetermined lineage. This study underlined
      the variability of EHV-1 infection in the natural, outbred equine host.

PMID- 8296445
TI  - Studies on manifestations of canine distemper virus infection in an urban dog
      population.
AB  - An upsurge of canine distemper was recognized at the beginning of 1991 in the
      urban dog population of the Copenhagen area. The outbreak had the characteristics
      of a virulent morbillivirus introduction in a partly immune population, where the
      disease primarily was manifested in young individuals. Testing of single serum
      samples for the presence of canine distemper virus (CDV) IgM antibodies using an
      IgM ELISA confirmed current and recent CDV infections in an urban dog population,
      where the use of attenuated CDV vaccines was widespread. In 49 out of 66 sera
      from clinical cases suspected of canine distemper we detected CDV IgM antibodies,
      as compared to the detection of viral antigen by indirect immunofluorescence in
      27 of 65 specimens of conjunctival cells. The antigenic make-up of isolates from
      acute and subacute clinical cases was investigated with a panel of 51 monoclonal
      antibodies directed against CDV and the related phocine distemper virus. The
      isolates exhibited an homogeneous reaction pattern and shared overall antigenic
      characteristics of the CDV prototype. The majority of cases were diagnosed among
      unvaccinated dogs and individuals with unknown or obscure vaccination record.
      However, severe clinical cases were also diagnosed in vaccinated individuals.

PMID- 8296447
TI  - The isolation of sucrose-fermenting Salmonella mbandaka.
AB  - During media trials to evaluate the use of Brilliant Green Agar for the primary
      recognition of Salmonella, strains presenting fermentation reactions were
      observed. All fermenting strains (84 out of 145) belonged to the serotype
      Salmonella mbandaka (58%), and the activity was expressed on three batches of
      Brilliant Green Agar and one of Xylose-Lysine Desoxycholate Agar. It was
      established using individual lactose and sucrose broth that the reaction in these
      media was due to sucrose fermentation. The most frequently isolated Salmonella in
      this laboratory during 1990 was S. mbandaka (61%) i.e. 65 of the 106 isolates
      during this period. Primary differentiation of Salmonella from other members of
      the family Enterobacteriaceae on media incorporating sucrose would have resulted
      in 36% of Salmonella isolates not being recognised. BGA and XLD agar therefore
      would not be suitable for primary isolation of Salmonella from clinical material
      with such a high percentage of the major isolate, S. mbandaka, having the ability
      to ferment sucrose.

PMID- 8296446
TI  - Enzymatic activities of Dermatophilus congolensis measured by API ZYM.
AB  - API ZYM kit was used to test enzymatic activities on eighteen strains of
      Dermatophilus congolensis. All strains produced lipase and acid phosphatase,
      which act on lipids, and leucine arylamidase which act on proteins. Another 10
      exoenzymes were present in at least one of the strains.

PMID- 8296448
TI  - Rotavirus excretion in naturally infected pigs with and without diarrhoea.
AB  - Seven hundred and fifty faecal samples from piglets ranging from 1 to 60 days old
      were studied for the presence of group A rotavirus by polyacrylamide gel
      electrophoresis (PAGE) and by enzyme immunoassay (EIA). From 451 diarrhoeic pigs,
      117 (25.94%) were positive for rotavirus and only 45 (15.05%) of 299 pigs without
      diarrhoea excreted the virus (P < 0.005). When these animals were separated into
      four age groups with regard to the presence or absence of diarrhoea, it was
      observed that the excretion of rotavirus was associated with diarrhoea in
      piglets, both before and after weaning.

PMID- 8296449
TI  - Antigen profiles of Anaplasma ovis and A. mesaeterum and cross infection trials
      with them and A. marginale.
AB  - Antigen profiles of Anaplasma ovis and A. mesaeterum were analysed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting, and cross
      infection trials were performed by A. ovis challenge to A. mesaeterum- or A.
      marginale-inoculated goats and A. marginale challenge to an A. ovis-inoculated
      calf. Antigen analysis showed unique and common proteins of A. ovis and A.
      mesaeterum and identified a major 38 kDa protein to be a dominant immunogen
      bearing two epitopes common to Anaplasma species. An epitope specific to A. ovis
      and A. marginale, absent from A. mesaeterum, was recognised on the major protein
      of A. ovis. Pre-inoculation of goats with A. mesaeterum induced continuous
      antibody response with low parasitemia and partial protection against A. ovis
      challenge, as demonstrated by lower peak parasitemia and normal body temperature
      compared with values for goats inoculated with A. ovis alone. Pre-inoculation of
      goats with A. marginale and a calf with A. ovis induced weak or no antibody
      response without parasitemia, and was of no effect for preventing anaplasmosis by
      heterologous challenge. These results suggest that the development of parasitemia
      is essential for inducing continuous antibody by which cross protection would be
      possible.

PMID- 8296450
TI  - Molecular analysis of a cryptic plasmid isolated from avian strains of
      Pasteurella multocida.
AB  - Twelve small plasmids isolated from avian strains of Pasteurella multocida were
      examined by restriction enzyme mapping, cross-hybridization, and minicell
      analysis. These plasmids contained sites for several commonly used restriction
      enzymes and ranged in size from 3.4 to 3.8 kilobases. Restriction enzyme maps of
      the 12 plasmids were similar and divided the plasmids into 3 families, designated
      pFS1, pFS2, and pFS4. Restriction fragments of pFS1 DNA isolated from strain X-73
      were used to probe AvaI/HindIII/EcoRV digests of pFS2 and pFS4 DNA. The results
      of these hybridization experiments demonstrated that the plasmids found in all
      three families shared extensive regions of homology and may have originated from
      a common ancestor. Escherichia coli minicells containing recombinant plasmid
      constructs bearing fragments of pFS1 expressed two pFS1-specific peptides, 12.5
      and 28 kilodaltons in size, suggesting that some P. multocida plasmid-encoded
      proteins can be expressed in E. coli. These results indicate that pFS may be
      useful as a genetic tool for moving DNA into and out of P. multocida, since it is
      small, contains common restriction sites, and encodes at least two genes that are
      recognized and expressed in E. coli.

PMID- 8296451
TI  - Some cultural characteristics of Branhamella ovis isolated from the conjunctival
      sac of sheep.
AB  - The colonial morphology and other cultural characteristics of Branhamella ovis
      were studied. The current investigation showed that colonies could be designated
      R (rough) and S (smooth) dependent on their appearance on agar. The colonial
      variants were apparently stable and each produced distinct types of pitting when
      grown on agar. A CAMP-like reaction was also shown to be a characteristic of B.
      ovis.

PMID- 8296452
TI  - Identification and partial characterization of a group of weakly beta-hemolytic
      intestinal spirochetes of swine distinct from Serpulina innocens isolate B256.
AB  - Comparative analyses of a group of 16 weakly beta-hemolytic spirochetes isolated
      from feces and mucosal scrapings of intestines of swine in the midwestern United
      States, and eastern Canada revealed the existence of a phenotypically and
      genotypically related group of 7 isolates. Although isolates in this group
      differed from all known reference isolates of intestinal spirochetes of swine,
      partial similarity was detected with S. joneseae isolate 16, a newly identified
      weakly beta-hemolytic intestinal spirochete of human beings. In addition to
      producing weak beta-hemolysis on blood agar plates, S. innocens isolates B256 and
      4/71, S. joneseae isolate 16, and the 16 field isolates lacked the characteristic
      ring phenomenon described for Serpulina hyodysenteriae, an enteropathogenic
      spirochete of swine. All but one of the field isolates of weakly beta-hemolytic
      intestinal spirochetes gave negative results for indole production. The same
      isolates yielded variable results for alpha-galactosidase production. By
      transmission electron microscopic examination of negatively-stained cross
      sections of spirochetes, the isolates segregated into groups containing either 4
      to 7 or 9 to 16 profiles of axial filaments per cell cross-section. Analyses of
      genomic DNA of selected isolates using whole-genome cross-hybridization revealed
      a single genetic type consisting of 7 field isolates of weakly beta-hemolytic
      intestinal spirochetes. The 7 field isolates were distinct from the reference
      isolates S. innocens isolates B256 and 4/71, S. hyodysenteriae isolates B78 and
      B204, and Treponema succinifaciens isolate 6091 based on the number of axial
      filaments per cell cross-section and lack of cross-hybridization signal. S.
      joneseae isolate 16, had the same number of axial filaments per cell cross
      section and produced a weak hybridization signal with a representative isolate of
      the 7 weakly beta-hemolytic field isolates from swine. This report suggests the
      existence of a widely distributed group of closely related weakly beta-hemolytic
      intestinal spirochetes of swine with genotypic characteristics distinct from S.
      innocens isolate B256.

PMID- 8296453
TI  - Comparison of type I and type II Chlamydia psittaci strains infecting koalas
      (Phascolarctos cinereus).
AB  - The native Australian marsupial Phascolarctos cinereus, otherwise known as the
      koala, is prone to infection by the obligate intracellular parasite Chlamydia
      psittaci, which causes ocular 'pink eye' and urogenital 'dirty tail' diseases.
      Several chlamydial DNA probes to both chromosomal and plasmid sequences were used
      to type by Southern blot analysis 51 samples taken from wild and captive koalas
      from habitats on the eastern seaboard of Australia as far apart as Queensland and
      Victoria. Two types of C. psittaci were observed and called types I and II. Type
      II was found more frequently than type I and occurred in both ocular and
      urogenital samples, while type I showed a strong but not absolute preference for
      ocular sites. Cross-hybridization analyses indicated that type I and type II had
      about 10% DNA sequence identity to each other. DNA analyses showed that type II
      was very closely related to some ovine and bovine chlamydiae but type I could not
      be related to any other C. psittaci strain available. Light and electron
      microscopic analyses of infected BGM monolayers revealed that the two strains
      were similar in morphological characteristics. The type I strain was considerably
      more infectious than the type II strain in BGM cells and in the yolk sacs of
      embryonated eggs. A PCR based assay detected both type I and type II koala
      chlamydiae in samples that had been negative by Southern blot and tissue culture
      and provided the first evidence that both types can occur simultaneously at the
      one site of infection.

PMID- 8296454
TI  - The importance of secreted virulence factors in Actinobacillus pleuropneumoniae
      bacterin preparation: a comparison.
AB  - Current bacterins provide only partial protection against morbidity and mortality
      in swine following infection by Actinobacillus pleuropneumoniae. We compared the
      efficacy of a cell-free concentrate from mid-log phase growth cultures of
      Actinobacillus pleuropneumoniae (APP) serotype 1 to four commercial bacterins.
      This cell-free preparation contained carbohydrate, endotoxin, and protein, and
      had hemolytic and cytotoxic activity. Sodium dodecyl-sulfate polyacrylamide gel
      electrophoresis analysis indicated the presence of one major 110,000-molecular
      weight protein. This protein band also stained by the periodic acid Schiff
      method, indicating the presence of carbohydrate. Cell-free concentrates of APP
      serotypes 5 and 7 had identical profiles following electrophoresis and staining
      with either Coomassie blue for protein or Schiff reagent for carbohydrate.
      Lipopolysaccharide profiles for the cell-free concentrates of serotypes 1 and 5
      were semi-rough while the LPS profile for serotype 7 was smooth. Five A.
      pleuropneumoniae-free SPF pigs per group were vaccinated on days 0 and 21 with
      cell-free concentrate of serotype 1 plus adjuvant, or one of four commercial
      bacterins according to the manufacturer's directions. Control pigs were
      vaccinated with PBS mixed with adjuvant. All pigs were challenged intranasally on
      day 35 with serotype 1 and necropsied on day 50. Protection was greatest in the
      cell-free concentrate group, as compared with all other groups, in that no deaths
      occurred, clinical scores were less severe, and percent lung affected was
      significantly reduced (P < 0.05). In addition, whole-cell ELISA titers were
      significantly increased (P < 0.05) postvaccination in the cell-free concentrate
      group, and postvaccination and postchallenge sera neutralized the hemolytic
      activity of the cell-free concentrate from serotypes 1 and 5 (P < 0.05), as
      compared with all other groups. No serum neutralization to the hemolysin of
      serotype 7 was observed. Immunoblot analysis using antisera derived from
      gnotobiotic pigs indicated that the cell-free vaccine generated a response that
      was identical to the response observed following live challenge. Similar, but not
      identical, responses were observed when antisera generated against the bacterins
      was used. This study indicates that an acellular vaccine containing multiple
      virulence factors can provide complete protection from mortality and
      significantly reduced morbidity to homologous challenge.

PMID- 8296455
TI  - Neural bases of visual deficits during aging.
AB  - Visual abilities decline during normal (non-pathological) aging. Many of these
      visual declines cannot be attributed to optical changes and must therefore be due
      to changes in the retina or central visual pathways. These include declines in
      visual acuity and spatial contrast sensitivity (especially under low luminance
      levels), suprathreshold contrast vision and contrast gain, temporal-frequency
      contrast sensitivity and resolution, spatial-temporal interactions, hyperacuity,
      binocular processing, and sensitivity to motion. Certain aspects of these vision
      deficits and comparisons with neurophysiological and lesion-behavior studies in
      monkeys suggest hypotheses about the nature and location (e.g. magnocellular vs
      parvocellular pathways, specific visual structures, and so on) of the neural
      deficits. Despite the well-documented psychophysical deficits, available
      anatomical studies in humans and monkeys suggest that aging has only relatively
      minor effects on the retino-geniculo-striate pathway. Retinal photoreceptor
      losses are relatively restricted to rods, and there is compensation among the
      remaining rods for those that are lost. Although some retinal ganglion cells
      appear to be lost, the loss is small relative to individual-to-individual
      variability. In addition, there appear to be no massive cell losses in the LGN or
      striate cortex. Physiological results in the monkey LGN suggest that the
      functional properties of LGN neurons, and therefore their retinal inputs, are not
      significantly affected by aging. Retinal pattern-evoked ERG studies in humans
      likewise suggest that the physiological properties of the retina are little
      affected by aging. Comparisons between pattern-evoked ERG and cortical evoked
      potentials in the same individuals suggest that some neural change occurs between
      the retina and striate cortex, but the location and nature of this change is not
      known. Thus, we are far from being able to answer the question, What are the
      neural bases of visual deficits during aging? There are several possible reasons
      for this: (1) The neurobiological methods that have been brought to bear on the
      question have been fairly limited. (2) Investigations of neural changes may not
      have been guided sufficiently by what is known about the psychophysical changes
      that occur with aging. (3) Existing studies may not have examined the correct
      locations in the visual system. (4) There is large individual-to-individual
      variability in the effects of aging and, with the small samples of individuals
      that typically are available in neural studies of aging, the variability could
      obscure detection of aging-related changes. Suggestions are offered for ways in
      which future research can solve these problems.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8296456
TI  - Localization and modulatory actions of zinc in vertebrate retina.
AB  - Zinc ions are colocalized with glutamatergic synaptic vesicles in vertebrate
      photoreceptors and may act as a diffusible molecular switch regulating
      neurotransmitter signaling at two distinct sites in the outer retina. In the
      dark, extracellular zinc acts presynaptically at rods and cones to minimize the
      depletion of tonically released glutamate, and selectively reduces GABA-mediated
      depolarization in horizontal cells, accelerating the response kinetics of the
      second-order cells. The discovery of zinc ions in photoreceptors provides a
      mechanism for gain control, kinetics modulation, and the balance of rod vs cone
      output at the first synapse in the visual system.

PMID- 8296457
TI  - Immunocytochemical localization of GABA and glycine in amacrine and displaced
      amacrine cells of macaque monkey retina.
AB  - Recent studies have varied widely in the percentages of GABA- and glycine
      immunoreactive (GABA+, GLY+) amacrines reported for primate retina. We compared
      the distributions of GABA+ and GLY+ amacrines and displaced amacrines at seven
      locations along the horizontal meridian of macaque retina using postembedding
      immunogold labeling with silver intensification. The percentage of GABA+ amacrine
      profiles was higher in central retina (50-55%) than peripheral retina (30-40%),
      whereas the percentage of GLY+ amacrine profiles did not vary much with
      eccentricity (52-57%). GABA and glycine were colocalized in 5-20% of amacrines,
      depending on the eccentricity, whereas 5-30% of amacrines were not immunoreactive
      for either neurotransmitter. GABA+ amacrines were slightly larger than GLY+
      amacrines or Muller cells. In the ganglion cell layer, 5-20% of neurons were
      labeled for either GABA or glycine and were identified as displaced amacrines. Of
      these, 53% were GABA+ only, 11% were GLY+ only, and 37% were double-labeled. A
      few large, very lightly labeled GABA+ cells were identified as ganglion cells.
      Other features that varied with eccentricity included the linear density of GABA+
      and GLY+ amacrines, and the ratio of amacrines to Muller cells.

PMID- 8296458
TI  - GABA-immunoreactive profiles provide synaptic input to the soma, axon hillock,
      and axon initial segment of ganglion cells in primate retina.
AB  - GABA-immunoreactive displaced amacrines were previously shown to make synapses
      onto neuronal profiles in the ganglion cell layer (GCL) of macaque monkey retina
      [Koontz, Hendrickson and Ryan (1989) Visual Neuroscience, 2, 19-25]. These
      postsynaptic elements have been investigated further using postembedding
      immunogold methods for electron microscopy. This paper provides ultrastructural
      evidence that GABA-immunoreactive profiles are presynaptic to the ganglion cell
      soma, axon hillock, and axon initial segment in the GCL and its border with the
      nerve fiber layer (NFL). Some axonal profiles have a dense undercoat and
      fasciculated microtubules, features that are characteristic of the axon initial
      segment in many neurons of both central and peripheral nervous systems. These
      features are confined to small- and medium-diameter (0.2-0.6 microns) axon
      profiles located near the GCL/NFL border and are not found on axonal profiles
      lying deep in the NFL, suggesting that the dense-coated region does not extend
      far along the axon and that the dense-coated region may be narrower than the
      distal part of the axon. The dense-coated region may correspond to the ganglion
      cell "narrow segment" recently described in a variety of species using light
      microscopic methods. The results presented here strengthen our previous
      hypothesis that GABA-immunoreactive neurons in the GCL provide direct synaptic
      input to ganglion cells near the site of action potential initiation.

PMID- 8296459
TI  - Disk shedding in the absence of a pigment epithelium in the lizard parietal eye.
AB  - The photoreceptors and pigment epithelia of vertebrate retinas rhythmically
      synthesize and degrade photosensitive membrane, but the origin of the signal to
      shed the outer segment tips remains unknown. The parietal eye of lizards contains
      cone-like photoreceptors but no pigment epithelium. Parietal eye photoreceptors
      synthesize new disk membrane in a manner similar to rods and cones and also shed
      their tips rhythmically. The shed material is then engulfed by lumenal
      macrophages. The signal to shed must originate in, or be transduced by, the
      photoreceptor.

PMID- 8296460
TI  - A system of regular ridges instead of nipples on a compound eye that has to
      operate near the diffraction limit.
AB  - A system of regular, radial ridges, spaced approx. 250 nm apart, is reported from
      the outer corneal surface of the eye of the tiny moth Leucoptera coffeella.
      Antireflective coatings in larger insects with flatter facets often take the form
      of corneal nipples. However, evidence is presented that in an insect whose eyes
      have to operate near the lower diffraction limit and possess strongly convexly
      curved corneae a radial arrangement of microridges is just as effective as
      nipples--and simpler to construct.

PMID- 8296461
TI  - Refractive state of the rhinoceros.

PMID- 8296462
TI  - Directional adaptation effects with contrast modulated stimuli.
AB  - In this study we investigated the directional selectivity of the mechanisms used
      to encode the motion of contrast modulated stimuli. Unlike luminance-domain
      stimuli, contrast-domain stimuli fail to generate convincing motion aftereffects.
      On the other hand, contrast-domain stimuli produce other direction specific
      adaptation effects that are as large as those produced by luminance-domain
      stimuli. The results of this study indicate that the dissociation between these
      two measures of directional selectivity might result from differences in the
      temporal nature of the test probe they employ. Specifically, it is suggested that
      the mechanisms which encode the motion of contrast modulated stimuli reveal their
      directional selectivity only when tested with a dynamic stimulus.

PMID- 8296463
TI  - Is the increased spatial uncertainty in the normal periphery due to spatial
      undersampling or uncalibrated disarray?
AB  - There are two possible causes for the elevated positional uncertainty of the
      peripheral field; undersampling by post receptoral arrays or uncalibrated
      disarray within post receptoral arrays. In order to assess the relative
      influences of these two factors to peripheral spatial uncertainty, we apply an
      approach which has enjoyed much success in the field of colour vision to examine
      the trade-off between position and contrast errors for spatial vision. We show
      that, if our positional uncertainty in the periphery is due to spatial
      undersampling, a correlated contrast inaccuracy should be present. We find no
      evidence for this expected linkage in the peripheral field at any spatial scale.
      We conclude that uncalibrated neural disarray rather than undersampling is the
      cause of peripheral positional uncertainty.

PMID- 8296464
TI  - The lateral inhibition of perceived contrast is indifferent to on-center/off
      center segregation, but specific to orientation.
AB  - When a central test patch C, composed of an isotropic spatial texture, is
      surrounded by a texture field S, the perceived contrast of C depends
      substantially on the contrast of the surround S. When C is surrounded by a high
      contrast texture with a similar spatial frequency content, it appears to have
      less contrast than when it is surrounded by a uniform field. Here, we employ two
      novel textures: T+ which is designed to selectively stimulate only the on-center
      system, and T-, the off-center system. When C and S are of type T+ and T-, the
      reduction of C's apparent contrast does not vary with the combination of T+, T-.
      This demonstrates that the reduction of C's apparent contrast is mediated by a
      mechanism whose neural locus is central to the interaction between on-center and
      off-center visual systems. We further demonstrate orientation specificity: the
      reduction of grating C's apparent contrast by a surround grating S, of the same
      spatial frequency is greatest when C and S have equal orientation. Using
      dynamically phase-shifting sinusoidal gratings of 3.3, 10 and 20 c/deg, we
      measured reduction of apparent contrast using different contrast-combinations of
      C and S. RESULTS: (1) S gratings, both parallel and perpendicular to C, cause a
      reduction in C's apparent contrast relative to a uniform surround. (2) In all of
      the viewing conditions, the reduction of apparent contrast induced by the
      parallel surrounds was at least as great as that induced by the perpendicular
      surrounds. Often it was much greater. (3) Orientation specificity increases with
      increasing spatial frequency and with decreasing stimulus contrast.

PMID- 8296465
TI  - A perturbation analysis of depth perception from combinations of texture and
      motion cues.
AB  - We examined how depth information from two different cue types (object motion and
      texture gradient) is integrated into a single estimate in human vision. Two
      critical assumptions of a recent model of depth cue combination (termed modified
      weak fusion) were tested. The first assumption is that the overall depth estimate
      is a weighted linear combination of the estimates derived from the individual
      cues, after initial processing needed to bring them to a common format. The
      second assumption is that the weight assigned to a cue reflects the apparent
      reliability of that cue in a particular scene. By this account, the depth
      combination rule is linear and dynamic, changing in a predictable fashion in
      response to the particular scene and viewing conditions. A novel procedure was
      used to measure the weights assigned to the texture and motion cues across
      experimental conditions. This procedure uses a type of perturbation analysis. The
      results are consistent with the weighted linear combination rule. In addition,
      when either cue is corrupted by added noise, the weighted linear combination rule
      shifts in favor of the uncontaminated cue.

PMID- 8296466
TI  - Visual search asymmetries in three-dimensional space.
AB  - Feature-conjunction search performance was investigated as a function of the
      target's location in three-dimensional (3-D) space. Ten subjects viewed a display
      that contained 36 shapes, one of which was the target. The targets were presented
      in one of four quadrants, three depths, and three eccentricities. On a given
      trial, nontarget distractor shapes were presented at the other 35 locations. The
      ability to find a target shape was best when it was presented in the upper and
      right visual fields and was closest to the fixation point in both its depth and
      eccentricity. These nonuniformities may be partly derived from the link between
      visual search and an extrapersonal attentional mechanism.

PMID- 8296467
TI  - The spectral properties of the two rod pathways.
AB  - Psychophysical and electroretinographic observations in normal and achromat
      observers suggest that rod flicker signals have access to at least two retinal
      pathways: one (pi 0), slow and sensitive, predominating at scotopic luminance
      levels; the other (pi'0), fast and insensitive, predominating at mesopic ones. We
      have measured steady-state flicker detection sensitivities on background fields
      ranging from 430 to 640 nm in normal observers. Our results suggest that cone
      signals can reduce the sensitivity of pi'0, but have comparatively little effect
      on pi 0. The pi'0 field sensitivities derived from these measurements have been
      fitted with linear combinations of the scotopic luminosity function, V' lambda,
      the M-cone spectral sensitivity function, M lambda, and the L-cone function, L
      lambda. These fits demonstrate a clear cone influence on pi'0, but they cannot
      tell us unequivocally whether the influence is from the M-cones, from the L-cones
      or from both. Accordingly, we made similar measurements in dichromats, who lack
      one of the two longer wavelength cone types. These measurements revealed an L
      cone influence on pi'0 in the deuteranope and an M-cone influence in the
      protanope. This suggests that both cone types can affect the sensitivity of pi'0.
      The finding that the steady-state cone signals reduce the sensitivity of pi'0 but
      have little effect on pi 0 could suggest that pi'0 signals travel through a
      faster cone pathway (with its own gain control at which both rod and cone signals
      can reduce rod threshold), while pi 0 signals travel through a separate rod
      pathway. However, it could simply reflect the fact that pi'0 predominates at
      higher luminances than pi 0 where the cone excitation level is inevitably
      greater. To examine the influence of the cones on pi 0 more closely, we: (i)
      produced transient cone excitation by alternating rod-equated 480 and 679 nm
      fields; and (ii) extended our steady-state measurements to include deep-red
      backgrounds of 650 and 680 nm. Both experiments revealed a small, but measurable
      influence of the cones on pi 0.

PMID- 8296468
TI  - Motion contrast and motion integration.
AB  - When a moving aperture contains a drifting grating, the perception of aperture
      movement is strongly affected by the grating movement. We have studied this
      interaction, using a moving circular patch of sinusoidal grating matched to the
      background in mean luminance. The circular window, or aperture, could be defined
      either by an abrupt transition from a full-contrast grating to the background
      (hard aperture) or by a two-dimensional Gaussian fall-off in contrast (soft
      aperture). The grating movement could be controlled independently of the aperture
      motion. Subjects judged the direction of the aperture movement (i.e. the movement
      of the patch as a whole). We find that an illusory motion of a stationary
      aperture can be induced depending on the direction of the grating drift. A hard
      aperture presented in the fovea appears to move in the direction opposite the
      grating movement, demonstrating simultaneous motion contrast. However, a soft
      aperture presented in the periphery appears to move in the same direction as the
      drifting grating, demonstrating motion integration (assimilation). These results
      are discussed in the context of interactions between short-range and long-range
      motion mechanisms and with respect to the significance of boundaries in
      determining the figure-ground relationship of motion signals.

PMID- 8296469
TI  - Visual processing delays alter the perceived spatial form of moving gratings.
AB  - This study shows that there are delays in processing high spatial frequencies
      relative to low frequencies, and that these may affect the perceived brightness
      profile of drifting waveforms. The stimuli were complex waveforms consisting of 2
      3 sinusoidal components, either drifting or stationary. The phase of the
      components was varied until the brightness profile of the waveform appeared as a
      square, triangle, ramp or bar. The results indicate that stationary waveforms are
      perceived veridically, but drifting waveforms are not. The harmonics of a
      drifting complex wave must be phase advanced, relative to the fundamental, in
      order to cancel motion-induced waveform distortions. This suggests that during
      visual processing the harmonics must be phase delayed, indicating that they are
      being processed more slowly than the fundamental. The most significant delays
      appear to be those between the fundamental and its second and third harmonic.
      Furthermore, the results show that the magnitude of the delays is dependent on
      the phase relationship between the components at perceptually significant points
      in the waveform: delays are less when the components are in sine phase than when
      they are in cosine phase. Separate experiments show that the detectability of
      phase shifts is least when the components are in sine phase. Together, these
      results may explain why drifting "sharp-edged" stimuli are not perceptually
      distorted: the human visual system appears to be relatively insensitive to phase
      shifts around square-wave phase and may therefore tolerate differences in the
      processing times of certain harmonics. A discussion of the possible origin of
      these processing delays is presented, together with the hypothesis that frequency
      dependent delays may reflect the spatiotemporal inseparability of cortical visual
      units.

PMID- 8296470
TI  - An oblique effect in parafoveal motion perception.
AB  - An observer's ability to discriminate the angular direction of a moving grating
      depends on the grating orientation. Observers can more accurately judge the
      angular direction of vertical or horizontal gratings than oblique gratings. We
      discovered that this oblique effect becomes very large at high spatial
      frequencies in the parafovea. Perceived direction was quantified with a direction
      matching task at spatial frequencies ranging from 7.6 to 22.6 c/deg. As spatial
      frequency increased, direction matches of oblique gratings deviated away from the
      diagonal and towards vertical or horizontal axes. Subjects reported that the
      higher spatial frequency gratings appeared as grainy noise, particularly at
      oblique orientations. Our results indicate that, in the parafovea, subjects
      perceive movement of high spatial frequencies mainly along principal meridians.
      One possible explanation for this effect is that the high frequency patterns are
      aliased by the irregular mosaic of parafoveal cones. The aliasing noise generated
      by irregular sampling contains spatial energy at all orientations, but perhaps
      only vertical and horizontal components of the noise are visible to the observer.

PMID- 8296471
TI  - Can we attend to large and small at the same time?
AB  - Evidence from several sources suggests that visual attention is tuned to stimulus
      scale. This tuning impairs performance when the observer must attend to more than
      one scale at a time. In experiments originally designed to measure the bandwidth
      of attention to stimulus scale, we have found tasks in which observers show no
      attentional tuning for scale. In separate blocks, observers located or identified
      targets in arrays of elements, either numbers in arrays of letters or static
      squares in arrays of flashing squares. Each display contained two arrays, either
      of the same scale or of different scales. The accuracy of locating the target
      element was lower in mixed-scale than in single-scale displays, but the accuracy
      of identifying the target was unaffected by a mixing of scales within the same
      display. This holds for both high-level discriminations--numbers vs letters--and
      low-level discriminations--static vs flashing. Thus, at least for identifying,
      one can attend to large and small at the same time. The difference in bandwidth
      between "what" and "where" implies that stimulus identification is not dependent
      on prior localization.

PMID- 8296472
TI  - Modelling the dependence of contrast sensitivity on grating area and spatial
      frequency.
AB  - We modelled the human foveal visual system in a detection task as a simple image
      processor comprising (i) low-pass filtering due to the optical transfer function
      of the eye, (ii) high-pass filtering of neural origin, (iii) addition of internal
      neural noise, and (iv) detection by a local matched filter. Its detection
      efficiency for gratings was constant up to a critical area but then decreased
      with increasing area. To test the model we measured Michelson contrast
      sensitivity as a function of grating area at spatial frequencies of 0.125-32
      c/deg for simple vertical and circular cosine gratings. In circular gratings
      luminance was sinusoidally modulated as a function of the radius of the grating
      field. In agreement with the model, contrast sensitivity at all spatial
      frequencies increased in proportion to the square-root of grating area at small
      areas. When grating area exceeded critical area, the increase saturated and
      contrast sensitivity became independent of area at large grating areas. Spatial
      integration thus obeyed Piper's law at small grating areas. The critical area of
      spatial integration, marking the cessation of Piper's law, was constant in solid
      degrees at low spatial frequencies but inversely proportional to spatial
      frequency squared at medium and high spatial frequencies. At low spatial
      frequencies the maximum contrast sensitivity obtainable by spatial integration
      increased in proportion to spatial frequency but at high spatial frequencies it
      decreased in proportion to the cube of the increasing spatial frequency. The
      increase was due to high-pass filtering of neural origin (lateral inhibition) and
      the decrease was mainly due to the optical transfer function of the eye. Our
      model explained 95% of the total variance of the contrast sensitivity data.

PMID- 8296473
TI  - An oscillation-based model for the neuronal basis of attention.
AB  - We propose a model for the neuronal implementation of selective visual attention
      based on the temporal structure of neuronal activity. In particular, we set out
      to explain the electrophysiological data from areas V4 and IT in monkey cortex of
      Moran and Desimone [(1985) Science, 229, 782-784] using the "temporal tagging"
      hypothesis of Crick and Koch [(1990a) Cold Spring Harbor Symposiums in
      Quantitative Biology, LV, 953-962; (1990b) Seminars in the neurosciences (pp. 1
      36)]. Neurons in primary visual cortex respond to visual stimuli with a Poisson
      distributed spike train with an appropriate, stimulus-dependent mean firing rate.
      The firing rate of neurons whose receptive fields overlap with the "focus of
      attention" is modulated with a periodic function in the 40 Hz range, such that
      their mean firing rate is identical to the mean firing rate of neurons in "non
      attended" areas. This modulation is detected by inhibitory interneurons in V4 and
      is used to suppress the response of V4 cells associated with non-attended visual
      stimuli. Using very simple single-cell models, we obtain quantitative agreement
      with Moran and Desimone's (1985) experiments.

PMID- 8296474
TI  - Update on therapy for atrial fibrillation.
AB  - This article reviews newer trends in the management of patients with atrial
      fibrillation. The roles of chronic antiarrhythmic therapy, anticoagulation, and
      nonpharmacologic treatments are discussed.

PMID- 8296475
TI  - Giant posterior inferior cerebellar artery aneurysm associated with foramen
      magnum syndrome.
AB  - The case of a giant distal posterior inferior cerebellar artery (PICA) aneurysm
      which caused foramen magnum syndrome is presented. A 67-year-old male was
      referred for evaluation of a posterior fossa mass lesion on MRI scan. Craniotomy
      was performed which revealed a giant and completely thrombosed aneurysm of the
      distal PICA, which was subsequently excised intact. This report adds giant
      aneurysm of the PICA to the list of posterior fossa lesions reported which cause
      foramen magnum syndrome.

PMID- 8296476
TI  - The gynecologist and treatment of carcinoma of the breast.
AB  - The treatment of breast carcinoma has traditionally been relegated to the general
      surgeon. The gynecologist, in his/her role of treating women's diseases, will
      likely become more involved in the future. This article describes the experience
      of one gynecologist in the treatment of carcinoma of the breast involving 234
      biopsies which were performed from January 1985 to December 1992. Invasive
      carcinoma was found in 81 of the cases, and five showed in situ carcinoma.

PMID- 8296477
TI  - The split in medicine.

PMID- 8296478
TI  - Control of capripoxvirus infections.
AB  - The capripoxviruses cause the most severe pox diseases of animals.
      Epidemiologically the diseases of sheep pox, goat pox and lumpy skin disease
      differ, but all three viruses may be mechanically transmitted by biting insects,
      and control without vaccination is extremely difficult in endemic areas. Recently
      developed live attenuated vaccines provide good, virtually lifelong, protection,
      which is dependent on stimulating cell-mediated immunity. Lumpy skin disease
      currently threatens to extend beyond its existing boundaries, causing concern and
      renewed interest in vaccine development. With the capripoxviruses showing great
      promise as vector vaccines, widespread use of a recombinant vaccine seems
      increasingly likely.

PMID- 8296479
TI  - Improved immunogenicity of recombinant vaccinia virus-anchored gp120 lacking
      gp41.
AB  - To produce a vaccine against human immunodeficiency virus-1 with improved
      immunogenicity, the transmembrane and cytoplasmic tail regions of human
      immunodeficiency virus-1 were replaced with those of the Vesicular Stomatitis
      Virus glycoprotein, and cloned into vaccinia virus. This recombinant vaccinia
      virus, vvE13, was compared to one expressing full length envelope gp160, vvE1.
      Env products of both were located on the cell surface. Antibody response,
      lymphocyte proliferation and cytotoxicity were better with vvE13 than with vvE1
      inoculated mice.

PMID- 8296480
TI  - Oral immunization with recombinant BCG induces cellular and humoral immune
      responses against the foreign antigen.
AB  - It has been shown recently that BCG can be used as a live recombinant vaccine to
      stimulate immune responses. Proliferative or cytotoxic T-cell responses against
      several viral proteins such as HIV Gag, Env or Nef were obtained after parenteral
      immunization with BCG expressing these proteins. Antibody responses were also
      obtained after immunization of mice with recombinant BCG strain which expressed
      lac Z under the control of a promoter sequence isolated from Mycobacterium
      paratuberculosis. We have used this recombinant vaccine in guinea-pigs to
      investigate the influence of various routes of immunization on the immunogenicity
      of a foreign antigen expressed by recombinant BCG. Guinea-pigs were immunized by
      oral, respiratory or intradermal routes and proliferative responses, delayed-type
      hypersensitivity and antibody responses specific for beta-galactosidase were
      followed for 16 weeks. Results demonstrated that humoral and cellular immune
      responses specific for beta-galactosidase can be produced in all groups of guinea
      pigs. However, the respiratory and especially the oral route of administration
      induced higher local and systemic immune responses than the intradermal route of
      immunization. Moreover, the oral immunization of mice with this recombinant BCG
      induced IgA responses which could be detected in both sera and intestinal
      secretions. Therefore, this study demonstrates for the first time that oral
      immunization with recombinant BCG can induce strong cellular and humoral immune
      responses.

PMID- 8296481
TI  - Efficacy of Brucella suis strain 2 vaccine against Brucella ovis in rams.
AB  - The protective efficacy against Brucella ovis of live vaccine Brucella suis
      strain 2 (S2) and Brucella melitensis strain Rev 1 has been evaluated in rams.
      Fourteen 4-month-old Brucella-free Aragonesa rams were vaccinated conjunctivally
      with 2 x 10(9) c.f.u. S2. Sixteen rams of the same breed, condition and age were
      conjunctivally vaccinated the same day with 1.6 x 10(9) Rev 1. Thirteen rams were
      unvaccinated controls. Eight months after vaccination all rams were challenged
      with 6 x 10(9) c.f.u. B. ovis and slaughtered 2 months thereafter for
      bacteriological and pathological studies. The percentage of infection in the
      group vaccinated with Rev 1 (43.7%) was significantly lower (p < 0.05) than that
      of the S2-vaccinated animals (78.6%) and unvaccinated controls (84.6%). No
      significant differences were found when comparing the percentages of infection
      corresponding to S2-vaccinated and control groups. The degree of infection
      (percentage of necropsy samples infected) was significantly lower in Rev 1
      vaccinated (13%) than in S2-vaccinated (36.9%) or control groups (47.4%) (p <
      0.001). However, no significant differences were found when comparing S2
      vaccinated and control groups.

PMID- 8296482
TI  - Avridine and LPS from Brucella ovis: effect on the memory induced by foot-and
      mouth disease virus vaccination in mice.
AB  - Foot-and-mouth disease is one of the more economically important diseases among
      meat-producing biungulate species. In contrast to natural infection, current foot
      and-mouth disease virus (FMDV) vaccines, prepared with inactivated virus and
      adjuvants, elicit short-lived protection. The immunomodulating effect on FMDV
      vaccines of avridine and lipopolysaccharide of Brucella ovis (LPS) was tested in
      a murine model. The duration of immunity, protection, stimulation of
      immunocompetent cells producing a long-lasting secondary response and
      immunoglobulin (Ig) isotypes were examined. The incorporation of either
      immunomodulator into aqueous and oil vaccines induced a long-lasting specific
      antibody response. The neutralizing titres and protection were significantly
      higher than those observed in animals immunized with control vaccines. Data
      collected from repopulation assays indicated that the immunomodulators used
      participate in the activation of immune cell populations involved in long-lasting
      memory. This resulted in an efficient B-cell secondary response even in the
      absence of T cells, which were necessary for the stimulatory effect of the
      immunomodulators in donor mice. Avridine and LPS stimulated IgG1, IgG2a and IgG2b
      production, which was correlated with the improvement of the protection induced
      by these vaccines.

PMID- 8296483
TI  - Immunopotentiation of local and systemic humoral immune responses by ISCOMs,
      liposomes and FCA: role in protection against influenza A in mice.
AB  - The immunogenicity and protective efficacy of an influenza A subunit vaccine
      preparation administered to mice in an aqueous form, or presented as
      immunostimulatory complexes (ISCOMs), liposomes or with Freund's complete
      adjuvant (FCA), were assessed in comparative studies with live infectious virus.
      Both intranasal and parenteral routes of administration were assessed. An enzyme
      linked immunosorbent assay (ELISA) was used to measure nasal wash and serum
      antibody responses in groups of unprimed mice, while protection was determined by
      the recovery of homologous influenza virus from mouse nasal washes and lung
      homogenates following challenge infection by the intranasal route. The results
      showed that parenteral administration of the influenza antigen preparations
      induced variable levels of both local and systemic antibodies at weeks 3, 7 and
      22 postimmunization. Although the overall greatest levels of antibody and
      protection were elicited in mice following live virus infection, formulation of
      influenza surface haemagglutinin (HA) and neuraminidase (NA) proteins into ISCOMs
      elicited high and persistent antibody responses and provided relatively good
      protection of the upper and lower respiratory tracts of these animals. The
      results also show a relatively poor effect of the subunit antigen preparations in
      promoting humoral immune responses and protection irrespective of the nature of
      their presentation, when given by the intranasal route.

PMID- 8296484
TI  - Killed Campylobacter elicits immune response and protection when administered
      with an oral adjuvant.
AB  - The heat-labile toxin (HLT) of enterotoxigenic Escherichia coli (ETEC) is a
      potent oral adjuvant. We determined whether the ETEC HLT could be mixed with
      killed campylobacter to induce an immune response protective upon subsequent
      challenge with live pathogens. Mice were immunized orally three times with 10(9)
      sonicated campylobacter with or without 25 micrograms of ETEC HLT, and humoral
      immune responses in intestinal lavage fluids measured by ELISA. Whereas 10(9)
      live bacteria induced strong intestinal IgA responses, killed bacteria did not
      unless ETEC HLT was also added. The magnitude of the antibody response was
      dependent on the amount of antigen given. The ETEC HLT given with bacteria also
      induced a potent cross-reaction with cholera toxin. The latter had an adjuvant
      effect in mice similar to that of ETEC HLT. Protection against colonization was
      studied in mice and rabbits. In contrast to non-immune animals, those given live
      organisms or sonicated cells mixed with ETEC HLT quickly cleared homologous, but
      not heterologous, Lior serotypes of Campylobacter upon challenge. These data show
      for the first time that ETEC HLT can potentiate an immune response to killed
      campylobacter that promotes a rapid clearance of live pathogens from the
      intestine.

PMID- 8296485
TI  - Co-dominant and reciprocal T-helper cell activity of epitopic sequences and
      formation of junctional B-cell determinants in synthetic T:B chimeric immunogens.
AB  - The identification of defined T-helper (Th) cell determinants, particularly those
      recognized in the context of several MHC or HLA haplotypes, and their use to
      provide effective carrier help to short synthetic constructs representing a B
      cell epitope have made it feasible to synthesize putatively potent immunogens.
      However, a number of crucial questions regarding immunogenicity of epitopic
      sequences need to be addressed before an optimally effective synthetic vaccine
      can be designed. The present study deals with the hybrid constructs incorporating
      a known B-cell epitope from the merozoite surface protein-1 (MSP-1) of a human
      malarial parasite, Plasmodium falciparum, and the promiscuous Th-cell epitope
      from tetanus toxin or from the circumsporozoite protein of P. falciparum. Here,
      we provide data which suggest that B- and T-cell determinants present in a hybrid
      construct could, in fact, provide reciprocal helper activity for antibody
      production; that antibodies to a Th-cell epitope may not necessarily block its
      helper function; and that junctional B-cell epitopes may be formed. All this may
      influence, in an unpredictable manner, the quality of protective immune response
      sought to be generated using the chimeric immunogens, with important implications
      for vaccine design.

PMID- 8296486
TI  - Use of the Vibrio cholerae irgA gene as a locus for insertion and expression of
      heterologous antigens in cholera vaccine strains.
AB  - Vibrio cholerae may be a particularly effective organism for use in delivering
      heterologous antigens to stimulate a common mucosal immune response. A live
      attenuated vaccine strain of V. cholerae was constructed from the ctxA deletion
      mutant 0395-N1, containing the B subunit of Shiga-like toxin I under the
      transcriptional control of the iron-regulated irgA promoter. The B subunit of
      Shiga-like toxin I is identical to the B subunit of Shiga toxin (StxB). irgA
      encodes the major iron-regulated outer membrane protein of V. cholerae, which is
      a known virulence factor for this organism. Clones of the structural gene irgA
      from the classical V. cholerae strain 0395, with the gene for the Shiga-like
      toxin I B subunit inserted under the control of the irgA promoter, were used to
      introduce an internal deletion of irgA into the chromosome of 0395-N1 by in vivo
      marker exchange, using the suicide vector plasmid pCVD442. This plasmid contains
      the sacB gene from Bacillus subtilis, which allowed positive selection for loss
      of plasmid sequences on exposure to sucrose. The construction of vaccine strains
      was confirmed by Southern hybridization studies and outer membrane protein
      analysis. The expression of StxB in the vaccine strain VAC2 following growth in
      high- or low-iron conditions was shown to be tightly iron-regulated by Western
      blot analysis and by quantification of StxB using a sandwich enzyme-linked
      immunosorbent assay. The production of StxB by VAC2 under low-iron conditions was
      greater than that of the reference strain Shigella dysenteriae 60R.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8296488
TI  - Serious hepatitis B vaccine adverse reactions, are they immune-mediated?

PMID- 8296487
TI  - Quantitative and qualitative analysis of anti-tetanus toxoid antibody response in
      the elderly. Humoral immune response enhancement by thymostimulin.
AB  - In order to explore the humoral primary and secondary response to tetanus toxoid
      (TT), and to define the possible immunopotentiating effect of the thymic hormone
      thymostimulin, we studied 13 elderly people, selected according to the Senieur
      Eurage protocol, vaccinated against TT, an antigen never encountered before. Six
      of them were treated with thymostimulin before and during the immunization
      protocol. Specific anti-TT antibody level measurement and spectrotypic analysis
      were performed on the sera collected from the subjects at different times over
      the immunization protocol. In addition, spontaneous in vitro production of anti
      TT antibodies as well as cutaneous delayed hypersensitivity reactions were also
      studied. Only one patient showed a detectable humoral immune response after the
      first immunization. After the booster, four of six thymostimulin-treated
      individuals, compared with only two of seven controls, showed in vivo anti-TT
      humoral response; at the same time, spontaneous anti-TT production was detected
      in peripheral blood mononuclear cells from five of six thymostimulin-treated
      individuals but only three of seven untreated controls. These differences were
      highly significant (p < 0.0001). In addition, only in thymostimulin-treated
      subjects were the levels of serum anti-TT antibodies 14, 21 and 28 days after the
      booster significantly (p < 0.05) higher than the baseline values. The
      spectrotypic analysis of anti-TT antibodies performed by isoelectric focusing and
      reverse blotting showed total agreement with the results from enzyme-linked
      immunosorbent assay.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296489
TI  - Scarification with a vaccinia-influenza recombinant does not stimulate IgA unless
      the animals auto- or cross-inoculate their nasopharynxes.

PMID- 8296490
TI  - Effects of two low-dose oral contraceptives on erythrocyte superoxide dismutase,
      catalase and glutathione peroxidase activities.
AB  - The effect of a triphasic combination of ethinyl estradiol and levonorgestrel
      upon activities of superoxide dismutase, catalase and glutathione peroxidase in
      erythrocytes was compared to that of a preparation that contained ethinyl
      estradiol and desogestrel on the 21st day of a control cycle, of the third cycle
      of treatment with ethinyl estradiol/levonorgestrel or ethinyl
      estradiol/desogestrel (14 volunteers each), and of the third cycle of a 3-month
      washout period. Significant decreases were found in the activities of superoxide
      dismutase, catalase and glutathione peroxidase in erythrocytes with both
      preparations. The effect of desogestrel on the activities of the superoxide
      dismutase, catalase and glutathione peroxidase is similar to that of
      levonorgestrel. These data suggest that low-dose oral contraceptives, by
      decreasing the activities of antioxidant enzymes and by enhancing the lipid
      peroxidation, increase the risk of cardiovascular disease.

PMID- 8296491
TI  - [Treatment of endometriosis with the GnRH analog triptorelin with special
      reference to the effect on bone density].
AB  - 27 patients of the department of gynecology and obstetrics of the university of
      Essen received a six month therapy with the GnRH-analogon triptorelin because of
      endometriosis diagnosed by laparoscopy. All the patients experienced not only a
      significant improvement in their subjective symptoms but also in their rAFS-score
      which was used to classify the severity of the endometriosis of our patients. We
      could also show that no patient experienced any severe side effects under the
      therapy and those side effects such as hot flushes or sweating, which appeared,
      were almost tolerated very well by the patients. None of the patients did leave
      the study because of the side effects. We were also able to demonstrate that
      under the therapy there was no significant loss of the bone density. The
      introduction of the GnRH-analogon triptorelin is therefore a major step forward
      in the effective therapy of patients suffering from endometriosis.

PMID- 8296493
TI  - [Endoscopy of the preperitoneal interstitium--a new approach for
      colposuspension].
AB  - The successful use of fibrin sealant in Colposuspensive surgery has been proved
      in long-term follow-up studies, avoiding disadvantages and risk of the suture
      technique. We introduce a new technique allowing us to perform colposuspension by
      minimal invasive surgery. By endoscopic approach of the pre-peritoneal interstice
      (Retziiscopy), a correct preparation of urinary bladder, urethra, vaginal fascia
      and Cavum Retzii is possible. Following preparation, colposuspension by means of
      fibrin sealant can be performed.

PMID- 8296492
TI  - [Chlamydia trachomatis: screening within the scope of prenatal care and rapid
      diagnosis in threatened premature labor].
AB  - Cervical infection with Chlamydia trachomatis during pregnancy is related to the
      incidence of preterm labour and preterm rupture of membranes, causing elevated
      neonatal morbidity and mortality. The present study reports our two-years
      experiences with a general screening on Chlamydia infection in prenatal care as
      well as diagnostic possibilities in case of imminent preterm delivery. In the
      examined population of totally n = 263 pregnant women attended in our prenatal
      care unit, the prevalence of cervical Chlamydia infection was 3.4%. Among the
      screened asymptomatic women (n1 = 179) 2.8% had positive findings. Among n2 = 84
      patients with preterm labour and/or preterm rupture of membranes 4.8% revealed
      cervical infection. Specially in the acute situation of imminent preterm
      delivery, an immunological bedside assay (Clearview Chlamydia, R) tested in 203
      cases versus the tissue culture as reference method proved helpful. Its
      sensitivity was 0.8, specificity 0.99. The test allowed to prove or exclude
      chlamydial infection within only 30 minutes.

PMID- 8296494
TI  - Diagnosis and follow-up of atypical hyperplasia of corpus endometrium--a critical
      methodological investigation.
AB  - Within 5 years 181 patients were diagnosed with grade I and grade II atypical
      hyperplasia (AH) in the curettage material of 4193 specimens at the University
      Department of Gynecology and Obstetrics in Tubingen. In 62.6% of grade I and in
      38.8% of grade II AH, concomitant endometrial polyps were observed, rarely cystic
      alterations as well. Especially with AH grade II, most polyps exhibited
      epithelial proliferation. Plurifocality and in situ residuals of AH were seen
      (grade I 38.5%, grade II 77.3%). In the same time period 345 endometrial
      carcinomas were found. Due to embedding techniques and the observation that only
      approximately 60% of the cavum uteri surface is reached via curettage, diagnostic
      security is quite limited. It has been published that women with AH have a higher
      risk of developing endometrial carcinoma. A control curettage after 6 months or a
      wide indication for hysterectomy is recommended after atypical endometrial
      hyperplasia has been demonstrated.

PMID- 8296495
TI  - [Plasma concentrations of non-esterified fatty acids and lipids in high-dose
      medroxyprogesterone therapy of metastatic breast cancer].
AB  - The objective of this study was to investigate the influence of high dose MPA on
      serum cholesterol, triglyceride, phospholipids as well as free fatty acids given
      to 17 patients with metastatic breast cancer. Before the therapy, the patients
      with cancer revealed higher level in serum cholesterol, triglyceride,
      phospholipids and C 12:0, C 18:0 as we found it in the control (13 patients
      without cancer). There was no significant change in lipid parameters by treatment
      with MPA whereas cortisol decreases and insulin increases under therapy. The
      results are discussed under biochemical aspects.

PMID- 8296496
TI  - [Case report of squamous epithelial cancer of the female breast].
AB  - A report its given about one case of squamous cell cancer of female breast. The
      authors analyse the therapeutic management and prognostic factors of this
      disease.

PMID- 8296497
TI  - [Primary malignant melanoma of the uterine cervix--case report and review of the
      literature].
AB  - We present a case of primary malignant melanoma of the cervix uteri. The
      prognosis of this very rare tumor is rather poor. Radical abdominal hysterectomy
      combined with partial colpectomy, bilateral adnexectomy and dissection of the
      pelvine lymph-nodes seems to improve the clinical outcome even if an additional
      brachytherapy is added.

PMID- 8296498
TI  - Endocrine studies in a case of profound virilization of a woman due an androgen
      producing granulosa cell tumor.
AB  - In a case of androgen-producing granulosa cell tumor in a 29-year-old woman with
      profound virilization, diagnosis by determination of serum hormone levels is
      described. The removal of the tumor is followed by a normal endocrine profile and
      pregnancy eight weeks later.

PMID- 8296499
TI  - [The end of home delivery midwifery in German-speaking sections of Upper Italy].
AB  - The German language islands in Northern Italy are a string of remote mountain
      villages stretching from Aosta in the west to Friuli in the east. These villages
      were founded in the middle ages by settlers from present-day Switzerland, Austria
      and Germany. The descendents of these settlers, almost all of them farmers, speak
      antiquated form of German and have maintained traditions that have long died out
      in the countries of their ancestors. The transformation from home births attended
      by the midwife to hospital births attended by a gynecologist took place in rural
      Italy in the 1960s. The aim of this study was investigate how this change took
      place in the language islands in their combination of geographical and linguistic
      isolation. The language islands of Macugnaga (Novara), Luserna and Val Fersina
      (Trento), the 13 Communities (Verona), Sappada (Belluno) and Timau (Udine) were
      visited and semi-structured interviews with midwives and other inhabitants in
      German dialect and in Italian were tape recorded. Home births accounted for
      almost 100% of all births in the language islands in the 1950s and ceased to
      exist after 1973. The German-speaking population stayed longer with home births
      than the Italian inhabitants of the same villages. Several reasons, practical and
      to a lesser extent psychological account for this behaviour: until 1962 the
      farmers' insurance policy did not cover hospital births, extensive road building
      to make the villages accessible all year round began after the flood summer of
      1966, the inhabitants of the language islands felt they were considered as a
      backward rural minority in the hospitals of the towns.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8296500
TI  - [The surgical treatment of dysembryogenetic tumors in the sella-sphenoid location
      by a transnasal-trans-sphenoid approach].
AB  - In 1979-1993, a total of 1,320 patients with tumors of various histological
      patterns were operated on by transnasal and transsphenoidal access. Among them,
      57 patients had dysembryogenetic tumors: craniopharyngiomas (n = 37), chordomas
      (n = 10), angiofibromas (n = 6), Rathke's pouch cysts (n = 2), epidermoid cysts
      (n = 2). Eleven patients were operated on by a combined access (transcranial,
      then transnasal). The paper gives in detail the clinical aspects, X-ray
      diagnostic features of dysembryogenetic tumors of sellar-sphenoidal site,
      identifies their basic growth variants. It also describes the specific features
      of the access and operation techniques. Indications and contraindications for
      surgery have been developed. Tumors were totally and subtotally removed in 82.5%
      of patients. Visual improvements were observed in 74.4%. It is concluded that the
      transnasal and transsphenoidal access maybe used as the major method of surgical
      treatment and combined surgical treatment of dysembryogenetic tumors of sellar
      sphenoidal site.

PMID- 8296501
TI  - [The contrast enhancement of brain and spinal cord tumors using Gd-DTPA in
      magnetic resonance tomography with an extra-low magnetic-field intensity].
AB  - The contrasting agent Gd-DTPA (Magnevist, Schering AG, Germany) was tested when
      used in magnetic resonance tomography using extra-low (0.04 T) magnetic field
      intensity in 68 patients with various brain and spine tumors. The agent was
      injected intravenously in a dose of 0.1 mmol/kg. No complications were found. The
      tests showed its high efficiency in the diagnosis of brain neoplasms
      (particularly in malignant intracerebral disorders, meningiomas and neurinomas).
      Benign astrocytomas induced no noticeable signal intensification on post
      contrasting T1-weighed tomograms. In all cases of spinal tumors, the application
      of Gd-DTPA could specify the extent of tumor invasions, the presence of cysts and
      identify accessory tumor nodes in one case.

PMID- 8296502
TI  - [The dynamics of the clinical and computed tomographic changes in brain
      contusions].
AB  - Follow-up clinical and computed tomographic studies were performed in 116
      patients with acute craniocerebral injury. Out of them, 101 victims were followed
      in the intermediate and late periods during 1 to 2 years. The results of surgical
      and drug treatments of patients with moderate (n = 30) and severe (n = 86) injury
      were analyzed. Despite favourable prognosis of acute craniocerebral injury, the
      patients were shown to develop mild, moderate, and severe posttraumatic computed
      tomographic changes. Varying decreased working ability and disability developed
      in patients depending on the magnitude of posttraumatic brain changes.

PMID- 8296503
TI  - [Clinico-neuropsychological observations of patients with aresorptive
      hydrocephalus].
AB  - Clinical and neuropsychological examinations were made in 33 patients with post
      bleeding hydrocephalus. The neuropsychological syndrome in aresorptive
      hydrocephalus due to ruptures both of arterial aneurysms and of arteriovenous
      malformations was shown to appear as dysfunction of frontal and diencephalic
      regions of the brain. It included disorientation, inertness, spontaneity,
      perseveration, awakening fluctuations, persistent memory dysfunctions and
      sluggish mentality. Neuropsychological symptoms were greatly dynamic. The level
      of awakening and orientation underwent rapid changes. The syndrome showed more
      frequently a milder regressive course in aresorptive hydrocephalus caused by
      ruptures of arteriovenous malformations than by those of arterial aneurysms;
      asymptomatic cerebral ventricular dilation being observed.

PMID- 8296504
TI  - [The use of inflow-outflow drainage after cerebral operations].
AB  - The paper provides strong evidence for the use of inflow-outflow drainage after
      brain operations and presents an analysis of 255 cerebral operations using
      various draining modes. The inflow-outflow drainage after brain operations is
      found to be promising in terms of clinical manifestations. The authors propose
      their own draining tube for inflow-outflow drainage. A comprehensive macro- and
      microscopic study of dialysis fluid is recommended. The presence of visible
      impurities in the dialysate, daily mass of cerebral detritus and the functional
      activity of granulocytes and mononuclear cells were assessed. A significant early
      sign has been identified when the inflow-outflow drainage system was applied
      during occurring local infectious complications by analysing the adhesive
      properties of mononuclear and polynuclear phagocytes of the dialysate.

PMID- 8296505
TI  - [Cerebrolysin electrophoresis in the correction of the mental defects in
      neurosurgery patients].
AB  - Two routes of cerebrolysin administration--intravenous (a routine mode) and
      electrophoretic (the mode developed at the N. N. Burdenko Institute of
      Neurosurgery, Russian Academy of Medical Sciences)--were evaluated by using a
      standardized rating schedule of neurological and neuropsychological studies. The
      findings indicate that these routes of administration show the same therapeutical
      effect, the latter route of administration is simpler and causes no pain in
      patients.

PMID- 8296506
TI  - [The diagnosis of vascular micromalformations in the brain].
AB  - Ninety cases with cerebrovascular micro-malformations were analyzed. These
      abnormalities amount to 5.3% of the total number of patients with arteriovenous
      malformation. These include various vascular defects from 0.5 to 1.0 cm. Most of
      them run as strokes (80%); the others have a pseudotumorous course. Angiography
      reveals 60.5% of cerebrovascular micro-malformations. In other cases they are
      undetectable or their identification requires functional and gross angiography.
      Computed tomography and magnetic resonance tomography reveal intracranial
      hemorrhages from cerebrovascular micro-malformations, without identifying the
      latter. They cannot differentiate a tumor from parenchymatous hemorrhages from
      cerebrovascular micro-malformations in 37.7%. The greater diagnostic difficulties
      arise in subtentorial cerebrovascular micro-malformations having a pseudotumorous
      course. In these cases they are angiographically invisible, and CT (MRT)
      diagnosis prior to surgery is a volumetric brain formation, providing no
      specification of the process.

PMID- 8296507
TI  - [AIDS and the surgical specialties].

PMID- 8296508
TI  - [A. I. Arutiunov and military field neurosurgery (on the 90th anniversary of the
      birth of A. I. Arutiunov)].

PMID- 8296509
TI  - [Microvascular compression of the accessory nerve in torticollis spastica].
AB  - The paper deals with the pathogenesis of torticollis spastica and potential modes
      of their treatment. The findings indicate that changes in the root of nerve XI
      are essential in the pathogenesis of this abnormality. Despite comparatively
      small materials, much higher efficiency of micro-decompression of the accessory
      nerve is shown.

PMID- 8296510
TI  - [The treatment of severe peripheral vertigo by the intracranial ligation of the
      vestibular portion of the 8th nerve].
AB  - Eight patients with severe peripheral vestibular vertigo refractory to other drug
      and surgical treatments underwent intracranial ligation of the vestibular nerve
      VIII portion. All the patients had been operated on the middle and internal ears
      many times (from 12 to 15 operations) for chronic purulent otitis (5 patients),
      cholesteatomas, 2-3 attempts had been made to destruct the labyrinth; shunting of
      the endolymphatic sac was made 2-3 times in patients with Meniere's disease. In
      all the patients, severe peripheral vestibular syndrome was associated with
      central nervous disease, mainly formations of the cerebellopontile angle due to
      secondary arachnoiditis. After ligation of the vestibular nerve VIII portion,
      good results were achieved in 7 out of the 8 patients, but one had a satisfactory
      effect. The paper shows indications and contraindications for intracranial
      ligation of the vestibular nerve VIII portion. It also emphasizes that the
      operation is effective, but it should be effected by very strict and limited
      indications when all other treatments are ineffective and vertigo is critical.

PMID- 8296511
TI  - [pH-metric variables in gastroesophageal reflux in asthmatic patients].
AB  - As there is an increased incidence of gastroesophageal reflux (GER) in asthmatic
      patients compared with the normal population, in the present trial we have tried
      to establish the following: 1) Possible differences in pH-metric variables
      between patients with GER and asthma, and asthmatic patients with or without GER
      2) The usefulness of simultaneous evaluation and correlation of reflux episodes
      with the respiratory peak flow (EPF) in asthmatic patients. 31 patients divided
      in four groups were compared. A) 16 patients with typical symptoms of GER without
      respiratory symptoms. B) 10 asthmatic patients with GER symptoms. C) 5 asthmatic
      patients without GER symptoms. D) 15 asthmatic patients who represents the sum of
      B and C. In all patients ambulatory computerized, four hours pH recordings were
      obtained after standard meal. The study was divided in two equal periods (upright
      and recumbent). The EPF was measured before starting the study and every 20 min
      during the recumbent period. From de following pH-metrics variables: total number
      of reflux episodes, percentage of recording time when intra-oesophageal pH < 4 in
      the upright position or recumbent position and for the total period, duration of
      longest reflux episode, number of episodes longer than five minutes, and
      correlation between reflux episodes and patients symptoms. Only differences were
      seen when the time of the longer period with GER and the number of patients with
      more than five minutes episodes were compared between groups A and D. From the
      results we conclude that the GER in asthmatic patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8296512
TI  - [Infections during the hospitalization of patients with liver cirrhosis].
AB  - We studied retrospectively the clinical records of 291 hospital patients with
      liver cirrhosis, 95% of which was alcohol related. Within this group, 114
      patients presented 155 episodes of infection in 144 separate hospital admissions.
      In a previous communication, we pointed out that although infection was the
      fourth cause of admission, it was the main cause of death in this group. The main
      incidence of infection was among the female group. The most common infections
      episodes were respiratory and bacterial spontaneous peritonitis (BSP). On
      admission, 57% of the patients were diagnosed as belonging to the C Child group;
      38% presented sepsis and 22% were hospitalary infections. The most frequent
      infections were respiratory and BSP. We obtained bacteriologic documentation in
      55% of the episodes with prevalence of Gram negative bacilli (E. coli), with high
      relative frequency of neumoccocus. The most frequent complications were related
      to hepatic insufficiency. Global death rate was 27.1%, while nosocomial death
      rates were 42.1% and 40.9% for patients with Child C. We observed the highest
      incidence of mortality in patients with SBP and non localized bacteriemia.
      Survival rates were 42% for 2 years and 18% for 5 years. In summary, we stress
      the relevancy of checking the presence of infection systematically in every
      cirrhotic patient with encephalopathy and/or renal insufficiency without
      justifiable cause.

PMID- 8296513
TI  - [Radioisotopic evaluation of alginic acid/antacid effect on the prevention of
      pathologic gastroesophageal reflux (GER)].
AB  - In this study the antireflux effect of Antacid/Alginic Acid compound (Batynid
      (R)) was prospectively evaluated assessed by radionuclide technique. Patients
      were divided in 2 groups: mild esophagitis 13 patients and severe esophagitis 13
      patients. The radionuclide study was done before and posterior ingestion of the
      compound evaluating duration, severity and number of the reflux episodes. The
      results show no significant differences comparing gastroesophageal reflux pre and
      post Batynid, in both group of patients, considering all parameters studied.

PMID- 8296514
TI  - [Homes for the aged. Are they a high risk population for hepatitis B?].
AB  - In a previous study we observed a high prevalence of infection with hepatitis B
      virus (HBV) among nurses and maids of the elder's home at the Lincoln Town
      Hospital, Lincoln, province of Buenos Aires, Argentine Republic. The purpose of
      this study was to know the prevalence of infection with HBV and analyze the
      serologic pattern found in old people of the home. We studied 38 people of both
      sexes, older than 60 years, who live at the home. The control group was formed
      with 91 people with the same characteristics but from the ambulatory clinic. In
      both groups anti-HBc, anti-HBs and AgHBs were detected by ELISA method. Results
      were: 3 subjects (7.9%) in the studied group and 6 (6.5%) in the control group
      presented markers repeatedly. The was no significant statistic difference between
      both groups (P 0.05). The old people from the elder home of this city, are not in
      great danger of HBV infection. We relate the high prevalence among nurses and
      maids with labor and extra labor factors and not with their specific work in this
      elder home.

PMID- 8296515
TI  - [Articular and extraarticular involvement in inflammatory bowel diseases].
AB  - Idiopathic inflammatory bowel disease include basically two disorders: ulcerative
      colitis and Crohn's disease. Both diseases are chronic and of unknown etiology
      and extraintestinal manifestations are seen in a high number of these patients.
      We studied 18 patients (7 female, 11 male) with previous diagnosis of
      inflammatory bowel disease (14 ulcerative colitis, 2 Crohn's disease, 1
      pancolitis, 1 ulcerative proctitis) in order to search for extraintestinal
      manifestations with emphasis on osteoarticular and ocular involvement. The mean
      age at the time of diagnosis of the inflammatory bowel disease was 44 years
      (range 20 to 71 years). Mean time duration of the inflammatory bowel disease was
      7 years (range 1 to 24 years) and of the articular manifestations 3.2 years
      (range 1 to 8 years). The osteoarticular manifestations developed after the
      diagnosis of the bowel disease in all but one patient (simultaneously) 17/18
      patients had artralgias, 7/18 lumbalgia, 3/18 talalgia, 1/18 knee arthritis.
      (table I) Only six of the 17 patients with orteoarticular involvement has
      simultaneous activity of the underlying bowel disease. All the 18 patients were
      taking 2 g/day of sulfasalazine. Radiographic screening in all patients revealed
      sacroiliitis in 10. (table II) Of the 10 radiographic sacroiliitis 4 were grade I
      (confirmed by technetium phosphate scans, 2 were grade II and 4 grade III-IV.
      Three of the ten patients with radiographic sacroiliitis were asymptomatic (table
      II). Axial computed tomography was performed done in two patients: a) in one case
      to exclude osteitis condensens ilii, and b) in the other case to exclude septic
      arthritis. The severity of the sacroiliac damage was related with a longer
      duration of the inflammatory bowel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296516
TI  - [Lead: histopathological findings in experimental contamination].
AB  - The aim of the present paper is to show lead toxicity and cell deposition of
      concentrations lower than those regarded as toxic on an experimental model with
      rats C3Hs., forty five grams-rats were used. A standard diet was administered
      together with water ad-libitium, containing very low doses of lead acetate which
      was constantly administered and at fixed periods. Light and electron microscopy
      were used to study the liver and the spleen. These organs are considered to
      harbour a great amount of constant macrophages with phagocytic function. The
      findings showed lesions and lead deposits which confirmed the causative agent as
      well as its toxic contaminating action.

PMID- 8296517
TI  - [Synchronous lesions in advanced colorectal cancer].
AB  - From jan '82 to jun '91 were done 3701 colonoscopic procedures. Of these, we
      arrived to cecum in 283 patients (pat) (51.1%) (male: 175 pat; female: 108 pat)
      in the first six months after the diagnostic of the colorectal cancer (CRC). The
      localization of the primary CRC was: rectum: 17.7%; left colon: 37.8% and right
      colon: 44.5%. 105 synchronical polyps (p) were seen in 87 pat (30.7%): 61 pat
      with 1p; 16 pat with 2 p and 10 pat with 3 p. Adenomas: 50/105 p (56.19%). Early
      cancer was histologically confirmed in 11/105 p (11/59 p adenomas). The
      distribution of early were 5/11 in the same colon segment ant 6/11 in the
      different colon segment. 1 pat has 3 early cancer. Synchronic advanced colorectal
      cancer (ACC) was seen in 9 pat (M/F = 2/1). All of these in different segments.
      In conclusion, the high frequency of the premalignant (adenomas) an malignant
      (early and advanced cancer) lesions, and the high risk of these in different
      segments of the large bowel, shows the colonoscopy is the most efficient method
      in the detection of the synchronical lesions of the colorectal cancer.

PMID- 8296518
TI  - [Cesar Roux and his Roux-en-Y anastomosis].
AB  - During the last 100 years, since Cesar Roux (1857-1934) began utilizing his "Loop
      en-Y" procedure for gastric outlet obstruction, this technique fell into
      disfavour but later, with the vagotomy, it was adapted for multiple applications.
      The greatest factor in its revival has been the treatment of postgastrectomy
      sequels, including alkaline reflux gastritis, reflux esophagitis, dumping and
      other syndromes. Additionally Roux-en-Y anastomosis has been used to drain
      diverse organs as the biliary tract, pancreas and esophagus. The main
      complication of loop-en-Y is the Roux syndrome, secondary to gastric or efferent
      jejunal stasis, or both. As the centennial of Roux's first use of his eponymic
      procedure approaches its seems appropriated to remind its memory as a part of our
      surgical inheritance.

PMID- 8296519
TI  - [Asymptomatic cholecystoduodenal fistula in a patient with diabetes mellitus and
      primary hypothyroidism: report of a case].
AB  - The case of a 60-year-old woman with diabetes mellitus type II and primary
      hypothyroidism, who presented a clinical picture compatible with intestinal
      obstruction is reported. An abdominal sonogram revealed acute calculous
      cholecystitis and ileus. A plain film of the abdomen showed dilatation of small
      bowel loops. She underwent celiotomy, once stabilized, and gallstone
      ileus+cholecystoduodenal fistula were diagnosed intraoperatively. Resection of
      the ischemic segment of distal jejunum and the stone, cholecystectomy and primary
      repair of the fistula were performed. In spite of the systemic complications
      (metabolic, cardiovascular and pulmonary), that appeared postoperatively, the
      patient had a favorable outcome. This patient had an acute calculous
      cholecystitis and a spontaneous biliary-enteric fistula with intestinal
      obstruction, without previous symptoms of biliary tract disease preceding the
      episode of bowel obstruction.

PMID- 8296521
TI  - [Helicobacter pylori: to treat or not to treat?].

PMID- 8296520
TI  - [Treatment with biofeedback for fecal incontinence].

PMID- 8296522
TI  - Acetazolamide-responsive hereditary paroxysmal ataxia: report of a new family.
AB  - Five family members were examined because of occurrence since childhood of
      recurrent episodes characterized by vertigo, dysarthria and gait ataxia. Analysis
      of the pedigree was consistent with an autosomal dominant mode of inheritance.
      Though asymptomatic between attacks, all the patients presented on examination a
      gaze-evoked and rebound nystagmus associated with a saccadic pursuit, a deficient
      optokinetic response and an inability to suppress the horizontal oculo-vestibular
      reflex by fixation; hypermetric saccades and truncal ataxia were also present in
      most of them. A sixth family member, aged 6 years, was found to present a gaze
      evoked nystagmus but was completely asymptomatic. Response of the attacks to
      acetazolamide therapy (250 mg twice a day) was assessed in two patients and was
      either partial or complete. A positron emission tomography (PET) study was
      realized between ataxic spells in one patient and demonstrated a decrease of
      glucose metabolism in the whole cerebellum, the inferior part of the temporal
      lobes and the thalami. These PET data as well as the detailed neuro
      ophthalmological findings bring new informations about acetazolamide-responsive
      hereditary paroxysmal ataxia, a rare but probably often misdiagnosed and
      treatable disorder.

PMID- 8296523
TI  - Wernicke's encephalopathy and central pontine myelinolysis induced by hyperemesis
      gravidarum.
AB  - A 21-year-old woman developed hyperemesis gravidarum, complicated by Wernicke's
      encephalopathy and central pontine myelinolysis. For the latter, time course of
      the lesions on magnetic resonance imaging suggests a pathogenetic role for
      hypophosphatemia rather than for hyponatremia.

PMID- 8296524
TI  - [Age and type of aphasia].
AB  - According to many studies, Broca's (or non fluent) aphasic patients are younger
      than Wernicke's (or fluent). Different hypotheses have been proposed to explain
      this age difference. However, since the studies in which an age difference was
      observed have not controlled all the variables--such as schooling and handedness-
      that may have an influence on speech and language impairments following cerebral
      lesion, it is legitimate to ask whether or not the explanations proposed are of
      any relevance. Accordingly, the present study aimed to investigate the age
      difference between Broca's and Wernicke's aphasics while achieving better control
      over potentially confounding variables. The subjects (9 Broca's and 14
      Wernicke's) were selected from a data base according to the following selection
      criteria: aphasia type, handedness, localization of lesion and etiology (first
      CVA). The two groups revealed to be equivalent for sex distribution and
      schooling; post onset time was superior to three weeks for all subjects but one.
      Results showed that the distribution of age between Broca's and Wernicke's group
      were significantly different: there was a small representation of Broca's
      aphasics in older subjects while Wernicke's aphasia occurred at all ages.

PMID- 8296525
TI  - Acute esotropia from small thalamic hemorrhage.
AB  - A 74 year-old patient developed transient acute esotropia, upward gaze palsy and
      imbalance of standing and gait. Computed Tomography (CT) demonstrated a small
      left thalamic hemorrhage in the absence of midbrain lesions. The role of thalamic
      lesion in the genesis of monocular supranuclear palsy is discussed.

PMID- 8296526
TI  - Transient atrial fibrillation associated with ischemic pontine stroke. Case
      report.
AB  - Atrial fibrillation (AF) and other cardiac arrhythmias may occur after stroke in
      absence of cardiac disease. We report a case of pontine ischemic stroke with
      paroxysmal atrial fibrillation of spontaneous resolution. Cardiac investigations
      were normal. We propose that the AF was the consequence of the stroke.

PMID- 8296527
TI  - Prolonged muscular flaccidity: frequency and association with unilateral spatial
      neglect after stroke.
AB  - The frequency of prolonged muscular flaccidity (PMF) was examined in a series of
      stroke patients in chronic phase suffering from hemiplegia with minimal
      spontaneous recovery (MSR). The results indicated that in such a population with
      poor motor recovery, PMF was significantly more frequent than spasticity. PMF was
      found to be associated with left-sided hemiplegia and unilateral spatial neglect.
      The minimal spontaneous recovery of the series of stroke patients we studied
      could be dependent on the interaction of three negative prognostic factors: left
      sided hemiplegia, unilateral spatial neglect and prolonged muscular flaccidity.

PMID- 8296528
TI  - Hemiplegia in posterior cerebral artery strokes.
AB  - Hemiplegia is an unusual presenting feature of posterior circulation strokes. We
      report five cases who presented with hemiplegia and in whom CT scans revealed
      evidence of infarcts in posterior cerebral artery territory.

PMID- 8296529
TI  - Endovascular management of carotid cavernous fistulae: observation on
      angiographic and clinical results.
AB  - Twenty-five patients with carotid cavernous fistulae (CCFs) were managed at our
      institute during a five-year period. Transarterial and transvenous treatment of
      traumatic carotid cavernous fistulae using the detachable balloon technique was
      performed in 21 patients resulting in angiographic and clinical cure in 20
      patients and fatal outcome in one patient following venous rerouting. Surgical
      ligation of the infraclinoid internal carotid artery was needed in one patient.
      Preservation of the carotid artery was possible in 16 patients. Four patients
      with spontaneous CCFs were advised digital compression of carotid arteries
      resulting in complete closure of the fistula in one and considerable clinical
      improvement in two patients. One patient required transarterial obliteration of
      the fistula via the middle meningeal artery by means of a platinum coil and
      normal butyl cyanoacrylate (NBCA) resulting in total radio anatomical cure.

PMID- 8296530
TI  - H-reflex changes during contractions of the ankle extensors in spastic patients.
AB  - Soleus H-reflexes during tonic contractions and isometric ramp contractions of
      the ankle extensors in spastic and healthy subjects were measured. During the
      tonic contractions, the H-reflex increased with the contraction level. The
      increase was highest in the patients (p < 0.001). The facilitation of the H
      reflex during a ramp contraction is due to a static component resulting from the
      increased excitation level and a dynamic component resulting from the modulation
      of the H-reflex. The dynamic H-reflex facilitation during the ramp contraction
      was decreased in the patients (p < 0.05). The findings suggest that there is a
      decreased H-reflex control in spastic patients and this could be explained by a
      decreased presynaptic inhibition or by postsynaptic changes.

PMID- 8296532
TI  - Diagnosing multiple sclerosis in childhood.
AB  - By presenting the cases of 3 children with laboratory supported definite multiple
      sclerosis [LSDMS] according to Poser's diagnostic criteria, we illustrate the
      difficulties of diagnosing MS in childhood. In search for appropriate diagnostic
      criteria for childhood MS, the literature on childhood MS is reviewed, and the 3
      cases presented are compared with the 15 hitherto reported with the diagnosis
      LSDMS. Specific difficulties of diagnosing MS in childhood are discussed. They
      include history taking in children, the multiple differential diagnostic
      possibilities, and the various clinical presentations. Due to these specific
      difficulties in childhood MS, we conclude that a strict use of Poser's criteria
      is indispensable, especially in childhood MS.

PMID- 8296531
TI  - A double-blind study of L-threonine in patients with spinal spasticity.
AB  - We conducted a double-blind, placebo-controlled, crossover study of oral L
      threonine at 6 g/day in patients with spinal spasticity. Muscle tone from
      selected leg muscles, measured by the Ashworth Scale, was the principal measure
      of spasticity and was evaluated before and at the end of each treatment period. A
      10% reduction in Ashworth score was regarded as a positive response to a
      treatment. The results were analyzed sequentially, patients being classified as
      threonine-responders, placebo-responders or non-responders (those who responded
      to both treatments by either less or greater than 10%) and a level of
      significance of p = 0.05 was chosen. The trial concluded in favour of L-threonine
      after 33 patients. Side-effects were minimal. L-threonine has a modest but
      definite antispastic effect, and its possible role in modifying spinal
      glycinergic transmission is discussed.

PMID- 8296533
TI  - Total reaction time: a new approach in early HIV encephalopathy?
AB  - In an attempt to develop better methods for diagnosis, screening and serial
      assessment of HIV-1-associated cognitive/motor complex, we have added a motor
      component to tests of reaction time, defining the new parameter as total reaction
      time. Thirty-four non-drug-using, HIV-positive men underwent four different tests
      of total reaction time. All four tests reached a level of statistical
      significance, both for a group of patients with early disease and for a group of
      patients with symptoms, compared with a control group. Total reaction time had a
      better discriminatory ability than standard reaction time, particularly for
      patients with early disease. It is suggested that neuropsychological studies of
      HIV-1-associated cognitive/motor complex should include tests of total reaction
      time.

PMID- 8296534
TI  - Symptom progression in Alzheimer's disease: relation to onset age and familial
      aggregation. Results of a longitudinal study.
AB  - We investigated the hypotheses that symptom progression in Alzheimer's disease is
      related to onset age and familial aggregation. In a psychiatric outpatient clinic
      we examined a cohort of 265 consecutively admitted patients 90 of which were
      diagnosed mild to moderate Alzheimer's disease according to the ICD-10 research
      criteria. Within twelve months follow-up 73 cases of these 90 patients were
      investigated twice. We found that early onset cases compared to late onset cases
      as well as patients with a familial aggregation compared to patients without such
      an aggregation were no different with respect to the rate of symptom progression
      in Alzheimer's disease. Furthermore, the hypothesis that early onset cases with a
      familial aggregation more rapidly deteriorate cognitively compared to late onset
      cases without such an aggregation could not be confirmed. Our results suggest
      that the large interindividual variation of symptom progression in Alzheimer's
      disease cannot be explained by onset age and familial aggregation.

PMID- 8296535
TI  - Histologic evidence for a toxic polyneuropathy due to exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) in rats.
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a considerable environmental hazard
      in industrial societies. Its toxic effects on animals and humans are numerous,
      but little is known about its neurotoxicity. We studied the neurotoxic effects of
      TCDD in 80 male, adult Wistar rats. The substance was dissolved in corn oil and a
      single dose injected intraperitoneally (8.8 micrograms, 6.6 micrograms, 4.4
      micrograms or 2.2 micrograms/kg). Neurophysiological examinations proved a dose
      related, statistically significant slowing of sensory and motor conduction
      velocities. Ten months after the application of TCDD peripheral nerves showed a
      progressive, and proximally accentuated neuropathy. The extent of changes,
      however, differed remarkably between individual animals. Our data indicate that
      TCDD caused a toxic polyneuropathy in rats.

PMID- 8296536
TI  - Reduced life expectancy in 40 cases of early onset cerebellar ataxia with
      retained tendon reflexes: a population-based study.
AB  - A survival analysis of 40 cases of early onset cerebellar ataxia (EOCA) with
      retained tendon reflexes was performed. They represent all cases of EOCA
      diagnosed between 1945 and 1990 among residents of a defined area of Northwestern
      Italy, followed up to December 31, 1990. The survival rates were respectively
      92%, 87% and 77% at 10, 20 and 30-years, worse than expected in a disease which
      is usually considered benign. The relative death rate was 4 times higher than
      expected for the general population. Prognosis was significantly worse for males
      than for females, whereas the age of onset and the calendar year of onset did not
      affect survival.

PMID- 8296537
TI  - Ataxia and areflexia in SOAA.
AB  - Fifteen patients with the classical syndrome of ophthalmoplegia, ataxia, and
      tendon areflexia (SOAA) were studied in an attempt to clarify the mechanisms of
      ataxia and myotatic hyporeflexia. All showed features of cerebellar rather than
      sensory ataxia. Peripheral nerve conduction studies, including F-waves, were
      normal in a majority of the patients, as was needle EMG. Low-amplitude compound
      sensory nerve potentials were seen in four patients only, and mild slowing of
      sensory conduction velocity in two. Three had abnormal blink reflex studies,
      suggestive of a central lesion in two, and another two showed a transient delay
      of N5 peak of brainstem auditory evoked potentials. Somatosensory evoked
      potentials were normal. Despite clinically depressed or absent tendon jerks, T
      waves were elicited at normal latencies. These findings do not support the
      prevailing view that the neurological abnormalities in SOAA are due to
      involvement of sensory fibres in the peripheral nerves and dorsal roots. We
      suggest that lesions scattered in the brainstem tegmentum and in the cerebellar
      peduncles are responsible for the ataxia and the depressed tendon jerks.

PMID- 8296538
TI  - Neuropsychiatric and brain CT findings in polycystic lipomembranous
      osteodysplasia with sclerosing leukoencephalopathy.
AB  - Seven patients with polycystic lipomembranous osteodysplasia and sclerosing
      leukoencephalopathy (PLO-SL or membranous lipodystrophy) were examined clinically
      and with CT scanning. The degree of dementia was severe in five cases, marked in
      one case, and mild in one case. All patients suffered from marked or severe
      prefrontal psychosyndrome, impairment of memory and signs of upper motor neuron
      involvement. Epileptic seizures and primitive reflexes were observed in six
      cases. Degree of agnostic-aphasic-apraxic symptoms varied. In all cases CT
      revealed general and diffuse brain atrophy, which was accentuated in frontal
      areas. In the basal ganglia bilateral calcifications (five cases) or a slight
      hyperdensity (two cases) were detected. CT finding in PLO-SL may lead to an early
      diagnosis of this fatal disease.

PMID- 8296539
TI  - Effects of movement-related cortical activities on pain-related somatosensory
      evoked potentials following CO2 laser stimulation in normal subjects.
AB  - We investigated the change in pain perception produced by the application of
      movement and vibration to areas adjacent to, and remote from, the painful
      stimulus. Pain-related somatosensory evoked potentials (pain SEPs) and the pain
      threshold were evaluated following CO2 laser stimulation in 17 normal subjects.
      The concurrent application of vibratory stimuli and the voluntary movement of the
      fingers of the hand to which the pain stimulus was applied significantly reduced
      and prolonged the pain SEPs and increased the pain threshold, consistent with the
      gate control theory. Pain SEPs were also significantly attenuated by voluntary (P
      < 0.001) and passive (P < 0.02) movement of the remote areas such as the foot,
      but the pain threshold was unaffected. This finding was not produced by vibration
      or movement imagery of the limbs without active movement. Therefore, interactions
      between pain perception and movement-related cortical activities must take place
      in some areas of the brain without relieving pain.

PMID- 8296540
TI  - Efficiency of the antihypoxic substance sabeluzole in patients with clinically
      and neurophysiologically evident diabetic polyneuropathy.

PMID- 8296541
TI  - [Facial neurinoma: a possible surprise in the diagnostic approach to Bell's
      palsy].
AB  - A neuroma of the facial nerve is a rather uncommon finding. Two cases of facial
      nerve neuromas, with special focus on the importance of high-definition imaging
      techniques and on the histologic characteristics are presented. Some surgical
      modalities regarding tumor removal as well as facial nerve repair are discussed.

PMID- 8296542
TI  - [The use of glass ionomer cement in otology and in otoneurosurgery].
AB  - The use of glass ionomer cement for mastoid obliteration, reconstruction of the
      external ear canal, closure of the translabyrinthine approach for acoustic
      neuroma and fixation of a cochlear implant in the temporal bone is described.
      Preliminary results are encouraging, although some epithelialisation defects may
      occur in the external ear canal.

PMID- 8296543
TI  - The contralateral ear after surgery in different otoneurosurgical or
      neurosurgical pathologies.
AB  - The present study was specifically designed to ascertain the effect that
      otoneurosurgical or neurosurgical approaches may have on the contralateral ear.
      18 patients suffering from different histologic lesions were examined. Pure-tone
      audiometry was performed before and after surgery each postoperative day up to
      the fourteenth day. The audiograms were abnormal after surgery in all but one of
      the patients tested. This hearing loss was transitory and the recovery occurred
      completely within 3 months. These outcomes suggest that the hearing loss was
      linked to a loss of cerebrospinal fluid.

PMID- 8296545
TI  - [Giant cementifying fibroma of the maxillary sinus. Apropos of a case].

PMID- 8296544
TI  - [Etiology and fate of true perilymphatic fistulae].
AB  - Perilymphatic fistulas of the round or oval window in a traumatic context or
      following middle ear surgery or pathology, are reported. Rapid surgical
      exploration secures the best clinical results.

PMID- 8296546
TI  - [Functional endoscopic sinus surgery. Evaluation methods and results].
AB  - Functional Endoscopic Sinus Surgery (FESS) is now undoubtedly the choice
      procedure for the surgical treatment of chronic sinusitis and nasal polyposis
      after failure of medical treatment. Between January 1990 and December 1992, 51
      patients with chronic sinusitis and 44 with nasal polyposis who underwent FESS
      were evaluated (170 ethmoidectomies). Preoperative evaluation is obtained through
      personal scaling combined with a CT of the sinuses, whereas postoperative
      assessment is based on the same scoring together with an endoscopic evaluation.
      Good functional results and no significant differences between the two types of
      pathology are obtained after a 1 year follow-up.

PMID- 8296547
TI  - [Differential diagnosis of nasopharyngeal masses in adolescents. Apropos of a
      case of antrochoanal polyps].
AB  - A case report of an antrochoanal polyp originating in the frontal sinus of a 14
      year old boy is presented. This condition is very rare. The differential
      diagnosis is reviewed.

PMID- 8296548
TI  - [Frontal mucocele. Clinical symptoms, treatment and results apropos of 17 cases].
AB  - The ophthalmological signs are stressed in the management of frontal mucoceles.
      The authors report good results of their surgical technique with bicoronal
      approach, exenteration of the pathology and complete obliteration of the frontal
      sinus by bone chips.

PMID- 8296549
TI  - [Nasal endoscopic treatment of a CSF fistula. Clinical case].
AB  - A patient presenting a recent spontaneous C.S.F. leak was endoscopically treated.
      Several materials were used to seal off the fistula. The literature on the
      etiology and treatment of C.S.F. leaks is presented.

PMID- 8296550
TI  - Surgical or medical treatment of questionable peritonsillar abscess? The use of B
      mode ultrasonography.
AB  - A prospective study was carried out to evaluate the sensitivity of sonography in
      the diagnosis of peritonsillar abscesses (quinsy). From 1986 to 1991 all cases of
      clinically doubtful peritonsillitis were subjected to B-Mode ultrasonography of
      the tonsils before tonsillectomy. 118 patients were examined. Sensitivity of the
      method in cases of clinically uncertain peritonsillar abscesses was 87%. The
      predictive value of the method was calculated to be 0.89; however only five false
      positive cases ("abscess" in ultrasound but no pus during surgery) were found. We
      therefore suggest that all patients suffering from questionable peritonsillitis
      should be examined by ultrasound. If abscess formation is suspected, surgical
      intervention is indicated. In all other cases I.V. antibiotics should be
      administered and control sonography should be carried out.

PMID- 8296551
TI  - The problem of lower respiratory tract foreign bodies in children.
AB  - The authors treat the problem of lower respiratory tract foreign bodies in
      children on the basis of their own longterm experience. In the years 1972-1991 in
      the Pediatric E.N.T. Clinic of the Pediatric Institute, Academy of Medicine in
      Poznan, 147 foreign bodies were removed. A positive history of foreign body
      aspiration was obtained in 45.7% of the cases. 44.7% of the foreign bodies were
      removed during the first 24 hours after their aspiration. Broncho-pulmonary
      complications occurred in 59.1% of the cases.

PMID- 8296552
TI  - [Neurinoma of the cervical vagus nerve. Apropos of a case--literature review].
AB  - A rare case of a high cervical mass bulging in the hypopharynx is reported. The
      clinical and radiological characteristics of these tumours are described and a
      review of the literature is included.

PMID- 8296553
TI  - Enteral nutrition following total laryngectomy.
AB  - Body composition was measured in patients who underwent total laryngectomy for
      carcinoma and who were enterally fed throughout the postoperative period with
      full liquid artificial mixtures. The intestinal complications were very mild and
      required no changes in the nutritional program. Body sector sizes remained
      essentially unchanged until the end of the support, malnutrition did not occur
      and the postoperative local infection rate was very low. On the contrary, in
      patients fed with blenderized food, the amount of enteral infusion had to be
      reduced because of poor tolerance or abdominal discomfort; in this case caloric
      intake was largely inadequate. Fall in BW and BCM size and increase of TBNa/TBK
      ratio demonstrated a postoperative impairment of the nutritional status.
      Furthermore, the postoperative infection rate, the number of days with fever and
      the length of antibioticotherapy were higher than those observed in patients fed
      with full liquid mixtures.

PMID- 8296554
TI  - Gastrointestinal perforation in infants: cases unrelated to necrotizing
      enterocolitis.
AB  - From January 1984 to March 1992, there were 19 infants admitted to our hospital
      with gastrointestinal perforation not associated with necrotizing enterocolitis.
      Seven patients (37%) were premature. Six patients (32%) had their perforations
      located in the stomach, 9 (47%) in the small intestine, and 3 (16%) in the colon.
      The most common clinical presentation was abdominal distention (95%).
      Pneumoperitoneum was noted only in 12 (63%) patients. About 60% of the patients
      had the perforation occur before 4 days of age. The predominant cause of
      perforation was unknown, so called spontaneous perforation (8/19, 42%), followed
      by ischemia or infarction (5/19, 26%). The overall mortality rate was 32%. The
      non-survivors had more severe metabolic acidosis than the survivors, but there
      were no differences in the birthweight and gestational ages of these two groups.
      Sepsis accounted for 83% of the deaths. Early diagnosis and treatment are the
      best ways to promote survival.

PMID- 8296555
TI  - Fungal esophagitis in children.
AB  - Seven patients were endoscopically diagnosed as having a fungal esophagitis with
      mycologic or histologic support for the diagnosis from 1979 to 1991 in the
      Department of Pediatrics, National Taiwan University Hospital. The major
      causative agent was Candida albicans. Other fungi isolated were Candida Krusei,
      Trichosporon cutaneum, Trichosporon beigelii, and Rhodotorula rubra, but they all
      resembled one another under endoscopic examination. The most common presenting
      symptom was hematemesis, and the lower part of the esophagus was more often
      involved. Only one patient was documented to have oral thrush. Most of the
      children did not present typical symptoms of esophagitis such as dysphagia or
      odynophagia, and they tended to be in more advanced stages of the disease when
      the diagnosis was made.

PMID- 8296556
TI  - Postnatal growth of low birthweight neonates in Taiwan.
AB  - The postnatal growth pattern of four hundred and twenty five Chinese low birth
      weight neonates was assessed. All those whose birthweight were below 2500 grams
      and survived for more than 180 days during the study period were included. The
      gestational age was between 26 and 40 weeks, and the birthweights were between
      766 and 2496 grams, respectively. Infants were grouped according to 250-gram
      birth-weight categories. The mean age of the lowest weight, mean age of weight
      regain, and percentage of weight loss were calculated for each weight group and
      demonstrated an inverse correlation to the birthweight. The mean age of the
      lowest weight ranged between 2.72 and 6.62 days, mean weight loss was between
      4.06 and 14.56%, and age of weight regain was between 4.93 and 17.15 days,
      respectively.

PMID- 8296557
TI  - Benign seizures associated with mild diarrhea: clinical analysis of 20 cases.
AB  - Even without electrolyte imbalance, dehydration and fever, seizures are found
      occasionally in the cases of mild diarrhea. Such patients have shown favorable
      outcome during long-term follow-up. Twenty cases (10 boys and 10 girls) of benign
      seizure with mild diarrhea have been diagnosed at the Pediatric Department of
      Cathay General Hospital from January 1987 to March 1991. Ages-of-onset ranged
      from 3 months to 43 months (mean 19 months). Most cases were found between
      December and March (16 cases, 80%). Most seizure episodes were from 2 to 5 times
      (10 cases, 50%); the durations of seizures were mostly within a 5-minute period
      (16 cases, 80%). All seizures were generalized and symmetric, including tonic
      clonic (13 cases, 65%), tonic (5 cases, 25%), and clonic (2 cases, 10%). Six out
      of 11 cases (54.5%) showed Rotazyme (Latex agglutination) positive. After six
      month to four year follow up, no patient had suffered any type of epilepsy, and
      psychomotor development was normal in all. Further discussion of clinical
      features is provided.

PMID- 8296558
TI  - [Neonatal hearing screening].
AB  - Auditory deprivation in early life significantly effects speech, language,
      cognition and learning development. The importance of neonatal hearing screening
      in order to detect and manage children with hearing impairment during the
      critical period before three years of age can't be neglected. The neonatal
      hearing screening program at Veterans General Hospital, Taipei, under a
      cooperation of audiologists, otologists and pediatricians, identified 1885
      neonates for hearing loss from September 1990 to August 1991. There were two
      study groups, a high risk group of hearing impairment and a non-high risk group.
      We performed hearing screening and followed-up for the failure at initial test
      using methods including behavioral observation audiometry, auditory brainstem
      response, tympanogram, pneumatic otoscopy and questionnaire. Approximately 2.7%
      of neonates were classified as high risk for hearing loss, the incidence of
      hearing loss was 8% to 14% in this group. The incidence of hearing loss in non
      high risk group was 0.11%. If both groups were contained that the incidence of
      hearing loss was 0.32% to 0.48%, 0.11% with a sensorineural hearing loss, 0.21%
      to 0.37% with a conductive hearing loss. Both behavioral audiometry (89% false
      negative rate) and questionnaire (50% return rate) were not effective for
      screening purposes in this study. Our results also indicated that the most
      advantage of using a high risk register lay in the fact that only 2.7% of a total
      population needed to be screened to identify approximately 67% to 78% of hearing
      impaired babies. This saved both time and money.

PMID- 8296559
TI  - Severe hypertension in hypoplastic kidney and bilateral renal artery stenosis:
      report of one case.
AB  - A three year-old boy was found incidentally to have severe hypertension (around
      200/110 mmHg) when he was brought to This Hospital's Emergency Department because
      of his abdominal pain. After his admission, serial and detailed examinations were
      performed. These included: basic blood chemistry studies, abdominal and renal
      sonography, excretory urography, radionuclide scintigraphy and angiography with
      selective renal vein renin sampling. Diagnosis was made of renovascular
      hypertension with combination of unilateral renal hypoplasia and bilateral renal
      artery stenosis. The patient was given oral anti-hypertensive drugs, with
      resulting satisfactorily controlled blood pressure after two weeks of treatment.
      He was discharged without surgical intervention.

PMID- 8296560
TI  - Multicystic encephalomalacia in a surviving monochorionic twin.
AB  - From a recent monochorionic diamniotic twin pregnancy seen at this hospital, one
      of the twins died in utero at 37 weeks' gestation. The other twin, a male infant,
      was delivered by Cesarean section because of fetal distress, with resuscitation
      performed in the delivery room. The infant developed generalized tonic seizure
      shortly after stabilization, and was put on anticonvulsants. The initial brain
      echography was normal; follow-up echograms and CT scans performed at 8 and 12
      days old, respectively, revealed diffuse low density over both side of cerebral
      hemisphere. At one month old, the infants's brain echogram showed diffuse cystic
      encephalomalacia. At four months, he was noted to be spastic and significantly
      delayed in neurodevelopment. Disseminated intravascular coagulation caused by
      fetal-to-fetal transfer of thromboplastic material from the dead fetus was
      considered as the most possible cause of the neurological complication in this
      patient. In addition, perinatal hypoxic-ischemic insult may also have been a
      superimposed, influencing factor.

PMID- 8296561
TI  - Congenital ovarian cyst: report of one case.
AB  - The detection rate of ovarian cyst in neonates has been increased through use of
      prenatal and postnatal ultrasonography. A term female neonate, born to a G1P1
      healthy mother, was found to have a cystic mass at the upper pole of the right
      kidney through prenatal sonographic evaluation. The cyst was also demonstrated to
      be located in the right pelvis by CT scan after birth. Because of the apparent
      floating nature of the cyst, laparotomy was performed at the age of seven days. A
      4x3x3 cm3 cyst was found in the right ovary. Pathological examination of the cyst
      revealed a follicular cyst. The thyroid function was also checked before
      operation and revealed normal.

PMID- 8296562
TI  - Pulmonary artery sling with tracheo-bronchial stenosis: report of one case.
AB  - This patient is a 6-month-old female baby with intermittent symptoms of air-way
      obstruction for two months. The diagnostic examinations performed included:
      esophagogram, two-dimensional echocardiography, cardiac catheterization with
      selective right pulmonary arteriography, magnetic resonance imaging (MRI) and
      tracheo-bronchogram. The esophagogram revealed anterior indentation of the
      esophagus. The echocardiogram, cardiac catheterization and MRI all demonstrated
      anomalous origin of the left pulmonary artery from the right pulmonary artery
      instead of the main pulmonary artery. The tracheo-bronchogram showed long-segment
      stenosis of the lower portion of the trachea. A final diagnosis of pulmonary
      artery sling with tracheo-bronchial stenosis was made. Since the parents refused
      surgery, the baby expired after several episodes of cyanosis & cardiac arrest.

PMID- 8296563
TI  - Fatal enteroviral infection in a neonate.
AB  - Enterovirus infection has been recognized as one of the most common viral
      infections in the perinatal and neonatal periods. It frequently leads to
      significant mortality. One fatal case of neonatal enteroviral infection was
      experienced in last year. The patient was a one-day-old male, presenting with
      neonatal sepsis. He has a biphasic illness, first with a mild febrile prodrome
      then followed by severe systemic involvement, with meningitis, myocarditis,
      hepatosplenomegaly and disseminated intravascular coagulation. All bacterial
      cultures were negative, but the rectal swab isolated enterovirus. The
      echocardiogram revealed depressed cardiac function, and he finally expired at the
      age of 10 days. The autopsy findings supported the diagnosis of perinatal
      enteroviral infection (coxsackievirus B infection was highly suspected).
      Clinically, if a neonate presents as sepsis, but has the following conditions,
      enteroviral infection should be considered: (1) negative bacterial cultures; (2)
      multiple organ involvement; (3) proven enteroviral infection in the same nursery
      or ward; (4) a mild febrile illness in the mother within the last antepartum 10
      days or the first postpartum 5 days; (5) any family members with fever or signs
      of upper respiratory infection within 15 days before delivery.

PMID- 8296564
TI  - [Science, bioethics, bionomy: a transdisciplinary program].

PMID- 8296565
TI  - [Psychology training in Latin America].
AB  - Although there is not such a thing as a sole criterion to define the origins of
      Psychology as an autonomous discipline, it is the author's contention that the
      roots for such an autonomy are to be found in the emergence of professional
      psychologists in the USA by the turn of the 19th century. Latin America has based
      its academic courses on the utilitarian, professionally-oriented American pattern
      considering, however, European sources for designing curricula. Latin American
      countries with a higher development level such as Mexico, Colombia, and Brazil
      are endowed with an excellent level as regards both their advancements in
      research, and legal achievements. Despite the different national traits, Latin
      American Psychology as a whole shares common features such as: its being
      originated in Humanities Departments at universities, its evolution from
      Psychometrics to the fostering of human resources, and its struggles so that it
      could eventually be differentiated from other professions. It is rather difficult
      to issue reliable predictions for the time being since quite heterogeneous social
      as well as historical factors bear on Latin American science and Latin American
      professionals alike.

PMID- 8296566
TI  - [Death. Euthanasia].
AB  - In this life of ours, the most important thing is life itself--even though this
      sounds like a truism. However, perspectives differ when it comes to evaluating
      life; that is, what are we able and willing to "pay" just for keeping it? Without
      mentioning that risking one's own life may be a source of profit. At times.
      Besides, other people's life is appraised according to different criteria: Some
      circumstances suggest that disposing of others' life--i.e. eliminating it good
      and proper--is advisable. Whenever such a decision is made, apparently for the
      sick person's own good, the physician in charge must go in for it. In such cases,
      the conditioning factors of a physician's behavior are questionable. Brain death,
      for instance, is a good example.

PMID- 8296567
TI  - [Psychoactive substance abuse. Basis for a regional epidemiologic surveillance
      system].
AB  - A profile of alcohol and drug abusers in many a Latin American country features
      large groups with no or insufficient access to health services. In the light of
      such a situation, health resources should focus their efforts on addressing the
      effects instead of the causes of the problem. Both developing and strengthening
      local health systems should be a part of the overall effort. Every regional
      epidemiologic surveillance system must be decentralized, taking into account
      social participation, local limitations, as well as health personnel training.
      Placing an emphasis on research as an instrument for action is crucial for Latin
      America.

PMID- 8296568
TI  - [Sociodemographic and clinical characteristics of women who attempted suicide].
AB  - Sociodemographic and clinical features of 124 female suicide attempters, referred
      to the psychiatric unit of a general hospital have been assessed by means of
      semistructured interviews, and Pierce's Suicide Intent Scale. Mean age was 30.8
      +/- 9.8 years. Subjects' socioeconomic and educational status were low. Attempts
      were impulsive in 70%, the most frequent method subjects resorted to was overdose
      (68%). Most common causes for the attempt were difficulties with either marital
      life or relatives. The attempt was assessed as severe in 45% of cases. Previous
      attempts were found in 56%. At assessment, 50% of subjects were with Major
      Depression (DMS-III-R). Subjects with recurrent depressive disorders evidenced a
      significantly higher rate of severe attempts, and previous suicidal episodes.
      Findings reported herein are relevant to a secondary prevention of suicidal
      behavior.

PMID- 8296569
TI  - [Patients cared for at the mental health unit of a primary care office: morbidity
      study].
AB  - Establishing the frequency of mental disorders among patients cared for at the
      mental health unit of a primary care outpatient clinic of Santiago, Chile, is
      intended. In this connection, 618 medical records have been screened
      retrospectively (i.e. a whole universe excepting patients under age 15). A great
      majority of patients--with an absolute ratio of female patients (88.8%) were
      referrals from physicians' offices. The most frequent disorders were anxiety
      disorders and adjustment disorders. Comments are made on (a): the scarcity of
      referrals from larger general hospitals, and (b) the need for mechanisms apt at
      an early detection of the most frequent disorders to be set up.

PMID- 8296570
TI  - [Overweight and obesity in Chilean women. A multivariate characterization based
      on psychophysiologic indicators].
AB  - This paper presents a reanalysis of previously collected data using multivariate
      statistical methods. Aside from confirming the discrimination between obese, and
      normal-weight women through psychometric indicators including a personality
      evaluation, and a verbal affective expression assessment, the power of
      multivariate methods for improving diagnosis is illustrated.

PMID- 8296571
TI  - [A methodological contribution to the knowledge on psychosocial alienation].
AB  - A methodological approach to the study of alienation at a psychological level is
      discussed. Owing to the methodological purpose of the research at stake,
      researchers paid attention to the fact that the questionnaire items had been
      written in the first person singular--a fact that encouraged researchers to work
      anew, on the hypothesis of the personal implication of subjects with the items
      contents. A conclusion was thus reached that an item written in first person
      singular dissuades subjects from telling what they think or feel actually,
      inducing subjects to produce social desirability-oriented answers.

PMID- 8296572
TI  - [San Hipolito and the Divino Salvador: the first psychiatric hospitals in
      America].

PMID- 8296573
TI  - Reliability of a standardized and expanded Brief Psychiatric Rating Scale: a
      replication study.
AB  - This study aimed to determine the replicability of the interrater reliability
      coefficients obtained with a standardized and expanded Brief Psychiatric Rating
      Scale (BPRS-E) in a 1991 psychometric evaluation. Furthermore, intrarater
      reliability was assessed. At item level, interrater concordance turned out to be
      satisfactory for most of the BPRS-E items. However, only a few of the items
      reached acceptable chance-corrected coefficients. In contrast to the previous
      study, the anxiety-depression subscale met the standard of acceptable interrater
      reliability in the present study. As in the 1991 study, the 10-item psychotic
      disintegration scale as well as BPRS-18 global scores met (or closely
      approximated) this standard. The 6 additional items of BPRS-E did not contribute
      to the scale's reliability. Joining the samples of the 1991 and replication
      studies (to cover the range of symptoms' severity and heterogeneity more fully)
      did not improve interrater reliability. Intrarater reliability coefficients were
      globally comparable to interrater reliability coefficients. In all, the results
      of this replication study suggest that only the anxiety-depression subscale, the
      10-item psychotic disintegration scale and the BPRS-18 global scale can be used
      reliably in unselected groups of psychiatric inpatients in acute distress.

PMID- 8296574
TI  - Comparison of four diagnostic systems for the diagnosis of somatization disorder.
AB  - This article compares the Feighner criteria, the DSM-III criteria for
      somatization disorder and a modified version of the proposed ICD-10 criteria.
      Working with a data set collected from the charts of 250 patients considered
      likely to have unexplained somatic symptoms, the kappa statistic and percentage
      agreement was calculated. The kappa between the DSM-III and DSM-III-R criteria is
      0.93. Between the modified ICD-10 and DSM-III it was 0.71, but between Feighner
      and the modified ICD-10 it was 0.44. However, the different criteria identify the
      same patient population based on mental co-morbidity and demographics. The
      authors suggest that the modified version of the proposed ICD-10 should be
      investigated further, as it can use data sets previously collected for
      assessments of somatization disorder.

PMID- 8296575
TI  - Personality traits and disorders among transsexuals.
AB  - A group of transsexuals, 9 biological men and 10 women, was assessed according to
      clinical DSM-III-R diagnosis and a self-report instrument for Axis II diagnoses
      based on the Structured Clinical Interview for DSM-III-R (SCID screen). A control
      group of 133 individuals was assessed by the same instrument. Combined with a
      functional criterion according to the Global Assessment of Functioning, the SCID
      screen showed good agreement with clinical Axis II diagnoses. The overall
      proportion of Axis II criteria fulfilled, proportion of criteria fulfilled for
      every single personality disorder and number of personality disorders were
      calculated from the modified version of the SCID screen. Personality disorders,
      mainly within cluster B, were identified among 5 of 19 transsexuals, and a
      majority had multiple personality disorders. Among controls, no personality
      disorder was identified. Personality traits as measured by the SCID screen
      revealed significantly more subthreshold pathology among transsexuals than
      controls in 8 of 12 personality categories. The proportion of overall Axis II
      criteria fulfilled was 29% among transsexuals versus 17% among controls. Sex
      differences among transsexuals, the usefulness of the SCID screen and diagnostic
      problems in DSM-III-R with respect to gender identity disorders are discussed.

PMID- 8296576
TI  - Does prenatal influenza divert susceptible females from later affective psychosis
      to schizophrenia?
AB  - We examined the relationship between influenza epidemics and the number of
      schizophrenic and affective psychotic individuals born each month between 1938
      and 1965 in England and Wales. Increased death rates from influenza were followed
      5 months later by a significant increase in schizophrenic births and a concurrent
      fall in the number of births of affective psychotic individuals. When the sexes
      were examined separately, both the positive effect of influenza on schizophrenic
      births and its negative effect on affective psychotic births were evident for
      females but not for males. Furthermore, during February to June in high influenza
      years, there was an inverse relationship between the number of female
      schizophrenic and affective psychotic births. The explanation for these
      surprising findings may be that prenatal exposure to influenza impairs the
      neurodevelopment of some females with a predisposition to affective psychosis, in
      such a way that their later illness shows schizophrenic rather than affective
      features.

PMID- 8296577
TI  - Electrodermal activity in anxiety disorders.
AB  - Forty anxiety patients diagnosed according to DSM-III-R criteria were included:
      panic disorder (n = 12), agoraphobia (n = 11), generalized anxiety disorder (n =
      9), anxiety disorder not otherwise specified (n = 8) and compared with 12
      controls. Millon Clinical Multiaxial Inventory and Symptom Checklist-90R symptom
      and personality scales did not separate the diagnostic groups. Electrodermal
      activity showed delayed habituation and high spontaneous skin resistance
      fluctuations in the panic and agoraphobia groups compared with the non-panic
      groups. The generalized anxiety disorder patients could not be separated from the
      controls, and the anxiety disorder not otherwise specified patients showed less
      electrodermal activity than the controls on most variables. In contrast to self
      report instruments, electrodermal activity discriminated between diagnostic
      groups of patients with DSM-III-R anxiety disorders, more specifically between
      patients with and without panic attacks.

PMID- 8296578
TI  - Changes in the frequency distribution pattern of body weight in patients with
      major depression.
AB  - To compare the frequency distribution of body weight of the depressed patients
      with that of a standard group and to evaluate the change in distribution during
      treatment, body weight was measured in 106 depressed inpatients with major
      depressive disorder as defined by DSM-III criteria both on admission and on
      discharge. The body weight distribution in the depressed patients skewed towards
      a high frequency of lower weights on admission but shifted to the normal pattern
      on discharge. In women, this tendency was more obvious and was statistically
      significant. The body weight distribution in the depressed patients with
      melancholia maintained high frequencies of lower body weight on discharge, while
      that in those without melancholia did not, suggesting that there could be a
      difference in the pattern of body weight distributions between those with
      endogenous and nonendogenous depression. Three tricyclic antidepressants examined
      (imipramine, clomipramine and desipramine) did not seem to have the side effect
      of pathological weight gain in the frequency distribution pattern.

PMID- 8296579
TI  - Assessing atypical seasonal affective disorder complaints by means of self
      rating.
AB  - The atypical complaints of Seasonal Affective Disorder (SAD) are usually assessed
      clinically by means of 7 questions added to the Hamilton Rating Scale for
      Depression (HRSDadd). In this study, these complaints were assessed by means of
      relevant and modified items of the Beck Depression Inventory (BDIadd), a self
      rating instrument. A highly significant correlation between the two assessment
      procedures was found. This suggests that the BDIadd is a very useful alternative
      to the HRSDadd.

PMID- 8296580
TI  - The impact of availability, attraction and lethality of suicide methods on
      suicide rates in Germany.
AB  - Substantial fluctuations have prevailed in both the rate and particular methods
      of suicide in the Federal Republic of Germany during the past 40 years. The
      current study examines the extent to which the availability, attraction and
      lethality of particular methods of suicide affect suicide rates. A close
      relationship existed in the period from 1949 and 1989 between the peaks of the
      suicide rate and the percentage of low threshold suicide methods according to De
      Catanzaro, whereby suicide in this context is understood to mean suicide by
      shooting or intake of solid, liquid or gaseous poisons. Our hypothetically
      expected lesser compensation between high and low threshold methods for women was
      confirmed. Between 1963 and 1976 the rate of suicide committed using domestic gas
      receded dramatically. Within the same period, however, the rate of suicide
      committed using other poisons rose accordingly.

PMID- 8296581
TI  - Prospective evaluation of the serotonin syndrome in depressed inpatients treated
      with clomipramine.
AB  - The serotonin syndrome, induced by serotoninergic agents, includes confusion,
      agitation, myoclonus, diaphoresis, tremor and diarrhea. The authors prospectively
      evaluated all these symptoms in 38 depressed inpatients fullfilling DSM-III-R
      criteria for major depression. Sixteen (42%) of 38 patients presented at least
      one symptom of serotonin syndrome. In 14 cases tremor and myoclonus occurred
      simultaneously, and 10 patients presented at the same time tremor plus myoclonus,
      diaphoresis and shivering. Except for 2 patients, symptoms were transient, lasted
      less than 1 week and disappeared with the pursuit of treatment.

PMID- 8296582
TI  - Treatment of winter depression in Norway. II. A comparison of the selective
      monoamine oxidase A inhibitor moclobemide and placebo.
AB  - Thirty-four patients with seasonal affective disorder, winter depression type
      (WD) were randomly distributed to receive the selective monoamine oxidase-A
      inhibitor moclobemide (400 mg daily) or placebo in a double-blind, parallel group
      study lasting for up to 14 weeks. Severity measures were the Montgomery-Asberg
      Depression Rating Scale (MADRS) extended with characteristic symptoms of WD;
      summed score of the "atypical" symptoms hypersomnia, hyperphagia and carbohydrate
      craving; and Clinical Global Impressions (CGI). After 3 weeks, patients with
      unsatisfactory response were switched to open moclobemide. Three patients on
      placebo dropped out before 3 weeks. Extended MADRS and CGI showed no significant
      difference between the groups at 3 weeks, whereas the atypical score was reduced
      significantly more on moclobemide than on placebo already after one week.
      Nonresponders after 3 weeks (9 of 16 on moclobemide and 7 of 15 on placebo)
      improved rapidly after being given open moclobemide. Predictor analysis showed a
      remarkably high negative correlation between improvement at 3 weeks (extended
      MADRS) and age in the placebo group and a strong, nonsignificant trend in the
      same direction in the moclobemide group. Dichotomizing the patients according to
      the median age (45 years) resulted in a somewhat better effect of moclobemide
      than placebo in the older age group. There were no significant differences in
      side effects between moclobemide and placebo.

PMID- 8296583
TI  - CQI as a research focus.

PMID- 8296584
TI  - Collaborating with nonphysician professionals in practice-based research.
      Dizziness Research Group.
AB  - Although much has been written about the importance of collaboration among
      physicians in practice-based research, the relationship between the clinical
      investigator and nonphysician professionals in this setting has received less
      attention. Nurses, physician assistants, and other office support staff can
      provide valuable insights pertinent to research design and project
      implementation. Because nonphysician professionals frequently play a large part
      in implementing a research project, how well the investigator collaborates with
      them often determines the success or failure of the project. We suggest the
      following guidelines: 1. Consider the research interests of the nonphysician
      collaborators. 2. Adapt the project to office routine. 3. Limit the demands on
      staff. 4. Use detailed protocols. 5. Orient all collaborators. 6. Be available
      and visible. 7. Provide feedback and reward to all collaborators.

PMID- 8296585
TI  - Immunization barriers in Minnesota private practices: the influence of economics
      and training on vaccine timing.
AB  - OBJECTIVE: Identify barriers to immunization and evaluate the timing of
      immunization in private practice settings. METHODS: Design was a comparison of
      childhood immunization data with a survey of physicians who administered the
      vaccines. Setting was primary care offices in rural and urban/suburban Minnesota.
      Subjects were children under 7 years old who were receiving either Diphtheria,
      Tetanus, and Pertussis vaccine, Diphtheria and Tetanus vaccine, or the first
      Measles, Mumps and Rubella vaccine and their primary care physicians. Main
      outcome measures were time from birth to the third Diphtheria, Tetanus, and
      Pertussis vaccine (DTP) and from birth to the first Measles, Mumps, and Rubella
      vaccine (MMR) and their determinants. RESULTS: The third Diphtheria, Tetanus, and
      Pertussis vaccine and first Measles, Mumps, and Rubella vaccine were late in 32%
      and 41% of children, respectively. We observed a significant difference, based
      upon insurance status, in Diphtheria, Tetanus, and Pertussis vaccine timing (p =
      0.0001) but not in Measles, Mumps, and Rubella vaccine timing. Significant
      correlates of earlier Diphtheria, Tetanus, and Pertussis immunization include
      physician residency training, suburban/urban practice locale, and the likelihood
      that the physician would refer children based upon insurance coverage to health
      departments for immunization. CONCLUSIONS: Important determinants of immunization
      in the private sector include reimbursement and physician training about
      prevention.

PMID- 8296586
TI  - Hypertension management: relationship between visit interval and control.
AB  - OBJECTIVE: Hypertension is one of the most common diagnoses resulting in an
      office visit to the physician. We examined the relationship between the variation
      in the interval between follow-up visits for hypertensive patients and the
      control of blood pressure. METHODS: The sample consisted of 113 patients who made
      399 visits. Data included current medical problems, medications, type of health
      insurance, and socioeconomic status for each patient. RESULTS: The mean number of
      days between visits was 70.6 with a standard deviation of 76.3. No significant
      relationship was found between visit interval and severity of hypertension (p =
      0.14). Sample size made it possible to detect a 20% difference with a likelihood
      of 0.80 at a significance level of 0.05. CONCLUSIONS: Our findings are limited by
      our focus on patient behavior rather than physician recommendation concerning the
      interval between visits, and by the distinct possibility that many of the visits
      were made for reasons other than follow-up of hypertension.

PMID- 8296587
TI  - Predicting atypical Pap smear progression: a case-control study.
AB  - OBJECTIVE: This case-control study proposed to define risk factors for
      progression of cervical disease beyond an atypical level, and to explore the
      possibility of a clinical tool that would aid the clinician in deciding on the
      need for colposcopy. METHODS: Twenty-three hundred (2,300) abnormal Papanicolaou
      smears were reviewed to identify documented cases of class II Papanicolaou smears
      that had progressed. Controls were randomly chosen for each case from the
      remaining pool of available class II Papanicolaou smears that did not progress.
      Data analyses were conducted to determine the predictive value of information
      that would be in a patient's chart with respect to progression from class II
      Papanicolaou smear to a higher level of disease. RESULTS: A univariate analysis
      revealed several significant variables, including age, education, attendance at a
      public clinic, marital status, notification of Papanicolaou results, and a
      history of sexually transmitted disease. Next, a multivariate analysis
      demonstrated that a group of significant variables could not be defined, and only
      notification of an atypical Papanicolaou smear was significant. CONCLUSIONS: The
      study's findings suggest that the data available in a patient's medical record
      are not sufficient to develop a risk assessment scale and provide evidence of the
      need for continued study in this area.

PMID- 8296588
TI  - Psychosocial performance of family physicians.
AB  - This study surveyed 30 residency-trained family physicians all currently in
      practice to determine the nature of their psychosocial interactions with
      patients. In general, respondents were satisfied with the quality of their
      psychosocial training in residency and generally evaluated their competency on a
      range of psychosocial skills as adequate to excellent. Physician psychosocial
      competency was most strongly related to residency, but not to postresidency,
      behavioral science training or to psychosocial screening practices. Frequency of
      performing psychosocial behaviors was also related to behavioral science
      training, as well as to length of time in practice. Neither frequency nor self
      perceived competency related to physician age, gender, patient volume, or type of
      practice.

PMID- 8296589
TI  - Epidural analgesia for labor in a community hospital.
AB  - Epidural analgesia offers excellent relief from the pain of uterine contractions
      during labor. It is well tolerated by both mother and baby. However, recent
      reports suggest that epidurals increase the rate of both cesarean sections and
      instrumental deliveries, with their attendant costs and morbidities. At our
      community hospital, 100 consecutive labors using epidural anesthetics were
      contrasted with 100 consecutive labors managed without them. No significant
      differences were found in birth weights, Apgar scores, cesarean section rate, or
      complications. Forceps use was greatly increased, from 13% to 37% (p < 0.01).

PMID- 8296590
TI  - Physician attitudes toward the Bethesda System of reporting cervical cytology.
AB  - OBJECTIVE: The purpose of this investigation was to determine family physicians'
      and gynecologists' attitudes toward and understanding of the Bethesda System, a
      new cervical cytology classification and reporting system. METHODS: A convenience
      sample of 159 family physicians and gynecologists completed a questionnaire that
      assessed attitudes, knowledge, and opinions about the Bethesda System. RESULTS:
      Compared with family physicians, gynecologists thought the Bethesda System was
      more likely to cause patient management problems (p < 0.001) and preferred not to
      combine viral cytologic effects with mild dysplasia when reporting a low-grade
      squamous intraepithelial lesion (p < 0.004). However, increased understanding of
      the system by physicians correlated with greater preference for the Bethesda
      System (p < 0.02). In this exploratory study, family physicians, rather than
      gynecologists, were more inclined to use the Bethesda System and perceived it as
      a means to reduce clinical evaluation and patient management problems.
      Gynecologists reported a fuller understanding of the Bethesda System, yet they
      were more critical of the cytology categorizations. Within each specialty,
      greater understanding of the Bethesda System led to its wider acceptance.

PMID- 8296591
TI  - Informational yield of comprehensive Geriatric Home Assessment.
AB  - OBJECTIVE: The purpose of this study was to compare the relative informational
      yield of Geriatric Home Assessments with medical charts of patients seen in
      family practice settings. METHODS: The information from comprehensive Geriatric
      Home Assessments of 28 well-established patients, conducted by small groups of
      medical students in a family practice clerkship, was compared with information
      available in the medical charts of these patients for the previous three years.
      RESULTS: For no problem studied was identification in the medical chart as high
      as from the Geriatric Home Assessment. Problems with family/social support,
      inadequate dental care, and immunization deficiencies were frequently noted in
      the Geriatric Home Assessment but only rarely in the medical chart. Concordance
      between Geriatric Home Assessment and medical charts was greatest for
      depression/anxiety, sensory loss, smoking, dizziness, and sleep problems.
      CONCLUSIONS: While evaluation of the utilization of information was beyond the
      scope of the current study, the results suggest the potential usefulness of
      complementing office care with home assessments in establishing a data base for
      the medical management of elderly patients in primary care settings.

PMID- 8296592
TI  - Resource use by younger versus older patients.
AB  - OBJECTIVE: Compared to younger persons, the elderly use disproportionately
      greater health care resources. We wondered if this difference persisted when care
      of both older and younger patients was managed by physicians of a single
      specialty, family practice. METHODS: The design was a retrospective analysis of a
      family practice clinical database. The setting was a 622-bed suburban teaching
      hospital. The subjects were all acute-care patients (112 short-stay unit and 232
      hospitalized patients) cared for by a family practice residency service during a
      one-year period. The main outcome measures were site of care (inpatient versus
      short-stay unit), hospital length of stay, and in-hospital consultant use.
      RESULTS: When cared for by the same physicians, the elderly are more likely to be
      admitted to the hospital rather than be successfully cared for in a short-stay
      unit (p = 0.001), to stay in the hospital longer (mean days: less than age 20
      years, 5.1; age 80 and older, 8.5; p = 0.004), and to have a greater number of
      consultants (mean number of consultants: less than age 60 years, 0.80; age 60 and
      older, 1.16; p = 0.001). CONCLUSIONS: Our study, in which patient care for
      patients of all ages was provided by one group of family practice residency
      physicians, indicated greater relative health care resource consumption by the
      elderly. We cannot exclude the possibility that age was simply a surrogate for
      unexplored factors, such as insurance status. The generalizability of a study
      from one group in one institution is limited.

PMID- 8296593
TI  - Wegener's granulomatosis & ANCA-associated diseases: the story continues.
      Introduction.

PMID- 8296594
TI  - Friedrich Wegener and the nature of fame.

PMID- 8296595
TI  - ANCA-associated vasculitides. Immunological and clinical aspects. Proceedings of
      the 4th International Workshop on ANCA and the 2nd International Colloquium on
      Wegener's Granulomatosis and Vasculitic Disorders. May 28-30, 1992, Lubeck,
      Germany.

PMID- 8296596
TI  - Lactoferrin co-purifies with myeloperoxidase and is recognised by anti-neutrophil
      cytoplasm antibodies.
AB  - Thirty-five sera with binding greater than 20% in a myeloperoxidase (MPO,
      Calbiochem) ELISA were tested in Western blot analyses. 5/35 blotted MPO, but
      5/35 blotted lactoferrin (LF) contaminating the commercial MPO preparation. All
      the anti-LF positive sera, but none of the anti-MPO positive sera, also exhibited
      anti-nuclear binding on Hep2 cells. Three of the patients with anti-LF antibodies
      had vasculitis affecting areas additional to the pulmonary-renal involvement
      which characterised the patients with anti-MPO antibodies.

PMID- 8296597
TI  - ANCA specificities for HL-60 and neutrophil constituents.

PMID- 8296598
TI  - In vitro interactions of c-ANCA (antibodies to proteinase 3) with human
      endothelial cells.
AB  - Several concepts concerning the pathogenicity of antineutrophil cytoplasmic
      antibodies (ANCA) exist, but till now only sparse data about ANCA-endothelial
      interactions are available. In this study we have investigated the expression of
      proteinase 3 (PR-3) in human umbilical endothelial cells (HEC) using purified
      anti-PR-3 antibodies (C-ANCA) of patients with Wegener's granulomatosis (WG) and
      monoclonal antibodies to PR-3 (human and murine) as probes. Performing cyto
      ELISAs, laser scanning microscopy and Western blot we were able to show that
      treatment of HEC with IL-1-alpha led to an increased PR-3 expression in the
      cytoplasm and to a transient translocation into the EC-membrane. Representing an
      important missing link of ANCA-endothelial interactions, our data give a hint at
      a possible direct pathogenicity of anti-PR-3 antibodies in WG and other
      vasculitides.

PMID- 8296599
TI  - Myeloperoxidase binds to vascular endothelial cells, is recognized by ANCA and
      can enhance complement dependent cytotoxicity.
AB  - Myeloperoxidase (MPO) and proteinase-3 (Pr-3) can bind to vascular endothelial
      cells (EC) and are available for recognition by autoantibodies present in P-ANCA
      or C-ANCA containing sera, respectively. The bound MPO also retains its enzymic
      functions and effectively interacts with hydrogen peroxide to mediate detachment
      of endothelial cells from their substratum. EC bound MPO-anti-MPO complexes can
      contribute to the complement-dependent EC injury demonstrated by some P-ANCA
      sera.

PMID- 8296600
TI  - Vascular permeability changes induced by antibodies to myeloperoxidase.

PMID- 8296601
TI  - Endothelium, myeloperoxidase, anti-myeloperoxidase interaction in vasculitis.

PMID- 8296602
TI  - Further characterization of an animal model of systemic vasculitis.
AB  - The demonstration of vasculitis and anti-myeloperoxidase antibodies in the
      mercuric chloride treated Brown Norway rat provides a useful, though limited,
      animal model of systemic vasculitis. We describe some preliminary experiments on
      the effect of transfer of serum from mercuric chloride treated rats and of two
      forms of immunotherapy: intravenous immunoglobulin and an anti-CD4 antibody.
      Transfer of serum did not lead to tissue injury and neither of the two forms of
      therapy proved beneficial in this model.

PMID- 8296603
TI  - Induction of an humoral and cellular (auto) immune response to human and rat
      myeloperoxidase(MPO) in Brown-Norway(BN), Lewis and Wistar Kyoto(WKY) rat
      strains.
AB  - Anti-MPO and anti-proteinase 3 antibodies are strongly associated with certain
      forms of vasculitis and glomerulonephritis and a pathophysiological role for the
      antibodies has been hypothesized (Kallenberg et al. 1991). To test this
      hypothesis WKY, Lewis and BN rats were immunized with human MPO. BN rats
      developed a strong humoral response, cross reacting with autologous MPO, and
      Lewis rats a strong cellular response to human MPO.

PMID- 8296604
TI  - Disease associations with anti-neutrophil cytoplasmic antibodies.

PMID- 8296605
TI  - Classification of vasculitis.
AB  - The sensitivities and specificities of the classification rules of the seven
      major forms of vasculitis studied varied considerably from 70% to over 99% (Table
      2.) High values as found for giant cell (temporal) arteritis, Takayasu arteritis,
      and Churg-Strauss syndrome, indicate clinically well defined conditions. In
      contrast, the lowest sensitivity and specificity resulted for the classification
      of hypersensitivity vasculitis, in which definitions and manifestations are
      subject to great variation. In a number of instances collection of important
      clinical data was incomplete. This may have had the effect of reducing
      sensitivities and specificities to some extent. Because all the cases studied had
      vasculitis, these criteria are not appropriate to use for diagnosis of individual
      patients. Development of diagnostic criteria also requires comparison of patients
      who do not have vasculitis. Development of criteria by two different methods
      provides some flexibility. Both formats should prove easy to use. Although biopsy
      is not needed in all patients for classification purposes, histology should be
      performed as frequently as possible to document the vasculitic nature of the
      disorder. These criteria sets should be used in the description of patients with
      vasculitis to enhance uniformity of reporting. As other characteristics of these
      disorders are identified, more accurate classification rules may be revised.

PMID- 8296606
TI  - Neutrophilic leukocyte granules: from structure to function.

PMID- 8296607
TI  - Vasculitis from the rheumatologist's viewpoint.

PMID- 8296608
TI  - A nephrological view of the classification of vasculitis.
AB  - From the nephrologic perspective, a nomenclature system has been proposed that is
      clinically useful for diagnosis, classification and therapy. This nomenclature
      allows the nephrologist to consider the best approach to ANCA positive patients
      with necrotizing and crescentic glomerulonephritis. It allows for better
      understanding of the extra-renal manifestations of disease especially those with
      pulmonary-renal syndrome. The classification system allows for the rapid
      introduction of immunosuppressive therapy in individuals without repetitive
      search for specific pathological features on biopsy. This classification system
      allows for the possibility that all of these conditions are pathogenically
      related. As such, it separates this group of diseases from those which are
      attributable to immune complex disease or direct antibody binding. For this
      nomenclature system to stand the test of time it must be simple, logical and
      clinically usefully. While not yet perfected, the working nomenclature for ANCA
      associated diseases is a step forward.

PMID- 8296609
TI  - The nosology of Wegener's granulomatosis utilizing the elk format augmented by c
      ANCA.

PMID- 8296610
TI  - Vasculitis--the neurologist's view.

PMID- 8296611
TI  - Monoclonal antibody therapy for vasculitis.

PMID- 8296612
TI  - Heterogeneity of ANCA sera showing atypical, peripheral and classical cytoplasmic
      immunofluorescence patterns.
AB  - Atypical (A) ANCA immunofluorescence (IF) patterns have been described in several
      disease groups. We have previously reported a distinct cytoplasmic A-ANCA in 7
      10% of patients with SLE and/or RA. Here, we show that these rheumatic disease
      associated A-ANCAs are best identified using U937 cells as substrate and that
      they do not target either a serine proteinase or a peroxidase. Furthermore, these
      sera immunoprecipitate a 40 kDa or a 42 kDa band using in vivo 35S-amino acid
      labelled HL60 or U937 cell extracts, respectively. Although these bands are the
      only one seen with pure A-ANCA sera, they can also be found in addition to the
      expected bands of PR3 or MPO in up to 30% of bona fide C- or P-ANCA sera. These
      data confirm and extend our previous observations. They also suggest that target
      heterogeneity of ANCA antibodies is frequent. Care should thus be taken in
      interpreting in a cause and effect relationship, an IF pattern or a biological
      effect produced by a serum with ill documented monospecificity. The exact nature
      and significance of this (these) new antigen(s) have yet to be clarified.

PMID- 8296613
TI  - ANCA in systemic vasculitides, collagen vascular diseases, rheumatic disorders
      and inflammatory bowel diseases.
AB  - It was the aim of this study to reevaluate the diagnostic significance and
      clinical implication of ANCA after testing sera from 13,606 patients for the
      presence of ANCA. Our data confirm the high specificity (97%) and sensitivity
      (80%) of cANCA for Wegener's granulomatosis. pANCA were found in renal
      vasculitides (60%), collagen vascular diseases (SLE 20%, Sjogren's syndrome 26%,
      polymyositis 16%) and rheumatic disorders (Felty's syndrome 50%, rheumatoid
      arthritis 20%). A third fluorescence pattern in sera of patients with
      inflammatory bowel disease (ulcerative colitis 28/72, Crohn's disease 6/84), here
      called xANCA, was seen. Target antigens of granule proteins from PMN and
      monocytes (proteinase 3, myeloperoxidase, elastase, cathepsin G, lactoferrin,
      lysozyme) were identified.

PMID- 8296614
TI  - Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA): clinical significance
      and relation to antibodies against myeloid lysosomal enzymes.
AB  - In a prospective study of 27 months duration p-ANCA were found in 120 patients.
      35% of these patients had vasculitis and/or glomerulonephritis. 28% of the p-ANCA
      positive sera reacted with myeloid lysosomal enzymes.

PMID- 8296615
TI  - Methods of detection of anti-cathepsin G autoantibodies in human.
AB  - Anti-cathepsin G antibodies have been detected by using three different methods.
      i) Binding to azurophilic granules constituents after separation of purified
      alpha-granules on Matrex gel Orange A chromatography according to Kao. ii)
      Binding to azurophilic granules freezed and thawed after coating on ELISA plates.
      iii) Binding to purified cathepsin G in ELISA assay. Anti-cathepsin G antibodies
      were observed patient's sera with ulcerative colitis, primary sclerosing
      cholangitis, primary biliary cirrhosis and autoimmune hepatitis but not in
      controls or patients with chronic viral hepatitis or vasculitis.

PMID- 8296616
TI  - Anti-myeloperoxidase antibodies and associated diseases.
AB  - Thirty five (41%) sera presented anti MPO specificity, 26 of them (74%) having a
      p-ANCA pattern. They were present in patients with vasculitis and isolated or
      predominant renal involvement, but also in 24% of Wegener patients.

PMID- 8296617
TI  - Autoantibodies directed against lysozyme: a new target antigen for anti
      neutrophil cytoplasmic antibodies (ANCA).
AB  - ANCA-positive sera from 1138 patients and ANCA-negative sera from 90 patients
      were screened for autoantibodies directed against lysozyme (LZ) by ELISA. Sera
      from 120 patients did react with LZ. 99 sera bound to LZ only, whereas 56 sera
      bound to further granule proteins, especially cathepsin G and lactoferrin. In the
      routine ANCA screening, most of the anti-LZ-positive sera showed a pANCA
      fluorescence. In total, 8% of 674 pANCA-positive sera did react with LZ.
      Clinically, anti-LZ antibodies were associated inflammatory rheumatologic, -renal
      and -bowel diseases.

PMID- 8296618
TI  - Anti-neutrophil cytoplasmic autoantibodies (ANCA): antigenic specificities and
      clinical associations.
AB  - We have conducted a prospective study of 372 patients with well-defined forms of
      systemic vasculitis and connective tissue diseases to determine the prevalence,
      the antigenic specificities and the clinical associations of ANCA in such cases.
      These antibodies were detected by indirect immunofluorescence on ethanol-fixed
      neutrophils and also by enzyme-linked immunosorbent assay using myeloperoxidase
      (MPO) as a substrate. In our study, ANCA with a cytoplasmic immunostaining
      pattern were mainly found in patients with biopsy-proven Wegener's granulomatosis
      with or without renal involvement and pulmonary hemorrhage. Furthermore, MPO-ANCA
      strongly correlated with necrotizing glomerular and alveolar capillaritis, mostly
      in patients having a well-established diagnosis of polyarteritis nodosa.

PMID- 8296619
TI  - Significance of autoantibodies to purified proteinase 3 in systemic vasculitis.
AB  - Proteinase 3 was purified from human neutrophils and used in ELISA to examine
      sera from 150 patients with systemic vasculitis. It was found to be the major
      target of autoantibodies in Wegener's granulomatosis, and anti-proteinase 3
      antibodies were also found in some patients with microscopic polyarteritis. Anti
      proteinase 3 antibodies were associated with a chronic relapsing course.

PMID- 8296620
TI  - Low predictive value of c-ANCA and anti-alpha-granule antibody for vasculitis in
      Hong Kong.
AB  - One thousand sera, not previously tested for ANCA, were assayed for C-ANCA and
      anti-alpha-granule antibody. There was low concordance (23%) between the two
      assays in terms of positivity. Each assay gave a positive predictive value for
      systemic vasculitis excluding SLE and other connective-tissue diseases) of not
      more than 20%.

PMID- 8296621
TI  - Detection and clinical associations of autoantibodies to myeloid granular
      proteins.

PMID- 8296622
TI  - Relationship between disease activity and ANCA level by ELISA in the long-term
      management of vasculitis.
AB  - Solid-phase immunoassays were used to examine the relationship between ANCA
      concentration and disease activity during follow-up of 63 patients with systemic
      vasculitis. ANCA levels fell with induction therapy. Relapses during long-term
      follow-up were generally associated with high or rising ANCA concentrations,
      although the temporal relationship between clinical relapse and changes in ANCA
      was variable.

PMID- 8296623
TI  - ANCA in ocular inflammatory disorders.
AB  - 400 patients presenting with active inflammation of the conjunctiva, sclera,
      orbita, uvea or retina were cANCA negative during active disease, however, pANCA
      were found in 15%. Another group of 100 patients suffering from Wegener's
      granulomatosis (WG) showed in 72 cases one or multiple ocular inflammatory
      symptoms. They were frequently cANCA-positive. Contrary to some other reports
      dealing with ocular inflammation, we find a high specificity of cANCA for
      Wegener's granulomatosis and, therefore, recommend cANCA-testing in all ocular
      inflammatory disorders, which may be difficult to differentiate from a
      manifestation of WG.

PMID- 8296624
TI  - Head and neck involvement in Wegener's granulomatosis (WG).
AB  - Review of 411 patients with Wegener's granulomatosis showed that involvement of
      the head and neck region is extremely common. Early diagnosis and prompt
      treatment resulted in better survival rates--75% alive at 5.8 years.

PMID- 8296625
TI  - Orbital involvement in Wegener's granulomatosis.
AB  - Orbital granulomas may complicate the course of Wegener's granulomatosis (WG).
      Granulomas that grow and compress the optic nerve may lead to blindness. Careful
      magnetic resonance imaging (MRI) is recommended for early detection and follow-up
      of intraorbital granulomas. Sufficient systemic immunosuppressive treatment
      should be given as usual for Wegener's granulomatosis. In order to preserve
      vision orbital decompression may be necessary in rapidly progressive pseudotumor
      of the orbit.

PMID- 8296626
TI  - MRI of the head in Wegener's granulomatosis.
AB  - MRI of the head was performed in 25 patients suffering from Wegener's
      granulomatosis. 23 patients showed mucosal inflammation in the nasal cavity and
      in the paranasal sinuses, 10 patients had granulomas in the paranasal sinuses and
      in the orbits, 7 patients had cerebral lesions, 3 patients had submucosal
      hemorrhages in the paranasal sinuses and 3 patients showed bone erosions or
      destructions in the facial skeleton, which was visible only by CT.

PMID- 8296627
TI  - The clinical, serologic, and immunopathologic heterogeneity of cutaneous
      leukocytoclastic angiitis.
AB  - Histologically identical cutaneous leukocytoclastic angiitis occurs in patients
      with different serologic markers for vasculitis. When categorized on the basis of
      serologic analysis for antineutrophil cytoplasmic autoantibodies and IgA
      fibronectin aggregates, categories of leukocytoclastic angiitis have many
      overlapping features; however, there are distinctive clinical and
      immunopathologic trends among the categories. When both serologic tests are
      negative, there is a low probability that systemic vasculitis is present. The
      presence of either serologic marker indicates a strong probability for the
      presence of extracutaneous vasculitis and/or glomerulonephritis.

PMID- 8296628
TI  - No ANCA in thromboangiitis obliterans (Burger's disease).
AB  - Sera of 30 patients with clinically well established Thromboangiitis obliterans
      were tested for the presence of ANCA by means of immunofluorescence and ELISA.
      ANCA did occur neither in active nor in inactive disease.

PMID- 8296629
TI  - Alpha-1-proteinase inhibitor and pulmonary haemorrhage in systemic vasculitis.
AB  - Alpha-1-proteinase inhibitor phenotypes and levels were examined in 40
      antineutrophil cytoplasmic antibody positive cases of systemic vasculitis. An
      excess of PiZ and PiS alleles were associated with the development of pulmonary
      haemorrhage and alpha-1-proteinase inhibitor levels were lower in the subgroup
      with pulmonary haemorrhage. However, this allelic imbalance and reduced alpha-1
      proteinase inhibitor level was not confined to antiproteinase 3 positive patients
      and did not appear to be associated with other organ involvement or disease
      severity.

PMID- 8296630
TI  - Alpha-1-antitrypsin, CRP and interleukin-6 in ANCA-positive vasculitis.
AB  - Alfa-1-antitrypsin (a-1-AT), C-reactive protein (CRP) and interleukin-6 (IL-6)
      serum levels were measured during different phases of anti-neutrophil cytoplasmic
      antibody (ANCA)-positive vasculitis. Correlation between ANCA and these variables
      was observed. Both a-1-AT and CRP fluctuations indicated changes in activity that
      could not always be detected by ANCA. On the other hand, these acute phase
      proteins were also less specific. IL-6 was not as sensitive as CRP and a-1-AT, a
      clearly increased mean value was observed only in patients with high ANCA titers.

PMID- 8296631
TI  - Pro- and anti-inflammatory cytokines in primary systemic vasculitis.
AB  - The expression of cytokines that are potentially involved in the pathogenesis of
      vasculitis was studied in patients with primary systemic vasculitis (PSV). In
      extension of earlier reports, we detected an overexpression of transforming
      growth factor beta (TGF beta), interleukin 6 (IL6), and interleukin 8 (IL8),
      indicating that the whole cytokine cascade is activated to a significant extent
      in PSV.

PMID- 8296632
TI  - Problems of classification in necrotizing vasculitis.

PMID- 8296633
TI  - Anti-neutrophil cytoplasm antibodies in HIV infection.
AB  - Sera from 105 HIV-infected patients were tested for anti-neutrophil cytoplasm
      antibodies (ANCA) by indirect immunofluorescence (IIF), by specific ELISAs using
      target proteins of ANCA and by a neutrophil cytoplasm extract ELISA. Forty-four
      sera were positive. These included 18 positive by IIF, 7 with anti-neutrophil
      proteinase 3 antibodies, 26 with anti-myeloperoxidase antibodies and 2 with anti
      elastase antibodies. Four sera were positive in the neutrophil cytoplasm extract
      ELISA but not in the specific ELISAs. None of these patients had clinical
      evidence of a cutaneous or systemic vasculitis. In addition there was no
      correlation between the presence of ANCA and the stage of disease, intercurrent
      bacterial or viral infection, anti-nuclear antibodies (ANA) and positive
      hepatitis B or syphilis serology.

PMID- 8296634
TI  - Anti-neutrophil cytoplasmic antibodies (ANCA) and infection.
AB  - As ANCA are occasionally noted in patients with infectious disorders
      independently of any vasculitis process, we examined serum from patients with
      acute infection (n = 22) and septic shock (n = 57). Only two patients with acute
      infection were ANCA positive as determined by indirect immunofluorescence and
      western blot analysis. The clinical recovery of both patients was associated with
      negative immunofluorescence and western blot tests.

PMID- 8296635
TI  - Anti-lactoferrin antibodies in patients with rheumatoid arthritis with
      vasculitis.
AB  - Anti-lactoferrin antibodies (anti-LF Ab) are more frequently found in patients
      with rheumatoid arthritis (RA) complicated by vasculitis when compared to
      patients with uncomplicated RA. Therefore the detection of anti-LF Ab in serum of
      patients with RA may be useful in the diagnosis of vasculitis in RA patients.

PMID- 8296636
TI  - Anti-neutrophil cytoplasmic antibodies in giant cell arteritis and polymyalgia
      rheumatica.
AB  - Antineutrophil cytoplasmic antibodies (ANCA) were demonstrated in all sera from
      11 patients with active giant cell arteritis (GCA) using indirect
      immunofluorescence on 9% paraformaldehyde(PF)-fixed neutrophils according to
      Pryzwanski (median titer 1:256, range 1:64 to 1:512). After treatment during
      inactive disease titers decreased in all sera. Eight out of 9 sera from patients
      with active polymyalgia rheumatica (PMR) produced a cytoplasmic staining on
      Pryzwanski-fixed neutrophils in low titers (median titer 1:16, range 0 to 1:32),
      as did 8 out of 25 sera from healthy blood donors. None of the sera were positive
      for antibodies to defined antigens, i.e. proteinase-3, human leucocyte elastase,
      myeloperoxidase and lactoferrin as detected by ELISA. GCA seems to be associated
      with ANCA of as yet unknown specificity.

PMID- 8296637
TI  - Antibodies to neutrophil cytoplasmic antigens in rheumatoid arthritis.
AB  - In this study we examined the sera from 42 randomly selected patients with RA.
      ANCA was demonstrated by indirect immunofluorescence on human granulocytes in 10
      patients with active disease and in none of the patients with inactive disease.
      ELISA's for the detection of specific antigens showed the presence of anti
      myeloperoxidase in 3 patients, and anti-lactoferrin in 1 patient. The specificity
      of the remaining antibodies was unidentified. All 3 patients with antibodies to
      myeloperoxidase had vasculitis.

PMID- 8296638
TI  - Incidence and specificity of p-ANCA in rheumatic diseases.

PMID- 8296639
TI  - Anti-granulocyte perinuclear antibodies but not anti-neutrophil cytoplasmic
      antibodies (ANCA) in rheumatoid arthritis.
AB  - We studied 45 patients with rheumatoid arthritis for the presence of ANCA. These
      antibodies were determined by indirect immunofluorescence (IIF) and by enzyme
      linked immunosorbent assays (ELISAs) using as a substrate purified
      myeloperoxidase and purified extract of azurophilic granules. By IIF, we found a
      characteristic perinuclear immunostaining pattern in 21 cases (47%). However, no
      patient had a positive result by the two ELISAs performed. Patients with a
      positive IIF result had significantly higher levels of anti-nuclear and anti-ds
      DNA antibodies than those with a negative IIF result. Therefore, these antibodies
      must correspond to the previously reported as granulocyte specific antinuclear
      antibodies (GS-ANA).

PMID- 8296640
TI  - Anti-neutrophil cytoplasmic antibodies in patients with systemic lupus
      erythematosus.
AB  - Autoantibodies against neutrophil cytoplasmic antigens (ANCA) are found in
      patients with different kinds of systemic vasculitis and glomerulonephritis, both
      characteristic manifestations of systemic lupus erythematosus (SLE). The present
      study was designed to clarify the nature of ANCA seen in SLE patients and their
      correlation with the clinical findings.

PMID- 8296641
TI  - ANCA with specificity for lactoferrin in systemic lupus erythematosus (SLE).
AB  - Antibodies to lactoferrin were detected in about 20% of patients with SLE,
      irrespective of the presence of renal involvement and in 10% of patients with
      rheumatoid arthritis and in 19% of patients with scleroderma. We conclude that
      anti-lactoferrin antibodies may be found in different types of connective tissue
      disease. Their clinical significance in these diseases however remains to be
      elucidated.

PMID- 8296642
TI  - Serum markers of T-cell activation in relapses of Wegener's granulomatosis.
AB  - Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were
      measured by sandwich ELISA as markers for T-cell activation in serial serum
      samples drawn monthly from 16 patients showing 18 histologically proven relapses
      of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1162 U/ml
      (median, 95% CI 843 to 1814 U/ml) at three months before the relapse to 1684 U/ml
      (95% CI 1254 to 2202 U/ml) at the time of relapse for the whole group (P = 0.10).
      The 8 major relapses showed a profound rise in sIL-2R levels (P < 0.01). The
      level of sIL-2R at the moment of relapse correlated with the level of C-reactive
      protein (r = 0.547, P < 0.05) and with the disease activity score (r = 0.814, P <
      0.001). There were no significant changes in levels of sCD4 or sCD8.

PMID- 8296643
TI  - Presence of anticardiolipin antibodies discriminates between Wegener's
      granulomatosis and microscopic polyarteritis.
AB  - ANCA-tests are not always useful in evaluation of disease activity of patients
      with Wegener's granulomatosis (WG) and microscopic polyarteritis(MP). If ANCA
      tests are failing in patients with Wegener's granulomatosis or microscopic
      polyarteritis, markers of activated coagulation are helpful in evaluation of
      disease activity. The measurement of anticardiolipin antibodies(ACA) may allow to
      discriminate between MP and WG, since ACA are only significantly elevated in
      patients with MP. Anticardiolipin antibodies (ACA) are acquired autoantibodies
      that are found in patients with a wide spectrum of clinical conditions, mainly
      systemic lupus erythematosus and related disorders. They are associated with
      increased thrombotic tendency. We investigated in patients with ANCA-positive
      vasculitis whether membrane phospholipids exposed in injured endothelial cells
      might stimulate the formation of ACA, thus contributing to the vascular
      thrombotic occlusion besides the activation of coagulation.

PMID- 8296644
TI  - Wegener's granulomatosis with severe peripheral and central neuropathy--case
      report.

PMID- 8296645
TI  - Limited prognostic value of changes in antineutrophil cytoplasmic antibody titers
      in patients with Wegener's granulomatosis.
AB  - One hundred and six patients with Wegener's granulomatosis (WG) were studied for
      the presence of antineutrophil cytoplasmic antibodies (ANCA). In 53 patients
      serial ANCA determinations were obtained. C-ANCA positivity was a sensitive (88%)
      marker of active WG. However, changes in serial titers were temporally concordant
      with a change in disease status in only 55% of patients. Furthermore, a rise in c
      ANCA titer preceded clinical exacerbation of disease in only 24% of patients who
      had been in remission or had low grade, smoldering disease. A rise in c-ANCA
      titer alone should not be considered a priori evidence of impending relapse, and
      does not justify modification of immunosuppressive therapy.

PMID- 8296646
TI  - Wegener's granulomatosis and Henoch-Schonlein purpura in a family with hereditary
      C4 deficiency.
AB  - Described here is a family in which the father with partial C4 deficiency had
      Wegener's granulomatosis and a son with complete C4 deficiency presented with
      Henoch-Schonlein Purpura. The possible role of C4 deficiency in the pathogenesis
      of both vasculitic disorders is discussed.

PMID- 8296647
TI  - Little evidence for anti-endothelial-cell antibodies in microscopic polyarteritis
      and Wegener's granulomatosis.
AB  - Sera from patients with a vasculitis and controls were investigated for the
      presence of anti-endothelial cell antibodies(AECA), anti- neutrophil cytoplasmic
      antibodies(ANCA) and anti-myeloperoxidase (MPO) antibodies. Only 19% of patients
      with Wegener's granulomatosis and 2% of patients with microscopic polyarteritis
      had AECA. Our data suggests that AECA are a minor antibody system in vasculitis.

PMID- 8296648
TI  - Prevalence of ANCAs in patients on maintenance haemodialysis.
AB  - ANCA analysis as evaluated by concomitant determination of ANCA-IF, PR3-AB and
      MPO-AB in a larger cohort of dialysis patients disclosed that the prevalence of
      Wegener's granulomatosis and microscopic polyarteritis in Germany is 4 fold
      higher than hitherto believed. Low ANCA-IF titers without measurable PR3-AB or
      MPO-AB are not pathological- they resemble an increased autoimmune tendency of
      the dialysis patients. According to the european dialysis and transplantation
      association (EDTA)-registry the incidence of Wegener's granulomatosis (WG) and
      microscopic polyarteritis (MP) on haemodialysis (HD) in Germany is 0.5% and the
      prevalence is in the same range (1). In contrast to Germany the incidence in
      France and Great Britain is above 2%. This is mainly based on histologically
      proven diseases, which can identify only 1/3 of all affected cases, corresponding
      to our own experience. With the advent of ANCA serology, WG and MP can be
      diagnosed more easily. C-ANCA with proteinase 3-antibodies (PR3-AB) is typical of
      WG, and p-ANCA with myeloperoxidase-antibodies (MPO-AB) is typical of MP in our
      country. Since a considerable number of patients are on chronic HD without
      knowledge of their underlying renal disease we studied the prevalence of ANCAs in
      a larger cohort of HD patients.

PMID- 8296649
TI  - Rhabdomyolysis in vasculitis.

PMID- 8296650
TI  - Rapidly progressive glomerulonephritis (RPGN): is there still an "idiopathic"
      subgroup?
AB  - In order to clarify if "idiopathic" RPGN still exists as a distinct entity we
      reviewed 41 patients with histological picture of diffuse crescentic GN (60% of
      crescents) and no clinical evidence of systemic disease. According to the
      presence or absence of intraglomerular necrotizing lesions we subdivided the
      patients into two different morphological groups: Group I (25 pts) with
      necrotizing GN and massive periglomerular infiltrates; Group II (16 pts) with
      intra-extracapillary proliferation and no interstitial infiltrates. Our data
      suggest that "idiopathic" RPGN does not exist as a distinct entity, but is an
      expression either of renal limited vasculitis or crescentic GN complicating
      primary proliferative GN.

PMID- 8296651
TI  - Association between silica exposure and necrotizing crescentic glomerulonephritis
      with p-ANCA and anti-MPO antibodies: a hospital-based case-control study.
AB  - A hospital-based case-control study was carried out to investigate the
      association between ANCA positive rapidly progressive glomerulonephritis (RPGN)
      and occupational exposure to silica dust. All ANCA positive male patients
      admitted to the Department of Nephrology of the University of Brescia between
      1987 and 1992 were enrolled in the study as cases. The controls were pts of the
      same age, admitted at the Department immediately before or after the cases,
      affected by other renal diseases. Seven of the 16 cases and one of the 32
      controls, had a positive history for jobs exposing to silica dust (relative risk
      14; 95% C.I.: 1.7-113.8, p < 0.001). ANCA pattern was p-ANCA with anti-MPO
      antibodies in 6/7 of exposed pts. The review of renal histology showed a
      distinctive glomerular lesion consisting in peripheral nodular areas of
      glomerular sclerosis, in addition to the crescentic necrotizing
      glomerulonephritis, in 3/6 silica exposed pts, but in none of the unexposed pts.

PMID- 8296652
TI  - ANCA and anti-GBM antibodies in RPGN.
AB  - ANCA and anti-GBM antibodies can occur together in RPGN. These patients are rare
      and have two distinct populations of antibodies and the ANCA specificity tends to
      be for myeloperoxidase more often than expected.

PMID- 8296653
TI  - p-ANCA with myeloperoxidase antibodies and c-ANCA with proteinase 3 antibodies
      define a different vasculitis entity in patients with renal involvement.
AB  - In a 3 year period 359/3685 patients with suspected vasculitis had a positive
      ANCA-IF. C-ANCA were found in 146/359 and p-ANCA in 213/359 patients. P-ANCA and
      MPO-antibodies were more frequently associated with female gender and
      preglomerular vasculitis, whereas c-ANCA (WG) were more frequent in males without
      renal vasculitis. Detection of anti-neutrophil cytoplasmic antibodies (ANCA) has
      facilitated the diagnosis of Wegener's granulomatosis (WG) and microscopic
      polyarteritis (MP), important representatives of small vessel vasculitides (SVV).
      C-ANCA with proteinase 3 antibodies (PR 3-AB) are typical of WG and p-ANCA with
      myeloperoxidase antibodies (MPO-AB) are typical of MP in our country. We reported
      recently about an association between crescentic glomerulonephritis, renal
      vasculitis, p-ANCA, myeloperoxidase-AB and female gender in a small cohort of
      patients with rapidly progressive glomerulonephritis (RPGN). In the following we
      analyzed whether in a larger cohort of patients with SVV this preliminary
      statements could be confirmed.

PMID- 8296654
TI  - Antineutrophil-cytoplasmic-autoantibodies in poststreptococcal nephritis.
AB  - Sera from 210 patients with APSGN, were tested for the presence of ANCA (IgG
      isotype). Indirect immunofluorescence (IF) on ethanol fixed human PMNs was used,
      and for those positive sera, ELISA kits for PR3 (Proteinase 3) and MPO
      (Myeloperoxidase) was performed. ANCA were detected in 9% (18 out of 210 cases)
      in a predominantly diffuse cytoplasmic staining pattern in 14 cases (77%), and in
      a perinuclear pattern in the remaining 4 cases (22%). Anti-MPO was found in 4
      cases (C-ANCA 3; P-ANCA 1) and anti-PR3 was always negative. The presence of ANCA
      was significantly associated with a more severe glomerular disease as assessed by
      the serum creatinine value and the crescents formation. Longitudinal studies
      performed in 11 cases have shown that raised levels of these autoantibodies may
      persist for at least six months, without relationship with disease activity.
      Further studies are required to dilucidate the specificity of these
      autoantibodies, and if its presence is either an epiphenomenon of the
      heterogeneous humoral immune response in streptococcal infection, or they play
      some pathogenic role in APSGN.

PMID- 8296655
TI  - Membrane surface proteinase 3 expression and intracytoplasmic immunoglobulin on
      neutrophils from patients with ANCA-associated vasculitides.
AB  - We studied the presence of proteinase 3 (PR3), myeloperoxidase (MPO) and elastase
      (HLE) on the plasma membrane of neutrophils in patients with biopsy-proven
      Wegener's disease (WG), pANCA-positive vasculitis, control patients (SLE,
      rheumatoid arthritis, ankylosing spondylitis), sepsis patients and healthy
      donors. We found an overexpression of PR3 on the cell surface of neutrophils in
      WG, ANCA-associated vasculitis and during infection (sepsis). Thus PR3 becomes
      accessible to ANCA. Furthermore we detected intracytoplasmic IgG antibodies in
      PMN from patients with WG by immunoelectron microscopy and direct
      immunofluorescence. Our findings support the pathophysiological role of ANCA.

PMID- 8296656
TI  - Identification of apparent dual ANCA specificities in a subset of patients with
      systemic vasculitis and crescentic glomerulonephritis.
AB  - 23% of a random selection of ANCA (+) patients had dual, non-cross reactive
      autoantibody specificities. We found no clinical difference in such patients as
      compared to those having a single antibody. A second group of ANCA (+) patients
      had neither anti-MPO nor anti-PR3 autoantibody specificity. These findings
      suggest that multiple, coincident ANCA specificities occur more commonly than
      previously reported, and that additional, unidentified ANCA specificities are
      present in some patients.

PMID- 8296657
TI  - C-ANCA and p-ANCA positive vasculitis with crescentic glomerulonephritis: the
      same clinical feature but different immunological pathways?
AB  - Patients with cytoplasmatic (c)-ANCA positive vasculitis and crescentic
      glomerulonephritis (n = 25) had similar clinical presentation, age, sex
      distribution, organ involvement, therapy requirements, and outcome as patients
      with perinuclear (p)-ANCA positive vasculitis and crescentic glomerulonephritis
      (n = 7). Therefore, we conclude that these two entities are very closely related
      or even the same disease.

PMID- 8296658
TI  - Clinical manifestations in patients on chronic dialysis with high titres of ANCA.
AB  - Eight untreated patients with an apparent renal-limited disease continued to
      maintain high titres of ANCA long after the onset of the disease and the start of
      dialysis. In spite of the high ANCA titres, three of them remained for a long
      time free of symptoms related to the disease. Three pts developed, at various
      times from the beginning of the disease, fatal pulmonary hemorrhages.

PMID- 8296659
TI  - Pooled intravenous immunoglobulin in the management of systemic vasculitis.
AB  - Investigation into the therapeutic use of intravenous immunoglobulin (IVIg) in
      systemic vasculitis was prompted by the detection of anti-idiotype antibodies
      reactive with ANCA in IVIg and the proven ability of IVIg to reduce the incidence
      of coronary artery aneurysms in Kawasaki disease. The efficacy and safety of IVIg
      (Sandoglobulin) was assessed in an open study of 26 patients with active systemic
      vasculitis. Eight weeks after IVIg 13 patients were in full and 13 in partial
      remission, clinical benefit was maintained in 18 twelve months later and was
      reflected by changes in C-reactive protein and ANCA.

PMID- 8296660
TI  - Cyclosporin A therapy for Wegener's granulomatosis.
AB  - Five patients with active Wegener's granulomatosis were treated with the
      immunosuppressive agent Cyclosporin A, along with low dose prednisone. All five
      patients had previously taken cyclophosphamide, but further treatment with this
      agent was not desired, either due to patient choice, drug toxicity or malignancy.
      In initial doses of up to 5mg/kg/day, CyA showed efficacy but when lowered to 1
      2mg/kg/day, mild disease flares occurred. CyA may provide an alternative to
      traditional therapy in selected patients with WG.

PMID- 8296661
TI  - Effectiveness of cyclophosphamide pulse treatment in Wegener's granulomatosis.
AB  - 43 patients with Wegener's granulomatosis were studied to evaluate the
      effectiveness of cyclophosphamide (cyc) pulse treatment. 42% of the patients
      showed benefits from treatment for at least 6 months after the cessation of cyc
      pulses. Analysis of clinical and laboratory parameters indicate that this
      treatment is less effective in patients in whom more than 4 organ systems are
      involved. Responders to the treatment showed disease manifestations predominantly
      in the ENT and lower respiratory tract and had lower cANCA titers (< 1:64) prior
      to treatment.

PMID- 8296662
TI  - Treatment of Wegener's granulomatosis with intravenous immunoglobulin.
AB  - We report about the treatment of eight patients with Wegener's granulomatosis and
      one patient with systemic pANCA-associated vasculitis with a single course of
      high-dose intravenous immunoglobulin (IVIG). In 5 of 9 patients (55%) this
      resulted in significant clinical improvement, in two patients a decrease of the
      ANCA-titre was seen.

PMID- 8296663
TI  - Treatment of Wegener's granulomatosis.
AB  - Treatment and outcome of 111 patients who fell ill with Wegener's granulomatosis
      (WG) between 1966 and 1990 were analysed retrospectively. Two regimens of
      treatment were distinguished: "conventional" treatment, i.e. daily application of
      cyclophosphamide/corticosteroids (FAUCI scheme) or azathioprine/corticosteroids
      or corticosteroids alone, and "stage-adapted" treatment, characterized by change
      of different treatments (e.g. cyclophosphamide pulse therapy, cotrimoxazole)
      according to the extent and activity of disease. In patients who received stage
      adapted treatment, exacerbations occurred significantly more frequent than in
      conventionally treated patients, while lethal outcome was much more frequent in
      conventionally treated patients.

PMID- 8296664
TI  - Late recurrence of systemic vasculitis after kidney transplantation involving the
      kidney allograft.
AB  - A patient is described in whom a recurrence of vasculitis was observed in the
      kidney allograft six years after transplantation and one year after withdrawal of
      corticosteroid therapy. This case shows that systemic vasculitis may recur at any
      time after transplantation which implies a continuous and careful monitoring of
      these patients.

PMID- 8296665
TI  - p-ANCA of undefined specificity in ulcerative colitis: correlation to disease
      activity and therapy.
AB  - Sera of 108 patients with chronic inflammatory bowel disease (IBD) and 13 sera
      from patients with other gastrointestinal diseases were screened for antibodies
      against neutrophil cytoplasmic antigens (ANCA) by an indirect immunofluorescence
      test. 37 out of 64 sera (58%) from patients with ulcerative colitis (UC) produced
      a fine granular and perinuclear ANCA staining pattern ("snowdrift-like" p-ANCA)
      clearly different from the cytoplasmic ANCA fluorescence (c-ANCA) seen in active
      Wegener's granulomatosis (WG) and the typical p-ANCA pattern produced by anti
      myeloperoxidase (MPO) autoantibodies. Only 1 of 44 sera from patients with
      Crohn's disease (CD) and none of the control sera showed positive "snowdrift
      like" p- ANCA reactions. 31 out of the 37 p-ANCA positive sera (84%) were
      obtained from patients with high disease activity with and without longterm high
      dose steroids. p-ANCA titers became negative after longterm steroid therapy and
      following complete colectomy.

PMID- 8296666
TI  - A new approach to the molecular characterization of the c-ANCA antigen in
      Wegener's granulomatosis.
AB  - Classic anti-neutrophil cytoplasmic antibodies (c-ANCA) specific for constituents
      of neutrophil primary granules and monocyte lysosomes have been implicated in the
      pathogenesis of Wegener's Granulomatosis (WG). The revised amino-terminal
      sequence of Proteinase 3 (PR-3) as ANCA antigen, suggested that PR-3 is identical
      to myeloblastin (MBN). As it has been proposed that autoantibodies recognize a
      conformational epitope on c-ANCA, prokaryotic expressed protein might not be
      recognized by the patients sera. Therefore we set up an in vitro translation in
      an eukaryotic cell-free system using an internal ATG (amino acid 15 of the mature
      protein).

PMID- 8296667
TI  - Anti-neutrophil cytoplasmic auto-antibodies (ANCA) in patients with ulcerative
      colitis (UC): influence of disease activity and familial study.

PMID- 8296668
TI  - Antineutrophil antibodies in inflammatory bowel disease recognize different
      antigens.
AB  - Anti-neutrophil cytoplasmic antibodies (ANCA) were observed in 31 out of 68 sera
      (45%) from Ulcerative Colitis (UC) patients and in 13 out of 38 Crohn's Disease
      (CD) sera (34%). The presence of ANCA was not related to disease activity, nor to
      the localization of the disease manifestations. By Western Blotting ANCA showed
      reactivity with either lactoferrin, polypeptides occurring as a doublet of 66/67
      kD MW, or polypeptides occurring as a doublet of 63/54 kD MW.

PMID- 8296669
TI  - Antineutrophil cytoplasmic auto-antibodies in sera from patients with ulcerative
      colitis after proctocolectomy with ileo-anal anastomosis.
AB  - Presence of antineutrophil cytoplasmic auto-antibodies (ANCA) in ulcerative
      colitis could be an epiphenomenon related to colonic inflammation and/or may
      reflect a primitive disturbance of immune regulation. In this regard, study of
      ANCA status after the whole colorectal mucosa has been removed could favor one of
      these two hypothesis. We compared the prevalence of ANCA in a first group of 70
      patients with non operated UC and in a second group of 32 patients with UC having
      had a proctocolectomy with ileoanal anastomosis. Perinuclear ANCA (p-ANCA) were
      found in 34/70 (49%) of the first group as compared to 11/32 (34%) in the second
      group (NS). Our results further support that the presence of ANCA in UC reflects
      an immune disturbance not linked to the presence of the target organ.

PMID- 8296670
TI  - p-ANCA as a diagnostic marker in ulcerative colitis.
AB  - P-ANCA that do not react with myeloperoxidase (MPO) have been claimed to serve as
      a useful diagnostic marker in the differential diagnosis of inflammatory bowel
      disease (IBD). Therefore, in this study we determined the frequency of MPO
      negative-p-ANCA in patients with inflammatory bowel disease and correlated the
      presence with intestinal and extra-intestinal disease manifestation. In 44 out of
      65 (68%) sera from patients with ulcerative colitis (UC) but in only 14 of 66
      (21%) with Crohn's disease (CD) MPO-negative-p-ANCA were detected whereby colonic
      involvement and extraintestinal manifestations seemed to be important. There was
      no correlation to therapy, activity, sex, age, extent and duration of disease.
      Moreover, the sera did not exhibit significant reactivity in ELISAs testing for
      Cathepsin G-, Lactoferrin-, Myeloperoxidase-, Elastase- or Proteinase 3-
      specificity.

PMID- 8296671
TI  - Lactoferrin, anti-lactoferrin antibodies and inflammatory disease.
AB  - The nucleophilic properties of human lactoferrin (Lf) were demonstrated by
      immunofluorescence microscopy using cryostat rat tissue sections, and the
      nuclear/perinuclear distribution of Lf in ethanol-fixed human neutrophils was
      visualized with rabbit anti-human Lf, producing a P-ANCA/GS-ANA staining pattern.
      Prevention of complement activation by Lf was confirmed in a haemolytic assay.
      Antibodies (IgG) against human Lf were studied by ELISA in sera from patients
      with Crohn's disease, ulcerative colitis, primary sclerosing cholangitis,
      rheumatoid arthritis, systemic lupus erythematous and primary Sjogren's syndrome.
      Anti-Lf antibodies were found in high frequency in ulcerative colitis and primary
      sclerosing cholangitis, but only occasionally in the other conditions.

PMID- 8296672
TI  - Detection of antineutrophil cytoplasmatic antibodies (ANCA) and their association
      with other autoantibodies in patients with hepatobiliary disorders.
AB  - Sera from 35 out of 655 patients with suspected or confirmed hepatobiliary
      diseases were positive for anti-neutrophil antibodies with a perinuclear staining
      pattern (p-ANCA). Nineteen of these sera did not react with myeloperoxidase
      (MPO), Cathepsin G or Elastase, the three proposed antigens of p-ANCAs. No
      distinct antigen for these sera could be characterized by western blot techniques
      with fractionated granulocyte proteins.

PMID- 8296673
TI  - Anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver disease.
AB  - ANCA were detected in 67% of sera from patients with primary sclerosing
      cholangitis (n = 15), in 83% of sera from patients with autoimmune chronic active
      hepatitis (n = 18) and in 35% of sera from patients with primary biliary
      cirrhosis (n = 20). ANCA were not detected in non-autoimmune chronic liver
      diseases. Characterization studies of the antigens involved showed that ANCA in
      autoimmune liver disease are not directed against myeloperoxidase (mpo),
      proteinase 3 (pr3) or elastase (hle), but the ANCA in autoimmune liver disease
      show reactivity with lactoferrin, a 67/66 kD protein combination or a 63/54 kD
      protein combination on Western Blots.

PMID- 8296674
TI  - Proteinase 3: substrate specificity and possible pathogenetic effect of Wegener's
      granulomatosis autoantibodies (c-ANCA) by dysregulation of the enzyme.
AB  - Reactivity of proteinase 3 (PR3) was tested against various amino acid and
      thioester substrates. The best substrate is Boc-Ala-Ala-Nva-SBzl with a kcat/Km
      value of 1.0 x 10(6) M-1.s-1. We also studied the effect of C-ANCA on PR3
      proteolytic activity towards elastin and inactivation by alpha 1-antitrypsin
      (alpha 1AT). C-ANCA IgG from 8 patients with active Wegener's granulomatosis were
      tested and found to inhibit elastin degradation by PR3 and to prevent the
      inactivation of PR3 by alpha 1AT.

PMID- 8296675
TI  - Inhibition of proteinase 3 activity by peptides derived from human epidermis.
AB  - Elafin and antileukoprotease are potent peptide-like inhibitors of human
      leukocyte elastase and have been isolated from human skin and bronchial mucus.
      Elafin proved to be a potent inhibitor of proteinase 3, whereas other inhibitors
      of human leukocyte elastase such as antileukoprotease and eglin C proved to be
      much less effective.

PMID- 8296676
TI  - Implications of c-ANCA testing for the classification of Wegener's
      granulomatosis: performance of different detection systems.

PMID- 8296677
TI  - Pathogenic potential of anti-neutrophil cytoplasmic autoantibodies.

PMID- 8296678
TI  - ANCA and IgG subclasses.
AB  - We studied IgG subclass distribution of ANCA in 247 patients with ELISA. We used
      monoclonal subclass specific antibodies and purified MPO and proteinase 3 as
      antigen. We found that IgG1 and IgG4 yield high values in both groups. We also
      found that high IgG2 titers were rare among the anti-proteinase 3 positive, while
      it was common among anti-MPO sera. In the assays for IgG3 the situation was the
      opposite.

PMID- 8296679
TI  - Anti-MPO antibody (Id) and autoantibody to purified anti-MPO F(ab)2 (anti-Id).

PMID- 8296680
TI  - Cross-reactivity between antibodies to thyroid microsomal antigens and
      myeloperoxidase.
AB  - Antibodies against thyroid microsomal antigen (thyroid peroxidase, TMA/TPO) and
      myeloperoxidase (MPO) were measured from 115 patients with vasculitic disorders
      and 144 patients with suspected thyroid disorders. Nineteen patients, three with
      vasculitis and 16 with thyroid disorders, were shown to have both TPO and MPO
      antibodies, suggesting cross-reactivity of these antibodies. Their cross
      reactivity was further strengthened by studying the capacity of antibodies to
      tolerate dilution in enzyme immunoassay and reactivity with synthetic TPO/MPO
      peptides.

PMID- 8296681
TI  - Pooled human IGG (PHIG) inhibits the binding of anti-myeloperoxidase antibodies
      to myeloperoxidase.
AB  - This study demonstrates that pooled human immunoglobulin (PHIG) contains anti
      idiotypes to anti-myeloperoxidase (MPO) antibodies and can inhibit the binding of
      anti-MPO to MPO. The variability seen in the inhibitory effect of different PHIG
      preparations in the same and also in different patient sera suggests
      heterogeneity in the idiotypic repertoire of anti-MPO antibodies.

PMID- 8296682
TI  - Studies to demonstrate inhibition of functional activity of neutrophil lysosomal
      enzymes with ANCA.
AB  - Many autoantibodies that have enzymes as their targets bind to the catalytic
      sites and inhibit enzymatic activity. We have established functional assays for
      the targets of anti-neutrophil cytoplasm antibodies (ANCA) in order to determine
      whether these antibodies are directed against the corresponding catalytic sites.
      Anti-proteinase 3 activity was measured by the cleavage of alpha-naphthyl
      acetate; myeloperoxidase activity by peroxidation of monochlorodimedon or
      guaiacol using hydrogen peroxide; and elastase activity by a fluorimetric assay
      of the hydrolytic product of N-succ (ala)3 amido-methyl coumarin. The addition of
      immunoglobulin from patients with ANCA to these assays did not result in
      inhibition of functional activity of the corresponding enzyme when compared with
      normal immunoglobulin. Furthermore the removal of specific immunoglobulin by
      solid phase adsorption to the corresponding antigen did not result in an increase
      in enzymatic activity compared with the starting material. However preliminary
      results suggest that anti-neutrophil proteinase 3 binding may be inhibited in a
      solid-phase ELISA by preincubation with a peptide corresponding to the catalytic
      site.

PMID- 8296683
TI  - Down-staging prostate cancer. Is it possible by androgen depletion and Mitomycin
      C therapy?
AB  - The study was carried out in order to investigate the possibility of tumor
      reduction in prostate cancer patients. As a reduction of the primary tumor was
      observed with hormonal treatment and complete response of soft tissue tumor
      markers with Mitomycin C, this combined treatment was given in seven patients to
      evaluate if it was able to down-stage those cases which were thought to be
      incurable (T3N1-2M0/T4N0-2M0). Although the clinical evaluation suggested a
      significant down-staging, the explorative lymphadenectomy was unable to confirm
      this. The proposed treatment is able to reduce the tumor bulk significantly of
      the primary cancer as well as of its metastases; progression during the treatment
      was not seen.

PMID- 8296684
TI  - Pathologic response and long term results of preoperative M-VAC regimen in
      regionally advanced transitional cell carcinoma of the bladder.
AB  - Patients with tumor extending through the bladder wall with invasion of adjacent
      structures or lymph node metastases are seldom cured by radical surgery.
      Preoperative chemotherapy was given to 17 patients with T3-T4, N0, N+ tumor to
      assess operability and long-term survival. Tumor downstaging (T0, Ta, T1, CIS,
      N0) occurred in 4 (80%) of the 5 T3 patients, and in 3 (25%) of the 12 patients
      with T4 tumors. All patients have been followed until death or for a minimum of
      42 months (mean: 56 months, range 42 to 78 months). Surgery was possible in all
      patients. Long-term survival is realized in only 30%, suggesting that this
      approach did not alter the ultimate course of the natural history of the disease.
      Although local recurrence did not occur, 70% of the patients with downstaged
      cancers developed distant metastases.

PMID- 8296685
TI  - [Sympathetic evoked potentials of the perineum].
AB  - The authors describe the principles and indications of sympathetic evoked
      potentials recorded from the pelvic floor. The technique consists of an
      electrical stimulation of a somatic nerve (median nerve at the wrist or dorsal
      nerve of penis) with recording of the electrical activity induced by the
      sympathetic nerve terminals of the sweat glands from the perineal skin, using
      surface electrodes.

PMID- 8296686
TI  - Autosomal dominant polycystic kidney disease in the first year of life. Report of
      a case with no family history.
AB  - Autosomal recessive polycystic kidney disease (RPKD) (also called infantile
      polycystic kidney disease) and autosomal dominant polycystic kidney disease
      (DPKD) (or adult form) are the two main types of genetic polycystic kidney
      diseases (PKD) encountered in children and infants. We report here a case of DPKD
      with no family history and discuss the main features leading to the differential
      diagnosis between these two types of PKD, their prognosis and the importance of
      making the right diagnosis for the genetic counselling.

PMID- 8296687
TI  - [A case of seminoma in a child].

PMID- 8296688
TI  - [Retrocaval ureter (apropos of a case)].
AB  - The authors are reporting a case of lumbar pain secondary to a retrocaval ureter.
      Pathogeny, diagnostic implications and treatment of this entity is discussed.

PMID- 8296689
TI  - Urinary retention due to urethral metastases from rectal adenocarcinoma.

PMID- 8296690
TI  - Intravascular ultrasound versus angiography for measurement of luminal diameters
      in normal and diseased coronary arteries.
AB  - Quantitation of coronary luminal diameter with a 20 MHz mechanically rotating
      intravascular ultrasound (IVUS) catheter was compared with orthogonal-view
      cineangiography by use of a semiautomated edge-detection algorithm in 48 patients
      undergoing coronary angioplasty. Quantitative comparison of 196 matched segments
      was attempted, but in only 174 (88.8%) was a direct comparison of the two
      techniques possible. In angiographically normal coronary arteries (46 segments)
      the correlation between the values obtained by quantitative coronary angiography
      (QCA) and those achieved by IVUS was excellent (r = 0.92, p < 0.0001). For mild
      stenoses (80 segments) the correlation coefficient was only fair (r = 0.467, p <
      0.001). After percutaneous transluminal coronary angioplasty the correlation
      coefficient between IVUS and QCA data (48 segments) was very weak (r = 0.282, p <
      0.05). In conclusion, coronary IVUS is feasible and safe and even for a limited
      range of coronary arterial narrowing, significant correlations between IVUS and
      QCA measurements of minimal lumen diameter were found. They were excellent in
      normal coronary arteries, moderate in mildly diseased arteries, and weak after
      balloon angioplasty.

PMID- 8296691
TI  - Restoration of coronary blood flow in severely narrowed and chronically occluded
      coronary arteries before and after angioplasty: implications regarding
      restenosis.
AB  - The restenosis rate after recanalization of chronic totally occluded coronary
      arteries is high. This may be due to a competitive flow or a low coronary flow
      velocity. This study was designed to assess differences in coronary blood flow
      velocity between severely narrowed and occluded arteries before and after
      successful percutaneous transluminal coronary angioplasty. Thirty-five patients
      were studied including 12 with an occluded vessel (group 1) and 23 with a
      stenosis (group 2). Rest and peak hyperemic (papaverine) coronary blood flow
      velocities were measured. Before successful percutaneous transluminal coronary
      angioplasty, velocity was lower in occlusions than in stenoses (3.8 +/- 2.1 vs
      7.9 +/- 4.8 cm/sec; p < 0.02), whereas resistance was higher (31.7 +/- 20.8 vs
      13.7 +/- 7.0 mm hg/cm/sec, respectively; p = 0.0009). There was no significant
      difference in vasodilator reserve between the two groups. After successful
      percutaneous transluminal coronary angioplasty, the velocity increased in both
      groups and the resistance index decreased. Velocity and resistance were similar
      in the two groups. The vasodilator reserve did not change after the procedure. It
      was concluded that the coronary flow velocity achieved after successful
      recanalization of chronic totally occluded arteries is similar to that observed
      after dilation of stenoses. These results do not support the hypothesis that the
      high rate of restenosis in recanalized chronically occluded vessels is due to
      differences in post-percutaneous transluminal coronary angioplasty blood flow
      velocity.

PMID- 8296692
TI  - Complications and follow-up after intracoronary stenting: critical analysis of a
      6-year single-center experience.
AB  - From April 1986 through April 1992, 123 patients received 153 intracoronary
      stents (131 Medinvent, 13 Palmaz-Schatz, 9 Wiktor) during 131 procedures. The
      indication was bail-out treatment in 39, restenosis in 59 native coronary
      arteries, and stenosis or restenosis in 33 vein grafts. Stent-related events were
      studied during the in-hospital stay and on follow-up and included closure, stent
      restenosis, myocardial infarction, death, and the need for coronary bypass
      surgery. A Kaplan-Meier estimate extended to 6 years showed different short- and
      long-term outcomes for the distinct treatment groups (p < 0.05): right coronary
      artery stenting (more particularly, stenting for restenosis after angioplasty)
      had the lowest and vein graft stenting had the highest stent-related complication
      rate. The complication rate was similar (p > 0.25) (1) in the case of multiple
      nontandem stent implantation during the same procedure; (2) for the different
      endoprosthesis sizes; and (3) during the different procedural years. In native
      coronary arteries, restenosis after angioplasty of the right coronary artery
      could be a preferential indication for coronary artery stenting. Despite a
      favorable short-term outcome, vein graft stenting has a high incidence of events
      on long-term follow-up, mainly because of late restenosis. Multiple nontandem
      stenting during the same procedure is not associated with a higher incidence of
      complications, in particular, the restenosis rate is not appreciably higher.
      Finally, only a minor benefit for the learning curve is apparent from this single
      center experience with continual unchanged postprocedural management.

PMID- 8296693
TI  - Stenting or balloon angioplasty of stenosed autologous saphenous vein grafts in
      pigs.
AB  - In a model of early and aggressive vein graft stenosis in pigs, an intervention
      was performed with a single stent (n = 12 grafts), multiple stents (n = 6), or
      balloon angioplasty (n = 6), while grafts with mild stenoses were left untreated
      (n = 8). Four weeks after intervention, angiography showed that grafts with
      single stents, balloon angioplasty, or untreated grafts had patency rates of 92%,
      83%, and 83%, respectively. Grafts receiving multiple stents, however, showed
      only a 17% patency rate (p < 0.05). Balloon dilatation or placement of a single
      stent improved the angiographic minimal diameter by 0.6 +/- 0.2 and 0.8 +/- 0.3
      mm, respectively, over the short term, but this gain was lost during the follow
      up period. Multiple stents showed a similar gain (0.5 +/- 0.2 mm) but more loss
      occurred during the follow-up period (2.4 +/- 0.2 mm). Histology revealed no
      significant differences between the treatment groups except for the prolonged
      presence of thrombus remnants in association with the stent wires. In conclusion,
      single stents and balloon angioplasty show good patency in early saphenous vein
      graft narrowing but multiple stents show a high occlusion rate.

PMID- 8296694
TI  - Temporal relationship of complications after coronary artery bypass graft
      surgery: scheduling for safe discharge.
AB  - The postoperative courses of 224 patients who left the operating room alive after
      coronary bypass surgery were followed to determine the time of onset of
      complications to determine when discharge is safe. A total of 155 complications
      occurred in 103 patients including 59 with supraventricular tachycardia, 17 with
      fever, and 9 to 11 with ventricular arrhythmias, cerebrovascular accidents, wound
      infection, or deep vein thrombosis. Pneumonia occurred in seven patients, and
      other complications occurred in five or fewer patients. Most initial
      complications (77.6%) occurred by day 5, and 89.3% of the patients with
      complications had their initial event before day 8. Hence it appears that it is
      safe to discharge patients on day 8 after coronary artery bypass graft surgery if
      they have not had a postoperative complication.

PMID- 8296695
TI  - Continuing differences in the rates of percutaneous transluminal coronary
      angioplasty and coronary artery bypass graft surgery between elderly black and
      white Medicare beneficiaries.
AB  - Rates of hospitalization among black and white male and female Medicare
      beneficiaries, 65 years of age and older, for percutaneous transluminal coronary
      angioplasty (PTCA) and coronary artery bypass graft (CABG) surgery and 30-day
      postadmission mortality rates were compared for the years 1986 through 1990. The
      age-adjusted rates of hospitalization for both procedures increased, and the 30
      day postadmission mortality rates decreased in all four race-sex groups. The
      greatest increase in the procedure rates were seen among white males. Using two
      estimates of the prevalence of ischemic heart disease in the elderly to adjust
      for the need for these cardiac procedures, the 1990 rates of PTCA in white
      beneficiaries were between 1.55 and 1.99 times higher than the rates among black
      beneficiaries, and the rates of CABG surgery were between 1.68 and 2.16 times
      higher. These differences in revascularization rates raise questions about
      whether there is equal access to certain treatments in the two race groups.

PMID- 8296696
TI  - Population selection and performance of the exercise ECG for the identification
      of coronary artery disease.
AB  - To quantify the effect of population selection on the performance of exercise ECG
      criteria for the detection of coronary artery disease, the exercise ECGs of 212
      clinically normal nonvolunteer subjects, 31 patients with no significant coronary
      disease at angiography, 153 patients with clinically stable angina, and 184
      patients with catheterization-proved coronary disease were examined. Test
      specificity was examined separately in clinically normal subjects and in patients
      with angiographically normal coronary arteries, and test sensitivity was
      determined separately in patients with stable angina and those with
      catheterization-proved disease. Definition and selection of normal and abnormal
      study populations had marked effects on test performance. Standard ECG criteria,
      a simple ST depression magnitude partition of 150 microV, an ST segment/heart
      rate (ST/HR) index partition of 1.60 microV/beat/min, and an ST/HR slope
      partition of 2.40 microV/beat/min, identified coronary disease with comparably
      high specificities (94% to 97%) in clinically normal subjects, but with
      significantly lower specificities (68% to 77%, p = 0.002 to 0.0001) in patients
      with angiographically normal coronary arteries. Although sensitivity was
      significantly lower in patients with stable angina than in patients with
      catheterization-proved coronary disease for standard criteria (54% vs 70%, p =
      0.004) and for the ST/HR index (88% vs 95%, p = 0.04), there was no significant
      difference in the poor sensitivity of the simple ST depression magnitude criteria
      (51% vs 58%) or in the high sensitivity of the ST/HR slope (93% vs 96%) in these
      abnormal patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296697
TI  - ST-segment depression during adenosine infusion as a predictor of myocardial
      ischemia.
AB  - The incidence and hemodynamic changes associated with ST-segment depression
      during adenosine stress testing are poorly defined. To examine this, 550
      consecutive patients who underwent adenosine perfusion testing were evaluated for
      the development of ST-segment depression. At least 1 mm of horizontal or
      downsloping depression developed in 82 patients (15.9%) and was observed with
      similar frequency in patients with normal scans and those with only fixed
      defects. ST depression developed in 58 of 242 patients with reversible defects
      (sensitivity = 24%) and in only 24 of 275 patients without reversible defects
      (specificity = 91%). Its presence was highly predictive of reversible perfusion
      defects (predictive accuracy = 71%). Similar findings were observed in patients
      with and without ECG evidence of left ventricular hypertrophy. Patients with ST
      depression had perfusion defects in more vessel distributions, had more severe
      defects, and had a greater increase in heart rate during adenosine infusion. Thus
      ST-segment depression occurs infrequently during adenosine infusion but is
      specific for and predictive of myocardial ischemia, as evidenced by reversible
      perfusion scan defects. Patients with ST depression have more severe disease and
      develop faster heart rates during infusion, which could result in decreased
      coronary perfusion during diastole allowing for the development of myocardial
      ischemia.

PMID- 8296698
TI  - Investigation of therapeutic mechanisms of atenolol and diltiazem in patients
      with variable-threshold angina.
AB  - The effects of beta-adrenoreceptor and calcium channel-blocking agents on the
      balance of myocardial oxygen supply and demand were studied in 15 patients (2
      women and 13 men), aged 46 to 69 (mean 62) years, with variable-threshold angina.
      An exercise test was performed before therapy was begun, and 24-hour ambulatory
      ECG monitoring was performed after 1 week of long-acting nitrate therapy, in the
      third week after random assignment to either atenolol or diltiazem, and in the
      third week after crossover. All exercise tests were positive except in one
      patient taking diltiazem. The exercise time to 0.1 mV ST change was 4.2 +/- 1.7
      minutes with no therapy, 5.1 +/- 1.6 minutes with nitrates, 6.6 +/- 0.8 minutes
      with diltiazem, and 6.5 +/- 2.1 minutes with atenolol. The rate-pressure product
      at 0.1 mV ST change was 20.9 +/- 4.6 with no therapy and 21.2 +/- 5.7 and 22 +/-
      4.6 with nitrates and diltiazem, respectively, but fell to 15 +/- 3.9 beats.min.
      1 mm Hg 10(-3) after atenolol (p < 0.01). There was no significant difference in
      the number of anginal attacks or in nitroglycerin consumption per week. The heart
      rate at the onset of ST-segment change during the exercise test and during
      ambulatory ECG monitoring was significantly lower during atenolol than during
      diltiazem treatment. Both atenolol and diltiazem were of similar efficacy in
      increasing nonischemic exercise duration in patients with variable-threshold
      angina and acted primarily by slowing the resting heart rate.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8296699
TI  - Effect of epinephrine treatment during late ischemia and early reperfusion on
      regional myocardial function and infarct size in partially infarcted reperfused
      porcine hearts.
AB  - This study investigated whether epinephrine treatment during late ischemia and
      early reperfusion improves systolic shortening after 45 minutes of reperfusion at
      the cost of increased infarct size. A model consisting of both stunned and dead
      myocytes was used. The left anterior descending coronary arteries of 10 control
      and 10 treated pigs were occluded distally for 40 minutes and then reperfused for
      3 days. Regional systolic shortening was determined by sonomicrometry, and
      infarct size was assessed as the percentage of infarcted (tetrazolium stain) to
      ischemic (dye technique) myocardium. Intravenous administration of epinephrine
      was started 10 minutes before the onset of reperfusion (5 micrograms/min) and
      continued until 45 minutes of reperfusion (mean 18 micrograms/min). Immediately
      before and during 45 minutes of reperfusion, left ventricular peak pressure,
      dp/dtmax, and heart rate were significantly increased in the treated animals.
      After 45 minutes of reperfusion, epinephrine treatment improved systolic
      shortening of the reperfused myocardium (treated group 9% +/- 8%; control group 
      1% +/- 6%; p < 0.01). Transient beta-adrenergic stimulation of the reperfused
      myocardium did not increase infarct size (treated group 57.2% +/- 19%; control
      group 55.4% +/- 17%). In conclusion, epinephrine treatment during late ischemia
      and early reperfusion improved systolic shortening after 45 minutes of
      reperfusion without affecting infarct size.

PMID- 8296700
TI  - Phenylephrine plus propranolol improves the balance between myocardial oxygen
      supply and demand during experimental cardiopulmonary resuscitation.
AB  - Epinephrine increases coronary blood flow but may not improve the balance between
      myocardial oxygen supply and demand during cardiopulmonary resuscitation (CPR).
      The objective of this study was to determine whether this balance can be improved
      by administering a relatively pure alpha-adrenergic vasoconstrictor, alone or in
      combination with a beta-adrenergic blocker. We measured coronary perfusion
      pressures during CPR and myocardial adenosine 5'-triphosphate (ATP) and lactate
      concentrations in biopsies obtained immediately after 10 minutes of CPR in six
      control dogs and in three groups of six dogs each given large doses of
      epinephrine, phenylephrine, or phenylephrine plus propranolol during CPR.
      Coronary perfusion pressure during CPR was higher in the three treated groups
      than in the control group, although differences were limited to the early portion
      of CPR in dogs given epinephrine or phenylephrine alone. Postresuscitation
      myocardial ATP concentration was significantly higher (29.5 +/- 3.0 vs 22.6 +/-
      1.8 nmol/mg of protein, p < 0.05) and myocardial lactate concentration tended to
      be lower (52.8 +/- 13.6 vs 78.5 +/- 15.2 nmol/mg of protein) than in the control
      group in dogs given both phenylephrine and propranolol. In contrast, myocardial
      ATP concentration tended to be lower than in the control group in epinephrine
      treated dogs, and myocardial lactate concentrations were higher than in the
      control group in dogs treated with either epinephrine (p < 0.05) or phenylephrine
      alone (p = 0.052). We conclude that the balance between myocardial oxygen supply
      and demand during CPR can be improved by administering a combination of
      phenylephrine and propranolol, but not by administering large doses of
      epinephrine or phenylephrine alone.

PMID- 8296701
TI  - Effect of pravastatin treatment on glucose, insulin, and lipoprotein metabolism
      in patients with hypercholesterolemia.
AB  - Treatment of patients with type IIA hyperlipoproteinemia (HLP) with pravastatin
      for 3 months led to significant decreases (p < 0.001) in total cholesterol (7.18
      +/- 0.30 to 5.75 +/- 0.30 mmol/L), LDL cholesterol (5.56 +/- 0.33 to 4.02 +/-
      0.32 mmol/L), and ratio of total cholesterol to HDL cholesterol (6.5 +/- 0.4 to
      4.6 +/- 0.4). Decreases of a similar magnitude were also seen in patients with
      type IIB HLP. Plasma glucose and insulin concentrations after an oral glucose
      load and from 8 AM to 4PM in response to meals were higher in patients with Type
      IIB HLP, who also had higher steady-state plasma glucose concentrations after an
      infusion of somatostatin, insulin, and glucose (12.4 +/- 1 vs 5.5 +/- 0.8 mmol/L,
      p < 0.001). Because steady-state plasma insulin concentrations were similar in
      both groups, patients with type IIB HLP were relatively insulin resistant.
      Furthermore, day-long plasma glucose concentrations and insulin resistance were
      modestly, but significantly (p < 0.01), greater after treatment in both groups.
      In conclusion, LDL cholesterol metabolism improved in hypercholesterolemic
      subjects treated with pravastatin, but the hypertriglyceridemia, insulin
      resistance, relative glucose intolerance, and hyperinsulinemia present in
      patients with type IIB HLP either did not improve with treatment or was somewhat
      worse.

PMID- 8296702
TI  - Evaluation of thoracic aortic atherosclerosis by transesophageal
      echocardiography.
AB  - Transesophageal echocardiography (TEE) provides excellent images of the thoracic
      aorta, which cannot be visualized by transthoracic echocardiography. The purpose
      of this study was to assess atherosis and sclerosis of the thoracic aorta by TEE,
      to evaluate the risk factors for atherosis and sclerosis, and to assess the
      relationship between the two components of atherosclerosis. The mean value of the
      maximum thickness of the intima-media complex in the six segments of the thoracic
      aorta (MIMC) was used as an index of atherosis, and the stiffness parameter beta
      was used as an index of sclerosis. The study population consisted of 88 Japanese
      patients. Multivariate analysis showed that age, low-density lipoprotein
      cholesterol (or apolipoprotein B), and diabetes mellitus were significantly and
      independently related to MIMC, whereas age and hypertension were related to the
      stiffness parameter beta. Both components of atherosclerosis demonstrated a
      significant although weak relationship. The risk factors for atherosis appear to
      differ from those for sclerosis in the thoracic aorta, so we should evaluate
      these two components of atherosclerosis separately. TEE is a useful method of
      assessing thoracic aortic atherosclerosis because both atherosis and sclerosis
      can be examined simultaneously.

PMID- 8296703
TI  - Slow abnormal conduction in the low right atrium: its anatomic basis and
      relevance to atrial reentry.
AB  - To characterize slow abnormal conduction in the low right atrium, which is known
      to be responsible for atrial flutter, electrophysiologic findings were correlated
      with anatomic features in a canine model of atrial flutter with ligation of the
      crista terminalis in the midright atrium. Activation in the low right atrium was
      mapped with a patch electrode containing 52 bipolar electrodes and a multiplexing
      system. A particular region in the low right atrium showed atrioventricular node
      like electrophysiologic properties, a rate-dependent conduction delay, and
      Wenckebach periodicity. This area coincided with an area responsible for slow
      conduction during atrial flutter and unidirectional block at its initiation. Both
      pilsicainide and E-4031 preferentially blocked conduction in the specific area,
      leading to the termination of atrial flutter. Although refractoriness could not
      explain the abnormal conduction, anatomic studies consistently found the specific
      region to be in or around a thick muscle bundle, that is, the crista terminalis,
      or a thick pectinate muscle branching from the crista, located perpendicular to
      the wavefront of the pacing impulse and atrial flutter. These electrophysiologic
      and anatomic findings suggest that slow abnormal and atrioventricular node-like
      conduction over a thick muscle bundle, which is a normal anatomic feature of the
      low right atrium, plays a role in the initiation, maintenance, and termination of
      atrial reentry.

PMID- 8296704
TI  - Ventricular tachycardias of right ventricular origin: markers of subclinical
      right ventricular disease.
AB  - The diagnosis of subclinical myocardial disease in patients with ventricular
      tachycardias of right ventricular (RV) origin and no overt cardiac abnormalities
      is important, inasmuch as the presence of RV cardiomyopathy or arrhythmogenic
      dysplasia can be associated with a poor prognosis. To this end the relative value
      of symptoms, ECG features of ventricular tachycardia, signal-averaged ECGs, and
      RV echocardiograms as compared with endomyocardial biopsy findings was
      prospectively evaluated. Twenty-seven patients with chronic ventricular
      tachycardias with a left bundle branch block-like morphology, presumed to be of
      RV origin, were studied. Clinical examination findings, 12-lead ECGs in sinus
      rhythm, radiographs of the chest, coronary angiograms, and left ventricular
      cineangiograms were normal in all patients. RV biopsies were abnormal in 11
      patients (41%) with findings suggestive of RV dysplasia or cardiomyopathy. A
      multivariate analysis showed a significant correlation between an abnormal biopsy
      and sustained ventricular tachycardia (p < 0.05), tachycardia with a superior
      frontal plane axis (p < 0.001), an abnormal signal-averaged ECG (p < 0.05), and
      an abnormal RV echocardiogram (p < 0.001). An abnormal RV echocardiogram was both
      a sensitive (73%) and a specific (94%) indicator of an abnormal RV biopsy.
      Sustained tachycardia although sensitive (90%) had a low specificity (56%). In
      comparison, a superior frontal plane axis of ventricular tachycardia and an
      abnormal signal-averaged ECG were indicative of high specificity and low
      sensitivity for abnormal myocardial histologic findings.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8296705
TI  - Pronounced increase in defibrillation threshold associated with pacing-induced
      cardiomyopathy in the dog.
AB  - Progressive changes in myopathology after implantation of an automatic
      defibrillator could compromise device efficacy. The influence of heart failure
      development on the defibrillation threshold was evaluated by means of a rapid
      ventricular pacing model of heart failure in dogs. After transvenous pacemaker
      lead implantation, adult mongrel dogs were randomly assigned to either the
      control (n = 7) or rapidly paced group (240 beats/min, n = 6). Seventeen days
      after implantation, triplicate determinations of the defibrillation threshold
      were made with three epicardial electrodes. The average defibrillation threshold
      was four times higher in the rapidly paced group, 13.3 +/- 2.0 joules (mean +/-
      SEM), than in the control group, 3.3 +/- 0.7 joules (p < 0.01), and was
      significantly correlated with ventricular weight (r = 0.70, p < 0.01). Both
      defibrillation threshold energy per gram of ventricle and ventricular weight
      corrected for body weight were significantly higher in rapidly paced dogs
      compared with control dogs. It was concluded that myocardial hypertrophy and
      heart failure may profoundly increase defibrillation energy requirements.

PMID- 8296706
TI  - Vasodilatory capacity of coronary resistance vessels in dilated cardiomyopathy.
AB  - Both the endothelium-dependent and endothelium-independent vasodilatory responses
      of coronary resistance vessels were studied in patients with dilated
      cardiomyopathy (DCM). A 3F coronary Doppler catheter was placed in the proximal
      left anterior descending artery in 14 patients with DCM and in 10 patients with
      chest pain syndrome and a normal heart (control subjects). The ratio of maximum
      mean coronary blood flow velocity after intracoronary administration of the
      endothelium-independent vasodilator papaverine (10 mg) to resting mean coronary
      blood flow velocity (Vp/Vo) in patients with DCM was diminished compared with
      that in control subjects (2.2 +/- 0.6 vs 4.1 +/- 0.9, p < 0.001). The ratio after
      administration of the endothelium-dependent vasodilator acetylcholine (40
      micrograms) (Va/Vo) in 10 DCM patients was also diminished compared with that in
      seven control subjects (1.3 +/- 0.5 vs 2.4 +/- 0.8, p < 0.01). In DCM patients,
      Vp/Vo was correlated with left ventricular end-diastolic pressure (r = -0.48, p <
      0.05), left ventricular end-diastolic volume index (r = -0.68, p < 0.01),
      ejection fraction (r = 0.75, p < 0.01), and left ventricular end-diastolic wall
      stress (r = -0.73, p < 0.01). However, Va/Vo was not correlated with any of these
      parameters. These results indicate that impairment of the vasodilatory capacity
      of coronary resistance vessels in DCM may be related to endothelial dysfunction
      and to an extravascular factor resulting from left ventricular dysfunction.

PMID- 8296707
TI  - Relationship between intracellular calcium and oxygen consumption: effects of
      perfusion pressure, extracellular calcium, dobutamine, and nifedipine.
AB  - All of the mechanisms that connect the cardiac mechanical work load with energy
      production have not been clearly defined. The purpose of this study was to
      evaluate the relationship between intracellular calcium and oxygen consumption in
      intact hearts, to further understand this relationship. Intracellular calcium was
      measured in isolated nonworking perfused rat hearts loaded with Indo-1 by means
      of a surface fluorometry technique. Glucose was used as a substrate. Myocardial
      contraction and oxygen consumption were modulated by perfusion pressure (80, 110,
      and 140 cm of water), extracellular calcium (1, 2, 3, and 4 mmol/L), dobutamine
      (10(-6) mol/L), and nifedipine (10(-6) mol/L). With all of these interventions
      there was a close correlation between intracellular calcium (systolic, diastolic,
      and amplitude) and oxygen consumption or left ventricular developed pressure.
      Observations in this study support the hypothesis that intracellular calcium
      plays a regulatory role in the link between cardiac mechanics and energy
      production.

PMID- 8296709
TI  - Antithrombotic therapy in prosthetic heart valve replacement.

PMID- 8296708
TI  - Interaction of intravenous atrial natriuretic factor with furosemide in patients
      with heart failure.
AB  - Furosemide is frequently administered intravenously to patients with chronic
      heart failure. However, use of diuretics may cause neuroendocrine activation and
      by itself may not consistently afford diuresis. Atrial natriuretic factor (ANF)
      in pharmacologic doses is a vasodilator and has favorable neuroendocrinologic
      effects in patients with congestive heart failure. To examine whether exogenous
      ANF might enhance the effects of acute furosemide injection, we studied 14
      patients with chronic stable heart failure and measured the effects of the
      combination of ANF and furosemide on hemodynamics, neuroendocrine activation, and
      urine output. Eight patients were randomly assigned to receive placebo plus
      furosemide (1.3 mg/kg intravenously). Six patients received ANF (2 micrograms/kg
      intravenously) plus furosemide at the same dose in a double-blind manner. The
      group receiving placebo plus furosemide exhibited a slight increase in mean
      arterial pressure (92 to 96 mm Hg; p < 0.03), systemic vascular resistance (1989
      to 2271 dynes.sec.cm-5; p = 0.0007), and pulmonary capillary wedge pressure (22
      to 24 mm Hg; p < 0.04) from baseline to 10 minutes. The group receiving ANF plus
      furosemide exhibited no change in mean arterial pressure and systemic vascular
      resistance from baseline to 10 minutes. Pulmonary capillary wedge pressure and
      mean pulmonary pressure were unchanged. In the group receiving placebo plus
      furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296710
TI  - Interposed abdominal compression as an adjunct to cardiopulmonary resuscitation.
AB  - The addition of IAC to otherwise standard CPR provides for the application of
      external pressure over the abdomen in counterpoint to the rhythm of chest
      compression. Interposed abdominal compression is a simple manual technique that
      can supplement the use of adrenergic drugs to increase both coronary perfusion
      pressure and total blood flow during CPR. Mechanistically, manual abdominal
      compressions induce both central aortic and central venous pressure pulses.
      However, owing to differences in venous versus arterial capacitance, the former
      are usually greater than the latter, so that systemic perfusion pressure is
      enhanced. Moreover, practical experience and theoretical analysis have suggested
      subtle refinements in the hand position and technique for abdominal compression
      that may further improve the ratio of arterial to venous pressure augmentation.
      Clinical studies confirm that IAC-CPR can improve perfusion pressures and carbon
      dioxide excretion during CPR in humans. The incidence of abdominal trauma,
      regurgitation, or other complications is not increased by IAC. Recently,
      randomized trials have shown that short-term and long-term survival of patients
      resuscitated in the hospital by IAC-CPR are about twice that of control patients
      resuscitated by standard CPR. The technique of IAC has thus evolved to become a
      highly promising adjunct to normal CPR, which is likely to be implemented in an
      increasing number of clinical protocols in the 1990s.

PMID- 8296712
TI  - Dual-balloon progressive coronary dilatation catheter: design and initial
      clinical experience.
AB  - As newer interventional devices continue to enter the marketplace, balloon
      angioplasty remains the standard by which all devices are judged with regard to
      both safety and efficacy. It has been observed that predilating a stenosis with a
      small balloon followed by dilatation with an optimally sized larger balloon
      creates a more controlled arterial injury, reduces complications, and thus
      improves success rates. Exchanging two balloons for each lesion, however,
      increases the complexity and cost of the procedure in addition to increasing the
      amount of time required and the amount of radiation exposure. Therefore an "over
      the-wire" dual-balloon catheter was developed with a small distal balloon and a
      larger proximal balloon on a 2.9F shaft to allow progressive coronary dilatation
      with a single device, without necessitating a balloon catheter exchange. The
      device was used successfully in 45 of 47 patients (78 lesions). The two failures
      were related to an inability to cross the lesion in one and failure of the device
      in the other. Twenty-one patients (47%) underwent a multivessel procedure. There
      were 29 left anterior descending/diagonal, 17 circumflex/marginal, 20 right
      coronary artery/posterior descending artery, and 10 vein graft lesions. The
      device was successfully delivered in the native anatomy to 12 distal, 27 mid, and
      27, proximal lesions of which nine were osteal, for a procedural success rate of
      97%. The mean stenosis was reduced from 80.7 +/- 11.5% to 15.2 +/- 11.9%. There
      were no major dissections, only 9 (11.2%) minor dissections, and no myocardial
      infarctions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296711
TI  - Coronary calcium and atherosclerosis by ultrafast computed tomography in
      asymptomatic men and women: relation to age and risk factors.
AB  - We evaluated 675 men and 190 women who had no symptoms or history of clinical
      CHD, to determine the prevalence and risk factor correlates of CAC deposits as a
      marker of atherosclerosis. Measurements were taken noninvasively by ultrafast CT.
      The presence and extent of CAC deposits as measured by ultrafast CT was
      determined in all subjects, who also received personal and family medical history
      and risk factor questionnaire. The prevalence of CAC deposits increased
      significantly with age, ranging from 15% and 30% in men and women, respectively,
      < 40 years of age to 93% and 75% in those aged > or = 70 years. Prevalence and
      total score also increased by the number of risk factors present, although in
      those aged > 60 years a high prevalence (> 80% in men) of calcium was present
      regardless of the presence of risk factors. In multiple logistic regression, age,
      male gender, hypertension, diabetes, hypercholesterolemia, and obesity were
      independently associated with CAC deposits. These results suggest a high
      prevalence of atherosclerosis with increasing age and the presence of risk
      factors in men and women who have no symptoms. Studies to determine the
      prognostic value of CAC in individuals with no symptoms are needed to determine
      which populations may benefit most from CAC deposit screening.

PMID- 8296713
TI  - Coronary flow velocity monitoring after angioplasty associated with abrupt
      reocclusion.

PMID- 8296714
TI  - Transthoracic two-dimensional and color flow echocardiographic diagnosis of
      aberrant left coronary artery.

PMID- 8296715
TI  - Coronary artery aneurysm masquerading as a paracardiac mass on transesophageal
      echocardiography.

PMID- 8296716
TI  - Papillary fibroelastoma of the aortic valve with myocardial infarction:
      echocardiographic diagnosis and surgical excision.

PMID- 8296717
TI  - Transesophageal echocardiographic detection of multiple mitral valve masses in
      primary antiphospholipid syndrome with stroke.

PMID- 8296718
TI  - Prosthetic mitral valve thrombosis in pregnancy successfully treated with
      streptokinase.

PMID- 8296719
TI  - Balloon valvotomy for severe aortic stenosis with congestive heart failure in
      adolescents.

PMID- 8296720
TI  - Double aortic arch and bilateral patent ducti arteriosi associated with
      transposition of the great arteries: missing clinical link in an embryologic
      theory.

PMID- 8296721
TI  - Primary pericardial sarcoma.

PMID- 8296722
TI  - White blood cell count and insulin resistance in healthy nonsmoking men.

PMID- 8296723
TI  - Massive left atrial calcification: a limitation of transesophageal
      echocardiography.

PMID- 8296724
TI  - Intracardiac rheumatoid nodule presenting as a left atrial mass.

PMID- 8296725
TI  - Mediastinal chloroma affecting the right heart with superior vena cava syndrome.

PMID- 8296726
TI  - Sunray appearance on enhanced magnetic resonance image of cardiac angiosarcoma
      with pericardial obliteration.

PMID- 8296727
TI  - Current treatment options for paroxysmal supraventricular tachycardia.

PMID- 8296728
TI  - Should implantable cardioverter-defibrillators be activated immediately after
      implantation?

PMID- 8296729
TI  - Frequency of repeat coronary bypass or coronary angioplasty after coronary artery
      bypass surgery using saphenous venous grafts.
AB  - This study examines the long-term frequency of reoperative coronary artery bypass
      grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) after
      CABG. The source of data was the clinical database at Emory University Hospitals.
      The population comprised 3,480 patients undergoing a first CABG between 1978 and
      1981. Event-free survival was determined using the Kaplan-Meier method and
      determinants of survival with the Cox proportional-hazards model. The in-hospital
      mortality was 1.0% and 5-, 10- and 12-year survival was 91, 78 and 70%. The 5-,
      10- and 12-year freedom from reoperative CABG was 98, 88 and 80%. The  5-, 10-
      and 12-year freedom from PTCA was 98, 91 and 85%. The 5-, 10- and 12-year freedom
      from either CABG or PTCA was 96, 81 and 69%. Younger patients had much higher
      incidences of repeat procedures. The yearly incidence of repeat procedures
      accelerated over time. These data reveal the ultimately palliative nature of
      revascularization for coronary artery disease.

PMID- 8296730
TI  - Comparison of fixed-wire and over-the-wire balloon dilatation systems for
      percutaneous transluminal coronary angioplasty.
AB  - There is controversy concerning the relative safety and efficacy of the 2
      currently available percutaneous transluminal coronary angioplasty dilatation
      systems--fixed-wire (FW) and over-the-wire (OW). A randomized, prospective trial
      comparing the 2 systems was performed to examine this controversy. Of 1,513
      patients undergoing percutaneous transluminal coronary angioplasty at 3 centers
      between June 1990 and October 1991, 602 (40%) fulfilled the eligibility criteria
      for the study. There were 643 lesions, of which 327 were randomized to FW and 316
      to OW systems. There was no difference in the success rate between FW (92%) and
      OW (94%) systems. Inability to cross with a wire was infrequent with either
      system (FW: 1.8%; and OW: 1.6%). Inability to cross with a balloon when the wire
      crossed the lesion did not occur. An FW system was successful in 6 cases (1.9%)
      in which the OW system had been unsuccessful, whereas an OW system succeeded in
      14 (4.3%) after the FW system had been unsuccessful (p = NS). Time to cross
      stenoses was 200 +/- 21 and 233 +/- 22 seconds, procedural time was 21 +/- 1.3
      and 21 +/- 1.0 minutes, fluoroscopy time was 6.7 +/- 0.4 and 7.1 +/- 0.4 minutes,
      contrast used was 89.0 +/- 4.2 and 84.0 +/- 3.5 ml, and number of cine runs was
      5.9 +/- 3.0 and 6.3 +/- 3.4 in the FW and OW systems, respectively. Complications
      were infrequent with either system (FW: 10.4%; and OW: 9.5%). Acute closure
      occurred in 1.8 and 2.2% of cases in the FW and OW systems,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296731
TI  - Effectiveness of holmium laser-assisted coronary angioplasty. The Holmium Laser
      Coronary Registry.
AB  - The efficacy of holmium laser-assisted angioplasty was studied in 365 narrowings
      in 331 consecutive patients with coronary artery disease. Clinical indications
      for study were unstable angina pectoris in 140 patients (42%), stable angina in
      136 patients (41%), postmyocardial infarction angina in 35 patients (10.5%),
      silent myocardial ischemia in 11 patients (3%), acute myocardial infarction in 1
      patient (0.3%) and undefined in 8 patients (2%). Coronary morphology
      characteristics by Multivessel Angioplasty Prognosis Study group criteria were
      type A in 12.6%, type B1 in 34.2%, type B2 in 27.4% and type C in 25.4%. The
      laser successfully crossed the total length of the narrowing in 85.2%. Procedural
      success was 94.2%. Laser alone reduced mean percent luminal narrowing from 88 +/-
      11% to 57 +/- 22%. Subsequent balloon angioplasty further reduced the mean
      luminal narrowing to 23 +/- 18%. Major complication rate was 2.7% (death 0.3%, Q
      wave myocardial infarction 0.5%, and emergent bypass surgery 2.7%). Six-month
      angiographic restenosis (> 50% stenosis) rate was 44%.

PMID- 8296732
TI  - Immediate results of interventional devices for coronary ostial narrowing with
      angina pectoris.
AB  - Angioplasty of aorto-ostial lesions has had suboptimal results. This study
      reports on the immediate results of new debulking devices (atherectomy, excimer
      laser) in the treatment of aorto-ostial disease. Thirty-one vessels (29 patients)
      with an ostial lesion treated with a new device (group I) were compared with 15
      vessels (13 patients) with an ostial lesion treated with angioplasty alone during
      the preceding 24 months (group II). Both groups were similar in their clinical
      characteristics. A larger proportion of vessels in group I (64%) compared with
      group II (7%) had unfavorable features for angioplasty. Procedural success was
      similar: 28 vessels in group I (91%) and 14 in group II (93%). Among the new
      devices, success was also similar: atherectomy in 8 arteries (89%), rotablator in
      4 (100%) and excimer laser in 17 (94%). The acute gain was more significant with
      new devices: absolute reduction in percent stenosis was 66% for directional
      atherectomy, 67% for rotational atherectomy (p = 0.016 compared with
      angioplasty), 52% for excimer laser (p = 0.09) and 46% for angioplasty. In group
      I, 2 patients (6%) required emergency bypass surgery during our early experience;
      no deaths or Q-wave myocardial infarctions occurred. Group II had no
      complications. Therefore in aorto-ostial lesions, despite a much higher
      prevalence of unfavorable angiographic characteristics, new devices had (1) a
      success rate of > or = 90%, (2) a significantly larger acute gain compared with
      angioplasty alone, and (3) an acceptable complication rate. Larger studies with
      complete angiographic follow-up are needed to assess restenosis.

PMID- 8296733
TI  - Feasibility of recanalization of human coronary arteries using high-intensity
      ultrasound.
AB  - To investigate the feasibility of ultrasonic recanalization of obstructed human
      coronary arteries in vitro, high-intensity ultrasound was applied to 16 coronary
      arteries obtained at autopsy, using a prototype instrument enabling
      insonification through a catheter tip. It was a 119 cm long, 0.95 mm thick wire
      in an 8Fr catheter connected to an external ultrasonic transformer and power
      generator. A 5 MHz phased-array 2-dimensional echocardiography instrument was
      used to determine minimal luminal diameter and percent diameter narrowing before
      and after ultrasound application. The ultrasonic energy was delivered at 21.5 kHz
      and with a 52 +/- 19 micrometer average amplitude of tip displacement. The mean
      percent luminal diameter narrowing, flow rate and mean pressure gradient before
      ultrasound exposure were 74 +/- 11%, 97 +/- 61 ml/min, and 92 +/- 18 mm Hg,
      respectively. After recanalization, the mean percent luminal diameter narrowing
      decreased to 45 +/- 17% (p < 0.001), the mean flow rate increased to 84 +/- 92
      ml/min (p < 0.001), and the mean pressure gradient was reduced to 45 +/- 24 mm Hg
      (p < 0.001). Of the debris particles, 95% had a diameter < 9 microns (range 5 to
      12). Arterial perforation occurred in 5 of 16 arteries (31%) and all 5 occurred
      due to stiff wire manipulation and without ultrasound application. Mechanical
      fracture of the wire occurred in 8 cases (50%). No signs of thermal injury were
      found on histology. Thus, ultrasonic recanalization of human coronary arteries in
      vitro is feasible. It may reduce obstruction and improve blood flow. Debris sizes
      are sufficiently small to minimize the hazard of peripheral embolization.

PMID- 8296734
TI  - Prediction of atherosclerotic cardiovascular death in men using a prognostic
      score.
AB  - Treadmill and clinical data were gathered prospectively on consecutive patients
      who underwent exercise testing for evaluation for coronary artery disease in a
      1,200 bed Veterans Affairs Medical Center. From 3,609 men referred for exercise
      testing from 1984 to 1990, 3,134 patients remained after excluding those with
      significant valvular heart disease and those with prior coronary artery bypass
      surgery. Of these, 588 were selected for clinical reasons to undergo cardiac
      catheterization within 3 months of evaluation leaving 2,546 who were not
      selected. Over 3 years, there were 158 cardiovascular deaths, 99 nonfatal
      myocardial infarcts and 183 patients who underwent coronary artery bypass
      surgery. In the total population, the Cox proportional-hazards model demonstrated
      the following characteristics to be statistically significant independent
      predictors of time until cardiovascular death: a history of congestive heart
      failure and/or taking digoxin, exercise-induced ST depression, the change in
      systolic blood pressure during exercise, and exercise capacity in METs. Using the
      Cox model coefficients to weight the variables, a simple score (the Veterans
      Affairs Prognostic Score) was constructed based on these items. Average annual
      cardiovascular mortality was plotted against the score enabling its estimation
      for any given patient. In the subgroup selected for cardiac catheterization (n =
      588), the mean score was greater, consistent with a poorer prognosis, compared
      with the total population; 53% (n = 312) had a score < -2 associated with an
      annual mortality < 2%. Thus, in over half of the patients selected for
      catheterization, the catheterization was unnecessary if performed to lessen their
      chance of cardiovascular death, since no intervention could improve their
      prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296735
TI  - Significance of anterior ST depression in inferior wall acute myocardial
      infarction.
AB  - Early tomographic myocardial perfusion imaging with technetium-99m sestamibi was
      performed during inferior wall acute myocardial infarction to determine the
      relation between the amount and location of myocardium at risk and the presence
      or absence or anterior ST depression. The total size of the acute perfusion
      defect and its lateral and septal borders were measured in 29 consecutive
      patients who were admitted with > 30 minutes of chest pain and acute inferior ST
      elevation on their initial electrocardiogram. The 22 patients with anterior ST
      depression had significantly more left ventricular myocardium at risk than the 19
      patients who did not have anterior ST depression (23 +/- 2% of the left ventricle
      vs 15 +/- 1%, p = 0.008). All 8 patients with > 25% of the left ventricle at risk
      had anterior ST depression. Patients with anterior ST depression had a
      significantly greater lateral extent of the acute perfusion defect (49 degrees +/
      8 degrees from the midinferior wall vs 23 degrees +/- 7 degrees, p = 0.002).
      There was no difference in the septal border of the perfusion defect between
      patients with and without anterior ST depression (-44 degrees +/- 4 degrees vs 
      46 degrees +/- 7 degrees, p = NS). No patient had a measurable anterior perfusion
      defect. Although there is considerable overlap between groups with and without
      anterior ST depression, anterior ST depression is a simple and readily available
      indicator of myocardium at risk in inferior wall acute myocardial infarction.

PMID- 8296736
TI  - Frequency of inclusion of patients with cardiogenic shock in trials of
      thrombolytic therapy.
AB  - The purpose of this study was to determine the extent to which patients with
      cardiogenic shock have participated in trials of thrombolytic therapy, to examine
      factors associated with their exclusion from these trials, and to summarize data
      on the efficacy of thrombolysis in these patients. Previous publications were
      searched for all randomized, controlled studies involving the use of thrombolytic
      medications used in the treatment of acute myocardial infarction. Data were
      abstracted for year of trial publication, performance location, sample size,
      maximal allowable delay between symptom onset and treatment, and exclusion
      criteria. Of the 94 trials included in the analysis, 22% included patients with
      cardiogenic shock, 37% excluded them, and the remainder contained no information
      on their inclusion or exclusion. Only 2 trials provided data on the efficacy of
      thrombolytic therapy in patients with cardiogenic shock. Multivariate analysis
      revealed that studies conducted exclusively in the U.S. were significantly more
      likely to exclude patients in cardiogenic shock than those conducted outside of
      the U.S., as were studies that excluded patients with a previous myocardial
      infarction, studies published more recently, and smaller trials. Patients with
      cardiogenic shock have frequently been excluded from clinical trials of
      thrombolytic agents. As a result, data on the efficacy of thrombolytic agents in
      these patients is extremely limited.

PMID- 8296737
TI  - Long-term prognosis of medically treated patients with acute myocardial
      infarction and one-vessel coronary artery disease.
AB  - Long-term prognosis was studied in 156 patients with acute myocardial infarction
      (AMI) with 1-vessel coronary artery disease (CAD). During a mean follow-up period
      of 110 months, 19 patients (14%) had reinfarction, 15 (9.6%) died (including 7
      deaths of cardiac origin) and 15 (9.6%) were hospitalized for worsening of
      angina. A coronary arteriogram was obtained twice in 54 patients. The coronary
      arteriogram revealed multivessel CAD in all cases with reinfarction (n = 14). Ten
      percent of the patients with multivessel disease experienced a reinfarction
      during the initial 3 years after the onset of the first AMI. The recurrence rate
      of AMI in patients with 1-vessel disease increased gradually from the third year
      after the onset of their first AMI, reaching 10% in 6.7 years. The recurrence of
      AMI at the same region as the original infarction was detected in only 1 patient.
      Six of 19 patients (32%) with recurrence of AMI died and 13 survived after the
      reinfarction. It was difficult to predict future progression from the outcome of
      the comparison between the first and second coronary arteriograms. Thus, in
      patients with uncomplicated AMI with 1-vessel CAD, the prognosis is relatively
      good and the frequency of reinfarction is very low with conservative treatment.

PMID- 8296738
TI  - Exercise testing and training in physically disabled men with clinical evidence
      of coronary artery disease.
AB  - A prospective, randomized, controlled clinical trial in patients with coronary
      artery disease (CAD) and a concurrent physical disability evaluated the effects
      of a home exercise training program on cardiovascular function and blood lipids.
      Eighty-eight men between the ages of 42 and 72 years (mean 62) with documented
      CAD and a physical disability with functional use of > or = 2 extremities
      including 1 arm were randomized to either a 6-month home exercise training
      program using wheelchair ergometry or to a control group that received usual and
      customary care. Both groups received dietary instructions and were requested to
      follow a fat-controlled diet. Exercise test variables with echocardiography and
      blood lipids were measured at baseline and at 6 months. The home exercise
      training group significantly improved both peak exercise left ventricular
      ejection fraction (p = 0.007) and fractional shortening (p = 0.01) between
      baseline to 6 months, whereas the control group showed no significant changes.
      Exercise training effects of decreased resting heart rate (p = 0.03) and
      decreased peak rate pressure product (p = 0.03) were also found in the treatment
      group. No exercise-related cardiac complications occurred. Both groups
      significantly (p < or = 0.01) increased high-density lipoprotein cholesterol
      levels. These results indicate that physically disabled men with CAD can safely
      participate in a home exercise training program which may result in intrinsic
      cardiac benefits. The metabolic cost of activities of daily living imposed on
      this disabled population may also have a positive effect on high-density
      lipoprotein cholesterol levels.

PMID- 8296739
TI  - Frequency and significance of conduction defects early after orthotopic heart
      transplantation.
AB  - To define the clinical significance of conduction defects after orthotopic heart
      transplantation sequential electrocardiograms (ECG) of 124 patients were analyzed
      during their postoperative hospital stay. The first ECG was abnormal in 90
      patients (73%), with a predominance of right bundle branch block, and normal in
      34 (27%). Sex, age, mean donor ischemic time, duration of aortic cross clamping
      and use of previous antiarrhythmic therapy were not significantly different in
      the 2 groups. During hospital follow-up, patients were grouped according to
      evolution of the initial electrocardiographic abnormalities. In group 1, 25
      patients continued to have an initially normal ECG. In groups 2 and 3, 30 and 48
      patients, respectively, had evidence of transient and permanent conduction
      defects. The 21 patients in group 4 showed progressive deterioration of
      conduction with either a new (9 patients) or worsening preexisting conduction
      defect (12 patients). The evolution of the initial ECG was strongly dependent on
      the duration of the donor heart ischemic time and the severity of the in-hospital
      cardiac rejection. Patients with persistent conduction abnormalities had a
      statistically longer ischemic time than either patients with normal or transient
      conduction defects (182 +/- 84 vs 144 +/- 68 and 130 +/- 66 minutes, p = 0.04).
      Although the overall percentage of patients with histologic evidence of moderate
      to severe rejection was similar across the groups, 66.6 and 46.1% of patients in
      groups 3 and 4, respectively, had multiple episodes of rejection compared with
      16.6 and 0% in the remaining 2 groups (p = 0.044).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8296740
TI  - Arterial oxygen saturation in chronic congestive heart failure.
AB  - Continuous, 24-hour, ambulatory pulse oximetry was used in 10 subjects with New
      York Heart Association functional class II to III heart failure and in 5 age
      matched controls to test the prevailing view that arterial oxygen saturation is
      preserved during wakefulness in chronic mild to moderate heart failure. Subjects
      with heart failure were stabilized on digitalis and diuretics at the time of the
      study. All subjects maintained time-activity logs, with an emphasis on self
      reported sleep and wakefulness. A desaturation event was defined as a decrease in
      arterial oxygen saturation > or = 4% from baseline lasting > 5 seconds. Variables
      assessed included total desaturation events, decrease in arterial oxygen
      saturation duration/event, nadir of arterial oxygen saturation/event, and
      desaturation index ([cumulative desaturation time/total monitoring time] x 100).
      The ratio of self-reported wakefulness:sleep desaturation time was 47:53% for
      subjects with heart failure versus 64:36% for controls (p = NS). Mean (+/- SEM)
      time of arterial oxygen saturation < 90% was 123 +/- 67 minutes for subjects with
      heart failure versus 22 +/- 25 minutes for controls (p < 0.01). Total
      desaturations were 220 +/- 63 and 76 +/- 35 (p = NS) for the heart failure and
      control groups, respectively. The heart failure group had a statistically,
      significantly greater decrease in arterial oxygen saturation, and a longer
      duration and deeper nadir of the desaturation event than did the age-matched
      control group. The desaturation index was 21 +/- 3% and 4 +/- 1% for the heart
      failure and control groups, respectively (p < 0.01).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8296741
TI  - Pulmonary valve eccentricity in d-transposition of the great arteries and
      implications for the arterial switch operation.
AB  - Neoaortic valve regurgitation is a known complication of the arterial switch
      operation for d-transposition. Its etiology and long-term effects are
      undetermined. Observations of pathologic specimens from 67 patients with d
      transposition of the great arteries with or without ventricular septal defects
      demonstrated that the pulmonary valve leaflets had unequal cusp sizes leading to
      eccentric closure. The posterior cusp was usually the largest and was
      anatomically related to the membranous ventricular septum and the anterior
      leaflet of the mitral valve. The right cusp was usually the smallest. Differences
      in cusp sizes were unrelated to age at death, sex or presence of a ventricular
      septal defect. To determine if eccentricity could be clinically detected, the
      pulmonary valves in 24 sequential patients with d-transposition were studied
      echocardiographically and angiographically. Aortic valves were studied for
      comparison. All pulmonary valves demonstrated eccentric closure in the long-axis
      echo plane, posterior in 15 patients and anterior in 9. Only 1 aortic valve
      showed eccentricity. Angiographic findings correlated with echo findings. Sixteen
      patients underwent arterial switch operations; 3 died. Twelve had angiography at
      1 year. Eleven had neoaortic valve regurgitation: 5 grade I, 4 grade II and 2
      grade III.

PMID- 8296742
TI  - Catheter ablation using radiofrequency or low-energy direct current in pediatric
      patients with the Wolff-Parkinson-White syndrome.
AB  - Percutaneous ablation of accessory pathways was performed in 22 consecutive
      children and adolescents (9 boys and 13 girls, age range 8 to 18 years). Low
      energy direct current (DC) was used exclusively in the first 6 patients, whereas
      ablation was performed with radiofrequency energy in the following 16. Accessory
      pathways were located in the left free wall in 15 patients, were posteroseptal in
      3, were in the right free wall in 3 and were anteroseptal in 1. A concealed
      accessory pathway was present in 7 patients (32%). There was no significant
      difference in clinical or electrophysiologic variables between both groups.
      Catheter ablation was successful in the initial 6 patients using low-energy DC,
      as compared with 13 of 16 patients using radiofrequency ablation. Low-energy DC
      was successful as a backup power source in all 3 patients who had unsuccessful
      radiofrequency ablation. There was no complication. The median procedural and
      fluoroscopic times for successful ablation were 2.5 hours and 49 minutes,
      respectively (p = NS between both power sources). Accessory pathway conduction
      recurred in 2 patients (33%) who had low-energy DC as compared with 1 (6%) who
      had radiofrequency ablation (p = NS). These 3 patients had successful reablation
      of their accessory pathways. In children and adolescents with accessory pathways,
      both new power sources compare favorably, with an overall success rate of
      ablation of 100% (22 of 22 patients). Radiofrequency ablation should be used
      initially because it does not require general anesthesia and is associated with a
      lower rate of recurrence of accessory pathway conduction.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8296743
TI  - Quantification of left ventricular function with an automated border detection
      system and comparison with radionuclide ventriculography.
AB  - Quantification of 2-dimensional echocardiograms with a recently developed
      automated border detection (ABD) system provides on-line estimation of left
      ventricular (LV) function. Previous studies showed that short-axis cavity area
      measurements with the ABD system approximate manually traced cavity areas
      obtained with conventional 2-dimensional echocardiography. Further clinical
      validation needs a comparison of LV function between the ABD system and
      established methods. Fractional area change and ejection fraction measured by the
      ABD system were compared with ejection fraction measured by radionuclide
      ventriculography. Echocardiographic measurements were obtained from LV short-axis
      views at the level of the papillary muscles. Calculation of ejection fraction by
      the ABD system was based on an algorithm using a modified ellipsoid model. Forty
      six patients underwent echocardiography on the same day as radionuclide
      ventriculography. Patients were included in the study if > or = 75% of the
      endocardium was visualized with conventional 2-dimensional echocardiography.
      Twenty-seven of 46 patients (59%) had a technically adequate, conventional
      echocardiogram. Fractional area change with the ABD system was highly correlated
      with ejection fraction from radionuclide ventriculography (r = 0.92; SEE 8.4%).
      Ejection fraction determined by the ABD system and radionuclide ventriculography
      also showed a strong linear relation in the 23 patients without severe wall
      motion abnormality (r = 0.90; SEE 9.5%). It is concluded that LV function
      measurements by the ABD system and radionuclide ventriculography have a strong
      linear relation.

PMID- 8296745
TI  - Usefulness of left ventricular inflow Doppler in predicting rejection in
      pediatric cardiac transplant recipients.

PMID- 8296744
TI  - Safety of single-site adenosine thallium-201 scintigraphy.
AB  - The diagnostic accuracy, safety and tolerance of adenosine thallium scintigraphy
      have been reported using a 2-site intravenous infusion with either a titrated or
      fixed-dose protocol. A single-site infusion would considerably simplify the test
      procedure, but its safety must be established before it can be recommended.
      Accordingly, 400 consecutive patients who had adenosine and thallium-201
      administered through the same intravenous line were classified into 2 groups.
      Group I (n = 201) patients received a 7-minute titrated intravenous infusion of
      adenosine, with an initial dose of 50 micrograms/kg/min that increased at 1
      minute intervals to a maximum of 140 micrograms/kg/min. Group II (n = 199)
      patients received a fixed dose of adenosine at 140 micrograms/kg/min for 6
      minutes. Adenosine significantly (p < 0.001) increased heart rate and decreased
      systolic blood pressure by similar amounts in both groups. Adverse effects
      occurred more often (88 vs 71%, p < 0.001) and started earlier (2.8 vs 3.6
      minutes, p < 0.001) in group II. There was no significant difference in the
      occurrence of second- and third-degree atrioventricular block between the 2
      groups (4.0 vs 5.0%); however, chest pain, flushing and nausea were all more
      frequent in group II. Severe side effects were seldom seen in either group and
      occurred in 9 group I and 8 group II patients. Scintigraphic findings were
      similar in both groups. Transient perfusion defects were seen more often in
      patients with than without second- or third-degree atrioventricular block (42 vs
      21%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296746
TI  - Status of the major epicardial coronary arteries at necropsy in paraplegia and
      quadriplegia.

PMID- 8296747
TI  - Efficacy of mitral balloon valvotomy in reducing the severity of associated
      tricuspid valve regurgitation.

PMID- 8296748
TI  - Safety and compatibility of betaxolol hydrochloride combined with diltiazem or
      nifedipine therapy in stable angina pectoris.
AB  - Compared with placebo, adding betaxolol 20 mg every day to nifedipine (up to 60
      mg/day in divided doses) or diltiazem (up to 360 mg/day in divided doses) for a 3
      week treatment period in 135 patients with stable angina pectoris significantly
      (p < 0.05) lengthened the time to onset of moderate angina during exercise
      tolerance tests at all treatment time points. The median increases in the time to
      onset of moderate angina at the final exercise tolerance test (end point)
      compared with baseline were 1.08 and 0.53 minutes for betaxolol and placebo
      groups, respectively (p = 0.002, betaxolol and placebo groups, respectively (p =
      0.002, betaxolol vs placebo). The time to onset of 1 mm ST-segment depression
      increased significantly (p < 0.05) with betaxolol compared with placebo at all
      but 1 treatment time point (median increase [p = 0.001] 1.77 and 0.37 minutes,
      respectively, at end point). Duration of exercise also was increased
      significantly (p < 0.05) after the third week of treatment and at end point
      (median 0.62 and 0.50 minutes, respectively; p = 0.03). Generally comparable
      results were found within the diltiazem (n = 128) and nifedipine (n = 25)
      subgroups, although the nifedipine group was too small to detect statistically
      significant differences between betaxolol and placebo treatment. Resting systolic
      blood pressure, heart rate and the rate-pressure product, measured both when
      angina occurred and at the end of exercise, also were influenced significantly (p
      < 0.05) by the betaxolol addition. The only serious adverse effect associated
      with betaxolol treatment was syncope, seen in 2 patients.

PMID- 8296749
TI  - Characteristics of conditioned and sedentary men with acute coronary syndromes.
AB  - To evaluate the role of habitual exertion in the development and manifestation of
      coronary artery disease, 36 well-conditioned men with acute coronary syndromes (4
      with unstable angina, 23 with acute myocardial infarction and 9 survivors of
      sudden ischemic death) related to sports were compared with 36 sedentary men with
      the same syndromes occurring at rest. The mean age of the study subjects was 48
      years (range 25 to 65). Patients exercised on average 6 hours/week (range 2 to
      15) for > or = 10 years (range 10 to 45). Coronary angiography was performed
      within 4 hours after the onset of symptoms. The well-conditioned men had fewer
      risk factors than the inactive men (control subjects): fewer of them smoked (58
      vs 94%, odds ratio 0.08) or had serum total cholesterol levels > or = 240 mg/dl
      (14 vs 56%, odds ratio 0.13, both p < 0.05). In addition, these men had less
      diseased (28 vs 72%, odds ratio 0.15, p < 0.02) and less severely stenotic (36 vs
      78%, odds ratio 0.16, p < 0.03) coronary arteries. The association between
      activity levels and angiographic disease severity remained significant after
      correction for risk factors. Lesion morphology, site of the lesion and presence
      of thrombus of the culprit artery and diameter and dominance of all coronary
      arteries did not differ between the well-conditioned men and control subjects.
      This study suggests that regular strenuous exercise can reduce coronary artery
      disease and shows a common pathogenesis for acute coronary syndromes related and
      unrelated to sport.

PMID- 8296750
TI  - Detection of coronary artery calcium by ultrafast computed tomography and its
      relation to clinical evidence of coronary artery disease.
AB  - Ultrafast computed tomography (CT) was used to evaluate the relation of coronary
      artery calcium, a marker of atherosclerosis, with a reported history of coronary
      artery disease (CAD) in 928 men and 290 women (mean age 53 +/- 10 years; 11% with
      previous CAD). Total calcium score was calculated as the sum of each lesion
      specific score, calculated as the product of pixel area and density > 130
      Hounsfeld units. Total score was 3 to 6 times greater (p < 0.01) and the
      probability of coronary artery calcium 30 to 40% greater (p < 0.01) in patients
      with a reported history of myocardial infarction, positive angiography, bypass
      surgery or angioplasty. From score cutoffs ranging from 1 to 500 for defining
      calcium, a negative test was accurate 93 to 98% of the time in ruling out CAD,
      whereas specificity increased from 43 to 93%; however, sensitivity decreased from
      92 to 42%. A score cutoff of 50 showed modest sensitivity (78%) and specificity
      (71%); however, the predictive value for CAD from a positive test remained low (<
      or = 40%), regardless of score cutoff. From multiple logistic regression, total
      score was also an independent indicator of CAD after considering any effects due
      to age, sex and other CAD risk factors. Further study is needed to document the
      long-term prognostic use of coronary calcium screening, including criteria that
      best project future risk of CAD.

PMID- 8296751
TI  - Does the speed of balloon deflation affect the complication rate of coronary
      angioplasty?
AB  - Two hundred consecutive coronary arteries in 157 patients undergoing angioplasty
      were randomized to fast or slow balloon deflation. Angioplasty was successful in
      188 cases (101 with slow and 87 with fast deflation). There was no significant
      difference between the 2 groups with regard to the total number of dissections,
      although there was a greater number in the slow deflation group, and no
      difference in the number of minor dissections (National Heart, Lung, and Blood
      Institute types A and B). There was a significantly greater number of more severe
      dissections (types C to F) in the slow deflation group (20 vs 5; p = 0.013). It
      is proposed that the greater number of severe dissections is due to either
      increased turbulence or movement of the partially deflated balloon during slow
      deflation. Thus, slow balloon deflation during coronary angioplasty is associated
      with a higher complication rate than is conventional rapid deflation.

PMID- 8296752
TI  - Time to reperfusion with direct coronary angioplasty and thrombolytic therapy in
      acute myocardial infarction.
AB  - An analysis was performed of the Mayo Clinic randomized trial of direct
      percutaneous transluminal coronary angioplasty and tissue-type plasminogen
      activator (t-PA) to determine the time required to achieve reperfusion with
      direct coronary angioplasty. Because patients in the Mayo trial assigned to t-PA
      did not undergo protocol coronary angiography, reperfusion rates from the
      Thrombolysis in Myocardial Infarction (TIMI) I trial in which patients underwent
      coronary angiography 30, 60 and 90 minutes after thrombolytic therapy were used
      for comparison. TIMI perfusion grade 2 or 3 flow in the infarct artery was
      considered to represent reperfusion after thrombolysis. In the 56 patients
      assigned to t-PA, the mean time from randomization to initiation of the t-PA
      infusion was 20 minutes. Twenty minutes were therefore added to the previously
      reported 30-, 60- and 90-minute reperfusion rates to express these in terms of
      time from randomization (50, 80 and 110 minutes). In the 48 patients who had
      direct angioplasty, the mean time from randomization to arrival in the cardiac
      catheterization laboratory was 45 minutes; it took a mean of 6 additional minutes
      for patients to be prepared and draped and arterial access obtained, and a mean
      of 27 additional minutes to complete angiography and achieve reperfusion. At 50,
      80 and 110 minutes after randomization, the reperfusion rates for direct coronary
      angioplasty were 12, 54 and 83%, similar to previously reported TIMI reperfusion
      rates with t-PA (24, 57 and 71%, respectively, p = NS) but significantly greater
      at 80 and 110 minutes than was reported for streptokinase (8, 23 and 31%,
      respectively, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296753
TI  - Clinical predictors of implantable cardioverter-defibrillator shocks (results of
      the CASCADE trial). Cardiac Arrest in Seattle, Conventional versus Amiodarone
      Drug Evaluation.
AB  - The Cardiac Arrest in Seattle, Conventional Versus Amiodarone Drug Evaluation
      (CASCADE) study evaluated antiarrhythmic drug therapy in high-risk survivors of
      out-of-hospital ventricular fibrillation. Antiarrhythmic drug therapy for 228
      patients was randomized to amiodarone or conventional antiarrhythmic drugs.
      Additional therapy with an implantable cardioverter-defibrillator was provided to
      105 of these patients. Clinical predictors of shocks were evaluated for the 88
      patients with coronary artery disease (amiodarone 46, conventional 42), treated
      with an implantable cardioverter-defibrillator. Survival free of all shocks at 2
      years was 77% for patients taking amiodarone and 42% for those receiving
      conventional therapy (p = 0.014). Two-year survival free of syncopal shocks was
      98% for amiodarone-treated patients and 81% for those receiving conventional
      agents (p = 0.01). Multiple clinical factors were evaluated by Cox analysis for
      potential clinical predictors of shocks. The independent clinical predictors of
      shocks were low ejection fraction (p = 0.002), female gender (p = 0.007) and
      conventional antiarrhythmic drug therapy (p = 0.015). The only independent
      predictor of a shock associated with syncope was conventional antiarrhythmic drug
      therapy (p = 0.035). Patients treated with amiodarone receive fewer shocks than
      patients treated with conventional drug therapy.

PMID- 8296754
TI  - Asymmetric left ventricular remodeling due to isolated septal thickening in
      patients with systemic hypertension and normal left ventricular masses.
AB  - Early identification of left ventricular (LV) structural changes may have an
      impact on the outlook of patients with essential hypertension. Of 669 untreated
      hypertensive subjects, 496 (74%) with normal LV mass at echocardiography (< 125
      g/m2) were grouped according to normal LV geometry (n = 303; 61%), asymmetric LV
      remodeling due to isolated septal thickening (n = 111; 22%), asymmetric LV
      remodeling due to isolated posterior wall thickening (n = 5; 1%), or concentric
      LV remodeling due to septal and posterior wall thickening (n = 77; 16%).
      Remodeling was defined as twice the thickness of septum or posterior wall divided
      by the internal diameter at end diastole > 0.45. Twenty-four-hour noninvasive
      ambulatory blood pressure (BP) monitoring was performed in all subjects. Compared
      with subjects with normal LV geometry, those with asymmetric LV remodeling due to
      isolated septal thickening showed increased clinic BP (158/100 vs 153/97 mm Hg,
      both p < 0.05), mean daytime ambulatory BP (144/95 vs 138/90 mm Hg, both p <
      0.01), mean nighttime ambulatory BP (128/80 vs 122/76 mm Hg, both p < 0.01), LV
      mass (99 vs 89 g/m2, p < 0.001), total peripheral resistance (1,881 vs 1,562
      dynes s cm-5, p < 0.01) and known duration of hypertension (5.5 vs 3.6 years, p <
      0.01) and decreased stroke index (39 vs 47 ml/m2, p < 0.01).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8296755
TI  - Baroreflex function during 45-degree passive head-up tilt before and after long
      term thiazide therapy in the elderly with systolic systemic hypertension.
AB  - The ratio of the 30th to the 15th cardiac cycle duration on an electrocardiogram
      (30:15 ratio) immediately after active standing from the supine position has been
      used as one of the markers of baroreflex function. A ratio of < or = 1.0 has been
      suggested to indicate baroreflex dysfunction. Blood pressure (BP) changes were
      measured and the 30:15 ratio was calculated after standing and during 45-degree
      passive head-up tilt from the supine position in 10 nondiabetic men (mean age +/-
      SE 70.1 +/- 1.05 years, and BP < 150/90 mm Hg). After tilt the decrease in
      systolic BP (from 132 +/- 4.8 to 117 +/- 6.3 mm Hg; p < 0.001) appeared to be
      larger than that after standing (from 132 +/- 4.6 to 123 +/- 5.8 mm Hg; p <
      0.01), whereas the 30:15 ratios were 0.965 +/- 0.006 and 0.970 +/- 0.014,
      respectively, which suggested baroreflex dysfunction. Although the mean of the 2
      ratios did not differ, the variance appeared to be less during tilting than after
      standing. Thus, the 45-degree passive head-up tilt appeared to be a better and
      more uniform inducer of orthostatic stress than active standing. Therefore, 45
      degree head-up tilt was used in a group of 10 nondiabetic male patients (aged 70
      +/- 1.46 years) with isolated systolic hypertension (systolic BP > 160 mm Hg,
      diastolic BP of < 90 mm Hg) to assess their baroreflex function. Upon tilting,
      their systolic BP decreased from 190 +/- 5.5 to 179 +/- 5.8 mm Hg (p < 0.05) and
      their 30:15 ratio was 0.985 +/- 0.011.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296756
TI  - Abnormalities of pulmonary function in patients with congestive heart failure,
      and reversal with ipratropium bromide.
AB  - Patients with congestive heart failure (CHF) have baseline restrictive and
      obstructive abnormalities in pulmonary function. Thus, improvement of respiratory
      parameters may provide a new method for the treatment of CHF. Ipratropium is an
      inhaled anticholinergic bronchodilator with no reported cardiac or systemic
      effect. A pilot study was performed to investigate the acute effects of a 72
      micrograms inhaled dose of ipratropium bromide on pulmonary function and
      pulmonary artery pressures in 18 nonsmokers and 11 smokers with severe (New York
      Heart Association class 2 or 3), stable CHF who were referred for orthotopic
      cardiac transplantation. An unmatched group of 10 healthy subjects (5 men and 5
      women, mean age 36.8 +/- 1.8 years) were studied with pulmonary function testing
      alone. Forced expiratory volume in 1 second (FEV1) in 15 of 18 nonsmokers with
      CHF showed a favorable response with a mean improvement of 5.1% (2.74 +/- 0.20 to
      2.89 +/- 0.19 liter after drug treatment; p = 0.0026). Forced expiratory flow
      between 25 and 75% of the forced vital capacity (FEF25-75) improved by 19% (2.50
      +/- 0.25 to 3.09 +/- 0.28 liter/s; p = 0.0013). Eight of 11 smokers with CHF
      responded with a 9.5% increase in FEV1 (2.32 +/- 0.21 to 2.54 +/- 0.19 liter; p =
      0.0006) and a 23.2% increase in FEF25-75 (1.82 +/- 0.38 to 2.37 +/- 0.46 liter/s;
      p = 0.0029). Pulmonary artery pressures, cardiac output, systemic arterial
      pressures, and cardiac rate and rhythm were unaffected by administration of the
      drug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296757
TI  - Clinical and health care cost consequences of infective endocarditis in mitral
      valve prolapse.
AB  - Although mitral valve prolapse (MVP) predisposes to infective endocarditis (IE),
      both the clinical consequences of IE and the increment in health care costs it
      imposes on patients with MVP remain uncertain. Accordingly, 21 MVP patients with
      IE and 41 age- and sex-matched control subjects with initially uncomplicated MVP
      were followed (95% complete) a mean of 8 years. Outcomes included death,
      complications, health care use and cumulative incremental costs. More MVP
      patients with IE died (25 vs 5%, p < 0.05), underwent valve surgery (40 vs 8%, p
      < 0.01), had heart failure (50 vs 5%, p < 0.01) or embolization (53 vs 11%, p <
      0.01), underwent cardiac catheterization (40 vs 13%), and saw their physicians >
      2 times per year (88 vs 33%). The cumulative incremental cost of IE (1990
      dollars) was $46,132 per case. Thus, IE in patients with MVP causes considerable
      cumulative morbidity and incremental health care costs.

PMID- 8296758
TI  - Color-coded Doppler imaging of the vena contracta as a basis for quantification
      of pure mitral regurgitation.
AB  - The narrowest central flow region of a jet is defined as the vena contracta. This
      term is applied also to the contracted zone of the Doppler color flow image of a
      jet at its passage through an incompetent mitral valve. The clinical
      applicability of measuring the size of the vena contracta by transthoracic color
      coded Doppler echocardiography for estimating the severity of mitral
      regurgitation (MR) was evaluated. In 78 of 82 patients with angiographically
      proved MR, a coherent flow image across the valve was visualized. The maximal
      diameter in the apical long-axis view was considered as a representative value
      for the size of the vena contracta. In comparison with the maximal left atrial
      velocity pixel area, this parameter revealed higher correlations to the
      angiographic degree of MR and to the regurgitant volume (r = 0.94 vs 0.72, and
      0.83 vs 0.71, respectively). The highest positive and negative predictive
      accuracies for differentiating mild-to-moderate from severe MR were determined
      for a diameter of 6.5 mm (88 and 96%, respectively). Because the vena contracta
      is directly related to the severity of MR, it is concluded that it is helpful to
      use this parameter instead of the maximal velocity pixel area for
      semiquantitative grading.

PMID- 8296759
TI  - Usefulness of mean aortic valve gradient and left ventricular diastolic filling
      pattern for distinguishing symptomatic from asymptomatic patients.
AB  - Consecutive, symptomatic (n = 15) and asymptomatic (n = 25) men with aortic
      stenosis (valve area < 1.2 cm2) and no clinical evidence of myocardial ischemia
      underwent radionuclide angiography at rest and during supine bicycle ergometry.
      Ejection fraction, diastolic filling pattern and aortic valve area/gradient were
      measured on enrollment and when patients became symptomatic (n = 10) or underwent
      valve replacement (n = 22) during a 2-year follow-up period. Both groups had
      similar heart rate, blood pressure and ejection fractions, but mean aortic
      gradients were higher in symptomatic (53 +/- 4 mm Hg) than asymptomatic (37 +/- 2
      mm Hg) subjects p < 0.01. Functional limitation evoked by exercise was prevalent
      even in the asymptomatic group but symptomatic patients exercised to lower work
      levels than asymptomatic subjects (184 +/- 27 and 307 +/- 32 kg.m/min,
      respectively, p = 0.02). Ejection fraction failed to increase with exercise in
      either group. Symptomatic subjects had supranormalization of early diastolic
      filling with shorter time to the peak filling rate than asymptomatic subjects
      (137 +/- 16 and 172 +/- 9 ms, respectively, p < 0.05) and a greater first 1/3
      filling fraction. The 10 patients who became symptomatic during follow-up had
      higher first 1/3 filling fractions (53 +/- 7 and 42 +/- 5%, respectively) and
      mean gradients (41 +/- 4 and 33 +/- 2 mm Hg, respectively) than subjects who
      remained asymptomatic, p < 0.05. High mean aortic gradients, impaired exercise
      tolerance and enhanced early diastolic filling distinguish symptomatic from
      asymptomatic patients.

PMID- 8296760
TI  - Left ventricular diastolic dysfunction in lymphocytic myocarditis as assessed by
      Doppler echocardiography.
AB  - Pulsed-wave Doppler echocardiography of left ventricular (LV) inflows was
      performed in 30 consecutive patients with biopsy-proven lymphocytic myocarditis.
      There were 21 men and 9 women (mean age 50 +/- 15 years). LV ejection fraction
      was < or = 30% in 73% of the patients. Sixty-six percent were in New York Heart
      Association functional class III to IV. Peak early (E) velocity, late (A)
      velocity, deceleration time and filling pattern were assessed. These values were
      compared with a control population. E velocity in lymphocytic myocarditis was
      significantly higher than in control subjects (79 +/- 34 vs 67 +/- 14 cm/s, p =
      0.0034). A velocity was lower in patients with myocarditis than in control
      subjects (38 +/- 20 vs 49 +/- 12 cm/s, p = 0.0001). Correspondingly, the E/A
      ratio was greater in the myocarditis group (2.5 +/- 1.3 vs 1.5 +/- 0.5, p <
      0.0001). In particular, mean deceleration time in patients with myocarditis was
      significantly lower than that of control subjects (151 +/- 52 vs 194 +/- 30 ms, p
      < 0.0001). Diastolic filling patterns were abnormal in 29 of 30 patients (97%)
      with lymphocytic myocarditis, revealing a restrictive pattern in 25, abnormal
      relaxation in 4 and a normal pattern in 1. Lymphocytic myo-carditis is therefore
      associated with LV diastolic dysfunction of a predominantly restrictive pattern.

PMID- 8296761
TI  - Atrial septal defect occlusion with the buttoned device (a multi-institutional
      U.S. trial).
AB  - A clinical trial was conducted of the buttoned device for transcatheter closure
      of ostium secundum atrial septal defect. Occlusion was attempted in 57 patients
      aged 1 to 62 years (median 5). The procedure was abandoned in 7 patients after 1
      or more unsuccessful attempts, and devices were released in 50 patients. Urgent
      surgical retrieval was necessary in 4 patients because of unstable device
      position: 3 devices "unbuttoned," with migration of the counteroccluder to the
      pulmonary artery or inferior vena cava, and 1 intact device embolized to the main
      pulmonary artery. All patients remained stable and underwent successful
      operation. Successful device implantation was therefore achieved in 46 patients,
      with immediate reduction in Qp/Qs from 1.8 +/- 0.6 to 1.1 +/- 0.2 (mean +/- SD, p
      < 0.0001). At most recent follow-up (1 to 20 months), 45 of 46 patients (98%)
      have no shunt or a trivial residual shunt. The prevalence of residual shunts
      declined from 65% at 1 month to 19% at 12 months after the occlusion procedure (p
      < 0.0001). Complications included unbuttoning of a fourth device, transient
      tricuspid regurgitation in 2 patients, and transient mitral regurgitation in 2
      patients. An episode of asymptomatic atrial flutter was noted in a 46-year-old
      patient which may have been related to device implantation, but which has not
      recurred. There have been no cases of endocarditis or thromboembolism in 350
      patient-months of follow-up. The buttoned device provided effective closure of
      the atrial septal defect in 45 of 57 patients (79%) in whom implantation was
      attempted and in 45 of 46 patients (98%) in whom device implantation was
      successfully accomplished.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296762
TI  - Systolic and diastolic function in tricuspid valve atresia before the Fontan
      operation.
AB  - Systolic and diastolic function were assessed at preoperative cardiac
      catheterization in 6 patients with classic tricuspid atresia and were compared
      with those in control subjects. All patients had systemic-to-pulmonary shunts.
      Left ventricular end-systolic and end-diastolic volumes and masses were
      significantly larger in the patient group; stroke volume and the ratio of volume
      to mass were also higher, but not significantly. Mean end-diastolic, peak
      systolic and end-systolic pressures were similar. Mean stress at end-systole and
      peak systole were significantly higher in the patient group. Operant chamber
      stiffness tended to be lower than normal, but was not statistically significant,
      and myocardial stiffness was normal for the patient group also. Indexes of
      systolic function were compared. The rate-corrected mean velocity of fiber
      shortening in the patient group was lower and its relation with stress at end
      systole was variable with 4 abnormal patients. The ratio of stress at end
      systole/end-systolic volume was significantly lower in patients. The duration of
      hospital stay did not correlate with end-diastolic volume or any parameter. Thus,
      this study found abnormalities of load-dependent and independent indexes of
      systolic function with normal diastolic function in young preoperative patients
      with tricuspid atresia.

PMID- 8296763
TI  - Value of the 12-lead electrocardiogram at hospital admission in the diagnosis of
      pulmonary embolism.
AB  - In 49 consecutive patients (27 men and 22 women, age range 44 to 86 years)
      presenting with acute symptoms and with subsequently proven pulmonary embolism,
      and without previous lung disease, the 12-lead electrocardiograms obtained at
      hospital admission were reviewed in a blinded fashion to identify
      electrocardiographic features suggestive of right ventricular overload. Pulmonary
      embolism was considered probable in 37 patients (76%), from the presence of > or
      = 3 of the following abnormalities: (1) incomplete or complete right bundle
      branch block (n = 33); which was associated with ST-segment elevation (n = 17)
      and positive T wave (n = 3) in lead V1; (2) S waves in leads I and aVL of > 1.5
      mm (n = 36); (3) a shift in the transition zone in the precordial leads to V5 (n
      = 25); (4) Q waves in leads III and aVF, but not in lead II (n = 24); (5) right
      axis deviation, with a frontal QRS axis of > 90 degrees (n = 16), or an
      indeterminate axis (n = 15); (6) a low-voltage QRS complex of < 5 mm in the limb
      leads (n = 10); and (7) T-wave inversion in leads III and aVF (n = 16) or leads
      V1 to V4 (n = 13), which occurred more often in patients with symptoms for > 7
      days. In the 12 patients with normal electrocardiograms at admission, serial
      electrocardiograms revealed diagnostic features of embolism in an additional 3
      patients. Two-dimensional Doppler echocardiography at admission revealed
      tricuspid valve regurgitation and an increased right ventricular end-diastolic
      diameter in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296764
TI  - Maximal exercise tolerance as a therapeutic end point in heart failure--are we
      relying on the right measure?

PMID- 8296765
TI  - Skeletal muscle strength and endurance in chronic congestive heart failure
      secondary to idiopathic dilated cardiomyopathy.

PMID- 8296766
TI  - Critical pulmonary valve stenosis in the neonate: a technique to facilitate
      balloon dilation.

PMID- 8296767
TI  - Cardiac responses assessed by echocardiography to changes in preload in
      hypertrophic cardiomyopathy.

PMID- 8296768
TI  - Vegetables, fruit, and colon cancer in the Iowa Women's Health Study.
AB  - Previous epidemiologic studies have shown an inverse association between
      vegetable and fruit consumption and colon cancer risk; few of these studies have
      been prospective or have focused on women. This report describes results from a
      prospective cohort study of 41,837 women aged 55-69 years who completed a 127
      item food frequency questionnaire in 1986 and were monitored for cancer incidence
      for 5 years via the State Health Registry of Iowa. After specific exclusion
      criteria were applied, 212 colon cancer cases and 167,447 person-years were
      available for analysis. Intakes of 15 vegetable and fruit groups and dietary
      fiber were the major factors of interest. Consumption of garlic was inversely
      associated with risk, with an age- and energy-adjusted relative risk of 0.68 (95%
      confidence interval (CI) 0.46-1.02) for the uppermost versus the lowermost
      consumption levels. Inverse associations were also observed for intakes of all
      vegetables and dietary fiber; age- and energy-adjusted relative risks for the
      uppermost versus the lowermost intake quartiles were 0.73 (95% CI 0.47-1.13) and
      0.80 (95% CI 0.49-1.31), respectively. Associations for the other vegetable and
      fruit groups were less remarkable.

PMID- 8296769
TI  - Re: "Arsenic ingestion and internal cancers: a review".

PMID- 8296770
TI  - Re: "P values, hypothesis tests, and likelihood: implications for epidemiology of
      a neglected historical debate".

PMID- 8296771
TI  - Calcium, vitamin D, dairy foods, and the occurrence of colorectal adenomas among
      men and women in two prospective studies.
AB  - A high intake of calcium, vitamin D, or specific dairy products is thought to
      reduce the incidence of colorectal cancer. The association of these nutrients and
      foods with the occurrence of colorectal adenomas, precursors of cancer, was
      studied in two large US cohort studies. Cases were patients with a diagnosis of
      adenomatous polyps of the left colon or rectum (331 men, 1986-1990; 350 women,
      1980-1988), and controls were persons with endoscopic findings negative for
      adenoma (9,159 men and 8,585 women). After adjustment for age, total energy,
      family history of colorectal cancer, body mass index, alcohol consumption,
      folate, intake of saturated fat and fiber, indications for endoscopy, and
      previous endoscopy, total calcium intake was not associated with the risk for
      adenoma (relative risk (RR), highest vs. lowest quintile of intake: men, 1.13,
      95% confidence interval (CI) 0.76-1.66; women, 1.17, 95% CI 0.81-1.69). Total
      vitamin D intake was unrelated to the risk for adenoma in men (RR = 1.29, 95% CI
      0.87-1.93). An inverse nonsignificant association was observed in women in the
      1980-1988 analyses (RR = 0.68, 95% CI 0.41-1.13, trend p = 0.09), mainly
      attributable to the intake of multivitamin supplements, but an analysis of 4-year
      data (1984-1988) using a more detailed dietary assessment showed no association
      with vitamin D (RR = 1.04, 95% CI 0.65-1.67). Milk consumption and intake of
      total fermented dairy products were not related to adenoma risk. In conclusion,
      the occurrence of colorectal adenoma was neither related to calcium intake nor to
      milk consumption, whereas vitamin D from supplements but not diet was slightly,
      but not significantly, inversely associated with risk among women only.

PMID- 8296772
TI  - Occupational exposures associated with male breast cancer.
AB  - The role of occupational exposure to heat and electromagnetic fields was
      investigated in a case-control study of male breast cancer. Seventy-one cases
      reported to the New York State Tumor Registry between 1979 and 1988 were compared
      with 256 healthy male controls. Controls were frequency matched to cases by race,
      year of diagnosis, and age in 5-year intervals. Unconditional logistic regression
      modeling indicated that males with occupations that involved heat exposure had an
      elevated risk for the disease. The age- and county-adjusted odds ratio was 2.3
      (95% confidence interval (CI) 0.95-5.3). Exposure to heat on the job could
      influence testicular function. No increase in disease risk was observed for males
      believed to have occupational exposure to electromagnetic fields (odds ratio =
      0.7, 95% CI 0.3-1.9).

PMID- 8296773
TI  - Epidemiology of traumatic spinal cord injury and acute hospitalization and
      rehabilitation charges for spinal cord injuries in Oklahoma, 1988-1990.
AB  - Few injuries result in more profound and long-term disability than traumatic
      spinal cord injury. This study describes the demographic and epidemiologic
      characteristics of traumatic spinal cord injury among Oklahoma residents reported
      to the statewide, population-based surveillance system in 1988-1990; initial
      acute hospital and rehabilitation charges for 1989 are also included. There was a
      reported incidence rate of 40 per million population. Based on a reporting
      sensitivity of 77%, the "true" incidence of spinal cord injury was estimated to
      be 51 per million population. Motor vehicle crashes accounted for 48% of
      injuries. Males aged 15-29 years and blacks were at highest risk of injury. Among
      blacks, the injury rate due to violence was seven times that for whites or Native
      Americans. Alcohol/drug use was a contributing factor in 39% of injuries and was
      highest among males aged 20-29 years (58%), Native Americans (57%), and victims
      of motor vehicle crashes (48%) or violence (51%). The combined initial charges
      for persons receiving both acute and rehabilitative care ranged from $9,790 to
      $666,510, with a median of $53,410 per patient; for complete quadriplegia, the
      combined median charge was $88,585. Despite its low incidence, hospitalization
      and rehabilitation charges for spinal cord injury in 1989 caused an economic
      burden of an estimated $8.4 million. While the charges presented were only a
      small portion of the total costs of spinal cord injury, they further substantiate
      the need for prevention efforts targeting these debilitating, often permanent
      injuries. These efforts should target young males and blacks, and should focus on
      preventing injuries associated with motor vehicle crashes, violence, and
      alcohol/drug use.

PMID- 8296774
TI  - Components of drinking water and risk of cognitive impairment in the elderly.
AB  - The relation between aluminum, fluorine, calcium, and pH in drinking water and
      the risk for cognitive impairment was studied using data collected in 1988-1989
      in a population-based survey of 3,777 French men and women aged 65 years and
      older (the Paquid study). Cognitive impairment was defined as a score lower than
      24 on the Mini-Mental State Examination. Data related to drinking water came from
      two prospective measurement surveys whose reliability was checked by a
      variability study. A mixed effects logistic regression was performed, adjusting
      for the effects of the age, sex, educational level, and occupation of the
      participants. A significant protective effect was found for high calcium
      concentration (odds ratio = 0.8 for a concentration > or = 75 mg vs. < 75 mg, p =
      0.015). For aluminum, no significant effect was found when pH was not included in
      the model, but the results showed a weak interaction between aluminum and pH.
      When the four variables (calcium, aluminum, pH, and aluminum x pH interaction)
      were considered in the statistical analysis as a group, this group was
      significantly related to cognitive impairment (p = 0.01).

PMID- 8296775
TI  - Depressive symptomatology in women and residential proximity to high-voltage
      transmission lines.
AB  - A number of epidemiologic studies indicate an association between depression and
      proximity to high-voltage transmission lines. These studies have been criticized,
      however, for using surrogate measures of electromagnetic fields and
      unstandardized measures of depression. In an effort to overcome these
      limitations, the authors administered the Center for Epidemiological Studies
      Depression scale (CES-D) in 1992 to 152 women in Orange County, California, who
      lived either adjacent to a transmission line or one block away. The results
      indicated that the average magnetic field level is 4.86 mG at the front door of
      homes adjacent to transmission lines and 0.68 mG at the front door of homes one
      block away. There was no significant difference in CES-D scores between the
      groups when demographic variables were controlled for. The homogeneity of the
      study population may limit the generalizability of findings.

PMID- 8296776
TI  - Age at natural menopause and sociodemographic status in Finland.
AB  - Differences in age at natural menopause by occupation, education, and place of
      residence were examined using a cross-sectional population sample of Finnish
      women aged 45-64 years (n = 1,713, response rate 86%). The sample was selected at
      random from the Finnish Population Register in 1989 (final n = 1,505, 75%).
      Kaplan-Meier estimates showed the median age at natural menopause to be 51 years
      for all women (95% confidence interval (CI) 50.6-51.4). The median menopausal age
      of smokers and nulliparous women was 50 years; that of nonsmokers and women whose
      first full-term pregnancy occurred before the age of 25 years was 52 years.
      Differences between occupational and educational groups were statistically
      significant (Mantel-Cox test for occupation, p < 0.02; for education, p < 0.03).
      In the Cox proportional hazards model, the odds ratio of the occurrence of
      natural menopause among upper white-collar women was 0.74 (95% CI 0.57-0.96) and
      among the most educated women (education > 11 years) it was 0.75 (95% CI 0.59
      0.96), adjusted to reflect smoking, use of hormones, body mass index, and age at
      first full-term pregnancy. Sociodemographic variables appear to be associated
      with age at natural menopause in a representative sample of Finnish women.

PMID- 8296777
TI  - Outbreaks in highly vaccinated populations: implications for studies of vaccine
      performance.
AB  - Most of the factors associated with the failure of a vaccination to provide
      protective immunity are not distributed uniformly or randomly within populations.
      This paper explores the extent to which a nonrandom distribution of vaccination
      failures and the selection of exceptional situations for investigation may
      influence estimates of vaccine performance. The authors show that outbreak
      investigations will tend to underestimate vaccination efficacy, and that the
      extent of underestimation will be related directly to the size of the epidemic
      triggering an investigation, the vaccination coverage in the community, and the
      extent of clustering of vaccination failures in the population; it will be
      related inversely to the size of and contact intensity within the investigated
      community. These potential sources of bias are not the only problems that arise
      in estimating vaccine efficacy, but they should be taken into consideration when
      analyzing and interpreting outbreak situations. The fact that outbreak
      investigations carried out within the United States during the past decade have
      provided estimates of measles vaccination efficacy on the order of 95% is
      consistent with a somewhat higher overall "true" efficacy of current vaccines and
      procedures in the total population. It is important to understand better the
      frequency, distribution, and risk factors for vaccination failures in
      populations.

PMID- 8296778
TI  - Assessing intervention effects in the Minnesota Heart Health Program.
AB  - The Minnesota Heart Health Program is a 13-year research and demonstration
      project to reduce morbidity and mortality from coronary heart disease in whole
      communities in the upper Midwest. Six communities were selected for the study:
      three intervention and three comparison sites, matched to increase baseline
      comparability. After 2-4 years of baseline observations, a 5- to 6-year program
      of intensive intervention was introduced in the three intervention communities.
      Periodic cross-sectional and cohort surveys provided data on risk factors and
      related behaviors. Regression adjustments within and between communities reduced
      the confounding influences of important covariates and the variance inflation
      associated with the nesting of individuals within communities and surveys. Post
      hoc stratification allowed exploration of the main and strata-specific effects of
      the intervention program. Finally, the intervention effect was modeled as a
      departure from the trend line fit to the nonintervention city-year means.
      Together, these procedures explicitly acknowledged the component of variance
      associated with communities, and so avoided a major source of bias created in the
      usual analysis when that variation is ignored. They also increased the
      interpretability of the analyses and reduced the mean square errors used to
      assess the treatment effects.

PMID- 8296779
TI  - Obesity as a risk factor for osteoarthritis of the hand and wrist: a prospective
      study.
AB  - The Tecumseh Community Health Study provides an opportunity to investigate the
      role of obesity in the etiology of osteoarthritis. This longitudinal study,
      conducted in Tecumseh, Michigan, began in 1962 with baseline examinations of
      clinical, biochemical, and radiologic characteristics. A 1985 reexamination of
      the cohort characterized osteoarthritis status in 1,276 participants, 588 males
      and 688 females, who were aged 50-74 years at this follow-up. Baseline obesity,
      as measured by an index of relative weight, was found to be significantly
      associated with the 23-year incidence of osteoarthritis of the hands among
      subjects disease free at baseline. Greater baseline relative weight was also
      associated with greater subsequent severity of osteoarthritis of the hands. The
      difference between baseline and follow-up weight values was not significantly
      associated with the incidence of osteoarthritis of the hands. Furthermore, there
      was no evidence that development of osteoarthritis subsequently led to increased
      incidence of obesity.

PMID- 8296780
TI  - Dietary cation intake and blood pressure in black girls and white girls.
AB  - The authors examined the relative importance of dietary sodium, potassium,
      calcium, and magnesium intakes as correlates of blood pressure in a cross
      sectional analysis of 987 black and 1,043 white 9- and 10-year-old girls from
      Richmond, California, Cincinnati, Ohio, and Washington, DC, who were enrolled in
      the National Heart, Lung, and Blood Institute Growth and Health Study between
      January 1987 and May 1988. Dietary intake was measured using a 3-day food record.
      Dietary cation intake was not associated with blood pressure in black girls. An
      inverse association between magnesium intake and diastolic (fifth Korotkoff
      phase) blood pressure was found in white girls (p < 0.01). After controlling for
      factors often associated with blood pressure, such as pulse rate, body mass
      index, and household income, the authors found that dietary magnesium intake
      (range, 53-511 mg/day) continued to be associated with diastolic (fifth Korotkoff
      phase) blood pressure in white girls, such that each 100-mg/day increase in
      intake was associated with a 3.22-mmHg decrease in diastolic pressure (95%
      confidence interval -5.70 to -0.75). However, after adjustment for dietary fiber
      intake, the authors were no longer able to discern an association between dietary
      magnesium intake and blood pressure. They conclude that the body mass index and
      pulse rate are the strongest correlates of blood pressure in 9- and 10-year-old
      black girls and white girls and that studies examining the relation between
      dietary magnesium and blood pressure should control for the effects of dietary
      fiber intake.

PMID- 8296781
TI  - Secular trends in blood pressure among adult blacks and whites aged 18-34 years
      in two body mass index strata, United States, 1960-1980.
AB  - Secular trends in blood pressure among young adults reflect the proportion of the
      population at risk of developing hypertension and may be markers of progress in
      primary prevention. National health examination data from three successive
      surveys were analyzed to assess blood pressure trends for adult blacks and whites
      aged 18-34 years in two body mass index (BMI; weight (kg)/height (m)2) strata (<
      25 or > or = 25). Blood pressure was categorized into a four-point ordinal scale
      using the weighted, within-sex 50th, 75th, and 90th percentiles for 18- to 24
      year-old adults in the 1960-1962 survey. The effects were analyzed with
      cumulative logit models with alpha = 0.01. The systolic blood pressure decreased
      moderately for 25- to 34-year-old males and for females except those aged 25-34
      years with a BMI of > or = 25. Diastolic blood pressure increased among males
      with a BMI of > or = 25 and among white males with a BMI of < 25, but did not
      show a significant overall trend among females. A BMI of > or = 25 was associated
      with substantially higher blood pressure in each survey, except for one age-sex
      race subgroup. Racial differences within BMI were less consistent than the
      differences across BMI strata. In summary, the situation with respect to
      hypertension among females may have improved during this time period but for
      males may have worsened with respect to diastolic blood pressure. Data for both
      sexes support a need for population-wide obesity prevention to reduce the
      incidence of hypertension.

PMID- 8296782
TI  - Changes in serum cholesterol level and mortality: a 30-year follow-up. The
      Finnish cohorts of the seven countries study.
AB  - The association of past changes in serum cholesterol level with cause-specific
      mortality between 1974 and 1989 was examined in a cohort of 784 Finnish men aged
      55-74 years who were free of symptomatic coronary heart disease in 1974. Changes
      in serum cholesterol level were computed based on measurements made in 1959,
      1964, 1969, and 1974. Of the 405 deaths, 202 were due to cardiovascular diseases
      and 107 due to cancer. Men with a decline in serum cholesterol level between 1959
      and 1974 also experienced greater than average declines in body mass index and
      tended to be more often current smokers in 1974. Among 339 men aged 65-74 years
      in 1974, men in the lowest tertile of serum cholesterol change, i.e., with
      greatest declines, had increased cardiovascular (hazard ratio, 1.58; 95%
      confidence interval 1.00-2.50) and all-cause (hazard ratio, 1.46; 95% confidence
      interval 1.06-2.02) mortality compared with men in the middle tertile of change,
      i.e., with least change, in multivariate analysis. Among 445 men aged 55-64 years
      in 1974, there was a significant U-shaped association between change in serum
      cholesterol level and coronary and all-cause mortality risk. The authors suggest
      that both the decline in serum cholesterol level and the associated high
      mortality may be caused by a third factor, such as increased prevalence of
      chronic diseases or other changes associated with aging. This would help to
      explain why several studies have not found an association of serum cholesterol
      with coronary risk among the elderly.

PMID- 8296783
TI  - Predictors of mortality from idiopathic dilated cardiomyopathy in 356,222 men
      screened for the Multiple Risk Factor Intervention Trial.
AB  - Possible predictors of mortality from idiopathic dilated cardiomyopathy were
      studied in 356,222 men who were screened as part of the Multiple Risk Factor
      Intervention Trial. The vital status of each member of this cohort was
      ascertained through 1986. Death certificates were obtained from state health
      departments and coded by a trained nosologist. Individuals with a history of
      myocardial infarction were excluded. A total of 206 deaths due to idiopathic
      dilated cardiomyopathy occurred in the cohort of 356,222 men after an average of
      12 years of follow-up. The age-specific rates of mortality from idiopathic
      dilated cardiomyopathy increased from 0.10 per 10,000 person-years among men aged
      35-39 years to 1.16 per 10,000 person-years among men aged 55-57 years. The
      proportional hazards model was used to obtain adjusted estimates of relative
      risks. Statistically significant, independent associations were observed with
      cigarettes smoked per day (p < 0.001), diastolic blood pressure (p < 0.001), and
      diabetes mellitus (relative risk (RR) = 2.97, p < 0.001). Black race was also
      associated with an increased risk of death from idiopathic dilated cardiomyopathy
      (RR = 1.59 and p = 0.045 without adjustment for income; RR = 1.58 and p = 0.058
      with adjustment for income). No association was found with serum cholesterol or
      income. The information about possible risk factors obtained in this study may
      contribute to future preventive programs for idiopathic dilated cardiomyopathy.

PMID- 8296784
TI  - Perinatal, infant, and child death rates among the Old Order Amish.
AB  - The Old Order Amish are a distinct ethnic group with a very high birth rate and
      patterns of perinatal risk factors quite different from those of the general
      population. This study reports marital fertility and perinatal, infant, and child
      death rates for an entire Amish settlement of approximately 10,000 individuals,
      centered around Geauga County, Ohio. All 6,623 births from 1948 to 1988 listed in
      a directory of Geauga Settlement Amish households were studied. The childbearing
      experience of all 475 married women over the age of 44 years was also described.
      Women aged > 44 years had a median of 8.3 births; 24% of the births were to women
      aged > 34 years. Despite a higher prevalence of several risk factors for
      perinatal and infant death among the Amish, neonatal and infant death rates for
      Geauga Settlement Amish have been very similar to the corresponding rates for
      white children in rural Ohio and the state as a whole. The beneficial aspects of
      Amish society that may lessen the impact of perinatal risk factors on mortality
      merit further study.

PMID- 8296785
TI  - Prevalence of low birth weight among Hispanic infants with United States-born and
      foreign-born mothers: the effect of urban poverty.
AB  - Although Hispanics are a poorly educated and medically underserved minority, the
      incidence of low birth weight (less than 2,500 g) Hispanic infants is similar to
      that of non-Hispanic whites. The authors used 1982-1983 Illinois vital records
      and 1980 US census income data to determine the contribution of maternal nativity
      and place of residence to this epidemiologic paradox. The proportion of low birth
      weight Hispanic (n = 22,892) infants ranged from 4.3% for Mexicans to 9.1% for
      Puerto Ricans. Maternal age, education, trimester of prenatal care initiation,
      and place of residence were associated with the prevalence of low birth weight
      infants among Puerto Rican but not foreign-born Mexican or Central-South American
      mothers. In very low-income (less than $10,000/year) census tracts, Mexican and
      other Hispanic infants with US-born mothers had low birth weight rates of 14 and
      15%, respectively. In contrast, Mexican and other Hispanic infants with foreign
      born mothers who resided in these areas had low birth weight rates of 3 and 7%,
      respectively. In a logistic model that included only impoverished infants, the
      adjusted odds ratio of low birth weight for those with US-born mothers equalled
      6.3 (95 percent confidence interval 2.3-16.9). The authors conclude that urban
      poverty is negatively associated with Hispanic birth weight only when the mother
      is Puerto Rican or a US-born member of another subgroup.

PMID- 8296786
TI  - Proportional hazards analysis of diarrhea due to enterotoxigenic Escherichia coli
      and breast feeding in a cohort of urban Mexican children.
AB  - Ninety-eight women-infant pairs were followed for up to 50 weeks in the northern
      part of Guadalajara, Mexico, from August 1986 to July 1987 as part of a community
      based, prospective study of the relation between infant feeding patterns and
      enterotoxigenic Escherichia coli producing heat-labile toxin (LT-ETEC) diarrheal
      disease. Strictly formula-fed children had an incidence of diarrhea over three
      times that of strictly breast-fed infants and twice that of breast-fed and
      supplementally fed children. Strictly formula-fed infants colonized by LT-ETEC
      were symptomatic for diarrhea nearly three times as often as strictly breast-fed
      infants and twice as often as infants receiving a mixed diet. The fitting of
      parametric hazard models to durations until LT-ETEC colonization revealed that
      the hazard for the first colonization was time invariant. The hazard of diarrhea
      increased by 400-500% during the rainy season or among children 3 months of age
      or older who received avena, a barley drink. The best-fitting hazard models to
      durations until symptomatic expression of LT-ETEC infection all increased through
      time. This hazard was inversely impacted by the overall amount of LT-ETEC
      specific, immunoglobulin A antibodies the infant received via the mother's breast
      milk and by the provision of traditional medicinal teas.

PMID- 8296787
TI  - Attrition and use of proxy respondents and auxiliary information in the Sicilian
      Neuroepidemiologic Study.
AB  - Two-phase prevalence surveys with screening (phase 1) and examination (phase 2)
      are useful for some chronic diseases. Attrition, which may bias estimates, occurs
      in either phase because some eligible subjects die before contact, some refuse to
      cooperate, some are incapacitated, and some are unreachable. This investigation
      relates to a survey of neurologic diseases conducted in three municipalities of
      Sicily (prevalence date, November 1, 1987) and considers the attrition
      experienced and the use of proxy respondents in phase 1 and auxiliary information
      in phase 2 to offset, in part, this attrition. Regarding case finding, the
      salvage effort was more productive for decreased and incapacitated subjects. The
      age, sex, and household size of the subject were related to phase 1 attrition,
      but only age was related for all four attrition groups--deceased, refusing,
      incapacitated, and unreachable subjects. On the basis of information from proxy
      respondents, the educational levels of refusing and unreachable subjects were
      compared with those of subjects screened directly. Refusing subjects were less
      educated, and unreachable subjects were more educated. The proxy respondent
      performance, as indicated by "don't know" responses, was better with screening
      items concerning facial paralysis and mouth drooping (and not limb sensory
      abnormalities or impaired consciousness), better with younger subjects, and worse
      with refusing or incapacitated subjects.

PMID- 8296788
TI  - Re: "Confounding in studies of adverse reactions to vaccines".

PMID- 8296789
TI  - A new deletional alpha-thalassemia detected in Yemenites with hemoglobin H
      disease.
AB  - A new large deletion from the human alpha-globin gene cluster is characterized.
      It involves at least 39 kb and includes the two alpha-globin genes, the theta 1
      gene, all the pseudogenes, and the two hypervariable regions (HVRs), interzeta
      HVR and alpha-globin 3'HVR. The conserved zeta-globin gene has been identified in
      various restriction fragments of abnormal size. The new deletion was found in
      four unrelated Israeli patients with Hb H disease, all originating in Yemen, and
      has been designated--YEM. It is the only two-gene deletion identified in this
      ethnic group.

PMID- 8296790
TI  - von Willebrand's disease: use of collagen binding assay provides potential
      improvement to laboratory monitoring of desmopressin (DDAVP) therapy.
AB  - This report describes studies investigating the use of a collagen binding assay
      to improve the laboratory monitoring of desmopressin (DDAVP) therapy in patients
      with von Willebrand's disease (vWD). We evaluated the response of seven patients
      with vWD (four type I, three type IIA) to DDAVP, administered using a standard
      protocol, by assessing levels of von Willebrand factor (vWF) and factor VIII, as
      well as performing skin bleeding times (SBT) prior to, and at sequential time
      points following, DDAVP administration. The study employed the following assays:
      von Willebrand factor antigen assay (vWF:Ag; determined by ELISA); a novel
      functionally based collagen binding assay (CBA; determined by ELISA); ristocetin
      cofactor assay (RCof; determined by platelet aggregometry); von Willebrand factor
      multimer analysis (using SDS-agarose gels); factor VIII coagulant (FVIIIC;
      determined by clotting assay); and factor VIII antigen (FVIIICAG; determined by
      ELISA). All patients showed an initial incremental increase in vWF/FVIII levels
      using all assays above, and some showed some correction in SBT. Although the
      absolute levels of vWF/FVIII antigen or activity varied between patients, the CBA
      was found to provide consistently the greatest proportional incremental increases
      (i.e., -fold) compared to baseline (pre-DDAVP) levels. Accordingly, we
      consistently observed an increase in the CBA to vWF:Ag ratio for all patients
      evaluated. This supplements previous findings that have suggested a unique
      ability of our CBA procedure to bind preferentially to higher molecular weight
      (i.e., more functionally active) forms of vWF. We therefore propose that the use
      of the above test combination (e.g., vWF:Ag plus CBA) may provide the basis for
      more accurate estimation of a patient's functional responsiveness to DDAVP
      therapy in future studies.

PMID- 8296791
TI  - Detection of PML-retinoic acid receptor-alpha fusion transcripts in acute
      promyelocytic leukemia with trisomy 8 but without t(15;17).
AB  - Chromosome translocation t(15;17), the breakpoints of which are in the PML gene
      on chromosome 15 and retinoic acid receptor-alpha (RAR alpha) gene on chromosome
      17, is specifically found in acute promyelocytic leukemia (APL). Clinically
      typical APL without t(15;17) and with the PML-RAR alpha fusion transcripts or
      rearrangements in PML and/or RAR alpha gene has been reported, suggesting
      submicroscopic changes at the molecular level without apparent t(15;17) or
      observation of normal metaphases. Trisomy 8 is common in APL as a secondary
      chromosomal abnormality in addition to t(15;17), as well as in acute myelogenous
      leukemia in general, but it is rare as a sole chromosomal anomaly in APL. PML-RAR
      alpha fusion transcript was detected in an APL case with trisomy 8 but without
      t(15;17), indicating that the leukemic cells lacked t(15;17) and still expressed
      the PML-RAR alpha fusion transcripts. This indicates that the same submicroscopic
      molecular changes as in APL with t(15;17) do occur in APL without t(15;17) and
      supports the use of molecular analysis for PML-RAR alpha fusion in APL.

PMID- 8296792
TI  - Stability of factor VIII concentrates after reconstitution.
AB  - Adjusted-dose continuous infusion of factor VIII (F VIII) has recently been shown
      to reduce the doses of the factor in patients undergoing surgery by 50-75%. The
      main limitation of this method has been the instability of factor concentrates.
      All manufacturers are recommending infusion of the concentrate within hours after
      reconstitution. We studied the stability of 15 different lyophilized F VIII
      products. Reconstituted samples were stored for periods of 4, 24, and 72 hr and
      1, 2, 3, and 4 weeks at temperatures of 4-8 degrees C, 20-23 degrees C, and 37
      degrees C in their original glass containers and in plastic tubes and then
      frozen. Assays were performed in duplicate, using a one-stage clotting method and
      a chromogenic assay for F VIII, with all samples from a single concentrate in the
      same run. Activation of the coagulation factor occurred in some concentrates,
      more often at 4-8 degrees C than at 20-23 degrees C or 37 degrees C. The
      stability of all products was substantially better than that declared by the
      manufacturers. Several concentrates maintained factor activities above 80% of
      baseline for the entire period of 4 weeks at 4-8 degrees C or at 20-23 degrees C.
      The results demonstrate that many of the F VIII concentrates may be used for
      continuous infusion.

PMID- 8296793
TI  - Effects of interleukin-2 administration on platelet function in cancer patients.
AB  - Platelet function in 16 patients with metastatic renal cell carcinoma and
      melanoma was studied sequentially over the first 96 hr of treatment with moderate
      and high-dose interleukin-2 (IL-2). During the first 96 hr of therapy, an
      increased ex vivo platelet maximal aggregation (MA) response to ADP, epinephrine,
      and arachidonic acid was paralleled by a decrease in the peripheral platelet
      count. Plasma specimens from patients receiving the moderate dose schedule showed
      a significant IL-2 induced secretory response of the platelet alpha-granule
      components beta-thromboglobulin (BTG) and platelet factor 4 (PF4) and the
      eicosanoid thromboxane B2 (TBX2) as measured by RIA. The increase in TXB2 was
      highly correlated with MA when analyzed by bivariate regression analysis, whereas
      the addition of PF4 to TXB2 in a multiple regression analysis further increased
      their correlation to MA. The observed decrease in peripheral platelet count
      correlated significantly with MA and PF4 secretion. High-dose IL-2-treated
      patients showed a statistically significant increase in the percentage of large
      platelets exceeding 12 fl in diameter and platelet responsiveness to hypotonic
      shock. These observations suggest that IL-2 therapy results in a reduced
      peripheral platelet pool, with an increased proportion of the remaining pool of
      platelets larger, more viable, and activated.

PMID- 8296794
TI  - Elevated plasma tissue factor antigen level in patients with disseminated
      intravascular coagulation.
AB  - The plasma tissue factor (TF) antigen level was measured in patients with
      disseminated intravascular coagulation (DIC). The plasma TF antigen was detected
      in normal volunteers, and it was significantly higher in DIC patients than in non
      DIC patients. However, in some patients with DIC, the plasma TF antigen level was
      within the normal range. The plasma TF antigen level in patients with DIC
      significantly decreased after therapy, but it was not correlated with organ
      failure or outcome. The plasma TF antigen level in patients with DIC was not
      correlated with other hemostatic markers. The plasma TF antigen level tended to
      be higher in DIC patients with nonlymphoid leukemia than in those with lymphoid
      tumor. TF might be implicated in the occurrence and progression of DIC.

PMID- 8296795
TI  - Erythropoietin in the treatment of delayed immune hemolysis of a major ABO
      incompatible bone marrow transplant.
AB  - Delayed immune hemolysis can be observed after major ABO-incompatible bone marrow
      transplants (BMT). The management of these hemolytic episodes includes
      transfusion of group O red blood cells and increases of immunosuppression. Here
      we report the case of a 25-year-old patient who developed overt immune hemolysis
      on day +50 after a HLA-identical ABO-incompatible BMT. To avoid added
      immunosuppression, erythropoietin was started: an increase in reticulocytes
      sufficient to maintain hemoglobin despite persistent hemolysis was observed. We
      conclude that erythropoietin may have a role in the management of delayed-onset
      hemolysis of major ABO-incompatible BMT, especially when added immunosuppression
      is undesirable.

PMID- 8296796
TI  - Spontaneous factor VIII inhibitor occurring in association with chronic graft
      versus-host disease.
AB  - The development of spontaneously acquired Factor VIII inhibitors is rare and may
      lead to serious hemorrhagic sequelae. We report here the case of a patient who
      acquired a Factor VIII inhibitor two years after an allogeneic bone marrow
      transplant for CML. This occurred in association with a flare of chronic graft
      versus host disease (GVDH). He responded to corticosteroid therapy. A review of
      autoimmune phenomena associated with chronic GVDH and the treatment of Factor
      VIII inhibitors is discussed.

PMID- 8296797
TI  - Malignant histiocytosis associated with autoimmune thrombocytopenia.
AB  - We describe a patient with malignant histiocytosis whose serum contained an
      autoantibody against platelet protein. The patient was admitted because of nasal
      bleeding and high-grade fever. The clinical course was fulminantly progressive
      and terminated with cerebral hemorrhage. Bone marrow aspirate showed the
      proliferation of large atypical cells, some of which exhibited phagocytic
      activity. At postmortem examination, there was diffuse infiltration of these
      atypical cells in the liver, spleen, kidney, and bone marrow. Morphological,
      cytochemical, immunohistochemical, and genotypic characteristics suggested that
      the proliferating cells were derived from the monocyte-macrophage system. Western
      blot analysis revealed the presence of autoantibody against an approximately 88
      kd molecule of platelet proteins. Although the relationship of cause and effect
      remains to be clarified, this autoantibody appeared to have stimulated
      thrombophagocytosis of the neoplastic cells.

PMID- 8296798
TI  - alpha-Interferon treatment for idiopathic hypereosinophilic syndrome.
AB  - Idiopathic hypereosinophilic syndrome (HES) is a poorly understood disorder
      characterized by a markedly elevated peripheral blood eosinophil count in the
      absence of known associated causes of hypereosinophilia. Idiopathic
      hypereosinophilic syndrome is associated with eosinophil-induced organ damage,
      including endomyocardial and pulmonary fibrosis, stroke, and gastrointestinal
      disease. Treatment of idiopathic HES is centered on the reduction of peripheral
      circulating eosinophils in an effort to diminish tissue infiltration and
      destruction. Multiple cytotoxic agents have been tried, with variable results.
      Prednisone and hydroxyurea have remained the therapies of choice in long term
      treatment of idiopathic HES. We report here the successful 2 year treatment of
      aggressive idiopathic HES, refractory to hydroxyurea and prednisone, with alpha
      interferon.

PMID- 8296799
TI  - Thrombocytopenia following acute acetaminophen overdose.
AB  - An unusual case of severe thrombocytopenia following acetaminophen overdose is
      presented along with a retrospective review of 174 patients with hospital
      admissions for acute acetaminophen toxicity. Thrombocytopenia occurred in 3.4% of
      these patients and strongly correlated with the degree of hepatotoxicity (as
      measured by peak AST values) but did not correlate with serum acetaminophen
      levels. The mechanism appears to be a transient direct toxic effect on platelets
      or megakaryocytes, and the finding of thrombocytopenia early in the course of
      acetaminophen overdose may identify a subset of patients at risk for significant
      hepatotoxicity.

PMID- 8296800
TI  - Hereditary hemochromatosis and red cell aplasia.
AB  - A 63-year-old white man with myasthenia gravis and red cell aplasia was found to
      have hepatic iron overload. The differential diagnosis included hereditary
      hemochromatosis and secondary iron overload related to red cell aplasia. Family
      studies of siblings, including HLA typing, initially suggested a diagnosis of
      secondary iron overload. The investigation of a remote sibling led to the final
      diagnosis of hereditary hemochromatosis. The case illustrates the importance of
      complete family investigations in the differentiation between hereditary
      hemochromatosis and secondary iron overload and the potential hazard of using HLA
      typing as an indirect genetic test for hereditary hemochromatosis.

PMID- 8296801
TI  - IgE plasma cell leukemia successfully treated with combination VAD (vincristine,
      doxorubicin, dexamethasone) and MP (melphalan, prednisolone) followed by
      interferon-alpha.
AB  - A 69-year-old woman with IgE/kappa plasma cell leukemia (PCL) was treated with a
      sequential combination of VAD (vincristine, doxorubicin, dexamethasone) and MP
      (melphalan, prednisolone) followed by interferon-alpha (IFN alpha). A complete
      remission was achieved for 14 months. Maintenance therapy with IFN alpha has
      continued for an additional 10 months. IgE PCL is extremely rare. The biological
      characteristics of the myeloma cells, including surface marker, adhesion
      molecule, karyotype, DNA analysis, and the response to various cytokines, are
      presented.

PMID- 8296802
TI  - Lung perfusion scanning in two patients with malignant histiocytosis.

PMID- 8296803
TI  - Good response to high-dose intravenous immunoglobulin in patients with alveolar
      hemorrhage refractory to platelet transfusion.

PMID- 8296804
TI  - Common acute lymphoblastic leukemia antigen (CD10)-positive Sezary's syndrome.

PMID- 8296805
TI  - Acquired platelet storage pool deficiency due to severe valvular disease
      corrected by prosthetic valve replacement.

PMID- 8296806
TI  - Detection of human T lymphotropic virus type I proviral DNA in fresh cells from
      ascitic fluid in a patient with adult T-cell leukemia.

PMID- 8296807
TI  - Parvovirus B19 infection causing severe peripheral blood thrombocytopenia and
      persistent viremia.

PMID- 8296808
TI  - Ethics in gynecologic surgical innovation.
AB  - J. Marion Sims' efforts in surgically curing vesicovaginal fistula are retold.
      The controversy surrounding his surgical innovation on black slaves is discussed
      in the context of the ethical principles of autonomy, beneficence, and justice.
      The relevance of his story to modern surgical innovation in incontinence surgery
      is emphasized in a discussion of the Pereyra, Gittes, and paravaginal procedures.
      A call is made to establish a gynecologic ethic to ensure that patients' rights
      are respected in all future surgical innovation.

PMID- 8296809
TI  - Tocolysis with indomethacin increases the incidence of necrotizing enterocolitis
      in the low-birth-weight neonate.
AB  - OBJECTIVE: The null hypothesis states that prolonged antenatal indomethacin
      exposure within 24 hours of delivery does not increase the incidence of
      necrotizing enterocolitis in the low-birth-weight neonate. STUDY DESIGN: The
      neonates of patients receiving indomethacin tocolysis admitted in preterm labor
      (N = 56) were compared with the neonates of preterm labor patients who received
      no indomethacin tocolysis (N = 703). These neonatal groups were then compared
      with regard to gestational age at delivery, birth weight, mode of delivery,
      antenatal magnesium and steroid exposure, incidence of respiratory distress
      syndrome, perinatal depression, sepsis, umbilical catheterization, and feeding
      rates and volumes. The overall incidence of necrotizing enterocolitis, mortality
      secondary to necrotizing enterocolitis, and the intervals from delivery and
      feeding to necrotizing enterocolitis diagnosis were also compared. The
      association between necrotizing enterocolitis and the duration of indomethacin
      exposure and the interval from exposure to delivery for both the indomethacin and
      control groups was determined. RESULTS: The incidence of necrotizing
      enterocolitis in neonates who were delivered within 24 hours of maternal
      indomethacin therapy was 20% compared with 9% in the control group (p = 0.005).
      The incidence of necrotizing enterocolitis in neonates with > 48 hours of
      antenatal indomethacin exposure was 26.4% compared with 4.1% in those with < 48
      hours exposure (p = 0.042). The interval from first feeding to necrotizing
      enterocolitis development was significantly shorter in the indomethacin group
      versus the control group (2.1 +/- 3.0 vs 6.8 +/- 6.3 days) (p = 0.001), as was
      the mean interval from delivery to development of necrotizing enterocolitis (10.2
      +/- 3.7 vs 15.2 +/- 3.8 days) (p = 0.019). CONCLUSIONS: Antenatal indomethacin
      exposure occurring within < or = 24 hours of delivery and of at least 48 hours'
      duration is associated with a significant increase in the incidence of
      necrotizing enterocolitis in the low-birth-weight neonate.

PMID- 8296810
TI  - Left ventricular systolic and diastolic function in pregnant patients with sickle
      cell disease.
AB  - OBJECTIVE: Our purpose was to document noninvasively the effect of sickle cell
      disease on left ventricular systolic and diastolic function during the third
      trimester of pregnancy. STUDY DESIGN: Fifteen patients with sickle cell disease
      underwent a two-dimensional M-mode echocardiography obtained using the long axis
      with the cursor placed at the level of the tip of the mitral valve. All studies
      were performed with the patient in the left lateral decubitus. A group of 40
      normal pregnant patients served as controls. None of the patients had evidence of
      cardiovascular disease. Left atrial and ventricular dimensions and mass were
      calculated and averaged. Left ventricular systolic and diastolic function were
      assessed. RESULTS: Pregnant patients with sickle cell disease had a significant
      enlargement of the left ventricular end-diastolic dimension, posterior wall,
      interventricular septum, and ventricular mass than the control group. Although
      heart rate and fractional shortening were not different between the two groups,
      stroke volume and cardiac output were higher in patients with sickle cell
      disease. This was mostly because of enlargement of left end-diastolic dimension.
      Ventricular diastolic function was different in patients with sickle cell
      disease, resulting in an increase in the duration of the rapid filling.
      CONCLUSION: Left ventricular systolic function in patients with sickle cell
      disease was not affected in spite of a marked ventricular hypertrophy and
      ventricular enlargement. Diastolic function, however, was lower in the sickle
      cell group, which indicates a decrease in ventricular compliance. These patients
      had a higher cardiac output than did a normal pregnant group in the third
      trimester. This was accomplished by increasing ventricular size without
      increasing heart rate or fractional shortening.

PMID- 8296811
TI  - Anatomic abnormalities of the retroperitoneum encountered during aortic and
      pelvic lymphadenectomy.
AB  - OBJECTIVE: Our purpose was to describe retroperitoneal abnormalities and related
      surgical problems encountered during lymphadenectomy. STUDY DESIGN: A prospective
      study was carried out on 309 consecutive patients with cervical, endometrial, and
      ovarian cancer treated with systematic aortic and pelvic lymphadenectomy at the
      Department of Gynecological Oncology of the Catholic University, Rome. RESULTS:
      Urinary and vascular anomalies were observed in five (1.6%) and 42 (13.6%) cases,
      respectively. Preoperative diagnosis was made by intravenous pyelography and
      computed tomographic scan in 14.9% (seven of 47) of patients with malformations.
      In three cases abnormal vessels were accidentally injured during lymphadenectomy
      with no postoperative sequelae. CONCLUSIONS: Preoperative diagnosis of
      retroperitoneal abnormalities is rarely made during routine preoperative workup.
      Thus during surgery an accurate surgical technique including adequate exposure of
      retroperitoneal organs and careful blunt dissection together with a knowledge of
      both normal and abnormal anatomy are necessary to avoid accidental injury to
      abnormal retroperitoneal organs.

PMID- 8296812
TI  - Noninvasive measurement of platelet kinetics in normal and hypertensive
      pregnancies.
AB  - OBJECTIVE: Our purpose was to determine platelet kinetics in pregnancy by means
      of noninvasive reticulated platelet counts and to examine in a pilot study
      whether increased reticulated platelet values were associated with preeclampsia
      and pregnancy-induced hypertension. STUDY DESIGN: Nulliparous women had blood
      samples drawn at enrollment (first prenatal visit) and at 28 and 36 weeks'
      gestation. The percent of reticulated platelets (an index of marrow platelet
      release correlating with increased thrombopoiesis), platelet-associated
      immunoglobulin, and serum antiplatelet antibody were measured and correlated with
      the clinical course for each patient. RESULTS: In 31 normal pregnancies the
      percent of reticulated platelets was never significantly higher than the values
      for normal nonpregnant women (5.8% +/- 2.2%) in spite of a significant decrease
      in platelet count by 36 weeks. By contrast, the percent of reticulated platelets
      in four women with preeclampsia rose significantly to 13.9% +/- 11.2% at 28
      weeks, before the onset of clinical signs. No women had evidence of immune
      platelet destruction. CONCLUSION: In normal pregnancy the decline in platelet
      count is not accompanied by an increase in marrow platelet production, suggesting
      that the platelet decrease is dilutional without a compensatory thrombopoietic
      response or alternatively that thrombopoiesis is down-regulated during normal
      pregnancy. However, platelet production does increase before the onset of
      symptoms in a small number of women in whom preeclampsia or pregnancy-induced
      hypertension subsequently develops. These findings may justify a larger
      prospective study to determine whether noninvasive serial measurement of the
      percent of reticulated platelets can predict those pregnant women at risk for
      hypertension and preeclampsia.

PMID- 8296813
TI  - The bioethics of human fetal tissue research and therapy: moral decision making
      of professionals.
AB  - OBJECTIVE: We investigated the decision making of professionals regarding the
      ethical acceptability of using human fetal tissue from elective abortion for
      research or therapy. STUDY DESIGN: We surveyed 390 professionals from 20 European
      countries on their ethical beliefs regarding the scientific and medical use of
      human fetal tissue from elective abortion. We assessed the importance of basic
      medical ethics and beliefs regarding the morality of abortion and fetal rights to
      their decision making. RESULTS: Sixty-six percent of 198 responding professionals
      believed that use of fetal tissue from elective abortion was ethically
      acceptable. Beliefs regarding the morality of elective abortion and fetal
      exploitation overwhelmingly influenced individual ethics regarding fetal tissue
      research or therapy. CONCLUSION: Ethical decision making is a dynamic process and
      individuals are not altogether consistent in their beliefs. The important public
      policy issues raised in this study concern the rights of the dead fetus, whether
      these rights are exploited through fetal tissue therapy, and whether women's
      right of authority over the disposition of aborted fetal tissue is abdicated.

PMID- 8296814
TI  - A comparative study of the effect of high-intensity transcutaneous nerve
      stimulation and oral naproxen on intrauterine pressure and menstrual pain in
      patients with primary dysmenorrhea.
AB  - OBJECTIVE: Our purpose was to compare the effects of high-intensity
      transcutaneous electrical nerve stimulation and oral naproxen (500 mg) on
      intrauterine pressure and menstrual pain. STUDY DESIGN: An open, randomized
      crossover study was performed on 12 women with primary dysmenorrhea. Intrauterine
      pressure was recorded with a microtransducer catheter, and the pain score was
      assessed by a visual analog scale. RESULTS: Before treatment all patients
      displayed signs of uterine hyperactivity as judged by a high resting pressure
      (7.5 +/- 0.4 kPa), high active pressure (24.0 +/- 0.8 kPa), and a high frequency
      of pressure cycles (13.3 +/- 0.5 contractions per 0.5 hour). Oral administration
      of naproxen suppressed (p < 0.01) all uterine activity parameters. Treatment with
      transcutaneous electrical nerve stimulation induced a prompt onset of pain relief
      in a strictly segmental manner, but there were no significant changes in uterine
      activity. The pain score was significantly reduced (p < 0.001) from 30 to 60
      minutes after treatment with transcutaneous electrical nerve stimulation and from
      19 to 120 minutes after naproxen administration. CONCLUSIONS: Treatment with
      transcutaneous electrical nerve stimulation induced a prompt onset of pain relief
      without any significant changes in uterine activity. Possible mechanisms for the
      pain relief, decreased uterine ischemia or decreased activity in the pain
      transmission system at spinal or supraspinal levels, are discussed.

PMID- 8296815
TI  - Urinary dipstick protein: a poor predictor of absent or severe proteinuria.
AB  - OBJECTIVE: Our purpose was to compare urinary protein dipstick values with
      standard 24-hour urinary protein excretion in women with hypertension in
      pregnancy. STUDY DESIGN: Urinary protein dipstick determinations and concurrent
      24-hour urinary protein excretion measurements were compared by review of 300
      urine samples obtained from women with hypertension in pregnancy. RESULTS: One
      hundred twenty-three samples had negative to trace protein on dipstick on two
      occasions at least 6 hours apart. Eight-one (66%) of these patients had
      significant proteinuria (> or = 300 mg per 24 hours). Seventy-six samples
      revealed 3+ to 4+ protein on dipstick in at least two samples. Of these, 27 (36%)
      had heavy proteinuria (> or = 5 gm per 24 hours), and 42 (55%) had nephrotic
      range proteinuria of > or = 3.5 gm per 24 hours. One hundred one patients had
      urine dipstick values of 1+ to 2+, of whom 89 (88%) had significant proteinuria.
      CONCLUSION: Urinary protein dipstick values > or = 1+ have a positive predictive
      value of 92% (162/177) for predicting > or = 300 mg per 24 hours. In contrast, a
      dipstick of negative to trace should not be used to rule out significant
      proteinuria because its negative predictive value is only 34% (42/123) in
      hypertensive patients. Moreover, urine dipstick values of 3+ to 4+ should not be
      used to diagnose severe preeclampsia because their positive predictive value is
      only 36% (27/76).

PMID- 8296816
TI  - Instruction in surgical anatomy for gynecology residents using prosected human
      cadavers.
AB  - Prosected human cadavers were used by a team of anatomists and gynecologic
      surgeons to teach surgical anatomy to gynecology residents. The course was
      offered at the start of each 8-week gynecologic surgery rotation. Hemisections
      and other similar prosections were used to demonstrate anatomic relationships and
      surgical procedures from vantage points unobtainable at the operating table. The
      initial response from the faculty and residents was encouraging. The residents
      believed the program to be beneficial and were satisfied with it. Both the
      anatomy faculty and the gynecology faculty found new insights into teaching
      issues during the interdisciplinary process of course preparation and teaching.

PMID- 8296817
TI  - Localization and timing of appearance of insulin, insulin-like growth factor-I,
      and their receptors in the human fetal mullerian tract.
AB  - OBJECTIVE: The factors that regulate fetal mullerian tract development are still
      unknown. Insulin and insulin-like growth factor-I are peptides postulated to
      serve as autocrine or paracrine regulators of cell activity. We have previously
      demonstrated that messenger ribonucleic acid for insulin and insulin-like growth
      factor-I receptors are expressed in fetal uterine tissues. We undertook this
      study to determine by immunohistochemical techniques the exact location of these
      two growth factors and their receptors in the human fetal uterus. STUDY DESIGN:
      We obtained freshly discarded human fetal uteri (n = 12) between 15 and 22 weeks
      of gestation from elective pregnancy terminations. Frozen-section specimens were
      incubated with antibodies against insulin, insulin-like growth factor-I, insulin
      receptor, and insulin-like growth factor-I receptor. These sections were then
      incubated with a second antibody conjugated to fluorescein isothiocyanate and
      examined under phase and fluorescent microscopy. RESULTS: The fetal endometrium
      at 19 and 22 weeks of gestation contained insulin, insulin-like growth factor-I,
      insulin receptor, and insulin-like growth factor-I receptor. The distribution of
      immunofluorescence in the endometrium is similar for both insulin and its
      receptor. The same pattern of immunostaining was likewise demonstrated for
      insulin-like growth factor-I and its receptor. CONCLUSION: The localization of
      these growth factors and their receptors, combined with our previous messenger
      ribonucleic acid data, suggest an autocrine or paracrine role for insulin and
      insulin-like growth factor-I in the developing human fetal mullerian tract.

PMID- 8296818
TI  - Regional blood flow in asphyxiated fetuses with seizures.
AB  - OBJECTIVE: Our purpose was to determine ovine fetal regional blood flow changes
      during asphyxia of such severity that it results in seizures. STUDY DESIGN: Six
      ovine fetuses were exposed to severe asphyxia produced by maternal uterine artery
      occlusion for up to 90 minutes. Fetal blood pressure and heart rate, blood gases,
      acid base status, electrocorticogram, electromyogram and regional blood flow
      (radioactive microspheres) measurements were recorded. RESULTS: During the
      asphyxial insult pH fell from 7.39 +/- 0.01 (mean +/- SEM) to 6.99 +/- 0.01 at 60
      minutes, base excess from 4 +/- 1 to -16 +/- 1 mEq/L, and oxygen content from 3.5
      +/- 0.4 to 0.5 +/- 0.1 mmol/L (p < 0.05). There was no significant change in
      fetal heart rate or blood pressure. The fetal electrocorticogram was profoundly
      suppressed during asphyxia, and seizure activity began 50 +/- 19 minutes after
      the release of occlusion in all surviving animals. Blood flow increased to the
      heart and adrenals during asphyxia and decreased to spleen, gut, kidneys, and
      carcass (p < 0.05). There was no change in combined ventricular output and
      umbilical blood flow. There was no significant increase in total cerebral
      perfusion. CONCLUSION: When the ovine fetus is exposed to asphyxia of sufficient
      severity to produce neurologic damage (seizures), the pattern of redistribution
      of blood flow is comparable to the response to lesser asphyxia, except that a
      significant increase in total brain blood flow does not occur. This finding may
      have an important association with the development of long-term neurologic
      damage.

PMID- 8296819
TI  - Parallel mechanisms of Ca++ transfer across the perfused human placental
      cotyledon.
AB  - OBJECTIVES: We dissected the paracellular and transcellular components of Ca++
      transfer across the perfused human placental cotyledon and explored the nature of
      the transcellular component. STUDY DESIGN: Transfer of 45Ca++ and
      ethylenediaminetetraacetic acid labeled with chromium 51 was measured across the
      in vitro perfused cotyledon of the human placenta, and paracellular and
      transcellular components of the transfer of Ca++ were calculated from the
      transfer of the two tracers. RESULTS: The transcellular component of the Ca++
      transfer in the maternal-fetal direction represented about one third of the total
      maternal-fetal transfer. It was saturable, sensitive to cyanide, and insensitive
      to verapamil. The transcellular component in the fetal-maternal direction was not
      different from zero. The in vitro transfer rates correlated well with the
      transfer rates estimated for the in vivo situation from data published in the
      literature. CONCLUSION: There is a significant active transport of Ca++ across
      the human placenta in the maternal-fetal direction.

PMID- 8296821
TI  - Further studies of the role of surfactant in premature rupture of the membranes.
AB  - OBJECTIVE: The purpose of this study was to assess the hypothesis that surface
      active phospholipid (i.e., amniotic surfactant) plays a major role in maintaining
      the mechanical integrity of the chorioamniotic sac. STUDY DESIGN: Three studies
      were designed using chorioamniotic sacs from normal term deliveries. First, it
      was demonstrated how the extreme hydrophobicity (and lubricity) of amniotic and
      chorionic epithelium could be greatly reduced by incubating the membrane with
      bile salts, which react with surface-active phospholipid. Second, hydrophobic
      probes were used under epifluorescence microscopy to identify any structured
      surface-active phospholipid. Third, electron microscopy was used to investigate
      the ultrastructure, by means of a novel fixation procedure that does not destroy
      hydrophobic interfaces. RESULTS: Both morphologic studies confirmed planar
      structures of oligolamellar surface-active phospholipid running parallel to the
      membrane that contained lamellar bodies. CONCLUSION: These sheets of surface
      active phospholipid could be very cohesive within the planes, thus improving
      tensile strength while promoting shearing between planes to provide the type of
      lubrication afforded by graphite whose ultrastructure they closely resemble.

PMID- 8296820
TI  - Effects of inhibition of prostaglandin synthesis on flow and composition of fetal
      urine, lung liquid, and swallowed fluid in sheep.
AB  - OBJECTIVE: Our aim was to determine the effects of blocking prostaglandin
      synthesis, by infusion of indomethacin into the fetal circulation, on factors
      regulating amniotic fluid volume and on plasma composition in the mother and
      fetus. STUDY DESIGN: Indomethacin was administered to fetal sheep during 8 hours
      at 124.0 +/- 1.2 days of gestation (n = 7) and at 134.7 +/- 0.8 days of gestation
      (n = 7) (term approximately 147 days). Vehicle infusions were performed at 128.8
      +/- 1.4 days of gestation (n = 5). RESULTS: Fetal urine production was
      significantly reduced and both fetal urine osmolality and plasma arginine
      vasopressin concentrations were significantly elevated in response to
      indomethacin infusions at both gestational ages. Fetal blood and urine lactate
      concentrations were elevated in response to indomethacin. Later in gestation,
      fetal lung liquid flow was significantly changed from a net efflux to a net
      influx. There was no significant effect of indomethacin on the volume of fluid
      swallowed by the fetus. CONCLUSION: Inhibition of fetal prostaglandin synthesis
      profoundly reduces the production of the two major fetal fluids contributing to
      amniotic fluid, namely, urine and lung liquid. These findings may explain why
      indomethacin reduces amniotic fluid volume.

PMID- 8296822
TI  - Fetal fibronectin in patients at increased risk for premature birth.
AB  - OBJECTIVE: The objective of this study was to evaluate fetal fibronectin as a
      screening test for subsequent preterm birth in asymptomatic pregnant women. STUDY
      DESIGN: Eighty-seven pregnant women at increased risk for preterm birth underwent
      weekly sampling of cervicovaginal secretions beginning in the middle of the
      second trimester and continuing until delivery or until 34 weeks of gestation,
      with quantitative measurement for fetal fibronectin. In addition, assessment of
      cervical dilatation, uterine activity, and tocolytic therapy was performed with
      each sampling. Preterm birth was the specific outcome measured, and the
      correlation of fetal fibronectin with this outcome was determined. RESULTS:
      Overall, 31% of the patients experienced a spontaneous preterm birth. As a
      predictor for delivery before 37 completed weeks of gestation, the presence of
      fetal fibronectin had a sensitivity of 92.6%, a specificity of 51.7%, a positive
      predictive value of 46.3%, and a negative predictive value of 93.9%. For delivery
      before 34 weeks, fetal fibronectin had a sensitivity of 92.3% and a negative
      predictive value of 97.8%. By means of logistic regression analysis a positive
      fetal fibronectin result was highly significantly correlated with preterm birth
      (odds ratio 3.8, p < 0.001) and more so than the presence of four or more uterine
      contractions per hour, tocolytic therapy, or cervical dilatation of > or = 2 cm.
      The addition of contractions, tocolytic therapy, or cervical dilatation to a
      positive fetal fibronectin result did not increase the predictive capacity of a
      positive fetal fibronectin alone. CONCLUSION: Fetal fibronectin in the
      cervicovaginal secretions of asymptomatic patients has potential value as a
      screening test in the identification of patients at risk for preterm birth. This
      test had equally high sensitivity and negative predictive value for birth before
      37 weeks.

PMID- 8296823
TI  - Transferrin receptor (CD71) expression on circulating mononuclear cells during
      pregnancy.
AB  - OBJECTIVE: We studied transferrin receptor (CD71) expression in peripheral blood
      mononuclear cells from healthy pregnant women, to determine if a relationship
      existed between gestational age and circulating CD71+ mononuclear cells. STUDY
      DESIGN: Cell suspensions were prepared from venous blood from 139 pregnant women
      (7 to 26 weeks of gestation), incubated with monoclonal anti-CD71 antibody, and
      analyzed by flow cytometry. RESULTS: When only the first sample from each woman
      was analyzed, extensive biologic variation between women was shown. An apparent
      biphasic increase in the percentage of CD71+ cells with advancing gestation was
      suggested. A subgroup of 13 women studied on multiple occasions demonstrated
      linear increases in CD71+ cells as pregnancy progressed. CONCLUSIONS: Pregnant
      women, when compared with each other, may have differences in the baseline number
      of circulating CD71+ cells. The increases seen in individuals studied repeatedly
      are likely to reflect maternal hematopoiesis and current fetomaternal
      transfusion.

PMID- 8296824
TI  - Increased vulnerability to neuronal damage after umbilical cord occlusion in
      fetal sheep with advancing gestation.
AB  - OBJECTIVE: The purpose of this study was to compare systemic responses and
      neurologic consequences of umbilical cord occlusion in fetal sheep with advancing
      gestation. STUDY DESIGN: The umbilical cord was occluded for 10 minutes in nine
      midgestation (90 to 92 days) and 10 late-gestation (135 to 136 days) chronically
      instrumented fetuses. Systemic and cortical electrophysiologic effects were
      compared by analysis of variance. The extent of neuronal loss was determined 3
      days later. RESULTS: During occlusion, hypotension (23 +/- 2 mm Hg) and cortical
      cytotoxic edema were more marked in older fetuses (p < 0.001). On reperfusion,
      the edema, rebound tachycardia, and hypertension resolved within 20 minutes.
      Recovery of electroencephalographic activity (3.1 +/- 0.8 hours) and lactate
      levels (> 2 hours) was slower in late-gestation fetuses (p < 0.05). Neuronal
      loss, which was observed only in the older group, was predominantly in the
      hippocampus and was associated with the severity of hypotension during umbilical
      occlusion but not with systemic lactate levels. CONCLUSION: Late-gestation fetal
      sheep are neurologically more susceptible to umbilical cord occlusion than are
      midgestation fetal sheep. Possibly the lesser ability of the older fetuses to
      maintain blood pressure and cerebral plasma membrane function during asphyxia
      contributes to the greater vulnerability in the gray matter.

PMID- 8296825
TI  - Lipid peroxidation increases arterial cyclooxygenase activity during pregnancy.
AB  - OBJECTIVE: We tested the hypothesis that increased production of lipid peroxides
      (induced by a mild vitamin E deficiency) during pregnancy would alter the
      cyclooxygenase pathway of arachidonate metabolism, resulting in impaired
      endothelial-dependent vascular function. STUDY DESIGN: Mesenteric arteries from
      pregnant control (n = 12) and pregnant vitamin E-deprived (n = 12) Sprague-Dawley
      rats were studied in a myograph. RESULTS: Surprisingly, endothelial-dependent
      relaxations to methacholine were enhanced in arteries from the pregnant vitamin E
      deprived rats compared with the pregnant control rats (mean effective
      concentration producing a 50% response = 0.034 vs 0.046 mumol/L, p < 0.05). In
      the arteries from the vitamin E-deprived rats this enhanced response was blunted
      and the group difference eliminated in the presence of a cyclooxygenase inhibitor
      (1 mumol/L meclofenamate, mean effective concentration producing a 50% response
      0.057 vs 0.034 mumol/L, p < 0.05) but had no effect on the arteries from the
      control pregnant rats. The thromboxane A2-prostaglandin H2 receptor blocker (1
      mumol/L SQ 29548) had no effect on the arteries from either group. Endothelial
      independent relaxations to sodium nitroprusside were not affected by vitamin E
      deprivation. Arachidonic acid elicited less tension in the arteries from the
      vitamin E-deprived rats compared with the controls (at 10 mumol/L: 0.41 vs 0.90
      mN/mm, p < 0.01). Cyclooxygenase inhibition potentiated the vasoconstrictor
      response only in the arteries from the vitamin E-deprived rats (at 10 mumol/L:
      0.92 vs 0.41 mN/mm, p < 0.01) so that the group difference was eliminated.
      CONCLUSION: An elevation of lipid peroxides, mediated by a mild vitamin E
      deprivation, resulted in an increased cyclooxygenase-dependent vasorelaxation in
      the mesenteric arteries of the pregnant rat.

PMID- 8296826
TI  - Permeation of human chorioamniotic membranes by Escherichia coli in vitro.
AB  - OBJECTIVE: Our goal was to study the permeation of Escherichia coli through human
      chorioamniotic membranes in vitro. STUDY DESIGN: Medium was placed in two
      compartments separated by chorioamniotic membranes obtained from six cesarean
      sections at term. The compartment faced by the chorion was inoculated with E.
      coli. Both compartments were sampled over 12 hours for observation of bacterial
      growth. Controls were performed without membranes. RESULTS: In the compartment
      that was inoculated, concentration of E. coli increased from 10(6) to 10(10)
      colony-forming units per milliliter. In the compartment faced by amnion,
      bacterial growth was observed after 6 hours and reached 10(3) colony-forming
      units per milliliter. Permeation of E. coli was confirmed histopathologically.
      The change of glucose and lactate was linear. In the controls the concentration
      of E. coli increased to 10(7) (p < 0.001). CONCLUSIONS: E. coli organisms
      permeate viable chorioamniotic membranes. The membranes constitute a weak barrier
      against ascending infection and do not inhibit bacterial growth.

PMID- 8296827
TI  - Rat embryo development on human sera is related to numbers of previous
      spontaneous abortions and nutritional factors.
AB  - OBJECTIVES: The objectives were to determine (1) if sera from women with
      histories of spontaneous abortions were teratogenic to cultured embryos more
      often than were sera of nonaborters, (2) if the teratogenicity could be corrected
      by adding nutrients to the sera, and (3) if these findings were relevant to
      reproductive outcomes. STUDY DESIGN: Rat embryos were cultured for 48 hours on
      sera from 102 subjects who had experienced spontaneous abortions. Samples from 48
      were retested with nutrients added and 10 took dietary supplements, were again
      tested with embryo cultures, and reported on their pregnancy outcomes. RESULTS:
      The frequencies of teratogenic sera increased with numbers of spontaneous
      abortions (0 to > or = 5) in a manner that did not deviate from linearity (27% to
      89%) (chi 2 p > 0.957). Nutrient supplements were added to 48 samples, and 40
      were corrected and 10 subjects were given dietary supplement. Sera from six
      showed improved embryo cultures, and these women completed their pregnancies.
      CONCLUSIONS: Rat embryo cultures may provide unique insights into the causes and
      treatment of spontaneous abortions.

PMID- 8296828
TI  - Gestational changes in endothelium-dependent vasorelaxation in human umbilical
      artery.
AB  - OBJECTIVE: We intended to clarify whether (1) the amount of endothelium-derived
      vasorelaxing factor or nitric oxide released by histamine is sufficient to cause
      relaxation in human umbilical artery at different stages of gestation and (2) the
      functional role of endothelium-derived relaxing factor changes with the progress
      of gestation. STUDY DESIGN: By means of a bioassay cascade technique with very
      thin muscle strips, which allows rapid diffusional access of applied drugs (of
      the order of a few seconds), contractile properties were examined. RESULTS: At 18
      to 22 weeks of gestation histamine produced only a minor contraction, but as
      gestation progressed the contractile responses increased. L-NG-nitro-arginine
      greatly enhanced the histamine-induced contractions. Histamine produced a
      concentration-dependent relaxation during the maintained contraction induced by
      39 mmol/L K+ in tissues from 18 to 22 weeks or 30 to 32 weeks but not 38 to 41
      weeks of gestation. Thus the concentration-relaxation relationship for histamine
      showed decreased sensitivity during gestation. The histamine-induced relaxation
      was enhanced by superoxide dismutase and completely blocked by L-NG-nitro
      arginine or mepyramine (H1 antagonist). The concentration-relaxation relationship
      for the action of glycerol trinitrate relaxation decreased as gestation
      progressed. In a bioassay cascade an endothelium-intact umbilical artery from 18
      to 22 or 38 to 41 weeks of gestation was used as a "donor" and L-NG-nitro
      arginine-treated umbilical artery from 18 to 22 and 38 to 41 weeks as a
      "detector." In the presence of histamine the perfusate that had passed through a
      donor from 18 to 22 weeks (but not 38 to 41 weeks) attenuated the high K(+)
      induced contraction in the detector only from 18 to 22 weeks. CONCLUSION: These
      results suggest that the amount of endothelium-derived relaxing factor and the
      sensitivity of smooth muscle to endothelium-derived relaxing factor decreased
      with the progress of gestation.

PMID- 8296829
TI  - The p53 tumor suppressor gene frequently is altered in gynecologic cancers.
AB  - Mutation of the p53 tumor suppressor gene, often accompanied by overexpression of
      mutant p53 protein, is the most frequent molecular genetic event described thus
      far in human cancers. In adenocarcinomas of the ovary and endometrium, p53
      overexpression is seen in approximately 10% to 15% of early and 40% to 50% of
      advanced cancers. Similar to many other types of human cancers, ovarian and
      endometrial cancers that overexpress p53 protein contain mutations in conserved
      regions of the p53 gene. These mutations are predominantly transitions, which
      suggests that they arise spontaneously rather than being caused by carcinogen
      exposure. Alteration of the p53 gene does not appear to be a feature of
      endometrial hyperplasias or benign or borderline ovarian tumors. Although
      mutation and overexpression of p53 rarely occur in cancers of the cervix, vulva,
      and vagina, it has been shown that human papillomavirus E6 oncoproteins bind to
      and inactivate p53 protein. Studies of the p53 gene have begun to provide insight
      into the molecular pathogenesis of gynecologic cancers.

PMID- 8296830
TI  - Transient blood oxygen desaturation, hypercapnia, and coagulopathy after
      operative hysteroscopy with glycine used as the distending medium.
AB  - OBJECTIVE: Our purpose was to report transient complications associated with
      operative hysteroscopy with glycine used as the distending medium. STUDY DESIGN:
      All the operative hysteroscopies performed over a 6-month period by a single
      operator were examined. The blood oxygenation and end-tidal carbon dioxide
      concentrations were monitored in all cases with a pulse oximeter and a
      capnograph. Blood samples were obtained during the operation and over the next
      day to determine coagulation functions, sodium levels, and a complete blood cell
      count. RESULTS: Oxygen desaturation accompanied by a simultaneous increase in
      blood carbon dioxide levels occurred in six of the 46 patients. In addition, four
      of these patients were found to have a significant blood coagulopathy.
      Hyponatremia was observed in only two of the latter patients. CONCLUSION:
      Patients undergoing transcervical resection of the endometrium or submucous
      myomectomy must be closely monitored because disturbances in oxygenation and
      coagulation functions are not rare. The possibility of avoiding these
      complications by careful control of intrauterine pressure and the absorption of
      glycine should be further examined.

PMID- 8296831
TI  - Is there still a need for laparotomy in case of postmenopausal adnexal tumors?

PMID- 8296832
TI  - Why not begin "active management" of prolonged pregnancy sooner?

PMID- 8296833
TI  - Laparoscopic pelvic surgery: better? Safer?

PMID- 8296834
TI  - Is laparoscopic treatment of endometriosis better?

PMID- 8296835
TI  - Prevention of meconium aspiration syndrome.

PMID- 8296836
TI  - Definition of pelvic abscess.

PMID- 8296837
TI  - Does maternal diabetes delay fetal pulmonary maturity?

PMID- 8296838
TI  - Uterine size as indication for early hysterectomy.

PMID- 8296839
TI  - The umbilical coiling index.
AB  - OBJECTIVE: Our purpose was to objectively quantitate umbilical vascular coiling.
      STUDY DESIGN: In this prospective study the umbilical cords and delivery records
      of 100 consecutive liveborn neonates were studied. The umbilical coiling index of
      each cord was determined by dividing the total number of complete umbilical
      vascular coils by the umbilical cord length (in centimeters). The obstetric
      history, intrapartum fetal heart rate tracing, and pregnancy outcome of each
      fetus were evaluated without knowledge of the umbilical coiling index. RESULTS:
      The mean umbilical coiling index was 0.21 +/- 0.07 (SD) coils per centimeter. The
      100 values were normally distributed. Among those whose umbilical coiling index
      values fell < or = 10th percentile, there was a significantly greater incidence
      of karyotypic abnormalities (p = 0.04), meconium staining (p = 0.03), and
      operative intervention for fetal distress (p = 0.03). There was a significantly
      greater incidence of moderate or severe variable fetal heart rate decelerations
      for those whose umbilical coiling index value was either < or = 10th percentile
      (0.1 coils per centimeter) or > 90th percentile (0.3 coils per centimeter) (p =
      0.03). CONCLUSION: The umbilical coiling index may have utility for objectively
      describing the degree of umbilical vascular coiling.

PMID- 8296840
TI  - A three-year follow-up of children imaged in utero with echo-planar magnetic
      resonance.
AB  - A 3-year follow-up study was carried out on 20 children examined in utero with
      echo-planar magnetic resonance imaging when fetal compromise had been
      demonstrated or was suspected. There was no demonstrable increase in the
      occurrence of disease or disability (including hearing deficit) that could be
      related to echo-planar imaging techniques.

PMID- 8296841
TI  - Pregnancy and birth rates of live infants after in vitro fertilization in women
      with an without previous in vitro fertilization pregnancies: a study of eight
      thousand cycles at one center.
AB  - OBJECTIVE: Our aim was to compare the cumulative conception and live-birth rates
      after in vitro fertilization in women undergoing their first course of in vitro
      fertilization treatment with those in women undergoing their second course of
      treatment, having previously achieved an in vitro fertilization pregnancy. This
      study occurred in a tertiary referral-assisted conception unit. STUDY DESIGN: The
      cumulative conception rates obtained by life-table analysis in 4115 women having
      their first course of in vitro fertilization therapy (7327 treatment cycles
      leading to 1123 pregnancies) were compared by means of the log-rank test with
      those of 331 women in their second course of treatment, having previously
      achieved an in vitro fertilization pregnancy (561 treatment cycles leading to 138
      second in vitro fertilization pregnancies). Similarly, the cumulative live birth
      rates of 3824 women in their first course of treatment (7136 treatment cycles
      leading to 732 live births) were compared with those of 105 women in their second
      course of treatment, having previously achieved an in vitro fertilization live
      birth (205 treatment cycles leading to 33 second in vitro fertilization live
      births). RESULTS: The cumulative conception rates and cumulative live birth rates
      were significantly higher in women having their second course of in vitro
      fertilization treatment than in those having their first course (cumulative
      conception rate: p = 0.0001; cumulative live birth rate, p = 0.007). After five
      cycles of in vitro fertilization, the cumulative conception rates and cumulative
      live birth rates were 49.8% (95% confidence interval, 46.3% to 53.5%) and 39.0%
      (95% confidence interval, 35.4% to 42.9%), respectively, in those having their
      first course of treatment compared with 69.9% (95% confidence interval, 57.6% to
      81.3%) and 68.6% (95% confidence interval, 46.1% to 88.5%), respectively, in
      those having their second course. The estimated median numbers of cycles taken to
      achieve a pregnancy and live birth (assuming all women could potentially undergo
      the same number of cycles) were six and eight, respectively, in the first course
      of treatment compared with only three and five in the second course. CONCLUSION:
      Women who have achieved a previous in vitro fertilization pregnancy have
      significantly higher cumulative conception rate and cumulative live birth rates
      compared with those of women having their first course of treatment.

PMID- 8296842
TI  - Differences between black and white women in the use of prenatal care
      technologies.
AB  - OBJECTIVE: The purpose of this study was to determine whether the content of
      prenatal care received by black and white women in the United States differs, as
      measured by the use of amniocentesis, ultrasonography, and tocolysis. STUDY
      DESIGN: This study uses data from birth certificates issued for births occurring
      in the United States in 1990. Multivariate analyses were used to calculate the
      relative risk of receipt of each technology by black women compared with white
      women. RESULTS: Amniocentesis was used substantially less frequently by black
      women (relative risk 0.6), whereas ultrasonography was received by black women
      slightly less frequently than white women (relative risk 0.9). Tocolysis used
      varied by plurality. Black women with singleton births were slightly more likely
      to receive tocolysis than were white women (relative risk 1.1), although the risk
      of idiopathic preterm delivery is estimated to be three times higher in black
      women. Black women with multiple births received tocolysis two thirds as often as
      white women. CONCLUSIONS: These results suggest that differences exist in the
      content of prenatal care received by black and white women in the United States.
      This finding should be followed up with more detailed studies to identify its
      cause and possible interventions.

PMID- 8296843
TI  - Urinary tract injuries during laparoscopically assisted hysterectomy: causes and
      prevention.
AB  - Two patients who had urinary fistulas after laparoscopic hysterectomy are
      described. In both cases the ureters were dissected free and the uterus was freed
      laparoscopically. Injury to the urinary tract occurred during transvaginal
      closure of the vaginal cuff. Preventative strategies are discussed.

PMID- 8296844
TI  - Acid-base status at birth and subsequent neurosensory impairment in surviving 500
      to 1000 gm infants.
AB  - OBJECTIVE: The purpose of this study was to assess, in infants born weighing < or
      = 1000 gm, if umbilical cord blood acid-base measures at birth are associated
      with an additional increase in neurosensory impairment. STUDY DESIGN: Of 289
      surviving infants with a birth weight of 500 to 1000 gm born from 1979 to 1989,
      219 had umbilical cord acid-base status measured at birth and were followed
      prospectively for > or = 1 year. Measures of neurologic impairment used in this
      study included mental retardation, cerebral palsy, and major neurosensory
      impairment. RESULTS: Gestational age was inversely associated with all
      neurosensory impairments and was a better predictor of subsequent impairment in
      this population than was birth weight. Very low umbilical cord pH values were
      also significantly related to adverse outcomes. There was also an inverse
      relationship between cord blood bicarbonate levels and major neurosensory
      impairment. The highly significant relationship between cord blood bicarbonate
      and pH values and the development of neurosensory impairments persisted in spite
      of adjustment for gestational age, birth weight, plurality, use of general
      anesthesia, maternal race, and presence of hypertension. CONCLUSION: An adverse
      acid-base status at birth is additive to the effect of gestational age in
      predicting neurosensory impairment in infants weighing < or = 1000 gm.

PMID- 8296845
TI  - The West Los Angeles Preterm Birth Prevention Project. I. Program impact on high
      risk women.
AB  - OBJECTIVE: The primary objective of this prospective study was to test whether
      preterm birth prevention education plus increased clinic visits and selected
      prophylactic interventions reduce preterm birth. STUDY DESIGN: Eight West Los
      Angeles prenatal county clinics, comparable with respect to selected
      demographics, were randomized to be either experimental or control clinics. High
      risk patients in all clinics were identified with a risk scoring system derived
      from a similar population. High-risk patients (N = 1774) in experimental clinics
      were offered a program of education and more frequent visits and were randomized
      to receive various secondary intervention protocols in addition to the basic
      interventions of education and more frequent visits. Control clinic patients (N =
      880) received standard county care. RESULTS: Preterm birth rates were 19% lower
      among the experimental high-risk patients (7.4% vs 9.1%), and differences were
      significant (p < 0.05) when preterm risk was taken into account. There was no
      evidence to suggest that the secondary interventions provided added benefit over
      the primary intervention protocol of preterm birth prevention education and
      increased visits. CONCLUSION: The 19% reduction in preterm birth rate observed in
      the experimental clinics suggest an overall program benefit from a protocol that
      offered education, more frequent visits, and greater attention given to patients
      while the selected interventions were applied.

PMID- 8296846
TI  - Sharing of human leukocyte antigens in couples with unexplained infertility
      affects the success of in vitro fertilization and tubal embryo transfer.
AB  - OBJECTIVE: The purpose was to test further our hypothesis that genes, or genetic
      defects, linked to the major histocompatibility complex affect reproduction by
      correlating human leukocyte antigen sharing with the success or failure of in
      vitro fertilization and tubal embryo transfer in couples having unexplained
      infertility. STUDY DESIGN: Seventy-six couples with unexplained infertility who
      failed superovulation and intrauterine insemination at least three times were
      typed for human leukocyte antigens and treated by in vitro fertilization and
      tubal embryo transfer. The results were correlated with the sharing of human
      leukocyte antigens in the couples. RESULTS: Thirty-four of the women had
      successful pregnancies, 36 did not become pregnant, and six became pregnant but
      aborted shortly thereafter. There was a highly significant excess of human
      leukocyte antigen sharing in the couples who failed treatment: three of the A, B,
      DR, and DQ antigens (p = 0.015) or two of the B, DR, and DQ antigens (p = 0.015).
      No specific human leukocyte antigen alleles were present in excess. CONCLUSIONS:
      Genes, or genetic defects, linked to the major histocompatibility complex
      significantly affect the success of in vitro fertilization and tubal embryo
      transfer just as they affect the prevalence of recurrent spontaneous abortion,
      cancer, and congenital anomalies. It appears as if the critical genes, or genetic
      defects, are located in the B-DR-DQ region of the major histocompatibility
      complex.

PMID- 8296847
TI  - The history and future of operative laparoscopy.
AB  - Laparoscopic sterilization was first performed in the United States in 1941.
      During the 1950s and 1960s hospitals procured the relatively inexpensive basic
      laparoscopic instrumentation, and education for physicians learning the
      techniques was provided mostly by academic centers during residency training.
      Interest in expansion of laparoscopic procedures was slight until the mid-1980s
      when operative laparoscopic management of ectopic pregnancies began to spread
      from academic centers to the private sector. Major technologic developments in
      instrumentation greatly simplified the endoscopic procedures and provided the
      first impetus for an explosive growth of operative laparoscopic applications in
      surgery. The great financial resources of private hospitals enabled them to adapt
      and retool quickly for operative endoscopy. Lacking these resources, academic
      institutions lagged behind; thus a growing divergence began between academic and
      private institutions in their influence on the development, use, and acceptance
      of the new technology. The development of expensive disposable instruments, with
      costs passed on to patients by private hospitals, further priced academic
      institutions out of the market. Two concerns today are paramount regarding
      operative laparoscopy: (1) The majority of laparoscopic techniques and procedures
      being performed by surgeons in this country have not been taught in the
      controlled setting of a residency or fellowship training program; (2) the
      legitimacy of the procedures themselves is questionable because of lack of
      sufficient data in the literature to support them. Academic institutions, working
      in tandem with the private sector, must assume the responsibility for answering
      these concerns.

PMID- 8296848
TI  - Lamellar body concentrations and the prediction of fetal pulmonary maturity.
AB  - OBJECTIVE: Amniotic fluid lamellar body concentration was quantified in pregnancy
      and compared with the lecithin/sphingomyelin ratio and phosphatidylglyceryl to
      predict fetal lung maturity. STUDY DESIGN: Amniotic fluid was obtained from 56
      patients at various gestational ages (16 to 42 weeks) and quantified on a Coulter
      counter set for particle size used for platelets (2 to 20 fl). The lamellar body
      concentration best agreeing with a mature lecithin/sphingomyelin ratio of 2 and
      with phosphatidylglycerol was determined. The lamellar body concentration cutoff
      was compared with the lecithin/sphingomyelin ratio and phosphatidylglycerol as a
      predicator of fetal lung maturity. RESULTS: Lamellar body concentration increased
      exponentially with gestation (r = 0.70, p < 0.001), as did the
      lecithin/sphingomyelin ratio (r = 0.78, p < 0.001). The two tests correlated with
      each other linearly (r = 0.67, p < 0.001). The lamellar body concentration cutoff
      value that best agreed with both mature lecithin/sphingomyelin ratio and
      phosphatidylglycerol was 30,000/microliters (kappa-test 0.66 and 0.73,
      respectively). In 28 patients delivered within 72 hours the lamellar body
      concentration correctly predicted four cases of respiratory distress syndrome
      (100% sensitivity and specificity). CONCLUSION: This study confirms that lamellar
      body concentration is a reliable and practical assay and should be evaluated
      further, especially for use in a community hospital setting.

PMID- 8296849
TI  - Transvaginal ultrasonographic characterization of ovarian masses with an
      improved, weighted scoring system.
AB  - OBJECTIVE: The aim of the study was to modify a previously devised morphologic
      scoring system with the use of transvaginal ultrasonography in the hope of
      improving discrimination of benign from malignant ovarian and adnexal masses.
      STUDY DESIGN: Transvaginal ultrasonographic images of 312 patients for a total of
      350 ovarian and adnexal masses were obtained over a 3-year period. The derived
      morphologic data were analyzed by multiple linear regression analysis to select
      the best performance of the previously described scoring system by Sassone et al.
      in 1991. This system was thus modified in several ways including weighted point
      value assignments, fewer point values per variable studied, the deletion of one
      variable found not to be significant (wall thickness), and the inclusion of a new
      variable called shadowing. RESULTS: At surgery, 308 benign masses, 31 malignant
      masses, and 11 tumors of low malignant potential were found. The mean point value
      obtained was 1.8 for the benign masses, 3.9 for the tumors of low malignant
      potential, and 5.6 for the malignant tumors (p < 0.0005). With a cutoff of > or =
      3 used as the best discriminator, the sensitivity was 96.8% and the specificity
      77%. The positive and negative predictive values were 29.4% and 99.6%,
      respectively. CONCLUSION: Limitations of the previously devised scoring system
      included the arbitrary point assignments of each variable, the multiple (4 or 5)
      point choices for each variable, and the poor positive predictive value. This new
      scoring system performs well in the differentiation of benign from malignant
      masses, while assigning scientifically derived, therefore more valid, point
      values and simplifying the system overall. That the positive predictive value was
      not improved proves that ultrasonographically, to date we are still hampered by
      complex and malignant-appearing benign ovarian masses.

PMID- 8296850
TI  - Antenatal vitamin K therapy of the low-birth-weight infant.
AB  - OBJECTIVE: The purpose of our study was to determine whether maternal vitamin K1
      administered antenatally improved global coagulation parameters and the levels of
      specific vitamin K-dependent proteins in low-birth-weight infants. STUDY DESIGN:
      Thirty-three preterm mothers admitted in labor were assigned in a prospective,
      blinded fashion to receive either intramuscular vitamin K1 (17) or placebo (16).
      At delivery cord blood samples were tested for prothrombin time, activated
      partial thromboplastin time, factor II and protein C activity, and antigen
      levels. Statistical analysis was by Student t test. RESULTS: No statistically
      significant differences could be demonstrated with regard to group mean values
      for global tests (prothrombin time, activated partial thromboplastin time) or
      specific vitamin K-dependent protein levels (factor II, protein C) in newborns
      whose mothers received antenatal vitamin K compared with those who did not.
      CONCLUSION: These results would suggest that antenatal vitamin K1 therapy to
      mothers < 32 weeks' gestation has no significant effect on the level of vitamin K
      dependent factors in the fetus.

PMID- 8296851
TI  - A comparison of propylthiouracil versus methimazole in the treatment of
      hyperthyroidism in pregnancy.
AB  - OBJECTIVE: Our purpose was to demonstrate that propylthiouracil and methimazole
      are equally effective and safe in the treatment of hyperthyroidism during
      pregnancy. STUDY DESIGN: Between 1974 and 1990 records were available on 185
      pregnant patients with a history or diagnosis of hyperthyroidism. Ninety-nine
      patients were treated with propylthiouracil and 36 with methimazole. The response
      to therapy was compared with respect to the time to normalization of the free
      thyroxine index and the incidences of congenital anomalies and hypothyroidism.
      RESULTS: The time to normalization of the free thyroxine index was compared in
      the two groups by means of survival analysis. The median time to normalization of
      the free thyroxine index on propylthiouracil and methimazole was 7 and 8 weeks,
      respectively (p = 0.34, log-rank test). The incidence of major congenital
      malformations in mothers treated with propylthiouracil and methimazole was 3.0%
      and 2.7%, respectively. No neonatal scalp defects were seen. One infant was
      overtly hypothyroid at delivery. CONCLUSION: Propylthiouracil and methimazole are
      equally effective and safe in the treatment of hyperthyroidism in pregnancy.

PMID- 8296852
TI  - Direct growth inhibition of human endometrial cancer cells by the gonadotropin
      releasing hormone antagonist SB-75: role of apoptosis.
AB  - OBJECTIVE: Our objective was to study the direct action of the gonadotropin
      releasing hormone antagonist SB-75 and the agonist buserelin on the proliferation
      of endometrial cancer cells. STUDY DESIGN: Two human endometrial cell lines that
      differ in histologic subtype and estrogen receptor content were treated with
      gonadotropin-releasing hormone analog. We measured the number of viable cells,
      cell cycle parameters, and apoptotic processes. RESULTS: Growth of the Ishikawa
      cells was inhibited by SB-75 in a dose-dependent manner. 17 beta-Estradiol
      partially abolished the inhibitory effect of SB-75. The growth of the HEC-1A
      cells was not affected by the antagonist. Neither endometrial cancer cell line
      showed significant sensitivity to the agonist buserelin. Tenfold concentration of
      the gonadotropin-releasing hormone agonist did not abolish the inhibitory effect
      of the antagonist on cell growth. The growth inhibition was not associated with
      any change in cell cycle parameters but was associated with an induction of
      apoptosis. CONCLUSION: The gonadotropin-releasing hormone antagonist SB-75
      directly inhibits the growth of some human endometrial cancer cells and thus may
      be suitable for the treatment of endometrial tumors.

PMID- 8296853
TI  - Intraoperative facial nerve monitoring in acoustic neuroma surgery.
AB  - Intraoperative facial nerve monitoring simultaneously using electromyography and
      mechanical pressure sensors is being used in retrosigmoid and translabyrinthine
      approaches for acoustic neuroma resection. Insulated electrified microsurgical
      instruments and air drills are used to stimulate the facial nerve with a pulsed,
      constant current through bone and tumor, before the facial nerve is visually
      encountered. Electrical stimulation is used to help locate the facial nerve, map
      the course of the facial nerve within tumor, warn the surgeon of unexpected
      facial nerve locations, and help predict facial nerve function postoperatively.
      In 57 unmonitored cases a House-Brackmann (H-B) grade I or II result was obtained
      in 77 percent of small, 81 percent of medium, and 60 percent of large tumors. In
      64 monitored cases H-B grade I or II was obtained in 88 percent of small, 79
      percent of medium, and 90 percent of large tumors. Overall, facial nerve outcomes
      were better after monitored procedures (p < 0.02). A modified H-B classification
      for acute facial nerve injury is introduced to grade facial weakness immediately
      postoperatively and until function is stable at 1 year. In the unmonitored group
      there were five (9%) cases with a complete facial paralysis, facial nerve intact
      (i.e., acute H-B grade VIA) and seven (13%) cases with the facial nerve
      transected (i.e., acute H-B grade VIB). In the monitored group there were five
      (8%) acute H-B grade VIA and two (3%) acute H-B grade VIB results. In the
      unmonitored group of large tumors, there were statistically more patients with an
      acute H-B grade VIB result (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8296854
TI  - Translabyrinthine approach to skull base tumors with hearing preservation.
AB  - The improvement in surgical techniques and the experience gained in treatment of
      skull base tumors have stimulated more aggressive management of larger lesions.
      Patients presenting with limited preoperative deficits have challenged the
      surgeon to design the surgical approach so as to minimize postoperative morbidity
      and preserve function. Tumors of the middle fossa and clivus with extension into
      the posterior fossa are usually approached by a combined subtemporal,
      transtentorial, transpetrous approach. In patients with preoperative hearing, the
      surgical exposure is often limited by the labyrinthine portion of the otic
      capsule. The technique of partial labyrinthectomy, removing the posterior and/or
      superior semicircular canals, maximizes exposure with preservation of hearing.
      This report details our experience with the partial labyrinthectomy approach for
      14 patients with large skull base lesions. All patients had hearing preserved
      despite sacrifice of one or two of the semicircular canals. Bone pure-tone
      averages and speech discrimination scores were maintained near their preoperative
      levels. The indications, benefits, techniques, and hearing results of this
      approach are reviewed.

PMID- 8296855
TI  - Neurotologic presentation of sagittal sinus thromboses associated with oral
      contraceptive usage.
AB  - Thrombosis of the cerebral venous sinuses has long been a recognized complication
      of late stage pregnancy and the puerperium; more recently, this complication has
      been associated with the use of oral contraceptives. Two cases are presented in
      which the presenting symptoms of sagittal sinus thrombosis were neurotologic in
      nature. One case presented with a sudden onset unilateral facial paralysis;
      another case presented with pressure/fullness sensation in one ear accompanied by
      nausea and vomiting. Clinical presentation and evaluation of these cases is
      presented, with a discussion of symptom etiology. Recommended non-invasive
      medical management methods are discussed. Cases in which the thrombosis involves
      the sigmoid, transverse, and sagittal sinuses should be suspect for etiologic
      sources beyond the ear even when the presenting symptoms are neurotologic in
      nature. Management of these cases is different from that of an otogenic sigmoid
      sinus thrombosis. A complete medical history taken from women of child bearing
      age should include the use of oral contraceptives, which may be suspect for
      inducing intracranial venous thromboses.

PMID- 8296856
TI  - Dural defects of the temporal bone.
AB  - Cerebrospinal fluid leakage (otorrhea or otorhinorrhea) from the temporal bone is
      the end result of rupture of the arachnoid membrane or herniation of the brain
      through a defect in the protective dura mater and calvarium. The rupture may be
      small, admitting only a herniation of arachnoid (meningocele), or be large enough
      to accommodate brain tissue (encephalocele). Flow of cerebrospinal fluid through
      either type of fistula may be a trickle or profuse, chronic or intermittent, and
      usually ceases temporarily for a few weeks following an attack of meningitis. The
      etiology, anatomy, signs and symptoms, and various methods of treatment for
      cerebrospinal fluid otorrhea and otorhinorrhea are discussed.

PMID- 8296857
TI  - Headache after acoustic neuroma excision.
AB  - The retrosigmoid approach to acoustic neuroma removal has recently been
      criticized for causing frequent and severe headache postoperatively. We review
      331 patients who had acoustic neuroma removal by the retrosigmoid approach at one
      institution. The incidence of postoperative headache was 23 percent at 3 months,
      16 percent at 1 year, and 9 percent at 2 years. Management was primarily with
      analgesics, physiotherapy, and reassurance. No patient had additional surgical
      treatment. Information available indicates that the incidence of postoperative
      headache associated with the translabyrinthine approach is similar to that of the
      retrosigmoid approach. Perhaps filling the craniectomy defect will decrease
      further the incidence of headache postoperatively.

PMID- 8296858
TI  - Delayed perception of cochlear implant stimulation in children with
      postmeningitic ossified cochleae.
AB  - A possible complication of postmeningitic deafness is cochlear ossification.
      Reports of immediate response to electrical stimulation despite this ossification
      have been encouraging. This report discusses three children who initially failed
      to perceive stimulation from their Nucleus multichannel cochlear implants. These
      patients showed no behavioral responses to any of 10 to 20 electrodes inserted
      into their ossified cochleae, even at maximum stimulus levels (1750 microA).
      Stimulus-response behavior had been well documented prior to implantation and was
      not considered a factor in their failure to respond. These patients continued to
      wear the speech processors programmed at maximum stimulus/current levels.
      Eventually, all three patients began responding following 5 to 12 months of
      device use. These results suggest that continued use of electrical stimulation
      may result in eventual perception.

PMID- 8296859
TI  - Hearing preservation in bilateral acoustic neuroma surgery.
AB  - Patients with neurofibromatosis type 2 (NF2) develop bilateral acoustic neuromas,
      but preservation of hearing while achieving tumor removal may present several
      unique problems. Our philosophy regarding hearing preservation attempts in these
      cases has evolved over several decades. The outcome of hearing preservation
      surgery using the middle cranial fossa approach for 13 procedures in 10 patients
      with NF2 is presented. There were 12 total tumor removals and one partial tumor
      removal. Two ears retained good postoperative hearing, three had serviceable
      hearing, four had measurable hearing, and four had no measurable hearing. Both
      cases with tumors 2 cm or larger retained no hearing. For the 12 total tumor
      removals, the rate of hearing preservation was 67 percent. Of four total removals
      with long-term follow-up, two retained good or serviceable hearing. The rate of
      hearing preservation is similar to that found in our series of unilateral
      acoustic neuroma surgeries. Based on these findings, hearing preservation surgery
      is recommended for patients with NF2 who have acoustic neuromas 1.5 cm or
      smaller.

PMID- 8296860
TI  - Clinical assessment of postural stability.
AB  - It is important to evaluate both vestibulo-oculomotor and vestibulospinal
      pathways in patients with balance disorders. While moving-platform posturography
      can assess vestibulospinal function, the cost and time required to perform this
      test may limit its clinical use. A clinical office vestibulospinal evaluation
      that could be done quickly and inexpensively would be of benefit. In this study
      we used foam posturography to prospectively evaluate 50 patients with vestibular
      complaints to determine its predictive value in comparison with moving-platform
      posturography results. Our results demonstrate a significant correlation (p <
      0.005) with a sensitivity and specificity of 95 percent and 90 percent,
      respectively, between the clinical office assessment using foam posturography and
      the results of moving-platform posturography. The ability of patients to utilize
      vestibular cues to maintain posture may be accurately assessed in a clinical
      office examination and should be useful to otolaryngologists to evaluate the
      vestibulospinal system.

PMID- 8296861
TI  - Factors influencing results with streptomycin perfusion of the labyrinth.
AB  - Streptomycin perfusion of the labyrinth is the logical choice of treatment for
      the third stage of Meniere's disease with intractable vertigo. The results of
      streptomycin perfusion of the labyrinth are comparable to those of other
      treatments, including endolymphatic shunt and vestibular nerve section.
      Refinements must be made in the process of selecting candidates for the
      operation. To study the factors influencing the results of streptomycin perfusion
      of the labyrinth, 144 patients who had streptomycin perfusion of the labyrinth
      and were followed for 1 year were studied using the 1972 AAOO classification of
      results. The findings of this study indicate that only a low dosage of
      streptomycin and a small volume of perfusate are required to obtain good results.
      Patients who have long lasting severe endolymphatic hydrops with poor hearing
      preoperatively are less likely to achieve good results.

PMID- 8296862
TI  - Surgical anatomy of the endolymphatic sac.
AB  - At present several different surgical modalities are available to the surgeon who
      is about to relieve dizzy patients of their vertigo. Although the majority of
      these procedures belong to the destructive category, endolymphatic sac-mastoid
      shunting is a relatively harmless and nondestructive procedure. The success of
      such an operation is, however, dependent on the fact that the surgeon really
      identifies and penetrates the endolymphatic sac lumen. This is probably not
      always the case, and the present article describes the large variability seen in
      the surgical anatomy of the endolymphatic sac. In some cases there is no
      extratemporal extension of the sac at all, which, of course, makes it impossible
      to identify and penetrate the sac. The large variability among individual cases
      is described and discussed.

PMID- 8296863
TI  - Manometric and endoscopic study of tubal function in drum perforation.
AB  - Since good ventilation of the middle ear is a prerequisite to successful
      myringoplasty, it was our policy to study the tubal function in dry central
      perforation of the drum and to correlate the manometric with the endoscopic
      findings. Normal manometric results with patency of the tube (as proved by
      fluorescein-endoscopy) indicated good tubal function, with good prognosis for
      myringoplasty. Abnormal manometric results with failure of fluorescein to pass
      into the nasopharynx indicated mechanical tubal obstruction that was, in most
      cases, correctable. Nasal endoscopy proved to be indispensable in diagnosing,
      localizing, and even treating "hidden" lesions in their key areas that may be
      responsible for the obstruction. Thus, the correction of the mechanical tubal
      obstruction must precede ear surgery. Whenever tubal obstruction is diagnosed as
      functional or idiopathic, the ventilation of the middle ear should be facilitated
      during ear surgery by addition of a tympanostomy tube to the graft or drum
      remnant, with guarded prognosis.

PMID- 8296864
TI  - Surgical management of CSF otorhinorrhea following retrosigmoid removal of
      cerebellopontine angle tumors.
AB  - Cerebrospinal fluid (CSF) otorhinorrhea continues to be one of the most common
      complications following surgery for cerebellopontine angle (CPA) tumors. For
      retrosigmoid approaches, this complication has been reported to occur in 12-19
      percent of patients. Nearly all prior surgical attempts at control have included
      middle ear and eustachian tube obliteration along with packing of the mastoid.
      This article reviews 165 retrosigmoid procedures (January 1982-December 1990) for
      removal of CPA tumors, with a leak rate of 9.8 percent (16 cases), 7.2 percent
      (12 cases) requiring surgical control. An operative technique involving only
      mastoid obliteration is presented. This approach is less invasive as it limits
      the scope of the surgical field and also maintains the integrity of the middle
      ear for potential preservation of hearing. This approach has resulted in control
      in 100 percent of the patients, without reoperation. The routes of the CSF leak,
      the technique, and the rationale for its use are presented.

PMID- 8296865
TI  - Prevention of recurrence of cholesteatoma in intact canal wall tympanoplasty.
AB  - In the treatment of cholesteatoma employing intact canal wall tympanoplasty,
      staging the operation and re-establishment of aeration of the tympanic cavity are
      required to eradicate possible causes of recurrence, cholesteatoma residue, and
      retraction pocket. The planned staged tympanoplasty with preventive measures for
      recurrence has evolved. At the second-stage operation, one of the following three
      types of operations was performed according to the grade of aeration and healing
      of tympanic cavity: type S1, only ossiculoplasty; type S2, ossiculoplasty and
      scutumplasty; and type S3, ossiculoplasty, scutumplasty, and mastoid
      obliteration. The surgical concept, indication, and technique are described in
      detail. The recurrence rate in the 134 patients without previous surgery, 95
      adults and 39 children, operated on between 1987 and 1991 was 2.2 percent (7.6%
      in the children and 0% in the adult). Although the rate of the recidivism was
      significantly reduced, deep retraction pocket developed in 15 percent of adults
      and in 23 percent of children. The incidence of deep retraction pocket formation
      was lowest in the adults with type S1 operation and highest in the children with
      type S3 operation.

PMID- 8296866
TI  - Effect of handedness on the middle latency auditory evoked potential.
AB  - The effect of handedness on the middle latency response of the auditory evoked
      potential was investigated by testing 16 right-handed and 16 left-handed young
      adults with normal hearing. Each handedness group contained eight males and eight
      females. Peaks PO, N(a),P(a),Nb,and Pb showed a progressive, statistically
      significant latency increase in left-handed subjects when compared with right
      handed subjects. The latency difference was 1.1 ms at peak P(a) and 3.6 ms at
      peak Pb. There was no significant latency difference between males and females.
      Topographic brain mapping showed that the distribution of positivity of wave Pb
      was similar to the distribution for wave P(a) in both right- and left-handed
      subjects.

PMID- 8296867
TI  - Role of magnetic resonance imaging in the diagnosis of bilateral facial
      paralysis.
AB  - Bilateral facial paralysis (BFP) is a rare clinical finding that may be caused by
      Guillain-Barre syndrome, a medical emergency. The differential diagnosis of BFP
      is lengthy but can be narrowed to a limited group of disorders by the patient's
      history and physical examination. The most important diagnostic tests to obtain
      initially are the lumbar puncture and magnetic resonance imaging (MRI) scan with
      gadolinium contrast enhancement. Based on the MRI and lumbar puncture findings,
      additional tests may be appropriately ordered. The diagnosis of bilateral Bell's
      palsy is made by exclusion of other disorders. This report presents five cases of
      BFP (Guillain-Barre syndrome, herpes simplex polyneuritis, meningeal lymphoma,
      and two cases of bilateral Bell's palsy) in which MRI imaging helped in the
      diagnosis and subsequent management of the patient. The appropriate sequence of
      diagnostic studies for patients with BFP is discussed.

PMID- 8296868
TI  - Late partial recovery from meningitic deafness after cochlear implantation: a
      case study.
AB  - A child with well-documented total bilateral deafness as a result of meningitis
      contracted at the age of 2 years and 8 months demonstrated remarkably delayed
      recovery of hearing 14 months later. In the meantime cochlear implantation had
      been performed. Hearing returned partially in the nonimplanted ear and also in
      the ear implanted with a long multi-electrode intracochlear array, giving unaided
      thresholds at frequencies from 0.5 to 4 kHz of 60-80 dB and 90-105 dB,
      respectively. Despite this rare occurrence, it is concluded that a delay until 6
      months after meningitis before implantation is appropriate to detect most cases
      of spontaneous recovery of hearing.

PMID- 8296869
TI  - Impedance transfer: acoustic impedance of the annular ligament and stapedial
      tendon reconstruction in otosclerosis surgery.
AB  - The resistance rebuilt around the lower tip of the piston must be the same as
      that created by the annular ligament of the stapes footplate. Otherwise, the
      threshold at which an acoustic or barotrauma is able to damage the membranes and
      hair cells of the inner ear will be lowered. The elasticity reestablished around
      the lower tip of the piston plays a part in the quality and quantity of hearing
      for the low frequencies up to 3 kHz. To protect the ear against acoustic traumas,
      an attempt to rebuild the stapedial reflex is proposed.

PMID- 8296870
TI  - Temporal bone cancer.
AB  - Temporal bone cancer, a relatively rare disease, often presents in a subtle
      manner, which may delay diagnosis. It should be suspected in any case of
      persistent otitis media or otitis externa that fails to improve with adequate
      treatment. This article discusses physical and diagnostic imaging indications and
      epidemiology and histologic distribution of these tumors. Staging systems,
      patient selection criteria are presented as well as operative techniques and
      follow-up treatment. Despite advances in operative technique and postoperative
      care, long-term survival remains poor.

PMID- 8296871
TI  - Restoration of useful hearing following microvascular decompression of cochlear
      nerve.

PMID- 8296872
TI  - Taxonomic affinity of the early Homo cranium from Swartkrans, South Africa.
AB  - A quantitative analysis that employs randomization methods and distance
      statistics has been undertaken in an attempt to clarify the taxonomic affinities
      of the partial Homo cranium (SK 847) from Member 1 of the Swartkrans Formation.
      Although SK 847 has been argued to represent early H. erectus, exact
      randomization tests reveal that the magnitude of differences between it and two
      crania that have been attributed to that taxon (KNM-ER 3733 and KNM-WT 15000) is
      highly unlikely to be encountered in a modern human sample drawn from eastern and
      southern Africa. Some of the variables that differentiate SK 847 from the two
      early H. erectus crania (e.g., nasal breadth, frontal breadth, mastoid process
      size) have been considered to be relevant characters in the definition of that
      taxon. Just as the significant differences between SK 847 and the two early H.
      erectus crania make attribution of the Swartkrans specimen to that taxon
      unlikely, the linkage of SK 847 to KNM-ER 1813, and especially Stw 53, suggests
      that the Swartkrans cranium may have its closest affinity with H. habilis sensu
      lato. Differences from KNM-ER 1813, however, hint that the South African fossils
      may represent a species of early Homo that has not been sampled in the Plio
      Pleistocene of eastern Africa. The similarity of SK 847 and Stw 53 may support
      faunal evidence which suggests that Sterkfontein Member 5 and Swartkrans Member 1
      are of similar geochronological age.

PMID- 8296873
TI  - Fish-eaters and farmers: dental pathology in the Arabian Gulf.
AB  - Twelve skeletal samples, previously published, from the Arabian Gulf have been
      used to trace differences in diet and subsistence patterns through an analysis of
      dental pathology. The skeletons date from 3,000 BC to AD 1,500 and cover a
      variety of geographical locations: off-shore islands, Eastern Arabia, and Oman.
      The dental conditions analyzed are attrition, caries, calculus, abscessing, and
      antemortem tooth loss (AMTL). Results indicate four basic patterns of dental
      disease which, while not mutually exclusive, correspond to four basic subsistence
      patterns. Marine dependency, represented by the Ras el-Hamra population, is
      indicated by severe attrition, low caries rates, wear-caused abscessing, and a
      lack of AMTL. The second group of dental diseases--moderate attrition and
      calculus, low rates of caries, wear-caused abscessing, and low-moderate rates of
      AMTL--affects populations subsisting on a mixture of pastoralism or fishing and
      agriculture (Failaka, Umm an-Nar, Bronze Age Maysar, Bronze Age Shimal, and Iron
      Age Galilah). Mixed farming populations (Iron Age Maysar and Islamic Bahrain)
      experienced low-moderate attrition, high rates of caries and calculus, abscessing
      due to caries, and severe AMTL. The final group of dental diseases affects
      populations practicing intensive gardening (Bronze and Iron Age Bahrain, and
      Sites 3 and 5, Ras al-Khaimah). These groups experienced slight attrition, high
      rates of caries, low rates of calculus deposition, and severe AMTL.

PMID- 8296874
TI  - Reexamination of the immature hominid maxilla from Tangier, Morocco.
AB  - Reexamination of the immature Upper Pleistocene hominid maxilla from Mugharet el
      'Aliya (Tangier), Morocco is undertaken in light of new evidence on the growth
      and development of Upper Pleistocene hominids. Metric and qualitative comparisons
      were made with 17 immature Upper Pleistocene maxillae, and with a recent Homo
      sapiens sapiens sample. No unambiguous criteria for aligning the maxilla with
      Neandertals were found, although one character, the degree of maxillary flexion
      on the zygoma, strongly suggests that this child could be a representative of
      H.s. sapiens. The probable lack of a canine fossa in Mugharet el-'Aliya 1, the
      primary criterion used previously to align it with Neandertals, cannot be
      accurately extrapolated to its adult form from this juvenile. The present
      evidence suggests that it is inappropriate to refer to this fossil as "Neandertal
      like" or as a North African "neandertaloid." Thus, the Tangier maxilla should not
      be cited as evidence for the presence of Neandertal facial features in North
      Africa during the Upper Pleistocene.

PMID- 8296875
TI  - Ancient DNA from a pre-Columbian Amerindian population.
AB  - Ancient DNA was obtained from skeletal remains from the Norris Farms #36
      cemetery, a pre-Columbian archeological site in central Illinois that dates to
      A.D. 1300. Four mitochondrial DNA (mtDNA) markers were analyzed that delineate
      the four primary mtDNA lineages found in contemporary Amerindian populations.
      mtDNA types were determined for 50 individuals; 49 belonged to one of these four
      lineages. One lineage occurred only in males, suggesting an immigration of
      maternally related males into this community. There was no significant spatial
      patterning of mtDNA lineages within the cemetery. This survey of ancient DNA
      variation in a pre-Columbian population supports the view that the initial
      colonization of the New World comprised just four primary mtDNA lineages.

PMID- 8296876
TI  - Obesity in Pima Indians: large increases among post-World War II birth cohorts.
AB  - Several studies have shown secular increases in obesity during the past 35 years,
      and others have reported increases in dietary fat consumption during the same
      period. Here we report a dramatic increase in obesity among Pima Indians born
      after World War II that appears to be associated with increased exposure to
      Western customs and diet following 1945. We examined the body mass index (BMI =
      weight in kilograms/height2 in meters) of 1,128 male and 1,372 female Pima
      Indians aged 15-65 years who were born between 1901 and 1964 and were examined
      between 1965 and 1990. We found large increases in BMI among Pima Indian men and
      women in post-World War II birth cohorts (1945 and later). The parallel changes
      in body mass index, dietary fat, and exposure to Western culture following World
      War II suggest that culturally mediated changes in diet and level of physical
      activity associated with modern industrialized society may have led to the large
      increases in obesity in the Pima Indians and to smaller parallel changes observed
      worldwide in westernized countries.

PMID- 8296877
TI  - Sexual dimorphism of the human corpus callosum from three independent samples:
      relative size of the corpus callosum.
AB  - Three independent autopsy samples of brains without apparent neuropathology were
      studied to ascertain whether there was sexual dimorphism in the human corpus
      callosum (CC). Using planimetric measurements on midsagittal brain sections,
      several morphometric features of the CC were studied: total callosal area,
      maximum dorsoventral splenial width, the posterior one fifth of the total area of
      the CC (mostly splenium), and brain weight. Ratio data correcting for brain size
      were also studied. In all samples, absolute brain size was larger in males, and
      significantly so. Measurements of splenial dorsoventral width were higher in
      females than males, but not significantly, except in the Australian sample. Total
      callosal area was absolutely higher in the Australian female sample than in
      males, and almost equal in the two American samples, without statistically
      significant differences. The posterior one-fifth area (splenium) was larger for
      females in each of the samples. The variables which were corrected for brain size
      were usually significantly larger in females, although this pattern varied in
      each sample. The statistical pattern of sexual dimorphism for the human CC
      differs from that found in most other neural structures, such as the amygdaloid
      nucleus, cerebellum, hippocampus, and thalamus. The absolute sizes of these
      structures are always significantly larger in males. When corrected for brain
      size, the relative sizes are not significantly larger. The CC is the only
      structure to show a larger set of relative measures in females.

PMID- 8296878
TI  - Relative growth of the limbs and trunk in sifakas: heterochronic, ecological, and
      functional considerations.
AB  - Limb, trunk, and body weight measurements were obtained for growth series of
      Milne-Edwards's diademed sifaka, Propithecus diadema edwardsi, and the golden
      crowned sifaka, Propithecus tattersalli. Similar measures were obtained also for
      primarily adults of two subspecies of the western sifaka: Propithecus verreauxi
      coquereli, Coquerel's sifaka, and Propithecus verreauxi verreauxi, Verreaux's
      sifaka. Ontogenetic series for the larger-bodied P. d. edwardsi and the smaller
      bodied P. tattersalli were compared to evaluate whether species-level differences
      in body proportions result from the differential extension of common patterns of
      relative growth. In bivariate plots, both subspecies of P. verreauxi were
      included to examine whether these taxa also lie along a growth trajectory common
      to all sifakas. Analyses of the data indicate that postcranial proportions for
      sifakas are ontogenetically scaled, much as demonstrated previously with cranial
      dimensions for all three species (Ravosa, 1992). As such, P. d. edwardsi
      apparently develops larger overall size primarily by growing at a faster rate,
      but not for a longer duration of time, than P. tattersalli and P. verreauxi; this
      is similar to results based on cranial data. A consideration of Malagasy lemur
      ecology suggests that regional differences in forage quality and resource
      availability have strongly influenced the evolutionary development of body-size
      variation in sifakas. On one hand, the rainforest environment of P. d. edwardsi
      imposes greater selective pressures for larger body size than the dry-forest
      environment of P. tattersalli and P. v. coquereli, or the semi-arid climate of P.
      v. verreauxi. On the other hand, as progressively smaller-bodied adult sifakas
      are located in the east, west, and northwest, this apparently supports
      suggestions that adult body size is set by dry-season constraints on food quality
      and distribution (i.e., smaller taxa are located in more seasonal habitats such
      as the west and northeast). Moreover, the fact that body-size differentiation
      occurs primarily via differences in growth rate is also due apparently to
      differences in resource seasonality (and juvenile mortality risk in turn) between
      the eastern rainforest and the more temperate northeast and west. Most scaling
      coefficients for both arm and leg growth range from slight negative allometry to
      slight positive allometry. Given the low intermembral index for sifakas, which is
      also an adaptation for propulsive hindlimb-dominated jumping, this suggests that
      differences in adult limb proportions are largely set prenatally rather than
      being achieved via higher rates of postnatal hindlimb growth.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8296879
TI  - Latitudinal and insular variation of skull size in crab-eating macaques
      (primates, Cercopithecidae: Macaca fascicularis).
AB  - Macaca fascicularis is broadly distributed in Southeast Asia across 30 degrees of
      latitude and 35 degrees of longitude (Indochinese Peninsula, Isthmus of Kra,
      Malay Peninsula, Greater and Lesser Sunda Islands, Philippine Islands, and
      numerous small, neighboring islands). The range is divisible into 1) a core area
      comprised of mainland Southeast Asia, Borneo, Sumatra, and Java (large land
      masses interconnected during the last glacial maximum, 18,000 B.P.); 2) shallow
      water fringing islands, which are smaller islands connected to the core area
      during the last glacial maximum; and 3) deep-water fringing islands, which are
      peripheral islands not connected to the core area during the last glacial
      maximum. Skull length was used to study effects of latitude and insularity on
      patterns of size variation. The data are from 802 adult M. fascicularis specimens
      from 140 core-area localities, 63 shallow-water islands, and 29 deep-water
      islands. Sex-specific polynomial regressions of skull length on latitude were
      used to describe skull length variation in the core area. These regressions
      served as standards for evaluating variation among samples from shallow-water and
      deep-water islands. The core area exhibits Bergmannian latitudinal size clines
      through most of the species range. Thus, skull length decreases from about 8
      degrees S (Java) to the equator (Sumatra and Borneo), then increases as far north
      as about 13 degrees N (Isthmus of Kra). Farther north, to the northernmost
      Indochinese localities at about 17 degrees N, skull length in M. fascicularis
      decreases with increasing latitude, contrary to Bergmann's rule. Latitudinal size
      variation in shallow-water fringing islands generally parallels that in the core
      area. However, skull length tends to be smaller than in the core area at similar
      latitudes. Deep-water fringing islands are markedly more variable, with
      relatively small specimens in the Lesser Sunda Islands and relatively large
      specimens in the Nicobar Islands. These analyses illustrate how a primate species
      may vary in response to latitudinal temperature variation and to isolation.

PMID- 8296880
TI  - Brief communication: effect of coca-leaf chewing on salivary progesterone assays.
AB  - Although there is evidence for reduced fertility in Andean and Himalayan
      populations at higher altitudes, factors other than hypoxia may be primarily
      responsible. A valuable approach in the investigation of these fertility
      determinants is the use of salivary steroid assays. However, coca-leaf chewing--a
      ubiquitous practice among high altitude Andean populations--has negative
      consequences for the accurate measurement of ovarian steroids. This report
      evaluates the effects of coca-leaf chewing on assays of salivary progesterone.
      Study participants include naive and habitual users of coca leaf from La Paz and
      El Alto, Bolivia. Approximately 300 saliva samples were collected immediately
      before, during, and after coca-leaf chewing. The series includes samples with and
      without the alkaloid enhancer typically used by coca-leaf chewers. Coca chewing
      produces false salivary progesterone values that mimic luteal phase values. On
      the basis of this study, an appropriate protocol is developed for the collection
      of salivary samples in coca-leaf chewing populations. These results verify the
      feasibility of salivary assays, even for very difficult field conditions, and
      highlight the necessity of establishing suitable collection procedures before
      full field implementation of saliva sampling.

PMID- 8296881
TI  - William Montague Cobb (1904-1990): obituary.

PMID- 8296882
TI  - What for, alcohol research?

PMID- 8296884
TI  - Human brain receptors. Electron micrograph of human striatum showing synaptic
      structures.

PMID- 8296883
TI  - Electroconvulsive therapy of acute manic episodes: a review of 50 years'
      experience.
AB  - OBJECTIVE: The most common indication for electroconvulsive therapy (ECT) is
      major depression. It is less recognized that ECT is effective also in the
      treatment of acute mania. This article aims to provide a comprehensive and
      critical review of the literature on the use of ECT for manic patients. METHOD:
      All published papers in the English language on the use of ECT in acute mania
      that could be found were reviewed with regard to efficacy, frequency and number
      of treatments, bilateral versus unilateral electrode placement, predictors of
      antimanic response, stability of therapeutic response, cognitive consequences,
      and other relevant issues. RESULTS: The evidence indicates that ECT is associated
      with remission or marked clinical improvement in 80% of manic patients and that
      it is an effective treatment for patients whose manic episodes have responded
      poorly to pharmacotherapy. Manic patients do not require a high frequency or
      prolonged course of treatments to respond to ECT. The seizure threshold appears
      to be lower in manic patients than in depressed patients. The issues of relapse
      following response to ECT, cognitive consequences of ECT, and the relative merits
      of unilateral versus bilateral ECT in manic patients require further study.
      CONCLUSIONS: ECT is an effective and safe treatment for acute mania. Remission of
      mania following ECT reflects a primary therapeutic effect rather than a secondary
      consequence of an ECT-induced organic brain syndrome.

PMID- 8296885
TI  - Recovery of brain glucose metabolism in detoxified alcoholics.
AB  - OBJECTIVE: To differentiate withdrawal-related abnormalities in brain glucose
      metabolism among alcoholics from abnormalities that may be irreversible or
      antedate alcohol use, the authors evaluated metabolic recovery during alcohol
      detoxification. METHOD: Regional brain glucose metabolism was measured with
      positron emission tomography and 2-deoxy-2-[18F]fluoro-D-glucose in 10 male
      alcoholics at 8-15 days, 16-30 days, and 31-60 days after last use of alcohol.
      The alcoholics' metabolic values were compared with those of 10 age-matched male
      healthy volunteers. RESULTS: Brain metabolism increased significantly during
      detoxification. There were significant differences in global and regional
      measures between the first and last time points but not between the second and
      third points, suggesting that recovery occurred predominantly within 16-30 days.
      Regional increases in metabolism were greater in the frontal regions. Whereas
      during the first evaluation the alcoholics showed significantly lower metabolism
      in various brain regions than the comparison group, at the end of detoxification
      the alcoholics showed significantly lower absolute and relative metabolic values
      in the basal ganglia and lower relative metabolic values in the parietal cortex.
      Among the alcoholics, but not the comparison group, metabolism in the frontal,
      parietal, and left temporal cortexes was negatively correlated with years of
      alcohol use and with age. CONCLUSIONS: This study shows significant increases in
      brain metabolism during alcohol withdrawal and documents persistent low metabolic
      levels in the basal ganglia of detoxified alcoholics.

PMID- 8296886
TI  - Low level of response to alcohol as a predictor of future alcoholism.
AB  - OBJECTIVE: As part of a search for measurable attributes of an individual that
      might be related to the risk of alcoholism, the author's group previously
      compared 227 sons of alcoholics and 227 matched comparison subjects at the age of
      about 20 years. Forty percent of the men at high risk for alcoholism and less
      than 10% of the comparison subjects demonstrated a low intensity of response to
      alcohol challenge. This article reports the results of the follow-up of the first
      half of this study group almost a decade later. METHOD: Of the men who had been
      tested at about age 20, 223 were about age 30 at this evaluation, which included
      personal and resource-person interviews, record searches, urine toxicology
      screens, and blood level markers of drinking. RESULTS: A low level of response to
      alcohol at age 20 was associated with a fourfold greater likelihood of future
      alcoholism in both the sons of alcoholics and the comparison subjects. Fifty-six
      percent of the sons of alcoholics with the lesser alcohol response developed
      alcoholism during the subsequent decade, compared to 14% of the men in this group
      who had highly sensitive alcohol responses. Neither family history of alcoholism
      nor response to alcohol predicted any other psychiatric diagnoses over the
      subsequent decade, and neither was a significant predictor of any other substance
      use disorder. CONCLUSIONS: In a heavy-drinking society, a lower sensitivity to
      modest doses of alcohol is associated with a significant increase in the risk of
      future alcoholism, perhaps through increasing the chances that a person will
      drink more heavily and more often.

PMID- 8296887
TI  - Short-term psychotherapy of personality disorders.
AB  - OBJECTIVE: The efficacy of short-term psychotherapy has become an area of
      increasing interest. The primary objective of this study was to assess the
      results of two forms of short-term psychotherapy in patients with personality
      disorders. METHOD: Eighty-one patients with personality disorders were randomly
      assigned to brief adaptive psychotherapy, short-term dynamic psychotherapy, or a
      waiting list for therapy. Outcome at termination of therapy for the treatment
      groups and at the end of the waiting period for the waiting list group was
      evaluated by means of ratings of target complaints and scores on the SCL-90 and
      the Social Adjustment Scale. In addition, for 38 of the treated patients, target
      complaints were reevaluated an average of 1.5 years after treatment ended.
      RESULTS: Patients in the two therapy conditions improved significantly on all
      measures in comparison with the patients on the waiting list. There was no
      significant difference between the results in the two therapy conditions. The
      waiting list period averaged approximately 15 weeks; treatment averaged 40 weeks.
      At follow-up, after an average of 1.5 years, target complaint ratings were not
      significantly different from those at the termination of therapy. CONCLUSIONS:
      These data indicate that brief adaptive psychotherapy and short-term dynamic
      psychotherapy are effective for patients with certain types of personality
      disorder and that the two therapy approaches do not differ in overall outcome.

PMID- 8296888
TI  - Temperament and hypercortisolemia in depression.
AB  - OBJECTIVE: The authors examined the relationships among depression severity,
      melancholia, and cortisol level and the relationship between temperament, as
      measured with the Tridimensional Personality Questionnaire, and cortisol level.
      METHOD: Morning and afternoon cortisol levels of 40 healthy comparison subjects
      and 96 patients with major depression were measured. The depressed patients were
      rated for depression severity and melancholia, and they completed the
      Tridimensional Personality Questionnaire. RESULTS: Temperament, especially
      dependence and extravagance, but not depressive symptoms, was the major
      determinant of the hypercortisolemia observed in the depressed patients.
      CONCLUSIONS: For research in biological psychiatry to advance, more attention
      needs to be paid to the individual differences in biology that underlie any state
      dependent biologic dysfunction.

PMID- 8296889
TI  - The long-term stability of depressive subtypes.
AB  - OBJECTIVE: This study used the concept of diagnostic stability to examine the
      validity of three subtypes of major depression. METHOD: Patients with major
      depressive disorder (N = 424) were assigned baseline diagnoses according to
      structured interviews and the Research Diagnostic Criteria. Follow-up evaluations
      took place at 6-month intervals over the next 5 years and annually for an
      additional 3 years. During this period 424, 246, 163, and 96 of the patients who
      had recovered from the index episode had one, two, three, and four recurrences,
      respectively, of major depressive disorder. The kappa statistic was used to
      quantify the likelihood that patients with the psychotic, agitated/retarded, or
      endogenous subtype of depression in a given episode would again manifest that
      subtype in subsequent episodes. RESULTS: The psychotic subtype showed the most
      enduring diagnostic stability across multiple subsequent episodes. Even after
      three intervening episodes, patients with baseline psychotic major depression
      were five times more likely to develop a psychotic depression than were other
      depressed patients. For all three subtypes, diagnostic stability was greater for
      contiguous episodes than for noncontiguous episodes. Psychotic,
      agitated/retarded, and endogenous subtypes showed significant stability after
      control for the bipolar/unipolar and primary/secondary distinctions. The
      endogenous subtype was stable among patients with primary depression but not
      among those with secondary depression. CONCLUSIONS: The psychotic subtype was the
      most valid of the subtypes tested from the perspective of diagnostic stability.
      The fact that stability across adjacent episodes exceeded stability across more
      distantly spaced episodes may reflect state-dependent determinants, and these are
      likely to vary by subtype.

PMID- 8296890
TI  - Symptom differences in major depression, dysthymia, panic disorder, and
      generalized anxiety disorder.
AB  - OBJECTIVE: The authors compared symptom features of specific subtypes of
      depressive and anxiety disorders. METHODS: Psychiatric outpatients with moderate
      levels of psychopathology and DSM-III diagnoses of major depression, dysthymia,
      panic disorder, or generalized anxiety disorder were given five standard measures
      of symptoms of anxiety and depressive disorders. Most of the outpatients were
      white, and most were middle-class. RESULTS: Principal components analysis
      revealed 12 orthogonal symptom components. Discriminant function analysis
      indicated that anxiety was distinguished by specific autonomic arousal symptoms,
      threat-related cognitions, and subjective anxiety and tension. Discriminant
      function analysis also indicated that depression was distinguished by anhedonia,
      cognitions of personal loss and failure, and dysphoric mood. CONCLUSIONS: As
      nosological categories, major depression and panic disorder were better
      differentiated by specific symptom markers than dysthymia and generalized anxiety
      disorder.

PMID- 8296891
TI  - Influence of clinical subtype, sex, and lineality on age at onset of major
      affective disorder in a family sample.
AB  - OBJECTIVE: The authors analyzed data from a family sample ascertained for a
      genetic linkage study of bipolar disorder to address the following questions: Do
      the major clinical subtypes of familial affective disorder have distinct
      distributions of age at onset? What factors other than clinical subtype affect
      these distributions? After controlling for these factors, do the differences in
      age at onset persist among the subtypes? METHODS: Eighty-two families were
      ascertained through a treated proband with bipolar disorder who had a family
      history of two or more affected siblings or one affected sibling and one affected
      parent. After participating in an interview conducted by a psychiatrist using the
      Schedule for Affective Disorders and Schizophrenia--Lifetime Version, 274
      probands and their first-degree relatives were diagnosed as having bipolar I,
      bipolar II, or recurrent unipolar disorder according to Research Diagnostic
      Criteria. Age at first major affective episode and other clinical data were
      collected. RESULTS: Onset age distributions were similar for bipolar I and
      bipolar II disorder but significantly different for recurrent unipolar disorder.
      This finding persisted after adjustment for a significantly earlier onset among
      females. Subjects with affective disorder in both parental lines (bilineal) also
      experienced a significantly earlier onset. Substance abuse, physical illness, and
      sex of the affected parent had no significant impact on onset age. CONCLUSIONS:
      Although differences in age at onset may reflect several factors, these results
      provide indirect support for the view that bipolar I and bipolar II disorders are
      genetically related phenotypes and suggest that bilineal families may be more
      complex than previously assumed.

PMID- 8296892
TI  - Effects of gender and diagnosis on growth hormone response to clonidine for major
      depression: a large-scale multicenter study.
AB  - OBJECTIVE: The authors' goal was to establish, in a large multicenter sample of
      patients classified according to gender and menopausal status, if the growth
      hormone (GH) response to clonidine discriminated patients with episodes of major
      depression from patients with episodes of minor depression. METHOD: The GH
      response to intravenous clonidine administration (150 micrograms) was compared in
      71 male and 140 female patients with major depressive episodes and 47 male and 53
      female patients with minor depressive episodes. These patients were diagnosed
      according to Research Diagnostic Criteria. RESULTS: Differences in the GH
      response to clonidine between diagnostic groups occurred only between male
      patients. These results were found in the group as a whole and in each center.
      The GH responses to clonidine of premenopausal women differed significantly from
      those of postmenopausal women in each diagnostic group. CONCLUSIONS: These
      results confirm that gender and menopausal status are of the utmost importance in
      the interpretation of the clonidine GH test.

PMID- 8296893
TI  - Factors associated with risk for HIV infection among chronic mentally ill adults.
AB  - OBJECTIVE: Chronic mentally ill adults have been found to be at risk for HIV
      infection. The authors investigated the prevalence of HIV risk behaviors among
      psychiatric outpatients. Correlates of HIV risk factors and characteristics of
      patient relationships in which risk occurred were investigated. METHOD:
      Structured interviews were conducted with 95 chronic mentally ill adults from
      urban community support service programs. The interviews focused on sexual and
      substance use behavior, history of HIV risk behaviors, and relationship
      characteristics related to risk. RESULTS: The study showed that 27% of all
      patients had had two or more sex partners in the previous year and 18% had
      received money or drugs for sex. High rates of illicit drug use were also found,
      with frequent use of drugs or alcohol in association with sexual activity.
      Multiple regression analyses showed that use of illicit drugs, meeting sex
      partners in psychiatric clinics, and meeting partners in bars accounted for a
      substantial proportion of the variance in HIV risk behavior. CONCLUSIONS: These
      results suggest an urgent need for HIV prevention programs targeted at urban
      chronic mentally ill adults. Risk-producing characteristics of patient
      relationships and social networks should be addressed in the development of
      prevention interventions.

PMID- 8296894
TI  - Sexual activity and risk of HIV infection among patients with schizophrenia.
AB  - OBJECTIVE: This study sought to determine the frequency and types of sexual
      behavior among patients with schizophrenia and to assess the behavior with
      respect to risk of HIV infection. METHOD: Ninety-five inpatients and outpatients
      with a research diagnosis of schizophrenia underwent a series of face-to-face
      interviews to determine their sexual activity and correlate it with demographic
      characteristics, psychopathology, and medication side effects. RESULTS: Forty
      four percent of the patients had been sexually active in the preceding 6 months,
      and 62% of these had had multiple partners. Sexual activity was associated with
      greater general psychopathology. Having multiple sexual partners was associated
      with younger age, a lower level of functioning, the presence of delusions, and
      more positive symptoms. Of the sexually active patients, 12% reported at least
      one partner who was HIV positive or injected drugs, or both, and 50% had
      exchanged sex for money or goods. Ten percent of the patients had engaged in
      homosexual activity in the preceding 6 months and 22% during their lifetime; the
      frequency was similar among men and women. Consistent condom use was uncommon.
      CONCLUSIONS: A substantial proportion of schizophrenic patients had recent
      histories of sexual abstinence, but an almost equal number were sexually active.
      Sexual activity was usually accompanied by behavior related to HIV risk. Sexual
      activity and having multiple partners were associated with certain measures of
      more severe illness. Younger patients were more likely to have multiple partners
      but were also more likely to use condoms. There is a need for aggressive
      prevention strategies with this population.

PMID- 8296895
TI  - Mood disorders in HIV infection: prevalence and risk factors in a nonepicenter of
      the AIDS epidemic.
AB  - OBJECTIVE: The authors studied the lifetime, initial cross-sectional, and 6-month
      follow-up prevalence of mood disorders in asymptomatic HIV-infected and
      uninfected homosexual men who lived in an area with a low prevalence of HIV. They
      also determined the relationship between current major depression and potential
      depression risk factors. METHOD: Subjects included 98 asymptomatic HIV-infected
      and 71 uninfected homosexual men. Subjects underwent extensive clinical,
      psychiatric, neuropsychological, and laboratory evaluations. RESULTS: Similar
      proportions of HIV-infected and uninfected subjects reported a lifetime (29% and
      45%, respectively), an initial current (8% and 3%), and a 6-month follow-up (9%
      and 11%) history of major depressive disorder. Anxiety disorders were less
      common, with similar proportions of HIV-infected and uninfected subjects
      reporting a lifetime (7% and 13%, respectively), an initial current (3% and 7%),
      and a 6-month follow-up (2% and 5%) history of anxiety disorders. There were no
      differences in the severity of mood symptoms between HIV-infected and uninfected
      subjects. Current major depression at initial visit was significantly associated
      with lifetime history of major depression but not with neuropsychological
      function or vitamin B12 level. CONCLUSIONS: These findings are in agreement with
      previous studies of areas with a high prevalence of HIV. However, the proportion
      of subjects with mood disorders is high compared with general population studies.
      Both HIV-infected and uninfected homosexual men may be at high risk for major
      depression, especially if they have a past history of depression. Moreover, in
      the asymptomatic stage of HIV infection, major depression does not appear to be
      secondary to HIV central nervous system effects or low vitamin B12 levels.

PMID- 8296896
TI  - HIV-associated psychosis: a study of 20 cases. San Diego HIV Neurobehavioral
      Research Center Group.
AB  - OBJECTIVE: Psychosis is an uncommon but serious complication of infection with
      HIV. This article presents the results of a study of HIV-infected individuals
      with psychosis. METHOD: The authors evaluated 20 HIV-infected men who had
      noniatrogenic new-onset psychosis without delirium, current substance abuse, or
      previous psychotic episodes. Clinical, neuropsychological, CSF, magnetic
      resonance imaging, and neuropathologic assessments were made. A comparison group
      consisting of 20 nonpsychotic HIV-infected men matched to the psychotic subjects
      with respect to age, race, years of education, and Centers for Disease Control
      HIV stage was also evaluated. RESULTS: The psychotic patients differed from the
      nonpsychotic comparison subjects in having significantly higher rates of past
      stimulant and sedative/hypnotic abuse or dependence and, at follow-up, a
      significantly higher rate of mortality. They also showed a trend toward greater
      global neuropsychological impairment. CONCLUSIONS: New-onset psychosis may be, at
      least in part, a manifestation of an HIV-associated encephalopathy.

PMID- 8296897
TI  - Serotonergic function in aggressive and nonaggressive boys with attention deficit
      hyperactivity disorder.
AB  - OBJECTIVE: This study was designed to assess central serotonergic (5-HT) function
      in aggressive and nonaggressive boys with attention deficit hyperactivity
      disorder. METHOD: Prolactin response to a challenge dose of the 5-HT agonist d,l
      fenfluramine was assessed in 25 7-11-year-old boys with attention deficit
      hyperactivity disorder who were divided into aggressive and nonaggressive
      subgroups. In addition, the subgroups were compared on plasma catecholamine
      metabolites and platelet 5-HT. RESULTS: The aggressive group had a significantly
      greater prolactin response to the fenfluramine challenge than the nonaggressive
      subgroup. The groups did not differ on peripheral measures of neurotransmitter
      function. CONCLUSIONS: These data suggest that aggressive and nonaggressive
      children with attention deficit hyperactivity disorder differ in central 5-HT
      functioning.

PMID- 8296898
TI  - Assessing positive and negative symptoms in children and adolescents.
AB  - OBJECTIVE: The purpose of this study was to test the reliability and validity of
      a new assessment instrument for positive and negative symptoms in severely
      disturbed children and adolescents (Kiddie-PANSS). METHOD: The Positive and
      Negative Syndrome Scale for adult schizophrenia was modified through successive
      field trials on the basis of developmental characteristics of children and
      adolescents. The scale was then given to 34 inpatients (19 children, mean age =
      9.35 years, and 15 adolescents, mean age = 14.33 years) with DSM-III-R diagnoses
      of schizophrenia, psychosis not otherwise specified, schizoaffective, affective,
      conduct, personality, and developmental disorders determined independently by
      child psychiatrists. All patients with schizophrenia were placed in the
      schizophrenic group, and all others were placed in a general inpatient group. The
      Kiddie-PANSS ratings were given by three trained child psychiatrists after a 30
      35-minute structured interview. The Achenbach Child Behavior Checklist, the Scale
      for the Assessment of Positive Symptoms, and the Scale for the Assessment of
      Negative Symptoms were also administered in order to determine criterion-related
      association. RESULTS: Intraclass correlation coefficients revealed that all
      subscales and total psychopathology were reliably assessed among raters. The
      Kiddie-PANSS and Scale for the Assessment of Positive Symptoms/Scale for the
      Assessment of Negative Symptoms correlated with one another, indicating criterion
      related association. Differences on measures of positive, negative, and general
      psychopathology, as measured by the Kiddie-PANSS, between the patients with
      schizophrenia and the general inpatient group were highly significant.
      CONCLUSIONS: The Kiddie-PANSS shows good interrater reliability and criterion
      related validity. In a cohort of inpatient children and adolescents the scale
      successfully differentiated schizophrenic patients from nonschizophrenic
      patients.

PMID- 8296899
TI  - Treatment goals, continuity of care, and outcome in a day hospital substance
      abuse rehabilitation program.
AB  - OBJECTIVE: Relationships between day hospital treatment goals, self-help group
      participation, and substance use outcome were examined for 180 alcohol- or
      cocaine-dependent male patients in a day hospital Veterans Administration
      substance abuse program. METHOD: The primary goals assessed were completion of
      the day hospital program and participation in posttreatment self-help groups. For
      subjects who completed the day hospital program, progress toward three other
      goals was also assessed: decreased denial, endorsement of 12-Step beliefs, and
      participation in self-help groups during the day hospital program. The outcome
      measures were urine toxicology and self-reports of alcohol or cocaine use at 4-
      and 7-month post-intake follow-up interviews. RESULTS: Day hospital completion
      and participation in posttreatment self-help groups predicted better outcome.
      Self-help participation also predicted outcome after day hospital completion was
      controlled. Among subjects who completed the day hospital program, the other
      three goals did not predict substance use outcome. However, involvement with self
      help groups during the day hospital program and decreases in denial predicted
      continued involvement with self-help groups. CONCLUSIONS: Patients who complete
      day hospital substance abuse rehabilitation and then continue to participate in
      self-help groups are likely to have lower rates of alcohol and cocaine use during
      follow-up. Furthermore, the beneficial effect of self-help group participation
      does not appear to be strictly the result of motivation or some other patient
      characteristic.

PMID- 8296900
TI  - Imipramine antagonism of the panicogenic effects of cholecystokinin tetrapeptide
      in panic disorder patients.
AB  - Eleven panic disorder patients who panicked in response to exogenous
      cholecystokinin tetrapeptide (CCK-4) were rechallenged after chronic treatment
      with imipramine. In the rechallenge the patients displayed a marked reduction in
      the number and intensity of panic symptoms, duration of symptoms, frequency of
      panic attacks, and cardiovascular responsiveness. This study demonstrates that
      imipramine can antagonize the panicogenic effects of CCK-4.

PMID- 8296901
TI  - Triggering the false suffocation alarm in panic disorder patients by using a
      voluntary breath-holding procedure.
AB  - The authors compared the maximal duration of voluntary breath-holding in patients
      with panic disorder (N = 23), patients with generalized social phobia (N = 10),
      and healthy subjects (N = 26). Patients with panic disorder had significantly
      shorter breath-holding durations than either comparison group. Groups did not
      otherwise differ in physiologic response to the breath-holding. Implications for
      a false suffocation alarm in panic disorder are discussed.

PMID- 8296902
TI  - Lack of association between cortisol hypersecretion and nonsuppression on the DST
      in patients with Alzheimer's disease.
AB  - Among 23 patients with Alzheimer's disease, 11 (48%) exhibited cortisol
      hypersecretion (> or = 11.8 micrograms/dl) and nine (39%) displayed cortisol
      nonsuppression on the dexamethasone suppression test. Only four patients
      exhibited both neuroendocrine abnormalities, demonstrating a lack of association
      between these two neuroendocrine disturbances of over 50%. Twenty-two of the 23
      patients were studied for 4 1/2 years, and 14 died during that period. Six of the
      eight surviving patients exhibited cortisol hypersecretion without cortisol
      nonsuppression.

PMID- 8296903
TI  - Effects on behavior of modulation of gonadal function in men with gonadotropin
      releasing hormone antagonists.
AB  - The effects of acute gonadal suppression on sexual function and behavior were
      studied in eight normal men. Administration of a newly developed, potent
      gonadotropin-releasing hormone antagonist induced azoospermia and reduced levels
      of serum testosterone, luteinizing hormone, and follicle-stimulating hormone.
      These effects coincided with a reduction in outward-directed aggression in all
      men. Self-reported measures of anxiety and sexual desire revealed less consistent
      change over time. Measures of anger control, inward-directed anger, and affective
      state were unaffected.

PMID- 8296904
TI  - Relationship between the Tridimensional Personality Questionnaire and DSM-III-R
      personality traits.
AB  - The authors investigated the relationship between Cloninger's personality
      dimensions and DSM-III-R personality traits by comparison of scores on the
      Tridimensional Personality Questionnaire with axis II traits found in structured
      interviews with 99 patients. Consistent with theoretical predictions, axis II
      pathology was significantly related to personality dimensions after the effects
      of axis I disorders were controlled for.

PMID- 8296905
TI  - Serotonergic sensitivity in borderline personality disorder: preliminary
      findings.
AB  - Twelve patients with borderline personality disorder and 15 healthy comparison
      subjects were challenged with single doses of oral m-chlorophenylpiperazine (m
      CPP) and placebo. Following m-CPP, the patients experienced decreased anger and
      fear. Seven of the 12 patients reported a "spacy," "high,"
      depersonalized/derealized experience following m-CPP, which was confirmed by
      clinicians' ratings. Compared with the normal male subjects, the male patients
      with borderline personality disorder had higher cortisol levels and marginally
      blunted prolactin responses after receiving m-CPP. These results suggest
      serotonergic dysfunction in borderline personality disorder.

PMID- 8296906
TI  - Sertraline and extrapyramidal side effects.

PMID- 8296907
TI  - Physical symptoms associated with paroxetine discontinuation.

PMID- 8296908
TI  - Pentoxifylline and panic attacks.

PMID- 8296909
TI  - Treatment of resistant trichotillomania with paroxetine.

PMID- 8296910
TI  - Poststroke pathological laughing and crying.

PMID- 8296911
TI  - Poststroke pathological laughing and crying.

PMID- 8296912
TI  - Carbon-dioxide-induced panic.

PMID- 8296913
TI  - Boundaries in clinical psychiatry.

PMID- 8296914
TI  - Boundaries in clinical psychiatry.

PMID- 8296915
TI  - Boundaries in clinical psychiatry.

PMID- 8296916
TI  - Boundaries in clinical psychiatry.

PMID- 8296917
TI  - Rethinking rethinking Oedipus.

PMID- 8296918
TI  - Rethinking rethinking Oedipus.

PMID- 8296919
TI  - Rethinking rethinking Oedipus.

PMID- 8296920
TI  - Rethinking rethinking Oedipus.

PMID- 8296921
TI  - Rethinking rethinking Oedipus.

PMID- 8296922
TI  - Personality disorder and HIV disease.

PMID- 8296923
TI  - Application of clinical epidemiologic methods to the clinical practice of
      psychiatry.

PMID- 8296924
TI  - Method of recruiting subjects and performance on cognitive tests.
AB  - College students often serve as participants in psychological research. The
      effects of three methods of recruiting subjects for laboratory tests of attention
      and memory were assessed in a series of studies. The performance of students who
      received monetary incentives and the performance of students who received course
      credit incentives were compared with the performance of students recruited from
      classes where research participation was a requirement. Monetary incentives
      resulted in slight, but significant, improvements in performance on tests of
      sustained attention and recognition memory. Course-credit incentives did not
      affect subjects' test performance. Test performance did not differ as a function
      of the time of the semester when studies were conducted. Recruitment issues
      pertinent to departmental subject pools are discussed.

PMID- 8296925
TI  - Effects of foveal stimulation on peripheral visual processing and laterality in
      deaf and hearing subjects.
AB  - This research examines visual field differences in the detection and
      identification of a peripheral stimulus for deaf and hearing subjects, as a
      function of concurrent foveal stimulation. Deaf and hearing subjects were
      presented with peripheral target stimuli (simple geometric shapes) presented
      tachistoscopically to the left or right visual fields under four conditions of
      foveal stimulation: (a) no stimulus; (b) simple geometric shapes; (c) pictorial
      shapes (outline drawings); and (d) orthographic letters. Dependent measures were
      detection response latency and peripheral shape recognition (errors). With error
      data, hearing subjects showed a right field advantage under foveal conditions of
      no stimulus and simple shape stimulus, but a left field advantage with pictorial
      and letter foveal stimuli. Deaf subjects showed the opposite effect, with a left
      field advantage under foveal conditions of no stimulus and simple shape stimulus,
      but a right field advantage with pictorial and letter foveal stimuli. Latency
      data revealed the same pattern of results for hearing subjects, but no
      significant visual field differences for deaf subjects. Results are interpreted
      in terms of differences in hemispheric visual processing used by deaf and hearing
      subjects, as affected by varying conditions of foveal load.

PMID- 8296927
TI  - Violence: the malignancy of our times! Is there hope?

PMID- 8296926
TI  - Rate of false source attributions depends on how questions are asked.
AB  - Lindsay and Johnson (1989) and Zaragoza and Koshmider (1989) report evidence
      indicating that "eyewitness" subjects are much less likely to falsely claim to
      have seen information suggested to them verbally when they receive a source
      monitoring test than when they receive a recognition test requesting only
      identification of the seen information. The present study reports additional
      evidence that source misattributions are affected by the nature of the test.
      Intraub and Hoffman (1992) recently reported the results of a study in which
      subjects claimed to have seen pictures corresponding to scenes that had only been
      described in paragraphs they had read. With this paradigm, we found a similar
      effect using their test, but source confusions were reduced with a test patterned
      after the one used by Lindsay and Johnson. We attribute this difference in
      performance to the different decision criteria evoked by these two tests.

PMID- 8296928
TI  - Childhood experience and adult depression: a review of studies.

PMID- 8296929
TI  - Ann Beattie: emotional loss and strategies of reparation.

PMID- 8296930
TI  - The psychodynamics of fantasy, addiction, and addictive attachments.

PMID- 8296931
TI  - Notes on penetrative identification in femmiphilic transvestism.

PMID- 8296933
TI  - AIDS--displaying the global dynamics.

PMID- 8296932
TI  - Health care reform and public health: weighing the proposals.

PMID- 8296934
TI  - The need to mobilize support for the Wellstone-McDermott-Conyers single-payer
      proposal.

PMID- 8296935
TI  - Alcohol advertising and public health: an urgent call for action.

PMID- 8296936
TI  - Should single-payer advocates support President Clinton's proposal for health
      care reform?

PMID- 8296937
TI  - Commentary: recent reforms in the British National Health Service--lessons for
      the United States.
AB  - President Clinton recently announced his reform plan for health care in the
      United States. The United Kingdom, along with other countries, has already
      enacted reforms in an effort to overcome the basic problem of having insufficient
      funds to provide a health service to meet modern demands. This paper briefly
      describes the recent health reforms in the United Kingdom and highlights some
      lessons for the United States, which include the need to choose procedures that
      should be universally provided. Health reforms that involve some fundamental
      restructuring need to be evaluated everywhere and agreed to by the staff in
      advance.

PMID- 8296938
TI  - Factors influencing the duration of work-related disability: a population-based
      study of Washington State workers' compensation.
AB  - OBJECTIVES: The purpose of this study was to examine factors predictive of
      duration of work-related disability. METHODS: Multivariate survival analysis
      techniques were used to conduct a population-based, retrospective cohort study on
      a random sample of 28,473 workers' compensation claims from Washington State
      filed for injuries occurring in 1987 to 1989. The principal outcome measure was
      length of time for which compensation for lost wages was paid, used as a
      surrogate for duration of temporary total disability. RESULTS: The findings
      suggest that, even after adjusting for severity of injury, older age, female
      gender, and a diagnosis of carpal tunnel syndrome or back/neck sprain
      significantly predict longer duration of disability. Other predictors that were
      stable and significant, but involved lower magnitudes of effect included divorced
      marital status, firm size of fewer than 50 employees, higher country unemployment
      rates, and construction and agricultural work. CONCLUSIONS: Greater disability
      prevention efforts targeting these higher risk subgroups could have significant
      economic and public health effects. The greatest impact may be on claimants who
      remain disabled at 6 months after an injury that did not require hospitalization.

PMID- 8296939
TI  - Circumcision and sexually transmitted diseases.
AB  - OBJECTIVES: New evidence linking lack of circumcision with sexually transmitted
      human immunodeficiency virus revives concerns about circumcision and other
      sexually transmitted diseases. This study was undertaken to assess the
      relationship between circumcision and syphilis, gonorrhea, chlamydial infection,
      genital herpes, nongonococcal urethritis, and exophytic genital warts. METHODS: A
      cross-sectional study of 2776 heterosexual men attending a sexually transmitted
      disease clinic in 1988 was used to investigate the relationship between
      circumcision and sexually transmitted diseases. Subjects with specific sexually
      transmitted diseases and those without such diseases were compared after
      adjustment for age, race, zip code of residence, other sexually transmitted
      diseases, and number of sexual partners. RESULTS: A positive relationship was
      observed between uncircumcised status and both syphilis and gonorrhea. A negative
      relationship was found between warts and lack of circumcision. No apparent
      relationship was noted between uncircumcised status and genital herpes,
      chlamydial infection, or nongonococcal urethritis. CONCLUSIONS: Uncircumcised men
      were more likely than circumcised men to have syphilis and gonorrhea and were
      less likely to have visible warts.

PMID- 8296940
TI  - Employment status and depressive symptoms in middle-aged women: a longitudinal
      investigation.
AB  - OBJECTIVES: This study investigated the psychological effects of paid employment
      and nonemployment, cross-sectionally and longitudinally, in 541 middle-aged
      women. METHODS: Women were seen for an extensive baseline evaluation and were
      reevaluated in an identical manner 3 years later. They were divided into four
      "synthetic" cohorts, based upon employment status at these two assessments.
      RESULTS: At baseline, nonemployed women reported higher levels of depressive
      symptoms than employed women, with nonemployed women with less education, low
      support from family and friends, or low marital satisfaction the most
      symptomatic. Symptoms decreased in women who were nonemployed initially but
      employed at the later exam; in all other groups, symptoms increased. Unlike the
      cross-sectional findings, however, the longitudinal findings showed that women
      who were nonemployed at baseline and had low levels of education, social support,
      or marital satisfaction did not benefit more from subsequent employment than did
      their counterparts who had high levels of these factors. CONCLUSIONS: New paid
      work may have a positive effect on mood for middle-aged women. However, given the
      contradictions between our cross-sectional and longitudinal results, caution
      should be exercised in drawing conclusions from cross-sectional studies that
      likely confound employment status, symptoms, and moderating variables.

PMID- 8296941
TI  - Providing medical care to methadone clinic patients: referral vs on-site care.
AB  - OBJECTIVES: Intravenous drug users are at high risk for medical illness, yet many
      are medically underserved. Most methadone treatment programs have insufficient
      resources to provide medical care. The purpose of this study was to test the
      efficacy of providing medical care at a methadone clinic site vs referral to
      another site. METHODS: Patients with any of four target medical conditions were
      randomized into an on-site group offered medical care at the methadone treatment
      clinic and a referred group offered medical care at a nearby clinic. Entry to
      treatment and use of medical services were analyzed. RESULTS: Of 161 intravenous
      drug users evaluated, 75 (47%) had one or more of the target medical conditions.
      Fifty-one were randomized. In the on-site group (n = 25), 92% received medical
      treatment; in the referred group (n = 26), only 35% received treatment.
      CONCLUSIONS: Providing medical care at a methadone treatment program site is more
      effective than the usual referral procedure and is a valuable public health
      intervention.

PMID- 8296942
TI  - The relationship between mortality and intensity of inpatient alcoholism
      treatment.
AB  - OBJECTIVES: Previous studies have examined mortality in alcoholics receiving
      extended inpatient alcoholism treatment, but few have investigated less intense
      treatment. This study examined mortality within 3 years after discharge from
      varying intensities of inpatient alcoholism treatment. METHODS: Using the
      computerized database of the Department of Veterans Affairs, we identified men
      participating in varying intensities of inpatient alcoholism treatment and
      followed them for 3 years after discharge. Adjusted mortality rates were computed
      and survival analysis was performed to assess the risk of death, adjusting for
      factors that may be related to mortality. RESULTS: The death rate was lower for
      men who completed extended formal inpatient treatment than for those who began,
      but did not complete, inpatient treatment or those who underwent short
      detoxification. Differences among the treatment groups remained after age, race,
      marital status, and disease severity were controlled. CONCLUSIONS: These results
      suggest that extended formal inpatient alcoholism treatment is associated with a
      lower risk of death than less intense forms of inpatient treatment.

PMID- 8296943
TI  - Completion rates of clients discharged from drug and alcohol treatment programs
      in Washington State.
AB  - OBJECTIVES: The primary goal of this study was to analyze completion rates of
      clients in drug and alcohol abuse treatment programs in Washington State and to
      assess the factors associated with treatment completion. A secondary goal was to
      examine the utility of a state information system as a source of evaluative data.
      METHODS: Analyses were conducted of 5827 client records contained in the
      Washington State Substance Abuse Monitoring System, representing a census of
      public clients discharged during the last quarter of 1990 from all state-funded
      alcohol and drug treatment programs in four treatment modalities. Logistic
      regression was performed to determine the independent predictors of treatment
      completion. RESULTS: Completion rates were highest for intensive inpatient
      alcohol treatment (75%) and lowest for intensive outpatient drug programs (18%).
      Factors associated with treatment completion included screening at a referral
      assessment center, education, age, ethnicity, and existence of a secondary drug
      problem. CONCLUSIONS: The fit between clients and treatment programs may be an
      important factor explaining why some clients complete treatment and others drop
      out. State client information systems are an important source of data for
      analyzing treatment completion and other outcomes.

PMID- 8296944
TI  - Ethnicity and the use of outpatient mental health services in a national insured
      population.
AB  - OBJECTIVES: Factors affecting ethnic differences in the use of outpatient mental
      health services are analyzed in an insured, nonpoor population to determine if
      lower use by Blacks and Hispanics persists when socioeconomic and other factors
      are controlled. METHODS: To identify significant predictors of the probability
      and amount of use, insurance claims data for a population of 1.2 million federal
      employees insured by Blue Cross/Blue Shield in 1983 were analyzed with the
      Andersen and Newman model of health service utilization. Logistic and ordinary
      least squares regression models were estimated for each ethnic group. RESULTS:
      Blacks and Hispanics had lower probabilities and amounts of use when compared
      with Whites after controlling for a number of variables. CONCLUSIONS: Since
      ethnic differences in the use of outpatient mental health services exist even in
      an insured, nonpoor population, factors other than lower socioeconomic status or
      insurance coverage--for example, cultural or attitudinal factors and service
      system barriers--are likely responsible. Such findings have policy implications
      in the current climate of health care reform to increase access to care for the
      underserved.

PMID- 8296945
TI  - Mental health status as a predictor of morbidity and mortality: a 15-year follow
      up of members of a health maintenance organization.
AB  - OBJECTIVES: This study sought to relate preexisting depression, worries, affect
      balance, and mental health symptoms to subsequent risk of morbidity and
      mortality. METHODS: A random sample of members of a health maintenance
      organization were interviewed at home in a 1970/71 survey. Baseline psychological
      measures from that survey were then related to 15-year mortality and first
      incidence of cancer, heart disease, hypertension, stroke, functional
      gastrointestinal disease, and hyperimmune diseases. RESULTS: Baseline depression
      and the Langner Mental Health Index predicted incidence of functional
      gastrointestinal and hyperimmune diseases. The relationship of the Langner index
      to hyperimmune diseases was particularly strong; mortality, cancer, heart
      disease, hypertension, and stroke incidence were not related to that index.
      Except for affect balance, which was worst in the elderly, indications of
      psychological dysfunction were strongest in the young. CONCLUSIONS: Psychological
      indices detected increased risk for functional gastrointestinal and hyperimmune
      diseases but were not related to mortality risk. Further research is needed to
      disaggregate relationships of the specific conditions that were included in the
      hyperimmune group. Functional gastrointestinal disease might be preventable with
      early attention to depressed persons and to those scoring high on the Langner
      index.

PMID- 8296946
TI  - Dementia-free life expectancy in France.
AB  - OBJECTIVES: Increasing concern with the quality of gains in life years has led to
      the development of a new synthetic indicator of population health:health
      expectancy. Until now, calculations have been made for physical disabilities
      only. A first estimate of mental health expectancy is presented: dementia-free
      life expectancy. METHODS: Sullivan's method was used to calculate dementia-free
      life expectancy for a random representative sample of 4134 persons over 65 years
      of age in the Bordeaux region of France. The diagnosis of senile dementia was
      made in two stages, based on Diagnostic and Statistical Manual of Mental
      Disorders (DSM-III-R) criteria. RESULTS: At 65 years of age, a person's dementia
      free life expectancy is 16.9 years within a total life-expectancy of 17.7 years;
      it decreases with age in parallel with the decrease in total life expectancy so
      that life expectancy with dementia stays constant at 0.8 years. Although dementia
      prevalence increases with age, if the prevalence is adjusted for mortality, the
      largest number of persons with dementia are in their early eighties. At each age
      women have a higher dementia-free life expectancy. CONCLUSIONS: Trends in
      dementia-free life expectancy are similar to those found in disability-free life
      expectancy. Because the dementia prevalence rates used in this estimate resemble
      a general model derived from meta-analysis, it can be assumed that similar
      results will be found in other Western countries with similar mortality rates.

PMID- 8296947
TI  - The prevalence and demographics of pathological gamblers: implications for public
      health.
AB  - OBJECTIVES: A study of pathological gambling in five states provides information
      needed to address the public health threat that the expanding availability of
      legalized gambling poses to at-risk groups in the general population. METHODS:
      Over the course of this project, epidemiological data were collected to determine
      the prevalence of probable pathological gambling in the general population in
      each study state and demographic data were collected from pathological gamblers
      entering treatment programs in each state. RESULTS: Among the states surveyed,
      the availability of and involvement in gambling differ significantly, as does the
      prevalence of pathological gambling. Despite these differences, the demographics
      of pathological gamblers in these states are similar. Like those in the general
      population, pathological gamblers entering treatment in each state are similar.
      However, pathological gamblers entering treatment do not represent the full
      spectrum of individuals in the general population who experience gambling-related
      problems. CONCLUSIONS: These findings raise a number of issues, including the
      potential impacts of continued gambling legalization on the overall rate of
      gambling problems in the general population and on specific at-risk groups,
      including women, minorities, and children. They thus have implications for policy
      and program decisions now being made throughout the United States.

PMID- 8296948
TI  - Sedatives and hypnotics in Stockholm: social factors and kinds of use.
AB  - OBJECTIVES: The aims of the study were (1) to estimate prevalence rates of
      current, regular, and long-term use of sedatives and hypnotics and the incidence
      of regular use in an urban population and (2) to study the association between
      such use of drugs and sociodemographic factors, symptoms of disease, and alcohol
      consumption. METHODS: Data on drug use in a random sample of 6217 adults in
      Stockholm County were analyzed with logistic regression. RESULTS: The prevalence
      rate for current use of sedatives or hypnotics was 12.8% among men and 18.6%
      among women; the rate for regular use was 3.7% among males and 4.7% among
      females. The odds ratio for current use increased with age and was higher among
      unemployed persons and disability pensioners, high consumers of alcohol, persons
      with an increased level of symptoms, and widows. More than 25% of the persons who
      had used sedatives or hypnotics during the previous 2 weeks were regular users 6
      months later. For persons aged 25 through 64 years, the annual incidence rate was
      1.8% among men and 2.7% among women. CONCLUSIONS: The comparatively low incidence
      and high prevalence of regular use implies that long-term use of sedatives and
      hypnotics is common.

PMID- 8296949
TI  - Societal-level predictors of groups' drinking patterns: a research synthesis from
      the Collaborative Alcohol-Related Longitudinal Project.
AB  - OBJECTIVES: Period effects of per capita consumption of alcohol and divorce rates
      are assessed for change in quantity and frequency among age/sex groups in
      multiple longitudinal studies. METHODS: Twenty-five studies of quantity and 29
      studies of frequency are used. Studies are from 15 nations and cover periods of 1
      to 21 years. Models predict the standardized mean difference for quantity and
      frequency based on period effects and group-level and methodological variables.
      RESULTS: When both the period effects of per capita consumption and the divorce
      rate are considered, the divorce rate significantly predicts change in quantity
      and frequency. An increase in the divorce rate is associated with a stronger
      decrease in frequency among younger people; men are more likely than women to
      decrease their frequency of drinking when divorce rates rise. CONCLUSIONS:
      Multiple societal-level factors should be considered critical in influencing the
      drinking patterns of groups. These results suggest that an increase in the
      divorce rate is associated with more "dry" social contexts, characterized
      possibly by drinking patterns of a more "volitive" nature (i.e., heavier quantity
      per occasion and less frequent drinking).

PMID- 8296950
TI  - Television beer advertising and drinking knowledge, beliefs, and intentions among
      schoolchildren.
AB  - OBJECTIVES: The relationships between television beer advertising and drinking
      knowledge, beliefs, and intentions were investigated in a survey of
      schoolchildren. The research was guided by a theoretical model specifying that
      awareness of advertising, and not mere exposure, is necessary for it to have an
      effect on beliefs or behaviors. METHODS: Participants were a random sample of 468
      fifth- and sixth-grade schoolchildren from a northern California community. Data
      were collected in the home with a combination of self-administered questionnaires
      and structured interviews. RESULTS: Nonrecursive statistical modeling indicated
      that awareness of television beer advertising was related to more favorable
      beliefs about drinking, to greater knowledge of beer brands and slogans, and to
      increased intentions to drink as an adult. The effects of advertising awareness
      on knowledge, beliefs, and intentions were maintained when the reciprocal effects
      of beliefs, knowledge, and intentions on awareness were controlled. CONCLUSIONS:
      The findings suggest that alcohol advertising may predispose young people to
      drinking. As a result, efforts to prevent drinking and drinking problems among
      young people should give attention to countering the potential effects of alcohol
      advertising.

PMID- 8296951
TI  - Risk factors for homelessness among schizophrenic men: a case-control study.
AB  - OBJECTIVES: To identify risk factors for homelessness among the severely mentally
      ill, we conducted a case-control study of 100 indigent schizophrenic men meeting
      criteria for literal homelessness and 100 such men with no homeless history.
      METHODS: Subjects were recruited from shelter, clinic, and inpatient psychiatric
      programs in Upper Manhattan. Clinical interviewers employed standardized research
      instruments to probe three domains of risk factors: severity of mental illness,
      family background, and prior mental health service use. RESULTS: Homeless
      subjects showed significantly higher levels of positive symptoms, higher rates of
      a concurrent diagnosis of drug abuse, and higher rates of antisocial personality
      disorder. Homeless subjects experienced greater disorganization in family
      settings from birth to 18 years and less adequate current family support. Fewer
      homeless subjects than subjects in the never-homeless comparison group had a long
      term therapist. These differences remained when demographic variables were
      adjusted statistically. CONCLUSIONS: Homeless schizophrenic men differed from
      their domiciled counterparts in all three domains we investigated; family
      background, nature of illness, and service use history. Findings are discussed in
      relation to policy and programs for the severely mentally ill.

PMID- 8296952
TI  - AIDS, HIV infection, and illicit drug use within inner-city families and social
      networks.
AB  - OBJECTIVES: Drug use is commonly depicted and treated as an individual problem.
      This study describes the extent of drug use, human immunodeficiency virus (HIV)
      infection, and acquired immunodeficiency syndrome (AIDS) among drug users' sexual
      partners and family and household members in order to broaden considerations of
      risk. METHODS: Social network charts and structured interviews were administered
      to 126 women (predominantly African American and Latino) enrolled in methadone
      treatment. The charts elicited the prevalence of drug use and HIV infection among
      subjects' family and household members. RESULTS: Drug use and HIV/AIDS permeated
      subjects' sexual, familial, and household relationships. More than half of the
      women who resided with a sexual partner reported that their partners currently
      used drugs. Almost one third of the subjects' siblings were drug users. Of the
      715 total siblings (all subjects plus their siblings), 69 (9.7%) were known to be
      HIV positive or to have an AIDS diagnosis. CONCLUSIONS: The sexual, familial, and
      household expressions of drug use underscore the notion that drug use and
      attendant risks, including but not limited to HIV infection, might be usefully
      viewed and treated as an inter- and intracommunity problem rather than as an
      exclusively individual one.

PMID- 8296954
TI  - Chronic fatigue syndrome: have flawed assumptions been derived from treatment
      based studies?
AB  - Chronic fatigue syndrome is a disabling disorder that has been studied primarily
      in clinical settings. In the absence of an adequate epidemiological database,
      cultural stereotypes have influenced the characterization of chronic fatigue
      syndrome as "the yuppie flu," similar to the 19th century characterization of
      neurasthenia as a disease of the affluent. The limited epidemiological data
      available and the overall medical-sociological literature call this assumption
      into question. Only a community "true" prevalence study that is unbiased by help
      seeking and access to health care can provide an accurate assessment of the risk
      factors for and the public health ramifications of this disease.

PMID- 8296953
TI  - Injecting risk behavior among drug users in Amsterdam, 1986 to 1992, and its
      relationship to AIDS prevention programs.
AB  - OBJECTIVES: Serial, cross-sectional trends in injecting risk behavior were
      studied among drug users from 1986 to 1992. METHODS: From a cohort study in
      Amsterdam, 616 intake visits of drug users who had injected in the 6 months
      preceding intake were selected. RESULTS: The proportion of drug users who
      reported borrowing and lending used injection equipment and reusing
      needles/syringes (in the previous 6 months), continuously declined from 51% to
      20%, from 46% to 10% and from 63% to 39%, respectively. In multivariate analysis,
      it appeared unlikely that a selective recruitment of participants over time was
      responsible for these trends. Participants, recruited later in time, had been
      previously tested for human immunodeficiency virus (HIV) more often, had received
      daily methadone less often, and had obtained a higher proportion of new needles
      via exchange programs. Indications were found that (1) voluntary HIV testing and
      counseling leads to less borrowing, lending, and reusing equipment; and (2)
      obtaining needles via exchange programs leads to less reusing needles/syringes.
      It appeared that nonattenders of methadone and exchange programs have reduced
      borrowing and lending to the same extent as attenders. CONCLUSIONS:
      Methodologically, evaluating specific measures is difficult. However, the
      combination of various preventive measures in Amsterdam is likely to be
      responsible for the observed decrease in injecting risk behavior.

PMID- 8296955
TI  - The provision and use of mental health services in nursing homes: results from
      the National Medical Expenditure Survey.
AB  - Data from the Institutional Population Component of the National Medical
      Expenditure Survey were used to provide national estimates of annual mental
      health service provision and use in nursing homes. In addition, the relationship
      between service provision and setting characteristics such as ownership, size,
      Medicaid certification, and chain status was examined. Although more than three
      quarters of residents with a mental disorder resided at a nursing home that
      provided counseling services, fewer than one fifth actually received any mental
      health services within the year.

PMID- 8296956
TI  - Psychotic inpatients' social class and their first admission to state or private
      psychiatric Baltimore hospitals.
AB  - Social class differences were investigated among patients admitted to public and
      private psychiatric hospitals. Participants included first admission White
      psychotic men admitted to Baltimore metropolitan area hospitals between 1983 and
      1989. After adjusting for age and diagnosis, patients with low levels of
      skills/credentials were found to be more likely than patients with higher levels
      to be admitted to state psychiatric hospitals. These findings underscore the
      persistence of social class as a determinant of differences in the use of
      psychiatric care.

PMID- 8296957
TI  - Psychiatric and substance abuse disorders among male urban jail detainees.
AB  - This paper presents prevalence rates by race/ethnicity and age for nine
      psychiatric and substance use disorders found in a random sample of 728 male jail
      detainees. Two thirds of the sample detainees had had a disorder other than
      antisocial personality during their lifetimes; half of these had had an episode
      within 2 weeks of the interview. More than 30% currently had either a severe
      mental disorder or a substance use disorder. Detainees with severe mental
      disorders or substance use disorders were most often in jail because they had
      committed nonviolent crimes. Policy implications of the results are discussed.

PMID- 8296958
TI  - Enhancing the self-report of alcohol consumption in the community: two
      questionnaire formats.
AB  - Two questionnaire formats for assessing alcohol consumption in a community sample
      were compared. Subjects completed the Semi-Quantitative Food Frequency
      Questionnaire and a questionnaire specifically targeting alcohol use. Across all
      alcoholic beverages, subjects reported lower consumption on the alcohol
      questionnaire than on the food frequency questionnaire. The results suggest that
      food frequency questionnaires may provide a better means for enhancing self
      report of alcohol use than questionnaires that target solely alcohol intake.

PMID- 8296959
TI  - The frequency and nature of alcohol and tobacco advertising in televised sports,
      1990 through 1992.
AB  - This study examines the frequency and nature of alcohol and tobacco advertising
      in a random sample of 166 televised sports events representing 443.7 hours of
      network programming broadcast from fall 1990 through summer 1992. More
      commercials appear for alcohol products than for any other beverage. Beer
      commercials predominate and include images at odds with recommendations from
      former Surgeon General Koop. The audience is also exposed to alcohol and tobacco
      advertising through the appearances of stadium signs, other on-site promotions,
      and verbal or visual brief product sponsorships. Moderation messages and public
      service announcements are rare.

PMID- 8296960
TI  - The illegal sale of cigarettes to US minors: estimates by state.
AB  - Data available from recent national surveys on the cigarette consumption and
      purchasing practices of teenage smokers were used to generate state-specific
      estimates of the number of teenage smokers and cigarette sales to minors. In
      1991, approximately 2.7 million teenage cigarette smokers consumed an average of
      28.3 million cigarettes per day (516 million packs per year). An estimated 255
      million packs of cigarettes were sold illegally to minors in 1991. To make
      cigarettes and other tobacco products less accessible to minors, policymakers
      should consider implementing various legislative and economic measures such as
      banning cigarette vending machines and raising tobacco excise taxes.

PMID- 8296961
TI  - A pilot syringe exchange program in Washington, DC.
AB  - The Washington, DC City Council authorized a pilot syringe exchange program to
      operate for only 60 days at a single drug abuse treatment facility in the
      District. Only adults on the waiting list for treatment were eligible (n = 467).
      Of the 33 who enrolled, median duration of drug injection was 18 years. Twenty
      seven participants denied needle sharing. Of 209 needles distributed, 69% were
      returned. Low enrollment might have been due to restrictive entry criteria,
      inconvenient location, incorrect syringe size, and attitudes of treatment staff.
      For future efforts to have a public health impact, wider accessibility will be
      needed.

PMID- 8296962
TI  - Is liquor intoxicating? Scientists, prohibition, and the normalization of
      drinking.
AB  - The reliance of current advocates of recreational drug legalization on parallels
      between "drug prohibition" and the repudiated experiment of National Prohibition
      in the 1920s invites renewed attention to the history of the legalization and
      normalization of drinking. A new scientific conception of the nature and effects
      of alcohol formed an important element in both the politics of repeal and the
      ensuing legitimation of alcohol consumption. The industrial toxicologist Yandell
      Henderson argued that alcohol should be considered analogous to carbon monoxide-
      clearly a poison, yet a normal part of civilized life and only problematic above
      a determinable and manageable exposure threshold. This argument had political
      force in the early 1930s as part of the contention that beer was not an
      "intoxicating liquor." It was more broadly persuasive because it was consistent
      with Americans' experience with industrial poisons, for which exposure levels had
      been set by toxicologists such as Henderson. This historical perspective
      illuminates the more recent reassessment of the risks of alcohol consumption. It
      also challenges the applicability of the model of the normalization of drinking
      to proposals to legalize cocaine and opiates.

PMID- 8296963
TI  - Using race-specific community programs to increase organ donation among blacks.

PMID- 8296964
TI  - Clinica Tibas: a public-private partnership for health care delivery in Costa
      Rica.

PMID- 8296965
TI  - Assessing community health concerns and implementing a microgrant program for
      self-help initiatives.

PMID- 8296966
TI  - Participation in treatment decision might affect hysterectomy rates.

PMID- 8296967
TI  - Defending HIV seroprevalence surveys.

PMID- 8296968
TI  - Perceived job stress, job strain, and hypertension.

PMID- 8296969
TI  - The efficacy of testing and counseling in limiting HIV transmission.

PMID- 8296970
TI  - The relational matrix: the contributions of infant research to a psychodynamic
      developmental psychology.

PMID- 8296971
TI  - Subjectivity in parent-infant relationships: contributions from attachment
      research.

PMID- 8296972
TI  - Attachment and the problem of coherence: implications for treating disturbed
      adolescents.

PMID- 8296973
TI  - Attachment, personality, and psychopathology: relationship as a regulatory
      context in adolescence.

PMID- 8296974
TI  - The interpretive community of self.

PMID- 8296975
TI  - Relatedness and autonomy in adolescence: links with ego development and family
      interactions.

PMID- 8296976
TI  - Education and social reality: present and future.

PMID- 8296977
TI  - The relational self: implications for adolescent development.

PMID- 8296978
TI  - The epigenesis of relational systems: a revised developmental perspective.

PMID- 8296979
TI  - Multiple personality disorder in adolescence.

PMID- 8296980
TI  - Malignant memories: signatures of violence.

PMID- 8296981
TI  - Attentional disorders in adolescence: integrating psychoanalytic and
      neuropsychological diagnostic and developmental considerations.

PMID- 8296982
TI  - Education and poverty: problems and possibilities.

PMID- 8296983
TI  - Psychoanalytic developmental perspectives on the treatment of a young adult.

PMID- 8296984
TI  - Adolescent suicide: etiology and treatment.

PMID- 8296985
TI  - Physical symptoms as a mask for emotional disorder in adolescents.

PMID- 8296986
TI  - Childhood symptoms of maladjustment: a prognostic indicator of adolescent
      psychopathology.

PMID- 8296987
TI  - The role of interdisciplinary consultation: countertransference during the acute
      psychiatric hospitalization of the adolescent.

PMID- 8296988
TI  - Adolescent violence and the adolescent self.

PMID- 8296989
TI  - Severely emotionally disturbed children: foreseeing, avoiding, and ameliorating
      their pain.

PMID- 8296990
TI  - Creativity and productivity in adolescence.

PMID- 8296992
TI  - Therapeutic effects of a near-death experience in anorexia nervosa.

PMID- 8296991
TI  - Kibbutz Sasa: nurturing children at risk.

PMID- 8296994
TI  - Financing child and adolescent mental health care.

PMID- 8296993
TI  - Clinical perspectives on managed care.

PMID- 8296995
TI  - Adolescent day treatment: an alternative for the future.

PMID- 8296996
TI  - Day treatment for serious mental illness.

PMID- 8296997
TI  - Diagnostic difficulties in adolescent psychiatry: where have we been, and where
      are we going?

PMID- 8296998
TI  - G. Stanley Hall and the invention of adolescence.

PMID- 8296999
TI  - On seeing: the problem of the double blind.

PMID- 8297000
TI  - 32P-labeled opioid peptides with high affinity for the delta-opioid receptor.
AB  - We describe a mild and convenient labeling method for obtaining opioid
      radioligands which exhibit high specific activity together with a high affinity
      for the delta-opioid receptor. We chemically synthesized and tested the affinity
      of enkephalin- and deltorphin-like peptides that contain a phosphorylation site
      at their C-terminus. The peptide YdAGFLTPRRASLGC (peptide B), labeled to 700
      Ci/mmol in the presence of cAMP-dependent protein kinase and [gamma-32P]ATP,
      bound to the receptor with high affinity (Kd = 3.62 +/- 0.29 nM). This peptide
      was also chemically coupled to bovine serum albumin and provided a multivalent
      opioid protein (B-BSA) with interesting properties: compared with peptide B, B
      BSA was a better substrate for the kinase (100% 32P incorporation, sp act > or =
      7000 Ci/mmol when labeled) and a better ligand for the receptor (Kd = 0.20 +/-
      0.02 nM). The concept of peptide extension by a short phosphorylatable sequence
      should be more generally applicable to other small peptidic hormones or
      neurotransmitters and provide useful probes for biochemical studies and
      expression cloning of membrane receptors.

PMID- 8297001
TI  - Quantitative methods for scoring cell migration and invasion in filter-based
      assays.
AB  - The ability of cells to traverse pores in a biocompatible filter provides means
      for examining cell chemoattraction. Filter-based assays also permit rapid,
      quantitative assessment of the in vitro migratory and invasive potential of tumor
      cells. Scoring migration has relied on visual counting of stained cells which
      appear on the underside of the filter and determining a true percentage score
      involves arduous counting of cells on both filter surfaces. Visual counting of
      random fields may be unreliable, and counting all fields is laborious. In the
      present study we developed and compared two alternative methods for scoring cell
      numbers in filter-based assays, a colorimetric assay of toluidine blue binding,
      and a radioassay of cells prelabeled with [3H]thymidine. Each method was
      evaluated for sensitivity, variability, ease of use and efficiency, and
      suitability for use in assays of cell migration and invasion. The radiolabeling
      method proved to be sensitive and reliable and was the most efficient technique.
      Although less sensitive and specific, the colorimetric dye method offered a rapid
      and reliable, nonradioactive alternative with the distinct advantage of
      preserving intact cultures for follow-up visual assessments. We conclude that
      colorimetric and radiolabel scoring of filter-based assays are reliable and
      efficient semiautomated methods which provide means to obtain more complete
      assessments of cell migration and invasion.

PMID- 8297002
TI  - Measurement of both cyclic [3H]AMP and cyclic [3H]GMP in cultured vascular smooth
      muscle cells labeled with [3H]hypoxanthine: use in studies of cardiovascular
      drugs.
AB  - We describe a method for prelabeling cultured vascular smooth muscle cells that
      permits rapid and accurate measurements of changes in the amounts of cyclic AMP
      and of cyclic GMP in 5 x 10(5) cells. This procedure utilizes [3H]hypoxanthine to
      radiolabel both the adenine and guanine nucleotide pools and simple column
      chromatographic steps to isolate and separate the 3H-labeled cyclic nucleotides.
      The application of the method to studies of the actions of cardiovascular drugs
      on vascular smooth muscle cells is illustrated by measurements of the effects of
      isoproterenol, nitroprusside, and inhibitors of cyclic AMP phosphodiesterases on
      the cyclic nucleotide levels in these cells. If required, the mass amounts of
      cyclic AMP and cyclic GMP present could be determined by measurement of the
      specific radioactivities of the precursor [3H]ATP and [3H]GTP, respectively. The
      cyclic nucleotide values calculated by the latter method were almost identical to
      those obtained with larger numbers of cells using commercially available
      radioimmunoassays, thus validating the prelabeling assays. The method described
      should be applicable to any type of cultured cell that can utilize
      [3H]hypoxanthine to replenish its ATP and GTP pools.

PMID- 8297003
TI  - Membrane protein topology determination by proteolysis of maltose binding protein
      fusions.
AB  - A method is presented for determining the topology of Escherichia coli inner
      membrane proteins that is based on proteolysis of fusion proteins between maltose
      binding protein (MBP) and the membrane protein of interest. Fusion proteins are
      constructed wherein the MBP domain is fused upstream of the membrane protein
      domain. A secreted MBP domain is attached to the protein if its N-terminus
      resides in the periplasm. A cytosolic MBP domain (MBP delta 2-26) is attached to
      the protein when its N-terminus resides in the cytoplasm. The method has been
      developed using a fusion protein in which a secreted MBP domain is attached to
      the pBR322 tetracycline resistance protein at its first periplasmic loop. Fusion
      proteins are subjected to partial proteolysis in membrane vesicles under
      conditions where digestion does not occur in MBP. The mixture of digestion
      products is analyzed by Western immunoblotting using anti-MBP antiserum to detect
      cleavage fragments. Sites of digestion in the membrane protein are identified by
      comparing the mobilities of digestion products to truncated fusion standards that
      terminate at defined locations within the membrane protein domain. The technique
      has the advantage that neither overexpression of the protein nor high-quality
      antiserum to it are required for detection of protease fragments. Furthermore,
      the method can be applied to screen membrane proteins for structure alterations
      that have been introduced deliberately into them.

PMID- 8297004
TI  - Determination of erythrocyte aldehyde dehydrogenase activity by high-performance
      liquid chromatography.
AB  - An ion-paired high-performance liquid chromatographic method was developed for
      the determination of erythrocyte aldehyde dehydrogenase activity. This method
      does not require pretreatment to remove hemoglobin from the hemolysate before
      enzyme reaction is initiated. In addition, the advantage with this high
      performance liquid chromatographic method is that erythrocyte aldehyde
      dehydrogenase activity can be measured using whole blood without either
      separation or washing of erythrocytes. Therefore, it can be easily used in the
      determination of erythrocyte aldehyde dehydrogenase activity, which is an
      indication of excess alcohol consumption.

PMID- 8297005
TI  - Procedures for the isolation and quantification of the intermediates of the
      mevalonic acid pathway.
AB  - Procedures for the isolation and analysis of all 11 intermediates of the
      mevalonic acid pathway from acetyl-CoA through geranylgeranyl pyrophosphate were
      developed. Both acid-labile and base-labile metabolites are simultaneously
      extracted with good recoveries into 7 M urea at neutral pH and low temperature to
      minimize hydrolytic and degradative enzyme losses, and the extract is partially
      purified by adsorption and desorption in high yield from an anion-exchange
      membrane. With the use of internal standards, the pathway intermediates are
      subsequently separated and quantified by reversed-phase ion-pair HPLC with on
      line radiodetection. Permeable secretory cells specialized for monoterpene
      biosynthesis were isolated from peppermint (Mentha x piperita) leaves and
      employed as a model system to test the analytical protocols by examining the
      incorporation of [14C]pyruvate, [14C]mevalonate, and [3H]isopentenyl
      pyrophosphate as precursors. This simple new method should be readily adaptable
      to a wide range of cell and tissue types that can be administered basic metabolic
      precursors, and should allow measurements of both flux and steady-state levels of
      the intermediates of the mevalonic acid pathway.

PMID- 8297006
TI  - Oligosaccharide mapping of fungal glucan synthase product by high-performance
      anion-exchange chromatography.
AB  - Crude membrane preparations of fungi contain the enzyme glucan synthase (EC
      2.4.1.34) which produces a polymer of glucose linked through 1,3-beta-glycosidic
      bonds. This polymer is a major structural element of the fungal cell wall.
      Preparations of glucan synthase are contaminated with the enzyme glycogen
      synthase (EC 2.4.1.11). Glycogen synthase forms the storage carbohydrate
      glycogen, a polymer of glucose consisting of mainly 1,4-alpha-glycosidic linkage.
      Both enzymes utilize uridine diphosphoglucose as substrate. Discrimination of
      glucan synthase from glycogen synthase activity has relied upon the inclusion of
      glycogen-degrading enzymes in the crude reactions. The polysaccharide reaction
      products of glucan synthase assays have been characterized by their
      susceptibility to enzymatic degradation by various glucanohydrolases. These
      degradative enzymes are impure and inclusion of appropriate control
      polysaccharides often leads to ambiguous results. A method for comparative
      qualitative analysis of polysaccharides formed in fungal glucan synthase
      reactions has been developed using high-performance anion-exchange
      chromatography. Using this method, polymers of glucose with 1,3-beta-glycosidic
      linkage and 1,4-alpha linkage can be readily distinguished. This method has been
      applied to map oligosaccharides derived by partial acid hydrolysis from fungal
      glucan synthase reaction products from Candida albicans protoplasts prepared by
      two different methods.

PMID- 8297007
TI  - Administration of oligonucleotides to cultured cells by calcium phosphate
      precipitation method.

PMID- 8297008
TI  - Rapid autoradiography of sequencing gels using imaging plates.

PMID- 8297009
TI  - A centrifugal separation procedure detects moderate affinity cGMP binding sites
      in membrane-associated proteins and permeabilized cells.

PMID- 8297010
TI  - Chromatographic analysis of lysosomal degradation of unlabeled native proteins in
      vitro by fluorescein isothiocyanate labeling.
AB  - Fluorescein isothiocyanate (FITC) has high affinity to both Toyopearl HW-40 and
      Sephadex G-25 gel. FITC-labeled amino acids showed no affinity for Sephadex G-25
      whereas FITC-labeled proteins had no affinity. They were eluted in the order FITC
      labeled proteins, FITC-labeled amino acids, and free FITC from a small combined
      column of Sephadex G-25/Toyopearl HW-40, which was prepared by layering a small
      volume of Toyopearl HW-40 gel on top of a larger volume of Sephadex G-25 gel.
      These findings were applied to analyzing the degradation of various unlabeled
      native proteins including L-lactate dehydrogenase (LDH) and rat serum albumin by
      total lysosomal enzymes in vitro. After degradation, proteins and amino acids
      released from a substrate protein were labeled with FITC and eluted through the
      small combined column. FITC-labeled amino acids were easily separated from FITC
      labeled proteins and free FITC, and their production increased with degradation
      time and was markedly suppressed by the proteinase inhibitor leupeptin. The
      degradation of native LDH was also accompanied by inactivation and the
      disappearance of the 35-kDa subunit. This procedure is a simple and useful method
      for studying the proteolytic degradation of various unlabeled proteins by total
      lysosomal enzymes.

PMID- 8297011
TI  - Selective inactivation of eukaryotic beta-galactosidase in assays for inhibitors
      of HIV-1 TAT using bacterial beta-galactosidase as a reporter enzyme.
AB  - Bacterial beta-galactosidase is one of several reporter enzymes used in studying
      the transcriptional activity of eukaryotic promoters. Although it is one of the
      easiest and least expensive enzymes to assay, its use has been limited because of
      its low sensitivity, which is due in part to endogenous levels of beta
      galactosidase in many eukaryotic cells. In this study, we compared the pH and
      salt requirements, as well as the heat stability, of bacterial and eukaryotic
      beta-galactosidase in order to identify conditions which would inhibit the beta
      galactosidase enzyme endogenous to eukaryotic cells without adversely affecting
      the activity of either purified bacterial beta-galactosidase or reporter beta
      galactosidase produced after transfection of expression vectors into eukaryotic
      cells. Heat treatment at 50 degrees C for 1 h inactivated the beta-galactosidase
      activity endogenous to several eukaryotic cell lines by as much as 40-fold
      without adversely affecting the activity of bacterial beta-galactosidase. This
      treatment increased the sensitivity of this reporter enzyme and allowed the
      development of a rapid and quantifiable screening assay for HIV-1 tat inhibitors.

PMID- 8297012
TI  - Development of choline and acetylcholine Pt microelectrodes.
AB  - Choline (Ch) and acetylcholine (Ach) microenzyme sensors were developed based on
      the immobilization of choline oxidase (ChO) and acetylcholinesterase (AchE) at
      the tip of a 25-micron Pt wire sealed in glass. Several immobilization procedures
      were tested, including code-position of the enzyme/s with an electropolymer and
      cross-linking with glutaraldehyde. The various electropolymers used were 1,2
      diaminobenzene, resorcinol, 4-hydroxybenzenesulfonic acid, and a combination of
      two polymers, 1,2-diaminobenzene and resorcinol. An inner membrane constructed
      from cellulose acetate (CA) was deposited prior to immobilization with
      glutaraldehyde. The analytical characteristics of the microelectrodes, including
      optimization of immobilization procedures, calibration curves, pH response
      curves, stability, and selectivity toward possible electroactive compounds found
      in the brain extracellular fluid, were determined. The best microelectrodes were
      prepared by cross-linking the enzymes with glutaraldehyde on top of the inner CA
      membrane. The responses are linear in the concentration range 5.0 x 10(-7)-1.0 x
      10(-4) M Ch and 5.0 x 10(-7)-9.3 x 10(-5) M Ach. The time to reach 95% steady
      state current was 15-20 s. The CA-coated Ch microelectrodes were useful for
      measurement of changes in Ch concentration in artificial brain extracellular
      fluid.

PMID- 8297013
TI  - Separation of the sticky peptides from membrane proteins by high-performance
      liquid chromatography in a normal-phase system.
AB  - The amphiphilic peptides obtained upon cleavage of membrane proteins, including
      numerous receptors, are recalcitrant to most separation techniques as a
      consequence of their limited solubility and tendency to aggregate and adsorb to
      surfaces. This paper describes HPLC systems that can separate these "sticky"
      peptides on silica and aminopropyl-modified silica columns with a mobile phase
      consisting of a mixture of chloroform/methanol/isopropylamine. The protocols
      developed have been applied to synthetic M1 and M2 peptides, which constitute
      part of the transmembrane domain of glutamate-gated ion-channel proteins. Four of
      these M1 and M2 peptides were separated from minor synthetic impurities, and a 23
      mer was baseline separated from a 28-mer. The HPLC procedures have also led to
      purification of the 10 peptides resulting from cyanogen bromide cleavage of
      bacteriorhodopsin, peptides which have so far eluded HPLC separation despite
      numerous attempts. These HPLC protocols have been used to purify peptides ranging
      from 4 to 50 amino acids in high yield while the columns continued to resolve
      sharp peaks after more than 100 separation runs over a 6-month period. These new
      HPLC systems offer an efficient method for the isolation and analysis of this
      important albeit troublesome class of peptides.

PMID- 8297014
TI  - Assay of preproenkephalin A processing enzymes in human lumbar cerebrospinal
      fluid.
AB  - Vmax and Km measurements have been obtained for endogenous peptidases that are
      important for methionine enkephalin (ME) homeostasis in humans. Those peptidases
      in human lumbar cerebrospinal fluid (CSF) act upon several synthetic biologically
      significant peptides that are also contained within the preproenkephalin Ahuman,1
      267 molecule. The amount of endogenous methionine enkephalin-like
      immunoreactivity (ME-li) in human lumbar CSF is 74.1 +/- 5.7 fmol ME-li/ml CSF (n
      = 56; mean +/- SE). The kinetic parameters of the various enzymes that inactivate
      exogenous, synthetic methionine enkephalin (ME, YGGFM) and that also produce ME
      from two different portions of the preproenkephalin Ahuman,1-267 precursor
      molecule were determined. The enzyme that inactivates synthetic ME to FM, and
      that correlates to the rate of decrease of ME, has a Vmax = 560 +/- 43.3
      nmol/ml/min and a Km = 4514 +/- 373 microM (n = 56; mean +/- SE).
      Preproenkephalin Ahuman,186-193 (PA = YGGFMRGL) was added to CSF samples to
      characterize those processing and converting enzymes that produce the ME
      pentapeptide. Vmax, as measured by the rate of the decrease of PA to produce
      YGGFMR, was 0.192 +/- 0.038 nmol/ml/min and a Km of 513 +/- 121 microM (n = 10;
      mean +/- SE). Similarly, a bovine analog to preproenkephalin Ahuman,128-140
      (PPEhuman, GSEILAKRYGGFM; PPEbovine,125-137, GGEVLGKRYGGFM) was used to
      characterize that enzyme system that produces ME from an N-terminally extended ME
      peptide. That endopeptidase had a Vmax of 0.120 +/- 0.048 nmol/ml/min with a Km
      of 734 +/- 296 microM (n = 10). Those endogenous enzymes in human CSF may relate
      to the proopiomelanocortin convertase enzymes that contain the subtilisin-like
      catalytic domain.

PMID- 8297015
TI  - A rapid method for quantitation of oligodeoxynucleotide phosphorothioates in
      biological fluids and tissues.
AB  - A sensitive and simple method for the quantitation of oligonucleotide
      phosphorothioates in biological fluids and tissues is described. This method is
      based on the extraction of the oligonucleotide from the biological fluids and
      tissues and immobilization on a nylon membrane. The membrane-bound
      oligodeoxynucleotide phosphorothioate is then hybridized with labeled
      complementary oligonucleotide and exposed to X-ray film. The data on the film can
      be scanned and used to create a standard curve. The sensitivity of detection by
      the method described here will be useful to monitor the pharmacokinetics of
      oligonucleotides in bodily fluids and distribution in various tissues. The
      results indicate that the method is rapid and allows handling of a large number
      of samples at the same time.

PMID- 8297016
TI  - New spectrophotometric assay for polyphenol oxidase activity.
AB  - We describe a convenient and sensitive assay of polyphenol oxidase (PPO, EC
      1.14.18.1) consisting of spectrophotometry at 300 nm based on the stoichiometric
      reaction of cysteine with o-quinones produced during the enzymatic oxidation of
      phenols. The adduct formed exhibited spectral properties different from those of
      the parent phenol. PPO activities extracted from apple, pear, and mushroom were
      assayed. The assay cannot be used with hydroxycinnamoyl derivatives since the
      cysteinyl adduct compounds exhibited spectral properties similar to those of
      their parent phenolic substrates. However, the cysteine-coupled method presents
      several advantages over the measurement of oxygen uptake by polarography or the
      direct estimation of o-quinone by spectrophotometry. The duration of the linear
      period was increased, allowing a better estimation of its value. The zone of
      proportionality between rates and enzyme quantities was enlarged. The difference
      in molar extinction coefficients between adduct and phenol at 300 nm ranged
      between 2000 and 2800 M-1.cm-1, i.e., two times higher than those of the
      corresponding o-quinones. Therefore, this assay improves the sensitivity of
      polyphenol oxidase detection over that of the direct spectrophotometric assay of
      quinone formation.

PMID- 8297017
TI  - Determination of bound sulfur in serum by gas dialysis/high-performance liquid
      chromatography.
AB  - A sensitive high-performance liquid chromatography (HPLC) method has been
      developed for the determination of bound sulfur in mammalian serum. In this work,
      bound sulfur is defined as divalent sulfur that is easily liberated as sulfide by
      reduction with dithiothreitol. Released sulfide was treated by flow gas dialysis
      and converted into a fluorescent derivative, thionine, through the reaction with
      p-phenylenediamine and ferric ion. Thionine was then determined by HPLC using
      fluorometric detection. The calibration curve for bound sulfur is linear in the
      range from 0.1 to 10 microM, and the sensitivity of this method allows detection
      of less than 10 nM bound sulfur (0.5-ml sample). Recoveries of low-molecular
      weight and high-molecular-weight bound sulfur added to human serum at 1.0-5.0
      microM levels averaged between 94 and 101%. The proposed method was applied to
      the determination of bound sulfur in human and various animal sera. The mean
      concentration in normal human serum was 1.16 +/- 0.09 microM for males (n = 5)
      and 1.07 +/- 0.18 microM for females (n = 5). The mean concentrations ranged from
      1.55 to 6.18 microM in animal sera. The form of the sulfur bound in serum was
      also discussed.

PMID- 8297018
TI  - Pyridylethylation of cysteine residues in proteins.
AB  - A procedure is described for using an inert polyvinylidene difluoride type
      membrane (e.g., ProBlott) as a matrix for on-membrane gas-phase pyridylethylation
      and as a desalting (cleanup) support following the solution phase
      pyridylethylation of cysteine residues in proteins. As a desalting support for
      200 pmol of cardiotoxin, the membrane-derived sample gave a better recovery of
      phenylthiohydantoin (PTH)-amino acids during N-terminal sequencing compared to
      the sample obtained by rpHPLC. Using on-membrane gas-phase pyridylethylation,
      followed by replacement of glass-fiber filter disc and membrane washing/drying in
      vacuo, it was possible to eliminate the broad background peak that coeluted with
      PTH-Ala in the HPLC chromatogram completely. Using this modified procedure, there
      was no evidence of N-terminal alkylation of the amino-termini of proteins.

PMID- 8297019
TI  - Quantitative polymerase chain reaction with oligodeoxynucleotide ligation
      assay/enzyme-linked immunosorbent assay detection.
AB  - Quantitation of nucleic acids by the polymerase chain reaction (PCR) requires
      coamplification of a control nucleic acid, usually a variant of the sequence to
      be analyzed, which is added to the sample DNA and amplified in competition.
      Following PCR, amplified sample and control DNAs are separated by electrophoresis
      and quantitated, for example by measuring the radioactivity incorporated into the
      products during the PCR. The need for both electrophoretic separation and
      radioactive labeling has considerably impeded the use of PCR for routine
      purposes, e.g., in the clinical laboratory, which requires automatic processing
      of many samples in parallel. We describe here a quantitative PCR procedure which
      circumvents electrophoretic separation and detection by radioactivity. It uses a
      point mutated version of the sample DNA as an internal control. After competitive
      PCR, amplified sample and control DNA are distinguished by an
      oligodeoxynucleotide ligation assay (OLA) (Landegren et al., Science 241, 1077
      1080, 1988) using two oligodeoxynucleotides, one carrying a biotin-group at the
      5'-end and another one with either a digoxigenin (specific for sample DNA) or
      fluorescein moiety (specific for control DNA), respectively, incorporated close
      to the 3'-end. Biotinylated oligodeoxynucleotides, educts as well as products of
      the ligation reaction, are immobilized on avidin-coated microtiter plates.
      Quantitation of digoxigenin and fluorescein-labeled oligodeoxynucleotide ligation
      products is achieved by an enzyme-linked immunosorbent assay. This method is very
      well suited for fast automated or semiautomated PCR.

PMID- 8297020
TI  - Simultaneous measurement of two cations with the fluorescent dye indo-1.
AB  - The fluorescent chelator Indo-1 can simultaneously provide information about two
      ions, such as Ca2+ and Ba2+, if spectra after binding can be distinguished from
      each other and from the ion-free dye. In the case of extracellular Ca2+ and Ba2+,
      the three spectra were found to be unique and independent, in the sense that no
      one of them could be approximated by any combination of the other two. Upon
      binding Ba2+, Indo-1 experienced a peak shift from 470 to 455 nm, whereas the
      peak for Ca(2+)-bound Indo-1 occurred at 405 nm. The computer could distinguish a
      contribution from Ba2-bound Indo-1 just as well when it was in a mixture
      containing contributions from free dye and Ca(2+)-bound Indo-1. The program used
      all the spectral data in a rapid noniterative calculation. It found the unique
      combination of Ca(2+)-bound, Ba(2+)-bound, and metal-free Indo-1 spectra which
      best matched the data. The spectral weighting factors which formed the best
      combination spectrum then corresponded to the relative concentrations of the dye
      in the three states. From these and the dissociation constants for Ca2+ and Ba2+,
      it was possible to calculate both [Ca2+] and [Ba2+] from a single data spectrum.
      The method was also applied to Mn2+, a metal which does not generate a unique
      spectrum, but which quenches Indo-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297021
TI  - A pH- and temperature-dependent cycling method that doubles the yield of
      microtubule protein.
AB  - This report describes a procedure for the isolation of microtubules (MTs) and
      microtubule-associated proteins from mammalian cultured cells and tissues. This
      method relies on the discovery that the solubility of brain tubulin is pH
      sensitive. In this report, we examined tubulin solubility over a broad pH range
      and discovered that the amount of soluble tubulin increased by 240% as the pH was
      raised from 6.0 to 8.0. Quantitative immunoblotting revealed that there was an
      almost equal partitioning of tyrosinated and acetylated alpha-tubulin isotypes at
      the higher pH. These observations were incorporated into a new procedure for the
      purification of microtubule protein (MTP) from bovine brain and mouse B16
      cultured melanoma cells. Morphologically, and in terms of polypeptide
      composition, this MTP is indistinguishable from that prepared by a glycerol
      cycling method (21). Moreover, our new method of pH- and temperature-cycling
      yields almost twice as much MTP as that obtained by other cycling methods.

PMID- 8297022
TI  - Home test for cholesterol. Look, ma, no instrument.

PMID- 8297023
TI  - Improved chiral separation of basic compounds in capillary electrophoresis using
      beta-cyclodextrin and tetraalkylammonium reagents.
AB  - Approaches to improve resolution in chiral separation of several basic
      pharmaceutical compounds by capillary electrophoresis (CE) via a cyclodextrin
      (CD) inclusion complexation are described. Tetraalkylammonium reagents, including
      long-chain cationic surfactants and short-chain alkylammonium hydroxides, are
      examined for controlling the electroosmotic flow in order to improve resolution
      of the cationic enantiomers. In this regard, short-chain tetraalkylammonium
      cations (such as tetrabutylammonium and tetramethylammonium are more effective.
      First, the short-chain tetraalkylammonium cations can be used at much higher
      concentrations than the long-chain cationic surfactants, which form micelles in
      the few millimolar concentration range. As a result, a better capillary wall
      coverage is provided with the short-chain reagents, which leads to reduction or
      reversal of the direction of the electroosmotic flow at the acidic pH 2.5.
      Second, the short-chain tetraalkylammonium cations are relatively less
      hydrophobic and less likely to occupy the hydrophobic cavity of beta-CD than the
      long-chain cationic surfactants, leaving the enantioselective interaction sites
      more available for the analytes. The presence of these tetraalkylammonium cations
      was essential in many chiral separations that were reportedly not achieved by
      using the buffer electrolytes containing only the beta-CD as a chiral selector.
      In addition, a mechanism of chiral recognition by beta-CD for a group of
      stereoisomers is discussed.

PMID- 8297024
TI  - Automated process monitoring of monoclonal antibody production.
AB  - Antifibronectin, monoclonal antibody was monitored through 52 h of production.
      Samples were automatically drawn from a bioreactor into the injection valve of an
      HPLC system without prior sample preparation. The hybridoma cell line was
      nonadherent, so whole cells were injected directly onto the perfusable protein A
      affinity column. There was only a modest column back pressure (ca. 1700 psi at a
      linear flow rate of 1.5 cm/s) after over 75 injections over the 52-h experiment.
      These experiments demonstrate the utility of high-speed chromatography for rapid
      process monitoring.

PMID- 8297025
TI  - Specific flow injection sandwich binding assay for IgG using protein A and a
      fusion protein.
AB  - A sandwich-type flow-injection binding assay for quantitation of various IgG's
      was developed. The assay is based on the pseudoimmunological reaction between
      protein A from Staphylococcus aureus and immunoglobulin G from different species.
      Protein A immobilized on a solid support and a fusion protein of protein A and
      beta-galactosidase from Escherichia coli are used for detection. The fusion
      protein is produced with a temperature-inducible recombinant E. coli strain. A
      sandwich is formed by subsequent injection of IgG and fusion protein into the
      buffer stream flowing through the immobilized protein A column. The amount of
      enzyme activity bound is proportional to the amount of IgG bound and is measured
      by pumping a lactose solution as substrate for beta-galactosidase through the
      protein A column. Lactose is converted to glucose and galactose. The detector is
      an enzyme thermistor that measures the heat evolved in the enzymatic conversion
      of glucose by coimmobilized glucose oxidase and catalase. The assay takes 16 min
      at a flow rate of 0.6 mL min-1 with a lower detection limit of 33 pmol per
      injection of rabbit IgG. The precision of replicate measurements has a standard
      deviation of 4-5%, and the column can be used for more than 50 cycles.

PMID- 8297026
TI  - Use of synthetic peptides as tracer antigens in fluorescence polarization
      immunoassays of high molecular weight analytes.
AB  - This paper describes a homogeneous immunoassay based on fluorescence polarization
      that enables subnanomolar detection of high molecular weight analytes. A
      monoclonal antibody (Mab) to human chorionic gonadotrophin (hCG) was screened
      against a panel of 221 synthetic peptides using the method of Geysen et al.
      (Geysen, H. M.; et al. J. Immunol. Methods 1987, 102, 259-274. Geysen, H. M.; et
      al. J. Mol. Immunol. 1986, 23, 709-715). One of these peptides, which was located
      near the C-terminus of the hCG beta chain, bound to the Mab with high affinity.
      It was labeled with tetramethylrhodamine (TMR) and used as the tracer antigen in
      a competitive fluorescence polarization immunoassay (FPIA) for hCG. The peptide
      TMR conjugate binds specifically to the anti-hCG Mab with an antigen-binding
      affinity (Ka) of 1.5 x 10(7) M-1 at 6 degrees C. Its fluorescence intensity was
      enhanced by approximately 20% upon binding as a result of a prolonged excited
      state lifetime. In a typical embodiment, hCG was determined at a level of 1 x 10(
      9) M (95% confidence limit)--a 100-fold improvement over similar systems reported
      in the literature. This is mainly attributed to the large difference in
      hydrodynamic volume between the tracer and the antibody, which resulted in large
      changes in polarization of the peptide tracer upon binding. Issues related to
      sensitivity, specificity, and reversibility were also investigated. This method
      is believed to be of significant importance to rapid and economical measurements
      of high molecular weight antigens of clinical interest.

PMID- 8297027
TI  - Osteoblast attachment monitored with a quartz crystal microbalance.
AB  - A quartz crystal microbalance is used in aqueous solutions to monitor the rate of
      attachment of osteoblasts, bone-forming cells, to the surface of the crystal.
      Changes in resonant frequency of the crystal are measured for various surface
      coverages by osteoblasts. Crystal surface coverages are determined by digital
      image processing of scanning electron micrographs. A linear relationship is
      established between the surface coverages and the changes in resonant frequency
      of the crystal. The osteoblasts are observed to behave viscoelastically. Hence,
      the Sauerbrey equation can not be used to describe the relationship between the
      change in mass of osteoblasts on the surface and the change in resonant frequency
      of the crystal. Apparent viscosities at 5.0 MHz are also determined for
      osteoblasts.

PMID- 8297028
TI  - Determination of arsenic(III) and selenium(IV) using an on-line anodic stripping
      voltammetry flow cell with detection by inductively coupled plasma atomic
      emission spectrometry and inductively coupled plasma mass spectrometry.
AB  - An on-line anodic stripping voltammetry (ASV) flow system, interfaced with
      inductively coupled plasma atomic emission spectrometry (ICP-AES) and inductively
      coupled plasma mass spectrometry (ICPMS) detectors, has been used for
      determination of arsenic(III) and selenium(IV) and for elimination of polyatomic
      interferences which arise from chloride in sample matrices. Details of the
      working electrode preparation are discussed. Arsenic signals in ICP-AES were
      enhanced by as much as 10 times through preconcentration of sample volumes up to
      5 mL. Using ICP-AES detection, recoveries for analyte spikes in 1:10 diluted
      urine were 102% for As(III) (matrix-matched standards) and 91% for Se(IV)
      (standards in electrolyte). Using ICPMS detection, determination of certified
      Se(IV) and Se(IV) spikes in diluted NIST SRM 2670 elevated urine gave recoveries
      of 92-103%, while recoveries of As(III) spikes in diluted NIST SRM 2670 urine
      ranged from 94 to 113%. High levels of chloride matrix exhibited little effect on
      the arsenic signal with ICP-AES or ICPMS detection. Elimination of the polyatomic
      interference ArCl+ in ICPMS was very efficient for diluted NIST SRM 2670 urine
      and for a synthetic matrix of 1000 micrograms/mL chloride.

PMID- 8297029
TI  - Surfactant-modified graphite surfaces in biological analysis: ionic strength and
      ion charge effects.
AB  - Previous work with rough pyrolytic graphite and glassy carbon electrodes
      demonstrated that surfactant assembly at these two structurally and chemically
      different surfaces was similar, with surfactants adsorbing head on. Improvement
      in response of biological molecules was attributed to the formation of a dynamic,
      renewable surface. Furthermore, surfactants provided a favorable hydrophobic
      hydrophilic environment for the response of selected catechols. Surfactants could
      also be used to control selectivity if needed. In this work ionic strength and
      cation charge effects on response of catechols in surfactant solutions are
      investigated. The results illustrate the relative importance of electrostatic and
      hydrophobic interactions at graphite to the response of probes with combined
      hydrophobic and hydrophilic properties. Furthermore, the results show that
      although catechol-surface interactions are significantly affected by ionic
      strength and electrolyte charge, surfactant-surface and surfactant-probe
      interactions are not significantly affected, indicating that surfactants serve as
      an effective ionic buffer. The results presented here indicate that surfactant
      assembly at the surface is best at low ionic strength. These results also verify
      the importance of a favorable hydrophobic and hydrophilic environment to catechol
      response which can be provided by the surfactants when needed.

PMID- 8297030
TI  - Capillary electroseparations of some di-, tri-, and tetrapeptides and enkephalin
      related peptides.
AB  - Electrophoretic mobilities and capacity factors for short peptides were
      determined in micellar electrokinetic systems (MEKC) using UV detection at 210
      nm. On the basis of determined capacity ratios, taurodeoxycholic acid was found
      to be a selective micellar agent for peptides. Structural features other than
      hydrophobicity were found to be decisive for the distribution of the peptides to
      the micellar phase. Basic peptides of enkephalin-type containing arginine were
      more highly distributed to the micelles than others, indicating the importance of
      electrostatic forces in the distribution mechanism. In systems with
      polyacrylamide-coated capillaries, the micellar velocity toward the anode is
      larger than the electroosmosis, and conditions permitting splitting of a series
      of related peptides, i.e., some peptides migrating with the micelles and others
      toward the cathode resulting in infinite selectivities, were developed.
      Separation by micellar electrokinetic chromatography is demonstrated to be a
      suitable alternative for peptides that are difficult to separate by capillary
      zone electrophoresis.

PMID- 8297031
TI  - High-precision liquid chromatography-combustion isotope ratio mass spectrometry.
AB  - Online liquid chromatography-combustion high-precision carbon isotope ratio mass
      spectrometry (LCC-IRMS) is demonstrated for the first time with a direct
      interface to the liquid source. The interface is based on a continuously coated
      moving wire which facilitates reproducible solvent removal and analyte
      combustion, followed by drying of the CO2 and admission to the mass spectrometer.
      Routine precision and accuracy for compounds analyzed with the interface in the
      flow injection mode is about delta 13CPDB = 0.5/1000 over the range -28 < delta
      13CPDB < 83. Precision in the liquid chromatography mode is routinely
      approximately 1/1000 and is limited by sample size. This system expands the range
      of online compound-specific isotope ratio analysis (CSIA) to thermally labile and
      nonvolatile compounds.

PMID- 8297032
TI  - Development of techniques for the isolation of iron from biological material for
      measurement of isotope ratios by fast atom bombardment mass spectrometry.
AB  - Stable isotopes have gained prominence in nutrition and trace element research.
      Fast atom bombardment mass spectrometry (FAB-MS) measurement of iron isotope
      ratios has an accuracy of > or equal to 99.7% with the stable isotopes (54)Fe,
      (56)Fe, and (58)Fe with relative standard deviations (RSDs) of < or equal to
      0.9%. The isolation of iron from biological matrices can be accomplished in 4 h
      with almost total removal of isobaric interferences caused by (39)KOH, (39)K.H2O,
      (40)CaOH, and/or (40)Ca.H2O. FAB-MS isotope enrichment measurements from this
      method compare favorably to predicted absorption/enrichment levels.

PMID- 8297033
TI  - Glucose electrodes based on cross-linked [Os(bpy)2Cl]+/2+ complexed poly(1
      vinylimidazole) films.
AB  - Enzyme electrodes based on a redox hydrogel formed upon complexing water-soluble
      poly(1-vinylimidazole) (PVI) with [Os(bpy)2Cl]+ and cross-linked with water
      soluble poly(ethylene glycol) diglycidyl ether (molecular weight 400, peg 400)
      are described. The properties of the electrodes depended on their polymers'
      osmium content, the extent of cross-linking, the pH, and the ionic strength in
      which they were used. The redox hydrogels' electron diffusion coefficients (De)
      increased with osmium content of their polymers. The De values were 1.5 x 10(-8),
      1.3 x 10(-8), and 4.3 x 10(-9) cm2/s for PVI3-Os, PVI5-Os, and PVI10-Os,
      respectively, the subscripts indicating the number of monomer units per osmium
      redox center. De decreased with increasing ionic strength and increased upon
      protonation of the polymer. In glucose electrodes, made by incorporating into
      their films glucose oxidase (GOX) through covalent bonding in the cross-linking
      step, glucose was electrooxidized at > 150 mV (SCE). The characteristics of these
      electrodes depended on the GOX concentration, film thickness, O2 concentration,
      pH, NaCl concentration, and electrode potential. The steady-state glucose
      electrooxidation currents were independent of the polymers' osmium content in the
      studied (3-10 monomer units per osmium center) range. Electrodes containing 39%
      GOX reached steady-state glucose electrooxidation current densities of 400
      microA/cm2 and, when made with thick gel films, were selective for glucose in the
      presence of physiological concentrations of ascorbate and acetaminophen.

PMID- 8297034
TI  - Active chemical background and noise reduction in capillary electrophoresis/ion
      trap mass spectrometry.

PMID- 8297035
TI  - Factors affecting electrospray ionization of effluents containing trifluoroacetic
      acid for high-performance liquid chromatography/mass spectrometry.

PMID- 8297036
TI  - Simultaneous determination of ammonia nitrogen and L-glutamine in bioreactor
      media using flow injection.
AB  - A novel split stream flow injection (FI) system suitable for the simultaneous
      determination of L-glutamine and ammonia nitrogen (ammonia-N) in cell culture
      media is described. Potentiometric detection of ammonia-N in one portion of the
      manifold is achieved using a commercial ammonia gas-sensing electrode fitted with
      a wall-jet cap. L-Glutamine is quantified in the other part of the split sample
      by potentiometric detection of ammonium ions (by an ammonium-selective polymer
      membrane electrode), liberated from the hydrolysis of glutamine after the sample
      flows through a glass bead reactor containing immobilized glutaminase. Endogenous
      ammonia-N and potassium ions that would normally interfere with the glutamine
      measurement are removed upstream using a unique tubular cation-exchange unit.
      Using 50 microliters sample volumes and mixed solutions of ammonium chloride and
      L-glutamine in Iscove's Modified Dulbecco's Medium to calibrate the FI measuring
      system, values for ammonia-N and L-glutamine determined for 22 media samples
      obtained from a bioreactor growing retroviral producer cells correlate well with
      those measured with commercial, manual enzymic-spectrophotometric assay kits.

PMID- 8297037
TI  - The development of the neural crest in amphibians.
AB  - Our review deals with the development of the neural crest (NC) in amphibians. We
      will consider relevant aspects of evolution, ontogeny, migration and
      differentiation, and investigate principal problems such as the regulation of NC
      cell determination, pathway selection and destination recognition. Earlier data
      and more recent findings will be presented. The NC probably evolved about 440
      million years ago from the anlagen of epidermal nerve plexuses in protochordates.
      In urodele amphibians, the prospective NC is already present in the early
      gastrula as a narrow band of ectodermal cells between the prospective epidermis
      and the prospective neural plate. The NC proper develops later from the apices of
      the neural folds and forms, after neural fold fusion, a transient cellular ridge
      on the dorsal surface of the neural tube. NC cells migrate extensively into
      various body regions and give rise to a wide variety of derivatives including the
      mesenchymal elements of the skull, the neural and glial precursors of the
      peripheral nervous system and the pigment cells. NC cell migration is stimulated
      by components of the extracellular matrix (ECM) and may conveniently be analyzed
      in the system of wild-type (dark) and white mutant axolotl embryos. Skeletal
      elements of the head derive from cranial NC cells following an interaction with
      pharyngeal endoderm. Other derivatives of the NC are the ganglia of the
      peripheral nervous system in the head (sensory ganglia; mostly mixed origin with
      placodal material) and trunk (spinal, sympathetic and enteric ganglia). Pigment
      cells also derive from the NC and become arranged into uniform or banded pigment
      patterns.

PMID- 8297038
TI  - Mammalian neural crest and neural crest derivatives.
AB  - In the mammalian embryonic trunk, neural crest cells emigrate from the closed
      neural tube in a cranio-caudal sequences and appear to have similar migration
      pathways and derivatives to those of avian embryos. In the cranial region,
      however, there are mammalian-specific features, which are related to the
      mammalian-specific pattern of cranial neurulation. Midbrain and rostral hindbrain
      neural crest cells emigrate from widely open neural folds; caudal hindbrain crest
      emigrates in a caudo-rostral sequence, following the sequence of neural tube
      closure in this region. The forebrain is also a source of neural crest cells at
      early stages of neurulation; both forebrain and midbrain crest cells contribute
      to the frontonasal mesenchyme, although their relative contributions have not
      been analysed. Few studies have provided direct information about mammalian
      neural crest cell derivatives. Studies on the effects of retinoid excess on
      craniofacial development provide indirect evidence that mammalian cranial neural
      crest, like that of avian embryos, includes two populations whose differentiated
      phenotype and morphological tissue structure are determined prior to emigration.
      Retinoid-induced shortening of the preotic hindbrain leads to abnormal migration
      pathways of the neural crest cells that normally migrate into the mandibular arch
      to form Meckel's cartilage, so that an ectopic Meckel's cartilage-like structure
      forms in the maxillary region of the face. Slow descent of the heart in retinoid
      exposed embryos enables the "wrong" crest cell population to populate the wall of
      the truncus arteriosus. These observations correlate well with observations of
      retinoid-induced craniofacial and heart abnormalities in human infants.

PMID- 8297039
TI  - The functional organization of somatosensory cortex in primates.
AB  - Our understanding of the functional organization of somatosensory cortex and
      thalamus in primates and other mammals has greatly increased over the last few
      years. It is now clear that higher primates have four strip-like representations
      of skin and muscle receptors corresponding to areas 3 a, 3b, 1 and 2 of anterior
      parietal cortex. Areas 3b and 1 receive cutaneous information from the
      ventroposterior nucleus, while a ventroposterior superior nucleus provides areas
      3a and 2 with information from muscle receptors. Area 3b is the homolog of S-I in
      prosimians and non-primates and it provides most of the activating cutaneous
      inputs to areas 1 and 2. Most of the further processing that allows tactile
      recognition of objects involves somatosensory areas of the lateral sulcus, where
      both S-II and the parietal ventral area (PV) receive activating inputs from areas
      3a, 3b, 1 and 2. S-II also projects to PV and to a parietal rostral area where
      further connections with the amygdala and hippocampus may occur to allow the
      formation of tactile memories. Areas of anterior parietal cortex also project to
      posterior parietal cortex, where regions of cortex are largely somatosensory, but
      the functional subdivisions remain uncertain. All of the somatosensory fields
      have access to motor areas of the frontal lobe, but the magnitude and targets of
      the projections differ.

PMID- 8297040
TI  - [A human representation of humans? Changes in human representation in anatomy].
AB  - When during the last three decades of the 19th century German clinical medicine
      was established as a natural science anatomy e.g. was referred to as a model on
      this way. At that time this discipline, however, was delved into Richtungskampfe
      between evolutionary morphology on the one side and physiological and clinical
      orientated anatomy on the other, comprising a discussion on the
      Wissenschaftlichkeit of the different directions. In the end anatomy evolved as a
      medical discipline leaving evolutionary morphology to the zoologists.
      Concomitantly with this change in the self-conception of the discipline as a
      natural science anatomy was charged with the imprinting of the prospective
      physician and his picture of the human being. This respective picture is analysed
      in the anatomical illustration from Vesalius up to nowadays considering the unity
      of art and anatomy in the visual media as well as in its disjunction. In this
      context the dominance of science on art in the service of anatomy is discussed
      with special reference to the neoclassical influence on further development. The
      latter is characterized by an increasing abstraction and diagrammatic
      representation of the human figure referring to man as a reparable
      electrochemical machine without mystery. This corresponds to a clinical medicine
      comprehending as a reparative and mechanical profession. The restoration of a
      human picture of the human being may be achieved by an anatomy directed to life
      and an art extended to an anthropological conception.

PMID- 8297041
TI  - Unusual branching and course of the testicular artery.
AB  - In a Turkish male, the right testicular artery was found to originate from the
      aorta at nearly the same level as and anterior to the renal artery. This
      testicular artery was seen to give off the inferior phrenic and superior
      suprarenal arteries. During its course the artery was posterior to the inferior
      vena cava. In addition to the above mentioned characteristics, the artery arose 5
      mm below the renal vein and, after ascending to the superior border of the renal
      vein, arched over and descended in front of it to continue along its downwards
      course. This case implies that the lateral mesonephric arteries form anastomoses
      and that different arteries may interfere with each other's development. Another
      significant fact in this case is that the testicular artery crossed over the
      renal vein and descended anterior to it; a condition which may cause pathological
      disturbances.

PMID- 8297042
TI  - [Areas of contact in human humero-ulnar joints as a function of pressure, their
      connection through subchondral mineralization and joint surface morphology of the
      incisura trochlearis].
AB  - Evaluation of the stress distribution in joints can be obtained directly from
      contact areas and pressure forces, and also indirectly from the functional
      adaptation of the connective tissues. Therefore 8 human humero-ulnar joints,
      fixed in formalin, were examined for size and position of contact areas
      (polyether casting/Vidas image analyser) and their dependence upon the joint
      forces (Zwick material testing machine). The distribution of subchondral
      mineralisation was assessed, using CT osteoabsorptiometry. Depending on the joint
      force, the contact areas increase from about 10% of the total surface (20 N) to
      approximately 60% (1280 N). With weak forces they are localised ventrally and
      dorsally in the joint, with more powerful forces they run together centrally.
      With a divided articular surface they join at about 160-640 N, with a continuous
      surface, at about 40-80 N. Divided joint surfaces show a bicentric mineralisation
      pattern of the subchondral bone with ventral and dorsal maxima. Continuous
      surfaces, on the other hand, usually show central maxima. Both the mineralisation
      pattern and the position of the contact areas suggest a physiological incongruity
      of the humero-ulnar joint surfaces, which vanishes with increasing pressure due
      to viscoelastic deformation of articular cartilage and subchondral bone. More
      marked incongruity is postulated for the divided surfaces than for the others.
      The consequent peripheral transmission of pressure seems to involve a functional
      principle, which, present in several human joints, leads to both optimal
      distribution of the stress and better nutrition of the articular cartilage.

PMID- 8297043
TI  - A special form of hyperostosis frontalis interna.
AB  - The article describes a very severe case of hyperostosis of the frontal bone and
      discusses its possible differential diagnosis. What makes this case special is
      the fact that the osseous changes include all 3 layers of the bone.
      Macroscopically the lesion resembles an osteoma as described by Burkhardt (1970)
      and v. Eiselsberg (1906). The histological examination lead to the final
      diagnosis of hyperostosis frontalis interna. One must note that there were
      certain effects caused by a metastasis of a lobular carcinoma of the breast which
      influenced the osseous changes from the outer surface. The rough, spicula-like
      structure in the centre of the frontal squama should be put down to tumour
      erosion. The peripheral areas of the hyperostosis, however, still exhibit the
      original smoother texture of the disease. The final diagnosis in this unusual and
      possibly unique case was an intense hyperostosis frontalis interna with secondary
      changes due to the metastases of a lobular carcinoma of the breast.

PMID- 8297044
TI  - Immunohistochemical localisation of the 90, 70 and 25 kDa heat shock proteins in
      control and caffeine treated rat embryos.
AB  - Human and animal experimental data demonstrate that in utero exposure to caffeine
      results in intrauterine growth retardation and long-term behavioural and
      reproductive effects. We have suggested that the disruption of normal
      transcription and translation associated with the initiation of the heat shock
      response may be a possible mechanism of action of caffeine. This hypothesis was
      investigated using immunohistochemistry to determine whether an acute (3 h) dose
      of 30 mg/kg caffeine alters the distribution of hsp 90, 70 and 25 in 10.5-12.5
      g.d. rat embryos. In the control embryos hsps 90 and 70 were distributed
      throughout the embryo with no areas of specific accumulation. Hsp 25 was
      localised to the developing myocardium of 10.5, 11.5 and 12.5 g.d. embryos and
      the myotome of 11.5 and 12.5 g.d. embryos. The appearance of hsp 25 was
      correlated with the onset of muscle fibre differentiation and it is suggested
      that hsp 25 is associated with cytoskeletal proteins. Following dosing with
      caffeine no change in the distribution of staining for hsp 90, 70 and 25 was
      found. These results strongly suggest that caffeine's mechanism of action does
      not involve initiation of the heat shock response.

PMID- 8297045
TI  - Simultaneous bilateral occurrence of a M. extensor digiti medii and a M. extensor
      digitorum brevis.
AB  - For the first time, the simultaneous and bilateral occurrence of two variants of
      the extensors of the fingers, M. extensor digiti medii and M. extensor digitorum
      brevis, is reported. The extensor of the middle finger arises from the distal
      fourth of the radius and runs to the base of the proximal phalanx. The short
      extensor of the fingers arises from the metacarpal region and inserts into the
      dorsal aponeurosis. Both muscles are innervated by the R. profundus n. radialis.

PMID- 8297047
TI  - Conflicts of interest.

PMID- 8297046
TI  - The effect of androgen and estrogen on secretory epithelial cells and basal cells
      of the rat ventral prostate after long-term castration.
AB  - After long-term castration, rats were injected with cotton seed oil, testosterone
      and estradiol-17 beta-cypionate (CS, TC and EC). The height of the epithelial
      cells of the ventral prostates from the castrated rats increased after TC and EC
      injection. The secretory and basal cells formed two layers of epithelium, an
      inner layer near the lumen with pale nuclei and another layer with dark nuclei.
      These two layers could result from a reduction of secretory epithelial cells.
      Castration decreased the ratio of secretory cells to basal cells (S/B). TC
      injection increased the ratio of S/B because of the secretory epithelial cell
      growth. Longer dark cells may be transient cells, appearing during the
      differentiation of basal cells into secretory epithelial cells. A sheet branching
      off from the basal lamina was observed. Androgen may stimulate the synthesis of
      the lamina, but whether it induces the synthesis or turnover of the basal lamina
      has not been established. EC increased the ventral prostatic weight and secretory
      epithelial cell height and induced the appearance of crystalline granules.
      Increase in S/B ratio may result from an increase in the secretory epithelial
      cells, but not from basal cell multiplication due to squamous metaplasia. The
      ratio is significantly correlated to the weight of the ventral prostate, but not
      to the secretory epithelial cell height. Its value could indicate the
      multiplication of secretory epithelial cells, differentiation of basal cells into
      epithelial cells, or both. It is probable that basal cells do not change in
      number, but control the size of the rat ventral prostate in response to the
      hormone level.

PMID- 8297048
TI  - Orthopedic headgear forces.

PMID- 8297049
TI  - Case report BC: extraction decisions based on treatment responses.
AB  - We have all been into treatment and lost sight of the "plan" we were so familiar
      with at the treatment planning stage. Eighteen to 21 months into treatment, we
      are faced with extraction decisions or surgical planning that should have been
      addressed at 9 or 12 months. This case report illustrates a treatment plan with
      several variables that were dependent upon treatment responses. It also
      illustrates planning a gingival graft to increase the crown length of a first
      premolar after the canine was substituted as the lateral incisor.

PMID- 8297050
TI  - The effects of premolar-extraction: a long-term comparison of outcomes in "clear
      cut" extraction and nonextraction Class II patients.
AB  - Discriminant analysis was used to assess the anatomical basis of the
      extraction/nonextraction decision in 238 former Saint Louis University Class II
      edgewise patients. The resulting discriminant scores (based on six measures of
      protrusion and crowding) were used to divide this parent sample into three
      prognostic subgroups: clear-cut extraction, clear-cut nonextraction, and a
      borderline stratum containing both extraction and nonextraction patients. The
      "clear-cut" patients--those at the tails of the distribution--were then contacted
      and asked to return for follow-up records (cephalograms, models, clinical
      examination); in the end, 62 (33 extraction and 29 nonextraction) were recalled.
      The average post-treatment interval was about 15 years. Premolar extraction
      produced a significantly greater reduction in hard- and soft-tissue protrusion.
      During the post-treatment period, however, both groups underwent essentially the
      same change: decreased profile convexity and a pattern of dental change/relapse
      that was correlated with antero-posterior mandibular displacement. Because of
      their greater initial crowding and protrusion, the various effects summed to make
      the extraction patients significantly more protrusive at recall. Both treatments
      produced mesial mandibular displacement, extraction significantly more than
      nonextraction; however, at recall the two groups did not differ with respect to
      the signs and symptoms of dysfunction. The present findings, therefore, fail to
      support the common, influential belief that premolar extraction frequently causes
      "dished in" profiles, "distalized" mandibles, and, ultimately, craniomandibular
      dysfunction.

PMID- 8297051
TI  - Correlation and prediction: interpreting the significance of r.
AB  - Given the growing popularity of cephalometric programs for the personal computer,
      it is once again necessary for the specialty to confront the problem of
      prediction accuracy. The strength of the relationships upon which a prediction
      scheme is based is often assessed by means of the coefficient of linear
      correlation, r. Although it is common to judge the practical significance of a
      relationship by squaring the correlation coefficient, the present paper argues
      that the index of forecasting efficiency, the percentage reduction in error, is
      not only the more appropriate index, but also one that is easy to infer directly
      from r.

PMID- 8297052
TI  - Craniofacial morphology of adolescent mandibular prognathism.
AB  - Morphological features of the craniofacial complex during orthopedic chin cup
      therapy were investigated in growing patients with mandibular prognathism.
      Lateral cephalograms of 30 subjects (15 boys and 15 girls, mean age: 9.04 +/-
      1.29 years), taken at four different stages during treatment, were analyzed for
      14 measurements. These measured values were standardized by use of Japanese
      controls and then evaluated to investigate longitudinal changes in the
      craniofacial morphology at the four different stages. Further, factor analysis
      was used to compare factors describing the craniofacial morphology for the
      initial and final stages. Dimensional changes of the mandible were not easily
      produced even if orthopedic treatment was conducted, whereas the maxilla
      exhibited a tendency to approach the normal range of the controls. Positional
      changes of the complex, the backward and downward repositioning of the mandible
      in particular, played an important role in altering a profile from prognathic
      before treatment to orthognathic at the end of treatment. Craniofacial morphology
      was similar pretreatment and posttreatment, although the orthognathic factor
      became more prominent when associated with positional changes of the mandible at
      the end of treatment.

PMID- 8297053
TI  - Associations between severity of dentofacial deformity and motivation for
      orthodontic-orthognathic surgery treatment.
AB  - The successful outcome of orthognathic surgery is related to patient satisfaction
      and motivation. The aim of this retrospective study was to analyze the
      association between 1) severity of dentofacial deformity derived from
      cephalometric measures and 2) patient motivation for treatment. The initial
      cephalograms of 142 patients aged 16 years or older from the Dentofacial Program
      of the University of Michigan were traced and digitized. Inclusion criteria were
      established by assigning ANB 4 degrees to 15 degrees to define severe skeletal
      Class II (n = 65) and ANB - 15 degrees to -4 degrees to define severe skeletal
      Class III (n = 20). Motivation for orthodontics and surgery was derived from
      clinician administered forms scaled 1-10 with Low (1-5) and High (8-10). The
      cephalometric measure ANB was significant (p = 0.02) for high/low motivation for
      orthodontic treatment using Student's t test. No other cephalometric measures
      were significant for high/low motivation for orthodontics or surgery using
      Student's t test. Class II patients were significantly (p = 0.014) more motivated
      than Class III patients for orthodontic treatment. No significant difference was
      found for motivation for surgery between skeletal Class II and skeletal Class III
      patients. Patients with severe sagittal Class II deformities had higher
      motivation for orthodontics than surgery. The cephalometric measure, ANB,
      defining severe skeletal Class II and Class III patients did predict motivation
      level for orthodontics. None of the other 18 cephalometric measures were
      predictive of patient motivation for either orthodontics or surgery.

PMID- 8297054
TI  - Anabolic steroids and craniofacial growth in the rat.
AB  - Anabolic steroids are misused by adolescents as well as adults to increase muscle
      and improve appearance and athletic performance. Since these substances strongly
      enhance protein synthesis, it was speculated that craniofacial changes in bone
      size and, perhaps, skeletodental relationships might also occur. Eighty rat pups
      were divided into three groups: (1) sham-treated controls, (2) a low-dose group
      (1 mg/kg/wk nandrolone phenpropionate), and (3) a high-dose group (10 mg/kg/wk).
      The high-dose regimen more closely mimics dosages used by abusers. Steroid
      therapy significantly increased all measures of the craniofacial complex (k = 20)
      -on the order of 3.5%-except some precocious calvarial dimensions. Importantly,
      significant alterations also occurred in facial morphology. The low-dose group
      exhibited proportionate increases in most craniofacial dimensions, but the high
      dose produced overt shape changes, notably a maxillomandibular, anteroposterior
      jaw discrepancy due to maxillary excess. In sum, this anabolic steroid
      significantly altered facial growth in this animal model; by extension, steroid
      abuse by adolescent humans may produce discernible changes in their craniofacial
      complexes.

PMID- 8297055
TI  - Thermal effects associated with the Nd/YAG dental laser.
AB  - The heat produced at the dentinal pulpal wall opposite the irradiation site was
      measured during etching of dental enamel with an Nd:YAG laser in preparation for
      direct bonding of orthodontic appliances. Forty extracted human teeth were
      randomly divided into four groups of 10 teeth. Within each group, the buccal
      surfaces of 5 teeth and the lingual surfaces of the other 5 teeth were laser
      treated for 12 sec. Irradiation was performed with a commercial Nd:YAG laser at
      the power settings of 80mJ, 1W, 2W and 3W. Prior to irradiation, an occlusal
      access preparation was made into the pulp in order to facilitate the placement of
      a thermocouple for measurement of temperature changes at the dentinal pulpal wall
      opposite the irradiation site. The thermocouple was held against the dentinal
      pulpal wall and the resulting temperature changes were recorded. Heating effects
      at the dentinal pulpal wall on both buccal and lingual surfaces showed an
      increase in heat as a function of the increase in power output from the laser
      unit (p < 0.01). The temperatures measured at power levels 1-3W appeared to be of
      sufficient magnitude to cause at least localized pulpal inflammation and possible
      irreversible damage to the pulp tissue immediately opposite the site of laser
      irradiation.

PMID- 8297056
TI  - On tooth movement.
AB  - Current concepts of clinical orthodontic tooth movement are misleading.
      Traditionally, these have been described as dependent on force levels and being
      tipping/bodily in nature. The following is a reevaluation of the relationships
      between tooth movement and orthodontic mechanotherapy not usually considered when
      analyzing tooth movement clinically. It is our contention that confusion as to
      the biological response(s) to mechanical force is derived from in vivo
      orthodontic trials where conditions are undefined. This correlates with variable
      biological responses within the periodontium. Constantly changing moment to force
      ratios inherent to the dynamic load deflection rates of any system used to move a
      tooth cause changing tendencies for crown/root tipping. This implies that the
      accepted notion of static translatory tooth movement, although a useful didactic
      concept, is currently unattainable. In actuality, it has never been documented
      empirically using any conventional orthodontic appliance.

PMID- 8297057
TI  - The efficacy of psychological, educational, and behavioral treatment.
      Confirmation from meta-analysis.
AB  - Conventional reviews of research on the efficacy of psychological, educational,
      and behavioral treatments often find considerable variation in outcome among
      studies and, as a consequence, fail to reach firm conclusions about the overall
      effectiveness of the interventions in question. In contrast meta-analytic reviews
      show a strong, dramatic pattern of positive overall effects that cannot readily
      be explained as artifacts of meta-analytic technique or generalized placebo
      effects. Moreover, the effects are not so small that they can be dismissed as
      lacking practical or clinical significance. Although meta-analysis has
      limitations, there are good reasons to believe that its results are more credible
      than those of conventional reviews and to conclude that well-developed
      psychological, educational, and behavioral treatment is generally efficacious.

PMID- 8297058
TI  - APA-accredited predoctoral internships for doctoral training in psychology: 1993.

PMID- 8297059
TI  - APA-accredited doctoral programs in professional psychology: 1993.

PMID- 8297060
TI  - [Affective disorders in the child].
AB  - The existence of a depressive syndrome in childhood has been ignored or minimized
      until recently. In Geneva, a transversal study of the consulting population has
      confirmed the presence of a depressive syndrome, taking different clinical forms.
      It has also allowed us to describe an hypomaniac syndrome in children. An
      epidemiological study we did shows that a large proportion of adults suffering
      from cyclo-thymic disorders had consulted a doctor during their childhood or
      adolescence and that they already presented pathological signs related to this
      disorder. Moreover, children diagnosed as suffering from depressive and manic
      disorders showed similar symptoms, when adult, in an equally significant
      proportion.

PMID- 8297061
TI  - [Of glory and shame: a portrait of Oscar Wilde].
AB  - This study concerning the most controversial of British writers will surely evoke
      passionate reactions. Faced with the calibre and complexity of a figure such as
      Oscar Wilde, we concentrate our efforts on two lines of investigation event
      though we are aware that this will not satisfy all our readers. Firstly we look
      at the parallels between his principal work. The Picture of Dorian Gray, and his
      own tragic destiny. Many parallel themes can be found between the subject of the
      novel and the events of his own biography (particularly his relationship with an
      omnipresent mother in flagrant contrast to an absorbed and distant father). The
      second line of investigation looks at his problem of sexual identity. Oscar Wilde
      produced a work which described his own problems without any ambiguity. His
      homosexuality, his stage sense, his dandysm, as well as his taste for provocation
      and scandal are seen in the context of an unconditional relationship with a
      powerful mother which he attempted to find in his quest for substitutions love
      objects. It would seem that both, the relentless pursuit of his limits and the
      bearing of his secret fantasies, are not so much a reflection of a more or less
      verifiable reality but the product of as untiring elaboration of his fantasy
      life.

PMID- 8297062
TI  - [James Barrie or Peter Pan, the young boy who did not want to grow up].

PMID- 8297063
TI  - [Psychopathology and psychobiological origin of genius and creativity].

PMID- 8297064
TI  - [Germain Nouveau and psychiatry].

PMID- 8297065
TI  - Spontaneous corneal perforation with expulsive hemorrhage.
AB  - A case of unilateral spontaneous corneal perforation with expulsion of
      intraocular contents is reported in an old woman with corneal ulcer and hypopyon.
      Spontaneous corneal perforation with extrusion of intraocular contents is a
      disastrous and exceptional event that may occur in premature infants or in adults
      with severe ocular diseases. It is probable that, during the evolution of the
      corneal ulcer in this case, the organisms had caused necrosis of the cornea,
      culminating in a corneal perforation followed by a rapid decompression of the
      anterior chamber with a resultant expulsive hemorrhage. Glaucoma,
      arteriosclerosis, and hypertension could play a role in the genesis of the
      expulsive hemorrhage.

PMID- 8297066
TI  - Exuberant conjunctival pseudopolyposis in a patient with dermatomyositis.
AB  - Dermatomyositis is a disease of unknown cause, characterized by a diffuse
      inflammatory myopathy and skin changes consisting of heliotrope eruption,
      Gottron's papules, periungual telangiectasia with dystrophic cuticles, skin
      telangiectasia, and atrophy. Ocular involvement may consist of conjunctival
      edema, nystagmus, extraocular muscle imbalance (when associated with myasthenia
      gravis), iritis, cotton-wool spots, and optic atrophy. Conjunctival avascularity
      and membranous conjunctivitis also have been reported. We describe an unusual
      conjunctival finding with secondary corneal surface disturbances in a patient
      with dermatomyositis.

PMID- 8297067
TI  - Unilateral iridoschisis associated with syphilitic interstitial keratitis and
      glaucoma.
AB  - Iridoschisis is a rare condition that consists of the separation of the anterior
      mesodermic layer of the iris. It is associated with glaucoma in 50% of cases. The
      association of this disorder with luetic interstitial keratitis has been reported
      rarely. We report the case of a 58-year-old patient who had unilateral
      iridoschisis associated with glaucoma and syphilitic interstitial keratitis. We
      suggest that congenital syphilis might be considered as a cause of iridoschisis.

PMID- 8297068
TI  - Late visual recovery after intravenous methylprednisolone treatment of
      Purtscher's retinopathy.
AB  - A 25-year-old man involved in a minor traffic accident subsequently had a
      Purtscher's-type retinopathy and lost visual acuity (20/800). After treatment
      with intravenous methylprednisolone at a dose of 1 g/day, his visual acuity
      improved to 20/70 three days later and to 20/50 one week later. The exudates and
      hemorrhages gradually disappeared. However, a localized central scotoma and
      afferent pupillary defect still persisted. We review previous reports on the
      retinal pathophysiology of Purtscher retinopathy and discuss the potential
      benefit of treatment with high-dose intravenous corticosteroids.

PMID- 8297069
TI  - Tear film break-up time in contact lens wearers.
AB  - The increasing number of people who wear contact lenses for longer times
      comfortably while achieving good vision has been attributed to advances in
      plastics technology. Contact lenses are now worn by any adventurous ametropic
      patient whose vision is capable of optical improvement. This study was planned to
      observe the effect of gas-permeable and hard contact lenses with the following
      objectives: (1) to see whether there is any effect on the tear film break-up time
      with the different lenses; (2) to study the effect of the blink rate, if any; and
      (3) to examine the change in the width of the palpebral fissure. We found that
      only the type of lens affected the tear film break-up time and recommend that gas
      permeable lenses be preferred. Any change in the blink rate should be taken as an
      indication of a poor fit.

PMID- 8297070
TI  - Choroidal metastasis of cutaneous malignant melanoma treated by ruthenium-106
      plaque irradiation.
AB  - Symptomatic dissemination of cutaneous malignant melanoma to the choroid occurs
      rarely and is a grave prognostic factor. Therefore, choroidal tumors are treated
      only as a palliative measure. We present a case of cutaneous malignant melanoma
      with symptomatic metastasis in the choroid OD of a 38-year-old woman. We treated
      it using brachytherapy with a ruthenium-106 plaque. The tumor totally regressed
      with restoration of good vision. Twelve months of follow-up showed no systemic
      spread.

PMID- 8297071
TI  - A sporadic case of Lenz microphthalmia syndrome.
AB  - We present a sporadic case of colobomatous microphthalmia associated with
      multiple congenital anomalies. Our purpose is to add a new case of Lenz
      microphthalmia syndrome to the literature and to draw attention to the typical
      pattern of facial features of this disease.

PMID- 8297072
TI  - Leukemic relapse presenting as acute unilateral hypopyon in acute lymphocytic
      leukemia.
AB  - A 16-year-old girl with acute lymphocytic leukemia in hematologic remission and
      no evidence of active central nervous system disease had a unilateral hypopyon as
      her sole site of relapse. She underwent diagnostic paracentesis and was treated
      with topical corticosteroids, chemotherapy, and radiotherapy to the central
      nervous system. Ocular involvement of the iris and anterior chamber as the site
      of primary disease or a relapse is a rare event. The anterior chamber serves as a
      sanctuary for cancer cells, and treatment protocols, including better anterior
      chamber prophylaxis, are warranted.

PMID- 8297073
TI  - Optic disc coloboma associated with macular hole and retinal detachment.
AB  - A 15-year-old myopic girl had a retinal detachment associated with optic disc
      coloboma and a macular hole. The retinal detachment was treated successfully with
      vitrectomy, drainage of the subretinal fluid, and gas tamponade. The possibility
      of a macular hole should be investigated in myopic eyes with optic disc colobomas
      and retinal detachments. To the best of our knowledge, such a combination has not
      been described previously.

PMID- 8297074
TI  - Myelinated nerve fibers and refractory amblyopia: a case report.
AB  - We describe the case of a 3.5-year-old boy who had myelinated retinal nerve
      fibers and ipsilateral amblyopia refractory to occlusion therapy and simple
      myopic astigmatic correction. We suggest that myelinated nerve fibers may result
      in organic amblyopia with a resultant poor visual prognosis.

PMID- 8297075
TI  - Corneal changes in chondrodysplasia punctata syndrome.
AB  - A child with chondrodysplasia punctata syndrome is presented. In addition to the
      bilateral congenital cataracts that have been described previously in this
      syndrome, this child had bilateral corneal punctate erosions. These corneal
      abnormalities, which to the best of our knowledge have not been described in this
      syndrome before, persisted for at least three years.

PMID- 8297076
TI  - Sternal keloids: successful treatment employing surgery and adjunctive radiation.
AB  - Traditional treatment of keloids by surgery or surgery combined with other
      techniques has met with limited success. Successful treatment of sternal keloids
      by surgical excision and skin grafting, followed by radiation therapy is
      reported. Eleven patients, ranging in age from 14 to 66 years, were so treated.
      The groin was used as a donor site in all patients. Postoperative radiotherapy
      was administered to suture lines only, using three doses of 500 cGy each, such
      that 1,500 cGy was delivered within 7 to 14 days of surgery. The protocol was
      followed without variation in all patients. Follow-up ranged from 1 to 24 years.
      Only 1 patient demonstrated recurrence. Six patients received postoperative,
      episodic steroid injections for localized itching or nodule formation. None of
      these patients demonstrated recurrence of their keloids.

PMID- 8297077
TI  - The role of three-dimensional computed tomography in the evaluation of acute
      craniofacial trauma.
AB  - Three-dimensional computed tomographic (3-D CT) reformations together with their
      corresponding conventional axial two-dimensional (2-D) CT images of 20 patients
      with facial fractures were compared with 2-D CT alone to define their usefulness
      in the determination of facial skeletal fracture patterns. Nine surgeons with
      three different levels of experience and training evaluated the presence and
      spatial arrangement of fractures in all 2-D CT and 3-D CT scans. Comparisons were
      made between their evaluations of 2-D CT alone and 2-D CT plus 3-D CT scans.
      Statistical analysis with Friedman's test were performed. The addition of 3-D CT
      did not alter the interpretation of 2-D CT in 75% of evaluations. The number and
      accuracy of the changes made with the aid of 3-D CT reflected the experience of
      the observers. Overall, there was no improvement in the accuracy of
      interpretations with the addition of 3-D CT.

PMID- 8297078
TI  - Correlation of two-point discrimination and hand function following median nerve
      injury.
AB  - Two-point discrimination (2pd) (moving and static) and object identification were
      assessed in 43 patients after median nerve repair and graft in the middistal
      forearm. The mean age was 37 years (range, 16-78 yr). Twenty-six patients
      underwent primary median nerve repair and 17 had secondary median nerve grafts.
      The minimum follow-up time was 2 years. The values of moving 2pd and static 2pd
      ranged from 2 to > 16 mm. Both moving 2pd and static 2pd had strong correlational
      relationships with hand function as measured by object identification.
      Correlation coefficients for the relationship between 2pd (moving and static) and
      total objects identified ranged from 0.66 to 0.74.

PMID- 8297079
TI  - Effect of skin flap ischemia on plasma endothelin-1 levels.
AB  - A number of studies have been done relating to vasospasm. Vasospasm within the
      microvasculature of a flap can be one of the causes of ischemia and nonviability.
      Endothelin-1 (ET-1), a 21-amino acid polypeptide isolated from vascular
      endothelium culture media, is reported to be one of the most potent
      vasoconstrictors known. This experimental study, using a rabbit epigastric island
      flap, was designed to investigate whether skin flap ischemia influenced plasma ET
      1 levels. After the ischemic insult, blood was drawn from the venous effluent of
      the flaps. Plasma ET-1 levels after 6 hours of ischemia were significantly
      increased compared with nonischemic controls; they were 29 pM, i.e., almost
      enough to induce vasoconstriction of arterioles. These results suggest that ET-1
      is one of the factors responsible for partial necrosis of the skin flap, which
      contributes to the genesis of the no-reflow phenomenon.

PMID- 8297080
TI  - The use of CO2 laser for the treatment of xanthelasma palpebrarum.
AB  - CO2 laser has been used for the treatment of 22 patients with xanthelasma
      palpebrarum. This office procedure done under local anesthesia is fast and easy.
      The lipomatous yellow plaques are accurately photovaporized in a bloodless field,
      layer by layer, until the lesion is totally eradicated. The treated area heals by
      reepithelization, ostensibly with virtually no scar contraction. All our patients
      were satisfied with their results, rating them from good to excellent. In 5
      patients some pigmentation changes were noted. During follow-up periods varying
      from 15 to 54 months, only 2 (9%) patients had recurrences, which were retreated
      successfully. We postulate that treatment of xanthelasma palpebrarum by CO2 laser
      should be seriously considered in most patients.

PMID- 8297082
TI  - Surgical repair of myelomeningocele.
AB  - The birth of an infant with myelomeningocele provides a devastating experience
      for parents, a management dilemma for medical personnel, and an economic
      liability of immense proportions associated with the multiple disciplinary
      management program throughout the patient's life. Although undue delay in the
      onset of therapy is to be avoided, time can be taken for through assessment and
      appropriate discussion with the family without compromising the outcome. Once
      decisions are made to proceed with repair, early cover of the myelomeningocele
      defect is necessary to prevent progressive loss of neural tissue through
      exposure, desiccation, and sepsis. Many techniques of repair have been advocated.
      In principle, the ideal should be applicable to all sizes of defect, should be
      able to be executed in the neonatal age group with minimal morbidity, and should
      provide long-term, stable soft tissue cover without significant secondary
      scarring. A technique adhering to these principles is described and supported by
      results in a personal series of 84 patients during a 12-year period.

PMID- 8297081
TI  - The contralateral breast flap in reconstruction of the breast and chest wall.
AB  - The contralateral breast flap is a useful method of reconstruction of the breast
      and chest wall after the treatment of carcinoma of the breast by surgery and x
      ray therapy. Breast tissue is an excellent donor tissue to solve these difficult
      problems and the only disadvantage is the risk of a second primary breast cancer.
      Young patients with an identifiable high risk of a second primary tumor are not
      suitable for this technique. If, however, we confine the operation to the group
      in whom we are prepared to preserve the breast, with or without a breast
      reduction, then there is no logical reason why the risk should be any greater in
      having the residual breast tissue on two sides rather than one. The operation
      involves the transfer of breast tissue, normally discarded in a breast reduction,
      to the other side in a two-stage procedure; this is a useful method, both for
      reconstruction of the breast and also for repair of the chest wall after
      irradiation damage, particularly in elderly patients. I have found this technique
      to be suitable in approximately 10% of breast reconstructions I have performed;
      there has been no patient with a second primary tumor over a 15-year period in 60
      carefully selected patients.

PMID- 8297083
TI  - Closure of large spina bifida defects: a simple technique based on anatomical
      details.
AB  - Much has been written about closure of large spina bifida defects. There is an
      increased demand to close these defects irrespective of the final outcome of the
      patient. Plastic surgeons may become involved in the closure of large defects.
      Perforator vessels of the back passing through the latissimus fascia can maintain
      viability of triangular island flaps. Therefore, such flaps can be used to close
      the large midline defects of spina bifida. This article reviews the literature
      and presents a simple technique based on anatomical properties of the region
      surrounding the defect.

PMID- 8297084
TI  - Nail plasty in the treatment of duplicated thumb.
AB  - We present refinements in the treatment of duplicated thumb. When applying the
      modified Bilhauts procedure including the nail, this design based on a lunula is
      useful to construct a natural looking nail in Wassel types 2 to 4. No bone
      fixation of each segment is also effective to produce an even transverse
      curvature of the reconstructed nail.

PMID- 8297085
TI  - Vascularized bone flaps for thoracolumbar spinal fusion.
AB  - Vascularized bone flaps for thoracolumbar and lumbosacral spine fusion were
      developed in dissections on 52 cadavers, using iliac wing bone based on (1) the
      quadratus lumborum muscle and (2) the deep circumflex iliac artery. Fifteen
      clinical fusions were performed using these procedures. It was demonstrated
      roentgenologically that these vascularized bone flaps do not undergo resorption
      but maintain bone density 1.5 to 2 times that of nonvascularized bone. Bone flaps
      with a dual blood supply demonstrated increased strength of bony fusion.

PMID- 8297086
TI  - Experimental and clinical use of pH monitoring of free tissue transfers.
AB  - No current method of flap monitoring is ideal for use in all types of free tissue
      transfers. No method provides objective, easily communicated data that is
      identical in all types of transfers. In particular, reliable monitoring of buried
      transfers has proved difficult with available methods. The rat anterior thigh
      flap based on the external iliac vascular pedicle was introduced by us as a model
      of deep free tissue transfer. Four sets of 10 flaps were raised in the following
      groups: Group A (control), Group B (arterial occlusion), Group C (venous
      occlusion), and Group D (arterial and venous occlusion). Postoperative muscle
      flap pH was measured with a micro-pH electrode (1.2 mm) and correlated with
      arterial blood gas. Results showed excellent correlation of flap and serum pH
      over time (mean flap pH, 7.28; mean serum pH, 7.30). Arterial occlusion produced
      a rapid drop in flap pH of 0.66 pH units at 1 hour. Venous occlusion pH drop was
      0.27 pH units at 1 hour, 0.53 pH units at 3 hours. Arterial and venous occlusion
      produced a pH drop of 0.55 pH units at 1 hour. The most rapid rate of pH drop
      occurred immediately after vessel occlusion. We have used continuous pH
      monitoring in 21 free tissue transfers for up to 84 hours after surgery. PH
      values remained constant in each transfer (range, 7.20-7.50; grand mean, 7.35).
      There was one flap failure among the monitored group of flaps, which was
      predicted by pH drop before loss of Doppler pulse.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8297087
TI  - Free transfer of the greater omentum.
AB  - Thirty-seven patients with various coverage problems and with lower extremity
      occlusive disease underwent free transfer of the greater omentum into the defect
      with a favorable clinical success rate. There are a number of advantages of this
      technique for such reconstructive problems.

PMID- 8297088
TI  - Elongation by weight of a bipedicle hair-bearing neck flap.
AB  - We report a patient in whom weight was applied to a tube flap that was raised as
      part of an upper lip reconstruction procedure. Because the flap was found too
      short for transfer, weight was applied and flap elongation was achieved within a
      few days.

PMID- 8297089
TI  - Combined tissue expansion and free tissue transfer for reconstruction of the hand
      in epidermolysis bullosa-associated malignancy.
AB  - The recessive form of dystrophic epidermolysis bullosa (RDEB) is associated with
      severe hand deformities characterized by cocooning pseudopolysyndactyly,
      recurrent ulceration, fibrosis, and adduction contracture of the thumb. In
      addition, RDEB is associated with an aggressive form of squamous carcinoma,
      notable for rapid metastases, appearance at an early age, and a relative
      resistance to radiation or chemotherapy. To date, reported reconstructive
      treatment has been limited to excision with skin grafting or amputation. We
      report the successful combined use of tissue expansion and microsurgical free
      tissue transplantation to reconstruct a patient with RDEB found to have
      malignancy of the hand. Donor skin was found to expand without blistering, and
      use of the expander allowed primary donor site closure after microsurgical
      transplantation of a scapular flap. We recommend wide tumor resection and the
      aggressive use of contemporary reconstructive methods to maintain hand function
      and associated quality of life in patients with RDEB who develop malignancy.

PMID- 8297090
TI  - The use of omental transposition in the treatment of recurrent sarcoma of the
      back.
AB  - We report 2 patients with paraspinous sarcoma treated with omental transposition
      tunneled through a defect in the lumbar fascia that resurfaced in the soft
      tissues of the lower back. Traditional reconstruction with skin flaps was
      unsatisfactory because of prior irradiation to the area. In 1 patient the omentum
      obliterated a cavity connecting the dura to the skin to prevent cerebrospinal
      fluid leak. In the other patient a large soft tissue defect overlying the lower
      back and dura was covered with omentum and skin grafted. Although both patients
      lived < 2 years, the durable wound coverage remained intact over the surgical
      site.

PMID- 8297091
TI  - Volar dislocation of the metacarpophalangeal joint of the thumb.
AB  - A rare case of volar dislocation of the metacarpophalangeal joint of the thumb is
      reported. Open reduction was necessary to correct the deformity.

PMID- 8297092
TI  - Entropion secondary to epiblepharon.

PMID- 8297093
TI  - A method for detection of a punctured saline tissue expander.
AB  - Inadvertent puncture of a tissue expander from a needle can occur both
      intraoperatively and postoperatively. With a small puncture hole and a partially
      filled expander, detection of the hole can be very difficult, especially in the
      postoperative period when removal of the entire device may become necessary for
      adequate examination. A simple method is described to detect the presence of such
      a leak with the use of fluorescein dye.

PMID- 8297094
TI  - The Italian contribution to plastic surgery.
AB  - The birth of what we now call plastic surgery dates to the fifteenth century,
      when the diffusion of nose amputation as a punishment was paralleled by the
      blossoming of surgical procedures for nose reconstruction. The relationship
      between the Eastern and the Western world fostered the spreading of the so-called
      Indian method, based on the use of a forehead flap. This technique was first
      introduced in Italy by the Branca family from Catania, Sicily. Eventually, a
      member of this family switched to a different approach to nose reconstruction
      using a cutaneous arm flap. This "Italian" method was followed and theorized by
      Tagliacozzi in Bologna. From the nineteenth century, distinguished surgeons like
      Sabattini, Tansini, Sterzi, Pieri, and more recently, Sanvenero Rosselli, with
      their pioneering work, substantially improved and helped develop plastic surgery
      in Italy as we know it today.

PMID- 8297095
TI  - A surprise in our stocking.

PMID- 8297096
TI  - Environmental tobacco smoke: the risks of passive smoking in facial surgery.

PMID- 8297097
TI  - Re: Color flow ultrasound for delineating microsurgical vessels: a clinical and
      experimental study.

PMID- 8297098
TI  - Efficacy of pyridoxal treatment in controlling the growth of melanomas in cell
      culture and an animal pilot study.
AB  - We have demonstrated, using confocal laser scanning microscopy, that pyridoxal
      treatment of B16C3 murine melanoma cells inhibits triamcinolone acetonide induced
      translocation of the glucocorticoid receptor to the nucleus of intact cells. In
      addition to inhibiting glucocorticoid receptor nuclear translocation, pyridoxal
      kills B16C3 murine melanoma cells and WM983A human melanoma cells in culture.
      Cortexolone, a glucocorticoid antagonist, also kills cells in culture. This
      mechanism, however, appears to initiate in the glucocorticoid receptor signal
      transducing cascade at a point prior to the impact of pyridoxal treatment alone.
      The glucocorticoid antagonist RU486 has no detrimental effect on melanoma cell
      viability, however, in combination with pyridoxal, RU486 extends cell viability.
      Since pyridoxal kills melanoma cells in culture, a pilot study was carried out
      examining the efficacy of topical application of a pyridoxal cream to inhibit the
      growth and/or cause regression of (B16C3) xenograft melanoma tumors in an
      immunocompetent (Hairless Rhino-J3) and an immunocompromised (Crl: nu/nu (CD1)BR)
      murine animal model. The results of the study with immunocompetent animals are
      encouraging. While tumors are brought under control by pyridoxal treatment,
      further work is needed to determine the most efficacious treatment regimen and to
      establish formal concentrations for pyridoxal in topical ointments. Trials using
      immunocompromised animals indicated that although some qualitative differences
      may be detected between the control and experimental animals, tumor growth in
      these animals is so aggressive that multiple applications or higher
      concentrations of pyridoxal may be needed to obtain useful data.

PMID- 8297099
TI  - Effect of albumin on antitumor activity of diarylsulfonylureas.
AB  - Several diarylsulfonylureas (DSU), including Sulofenur (LY186641) and LY181984,
      have been described that exhibit wide spectrum and high therapeutic activity
      against murine solid tumors and human tumor xenografts. The mechanism for
      antitumor activity is poorly understood. Moreover, in vitro cytotoxic activity in
      serum-containing medium is not predictive of in vivo antitumor activity for DSU.
      Since DSU are extensively bound to serum albumin (> 99%), we sought to determine
      the effect of albumin on tumor cytotoxicity. We adapted human CCRF-CEM leukemia
      and GC3 colon carcinoma cells for growth in UltraCHO serum- and albumin-free
      medium. In comparisons between normal growth medium (RPMI-1640 with 10% fetal
      bovine serum) and UltraCHO medium, the unbound fraction of drug correlated better
      with cytotoxic activity than did the total drug. Tumor cytotoxicity by DSU
      required > 24 h and was markedly enhanced in UltraCHO medium. For example,
      LY181984 and Sulofenur had IC50 values of 7.4 and 12.1 micrograms/ml against CCRF
      CEM in normal growth medium and 0.6 and 0.2 microgram/ml in UltraCHO. Moreover,
      DSU with the lowest IC-50s in albumin-free medium displayed the most potent in
      vivo antitumor activity in the 6C3HED lymphosarcoma. A Sulofenur-resistant CCRF
      CEM cell line was developed by culturing the cells for > 20 passages in UltraCHO
      medium containing LY186641 at 2 micrograms/ml (10X IC-50). This line showed
      approximately 18-fold resistance to LY186641, but did not show cross-resistance
      to vinblastine, actinomycin D, or doxorubicin. The albumin-free conditions may be
      useful for further mechanistic studies on the antitumor action by DSU. Further
      studies are underway to determine whether DSU structural requirements for
      cytotoxicity an albumin binding are intrinsically linked.

PMID- 8297100
TI  - Concentrations of doxorubicin and its metabolites in human autopsy heart and
      other tissues.
AB  - PURPOSE: Since doxorubicin causes cardiotoxicity, we wished to assess relative
      concentrations of doxorubicin and its metabolites in cardiac tissues of patients
      who had been treated antemortem. We also wished to determine factors that
      correlate with human cardiac doxorubicin and doxorubicinol concentrations.
      PATIENTS AND METHODS: Autopsy tissues were collected from 35 patients who had
      received doxorubicin at any time antemortem, and were assayed by high pressure
      liquid chromatography. RESULTS: The major species found in human autopsy cardiac
      tissues were doxorubicinol (median concentration 92 ng/g, range 0 to 484 ng/g),
      and doxorubicin (median 58 ng/g, range 0-1665 ng/g). Other doxorubicin
      metabolites were detected in cardiac tissues in < half the patients. Of ten
      organs studied, heart ranked fifth with respect to median doxorubicin
      concentration and ranked fourth with respect to median doxorubicinol
      concentration. By multiple stepwise regression analysis, factors most closely
      associated with cardiac doxorubicin concentrations were time from last treatment
      divided by dose intensity, serum total protein, albumin, and hemoglobin (negative
      correlations). Factors most closely associated with cardiac doxorubicinol
      concentrations were cumulative doxorubicin dose, total protein, hemoglobin, and
      uric acid (positive associations), and respiratory rate (negative association).
      The physiologic significance of these associations (if any) is uncertain. By
      paired t-tests, cardiac doxorubicin and doxorubicinol concentrations were
      significantly (p < 0.05) higher than concentrations in skeletal muscle and smooth
      muscle organs. CONCLUSIONS: Overall, the results suggest that the much greater
      tendency to develop doxorubicin toxicity in heart than in other types of muscle
      may be due to a propensity of cardiac muscle to accumulate doxorubicin. The
      results also suggest that doxorubicinol may play a role in doxorubicin cardiac
      toxicity, and that doxorubicin may be gradually converted to doxorubicinol in
      human tissues.

PMID- 8297101
TI  - Evaluation of protein kinase inhibitors in an assay system containing multiple
      protein kinase activities.
AB  - Specificities of several known protein kinase inhibitors were evaluated using an
      assay system in which activities of protein kinase A, protein kinase C, protein
      tyrosine kinase and calmodulin-dependent protein kinase III were simultaneously
      detected. Inhibitory spectra of H-89, K252a, H-7, staurosporine, tyrphostin and
      herbimycin A observed in the assay system were similar to those reported in the
      purified protein kinase assay systems. It was also found that KN-62 selectively
      inhibited calmodulin-dependent protein kinase III activity. These data suggest
      that the assay system may be effective and practicable in evaluating
      specificities and screening of new protein kinase inhibitors.

PMID- 8297102
TI  - Effect of S-adenosyl-L-methionine on the development of preneoplastic foci and
      the activity of some carbohydrate metabolizing enzymes in the liver, during
      experimental hepatocarcinogenesis.
AB  - gamma-Glutamyltranspeptidase (GGT)-positive foci and glutathione-S-transferase,
      placental (GST-P)-positive lesions occupied 36% and 54% of liver parenchyma,
      respectively, in Wistar rats 8 weeks after initiation with diethylnitrosamine,
      followed by selection. The administration of S-adenosyl-L-methionine (SAM, 384
      mumol/kg/day) caused 77% and 42% falls in the percentage of GGT-positive and GST
      P-positive lesions, respectively. There also occurred a 46% decrease in labeling
      index of GGT-positive foci, in SAM-treated rats. These changes were associated
      with decrease in liver pyruvate kinase (PK), lactate dehydrogenase and glycerol-3
      phosphate dehydrogenase. SAM did not affect these enzymatic activities in normal
      and uninitiated controls, but it caused a consistent increase in initiated rats.
      Enolase, fructose-biphosphatase and malic enzyme (ME) activities increased in the
      liver of initiated rats. SAM did not modify significantly these enzymatic
      activities, either in control or in initiated rats. Glucose-6-phosphate
      dehydrogenase (G6PDH) was 113% higher in the liver of initiated rats than in
      uninitiated controls. SAM treatment did not significantly affect this enzymatic
      activity in uninitiated rats, but caused a great decrease in initiated ones. As
      expected, there occurred a marked rise in GGT activity in the liver of initiated
      rats, with respect to controls. SAM caused an increase in GGT activity in normal
      and uninitiated controls, but it caused a 77% fall in GGT activity in initiated
      rats, coupled with a 380% rise in remodeling of GGT-positive lesions.
      Histochemical determination of G6PDH and ME activities showed that in the absence
      of SAM many preneoplastic lesions expressed higher G6PDH and ME activities than
      surrounding liver. SAM did not affect ME-positive lesions, while it caused a
      decrease in the number of G6PDH-positive lesions. Immunohistochemical
      determination of PK activity, isoenzyme L, showed a decrease in GST-P-positive
      lesions. Many of these lesions were no longer recognizable as lesions expressing
      a low PK activity, in SAM-treated rats. However, a relatively small number of GST
      P-positive lesions expressing a low PK activity were still present in these rats.
      These data suggest that glucose channelled into triacylglycerol and pyruvate
      synthesis decreases in rat liver, during the development of preneoplastic foci,
      while the production of reducing equivalents and pentose phosphates increases,
      thus favoring DNA synthesis and detoxification reactions. Decrease in DNA
      synthesis, in SAM-treated rats, is paralleled by a partial reversion of
      carbohydrate metabolic features to those present in normal liver.

PMID- 8297103
TI  - In vitro proton NMR spectroscopy of extracts from human breast tumours and non
      involved breast tissue.
AB  - Proton (1H) nuclear magnetic resonance (NMR) spectra were obtained from
      perchloric acid (PCA) extracts of 11 breast tumours and non-involved breast
      tissue from 7 of the same patients. The spectra were correlated with
      histopathologic diagnosis. The tumour group consisted of 8 ductal carcinomas, 1
      ductal carcinoma with an extensive intraductal component, 1 intraductal carcinoma
      and 1 fibroadenoma. Higher content of lactate, succinate and phosphocholine and
      low levels of glucose and inositol were characteristic findings in the tumour
      group as compared to non-involved breast tissue. 1H NMR spectra of PCA extracted
      breast specimens provide a comprehensive window into the metabolic activities of
      the tissue.

PMID- 8297104
TI  - Suramin inhibits the phosphorylation and catalytic activity of DNA topoisomerase
      II in human lung cancer cells.
AB  - Suramin is a prototype of a new class of anticancer drugs. We investigated the
      action of suramin on the signal transduction pathways to DNA topoisomerase II
      (Topo II). Suramin showed a growth-inhibitory effect on a human lung cancer cell
      line (PC-9) with an IC50 of about 160 micrograms/ml. Suramin inhibited the
      catalytic activity of Topo II with an IC50 of about 100 micrograms/ml without
      stabilization of the cleavable complex of DNA and Topo II. Suramin decreased the
      phosphorylation of Topo II with an IC50 of 175 micrograms/ml, but did not change
      the degree of Topo II expression. These IC50 values for inhibition of catalytic
      activity and phosphorylation of Topo II were equivalent to the growth-inhibitory
      dose determined by tetrazolium dye assay. Phosphorylation of the tyrosine
      residues of Topo II was not changed by suramin. In the presence of okadaic acid,
      a potent inhibitor of serine/threonine protein phosphatase, suramin also
      decreased the phosphorylation of Topo II, suggesting that the drug did not act on
      the serine/threonine protein phosphatases inhibited by okadaic acid. Suramin also
      inhibited the protein kinase C (PKC) activity of PC-9 cells. These results
      suggest that suramin decreases the phosphorylation of Topo II mediated by PKC.
      This effect of suramin might cause the inhibition of Topo II activity resulting
      in the growth inhibition of tumor cells.

PMID- 8297105
TI  - Hyperthermic enhancement of cis-diamminedichloroplatinum (II)-induced DNA damage
      in human esophageal cancer transplantable to nude mice.
AB  - The effects of a combination of cis-diamminedichloroplatinum (II) (CDDP) and
      hyperthermia on tumor growth were examined using nude mice bearing a
      transplantable human esophageal cancer (ESO-2). A combination of 4 mg/kg CDDP and
      43 degrees C hyperthermia for 30 min effectively inhibited tumor growth in
      comparison with either treatment alone. Whereas the S-phase fraction was
      decreased for only 3 days with hyperthermia alone, it was decreased for at least
      7 days with the combination of CDDP and hyperthermia. Though the intratumoral
      concentration of CDDP in the heated tumor was 1.4 times higher than that in the
      unheated tumor, the amount of DNA-bound CDDP in the heated tumor was 2.2 times
      higher. The repair efficiencies of CDDP-induced DNA damage showed no significant
      difference between the heated tumor and the unheated tumor. Therefore, it is
      suggested that the enhancement of the antitumor effects of CDDP by hyperthermia
      is dependent on the increase in the initial amount of CDDP-induced DNA damage.

PMID- 8297106
TI  - Metastatic human pleural ovarian cancer model constructed by orthotopic
      implantation of fresh histologically-intact patient carcinoma in nude mice.
AB  - Pleural cancer is a frequently-occurring tumor that is generally refractory to
      therapy. Clinically-relevant animal models of human pleural cancer are greatly
      needed for testing experimental and standard treatments, as well as for
      understanding the clinical features of this disease. We report the first
      orthotopic transplant model for human patient pleural cancer. Fresh
      histologically-intact patient specimens of human pleural ovarian adenocarcinoma
      were implanted onto the visceral and parietal pleura of nude mouse. The human
      tumors grew locally and regionally mimicking the usual human clinical features of
      this disease. Moreover, only visceral pleural implantation subsequently involved
      mediastinal lymph nodes corroborating clinical observations suggesting that
      visceral pleural involvement in pleural cancer represents an advanced-stage
      disease. This model should facilitate basic research of pleural malignancies, and
      stimulate studies of pleural-tumor response to cytotoxic treatment, biologic
      modifiers, and other modalities of therapy.

PMID- 8297107
TI  - The interactions of protein inhibitors with tumour proteases studied in solution
      and immobilised on cell surfaces in frozen sections.
AB  - The cell surface protease guanidinobenzoatase (GB) has been purified from human
      colonic and lung carcinoma tissue by an affinity step involving the binding of
      the enzyme either onto fibrin fibrils or onto agmatine-sepharose. The inhibitor
      protein (I) was extracted from the cytoplasm of tumour cells and isolated by an
      affinity step involving the binding of I to GB on the surface of cultured
      carcinoma cells. The interaction of GB and I in solution was followed by kinetic
      studies employing the release of the fluorescent 4-methylumbelliferone (MU) from
      the synthetic substrate 4-methylumbelliferyl-p-guanidinobenzoate (MUGB). The
      interaction of soluble I with membrane bound GB was followed by using the yellow
      fluorescent probe 9-aminoacridine (9AA) which binds to active GB but not to GB-I.
      The results of these studies demonstrated the presence of isoenzymic froms of GB
      which were recognized specifically by their appropriate isoinhibitor, isolated
      from the appropriate cell type. This high degree of selectivity suggests a cell
      specific regulatory role for the inhibitors and the possibility that they might
      be used for the delivery of cytotoxic molecules to the surface of specific types
      of tumour cells.

PMID- 8297108
TI  - Antitumor activity of low molecular weight fucans extracted from brown seaweed
      Ascophyllum nodosum.
AB  - The effect of low molecular weight fucans (LMW fucans) has been examined on the
      proliferation of tumour cells. These LMW fucans are not active on all tumour cell
      lines. They are not cytotoxic and inhibit CCL39 fibroblast cells and human colon
      adenocarcinoma Colo320DM proliferation (85% and 50% of inhibition respectively).
      The active concentration of sulphated polysaccharide is about 10 micrograms/mL
      for CCL39 cells and 100 micrograms/mL for COLO 320 DM. This inhibitory effect is
      fetal calf serum concentration and cell density dependent. Furthermore, fucans
      are internalized into CCL39 cells within the first hours of incubation. They are
      distributed into the cytoplasmic compartment but not in the nucleus, and are not
      excreted after one week of contact. In the case of COLO 320 DM cells, the same
      fluorescent fucan is not internalized after one week of contact, but remains
      strongly fixed on the cytoplasmic membrane. This inhibitory effect is not
      accompanied by any modifications of the cell distribution in the various phases
      of the cell cycle. There are no significant differences in the antitumor effect
      either between the various LMW fucan or with the crude extract.

PMID- 8297109
TI  - Correlation between successful heterotransplantation of lung tumors in nude mice,
      poor prognosis of patients and expression of Fos, Jun, ErbB1, and Ras.
AB  - In order to examine whether the expression of the oncoproteins might be important
      for the malignancy of tumors, the relationship between the take rate of 88 human
      squamous cell lung carcinomas in nude mice and the expression of protooncogene
      products was analyzed. The expression of c-fos, c-jun, c-ras, c-erbB1, c-neu and
      c-myc at the protein level was investigated by immunohistochemistry. Tumor take
      was assumed if within three months growing nodules were detected and confirmed
      histologically. The take rate of squamous cell lung carcinomas in nude mice was
      49%. Sixty-eight percent of the tumors were positive for Fos, 40% for Jun, 67%
      for Ras, 77% for ErbB1, 35% for Neu and 39% for Myc. Tumors with an
      (over)expression of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1
      and c-ras had a significantly higher take rate in nude mice than tumors without
      an (over)expression of the oncogene products. In contrast, the expression of the
      c-neu and the c-myc genes at the protein level had no influence on the take rate
      of the tumors in nude mice. Interestingly, only patients with tumors with an
      (over)expression of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1
      and c-ras had significantly shorter survival times than patients whose tumors did
      not show an (over) expression of the oncogene products. These results demonstrate
      that the aggressiveness of the tumors visible in the higher take rate of the
      tumors in nude mice and in the shorter survival times of patients can be detected
      by measurement of the expression of c-fos, c-jun, c-erbB1 and c-ras at the
      protein level.

PMID- 8297110
TI  - Adenocarcinoma production in rats administered 1,2-dimethylhydrazine and fed iron
      salt and guar gum diets.
AB  - Iron salts supplemented in a basal ratio, were fed to young Sprague-Dawley male
      rats for prolonged periods and the frequency of colonic adenocarcinomas induced
      by repeated s.c. injection of 1,2-dimethylhydrazine (DMH) at unit base doses of
      9.0 mg/kg, ascertained and compared with the respective controls. In a series
      employing ferric ammonium citrate (0.46% Fe), in addition to ferrous sulfate
      (0.11% Fe) and ferric ammonium sulfate (0.12% Fe), DMH injection was started on
      day 15 and the animals necropsied 22 weeks after the last of 23 doses. The
      general condition was more involved with the 0.46% Fe diet and the total colonic
      lesion numbers were in the control range. However, the ferric ammonium sulfate
      fed group showed a significant increase in tumors in the distal colon portion. In
      the second experiment, 15% guar gum as such and in admixture with ferric ammonium
      sulfate (0.12%) were compared with the respective controls, the first of 20
      weekly dosages of DMH being administered on day 28 of the feeding. At 32 weeks
      following injection 1, the overall lesion differences were not remarkable, but
      the guar gum ratios engendered decreases in the distal colon tumor frequencies.
      In general, lesion incidence was extensive, involving 80-100% of the animals per
      group of the 2 series. Adenocarcinomas occurred in the small intestine and were
      more prominent in the control and 15% guar gum dietary groups but fewer with the
      ferric ammonium sulfate supplement.

PMID- 8297111
TI  - S-cells from a highly N-myc-amplified neuroblastoma are tumorigenic in nude mice.
AB  - Some neuroblastoma tumors when cultured in vitro give rise to N (neuronal) and S
      (non-neuronal) cells, which differ in morphology, state of differentiation, and
      tumorigenicity. Previously, tumor-forming potential was shown to be
      characteristic of N cells but not S cells. We examined cultures of N and S cells
      derived from a well-characterized, N-myc-amplified human neuroblastoma cell line,
      NBL-W, to determine whether these N and S cells also show differential
      tumorigenicity in nude mice. N cells formed tumors in 94% of trials and S cells
      formed tumors in 56% of trials. Although S cell tumors had a longer lag phase
      prior to tumor development, when tumors developed, both N and S cell-derived
      tumors grew rapidly. These results suggest that S cells do not always represent a
      benign component of neuroblastomas.

PMID- 8297112
TI  - The genotoxicity of unsubstituted and nitrated polycyclic aromatic hydrocarbons.
AB  - To determine the DNA damaging properties of unsubstituted and substituted
      polycyclic hydrocarbons, 61 aromatic and heterocyclic compounds were examined for
      the induction of the SOS system in E. coli PQ37. PAH such as
      benzo[ghi]fluoranthene, benzo[j]fluoranthene, benzo[c]phenanthrene,
      benzo[a]pyrene, chrysene, dibenzo[a,1]pyrene, fluoranthene and triphenylene
      showed relatively high genotoxicity. With respect to the nitroarenes, the highest
      genotoxic potencies were exhibited by the dinitropyrenes. The SOS-inducing
      potency of nitroarenes increased from the bicyclic to the tetracyclic ring
      system. Additionally, it was seen that any increase in the extent of nitration is
      paralleled by an increase of genotoxicity. Whereas PAH required metabolic
      activation by hepatic cytochrome P-450 enzymes, nPAH were direct-acting
      genotoxicants.

PMID- 8297113
TI  - Antitumor activity and immunological properties of marine algal polysaccharides,
      especially fucoidan, prepared from Sargassum thunbergii of Phaeophyceae.
AB  - Marine algal polysaccharide, GIV-A from Sargassum thunbergii markedly inhibited
      the growth of Ehrlich ascites carcinoma at the dose of 20 mg/kg per day X10 with
      no sign of toxicity in mice. GIV-A is suggested to be a hexouronic acid
      containing L-fucan sulfate, fucoidan by the analyses of physicochemical
      properties and IR- and NMR-spectra. The results of carbon clearance activity with
      fucoidan demonstrated that it is acting as a so-called activator of the
      reticuloendothelial system. Fucoidan enhanced the phagocytosis and
      chemiluminescence of macrophages. By the immunofluorescent method, binding of the
      third component of complement (C3) cleavage product to macrophages and the
      proportion of C3 positive cells were increased. In crossed immunoelectrophoresis,
      human serum C3 was converted by fucoidan and appeared as the 3rd peak (converted
      C3). The height of the 3rd peak was directly proportional to the doses of
      fucoidan. The residual CH50 units of human serum decreased dose-dependently.
      These results suggest that the antitumor activity of fucoidan is related to the
      enhancement of immune responses. The present results indicate that fucoidan may
      open new perspectives in cancer chemotherapy.

PMID- 8297114
TI  - Some oral carcinomas from Sri Lankan betel/tobacco chewers overexpress p53
      oncoprotein but lack mutations in exons 5-9.
AB  - We reported a low prevalence (11%) of p53 expression detected by
      immunohistochemistry in oral squamous cell carcinomas associated with
      betel/tobacco chewing Sri Lankans (23). Five neoplasms which over-expressed p53
      protein were used in the present study of mutations. Despite extensive sequence
      analysis no mutations were detected in exons 5 through 9 of the p53 gene in all
      the DNA samples of these neoplasms. Thus, over-expression of p53 is not
      necessarily synonymous with mutations in the exons studied, although mutations of
      this gene have been reported in oral and head and neck cancer from Japan and USA.
      The absence of mutations in betel/tobacco related carcinomas in this population
      may derive from differences in aetiology, carcinogen metabolism and
      susceptibility, DNA repair mechanisms and/or genetic predisposition.

PMID- 8297115
TI  - Effect of tumour growth on the macrophage response to the antitumour agent 5,6
      dimethylxanthenone-4-acetic acid.
AB  - Peritoneal macrophages from C3H/HeN mice bearing subcutaneous M-16/C or Spon-2
      mammary carcinomas had enhanced tumouricidal activity over control macrophages
      from non-tumour bearers in response to 5,6-dimethylxanthenone-4-acetic acid (5,6
      MeXAA), a novel antitumour agent which has been scheduled for clinical
      evaluation. The effect of a palpable M-16/C tumour growing in C3H/HeN mice was
      similar to that of Bacillus Calmette-Guerin (BCG) infection, with macrophages
      being fully activated and tumouricidal without any further stimulus being
      required in culture. Macrophages from Spon-2 tumour bearing mice behaved like
      "primed" thioglycollate-elicited macrophages and produced a tumouricidal response
      to 5,6-MeXXA which was significantly higher than that obtained from resident
      peritoneal macrophages from non-tumour bearing mice. Resident and thioglycollate
      elicited macrophages from C3H/HeJ mice were hyporesponsive not only to
      lipopolysaccharide (LPS), but to 5,6-MeXAA as well. Hyporesponsiveness was
      abrogated by BCG infection or by the presence of the M-16/C tumour, but not by
      the presence of the Spon-2 tumour. In response to LPS at low concentrations, or
      to 5,6-MeXAA at all concentrations, tumouricidal activity from macrophages from
      Spon-2-bearing C3H/HeJ mice was severely depressed compared with activity from
      their C3H/HeN counterparts. However, 5,6-MeXAA induced similar levels of
      haemorrhagic necrosis of tumours implanted in either C3H/HeJ or C3H/HeN hosts.
      LPS-induced haemorrhagic necrosis was significantly lower in C3H/HeJ than in
      C3H/HeN hosts. The results show that the presence of subcutaneous tumours
      modulates the activity of peritoneal macrophages in mice.

PMID- 8297116
TI  - Production of hybrids secreting bispecific antibodies recognising CEA and
      doxorubicin.
AB  - A monoclonal anti-CEA secreting hybridoma (11-285-14) was made hypoxanthine,
      aminopterin and thymidine (HAT) sensitive by back selecting it in increasing
      concentrations of 8-azaguanine. Eight 8-azaguanine resistant fusion partners were
      selected based on growth characteristics and continued anti-CEA production. Since
      doxorubicin (Dox) is a hapten, it was conjugated to the carrier proteins keyhole
      limpet hemocyanin (KLH) or bovine serum albumin (BSA) using 1-ethyl-3- (dimethyl
      aminopropyl) carbodiimide. Dox-KLH and Dox-BSA conjugates were used to immunize
      mice and spleen cells from these mice were used for fusions with the HAT
      sensitive anti-CEA partner using standard hybridoma procedures. Enzyme linked
      immunosorbent assays (ELISAs) were developed to test the hybrids obtained for
      anti-CEA, anti-DOX, anti-BSA and bispecific monoclonal antibody (BsMab) activity.
      Sixteen fusions with spleen cells from DOX-KLH immunized mice yielded 621 hybrids
      of which 47 showed low level BsMab activity by ELISA. Eight fusions with spleen
      cells from DOX-BSA immunized mice yielded 297 hybrids. Fifty of these hybrids
      showing dual reactivity have been cloned and subcloned to yield 7 subclones with
      stable BsMab activity for CEA and doxorubicin.

PMID- 8297117
TI  - Exercise training and tumour metastasis in mice: influence of time of exercise
      onset.
AB  - The present study was designed to investigate the factor of timing of activity
      onset in determining the effects of exercise on experimental metastases. After 9
      weeks of wheel running activity (W) or remaining sedentary (S), male C3H/He mice
      received an i.v. injection of CIRAS 1 tumor cells. Mice were then randomized into
      sedentary and wheel running groups (SS, SW, WS, WW) for a further 3 weeks.
      Although the average number of lung tumours did not differ by activity condition,
      the groups exercised prior to tumour injection had a greater incidence in the
      lowest tertile of tumour distribution relative to sedentary controls (SS = 8/20
      vs. WS = 16/19, p < 0.005; SS vs. WW = 14/18, p < 0.05). In a replication trial,
      a similar outcome was present in the lowest tertile: increased incidence of
      animals exercised prior to injection (SS = 3/9 vs. WW = 7/9: p < 0.05). These
      data suggest that exercise training before, but not after, i.v. exposure to
      tumour reduces the number of lung metastases and that the timing of exercise
      onset influences the extent of experimental metastasis in this model.

PMID- 8297118
TI  - A quantitative study of the interphasic nucleolar organizer regions in two human
      cervical carcinoma cell lines.
AB  - We have studied the relationship between interphase nucleolar organizer regions
      (NORs) distribution and nucleolar size in cancer cells under prolonged culture.
      Six morphometric parameters (NUCLEAR SIZE, NOR NUMB, AREA SUM, MEAN AREA, SIZE
      RATIO and SIZE RATIO MEAN) of AgNORs in cancer cells were analyzed by an image
      analyzing system. The results show that the parameters NORN NUMB, AREA SUM and
      NUCLEAR SIZE demonstrate the most consistent changes in the two cervical
      carcinoma cell lines studied. These three parameters of AgNORs appear to be
      correlated with the degree of "dedifferentiation" that occurred in tumor cells
      under prolonged culture.

PMID- 8297119
TI  - Mechanism of growth inhibition of mammary carcinomas by glucarate and the
      glucarate: retinoid combination.
AB  - In synergistic combination 0.75 mmol/kg diet of N-(4-hydroxyphenyl) retinamide
      and 32 mmol/kg diet of glucarate inhibits the growth of primary rat mammary
      tumors, but are equally effective as single agents at 1.5 and 128 mmol/kg diet,
      respectively. Dose-response studies suggest that like retinoids, glucarate acts
      directly on tumor cells, rather than having an adjuvant effect. Although
      synergism is maintained down to at least 0.38 mmol/kg diet of the retinoid,
      experiments using Vitamin A-deficient diets indicates 128 mmol/kg glucarate acts
      independent of retinoid. Both alone and in combination, glucarate and retinoid
      inhibited the growth of human mammary tumor cells grown in the athymic mouse, the
      growth of rat mammary tumors in germfree rats and the hormone-independent MTW
      9a/R rat mammary tumor. Like retinoids, glucarate suppresses protein kinase C and
      induces transforming growth factor-beta, in the mammary tumor cells.

PMID- 8297120
TI  - L-histidinol increases the vulnerability of cultured human leukemia and lymphoma
      cells to anticancer drugs.
AB  - L-Histidinol, a structural analogue of the essential amino acid L-histidine,
      enhances the toxicity of a variety of anticancer drugs for many tumor cells of
      animal origin. In this study, the effects of L-histidinol on the proliferation
      and anticancer drug susceptibility of two human tumor cell lines of lymphoid
      origin, Daudi and MOLT 4, have been examined. L-Histidinol increased the inherent
      capacity of six different antineoplastic agents to kill these human tumor cells,
      in a dose- and time-dependent manner, in spite of the observation that it slowed
      cell cycle progression in both lines.

PMID- 8297121
TI  - Human papillomavirus type 16 DNA in oesophageal squamous cell carcinoma.
AB  - Recent studies, mainly from high risk areas of oesophageal cancer (OC), have
      suggested a possible role of oesophageal infection with human papillomavirus
      (HPV) in the carcinogenesis of OC. Twenty-two cases of OC (among them 20 cases of
      squamous cell, 1 case of verrucous and 1 case of adenoid cystic carcinoma)
      originating from a middle risk area of OC, were analysed by in situ hybridization
      (ISH) and polymerase chain reaction (PCR) to demonstrate HPV infection. No
      evidence of HPV DNA was found using ISH. By PCR, the presence of HPV DNA was
      detected in 1/3 (33%) of early and 1/17 (5.7%) of advanced squamous cell
      carcinoma cases. After digestion of PCR products using seven restriction
      endonucleases, the restriction enzyme digestion patterns were found to be unique
      for HPV type 16 in both positive cases of OC. All other squamous cell carcinomas,
      the case of verrucous carcinoma and that of adenoid cystic carcinoma were
      successfully amplified only with internal control human beta-globin primers. Our
      results are comparable with those from high risk areas of OC and support the HPV
      may be involved in the carcinogenesis of this malignancy.

PMID- 8297122
TI  - False DNA aneuploidy in canine and human neoplasms.
AB  - In most cases, the appearance of aneuploid peaks in DNA histograms may be an
      artefact of tissue preparation or it may reflect non-stoichiometric dye binding
      of a cellular subpopulation rather than true DNA aneuploidy. This report reviews
      how false DNA aneuploidy can be recognized and eliminated from sample submitted
      for DNA flow cytometric analysis.

PMID- 8297123
TI  - Antiproliferative effect of tyrosine kinase inhibitors in epidermal growth factor
      stimulated growth of human gastric cancer cells.
AB  - AGS human gastric cancer cells were characterized to possess EGF receptors.
      Scatchard analysis revealed a half saturation constant of 0.6 nM and 9000
      receptors per cell. Exogenously added EGF stimulated gastric cancer cell growth
      in a dose-dependent manner with a maximum effect of +38% at 10 nM EGF. Inhibition
      of the EGFR-associated tyrosine kinase by genistein and the tyrphostins RG-13022,
      RG-14620 and RG-50864 resulted in a dose-dependent growth inhibition with half
      maximal inhibition at 10 microM, 7 microM and 23 microM, respectively. EGF
      mediated growth stimulation was dose-dependently reversed by coincubation with
      genistein. At genistein concentrations exceeding 6 microM serum-stimulated growth
      of AGS cancer cells was also inhibited. We conclude that EGF is an important
      growth factor for AGS gastric cancer cells. Inhibition of the EGFR-associated
      tyrosine kinase seems to be an effective antiproliferative principle in EGFR
      positive human gastric cancer cells.

PMID- 8297124
TI  - Release of immunosuppressive factor(s) by MOPC-315 murine plasmacytoma cells: a
      possible mechanism of defence.
AB  - Supernatants were collected from suspensions of MOPC-315 tumor cells harvested
      from ascitic tumors and kept for 24 hours in culture medium and from cultures of
      an MOPC-315 tumor-cell kept for a long period of time in vitro. The MOPC-315
      supernatants were tested for immunosuppression of mitogenic stimulation of BALB/c
      spleen cells by ConA or LPS, of allogeneic response of effector BALB/c spleen
      cells against target C57BL spleen cells, of generation of antibody response
      against SRBC and of induction of LAK activity. The immunosuppression was marked
      in all the test systems, was not related to secretion of either C-type particles
      or of anti-TNP antibodies and was also induced by MOPC-315 tumor cells kept in
      serum-free medium. It is suggested that release of immunosuppressive factor(s) by
      MOPC-315 tumor cells might play a role in the mechanism(s) of defence of the
      tumor against the host.

PMID- 8297125
TI  - Cathepsin-D in human breast cancer: correlation with vascular invasion and other
      clinical and histopathological characteristics.
AB  - The relationship between the Cathepsin-D concentration in breast cancer cytosols
      and clinical and histopathological characteristics of the tumours was
      investigated, including vascular invasion, histological type, histological grade,
      lymph node involvement and tumour size. The median cathepsin-D concentration of a
      series of 738 primary breast carcinomas was used to define "low" and "high"
      cathepsin-D. High cathepsin-D concentration was associated with peritumoral
      vascular invasion, with high grade infiltrating duct carcinomas, with tumours of
      > or = 2 diameter, and with metastases in the axillary lymph nodes. Low cathepsin
      D concentration was associated with in-situ carcinomas.

PMID- 8297126
TI  - Inhibition of potentially lethal damage recovery by cisplatin in a brain tumor
      cell line.
AB  - Radiation resistant tumours such as gliomas show enhanced capacity for
      potentially lethal damage recovery (PLDR), which can be inhibited by cisplatin.
      The 9L rat brain tumour cell line, like human glioma cell lines, shows a large
      capacity for PLDR. Cisplatin administered at 6 micrograms/ml for 1 hour
      immediately following acute irradiation (18 Gy) is shown to cause significant
      inhibition of PLDR, while 3 micrograms/ml causes little inhibition. Cisplatin
      radiation treatment sequence affects PLDR inhibition, with maximum effect seen
      when cisplatin is administered immediately after irradiation, during the period
      of rapid cellular recovery. These data suggest that optimum interaction between
      radiation and cisplatin treatments can be achieved by maximizing intratumoural
      cisplatin levels during the post-irradiation recovery period.

PMID- 8297127
TI  - Genomic PCR-SSCP analysis of the metastasis associated NM23-H1 (NME1) gene: a
      study on colorectal cancer.
AB  - To facilitate further mutational analysis of NM13-H1, a human metastasis
      suppressor gene, we have established its genomic organization. NM23-H1 is
      composed of five exons, spanning a genomic DNA fragment of 10 kb. Using
      oligonucleotide primers flanking each exon, PCR-SSCP analysis was performed on
      genomic DNAs of healthy individuals. A common polymorphism, a C to T transition,
      was detected 30 nucleotides upstream from the 5' splice site flanking exon 1. As
      NM23-H1 allele loss and altered expression have been reported in colorectal
      cancer, genomic DNAs of 20 colorectal tumors were analyzed for the presence of
      gene-specific mutations by PCR-SSCP: no abnormal sequences were detected within
      the coding and splice site regions of the NM23-H1 gene. This finding suggests
      that NM23-H1 mutations are rare events in human colorectal cancer.

PMID- 8297128
TI  - Chemosensitisation of alkylating agents by pentoxifylline, O6-benzylguanine and
      ethacrynic acid in haematological malignancies.
AB  - The effects of resistance modifiers (RM) on the cytotoxicity of mafosfamide
      (MAF), bis-chloroethylnitrosourea (BCNU) and dacarbazine (DTIC) were evaluated by
      the MTT colorimetric assay in isolated lymphocytes and blast cells derived from
      patients with chronic lymphatic leukaemia (CLL; n = 28) and acute myeloid
      leukaemia (AML; n = 30), or from healthy donors (n = 19). Pentoxifylline (PTX)
      has been shown to restore sensitivity to alkylating drugs by interfering with DNA
      repair. PTX (10 microM) significantly sensitised leukaemic blasts to the
      cytotoxic effect of MAF. In 8 out of 30 AML samples, sensitisation ratios (SRs;
      i.e. cytotoxic drug ID50s in the presence or absence of RM) for MAF in the
      presence of PTX were > 2 ranging up to 4.2. Inhibition of the DNA repair protein
      O6-alkylguanine-DNA alkyltransferase (AGT) by O6-benzylguanine (O6-BG; 50 microM)
      enhanced the cytotoxicity of DTIC in CLL lymphocytes. SRs > 2 for DTIC in the
      presence of O6-BG were observed in 7 out of 28 CLL specimens. Sensitisation was
      generally greater in the more chemo-resistant specimens. Ethacrynic acid (EA; 1
      microM), an inhibitor of glutathione-S-transferases (GST), failed to influence
      the cytotoxicity of alkylating agents in any cell type. Also, all examined RMs
      did not sensitive leukaemic cells to the cytotoxic effect of BCNU. The data show
      significant chemosensitisation of leukaemic cells to alkylating agents by PTX and
      O6-BG, indicating a potential clinical use of these substances as RM in patients.

PMID- 8297129
TI  - The effect of different dosages of degradable starch microspheres (Spherex) on
      the distribution of doxorubicin regionally administered to the rat.
AB  - To increase the effectiveness of intra-arterial treatment, embolizing agents are
      used. DSM (Spherex) is a starch microsphere suspension--mean diameter 45 mu-
      which can be used repeatedly to produce a transient vascular occlusion for about
      half an hour. It has been used experimentally and clinically in the treatment of
      liver cancer to increase the efficacy of drugs such as doxorubicin. In the
      present study the effect of DSM on the distribution of 14C-labelled doxorubicin
      was investigated in rats with liver tumours. A previously used pharmacological
      dose of 30 mg/kg DSM was compared to a lower dose of 12.5 mg/kg, especially
      regarding the intrahepatic distribution of co-injected drug at two and twelve
      hours after injection. The lower dose was to found to give a more effective
      tumour targeting as well as less regional toxicity. The results of the present
      study show that in experimental models lower doses of DSM should be beneficial.

PMID- 8297130
TI  - Inhibitory effects of flavonoids on xanthine oxidase.
AB  - The stems of Bougainvillea spectabillis Wild (Nyctaginaceae) have been used in
      folk medicine for hepatis, and spinasterol and quercetin were isolated and
      characterized from the plant leaves in this study. These constituents have not
      been previously isolated from Bougainvillea spectabillis W. Quercetin, the
      flavonoid, was found as active principle because it showed a strong activity on
      xanthine oxidase inhibition (IC50 = 7.23 microM) in this study as well as in the
      literature. Since xanthine oxidase serum levels are increased in hepatitis and
      tumoral brain tissues, quercetin may be used for remission of hepatitis or brain
      tumor. In order to study the structure-activity relationship of the flavonoids as
      regards xanthine oxidase inhibition, nine naturally occurring flavonoids have
      been tested the inhibitory effects on xanthine oxidase, such as baicalein,
      baicalin, capillarisin, d-catechin, d-epicatechin, hesperidin, liquiritin,
      puerarin and wogonin. The results showed that baicalein displayed the strongest
      activity (IC50 = 9.44 microM), followed by wogonin (IC50 = 52.46 microM) and then
      baicalin (IC50 = 71.73 microns). Baicalein induced uncompetitive inhibition of
      the enzyme with respect to xanhtine and the apparent inhibition constant (Ki) was
      2.48 x 10(-6) M.

PMID- 8297131
TI  - Chronology of combined chemotherapy (5FU) and radiotherapy. I. In vitro study.
AB  - Since radiotherapy or chemotherapy alone may be ineffective, they are more and
      more often combined. In this in vitro studies the effects of the chronology of
      the treatments and of the time interval between them are evaluated. In murine
      leukaemia L1210 cells and in murine mammary adenocarcinoma Ca755 cells the
      highest efficacy, i.e. the lowest survival fraction, was observed when
      radiotherapy was administered 6 h before Fluorouracil (FU). To mimic treatment in
      man, a daily combined treatment was also tested. Under these circumstances, the
      chronology of the treatments and the time interval between them had different
      consequences, the highest efficacy being noticed when both treatments were given
      at the same time.

PMID- 8297132
TI  - Chronology of combined chemotherapy (5FU) and radiotherapy. II. In vivo study.
AB  - In a previous study, we reported that repeated combined chemotherapy and
      radiotherapy, and a single combined treatment had different consequences. In this
      study the effect of the chronology of the repeated combined treatments was
      tested, i.e. it was determined whether the treatment is more efficient when the
      first treatment is Fluorouracil or irradiation, or when they are given
      simultaneously. It was first demonstrated that, under our conditions, neither
      radiotherapy nor chemotherapy were chronodependent. The combined treatments were
      more efficient that the single treatment although their chronology had no
      significant consequences. Nevertheless, the simultaneous treatment appeared
      slightly better than the administration of Fluorouracil 6 h before or 6 h after
      irradiation. These results confirm our in vitro experiments.

PMID- 8297133
TI  - Regional intraarterial infusion of methotrexate with leucovorin rescue in a rat
      tumor model.
AB  - Walker 2S6 carcinosarcoma was transplanted in the paw of 52 male Wistar rats. A
      week later, the animals were divided into 6 separate groups and treated in
      different ways, as follows. Group I (control): no treatment. Group II: femoral
      artery ligation (FAL). Group III: ligation-intraarterial chemotherapy (LIC) with
      methotrexate (MTX). Group IV: the same treatment followed by leucovorin rescue
      (LIC+RES). Group V: tourniquet intraarterial chemotherapy and rescue (TIC+RES).
      Group VI: the same treatment applied via the iliac artery (iliac TIC+RES). The
      best results (primary tumor eradication: 8/10 cases, propagation of the tumor to
      the inguinal region: 4/10 cases, necroses of the distal part of the paw: 0/10
      cases, p > 0.05) were observed in group VI, where iliac LIC+RES was performed.
      Analysis of the treatment's mechanism of action revealed that there is an area of
      optimal treatment in the middle of the limb, and two peripheral zones of under
      treatment. At the proximal zone (inguinal region) propagation of the tumor can
      occur, whereas at the distal zone necrosis of the paw can be manifested.

PMID- 8297134
TI  - Increased cytotoxicity of 5'-deoxy-5-fluorouridine by prolonged culture with
      folinic acid.
AB  - We investigated the cytotoxic potentiation by folinic acid (FA) of two
      fluoropyrimidines, 5-fluorouracil (FUra) and 5'-deoxy-5-fluorouracil (5'-dFUrd),
      against two human neoplastic cell lines (HeLa and KSE-2 cells). The
      concentrations of fluoropyrimidine (2-10 microM) and FA (1 microM) in media were
      based on clinically achievable levels, and the duration of culture was relatively
      long (6 days). The cytotoxic activity of fluorouridine and FA was evaluated by
      both clonogenic efficiency and thymidylate synthase (TS) inhibition rate of the
      cells. After combined treatment with 2 microM 5'-dFUrd and 1 microM FA the
      clonogenic efficiencies of the two cell lines were significantly lower than those
      after treatment with 5'-dFUrd alone (p < 0.01). Moreover, the TS inhibition rates
      of these two human cell lines after combined treatment with 10 microM 5'-dFUrd
      and 1 microM FA were significantly higher than those after treatment with 5'
      dFUrd alone (p < 0.01). However, when these two cell lines were exposed to FUra,
      concomitant treatment with FA did not enhance cytotoxicity. These differences in
      the cytotoxic properties of FUra and 5'-dFUrd in response to the addition of FA
      ascribed to the fact that during 2-3 days and 5-6 days after treatment,
      intracellular concentrations of 5'-dFUrd produced by combined treatment with 10
      microM 5'-dFUrd and 1 microM FA were higher than those associated with 10 microM
      5'-dFUrd achieved by combined treatment with 5'-dFUrd and FA was also higher than
      that of FUra during combined treatment with FUra plus FA and that of 5'-dFUrd
      during treatment with 5'-dFUrd alone. There was no statistically significant
      difference in intracellular FUra concentrations between combined treatment with
      FUra plus FA and treatment with FUra alone. Prolonged treatment with 5'-dFUrd and
      FA in clinically feasible concentrations was thus more effective than the
      combination of FUra and FA in two human neoplastic cell lines.

PMID- 8297135
TI  - Immunocytochemical study on internalization of anti-carbohydrate monoclonal
      antibodies.
AB  - The fate of anti-tumor monoclonal antibodies (mAbs) after binding to the cell
      surface is one of the important factors for application of mAbs in therapy. For
      mAbs to remain on the cell surface for a long time is preferable character for
      complement-dependent cytotoxicity (CDC) and antibody-dependent cellular
      cytotoxicity (ADCC). On the other hand, quick internalization of mAbs into
      cytoplasm is advantageous for cytotoxic effects of toxins or cytotoxic drugs
      conjugated with mAbs. In this study we investigated the localization of anti
      carbohydrate mAbs in vitro by immunocytochemical methods at the electron
      microscopic level. Anti-ganglioside GM3 mAb (mouse IgM) was localized both in
      cytoplasmic vesicles and on the cell surface membrane of mouse melanoma cells
      after incubation for 30 min at 37 degrees C. Anti-ganglioside GM2 mAb (mouse
      IgM), anti-ganglioside GD2 mAb (mouse IgG3) anti-ganglioside GD3 mAb (mouse IgG3)
      mainly existed on the cell surface of human small cell lung carcinoma cells,
      human neuroblastoma cells and human melanoma cells, respectively, after
      incubation for 30 min at 37 degrees C. On the other hand, anti-sialyl Lea mAb
      (mouse IgG1) was intensively incorporated into the cytoplasm of human colon tumor
      cells under the same conditions. Anti-ganglioside GD3 mAb and anti-sialyl Lea mAb
      were radiolabelled with 125Iodine and traced in in vitro culture. When the cells
      were incubated in the presence of the 125I-mAb for 90 min on ice, the ratio of
      intracellular counts to surface counts was 8/92 for anti-ganglioside GD3 mAb and
      31/69 for anti-sialyl Lea mAb respectively. After the subsequent incubation for
      60 min at 37 degrees C, the ratio altered to 13/87 for anti-ganglioside GD3 mAb
      and 54/46 for anti-sialyl Lea antigen mAb. This study suggested that
      internalization of anti-carbohydrate mAbs after the binding to the cell surface
      was different among the mAbs depending on the character of antigens. In
      conclusion, anti-ganglioside mAbs have beneficial characters for CDC or ADCC
      while anti-sialyl Lea mAb is suitable for immunoconjugates.

PMID- 8297136
TI  - c-Jun phosphorylation in signal transduction and gene regulation.
AB  - This study analyzed the post-translational regulation of the transcription factor
      AP-1 on the level of c-Jun phosphorylation. For this purpose a new assay system
      employing a histidine-tag method of transient expression and rapid purification
      of recombinant c-Jun, in conjunction with "southwestern" blotting and in situ
      phosphatase treatment, was developed. It is demonstrated that the specific DNA
      binding potential of c-Jun which is dependent on dephosphorylation can be
      modulated both by extracellular and endogenous factors. Exposure of cells to
      phorbol esters as well as artificially increasing the intracellular concentration
      of AP-1 target sites can stimulate the DNA-binding function of c-Jun. These
      results indicate the existence of a novel cellular mechanism that serves to
      dynamically adjust the activity of c-Jun to the number of accessible responsive
      genes.

PMID- 8297137
TI  - In vitro studies on interaction of 4-hydroperoxy-ifosfamide and radiotherapy in
      malignant gliomas.
AB  - Drug-radiation multimodal chemotherapy for malignant brain tumor cells was
      stimulated in vitro by a recently developed computer program, based on evaluation
      of 3D-response surfaces and interaction isoboles. Three malignant glioma tumor
      cell cultures (HTZ17, 146 and 209 B) were sequentially treated in vitro by
      increasing doses of 4-hydroperoxy-ifosfamide, according to in vivo/in vitro
      pharmacokinetic correlation (0.01 to 10 microM), and increasing single doses of
      Gamma-radiation (clinical60Co-radiotherapy unit, 0.26 to 4 Gy or 1 to 3.38 Gy,
      respectively). After approximately five population doubling times with standard
      tissue culture conditions, 3H-Tdr-incorporation was determined by a liquid
      scintillation counting protocol. Data points were evaluated for mono- and
      combined treatment dose-effects. A model-free 3D-response surface was created and
      compared to the theoretical additive response surface. Local additivity was
      analysed for any desired ratio of combined treatment as well as for isoboles. No
      significant sub- or supraadditive effects were observed, indicating additive
      effects in all 3 tumors. No sequence dependence of effects could be demonstrated.
      In case radiotherapy and ifosfamide-chemotherapy are active treatment modalities
      and additive effects are found, we conclude that the combination of ifosfamide
      and radiotherapy might be attractive for the treatment of malignant brain tumors
      and should be further studied.

PMID- 8297138
TI  - Differential expression of extracellular matrix proteins and integrins in
      hepatocellular carcinoma and chronic liver disease.
AB  - Extracellular matrix (ECM) molecules play an important role in the orderly
      development, differentiation and function of tissues. The interaction of ECM with
      heterodimeric transmembrane glycoproteins called integrins is thought to be an
      important factor in cell-cell and cell-substrate adhesions in tumours, tumour
      invasion and metastases. PURPOSE: To investigate ECM and adhesion molecules in
      hepatocellular and breast carcinomas, chronic hepatitis and hepatic cirrhosis.
      MATERIALS AND METHODS: Frozen in liquid nitrogen and also paraffin-embedded
      biopsies from hepatocellular adenomas (3), well-differentiated (53) and poorly
      differentiated (19) hepatocellular carcinomas, lobular (3) and poorly
      differentiated (7) breast carcinomas, chronic hepatitis (10) and hepatic
      cirrhosis (10) were collected and investigated. Immunohistochemical techniques
      were applied for the detection of ECM molecules fibronectin, laminin, tenascin,
      vitronectin and integrins alpha 5 and beta 4. RESULTS: Poorer differentiation of
      the tumours was characterised by up-regulation of fibronectin, tenascin and
      vitronectin and downregulation of laminin and both integrins. These changes were
      observed in the interface between tumour and invaded tissues and within cancerous
      sinusoids. CONCLUSION: Increased expression of some ECM glycoproteins around
      tumour foci suggests a role in stimulating cancer cells or a host defence
      mechanism accompanied by desmoplastic response to them. Downregulation of laminin
      in poorly differentiated tumours identifying loss of basement membrane components
      and parallels quantitative changes in the expression of adhesion molecules in
      both hepatic and breast carcinomas. This may be an important step in enhancing
      local invasiveness of tumour cells, facilitating tumour spreading and biological
      malignancy.

PMID- 8297139
TI  - Interphase cytogenetics and flow cytometry analyses of renal tumours.
AB  - Fluorescent in situ hybridization (FISH) can be used to determine chromosome
      changes in human neoplasia. In our study, we have tested the feasibility of FISH
      to interphase cells of renal carcinoma to evaluate chromosome aneuploidies. We
      carried out in parallel in situ hybridization and flow cytometric studies in
      order to evaluate the possible correlation between numerical chromosome
      abnormalities and ploidies detected by flow cytometry (FCM). The ploidy of
      chromosomes 7, 11, 17 and 18 was investigated in three cases of this tumour
      utilizing specific probes. We found evaluable and comparable results in every
      case of renal carcinoma analyzed for both FISH and DNA FCM analyses and our
      results indicate that fluorescent in situ hybridization with chromosome-specific
      repetitive DNA probes can serve as a cytogenetic tool for the detection of
      numerical specific chromosome abnormalities of interphase nuclei of renal
      carcinoma.

PMID- 8297140
TI  - Monitoring of smokeless tobacco consumers using cytogenetic endpoints.
AB  - Smokeless tobacco consumption is causally associated with oral cavity cancers;
      however, extensive cytogenetic studies have not been done. In the present study,
      individuals consuming dry snuff or tobacco with lime have been studied for
      frequency of micronucleated cells (MNC) in exfoliated buccal mucosa and
      chromosome aberrations (CA) and sister chromatid exchanges (SCE) in lymphocytes.
      The significant elevation in the values of all the three cytogenetic markers
      among tobacco users compared to the controls reveal the extent of genomic damage
      on target and nontarget tissues. The findings emphasize the possible use of
      cytogenetic endpoints for monitoring smokeless tobacco consumers.

PMID- 8297141
TI  - Acute effects of gallium chloride on ventricular function and metabolism of the
      Langendorff perfused rat heart.
AB  - The effects of two concentrations of GaCl3 (1.79 microM and 7.17 microM) were
      studied on isolated perfused paced rat hearts. All hearts were submitted to an
      equilibration period of 20 minutes under normal conditions of oxygenation (95%
      O2, 5% CO2) and with 11 mM glucose in Krebs-Henseleit buffer. At the end of the
      perfusion (80 min) tissue Ga contents were 98.0 +/- 13.8 and 200.2 +/- 28.5 nM/g
      of wet weight for the lower and the higher Ga concentrations respectively. Left
      ventricular developed pressure (LVdp) as well as +LVdp/dt and -LVdp/dt were
      similar in control and Ga-treated groups during the 60 minutes following the
      equilibration period. At the same time mean coronary flow and oxygen consumption
      were lower (p < 0.05) in hearts perfused with 7.17 microM Ga than in the control
      group. Lactate production did not differ in the control and Ga-treated groups.
      Mean creatine kinase release was lower (p < 0.05) in the 7.17 microM Ga-treated
      group than in the 1.79 microM Ga-treated and control groups. Intratissular
      malondialdehyde as well as glycogen and ATP concentrations did not differ in all
      groups at the end of the experiment. Gallium chloride partially prevented the
      unavoidable oedema resulting from using saline Krebs-Henseleit solution. In
      conclusion, acute GaCl3 administration improves the functionality of the
      Langendorff-heart model.

PMID- 8297142
TI  - Puromycin-elicited c-myc mRNA superinduction precedes apoptosis in HL-60
      leukaemic cells.
AB  - The phenomenon of superinduction refers to the process by which high
      concentrations of protein synthesis inhibitors augment and stabilize mRNA
      transcript levels, e.g. 36-180 microM of Puromycin (PM) has been found to elicit
      c-myc mRNA superinduction. The expression of the proto-oncogene c-myc has been
      strongly variously implicated in the regulation of the apoptotic cascade. Since
      we recently found that a low dose of the protein synthesis inhibitor PM activated
      the apoptotic cascade in HL-60 leukaemic cells, the current study was undertaken
      to examine c-myc mRNA transcript levels in such cells, and to assess the
      relationship, if any, between PM-elicited c-myc mRNA superinduction and
      subsequent activation of the apoptotic cascade. PM was employed in vitro at doses
      of 0.9 microM and 2 microM. Dose-dependent c-myc mRNA superinduction was present
      at 1 hour of PM-exposure, and was associated with subsequent activation of the
      apoptotic cascade at 24 hours of exposure. Apoptosis was confirmed
      morphologically as evidenced by chromatin condensation, nuclear fragmentation and
      the formation of apoptotic bodies, and by DNA agarose gel electrophoresis which
      showed the pattern of double-stranded DNA fragments that result from the
      activation of an endogenous endonuclease. [C14]Leucine incorporation studies at 1
      hour demonstrated minimal protein synthesis inhibition at doses used, suggesting
      that c-myc mRNA superinduction in this context may have been the result of
      mechanisms which were independent of the inhibition of synthesis of new proteins,
      such as interruptions in signal transduction.

PMID- 8297143
TI  - In vitro antitumor activity of a new platinum complex, DWA2114R against human
      tumor cell lines.
AB  - The in vitro antitumor activities of a new platinum complex, (-)-(R)-2
      aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate
      (DWA2114R), against various human tumor lines (23 solid tumor lines and 6
      hematopoietic malignant lines) were examined in comparison with those of cis
      diammine (1,1-cyclobutanedicarboxylato) platinum(II) (CBDCA) and cis
      diamminedichloroplatinum(II) (CDDP). The growth inhibitory activities of the
      compounds were estimated by MTT assay after the incubation of cells under
      continuous exposure to the drug. The mean concentrations (microM) of DWA2114R,
      CBDCA and CDDP needed to inhibit the proliferation of cells by 50% (IC50) were
      64.0, 55.1 and 6.8 against solid tumor lines and 8.5, 7.4 and 1.7 against
      hematopoietic malignant lines, respectively. Comparing the drug sensitivity of
      the solid tumor lines by type, ovarian cancer was found to be the most
      susceptible to all three compounds. The susceptibilities of other tumors were in
      the order prostate, breast and colon cancers for DWA2114R and CBDCA but colon,
      prostate and breast cancers for CDDP. The correlations of the mean IC50 values
      for all three combinations of the two compounds were statistically evaluated. A
      significant correlation was shown between DWA2114R and CBDCA, or CBDCA and CDDP,
      but not between DWA2114R and CDDP. These results suggest that DWA2114R is almost
      equivalent in effect to CBDCA which is several times less potent than CDDP, but
      also that the in vitro cell line subpanel specificity of DWA2114R is in certain
      respects different from CDDP, in contrast with CBDCA.

PMID- 8297144
TI  - Dehydroepiandrosterone antiestrogenic action through androgen receptor in MCF-7
      human breast cancer cell line.
AB  - The possible mechanisms of the inhibitory effect of Dehydroepiandrosterone (DHEA)
      on the estrogen-induced growth of MCF-7 human breast cancer cells were explored.
      The impairment of metabolic pathways, via the inhibition of glucose-6-phosphate
      dehydrogenase (G6PD) activity, was excluded: G6PD activity in MCF-7 homogenate
      was reduced by DHEA only at a very high concentration (50 microM), while no
      inhibitory action on the enzyme activity was detected when DHEA was added at the
      antimitotic concentrations (0.02-0.5 microM). A steroid receptor mediated effect
      was explored: DHEA might either activate androgen receptors (AR) or partially
      displace E2 from estrogen receptor (ER). The pure antiandrogens Flutamide and
      Hydroxyflutamide reversed the inhibitory effect of DHEA on MCF-7 cell growth,
      whereas both the nonsteroidal estrogen Diethylstilbestrol and the antiestrogen
      Tamoxifen were ineffective. Results demonstrate that the AR activation plays a
      pivotal role in the inhibitory action of DHEA on the E2-induced MCF-7 growth.

PMID- 8297145
TI  - Effect of benzo[a]phenothiazines on natural killer cell activity of human
      peripheral blood mononuclear cells.
AB  - Four benzo[a]phenothiazines were investigated for their effects on antibody
      dependent cellular cytotoxicity (ADCC) and natural killer (NK) cell and blast
      transformation of human peripheral blood mononuclear cells (PBM).
      Benzo[a]phenothiazines dose-dependently suppressed the nitrogen-stimulated T cell
      proliferation. The suppressive effect of non differentiation-inducing
      benzo[a]phenothiazines was higher than that of differentiation-inducing
      benzo[a]phenothiazines. The stimulation effect of differentiation-inducing
      compounds on the NK activity was reduced by removal of monocytes from the PBM.
      The results suggest the direct activation of monocytes (Mo) by differentiation
      inducing benzo[a]phenothiazines.

PMID- 8297146
TI  - Microwave fixation of nuclear matrix in tumor cells.
AB  - Microwave irradiation provides good fixation of human and animal tissues for
      light and electron microscopy. In this study, microwave irradiation was used for
      the fixation of cytoplasmic and nuclear matrix in tumor cells. The nuclear matrix
      appears well preserved and exhibits a network formed by thick and thin filaments.
      Hence microwave fixation can be used as a quick and effective method for the
      study of the morphology of nuclear matrix.

PMID- 8297147
TI  - Elimination of malignant tumor cells from human bone marrow using monoclonal
      antibodies and immunomagnetic beads.
AB  - Conditions for depletion of malignant tumor cells from human bone marrow using
      monoclonal antibodies and immunomagnetic beads were studied. Human hepatoma
      HA22T/VGH cells labeled with the supravital DNA binding dye Hoechst 33342 were
      seeded into normal human bone marrow at a ratio of tumor cells to marrow cells of
      1:9. The immunobeads used were M-450 magnetic microspheres coated with sheep anti
      mouse immunoglobulin. The marrow-tumor cell mixtures were incubated with a panel
      of antihuman hepatoma cell monoclonal antibodies (9B2, E10A1, and C2E6) at 4
      degrees C for 40 min, and then reacted with immunomagnetic beads for 60 min
      longer. After incubation, the bead-coated tumor cells were removed from the
      marrow with a magnetic particle concentrator. Tumor residual was measured in a
      limiting dilution test, and the recovery of marrow progenitor cells was assessed
      by CFU-GM assay. The efficiency of tumor depletion was closely related to the
      amount of monoclonal antibody bound to tumor cells and the immunobead/tumor cell
      ratio. Monoclonal antibodies used in combination were more effective than their
      individual use alone. Two cycles of purging with both monoclonal antibodies and
      immunomagnetic beads resulted in an apparent improvement in tumor depletion as
      compared with one cycle. Using a cocktail of three monoclonal antibodies and
      purging the marrow for two cycles, 4 to 5 logs of tumor cells could be removed
      with a sufficient recovery (70%) of CFU-GM. However, multiple purging treatments
      (> or = 3 cycles) would be apparently damaging to hematopoietic progenitor cells.

PMID- 8297148
TI  - The efficacy of phloridzin and phloretin on tumor cell growth.
AB  - This study utilized phloridzin (P1) and its aglucone phloretin (P2), two known
      inhibitors of glucose transmembrane transport, to inhibit tumor cell growth in
      vivo. The efficacy of hydrazine sulfate as an anticachexic agent was also
      evaluated. Utilizing the rat mammary adenocarcinoma and Fischer bladder cell
      carcinoma cell lines, it has been shown that the i.p. administration of P1 and P2
      can produce significant differences in mean tumor diameters as compared to the
      untreated controls.

PMID- 8297149
TI  - Phloridzin and phloretin inhibition of 2-deoxy-D-glucose uptake by tumor cells in
      vitro and in vivo.
AB  - Utilizing the rat mammary adenocarcinoma and Fischer bladder cell carcinoma cell
      lines, this study demonstrated the ability of two known glucose transport
      inhibitors, phloridzin (P1) and its aglucone, phloretin (P2), to block glucose
      transport into whole viable tumor cells in vitro and tumor tissues in vivo. This
      work represents the first in a series of experiments designed to explore the
      efficacy of P1 and P2 administration in restraining tumor cell growth via the
      inhibition of glucose transmembrane transport.

PMID- 8297150
TI  - PB-100: a potent and selective inhibitor of human BCNU resistant glioblastoma
      cell multiplication.
AB  - Major drawbacks to present-day cancer chemotherapy are its intrinsic lack of
      selectivity for tumour cells, resulting in severe damage to normal rapidly
      dividing cells, and the widespread emergence of drug resistance. Here
      experimental evidence is presented demonstrating that PB-100, a beta-carboline
      alkaloid, selectively inhibits in vitro multiplication of human BCNU-resistant
      glioblastoma cells (U251), but has no effect on normal astrocyte (CRL 1656)
      multiplication. PB-100 activity is dose-dependent. In the presence of ferritin or
      CaCl2, which are highly mitogenic for glioblastoma cells, higher doses of the
      alkaloid are required to inhibit multiplication completely. PB-100 is one of
      several compounds which were selected for their specific action on cancer DNA and
      cells, together with lack of activity on normal DNA and cells. Both the
      selectivity of PB-100 and its ability to overcome drug resistance stem from its
      effect on cancer DNA secondary structure. This activity is described and
      discussed, and therapeutic applications are mentioned.

PMID- 8297151
TI  - Detection of neutral active phosphatidylcholine-specific phospholipase C in
      Friend leukemia cells before and after erythroid differentiation.
AB  - With respect to normal tissues, 31P NMR spectra of tumors usually exhibit
      elevated phosphomonoester (PME) and phosphodiester (PDE) signals, arising from
      phospholipid metabolites such as phosphocholine (PCho) and glycerophosphocholine
      (GroPCho) (and/or ethanolamine analogues). PME and PDE resonances may undergo
      significant alterations during tumor growth, at early stages of tumor response to
      treatment or following cell differentiation and maturation. The enzymatic
      mechanisms which regulate these alterations are scarcely understood. Recent
      studies on agonist-induced phosphatidylcholine (PC) hydrolysis by PC-specific
      phospholipase C (PC-plc) in cells stimulated by hormones or growth factors
      suggest the hypothesis that repeated transient activations of this enzyme may
      also contribute to the elevation of PCho levels in tumor NMR spectra. This paper
      reports the first direct evidence on neutral active PC-plc activity in a tumour
      cell system, Friend leukemia cells, either in the undifferentiated (FLC) or
      differentiated state (dFLC). Cell homogenates were incubated in the presence of
      mixed diheptanoylphosphatidylcholine/sphingomyelin unilamellar vesicles (SLUV),
      which were previously shown to represent a good substrate for bacterial plc. 31P
      NMR analyses allowed the simultaneous detection and quantification of
      phosphorylated metabolites produced in tumor cell homogenates by PC-plc activity,
      as well by enzymes active in the PC deacylation pathway. With respect to FLC,
      dFLC homogenates exhibited higher PC-plc activity and lower accumulation of a
      deacylation product, GroPCho, in agreement with the elevation in the
      [PCho]/[GroPCho] ratio, already reported in 31P NMR spectra of intact
      differentiated cells. The direct detection of PC-plc in this cell system opens
      novel biochemical interpretations on a series of oncological observations, such
      as a) transient increases in the levels of PCho and PC-derived diacylglycerols
      reported in immature or in transformed cells in response to agonist-receptor
      interactions and b) accumulation of mobile lipids in tumor cell membranes and
      tissues.

PMID- 8297152
TI  - Stromelysin-3 mRNA expression and malignancy: comparison with clinicopathological
      features and type IV collagenase mRNA expression in breast tumors.
AB  - mRNA expression of stromelysin-3 (ST3) and 72K type IV collagenase (cIVase) in 4
      human breast cancer cell lines and 55 resected breast tumors were examined using
      Northern blot analysis. In 4 cell lines ST3 was not expressed at all, while
      cIVase gene expression was detected in 3 of them. The ST3 expression was found
      more specifically in malignant tumors (39/40, 97.5%) than in benign ones (4/15,
      26.7%), although cIVase was expressed in all tumor specimens. The quantitative
      analysis showed that ST3 expression in malignancies was significantly greater
      than that in benign tumors (P = 0.0007), while cIVase expression was not (P =
      0.1381). ST3 gene expression was also closely related to the presence of lymph
      node metastasis (P = 0.047), while cIVase was not (P = 0.1091). These results
      suggest, therefore, that ST3 is expressed more specifically by stromal cells
      surrounding cancer cells than cIVase. Since ST3 mRNA expression was independent
      of the EGFR, ER and erbB2 protein expression, ST3 may be a new potent prognostic
      guide for breast carcinomas, which can detect highly malignant subpopulations.

PMID- 8297153
TI  - Genetic alteration in gastrointestinal cancer. A molecular and cytogenetic study.
AB  - We examined 16 cases of gastrointestinal cancer, of which 11 were from the colon,
      1 from the rectum, and 4 of gastric origin, cytogenetically for expression and
      for loss of heterozygosity (LOH) on chromosome 18 using Deleted Colon Cancer
      (DCC) gene. LOH on chromosome 18 with DCC probe was detected in 7 out of 11 cases
      of colon, in 4 out of 4 cases of gastric and in 1 case of rectum cancer. In all
      gastrointestinal tumors the expression of DCC gene was absent, while it was
      present in normal tissue. We also found rearrangements of chromosomes 18 (10
      cases) and 17 (9 cases), leading respectively to deletions of long and short
      arms. Other additional abnormalities were observed involving chromosomes 5, 6, 15
      and 19. The data recorded in our series differ from other authors' data in three
      respects: a high incidence of pseudodiploid chromosome number, rearrangements of
      chromosome 19 and 15, and involvement of DCC gene in the development of gastric
      cancer, as well as in colorectal cancer as previously reported.

PMID- 8297154
TI  - Comparative study of the antitumor activity of bistramides A, D and K against a
      non-small cell broncho-pulmonary carcinoma.
AB  - Bistramides A, D and K are substances extracted from the marine ascidian
      Lissoclinum bistratum Sluiter that are capable of inducing in vitro terminal
      differentiation (G1DT) of cells from a non-small cell broncho-pulmonary carcinoma
      (NSCLCN6), but present different in vitro toxicities. This study shows that only
      the least toxic bistramides D and K possess an antitumor activity. These two
      substances could be administered as a continuous treatment which would induce
      terminal differentiation of stem cells at their entry into the cell cycle,
      thereby causing their destruction.

PMID- 8297155
TI  - The effect of local anaesthetics on the thermal sensitivity of HTC cells.
AB  - Local anaesthetics caused death of HTC cells, and the order of toxicity
      (dibucaine > tetracaine > procaine) correlated with their oil:water partition
      coefficients. Cytotoxic effects of hyperthermia were enhanced by subtoxic levels
      of anaesthetics and again, their potency was related to the oil:water partition
      coefficients. DPH fluidity in plasma membranes at 37 degrees C was increased by
      dibucaine and tetracaine but not by procaine up to 5mM. At 43 degrees C, plasma
      membrane fluidity was increased by dibucaine but not by tetracaine or procaine.
      The results suggest that fluidisation of the hydrophobic core of the membrane may
      contribute to anaesthetic potentiation of heat cell death.

PMID- 8297156
TI  - Inhibition of liver microsomal cytochrome P450 activity and metabolism of the
      tobacco-specific nitrosamine NNK by capsaicin and ellagic acid.
AB  - The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone
      (NNK), present in tobacco and tobacco smoke, is metabolically activated by
      microsomal enzymes. In this study, we examined the effect of capsaicin and
      ellagic acid on the in vitro metabolism of NNK by hamster and rat liver
      microsomes. Capsaicin is the principal component of Capsicum fruits used widely
      throughout the world as a food additive. Ellagic acid, with reported
      anticarcinogenic properties, is found in various soft fruits and nuts. Both
      capsaicin and ellagic acid inhibited the major pathways of NNK-reduction, N
      pyridine oxidation and a-hydroxylation by hamster liver microsomes. Capsaicin
      inhibited NNK-reduction and a-hydroxylation and ellagic acid inhibited N
      oxidation and a-hydroxylation by rat liver microsomes. The effects of capsaicin
      and ellagic acid on isozymes of cytochrome P450 were observed in the
      hydroxylation reactions of the metabolism of the steroid hormone testosterone.
      Results of these experiments indicated that both capsaicin and ellagic acid
      strongly inhibited the constitutive enzymes CYP 2A2, 3A1, 2C11, 2B1, 2B2 and 2C6.
      This study suggests that capsaicin and ellagic acid, as naturally occurring
      dietary constituents, possess antimutagenic and anticarcinogenic properties
      through the inhibition of xenobiotic metabolizing enzymes.

PMID- 8297157
TI  - Use of a biotinyl-estradiol derivative to demonstrate estradiol-membrane binding
      sites on adherent human breast cancer MCF-7 cells.
AB  - A biotinyl-derivative of 17 beta-estradiol has been used to demonstrate a site of
      recognition and binding of estradiol located on the plasma membrane of human
      breast cancer MCF-7 cells by using the biotin/avidin-FITC system. The specificity
      of this binding has been shown by a displacement of the fluorescent label by 17
      beta-estradiol. No displacement was observed when testosterone was added.
      Quantification of this phenomenon has been shown by laser scanning cytometry
      while preserving the cells adhesiveness to their growth support as well as their
      membrane integrity. An analysis by confocal laser scanning microscopy suggested
      that the fluorescence distribution on MCF-7 cells treated with estradiol-biotin
      was on the cell periphery. The results obtained are in favour of the recognition
      and binding site of 17 beta-estradiol located on the plasma membrane of MCF-7
      cells and they would indicate that the biological activity of estradiol, among
      others, could be initiated by an interaction with the membrane.

PMID- 8297158
TI  - In vitro estradiol-sensitivity characterization of the MCF-7, ZR-75, MDA-MB-231
      and T47-D human breast neoplastic cell lines.
AB  - Even if it seems that everything has been said about the influence of estradiol
      on cell proliferation in human breast cancer cell lines such as MCF-7, T47-D, ZR
      75 and MDA-MB-231, in this study of the possible autocrine and/or paracrine role
      of 17 beta estradiol (E2) on the proliferation of human breast cancer cell lines
      we nevertheless offer some complementary information in this field of research.
      We exogenously stimulated the cell lines by the addition to the culture media of
      E2 and the anti-E2 antibody. The latter neutralizes the effects of any endogenous
      E2. The cell proliferation was assessed by means of the MTT colorimetric test. We
      thus showed that the level of sensitivity of various breast cancer cell lines to
      estradiol in terms of cell proliferation depends on the experimental schedule
      chosen. Indeed, the addition of E2 to the culture media stimulated the growth of
      the the ZR-75 and T47-D cell lines conventionally described as estrogen-receptor
      positive (ER+). For the MCF-7 cell line and the conventionally described as
      estrogen-receptor negative (ER-) MDA-MB-231 cell line, this is not the case. In
      sharp contrast, the addition to the culture media of the antibody neutralizing
      the biophysical activity of E2 sharply decreased the proliferation rate of the
      four cell lines under study. So these four cell lines in fact seem to be
      estradiol-sensitive. Thus, those which do not react to the addition of estradiol
      might use E2 in an autocrine and/or paracrine manner.

PMID- 8297159
TI  - [Urodynamics in the hands of the physician].
AB  - Urodynamic studies provide a physiological approach to a clinical practice. The
      physician is able to evaluate the relative contribution of each pathway to a
      given disease. When these investigations are performed by a clinician, he must
      avoid pseudoscientific sophistication but also simplistic interpretations. A good
      practice of urodynamics implies both rigour and simplicity.

PMID- 8297160
TI  - [Evaluation and treatment of neurogenic vesico-sphincter dysfunction].
AB  - The evaluation of neurogenic vesicosphincteric disorders is based on clinical
      examination and instrumental assessment, composed of urodynamic and perineal
      electrophysiological studies allowing a better understanding of the
      pathophysiology, aetiopathogenesis and course of the symptoms. The treatment of
      urinary symptoms, whether medical, surgical, mixed or involving various
      rehabilitation techniques, must satisfy a dual objective of individual and
      psychosocial comfort and preservation of the patient's uronephrological future.

PMID- 8297161
TI  - [Urodynamic studies in children].
AB  - Disturbances of micturition and continence in children are frequent and, in
      certain cases, urodynamic studies provide a major diagnostic contribution to the
      clinical and radiological assessment. Many investigation techniques are
      available, ranging from simple uroflowmetry to the most complex urodynamic study
      recording bladder pressure, urethral pressure and urethral sphincter
      electromyography. In children, it is essential to record abdominal pressure, to
      perfuse the bladder slowly and to be present during the examination in order to
      correctly detect any artefacts. The indication for urodynamic examination and its
      technique depend on the results of a thorough clinical assessment and useless or
      invasive examinations must be avoided. Urodynamic studies have an important role
      in the diagnosis, prognosis and treatment of neurological problems, but have a
      more variable role in functional disease, the most frequent and most extensively
      studied and in uropathies responsible for disturbances of micturition or
      continence.

PMID- 8297162
TI  - [Psychogenic dysuria].
AB  - Psychogenic urinary retention is not uncommon. Urodynamic studies demonstrate the
      absence of organicity allowing us to concentrate and define psychological causes.
      Sexual abuse is the most frequent but also, depression, hysteria and numerous
      inhibitory factors of educational origin.

PMID- 8297163
TI  - [Female urethral syndrome].
AB  - The urethral syndrome is probably the most frequent reason for urological
      consultation among women. Chronic non-specific urethritis and hypoestrogenism
      with resulting vaginal and urethral atrophy appear to be responsible. A summary
      of pathophysiology and treatment of the syndrome is presented.

PMID- 8297164
TI  - [Pharmacologic treatment of urinary dysfunctions].
AB  - After reviewing the nervous control of the lower urinary tract, the author
      defines the action of various drugs on the bladder, bladder neck, urethra (smooth
      and striated sphincter). The drugs are classified according to their stimulant or
      blocking effect on the sympathetic and parasympathetic nervous systems and alpha
      and betadrenergic receptors. Drugs acting on smooth and striated muscle fibres
      are then studied and the iatrogenic adverse effects of these drugs are mentioned.

PMID- 8297165
TI  - [Urodynamics in functional rehabilitation].
AB  - Urodynamics is used as an help to aid the diagnosis of sphincter or bladder
      dysfunction mechanisms and as an evaluation tool of drugs (tests) or retraining
      (biofeedback). The following are used: uroflowmetry sphincterometry cystometry,
      electrodiagnosis. These data are recorded simultaneously. In rehabilitation
      medicine, a special place is given to the active patient's participation during
      the examination. This allows a good approach to voluntary control and micturition
      reflex.

PMID- 8297166
TI  - [Urodynamics and perineal rehabilitation in women. Prognosis and results].
AB  - It is essential, as far as possible to be able to predict the result of perineal
      rehabilitation. It seems preferable to complete perineal testing by a clinical
      functional test for evaluation of the preventive action of voluntary perineal
      contraction in stress incontinence and to measure urethral pressure in four
      different conditions: at rest, during stress (coughing), during voluntary
      perineal contraction, and during both stress and voluntary perineal contraction.
      These tests and measures provide a better evaluation of active continence, both
      reflex and voluntary continence, and the ability of voluntary mechanisms to
      compensate for reflex mechanism during stress. It is also very important to
      estimate the results of perineal rehabilitation using a lot of objective and
      subjective tests and taking into account that only the very good results must be
      considered as successful. According to these criteria the authors estimate the
      successful results at 50% at the end of rehabilitation and only 25% in the course
      of the third year after the end of rehabilitation.

PMID- 8297167
TI  - Connection between cell adhesion and transplantations.

PMID- 8297168
TI  - Local recurrence is "not a cause of, distant metastases".

PMID- 8297169
TI  - Axonal necrosis of enteric autonomic nerves in continent ileal pouches.

PMID- 8297170
TI  - Melanoma recurrence after excision: is a wide margin justified?

PMID- 8297171
TI  - Perioperative predictors of morbidity following hepatic resection for neoplasm. A
      multivariate analysis of a single surgeon experience with 105 patients.
AB  - OBJECTIVE: Factors that predict mortality or morbidity risk in consecutive
      hepatic resections for neoplasm were examined, with controlled variables of
      surgical technique and experience. SUMMARY BACKGROUND DATA: Hepatic resection has
      become the therapy of choice for the management of metastatic or primary
      neoplasms of the liver. Although mortality for this procedure has steadily
      decreased, associated morbidity remains high. METHODS: One hundred five patients
      undergoing hepatic resection for malignancy over a 4-year period by a single
      surgeon to identify preoperative, intraoperative, or postoperative predictors of
      morbid outcomes were studied. Variables were analyzed using multiple regression
      in a stepwise, logistic model. RESULTS: Sixty-day hospital mortality was 2.8%,
      with morbidity occurring in 33%. A significant preoperative predictor of
      morbidity was serum bilirubin (p > 0.005). Notably, preoperative renal function,
      or medical illness, did not increase morbid risk. Operative variables increasing
      risk included extent of resection, blood loss, and operative time (p > 0.005).
      CONCLUSIONS: Complex hepatic resection can be performed with low mortality, and
      serum bilirubin is the single most powerful predictor of postoperative
      complication.

PMID- 8297172
TI  - Human gallstones contain pronucleating nonmucin glycoproteins that are
      immunoglobulins.
AB  - OBJECTIVE: Pronucleating nonmucin glycoproteins in human cholesterol and black
      gallstones were isolated and identified. SUMMARY BACKGROUND DATA: Gallbladder
      bile contains nonmucin glycoproteins that are pronucleating of cholesterol
      monohydrate crystals. Little is known about the presence or activity of these
      proteins within gallstones. METHODS: Nonmucin glycoproteins were isolated from
      single cholesterol (n = 8), multiple cholesterol (n = 8), and black pigment (n =
      8) gallstones by concanavalin A lectin-affinity chromatography. The proteins were
      separated by sodium dodecyl sulfate gradient electrophoresis. Western blot
      analysis was performed for Fab immunoglobulin fragments, and heavy chains from
      the immunoglobulin G, A, E, and M subclasses. A crystal observation time assay
      was performed on the combination of isolated nonmucin glycoproteins from
      gallstones and isolated Fab fragments. RESULTS: Nonmucin glycoproteins of
      molecular weights 10, 15, 17, 22, 28, and 208 kD were identified in gallstones.
      These six nonmucin glycoproteins shortened the crystal observation time by more
      than 50% (p < 0.01) compared with model bile. Western blot analysis confirmed the
      identity of the 22- and 28-kD proteins as immunoglobulin Fab fragments. These
      were seen in all gallstones, irrespective of the gallstone type. The isolated Fab
      28-kD fragment from the gallstones of 23 patients shortened the extrapolated
      crystal observation time by 78% (p < 0.01). However, commercially available Fab
      fragments had no effect on either cholesterol crystal appearance or growth.
      CONCLUSIONS: Nonmucin glycoproteins that are pronucleating for cholesterol
      monohydrate crystals are also found in human cholesterol and black pigment
      gallstones. Fab immunoglobulin fragments were found in all gallstones
      irrespective of the gallstone type. Fab immunoglobulin fragments from gallstones
      shortened the crystal observation time but not crystal growth or total crystal
      content compared with model bile or commercially available Fab fragments. These
      data suggest that an antigen-immune (Fab) complex may contribute to cholesterol
      crystal function.

PMID- 8297173
TI  - A 15-year experience of injection sclerotherapy in adult patients with
      extrahepatic portal venous obstruction.
AB  - OBJECTIVE: The authors report a 15-year experience with injection sclerotherapy
      in the management of adult and teenage patients with esophageal varices due to
      extrahepatic portal venous obstruction (EHPVO). SUMMARY BACKGROUND DATA:
      Extrahepatic portal venous obstruction is an uncommon cause of esophageal varices
      and is associated with normal liver function. Effective control of variceal
      bleeding is the major factor influencing survival. The results of surgery have
      been unsatisfactory, and therefore, more conservative management policies have
      been adopted. METHODS: Fifty-five patients with proven EHPVO underwent repeated
      injection sclerotherapy via either a modified rigid esophagoscope under general
      anaesthesia or a fiber-optic endoscope under light sedation, using ethanolamine
      oleate as the sclerosant. RESULTS: Esophageal varices were eradicated in 44
      patients after a median number 6 injections (range 1-17) over a mean of 12.5
      months (range 1-48). The mean follow-up was 6.8 years (range 1.1-14.6 years).
      Eleven patients were admitted on eighteen occasions with bleeding from esophageal
      varices before eradication and there were seven bleeding episodes in six patients
      from recurrent varices after initial eradication. Complications related to
      sclerotherapy included injection site leak (6), stenosis (11) and mucosal
      ulceration (32) during 362 injection sclerotherapy episodes. Four patients died
      during the study period. CONCLUSIONS: Injection scelotherapy is the treatment of
      choice in most patients with EHPVO.

PMID- 8297174
TI  - Adhesion molecules and transplantation.
AB  - OBJECTIVE: Accessory adhesion molecules are thought to influence the first
      interaction between host leukocytes and graft vascular endothelial cells. Their
      role in transplantation is reviewed. SUMMARY: Adhesion molecules have been
      divided into three major families: the selectins, the integrins, and the
      immunoglobulin superfamily. Selectins are small proteins that mediate the first
      contact between stimulated endothelial cells and leukocytes. Integrins interact
      with cytoskeletal components of cells, presumably coordinating extracellular
      stimuli with cytoskeleton dependent actions, such as motility, shape change, and
      phagocytic responses. Members of the immunoglobulin superfamily are structurally
      homologous, although they do not necessarily share similar functions. They are
      involved in T-cell proliferation and intracellular events. METHODS: Various
      groups of investigators have studied the influence and expression of adhesion
      molecules following transplantation. The authors of this article have reviewed
      and summarized the available literature. RESULTS: Many different adhesion
      molecules are up-regulated during the rejection event. Treatment of transplant
      recipients with monoclonal antibodies against accessory molecules, such as
      leukocyte function associated antigen 1 (LFA-1) and intercellular adhesion
      molecule 1 (ICAM-1), has resulted in either a prolongation of transplant survival
      or the induction of tolerance in some models. Other interventions are under
      study. CONCLUSION: By mediating the initial leukocyte/endothelial cell
      interactions, adhesion molecules may play an important role in graft rejection,
      mediation of infiltration into the graft, and dissemination of the antigenic
      message to the lymphoid tissues of the host. Future studies will have to deal not
      only with conceptualizing their function and mechanisms of action, but also with
      manipulating their interrelationships to the benefit of the graft recipient.

PMID- 8297175
TI  - The incidence, timing, and management of biliary tract complications after
      orthotopic liver transplantation.
AB  - OBJECTIVE: This study analyzed the incidence and timing of biliary tract
      complications after orthotopic liver transplantation (OLTx) in 1792 consecutive
      patients. These results were then compared with those of previously reported
      series. Finally, recommendations were made on appropriate management strategies.
      SUMMARY BACKGROUND DATA: Technical complications after OLTx have a significant
      impact on patient and graft survival. One of the principal technical advances has
      been the standardization of techniques for biliary reconstruction. Nonetheless,
      biliary complications still occur. A 1983 report from the University of
      Pittsburgh reported biliary complications in 19% of all transplants, and an
      update in 1987 reported biliary complications in 13.2% of transplants. METHODS:
      The medical records of all patients who underwent liver transplantation and were
      hospitalized between January 1, 1988 and July 31, 1991 were reviewed. The case
      material consisted of the medical records of 217 patients treated for 245 biliary
      complications. RESULTS: Primary biliary continuity was established by either
      choledochocholedochostomy over a T-tube (C-C, n = 129) or a Roux-en-Y
      choledochojejunostomy with an internal stent (C-RY, n = 85). The overall
      incidence for biliary complication in this large series was 11.5%. Strictures (n
      = 93) and bile leak (n = 58) were the most common complications (69.6%). Most
      biliary complications (n = 143, 66%) occurred within the first 3 months after
      surgery. In general, leaks occurred early, and strictures developed later. Bile
      leaks were equally frequent in both C-C and C-RY (27.1% and 25.9%, respectively);
      strictures were more common after a C-RY type of reconstruction (36.4% and 52.9%,
      respectively). Twenty-one patients died, an incidence of 9.6%. Fifteen of the 21
      biliary-related deaths were among patients treated for rejection before the
      recognition of biliary tract pathologic findings. CONCLUSIONS: Progress has been
      made on improving the results of biliary reconstruction after OLTx. Nonetheless,
      patients continue to experience biliary complications after OLTx, and these
      complications cause considerable loss of grafts and life. If significant
      additional improvement in patient and graft survival are to be obtained, the
      technical performance of OLTx must continue to improve.

PMID- 8297176
TI  - Study of donor-recipient liver size match for transplantation.
AB  - OBJECTIVE: This animal experiment investigated the donor-recipient liver size
      match for safe liver transplantation. BACKGROUND: In spite of refinements in
      surgical techniques in reduced liver transplantation, the liver size disparity
      remains one of the most common complications in pediatric patients. Optimal size
      matching remains unknown. METHODS: The experiment compared eight groups of liver
      transplanted rats with designated ratios of donor and recipient liver weights.
      Donor livers harvested from rats weighing 420-520 g were reduced to the
      designated size by liver lobectomy and implanted in rats weighing 170-240 g. Bile
      secretion and serum aspartate aminotransferase (AST) activities in groups 2, 4,
      and 6 were studied after surgery. RESULTS: Stepwise increase of the ratio of
      donor and recipient liver weights from 1.04:1 in group 4 to 1.26:1 in group 3,
      1.56:1 in group 2, and 2.04:1 in group 1 caused stepwise decrease of survival
      rates from 83.3% to 66.7%, 16.7%, and 0%, respectively. Stepwise decrease of the
      ratio from 1.04:1 in group 4 to 0.79:1 in group 5, 0.53:1 in group 6, 0.35:1 in
      group 7, and 0.24:1 in group 8 also caused stepwise reduction of survival rates
      from 83.3% to 66.7%, 50%, 0%, and 0% in each group. CONCLUSION: The range of
      ratios of donor and recipient liver weights for successful rat liver
      transplantation is from 0.53:1 to 1.26:1. Increase and decrease of ratios of
      donor-recipient liver weights from equal size do not increase the recipient
      survival rates. Recipients of reduced donor liver weights tend to have a higher
      survival rate than recipients of increased donor liver weights.

PMID- 8297177
TI  - The natural history of surgically treated primary adenocarcinoma of the appendix.
AB  - OBJECTIVE: The aim of this investigation was to determine the prognostic
      variables and optimal surgical procedure for patients with adenocarcinoma of the
      appendix. SUMMARY BACKGROUND DATA: Primary adenocarcinoma of the appendix is a
      rare malignancy that constitutes less than 0.5% of all gastrointestinal
      neoplasms. However, the prognostic factors and the preferred surgical procedure
      and outcome are poorly understood. METHODS: The authors reviewed their
      institutional experience from 1976 to 1992 in treating 94 consecutive patients
      with primary adenocarcinoma of the appendix. Patients with carcinoid tumors or
      those in whom the diagnosis of primary cecal cancer could not be ruled out were
      excluded from the study. RESULTS: Fifty-two (55%) patients had the mucinous
      variety, of which 22 had pseudomyxoma peritonei; the other 45% had the colonic
      and adenocarcinoid types of tumor. The most common presentation was that of acute
      appendicitis. Interestingly, in no patients was the correct diagnosis made before
      surgery, and it was entertained intraoperatively in only 30 patients (32%). The
      cure 5-year survival rate was 55%, but it varied with stage (A, 100%; B, 67%; C,
      50%; and D, 6%; p < 0.01) and with grade (I, 68%, and III, 7%; p < 0.01).
      Patients with the mucinous type had a better prognosis than those with the
      colonic type (p < 0.01). The survival rate was superior after right hemicolectomy
      versus appendectomy alone (68% vs. 20%, p < 0.001). Right hemicolectomy performed
      as a secondary procedure resulted in the upstaging of 38% of the patients'
      tumors. A second primary malignancy occurred in 33 patients (35%), of which 17
      were located in the gastrointestinal tract. CONCLUSIONS: Primary adenocarcinoma
      of the appendix should be treated by right hemicolectomy, even if it is a
      secondary procedure. Surveillance for synchronous or metachronous tumors,
      especially in the gastrointestinal tract, is warranted.

PMID- 8297178
TI  - A role for calcitonin gene-related peptide in protection against gastric
      ulceration.
AB  - OBJECTIVE: The goal of this investigation was to determine the role of calcitonin
      gene-related peptide (CGRP) in gastric mucosal resistance to ulceration. SUMMARY
      BACKGROUND DATA: CGRP is a 37-amino acid peptide found in the peripheral ends of
      afferent gastric neurons. CGRP is known to inhibit acid secretion, stimulate
      mucosal blood flow, and stimulate release of somatostatin. METHODS: The release
      of CGRP in response to intragastric and intra-arterial administration of
      capsaicin in the isolated, vascularly perfused rat stomach was measured by
      radioimmunoassay. The molecular forms of CGRP released were analyzed by gel
      filtration chromatography. The effect of intravenous CGRP or intragastric
      capsaicin on gastric ulceration induced by 100 mmol/L HCl and indomethacin was
      studied in intact and endogenous CGRP-depleted rats. RESULTS: Intra-arterial
      capsaicin (concentration range, 10(-7) to 10(-5) mol/L) stimulated a prompt and
      sustained release of immunoreactive CGRP, of which 84% coeluted with rat 1-37
      CGRP I by gel filtration. Intragastric capsaicin (range, 10(-5) to 10(-4) mol/L)
      failed to release CGRP into the vascular perfusate. In intact rats, intragastric
      capsaicin (10(-6) mol/L) or intravenous CGRP I (10 micrograms/kg/hr) reduced the
      number and area of mucosal lesions caused by HCl and indomethacin compared with
      the findings in control rats. Rats depleted of endogenous CGRP were more
      susceptible to gastric ulceration than were normal rats. Intragastric capsaicin
      failed to protect the mucosa of CGRP-depleted rats, whereas exogenous intravenous
      CGRP was effective. CONCLUSIONS: These data support the hypothesis that CGRP
      released from gastric enteric neurons mediates gastric mucosal resistance to
      ulceration by noxious agents.

PMID- 8297179
TI  - Adult skin wounds in the fetal environment heal with scar formation.
AB  - OBJECTIVE: This study investigated the influence of the fetal environment on the
      healing characteristics of adult skin. SUMMARY BACKGROUND DATA: The remarkable
      ability of the fetus to heal without scarring is poorly understood. The unique
      qualities of fetal wound healing may be caused by the fetal environment, the
      fetal tissues, or a combination of both. There are numerous differences between
      the prenatal and postnatal environments that may play a role in the unique fetal
      response to injury. METHODS: Full-thickness adult sheep skin was transplanted
      onto the backs of 60-day-gestation fetal lambs (term, 145 days of gestation). The
      adult skin grafts were thus perfused by fetal blood and bathed in amniotic fluid.
      Previous work has demonstrated that, before midgestation, fetal lambs do not
      reject allogenic skin grafts. Forty days later (100 days of gestation),
      incisional wounds were made on both the adult skin graft and the adjacent fetal
      skin. The wounds were harvested 14 days postwounding and analyzed by both light
      microscopy and immunohistochemical testing using antibodies to collagen types I,
      III, and VI. RESULTS: The wounds in the adult skin grafts healed with scar
      formation. This observation contrasts strongly with the scarless healing of the
      incisional fetal skin wounds. CONCLUSIONS: This study suggests that scarless
      fetal skin healing properties are intrinsic to fetal skin and are not primarily
      the result of the fetal environment.

PMID- 8297180
TI  - Increased cardiac endocrine activity after common bile duct ligation in the
      rabbit. Atrial endocrine cells in obstructive jaundice.
AB  - OBJECTIVE: This study investigated the pathogenesis of water and sodium
      metabolism derangements in obstructive jaundice. SUMMARY BACKGROUND DATA:
      Obstructive jaundice is associated with hypodipsia, depletion of extracellular
      water, alterations of the water and sodium regulating hormones, and an increased
      incidence of renal failure. Plasma atrial natriuretic factor (ANF) increases
      after common bile duct ligation in the rabbit. The present study was designed to
      investigate ANF-secreting cardiac atrial cells in this animal model. METHODS:
      Plasma ANF and the percentage of atrial cells staining for ANF were determined in
      jaundiced and sham-operated rabbits at 24 (group OJ-24, n = 11; group SO-24, n =
      5) and 72 hours (group OJ-72, n = 11; group SO-72, n = 5) after surgery. The
      atrial ANF content was also determined. RESULTS: Plasma ANF was higher in
      jaundiced animals than in controls both at 24 (63 +/- 44 fmol/mL vs. 17 +/- 10
      fmol/mL, p < 0.02) and at 72 hours (73 +/- 49 fmol/mL vs. 12 +/- 11 fmol/mL). In
      the two OJ groups, the percentage of positive ANF cells per 200-power field in
      the right atrial appendage was higher than in the SO groups both at 24 (62 +/-
      11% vs. 31 +/- 12%, p < 0.003) and at 72 hours (56 +/- 18% vs. 31 +/- 12%, p <
      0.01). Similar results were obtained in the right auricular wall. The percentage
      of positive ANF cells was significantly higher in the left atrium in which
      significant differences between the OJ and SO groups were also noted. The right
      atrial ANF content was higher in the OJ than in SO groups (437 +/- 323 pmol/mg of
      protein vs. 83 +/- 44 pmol/mg of protein). CONCLUSIONS: Cardiac endocrine
      activity is increased in experimental obstructive jaundice. ANF may be involved
      in the pathogenesis of the renal and water and sodium metabolic disturbances
      present in this disease.

PMID- 8297181
TI  - Role of spinal afferents and calcitonin gene-related peptide in the postoperative
      gastric ileus in anesthetized rats.
AB  - OBJECTIVE: The object of this study was to investigate the mechanisms of
      postoperative gastric ileus in an experimental model of abdominal surgery in
      anesthetized rats. SUMMARY BACKGROUND DATA: Sensory neurons partly mediate
      postoperative gastric ileus. Among other neuropeptides, sensory neurons contain
      calcitonin gene-related peptide (CGRP) and release CGRP in response to noxious
      stimulation. Because CGRP inhibits gastric motility, it was hypothesized that
      abdominal surgery stimulates sensory neurons, which then releases CGRP, thereby
      inhibiting gastric motility. METHODS: Postoperative ileus was induced by
      abdominal surgery. Gastric corpus motility was measured by an intragastric
      catheter. CGRP action was blocked by CGRP immunoneutralization or by a CGRP
      receptor antagonist. Spinal sensory neurons were ablated by application of a
      sensory neurotoxin (capsaicin) to the celiac and superior mesenteric ganglia.
      RESULTS: Abdominal surgery decreased gastric corpus motility in the first 5
      minutes after abdominal surgery by 59 +/- 5% and by 24 +/- 4% during the 1st
      postoperative hour. Capsaicin pretreatment of the celiac and superior mesenteric
      ganglia, CGRP immunoneutralization, or CGRP receptor antagonism reversed the
      postoperative decrease in gastric corpus motility during the 1st postoperative
      hour by 50%, 100%, and 59%, respectively. CONCLUSIONS: These data indicate that
      spinal sensory neurons and CGRP partly mediate postoperative gastric ileus. CGRP
      may be released from spinal sensory neuron terminals in the celiac and superior
      mesenteric ganglia as part of an extraspinal intestinogastric inhibitory reflex
      activated by abdominal surgery.

PMID- 8297182
TI  - Studies on the muscle-paralyzing components of the juice of the banana plant.
AB  - The stem juice of the banana plant (Musa species) has been used as an arrow
      poison by African tribesmen. Lyophilized, partially purified extracts of the
      juice augment and then block both directly and indirectly evoked contractions of
      the mouse diaphragm. We have isolated, purified and determined the chemical
      composition of the active ingredients, and characterized their pharmacological
      activity. The lyophilized sample was extracted with a methanol-water (MeOH-H2O)
      (50/50) mixture and vacuum filtered. The filtrate was rotary evaporated and
      crystallized in a MeOH-H2O mixture to yield potassium nitrate crystals (melting
      point 332-334 degrees C). The filtrate was concentrated and chromatographed over
      Sephadex LH-20 gel using MeOH-H2O (40/60) as the eluent. The active component was
      found to be magnesium nitrate crystals (melting point 87-89 degrees C). In the
      mouse isolated phrenic nerve-hemidiaphragm preparation, the pharmacological
      profile of the first component was similar to that for authentic potassium
      nitrate which augments in low concentrations, and in higher concentrations
      augments, and then blocks both directly evoked muscle contraction the
      neuromuscular transmission. The second component had a profile of activity
      similar to that for authentic magnesium nitrate which only blocks neuromuscular
      transmission. It can be concluded that the two major active principles in the
      banana stem juice are potassium nitrate and magnesium nitrate.

PMID- 8297183
TI  - Effects of buspirone on the resistance, development and passive transfer of
      immunity to Listeria monocytogenes in mice submitted to stress.
AB  - Mice exposed to a chronic auditory stressor and treated chronically with
      buspirone (1 mg/kg) showed a reduction in stress-induced suppression of the
      resistance and development of immunity to Listeria monocytogenes. Attempts to
      passively transfer immunity with spleen cells were also performed. Stressed,
      immunized mice had a reduced capacity to transfer immunity passively to
      nonimmunized mice and buspirone was found to partially suppress this inhibitory
      effect of stress.

PMID- 8297184
TI  - Anti-hypoxic and anti-ischemic actions of indeloxazine hydrochloride and its
      optical isomers: possible involvement of cerebral energy metabolism.
AB  - We evaluated the anti-hypoxic and anti-ischemic actions of indeloxazine
      hydrochloride ((+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride, YM-08054)
      in comparison with its optical isomers and several selective monoamine uptake
      inhibitors in mice. The effects of indeloxazine on both cerebral energy
      metabolism in normal mice and local cerebral glucose utilization in normal rats
      were also studied. Indeloxazine and its (-)-isomer, with both serotonin and
      norepinephrine uptake inhibitory actions, and its (+)-isomer, with a serotonin
      uptake inhibitory action, prolonged the survival time of mice subjected to
      nitrogen gas and the gasping duration in decapitated mice. Indeloxazine and its
      (+)-isomer were approximately 3-10 times more potent than the (-)-isomer with
      regard to their anti-hypoxic and anti-ischemic activities. Selective
      norepinephrine uptake inhibitors such as maprotiline and viloxazine, and
      selective serotonin uptake inhibitors such as citalopram, alaproclate and
      zimeldine, did not show anti-hypoxic properties. On the other hand, amantadine, a
      selective dopamine uptake inhibitor, and amitriptyline, a tricyclic
      antidepressant with anticholinergic properties, significantly shortened the
      survival time in hypoxic mice. In biochemical studies, increases in brain ATP and
      glucose levels without affecting lactate level in mice and an elevation in local
      cerebral glucose utilization in 10 brain regions involving the frontal cortex in
      rats were observed after administration of indeloxazine. These results suggest
      that indeloxazine and its optical isomers possess anti-hypoxic and anti-ischemic
      actions distinct from those of typical monoamine uptake inhibitors, and that
      these effects of indeloxazine may be due, at least in part, to a facilitation of
      cerebral energy metabolism.

PMID- 8297185
TI  - Influence of pretreatment with phenytoin, lidocaine and quinidine on the
      cardiodynamic and electrophysiological effects of ouabain in the cat heart-lung
      preparation.
AB  - The effect of pretreatment with phenytoin (diphenylhydantoin), lidocaine, and,
      for comparison, quinidine, on the doses of ouabain which produce a maximal
      inotropic effect, onset of arrhythmias and cardiac arrest, was explored in the
      cat heart-lung preparation. Ouabain was administered as an infusion (0.5
      micrograms/min) either alone or after treatment with phenytoin (0.095 +/- 0.012
      mM), lidocaine (0.090 +/- 0.004 mM) or quinidine (0.028 +/- 0.006 mM) and the
      cardiodynamic and electrophysiological changes monitored. Phenytoin, lidocaine
      and quinidine were administered in doses which were maximally tolerated by the
      preparations to ensure full effect, as evidenced by early cardiac depression.
      Ouabain alone produced a maximal increase in contractility prior to the
      development of arrhythmias at a blood concentration of 0.212 +/- 0.014 microM,
      onset of arrythmias at 0.227 +/- 0.015 microM, stable ventricular tachycardia at
      0.269 +/- 0.010 microM and cardiac arrest at 0.342 +/- 0.014 microM. Pretreatment
      with phenytoin or lidocaine did neither modify these values nor change the
      pattern of the arrhythmias or the terminal cardiac event. Pretreatment with
      quinidine prevented the development of ventricular extrasystoles and aberrant
      ventricular conduction, which were the earliest arrhythmias in all other series.
      It also made the preparations develop stable ventricular tachycardia at an
      ouabain blood concentration of 0.246 +/- 0.007 microM, which was not
      significantly different from the concentration at which early arrhythmias were
      noted in the other series. In addition, quinidine decreased the dose of ouabain
      producing cardiac arrest by 13% but did not modify the terminal event.
      Pretreatment with phenytoin, lidocaine and quinidine did not affect the
      electrocardiographic pattern, but at the maximal increase in contractility with
      ouabain prior to the development of arrhythmias, the PR interval increased to
      comparable limits with ouabain alone and ouabain after quinidine and lidocaine.
      However, with ouabain after phenytoin, this increase was 61% less than that with
      ouabain alone and 31% less than that with ouabain after quinidine. Ouabain given
      alone or after phenytoin, lidocaine or quinidine produced comparable maximal
      effects on dp/dt, -dp/dt and left atrial pressure. It may be concluded that
      pretreatment with phenytoin and lidocaine does not modify the maximal inotropic
      dose of ouabain prior to the development of arrhythmias, the arrhythmogenic dose
      or the dose producing cardiac arrest, and that phenytoin partly counters the
      ouabain-induced depression of AV conduction. Quinidine has an additive effect on
      the ouabain-induced depression of AV conduction, prevents the ouabain-induced
      increase in idioventricular rhythm responsible for extrasystoles but not that
      responsible for ventricular tachycardia, and reduces the dose of ouabain
      producing cardiac arrest.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8297186
TI  - Interactions of indomethacin with central GABA systems.
AB  - Neurochemical studies showed that indomethacin is a noncompetitive inhibitor of
      the mouse cortical synaptosomal uptake of [3H]GABA with a Ki of 0.7 mM.
      Indomethacin also displaced [3H]flunitrazepam and [3H]GABA binding to washed
      cortical membranes in a competitive manner with IC50 values of 0.18 and 0.55 mM,
      respectively. It binds to the benzodiazepine receptors with the same
      characteristics as an inverse agonist and to the GABAA receptors as an
      antagonist. Behavioral studies showed that indomethacin dose-dependently
      increased the durations of loss of righting reflex induced by either diazepam or
      pentobarbitone, decreased rota-rod treading times and effectively prevented
      generalized seizures induced by pentylenetetrazole, bicuculline, methyl-6,7
      dimethoxy-4-ethyl-beta-carboline-3-carboxylate or maximal electroshock treatment.
      It is concluded that these effects of indomethacin are probably a result of GABA
      uptake inhibition. The present findings may explain some side effects of
      indomethacin on the central nervous system, such as impairment of psychomotor
      functions.

PMID- 8297187
TI  - Persistent sodium currents induced by anthopleurin-A and their relationship to
      early afterdepolarizations in ventricular myocytes.
AB  - Prolonged Na+ current inactivation was induced in neonatal rat ventricular
      myocytes by exposure to Anthopleurin-A (80-240 nM). In control whole-cell voltage
      clamp recordings, prolonged Na+ current inactivated mono-exponentially from peak
      with time constant, tau h, averaging 1.5 msec +/- 0.2 msec at -30 mV and peak
      current averaging 0.7 +/- 0.3 nA (n = 10). Steady state inactivation was complete
      at -50 mV and there was little or no overlap of prolonged Na+ current
      inactivation and activation processes. One to 3 minutes following exposure to
      Anthopleurin-A, the rate of inactivation slowed, with tau h increasing to 21 +/-
      5 msec at -30 mV, and peak prolonged Na+ current increasing to 1.3 +/- 0.5 nA (n
      = 10). Steady state inactivation was shifted in a positive direction, and
      complete inactivation did not occur even at +10 mV. Persistent inward currents
      were thus induced by Anthopleurin-A. They were most prominent at depolarizations
      slightly above threshold for activation and were selectively blocked by lidocaine
      (60 microM). Action potentials were prolonged by Anthopleurin-A, especially at
      slow stimulation rates, and were accompanied by early afterdepolarizations. The
      correlation between persistent inward currents and early afterdepolarizations, in
      terms of voltage dependence, appearance and pharmacology, suggests a possible
      causal role for persistent Na+ currents in this model of early
      afterdepolarizations.

PMID- 8297188
TI  - Effect of 7-oxo-PGI2 on myocardial infarct size and role of oxygen radicals in
      its protective effect.
AB  - The ability of the prostacyclin analogue 7-oxo-PGI2 to inhibit infarct size in in
      vivo rat heart was assessed. Anaesthetized rats were subjected to coronary artery
      ligation for 72 hours and infarct size was measured macroscopically using
      staining with triphenyl tetrazolium chloride. Systolic blood pressure and
      electrocardiogram were monitored. 7-oxo-PGI2 (50 micrograms/kg, i.p.),
      administered 30 minutes before or after coronary artery ligation, markedly
      reduced infarct size and loss of R wave. It did not, however, influence the
      changes of systolic blood pressure and heart rate in these animals. In addition,
      7-oxo-PGI2, both in vitro and in vivo, inhibited rat PMN-evoked and luminol
      enhanced chemiluminescence and markedly reduced the increase in serum
      malonyldialdehyde levels occurring after coronary artery ligation. The capacity
      of 7-oxo-PGI2 to impair the generation of oxygen free radicals from PMN cells,
      which reach the site of ischaemic injury through the limited collateral flow
      available in rat myocardium, may be responsible for its beneficial effect on
      ischaemic myocardial injury.

PMID- 8297190
TI  - Myocardial infarction with angiographically normal coronary arteries. A personal
      perspective.

PMID- 8297189
TI  - Effects of the angiotensin-converting enzyme inhibitor quinapril on renal
      function in rats.
AB  - Angiotensin-converting enzyme inhibitors induce hypertrophy of renal
      juxtaglomerular cells in laboratory animals, and, in some studies, also produced
      renal tubular lesions. The objective of the present study was to evaluate the
      effects of the new angiotensin-converting enzyme inhibitor quinapril on renal
      function in normotensive rats. Male rats were dosed orally with quinapril at 0
      (vehicle control) or 400 mg/kg for 1, 3, 8, 17 or 29 days. This dose of quinapril
      is more than 1000-fold greater than the effective antihypertensive dose in rats.
      Parameters of renal function were measured approximately 24 hours after dosing in
      order to minimize interference from acute pharmacologically mediated effects.
      Mean arterial blood pressure was only mildly affected at this time: 126.7 +/- 6.0
      and 100.0 +/- 8.7 mm/Hg (mean +/- S.E.; day 29) for the control and quinapril
      treated animals, respectively. Microscopic analysis of kidney tissue showed
      pronounced juxtaglomerular cell hypertrophy and hypergranularity in the quinapril
      treated animals. These changes were first observed on day 7 and reached a maximum
      response by day 14. There were no morphologic changes in renal tubules. Quinapril
      had no significant effect on serum biochemistry parameters (electrolytes, urea
      nitrogen, creatinine). Urine output in quinapril-treated animals was increased
      65% to 197% over controls during the course of the study and correlated with
      increased water consumption (r = 0.96). Urine osmolality was reduced 31% to 55%
      on days 8, 17 and 29. However, except for minimal reductions (< 15%) on day 8,
      there were no significant effects of quinapril on total (24 hour) urinary
      excretion of electrolytes or creatinine. There were also minimal effects of
      quinapril on direct measurements of renal function in anesthetized animals. Mean
      values (+/- S.E.) for control and quinapril-treated animals on day 29 were,
      respectively: glomerular filtration rate: 2.93 +/- 0.37 and 2.70 +/- 0.53 ml/min;
      effective renal plasma flow: 11.14 +/- 2.06 and 11.22 +/- 2.35 ml/min; effective
      renal tubular secretion: 267 +/- 63 and 261 +/- 106 micrograms/min; filtration
      fraction: 27.1 +/- 2.5 and 24.0 +/- 0.4%; and fractional sodium excretion: 0.25
      +/- 0.04 and 0.34 +/- 0.04%. There were also no significant differences between
      control and quinapril-treated animals when the above parameters were measured
      following plasma volume expansion on day 29. The results show that quinapril had
      no adverse effects on renal function in rats when administered at a
      suprapharmacological dose for up to 4 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8297191
TI  - Professional courtesy then and now.

PMID- 8297192
TI  - Myocardial infarction with angiographically normal coronary arteries.
AB  - More than 30 years ago, when the techniques and indications for coronary
      arteriography were being defined, the entity of myocardial infarction with
      angiographically normal coronary arteries (MINC) was first reported. These first
      reports already noted that the few patients with MINC tended to be different from
      the much larger group of individuals with myocardial necrosis and coronary
      atherosclerosis. Since these early case reports and subsequent small collected
      series, there have been significant advances in our understanding of the
      pathophysiologic features of acute myocardial infarction. This review seeks to
      reexamine MINC in light of this new information.

PMID- 8297193
TI  - Remedial medical education.
AB  - Continuing medical education plays an essential role in efforts to improve
      physician performance. This article deals with remedial or personalized physician
      education. The experience of selected institutions and state organizations that
      have and/or continue to provide such remedial education is reviewed. The emphasis
      of remedial or focused physician education is educational enhancement, not
      suspension or revocation of license.

PMID- 8297194
TI  - The international normalized ratio. A guide to understanding and correcting its
      problems.
AB  - With the increasing use of the international normalized ratio (INR) to monitor
      warfarin therapy, a number of problems with prothrombin time (PT) testing have
      been identified that have led some laboratory physicians to question the
      reliability of the INR. This is ironic, because it was the introduction of the
      INR system that brought to light some of the long-standing problems with the
      technique of PT monitoring. However, these problems are not insurmountable if a
      compromise can be reached between the expectations of laboratory physicians and
      of clinicians. Thus, the laboratory physician seeks a perfect assay system, which
      in the case of the INR is unattainable at present, because of differences in PT
      reagents and methods. In contrast, the clinician is satisfied with a system of
      monitoring that provides safe and effective warfarin dosing. This goal can be
      achieved provided that certain details of PT testing are observed. In this
      communication, which is directed to practicing clinicians, the potential problems
      with the INR system are discussed, their clinical relevance is critically
      reviewed, and solutions are offered.

PMID- 8297195
TI  - A noninvasive strategy for the treatment of patients with suspected pulmonary
      embolism.
AB  - BACKGROUND: Pulmonary embolism has historically presented a formidable diagnostic
      problem because of the nonspecificity of the clinical findings associated with
      this disorder and the diagnostic uncertainties and challenges presented by both
      ventilation-perfusion lung scanning and pulmonary angiography. We have reported
      previously that serial noninvasive leg testing provides a practical noninvasive
      alternative to pulmonary angiography in patients with non-high probability
      (nondiagnostic) lung scans and adequate cardiorespiratory reserve. We have
      reevaluated this observation prospectively to (1) confirm or refute our original
      observation in an independent cohort and (2) to increase the numbers sufficiently
      to provide narrow confidence limits for the observed outcomes. METHODS: A
      prospective comparative study in 1564 consecutive patients with suspected
      pulmonary embolism who underwent ventilation-perfusion lung scanning and
      objective testing for proximal-vein thrombosis. RESULTS: On long-term follow-up
      of 627 patients with the following characteristics: (1) abnormal, nondiagnostic
      lung scans, (2) not taking anticoagulant therapy, and (3) serial noninvasive test
      results negative for proximal-vein thrombosis, only 12 patients (1.9%; 95%
      confidence limits, 0.8% to 3.0%) had venous thromboembolism. By comparison,
      venous thromboembolism on follow-up occurred in four (0.7%) of 586 patients (95%
      confidence limits, 0.02% to 1.3%) with normal lung scans in whom anticoagulant
      therapy was withheld and in eight (5.5%) of 145 patients (95% confidence limits,
      1.8% to 9.2%) with high probability lung scans who received anticoagulant
      therapy. CONCLUSIONS: Our findings indicate that the clinician has a practical
      noninvasive strategy in patients with adequate cardiorespiratory reserve and
      nondiagnostic lung scans that (1) avoids pulmonary angiography, (2) identifies
      patients with proximal-vein thrombosis who require treatment, and (3) avoids the
      need for treatment and further investigation in the majority of patients.

PMID- 8297196
TI  - Urinary tract infections with low and high colony counts in young women.
      Spontaneous remission and single-dose vs multiple-day treatment.
AB  - BACKGROUND: The aim of this study was to test whether the spontaneous cure rate
      is higher in dysuric women with low urinary colony counts (10(2) to 10(4) colony
      forming units [cfu] per milliliter) than in women with high colony counts (> or =
      10(5) cfu/mL) and whether the response of patients with low colony counts to
      single-dose treatment is better than those with high colony counts. METHODS:
      Dysuric women underwent a clinical interview, examination, urine culture, and
      microscopic examination of urine, and were asked to postpone treatment for 2
      days. At that time, the urine tests were repeated. Women with bacterial urinary
      tract infection were randomized to a group given a single dose of 1200 mg of
      norfloxacin and to a group treated with 400 mg of norfloxacin twice daily for 7
      days. Cure rates were tested at 1 and 5 weeks after treatment. RESULTS: Of 146
      women with urinary tract complaints, 113 (25 patients with sterile urine
      cultures, 21 with low colony counts, and 67 with high colony counts) agreed to
      postpone antibiotic treatment. Two days after the initial urine culture, only one
      patient with a low initial colony count had a sterile urine culture (5%, 95%
      confidence interval, 0% to 14%); and 10 patients (48%, 95% confidence interval,
      27% to 69%) had a colony count of 10(5) cfu/mL or more. The rate of spontaneous
      cure in women with high initial colony count was 7%, 95% confidence interval, 1%
      to 13%. One week after treatment, the cure rates were 48 (84%) of 57 patients
      given single-dose treatment vs 49 (98%) of 50 patients treated for 7 days. Five
      weeks after treatment the rates were 63% and 83%, respectively. The efficacy of
      single-dose treatment in patients with low urinary counts were similar to those
      with high counts, and less than that achieved by 7 days of treatment.
      CONCLUSIONS: The spontaneous cure rate for a 2-day period is minimal in patients
      with both a low and a high colony count, but half of the patients with low
      urinary counts will have high colony counts after this interval. The response to
      single-dose treatment is similar in patients with low and high colony counts, and
      lower than with multiday treatment.

PMID- 8297197
TI  - Delayed diagnosis of pulmonary tuberculosis in city hospitals.
AB  - BACKGROUND: Delays in the diagnosis of tuberculosis may result in increased
      patient morbidity and in further spread of the disease. We examined the clinical
      acumen of the medical staff in the diagnosis of tuberculosis and investigated the
      reasons for delay in the identification and treatment of patients with pulmonary
      tuberculosis. METHODS: A retrospective chart review was undertaken between July
      1985 and June 1988 on all patients with culture-proven pulmonary tuberculosis at
      two inner city hospitals. Time intervals between admission and the clinical
      suspicion, diagnosis, and treatment of tuberculosis were determined. Clinical
      features were evaluated for their effect on these time intervals. RESULTS: Eighty
      five patients with culture-proven pulmonary tuberculosis were identified.
      Tuberculosis was suspected in 36 patients on admission. By the end of 1 week,
      tuberculosis was confirmed in 50 patients and suspected in 23 others. Twenty
      percent of patients either died or were discharged before the diagnosis of
      tuberculosis was made. Older patients (> 65 years) were misdiagnosed more
      commonly than younger patients (82% vs 48%). Patients without respiratory
      symptoms were misdiagnosed more frequently (78% vs 49%) than were those with
      symptoms. Other reasons for delayed diagnosis and treatment included low use of
      tuberculin skin tests, misinterpretation of unusual chest roentgenograms, and
      waiting for culture results in patients with negative acid-fast smears.
      CONCLUSIONS: The diagnosis and treatment of patients with pulmonary tuberculosis
      is often delayed owing to atypical presentations and slow confirmation by
      culture. Improved clinical acumen, development of rapid diagnostic tests, and the
      institution of early empiric therapy are desirable to control this disease.

PMID- 8297198
TI  - Acute liver injury associated with nonsteroidal anti-inflammatory drugs and the
      role of risk factors.
AB  - BACKGROUND: Hospitalizations for acute liver injury in the absence of a viral
      infection or any other well-defined pathologic finding that could have caused it
      is rare. In this study, we included both outpatients and hospitalized patients
      with acute liver injury to estimate the risk of clinically important acute liver
      injury associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs)
      and to study the role of certain risk factors. METHODS: This was a retrospective
      cohort study with secondary case-control analysis. The study included 536 general
      practitioners' practices in England and Wales for the period October 1987 through
      August 1991. A total of 625,307 persons who received more than 2 million
      prescriptions for one of 12 NSAIDs were followed up to estimate the risk of newly
      diagnosed acute liver injury. RESULTS: There were 23 cases of acute liver injury.
      The incidence of acute liver injury was 3.7 per 100,000 NSAID users or 1.1 per
      100,000 NSAID prescriptions. None of the cases had a fatal outcome. Sulindac was
      the only NSAID with a substantially greater risk than that for the overall NSAID
      group. Users of NSAIDs who had rheumatoid arthritis had a 10-fold increased risk
      of acute liver injury compared with NSAID-treated patients with osteoarthritis.
      Concomitant exposure to other hepatotoxic medications also increased the risk.
      Transient minor increases in liver test values were not a useful predictor of
      diagnosed NSAID-associated acute liver injury. CONCLUSIONS: Although NSAIDs have
      been found to be associated with acute liver injury in a small number of persons,
      the risk is sufficiently small as to be of minimal concern for most NSAIDs.

PMID- 8297199
TI  - Individual responses to a cholesterol-lowering diet in 50 men with moderate
      hypercholesterolemia.
AB  - BACKGROUND: Dietary modification is the recommended first step in the treatment
      of hypercholesterolemia. However, the efficacy of the National Cholesterol
      Education Program Step 1 Diet in outpatients with hypercholesterolemia has been
      debated. METHODS: Fifty normotriglyceridemic men whose ad libitum low-density
      lipoprotein (LDL) cholesterol levels were 4.14 to 5.69 mmol/L (160 to 220 mg/dL)
      participated in a two-period outpatient diet counseling study that used a 1-month
      high-fat, high-saturated fatty acid period (Hi-Sat) and a 4-month low-fat, low
      saturated fatty acid period (Step 1 Diet). Lipid, lipoprotein levels, and plasma
      triglyceride fatty acids were measured five times during the last 2 weeks of each
      dietary period and averaged for each patient. Dietary intake was assessed by 7
      day food records. During the Hi-Sat period, an LDL turnover study was done to
      determine the fractional catabolic rate of LDL. RESULTS: The mean reduction in
      total and LDL cholesterol levels achieved by diet was 0.54 mmol/L (21 mg/dL) and
      0.39 mmol/L (15 mg/dL), respectively. These responses equaled those predicted
      from metabolic ward investigations. While dietary responsiveness was normally
      distributed, there was marked individual variation in response. The mean (+/- SD)
      for quartiles of LDL responsiveness were +0.41 +/- 0.21 mmol/L (+16 +/- 8 mg/dL),
      -0.16 +/- 0.13 mmol/L (-6 +/- 5 mg/dL), -0.57 +/- 0.16 mmol/L (-22 +/- 6 mg/dL),
      and -1.16 +/- 0.26 mmol/L (-45 +/- 10 mg/dL). These differences in response were
      partially explained by dietary adherence, baseline fractional catabolic rates of
      LDL, and the change in plasma triglyceride palmitate level. CONCLUSIONS: The Step
      1 Diet is effective in lowering LDL cholesterol levels for many
      hypercholesterolemic men, and with appropriate counseling, outpatients can
      achieve results predicted by inpatient metabolic diet studies. Nonetheless, the
      responsiveness for individuals is highly variable, and this variability is
      influenced by both compliance and biologic factors. Since many men achieved LDL
      cholesterol levels low enough to remove the need for drug therapy in primary
      prevention for coronary heart disease, dietary therapy should remain the initial
      approach to the treatment of hypercholesterolemia.

PMID- 8297200
TI  - Early identification and isolation of inpatients at high risk for tuberculosis.
AB  - BACKGROUND: Although it has been recommended that all patients suspected of
      having tuberculosis be placed in isolation, the feasibility of this
      recommendation has not been investigated. METHODS: Forty-three patients with
      pulmonary tuberculosis were compared with 43 control subjects. The control
      subjects had submitted expectorated sputum, and were culture negative. Variables
      included chest roentgenogram results, and risk factors used by the Centers for
      Disease Control and Prevention (Atlanta, Ga) to identify patients at increased
      risk for tuberculosis. RESULTS: Potential control subjects outnumbered patients
      by 92:1. Although a positive tuberculin skin test, foreign birth, and weight loss
      were more common in the patients, 86% of the control subjects had at least one
      risk factor for tuberculosis. Chest roentgenograms consistent with tuberculosis
      (cavities or apical or nodular infiltrates) were found in 86% of the patients,
      but in only 16% of the control subjects (odds ratio, 31.7; 95% confidence
      interval, 8.6 to 127.7). The positive and negative predictive values of a
      consistent chest roentgenogram were 6% and 99.8%, respectively. The sensitivity
      of testing a single sputum specimen was 81%, yet almost half of the control
      subjects had only one specimen submitted. Of the inpatient cases, 58% were not
      identified on admission with a median delay of 13 days before isolation.
      CONCLUSIONS: Isolating all the patients at the time sputum is submitted for
      testing is not practical and would have resulted in a 92-fold overuse of
      isolation rooms. The chest roentgenogram was of great value in identifying
      patients who did not require isolation and was the best available means of
      identifying inpatients at high risk for active pulmonary tuberculosis.

PMID- 8297201
TI  - Clinical manifestations of vasculitis in patients with solid tumors. A case
      report and review of the literature.
AB  - Vasculitis is characterized by inflammatory changes and necrosis of blood
      vessels. Involvement of arteries and veins of diverse sizes throughout the body
      is possible and results in a multiplicity of clinical manifestations. Primary and
      secondary forms of vasculitis exist. Secondary vasculitis has been linked to
      several processes, including infections, drugs, and allergic, rheumatologic, and
      neoplastic disease. The majority of patients with malignant neoplasm-associated
      vasculitis who have been described had hematologic neoplasms. We report a patient
      with adenocarcinoma of the colon and vasculitis and review the 36 cases of
      vasculitis in patients with solid tumors documented in the world literature. The
      most common malignant neoplasms were non-small-cell lung cancer and prostate,
      breast, colon, and renal cancer. Cutaneous leukocytoclastic vasculitis and nerve
      and muscle microvasculitis were the most frequently observed vasculitic subtypes.
      Importantly, in 71% of the cases, manifestations of vasculitis appeared before or
      concurrent with the initial recognition or the relapse of the tumor. Management
      strategies that met with success in at least half the patients in whom they were
      used included corticosteroids, cyclophosphamide, and treatment of the underlying
      cancer. Prognosis may be primarily related to the ability to control the
      malignant neoplasm, as most of the patients who died did so because of tumor
      progression.

PMID- 8297202
TI  - Ranitidine pharmacokinetics and central nervous system.

PMID- 8297203
TI  - Gangrene of the tongue.

PMID- 8297204
TI  - Do-not-resuscitate orders and the cost of death.

PMID- 8297205
TI  - Moonshine, lead poisoning, and pragmatism.

PMID- 8297206
TI  - Unilateral gynecomastia induced by treatment with diltiazem.

PMID- 8297207
TI  - The role of c-type cytochromes in catalyzing oxidative and photosynthetic
      electron transport in the dual functional plasmamembrane of facultative
      phototrophs.

PMID- 8297208
TI  - Transient, specific and extremely rapid release of osmolytes from growing cells
      of Escherichia coli K-12 exposed to hypoosmotic shock.
AB  - The influence of hypoosmotic shock on the solute content of growing Escherichia
      coli K-12 cells was investigated at 37 degrees C. Within 20 s after the shock the
      cells had released most of their osmolytes K+, glutamate and trehalose. This
      release was specific and not due to rupture of the cell membrane, since under
      these conditions i) the cells neither lost protein nor ATP, ii) [14C]-labeled
      sucrose did not enter the cytoplasm from the periplasm, and iii) except for their
      glutamate and aspartate level, which decreased, the amino acid pool of alanine,
      lysine and arginine of the cells remained approximately constant. Within a minute
      after the shock the cells started to reaccumulate parts of their previously
      released glutamate, aspartate and K+, but not trehalose and resumed growth within
      10 min after the shock. Experiments with K(+)-transport mutants showed that none
      of the genetically-identified K+ transport systems is involved in the K(+)
      release process. Reaccumulation of K+ took place via the uptake systems TrkG and
      TrkH. The possibility is discussed that the exit of solutes after hypoosmotic
      shock occurs via several stretch-activated channels, which each allow the release
      of a specific osmolyte.

PMID- 8297209
TI  - The reduction of nitrous oxide to dinitrogen by Escherichia coli.
AB  - Escherichia coli K12 reduces nitrous oxide stoichiometrically to molecular
      nitrogen with rates of 1.9 mumol/h x mg protein. The activity is induced by
      anaerobiosis and nitrate. N2-formation from N2O is inhibited by C2H2 (Ki
      approximately 0.03 mM in the medium) and nitrite (Ki = 0.3 mM) but not by azide.
      A mutant defective in FNR synthesis is unable to reduce N2O to N2. The reaction
      in the wild type could routinely be followed by gas chromatography and
      alternatively by mass spectrometry measuring the formation of 15N2 from 15N2O.
      The enzyme catalyzing N2O-reduction in E. coli could not be identified; it is
      probably neither nitrate reductase nor nitrogenase. E. coli does not grow with
      N2O as sole respiratory electron acceptor. N2O-reduction might not have a
      physiological role in E. coli, and the enzyme involved might catalyze something
      else in nature, as it has a low affinity for the substrate N2O (apparent Km
      approximately 3.0 mM). The capability for N2O-reduction to N2 is not restricted
      to E. coli but is also demonstrable in Yersinia kristensenii and Buttiauxella
      agrestis of the Enterobacteriaceae. E. coli is able to produce NO and N2O from
      nitrite by nitrate reductase, depending on the assay conditions. In such
      experiments NO2- is not reduced to N2 because of the high demand for N2O of N2O
      reduction and the inhibitory effect of NO2- on this reaction.

PMID- 8297210
TI  - Close genetic relationship between Nitrobacter hamburgensis nitrite
      oxidoreductase and Escherichia coli nitrate reductases.
AB  - The nitrite oxidoreductase (NOR) from the facultative nitrite-oxidizing bacterium
      Nitrobacter hamburgensis X14 was investigated genetically. In order to develop a
      probe for the gene norB, the N-terminal amino acid sequence of the NOR beta
      subunit (NorB) was determined. Based on that amino acid sequence, an
      oligonucleotide was derived that was used for the identification and cloning of
      gene norB. Sequence analysis of DNA fragments revealed three adjacent open
      reading frames in the order norA, norX, norB. The DNA sequences of norX and norB
      represented complete genes while the open reading frame of norA was truncated by
      the cloning site. The deduced amino acid sequence of protein NorB contained four
      cysteine clusters with striking homology to those of iron-sulfur centers of
      bacterial ferredoxins. NorB shares significant sequence similarity to the beta
      subunits (NarH, NarY) of the two dissimilatory nitrate reductases (NRA, NRZ) of
      Escherichia coli. Additionally, the derived amino acid sequence of the truncated
      open reading frame of norA showed striking resemblance to the alpha-subunits
      (NarG, NarZ) of the E. coli nitrate reductases.

PMID- 8297211
TI  - Molecular organization of the Escherichia coli gab cluster: nucleotide sequence
      of the structural genes gabD and gabP and expression of the GABA permease gene.
AB  - We have determined the nucleotide sequences of two structural genes of the
      Escherichia coli gab cluster, which encodes the enzymes of the 4-aminobutyrate
      degradation pathway: gabD, coding for succinic semialdehyde dehydrogenase (SSDH,
      EC 1.2.1.16) and gabP, coding for the 4-aminobutyrate (GABA) transport carrier
      (GABA permease). We have previously reported the nucleotide sequence of the third
      structural gene of the cluster, gabT, coding for glutamate: succinic semialdehyde
      transaminase (EC 2.6.1.19). All three gab genes are transcribed unidirectionally
      and their orientation within the cluster is 5'-gabD-gabT-gabP-3'. gabT and gabP
      are separated by an intergenic region of 234-bp, which contains three repetitive
      extragenic palindromic (REP) sequences. The gabD gene consists of 1,449
      nucleotides specifying a protein of 482 amino acids with a molecular mass of 51.7
      kDa. The protein shows significant homologies to the NAD(+)-dependent aldehyde
      dehydrogenase (EC 1.2.1.3) from Aspergillus nidulans and several mammals, and to
      the tumor associated NADP(+)-dependent aldehyde dehydrogenase (EC 1.2.1.4) from
      rat. The permease gene gabP comprises 1,401 nucleotides coding a highly
      hydrophobic protein of 466 amino acids with a molecular mass of 51.1 kDa. The
      GABA permease shows features typical for an integral membrane protein and is
      highly homologous to the aromatic acid carrier from E. coli, the proline,
      arginine and histidine permeases from Saccharomyces cerevisiae and the proline
      transport protein from A. nidulans. Uptake of GABA was increased ca. 5-fold in
      transformants of E. coli containing gabP plasmids.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8297212
TI  - Anti-SOS effects induced in Bacillus subtilis by a phi 105 mutant prophage.
AB  - The presence of the mutant prophage phi 105cts23 in Bacillus subtilis strains
      strongly affected several biological parameters including the viability of
      protoplasts and the establishment of plasmid pC194. A defective inducibility of
      the prophage after treatments that de-repress the SOS-like response were also
      observed. Although these alterations suggested a Rec-deficient phenotype,
      homologous recombination was not impaired in these lysogenic derivatives. In
      fact, chromosomal DNA transformation in these competent cells was more efficient
      than in cells carrying the wild type prophage: cell death due to prophage
      induction upon competence development was lower than expected. Alterations in the
      response to SOS-inducing agents and to osmotic stress correlated with the
      presence of this particular mutant prophage or the cloned thermosensitive
      repressor at the permissive temperature. The induction of an anti-SOS effect is
      discussed.

PMID- 8297213
TI  - Assessing the validity of an animal model of deficient sensorimotor gating in
      schizophrenic patients.
AB  - Psychiatric researchers need specific animal models to better understand the
      neurobiology of schizophrenia. Prepulse inhibition (PPI), the reduction in
      startle produced by a prepulse stimulus, is diminished in schizophrenic patients.
      Theoretically, deficient PPI in schizophrenic patients reflects a loss of
      sensorimotor gating that may lead to sensory flooding and cognitive
      fragmentation. In rats, PPI is disrupted by systemic administration of dopamine
      agonists or by manipulations of neural circuitry linking the limbic cortex,
      striatum, pallidum, and pontine reticular formation. This loss of PPI in rats may
      be a useful model for studying the neurobiology of impaired sensorimotor gating
      in schizophrenic patients. We assessed the face, predictive, and construct
      validity of this animal model. Face validity was supported: stimulus
      manipulations produced parallel changes in PPI in humans and rats, and the
      dopamine agonist apomorphine disrupted PPI in rats, mimicking PPI deficits in
      schizophrenics. Predictive validity was supported: the ability of antipsychotics
      to restore PPI in apomorphine-treated rats correlated with clinical antipsychotic
      potency (rs = .991) and D2-receptor affinity (rs = .893). Antipsychotics that
      restore PPI in apomorphine-treated rats include "typical" antipsychotics and the
      "atypical" antipsychotic clozapine. Construct validity was supported: PPI was
      disrupted in rats when dopamine was infused into the nucleus accumbens; this
      effect was blocked by haloperidol. The loss of PPI in dopamine-activated rats may
      be a valid animal model of sensorimotor gating deficits in schizophrenic
      patients. This model may help us understand the neurobiology of cognitive
      deficits in schizophrenic patients.

PMID- 8297214
TI  - Clinical response to clozapine in patients with schizophrenia.

PMID- 8297215
TI  - The relation of parenthood to suicide.

PMID- 8297216
TI  - Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine,
      autonomic, and cardiovascular effects.
AB  - BACKGROUND: To begin applying basic neuropharmacological hypotheses of
      hallucinogenic drug actions to humans, we generated dose-response data for
      intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine,
      cardiovascular, autonomic, and subjective effects in a group of experienced
      hallucinogen users. METHODS: Dimethyltryptamine, an endogenous mammalian
      hallucinogen and drug of abuse, was administered intravenously at 0.05, 0.1, 0.2,
      and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline
      placebo-controlled, randomized design. Treatments were separated by at least 1
      week. RESULTS: Peak DMT blood levels and subjective effects were seen within 2
      minutes after drug administration, and were negligible at 30 minutes.
      Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil
      diameter, and rectal temperature, in addition to elevating blood concentrations
      of beta-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood
      levels rose equally in response to all doses of DMT, and melatonin levels were
      unaffected. Threshold doses for significant effects relative to placebo were also
      hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to
      3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects
      than those with two or fewer exposures. CONCLUSIONS: Dimethyltryptamine can be
      administered safely to experienced hallucinogen users and dose-response data
      generated for several measures hypothesized under serotonergic modulatory
      control. Additional studies characterizing the specific mechanisms mediating
      DMT's biological effects may prove useful in psychopharmacological investigations
      of drug-induced and endogenous alterations in brain function.

PMID- 8297217
TI  - Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects
      and preliminary results of a new rating scale.
AB  - BACKGROUND: Validation of animal models of hallucinogenic drugs' subjective
      effects requires human data. Previous human studies used varied groups of
      subjects and assessment methods. Rating scales for hallucinogen effects
      emphasized psychodynamic principles or the drugs' dysphoric properties. We
      describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT),
      an endogenous hallucinogen and drug of abuse, in a group of experienced
      hallucinogen users. We also present preliminary data from a new rating scale for
      these effects. METHODS: Twelve highly motivated volunteers received two doses
      (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate "nonblind,"
      before entering a double-blind, saline placebo-controlled, randomized study using
      four doses of IV DMT. Subjects were carefully interviewed after resolution of
      drug effects, providing thorough and systematic descriptions of DMT's effects.
      They also were administered a new instrument, the Hallucinogen Rating Scale
      (HRS). The HRS was drafted from interviews obtained from an independent sample of
      19 experienced DMT users, and modified during early stages of the study. RESULTS:
      Psychological effects of IV DMT began almost immediately after administration,
      peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes.
      This time course paralleled DMT blood levels previously described. Hallucinogenic
      effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and
      included a rapidly moving, brightly colored visual display of images. Auditory
      effects were less common. "Loss of control," associated with a brief, but
      overwhelming "rush," led to a dissociated state, where euphoria alternated or
      coexisted with anxiety. These effects completely replaced subjects' previously
      ongoing mental experience and were more vivid and compelling than dreams or
      waking awareness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and
      somaesthetic, while 0.1 mg/kg elicited the least desirable effects. Clustering of
      HRS items, using either a clinical, mental status method or principal components
      factor analysis provided better resolution of dose effects than did the
      biological variables described previously. CONCLUSIONS: These clinical and
      preliminary quantitative data provide bases for further psychopharmacologic
      characterization of DMT's properties in humans. They also may be used to compare
      the effects of other agents affecting relevant brain receptors in volunteer and
      psychiatric populations.

PMID- 8297218
TI  - [Catheter ablation of tachycardia of the outlet right ventricle using
      radiofrequency as power source].
AB  - Two female patients, 54 and 38 years-old with refractory ventricular tachycardia
      were undertaken to electrophysiologic study for diagnosis and radiofrequency
      ablation of their arrhythmias. The tachycardias were only inducible with
      intravenous isoproterenol infusion. The site of the origin of ventricular
      tachycardia was localized in the right ventricular outflow tract in both cases.
      Radiofrequency current was delivered at 40V (40-60s) in each patient and was
      followed by complete abolition of ventricular arrhythmias.

PMID- 8297219
TI  - [Lutembacher's syndrome].
AB  - A 48-years-old woman with Lutembacher syndrome with a clinical and laboratory
      finding of atrial septal defect, of the "ostium secundum" type and without
      pulmonary hypertension was reported. We observed, from diagnostic viewpoint, that
      the electrocardiographic finding of left atrial overload and the
      echocardiographic pattern of mitral stenosis where the most important diagnostic
      sign the mitral valve involvement. The patient underwent surgery and the atrial
      septal defect was closed with a patch. After the surgery the signs of atrial
      septal defect where very poor and the signs of mitral stenosis dominated the
      clinical picture of the patient. Although we did not make any intervention at the
      mitral valve, the patient had a good outcome and until the present date she is in
      functional class I.

PMID- 8297220
TI  - [Adverse reactions to the main drugs used in cardiology].

PMID- 8297221
TI  - [Endothelial function and coronary vasospasm after heart surgery].

PMID- 8297222
TI  - [Antihypertensive effect of urapidil in mild to moderate arterial hypertension.
      Randomized, double-blind versus placebo study].
AB  - PURPOSE: To evaluate the efficacy and tolerability of urapidil (a new central and
      peripheral antihypertensive agent) in patients with mild to moderate essential
      hypertension. METHODS: Thirty-one patients were randomized, double-blindly, to
      receive either placebo (15 patients) or urapidil (16 patients) for 3 months. The
      initial dose of urapidil was 30mg twice daily, per oral. The dose was increased
      progressively till achievement of good blood pressure control or the dose of 60mg
      three times a day. RESULTS: Seventy percent of the patients on urapidil group
      responded to therapy against 30% on the placebo group. There were 3 cases of
      hypertensive crises (2 on urapidil and 1 on placebo) on the early therapy. The
      adverse events with urapidil were unfrequent and the most common were headache
      and dizziness. There were no modification on blood sugar and lipids level.
      CONCLUSION: Urapidil appears to be a safe antihypertensive agent in the treatment
      of mild to moderate essential hypertension. It also did not demonstrate any
      clinical effect on the carbohydrates and lipids profile.

PMID- 8297223
TI  - [Pravastatin: efficacy and safety in elderly patients with primary
      hypercholesterolemia. Open multicenter study].
AB  - PURPOSE: To analyze the response of hypercholesterolemic elderly patients to
      pravastatin. METHODS: Two hundred and sixty six primary hypercholesterolemics, 65
      to 80 years of age, after ingesting a standard diet for four weeks, received 10mg
      of pravastatin for 12 weeks. RESULTS: Average reductions of 24% or more were
      observed for TC and LDL-C, and more than 60% of those reductions were considered
      good or excellent (above 20%). Increases in HDL-C (6.6%) and the reduction of TG
      (21.2%) were significant. Patients 65 to 70 years old compared to patients 71 to
      80 years old did not show significant response differences, however, the 71 to 80
      year old patients had smaller reductions in TC and LDL-C but greater increases in
      HDL-C. The drug was very well tolerated, with an incidence of adverse events of
      only 10.5%, none of which resulted in the discontinuation of drug administration.
      There were significant increases in hepatic enzymes (SGOT and SGTP), however the
      variations did not have clinical significance. For CK changes were not
      significant. CONCLUSION: Primary hypercholesterolemic elderly seem to respond to
      pravastatin in a similar way as middle age patients. The effects on the lipid
      fractions are significant, adverse effects are rare and the drug is very well
      tolerated. Thus it should be considered a first line hypolipidemic drug.

PMID- 8297224
TI  - [Analysis of the composition and spatial disposition of atherosclerotic plaques
      localized in epicardial coronary artery bifurcations in adults].
AB  - PURPOSE: To analyze macro and microscopic features of atherosclerotic plaques
      located in bifurcation of coronary arteries, defining their spatial disposition
      in those sites. METHODS: We studied 38 bifurcations of coronary arteries of
      patients whose cause of death was related to coronary artery disease. Histologic
      sections of 0.5mm were sequentially made from the main artery to the secondary
      branches. They were stained with hematoxilin-eosin technique. Histological
      analysis evaluated: a) morphologic composition of the plaques, b) degree of
      obstruction and c) plaque's disposition. RESULTS: a) Plaque's composition:
      fibrolipid plaques constituted 80% of the cases and mingled focal atrophy of the
      media at the base of the plaque in 61% with spots of total destruction and
      rupture of the elastic layers in 30%; b) degree of obstruction: ranged from 20%
      to 95%, with average 60 +/- 28%; c) disposition of plaques: we verified
      morphologic variation along the plaque, most of them (71%) being eccentric at
      bifurcation and not reaching the beginning of flow divider walls. CONCLUSION:
      Atherosclerotic plaques located in bifurcation of coronary arteries of adults are
      often fibrolipid plaques, eccentric, and their spatial disposition on those sites
      spare the beginning of the inner walls, reaching the outer walls.

PMID- 8297225
TI  - ["Reverse reperfusion" in myocardial scintigraphy perfusion with technetium-99m
      isonitrile. Incidence and clinical implications].
AB  - PURPOSE: Evaluation of the incidence and clinical implications of perfusion
      defects that appear worse in the rest than the stress myocardial perfusion
      imaging with technetium-99m isonitrile (MIBI), similar to the reverse
      redistribution described with thallium-201. METHODS: The studies of 730
      consecutive patients with known or suspected coronary artery disease who
      underwent either diagnostic or prognostic (after myocardial infarction)
      technetium-99mMIBI planar scans were reviewed. Usual planar images were
      subjective and semi-quantitative analyzed. Patients were divided in two groups
      according to the indication of the test. The incidence of the reverse reperfusion
      pattern, the correlative findings with the angiographic coronary anatomy, when
      available, and its clinical implications were assessed. RESULTS: Three in the 540
      (0.55%) patients of the diagnostic group and 6 out of the 190 (3.15%) patients of
      the myocardial infarction group have shown the "reverse reperfusion" pattern,
      with an overall incidence of 1.23%. Perfusion defects were anterior in 2 and
      inferior in 1 patient of the diagnostic group, compared to 4 anterior and 2
      inferior within the prognostic population patients. One patient of the diagnostic
      group and 4 of the prognostic group showed ST-T changes on the exercise ECG. All
      of them achieved at least 85% of the maximum predicted heart rate during the
      stress test. The only patient with the "reverse reperfusion" pattern in the
      diagnostic group had no coronary disease at angiography, while the 6 patients in
      the post myocardial infarction group have shown either an occluded (2 cases) or
      recanalized infarct related artery (2 cases) and remote coronary disease (2
      cases). Three of them underwent successful coronary angioplasty based on clinical
      and laboratory evidences of ischemia. CONCLUSION: The "reverse reperfusion" with
      technetium 99-m MIBI is an uncommon finding and may be associated with
      jeopardized myocardium after infarction, although its predictive value for
      recanalized infarct related artery seems to be very low. It seems to provide no
      added value towards coronary artery disease diagnosis. Additional experience is
      required in selected subgroups of patients in order to clarify the clinical value
      of the "reverse reperfusion" pattern with the technetium-99m MIBI.

PMID- 8297226
TI  - [High-resolution electrocardiography in arrhythmogenic right ventricular
      disease].
AB  - PURPOSE: To determine the value of the high-resolution ECG for the differential
      diagnosis of arrhythmogenic right ventricular disease. METHODS: A group of 33
      patients were studied, 16 males, mean age 34 +/- 16 years. All patients presented
      non-sustained or sustained or repetitive monomorphic ventricular tachycardias,
      with left bundle branch block morphology. The anatomic and functional evaluation
      of the right ventricle was made by a previous echocardiogram. No patient
      presented left ventricular or septal pathology. High-resolution ECG were obtained
      from a Corazonix-Predictor II program. In the filtered QRS was analyzed root mean
      square of the last 40ms QRS, the final lasting of the low amplitude signals < 40
      microV and filtered QRS duration. Ten patients underwent to electrophysiological
      study with right ventricular mapping. RESULTS: The ventricular tachycardias was
      non-sustained in 18 patients, sustained in 8 and repetitive monomorphic in 7
      patients. The echocardiogram was normal in 23 patients, and all these also
      presented normal high resolution ECG. Among the 10 patients with altered
      echocardiogram, 9 presented abnormal high-resolution ECG (sensibility 90%;
      specificity 100%; positive predictive value 100%; negative predictive value 96%;
      efficacy of the method to define the presence of manifested right ventricular
      pathology was 96%). Among the 10 patients with altered echocardiogram, 8
      underwent to electrophysiological study. In all was detected an abnormal
      ventricular mapping and abnormal high-resolution ECG. CONCLUSION: The high
      resolution ECG is an useful method to define a right ventricular manifested
      pathology in presence of arrhythmogenic disease of this cavity.

PMID- 8297227
TI  - [Comparison between the use of unifoil double balloon and bifoil balloon in
      successful mitral valvuloplasty by balloon catheter].
AB  - PURPOSE: To compare immediate and long term results balloon mitral valvuloplasty
      (BMV) using double balloon or bifoil balloon. METHODS: One hundred and thirteen
      consecutive cases of BMV used aleatory double balloon (group DB--55 cases) or
      bifoil balloon (group BF--16 cases). Patients were similar regarding to age, sex,
      valvopaty etiology, functional class and echocardiographic score. Seventy one
      (63%) patients achieved 12 months follow-up. RESULTS: In group DB there were 2
      (4%) insuccess, 2 (4%) cardiac tamponade and 2 (4%) deaths, 91% patients had
      immediate criteria of success. Mitral valve area (MVA) increased from 0.8 to
      1.69cm2 and mitral gradient (G) by echodopplercardiographic (ECHO) decreased from
      17.9 to 4.8mmHg. Three (5%) patients developed severe mitral regurgitation (MR)
      and needed surgical intervention. At follow-up 2 (4%) developed mitral
      restenosis. MVA estimated by ECHO study after one year follow-up was inferior to
      1.15cm2 in 15 (32%) cases, between 1.5 and 2.0cm2 in 17 (37%) and superior to
      2.0cm2 in 14 (31%). In group BF there were 2 (12.5%) insuccess, 4 (25%) developed
      severe MR occurring 1 death immediate post-operative mitral valve replacement.
      Among 14 (87%) success cases, MVA increased from 0.8 to 1.89cm2 and G decreased
      from 18 to 6.4mmHg. Lately 2 (12.5%) needed surgical intervention because
      significative MR. At 12th month follow-up the ECHO study showed that in one (10%)
      case MVA was < 1.5cm2, and in 3 (27%) cases was between 1.5 and 2.0cm2.
      CONCLUSION: There were similar good results in both groups, however group DB had
      more restenosis, cardiac tamponade and vascular complications and group BF had
      more severe MR.

PMID- 8297228
TI  - [Artificial respiration with extracorporeal membrane oxygenator in arteriovenous
      position without pump. Experimental study].
AB  - PURPOSE: To test the hypothesis of respiratory support and to study the
      consequent hemodynamic alterations, we performed pumpless A-V ECMO using a 1.2m2
      polipropylene hollow fiber membrane oxygenator, specially adapted from
      conventional model utilized in routine cardiac surgery. METHODS: Two canine
      groups of six dogs each were studied. Group 1 had normal lungs and group 2 acute
      respiratory failure induced by 0.035ml/kg intravenous oleic acid. The dogs were
      anesthetized and maintained in apnea with curare. Heparin was given in a single
      dose of 400U/kg. Gasimetric and hemodynamic parameters were monitored each 30
      minutes during a 3 hour period. Then the oxygenator was discontinued and after 15
      minutes a final arterial blood gas sample was taken for analysis. RESULTS: Blood
      samples at 3 hours have shown a mean PaO2 of 260.6mmHg in group 1 and 114.4mmHg
      in group 2 and PaCO2 of 54.3 and 56.2mmHg, respectively. After the oxygenator was
      discontinued PaCO2 levels increased to 161.6 and 193.7mmHg, respectively. The
      hemodynamic parameters shown few alterations. CONCLUSION: In both groups pumpless
      A-V ECMO was able to maintain gasimetric parameters within acceptable patterns
      and compatible with life, with few hemodynamic alterations. However, an adequate
      mean arterial blood pressure is needed to provide flow through membrane
      oxygenator.

PMID- 8297229
TI  - [Changes in electrocardiogram in V1 by precordial electrode malposition].
AB  - PURPOSE: To evaluate changes in the electrocardiogram (ECG) with incorrect
      positioning of the chest lead for V1, placed in the second and third right
      intercostal spaces. METHODS: Two hundred and five patients were studied after a
      conventional ECG, with the record of tracings where the chest electrode for V1
      was placed at the second and third right intercostal spaces at the right sternal
      border. These tracings were then compared with the former one and changes
      observed in the P wave, QRS complex and T wave registered and submitted to
      statistical analysis. Patients age ranged from 6 to 89 years, mean 46. Whites
      comprised 79%, black 6% and mulattos 15%. Women totalized 62% and men 38% of the
      sample. Clinical diagnosis were arterial hypertension (50%), no apparent cardiac
      disease (41%), coronary atherosclerotic heart disease (4%), mitral valve prolapse
      and other organic heart disease (5%). RESULTS: Negativation or accentuation of
      negative terminal forces of P wave were present in 84% of the patients,
      alterations in the QRS complex in 75% of the cases, and in the T wave in 66% of
      the cases, with confidence intervals of 0.7898 to 0.8901; 0.6907 to 0.8092; and
      0.6163 to 0.7437, respectively. CONCLUSION: Important changes in the ECG record
      may occur with high probability if the chest electrode for lead V1 is placed
      above the standard place.

PMID- 8297230
TI  - [Neuromuscular abnormalities in disuse, ageing and cachexia].
AB  - Cachexia, ageing and disuse and their effects on the human and animals
      neuromuscular system are reviewed. Disuse induces reduction of muscle fibers
      (mainly II) diameter with peripheral myofibrils lost; there is no core-targetoid
      or even reduction on myophosphorilase activity, both typical of denervation; the
      acetylcholine spontaneous release and trophic factors on myoneural junction are
      maintained; muscle fibers could change to angular shape. Ageing affects nerve and
      muscle by a continuous and progressive process of denervation and reinnervation;
      the number of motor units diminishes in sixties without any denervation electric
      activity; there is also reduction on the amount of ACh release on terminal
      neurons and mitochondrial oxidative capacity leading to compensatory type I
      muscle fiber number increase. Cachexia also induces reduction on muscle fibers
      diameter first on legs and then on arms and trunk; there is type II atrophy with
      occasional angular fibers, RNA/proteic synthesis reduction and normal DNA.

PMID- 8297231
TI  - [Prevalence of headache as an symptom in a urban area of Salvador, Bahia].
AB  - The prevalence of headache was studied as part of an epidemiologic survey of
      neuropsychiatric disorders carried out with an adult sample (N = 1,511) of an
      urban area of Salvador City, Bahia, Brazil. The overall prevalence of headache
      complaints was 14.8%, significantly higher among the eldest, female, less
      educated, migrants, unemployed, low SES and married/divorced. Stratified analysis
      for age and gender as confounders erased out the effect of marital status and
      socio-economic status indicators. The presence of psychiatric disorders was
      strongly, significantly associated with the prevalence of headache (odds ratio of
      4.2). These results are compared to the international literature, emphasizing the
      extremely lower rates found as well as the profiles of risk factors completely
      distinct from those reported in other sociocultural realities.

PMID- 8297232
TI  - Epilepsy and anxiety.
AB  - We have analyzed 155 subjects with STAI (State-Trait Anxiety Inventory): 75
      epileptic patients and 80 normal subjects used as a control group. A higher trait
      anxiety score (chronic anxiety) than that of controls was found for the epileptic
      group. For the epileptic group higher levels of the A-trait occurred in patients
      with EEG abnormalities with left temporal localization. We have also observed
      that the shorter the epilepsy lasts (less than two years), the higher the trait
      anxiety levels. Convulsions and awareness loss during epileptic seizures do not
      modify state and trait-anxiety scores.

PMID- 8297233
TI  - [Cerebrovascular diseases as multiple cause of death in Salvador: magnitude and
      space differences of mortality omitted in official statistics].
AB  - Social inequalities and the excess (%) in mortality by cerebrovascular diseases
      (CVD) unregistered in the official death statistics were studied in Salvador,
      Brazil, 1988. In an ecological spacial (aggregate) desing, all death mentioning
      CVD as basic and as associated cause of death were reviewed and distributed,
      according to their addresses by 66 geographical zones. The mortality rates by CVD
      (basic+associated) ranged from 22.94 to 376.62/10,000 adults. The mortality
      fraction not included in the official statistics was 29.1% for Salvador with
      means between 16.12 and 33.72% in the group of zones of very low to those in the
      high mortality levels. Seven out of 16 zones included in the 4th quantil showed
      exceptionally high mortality rates (above those of Salvador + 1.64 x standard
      deviation corrected by the zones population). The authors discuss possible
      explanations for the social differences in the mortality profile.

PMID- 8297234
TI  - Intravenous methylprednisolone in HTLV-I associated myelopathy/tropical spastic
      paraparesis (HAM/TSP).
AB  - HTLV-I (Human T-lymphotropic virus type I) associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) is an immunomediated myelopathy induced by the HTLV-I. Some
      patients, specially those from Japan, seem to have a good response to steroid
      treatment. However, this has not been found in other regions of the world. High
      dose intravenous methylprednisolone has been used with success in patients with
      relapses of multiple sclerosis (MS), another autoimmune disease of the central
      nervous system. To test the effectiveness of methylprednisolone in patients with
      HAM/TSP, we devised an open trial in 23 patients. We found a very limited benefit
      of this form of treatment in these patients. Only one patient, who had the
      shortest disease duration (five months) in the whole group, showed a sustained
      benefit. We speculate that those patients with a shorter history, with presumably
      less demyelination and more inflammatory lesions, would show a better response to
      immunosuppressive treatments.

PMID- 8297235
TI  - Magnetic resonance imaging in HTLV-I associated myelopathy.
AB  - Magnetic resonance imaging of the brain and spinal cord were carried out for
      seventeen consecutive patients with HTLV-1 associated myelopathy (HAM). Eight
      patients had brain abnormalities and four had decreased thoracic spinal cord
      diameter. Brain lesions were mostly located in subcortical and periventricular
      areas. Our data suggest that diffuse central nervous system lesions are present
      in patients with HAM.

PMID- 8297236
TI  - [Neurocysticercosis in a hospital of the city of Buenos Aires: study of 11
      cases].
AB  - Eleven patients with diagnosis of possible neurocistycercosis were studied in our
      Department since 1986. All of them were adults. Eight were Bolivian citizens. The
      commonest neurological clinical manifestation were seizures and/or headache.
      Brain CT scans showed cystic lesions and calcifications in 5 patients, only
      calcifications in 3, enlarged ventricles in 2 and an isolated frontal cystic
      lesion in 1. Six out of 7 patients who were submitted to spinal fluid ELISA test
      showed positive response for cysticercosis. Patients were put on praziquantel (50
      mg/Kg/d) or albendazol (15 mg/Kg/d) with good outcome for all them. Surgery was
      carried on for treatment of enlarged ventricles (2 patients) and for a like
      expansive lesion (1 patient). The aim of this work is to underscore the fact that
      in Buenos Aires city, which previously was not within the endemic latin american
      area for cysticercosis, is now possible to find patients with the neurological
      manifestations of this parasitosis, most probably due to migration of people
      coming from the north provinces or from countries situated at its border where
      the disease is endemic.

PMID- 8297237
TI  - [Essential tremor. Clinical observations].
AB  - The authors have studied 53 patients with essential tremor, focusing its clinical
      and epidemiological aspects. There were familial history in 37.70% of all cases,
      prevailing in females (56.60%) and white people (69.80%); nevertheless this
      difference can not be assured from the statistical point of view due to lack of
      population data. We agreed that the main incidence of this syndrome occurred
      beyond the 5th decade, specially during the 6th and 7th decades. Topographically,
      we could observe that the hand tremor predominanted, with an incidence of 96.20%
      of the total number of cases, followed by head tremor (28.30%), voice tremor
      (16.99%), leg tremor (11.30%), tongue tremor (3.78%) and trunk tremor (1.88%).
      These focal tremors were seldom observed alone and we noted frequent association
      with hand tremor.

PMID- 8297238
TI  - [Neurologic semiology in a population of hearing impaired children].
AB  - A random sample of 42 sensorineural hearing impaired children (severe and
      bilateral) was studied, from special classes in Campinas, with chronological ages
      varying between 4 and 7 years old. The children of this sample were compared with
      two control groups of 42 children of the same chronological age, from regular
      classes of private and public schools. All of them were submitted to the
      traditional neurological examination. Hearing impaired children showed
      differences as to head circumference and muscle tonus. In the other examined
      items we found motor hyperactivity, cerebellar and ocular syndromes although
      there were no significant differences between the groups.

PMID- 8297239
TI  - [Evaluation of the static equilibrium in a population of hearing impaired
      children].
AB  - A random sample was organized with 42 children with congenital sensorineural
      auditory deficit (severe and bilateral) from special education schools in
      Campinas. Chronological ages ranged from 4 to 7 years of age. This sample was
      compared with two control groups of 42 children of the same chronological age but
      attending normal classes. All were submitted to 9 tests of the set of static
      equilibrium of the Evolutive Neurologic Examination. It was observed that in the
      position of equilibrium with opened eyes (test 8) there were no differences
      between the groups. In the Romberg position, the hearing impaired children of 4,
      5 and 6 years of age showed a significant decrease in the ability to do the test
      (test 9); those of 7 years of age had equal ability whether of the control or the
      deficient groups. Hearing impaired children were less able to do other static
      equilibrium tests (heel-toe or one foot or tip-toe standing tests, with opened or
      closed eyes: tests 10, 12, 16, 20, 24, 25 and 26). The use of detailed
      neurological semiology allowed us to support the alteration of the static
      equilibrium in this group of hearing impaired children.

PMID- 8297240
TI  - [West syndrome: apropos of 9 cases].
AB  - West syndrome is a peculiar form of epilepsy of infancy and childhood
      characterized by spasms or massive myoclonus, regression neuropsychomotor
      development, and EEG abnormalities referred as hipsarrhythmia. We report nine
      cases of West syndrome discussing clinical, etiological, evolutive and
      therapeutic features.

PMID- 8297241
TI  - [Actinomycosis of the central nervous system: a rare complication of
      cervicofacial actinomycosis].
AB  - Central nervous system actinomycosis is a rare but treatable chronic suppurative
      bacterial infection. The case of a young immunocompetent male with actinomycosis
      of the CNS is presented. The abscess originated from a primary cervico-facial
      infection and was located in the left parasellar region. After excision of the
      mass, that showed Actinomyces colonies, the patient was treated with intravenous
      Penicillin for 42 days followed by oral administration of the drug for 30 days.
      After surgery the patient was left with mild sequelae that had improved by the
      last follow-up, 7 months later. A new CT scan at that time revealed no residual
      disease or recurrence. The early diagnosis of cerebral actinomycosis relies
      essentially on a clinical suspicion. Hence it is imperative to be aware of the
      natural history of this infection and its various modes of presentation.

PMID- 8297242
TI  - [Myopathies associated with tubular aggregates].
AB  - The authors report the case of a 58-year-old male patient with clinical and
      electromyographic features of myasthenia. Muscle biopsy with histochemistry and
      electronic microscopy made it possible to diagnose a myopathy associated with
      tubular aggregates. Attention is called to the fact that the anatomical
      pathologic alterations which were found may be present in a heterogenous group of
      patients showing a great variety of symptoms. Thus, there is no reason to
      consider the existence of a myopathy associated with tubular aggregates, since
      the anatomical and pathologic findings are inespecific and do not characterize
      any specific disease.

PMID- 8297243
TI  - Expression of a cell death marker (Clusterin) in muscle target fibers.
AB  - We report, for the first time, the expression of immunoreactivity to clusterin in
      skeletal muscle. Clusterin, a protein probably related to the process of
      programmed cell death (apoptosis), was specifically very highly expressed in
      target fibers. All target fibers found in 50 muscle biopsy samples from a variety
      of neuromuscular disorders expressed a high concentration of clusterin in the
      middle of the targets. Clusterin was not expressed in any targetoid fibers or
      cores. Acute denervation, where targets are mostly seen, may be the beginning of
      apoptosis. Hence our findings support the concept that targets are harbingers of
      acute denervation.

PMID- 8297244
TI  - [Neonatal encephalitis caused by herpes simplex: immunohistochemical diagnosis of
      a case].
AB  - The authors report the case of a female newborn infant, who had seizures and
      vesicles at the nose and inferior lip since the fifth day of life. CSF changes
      suggested an encephalitis. Signs of neurologic and respiratory deterioration were
      followed by death. Partial cranial autopsy showed a necrohemorrhagic temporal
      encephalitis without intranuclear inclusions. Immunohistochemical examination by
      the avidin-biotin-peroxidase technique with polyclonal antibodies against Herpes
      simplex type 1 and type 2 was positive to type 2 Herpes simplex virus.

PMID- 8297245
TI  - [Microsurgery of neurovascular decompression for trigeminal neuralgia: study of
      35 cases].
AB  - The authors report the study of 35 cases of microvascular decompression for
      trigeminal neuralgia. No mortality and a very low morbidity were associated with
      this procedure. The choice of the treatment and the advantages of each method are
      discussed.

PMID- 8297246
TI  - Trophic ulcers in the carpal tunnel syndrome.
AB  - A patient with carpal tunnel syndrome (CTS) and trophic ulcers is described.
      Despite the healing of the ulcers after surgery for CTS, the severe sensory
      deficit and the electrophysiological tests have not shown any significant
      improvement. We think these findings argue against the hypothesis of the sensory
      deficit being responsible for the trophic ulcers. We favor a major role for the
      sympathetic disturbances as the main cause for those lesions.

PMID- 8297247
TI  - [Acute idiopathic sensory neuropathy: a case report].
AB  - Pure sensory neuropathies are clinically characterized by paresthesias, sensory
      ataxia and areflexia without muscle weakness. We report the case of a 21 years
      old female patient with acute onset of distal paresthesias, marked sensory ataxia
      and hyporeflexia. Motor strength was normal. Sensory nerve conduction was absent
      and motor nerve conduction slightly decreased. CSF showed 2 leucocytes/mm3 and
      1.06 g/dL protein. Collagen disorder and neoplasia were not found. Type 2 fiber
      atrophy was observed on muscle biopsy, and axonal demyelination on sural nerve
      biopsy. The patient was treated with prednisone. After 1.5 years she was
      recovered, but a minor proprioceptive deficit persisted. A revision is made on
      the etiology, pathophysiology and clinical manifestations of the disease.

PMID- 8297248
TI  - [Neurocryptococcosis caused by nonencapsulated Cryptococcus neoformans].
AB  - The case of a patient with meningoencephafalitis due to a nonencapsulated strain
      of Cryptococcus neoformans is reported; he had no risk factors for the disease or
      AIDS. Clinical examination showed a chronic meningoencephalitis first diagnosed
      as tuberculosis. In the second cerebrospinal fluid (CSF) examination after a week
      from admission yeasts appeared inside macrophage cells. CSF culture in Sabouraud
      medium disclosed nonencapsulated Cryptococcus neoformans (biochemical
      identification). Sample inoculation in mouse (intraperitoneal) evidenced a
      capsule that disappeared in several consecutive cultures. The morphology of the
      yeast was studied by electronic microscopy. After treatment with amphotericin B
      and 5-fluorocytosine the patient had a favorable evolution. The significance of
      capsular material is discussed.

PMID- 8297249
TI  - [Infantile spinal amyotrophy with atypical course: report of 2 cases].
AB  - The authors report two cases of infantile spinal muscular atrophy with atypical
      evolution diagnosed by means of EMG findings. The first one is a 10 years-old
      female child who has showed a distal predominium of the muscle weakness and
      atrophy. The second patient, a 7 year-old female child, has manifested within a
      period of 4 months a rapidly progressive tetraparesis that culminated in death
      after 10 months. The authors present the most accepted classifications of the
      illness and discuss the clinical manifestations of the two patients aiming to
      characterize the clinical forms, in accordance to the literature.

PMID- 8297250
TI  - [False aneurysm of the median meningeal artery: the importance of angiographic
      diagnosis. A case report].
AB  - The purpose of this paper is to report a case of false aneurysm of the middle
      meningeal artery. The authors emphasize the value of "common" carotid angiography
      in diagnosis and treatment of this rare lesion.

PMID- 8297251
TI  - Magnetic resonance imaging in cervical spinal cord compression.
AB  - In patients with cervical spondylotic myelopathy MRI sometimes shows increased
      signal intensity zones on the T2-weighted images. It has been suggested that
      these findings carry prognostic significance. We studied 56 subjects with
      cervical spinal cord compression. Twelve patients showed an increased signal
      intensity (21.4%) and a prevalence of narrowing of the AP-diameter (62% vs 24%).
      Furthermore, in this group, there was evidence of a longer mean duration of the
      symptoms and, in most of the patients, of more serious clinical conditions. The
      importance of these predisposing factors remains, however, to be clarified since
      they are also present in some patients without the increased signal intensity.

PMID- 8297252
TI  - [The education of neurologists for the XXI century].
AB  - The training of neurologists for the practice in the coming years requires deep
      changes in the system of medical education. It is critical for the medical
      student and the resident the acquisition of a broad knowledge of scientific
      information. But physicians must also know how to use knowledge they have
      accumulated from a variety of sources. They express their knowledge through
      abilities in the wards or in ambulatory settings in order to get an accurate
      diagnosis and the proper management of a particular condition. In addition to
      that they are expected to develop ethical attitudes toward their patients, peers
      and the greater society. They must be committed to work, to independent learning
      and to rationality. To accomplish its scholarly goals medical education has to
      emphasize the development of adequate personal attributes, skills and habits of
      mind rather than the transmission of factual information. With today's technology
      all the scientific information necessary for the practice of medicine is at the
      fingertips through computers. Memorization is therefore an absolute nonsense in
      teaching. A better education involves reducing the working load and the number of
      lecture hours providing students and residents with sufficient unscheduled time
      to seek out information independently and to assess their own learning. Problem
      solving methods of teaching providing the formulation of multiple concurrent
      hypotheses, the critical analysis and evaluation of data and the application of
      new acquired knowledge as well as previously learned concepts to the solution of
      problems should be widely employed. Faculty members are guides who assist
      students and residents to develop analytical and critical skills.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8297253
TI  - Atomic-force microscopic study of dimensional changes in human dentine during
      drying.
AB  - Six 1-mm thick sections of human dentine, three parallel to the occlusal surface
      and three perpendicular to the buccal surface, were prepared from non-carious
      third molars. The enamel was ground off, and the sections were polished with
      alumina powder to remove the smear layer. Each section was imaged by atomic-force
      microscopy with 20 nm horizontal and 0.1 nm vertical resolutions, initially while
      the samples were immersed in deionized water and then periodically during drying
      at room temperature. No dimensional changes over microscopic fields of view
      (scanned areas smaller than 50 x 50 microns) could be detected within the
      precision of the measurements (< 0.5%). Across the entire sample, however,
      vertical displacements of 10-20 microns were measured. Elasticity (Bernoulli
      beam) theory was used to calculate the engineering strain required to produce
      these displacements. The magnitude of the strain was 0.04% (SD = 0.01) in the
      buccal sections in the direction of the tubule axis and 0.09% (SD = 0.02) in the
      direction normal to the tubule axis. Also, the strain alternated between tension
      and compression across the samples. It was concluded that, as determined by using
      microscopic techniques, drying-induced strain is too small to require corrections
      for tubule size and tubule density.

PMID- 8297254
TI  - Fine structure of Merkel corpuscles in the lingual mucosa of Japanese quail,
      Coturnix coturnix japonica.
AB  - By electron microscopy, these corpuscles were found exclusively in the connective
      tissue just beneath the dorsal epithelium near the lateral margin of the tongue.
      Each consisted of 4-8 Merkel cells and flattened nerve terminals arranged
      alternately. The Merkel cell was characterized by dense-cored granules, with a
      diameter ranging from 120 to 180 nm, throughout the cytoplasm. The functional
      significance of the avian Merkel cell, i.e. a mechanoreceptor cell or a trophic
      cell with the axon, still remains enigmatic, as is the case with Merkel cells of
      other vertebrates.

PMID- 8297255
TI  - Grouping of oral streptococcal species using Fourier-transform infrared
      spectroscopy in comparison with classical microbiological identification.
AB  - The grouping and identification made by Fourier-transform infrared spectroscopy
      (FT-IR) of 40 oral streptococcal strains was compared with their known taxonomic
      positions. Grouping was obtained by cluster analysis on the spectral distances
      between the first derivative spectra of the strains. Spectra were divided into
      five spectral 'windows' and cluster analysis was either on either a combination
      of all five windows or on a selected window. The oral streptococci were divided
      into two main clusters, mutans streptococci and other streptococci. This division
      was based mainly on the spectral information contained in the window between 1300
      900 cm-1, indicative of polysaccharide and phosphate-carrying compounds. In the
      grouping based on the entire spectrum, species clusters could be observed for
      Streptococcus crista, Strep. salivarius and Strep. rattus. A few strains were
      placed in wrong clusters because of intra-strain variance. It is concluded that
      the grouping of these oral streptococcal species was good and similar to the
      classical taxonomy and that FT-IR might develop into a new identification method
      for oral streptococci.

PMID- 8297256
TI  - Alteration of nerve growth factor-receptor expression in the periodontal ligament
      of the rat during experimental tooth movement.
AB  - This pilot study deals with the initial responses of neural elements showing
      nerve growth factor-receptor (NGFR) immunoreactivity in the periodontal ligament
      of rats to orthodontic forces. The animals were killed at intervals of 1, 2, 6,
      12 h and 1, 3, 5, 7 days after the insertion of elastic bands between the
      maxillary first and second molars. Serial frozen sections, prepared from each
      animal, were processed immunohistochemically to demonstrate NGFR, after which the
      periodontal ligament of the mesial root of the maxillary second molar was
      examined microscopically. In control sections, NGFR-positive neural elements were
      predominantly distributed at the apex of the bony socket on the distal side of
      the periodontal ligament. After 1 h of tooth movement, NGFR positively-stained
      nerve fibres tended to disappear slightly in both the intermediate and coronal
      regions of the distal periodontal ligament. By the third day of tooth movement,
      the periodontal ligament nerve fibres showed more intense NGFR-immunoreactivity;
      thick, positively stained nerve fibres were recognized on the distal side in
      which active bone remodelling was occurring, and a few of these fibres were
      densely distributed around blood vessels or near Howship's lacunae. The
      distribution of NGFR-positive neural elements on the mesial side increased at 5
      days of tooth movement. Finally, at 7 days of tooth movement, staining intensity
      for NGFR appeared to decrease. These findings demonstrate that an alteration in
      the distribution and the intensity of immunoreactive staining for NGFR in the
      periodontal ligament is associated with the bone remodelling induced by
      orthodontic tooth movement.

PMID- 8297257
TI  - Dental caries and treatment characteristics in human twins reared apart.
AB  - The 'reared apart' model, eliminating the effect of common environmental factors,
      is used extensively in twins research. In this study, teeth present (TP), teeth
      present excluding third molars (TPX3), teeth restored (TR), teeth restored index
      (TRI), surfaces restored (SR), surfaces restored index (SRI) and surfaces
      restored or carious (SRCI), were compared in 46 monozygotic (MZ) twin pairs and
      22 dizygotic (DZ) twin pairs separated during infancy and raised apart. The
      dental examination included charting, panoral and bitewing radiographs, study
      models and a questionnaire. Data were analysed using intraclass correlations
      (ICC) and analysis of variance (corrected for age and sex). For all
      characteristics, the MZ pairs showed greater within-pair similarity than DZ
      pairs. For MZ pairs, the ICC values for the dental characteristics were all
      statistically significant (p < 0.005): TP, 0.45; TPX3, 0.49; TR, 0.57; TRI, 0.61;
      SR, 0.46; SRI, 0.67; SRCI, 0.58. For DZ pairs, none of the ICC values reached
      statistical significance: TP, 0.04; TPX3, 0.11; TR, 0.30; TRI, 0.31; SR, 0.20;
      SRI, 0.17; SRCI, 0.26. Despite subjects being reared in different environments,
      receiving different diets and different dental professional care, the MZ findings
      demonstrated significant genetic variance (45-67%) for the number of teeth
      present, number of teeth and surfaces restored, and caries present; the DZ data
      supported this conclusion. These findings provide new evidence for a genetic
      contribution to dental caries.

PMID- 8297258
TI  - Development defects of enamel in humans with hereditary epidermolysis bullosa.
AB  - Developmental defects of enamel are often reported as a feature of the more
      severe forms of epidermolysis bullosa (EB). The purpose of this investigation was
      to determine the prevalence and character of enamel defects in each of the major
      hereditary EB types. Clinical evaluations were made on 237 individuals
      representing all of the major EB types and 58 unaffected individuals. All EB
      cases were categorized by phenotype, mode of inheritance and skin biopsy. The
      frequency of individuals having developmental enamel defects ranged from 8.6% in
      recessive dystrophic EB to 100% in junctional EB; 27.5% of the control population
      had these defects. Generalized hypoplasia characterized by either severe pitting
      and/or thin enamel was seen in all junctional EB cases but not in any other EB
      type. There was a tendency for the severe Herlitz form of junctional EB to have
      thin enamel while non-Herlitz junctional EB cases had less severe pitting and
      generally no reduction in enamel thickness. The prevalence of individuals with
      hypoplastic enamel bands was greater in the EB population (9.7%) than controls
      (1.9%). Thus individuals with simplex and dominant dystrophic EB typically have
      enamel defects that are similar in frequency and distribution to those of
      unaffected individuals. Developmental defects of enamel are a consistent feature
      of junctional EB, although the clinical expression is highly variable.

PMID- 8297259
TI  - A biometric analysis in the rat of the horizontal component of physiological
      tooth migration and its response to altered occlusal function.
AB  - The direction and amplitude of physiological tooth migration, as well as the
      influence of occlusal force on this movement, were evaluated macroscopically in
      the rat by biometric means. The first experiment, which compared the position of
      the teeth in the anteroposterior plane of the maxilla between two groups of 20
      and 28 rats killed at age 15 and 52 weeks, respectively, confirmed the distal
      direction of this drift. In a second experiment, after suppression of the
      antagonist occlusal contacts of the maxillary left dental hemiarch in nine rats,
      the migration of this hemiarch was compared to that of the hyperfunctional
      contralateral hemiarch and to that of the molars in a control group of 20 rats. A
      statistically significant (t-test) reduction of the physiological migration in
      the absence of occlusion, was revealed.

PMID- 8297260
TI  - The incidence and distribution of branched pulpal axons in the adult ferret.
AB  - Previous laboratory studies have revealed that some axons branch to supply the
      pulps of two teeth, but the incidence of such fibres in different regions of the
      jaws has not been investigated. The present study has used electrophysiological
      techniques to determine the incidence and distribution of branched pulpal axons
      in ferret maxillary and mandibular teeth. Under anaesthesia, pairs of Ag/AgCl
      electrodes were inserted into cavities in the left mandibular (10 animals) or
      maxillary (seven animals) teeth. Using these electrodes, electrical stimuli were
      applied to each tooth in turn, and averaged responses were recorded individually
      from the other teeth. The responses revealed 14 axons that branched to supply two
      mandibular teeth and for 13 of these the teeth were adjacent. The responses had
      latencies of 1-9.8 ms (mean 3.8 ms) and amplitudes of 4-320 microV (mean 49
      microV). These axons most commonly branched to supply the second and third
      premolars, and the canine and third incisor, and the branching point was always
      within the mandibular canal. Thirty-four branched axons supplying maxillary teeth
      were found (latency, 1.4-18.8 ms, mean 5.9 ms; amplitude; 5-210 microV, mean 36
      microV); 14 of these supplied adjacent teeth and they most commonly innervated
      the canine and incisors.

PMID- 8297261
TI  - Protein synthesis in the major salivary glands of the rat and the effects of re
      feeding and acute ethanol injection.
AB  - Rates of protein synthesis in the major salivary glands of the rat were
      accurately determined in vivo using the 'flooding dose' technique and the effects
      of reflex stimulation through feeding or acute ethanol treatment were assessed.
      Rats were divided into three groups. The control group was fasted overnight, the
      re-fed group was also fasted then re-fed the following morning and the third
      group received an intraperitoneal injection of ethanol after an overnight fast.
      In control rats the sublingual gland had a higher rate of protein synthesis than
      the other glands. After a feed the rate of protein synthesis in parotid glands
      was approximately double that of controls whilst that of the submandibular glands
      had increased by 24% and the sublingual glands remained unchanged. Acute ethanol
      injection led to a reduced rate of protein synthesis in all glands. The higher
      rate of protein synthesis in sublingual glands under fasting conditions may be
      related to the spontaneous secretion of fluid and protein from this gland, which
      would require a constant replenishment of secretory protein by synthesis. Protein
      synthesis in the parotid gland, like secretion, appears to be closely linked with
      the reflex stimulation caused by mastication. The smaller increase in rate of
      protein synthesis seen in the submandibular gland after a re-feed does not appear
      to have been recorded before. It could be mediated by the increased reflex
      stimuli caused by mastication or by some circulating factor. The mechanism by
      which ethanol reduces protein synthesis in all glands is uncertain.

PMID- 8297262
TI  - Effects of low fluoride concentrations on formation of caries-like lesions in
      human enamel in a sequential-transfer bacterial system.
AB  - Human enamel surfaces were exposed to sequential batch cultures of Streptococcus
      mutans NCTC 10832 in a sucrose-rich medium containing 0-5 mg/l added fluoride
      (F). In 10-day experiments, subsurface lesion formation was partly inhibited by 1
      mg/l F and completely by 2 and 5 mg/l F, but small lesions formed in 2 mg/l F in
      21-day experiments. Analysis of the spent media, together with analogous,
      bacteria-free experiments, suggested that lesion inhibition involved two main
      effects. First, inhibition of bacterial acid production reduced the pH fall,
      resulting in reduced undersaturation with respect to hydroxyapatite and
      consequently reduced rate of demineralization. Secondly, interaction of F with
      enamel mineral resulted in a small increase in reprecipitation during periods of
      supersaturation and a much larger reduction in demineralization during periods of
      undersaturation. It is concluded that, at low F concentrations, inhibition of
      bacterial acid production is a major factor in lesion inhibition, which may
      contribute significantly to caries prevention in vivo where plaque fluid F levels
      are raised by frequent topical applications.

PMID- 8297263
TI  - The influence of histatin-5 fragments on the mineralization of hydroxyapatite.
AB  - The adsorption of histatin 5 on hydroxyapatite (HAP) was determined and compared
      to that of several fragments of histatin 5, such as residues 1-16 (N16), 7-16
      (M10), 9-24 (C16), 11-24 (C14), 13-24 (C12), 15-24 (C10). The influence of the
      adsorbed peptides on the seeded crystal growth of HAP was investigated with the
      constant composition method. The adsorption affinity of the peptides as well as
      their ability to inhibit mineralization was influenced by the length of the
      peptide chain. Histatin 5 showed the highest affinity, as determined by a
      Langmuir model, whereas the smaller C10 and C12 displayed the lowest equilibrium
      uptake. The smaller C10 and C12 peptides were, on the other hand, more effective
      as crystal growth inhibitors, indicating a more efficient coverage of surface
      active sites. Electrophoretic mobility data indicated an increase in the positive
      charge at the HAP surface in the presence of these peptides, which were efficient
      HAP crystallite dispersants.

PMID- 8297264
TI  - Effects of primary auditory cortex lesions on middle latency responses in awake
      cats.
AB  - In order to clarify the role of the primary auditory cortex (AI) on middle
      latency responses (MLRs), we recorded the auditory evoked potentials (AEPs) from
      the vertex and the right and left AI areas of the skull simultaneously before and
      after creating serial lesions of the AIs contralateral and ipsilateral to the
      stimulated ear in 7 awake cats. The auditory brainstem responses (ABRs) and MLRs
      recorded from the vertex in normal awake cats revealed the presence of peaks 1-8,
      NA and PA within the analysis time of 50 msec. After there were serial AI
      lesions, (1) all the peaks remained at nearly the same latencies, (2) the
      amplitude of the NA was decreased significantly, that of the PA was slightly
      decreased and those of peaks 6, 7 and 8 were variable, and (3) the difference
      between the effects of the first operation (contralateral AI) and the second
      operation (ipsilateral AI) was not statistically significant. These findings
      indicated that the main, prominent effect of bilateral AI lesions on MLRs in the
      awake cat is a significant decrease in the NA amplitude.

PMID- 8297265
TI  - Clinical usefulness of three-dimensional reconstruction of the temporal bone from
      CT scans in cholesteatoma cases.
AB  - The importance of computed tomography (CT) in analyzing temporal bone diseases
      has increased, and the ability to reconstruct the temporal bone structures in
      three dimensions from multiple CT films has been required. In order to facilitate
      the visualization of temporal bone structures, we tried reconstructing temporal
      bone CT images three-dimensionally using a personal computer, and evaluated the
      possibility of using three-dimensional CT images clinically. Temporal bone CT
      scan films from five cases of cholesteatoma and a case of otosclerosis as control
      were examined. Four temporal bone structures (temporal bone contour, middle ear,
      mastoid, and inner ear) and cholesteatoma, extracted from enlarged black and
      white CT films, were inputted to the personal computer. Data import and image
      reconstruction procedures were performed using commercially available software.
      Our results indicate that three-dimensional reconstructions contribute to
      visualizing temporal bone structures spatially, and to choosing surgical
      approaches in difficult cases, such as petrous bone cholesteatoma. In conclusion,
      three-dimensional reconstructions using a personal computer is useful in the
      diagnosis and treatment of cholesteatoma.

PMID- 8297266
TI  - A study of the changes in the level of serum IgG4 antibody and soluble CD23 (s
      CD23) in nasal allergy patients with immunotherapy.
AB  - Specific IgG4 antibodies were determined by enzyme-linked immunosorbent assay
      (ELISA), radio allergosorbent test (RAST), and s-CD23 in a total of 17 patients
      with nasal allergy who were given immunotherapy with house dust. The following
      results were obtained. 1) From the results between the serum antigen-specific
      IgG4 and the clinical effect of immunotherapy, there are many cases showing the
      elevation of antigen-specific IgG4 antibody titer. But in the elevated cases,
      there were only 7 cases showing good and excellent responses in a clinical effect
      of 41.1%. 2) IgG4 antibody was gradually elevated in many cases during
      immunotherapy, but in a few cases, abruptly increased after the maximum tolerated
      dose was established. 3) Regarding the outcome between IgG4 antibody and IgE
      antibody, cases of rising IgG4 and decreasing IgE occurred at a rate of 41%. 4) s
      CD23 in sera gradually decreased in many cases during immunotherapy, but in a few
      cases, did not change.

PMID- 8297267
TI  - The distribution of eosinophil cationic protein positive eosinophils in the nasal
      mucosa of the nasal allergy patients.
AB  - The relationship between the distribution of eosinophils and epithelial damage of
      the nasal mucosa in nasal allergy was investigated by means of hematoxylin and
      eosin staining and a technique of immunohistochemistry using the anti-human EG2
      mouse monoclonal antibody that reacts with the secreted form of eosinophil
      cationic protein (ECP). Nasal mucosa tissue of 26 adult nasal allergy patients
      and of 24 adult non-allergic rhinitis patients was removed surgically.
      Eosinophilia in the nasal mucosa of the allergy group was greater than that in
      the non-allergy group. A great number of ECP positive eosinophils accumulating in
      the nasal mucosa of the allergy group were mostly degranulated at the superficial
      layer of the lamina propria. Desquamation of the epithelium was observed mainly
      in the area of eosinophilia with degranulation of the secreted form of ECP in the
      nasal allergy group.

PMID- 8297268
TI  - Nasal tissue eosinophils in allergic rhinitis.
AB  - The density characteristics and functional heterogeneity of nasal tissue
      eosinophils were studied. The density distribution profiles of eosinophils from
      patients with allergic rhinitis (AR) showed peaks at densities of 1.068 to 1.084
      g/ml, significantly lower than the densities of eosinophils in non-allergic
      patients with nasal polyps and chronic sinusitis (p < 0.01). The proportion of
      hypodense eosinophils in patients with AR was 43%; this was significantly greater
      than that in non-allergic subjects (p < 0.001). Patients with AR tended to have
      more EG2-positive tissue eosinophils. Furthermore, normodense eosinophils in
      nasal tissue tended to show a higher percentage of EG2-positive cells than
      hypodense eosinophils. On the other hand, circulating hypodense eosinophils
      showed a higher percentage of EG2-positive cells than normal density eosinophils.
      These results suggest that tissue eosinophils may be activated, and that the
      functional heterogeneity of eosinophils is dependent on factors other than cell
      density.

PMID- 8297269
TI  - Dental implantation to free scapular bone flap used for mandibular
      reconstruction.
AB  - Three patients who underwent mandibular reconstruction with a free vascularized
      scapular osteocutaneous flap after tumor resection are presented. Dental
      reconstruction was performed on three patients by implanting an artificial dental
      root into the grafted bone. The procedures for dental implantation were done just
      as on a normal jaw, and did not require hospitalization of the patients. They
      were followed up for 3 to 5 years after dental reconstruction. They have been
      able to masticate and ingest in a virtually normal manner during these periods.
      They also showed good appearance of the reconstructed mandible and dentes. On the
      basis of these results, the indication and evaluation of this procedure are
      discussed.

PMID- 8297270
TI  - Laryngomicrosurgery with carbon dioxide laser for laryngeal papillomatosis:
      application of a two-stage operation.
AB  - Among the many treatments reported, CO2 laser surgery has recently been applied
      in the field of laryngomicrosurgery to treat laryngeal papilloma. It is
      exceedingly difficult to cure this disease, however, because of its rapid
      recurrence following surgery. Incomplete removal of papilloma is believed to be
      caused by the difficulty of precisely identifying residual papillomas during
      surgery. In an effort to resolve this problem, we have developed a new surgical
      method which we call the "two-stage operation," in which a series of two
      operations are performed about 10 days apart. By the time of the second
      operation, the bleeding, coagulated blood, and carbonized tissue from the first
      operation have resolved, and the laryngeal image is much clearer. If additional
      lesions are found, they are removed at the second operation. We applied this
      method to several patients with recurrent laryngeal papillomatosis and obtained
      good results. This new method is clearly useful in the treatment of laryngeal
      papillomatosis, and it promises to decrease the recurrence rate. In this paper we
      present the case of a 26-year-old male with laryngeal papilloma who underwent
      surgery 1 month previously at another hospital. Laryngeal endoscopy revealed
      multiple papillomas especially of the glottis. The first operation with the CO2
      laser was performed on April 16, 1990. Visible lesions appeared to have been
      completely removed. The second operation was carried out 10 days after the first
      operation, and the small residual lesions were removed with the CO2 laser. The
      patient has been disease-free for 18 months.

PMID- 8297271
TI  - Thyroplasty type I with ceramic shim.
AB  - To improve hoarseness or misswallowing caused by unilateral recurrent laryngeal
      nerve paralysis, medialization of paralyzed vocal cord has frequently been
      performed. This method includes such techniques as injection method, insertion
      method, and arytenoid adduction, each presenting its merits and demerits. The
      insertion method which can be done while monitoring the patient's voice seems
      advantageous in that the technique is easy to perform and generally guarantees
      the voice improvement. Among insertion methods, Isshiki thyroplasty type I is the
      one most representative as well as popularized. However, since a silicone shim is
      inserted in this operation, it may be accompanied by the risks of
      carcinogenicity, foreign body reaction, and induction of collagen disease of
      silicone. Therefore we planned to use a ceramic as a safe substitute instead of
      silicone. There has been no article reporting the use of ceramic in this type of
      surgery. We used a fibrin glue to fix the ceramic shim and for hemostasis, which
      was found very useful. Hitherto, 2 cases of unilateral recurrent laryngeal nerve
      paralysis underwent Isshiki thyroplasty type I using ceramic shim with
      satisfactory results.

PMID- 8297272
TI  - Unrelated volunteer donor bone marrow transplantation: the current state of the
      art.

PMID- 8297273
TI  - Unrelated volunteer bone marrow transplantation: initial experience at St
      Vincent's Hospital, Sydney.
AB  - BACKGROUND: Only 30% of patients with leukaemia have an HLA-compatible family
      member able to act as a marrow donor. The recent development of volunteer bone
      marrow donor registries has supplied HLA-matched donors for a number of such
      individuals. AIMS: To define the problem and outcome of the first cohort of
      patients given HLA-matched unrelated volunteer bone marrow transplants at St
      Vincent's Hospital, Sydney. METHODS: Post transplant outcome of patients with
      advanced leukaemia given HLA-identical unrelated donor marrow transplants was
      compared to that of patients transplanted concurrently from HLA-identical sibling
      donors, in terms of survival, leukaemia-free survival, incidence and severity of
      acute graft-versus-host disease (GVHD), duration of neutropenia, incidence of
      infection and duration of transplant hospitalisation. RESULTS: Sixteen patients
      with advanced leukaemia and without a histocompatible family member donor
      received unrelated donor bone marrow transplants. Actuarial survival at two years
      post transplant was 30%. Actuarial survival of 23 recipients of HLA-identical
      sibling bone marrow transplants with advanced leukaemia transplanted during the
      same time period was 17% (not significant). Actuarial disease free survival at
      two years was 30% and 13% respectively. Three of five long term survivors of the
      unrelated transplants had chronic myeloid leukaemia in blastic transformation at
      the time of transplant; thus blastic transformation should not preclude
      consideration of unrelated marrow transplantation. Recipients of unrelated
      allografts had a higher incidence of acute GVHD which occurred earlier and with
      greater severity than in recipients of sibling allografts, a longer duration of
      post transplant neutropenia (24 days to reach 0.5 x 10(9)/L versus 19.5, p =
      0.07), a higher frequency of infection in the first 100 days post transplant (p =
      0.0004) and a longer duration of transplant hospitalisation (p = 0.04).
      Transplant-related complications were the commonest cause of death in the
      unrelated donor recipients, while leukaemic recurrence was the commonest single
      cause of death in the HLA-identical sibling recipients. Improvements are needed
      in prophylaxis of infection and in prevention and treatment of acute GVHD in
      recipients of unrelated donor transplants. Nevertheless, this modality provides
      curative treatment for patients with otherwise incurable haematological
      malignancies and should no longer be considered experimental.

PMID- 8297274
TI  - Historical assessment of risk factors in screening for osteopenia in a normal
      Caucasian population.
AB  - BACKGROUND: Bone mineral density (BMD) can predict fracture, however, the common
      use of historical risk factors to predict low BMD is unproven. AIMS: To identify
      significant historical risk factors for osteopenia. To establish predicting
      equations for BMD and test their ability to identify those who should be referred
      for BMD scanning. METHODS: Three hundred and twenty female and 131 male
      volunteers underwent questionnaire assessment of risk factors and BMD by dual
      photon absorptiometer at hip and spine. Significant risk factors (P < 0.05) were
      used to construct a linear regression model to predict BMD. This was cross
      validated on a second sample of 107 females and 131 males selected from the
      electoral roll analysing the ability to detect those subjects with BMD in the
      lower third of the age matched normal range. RESULTS: In women lower BMD at the
      spine was associated with increased age, decreased weight, smoking, and delayed
      menarche. Lower femoral BMD was associated with increased age, decreased weight,
      family history, inactivity, and smoking. In men lower BMD at the lumbar spine was
      associated with lower weight, and inactivity. Lower BMD at the femur was
      associated with increased age, decreased weight, family history, and low calcium
      intake. When cross validated on the second sample, the models produced
      sensitivity of 86-89% and sensitivity of 25-46%. Referring those with these risk
      factors could save 10-23% on scanning. Measuring BMD at the site in question
      remains the only accurate way of assessing an individual's risk of osteopenia.

PMID- 8297275
TI  - Evaluation of mitral valve repair by intraoperative transoesophageal
      echocardiography.
AB  - BACKGROUND: Mitral valve repair is the procedure of choice in the surgical
      management of mitral regurgitation. Intraoperative confirmation of successful
      repair is essential to the effectiveness of this procedure. AIMS: The aims of
      this study were: (a) to compare intraoperative transoesophageal echocardiography
      (TOE) with the surgeon's assessment of valve competence; (b) to assess the impact
      of routine intraoperative imaging on the hospital echocardiography laboratory.
      METHODS: Eighty-six consecutive patients undergoing mitral valve repair formed
      the study population. Valve competence following repair was assessed
      intraoperatively by: TOE; saline insufflation of the flaccid left ventricle; and
      evaluation of the pulmonary capillary wedge pressure for the presence of a
      significant V wave. RESULTS: TOE demonstrated successful valve repair (< or = 1 +
      residual regurgitation) in 75 patients (87%) and detected significant residual
      regurgitation (> or = 3+) in seven (8.2%). The mechanism of regurgitation was
      also clearly shown. Of these seven patients, four underwent immediate valve
      replacement, two had successful revision of the initial repair and one required
      valve replacement one week later. In all seven patients the valve repair had been
      assessed as successful by saline testing and only one had a post-repair V wave 10
      mmHg above the mean pulmonary capillary wedge pressure. In 30 non-selected
      patients the imaging equipment was required in theatre for 43 +/- 18 minutes.
      CONCLUSIONS: TOE is currently the most sensitive method for detection and
      quantitation of residual mitral regurgitation following valve repair. Evaluation
      can be performed within a similar time to that required for one complete
      transthoracic study and can usually be performed with minimal disruption to the
      hospital echocardiography laboratory.

PMID- 8297276
TI  - Sequential changes in the bone marrow trephine biopsy in B-cell chronic
      lymphocytic leukaemia.
AB  - BACKGROUND: Trephine biopsy of the bone marrow is integral to both diagnosis and
      prognosis in B-cell lymphocytic leukaemia (B-CLL), but its usefulness would be
      enhanced by more information on the type, degree and rate of change that occur
      over time in histologic pattern and lymphocytic infiltration. AIMS: To
      investigate these changes by serial trephine biopsy in totally untreated
      patients, in treatment-free intervals in treated patients and during intervals of
      treatment. METHODS: In 82 patients with predominantly early B-CLL observed for a
      median of 65 months (13-331), 309 trephine biopsies were carried out, a median of
      three (two to eight) per patient. The biopsies were classified into nodular,
      interstitial, mixed and diffuse patterns. Lymphocytic infiltration was
      subjectively graded into minimal (< 20%), intermediate (20-50%) and majority (>
      50%) categories and all changes were compared. RESULTS: Intensity of infiltration
      increased through this histologic range, as did the relative risk of death.
      Survival of patients with > 50% involvement was significantly poorer than those
      with < 50%. Changes in both lymphocyte numbers and pattern occurred slowly in
      early disease but quickened as the leukaemia advanced. Under treatment,
      lymphocytes decreased but the histology did not alter significantly. Examining
      the marrow for disease progression should be part of regular follow-up. It may
      help identify the minority of patients with early disease which will run a more
      active course and in whom early therapy may yet be indicated. We recommend biopsy
      at two-yearly intervals in early disease, more frequently as the leukaemia
      advances. The minimal, intermediate and majority classification in addition to
      the histologic pattern is a useful grading.

PMID- 8297277
TI  - Transoesophageal echocardiography in the investigation of stroke: experience in
      135 patients with cerebral ischaemic events.
AB  - BACKGROUND: The importance of cardiogenic embolism as a cause of cerebral
      ischaemic events may be underestimated if potential cardiac sources of embolism
      remain undetected. Transoesophageal echocardiography (TOE) is more sensitive in
      detecting such abnormalities than earlier methods and may result in more frequent
      recognition of cardiogenic embolism. AIMS: To establish in an unselected stroke
      population the prevalence of potential cardiac sources of embolism detectable on
      TOE and their relationship to atrial fibrillation and carotid stenosis. METHODS:
      One hundred and thirty-five consecutive patients with cerebral ischaemic events
      were studied using transthoracic and monoplane transoesophageal contrast
      echocardiography and carotid Duplex imaging or cerebral angiography. RESULTS:
      Thirty patients (22%) had atrial fibrillation. In 43 patients (32%), no cardiac
      source of embolism was identified; in eight echocardiography was normal. At least
      one potential cardiac source of embolism was identified in 92 patients (68%) with
      multiple findings in 41; these patients were older (70 +/- 9 years vs 61 +/- 14
      years; p = 0.0001), more frequently in atrial fibrillation (28/92 vs 2/43; p =
      0.0017) and more frequently had cortical or large subcortical stroke (71/92 vs
      23/43; p = 0.005). Carotid stenoses were detected in 55% of patients, not
      significantly different in those with and without cardiac abnormalities.
      CONCLUSION: When bias in selection of patients is avoided, TOE detects a
      potential cardiac source of embolism in most patients with cerebral ischaemia,
      particularly those older and in atrial fibrillation. Multiple cardiac
      abnormalities and coexistent carotid disease are common. The implication of these
      findings for prevention of stroke awaits age-matched controlled studies.

PMID- 8297278
TI  - Immunoreactive calmodulin in cystic fibrosis kidneys.
AB  - BACKGROUND: Microscopic nephrocalcinosis has been detected at autopsy in 35 of 38
      (92%) cystic fibrosis (CF) patients. A primary defect of calcium metabolism in
      the kidney has been postulated. Intracellular calcium and calmodulin (a calcium
      binding protein) have been shown to be increased in CF tissues. AIMS: To
      determine whether CF kidneys obtained at autopsy contain normal amounts of
      calmodulin and whether the presence of immunoreactive calmodulin correlates with
      nephrocalcinosis. METHODS: An immunoperoxidase method was used to stain kidneys
      obtained from six CF individuals aged three to 27.5 years (mean 15.75 +/- 10.2
      years) and five individuals who died of chronic debilitating disease aged eight
      to 17 years (mean 13.6 +/- 3.9 years). Calcium staining was undertaken using the
      von Kossa (silver precipitation) and Alizarin red methods. RESULTS: No
      quantifiable difference in immunoreactive calmodulin staining was demonstrated in
      autopsy renal specimens between six CF patients and five chronically diseased
      controls. Three of six CF patients aged 22.8 +/- four years and two of five
      chronically diseased controls aged eight to 16 years respectively had detectable
      immunoreactive calmodulin staining. Within the CF group the presence of
      microscopic nephrocalcinosis did not correlate with immunoreactive calmodulin
      staining. CONCLUSION: This study does not support the premise that a calmodulin
      dependent defect of intracellular calcium handling contributes to the microscopic
      nephrocalcinosis seen in CF.

PMID- 8297279
TI  - Coronary artery surgery in the elderly: long-term follow-up.
AB  - BACKGROUND: There has been controversy concerning the indications for coronary
      artery surgery in the elderly, particularly in countries where health resources
      are restricted. AIMS: To assess the results of coronary artery bypass grafting
      (CABG) in a large group of elderly subjects with regard to initial risks and long
      term follow-up. METHODS: Ninety-six consecutive patients aged 70 years or older
      underwent isolated CABG between January 1981 and December 1985. Long term follow
      up was obtained in 94 (98%). RESULTS: The mean age was 71.6 years (70-78) and
      mean duration of follow-up 73 months. Seventy (73%) were male. In 80 cases the
      myocardial score was > 10. In 22 of 90 who had left ventricular angiography the
      ejection fraction was < 50%. Hospital survival was 96% and the five year survival
      77%. It was not influenced by gender, myocardial score, ejection fraction or age
      at the time of operation. The status of survivors was reviewed in 1991. Of the 55
      long term survivors 35 (64%) were free of angina. Eight (15%) and ten (18%) were
      in the Canadian Cardiovascular Society Angina classes 1 and 2 respectively.
      Seventeen patients (31%) had symptoms of heart failure with 14 (25%) in NYHA
      class 2 and 3 (5%) in class 3. Eight patients (15%) had survived a
      cerebrovascular event during follow-up. There were 35 late deaths (37%). Sixteen
      of these were cardiac, 18 due to other causes and one unknown.

PMID- 8297280
TI  - A comparison between estimates of GFR using [99mTc]DTPA clearance and the
      approximation of Cockcroft and Gault.
AB  - BACKGROUND: The formula of Cockcroft and Gault, relating age, weight, sex and
      plasma creatinine is widely used to estimate glomerular function. Its ability to
      predict [99mTc]DTPA clearance, an accepted measure of GFR, is therefore of
      interest. AIM: To test prospectively the reliability of the formula in predicting
      the [99mTc]DTPA clearance in subjects with normal and sub-normal renal function.
      METHODS: The 24 hour creatinine clearance (Ccr), the derived clearance using the
      formula (Cder), and the [99mTc]TPA clearance have been compared in 47 male and 47
      female subjects, aged between 15 and 71 years. Obese and non-obese subjects
      (males > 90 kg, females > 80 kg body weight) were considered separately. RESULTS:
      Across the range of [99mTc]DTPA clearance studied (14 to 125 mL/minute), in non
      obese subjects, both Ccr and Cder were correlated similarly with [99mTc]DTPA
      clearance in males and females. In obese subjects as a group, Cder was also
      closely correlated with [99mTc]DTPA clearance but the scatter of data was wider.
      Among non-obese subjects, correlations were high between either Ccr or Cder and
      [99mTc]DTPA clearance values < 101 mL/minute but were not significant at
      [99mTc]DTPA clearance values > 100 mL/minute. For [99mTc]DTPA clearance values
      between 14 and 100 mL/minute, Cder was a more direct and more precise predictor
      of [99mTc]DTPA clearance [DTPA clearance = 1.01 (Cder) + 2.34, with 95%
      confidence limits of +/- 18 mL/minute] than of Ccr [Ccr = 1.34(CderC)-10.86,
      confidence limits +/- 28 mL/minute]. CONCLUSION: For very mild through to
      moderate renal failure, the formula of Cockcroft and Gault can evidently be used
      as a reasonable estimate of GFR.

PMID- 8297281
TI  - Adult congenital heart disease: principles and management guidelines--Part I.

PMID- 8297282
TI  - Cell adhesion molecules and their role in haemopoiesis and in haematological
      diseases.

PMID- 8297283
TI  - The Arthur Mills Oration--Shakespeare in daily life.

PMID- 8297284
TI  - Zollinger-Ellison syndrome caused by a mucinous cystadenocarcinoma of the ovary.

PMID- 8297285
TI  - Pulmonary angiography in pulmonary embolism.

PMID- 8297286
TI  - Corticosteroid responsive mitochondrial encephalomyopathy.

PMID- 8297287
TI  - Doxepin-induced recurrent acute hepatitis.

PMID- 8297288
TI  - Factitious acquired immunodeficiency syndrome (AIDS)

PMID- 8297289
TI  - Pure white cell aplasia.

PMID- 8297290
TI  - Acute hepatitis induced by ingestion of the herbal medication chaparral.

PMID- 8297292
TI  - The use of acronyms in medical articles.

PMID- 8297291
TI  - Migraine following the use of a 5-hydroxytryptamine antagonist.

PMID- 8297293
TI  - Patient characteristics and pathology in colorectal adenomas removed by
      colonoscopic polypectomy.
AB  - Between September 1981 and August 1987 420 patients with 565 adenomas underwent
      colonoscopic polypectomy to produce a 'clean colon'. Data from these patients
      were analysed to identify associations between patient characteristics (age and
      sex), polyp characteristics (site, size, shape, multiplicity and villous content)
      and the degree of dysplasia in the index adenoma. In univariate analysis, severe
      dysplasia in the index adenoma was significantly but weakly associated with size
      (> or = 10 mm), peduncular shape and villous architecture. Logistic regression
      confirmed an independent effect only from villous architecture. These findings
      suggest that it is unlikely that strong predictors of a patient developing a
      metachronous adenoma or colorectal cancer can be identified on the basis of an
      index adenoma found at initial colonoscopy. These patients will continue to be
      followed to investigate this question.

PMID- 8297294
TI  - The anorectal angle is not a reliable parameter on defaecating proctography.
AB  - Proctography is a standard method of investigating anorectal disorders. The
      parameters derived from this X-ray include the anorectal angle. The
      reproducibility of this measurement was assessed in 43 defaecating proctograms
      viewed by four observers on two separate occasions. Measurements were made at
      rest and during defaecation straining. Significant intra- and inter-observer
      variation was found. The anorectal angle is an inaccurate measurement, and should
      be interpreted with caution.

PMID- 8297295
TI  - Are secondary bile acids in choledochal cysts important as a risk factor in
      biliary tract carcinoma?
AB  - Since secondary bile acids have mutagenic potency and choledochal cyst patients
      with or without cyst-enterostomy have a high risk of developing bile duct
      carcinoma, we examined the hypothesis that secondary bile acids are elevated in
      the choledochal cyst and possibly cause biliary tract carcinoma. Eleven
      choledochal cyst patients with or without previous cyst-enterostomy or biliary
      tract carcinoma, seven patients with biliary tract carcinoma not associated with
      choledochal cyst and five patients with cholecystolithiasis were examined.
      Samples were directly needle aspirated from the cyst or by cannulating a tube
      into the common bile duct through the cystic duct. The concentrations of each
      bile acid in these samples were quantified by gas-liquid chromatography and
      compared. Neither the relative composition nor the absolute concentration of
      secondary bile acids (deoxycholic acid, lithocholic acid) elevated in patients
      with choledochal cyst compared with the values in the non-choledochal cyst
      patients with or without biliary tract carcinoma. The presence of biliary tract
      carcinoma or previous cyst-enterostomy did not affect the concentrations of
      secondary bile acids. The results suggest that the factor other than secondary
      bile acids can be primarily responsible for the high risk of bile duct carcinoma
      in patients with choledochal cyst.

PMID- 8297296
TI  - Laparoscopic common bile duct exploration.
AB  - Twenty-one patients underwent laparoscopic common bile duct exploration during a
      9 month period. Ten had stones flushed after ampullary dilatation. Seven had
      stones removed with a Dormier basket and one had direct common duct incision with
      T-tube insertion. Three failed attempted stone flushing and had stones removed by
      endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy.
      Operating time ranged from 1.5 to 3.5 h. Nineteen patients were discharged by the
      second postoperative day. This early experience with laparoscopic stone removal
      is encouraging, reducing the need for pre-operative or postoperative ERCP.

PMID- 8297297
TI  - Septic arthritis of the hip in infancy.
AB  - A retrospective study was undertaken of 24 infants with septic arthritis of one
      or both hips who presented to the Children's Hospital, Camperdown, during the 15
      year period from 1973 to 1989. Staphylococcus aureus was found to be the most
      common pathogen. Umbilical catheterization was a significant aetiological factor
      in seven of 10 neonates studied. Young premature infants had the poorest outcome
      in regard to permanent bony changes in the upper femur, hip instability and leg
      length discrepancy. In patients with unstable and severely damaged upper femora,
      late salvage procedures were found to be unsatisfactory.

PMID- 8297298
TI  - Bennett's fracture: a medium to long-term review.
AB  - Seventy-six patients who had sustained Bennett's fractures before 1985 comprised
      the patient base. Of these, 21 could be contacted and were reviewed at an average
      of 7 years 7 months after fracture to determine the effect of the quality of
      reduction on clinical and radiological outcome. Those cases that healed with up
      to 1 mm of fracture displacement were found to have superior results to cases
      where the reduction was less accurate. However even in those cases where a good
      reduction was not achieved the results were generally satisfactory with only one
      of 76 patients being known to have required a subsequent fusion of the first
      carpo-metacarpal joint. The subjective results in most patients had not
      deteriorated with time. It is recommended that a reduction with less than 1 mm
      displacement of the fracture be achieved in cases of Bennett's fracture. The
      particular technique by which the reduction is achieved and held is immaterial.

PMID- 8297299
TI  - Bone banking: from Tamworth Base Hospital to Royal Newcastle Hospital.
AB  - During the first 6 months of 1992, orthopaedic surgeons at Tamworth Base Hospital
      were involved in a feasibility study using allograft bone and donating femoral
      heads to Royal Newcastle Hospital Bone Bank. The two hospitals being separated by
      300 km meant that storage, packaging and transportation had to be refined in
      order to ensure sterility and safe delivery of the bone. This study was
      undertaken because of the growing need for allograft bone in revision hip
      arthroplasty at Tamworth Base Hospital. This need for allograft bone has been
      expressed by other country based orthopaedic surgeons and will only increase
      during the next few years as primary hip prostheses age and revision hip surgery
      continues to advance.

PMID- 8297300
TI  - The adverse effect of fibrin-clot inhibiting drugs on intravesical bacillus
      Calmette-Guerin efficacy for superficial bladder cancer.
AB  - Bacillus Calmette-Guerin (BCG) is currently thought to act as a biological immune
      modifier in effecting antitumour activity. Recent evidence suggests that BCG
      binding to fibronectin (FN), a tissue glycoprotein, may be a prerequisite step in
      initiating this response. Drugs inhibiting the availability of exposed FN in the
      bladder after urothelial disruption may adversely affect the efficacy of BCG.
      Data are presented of 45 patients with tumour limited to mucosa (pTa) or
      carcinoma in situ (CIS) given intravesical BCG therapy, with (group 1) or without
      (group 2) fibrin clot-inhibiting drugs concurrently during treatment. The success
      rate of 11.1% for group 1 (1/9) patients was significantly less than that of
      69.4% for group 2 (25/36), (chi 2 = 7.79, P < 0.01 Fisher's exact test)
      supporting the suggestion that the concurrent administration of fibrin-clot
      inhibiting drugs may adversely affect the outcome of BCG therapy.

PMID- 8297301
TI  - The use of taped skin closure in orthopaedic wounds.
AB  - The cosmetic result, cost effectiveness, and complication rate of three different
      types of skin closure: staples, tapes, and interrupted nylon were compared. In 68
      wounds, skin closure was randomized to staples, tapes, or interrupted 3/0 nylon
      sutures. All wounds were closed subcutaneously with interrupted undyed 2/0 dexon.
      For 3 months, 59 wounds were followed and assessed by an independent observer at
      1 and 3 months postoperatively in the outpatient department. In three different
      skin closures, the cosmetic result was superior for tapes because the wound line
      itself was finer and there were no dot scars. Tapes were the most cost-effective
      because they are the cheapest although they were not as quick to apply as
      staples. There was no difference in complication rate. Tapes also afforded the
      greatest patient comfort.

PMID- 8297302
TI  - Lilian Violet Cooper, MD, FRACS, Foundation Fellow, Royal Australasian College of
      Surgeons.

PMID- 8297303
TI  - Prenatal diagnosis of posterior urethral valves in siblings.
AB  - Posterior urethral valves are an important cause of obstructive uropathy in the
      newborn. The diagnosis may be suspected on prenatal ultrasonography, the
      consistent finding being bilateral ureterohydronephrosis together with a thick
      walled, persistently full bladder in a male fetus. There may also be variable
      degrees of oligohydramnios. This paper reports the case of siblings in whom
      posterior urethral valves were recognized prenatally. The first child progressed
      well after appropriate surgical management, but the second died within 24 h of
      birth.

PMID- 8297304
TI  - Laparoscopically assisted anterior resection for villous adenoma of the rectum.
AB  - A 57 year old female presented with symptoms from a large, sessile tubulovillous
      adenoma of the lower third of the rectum. Transanal excision was impracticable
      due to its size and anterior resection was necessary. The upper third of the
      rectum was mobilized percutaneously, using the laparoscope. The lower two-thirds
      of the rectum were mobilized transanally and a non-everted pull-through excision
      of the lower third was performed, with a hand sewn colo-anal anastomosis. A
      temporary loop ileostomy was established through a 2.5 cm abdominal incision.
      Postoperative recovery was uncomplicated. The operative technique, which may have
      other applications, is described in detail.

PMID- 8297305
TI  - An unusual cause of rectovaginal fistula.
AB  - An unusual case of rectovaginal fistula is reported. An 81 year old woman
      presented to the geriatric team with a request to review her faecal incontinence.
      It was discovered that she had a predilection for placing foreign objects in her
      vagina. In this instance a carbonated drink top had formed a rectovaginal
      fistula.

PMID- 8297306
TI  - Intraperitoneal gallstone-related sinus formation following laparoscopic
      cholecystectomy.

PMID- 8297307
TI  - Unilateral piriformis syndrome in a patient with previous melanoma.
AB  - Several years after undergoing surgery for a malignant melanoma on his left lower
      back, a 51 year old man developed intermittently severe pain in his left
      posterior thigh. Plain X-rays showed no abnormality, but computerized tomography
      and magnetic resonance imaging scans demonstrated an abnormal soft tissue mass in
      the left sciatic notch. Although a metastasis from the original melanoma was
      suspected, exploration of the suspicious area revealed only hypertrophy of the
      left piriformis muscle. This was due to regular gymnasium exercises designed to
      selectively build up the musculature of the left lower limb, which the patient
      had undertaken in the firm belief that it would help to prevent a recurrence of
      his left-sided melanoma. Complete relief of the unilateral piriformis syndrome
      was achieved by division of the hypertrophied piriformis muscle, thereby
      relieving the pressure on the left sciatic nerve as it passed through the greater
      sciatic foramen.

PMID- 8297308
TI  - Intracranial epidural abscess: a report of three cases.
AB  - Intracranial epidural abscess is an uncommon but potentially life-threatening
      condition requiring prompt recognition and management. Most commonly it arises
      secondary to infection in the paranasal sinuses, mastoid air cells or the middle
      ear. It has also been described following craniotomy and trauma. This report
      describes three cases reported to our institution over a 15 month period, two
      associated with frontal sinusitis and one with no obvious predisposing factor.

PMID- 8297309
TI  - Intra-abdominal desmoplastic small round cell tumour.
AB  - Intra-abdominal desmoplastic small round cell tumour is a rare tumour which has
      only recently been described. It demonstrates epithelial, mesenchymal and neural
      features and has an aggressive clinical course. We report a case of a 15 year old
      male with this tumour who, after debulking surgery and chemotherapy, relapsed
      with disease 1 month later. After further debulking surgery, extensive
      chemotherapy and bone marrow transplantation he relapsed with disease 5 months
      later and died. Total survival was 20 months.

PMID- 8297310
TI  - Surgical training links between the United Kingdom and Australasia.

PMID- 8297311
TI  - Heredity, molecular genetics and colorectal cancer: a review.
AB  - It is estimated that the hereditary polyposis and non-polyposis colorectal cancer
      (CRC) syndromes, which have an autosomal dominant pattern of inheritance,
      represent less than 10% of the total CRC burden. Thus, more than 90% of all cases
      of CRC have previously been considered to arise 'sporadically', with no
      identifiable genetic link. However, recent clinical evidence now suggests that a
      significant proportion of CRC seen in the general population may involve an
      inherited genetic susceptibility. Therefore, constructing an accurate family tree
      on all patients with a family history of CRC is an essential part of identifying
      families with an increased risk for CRC who could then be offered screening.
      Also, molecular genetic study of colorectal adenomas and carcinomas has led to a
      proposed genetic model of colorectal tumorigenesis which involves interactions
      between oncogenes and tumour suppressor genes. This information has important
      potential implications for screening, determining prognosis and for providing
      multiple targets for altering the sequence of malignant transformation.

PMID- 8297312
TI  - Results of multiple strictureplasties in diffuse Crohn's disease of the small
      bowel.
AB  - With extensive small bowel strictures due to Crohn's disease, resectional surgery
      may lead to short bowel syndrome. Strictureplasty (SP) has emerged as a useful
      alternative for selected strictures. This study reviews the results of 42
      patients with diffuse obstructive Crohn's disease of the small bowel in whom at
      least four SP were performed in each patient (median: 7; range: 4-15; total SP:
      315). Twenty-three patients (55%) had had 1-5 previous small bowel resections. Co
      existing perforative disease was present in four patients (10%). Synchronous
      resection of a separate segment of small bowel was performed in 22 patients
      (52%). There was no operative mortality. Enterocutaneous fistula and/or intra
      abdominal abscess developed in three patients (7%) and only one of these needed
      operative intervention. The median follow-up was 3 years (range: 10 months to 7
      years). After SP, all patients experienced relief from obstructive symptoms. The
      median weight gain was 3 kg (range: -1-21 kg) and more than half the patients
      were weaned off steroids. Symptomatic recurrence occurred in 10 patients (24%)
      and was due to strictures (N = 9) and/or perforative disease (N = 2) at new
      site(s) unrelated to previous SP. Rate of symptomatic restricture of the SP site
      was 1.6% and was associated with new strictures elsewhere in all cases. Thus, in
      selected cases, SP is a safe and effective treatment for diffuse Crohn's
      strictures.

PMID- 8297313
TI  - Effects of catecholaminergic depletion of the amygdala and insular cortex on the
      potentiation of odor by taste aversions.
AB  - This experiment examined the effects of catecholamine depletion of the amygdala
      or insular cortex on the acquisition of olfactory and gustatory learning tasks.
      Bilateral lesions with 6-hydroxydopamine (4 micrograms/0.5 microliters) were done
      in either amygdala or insular cortex of Wistar male rats, with two groups
      receiving sham lesions. All four groups of animals were trained and tested in the
      potentiation of odor by taste aversion paradigm. The results showed that the
      amygdala-lesioned group acquired the taste, but not hte odor aversion, while the
      insular cortex-lesioned group acquired odor, but not taste aversion. Both sham
      groups showed strong taste and odor aversions. Catecholamine levels in both
      lesioned groups were significantly lower than those in the sham groups. These
      results suggest that catecholamines are necessary in the insular cortex for the
      acquisition of taste and in the amygdala for the acquisition of odor aversion in
      the potentiation of odor by taste aversion paradigm.

PMID- 8297314
TI  - Glucose enhancement of memory is not state-dependent.
AB  - Immediate post-training intraperitoneal administration of alpha-D[+]-glucose (10
      300 mg/kg) significantly enhanced retention of male Swiss mice tested 24 h after
      training in an inhibitory avoidance task. The dose-response curve was an inverted
      U in this range of dose. However, of the doses tested, only 30 mg/kg was
      effective. Glucose did not affect response latencies in mice not given the
      footshock on the training trial, suggesting that the actions of glucose on
      retention performance were not due to nonspecific effects on response latencies.
      The influence of glucose (30 mg/kg) was time-dependent, which suggests that
      glucose facilitated memory consolidation processes. Administration of glucose (30
      mg/kg) 2 or 10 min prior to the retention test did not affect the retention
      performance of mice given post-training injections of either saline or glucose
      (30 mg/kg). These findings indicate that the memory-enhancing effects of post
      training administration of glucose are not state-dependent and are consistent
      with the view that the behavioral effects of glucose are mediated through an
      interaction with the neural or neurohumoral processes underlying the storage of
      acquired information.

PMID- 8297315
TI  - Evoked ink release in Aplysia produces inhibition of the siphon withdrawal reflex
      in neighboring conspecifics.
AB  - Aplysia californica exhibit a dramatic defensive reaction, the release of a cloud
      of dark purple ink, in response to noxious stimuli. Although the neural control
      of this behavior has been studied rather extensively, the functional significance
      of the inking response is not well understood. We have found that ink released by
      animals that are subjected to noxious stimuli rapidly induces inhibition of the
      tail-elicited siphon withdrawal reflex in neighboring Aplysia. Further
      experiments indicated that the inhibitor is the ink itself, and not some other
      substance released by the donor animals. Finally, we examined whether ink-induced
      inhibition of siphon withdrawal might be a secondary consequence of an elevated
      competing response such as increased locomotion. We found that locomotion is not
      affected by the concentrations of ink we employed, indicating that the ink
      probably modulates the withdrawal reflex directly. Because the neural circuits
      responsible for both tail-elicited siphon withdrawal and the inking response have
      already been partly delineated, one can now bring the neurobiological advantages
      of Aplysia to bear on the ethologically important issue of signaling between
      conspecifics.

PMID- 8297316
TI  - NMDA receptor blockers facilitate and impair learning via different mechanisms.
AB  - The NMDA receptor blockers CGP 37849 (competitive) and MK 801 (noncompetitive)
      improve retention performance in the step-down passive avoidance situation but
      impair it in the step-through dark avoidance. It is suggested that the drugs in
      the two tasks act on different underlying processes. Whereas the memory
      facilitating effects of both drugs can be suppressed by pretreatment with either
      aldosterone or corticosterone, their negative effects on retention were steroid
      insensitive. This set of results suggests that the mechanisms by which NMDA
      blockers improve memory are different from the mechanisms by which they block
      memory.

PMID- 8297317
TI  - Effect of the calcium channel blocker amlodipine on memory in mice.
AB  - Five experiments were performed to investigate the effects of amlodipine, a
      calcium channel antagonist of the 1,4-dihydropyridine class, on consolidation and
      retrieval of memory in mice. In a single-trial passive avoidance task, amlodipine
      was administered pretraining, posttraining, or pretesting. Results of temporal
      and dose-response studies showed that memory enhancement (significant increase in
      step-through latency) occurred when amlodipine (5, 7, 9, 15, and 30 mg/kg) was
      given either immediately post-training or (15 mg/kg) 15 min pretesting. Using a
      conditioned emotional response task, tone was paired with shock using Pavlovian
      conditioning procedures. Strength of conditioning was assessed by measuring
      suppression of drinking in the presence of a tone. Amlodipine (7 mg/kg) given
      immediately following both high- and low-intensity shock significantly enhanced
      conditioned suppression. In the third experiment thirsty mice were trained on a
      spatial discrimination task in a linear maze. Correct choices were reinforced
      with liquid reinforcement. Amlodipine (10 mg/kg) injected immediately after the
      training session produced a significant enhancement of discrimination performance
      on a 24-h retention test. In the fourth experiment mice were given 25 training
      trials in a two-way active avoidance task and were treated with either amlodipine
      (10 mg/kg) or saline after training. Amlodipine-treated mice made significantly
      more avoidances on the test session than control animals. The final experiment
      demonstrated that the deficit in approach-avoidance behavior seen in 18-month-old
      mice could be reversed by amlodipine treatment after the training session. These
      studies suggest that amlodipine can facilitate memory consolidation and
      retrieval.

PMID- 8297318
TI  - Early experience effects on the development of fear in the squirrel monkey.
AB  - This study was conducted to determine whether juvenile squirrel monkeys exposed
      to a snake for a 60-min episode during the preweaning period display behavioral
      and physiological responses to a snake similar to those displayed by feral-born
      adult monkeys. Juvenile male monkeys born to feral mothers in the lab were either
      exposed to a live snake during infancy or were snake-naive. Simultaneously tested
      were adult feral-born and adult lab-born (snake-naive) males. Juveniles exposed
      as infants to a snake displayed behavioral responses and plasma cortisol
      elevations following exposure to the snake that were similar to those of feral
      born adults. In contrast, the snake-naive monkeys, regardless of age, rarely
      vocalized at the snake and displayed lower plasma cortisol elevations. These
      behavioral and physiological responses did not appear to be elicited by a moving
      animate stimulus per se, insofar as exposure to a moving fish elicited minimal
      behavioral changes and no cortisol elevations. In contrast to previous findings,
      these studies indicate that lab-born snake-naive squirrel monkeys are responsive
      to snakes, but that experience with snakes in infancy produces behavioral and
      physiological responses more similar to those observed in feral-born monkeys.

PMID- 8297319
TI  - Sensory control of the male rat's copulatory thrusting patterns.
AB  - The effects of reduced somatosensory feedback from the penis and/or the preputial
      region upon the male rat's copulatory thrusting patterns and sexual behavior were
      analyzed. Copulatory thrusting was recorded with an accelerometric technique
      allowing for the determination of duration and frequency of the thrusting trains.
      Section of the dorsal penile nerves (denervation) or lidocaine applied to the
      distal part of the penis reduced the number of intromissions and the intromission
      ratio. These treatments had no effect on copulatory thrusting patterns. Lidocaine
      injected into the preputial region also reduced the number of intromissions and
      the intromission ratio. Moreover, the number of disorganized mounts, as revealed
      by the accelerometric record, was much increased by this treatment. In addition,
      the duration of the thrusting trains associated with mount and intromission was
      increased. No effect was found on thrusting frequency. These data suggest that
      somatosensory feedback from the penis is critical for the achievement of
      intromission, whereas feedback from the preputial region is important for the
      execution of copulatory thrusting. Furthermore, it is possible that the strong
      sensory stimulation of the prepuce associated with penile insertion participates
      in the termination of thrusting and penile withdrawal.

PMID- 8297320
TI  - Behavioral analysis of asymmetries induced by unilateral 6-OHDA injections into
      the substantia nigra.
AB  - The intent of this study was to perform a detailed analysis of behavioral
      asymmetries (turning behavior) exhibited by animals which had sustained a
      unilateral lesion of the substantia nigra (SN). Rats were tested for behavior
      asymmetries over 16 days, once before, and 7 times after 6-OHDA had been injected
      into one SN. On the basis of the number of narrow diameter ipsiversive half turns
      produced during testing, they were then assigned to one of three groups: (a)
      those which showed an initial asymmetry from which they recovered, (b) those
      which were asymmetrical throughout testing, and (c) those in which the asymmetry
      only emerged during the testing period. We examined several different aspects of
      turning behavior. Recovery from asymmetry was associated with an increase in the
      number of contraversive, as well as a decrease in the number of ipsiversive
      narrow-angle turns. The average diameter of these ipsiversive turns also
      increased. Animals which recovered showed a contraversive asymmetry for wide
      diameter turns which increased during testing. Narrow-diameter contraversive
      turns decreased during testing in the two nonrecovery groups. Both nonrecovery
      groups showed a contraversive asymmetry for wide-diameter turns. Asymmetry was
      attributable to a tendency to circle and move ipsiversively in the two
      nonrecovery groups, whereas it was due to circling behavior in animals which
      showed recovery. Additionally, more cells, labeled by HRP injected into the
      ipsilateral caudate putamen, were found in the damaged SN of animals which
      recovered.

PMID- 8297321
TI  - Alteration of the bed nucleus of the stria terminalis (BNST) in young female
      Djungarian hamsters (Phodopus campbelli) exposed to adult males.
AB  - Central components of the vomeronasal system appear to mediate extrahypothalamic
      control of gonadotropin release during male-induced acceleration of puberty onset
      in female rodents. In order to describe the bed nucleus of the stria terminalis
      (BNST) and to determine whether this component of the vomeronasal system is
      altered following early puberty onset, the anterior BNST of female Djungarian
      hamsters (Phodopus campbelli) was subdivided into three regions: medial, lateral,
      and ventral. The cross-sectional area, soma size, and neuronal density of each
      subdivision was compared among female hamsters in three groups: (1) young females
      showing accelerated reproductive development following a period of housing with
      an adult male, (2) young females matched by age with the accelerated females but
      housed alone during the same period, and (3) older females at the age of
      spontaneous puberty. Females housed with an adult male and undergoing accelerated
      puberty onset had significantly smaller lateral anterior BNST subdivisions than
      females housed alone for the same period (10 days following weaning) or housed
      alone until the age of spontaneous puberty onset (25 days following weaning). The
      size of the ventral and medial subdivisions was not different in the three
      groups. Furthermore, although soma size and neuronal density differed markedly
      among the anterior BNST subdivisions, these subdivision characteristics were
      similar in the accelerated, prepubertal, and older pubertal females. Our finding
      demonstrates that a central component of the vomeronasal system undergoes
      neuroanatomical alteration in response to environmental stimuli and recommends
      further examination of the BNST during this dynamic ontogenetic period.

PMID- 8297322
TI  - Visual cortex ablations do not prevent extinction of fear-potentiated startle
      using a visual conditioned stimulus.
AB  - Following observations in the literature that sensory cortex ablations prevent
      extinction of conditioned fear, the present experiments tested the generality of
      this finding by examining whether visual cortex ablations would prevent
      extinction of conditioned fear as assessed by fear-potentiated startle using a
      visual conditioned stimulus. Consistent with previous reports, visual cortex
      ablations did not prevent the acquisition or expression of fear-potentiated
      startle to a visual conditioned stimulus. More importantly, visual cortex
      ablations did not prevent extinction of fear-potentiated startle to a visual
      conditioned stimulus, nor did they reverse preoperatively established extinction,
      indicating that sensory cortex is not required for extinction of conditioned fear
      in all situations.

PMID- 8297323
TI  - The effect of US preexposure on conditioned taste aversion: lack of
      postconditioning recovery of the aversion.
AB  - Although the CS preexposure effect in CTA was once viewed exclusively as an
      acquisition failure, recent studies have suggested that the latent inhibition
      phenomenon is the result of retrieval impairment. This interpretive challenge is
      based on the unexpected finding that recovery of the aversion occurs over a long
      retention interval following conditioning (Kraemer, Lariviere, & Spear, Animal
      Learning and Behavior, 16, 185-190, 1988; Bakner, Strohen, Nordeen, & Riccio,
      Physiology & Behavior, 50, 1269-1272, 1991). This study examined whether a
      similar recovery occurs after US preexposure. Following preexposure to the US
      (LiCl), rats received a sucrose-illness pairing and were subsequently tested
      after either short or long training-to-test intervals. In contrast to the
      findings with the CS preexposure effect, US-preexposed subjects did not show a
      spontaneous increase in CTA following the long retention interval.

PMID- 8297324
TI  - Lead exposure and latent learning ability of adult female rats.
AB  - The present report investigates the effects of lead exposure during the pre- and
      postnatal period on the latent learning ability in a maze. Rats were submitted to
      lead acetate intoxication by giving their dams 0.5, 1.0, or 4.0 mM lead acetate
      or deionized water. Rats were weaned at 21 days, and the treatment was continued
      by giving the same solution of lead acetate in the drinking water until
      behavioral testing. Under a nonappetitive condition, rats were exposed either to
      an open field or to a maze apparatus. They were thereafter deprived of food and
      tested in the maze apparatus. Lead treatment induced an increase in locomotor
      activity in the open field during training sessions, and animals failed to
      habituate to the environment. Nevertheless, both lead-treated and control rats
      that had been previously exposed to the maze performed better than those exposed
      to the open field. These results suggest that rats intoxicated with lead are able
      to learn about the environment when no immediate reinforcement is involved.

PMID- 8297325
TI  - Sexual experience and preferences for odors of estrous females in staggerer
      mutant male mice.
AB  - Staggerer mutant male mice generally do not mate and olfactory disabilities may
      be involved. Choice tests were used to determine the preference of C57BL/6 male
      mice with the staggerer mutation for urine and vaginal secretions from receptive
      and unreceptive females. The staggerer mutation does not prevent the olfactory
      discrimination between vaginal secretions of estrous and anestrous females. Male
      preferences for odors of receptive females are related to the presence of sexual
      experience.

PMID- 8297326
TI  - Impaired short-term memory resulting from postnatal undernutrition is attenuated
      by physostigmine.
AB  - Early-life undernutrition impairs the short-term memory capacity of adult rats
      (90 days of age) trained on a conditional-spatial discrimination task (Castro,
      Tracy, & Rudy, Behavioral Brain Research, 32, 255-264, 1989). While well
      nourished control animals perform above 90% correct when the interval separating
      the forced run and choice run is 180 s, the performance of the undernourished
      animals falls to chance (50%) when the delay interval is increased to 90 s. We
      now report that this performance decrement can be attenuated by the
      administration of the anticholinesterase, physostigmine. However, the effects of
      physostigmine were dose dependent. While 0.02 mg/kg of physostigmine improved the
      performance of the undernourished animals so that they performed significantly
      above chance at the 180-s delay interval, neither 0.2 nor 0.002 mg/kg of
      physostigmine improved performance. We concluded that this effect was centrally
      mediated since scopolamine hydrobromide (1.0 mg/kg) which blocks both central and
      peripheral cholinergic receptors blocked physostigmine's performance-improving
      effect, while methyl-scopolamine (1.0 mg/kg) which blocks only peripheral
      receptors did not. These are the first results which suggest that the short-term
      memory impairments produced by early-life undernutrition can be attenuated by
      enhancing central cholinergic functioning.

PMID- 8297328
TI  - Nitrogenase of Klebsiella pneumoniae: electron nuclear double resonance (ENDOR)
      studies on the substrate reduction site.
AB  - Proton electron nuclear double resonance (ENDOR) spectra from the iron-molybdenum
      cofactor (FeMoco) of Klebsiella pneumoniae nitrogenase bound to the enzyme show
      that a wide variety of substrates and inhibitors, including dinitrogen, acetylene
      and cyanide, do not bind at or close to FeMoco in the dithionite-reduced state of
      the free MoFe protein, in agreement with our previous kinetic studies. Therefore
      models for substrate binding to FeMoco must consider structures at a more reduced
      level than that described by Kim and Rees [(1992) Science 257, 1677-1682]. After
      the enzyme has turned over in the presence of 2H2O, an additional set of protons
      are potentially available for exchange, namely those that can give rise to
      dihydrogen during enzyme turnover or generate the hydridic dinitrogen binding
      site; such exchangeable protons were not observed. They cannot therefore be
      proposed in order to explain the unusual geometry of the 'trigonal iron atoms'
      observed in the structure of FeMoco.

PMID- 8297327
TI  - The structure and function of proline-rich regions in proteins.

PMID- 8297329
TI  - Simultaneous oscillations of cytoplasmic free Ca2+ concentration and Ins(1,4,5)P3
      concentration in mouse pancreatic beta-cells.
AB  - Changes in the cytoplasmic free Ca2+ concentration ([Ca2+]i) in stimulated cells
      are often oscillatory, but the mechanisms that drive these oscillations are still
      a matter of controversy: different models of the generation of these [Ca2+]i
      oscillations make different assumptions as to whether oscillations in
      Ins(1,4,5)P3 concentration are necessary for this process. We have looked for
      changes in inositol polyphosphate levels that might occur in suspensions of
      murine pancreatic beta-cells when these cells are induced to display synchronized
      oscillations in [Ca2+]i by the sequential addition of glucose, an alpha 2
      adrenergic stimulus and extracellular Ca2+. The intracellular level of
      Ins(1,4,5)P3 oscillated in a manner approximately in synchrony with changes in
      [Ca2+]i. Oscillations in the levels of Ins(1,4,5)P3 metabolites [Ins(1,3,4)P3 and
      inositol bisphosphates] were slightly delayed relative to the Ins(1,4,5)P3
      oscillations, and the concentration of Ins(1,3,4,5,6)P5 remained approximately
      constant during the [Ca2+]i oscillations. These results demonstrate that
      [Ins(1,4,5)P3] and [Ca2+]i oscillate in synchrony in at least one type of cell.
      Whether such oscillations in intracellular [Ins(1,4,5)P3] provide a primary
      driving force for [Ca2+]i oscillations either in beta-cells or in other
      stimulated cells remains to be determined. Even if they do not, the
      [Ins(1,4,5)P3] oscillations will at least provide an amplifying influence on the
      [Ca2+]i changes.

PMID- 8297330
TI  - Cathepsin G and thrombin: evidence for two different platelet receptors.
AB  - Neutrophil cathepsin G and thrombin, the only platelet agonists that are
      proteases, exhibit a mandatory requirement for catalytic activity to induce
      platelet aggregation and signal transduction. The thrombin receptor is a G
      protein-coupled receptor which undergoes proteolysis to generate a tethered
      ligand that causes self-activation. Since cathepsin G strongly resembles thrombin
      in its ability to activate platelets, we have attempted to determine whether
      cathepsin G and thrombin function through the same or different receptors.
      Evidence that thrombin and cathepsin G act at different receptors was as follows:
      (a) an antibody directed against the thrombin receptor blocked thrombin-induced
      but not cathepsin G-induced platelet responses; (b) human fibroblasts responded
      to thrombin and to a synthetic thrombin receptor peptide (comprising residues 42
      55 of the thrombin receptor) by exhibiting an elevation in cytosolic Ca2+
      concentration but did not respond to cathepsin G; and (c) platelets pretreated
      with neutrophil elastase failed to respond to thrombin but responded when
      rechallenged by cathepsin G. Thrombin and cathepsin G exhibit heterologous
      desensitization that is potentiated by okadaic acid and is attenuated by
      staurosporine, indicating that phosphorylation of serine/threonine residues is
      important for desensitization and that protein kinase C may be involved. Since
      catalytic activity of cathepsin G is required for platelet stimulation, it is
      probable that platelet activation by cathepsin G requires receptor proteolysis
      and that a tethered ligand mechanism is involved, suggesting that platelets may
      possess a family of protease receptors.

PMID- 8297331
TI  - Microsomal lipoamide reductase provides vitamin K epoxide reductase with reducing
      equivalents.
AB  - This study was undertaken to search for the endogenous dithiol cofactor of the
      reductases of the vitamin K cycle. As a starting point, the redox-active
      lipophilic endogenous compounds lipoic acid and lipoamide were looked at. The
      study shows that microsomes contain NADH-dependent lipoamide reductase activity.
      Reduced lipoamide stimulates microsomal vitamin K epoxide reduction with kinetics
      comparable with those for the synthetic dithiol dithiothreitol (DTT). Reduced
      lipoic acid shows higher (4-fold) Km values. No reductase activity with lipoic
      acid was found to be present in microsomes or cytosol. The reduced-lipoamide
      stimulated vitamin K epoxide reductase is as sensitive to warfarin and salicylate
      inhibition as is the DTT-stimulated one. Both vitamin K epoxide reductase and
      lipoamide reductase activity are recovered in the rough microsomes.
      NADH/lipoamide-stimulated vitamin K epoxide reduction is uncoupled by traces of
      Triton X-100, suggesting that microsomal lipoamide reductase and vitamin K
      epoxide reductase are associated. The results suggest that the vitamin K cycle
      obtains reducing equivalents from NADH through microsomal lipoamide reductase.

PMID- 8297332
TI  - Effect of specificity on ligand conformation in acyl-chymotrypsins.
AB  - I.r. difference spectroscopy combined with 13C and 18O double-isotope
      substitution was used to examine the ester acyl carbonyl stretching vibration of
      hydrocinnamoyl-chymotrypsin. A single acyl carbonyl stretching band was observed
      at 1731 cm-1. This contrasts with previous i.r. and resonance Raman spectroscopic
      studies of a number of trans-3-arylacryloyl-chymotrypsins which showed two acyl
      carbonyl stretching bands in the region of 1700 cm-1, which were proposed to
      represent productive and non-productive conformations of the acyl-enzyme. The
      single acyl carbonyl band for hydrocinnamoyl-chymotrypsin suggests only a single
      conformation, and the comparatively high frequency of this band implies little or
      no hydrogen-bonding to this carbonyl group. Enzymic hydrogen-bonding to the acyl
      carbonyl is believed to give bond polarization and thereby catalytic-rate
      acceleration. Thus, in view of the apparent lack of such hydrogen-bonding in
      hydrocinnamoyl-chymotrypsin, it should be the case that this acyl-chymotrypsin is
      less specific than trans-3-arylacryloyl-chymotrypsins, whereas the opposite is
      true. It is therefore proposed that there may be a productive acyl carbonyl
      population of lower stretching frequency for hydrocinnamoyl-chymotrypsin, but
      that this is too small to be discerned because of either a relatively high
      deacylation rate or an unfavourable conformational equilibrium. The single acyl
      carbonyl band for hydrocinnamoyl-chymotrypsin is significantly broader than those
      for trans-3-arylacryloyl-chymotrypsins, indicating that this group is more
      conformationally mobile and dispersed in the former. This can be correlated with
      the absence of acyl carbonyl hydrogen-bonding in hydrocinnamoyl-chymotrypsin, and
      with the much greater flexibility of the saturated hydrocinnamoyl group than
      unsaturated trans-3-arylacryloyl. This flexibility is presumably the reason why
      hydrocinnamoyl-chymotrypsin is more specific than trans-3-arylacryloyl
      chymotrypsins. Resonance Raman spectroscopy is limited to the non-specific trans
      3-arylacryloyl-chymotrypsins because of its chromophoric requirement, whereas
      i.r. may be used to examine non-chromophoric more specific acyl-enzymes such as
      hydrocinnamoyl-chymotrypsin. The results presented in this paper suggest that
      trans-3-arylacryloyl-chymotrypsins are atypical.

PMID- 8297334
TI  - In vitro splicing of pre-messenger RNA with extracts from 5-fluorouridine-treated
      cells.
AB  - The effect of 5-fluorouridine (5-FU) treatment of cells on the splicing of pre
      mRNA was determined using cellular extracts and splicing in vitro. Nuclear
      extracts from control cells and cells treated with 5-FU were prepared and used to
      splice pre-mRNAs in vitro. The drug treatment resulted in inhibition of cell
      growth but had little effect on RNA synthesis. The extracts from 5-FU-treated
      cells showed significant inhibition of splicing. This inhibition was the result
      of reduced efficiency and was not caused by a block at a specific step in the
      splicing pathway. There were no observable changes in the levels or physical
      properties of the small nuclear ribonucleoprotein particles that are essential
      cofactors in the splicing process. The deficiency in splicing in the extracts
      from 5-FU-treated cells could be supplemented by the addition of complementary
      fractions from a control extract.

PMID- 8297333
TI  - Structural disruption of the trans-Golgi network does not interfere with the
      acute stimulation of glucose and amino acid uptake by insulin-like growth factor
      I in muscle cells.
AB  - The effects of insulin-like growth factor I (IGF-I) on glucose and amino acid
      uptake were investigated in fully differentiated L6 muscle cells, in order to
      determine whether the two processes are functionally related. Transport of both
      glucose and amino acid (methylaminoisobutyric acid, MeAIB) was activated rapidly
      in response to IGF-I. Stimulation reached a peak within 30 min and was sustained
      for up to 90 min. Maximal activation of either glucose or MeAIB transport was
      achieved at 3 nM IGF-I; the half-maximal activation (ED50) of glucose transport
      was at 107 pM and that of MeAIB transport was at 36 pM. Stimulation of amino acid
      uptake occurred in the absence or presence of glucose, suggesting that this
      response is not secondary to increased glucose intake. Incubation of cells for 1
      h with Brefeldin A (5 micrograms/ml), which disassembles the Golgi apparatus and
      inhibits the secretory pathway in eukaryotic cells, had no effect on the acute
      IGF-I activation of glucose and MeAIB transport. Moreover, Brefeldin A caused
      wide redistribution of the trans-Golgi antigen TGN38, as assessed by subcellular
      fractionation, without affecting the distribution of glucose transporters. The
      finding that the degree of activation, time response and sensitivity to IGF-I and
      Brefeldin A were similar for both glucose and MeAIB transport suggests
      commonalities in the IGF-I mechanism of recruitment of glucose transporters and
      stimulation of amino acid transport through System A. An integral trans-Golgi
      network does not appear to be required for the acute IGF-I stimulation of glucose
      or amino acid transport, even though stimulation of glucose transport occurs
      through recruitment of glucose transporters from intracellular stores in these
      cells. We propose that the donor site of glucose transporters (and perhaps of
      amino acid transporters) involved in the acute response to IGF-I lies beyond the
      trans-Golgi network, perhaps in an endosomal compartment in close proximity to
      the plasma membrane.

PMID- 8297335
TI  - Isolation and expression of a novel chick G-protein cDNA coding for a G alpha i3
      protein with a G alpha 0 N-terminus.
AB  - We have cloned cDNAs coding for G-protein alpha subunits from a chick brain cDNA
      library. Based on sequence similarity to G-protein alpha subunits from other
      eukaryotes, one clone was designated G alpha i3. A second clone, G alpha i3-o,
      was identical to the G alpha i3 clone over 932 bases on the 3' end. The 5' end of
      G alpha i3-o, however, contained an alternative sequence in which the first 45
      amino acids coded for are 100% identical to the conserved N-terminus of G alpha o
      from species such as rat, mouse, human, bovine and hamster. Both clones were
      found to be expressed in all tissues studied. The unusual alpha o-alpha i3-like G
      protein chimera, G alpha i3-o, was found to be expressed at significantly lower
      levels than G alpha i3. In vitro transcription and translation of the G alpha i3
      o cDNA clone gave a protein of approx. 41 kDa which stably bound guanosine 5'
      [gamma-thio]triphosphate. G alpha i3-o appears to be the first G-protein alpha
      subunit cloned which contains ends that are homologous to two different alpha
      subunit isoforms, G alpha o and G alpha i3.

PMID- 8297336
TI  - Effect of retinoic acid on mucin gene expression in rat airways in vitro.
AB  - Ultrastructural examination of rat tracheal explants at various times of culture
      in a serum-free and hormone-supplemented medium containing retinoic acid showed
      that the cytological characteristics of the epithelium were well preserved for at
      least 192 h. Hybridization analyses for mucin core protein mRNA in the explants
      were performed with a 30-base oligonucleotide probe, the design of which was
      based on the tandem repeat sequence of the rat intestine mucin core protein. The
      probe reacted with total RNA prepared from trachea, intestine and colon, but not
      with total RNA obtained from liver or alveolar region of the lung. Type-I keratin
      expression was observed in the explant grown at different periods of time in a
      medium with and without retinoic acid. The hybridization probe gave a prominent
      reaction with RNA preparations obtained from tracheal explants incubated for as
      long as 192 h in a medium containing retinoic acid. In the absence of retinoic
      acid, however, the mucin message was evident at the 24 h time point but
      thereafter decreased to barely detectable levels. When retinoic acid was added at
      96 h to the latter cultures, the mucin mRNA was prominent again after additional
      incubation for 24 and 48 h. Northern-blot analyses of tracheal RNA showed a
      diffuse band at approx. 7.5 kb. Addition of a variety of chemical and
      pharmacological agents to explants cultured in the presence of retinoic acid had
      no dramatic induction or inhibitory effects on the mucin mRNA. Only the steroid
      prednisolone had a reproducible inhibitory effect.

PMID- 8297337
TI  - Constitutive expression of a saturable transport system for non-esterified fatty
      acids in Xenopus laevis oocytes.
AB  - In the presence of 150 microM BSA, uptake of [3H]oleate by Xenopus laevis oocytes
      was a saturable function of the unbound oleate concentration (Vmax. 110 +/- 4
      pmol/h per oocyte; Km 193 +/- 11 nM unbound oleate). Oleate uptake was three
      orders of magnitude faster than that of another test substance,
      [35S]bromosulphophthalein, and was competitively inhibited by 55 nM unbound
      palmitate (Vmax. 111 +/- 14 pmol/h per oocyte; Km 424 +/- 63 nM unbound oleate)
      (P < 0.01). Oleate uptake was also inhibited by antibodies to a 43 kDa rat liver
      plasma-membrane fatty acid-binding protein, a putative transporter of long-chain
      fatty acids in mammalian cells; uptake of the medium-chain fatty acid
      [14C]octanoate was unaffected. Immunofluorescence and immunoblotting demonstrated
      that the antiserum reacted with a single 43 kDa protein on the oocyte surface.
      Hence a protein related to the mammalian plasma-membrane fatty acid-binding
      protein may play a role in saturable uptake of long-chain fatty acids by Xenopus
      oocytes.

PMID- 8297338
TI  - Low-density lipoprotein as a transporter of dolichol intermediates in the
      mammalian circulation.
AB  - The cholesteryl esters which make up the bulk of the core of the human low
      density lipoprotein particle were removed by extraction into heptane and replaced
      with the fluorescent anthroyl or N-(7-nitrobenzyl-2-oxa-1,3-diazol-4
      yl)aminohexanoyl esters of dolichol. The reconstituted low-density lipoproteins
      were efficiently internalized by normocholesterolaemic human fibroblasts but not
      by fibroblasts from patients lacking the low-density-lipoprotein receptor, or
      lacking the ability to internalize the receptor-lipoprotein complex. In normal
      fibroblasts, the reconstituted low-density lipoproteins were delivered to
      lysosomes after internalization. The results suggest that (i) dolichol
      intermediates in the human circulation are normally carried on low-density
      lipoproteins and (ii) that low-density lipoproteins are involved in the
      accumulation of dolichol intermediates in lysosomes during normal human aging and
      in certain diseases involving the lysosome. In addition, by incorporating these
      very hydrophobic probes into low-density lipoprotein, they can be presented to
      cells in culture at high concentration in a water-soluble form.

PMID- 8297339
TI  - Steady-state kinetics of malonyl-CoA synthetase from Bradyrhizobium japonicum and
      evidence for malonyl-AMP formation in the reaction.
AB  - Malonyl-CoA synthetase catalyses the formation of malonyl-CoA directly from
      malonate and CoA with hydrolysis of ATP into AMP and PP1. The catalytic mechanism
      of malonyl-CoA synthetase from Bradyrhizobium japonicum was investigated by
      steady-state kinetics. Initial-velocity studies and the product-inhibition
      studies with AMP and PPi strongly suggested ordered Bi Uni Uni Bi Ping Pong Ter
      Ter system as the most probable steady-state kinetic mechanism of malonyl-CoA
      synthetase. Michaelis constants were 61 microM, 260 microM and 42 microM for ATP,
      malonate and CoA respectively, and the value for Vmax, was 11.2 microM/min. The
      t.l.c. analysis of the 32P-labelled products in a reaction mixture containing
      [gamma-32P]ATP in the absence of CoA showed that PPi was produced after the
      sequential addition of ATP and malonate. Formation of malonyl-AMP, suggested as
      an intermediate in the kinetically deduced mechanism, was confirmed by the
      analysis of 31P-n.m.r. spectra of an AMP product isolated from the 18O-transfer
      experiment using [18O]malonate. The 31P-n.m.r. signal of the AMP product appeared
      at 0.024 p.p.m. apart from that of [16O4]AMP, indicating that one atom of 18O
      transferred from [18O]malonate to AMP through the formation of malonyl-AMP.
      Formation of malonyl-AMP was also confirmed through the t.l.c. analysis of
      reaction mixture containing [alpha-32P]ATP. These results strongly support the
      ordered Bi Uni Uni Bi Pin Pong Ter Ter mechanism deduced from initial-velocity
      and product-inhibition studies.

PMID- 8297340
TI  - Association of the insulin receptor and phosphatidylinositol 3-kinase requires a
      third component.
AB  - We have studied the interactions between the insulin receptor and PtdIns 3-kinase
      by a reconstitution system in vitro composed of highly purified PtdIns 3-kinase
      from rat liver and highly purified insulin receptors bound to insulin-agarose or
      to antibodies against insulin receptors. As a positive control, receptors for
      platelet-derived growth factor, which bind and phosphorylate PtdIns 3-kinase,
      were studied in parallel with insulin receptors. Our results indicate that the
      insulin receptor, regardless of its phosphorylation state, does not directly
      associate with purified PtdIns 3-kinase, whereas the autophosphorylated receptor
      does associate with PtdIns 3-kinase present in the crude CHO-cell lysate. Also,
      we could not detect phosphorylation of PtdIns 3-kinase by the insulin receptor,
      even through the receptor readily underwent autophosphorylation and
      phosphorylated an insulin-receptor substrate, poly(Glu-Tyr) (4:1). These findings
      argue that one or more cytosolic components link the receptor and the enzyme.
      Insulin-receptor substrate-1 (IRS-1) was evaluated as a potential linking
      protein. In the absence of ATP, IRS-1 did not facilitate the coupling of the
      phosphorylated insulin receptor to PtdIns 3-kinase. Thus IRS-1 is unlikely to be
      the component in crude CHO-cell lysate that couples PtdIns 3-kinase to the
      phosphorylated insulin receptor. However, the addition of ATP, which allows
      phosphorylation of IRS-1 by the insulin receptor, also enhances the coupling of
      PtdIns 3-kinase to the insulin receptor. In support of this idea,
      immunoprecipitates of IRS-1 from insulin-treated CHO cells were found to contain
      both the insulin receptor and PtdIns 3-kinase. In conclusion, the insulin
      receptor does not appear to phosphorylate or bind directly to PtdIns 3-kinase,
      regardless of the receptor's state of phosphorylation. Association of PtdIns 3
      kinase with the insulin receptor is mediated by one or more components, one of
      which may involve an unidentified factor in cell lysate and another that
      apparently involves phosphorylated IRS-1.

PMID- 8297342
TI  - Structural features of the exocellular polysaccharides of Mycobacterium
      tuberculosis.
AB  - The cell envelope which surrounds pathogenic mycobacteria is postulated to be a
      defence barrier against phagocytic cells and its outermost constituents have a
      tendency to accumulate in the culture medium. The present work demonstrates that
      the exocellular material of Mycobacterium tuberculosis contains large amounts of
      polysaccharides with only traces, if any at all, of lipids. Three types of
      polysaccharides were purified by anion-exchange and gel-filtration
      chromatography; all were found to be neutral compounds devoid of acyl
      substituents. They consisted of D-glucan, D-arabino-D-mannan and D-mannan, which
      were eluted from gel-filtration columns in positions corresponding to molecular
      masses of 123, 13 and 4 kDa respectively. Their predominant structural features
      were determined by the characterization of the per-O-methyl derivatives of
      enzymic, acetolysis and Smith-degradation products and by 1H- and 13C-n.m.r.
      spectroscopy of the purified polysaccharides, using mono- and two-dimensional
      homonuclear chemical-shift correlated spectroscopy and two-dimensional
      heteronuclear (1H/13C) spectroscopy. The glucan which represented up to 90% of
      the polysaccharides was composed of repeating units of five or six-->4-alpha-D
      Glcp-1--> residues and a -->4-alpha-D-Glcp substituted at position 6 with an
      alpha-D-Glcp, indicating a glycogen-like highly branched structure not related to
      the so-called polysaccharide-II previously identified in tuberculin. The
      arabinomannan consisted of a mannan segment composed of a -->6-alpha-D-Man-1-->
      core substituted at some positions 2 with an alpha-D-Manp. The arabinan termini
      of the arabinomannan were found to be extensively capped with mannosyl residues.
      The possibility that these polysaccharides contribute to the persistence of the
      tubercle bacillus in the macrophage by molecular mimicry is discussed.

PMID- 8297341
TI  - Correlated expression of the 97 kDa sarcoendoplasmic reticulum Ca(2+)-ATPase and
      Rap1B in platelets and various cell lines.
AB  - Evidence has accumulated that cyclic AMP (cAMP)-induced phosphorylation of a Ras
      related protein (Rap1) regulates platelet Ca2+ transport. As this transport was
      recently found to be controlled by two isoforms of sarcoendoplasmic reticulum
      Ca(2+)-ATPase (SERCA), the 100 kDa SERCA2b and the newly identified 97 kDa SERCA,
      we attempted to establish which isoform is involved in this regulation. For this
      purpose, we studied the expression and regulation of both the SERCA and Rap1
      isoforms in platelets, haemopoietic cells and various cancer cell lines. SERCA2b
      was shown to be equally expressed in all the cell lines tested, as determined by
      detection of its phosphoenzyme formation and by Western blotting using an isoform
      specific antibody. In contrast, the expression of the 97 kDa SERCA, studied by
      the same methods, varied from total absence in the cancer cells to high levels in
      the megakaryocytic cell lines. With regard to the potential regulatory Rap1
      proteins, Western blotting showed different expression of total Rap1 isoforms
      among the cell lineages, thus ruling out any possible relationship between Rap1
      and SERCA2b. However, the expression of Rap1 proteins correlated with that of the
      97 kDa SERCA isoform. More refined analysis of the rap1A and rap1B isoforms by
      reverse transcription PCR and by determining cAMP-induced phosphorylation of
      Rap1B, i.e. its functional mechanism, confirmed the correlation between Rap1B and
      the 97 kDa SERCA expression. This relationship was also established by the
      concerted up-regulation of these two proteins demonstrated in the pathological
      model of platelets from hypertensive rats. It is concluded that the expressions
      of 97 KDa SERCA and Rap1B are related, suggesting that regulation of the platelet
      Ca(2+)-ATPase system by cAMP-induced phosphorylation of Rap1B specifically
      involves the 97 kDa SERCA.

PMID- 8297343
TI  - Intronless celB from the anaerobic fungus Neocallimastix patriciarum encodes a
      modular family A endoglucanase.
AB  - The cDNA designated celB from the anaerobic rumen fungus Neocallimastix
      patriciarum contained a single open reading frame of 1422 bp coding for a protein
      (CelB) of M(r) 53,070. CelB expressed by Escherichia coli harbouring the full
      length gene hydrolysed carboxymethylcellulose in the manner of an endoglucanase,
      but was most active against barley beta-glucan. It also released reducing sugar
      from xylan and lichenan, but was inactive against crystalline cellulose,
      laminarin, mannan, galactan and arabinan. The rate of hydrolysis of cellulo
      oligosaccharides by CelB increased with increasing chain length from cellotriose
      to cellopentaose. The predicted structure of CelB contained features indicative
      of modular structure. The first 360 residues of CelB constituted a fully
      functional catalytic domain that was homologous with bacterial endoglucanases
      belonging to cellulase family A, including five which originate from three
      different species of anaerobic rumen bacteria. Downstream from this domain, and
      linked to it by a serine/threonine-rich hinge, was a non-catalytic domain
      containing short tandem repeats, homologous to the C-terminal repeats contained
      in xylanase A from the same anaerobic fungus. Unlike previous fungal cellulases,
      genomic celB was devoid of introns. This lack of introns and the homology of its
      encoded product with rumen bacterial endoglucanases suggest that acquisition of
      celB by the fungus may at some stage have involved horizontal gene transfer from
      a prokaryote to N. particiarum.

PMID- 8297344
TI  - Electron-paramagnetic-resonance and magnetic-circular-dichroism studies of the
      binding of cyanide and thiols to the thiols to the iron-molybdenum cofactor from
      Klebsiella pneumoniae nitrogenase.
AB  - FeMoco, a low-M(r) metal cluster of probable composition Fe7MoS9 complexed with
      homocitrate, has been extracted with N-methylformamide from the MoFe protein of
      the nitrogenase enzyme from Klebsiella pneumoniae. The binding of cyanide and
      thiols to the FeMoco cluster in its paramagnetic S = 3/2 oxidation level has been
      studied by low-temperature e.p.r. and magnetic-circular-dichroism (m.c.d.)
      spectroscopies. Cyanide binds to isolated FeMoco at more than one site, and
      causes changes in the g values form g = 4.6, 3.2, 2.0 to g = 4.29, 3.82, 2.02
      E.p.r. competition studies indicate that one cyanide can be displaced by thiolate
      from one type of site. The form of the low-temperature m.c.d. spectrum is little
      changed by ligand binding, thus the basic cluster structure remains intact.
      However, when benzenethiol is bound, a new intense band (lambda 387 nm) is
      observed, indicating the generation of an increased ligand-to-cluster charge
      transfer interaction.

PMID- 8297345
TI  - Platelet-derived growth factor (PDGF)-AB-mediated phosphorylation of PDGF beta
      receptors.
AB  - Platelet-derived growth factor (PDGF) stimulates the proliferation of Balb/c-3T3
      fibroblasts through binding and subsequent activation of PDGF receptors.
      Activation of the PDGF receptors has been proposed to involve receptor
      dimerization. PDGF-AB has been shown to bind PDGF alpha and beta receptor
      subunits to form PDGF alpha beta and alpha alpha receptor dimers. In this paper
      we demonstrate that, following the down-regulation of PDGF alpha receptors, the
      binding of PDGF-AB to beta receptors occurred at 37 degrees C but not at 4
      degrees C. PDGF-AB stimulated the phosphorylation of PDGF beta receptor monomers
      in cells depleted of PDGF alpha receptors by prior exposure to PDGF-AA.

PMID- 8297346
TI  - Platelet-derived growth factor (PDGF) BB homodimer regulates PDGF A- and PDGF B
      chain gene transcription in human mesangial cells.
AB  - Mesangial cells express platelet-derived growth factor (PDGF) A- and B-chain mRNA
      and release PDGF. Several polypeptide growth factors, including PDGF itself,
      induce PDGF A- and B- chain mRNA abundance. To understand the molecular
      mechanisms associated with the changes in mRNA abundance, we measured the effects
      of PDGF BB homodimer on PDGF A- and B-chain gene transcription in cultured
      mesangial cells. The data demonstrate 2- and 4-fold increases in PDGF A-chain
      gene transcription in response to PDGF BB homodimer at 5 and 24 h time points
      respectively. PDGF B-chain gene transcription was also induced approximately 3
      fold at 2, 5 and 24 h time points in response to treatment with PDGF BB
      homodimer. The effect of PDGF BB on the half-life of PDGF A- as well as PDGF B
      chain mRNA was measured directly by the pulse-chase method. There was no effect
      on PDGF A-chain mRNA half-life whereas PDGF B-chain mRNA half-life was increased
      1.5-fold. These studies indicate that, in human mesangial cells, the increase in
      the levels of PDGF A- and B-chain mRNA in response to PDGF- receptor(s)
      activation is mediated at the level of gene transcription. In addition, the
      regulation of PDGF B- but not PDGF A-chain gene involves increased mRNA
      stability. Mesangial cells are a useful model for studying molecular mechanisms
      of PDGF- gene regulation in non-transformed human cells.

PMID- 8297347
TI  - Molecular characterization of hNRP, a cDNA encoding a human nucleosome-assembly
      protein-I-related gene product involved in the induction of cell proliferation.
AB  - We have isolated from a human thymus cDNA library a cDNA clone encoding a
      potential protein with 54% amino acid similarity to that encoded by a previously
      identified cDNA for yeast nucleosome assembly protein I (NAP-I). The deduced
      amino acid sequence for this newly identified cDNA, designated hNRP (human NAP
      related protein), contains a potential seven-residue nuclear localization motif,
      three clusters of highly acidic residues and other structural features found in
      various proteins implicated in chromatin formation. When expressed as a fusion
      protein in Escherichia coli, hNRP reacted specifically with a monoclonal antibody
      raised against human NAP-I. The hNRP transcript was detected in all tissues and
      cell lines studied, but levels were somewhat increased in rapidly proliferating
      cells. Moreover, levels of both hNRP mRNA and protein increased rapidly in
      cultured T-lymphocytes induced to proliferate by incubation with phorbol ester
      and ionomycin. Phorbol 12-myristate 13-acetate/ionomycin-induced increases in
      both hNRP mRNA and mitogenesis, as measured by thymidine incorporation, were
      markedly inhibited, however, in cells treated with an hNRP antisense
      oligonucleotide. These results demonstrate a correlation between induction of
      hNRP expression and mitogenesis and taken together with the structural
      similarities between hNRP and yeast NAP-I suggest that the hNRP gene product
      participates in DNA replication and thereby plays an important role in the
      process of cell proliferation.

PMID- 8297348
TI  - A role for protein kinase C subtypes alpha and epsilon in phorbol-ester-enhanced
      K(+)- and carbachol-evoked noradrenaline release from the human neuroblastoma SH
      SY5Y.
AB  - Protein kinase C (PKC) consists of a family of closely related subtypes which
      differ in their localization and activation properties. Our previous studies have
      suggested a role for PKC in the regulation of noradrenaline (NA) release from the
      human neuroblastoma SH-SY5Y. Here we have used two approaches to characterize the
      PKC subtypes present in SH-SY5Y cells. Firstly, the PCR was used to show that SH
      SY5Y cells contain mRNA encoding PKC subtypes alpha, beta, gamma, delta, epsilon
      and zeta. Secondly, immunoblotting showed that SH-SY5Y cells express PKC subtypes
      alpha, epsilon and zeta at the protein level. Prolonged (48 h) exposure of cells
      to the phorbol ester phorbol 12-myristate 13-acetate (PMA; 100 nM) resulted in a
      marked decrease in the amounts of PKC-alpha and PKC-epsilon, with no change in
      levels of PKC-zeta. Prolonged PMA treatment had no significant effect on K(+)
      evoked NA release from SH-SY5Y cells, whereas carbachol-evoked release was
      increased 2.2-fold. However, prolonged exposure to PMA completely inhibited the
      ability of acute (12 min) PMA treatment to enhance both K(+)- and carbachol
      evoked NA release. The specific PKC inhibitor RO 31-7459 (10 microM) was found to
      inhibit K(+)- and carbachol-evoked release by 27% and 68% respectively. RO 31
      7549 also completely inhibited the ability of acute PMA treatment to enhance
      release. These data suggest that PKC-alpha and/or PKC-epsilon play an essential
      role in the regulation of PMA-enhanced K(+)- and carbachol-evoked NA release in
      SH-SY5Y cells.

PMID- 8297349
TI  - Comparative localization of inositol 1,4,5-trisphosphate and ryanodine receptors
      in intestinal smooth muscle: an analytical subfractionation study.
AB  - [3H]Ins(1,4,5)P3- and [3H]ryanodine-binding sites were characterized in membrane
      fractions from guinea-pig intestinal smooth muscle (longitudinal layer) and their
      subcellular localization was investigated by analytical cell-fractionation
      techniques. Fractions collected at low centrifugal fields (N and M fractions)
      contained predominantly low-affinity [3H]Ins(1,4,5)P3-binding sites (KD 80 nM),
      whereas microsomal (P) fractions contained only high-affinity binding sites (KD 5
      nM). Total sedimentable high-affinity binding sites of [3H]Ins(1,4,5)P3 were 9-10
      fold more numerous than those of [3H]ryanodine. Both high-affinity binding sites
      were purified in microsomal fractions, and their sub-microsomal distribution
      patterns after isopycnic density-gradient centrifugation were similar to those of
      presumed endoplasmic reticulum (ER) constituents, indicating that Ins(1,4,5)P3
      and ryanodine receptors were localized primarily in ER and probably associated
      with rough as well as smooth ER. However, the stoichiometric ratio of
      Ins(1,4,5)P3 to ryanodine receptors was distinctly higher in high-density RNA
      rich subfractions than in low-density RNA-poor subfractions, suggesting that
      Ins(1,4,5)P3 receptors were somewhat concentrated in the ribosome-coated portions
      of ER. The low overall stoichiometric ratio of ryanodine to Ins(1,4,5)P3
      receptors in intestinal smooth muscle (1:9-10) might explain, at least partly,
      the existence of a Ca(2+)-storage compartment devoid of ryanodine-sensitive Ca2+
      channels, but equipped with Ins(1,4,5)P3-sensitive channels, in saponin
      permeabilized smooth-muscle cells [Iino, Kobayashi and Endo (1988) Biochem.
      Biophys. Res. Commun. 152, 417-422].

PMID- 8297350
TI  - The motilin antagonist ANQ-11125 blocks motilide-induced contractions in vitro in
      the rabbit.
AB  - Studies on the physiological role of motilin, and more recently, on the
      relationship between motilin and erythromycin A, have been hampered by the lack
      of antagonists. We now have discovered such a compound. ANQ-11125 displaces
      motilin bound to an homogenate of rabbit antral smooth muscle tissue. The
      dissociation constant (pKd) was 8.16 +/- 0.10. However, ANQ-11125 did not induce
      contractions of segments of rabbit duodenum, except at high concentrations. In
      the presence of 1 microM ANQ-11125 the dose response curves of erythromycin-A,
      De(N-methyl)-N-ethyl-8,9 anhydroerythromycin A 6,9-hemiacetal and motilin were
      shifted about one log unit to the right, but the responses to ACh and Substance P
      were unaffected. Schild-analysis showed the competitive nature of the interaction
      and allowed the calculation of the pA2: 7.03 +/- 0.05 (motilin curves) and 7.55
      +/- 0.06 (EM-523 curves). This is the first report of a motilin antagonist. Its
      properties definitively prove that motilides are motilin agonists.

PMID- 8297351
TI  - Coexistence of folded and extended conformations of a tripeptide containing
      alpha, alpha -di-n-propylglycine in crystals.
AB  - The crystal structure of the tripeptide Boc-Leu-Dpg-Val-OMe (Dpg, alpha, alpha 
      di-n-propylglycine) reveals the coexistence of two distinct backbone
      conformations. In molecule A the Dpg residue adopts a fully extended conformation
      (phi = 76.0 degrees, psi = 180.0 degrees) while in molecule B a left handed
      helical conformation (phi = 62.8 degrees, psi = 39.6 degrees) is observed.
      Molecule B adopts a folded structure corresponding to a highly distorted Type II
      beta-turn conformation, which lacks an intramolecular 4 -> 1 hydrogen bond. In
      contrast, molecule A has an open, extended conformation. The results demonstrate
      that both fully extended and helical conformations are energetically accessible
      to the Dpg residue.

PMID- 8297352
TI  - Primary structure of the large subunit of trifunctional beta-oxidation complex
      from pig heart mitochondria.
AB  - The amino-terminal and internal sequences of the isolated large subunit of
      trifunctional beta-oxidation complex from pig heart mitochondria were determined
      by Edman degradation. The results demonstrated that the sequence of this novel
      beta-oxidation enzyme is identical with the sequence recently reported for a
      porcine gastrin binding protein that serves as the gastrin receptor on parietal
      cell surfaces. Evidence is provided to show that it is unlikely that the porcine
      gastrin binding protein has such a sequence. The data lead us to conclude that
      the mature large subunit of porcine trifunctional beta-oxidation complex is
      composed of 727 amino acid residues with a calculated molecular weight of 79,113,
      while the precursor of this long-chain fatty acid oxidation enzyme has a
      mitochondrial presequence consisting of 36 residues and a calculated M(r) of
      83,099.

PMID- 8297353
TI  - The attenuated elevation of cytoplasmic calcium concentration following the
      uptake of low density lipoprotein in type C Niemann-Pick fibroblasts.
AB  - In Niemann-Pick disease type C fibroblasts, the deficiency of cholesterol
      esterification has been reported. In this experiment, we detected the attenuated
      elevation of cytoplasmic calcium concentration following low density lipoprotein
      uptake in the fibroblasts. Moreover, we administered calcium channel agonist (0.5
      microM YC-170) and calcium channel antagonists to the fibroblasts. YC-170
      improved the attenuated elevation of calcium concentration and the deficient
      cholesterol esterification by 40% and 90% respectively. Calcium channel
      antagonists decreased the cholesterol esterification in normal and affected
      fibroblasts. These data indicated that the attenuated elevation of cytoplasmic
      calcium concentration was strongly related to the etiology of this disease.

PMID- 8297354
TI  - Ion channel activity of a synthetic peptide with a primary structure
      corresponding to the presumed pore-forming region of the voltage dependent
      potassium channel.
AB  - A 26-mer peptide of which the sequence contains the presumed pore forming region
      of the Shaker K+ channel (H5 region) was chemically synthesized. The peptide was
      found to interact and penetrate lipid membranes based on the fluorescence of Trp
      residues of the peptide in the presence and absence of liposomes. The secondary
      structure and the ion channel forming ability of the peptide were measured by CD
      spectroscopy and by a planar bilayer technique, respectively. The secondary
      structure of the peptide was composed of a mixture of an alpha-helix, beta-sheet,
      beta-turn, and a random coil. The content of beta-sheet structure was increased
      by the presence of liposomes. In planar bilayers, the peptide formed anion
      selective ion channels with a larger conductance than that of the native Shaker
      K+ channel. These results suggest that the H5 region of the Shaker K+ channel can
      penetrate into lipid bilayers and form ion channel structures by itself, but it
      requires other structural components to reproduce the native characteristics of
      the K+ channel.

PMID- 8297355
TI  - Dietary deprivation of B-vitamins reflected in murine splenocyte proliferation in
      vitro.
AB  - The effect of murine dietary deprivation of specific B-vitamins on in vitro
      splenocyte proliferative response in short-term tissue culture was examined in
      serum-free, protein-free, minimal medium. Using different media formulations,
      incorporation of [3H]thymidine was used to monitor the relative growth capacity
      of phytohemagglutinin-stimulated splenocytes from mice exposed to different
      diets. The results demonstrate that the growth deficit observed in vitro in the
      absence of specific vitamin(s) in the medium correlates only to those specific
      vitamin(s) eliminated from the diet. Dietary repletion is followed by restoration
      of a normalized response in vitro. The finding that murine dietary experience is
      reflected in vitro in splenocyte proliferative response monitored by
      [3H]thymidine incorporation suggests that human dietary experience might be
      monitored by similar analysis of human peripheral blood lymphocyte response.

PMID- 8297356
TI  - Cyclosporin A sensitive peptidyl-prolyl cis-trans isomerase in a halophilic
      archaeum, Halobacterium cutirubrum.
AB  - A cyclophilin type peptidyl-prolyl cis-trans isomerase was purified from a
      halophilic archaeum, Halobacterium cutirubrum DSM 669. The activity increased
      with an increase in KCl concentration up to 4 M. Sensitivity to cyclosporin A was
      comparable to that of eukaryotic cyclophilin and was also affected by KCl. IC50
      for Cyclosporin A was 1.5 x 10(-8) M in 2.9 M KCl but 1.4 x 10(-7) M in 1.4 M
      KCl. The apparent molecular weight was 31 K by SDS-PAGE and 22 K in 2.9 M KCl and
      150 K in 0 M KCl by gel filtration chromatography. The N-terminal amino acid
      sequence (33 residues) sheared 4 completely and 5 highly conserved amino acid
      residues with other reported cyclophilin family PPIases.

PMID- 8297357
TI  - Molecular basis for developmental changes of GM-CSF gene inducibility in
      embryonal carcinoma cells.
AB  - In a previous report, we reported that the induction of GM-CSF gene in
      differentiated P19 cells results from the maturation of the transcriptional
      machinery. Here, we identified a cis-DNA element which confers the activation of
      GM-CSF gene in response to PMA/A23187 stimulation in differentiated state.
      Analysis of the 5'-flanking region between -113 and -60 revealed two elements
      responsible for promotion and one for inhibition, and the overall effects led to
      the activation of GM-CSF gene mainly through the sequence between -95 and -73.
      Using the oligonucleotide between -94 and -73 as a probe in gel retardation
      assays, we identified a DNA-binding protein, NF-GM-P19, the binding activity of
      which was induced after differentiation in response to PMA/A23187 stimulation.
      These results indicate that the induction of GM-CSF gene after differentiation
      results from the maturation of the transcriptional machinery which recognizes the
      sequence between -95 and -73.

PMID- 8297358
TI  - Induction of pituitary sensitivity to interleukin-1: a new function for
      corticotropin-releasing hormone.
AB  - Activation of the hypothalamic-pituitary-adrenal axis to release corticotropin
      releasing hormone (CRH), corticotropin (ACTH), and glucocorticoids during
      inflammatory stress is now considered a key function of interleukin-1 (IL-1).
      Current dogma suggests that in vivo ACTH release due to IL-1 is indirect and
      entirely results from IL-1-mediated-CRH release from the hypothalamus. The
      present findings show that low levels of exogenous or endogenous CRH can
      sensitize the pituitary gland to the direct ACTH releasing activity of IL-1. Once
      sensitized, IL-1 induced ACTH release is not inhibitable by the CRH antagonist,
      alpha-helical (alpha h) CRF [9-41]. Thus, IL-1 effects ACTH release at the level
      of both the hypothalamus and pituitary gland. Perhaps more importantly, the
      results suggest pituitary sensitization to cytokines, such as IL-1, as a new
      function for CRH. This action would represent a novel interactive point between
      the nervous, endocrine, and immune systems whereby very mild psychological or
      physical stress could have a profound impact on an inflammatory response by
      increasing pituitary sensitivity to immunological mediators such as IL-1.

PMID- 8297359
TI  - Krabbe disease: isolation and characterization of a full-length cDNA for human
      galactocerebrosidase.
AB  - Human galactocerebrosidase, the enzyme deficient in Krabbe disease, was purified,
      through several hydrophobic column steps and gel filtration, 22,650-fold from
      human lymphocytes. Using information on its N-terminal and internal amino acid
      sequences, and the polymerase chain reaction method, we cloned a full-length cDNA
      for the enzyme. The deduced amino acid sequence matched all amino acid sequences
      determined. The 3780 nucleotide sequence included 2007 nucleotides which encoded
      a single chain peptide of 669 amino acid residues with a 26 amino acid N-terminal
      signal peptide and six potential asparagine-linked glycosylation sites. The
      galactocerebrosidase cDNA detected an about 4 kb mRNA band material in human
      cultured skin fibroblasts. A nonsense mutation was found at codon 369 (GAA-->TAA)
      in the coding sequence of cDNA amplified from cultured skin fibroblast mRNA from
      a patient with typical Krabbe disease.

PMID- 8297360
TI  - Tyrosine phosphorylation and activation of mitogen-activated protein kinases by
      thrombin in human platelets: possible involvement in late arachidonic acid
      release.
AB  - Thrombin induced tyrosine phosphorylation of 41-kDa and 43-kDa mitogen-activated
      protein (MAP) kinases in human platelets which was detectable at 1 min and peaked
      at 2 min after thrombin stimulation as assessed by immunoprecipitation and
      immunoblotting. The kinase activity, measured by phosphorylation of myelin basic
      protein, increased concurrently with tyrosine phosphorylation. The present
      results indicate that thrombin activates MAP kinases which may not be involved in
      aggregation and secretory responses but may play a role in the late arachidonic
      acid release via activation of cytosolic phospholipase A2 in human platelets.

PMID- 8297361
TI  - Glial conditioned medium alters the expression of amyloid precursor protein in SH
      SY5Y neuroblastoma cells.
AB  - The effect of conditioned medium from astroglia or microglia cultures on the mRNA
      expression of amyloid precursor protein (APP) in SH-SY5Y human neuroblastoma
      cells was examined. When incubated with conditioned medium of glial cells, SH
      SY5Y cells expressed a larger amount of APP mRNA than the control cells. Reverse
      transcription followed by the polymerase chain reaction showed marked induction
      of expression of APP isoforms containing a Kunitz-type protease inhibitor domain.
      Our results suggest that glial cells may contribute to the regulation of
      expression of APP in neurons.

PMID- 8297362
TI  - Glutathione conjugation with the pyrrolizidine alkaloid, jacobine.
AB  - The reaction of glutathione with the epoxide containing pyrrolizidine alkaloid,
      jacobine, was catalyzed by guinea pig hepatic glutathione-S-transferase enzymes
      in in vitro experiments; the rate of the reaction in the presence of rat hepatic
      glutathione-S-transferases did not differ from the non-enzymatic rate. Using ion
      pairing liquid chromatography we were able to isolate the conjugate and obtain a
      daughter ion spectrum using Fast Atom Bombardment Mass Spectrometry together with
      Collisionally Activated Dissociation/Mass Analyzed Kinetic Energy experiments.

PMID- 8297363
TI  - Inhibition of cell cycle oscillation of DNA replication by a selective inhibitor
      of the cdc2 kinase family, butyrolactone I, in Xenopus egg extracts.
AB  - A selective inhibitor of the cdc2 kinase family, butyrolactone I, was found to
      inhibit the DNA replication activity of Xenopus egg extracts. When metaphase
      arrested Xenopus egg extracts pretreated with butyrolactone I were released into
      interphase by the addition of CaCl2 at low concentrations of sperm nuclei,
      butyrolactone I (10 microM) prevented the oscillation of DNA replication activity
      to a great extent and lengthened the cell cycle. In contrast, in activated
      extracts which had already entered interphase, prepared from eggs activated by
      the calcium ionophore A23187, butyrolactone I (10 microM) had little effect on
      the first peak of the oscillation but reduced to less than half the second peak.
      These inhibitory effects of butyrolactone I on the initiation of DNA replication
      and mitosis in Xenopus egg extracts are probably a consequence of its previously
      reported inhibition of the cyclin-cdc2 kinase family.

PMID- 8297364
TI  - Effects of bile acids and steroid/thyroid hormones on the expression of
      cholesterol 7 alpha-hydroxylase mRNA and the CYP7 gene in HepG2 cells.
AB  - The expression of cholesterol 7 alpha-hydroxylase mRNA levels in confluent HepG2
      cultures was reduced by tauro- or glyco-conjugates of deoxycholate and
      chenodeoxycholate, but not by cholate. Ursodeoxycholates, on the other hand,
      stimulated the mRNA level. The 5'-upstream regions of rat cholesterol 7 alpha
      hydroxylase gene (CYP7) were fused to luciferase reporter gene and the
      constructs, p-3616/Luc, p-224/Luc and p-160/Luc, were transiently transfected
      into HepG2 cells. Tauro-conjugates of deoxycholate and chenodeoxycholate
      inhibited the transcriptional activities of the gene constructs in the confluent
      cells, but not in subconfluent cells. These results reveal that bile acid
      responsive elements are located in the -160 fragment and also between nt -3616
      and -224. Thyroid and steroid hormones stimulated transcriptional activity
      expressed in the confluent cells and their responsive elements are located
      upstream of nt -224. It appears that adult phenotypes are responsible for bile
      acid feedback and hormone response in HepG2 cells.

PMID- 8297365
TI  - Novel fucose-rich glycosaminoglycans from squid ink bearing repeating unit of
      trisaccharide structure (-6GalNAc alpha 1-3GlcA beta 1-3Fuc alpha 1-)n.
AB  - Three fucose-rich glycosaminoglycans (GAGs), illexin A, illexin B and illexin C,
      were isolated from squid ink of Illex argentinus. The GAGs were obtained by the
      method of Actinase E digestion, DEAE Sephadex A-50 ion-exchange chromatography
      and Sephacryl S-300 gel filtration. They gave a single band on the
      electrophoresis using cellulose acetate membrane and contained equimolar ratios
      of Fuc, GlcA and GalNAc. Molecular weights of illexin A, illexin B, and illexin C
      were determined by Sephacryl S-300 gel filtration to be 50,000, 50,000-80,000,
      and 80,000, respectively. These GAGs were not digested with any
      glycosaminoglycanases. On the basis of one and two dimensional NMR spectra,
      glycosidase treatment and periodate oxidation of the pyridylaminated
      trisaccharide obtained by acid hydrolysis of illexin C, the unique repeating
      structure of the GAGs was determined to be (-6GalNAc alpha 1-3GlcA beta 1-3Fuc
      alpha 1-)n.

PMID- 8297366
TI  - Increase of hepatic mRNAS of profilin, actin and extracellular matrix proteins
      after carbon tetrachloride treatment and partial hepatectomy in rats.
AB  - The synthesis of liver collagen increases during the fibrotic process after
      administration of carbon tetrachloride and during regeneration after partial
      hepatectomy in rats. In the present study, we investigated the behavior of
      profilin and actin mRNA under such conditions. Profilin and actin mRNA increased
      after acute and chronic treatments of carbon tetrachloride, which is associated
      with the increase of fibronectin, type-III and -IV collagen mRNA. Furthermore, a
      simultaneous expression of profilin, actin and extracellular matrix proteins was
      observed during the regeneration of rat liver, that is, all mRNAs of these
      proteins showed biphasic peaks around 6 h and 48 h after partial hepatectomy.
      These results suggest that possible coupling might occur between the changes of
      extracellular matrix and the reorganization of actin cytoskeleton in vivo.

PMID- 8297367
TI  - Purification and partial characterization of a heat-resistant, cytosolic
      neuropeptidase from rat liver.
AB  - A cholecystokinin octapeptide (CCK-8)-degrading peptidase was purified from rat
      liver cytosol by heat precipitation of other proteins followed by gel filtration,
      ion exchange chromatography and preparative gel electrophoresis, using a silicate
      binding assay to quantitate the degradation of radiolabeled CCK-8. The purified
      peptidase (M(r) approximately 60,000) had a pH optimum of 6.0; its activity was
      inhibited by EDTA and 1, 10-phenanthroline but not by phosphoramidon, calpain
      inhibitor I, bestatin or bacitracin. CCK-8 peptidase rapidly degraded
      radiolabeled Met-enkephalin as well as 125I-CCK-8, but not a series of other
      unrelated peptides. Unlabeled Leu-enkephalin, beta-casomorphin and neurotensin
      competitively inhibited the degradation of 125I-CCK-8, suggesting that these
      opioids are also substrates for the enzyme. These data suggest that this protein
      is a novel hepatic enzyme which may play a role in the degradation of
      neuropeptides.

PMID- 8297368
TI  - Topoisomerase II-independent doxorubicin-induced cytotoxicity in an extremely
      doxorubicin-resistant cell line.
AB  - Lepidopteran insect cells (TN-368) were found to be extremely resistant to the
      anthracycline, doxorubicin. They were approximately 400 fold more resistant to
      the cytotoxic effects of doxorubicin compared to a mammalian counterpart; V79
      hamster lung fibroblast cells. Doxorubicin accumulated into TN-368 cells and
      bound to DNA in a similar fashion as the interaction of doxorubicin in V79 cells.
      However, no doxorubicin-induced stabilized DNA-topoisomerase II complexes could
      be demonstrated in TN-368 cells (even at the high concentrations of doxorubicin
      that resulted in cytotoxicity). Therefore, the lack of formation of this critical
      lesion may be the cause of the marked doxorubicin resistance noted in the TN-368
      cells.

PMID- 8297369
TI  - Cell type and stimulus specific regulation of chemokine gene expression.
AB  - The pattern of chemoattractant cytokine gene (IP-10, JE, KC) expression has been
      examined in BALB/c 3T3 fibroblasts and MC3T3-E1 osteoblasts in response to a
      variety of different inflammatory stimuli, including IFN gamma, TNF alpha, IL-1
      alpha, and IL-6. Both cell types expressed JE and IP-10 mRNAs but the response
      pattern varied in a stimulus- and gene-dependent fashion. KC mRNA was only
      expressed in BALB/c 3T3 cells stimulated by IL-1 alpha. The time dependence for
      expression was distinctive for each gene but was comparable despite different
      forms of stimulation. Nevertheless, the mechanisms involved in the induction of
      each gene varied with the stimulus and involved both transcriptional and post
      transcriptional components. These findings reflect the diversity of chemokine
      gene expression in vivo and may be important in mechanistic understanding of the
      diversity of inflammatory response patterns.

PMID- 8297370
TI  - Gene organization and 5'-flanking region sequence of conglutinin: a C-type
      mammalian lectin containing a collagen-like domain.
AB  - Bovine conglutinin is a Ca(2+)-dependent serum lectin specific for N
      acetylglucosamine. In the present study, we report the exon-intron organization
      and the sequence of 5'-regulatory region of the conglutinin gene. The coding
      region of conglutinin mRNA, which encoded the signal peptide and the sequence of
      the mature protein of 351 amino acids, consisted of seven exons. Exon III encoded
      the signal peptide, a cysteine-rich NH2-terminal region and six repeats of a Gly
      X-Y triplet with one irregular triplet. The remaining long collagen-like domain
      (49 Gly-X-Y repeats with one irregular triplet) was encoded by four separate
      exons (Exon IV-VII). Exon VIII encoded the neck region and Exon IX encoded the
      carbohydrate-recognition domain. The overall exon-intron organization of
      conglutinin was very similar to that of mannan (mannose)-binding proteins.
      However, the presence of 108 bp exons in the gene encoding the collagen-like
      domain was a characteristic of conglutinin. In the promoter region of the gene,
      several putative consensus sequences that may be involved in the expression of
      conglutinin were identified.

PMID- 8297371
TI  - Chemical synthesis and structure-function studies of margatoxin, a potent
      inhibitor of voltage-dependent potassium channel in human T lymphocytes.
AB  - The 39 amino acid peptide, margatoxin (MgTX), a potent inhibitor of the voltage
      activated potassium channel (Kv 1.3) in human T lymphocytes, was synthesized by a
      solid phase technique. Formation of the disulfide bridges was rapid at pH 8.2.
      The final product was purified to homogeneity and was physically and biologically
      indistinguishable from the toxin prepared biosynthetically. The disulfide bridge
      pairing was similar to that found previously for the related toxin-charybdotoxin
      (3): from Cys7 to Cys29, from tested for inhibition of 125I margatoxin binding to
      voltage-activated potassium channels. The results indicate that the three C
      terminal residues of MgTX are important for the efficient toxin binding to Kv1.3.

PMID- 8297372
TI  - Functional coupling of human adenosine receptors to a ligand-dependent reporter
      gene system.
AB  - We have stably transfected CHO cells that have integrated in their genome a
      reporter gene under the control of promoter sequences containing several copies
      of the cAMP response element, CRE, with different human adenosine receptors: A1,
      A2a and A2b. The new cell lines responded to the addition of known adenosine
      agonists and antagonists with changes in the expression of the reporter gene. The
      activity of the reporter gene can be easily monitored by bioluminescence.
      Although adenosine receptors are divergently coupled to adenylate cyclase, A1
      receptors inhibit whereas A2 stimulate, changes in gene expression faithfully
      reflected the negative and positive coupling of the receptors. We have used the
      system to examine the pharmacological profile of the human receptors expressed in
      CHO cells.

PMID- 8297373
TI  - Identification of a nonsense mutation in ALD protein cDNA from a patient with
      adrenoleukodystrophy.
AB  - The molecular basis of X-linked adrenoleukodystrophy (ALD) was investigated. Six
      (A to 50) fragments of cDNA for ALD protein (Mosser et al. Nature 361: 726-730,
      1993) from an adult patient with adrenomyeloneuropathy were amplified by PCR and
      mutations were screened by Mutation Detection Enhancement gel electrophoresis. A
      single base substitution (2154 C-->T, which resulted in the formation of a
      termination codon for glutamine (Q590STOP) and deletes Pst I site (CTGCAG-
      >CTGTAG), was detected. Eight other ALD patients did not have this mutation. A
      family study revealed the presence of both the mutant and normal alleles in the
      mother, a sister and a niece, indicating that these individuals were carriers. A
      nephew with childhood ALD who died 10 years earlier had the same mutant allele as
      detected by Pst I restriction assay. This report is the first description of a
      mutant allele for ALD, at the cDNA level, and presents confirmatory evidence of
      ALD protein as the primary etiology of ALD.

PMID- 8297374
TI  - The putative rat choline transporter CHOT1 transports creatine and is highly
      expressed in neural and muscle-rich tissues.
AB  - A rabbit homolog of the putative rat choline transporter CHOT1 has recently been
      shown to mediate creatine transport (Guimbal and Kilimann, J. Biol. Chem., 1993).
      Here, the functional properties of the CHOT1 cDNA were studied by heterologous
      expression in HEK-293 cells. After transfection, the cells displayed a 7-8fold
      stimulation of [14C]creatine uptake with a Km of 46.2 microM. This transport was
      inhibited by the creatine uptake inhibitor beta-guanidinopropionate (Ki of 23
      microM). Northern blot analysis revealed a major transcript of 4.8 kb in brain,
      heart, skeletal muscle and kidney. In situ hybridization showed high transcript
      levels in the cerebellum, hippocampus and other brain regions. High expression
      was also seen in the rat embryo along the entire neuraxis and in some non
      neuronal tissues. These data establish CHOT1 as a widely expressed rat creatine
      transporter.

PMID- 8297375
TI  - Structure-function relationship in the serotransferrin: the role of the pH on the
      conformational change and the metal ions release.
AB  - We report experimental evidence that the pH value of the micro-environment of the
      protein is the key for the conformational changes of transferrin, rather than the
      ligated for unligated state of the binding sites. The "open" and "closed"
      conformation of protein, suggested by X-ray crystallography in static condition,
      is triggered by the pH value and the effect is independent of the metal ion being
      transported. We propose a simple description of the structure-function
      relationship that allows this protein to deliver, in particular, iron or aluminum
      ions in the biological cycle.

PMID- 8297376
TI  - CCAAT/enhancer binding proteins alpha and beta are transcriptional activators of
      the brown fat uncoupling protein gene promoter.
AB  - Primary brown adipocytes differentiated in culture were transiently transfected
      with plasmids containing different extensions of the 5'-flanking region of the
      rat uncoupling protein gene placed upstream of the bacterial chloramphenicol
      acetyltransferase reporter gene. Co-transfection of expression vectors for
      CCAAT/enhancer binding protein (C/EBP) alpha and C/EBP beta trans-activated the
      rat uncoupling protein gene promoter due to sequences in the 5' proximal region.
      DNAse I footprint analysis showed the presence of two C/EBP binding sites at
      positions -457/-440 and -335/-318, which interact with purified C/EBP beta as
      well as with C/EBP proteins present in brown fat or liver nuclear extracts. Two
      copies of each site placed upstream of the enhancerless SV40 promoter confer
      C/EBP alpha and C/EBP beta responsiveness to this heterologous promoter when co
      transfected into HepG2 cells. It is concluded that the UCP gene is a target for
      C/EBP-dependent transcriptional regulation. This suggests that the C/EBP family
      of transcription factors is involved in the establishment of the characteristic
      phenotype of the brown adipocyte.

PMID- 8297377
TI  - Oligomeric casein kinase II isoforms are expressed in bovine tissues and
      adrenocortical cells in culture.
AB  - Casein kinase II is a ubiquitous serine-threonine kinase made of two different
      (alpha and beta) subunits, with an alpha 2 beta 2 stoichiometry, alpha bearing
      the catalytic site of the enzyme. Two different genes encode two different (alpha
      and alpha') catalytic subunits. The present work shows that at least two forms of
      CKII (CKIIa and CKIIb) can be isolated from bovine tissues and adrenocortical
      cells in culture. The use of specific antibodies developed against the alpha and
      alpha' subunits disclosed that while CKIIa contains both alpha and alpha', the
      alpha subunit was highly prominent in CKIIb. This suggests that CKIIb may be an
      alpha 2 beta 2 oligomer whereas CKIIa may be an alpha alpha' beta 2 moiety or an
      alpha alpha' beta 2 and alpha' 2 beta 2 mixture. Transition from quiescence to
      proliferation was concomitant with an average two fold increase in total cell
      CKII activity involving both CKIIa and CKIIb isoforms. The two isoforms were
      found in cytosolic and particulate adrenocortical subcellular preparations and
      they similarly increased their association to intracellular organelles in
      response to growth stimulatory conditions.

PMID- 8297378
TI  - X-ray crystal structure of cross-linked subtilisin Carlsberg in water vs.
      acetonitrile.
AB  - The crystal structure of subtilisin Carlsberg lightly cross-linked with
      glutaraldehyde was solved in aqueous solution by X-ray crystallography at 2.3 A
      resolution. It was found to be virtually identical to the recently determined
      (Fitzpatrick, P.A., Steinmetz, A.C.U., Ringe, D.A. & Klibanov, A.M. (1993) Proc.
      Natl. Acad. Sci. USA 90, 8653) structure of the cross-linked enzyme in anhydrous
      acetonitrile. The latter structure was found to be significantly more rigid than
      in water, as reflected by their average B factors. The numbers of subtilisin
      bound water molecules in the two structures are similar (114 and 99 in water and
      in acetonitrile, respectively), but the locations of some half of these bound
      waters are distinct.

PMID- 8297379
TI  - The exon-intron structure and chromosomal localization of the mouse macrophage
      mannose receptor gene Mrc1: identification of a Ricin-like domain at the N
      terminus of the receptor.
AB  - The macrophage mannose receptor is a transmembrane protein that is expressed on
      the surface of mature macrophages. The ectodomain of the receptor contains
      multiple domains, eight of which belong to the calcium-dependent C-type lectin
      family. The mannose receptor binds to carbohydrate polymers that have a high
      content of mannose. This property allows this protein to function as a phagocytic
      receptor that participates in first-line host defense against invading
      microorganisms. In this paper we describe the intron-exon structure of the mouse
      macrophage mannose receptor gene which was found to span at least 70 kilobases.
      We also report the localization of this gene, termed Mrc1, to mouse Chromosome 2.
      Like its human counterpart, Mrc1 contains 30 exons and 29 introns. A protein
      module that resembles a subdomain of the B chain of the plant lectin Ricin has
      been found within the N-terminal cysteine-rich domain of the mannose receptor.

PMID- 8297380
TI  - Localization of osteogenic protein-1 (bone morphogenetic protein-7) during human
      embryonic development: high affinity binding to basement membranes.
AB  - Osteogenic protein-1 (OP-1) is a member of the bone morphogenetic protein
      subfamily of the transforming growth factor-beta (TGF-beta) superfamily. Since
      members of the TGF-beta superfamily have a role in tissue development the
      distribution of OP-1 in developing human embryos (gestational age 5-14 weeks) was
      examined by immunohistochemical methods. Positive staining for OP-1 was observed
      in: sclerotome, hypertrophied chondrocytes, osteoblasts, periosteum, epithelial
      cells of the adrenal "provisional cortex" and the convoluted tubules of
      developing kidneys. In the developing lungs, pancreas and skin, OP-1 was
      localized in basement membranes underlying the epithelium. In vitro binding
      studies of 125I-OP-1 to various extracellular matrix components revealed high
      affinity of OP-1 for type IV collagen and less for heparin, collagen types I and
      VI. Present findings suggest that, in addition to bone formation, OP-1 could have
      other important regulatory roles in human embryogenesis with high binding
      affinity to a basement membrane component.

PMID- 8297381
TI  - The ryanodine receptor from canine heart sarcoplasmic reticulum is associated
      with a novel FK-506 binding protein.
AB  - We find that the purified ryanodine receptor/calcium release channel (CRC)
      isolated from canine heart sarcoplasmic reticulum (SR) is tightly associated with
      an FK-506 binding protein which is distinct from human recombinant FKBP-12.
      Fractions from both skeletal and heart muscle were probed by Western Blot
      analysis using sequence specific antibody raised against the N-terminus of human
      recombinant FKBP-12. Only FKBP-12 was detected in rabbit and dog skeletal muscle
      SR as well as in dog heart cytosol. Canine heart SR and the purified canine heart
      ryanodine receptor contained an immunoreactive band with a somewhat slower
      relative mobility than that of human recombinant FKBP-12. These observations
      indicate that the association between the cardiac CRC and this novel FK-506
      binding protein is specific.

PMID- 8297382
TI  - Identification of a new adult human liver sulfotransferase with specificity for
      endogenous and xenobiotic estrogens.
AB  - We present evidence for the existence of a previously undescribed
      sulfotransferase isoenzyme in adult human liver which sulfates endogenous and
      xenobiotic estrogens (estrone and 17 alpha-ethinylestradiol). The enzyme was
      resolved from other sulfotransferases using anion exchange chromatography and
      further purified by gel filtration and affinity chromatography. Using antibodies
      against rat liver estrogen and hydroxysteroid sulfotransferases, it was shown
      that the adult human estrogen sulfotransferase has a subunit molecular weight of
      33kDa, is immunologically related to its rat counterpart and also to the human
      phenolsulfotransferase enzyme family, but not to human hydroxysteroid
      sulfotransferase.

PMID- 8297383
TI  - Aromatic stacking and bending of the DNA helix by the individual repeat units of
      the carboxy-terminal domain of RNA polymerase II.
AB  - The carboxy-terminal domain (CTD) of RNA polymerase II consists of multiple
      repeats of the unique heptad sequence -(Ser-Pro-Thr-Ser-Pro-Ser-Tyr)- which may
      interact with DNA through the intercalation of adjacent tyrosine aromatic rings.
      We have examined details of the interaction of this motif with calf thymus DNA
      through analysis of peptide analogues that contain (1) an amino-terminal tyrosine
      which mimics the presence of an adjacent heptad repeat and (2) positively-charged
      lysine residues which facilitate the initial contact between peptide and DNA.
      Results of fluorescence experiments, NMR titrations, and viscometric analyses
      indicate that these peptides bind to the DNA helix through a non-classical
      intercalation mode involving partial aromatic stacking of the tyrosine rings with
      the Watson-Crick base pairs.

PMID- 8297384
TI  - Erythroid differentiation-inducing activity of protoporphyrin IX and its analogs
      on human leukemia K562 cell line.
AB  - Protoporphyrin IX, which had been regarded as ineffective in cell
      differentiation, induced erythroid differentiation of K562 cell line, and its
      analogs such as hematoporphyrin IX, mesoporphyrin IX, deuteroporphyrin IX and
      protoporphyrin IX dimethyl ester were also differentiation inducers. The
      differentiation induced by these compounds was augmented by a retinoid, as is
      hemin-induced differentiation.

PMID- 8297385
TI  - Caffeine inhibits agonists-induced cytoplasmic Ca2+ oscillations in single rat
      hepatocytes.
AB  - Single hepatocytes microinjected with aequorin generate free Ca oscillations when
      stimulated by agonists such as phenylephrine or vasopressin. Here we show that
      caffeine by itself does not elicit any significant change in free Ca, nor it does
      lower the threshold concentration of an agonist needed to induced spikes. In
      contrast, both caffeine and theophylline inhibit agonist-induced spikes. Since
      ryanodine inhibits vasopressin-induced spikes, but not phenylephrine-induced
      spikes, the actions of caffeine probably involve another target than the
      ryanodine receptor. This antagonistic action of caffeine on the hepatocyte
      calcium oscillator agrees with an inhibitory action of caffeine on the receptor
      for inositol 1,4,5-triphosphate.

PMID- 8297386
TI  - The Drosophila melanogaster homolog of ribosomal protein L27a.
AB  - The amino acid sequence of the Drosophila melanogaster 60S ribosomal sub-unit
      protein, L27a, was deduced from the sequence of nucleotides in a recombinant
      cDNA. Ribosomal protein L27a has 149 amino acids with a molecular weight of
      17,123 Daltons. Hybridisation of the cDNA to polytene chromosomes indicates the
      presence of a single gene on chromosome 3R at 87F/88A. There is a single mRNA for
      the protein of around 650 nucleotides in length. Drosophila ribosomal protein
      L27a is homologous to the rat and yeast L27a and to the other members of the L15
      ribosomal protein family. There is also significant homology with an invertebrate
      motor protein and a Drosophila photoreceptor morphogenesis protein.

PMID- 8297387
TI  - Molecular cloning and DNA sequence of rat amelogenin and a comparative analysis
      of mammalian amelogenin protein sequence divergence.
AB  - The developing rat incisor is a common model used in the study of enamel
      development. It has been impossible to study correlation between rat enamel
      structure and the sequence of the major developing enamel protein in this species
      as to date a DNA sequence for rat amelogenin has not been reported. This study
      presents the first cloning of a full-length cDNA copy of rat amelogenin and its
      deduced primary sequence. Detailed analysis of this sequence provides evidence
      that the gene has evolved by internal sequence duplication. Comparison of the rat
      amelogenin primary sequence with those published for other species provides
      evidence that this protein, while exhibiting extreme levels of sequence
      conservation, has been subject to significant structural changes that may be
      related to alterations in enamel structure in different mammalian groups.

PMID- 8297388
TI  - Fenofibric acid modulates the human apolipoprotein A-IV gene expression in HepG2
      cells.
AB  - The influence of the hypolipidemic drug, fenofibric acid, on the regulation of
      apolipoprotein A-IV (apoA-IV) gene expression was investigated in two human cell
      lines, HepG2 and Caco-2. As shown in the present report, fenofibric acid induces
      a strong dose-dependent increase of the apoA-IV mRNA level in HepG2 cells, while
      other apolipoproteins mRNA levels are only slightly modified. In Caco-2 cells, no
      modification is observed, except for a 2-fold increase of the apoE mRNA level.
      The increase of the apoA-IV mRNA level could be correlated with a clear
      enhancement of DNase I hypersensitive sites in the 5' flanking region of the gene
      in nuclei of HepG2 cells treated with fenofibric acid. Thus, fenofibric acid may
      act by facilitating the interaction of nuclear regulatory proteins with the DNA
      in the control regions of the apoA-IV gene.

PMID- 8297389
TI  - UV induction of excision repair enzymes detected in protein extracts from
      Schizosaccharomyces pombe.
AB  - Induction of genes and proteins after DNA damaging treatment is well documented
      in various biological systems. In order to monitor repair activity in
      Schizosacchromyces pombe, we adapted the biochemical assay that allowed specific
      quantification of excision repair in mammalian cells (Wood et al. 1988, Cell, 53,
      97-106) to yeast-free extracts. Repair synthesis determined on UV-damaged plasmid
      DNA with S. pombe total protein extract relied on base excision repair and not
      nucleotide excision repair. Under conditions that allowed optimal repair
      activity, an enhanced repair synthesis was found with extract from yeast
      previously irradiated with UV light (254 nm). A 4-fold induction factor was
      obtained with 70 J/m2 irradiation dose after 40 min incubation post-irradiation.
      This base excision repair activity on UV photoproducts was transiently induced
      since it returned to the level of untreated yeast after about 2 hours post
      irradiation.

PMID- 8297391
TI  - Proteolytic processing of farnesylated peptides: assay and partial purification
      from pig brain membranes of an endopeptidase which has the characteristics of
      E.C. 3.4.24.15.
AB  - The proteolytic processing of farnesylated peptides was investigated with the
      tritiated C-terminal heptapeptide of mouse N-Ras protein, Propionyl-Gly-Ser-Pro
      (farnesyl-Cys)-[3H]Val-Leu-Met, as substrate. Using two rapid and sensitive
      methods, the peptidase which cleaves the (farnesyl-Cys)-[3H]Val bond was purified
      more than 100 times from a microsomal fraction of pig brain. The determination of
      its molecular mass (about 70 kDa) and its pH range for optimum activity (neutral
      pH) as well as the results obtained with various inhibitors indicate that this
      [3H]Val-Leu-Met releasing enzyme resembles endopeptidase 24.15: a thiol-dependent
      zinc metallopeptidase. Parallel and comparative inhibition assays on partially
      purified enzyme and pure "24.15" confirm this similarity.

PMID- 8297390
TI  - Differential subcellular localisation of two isoforms of p70 S6 protein kinase.
AB  - Ribosomal protein S6 phosphorylation is stimulated by a variety of hormones and
      growth factors. In mammalian cells the predominant S6 kinase is a 70 kDa enzyme
      which exists in two forms differing only in their amino terminal region. To
      determine whether this difference is functionally significant we have examined
      the intracellular localisation of the two forms. In cells transfected with cDNA
      encoding the longer alpha I p70 S6 kinase, protein is found in both the
      cytoplasmic and nuclear compartments. In contrast, the shorter alpha II
      polypeptide is confined to the cytoplasm. The significance of this differential
      localisation is discussed with respect to the recent identification of p70 S6
      kinase activity as being essential for cell-cycle progression and thus
      mitogenesis.

PMID- 8297392
TI  - New cytochrome P450-dependent reactions from wheat: terminal and sub-terminal
      hydroxylation of oleic acid by microsomes from naphthalic acid anhydride and
      phenobarbital induced wheat seedlings.
AB  - Incubation of the microsomal fraction from etiolated wheat shoots (Triticum
      aestivum L. cv Etoile de Choisy) with [1-14C]oleic acid led to the formation of
      three polar metabolites which were identified as 18-, 17- and 16-hydroxyoleic
      acids by gas chromatography/mass spectra analysis. They were generated in a molar
      ratio of 1.4/4.6/4, respectively. Terminal and sub-terminal hydroxylation of
      oleic acid and the cytochrome P450 content were strongly enhanced in microsomes
      from wheat shoots treated with naphthalic acid anhydride and phenobarbital. The
      involvement of cytochrome P450 is demonstrated by the dependence of hydroxylation
      upon O2 and NADPH, and by their light-reversible inhibition by carbon monoxide.
      In addition, the hydroxylation of oleic acid, but not of lauric acid and cinnamic
      acid, was inhibited when microsomes where incubated with 9-octadecen-16-ynoic
      acid, a substrate analogue displaying an acetylenic function at the carbon
      position of major enzyme attack. Our results suggest that at least two different
      P450 enzymes are involved in the oxidation of oleic and lauric acids in wheat.

PMID- 8297393
TI  - The Dbl oncogene product as a GDP/GTP exchange protein for the Rho family: its
      properties in comparison with those of Smg GDS.
AB  - The dbl oncogene product (Dbl) showed the GDP/GTP exchange protein (GEP) activity
      on all the rho family small GTP-binding protein (G protein) members including
      RhoA and Rac1 as well as mCdc42. Dbl was active on both the lipid-modified and 
      unmodified forms of these small G proteins, but was much more active on the
      former form than on the latter form. In the presence of Rho GDI, an inhibitory
      GEP for the rho family members, the GEP activity of Dbl was markedly reduced.
      These properties of Dbl were partly different from those of Smg GDS, another GEP
      which is active not only on the rho family members but also on Ki-Ras and Rap1
      and is active only on their lipid-modified form.

PMID- 8297394
TI  - In vitro cytogenetic effects of 2450 MHz waves on human peripheral blood
      lymphocytes.
AB  - Cytogenetic analyses were performed on human peripheral blood lymphocytes exposed
      to 2450 MHz microwaves during 30 and 120 min at a constant temperature of 36.1
      degrees C (body temperature). The temperature was kept constant by means of a
      temperature probe put in the blood sample which gives feedback to a microcomputer
      that controls the microwave supply. We found a marked increase in the frequency
      of chromosome aberrations (including dicentric chromosomes and acentric
      fragments) and micronuclei. On the other hand the microwave exposure did not
      influence the cell kinetics nor the sister chromatid exchange (SCE) frequency.

PMID- 8297395
TI  - The effect of pulsed microwaves on passive electrical properties and interspike
      intervals of snail neurons.
AB  - The effects of pulsed microwaves (2.45 GHz, 10 microseconds, 100 pps, SAR: 81.5
      kW/kg peak, 81.5 W/kg average) on membrane input resistance and action potential
      (AP) interval statistics were studied in spontaneously active ganglion neurons of
      land snails (Helix aspersa), at strictly constant temperature (20.8 +/- .07
      degrees C worst case). Statistical comparison with sham-irradiated neurons
      revealed a significant increase in the mean input resistance of neurons exposed
      to pulsed microwaves (P < or = .05). Pulsed microwaves had no visible effect on
      mean AP firing rate; this observation was confirmed by analysis of interspike
      intervals (ISIs). Using an integrator model for spontaneously active neurons, we
      found the net input current to be more variable in neurons exposed to pulsed
      microwaves. The mean input current was not affected. The standard deviation of
      ISIs and the autocorrelation of the input current were marginally affected, but
      these changes were not consistent across neurons. Although the observed effects
      were less obvious than those reported in other studies, they represent evidence
      of a direct interaction between neurons and pulsed microwaves, in the absence of
      macroscopic temperature changes. The data do not suggest a single, specific
      mechanism for such interaction.

PMID- 8297396
TI  - Calcium-ion movement and contractility in atrial strips of frog heart are not
      affected by low-frequency-modulated, 1 GHz electromagnetic radiation.
AB  - Calcium efflux from electrically stimulated, 45Ca(2+)-preloaded atrial strips of
      the frog heart was measured from samples of the rinsing perfusate collected at 2
      min intervals for 32 min in a continuous perfusion chamber. Contractile force was
      simultaneously monitored. The specimen chamber was located in a stripline
      apparatus in which the atrial strips were exposed for 32 min to constant (CW) or
      amplitude-modulated (AM), 1 GHz electromagnetic (EM) fields at specific
      absorption rates (SAR) ranging from 3.2 microW/kg to 1.6 W/kg. Amplitude
      modulation was either at 0.5 Hz, in synchrony with the electrical stimulus
      applied to the preparation, or at 16 Hz. Neither unmodulated nor 0.5 Hz or 16 Hz
      modulated 1 GHz waves affected the movement of calcium ions or the contractile
      force in isolated atrial strips of the frog heart.

PMID- 8297397
TI  - Facility for chronic exposure of rats to ELF magnetic fields.
AB  - The facility consists of a 12 x 11.5 x 2.4 m high room containing six sets of
      exposure apparatus and the other equipment necessary to maintain a pathogen-free
      system. The apparatus sets produced 5 mT (rms), 0.5 mT, or a sham exposure. The
      apparatus was arranged in the room to minimize the fringing field of the 5 mT set
      at the sham position. Each set was 3.85 x 1.80 x 0.66 m in outside dimension,
      containing 24 cages in the magnetically homogeneous region. The apparatus was
      designed using Harvey's figure-eight-configuration and generated a horizontal
      sinusoidal alternating field. In order to save electric power, the coil of the
      apparatus constituted a 50 Hz LC resonance circuit with a condensor bank to which
      electric power was supplied to compensate losses. Magnetic flux density was kept
      constant by controlling the coil current. Although mild steel was used in the
      skeleton of the building, the fringing flux at the sham was as low as 0.1 to 1
      microT. Stainless steel was used for ventilating ducts, racks for the cages, cage
      covers, feeder baskets, and watering nozzles. The homogeneity of the field was
      measured to be +/- 10% in the animal residence area, and food and water
      consumption was found to be unaffected by the field. At 5 mT, the coil current
      was 370 A, and the hollow coil was cooled by a stream of 20 degrees C water to
      prevent both heat and dew on the coil surface. Vibration and acoustic noise was
      prevented by fiber reinforced plastic framework of the coil. High harmonic
      distortion was not observed at the output terminal of the coil driver. The
      facility has operated without trouble for 2 years.

PMID- 8297398
TI  - Synergistic effects of ionizing radiation and 60 Hz magnetic fields.
AB  - Experiments designed to evaluate the synergistic production of clastogenic
      effects by ionizing radiation and 60 Hz magnetic fields were performed using
      human lymphocytes from peripheral blood. Following exposure to ionizing
      radiation, cells were cultured in 60 Hz magnetic fields having field strengths up
      to 1.4 mT. Cells exposed to both ionizing radiation and 60 Hz magnetic fields
      demonstrated an enhanced frequency of near tetraploid chromosome complements, a
      feature not observed following exposure to only ionizing radiation. The results
      are discussed in the context of a multiple-stage model of cellular
      transformation, employing both initiating and promoting agents.

PMID- 8297399
TI  - Pain control using high-intensity pulsed magnetic stimulation.
AB  - High-intensity pulsed magnetic stimulation (HIPMS) non-invasively depolarizes
      neurones, which can be deeply embedded in local tissues. Trans- or subcutaneous
      electrical stimulation can produce analgesia. To test the hypothesis that similar
      analgesia could be obtained using HIPMS, analgesia was determined in ten blinded
      subjects following HIPMS. Analgesia was consistently produced in all subjects
      with long-lasting pain relief occurring in half of the cases.

PMID- 8297400
TI  - The mystery of cerebral venous hemoglobin desaturation during rewarming: what is
      "the solution?".

PMID- 8297401
TI  - Cardiodynamic effects of propofol in comparison to thiopental. Use of the end
      systolic pressure-volume relationship and arterial elastance.

PMID- 8297402
TI  - Amyloid, amyloid-inducers, cytokines and heavy metals in scrapie and other human
      and animal subacute spongiform encephalopathies: some hypotheses.
AB  - A number of hypotheses regarding the pathogenesis of scrapie and other human and
      animal spontaneous and experimental subacute spongiform encephalopathies (SSE)
      are presented here. In particular, it is speculated that a PrPsc 27-30-induced
      suppression of host's defense system is responsible, through the existence of the
      different and synergistically operating mechanisms, for the absence of any
      documented inflammatory or immunologic response during SSE. This could be
      therapeutically counterparted by the utilization of cytokines (TNF, IL-1, etc) or
      cytokine-inducers, provided that synthesis and secretion of the above
      inflammation mediators on behalf of reticulo-endothelial cells were strongly
      depressed by PrP 27-30, as suggested. Finally, some hypotheses are also made in
      relation to the blood-brain-barrier's integrity in susceptible hosts. Similarly
      to Alzheimer's disease (AD) in man, this could play a role also in SSE
      pathogenesis, facilitating cerebral localization of metals such as aluminum,
      lead, or silica, which have already been shown to enhance amyloid fibrils'
      polymerization and deposition within human brain tissue.

PMID- 8297403
TI  - IV steroid treatment of giant cell arteritis.

PMID- 8297404
TI  - Alternative allergy and the GMC.

PMID- 8297405
TI  - Self monitoring of blood glucose.

PMID- 8297406
TI  - Tomlinson report.

PMID- 8297407
TI  - Chiropractic.

PMID- 8297408
TI  - Self-referral by physicians.

PMID- 8297409
TI  - Increased costs and rates of use in the California workers' compensation system
      as a result of self-referral by physicians.

PMID- 8297410
TI  - Honing clinical skills.

PMID- 8297411
TI  - The science and policy of risk.

PMID- 8297412
TI  - Mitochondrial DNA mutations associated with age.

PMID- 8297413
TI  - Drugs and dilators for achalasia.

PMID- 8297414
TI  - Initial experience with single lead VDD system. Case study.
AB  - A single pass lead with dual chamber electrode system, designed for atrial and
      ventricular sensing and ventricular pacing (VDD), was implanted in a 63-year-old
      man with a history of syncope and second degree atrioventricular (AV) block.
      Intact VDD pacing function was confirmed at rest and during treadmill exercise.
      There were no postoperative complications. A single pass lead system that allows
      VDD mode pacing in patients with symptomatic AV block and competent sinus node
      function offers several advantages over traditional two lead dual chamber
      systems. These advantages include enhanced atrial sensing due to a differentially
      processed signal reliable for P wave detection and effective for rejection of far
      field ventricular signals, lowered cost and reduced implant time.

PMID- 8297415
TI  - Analysis of myocardial oedema by magnetic resonance imaging early after coronary
      artery occlusion with or without reperfusion.
AB  - OBJECTIVE: The aim was to analyse the relationship between magnetic resonance
      (MR) imaging parameters and myocardial water content early after coronary
      occlusion with or without reperfusion. METHODS: 21 pigs were used. After 78 min
      of coronary occlusion (n = 7) or 48 min of coronary occlusion and 30 min of
      reperfusion (n = 14) the heart was excised. In seven animals in the reperfusion
      protocol the area at risk was perfused for 5 min with an anoxic buffer, starting
      5 min after coronary occlusion. Serial T2 weighted and density weighted images of
      the heart were obtained from apex to base, by using a 1.5 tesla magnetic
      resonance imager. Water content was measured in samples from control and at-risk
      myocardium and relaxation parameters were measured in corresponding areas of the
      magnetic resonance images. RESULTS: Water content was 399(SEM 2) ml x 100 g-1 dry
      tissue in control myocardium, 427(8) in ischaemic myocardium, and 511(8) in
      reperfused myocardium (p < 0.001). Reperfused myocardium that had received
      intracoronary infusion contained less water than myocardium that did not: 498(9)
      v 534(4) ml x 100 g-1 (p = 0.003). T2 relaxation time and T2 weighted signal
      intensity in the different sampling sites of magnetic resonance images correlated
      well with water content in the corresponding myocardial samples (r = 0.76 and r =
      0.83) and with the relative volume of extracellular space, as calculated by
      quantitative histology (r = 0.58 and r = 0.59, p < 0.001). The increase in T2
      weighted signal intensity in the area at risk with respect to control myocardium
      allowed differentiation between ischaemic and reperfused myocardium [9(8)% v
      63(3)% respectively]. The area at risk measured by MR imaging correlated very
      well with that determined at pathology by the fluorescein method (r = 0.92).
      CONCLUSIONS: Magnetic resonance imaging allows evaluation of myocardial oedema
      associated with acute coronary occlusion and reperfusion, and analysis of its
      spatial distribution. Changes in myocardial water content occurring early during
      acute myocardial infarction allow quantification of the area at risk and
      detection of reperfusion by magnetic resonance imaging.

PMID- 8297416
TI  - HCFA, NIH taking a closer look at vascular access.

PMID- 8297417
TI  - Protein kinase C as an early and sensitive marker of ischemia-induced progressive
      neuronal damage in gerbil hippocampus.
AB  - In the model of transient brain ischemia of 6-min duration in gerbils we have
      estimated: 1. The concentration of brain gangliosides: A significant decrease to
      about 70% of control was observed selectively in the hippocampus at 3 and 7 d
      after ischemia. 2. The activity of Na+,K(+)-ATPase: The enzyme activity was not
      affected in either hippocampus nor in cerebral cortex. 3. The malonaldehyde (MDA)
      concentration: The levels of MDA had increased at 30 min after ischemia up to 123
      and 129% of control in hippocampus and cerebral cortex, respectively. 4.
      Immunoreactivity of protein kinase C detected by Western blotting: In hippocampus
      the early translocation toward membranes was followed by a decrease in total
      enzyme content at 6, 24, 72, and 96 h of postischemic recovery. Also, a sharp
      increase of 50 kDa isoform (PKM) was noticed immediately and at the early
      recovery times. The behavior of these biochemical markers of ischemic brain
      injury in the hippocampus after the short (6 min) insult was contrasted with
      their reaction in the cerebral cortex as well as after prolongation of the
      ischemia to 15 min. These results taken together indicate that an early increase
      in PKC translocation followed by a decrease is the most symptomatic for
      selective, delayed, postischemic hippocampal injury, resulting from short
      duration (6 min) ischemia of the gerbil brain.

PMID- 8297418
TI  - Phorbol ester-induced neuritic alterations in the rat neocortex. Structural and
      immunocytochemical studies.
AB  - In order to explore the effect of aberrant sprouting in the CNS, phorbol 12
      myristate 13-acetate (PMA) was administered into the neocortex of adult rats. PMA
      is a growth-promoting agent that activates and eventually downregulates protein
      kinase C (PKC), and induces in the rat the expression of several genes, including
      amyloid precursor protein (APP). We found that multiple injections of 100 nM PMA
      into the rat neocortex promote, in the first week postinjection, a widespread
      vacuolization of the neuropil with a subsequent disruption of the synapses in the
      injection site, followed, at d 15, by the formation of abnormally distended
      clusters of neurites that resembled aberrant, sprouting axons. At d 30, fewer
      aberrant sprouts were observed, and many degenerating neurites were found. At the
      ultrastructural level, the PMA-induced abnormal neurites at d 7-15 resembled
      growth cones, whereas the dystrophic neurites at d 30 contained abundant dense
      and laminated bodies. Immunohistochemical analysis indicated that the abnormal
      neurites in the areas of denervation and PMA administration were positive with
      antisynaptophysin and antigrowth-associated protein 43 (GAP-43), with an
      increased APP immunoreactivity surrounding them. APP immunoreactivity around the
      injection site was mostly associated with pyramidal neurons and glial cells.
      Control experiments, where saline alone or 4 alpha-phorbol 12, 13-didecanoate
      (PDD, an inactive phorbol derivative) was injected, failed to show aberrant
      sprouting neurites. Further immunohistochemical analysis showed that the PMA
      treated animals presented increased amyloid beta immunoreactivity in the
      pyramidal cells at the site of injection, when compared with control injections.
      These findings suggest that aberrant sprouting induced by overstimulation could
      be followed by neurodegeneration. Alternatively, PKC downregulation could
      directly induce the neurodegeneration, with a secondary sprouting response.

PMID- 8297419
TI  - The use of salicylate hydroxylation to detect hydroxyl radical generation in
      ischemic and traumatic brain injury. Reversal by tirilazad mesylate (U-74006F).
AB  - Oxygen free radicals have been implicated as a causal factor in posttraumatic
      neuronal cell loss following cerebral ischemia and head injury. The conversion of
      salicylate to dihydroxybenzoic acid (DHBA) in vivo was employed to study the
      formation of hydroxyl radical (.OH) following central nervous system (CNS)
      injury. Bilateral carotid occlusion (BCO) in gerbils and concussive head trauma
      in mice were selected as models of brain injury. The lipid peroxidation
      inhibitor, tirilazad mesylate (U-74006F), was tested for its ability to attenuate
      hydroxyl radical formation in these models. In addition, U-74006F was studied as
      a scavenger of hydroxyl radical in an in vitro assay based on the Fenton
      reaction. For in vivo experimentation, hydroxyl radical formation was expressed
      as the ratio of DHBA to salicylate (DHBA/SAL) measured in brain. In the BCO
      model, hydroxyl radical formation increased in whole brain with 10 min of
      occlusion followed by 1 min of reperfusion. DHBA/SAL was also found to increase
      in the mouse head injury model at 1 h postinjury. In both models, U-74006F (1 or
      10 mg/kg) blocked the increase in DHBA/SAL following injury. In vitro, reaction
      of U-74006F with hydroxyl radical gave a product with a mol wt that was 16
      greater than U-74006F, indicative of hydroxyl radical scavenging. We speculate
      that U-74006F may function by blocking oxyradical-dependent cell damage, and
      thereby maintaining free iron (which catalyzes hydroxyl radical formation)
      concentrations at normal levels.

PMID- 8297420
TI  - The influence of ImuVert, a biological response modifier, on the growth and
      ganglioside composition of murine neural tumors.
AB  - ImuVert is a biological response modifier (BRM) that has antitumor effects in
      humans and rats. The influence of ImuVert on the ganglioside composition of two
      experimental brain tumors, ependymoblastoma and CT-2A, was studied in C57BL/6J
      mice. Gangliosides are expressed on plasma membranes and can serve as markers to
      distinguish neural cells from nonneural cells in mouse brain tumors. N
      acetylneuraminic (NeuAc) is the predominant sialic acid in mouse neural cells,
      whereas N-glycolylneuraminic (NeuGc) is a major sialic acid in nonneural cells,
      e.g., macrophages and lymphocytes. ImuVert treatment increased the NeuGc
      ganglioside concentration in the ependymoblastoma, but had no effect on the
      sialic acid concentration in the CT-2A brain tumor. ImuVert also had a slight
      inhibitory effect on the growth of both brain tumors.

PMID- 8297421
TI  - Effect of hyperbaric oxygen on prostaglandin and thromboxane synthesis in the
      cortex and the striatum of rat brain.
AB  - The effect of a previous exposure to hyperbaric oxygen (HBO) on the synthesis
      capacity of prostaglandin (PG) and thromboxane (TX) was investigated in the brain
      of male rats. Three groups of rats were used: 1. Neurotoxic HBO (n = 11): The
      rats were exposed to sixfold the atmospheric pressure (101.3 kPa), i.e., 6
      absolute atmospheres (ATA), of pure O2 up to the first convulsion (6 ATA O2); 2.
      Mild hyperoxia (n = 10): The rats were exposed to compressed air at the same
      absolute pressure and for a similar time than that of the neurotoxic HBO group
      (here PO2 is 1.26 ATA); 3. Normoxia at atmospheric pressure (PO2 is 0.21 ATA) for
      control. There was no convulsion in groups 2 and 3. Decompression of the high
      pressure groups lasted 15 min. After decapitation, samples of the frontal cortex
      and the striatum were taken, weighed, washed, and then incubated in Krebs-Ringer
      bicarbonate for 1 h. The release of eicosanoids in the medium was determined by
      enzyme immunoassay. Mild hyperoxia only significantly reduced in the striatum the
      release of 6-keto-PGF1 alpha (1.3 +/- 2.4 vs 10.9 +/- 6.6 pg/mg wet tissue, p <
      0.001; mean +/- SD) and PGE2 (3.2 +/- 2.7 vs 7.8 +/- 6.5 pg/mg wet tissue, p <
      0.05), whereas TXB2 did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297422
TI  - Biochemical activities of propolis extracts. I. Standardization and antioxidative
      properties of ethanolic and aqueous derivatives.
AB  - Ethanolic extracts of Propolis are used as antiinflammatory and wound healing
      drugs since ancient times. In order to facilitate a comparison of different
      extracts, the standardization on the basis of quantitative determination of
      prominent components of these extracts has been substituted for simple
      biochemical "activity" tests. One of these activity tests bases on the inhibition
      of peroxidase-catalyzed oxidation of indole acetic acid indicating the presence
      of a defined mixture of monophenolic and diphenolic compounds. Other tests
      (diaphorase-catalyzed reductions and xanthine oxidase-catalyzed oxidations)
      demonstrate significant radical scavenging properties. Water-soluble extracts of
      propolis exhibit higher antioxidative and inhibitory activities as compared to
      the ethanolic extract.

PMID- 8297423
TI  - Biochemical activities of propolis extracts. II. Photodynamic activities.
AB  - Ethanolic and aqueous extracts of the "bee glue" Propolis exhibit antioxidative
      properties and are used as antiinflammatory drugs in folk medicine. In order to
      standardize the principle activities of prominent components of these extracts,
      simple biochemical tests have been introduced in the preceding paper. These
      activity tests prove the high antioxidative and inhibitory capacities of aqueous
      and ethanolic extracts of propolis in vitro. In the present communication we
      report on experiments documenting photodynamic quenching properties of these
      extracts. Using riboflavin, rose bengal or hematoporphyrin as photoactivators and
      ketomethylthiobutyric acid or crocin as indicators, the protective functions of
      propolis preparations can be demonstrated. The results indicate that the aqueous
      extracts are more active than the corresponding ethanolic preparation.

PMID- 8297424
TI  - Diurnal fluctuations of cocaine and potential precursors in leaves of
      Erythroxylum coca.
AB  - Cocaine is abundant in leaves of Erythroxylum coca var. coca Lam. Consequently,
      cocaine and two of its early biosynthetic precursors were monitored for 24 h to
      determine whether they fluctuated diurnally. E. coca was grown under controlled
      environmental conditions in a growth chamber in soil at pH 3.5. After 17.5 months
      of growth, leaves not less than 35 days old were harvested every 2 and 4 h for 24
      h for arginine, phenylalanine and cocaine content, respectively. The content of
      cocaine was determined by GC/MS and amino acid content by HPLC. Diurnal
      fluctuation of cocaine occurred during the 24 h cycle. Cocaine was highest in
      leaves of E. coca at 8 and 16 h where its content was 7.67 and 9.45 mg.g-1 dry
      weight, respectively. Arginine and phenylalanine in leaves of E. coca also
      displayed diurnal rhythmic patterns of fluctuation. The content of arginine
      declined from hours 6 to 12 and increased to the highest content at 13 h (21.8
      mg.g-1 dry weight). Overall, phenylalanine content was lower than arginine, but
      had two peak periods of accumulation during the 24 h cycle, occurring at 8 and 14
      h. The content of phenylalanine in leaves of E. coca during the peak hours was
      6.98 and 6.54 mg.g-1 dry weight, respectively.

PMID- 8297425
TI  - X-ray studies on phospholipid bilayers. XIV. Interactions with the antiarrhythmic
      asocainol.
AB  - Asocainol (ASOC) belongs to class I of the antiarrhythmic drugs, i.e., those that
      exert their action at the level of the sodium channels of the myocardial cell
      membrane. It has been suggested that their molecular mechanism of action might be
      through nonspecific interactions with phospholipids that surround the channel
      proteins. In order to test this hypothesis, ASOC was made to interact with two
      multibilayer systems, one built-up of dimyristoylphosphatidylcholine (DMPC) and
      the other of dimyristoylphosphatidylethanolamine (DMPE). These are the type of
      lipids that are respectively found in the outer and inner monolayers of human
      erythrocytes. The experiments were carried out in a hydrophobic as well as in a
      hydrophilic medium below the phospholipid main transition temperatures. The
      perturbing effect of ASOC upon the bilayer structures was determined by X-ray
      diffraction. It was found that ASOC was able to fluidize DMPC in both media but
      not to DMPE.

PMID- 8297426
TI  - Antibiotic and cytotoxic activity of brominated compounds from the marine sponge
      Verongia aerophoba.
AB  - Analysis of the marine sponge Verongia aerophoba from the Canary Islands afforded
      eight brominated secondary metabolites including the small molecular weight
      compounds aeroplysinin-1 (5) and the dienone (7) which were previously shown to
      arise by enzymatically catalyzed degradation of aerophobin-2 (4) and
      isofistularin-3 (1) following breakdown of the cellular compartmentation of the
      sponge. All compounds were identified from their NMR and mass spectra.
      Aeroplysinin-1 as well as dienone which arise from isofistularin-3 or aerophobin
      2 by biotransformation within the sponge showed a significantly higher antibiotic
      as well as cytotoxic activity than their biogenetic precursors. Antibiotic
      activity was studied with respect to several gram-positive and gram-negative
      bacteria including B. subtilis, S. aureus and E. coli. The MICs (MBCs) of
      aeroplysinin-1 (5) and the dienone (7) varied between 12.5-25 (50-100)
      micrograms/ml respectively. Cytotoxicity was tested in vitro towards HeLa cells,
      a human cervix uteri tumour cell line. Aeroplysinin-1 (5) and the dienone (7)
      displayed pronounced cytotoxic activity with IC50s of 3.0 and 3.2 microM
      respectively. A five-fold increase in cytotoxicity was observed after O
      acetylation of the dienone (7). The IC50 of the dienone O-acetate (0.6 microM)
      was comparable to that of the clinically used anticancer drug cisplatin (0.7
      microM).

PMID- 8297427
TI  - Malignancy-associated changes in monocytes and lymphocytes in acute leukemias
      measured by high-resolution image processing.
AB  - A number of methods are available for classifying lymphoid and myeloid leukemias
      in peripheral blood and bone marrow. However, in clinical diagnosis an initial
      and particularly important step is morphologic analysis. All the cells in this
      investigation were classified by two hematologic experts. In most cases,
      immunophenotyping and immunocytochemical analyses were performed. Routinely
      prepared Romanowsky-Giemsa-stained peripheral blood smears (approximately 23,000
      cells) were scanned by a high-resolution color TV/microscope system and analyzed
      by color and texture algorithms. In addition to blast cells, lymphocytes and
      monocytes exhibited a leukemia-associated change in morphology. The calculated
      texture and color features were most significant for the subtyping performed by
      the statistical program. With multivariate statistical analysis, seven
      mathematical subtypes of lymphocytes and five of monocytes could be found over
      all the specimens. Acute myeloblastic leukemia (AML, M1-M2), acute myelomonocytic
      leukemia (AMMOL, M4) and acute monocytic leukemia (AMOL, M5) could be
      differentiated by their distributions of monocyte subtypes. However, this was
      impossible for the lymphocyte subtypes. Acute lymphoblastic leukemias (B-ALL and
      T-ALL) were discernible with the aid of lymphocyte subtypes and acute myeloid
      conditions from viral infections, such as with the Epstein-Barr virus. The method
      increased the relevance of image processing in clinical diagnosis of acute
      leukemias and showed that the "normal" cell populations were not really normal in
      malignant leukemias.

PMID- 8297428
TI  - Quantitative measurement of hemosiderin deposition in tissue sections of the
      liver by image analysis.
AB  - Hemosiderin has been quantitated in tissue sections by image analysis employing
      Perls' Berlin blue reaction. A linear correlation was observed between the mean
      optical density of the tissue section measured with a commercial image analyzer
      and the iron concentration measured with an atomic absorption spectrophotometer.
      The correlation coefficient of .945 (P < .001) indicated that a linear
      correlation existed between these measurements. Thus, the hemosiderin volume in
      tissue sections can be measured quantitatively by image analysis.

PMID- 8297429
TI  - Nuclear DNA content and clinical follow-up in resected pancreatic adenocarcinoma.
AB  - Nuclear DNA content was determined by image analysis of paraffin-embedded tissue
      sections in 20 cases of resected pancreatic ductal adenocarcinoma. Seven cases
      (35%) showed a diploid pattern; 13 (65%) were aneuploid. Mean survival time of
      patients with diploid tumors was significantly greater (17 months) than for
      patients with aneuploid carcinomas, 7.5 months (P < .03, Kaplan-Meier and Cox
      univariate analysis). Patient age, grade of differentiation, primary tumor size
      and lymph node status did not correlate significantly with ploidy pattern and
      survival. In four cases atypical hyperplasia/adenocarcinoma in situ was present
      in the main duct epithelium at the pancreatectomy resection line. These
      intraductal foci were uniformly diploid. We conclude that despite the uniform
      fatality of pancreatic cancer, adenocarcinomas with aneuploid patterns pursue a
      significantly more rapid and aggressive clinical course than do diploid tumors
      and that the atypical intraductal epithelial foci that may accompany resected
      specimens from invasive adenocarcinoma are DNA diploid, may represent noninvasive
      precursor lesions and are of uncertain clinical significance.

PMID- 8297430
TI  - Breast cytology diagnosis with digital image analysis.
AB  - An interactive computer system has been developed for evaluating cytologic
      features derived directly from a digital scan of breast fine needle aspirate
      slides. The system uses computer vision techniques to analyze cell nuclei and
      classifies them using an inductive method based on linear programming. A digital
      scan of selected areas of the aspirate slide is done by a trained observer, while
      the analysis of the digitized image is done by an untrained observer. When
      trained and tested on 119 breast fine needle aspirates (68 benign and 51
      malignant) using leave-one-out testing, 90% correctness was achieved. These
      results indicate that the method is accurate (good intraobserver and
      interobserver reproducibility) and that an untrained operator can obtain
      diagnostic results comparable to those achieved visually by experienced
      observers.

PMID- 8297431
TI  - Automated three-dimensional image analysis of thick and overlapped clusters in
      cytologic preparations. Application to cytologic smears.
AB  - Methods are presented for automated analysis of thick and heavily overlapped
      regions of cytologic preparations, such as cervical/vaginal smears. Current
      systems are unable to process these regions although they contain diagnostically
      valuable information. We argue that analysis of such regions is inherently a
      three-dimensional (3-D) problem that cannot be solved reliably with conventional
      two-dimensional methods. Furthermore, this issue cannot be side-stepped by
      special thin preparation methods. Even with 3-D imaging, analysis of these
      regions is complicated by the high variability in the image gray level and
      textural features resulting from the uncontrollable cell overlaps and folds and
      large computational requirements. A novel approach based on 3-D imaging and
      adaptive 3-D analysis algorithms based on the principles of localization,
      adaptive data reduction and clustering theory is presented. It was successful in
      detecting and separating deeply embedded and overlapping nuclei, cytoplasmic
      folds and creases in thick and overlapped regions of conventional smears and
      special thin preparations.

PMID- 8297432
TI  - Comparison of image analysis and flow cytometric measurements of DNA content of
      canine transitional cell carcinomas.
AB  - The DNA content of neoplasms is generally determined by flow cytometry, but
      quantitative microscopic image analysis is an alternative technique for DNA
      quantification. To compare these two methods, the DNA content of 31 paraffin
      embedded canine transitional cell carcinomas was measured by flow cytometry and
      image analysis. Interpretable data were available for 26 samples by flow
      cytometry and 27 samples by image analysis. For 23 neoplasms with interpretable
      data by both methods, a good correlation (r = .80, P < .001) was obtained between
      the DNA indices determined by flow cytometry and image analysis. Concordance of
      DNA ploidy classification was reached in 21 samples; however, for 4 samples an
      aneuploid cell population, usually tetraploid, was identified by image analysis
      and not by flow cytometry. Two samples also had aneuploid peaks by flow cytometry
      and not by image analysis. Although a good correlation was seen between the
      measurement of DNA content of paraffin-embedded canine tissue by image analysis
      and flow cytometry, this study did demonstrate that aneuploid cell populations
      can be missed by both methods and that image analysis was better than flow
      cytometry in the detection of aneuploid cell populations, particularly tetraploid
      ones, in samples with excessive cellular debris.

PMID- 8297433
TI  - Road safety rhetoric versus road safety politics.
AB  - In-depth interviews with top level decision makers in the road sector in Norway
      were conducted over a four-year period: Three principal impediments to safety
      interventions were identified: (i) Mobility is considered of primary importance;
      the "freedom of the car" is difficult to restrict, (ii) as a consequence there is
      much more lobbying for mobility than for safety, and (iii) road safety commitment
      and policies are weak, even among some of those responsible. For these reasons,
      efficient road safety work is often side-tracked at the top level, and
      substituted by nonbinding demands for road users' "change of attitude". In
      addition, road safety is often used as a proxy argument for measures that mainly
      promote mobility.

PMID- 8297434
TI  - The construction of a road injury database.
AB  - In order to effectively examine possible causes and determinants of road trauma,
      reliable information on the participants, circumstances, and resultant injuries
      and deaths must be available. Characteristics of participants (persons and
      vehicles) and the circumstances of road accidents are routinely collected by
      police and road authorities, whereas details of the injuries and medical care
      provided to casualties are collected by hospital and ambulance services. A road
      injury database, linking data collected by the Health, Police, and Main Roads
      Departments of the Government of Western Australia with records of the St. John
      Ambulance Association and the Death Register, has been established. This paper
      describes the procedures used to link the various sources of data and discusses
      the design, construction, and quality of the resultant relational database.

PMID- 8297435
TI  - Tiredness and visual reaction time among nighttime cab drivers: a roadside
      survey.
AB  - The present roadside survey seeks to elucidate the incidence of tiredness among
      nighttime cab drivers by comparing self-assessed level of tiredness with the
      results of a simple visual reaction test. Attempts to separate various forms of
      fatigue from sleepiness are not made, as it appears less important in studies of
      everyday traffic than in experimental investigations. One-hundred-and-twenty cab
      drivers of vacant cabs were stopped by the police on a major highway just outside
      the city of Copenhagen. Eighty drivers declared themselves rested, 38 tired, and
      2 very tired. The reaction test showed considerable individual variation, but
      subdivision of the drivers according to level of tiredness demonstrated a
      statistically significant and uniform difference throughout the night (p <
      0.0001). One self-assessed tired driver was reclassified to the group of very
      tired based on the questionnaire and reaction test. The investigation indicates
      that accidents due to "driver asleep" would be expected among the three (2.5%)
      very tired cab drivers. The questionnaire and visual reaction test turned out to
      be complementary in the present study and are both useful implements for future
      roadside surveys of tiredness in nighttime traffic.

PMID- 8297436
TI  - Development of a new injury cost scale.
AB  - The Automobile Technique Research Association at Frankfurt, the Institute for
      Forensic Medicine at Mainz, the Federal Highway Research Institute at Bergisch
      Gladbach, the German Motor Vehicle Inspection Association at Stuttgart, and the
      German Worker's Compensation at St. Augustin have completed a joint research
      project dealing with injury costs due to automobile accidents. The data for this
      social cost analysis were based on costs for administrative expenses, medical
      treatment, rehabilitation measures, social security payment, and loss of income,
      which were all paid by Worker's Compensation for single, well-documented injuries
      to the working population in West Germany (15 to 65 years old). The data base
      used included 15,407 injured and 1,026 fatal road accident victims. Tables are
      presented which show the costs associated with various injury levels. The result
      is an injury cost scale (ICS) that might be a base for establishing priorities of
      safety measures. The ICS has to be seen as supplemental to the AIS.

PMID- 8297437
TI  - Modeling vehicle accidents and highway geometric design relationships.
AB  - The statistical properties of four regression models--two conventional linear
      regression models and two Poisson regression models--are investigated in terms of
      their ability to model vehicle accidents and highway geometric design
      relationships. Potential limitations of these models pertaining to their
      underlying distributional assumptions, estimation procedures, functional form of
      accident rate, and sensitivity to short road sections, are identified. Important
      issues, such as the treatment of vehicle exposure and traffic conditions, and
      data uncertainties due to sampling and nonsampling errors, are also discussed.
      Roadway and truck accident data from the Highway Safety Information System
      (HSIS), a highway safety data base administered by the Federal Highway
      Administration (FHWA), have been employed to illustrate the use and the
      limitations of these models. It is demonstrated that the conventional linear
      regression models lack the distributional property to describe adequately random,
      discrete, nonnegative, and typically sporadic vehicle accident events on the
      road. As a result, these models are not appropriate to make probabilistic
      statements about vehicle accidents, and the test statistics derived from these
      models are questionable. The Poisson regression models, on the other hand,
      possess most of the desirable statistical properties in developing the
      relationships. However, if the vehicle accident data are found to be
      significantly overdispersed relative to its mean, then using the Poisson
      regression models may overstate or understate the likelihood of vehicle accidents
      on the road. More general probability distributions may have to be considered.

PMID- 8297439
TI  - Field investigations of the performance of air bag deployments in frontal
      collisions.
AB  - This paper documents field investigations of "air bag" crashes selected from a
      large group of air bag crashes in file at the University of Michigan
      Transportation Research Institute (UMTRI). A full range of crashes are presented
      with injury levels of AIS 1-2 to AIS 5-6. Most occupants sustained minor
      injuries. Those not wearing the lap-shoulder belt (3-point belt) had more minor
      injuries than the restrained. The occurrence of higher level injuries (AIS > or =
      2) was found more often in the nonbelted.

PMID- 8297438
TI  - Alcohol use, driving records, and crash culpability among injured motorcycle
      drivers.
AB  - Alcohol use, driving records, crash culpability, and crash conviction rates for
      165 injured motorcycle drivers (MTCDs) were studied. Of the 165 MTCDs, 53.3%
      tested positive for alcohol (BAC+). Culpability determinations (n = 150) revealed
      that 83% of BAC+ and 46% of BAC-MTCDs caused their crashes (p < 0.001). Driving
      records (n = 145) revealed the following prevalence of one or more convictions
      for BAC+ and BAC-MTCDs: impaired driving (29% vs. 7%, p < 0.001); speeding (74%
      vs. 58%, p < 0.05); and reckless driving (68% vs. 44%, p < 0.002). Of the
      surviving culpable impaired MCTDs (n = 48), 16.7% received crash-related
      convictions, 12.5% received alcohol-related convictions. The reasons for the low
      conviction rates are probably multifactorial.

PMID- 8297440
TI  - A review of cervical fractures and fracture-dislocations without head impacts
      sustained by restrained occupants.
AB  - Crash injury reduction via lap-shoulder belt use has been well documented. Like
      any other interior car component, lap-shoulder belts may be related to injury in
      certain crashes. Relatively unknown is the fact that cervical fractures or
      fracture-dislocations to restrained front seat occupants occur where no head
      contact was evidenced by both medical records and car inspection. A review of the
      available literature on car crash injuries revealed more than 100 such cases. A
      review of the National Accident Severity Study (NASS) 80-88 file was also
      conducted, revealing more examples. Case capsule descriptions from the authors'
      files are also detailed along with examples of such injuries in infants and
      children in child restraints. However, cervical fractures or fracture
      dislocations are rare, as evidenced by the relatively few cases identified in the
      literature, in the author's files, and by an analysis of NASS 80-90 data that
      revealed a cervical spine injury frequency of only .4% at the AIS-3 level
      (Huelke, Morris, and Mackay 1992).

PMID- 8297441
TI  - Demographic and socioeconomic correlates of safety belt use.
AB  - This study analyzed the relationship between safety belt use rates--as measured
      by observational surveys at preselected sites--and demographic and socioeconomic
      characteristics--as reflected by the U.S. Census Bureau data for the sites. The
      results showed consistent and moderately high associations between observed
      safety belt use rates and socioeconomic status indicators, primarily home value.
      Once redundancies among variables were removed, other variables that contributed
      significantly to explaining differences between high- and low-belt use sites were
      the percentage of elderly people (55+ years old) and the mix of blue and white
      collar workers. Sites having high safety belt use rates had higher average home
      values, a higher percentage of elderly people, and a lower percentage of blue
      collar workers than sites having low use rates. Simple correlations with belt use
      rates were also obtained for race, marital status, presence of children in
      household, education, and income.

PMID- 8297442
TI  - Seat belt use and accident involvement: a comparison of driving behavior before
      and after a seat belt law.
AB  - In an earlier study, researchers at the University of North Carolina Highway
      Safety Research Center found drivers classified as seat belt nonusers on the
      basis of direct observation and self-reported belt use to be overrepresented in
      prior accidents and violations. This study represents a follow-up and extension
      of the earlier study where accident and violation rates over a 2.5-year interval
      following the classification by seat belt use status are compared. Seat belt
      nonusers were again found to be overrepresented in both accidents and violations.
      In other analyses of these data, changes in seat belt use status were found not
      to be associated with changes in accident or violation rates, and seat belt use
      rates reported by police in accidents following the mandatory seat belt law
      greatly exceeded both the observed and self-reported use rates. This was
      especially pronounced for drivers who responded that they rarely or never used
      seat belts.

PMID- 8297443
TI  - The expected loss of life quality from traffic injuries requiring
      hospitalisation.
AB  - Assuming a probability distribution of the loss of life quality for each level of
      impairment, this paper estimates a range for the expected loss of life quality
      caused by serious (requiring hospitalisation) nonfatal traffic injuries. The
      results obtained are close to those determined independently in the United
      Kingdom.

PMID- 8297444
TI  - Falls from moving motor vehicles in New Zealand.
AB  - Injuries due to falls from moving motor vehicles have received relatively little
      attention from the research community. Injury events of this type in New Zealand
      were examined using national injury mortality and hospitalisation data from the
      New Zealand National Health Statistics Centre (NHSC). Also used were data
      obtained from the New Zealand Post Motor Registration Centre and from coroner's
      investigation reports held by the Department of Justice. Fifty-six fatal falls
      from moving motor vehicles occurred during the period 1977-1986 (0.18 per 100,000
      population per year). The average age of fatalities was 23. The total potential
      years of life lost due to these fatalities was 2,696, or an average of 48 years
      per person. Thirty-nine persons (70%) fell while riding on the exterior of a
      vehicle. None of the 56 fatalities was using a belt restraint when he/she fell.
      Four hundred and twenty-three admissions to hospital occurred during 1986 and
      1987 (6.5 per 100,000 persons per year). The average age of those hospitalised
      was 18. Incidence rates were highest in the 0-4, 15-19, and 20-24 year age
      groups. In the case of both deaths and hospitalisations, the incidence rate for
      males was approximately double the rate for females. In addition, the rate of
      falls (per unit registered motor vehicle) from trucks was significantly higher
      than the rate of falls from cars. Means of preventing falls from motor vehicles
      are discussed.

PMID- 8297445
TI  - Prevalence of alcohol-impaired driving: an international comparison.
AB  - This paper reports international differences in the extent of alcohol-impaired
      driving. These differences are then interpreted in the light of inducements and
      disincentives to drink and to drive.

PMID- 8297446
TI  - [A profound stress reaction during epidural opiate analgesia in combination with
      weak neuroleptanalgesia in comparison with neuroleptanesthesia Type II alone].
AB  - The modifying influence of anaesthetic procedures on stress reaction linked to
      operating trauma was observed by measurement of plasma concentration of beta
      endorphin. In a prospective study 54 patients undergoing a radical gynaecological
      operation were allocated to either neuroleptanaesthesia type II or epidural
      morphine analgesia combined with slight neuroleptanaesthesia. The observation
      period was extended from the first preoperative day to the first postoperative
      day and included 11 measurements. The plasma concentration of beta-endorphin was
      determined by radioimmunoassay technique. At the beginning of the operation both
      groups of patients showed a significant increase in the plasma concentration of
      beta-endorphin, with the peak value occurring at the end of the operation. The
      patients undergoing epidural morphine analgesia in combination with slight
      neuroleptanaesthesia reached about five times higher levels of plasma
      concentration of beta-endorphin than the patients receiving neuroleptanaesthesia
      type II. The results show that the systemic administration of opiates suppresses
      the excessive activation of neuroendocrine stress systems to a greater extent
      than epidural administration. These results may be explained by the assumed worse
      quality of antinociception by epidural administration of morphine. This is
      thought to be caused by the late administration of the drug, by the non-selective
      occupation of the spinal opioid receptors and by the inadequate activation of the
      diffuse descending inhibitory control systems. The role of supraspinal mechanisms
      involved in opiate analgesia is discussed.

PMID- 8297447
TI  - [Endocrine and hemodynamic effects of naloxone following modified
      neuroleptanesthesia].
AB  - This study was undertaken to investigate the influence of the opiate-antagonist
      naloxone on the endocrine stress response and haemodynamic parameters after
      modified neuroleptanaesthesia in a randomized, prospective design. A total number
      of 22 patients (ASA-scores I or II) between 18 and 60 years scheduled for major
      gynaecologic surgery were included. For modified neuroleptanaesthesia, midazolam,
      fentanyl and vecuronium were administered in standardized doses. After
      extubation, patients of the naloxone-group received injections of 2 x 0.1 mg
      naloxone; in controls, no naloxone was used. Endocrine stress parameters and
      haemodynamic parameters were measured 7 times before induction of anaesthesia and
      up to 60 minutes after the operation. In both groups, remarkable increases in
      adrenaline, noradrenaline, antidiuretic hormone, adrenocorticotropic hormone,
      cortisol, glucose and lactate took place in the postoperative period. This stress
      response was comparable in both groups and not increased by naloxone. No
      significant influence of naloxone on mean arterial pressure, heart rate and
      arterial oxygen saturation was observed. After neuroleptanaesthesia, a careful
      opiate antagonism with small doses of naloxone is not disadvantageous with
      respect to endocrine stress response and haemodynamic reactions.

PMID- 8297448
TI  - [Potassium substitution during coronary surgery: K(+)-Mg+(+)-aspartate-complex
      (Inzolen) versus potassium chloride].
AB  - Potassium loss may cause arrhythmias and cardiac injury in patients undergoing
      heart surgery with cardiopulmonary bypass (CPB). In a prospective, randomized
      trial two different methods of potassium substitution were investigated regarding
      their influence on cardiac rhythm following reperfusion. Patients received either
      potassium chloride (Group I, n = 102) or potassium magnesium aspartate (Inzolen,
      group II, n = 105) to achieve intraoperative serum potassium concentrations of
      4.5 mmol/l. St. Thomas cardioplegic solution was used. CPB was performed in
      moderate hypothermia (28-32 degrees C) with a non-pulsatile pump flow, a membrane
      oxygenator and a single two-stage venous catheter. The two study groups were
      comparable with regard to biometric data, preoperative state, duration of
      operation, ischemia and clinical outcome. In 6 patients in group I and in 3
      patients in group II perioperative myocardial infarction was diagnosed based on
      ECG and CK-MB findings. One patient in each group died during the postoperative
      hospital stay. At the time of declamping mean serum potassium concentration was
      4.9 +/- 0.7 mmol/l in group I and 4.8 +/- 0.5 mmol/l in group II (n.s.). The
      concentration of magnesium was significantly lower in the potassium chloride
      substitution group (1.48 mmol/l) compared to the other group (2.33 mmol/l) (p <
      0.05). No significant differences in cardiac electric activity were observed
      between the two groups. The incidence of ventricular fibrillation in the early
      reperfusion period was 37% versus 45% (n. s.). In both groups patients with a
      potassium value of < 4.5 mmol/l showed a significantly higher incidence of
      ventricular fibrillation. Five percent of the patients had bradycardia requiring
      temporary pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297449
TI  - [Selective gut decontamination in ventilated intensive therapy patients].
AB  - Treatment of long-term artificially ventilated patients is often complicated by
      nosocomial infections. The infection that occurs with the highest frequency
      during intensive care treatment is pneumonia (22-63%). Ninety per cent of
      nosocomial infections of intensive care patients are endogenous infections caused
      by mainly gram-negative aerobic microorganisms that have colonized in the
      gastrointestinal tract. Selective decontamination of the intestine provides a
      method that prevents nosocomial infections. In a prospective study 13 patients
      whose oropharynx and gastrointestinal tract had been decontaminated (SDD) were
      compared to 17 patients in a control group. In a third group twelve patients were
      decontaminated in the gastrointestinal tract (SGD) only, and in a fourth group 16
      patients were decontaminated in the oropharynx (SMD) only. Trachea, oropharynx
      and faeces of the patients belonging to the control group (KG) were colonized to
      almost 100% with gram-negative bacteria. Only 10% of the patients of the SDD and
      SMD groups showed gram-negative bacteria located in the trachea and oropharynx
      after one week of decontamination. No gram-negative aerobic bacteria were present
      after seven days in the faeces of the patients of the SDD and SGD groups. There
      was no difference with regard to the trachea and oropharynx between the control
      group and the SGD group. The gram-negative aerobic intestinal flora was not
      affected by the selective mouth decontamination. The average rate of pneumonia
      occurrence within the 15-day observation period was 28.2% for the control group,
      14% for the SGD group, and 9.6% for the SDD group, and 4.1% for the SMD group.
      Decontamination of the oropharynx of patients is essential in order to
      successfully prevent pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297450
TI  - Perspectives in dental health care.

PMID- 8297451
TI  - A long-term prospective study of the etched-cast restoration.
AB  - The etched-cast restoration was introduced in 1980, and a prospective study was
      initiated in March 1981 to determine if resin-bonded prostheses would prove to be
      a long-term alternative to traditional complete and partial coverage
      restorations. All resin-bonded restorations placed since that time in the
      author's private prosthodontic practice have been recorded in the study. The
      success rate of 127 restorations has been 92.9%, with a mean longevity of 5 years
      and 8 months.

PMID- 8297452
TI  - Torque required to loosen single-tooth implant abutment screws before and after
      simulated function.
AB  - The amount of torque required to loosen screws from three different
      antirotational screw-retained abutment/implant combinations was compared (with
      and without adhesive sealant applied) after 6 kg of force was applied during
      simulated intraoral movements. Movements were generated over two simulated time
      periods, representing 1 and 6 months. There was no significant decrease (alpha <
      .05) in the torque required to loosen the screws after either time period when
      using Calcitek Omnilock or Stryker Minimatic. The Core-Vent Bio-Vent specimens,
      however, exhibited a significant decrease (alpha < .05) in the amount of torque
      required to loosen the screws at the 1-month test period only. The addition of
      adhesive sealant significantly increased (alpha < .05) the amount of torque
      necessary to loosen the screws only in the Core-Vent specimens.

PMID- 8297453
TI  - Assessment of a recently introduced fluoroelastomeric soft lining material.
AB  - The clinical usefulness of soft denture-lining materials is well established.
      This laboratory-based comparative study of a heat-processed silicone (Molloplast
      B) and a recently introduced fluoroelastomeric soft lining material (Novus)
      evaluated absorption behaviour in distilled water; the softness of the materials
      at different thicknesses, both dry and after immersion in water; and their
      compatibility with denture cleansers. A significant absorption of water, greater
      than 5% by weight, was displayed by Novus after 4 months' immersion. The softness
      of different thicknesses of Novus (up to 1.35 mm) increased significantly upon
      immersion over the same period when compared to Molloplast-B, which showed no
      change. Some surface degradation of Novus was evident upon exposure to denture
      cleansers that was not apparent with Molloplast-B.

PMID- 8297454
TI  - Occlusion for maxillary dentures opposing osseointegrated mandibular prostheses.
AB  - This paper presents a combination of several occlusal concepts designed to
      contribute to the successful use of maxillary dentures in opposition to
      osseointegrated mandibular prostheses. To ensure a positive outcome when
      designing such an occlusion, three factors must be considered: patient
      satisfaction, maxillary anterior bone preservation, and mandibular arch
      shortening. It is recommended that for centric occlusion the molars have a
      lingual contact occlusion, the premolars have a buccal contact occlusion, and the
      anterior teeth have an open occlusal relationship. For an eccentric occlusion, a
      balanced articulation is favored instead of mutually protected occlusion.

PMID- 8297455
TI  - A retrospective study on the maintenance and repair of implant-supported
      prostheses.
AB  - This study reviewed the prosthodontic treatment and aftercare required by 29
      patients with 32 implant-supported prostheses (12 fixed and 20 removable) placed
      on 107 implants. Patients were followed for 4 to 39 months. The majority of
      implant-supported prostheses (53%) were placed in the mandible. Visual analogue
      scales were used by the patients to rate their satisfaction with their prostheses
      and their chewing ability. Approximately one third of the patients studied
      required three or more relines of their existing dentures between first- and
      second-stage surgeries, while over half of the definitive implant-supported
      prostheses required a major adjustment or repair. Removable prostheses required
      78% of the total repairs and accounted for 80% of those prostheses that needed
      repeated repairs. In general, patients were very satisfied with their implant
      supported prostheses, but 17% complained of mild speech difficulties and 7% noted
      slight difficulty in cleaning their fixed prostheses. Overall, the short-term
      prosthetic management required for the implant-supported prostheses in this study
      was substantial, particularly with the removable prostheses, and this should be
      taken into account when evaluating prosthetic options.

PMID- 8297456
TI  - Implant treatment in elderly patients.
AB  - A group of 48 patients, all more than 80 years old (mean age 82.7 years) at first
      implant surgery, who received a total of 254 implants, were followed in one
      clinical center. Of the exposed implants, 6 of 238 (2.5%) were found to be loose
      at second-stage surgery, and another 3 implants were lost during the follow-up
      period. Most patients had minimal postplacement problems, similar to what has
      been observed in younger patients. However, some patients (10%) experienced
      obvious problems with general adaptation and muscle control, which has not been
      observed in younger patients.

PMID- 8297457
TI  - The fracture resistance of all-ceramic crowns on supporting structures with
      different elastic moduli.
AB  - This in vitro study evaluated the fracture resistance of all-ceramic crowns as a
      function of the elastic modulus of the supporting die. All-ceramic crowns were
      made for dies with three different elastic moduli and two different crown
      lengths. The occlusal surface was loaded in compression with a 12.7-mm steel
      ball. The fracture load increased markedly with the increase in elastic modulus.
      The largest increase was seen when only the occlusal surface of the crown was
      covered. The characteristic fracture load of the complete-crown restorations was
      more than double that of the occlusal-cover restorations in the dies with the
      lowest modulus of elasticity, while for the dies with the highest modulus of
      elasticity the difference in the characteristic fracture load for the two
      configurations was not significant.

PMID- 8297458
TI  - Effects of two methods of moisture control on marginal microleakage between resin
      composite and etched enamel: a clinical study.
AB  - Visible light-polymerized resin composite tabs were bonded to the flattened, acid
      etched surface of teeth that were scheduled for extraction. Half of the teeth
      (group I) were isolated with cotton rolls in conjunction with a saliva ejector.
      The remaining teeth (group II) were isolated using a rubber dam. Both methods of
      isolation were used for each patient so that to some extent all patients served
      as their own controls. Following extraction, all samples were thermocycled 500
      times alternating between 6 degrees C and 60 degrees C, after which they were
      immersed in 5% methylene blue for 4 hours. Each tooth was then mounted in acrylic
      resin and sectioned on a hard tissue microtome. Microleakage was assessed using a
      light microscope at x 20 magnification. The use of rubber dam isolation resulted
      in less microleakage at the enamel resin interface.

PMID- 8297459
TI  - Disinfection of impression materials to prevent viral cross contamination: a
      review and a protocol.
AB  - Hepatitis B and the acquired immunodeficiency syndrome are serious diseases
      because of their poor prognoses. The increasing awareness of the latter has
      highlighted the need for adequate precautions against cross contamination.
      However, the risk to dental personnel is still far higher from hepatitis B than
      it is from the human immunodeficiency virus, and the hepatitis virus is more
      transmissible, especially because it occurs in saliva. The principal potential
      route of transmission to dental laboratory personnel is via infected impressions.
      A number of papers have appeared in the literature examining the effects of
      various disinfecting and sterilising procedures on the accuracy and surface
      quality of impression materials. This paper reviews this literature and draws
      upon the findings to recommend a protocol for the handling of impressions to
      prevent cross contamination.

PMID- 8297460
TI  - An evaluation of three methods of bonding resin composite to stainless steel.
AB  - Three bonding agents were evaluated to determine which were most effective in
      enhancing the bond of resin composite to stainless steel. A light-activated resin
      composite was bonded to a total of 60 stainless steel specimens using Panavia,
      Cover-Up, or Silicoating. Tensile bond strength measurements revealed that all
      three agents provide a satisfactory means of increasing adherence of the esthetic
      veneer without decreasing bonding through thermocycling of the specimens. Panavia
      and Cover-Up were significantly more effective than Silicoating and appear to be
      easier to use.

PMID- 8297461
TI  - Hepatic arterial variations and liver-related diseases of 100 consecutive donors.
AB  - We prospectively studied anatomical variations and diseases of the liver in 100
      consecutive donor operations during a period of 1 year. The "normal" arterial
      anatomy with a single hepatic artery (HA) from the celiac trunk was seen in 76%
      of all cases. Seven of twelve different major variations of the HA may be
      considered as "rare", one of which cannot be found in the earlier literature.
      During harvesting, 6% of the livers were discarded, 3% on the basis of infection
      and 1% because of a polycystic disease. Two cases were rejected as the liver was
      found to be severely hypoperfused or hypoxic in an otherwise stable donor. Severe
      steatosis was macroscopically and histologically diagnosed in 3% of the cases,
      and in three donors a benign tumour was found in the liver or in the gall
      bladder. Two primarily nonfunctioning livers in the present series of 94
      recipient operations were retrieved from this group of severely steatotic livers.
      As the donor liver was totally "normal" in only 2 out of 3 of the cases, the
      present study underlines the importance of searching for extremely variable
      anomalies of the HA and for liver-related diseases during organ harvesting.

PMID- 8297462
TI  - Evidence that both cyclosporin and azathioprine prevent warm ischemia reperfusion
      injury to the rat liver.
AB  - The present work was undertaken to study whether the immunosuppressive agents
      cyclosporin (CyA) and azathioprine (AZA) ameliorate hepatic injury after warm
      ischemia. A temporary, normothermic liver ischemia was induced in female Sprague
      Dawley rats. The rats were treated with CyA (10 mg/kg per day p.o.), AZA (8 mg/kg
      per day p.o.), or vehicles for 4 days before surgery. Seven-day survival rates
      after 60 min of ischemia improved significantly with CyA (76.2%, P < 0.005) and
      AZA (78.6%, P < 0.001) treatment, compared with 43.0% for the control group. The
      highest levels of serum aminotransferases in the treatment groups tended to be
      lower than those in the control group. The peak values for the percentage of
      liver necrosis, an indicator of the extent of hepatic necrosis, in the animals
      treated with CyA (26.1% +/- 7.2%, mean +/- SEM) and AZA (32.1% +/- 5.7%) were
      significantly lower than in the control group (47.4% +/- 3.7%). Lipid
      peroxidative damage after reperfusion, assessed as the hepatic malondialdehyde
      (MDA) concentration, was significantly suppressed by pretreatment with CyA and
      AZA. Histological findings coincided with other parameters. This study
      demonstrates that both AZA and CyA have beneficial effects on normothermic liver
      ischemia in rats. It is suggested that the diminished lipid peroxidative damage
      with these agents might be one of the mechanisms responsible for this.

PMID- 8297463
TI  - Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney
      transplantation.
AB  - We studied the effects of a single intravenous injection of rabbit ATG (RIVM,
      Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h
      after kidney transplantation on graft survival, rejection incidence, T-cell
      subsets, and cost-effectiveness. A total of 58 (37 male/21 female) consecutive
      renal allograft recipients were entered in this trial. Treatment results were
      compared with 56 patients treated with intravenous cyclosporin (CyA). In all
      patients concomitant medication consisted of steroids and azathioprine, followed
      by oral CyA. Following rabbit ATG, T cells (WT31) quickly disappeared from the
      peripheral blood and a return to greater than 100/mm3 was observed at a median of
      7 (range 3-21) days. Graft survival was the same in both groups, as was the
      incidence of primary nonfunction. The rate of acute rejection was significantly
      lower in the rabbit ATG-treated patients (12% vs 50%). We conclude that a single
      shot of rabbit ATG is an attractive, easy, and cost-effective induction scheme
      with a low incidence of delayed graft function and acute rejection episodes. A
      relatively high incidence of vascular thrombosis of the graft, however, warrants
      further study before this treatment regimen can be generally applied.

PMID- 8297464
TI  - Cytomegalovirus infection accelerates cardiac allograft vasculopathy: correlation
      between angiographic and endomyocardial biopsy findings in heart transplant
      patients.
AB  - In order to determine the impact of cytomegalovirus (CMV) infection on cardiac
      allograft vasculopathy (CAV), we quantitated angiograms and endomyocardial biopsy
      (EMB) specimens obtained from 53 heart transplant recipients. CMV infection was
      particularly associated with the development of discrete stenosis in major branch
      vessels (P < 0.03). Also, the number of diffusely affected vessel segments was
      significantly higher in CMV patients than in CMV-free recipients after the 2nd
      postoperative year (P < 0.05). The EMB histology correlated well with
      angiography. Significantly higher levels of arteriolar endothelial cell
      proliferation and intimal thickness were recorded in biopsies of CMV patients
      than in those of CMV-free recipients during the 1st postoperative year (P < 0.02
      and P < 0.005, respectively). The CMV-associated vascular changes in EMB
      histology clearly preceded angiographically detectable CAV findings. Taken
      together, CMV infection accelerated heart allograft arteriosclerosis. The
      histological changes appeared prior to changes detected by coronary angiography.
      The CMV effect was particularly pronounced during the first 2 post-transplant
      years but leveled off thereafter. Thus, CMV-accelerated allograft
      arteriosclerosis may be linked in particular with early graft loss of CMV
      infected heart transplant recipients.

PMID- 8297465
TI  - Renal transplantation in patients with bilateral renal carcinoma--how long should
      we wait?
AB  - Patients with bilateral renal carcinoma or malignancy in a solitary kidney are
      best managed by radical nephrectomy with subsequent dialysis and transplantation.
      Because of the risk of recurrence of the tumour, the timing of the transplant
      procedure is important. We report on two patients with bilateral renal carcinoma
      who were subjected to radical nephrectomy and then managed with dialysis and
      transplantation within 6 months.

PMID- 8297466
TI  - Kidney transplantation in patients previously treated for renal carcinomas.

PMID- 8297467
TI  - Liver transplantation for PNH with Budd-Chiari syndrome. A case report.
AB  - A 54-year-old male patient with end-stage liver failure from Budd-Chiari syndrome
      due to paroxysmal nocturnal hemoglobinuria (PNH) underwent liver transplantation
      (OLT) in 1989. Retransplantation became necessary 1 year later when thrombotic
      occlusion of the portal vein and common hepatic artery led to graft loss after
      withdrawal of anticoagulation therapy because of several gastrointestinal
      bleeding episodes. The patient is now alive 3 years after the first OLT. To the
      best of our knowledge and according to the literature, this is, to date, the
      longest that any PNH patient has survived after liver transplantation. Although
      the course of this patient was complicated in a way similar to that reported for
      other cases in the literature, patients with PNH should not, in principle, be
      excluded from liver transplantation. Lifelong anticoagulation with coumarin and
      the use of steroids together with cyclosporin reduce the risk of recurrent
      thrombosis and PNH crises.

PMID- 8297468
TI  - Developmental regulation of bovine insulin-like growth factor-II (IGF-II) gene
      expression: homology between bovine transcripts and human IGF-II exons.
AB  - Initial observations have indicated similarities between bovine and human IGF-II
      production during development. The aim of the present study was to investigate
      whether cattle could provide an experimental model that would mimic the complex
      pattern of human IGF-II gene expression. Expression of bovine IGF-II gene during
      development was studied by RNA hybridization using various human IGF-II probes.
      In fetal tissues and in adult muscle, the bovine IGF-II gene was expressed as a
      family of eight transcripts ranging in size from 5.2 to 1.1 kb. In adult bovine
      liver, a major IGF-II transcript of 4.4 kb was expressed that could not be
      detected in any fetal or adult extra-hepatic tissue. During fetal life,
      quantitative IGF-II mRNA expression differed in liver and muscle, and the
      relative amounts of the different transcripts varied with the tissue of origin.
      These observations suggest that the regulation of bovine IGF-II gene expression
      is specific to the stage of development and the tissue concerned. Moreover its
      pattern is very similar to that in its human counterpart. In order to identify a
      putative homology between human and bovine gene structures, bovine mRNAs were
      examined for cross-hybridization with various non-coding exons of the human gene.
      Cross-hybridization was detected with human untranslated exons 5 and 6,
      suggesting the presence of two distinct promoters similar to the human promoters
      P3 and P4. The 4.4 kb mRNA species expressed in adult bovine liver failed to
      hybridize to a probe for human exons 1 and 2, suggesting that the leader
      sequences of this transcript were different from those present in the human gene.
      Finally, results obtained with a probe containing the 3' untranslated end of exon
      9 suggested the presence of at least two polyadenylation sites in the bovine
      gene. Although differences in IGF-II gene structures were found between cattle
      and man, the similarities in the pattern of gene expression between the two
      species suggest that cattle may be a useful model to investigate some
      developmental aspects of the expression of the human IGF-II gene.

PMID- 8297469
TI  - Pit-1/GHF-1 expression in pituitary adenomas: further analogy between human
      adenomas and rat SMtTW tumours.
AB  - Adenomas can develop from each cell type of the anterior pituitary. In the normal
      pituitary, three of these cells types, the GH-, prolactin- and TSH-secreting
      cells, express the transcription factor Pit-1/GHF-1 which is responsible for
      prolactin and GH (and probably TSH) cell commitment, differentiation, probably
      proliferation and gene expression. We have analysed the expression of Pit-1/GHF-1
      in a panel of human pituitary adenomas. All GH-, prolactin- and TSH-expressing
      adenomas studied expressed the Pit-1/GHF-1 factor, as demonstrated by in-situ
      hybridization and immunocytochemistry. The expression was higher in adenomas than
      in normal human pituitary. In contrast, ACTH- and LH-FSH-secreting and non
      secreting adenomas were negative. Seven transplants of the spontaneous rat
      prolactinoma SMtTW were also investigated and all were found to be positive. This
      further stresses the analogy between these tumours and human prolactinomas. Taken
      together, the data confirm that Pit-1/GHF-1 expression is restricted to GH-,
      prolactin- and TSH-expressing cells, and the increased expression in adenomas is
      compatible with a role of Pit-1/GHF-1 in cell proliferation.

PMID- 8297470
TI  - Characterization of the mouse thyrotrophin-releasing hormone receptor gene: an
      exon corresponds to a deletion in the rat cDNA.
AB  - The cloning and characterization of the mouse TRH receptor (TRH-R) gene revealed
      an untranslated exon (exon 1), a single intron and an upstream dinucleotide
      repeat sequence (d(TG)16.d(AG)21) in the 5' untranslated region (UTR). The coding
      region was contained almost entirely on a second exon (exon 2), with the final
      amino acid and stop codon at the COOH terminus of the gene encoded by a third
      exon (exon 3) flanked by two introns. The 3' UTR was contained on the remainder
      of exon 3 and on the final exon (exon 4). Exon 3 (228 bp) corresponds exactly to
      a 228 bp deletion that exists in the rat TRH-R cDNA, but not in the mouse cDNA.
      The mouse TRH-R cDNA encodes a protein of 393 amino acids which is 96% homologous
      to the rat TRH-R protein of 412 amino acids, but is 19 amino acids shorter at its
      COOH terminus. The coding sequence for these 19 amino acids (plus 1 extra amino
      acid) does exist in the mouse TRH-R gene, but the sequence is encoded by exon 4,
      separated from the rest of the coding region by the stop codon and 223 bp of 3'
      UTR on exon 3. Splicing of exon 3 in the mouse TRH-R gene would remove the last
      amino acid, the stop codon and the 223 bp of 3' UTR, allowing transcription to
      continue into the 3' UTR on exon 4, which encodes the 19 extra amino acids found
      in the rat cDNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297471
TI  - Transferrin gene expression in the mammary gland of the rat. The enhancing effect
      of 17 beta-oestradiol on the level of RNA is tissue-specific.
AB  - We have investigated the physiological factors which regulate transferrin gene
      expression in the mammary gland of the rat. Our studies by dot blot analysis have
      demonstrated that multiple doses of 17 beta-oestradiol (OE2; 0.5 mg/kg per day
      for 3 days) elicit a specific 3.5-fold increase in the transferrin mRNA levels in
      the mammary glands of virgin rats. The hormonal action of OE2 in mammary tissue
      was specific for the transferrin gene, as judged by hybridization with beta-actin
      cDNA. The accumulation of transferrin mRNA induced by OE2 treatment was similar
      to the developmentally regulated expression of the gene observed during the
      reproductive cycle. The steady-state level of mammary transferrin mRNA increased
      by up to 4.5-fold at day 21 of lactation, when compared with virgin and pregnant
      rats. Our results show that the pattern of transferrin gene expression is
      different in mouse and rat mammary glands. The specific response of the
      transferrin gene to OE2 was not found in the liver or in the uterus. In the
      uterus alone, OE2 produced a significant increase in the content of nucleic acids
      and also induced the accumulation of transferrin and beta-actin mRNAs. We have
      detected for the first time an induction of transferrin gene expression in the
      mammary gland in response to OE2, and these results support the view that the
      pattern of transferrin gene multi-modulated expression is tissue- and species
      specific.

PMID- 8297472
TI  - Expression of a functional thyroglobulin fragment in a baculovirus system.
AB  - The synthesis is described of an N-terminal thyroglobulin (Tg) polypeptide of 27
      kDa, which is capable of hormonogenesis, in a baculovirus system. This
      polypeptide was made using a 657 bp Tg cDNA cloned from human thyroid RNA by a
      polymerase chain reaction method. The cDNA contained the information for the Tg
      signal peptide, the N-terminally located site for thyroid hormone formation and,
      at the 3' end, a sequence coding for six histidine residues. The fragments
      produced were purified using a nickel-nitrilotriacetic acid column using these
      six histidine residues. The products were analysed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis and showed two glycosylated fragments of 32
      and 34 kDa, both of which started with asparagine. Iodination of the fragments
      with lactoperoxidase in vitro resulted in the formation of thyroxine (T4). The
      formation rate of T4 in the fragments was about five times lower than that of the
      mature Tg dimer of 660 kDa, but ten times more rapid than in bovine serum albumin
      under the same conditions.

PMID- 8297473
TI  - Expression of growth hormone genes in Atlantic salmon.
AB  - Atlantic salmon (Salmo salar) possess two genes encoding GH. We have investigated
      the expression of these two genes in the salmon pituitary. The transcriptional
      start site was localized 64 nucleotides upstream of the first methionyl codon
      using primer extension and 5' specific polymerase chain reaction (PCR) assays.
      Northern analysis revealed a major Atlantic salmon GH (salGH) transcript band of
      approximately 1400 nucleotides. As coexpression of the salGH genes is not
      discernible by transcript length, other techniques were used to assess gene
      activity; RNase protection analysis revealed GH transcript heterogeneity, while
      reverse transcription-PCR assays detected transcripts from both genes at
      approximately equivalent amounts. The encoded salGH protein, generated in vitro
      and by Escherichia coli, shares electrophoretic and immunoreactive identity with
      native pituitary salGH.

PMID- 8297474
TI  - Isolation- and dehydration-induced changes in neuropeptide gene expression in the
      sheep hypothalamus.
AB  - Changes in neuropeptide gene expression in the hypothalami of sheep subjected to
      psychological stress (isolation, 1 h; n = 3) or dehydration (48 h; n = 3) were
      examined using in-situ hybridization histochemistry. Compared with non-stressed
      euhydrated control animals (n = 3), isolation induced significant accumulation of
      mRNA for corticotrophin-releasing hormone, pro-enkephalin and pro-dynorphin (DYN)
      in the paraventricular nucleus (PVN), but no change in mRNA content within the
      supraoptic nucleus (SON). By contrast, dehydration significantly increased DYN
      mRNA in the magnocellular neurones of the PVN and SON. However, neither isolation
      nor dehydration altered the expression of mRNA for vasopressin (AVP) in either
      the PVN or the SON. These results indicate that in the ovine hypothalamus (1)
      stress represents a powerful stimulus to co-ordinated neuropeptide synthesis and
      (2) expression of DYN mRNA and AVP mRNA may be independently regulated during
      changes in plasma osmolality.

PMID- 8297475
TI  - Modulation of human DNA methyltransferase activity and mRNA levels in the
      monoblast cell line U937 induced to differentiate with dibutyryl cyclic AMP and
      phorbol ester.
AB  - The regulation of DNA (cytosine-5) methyltransferase (DNA MeTase) enzyme activity
      and gene expression was examined in the monoblastoid U937 cell line induced to
      differentiate with either dibutyryl cyclic AMP (dbcAMP) or phorbol ester. dbcAMP
      treatment was found to cause the rapid (< 4 h) suppression of DNA MeTase specific
      activity, with no DNA MeTase activity detectable after 10 h. Equally, no DNA
      MeTase activity was detectable in nuclear extracts of fresh peripheral blood
      monocytes. Using both a U937 DNA MeTase cDNA and a mouse DNA MeTase cDNA as
      probes, steady-state levels of DNA MeTase mRNA were found to decline sharply
      between 4 and 15 h after dbcAMP treatment. No DNA MeTase mRNA was detectable
      after 20 h of dbcAMP treatment. Nuclear run-on analysis showed there to be only a
      small (40%) suppression of DNA MeTase gene transcription in cells treated with
      dbcAMP for 24 h, implying a role for post-transcriptional processes in the
      regulation of DNA MeTase mRNA levels. The observed decline in DNA MeTase
      activity/mRNA levels appeared to precede the dbcAMP-induced arrest in DNA
      replication, as judged by the incorporation of tritiated thymidine into DNA. In
      contrast to the effect of dbcAMP, treatment of U937 cells with the phorbol ester
      12-O-tetradecanoyl phorbol-13-acetate (TPA) led to an overall stimulation of DNA
      MeTase specific activity. The TPA response was found to be complex and broadly
      consisted of an early (0-15 h) burst of DNA MeTase activity followed by a more
      gradual sustained increase in DNA MeTase activity after prolonged (16-40 h) TPA
      treatment. The early phase of high DNA MeTase activity was not mirrored by an
      increase in steady-state levels of DNA MeTase mRNA, as judged by Northern blot
      analysis. However, a substantial induction of DNA MeTase mRNA levels was observed
      after 20-24 h of TPA treatment. Nuclear run-on analysis showed this not to be due
      to any significant increase in DNA MeTase gene transcription. The observed
      increases in DNA MeTase activity/mRNA levels were observed whilst cells were
      undergoing deproliferation. Interestingly, the addition of TPA and more
      physiological protein kinase C (PKC) activators, such as diacylglycerol and
      phosphatidylserine, to DNA MeTase-enriched nuclear extracts generated a 4.5-fold
      and a 1.5-fold increase in DNA MeTase specific activity respectively. The TPA
      induced stimulation of DNA MeTase activity could be inhibited by the PKC
      inhibitor H-9, implicating a role for PKC in the regulation of DNA MeTase
      activity in vivo.

PMID- 8297476
TI  - The porcine insulin-like growth factor-I gene: characterization and expression of
      alternate transcription sites.
AB  - Genomic DNA encoding the 5' region of the porcine IGF-I gene was cloned and
      sequenced and shown to be highly homologous to that of man, rats and sheep. Two
      leader exons (exons 1 and 2), which are alternately spliced to exon 3 (encoding
      part of the mature IGF-I molecule), were identified by RNase protection analysis.
      In both cases, transcription initiates upstream from exons 1 and 2 at multiple
      dispersed start sites to yield two distinct IGF-I mRNA transcript classes (1 and
      2) which differ in the precursor peptides predicted from their individual leader
      sequences. The expression of class 1 and 2 transcripts was measured in liver and
      muscle RNA from two groups of 2-month-old pigs whose energy status had been
      manipulated within physiological limits to produce marked differences in plasma
      IGF-I levels and growth rates. For this purpose, RNase protection probes were
      developed that contained the individual leader exons 1 and 2 linked separately to
      the common exon 3, so that class-specific and total IGF-I gene expression could
      be determined in a single assay. At normal plasma IGF-I concentrations (200
      ng/ml), class 1 and 2 transcripts comprised 81 and 19% respectively of total
      liver IGF-I mRNA, while at a lower plasma concentration (90 ng/ml) the
      corresponding values were 95 and 5% respectively. Although both classes of
      transcript declined with the decrease in plasma IGF-I, the relative drop in
      levels of class 2 transcripts (84%) was substantially greater than that of class
      1 (54%). In longissimus dorsi, cardiac and soleus muscles IGF-I mRNA was
      predominantly of class 1 and did not change in response to decreased plasma IGF
      I. This suggests that liver-derived endocrine IGF-I has an important function in
      the regulation of muscle growth and that class 2 IGF-I transcripts are more
      sensitive to conditions that promote optimal growth.

PMID- 8297477
TI  - A trans-acting locus regulates transcriptional repression of the female-specific
      steroid 15 alpha-hydroxylase gene in male mice.
AB  - Steroid 15 alpha-hydroxylase (P450(15 alpha)) is a female-specific enzyme in the
      livers of many inbred mice including DBA/2J. Run-on assays using liver nuclei
      from GH-deficient Little mice indicated that the P450(15 alpha) gene is
      transcriptionally repressed by GH in male mice. BALB/cJ is a variant strain in
      which the gene is expressed in the males as well as in the females. Genetic
      crosses between DBA/2J and BALB/cJ indicated that expression of the P450(15
      alpha) gene in BALB/cJ males is inherited as a recessive trait and is regulated
      by a single locus. The parental origin of the P450(15 alpha) genes, determined
      using restriction site polymorphism in the exons of the P450(15 alpha) genes,
      divided the F2 males expressing the P450(15 alpha) gene into three phenotypes at
      a ratio of 1:1:2, the individuals expressing the gene from only BALB/cJ or DBA/2J
      and the individuals expressing the genes from both parents respectively. The
      results indicate that the repression of the P450(15 alpha) gene in male mice is
      regulated by a trans-acting regulatory locus between the DBA/2J and BALB/cJ
      pairs. Because hypophysectomy derepressed the P450(15 alpha) gene in F1 males and
      GH repressed the gene in hypophysectomized F1 males, the hormone appears to
      regulate gene repression through a trans-acting locus, named GH-dependent
      repression, GDR.

PMID- 8297478
TI  - Distribution of insulin-like growth factor-I receptor mRNA in rat brain.
      Regulation in the hypothalamo-neurohypophysial system.
AB  - The distribution and regulation of mRNA for the IGF-I receptor (IGF-I-R) in the
      adult rat brain were studied by in-situ hybridization with a 35S-labelled cRNA
      probe. The pituitary gland showed a strong hybridization signal in the pars
      tuberalis (the surface of the median eminence), pars distalis and pars
      intermedia. Within the brain, a strong hybridization signal was found in the
      circumventricular organs, olfactory bulb, hippocampus, cerebellum and
      hypothalamus. IGF-I-R mRNA was consistently found in cell bodies of the
      hypothalamo-neurohypophysial system. Six days of intermittent salt-loading
      resulted in an increase in IGF-I-R gene expression in the supraoptic nucleus. The
      increase in IGF-I-R mRNA was accompanied by a high expression of c-Fos
      immunoreactivity in the same cells. The presence and regulation of IGF-I-R mRNA
      in the hypothalamus suggest that IGF-I may affect the local plasticity or
      modulation of activated magnocellular neurones by an autocrine or paracrine
      action through specific receptors in the hypothalamo-neurohypophysial system.

PMID- 8297479
TI  - Transforming growth factor-beta 1 expression in Syrian hamster cheek pouch
      carcinogenesis.
AB  - The expression pattern of transforming growth factor-beta 1 (TGF-beta 1) during
      the stages of complete carcinogenesis in the hamster cheek pouch model was
      studied. The right cheek pouches of 18 male hamsters were treated with 0.5%, 7,12
      dimethylbenz[a]anthracene (DMBA) for 16 wk. TGF-beta 1 was detected
      immunohistochemically in the resulting samples with two different polyclonal
      monospecific antibodies that recognize intracellular and extracellular forms of
      TGF-beta 1. In the normal cheek pouch, extracellular protein stained the corium
      strongly, but the reaction was not evenly distributed. As treatment progressed,
      the reaction increased in both area and intensity; the peak was reached at 8 wk.
      Intracellular TGF-beta 1 expression followed a similar pattern, with a peak at 4
      wk of treatment. The results of northern blot analysis were concordant with the
      immunohistochemical results. Overexpression of TGF-beta 1 was also observed in
      the malignant tumors, but only the extracellular form of the protein was present;
      intracellular TGF-beta 1 was not detected in these tumors. The expression of TGF
      beta 1 in this carcinogenesis model seems to have two formal stages, the first
      being an overexpression step as a reaction to the uncontrolled growth and the
      second being one in which tumors have no internal expression of TGF-beta 1 but in
      which external protein accumulates in the surrounding stroma. A possible
      explanation of this paradox may be that TGF-beta 1 has functions other than its
      growth-repressing activity.

PMID- 8297480
TI  - Increased expression of stromelysin-3 in basal cell carcinomas.
AB  - We examined the expression of two groups of matrix metalloproteinases (MMPs),
      stromelysin and interstitial collagenase, in human skin cancer by northern blot
      analysis and in situ hybridization. Stromelysin-3 (ST-3) mRNA was overexpressed
      more than tenfold in 17 of 19 (89%) specimens of basal cell carcinoma (BCC) but
      in only three of 13 (23%) cutaneous squamous cell carcinomas (SCCs). Stromelysin
      1 and -2 (ST-1/2) mRNA was overexpressed in three of 19 (16%) BCC and three of 13
      (23%) SCC. Collagenase mRNA was overexpressed in nine of 19 (47%) BCC and three
      of 13 (23%) SCC. No mRNA for ST-3, ST-1/2, or collagenase was detected by
      northern analysis in 21 specimens of adjacent normal skin. Because of these
      findings, we examined the specific location of the ST-3 mRNA in BCC specimens by
      in situ hybridization. ST-3 mRNA was particularly abundant in the characteristic
      stroma adjacent to the invasive basaloid tumor islands of the BCC and absent in
      the malignant cells. Moreover, ST-3 mRNA was expressed and induced by phorbol
      ester treatment in adult dermal fibroblasts but not in keratinocytes. In vitro
      studies have shown that MMPs are involved in the degradation of extracellular
      matrix molecules. Our finding of ST-3 mRNA overexpression in 17 of 19 (89%) BCC
      specimens is consistent with a role for this molecule in local invasion of stroma
      by BCC. Our in situ hybridization data suggested that while ST-3 is not expressed
      by malignant basal cells themselves, these tumor cells may induce the expression
      of ST-3 in adjacent nonmalignant stromal elements such as fibroblasts.

PMID- 8297481
TI  - Evidence of two separate mechanisms for the decrease in aryl sulfotransferase
      activity in rat liver during early stages of 2-acetylaminofluorene-induced
      hepatocarcinogenesis.
AB  - Enzymatic and immunohistochemical experiments were conducted to evaluate the
      mechanistic basis for the downregulation of the important
      detoxication/bioactivation enzyme aryl sulfotransferase IV (AST IV) during 2
      acetylaminofluorene (2AAF)-induced hepatocarcinogenesis. To distinguish between
      possible genotoxic and cytotoxic actions of 2AAF, three different dietary
      protocols were used in these experiments: group 1 received 2AAF for 12 wk, group
      2 received 2AAF for 3 or 6 wk and then a control diet lacking xenobiotics for 3
      or 6 wk, and group 3 received 2AAF for 3 or 6 wk and then phenobarbital for 3 or
      6 wk. When hepatic AST IV activity was assessed, N-hydroxy-2AAF sulfotransferase
      activity was found to decrease 80-90% in response to 2AAF feeding, but activity
      recovered to essentially normal levels in the livers of rats subsequently placed
      on either control diets or diets with phenobarbital, suggesting a reversible
      cytotoxic mechanism for loss of AST IV activity. However, when liver sections
      from the rats were evaluated immunohistochemically, two distinct patterns were
      detected for the downregulation of AST IV activity. In the livers of rats
      administered only 2AAF (group 1), a general pattern of overall downregulation of
      AST IV expression was observed throughout the liver and among most but not all
      newly developed nodules. In tissue sections from rats initially fed 2AAF and then
      placed on a control diet (group 2) or a diet with phenobarbital (group 3), the
      nodules continued to show low levels of AST IV expression, while expression in
      the areas surrounding nodules returned to the normal, high levels. In addition,
      among those rats fed 2AAF for just 3 wk and then control diet or diet containing
      phenobarbital for 6 wk, only rats fed phenobarbital developed altered foci that
      stained weakly for AST IV expression. These results show that there were two
      kinds of 2AAF-mediated decrease in hepatic AST IV activity: a general overall
      loss of AST IV expression dependent on administration of 2AAF and reversible upon
      removal of 2AAF from the diet and a loss of AST IV expression among newly
      developed liver foci and nodules that persisted in the absence of 2AAF
      administration and appeared to be a property of 2AAF-induced subpopulations of
      cells. These patterns may correspond, respectively, to cytotoxic and genotoxic
      mechanisms of 2AAF action.

PMID- 8297482
TI  - Expression of myc, fos, and Ha-ras in the livers of furan-treated F344 rats and
      B6C3F1 mice.
AB  - Furan administered by gavage for 2 yr has been reported to induce hepatocellular
      carcinomas in male and female B6C3F1 mice and in male but not female F344 rats.
      Chronic exposure studies in our laboratory using bioassay conditions showed
      extensive hepatocellular toxicity and sustained increases in regenerative cell
      proliferation after 1, 3, and 6 wk of treatment in male and female rats and male
      mice. Altered expression of growth-control genes associated with this
      hyperproliferative state may enhance the susceptibility of these genes to
      mutation or may provide a selective growth advantage to preneoplastic cells.
      Quantitative northern blot analysis of mRNA was used to examine the expression of
      the oncogenes myc, fos, and Ha-ras in the livers of animals treated with furan.
      In male rats, a single administration of 30 mg/kg furan produced necrosis and a
      subsequent wave of cell proliferation 48 h after treatment and induced transient
      peaks in the expression of myc, fos, and Ha-ras 6-24 h after treatment. In male
      rat liver from our cell proliferation studies, only a slight increase in myc
      expression was seen at the end of week 1 of treatment. However, beginning at week
      3 and increasing at week 6, up to a 15-fold increase over control values was
      observed in the expression of myc in the treated animals. The only other notable
      increase in expression observed in any animals from the cell proliferation study
      was a threefold increase in myc at week 6 in treated female rats. The absence of
      an increase in Ha-ras expression in the male mouse liver suggests that the unique
      pattern of Ha-ras mutations previously reported in furan-induced mouse liver
      tumors is not due to increased mutational susceptibility related to
      overexpression of this gene. The lack of sustained expression of myc, fos, and Ha
      ras in rapidly proliferating liver suggests that continuous expression of these
      genes is not necessary to maintain increased rates of cell replication. The large
      increase in myc expression in male but not female rats suggests an adaptive
      change that may be related to the sex-specific incidence of furan-induced
      hepatocellular carcinomas in rats.

PMID- 8297483
TI  - G-->A mutations in p53 and Ha-ras genes in esophageal papillomas induced by N
      nitrosomethylbenzylamine in two strains of rats.
AB  - In human esophageal cancers, no ras gene mutations but a relatively high
      prevalence of p53 gene mutations have been reported. We found a high prevalence
      of point mutations in Ha-ras and p53 genes in N-nitrosomethylbenzylamine (NMBA)
      induced esophageal tumors in two strains of rats (BD VI and F344). Our analysis
      showed the point mutation GGA-->GAA (expected from the known mechanisms of action
      of NMBA) at Ha-ras codon 12 in 22 of 46 (48%) and 22 of 38 (58%) papillomas from
      BD VI and F344 rats, respectively. There was no significant difference in the
      prevalence of ras mutations in tumors induced by high doses (5.0 mg/kg) and low
      doses (2.5 mg/kg) of NMBA. Eleven papillomas from each strain were analyzed for
      p53 mutations. The prevalent mutations found were G-->A and C-->T transitions.
      The frequency of p53 mutation was 36% (four of 11) for each strain. No apparent
      hot-spot codon or exon was found in the p53 gene, and two papillomas contained
      double mutations in this gene. The high prevalence of G-->A mutations in the rat
      Ha-ras gene contrasts with that in the human gene, in which no ras mutations have
      been found in primary tumors, and suggests either that the biology of esophageal
      carcinogenesis differs in humans and rats or that nitrosamines are not the major
      etiological risk factor for human esophageal cancers.

PMID- 8297484
TI  - Absence of MDM-2 gene amplification in experimentally induced tumors regardless
      of p53 status.
AB  - To assess the generality of the hypothesis that murine double-minute-2 (MDM-2)
      gene amplification complements the absence of p53 mutation during tumor
      development, we analyzed 143 murine tumors induced by a variety of carcinogenic
      agents in two different mouse strains. Only three of 143 tumors showed p53
      genetic alterations and none showed MDM-2 amplification, indicating the existence
      of alternative pathways that permit tumor cells to bypass p53-MDM-2 control.

PMID- 8297486
TI  - Medicare patients' care in jeopardy.

PMID- 8297485
TI  - Allele loss and point mutation in codons 12 and 61 of the c-Ha-ras oncogene in
      carcinogen-transformed human breast epithelial cells.
AB  - There is significant evidence that the ras oncogene plays a role in experimental
      mammary carcinogenesis; the evidence in human breast cancer, however, is more
      limited. We induced the expression of transformation phenotypes in the human
      breast epithelial cell line MCF-10F with the chemical carcinogens 7,12
      dimethylbenz[a]anthracene, N-methyl-N-nitrosourea, N-methyl-N-nitro-N'
      nitrosoguanidine, and benzo[a]pyrene. This work was designed to clarify whether
      chemically induced neoplastic transformation correlates with alterations in the
      ras gene. MCF-10F cells have two c-Ha-ras alleles, identified by 1.0-kb and 1.2
      kb restriction fragments. Treatment with carcinogens resulted in the loss of one
      of the alleles (1.0 kb). Polymerase chain reaction-amplified DNA from all
      carcinogen-treated cells was analyzed for point mutations in c-Ha-ras at codons
      12 and 61. All of the carcinogens induced a mutation of the remaining allele at
      the first position of codon 12 (GGC-->AGC). Another frequent mutation occurred at
      the first position of codon 61 (CAG-->GAG). The changes in c-Ha-ras were
      associated with the emergence of colony formation in agar-methocel, but no
      specific changes in this gene correlated with the emergence of invasiveness or
      tumorigenesis, indicating that other genes may be involved in the process.

PMID- 8297487
TI  - Using computers as instructional technology in the pressure ulcer field.
AB  - The use of computers by healthcare educators is expanding rapidly because
      computer-assisted instruction reduces learning time, can be accessed at any time,
      and is cost-effective. How to evaluate their cost-effectiveness and suggestions
      for use are presented in detail. The advantages and disadvantages of computer
      assisted instruction (CAI) and interactive videodisc (IVD) technologies are
      reviewed. Several CAI and IVD programs of interest to wound care clinicians are
      described.

PMID- 8297488
TI  - A comparison of the efficacy and cost-effectiveness of two methods of managing
      pressure ulcers.
AB  - To compare the efficacy and the cost-effectiveness of moist gauze dressings and a
      hydrocolloid wafer dressing (DuoDERM CGF), 70 patients with 97 pressure ulcers
      that were stage II and/or stage III were randomly assigned to one of two
      treatment methods: moist gauze dressings or hydrocolloid dressings. Efficacy was
      defined as the number of ulcers that completely healed. In this debilitated,
      poorly nourished group of patients, one ulcer completely healed in the moist
      gauze dressing group, and 11 healed in the hydrocolloid group. The per diem cost
      of the moist gauze dressing was $12.26; the per diem cost of the hydrocolloid
      dressing was $3.55.

PMID- 8297489
TI  - Portrait of practice: a successful approach to preventing heel pressure ulcers
      after surgery.
AB  - Orthopedic surgical procedures requiring a long period of time in the operating
      room and in recuperation can often result in pressure ulcers of the heels. These
      are among the ulcers most difficult to heal; therefore, prevention is important.
      Instituting pre- and postoperative patient education, elevating the heels off the
      mattress, and using heel protectors resulted in 30 patients with total hip
      replacement having no pressure ulcers of the heels.

PMID- 8297490
TI  - Collaborative efforts to change DMERC regulations.

PMID- 8297491
TI  - Case study: eliminating odors from wounds.
AB  - Odor is a major problem with some pressure ulcers and other wounds. This article
      presents a comprehensive list of references and a case study of 13 patients who
      were treated with one topical product (metronidazole gel) to eliminate odor. All
      wounds had large amounts of malodorous drainage when initially assessed and had
      not previously responded to a variety of odor-reducing interventions. A wound
      care protocol was established using 0.75% topical metronidazole gel applied to
      the wound surface. Odor was assessed daily for nine days by a scale adapted from
      Baker and Haig. Malodor associated with each of 13 wounds was decreased following
      the initial treatment with topical metronidazole.

PMID- 8297492
TI  - Do pressure-reducing surfaces change capillary resistance to pressure?

PMID- 8297493
TI  - A novel megakaryocyte potentiator produced by MC-1 human lung cancer cell line.
AB  - The hematopoietic stimulating activity of a human lung cancer cell line, MC-1,
      was investigated. The protein fraction (MC-1 protein) was prepared from the serum
      free culture supernatant of MC-1 cells using hydroxyapatite and concanavalin A
      agarose columns. In serum-containing cultures, MC-1 protein stimulated colony
      formation by megakaryocyte colony-forming units (CFU), erythroid burst-forming
      units and granulocyte/macrophage (GM) CFU. The stimulating effect was strongest
      for megakaryocyte CFU. The factor having megakaryocyte colony-stimulating
      activity was shown to be a protein whose molecular weight was determined to be
      23,000 daltons by gel filtration. By various analyses, this protein was shown to
      be molecularly different from the heretofore-identified cytokines that may affect
      megakaryocytopoiesis, i.e., interleukin-1 (IL-1), IL-2, IL-3, IL-6, IL-7, IL-11,
      granulocyte colony-stimulating factor (CSF), macrophage CSF, GM-CSF, leukemia
      inhibitory factor, stem cell factor and tumor necrosis factor. Under serum-free
      conditions, MC-1 protein augmented murine megakaryocyte colony formation in the
      presence of murine IL-3 and increased the acetylcholinesterase activity of
      purified murine megakaryocytes. It was also shown that MC-1 protein stimulated
      human megakaryocyte colony formation. It was concluded that MC-1 cells produce a
      megakaryocyte potentiator which is molecularly different from any heretofore
      identified cytokines.

PMID- 8297494
TI  - Use of a human microvascular endothelial cell line as a model system to evaluate
      cholesterol uptake.
AB  - CDC/EU.HMEC-1 (HMEC-1) cells provide a reliable source of human microvascular
      endothelial cells free of mycoplasma and viral infection. This cell line has
      potential for use in the further study of the endothelial cell modification of
      low-density lipoproteins and for anticholesterol drug evaluation assays. HMEC-1
      cells will fill a gap that is present for in vitro investigations of cholesterol
      metabolism in conjunction with previously established hepatic, monocytic, or
      macrophage cell lines. This paper presents a simple assay that demonstrates a
      linear uptake of tritiated cholesterol by he HMEC-1 cells and shows that the
      cellular cholesterol load can be regulated using anticholesterol drugs.

PMID- 8297495
TI  - c-fos proto-oncogene transient transcription is negatively affected in the ELa4-2
      transformed rat cell line.
AB  - To study the effects of the regulatory phosphoprotein ICP4 of the Herpes simplex
      virus, (HSV), a DNA tumor virus, on the induction of gene expression by the
      epidermal growth factor (EGF), we have constructed a cell line, ELa4-2, which
      constitutively expresses the a-4 gene product. The ELa4-2 cells are derived from
      the rat fibroblast EL2, in which EGF induces a marked c-fos and c-myc proto
      oncogene transcription. Here we report that in ELa4-2 cells, the gene expression
      induced by EGF was negatively affected in respect to that obtained stimulating
      the parental EL2 cells. In particular, we studied the c-fos and c-myc proto
      oncogene transcription induced by EGF. We found that in ELa4-2 cells the c-fos
      induction was dramatically reduced in comparison with the c-fos induction
      obtained in the parental EL2 cells. On the contrary, the c-myc induction by EGF
      was not affected by the presence of ICP4. Finally, we compared the HSV
      infectivity in ELa4-2 versus the EL2 cells. We showed that the virus growth
      capability was reduced, in the cells expressing ICP4.

PMID- 8297496
TI  - Human endothelial cells as an alternative to DH82 cells for isolation of
      Ehrlichia chaffeensis, E. canis, and Rickettsia rickettsii.
AB  - Ehrlichia chaffeensis, etiologic agent of human ehrlichiosis, and Rickettsia
      rickettsii, etiologic agent of Rocky Mountain spotted fever (RMSF), are both tick
      borne agents that cause nonspecific symptoms that may be indistinguishable from
      each other early in the course of infection. E. canis is a canine pathogen
      closely related to E. chaffeensis and was initially suspected of being the
      causative agent of human ehrlichiosis. If a febrile illness is reported, after
      tick exposure, neither ehrlichiosis nor RMSF can be immediately ruled out. When
      attempts are made to isolate the agent from blood, a very limited amount of blood
      is often available; we, therefore, sought a tissue-culture cell line that would
      support the growth of both R. rickettsii and E. chaffeensis. A newly established
      human microvascular endothelial immortal cell line (CDC/EU.HMEC-1) was evaluated
      for supporting the growth of both agents. Our results demonstrate that HMEC-1
      supports the growth of R. rickettsii, E. chaffeensis, and E. canis and may be a
      useful tool for the isolation of these agents.

PMID- 8297498
TI  - Autumn meeting of the Study Group Neurochemistry. 110th Conference of the
      Gesellschaft fur Biologische Chemie. Berlin, October 4-5, 1993. Abstracts.

PMID- 8297497
TI  - Does a genetically determined aggressive locomotion favour the establishment of
      intracellular macrophage parasites?
AB  - A novel computerized methodology was used to quantify, for the first time, the 3
      dimensional locomotory phenotypes of individual macrophages moving within an
      extracellular matrix-like hydrated collagen lattice/gel. Comparisons between two
      macrophage lines genetically susceptible to intracellular parasites (B10S4 and
      ANA-1) and two genetically resistant (B10R4 and CD2) demonstrated that Bcgs
      alleles consistently endowed macrophages with an outward searching and active
      locomotion, whereas Bcgr imparted a retrocessive phenotype. Several different
      macrophage pathogens may have exploited this genetically determined aggressive
      locomotory behavior of susceptible macrophages to allow them to rapidly enter a
      sanctuary.

PMID- 8297499
TI  - Attenuation of insulin actions in primary rat hepatocyte cultures by phenylarsine
      oxide.
AB  - Phenylarsine oxide (PAO), a trivalent arsenical which complexes vicinal dithiols,
      prevented the action of insulin in primary cultured adult rat hepatocytes.
      Simultaneous short-term treatment of 48-h old cells with insulin and 2 microM PAO
      resulted in complete attenuation of the insulin-dependent increase in the level
      of fructose 2,6-bisphosphate and the activation of phosphofructokinase 2,
      pyruvate kinase, glucokinase flux and glycolysis. Basal rates of glucose
      transport and glycolysis were not affected. PAO also abolished stimulation of
      glycogen synthesis and amino-acid transport and the decrease of glycogenolysis
      evoked by insulin. The 20-fold activation of the insulin receptor tyrosine kinase
      by insulin was, however, not reduced by PAO. The data suggest that in
      differentiated hepatocytes insulin signal transduction involves vicinal
      sulhydryls located at a post-receptor step.

PMID- 8297500
TI  - Characterization of the maltase activity of glucosidase II from rat liver.
      Kinetic model.
AB  - Glucosidase II is a key enzyme in the processing of N-glycoproteins since it
      removes the two glucose residues from the protein-linked oligosaccharide
      Glc2Man9GlcNAc2-R. We have studied the kinetics of the purified enzyme, using
      maltose as substrate. Analysis of data fitting to single and double-hyperbolic
      equations and the Eadie-Hofstee profile indicate that the enzyme has two binding
      (active) sites for the hydrolysis of maltose. The Km and Vmax values for the high
      affinity site were 0.43 mM and 691 mU/mg, respectively, whereas the values for
      the low-affinity site were 57.7 mM and 2888 mU/mg, respectively. The Vmax/Km
      ratios were 1607 and 50.1 ml/min per g for the high- and low-affinity sites,
      respectively. A new kinetic model for this enzyme is proposed from the equilibria
      corresponding to the partial competitive inhibition produced by maltose on p
      nitrophenyl-glucosidase activity. The amino acid composition of the enzyme has
      been established.

PMID- 8297501
TI  - Primary structure of the murine monoclonal IgG2a antibody mAb735 against alpha (2
      8) polysialic acid. 2. Amino acid sequence of the heavy (H-) chain Fd' region.
AB  - The complete amino acid sequence of the Fd' region including the VH part, the CH1
      domain, and the hinge segment of the biologically relevant monoclonal mouse anti
      alpha (2-8) polysialic acid antibody mAb735 is presented. The reduced and
      carboxymethylated H-chain was digested with trypsin and cyanogen bromide. For
      subfragmentation selected peptides were cleaved with thermolysin and
      endoproteinase Asp-N. The generated peptides were isolated by RP-HPLC and
      characterized by sequence analysis, plasma desorption mass spectrometry (PDMS),
      and amino acid analysis. The N-terminal sequence was determined after enzymatic
      deprotection with pyroglutamate aminopeptidase. According to Kabat et al. the
      variable region of the H-chain belongs to the subgroup II. Sequence data from the
      constant region indicate that mAb735 represents the gamma 2a isotype.

PMID- 8297502
TI  - Methanol detoxification by enzyme-loaded erythrocytes.
AB  - Alcohol oxidase (AlOx) from Pichea pastoris (a methylotrophic yeast) was
      encapsulated into human and murine erythrocytes up to 2 units/ml of packed cells.
      This enzyme has a much higher affinity for methanol than for ethanol, thus making
      the loaded erythrocytes useful cellular bioreactors able to catabolize methanol.
      Enzyme-loaded erythrocytes showed an increased rate of the hexose-monophosphate
      shunt activity and a significant methaemoglobin production. However, the in vivo
      survival of these cells does not seem to be significantly affected by methanol
      catabolism. In vivo, mice receiving AlOx-loaded erythrocytes were able to keep
      the blood methanol concentrations below values that were about 50% of those found
      in mice receiving unloaded cells and similar amounts of methanol. Thus AlOx
      loaded erythrocytes may add an important contribution to the detoxification
      protocol against methanol poisoning.

PMID- 8297503
TI  - Biochemical characterization of air-filled albumin microspheres.
AB  - Heating and sonication of a solution of human serum albumin (HSA) yields air
      filled microspheres that can be used as a contrast agent in ultrasound
      examinations. The microspheres are stabilized by a thin-layer of protein
      surrounding the air bubbles. As long as the microspheres were intact, the protein
      was insoluble in aqueous solutions. After disintegration of the microspheres, the
      protein could be solubilized in several solutions. The intermolecular
      interactions in the microsphere protein have been elucidated from its solubility
      properties. The microspheres were disintegrated by several detergents which also
      solubilized the protein. After pressure disintegration of the microspheres, the
      protein was solubilized immediately in urea and guanidinium chloride, and also in
      phosphate-buffered saline after incubation overnight. These results indicate that
      the protein was mainly stabilized by non-covalent forces. The solubilization in
      buffer was inhibited by a high salt concentration, suggesting that hydrophobic
      interactions were involved in stabilizing the microsphere structure. Analysis of
      the solubilized protein by gel filtration showed that the protein contained
      substantial amounts of soluble aggregates of HSA. Reduction of the disulphide
      bonds dissolved these aggregates into monomeric HSA, showing that intermolecular
      disulphide bonds were also involved in stabilization of the microspheres. The
      solubilized protein also contained less fatty acids than the soluble HSA used for
      the production of microspheres. These results show that the microsphere protein
      has the same characteristics as heat-denatured HSA.

PMID- 8297504
TI  - Folding and secretion of Saccharomyces cerevisiae carboxypeptidase Y are
      influenced by fusion with short heterologous peptides.
AB  - High levels of secreted yeast carboxypeptidase Y can be obtained in yeast by
      regulated overexpression under the control of the GAL1 promoter. Carboxypeptidase
      Y was investigated as a potential carrier for expression of heterologous
      oligopeptides. Coding sequences for two pentapeptides, Hepp (H-Asp-Ser-Asp-Pro
      Arg-OH) and a thymopentin analogue (H-Arg-Pro-Asp-Val-Tyr-OH), and an analogue of
      salmon calcitonin, were inserted into, or added on to, the coding sequence for
      carboxypeptidase Y, and the plasmids were introduced into a yeast mutant that mis
      sorts vacuolar proteins. Translation efficiency of mRNA from the expression
      plasmids encoding hybrid carboxypeptidase Y was apparently not influenced by the
      insert. However, secretion of the hybrid proteins was lower than that of wild
      type carboxypeptidase Y. A major fraction of the hybrid proteins accumulated
      intracellularly as a form characteristic for the endoplasmic reticulum. The
      results suggest that the inserted peptides influenced the secretion through the
      position and sequence effect on post-translational events. Furthermore, studies
      on folding properties indicated that the in vitro refolding capacity of the
      hybrid proteins was reduced. Thus, in the case of insertions, the transition from
      an unfolded chain to the correctly folded protein was likely to be disfavoured by
      misfolding. However, the tendency towards misfolding could be partially
      suppressed by changing the insertion site, and secretion was most effective in
      the cases of C-terminal fusions.

PMID- 8297505
TI  - Glycosylation and high-level secretion of human tumour necrosis factor-beta in
      recombinant baculovirus-infected insect cells.
AB  - Human tumour necrosis factor-beta (TNF-beta) was produced in eukaryotic cells
      using the insect baculovirus cloning and expression system. A novel insect signal
      sequence, the honey-bee (Apis mellifera) prepromelittin secretory sequence, was
      used to aid in the post-translational modifications, glycosylation and secretion
      of recombinant human TNF-beta. Human TNF-beta cDNA was cloned using the insect
      baculovirus vector pAcC4s. Expression of the human TNF-beta was regulated by the
      insect Autographa californica nuclear-polyhedrosis-virus polyhedrin promoter. The
      5' end of the TNF-beta cDNA was fused to the honey-bee prepromelittin signal
      sequence on the baculovirus vector. Insect [Spodoptera frugiperda (Sf9)] cells
      infected with the recombinant baculovirus secreted high levels of recombinant
      human TNF-beta into the culture medium. The amount of TNF-beta secreted by the
      Sf9 cells was estimated to be 28 micrograms of TNF-beta/ml of culture medium at
      60-72 h post infection. The secreted human TNF-beta was a 22.5 kDa polypeptide
      which was glycosylated. Amino acid sequencing of the N-terminus of the
      recombinant human TNF-beta purified from the infected Sf9-cell culture confirmed
      that the secreted product was indeed human TNF-beta. This demonstrates that the
      honey-bee prepromelittin signal sequence was efficiently recognized and
      accurately cleaved in the Sf9 insect cells. The insect-derived TNF-beta exhibited
      a high cytotoxic activity similar to that of the native human TNF-beta when
      assessed by cytotoxic assays using murine L929 cells. Thus the insect baculovirus
      expression vector can be used for the production of abundant quantities of
      biologically active, glycosylated human TNF-beta protein.

PMID- 8297506
TI  - Effects of 1,5-anhydro-D-fructose on selected glucose-metabolizing enzymes.
AB  - It was verified, by n.m.r. and fast-atom-bombardment-m.s. studies, that the C-2
      position of 1,5-anhydro-D-fructose, which was prepared by the reaction of
      immobilized glucose 2-oxidase from Coriolus versicolor (with 1,5-anhydro-D
      glucitol), is hydrated to the acetal form in water. The effects of 1,5-anhydro-D
      fructose on several glucose-metabolizing enzymes were compared with those of 1,5
      anhydro-D-glucitol. Glucose 1-oxidase from Aspergillus niger was inhibited by 1,5
      anhydro-D-fructose (Ki 6.6 mM) more effectively than 1,5-anhydro-D-glucitol (Ki
      82.5 mM). Yeast and rat brain hexokinases phosphorylated 1,5-anhydro-D-fructose
      (Km,yeast 2.3 mM: Km,rat 0.79 mM) and 1,5-anhydro-D-glucitol (Km,yeast 3.9 mM;
      Km,rat 0.83 mM). The phosphorylated forms of these compounds inhibited D-glucose
      phosphorylation by yeast hexokinase (Ki of phosphorylated 1,5-anhydro-D-fructose
      0.11 mM; Ki of phosphorylated 1,5-anhydro-D-glucitol 0.38 mM) and rat brain
      hexokinase (Ki of phosphorylated 1,5-anhydro-D-fructose 0.07 mM; Ki of
      phosphorylated 1,5-anhydro-D-glucitol 0.04 mM). Glucokinase phosphorylated
      neither 1,5-anhydro-D-fructose nor 1,5-anhydro-D-glucitol, and the
      phosphorylation of D-glucose by glucokinase was inhibited by them. Mutarotase was
      slightly inhibited by 1,5-anhydro-D-fructose, as well as by 1,5-anhydro-D
      glucitol.

PMID- 8297507
TI  - Interrelated approach to optimization of biosynthesis and chemical isolation of
      biologically active substances: the production of penicillinamidase by
      Escherichia coli and peptidohydrolase by Xanthomonas sp.
AB  - The solution to the problem of optimizing conditions for the isolation of
      biologically active substances (BAS) from microbial cells should be based on
      investigations of the structural and functional characteristics of cultures.
      Models of two bacterial cultures, of Escherichia coli and a Xanthomonas species,
      producing enzymes the localization of which differ, is described. The isolation
      of membrane-bound penicillinamidase from E. coli was optimal in the
      'preautolysis' period, when the components of the cytoplasm autolysed but the
      membranes remained intact. In contrast, the isolation of the cytoplasmic enzyme
      peptidohydrolase from Xanthomonas sp. was optimal during the period when the cell
      membranes markedly changed. Thus the physiological state of the cultures and the
      localization of the BAS within the cells are important determinants for
      optimization of the isolation process. It follows that all stages of a
      technological process for the production of BAS, i.e. biosynthesis, chemical
      isolation, etc., should be interrelated for a successful outcome.

PMID- 8297508
TI  - Protein adsorption to hydrophobic Zeolite Y: salt effects and application to
      protein fractionation.
AB  - The binding equilibria of proteins with a hydrophobic variety of crystalline
      Zeolite Y is affected by salt and is a function of the type of salt and its
      concentration. The behaviour does not always follow the conventional pattern of
      increased binding at high salt concentrations and varies also for the different
      proteins involved. The overall process may be looked upon as a salting-in/salting
      out mechanism. This material can be used as a surface for the selective
      adsorption of proteins and has been applied for the fractionation of ox heart
      homogenate in multi-stage operations. The presence of NaCl influences the protein
      binding, and this can be seen by monitoring the activity profile of lactate
      dehydrogenase. The bound protein can be reversed by treating the equilibrium
      mixture with low-molecular-mass poly(ethylene glycol)s.

PMID- 8297509
TI  - Purification of endo-polygalacturonase by affinity precipitation using alginate.
AB  - The precipitation of alginate by Ca2+ at pH 3.8 was found to occur concomitantly
      with the precipitation of endo-polygalacturonase from Aspergillus niger. Under
      optimum conditions, 92% of the enzyme activity was precipitated. The enzyme could
      be recovered from the precipitate by washing with 0.5 M NaCl/0.2 M Ca2+. All the
      precipitated endo-polygalacturonase activity could be recovered in this way. The
      enzyme thus obtained was purified 10-fold. A comparison of SDS/PAGE gel patterns
      of the crude preparation and enzyme purified by the affinity precipitation also
      showed a significant purification of the enzyme.

PMID- 8297510
TI  - The influence of pluronics and their conjugates with proteins on the rate of
      oxygen consumption by liver mitochondria and thymus lymphocytes.
AB  - The membranotropic properties of block co-polymers and their protein conjugates
      were studied by their effect on the rate of oxygen consumption by isolated liver
      mitochondria and on thymus-derived lymphocytes. The block co-polymers consisted
      of poly(ethylene oxide) (PoE) [poly(ethylene glycol)] and poly(propylene oxide)
      (PoP) to give either PoE-PoP or PoE-PoP-PoE. Both types inhibited uncoupled
      respiration of liver mitochondria in a medium containing glutamate and malate and
      also of lymphocytes. They also uncoupled respiration in the presence of succinate
      in K(+)-containing medium and of lymphocytes. A method is described for linking
      protein to the block polymers to form conjugates. Such conjugates were formed
      from alpha-chymotrypsin, BSA and cytochrome c, all of which produced similar
      effects on the respiration of the isolated mitochondria and lymphocytes. The data
      suggest that both the block co-polymers and their protein conjugates inhibit the
      NADH dehydrogenase complex and induce a K(+)-conductivity of the mitochondrial
      inner membrane; the surface activity of the conjugates allows them to pass
      through the plasma membrane and interact with the mitochondrial inner membrane.

PMID- 8297511
TI  - Large-scale immunoaffinity purification of recombinant soluble human antigen CD4
      from Escherichia coli cells.
AB  - A large-scale immunoaffinity (IA) purification process was developed for the
      isolation of recombinant soluble antigen CD4 (sCD4) from Escherichia coli
      fermentations. The monoclonal antibody used for IA purification of sCD4
      recognized a conformation-dependent epitope on the surface of domain 1 of CD4. IA
      chromatography was used to purify both sCD4-183, consisting of the N-terminal 183
      amino acids of human CD4, and sCD4-PE40, a fusion protein consisting of the N
      terminal 178 amino acids of CD4 and amino acids 1-3 and 253-613 of Pseudomonas
      exotoxin A (PE40). sCD4-183 was purified from E. coli cell pellets using cell
      disruption, protein solubilization, oxidation, Q-Sepharose anion-exchange and IA
      chromatography steps. sCD4-PE40 was purified from cell pellets using cell
      disruption, protein solubilization, oxidation, Cu(2+)-immobilized metal-affinity
      chromatography, anion-exchange and IA chromatography steps. The IA-purified sCD4
      analogues demonstrated the correct apparent molecular masses on SDS/PAGE. The
      immobilized monoclonal antibody appeared to select for correctly folded CD4
      protein, since sCD4-183 and sCD4-PE40 purified by the IA method bound human
      immunodeficiency-virus glycoprotein gp120 (HIV gp120) in vitro. sCD4-PE40
      purified by IA chromatography also inhibited protein synthesis in CV-1 cells
      expressing HIV gp120/160 at the cell surface. Relatively high recoveries of sCD4
      183 and sCD4-PE40 were observed in the IA step of the purification process (71
      and 79% recovery respectively). The results demonstrate that immobilized
      monoclonal antibodies directed against conformational epitopes may be used for
      rapid purification of gram amounts of correctly folded protein from mixtures of
      oxidized E. coli proteins.

PMID- 8297512
TI  - Characterization of proteinase A glycoforms from recombinant Saccharomyces
      cerevisiae.
AB  - Proteinase A produced by Saccharomyces cerevisiae carrying the gene PEP4 (which
      encodes the prepro-proteinase A on multicopy plasmids) was isolated and
      characterized by means of SDS/PAGE, laser desorption m.s. (l.d.m.s.) and high
      performance capillary electrophoresis. Although proteinase A is normally located
      in the yeast vacuole, overexpression resulted in it being secreted. SDS/PAGE
      revealed that the product isolated from the culture medium comprised an approx,
      7:3 mixture of two different forms of proteinase A, the apparent molecular masses
      of which were 42 and 40 kDa respectively. The exact mass of each form, measured
      by l.d.m.s., was 40,755 and 38,132 Da respectively. Further analysis employing N
      glycosidase F digestion and CNBr cleavage revealed that the larger molecule was
      native proteinase A bearing carbohydrate moieties at Asn68 and Asn269, whereas
      the smaller molecule was a proteinase A variant glycoform lacking the
      carbohydrate moiety at Asn269. Capillary electrophoresis of both the normal and
      underglycosylated proteinase A glycoforms revealed charge heterogeneities
      attributable to differences in the phosphorylation level of the carbohydrate
      moiety at Asn68.

PMID- 8297513
TI  - Characterization of natural and recombinant nuclease isoforms by electrospray
      mass spectrometry.
AB  - Isoforms of natural and recombinant nuclease have been characterized on the basis
      of their M(r) as determined by electrospray m.s.. The natural nuclease was
      isolated and purified from Serratia marcescens B10M1 and the recombinant nuclease
      from Escherichia coli MT102 carrying the plasmid p403-SD2. The primary structure
      of each of the isoforms isolated from the nuclease preparations was established
      by comparing their mass with the known amino acid sequence derived from the
      nucleotide sequence of the nuc gene. All the preparations were found to be
      contaminated with the same N-terminal split variants of native nuclease, although
      the natural nuclease contained much larger amounts of these isoforms than did the
      recombinant nuclease. The structure of some of the isoforms could be verified by
      N-terminal sequencing, and nearly all of them by isoelectric focusing.

PMID- 8297514
TI  - Immobilization and stabilization of invertase using specific polyclonal
      antibodies.
AB  - Antisera raised in rabbits to baker's-yeast invertase significantly activated the
      enzyme in vitro. The antisera contained precipitating antibodies, a significant
      fraction of which appeared to be directed against the glycosyl residues of the
      enzyme. Invertase could be immobilized as insoluble enzyme antibody adducts or by
      binding to a Sepharose matrix precoupled with the gamma-globulin fraction derived
      from the antisera. The immobilized invertase preparations exhibited high enzyme
      activity and had markedly enhanced thermal stability, which could be further
      improved by cross-linking with glutaraldehyde.

PMID- 8297515
TI  - Comparative studies on thermophilicity and thermostability of aspartate
      aminotransferases.
AB  - Aspartate aminotransferase from Sulfolobus solfataricus (AspATSs) is an extremely
      thermophilic and thermostable enzyme. In order to investigate the structural
      features which underlie thermophilicity and thermostability, two isoforms of
      AspATSs differing by a single amino acid residue were compared. The first isoform
      is the naturally occurring enzyme, whereas the second is a genetically engineered
      mutant. Thermophilicity, short-term and long-term thermostability of the
      isoenzymes were independently evaluated and the influence of a cysteine residue
      on the three properties was assessed.

PMID- 8297516
TI  - Atopic allergy and other hypersensitivities.

PMID- 8297517
TI  - The environment strikes back.

PMID- 8297518
TI  - Promotion and prevention of autoimmunity by B lymphocytes.
AB  - B lymphocytes are normally subject to heavy and ongoing selection through their
      antigen-specific Ig receptors. Self tolerance mediated through antigen-receptor
      crosslinking on B cells appears to function in a variety of different and perhaps
      complementary ways, leading to cell death or editing of the antigen-receptor
      genes. The consequences of defects in these processes are unclear, but may be
      sufficient to explain systemic autoimmune disease.

PMID- 8297519
TI  - T-cell tolerance.
AB  - As the consequences of autoimmunity are so damaging to an individual, both
      deletional and non-deletional forms of T-cell tolerance are observed in the
      thymus as well as the periphery. Although the relationship between these types of
      tolerance is not clear, recent studies in vivo and in vitro have begun to
      identify the cellular and molecular interactions involved. Whereas thymic
      development must account for both positive and negative selection, it is now
      apparent that T-cell responses in the periphery must also strike a balance
      between the generation of effector function and activation-induced tolerance.

PMID- 8297520
TI  - MHC genes in autoimmunity.
AB  - In the last year progress has been made towards elucidating the roles of the MHC
      gene products in autoimmunity. A major advance has been the recent determination
      of the crystallographic structure of the human MHC class II molecule, which will
      be invaluable in delineating the minimum structural requirements for peptides
      that induce autoimmune disease. In addition, the use of animal models and
      transgenic mouse technology is continuing to increase our understanding of the
      involvement of the MHC gene products in immunopathogenesis.

PMID- 8297521
TI  - Non-MHC-linked genes in autoimmune diseases.
AB  - Single-locus mutations in mice associated with autoimmune manifestations or
      influencing them, including lpr, motheaten and xid have been characterized at the
      molecular level. Mutations have been described in the genes encoding Fc gamma RI,
      interleukin-2 and natural resistance associated macrophage protein, which are all
      candidate genes for susceptibility loci associated with autoimmune diabetes in
      non-obese diabetic mice. Twelve regions of DNA that are associated with disease
      susceptibility have now been identified in this polygenic model of autoimmunity.
      In human autoimmune diseases, the region of DNA surrounding the insulin gene that
      is associated with susceptibility to insulin dependent diabetes mellitus has been
      narrowed down to 4.1 kilobases.

PMID- 8297522
TI  - Transgenes and knock-outs in autoimmunity.
AB  - While there have not been any earth-shattering events during the past year
      relating to the use of germline manipulation in the study of autoimmunity,
      several new developments have brought interesting insights into the way the
      immune system deals (or fails to deal) with autoantigens. Several systems
      described recently have the potential to help us understand what makes an
      autoantigen, and what events lead to a pathogenic reaction.

PMID- 8297523
TI  - T-cell autoimmunity in type 1 diabetes mellitus.
AB  - Insulin dependent diabetes mellitus is a T-cell mediated autoimmune disease.
      Several beta-cell antigens, mostly non-tissue-specific, have been implicated in
      the disease process. The antigens and the autoimmune T cells exist in healthy
      individuals, as do many of the genes required for the development of diabetes.
      The question, then, is why and how exposure to undefined environmental agents
      activates an existing autoimmune potential and directs it to damage the beta
      cells.

PMID- 8297524
TI  - Myasthenia gravis.
AB  - The cause of the myasthenics' pathogenic autoantibody response against the muscle
      acetylcholine receptor is an intriguing puzzle involving the thymus and its
      epithelial tumours, and possibly a variety of cross-reacting epitopes. Another
      fascinating challenge is to find ways of selectively inhibiting this response in
      the patients.

PMID- 8297525
TI  - Cellular immune mechanisms in rheumatoid arthritis and other inflammatory
      arthritides.
AB  - Advances in molecular genetics, cellular immunology and microbiology have offered
      promise in unravelling the aetiopathogenesis of inflammatory arthritides such as
      rheumatoid arthritis and reactive arthritis. Such insights are challenging the
      orthodox view that these diseases are primarily autoimmune in nature, and should
      lead to exciting and novel therapeutic approaches.

PMID- 8297526
TI  - Immunotherapy of autoimmune disease.
AB  - T-cell recognition of autoantigens stands as the primary target for immune
      intervention in autoimmune disease. Experiments in animal models, in combination
      with a number of clinical trials completed in the last year, have helped to
      clarify the pathogenesis of various autoimmune diseases and indicate future
      strategies for immunotherapy.

PMID- 8297527
TI  - Development of human mast cells from their progenitors.
AB  - Two types of human mast cells, which are morphologically similar to skin mast
      cells and lung mast cells, respectively, can be developed from pluripotent stem
      cells under different culture conditions. The major growth factor for mast-cell
      development is c-kit ligand, which induces mastocytosis in vivo. However, this
      cytokine is not sufficient for full maturation of the cells.

PMID- 8297528
TI  - Receptors for IgE.
AB  - Following advances during the past 5 years in our understanding of the molecular
      structure of receptors for IgE, progress has been made in elucidating the
      structure and function of IgE receptors and the signalling events through these
      receptors. IgE is not the only ligand for some of these receptors, leading to
      their having unexpected and interesting biological activities.

PMID- 8297529
TI  - The late-phase reaction: role of IgE, its receptor and cytokines.
AB  - Late phase IgE-mediated reactions (LPR) likely play a major role in the
      pathogenesis of chronic allergic diseases. Although a number of cellular and
      humoral alterations in LPR sites have been described recently, the pathogenesis
      of the LPR is still unclear. LPR follow IgE-mediated but not opiate-induced mast
      cell activation suggesting different patterns of mast cell mediator release
      and/or additional effects of the antigen-IgE interaction. Granulocyte
      accumulation in developing LPR is accompanied by altered expression of adhesion
      molecules on local vascular endothelium. Lymphocytes and the cytokines they
      produce play an important role in developing and perpetuating LPR. These findings
      point to the likely complex pathogenesis of LPR with implications for the therapy
      of allergic diseases.

PMID- 8297531
TI  - Autoimmunity.

PMID- 8297530
TI  - Role of IgE in atopic dermatitis.
AB  - Atopic dermatitis is a chronic inflammatory skin disease associated with elevated
      serum IgE levels and sensitization to a variety of inhalant, food and microbial
      allergens. Controlled challenges have provided substantial evidence that
      allergens can trigger acute IgE-mediated mast-cell dependent exacerbations of
      eczema in these patients. However, the sustained chronic skin inflammation that
      characterizes atopic dermatitis is likely to result from a local expansion of
      allergen-specific T helper type 2 cells that produce interleukin-4 and
      interleukin-5 and the concomitant infiltration of eosinophils. An important role
      for IgE in allergen presentation to T helper type 2 cells by Langerhans cells has
      been proposed. These observations may have important implications for the
      development of new approaches for the treatment of this increasingly common
      allergic disorder.

PMID- 8297532
TI  - Structure of a citrate double salt: potassium dihydrogen citrate-lithium
      potassium hydrogen citrate monohydrate.
AB  - The crystal structure of a double salt of potassium dihydrogen citrate and
      lithium potassium hydrogen citrate monohydrate has been determined. One potassium
      ion is coordinated with eight O atoms and the other with nine O atoms at M--O
      distances in the range 2.660 (1) to 3.139 (1) A. Two of these O atoms are shared
      by both potassium ions. The lithium ion is tetrahedrally surrounded by four O
      atoms at distances in the range 1.870 (3) to 1.988 (3) A. This crystal structure
      contains nine hydrogen bonds in the asymmetric unit. The water molecule connects
      different citrate ions along the c direction by hydrogen bonding.

PMID- 8297533
TI  - Structure of dipotassium hydrogen citrate.
AB  - Dipotassium hydrogen 2-hydroxy-1,2,3-propanetricarboxylate is shown by this
      crystal structure determination to be ionized at the central carboxyl group and
      one terminal carboxyl group. Each citrate ion forms an intramolecular hydrogen
      bond as well as an intermolecular hydrogen bond connecting it to an adjacent
      citrate ion. Each K ion is surrounded by eight O atoms from several citrate ions.
      The metal-oxygen distances range from 2.706 to 3.136 A.

PMID- 8297534
TI  - Structure of strontium citrate pentahydrate.
AB  - The crystal structure of tristrontium bis(2-hydroxy-1,2,3-propanetricarboxylate)
      pentahydrate has been determined. One Sr ion is coordinated with eight O atoms,
      another with nine and the third with ten at distances ranging from 2.498 (2) to
      2.781 (2) A. Two Sr ions are bound to citrate ions in a tridentate manner. Both
      citrate ions in the asymmetric unit are in an extended conformation. There are 11
      hydrogen bonds in one asymmetric unit of the crystal structure.

PMID- 8297535
TI  - Structure of 6-fluoro-1,2,3,4,7,12-hexahydro-7-methyl-12-methylene-
      benz[a]anthracene.
AB  - The X-ray analysis confirms the structure of the 12-methylene tautomer formed by
      the acid catalysis of 6-fluoro-1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene.
      The central C ring is in a boat conformation, with the result that the molecule
      is bent about a line through atoms C(7) and C(12) with a dihedral angle of 32.5
      degrees. The cyclohexene A ring is in a half-chair conformation.

PMID- 8297536
TI  - Hypertension and hyperlipidemia. A review.
AB  - In a recent meta-analysis of 13 studies of antihypertensive treatment, it was
      demonstrated that the reduction of risk for coronary artery disease was 14%
      compared with the 20% to 25% expected for a diastolic blood pressure reduction of
      5 to 6 mm Hg according to observational studies. In contrast, the obtained effect
      on stroke reduction was of the same order as that expected for a given blood
      pressure reduction. A meta-analysis of 22 lipid-lowering studies indicated a
      reduction in risk of coronary artery disease that is consistent with
      epidemiologic observations, indicating a difference in risk of 20% to 30% for a
      10% difference in cholesterol concentration. Many cross-sectional studies have
      demonstrated that hypertensive men and women are metabolically different from
      normotensive subjects. These differences include a disturbed glucose metabolism
      due to insulin resistance that may also be the basis of the observed lipid
      abnormalities and even of the hypertension itself. Some of the drugs used in the
      treatment of hypertension produce changes in metabolism such that insulin
      resistance becomes worse and lipid abnormalities become still more pronounced. In
      the case of treatment with beta-blockers, there is a change in lipoprotein
      composition that may indicate an increased tendency toward oxidation, which may
      render the lipoproteins more atherogenic. It is obvious that the metabolic
      profile in hypertensive patients warrants consideration and, furthermore, that
      the metabolic effects of different drugs should be taken into account when
      starting treatment.

PMID- 8297537
TI  - Coronary artery disease prediction.
AB  - The factors age, gender, cigarette-smoking, blood cholesterol, high-density
      lipoprotein (HDL) cholesterol, blood pressure, left ventricular hypertrophy, and
      diabetes mellitus have been used in the Framingham Heart Study for the prediction
      of coronary artery disease (CAD) in a middle-aged cohort of 2590 women and 2983
      men aged 30 to 74 years at baseline. During 12 years of follow-up, there were 385
      cases of CAD among men (12-year incidence of 5% at ages 30 to 39, rising to 26%
      at ages 70 to 74), and 241 cases among women (12-year incidence of 1% at ages 30
      to 39, rising to 20% at ages 70 to 74). This review includes examples of the
      calculation of risk factor estimates from logistic regression equation output,
      discusses the role of attributable risk, provides information concerning the
      applicability of risk factor estimates to other populations, and contrasts the
      factors responsible for the occurrence of CAD with those that are important in
      other vascular diseases such as stroke.

PMID- 8297538
TI  - Cellular mechanisms of atherogenesis.
AB  - The study of vascular cell function and the interactions of endothelial cells
      (EC), smooth muscle cells (SMC), and monocyte-derived macrophages has expanded
      greatly during the past 20 years, and the resultant information has reformed our
      views on the genesis of atherosclerotic plaque. The concept of an activated or
      injured endothelium that exhibits properties distinct from healthy adult
      endothelium is now well accepted. Activated EC may exhibit proatherogenic
      behavior, including increased leukocyte adhesivity, procoagulant activity, and
      SMC mitogen production. Thrombin, a coagulation-system protease, may serve as a
      physiologic activator of EC. Thrombin at sites of vascular injury may stimulate
      diverse functions, including increased expression of monocyte adhesion proteins
      and platelet-derived growth factor (PDGF). The monocyte-derived macrophage has
      been implicated as a participant in several aspects of atherosclerotic plaque
      development. The attachment of monocytes to EC is the initial event in the
      interaction of these cells with the vessel wall. Distinctly focal adhesion of
      monocytes to EC of large vessels is one of the earliest documented events in
      experimentally induced atherosclerosis and, thus, regulation of this process may
      be critical to the development of the disease. Intimal proliferation of SMC is
      another hallmark of the atherosclerotic lesion. Platelet-derived growth factor is
      both a chemoattractant and mitogen for SMC. Therefore, if EC secrete PDGF
      abluminally, both the migration of SMC into the intima and subsequent
      proliferation will be stimulated. Immunocytochemistry and insitu hybridization
      have verified that vascular EC express PDGF mRNA and protein in vivo under
      certain conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297539
TI  - Genetic basis of familial dyslipidemia and hypertension: 15-year results from
      Utah.
AB  - The genetic and environmental determinants of hypertension, lipid abnormalities,
      and coronary artery disease (CAD) have been studied for 15 years in Utah in
      population-based multigenerational pedigrees (2500 subjects among 98 pedigrees),
      twin pairs (74 monozygous and 78 dizygous), hypertensive siblings (131 sibships),
      siblings with CAD before age 55 (45 sibships), and anecdotally ascertained
      pedigrees with type II diabetes (271 subjects among 16 pedigrees), lipoprotein
      lipase deficiency (106 subjects in a single pedigree), and familial
      hypercholesterolemia (502 heterozygotes among 50 pedigrees). Estimates of
      heritability ranged from 20 to 75% for blood pressures and blood lipids. A strong
      positive family history predicts a future occurrence of hypertension (relative
      risk [RR] = 3.8) and CAD (RR = 12.7). Segregating single-gene effects were found
      for several 'intermediate phenotypes' associated with hypertension (erythrocyte
      sodium-lithium countertransport, intraerythrocytic sodium, a relative fat
      pattern, total urinary kallikrein excretion, and fasting insulin levels). Strong
      single-gene effects in segregation analysis were also found for low-density
      lipoprotein (LDL) cholesterol, lipoprotein (a) (Lp[a]), low high-density
      lipoprotein (HDL) cholesterol, and high apolipoprotein (apo) B. Deoxyribonucleic
      acid (DNA) markers of lipid abnormalities or hypertension have included LDL
      receptor defects, lipoprotein lipase deficiency, high Lp(a), familial defective
      apo B, decreased quantitative levels of apo B, apo E phenotype, angiotensinogen,
      and 'glucocorticoid remediable aldosteronism (GRA) hypertension.' Also tested in
      Utah studies, but not found to be DNA markers for hypertension, were the genetic
      loci for the structural genes for renin and angiotensin-converting enzyme, and
      the sodium antiport system. In addition, important gene-gene interactions (LDL
      receptor with apo E2) and gene-environment interactions (kallikrein with
      potassium intake) were found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297540
TI  - Inflammatory mechanisms of atheroma formation. Influence of fluid mechanics and
      lipid-derived inflammatory mediators.
AB  - It has been suggested that atheroma formation is a chronic inflammatory response
      to lipid-derived inflammatory mediators accumulating at selected arterial sites.
      At large artery flow dividers and curvatures, secondary flow phenomena create
      zones of stagnation and recirculation that deprive endothelial cells of shear
      stress-induced differentiation. Endothelial cell phenotypes at these sites appear
      to represent activated cells expressing membrane-associated and secreted
      molecules that favor constriction, permeability, leukocyte adhesion, thrombosis,
      and proliferation. Altered endothelial synthetic activities include an increased
      production of matrix proteins that may underlie intimal thickening at flow
      dividers and curvatures. In the presence of hyperlipoproteinemia, endothelial
      hyperpermeability, as determined by flow mechanics, and accumulation of
      subendothelial matrix proteins may favor intimal uptake and retention of low
      density lipoprotein (LDL). Local oxidative degradation of trapped LDL may
      generate lipid-derived inflammatory mediators, such as oxysterols, peroxidized
      fatty acids, and lysophospholipids. Proinflammatory properties of the latter can
      explain some of the effects that are necessary for generating atherogenic
      mononuclear (monocytic/T-lymphocytic) inflammatory responses in arterial walls.

PMID- 8297541
TI  - Magnetic resonance imaging of atherosclerotic vascular disease.
AB  - Atherosclerosis is a chronic, progressive, and often widespread arterial disorder
      in which the morphology and composition of the arterial segments containing
      atheroma are of considerable importance. Magnetic resonance imaging (MRI) allows
      non-invasive assessment of early arterial disease without the use of ionizing
      radiation. Arterial compliance, flow-wave velocity, and the pattern of flow
      within the aorta may all be disturbed by the disease, but these parameters are
      all accessible to MRI. In addition, atheroma can be directly imaged. Thus, MRI is
      valuable not only in the detection of disease, but also in the study of its
      natural history and the effects of interventions such as the control of risk
      factors and the use of lipid-lowering agents.

PMID- 8297542
TI  - Efficacy and safety of fluvastatin in hypertensive patients. An analysis of a
      clinical trial database.
AB  - The concurrence of hypertension and hypercholesterolemia leads to the clinical
      need to lower lipids in hypertensive patients. Thus, it is interesting to
      evaluate the efficacy and safety of fluvastatin, a new 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA)-reductase inhibitor, in such a patient population. A
      retrospective analysis of the clinical efficacy and safety of fluvastatin was
      based on the data from 1815 patients who received fluvastatin at daily doses of >
      or = 20 mg compared with 783 patients taking placebo. The results showed that 332
      (18.3%) of the fluvastatin-treated and 124 (15.8%) of the placebo-treated
      patients were identified as having hypertension. The percentage change from
      baseline of low-density lipoprotein cholesterol (LDL-C) in hypertensive patients
      taking fluvastatin at doses of 20 and 40 mg/day was -20% and -26%, respectively
      (placebo: 1.4%), and did not differ from the response in non-hypertensive
      patients. Increases in high-density lipoprotein cholesterol (HDL-C) as well as
      decreases in triglycerides with fluvastatin were not consistently different
      between hypertensive and non-hypertensive patients. Irrespective of the presence
      or absence of hypertension, confirmed (measured on two consecutive occasions)
      increases > three times the upper limit of normal in aspartate aminotransferase
      (ASAT) and alanine aminotransferase (ALAT) were observed in three (0.2%) and 12
      (0.7%) patients, respectively. With placebo, ALAT was increased in two patients
      (0.2%). The incidence of notable increases more than 10 times the upper limit of
      normal in creatine kinase was similar with fluvastatin compared with placebo
      (0.3% in both).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297543
TI  - Lipiduria in renal disease.
AB  - This article reviews the published data on lipiduria in both health and disease.
      Small amounts of lipid appear in the urine under normal circumstances but, in the
      nephrotic syndrome in humans, there is also a considerable amount of high-density
      lipoprotein in the urine as well as smaller amounts of other lipoproteins.
      Potential tubular re-uptake mechanisms for lipoproteins have been demonstrated in
      both animal and cell-culture models. In humans, there is no direct evidence for
      these specific re-uptake mechanisms--it is only through specific staining of
      renal biopsies for apolipoproteins that the presence of such mechanisms in
      intracellular vesicular structures is suggested. It is possible that lipoprotein
      filtration and re-uptake by the tubule are important mechanisms in tubular
      injury.

PMID- 8297544
TI  - Role of lipoproteins in progressive renal disease.
AB  - Renal diseases are often associated with hyperlipoproteinemia and
      dyslipoproteinemia. Total serum cholesterol and triglycerides are increased in
      nephrotic syndrome regardless of etiology. Approximately 40 to 50% of patients
      with renal insufficiency requiring hemodialysis show hypertriglyceridemia and
      dyslipoproteinemia. During chronic hemodialysis, high doses of unfractionated
      heparin deplete post-heparin lipolytic activity and aggravate dyslipoproteinemia.
      Hypercholestrolemia and hyperlipoproteinemia are often encountered in patients
      taking glucocorticoids and cyclosporin A after renal transplantation.
      Observations in experimental animals and in patients with genetically determined
      and acquired hyperlipidemias suggest that lipids can damage the kidney and lead
      to glomerulosclerosis. In vitro cell-culture studies of human glomerular cells
      have been useful in providing information on lipid-induced glomerular damage.
      Thus, there are strong indications that lipoproteins may play a critical role in
      the development of mesangial cell damage and progressive renal disease.
      Therapeutic measures that reduce and correct dyslipoproteinemia in renal disease
      may have long-term beneficial effects on the amelioration of renal disease.

PMID- 8297545
TI  - Coronary artery disease in diabetic patients with nephropathy.
AB  - Patients with juvenile-onset, insulin-dependent diabetes mellitus (IDDM) are at
      high risk of premature coronary artery disease. The risk is concentrated in
      diabetic patients who develop nephropathy. Synergy in atherogenesis is likely to
      be present between hyperglycemia and the metabolic alterations of diabetic
      nephropathy, which include hypertension, hypercholesterolemia, and high
      lipoprotein (a) levels. The accumulation of advanced glycation end-products in
      blood vessel walls and on lipoproteins may result in increased vascular
      permeability and uptake of cholesterol, particularly in the setting of
      hypertension and hypercholesterolemia. The net result may be acceleration of
      atherogenesis.

PMID- 8297547
TI  - Epidemiology of heart failure.
AB  - As a common sequelae of many forms of cardiovascular disease, heart failure is a
      major health problem in the United States. With recent advances in the prevention
      and treatment of cardiovascular diseases, more people are being saved from
      premature death. As a consequence, however, heart failure is likely to become
      even more widespread. This article reviews the incidence, prevalence, risk
      factors, and mortality of this very common and often lethal condition.

PMID- 8297546
TI  - Pharmacokinetics of fluvastatin and specific drug interactions.
AB  - Fluvastatin sodium (Lescol) is the first synthetic 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA)-reductase inhibitor to be studied extensively in humans.
      Absorption of fluvastatin is complete and unaffected by the presence of food.
      Systemic exposure is limited because of extensive sequestration by the liver
      and/or first-pass metabolism, a plasma half-life of approximately 30 min, no
      circulating active metabolites, and no accumulation of drug during chronic
      dosing. Approximately 95% of a single dose of fluvastatin is excreted via the
      biliary route with less than 2% as the parent compound. Studies investigating the
      effect of food on fluvastatin pharmacokinetics have demonstrated marked
      reductions in the rate of bioavailability (Cmax) of 40% to 60%. A comparison of
      drug administration with the evening meal or at bedtime revealed no significant
      differences in either the extent of bioavailability (area under the curve; AUC)
      or pharmacodynamic effect [reduction in low-density lipoprotein cholesterol (LDL
      C)]. Relative to the general population, plasma fluvastatin concentrations do not
      vary as a function of either age or gender. Administration of a single 40-mg dose
      to a patient population with hepatic insufficiency resulted in a 2.5-fold
      increase in both AUC and Cmax. Drug interaction studies with fluvastatin and
      cholestyramine (CME) demonstrated a lower rate and extent of fluvastatin
      bioavailability; no impact on efficacy was demonstrated when CME was given 4 h
      before fluvastatin dosing in clinical trials. Interaction studies with niacin and
      propranolol demonstrated no effects on fluvastatin plasma levels, and fluvastatin
      administered to a patient population chronically receiving digoxin had no effect
      on the AUC of digoxin compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297548
TI  - Medical management of chronic heart failure: direct-acting vasodilators and
      diuretic agents.
AB  - Chronic heart failure (CHF) is a clinical syndrome characterized by left
      ventricular dysfunction secondary to the loss of functional cardiac contractile
      cells following some type of myocardial damage. In response to this cell loss,
      several hemodynamic and neurohormonal compensatory mechanisms are activated,
      which can become deleterious over time. Direct-acting vasodilators, however, can
      produce favorable hemodynamic effects in this setting by reducing ventricular
      wall stress. Furthermore, diuretics can promote the excretion of sodium and
      water, thereby relieving hypervolemia and circulatory congestion. This article
      examines the role of these two classes of agents in the pharmacologic management
      of CHF.

PMID- 8297549
TI  - Pharmacologic management of heart failure: positive inotropic agents.
AB  - The use of positive inotropic agents in the acute and chronic treatment of heart
      failure is associated with a variety of hemodynamic effects. The beneficial
      effects of these agents, however, are not without associated adverse effects. An
      increase in cardiac output is achieved through diverse pharmacologic mechanisms
      of action depending on the specific inotropic agent. Digitalis glycosides, beta
      adrenergic agonists, and phosphodiesterase inhibitors are described.

PMID- 8297550
TI  - Sudden cardiac death in patients with heart failure.
AB  - Sudden cardiac death accounts for up to one half of the heart failure deaths each
      year. Thus, an understanding of the possible mechanisms, markers, and treatments
      of sudden cardiac death is an important component in the care of this patient
      population. This article discusses recent hypotheses as well as both preventative
      and interruptive therapies for sudden cardiac death in heart failure.

PMID- 8297551
TI  - Myocardial revascularization in the patient with severe left ventricular
      dysfunction.
AB  - In the past, poor ventricular function was considered a contraindication for
      myocardial revascularization. More recently, however, patients once considered to
      be a prohibitive risk for coronary artery bypass procedures are undergoing
      surgery with acceptable operative mortality and successful long-term outcomes. In
      fact, reparative surgical results often exceed those achieved through medical
      management and/or transplantation.

PMID- 8297552
TI  - Dynamic cardiomyoplasty and its use in patients with chronic heart failure.
AB  - Chronic heart failure is a growing problem affecting an increasing number of
      patients. Medical therapies exist, but many patients are not able to fully
      benefit from these therapies. Few surgical therapies have been effective in
      managing chronic heart failure. This article provides a comprehensive overview of
      dynamic cardiomyoplasty. This surgical therapy is a new procedure being utilized
      to enhance myocardial function in patients with end-stage heart failure. Also
      discussed are patient selection criteria, skeletal muscle transformation, and
      pulse train stimulation. The surgical procedure is described and postoperative
      nursing care guidelines are outlined. Surgical outcomes are presented.

PMID- 8297553
TI  - Transplantation in end-stage heart failure.
AB  - The benefits and limitations of cardiac transplantation as a treatment option are
      presented. Also discussed are the phases of the transplant process and pertinent
      nursing interventions. Advances in immunosuppressive drugs and patient management
      are highlighted, and long-term considerations and possible advances for the
      future are presented.

PMID- 8297554
TI  - Bridging to transplant: mechanical support for heart failure.
AB  - The success of cardiac transplantation is limited by the gap between the supply
      and demand of donor hearts. This limitation increases the risk of patient
      morbidity and mortality during the long waiting period. A variety of temporary
      support devices are in use as "bridges to transplant" to sustain cardiac function
      until a suitable organ donor is found. A device to permanently replace the
      failing heart is close to becoming a reality, as data from temporary support
      devices indicate that permanent devices are feasible. As reliability improves,
      the effectiveness of mechanical support may approach the survival rate of current
      transplant procedures. Successful permanent support may be an alternative to
      transplantation and may provide effective treatment for those patients with end
      stage heart failure.

PMID- 8297555
TI  - Quality of life in patients with chronic heart failure.
AB  - Quality of life as an outcome of medical treatment and nursing care is important
      and has received more attention by researchers during the last decade. Patients
      with heart failure generally describe a perceived poor quality of life, while
      advanced heart failure patients report improved quality of life after
      transplantation. Findings on quality of life after implantation of mechanical
      assist devices to treat heart failure are very limited. The refinement of a
      definition of quality of life and improved methods to study quality of life will
      contribute to a better understanding of this complex concept in heart failure
      patients.

PMID- 8297556
TI  - Blunt thoracic injuries.
AB  - While fewer patients with isolated blunt chest trauma are admitted to the ICU
      than in previous years, those with multisystem trauma or life-threatening
      injuries such as aortic disruption or massive lung contusion need aggressive
      nursing care. This article surveys the most widely encountered blunt thoracic
      traumas as well as difficult-to-diagnose myocardial and pulmonary injuries.
      Comprehensive trauma, thoracic assessment, and critical care therapeutics are
      discussed.

PMID- 8297557
TI  - Penetrating chest trauma.
AB  - This article reviews the current concepts in penetrating chest trauma. The
      authors discuss mechanisms of injury, nursing assessment, and interventions for
      penetrating injuries resulting in cardiac rupture, cardiac tamponade, tension
      pneumothorax, hemothorax, great vessel injury, and sucking chest wounds.

PMID- 8297558
TI  - Anesthesia in chest trauma: implications for critical care.
AB  - This article outlines some of the concerns and considerations in the anesthetic
      management of critically ill patients with chest trauma during their initial
      resuscitation and intraoperative course. The management decisions made during
      this critical period have clear implications for patient care once the patient
      arrives in the intensive care unit. It is the goal of this article to outline the
      rationale for these management decisions in order to facilitate the transfer of
      the patient from the operating room or trauma bay to the intensive care unit and
      allow the critical care nurse to establish effectively the expectations for
      postoperative recovery.

PMID- 8297559
TI  - Strategies for pain management in traumatic thoracic injuries.
AB  - Tissue damage, such as that caused by traumatic injury, is associated with the
      sensations and responses characterized initially as acute pain. It is known that
      unrelieved pain contributes to morbidity and mortality in surgical patients. Is
      pain contributing to morbidity and mortality in critically injured patients as
      well? Nurses are in a critical position to assess and manage pain. They must be
      familiar with the wide variety of available pain management techniques and be
      prepared to advocate their use.

PMID- 8297560
TI  - Adult respiratory distress syndrome following thoracic trauma.
AB  - Thoracic trauma is frequently complicated by the development of Adult Respiratory
      Distress Syndrome (ARDS). Over the past 20 years numerous articles and book
      chapter have explored the causes and clinical course of the syndrome. There still
      remains debate, however, concerning the pathophysiology and most effective
      treatment modalities. It is apparent that trauma activated numerous complex
      biochemical pathways, such as the complement and arachidonic acid cascades, which
      probably resulted in neutrophil and macrophage mediated tissue injury. This
      article examines some of the more recent thoughts about the underlying
      pathophysiology. It also outlines some of the latest treatment techniques for
      ARDS, as well as the accompanying nursing therapeutics.

PMID- 8297561
TI  - Chest trauma in the elderly.
AB  - The number of injured elderly is expected to increase over the next 20 years. The
      mortality for injured persons age 50 years and older is higher than expected at
      all levels of injury severity. No good explanation for this phenomenon exists,
      although chronic disease is frequently cited. Presently, treatment guidelines are
      derived from gerontology and a limited geriatric trauma base.

PMID- 8297562
TI  - Model for trauma outcomes management in patients with multiple trauma.
AB  - Critically injured patients with chest trauma generally sustain severe life
      threatening injuries. Post-operative care tends to be complex, and all aspects of
      care from pre-hospital through rehabilitation must be coordinated and
      communicated to maximize patient outcomes. The Trauma Outcomes Management Model
      allows clinicians to assess, track, and analyze the relationship among
      interventions, outcomes, and the cost of care for each phase of the trauma care
      continuum. This article presents the design and utilization of trauma outcome
      guides in the Emergency and Critical Care departments.

PMID- 8297563
TI  - The role of hemofiltration in the critically-ill intensive care unit patient:
      present and future.
AB  - The development of acute renal failure (ARF) in intensive care unit (ICU)
      patients carries a poor prognosis. Today, most cases are no longer an isolated
      organ dysfunction but are part of a multiple system organ failure syndrome.
      Recently developed renal replacement therapies allow adequate metabolic control,
      even in highly catabolic and hemodynamically unstable patients. Whether these
      newer continuous techniques have resulted in a better outcome of these patients
      is unclear. Recent data suggest a possible beneficial effect of hemofiltration on
      outcome of ICU patients and the course of human and experimental septic shock,
      which may be ascribed to the removal of inflammatory mediators. The purpose of
      this paper is to review the history of hemofiltration techniques and to assess
      their present and future role in the management of ICU patients. Although
      hemofiltration has been shown to improve hemodynamics of experimental septic
      shock, convincing evidence that hemofiltration improves outcome of ICU patients
      is lacking. Available data suggest that high ultrafiltrate volumes may be needed
      to achieve clinically important beneficial effects of hemofiltration in these
      patients. Prospective, randomized trials in homogeneous patient groups are needed
      to assess the role of hemofiltration in patients with septic shock or multiple
      system organ failure.

PMID- 8297564
TI  - Cardiovascular response during hemodialysis and hemofiltration: thermal,
      membrane, and catecholamine influences.
AB  - Nine patients on regular dialysis were studied, in a cross-over format comparing
      hemodialysis (HD) and hemofiltration (HF), to identify potential mechanisms of
      the disparate hemodynamic responses. Dialysis and substitution fluid composition
      (high sodium, acetate), treatment time, fluid loss rate, and membrane type (AN
      69) were matched. Cardiac output was determined by changes in thoracic electrical
      bioimpedance. Cardiac output remained stable during HF but increased during HD (p
      < 0.001, HD vs. HF), despite a parallel reduction in stroke volume. The heart
      rate response was significantly greater during HD relative to HF (p < 0.01).
      Systemic vascular resistance remained stable during HF but decreased
      significantly during HD (p < 0.05). Although there was a modest fall during HD,
      the difference in blood pressure at the end of treatment between HD and HF was
      not significant. Comparable increases in body temperature were observed during
      both treatments. Plasma catecholamines increased in parallel during HD and HF and
      following orthostatic stimulation at the end of treatment, and extracorporeal
      catecholamine clearances were similar. The values for serum sodium, total CO2,
      anion gap, potassium, and hematocrit at the end of treatment were similar,
      whereas total serum calcium was significantly greater following HD. There were no
      significant differences in indices of myocardial contractility or central blood
      volume. These results suggest that the disparate hemodynamic responses to fluid
      and solute removal during HD and HF can be dissociated from changes in osmolality
      or venous tone, membrane bioincompatibility, thermal stress, or differences in
      acetate delivery or catecholamine release. The explanation for the disparate
      hemodynamic responses between these two treatment modalities remains unclear. A
      role for an as yet unidentified vasodilatory substance generated during dialysate
      exposure, or convectively removed during hemofiltration, remain intriguing
      possibilities.

PMID- 8297565
TI  - Long-term effects of recombinant human erythropoietin on macro- and
      microcirculation in chronic hemodialysis patients.
AB  - Recombinant human erythropoietin therapy (ReHuEpo) at short term leads to an
      increase in systemic vascular resistance and to a decrease in cardiac index and
      skin microcirculatory flow. Long-term adaptive changes might occur. We studied
      the effects of ReHuEpo therapy on macrocirculation and skin microcirculation in 8
      normotensive and normovolemic hemodialysis patients before and after,
      respectively, 4 and 14 months of treatment. The reported macrocirculatory changes
      at short term were at long term not significantly different as compared with the
      initial values. The mean arterial pressure remained unaltered, as might be
      explained by the slow correction of the hematocrit and the decrease in cardiac
      output in all initially long-lasting normotensive patients who were maintained
      normovolemic. Left ventricular end-diastolic dimensions decreased, and also the
      left ventricular muscle mass decreased, depending on the initial left ventricular
      muscle mass. The skin oxygenation improved, whereas the maximal capillary flow
      decreased both at short- and long-term ReHuEpo treatment. The number of
      capillaries in the nail fold remained unchanged. However, the percentage of
      tortuosity decreased significantly during ReHuEpo therapy.

PMID- 8297566
TI  - Effect of alternative osmotic agents on peritoneal transport.
AB  - To investigate the impact of osmotic agents on solute transport in continuous
      ambulatory peritoneal dialysis single 6-hour dwell studies were performed in
      nondiabetic patients using different osmotic agents: glucose 3.86%, amino acids
      2.70, and glycerol 2.50%. Diffusive mass transport coefficient (KBD) and sieving
      coefficient (S) were assessed for urea, creatinine, glucose, glycerol, potassium,
      sodium, and total protein using the Babb-Randerson-Farrell model. The estimated
      KBD values for small solutes were higher in peritoneal dialysis fluid based on
      amino acids than in both glucose- and glycerol-based dialysis solutions. S values
      for small solutes were higher in glucose-based peritoneal dialysis fluid than in
      dialysis solutions based on amino acids and glycerol. Moreover, nonphysical,
      i.e., out of the range 0-1, S values were obtained for urea and potassium in
      glucose-based peritoneal dialysis fluid and for glucose and glycerol applied as
      osmotic agents. No difference in the transport parameters for total protein was
      found between the three investigated dialysis fluids. We conclude that the
      composition of dialysis fluid (osmotic agent, buffer solute, pH) can change the
      transport characteristics of the peritoneum. Furthermore, other physiological
      processes besides the diffusive and convective transport can contribute to the
      net peritoneal transport of some solutes.

PMID- 8297567
TI  - Sharp high-sensitivity high-temperature superconducting magnetic sensor
      successfully measures the magnetic field of the heart.

PMID- 8297568
TI  - Teleconsultation of patients with otorhinolaryngologic conditions. A
      telendoscopic pilot study.
AB  - OBJECTIVE: We have integrated endoscopic equipment with a network of video
      conference studios to develop a remote consultation service for diagnoses of
      patients with otorhinolaryngologic conditions. DESIGN: The study was performed as
      a diagnostic test in three phases. During the first phase, a general practitioner
      was instructed in otorhinolaryngologic examination techniques. In the second
      phase, remote endoscopic examinations were simulated and the diagnostic results
      were compared with results from a standard examination. In the third phase, the
      general practitioner made real telendoscopic examinations. SETTING: Signals from
      a video camera attached to the endoscope are transmitted from the primary care
      center to the otorhinolaryngologist who is 180 km away via a 2-million-bits-per
      second circuit. The specialist observes the endoscopic examination on a monitor
      and influences the control and movement of the endoscope by communicating over a
      two-way sound-and-picture connection with the general practitioner. PATIENTS: A
      convenience sample of 24 patients was examined in the last two phases. RESULTS:
      Although the video image is compressed before transmission over the
      telecommunications network, our results show that the quality of the transmitted
      images was equivalent to the quality of the images from a standard endoscopic
      examination. CONCLUSIONS: Our study has shown that this method of consultation
      may be used in the clinic with the same degree of reproducibility as in a
      conventional consultation situation. This enables us to give patients in remote
      locations better service at a lower cost.

PMID- 8297569
TI  - Fasciaform myringoplasty in children.
AB  - OBJECTIVE: To evaluate the efficacy of fasciaform myringoplasty as a means to
      repair large tympanic membrane perforations in children. DESIGN: Retrospective
      review of the records of 26 patients who underwent 29 consecutive fasciaform
      myringoplasty surgeries over a 47-month period. Patients were followed up from 2
      to 47 months postoperatively. SETTING: Academic tertiary care children's
      hospital. PARTICIPANTS: Twenty-six patients (5 to 16 years old), with tympanic
      membrane perforations (25% to 95%) underwent a fasciaform myringoplasty
      procedure. The perforations were caused by extrusion of ventilation tubes (83%),
      deep retraction pockets, trauma, or repair after resection of cholesteatoma.
      INTERVENTION: The surgery involves resection of the native tympanic membrane and
      annulus. A new tympanic membrane is formed from formaldehyde-fixed autogenous
      temporalis fascia and positioned. OUTCOME MEASURE: Successful repairs,
      complications, and audiometric evaluations were analyzed. Fisher's Exact Test was
      used to compare complication rates by age. RESULTS: Successful closure was
      accomplished in 69% of cases. Otitis media recurred in 52%. Ventilation tubes
      were reinserted in 24%; 28% resolved with antibiotics alone. When tubes were
      placed through the graft, small residual graft perforations resulted. Audiometric
      evaluation revealed improvement in pure tone average to less than a 20-dB hearing
      level in 77% and reduction of the air-bone gap to within a 20-dB hearing level in
      90% of those cases (10/29) with complete audiometric data. CONCLUSIONS:
      Fasciaform myringoplasty has proven to be a successful procedure for closing
      large tympanic defects and improving hearing acuity in the pediatric population.
      However, recurrent otitis media and eustachian tube dysfunction may continue.
      Rates of reperforation were statistically significantly higher in children 7
      years old and younger. Conservative management of children in this younger age
      group is warranted.

PMID- 8297570
TI  - The human adenoid. A morphologic study.
AB  - OBJECTIVE: We examined the route by which antigen on the surface of the adenoid
      may be brought into contact with the lymphoid follicles in the submucosa of the
      adenoid. DESIGN: We studied under light and electron microscopy 13 adenoids from
      children undergoing elective surgery. Portions of all of the specimens were fixed
      in formalin and embedded in paraffin and plastic for hematoxylin-eosin and
      periodic acid-Schiff staining. Portions of four adenoids were fixed in
      glutaraldehyde for electron microscopy. RESULTS: Two major types of epithelium
      were evident by light microscopy: a ciliated or squamous epithelium containing
      few lymphocytes and a nonciliated-flat epithelium with a heavy infiltration of
      lymphocytes ("lymphoepithelium"). Scanning microscopy showed the surface of this
      lymphoepithelium to be composed largely of cells with multiple microfolds known
      as M-cells. Freeze-fracture technique showed many lymphocytes under the M-cells.
      Transmission electron microscopy showed the lymphocytes to be located in
      compartments formed by the epithelial cells. Light microscopy study of 50 serial
      sections embedded in plastic suggested that the compartments communicated to form
      intraepithelial channels for the lymphocytes. CONCLUSION: The epithelium of the
      adenoid has areas with ciliated epithelium adjacent to areas with epithelium
      containing M-cells and intraepithelial lymphatic channels. HYPOTHESIS: The
      lymphoepithelium of the adenoid is a mechanism for transporting antigen via the M
      cells to the underlying lymphoid follicles.

PMID- 8297571
TI  - Prevalence of IgE-mediated hypersensitivity in children with adenotonsillar
      disease.
AB  - OBJECTIVE: To determine the prevalence of allergy in children with severe
      adenotonsillar disease and to determine if the persistence of symptoms following
      tonsillectomy may be related to the allergic state. DESIGN: A prospective study
      of a cohort of 108 patients. SETTING: Academic tertiary referral medical center.
      PARTICIPANTS: Consecutive children scheduled to undergo tonsillectomy for
      obstructive hypertrophy or recurrent infection were eligible to enroll in this
      study. Over a 17-month period, 108 patients enrolled. One-year follow-up data
      were obtained on 78% of patients. A group of 59 age-matched controls was used for
      comparison. INTERVENTION: Radioallergosorbent test analysis was performed on all
      study patients and controls. The study patients had the following surgical
      procedures: adenotonsillectomy in 61 cases (55%); adenotonsillectomy-myringotomy
      tubes in 31 cases (28%); tonsillectomy in 14 cases (13%); tonsillectomy-tubes in
      one case (< 1%); and adenotonsillectomy-unilateral tube in one case (< 1%).
      OUTCOME MEASURE: Detection of allergy and postsurgical outcome. RESULTS: Allergy
      was detected by radioallergosorbent test analysis in 23 (21%) of the study group
      and 12 (20%) of the control group. Fourteen patients (17%) reported obstructive
      symptoms unchanged or worse 1 year following surgery. Three of these children
      were allergic. Sixteen patients (21%) reported allergic symptoms unchanged or
      worse following surgery. Three of these children were allergic. In six patients
      (7%), asthma developed following tonsillectomy. None of these children were
      allergic. CONCLUSIONS: The prevalence of allergy in children with severe
      adenotonsillar disease is the same as that of age-matched controls. No
      relationship was detected between resolution of symptoms following tonsillectomy
      and the presence of allergy. We found no increased prevalence in the development
      of asthma following tonsillectomy in the allergic child.

PMID- 8297572
TI  - Tracheobronchomalacia in children.
AB  - Tracheobronchomalacia (TBM) is an important cause of airway distress during
      infancy, but it generally resolves as the airway enlarges. To assess the origin
      and natural history of TBM, a chart review and telephone survey were conducted
      for 50 patients with TBM at the Children's Hospital of Philadelphia (Pa). This
      study revealed that TBM is a relatively common airway abnormality and is found on
      15% of all diagnostic bronchoscopies. Prematurity, low birth weight,
      bronchopulmonary dysplasia, and prolonged ventilation predispose patients to the
      most severe symptoms. In our study, a tracheotomy with continuous positive airway
      pressure was required by 75% of the premature infants and 25% of the full-term
      infants with TBM. Seventy-one percent of all patients underwent decannulation
      without any other surgical intervention and remained nearly asymptomatic. Some
      patients could not undergo decannulation because of other airway lesions. In most
      instances, TBM is a self-limited disease that resolves without surgery.

PMID- 8297573
TI  - Neurologic sequelae secondary to atlantoaxial instability in Down syndrome.
      Implications in otolaryngologic surgery.
AB  - OBJECTIVE: A comprehensive overview of atlantoaxial instability in Down syndrome
      as it relates to head and neck surgery and recommendations as derived from a
      review of the literature. DATA SOURCES: English-language literature:
      otolaryngologic problems in Down syndrome and atlantoaxial biomechanics. DATA
      SYNTHESIS: Children affected with Down syndrome frequently require
      otolaryngologic procedures such as myringotomy with ventilation tubes or
      adenotonsillar surgery. Atlantoaxial instability occurs in 10% to 20% of patients
      with Down syndrome who are at risk for atlantoaxial subluxation and subsequent
      complications during anesthetic induction and during positioning and manipulation
      associated with surgery. To identify patients who are at risk for atlantoaxial
      subluxation, guidelines have been adapted from the recommendations of the
      American Academy of Pediatrics and the Special Olympics Inc, which include
      preoperative neurologic assessments and cervical roentgenograms in the neutral,
      flexion, and extension positions. Children with an atlantodental interval of
      greater than 4.5 mm or with peripheral neurologic findings should have further
      evaluation. CONCLUSIONS: A small percentage of patients with Down syndrome are at
      risk for atlantoaxial instability and subluxation. All patients with Down
      syndrome should have a preoperative neurologic assessment screening by the
      operating surgeon and/or a cervical roentgenogram in the lateral, extension, and
      flexion positions. Any abnormality should be investigated before surgery.

PMID- 8297574
TI  - The preauricular portion of the rhytidectomy incision.
AB  - OBJECTIVE: To evaluate the best placement of the preauricular portion of the
      rhytidectomy incision in the female patient from the aesthetic point of view.
      DESIGN: Blind, randomized review of close-up photographs of the ear area in 36
      patients after rhytidectomy. SETTING: Office surgical suite, accredited by
      Accreditation Association of Ambulatory Health Care. PARTICIPANTS: Two facial
      plastic surgeons and two plastic surgeons, all skilled rhytidectomy surgeons.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Participants received close-up
      photographs of the ear area of 36 patients at least 6 months after rhytidectomy.
      Eighteen patients had posterior tragal edge incisions and 18 patients had
      pretragal incisions. Cases were randomized. Participants were asked to rate the
      preauricular portion of the rhytidectomy incisions overall as to aesthetic
      results. The categories were excellent, good, average, acceptable, and poor.
      RESULTS: Results of surveys were collated. Three categories of results were
      determined: best, acceptable, and poorest. Posterior tragal edge incisions scored
      higher than pretragal incisions. Those incisions that scored in the best category
      tended to have a normal contour of the tragus and normal pretragal sulcus.
      Incisions that scored in the poorest category tended to have a flat posttragal
      edge with obliteration of the pretragal sulcus. CONCLUSIONS: The incision at the
      posterior edge of the tragus is preferred over the pretragal incision for female
      rhytidectomy patients except those with a large, prominent or angulated tragus.

PMID- 8297575
TI  - Transconjunctival approach to lower eyelid blepharoplasty. Experience,
      indications, and technique in 300 patients.
AB  - Despite the fact that transconjunctival approach to lower eyelid blepharoplasty
      is not a new technique, the indications, patient selection, technique, and
      results using this technique have not previously been widely reported.
      Specifically, we have compared the results of this blepharoplasty procedure in
      terms of the indications, expected results, postoperative complications, and
      patient satisfaction in 300 successive cases of skin-muscle flap approach with
      those in 300 cases in which the transconjunctival approach was used. The
      orientation and details of this approach for the facial plastic surgeon are well
      outlined. Associated adjunctive procedures such as simultaneous chemical peeling
      and the "pinch" technique for skin excess removal are discussed. Both short- and
      long-term complications are significantly reduced with the transconjunctival
      approach to lower lid blepharoplasty compared with the skin-muscle flap approach.
      Therefore, for the removal of pseudoherniation of orbital fat of the lower
      eyelid, the transconjunctival approach to lower lid blepharoplasty should have a
      significant place in the surgical armamentarium of the facial plastic surgeon.

PMID- 8297576
TI  - Intraoperative custom contouring of the mandible.
AB  - OBJECTIVE: The purpose of this study was to apply a quantitative approach to
      augmentation mentoplasty with Silastic implants to achieve consistently accurate
      results. A Silastic extension wafer was introduced for custom contouring implants
      as part of this technique. DESIGN: Case series. SETTING: Private practice.
      PATIENTS: One hundred patients undergoing elective facial cosmetic surgery. For
      the main outcome measure, ideal profile augmentation was defined as projecting
      the most anterior point of the patient's chin on profile to within 2 mm of a
      vertical line dropped from the lower lip. RESULTS: Using a quantitative approach,
      98 of 100 patients were able to achieve ideal profile augmentation. CONCLUSIONS:
      A quantitative approach to augmentation mentoplasty can provide consistently
      accurate results. Easy intraoperative customization of Silastic implants is
      necessary for this type of technique. A Silastic extension wafer is an effective
      method for intraoperative customization of implants.

PMID- 8297577
TI  - Motion observed across maxillary continuity defects stabilized with plates and
      screws.
AB  - The stability of fixation obtained with internal fixation devices (plates and
      screws) under functional loading of maxillary continuity defects was studied
      using fresh cadaver skulls. Micromotion (deformation) was recorded in the model
      across the level of the LeFort I osteotomies even when fixation was thought to be
      grossly stable. Deformation in this biologically static model proved to be mostly
      elastic in nature, and the amount of deformation in each skull appeared to be
      predictable from the average stability of all screws used in each plate. Such
      motion in viable bone could lead to permanent deformation due to resorption and
      remodeling of bone around the screws if initial overall fixation stability is
      tenuous. The results suggest that the term "rigid" is inappropriately used to
      describe plate and screw fixation of maxillary continuity defects.

PMID- 8297578
TI  - Influence of cocaine and lidocaine on human nasal cilia. Beat frequency and
      harmony in vitro.
AB  - The effects of cocaine and lidocaine on ciliary beat frequency and ciliary beat
      harmony were studied in biopsy specimens of normal human nasal mucosa. Cocaine
      was investigated in increasing concentrations (0.875%, 1.75%, 3.5%, and 7%) in
      five samples; lidocaine (0.125%, 0.25%, 0.5%, 1%, and 2%), in four samples.
      Ciliary beat was recorded photoelectrically and the signal was analyzed. Cocaine
      was found to decrease ciliary beat frequency and ciliary beat harmony at
      concentrations of 1.75% and higher. Partially reversible ciliostasis was seen at
      7%. Lidocaine was found to decrease ciliary beat frequency and ciliary beat
      harmony at concentrations of 0.25% and higher. Irreversible ciliostasis was seen
      at 2%. Cocaine and lidocaine affected ciliary beat frequency and ciliary beat
      harmony in the same way.

PMID- 8297579
TI  - Glomus tympanicum in infancy.
AB  - A glomus tympanicum tumor, limited to the cochlear promontory, was excised from
      the middle ear of a 6-month-old girl. To our knowledge, there have been no
      reports of temporal bone paragangliomas occurring at a younger age. Diagnosis,
      therapy, and the special characteristics of pediatric glomus tumors are
      discussed.

PMID- 8297580
TI  - Osteoma of the internal auditory canal. A case report.
AB  - Osteomas of the petrous temporal bone are rare and seldom symptomatic. This
      report describes an osteoma of the internal auditory canal, causing compression
      of the eighth nerve, leading to auditory and vestibular complaints. The symptoms
      were abolished by surgical decompression of the internal auditory canal and
      removal of the osteoma.

PMID- 8297581
TI  - Ablation of luteal phase symptoms of Meniere's disease with leuprolide.
AB  - Symptoms of Meniere's disease in women may be exacerbated during the luteal phase
      of the menstrual cycle. This suggests a role for progesterone production and
      subsequent fluid redistribution as a predisposing factor for Meniere's symptoms.
      We report the use of leuprolide acetate, a gonadotropin-releasing hormone
      agonist, in a woman with cyclic Meniere's symptoms. This drug, which abolishes
      gonadotropin-dependent ovarian sex steroid production, alleviated the patient's
      symptoms during therapy. This observation offers further support to the
      hypothesis of sex hormone-related exacerbations of Meniere's symptoms and
      provides a possible future treatment option for this debilitating disease.

PMID- 8297582
TI  - Cricoarytenoid arthritis and ankylosing spondylitis.
AB  - A variety of systemic diseases may manifest with laryngeal symptoms.
      Cricoarytenoid arthritis with or without limitation of vocal fold motion is an
      example. It has been described in up to 25% of rheumatoid patients. Ankylosing
      spondylitis is classified among the seronegative spondylarthritides. Besides its
      systemic features, rare reports of cricoarytenoid involvement have been
      published. Six previous cases reported have been characterized by a long history
      of ankylosing spondylitis before the cricoarytenoid joint involvement occurred.
      We describe only the seventh case of cricoarytenoid arthritis secondary to
      ankylosing spondylitis and the first patient (to our knowledge) to present with
      bilateral vocal fold fixation as the initial presenting symptom.

PMID- 8297583
TI  - Unilateral palatal adhesion for paralysis after high vagal injury.
AB  - Tumor involvement or sacrifice of the vagus nerve at the level of the jugular
      foramen is a cause of significant morbidity in skull base surgery. Management of
      the resulting dysphagia and dysphonia has been significantly improved by the
      development of vocal cord medialization. However, rehabilitation of palatal
      paralysis with the resulting velopharyngeal incompetence has not been widely
      addressed. In an effort to alleviate the symptoms of hypernasality and nasal
      reflux, unilateral adhesion of the palate to the posterior wall of the
      nasopharynx is proposed. This report summarizes the operative approach and
      results in eight patients. Results have been favourable with no significant
      postoperative complications observed to date.

PMID- 8297584
TI  - Imaging quiz case 2. Pleomorphic adenoma.

PMID- 8297585
TI  - Imaging quiz case 1. Metastatic cervical lymph nodes (LNs).

PMID- 8297586
TI  - An air quality data analysis system for interrelating effects, standards, and
      needed source reductions: Part 12. Effects on man, animals, and plants as a
      function of air pollutant impact.
AB  - The impact-effect mathematical model, developed in 1991, improves on a previous
      mathematical model, and was developed to predict biological response as a
      function of air pollutant impact. Impact is defined here as exposure duration
      multiplied by air pollutant concentration raised to an exponent (t.cd). This
      paper's purpose is to plot and regress example biological effects as a function
      of air pollutant impact to determine how well the plotted data fit the impact
      effect model for three target populations: man, animals, and plants (a wide range
      of life forms). The three biological effects are: for man, lung function decrease
      after exposure to ozone (O3); for animals, mouse mortality after exposure to
      nitrogen dioxide (NO2); and for plants, leaf injury after exposure to O3. The
      three resultant regression equations account for a substantial amount of the data
      variance: 95 percent for lung function, 92 percent for leaf injury, and 73
      percent for mouse mortality. The model fits the animal and plant data that cover
      both acute and chronic exposures. The animal exposures ranged from 6 min to 1 yr.
      The plant exposures ranged from 0.75 to 552 h.

PMID- 8297587
TI  - Glycosylation as a factor affecting product consistency.

PMID- 8297588
TI  - Protein stability: impact upon protein pharmaceuticals.

PMID- 8297589
TI  - Assessing genetic stability of a recombinant protein at the nucleic acid level.

PMID- 8297590
TI  - The use of peptide mapping for the detection of heterogeneity in recombinant DNA
      derived proteins.

PMID- 8297591
TI  - Applications of nuclear magnetic resonance, circular dichroism and fluorescence
      spectroscopy to the characterization of biological products.

PMID- 8297592
TI  - New developments in biochemical mass spectrometry.

PMID- 8297593
TI  - Cytokines--protein structure and biological activity: a complex relationship with
      implications for biological assays and standardization.

PMID- 8297594
TI  - Genetic stability: an issue of product quality.

PMID- 8297595
TI  - Genetic stability and recombinant product consistency.
AB  - A committee of U.S. industry scientists from the Pharmaceutical Manufacturers
      Association has reviewed the recent suggestions of Galibert and Center for
      Biologics Evaluation and Research (CBER) regarding assurances of product
      consistency by cloning and sequencing efforts. We disagree that their proposals
      will achieve this goal, and estimate that such efforts will be very costly in
      terms of regulatory agency time examining artifactual errors as well as industry
      resources. We feel that current analytical and manufacturing technology is
      adequate to assure recombinant product consistency without the suggested cloning
      and sequencing measures.

PMID- 8297596
TI  - Genetic stability and product consistency of rDNA derived biologicals.

PMID- 8297597
TI  - Evaluation of genetic stability.

PMID- 8297598
TI  - Genetic stability and product consistency: EC point of view.

PMID- 8297599
TI  - Determination of size of antigenic fragments after treatment of enveloped viruses
      with non-ionic detergents.
AB  - The two-dimensional double immunodiffusion, the so-called 'two-cross' method, is
      introduced for determination of the size of antigenic subunits released after
      solubilization of enveloped viruses with non-ionic detergents. The method enables
      the determination of diffusion coefficients and calculation of relative molecular
      masses of immunoreacting components without using any standard and without prior
      isolation, purification or labelling of material to be analysed. The molecular
      masses of surface antigenic fragments of the Newcastle disease virus (NDV)
      disrupted by non-ionic detergent Triton X-100 were determined. Two antigenic
      fragments, the larger having a molecular mass between 350 and 187 kDa and the
      smaller from 140 to 86 kDa, were released by the action of 0.1-1.0% detergent at
      20 degrees C. One fragment, whose molecular mass varied from 210 to 187 kDa, was
      obtained at 37 degrees C after treatment of NDV with 0.2-1.0% detergent,
      respectively The detergent disruption of purified NDV is studied for comparison.
      No difference was found whether purified or NDV in allantoic fluid was subjected
      to the same detergent extraction.

PMID- 8297600
TI  - Determination of foetal calf serum in vaccine preparations by immunoradiometric
      assay and enzyme-linked immunosorbent assay.
AB  - A simple and sensitive immunoradiometric assay (IRMA) for detection of foetal
      calf serum proteins in vaccine preparations has been developed. In this two-site
      sandwich assay the same preparation of polyclonal anti-FCS immunoglobulin (IgG)
      was used for coating the solid phase (as a capture antibody) and in a labelled
      form (I-125 labelled) for detection. The developed assay allows precise and
      accurate quantification of FCS proteins (down to 10 ng/ml) in vaccine
      preparations and has been used for screening of FCS residues (a) during
      production of measles vaccine, and (b) in various different commercial vaccine
      preparations. An enzyme-linked immunosorbent assay (ELISA) was also developed
      based on the same assay two-site sandwich principle, where anti-FCS was directly
      labelled with horse-radish peroxidase. ELISA was comparable in sensitivity and
      accuracy with IRMA.

PMID- 8297601
TI  - Quantitation of D antigen content in inactivated poliovirus vaccine derived from
      wild-type or sabin strains.
AB  - The enzyme-linked immunosorbent assay (ELISA) is currently the in vitro method
      for the measurement of the D antigen content of inactivated poliovirus vaccines
      (IPV) of greatest interest. The sensitivity and specificity of the test is
      dependent on the antibodies selected for use. We evaluated monoclonal and
      polyclonal antibodies for specificity to D antigen and wild or attenuated (Sabin)
      strains used in vaccine production. When used as detection antibodies the types 1
      and 2 monoclonal antibodies raised against wild-type poliovirus strains were D
      antigen-specific and cross-reactive with the corresponding Sabin strains. The
      type 3 monoclonal antibody was weakly cross-reactive with Sabin type 3 vaccine.
      In contrast, polyclonal antibodies were less D antigen-specific, but reacted
      equally well with wild-type and Sabin strain vaccines. The ELISA using monoclonal
      antibodies was shown to be highly reproducible. Reactivity with these monoclonal
      antibodies implies that a D-specific neutralizing epitope of each respective
      poliovirus type has been preserved in the inactivation process. Evaluation with
      additional neutralizing D antigen-specific monoclonal antibodies may be necessary
      to determine whether reactivity with one epitope of each type in an in vitro test
      is sufficient to predict potency of the vaccine in humans.

PMID- 8297602
TI  - Harmonization of requirements for influenza virus vaccines: the first year's
      experience with the EEC guideline.
AB  - An EEC guideline on the harmonization of requirements for influenza vaccines was
      published at the end of 1991. The document gives guidance on four different areas
      of harmonization. The 1992 production season was the first season during which
      this guideline was effective. The experience obtained as well as recommendations
      for further harmonization are discussed. After these important steps in the field
      of production and control of influenza vaccines, it is felt necessary to
      harmonize the use of influenza vaccines.

PMID- 8297603
TI  - Anomalous symptoms in mice injected with reverted tetanus toxoid.

PMID- 8297604
TI  - Interpharmacopoeial open conference. Harmonization of standards for biotechnology
      products. 20-22 April 1993, Verona, Italy.

PMID- 8297605
TI  - WHO/NIBSC workshop on genetic stability and product consistency of rDNA derived
      biologicals. November 23-24, 1992. Proceedings.

PMID- 8297606
TI  - Stability of genetic material in prokaryotes.

PMID- 8297607
TI  - Gene stability in mammalian cells and protein consistency.

PMID- 8297608
TI  - Organ dysfunction and cardiopulmonary bypass: the role of complement and
      complement regulatory proteins.
AB  - Cardiopulmonary bypass-induced organ dysfunction remains a clinical problem in
      certain groups of patients. Although the pathogenesis is multifactorial, it is
      likely that a panendothelial injury consequent upon widespread humoral and
      cellular activation is a major contributor to this process. The biologically
      active products of complement activation are certainly capable of inducing many
      of the features of the post-perfusion syndrome. The complex interactions between
      complement and many of the other proposed mediators of this response also
      supports this contention. However, it is equally certain that many of the other
      proposed mediators have some role to play. Inhibition of one cell type or
      inflammatory cascade is therefore unlikely to abolish all the adverse effects of
      CPB but will, at least in experimental systems, permit a more precise
      determination of the pathogenesis of this problem. The temptation to simply
      measure elevated circulating levels of newly identified mediators must be
      resisted and more effort applied to examining the pathophysiological effects of
      specific inhibitors. This type of investigation should initially be effected in
      experimental models where reproducible conditions can be ensured. In conjunction
      with this, far more precise end-points are required in order to assess the effect
      of any potential therapeutic intervention in a clinical setting. In particular,
      new techniques of evaluating endothelial injury need to be developed. In clinical
      studies careful consideration must be given to the patient population studied.
      Whilst patients undergoing routine coronary artery surgery form a relatively
      homogeneous group, the magnitude of endothelial injury sustained is probably
      small and, especially in terms of lung function, the signal will be diluted by
      other non-bypass-related events. The study of high risk groups would seem more
      appropriate despite their heterogeneity. An important unanswered question is why
      certain sub-populations of patients are at increased risk of clinically relevant
      bypass-induced injury. The endothelium of these patients may be different: the
      neonatal pulmonary microcirculation is not the same as that of an adult (with
      increased fluid filtration pressure and a higher microvascular surface area per
      unit lung mass [5,6]), children with pulmonary hypertension have histological
      evidence of an altered/damaged endothelium (S.G. Haworth, Personal Communication)
      whilst pre-existing sepsis could clearly induce a degree of endothelial
      dysfunction. A further possibility is that the inflammatory response in these
      patients is already "primed". Some patients with heart failure have been shown to
      have elevated circulating TNF.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8297609
TI  - Left ventricular geometry after endoventriculoplasty.
AB  - From 1988 to 1992, 65 patients underwent endoventriculoplasty (EVP) for
      anteroapical left ventricular aneurysm. The operative mortality was 4.6%, and
      9.2% needed intraaortic balloon counterpulsation (IABP). Forty-three patients
      were restudied by ventriculography and the preoperative and postoperative
      silhouettes were analyzed by means of a special computer program. In 24 patients
      computerized analysis showed a restored left ventricular (LV) geometry with
      symmetrical contraction pattern and a contractile apical segment. Residual
      deformity of the LV chamber associated with an asymmetrical contraction pattern
      was present in 19 cases. Data from these 43 patients were analyzed to detect
      predictive factors for successful heart geometry reconstruction. Univariate
      analysis revealed that the preoperative ejection fraction, global contraction
      score, and a non-aneurysmatic segments contraction score did not determine
      successful reconstruction. The presence of a preserved proximal septum (2.5 cm or
      more) on echocardiography was the only significant predictor. We would recommend
      liberal use of the EVP technique in patients with anteroapical LV aneurysm and
      preserved proximal septum in order to restore satisfactory LV geometry with a low
      operative risk. Caution must be taken when performing EVP in patients with
      fibrotic proximal septum.

PMID- 8297610
TI  - Control of ventricular rate by interatrial septal incision and crista terminalis
      myotomy in the patients with atrial fibrillation undergoing mitral valve
      replacement.
AB  - The aim of the study was to analyze the effect of surgical moderation of
      conduction from the atrium to the atrio-ventricular (AV) node on ventricular
      response in 30 patients with atrial fibrillation (AF) undergoing mitral valve
      replacement (MVR). Besides the usual diagnostics, echocardiographic evaluation of
      the size of the left atrium was performed in all patients, as a parameter of
      stability of rhythm conversion by drugs. Surgical treatment was applied
      exclusively in cases where, judging by these parameters, there was little chance
      for drug treatment to be effective. All patients (mean age 50 years) had severe
      mitral valve disease (NYHA III and IV), chronic AF and irregular ventricular
      rate, and underwent mitral valve replacement with mechanical valve. The patients
      were divided into three groups of ten patients each. In group I: MVR was combined
      with interatrial septal incision (IASI) to study the effect of the moderation of
      conduction from the interatrial septum to the AV node; in group II: after MVR,
      IASI was combined with crista terminalis myotomy (CTM) to study the additional
      effect of the moderation of conduction along the crista terminalis to the AV
      node; in group III (control): MVR was performed through left atriotomy, without
      antiarrhythmic incisions. Ventricular response was studied in two phases: In the
      immediate postoperative period (up to 7 days), using continuous
      electrocardiographic (ECG) monitoring, and 2 months postoperatively, using 24 h
      Holter monitoring with the results compared to a preoperative 24 h recording.
      Postoperative AF occurred in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297611
TI  - Emergency and elective cardiac retransplantation.
AB  - Among 265 patients transplanted at our Institution, 7 underwent cardiac
      retransplantation. There were five emergency retransplantations, the indication
      being graft failure in one case and acute rejection in four cases. Two patients,
      retransplanted because of acute rejection, had a positive panel reactivity
      antibody and a negative donor crossmatch. In the rejection cases
      immunosuppression was enhanced by perioperative plasmapheresis and a
      postoperative 1-month course of cyclophosphamide. In two cases emergency
      retransplantations were successfully performed despite a highly positive
      prospective crossmatch. Two patients underwent elective retransplantations for
      chronic rejection 12 and 41 months, respectively, after the primary transplants.
      The overall early and late survival rates are 71% and 57%, respectively, with a
      mean follow-up of 48.5 months. The early and late mortality for elective
      retransplantation is zero. Our experience confirms both the high operative risk
      for emergency retransplantation and the excellent results for elective
      retransplantation. The use of plasmapheresis and cyclophosphamide allowed us to
      undertake retransplantation successfully in 2 cases with positive donor
      crossmatch. Both hyperimmunized patients in our series were retransplanted
      because of irreversible acute rejection despite a negative crossmatch with the
      primary donor. The meaning of negative crossmatch in patients with preformed
      cytotoxic antibodies is therefore questionable.

PMID- 8297612
TI  - Spontaneous host endothelial growth on bioprosthetic valves and its relation to
      calcification.
AB  - We studied host endothelial growth and calcification of bovine pericardial valve
      prostheses treated with: (A) 0.625% glutaraldehyde + 4% formaldehyde, (B) 99.5%
      glycerol or (C) 99.5% glycerol + 4% formaldehyde. Twenty-three stentless
      chordally supported bileaflet pericardial mitral valves with treatments A (n =
      6), B (n = 6) or C (n = 11) were implanted in juvenile sheep for 125-273 days.
      After sacrifice, the anterior cusp from the annulus to papillary muscle of each
      valve was examined by scanning electron microscopy for the presence of
      endothelial cells, and the intrinsic calcification of each valve was determined
      by measuring calcium (micrograms/mg dry weight) from another 1 cm2 piece of
      grossly normal cusp. Sixty pieces of 1 cm2 pericardium with treatment A, B or C
      (n = 20 in each group) were implanted in 30 rats for 70 days. Calcium analysis
      and histology study of the implants were performed. In sheep, within a similar
      range of implantation periods, the endothelial growth rate of the valves was the
      highest in group B, 100% (6/6); group C was 45.5% (5/11) and A 16.7% (1/6). There
      were no significant differences in calcium among groups A, B and C. In rat
      implants, the calcium of group B was much lower than that of A or C (B = 6.92 +/-
      4.46 vs A = 144.52 +/- 27.66 or C = 240.54 +/- 13.47, P < 0.05) although its
      histology showed more severe degeneration and inflammatory changes. Pericardial
      mitral valves treated with glycerol show satisfactory biocompatibility with
      regard to host endothelial growth and prevention of calcification; however, these
      tissues show evidence of rapid degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297613
TI  - Continuous retrograde cerebral perfusion for protection of the brain during
      aortic arch surgery.
AB  - Hypothermic circulatory arrest and selective cerebral perfusion for aortic arch
      surgery have been reported, but these procedures are of limited duration, require
      hazardous and complicated techniques and can cause clamp injury. Continuous
      retrograde cerebral perfusion (CRCP) is a new and simple technique for the
      protection of the brain during hypothermic circulatory arrest. We applied CRCP in
      26 patients who underwent aortic arch surgery. Continuous retrograde cerebral
      perfusion was performed with a mean blood flow of 383 +/- 176, range 120-800,
      ml/min. The mean duration of CRCP was 63 +/- 15, range 32-92, min with the
      superior vena cava pressure at 15-42 mm Hg. No neurologic deficit was observed in
      20 patients (90%) and only minor deficits in 2 out of the 22 cases without severe
      postoperative complications, allowing evaluation of the effectiveness of CRCP.
      Four patients had other severe complications, and the effectiveness of the method
      could not be evaluated. Continuous retrograde cerebral perfusion can be an
      excellent and safe technique which avoids clamp injury during aortic arch
      surgery.

PMID- 8297614
TI  - Colon substitution for radical treatment of cardia and lower third esophageal
      cancer.
AB  - During the past 24 years we have treated 786 patients with esophageal and cardia
      carcinoma. En bloc resection of the tumor has been performed in only 461 (65.2%)
      of them and in 246 (34.7%) of the cases various palliative operations have been
      undertaken. Most of the patients were in stage II or III of the disease with
      squamous cell carcinoma in 80.5% and adenocarcinoma in 19.5% of them. The method
      of choice for the treatment of the patients with cardia and lower third of the
      esophagus carcinoma (n - 315) were blunt esophagectomy followed by colon (n -
      256), stomach (n - 54) and/or jejunal (n - 9) substitution. The histology results
      confirmed the oncologic radical zone of resection of the esophagus from 8 cm
      above the tumor to 10-12 cm below in the stomach wall. This is the reason why
      substitution of the esophagus with stomach tube is very often impossible and the
      colon substitution remains the method of choice for such patients. The other
      important factor is radical resection of the tumor with the surrounding tissue,
      organs and lymph nodes involved (resection en bloc). The hospital mortality
      included 28 patients (7.3%) from the radically operated who also underwent
      esophageal substitution (n = 378). For these patients the 3-year survival rate is
      51% (n - 191) and 5-year survival 46% (n - 172).

PMID- 8297615
TI  - Esophageal carcinoma with doubtful extirpability. Value of preoperative
      chemotherapy plus radiotherapy.
AB  - To improve resectability for bulky esophageal tumors and/or tumors evolving close
      to the pharyngo-esophageal junction (PEJ), a combined preoperative chemotherapy
      plus radiotherapy (CT+RT) was given in 25 patients. There were 23 men and 2 women
      (mean age: 55 years); 21 had squamous cell carcinoma and 4 had adenocarcinoma.
      According to TNM classification based on computed tomography, the tumor was
      graded T3 in 20 cases, T4 in 2, T2 in 2 and T1 in 1. The preoperative treatment
      included two sessions of continuous infusion of 5-fluorouracil (800 mg/m2 per
      day) and cisplatin (20 mg/m2 per day), and combined radiotherapy (3 Gy/day). The
      overall tolerance was acceptable. The tumoral mass decreased in 23 patients
      (92%). All the patients underwent a wide esophagectomy; among the six patients
      with a tumor close to the PEJ, two required an associated pharyngolaryngectomy.
      The operative mortality rate was 8%. Major non-fatal complications occurred in
      52%. On histology, there was no evidence of residual disease in seven patients
      (28%). The median survival was 18 months and the overall survival rate was 22.1%
      at 2 years. For the patients who had a complete histological response, the 2-year
      survival rate was 35%. Our data suggest that combined CT+RT may improve
      resectability of esophageal carcinoma. Improved survival rates seem to be
      appreciable in patients with a complete histologic response.

PMID- 8297616
TI  - Intraoperative contrast echocardiography for assessment of the surgical repair of
      coronary artery fistula.
AB  - We report two cases of acquired coronary fistula in whom fistula flow and
      surgical repair were evaluated intraoperatively by contrast echocardiography.
      Surgical repair was carried out through the left atrium because of the associated
      surgical procedure on the mitral valve. Contrast echocardiography allowed easy
      identification of the fistula openings in the left atrium and intraoperative
      control of the efficacy of the surgical closure. Contrast echocardiography is an
      ideal tool for the intraoperative diagnosis of effective interruption of a
      coronary fistula.

PMID- 8297617
TI  - Successful management of a tracheo-innominate artery fistula following placement
      of a wire self-expandable tracheal Gianturco stent.
AB  - The authors report a case of tracheo-innominate artery fistula secondary to
      tracheal perforation in an 18-year-old patient who is tetraplegic following
      cervical trauma. The patient had a very long tracheal stenosis, secondary to
      tracheostomy, which was managed by laser resection and a Gianturco stent. One of
      the anterior struts of the stent had eroded the trachea and the posterior wall of
      the innominate artery. Surgical management consisted of arterial resection, a
      longitudinal tracheal split incision to withdraw the stent and placement of a
      Montgomery T-tube. The patient has no respiratory discomfort 7 months after
      surgery.

PMID- 8297618
TI  - The use of Foley balloon catheters in cardiac surgery.
AB  - Situations may arise during elective and emergency surgery when vascular control
      is required but conventional vascular clamps cannot be used. We have found the
      Foley catheter useful for the control of inadvertent perforation of the heart
      especially in "redo" operations. We describe the use of the Foley catheter for
      the control of the difficult aorta and illustrate its potential versatility in a
      variety of uncommon situations. As Foley catheters are present in every operating
      theatre we hope that our experience will be of benefit to other surgeons who
      encounter similar problems.

PMID- 8297619
TI  - [The validity of the system of obligatory disease declaration for the
      epidemiologic surveillance of meningococcal meningitis].
AB  - In Spain meningococcic meningitis is a disease of obligatory declaration which is
      declared under the name of "Meningococcic infection". In this section other
      process are also included with the declaration being made under suspicion, with
      no knowledge of the degree of fulfillment and the significance of the official
      data. To know this the clinical history of meningitis patients of all the
      hospitals in Aragon from January 1985 to December 1988 were reviewed comparing
      the results with those from the system of obligatory disease declaration. The
      degree of fulfillment for meningococcic meningitis was 90% with the annual rates
      of incidence of meningococcic meningitis being 1.11 to 2.13 fold higher,
      according to hospitalary data, higher than the rates of the obligatory disease
      declaration system.

PMID- 8297620
TI  - [The apomorphine test in Parkinson's disease: diagnostic value].
AB  - The diagnosis of Parkinson's disease (PD) is difficult despite the use of strict
      clinical criteria. Apomorphine (APP) is a strong dopaminergic D1 and D2 agonist
      which has been used as a diagnostic test for PD by several authors. Sixty
      patients with a Parkinson's syndrome received subcutaneous doses of APP with
      diagnostic objectives. Ninety-four percent of the subjects with clinical criteria
      of PD responded positively to the bolus of subcutaneous APP. The remaining six
      percent had secondary effects limiting the usefulness of the test. Two point
      seven percent of the patients with atypical data of PD improved during
      performance of the test. Despite the limitations, this easily carried out test
      may be added to the recently proposed criteria of clinical diagnosis and may
      contribute greater certainty in diagnosis.

PMID- 8297621
TI  - [Myelopathy associated with HTLV-1: clinical electrophysiologic study].
AB  - Clinical and electrophysiological studies have been performed in 9 cases of HTLV
      I associated myelopathy (7 female, 2 male). Spastic paraparesis and neurogenic
      bladder were present in 8; sensory disturbances were detected only in 4. The
      conduction velocities of the posterior tibial and sural nerves were reduced in 2
      cases. Median nerve SSEP revealed a delay of N11, N13, N14, N20 peak latencies
      and an increase of N9-N20, N13-N14 and N13-N20 interpeak latencies. The
      electrophysiological studies are the most accurate indicators of the diffuse
      involvement not only of central motor and sensory pathways but also of the
      peripheral nervous system.

PMID- 8297622
TI  - [Additional tests in cerebral vascular diseases].

PMID- 8297623
TI  - [Unilateral hippocampal atrophy in refractory temporal lobe epilepsy].

PMID- 8297624
TI  - [Focal neuropsychological deterioration by posterior lobar atrophy (posterior
      cortical dementia)].
AB  - A right-handed 59 year old man who presented difficulties in the performance of
      complex acts (praxic) and spatial disorientation is described. Neurophysical
      exploration showed deterioration of the capacities linked to perceptive and
      spatial organization preserving the verbal capacities including the memory. After
      two years and a half of follow up practically no variation has been observed in
      his clinical manifestations with no implication of other superior mental
      function. CAT and MR findings revealed important posterior atrophy with an
      increase in the occipital loops. SPECT demonstrated cold images due to a
      bilateral parietal-temporal perfusion deficit. Discussion of the case leads to
      the needs of unifying the criteria and terminology for these focal degenerative
      processes.

PMID- 8297625
TI  - [Clinical iconographic dissociation in a case of monophasic demyelinating
      disease].
AB  - We report a patient with monophasic inflammatory demyelinizing disease whose
      initial symptoms and imaging studies led to the undertaking of a cerebral biopsy
      for suspicion of an expansive process. The evolution of the both the CT and MR
      imaging studies with contrast and overall the surprising size of the lesions in
      MR when the patient was clinically asymptomatic support the hypothesis of
      residual dysfunction in the hemato-encephalic barrier as a cause of the
      persistence of MR images. This explanation appears more acceptable than its
      attribution to a gliosis secondary to previous inflammation.

PMID- 8297626
TI  - [Thalamic abscess. A stereotaxically treatable lesion].
AB  - Solitary abscesses of the thalamus are an infrequent entity which carry serious
      problems with regard to treatment. We present a patient with an unknown septic
      focci who developed a right thalamic abscess due to Streptococcus constellatus
      and was treated by stereotaxic drainage for the suppuration and antibiotics. The
      patient was clinically and radiologically (CAT) controlled up until total cure of
      the lesion. Complications included dissemination of the infection to the
      meningeal space and a residual coreic picture controlled with tetrabenzine. The
      authors believe that evacuation by stereotaxic punction should be included among
      the therapeutic options available for deeply localized cerebral abscesses.

PMID- 8297627
TI  - [Isolated neuropathy of the trigeminal nerve as the first manifestation of
      primary Sjogren syndrome].

PMID- 8297628
TI  - [Transitory algic hemilateral syndrome in relation to spontaneous lobar
      hematoma].

PMID- 8297629
TI  - Protrusion, extrusion ... confusion!

PMID- 8297630
TI  - The clinical diagnosis of lumbar radiculopathy.
AB  - Lumbar radiculopathy may be caused by, or confused with, many different
      conditions. The nature of the patient's pain--its quality, intensity, location,
      and profile over time--is an important guide in the evaluation. A careful but
      directed physical examination is necessary for the clinical evaluation of
      patients with lumbar spine disease. Evaluation involves inspection of the back
      and limbs, palpation, and observation of the patient. A careful neurological
      evaluation, examination of strength, deep tendon reflexes, sensation, and
      muscular function is necessary. Electromyography is often useful. The most
      commonly involved nerve roots are L3, L4, L5, and S1. Lesions of each produce
      distinct symptoms, and other conditions can mimic the radiculopathies. Specific
      investigation is necessary for an accurate diagnosis.

PMID- 8297631
TI  - The acute lumbar disc herniation: imaging diagnosis.
AB  - The acute lumbar herniated nucleus pulposus (HNP) can often be diagnosed on good
      quality MRI or CT examination. Myelography, discography, and
      postmyelography/postdiscography CT ordinarily are reserved for equivocal and
      protracted cases. MRI is recommended as the initial study of choice except for
      older patients for whom CT may be more valuable because of the high incidence of
      osteophytosis. Patients with acute herniated nucleus pulposus (HNP) may have
      varied clinical symptoms depending on the level of the HNP, extent of the annulus
      tear/depth of penetration of nuclear material, and the direction of the disc
      herniation. HNP does not necessarily produce radiculopathy and may cause vague
      low back pain. This article reviews and analyzes the clinical symptoms and
      problems associated with HNP, as well as the pitfalls and differential diagnostic
      possibilities in interpretation.

PMID- 8297632
TI  - Pathophysiological basis of lumbar disc degeneration: imaging analysis.
AB  - This article provides a brief synopsis of the pathoanatomic basis of disc
      degeneration. An attempt is made to correlate CT, MR and CT discographic
      findings. The T2-weighted sagittal images are the most sensitive for evaluating
      disc degeneration. The contour changes on axial CT and MR scans are sensitive for
      abnormalities but not always specific. The CT discogram adds information
      unavailable by other imaging methods pertaining to the internal architecture of
      the disc. It additionally defines focal nuclear herniations and also is helpful
      in evaluating the stage of disc degeneration.

PMID- 8297633
TI  - Imaging anatomy of the lateral lumbar spinal canal.
AB  - This article reviews the normal anatomy of the bony and soft tissue structures of
      the lateral lumbar spinal canal. Thorough knowledge of these imaging anatomy
      helps in making the correct diagnosis of the lumbar spinal lesions. CT and MRI
      are excellent tools to diagnose lateral lumbar spinal canal stenosis. Both CT and
      MRI provide the accurate measurements of the midsagittal and lateral spinal
      canals and show the abnormalities of the nerve root course. This review provides
      anatomic and radiographic descriptions of the lateral lumbar spinal canal and the
      anatomically related joints.

PMID- 8297634
TI  - Nondiscogenic lumbar radiculopathy: imaging considerations.
AB  - This article reviews the differential diagnosis of lumbar radiculopathy, clinical
      presentations of spinal stenosis, pathological anatomy, and roentgenographic
      considerations of lumbar spinal stenosis. Most patients suspected of symptomatic
      spinal stenosis should have plain roentgenograms first to rule out other obvious
      lesions and to evaluate disc space and foraminal narrowing. Plain roentgenograms
      also show the sagittal and coronal deformities if present. The next procedure for
      the evaluation of spinal stenosis after plain roentgenograms should be MRI, as
      myelogram or CT can be avoided in most cases. In select cases, patients who
      cannot get MRI or those who underwent MRI with unresolved questions should have a
      myelogram or CT for further evaluation.

PMID- 8297635
TI  - The postoperative lumbar spine: imaging considerations.
AB  - MRI with intravenous contrast has recently become the imaging modality of choice
      in the evaluation of patients developing recurrent back pain or symptoms
      following laminectomy and/or discectomy. The normal postoperative appearance is
      important to recognize because a number of changes occur normally throughout the
      healing period. The difference between epidural scar and recurrent disc
      herniation can usually be determined on MRI. Postoperative fluid collections may
      also develop. Disc space infection, although uncommon, is a critical diagnosis,
      but can be confused with degenerative end plate changes. Arachnoiditis and spinal
      stenosis also show characteristic imaging findings.

PMID- 8297636
TI  - Imaging basis of disc space infection.
AB  - Infective spondylitis, the combined infection of the osseous vertebral structures
      and disc space, constitutes 2% to 4% of all cases of osteomyelitis, and is
      increasing in prevalence. Differences in clinical and imaging presentation
      between children and adults are explained by developmental anatomic differences.
      Radiographic evaluation of infective spondylitis has previously included plain
      films, CT scans and nuclear imaging. However, MRI is emerging as the most
      sensitive and specific modality for early detection of pyogenic and nonpyogenic
      infections and their complications, as well as in follow-up evaluation.
      Degenerative disc disease, seronegative spondyloarthropathies, and
      spondyloarthropathy associated with long-term hemodialysis may mimic the imaging
      abnormalities of infective spondylitis.

PMID- 8297637
TI  - MRI of benign lumbosacral nerve root enhancement.
AB  - Enhancement of nerve roots in the lumbosacral spine after intravenous
      administration of gadolinium contrast agents is seen in benign conditions such as
      disc herniation and spinal stenosis and may be observed in either the unoperated
      or postoperative spine. Correlating reasonably well with the clinical syndrome,
      nerve root enhancement represents actual pathology within nerve roots reflected
      by this breakdown in the blood-nerve barrier. Nerve root enhancement may be used
      in certain circumstances to show and confirm clinically relevant neurological
      disease.

PMID- 8297638
TI  - Percutaneous discectomy: an update.

PMID- 8297639
TI  - Prediction of cancer incidence in the Nordic countries up to the years 2000 and
      2010. A collaborative study of the five Nordic Cancer Registries.

PMID- 8297640
TI  - Fetal antigen 2 (FA2): the aminopropeptide of the alpha 1 chain of human type I
      procollagen. A study on skin, tumour biology and bone metabolism.
AB  - Fetal antigen 2 (FA2) was purified from second trimester human amniotic fluid
      (AF) using immunospecific chromatography, gel filtration and reversed phase
      chromatography. Amino acid composition and sequence analyses of purified FA2
      revealed identity to the amino acid sequence of the aminopropeptide of the alpha
      1 chain of human type I procollagen. Gel filtration of AF as well as purified FA2
      demonstrated two molecular forms of FA2, which during gel filtration were
      elucidated corresponding to MW of approximately 100 kDa and 30 kDa. The molecular
      forms were referred to as the high molecular component (FA2-HM) and low molecular
      component (FA2-LM), respectively. SDS-PAGE analysis (reducing and nonreducing
      conditions) showed a MW of 27 kDa for both FA2-HM and FA2-LM. Mass spectrometry
      analysis however revealed a MW of 14.343 +/- 3Da. Proteins with collagenous
      domains often reveal aberrant behaviour both in gel filtration and SDS-PAGE and
      this phenomenon may account for the apparent higher MW of FA2 observed using
      these techniques compared to mass spectrometry and amino acid
      composition/sequence analyses. A polyclonal, monospecific rabbit antibody raised
      against FA2 was used in immunohistochemical localization studies. Due to the
      obvious association of FA2 to the BM structure in adult and fetal skin, it was
      initially referred to as a BM associated component. However, FA2 was
      immunologically distinct from the well established BM components and moreover,
      the diffuse distribution of FA2 along the BM differed from linear localization of
      BM components (e.g. collagen type IV and laminin). The identification of FA2 as
      the aminopropeptide of the alpha 1 chain of human procollagen type I has the
      implication that in the immunohistochemical investigations the anti-FA2 may not
      distinguish between the free propeptide and procollagen type I. In the papillary
      dermal region of human adult skin type I collagen are arranged in loose fibrils
      to which the aminoterminal propeptide is still attached. Anti-FA2 may recognize
      epitopes in the type I procollagen present in this region, giving rise to the
      diffuse FA2 distribution along the BM. However, whether FA2 also appear as a free
      component in this region is unknown. In fetal skin where collagen is vividly
      layed down in the mesenchymal compartment staining with anti-FA2 revealed a
      diffuse mesenchymal distribution. Demonstration of FA2 within the cytoplasm of
      proliferating fibroblasts and diffusely in granulation tissue during wound
      healing suggest that FA2 was involved in the reparative processes.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8297641
TI  - Treatment of brain tumours in children less than 3 years of age.

PMID- 8297642
TI  - The chemotherapy of colon cancer can no longer be ignored.

PMID- 8297643
TI  - Surgical resection plus tamoxifen as treatment of breast cancer in elderly
      patients: a retrospective study.
AB  - Between March 1982 and May 1989, 151 women with primary breast cancer ranging in
      age from 70 to 91 years (median 79), were treated with conservative surgical
      procedure followed by adjuvant tamoxifen. Surgery was performed under local
      anaesthesia without axillary node dissection. The median duration of follow-up
      was 60 months (range 36-124). There were six local, six ipsilateral axillary node
      and six distant relapses. Local recurrences were successfully managed with
      further surgery whereas axillary node relapses required radiotherapy in 3 cases,
      surgery in 2 cases and hormonal treatment in 1 case. 2 patients died of
      progression of disease and one of unrelated conditions. The 5-year relapse-free
      survival rate was 0.82. This treatment option in elderly patients yields an
      acceptable local control and reduces the risks of major surgery.

PMID- 8297644
TI  - The cosmetic outcome in early breast cancer treated with sector resection with or
      without radiotherapy. Uppsala-Orebro Breast Cancer Study Group.
AB  - In a randomised trial, the cosmetic results after sector resection and axillary
      dissection with or without postoperative radiotherapy for early breast cancer
      were evaluated. The evaluations were made at 3, 12, 24 and 36 months (357, 326,
      302 and 255 women, respectively) after treatment. Good to excellent cosmetic
      results were achieved in 84-90% of those in the group randomised to radiation and
      in 91-95% in the group allocated to surgery only, as judged by the women
      themselves, and in 81-86% and 87-93%, respectively, according to other observers.
      At 12 months the results in 290 patients were photographically documented and
      evaluated by a panel. The results were good to excellent in 35-84% of the
      irradiated group and in 62-93% of the non-irradiated group. Poor results followed
      the development of contour differences, breast oedema and mamillary deviation,
      which were the most important mediators of a poor cosmetic result after
      radiotherapy. We conclude that sector resection and axillary dissection can be
      performed with good cosmetic results. Doses to 54 Gy of radiotherapy influence
      the result negatively, but from a clinical standpoint to a moderate extent.

PMID- 8297645
TI  - Grading of soft tissue sarcomas: experience of the EORTC Soft Tissue and Bone
      Sarcoma Group.
AB  - A practical grading system for soft tissue sarcomas was developed, based on 282
      eligible patients entered in an EORTC adjuvant clinical trial. The primary
      tumours in this trial had to be adequately treated. Histopathological parameters,
      which appeared significant in two preceding studies, were tested. These
      parameters were differentiation of the tumour, presence and amount of necrosis,
      the presence and amount of myxoid areas and the number of mitoses. In addition,
      the size of the tumour was also analysed. The quantitative data (mitotic count
      and size of the tumour) were not a priori grouped, but were divided into
      categories based on the results of the statistical analysis. Based on a
      multivariate analysis only mitotic count, the presence or absence of necrosis and
      the size of the tumour were significantly correlated with the duration of
      survival or the time to distant metastases. Of these parameters, the mitotic
      count was the most important.

PMID- 8297646
TI  - Radioimmunoscintigraphy using [111In]antimyosin Fab fragments for the diagnosis
      and follow-up of rhabdomyosarcoma.
AB  - Between 1987 and 1992, 39 radioimmunoscintigraphic studies using 111In-labelled
      antimyosin Fab fragments were performed in 27 patients with rhabdomyosarcoma
      (RMS), 2 patients with leiomyosarcoma (LMS) and 1 with alveolar soft tissue
      sarcoma. 21 patients were children aged 3-14 years. These patients, who had
      histologically proven myosarcoma, were examined scintigraphically to search for
      local recurrences or metastases and to determine the response to treatment. The
      results of immunoscintigraphy were compared with histopathological parameters and
      other imaging modalities. The sensitivity of antimyosin scintigraphy in this
      series was 82% and the specificity was 73%. Although the technique appears to be
      not highly specific for RMS, it was found to be useful for the early detection of
      local recurrence and metastases, as well as for the evaluation of the response to
      therapy.

PMID- 8297647
TI  - Cancer morbidity in blood recipients--results of a cohort study.
AB  - Blood transfusions involve the transfer of relatively large volumes of body
      fluids and cellular material between individuals. A variety of pathogens like
      viruses, some of which are associated with development of certain tumours, are
      known to be transmitted by this route. Blood recipients were identified during
      1981-1982 in the register of the hospital blood centre, and in-patients by the in
      patient and discharge register of the hospital. Tumour occurrence and vital
      status were determined by means of the population-based regional tumour register.
      Age, gender and calendar-year specific rates from the general population were
      used to calculate expected values. In a cohort study of 3177 blood recipients,
      increased numbers of malignant lymphomas [13 vs. 4.8 expected, standard morbidity
      ratio (SMR) 2.70 95% confidence interval (CI) 1.44-4.62] and skin cancers [12 vs.
      5.2 expected, SMR 2.29, 95% CI 1.19-4.01] were seen 3 to 9 years after
      transfusion. In a second cohort study of 29,910 hospitalised patients, a total of
      37 (29.8 expected) malignant lymphomas was found in 28,338 patients with no
      transfusion and 10 (2.73 expected) in 1572 patients with a transfusion, 3 to 9
      years after the hospitalisation. The incidence rate ratio between these groups
      was 3.11 (95% CI 1.56-6.20) using a Mantel-Haenszel estimator with age
      stratification. Non-melanomatous skin cancers had an incidence ratio of 2.74 (95%
      CI 1.25-6.00). We conclude that, in the cohorts discussed here, malignant
      lymphomas and skin cancer occur more often in blood recipients than in controls.
      It remains to be established whether this is due to factors covariating with
      transfusion or by the transfusion itself. Further studies on these putative
      associations are warranted, as are analytical studies of the epidemiology of
      malignant lymphomas, especially non-Hodgkin's lymphoma, whose aetiology is still
      poorly understood.

PMID- 8297648
TI  - Mitoxantrone, leucovorin and high-dose infusional 5-fluorouracil: an effective
      and well-tolerated regimen for the treatment of advanced breast cancer.
AB  - Mitoxantrone and 5-fluorouracil (5-FU) are active drugs with a favourable
      toxicity profile in advanced breast cancer. The activity of 5-FU can be enhanced
      by modulation with leucovorin. Continuous infusion of 5-FU yields a superior
      activity with less toxicity compared with bolus injections. 27 patients with
      advanced breast cancer, 22 of them pretreated, received intravenous (iv)
      mitoxantrone, 14 mg/m2, day 1, iv leucovorin, 300 mg, days 1 and 15, and 5-FU, 4
      g, 48-h infusion, days 1 and 2, 15 and 16, once every 28 days (MLF regimen).
      Leucovorin was administered either as a bolus prior to the 5-FU infusion or mixed
      together with the 5-FU during the first 24 h. There were 12 partial responses, 9
      patients had stable disease, and 5 had progressive disease. 1 patient was not
      evaluable because of concomitant irradiation of the target lesion. The overall
      response rate was 46%; for previously untreated patients it was 100% and for
      pretreated patients it was 33%. Grade 3 nausea/vomiting was noted in 7 evaluable
      patients (26%) and grade 4 haematological toxicity in 1 patient (4%). Only 1
      patient had complete alopecia. The median duration of response was 13 months in
      untreated, and 12 months in pretreated patients. It was concluded that MLF is an
      active regimen in advanced breast cancer, even in highly pretreated patients,
      with moderate and manageable toxicity. Assessment in first-line treatment appears
      to be of interest.

PMID- 8297649
TI  - Phase I/II study of low-dose intravenous OKT3 and subcutaneous interleukin-2 in
      metastatic cancer.
AB  - In a phase I/II study the safety, immunostimulatory and antitumor effects of a
      combined OKT3/interleukin 2 (IL-2) treatment was studied in 15 cancer patients
      who failed IL-2 treatment. OKT3 was given as a 2-h intravenous infusion. Doses of
      50, 100, 200 and 400 micrograms OKT3 were studied. Within 24 h, subcutaneous IL-2
      was started 5 days/week for 4 weeks, at a dose of 9-18 x 10(6) U daily. Maximum
      tolerated dose was 400 micrograms OKT3 with neurotoxicity as dose-limiting
      toxicity. Toxicity of subcutaneous IL-2 was acceptable. At the maximum tolerated
      dose, 9 patients with renal cell carcinoma with measurable disease were treated
      in a phase II setting. 8 patients were evaluable for response. 4 patients had
      stable disease and 4 had progressive disease. An increase of activated lymphocyte
      subpopulations could not be found, although OKT3 was detectable on lymphocytes in
      vivo. Only if laboratory studies shed light on methods of improving
      immunostimulating effects of OKT3 will further clinical studies be warranted.

PMID- 8297650
TI  - Prognostic significance of the CaMBr1 antigen on breast carcinoma: relevance of
      the type of recognised glycoconjugate.
AB  - An extensive study of the expression of the blood group-related antigen CaMBr1
      has been performed by immunohistochemistry, immunoblotting and high performance
      thin layer chromatography both on frozen and paraffin-embedded (paraffin) samples
      from normal and neoplastic breast tissues. The glycolipid antigenic fraction
      (from frozen samples) was preferentially expressed on functioning breast
      epithelium. In a prospective series of 143 breast cancer cases CaMBr1 expression
      was associate, on frozen sections, with the transferrin receptor (P = 0.01), the
      positivity with oestrogen receptor immunochemical assay (P = 0.06), premenopausal
      status (P = 0.06) and node negativity (P = 0.07). Non-significant correlation
      with longer disease-free survival (DFS) was observed. In a retrospective series
      of 862 cases on paraffin sections the glycoproteic antigenic fraction was
      significantly associated with premenopausal status (P < 0.05) and lobular
      histotype (P < 0.01), but failed to predict survival, although a trend for longer
      DFS was observed for positive cases.

PMID- 8297651
TI  - Cytokine gene expression in primary brain tumours, metastases and meningiomas
      suggests specific transcription patterns.
AB  - To obtain an insight into the network of cytokine gene transcription in the brain
      tumour microenvironment, we investigated the expression of genes encoding for
      interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, interferon
      (IFN)-gamma, granulocyte-macrophage colony-stimulating factor, tumour necrosis
      factor (TNF)-alpha and transforming growth factor (TGF)-beta 1, -beta 2 and -beta
      3 in freshly excised brain tumour samples and autologous peripheral blood
      mononuclear cells. Tissue specimens from 15 primary brain tumours, three brain
      metastases, five meningiomas, autologous peripheral blood mononuclear cells
      (PBMC) and three brain tumour cell lines were tested by reverse polymerase chain
      reaction. Despite the presence of T-lymphocytes, cytokine gene transcripts
      typically detectable upon T cell receptor triggering could not be observed in
      central nervous system tumours of diverse histology. In primary brain neoplasms,
      transcription of genes encoding for the inhibitory cytokines TGF-beta and IL-10
      was detectable in more than 50% of samples. IL-6 transcripts could only be
      detected in malignant gliomas. In brain metastases, virtually no cytokine gene
      transcripts could be observed. Surprisingly, TGF-beta transcripts were also
      detected in all meningiomas. Thus, transcription of genes encoding for inhibitory
      factors appears to prevail in primary brain neoplasms.

PMID- 8297652
TI  - Deoxycytidine kinase and deoxycytidine deaminase activities in human tumour
      xenografts.
AB  - Deoxycytidine kinase (dCK) and deaminase (dCDA) are both key enzymes in the
      activation and inactivation, respectively, of several deoxycytidine
      antimetabolites. We determined the total dCK and dCDA activities using standard
      assays, in 28 human solid tumours grown as xenografts in nude mice, and four
      corresponding cell lines. dCK activities in colon tumours varied from 11 to 12
      nmol/h/mg protein, in ovarian tumours from 3 to 10 nmol/h/mg protein, in soft
      tissue sarcomas from 2 to 7 nmol/h/mg protein and in squamous cell carcinomas of
      the head and neck about 45-fold, between 0.4 and 18 nmol/h/mg protein. The dCDA
      activities showed a larger variation, from 243 to 483, 14 to 1231, 3 to 7 and 1
      to 222 nmol/h/mg protein, respectively. The ratios of dCK vs. dCDA activities in
      these tumours varied from 0.025 to 0.046, 0.004 to 0.240, 0.581 to 1.123 and from
      0.012 to 4.227, respectively. In four cell lines (A2780, OVCAR-3, WiDr and UM-SCC
      14C), sources for some of the above mentioned tumours, a different pattern in dCK
      and dCDA was observed than in the corresponding tumours. The variation in dCDA
      activities was in a smaller range (20-fold) than in the tumours (40-fold). In all
      cell lines dCK activity was higher than dCDA activity, in contrast to the
      corresponding tumours, in which the reverse pattern was observed. Previously,
      some of the tumours were tested for sensitivity to the deoxycytidine analogues 5
      aza-deoxycytidine and 2',2'-difluorodeoxycytidine. In the sensitive tumours, both
      the highest and lowest dCK activity was observed, indicating that dCK activity in
      solid tumours is high enough to activate deoxycytidine analogues.

PMID- 8297653
TI  - Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in
      vitro and in vivo.
AB  - The effects of long-term tamoxifen exposure on cell growth and cell cycle
      kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER
      negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen
      exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle,
      and slowed the doubling time of cells from 30 to 59 h. These effects corresponded
      to an increase in the cellular accumulation of tamoxifen over time [mean area
      under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in
      the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on
      the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50
      mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of
      MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56
      days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and
      MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted
      in the rapid growth of tetraploid tumours. The tetraploid tumours maintained
      their ploidy following tamoxifen treatment for nine consecutive serial
      transplantations. Histological examination of the fifth transplant generation
      xenografts revealed that the tetraploid tumour had a 25-30 times greater mass,
      area of haemorrhage and necrosis, a slightly higher mitotic index and was more
      anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours
      maintained a stable ploidy following tamoxifen treatment until the eighth and
      ninth transplantation, when a tetraploid population appeared, suggesting that
      tamoxifen treatment may select for this clone in vivo. These studies suggest that
      prolonged tamoxifen exposure may select for new, stable, fast growing cell clones
      in vitro as well as in vivo.

PMID- 8297654
TI  - Side-effects of screening.
AB  - There has been a 42% increase in the number of mammograms performed outside the
      national screening programme (operating in Camberwell, southeast London) which
      was not anticipated in the Forrest Report, a document to the Health Ministers of
      the U.K. by a working group chaired by Sir Patrick Forrest. The report compiles
      recommendations on breast screening, using mammography and breast self
      examination, to reduce the mortality in women aged 50-64 years. This 42% increase
      is attributable mainly to referrals from menopause clinics and general
      practitioners of patients mainly in the screening age group. When we looked at
      referrals from general practitioners, suspicious mammographic findings were
      reported in 20% of patients referred with a breast lump, in contrast to only 4%
      of patients referred with breast pain or nodularity. Better education of both the
      public and general practitioners, concerning the signs and symptoms of breast
      cancer, may reduce demands to perform mammographies outside the current national
      screening programme.

PMID- 8297655
TI  - Biological, physical, mental and social dimensions of breast cancer: information
      based on routine case notes.
AB  - 551 patients were diagnosed with breast cancer in Tampere University Hospital
      district, Finland between 1977 and 1980. The number of follow-up visits during
      the first 5 years was 8248. The biological, physical, mental and social
      dimensions of breast cancer were measured by death, recurrence of disease,
      Karnofsky score, physical or mental symptoms, and sick leave. The prevalence
      rates of an event and the incidence rates of the appearance or disappearance of
      an event were used to determine the indicators for these different dimensions of
      breast cancer. The study was based on hospital case notes. Data on death,
      recurrence, sick leave and Karnofsky score were well recorded, but physical or
      mental symptoms were recorded infrequently. There was a 4-fold difference between
      the highest and lowest prevalence for the different dimensions, but the trends
      were similar by follow-up time. The variation was also large for the incidence
      rates but the trends differed with length of follow-up time. The biological,
      physical, mental and social consequences of breast cancer differ in magnitude and
      have different trends over time, indicating that breast cancer is a different
      disease depending on the dimension and on the indicator under consideration.

PMID- 8297656
TI  - Patterns of metastatic breast cancer in relation to histological type.
AB  - We have examined the clinical records fo 1238 patients with operable breast
      cancer to identify the sites of metastatic disease. Infiltrating ductal carcinoma
      (IDC) recurred more commonly in lung (P < 0.05), pleura (P < 0.05) and brain (P <
      0.05), while infiltrating lobular carcinoma (ILC) more commonly metastasised to
      the bone marrow (P < 0.01) and peritoneum (P < 0.01). Bone involvement as the
      initial presentation of distant metastatic disease occurred in over 50% of women
      with ILC, significantly more commonly than in those with IDC (34%, P < 0.01).
      Survival was similar for the two groups, both from time of diagnosis and from
      time of development of distant metastases.

PMID- 8297657
TI  - Expression of major histocompatibility complex (MHC) antigens and their loss on
      culture in renal carcinoma.
AB  - Biopsies from the tumour and the adjacent normal kidney were obtained from 15
      patients with renal cell carcinoma (RCC). The proximal convoluted tubules from
      which the tumour arose expressed major histocompatibility complex (MHC) class I
      antigen (Ag) in 3 cases and class II in none. By contrast, the carcinoma cells
      expressed class I Ag in 14 cases and class II Ag in 5 cases. Cells from each
      carcinoma were established in culture. As the culture period increased, cells
      from six of eight RCC showed diminished expression of class I Ag and five of six
      reduced expression of class II Ag. This is similar to the relative loss of class
      I Ag in synchronous metastases from RCC.

PMID- 8297658
TI  - Mammographic patterns in breast cancer chemoprevention with fenretinide (4-HPR).
AB  - In 1987 a chemoprevention trial was started at the Istituto Nazionale Tumori of
      Milan to evaluate the efficacy of fenretinide or 4-HPR (an effective agent
      against carcinogen-induced epithelial tumours in experimental animals) in
      reducing the incidence of contralateral breast cancer in women previously treated
      for an early breast cancer (pT1, pT2, N-). Patients were randomised into two
      groups: 4-HPR 200 mg/day vs. no treatment. We reviewed the mammograms of 149
      patients who received 4-HPR for at least 4 years to examine whether changes seen
      in the mammary glands of rats could also be seen in women. For each patient, at
      least five mammograms (one at baseline and four annual controls) of the
      contralateral breast were classified according to Wolfe's parenchymal patterns
      (N1, P1, P2, DY). With the daily dosage of 200 mg and after follow-up, no changes
      in mammographic patterns were observed.

PMID- 8297659
TI  - Familial and genetic aspects of colorectal carcinogenesis.
AB  - There is abundant clinical and pathological evidence which suggests that
      colorectal cancer arises in a sequential manner through a series of events that
      can be followed during the progression of the disease from early adenoma through
      to metastatic disease. The molecular events that are associated with the
      initiation and progression of the disease are gradually being unravelled. As the
      molecular characterisation of colorectal cancer continues, new mechanisms by
      which the disease progresses are becoming evident. In this short review, a brief
      description of current knowledge of colorectal cancer development is presented.

PMID- 8297660
TI  - Trends in cancer mortality, 1955-1989: Asia, Africa and Oceania.

PMID- 8297661
TI  - [Erythromelalgia--review of clinical characteristics and therapy].

PMID- 8297662
TI  - [Identification of the central sulcus using magnetoencephalography and
      neuronavigator].
AB  - The brain-generated currents that produce potentials measured by the
      electroencephalogram also produce magnetic fields which can be measured by the
      magnetoencephalogram (MEG), N 20 compatible evoked field after median nerve
      stimulation is known to be generated in primary sensory cortex. Using MEG with 37
      channel SQUIDs, a current dipole is back traced which corresponds to the sensory
      cortex. When the dipole is projected onto the MRI of the same patient, the
      primary sensory cortex is precisely identified in the MRI images. These data were
      used as the key images for navigator enabling a surgeon identify the central
      cortex in the surgical field. Seven patients with peri-central mass lesion (3
      meningiomas, 1 metastatic tumors, 1 angiomas, 2 gliomas) underwent surgery under
      MEG-navigator method. In every case, the central sulcus and motor cortex were
      easily identified on the cortex and the tumor was removed as far as possible
      preserving the motor strip. There were no postoperative worsening of the motor
      paresis and no other complications were noticed. The method which combines the
      MEG functional mapping and navigator was considered to be a powerful tool in
      surgery of the pericentral mass lesions.

PMID- 8297663
TI  - [Effect of enalaprilat, an angiotensin converting enzyme inhibitor, on the
      membrane potential of cultured neuroblastoma-glioma hybrid NG108-15 cells].
AB  - The effect of enalaprilat on the membrane potential of cultured neuroblastoma
      glioma hybrid NG108-15 cells was investigated using the current clamp method. The
      NG108-15 cell line characteristically differentiates into neurons after addition
      of 1 mM dibutyryl cAMP to the culture medium. First it was found that enalaprilat
      inhibits both sodium and calcium currents in the cell membrane of differentiated
      NG108-15 cells. At concentrations between 10 and 100 microM, this inhibitory
      effect was reversible and transient, and occurred in a dose-dependent manner.
      Prolonged washing with normal saline (> 20 min) was needed to completely reverse
      the inhibitory effect of enalaprilat. The higher the concentration of
      enalaprilat, the greater its suppressant action on the membrane potential, and at
      high concentrations (100 microM), enalaprilat caused the peak membrane potential
      to disappear. When cells were incubated with enalaprilat, 100 microM, for longer
      periods, however, this inhibitory effect appeared to become irreversible. These
      findings suggest that enalaprilat has an inhibitory effect on the
      electrophysiological activity of neurons especially on membrane calcium currents.

PMID- 8297664
TI  - [Neuropathological study of autosomal dominant ataxia linked to loci on
      chromosome 6p (SCA 1)].
AB  - We reported an autopsy case of hereditary OPCA genetically proved to be SCA 1.
      Clinically, he showed cerebellar ataxia from beginning to the end stage, and was
      characterized by slow eye movement with external ophthalmoplegia, pyramidal tract
      signs, generalized amyotrophy including facial muscle, mild bulbar paresis, mild
      dementia, and urinary disturbance. Neuropathologically, the degeneration and loss
      of neurons with gliosis were seen in the Purkinje layer, dentate nucleus of the
      cerebellum, inferior Olive nucleus, motor nucleus of cranial nerve, anterior horn
      of the spinal cord, and column of the Clarke. And the myelinpallor was revealed
      in the connecting nerve fiber of these lesions, posterior column and
      spinocerebellar tract of the spinal cord.

PMID- 8297666
TI  - [A case of transient vertical gaze palsy following right thalamic and midbrain
      infarction].
AB  - The authors report a 71-year-old male who suffered from vertical gaze palsy due
      to infarction localized on MRI in the right midbrain. Vertical gaze palsy was
      observed 1 hour after the onset of his stroke. Upgaze palsy was noted the
      following day. Four days later, the disturbances of ocular movement disappeared.
      T2 weighted MR imaging showed a high signal intensity lesion, which was localized
      in the right side of the thalamo-mesencephalic portion. However, since the
      vertical gaze palsy appeared only transiently for a short time in the initial
      stage and since the level of consciousness decreased during that time, it was
      suggested that there was a bilateral functional disorder caused by mild edema,
      etc., in the hyperacute stage, which was not demonstrated on MRI. This disorder
      had been overlooked either because the duration of the vertical gaze palsy due to
      the unilateral lesion was very short, i.e. improvement was seen 4 days after
      onset, or the lesion was not clearly delineated in a CT scan of the head. It
      appeared possible that this sign might not be very rare if careful observations
      are performed in the hyperacute stage of midbrain infarction.

PMID- 8297665
TI  - [Two cases of acute alcoholic myopathy associated with rhabdomyolysis].
AB  - We reported two cases of acute alcoholic myopathy associated with rhabdomyolysis.
      The first case was 62 year-old man, who had been drinking every day for 40 years.
      Following diarrhea, he had psychic symptoms, and was admitted to our hospital. He
      was in a state of delirium. Tremor in extremities, dysarthria and weakness of
      lower extremities were observed. Neither swelling nor grasping pain were seen in
      any muscles. Laboratory data showed severe hypokalemia and high levels of serum
      muscle enzymes and myoglobin. An increase of lactate and pyruvate was not seen in
      ischemic exercise test performed at the acute or the recovery phase. It was
      suggested that glycolysis in muscles was suppressed in this case. The second case
      was 43 year-old man, who had been drinking every day for 27 years. Rapidly
      progressive weakness of both lower extremities was seen, and he was admitted to
      our hospital. Grasping pain of both legs and proximal muscle weakness of
      extremities were observed. Laboratory date showed normokalemia and high levels of
      serum muscle enzymes and myoglobin. Muscle biopsy showed no abnormal findings in
      histology and electron microscopy. Although the pathogenesis of acute alcoholic
      myopathy is unknown, suppression of muscle glycolysis enzyme caused by ethanol
      may play an important role in the first case.

PMID- 8297667
TI  - [Hypoglycemic encephalopathy demonstrating generalized multiple cortical
      infarctions--sequential CT findings].
AB  - A fifty-nine-year-old alcoholic man with severe hypoglycemic encephalopathy was
      examined using sequential CT scans of the brain (CT). Twenty-seven hours after
      the attack, which resulted in a comatose state, CT disclosed multiple low density
      areas throughout the cerebral cortex which resembled multiple cortical
      infarctions. CT obtained four days after the ictus demonstrated more prominent
      low density areas in the cerebral cortex, diffuse cerebral edema and partial
      cortical enhancement after administration of contrast medium. Sixteen days after
      the ictus, the multiple low density areas in the cerebral cortex disappeared.
      Enhanced CT on day 23 demonstrated marked gyral enhancement throughout the
      cerebral cortex. Thereafter diffuse brain atrophy progressed rapidly as
      demonstrated by MRI on day 82 which showed extensive cortical and subcortical
      atrophy particularly in the frontoparietal and parieto-occipital regions
      bilaterally with dilated lateral ventricles. Hypoglycemia and anoxia have long
      been thought to give rise to similar types of brain damage based on
      neuropathological observations. But it has recently been shown that they are
      quite different based on neurochemical and neurophysiological findings. Numerous
      previously reported autopsy cases of hypoglycemia confirm these findings which
      are neuropathologically similar to the multiple infarction seen in the present
      case. We conclude that the acute cortical changes of the present case are
      specific for hypoglycemic encephalopathy. The findings indicate that the basic
      mechanisms operating in hypoglycemia and anoxia are different.

PMID- 8297668
TI  - [A case of splenial astrocytoma with various neuropsychological symptoms].
AB  - A case with splenial astrocytoma that showed various neuropsychological symptoms
      after disappearance of tumor due to chemo- and radiation therapies. A 40-year-old
      right-handed truck driver visited the Neurosurgical Clinic with complaints of
      memory disturbance and loosing his way during truck driving. Under diagnosis of
      protoplasmic astrocytoma chemotherapy and radiation treatments were carried out.
      These treatments were satisfactorily effective, but the patient showed marked
      memory deficits and personality change. He was hospitalized, therefore, into the
      Neuropsychiatric Clinic 20 months after the above mentioned treatments. Aside
      personality changes such as lack of inhibition and shameless acts, the patient
      showed interhemispheric disconnection symptoms (dyslexia in the left visual
      hemifield), memory deficits, and visual perceptual disturbances. His memory
      deficits consisted of anterograde and retrograde amnesia and disorientation of
      time and place, indicating that he had typical amnesic syndrome. In other words
      he had so-called retrosplenial amnesia. His visual perceptual deficits were
      impaired performance on many tasks already described as tests of visual
      perception.

PMID- 8297669
TI  - [Sudden exacerbation in atypical syringomyelia with a unilateral superficial
      sensory disorders as the principal manifestation].
AB  - We report a 22 year-old woman with syringomyelia, who complained of a sudden
      abnormal sensation in the left neck and upper extremity after maintaining her
      neck in flexion for sometime. Neurologic examination revealed superficial
      hypesthesia on the left from C2 down, but normal motor function. The mode of
      onset in our patient was atypical. The clinical manifestations of syringomyelia
      are usually slowly progressive. On the basis of X-P film of the cervical spine
      and cranial MRI, a diagnosis of syringomyelia with Chiari malformation (type 1)
      was made. The syrinx cavity extended from C1 to L1. On the transaxial image of
      the cervical cord, the syrinx cavity was demonstrated in the posterior horn area
      ipsilateral to the sensory disturbance. The CSF flow-void sign was present in the
      syrinx cavity, probably reflecting pulsation of the syrinx fluid. An abnormally
      high signal intensity area adjacent to the syrinx cavity on T2-weighted sequences
      indicated damaged cord. We speculate that dynamic factors produced by neck
      flexion and fluid pulsation explain the sudden exacerbation in our patient.

PMID- 8297670
TI  - [A 79-year-old man with rapidly progressive tetraparesis].
AB  - We report a 79-year-old man who developed progressive gait disturbance and
      sensory loss. He had been doing well except for hepatitis B virus hepatitis until
      72 years of age when he developed angina pectoris for which aorto-coronary bypass
      operation was performed when he was 73-year-old (1986). In 1990, he developed
      pulmonary fibrosis for which prednisolone was prescribed. His liver function
      deteriorated, and the liver function tests suggested liver cirrhosis. He noted an
      onset of gait disturbance in the middle of June in 1992 when he was 79-year-old.
      His gait disturbance deteriorated progressively, and he developed edema and loss
      of sensation in his both legs. He became unable to walk unassisted in the
      beginning of July. He fractured his right external malleolus after falling down
      from a chair. He became unable to stand by himself, and he was admitted to the
      cardiology service of our hospital on July 18, 1992, and the neurology service
      was asked to see the patient on July 30 of the same month. The patient was well
      developed and well nourished man in no acute distress. General physical
      examination revealed slight jaundice, left carotid bruit, and slight pitting
      pretibial edema. His temperature was 37.3 degrees C. On neurologic examination,
      he was alert and mentally sound without dementia. He showed a slight weakness in
      the facial muscles bilaterally and mild dysarthria and dysphagia, however, the
      other cranial nerves appeared intact. He was unable to stand unassisted. The
      muscle tone was hypotonic, however, no focal muscle atrophy was noted, nor was
      observed fasciculatory twitches.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297671
TI  - Saudi sands, SCUDS, and survival.
AB  - SCUD attacks were one of many challenges this pediatric nurse practitioner (NP)
      and Air Force Reserve flight nurse faced daily during Desert Shield and Desert
      Storm. Providing nursing care to sick and injured patients on board a C141
      transport plane en route from Saudi Arabia to Germany was her primary
      responsibility. Additionally, many hours were spent filling sandbags, attending
      in-service classes, and practicing putting on a gas mask and protective suit.
      Although the war has been over for almost 3 years, the effects are long lasting.
      The author was able to use her wartime experience positively to gain insight into
      survival in today's violent society. As violence increases, NPs must reshape
      their focus and educate their clients about survival.

PMID- 8297672
TI  - Ectopic pregnancy.
AB  - Ectopic pregnancy remains a diagnostic and management challenge for nurse
      practitioners. The incidence and physiology of ectopic pregnancy, the current
      research on risk factors, detection methods, and management techniques, and
      counseling strategies are reviewed in this article. In addition, a protocol for
      nurse practitioners to improve the management and possibly lessen the serious
      impact of this challenging complication of pregnancy will be discussed.

PMID- 8297673
TI  - The role of the nurse practitioner in the diagnosis and management of bulimia
      nervosa, Part 3: Psychosocial management.
AB  - Psychological problems associated with bulimia nervosa affect both the client and
      the family. The nurse practitioner is often in a position to refer the client to
      a therapist who has experience in treating clients with eating disorders. The
      nurse practitioner and the therapist, along with the nutritionist, if available,
      need to work from the beginning as a team. Each team member must have a distinct
      role regarding management of specific aspects of client care in order to avoid
      confusion and attempted manipulation by the client.

PMID- 8297674
TI  - Promotion of adaptation in battered women: a self-efficacy approach.
AB  - The purpose of this article is to describe the use of the Self-Efficacy Scale for
      Battered Women (SESFBW) in the development of a treatment plan for the abused
      woman. The authors describe how the SESFBW was developed to assess the self
      efficacy needs of women (N = 43) who came to the emergency department with
      injuries and self-reported current abuse. Four needs related to self-efficacy
      were identified: a decreased ability to (a) talk to the nurse or doctor about the
      abusive situation, (b) call a shelter for abused women, (c) shrug off self
      doubts, and (d) express thoughts and feelings without fear. How data from a self
      efficacy assessment were used in developing a teaching plan and intervention is
      included. Pre- and posttest scores on the SESFBW of six battered women showed a
      significant increase in self-efficacy scores at the completion of a group
      educational program. They conclude that the SESFBW is an easy and effective tool
      to assess self-efficacy and can form the basis for developing an individualized
      teaching plan to increase self-efficacy.

PMID- 8297675
TI  - Knee injuries: collateral ligament sprains.

PMID- 8297676
TI  - Health care reform: consensus is forming to fix the system.

PMID- 8297678
TI  - Stop killing the American worker.

PMID- 8297677
TI  - The learning network: an idea whose time has come.

PMID- 8297679
TI  - Implementing a CQI approach to incident reporting.

PMID- 8297680
TI  - The clinical practice development model: a framework for the recognition of
      nursing practice.

PMID- 8297681
TI  - Complexometric determination of clodronate in aqueous solutions and urine.
AB  - Three different procedures for the determination of clodronate by means of Th
      EDTA-XO or Th-DCTA-XO (XO = xylenol orange) complexes are presented. According to
      the UV-VIS and 13C NMR measurements, XO is quantitatively replaced by the
      clodronate anion in the mixed ligand Th-EDTA-XO or Th-DCTA-XO complexes in
      slightly acidic solutions. This ligand replacement reaction can be applied to the
      determination of traces of clodronate. Procedures studied involve visual
      complexometric titration, spectrophotometric titration and conventional
      spectrophotometric determination. By visual complexometric titration it is
      possible to determine clodronate directly in human urine with acceptable accuracy
      and precision in the range 0.5-2.5 mg l-1. By diluting more concentrated urine
      samples 1:10 with water, samples of up to 80 mg l-1 can be determined with
      acceptable accuracy and precision. The working range of the method is linear up
      to 16 mg l-1 in aqueous solutions with the RSD-value varying between 0.7 and
      3.8%. Interference caused by the major substances of human urine on the
      determination were studied.

PMID- 8297682
TI  - Power spectrum analysis of heart rate variability: a tool to explore neural
      regulatory mechanisms.

PMID- 8297683
TI  - End-on aortogram: improved identification of important coronary artery anomalies
      in tetralogy of Fallot.
AB  - OBJECTIVE: To identify coronary artery anomalies in patients with tetralogy of
      Fallot with an aortogram taken with steep caudal and left oblique angulation
      ("end-on" aortogram). DESIGN: Prospective evaluation of end-on aortogram in the
      preoperative angiographic assessment of consecutive patients with tetralogy of
      Fallot. SETTING: Regional paediatric cardiology centre. PATIENTS: 34 patients,
      aged 3 months to 12 years (median age 9 months). METHODS: An aortogram was
      performed with steep caudal (38 degrees-45 degrees) and left oblique (0 degrees
      30 degrees) angulation under general anaesthetic as part of routine preoperative
      angiographic assessment. RESULTS: The origins and courses of the coronary
      arteries were visualised in all patients and important coronary artery anomalies
      were identified in four patients: single left coronary artery; single right
      coronary artery (two patients); separate high origin of left anterior descending.
      These anomalous coronary vessels crossed the right ventricular outflow tract.
      CONCLUSIONS: It is important to identify preoperatively coronary arteries that
      may interfere with right ventricular outflow tract reconstruction. An aortogram
      with steep caudal and left oblique angulation is useful in identifying anomalous
      coronary arteries and more importantly it defines the relation of these vessels
      to the right ventricular outflow tract.

PMID- 8297684
TI  - Acronym aggravation.

PMID- 8297685
TI  - Monitoring myocardial damage in cardiac surgery by troponin T detection.

PMID- 8297686
TI  - Decreased heart rate variability in survivors of sudden cardiac death not
      associated with coronary artery disease.
AB  - BACKGROUND: Although heart rate variability has already been studied in survivors
      of sudden cardiac death secondary to coronary artery disease, an assessment of
      heart rate variability in survivors of sudden cardiac death not associated with
      coronary artery disease has not been made. METHODS: 10 patients with aborted
      sudden cardiac death not associated with coronary artery disease (seven patients
      with primary ventricular fibrillation and three with unclassified mild
      cardiomyopathy) underwent two channel 24 hour Holter monitoring in a drug free
      state. All subjects were in sinus rhythm and had normal atrioventricular
      conduction and normal cardiac function. Spectral heart rate variability was
      analysed on a Holter analysis system and was expressed as total (0.01-1.00 Hz),
      low (0.04-0.15 Hz) and high (0.15-0.40 Hz) frequency components for each hour.
      Heart rate variability index was calculated for the 24 hour periods. 10 age and
      sex matched healthy subjects were taken as a control group. RESULTS: The spectral
      heart rate variability over 24 hours was significantly lower in survivors of
      sudden cardiac death than in controls (total 38(15) v 48(14) ms; low, 25(11) v
      32(13) ms; and high, 13(8) v 18(8) ms; p < 0.05 for all comparisons). The
      differences in the ratio of low/high (2.19(0.76) v 1.98(0.50), p = 0.132), mean
      heart rate (77(12) v 69(12) beats/min, p = 0.070), and heart rate variability
      index (38(12) v 44(16), p = 0.287) over 24 hours between survivors of sudden
      cardiac death and controls did not reach significance. Comparisons of the hourly
      heart rate variability over the 24 hour period between the two groups showed that
      the differences in all components of heart rate variability, low/high ratio and
      mean heart rate were highly significant. Furthermore, there was no significant
      difference in the maximum hourly heart rate variability over the 24 hour period.
      The minimum hourly heart rate variability was, however, significantly lower in
      survivors of sudden cardiac death than in controls (total, 20(8) v 28(4) ms; low,
      12(6) v 17(3) ms; high, 6(2) v 8(2) ms; p < 0.05 for all comparisons).
      CONCLUSIONS: These findings suggest that there is abnormal autonomic influence on
      the heart in patients without coronary artery disease at risk of sudden cardiac
      death. Hourly analysis of heart rate variability throughout the 24 hour period
      may provide additional information important in the identification of high risk
      patients.

PMID- 8297687
TI  - Differences in autonomic nerve function in patients with silent and symptomatic
      myocardial ischaemia.
AB  - BACKGROUND: Autonomic neuropathy provides a mechanism for the absence of symptoms
      in silent myocardial ischaemia, but characterisation of the type of neuropathy is
      lacking. AIM: To characterise and compare autonomic nerve function in patients
      with silent and symptomatic myocardial ischaemia. METHODS AND RESULTS: The
      Valsalva manoeuvre, heart rate variation (HRV) in response to deep breathing and
      standing, lower body negative pressure, isometric handgrip, and the cold pressor
      test were performed by patients with silent (n = 25) and symptomatic (n = 25)
      ambulatory ischaemia and by controls (n = 21). No difference in parasympathetic
      efferent function between patients with silent and symptomatic ischaemia was
      recorded, but both had significantly less HRV in response to standing than the
      controls (p < 0.005 for silent and p < 0.01 for symptomatic). Patients with
      silent ischaemia showed an increased propensity for peripheral vasodilatation
      compared with symptomatic patients (p < 0.02) and controls (p < 0.04). Impaired
      sympathetic function was found in patients with pure silent ischaemia (n = 4)
      compared with the remaining patients with silent ischaemia whose pain pathways
      were presumed to be intact. CONCLUSIONS: Patients with silent ischaemia and pain
      pathways presumed to be intact have an enhanced peripheral vasodilator response,
      and if this applied to the coronary vasculature it could provide a mechanism for
      limiting ischaemia to below the pain threshold. Patients with pure silent
      ischaemia have evidence of sympathetic autonomic dysfunction.

PMID- 8297688
TI  - Acute pulmonary oedema: an unusual clinical presentation of unruptured sinus of
      Valsalva.

PMID- 8297689
TI  - Heart rate variability and clinical cardiology.

PMID- 8297691
TI  - Differential effect of pharmacological autonomic blockade on some
      electrophysiological properties of the human ventricle and atrium.
AB  - OBJECTIVE: This study investigated the dominance of each limb of the autonomic
      nervous system and tested sympathetic-vagal interactions in the human ventricle
      and atrium after administration of propranolol and atropine. PATIENTS AND
      METHODS: The 90% monophasic action potential duration (MAPD90) and the effective
      refractory period (ERP) at the right ventricular apex (RV) and the right lateral
      atrium (RA) were measured in 14 patients. The MAPD90 was measured during constant
      RV and RA pacing (cycle length 600 ms) and the ERP was measured at a driven cycle
      length of 600 ms. Electrophysiological variables were measured during a control
      period, after propranolol (0.15 mg/kg loading dose followed by 0.1 mg/min
      infusion), and after autonomic blockade (atropine 0.04 mg/kg). RESULTS: Both RV
      MAPD90 and RV ERP increased after propranolol (RV MAPD90 from 268 (26) ms to 275
      (26) ms, p < 0.005; RV ERP from 252 (25) ms to 258 (26) ms, p < 0.0005) and then
      decreased to below the control values after autonomic blockade (RV MAPD90 256
      (24) ms; RV ERP 239 (25) ms, p < 0.0005 v propranolol, p < 0.0005 v control). In
      contrast, both RA MAPD90 and RA ERP increased after propranolol (RA MAPD90 from
      242 (19) ms to 260 (19) ms; RA ERP from 216 (21) ms to 230 (18) ms, p < 0.0005),
      and then increased slightly more after autonomic blockade (RA MAPD90 265 (16) ms,
      p = 0.09; RA ERP 235 (16) ms, p = 0.07), thus remaining above control values (p <
      0.0005). CONCLUSIONS: The results indicate (a) that in the human ventricle vagal
      stimulation and sympathetic beta stimulation are antagonistic and that direct
      vagal stimulation predominates over beta stimulation, with sympathetic-vagal
      interaction being minimal and (b) that in the human atrium vagal stimulation and
      beta stimulation are synergistic and beta stimulation predominates over vagal
      stimulation, with direct vagal stimulation having a minimal effect.

PMID- 8297690
TI  - Angiotensin converting enzyme inhibition in chronic stable angina: effects on
      myocardial ischaemia and comparison with nifedipine.
AB  - OBJECTIVES: To determine the anti-ischaemic effects of a new angiotensin
      converting enzyme inhibitor, benazepril, compared with nifedipine, alone and in
      combination, in chronic stable angina caused by coronary artery disease. DESIGN:
      Placebo controlled, double blind, latin square design. SETTING: Regional
      cardiology service for a mixed urban and rural population. SUBJECTS: 40 patients
      with stable exertional angina producing at least 1 mm ST segment depression on
      exercise test with the Bruce protocol. 34 patients completed all four phases of
      the trial. INTERVENTIONS: Each patient was treated with placebo, benazepril (10
      mg twice daily), nifedipine retard (20 mg twice daily), and a combination of
      benazepril and nifedipine in the same doses, in random order for periods of two
      weeks. MAIN OUTCOME MEASURES AND RESULTS: Total duration of exercise was not
      increased by any treatment. Exercise time to the development of 1 mm ST segment
      depression was not significantly changed with benazepril alone or in combination
      with nifedipine but was increased with nifedipine from 4.18 (1.8) min to 4.99
      (1.6) min (95% confidence interval (95% CI) 0.28 to 1.34; p < 0.05). There was a
      significant relation between increase in duration of exercise and resting renin
      concentration (r = 0.498; p < 0.01). Myocardial ischaemia during daily activity,
      as assessed by ambulatory electrocardiographic monitoring, was reduced by
      benazepril and by the benazepril and nifedipine combination. This was significant
      for total ischaemic burden (451(628) min v 231(408) min; 95% CI -398 to -41 min;
      p < 0.05) and maximal depth of ST segment depression (-2.47(1.2) mm v -2.16 mm;
      95% CI 0.04 to 0.57; p < 0.05) for the combination and for maximal ST segment
      depth for benazepril monotherapy (-2.47 (1.2) mm v -1.96(1.2) mm; 95% CI 0.18 to
      0.91; p < 0.05). Benazepril significantly altered the circadian rhythm of cardiac
      ischaemia, abolishing the peak ischaemic periods at 0700 to 1200 and 1700 to 2300
      (p < 0.05). CONCLUSIONS: Benazepril, an angiotensin converting enzyme inhibitor,
      had a modest anti-ischaemic effect in effort angina, but this effect was not as
      pronounced as with nifedipine. The anti-ischaemic action was more noticeable in
      asymptomatic ischaemia during daily activity, whereas nifedipine had little
      effect on this aspect of myocardial ischaemia. The combination of benazepril and
      nifedipine reduced ischaemia of daily activity.

PMID- 8297692
TI  - Implication of prescriptions for nitrates: 7 year follow up of patients treated
      for angina in general practice.
AB  - OBJECTIVE: To determine the demand placed on local cardiological services by
      patients prescribed nitrates for ischaemic heart disease. DESIGN: A follow up
      study of a cohort of patients identified in 1985. SETTING: Nottingham Health
      District. PATIENTS: Four hundred and ninety nine patients prescribed nitrates in
      1985 for presumed ischaemic heart disease. MAIN OUTCOME MEASURES: Referral to
      medical outpatients, admittance to hospital with chest pain, cardiological
      investigations, and mortality. RESULTS: Over the seven year period 26% of
      patients were admitted urgently with chest pain and 15% were referred to the
      medical outpatient department--a referral rate of 6% a year. 4% of patients had
      an exercise test and 6% a coronary angiogram. The death rate was 6% a year and a
      higher proportion died of cardiovascular causes than would be expected in the
      general population. CONCLUSIONS: Prescription of nitrate is useful in the
      determination of the prevalence of ischaemic heart disease. Most patients with
      angina are still treated within the community, and the rate of specialist
      investigation remains low.

PMID- 8297693
TI  - Insulin resistance syndrome as a feature of cardiological syndrome X in non-obese
      men.
AB  - OBJECTIVE: To assess the features of the insulin resistance syndrome in patients
      presenting with cardiological syndrome X, who experience angina despite
      angiographically normal coronary arteries. PATIENTS AND METHODS: 14 Non-obese
      male patients with syndrome X and 38 symptom free, apparently healthy, male
      volunteers were studied. Insulin sensitivity (inversely related to insulin
      resistance) was measured by minimal modelling analysis of glucose and insulin
      concentrations during an intravenous glucose tolerance test. Serum lipids,
      lipoproteins, and apolipoproteins were also measured. RESULTS: Insulin
      sensitivity was 31% lower in the men with syndrome X (p < 0.05) and fasting
      insulin concentration was 30% higher (p < 0.05). The patient group also had 64%
      higher mean triglycerides (p < 0.001) and 20% lower mean high density lipoprotein
      cholesterol concentration (p < 0.01). Systolic blood pressure was also 10% higher
      in the syndrome X group (p < 0.01). There were no differences in total
      cholesterol, low density lipoprotein cholesterol or lipoprotein (a). CONCLUSION:
      These findings show that non-obese male patients with anginal chest pain but
      normal coronary arteries (syndrome X) are insulin resistant, hyperinsulinaemic,
      and have higher concentrations of triglycerides and lower high density
      lipoprotein cholesterol than healthy men. The insulin resistance syndrome may
      predispose to a spectrum of arterial disease capable of causing myocardial
      ischaemia.

PMID- 8297694
TI  - Is thickening of the basal lamina in the saphenous vein a hallmark of smoking?
AB  - OBJECTIVE: To investigate whether smoking causes ultrastructural changes in the
      intima of the proximal saphenous vein. DESIGN: Proximal saphenous veins from
      heavy smokers and non-smokers were examined with scanning and transmission
      electron microscopy to determine changes in surface ultrastructure, in the
      intercellular junction, and in the thickness of the basal lamina. Immunogold
      labelling was used to identify specific components of the endothelial basal
      lamina. MATERIAL: Vein specimens were obtained from patients undergoing varicose
      vein surgery (12 patients) or distal bypass surgery (eight patients). MAIN
      RESULTS: The only ultrastructural change that discriminated between specimens was
      thickening of the endothelial basal lamina. All specimens with a thickened basal
      lamina were from heavy smokers. Immunogold labelling studies showed that the
      thickened basal lamina contained specific accumulations of fibronectin but not
      heparan sulphate proteoglycans, type IV collagen, or laminin. CONCLUSIONS: Two
      ultrastructural characteristics are associated with smoking: thickening of the
      endothelial basal lamina and a specific accumulation of fibronectin in the
      thickened basal lamina. Such abnormalities in the saphenous veins from smokers
      may contribute to the poorer performance of these veins as bypass conduits.

PMID- 8297695
TI  - Mitral valve repair: a clinical and echocardiographic study.
AB  - OBJECTIVE: To evaluate the clinical and echocardiographic results of mitral valve
      repair done within an 11 year period. DESIGN: Retrospective review of case notes
      and clinical and echocardiographic examination of survivors. Analysis was made
      according to the intention to treat principle. PATIENTS: A consecutive series of
      94 patients with mitral valve disease who had mitral reconstruction between 1980
      and 1991. INTERVENTIONS: Mitral repair according to the techniques of Carpentier
      or Duran. MAIN OUTCOME MEASURES: Operative mortality, actuarial survival, rates
      of freedom from reoperation, thromboembolism, infective endocarditis, clinical
      state, and echocardiographic findings. RESULTS: There were equal numbers of males
      and females (mean (range) age 49 (4-74) years). The aetiology of mitral disease
      was degenerative in 59% and rheumatic in 30% of the patients. Operative mortality
      was 3%. The 10 year actuarial and valve related survival rates were 67% and 75%.
      At 10 years, 84% of the patients were free from thromboembolism, 94% free from
      haemorrhage related to anticoagulation, 88% free from infective endocarditis, and
      73% free from reoperation. Of 75 survivors with completed follow up, 96% were in
      New York Heart Association functional class I or II and 64% were in sinus rhythm.
      Of 55 survivors who had an echocardiogram at follow up, normal left ventricular
      end diastolic dimension was shown in 76% and normal left ventricular shortening
      fraction in 89%. Doppler studies showed no mitral regurgitation in 36%, trivial
      or mild in 42%, moderate in 14%, and severe in 7% of patients. In stepwise
      logistic analysis previous myocardial infarction was associated with poor outcome
      (odds ratio: 13.7, p < 0.05). CONCLUSION: The results are comparable with similar
      studies and support the value of mitral valve repair. There is reservation about
      the use of repair for patients with previous myocardial infarction.

PMID- 8297696
TI  - Profiles of coronary blood flow velocity in patients with aortic stenosis and the
      effect of valve replacement: a transthoracic echocardiographic study.
AB  - OBJECTIVE: To report the first non-invasive assessment by transthoracic Doppler
      echocardiography of coronary blood flow in patients with aortic stenosis and of
      the effects of valve replacement. DESIGN: High frequency transthoracic Doppler
      echocardiography was used to examine resting phasic flow in the left anterior
      descending coronary artery before and after replacement of the aortic valve in
      awake, unsedated patients with pure aortic stenosis and normal coronary arteries.
      SETTING: A tertiary referral cardiothoracic centre. METHODS: Eleven patients with
      pure aortic stenosis and normal coronary arteries (six men, five women, mean
      (range) age 69 (50-82) years), were studied the day before and 1 week after
      replacement of the aortic valve. These patients were selected from a cohort of 15
      due to ease of imaging of the left anterior descending coronary artery. Seven had
      a history of angina. Haemodynamics, peak transvalvar aortic gradient, left
      ventricular mass index, ventricular dimensions, and profiles of coronary flow
      velocity were measured. Profiles of coronary flow velocity were also measured in
      a control population of 10 normal subjects (five men, five women, mean (range)
      age 58 (34-66) years). RESULTS: The control population showed forward flow
      throughout systole, but reversed early systolic flow (mean velocity 20.6 (3.6)
      cm/s) was seen in six patients with aortic stenosis. Only three of these patients
      had a clinical history of angina. Peak and mean systolic and diastolic forward
      flow velocities were not significantly different in the control group and in
      patients with aortic stenosis. The time from the start of systole to the onset of
      forward systolic flow was significantly longer in patients with aortic stenosis
      than in the control population (185 (8.5) v 85 (10) ms, p < 0.01). The time from
      the onset of diastolic flow to peak diastolic velocity was also significantly
      longer in the aortic stenosis group (146 (16) v 74 (13) ms, p < 0.01). These
      abnormalities in profiles of coronary flow were reversed by replacement of the
      aortic valve. There was no correlation between changes in flow profiles in
      patients with aortic stenosis and preoperative clinical history, transvalvar
      gradient, left ventricular mass index, or ventricular dimensions. CONCLUSIONS:
      Coronary flow profiles in patients with aortic stenosis were characterised by
      reversed early systolic flow and delayed forward systolic flow and attainment of
      peak diastolic velocity. Reversal of these abnormalities by replacement of the
      aortic valve may reflect altered left ventricular and aortic haemodynamics and
      contribute to the relief of angina when left ventricular hypertrophy persists.
      Further studies may correlate abnormalities of coronary flow with preoperative
      clinical and haemodynamic state.

PMID- 8297697
TI  - Papillary fibroelastoma of the mitral valve: a rare cause of transient
      neurological deficits.

PMID- 8297698
TI  - Medium-term follow up of residual shunting and potential complications after
      transcatheter occlusion of the ductus arteriosus.
AB  - OBJECTIVES: To determine the causes and outcome of residual shunting after
      transcatheter occlusion of persistent ductus arteriosus with the Rashkind double
      umbrella occluder, and to determine the potential of the device to produce
      obstruction to flow in the aorta and left pulmonary artery. DESIGN: Angiographic
      examination of morphology of ductus followed by prospective clinical and
      ultrasound evaluation (including cross sectional imaging, colour flow mapping,
      and pulse wave Doppler) of all patients undergoing occlusion of persistent ductus
      arteriosus between October 1987 and July 1992. PATIENTS: 140 patients with ages
      between 0.5 and 78 (median 3.8) years and weights between 6.8 and 74 (median
      13.8) kg. INTERVENTIONS: Attempted implantation of the Rashkind double umbrella
      ductus occluder under angiographic control through a transvenous (n = 136) or
      transarterial (n = 4) approach. MAIN OUTCOME MEASURES: Successful occlusion of
      ductus; frequency, pattern, and prognosis of residual shunts; Doppler velocities
      in left pulmonary artery and aorta; volume loading of the left heart. RESULTS:
      Including reocclusions the overall rate of successful occlusion was 96%. A total
      of six devices embolised at the time of operation (4.3%) with no sequelae. There
      were no anatomical factors that predicted a poor outcome, but suboptimal
      positioning of the device led to a significantly higher incidence of residual
      shunts (p < 0.001). Colour flow mapping correctly identified shunts that were
      unlikely to close spontaneously (n = 9) and to date seven have undergone
      successful closure with a second device. Encroachment of device legs produced
      statistically (p < 0.001) but not clinically significant increases in left
      pulmonary artery Doppler velocities that diminished with time. CONCLUSIONS:
      Transcatheter occlusion provides a safe and effective means of closing a
      persistent ductus arteriosus. Doppler colour flow mapping is necessary for follow
      up and shows those ducts requiring reocclusion. The device did not produce
      significant disturbance to flow in the pulmonary arteries or aorta.

PMID- 8297699
TI  - Failure of epoprostenol (prostacyclin, PGI2) to inhibit platelet aggregation and
      to prevent restenosis after coronary angioplasty: results of a randomised placebo
      controlled trial.
AB  - OBJECTIVE: To study the effect of epoprostenol (prostacyclin, PGI2) given before,
      during, and for 36 h after coronary angioplasty on restenosis at six months and
      to evaluate the transcardiac gradient of platelet aggregation before and after
      percutaneous transluminal coronary angioplasty (PTCA) in treated and placebo
      groups. DESIGN: Double blind placebo controlled randomised study. PATIENTS: 135
      patients with successful coronary angioplasty. METHODS: Intravenous infusion of
      PGI2 (4 ng/kg/ml) or buffer was started before balloon angioplasty and continued
      for 36 hours. Platelet aggregation was measured in blood from the aorta and
      coronary sinus before and after PTCA in each group. Routine follow up was at six
      months with repeat angiography and there was quantitative assessment of all
      angiograms (those undertaken within the follow up period and at routine follow
      up). PRESENTATION OF RESULTS: Restenosis rates in treated and placebo groups
      determined according to the National Heart, Lung and Blood Institute definition
      IV. Comparison at follow up between the effect of treatment on mean absolute
      luminal diameter and mean absolute follow up diameter in the placebo group.
      Comparison of acute gain and late loss between groups. RESULTS: Of 125 patients
      available for assessment 23 were re-admitted because of angina within the follow
      up period. Quantitative angiography showed restenosis in 15 (10 in the PGI2 group
      and five in the placebo group). Of 105 patients evaluated at six month
      angiography there was restenosis in nine more in the PGI2 group and 18 more in
      the placebo group. Total restenosis rates (for patients) were 29.2% for PGI2 and
      38.3% for placebo (NS). The mean absolute gain in luminal diameter was 1.84
      (0.76) mm in the PGI2 group and 1.58 (0.56) mm in the placebo group (p = 0.04);
      the late loss in the PGI2 group was also greater (0.65 (0.94) mm vs 0.62 (0.89)
      mm (NS) and there was no significant difference in final luminal diameter at
      follow up between the two groups (1.83 (0.88) mm v 1.59 (0.60) mm). The
      transcardiac gradient of quantitative platelet aggregation increased after PTCA
      in both groups, indicating that PGI2 in this dose did not affect angioplasty
      induced platelet activation. Mean (SD) platelet activation indices in the PGI2
      group were pre PTCA aorta 8.4 (4.1) v coronary sinus 8.8 (4.0) (p = 0.001) and
      post PTCA aorta 8.9(3.0) v coronary sinus 12.9 (5.7) (p = 0.001). In the placebo
      group the values were pre PTCA aorta 7.6 (3.3) v coronary sinus 7.4 (3.6) (p =
      0.001) and post PTCA aorta 7.6(2.8) v coronary sinus 11.2(4.3) (p = 0.001).
      CONCLUSION: The dose of PGI2 given was designed to limit side effects and as a
      short-term infusion did not significantly decrease the six month restenosis rate
      after PTCA. The sample size, which was determined by the original protocol and
      chosen because of the potency of the agent being tested, would have detected only
      a 50% reduction in restenosis rate. There was, however, no effect in the treated
      patients on the increased platelet aggregation seen in placebo group as a result
      of angioplasty. Angioplasty is a powerful stimulus to blood factor activation.
      Powerful agents that prevent local platelet adhesion and aggregation are likely
      to be required to reduce restenosis.

PMID- 8297700
TI  - Coarctation of the aorta: difficulties in prenatal diagnosis.
AB  - OBJECTIVE: To formulate echocardiographic criteria for the prenatal diagnosis of
      coarctation of the aorta. DESIGN: A retrospective study examining the
      echocardiograms of fetuses with a verified aortic arch abnormality and those in
      whom the diagnosis was suspected prenatally but was not subsequently confirmed.
      SETTING: Tertiary referral centre for fetal echocardiography. PATIENTS: 87
      fetuses in whom the diagnosis of coarctation was correctly made in 54, suspected
      but unproved in 24, and overlooked prenatally in nine. MAIN OUTCOME MEASURES:
      Measurements of left and right ventricular size, the diameters of the great
      arteries, the diameters of the left and right atrioventricular valvar orifices,
      the appearance of the aortic arch, and the direction of the flow of blood across
      the foramen ovale. RESULTS: Measurements of the ventricular widths, diameters of
      the great arteries, or the diameters of the atrioventricular valvar orifices, did
      not allow clear distinction between cases that definitely had a coarctation and
      those in whom the diagnosis was unproved. The appearance of the aortic arch,
      particularly in the horizontal projection, was more helpful in distinguishing
      cases of coarctation, although this also was not always diagnostic. A
      predominantly left to right shunt across the foramen ovale was detected more
      often in cases with a substantiated coarctation (58%) than in those with an
      unproved diagnosis (12%). CONCLUSIONS: The most severe forms of coarctation are
      associated with relative hypoplasia of the left heart structures compared with
      the right and a correct diagnosis can be made in early pregnancy. The milder
      forms of coarctation, however, are consistent with a normal early fetal
      echocardiogram. In late pregnancy it may be impossible to exclude coarctation
      categorically as the right heart structures may appear larger than the left in
      the normal fetus. Thus although a combination of echocardiographic features can
      correctly identify aortic arch anomalies in the fetus, none either alone or in
      combination, could clearly distinguish between real and false positive cases,
      particularly in late gestation.

PMID- 8297701
TI  - Do specific HLA antigens predispose to ischaemic heart disease or idiopathic
      dilated cardiomyopathy?
AB  - BACKGROUND: The aetiology of idiopathic dilated cardiomyopathy is believed to
      have an immunological component. Association with human leucocyte antigens (HLAs)
      has been previously reported, particularly with HLA-DR4. AIM: To determine the
      association of HLA type with diagnosis in a group of patients assessed for heart
      transplantation. METHODS: A comparison was made of frequencies of HLA types in
      patients with a diagnosis of idiopathic dilated cardiomyopathy or (n = 98)
      ischaemic heart disease (n = 170) and in controls from the North Western region
      (n = 857). RESULTS: Neither the patients with idiopathic dilated cardiomyopathy
      nor those with ischaemic heart disease showed a significant increase or decrease
      in any HLA frequency compared with the controls. CONCLUSION: These results
      suggest that there is no HLA association with idiopathic dilated cardiomyopathy
      or ischaemic heart disease. This conflicts with the results of some previous
      studies.

PMID- 8297702
TI  - Familial atrioventricular septal defect: possible genetic mechanisms.
AB  - BACKGROUND: Most non-chromosomal congenital heart defects are thought to be
      caused by the interaction of genetic factors involving multiple genes and
      environmental factors. Families that have several affected members have been
      reported, however, which suggests that a single autosomal dominant or recessive
      gene may cause the cardiac defects. A family in which atrioventricular septal
      defect seemed to be a single gene disorder is reported. OBSERVATIONS: A family in
      which the mother and her two daughters from different fathers had
      atrioventricular septal defect not associated with trisomy 21 is reported.
      CONCLUSIONS: This family raises the possibility that cytoplasmic or mitochondrial
      inheritance may be involved in the causation of atrioventricular septal defects.
      The available data from pedigrees from other cases of familial atrioventricular
      septal defect do not support this genetic mechanism, but suggest that there is a
      subgroup without trisomy 21 that has a single gene disorder.

PMID- 8297703
TI  - Wegener's granulomatosis and the heart.
AB  - Three cases of Wegener's granulomatosis with cardiac complications are described
      and the relevant published reports are reviewed. The first case of Wegener's
      granulomatosis was associated with aortic regurgitation and required aortic valve
      replacement. The second and third cases were associated with pericardial disease
      requiring pericardiectomy for constructive pericarditis in one case, and
      haemorrhagic pericarditis with pericardial effusion in the other. Aortic valve
      involvement in Wegener's granulomatosis is uncommon and valve replacement has
      been described on only one previous occasion. Pericardial involvement is
      relatively common pathologically, but pericardial surgery has been described in
      this condition only twice, once for tamponade and once for constrictive
      pericarditis after pericardiocentesis. Cardiac involvement is not uncommon in
      patients with Wegner's granulomatosis and may be clinically important. Diagnosis
      is aided by estimation of the anti-neutophil cytoplasmic antibody titre.

PMID- 8297704
TI  - Progressive reduction of heart rate variability with eventual sudden death in two
      patients.
AB  - In two patients with old myocardial infarction and congestive heart failure there
      was a progressive reduction of heart rate variability and eventual sudden death.
      The two patients had had three 24 h electrocardiogram recordings within two years
      of death. The power of two spectral bands was calculated-0.04-0.15 Hz, low
      frequency power, and 0.15-0.40 Hz, high frequency power. The mean low and high
      frequency powers over the 24 h recording progressively decreased whereas the
      frequency of ventricular arrhythmias showed no consistent changes in either
      patient. The circadian variation in hourly low and high frequency powers in the
      last 24 h electrocardiogram recordings was much reduced. These results suggest
      that sequential measurements of heart rate variability may be useful in
      predicting sudden death.

PMID- 8297705
TI  - Maldevelopment of conotruncal and aorto-pulmonary septum with absent left central
      pulmonary artery: anatomical and clinical implications.
AB  - In a patient with pulmonary valve atresia with hypoplastic main pulmonary artery
      selective angiography showed absence of the central left pulmonary artery and a
      right pulmonary artery originating from the ascending aorta close to the left
      coronary artery. This unusual anatomical arrangement complicates interventional
      and surgical treatment.

PMID- 8297706
TI  - Treatment of atrial fibrillation in a district general hospital.
AB  - OBJECTIVE: To assess current strategies used to investigate and manage acute
      atrial fibrillation in hospital. DESIGN: Prospective survey of all acute
      admissions over 6 months. SETTING: District general hospital serving a population
      of 230,000 in north east Glasgow. SUBJECTS: 2686 patients admitted as emergency
      cases over 6 months. RESULTS: Of the 2686 patients, 170 (age range 38-95, mean
      (SD) 73.5 (10.6) years; 70 men (41%) and 100 women (59%)) were admitted with
      atrial fibrillation. The principal underlying medical conditions were ischaemic
      heart disease in 79 (46.5%), rheumatic heart disease in 26 (15.3%), and thyroid
      disease in six (3.5%). Cardiac failure was present on admission in 61 (36%),
      cerebrovascular events in 23 (14%), and myocardial infarction in 17 (10%). Of
      those with a history of atrial fibrillation (102 (60%) including 10 with
      paroxysmal atrial fibrillation) treatment on admission included digoxin in 71
      (70%), warfarin in 20 (20%), and aspirin in 17 (17%); the aspirin was
      predominantly given for concomitant vascular disease. The mean (SD) inpatient
      stay was 16 days (19.7) (range 1-154) largely due to the patients with stroke.
      Thyroid function tests were performed in only 63% and echocardiography in 33%.
      Overall, the rate of introduction of anticoagulation (seven patients) and
      attempted cardioversion (21 patient: 19 pharmacological and two electrical) was
      surprisingly low. Only 49 patients (34% of those not on warfarin) had
      contraindications to anticoagulation: these included peptic ulcer or
      gastrointestinal bleeding in 18 (12%), dementia in eight (6%), chronic renal
      failure or dialysis in eight (6%), and alcohol excess in four (3%). CONCLUSION:
      Standard investigations were inadequately used in patients with atrial
      fibrillation and there was a reluctance to perform cardioversion or to start
      anticoagulant treatment.

PMID- 8297707
TI  - Survey of the attitudes of British physicians to pacing.
AB  - OBJECTIVES: To assess how the opinions of cardiologists, physicians, and general
      practitioners on the indications for permanent pacing compare with published
      guidelines, and to determine whether resources, pacing experience, and position
      influence referral practices. DESIGN: Anonymous postal survey by questionnaire
      from St Bartholomew's Hospital, London and the King's Fund Institute, London. The
      questionnaire established the respondent's position, resources, and previous
      pacing experience. Eleven clinical and electrocardiographic situations were
      described and respondents were asked to decide on whether pacing was indicated.
      The responses received were compared with the guidelines provided by the 1984
      American College of Cardiology/American Heart Association task force.
      PARTICIPANTS: The 630 members of the British Cardiac Society, 1370 randomly
      selected general physicians, and 2000 general practitioners. RESULTS: Patients
      with symptoms were more likely to be referred for pacing than symptom free
      patients regardless of underlying aetiology. In relatively symptom free patients
      the frequency with which pacing was recommended was low, even when it was
      unequivocally indicated on prognostic grounds. Failure to recommend pacing was
      unrelated to diagnostic facilities or referral difficulties. Respondents with
      pacing experience were more likely to recommend pacing. CONCLUSIONS: The
      physicians surveyed had a conservative approach towards recommending pacing. Most
      physicians were influenced predominantly by symptoms and the prognostic
      indications for pacing were not well appreciated.

PMID- 8297708
TI  - Safe sex? Misconceptions, gender differences and barriers among injection drug
      users: a focus group approach.
AB  - Heterosexual transmission is one factor involved in the spread of the human
      immunodeficiency virus (HIV) within the injection drug use (IDU) population and
      between IDU and non-IDU individuals. Insufficient information is currently
      available to reduce this heterosexual transmission. As a basis for designing a
      questionnaire aimed at the IDU population, we conducted 5 focus groups to collect
      information on knowledge of and attitudes toward safe sex as held by male and
      female IDUs in methadone treatment. We identified misconceptions related to HIV
      infection, condoms, and sexual behavior. We also found gender-based differences
      in knowledge and learning style. Also, while individuals felt a responsibility to
      prevent HIV transmission, they lacked sufficient control to do so. The wide range
      of responses on questions concerning sexually transmitted diseases (STDs),
      condoms, reproductive decisions, and methods of promoting safe sex provides a
      basis for developing a questionnaire designed to identify and target specific
      subgroups for educational intervention.

PMID- 8297709
TI  - Unsafe sex: decision-making biases and heuristics.
AB  - This paper suggests that continued high-risk behavior is the result of the
      heuristics used to make judgments under uncertainty, and that the same heuristics
      may be mobilized to increase the use of safer-sex practices. In order to explain
      why it is that individuals fail to make effective use of the information they may
      have concerning rates of infection, consequences of infection and their own at
      risk status, theory and research in several areas will be considered.
      Developments in the breadth of areas to which basic research on decision-making
      has been applied continue to provide new approaches toward understanding and
      overcoming the processes by which we reason (Kahnemann, 1991). It is worth
      reminding ourselves that public health campaigns in other areas have led to
      changes in behavior. Reasoning, even with its biases, is still the route by which
      we make decisions, most of them effective and self-protective.

PMID- 8297710
TI  - AIDS-related reasons for gay men's adoption of celibacy.
AB  - Since it was first recognized that human immunodeficiency virus (HIV) infection
      could be sexually transmitted, celibacy has been advocated by some as the only
      unequivocally effective adaptation for avoiding the risk of infection. Others,
      however, have countered that few will be willing to be celibate and, further,
      that such behavior may have adverse psychosocial consequences. As part of a
      qualitative study of gay men's sexual decision-making in the context of the
      AIDS/HIV epidemic, we identified a subsample of respondents who had adopted
      celibacy for varying periods of time as an adaptation to the threat of AIDS/HIV
      infection. A content analysis of these men's interviews revealed 5 principal
      themes relating their reasons for choosing celibacy.

PMID- 8297711
TI  - Gender differences in AIDS-relevant condom attitudes and condom use.
AB  - Two studies, conducted approximately one year apart, examined gender differences
      in AIDS-relevant condom attitudes, condom use behaviors, and relationships among
      attitudes and condom use behaviors. Subjects (N = 248, N = 528) were
      undergraduates, primarily heterosexual. Females reported more favorable
      attitudes, with the exception of greater inhibition about buying and possessing
      condoms. Men engaged in preliminary condom use behaviors (carrying and keeping
      condoms at home) substantially more often than did women. Preliminary condom use
      behaviors predicted past and intended condom use more consistently for men than
      for women. Relationships between condom attitudes and condom use behaviors were
      generally similar for both sexes, with poorer self-control explaining the most
      variance in past and intended condom use. These results, interpreted from the
      perspective of Eagly's (1987) gender role theory, suggest that although females
      may indirectly influence condom use decisions, providing condoms is the expected
      role of males, infusing them with greater control over the interpersonal process.

PMID- 8297712
TI  - An evaluation of a school-based AIDS/HIV education program for young adolescents.
AB  - This study evaluated the efficacy of a school-based AIDS/human immunodeficiency
      virus (HIV) education program on 6th and 7th grade students. Using a quasi
      experimental pretest-posttest control group design, a control group and an
      education group (intervention I) received both pretest and posttest
      questionnaires and a second education group (intervention II) was posttested
      only. Students were evaluated using a modified version of the Centers for Disease
      Control's Health Risk Survey. Students who received AIDS education were less
      likely (p < or = 0.0001) than the control group to report that they had changed
      their behavior to avoid getting AIDS, but thought they had a greater (p < or =
      0.0002) chance of acquiring AIDS as an adult. In the intervention I group, males
      who had never received prior AIDS instruction were more worried about acquiring
      AIDS as an adult (p < or = 0.013). In the intervention II group, the education
      had a significant impact on the level of knowledge about AIDS/HIV infection (p <
      or = 0.0003) and the degree of tolerance toward students with AIDS (p < or =
      0.0008), but the effect was not greater than the learning that occurred in the
      other 2 groups from testing alone. Students who were pretested were also less
      worried that they had been exposed to AIDS (p < or = 0.0001), more worried that
      they would die if they acquired AIDS (p < or = 0.05), and less likely to think
      AIDS patients should be isolated (p < or = 0.0005). Although this AIDS education
      program appeared to be moderately successful in this group of younger
      adolescents, significant learning also occurred fro testing alone.

PMID- 8297713
TI  - Young adolescent attitudes toward sex and substance use: implications for AIDS
      prevention.
AB  - This paper explores differences in adolescents' attitudes, beliefs, and
      resistance skills regarding sexual behaviors and use of substances in the context
      of AIDS prevention. A total of 553 7th and 8th grade students completed a self
      administered questionnaire as baseline data collection for a human
      immunodeficiency virus (HIV) prevention project. Students' attitudes about sexual
      behavior and substance use differed markedly. Teens in this sample reported
      feeling significantly more comfortable discussing substance use with their
      parents than discussing sex; they also reported that it is easier to say "no" to
      alcohol or marijuana than to resist pressures to have sex. Furthermore, these
      young adolescents believed that their parents would be less upset to discover
      that they were sexually active than to find out they were using drugs. Among
      students who had ever had sex and who had ever used alcohol, young adolescents
      indicated that their parents would be much less upset to find out they were
      having sex than to discover they were smoking, drinking alcohol, or using drugs.
      Implications of the findings for HIV/AIDS prevention efforts are discussed.

PMID- 8297714
TI  - Social network, support and influence: relationships with drug use and protective
      AIDS behavior.
AB  - One reason for difficulty in long-term maintenance of behavior changes by
      injection drug users (IDUs) is the concomitant support or distraction from the
      IDUs social environment. This study explored the relationship of social factors-
      e.g., encouragement from friends, beliefs about social norms--with drug injection
      behaviors. Subjects were clients in a short-term residential detoxification
      program. Self-reports of drug and AIDS-protective behaviors were gathered at
      baseline and at least 6 months following a trial of enhanced vs. informational
      educational interventions. Results provide support both for the general
      hypothesis about the influence of peers and drug-use partners prior and
      subsequent to detoxification and for the greater effectiveness of the enhanced
      intervention on social factors. Particularly important to improved drug use
      behavior were decreased number of friends who inject drugs (social network),
      increased number of people to talk with when upset (social support), and
      increased argument skills about safe drug use (social influence).

PMID- 8297715
TI  - Mechanism of cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian
      carcinoma cells in vitro and modulation of the drug activity by folic or folinic
      acid.
AB  - Inhibition of clonogenic potential by the glycinamideribonucleosyl transformylase
      inhibitor 5,10-dideazatetrahydrofolic acid (DDATHF, Lometrexol) was evaluated in
      vitro in a human ovarian carcinoma cell line, SW626. Drug-induced inhibition of
      clonogenic potential is a function of the dose and time of exposure and is
      independent of the formation of DNA single-strand breaks or de novo synthesis of
      protein. Simultaneous treatment with 100 microM hypoxanthine completely prevented
      the inhibition of clonogenic potential caused by 0.5 microM DDATHF. DDATHF
      blocked cells in the early-middle S-phases of the cell cycle, and there was a
      corresponding marked reduction in the rate of DNA synthesis after drug
      withdrawal. The cytotoxic potential of DDATHF was modulated by the folic acid
      concentration present in the medium. In a medium containing 0.22 microM folic
      acid, DDATHF cytotoxicity was at least 100 times that in a regular medium
      containing 2.22 microM folic acid, levels which, however, are about 100 times
      those found in human plasma. DDATHF cytotoxicity differed moderately when folic
      acid concentrations varied between 0.22 and 0 microM, suggesting that folic acid
      does not necessarily antagonise DDATHF anti-tumour activity. Folinic acid at a
      concentration as low as 0.1 microM can completely rescue cells when given
      simultaneously with 0.5 microM DDATHF. When folinic acid was given 24 h after
      DDATHF, a reversal of cytotoxicity was observed at 0.5 and 1 microM, but to a
      much lesser extent than simultaneous treatment. When folinic acid was added after
      48 or 72 h of DDATHF washout, even at a high concentration and for a long time,
      no reduction in DDATHF cytotoxicity was found. In conclusion, the study
      highlights the modulation of DDATHF cytotoxicity by folic acid or by folinic acid
      and provides further rationale for in vivo clinical investigation with these
      combinations.

PMID- 8297716
TI  - Cytostatic inhibition of endothelial cell growth by the angiogenesis inhibitor
      TNP-470 (AGM-1470).
AB  - Recently, we reported the anti-angiogenic action along with anti-tumour activity
      of TNP-470 (AGM-1470). In this study, the effect of TNP-470 on the growth of
      human umbilical vein endothelial (HUVE) cells was examined. TNP-470 inhibited the
      growth of HUVE cells in a biphasic manner. The inhibition was cytostatic in the
      first phase (complete inhibition at 300 pg ml-1 to 3 micrograms ml-1 with an IC50
      of 15 pg ml-1) and cytotoxic in the second phase (> or = 30 micrograms ml-1). The
      cytostatic inhibition of HUVE cell growth by TNP-470 was durable after washing
      out TNP-470 in culture. Incorporation of thymidine but not uridine and leucine by
      HUVE cells was inhibited in the first phase, while that of all three compounds
      was inhibited in the second phase. Human and rat endothelial cells among various
      types of cells were the most sensitive to the cytostatic inhibition, while
      differences in the cytotoxic inhibition were minimal. These results suggest that
      TNP-470 exerts its specific anti-angiogenic action by inhibiting cytostatically
      growth of endothelial cells in a relatively specific manner.

PMID- 8297717
TI  - Enhancement of sensitivity to platinum(II)-containing drugs by 12-O-tetradecanoyl
      phorbol-13-acetate in a human ovarian carcinoma cell line.
AB  - Sensitivity to platinum-containing drugs is believed to be a function of how much
      drug enters the cell, the extent of DNA adduct formation and the rate at which
      DNA is repaired. Activation of protein kinase C by 12-O-tetradecanoyl-phorbol-13
      acetate (TPA) was found to enhance the sensitivity of human ovarian carcinoma
      2008 cells to cisplatin (DDP), carboplatin (CBDCA) and (glycolato-O,O')
      diammineplatinum(II) (254-S). TPA was able to enhance the sensitivity of the DDP
      resistant 2008/C13*5.25 subline to each of the three drugs to the same extent as
      for the 2008 cells. TPA produced no significant change in the uptake of [3H]cis
      dichloro(ethylenediamine)-platinum(II). ([3H]DEP) or CBDCA. It did not alter
      glutathione content or glutathione-S-transferase activity, and induced rather
      than suppressed metallothionein IIA mRNA levels. TPA did increase the formation
      of intrastrand guanine-guanine cross-links by a factor of 1.5 +/- 0.3 (s.d.), and
      reduced the fraction of intrastrand adducts removed from DNA over the subsequent
      24 h by a factor of 1.3 +/- 0.2 (s.d.) (n = 4; P < 0.05), however, these effects
      were too small to account for the degree of TPA-induced sensitisation. These
      results indicate that the mechanism of TPA-induced sensitisation is not specific
      to any one structural form of platinum-containing drug, and that it is not
      readily explicable on the basis of an effect on the four major parameters
      currently believed to regulate DDP sensitivity.

PMID- 8297719
TI  - Molecular genetic investigation of sporadic renal cell carcinoma: analysis of
      allele loss on chromosomes 3p, 5q, 11p, 17 and 22.
AB  - To investigate the role of tumour-suppressor genes on the short arm of chromosome
      3 in the mechanism of tumorigenesis in non-familial renal cell carcinoma, we
      analysed 55 paired blood-tumour DNA samples for allele loss on chromosome 3p and
      in the region of known or putative tumour-suppressor genes on chromosomes 5, 11,
      17 and 22. Sixty-four per cent (35/55) of informative tumours showed loss of
      heterozygosity (LOH) of at least one locus on the short arm of chromosome 3,
      compared with only 13% at the p53 tumour-suppressor gene and 6% at 17q21. LOH at
      chromosome 5q21 and 22q was uncommon (2-3%). Detailed analysis of the regions of
      LOH on chromosome 3p suggested that, in addition to the VHL gene in chromosome
      3p25-p26, mutations in one or more tumour-suppressor genes in chromosome 3p13-p24
      may be involved in the pathogenesis of sporadic renal cell carcinoma (RCC). We
      also confirmed previous suggestions that chromosome 3p allele loss is not a
      feature of papillary RCC (P < 0.05).

PMID- 8297718
TI  - Prevalence of human papillomavirus DNA in cutaneous neoplasms from renal
      allograft recipients supports a possible viral role in tumour promotion.
AB  - It is well established that renal allograft recipients (RARs) have an increased
      incidence of viral warts and premalignant and malignant cutaneous lesions, and
      the risk of their development increases in proportion to duration of graft
      survival. It has been postulated that, in addition to the effects of prolonged
      immunosuppression and previous sun exposure, human papillomaviruses (HPV) may
      also contribute to the carcinogenic process. In this study, the prevalence of HPV
      DNA was examined in a range of premalignant and malignant cutaneous tumours from
      50 immunosuppressed patients (47 renal allograft recipients plus three cardiac
      allograft recipients) and 56 immunocompetent patients using Southern
      hybridisation as a low-stringency screening method and type-specific polymerase
      chain reaction (PCR) assays for eight HPV types. The combined results for renal
      allograft recipients show that HPV DNA was detectable in 79% of viral warts, 42%
      of premalignant keratoses, 33% of intraepidermal carcinomas, 43% of invasive
      squamous cell carcinomas and 16% of uninvolved skin specimens (squamous cell
      carcinomas/renal allograft recipients significantly different at P < 0.05 from
      uninvolved skin specimens/renal allograft recipients). In immunocompetent
      patients the pattern of HPV DNA prevalence was 100% for viral warts; 25% for
      keratoses, 23% for intraepidermal carcinomas, 22% for squamous cell carcinomas
      and 8% for uninvolved skin. No single HPV type predominated in tumour specimens
      from either group. More tumours were found to contain HPV DNA by Southern
      hybridisation analysis than PCR, indicating the presence of HPV types other than
      HPV 1, 2, 5, 6, 8, 11, 16 and 18 in some tumours. However, 'low cancer risk' HPV
      types 1, 2 and 6 as well as 'high cancer risk' HPV types 5 and 16 were
      specifically detected by PCR in a small number of neoplasms. These data suggest
      that multiple HPV types may contribute to cutaneous neoplasia in RARs and that
      they appear to act early in the process of carcinogenesis, perhaps by functioning
      as tumour promoters via stimulation of cell proliferation.

PMID- 8297720
TI  - Response of peritoneal solid tumours after intraperitoneal chemohyperthermia
      treatment with cisplatin or carboplatin.
AB  - The combination of heat and chemotherapy was studied in an intraperitoneal tumour
      model. Rats bearing peritoneal CC531 tumours (2-6 mm) were treated i.p. with cDDP
      or CBDCA [maximal tolerated dose (MTD)] in combination with regional hyperthermia
      (41.5 degrees C, 1 h) of the peritoneal cavity. The addition of hyperthermia to
      the i.p. treatment led to a decrease in the MTD of cDDP by 33.3% at 41.5 degrees
      C. This was due to increased nephrotoxicity. The MTD of CBDCA did not change as a
      result of hyperthermia treatment. The chemo-hyperthermia treatment resulted in
      more cDDP or CBDCA DNA adducts in peritoneal tumours after the combined treatment
      than after chemotherapy alone. The increased tumour platinum concentrations,
      rising from 1.3 micrograms Pt g-1 tumour at 37 degrees C to 5.4 micrograms Pt g-1
      tumour at 41.5 degrees C for cDDP and from 0.2 microgram Pt g-1 tumor to 0.7
      microgram Pt g-1 tumour at 41.5 degrees C for CBDCA, contributed considerably to
      the enhanced numbers of cDDP or CBDCA DNA adducts. As a result of the latter,
      i.p. chemotherapy combined with regional hyperthermia led to an increase in
      tumour growth delay (TGD) after increasing the temperature to 41.5 degrees C for
      cDDP and CBDCA (by 40 days for cDDP, 22 days for CBDCA). These data were in
      agreement with the in vitro findings, i.e. that higher temperatures led to
      increased cytotoxicity.

PMID- 8297721
TI  - Mechanism of differential sensitivity of human bladder cancer cells to mitomycin
      C and its analogue.
AB  - This study was undertaken to elucidate the mechanism(s) of differential
      sensitivity of human bladder cancer cell lines J82 and SCaBER to mitomycin C
      (MMC) and its analogue, BMY 25067. The IC50 values for MMC and BMY 25067 in the
      SCaBER cell line were respectively 5- and 4-fold higher than in J82. BMY 25282
      and BMY 25067 were significantly more cytotoxic, on a molar basis, than MMC in
      both the cell lines. NADPH cytochrome P450 reductase and DT diaphorase activities
      were significantly higher in the J82 cell line than in SCaBER, suggesting that
      relatively lower sensitivity of the SCaBER cell line to MMC and BMY 25067 may be
      due to deficient drug activation. This conclusion was supported by the
      observation that IC50 values for BMY 25282, which has lower quinone reduction
      potential than MMC and BMY 25067, did not differ significantly in these cell
      lines. A correlation between drug sensitivity, oxyradical formation and levels of
      antioxidative enzymes was not observed. These results suggest that the relatively
      lower sensitivity of SCaBER cells to MMC or BMY 25067 may be independent of
      differential oxyradical formation. MMC-induced DNA interstrand cross-link (ISC)
      formation was markedly lower in the SCaBER cell line than in J82. However, it
      remains to be seen if the reduced ISC frequency in the SCaBER cell line is a
      consequence of deficient drug activation or results from increased repair of the
      damaged DNA.

PMID- 8297722
TI  - The selection of antibodies for targeted therapy of small-cell lung cancer (SCLC)
      using a human tumour spheroid model to compare the uptake of cluster 1 and
      cluster w4 antibodies.
AB  - Spheroids of a small-cell lung cancer (SCLC) cell line POC were used to evaluate
      the uptake and penetration of two antibodies recognising different SCLC antigens.
      Spheroids approximately 300-400 microns in diameter were incubated with 1
      microgram ml-1 125I-labelled NY.3D11, an antibody which reacts with the cluster 1
      group antigen (neural cell adhesion molecule; NCAM) and [125I]SWA11, which binds
      to the cluster w4 antigen. The rate of uptake of both antibodies was similar; an
      initially rapid phase was seen during the first 8 h and maximum uptake occurred
      by 24 h. The mean uptake per spheroid at 24 h was 0.97 ng for [125I]NY.3D11 and
      0.45 ng for [125I]SWA11. An objective measurement of antibody penetration into
      spheroids was developed using a computerised image analysis of immunostained
      sections of spheroids. The concentration of antibody and incubation times were
      varied. Both antibodies penetrated the spheroids to a depth of 50 microns after
      30 min. This increased to about 100 microns after 4 h incubation with 1 or 100
      micrograms ml-1 SWA11. The results with 1 microgram ml-1 NY.3D11 were similar,
      but in the presence of 100 micrograms ml-1 NY.3D11 penetration into the spheroid
      was deep and diffuse. These results demonstrate a major concentration-dependent
      difference in the uptake and penetration of cluster 1 and cluster w4 antibodies
      in this spheroid model and they have implications for the selection of antibodies
      for targeted therapy of SCLC.

PMID- 8297723
TI  - Products of vasopressin gene expression in small-cell carcinoma of the lung.
AB  - Small-cell neuroendocrine carcinoma of the lung is known to express products
      related to the vasopressin gene, although these products have been reported to
      sometimes differ from those generated by neurones of the hypothalamo
      neurohypophyseal system. To further investigate vasopressin gene expression in
      neuroendocrine carcinomas, we performed immunohistochemistry on 24 histologically
      classified small-cell carcinomas using antibodies directed against different
      regions of the vasopressin precursor. All of the tumours examined contained at
      least two parts of the vasopressin precursor, suggesting that vasopressin might
      have a biological role in these tumours and indicating a role for these products
      in tumour diagnosis and treatment. Sixty-seven per cent of the tumours contained
      immunoreactivity for all major regions of the precursor: vasopressin, vasopressin
      associated human neurophysin, the bridging region between the hormone and the
      neurophysin, and vasopressin-associated human glycopeptide. However, 33% of the
      tumours examined appeared to express only part of the vasopressin precursor, as
      evidenced by the absence of immunoreactivity for the neurophysin and/or the
      glycopeptide. These results support the proposition that both normal and abnormal
      vasopressin gene expression occurs in small-cell carcinoma of the lung.

PMID- 8297725
TI  - Production of placental alkaline phosphatase (PLAP) and PLAP-like material by
      epithelial germ cell and non-germ cell tumours in vitro.
AB  - Placental and placental-like alkaline phosphatase (PLAP) levels in the culture
      media of 87 cell lines of neoplastic and 'normal' origin were measured by a
      conventional immunosorbent enzymatic assay (IAEA) and by a new immunoradiometric
      assay (IRMA). The IRMA detected immunoreactive PLAP in 37 of 80 (46%) human
      epithelial and germ cell cultures, while the IAEA detected PLAP in only 25 (33%).
      Of the 52 non-germ cell tumour cultures, the IRMA detected expression in 24 (46%)
      and the IAEA in only 16 (31%). In 17 cases (21%) the IRMA recorded levels double
      that of the IAEA, while in five cultures (6%) the reverse was true. The IRMA was
      much more robust than the IAEA and had considerably lower inter- and intra-assay
      coefficients of variation (3.75-8.5% vs 5.2-46%). Detection of PLAP(-like)
      expression by IAEA is dependent on neoplastic expression of enzymatically
      functional molecules and quantification assumes constant enzyme kinetics. PLAP
      like material has a higher catalytic rate constant than PLAP and thus will give
      higher values on a stoichiometric basis in an IAEA. The higher detection rate and
      levels of PLAP-like material in neoplastic cultures when measured by the IRMA
      clearly demonstrate ectopic expression of non-enzymatic PLAP and PLAP-like genes.
      The incidence of PLAP(-like) expression by non-germ cell and possible germ cell
      tumours has been underestimated and its utility as a tumour marker should be re
      examined using assays which measure antigen mass rather than phosphatase
      activity.

PMID- 8297724
TI  - Conserved cis-elements bind a protein complex that regulates Drosophila ras2/rop
      bidirectional expression.
AB  - The Drosophila ras2 promoter region exhibits bidirectional activity, as has been
      demonstrated for the human c-Ha-ras1 and the mouse c-Ki-ras. Here we address a
      unique case of ras regulation, as Drosophila ras2 provides the only example to
      date in which the flanking gene (rop) and its product have been isolated. A
      linking mechanism of control suggests a mutual interaction between the two gene
      products. Our studies indicate that the Drosophila ras2 promoter region shares
      with the human c-Ha-ras1 promoter a CACCC box and an AP-1-like sequence. A 14 bp
      promoter fragment which holds a CACCC element is demonstrated to interact with a
      specific transcription factor (factor B). This CACCC promoter element represents
      a stretch of imperfect palindrome. We present evidence that this factor can form
      a complex with another specific DNA-binding protein (factor A). The binding sites
      (A + B) for these protein factors are essential for 95% expression of both genes
      flanking the promoter (ras2 and rop). Region A consists of four overlapping
      consensus sequences: a TATA-like element, a DSE-like motif (the core sequence of
      the serum response element), a DRE octamer, which has been shown to play a role
      in cell proliferation, and a 5 bp direct repeat representing the GATA consensus
      sequence. Factor A has a very weak affinity to the full promoter region, but when
      complexed with factor B binding efficiency is enhanced. We also show that
      alterations of DNA-protein binding specificities can be achieved by supplementing
      the growth media with different sera.

PMID- 8297726
TI  - Procoagulant activity may be a marker of the malignant phenotype in experimental
      prostate cancer.
AB  - Using a one-stage kinetic chromogenic assay, we studied the procoagulant activity
      (PCA) of prostatic tissue in an experimental model of prostate cancer in the rat.
      PCA was present in homogenates of rat prostate glands containing either benign or
      malignant tumours. The procoagulant activated factor X directly and was
      provisionally characterised as a tissue factor-factor VIIa complex. There was no
      significant differences in PCA between control rats and rats exposed to
      carcinogens that did not develop tumour. Levels in rats that developed tumours
      were significantly higher (P < 0.01) than all other groups and there was a
      positive correlation between tumour weight and PCA (r = 0.85, P < 0.001).
      Furthermore, prostatic PCA levels were higher in the metastasis (P < 0.02). We
      conclude that PCA reflects the malignant phenotype in this animals, the PCA of
      the primary tumour was compared with that of the corresponding secondary deposit
      and levels were higher in the metastasis (P < 0.02). We conclude that PCA
      reflects the malignant phenotype in this model of experimental prostate cancer
      and suggest that this parameter is worth evaluating as a potential tumour marker
      in the human disease.

PMID- 8297727
TI  - L1210 cells selected for resistance to methoxymorpholinyl doxorubicin appear
      specifically resistant to this class of morpholinyl derivatives.
AB  - We investigated the mechanism of resistance in murine L1210 leukaemia cells
      selected after treatment with FCE 23762 methoxymorpholinyl doxorubicin: (MMRDX),
      a methoxymorpholinyl derivative of doxorubicin active in vitro and in vivo on
      multidrug-resistant (mdr) cells, currently undergoing phase I clinical trials.
      The resistant subline obtained after repeated in vitro treatments, L1210/MMRDX,
      is resistant in vitro and in vivo to all tested methoxymorpholinyl derivatives
      and to cyanomorpholinyl doxorubicin, but shows resistance to morpholinyl
      derivatives only in vivo or following their activation with rat S9-liver
      fractions in vitro. L1210/MMRDX cells are sensitive to classic mdr- and altered
      topoisomerase (AT)-mdr-associated drugs. These cells do not appear to overexpress
      the mdr1 gene, nor do they exhibit impaired intracellular drug accumulation and
      efflux or altered levels of glutathione and glutathione S-transferase. The extent
      of DNA single-strand break formation and, after microsomal activation, of DNA
      interstrand cross-links after treatment with MMRDX was similar in the parent and
      the resistant subline. The mechanism of resistance in L1210/MMRDX cells remains
      to be identified but may prove a novel one, highly specific for this class of mdr
      active anthracyclines.

PMID- 8297728
TI  - Increase in mast cells and hyaluronic acid correlates to radiation-induced damage
      and loss of serous acinar cells in salivary glands: the parotid and submandibular
      glands differ in radiation sensitivity.
AB  - The detailed mechanisms which can explain the inherent radiosensitivity of
      salivary glands remain to be elucidated. Although DNA is the most plausible
      critical target for the lethal effects of irradiation, interactions with other
      constituents, such as cell membrane and neuropeptides, have been suggested to
      cause important physiological changes. Moreover, mast cells seem to be closely
      linked to radiation-induced pneumonitis. Therefore, in the present study the
      effects of fractionated irradiation on salivary glands have been assessed with
      special regard to the appearance of mast cells and its correlation with damage to
      gland parenchyma. Sprague-Dawley strain rats were unilaterally irradiated to the
      head and neck with the salivary glands within the radiation field. The
      irradiation was delivered once daily for 5 days to a total dose of 20, 35 and 45
      Gy. The contralateral parotid and submandibular glands served as intra-animal
      controls and parallel analysis of glands was performed 2, 4, 10 or 180 days
      following the last radiation treatment. Morphological analysis revealed no
      obvious changes up to 10 days after the irradiation. At 180 days a radiation dose
      dependent loss of gland parenchyma was seen, especially with regard to serious
      acinar cells in parotid gland and acinar cells and serous CGT (convoluted
      granular tubule) cells in the submandibular gland. These changes displayed a
      close correlation with a concomitant dose-dependent enhanced density of mast
      cells and staining for hyaluronic acid. This cell population seems to conform
      with the features of the connective tissue mast cell type. The parotid seems to
      be more sensitive to irradiation than the submandibular gland. Thus, the present
      results further strengthen the role of and the potential interaction of mast
      cells with radiation-induced tissue injury and alterations in normal tissue
      integrity.

PMID- 8297729
TI  - Cancer morbidity in alcohol abusers.
AB  - Data on the association between alcohol abuse and cancer morbidity are scarce in
      large cohorts of non-hospitalised alcoholic men and women. Of 18,368 alcohol
      abusers who entered an outpatient clinic in Copenhagen during 1954-87, 18,307
      were followed and their cancer incidence was compared with that of the total
      Danish population. On average the 15,214 men were observed for 12.9 years and the
      3,093 women for 9.4 years. The overall morbidity of cancer was increased
      significantly. Of the men, 1,441 developed cancer [relative risk (RR) = 1.6; 95%
      confidence interval (CI) = 1.5-1.7], while 182 women did (RR = 1.5; 95% CI 1.3
      1.8). Significantly increased incidences were found of cancer in the tongue,
      mouth, pharynx, oesophagus, liver, larynx, lung and pleura and secondary cancer.
      The women had significantly increased risk of cervical cancer (RR = 2.0; 95% CI
      1.2-3.0). The men developed prostatic cancer significantly more frequently than
      expected (RR = 1.4; 95% CI 1.2-1.8). The risk of melanomas (RR = 0.5; 95% CI 0.2
      0.8) was significantly lower than expected. The relative risks of cancer of the
      stomach, pancreas, kidney and endocrine system were only slightly increased. The
      study group did not develop more colonic (RR = 1.0; 95% CI 0.8-1.3) or rectal
      cancer (RR = 1.0; CI 0.7-1.3) than expected. The risk of breast cancer in women
      was slightly increased (RR = 1.3; 95% CI 0.9-1.7), but not statistically
      significant. Thus, the associations between alcohol and cancer of the upper
      digestive and respiratory tract and the liver are confirmed. In addition, this
      study indicates an increased occurrence of cancer of the prostate gland, pleura
      and uterine cervix in alcohol abusers.

PMID- 8297730
TI  - Kaposi's sarcoma in Italy before and after the AIDS epidemic.
AB  - The incidence of Kaposi's sarcoma (KS) in 1976-90 was assessed in Italy, taking
      advantage of a network of nine population-based cancer registries covering, at
      its maximum, approximately 5.6 million subjects. The first examined period (1976
      84) substantially reflects the epidemiology of KS prior to the AIDS epidemic in
      the registration areas. Elevated incidence rates, standardised to the Italian
      population of 1981, of 1.05/100,000 men and 0.27/100,000 women emerged in 1976-84
      (i.e. from two- to threefold higher than in the USA and Sweden, more than tenfold
      higher than in England and Wales). These high rates, especially remarkable in the
      Registry from the south of Italy (i.e. Ragusa, 3.01/100,000 men and 0.54/100,000
      women) suggest that the prevalence of the still unknown causative agent for KS
      was high, at least in some parts of Italy, prior to the AIDS epidemic. In the
      most recent period (1985-90), an approximately twofold increase in KS incidence
      rates in Italian men below age 50 was observed (from 0.15 in 1976-84 to 0.47 in
      1985-90). Conversely, declines in KS incidence were recorded in older men.

PMID- 8297731
TI  - p53 and bcl-2 expression in high-grade B-cell lymphomas: correlation with
      survival time.
AB  - B-cell high-grade lymphomas are heterogeneous in terms of histology, clinical
      presentation, treatment response and prognosis. As bcl-2 and p53 gene
      deregulations are frequently involved in several types of lymphoid malignancies,
      we aimed our investigation at the study of the relation between bcl-2 and p53
      expression and survival probability in a group of 119 patients with B-cell high
      grade lymphoma. These were obtained from the Virgen de la Salud Hospital, Toledo,
      Spain (73 cases), John Radcliffe Hospital, Oxford, UK (31 cases), and the
      Istituto Nazionale dei Tumori, Milan, Italy (15 cases). The relation between bcl
      2 protein expression and survival was small, depending on the primary
      localisation of the tumour (in lymph node of mucosae), and lacked a significant
      correlation with overall survival. In contrast with this, p53 expression was
      related to survival probability in our series, this relation being both
      significant and independent of histological diagnosis. p53-positive patients
      showed a sudden decrease in life expectancy in the first months after diagnosis.
      Multivariant regression analysis confirmed that the only parameters significantly
      related with survival were extranodal origin, which is associated with a better
      prognosis, and p53 expression, which indicates a poor prognosis. Simultaneous
      expression of bcl-2 and p53 was associated with a poorer prognosis than p53
      alone. This is particularly significant for large B-cell lymphomas presenting in
      lymph nodes. The cumulative poor effect of both p53 and bcl-2 in large B-cell
      lymphomas, which is more significant in nodal tumours, could confirm the
      existence of a multistep genetic deregulation in non-Hodgkin's lymphoma. This
      indicates that the genetic mechanisms controlling apoptosis and their
      disregulation are critical steps in the progression of lymphomas.

PMID- 8297732
TI  - Circulating levels of colony-stimulating factor 1 as a prognostic indicator in 82
      patients with epithelial ovarian cancer.
AB  - Serum samples from 82 patients with epithelial ovarian cancer, previously assayed
      for CA125, were assayed for circulating colony-stimulating factor 1 (CSF-1). An
      elevated CSF-1 concentration (> 450 U ml-1 or > 5.42 ng ml-1) was significantly
      associated with a worse survival (P = 0.02). The predictive value of raised CSF-1
      levels was retained whether the first available sample for all patients (n = 82)
      or the first sample at the start of chemotherapy (n = 41) was considered. Mean
      CSF-1 levels (n = 14) dropped significantly during six courses of platinum-based
      chemotherapy (P = 0.02). Although an elevated CA125 concentration appeared to be
      a prognostic indicator in the total population (n = 82), it was not related to
      prognosis in the group of patients from whom samples had been drawn at the start
      of chemotherapy. In a Cox proportional hazards model, CSF-1, but not CA125, was
      significantly associated with outcome following adjustment for stage, grade and
      degree of surgical clearance.

PMID- 8297733
TI  - Peripheral blood involvement in non-Hodgkin's lymphoma detected by clonal gene
      rearrangement as a biological prognostic marker.
AB  - Peripheral blood from 67 patients with non-Hodgkin's lymphoma was examined at
      initial diagnosis for the presence of circulating lymphoma cells by DNA
      hybridisation using immunoglobulin and T-cell receptor gene probes. Clonal gene
      rearrangement was found in 31% (21/67) of patients and correlated with clinical
      stage, histological grade and bone marrow involvement. Clinical stage and the
      presence of lymphoma cells in peripheral blood were prognostic factors for
      progression-free survival in all patients on univariate analysis, but the
      detection of lymphoma cells was not independent of stage. It was also not a
      significant predictor for survival. In patients with intermediate- and high-grade
      lymphoma, the detection of lymphoma cells in peripheral blood was a significant
      prognostic factor for progression-free survival (PFS) and survival only on
      univariate analysis. The 3-year PFS was 17% in patients with circulating lymphoma
      cells compared with 75% if these were absent (P < 0.05). The presence of lymphoma
      cells in peripheral blood is associated with extensive disease and may be a
      biological marker of poor disease control. Sensitive techniques of detection
      should form part of large prospective studies in non-Hodgkin's lymphoma.

PMID- 8297734
TI  - A prospective study on obesity and subcutaneous fat patterning in relation to
      breast cancer in post-menopausal women participating in the DOM project.
AB  - The associations of body fat and body fat distribution with breast cancer risk
      were examined in a prospective study in 9,746 post-menopausal women with a
      natural menopause, aged 49-66 at intake, participating in a breast cancer
      screening project (the DOM project in Utrecht). During a follow-up period of 15
      years (mean follow-up time 12.5 years) 260 women developed breast cancer. Fat
      distribution, assessed by contrasting groups of subcapsular and triceps skinfold
      thickness, was found to be unrelated to breast cancer incidence. No significant
      relationship between body fat, measured either by weight, Quetelet's index,
      triceps skinfold or subscapular skinfold, and breast cancer risk was found when
      analysed in quartiles. However, women in the upper decile compared with the lower
      decile of the distribution of Quetelet's index were found to have a 1.9 times
      (95% CI 1.1-3.3) higher risk for breast cancer. These results seemed to be in
      contrast with the significant positive association between fatness, analysed in
      quartiles, and breast cancer observed in a cross-sectional study, based on
      mammographic screening, carried out previously in the same population. Although
      the differences between the present, prospective, study and our cross-sectional
      study may be due to chance it may be that there are differences between
      characteristics of breast cancer detected at screening and subsequently, which
      influence the associations between measures of fatness and risk of breast cancer.

PMID- 8297735
TI  - Relationship between Quetelet's index and cancer of breast and female genital
      tract in 47,000 women followed for 25 years.
AB  - The relationship between Quetelet's index and subsequent risk for cancer of
      endocrine target organs was studied in a cohort of 47,003 women, examined for
      height and weight in the years 1963-65, and followed up in the Swedish Cancer
      Register until 1987. High Quetelet's index was associated with a decreased risk
      for breast cancer among women less than 55 years of age at risk, while a high
      Quetelet's index predicted an increased risk among older women. Among women > or
      = 55 years of age, the excess relative risk for breast cancer associated with
      high Quetelet's index declined significantly during the follow-up period. Cancer
      of the ovaries and the uterine cervix were not significantly related to
      Quetelet's index in any age group. In women > or = 55 years of age, the relative
      risk for cancer of the uterine corpus associated to Quetelet's index was higher
      than that for breast cancer, and this association persisted during the entire
      follow-up period of more than 20 years. In spite of the fact that endometrial
      cancer is less common than breast cancer, because of the stronger relation
      between overweight and endometrial cancer, more endometrial cancer would be
      attributable to obesity than breast cancer.

PMID- 8297736
TI  - A comparative study on hepatocellular carcinoma between South Africans and
      Japanese from the viewpoint of nuclear DNA content.
AB  - Nuclear deoxyribonucleic acid (DNA) content of hepatocellular carcinoma (HCC) in
      41 South African and 47 Japanese patients at autopsy was analysed by dual
      wavelength microspectrophotometry. The DNA distribution patterns were classified
      as type I, II, III or IV and as low ploidy (types I, II) or high ploidy (types
      III, IV), according to the degree of dispersion. We found a significantly higher
      incidence of high ploidy in South African HCC than in Japanese HCC. Moreover,
      type IV was significantly more frequent among South Africans than among the
      Japanese. These findings demonstrate that large differences in biological
      characteristics and clinical behaviour of HCC between South Africa and Japan may
      reflect differences in DNA distribution patterns which we observed between these
      two races.

PMID- 8297737
TI  - K-ras mutation in colorectal cancer: relations to patient age, sex and tumour
      location.
AB  - DNA from 251 primary tumours obtained from 123 male and 125 female Norwegian
      patients with colorectal carcinoma was analysed for the presence of K-ras point
      mutations at codons 12 and 13. Mutations were found in 99 (39%) of the samples.
      The frequency of K-ras mutations was significantly related to age and sex of the
      patients, and to the location of the tumours (overall: P = 0.008). K-ras
      mutations were much less frequent in colonic tumours from male than female
      patients at younger ages (< 40 years, odds ratio < 0.014). The low frequency
      might indicate that a different, ras-independent, pathway to neoplasia is
      dominating in the colon of younger males. In contrast, older men had more
      mutations than older women (e.g. 90 years, odds ratio = 5.8). An inverse but less
      pronounced relationship was seen for rectal tumours. The type of mutation was
      found to be associated to sex of patient and location of tumour. G-->C
      transversions accounted for 35% of the mutations in rectal tumours from females,
      in contrast to only 2.5% in the rest of the material (P = 0.0005). This may
      indicate that there are specific carcinogens acting in this location.

PMID- 8297738
TI  - Hepatic arterial chemotherapy for metastatic colorectal carcinoma.
AB  - In this review, the rationale of regional chemotherapy for treatment of hepatic
      metastases in advanced colorectal carcinoma is discussed. Pharmacokinetic
      principles and early clinical experience of hepatic arterial drug administration
      are summarised. The regional advantage of fluoropyrimidine compounds in this
      setting is well established, and recent evidence suggests that 5-fluorouracil (5
      FU) is more efficacious than the analogue 5-fluoro-2'-deoxyuridine (FUDR).
      However, while significantly higher clinical response rates can be achieved with
      hepatic arterial infusion (HAI) chemotherapy compared with conventional
      intravenous drug administration, patient survival benefit is not significantly
      different. Several novel approaches to overcome the limitations of HAI therapy
      are currently being explored. These include concomitant use of biodegradable
      microspheres, which both slow tumour blood flow and enhance tumour drug uptake,
      and use of vasoactive agents to redistribute arterial blood flow towards tumours.
      In addition, novel chemotherapeutic agents which exploit unique biological
      characteristics of hepatic tumours are entering clinical trial.

PMID- 8297739
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) allows acceleration and
      dose intensity increase of CEF chemotherapy: a randomised study in patients with
      advanced breast cancer.
AB  - A randomised study was conducted in 62 patients with advanced breast cancer to
      assess whether granulocyte-macrophage colony-stimulating factor (GM-CSF) would
      yield an increase in the dose intensity of a standard-dose CEF regimen through an
      acceleration of chemotherapy administration. Patients received CEF
      (cyclophosphamide 600 mg m-2, epidoxorubicin 60 mg m-2 and fluorouracil 600 mg m
      2) i.v. on day 1 or the same chemotherapy, plus GM-CSF 10 micrograms kg-1 s.c.
      starting from day 4, repeated as soon as haematopoietic recovery from nadir
      occurred. Patients in the CEF + GM-CSF group received chemotherapy at a median
      interval of 16 days compared with 20 days in the control group. This led to a
      significant increase (P = 0.02) in the dose intensity actually administered in
      the third, fourth and sixth cycles: +28%, +25%, +20% respectively. Non
      haematological toxicity was mild. GM-CSF had to be reduced or suspended in 50% of
      patients because of toxicity. Haematological toxicity, mainly cumulative anaemia
      and thrombocytopenia, was manageable. An increase in response rate for patients
      with measurable disease, of borderline statistical significance (P = 0.088, P for
      trend = 0.018), from 42% in the CEF group to 69% in the CEF + GM-CSF group, was
      observed. This randomised trial indicates that GM-CSF is useful for chemotherapy
      acceleration. Accelerated CEF + GM-CSF is a moderately dose-intensive regimen
      that can be administered in an outpatient clinic and is associated with a high
      objective response.

PMID- 8297740
TI  - Cisplatin, 5-fluorouracil and interferon alpha 2b for recurrent or metastatic
      head and neck cancer.
AB  - On the basis of preclinical data suggesting the possibility of maximising the
      efficacy of 5-fluorouracil and cisplatin by interferon, a pilot clinical trial
      was initiated in recurrent and/or metastatic head and neck cancer. Thirty-four
      patients were treated with cisplatin at 100 mg m-2, followed by 5-fluorouracil at
      1,000 mg m-2 by continuous infusion for 5 days. Interferon alpha 2b was
      administered at the dose of 3 million U i.m. daily for 7 days, beginning the day
      before chemotherapy. Courses were repeated every 3 weeks. Two patients achieved a
      complete remission, six a partial response, 14 had stable disease and 12
      progressed on therapy, for an overall response rate of 23% (95% confidence
      interval 10-36%). Median survival time was 5 months. Toxicity was severe.
      Stomatitis, diarrhoea and myelosuppression were the most common side-effects.
      Because of the poor response rate and the presence of severe toxicity, in our
      opinion further clinical trials in head and neck cancer should be attempted only
      after a better definition in preclinical studies of interactions among 5
      fluorouracil, cisplatin and interferon.

PMID- 8297741
TI  - pS2 and response to adjuvant hormone therapy in primary breast cancer.
AB  - We reviewed 319 primary breast tumours for cytosolic pS2 content, with a median
      follow-up of 6 years. pS2 status correlated positively with oestradiol and
      progesterone receptors and negatively with Scarff, Bloom and Richardson grade.
      pS2 positivity was associated with longer overall survival, particularly in
      patients who received hormone therapy, in whom pS2 status was also predictive of
      the response to therapy.

PMID- 8297743
TI  - 1st international Beatson symposium--cellular, molecular and clinical aspects of
      squamous cell carcinomas.
AB  - About 80% of neoplasias are epithelial in origin and, as such, understanding the
      molecular mechanisms involved in the development of epithelial tumours is vital
      to the diagnosis, prognosis and treatment of the vast majority of human cancers.
      Obviously this is no easy task but, as outlined above, great efforts are being
      made to identify important molecules involved in the progression of normal
      epithelial cells to carcinoma. The development of techniques to identify new
      oncogenes is of particular importance, and hopefully the cDNA expression cloning
      system of Stuart Aaronson will be a useful tool in this respect. The potential of
      some of these molecules to be used as therapeutic targets will require the
      development of suitable screening procedures, such as that being established by
      Chris Marshall for the ras-Map kinase pathway in yeast. It is encouraging that
      the immune response to virally (HPV) induced cancer is being carefully elucidated
      and the prospects of vaccine development for the treatment of cervical cancer
      coming nearer since this particular form of SCC is a major cancer globally.
      Finally it was fitting to end the meeting on an optimistic note with John
      Mendelsohn's EGFR monoclonal antibody therapy entering clinical trials, and
      hopefully this will prove efficacious in the treatment of human SSC.

PMID- 8297742
TI  - Prognostic value of urokinase-type plasminogen activator (uPA) and plasminogen
      activator inhibitors PAI-1 and PAI-2 in breast carcinomas.
AB  - It is now clearly established that proteolytic enzymes, including plasminogen
      activator (uPA), play an important role in breaking down the extracellular
      matrix, which is considered to be a step in metastasis formation. Plasminogen
      activators are controlled at various levels. Two inhibitors, PAI-1 and PAI-2,
      have been identified, the latter being more specific for uPA. In attempts to
      determine their prognostic value, it is essential to investigate the relative
      importance of these parameters and their interactions. We used an immunoenzymatic
      method to assay uPA, PAI-1 and PAI-2 antigens in cytosols prepared from 314
      primary breast tumours. The patients were followed up for a minimum of 6 years
      and all relevant clinical and laboratory findings were recorded. Univariate
      analysis confirmed the poor outcome of patients whose tumours contained large
      amounts of uPA and PAI-1. In addition, low levels of PAI-2 correlated with
      shorter disease-free survival in the overall population (P = 0.02), post
      menopausal women (P = 0.02) and women without lymph node involvement (P = 0.02).
      Multivariate analysis in the 'main effects' Cox model identified node
      involvement, macroscopic tumour size and PAI-2 as significant variables. The
      'interactive' model, taking into account interactions between uPA and its two
      inhibitors, identified a first subgroup with a very poor prognosis associating
      either high levels of PAI-1 with low levels of PAI-2 in the overall population
      and the women with no node involvement or high levels of uPA with low levels of
      PAI-2 in the group of menopausal women. We conclude that PAI-1 provides the same
      prognostic information as uPA, and does not appear to play a role as an
      inhibitor. In contrast, PAI-2 increases the prognostic value of uPA, particularly
      in post-menopausal women, and PAI-1 in patients with no node involvement.

PMID- 8297744
TI  - Mental health: listening to voices.

PMID- 8297745
TI  - A healthy start in life.

PMID- 8297746
TI  - Northern Ireland: trouble in store.

PMID- 8297747
TI  - Representational systems in counselling.
AB  - The theories of neuro-linguistic programming are becoming more popular in shaping
      the approaches of nurses to counselling. The use of one facet of these theories,
      primary representational systems, is explored here. Examining the case of an
      imaginary patient, the author shows how the primary representational systems of
      patients and health workers can create problems if in disharmony, and how a
      proper understanding can lead to increased empathy and more constructive
      dialogue.

PMID- 8297748
TI  - Performance pay: reviewing the options.

PMID- 8297749
TI  - A study of UK nurses' health behaviours.
AB  - A survey was carried out to give a snap-shot of the health related behaviours of
      a sample of British nurses undertaking part-time study at two educational
      establishments. The behaviours of the sample are related to those found in
      previous US-based studies, and for gender differences. The survey has provided
      the basis for a larger study which is in the planning stage.

PMID- 8297750
TI  - Depression: advances in drug treatment.

PMID- 8297751
TI  - Nurses' knowledge of nebulised therapy.
AB  - Nebulisers are commonly used in the management of chronic obstructive airways
      disease. A survey was therefore conducted to ascertain what nurses knew about
      this form of therapy. Several areas of deficient knowledge were revealed,
      including how to clean the equipment properly, what the flow rate of gas should
      be and what type of gas to use. A standardised protocol for nebuliser therapy is
      included.

PMID- 8297752
TI  - Health hacks borch facts shock!

PMID- 8297753
TI  - Passer-by operations.

PMID- 8297754
TI  - Working parents: losing the battle of all NHS mothers.

PMID- 8297755
TI  - Education: Ann's last lesson.

PMID- 8297756
TI  - Computer reviews. Put staff in their place.

PMID- 8297757
TI  - Diabetes care: dispelling the myths (continuing education credit).

PMID- 8297758
TI  - World news. International. Nurses have been awarded scholarships to pursue their
      education.

PMID- 8297759
TI  - World news. Thailand. The first large-scale trial of an AIDS vaccine.

PMID- 8297761
TI  - Learning disabilities: into Yugoslavia.

PMID- 8297760
TI  - HIV/AIDS: Sunday morning on the Chain gang.

PMID- 8297763
TI  - Welfare in a state.

PMID- 8297764
TI  - Patient-controlled analgesia (continuing education credit).

PMID- 8297762
TI  - Practice development units: the next step?
AB  - Nursing has developed considerably in recent years in a multidisciplinary
      context, acknowledged in the setting up of nursing and practice development
      units. The aim of this article is to demonstrate to readers how the effective
      implementation of decentralised management theory and clinical leadership can
      facilitate practice development and how interdisciplinary collaboration is an
      integral feature of this.

PMID- 8297765
TI  - The contradictions of mental health nursing.
AB  - A widely-held belief among mental health workers is that they provide a patient
      centred, non-institutionalised service to their clients. In this article, the
      author points out the contradictions between this belief and the reality of the
      care. He argues that the blame lies with nursing's inability to formulate its own
      model of care.

PMID- 8297766
TI  - Girly stuff.

PMID- 8297767
TI  - Ethics: ova the hill?

PMID- 8297768
TI  - Do clothes maketh the nurse?

PMID- 8297769
TI  - What did you do in the NHS reforms, Pops?

PMID- 8297770
TI  - One minute wisdom. Professionals should stop using the word 'basic' to describe
      and denigrate nursing skills.

PMID- 8297771
TI  - Sister Susie. Sister Suzuki derides again.

PMID- 8297772
TI  - World AIDS Day. Cash to continue, but more demanded.

PMID- 8297773
TI  - [Practice of inhalation therapy in children].

PMID- 8297775
TI  - [Poisonous and less poisonous plants].

PMID- 8297774
TI  - [Fiber optical bronchoscopy--nursing aspects].

PMID- 8297776
TI  - [Care of children with respiratory diseases in a specialty department for
      pulmonology].

PMID- 8297777
TI  - [Care planning].

PMID- 8297778
TI  - [Use of unskilled workers in pediatrics. Notes to the article "Use of student
      workers in pediatrics" by Marlies Bergers in Kinderkrankenschwester 10/1993, p.
      354].

PMID- 8297779
TI  - [The parents' work in the hospital for disabled children. I. Concept of parents'
      work].

PMID- 8297780
TI  - [Hepatitis B--the most important chronic human viral infection].

PMID- 8297781
TI  - [Thou shalt not feel--thoughts on the psychodynamic action of child abuse].

PMID- 8297782
TI  - [Legal problems within the framework of intensive care medicine].

PMID- 8297783
TI  - [Benefits for rehabilitation--also for beginners].

PMID- 8297784
TI  - [Erich Puschel (1904-1991)].

PMID- 8297785
TI  - A Minute encoding a ribosomal protein enhances wing morphogenesis mutants.
AB  - E(Dl)KP135 has been isolated previously as a recessive lethal Drosophila P
      element insertion line with a dominant enhancing effect on the phenotype of
      Delta, a gene encoding a surface membrane protein. We show here that this P
      insertion also enhances the wing phenotype of nd1, an allele of Notch encoding
      another transmembrane protein, the putative receptor of Delta, as well as that of
      if3, an allele of the integrin gene PS2 alpha. Moreover, we noticed that this P
      insertion causes a severe Minute phenotype. Molecular characterisation revealed
      that the P element disrupts the putative mRNA leader sequence of the ribosomal
      protein L19 gene. We tested further Minute genes and found that two of them,
      similarly to E(Dl)KP135, strongly enhance the nd1 wing phenotype. Our results
      suggest that the pleiotropic Minute syndrome can affect, probably indirectly, one
      or more steps of wing morphogenesis that involve surface adhesion of epithelial
      cells.

PMID- 8297786
TI  - Suramin prevents transcription of dorsal marker genes in Xenopus laevis embryos,
      isolated dorsal blastopore lips and activin A induced animal caps.
AB  - Suramin, a polyanionic compound which is known to interact with the receptors of
      growth factors inhibits the expression of dorsal marker genes in whole embryos
      and isolated dorsal blastopore lips. Suramin also prevents activin A induced
      dorsalization of animal cap explants from blastula stage embryos, but it
      simultaneously evokes a shift of the differentiation pattern from dorsal
      mesodermal structures (notochord, somites) to ventral mesodermal derivatives
      (mesothelium and erythroid precursor cells). The results are consistent with the
      assumption that the dorsal vegetal zone (Nieuwkoop center) primarily releases
      more general/ventral mesodermalization signals. They further suggest a dual role
      of activin A in early embryogenesis. While the maternal component may contribute
      to a more general/ventral type of induction, increasing concentrations of the
      zygotic component along with the activation of primary response genes may
      contribute to the dorsalization of the organizer.

PMID- 8297787
TI  - Brain synapses contain inducible forms of the transcription factor NF-kappa B.
AB  - We investigated the rat brain for the presence and activation state of the
      inducible transcription factor NF-kappa B. Two forms of NF-kappa B containing the
      transactivating p65 subunit were found in all brain regions investigated. The
      majority of NF-kappa B was in an inducible cytoplasmic form by virtue of its
      association with the inhibitory subunit I kappa B. Significant amounts of
      inducible NF-kappa B forms were present in synaptosomes, as suggested by
      electrophoretic mobility shift assay and Western blot analysis of subcellular
      brain fractions. A synaptic localization of NF-kappa B was further evident from
      immunostaining of inner and outer plexiform layers of the retina with an antibody
      directed against the p50 subunit of NF-kappa B. In cerebral cortex and striatum,
      NF-kappa B-specific antibodies showed a punctate immunostaining partially
      overlapping with that for the synaptic marker protein synaptophysin. NF-kappa B
      is thus the first transcription factor found in synapses of neurons. With its
      unusual subneuronal localization, the inducible transcription factor has the
      potential to function as retrograde messenger mediating stimulus-response
      coupling and long-term changes in gene expression following presynaptic
      stimulation.

PMID- 8297788
TI  - A novel cDNA corresponding to transcripts expressed in retina post-mitotic
      neurons.
AB  - The long term objective of this study is to isolate genes specifically expressed
      at the onset of neuronal cell cycle withdrawal. As an experimental paradigm we
      have used a quail neuroretinal cell clone (clone K2) immortalized by a
      thermosensitive mutant of Rous Sarcoma Virus. K2 cells proliferate at 36 degrees
      C but stop synthesizing DNA after a shift to 41.5 degrees C. We have constructed
      a cDNA library from K2 cells transferred to 41.5 degrees C and autosubtracted
      with RNAs from K2 cells maintained at 36 degrees C. This strategy has led to the
      isolation of cDNAs which recognize mRNAs expressed in quail neuroretina (NR)
      during development. We report here one of these cDNAs, cDNA QN1, that hybridizes
      with transcripts expressed in retina neurons, in parallel with their withdrawal
      from the cell cycle. QN1 ORF codes for a 138 kDa polypeptide corresponding to the
      protein observed in Western blot analysis. A role of QN1 product(s) on neuronal
      quiescence is suggested by the positive effect of an antisense oligonucleotide on
      DNA synthesis of K2 cells.

PMID- 8297789
TI  - Wnt-5a and Wnt-7a are expressed in the developing chick limb bud in a manner
      suggesting roles in pattern formation along the proximodistal and dorsoventral
      axes.
AB  - The Wnt gene family encodes a group of secreted signalling molecules that have
      been implicated in the regulation of cell fate and pattern formation during
      embryogenesis. We have examined the patterns of expression of two members of the
      chicken Wnt family, Wnt-5a and Wnt-7a, during development of the chick limb bud.
      Wnt-5a is expressed in the apical ectodermal ridge which directs outgrowth of
      limb mesoderm. Wnt-5a also exhibits three quantitatively distinct domains of
      expression along the proximodistal (PD) axis of the limb mesoderm that may
      correspond to the regions which will give rise to the three distinct PD segments
      of the limb, the autopod, zeugopod, and stylopod. In contrast, Wnt-7a expression
      in the limb bud is specifically limited to the dorsal ectoderm. These
      observations suggest possible roles for Wnt-5a and Wnt-7a in pattern formation
      along the PD and dorsoventral axes of the developing chick limb bud. In addition,
      Wnt-5a and Wnt-7a exhibit spatially discrete domains of expression in several
      other regions of the chick embryo consistent with developmental roles for these
      genes in a variety of other tissues.

PMID- 8297790
TI  - Ectopic expression of genes during chicken limb pattern formation using
      replication defective retroviral vectors.
AB  - A gene transfer method to ectopically express genes during chicken limb pattern
      formation using replication defective retroviral vectors has been established.
      Spherical non-proliferating (mitomycin C treated) aggregates of clonal retrovirus
      producing cells were grafted directly into developing chicken wing buds. The cell
      aggregates had to be placed in direct contact with the highly proliferative cells
      of the wing bud to promote efficient in vivo infection of embryonic cells by the
      released retroviral particles. The majority of grafts resulted in widespread
      expression of a reporter gene (encoding bacterial beta-galactosidase) during limb
      pattern formation and early limb bud outgrowth without affecting morphogenesis.
      This method provides a novel approach to study the effects of ectopic gene
      expression on limb pattern formation. Possible future applications to study other
      developmental processes are discussed.

PMID- 8297791
TI  - A zebrafish homologue of the Drosophila neurogenic gene Notch and its pattern of
      transcription during early embryogenesis.
AB  - We describe here the primary structure of a zebrafish homologue of the Drosophila
      neurogenic gene Notch and its pattern of mRNA accumulation during embryogenesis.
      The gene produces a 8.5 kb transcript encoding a putative transmembrane protein
      with a high degree of sequence similarity to members of the Notch family,
      comprising 36 EGF-like repeats, three lin-12/Notch repeats, six cdc10/SWI6
      repeats, OPA repeats and a PEST sequence. Transcription of the zebrafish Notch
      gene is spatially and temporally regulated. A high density of transcripts, most
      probably of maternal origin, can already be detected in the 2-cell stage. During
      pregastrulation stages, RNA is present in all cells. However, following
      gastrulation, transcripts accumulate in specific regions of the embryo following
      a rapidly changing pattern. In some of these regions, cell divisions take place
      at the time of Notch expression, in others processes of cell differentiation.
      This holds true for various mesodermal derivatives, such as the prospective
      notochord, and for different neural primordia, such as the neural plate and the
      brain vesicles. This pattern of transcript accumulation suggests a role for the
      zebrafish Notch homologue in processes of regionalization and cell
      diversification.

PMID- 8297792
TI  - Robustness of some estimators for the analysis of covariance structures.
AB  - A sampling experiment was designed to evaluate the robustness of some estimators
      used in the analysis of covariance structures to misspecification of the
      discrepancy function in finite samples. The estimators were studied under four
      distribution (a multivariate normal, an elliptical, a non-elliptically symmetric,
      and an asymmetric multivariate distribution, and eight sample size (75, 150, 300,
      600, 1200, 2400, 4800, 9600) conditions. Parameters of the composite direct
      product model for a 6-variable MTMM matrix were estimated using the Maximum
      Wishart Likelihood (MWL), generalized least squares (GLS), asymptotically
      distribution free (ADF), and approximate ADF (DADF) estimators. Browne's
      elliptical correction (CMWL) to the test statistic and standard errors for scale
      invariant models was also made for each sample. Each of the 32 distribution
      sample size conditions was replicated 300 times. The accuracy of the parameter
      estimates and estimated standard errors and the distribution of the test
      statistic were studied. The theoretically predicted importance of information
      contained in higher-order moments of arbitrary distributions was confirmed.
      Robustness of the MWL and normal theory GLS estimators cannot be taken for
      granted. Elliptical corrections may be a practical solution to some data analytic
      problems.

PMID- 8297793
TI  - c-Myc induces the expression and activity of ornithine decarboxylase.
AB  - The role of the product of the c-myc protooncogene in the regulation of cellular
      proliferation and differentiation is well established. Recent reports that c-Myc
      can serve as a sequence-specific transcriptional activator have begun to
      elucidate the mechanism by which c-Myc exerts such a profound effect on the
      mitotic status of a cell. To identify a potential target gene for Myc-mediated
      trans-activation, we examined the regulation of the ornithine decarboxylase (ODC)
      gene by c-Myc. ODC is the first and rate-limiting enzyme involved in the
      synthesis of the polyamines and has been shown to be required for entry into and
      progression through the cell cycle. Using a conditionally active c-Myc-estrogen
      receptor chimeric protein, we found estrogen-dependent activation of ODC
      expression and enzymatic activity. The induction of ODC mRNA expression was not
      dependent upon de novo protein synthesis. These data suggest that one downstream
      pathway for Myc-directed cell cycle control is the induction of ODC expression.

PMID- 8297794
TI  - Two new Drosophila genes related to human hematopoietic and neurogenic
      transcription factors.
AB  - We have identified two new basic domain helix-loop-helix (bHLH) genes in
      Drosophila melanogaster, DroSCL and DroNHLH. DroSCL was identified because of its
      homology to the mammalian hematopoietic transcription factor SCL. DroNHLH was
      similarly identified by homology to NHLH1 and NHLH2, two bHLH genes expressed in
      the developing mammalian nervous system. A partial DroSCL complementary DNA clone
      was obtained from an early pupal (5.5-7.5-day) Drosophila library. DroSCL is 73%
      identical to SCL within the 55-amino acid region of the bHLH domain. A DroNHLH
      complementary DNA clone was obtained from an early instar (I and II) Drosophila
      library. Its coding region consists of 162 amino acids and encodes a predicted
      protein of 18,312 daltons. DroNHLH is 87% identical to NHLH1 and NHLH2 within the
      bHLH domain. DroSCL and DroNHLH are located on the X chromosome. A 1.7-kilobase
      DroSCL transcript and a 1.5-kilobase DroNHLH transcript were detected by Northern
      analysis of total Drosophila RNA. Examination of Drosophila embryos by tissue in
      situ hybridization reveals restricted expression of both genes in a subset of
      cells in the developing central nervous system.

PMID- 8297795
TI  - H-2/myc, E mu/myc, and c-myc transgenic mice: potent sources of early
      hematopoietic cell lines.
AB  - Activation of the cellular c-myc oncogene appears to be linked to the development
      of malignancies in a variety of tissues, in particular, hematopoietic tumors. In
      an attempt to obtain cell lines corresponding to early stages of lymphoid
      differentiation, we have derived several strains of transgenic mice in which
      human c-myc genomic sequences were coupled to various regulatory sequences, H-2,
      E mu, and c-myc. The class I H-2Kb 5' region is active in most adult tissues; the
      activity of the enhancer E mu of the heavy chain immunoglobulin is restricted to
      lymphocytes; and the 2-kilobase-long c-myc 5' region has been shown by in vitro
      experiments to contain most of the sequences required for c-myc regulated
      expression. Regardless of the construct, H-2/myc, E mu/myc, or c-myc, the
      transgenes were mainly expressed in lymphoid tissues. However, the quantity of
      transgene mRNA differed markedly among the transgenic strains, thus providing a
      situation in which the level of c-myc expression could be correlated with tumor
      development. Several cell lines were derived and maintained by in vivo
      transplantation and/or in vitro cultures. All except two of the lines correspond
      to immature T- or B-lymphoblasts, as revealed both by fluorescence-activated cell
      sorting and Southern blot analysis; one cell line corresponds to a gamma delta T
      cell population, and the other to a bipotential mixed lymphoid and myeloid tumor.

PMID- 8297796
TI  - Identification of a thyroid hormone response element in the mouse myogenin gene:
      characterization of the thyroid hormone and retinoid X receptor heterodimeric
      binding site.
AB  - Thyroid hormones are positive regulators of muscle development in vivo. Triiodo-L
      thyronine (T3) treatment of myogenic cell lines results in the precocious
      expression of myogenin, a muscle specific, helix-loop-helix factor that can trans
      activate muscle specific gene expression (G. Carnac et al., Mol. Endocrinol., 6:
      1185-1194, 1992). We have identified a T3 response element (TRE) in the mouse
      myogenin (MM) promoter between nucleotide positions -526 and -494 (5'
      GTGGTAGGTCTTTAGGGGTCTCATGGGACTGACA 3'). This sequence conferred appropriate
      hormonal regulation to an enhancerless SV40 promoter. Electrophoretic mobility
      shift analysis experiments showed that thyroid hormone receptor alpha (TR alpha)
      and retinoid X receptor alpha (RXR alpha) formed a heterodimeric complex on the
      MM TRE that was specifically competed by classical TREs and not by other response
      elements. Analyses of this heterodimer with a battery of steroid hormone response
      elements indicated that the complex was efficiently competed by a direct repeat
      of the AGGTCA motif separated by 4 nucleotides, as predicted by the 3-4-5 rule.
      Electrophoretic mobility shift analysis experiments showed that the myogenin,
      growth hormone, and myosin heavy chain TREs interacted with an identical nuclear
      factor(s) in muscle cells that was constitutively expressed during myogenesis.
      Mutagenesis of the MM TRE indicated that the sequence of the direct repeats
      (AGGTCA) and the 4-nucleotide gap were necessary for efficient binding to the TR
      alpha/RXR alpha heterodimeric complex. In conclusion, our data suggest that the
      MM TRE is a target for direct cross-talk between two different hormonal signals
      (T3 and 9-cis-retinoic acid) at the receptor level.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8297797
TI  - Biochemical characterization of peptide alpha-amidation enzyme activities of
      human neuroendocrine lung cancer cell lines.
AB  - Peptide alpha-amidation is a posttranslational modification of approximately half
      of all endocrine and neuroendocrine peptide hormones, including several hormones
      with mitogenic effects for tumor cells, and is typically essential for complete
      hormonal bioactivity. alpha-Amidated peptide hormones have been reported to be
      autocrine growth factors for small cell lung cancer cells. We report here that a
      variety of human lung tumor cell lines express both enzymes required for the two
      step conversion of inactive glycine-extended peptides into their active COOH
      terminal alpha-amide analogues. Human tumor cell peptidylglycine alpha-amidation
      enzymes are present in multiple molecular forms. Both proteins are metalloenzymes
      which are present at highest concentrations in secretory granules in
      neuroendocrine cell lines. The expression of these enzymes is positively
      correlated with expression of other markers of the neuroendocrine phenotype, such
      as DOPA decarboxylase. Peptidylglycine alpha-amidating enzyme-specific activities
      are approximately 50-fold higher in extracts of endocrine cell lines (lung small
      cell and carcinoid) than of nonendocrine lines. Biochemical characterization of
      the peptidylglycine alpha-amidating enzymes will enable development of tools for
      detection of endocrine processes in the early stages of neoplasia and for
      interruption of autocrine stimulation pathways in tumor cells.

PMID- 8297798
TI  - MEK2 is a kinase related to MEK1 and is differentially expressed in murine
      tissues.
AB  - MEK1 is a dual specificity kinase that phosphorylates and activates the Erk/MAP
      kinases Erk-1 and Erk-2 by phosphorylating them on threonine and tyrosine. We
      report the cloning of a second MEK-like complementary DNA, Mek2, which predicts a
      protein of a molecular weight of 44,500. The MEK2 protein bears substantial
      sequence homology to MEK1, except at its amino terminus, and at a proline-rich
      region insert between the conserved kinase subdomains 9 and 10. MEK1 and MEK2 are
      shown to be encoded by different genes and are located on murine chromosomes 9
      and 10, respectively. Northern analysis indicates that Mek2 is expressed at low
      levels in adult mouse brain and heart tissue, and at higher levels in other
      tissues examined. Low expression levels of Mek2 in brain tissue are in contrast
      to the high levels of Mek1 expressed in brain. Mek2 is expressed at high levels
      in neonatal brain, however. Recombinant MEK2 produced in bacteria phosphorylates
      a kinase-inactive Erk-1 on tyrosine and threonine, whereas a kinase-inactive
      mutant MEK2 does not. These findings suggest that MEK2 is a member of a multigene
      family.

PMID- 8297799
TI  - Molecular cloning of a unique complementary DNA of rat myosin regulatory light
      chain and its elevated expression in v-src-transformed rat culture cell lines.
AB  - We have isolated a complementary DNA (cDNA) clone, termed N14, from a cDNA
      library derived from normal rat fibroblast 3Y1 cells using a differential
      screening procedure. N14 cDNA was 1115 nucleotides in length and contained an
      open reading frame of 172 amino acid residues. The expression of N14 gene was
      significantly increased in Rous sarcoma virus-transformed 3Y1 cells (SR-3Y1)
      compared with that in parental 3Y1 cells. The high level of N14 gene expression
      was reduced by treatment with herbimycin A, indicating that the expression was
      dependent upon the activity of pp60v-src tyrosine kinase. A homology search
      revealed that the nucleotide sequence of N14 cDNA was nearly identical to that of
      the rat nonsarcomeric myosin regulatory light chain cDNA (RLC-B), with the
      exception of a 250-nucleotide insertion which is present between C at position
      +483 and G at position +484 in the RLC-B cDNA. Southern blot analysis indicated
      that N14 gene was present as a single copy in the rat genome. Therefore, these
      two mRNAs might be generated through the alternative splicing mechanism. However,
      a RNase protection assay revealed that RLC-B mRNA was not expressed in SR-3Y1
      cells. In addition, the amount of N14 mRNA was also increased in other types of
      transformed cells, including v-mos-, simian virus 40-, and v-Ha-ras-transformed
      3Y1 cells.

PMID- 8297800
TI  - Special issue dedicated to the memory of Professor John M. Cleghorn.

PMID- 8297801
TI  - Mothers of adult children with schizophrenia: an ethnographic study.
AB  - Most recent investigations of families of individuals with schizophrenia have
      been concerned with the negative impact of the family on the outcome for the ill
      relative. Although several investigators have documented the consequences of
      living with a mentally ill relative to family members, there is still a lack of
      research exploring the broader experience of family members including how they
      perceive and define the illness experience, and how they actively manage the
      situation. While mothers have been frequently identified as primary caregivers of
      mentally ill children, few investigators have explored the mother's perspective.
      A qualitative descriptive study was conducted to gain an understanding of the
      experience of mothers living with schizophrenic adult children. Ethnographic
      interviews conducted with five mothers were transcribed and subjected to
      qualitative analysis. The overall theme that emerged was a lifetime of mothering
      consisting of two major components, disruption and loss. Disruption was
      experienced in the mother's relations with the ill child, and in her own life. A
      lifetime of mothering involved two dimensions of loss: loss of the child's
      potential to lead a 'normal' life, and loss of freedom in the mother's own life.
      Central to mothers' descriptions was how they actively managed disruption and
      loss on a day-to-day basis.

PMID- 8297802
TI  - Influence of renal clearance on peripheral homovanillic acid measurements in
      healthy subjects and schizophrenic patients.
AB  - In order to investigate the effect of renal clearance on plasma homovanillic acid
      (HVA) concentrations, we examined plasma concentration and urinary excretion of
      HVA and creatinine per 4 h over 24 h in eight male schizophrenic patients and
      eight healthy male subjects. Renal clearances of HVA and of creatinine were
      determined per 4 h period. No significant differences were found between groups
      in the total 24 h excretion of either HVA or creatinine. Although differences
      between groups in plasma HVA concentrations and urinary HVA excretion per 4 h did
      not reach statistical significance, the renal clearance of HVA was significantly
      lower in the patient group than in the control group. There was no difference
      between groups in creatinine clearance. Diurnal changes were seen in the renal
      clearance of HVA and creatinine in both groups. Renal HVA clearance decreased
      from 23.00-07.00 h, with a coincident decrease in urinary HVA excretion and an
      increase in plasma HVA concentration. We provide evidence that renal clearance is
      an important determinant of plasma HVA concentration, and should be considered
      when interpreting plasma HVA data.

PMID- 8297803
TI  - Schizophrenia: impact of positive symptoms on gender social role.
AB  - A cross-sectional survey was conducted at one public and one private
      schizophrenia outpatient setting in the city of Sao Paulo, Brazil, in order to
      study gender differences in social disabilities. Sixty-nine patients who
      fulfilled DSM-III-R diagnostic criteria for schizophrenia were assessed by means
      of Brazilian versions of PANSS (Positive and Negative Syndrome Scale) and DAS
      (Disability Assessment Scale). Males presented an earlier onset of the disease
      and were less likely to have ever married. With respect to social disabilities,
      males fared worse than females on three items of DAS: self-care, under-activity
      and work performance. The adjusted scores of Section 1 (Overall Behavior) and
      Section 2 (Social Role Performance) were submitted to multiple regression
      analysis using the variables of sex, age of onset, age at examination,
      educational level, number of psychiatric admissions and the total scores of the
      positive and negative syndromes. Three variables explained a substantial part
      (45%) of the variance of overall behavior. These three were sex, age at
      examination, and negative syndrome total score. The higher the negative syndrome
      total score, the greater the disabilities for both sexes. Three variables
      explained 38% of the variance of social role performance. These were sex,
      negative symptoms and an interaction between sex and positive symptoms. The
      higher the negative syndrome total score, the greater the role impairment,
      regardless of sex. In women, but not in men, we found that the higher the
      positive syndrome total score, the greater the impairment in social role
      performance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297804
TI  - Three clinical syndromes of schizophrenia in untreated subjects: relation to
      brain glucose activity measured by positron emission tomography (PET).
AB  - A number of studies of chronically ill, medicated patients have found that the
      clinical symptoms of schizophrenia segregate into three syndromes which can be
      labelled poverty, disorganization, and reality distortion. It has been previously
      found that each of these syndromes is associated with a specific pattern of
      perfusion (rCBF) in paralimbic and association cortex and in related subcortical
      nuclei. We replicated the symptom factors in 20 untreated subjects. Utilizing
      positron emission tomography with 18-F-fluorodeoxyglucose as a tracer for glucose
      metabolism, we reconstructed a map of the entire cortical activity from 16 to 20
      tomographic slices. Each of the three syndromes was associated with a different
      pattern of regional glucose metabolism. Findings in common with previous studies
      were an association of poverty with left cortical metabolic activity in
      prefrontal and superior parietal areas, reality distortion with left temporal
      activity, and disorganization with left inferior parietal lobule. This is the
      first report of an association between regional metabolic activity and clinical
      syndromes in untreated patients, strengthening previous models of distributed
      neural networks in this disorder.

PMID- 8297805
TI  - Association of working memory deficit and eye tracking dysfunction in
      schizophrenia.
AB  - This study replicates our earlier findings that schizophrenic but not bipolar
      patients are impaired on oculomotor delayed response tasks, analogous to those
      used to assess spatial working memory functions of the dorsolateral prefrontal
      cortex (DLPFC) in monkeys (Park and Holzman, 1992). In addition, we examined the
      relation between working memory deficits and smooth pursuit eye movement (SPEM)
      dysfunction, since data from human neuropsychological and animal lesion studies
      implicate prefrontal pathology in both deficits. Schizophrenic patients showed
      marked deficits in the oculomotor memory task and the SPEM task relative to the
      control groups. However, they were not impaired on the oculomotor sensory task in
      which their responses were guided by external cues rather than by working memory.
      This result from outpatients replicates our earlier study which was conducted
      with inpatients. Within the schizophrenic group those patients with good eye
      tracking performed better than those with impaired pursuit on the oculomotor
      memory task but there was no correlation between SPEM and performance on the
      sensory task. These findings support the hypothesis that schizophrenics show a
      deficit in representational processes and add to the growing evidence for
      involvement of the dorsolateral prefrontal cortex in schizophrenic pathology.

PMID- 8297806
TI  - Size of the corpus callosum and auditory comprehension in schizophrenics and
      normal controls.
AB  - 19 schizophrenic patients and 15 normal controls, matched for sex and age, were
      evaluated by magnetic resonance imaging for corpus callosal size and had
      neuropsychological functioning assessed using an auditory comprehension test.
      Although the MRI data did not reveal any significant differences between groups,
      the degree of laterality to the left versus right ear response was significantly
      correlated with the size of the posterior part of the corpus callosum in male
      schizophrenics.

PMID- 8297807
TI  - Indirect semantic priming in schizophrenic patients.
AB  - Schizophrenic patients and normal controls performed a lexical decision task
      involving the recognition of words which were preceded (primed) by either
      associated, indirectly associated, or non-associated words. In contrast to normal
      control subjects who showed no indirect semantic priming effect at an inter
      stimulus interval (ISI) of 0 ms, a trend towards such an indirect semantic
      priming effect was found in schizophrenic patients. With a longer ISI of 500 ms,
      an indirect semantic priming effect was obtained in both groups. In the framework
      of network models of semantic memory, the results are interpreted as further
      evidence for an increase in activation or decrease in inhibition in the spreading
      of associational activation in schizophrenic patients.

PMID- 8297808
TI  - Schizotypal and paranoid personality disorder in the relatives of patients with
      schizophrenia and affective disorders: a review.
AB  - This review considers the possible familial relationship of schizotypal and
      paranoid personality disorders (SPD, PPD) to schizophrenia (SCZ) and affective
      disorders (AD). There have been few controlled studies on familial risk of SPD
      and PPD based on direct semi-structured interviews of relatives, blind to proband
      diagnosis. Three of six studies reported increased familial risk of SPD for SCZ
      probands, but with considerable variability in estimates of this risk. None of
      four studies reported a significant relationship between AD and familial SPD.
      There is substantial but less consistent evidence for a familial relationship
      between PPD and SCZ: three of six studies supported such a relationship, but one
      large study reported increased familial risk of PPD for AD and not for SCZ
      probands. There is also some evidence that negative symptoms are most
      characteristic of SPD in relatives of SCZ probands. Also discussed are issues
      concerning the adequacy of current criteria for defining schizophrenia spectrum
      pathology, and of diagnostic methods in this area.

PMID- 8297809
TI  - Positive and negative symptoms in families with schizophrenia.
AB  - Positive and negative symptoms are measurable characteristics that may represent
      core features of schizophrenia and offer a quantitative approach for studying the
      genetics of schizophrenia and related disorders. The Positive and Negative
      Syndrome Scale (PANSS) was used to assess 72 members of five families segregating
      schizophrenia. The study confirmed high internal reliability of PANSS scales in
      this sample with diverse lifetime diagnoses. Gender but not alcoholism affected
      scores. Schizophrenia/schizoaffective and schizophrenia spectrum disorder groups
      had higher mean scores for the positive and negative scales than other lifetime
      diagnostic groups, consistent with genetic transmission of these symptoms.
      Positive and negative symptom patterns did not subtype families. The results
      support the validity of positive and negative symptom measures as independent
      dimensions in familial schizophrenia.

PMID- 8297810
TI  - [Molecular mechanisms of sex steroid-induced growth of cancer cells].
AB  - Recent studies have suggested that the growth of sex steroid-dependent cancer is
      mediated through sex steroid-induced growth factors in an autocrine manner. In
      order to prove the hypothesis, estrogen-responsive human breast cancer cell lines
      such as MCF-7 have been used by many investigations. However, these studies have
      been unable to prove the hypothesis, since estrogen-dependent growth system in
      serum-free medium could not be established. We established in 1987 an androgen
      dependent growth system in a serum-free medium using androgen-dependent mouse
      mammary cancer cells (SC-3). By use of this androgen-dependent growth system in
      serum-free medium, we could demonstrate that androgen-dependent growth of SC-3
      cells is mediated via an androgen-induced new growth factor in fibroblast growth
      factor (FGF) family (AIGF; 8th member of FGF family) in an autocrine mechanism.

PMID- 8297811
TI  - Transgenic animal methodologies and their applications.
AB  - In the past 10 years the capacity has been acquired to genetically transform
      mammals via insertion of genes into developmentally totipotent embryonic cells.
      This profound advance has impacted significantly on our understanding of basic
      mechanisms of gene regulation, and has enabled practitioner's of this "transgenic
      technology" to establish important paradigms for the genetic engineering of
      experimental animals and livestock. The two most powerful forms of genetic
      engineering to emerge from this research include the targeted expression of
      foreign genes, or transgenes, and the ability to target specific endogenous mouse
      genes for mutagenesis. In this presentation I will outline the general principles
      underlying this technology, and provide examples of its use in research on cancer
      and aging that are ongoing in our laboratory.

PMID- 8297812
TI  - [Mechanism of loss of androgen dependency in androgen-dependent tumor].
AB  - Human prostatic cancer is androgen sensitive tumor but gradually loses its
      androgen sensitivity during progression. Amount of androgen receptors usually
      correlates with androgen sensitivity. Mutation of androgen receptor gene is
      attributable to be one reason for androgen insensitivity. Alternatively, it is
      shown that a murine androgen insensitive tumor derived from androgen dependent
      one possesses functional androgen receptors without structural abnormality. A
      series of gene mutation, especially with relation to genes encoding growth
      factors, may be an important change for progression from androgen sensitive tumor
      to insensitive one.

PMID- 8297813
TI  - [Molecular mechanism of androgen-dependent transformation--analysis using serum
      free culture system].
AB  - SC-3 cells, derived from androgen-dependent mouse breast cancer Shionogi
      carcinoma 115, have shown not only androgen-dependent growth stimulation but also
      morphological changes in serum-free culture. We have demonstrated that this
      androgen-dependent growth is mediated through an induction of heparin-binding
      growth factor (termed as androgen-induced growth factor: AIGF). We studied the
      molecular mechanism of androgen-dependent growth. NIH3T3 cells transfected to
      express AIGF showed focus-forming activity, anchorage-independent growth and
      tumor formation in nude mice indicating AIGF is an oncogene. The findings that
      AIGF inhibited binding of [125I]basic fibroblast growth factor (bFGF) and only
      FGF receptor (FGFR)-1 mRNA expressed in SC-3 cells suggested that AIGF acts
      through FGFR-1. Therefore, we cloned FGFR-1 from cDNA library of SC-3 cells,
      which was found to have three mutations. When this variant FGFR-1 was expressed
      in FGFR-negative myoblast L6 cells, AIGF-dependent inhibition of the
      differentiation to myocytes was observed suggesting that variant FGFR-1 is
      receptor of AIGF. Since expressions of c-myc mRNA as well as AIGF mRNA were
      induced by testosterone treatment, we studied the role of c-myc in androgen
      dependent growth in SC-3 cells using phosphorothioate derived antisense
      oligonucleotides (antisense) of c-myc or AIGF. Not only AIGF antisense but also c
      myc antisense inhibited androgen-dependent growth. c-myc antisense did not affect
      androgen-induced AIGF mRNA expression. c-myc antisense inhibited AIGF-, but not
      bFGF-induced DNA synthesis. These results suggest that c-myc has a critical role
      of AIGF-, but not bFGF-induced growth.

PMID- 8297814
TI  - [In vitro study for hormones and growth factors dependent cell proliferation of
      endometrial adenocarcinoma cells].
AB  - Sex steroid hormone dependent cell proliferation and inducing growth factors of
      endometrial carcinoma cells were investigated using in vitro culture systems. The
      cell proliferation of Ishikawa cells derived from well-differentiated endometrial
      adenocarcinoma which possess both estrogen and progesterone receptors were
      stimulated by either estradiol added to culture media or EGF and TGF-alpha acting
      through EGF receptors. These stimulatory effects of TGF-alpha were antagonized by
      the anti TGF-alpha and EGF-receptor antibodies. The cell proliferations of other
      endometrial cancer cells were also inhibited by those antibodies. All endometrial
      cancer cells secrete TGF-alpha into their culture media measured by TGF-alpha
      ELISA methods. The expression of TGF-alpha mRNA and secretion of TGF-alpha of
      Ishikawa cells were induced by estradiol but not of hormone independent HEC-50
      cells. Thus suggest that estradiol dependent growth factor should be TGF-alpha in
      human endometrial carcinoma cells.

PMID- 8297815
TI  - [Targeting therapy using monoclonal antibody directed against growth factor
      receptors].
AB  - Targeting therapy is expected to be a new effective anti-cancer treatment in near
      future. Major advances are achieved by considerable effort in this area.
      Monoclonal antibodies that recognize tumour-associated antigens were conjugated
      to chemotherapeutic drugs, toxins and radionuclides with various procedures. To
      apply this new therapy for clinical use, many problems still remain to be
      clarified. These problems consist of human anti-mouse antibody, antigenic
      heterogeneity and low tumour uptake. By our experiment, growth factor receptor
      was an ideal target for targeting therapy and immunoconjugate directed against
      growth factor receptor showed selective cytotoxicity to cancer cells with
      expression of growth factor receptor. Moreover, cytotoxic effect was positively
      correlated with expression level of growth factor receptor.

PMID- 8297816
TI  - [Mechanism of tumor cell invasion studied by a culture model--modification of
      invasiveness by host mediators].
AB  - A culture model for invasion of rat mesothelial cell layer by rat ascites
      hepatoma cells has been developed. By using this quantitative model, we have
      recently found that the invasiveness of tumor cells is not only genetically
      determined but is greatly influenced by their interactions with host cells and
      host mediators. The preculture with macrophages was found to enhance both the in
      vitro and in vivo invasive potentials of the tumor cells. This potentiation
      appears to be mediated partly by oxygen radicals generated by the cocultured
      macrophages. The in vitro invasive capacity was also augmented by pretreating the
      tumor cells with TGF-beta, or with activated platelets. In the in vitro invasion
      assay system, tumor cells did not invade against cultured mesothelial cell
      monolayers without fetal calf serum. Serum could be completely substituted by
      oleoyl-lysophosphatidic acid (LPA) or bacterial phospholipase D (PLD), suggesting
      a possible participation of particular signaling cascade, PLD-LPA(PA) system, in
      the invasion of certain tumor cells.

PMID- 8297817
TI  - [Migratory ability of cells derived from periodontal tissues and their attachment
      to root surfaces].
AB  - The migratory ability of cells from the periodontal ligament (PDL), alveolar bone
      and gingiva of monkeys was compared in vitro using a three-dimensional collagen
      gel model. In addition, the cell attachment to cementum and dentin was examined
      ultrastructurally. Cultured cells were obtained from monkey periodontal tissues
      using an explant method. Type I collagen solution was pipetted into the wells of
      24 multi-well plates and polymerized. And the cell invasion assay was performed
      by seeding test cells onto the gel, and subsequent culture for 1, 3 and 7 days.
      The specimens were fixed and embedded in epoxy resin. Semi-thin sections of 1
      micron thickness were obtained and subjected to visual assay under a light
      microscope. Parameter was two fold; numbers of cells migrating into the gel and
      the maximum distance from the gel surface to the leading front of migrated cells.
      Secondly, two kinds of root surface conditioning were performed on extracted
      monkey teeth, in which included scaling only surface cementum and root planing.
      Each root fragment was placed into the wells and collagen solution was
      subsequently pipetted into the well. And the collagen solution was polymerized to
      prepare the 100 microns-wide gel layers on the root fragments. Test cells were
      seeded onto the gel and cultured for 2 and 3 weeks. The interaction between the
      cells and the root surfaces was examined under a transmission electron
      microscope. The migratory ability of PDL cells was less than that of cells from
      bone and gingiva. Although the migrated bone and gingival cells produced
      fibrillar materials on the cementum, the PDL cells could not establish an ideal
      attachment to either cementum or dentin.

PMID- 8297818
TI  - Establishment and characterization of a human neuroblastoma cell line derived
      from a brain metastatic lesion.
AB  - We encountered a case of abdominal primary stage IV neuroblastoma which recurred
      in the central nervous system. A neuroblastoma cell line, designated KP-N-NS, was
      established from this brain metastatic lesion. This is considered to be the first
      neuroblastoma cell line established from a brain metastatic lesion. In culture,
      KP-N-NS exhibited N(neuroblastic) type cell morphology with neurite-like
      processes and small cell bodies. This cell line revealed karyotypic abnormality,
      46, XX, -1, +der (1)t(1;?)(p36.1;?), and twelve-fold amplification of MYCN DNA
      (twice as much in primary bone marrow tumor cells). Integrin study indicated high
      expression levels of alpha 1 beta 1 and alpha 4 beta 1, but alpha 2 beta 1, alpha
      3 beta 1, alpha 5 beta 1, alpha 6 beta 1, alpha 6 beta 4, and alpha v beta 3 were
      barely detectable by fluorescence-activated cell sorting (FACS) analysis.
      Compared with 8 other previously established N-type neuroblastoma cell lines, no
      significantly characteristic integrin expression was detected in this cell line.
      KP-N-NS will provide a useful tool for the study of metastasis and relapse in the
      central nervous system in neuroblastoma patients.

PMID- 8297819
TI  - Characterization of epidermal growth factor (EGF) receptor and biological effect
      of EGF on human uterine cervical adenocarcinoma cell line OMC-4.
AB  - In this paper, we investigated how epidermal growth factor (EGF) acts on growth
      and regulation of extracellular matrix components and their degenerative enzymes
      in uterine cervical adenocarcinoma cells in vitro. Effects of EGF on cell growth,
      DNA synthesis, and laminin, collagen IV, and tissue plasminogen activator (t-PA)
      production of human uterine cervical adenocarcinoma cell line OMC-4 were
      examined, together with the characteristics of its EGF receptors. Scatchard plot
      of EGF binding to OMC-4 indicated two classes of binding sites with a
      dissociation constant of 170 pM and 510 pM. The total binding sites were 1.6 x
      10(5)sites/cell. The number of OMC-4 cells did not increase in the presence of
      EGF, whereas 3H-thymidine incorporation was inhibited by EGF at concentrations of
      1 and 10 nM. The production of laminin and collagen IV by OMC-4 cells was
      inhibited by EGF, whereas that of t-PA was significantly promoted at the
      physiological concentration of 0.1 nM. These results suggest that EGF is closely
      associated with regulation of proliferation and extracellular matrix degradation
      of uterine cervical adenocarcinoma cells.

PMID- 8297820
TI  - [Establishment of a human lung squamous cell carcinoma cell line LK-17, and
      characterization of procoagulant, platelet aggregation and metastatic potential].
AB  - A squamous cell carcinoma cell line LK-17 was established from original surgical
      specimen of the lung. Doubling time of LK-17 in vitro is 43.2 hours, and
      chromosome analysis shows various abnormality and main modeat 62. LK-17 shows
      stable metastatic potential to the lung of nude mouse when injected i.v. LK-17
      cells show platelet aggregating activity with number population dependent manner.
      LK-17 secretes direct factor X activating procoagulant which differs from those
      of tissue factor, cystein protease A and coagulant cancer antigen 1. These
      platelet aggregation potential and procoagulant activity may play a important
      roll in metastatic process.

PMID- 8297821
TI  - [Comparative genomic hybridization(CGH)].
AB  - A new molecular cytogenetic method, comparative genomic hybridization(CGH), was
      reviewed. CGH produces a map of DNA sequence copy number on a normal metaphase
      spread after hybridization with the mixture of tumor DNA and normal reference
      DNA, which are detected with different fluorochromes, respectively. Then the
      ratio of two fluorochromes are analysed with digital image analyzer and reveals a
      real copy number of the DNA sequences. CGH surveys entire chromosomes at a time
      and would clarify oncogenes and tumor suppressor genes, which had not known.

PMID- 8297822
TI  - Poly(ethylene oxide) star molecules: synthesis, characterization, and
      applications in medicine and biology.

PMID- 8297823
TI  - Festschrift in honor of the 60th birthday of Dr. Allan S. Hoffman. Part 3.

PMID- 8297824
TI  - Properties controlling the diffusion and release of water-soluble solutes from
      poly(ethylene oxide) hydrogels. 2. Dispersion in an initially dry slab.
AB  - The mechanisms which control the release of dispersed water-soluble drugs from an
      initially dry hydrogel are complex. The release profile derives from a
      combination of several contributing factors which may change with time at
      different rates. It has been possible to isolate controlling factors and
      investigate their individual contributions to the release kinetics. The hydrogels
      presented in this paper owe their hydrophilicity to their poly(ethylene oxide)
      content. They swell and can absorb up to three times their dry weight in water.
      Having a glass transition temperature (Tg) below body temperature they are
      essentially different to those studied theoretically or experimentally, by other
      groups, which have Tg values above body temperature and are initially glassy. A
      range of diffusates was studied ranging from low water-soluble prostaglandin E2
      to highly water-soluble lithium chloride. Device geometry was restricted to
      approximations to infinite slabs with more than 85% total surface area over the
      top and bottom surfaces so that release was predominantly one-dimensional and the
      controlling variable was thickness. The increase in surface area with time, drug
      solubility in the water-swelling matrix and the presence of crystallinity were
      shown to be important factors governing the profile and level of release rate
      with time. It was observed that the release profile could be separated into three
      parts, the most important being the middle section from early in the release
      until at least the half-life time. This period could be characterized by the
      exponential time function, tn. The diffusional exponent, n, is an important
      indicator of the release mechanism and ranged from 0.79 to 1, i.e. good anomalous
      to zero order. This is a highly desirable range of values for controlled release
      devices. The value of n decreases at late-time. The very early-time release can
      also show a burst or lag effect depending on the diffusate solubility and its
      loading in the xerogel.

PMID- 8297825
TI  - Patterned neuronal attachment and outgrowth on surface modified, electrically
      charged fluoropolymer substrates.
AB  - Fluorinated ethylenepropylene copolymer (FEP) and polyvinylidene fluoride (PVDF)
      can generate static and transient electrical charges, respectively, after bulk
      molecular rearrangements induced by electrical charging techniques. Neurons
      cultured on electrically active FEP and PVDF show increased levels of nerve fiber
      outgrowth compared to electrically neutral material. The purpose of the present
      study was to determine if the addition of charged surface groups to the surfaces
      of FEP and PVDF would modify the influence of bulk electrical charges on cultured
      neurons. Mouse neuroblastoma (Nb2a) cells were cultured on electrically charged
      and uncharged FEP and PVDF substrates with covalently modified surfaces
      containing hydroxyl (OH) and amine (NH2) groups. Surface chemical modification
      was performed on the entire surface or in discrete striped regions. Nb2a cells
      cultured on electrically active FEP and PVDF showed greater levels of
      differentiation than cells on electrically neutral substrates. The presence of
      NH2 groups attenuated these responses in serum-containing media. Cells attached
      to NH2 rich surfaces generally displayed a flatter morphology and tended to
      remain attached for longer time periods. Cells cultured on stripe-modified
      substrates in serum-containing media showed a strong preferential attachment to
      modified regions, especially on NH2 stripes. In summary, bulk electrical charges
      are more important than surface charges in stimulating Nb2a cell differentiation.
      Surface groups serve to modulate neuronal morphology and confer specific
      attachment promoting properties in serum-containing media. The development of an
      optimal neuronal regeneration template may require the incorporation of specific
      bulk and surface properties.

PMID- 8297826
TI  - Molecular surface tailoring of biomaterials via pulsed RF plasma discharges.
AB  - A pulsed RF plasma glow discharge is employed to demonstrate molecular level
      controllability of surface film deposits. Molecular composition of plasma
      deposited films is shown to vary in a significant manner with the RF duty cycle.
      Three fluorocarbon monomers are used to illustrate the process. All three exhibit
      a trend towards increased surface CF2 content with decreasing pulsed RF duty
      cycle, including exclusion of oxygen. Significant variations in carbon-fluorine
      surface functionalities are obtained over a controllable range of film thickness.
      Film growth rate measurements reveal the occurrence of surface reactions during
      significant portions of the off portion of the duty cycle. Albumin adsorption on
      fluorocarbon-treated PET films is unchanged from PET controls for a 100-fold
      range of bulk concentrations and 60-fold range of adsorption times. However,
      increased retention of albumin is observed following incubation with protein
      denaturing sodium dodecyl sulfate solution, the retention decreasing with
      increasing bulk concentration of albumin. The increased retention of albumin
      suggests the treated surfaces may have promise as biocompatible materials.

PMID- 8297827
TI  - Ultrasonically enhanced transdermal drug delivery. Experimental approaches to
      elucidate the mechanism.
AB  - The effect of therapeutic range ultrasound on skin permeability was studied in
      vitro. Permeating molecule ionization state, pH, ultrasound duration,
      reversibility of the enhancement phenomenon, and skin structural alterations were
      evaluated. It was found that ultrasound affects the permeability of both ionized
      and unionized molecules. No irreversible structural alterations due to the
      ultrasound exposure were detected in the stratum corneum. Ultrasound enhancing
      mechanism was discussed.

PMID- 8297828
TI  - Synthesis and nonthrombogenicity of fluoroalkyl polyetherurethanes.
AB  - New polyetherurethanes carrying fluoroalkyl substituents in the side chains were
      synthesized from N,N-di(hydroxyethyl)heptadecafluorooctyl-sulfonamide (a chain
      extender), 4,4'-disocyanatodiphenylmethane, and poly(tetramethylene glycol).
      Various kinds of polyetherurethanes having different tensile properties were
      prepared by changing the content of fluoroalkyl chain extender or the molecular
      weight of poly(tetramethylene glycol). The surface of a film made from the
      fluoroalkyl polyetherurethane was strongly water-repulsive. The in vitro thrombus
      formation on the fluoroalkyl polyetherurethanes was reduced by increasing the
      content of chain extender for the same molecular weight of poly(tetramethylene
      glycol). Protein adsorption, platelet adhesion, and platelet activation on the
      fluoroalkyl polyetherurethanes were also investigated.

PMID- 8297829
TI  - Activity of horseradish peroxide adsorbed on radio frequency glow discharge
      treated polymers.
AB  - Horseradish peroxidase (HRP) has been used as a model enzyme in this study of its
      physical adsorption and residual enzyme activity on radio frequency glow
      discharge (RFGD)-treated polymers. The specific enzymatic activity of HRP
      adsorbed on different surfaces was assumed to be an indication of the extent of
      its conformational alterations on the surfaces. The surfaces studied were poly
      (ethylene terephthalate) (PET), polytetrafluoroethylene (PTFE), and
      tetrachloroethylene and tetrafluoroethylene glow discharge-treated PET,
      abbreviated as TCE/PET and TFE/PET. All surfaces were characterized by electron
      spectroscopy for chemical analysis (ESCA) and liquid contact angles in air. HRP
      adsorbs more strongly onto the two discharge-treated surfaces than onto the
      untreated polymers, as evidenced by the lower amount of HRP eluted by sodium
      dodecyl sulfate (SDS) from the treated polymers. For example, seventy percent of
      the HRP adsorbed on TCE/PET or TFE/PET remains on the surface after overnight
      elution with a 1% solution of SDS. In contrast, untreated PET and PTFE each
      retains only c. 20% of the absorbed enzyme. The enzymatic activity of HRP
      adsorbed on the different surfaces was studied using hydrogen peroxide (H2O2) as
      the substrate. HRP adsorbed on the higher energy surfaces, PET and TCE/PET,
      retains significantly more activity than the HRP adsorbed on the lower energy
      surfaces, PTFE and TFE/PET which appear to destroy rapidly almost all of the
      activity of HRP after it adsorbs. HRP adsorbed on TCE/PET is relatively more
      stable over time than HRP adsorbed on PET or free HRP in solution. (For example,
      only 45% of the specific enzymatic activity of HRP adsorbed on TCE/PET was lost
      after 3 h of storage in phosphate buffer at 37 degrees C, while 70% of that
      adsorbed on PET was lost.) In summary, when HRP is adsorbed on TCE/PET, it is
      very tightly bound, and yet it maintains a significant fraction of its initial
      specific activity and also retains this activity for 3 h in phosphate buffer at
      37 degrees C. Thus, tenacious physical adsorption of proteins such as enzymes on
      TCE glow discharge-treated surfaces may have potential as a new method of
      immobilization of such molecules, for uses in biosensors, diagnostics,
      bioseparations, cell culture and bioreactors.

PMID- 8297830
TI  - Covalent immobilization of microorganisms in polymeric hydrogels.
AB  - A method of covalent immobilization of microorganisms (marine luminescent
      bacteria and yeast) in polymeric hydrogels is described. It is shown that cell
      immobilization leads to the creation of materials having properties of both
      synthetic polymers and physiologically active systems. Application of systems
      containing covalent immobilized yeast and photobacteria in biotechnological and
      other processes is proposed.

PMID- 8297831
TI  - Controlled release of TGF-beta 1 from a biodegradable matrix for bone
      regeneration.
AB  - Although bone has a remarkable capacity for regenerative growth, there are many
      clinical situations in which the bony repair process is impaired. TGF-beta 1 is a
      25 kD homodimeric protein which modulates the growth and differentiation of many
      cell types. The ability of TGF-beta 1 to promote bone formation suggests that it
      may have potential as a therapeutic agent in disease of bone loss. However, there
      still exists a need for an effective method of delivering TGF-beta 1 to the site
      of an osseous defect for the promotion of bone healing. This paper describes a
      novel biodegradable controlled release system for TGF-beta 1 comprised of poly
      (DL-lactic-co-glycolic acid) (PLPG) and demineralized bone matrix (DBM). The
      amount and activity of TGF-beta 1 released was determined using several methods
      including 125I-labeled TGF-beta 1 as a tracer, an enzyme linked immunosorbent
      assay (ELISA) and a growth inhibitory assay (GIA). Protein was released from the
      devices for time periods of more than 600 h. The amount of TGF-beta 1 released
      was directly proportional to both the TGF-beta 1 loading and the weight percent
      of DBM in the device. The release kinetics could be further controlled by
      applying polymeric coatings of varying porosity to the devices. The GIA indicated
      that between 80 and 90% of the TGF-beta 1 released from the delivery system
      retained its bioactivity. The PLPG and DBM existed in phase separated domains
      within the device as determined by differential scanning calorimetry. Scanning
      electron microscopy suggested that the devices were sufficiently porous to allow
      bone ingrowth.

PMID- 8297832
TI  - Synthesis and application of new microcarriers for animal cell culture. Part I:
      Design of polystyrene based microcarriers.
AB  - In this work (Part I), surface modified styrene polymers as new microcarrier
      material for animal cell culture were extensively investigated. The first
      synthesis steps--carried out by chloromethylation, sulphonation and nitration of
      the polystyrene matrix--resulted in precursors with a defined surface layer
      thickness. The obtained hydrophobic bulk phase showed a limited absorption of
      hydrophilic media components compared to polysaccharides matrices like dextran.
      By varying reaction conditions for microcarrier synthesis and/or by using similar
      styrene type polymer matrices like polyvinyltoluene, the specific density (1.028
      1.05 g/cm3) of the microcarrier matrix was adjusted without problems. Chemical
      varying of the microcarrier surface by reaction of the precursors with different
      amines, saccharides or proteins led to new microcarriers with optimal conditions
      for cell adhesion and cell growth. All biological investigations were carried out
      with a BHK 21 (c-13) cell line. Detailed results will be discussed and summarized
      in Part II of this work.

PMID- 8297833
TI  - Synthesis and application of new microcarriers for animal cell culture. Part II:
      Application of polystyrene microcarriers.
AB  - In this work (Part II) the application of new polystyrene based microcarriers in
      cell culture technology is demonstrated. Carriers with a variety of surface
      modifications were tested as a growth support for cell line BHK 21. The growth
      behavior of the cells and cell to surface attachment were compared to Cytodex 3
      (Pharmacia), which was used as a reference carrier. To select carriers with
      growth supporting surfaces, broad screening in petri dish experiments was carried
      out. Candidates with the highest growth rates were investigated in spinner flash
      experiments in further detail. Polystyrene carrier with a surface modification
      like triethylamine, maltamine or N-methylglucosamine were able to support growth
      as good or better as the reference carrier Cytodex 3. Economies of ingredients
      and ease in laboratory handling could make amine-modified polystyrenes a
      competitive alternative to currently commercially available microcarrier types.

PMID- 8297834
TI  - A novel biomaterial: poly(dimethylsiloxane)-polyamide multiblock copolymer I.
      Synthesis and evaluation of blood compatibility.
AB  - Aramid-silicone resins (PASs) consisting of aromatic polyamide (aramid) and
      poly(dimethyl-siloxane) (PDMS) segments were synthesized by low temperature
      solution polycondensation. For the evaluation of blood compatibility in vitro,
      two kinds of experiments were carried out. One was the thromboxane B2(TXB2)
      release test from platelets attaching to PAS and Biomer. The other was the
      observation of the platelet adhesion on the surfaces of PAS by scanning electron
      microscopy (SEM). The results indicated that PAS was bio-inert in vitro. The
      surface chemical composition of PAS films was investigated by means of electron
      probe micro analysis (EPMA), X-ray photoelectron spectroscopy (XPS), and dynamic
      contact angle measurements. The relationship between blood compatibility and
      surface composition of PAS is discussed.

PMID- 8297835
TI  - Fibroblast contraction of collagen matrices with and without covalently bound
      hyaluronan.
AB  - Hyaluronan, which is found in high concentrations in fetal tissues, has been
      suggested to play a major role in preventing scar formation in fetal wounds. We
      have developed a floating collagen fibrillar matrix (CFM) made out of
      reconstituted type I collagen for the purpose of evaluating the ability of
      hyaluronan to inhibit the fibroblast induced contraction of the matrix. When
      hyaluronan is covalently bound to collagen it appears to better support
      fibroblast proliferation and matrices are less contractible by these cells than
      when hyaluronan interacts only ionically. When hyaluronan is bridged between
      collagen fibrils by a network of extensive covalent crosslinks, contractibility
      by fibroblasts is abolished. These modified collagen matrices may prove to be
      very useful in the development of bioprostheses and implants.

PMID- 8297836
TI  - Changing childbirth. Commentary I.

PMID- 8297837
TI  - Changing childbirth. Commentary II.

PMID- 8297838
TI  - The sexual behaviour of young people.

PMID- 8297839
TI  - The myth of fetal growth retardation at term.

PMID- 8297840
TI  - Hypersecretion of luteinising hormone: a significant cause of infertility and
      miscarriage.

PMID- 8297841
TI  - Nifedipine versus ritodrine for suppression of preterm labour.
AB  - OBJECTIVE: To compare the efficacy of tocolysis with specific regimens of
      nifedipine and ritodrine. Maternal side effects and neonatal outcome also were
      evaluated. DESIGN: A prospective, randomised trial. SUBJECTS: Seventy-one women,
      including 11 with twin pregnancies, who had uterine contractions and observed
      cervical changes. MAIN OUTCOME MEASURES: Prolongation of pregnancy for 48 h,
      seven days and until 36 weeks of pregnancy were evaluated for each treatment.
      Maternal side effects and haemodynamic changes were compared, as well as neonatal
      outcomes. RESULTS: Delivery was delayed for 48 h, seven days, and until the 36th
      week of gestation in 83%, 67%, and 50%, respectively, of women in the nifedipine
      group, compared with 77%, 63% and 43%, respectively, of women in the ritodrine
      group (no significant difference). Maternal side effects were significantly less
      common in the ritodrine group (no significant difference). Maternal side effects
      were significantly less common in the nifedipine group (27%) than in the
      ritodrine group (77%) (P < 0.001). The neonatal outcome was similar in the two
      groups. The fall in mean arterial and diastolic blood pressure, and the rise in
      maternal heart rate were significantly greater in the women who received
      ritodrine compared with those treated with nifedipine. CONCLUSIONS: Nifedipine is
      as effective as ritodrine in suppressing preterm labour. Its use is associated
      with less frequent side effects.

PMID- 8297842
TI  - The interrelationship of eclampsia, HELLP syndrome, and prematurity: cofactors
      for significant maternal and perinatal risk.
AB  - OBJECTIVE: To determine if there are differences between mothers and fetuses in
      eclamptic pregnancies with or without concurrent HELLP syndrome. DESIGN:
      Retrospective review. SETTING: A single tertiary perinatal centre, the University
      of Mississippi Medical Center. SUBJECTS: All eclamptic pregnancies treated during
      a 141 month period from 1980 until the end of 1991. METHODS: Pregnancies were
      grouped according to the presence or absence of HELLP syndrome subclassified as
      class 1 = platelet nadir < or = 50,000/microliters, class 2 = platelet nadir >
      50,000 to < or = 100,000/microliters, and class 3 = platelet nadir > 100,000 to <
      or = 150,000/microliters. RESULTS: Among 49,782 live births, there were 117 women
      with eclampsia prior to delivery (incidence 1:425), 62 of which had HELLP
      syndrome. The group with HELLP syndrome were delivered significantly earlier
      (32.1 vs 36.4 weeks), and had lower birthweights (1821 vs 2550 grams) and higher
      perinatal mortality (113 vs 18:100). They were also transfused more frequently
      (65% vs 35%), and suffered greater overall serious maternal morbidity and
      mortality. CONCLUSION: Eclampsia is more likely to be associated with the HELLP
      syndrome at early gestations. Although eclamptic patients are already at risk,
      the presence of HELLP syndrome accentuates the risk for adverse maternal
      perinatal outcome.

PMID- 8297843
TI  - The coagulation system in placental insufficiency: a study in the fetal
      circulation.
AB  - OBJECTIVE: To examine the hypothesis that Doppler-defined umbilical placental
      insufficiency is associated with intravascular coagulation in the fetal
      circulation. DESIGN: A prospective, descriptive, single centre study. SETTING:
      The University of Sydney, Department of Obstetrics at Westmead Hospital.
      SUBJECTS: Ninety-one infants were classified on the basis of the
      systolic:diastolic (SD) ratio of the umbilical artery flow velocity waveforms
      into severe (SD > 99.9th centile), moderate (SD > 95th centile) or control
      groups. INTERVENTION: Blood was collected from the umbilical vein at delivery.
      MAIN OUTCOME MEASURES: The coagulation variables measured were the plasma
      concentrations of thrombin-antithrombin, fibrinopeptide A and fibrinogen, the
      antithrombin III activity, the prothrombin time and the activated partial
      thromboplastin time. RESULTS: There were no differences in activated partial
      thromboplastin time, antithrombin III activity, fibrinopeptide A or thrombin
      antithrombin complex concentrations between fetuses with placental insufficiency
      and those with no placental disease. Fetuses with severe and moderate placental
      insufficiency had a statistically significant prolongation of their mean
      prothrombin time compared to controls (23.7 +/- 0.8, 23.6 +/- 1.6, and 19.9 +/-
      0.6 s, respectively). Infants in the severe group had a lower plasma fibrinogen
      concentration than control fetuses (1.66 +/- 0.09 and 1.94 +/- 0.09 g/l,
      respectively). The activated partial thromboplastin time and antithrombin III
      activity were both highly dependent on gestational age. CONCLUSIONS: These
      results do not support the hypothesis that Doppler-defined umbilical placental
      insufficiency is associated with activation of coagulation in the fetal
      circulation.

PMID- 8297844
TI  - A loading model for ritodrine administration in preterm labour.
AB  - OBJECTIVE: To develop a ritodrine infusion scheme for preterm labour that avoids
      plasma levels above those needed for tocolysis, requires only one rate
      adjustment, and is easy to apply in practice. DESIGN: Prospective study of
      tocolytic effect and plasma ritodrine concentrations during application of the
      infusion scheme. SETTING: High risk labour ward. SUBJECTS: Consecutive series of
      31 women in labour at less than 36 weeks' gestation. INTERVENTION: Loading dose
      ritodrine infusion followed, as soon as tocolysis is reached, by a decrease in
      the infusion rate calculated on the basis of the interval between start of
      treatment and tocolysis. RESULTS: Overall, steady state ritodrine levels were
      nearly identical to those at the time of tocolysis and correlated well with
      levels anticipated on the basis of our calculation (n = 30; r = 0.91; P < 0.001).
      Adjustments during steady state were made in 12 women (40%), but in only two of
      them within 12 h after tocolysis had been reached. Delivery was postponed for
      more than 48 h in 29 women (93.5%) and beyond 37 weeks' gestation in 19 (61.3%).
      CONCLUSION: The loading model is easy to apply, avoids relative overdoses,
      requires few adjustments, is well tolerated, uses smaller quantities of
      ritodrine, and results in lower plasma ritodrine concentrations than the
      conventional infusion scheme.

PMID- 8297845
TI  - Plasma oestrogens in postmenopausal women with endometrial cancer.
AB  - OBJECTIVE: To study plasma levels of estrogens and androgens, sex hormone-binding
      globulin (SHBG) and follicle stimulating hormone (FSH) in postmenopausal patients
      with endometrial cancer. DESIGN: Patients and controls were matched for age, body
      mass index, parity and years since menopause. SETTING: Department of Obstetrics
      and Gynaecology, Hvidovre Hospital, Denmark. SUBJECTS: Fifty postmenopausal
      patients with endometrial cancer and 54 matching controls. MEASUREMENTS: Plasma
      levels of SHBG, FSH, oestrone, oestradiol, oestrone-sulphate, dehydro
      epiandrosterone sulphate, testosterone, and androstenedione were measured by
      radio-immunoassays. Free fractions of oestradiol and testosterone were calculated
      according to levels of SHBG and albumin. RESULTS: The levels of oestradiol, free
      oestradiol, and oestrone were elevated (P < 0.001) in patients compared with
      controls (oestradiol: 51 (45-59) vs 37 (34-41) pmol/l; free oestradiol: 0.69
      (0.59-0.80) vs 0.48 (0.42-0.54) pmol/l; oestrone: 180 (159-204) vs 119 (107-133)
      pmol/l (mean values (95% CI) in patients vs controls)). Furthermore, an increased
      oestrone:androstenedione ratio (0.095 vs 0.072, P < 0.01) was found in patients.
      SHBG correlated negatively (P < 0.001) with body mass, while the free fractions
      of oestradiol and testosterone correlated positively (P < 0.01) with body mass,
      in both patients and controls. Multiple regression analysis showed that the
      differences in oestrogen levels between the two groups persisted when controlling
      for the effect of body mass, age, years since menopause, parity, and levels of
      SHBG and FSH. CONCLUSION: Patients with endometrial cancer exhibit increased
      plasma levels of oestradiol and oestrone. Speculatively, these oestrogens may
      result from an increased oestrone conversion from androstenedione, an increased
      ovarian and adrenal secretion of androstenedione, or alternative oestrogen
      production routes. The present findings support the hypothetical role for
      oestrogens in the aetiology of endometrial cancer.

PMID- 8297846
TI  - Differential diagnosis of ovarian cancer with tumour markers CA 125, CA 15-3 and
      TAG 72.3.
AB  - OBJECTIVE: To determine the accuracy of tumour associated antigens CA 125, CA 15
      3 and TAG 72.3 in the differential diagnosis of benign and malignant pelvic
      masses and to compare the results with a previously defined risk of malignancy
      index (RMI). DESIGN: Retrospective analysis of samples collected during a
      prospective observational study. SETTING: Department of Obstetrics and
      Gynaecology, the Royal London Hospital and Duke University Medical Center.
      SUBJECTS: One hundred and forty-three consecutive patients undergoing surgery for
      an adnexal mass. METHOD: Tumour marker levels were determined by radio
      immunoassay in stored serum samples obtained from 143 study subjects. RESULTS:
      The highest diagnostic accuracy of the tumour marker panel was achieved by
      defining a positive result as elevation of any two of CA 125 (> 30 u/ml), CA 15-3
      (> 30 u/ml) and TAG 72.3 (> 10 u/ml), (sensitivity 66.7%, specificity 93.1%).
      Similar diagnostic accuracy could be achieved by CA 125 alone using an upper
      limit of 50 u/ml (sensitivity 66.7%, specificity 94.1%). Inclusion of CA 15-3 or
      TAG 72.3 in stepwise logistic regression analysis did not improve the
      discriminative performance of the RMI. CONCLUSION: The risk of malignancy index
      incorporating CA 125, menopausal status and ultrasound is superior to the panel
      of three tumour markers for pre-operative differential diagnosis of the pelvic
      mass.

PMID- 8297847
TI  - Distribution of mast cells and the effect of their mediators on contractility in
      human myometrium.
AB  - OBJECTIVE: To examine the distribution of mast cells in human uterine tissue and
      to study the interactions between mast cell mediators (histamine and serotonin)
      and PGF2 alpha in human myometrium contractile activity. DESIGN: Distribution of
      mast cells were analysed in cryostat sections of myometrium samples stained with
      Toluidine blue. Contractile activity was evaluated in an isolated organ bath
      preparation on myometrial strips obtained from women whose pregnancies ended in
      elective caesarean section. SETTING: Biological Science Laboratories at the
      University of Concepcion. SUBJECTS: Twenty women undergoing elective caesarean
      and 10 women undergoing hysterectomy at the G. Grant Hospital. MAIN OUTCOME
      MEASUREMENTS: Cumulative concentration-response curves for histamine and
      serotonin before and after the addition of subumbral concentrations of the PGF2
      alpha or serotonin were performed. RESULTS: Serotonin was more active than
      histamine to evoke contractions (EC50:0.20 (SE 0.02) mumol/l vs 1.5 (SE 0.2)
      mumol/l, respectively). Furthermore, threshold concentrations of serotonin (0.05
      mumol/l) potentiated the contractile effect of histamine (EC50:0.3 (SE 0.06)
      mumol/l and 50% increase in E(max)). PGF2 alpha had a poor contractile effect,
      but threshold concentrations (0.05 and 0.10 mumol/l) enhanced the contractile
      effect of both serotonin and histamine. A population of mast cells was found in
      close apposition to smooth muscle fibres. CONCLUSIONS: It is postulated that the
      simultaneous release of mast cell mediators (histamine and serotonin) in
      myometrium could be an important stimulus for evoking strong contractions in the
      human uterus. PGF2 alpha may have indirect effects in myometrium by amplifying
      the effects of histamine and serotonin.

PMID- 8297848
TI  - An audit of general practitioner requests for pelvic ultrasound: analysis of
      referral patterns and outcome.
AB  - OBJECTIVES: 1. To assess the information supplied by general practitioners on the
      gynaecological ultrasound request form and to determine how this information
      influences the interpretation of scans; and 2. To examine the influence of scans
      on the subsequent management of patients both by general practitioners and, where
      relevant, by hospital gynaecologists. DESIGN: Retrospective analysis of
      gynaecological ultrasound requests made by general practitioners. Postal
      questionnaire and assessment of outcome according to general practitioners'
      records and, where appropriate, the hospital notes. SETTING: A London teaching
      hospital gynaecological ultrasound department and associated general practices.
      SUBJECTS: Four hundred ninety-eight women referred by general practitioners for a
      gynaecological ultrasound scan over a one year period (1990). RESULTS: The 498
      requests for gynaecological ultrasound scans included 472 primary diagnostic
      referrals. Seventy-one percent of general practitioners replied to the
      questionnaires. Overall, 46% of the scans were normal, but the proportion of
      normal scans fell to 21% if the date of the last menstrual period and a pregnancy
      test result were included on the form. Forty per cent of women scanned
      subsequently were referred for hospital care. CONCLUSIONS: General practitioners
      would appear to use the ultrasound service in a rational way and therefore there
      can be no justification for not allowing them open access. The positive
      diagnostic yield can be further improved if time is taken to supply simple
      relevant information which may be facilitated by a specific request form.

PMID- 8297849
TI  - Common variable hypogammaglobulinemia in pregnancy.

PMID- 8297850
TI  - Pregnancy in a patient on chronic haemodialysis: fetal monitoring by Doppler
      velocimetry of the umbilical artery.

PMID- 8297851
TI  - Balloon valvuloplasty for congenital aortic stenosis in pregnancy.

PMID- 8297852
TI  - Primary complete colporrhexis in primigravida.

PMID- 8297853
TI  - Cardiomyopathy of pregnancy.

PMID- 8297854
TI  - The predictive value of outpatient hysteroscopy in a menopause clinic.

PMID- 8297855
TI  - Sex ratios in the families of women ascertained by a toxaemic pregnancy.

PMID- 8297856
TI  - Postpartum haemorrhage in Zimbabwe: a risk factor analysis.

PMID- 8297857
TI  - Simplifying laparoscopic surgery for ectopic pregnancies.

PMID- 8297858
TI  - Rising beta-hCG titres following laparoscopic injection of methotrexate into
      unruptured, viable tubal pregnancies.

PMID- 8297859
TI  - Final report of the MRC/RCOG randomised controlled trial of cervical cerclage.

PMID- 8297860
TI  - Epidural analgesia: not just one technique.

PMID- 8297861
TI  - Failure to progress in the management of labour.

PMID- 8297862
TI  - Effect of the prostaglandin E1 analogue gemeprost on the blood flow velocity
      waveforms of uterine arteries during the first trimester of pregnancy.
AB  - OBJECTIVE: To investigate the effect of the vaginal application of the
      prostaglandin (PGE1) analogue gemeprost on the vascular resistance of the main
      uterine arteries in early pregnancy. DESIGN: A prospective observational study.
      SUBJECTS: Twenty-one patients seeking legal termination of pregnancy at 7-12
      weeks gestation. METHODS: Pulsatility indices for the main uterine arteries were
      measured by vaginal colour Doppler ultrasound before and 3 to 4 h after vaginal
      application of the PGE1 analogue gemeprost. RESULTS: A significant increase of
      pulsatility indices was observed (P < 0.001) which was not affected by parity or
      gestational age. The change was similar in both uterine arteries, and placental
      lateralisation did not affect the results. All fetuses were still alive at the
      second examination. CONCLUSIONS: Vaginal application of prostaglandin analogue
      gemeprost in early pregnancy increases the vascular resistance of uterine
      arteries. This may be caused by a direct vasoconstrictory effect or be secondary
      to uterine contractions.

PMID- 8297863
TI  - Pudendal nerve damage during labour: prospective study before and after
      childbirth.
AB  - OBJECTIVE: To establish the effect of childbirth on pudendal nerve function and
      identify obstetric factors associated with such damage. DESIGN: A prospective
      investigational study. SETTING: Antenatal clinic, St Bartholomew's (Homerton)
      Hospital. SUBJECTS: One hundred and twenty-eight unselected pregnant women beyond
      34 weeks' gestation. INTERVENTION: Pudendal nerve terminal motor latencies
      (PNTML) and perineal plane were measured during pregnancy and six to eight weeks
      after delivery, and remeasured in a subgroup (n = 22) at six months. MAIN OUTCOME
      MEASURES: Effect of mode of delivery on PNTML and the plane of the perineum.
      RESULTS: Vaginal delivery resulted in a significant (P < 0.0001) prolongation of
      the mean PNTML bilaterally in both primipara (n = 57) 1.91 ms (SD 0.19) vs 2.00
      ms (SD 0.22), antenatal vs postnatal, right PNTML; 1.96 ms (SD 0.21) vs 2.06 ms
      (SD 0.24) left PNTML, and multipara (n = 32) (P < 0.01). Perineal descent during
      straining was also increased after vaginal delivery (P < 0.001). Greater damage
      to the pudendal nerve occurred on the left side (P = 0.03). PNTML were not
      altered after elective caesarean section (n = 7), but were increased on the left
      side when caesarean section was performed during labour (1.94 ms (SD 0.13) vs
      2.08 ms (SD 0.29), P < 0.01). A heavier baby and a longer active second stage of
      labour were both associated with significant prolongation of PNTML. Eight out of
      12 women with a prolonged PNTML at six weeks had normal measurements when
      restudied six months after delivery. CONCLUSION: Vaginal delivery, particularly
      the first, results in significant pelvic floor tissue stretching and pudendal
      nerve damage. Women who have a caesarean section during labour may also be at
      risk of pudendal nerve damage. The process of labour and vaginal delivery can
      both cause pudendal nerve damage which may be asymmetrical in extent.

PMID- 8297864
TI  - Charts of fetal size: 1. Methodology.
AB  - OBJECTIVES: To discuss the features of study design and analysis which are
      necessary to derive valid reference centiles for fetal size. To describe a study
      which meets the stated criteria. DESIGN: Prospective study of 663 fetuses.
      RESULTS: The selection of the sample and adequate sample size are of great
      importance. Prospective collection of data specifically for the purpose of
      deriving centiles is recommended. It is essential to use statistical methods that
      take proper account of the increasing variation among fetuses as pregnancy
      proceeds; such methods are described and illustrated. A study is described which
      meets the stated criteria for design and analysis, and from which new fetal size
      centile charts have been derived and are presented in subsequent papers.
      CONCLUSIONS: Many published studies containing charts (standards) of fetal size
      are methodologically flawed. Research design and statistical analysis must adhere
      to sound principles for fitted centiles of size to be valid and so clinically
      relevant.

PMID- 8297865
TI  - The efficacy of synthetic adhesion barriers in infertility surgery.

PMID- 8297866
TI  - Charts of fetal size: 2. Head measurements.
AB  - OBJECTIVE: To construct new size charts for fetal head circumference, biparietal
      diameter and other head dimensions. DESIGN: A prospective, cross sectional study.
      SETTING: The routine ultrasound department of a London teaching hospital.
      SUBJECTS: The fetuses of 663 women seen in the routine antenatal booking clinic
      whose ultrasound and menstrual dates agreed within 10 days. METHODS: Fetuses were
      scanned once only for the purpose of the study at gestations between 12 and 42
      weeks, when up to 20 dimensions were measured. For each measurement separate
      regression models were fitted to estimate the mean and standard deviation at each
      gestational age. Centiles were derived by combining these two regression models,
      assuming that the measurements have a normal distribution at each gestational
      age. RESULTS: A total of 594 fetuses had their biparietal diameter measured and
      their head circumference measured directly. Both head diameters were recorded for
      587 fetuses and the circumference was also derived from these, as was the
      cephalic area. New charts are presented for biparietal diameter (both outer-outer
      and outer-inner), head circumference (directly measured and derived from
      diameters). The directly measured head circumferences were consistently (by about
      1%) greater than those derived from measurement of the head diameters. The new
      charts are compared with previously published charts that are in wide use. Charts
      for occipitofrontal diameter, cephalic index and cephalic area are also
      presented. CONCLUSIONS: We have constructed new size charts for the fetal
      biparietal diameter and for head circumference, both measured directly and
      derived from head diameters. We have demonstrated the difference between the size
      charts constructed from these two sets of values and hence the importance of
      using the appropriately derived chart when assessing the head circumference. The
      differences between the new charts for biparietal diameter and head circumference
      and previous ones may be largely due to methodological differences.

PMID- 8297867
TI  - Relation between frequency of uterine contractions and human fetal cerebral
      oxygen saturation studied during labour by near infrared spectroscopy.
AB  - OBJECTIVE: To investigate the effect of the frequency of uterine contractions on
      fetal cerebral oxygenation, using near infrared spectroscopy. DESIGN: An
      observational study relating changes in the fetal cerebral concentrations of
      oxyhaemoglobin and deoxyhaemoglobin, measured from the start of one contraction
      to that of the next, to the time interval between contraction peaks observed by
      external tocography. SETTING: A teaching hospital obstetric and neonatal unit.
      SUBJECTS: Ten term fetuses during labour. RESULTS: Changes in cerebral
      oxyhaemoglobin concentration were positively, and in deoxyhaemoglobin negatively,
      correlated with the time interval between contractions (P < 0.001). A mean
      contraction interval of 2.3 min was found below which the concentration of
      oxyhaemoglobin usually fell and that of deoxyhaemoglobin rose, indicating a fall
      in cerebral haemoglobin saturation. Conversely, longer contraction intervals were
      associated with findings indicative of a rise in cerebral haemoglobin saturation.
      CONCLUSION: Short contraction intervals (< 2.3 min) were associated with a
      decrease, and longer contraction intervals with an increase in fetal cerebral
      oxygen saturation. Contractions occurring repeatedly at intervals less than 2.3
      min are likely to result in progressive cerebral desaturation.

PMID- 8297868
TI  - Cigarette smoking and histological outcome in women with mildly dyskaryotic
      cervical smears.
AB  - OBJECTIVE: To determine which patient related variables, available at the point
      of referral, predict the presence of high grade intraepithelial neoplasia when
      the smear result is mild dyskaryosis with or without co-existent koilocytosis.
      DESIGN: Multivariate analysis of prospective programme trial. SETTING: Academic
      Department Colposcopy clinics at Dudley Road Hospital, Birmingham, UK. SUBJECTS:
      One hundred and sixty-seven women, whose worst ever cervical smear was mild
      dyskaryosis with or without koilocytosis, referred to colposcopy clinics. All the
      women had complete data sets, as determined by the format of an ongoing
      programme, and all were treated by diathermy loop excision of the cervical
      transformation zone. MAIN OUTCOME MEASURES: Age, parity, contraceptive practice,
      smoking habit, duration of abnormal cytology and the grade of histology in the
      excised transformation zone. RESULTS: Forty-seven out of 78 (60%) smokers,
      compared with 18 out of 73 (25%) nonsmokers, had high grade disease. The other
      variables considered in the analysis were not significant or very weakly
      associated with histological grade when analysed in a univariate analysis.
      Stepwise logistic regression identified cigarette smoking as a powerful
      independent predictor of high grade disease. CONCLUSION: These data suggest a
      strong association between smoking and high grade intraepithelial neoplasia in a
      population of women whose worst ever smear report was mild dyskaryosis. Smoking
      is a variable that could be built into models to facilitate referral for
      colposcopic assessment.

PMID- 8297869
TI  - The incidence of vaginal bleeding with tibolone treatment.
AB  - OBJECTIVE: To determine the incidence of breakthrough bleeding and its
      significance in recently postmenopausal women who take tibolone (Livial-Organon).
      DESIGN: A two year comparative nonrandomised prospective study of women taking
      tibolone (2.5 mg) and control subjects not on medication. SETTING: Teaching
      hospital menopause and well women clinic. SUBJECTS: One hundred women who were
      recently menopausal (between 6 and 36 months since last menstrual period). Fifty
      were commenced on tibolone and 50 received no medication. MAIN OUTCOME MEASURES:
      Episodes of bleeding throughout the two year study period were recorded.
      Oestradiol levels were measured at baseline and at six, 12 and 24 months. The age
      of menopause and time since last menstrual period (LMP) were noted. RESULTS:
      Twenty percent (12/59) (95% CI 11.0% to 32.8%) of women in the tibolone group had
      breakthrough bleeding compared with 9.4% (5/23) (95% CI 3.1% to 20.7%) in the
      control group. Of the women who bled in the tibolone group, 50% had LMP between
      six and 12 months prior to entering the study, and 83% were younger than the
      average age of menopause. Sixty-seven percent had detectable oestradiol levels on
      at least one occasion over the two years (five women had detectable oestradiol
      levels and did not bleed). None had evidence of endometrial stimulation at
      dilatation and curettage. Eighty percent of women who bled in the control group
      were between six and 12 months since LMP on entry into the study, and 80% had
      detectable oestradiol levels during the study. At dilatation and curettage there
      was no evidence of endometrial stimulation. CONCLUSIONS: A minority of women will
      bleed on tibolone therapy. Women who are likely to bleed are younger, are
      recently menopausal, and may have remaining endogenous oestrogen production.

PMID- 8297870
TI  - The effects of maternal vascular pressure on the dimensions of the placental
      capillaries.
AB  - OBJECTIVE: The study sought stereological evidence for the sluice flow phenomenon
      in the human term placenta. DESIGN: Two series of experiments were conducted on
      caesarean delivered placentae. In both, two fetal arteries were cannulated and
      perfused. In the first series, five placentae were perfusion-fixed under arterial
      pressures of 40 mmHg and 60 mmHg, and an external pressure of 10 mmHg in the
      intervillous space. In the second series, five placentae were perfusion-fixed at
      arterial pressures of 70 mmHg and 90 mmHg with an external pressure of 30 mmHg.
      Stereological estimates relating to the size of the capillaries and the thickness
      of the villous membrane were then made. RESULTS: In each series, as the arterial
      pressure rose, there was an increase in the volume fraction and surface area of
      the fetal capillaries, and a concomitant decrease in the mean thickness of the
      villous membrane. These changes were negated as the external pressure rose,
      indicating the importance of the pressure differential between the capillary
      lumen and the intervillous space in determining the dimensions of the fetal
      capillaries. CONCLUSIONS: The study demonstrated that placental capillaries are
      elastic and hence deformable. If a sufficiently high pressure is generated in the
      intervillous space, they may therefore be compressed. This may explain the
      increase in umbilical vascular resistance demonstrated by doppler studies in
      pregnant women scanned in the supine position. In this situation the venous
      drainage from the intervillous space is believed to be impeded by the gravid
      uterus compressing the inferior vena cava.

PMID- 8297871
TI  - Low molecular weight heparin for obstetric thromboprophylaxis.

PMID- 8297872
TI  - Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy.

PMID- 8297873
TI  - Validation of automated blood pressure recording in pregnancy.

PMID- 8297874
TI  - The use of low molecular weight heparin for thromboprophylaxis in pregnancy.

PMID- 8297875
TI  - Postpartum eclampsia associated with ergometrine maleate administration.

PMID- 8297876
TI  - Myomectomy in the treatment of postpartum haemorrhage.

PMID- 8297877
TI  - Unexplained haemolytic anaemia in successive pregnancies with negative direct
      antiglobulin test and response to high dose i.v. IgG.

PMID- 8297878
TI  - Branch retinal artery occlusion in pregnancy.

PMID- 8297879
TI  - Conservative management of placenta accreta.

PMID- 8297881
TI  - Hormone replacement therapy and breast cancer.

PMID- 8297880
TI  - Asymptomatic women at high risk of vertical HIV-1 transmission to their fetuses.

PMID- 8297882
TI  - Is obstetric and neonatal outcome worse in fetuses who fail to reach their own
      growth potential.

PMID- 8297883
TI  - Is obstetric and neonatal outcome worse in fetuses who fail to reach their own
      growth potential?

PMID- 8297884
TI  - Obstetric intervention and economic imperative.

PMID- 8297885
TI  - Caesarean section--public versus private. Why the differential? A reply to
      obstetric intervention and the economic imperative.

PMID- 8297886
TI  - The use of the fetal electrocardiogram in labour.
AB  - It is clear that considerably more work needs to be done before fetal ECG
      waveform analysis can be adopted for the purposes of routine fetal monitoring. It
      must be decided exactly what we want fetal ECG waveform analysis to achieve. If
      it is to reduce the number of operative deliveries performed in the presence of
      normal or intermediate CTG patterns then the fetal ECG shows promise, but its
      physiological significance in this context remains uncertain. If fetal ECG
      analysis is to be related to outcome, as opposed to events in labour, then
      several very large well conducted randomised prospective controlled trials will
      be needed. At present a large multicentre study (European Community Concerted
      Action Project 1989) is taking place in which a large number of intrapartum ECG
      records are being collected, blinded to the clinician and stored onto optical
      disc via a personal computer. A multicentre study in the United Kingdom using the
      Nottingham system is also being planned. We need await the outcome of these to
      verify if any of a variety of fetal ECG variables can be related to outcome. It
      behoves us to validate fetal ECG analysis against outcome measures that truly
      indicate whether the labour process has compromised or damaged the fetus. We must
      not fall into the trap of yet again wholeheartedly embracing a test that has not
      been properly validated.

PMID- 8297887
TI  - [Transmission electron microscopic ultrastructure of the tegument of Fibricola
      seoulensis].
AB  - An electron microscopic study was performed to observe the ultrastructure of the
      tegument of F. seoulensis. The outer surface of the tegument was covered with a
      trilaminated plasma membrane. The electron-dense cytoplasmic layer was 2.5
      microns wide in the anterior portion and contained numerous vacuoles,
      mitochondria and granular materials in its matrix. The basement layer was 330 nm
      wide or so, and its numerous extensions protruded into the cytoplasmic layer. The
      sensory organ was composed of a small vesicle of 1.7 x 1.1 microns in dimensions,
      which possessed a cilium of 1.2 x 0.19 micron in size. The pharynx was composed
      of the epithelial layer of about 0.5 micron wide, well developed muscle layer and
      basement layer. The tegument of the oral sucker was composed of a cytoplasmic
      layer of 0.4-0.5 micron width, a narrow basement layer, a well developed muscle
      layer and tegumental cells. Some kinds of secretory granules that seemed to be
      originated from the cells of the oral sucker were observed in the parenchymal
      portions of the adjacent cells. The tribocytic organ consisted of numerous
      microvilli. The microvilli were 5 nm wide and heptalaminated. Two types of
      secretory granules originated from the gland cells of tribocytic organ were
      observed in the tegument and parenchyme. The tegumental cells were irregular in
      shape, and of which nuclei were multifarious.

PMID- 8297888
TI  - Transmission electron microscopic findings of the tribocytic organ of Fibricola
      seoulensis.
AB  - We observed ultra-structure of the tribocytic organ of Fibricola seoulensis with
      transmission electron microscope. Microvilli are observed on the surface of the
      tribocytic organ. Below the muscle layer, we can find three types of cells. Type
      I cell has electron lucent cytoplasm with a few granules, while type II cell
      shows electron dense cytoplasm and the particulate granules. Type III cell's
      electron dense cytoplasm possesses many granules. Of the above three cells, Type
      I and II cells are believed as tegumental cells. Type III cells are thought as
      glandular cells specific to the tribocytic organ. This finding can also explain
      the secretory function of the tribocytic organ of F. seoulensis.

PMID- 8297889
TI  - [The nervous system of Fibricola seoulensis by acetylcholinesterase
      histochemistry].
AB  - F. seoulensis were obtained from artificially infected albino rats at 3, 4, 5, 6,
      7 days after infection. The worms and metacercariae were washed in physiological
      saline solution, and fixed with 10% neutral formalin. The acetylcholinesterase
      (AchE) stained by enzyme histochemistry using acetylthiocholine iodide as
      substrate. Eserine, iso-OMPA and BW284C51 were used as inhibitors of AchE. The
      nervous system consists of three pairs longitudinal nerve trunks interconnected
      with excretory plexus in posterior half, and pharynx and oral sucker in anterior
      half of metacercariae and adults. The longitudinal nerve trunks are
      interconnected with transverse commissures and numerous circular commissures.
      Considerable numbers of circular commissures are interconnected with longitudinal
      nerve trunks lying on the surface of the worms. At each stage of juvenile worms,
      AchE and nonspecific cholinesterase activities were observed in the oral sucker,
      ventral sucker, pharynx and nerve system. Isozymes of AchE in F. seoulensis were
      separated into the two bands, 69 kDa and 132 kDa. The major band was 69 kDa.

PMID- 8297890
TI  - [Intestinal flukes of genus Metagonimus and their second intermediate hosts in
      Kangwon-do].
AB  - This study investigate the epidemiological feature of Metagonimus infection in
      Kangwon-do (province). The average infection rate of the surveyed inhabitants was
      7.8% (83 positives out of 1, 067 examinees) by stool examination; male, 11.4% and
      female, 3.2%, respectively. The egg positive rate in residents in the Som river
      area was 7.3%, that of the Chuchon river area 6.3%, the Pyongchang river area
      12.8%, the Tong river area 3.8%, the Hongchon river area 9.8%, and the Ohsip
      stream area of Samchok 8.0%, respectively. The average metacercarial infection
      rate of genus Metagonimus in the fish was 81.0% (256 positives out of 318 fish).
      The infected fishes were Zacco platypus, Zacco temmincki, Opsariichthys bidens,
      Squalidis sp., Carassius carassius, etc. in western Kangwon-do Meanwhile, in the
      Ohsip stream area of Samchok-gun, eastern costal Kangwon-do, the infected fish
      were Plecoglossus altivelis and Tribolodon hakonensis. The rats and dogs are
      infected with the metcercariae obtained from Zacco platypus and Opsariichthys
      bidens, adult worms collected were Miyata type of Metagonimus with some M.
      takahashii. When infected with metacercariae from Plecoglossus altivelis,
      Metagonimus yokogawai was only found. M. yokogawai and Metagonimus Miyata type
      were found together in Tribolodon hakonensis in Ohsip stream area of Samchok, in
      the eastern Kangwon-do. The intestinal flukes of genus Metagonimus in western
      Kangwon-do were Miyata type of Metagonimus and M. takahashii, transmitting mainly
      by Zacco platypus and Opsariichthys bidens as a source of infection. In the
      eastern part of Kangwon province (Ohsip stream area of Samchok), M. yokogawai was
      mainly distributed by P. altivelis and T. hakonesis, but some T. hakonensis
      harbored the metacercariae of Miyata type of Metagonimus with those of M.
      yokogawai.

PMID- 8297891
TI  - [Seasonal distribution of chigger mites in the Kanghwa Island and Yongjong
      Island].
AB  - Seasonal distribution of chigger mites in the Kangwha Island and Yongjong Island
      was studied during the period of October 1992-August 1993. From 42 field rodents
      collected, 1,290 chiggers were obtained and 8 species of 4 genera were
      identified. In the Kanghwa Island, Leptotrombidium pallidum was the predominant
      species through all seasons with the percentage of 93.0%. Whereas, in the
      Yongjong Island, L. palpale was the predominant species with the percentage of
      38.4% and L. pallidum was not found.

PMID- 8297892
TI  - Larval Gnathostoma nipponicum found in the imported Chinese loaches.
AB  - Six early third-stage larvae of Gnathostoma nipponicum were recovered from the
      muscle of 376 loaches, Misgurnus anguillicaudatus, imported from China. They were
      614 x 114 microns in average size, almost colorless except brownish intestine,
      and encircled by about 229 transverse rows of minute cuticular spines. Their head
      bulbs provided with 3 rows of hooklets, of which average number were 34.5 on the
      first, 36.7 on the second and 39.7 on the third. Accordingly, it is revealed that
      the Chinese loach is a natural second intermediate host of G. nipponicum and G.
      nipponicum has been distributed somewhere in China. This parasite may infect
      human when the imported loaches are consumed raw.

PMID- 8297893
TI  - [Localization and isozyme patterns of phosphatase in Fibricola seoulensis].
AB  - The present study was carried out to investigate the localization and isozyme
      patterns of acid phosphatase and alkaline phosphatase in metacercariae and in
      adults of F. seoulensis by enzyme-histochemistry method and electrophoresis. Acid
      phosphatase showed a strong activity at pH 5 in the intestinal caecum of adults,
      but showed no reactions in the non-substrate control and in the inhibitor-treated
      control. Alkaline phosphatase showed a strong activity at pH 8 in the intestinal
      caecum and the tribocytic organ of adults, and in the intestinal caecum and in
      the genital anlagen of metacercariae. In non-denature PAGE, ten bands of protein
      fraction from the extracts of metacercariae and twenty-two bands from adults were
      detected. In denature PAGE, two protein bands having molecular weights of 192 kDa
      and 123 kDa were detected in the metacercariae, but absent from adult stage. In
      adults, protein fractions of 27.5 kDa, 24.5 kDa, 21.4 kDa, 18 kDa, 16 kDa and 15
      kDa were detected. In non-denature PAGE, isozymes of acid phosphatase showed the
      most strong activity at pH 5, whereas no activity was shown at pH 2 and pH 7. One
      isozyme band (62 kDa) of AcPase was recognized in metacercariae and 4 isozyme
      bands (95 kDa, 85 kDa, 73 kDa and 62 kDa) in adults.

PMID- 8297894
TI  - [Prophylactic effects of trimethoprim-sulfamethoxazole in Toxoplasma-infected
      mice].
AB  - This study was performed to evaluate the prophylactic effects of trimethoprim
      sulfamethoxazole (TMP-SMZ) in mice experimentally infected with virulent RH
      strain and avirulent Beverley strain of T. gondii. The mice infected with 1 x
      10(5) tachyzoites were used in the measurement of mean survival days, and the
      mice infected with 10 cysts were used in the titrations of specific antibodies
      and enumeration of brain cysts. Mean survival days of mice were significantly
      increased in mice treated with TMP-SMZ as compared with spiramycin-treated and
      untreated control group. Mean survival days and survival rates of mice were
      increased according to the increment of dosages, and TMP-SMZ protected 100% of
      mice after fifteen daily dose of 24 mg/mouse or more administered orally.
      Toxoplasma-specific serum IgG and IgM antibody titers were significantly lower in
      mice treated with TMP-SMZ than those of spiramycin-treated and untreated control
      group. Toxoplasma cysts were not found in mice treated with TMP-SMZ at a dose of
      24 mg/mouse or more per day, but the group of spiramycin treatment and untreated
      controls were found in the brain from 20 days after infection. The present
      results revealed that TMP-SMZ can be used as a prophylactic agent against murine
      toxoplasmosis after intraperitoneally challenges with the virulent or avirulent
      strain of T. gondii.

PMID- 8297895
TI  - Intestinal parasites of cats purchased in Seoul.
AB  - Fecal samples of cats purchased in Seoul were examined for helminth ova or
      protozoan oocysts from December 1987 to March 1988. Out of the 41 samples, 31
      (75.6%) were positive and 60 (146.3%) were cumulative positive for parasites. The
      followings were identified in the samples: Eggs of Toxocara cati, Clonorchis
      sinensis, Metagonimus sp., Pharyngostomum cordatum, Spirometra erinacei, Taenia
      taeniaeformis and oocysts of Isospora sp. From nine autopsied cats, larvae of
      Anisakis simplex, adults of C. sinensis, M. yokogawai, P. cordatum, S. erinacei
      and T. taeniaeformis were identified. This is the first report on the detection
      of Anisakis larvae from cats in Korea. The possible role of cats as a source of
      human infection with each parasite was discussed.

PMID- 8297896
TI  - Intestinal parasite infections in the inhabitants along the Hantan River, Chorwon
      gun.
AB  - The prevalence of intestinal parasite infections in inhabitants at the reaches of
      the Hantan River, Chorwon-gun, Korea, was observed from August 12 to September
      14, 1993. Of 465 people observed by cellophane thick smear and formalin-ether
      concentration method, 2 Ascaris lumbricoides (unfertilized), 1 Trichuris
      trichiura, 39 Clonorchis sinensis and 16 Metagonimus egg positive cases were
      found. After treatment, the Metagonimus egg positive cases passed out flukes of
      Metagonimus Miyata type. Of 68 fish caught in the Hantan River, 14 (20.6%) were
      infected with metacercariae of Metagonimus, while no metacercaria of C. sinensis
      was found. At this area, soil-transmitted nematodes are very low, but
      clonorchiasis and metagonimiasis are prevalent by modernate endemicity.

PMID- 8297897
TI  - Inhibition of entry of Toxoplasma gondii into MDCK cells by fetal bovine serum.
AB  - We experienced the partial inhibition of entry of Toxoplasma gondii into MDCK
      cells when the FBS was depleted from media. MDCK cells and Toxoplasma (RH strain)
      were co-cultured, the penetration was inhibited up to 60-80% with concentration
      dependence of FBS. Inhibitory effect was clear when the conc. of FBS was over 1%
      (v/v) with 50% inhibition conc. of 5%. When Toxoplasma was pre-incubated with FBS
      and then applied to MDCK cells, there were no inhibitory effect, but when FBS was
      added to Toxoplasma-MDCK co-culture, the time of adding was critical with rapid
      inhibition. And when FBS was further treated with heat (95 degrees C, 10 min),
      the inhibitory effect was decreased slightly in both raw and inactivated FBS. The
      FBS factor(s) might participate to neutralize secreted materials which enhancing
      penetration or intervene between receptor-ligand binding at the moment of entry
      through sterically rather than functionally.

PMID- 8297898
TI  - Loss of human leukocyte antigen expression on colorectal tumor cell lines:
      implications for anti-tumor immunity and immunotherapy.
AB  - A system devised for tissue typing the human leukocyte antigen-A (HLA-A) locus
      from genomic DNA by the polymerase chain reaction (PCR) has been used to
      investigate abnormalities of HLA expression in a panel of 30 cell lines derived
      from colorectal adenocarcinomas, by comparison of the HLA-A locus genotype with
      surface expression of HLA. Eleven cell lines gave single HLA-A locus specificity
      on PCR typing, suggesting that loss of HLA alleles is a common abnormality. In
      one of these cell lines the loss of an HLA-A locus allele was confirmed by
      comparison with DNA from a lymphoblastoid B cell line derived from the same
      patient. In three cell lines, loss of expression of an HLA-A locus determinant
      was observed in spite of the presence of the relevant allele in genomic DNA.
      Three cell lines showed absent HLA expression associated with failure to express
      beta 2-microglobulin. These data indicate that at least three independent
      mechanisms were involved in the loss of HLA expression on the colorectal tumor
      cell lines.

PMID- 8297899
TI  - Role of major histocompatibility complex class I alpha 1/alpha 2 domain
      polymorphism and in vivo expression pattern in tumor resistance: studies with
      transgenic mice and lymphoma cell transfectants.
AB  - The influence of major histocompatibility complex (MHC) class I molecules on
      target cell sensitivity and natural killer cell specificity was investigated. H
      2b lymphoma cells grew progressively in syngeneic nontransgenic C57Bl/6 (B6)
      mice, but were rapidly rejected (within 24 h) in H-2Dd transgenic B6 mice (D8).
      Rejection required transgene expression in hematopoietic tissues, as revealed in
      experiments using transgenic mice with tissue-specific expression of the
      transgene into the target cells as well as bone marrow chimeric mice. The
      rejection was abrogated by transfection of the H-2Dd gene, providing evidence of
      "missing self" recognition in vivo triggered by a single class I allelic
      difference between host and graft. Lymphoma cells transfected with nonrelated
      class I molecules (H-2Dp and H-2Ld) did not lead to escape from rejection in D8
      mice. Furthermore, transfection with exon shuffled constructs between H-2Dd and H
      2Ld allowed mapping of the "protective" parts of H-2Dd. Only the transfectant
      expressing the alpha 1/alpha 2 domains of H-2Dd (the alpha 3 domain of H-2Ld)
      escaped elimination in D8 mice, while the transfectant expressing the opposite
      exon shuffled gene (the alpha 1/alpha 2 domains of H-2Ld in connection with the
      alpha 3 domain of H-2Dd) was rejected like the nontransfected wild type. The
      results showed that (a) introduction of a novel MHC class I gene in transgenic
      mice altered the specificity of natural killer cells, and (b) protection from
      transgenic NK cells required expression of the alpha 1/alpha 2 domains of H-2Dd
      at the target level.

PMID- 8297900
TI  - Molecular mechanisms used by tumors to escape immune recognition:
      immunogenetherapy and the cell biology of major histocompatibility complex class
      I.
AB  - In this article, we explore the hypothesis that tumor cells can escape
      recognition by CD8+ T cells via deficiencies in antigen processing and
      presentation. Aspects of the molecular and cellular biology of major
      histocompatibility complex class I are reviewed. Evidence for histology-specific
      molecular mechanisms in the antigen-processing and -presentation deficiencies
      observed in some human and murine tumors is presented. Mechanisms identified
      include down-regulation of antigen processing, loss of functional beta 2
      microglobulin, and deletion of specific alpha-chain alleles. Finally, we discuss
      studies using an antigen-presentation-deficient mouse tumor as a model for the
      immunogenetherapy of an antigen-presentation deficiency.

PMID- 8297901
TI  - Antigen processing: where tumor-specific T-cell responses begin.
AB  - It is well established that tumor-specific CD8+ T cells have the capacity to
      prevent and cure malignancies in animals under experimental conditions. This has
      raised expectations that it will prove possible to achieve similar successes with
      human cancers. CD8+ T cells recognize peptides of 8-10 residues derived from
      cytosolic proteins that are bound to the class I molecules of the major
      histocompatibility complex. To most effectively manipulate the T-cell response to
      tumor cells, it is essential to understand the means by which the peptide-class I
      complex is created in cells. An overview of this process is provided with an
      emphasis toward the recent findings made by our laboratory.

PMID- 8297902
TI  - Tumor cells expressing major histocompatibility complex class II and B7
      activation molecules stimulate potent tumor-specific immunity.
AB  - In previous studies we have shown that the highly malignant mouse SaI sarcoma can
      be converted into an immunogenic tumor that is immunologically rejected by the
      autologous host if the tumor cells are transfected with and express syngeneic
      major histocompatibility complex (MHC) class II genes. Tumor cells expressing
      class II heterodimers truncated for the cytoplasmic regions of the alpha and beta
      chains, however, are as malignant as wild-type class II- tumors. These studies
      have contributed to the hypothesis that T-cell activation requires two signals:
      the engagement of the MHC class II/peptide complex of the antigen-presenting cell
      (APC) by the T cell receptor for antigen of the responding T cell and the
      transmittal of a second, or costimulatory, signal by the APC to the responding T
      cell. In this report we show that induction of tumor-specific immunity is
      facilitated by delivery of a costimulatory signal provided by the B7 activation
      molecule. Mice challenged with SaI cells bearing truncated class II molecules and
      transfected with B7 cDNA are immune to the transfectants and are protected
      against a challenge of wild-type class II-B7- ascites or solid SaI tumor. The
      induced immunity requires CD4+ T cells and is specific for the immunizing sarcoma
      cells. These results highlight the critical role of the B7 costimulatory pathway
      in stimulating long-term, tumor-specific immunity that is effective against high
      doses of challenging wild-type tumor and suggest a strategy for enhancing tumor
      rejection.

PMID- 8297903
TI  - Tumor-bearing animals contain suppressed antitumor effectors the function of
      which can be unmasked by IL-2.
AB  - CMS5 fibrosarcoma cells were infected with retroviral constructs containing
      interleukin-2 (IL-2) cDNA and selected in G418. Parental tumor cells and those
      that produced IL-2 were injected in vivo. Whereas injection of parental tumor
      cells resulted in progressive tumor growth, those secreting high levels of IL-2
      were rejected. Furthermore, the immunosuppression associated with inoculation of
      parental tumor cells was not seen. To understand the failure of mice to reject
      non-IL-2-secreting tumor cells, functional responses of spleen cells from immune
      and tumor-bearing mice were studied in vitro. As expected, immune spleen cells
      proliferated under a variety of conditions but were inhibited in the presence of
      parental tumor cells. Even spleen cells from tumor-bearing animals responded well
      in the absence of parental tumor cells or in the presence of parental tumor
      cells, if supplied with adequate levels of IL-2. These results suggest that both
      tumor-bearing and immune mice generate antitumor effectors but that the cells
      might be functionally suppressed because of their inability to secrete IL-2 after
      contact with parental tumor cells.

PMID- 8297904
TI  - Role of T-cell tolerance in the persistence of hepatitis B virus infection.
AB  - Infants born to hepatitis B e antigen (HBeAg)-positive hepatitis B virus (HBV)
      carrier mothers invariably become persistently infected. To investigate the role
      of immunologic tolerance mechanisms in chronic infection of the newborn, we have
      generated HBeAg-expressing transgenic mice (B10.S-Tg31e). These mice were
      tolerant to both HBeAg and the nonsecreted HBcAg at the T-cell level.
      Furthermore, nontransgenic littermates born to HBeAg-expressing mothers showed
      lowered T-cell responses to HBc/HBe antigens, suggesting that tolerogenic HBeAg
      may cross the placenta. Tg mice did not produce antibody to HBeAg but did produce
      immunoglobulin M (IgM) antibodies to HBcAg via a T cell-independent pathway. The
      coexistence of tolerance to HBc/HBe T-cell determinants and production of
      antibody to HBcAg in vivo parallels the immunologic status of neonates born to
      carrier mothers. These observations suggest that expression of HBeAg may
      represent a viral strategy to guarantee persistence after perinatal infection.
      Further studies in F1 hybrid Tg mice (B10 x B10.S-Tg31e) illustrated that "self"
      tolerance to HBeAg is variable, depending on the major histocompatibility complex
      (MHC) genotype. A proportion of T cells recognizing e129-140 in the context of I
      Ab evade induction of tolerance, persist in the periphery, and can be activated
      in vivo by a single injection of the 12 residue T-cell self-peptide. Furthermore,
      the self-reactive T cells can cooperate with self-reactive, HBeAg-specific B
      cells to mediate in vivo production of autoantibody sufficient to neutralize
      detection of the autoantigen in serum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297905
TI  - Protein and energy relationships in the broiler chicken. Effects of protein
      quantity and quality on metabolism.
AB  - Male broiler chickens growing from 7 to 35 d were fed on a diet containing 150 g
      crude protein (N x 6.25)/kg diet supplemented with lysine to equal that in diets
      containing 166, 183 and 200 g crude protein/kg diet (Expt 1). A second group of
      male broiler chickens growing over the same period were fed on a diet containing
      120 g crude protein/kg supplemented with lysine, arginine, tryptophan, threonine
      and isoleucine equal to that in diets containing 144, 172 and 200 g crude
      protein/kg diet (Expt 2). Growth was improved by lysine supplementation but not
      to the level attained by feeding 200 g crude protein/kg (Expt 1). Lysine,
      arginine, tryptophan, threonine and isoleucine supplementation of a low-protein
      diet also improved growth, but growth again fell short of that attained by
      feeding a diet containing 200 g crude protein/kg. Plasma insulin-like growth
      factor-1 and thyroxine concentrations increased and triiodothyronine decreased as
      the crude protein level increased from 150 to 200 g/kg diet. Supplemental lysine
      did not affect plasma levels of these hormones. Although dietary crude protein
      levels noticeably changed rates of in vitro lipogenesis, changing either the
      level of a single limiting amino acid or the levels of several limiting amino
      acids did not change lipogenesis.

PMID- 8297906
TI  - Effect of level of input of different proportions of volatile fatty acids on
      energy utilization in growing ruminants.
AB  - Four steers were maintained wholly by intragastric infusion of volatile fatty
      acids (VFA) and protein, together with a mineral-vitamin supplement. The infusion
      was given at three levels of energy, namely 450, 675 and 900 kJ/kg live
      weight0.75, calculated to supply energy at 1.0, 1.5 or 2.0 times that required
      for maintenance. The VFA provided 0.837 and the protein 0.163 of the energy
      infused. The molar proportions of individual VFA were varied so that the infusate
      contained 0.36-0.91 of acetic acid, 0.56-0.01 of propionic acid and a constant
      0.08 of butyric acid. Heat production was measured in respiration chambers. Urine
      was analysed for N, urea, beta-hydroxybutyrate and VFA. Blood plasma was analysed
      for beta-hydroxybutyrate, free fatty acids, insulin and glucose. As the
      proportion of acetic acid was increased, and propionic acid reduced, there was no
      change in blood or urine metabolites or in heat production until acetic acid
      exceeded a proportion of about 0.75. At higher proportions beta-hydroxybutyrate
      increased in plasma and urine, blood glucose and insulin tended to fall and
      urinary N excretion rose. At a proportion of acetic acid of > 0.80, acetate
      appeared in the urine and at > 0.86 heat production declined. The effect of level
      of infusion on the molar proportion at which plasma and urine metabolites changed
      was less clear. There was a tendency for the increase in beta-hydroxybutyrate to
      occur at a slightly lower proportion of acetic acid at the highest level of
      infusion. It is concluded that differences in heat production that are observed
      between diets are probably not caused by differences in rumen VFA
      proportions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297907
TI  - Seasonal weight loss and metabolic adaptation in rural Beninese women: the
      relationship with body mass index.
AB  - A large variation in seasonal weight loss between individuals exists in rural
      communities in developing countries. Therefore, it was investigated whether some
      individuals show a metabolic adaptation and, through that, prevent large body
      weight losses during the preharvest season. Basal metabolic rate (BMR), energy
      intake and physical activity level (PAL) of rural Beninese women were measured in
      three seasons. Groups of subjects were: women with a body mass index (BMI) < 18
      (n 18), and a BMI > 23 (n 16), and women who had shown small (n 18) and large (n
      15) preharvest weight loss. All groups of subjects decreased energy intake during
      the preharvest season by 0.66-1.09 MJ/d. PAL did not show significant seasonal
      changes in any of the four groups. Only subjects with a BMI < 18 decreased BMR
      during the preharvest season with 2.9 (SD 6.7) J/kg per min (P < 0.05), with a
      decrease of 0.8 (SD 1.4) kg (P < 0.05) in body weight. In very thin women with a
      BMI < 17 (n 5) BMR expressed per unit body weight decreased even more during the
      preharvest season (by 12%).

PMID- 8297908
TI  - A comparison of effects of body weight and feed intake on digestion in broiler
      cockerels with effects of tannins.
AB  - The effects of body size and feed intake on N digestibility, pancreas and liver
      weight, and digestive enzyme activities in male broiler chicks were compared with
      those induced by dietary tannins. Four groups (SSM, ad lib., pair-fed and young)
      of sixteen birds each (2 weeks old) were used as experimental animals. They were
      fed on experimental diets for 4 weeks, except the young group which were fed from
      age 15 d to 24 d only. Two isonitrogenous and isoenergetic diets with (SSM) or
      without salseed (Shorea robusta) meal (CONTROL) were used. SSM diet was fed ad
      lib. to SSM group and control diet was fed ad lib. to ad lib. and young birds and
      to pair-fed birds at same intake level as SSM birds. Birds fed ad lib. utilized
      their diet more efficiently than the SSM and pair-fed birds. Digestibility of N,
      both apparent and ileal, was substantially lower with SSM diet than with the
      control diet. Each of the treatments induced enlargement of the pancreas (g
      pancreas/kg live weight) when compared with ad lib. birds. There was no
      difference between the relative liver weights of SSM and ad lib. birds; however,
      pair-fed and young birds had comparatively bigger livers. In pair-fed birds the
      trypsinogen activity of pancreatic tissue (U/g pancreatic tissue) was
      significantly depressed but there was a significant elevation in trypsinogen
      (U/kg live weight) activity in SSM birds; again pair-fed birds exhibited the
      lowest value for this variable.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297909
TI  - Utilization of ileal digestible amino acids by growing pigs: methionine.
AB  - An experiment was conducted to determine the utilization of ileal digestible
      methionine by growing pigs. Three methionine-deficient diets (0.09 g ileal
      digestible methionine/MJ digestible energy (DE)) were formulated using cottonseed
      meal, meat-and-bone meal and soya-bean meal respectively as the only source of
      methionine in the diet. An additional three diets were formulated with
      supplements of methionine to confirm that methionine was limiting in the first
      three diets. The growth performance and retention of methionine by pigs given the
      six diets over the 20-45 kg growth phase was then determined. Growth rates (g/d)
      of pigs given the three diets formulated to 0.09 g ileal digestible methionine/MJ
      DE were significantly different (P < 0.01): cottonseed meal 411, meat-and-bone
      meal 442, soya-bean meal 496 (SED 24.6). The response of pigs to the addition of
      methionine confirmed that methionine was limiting in these diets. Crude protein
      (N x 6.25) deposited by the pigs (g/d) was significantly higher (P < 0.05) for
      those given soya-bean meal (61) and meat-and-bone meal (57) relative to
      cottonseed meal (47; SED 3.3). The proportion of ileal digestible methionine
      retained by pigs given the three protein concentrates was: cottonseed meal 0.39,
      meat-and-bone meal 0.45, soya-bean meal 0.47 (SED 0.019). These results indicate
      that values for the ileal digestibility of methionine in protein concentrates do
      not reflect the proportion of methionine that can be utilized by the pig. It
      appears that, with heat-processed meals, a considerable proportion of the
      methionine is absorbed in a form(s) that is (are) inefficiently utilized.

PMID- 8297910
TI  - Dietary cholesterol lowers the activity of butyrylcholinesterase (EC 3.1.1.8),
      but elevates that of esterase-1 (EC 3.1.1.1) in plasma of rats.
AB  - The question addressed is whether an increased intake of cholesterol affects
      esterase-1 (EC 3.1.1.1; ES-1) and butyrylcholinesterase (EC 3.1.1.8) activity in
      plasma. Rats were fed on a purified diet either without or with cholesterol (10
      g/kg) added at the expense of the carbohydrate source. Dietary cholesterol
      significantly decreased plasma butyrylcholinesterase activity, but raised plasma
      ES-1 activity. Evidence is discussed, suggesting that plasma
      butyrylcholinesterase is involved in plasma cholesterol metabolism, whereas
      esterase-1 is involved in intestinal cholesterol absorption.

PMID- 8297911
TI  - Pretranslational regulation of the expression of the lipoprotein lipase (EC
      3.1.1.34) gene by dietary fatty acids in the rat.
AB  - Although there have been a number of studies of effects of diet and hormones on
      lipoprotein lipase (EC 3.1.1.34; LPL) activity and levels of LPL mRNA (Raynolds
      et al. 1990), there have been no studies which have investigated effects of
      different dietary fatty acids on LPL gene expression. In the present study male
      Wistar Albino rats were pair-fed diets containing 50 g fat/kg of different fatty
      acid composition for 2 weeks. The diets fed were (1) a mixed oil (450 g saturated
      fatty acids, 420 g monounsaturated fatty acids, 130 g polyunsaturated fatty
      acids/kg; n 8), (2) maize oil (n 8), or (3) fish oil (n 8). Animals were killed,
      RNA was extracted from liver and perirenal and epididymal fat pads, and analysed
      by 'Northern methodology'. Samples were hybridized to a human cDNA probe for LPL
      (Gotoda et al. 1989). Two transcripts were identified in epididymal and perirenal
      adipose tissue which were approximately 3.7 and 1.7 kb in size. The results
      suggested that (1) fish oil-fed animals had significantly greater production of
      LPL mRNA in epididymal adipose tissue compared with maize oil-fed animals (P <
      0.05), (2) maize oil-fed animals had significantly greater production of LPL mRNA
      in perirenal fat compared with the other dietary groups (P < 0.05), (3)
      expression in the liver was not significant. Rats fed on a fish oil diet had
      significantly reduced plasma triacylglycerol concentrations compared with the
      mixed-oil group (P < 0.05), but there were no significant differences in plasma
      cholesterol. The differences in LPL could not be explained directly by the
      changes in plasma immunoreactive-insulin and glucose-dependent insulinotrophic
      polypeptide levels in the three groups.

PMID- 8297912
TI  - Inter- and intra-fat pad variation in vascularization and the release of 14C
      labelled fatty acids in mice.
AB  - Adult laca mice were dosed orally with 150 microliters whole milk containing 2.5
      microCi of either labelled stearic acid ([1-14C]18:0; n 20) or labelled linoleic
      acid ([1-14C]18:2; n 20). The mice were killed in groups of four at 6, 12, 24, 48
      and 96 h following dosing and samples of perirenal and epididymal fat pads were
      taken from both inner and outer sites at each location. Significant differences
      in the rate of loss of label between sites were found. No differences (P = 0.018)
      between fat pad locations (epididymal v. perirenal) were found. A significant
      interaction between rate of loss of labelled fatty acid and site (P = 0.019)
      reflected the fact that between-site variations in this context were confined to
      labelled linoleic acid. In a second study weanling adult (n 10) and adult (n 10)
      mice were killed and their epididymal and perirenal fat pads prepared for
      histological examination. Both transverse and longitudinal sections were taken at
      the inner and outer sites of each fat pad location. Following staining, both the
      size and number of blood vessels were measured using computer-linked microscopy.
      In all instances there were significant differences between sites with the inner
      site consistently showing greater numbers and areas of blood vessels. In general
      the number of blood vessels in the inner site tended to be greater in older mice,
      while the reverse was seen for younger mice. The results lend support to the
      concept of multiple pools of triacylglycerol-fatty acids in adipose tissue such
      that the main determinant of short-term supply of essential fatty acids is the
      quantity recently ingested.

PMID- 8297913
TI  - Ileal pH and apparent absorption of magnesium in rats fed on diets containing
      either lactose or lactulose.
AB  - The hypothesis was tested that dietary lactose v. glucose stimulates Mg
      absorption in rats because lactose lowers pH of the ileal lumen, which improves
      Mg solubility which in turn enhances Mg availability for transport across the
      ileal epithelium. For comparison, the effects of lactulose were studied because
      it shares with lactose the characteristic of being poorly digestible. Replacement
      of glucose by lactose (100 g/kg) significantly stimulated apparent absorption of
      Mg. Apart from Mg absorption, lactulose also significantly enhanced absorption of
      Ca and phosphate. Lactose v. glucose lowered the pH of the ileal lumen from 7.5
      to 7.2, whereas lactulose significantly reduced it to 7.0. In in vitro
      incubations a decrease in pH within the range of fluctuation in vivo was found to
      cause an improved solubility of Mg, and to a lesser extent also of Ca and
      phosphate. The smaller fall of ileal pH induced by feeding lactose instead of
      lactulose may explain why lactose improved Mg absorption only. For all individual
      rats combined there were negative relationships between ileal pH and apparent
      absorption of minerals, the relationship being strongest for Mg. Neither lactose
      nor lactulose was found to raise ileal solubility of minerals, which could relate
      to the possibility that the time of sampling was not appropriate. It is suggested
      that lactose-induced stimulation of Mg absorption in rats is caused by a lowering
      of ileal pH.

PMID- 8297914
TI  - Effects of oat-bran concentrate on rat serum lipids and liver fat infiltration.
AB  - Oat bran concentrated with respect to both soluble and insoluble dietary fibre
      was fed to adult rats, and its effects on serum cholesterol and liver fat
      infiltration were studied. The feeds contained 15, 30 or 45 g beta-glucan/kg,
      except in control groups where the fibre of the feed was cellulose. Half the
      experimental groups received the feeds with an addition of 10 g cholesterol and 2
      g cholic acid/kg in order to create an hypercholesterolaemic condition. In
      normocholesterolaemic rats the concentrated oat bran did not cause any
      significant changes in serum cholesterol concentrations, but reduced liver weight
      compared with control group rats fed on the cellulose-containing diet. In
      hypercholesterolaemic rats the concentrated oat bran reduced serum total
      cholesterol and increased high-density-lipoprotein cholesterol concentration. The
      effect was seen already at the 15 g/kg concentration of beta-glucan, the higher
      doses tested did not significantly improve the effect. Infiltration of fat into
      liver cells, especially in the periportal areas, was observed only in
      hypercholesterolaemic animals. The fat infiltration was accentuated in proportion
      to the amount of oat-bran concentrate fed.

PMID- 8297915
TI  - Iron status in rats fed on diets containing marginal amounts of vitamin A.
AB  - Severe vitamin A deficiency in rats is known to cause anaemia associated with
      growth retardation and impaired water retention. However, study of the effect of
      marginal vitamin A intake is of more interest because such intake may mirror the
      situation in humans in many developing countries. Therefore, in two experiments,
      the effect of marginal vitamin A deficiency on Fe status was investigated in male
      rats. After 28 d of feeding either low- or high-vitamin A diets (0 or 120 v. 1200
      retinol equivalents/kg feed), body weight and feed intake were not influenced by
      the level of vitamin A in the diet. Liver weight was lowered by vitamin A
      deficiency. Water intake was not influenced in rats fed on a low-vitamin A diet.
      Plasma retinol concentrations were decreased in rats fed on diets low in vitamin
      A. Marginal vitamin A deficiency produced slightly lower blood haemoglobin
      concentrations; it did not systematically affect packed cell volume. The
      concentration of Fe in liver was significantly higher when diets low in vitamin A
      were fed, but hepatic Fe mass was not affected. Significantly lower Fe levels
      were observed in femurs of rats with vitamin A deficiency. The effects on liver
      and femur Fe concentrations were seen with diets adequate in Fe but not with
      diets deficient in Fe. The efficiency of apparent Fe absorption was significantly
      increased by low intakes of vitamin A, provided that the dietary Fe concentration
      was adequate. It is speculated that depressed uptake of Fe by bone marrow is the
      primary feature of altered Fe status in rats with marginal vitamin A deficiency.

PMID- 8297916
TI  - Prevalence and type of anaemia in female cotton mill workers in Beijing, China.
AB  - The present study investigates the prevalence and type of anaemia in Chinese
      female cotton mill workers. The prevalence of anaemia is reported in 447 non
      pregnant female workers aged between 19 and 45 years. The mean value for
      haemoglobin (Hb) was 123 (SD 15) g/l and 150 of the total 447 subjects had Hb
      values below 120 g/l; thus 34% of the population was anaemic according to World
      Health Organization (WHO, 1975) criteria. The mean value for free erythrocyte
      protoporphyrin (FEP) was 419 (SD 215) micrograms/l; 55% of the total population
      had FEP values higher than 350 micrograms/l and 72% among the anaemic subjects.
      Serum ferritin (SF) was tested in all the women with a Hb value less than 120 g/l
      and 71% of them had SF values below 12.0 micrograms/l. Eighty women diagnosed as
      either Fe deficient or with Fe-deficient anaemia were selected for a diagnostic
      supplementation trial. They were randomly assigned to FeSO4 (60 or 120 mg Fe/d)
      or placebo treatment for 12 weeks. Fe supplementation increased mean Hb values
      from 114 to 127 g/l (P < 0.001) and SF levels from 9.7 to 30.0 micrograms/l (P <
      0.001), and decreased mean FEP values from 570 to 277 micrograms/l (P < 0.001).
      The response rate of Hb in the whole Fe-treated group or Fe-treated subjects with
      an Hb level less than 120 g/l was 90% or 92% respectively. These findings
      indicate that the type of anaemia in this population was mainly Fe deficiency. It
      was also found that in this population the severity of anaemia, not the
      prevalence, was significantly related to the use of intra-uterine devices (IUD).

PMID- 8297917
TI  - Plasma total glutathione in humans and its association with demographic and
      health-related factors.
AB  - The tripeptide glutathione is proposed to be protective against a number of
      chronic diseases including cardiovascular disease and cancer. However, there have
      been few studies of plasma glutathione levels in humans and in those studies the
      numbers of participants have been very small. In an exploratory analysis the
      determinants of plasma total glutathione (GSHt) were investigated in a group of
      100 volunteers aged 18-61 years in Atlanta, Georgia, USA during June and July
      1989. Data on demographic and health-related factors were collected by interview
      and plasma GSHt was measured using a recently modified laboratory method. The
      mean concentration of plasma GSHt for all 100 participants was 761 micrograms/l,
      with a standard deviation of 451 micrograms/l, a range of 86-2889 micrograms/l
      and a median of 649 micrograms/l. Men had significantly higher levels of plasma
      GSHt than women (924 v. 692 micrograms/l; P = 0.006). Seventh-day Adventists
      participating in the present study had higher plasma GSHt levels than other
      subgroups defined by race and/or religion. Among Seventh-day Adventists
      consumption of a vegetarian diet was associated with increased plasma GSHt
      concentration (P = 0.002). Plasma GSHt levels also appeared to vary by race, but
      relationships with race could not be clearly disassociated from relationships
      with religion. Among white participants plasma GSHt concentration decreased with
      age in women but increased with age in men (P = 0.05). Few other factors were
      associated with plasma GSHt concentration, although use of oral contraceptives (P
      = 0.10) was somewhat associated with decreased plasma GSHt levels. These findings
      suggest that plasma GSHt levels may vary with several demographic and health
      related attributes and support the need for further research on this potentially
      important disease-preventive compound.

PMID- 8297918
TI  - Xanthan gum and colonic function in man.

PMID- 8297919
TI  - McGill University, Department of Psychiatry, 50th anniversary. Part 2: Psychiatry
      in the year 2043?

PMID- 8297920
TI  - Possible use of glucocorticoid receptor antagonists in the treatment of major
      depression: preliminary results using RU 486.
AB  - The rationale for the use of anti-glucocorticoids in the treatment of major
      depression has been reviewed. Four patients with chronic severe depression who
      were resistant to conventional therapies were given RU 486 (200 mg/day) for
      periods up to eight weeks. Substantial levels of RU 486 were achieved within the
      first few days, and the levels fell gradually over the week after the treatment
      was discontinued. In three cases, treatment was stopped before the eight weeks
      were completed: in one case because of the appearance of a rash, in the others
      because of side-effects, which, in retrospect, were likely unrelated to the drug.
      The mean scores on the Hamilton Rating Scale for Depression of three patients
      decreased. Levels of adrenocorticotrophin, dehydroepiandrosterone and cortisol
      rose during treatment. These preliminary results suggest that glucocorticoid
      antagonists may be effective in the treatment of major depression and merit
      further exploration.

PMID- 8297921
TI  - Cholinergic markers in Alzheimer disease and the autoregulation of acetylcholine
      release.
AB  - The status of various cholinergic markers was compared in Alzheimer's and
      Parkinson's diseases. Rather unexpectedly, similar decrements were observed in
      choline acetyltransferase (ChAT) activity and in density of muscarinic M2 and
      nicotinic receptors in various cortical areas in these two disorders. This may
      relate to the existence of important functional interactions between cholinergic
      and dopaminergic systems in cortical and hippocampal areas. Additionally, the
      parallel decrements in nicotinic and muscarinic M2 receptor subtypes, with that
      of ChAT activities in these disorders suggest their presynaptic location. A
      series of pharmacological data do in fact reveal that nicotinic receptors may act
      as positive autoreceptors modulating basal acetylcholine release while muscarinic
      M2 receptors could act as negative autoreceptors. This information may have
      significance for the development of new treatment strategies (for example, M2
      antagonists) of disorders associated with cholinergic hypofunction.

PMID- 8297922
TI  - The use of diet and dietary components in the study of factors controlling affect
      in humans: a review.
AB  - Although one of the first biological treatments of a major psychiatric disorder
      was the dietary treatment of pellagra, the use of diet and dietary components in
      the study of psychopathology has not aroused much interest. This article reviews
      three areas in which the dietary approach has provided interesting information.
      The tryptophan depletion strategy uses a mixture of amino acids devoid of
      tryptophan to lower brain tryptophan in order to study the symptoms that can be
      elicited. One effect of tryptophan depletion is a lowering of mood, the magnitude
      of which seems to depend on the baseline state of the subject. Therefore,
      recovered depressed patients often undergo an acute relapse, while normal
      subjects show more moderate changes of mood. Totally euthymic subjects show no
      lowering of mood, but subjects with high normal depression scale scores or
      subjects with a family history of depression show a moderate lowering of mood.
      These data indicate that low serotonin levels alone cannot cause depression.
      However, serotonin does have a direct effect on mood, and low levels of serotonin
      contribute to the etiology of depression in some depressed patients. Folic acid
      deficiency causes a lowering of brain serotonin in rats, and of cerebrospinal
      fluid 5-hydroxyindoleacetic acid in humans. There is a high incidence of folate
      deficiency in depression, and there are indications in the literature that some
      depressed patients who are folate deficient respond to folate administration.
      Folate deficiency is known to lower levels of S-adenosylmethionine, and S
      adenosylmethionine is an antidepressant that raises brain serotonin levels. These
      data suggest that low levels of serotonin in some depressed patients may be a
      secondary consequence of low levels of S-adenosylmethionine. They also suggest
      that the dietary intake and psychopharmacological action of methionine, the
      precursor of S-adenosylmethionine, should be studied in patients with depression.
      Normal meals have definite effects on mood and performance in humans. The
      composition of the meal, in terms of protein and carbohydrate content, can
      influence these behaviors. Because protein and carbohydrate meals can influence
      brain serotonin in rats, these effects in humans have usually been interpreted in
      terms of altered serotonin functioning. However, the current balance of evidence
      is against the involvement of serotonin in the acute effects of protein and
      carbohydrate meals in humans. The underlying mechanisms involved are unknown, but
      there are a variety of possibilities.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8297923
TI  - Evolution of nervous systems and psychiatry: consequences of the vertical and
      horizontal duality of the evolutionary process.
AB  - Jacksonian views of brain evolution where new levels "add on" and become higher
      levels of integration "keeping down" the lower levels are examined. The
      hierarchical organization is contrasted with modern views of the evolution of
      nervous systems. These emphasize the "separation or factorization of different
      aspects of input into distinct processing channels, a factor which appears to be
      a generalized one in the evolution of brains and a necessary condition to adapt
      to a varying environment." The advantages of the latter view--vertical and
      horizontal development--for the interpretation of functional organization of
      nervous systems are discussed. The view that normal and pathological conditions
      do not form a continuum, but constitute qualitatively different phenomena, is
      presented and given support because of recent developments in neuroscience.

PMID- 8297924
TI  - Thyroid functioning during treatment for depression.
AB  - Thirty-nine unipolar depressed patients were treated, after a washout period of
      seven days in a double blind study with either moclobemide, placebo or
      amitriptyline, for 42 days. The psychopathological assessment and HRSD were done
      on seven day intervals and thyroid analysis was done on 14 day intervals. At the
      end of therapy, the levels of T4 and fT4 decreased significantly in the
      responders if amitriptyline was used, and non-significantly if placebo or
      moclobemide were used. The T4 and fT4 values of the non-responders increased non
      significantly. The weight change was minimal and non-significant.

PMID- 8297925
TI  - Delayed effects of spiperone on serotonin1A receptors in the dorsal hippocampus
      of rats.
AB  - The effects of 5-HT1A antagonists spiperone, methiothepin and BMY 7378 on [3H]-8
      OH-DPAT binding were determined in vitro and ex vivo in rat hippocampus CA3
      membrane preparations, and ex vivo in tissue sections of CA1 and CA3 subfields
      using quantitative autoradiography. In CA3 membranes from rats sacrificed 1 h or
      24 h after administration of 5 mg/kg i.p. spiperone or methiothepin, no decrease
      in [3H]-8-OH-DPAT Bmax values approached statistical significance. Autoradiograms
      from identically treated rats showed significant increases in Kd values in both
      CA1 and CA3 hippocampal subfields 24 h but not 1 h after administration of the
      drugs, while no changes were observed in the dorsal raphe at either time. In
      vitro co-incubation of membranes with spiperone (200 or 500 nM) or methiothepin
      (500 nM) resulted in significant decreases in both affinity and Bmax values. In
      contrast, co-incubation with BMY 7378 (5 nM) increased only Kd values. GTP gamma
      S produced a concentration-dependent inhibition of specific [3H]8-OH-DPAT
      binding. At 0.1 mM of GTP gamma S, Kd values were increased three-fold and Bmax
      values were significantly decreased. When membranes were co-incubated with GTP
      gamma S and spiperone or BMY 7378, Kd values increased further. Moreover, the
      effects of spiperone and GTP gamma S on Bmax values were additive. It is
      concluded that BMY 7378 acts as a competitive antagonist at hippocampal post
      synaptic 5-HT1A receptors, whereas spiperone and methiothepin exert their delayed
      antagonistic effects at these receptors through a non-competitive mechanism of
      action, possibly affecting the coupling of the receptors to their Gi/o proteins.

PMID- 8297926
TI  - Apathetic hyperthyroidism in an adolescent.

PMID- 8297927
TI  - FRAR course on laboratory approaches to aging. Mouse and rat genotype choices.
AB  - There are advantages and disadvantages to all animal models for aging research.
      Investigators need to understand these issues as well as the nature of each
      relevant model, in order to choose the best model for their research. There is no
      "best" or "worst" model for aging research. Five genetically defined rodent
      models of potential utility in aging research are: 1. Inbred strains and F1
      Hybrid mice and rats; 2. Single gene mutations and other single locus effects; 3.
      Congenic lines; 4. Recombinant Inbred (RI) strains; 5. Genetically selected
      strains and stocks. Animals of each of these types are available for research,
      but only inbred and F1 hybrid mice and rats are commercially available as aged
      animals. A general understanding of the need for careful genetic definition and
      for the best available barrier-breeding facilities has improved the quality of
      aging research significantly in the last two decades.

PMID- 8297928
TI  - FRAR course on laboratory approaches to aging. The role of pathology in rodent
      experimental gerontology.
AB  - The distinction between aging and age-related disease is a blurred one at best.
      Pathologic lesions and diseases, while having obvious importance for the well
      being of an individual, are not more indicative of aging than are silent or
      benign aging changes. All lesions are useful as biomarkers of aging. They are
      definable, and can be characterized in terms of their prevalence and severity in
      different species, genotypes, genders, and age groups. Some data from previous
      studies are presented as examples. Many lesions of aging are quite restricted, in
      terms of prevalence or severity, to specific genotypes, species or genders.
      Recognition of the very great diversity of lesion biomarkers between genotypes,
      genders and species should prevent investigators from extrapolating findings in
      one genotype-gender to any other.

PMID- 8297929
TI  - FRAR course on laboratory approaches to aging. The comparative perspective and
      choice of animal models in aging research.
AB  - The comparative perspective may be defined as the assumption that individual
      species or populations differ from one another in potentially instructive ways,
      and that an appropriate analysis of the nature and magnitude of these differences
      will yield insights into fundamental processes of aging. Modern experimental
      research on aging has largely lost its comparative focus, and virtually all
      research on mammals utilizes inbred strains of laboratory rats and mice, two
      closely related species chosen not for their properties vis a vis aging, but for
      convenience. In fact, from a mammalian life history perspective, humans are at
      the opposite end of the aging continuum than these animal models and other small
      species conducive to laboratory research, mimic human life history much better.
      The comparative perspective may play four roles in aging research: 1) hypothesis
      formulation and evaluation; 2) assessing the generality of aging mechanisms,
      typically requiring a choice of several animal models distantly related to one
      another; 3) isolation of key factors influencing aging rate, requiring model
      systems as closely-related to one another as possible, but differing with respect
      to aging rate (intraspecific variation in aging rate is particularly useful
      here); 4) choosing of animal models with particular properties in mind, such as
      the spectacularly effective antioxidant systems of bats. Increasing the range of
      animal models used in aging research will accelerate progress in understanding
      and perhaps manipulating human aging.

PMID- 8297930
TI  - FRAR course on laboratory approaches to aging. Nutrition, including diet
      restriction, in mammals.
AB  - Although diet influences basic aging processes as well as age-associated disease
      processes, diet is either not mentioned or inadequately described in reports of
      gerontologic studies using animal models. Studies carried out in our laboratory
      with male F344 rats are a good example of the importance of diet in the use of an
      animal model for aging research. Nephropathy, resulting in kidney failure, is
      often an overwhelming disease problem in life span studies using ad libitum fed
      male F344 rats. However, by appropriate choice of dietary components, nephropathy
      can be reduced to only one of several disease processes contributing to the death
      of these ad libitum fed rats. Such diets greatly increase the value of the male
      F344 rat as a model for aging research. Because almost all rodent species and
      strains suffer from one or more major age-associated diseases, nutritional
      conditions should be sought in the case of each to minimize the occurrence of
      such diseases during an aging study. Restriction of energy intake (often called
      food restriction or dietary restriction) delays or prevents most age-associated
      disease processes in a spectrum of rat and mouse strains. It is, therefore,
      suggested that the dietary restricted rodent be used as the standard or base
      model for aging research. Moreover, dietary restriction is proving to be a
      powerful tool for the study of aging processes.

PMID- 8297931
TI  - FRAR course on laboratory approaches to aging. Theories of aging.
AB  - This review of gerontological theory cites diverse examples of neural and
      endocrine involvement in the senescence of mammals and some other multicellular
      species that suggest fundamental involvement in age-related changes in cell
      functions. The data support the major hypothesis that age-related changes are
      generally caused by specific physiological factors that are extrinsic to cells.
      The success of these manipulations includes retarding or reversing specific age
      related changes, and extending the life span. From another perspective, these
      findings have converted time in the analysis of senescence from an independent
      variable to a dependent variable. So far, we do not need to hypothesize any new
      mechanism that is not already known in disease or normal functioning.

PMID- 8297932
TI  - FRAR course on laboratory approaches to aging. Cellular aging, in vitro and in
      vivo.
AB  - Human cells grown in culture exhibit exponential growth provided they are
      regularly provided with fresh medium. This exponential growth is limited, and
      although the cells eventually cease to divide, they remain viable for long
      periods of time. Such a culture is deemed to be "senescent", but it is not clear
      whether this reflects the growth pattern of cells in vivo. Considerable evidence
      has been obtained to correlate cell senescence in vitro with aging in vivo, but
      there is no convincing evidence that any organ or tissue ages as a result of
      senescence of its individual cells. Recently gained insights into the control of
      cell proliferation through studies of cell senescence, and the relevance of cell
      senescence as a strategy to prevent carcinogenesis are of particular interest.

PMID- 8297933
TI  - FRAR course on laboratory approaches to aging. Genetic influences on aging in
      mammals and invertebrates.
AB  - A central theme underlies this review: "Genetics offers an important tool for
      identifying key molecular events that are involved in specifying biological
      functions." This approach has been used repeatedly to understand such diverse
      biological phenomena as oncogenesis, development, and the cell cycle, but has
      only recently been applied to the analysis of organismic aging and senescence.
      The power of the genetic approach lies in the ability to integrate phenomena that
      are displayed at multiple observational levels (i.e., from the molecular to the
      whole organism), and the power to reveal causal factors that are not dependent
      upon the prejudice of the investigator. I discuss several areas where genetics
      has been fruitfully applied to the study of the aging processes: human genes
      identified by "segmental progeroid" mutations; neurological diseases of the
      elderly; the limited proliferative life span of human somatic cells in tissue
      culture; studies on the life span of the mouse; and genetic analysis of life span
      in shorter-lived metazoans (Drosophila melanogaster and Caenorhabditis elegans),
      and the yeast Saccharomyces cerevisiae.

PMID- 8297934
TI  - FRAR course on laboratory approaches to aging. Genetic quality control in
      laboratory rodents.
AB  - Laboratory rodents are widely used in gerontological research. Many different
      strains are available, and superficially there is little to distinguish them
      (many are albino), although they may differ markedly in life span and pattern of
      spontaneous disease, as well as for a whole range of biochemical, immunological,
      behavioural and physiological characteristics. As experience has shown that
      strains can easily become muddled, some form of genetic quality control is
      essential. There is no single method of genetic quality control which can be
      recommended for all occasions. Methods based on identification of Mendelian
      genetic markers, such as biochemical and immunological polymorphisms can be
      sensitive, but may be expensive and require considerable expertise. Methods based
      on simultaneous study of several markers, such as skin grafting and polyvalent
      strain-specific antisera, may be cheaper but less flexible. DNA fingerprinting
      and the use of microsatellite markers appear to be the methods of choice in the
      future, though these are still expensive and require considerable expertise.

PMID- 8297935
TI  - FRAR course on laboratory approaches to aging. Microbiological effects and
      quality control in laboratory rodents.
AB  - Numerous viruses, mycoplasmas, bacteria and parasites have been associated with
      infectious diseases in laboratory animals. It is clear that pathogenic agents
      causing overt disease represent a serious hazard to research results in both
      short- as well as long-term studies. However, these organisms may contaminate
      colonies without causing any clinical or pathological symptom. This makes
      research less reliable because of the more subtle effects of the silent
      infections, especially in long-term studies as in aging research. The
      establishment of animal colonies that were free from these (micro-) organisms has
      increased substantially the value of animals used in biomedical research.
      Characterization of the health status and microbiological monitoring of the
      animals in experiments are particularly important. This paper reviews many of the
      major considerations in the efforts to maintain animals free of unwanted
      organisms, including quality and sources of animals, transportation and
      quarantine, maintenance during experimentation, microbiological characterization
      and monitoring of animals and environment.

PMID- 8297936
TI  - FRAR course on laboratory approaches to aging. "Orphan" phenotypes in
      gerontological research.
AB  - It is argued that, in addition to investigations of life span parameters, a large
      number of biomedically important phenotypes can be profitably studied from a
      gerontological perspective. These would include "private" patterns of aging,
      especially in our own species, which exhibits extraordinary genetic
      heterogeneity. These, as well as a number of relatively common age-associated
      phenotypes, have been comparatively neglected by the gerontological community,
      and therefore warrant the designation as "orphan" phenotypes. From a tabulation
      of examples from each of the major body systems, five are elaborated upon:
      "hyperhippocampals," defined as individuals with intrinsically enhanced
      functional reserve in relevant neural circuitry; patients with a heterogeneous
      set of pathologies collectively referred to as "normal pressure hydrocephalus";
      patients with late life activation of herpes zoster; individuals with unusually
      early onset of loss of olfactory function; and geriatric subjects with unusual
      sensitivity to "jet lag."

PMID- 8297937
TI  - Pitfalls of body fat assessments in premature infants by anthropometry.
AB  - Subcutaneous fat mass (SFM) and total fat mass (TFM) were estimated in 16 preterm
      infants at 8 +/- 2 days postnatal age. SFM was estimated from anthropometric
      measurements: 5 skinfold thicknesses, 5 body circumferences, and regional body
      lengths. TFM was estimated from total body water measurements using dilution of
      isotopic water, H2(18)O. The proportion of TFM that was SFM decreased with an
      increase in TFM. In infants with less than 100 g of TFM (5% body weight), 74% of
      TFM is in the subcutaneous layer compared with only 35% in infants with higher
      TFM (more than 100 g). Subscapular skinfold thickness is the best predictor of
      TFM (r = 0.78). Additional skinfold thickness measurements (triceps, biceps,
      supra-iliac and thigh) do not improve the predictability of TFM by the
      subscapular skinfold thickness. We conclude that measurement of subscapular
      skinfold thickness is an appropriate choice for estimating fat deposition in
      preterm infants, particularly in field studies and in developing countries.

PMID- 8297938
TI  - Effects of a continuous infusion of tris(hydroxymethyl)aminomethane on acidosis,
      oxygen affinity, and serum osmolality.
AB  - The effects of a continuous infusion of tris(hydroxymethyl)aminomethane (THAM) on
      pH, base excess, p50, serum osmolality, and plasma drug concentration during
      respiratory acidosis were studied in newborn piglets. Measurements were made
      during three experimental periods: (1) control period with normal blood gases;
      (2) hypercapnia period, and (3) hypercapnia plus THAM period (THAM infusion: 1.65
      mmol/kg/h). pH decreased and paCO2 increased between control period (7.40 +/-
      0.05 and 45 +/- 3 mm Hg) and hypercapnia period (7.24 +/- 0.06 and 59 +/- 2 mm
      Hg; p < 0.001; mean +/- SD). pH returned to baseline (7.37 +/- 0.04) during the
      hypercapnia plus THAM period, while paCO2 remained elevated (63 +/- 4 mm Hg). p50
      increased from 30.7 +/- 5.9 to 38.3 +/- 4.7 (p < 0.05) during hypercapnia and
      decreased with hypercapnia plus THAM. THAM concentration and base excess
      increased with time and were linearly related. Serum osmolality was unchanged
      during the THAM infusion. We conclude that continuous infusion of THAM is
      effective in normalizing pH during respiratory acidosis in the piglet.

PMID- 8297939
TI  - Lipoprotein lipase in developing rat tissues: differences between Wistar and
      Sprague-Dawley rats.
AB  - Lipoprotein lipase in animal tissues is known to be affected by fasting, but
      contradictory results have been published concerning this effect in particular
      tissues. For example, we reported that lipoprotein lipase activity expressed in
      the liver of neonatal rats was either increased or not affected by fasting. To
      evaluate the influence of the rat strain used as experimental animal model, we
      studied differences between Wistar and Sprague-Dawley rats in the development and
      in the effect of fasting on lipoprotein lipase and hepatic lipase activities in
      tissues of neonatal rats. Beside some minor differences in the development of
      lipoprotein lipase in some tissues like brown adipose tissue and lungs, we found
      quite remarkable differences between both strains in the development of
      lipoprotein lipase and hepatic lipase activities in the liver. In 1-day-old
      neonates, differences between both strains were also observed in the effect of
      fasting on lipoprotein lipase activity both in liver and lungs. In the liver of
      Wistar pups lipoprotein lipase activity was increased by fasting by 350%, but
      only by 50% in the liver of Sprague-Dawley pups. In contrast, in the lungs of
      Wistar pups lipoprotein lipase activity was increased by fasting by 280%, but by
      580% in lungs of Sprague-Dawley rats. Therefore, our results indicate that
      quantitative differences exist between Wistar and Sprague-Dawley rats in the
      regulation of lipoprotein lipase.

PMID- 8297940
TI  - Effect of maternal hyperglycemia on NaK ATPase activity in fetal rat kidney.
AB  - The effect of moderate hyperglycemia on renal ATP production and ATPase activity
      of rat fetus was investigated using the experimental procedure of maternal
      continuous infusion of glucose during the last 5 days of gestation. Glucose
      infused mothers and their fetuses showed a high level of glycemia (8.8 and 5.5
      mM, respectively) and a high level of insulinemia (3 times higher than in
      controls). No change in either ATP or ADP concentration was detectable but an
      increase in NaK ATPase activity occurred without any change in Mg ATPase
      activity. These modifications should be the result of an enhanced Na/glucose
      cotransport leading to an enhanced extrusion of Na at the basolateral membrane.
      These results indicate that immature kidney is able to increase NaK ATPase
      activity to maintain Na homeostasis.

PMID- 8297941
TI  - Postnatal changes in receptor-mediated rabbit gastric smooth muscle relaxation.
AB  - The aims of this study were to identify mediators of relaxation in rabbit
      proximal gastric circular smooth muscle and to assess age-dependent changes in
      tissue response. Vasoactive intestinal peptide (VIP), adenosine, and
      norepinephrine induced tetrodotoxin-insensitive, concentration-dependent
      relaxation in bethanechol-precontracted (3 microM) gastric muscle strips from
      newborns and weanlings. Maximally effective concentrations of 10 microM VIP
      induced complete relaxation in newborns, but only 30% relaxation in weanlings (p
      < 0.01). Maximally effective concentrations of adenosine induced complete
      relaxation at both ages. Adenosine (ED50 3 microM) was more potent than adenosine
      triphosphate, indicating the presence of P1 purinergic receptors. In newborns
      norepinephrine induced complete relaxation (ED50 0.5 microM). The response to
      norepinephrine changed in age-dependent increments from relaxation in newborns to
      strong contraction in weanlings. In weanlings phentolamine inhibited
      norepinephrine-stimulated contraction, revealing persistent propranolol-sensitive
      relaxation. Tetrodotoxin and atropine had no effect on norepinephrine-stimulated
      contraction. In summary, in rabbit gastric circular smooth muscle: (1) VIP,
      adenosine, and norepinephrine induce relaxation; (2) VIP loses efficacy with age;
      (3) there is a beta-adrenergic receptor mediating relaxation in the newborn which
      persists, and (4) an alpha-adrenergic receptor mediating contraction emerges
      early in postnatal life. Age-dependent changes in response to VIP and
      norepinephrine may contribute to the postnatal maturation of the gastric
      motility.

PMID- 8297942
TI  - Reversal of lung maturational delay in the fetus of the diabetic rat using
      triiodothyronine or dexamethasone.
AB  - Administration of glucocorticoids and thyroid hormone can accelerate fetal lung
      development. To investigate whether the delayed fetal lung maturation seen in the
      diabetic rat gestation could be reversed by dexamethasone (DEX) or
      triiodothyronine (T3), control and streptozotocin-diabetic dams were injected
      daily from day 18 of gestation with either saline, 0.5 mg/kg DEX, or 1 mg/kg T3
      until sacrifice on day 21 or day 22. While DEX did not change glucose levels in
      diabetic animals, T3 resulted in a slight reduction in both maternal (474 +/- 25
      vs. 539 +/- 17 mg%; p < 0.07) and fetal (354 +/- 43 vs. 404 +/- 26 mg%; p < 0.05)
      serum glucose concentrations. DEX therapy exaggerated the reduction in body and
      lung weight seen in fetuses of streptozotocin-diabetic dams. Fetal lung
      phosphatidylcholine and disaturated phosphatidylcholine levels were significantly
      reduced in saline-treated diabetic animals as compared with controls. However,
      fetuses of T3- or DEX-treated diabetic rats had significantly increased lung
      phosphatidylcholine and disaturated phosphatidylcholine levels were significantly
      reduced in saline-treated diabetic animals as compared with controls. However,
      fetuses of T3- or DEX-treated diabetic rats had significantly increased lung
      phosphatidylcholine and disaturated phosphatidylcholine levels as compared with
      fetuses of untreated diabetic rats; these data suggest that maternal DEX or T3
      therapy reverses the delayed fetal lung maturation seen in the diabetic rat
      gestation. Since glucocorticoids can exacerbate maternal diabetes, treatment with
      thyroid hormone may be more appropriate, although risks must be weighed against
      potential benefits.

PMID- 8297943
TI  - Thoracic duct lymph flow in fetal sheep with increased venous pressure from
      electrically induced tachycardia.
AB  - The intent of this study was to investigate thoracic duct lymph flow, as it is
      related to the development of hydrops fetalis during rapid atrial pacing. We
      studied 6 fetal sheep at 128 +/- 6 days of gestation who had chronically placed
      thoracic duct catheters, aortic and superior vena cava catheters, and atrial
      pacing electrodes. Atrial pacing at 317 beats/min caused an elevation in central
      venous pressure from a baseline value of 3 Torr to 7 Torr without affecting pH,
      arterial blood gas tensions, aortic blood pressure, total protein concentration,
      or colloid osmotic pressure, although there was a small rise in hematocrit. The
      thoracic duct lymph flow rate at baseline was 41 +/- 6 ml/h. After atrial pacing
      for 6 h, the lymph flow rate as measured over at least three consecutive 10-min
      intervals, and presumably the transvascular fluid filtration rate, increased to
      67 +/- 7 ml/h if it was collected at an outflow pressure of 3 Torr, equal to the
      venous pressure prior to the onset of atrial pacing. However, if the lymph was
      collected instead at an outflow pressure of 7 Torr, equal to the actual venous
      pressure measured with rapid atrial pacing, then the lymph flow rate diminished
      to 48 +/- 5 ml/h. This difference in lymph flow secondary to the increase in
      venous pressure could account for a maximum of 19 ml/h of edema that accumulates
      in fetal interstitium and body cavities with atrial pacing.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8297944
TI  - [Anesthesia in thoracic surgery].

PMID- 8297945
TI  - [Infections caused by intravascular catheters. Etiopathogenesis--diagnosis-
      therapy--prevention].
AB  - Despite improvements in infection control measures, catheter-related infections
      represent a challenging problem in modern medicine. The difficulties in correctly
      diagnosing catheter-related infections and the necessity to remove the device in
      case of suspected infection require preventive measures in the first place. Most
      authors stress the importance of strict aseptic catheter management.
      Nevertheless, there may still be a high incidence of catheter-related infections.
      Moreover, this problem is potentiated by the increasing use of intravascular
      devices. The current infection rates may be reduced by instituting novel
      preventive measures, e.g., decontamination of carriers using the anti
      staphylococcal agent mupirocin. Another approach aims at inhibiting the adhesion
      of bacteria to intravascular catheters by modifying these catheters with
      antimicrobial agents. Newer studies show that impregnation of catheters with the
      antiseptic substances silver-sulphadiazine and chlorhexidine is effective in
      reducing bacterial colonisation of the catheters. A pilot study on intensive-care
      patients demonstrated a significant reduction in catheter-related infections and
      bacteraemia by impregnated catheters. This novel approach may reduce the
      incidence of catheter-related infections below the level which could be achieved
      by employing all current preventive measures.

PMID- 8297946
TI  - [Comparative effectiveness and tolerance study of a new galenic etomidate
      formula].
AB  - OBJECTIVE AND STUDY DESIGN: One of the major disadvantages of etomidate is the
      high frequency of pain on injection. A new galenic formulation based on a lipid
      emulsion for etomidate (Etomidat-Lipuro) was compared with the commercial
      standard (etomidate in propylene glycol, Hypnomidate) in a prospective,
      randomised, double-blind clinical evaluation in 232 patients undergoing elective
      surgery in general anaesthesia. The patients were premedicated with flunitrazepam
      2 hours before the investigation. Two intravenous cannulas were inserted in veins
      of forearm or back of the hand. One cannula was only used for the application of
      etomidate and removed immediately after injection. General anaesthesia was
      induced with 0.3 mg/kg etomidate at an injection rate of 20 mg/30 s. If the
      patient did not complain of pain or other sensations during injection
      spontaneously, he was questioned for 15 s after beginning of injection. The arm
      used for application of etomidate was kept free of any manipulation during the
      operation and the following five postoperative days. RESULTS: There were marked
      differences between the two etomidate preparations concerning venous irritation.
      About 20% of the patients receiving the hypnotic in propylene glycol complained
      spontaneously of pain on injection, whereas none with the lipid emulsion. No
      difference was found in the incidence of myoclonic movements. The time interval
      between the beginning of injection and loss of eyelid closure reflex was about 50
      s and not different for the two galenic formulations. Blood pressure during and
      after induction of anaesthesia did not differ. The heart rate in the group of
      patients with etomidate in lipid emulsion was slightly increased before and
      immediately after intubation compared to the propylene glycol group. 4% of the
      patients in the propylene glycol group suffered from postoperative venous
      complications as reddening, swelling, induration or pain. These complications
      could not be seen in the lipid emulsion group.

PMID- 8297947
TI  - [Neurolytic block of the lumbar sympathetic trunk in advanced stages of
      peripheral arterial occlusive disease].
AB  - Neurolytic blocks of the lumbar sympathetic trunk enable a less invasive
      sympathetic denervation if compared to standard surgical procedures. METHODS: 34
      patients undergoing chemical lumbar sympathectomy (CLS) for advanced arterial
      occlusive disease were prospectively studied. An actual indication for
      reconstructive vascular surgical intervention had been excluded in all patients.
      The sympatholytic efficacy, different haemodynamic variables, the relief of rest
      pain and the effect on ischaemic ulcers were quantified before, 3 and 21 days
      after CLS. RESULTS: The mean intensity of rest pain, as assessed on a visual
      analogue scale (0-100 mm), significantly decreased from 60 mm to 31 and 34 mm,
      respectively. 9 of 12 patients with ischaemic ulcers showed partial or complete
      remission within the study period. Overall, in 88% of patients sympathetic
      denervation could be demonstrated by ablation of the sympatho-galvanic skin
      response. The mean difference in skin temperature between the treated and the
      untreated leg significantly increased from -0.73 degrees C to +0.34 and +0.39
      degrees C, respectively. Doppler-sonographic measurements of the ankle-pressure
      index showed a minor increase from 0.34 to 0.36 and 0.42; however, these changes
      did not reach significance. Neither changes of the different physiologic
      variables nor data of the patient history could predict the relief of rest pain
      after CLS. The only side effect of CLS was transient neuralgia of the
      genitofemoral nerve occurring in 19% of patients. CONCLUSION: Considering the
      relatively short follow-up period, the results of this study support evidence of
      the therapeutic efficacy of CLS for rest pain and ischaemic ulcers in patients
      with advanced arterial disease. The prognostic value of standard variables for
      estimation of sympathetic reactivity and skin blood flow, however, could not be
      confirmed.

PMID- 8297948
TI  - [High purity ryanodine for in vitro diagnosis of malignant hyperthermia].
AB  - OBJECTIVE AND STUDY DESIGN: The identification of disposition for malignant
      hyperthermia (MH) is performed by the halothane-caffeine contracture test in
      skeletal muscle. However, testing currently renders about 14% of the patients MH
      equivocal (MHE). To reduce this number the "ryanodine contracture test" has been
      proposed in addition to the established procedure. As all ryanodine preparations
      used until now are combinations of ryanodine and dehydroryanodine, we investigate
      in this study the effects of the now available high-purity ryanodine (HPR) in
      concentrations of 2,5 and 10 mumol/l. RESULTS: With all concentrations
      contractures appeared significantly earlier in MHS (malignant hyperthermia
      susceptible) than in MHN (malignant hyperthermia non-susceptible). However, only
      at 2 mumol/l a time overlap between both groups was not observed. By defining a
      time interval for MHS and MHN, three of the MHE patients could be assigned to MHS
      and three to MHN following their ryanodine-induced contractures. CONCLUSION: The
      ryanodine contracture test should be added to the current diagnostics of
      malignant hyperthermia.

PMID- 8297949
TI  - [Anesthesia in thoracic surgery].

PMID- 8297950
TI  - [Preoperative functional diagnosis in thoracic surgery interventions].

PMID- 8297951
TI  - [Thoracic surgery and the anesthetist].

PMID- 8297953
TI  - [Hypoxic pulmonary vasoconstriction].

PMID- 8297952
TI  - [Ventilation techniques in thoracic surgery].

PMID- 8297954
TI  - [Antimycotic therapy on intensive care units: contra].

PMID- 8297955
TI  - [Antimycotic therapy on intensive care units: pro].

PMID- 8297956
TI  - [Heinrich Braun (1862-1934)--a pioneer in anesthesiology in Germany].
AB  - Heinrich Braun was born on January, 1, 1862. He attended school in Dresden and
      was a student of Medicine at the Universities of Strassburg, Greifswald and
      Leipzig between 1881 and 1887. In 1887 he acquired his doctorate degree. Von
      Volkmann was his teacher in surgery in Halle. From 1891 to 1905 he worked in
      different non-university hospitals in Leipzig. In 1894 he was promoted "doctor
      habilitatus" under Thiersch as an extern. He lectured on general and local
      anaesthesia as a "Privatdozent". In 1905 he was appointed extraordinary Professor
      at the Medical Faculty of the University of Leipzig. 1906 he left Leipzig and
      became Chief Surgeon and Medical Director of the Royal Saxonian Hospital in
      Zwickau. In this position he worked until his retirement in 1928. He died on
      April, 26, 1934 in Uberlingen. Heinrich Braun's contributions to the development
      of anaesthesiology are numerous. They concern general as well as local and
      regional anaesthesia. In 1901 he designed an apparatus for mixed-gas anaesthesia
      and reported on experiences with combined inhalational anaesthesia with ether and
      chloroform. In 1903 he recommended on the basis of profound experimental
      investigations to add adrenalin as a vasoconstrictor to local anaesthetics. In
      1905 the first edition of his manual "Local Anaesthesia--Scientific Basis and
      Medical Practice" appeared. Braun extended the general practice of local and
      regional anaesthesia significantly. Famous representatives of his school are
      Lawen, Peuckert, Kulenkampff, Hartel and Kappis. In Zwickau he extensively dealt
      with problems of hospital organisation and -construction. In 1921 the new
      "Krankenstift Zwickau" constructed on the basis of his plans and recommendations
      was inaugurated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8297957
TI  - [Connector for double-lumen tubes in thoracic surgery interventions].
AB  - The junction between double-lumen endotracheal tube (DLT) and anaesthetic circuit
      is of crucial importance to modern anaesthesiological management in thoracic
      surgery. We present a connector which allows for all the essential procedures,
      such as clinical control of DLT position, use of fiberoptic bronchoscope (FOB) to
      control or correct DLT position, application of differential lung ventilation
      patterns or simple suction manoeuvres by easy handling, minimal interference, and
      avoidance of disconnection or clamping.

PMID- 8297958
TI  - A longitudinal microbiological study on osseointegrated titanium implants in
      partially edentulous patients.
AB  - The aim was to longitudinally follow the colonization of putative periodontal
      pathogens on titanium implants in partially edentulous patients. Nineteen
      individuals, who were partially edentulous and were on the waiting-list to be
      treated with titanium fixtures, were included in the study. They were treated for
      periodontal disease with oral hygiene instructions and supra- and subgingival
      debridement and were left for maintenance. Full-mouth recordings of each patient
      were performed at baseline, including attachment level and probing pocket depth.
      Bleeding was provoked and visible plaque were registered. Subgingival samples
      were taken for examination of Porphyromonas gingivalis, Prevotella intermedia and
      Actinobacillus actinomycetemcomitans. Bridge connection was completed 1 month
      after abutment connection. The bone level was registered on radiographs. The
      patients were followed with clinical registrations and subgingival samples at 6,
      12, 24 and 36 months. No significant changes in pocket depth, attachment level,
      bleeding on probing or plaque score occurred during the experimental period. The
      number of individuals positive at teeth and abutments for the various bacterial
      species reached approximately similar levels at 6 months. No significant changes
      over time were seen. Comparison between bone height, seen on radiographs, at
      abutments after 2, 12 and 36 months gave only 3 sites with bone loss of > 0.5 mm.
      All these sites were found in one patient and were accompanied by P. intermedia.

PMID- 8297959
TI  - The role of early versus late removal of GTAM membranes on bone formation at oral
      implants placed into immediate extraction sockets. An experimental study in dogs.
AB  - The purpose of this study was to compare the effect of early versus late removal
      of expanded polytetrafluoroethylene (e-PTFE) membranes on bone formation at oral
      implants. Thirty Branemark fixtures were placed into immediate extraction sockets
      with buccal bone dehiscences augmented by e-PTFE membranes. At 4 weeks, the
      membranes and underlying soft tissues were removed from 5 implants, but at 16
      sites only the membranes were extirpated. In 9 sites, the membranes remained in
      place during the healing period. Sixteen weeks after fixture insertion, the sites
      in which the membrane was retained (MRET) showed an average of 5.2 mm of clinical
      bone height increase (100% of bone fill). For sites where the membrane together
      with underlying soft tissues were removed (MRB), the corresponding value was 2.0
      mm (42% of bone fill). Implants at which only the membrane was removed (MR)
      showed the least clinical bone height increase (1.0 mm), resulting in 21%
      coverage of original threads. Histometric measurements verified that the MRET
      sites had the least distance from the top of the fixture to the newly formed bone
      level (0.4 mm). However, in contrast with the clinical findings, the histometric
      analyses showed that the MRB group had the greatest remaining bone defect (3.3
      mm). The clinical and histometric results of the MRET group were statistically
      better, though, compared with those of the other two groups. Biopsies, removed
      from beneath the membranes, revealed slightly inflamed connective tissue,
      containing spicules of newly formed bone, indicating that more bone might have
      been created if the membranes had been retained longer.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8297960
TI  - New periodontal ligament formation on a synthetic hydroxyapatite surface.
AB  - The aim of this study was to investigate whether a new connective tissue
      attachment can occur on a surface of hydroxyapatite (HA) when periodontal
      ligament (PDL)-derived cells with the ability to form new connective tissue
      attachment are allowed to populate the surface of HA. Six maxillary canines from
      3 cats were used for this experiment. Under anesthesia, fenestration of the
      buccal alveolar bone was performed over the canine root and a cavity was prepared
      on the root surface. A synthetic HA block was inlaid and cemented into the root
      cavity. A Teflon membrane was then placed to cover the access opening of the
      alveolar bone to guide PDL-derived cell proliferation into the surface of the HA
      block. Finally, the gingival tissue flap was replaced and sutured. Six months
      after the operation, histologic evaluation was done by serial sections. In 4 of
      the 6 canines, PDL-derived cells successfully populated the HA surfaces and a
      layer of cementum-like tissue was formed on the HA blocks. A PDL-like connective
      tissue layer was seen between the cementum-like layer covering the exposed HA
      surface and the newly formed alveolar bone sealing the bone fenestration.
      Collagen fibers in the PDL-like tissue inserted their ends into the newly formed
      bone and the cementum-like tissue. The present findings demonstrated that PDL
      derived cells can form a new connective tissue attachment on HA.

PMID- 8297961
TI  - Glycosaminoglycans in peri-implant sulcus fluid from implants supporting fixed or
      removable prostheses.
AB  - Previous studies have indicated that examination of glycosaminoglycans (GAG)
      present in peri-implant sulcus fluid (PISF) may be a useful indicator of
      metabolic activity of the supporting bone. The GAG content in PISF from
      osseointegrated implants ad modum Branemark in the maxilla was quantified and
      analysed. The study comprised 2 groups with 10 patients in each group. In one
      group the patients wore removable prostheses; in group 2 the patients wore fixed
      prostheses. The groups were matched for age, sex and function period of their
      prosthetic appliances. Clinical data were recorded, and the levels of the GAG
      hyaluronan (HA) and chondroitin-4-sulphate (C4S) were assessed using cellulose
      acetate electrophoresis and densitometric scanning of Alcian blue-stained strips
      against known GAG standards. PISF volumes and levels of C4S as potential bone
      marker showed no significant difference (both groups median 0.003 microgram).
      There was a somewhat higher median value for HA (0.015 microgram) in the group of
      patients with removable prostheses compared with the group with fixed prosthesis
      (HA = 0.008 micrograms) (NS). HA is known to be present in high amounts in
      gingival tissue. As both plaque index and gingival bleeding were more frequent in
      patients with removable prostheses, this may be the reason for the somewhat
      higher value for HA in this group of patients. The difference in biomechanical
      properties of fixed and removable prostheses on implants do not appear to be
      reflected in the bone responses as measured by GAG content in PISF.

PMID- 8297962
TI  - The surface analysis of implant materials. 1. The surface composition of a
      titanium dental implant material.
AB  - The surfaces of titanium (Ti) plates, as models for Ti implants, have been
      characterized by X-ray photoelectron spectroscopy (XPS) and time-of-flight
      secondary ion mass spectrometry (TOF SIMS). Plates were prepared with rough and
      smooth surface topographies--the rough being similar to that of an implant. The
      XPS data has been used to construct a model of the plates' surface chemical
      structure, from the gas-solid interface through to pure Ti metal. At the surface
      of as-received plates, which underwent the same preparative procedure as an
      implant, considerable surface contamination was detected. In particular, high
      levels of carbon (C) contaminants were detected; the nature of this C was
      elucidated by fitting the C 1s core line and from the secondary ion mass spectra.
      The oxygen (O) 1s core line could not be fitted using a minimum of 2 gaussian
      peaks, demonstrating the multiplicity of O environments. The detection of other
      elements in the XPS analysis further demonstrated that, in nominally pure Ti
      plates, the surface chemical composition deviates considerably from that of the
      bulk. The data obtained from the plates were confirmed by examination of a Ti
      abutment. The handling of Ti plates with stainless steel tweezers was
      investigated. No obvious change in surface chemistry was detected. All the above
      results bring into serious questions the validity of rigorous protocols demanded,
      in some techniques, in the handling and use of Ti implants.

PMID- 8297963
TI  - Radiological evaluation of marginal bone loss at tooth surfaces facing single
      Branemark implants.
AB  - A radiologic evaluation of marginal bone loss around single implants ad modum
      Branemark and their adjacent teeth was performed: 58 adults with 71 fixtures were
      followed up to 3 years after crown installation. The following factors were
      considered: age, cause of tooth loss, vertical relation between fixture and
      teeth, distance between adjacent teeth, distance between fixture and natural
      tooth, jaw region. Specified distance were measured as well as marginal bone
      levels around fixtures and tooth surfaces in magnified standardized intraoral
      radiographs. The results show a loss of marginal bone support at tooth surfaces
      adjacent to inserted implants during the interval between preoperative
      examination and crown installation that exceeds the loss during subsequent years.
      The largest bone loss was observed when implants were placed next to lateral
      upper incisors. A strong correlation was found between bone loss at adjacent
      teeth and the horizontal distance fixture-tooth. With decreasing distance the
      bone loss increased, especially in the upper incisor region. At present it seems
      difficult to predict which individual or individual condition may have a higher
      risk for bone loss, due to large intra- and interindividual variation.

PMID- 8297964
TI  - Bacterial colonization of the internal part of two-stage implants. An in vivo
      study.
AB  - This study aimed to investigate the presence of microorganisms in the inner
      thread of the fixture (endosteal implant part) of the Branemark system. In 9
      volunteers the apical part of 2 abutment screws that had been in place for 3
      months was examined by means of differential phase-contrast microscopy. All
      screws harboured a significant quantity of microorganisms, mainly coccoid cells
      (86.2%) and nonmotile rods (12.3%). Motile organisms (1.3%) or spirochetes (0.1%)
      were only sporadically registered. A microbial leakage at the abutment/fixture
      interface probably is the most probable origin for this contamination.

PMID- 8297965
TI  - [Clinical epidemiological studies: the translation of their results into clinical
      practice].

PMID- 8297966
TI  - [Health surveys: between myth and reality].

PMID- 8297967
TI  - [The physician-patient relation through a Balint group].
AB  - OBJECTIVE: To evaluate by means of a contents analysis a Balint Group (BG) after
      7 years in operation, to find which type of patients are most disturbing for the
      General Practitioner and to analyse the sort of feelings they provoke. DESIGN: A
      retrospective descriptive study which uses qualitative analysis methodology.
      SETTING: The BG under analysis was created in the heart of the Catalan Society of
      Family and Community Medicine in 1984. PATIENTS: 21 sessions were analysed,
      covering 18 patients. INTERVENTIONS: The variables studied were: the motives for
      presentation, the sort of patient presenting and the doctor's feeling towards
      them. MEASUREMENTS AND MAIN RESULTS: Two types of patients stood out: those with
      somatization disorders and those with a very poor prognosis. The first (12 out of
      18) unsettled the professional and caused him/her to lose grip on his/her role.
      The GP often trivialised their requests or thought they were pretending. Those
      sessions analysed where patients had a poor prognosis made clear the high degree
      of empathy shown by the doctor. Questions were raised as to how to tackle the
      illness both with the patient and his/her family. Feelings of distress, fear,
      anguish-exhaustion-impotence and rejection-aggression of the doctor towards
      particular patients were analysed. CONCLUSIONS: The questioning of the doctor's
      social role or professional identity by particular patients makes it difficult
      for him/her to maintain a long-term therapeutic relationship with them. The BG
      was useful for the participants, because of the group dynamic and also because
      they found out the possibilities and limitations of their treatment.

PMID- 8297968
TI  - [What has the reform of primary care meant in the community approach to arterial
      hypertension?].
AB  - OBJECTIVE: To evaluate an arterial Hypertension programme (AHP), with analysis of
      its feasibility and the problems inherent in the methodology used. DESIGN: A
      retrospective evaluation of the results of an AHP programme. A population
      projection of the results by means of an extrapolated calculation. SETTING: An
      urban Health Centre. PATIENTS: A random sample of 282 patients selected from the
      total of 564 individuals diagnosed with AHT over the 6 years of the programme's
      operation. MEASUREMENTS AND MAIN RESULTS: The 564 patients in the records made up
      16.5% of the Health Area's adult population. The iceberg phenomenon (the
      percentage of undiagnosed hypertension sufferers) has evolved from 59% in 1988 to
      the present 17%. 7.4% of the sample received no treatment. Average AHT figures
      for the patients in treatment were 143 +/- 15 mm Hg systolic pressure and 85 +/-
      9 mm Hg diastolic. 75% had adequate control of their tension figures (< 160/95).
      The population projection of these findings indicated that 57% of Hypertension
      sufferers calculated to be living in the Health area were diagnosed and
      monitored. CONCLUSIONS: The results show that the AHT situation among the
      population has substantially improved. The methodology used is easy to manage and
      can be of service in the evaluation of the impact of AHT programmes on the
      population.

PMID- 8297969
TI  - [The long-term treatment card from the user's viewpoint].
AB  - OBJECTIVE: To find the user's opinion of the long-term treatment card (LTC) as
      against repeat prescriptions from a medical clinic, the time employed on
      administration and information received on the use of the LTC. Criticisms and
      suggestions were gathered. DESIGN: Crossover, by means of questionnaires filled
      in by the subjects. SETTING: Almozara Health Centre, Zaragoza. PATIENTS AND OTHER
      PARTICIPANTS: 397 valid questionnaires given out to LTC users. The Primary Care
      team. MEASUREMENTS AND MAIN RESULTS: The LTC was preferred to a clinical
      prescription by 88% of those surveyed. 79% considered that they needed less time
      to obtain their prescriptions by using the LTC. 10% had difficulties in obtaining
      their treatment; 36% of them due to problems involving the collection/delivery
      timetable. 38% demanded the right to have medication included in the LTC: either
      at their own wish (18%), in the view of other INSALUD doctors (11%) or of any
      other medical officer (9%). 25% did not feel they were sufficiently informed.
      CONCLUSIONS: The LTC is very widely accepted. Information on its use and
      functioning should be improved, with special emphasis on the inclusion of
      medication solely by the General Practitioner concerned. The criticisms
      collected, such as insufficient control of lengthy treatments or adverse side
      effects, support the view that quality controls of the LTC are needed.

PMID- 8297970
TI  - [The coverage and quality of the follow-up in the prenatal care at a health
      center].
AB  - OBJECTIVE: To discover the recruitment and follow-up coverage of Prenatal Care in
      Parla Health Center, derivation causes and quality control of follow-up. DESIGN:
      Descriptive and retrospective study. PATIENTS: We obtained 445 newborns (from May
      1991 to April 1992) in pediatric records of Health Center, and encountered 412
      women records (93%). MEASUREMENTS AND MAIN RESULTS: We measured general
      practitioner coverage, obstetric derivation and causes, and audit of 23 quality
      markers selected. General practitioner diagnosed pregnancy in 142 cases (32%). Of
      them, 63 were derivated at the beginning, 19 at the following-up, and 60 cases
      (13.5% of total newborns known) were completed in primary care. In these, 19 of
      23 quality markers were fulfilled over 80%. CONCLUSIONS: We emphasized the poor
      capacity of primary care for recruiting pregnancies in the moment (most of them
      went straight to obstetric), and the excellent results of quality control
      markers. These situations can be as similar as many others Health Centers in
      urban areas. Coordination with Reference Obstetric Services is necessary as a
      strategy to increased the coverage of these programs.

PMID- 8297971
TI  - [Who is the infrequent patient?].
AB  - OBJECTIVE: To reach the rarely attending section of the population, in order to
      define its sociodemographic characteristics, and analyse its health status and
      use of the Health Services. DESIGN: Observational, crossover study, using a
      questionnaire. SETTING: Primary Care. PATIENTS: Patients over 19 assigned to four
      morning-shift doctors at the Parla Health Centre (Madrid) and who had not
      attended for health care over the preceding four years. INTERVENTION:
      Communication by letter and phone. Questionnaire. MEASUREMENTS AND MAIN RESULTS:
      5.07% (468) of the catchment population satisfied our criteria for inclusion.
      More than half of these could not be located. Only 51 (10.9%) could be
      interviewed; and 14 (2.99%) remained in the study. Gender accounted for no
      significant differences. No one was over 65. Self-perception of their own health
      status was good or very good in 85.7%. 85.7% were smokers. 71% said that they
      "rarely" attended for health care. One male had three cardiovascular risk
      factors. CONCLUSIONS: We found that finding the rarely attending person was not
      easy. The few cases analysed do not allow for extrapolation. Our findings showed
      he was a married 37-year old male with a steady job in the service sector. He
      smokes, doesn't drink and considers himself in a good state of health.

PMID- 8297972
TI  - [Tobacco dependence and its relation to certain variables in an urban basic
      health area].
AB  - OBJECTIVE: The prevalence of habitual tobacco use in our area and its
      relationship to other epidemiological variables. DESIGN: A highly structured
      interview was given to a random sample from the area in order to make a
      descriptive study of smokers' characteristics. Beforehand there had been: a pre
      interview, training of the interviewers, reliability. SETTING: The Arturo Eyries
      Base Health Area in Valladolid. PARTICIPANTS: A random sample of 246 people over
      14, extracted from a sampling background numbering 14,200. INTERVENTION: Items
      related to tobacco addiction and included in the interview. MEASUREMENTS AND MAIN
      RESULTS: 43.9% +/- 5 of our population smoked, consuming an average of 16.4 +/-
      10 (mean +/- SD) cigarettes per day. The average starting age was 17.2 +/- 5.4,
      with males starting earlier. The highest percentage of smokers was found in the
      30-39 age group, where female smokers exceeded female non-smokers. The typical
      smoker's profile is that of a married middle-aged man or woman, of average
      education and able to work. CONCLUSIONS: We obtained a section of the population
      at risk, clearly defined for health purposes.

PMID- 8297973
TI  - [New models of the relationship between primary care teams and mental health
      teams: the epidemiological bases for evaluation].

PMID- 8297974
TI  - [Adverse reactions to drugs and letters to the editor].

PMID- 8297975
TI  - [Nutritional status or food habits].

PMID- 8297976
TI  - [Emergencies in a rural doctor's office].

PMID- 8297978
TI  - [The routine ECG in healthy patients].

PMID- 8297977
TI  - [A hydatid cyst with an atypical location].

PMID- 8297979
TI  - [Cardiovascular risk factors in a population admitted for AMI in a general
      hospital].

PMID- 8297980
TI  - [Nongovernmental organizations and the development of primary care].

PMID- 8297981
TI  - [Joining a primary care practice: the basic questions].

PMID- 8297982
TI  - [Where is the market?].

PMID- 8297983
TI  - [The early detection of uterine cervix cancer. Is it a priority in Spain?].

PMID- 8297984
TI  - [Tuberculous infection in schoolchildren in the 1st year of basic general
      education in the Murcia region (1985-1992)].
AB  - OBJECTIVE: To find the evolution of the prevalence of tubercular infection.
      DESIGN: Study of the tendency of the findings from crossover surveys carried out
      during the last 7 years. SETTING: First-year EGB students from public and private
      schools in the Autonomous Community of Murcia. INTERVENTION: Performing the
      Mantoux intradermoreaction test with 2 UT of PPDRT23/TWEEN80 for the first 5
      years and 5 UT of PPDCT68/TWEEN80 the last 2, with any induration over 5 mm.
      being considered positive. A clinical study of school students found positive and
      of their family contacts. RESULTS: Coverage was established at about 80% (71,520
      tests studied), with prevalence diminishing from 0.97% to 0.44%, this
      establishing a downward tendency (p < 0.001). 6.5% of the tuberculin-test
      positive students (21) and 2.8% of the family contacts (34) were diagnosed with
      tuberculosis. CONCLUSIONS: At the moment we lack data to suggest an increase in
      endemic tuberculosis among the school population. The results mentioned justify
      tuberculosis surveys of school students, although low prevalence suggests that
      the age at which it is performed should be raised.

PMID- 8297985
TI  - [User satisfaction in primary care: the results of a home survey].
AB  - OBJECTIVE: To discover the general and specific levels of satisfaction of our
      Primary Care centre (PCC) users, such as their satisfaction with the new Primary
      Care structures; to determine the relationship between satisfaction and
      sociodemographic factors; and to study the possible influence of certain user
      attitudes on satisfaction. DESIGN: Descriptive crossover study by means of a door
      to-door survey. SETTING: A basic care unit of the Primary Care team of Number 3
      health zone of area 19, Alcoy. PATIENTS AND OTHER PARTICIPANTS: The survey had a
      sample of 312 users, obtained by means of systematic sampling on the basis of our
      PCC's records. MEASUREMENTS AND MAIN RESULTS: Satisfaction was scored on a scale
      from 1 (very satisfied) to 5 (not at all satisfied). Average general satisfaction
      was 2.08 +/- 0.8 (quite satisfied), which in general depended on the length of
      time waiting to be seen. Average waiting time was 30 minutes (+/- 25 min 55 s)
      and the number of calls to obtain an appointment was 5.4 (+/- 4.6). Specific
      satisfaction with different professionals was around 2 (quite satisfied), a score
      which became more favorable in the case of doctors, but without statistically
      significant differences from the rest of the professionals. Socio-demographic
      factors did not show any influence on satisfaction. CONCLUSIONS: The user is in
      general "quite satisfied" with the attendance received at the PCC, despite the
      average waiting times and numbers of prior calls needed to make an appointment,
      which are among the highest published. This should make us aware of users' health
      access difficulties and should therefore forestall any over-optimism in the
      evaluation of a result which was generally positive as to user satisfaction. All
      in all, abundant information was obtained, which will assist in correcting the
      more negative features of the running of our PCC.

PMID- 8297986
TI  - [The evaluation of a program of preventive activities. "Successes" obtained with
      smokers, heavy drinkers and obese patients].
AB  - OBJECTIVE: Evaluation of the Programme of Preventive Measures and Health
      Publicity (PPMHP) in light of the successes obtained on smokers, heavy drinkers
      and the obese over a 6-month monitoring period. DESIGN: A "before and after"
      intervention study, with no random allocation. SETTING: Manises Health Centre.
      PATIENTS AND OTHER PARTICIPANTS: Compliance with preventive measures and
      diagnoses were evaluated for 459 patients included in the PPMHP (up to June
      1992). Patients who were smokers, heavy drinkers or obese were selected out of
      301 patients included in the PPMHP (up to December 1991), with the aim of
      assessing the number and efficacy of the interventions over a 6-month monitoring
      period. MEASUREMENTS AND MAIN RESULTS: "Success" was defined as: giving up
      smoking, lowering the grams of alcohol consumed to under the limits at their
      diagnosis, reducing the Bodily Mass Index to below 25. The diagnoses made were as
      follows: 8.7% (CI 6-11.4%) with Arterial Hypertension; 34.9% (CI 30.4-39.4%)
      smokers; 9.2% (CI 6.6-11.8%) heavy drinkers; 66.9% (CI 62.1-71.7%) obese; and
      38.2% (CI 31.8-42.2%) with Hypercholesterolaemia. There was 5.8% success in
      smokers (CI 1.7-10.2%, p < 0.01); 23.3% in heavy drinkers (CI 15.3-30.7%, p <
      0.01); and 1.1% (p NS) in the obese. CONCLUSIONS: An important number of
      diagnoses, with low intervention and moderate but significant efficacy, resulted
      from the interventions made.

PMID- 8297987
TI  - [Are blood glucose controls performed with portable dosimeters valid? A
      comparison of the reliability and validity of 3 commonly used models].
AB  - OBJECTIVE: To evaluate and compare the reliability and validity for both normal
      and high glycaemia values of three models of glycaemia self-analysers: Reflolux,
      Glucocard and One Touch. DESIGN: Descriptive and crossover study. Validation of a
      measuring appliance through its comparison with a standard appliance.
      PARTICIPANTS: The sample was composed of 90 blood specimens chosen by suitability
      sampling. MEASUREMENTS AND MAIN RESULTS: The glycaemia in the specimens was
      measured simultaneously by each one of the self-analysers and the central
      laboratory. There was high reliability (reproducibility) among the self
      analysers, with correlation coefficients of 0.98, 0.97 and 0.98, with no
      statistically significant differences. As to intra-instrument reliability
      (repeatability), tested by analysing the variances of the differences, no
      statistically significant differences were found, except in the Glucocard self
      analyser which lost precision at high glycaemia levels. Validity or accuracy,
      measured by the method of taking the average of the differences, showed a
      systematic bias in the Reflolux model, which had a value of 22.3 mg/dl above the
      reference model, and in the One Touch of -16.3 mg/dl. The Glucocard was the most
      accurate with a value of -1.78 mg/dl. CONCLUSIONS: Portable glycaemia dosimeters
      are very useful in following up diabetic patients because of their high
      reliability, but are not useful in the diagnosis of diabetes because of their
      lack of accuracy. Before beginning to use a portable dosimeter, its
      characteristics in terms of reliability and validity must be known, in order to
      evaluate correctly its findings.

PMID- 8297988
TI  - [The medical and social aspects of Down's syndrome].
AB  - OBJECTIVE: To find what health care is received and the family, school and work
      integration of people with Down's syndrome (DS). DESIGN: Descriptive study.
      SETTING: Primary health care. Community framework. PATIENT AND OTHER
      PARTICIPANTS: DS (1 to 25) in Albacete capital. 42 out of 49 were interviewed.
      MEASUREMENTS AND MAIN RESULTS: A census and a questionnaire to the parents.
      Investigations carried out: hearing two or three times: 18 (42.8%); visual
      acuteness (> 5 years old) three or more times: 22 (61.1%); thyroid function and
      spinal column: 5 (11.9%); of those over 5, 9 (25%) were obese and 26 (72.2%)
      brushed their teeth daily; 14 parents (38.8%) had a fortnightly interview with
      the teachers; 12 (75%) received training in workshops and 5 worked. CONCLUSIONS:
      It is considered advisable to run the checks in the programme of the Spanish
      Foundation for DS Institutions (especially thyroid and neck) and to improve mouth
      dental hygiene and weight control. Greater coordination between work and work
      training is needed.

PMID- 8297989
TI  - [The recommendable frequency for performing electrocardiograms in the
      hypertension patient].
AB  - OBJECTIVE: To obtain information on how often electrocardiograms (ECG) should be
      carried out during hypertense patients' follow-up. DESIGN: A retrospective,
      descriptive study. SETTING: La Mina Primary Care Centre. PATIENTS: Out of 1780
      hypertense patients over 14 years old monitored at our Health Centre, 352 were
      selected by random sampling. MEASUREMENTS AND MAIN RESULTS: Their first ECG after
      the AHT diagnosis was analysed. Those patients with a normal initial ECG, a
      minimum of one year's monitoring, and absence of a chronic limitation of air
      flow, diabetes mellitus or cardiopathy were included in the study. The ECGs
      following the first ECG were analysed sequentially until an anomalous ECG was
      detected. Final sample: 98 patients (average age 53, SD 12.8; 33 men and 65
      women). 89 (91.8%) had light-to-moderate AHT. The average interval between the
      initial normal ECG and the first pathological ECG was 36 months (SD 16.9). The
      most common electrocardiographic irregularities were the T minor wave (34.5%),
      the greater unevenness of the ST (17.2%) and left ventricular hypertrophy
      (13.8%). A total of 29 patients presented a pathological ECG during an average
      monitoring period of 61 months (C.I. 95%; 50-72). These were only significantly
      different from the remaining 69 as regards age. Those patients over 54 (n = 51)
      had significantly more irregularities (21) than those under 55 (n = 47) (8
      irregularities) (p = 0.006), the main increase being between the ages of 55 and
      60. CONCLUSIONS: The recommendation to carry out an ECG every 2 or 3 years when
      monitoring a hypertense patient with a normal initial ECG and without additional
      pathologies, could be extrapolated from our study. The time interval could be
      shortened for older patients.

PMID- 8297990
TI  - [An exploration of factors that influence the frequency of the use of hospital
      emergency services and admissions].
AB  - OBJECTIVE: To examine how some factors connected with Continuous Care Points
      (CCP) affect attendance at hospital Casualty departments and admittance from
      them. DESIGN: Ecological study. SETTING: Leon Health area. PATIENTS AND OTHER
      PARTICIPANTS: All the CCP's belonging to the Leon Health area. MEASUREMENTS AND
      MAIN RESULTS: Average attendance at hospital Casualties was 15.7 per 1,000
      inhabitants per month. Those patients who brought with them a P10 form were more
      likely to be admitted (39.5% to 26.5%) than those who did not bring this form (p
      < 0.01). It was concluded from a regression analysis that the distance between
      the CCP and the hospital decisively affects attendance at hospital Casualties (r
      = -0.74) and that the admission rate is positively related to distance (r = 0.72)
      and negatively to the said attendance at Casualties (r = -0.77). CONCLUSION: Use
      of hospital Casualty departments increases as accessibility (distance) improves.
      Distance and the ageing of the population are factors which have an important
      effect on the admission rates from Casualties.

PMID- 8297991
TI  - [An evaluation of health promotion programs in primary care].

PMID- 8297992
TI  - [Childhood and juvenile ankylosing spondylitis].

PMID- 8297993
TI  - [Childhood and juvenile ankylosing spondylitis?].

PMID- 8297994
TI  - [Intervention to improve antibiotic prescription].

PMID- 8297995
TI  - [Introduction of continuous records in computerized filling of repeat
      prescriptions].

PMID- 8297996
TI  - [The prevalence of obesity in the general adult population].

PMID- 8297997
TI  - [A re-evaluation of the diabetes mellitus type 2 program. A proposal for a
      quality indicator].

PMID- 8297998
TI  - [The use of antibiotic therapy in urinary tract infections].

PMID- 8297999
TI  - [Beta-thalassemia minor in primary care].

PMID- 8298000
TI  - [An improvement in the hypoxemia after almitrine treatment in patients with
      chronic obstructive pulmonary diseases].

PMID- 8298001
TI  - [The companion in the clinical interview].

PMID- 8298002
TI  - [The medical visit].

PMID- 8298003
TI  - Virus dynamics lead to structure, by George!

PMID- 8298004
TI  - Modeling of macromolecular diffusion in congested media.

PMID- 8298005
TI  - Testing the limits of flagellar motors.

PMID- 8298006
TI  - To fuse or not to fuse?

PMID- 8298007
TI  - A closer look at how membrane proteins move.

PMID- 8298008
TI  - Distribution of voltage sensors in mammalian outer hair cells.

PMID- 8298009
TI  - High microfilament concentration results in barbed-end ADP caps.
AB  - Current theory and experiments describing actin polymerization suggest that site
      specific cleavage of bound nucleotide following F-actin filament formation causes
      the barbed ends of microfilaments to be capped first with ATP subunits, then with
      ADP bound to inorganic phosphate (ADP.Pi) at steady-state. The barbed ends of
      depolymerizing filaments consist of ADP subunits. The decrease in stability of
      the barbed-end cap accompanying the transition from ADP.Pi to ADP allows
      nucleotide hydrolysis and subsequent loss of Pi to regulate F-actin filament
      dynamics. We describe a novel computational model of nucleotide capping that
      simulates both the spatial and temporal properties of actin polymerization. This
      model has been used to test the effects of high filament concentration on the
      behavior of the ATP hydrolysis cycle observed during polymerization. The model
      predicts that under conditions of high microfilament concentration an ADP cap can
      appear during steady-state at the barbed ends of filaments. We show that the
      presence of the cap can be accounted for by a kinetic model and predict the
      relationship between the nucleotide concentration ratio [ATP]/[ADP], the F-actin
      filament concentration, and the steady-state distribution of barbed-end ADP cap
      lengths. The possible consequences of this previously unreported phenomenon as a
      regulator of cytoskeletal behavior are discussed.

PMID- 8298010
TI  - Microspectrofluorometry of the protonation state of ellipticine, an antitumor
      alkaloid, in single cells.
AB  - The protonation state and intracellular distribution of ellipticine were
      investigated in single human mammary T47D cells by confocal laser
      microspectrofluorimetry. In the cell nucleus, only the protonated form of
      ellipticine was detected as a direct consequence of its apparent pK increase upon
      DNA binding. Both protonated and neutral forms were present in the aqueous
      cytoplasm, where the pH is close to the drug pK. When cells were incubated in
      high concentrations of K+, a condition that depolarizes the plasma membrane
      potential, ellipticine cellular accumulation was reduced. In the cytoplasm,
      ellipticine was mainly bound to mitochondria, and its protonation equilibrium was
      shifted toward the neutral form. The fluorescence spectrum of ellipticine bound
      to mitochondria was insensitive to valinomycin, whereas it was markedly shifted
      toward the protonated form after carbonyl cyanide p-trifluoromethoxy
      phenylhydrazone or nigericin addition. Similar studies with ellipticine bound to
      isolated mitochondria suggest that it behaves as a fluorescent probe of
      mitochondrial pH in both isolated mitochondria and single living cells.

PMID- 8298011
TI  - Vulnerability in an excitable medium: analytical and numerical studies of
      initiating unidirectional propagation.
AB  - Cardiac tissue can display unusual responses to certain stimulation protocols. In
      the wake of a conditioning wave of excitation, spiral waves can be initiated by
      applying stimuli timed to occur during a period of vulnerability (VP). Although
      vulnerability is well known in cardiac and chemical media, the determinants of
      the VP and its boundaries have received little theoretical and analytical study.
      From numerical and analytical studies of reaction-diffusion equations, we have
      found that 1) vulnerability is an inherent property of Beeler-Reuter and FitzHugh
      Nagumo models of excitable media; 2) the duration of the vulnerable window (VW)
      the one-dimensional analog of the VP, is sensitive to the medium properties and
      the size of the stimulus field; and 3) the amplitudes of the excitatory and
      recovery processes modulate the duration of the VW. The analytical results reveal
      macroscopic behavior (vulnerability) derived from the diffusion of excitation
      that is not observable at the level of isolated cells or single reaction units.

PMID- 8298012
TI  - Monte Carlo simulation of lipid mixtures: finding phase separation.
AB  - The nonideal mixing of phosphatidylserine (PS) and phosphatidylcholine (PC)
      binary lipid mixtures was studied by computer simulation based on a model wherein
      the excess energy of mixing is divided between an electrostatic term and one
      adjustable term delta Em that includes all other nonideal interactions. The
      lateral distribution of the lipids and the energy of the mixtures were obtained
      by using Kawasaki relaxation in a canonical ensemble. The Gibbs free energies
      were calculated by Kirkwood's coupling parameter method. The simulation results
      are strongly dependent on simulation size for sizes smaller than about 1000
      lipids. Nonideal interaction between lipids can result in large scale separation
      of lipid phases of different composition at reasonable delta Em values as well as
      clustering of like lipids. In plots of total Gibbs free energy of mixing versus
      PS mole fraction in PS/PC, the boundaries of the two phase region could be
      accurately determined. The electrostatic interaction influences cluster size and
      shape, and also the composition of phases in the two-phase region.

PMID- 8298013
TI  - A molecular model for lipid-protein interaction in membranes: the role of
      hydrophobic mismatch.
AB  - The interaction free energy between a hydrophobic, transmembrane, protein and the
      surrounding lipid environment is calculated based on a microscopic model for
      lipid organization. The protein is treated as a rigid hydrophobic solute of
      thickness dP, embedded in a lipid bilayer of unperturbed thickness doL. The lipid
      chains in the immediate vicinity of the protein are assumed to adjust their
      length to that of the protein (e.g., they are stretched when dP > doL) in order
      to bridge over the lipid-protein hydrophobic mismatch (dP-doL). The bilayer's
      hydrophobic thickness is assumed to decay exponentially to its asymptotic,
      unperturbed, value. The lipid deformation free energy is represented as a sum of
      chain (hydrophobic core) and interfacial (head-group region) contributions. The
      chain contribution is calculated using a detailed molecular theory of chain
      packing statistics, which allows the calculation of conformational properties and
      thermodynamic functions (in a mean-field approximation) of the lipid tails. The
      tails are treated as single chain amphiphiles, modeled using the rotational
      isometric state scheme. The interfacial free energy is represented by a
      phenomenological expression, accounting for the opposing effects of head-group
      repulsions and hydrocarbon-water surface tension. The lipid deformation free
      energy delta F is calculated as a function of dP-doL. Most calculations are for
      C14 amphiphiles which, in the absence of a protein, pack at an average area per
      head-group ao approximately equal to 32 A2 (doL approximately 24.5 A),
      corresponding to the fluid state of the membrane. When dP = doL, delta F > 0 and
      is due entirely to the loss of conformational entropy experienced by the chains
      around the protein. When dP > doL, the interaction free energy is further
      increased due to the enhanced stretching of the tails. When dP < doL, chain
      flexibility (entropy) increases, but this contribution to delta F is overcounted
      by the increase in the interfacial free energy. Thus, delta F obtains a minimum
      at dP-doL approximately 0. These qualitative interpretations are supported by
      detailed numerical calculations of the various contributions to the interaction
      free energy, and of chain conformational properties. The range of the
      perturbation of lipid order extends typically over few molecular diameters. A
      rather detailed comparison of our approach to other models is provided in the
      discussion.

PMID- 8298014
TI  - Brownian dynamics simulations of probe and self-diffusion in concentrated protein
      and DNA solutions.
AB  - We have developed a Brownian dynamics algorithm for simulating probe and self
      diffusion in concentrated solutions of DNA and protein. In these simulations,
      proteins are represented as spheres with radii given by their hydrodynamic radii,
      while DNA is modeled as a wormlike chain of hydrodynamically equivalent spherical
      frictional elements. The molecular interaction potentials employed by the program
      allow for intramolecular stretching and bending motions of the DNA chains, short
      range Lennard-Jones interactions, and long-range electrostatic interactions. To
      test the program, we have carried out simulations of bovine serum albumin (BSA)
      probe diffusion and DNA self-diffusion in solutions of short-chain DNA as a
      function of both DNA concentration and solution ionic strength. In addition, we
      report on simulations of BSA self-diffusion as a function of BSA concentration
      and ionic strength. Based on a comparison to available experimental data, we find
      that our simulations accurately predict these transport properties under
      conditions of physiological salt concentration and predict the stronger
      concentration dependence observed at lower salt concentrations. These results are
      discussed in light of the nature of the intermolecular interactions in such
      systems and the approximations and limitations of the simulation algorithm.

PMID- 8298015
TI  - Calorimetric studies of freeze-induced dehydration of phospholipids.
AB  - Differential scanning calorimetry (DSC) was used to determine the amount of water
      that freezes in an aqueous suspension of multilamellar
      dipalmitoylphosphatidylcholine (DPPC) liposomes. The studies were performed with
      dehydrated suspensions (12-20 wt% water) and suspensions containing an excess of
      water (30-70 wt% water). For suspensions that contained > or = 18 wt% water, two
      ice-formation events were observed during cooling. The first was attributed to
      heterogeneous nucleation of extraliposomal ice; the second was attributed to
      homogeneous nucleation of ice within the liposomes. In suspensions with an
      initial water concentration between 13 and 16 wt%, ice formation occurred only
      after homogeneous nucleation at temperatures below -40 degrees C. In suspensions
      containing < 13 wt% water, ice formation during cooling was undetectable by DSC,
      however, an endotherm resulting from ice melting during warming was observed in
      suspensions containing > or = 12 wt% water. In suspensions containing < 12 wt%
      water, an endotherm corresponding to the melting of ice was not observed during
      warming. The amount of ice that formed in the suspensions was determined by using
      an improved procedure to calculate the partial area of the endotherm resulting
      from the melting of ice during warming. The results show that a substantial
      proportion of water associated with the polar headgroup of phosphatidylcholine
      can be removed by freeze-induced dehydration, but the amount of ice depends on
      the thermal history of the samples. For example, after cooling to -100 degrees C
      at rates > or = 10 degrees C/min, a portion of water in the suspension remains
      supercooled because of a decrease in the diffusion rate of water with decreasing
      temperature. A portion of this supercooled water can be frozen during subsequent
      freeze-induced dehydration of the liposomes under isothermal conditions at
      subfreezing storage temperature Ts. During isothermal storage at Ts > or = -40
      degrees C, the amount of unfrozen water decreased with decreasing Ts and
      increasing time of storage. After 30 min of storage at Ts = -40 degrees C and
      subsequent cooling to -100 degrees C, the amount of water associated with the
      polar headgroups was < 0.1 g/g of DPPC. At temperatures > -50 degrees C, the
      amount of unfrozen water associated with the polar headgroups of DPPC decreased
      with decreasing temperature in a manner predicted from the desorption isotherm of
      DPPC. However, at lower temperatures, the amount of unfrozen water remained
      constant, in large part, because the unfrozen water underwent a liquid-to-glass
      transformation at a temperature between -50 degrees and -140 degrees C.

PMID- 8298016
TI  - Studies of mixed-chain diacyl phosphatidylcholines with highly asymmetric acyl
      chains: a Fourier transform infrared spectroscopic study of interfacial hydration
      and hydrocarbon chain packing in the mixed interdigitated gel phase.
AB  - The mixed interdigitated gel phases of unlabeled, specifically 13C = O-labeled,
      and specifically chain-perdeuterated samples of 1-O-eicosanoyl, 2-O-lauroyl
      phosphatidylcholine and 1-O-decanoyl, 2-O-docosanoyl phosphatidylcholine were
      studied by infrared spectroscopy. Our results suggest that at the liquid
      crystalline/gel phase transition temperatures of these lipids, there is a greater
      redistribution in the populations of free and hydrogen-bonded ester carbonyl
      groups than is commonly observed with symmetric chain n-saturated diacyl
      phosphatidylcholines. The formation of the mixed interdigitated gel phase
      coincides with the appearance of a marked asymmetry in the contours of the C = O
      stretching band, a process which becomes more pronounced as the temperature is
      reduced. This asymmetry is ascribed to the emergence of a predominant lipid
      population consisting of free sn1- and hydrogen-bonded (hydrated) sn2-ester
      carbonyl groups. This suggests that the region of the mixed interdigitated
      bilayer polar/apolar interface near to the sn1-ester carbonyl group is less
      hydrated than is the case with the noninterdigitated gel-phase bilayers formed by
      normal symmetric chain phosphatidylcholines. In the methylene deformation region
      of the spectrum, the unlabeled lipids exhibit a pronounced splitting of the CH2
      scissoring bands. This splitting is significantly attenuated when the short
      chains are perdeuterated and collapses completely upon perdeuteration of the long
      chains, irrespective of whether the long (or short) chains are esterified to the
      sn1 or sn2 positions of the glycerol backbone. These results are consistent with
      a global hydrocarbon chain packing motif in which the zigzag planes of the
      hydrocarbon chains are perpendicular to each other and the sites occupied by long
      chains are twice as numerous as those occupied by short chains. The experimental
      support for this chain-packing motif enabled more detailed considerations of the
      possible ways in which these lipid molecules are assembled in the mixed
      interdigitated gel phase. Generally, our results are compatible with a previously
      proposed model in which the mixed interdigitated gel phase is an assembly of
      repeat units which consists of two phosphatidylcholine molecules forming a triple
      chain structure with the long chains traversing the bilayer and with the methyl
      termini of the shorter chains opposed at the bilayer center. Our data also
      suggest that the packing format which is most consistent with our results and
      previously published work is one in which the hydrocarbon chains of each repeat
      unit are parallel to each other with the repeat units themselves being
      perpendicularly packed.

PMID- 8298017
TI  - Actin binding to lipid-inserted alpha-actinin.
AB  - The interaction of alpha-actinin with lipid films and actin filaments was
      investigated. First alpha-actinin was incorporated in lipid films at the
      air/water interface. Injection of alpha-actinin into the subphase of a lipid
      monolayer led to a significant increase of the surface pressure only for lipid
      films consisting of a mixture of a negatively charged lipid with a high
      proportion of diacylglycerol. These alpha-actinin-containing films were
      transferred onto silanized quartz slides. Photobleaching experiments in the
      evanescent field allowed quantification of the lateral number density of the
      lipid-bound alpha-actinin. In combination with the area increase from the
      monolayer experiments, the photobleaching measurements suggest that alpha-actinin
      is incorporated into the lipid film in such a way that actin binding sites are
      accessible from the bulk phase. Binding experiments confirmed that the alpha
      actinin selectively binds actin filaments in this configuration. We also showed
      that, in contrast to actin filaments which are adsorbed directly onto planar
      surfaces, the alpha-actinin-bound actin filaments are recognized and cleaved by
      the actin-severing protein gelsolin. Thus we have constructed an in vitro system
      which opens new ways for investigations of membrane-associated actin-binding
      proteins and of the physical behavior of actin filaments in the close
      neighborhood to membranes.

PMID- 8298018
TI  - A single order-disorder transition generates tension during the Huxley-Simmons
      phase 2 in muscle.
AB  - Increasing temperature was used to progressively interconvert non-force
      generating into force-generating states in skinned rabbit psoas muscle fibers
      contracting isometrically. Laser temperature-jump and length-jump experiments
      were used to characterize tension generation in the time domain of the Huxley
      Simmons phase 2. In our experiments, phase 2 is subdivisible into two kinetic
      steps each with quite different physical properties. The fast kinetic component
      has rate constant of 950 s-1 at 1 degrees C and a Q10 of approximately 1.2. Its
      rate is tension insensitive and its normalized amplitude declines with rising
      temperature--behavior that closely parallels the instantaneous stiffness of the
      cross-bridge. It is likely that this kinetic step is a manifestation of a damped
      elastic element/s in the fiber. The slow component of phase 2 is temperature
      dependent with a Q10 of approximately 3.0. Its rate is sensitive to tension.
      Unlike the fast component, its amplitude remains in fixed proportion to isometric
      tension at different temperatures indicating direct participation in tension
      generation. Similar T-jump studies on frog fibers are also included. The combined
      results (frog and rabbit) suggest that tension generation occurs in a single
      endothermic (entropy driven) step in phase 2.

PMID- 8298019
TI  - Adiabatic compressibility of myosin subfragment-1 and heavy meromyosin with or
      without nucleotide.
AB  - The partial specific adiabatic compressibilities of myosin subfragment-1 (S1) and
      heavy meromyosin (HMM) of skeletal muscle in solution were determined by
      measuring the density and the sound velocity of the solution. The partial
      specific volumes of S1 and HMM were 0.713 and 0.711 cm3/g, respectively. The
      partial specific adiabatic compressibilities of S1 and HMM were 4.2 x 10(-12) and
      2.9 x 10(-12) cm2/dyn, respectively. These values are in the same range as the
      most of globular proteins so far studied. The result indicates that the
      flexibility of S1 region almost equals to that of HMM. After binding to
      ADP.orthovanadate, S1 and HMM became softer than their complexes with ADP. The
      bulk moduli of S1 and HMM were of the order of (4-6) x 10(10) dyn/cm2, which are
      very comparable with the bulk modulus of muscle fiber.

PMID- 8298020
TI  - Characterization of beta-connectin (titin 2) from striated muscle by dynamic
      light scattering.
AB  - Connectin (titin) is a large filamentous protein (single peptide) with a
      molecular mass of approximately 3 MDa, contour length approximately 900 nm, and
      diameter approximately 4 nm, and resides in striated muscle. Connectin links the
      thick filaments to the Z-lines in a sarcomere and produces a passive elastic
      force when muscle fiber is stretched. The aim of this study is to elucidate some
      aspects of physical properties of isolated beta-connectin (titin 2), a
      proteolytic fragment of connectin, by means of dynamic light-scattering (DLS)
      spectroscopy. The analysis of DLS spectra for beta-connectin gave the
      translational diffusion coefficient of 3.60 x 10(-8) cm2/s at 10 degrees C (or
      the hydrodynamic radius of 44.1 nm), molecular mass little smaller than 3.0 MDa
      (for a literature value of sedimentation coefficient), the root-mean-square end
      to-end distance of 163 nm (or the radius of gyration of 66.6 nm), and the Kuhn
      segment number of 30 and segment length of 30 nm (or the persistence length of 15
      nm). These results permitted to estimate the flexural rigidity of 6.0 x 10(-20)
      dyn x cm2 for filament bending, and the elastic constant of 7 dyn/cm for
      extension of one persistence length. Based on a simple model, implications of the
      present results in muscle physiology are discussed.

PMID- 8298021
TI  - Raman spectroscopy of DNA-metal complexes. I. Interactions and conformational
      effects of the divalent cations: Mg, Ca, Sr, Ba, Mn, Co, Ni, Cu, Pd, and Cd.
AB  - Interactions of divalent metal cations (Mg2+, Ca2+, Ba2+, Sr2+, Mn2+, Co2+, Ni2+,
      Cu2+, Pd2+, and Cd2+) with DNA have been investigated by laser Raman
      spectroscopy. Both genomic calf-thymus DNA (> 23 kilobase pairs) and
      mononucleosomal fragments (160 base pairs) were employed as targets of metal
      interaction in solutions containing 5 weight-% DNA and metal:phosphate molar
      ratios of 0.6:1. Raman difference spectra reveal that transition metal cations
      (Mn2+, Co2+, Ni2+, Cu2+, Pd2+, and Cd2+) induce the greatest structural changes
      in B-DNA. The Raman (vibrational) band differences are extensive and indicate
      partial disordering of the B-form backbone, reduction in base stacking, reduction
      in base pairing, and specific metal interaction with acceptor sites on the purine
      (N7) and pyrimidine (N3) rings. Many of the observed spectral changes parallel
      those accompanying thermal denaturation of B-DNA and suggest that the metals link
      the bases of denatured DNA. While exocyclic carbonyls of dT, dG, and dC may
      stabilize metal ligation, correlation plots show that perturbations of the
      carbonyls are mainly a consequence of metal-induced denaturation of the double
      helix. Transition metal interactions with the DNA phosphates are weak in
      comparison to interactions with the bases, except in the case of Cu2+, which
      strongly perturbs both base and phosphate group vibrations. On the other hand,
      the Raman signature of B-DNA is largely unperturbed by Mg2+, Ca2+, Sr2+, and
      Ba2+, suggesting much weaker interactions of the alkaline earth metals with both
      base and phosphate sites. A notable exception is a moderate perturbation by
      alkaline earths of purine N7 sites in 160-base pair DNA, with Ca2+ causing the
      greatest effect. Correlation plots demonstrate a strong interrelationship between
      perturbations of Raman bands assigned to ring vibrations of the bases and those
      of bands assigned to exocyclic carbonyls and backbone phosphodiester groups.
      However, strong correlations do not occur between the Raman phosphodioxy band
      (centered near 1092 cm-1) and other Raman bands, suggesting that the former is
      not highly sensitive to the structural changes induced by divalent metal cations.
      The structural perturbations induced by divalent cations are much greater for >
      23-kilobase pair DNA than for 160-base pair DNA, as evidenced by both the Raman
      difference spectra and the tendency toward the formation of insoluble aggregates.
      In the presence of transition metals, aggregation of high-molecular-weight DNA is
      evident at temperatures as low as 11 degrees C. A relationship between DNA
      melting and aggregation is proposed in which initial metal binding at major
      groove sites locally destabilizes the B-DNA double helix, causing displacement of
      the bases away from one another and exposing additional metal binding sites.
      Metal cation linkage of two displaced bases would allow separate DNA strands to
      crosslink. Aggregation is proposed to result from the formation of an extended
      network of these crosslinks.

PMID- 8298022
TI  - A model-independent approach to assigning bacteriorhodopsin's intramolecular
      reactions to photocycle intermediates.
AB  - By using factor analysis and decomposition, bacteriorhodopsin's intramolecular
      reactions have been assigned to photocycle intermediates. Independent of specific
      kinetic models, the pure BR-L, BR-M, BR-N, and BR-O difference spectra were
      calculated by analyzing simultaneously two different measurements in the visible
      and infrared spectral region performed at pH 6.5, 298 K, 1 M KCl, and pH 7.5, 288
      K, 1 M KCl. Even though after M formation L, M, N, and O intermediates
      kinetically overlap under physiological conditions, their pure spectra have been
      separated by this analysis in contrast to other approaches at which
      unphysiological conditions or mutants have been used or specific photocycle
      models have been assumed. The results now provide a set reference spectra for
      further studies. The following conclusions for physiologically relevant reactions
      are drawn: (a) the catalytic proton release binding site, asp 85, is protonated
      in the L to M transition and remains protonated in the intermediates N and O; (b)
      the catalytic proton uptake binding site asp 96 is deprotonated in the M to N
      transition and already reprotonated in the N to O transition; (c) proton transfer
      between asp 96 and the Schiff base is facilitated by backbone movements of a few
      peptide carbonyl groups in the M to N transition.

PMID- 8298023
TI  - The effect of iron displacement out of the porphyrin plane on the resonance Raman
      spectra of heme proteins and iron porphyrins.
AB  - The causes of the strong coupling of the iron-histidine vibration to the Soret
      resonance in the resonance Raman spectra of deoxyhemoglobin, myoglobin, and
      peroxidase are explored, using the vibronic theory. It is shown that the extent
      of the iron displacement out of the plane of the porphyrin nitrogens is the main
      structural parameter controlling the Fe-NHis band features, such as the
      dependence of its frequency and intensity on the protein conformation and number
      of the axial ligands, time evolution after the photolysis of the diatomic
      complexes of the proteins under consideration, and inverse relationship between
      the changes Fe-NHis and v4 porphyrin breathing mode frequencies.

PMID- 8298024
TI  - Effect of disordered hemes on energy transfer rates between tryptophans and heme
      in myoglobin.
AB  - Our recent linear dichroism study of heme transitions (Gryczynski, Z., E. Bucci,
      and J. Kusba. 1993. Photochem. Photobiology. in press) indicate that heme cannot
      be considered a planar oscillator when it acts as an acceptor of radiationless
      excitation energy transfer from tryptophan. The linear nature of the heme
      absorption transition moment in the near-UV region implies a strong dependence of
      the transfer rate factors on the relative angular position of the heme and
      tryptophan, i.e., on the kappa 2 orientation parameter of the Forster equation.
      Using the atomic coordinates of SW myoglobin we have estimated the variation of
      kappa 2 parameter as a function of the heme absorption transition moment
      direction. The simulations proved that transfer is very efficient and anticipates
      lifetimes in the picosecond range. Also, they showed that transfer is very
      sensitive to rotations of the heme around its alpha-gamma-meso-axis, which may
      reduce the efficiency of transfer to almost zero values, producing lifetimes very
      similar to those of free tryptophan, in the nanosecond range. Comparisons between
      the lifetime values reported in the literature and those here estimated suggest
      that natural heme disorder, in which heme is rotated 180 degrees around its meso
      axis, is at the origin of the nanosecond lifetimes found in myoglobin systems.

PMID- 8298025
TI  - Metastable CO binding sites in the photoproduct of a novel cooperative dimeric
      hemoglobin.
AB  - The infrared absorption spectrum of the CO-photoproduct from Scapharca
      inaequivalvis hemoglobin (Hbl) at 10 K yields only a single line in the "B" state
      region at 2132 cm-1. This is the same frequency as the B1 line observed in
      photodissociated vertebrate HbCO and MbCO. No evidence was found for the B2 line
      detected in vertebrate hemoglobins and myoglobin in the 2118-2120 cm-1 region.
      These data demonstrate that the protein does not have the same conformationally
      accessible ligand-binding sites as do vertebrate hemoglobins and myoglobins. The
      absence of the B2 line indicates that only a single weak site is accessible to
      the photolyzed CO molecule. These results are in accord with geminate rebinding
      experiments and ligand escape pathway calculations which have shown that the
      distal properties of Hbl are distinct from those of tetrameric hemoglobins and
      vertebrate myoglobins.

PMID- 8298026
TI  - Raman dynamic probe of hydrogen exchange in bean pod mottle virus: base-specific
      retardation of exchange in packaged ssRNA.
AB  - We describe a novel approach to investigating exchange kinetics in biological
      assemblies. The method makes use of a Raman multichannel analyzer coupled with a
      dialysis flow cell. We employ this methodology to determine exchange rates of
      labile hydrogens in both the packaged RNA genome and protein subunits of bean pod
      mottle virus (BPMV). In the BPMV assembly, which is similar to human
      picornaviruses, the x-ray structure indicates that about 20% of the ssRNA chain
      is ordered at the threefold vertices of the icosahedral capsid, although the
      nucleotide bases in the ordered segments are not known (Chen et al., 1989). Here,
      we compare exchange profiles of the native virus with those of the empty capsid,
      model nucleic acids and aqueous solvent to reveal the following exchange
      characteristics of BPMV RNA and protein: (i) Base-specific retardation of
      exchange is observed in the packaged RNA. (ii) Retardation is greatest for uracil
      residues, for which the first-order exchange rate constant (kU = 0.18 +/- 0.02
      min-1) is 40% lower than that of either the H2O solvent or adenine or cytosine
      groups of RNA (ksolv approximately kA approximately kC = 0.30 +/- 0.02 min-1).
      (iii) Retardation of exchange is also observed for the guanine residues of
      packaged RNA. (iv) No appreciable exchange of amide NH groups of capsid subunits
      occurs within the time of complete exchange (t approximately 10 min) of packaged
      RNA or bulk solvent. Thus, the present results identify sites in both the protein
      subunits (amide NH) and RNA nucleotides (amino NH2 and imino NH) which are
      resistant to solvent-catalyzed hydrogen exchange. We propose that retardation of
      exchange of labile sites of the RNA nucleotides is a consequence of the
      organization of the RNA chromosome within the virion. Our findings support a
      model for BPMV in which surface and buried domains of capsid subunits are
      extensively and rigidly hydrogen-bonded, and in which uracil and guanine
      exocyclic donor groups of packaged RNA are the principal targets for subunit
      interaction at the threefold vertices of the capsid.

PMID- 8298027
TI  - Quantitation of cytosolic [Ca2+] in whole perfused rat hearts using Indo-1
      fluorometry.
AB  - Fluorometric determination of cytosolic calcium, [Ca2+]c, using Indo-1 in intact
      tissue, is limited by problems in obtaining calibration parameters for Indo-1 in
      vivo. Therefore, the goal of this study was to calibrate Indo-1 using in vitro
      constants, obtained from protein-containing reference solutions designed to
      produce similar Indo-1 spectral properties to those in vivo. Due to wavelength
      dependent tissue light absorbance, the in vitro constants had to be absorbance
      corrected using a novel method. The correction factor was calculated from the
      relationship between the Indo-1 fluorescence intensities at the two detection
      wavelengths. A mixture of proteins at approximately 28 mg/ml had a similar Indo-1
      isosbestic wavelength (430 nm) to that found in vivo (427 nm), and a similar
      fluorescence ratio maximum with saturating Ca2+ to that found in vivo (after
      absorbance correction). Using calibration constants from this protein mixture,
      calculated [Ca2+]c in a Langendorf perfused rat heart was 187 nM during diastole,
      and 464 nM in systole. This new calibration method circumvented the considerable
      experimental problems of previous methods which required measurements with the
      cytosol fully depleted and fully saturated with Ca2+.

PMID- 8298028
TI  - Investigation of factors affecting fluorometric quantitation of cytosolic [Ca2+]
      in perfused hearts.
AB  - The goal of these studies was to examine the effects of several factors that may
      artifactually influence quantitation of cytosolic [Ca2+], [Ca2+]c, while using
      the fluorescent calcium indicator Indo-1. The following factors were
      investigated: 1) a possible fluorescence contribution from unhydrolized Indo-1/AM
      (by Mn2+ quenching), 2) Ca2+ buffering by Indo-1 (by varying [Indo-1]), 3)
      endothelial and mitochondrial Indo-1 loading (by bradykinin stimulation and
      calculations), and 4) effects of changing tissue fluorescence (predominantly
      NAD(P)H) on calculated [Ca2+]c during hypoxia (by a new method which allowed
      simultaneous determination of [Ca2+]c and changes in [NAD(P)H]). No significant
      contribution of Indo-1/AM was found. With increasing [Indo-1], calculated
      systolic [Ca2+]c fell significantly. Indo-1 incorporation (< 18%) into
      endothelial cells, caused a slight underestimation of systolic [Ca2+]c, while
      mitochondrial Indo-1 loading may cause overestimation of [Ca2+]c. With increased
      tissue fluorescence, during hypoxia, systolic [Ca2+]c may be underestimated by
      approximately 27% (for Indo-1 loading factors three to five times original tissue
      fluorescence). These studies suggest conditions in which experimental artifacts
      could be minimized to allow reliable quantitation of [Ca2+]c in intact perfused
      hearts using Indo-1 fluorometry. The major problem of obtaining reliable results
      depended on the ability to correct for changing NAD(P)H fluorescence while
      keeping [Indo-1] low.

PMID- 8298029
TI  - Calcium ion interactions with insoluble phospholipid monolayer films at the A/W
      interface. External reflection-absorption IR studies.
AB  - External reflection Fourier transform infrared (FT-IR) experiments are reported
      for insoluble monomolecular films of an equimolar mixture of 1,2
      dipalmitoylphosphatidylcholine (DPPC) and 1,2-dipalmitoylphosphatidylserine
      (DPPS) at the A/W interface as a function of surface pressure and Ca2+ ion
      presence. The separate components showed a surface pressure-induced
      conformational ordering of the acyl chains. The conformational ordering occurred
      more cooperatively for the DPPS. Acyl chain perdeuteration of the DPPC permitted
      the observation of the response of the individual components in the binary
      mixture to changes in surface tension and to the presence of Ca2+. Plots of
      surface pressure versus CH2 or CD2 stretching frequencies were analyzed with a
      two-state model. At each surface pressure within the two-state region, the
      fraction of disordered form was the same for each lipid component, suggesting
      that they are well mixed on the surface. Calcium ion (5 mM in the subphase)
      produces almost no effect on the pressure-induced acyl chain ordering of the DPPC
      in a single component film, whereas the same levels of Ca2+ induce acyl chain
      ordering at all surface pressures in both components of the binary mixture. Thus,
      unlike the bulk phase mixture of DPPC/DPPS, the binary lipids in this mixed
      monolayer film appear to retain their miscibility in the presence of Ca2+.
      Finally, Ca(2+)-induced dehydration of the phosphate group was observed through
      characteristic frequency shifts in the asymmetric PO2- stretching mode.

PMID- 8298030
TI  - Gap junction gating sensitivity to physiological internal calcium regardless of
      pH in Novikoff hepatoma cells.
AB  - Gap junction conductance (Gj) and channel gating sensitivity to voltage, Ca2+,
      H+, and heptanol were studied by double whole-cell clamp in Novikoff hepatoma
      cell pairs. Channel gating was observed at transjunctional voltages (Vj) > +/- 50
      mV. The cells readily uncoupled with 1 mM 1-heptanol. With heptanol, single (gap
      junctional) channel events with unitary conductances (gamma j) of 46 and 97 pS
      were detected. Both Ca(2+)-loading (EGTA.Ca) and acidifying (100% CO2) solutions
      caused uncoupling. However, CO2 was effective when Ca2+i was buffered with EGTA
      (a H(+)-sensitive Ca-buffer) but not with BAPTA (1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid) (a H(+)-insensitive Ca-buffer), suggesting a Ca(2+)
      mediated H+ effect on gap junctions. This was tested by monitoring the Gj decay
      at different pCai values (9, 6.9, 6.3, 6, and 5.5; 1 mM BAPTA) and pHi values
      (7.2 or 6.1, 10 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid and 2-(N
      morpholino)ethansulphonic acid, respectively). With pCai > or = 6.9 (pH 7.2 or
      6.1), Gj decreased to 10-70% of initial values in approximately 40 min, following
      single exponential decays (tau = approximately 28 min). With pCai 6-6.3 (pH 7.2
      or 6.1), Gj decreased to 10-25% of initial values in 15 min (tau = approximately
      5 min); the Student t gave a P = 0.0178. With pCa 5.5 the cells uncoupled in less
      than 1 min (tau = approximately 20 s). Low pHi affected neither time course nor
      shape of Gj decay at any pCai tested. The data indicate that these gap junctions
      are sensitive to [Ca2+]i in the physiological range (< or = 500 nM) and that low
      pHi, without an increase in [Ca2+]i, neither decreases Gj nor increases channel
      sensitivity to Ca2+.

PMID- 8298031
TI  - Temperature dependence of unitary properties of an ATP-dependent potassium
      channel in cardiac myocytes.
AB  - The temperature dependence of the properties of unitary currents in cultured rat
      ventricular myocytes has been studied. Currents flowing through an ATP-dependent
      K+ channel were recorded from inside-out patches with the bath temperature varied
      from 10 degrees to 30 degrees C. The channel conductance was 56 pS at room
      temperature (22 degrees C), and the amplitudes of unitary currents and the
      channel conductance exhibited a relatively weak (Q10 from 1.4 to 1.6) dependence
      on temperature. The temperature dependence of channel mean open times was
      biphasic with the low temperature (10-20 degrees C) range showing a relatively
      stronger temperature dependence (Q10 of 2.3) than the high temperature (20-30
      degrees C) range (Q10 of 1.6). The activation energies for the two regions were
      determined from an Arrhenius plot with the activation energy, corresponding to
      the lower temperature range, near 16 kcal/mol. Thermodynamic analysis, using
      transition rate theory, indicated that the formation of a transition state prior
      to channel closure to be associated with a positive entropy component for the
      high Q10 region.

PMID- 8298032
TI  - Confined lateral diffusion of membrane receptors as studied by single particle
      tracking (nanovid microscopy). Effects of calcium-induced differentiation in
      cultured epithelial cells.
AB  - The movements of E-cadherin, epidermal growth factor receptor, and transferrin
      receptor in the plasma membrane of a cultured mouse keratinocyte cell line were
      studied using both single particle tracking (SPT; nanovid microscopy) and
      fluorescence photobleaching recovery (FPR). In the SPT technique, the receptor
      molecules are labeled with 40 nm-phi colloidal gold particles, and their
      movements are followed by video-enhanced differential interference contrast
      microscopy at a temporal resolution of 33 ms and at a nanometer-level spatial
      precision. The trajectories of the receptor molecules obtained by SPT were
      analyzed by developing a method that is based on the plot of the mean-square
      displacement against time. Four characteristic types of motion were observed: (a)
      stationary mode, in which the microscopic diffusion coefficient is less than 4.6
      x 10(-12) cm2/s; (b) simple Brownian diffusion mode; (c) directed diffusion mode,
      in which unidirectional movements are superimposed on random motion; and (d)
      confined diffusion mode, in which particles undergoing Brownian diffusion
      (microscopic diffusion coefficient between 4.6 x 10(-12) and 1 x 10(-9) cm2/s)
      are confined within a limited area, probably by the membrane-associated
      cytoskeleton network. Comparison of these data obtained by SPT with those
      obtained by FPR suggests that the plasma membrane is compartmentalized into many
      small domains 300-600 nm in diameter (0.04-0.24 microns2 in area), in which
      receptor molecules are confined in the time scale of 3-30 s, and that the long
      range diffusion observed by FPR can occur by successive movements of the
      receptors to adjacent compartments. Calcium-induced differentiation decreases the
      sum of the percentages of molecules in the directed diffusion and the stationary
      modes outside of the cell-cell contact regions on the cell surface (which is
      proposed to be the percentage of E-cadherin bound to the cytoskeleton/membrane
      skeleton), from approximately 60% to 8% (low- and high-calcium mediums,
      respectively).

PMID- 8298033
TI  - Influence of the local anesthetic tetracaine on the phase behavior and the
      thermodynamic properties of phospholipid bilayers.
AB  - We investigated the influence of the local anesthetic tetracaine on the
      thermodynamic properties and the temperature- and pressure-dependent phase
      behavior of the model biomembrane 1,2-dimyristoyl-sn-glycero-3-phosphocholine by
      using volumetric measurements at temperatures ranging from 0 degrees to 40
      degrees C and at pressures from ambient up to 1000 bar. The pVT measurements were
      complemented by temperature-dependent differential scanning calorimetric
      measurements. Information about the influence of different concentrations of the
      local anesthetic on the thermodynamic changes accompanying the lipid phase
      transitions, and on the thermal expansion coefficient, the isothermal
      compressibility, and the volume fluctuations of the lipids in their different
      phases, could be obtained from these experiments. The incorporation of tetracaine
      leads to an overall disordering of the membrane, as can be inferred from the
      depression of the main transition temperature and the reduction of the volume
      change at the main lipid phase transition. The expansion coefficient alpha p and
      the isothermal compressibility chi T of the lipid bilayer are enhanced by the
      addition of tetracaine and strongly enhanced values of alpha p and chi T, and the
      lipid volume fluctuations are found in the direct neighborhood of the main phase
      transition region. As tetracaine can be viewed as a model system for amphiphilic
      molecules, these results also provide insight into the general understanding of
      the physicochemical action of amphiphilic molecules on membranes. The
      experimental results are compared with recent theoretical predictions for the
      phase behavior of anesthetic-lipid systems, and the biological relevance of this
      study is discussed.

PMID- 8298034
TI  - Model for receptor-controlled cytosolic calcium oscillations and for external
      influences on the signal pathway.
AB  - The external stimulation of many cells by a hormone, for example, often leads to
      an oscillating cytosolic calcium concentration. This periodic behavior is now
      designated the cytosolic calcium oscillator. A theoretical model is presented
      that describes this behavior on the basis of inositol(1,4,5)trisphosphate-induced
      calcium oscillations. In contrast to other models only a single positive feedback
      loop is taken into account to obtain oscillations. The model includes important
      innovations compared to other approaches. It includes the contribution of
      extracellular calcium and its modification after the stimulation of the cell.
      Furthermore, the signal pathway that leads to cytosolic calcium oscillations is
      described in more detail than in other models. This enables investigations on the
      influence of additional parameters like external electromagnetic fields on the
      signal transduction pathway. The model and the calculations are based on the
      theory of nonlinear self-sustained oscillators.

PMID- 8298035
TI  - Modulated excitation of singly ligated carboxyhemoglobin.
AB  - We have extended the method of modulated excitation, a small perturbation kinetic
      method, to study ligand binding and conformational change of hemoglobin tetramers
      with a single ligand bound. To restrict the excitation to the first ligand, only
      1% of the hemes have bound CO, and the remainder are kept unliganded. A detailed
      theory is presented which agrees well with the experimental observations. This
      method of observing ligand recombination also provides a novel and simple method
      for determination of hemoglobin concentration. Additional relaxation processes
      are also observed. By fitting independently determined spectra to the spectra
      associated with the relaxations, these processes are assigned as thermal
      excitation and thermally driven protonation/deprotonation reactions. These added
      relaxations arise from the deoxy-Hb portion of the samples, and demonstrate that
      modulated excitation can be used effectively for temperature perturbation in the
      absence of photodissociation. The spectra observed are not well described by the
      spectra of allosteric change, however, and we conclude that there is no
      significant mixing of quaternary states at the first ligation step. In an
      appendix we present a derivation of the particular features seen in thermally
      modulated protonation reactions.

PMID- 8298036
TI  - Simulated formation of polymer domains in sickle hemoglobin.
AB  - Using experimentally observed processes of linear growth, heterogeneous
      nucleation, and polymer bending, with no additional assumptions, we have been
      able to model the two-dimensional formation of polymer domains by sickle
      hemoglobin. The domains begin with twofold symmetry and proceed toward closure
      into spherulites at a constant rate. Relationships derived from the simulations
      presented and the requirements of scaling result in simple expressions for the
      sensitivity of the closure times to the model input parameters and allow the
      results to be extended to regions not actually simulated. For concentrations
      above approximately 25 g/dl, closure times are longer than the time required for
      the conclusion of the polymerization reaction, and thus incomplete spherulites
      will be the dominant geometry at high concentrations. Moreover, spherulites are
      not predicted to form in times less than a few seconds, implying that spherulites
      will not form during the transit of erythrocytes through the capillaries. Polymer
      polymer exclusion, surface nucleation, and monomer exhaustion were also explored
      and found to have only weak effects on the results.

PMID- 8298037
TI  - Passive mechanical behavior of human neutrophils: power-law fluid.
AB  - The mechanical behavior of the neutrophil plays an important role in both the
      microcirculation and the immune system. Several laboratories in the past have
      developed mechanical models to describe different aspects of neutrophil
      deformability. In this study, the passive mechanical properties of normal human
      neutrophils have been further characterized. The cellular mechanical properties
      were assessed by single cell micropipette aspiration at fixed aspiration
      pressures. A numerical simulation was developed to interpret the experiments in
      terms of cell mechanical properties based on the Newtonian liquid drop model
      (Yeung and Evans, Biophys. J., 56: 139-149, 1989). The cytoplasmic viscosity was
      determined as a function of the ratio of the initial cell size to the pipette
      radius, the cortical tension, aspiration pressure, and the whole cell aspiration
      time. The cortical tension of passive neutrophils was measured to be about 2.7 x
      10(-5) N/m. The apparent viscosity of neutrophil cytoplasm was found to depend on
      aspiration pressure, and ranged from approximately 500 Pa.s at an aspiration
      pressure of 98 Pa (1.0 cm H2O) to approximately 50 Pa.s at 882 Pa (9.0 cm H2O)
      when tested with a 4.0-micron pipette. These data provide the first documentation
      that the neutrophil cytoplasm exhibits non-Newtonian behavior. To further
      characterize the non-Newtonian behavior of human neutrophils, a mean shear rate
      gamma m was estimated based on the numerical simulation. The apparent cytoplasmic
      viscosity appears to decrease as the mean shear rate increases. The dependence of
      cytoplasmic viscosity on the mean shear rate can be approximated as a power-law
      relationship described by mu = mu c(gamma m/gamma c)-b, where mu is the
      cytoplasmic viscosity, gamma m is the mean shear rate, mu c is the characteristic
      viscosity at characteristic shear rate gamma c, and b is a material coefficient.
      When gamma c was set to 1 s-1, the material coefficients for passive neutrophils
      were determined to be mu c = 130 +/- 23 Pa.s and b = 0.52 +/- 0.09 for normal
      neutrophils. The power-law approximation has a remarkable ability to reconcile
      discrepancies among published values of the cytoplasmic viscosity measured using
      different techniques, even though these values differ by nearly two orders of
      magnitude. Thus, the power-law fluid model is a promising candidate for
      describing the passive mechanical behavior of human neutrophils in large
      deformation. It can also account for some discrepancies between cellular behavior
      in single-cell micromechanical experiments and predictions based on the
      assumption that the cytoplasm is a simple Newtonian fluid.

PMID- 8298038
TI  - Conduction properties of the cloned Shaker K+ channel.
AB  - The conduction properties of the cloned Shaker K+ channel were studied using
      electrophysiological techniques. Single channel conductance increases in a
      sublinear manner with symmetric increases in K+ activity, reaching saturation by
      0.6 M K+. The Shaker K+ channel is highly selective among monovalent cations;
      under bi-ionic conditions, its selectivity sequence is K+ > Rb+ > NH+4 > Cs+ >
      Na+, whereas, by relative conductance in symmetric solutions, it is K+ > NH+4 >
      Rb+ > Cs+. In Cs+ solutions, single channel currents were too small to be
      measured directly, so nonstationary fluctuation analysis was used to determine
      the unitary Cs+ conductance. The single channel conductance displays an anomalous
      molefraction effect in symmetric mixtures of K+ and NH+4, suggesting that the
      conducting pore is occupied by multiple ions simultaneously.

PMID- 8298039
TI  - Energetics of intermediates in membrane fusion: comparison of stalk and inverted
      micellar intermediate mechanisms.
AB  - To understand the mechanism of membrane fusion, we have to infer the sequence of
      structural transformations that occurs during the process. Here, it is shown how
      one can estimate the lipid composition-dependent free energies of intermediate
      structures of different geometries. One can then infer which fusion mechanism is
      the best explanation of observed behavior in different systems by selecting the
      mechanism that requires the least energy. The treatment involves no adjustable
      parameters. It includes contributions to the intermediate energy resulting from
      the presence of hydrophobic interstices within structures formed between apposed
      bilayers. Results of these calculations show that a modified form of the stalk
      mechanism proposed by others is a likely fusion mechanism in a wide range of
      lipid compositions, but a mechanism based on inverted micellar intermediates
      (IMIs) is not. This should be true even in the vicinity of the lamellar/inverted
      hexagonal phase transition, where IMI formation would be most facile. Another
      prediction of the calculations is that traces of apolar lipids (e.g., long-chain
      alkanes) in membranes should have a substantial influence on fusion rates in
      general. The same theoretical methods can be used to generate and refine
      mechanisms for protein-mediated fusion.

PMID- 8298040
TI  - Passive tension and stiffness of vertebrate skeletal and insect flight muscles:
      the contribution of weak cross-bridges and elastic filaments.
AB  - Tension and dynamic stiffness of passive rabbit psoas, rabbit semitendinosus, and
      waterbug indirect flight muscles were investigated to study the contribution of
      weak-binding cross-bridges and elastic filaments (titin and minititin) to the
      passive mechanical behavior of these muscles. Experimentally, a functional
      dissection of the relative contribution of actomyosin cross-bridges and titin and
      minititin was achieved by 1) comparing mechanically skinned muscle fibers before
      and after selective removal of actin filaments with a noncalcium-requiring
      gelsolin fragment (FX-45), and 2) studying passive tension and stiffness as a
      function of sarcomere length, ionic strength, temperature, and the inhibitory
      effect of a carboxyl-terminal fragment of smooth muscle caldesmon. Our data show
      that weak bridges exist in both rabbit skeletal muscle and insect flight muscle
      at physiological ionic strength and room temperature. In rabbit psoas fibers,
      weak bridge stiffness appears to vary with both thin-thick filament overlap and
      with the magnitude of passive tension. Plots of passive tension versus passive
      stiffness are multiphasic and strikingly similar for these three muscles of
      distinct sarcomere proportions and elastic proteins. The tension-stiffness plot
      appears to be a powerful tool in discerning changes in the mechanical behavior of
      the elastic filaments. The stress-strain and stiffness-strain curves of all three
      muscles can be merged into one, by normalizing strain rate and strain amplitude
      of the extensible segment of titin and minititin, further supporting the
      segmental extension model of resting tension development.

PMID- 8298041
TI  - Influence of surface chemistry on the structural organization of monomolecular
      protein layers adsorbed to functionalized aqueous interfaces.
AB  - The molecular organization of streptavidin (SA) bound to aqueous surface
      monolayers of biotin-functionalized lipids and binary lipid mixtures has been
      investigated with neutron reflectivity and electron and fluorescence microscopy.
      The substitution of deuterons (2H) for protons (1H), both in subphase water
      molecules and in the alkyl chains of the lipid surface monolayer, was utilized to
      determine the interface structure on the molecular length scale. In all cases
      studied, the protein forms monomolecular layers underneath the interface with
      thickness values of approximately 40 A. A systematic dependence of the structural
      properties of such self-assembled SA monolayers on the surface chemistry was
      observed: the lateral protein density depends on the length of the spacer
      connecting the biotin moiety and its hydrophobic anchor. The hydration of the
      lipid head groups in the protein-bound state depends on the dipole moment density
      at the interface.

PMID- 8298042
TI  - Solution 1H nuclear magnetic resonance determination of the distal pocket
      structure of cyanomet complexes of genetically engineered sperm whale myoglobin
      His64 (E7)-->Val, Thr67 (E10)-->Arg. The role of distal hydrogen bonding by Arg67
      (E10) in modulating ligand tilt.
AB  - Sequence-specific 2D methodology has been used to assign the 1H NMR signals for
      all active site residues in the paramagnetic cyano-met complexes of sperm whale
      synthetic double mutant His64[E7]-->Val/Thr67[E10]-->Arg (VR-met-MbCN) and triple
      mutant His64[E7]-->Val/Thr67[E10]-->Arg/Arg45[CD3]-->Asn (VRN-metMbCN). The
      resulting dipolar shifts for noncoordinated proximal side residues were used to
      quantitatively determine the orientation of the paramagnetic susceptibility
      tensor in the molecular framework for the two mutants, which were found
      indistinguishable but distinct from those of both wild-type and the His64[E7]-
      >Val single point mutant (V-metMbCN). The observed dipolar shifts for the E helix
      backbone protons and Phe43[CD1], together with steady-state nuclear Overhauser
      effect between the E helix and the heme, were analyzed to show that both the E
      helix and Phe43[CD1] move slightly closer to the iron to minimize the vacancy
      resulting from the His64[E7]-->Val substitution, as found in V-metMbCN
      (Rajarathnam, K., J. Qin, G.N. LaMar, M. L. Chiu, and S. G. Sligar. 1993.
      Biochemistry. 32:5670-5680). The dipolar shifts of the mutated Val64[E7] and
      Arg67[E10] allow the determination of their orientations relative to the heme,
      and the latter residue is shown to insert into the pocket and provide a hydrogen
      bond to the coordinated ligand, as found in the naturally occurring ValE7/ArgE10
      genetic variant, Aplysia limacina Mb. The oxy-complex of both A. limacina Mb and
      VR-Mb, VRN-Mb have been proposed to be stabilized by this hydrogen bonding
      interaction (Travaglini Allocatelli, C. et al. 1993. Biochemistry. 32:6041-6049).
      The magnitude of the tilt of the major magnetic axes from the heme normal in VR
      metMbCN and VRN-metMbCN, which is related to the tilt of the ligand, is the same
      as in wild-type or V-metMbCN, but the direction of tilt is altered from that in V
      metMbCN. It is concluded that the change in the direction of the ligand tilt in
      both the double and triple mutants, as compared to WT metMbCN and V-metMbCN
      single mutant, is due to the attractive hydrogen-bonding between ArgE10 and the
      bound cyanide.

PMID- 8298043
TI  - Relationship between receptor/ligand binding affinity and adhesion strength.
AB  - Receptor-mediated cell adhesion is a central phenomenon in many physiological and
      biotechnological processes. Mechanical strength of adhesion is generally presumed
      to be related to chemical affinity of receptor/ligand bonds, but no experimental
      study has been previously directed toward this issue. Here we investigate the
      dependence of receptor/ligand adhesion strength on bond affinity using a radial
      fluid flow chamber assay to measure the force needed to detach polystyrene beads
      covalently coated with immunoglobulin G from glass surfaces covalently coated
      with protein A. A spectrum of animal species sources for immunoglobulin G permits
      examination of three decades of protein A/immunoglobulin G binding affinity. Our
      results for this model system demonstrate that adhesion strength varies with the
      logarithm of the binding affinity, consistent with a prediction from the
      theoretical model by Dembo et al. (Dembo, M., D.C. Torney, K. Saxman, and D.
      Hammer. 1988. Proc. R. Soc. Lond. Ser. B 234:55-83).

PMID- 8298044
TI  - Torque generated by the flagellar motor of Escherichia coli.
AB  - Cells of the bacterium Escherichia coli were tethered and spun in a high
      frequency rotating electric field at a series of discrete field strengths. This
      was done first at low field strengths, then at field strengths generating speeds
      high enough to disrupt motor function, and finally at low field strengths.
      Comparison of the initial and final speed versus applied-torque plots yielded
      relative motor torque. For backward rotation, motor torque rose steeply at speeds
      close to zero, peaking, on average, at about 2.2 times the stall torque. For
      forward rotation, motor torque remained approximately constant up to speeds of
      about 60% of the zero-torque speed. Then the torque dropped linearly with speed,
      crossed zero, and reached a minimum, on average, at about -1.7 times the stall
      torque. The zero-torque speed increased with temperature (about 90 Hz at 11
      degrees C, 140 Hz at 16 degrees C, and 290 Hz at 23 degrees C), while other
      parameters remained approximately constant. Sometimes the motor slipped at either
      extreme (delivered constant torque over a range of speeds), but eventually it
      broke. Similar results were obtained whether motors broke catastrophically
      (suddenly and completely) or progressively or were de-energized by brief
      treatment with an uncoupler. These results are consistent with a tightly coupled
      ratchet mechanism, provided that elastic deformation of force-generating elements
      is limited by a stop and that mechanical components yield at high applied
      torques.

PMID- 8298045
TI  - Harmonics of outer hair cell motility.
AB  - The voltage-dependent mechanical activity of outer hair cells (OHC) from the
      organ of Corti is considered responsible for the peripheral auditory system's
      enhanced ability to detect and analyze sound. Nonlinear processes within the
      inner ear are presumed to be characteristic of this enhancement process. Harmonic
      distortion in the OHC mechanical response was analyzed under whole-cell voltage
      clamp. It is shown that the OHC produces DC, fundamental and second harmonic
      length changes in response to sinusoidal transmembrane voltage stimulation.
      Mechanical second harmonic distortion decreases with frequency, whereas the
      predicted transmembrane second harmonic voltage increases with frequency.
      Furthermore, the phase of the second harmonic distortion does not correspond to
      the phase of the predicted transmembrane voltage. In contradistinction, it has
      been previously shown (Santos-Sacchi, J. 1992. Neuroscience. 12:1906-1916) that
      fundamental voltage and evoked mechanical responses share magnitude and phase
      characteristics. OHC length changes are modeled as resulting from voltage
      dependent cell surface area changes. The model suggests that the observed
      harmonic responses in the mechanical response are consistent with the
      nonlinearity of the voltage-to-length change (V-delta L) function. While these
      conclusions hold for the data obtained with the present voltage clamp protocol
      and help to understand the mechanism of OHC motility, modeling the
      electromechanical system of the OHC in the in vivo state indicates that the
      mechanical nonlinearity of the OHC contributes minimally to mechanical
      distortion. That is, in vivo, at moderate sound pressure levels and below, the
      dominant factor which contributes to nonlinearities of the OHC mechanical
      response resides within the nonlinear, voltage-generating, stereociliar
      transduction process.

PMID- 8298046
TI  - Mapping the distribution of the outer hair cell motility voltage sensor by
      electrical amputation.
AB  - The outer hair cell (OHC) possesses a nonlinear charge movement whose
      characteristics indicate that it represents the voltage sensor responsible for
      OHC mechanical activity. OHC mechanical activity is known to exist along a
      restricted extent of the cell's length. We have used a simultaneous partitioning
      microchamber and whole cell voltage clamp technique to electrically isolate
      sections of the OHC membrane and find that the nonlinear charge movement is also
      restricted along the cell's length. Apical and basal portions of the OHC are
      devoid of voltage sensors, corresponding to regions of the cell where the
      subsurface cisternae and/or the mechanical responses are absent. We conclude that
      the physical domain of the motility voltage sensor corresponds to that of the
      mechanical effector and speculate that sensor and effector reside within one
      intra membranous molecular species, perhaps an evolved nonconducting or poorly
      conducting voltage-dependent ion channel.

PMID- 8298047
TI  - Lipid clustering in bilayers detected by the fluorescence kinetics and anisotropy
      of trans-parinaric acid.
AB  - Fluid heterogeneity in lipid bilayers and shows a simple and useful method to
      quantify this heterogeneity. Taking advantage of the maximum entropy method, we
      have resolved the probe fluorescence lifetime distributions in homogeneous
      solutions and in single and two-component lipid bilayers at different
      temperatures. A precise description of the emission kinetics was obtained as a
      function of viscosity in the homogeneous solution and as a function of the phase
      composition (gel/fluid) in the lipid bilayers. These data show, unambiguously,
      that the same distribution pattern, with two well resolved lifetime classes, is
      observed both in pure solvents and in fluid bilayers. This distribution is
      modified during the thermotropic phase transition, with the appearance of a long
      lifetime component. The anisotropy experiments confirm that the amplitude of this
      component is proportional to the fraction of probe located in the gel phase. From
      this fraction we have quantified the amount of gel phase in the binary bilayer
      system dimyristoyl phosphatidylcholine/dipalmitoyl phosphatidylcholine and
      determined the thermotropic phase diagram of the mixture. This phase diagram
      agrees well with that calculated assuming ideal mixing of the lipids (Marbrey,
      S., and J.M. Sturtevant. 1976. Proc. Natl. Acad. Sci. USA. 73:862-3866).

PMID- 8298048
TI  - Pressure effects on the physical properties of lipid bilayers detected by trans
      parinaric acid fluorescence decay.
AB  - The effects of hydrostatic pressure on the physical properties of large
      unilamellar vesicles of single lipids dipalmitoyl phosphatidylcholine (DPPC) and
      dimyristoyl phosphatidylcholine (DMPC) and lipid mixtures of DMPC/DPPC have been
      studied from time-resolved fluorescence of trans-parinaric acid. Additional
      experiments were carried out using diphenylhexatriene to compare the results
      extracted from both probes. Fluorescence decays were analyzed by the maximum
      entropy method. Pressure does not influence the fluorescence lifetime
      distribution of trans-parinaric acid in isotropic solvents. However, in
      pressurized lipid bilayers an abrupt change was observed in the lifetime
      distribution which was associated with the isothermal pressure-induced phase
      transition. The pressure to temperature equivalence values, dT/dP, determined
      from the midpoint of the phase transitions, were 24 and 14.5 degrees C kbar-1 for
      DMPC and POPC, respectively. Relatively moderate pressures of about 500 bar
      shifted the DMPC/DPPC phase diagram 11.5 degrees C to higher temperatures. The
      effects of pressure on the structural properties of these lipid vesicles were
      investigated from the anisotropy decays of both probes. Order parameters for all
      systems increased with pressure. In the gel phase of POPC the order parameter was
      smaller than that obtained in the same phase of saturated phospholipids,
      suggesting that an efficient packing of the POPC hydrocarbon chains is hindered.

PMID- 8298050
TI  - Biophysical Society 38th annual meeting. New Orleans, Louisiana, 6-10 March 1994.
      Abstracts.

PMID- 8298049
TI  - Orthophosphate and the fastest component of the mechanical transient in skinned
      muscle fibers.

PMID- 8298052
TI  - Fluorescence spectroscopic studies on equilibrium dipole-relaxational dynamics of
      Na,K-ATPase.
AB  - Intramolecular dynamics in Na,K-ATPase molecules have been studied by ultraviolet
      fluorescence spectroscopic methods: determination of temperature-dependent shifts
      in steady-state spectra, site-selective red-edge effects and their temperature
      dependence, and time-resolved emission decay as a function of excitation and
      emission wavelengths. The combination of these methods allows the
      characterization of the dipolar-relaxational mobility in the environment of the
      tryptophan residues. Our results show that the mean dipolar-relaxational time is
      of the order of one nanosecond at room temperature. This is much faster than what
      is usually observed in globular proteins. The fast dynamics of the protein
      dipoles are rapid enough so that the dipoles are in dielectric equilibrium during
      the slower ion transfer processes; this may have important functional
      consequences.

PMID- 8298051
TI  - Compact thermally-denatured state of a staphylococcal nuclease mutant from
      resonance energy transfer measurements.
AB  - Thermal denaturation of a staphylococcal nuclease mutant K78C, where lysine 78 is
      replaced by cysteine, was studied by circular dichroism (CD) and resonance energy
      transfer. CD spectra suggest that residual structures remain in the denatured
      state. Steady-state energy transfer from intrinsic tyrosines to a single and
      intrinsic tryptophan was measured at different temperatures. In the thermally
      denatured state of K78C, there is still a substantial degree of energy transfer
      from tyrosine(s) to tryptophan, indicating residual structures in the denatured
      state. The cysteine residue in mutant K78C was labeled with a cysteine specific
      probe IAEDANS. Fluorescence decays of the tryptophan were measured to estimate
      distance distributions between Trp 140 and IAEDANS at position 78. Measurements
      were done as a function of temperature from 4 degrees C (native) to 65 degrees C
      (denatured) both with and without Ca2+ and inhibitor pdTp. Below 30 degrees C,
      the apparent distance distribution of both the ligand-free nuclease and the
      enzyme with bound pdTp can be adequately described by a Gaussian model. Above 40
      degrees C, where the ligand-free nuclease but not the ternary complex begins to
      denature, two different populations are required to fit the data both with and
      without pdTp. One population has a compact structure and the other has an
      expanded structure. As temperature rises, the population of the expanded
      structure increases. At the highest temperature, the non-native compact structure
      is still the major form (60 to 70%). The overall thermally-denatured states of
      staphylococcal nuclease mutant K78C in the absence and presence of ligands are
      thus compact and heterogeneous.

PMID- 8298053
TI  - Lumazine protein and the excitation mechanism in bacterial bioluminescence.
AB  - The spectral properties of lumazine protein and mixtures with the intermediates
      of the bacterial luciferase reaction, are reviewed. Measurements of fluorescence
      dynamics in particular have been employed with the aim of elucidating the
      mechanism by which lumazine protein functions in the bioluminescence of the
      bacteria of the type Photobacterium. The reaction of bacterial luciferase with
      its substrates produces bioluminescence emission with a spectral maximum at 496
      nm. This spectrum is the same as the fluorescence of a luciferase flavin
      intermediate in the reaction, called the Fluorescent Transient. When lumazine
      protein is also present in the reaction; however, the bioluminescence emission
      now corresponds to the fluorescence of lumazine protein, which has a maximum at
      475 nm. From measurements of the decay of fluorescence anisotropy of lumazine
      protein alone and in mixtures with the luciferase fluorescent transient, it is
      shown that a protein-protein complex is formed and that there is rapid energy
      transfer between the flavin on the luciferase and the lumazine derivative bound
      to its protein. An approximate calculation estimates the rate of this energy
      transfer to be faster than 10(9) s-1, and this would account for the efficient
      transfer of excitation from the flavin on the associated luciferase in the mixed
      protein bioluminescence reaction.

PMID- 8298054
TI  - Characterization of aminoacyl-adenylates in B. subtilis tryptophanyl-tRNA
      synthetase, by the fluorescence of tryptophan analogs 5-hydroxytryptophan and 7
      azatryptophan.
AB  - The tryptophan analogs 5-hydroxytryptophan (5HW) and 7-azatryptophan (7AW) are
      capable of being biosynthetically incorporated into bacterial proteins and can be
      used as intrinsic fluorescence probes of protein structure, function and
      dynamics. A prerequisite for analog incorporation is their recognition by
      tryptophanyl-tRNA synthetase (TrpRS) and the formation of the analog
      aminoacyladenylate in the enzyme's active site. The binding of 5HW and 7AW to B.
      subtilis TrpRS and the stability of the corresponding aminoacyladenylates of 5HW
      and 7AW were examined using their unique spectroscopic properties. The adenylate
      of 7AW in the active site of TrpRS exhibited intense fluorescence with a 10.5 ns
      fluorescence decay time. Enzyme-bound 7AW-adenylate was a long-lived intermediate
      with a half-life of over 9 hours. Enzyme-bound 5HW-adenylate fluorescence was
      quenched compared to that of 5HW in solution. The 5HW-adenylate/TrpRS complex was
      much less stable than that of 7AW, with a half-life of 33 minutes. Rapid
      hydrolysis of the 5HW-adenylate may explain the apparent proofreading observed
      which prohibits 5HW incorporation into proteins in the presence of tryptophan.
      Hydrolysis of the adenylates of both analogs restored the fluorescence parameters
      towards those of the analogs in solution. Neither 1-methyltryptophan nor 5
      methoxytryptophan were capable of forming long-lived aminoacyladenylate
      intermediates in TrpRS. This study provides perspectives on the usefulness of 5HW
      and 7AW as intrinsic fluorescence probes of protein structure. The enhanced
      fluorescence of 7AW suggests its location in a buried hydrophobic environment in
      the protein. Exposure to water results in significant fluorescence quenching.
      These studies clearly demonstrate the utility of Trp analogs for the elucidation
      of molecular details of protein structure and dynamics.

PMID- 8298055
TI  - Molten globule monomers in human superoxide dismutase.
AB  - The time-resolved fluorescence decay and anisotropy of Cu/Zn human superoxide
      dismutase (HSOD) were studied as a function of temperature and denaturant
      concentration. In addition, circular dichroism (CD) measurements were performed
      on HSOD as a function of denaturant concentration in the amide and aromatic
      regions. The time-resolved fluorescence decay results reveal the existence of
      structural microheterogeneity in HSOD. Furthermore, CD measurements and a global
      analysis decomposition of the time-resolved fluorescence decay over denaturant
      concentration shows the presence of an intermediate in the unfolding of HSOD by
      guanidinium hydrochloride. Considering our previous measurements of partially
      denatured HSOD as a function of protein concentration (Mei et al., Biochemistry
      31 (1992) 7224-7230), our results strongly suggest that the unfolding
      intermediate is a monomer that displays a molten globule state.

PMID- 8298056
TI  - The interaction of pyrene labeled diacylglycerol with protein kinase C in mixed
      micelles.
AB  - The binding of protein kinase C (PKC) to pyrene-labeled diacylglycerol (pDG) has
      been studied in a mixed micellar system by monitoring resonance energy transfer
      from excited tryptophans to pyrene with time-correlated single photon counting.
      The average lifetime of the excited state of the tryptophans in PKC showed a
      clear dependence on the mole percentage pDG in micelles in contrast with pyrene
      labeled phosphatidylcholine (pPC). The binding data has been analyzed to a simple
      model which encompasses the size of the micelles and the binding constant of the
      pDG-PKC complex. From our data, though, these quantities cannot be determined
      independently. If we have no size information on the micelles we can determine a
      lower boundary of this quantity compatible with the data. When the micellar size
      is known, a binding constant for the DG-PKC complex can be extracted. The
      presented analytical approach can be applied to other systems in which lipid
      protein interactions must be quantified.

PMID- 8298057
TI  - Fluorescence quenching by metal ions in lipid bilayers.
AB  - Fluorescence quenching of perylene by Co2+ and Ni2+ ions has been investigated
      both below and above the phase transition temperature in small unilamellar DPPC
      vesicles. Classic Forster type energy transfer was observed for perylene quenched
      by Co2+ ions below the phase transition when the effects of donor-donor energy
      transfer are taken into account. In the liquid crystalline phase a simple
      diffusion theory incorporating energy transfer was found to model the system
      well. For quenching by Ni2+ ions both above and below the phase transition
      temperature in lipid bilayers and in glycerol the data did not follow classic
      Forster type energy transfer but indicated that an additional quenching mechanism
      was present. A mechanism other than Forster behaviour was also observed for the
      quenching by Cr3+ ions in glycerol.

PMID- 8298058
TI  - Fluorescence decay of DPH in lipid membranes: influence of the external
      refractive index.
AB  - The radiative decay rate of a fluorescent probe in an optically thin layer is
      known to depend on the orientation of the probe and on the refractive indices
      inside and outside the layer (W. Lukosz, Phys. Rev. B 22 (1980) 3030).
      Fluorescent probes in phospholipid bilayer membranes approximate such a system.
      The natural lifetime is expected to vary with the refractive index of the medium
      surrounding the bilayer. The lifetime variation with the refractive index depends
      on the orientation of the fluorescent probe. This can be used to retrieve the
      second-rank orientational order parameter, <P2>. The fluorescence decay of all
      trans 1,6-diphenyl-1,3,5-hexatriene in L-alpha-dipalmitoyl-phosphatidylcholine
      large unilamellar vesicles (LUVs) was measured at a temperature well below that
      of the phase transition. The refractive index of the medium was varied by
      addition of glycerol or sucrose. The observed change of decay time with the
      refractive index followed the theoretical prediction. The value of the order
      parameter, <P2>, recovered is significantly lower than that obtained from
      fluorescence polarization data. Possible reasons for this disagreement are
      discussed.

PMID- 8298059
TI  - Use of laser flash photolysis time-resolved spectrophotometry to investigate
      interprotein and intraprotein electron transfer mechanisms.
AB  - A description is given of the methodology developed in our laboratory for the
      application of laser flash photolysis to the elucidation of the kinetics and
      mechanism of electron transfer processes which occur intermolecularly between two
      protein molecules within a collisional complex, or intramolecularly between two
      redox centers within a single multisubunit or multidomain protein. This involves
      the use of flavin analogs, excited to their lowest triplet state by a laser
      flash, to initiate electron transfer, either by oxidation of a sacrificial donor
      followed by redox protein reduction via the flavin semiquinone, or by direct
      oxidation of a reduced redox protein by the flavin triplet. Time-resolved
      spectrophotometry is used to follow the course of the sequence of electron
      transfer events initiated by the laser flash. The application of this methodology
      to the following systems is described: cytochrome c/cytochrome c peroxidase;
      ferredoxin/ferredoxin NADP+ reductase; cytochrome c/plastocyanin; flavocytochrome
      b2; and sulfite oxidase.

PMID- 8298060
TI  - Detection of intermediate protein conformations by room temperature tryptophan
      phosphorescence spectroscopy during denaturation of Escherichia coli alkaline
      phosphatase.
AB  - The reversible denaturation of Escherichia coli alkaline phosphatase (AP) was
      followed by monitoring changes in enzymatic activity as well as by measurements
      of the time-resolved room temperature phosphorescence from Trp 109. It is well
      known that the denaturants, ethylene diamine tetraacetic acid (EDTA), acid and
      guanidine hydrochloride (GdnHCl) inactive AP by different mechanisms as reflected
      by differences in the time dependence of inactivation. However, further
      information about structural changes that result during inactivation is obtained
      by measurement of the phosphorescence intensity and radiative decay rate. Time
      resolved tryptophan phosphorescence is exquisitely sensitive to changes in the
      local environment of the emitting residue, unlike the steady state
      phosphorescence intensity which is a composite of both the lifetime and
      concentration of the emitting protein species. The results show that while
      inactivation in EDTA proceeds by loss of the zinc ion as expected, denaturation
      in acid or GdnHCl produces a heterogeneous population of AP molecules, detected
      by a distribution analysis of the phosphorescence lifetime, which may reflect
      multiple pathways to the final unfolded state. Time-resolved phosphorescence also
      demonstrates the existence of an enzymatically active but structurally less rigid
      intermediate state during unfolding. As the rigidity decreases, the
      susceptibility to further denaturation decreases at lower pH but increases with
      GdnHCl concentration. The experiments provide new insight into the mechanism of
      denaturation of AP and demonstrate the sensitivity of time-resolved room
      temperature phosphorescence to the structural details of intermediate states
      produced during unfolding of proteins.

PMID- 8298061
TI  - Metabolism of the failing heart.
AB  - Our understanding of the pathogenesis and therapy of heart failure has evolved
      through three paradigms. Organ physiology, the first paradigm, focused therapy of
      heart failure on salt and water retention and vasoconstriction, which represent
      major circulatory responses to, cardiac pumping. The second paradigm of cell
      biochemistry led to the development of powerful inotropic agents designed to
      increase myocardial contractility. The third paradigm, gene expression (molecular
      biology), describes regulatory mechanisms that are both primitive and complex; in
      the setting of heart failure, this paradigm focuses on the roles of altered
      myocardial cell growth and composition in explaining the accelerated
      deterioration of the hypertrophied, failing heart. This review focuses on one
      aspect of the second paradigm: factors that contribute to a state of energy
      starvation and the resulting functional consequences in the failing heart.

PMID- 8298062
TI  - Free radical effects on myocardial membrane microviscosity.
AB  - Previous studies have shown that myocardial membranes, isolated from ischemic
      myocardial tissue, showed marked changes in microviscosity. To evaluate the
      contribution of free radical production and concomitant lipid peroxidation to
      these changes in microviscosity, the in vitro effects of two radical producing
      systems (H2O2/FeCl2 and xanthine oxidase/hypoxanthine/FeCl3) were investigated
      separately on the microviscosity of sarcolemmal, mitochondrial and sarcoplasmic
      reticulum membranes. In all three membranes both these free radical producing
      systems caused formation of malondialdehyde as quantitated by the thiobarbituric
      acid test. The sensitivity of the membranes to free radical damage differed: the
      sarcolemma was more sensitive to H2O2 damage, while mitochondrial malondialdehyde
      production was highest with xanthine oxidase. H2O2/FeCl2 caused a reduction in
      microviscosity (i.e. increased fluidity) of all three membranes, whereas the
      xanthine oxidase system increased mitochondrial and sarcolemmal microviscosity
      and reduced that of the sarcoplasmic reticulum. The similarity between ischemia
      induced membrane microviscosity changes and those induced in vitro by xanthine
      oxidase, indicate a possible causal role for superoxide and hydroxyl free
      radicals produced during ischemia.

PMID- 8298063
TI  - Rheological features of erythrocytes in acute myocardial infarction.
AB  - There is evidence that oxidative insult plays a role in the development of acute
      myocardial infarction. Significance has also been attributed to changes in
      viscosity of the blood and in the deformability and aggregation of erythrocytes
      affecting their rheological behavior. In a group of patients with myocardial
      infarction we found a decreased erythrocyte filtration and an increased blood
      viscosity with no significant change in plasma viscosity. These changes were
      accompanied by alterations in the microviscosity of the erythrocyte membrane
      assessed by measuring the polarization of specific fluorescent molecules. From
      our data it is evident that there is an increase in the rigidity of the membrane
      at the lipid/protein boundary, with an associated increase in the fluidity of the
      deep lipid core of the membrane, while no changes were observed in the dynamic
      behavior of the membrane proteins. These physico-chemical perturbations in the
      membrane could be the basis for the decreased filtration of erythrocytes. We
      found, however, no evidence of lipid peroxidation in the erythrocyte membrane.

PMID- 8298064
TI  - Depressed adenosine and total purine catabolite production in the postischemic
      rat heart.
AB  - The influence of global ischemia on myocardial nucleotide catabolite production
      and contraction was studied in Langendorff-perfused rat hearts. Hearts in the
      "ischemic" group were subjected to a 25 minute period of global ischemia at 30
      minutes from the start of perfusion, and to two 30 s periods of global ischemia
      at 20 and 80 minutes of perfusion. Control hearts were subjected to three 30 s
      periods of ischemia at 20, 45 and 80 minutes of perfusion. Left ventricular
      developed pressure and concentrations of total nucleotide catabolites and
      adenosine in the coronary effluent were measured throughout. The concentration of
      nucleotide catabolites increased transiently by 2.1 +/- 0.5 microM in the control
      group and 2.2 +/- 0.8 microM in the "ischemic" group, immediately after 30 s
      ischemia at 20 minutes; while the concentration of adenosine increased
      transiently by 0.17 +/- 0.08 microM in the control group and 0.13 +/- 0.09 microM
      in the "ischemic" group. The next 30 s ischemic period in control hearts caused
      nucleotide catabolites to increase by 1.7 +/- 0.5 microM and adenosine by 0.12 +/
      0.06 microM. In the "ischemic" group, massive purine release was observed after
      25 minutes of ischemia, the release decreasing to below pre-ischemic levels after
      10 minutes of reperfusion. The increases in effluent nucleotide catabolites and
      adenosine in response to 30 s ischemia at 80 minutes were 1.4 +/- 0.4 microM and
      0.13 +/- 0.1 microM, respectively, in the control group. In contrast, in the
      "ischemic" group, nucleotide catabolites increased by only 0.3 +/- 0.2 microM and
      adenosine by 0.011 +/- 0.008 microM after 30 s ischemia at the same
      time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298065
TI  - Effects of pilsicainide on systemic hemodynamics and cardiac function of
      anesthetized dogs.
AB  - The effects of pilsicainide, propafenone and flecainide on systemic hemodynamics
      and cardiac function were compared in anesthetized open-chest dogs. Pilsicainide,
      propafenone and flecainide given intravenously at 1 and 3 mg/kg produced dose
      dependent decreases in the mean aortic pressure. The heart rate was decreased by
      pilsicainide and flecainide, but not by propafenone. The three drugs increased
      the left ventricular end-diastolic pressure and reduced the first derivative of
      left ventricular pressure and myocardial oxygen consumption. Pilsicainide
      decreased aortic, vertebral, coronary and renal blood flows in a dose-dependent
      manner at 1 and 3 mg/kg. Propafenone increased aortic and vertebral blood flows
      at 1 mg/kg and decreased coronary and renal blood flows at 3 mg/kg. Flecainide
      did not significantly change blood flow, except for an increase in the aortic
      blood flow with 3 mg/kg. The total peripheral, vertebral, coronary and renal
      vascular resistances were increased by pilsicainide, but not by flecainide.
      Propafenone decreased total peripheral and vertebral vascular resistances, but
      hardly affected the coronary and renal vascular resistances. The stroke volume
      was decreased by 1 and 3 mg/kg pilsicainide in a dose-dependent manner, and
      increased by 1 and 3 mg/kg propafenone, but not significantly changed by 1 or 3
      mg/kg flecainide. The stroke work index was decreased by 3 mg/kg pilsicainide and
      3 mg/kg flecainide. The effects of pilsicainide correlated with the changes in
      its plasma concentration with time. The results indicate that pilsicainide has a
      negative inotropic activity similar to that of propafenone and flecainide.
      Pilsicainide and flecainide show almost the same effects with a slightly
      different efficacy, while propafenone exerts different effects upon some
      cardiovascular functions.

PMID- 8298066
TI  - Metabolic analysis of latissimus dorsi coupled to a mock circulation.
AB  - A mock circulation system has been used to examine the metabolic and hemodynamic
      responses of untrained and trained latissimus dorsi muscle in a normal animal
      model. The metabolic response of untrained latissimus dorsi to differing
      stimulation regimes runs parallel to its mechanical performance. The ratio of
      power generated to oxidative capacity (a measure of metabolic efficiency) was
      maintained to a greater extent in muscle trained for 5 months subjected to
      specific fatigue tests, falling by only 20% (as opposed to 80% observed in
      untrained control muscle). This approach to studying metabolic and hemodynamic
      performance may have relevance when skeletal muscle is used for cardiac
      assistance.

PMID- 8298067
TI  - Effect of thyroid status on phosphatidylinositols in rat heart.
AB  - The incorporation of 32Pi into phosphatidylinositols and inositol trisphosphates
      was studied in Langendorff-perfused hearts from hypothyroid, euthyroid and
      hyperthyroid rats. The hearts were perfused with modified Krebs buffer containing
      [32P]orthophosphate and the degree of 32P-labeling of phosphatidylinositol,
      phosphatidylinositol 4-monophosphate, phosphatidylinositol 4,5-bisphosphate,
      inositol trisphosphates and phosphatidic acid was measured. Hyperthyroidism was
      associated with increases in rates of rise and fall of left ventricular systolic
      pressure, sarcoplasmic reticular Ca(2+)-ATPase activity and 32P-labeling of
      phosphatidylinositols, inositol trisphosphates and phosphatidic acid. These
      measurements were significantly decreased in hypothyroid hearts. The tissue
      levels of inositol 1,4,5-trisphosphate isoform were found to be significantly
      higher in hyperthyroid hearts and lower in hypothyroid hearts than in euthyroid
      ones. Examination of phosphoinositide-specific phospholipase C activity in the
      perfused hearts revealed that hyperthyroidism was associated with an increase in
      the membrane-associated enzymatic activity, assayed at physiological calcium
      concentrations, while hypothyroidism was associated with a decrease in this
      activity as compared with control hearts. These findings indicate that
      alterations in the thyroid state of the myocardium may be associated with changes
      in basal phosphoinositide turnover which may contribute to alterations in
      myocardial contraction.

PMID- 8298068
TI  - Global myocardial ischemia protects the myocardium from subsequent regional
      ischemia.
AB  - Many investigators use in vitro models of global ischemia to examine the effects
      of preconditioning, often with recovery of contractile function as the end-point.
      Such models are relevant to myocardial protection during cardiac surgery.
      However, there is still debate as to whether preconditioning preserves
      ventricular contraction secondary to limitation of infarction or by a direct
      effect on stunning. Since infarct size is the original end-point against which
      protection by preconditioning is measured, our aims were, first, to validate
      global ischemic preconditioning by measuring infarct size after subsequent
      regional ischemia and, second, to correlate limitation of infarct size with
      mechanical function. After stabilization, seven isolated buffer perfused rabbit
      hearts were subjected to 5 minutes of global "no-flow" ischemia followed by 10
      minutes of reperfusion ("global preconditioning"). Seven control hearts were
      allowed to stabilize for an additional 15 minutes at constant flow. Subsequently,
      regional ischemia was induced in both groups for 45 minutes followed by 2 hours
      of reperfusion. Left ventricular and coronary perfusion pressures were measured
      throughout. Myocardial infarct size was measured using triphenyltetrazolium
      staining and expressed as a percentage of the area at risk outlined with
      fluorescent microspheres. The ratio of infarct to risk zone was reduced from 47.6
      +/- 7.3% in control hearts to 16.4 +/- 5.4% (p = 0.005) in preconditioned hearts,
      confirming the efficacy of global preconditioning. In addition, preconditioning
      led to a better preservation of systolic function, which correlated significantly
      with limitation of infarct size (r = 0.75, p = 0.002). Global preconditioning may
      account for the successful use of cross-clamp fibrillation during cardiac
      surgery.

PMID- 8298069
TI  - Pharmacokinetics of reversible metabolic systems.

PMID- 8298070
TI  - Comparative pharmacokinetics and pharmacodynamics of two marketed bid
      formulations of diltiazem in healthy volunteers.
AB  - Cardizem SR and Bi-Tildiem were both approved in their respective countries on
      the basis of clinical trials demonstrating efficacy and safety in the treatment
      of angina pectoris. In this cross-over randomized study, we assessed whether
      these two sustained-release formulations of diltiazem have equivalent
      pharmacokinetic and pharmacodynamic profiles. Twenty-four young healthy male
      volunteers were hooked to Holters and ambulatory blood pressure monitors for 24 h
      to establish baseline systolic blood pressure (SBP), diastolic blood pressure
      (DBP), sinus rate and PR intervals. They then received a single dose of 120 mg of
      diltiazem from one formulation. The pharmacodynamic measurements were recorded
      for a further 24 h and blood samples were collected over 36 h for evaluation of
      diltiazem in plasma by a high-performance liquid chromatogrpahic (HPLC) method.
      The procedures were repeated with the alternate formulation after a 7 d wash-out.
      Pharmacokinetics showed statistically significant (p < 0.01) differences in AUC0
      12 with means (+/- SD) of 519.2(+/- 172.8) and 429.6(+/- 147.2) ng h ml-1, AUC0
      36 of 835.6(+/- 281.6) and 730.9 (+/- 271.5) ng h ml-1 and Cmax of 89.1(+/- 30.3)
      and 61.1(+/- 21.2) ng ml-1 for Cardizem SR and Bi-Tildiem, respectively. The only
      pharmacodynamic parameter showing a statistically significant difference in
      change from baseline between the two formulations was DBP with mean (+/- SD)
      change in AUC0-12 of -13.6(+/- 20.8) and +8.4(+/- 31.7) mm Hg h (p = 0.0135) and
      in AUC0-24 of -33.0(+/- 43.7) and -0.3(+/- 59.2) mm Hg h (p = 0.0463) for
      Cardizem SR and Bi-Tildiem, respectively. These findings suggest that assessment
      of efficacy of sustained-release formulations of diltiazem by bioequivalence
      could be misleading. They also confirm that a single dose of diltiazem does not
      elicit a significant pharmacodynamic response in healthy volunteers. Equivalence
      for such formulations should therefore be demonstrated by pharmacodynamic
      evaluation or clinical studies in a patient population.

PMID- 8298071
TI  - The effect of food on the relative bioavailability of fadrozole hydrochloride.
AB  - The effect of food on the pharmacokinetic disposition of fadrozole hydrochloride
      was evaluated in nine healthy male and female volunteers. Single 12 mg doses of
      fadrozole were orally administered to subjects immediately following a
      standardized meal or after fasting for 12 h, in a randomized crossover design. No
      statistically significant treatment differences were detected for the
      pharmacokinetic parameters AUC and half-life. Cmax was significantly reduced by
      15% for the fed treatment relative to the fasted treatment, and tmax was delayed
      by 39%. These findings indicate that the concomitant ingestion of food with
      fadrozole delays the gastric emptying and/or absorption of fadrozole, but has no
      effect on the extent of absorption.

PMID- 8298072
TI  - Comparative bioavailability of propranolol following oral, intravenous and
      transdermal administration in rabbits.

PMID- 8298073
TI  - Differential OMP expression in opossum accessory olfactory bulb.
AB  - Using immunohistochemical techniques, olfactory marker protein (OMP) was
      localized to the main (MOB) and accessory (AOB) olfactory bulbs of 30- and 45-day
      old, and adult Brazilian opossums, Monodelphis domestica. Entire olfactory nerve
      and glomerular layers of the adult opossum MOB were darkly stained. In the adult
      AOB the rostral half of these two layers was stained more intensely than the
      caudal half, and both parts were less darkly stained than the MOB. This
      differential AOB staining was not present at 30 days of age, but was evident by
      postnatal day 45, although not as dramatic as in adults. This is the first report
      of differential OMP expression and may provide an approach to identifying the
      function of OMP.

PMID- 8298074
TI  - Effect of ketamine on stress protein immunoreactivities in rat olfactory mucosa.
AB  - Administration of 9 mg ketamine per 100 g b.wt. to rats leads to transient
      enhancement of immunoreactivity to monoclonal antibodies against two stress
      proteins, ubiquitin and human 70 kDa heat shock protein (HSP70), in the
      supranuclear region of supporting cells of the olfactory epithelium and in the
      Bowman's gland acinar cells in the subepithelial lamina propria. In the
      supporting cells the enhanced immunoreactivities are not caused by other drugs
      used in our surgical anesthetic/antibiotic regimen (xylazine, buprenorphine, and
      gentamicin), but in Bowman's glands they are. Results are discussed in terms of
      possible ketamine binding to phencyclidine receptors (either NMDA-associated or
      not) and possible direct stress-inducing interactions of ketamine or ketamine
      breakdown products with the inhalant detoxification or secretory systems in the
      reactive cells.

PMID- 8298075
TI  - Twitch/tetanus ratio and its relation to other properties of motor units.
AB  - The ratio of single twitch tension to maximal tetanic tension (Tw/Tet ratio)
      represents one of the physiological properties of single motor units. In our
      study, in agreement with the results of other studies, the mean Tw/Tet ratio of
      slow motor units was lower than that of fast motor units. But we found that the
      Tw/Tet ratios of the slow motor units with twitch tension between 0.75 and 1.5 g
      were higher than those of fast motor units with twitch tension in the same range.
      A significant linear relation between Tw/Tet ratio and twitch tension was
      obtained for the three types of motor units. This relationship could be due to
      the increasing number of muscle fibres within a motor unit with the twitch
      tension.

PMID- 8298076
TI  - Photoresponsive pacemaker neurons from the dissociated retina of Aplysia.
AB  - Isolated retinal pacemaker neurons of Aplysia devoid of any morphologically
      specialized photoreceptive processes responded to illumination. Neurons were
      dissociated from other retinal cells and maintained in primary culture for whole
      cell recording. The membrane potential was depolarized and action potentials were
      evoked by illumination. Light adaptation diminished the response and prolonged
      the latency. Under voltage clamp neurons responded with increased inward current.
      Responses were slower and smaller than specialized photoreceptor responses. Pairs
      and small clusters of monopolar neurons also responded to light. These
      photoresponsive monopolar neurons are likely to be the output neurons of the
      ocular circadian clock. Although photoresponsive central neurons have been
      described in Aplysia, this is the first report of photoresponses from isolated
      retinal neurons.

PMID- 8298077
TI  - Extracellular pH and buffering power determine intracellular pH in cortical brain
      slices during and following hypoxia.
AB  - 1H and 31P nuclear magnetic resonance (NMR) spectroscopy were used to study the
      role of external pH (pHo) in regulation of intracellular pH (pHi) in the cerebral
      cortex in vitro. Lowering the pH of the oxygenated superfusion medium (pHb) from
      7.5 to 7.0-6.8 decreased pHi from 7.33 +/- 0.08 to approximately 7.00
      independently of the presence of HCO3- and medium buffering power. Reduction of
      medium (pHb 6.8) buffering power during hypoxia severely acidified pHi
      independently of the presence of HCO3-. Following hypoxia, recovery of pHi was
      not sensitive to pHb provided that medium buffering was maintained. Lactate
      removal proceeded independently of pHb, HCO3- and external buffering power. These
      results indicate that decrease in extracellular buffering capacity has a feed
      back effect on pHi in the cerebral cortex.

PMID- 8298078
TI  - Direct evidence for the synaptic resonance phenomenon.
AB  - Via the parameter optimization method, well documented in the literature, data on
      the facilitated release of acetylcholine from the preganglionic nerve terminals
      during short trains of impulses have been quantitatively generalized within the
      framework of the previously developed theory of the double barrier synapse. This
      allowed unique transformation of the set of discrete measurements of facilitated
      transmitter release into continuous dependencies of facilitation on time and
      frequency and, subsequently, into the resonant curves having very readily
      interpreted computational meaning. Thus direct evidence is produced that an
      overall effect of facilitory action of presynaptic stimulation does indeed
      reflect resonant properties of the terminal in a form of the previously predicted
      synaptic resonance phenomenon.

PMID- 8298079
TI  - Ionic basis for intrinsic 40 Hz neuronal oscillations.
AB  - We present a biophysical model of a slowly inactivating potassium ion current
      IKS, based on recent voltage-clamp data from layer V pyramidal neurons in the cat
      sensorimotor cortex and show that the interplay between a persistent sodium
      current INaP and IKS is able to produce intrinsic membrane potential oscillations
      in the 10- to 50-frequency range. A most notable characteristic of such
      rhythmicity is what may be termed mixed-mode bursting, where clusters of action
      potentials alternate in time with epochs of small subthreshold oscillations.

PMID- 8298080
TI  - HU-211, a non-psychotropic cannabinoid, rescues cortical neurones from excitatory
      amino acid toxicity in culture.
AB  - The present study examined potential neuroprotective effects of HU-211, a
      synthetic non-psychotropic cannabinoid with non-competitive NMDA antagonist
      properties on neurones exposed to various excitotoxins in culture. HU-211 was
      found to protect neurones from NMDA and quisqualate-induced toxicity but not that
      produced by AMPA or kainate. NMDA-mediated neurotoxicity was blocked by HU-211 in
      a dose dependent manner with an EC50 = 3.8 +/- 0.9 microM. Radioligand binding
      studies have shown that HU-211 inhibits the binding of [3H]MK-801 to rat
      forebrain membranes (KI = 11.0 microM +/- 1.323) in a competitive manner, but was
      unable to displace [3H]kainate and [3H]AMPA binding. These data suggest that the
      neuroprotective activity of HU-211 is directly associated with the NMDA receptor
      channel and possibly with the quisqualate receptor of the metabotropic class.
      Thus, HU-211 appears to act as an NMDA open channel blocker and shows promise as
      a novel neuroprotectant for clinical use.

PMID- 8298081
TI  - Lithium enhances 5-HT2A receptor-mediated c-fos expression in rat cerebral
      cortex.
AB  - The role of lithium in treating bipolar affective disorder is poorly understood;
      however, it may involve effects on brain 5-HT function. We have shown that the 5
      HT2A/2C receptor agonist DOI (2,5-dimethoxy-4-iodophenylisopropylamine) induces
      the expression of c-fos in rat brain which correlates with the distribution of 5
      HT2A receptors. We now report on the effect of lithium on 5-HT receptor
      activation. Rats were treated chronically with dietary lithium before being given
      either DOI or the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n
      propylamino) tetralin), and their brains were processed for c-fos
      immunohistochemistry. Lithium treatment greatly enhanced levels of Fos seen after
      DOI, but not after 8-OH-DPAT; layer II of caudal piriform cortex, previously
      devoid of staining, exhibited the most marked labelling. This suggests that
      chronic lithium selectively alters immediate-early gene expression in brain. Such
      alteration may underlie the action of lithium in treating bipolar affective
      disorder.

PMID- 8298082
TI  - Neuroprotection against nitric oxide injury with inhibitors of ADP-ribosylation.
AB  - We investigated the effect of nitric oxide (NO) upon CA1 neurons of the
      hippocampal slice. NO was given via perfusate without oxygen and with glucose
      concentration increased to 10 mM to prevent hypoxic injury. Exposure to NO for 10
      min produced severe neuronal injury, with CA1 orthodromic and antidromic
      population spike regaining only 3 +/- 3% and 9 +/- 3% of initial amplitude after
      1 h recovery. Hypoxic controls in contrast, showed orthodromic and antidromic
      recovery of 98 +/- 5% and 93 +/- 7%. Good protection from NO-induced injury was
      seen with 10 mM nicotinamide, an inhibitor of poly-ADP-ribosylation, with CA1 PS
      recovering to 116 +/- 10% orthodromically, and 96 +/- 4% antidromically.
      Protection was also seen with 3'-aminobenzamide, another poly-ADP-ribosylation
      inhibitor, suggesting that poly-ADP-ribosylation may play an important role in NO
      mediated neuronal injury.

PMID- 8298083
TI  - Diazoxide suppresses slowly-inactivating outward and inward currents in CA1
      hippocampal neurones.
AB  - Diazoxide (DZX) opens ATP-sensitive K (KATP) channels in muscle and other cells.
      In whole-cell voltage-clamp recordings in slices, in the presence of kynurenate
      and bicuculline to minimize indirect effects, DZX (0.65 mM) did not increase
      input conductance; but it sharply reduced persistent inward and outward currents.
      An inward current (peak near -20 mV) was especially clear in the presence of K
      channel blockers; was fully evident in Ca-channel blocking medium; but was
      abolished by tetrodotoxin. The main direct effects of DZX on these neurones are
      thus mediated not by activation of KATP channels, but rather by modulation of
      voltage-dependent channels, including a TTX-sensitive persistent NA current and
      possibly a Ca current.

PMID- 8298084
TI  - Suppressive effect of simultaneous injection of ACTH1-10 and beta-endorphin on
      brain [3H]flunitrazepam binding.
AB  - Seven-day hypophysectomized rats were intracerebroventricularly (i.c.v.) injected
      with beta-endorphin, ACTH1-10 or beta-endorphin+ACTH1-10 (10-20 ng of each
      compound) and the [3H]flunitrazepam ([3H])FNZ) binding to the rat cerebral cortex
      of hypophysectomized rats was assayed one hour later. The i.c.v. injection of
      ACTH1-10 (10-20 ng) or beta-endorphin (10-20 ng) significantly increased [3H]FNZ
      binding to a similar extent. The effect of i.c.v. injection of ACTH1-10 on brain
      binding was blunted by simultaneous beta-endorphin administration at the same
      doses. The i.c.v. naloxone injection (10-20 ng) did not modify the effect of
      ACTH1-10 (10 ng) on [3H]FNZ binding, but counteracted, in a dose-related manner,
      the blocking effect of beta-endorphin on ACTH1-10-dependent brain [3H]FNZ
      binding. The results suggest the existence of an opioid-melanopeptide integration
      to control brain benzodiazepine receptors.

PMID- 8298085
TI  - Hypothalamic norepinephrine depletion inhibits CRF-41 release following neural
      stimuli.
AB  - The effects of depletion of hypothalamic norepinephrine (NE) on median eminence
      (ME)-corticotropin-releasing factor (CRF-41) content, serum ACTH and
      corticosterone (CS) levels, following photic and acoustic stimulation, were
      investigated. While in intact rats these stimuli caused depletion in CRF-41 and a
      rise in ACTH and CS level, in rats pretreated with 6-hydroxydopamine (6-OHDA),
      these effects were prevented. This would suggest that the blockage in the release
      of ME CRF-41 into the portal plasma following neural stimuli in rats with
      hypothalamic NE depletion, is responsible for the inhibition of the pituitary
      adrenocortical response.

PMID- 8298086
TI  - Isolation of a glycosyl-phosphatidylinositol (GPI) from rat brain.
AB  - Brain lipids were labelled with [1-14C]-isethionyl acetimidate and purified by
      sequential thin layer chromatography. Four labelled peaks were obtained, the
      first ones migrating with the same Rf as glycosyl-phosphatidylinositol (GPI).
      Further proof of the isolation of GPI was obtained by the observations that 44.8%
      of the radioactivity associated with the lipid in peak I was converted to the
      water phase by the effect of a PI-specific phospholipase C, and that the soluble
      material so obtained produced a dose-dependent inhibition of cAMP-dependent
      protein kinase activity. These findings indicate a biological equivalence between
      GPI and its polar head group from rat brain and those described in other cell
      types, and are consistent with the proposed role of these molecules in cellular
      signalling.

PMID- 8298087
TI  - Intraventricular beta-endorphin accumulates in DARPP-32 immunoreactive tanycytes.
AB  - Intraventricularly administered beta-endorphin (beta-end) (50-500 pmol) is found
      to be taken up and accumulated in dopamine and adenosine 3',5'-monophosphate
      regulated phosphoprotein (DARPP-32) positive tanycytes of the median eminence 15
      min after injection as revealed by double immunolabelling procedures in
      combination with confocal laser microscopy. Exogenous beta-end in the
      cerebrospinal fluid (CSF) may in this way regulate the hypothalamic hormone
      release at the nerve terminal level by being released from tanycytes in the
      external layer or by affecting tanycyte function. The findings open up the
      possibility that neuronal beta-end via volume transmission in the CSF and
      internalization into tanycytes may exert in part its actions on hypothalamic
      hormone secretion by actions in the median eminence.

PMID- 8298088
TI  - Co-expression of HSP72 and c-fos in rat brain following kainic acid treatment.
AB  - The relationship between heat shock protein 72 (HSP72) and c-fos gene expression
      following systemic administration of kainic acid was investigated by combining
      immunocytochemistry for HSP72 with in situ hybridization for c-fos. Increased
      HSP72 expression was detected in adult rat hippocampus 4 h after seizure-onset.
      Transient co-expression of c-fos and HSP72 occurred in neurons that are resistant
      to kainic acid, whereas prolonged co-expression was observed in vulnerable
      neurons. The spatial distribution and developmental time course of kainic acid
      induced HSP72 expression were similar to those of kainic acid-induced
      neurodegeneration. The results demonstrate a relationship between c-fos and HSP72
      gene expression and suggest that prolonged co-expression of these genes plays a
      role in kainic acid-induced neuronal death.

PMID- 8298089
TI  - Nerve growth factor mRNA is expressed by GABAergic neurons in rat hippocampus.
AB  - Isotopic and colorimetric in situ hybridization techniques were combined to
      determine if nerve growth factor (NGF) mRNA is colocalized with mRNA for the GABA
      biosynthetic enzyme glutamic acid decarboxylase (GAD) in adult rat hippocampus.
      Quantification of neurons labeled with both 35S-labeled GAD67 mRNA and
      digoxigenin-labeled NGF cRNA determined that of the NGF cRNA-labeled neurons, 97%
      within regions CA3-CA1, and 88% within the hilus, were also labeled with GAD67
      cRNA. Overall, 47% of the total population of GAD67 cRNA labeled cells were NGF
      cRNA positive. The greater portion of stratum granulosum was lightly labeled by
      the NGF cRNA alone. The results indicate that, excepting stratum granulosum, NGF
      is predominantly synthesized by GABAergic neurons in rat hippocampus.

PMID- 8298090
TI  - Antisense oligonucleotide to c-fos induces ipsilateral rotational behaviour to d
      amphetamine.
AB  - The immediate-early genes, especially c-fos, have been suggested to have an
      important role in neuronal plasticity and memory. However, it has been difficult
      to determine if in fact c-fos can participate in control of behaviour. Here we
      can report that direct unilateral infusion into the rat neostriatum of an
      antisense phosphothioate oligodeoxynucleotide to c-fos mRNA leads to the rapid
      induction of ipsilateral rotational behaviour after d-amphetamine administration.
      This is associated with an elimination of the in vivo expression of Fos-like
      immunoreactivity within the infused region of neostriatum. Following infusion of
      these oligodeoxynucleotides labelled with fluorescein isothiocyanate they appear
      with a nuclear and cytoplasmic location in a large number of nerve cells, many of
      which are immunoreactive for dopamine and cyclic AMP regulated phosphoprotein.
      The present findings suggest that the immediate-early gene c-fos has a role also
      in control of behavioural activity, as illustrated in D1 receptor containing
      striatal neurones.

PMID- 8298091
TI  - Brain infarction is not reduced in SOD-1 transgenic mice after a permanent focal
      cerebral ischemia.
AB  - Using a mouse model with intraluminal blockade of the middle cerebral artery
      (MCA) which produced both cortical and striatal infarction, the effect that
      superoxide radicals have on cerebral infarction, local cerebral blood flow, and
      neurological deficits after 24 h of permanent focal cerebral ischemia in
      transgenic mice (Tg) overexpressing human CuZn-superoxide dismutase (SOD-1) was
      examined. There were no difference between SOD-1 Tg mice and non-Tg littermates
      observed in the infarct areas of brain slices, the infarct volume, the local
      cerebral blood flow, or the neurological deficits. These data suggest that pre
      existing high levels of antioxidant enzyme failed to provide neuronal protection
      against permanent focal cerebral ischemia.

PMID- 8298092
TI  - Localization of neurotrophin receptors in olfactory epithelium and bulb.
AB  - We used in situ hybridization to localize trk, trkB and trkC mRNA, in rat and cat
      olfactory bulb. Expression of mRNA encoding truncated trkB receptors was seen in
      all layers, while only very modest full-length trkB expression could be detected.
      trkC hybridization was seen in all layers, most dense in the mitral cell layer.
      The localization of full-length tyrosine kinase trkB receptor in olfactory bulb
      and epithelium was examined with immunohistochemistry. trkB-like immunoreactivity
      was seen in the fila olfactoria, epithelium and in vitro, in olfactory sensory
      neurones. Since BDNF is expressed by olfactory sensory neurone target cells in
      the olfactory bulb, these data suggest that BDNF may act as a target derived
      neurotrophic factor in the primary olfactory system.

PMID- 8298093
TI  - c-fos antisense generates apomorphine and amphetamine-induced rotation.
AB  - Sodium pentobarbital anaesthetized rats were injected ipsilaterally with an
      antisense oligonucleotide to c-fos and contralaterally with a sense of
      oligonucleotide to c-fos in the striatum. Ten hours later they were injected with
      amphetamine or apomorphine and their behaviour was observed for a further 2 h at
      which time they were overdosed with anaesthetic and their brains were removed,
      frozen and processed for Fos and Jun B immunohistochemistry. Rats showed
      amphetamine- and apomorphine-induced rotation towards the antisense injected
      striatum. The antisense oligonucleotide also strongly inhibited the amphetamine
      induced expression of c-Fos and Jun B in striatal neurones. These results suggest
      that antisense to c-fos produces a biochemical change in the injected striatum
      that then, 10 h later, blocks amphetamine- and apomorphine-induced behavioural
      and biochemical effects.

PMID- 8298094
TI  - Selection of speech messages in free-field listening.
AB  - Event-related brain potentials (ERPs) elicited by initial consonants of words in
      a spoken message were recorded from 10 human subjects. In an ecologically valid
      free-field situation, brain responses to speech were recorded for the first time
      without using artificial probe stimuli as ERP trigger signals. In an analogy to a
      'Cocktail-Party' situation in its most elementary form, two concurrent stories
      were delivered via separate left and right loudspeakers. The subject's task was
      to selectively attend to a designated message while ignoring the other. Results
      show a very early attention effect for a speech message commencing at about 40 ms
      from stimulus onset. This early effect appears to be based on tonic facilitation
      of the attended message and contextual cues.

PMID- 8298095
TI  - Event-related potentials reveal a memory trace for temporal features.
AB  - Auditory event-related potentials (ERPs) were recorded from reading subjects
      while they were presented with 50 ms tone pips intervened by regular silent
      intervals of 550 ms. This interval was occasionally shortened either to 250, 100,
      25, 10, or 2 ms, which resulted in the elicitation of the mismatch-negativity
      (MMN), a change-specific ERP component not elicited by tones appearing after the
      regular, longer intervals. This indicates that the MMN is not just due to new
      afferent elements activated by deviant but not standard stimuli. In addition, the
      present results suggest that the temporal parameters of acoustic stimulation are
      also encoded in memory traces which therefore are representations of auditory
      events rather than only of static stimulus aspects.

PMID- 8298096
TI  - NMDA-receptors and potentiation in an area of avian brain essential for learning.
AB  - The intermediate medial part of the hyperstriatum ventrale (IMHV), part of the
      avian forebrain, is essential for early learning in the domestic chick.
      Persistent potentiation (PP) can sometimes be induced in the IMHV in vitro. One
      can predict success from events which occur during the stimulation (1 min at 5
      Hz) which is used for induction: the original response must be transiently
      replaced by a later, slower response (the LPSR). The LPSR has a comparatively
      high threshold of activation, its rate of development is inversely related to
      magnesium concentration and it can be eliminated by NMDA antagonists, as can the
      induction of PP. PP in the IMHV is therefore dependent upon NMDA receptors and
      the LPSR represents the activation of these receptors.

PMID- 8298097
TI  - Synaptic potentiation in the rat dentate gyrus during exploratory learning.
AB  - To investigate whether hippocampal synaptic transmission is enhanced during
      learning, we recorded synaptic field potentials in the dentate gyrus in response
      to stimulation of the perforant path in rats exploring a novel environment.
      Because these signals rapidly grow during brain temperature elevation, caused by
      any motor activity, the potentials were compared with signals sampled at similar
      brain temperatures after passive warming. Both the field excitatory postsynaptic
      potential (f-EPSP) and the population spike increased significantly early in the
      exploration, relative to temperature-matched control potentials. The effect
      decayed within 15-30 minutes. This is the first demonstration of a temperature
      independent synaptic potentiation in the hippocampus during learning about the
      environment. The time course is similar to that of short-term potentiation.

PMID- 8298098
TI  - NADPH-diaphorase (NOS) is induced in pyramidal neurones of hippocampal slices.
AB  - We found NADPH-diaphorase (presumably identical with nitric oxide synthase) in
      pyramidal neurones of the hippocampus in slices that stayed in a chamber for 30
      min or longer. In some instances parallel slices showed normal membrane
      properties when studied electrophysiologically. In freshly made slices the
      pyramidal neurones were not stained. Thus, after induction of the enzyme, the
      hippocampal pyramidal neurones can synthesize nitric oxide which may serve as a
      retrograde messenger in long-term potentiation. The enzyme may also play a role
      in cell loss seen in slices which stayed in a chamber for 9-22 h before fixation.

PMID- 8298099
TI  - Spatial discrimination learning induces LTP-like changes in the lateral septum of
      mice.
AB  - The efficacy of synaptic transmission from the fimbria to the lateral septum (LS)
      of freely moving mice was monitored electrophysiologically over 9 days of
      training in a spatial discrimination task (radial maze). Electrical stimulation
      of the fimbria evoked two negative waves (N2 and N3) in the ipsilateral LS.
      Compared to a control group exposed to muscular effort (treadmill), trained
      animals displayed a significant and progressive increase in the amplitude of N3
      with no changes in N2. Moreover, this increase was of greater magnitude in fast
      learners than in slow learners and persisted for at least 24 h following the last
      (9th) training session. These changes might play a role in spatial learning
      through the regulation of septohippocampal cholinergic activity.

PMID- 8298100
TI  - Immunofluorescent identification of a delta (delta)-opioid receptor on primary
      afferent nerve terminals.
AB  - Antisera were produced against synthetic peptides predicted from the recent
      cloning of a delta opioid receptor, DOR-1. Confocal microscopic examination of
      immunostained spinal cord sections revealed that DOR-1 immunoreactive (-ir) nerve
      fibers and terminals form a moderately dense plexus within the superficial dorsal
      horn of rats and mice. These fibers decreased dramatically following dorsal
      rhizotomy and consistent with these observations a population of small diameter
      neurons in ganglia exhibited DOR-1-ir. DOR-1-ir ganglion neurons were also
      immunoreactive for calcitonin gene-related peptide (CGRP), and their terminals in
      the spinal cord contained both CGRP- and DOR-1-ir, the latter presumably located
      as a 'presynaptic' receptor. Interestingly, terminals containing DOR-1-ir
      appeared to be closely apposed by fibers and terminals containing enkephalin
      (ENK)-ir, which suggests that ENK may be a physiologically relevant ligand for
      the receptor encoded by DOR-1, and that DOR-1 may act to regulate the release of
      transmitters from small diameter primary afferent neurons.

PMID- 8298101
TI  - Neurite outgrowth inhibitors associated with glial cells and glial cell lines.
AB  - 'Reactive' astrocytes and 'activated' microglial cells are the major cellular
      components of gliotic tissue, one of the most serious obstacles to axonal
      regeneration in mammalian central nervous system grey and white matter. The
      appearance of reactive glial cells after a lesion in the CNS correlates with the
      expression of molecules, like proteoglycans, capable of preventing neurite
      outgrowth. Co-cultures of embryonic neurones with glial cells and glial cell
      lines, that might share characteristics with reactive astrocytes and microglial
      cells, show that while cultured astrocytes promote neurite outgrowth, plasma
      membranes of C6 glioma and microglial cells express neurite inhibitory activities
      with proteoglycan-like characteristics, similar to those expressed by the gliotic
      tissue associated inhibitors. These results suggest that in vivo microglial cells
      might be at least one of the sources of proteoglycans with neurite outgrowth
      inhibitory properties.

PMID- 8298102
TI  - trkC expression in the injured rat spinal cord.
AB  - Reactive non-neuronal cells express high levels of low-affinity neurotrophin
      receptor and truncated trkB receptors after spinal cord injury. Here we report
      that descending nerve fibres in the rat lateral spinal cord column show strong
      trkC-like immunoreactivity after traumatic spinal cord lesions in the adult rat.
      No change in trkC expression by glial cells could be detected by
      immunohistochemistry or in situ hybridization at the lesion site. The data
      suggest that regeneration of descending spinal cord axons could be encouraged by
      the trkC ligand, neurotrophin 3.

PMID- 8298103
TI  - Decelerated migration of neocortical neurones in explant culture after exposure
      to radiation.
AB  - We describe a newly devised explant culture system employing rat neocortex in
      which neurones migrate in a fashion similar to that seen in vivo. Using
      neocortical explant culture we have demonstrated an effect of ionizing radiation
      on neuronal migration at doses as low as 10 cGy together with a changing pattern
      of expression of the neural cell adhesion molecule N-CAM. After a dose of more
      than 10 cGy there was a significant reduction in N-CAM immunoreactivity in the
      matrix cell zone. We do not know the reason why the reduction in N-CAM
      immunoreactivity is so localized, although it is not unlikely that the most
      active site in terms of N-CAM synthesis is significantly affected by radiation.

PMID- 8298104
TI  - GPA and CNTF produce similar effects in sympathetic neurones but differ in
      receptor binding.
AB  - The effects of growth promoting activity (GPA) on sympathetic neurone development
      were investigated in vitro and compared with the effects of ciliary neurotrophic
      factor (CNTF). GPA interfered with sympathetic neurone proliferation and induced
      the expression of vasoactive intestinal peptide (VIP) in neurones from 7-day-old
      (E7) chick embryos. The biological effects observed with saturating levels of GPA
      are indistinguishable from the effects of CNTF. The effects on VIP expression
      suggest that GPA may be involved in the specification of sympathetic neurone
      phenotypes. Whereas half maximal effects are achieved at lower concentrations of
      GPA than CNTF, GPA competes less efficiently than CNTF for the binding of 125I
      labelled CNTF. This suggests similar, but not identical interactions of CNTF and
      GPA with receptors on chick sympathetic neurones.

PMID- 8298105
TI  - Axotomy induces NADPH diaphorase activity in neonatal but not adult motoneurones.
AB  - Rat sciatic motoneurones do not normally express NADPH diaphorase activity.
      However, after cutting the sciatic nerve in the mid-thigh of neonates and
      applying the retrograde tracer fast blue, such reactivity was found colocalized
      with fast blue in about one-fifth of sciatic motoneurones 4 days following the
      lesion. This proportion of sciatic motoneurones expressing NADPH diaphorase
      activity remained approximately constant for 14 days after axotomy during which
      time extensive motoneurone death occurred. Many NADPH diaphorase-positive
      motoneurones appeared shrunken with degenerative changes to the nucleus. In
      contrast, the same lesion in adult animals failed to induce any reactivity or
      cause motoneurone death 4-28 days after axotomy. Induction of nitric oxide
      synthesising capability may play a role in the death of target-deprived immature
      motoneurones.

PMID- 8298106
TI  - Visual experience during postnatal development determines the size of optic nerve
      axons.
AB  - The size of any axon is generally related to an internal programme (probably
      common for all neurones) that determines the number and organization of its
      cytoskeletal components. Here we show that axons from visually deprived rats are
      smaller than controls, although the number of microtubules and neurofilaments
      remains unchanged. Moreover the distance between both microtubules and
      neurofilaments and the amounts of 200 kDa, 160 kDa and 68 kDa neurofilament
      proteins are also diminished in the deprived axons. We suggest that cytoskeletal
      organization and axonal calibre are not only determined by intrinsic (genomic)
      factors, but that environmental stimulation is important for normal growth of
      nerve cells.

PMID- 8298107
TI  - [The hemodynamics and anatomy of the circle of Willis. The technic and clinical
      value of selective MR angiography].
AB  - This study evaluates the usefulness of MR angiography in analysing the individual
      collateral flow dynamics and anatomy of the circle of Willis in 56 patients with
      high-grade extracranial carotid stenosis or occlusion. Selective MRA of the
      carotid or vertebrobasilar area was performed by means of presaturation up to the
      brain-supplying arteries at the level of the middle neck (angled presaturation
      slabs). Results obtained with selective and non-selective MRA in 56 consecutive
      patients were compared with the findings at transcranial Doppler ultrasonography
      and arterial angiography. Ischaemic cerebral infarctions were classified by
      computerized tomography and correlated with the results of collateral flow
      analysis: Sensitivity of selective MRA in detecting intracranial collateral flow
      via anterior or posterior communicating artery was 96 and 97%, respectively;
      sensitivity in depicting extracranial transorbital flow was lower (71%). Non
      selective MRA was 100% sensitive in detecting a non-filling of the horizontal
      (A1) segment of the anterior cerebral artery and in identifying an origin of the
      posterior cerebral artery from the intracranial carotid artery. Slow flow
      infarctions occurred more frequently in patients with transorbital and posterior
      to-anterior collateral flow than in patients with collateral flow via anterior
      communicating artery.

PMID- 8298108
TI  - [Osseous variations in the coronary CT of the paranasal sinuses].
AB  - Bony variations in the anterior ethmoids may, if severe, play an important role
      in the development of chronic sinusitis and present the surgeon with added risks
      during operation. We have, therefore, analysed 390 preoperative CT examinations
      of the sinuses performed in the coronary plane with respect to the frequency of
      bone variations. Concha bullosa, increased pneumatisation of the agger nasi,
      large ethmoidal bullae, Haller's cells and increased pneumatization of the
      sphenoid were found with equal frequency in about 20%. The most common variants
      occurred in the uncinate process (31.5%), less common were paradoxical curve of
      the middle turbinates (13.3%) and very rare were Onodi cells (1.3%).

PMID- 8298109
TI  - [Motility disorders of the esophagus--their diagnosis with a rice-barium meal].
AB  - The purpose of this study was to evaluate the role of a "barium-rice" study for
      diagnosis of dysphagia and oesophageal motility disorders. MATERIAL AND METHODS:
      203 patients with oesophageal motility disorders of various aetiologies were
      examined by both conventional barium study and a "barium-rice" study. During the
      latter, oesophageal clearance of a defined mixture of barium sulfate and boiled
      rice was measured. RESULTS: The conventional barium study revealed prolonged
      transit time in only 15.8% (32 of 203 cases), whereas barium-rice study was
      pathological in 50.8% (103 to 203 cases). In 71 of 171 patients (41.5%) with a
      normal barium study, barium-rice passage was prolonged. In 23 patients,
      radiological results were confirmed by manometric measurements. CONCLUSION:
      Oesophageal motility disorders are detected by a barium-rice study with high
      sensitivity independent of the underlying disease. The barium-rice study offers a
      simple diagnostic tool revealing quantitative and reliable results. The barium
      rice study is a suitable method for screening and follow-up of patients with
      dysphagia and oesophageal motility disorders.

PMID- 8298110
TI  - [The results of a long-term follow-up of patients with a percutaneous
      cholecystostomy].
AB  - 19 out of 37 patients with percutaneous cholecystostomy were followed up for
      assessment of gallbladder function after percutaneous drainage. 17 out of 19 of
      the patients remained free from symptoms of gallbladder disease during a mean
      follow-up period of 25.8 months. Contractility of the gallbladder calculated by
      measurement of the sonographic diameter of the gallbladder with provocation tests
      was 62%. One patient was operated upon for choledocholithiasis three years after
      percutaneous cholecystostomy. Histology showed signs of chronic cholecystitis. It
      can be concluded that cholecystectomy is not routinely necessary after
      percutaneous cholecystostomy provided biliary excretion is normal.

PMID- 8298111
TI  - [Atypically located pancreatic pseudocysts in the liver, spleen, stomach wall and
      mediastinum: their CT diagnosis].
AB  - It was the aim of this computed tomography study to analyse the frequency,
      morphology, and cause of atypically located pancreatic pseudocysts. Of 236
      patients with acute (n = 87) or chronic (n = 149) pancreatitis, 85 (36%) had
      pancreatic pseudocysts. Pancreatic pseudocysts atypically located in the liver,
      spleen, stomach wall or mediastinum were diagnosed in 19 (22.4%) of the 85
      patients. The mean size of intrapancreatic, parapancreatic, and atypically
      located pseudocysts was 2.7, 4.4, and 7.5 cm, respectively. The density values of
      atypically located pseudocysts did not differ significantly from those of
      intra/parapancreatic pseudocysts. The natural pathways along which atypically
      located pseudocysts develop primarily are the hepatoduodenal, gastrohepatic, and
      gastrosplenic ligaments.

PMID- 8298112
TI  - [MRT for surgical planning in anal atresia].
AB  - We evaluated in this study the value of preoperative examinations of anal atresia
      with an optimised MRI strategy. 13 patients with anorectal anomalies, most of
      them younger than one year, underwent an MRI examination of the pelvis. 10 of
      these patients were operated afterwards. Compared with the situs shown by the
      operation the results of the MRI examination were very exact in all cases in
      respect of the level of atresia and the development of the striated muscle
      complex. Fistulas could be completely described in most cases. MRI demonstrated
      additional lesions in some patients which were of great importance for planning
      the further treatment of the patients. As a consequence MRI can give valid
      information on anal atresia for planning the operative treatment.

PMID- 8298113
TI  - [Tumorous space-occupying lesions of the tibia. A radiological analysis of 459
      cases].
AB  - The patients' age, location and radiography of 459 bone tumours and tumour-like
      lesions of the tibia were analysed retrospectively. 79.2% of all lesions were
      benign, and the portion of malignant tumours increased with increasing age.
      Predominantly malignant tumours were found in a distal central metadiaphyseal
      (100%), in proximal central epimetadiaphyseal (90%) and in a proximal central
      metadiaphyseal (63%) location. Lesions showing a growth rate according to Lodwick
      IA and those to IB were benign in 99.5% and in 95.4%, respectively. In contrast,
      tumours showing a grade II or III were malignant in 85.2% and 100% of cases,
      respectively. Through the construction of subgroups by combination of patients'
      age, location and growth rate special tumours were selected in that way, that
      they were predominantly found in that subgroups.

PMID- 8298114
TI  - [MRT-specific staging of chondromalacia patellae with the aid of a special knee
      compressor: a comparison with the arthroscopic findings].
AB  - The present study proposes a new MRI-specific staging of chondromalacia patellae
      (CMP) which is based on cartilage thickness decrease and signal intensity
      behaviour under compression as well as cartilage morphology in the plain image.
      The investigation was performed in 30 patients with varying knee complaints who
      underwent arthroscopy after MR imaging. It was demonstrated that three CMP stages
      can already be differentiated by MRI under compression in arthroscopically
      healthy cartilage. This proves a marked improvement in the early diagnosis of
      CMP.

PMID- 8298115
TI  - [The CT classification of intra-articular calcaneus fractures].
AB  - 93 patients with 102 intraarticular calcaneus fractures (ICF) were examined by CT
      from 1986 to 1992. The images were evaluated with the use of a modified
      classification based on the number of fractured heel bone facets (2 facets in
      4.8%, 3 facets in 53.9%, 4 facets in 32.3%, comminution in 8.8% of the
      fractures), the involvement of the calcaneus-cuboid joint (60.8%) and the
      fracture mechanism (tongue-type in 28.4%, joint depression in 62.7%) with the
      weight-bearing calcaneal compartments taken into special consideration. In that
      way, each intraarticular calcaneus fracture could be scored, enabling a fast
      diagnosis comprising factors relevant for the therapy and prognosis.

PMID- 8298116
TI  - [Bone marrow involvement in Hodgkin's disease: MR tomography and chemical-shift
      imaging].
AB  - The ranking of magnetic resonance imaging (MRI) and chemical shift imaging (CSI)
      of the bone marrow was assessed in 30 patients in the initial staging of
      Hodgkin's disease or in the restaging after relapse. The results were compared
      with other staging procedures, especially trephine biopsies. Pathologic findings
      were divided into diffuse and focal lesions resulting in a better differentiation
      between malignant infiltrations and unspecific marrow reactions that are common
      in Hodgkin's disease. Diffuse changes were unspecific, a diffuse marrow
      infiltration could not be established in 7 patients. Focal lesions proved to be
      infiltrations in 6 of 7 patients; only in one case an unspecific marrow reaction
      was found on histology. CSI showed a pathological increase of the relative water
      signal in focal and diffuse marrow changes, and made no individual diagnostic
      contribution.

PMID- 8298117
TI  - [Pneumothorax prevention with coagulated blood after percutaneous lung biopsy].

PMID- 8298118
TI  - [The "turning maneuver"--an intubation aid in enteroclysis].

PMID- 8298119
TI  - [Isolated horizontal fracture of the anterior arch of the atlas].

PMID- 8298120
TI  - [Radioulnar synostoses].

PMID- 8298121
TI  - [Tuberculous granuloma of the tibia in an HIV patient].

PMID- 8298122
TI  - [The contributions of magnetic resonance tomography to current problems of
      expertise. Muscle substance loss after trauma].

PMID- 8298123
TI  - [Direct echinococcal cyst rupture as a sequela to trauma].

PMID- 8298124
TI  - Severe combined immunodeficiency, interleukin-2 (IL-2), and the IL-2 receptor:
      experiments of nature continue to point the way.
AB  - The recent discovery of molecular defects in three forms of X-linked
      immunodeficiency has quickly transformed the study of immunodeficiency into one
      of the most exciting in basic and clinical immunology. The identification of
      defects in the IL-2R gamma chain in the etiology of X-linked SCID has suggested a
      heretofore unanticipated functional role of the gamma chain in immunologic
      development. While new and novel cytokines and cytokine receptors continue to be
      identified, it has become clear that our knowledge of IL-2, one of the best
      understood cytokine/receptor systems, is far from complete. Clarifying the
      molecular interactions between IL-2 and its receptor complex will improve the
      sophistication with which these interactions are manipulated in the clinic for
      the treatment of autoimmune disorders and allograft rejection, treatment of
      lymphoid malignancies, and cytokine-based therapies for immunotherapeutic
      treatment of nonlymphoid cancers. Recent gene therapy approaches to the treatment
      of children with the ADA-deficient form of SCID offers yet another exciting path
      for investigation. The use of retrovirally infected cord blood hematopoietic
      progenitor cells in attempts to reconstitute the immune system of ADA-deficient
      SCID children with ADA-producing cells raises the possibility of similarly
      "correcting" the defect in X-linked SCID. Such approaches almost certainly loom
      on the near horizon for other diseases. However, in view of the complexity and
      potentially pleiomorphic nature of defects in the IL-2R gamma chain, both in
      terms of their identification and correction, gene therapy for treatment of X
      linked SCID will require a thorough understanding of the molecular nature of the
      respective defects. Effective therapy will require precise knowledge of the
      defects, in terms of their influence on the ligand, receptor, and signaling
      apparatus, as well as their potential effects on cells of multiple lineages.
      However, these caveats aside, the potential for understanding and correcting a
      disease that robs infants at so early an age of the potential for a normal life
      will continue to make these exciting and extraordinarily rewarding pursuits.

PMID- 8298125
TI  - Clonal, nonconstitutional rearrangements of the MLL gene in infant twins with
      acute lymphoblastic leukemia: in utero chromosome rearrangement of 11q23.
AB  - Rearrangements of chromosome band 11q23 are common in infant leukemias,
      comprising more than 70% of the observed chromosome abnormalities in children
      less than 1 year of age. The MLL gene, which is located at the 11q23 breakpoint
      in infant, childhood, and adult acute leukemias, has been cloned and has homology
      to the Drosophila trithorax gene. The breakpoints in MLL are restricted to an 8.3
      kilobase pair (kb) region of the gene that is involved in translocations with as
      many as 29 other chromosomal regions in a number of phenotypically distinct acute
      leukemias. We have detected an identical, clonal, nonconstitutional rearrangement
      of the MLL gene in peripheral blood cells from a pair of female infants twins
      with acute lymphoblastic leukemia (ALL) and a t(11;19)(q23;p13.3). The detection
      of nonidentical IGH rearrangements suggests that the MLL rearrangement took place
      in a B-cell precursor or hematopoietic stem cell in one twin which was
      transferred in utero to the other fetus resulting in ALL with an identical
      aneuploid karyotype in both infants. We speculate that the other MLL-related
      infant leukemias may also develop in utero, and that the rearrangements may occur
      consistently in stem cells or early precursor cells, accounting for the frequency
      of mixed-lineage leukemia in infants.

PMID- 8298126
TI  - Erythroid failure in Diamond-Blackfan anemia is characterized by apoptosis.
AB  - Programmed cell death, also known as apoptosis, is frequently initiated when
      cells are deprived of specific trophic factors. To investigate if accelerated
      apoptosis contributes to the pathogenesis of Diamond-Blackfan anemia (DBA), a
      rare pure red blood cell aplasia of childhood, we studied the effect of
      erythropoietin (epo) deprivation on erythroid progenitors and precursors from the
      bone marrow of DBA patients as compared with hematologically normal controls.
      Apoptosis in response to epo deprivation was evaluated by enumeration of colony
      forming unit-erythroid (CFU-E)- and burst-forming unit-erythroid (BFU-E)-derived
      colonies in plasma clot semisolid culture and by the identification of typical
      DNA oligosomes by gel electrophoresis from marrow mononuclear cells in liquid
      culture. In all DBA patients there was a marked decrease in CFU-E- and BFU-E
      derived colony formation compared with normal controls at comparable time points
      of epo deprivation, with a complete loss of CFU-E-derived colonies in semisolid
      culture by 9 hours of epo deprivation versus 48 hours in controls. The BFU-E
      derived colony response to epo deprivation displayed a similar pattern of
      decrement. Apoptotic changes assessed by the presence of characteristic DNA
      fragmentation began in the absence of epo deprivation and were readily detected
      within 3 hours of epo deprivation in DBA cultures versus 9 hours in controls. We
      conclude that DBA is characterized by accelerated apoptosis as measured by the
      loss of erythroid progenitor clonogenicity and increased progenitor and precursor
      DNA fragmentation leading to the formation of characteristic oligosomes,
      consistent with an intrinsic erythroid-progenitor defect in which increased
      sensitivity to epo deprivation results in erythroid failure.

PMID- 8298127
TI  - Retinoic acid downmodulates erythroid differentiation and GATA1 expression in
      purified adult-progenitor culture.
AB  - All-trans retinoic acid (RA) is an important morphogen in vertebrate development,
      a normal constituent in human adult blood and is also involved in the control of
      cell growth and differentiation in acute promyelocytic leukemia. We have examined
      the effects of RA on normal hematopoiesis by using early hematopoietic progenitor
      cells (HPC) stringently purified from adult peripheral blood. In clonogenetic
      fetal calf serum-supplemented (FCS+) or -nonsupplemented (FCS-) culture treated
      with saturating levels of interleukin-3 (IL-3) granulocyte-macrophage colony
      stimulating factor (GM-CSF) and erythropoietin (Ep) (combined with c-kit ligand
      in FCS(-)-culture conditions), RA induces a dramatic dose-dependent shift from
      erythroid to granulomonocytic colony formation, the latter colonies being
      essentially represented by granulocytic clones. This shift is apparently not
      caused by a recruitment phenomenon, because in FCS+ culture, the total number of
      colonies is not significantly modified by RA addition. In FCS- liquid-suspension
      culture supplemented with saturating Ep level and low-dose IL-3/GM-CSF, adult HPC
      undergo unilineage erythropoietic differentiation: Here again, treatment with
      high-dose RA induces a shift from the erythroid to granulocytic differentiation
      pathway. Studies on RA time-response or pulse treatment in semisolid or liquid
      culture show that early RA addition is most effective, thus indicating that early
      but not late HPC are sensitive to its action. We then analyzed the expression of
      the master GATA1 gene, which encodes a finger transcription factor required for
      normal erythroid development; addition of RA to HPC stimulated into unilineage
      erythropoietic differentiation in liquid culture caused a virtually complete
      inhibition of GATA1 mRNA induction. These results indicate that RA directly
      inhibits the erythroid differentiation program at the level of early adult HPC,
      and may lead to a shift from the erythroid to granulocytic differentiation
      pathway. This phenomenon is correlated with inhibition of GATA1 induction in the
      early stages of erythropoietic differentiation.

PMID- 8298128
TI  - The macrocyclic lactone protein kinase C activator, bryostatin 1, either alone,
      or in conjunction with recombinant murine granulocyte-macrophage colony
      stimulating factor, protects Balb/c and C3H/HeN mice from the lethal in vivo
      effects of ionizing radiation.
AB  - We have examined the in vivo radioprotective effects of the macrocyclic lactone
      protein kinase C (PK-C) activator, bryostatin 1, administered either alone or in
      conjunction with recombinant murine granulocyte-macrophage colony-stimulating
      factor (rmGM-CSF), in Balb/c and C3H/HeN mice subjected to lethal total body
      irradiation (TBI). When administered alone on a divided dose schedule (24 hours
      and 30 minutes before TBI), rmGM-CSF (20 micrograms/kg) was ineffective in
      increasing survival in either strain. However, in Balb/c mice, bryostatin 1 alone
      (1 microgram) permitted the long-term survival (60 days) of 70% of the animals
      following TBI, and 80% when administered in conjunction with rmGM-CSF. Bryostatin
      1 administered alone according to this schedule exerted minimal radioprotective
      effects in C3H/HeN mice, but, when combined with a subeffective dose of rmGM-CSF,
      allowed 50% of the animals to survive. Treatment of Balb/c mice with bryostatin 1
      administered as a single dose 4 hours before TBI resulted in a 20% survival rate,
      and 45% when administered with rmGM-CSF; corresponding values for the C3H/HeN
      strain were 60% and 40%, respectively. Lastly, the survival rates of Balb/c mice
      treated with bryostatin 1 administered as a single dose 4 hours following TBI was
      20%, and 25% with rmGM-CSF; corresponding values were 50% and 25% for C3H/HeN
      mice. These findings indicate that the PK-C activator bryostatin 1 exhibits
      intrinsic in vivo radioprotective effects in lethally irradiated Balb/c and
      C3H/HeN mice, and may, under some circumstances, augment the radioprotective
      capacity of rmGM-CSF. They also underscore the critical role that strain
      differences and scheduling considerations play in determining the in vivo
      radioprotective capacity of bryostatin 1, as well as its interactions with rmGM
      CSF.

PMID- 8298129
TI  - Isolation and characterization of a TATA-less promoter for the human beta 3
      integrin gene.
AB  - Proper expression of the human platelet fibrinogen receptor is necessary for the
      maintenance of normal hemostasis. This receptor is formed by the heterodimer
      alpha IIb beta 3, a prototypic member of the integrin family of adhesive
      molecules. beta 3 is also expressed in other tissues with alpha v as the
      vitronectin receptor. It was not possible to study the basis for tissue-specific
      expression of this gene, because the beta 3 gene promoter had not been isolated
      previously. We have now isolated a 6.0-kb human genomic DNA fragment containing
      2.0 kb of sequence 5' to the beta 3 ATG start codon. This clone also contains
      sequence encoding the signal peptide of the immature beta 3 protein and 3.0 kb of
      3' intronic sequence. Primer extension and RNase protection studies of poly A+
      RNA from a human erythroleukemia (HEL) cell line indicated a major transcription
      start site 30 bp upstream of the ATG start codon. In an orientation-dependent
      manner, a 584-bp fragment 5' to the start codon promotes expression of the
      chloramphenicol acetyl transferase (CAT) reporter gene in K562 cells. CAT
      expression from this beta 3 promoter is fivefold above expression from a
      "promoter-less" control CAT construct. This beta 3 promoter lacks TATA and CAAT
      cis-acting elements, but there are two Sp1 sites flanking the transcription start
      site. Other potential transcription factor binding sites are also identified.
      Phorbol esters (TPA), which increase beta 3 transcription in K562 cells,
      stimulated transcription from the 584-bp 5' beta 3 region. The isolation of this
      beta 3 promoter region should permit a more detailed analysis of its
      transcriptional regulation.

PMID- 8298130
TI  - A novel nucleotide-based thrombin inhibitor inhibits clot-bound thrombin and
      reduces arterial platelet thrombus formation.
AB  - A novel thrombin inhibitor based on single-stranded (ss) deoxynucleotides with
      the sequence GGTTGGTGTGGTTGG (thrombin aptamer) has been recently discovered. In
      this study, we tested its efficacy in inhibiting clot-bound thrombin activity and
      platelet thrombus formation in an ex vivo whole artery angioplasty model. The
      thrombin aptamer showed a specific dose-dependent inhibition of thrombin-induced
      platelet aggregation (0.5 U/mL) in human platelet-rich plasma, with an IC50 of
      approximately 70 to 80 nmol/L. In an in vitro clot-bound thrombin assay system,
      heparin, used at clinically relevant concentrations of 0.2 U/mL and 0.4 U/mL, was
      ineffective in inhibiting clot-bound thrombin (6.5% and 34.9% inhibition at 0.2
      U/mL and 0.4 U/mL, respectively). In contrast, the thrombin aptamer at an
      equivalent anticoagulant concentration inhibited clot-bound thrombin (79.7%
      inhibition). In an ex vivo whole artery angioplasty model, the thrombin aptamer
      markedly suppressed the generation of fibrinopeptide A (FPA), whereas heparin at
      2 U/mL was ineffective. Compared with a scrambled ssDNA control, the thrombin
      aptamer reduced platelet deposition by 34.5% +/- 5% (mean +/- SEM, n = 4, P =
      .09) at low shear rates (approximately 200 s-1) and 61.3% +/- 11% (mean +/- SEM,
      n = 4, P = .05) at high shear rates (approximately 850 s-1). Thrombin aptamers
      based on ssDNA molecules represent a new class of thrombin inhibitors with potent
      anticoagulant and antithrombotic properties.

PMID- 8298131
TI  - Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys-155 in
      the second epidermal growth factor-like domain of protein S.
AB  - A 29-year-old female patient with heterozygous congenital protein S deficiency
      suffering from thrombotic disease had normal levels of both total and free
      protein S antigen (70% and 65%, respectively), but low cofactor activity (31%)
      for activated protein C, indicating that she had a variant of protein S, protein
      S Tokushima. Western blotting using the polyclonal anti-protein S antibody showed
      that approximately half of the patient's protein S appeared to be the variant
      with a higher molecular weight than normal protein S. The partially purified
      variant protein S bound neither to the monoclonal antibody recognizing calcium
      dependent conformation of protein S nor to the antibody recognizing the thrombin
      sensitive domain of protein S. Among the exons from II to XV of the patient's
      protein S gene encoding from the NH2-terminal end to the COOH-terminal end of
      protein S, only one missense mutation (A to G) was found in exon VI of the
      protein S alpha-gene, which results in amino acid substitution of Glu(GAG) for
      Lys-155(AAG) in the second epidermal growth factor-like domain of protein S. The
      recombinant protein S Tokushima expressed in BHK cells had a slightly higher
      molecular weight than the recombinant normal one, did not bind to the antibody
      specific for the thrombin-sensitive domain, and did not show the cofactor
      activity. These findings suggest that the protein S Tokushima molecule is
      structurally and functionally a variant of protein S, and that this variant
      protein S is the cause of severe thrombosis in this patient.

PMID- 8298132
TI  - Glycocalicin: a new assay--the normal plasma levels and its potential usefulness
      in selected diseases.
AB  - Platelet glycocalicin (GC) is the extramembranous portion of GPIb alpha that can
      be rapidly cleaved by enzymes such as calpain, plasmin, trypsin, elastase, etc.
      Quantitative cleavage will ultimately result in an acquired Bernard-Soulier-like
      bleeding disorder, and circulating GC may act as a potential inhibitor of
      platelet adhesion. We have developed and standardized a new enzyme-linked
      immunosorbent assay (ELISA), which uses two monoclonal antibodies (mAbs), both of
      which bind to the amino-terminal 45-kD fragment of GC and inhibit platelet-von
      Willebrand interactions and the streptavidin-biotin system. First, the
      methodology was evaluated and standardized with special emphasis on the
      anticoagulant and the inhibitors (EDTA, prostaglandin E1 [PGE1], aprotinin, N
      ethyl-maleimide), the mode of high-speed centrifugation (to avoid platelet
      microparticles), and the standards used (purified GPIb and GC). This assay was
      then used to analyze the GC levels of healthy subjects (2.04 +/- 0.46
      micrograms/mL) and of patients with selected diseases. The results of patients
      with aplastic anemia and thrombocytosis confirmed that GC levels are clearly
      dependent on the platelet count, which was the basis for the introduction of the
      GC index, the standardization of GC for a platelet count of 250 x 10(9)/L. The GC
      index discriminates reliably patients with active immune thrombocytopenic purpura
      from those in remission. GC levels are elevated in patients on hemodialysis (3.62
      +/- 0.75 micrograms/mL, P < .001). The high GC index (6.93 +/- 4.21, P < .001) in
      cirrhosis patients suggests an increased platelet turnover and/or abnormal
      proteolysis. In contrast to other groups, we have not found that recombinant
      tissue plasminogen activator (rtPA) treatment of patients with myocardial
      infarction increases GC levels. However, concentrations are elevated in leukemia
      and the highest levels found are approximately 40 micrograms/mL. These studies
      suggest that GC is a useful platelet marker in certain diseases, which directly
      reflects platelet damage and possibly platelet dysfunction.

PMID- 8298133
TI  - Patterns of cytokine gene expression in infectious mononucleosis.
AB  - Primary infection with Epstein-Barr virus (EBV) may arise as infectious
      mononucleosis (IM) in adolescents and young adults. Morphologically, IM-affected
      lymphoid tissue is characterized by expanded interfollicular areas with formation
      of atypical lymphoid blasts. It is assumed that morphology and clinical
      presentation of IM are related to characteristic patterns of cytokine production
      by EBV-infected and reactive cells. We studied IM tonsils of eight patients and
      six normal tonsils with a double in situ hybridization procedure using [35S]
      labeled RNA probes specific for various cytokines and digoxigenin-labeled probes
      for the detection of the nuclear EBV encoded RNA transcripts, EBER 1 and 2. All
      of the IM cases displayed the same distinct cytokine gene expression pattern.
      When compared with interfollicular areas of normal tonsils, expression of
      lymphotoxin (LT), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
      and IL-1 beta, but not IL-8 or IL-1 alpha was strongly enhanced in
      interfollicular areas in IM tonsils. LT was expressed predominantly by EBV
      infected cells. TNF-alpha transcripts were also present in EBV-infected cells,
      although in smaller proportions. IL-6 specific signals were only found in few EBV
      infected cells. IL-1 alpha-, IL-1 beta-, and IL-8-specific signals were not
      observed in EBV-infected cells, but were present at high signal intensity in many
      cells within and around foci of EBV-infected cells (IL-1 beta), next to areas of
      necrosis (IL-8, IL-1 beta), or in epithelial cells (IL-1 alpha). These data
      suggest that EBV infection in form of IM results in induction of specific sets of
      cytokine genes in EBV-infected and in neighboring EBV-negative cells contributing
      to the characteristic morphology and cellular arrangement of the lesion as well
      as the clinical presentation.

PMID- 8298134
TI  - Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor
      dependent and T-cell receptor-independent thymocyte proliferation.
AB  - The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) are not
      confined to cells of the myeloid lineage. GM-CSF has been shown to have effects
      on mature T cells and both mature and immature T-cell lines. We therefore
      examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM
      CSF also affected normal immature T lymphocytes. The studies presented here
      indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)
      mediated proliferation of unseparated thymocyte populations. To identify the GM
      CSF responsive cell type, thymic AC and T cells were examined for GM-CSF
      responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte
      proliferation appears to be mediated via augmentation of AC function, and not via
      direct effects on mature single-positive (SP) thymocytes. Enriched double
      negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF
      induced the proliferation of adult and fetal DN thymocytes in an AC-independent
      and TCR-independent single-cell assay. Thus, in contrast to the SP thymocytes, a
      DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may
      play a direct role in the expansion of DN thymocytes and an indirect role in the
      expansion of SP thymocytes.

PMID- 8298135
TI  - H- and L-rich ferritins suppress antibody production, but not proliferation, of
      human B lymphocytes in vitro.
AB  - The effect of human spleen(L-rich) and heart(H-rich) ferritins on the
      proliferation and differentiation of human B lymphocytes was studied in
      comparison with that of holo- and apo-transferrins. Ferritins rich in H and L
      chain, as well as the transferrins, did not inhibit the proliferative response of
      resting and activated B cells stimulated with polyclonal B-cell mitogen,
      Staphylococcus aureus Cowan strain I. In contrast, the ferritins, but not the
      transferrins, clearly suppressed the antibody production by B blasts in T-cell
      independent as well as T-cell-dependent system. Kinetic study showed that
      inhibitory action of ferritins on immunoglobulin (Ig) production was caused at an
      early stage of B-cell differentiation. The cytoplasmic Ig-containing cells
      decreased in proportion to the reduction of Ig secretion. The evidence that
      ferritin inhibited Ig synthesis of Epstein-Barr virus-transformed human B
      lymphoblastoid cell line also supported the idea that the effect of ferritin was
      directed toward the antibody-producing B lymphocytes. The molecular analysis
      showed that the inhibitory effect of ferritin was regulated at the
      transcriptional level of the Ig generation signal. Our results suggest that H-
      and L-rich ferritins exert their inhibitory action on the differentiation of B
      cells maturing into Ig-producing cells.

PMID- 8298136
TI  - Identification of masked polycythemia vera from patients with idiopathic marked
      thrombocytosis by endogenous erythroid colony assay.
AB  - We used the methylcellulose-culture technique to determine the utility of the
      erythroid progenitor growth in vitro from nonadherent T-depleted bone marrow and
      peripheral blood cells in distinguishing polycythemia vera (PV) from essential
      thrombocythemia. Thirty patients with PV (group A) and 30 patients who presented
      with idiopathic marked thrombocytosis with platelet count greater than 1,000 x
      10(9)/L and a normal or reduced hemoglobin (Hb) level (group B) were studied at
      initial presentation. Endogenous (erythropoietin-independent) erythroid colonies
      (EEC) were found in all patients in group A and 13 in group B. The numbers of EEC
      were comparable between patients in group A and the 13 patients with EEC in group
      B, 11 of whom with initial Hb levels ranging between 6.4 g/dL and 12.6 g/dL were
      found to have PV 2 to 45 months after initial evaluation. The number of EEC did
      not correlate with the time to the progression of polycythemia, whereas
      myelosuppression delayed the subsequent development of PV. Of the two patients
      with EEC in group B who did not develop PV, both received chemotherapy soon after
      presentation, which might preclude the evidence of polycythemia evolution. None
      of the other patients in group B who did not form EEC developed PV with a median
      follow-up of 24 months. This study indicates that the assessment of EEC in bone
      marrow or blood is helpful in early identification of PV or prediction of
      polycythemia evolution in patients with marked thrombocytosis in whom
      polycythemia has been initially masked or anemia is present.

PMID- 8298137
TI  - Plasma zinc level and thymic hormone activity in young cancer patients.
AB  - It has been reported that in many neoplastic diseases, including leukemia,
      alterations in plasma zinc levels may frequently occur, although the causes for
      such alterations have yet to be clearly defined. Since zinc is required to induce
      biological activity to thymulin (Zn-FTS), a biochemical defined thymic hormone,
      and marginal zinc deficiencies may prevent its peripheral biological activation,
      we investigated the plasma level of zinc and of both active thymulin (Zn-FTS) and
      total zinc saturable thymulin (Zn-FTS + FTS) in 91 young patients affected by
      acute lymphoblastic leukemia (ALL) at various stages of the disease. It was
      discovered that the plasma zinc level was reduced at the onset and relapse,
      whereas in complete remission and in off-therapy it was in the normal range.
      Total zinc-saturable thymulin concentration did not change during the disease,
      whereas the active fraction was reduced at the onset and in relapse when compared
      with values observed in the other stages of the disease or in healthy controls.
      These data suggest that zinc plasma deficiency is present in ALL patients at the
      onset and during relapse, and that such a deficiency causes a decrease in the
      activity of thymulin despite a nearly normal production by the thymus. An
      impairment of peripheral immune efficiency in ALL patients is commonly found. The
      existence of positive correlations between zinc or active thymulin and peripheral
      immunological parameters (phytohemagglutinin [PHA] and concanavalin A [ConA]) at
      various stages of the disease suggests a link between derangement of peripheral
      immune function, thymic hormone activity, and zinc failure. These findings,
      considered together, suggest the possibility of a carefully controlled clinic
      trial with zinc in ALL patients at the onset and in relapse even in the light of
      in vitro ineffectiveness of physiological zinc or thymulin concentrations on the
      duplicative index of human lymphoblastoid cells.

PMID- 8298138
TI  - T-cell receptor gene rearrangement in T-cell large granular leukocyte leukemia:
      preferential V alpha but diverse J alpha usage in one of five patients.
AB  - T-gamma lymphoproliferative disease (T-gamma LPD) is a chronic disorder of mature
      T cells that is associated with neutropenia and autoimmune phenomena. Although
      the progression of the lymphoproliferation is indolent, it is often associated
      with a monoclonal proliferation of T-cell-type large granular lymphocytes (LGL)
      that manifest multiple in vitro suppressor and cytotoxic activities. We
      considered the possibility that the granulocytopenia or anemia might represent an
      autoimmune disorder mediated by the monoclonal LGL via T-cell receptor (TCR)
      recognition of an antigen involved in hematopoiesis. Therefore, in an effort to
      characterize the usage of the TCR alpha- and beta-chain genes in patients with T
      gamma LPD, we cloned and sequenced TCR alpha- and beta-chain mRNAs derived from
      the T-cell type LGL of five patients. The five patients studied did not use a
      common V alpha nor a common J alpha segment. However, an unusual finding was
      observed in one of the patients where the occurrence of a single variable
      diversity-junctional (VDJ) rearrangement of the beta chain confirmed the
      monoclonal origin of the LGL proliferation. In accord with this evidence for
      monoclonality, many of the cells studied used a common V alpha (V alpha 19.1). In
      contrast to this common V alpha usage, there was a marked diversity of the J
      alpha segments and N-region addition that were associated with the V alpha 19.1
      segment. This pattern of common V alpha usage associated with different N and J
      alpha segments suggests an immune-mediated selection process affecting the TCR
      alpha chain occurring after the transformation event that established the clone.
      We suggest that the T-cell-type LGL malignant clone might have developed
      autoreactivity conferred by the selected TCR alpha chain and that this
      autoreactivity might be implicated in this patient's anemia.

PMID- 8298139
TI  - Regression of experimental Burkitt's lymphoma induced by Epstein-Barr virus
      immortalized human B cells.
AB  - Epstein-Barr virus (EBV)-immortalized human B cells survive only transiently when
      injected subcutaneously into athymic mice, whereas Burkitt's lymphoma cells give
      rise to progressively growing subcutaneous tumors. In this study, we tested
      whether these Burkitt's tumors could be induced to regress via a bystander effect
      induced by EBV-immortalized B cells. Simultaneous inoculation of EBV-immortalized
      B cells and Burkitt's lymphoma cells in the same subcutaneous site resulted in
      tumors that regressed with necrosis and scarring. Similarly, simultaneous
      inoculation of EBV-immortalized B cells and Burkitt's lymphoma cells in separate
      subcutaneous sites resulted in regression of a proportion of the Burkitt's
      tumors. Furthermore, most of the established human Burkitt's tumors regressed
      with necrosis and scarring after intratumor inoculations with EBV-immortalized B
      cells. The EBV-immortalized B cells continued to exert this antitumor effect even
      when killed with irradiation. The experimental approach to Burkitt's lymphoma
      treatment described here exploits the ability of athymic mice to reject EBV
      immortalized B cells to target an effective antitumor response to malignant cells
      normally incapable of eliciting it.

PMID- 8298140
TI  - Identification of neutrophil gelatinase-associated lipocalin as a novel matrix
      protein of specific granules in human neutrophils.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is a novel 25-kD protein of
      human neutrophils, that is in part covalently complexed with neutrophil
      gelatinase. However, both NGAL and gelatinase exist mainly in forms not
      associated with each other. An explanation for this phenomenon might be that the
      unassociated proteins reside in different subcellular compartments. The aim of
      the present study was to determine the subcellular localization of NGAL. An
      enzyme-linked immunosorbent assay (ELISA) for NGAL was developed using specific
      anti-NGAL antibodies. The assay was applied on subcellular fractions of
      neutrophils obtained after centrifugation of a postnuclear supernatant on a two
      layer Percoll gradient. The distribution profile of NGAL was found to colocalize
      strictly with the distribution profile of lactoferrin. This was confirmed by
      immunogold double-labeling of frozen thin sections of neutrophils that showed a
      high degree of colocalization of NGAL and lactoferrin, and by exocytosis
      experiments, which showed lactoferrin, vitamin B12-binding protein, and NGAL to
      be similarly released upon stimulation. Therefore, NGAL is a novel matrix protein
      of specific granules and thus partly segregated from gelatinase, the major part
      of which is located in a separate compartment, the gelatinase granules. An ELISA
      specific for the NGAL/gelatinase complex was developed and the subcellular
      distribution and release of this complex was determined. The distribution and
      mobilization of the complex allowed us to confirm the existence of differentially
      mobilized granule subpopulations among peroxidase negative granules.

PMID- 8298141
TI  - The receptor for urokinase-type plasminogen activator and urokinase is
      translocated from two distinct intracellular compartments to the plasma membrane
      on stimulation of human neutrophils.
AB  - The cellular receptor for urokinase-type plasminogen activator (uPAR) binds pro
      urokinase (pro-uPA) and facilitates its conversion to enzymatically active
      urokinase (uPA). uPA in turn activates surface-bound plasminogen to plasmin, a
      process of presumed importance for a number of biologic processes including cell
      migration and resolution of thrombi. We have previously shown that uPAR is
      expressed on the plasma membrane of circulating neutrophils, and we now report
      that stimulation with phorbol myristate acetate (PMA), FMLP, or tumor necrosis
      factor-alpha results in a rapid increase in the expression of uPAR. This process
      is accompanied by an increased cell-associated plasminogen activation after
      preincubation of neutrophils with pro-uPA in vitro. By subcellular fractionation
      of unstimulated neutrophils, 50% of uPAR is recovered in fractions containing
      latent alkaline phosphatase, corresponding to an intracellular compartment of
      easily mobilizable secretory vesicles distinct from both primary and specific
      granules, whereas the remaining 50% of uPAR is associated with a compartment
      eluting close to the specific granules. In contrast, the ligand pro-uPA is
      primarily (approximately 80%) found in the specific granules, but small amounts
      of pro-uPA/uPA (approximately 20%) coelute with latent alkaline phosphatase.
      Stimulation of neutrophils with FMLP results in translocation of uPAR as well as
      of pro-uPA from the secretory vesicles, whereas stimulation with PMA is required
      to translocate material from specific granules. Flow cytometry of neutrophils
      saturated with exogenous diisopropyl fluorophosphate-uPA shows a large excess
      (approximately 90%) of unoccupied uPAR on resting as well as FMLP- and PMA
      stimulated neutrophils, suggesting a possible role for exogenous pro-uPA in
      providing neutrophils with a potential for plasminogen activation. These
      processes may be important for neutrophil extravasation and migration through
      extracellular matrix and for the contribution of neutrophils to resolution of
      thrombi.

PMID- 8298142
TI  - Hematopoietic repopulation of adult mice with beta-thalassemia.
AB  - Deletion of the murine beta-major globin gene on chromosome 7 causes a severe,
      hypochromic anemia in homozygous mice. We show that over 50% of the homozygous
      mice die either in utero or at birth. Mice heterozygous for the deletion have a
      slightly increased percentage of reticulocytes when compared with normal mice,
      but no clinical anemia. As a therapeutic measure, we transplanted 2 x 10(6)
      congenic genetically marked normal (+/+) marrow cells into adult homozygous and
      control heterozygous mice. Pretreatment with marrow ablative irradiation was
      required to obtain significant percentages of donor peripheral blood cells in the
      homozygous mice. Red blood cell (RBC) counts normalized after pretransplantation
      irradiation of thalassemic mice with nonlethal doses as low as 400 R. The
      thalassemic mice irradiated with 200, 400, and 600 R were erythroid-cell chimeras
      and remained so for at least 8 months posttransplantation, whereas those
      irradiated with 800 R had primarily donor erythrocytes by 8 weeks. RBC
      replacement preceded non-erythroid cell replacement at 200, 400, and 600 R. This
      selective repopulation was more noticeable in the thalassemic mice than in
      control mice. The fact that chimeric mice are cured, coupled with a recent
      observation by others that erythroid replacement occurs in unirradiated newborn
      thalassemic mice, suggest transplantation therapy in utero might augment
      survival.

PMID- 8298143
TI  - Discrepancy between IIA phenotype and IIB genotype in a patient with a variant of
      von Willebrand disease.
AB  - Type IIA and IIB von Willebrand disease (vWD) result from qualitative
      abnormalities of von Willebrand factor (vWF) characterized by an absence in
      plasma of high molecular weight vWF multimers and an abnormal reactivity of vWF
      towards platelet glycoprotein (GP) Ib, which is decreased in type IIA and
      increased in type IIB. In this report, we describe the case of a patient having a
      IIA vWD phenotype associated with an intermittent thrombocytopenia atypical in
      this subtype but observed in type IIB vWD. The patient plasma vWF showed an
      absence of high molecular weight and intermediate multimers and had a decreased
      binding capacity to GPIb. The affinity of botrocetin was normal for plasma vWF
      from the propositus. Analysis of the propositus vWF gene showed the presence of a
      substitution Val 551 to Phe of the mature vWF subunit. This mutation is localized
      within a 509-695 disulphide loop of the vWF that plays an important role in the
      binding to GPIb and is where most of the molecular defects described so far were
      associated with type-IIB vWD. We have reproduced the Val 551 Phe substitution
      onto the vWF cDNA, expressed it in COS-7 cells, and performed structural and
      functional analysis of the mutant recombinant protein (rvWFPhe 551). The rvWFPhe
      551 had a normal multimeric structure and showed the capacity to spontaneously
      interact with GPIb. Botrocetin had a decreased affinity for rvWFPhe 551. In
      conclusion, the Val 551 Phe mutation modifies the affinity of vWF for platelet
      GPIb, as does a type IIB mutation, and may be responsible for the
      thrombocytopenia of the patient and the clearance of the high molecular weight
      and intermediate-sized multimers of vWF from the plasma. The study of the rvWFPhe
      551 has confirmed the discrepancy between the IIA phenotype and the IIB genotype
      of the patient.

PMID- 8298144
TI  - Acute B-lineage lymphoid malignancy after interferon therapy for chronic viral
      hepatitis.

PMID- 8298145
TI  - Natural killer cell numbers and activity in patients with chronic autoimmune
      thrombocytopenic purpura.

PMID- 8298146
TI  - Serum NCAM: a potential new prognostic marker for multiple myeloma.

PMID- 8298147
TI  - Interferon-alpha 2a treatment in a pregnant woman with essential thrombocythemia.

PMID- 8298148
TI  - Response criteria with fludarabine therapy in chronic lymphocytic leukemia.

PMID- 8298149
TI  - The mandibular overdenture supported by implants in the anterior symphysis: a
      prescription for implant placement and bar-prosthesis design.

PMID- 8298150
TI  - Synthetic bone material as particulate matter in conjunction with endosseous
      implants.

PMID- 8298151
TI  - The latest developments in blade implant clinical applications.

PMID- 8298152
TI  - The laboratory partner in the implant team approach.

PMID- 8298153
TI  - Effective uses of radiographs for implant placements--panographs, cephalograms,
      CT scans.

PMID- 8298154
TI  - Stabilizing root-form implants in the compromised maxillary sinus areas.

PMID- 8298155
TI  - Anterior maxillary single tooth implant demands precise coordination and
      planning.

PMID- 8298156
TI  - How to motivate, inform dental implant patients on home care.

PMID- 8298157
TI  - Distinguishing between failing metal root-form implants and complete implant
      failures.

PMID- 8298158
TI  - The single-tooth replacement and the partially-edentulous arch: a prosthodontics
      implant approach.

PMID- 8298159
TI  - Calcium sulfate is a safe, resorbable barrier adjunct to implant surgical
      procedures.

PMID- 8298160
TI  - Combining implants and natural teeth within the same arch.

PMID- 8298161
TI  - Gastrin antagonists in the treatment of gastric cancer.
AB  - The polypeptide hormone, gastrin, is known to promote both the in vitro and in
      vivo growth of human gastric cancer. This proliferative activity has been shown
      to be mediated by high affinity, membrane-associated receptors. This has led to
      the development of agents with the ability to antagonise gastrin receptor
      binding, which have been evaluated for their potential clinical value. Other anti
      gastrin therapies have been investigated. As gastrin may act as an autocrine
      mediator of gastric tumor cell proliferation, anti-secretory agents have been
      evaluated, as have agents which induce the production of neutralising anti
      gastrin antibodies in situ.

PMID- 8298162
TI  - Isolation of a mitomycin-resistant human lung adenocarcinoma cell subline to
      investigate the modulation by sodium butyrate of cell growth and drug resistance.
AB  - We developed a mitomycin C (MMC)-resistant human lung adenocarcinoma cell
      subline, SPC-A1/DM4, from cloned SPC-A1/D13 parent cells by 1 h exposures to
      escalating concentrations of the drug over 17 months. A 5.9-fold resistance to
      MMC and a 3.8-fold cross-resistance to cisplatin were present in resistant cells
      compared with parent cells. This phenotype was stable in the absence of drug
      exposure for at least 6 months. Sodium butyrate (NaBu), a widely used
      differentiating agent, was shown to inhibit cell proliferation in a dose
      dependent manner, with the cytostatic concentration of 2 mM. This NaBu-induced
      growth inhibition was reversible. However, SPC-A1/DM4 cells, after recovery from
      the cytostasis induced by 2 days treatment with 2 mM NaBu, became 2-fold more
      sensitive to MMC than the cells not exposed to the agent. Meanwhile, the
      cisplatin response of these treated cells reached a level comparable to the
      parent cells. This modulation by NaBu of drug resistance could be retained for at
      least 1 month. Treatment with 2 mM NaBu for 2 days caused inhibition of DNA
      synthesis and accumulation of cells in the G1 and G2/M-phases of the cell cycle.
      Correlated with these were a marked increase of protein content in these cell
      subpopulations and an enhanced RNA synthesis. In addition, NaBu-treated cells
      acquired development of endoplasmic reticulum and accumulated lipid droplets.
      These morphological alterations were accompanied by a significant decrease in the
      ratio of nuclear to cytoplasmic areas. These findings suggest that NaBu is
      potentially useful in the treatment of drug-resistant non-small cell lung cancer.
      Information about the NaBu-induced phenotypic alterations may offer a clue to the
      understanding of its long-term effect on drug resistance.

PMID- 8298163
TI  - Mitotic index and cell proliferation kinetics for identification of
      antineoplastic activity.
AB  - The mitotic index (MI) and cell proliferation kinetics (CPK) of human blood
      lymphocyte cultures were determined to evaluate the effects of six antineoplastic
      drugs with well known cytostatic activity: cisplatin, melphalan, bleomycin,
      methotrexate, 5-fluorouracil and 6-mercaptopurine. All six drugs showed a clear
      effect on the inhibition of MI. The first three drugs interact directly with DNA
      showing a dose-related retardation of CPK. Methotrexate, 5-fluorouracil and 6
      mercaptopurine, which act on ribonucleotide biosynthesis, showed no significant
      effects on CPK. The results suggest that CPK and MI measurements are useful for
      the prescreening of drugs with potential cytostatic activity.

PMID- 8298164
TI  - Suppression of mammary tumors by oral administration of 1-(2-tetrahydrofuryl)-5
      fluorouracil in combination with uracil in SHN virgin mice.

PMID- 8298165
TI  - Modulation of the shedding of a rat tumor-associated antigen by growth regulation
      and anti-cancer drugs.
AB  - CE7 antigen is shed from A3 cell surfaces by cells grown in medium containing a
      sufficient (10%) amount of fetal calf serum (FCS), but shedding of the antigen
      decreases with a decrease in FCS content in the culture medium. However, the
      cells contain similar amounts of antigen as evidenced by Western blotting,
      indicating that low FCS levels interfere with antigen shedding but not antigen
      synthesis. Antigen expression by A3 cells treated with mitomycin C gradually
      shifted from negative to a strong positive with time, and on day 2, two peaks
      corresponding to negative and positive cells within the population can be
      observed. In contrast, A3 cells treated with bleomycin and cyclophosphamide
      shifted as a whole from negative to weakly positive. When A3 cells in media
      containing 10% FCS were incubated at 4 degrees C, although the cells did not
      proliferate, antigen expression could not be detected by flow cytometry.

PMID- 8298166
TI  - The cytotoxicity of N-substituted diphenimides and 6,7-dihydro-5H
      dibenz[c,e]azepines.
AB  - N-substituted diphenimides and 6,7-dihydro-5H-dibenz[c,e]azepines demonstrated
      significant cytotoxic activity against the growth of murine and human cells.
      These derivatives were active against leukemias, carcinomas and sarcomas.
      Different derivatives with N-substitutions showed specific activity against the
      growth of several tumor types. These agents inhibited L1210 leukemia IMP
      dehydrogenase and PRPP amido transferase activities; this was reflected in the
      inhibition of purine and DNA synthesis. Other sites inhibited to a minor degree
      by these agents included DNA polymerase alpha, r- and tRNA polymerases,
      ribonucleoside reductase, dihydrofolate reductase, pyrimidine synthesis, and
      nucleoside kinase. d(NTP) pool levels were reduced after 24 h incubation with
      these derivatives. L1210 DNA strand scission was evident after drug treatment.

PMID- 8298167
TI  - Gemcitabine: novel combination of efficacy and tolerability.

PMID- 8298168
TI  - Delayed-onset hearing loss in respiratory distress syndrome: case reports.
AB  - The pre-, peri-, and postnatal histories for two infants who suffered respiratory
      distress syndrome (RDS) are presented. Each infant was diagnosed with RDS within
      24 hours after birth, placed on high-frequency jet ventilation, and passed
      auditory brainstem response (ABR) screening prior to hospital discharge. Both
      infants were enrolled in a neonatal follow-up program with no report of hearing
      loss during the first year of life. At 2.5 years of age, each infant was found to
      have severe-to-profound sensorineural hearing loss. Neither infant suffered
      kidney failure, rubella, cytomegalovirus, or genetic involvement. Audiologic
      monitoring after hospital discharge was not performed because each infant passed
      the ABR screen. Thus, the date of onset and/or progression of hearing loss are
      unknown. Until additional research findings are available, we recommend that the
      hearing of any infant diagnosed with RDS be monitored frequently until 3 years of
      age.

PMID- 8298169
TI  - False negative auditory brainstem response findings in vestibular schwannoma:
      case reports.
AB  - The false negative rate of the auditory brainstem response (ABR) for the
      detection of vestibular schwannoma (VS; acoustic neuroma) has been reported to
      range from 2 to 9 percent. The introduction of magnetic resonance with gadolinium
      contrast (Gd MRI) may be expected to raise the false negative rate, because
      smaller tumors can now be detected. We present two cases that illustrate some of
      the complex issues raised by the detection of small asymptomatic VS by Gd MRI
      that were missed by ABR. The role of ABR testing in the diagnosis and management
      of VS remains well established and will continue to evolve.

PMID- 8298170
TI  - Progression of hearing loss following the completion of chemotherapy and
      radiation therapy: case report.
AB  - There have been scattered accounts reported in the oncology literature of
      progressive hearing loss following the conclusion of chemotherapy. In this case
      study, we report the audiologic findings of such a case. These data underscore
      the need for post-therapy monitoring in cases where threshold shifts are
      discovered during the course of drug administration.

PMID- 8298171
TI  - Insular stroke causing unilateral auditory processing disorder: case report.
AB  - This case presentation describes a patient with a strategically placed lesion
      involving the right insula and adjacent white matter. The most remarkable finding
      associated with this case is the presence of a unilateral auditory processing
      disorder when presenting speech materials to the left ear. Intervention for this
      patient is described in addition to a discussion of possible explanations for the
      unique pattern of auditory dysfunction.

PMID- 8298172
TI  - Sudden hearing loss in multiple sclerosis: case report.
AB  - This case illustrates the occurrence of a sudden hearing sensitivity loss that,
      in all likelihood, was the result of brainstem disorder resulting from multiple
      sclerosis (MS). Subject LD is a young woman who developed a sudden hearing loss
      while hospitalized for exacerbation of symptoms related to multiple sclerosis. By
      her own report, she had normal hearing in her left ear at the time of
      hospitalization. Four days after admission, she developed a hearing loss in her
      left ear, accompanied by roaring tinnitus and fullness. An audiologic evaluation
      revealed a substantial high-frequency sensitivity loss in the left ear. The
      combination of absent acoustic reflexes, depressed speech understanding, abnormal
      Bekesy audiometry, and an abnormal auditory brainstem response (ABR) was
      consistent with brainstem site of disorder. Over the next 2 weeks, hearing
      sensitivity recovered to within normal limits. This change in hearing sensitivity
      coincided with the recovery of acoustic reflexes, improvement in speech
      understanding, and partial recovery of the ABR.

PMID- 8298173
TI  - Electrocochleography with postural changes in perilymphatic fistula and Meniere's
      disease: case reports.
AB  - Perilymphatic fistula can be difficult to diagnose differentially prior to
      exploratory surgery. In this study, we investigated a new test technique in four
      case studies of subjects with perilymphatic fistula and compared our findings to
      results obtained in 20 normally hearing subjects with no history of vertigo and
      10 subjects with Meniere's disease. Recordings from an eardrum electrode were
      obtained with the subject in an upright position, after the subject had been
      lying in a horizontal position for 30 minutes with the test ear up and after 15
      minutes with the test ear down. Stimuli consisted of high level clicks and
      tonebursts. Neither the summating potential (SP) and action potential (AP)
      amplitudes nor the SP/AP amplitude ratio were significantly affected by postural
      change in either the normal or Meniere's disease group. The perilymphatic fistula
      subjects, in general, showed greater changes in the SP/AP, particularly for the
      6000 Hz tonebursts, than did the other two groups. More data will be needed to
      determine if these findings are consistent in a large population of perilymphatic
      fistula patients.

PMID- 8298174
TI  - Benign paroxysmal positioning vertigo with indeterminate cerebellar lesion: case
      report.
AB  - Of the numerous causes of dizziness, those that represent a life-threatening
      condition are rare. Physicians must guard against missing these rare but serious
      conditions while controlling the cost of the evaluation of patients who present
      with dizziness. This case study involving a 41-year-old female was written to
      illustrate the importance of systematic case history taking and of obtaining an
      ENG. The patient presented with classic symptoms of benign paroxysmal positioning
      vertigo (BPPV). The managing physician performed an MRI, which showed a
      cerebellar lesion. Results of a biopsy were negative. The patient's symptoms
      persisted, and she travelled to our clinic for further assessment. An ENG
      demonstrated a classic response to the Dix-Hallpike maneuvers, and a canalith
      repositioning maneuver was performed. The positioning dizziness resolved, and
      when contacted several months later, the patient stated she had remained
      asymptomatic.

PMID- 8298175
TI  - Otoacoustic emissions as a cross-check in pediatric hearing assessment: case
      report.
AB  - Audiologic assessment of infants and young children can be confounded by
      neurologic disorders or neuromaturational delays. In some cases, this results in
      an inability to assess hearing sensitivity by behavioral measures or by auditory
      evoked potentials. This case illustrates such an audiologic challenge. Subject DF
      was born with hydrocephaly, which was treated with repeated shunt surgeries and
      resulted in seizures and pervasive developmental delays. At 9 months of age, the
      child was tested by auditory brainstem response (ABR) measurement and found to
      have no response to sound. Believing that her child had hearing, DF's mother
      sought a second opinion. Results of an audiologic evaluation at 11 months of age
      showed no measurable behavioral responses in the sound field and an ABR
      abnormality that prevented prediction of hearing sensitivity. In contrast,
      sensitivity prediction by the acoustic reflex and results of both transient
      evoked and distortion-product otoacoustic emissions predicted normal peripheral
      hearing sensitivity. This case illustrates the usefulness of otoacoustic
      emissions as an additional cross-check measure in pediatric hearing assessment.

PMID- 8298176
TI  - Dynamic sensorineural hearing loss: implications for audiologists: case reports.
AB  - Although many persons with sensorineural hearing loss (SNHL) seeking hearing care
      do not have active ear disease, audiologists must appreciate the potentially
      dynamic and treatable nature of some etiologies of SNHL. This is particularly
      important now as audiologists are increasingly employed in private practice or
      other clinical settings that may serve as the point of entry for hearing care. In
      this paper, we review a variety of clinical entities affecting newborn infants,
      children, and adults that are associated with dynamic SNHL. Using a case report
      format, we illustrate treatment-related changes in SNHL, emphasizing the
      audiologist's role in patient management.

PMID- 8298177
TI  - Behavioral, electrophysiologic, and otoacoustic measures from a child with
      auditory processing dysfunction: case report.
AB  - This case was selected to highlight the importance of the test battery approach
      in the assessment of a child with auditory processing deficits. The utility of
      behavioral, electrophysiologic, acoustic immittance, and evoked otoacoustic
      emission procedures, as well as the problems associated with interpreting these
      multiple measures with differing results, is discussed. This case was confounded
      by the possibility that both peripheral and central auditory problems existed.
      The outcome stresses the importance of examining the results of multiple auditory
      measures in the determination of the site of lesion and habilitation strategies.

PMID- 8298178
TI  - X-linked mixed hearing loss with stapes fixation: case reports.
AB  - X-linked mixed hearing loss with stapes fixation is a congenital, recessive
      anomaly. The condition is characterized by progressive mixed hearing loss,
      reduced vestibular responses, and congenital fixation of the stapes with
      perilymph gusher encountered during surgical intervention. This paper describes
      the audiologic history of a family with two affected male children and one
      carrier female child. The need for early intervention and the challenges
      encountered in evaluation and management are discussed.

PMID- 8298179
TI  - Clinical and communication access through amplification for a medical student
      with severe hearing loss: case report.
AB  - This case report focuses on the communication difficulties of a 21-year-old
      medical student with severe-to-profound sensorineural hearing loss. The greatest
      difficulties reported by the patient were for stethoscope use and slide
      presentations in darkened rooms. Successful audiologic management was
      accomplished for this patient via use of a behind-the-ear (BTE) FM system for
      classroom use and a "homemade" amplified stethoscope that enabled him to hear
      diagnostic heart sounds for clinical use. The amplified stethoscope provided
      greater low-frequency gain for this patient than was available through other
      commercial units.

PMID- 8298180
TI  - Dehydration testing and the diagnosis of Meniere's disease: case report.
AB  - A 34-year-old female presented to our clinic with complaints of hearing loss,
      tinnitus, and severe rotational vertigo. A test battery including complete
      audiometric testing, auditory brainstem response (ABR) audiometry,
      electronystagmography (ENG), electrocochleography (ECoG), and dehydration testing
      was performed. Monitoring of hearing sensitivity, speech understanding, and ECoG
      responses following administration of a dehydrating agent were sensitive measures
      of cochlear function and confirmed the diagnosis of Meniere's disease. The
      induced changes also contributed to the therapeutic measures recommended.

PMID- 8298181
TI  - Simultaneous measurement of multiple membrane ATPases in microtiter plates.
AB  - An assay for activities of erythrocyte membrane-bound ATPases adapted from the
      autoanalyzer method of Raess and Vincenzi (1980a) is described in detail. Mg2+
      ATPase, Na+/K(+)-ATPase, Ca2+ ATPase, and calmodulin- (CaM) activated Ca2+
      ATPases were determined in microtiter plates. Total volume was 100 microL. Ten
      microliters of 0.75 mg/mL of red blood cells membranes were added to appropriate
      buffer in microtiter plates. Plates were preincubated at 37 degrees C for 10 min,
      reactions were started by the addition of ATP, and plates were incubated for an
      additional 60 min at 37 degrees C. Reactions were stopped by sodium dodecyl
      sulfate (SDS). Inorganic phosphate (P(i)) was measured by modifications of the
      method by Fiske and Subbarow, (Fiske and Subbarow, 1925) in the same plate using
      a plate reader. The P(i) assay range was between 0 and 250 nm/mL. Results
      obtained for intraassay precision, (n = 7) are as follows: Mg2+ ATPase = 4.39 +/-
      0.25 (5.7% CV); Na+/K(+)-ATPase = 7.33 +/- 0.40 (5.4% CV); Ca2+ ATPase = 15.86 +/
      0.76 (4.8% CV); and CaM-activated Ca2+ ATPase = 74.12 +/- 2.34 (3.2% CV) (nmole
      P(i)/mg protein/min.). This is a rapid, simple, and nonisotopic method for the
      determination of membrane-bound ATPases activities. All steps are performed in
      the same microtiter plate, thus reducing handling and associated errors.

PMID- 8298182
TI  - Free radicals and the heart.
AB  - Because of the molecular configuration, most free radicals are highly reactive
      and can cause cell injury. Protective mechanisms have evolved to provide defense
      against free-radical injury. Any time these defense systems are overwhelmed, such
      as during disease states, cell dysfunction may occur. In this review we discuss
      cellular sources as well as the significance of free radicals, oxidative stress,
      and antioxidants. A probable role of oxidative stress in various cardiac
      pathologies has been also analyzed. Although some methods for the detection of
      free radicals as well as oxidative stress have been cited, better methods to
      study the quantity as well as subcellular distribution of free radicals are
      needed in order to understand fully the role of free radicals in both health and
      disease.

PMID- 8298183
TI  - A method to screen for the antioxidant effect of compounds on low-density
      lipoprotein (LDL): illustration with flavonoids.
AB  - We used a recently described anion-exchange chromatographic method (Vedie et al.
      J Lipid Res 1991;32:1359) to study the protective effect of potential inhibitors
      of low-density lipoprotein (LDL) oxidation mediated by cupric ion. By way of an
      example, we studied eight flavonoids (flavone, 3-hydroxyflavone, chrysin,
      galangin, fisetin, morin, quercetin, and myricetin) as well as three non
      flavonoid antioxidants, butylated hydroxytoluene (BHT), probucol, and vitamin C,
      as reference compounds. Each compound was tested at various concentrations (1-100
      microM). For flavonoid concentrations of 10 microM, an index was calculated as
      the (LDL control-flavonoid)/(LDL control-probucol) ratio, in which each term is
      expressed as the percentage of the most electronegative LDL fraction (fraction
      E). If the index is positive, the flavonoid inhibits LDL oxidation. A value > 1
      (3-hydroxyflavone and galangin) means greater activity than probucol, whereas a
      value < 1 means lower activity (fisetin). If the index is around 0 (flavone and
      chrysin), the flavonoid is inactive. Finally, a negative value reflects possible
      prooxidant activity (morin, quercetin, and myricetin). Our results show that this
      chromatographic method can be applied to screening new pharmacological agents for
      activity against LDL oxidation.

PMID- 8298184
TI  - The isolated perfused bovine udder as an in vitro model of percutaneous drug
      absorption. Skin viability and percutaneous absorption of dexamethasone, benzoyl
      peroxide, and etofenamate.
AB  - Using udders from slaughtered cows as a new in vitro model of percutaneous drug
      absorption, the tissue viability and the percutaneous absorption of
      dexamethasone, benzoyl peroxide, and etofenamate were studied. The organ was
      perfused with gassed tyrode solution for up to 6 hr. As shown by measurement of
      glucose consumption, lactate production, lactate dehydrogenase activity, and pH
      in the perfusate, the tissue was viable over a 6-hr period. This was confirmed by
      a histological examination. Determination of the udder skin-fold thickness
      demonstrated that no edema developed within the perfusion period. A maximum skin
      penetration of dexamethasone was found after administration of dexamethasone
      dissolved in acetone with dimethyl sulfoxide, followed by ointment with salicylic
      acid, ointment without salicylic acid, and acetone solution. Experiments with
      benzoyl peroxide and etofenamate demonstrated that the perfused udder skin was
      capable of metabolizing drugs in vitro. In conclusion, the isolated perfused
      bovine udder is a new in vitro model, which maintains bovine udder skin with an
      isolated vasculature in a viable state. Using this in vitro model, we note it is
      possible to compare the dermal penetration, metabolism, and absorption of
      substances after topical administration of different drug formulations.

PMID- 8298185
TI  - Physical dependence on morphine induced in dogs via the use of miniosmotic pumps.
AB  - The difference between the development of physical dependence on morphine
      administered via Alzet miniosmotic pumps as well as syringe injection (twice a
      day) at fixed times was examined in conscious dogs. Physical dependence was
      quantified by polygraphically measuring naloxone-precipitated withdrawal signs on
      the day 8 after the subcutaneous implantation of miniosmotic pumps which supplied
      morphine at 1-5 mg/kg/day. Morphine plasma levels were maintained at 19-25 and 41
      47 ng/mL during infusions of morphine at doses of 2.5 and 5 mg/kg/day,
      respectively. Morphine withdrawal was characterized by hyperactivity, biting,
      digging, tremors, nausea, hyperthermia, and increased wakefulness, and by
      electroencephalographic (EEG) activation in the amygdala and hippocampus,
      followed by dissociation of the EEG in the cortex (fast wave) from that in the
      limbic (slow wave) system, increased heart rates, and raised blood pressure.
      These morphine withdrawal signs seemed to be more severe than those exhibited in
      animals that had received syringe injections of morphine at the same doses. These
      results suggest that the use of miniosmotic pumps in dogs may be a very
      convenient and useful method for both evaluating drug dependence and studying its
      mechanisms.

PMID- 8298186
TI  - Methods for implanting steroid-containing cannulae into the paraventricular
      nucleus of neonatal rats.
AB  - Implantation of cannulae into brains of neonatal rats presents methodological
      difficulties. We discuss such issues as avoiding tissue injury, and describe
      successful techniques. Cannulae size, methods of preparation, insertion, and
      securing are evaluated. We present a modified cannula holder applicable to the
      soft neonatal brain. Application of these methods to the study of glucocorticoid
      receptors in the neonatal rat hypothalamus is illustrated.

PMID- 8298187
TI  - Fission yeast genes nda1+ and nda4+, mutations of which lead to S-phase block,
      chromatin alteration and Ca2+ suppression, are members of the CDC46/MCM2 family.
AB  - Fission yeast cold-sensitive mutants nda1-376 and nda4-108 display a cell cycle
      block phenotype at the restrictive temperature (cell elongation with the single
      nucleus) accompanied by an alteration in the nuclear chromatin region. DNA
      content analysis shows that the onset of DNA synthesis is blocked or greatly
      delayed in both mutant cells, the block being reversible in nda4-108. Upon
      release to the permissive temperature, nda4-108 cells resumed replicating DNA,
      followed by mitosis and cytokinesis. The nda4 phenotype was partly rescued by the
      addition of Ca2+ to the medium; Ca2+ plays a positive role in the nda4+ function.
      The predicted protein sequences of nda1+ and nda4+ isolated by complementation
      are similar to each other and also, respectively, to those of the budding yeast,
      MCM2 and CDC46, both of which are members of the gene family required for the
      initiation of DNA replication. The central domains of these proteins are
      conserved, whereas the NH2- and COOH- domains are distinct. Results of the
      disruption of the nda1+ and nda4+ genes demonstrates that they are essential for
      viability.

PMID- 8298188
TI  - Suppression of yeast geranylgeranyl transferase I defect by alternative
      prenylation of two target GTPases, Rho1p and Cdc42p.
AB  - Geranylgeranyl transferase I (GGTase I), which modifies proteins containing the
      sequence Cys-Ali-Ali-Leu (Ali: aliphatic) at their C-termini, is indispensable
      for growth in the budding yeast Saccharomyces cerevisiae. We report here that
      GGTase I is no longer essential when Rho1p and Cdc42p are simultaneously
      overproduced. The lethality of a GGTase I deletion is most efficiently suppressed
      by provision of both Rho1p and Cdc42p with altered C-terminal sequences (Cys-Ali
      Ali-Met) corresponding to the C-termini of substrates of farnesyl transferase
      (FTase). Under these circumstances, the FTase, normally not essential for growth
      of yeast, becomes essential.

PMID- 8298189
TI  - Induction of starfish oocyte maturation by the beta gamma subunit of starfish G
      protein and possible existence of the subsequent effector in cytoplasm.
AB  - beta gamma subunits of G proteins were purified from starfish oocytes, and their
      role in the induction of oocyte maturation by 1-methyladenine was investigated.
      When injected into starfish oocytes, the purified beta gamma subunit of the
      starfish G protein induced germinal vesicle breakdown (GVBD) faster than that of
      bovine brain G protein. Injection of the starfish beta gamma into cytoplasm near
      the germinal vesicle (GV) induced GVBD earlier than when injected into the GV or
      the cytoplasm near the plasma membrane. Fluorescent-labeled beta gamma was
      retained in the injected area even after GVBD. Injected beta gamma also induced
      the formation of maturation-promoting factor as well as an increase of histone H1
      kinase activity. These results suggest that beta gamma dissociates from alpha
      subunit by the stimulation of 1-methyladenine and interacts with a cytoplasmic
      effector, which results in formation of active cdc2 kinase.

PMID- 8298190
TI  - How the transition frequencies of microtubule dynamic instability (nucleation,
      catastrophe, and rescue) regulate microtubule dynamics in interphase and mitosis:
      analysis using a Monte Carlo computer simulation.
AB  - Microtubules (MTs) in newt mitotic spindles grow faster than MTs in the
      interphase cytoplasmic microtubule complex (CMTC), yet spindle MTs do not have
      the long lengths or lifetimes of the CMTC microtubules. Because MTs undergo
      dynamic instability, it is likely that changes in the durations of growth or
      shortening are responsible for this anomaly. We have used a Monte Carlo computer
      simulation to examine how changes in the number of MTs and changes in the
      catastrophe and rescue frequencies of dynamic instability may be responsible for
      the cell cycle dependent changes in MT characteristics. We used the computer
      simulations to model interphase-like or mitotic-like MT populations on the basis
      of the dynamic instability parameters available from newt lung epithelial cells
      in vivo. We started with parameters that produced MT populations similar to the
      interphase newt lung cell CMTC. In the simulation, increasing the number of MTs
      and either increasing the frequency of catastrophe or decreasing the frequency of
      rescue reproduced the changes in MT dynamics measured in vivo between interphase
      and mitosis.

PMID- 8298191
TI  - Segregated assembly of muscle myosin expressed in nonmuscle cells.
AB  - Skeletal muscle myosin cDNAs were expressed in a simian kidney cell line (COS)
      and a mouse myogenic cell line to investigate the mechanisms controlling early
      stages of myosin filament assembly. An embryonic chicken muscle myosin heavy
      chain (MHC) cDNA was linked to constitutive promoters from adenovirus or SV40 and
      transiently expressed in COS cells. These cells accumulate hybrid myosin
      molecules composed of muscle MHCs and endogenous, nonmuscle, myosin light chains.
      The muscle myosin is found associated with a Triton insoluble fraction from
      extracts of the COS cells by immunoprecipitation and is detected in 2.4 +/- 0.8
      micron-long filamentous structures distributed throughout the cytoplasm by
      immunofluorescence microscopy. These structures are shown by immunoelectron
      microscopy to correspond to loosely organized bundles of 12-16-nm-diameter myosin
      filaments. The muscle and nonmuscle MHCs are segregated in the transfected cells;
      the endogenous nonmuscle myosin displays a normal distribution pattern along
      stress fibers and does not colocalize with the muscle myosin filament bundles. A
      similar assembly pattern and distribution are observed for expression of the
      muscle MHC in a myogenic cell line. The myosin assembles into filament bundles,
      1.5 +/- 0.6 micron in length, that are distributed throughout the cytoplasm of
      the undifferentiated myoblasts and segregated from the endogenous nonmuscle
      myosin. In both cell lines, formation of the myosin filament bundles is dependent
      on the accumulation of the protein. In contrast to these results, the expression
      of a truncated MHC that lacks much of the rod domain produces an assembly
      deficient molecule. The truncated MHC is diffusely distributed throughout the
      cytoplasm and not associated with cellular stress fibers. These results establish
      that the information necessary for the segregation of myosin isotypes into
      distinct cellular structures is contained within the primary structure of the MHC
      and that other factors are not required to establish this distribution.

PMID- 8298192
TI  - Function of the ypt2 gene in the exocytic pathway of Schizosaccharomyces pombe.
AB  - The ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of
      the ypt/rab family of small GTP-binding proteins, related in sequence to Sec4p of
      Saccharomyces cerevisiae but closer to mammalian rab8. We have introduced a
      mutation into the gene corresponding to a mutation identified in ypt1, in which a
      conserved valine residue was altered to asparagine. The mutated ypt2 gene was
      introduced into the S. pombe genome by gene replacement. The resulting strain was
      temperature-sensitive for growth. Normal growth was restored by introduction of a
      plasmid-borne wild-type ypt2 cDNA or by cDNA for rab8 but not by various other
      rab or ypt sequences. At restrictive temperature the mutant cells accumulated the
      secretory protein acid phosphatase in a form that appeared to be fully
      glycosylated and acquired a population of vesicles detectable by electron
      microscopy. Thus the ypt2 protein, and by inference rab8, appear to function in
      the last stage of the secretory pathway.

PMID- 8298193
TI  - Regulated expression of the human beta globin gene in transgenic mice requires an
      upstream globin or nonglobin promoter.
AB  - Transgenic mice have been used extensively to study elements governing the
      erythroid-specific developmental switch from human fetal gamma to human adult
      beta globin. Previous work demonstrated that a small construct composed of
      hypersensitive site 2 (HS2) of the locus control region (LCR) linked to the gamma
      and beta globin genes (HS2-gamma-beta) is sufficient for correct tissue and
      temporal expression of these genes, whereas HS2-beta alone is inappropriately
      expressed in the embryo. Two models, which are not mutually exclusive, have been
      proposed to explain these results and those of other constructs in transgenic
      mice. One model emphasizes the conserved polarity in the globin locus and
      suggests a distance effect whereby the beta globin gene must be removed from the
      LCR/HS2 to prevent an early and incorrect activation of this gene in the
      embryonic compartment. A second hypothesis proposes a competition between the
      gamma and beta globin gene promoters for interaction with the LCR/HS2. The active
      gamma globin gene promoter positioned between the LCR/HS2 and the beta globin
      gene thereby interacts with the HS2 elements early in erythroid development and
      is expressed until a change in putative stage-specific nuclear factors makes an
      interaction with the adult beta globin gene more favorable. In an effort to test
      the competition model, a construct has been prepared in which a small deletion
      was produced in the promoter region of the gamma globin gene while in the context
      of the HS2-gamma-beta plasmid. Analysis of this construct in transgenic mice
      reveals a constitutive unregulated expression of the human beta globin gene
      during erythroid development. To determine if this competition effect is specific
      for globin genes, a heterologous reporter gene has been substituted for the gamma
      globin gene in the construct HS2-gamma-beta. In this case, the beta globin gene
      exhibits correct developmental expression. This data is consistent with a model
      in which transcription from a promoter upstream of the beta globin gene in some
      manner protects this adult gene from activation by the LCR/HS2 during early
      development.

PMID- 8298194
TI  - Basic fibroblast growth factor modulates integrin expression in microvascular
      endothelial cells.
AB  - During angiogenesis capillary endothelial cells undergo a coordinated set of
      modifications in their interactions with extracellular matrix components. In this
      study we have investigated the effect of the prototypical angiogenic factor basic
      fibroblast growth factor (bFGF) on the expression and function of several
      integrins in microvascular endothelial cells. Immunoprecipitation experiments
      with antibodies to individual subunits indicated that microvascular cells express
      at their surface several integrins. These include the alpha 1 beta 1, alpha 2
      beta 1, and alpha 3 beta 1 laminin/collagen receptors; the alpha 6 beta 1 laminin
      receptor; the alpha 5 beta 1 and alpha v beta 1 fibronectin receptors; the alpha
      6 beta 4 basement membrane receptor; and the alpha v beta 3 and alpha v beta 5
      vitronectin receptors. Treatment with bFGF caused a significant increase in the
      surface expression of the alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha 6
      beta 1, alpha 6 beta 4, and alpha v beta 5 integrins. In contrast, the level of
      expression of the alpha 1 beta 1 and alpha v beta 3 integrins was decreased in
      bFGF-treated cells. Immunoprecipitation of metabolically labeled cells indicated
      that bFGF increases the biosynthesis of the alpha 3, alpha 5, alpha 6, beta 4,
      and beta 5 subunits and decreases the production of the alpha v and beta 3
      subunits. These results suggest that bFGF modulates integrin expression by
      altering the biosynthesis of individual alpha or beta subunits. In accordance
      with the upregulation of several integrins observed in bFGF-treated cells, these
      cells adhered better to fibronectin, laminin, vitronectin, and type I collagen
      than did untreated cells. The largest differences in beta 1 integrin expression
      occurred approximately 72 h after exposure to bFGF, at a time when the expression
      of the endothelial cell-to-cell adhesion molecule endoCAM was also significantly
      upregulated. In contrast, a shorter exposure to bFGF (24-48 h) was required for
      the maximal induction of plasminogen activator production in the same cells.
      Taken together, these results show that bFGF causes significant changes in the
      level of expression and function of several integrins in microvascular
      endothelial cells.

PMID- 8298195
TI  - Differential regulation of early response genes and cell proliferation through
      the human granulocyte macrophage colony-stimulating factor receptor: selective
      activation of the c-fos promoter by genistein.
AB  - Granulocyte macrophage colony-stimulating factor (GM-CSF) binds to the high
      affinity GM-CSF receptor (GMR) consisting of alpha and beta subunits and induces
      rapid tyrosine phosphorylation, activation of early response genes, and
      proliferation of hematopoietic cells. The alpha subunit is the primary cytokine
      binding component and the beta subunit is required for high-affinity binding as
      well as for signal transduction. Using tyrosine kinase inhibitors and cytoplasmic
      deletion mutants of the beta subunit, we obtained evidence that there are at
      least two distinct pathways downstream of the GMR in BA/F3 cell, one which is
      essential for proliferation, leads to the c-myc gene activation, and is sensitive
      to herbimycin and genistein. Activation of this pathway depends on the
      cytoplasmic region between amino acid positions 455 and 517 of the beta subunit.
      The second pathway, which leads to activation of c-fos and c-jun genes, is only
      partially sensitive to herbimycin, is resistant to genistein and depends on the
      region between amino acid positions 626 and 763 of the beta subunit.
      Unexpectedly, the c-fos mRNA induction was augmented by genistein. The enhanced
      expression of c-fos mRNA by genistein also occurred with stimulation with cAMP,
      PMA, or EGF in NIH3T3 cells. It thus seems likely that genistein affects a common
      pathway downstream of these signals.

PMID- 8298197
TI  - Clinical pharmacology of alendronate sodium.
AB  - Clinical studies have been performed to investigate the pharmacokinetics and
      pharmacodynamics of alendronate, an inhibitor of bone resorption for the
      treatment of osteoporosis. Alendronate is one of the most potent bisphosphonates
      currently undergoing clinical investigation (> 100-fold more potent than
      etidronate in vivo). The pharmacokinetics of alendronate are similar to those of
      other bisphosphonates. After a 2-h intravenous infusion, plasma concentrations of
      alendronate decline rapidly to approximately 5% of initial values within 6 h.
      About 50% of a systemic dose is excreted unchanged in the urine in the 72 h
      following administration. By analogy to its behavior in animals the remainder is
      assumed to be taken up by the skeleton. After sequestration into bone, the
      elimination of alendronate is very prolonged. The terminal half-life was
      estimated to be greater than 10 years. Despite prolonged skeletal residence, the
      biological effects of alendronate begin to diminish post-treatment, since the
      duration of effect reflects factors besides dose and cumulative drug exposure.
      When taken after an overnight fast, 2 h before breakfast, the oral
      bioavailability of alendronate averages approximately 0.75% of dose with
      substantial variability (coefficient of variation 55%-75%) both between and
      within subjects. Reducing the wait before food from 2 h to 1 h, or even 30 min,
      produces a mean reduction in absorption of 40%. Since the clinical efficacy of
      alendronate is indistinguishable whether it is given 30 min, 1h, or 3 h before a
      meal, the observed variability in bioavailability within this range is of little
      consequence. Dosing up to at least 2 h after a meal dramatically reduces
      absorption (80%-90%).

PMID- 8298198
TI  - Short-term effect of alendronate on bone mass and bone remodeling in
      postmenopausal women.
AB  - The short-term dose-response relationship between treatment with the
      bisphosphonate alendronate, biochemical markers of bone turnover, and changes in
      lumbar spine bone mineral density (BMD) over 9 months was assessed using a double
      masked controlled study design in 65 postmenopausal women (mean age 51.6 years,
      mean 1.5 years since last menses) receiving 5, 20, 40 mg of alendronate or
      placebo for 6 weeks. After 6 weeks of alendronate, serum calcium phosphate and
      osteocalcin decreased, and intact parathyroid hormone increased significantly in
      dose-dependent fashions in the alendronate-treated groups (T) compared with
      placebo (P). Generally similar changes (decreases) were noted in 24-h urinary
      calcium and pyridinoline (deoxy- and hydroxylysl pyridoline); by 30 weeks post
      treatment no significant changes from baseline or between T and P were noted.
      Lumbar BMD by dual-energy X-ray absorptiometry demonstrated a dose-dependent
      response over 9 months (median % change +/- SD: -1.2 +/- 0.9 for 5 mg T, +0.7 +/-
      0.8 for 20 mg T*, +1.2 +/- 1.1 for 40 mg T*;*p < 0.01 vs P). Alendronate was
      generally well tolerated over all dosages. These data demonstrate that short-term
      (6 weeks) oral alendronate treatment (5-40 mg daily) is well tolerated and
      effective in (reversibly) decreasing biochemical markers of bone turnover in
      early postmenopausal women, and in stabilizing spinal BMD over 9 months. Longer
      term treatment with larger clinical populations is indicated to define more fully
      the potential efficacy and safety of chronic alendronate therapy.

PMID- 8298196
TI  - Movement of the free catalytic subunit of cAMP-dependent protein kinase into and
      out of the nucleus can be explained by diffusion.
AB  - The catalytic (C) subunit of cyclic AMP (cAMP) dependent protein kinase (PKA) has
      previously been shown to enter and exit the nucleus of cells when intracellular
      cAMP is raised and lowered, respectively. To determine the mechanism of nuclear
      translocation, fluorescently labeled C subunit was injected into living REF52
      fibroblasts either as free C subunit or in the form of holoenzyme (PKA) in which
      the catalytic and regulatory subunits were labeled with fluorescein and
      rhodamine, respectively. Quantification of nuclear and cytoplasmic fluorescence
      intensities revealed that free C subunit nuclear accumulation was most similar to
      that of macromolecules that diffuse into the nucleus. A glutathione S-transferase
      C subunit fusion protein did not enter the nucleus following cytoplasmic
      microinjection. Puncturing the nuclear membrane did not decrease the nuclear
      concentration of C subunit, and C subunit entry into the nucleus did not appear
      to be saturable. Cooling or depleting cells of energy failed to block movement of
      C subunit into the nucleus. Photobleaching experiments showed that even after
      reaching equilibrium at high [cAMP], individual molecules of C subunit continued
      to leave the nucleus at approximately the same rate that they had originally
      entered. These results indicate that diffusion is sufficient to explain most
      aspects of C subunit subcellular localization.

PMID- 8298199
TI  - Treatment of postmenopausal osteoporosis with continuous daily oral alendronate
      in comparison with either placebo or intranasal salmon calcitonin.
AB  - Alendronate sodium (ALN) is a potent amino bisphosphonate which specifically
      inhibits osteoclastic bone resorption and has been found to reverse bone loss in
      several animal models. To determine if daily oral ALN treatment could prevent or
      reverse bone loss in osteoporotic postmenopausal women, and to compare ALN to
      intranasal salmon calcitonin (CT), a 2-year, double-masked, randomized, placebo
      controlled study was initiated at 9 clinical centers in Italy. Two hundred and
      eighty six postmenopausal women (age 48-76) with spinal bone mineral density
      (BMD) > or = 2 SD below adult mean peak, with or without vertebral crush
      fractures, were randomized to one of four treatment arms: ALN 10 mg daily, ALN 20
      mg daily or matching placebo (these groups all double-masked), or CT 100 IU daily
      (open label) for 2 years. All patients received supplemental calcium (as
      carbonate) 500 mg daily. Bone mass was measured by dual-energy X-ray
      absorptiometry of the PA lumbar spine (LS) and proximal femur (femoral neck and
      trochanter) at 6-month intervals. Subject safety was measured through sequential
      clinical and laboratory evaluation. A planned 1-year interim analysis of this
      ongoing study was performed centrally in a manner that maintains the double-mask
      for all subjects receiving oral study drug. Relative to PBO, ALN at either 10 mg
      or 20 mg daily increased LS BMD by 4.7% and 6.1%, respectively; each increased
      femoral neck BMD by 3.1% and increased trochanter BMD by 3.3% and 3.8%
      respectively. In contrast, CT failed to significantly increase BMD of either the
      spine, femoral neck or trochanter, either relative to baseline or to
      PBO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298201
TI  - Bisphosphonates in osteoporosis: an introduction.
AB  - The bisphosphonates are compounds characterized by a P-C-P bond. By substitution
      of the hydrogens on the carbon atom it is possible to synthesize a variety of
      bisphosphonates each with its own distinct physicochemical, pharmacological, and
      toxicological characteristics. The bisphosphonates investigated for use in bone
      disease have, in general the following properties: they bind strongly onto bone
      mineral, inhibit calcium phosphate crystal formation and dissolution, inhibit
      normal and ectopic mineralization (probably through a physicochemical inhibition
      of crystal growth), and inhibit bone resorption. The last effect is cell
      mediated, the exact mechanism being unknown, and is exquisitely dependent upon
      bisphosphonates used. Various bisphosphonates have been investigated extensively
      in animals for a possible use in osteoporosis. They were found not only to
      increase the balance of calcium in normal rats but also to prevent various types
      of experimental osteoporosis, such as occurs after immobilization, ovariectomy,
      or administration of corticosteroids. the toxicity of these compounds is
      relatively low, probably because they are cleared rapidly from the plasma to be
      deposited preferentially in the bone, where they remain over a long time. In man,
      bisphosphonates are used successfully in diseases with increased bone turnover,
      such as Paget's disease and tumoral bone disease. Recently, a few have been
      investigated in osteoporosis. They were shown not only to inhibit bone loss but
      also to increase bone mass. The effect on the rate of fractures is not yet
      proven, but the first results look promising. Many issues as yet unsolved, will
      be essential for the choice of the best compound in osteoporosis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8298200
TI  - Design of the Fracture Intervention Trial.
AB  - The Fracture Intervention Trial (FIT) is a randomized, double-masked, placebo
      controlled trial designed to test the hypothesis that alendronate, an amino
      bisphosphonate, will reduce the rate of fractures in women aged 55-80 years with
      low hip bone marrow density (< 0.68 gm/cm2 at the femoral neck). It is being
      conducted at 11 clinical centers around the United States with a coordinating
      center at UC San Francisco. The goal was to randomize 6000 women. When
      recruitment was completed (in May 1993), 6457 women had been randomized,
      amounting to 108% of goal. The women were assigned to one of two substudies. The
      first (Vertebral Deformity study) includes 2023 women who have at least one
      vertebral deformity, and will test the hypothesis that alendronate reduces the
      rate of new vertebral deformities during 3 years of follow-up. This substudy has
      a power of 0.90 to detect a 32% reduction in the incidence of new vertebral
      deformities, assuming a 6.5% annual incidence of new vertebral deformities in the
      placebo group. The second study (Clinical Fracture study) includes 4434 women
      without vertebral deformities at baseline and will test the hypothesis that
      alendronate reduces the rate of clinically recognized fractures of all types over
      an average of 4.25 years of follow-up. This substudy has a 0.90 power to detect a
      25% reduction in the rate of all clinical fractures, assuming 4% annual incidence
      in the placebo group. To our knowledge, this is the largest prospective,
      randomized, controlled study undertaken to determine the effectiveness of a
      treatment in reducing the risk of fractures in postmenopausal women.

PMID- 8298202
TI  - Alendronate: some remaining paradoxes.

PMID- 8298203
TI  - Preclinical pharmacology of alendronate.
AB  - This brief review summarizes some of the preclinical findings of studies aimed at
      assessing the efficacy and safety of the aminobisphosphonate alendronate (ALN) in
      preventing or restoring the bone loss caused by calcium or estrogen deficiency.
      Mode of action studies show that ALN localizes at sites of bone resorption and
      inhibits osteoclastic activity. In secondary hyperparathyroidism caused by
      calcium-deficient diets in the rat, ALN reduced the bone loss. For low doses,
      daily administration proved most efficient. In ovariectomized rats, ALN both
      prevented and reversed the bone changes produced by estrogen deficiency at oral
      doses equivalent to 0.1 mg/kg per day or higher, and also maintained the
      mechanical strength of vertebrae. In ovariectomized baboons, which show bone
      changes similar to those seen in ovariectomized women, ALN also prevented the
      increase in bone turnover and increased both bone volume and bone strength in
      vertebrae. In a comparative study between ALN and etidronate, we found that ALN
      was 1000-fold more potent in inhibiting bone resorption and had at least a 1000
      fold higher safety margin with respect to inhibition of mineralization and
      osteomalacia.

PMID- 8298204
TI  - [Requirements for graduates of training courses from the viewpoint of various
      specialty fields].
AB  - Against the background of rehabilitation as practised within the legal German
      framework of statutory and compulsory old age pension insurance--this
      rehabilitation scheme having developed continually, getting more and more
      differentiated for the last 40 years--we welcome the post-graduates of the
      specialised training curriculae in Public Health. The post-graduates are expected
      not only to acquire differentiated knowledge of the various spheres of activities
      of the different statutory social insurance and welfare bodies, but also to
      possess so to say a "sixth sense" regarding the "quality" of the individual
      spheres. Governed by the concepts of economy of means, triftiness and efficiency
      it is always imperative to ensure that the best possible care is offered to an
      individual in need and to plan further developments. The postgraduate must
      therefore be capable of becoming integrated within a team and to appreciate the
      expectations of members of other professions in order to eventually participate
      in creating feasible solutions within the framework of the hierarchically
      preferential demands inherent in the various spheres.

PMID- 8298205
TI  - [Requirements of graduates of training courses from the viewpoint of research
      done outside of universities].
AB  - In the near future the emphasis of research and consulting institutes outside
      university will lie in the rationalization within the health care system as well
      as in the determination of criteria for the rationing of the health services.
      Therefore it is essential that post-graduates acquire the ability to integrate
      knowledge of economics and management into the analysis and evaluation of the
      efficiency of medical service.

PMID- 8298206
TI  - [Promoting competence in a model trial of a complementary course of study in
      health sciences/public health at the Berlin Technical University in cooperation
      with the Free University and other science and general practice institutions].
AB  - Since October 1992 (winter semester 92/93) graduates are being educated in Public
      Health at Berlin Technical University in cooperation with the Free University of
      Berlin as well as with the Humboldt University of Berlin and other institutions
      of science and practice in Berlin and Brandenburg. For the time being the course
      of studies is a pilot project for 4 years. The aim of the postgraduate studies is
      the creation of permanent structures and therefore institutionalisation. It is
      open to graduates and college graduates of public-health relevant subject areas
      of specialisation are "Health Promotion in the community and at the workplace"
      and "Planning and Management in Health Services". The course of studies takes 4
      semesters and is divided into basic studies, studies of main points of emphasis
      and project studies. Social medicine and especially epidemiology are part of the
      basic disciplines, which are indispensable for finding the way of looking at
      problems concerning public health. The reason for the peculiarity with regard to
      establishing public health at other German universities are the main topics
      representing the interaction between the technical and ecological development of
      health. The graduate degree is "Magister of Public Health". During the time of
      the pilot project the course of studies is subjected to external and internal
      surveillance regarding quality assurance and quality optimisation of teaching and
      organisation of the studies. On the one hand this is done by an external advisory
      committee and on the other hand by internal and external evaluation.

PMID- 8298207
TI  - [Promoting competence in training courses--"health sciences--public health" at
      the Dresden Medical Academy].
AB  - The postgraduate study "Gesundheitswissenschaften--Public Health" of the Medical
      Academy of Dresden was started at 1991. Reasons are given for the necessity of
      Public-Health education in the new Laender of the FRG. Basing on the previous
      experiences some examples are given for the development of public-health
      competence for students, teachers and a Medical Faculty. Some difficulties in the
      job market are discussed.

PMID- 8298208
TI  - [Promoting competence in training courses in Germany--complementary education in
      health sciences and social medicine and the Dusseldorf University].
AB  - The article summarises the aims, organisational background and essential contents
      of the postgraduate training programme offered by the Medical Faculty of the
      University in cooperation with the Academy of Public Health at Dusseldorf. The
      five topical areas which define the essence of the two years curriculum are
      described. On the basic of this knowledge, participants are expected to
      successfully solve theoretical, methodological and practical problems in
      different areas of medically oriented public health activities.

PMID- 8298209
TI  - [Promoting competence in training courses--complementary curriculum in
      "population medicine and health sciences--public health" at the Hannover Medical
      University].
AB  - Public Health professionals should have various knowledge and abilities. The
      Public Health programme at Hannover Medical School offers a training with well
      defined practice related elements. It includes also special courses of social
      medicine for both groups together, the medical students as well as the
      postgraduate public health students.

PMID- 8298210
TI  - [International solutions for promoting social medicine competence in training
      courses--the London School of Hygiene and Tropical Medicine].
AB  - The London School of Hygiene & Tropical Medicine is an important institution for
      postgraduate teaching and research in public health and tropical medicine.
      Advanced training is provided in a wide range of disciplines leading to different
      qualifications. As an example the Master of Science course in Public Health
      Medicine is used: Training is provided by a one-year course divided in three
      terms. The first term starts with an orientation period and shared-core
      components. In the second term teaching is largely based on study units. Term
      three is mainly project work. A training course for membership examination of the
      Faculty of Public Health Medicine is also offered.

PMID- 8298211
TI  - [1st expert's exchange at the seminar series "Discussions on Public Health".
      Competence in social medicine--basic for medical studies, fundamental in graduate
      training courses. Reports from the meeting, 4-5 February 1992, Witten/Herdecke].

PMID- 8298212
TI  - [Needs for social medicine competence and developing social medicine competence-
      essentials for expert consultation].

PMID- 8298213
TI  - [Providing educational goals in social medicine for the practicing physician in
      basic medical education].
AB  - Social Medicine has a long and successful tradition in providing public medical
      care, but it does not have a long-standing academic tradition. To this very date,
      some medical faculties have neither a representative of the discipline nor a
      corresponding institute. Although the topics of Social Medicine are manifold,
      there is a discrepancy in the time allotted for teaching within the medical
      curriculum. Social Medicine must offer practical and orientational knowledge. In
      the medical faculties, Social Medicine also represents the health sciences, and
      in the Schools of Public Health it has the function of a bridge discipline and is
      the most prominent representative of medicine.

PMID- 8298214
TI  - [Prevalent disease characteristics in the ambulatory sector--need for social
      medicine competence with reference to hard-to-define and undefined disease
      pictures].
AB  - Poorly defined or undefined disease patterns occur sporadically in the
      physician's daily routine. They appear as uncharacteristic, early and compensated
      stages of disease. Sociomedical competence can contribute to cope with illness,
      where physician and patient are unable to cope on the basis of diagnostic and
      clinical categories alone. It allows to understand the individual concept of
      illness as a construct, answering several purposes and dependent on the acting
      individuals and on the particular situation. The search for better solutions
      within the system opens many ways to redefine, reframe, behavioural change and
      structures beyond the limits of a clinical concept of disease. This requires
      theoretical knowledge about the complex effects an intervention may have. In
      medical training it is necessary to emphasise problem-orientated learning
      strategies to promote systemic understanding of the context of health and disease
      in the perspective of the individual and also from a social point of view.

PMID- 8298215
TI  - [Need for social medicine competence of ambulatory care physicians in the
      treatment and management of diseases].
AB  - There is a great demand for sociomedical competence of general practitioners who
      as "family doctors" must be consulted by the patient first before consulting a
      specialist (so-called "primararztliche Versorgung" according to German compulsory
      statutory sickness insurance legislation). Special and continuing education of
      general practitioners is sadly neglected within the legislative framework
      governing medical studies and training. The biopsychic care concept can be
      translated into reality only by means of high-level sociomedical competence.
      Increase in competence seems possible only if medical sociology is liberated from
      its preclinical isolation.

PMID- 8298216
TI  - [Expectations of self-help groups of the social medicine competence of physicians
      -a contribution from the viewpoint of social work in the course and management of
      chronic diseases exemplified by multiple sclerosis].
AB  - Doctors dealing with incurable chronic ill patients need to show empathy and
      should be capable of assessing social and occupational consequences of diseases.
      They should also know about potential rehabilitative measures as well as
      entitlements or connect patients with respective resource persons. Self help
      groups can be very conducive to coping with a disease. However, physicians still
      know too little about them or consider them competitors.

PMID- 8298217
TI  - [Goals in social medicine education for the practicing physician from the
      viewpoint of social security pensions].
AB  - The tasks of a medical doctor employed by annuity insurance institutions, e.g.
      those of the Federal State, are complex. The doctors work in administration, in
      medical expert offices, and rehabilitation centres. Their tasks thus comprise the
      compilation of expert reports, consultation services for the administration, and
      modern rehabilitation diagnostics and therapy in specialised hospitals. In this
      context, thorough knowledge and understanding of general medicine as well as an
      open mind for comprehensive concepts are required. Education and training in
      social medicine or community health care are still far from perfect, and
      community medicine is not sufficiently developed as part of medical studies.
      Consequently, these areas must be strengthened. Annuity insurance institutions
      cooperate with academies for social medicine in order to improve postgraduate
      training in social medicine.

PMID- 8298218
TI  - [Developing social medicine competence in medical education--goals in social
      medicine education for the practicing physician from the viewpoint of mandatory
      public insurance].
AB  - The social obligation of medicine is not limited to the application of technical
      curative methods. It rather also encompasses prevention, rehabilitation as well
      as cooperation with other health professions. Furthermore, medicine is tied into
      a social, economical and legal framework which has a direct impact on medical
      practice. Training in social medicine within the medical curriculum has to
      address these relationships. Moreover, the interaction between the ecological,
      occupational and social environment and the causes of diseases and disabilities
      should be a central focus of the subject.

PMID- 8298219
TI  - [Goals in social medicine education for the practicing physician from the
      viewpoint of the medical profession].
AB  - The acquisition of socio-medical knowledge must increasingly be taken into
      account: the future doctor must be enabled to recognise the "polyvalency" of
      sociomedical problems and perspectives. Relevant impulses of the German medical
      profession are outlined.

PMID- 8298220
TI  - [Goals of the licensing regulation in social medicine education].
AB  - The importance of social medicine is generally recognised, but deficits still
      exist, not because of any lack of legal provisions in German legislation
      governing the permission of doctors to practise medicine, but because the
      discipline of social medicine is understaffed at universities on the one hand,
      whereas infrastructures are insufficient and training is not properly coordinated
      and closely meshed on the other. A paradigmatic change is imperative. A first
      step in the right direction is the increase in postgraduate training courses. The
      German Federal Ministry of Health will attach special importance to social
      medicine within the framework of forth-coming reforms in medical education for
      German doctors.

PMID- 8298221
TI  - [Concrete goals of the licensing regulation in social medicine education based on
      legal educational requirements].
AB  - The compilations of educational objectives known as "Gegenstandskataloge" link
      the global educational goals of the German licensing regulations and the more
      specific demands of the multiple-choice examinations. Favouring formerly the
      concept of operationalised educational objectives, the procedure is now
      restricted to the definition of medical subjects on which the examinations are
      based. The procedure of defining sociomedical objectives as part of the revised
      "Gegenstandskatalog" is described. More or less desired "side effects" and the
      representation and integration of sociomedical goals in the medical curriculum
      are discussed.

PMID- 8298222
TI  - [Social medicine in medical education exemplified by the Witten/Herdecke
      University].
AB  - In 1992 a problem-based curriculum was introduced into the Medical Faculty of the
      University of Witten/Herdecke (UWH). First experiences with this approach
      indicate that--for several reasons discussed--community related health issues
      have not been sufficiently addressed. Therefore, it is recommended to give
      students access to field experiences in community health. At the UWH this is
      accomplished by a community-related practicum which connects students with a
      variety of community health services. A parallel course discusses students'
      experiences in a problem based manner and population related studies are
      developed.

PMID- 8298223
TI  - [Social medicine within the frame work of a planned model medical curriculum of
      the Rudolf Virchow University Clinic of the Berlin Free University].
AB  - The planning group "Reformed Study Course in Medicine" at the Rudolf Virchow
      Clinical Centre of the Free University of Berlin presented in 1992 a draft of a
      model curriculum with particular emphasis on sociomedical aspects. As German
      statutory sickness insurance sets great store by getting the patient to go to his
      "family doctor" first before consulting a specialist ("primararztliche
      Orientierung"), sociomedical aspects have now assumed greater importance than
      previously. Sociomedically relevant professional series of events within the
      framework of the model curriculum are presented with particular reference to a
      continual integration of theory and practice by means of so-called "practice
      days" and "investigations into the professional activities of a doctor in
      general". Principal topics and teaching and learning goals governing the
      individual semester are exemplified.

PMID- 8298224
TI  - [Social medicine within medical education--experience abroad].
AB  - The trend to classify ("teaching" of social medicine more within the framework of
      development of primary or community-based health care is described. The apparent
      inefficiency of theoretical (lecture-based) presentation of social medicine asks
      for more weight to combine such a course with practical experience in the field
      of community-based health care. The growing importance of associations like the
      NETWORK (Community Oriented Educational Institutions for the Health Sciences) and
      of the International Clinical Epidemiology Network (INCLEN) is discussed.

PMID- 8298225
TI  - [Requirements for graduates of training courses from the viewpoint of different
      specialties. Health politics and specialty organization of various areas].
AB  - The main subjects of health politics in the "Lander", their methods and
      instruments are pointed out. Possible areas of workplaces for public-health
      degrees are exemplified.

PMID- 8298226
TI  - [Requirements for graduates of training courses from the viewpoint of various
      specialty fields].
AB  - This article describes the activities of the public health service in Germany,
      illustrated by means of practical examples. The interaction with other relevant
      organisations, particularly the health system, is described and the requirements
      of the examinations in public health.

PMID- 8298227
TI  - [Requirements for graduates of training courses from the viewpoint of various
      specialty fields].
AB  - By imparting competence in social medicine in the interdisciplinary course of
      studies "Public Health" graduates should be enabled to support social health
      insurance in finding adequate solutions regarding medical and economic aspects
      within the scope of planning and forming structures of health care. Thereby
      rationality in medical care can be increased so that rationing is avoided and
      reserves in efficiency and be mobilised.

PMID- 8298228
TI  - Surgical treatment of achalasia: a retrospective comparative study.
AB  - A retrospective study carried out on 74 patients among 101 consecutive cases of
      achalasia of the esophagus operated from 1967 to 1989 is reported. On 21 patients
      observed between 1967 and 1975, a standard transabdominal Heller cardiomyotomy
      was performed (group A). From 1976 to 1989, the treatment of choice was a Heller
      myotomy associated with a modified Dor's fundoplication. In 80 consecutive cases
      (group B) the extension of myotomy was regulated by intraoperative monitoring of
      lower esophageal sphincter pressure. A 5-year follow-up with questionnaires,
      physical examination, and barium swallows was carried out on 16 patients in group
      A and on 58 patients in group B. In 75.6% of the cases (56 patients) follow-up
      examinations included esophageal manometry and 24-hour esophageal pH monitoring.
      Recurrence of dysphagia was recognized in 3 cases in group A (18.7%) and in 2
      cases in group B (3.4%) (P = 0.053); postoperative gastroesophageal reflux,
      measured as a percentage of total reflux time, showed a significantly lower mean
      value in group B than in group A (1.8% vs. 4.1%, P < 0.01). This study suggests
      that an anti-reflux procedure lowers postoperative gastroesophageal reflux after
      Heller myotomy. Due to the low incidence of postoperative reflux and the
      negligible recurrence of dysphagia, Heller myotomy associated with a modified
      Dor's fundoplication may represent the surgical treatment of choice for achalasia
      of the esophagus.

PMID- 8298229
TI  - The trans-sphincteric and trans-sacral approaches for the surgical excision of
      rectal and presacral lesions.
AB  - In the decade from 1981 to 1990, 30 patients underwent a posterior transsacral
      approach at the Aichi Medical University Hospital for their benign or malignant
      rectal lesions. The operation was classified into two procedures, consisting of
      the transsphincteric approach and transsacral approach, in order to cope with the
      condition of the anal sphincter muscles; whether they were divided or not. Eleven
      rectal tumors were successfully excised through the opened-up rectum by using the
      transsphincteric approach, and excellent results were obtained without any
      postoperative complications. Using the transsacral approach, 2 presacral dermoid
      cysts and 11 rectal lesions were easily removed under direct vision. Their
      prognoses were excellent. The transsacral approach was also applied for the
      resection of recurrent rectal cancers after a radical, abdominoperineal resection
      in 6 patients suffering from intolerable local symptoms. All the patients were
      free from these uncomfortable local symptoms after the surgery. The posterior
      transsacral operation is thus considered to be of value not only for resecting
      benign rectal and presacral lesions, but also for resecting malignant rectal
      tumors in frail subjects who are unfit for radical operation and/or recurrent
      rectal cancer.

PMID- 8298230
TI  - The use of bioelectrical impedance analysis for monitoring body composition
      changes during nutritional support.
AB  - Body composition was measured with bioelectric impedance analysis (BIA) in 30
      patients with protein malnutrition following biliopancreatic diversion.
      Determinations were carried out prior to, during, and at the completion of
      intravenous nutritional support when the nutritional parameters had completely
      reverted to normal. Before treatment, body weight (BW), lean body mass (LBM), and
      body fat (BF) values were similar to those of controls, whereas the total body
      sodium/total body potassium (TBNa/TBK) and extracellular mass/body cell mass
      (ECM/BCM) ratios were considerably higher. During the support, no changes in BW,
      LBM, and BF were demonstrated, although a sharp decrease of TBNa/TBK and ECM/BCM
      was observed, thus demonstrating improved LBM composition. At the end of
      parenteral feeding, the BW, LBM, and BF values were similar to those observed
      before the support, while a further decrease in TBNa/TBK and ECM/BCM demonstrated
      a recovery towards normal of body composition. The full correspondence between
      clinical and BIA findings therefore suggests that this method may be valuable for
      monitoring body composition changes during nutritional support.

PMID- 8298231
TI  - Open and closed suction drainage after hepatic resection.
AB  - A retrospective study was conducted to compare open conduit drains with closed
      suction drains, with regard to the occurrence of intraperitoneal septic
      complications after hepatectomy (IPSCH). The subjects comprised 50 consecutive
      Japanese patients who underwent hepatic resection followed by the insertion of a
      closed suction drain and the control group comprised 50 patients in whom a simple
      conduit drain had been placed following liver surgery. There were no significant
      differences between the two groups in sex, age, underlying liver disease, or the
      type of hepatectomy performed; nor was there a significant difference in the
      incidence of IPSCH, the simple conduit drain group versus the closed suction
      drain group being (10% versus 8%, respectively). However, bile leakage was highly
      related to IPSCH, the incidence being 60% and 100% in the simple conduit drain
      and closed suction drain groups, respectively. Thus, to prevent IPSCH, the
      treatment of bile leakage is a much more important factor than the type of drain
      used.

PMID- 8298232
TI  - The significance of preoperative chemotherapy for early gastric carcinoma.
AB  - In order to achieve a complete prognosis for early gastric carcinoma, a greater
      effort must be made to improve its present treatment, considering the small
      percentage of patients who still die from recurrence despite the prompt
      initiation of surgery. Over the past 9 years, 26 patients with early gastric
      carcinoma have undergone surgical resection after receiving preoperative
      chemotherapy in the form of oral 5-FU or 5'-DFUR in our institute. The
      effectiveness of preoperative chemotherapy was evaluated by histopathological
      examination of the resected stomachs. Of a total of 24 patients with depressed
      type gastric cancer, 19 were histologically found to have a cancerless area
      within the cancerous lesion, 8 of whom were classified as being over Grade 1b.
      Gross changes were observed in 13 of these 24 patients. The frequency of multiple
      early gastric cancer occurring in patients who had not received chemotherapy was
      11.6%, whereas in those who had received chemotherapy it was 3.8%. The findings
      of this study thus indicate that preoperative chemotherapy is useful for reducing
      minute cancer foci and microscopic metastatic lesions.

PMID- 8298233
TI  - The significance of methicillin-resistant Staphylococcus aureus infection in
      general surgery: a multivariate analysis of risk factors and preventive
      approaches.
AB  - To investigate the characteristics, risk factors, and prevention of methicillin
      resistant Staphylococcus aureus (MRSA), a total of 3,627 patients were studied.
      Among these, 1,336 patients with various infections were used in a risk factor
      analysis of MRSA to determine the relationship between the use of antibiotics and
      the incidence of MRSA. Only 3.0% of infections were attributed to MRSA, the
      esophagus and colorectal region being highly involved, as anastomotic or pelvic
      abscesses, while the lung had a lower incidence. Almost half the patients with
      MRSA infections (47.6%) had concomitant infection. A univariate analysis revealed
      the following significant factors: The coexistence of gastrointestinal or
      metastatic malignancy, sepsis, tracheostomy, and the prior use of antibiotics
      such as the beta-lactam compounds or aminoglycosides. A multivariate analysis
      showed that gastrointestinal malignancy, sepsis, and the prior use of
      aminoglycosides, tetracycline, macrolides, and carbapenems were independently
      significant factors. To promote the education of doctors and nurses, regular in
      service meetings on MRSA were held in the ward. Moreover, preventive approaches
      such as patient isolation, strategically placed hand washing equipment, and the
      use of disposable gloves and contaminated waste bags, have been initiated, and
      the incidence of MRSA has decreased significantly since then. Thus, to control
      MRSA, the following steps should be taken: (1) constant and careful surveillance,
      (2) regular risk factor analyses, (3) the optimal administration of antibiotics,
      and (4) the education of all hospital staff.

PMID- 8298234
TI  - Shock-reinfusion injury to the central organs and the effect of free radical
      scavengers in the rat.
AB  - Hemorrhagic shock-reinfusion injury produces critical changes in various organs
      with the generation of oxidant-free radicals. Some papers have reported that
      shock-reinfusion injury to the intestine is effectively reduced by the scavengers
      of free radicals; however, few reports mention the central organ damage caused by
      systemic hemorrhagic shock-reinfusion injury. Using a rat systemic hemorrhagic
      shock model, injury to the central organs, being the brain, heart, lungs, liver,
      and kidneys was assessed by measuring malondialdehyde (MDA). The MDA levels in
      the lungs, kidneys, and liver were elevated significantly after reinfusion,
      although there was no elevation of MDA in the brain or heart. These data show
      that the lungs, liver, and kidneys are easily damaged by shock-reinfusion, but
      that the brain and heart are relatively resistant. The efficacy of the free
      radical scavengers, superoxide dismutase plus catalase and allopurinol, were
      evaluated 30 min after reinfusion. Pathological examination showed that
      superoxide dismutase plus catalase and allopurinol reduced reinfusion injury in
      the lungs, liver, and kidneys. Moreover, superoxide dismutase plus catalase
      reduced MDA levels in both the liver and kidneys, whereas allopurinol reduced MDA
      levels only in the kidneys after reinfusion. However, these free radical
      scavengers could not suppress the elevation of MDA in the lungs after reinfusion.

PMID- 8298235
TI  - A comparison of the metabolic changes after the distal splenocaval and portacaval
      shunts.
AB  - The distal splenorenal shunt (DSRS) is the recommended procedure for selective
      variceal decompression, but its use may be limited in patients who have undergone
      left nephrectomy, those with an anatomically aberrant relationship between the
      splenic and left renal veins, and those whose preoperative angiographic findings
      suggest a risk of developing postoperative renal vein hypertension. For these
      clinical situations, the selective distal splenocaval shunt (DSCS) is a useful
      alternative to the DSRS. However, the metabolic consequences of the DSCS have not
      yet been studied in detail and therefore, using a canine model, the metabolic
      changes following the DSCS and the portacaval shunt (Eck) were compared. The
      metabolic changes observed following the Eck were hyperammonia and amino acid
      imbalance, while those following the DSCS were similar to those of the control
      dogs. In terms of the hepatic adenosine triphosphate level, which reflects
      hepatic mitochondrial function, the DSCS dogs were also similar to the control
      dogs. These data suggest that there was no metabolic disadvantage of the DSCS
      compared to the control.

PMID- 8298236
TI  - Left ventricular diastolic function of the reperfused postischemic donor heart.
AB  - This study examined the pathophysiological relationship between left ventricular
      diastolic function and myocardial biochemical changes during reperfusion
      following hypothermic cardioplegic preservation of the donor heart. Isolated
      canine hearts (n = 47) were preserved for 6 h at 5 degrees C, followed by
      normothermic reperfusion for 2 h. Regression analysis demonstrated a highly
      significant correlation between: Left ventricular maximum -dp/dt and the left
      ventricular end-diastolic pressure (r = -0.56, P = 0.001); myocardial
      concentrations of adenosine triphosphate (ATP) and Ca2+ (r = -0.59, P = 0.0001);
      maximum -dp/dt and myocardial concentrations of: (1) ATP, (2) Ca2+, and (3) total
      adenine nucleotide with left ventricular volume loading (r = -0.53, P = 0.003; r
      = 0.51, P = 0.002; and r = 0.52, P = 0.002, respectively); and left ventricular
      end-diastolic pressure and myocardial Ca2+ (r = 0.66, P = 0.0001). These results
      suggest that left ventricular relaxation, as assessed by maximum -dp/dt, has a
      negative correlation with left ventricular stiffness, as determined by the end
      diastolic pressure in preserved donor hearts. Furthermore, increased myocardial
      Ca2+ concentrations reflect exhaustion of myocardial ATP. Thus, the myocardial
      Ca2+ concentration correlates directly with wall stiffness and inversely with
      ventricular relaxation, while ATP concentration correlates directly with
      ventricular relaxation.

PMID- 8298237
TI  - The relationship between the expression of blood group-related antigens and the
      cell proliferation of pancreatic carcinomas induced by N-nitrosobis(2
      oxopropyl)amine in hamsters.
AB  - The relationship between expression of blood group-related antigens (BGRAs) A, B,
      H, and cell proliferation was investigated during pancreatic carcinogenesis and
      in transplanted pancreatic carcinomas induced by N-nitrosobis(2-oxopropyl)amine
      in hamsters. Immunohistochemical staining was performed using monoclonal
      antibodies (MoAbs) against BGRAs A, B, H, and bromodeoxyuridine (BrdU). The
      labeling index (LI) was determined as the ratio of the number of BrdU-labeled
      cells to the total number of cells counted in each lesion. During carcinogenesis,
      the LI was observed to increase in line with the increase in the extent of
      atypism (P < 0.01). The mean LIs of the hyperplasia, atypical hyperplasia, and
      carcinoma were 0.32, 3.21, and 10.2, respectively. The mean LIs of transplanted
      carcinomas were higher than those of the original carcinomas (P < 0.01). The
      reactivity with each of the antibodies was determined using an arbitrary scoring
      system. Staining with MoAbs A and B (staining intensity; 1+ to 3+) appeared to be
      more intense than that with MoAb H (1+ to 2+) during carcinogenesis. Regarding
      the growth rate, which was very high, in the transplanted carcinomas, MoAb A
      reacted with all the cancer cells (4+), whereas, MoAbs B and H reacted with fewer
      cells (1+ to 3+). These results indicate that the A antigen in particular is
      associated with the cell proliferation of pancreas, especially with carcinoma
      induced in hamsters.

PMID- 8298238
TI  - Giant benign mesenchymoma of the mediastinum causing superior vena cava syndrome:
      report of a case.
AB  - The surgical resection of a giant primary mediastinal mesenchymoma causing
      superior vena cava syndrome is herein described. A 53-year-old man was admitted
      to the hospital complaining of severe dyspnea. A chest roentgenogram showed a
      large mediastinal mass shadow compressing the superior vena cava. At surgery, a
      yellow tumor measuring 27 x 25 x 12 cm and weighing 3,620 g was resected. The
      histological diagnosis was benign mesenchymoma. The patient's postoperative
      course was uneventful with a successful resolution of his superior vena cava
      syndrome.

PMID- 8298239
TI  - An adult case of bleeding Meckel's diverticulum diagnosed by preoperative
      angiography.
AB  - A 19-year-old woman in her 6th month of pregnancy was admitted to our hospital
      after passing a massive bloody stool. Romanoscopy and upper gastrointestinal
      panendoscopy revealed no abnormality, but a superior mesenteric arteriography
      demonstrated an embryonic artery with the extravasation of contrast medium in the
      distal end of the ileal artery. After the diagnosis of a bleeding Meckel's
      diverticulum had been established, an emergency operation was successfully
      performed. At laparotomy, a Meckel's diverticulum was found, about 70 cm toward
      the oral side from the ileocecal valve, and part of the ileum, including the
      diverticulum, was resected. Histological examination indicated that the
      diverticulum had a normal ileal layer with ectopic gastric mucosa and pancreatic
      tissue. Furthermore, multiple ulcers were observed in the adjacent ileum. Blood
      coagulation was observed at the site of one of these ulcers, and this was
      presumed to be the source of the hemorrhage.

PMID- 8298240
TI  - Combination of preoperative lymphangiography using lipiodol and intraoperative
      lymphangiography using Evans Blue facilitates the accurate identification of
      postoperative chylous fistulas.
AB  - In a 61-year-old woman who underwent extensive retroperitoneal lymph node
      dissection for rectal cancer, postoperative chylous ascites developed. The site
      of the lymphatic leak was evident on the lymphangiogram with lipiodol taken prior
      to the surgical repair of the leak, and another site seen on the intraoperative
      lymphangiogram using Evans Blue. A direct surgical repair led to good results.
      Therefore, the combination of pre- and intraoperative lymphangiography
      facilitates the successful surgical management of rare but alarmingly dangerous
      postoperative chylous ascites.

PMID- 8298241
TI  - Thoracoscopic pulmonary resection in two cases using an endoscopic linear stapler
      and loop ligature.
AB  - Recent advances in rigid endoscopic imaging capabilities, light sources, and
      instrumentation have dramatically expanded the potential role of laparoscopic and
      thoracoscopic surgery. Moreover, the recent introduction of an endoscopic linear
      stapling device and loop ligature has made thoracoscopic pulmonary resection
      possible. We present herein two cases of peripheral pulmonary lesions which were
      resected thoracoscopically. Case 1 was a 19-year-old man with a history of
      recurrent pneumothorax due to a left apical bulla who underwent thoracoscopic
      lung resection using a new stapling device, and Case 2 was a 46-year-old man with
      a small pulmonary lesion on the left basal segment (S8) who underwent
      thoracoscopic lung resection using loop ligature. Postoperatively, there was no
      evidence of air leak in either patient and both were discharged 6 days after
      surgery. The technical procedures for thoracoscopic lung resection and the
      clinical courses of both patients are described in this paper.

PMID- 8298242
TI  - Reconstruction of jugular and portal blood flows using remodeled great saphenous
      vein grafts.
AB  - Remodeled great saphenous vein grafts were used to reconstruct both jugular and
      portal veins. The great saphenous vein was split longitudinally and sutured side
      to-side to construct a vessel twice the diameter and one half the length of the
      original vessel. This graft was used with good results for reconstruction of the
      jugular veins in a patient after a bilateral neck dissection for tongue cancer
      and for a portal vein in a patient after resection for cancer in the head of the
      pancreas.

PMID- 8298243
TI  - Structure and biological functions of keratan sulfate proteoglycans.
AB  - The skeletal and corneal keratan sulfate proteoglycans show a different metabolic
      and structural heterogeneity. The domain structure of the carbohydrate chain has
      been shown to be different in various animal species. There are two major types
      of skeletal keratan sulfate proteoglycans with and without fucose. The protein
      cores of the corneal chicken keratan sulfate proteoglycan (lumican) and those of
      another small keratan sulfate proteoglycan (fibromodulin) have been sequenced.
      Keratan sulfate oligosaccharides belong to the members of an antigen family of
      the poly-N-acetyllactosamine series. Monoclonal antibodies and immunoassay
      procedures for keratan sulfate proteoglycans have been prepared. In
      osteoarthritis, no significant specific increase of keratan sulfate has been
      found. Keratan sulfate is a functional substitute for chondroitin sulfate in O2
      deficient tissues.

PMID- 8298244
TI  - Proteoglycans of basement membranes.
AB  - Proteoglycans carrying either heparan sulfate and/or chondroitin sulfate side
      chains are typical constituents of basement membranes. The most prominent
      proteoglycan (perlecan) consists of a 400-500 kDa core protein and three heparan
      sulfate chains. Electron microscopy and cDNA sequencing show a complex and
      elongated domain structure for the core protein which in part is homologous to
      that of the laminin A chain. This structure may be varied by alternative splicing
      and proteolysis. Integration into basement membranes probably occurs by heparan
      sulfate binding to laminin and collagen IV, core protein binding to nidogen and
      by limited self assembly. The proteoglycan is in addition a cell-adhesive protein
      which is recognized by beta 1 integrins. Several more proteoglycans with smaller
      core proteins (10-160 kDa) apparently exist in basement membranes but are less
      well characterized. Biological functions include control of filtration through
      basement membranes and binding of growth factors and protease inhibitors.

PMID- 8298245
TI  - Nervous tissue proteoglycans.
AB  - The structure, biosynthesis, localization, and possible functional roles of
      nervous tissue glycosaminoglycans and proteoglycans were last reviewed several
      years ago. Since that time, there has been an exponential increase in
      publications on the neurobiology of proteoglycans. This review will therefore
      focus on reports which have appeared in the period after 1988, and especially on
      those concerning the properties of individual characterized nervous tissue
      proteoglycans. Related areas such as the regulation of glycosaminoglycan
      biosynthesis and the roles of cell surface proteoglycans in adhesion and growth
      control are covered in other contributions to this special topic issue.

PMID- 8298246
TI  - Proteoglycans and hyaluronan in female reproductive organs.
AB  - Proteoglycans and hyaluronan have been isolated from various female reproductive
      organs and fetal membranes. Special attention has been directed to changes in the
      composition of these molecules in the tissue during pregnancy and ovulation.
      Various chondroitin sulfate/dermatan sulfate proteoglycans, which represent
      extracellular matrix proteoglycans, are closely related to the organization of
      connective tissues. Heparan sulfate proteoglycans are widely distributed on the
      plasma membrane of most mammalian cells including those in the female
      reproductive organs. They are involved in various aspects of cell-to-cell or cell
      to-extracellular matrix interactions. Although the precise biological functions
      of these proteoglycans are not currently clear, recent advances in biochemistry
      and molecular biology techniques promise an exciting new development in this
      area.

PMID- 8298247
TI  - Altered proteoglycan gene expression and the tumor stroma.
AB  - Tumor stroma is a specialized form of tissue that is associated with epithelial
      neoplasms. Recent evidence indicates that significant changes in proteoglycan
      content occur in the tumor stroma and that these alterations could support tumor
      progression and invasion as well as tumor growth. Our main hypothesis is that the
      generation of tumor stroma is under direct control of the neoplastic cells and
      that, via a feedback loop, altered proteoglycan gene expression would influence
      the behavior of tumor cells. In this review, we will focus primarily on the work
      from our laboratory related to the altered expression of chondroitin sulfate
      proteoglycan and its role in tumor development and progression. The connective
      tissue stroma of human colon cancer is enriched in chondroitin sulfate and the
      stromal cell elements, primarily colon fibroblasts and smooth muscle cells, are
      responsible for this biosynthetic increase. These changes can be reproduced in
      vitro by using either tumor metabolites or co-cultures of human colon carcinoma
      cells and colon mesenchymal cells. The levels of decorin, a leucine-rich
      proteoglycan involved in the regulation of matrix assembly and cell
      proliferation, are markedly elevated in the stroma of colon carcinoma. These
      changes correlate with a marked increase in decorin mRNA levels and a concurrent
      hypomethylation of decorin gene, a DNA alteration associated with enhanced gene
      expression. Elucidation of decorin gene structure has revealed an unexpected
      degree of complexity in the 5' untranslated region of the gene with two leader
      exons that are alternatively spliced to the second coding exon. Furthermore, a
      transforming growth factor beta (TGF-beta)-negative element is present in the
      promotor region of decorin gene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298248
TI  - Cytokines and proteoglycans.
AB  - Cytokines play an important regulatory role in the metabolism of proteoglycans.
      Proteoglycans are found in plasma membranes, but predominantly in the extra
      cellular matrix. In the latter they are quantitatively and qualitatively
      essential components. Especially in a tissue like cartilage without any blood
      vessels, the cells are dependent on cytokines for the communication among
      themselves in the extra-cellular matrix and also for communication with the
      'outside world'. Various cytokines have been found to be able to penetrate the
      extra-cellular matrix and inhibit, respectively stimulate the proteoglycan
      synthesis. Also, the degradation of proteoglycans can be stimulated, respectively
      inhibited by several cytokines. In addition, some cytokines have been found which
      regulate the effects of the other cytokines. With respect to proteoglycan
      metabolism a complex cytokine network is emerging. Furthermore it is becoming
      increasingly clear that proteoglycans are connected to the cytokine network by
      their own bioactive functions. First, they possibly possess cytokine activities
      themselves. Second, they can function as receptors, protectors, inactivators and
      storage ligands for cytokines. So the proteoglycans are clearly involved in the
      feedback signalling from the extra-cellular matrix to the cells that are
      synthesizing this extra-cellular matrix. Together with agonistic or antagonistic
      cytokines they are involved in the regulation of proteoglycan turnover during
      balanced or unbalanced metabolism in normal, respectively pathological
      situations.

PMID- 8298249
TI  - Glycosaminoglycans, proteoglycans and aging.

PMID- 8298250
TI  - A brief history of proteoglycans.

PMID- 8298251
TI  - Molecular cloning and analysis of the protein modules of aggrecans.
AB  - The large aggregating chondroitin sulfate proteoglycan of cartilage, aggrecan,
      has served as a prototype of proteoglycan structure. Molecular cloning has
      elucidated its primary structure and revealed both known and unknown domains. To
      date the complete structures of chicken, rat and human aggrecans have been
      deduced, while partial sequences have been reported for bovine aggrecan. A
      related proteoglycan, human versican, has also been cloned and sequenced. Both
      aggrecan and versican have two lectin domains, one at the amino-terminus which
      binds hyaluronic acid and one at the carboxyl-terminus whose physiological ligand
      is unknown. Both lectins have homologous counterparts in other types of proteins.
      Within the aggrecans the keratan sulfate domain may be variably present and also
      has a prominent repeat in some species. The chondroitin sulfate domain has three
      distinct regions which vary in their prominence in different species. The complex
      molecular structure of aggrecans is consistent with the concept of exon shuffling
      and aggrecans serve as suitable prototypes for comprehending the evolution of
      multi-domain proteins.

PMID- 8298252
TI  - The link proteins.
AB  - Aggregates of chondroitin-keratan sulfate proteoglycan (aggrecan) and hyaluronic
      acid (hyaluronan) are the major space-filling components of cartilage. A
      glycoprotein, link protein (LP; 40-48 kDa) stabilizes the aggregate by binding to
      both hyaluronic acid and aggrecan. In the absence of LP, aggregates are smaller
      (as estimated by rotary shadowing of electron micrographs) and less stable (they
      dissociate at pH 5) than they are in the presence of LP. The proteoglycan
      aggregate, including LP, is dissociated in the presence of chaotropes such as 4 M
      guanidine hydrochloride. On removal of the chaotrope, the complex will
      reassociate. This forms the basis of the isolation of LP from cartilage and has
      been described in detail elsewhere. Tryptic digestion of the proteoglycan
      aggregates results in a high molecular weight product that consists of hyaluronic
      acid to which is bound LP and the N-terminal globular domain of aggrecan
      (hyaluronic acid binding region; HABR) in a 1:1 stoichiometry. The amino acid
      sequences of LP and HABR are surprisingly similar. The amino acid sequence can be
      divided into three domains; an N-terminal domain that falls into the
      immunoglobulin super-family and two C-terminal domains that are similar to each
      other. The DNA structure echoes this similarity, in that the major domains are
      reflected in three separate exons in both LP and HABR. The two C-terminal domains
      are largely responsible for the association with HA and are related to two
      recently described hyaluronate-binding proteins, CD44 and TSG-6. A variety of
      approaches, including analysis of the forms of LP in vivo, rotary shadowing and
      analysis of the sequence in the immunoglobulin-like domain, have shed
      considerable light on the structure-function relationships of LP. This review
      describes the structure and function of LP in detail, focusing on what can be
      inferred from the similarity of LP, HABR and related molecules such as
      immunoglobulins and lymphocyte HA-receptors.

PMID- 8298253
TI  - Small proteoglycans.
AB  - In this review the structure and functions of two non-related proteoglycan
      families are discussed. One family represents a group of extracellular matrix
      macromolecules characterized by core proteins with leucine-rich repeat motifs.
      Within this family special attention is given to those members which carry
      chondroitin or dermatan sulfate glycosaminoglycan chains. The second family is
      characterized by repeat sequences of serine and glycine. Their members are
      products of a single core protein gene and are characteristic constituents of
      secondary vesicles in cells of the haematopoietic lineage.

PMID- 8298255
TI  - AHNA certificate program in Holistic nursing courses.

PMID- 8298254
TI  - Isolation and purification of proteoglycans.
AB  - Purification of a protein typically involves development of a quantitative assay
      to track protein integrity (e.g. enzyme activity) during subsequent isolation
      steps. The generalized procedure involves choosing the source of the protein,
      defining extraction conditions, developing bulk purification methods followed by
      refined, more selective methods. The purification of proteoglycans is often
      complicated by a) limited source quantities, b) necessity of chaotrophic solvents
      for efficient extraction, c) their large molecular size and d) lack of defined
      functions to enable purity (i.e. activity, conformation) to be assessed. Because
      the usual goal of proteoglycan purification is physical characterization (intact
      molecular weight, core protein and glycosaminoglycan class and size), the
      problems of a suitable assay and/or native conformation are avoided. The 'assay'
      for tracking proteoglycan isolation typically utilizes uronic acid content or
      radiolabel incorporation as a marker. Once extracted from their
      cellular/extracellular environment, proteoglycans can be isolated by density
      gradient centrifugation and/or column chromatography techniques. Recent advances
      in the composition of chromatographic supports have enabled the application of
      ion-exchange, gel permeation, hydrophobic interaction and affinity chromatography
      resins using efficient high-pressure liquid chromatography to proteoglycan
      purification.

PMID- 8298256
TI  - The power of one.

PMID- 8298257
TI  - An energetic healing success story.

PMID- 8298258
TI  - Mild hypothermia and cerebral metabolism.

PMID- 8298259
TI  - Incidence and perioperative management of tension pneumocephalus following
      craniofacial resection.
AB  - This study is a retrospective review to evaluate factors associated with the risk
      of pneumocephalus following craniofacial resection and the management of tension
      pneumocephalus. Twenty-two craniofacial operative procedures were reviewed in 18
      patients entered into the Neurosciences Critical Care Unit, Johns Hopkins
      Hospital, during a 54 month period, from 1986-1991. Pneumocephalus developed
      after 7 of 22 operations; of these seven, two developed tension pneumocephalus.
      The use of lumbar cerebral spinal fluid (CSF) drainage during the operation
      correlated most strongly with the development of pneumocephalus. The diagnosis of
      esthesioblastoma also correlated significantly. Both episodes of tension
      pneumocephalus occurred after craniofacial resection in which lumbar drainage of
      CSF was performed. Tension pneumocephalus was successfully treated in these two
      patients with a combination of air evacuation and medical management of raised
      intracranial pressure. Transient diabetes insipidus developed in both patients.
      The risk of pneumocephalus following craniofacial procedures is significant, and
      may be increased by the use of lumbar drainage of CSF intraoperatively. Rapid
      neurologic deterioration following craniofacial resection may be caused by the
      development of tension pneumocephalus. Early diagnosis of tension pneumocephalus
      and aggressive management of raised intracranial pressure may be important in
      preventing serious neurological complications.

PMID- 8298260
TI  - Incidence and clinical significance of hemidiaphragmatic paresis in patients
      undergoing carotid endarterectomy during cervical plexus block anesthesia.
AB  - This study was designed to investigate the incidence and clinical consequences of
      hemidiaphragmatic paresis in patients undergoing carotid endarterectomy using
      cervical plexus block anesthesia. In 28 patients, diaphragmatic motion was
      evaluated by fluoroscopy 20 min after cervical plexus block with 1% mepivacaine.
      In 61% of the patients abnormalities of diaphragmatic motion were detected. These
      motion anomalies were associated with a statistically significant elevation of
      PaCO2. Gender, age, and whether the block was on the left or right side did not
      appear to affect the incidence of motion abnormalities after cervical plexus
      block anesthesia.

PMID- 8298261
TI  - Cerebral blood flow, plasma catecholamines, and electroencephalogram during
      hypoglycemia and recovery after glucose infusion.
AB  - Regional cerebral blood flow (rCBF) and plasma catecholamines were measured in
      separate experiments during the onset of insulin-induced hypoglycemia and during
      recovery. The purpose of these experiments was twofold: first, to study the
      relationship between plasma catecholamines and rCBF to determine if increased
      concentrations of plasma catecholamines were responsible for the increase in rCBF
      observed during insulin-induced hypoglycemia, and second, to study changes in
      rCBF after recovery from hypoglycemia. Male Long-Evans rats were fasted
      overnight, surgically prepared under isoflurane anesthesia, restrained, and
      allowed to awake from anesthesia. In the first series of experiments, plasma
      catecholamines, arterial blood pressure, arterial blood gases, and
      electroencephalogram (EEG) were measured during the onset of hypoglycemia
      produced by i.v. insulin and the recovery after i.v. glucose. The EEG showed a
      characteristic high-amplitude, slow-wave pattern during hypoglycemia (plasma
      glucose, 38 +/- 2 mg/dl; n = 3). Plasma epinephrine in the normoglycemic control
      rats was 529 +/- 122 pg/ml (n = 5) and increased 4.5 times as plasma glucose
      reached 50 +/- 3 mg/dl. After the initial increase, plasma epinephrine steadily
      decreased toward baseline over the next 90 min as the hypoglycemia became more
      severe. Plasma norepinephrine significantly increased by 60% when plasma glucose
      was 40 +/- 2 mg/dl and remained increased during much of the recovery period. In
      other studies, rCBF was measured in four groups of rats, one group with
      normoglycemia (control), one with hypoglycemia, one at 5 min of recovery, and one
      at 30 min of recovery. Regional CBF increased during hypoglycemia (plasma
      glucose, 39 +/- 1 mg/dl; n = 6) in most regions studied and ranged from 28 to 99%
      above control. After 5 min of the recovery (plasma glucose, 269 +/- 15 mg/dl),
      rCBF returned to or decreased below baseline. In a previous study, we determined
      that rCBF did not increase during hypoglycemia until plasma glucose decreased to
      40 mg/dl. In the present study, the peak increase in plasma epinephrine occurred
      when plasma glucose was 50 mg/dl. At plasma glucose concentrations which rCBF
      began to increase, plasma epinephrine was decreasing from its peak level.
      Regional CBF and plasma norepinephrine increased in parallel during the onset of
      hypoglycemia; however, during the recovery period, plasma norepinephrine remained
      increased while rCBF decreased to or below baseline. The dissociation of rCBF and
      plasma catecholamines casts doubt on the hypothesis that plasma catecholamines
      are responsible for increases in rCBF.

PMID- 8298262
TI  - Venous air embolism after craniotomy closure: tension pneumocephalus implicated.
AB  - The authors present a case of venous air embolism occurring immediately upon skin
      closure after craniotomy in the prone position. This 5-year-old patient had a
      third ventricle tumor resected with bipolar cautery via a frontal trans-collosal
      approach into the lateral ventricle and through the foramen of Monroe. Doppler
      monitoring was utilized during the case since the patient's head was extended
      upwards in 10 degrees reverse Trendelenburg position. No air was detected during
      the operation. The ventricles were filled with saline presumably displacing air,
      prior to dural closure. However, with an increase in nitrous oxide from 55 to 68%
      prior to skin closure, venous air embolism was subsequently detected by Doppler
      and confirmed by end-tidal/arterial pCO2 gradient. The authors speculate that
      tension pneumocephalus caused the venous air embolism and describe the probable
      route of entry into the venous system.

PMID- 8298263
TI  - Measuring the burden of secondary insults in head-injured patients during
      intensive care.
AB  - Primary traumatic brain damage may be compounded by secondary pathophysiological
      insults that can occur soon after trauma, during transfer to hospital or
      subsequent treatment of the head-injured patient. The aim of this prospective
      study was to quantify the burden of a wide range of secondary insults occurring
      after head injury and to relate these to 12-month outcome. In 124 adult head
      injured patients studied during intensive care using a computerized data
      collection system, < or = 14 clinically indicated physiological variables were
      measured minute-by-minute. Verified values falling outside threshold limits for >
      or = 5 min, as defined by the Edinburgh University Secondary Insult Grading
      scheme, were analysed by insult grade and duration. A greater incidence of
      secondary insults was detected than previous studies have indicated. Insults were
      found in 91% of patients and occurred in all severities of head trauma, at all
      ages, and at every level of Injury Severity Score (ISS). The cumulative durations
      were much greater than previously recorded although 85% of the total time was at
      the least severe grade. Short duration insults were common. In 71 patients, in
      whom 8 insults could be assessed (intracranial pressure, arterial hypo- and
      hypertension, cerebral perfusion pressure, hypoxemia, pyrexia, brady- and
      tachycardia), outcome at 12 months was analysed using logistic regression to
      determine the relative influence of age, admission Glasgow Coma Sumscore, ISS,
      pupil response on admission, and insult duration on both mortality and morbidity.
      The most significant predictors of mortality in this patient set were durations
      of hypotensive (p = .0064), pyrexic (p = .0137), and hypoxemic (p = .0244)
      insults. When good versus poor outcome was considered, hypotensive insults (p =
      .0118) and pupil response on admission (p = .0226) were significant.

PMID- 8298264
TI  - Sciatic nerve palsy as a complication after acoustic neurinoma resection in the
      sitting position.
AB  - We present a case of sciatic neuropathy after operation in the sitting position.
      Sciatic nerve palsy as a complication of the sitting position appears to be
      extremely rare. The patient we describe was a short, plump woman. To attain
      optimal surgical exposure, a greater flexion of the hips than usual was utilized.
      That may explain the possible stretch injury of the sciatic nerve.

PMID- 8298265
TI  - Cerebral arteriovenous oxygen difference and lactate-oxygen index: a case of
      bilateral monitoring.
AB  - We report a case of ruptured cerebral aneurysm that had uneven bilateral cerebral
      arteriovenous oxygen differences and lactate oxygen indexes. Guidelines are
      offered for determining which side to choose for jugular bulb catheterization. We
      conclude that bilateral catheterization may be useful in patients with severe
      hemispheric damage.

PMID- 8298266
TI  - Purple glove syndrome.
AB  - Purple glove syndrome (PGS) often begins with discoloration and progresses to a
      petechial rash with induration or evidence of infiltration. The etiology of PGS
      is unknown, although various theories center around i.v. extravasation. We report
      a case of PGS in a child's foot associated with administration of Dilantin
      (phenytoin).

PMID- 8298267
TI  - The role of bloodletting in the prevention and treatment of asthenic apoplexy.

PMID- 8298268
TI  - Beneficial effects of hemodilution on cerebral microcirculation.

PMID- 8298269
TI  - Opsonization and phagocytosis of Cryptococcus neoformans.
AB  - Cryptococcus neoformans is unique among the pathogenic fungi because the yeast is
      surrounded by an antiphagocytic polysaccharide capsule. Host resistance to
      cryptococcosis is dependent on natural defense mechanisms that cope with this
      essential fungal virulence factor. Recent studies in several laboratories
      indicate that, under appropriate circumstances, the antiphagocytic activity of
      the capsule can be overcome. A reversal of the antiphagocytic properties of the
      capsule requires (i) activation of the alternative complement pathway by
      encapsulated cryptococci, leading to deposition of the opsonic ligand iC3b at the
      capsular surface, (ii) presence of essential cytokines which up-regulate the
      efficiency of complement-dependent phagocytosis, and (iii) availability of
      phagocytic cells whose complement receptors are capable of appropriate up
      regulation. Deficiencies in one or more components of the opsonization-phagocyte
      cytokine triad may account, in part, for several features of the pathogenesis of
      cryptococcosis as well as the susceptibility of some immunocompromised patients
      to cryptococcosis. It may be possible to overcome some deficiencies by passive
      immunization with anticapsular IgG which takes advantage of phagocyte Fc
      receptors that are constitutively competent for phagocytosis or by therapeutic
      use of cytokines that up-regulate complement-dependent phagocytosis.

PMID- 8298270
TI  - Interactions between human phagocytic cells and Histoplasma capsulatum.

PMID- 8298271
TI  - Experimental mycoses in congenitally immunodeficient rodents.
AB  - Congenitally immunodeficient rodents are playing a major role in clarifying host
      defense mechanisms and elucidating the virulence factors of a variety of mycotic
      agents. These murine models are also being used to study the histopathology and
      chemotherapy of a variety of fungal infections. Recent development of
      immunodeficient transgenic mice will make these murine models even more valuable
      for studies on the diagnosis, pathogenesis, immunity, and chemotherapy of fungal
      infections.

PMID- 8298272
TI  - Advances in experimental paracoccidioidomycosis using an isogenic murine model.
AB  - A genetically controlled murine model of paracoccidioidomycosis which allowed us
      to investigate several parameters of the host-parasite interactions was
      established in our laboratory. Natural resistance and acquired immune responses
      to P. brasiliensis infection were investigated employing resistant and
      susceptible mice infected with highly virulent or slightly virulent P.
      brasiliensis isolates. Resistant mice inoculated with a highly virulent P.
      brasiliensis isolate present efficient macrophage activation, presence of DTH
      response, low levels of specific antibody and a tendency to resolution of the
      infectious process, suggesting that a T helper-1 mode of immune response is
      mounted. Susceptible mice, on the contrary, seem to mount a predominantly T
      helper-2 type of immune response activation in which an inefficient macrophage
      activation, depressed DTH reactions and high levels of antibodies result in
      progressive disease. The crucial role of the fungal virulence on the outcome of
      the infection of susceptible and resistant mice is also demonstrated, thus
      reinforcing the idea that both the innate resistance of the host and the
      pathogenicity of the fungal cells are determinant on the outcome of the disease.
      This model is proposed as a framework of our current knowledge of the host
      parasite interactions in paracoccidioidomycosis and as a basis for future
      challenge in continuing analyses.

PMID- 8298273
TI  - Changes in membrane fluidity modulate heat shock gene expression and produced
      attenuated strains in the dimorphic fungus Histoplasma capsulatum.
AB  - In the dimorphic fungus Histoplasma capsulatum the expression of heat shock genes
      is modulated by addition of fatty acids. Addition at 25 degrees C of saturated
      fatty acid (palmitic acid) to mycelia of H. capsulatum induced a significant
      increase in heat shock mRNAs transcription when cells were heat shocked.
      Conversely, treatments with unsaturated fatty acid (oleic acid) drastically
      reduced the level of heat shock gene transcription at 37 degrees C, and no
      detectable levels were measurable with 2 mM. Addition of saturated fatty acid
      induced a thermotolerant state and mitochondria retained ATPase activity coupled
      to electron transport under severe heat shock conditions and shortened the time
      required for mycelium-to-yeast phase transition. Conversely, addition of
      unsaturated fatty acids uncoupled mitochondrial electron transport and prolonged
      considerably the time required for phase transition at the same temperatures. A
      virulent strain, if treated with unsaturated fatty acid under condition in which
      no heat shock was detectable, lost its virulence probably as a consequence of
      decreased ability to adapt to the new living condition present in the host.

PMID- 8298274
TI  - Cell cycle regulation of polymorphism in Wangiella dermatitidis.
AB  - Phenotypic switching in Wangiella dermatitidis between polarized growth processes
      leading to yeast budding or hyphal apical extension and nonpolarized processes
      leading to isotropically enlarged forms that may become multicellular is a cell
      cycle related phenomenon. Exit of yeasts from the budding growth cycle by this
      polymorphic agent of phaeohyphomycosis can be induced by incubation of wild-type
      (wt) cells in pH 2.5 medium at 25 degrees C, or of certain temperature-sensitive,
      cell-division-cycle (cdc) mutants at pH 6.5 at 37 degrees C. Continued incubation
      under these semirestrictive conditions causes yeasts to form unbudded,
      multinucleate, multicellular phenotypes that resemble the sclerotic bodies of
      chromoblastomycotic fungi. However, new results with Ca2+ indicate that at pH 2.5
      critical, but low, concentrations of this ion are crucial for regulating
      multicellular form development, higher concentrations allow maintenance of
      polarized growth, and that switching between polarized and nonpolarized growth
      may involve a Ca2+/proton exchange mechanism. Support for this important role for
      Ca2+ is provided by experiments with EGTA in media buffered against pH change at
      near neutrality. Under these conditions, withholding Ca2+ with high EGTA
      concentrations caused yeasts to arrest in a terminal phenotype characterized by
      the presence of a bud initial that tended not to enlarge. In contrast, lower
      concentrations of EGTA often induced yeast-to-multicellular-form conversion.
      Other new results have suggested that even brief culture of yeasts under
      conditions that arrest their budding growth cycles may induce commitment to
      phenotypic transitions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298275
TI  - The role of polyamines in fungal cell differentiation.
AB  - Polyamines are low molecular weight polycations which are present in all
      organisms, both procaryotic and eucaryotic (1). The most widely distributed
      polyamines are putrescine, spermidine and spermine; nevertheless, a large number
      of fungal species are devoid of spermine. Polyamines are essential for growth,
      and mutants affected in their synthesis become auxotrophic. Regarding their
      physiological roles, it has been demonstrated that polyamine starvation leads to
      reduction in the synthesis of nucleic acids and proteins. It has been concluded
      that polyamines are essential for macromolecule synthesis, although their precise
      mode of action remains unknown (2) (Table 1). Because of their net charge, it has
      been suggested that polyamines bind to macromolecular anions such as nucleic
      acids and phospholipids, stabilizing their structure. Levels of polyamines, as
      well as those of the first enzyme in the biosynthetic route: ornithine
      decarboxylase (ODC), increase during the phases of active growth and
      differentiation in distinct eucaryotic systems. In fungi the role of polyamines
      in cell differentiation remains debatable since no clear cut correlation between
      their levels and development has been demonstrated. This lack of correlation may
      be due to the fact that most polyamines present in the cell are inside the
      vacuole or bound to all polyanions, only a small amount remaining free to fulfill
      other tasks associated with development (3).

PMID- 8298276
TI  - Biochemical and physiological aspects in the dimorphism of Paracoccidioides
      brasiliensis.
AB  - Paracoccidioides brasiliensis is a dimorphic fungus pathogenic for humans. It
      shows a yeast like phase at 37 degrees C and a mycelial phase at 23 degrees C.
      Biochemical aspects of its dimorphism are related to the presence of hormone
      receptors, regulation of cAMP, or modulation of glucan synthetase activity
      through cytoplasmic proteinases. These aspects are reviewed herein.

PMID- 8298277
TI  - Cell wall antigens in Aspergillus fumigatus.
AB  - The Aspergillus cell wall contains most of the antigens secreted by the fungus
      during its active in vitro or in vivo growth. These antigens, which bind to the
      IgE and IgG of allergic and aspergilloma patients or are secreted in the
      biological fluids of patients with invasive aspergillosis, are of primary
      importance in the diagnosis of aspergillosis. Located at the interface between
      host and pathogen cells, the fungal cell wall plays a major role during fungal
      invasion. It contains several surface receptors involved in adhesion of the
      fungus to host proteins and cells. Some of the wall antigens are also directly
      involved in the colonization of the host tissues by the fungus. Very few of these
      putative virulence factors have been purified until now. A 33-kDa alkaline
      protease of the subtilisin family can hydrolyze several extracellular matrix
      proteins such as collagen, fibrinogen, elastin. However, gene disruption
      experiments have shown that protease-deficient mutants are still able to infect
      mice. An 18-kDa antigen, which has been detected in the urine of patients with
      invasive aspergillosis, is present in vivo in the lung of mice infected with A.
      fumigatus. It has a ribonuclease activity that cleaves a single phosphodiester
      bond in a highly conserved region of the ribosomal RNA. Its role in the virulence
      of A. fumigatus has not been demonstrated until now. Biochemical and molecular
      characterization of the wall antigenic aggressins should be pursued.

PMID- 8298278
TI  - Molecular interactions at the interface of Candida albicans and host cells.
AB  - The interaction of C. albicans with host cells has been shown to be quite
      complex. At least three recognition systems have been described, and, probably
      additional ones exist. The recognition systems are classified by the type of host
      cell, the growth form of the organism and the nature of the interaction at the
      molecular level, i.e., protein-protein or protein-oligosaccharide. It would
      appear that C. albicans has at least two distinct mannoprotein adhesins. One
      resembles a lectin in that it recognizes host cell glycosides containing fucose,
      and with some strains of C. albicans, N-acetylglucosamine. The second adhesin has
      properties similar to the integrin or transmembrane glycoproteins such as the CR3
      (complement receptor 3). Still to be resolved is the characterization of the
      lectin-like adhesin as well as the relationship of the CR2-like activity to the
      CR3 of Candida. A third adhesin which is a mannan polysaccharide has been
      suggested as a recognition molecule in the adherence of the organism to buccal
      epithelial cells.

PMID- 8298279
TI  - Identification of antigens of Coccidioides immitis which stimulated immune T
      lymphocytes.
AB  - T-cell mediated immune response to coccidioidomycosis has been shown to be the
      principal mechanism of resistance to this respiratory fungal disease in
      experimental animals. In this study, a Coccidioides immitis antigen-specific
      murine T-cell line was used to identify macromolecules capable of eliciting an
      immune mouse T-cell proliferative response. The murine T-cell line was selected
      on the basis of its strong positive response to a soluble conidial wall fraction
      (SCWF), which had previously been shown to be reactive in humoral and cellular
      immunoassays. An antigen-specific T-cell line rather than T-cell clones was used
      to identify multiple antigens. The T-cell immunoblot method was employed first to
      identify immunoreactive sub-fractions of the SCWF, and then to identify T-cell
      fusion proteins (FPs) obtained from a cDNA expression library constructed in
      lambda gt11. The library was screened with anti-SCWF. The nucleotide sequence of
      a 0.2 kilobase cDNA insert encoding a FP which elicited vigorous T-cell response
      was determined. A construct of this insert was subcloned into the pET expression
      vector system and 6.5-kilodalton (kDa) recombinant protein (RP) expressed in
      Escherichia coli was isolated. The RP and FP were shown to be homologous on the
      basis of identify of their amino acid sequences. Antibody raised in guinea pigs
      against the RP recognized a 59-kDa native protein of the mycelial culture
      filtrate produced by three separate strains of C. immitis, and reacted with the
      cell wall of arthroconidia as detected by immunofluorescence microscopy. In this
      study we have identified and partly characterized a potentially important T-cell
      stimulating antigen of C. immitis.

PMID- 8298280
TI  - Yeast exoglucanases. Where redundancy implies necessity.
AB  - Three exoglucanase genes have been described in Saccharomyces cerevisiae. The
      bulk of the exoglucanase (EXO) activity is encoded by the EXG1 gene, whose
      primary gene product is differentially glycosylated during its transit to the
      cell surface to yield three isoenzymes: EXOI, EXOII and EXOII1/2. EXOII, the
      major isoenzyme, carries two short oligosaccharides, each one consisting of an
      inner core with a single branch of the outer chain, attached to both potential
      glycosylation sites present in the molecule (Asn165 and Asn325). EXOI and
      EXOII1/2 are minor representatives. The second carries a single short sugar
      residue attached to Asn165 whereas the former elongate the outer chain of, at
      least, one oligosaccharide as other cell wall mannoproteins. The protein portion
      of the EXGI gene product is cleaved in Golgi by the Kex2 protease. A different
      exoglucanase, encoded by a second gene (EXG2), has been characterized as a
      heavily glycosylated, membrane bound 200 kDa glycoprotein. Finally, a third
      exoglucanase, encoded by the SSG gene, is synthesized during sporulation of
      diploids. Exoglucanases similar to those encoded by the EXG1 gene have been
      detected in other yeasts and characterized in depth in Candida albicans. The
      three polypeptides from S. cerevisiae and its counterpart from C. albicans have
      several conserved regions occupying the same relative positions. Studies on the
      function of these highly conserved enzymes are rather inconclusive.

PMID- 8298281
TI  - Biosynthesis of cell wall and septum during yeast growth.
AB  - The primary septum that forms in yeast cells at cytokinesis consists of the
      polysaccharide chitin. Three chitin synthetases (Chs1, Chs2 and Chs3) have been
      identified in Saccharomyces cerevisiae. Cloning and disruption of the respective
      genes showed that Chs3 is responsible for the formation of a chitin ring at the
      base of an emerging bud and of chitin dispersed in the cell wall, whereas Chs2
      catalyzes the synthesis of a chitin disc that completes the primary septum. Chs1
      acts as a repair enzyme, replenishing chitin lost through excessive action of a
      chitinase that facilitates cell separation by degrading part of the septum. The
      major structural polysaccharide of the yeast cell wall is beta(1->3)glucan. The
      glucan synthetase complex is bound to the plasma membrane. By differential
      extraction of the membranes with salt and detergents two solubilized fractions
      have been obtained which are required, in addition to GTP, for glucan synthesis.
      Further purification of one of these fractions led to results that indicate a
      role for other proteins in the modulation of GTP stimulation. A G-protein system
      appears to function in the regulation of beta(1->3) glucan and cell wall
      formation in vivo.

PMID- 8298282
TI  - Linkages between macromolecules in Candida albicans cell wall.
AB  - Wall mannoproteins can be divided into two major groups depending upon their
      degree of interaction with the structural network: one type interacts by non
      covalent bonds while the second group seems covalently bound to other wall
      components (intrinsic or structural mannoproteins). Cytological and biochemical
      studies have shown that mannoproteins are distributed randomly throughout cell
      wall interacting with glucan, chitin and other mannoproteins. Experimental
      results obtained using regenerating protoplasts have shown that building of the
      wall occurs in two steps: during the first one the skeleton of chitin is formed
      retaining protein molecules by non-covalent bonds. The second steps take place by
      deposition of glucan molecules that allows incorporation of mannoproteins
      probably by covalent linkages. Using two monoclonal antibodies, one of them
      reacting with a mycelial specific antigen and a second one with an epitope found
      in yeast and mycelial cells, two families of proteins are detected, that are
      secreted independently. The antigens reacting with both monoclonal antibodies are
      solubilized from the walls of each morphologic structure forming part of
      supramolecular structures.

PMID- 8298283
TI  - Determination of free and total proline and hydroxyproline in plasma and tissue
      samples by gas chromatography with flame photometric detection.
AB  - A selective and sensitive method for the determination of free and total proline
      (Pro) and 4-hydroxyproline (Hyp) by gas chromatography (GC) was developed. For
      free Pro and Hyp analysis, plasma and tissue homogenate were extracted with
      methanol. For total Pro and Hyp analysis, these samples were hydrolysed in 6 M
      HCl. After removal of primary amino compounds by the reaction with o
      phthaldialdehyde, Pro and Hyp in methanol extract and acid hydrolysate were
      converted into their N-dimethylthiophosphoryl methyl ester derivatives and then
      determined by GC with flame photometric detection using a DB-5 capillary column.
      This method was successfully applied to small samples without prior clean-up, and
      Pro and Hyp in these samples could be analysed without any influence from
      coexisting substances. Overall recoveries of Pro and Hyp added to plasma and
      tissue samples were 92-106%. The analytical results of free and total Pro and Hyp
      in human plasma and mouse tissue samples are presented.

PMID- 8298284
TI  - Metabolic fate of fenitrothion in liver, kidney and brain of rat.
AB  - The metabolic fate of fenitrothion, O,O-dimethyl-O-(3-methyl-4-nitro phenyl)
      phosphorothioate, was investigated in rat tissues during the first 24 hours
      following the intramuscular administration of the pesticide in the animal. High
      performance liquid chromatography (HPLC) of the pesticide and its metabolites
      formed in liver, kidney and brain showed the time-dependent sequential conversion
      of the pesticide into three major metabolites. These metabolites were separated
      and purified to homogeneity by HPLC and characterized by IR spectroscopy as O,O
      dimethyl-O-)3-methyl-4-aminophenyl) phosphorothioate (metabolite I), O,O-dimethyl
      phosphorothioate (metabolite II), and O,O-dimethylphosphate (metabolite III).
      These results indicated reduction of the nitro group in fenitrothion aas the
      first step, followed by the hydrolytic cleavage of the P-O-aryl bond in
      metabolite I and the oxidative desulphurylation of metabolite II. Fenitrothion
      was found to induce ultrastructural changes in liver cells especially after 12 h
      exposure nuclear membrane was completely distorted, nuclear intactness was
      totally lost and smooth endoplasmic reticulum and Golgi apparatus were abnormally
      enlarged. In 24 h, however, the regeneration of the nuclear material was
      observed.

PMID- 8298285
TI  - A sensitive and rapid HPLC-ECD method for the simultaneous analysis of
      norepinephrine, dopamine, serotonin and their primary metabolites in brain
      tissue.
AB  - This report details a very sensitive, rapid and accurate ion-pair HPLC-ECD method
      for the analysis of biogenic amines and their metabolites in brain tissue. The
      method described enables detection of picogram amounts of 3-methoxy-4-hydroxy
      phenethyleneglycol (MHPG) (37 pg), 3,4-dihydroxy phenylacetic acid (DOPAC) (18
      pg), norepinephrine (NE) (12 pg), epinephrine (E) (6 pg), 5-hydroxyindoleacetic
      acid (5-HIAA) (18 pg), 3,4-dihydroxyphenylethylamine (DA) (6 pg), 3-methoxy-4
      hydroxyphenylacetic acid (HVA) (12 pg) and 5-hydroxytryptamine (5-HT) (12 pg).
      The linearity of the method is from 18.75 ng/mL to 300 ng/mL for MHPG; 9.37 to
      150 ng/mL for DOPAC and 5-HIAA; 6.25 to 100 ng/mL for NE, HVA and 5-HT; and from
      3.12 to 100 ng/mL for E and DA. The reproducibility, expressed as coefficient of
      variance (CV%) within-run and between-run groups, was 2.25% and 19.49% for MHPG;
      3.84% and 29.84% for DOPAC; 0.89% and 8.97% for NE; 1.26% and 5.61% for E; 1.07%
      and 28.77% for 5-HIAA; 2.65% and 10.65% for DA; 5.97% and 24.38% for HVA; and
      4.44% and 9.45% for 5-HT.

PMID- 8298286
TI  - High performance liquid chromatography of tamoxifen and metabolites in plasma and
      tissues.
AB  - An isocratic reversed-phase high performance liquid chromatographic method for
      the determination of tamoxifen and its metabolites in plasma and tissues is
      described. Plasma or tissue homogenate was extracted with methanol/dimethyl
      sulphoxide (4:1 v/v). The supernatant after centrifugation was separated on a BDS
      Hypersil column with methanol/0.5 M ammonium acetate (75:25 v/v) as the mobile
      phase. The recoveries of tamoxifen added to plasma and liver tissue homogenate by
      the extraction procedure were 102 +/- 1.6 and 98 +/- 2.4% (mean +/- SD, n = 6),
      respectively. The solutes were detected at 280 nm with a detection limit of 0.25
      micrograms/mL for tamoxifen.

PMID- 8298287
TI  - Thin-layer chromatographic determination of brain catecholamines and 5
      hydroxytryptamine.
AB  - A simple and sensitive (up to nanogram level) method to determine norepinephrine,
      serotonin and dopamine in rat brain is described. The amines are acetylated and
      the derivatives are resolved by thin layer chromatography (TLC) on silica high
      performance thin layer chromatography (HPLC) plates. Quantification is achieved
      by fluorescence densitometry at 415 nm excitation wavelength.

PMID- 8298288
TI  - Studies on silica-bonded monoclonal antibody packing material for separation of
      recombinant interferon by high performance immunoaffinity chromatography.
AB  - A method for the preparation of a new packing material for high performance
      liquid chromatography by bonding an anti-interferon monoclonal antibody to the
      surface of silica gel is described. The high coupling efficiency and activity of
      the interferon-alpha A-monoclonal antibody (IFN-alpha A-McAb) column were
      obtained by activated diol-silica gel with an activating agent. After
      purification with this packing material, the specific activity of recombinant
      human interferon-alpha A rose by up to 1.03 x 10(7)IU/mg protein and the
      purification efficiency was increased by approximately 100 times.

PMID- 8298289
TI  - A Cantabrian innovation: the clinical career pathway for nurses.

PMID- 8298290
TI  - The essence of nursing: an exemplar.

PMID- 8298291
TI  - Nurses' attitudes to and knowledge of medicines.
AB  - Nurses are often required to give information about prescribed medication to
      patients. This study obtained information about the attitudes to, and knowledge
      of, prescribed medication from a group of 70 students and 24 registered nurses at
      the Otago Polytechnic. A self administered questionnaire, previously used in a
      community survey in Southampton, UK, was used for this purpose. No significant
      difference between the two groups was observed. Thirty three (35%) of all the
      responders kept their unused medicines, 19 (20%) disposed them in the household
      wastes and only 6 (6.3%) returned them to the pharmacist. About 13 (14%) admitted
      taking medication prescribed for someone else and 16 (17%) allowed others to use
      their prescribed medication. Out of the 51 responders who took a prescribed
      medicine in the past month, only 31 (61%) were aware of potential side effects.
      Although it is reassuring to know that students and registered nurses are aware
      of potential problems related to taking medication, clearly there is considerable
      room for improvement. This should include further information and appreciation of
      safe disposal methods, what to do if a dose is missed and the dangers of taking
      another person's prescribed medications.

PMID- 8298292
TI  - Nursing practice in New Zealand is reaching crisis point.

PMID- 8298293
TI  - "Measles, mumps and mud": childhood epidemics at the turn of the century.
AB  - Childhood epidemics were a commonly accepted part of life in the two decades
      around the turn of the century. Official health and education records portray,
      however, not an apathetic acceptance of epidemics but a public concern with their
      prevention and control. Education boards referred to outbreaks of measles, mumps,
      whooping-cough, scarlet fever and diphtheria in explaining poor attendance rates
      while school inspectors commented on the impact that epidemics had on schoolwork.
      District health officers closed and disinfected schools to prevent the spread of
      infection, and outside of schools nurses became actively engaged in the public
      health campaign to counteract epidemics, particularly in the remote rural
      districts. Both health and education records therefore portray the public concern
      and official actions in contending with childhood epidemics at the turn of the
      century in New Zealand.

PMID- 8298294
TI  - A glimpse of nursing in Vietnam.

PMID- 8298295
TI  - Reintroducing Evelyn Lowen. Interview by Barbara Lowen.

PMID- 8298296
TI  - Cultural safety in nursing education in Aotearoa (New Zealand).

PMID- 8298297
TI  - Polytechnic nursing students recording exemplars.

PMID- 8298298
TI  - Student exemplar.

PMID- 8298299
TI  - "Nursing: towards a positive future".

PMID- 8298300
TI  - Epithelium-free area in the thymic cortex of rats.
AB  - The histology of epithelium-free areas in the subcapsular region of the thymus
      was studied in Wistar rats. Lymphocytes in these areas were CD4/CD8 double
      positive, TCR alpha/beta positive in low intensity, and in CD5 labeling either
      negative or positive in low intensity. There was a high proliferative activity as
      assessed by bromodeoxyuridine incorporation in vivo and detected by
      immunohistochemistry. Various macrophage types were observed. They were either
      large and round to slightly dendritic, or small and dendritic. Most large cells
      were positive for MHC Class II, and labeled by the antimacrophage antibodies ED1
      and ED2. A few cells were strongly positive for Sudan black, Oil red O,
      nonspecific esterase, and acid phosphatase; they resembled the large rounded
      macrophages in the corticomedullary zone, although their MHC Class II and ED2
      staining was more intense. A few cells showed features of tangible body
      macrophages, as they contained cellular debris. Serial sections showed that
      epithelium-free areas run from the subcapsular area to deep in the cortex, and
      often border the medulla. This opens the opportunity for immature lymphocytes to
      move into the medulla and corticomedullary zone without contacting and potential
      selection with cortical stromal elements other than macrophages in the epithelium
      free areas. In this case, the epithelium-free areas may offer a separate
      intrathymic pathway for T lymphocytes.

PMID- 8298301
TI  - Phenotypic mapping of the chicken embryonic thymic microenvironment developing
      within an organ culture system.
AB  - The chicken thymic microenvironment, as it developed in an embryonic thymus organ
      culture system, was phenotypically mapped using a panel of mAb defining both
      epithelial and nonepithelial stromal cell antigens. We have previously reported
      that thymocyte proliferation and differentiation with proceed for up to 6-8 days
      in thymus organ culture, hence demonstrating the functional integrity of the
      thymic microenvironment in vitro. During this time, the stromal component
      reflected that of the normal embryo with cortical and medullary epithelial areas
      readily identifiable by both morphology and surface-antigen expression. An
      abundance of subcapsular and cortical epithelial antigens was detected in the
      cultured thymus, particularly those normally expressed by the epithelium lining
      the capsule, trabeculae, and vascular regions (type I epithelium) in the adult
      and embryonic thymus. Medullary epithelial antigens developed in organ culture,
      although were present in lower frequency than observed in the age-matched
      embryonic thymus. MHC class II expression by both epithelial and nonepithelial
      cells was maintained at high levels throughout the culture period. With
      increasing time in culture, the ratio of epithelial to nonepithelial cells
      decreased, concurrent with a decrease in thymocyte frequency and suggestive of a
      bidirectional interaction between these two cell types. Thus, a functionally
      intact thymic microenvironment appears to be maintained in embryonic thymus organ
      culture, a model that is currently being exploited to assess the role of stromal
      antigens, as defined by our mAb, in the process of thymopoiesis.

PMID- 8298302
TI  - Developmental and anatomical patterns of IL-2 gene expression in vivo in the
      murine thymus.
AB  - Interleukin-2 (IL-2) is a potent growth factor that mature T lymphocytes
      synthesize and use as a proliferation signal. Much controversy has arisen
      concerning whether it is used to drive the extensive proliferation of immature
      pre-T cells in the thymus. Immature thymocytes acquire the competence to express
      IL-2 at an early stage, but it has remained uncertain whether they are activated
      to exercise this competence in vivo. Therefore, we have used in situ
      hybridization and immunohistochemistry on serial sections obtained from fetal and
      adult thymuses of normal C57BL/6 mice and of mice bearing the scid defect to
      determine where, when, and whether IL-2 is expressed in vivo. Our results show a
      striking spatial and temporal pattern of IL-2 expression in the normal fetal
      thymus. We detected a burst of IL-2 mRNA accumulation at day 14.5 of gestation,
      which rapidly decreased by day 15. At day 15, we observed maximal IL-2 protein
      production that subsequently decreased by day 16 of gestation. Both in situ
      hybridization and immunohistochemical staining revealed an unexpectedly strict
      localization of IL-2 expressing cells to patches around the periphery of the
      fetal thymus, creating a previously unrecognized compartment of high IL-2 protein
      content. IL-2 production in the day-15 fetal thymus appeared to be unaffected by
      the scid mutation, indicating that this response is likely to be T-cell receptor
      (TcR)-independent. Several features distinguish the IL-2 induction pattern in the
      adult thymus from that in the fetal thymus. In the normal adult thymus, IL-2
      expressing cells are extremely rare (found at a frequency of 10(-7)), but they
      are reproducibly detectable as isolated cells in the outer cortex and subcapsular
      region of the thymus. Unlike the fetal thymic IL-2 producers, the IL-2 producers
      in the adult thymus are completely eliminated in mice homozygous for the scid
      mutation. This suggests that the IL-2-expressing cells in the normal adult thymus
      are of a more mature phenotype than the immature, TcR-negative cells that
      accumulate in the scid adult thymus. Thus, our work demonstrates that two
      developmentally distinct types of cell interactions induce IL-2 expression in
      vivo: one, a broadly localized interaction in day 14-15 fetal thymus that is
      unaffected by the scid mutation; the other, a rare event that occurs
      asynchronously from late fetal through adult life, but which is completely
      eliminated by the scid defect.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8298303
TI  - The glycosylation of antibody molecules: functional significance.

PMID- 8298304
TI  - Preferred conformations and dynamics of five core structures of mucin type O
      glycans determined by NMR spectroscopy and force field calculations.
AB  - Glycosyltransferases acting on O-glycans have been shown to exhibit distinct
      specificity for the carbohydrate and the peptide moiety of their substrates. As
      an approach to study the 3-dimensional interactions between enzymes and O-glycan
      substrates, we determined the preferred conformations of five oligosaccharide
      core structures of mucin type glycoproteins by NMR spectroscopy and by static and
      dynamic force field calculations. Seven oligosaccharides, representing five basic
      core structures, were investigated: Gal beta (1-3)GalNAc alpha Bzl (1, core 1),
      GlcNAc beta (1-6)[Gal beta (1-3)]GalNAc alpha Bzl (2, core 2), GlcNAc beta (1
      3)GalNAc alpha Bzl (3, core 3), GlcNAc beta (1-6)[GlcNAc beta (1-3)]GalNAc alpha
      Bzl (4, core 4), GlcNAc beta (1-6)GalNAc alpha Bzl (5, core 6), the elongated
      core 2, Gal beta (1-4)GlcNAc beta (1-6)[Gal beta (1-3)]GalNAc alpha pNp (6) and
      GalNAc alpha-Bzl (7). The dynamic behaviour of the molecules was studied by
      Metropolis Monte Carlo (MMC) simulations. Experimental coupling constants,
      chemical shift changes, and NOEs were compared with results from static energy
      minimizations and dynamic MMC simulations and show a good agreement. MMC
      simulations show that the (1-6) linkage is much more flexible than the (1-3) or
      the (1-4) linkages. The preferred conformations of the disaccharides (1) and (3)
      show only slight differences due to the additional N-acetyl group in (3). The
      conformational equilibrium of beta (1-3) glycosidic bonds of 1 and 3 was not
      affected by attaching a beta (1-6) linked GlcNAc unit to the GalNAc residue in 2
      and 4. However, experimental and theoretical data show that the beta (1-6)
      linkages of the trisaccharides 2 and 4, which carry an additional beta (1-3)
      linked glycosyl residue, change their preferred conformations when compared with
      (5). The 6-branch also shows significant interactions with the benzyl aglycon
      altering the preferred conformation of the hydroxymethyl group of the GalNAc to a
      higher proportion of the gt conformer. The (1-6) linkage of 2, 4, and 6 can have
      two different families of conformations of which the lower energy state is
      populated only to about 20% of the time whereas the other state with a relative
      enthalpy of approximately 4 kcal mol-1 is populated to 80%. This fact
      demonstrates that the two conformational states have different entropy contents.
      Entropy is implicitly included in MMC simulations but cannot be derived from
      energy minimizations.

PMID- 8298306
TI  - Lysosomal sulfate efflux following glycosaminoglycan degradation: measurements in
      enzyme-supplemented Maroteaux-Lamy syndrome fibroblasts and isolated lysosomes.
AB  - Studies using lysosomal membrane vesicles have suggested that efflux of the
      sulfate that results from lysosomal glycosaminoglycan degradation is carrier
      mediated. In this study, glycosaminoglycan degradation and sulfate efflux were
      examined using cultured skin fibroblasts and lysosomes deficient in the lysosomal
      enzyme N-acetylgalactosamine-4-sulfatase. Such fibroblasts store dermatan sulfate
      lysosomally, which could be labelled biosynthetically with Na2(35)SO4. The
      addition of recombinant N-acetylgalactosamine-4-sulfatase to the media of 35S
      labelled fibroblasts degraded up to 82% of the stored dermatan [35S] sulfate over
      a subsequent 96 h chase and released inorganic [35S] sulfate into the medium. In
      the presence of 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid
      (SITS), sulfate was reused to a minor extent in newly synthesized proteoglycan.
      Isolated granules from recombinant enzyme supplemented fibroblasts degraded
      stored dermatan [35S]sulfate to sulfate which was rapidly released into the
      medium at a rate that was reduced by the extra-lysosomal presence of the
      lysosomal sulfate transport inhibitors SITS, Na2SO4 and Na2MoO4. SITS also
      inhibited dermatan sulfate turnover, although it had no effect on the action of
      purified recombinant enzyme in vitro. These data imply that sulfate clearance
      occurred concomitantly with dermatan sulfate turnover in the lysosome even at
      high substrate loading, and that lysosome-derived sulfate, while available, is
      reutilized minimally in synthetic pathways.

PMID- 8298307
TI  - [Ambulatory surgery and endoscopic surgery].

PMID- 8298305
TI  - Processing O-glycan core 1, Gal beta 1-3GalNAc alpha-R. Specificities of core 2,
      UDP-GlcNAc: Gal beta 1-3 GalNAc-R(GlcNAc to GalNAc) beta 6-N
      acetylglucosaminyltransferase and CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3
      sialyltransferase.
AB  - To elucidate control mechanisms of O-glycan biosynthesis in leukemia and to
      develop biosynthetic inhibitors we have characterized core 2 UDP-GlcNAc:Gal beta
      1-3GalNAc-R(GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase (EC
      2.4.1.102; core 2 beta 6-GlcNAc-T) and CMP-sialic acid: Gal beta 1-3GalNAc-R
      alpha 3-sialyltransferase (EC 2.4.99.4; alpha 3-SA-T), two enzymes that are
      significantly increased in patients with chronic myelogenous leukemia (CML) and
      acute myeloid leukemia (AML). We observed distinct tissue-specific kinetic
      differences for the core 2 beta 6-GlcNAc-T activity; core 2 beta 6-GlcNAc-T from
      mucin secreting tissue (named core 2 beta 6-GlcNAc-T M) is accompanied by
      activities that synthesize core 4 [GlcNAc beta 1-6(GlcNAc beta 1-3)GalNAc-R] and
      blood group I [GlcNAc beta 1-6(GlcNAc beta 1-3)Gal beta-R] branches; core 2 beta
      6-GlcNAc-T in leukemic cells (named core 2 beta-GlcNAc-T L) is not accompanied by
      these two activities and has a more restricted specificity. Core 2 beta 6-GlcNAc
      T M and L both have an absolute requirement for the 4- and 6-hydroxyls of N
      acetylgalactosamine and the 6-hydroxyl of galactose of the Gal beta 1-3GalNAc
      alpha-benzyl substrate but the recognition of other substituents of the sugar
      rings varies, depending on the tissue. alpha 3-sialyltransferase from human
      placenta and from AML cells also showed distinct specificity differences,
      although the enzymes from both tissues have an absolute requirement for the 3
      hydroxyl of the galactose residue of Gal beta 1-3GalNAc alpha-Bn. Gal beta 1-3(6
      deoxy)GalNAc alpha-Bn and 3-deoxy-Gal beta 1-3GalNAc alpha-Bn competitively
      inhibited core 2 beta 6-GlcNAc-T and alpha 3-sialyltransferase activities,
      respectively.

PMID- 8298308
TI  - [Surgical gynecology today and tomorrow. Leading presentation of the 13th
      Academic Congress of German-Speaking University Faculty in Gynecology and
      Obstetrics, Hannover, 16th-19th May 1993: 1: Oncology and urologic gynecology].
AB  - It is shown how in gynaecologic oncology, proceeding from former standardized
      techniques, an individualized multimodal therapeutic concept has been developed.
      New aspects are introduced concerning diagnosis and treatment in the field of
      operative urogynaecology. The world-wide problem of performing poorly indicated
      hysterectomies is also addressed. Dynamic developments in the field of out
      patient surgery will become an increasing challenge in the near future,
      influencing obstetrics and gynaecology to an extent that cannot at present be
      foreseen for the middle and long range. The forced evolution of conventional and
      laser-assisted laparoscopic surgery resulted in a nowadays broad spectrum of
      laparoscopically practicable surgical interventions, which made, even if still
      questioned by some experts, the vaginally assisted laparoscopic hysterectomy
      possible.

PMID- 8298309
TI  - [Treatment of vulvar cancer].
AB  - 125 patients with carcinoma of the vulva were evaluated with respect to corrected
      5-year survival rates. In our study we try to answer two questions in the
      therapeutic management of vulval carcinoma: (1) Is organ-preserving surgery in
      stage I tumors adequate? (2) How important is the radiation therapy in the
      general treatment concept in more advanced stages of the disease? Our study shows
      that organ preservation seems to be possible in stage I disease, if resection of
      the tumor is complete with a margin of normal tissue. If inguinal lymph nodes are
      involved or the primary tumor is bulky, the best results are obtained with a
      combination of radical surgery and locoregional radiation therapy. Radiation
      therapy alone has a good effect during the early stage of the vulval cancer.

PMID- 8298310
TI  - [Characteristics of the menstrual cycle in relation to sex-typical distribution
      of fatty tissue].
AB  - The association between duration as well as regularity of the menstrual cycle and
      the sex type specific distribution of the subcutaneous fat tissue has been
      investigated in 327 patients. It turned out that the so-called 'gynecoid'
      subcutaneous fat distribution was associated with shorter and more regular
      menstrual cycles. A marked relationship between the sex type specific fat
      distribution and the bleeding duration could not found.

PMID- 8298311
TI  - [Is determination of the "free androgen index" for hormone screening in
      polycystic ovaries of value?].
AB  - In 82 females with hyperandrogenism and polycystic ovaries, the sensitivity and
      diagnostic accuracy of the free-androgen index (FAI) were compared with those of
      testosterone (T), free testosterone (fT), androstenedione (A), LH and the LH/FSH
      ratio. Normal ranges for each parameter were derived as 95th percentile in 53
      healthy controls of similar age. T, fT, A, FAI, LH and LH/FSH were significantly
      (p < 0.001) higher in patients than controls. The sensitivity and diagnostic
      accuracy of the FAI (0.46 and 0.64) were lower than those of T (0.67 and 0.78)
      and A (0.56 and 0.73) and similar to those of fT and LH/FSH. The overall variance
      of the FAI was highest among all parameters. The FAI was significantly (p = 0.05)
      elevated in a subgroup with obesity (n = 34), whereas T and fT did not differ in
      obese and nonobese subjects with polycystic-ovary syndrome. We cannot recommend
      the routine measurement of the FAI in the rational laboratory evaluation of
      female hyperandrogenism for the following reasons. (1) The adequate normal range
      for the FAI (< 8.7) is substantially higher than previously thought in normal
      individuals, which has serious consequences for the accuracy of the test. (2) The
      values of the FAI showed the widest overlap with controls. (3) The significant
      positive correlation between FAI and fT allows the prediction of the FAI from the
      measurement of fT, rendering the determination of a second parameter for the free
      bioactive T unnecessary. (4) The FAI as well as sex-hormone-binding globulin are
      influenced by body weight, whereas T and fT are markers for hyperandrogenism
      independent of obesity.

PMID- 8298312
TI  - [Evaluation of tumor extension in invasive cancer of the uterine cervix.
      Diagnostic evaluation of cervix cancer].
AB  - Cancer of the uterine cervix accounts for approximately 30% of deaths from
      malignancies in gynecology and this rate has remained unchanged for more than 40
      years. The most important prognostic factor is the extent of the disease at the
      beginning of treatment. There is, however, a discrepancy of some 50% between
      clinical and postoperative staging. The aim of this study was to evaluate
      different diagnostic investigations leading to the preoperative classification
      (FIGO) of 261 patients with cervical cancer. Data of presurgical clinical and
      radiological examinations were compared with postoperative histopathological
      findings. Rectovaginal palpation and computerized tomography (CAT) both showed a
      positive predictive value of 60%. The performance of CAT and lymphography in the
      diagnosis of lymph node metastasis was poor with positive predictive values of
      36.3 and 20%, respectively. In the absence of parametrial infiltration on
      palpation, cystoscopy and rectoscopy are superfluous since they are always
      normal. Urography, because of the possibility to show the topographic anatomy of
      the urinary tract, was justified in all cases. The value of surgical staging and
      more recent techniques such as sonography and magnetic resonance is discussed.

PMID- 8298313
TI  - [The Vienna obstetric forceps].
AB  - The 'Wiener Schulzange' was first used by the Second Medical School in Vienna,
      the beginning of which must be assumed around the year 1848, and goes back to Sir
      James Young Simpson in Edinburgh and Carl Braun Ritter von Fernwald in Vienna.
      The forceps was produced in Vienna by Josef Leiter, who was well known for making
      surgical instruments. Names like Francis Henry Ramsbotham, John Aitken, David
      Evans, Dietrich Wilhelm Heinrich Busch and Hermann Josef Brunninghausen are
      connected with the development of the Viennese forceps; its English lock goes
      back to William Smellie. The arms of the Viennese forceps, which, being a forceps
      of the crossed type, forms a two-armed lever, were originally forged from one
      piece each and brazed with the separately manufactured handles.

PMID- 8298314
TI  - [Recommendations of the Urogynecology Study Group on urogynecologic diagnosis and
      therapy].

PMID- 8298315
TI  - [Obstetrics--a mirror of society].

PMID- 8298316
TI  - [Systemic therapy of OAT (oligoasthenoteratozoospermia) syndrome with
      pentoxifylline].

PMID- 8298317
TI  - [Successful in vitro fertilization in cattle with transmigrated semen without
      heparin, hypotaurine and adrenaline supplements].

PMID- 8298319
TI  - [Report of the "5th Congress of the Perinatal Doppler Society". New York, 29
      August to 2 September 1992].

PMID- 8298318
TI  - [Testicular azoospermia].

PMID- 8298320
TI  - The paleopathology of the cardiovascular system.
AB  - Paleopathology, the study of disease in ancient remains, adds the dimension of
      time to our study of health and disease. The oldest preserved heart is from a
      mummified rabbit of the Pleistocene epoch, over 20,000 years old. Cardiovascular
      disease has been identified in human mummies from Alaska and Egypt, covering a
      time span ranging from approximately 3,000 to 300 years ago. An experimental
      study suggests that the potential exists for identifying a wide range of
      cardiovascular pathologic conditions in mummified remains. The antiquity and
      ubiquity of arteriosclerotic heart disease is considered in terms of
      pathogenesis.

PMID- 8298321
TI  - Use of the activated clotting time in anticoagulation monitoring of intravascular
      procedures.
AB  - The activated clotting time first came into clinical use in the mid-1970s to
      guide the administration and reversal of heparin during cardiopulmonary bypass
      procedures. The explosive growth of cardiopulmonary bypass led to the development
      of automated techniques for measuring activated clotting times. Recent advances
      in the field of interventional cardiology have emphasized the importance of the
      coagulation cascade and the need for the prevention of thrombosis with
      anticoagulant drugs. The activated clotting time has emerged as an important
      means of monitoring and guiding heparin therapy during invasive intravascular
      procedures. This review focuses on the following topics: 1) the development of
      anticoagulation monitoring techniques; 2) current alternatives in bedside
      anticoagulation monitoring; and 3) the clinical application of activated clotting
      times outside surgery. Until prospective studies can establish appropriate
      "target" activated-clotting-time values for interventional procedures, procedural
      anticoagulation must be guided empirically. Nevertheless, the activated clotting
      time is extremely useful in the catheterization laboratory, for monitoring
      heparin therapy and the adequacy of anticoagulation.

PMID- 8298322
TI  - Clinical experience with the transvenous Medtronic Pacer Cardioverter
      Defibrillator (PCD) System.
AB  - We review our experience with the transvenous Medtronic Pacer Cardioverter
      Defibrillator System (Model 7217B), a multifunction implantable pacer
      defibrillator combined with a transvenous lead system (Transvene). From April
      1991 to October 1992, we implanted this device in 19 consecutive patients (11 men
      and 8 women; average age, 56.5 years). Nine patients (47.4%), 5 with coronary
      artery disease and 4 with dilated cardiomyopathy, had an ejection fraction of <
      30%. The average operative time was 129 minutes. In 18 patients (94.7%), the
      transvenous lead system provided effective sensing, pacing, and defibrillation
      during intraoperative testing. In each of these cases, the defibrillation
      threshold was less than 18 J. In 1 patient (5.3%), it was necessary to switch to
      epicardial leads, which were implanted through a left thoracotomy. All patients
      were extubated in the recovery room. The average hospital stay was 8 days. There
      was no early mortality or morbidity. During a maximum follow-up period of 17
      months (mean, 9.2 months), no sudden death occurred. The implantable system
      terminated 245 ventricular tachycardia episodes in 14 patients (73.7%) and 82
      ventricular fibrillation episodes in 13 patients (68.4%). Two hundred eleven
      (86.1%) of the ventricular tachycardia episodes were resolved by antitachycardia
      pacing alone. In 2 patients (10.5%), the caval electrode became dislocated;
      repositioning of the electrode was followed by repeat defibrillation threshold
      evaluation. Our experience shows that the transvenous Medtronic Pacer
      Cardioverter Defibrillator System provides safe, effective treatment of
      ventricular tachyarrhythmias. Because the perioperative mortality and morbidity
      are extremely low, use of this device may be particularly beneficial in patients
      with a high operative risk. Moreover, the lower number of unpleasant therapeutic
      shocks should increase patient a acceptance of the device.

PMID- 8298323
TI  - Ross operation using a bovine bioprosthetic valve with autologous pericardial
      conduit in the pulmonary position.
AB  - Between 1 February 1992 and 1 March 1993, we performed Ross's aortic replacement
      in 7 men and 4 women with rheumatic heart disease. The patients' ages ranged from
      22 to 60 years (mean, 41 years). All 11 patients had aortic valve disease; 2 also
      had mitral valve disease. In all patients, the right ventricular outflow tract
      was reconstructed using an autologous pericardial conduit containing a bovine
      cardiac valve bioprosthesis manufactured at our institution. The 2 patients who
      had mitral valve disease underwent a concomitant mitral valvuloplasty. In 1
      patient, minimal aortic regurgitation was documented by means of transesophageal
      echocardiography immediately after the cessation of cardiopulmonary bypass, but
      no hemodynamic compromise was noted. In another patient, mediastinal exploration
      was required for bleeding, 3.5 hours postoperatively. The follow-up period ranged
      from 6 to 16 months (mean, 11.3 months). Results were assessed by means of
      clinical and transesophageal echocardiographic studies. No infection or technical
      failure was encountered. No patient died. All patients remain asymptomatic, and
      follow-up echocardiography has revealed no transaortic or transpulmonary
      gradient. The Ross operation was chosen for this group of patients because it
      avoids the use of mechanical valves and subsequent anticoagulant therapy. Most of
      our patients have a low income and a history of noncompliance with the strict
      postoperative drug regimen. Although the short-term results have been excellent
      with the Ross operation and our combination bioprosthesis, long-term evaluation
      is needed.

PMID- 8298324
TI  - Peripheral organ perfusion augmentation during left ventricular failure. A
      controlled bovine comparison between the intraaortic balloon pump and the
      Hemopump.
AB  - Despite the use of inotropic therapy and the intraaortic balloon pump (IABP),
      inadequate peripheral organ perfusion and subsequent multiorgan failure from left
      ventricular dysfunction is a major cause of death following cardiac surgery. To
      compare the end-organ perfusion provided by the IABP with that of the recently
      developed Hemopump Cardiac Assist System, blood flow from visceral organs was
      measured by ultrasonic flow probes during separate periods of support with each
      of these pumps. Ten calves underwent coronary artery ligations with beta-receptor
      blockade; hemodynamic parameters were recorded before the induction of failure,
      during unsupported cardiac failure, and during Hemopump and IABP support.
      Improvement in mean cardiac output, mixed venous oxygen saturation, and pulmonary
      artery wedge pressure was significantly greater (p < 0.05) during Hemopump
      support than during IABP support. Renal artery flow was significantly greater
      during Hemopump support (276 +/- 74.2 cc/min) than during IABP support (164 +/-
      79.6 cc/min). Hepatic artery flow was significantly greater during Hemopump
      support (34.7 +/- 25.7 cc/min) than during IABP support (24.4 +/- 18.9 cc/min),
      and portal vein flow was significantly greater during Hemopump support (1588 +/-
      315 cc/min) than IABP support (1259 +/- 310 cc/min). There were no significant
      differences, however, between carotid artery flow during Hemopump support (292 +/
      171 cc/min) and that during IABP support (317 +/- 204 cc/min). We conclude that
      renal, hepatic, and mesenteric perfusion provided by the nonpulsatile Hemopump is
      superior to that of the IABP in this bovine model of left ventricular failure.
      Therefore, the Hemopump may be more effective in preventing multiorgan failure
      during recovery of ventricular function.

PMID- 8298325
TI  - A suggested technique for "orthotopic" heart transplantation in a patient with
      situs inversus.
AB  - We describe a technique for "orthotopic" heart transplantation in a patient with
      situs inversus. The left atrial, aortic, and pulmonary artery anastomoses were
      performed directly, in the usual manner. The recipient's right atrium was
      converted into a tunnel, and the donor's right atrium was left intact.
      Anastomoses were therefore required between the 2 inferior venae cavae (by direct
      end-to-end anastomosis) and the 2 superior venae cavae (necessitating the
      insertion of a Dacron-graft). We suggest that even simpler techniques, perhaps
      not requiring the use of an artificial vascular prosthesis, are possible.

PMID- 8298326
TI  - Anterior translocation of the pulmonary confluence in the surgical treatment of
      truncus arteriosus.
AB  - A surgical technique is described for correction of truncus arteriosus type II,
      in which the confluence of the pulmonary arteries is translocated anteriorly to
      the divided truncal root. In this technique, the truncal root is reconstructed,
      and the ventricular septal defect is closed through a right ventriculotomy. The
      outflow tract of the right ventricle is reconstructed by using a cryopreserved
      aortic homograft, with the pulmonary artery confluence lying anteriorly to the
      aorta. This positioning may facilitate future reoperation in patients with this
      anomaly by obviating dissection around the truncal artery.

PMID- 8298327
TI  - Vena cava bypass with stented polytetrafluoroethylene bifurcated grafts. A report
      of 2 cases.
AB  - Severe stenosis or occlusion of either the superior or the inferior vena cava
      requires surgical bypass grafting in a selected group of patients. When the
      obstruction extends into the major tributaries, a bifurcated graft becomes
      necessary. We present the cases of 2 surgically treated patients, each of whom
      received a stented polytetrafluoroethylene bifurcated graft constructed at the
      time of the operation. Symptoms disappeared post-operatively in 1 patient and
      abated in the other. Both grafts became occluded within 1 year; however, that was
      sufficient time for collateral venous circulation to develop, enabling both
      patients to respond well to conservative therapy. We conclude that stented
      polytetrafluoroethylene bifurcated grafts may be suitable for selected patients
      as a bridge until collateral veins can form. The development of more compliant
      venous grafts may provide even more favorable results.

PMID- 8298328
TI  - Papillary fibroelastoma. A right atrial presentation.
AB  - Papillary fibroelastoma is a rare cardiac tumor arising most frequently from
      valvular endocardium. These tumors are clinically important because of their
      tendency to embolize. Emphasis is therefore placed on early detection and
      surgical excision. We describe a case of a papillary fibroelastoma arising from
      the right atrium. To our knowledge, only 2 such cases have been reported in the
      English literature. Our case illustrates the discovery of a rare, but potentially
      fatal cardiac tumor, successfully removed by surgery.

PMID- 8298329
TI  - Cardiac metastasis of rectal adenocarcinoma. Surgical treatment.
AB  - The authors report a case of cardiac metastasis of a rectal adenocarcinoma that
      infiltrated the right ventricle and partially obstructed its outflow tract.
      Surgical treatment was performed because of syncopal attacks. The differential
      diagnosis between organized thrombi and intracardiac tumor is considered.

PMID- 8298330
TI  - Progressive visual deterioration leading to blindness after pediatric heart
      transplantation.
AB  - We present the case of a 10-year-old girl who developed visual loss progressing
      to blindness after orthotopic heart transplantation and an immunosuppressive
      regimen of cyclosporine, azathioprine, and prednisone. Headaches and visual
      deterioration began 2 months after transplantation, and a diagnosis of
      pseudotumor cerebri was made. The patient's visual loss continued despite
      aggressive medical and surgical therapy, which included bilateral optic nerve
      sheath fenestration. To our knowledge, permanent visual loss as a late sequela
      following pediatric heart transplantation and immunosuppressive therapy has not
      been reported previously in the English literature. Although the cause of visual
      loss after transplantation in our patient is poorly understood, we conclude that
      permanent visual loss, although rare, should be considered as a possible late
      neurologic sequela after pediatric heart transplantation.

PMID- 8298331
TI  - Congenital circumflex coronary artery fistula with drainage into the left
      ventricle.
AB  - Congenital coronary fistula is a rare heart defect, which consists of a
      communication between a coronary artery and a cardiac chamber of coronary vessel.
      Most such fistulae drain into a right heart chamber or into the pulmonary artery.
      Congenital left coronary artery-left ventricle fistula is even more uncommon. In
      a search of the literature, we were able to find only 15 other cases of
      congenital left coronary artery-left ventricle fistula. We describe here the
      clinical picture of a patient with left circumflex coronary artery draining into
      the left ventricle, and the successful surgical repair of the lesion. As far as
      we know, such a case has never before been reported in detail.

PMID- 8298332
TI  - Aortic valve replacement through right thoracotomy.
AB  - There has never, to our knowledge, been a report of aortic valve replacement via
      a right thoracotomy. However, we recently used this approach in 2 young women
      with severe aortic stenosis. Exposure of the aortic valve was excellent, and we
      encountered neither technical difficulties nor sequelae related to the right
      thoracotomy. We believe that right thoracotomy provides adequate access for safe
      aortic valve replacement and yields cosmetically more appealing results than does
      median sternotomy.

PMID- 8298333
TI  - Pulmonary banding complicated by low origin of right pulmonary artery.

PMID- 8298334
TI  - Mary Hale: serving her community. Interview by Cynthia Q Barger.

PMID- 8298335
TI  - Advice regarding deposition testimony.

PMID- 8298336
TI  - Counteracting benzodiazepine sedation with flumazenil.

PMID- 8298337
TI  - Overview of substance abuse: implications for the primary care nurse
      practitioner.
AB  - NPs in primary care can expect a significant percent of their patient population
      to have a substance abuse disorder. This article provides the practitioner with
      foundational information on the epidemiology and neurophysiology of substance
      abuse, models and theories of addiction, and the physical and psychological
      effects of commonly abused substances. The commonly abused legal substances,
      nicotine and alcohol, are highlighted.

PMID- 8298338
TI  - Assessment and screening for substance abuse: guidelines for the primary care
      nurse practitioner.
AB  - In ambulatory care settings, NPs can expect to encounter numerous patients who
      have had or currently have an alcohol and/or other drug problem. In addition, a
      large number of patients are estimated to have an undetected or undiagnosed
      problem. This article presents guidelines for the assessment and screening of
      patients abusing alcohol and other drugs. History-taking, screening instruments,
      physical examination, and commonly used biological markers/laboratory tests are
      described. Brief intervention techniques and referral resources are also
      discussed.

PMID- 8298339
TI  - Adolescent substance abuse: prevalence, assessment, prevention, and treatment.
AB  - Substance abuse continues to be a major problem in the preadolescent and
      adolescent age groups. Although some progress appears to have occurred in recent
      years, prevalence of alcohol and other drugs requires constant vigilance. This
      article reports current statistics of alcohol and drug use in the adolescent
      population. The NP's role as a health care provider for adolescents relative to
      screening, assessment, prevention, treatment, and referral for substance abuse is
      emphasized.

PMID- 8298340
TI  - Perinatal substance abuse: assessment and management of the pregnant woman and
      her children.
AB  - The use and abuse of alcohol and other drugs by women during the childbearing
      years continues to be an area of concern. Knowledge of the effects of drugs on
      the developing fetus and the child postnatally is essential for the NP. This
      report presents information on the assessment and screening of the pregnant woman
      who abuses substances. Interventions for mothers and children affected by
      perinatal substance abuse are also offered.

PMID- 8298341
TI  - Program for women and infants exposed to drugs: a legal alternative.
AB  - The Drug Identification, Screening, and Counseling Program is a system of care
      that uses the NP to implement a balanced perinatal program in both primary care
      and community based settings to meet the needs of mothers and babies exposed to
      drugs.

PMID- 8298342
TI  - Substance abuse among the elderly.
AB  - Substance abuse in the elderly is often missed by primary care providers. The
      signs, symptoms, and behaviors of older individuals with alcohol and other drug
      problems are frequently different from those noted in younger populations. This
      article reviews the prevalence of substance abuse among the elderly,
      characteristics of the elderly abuser, physiological effects and clinical
      manifestations, and primary, secondary, and tertiary prevention with the elderly
      abuser.

PMID- 8298343
TI  - Ischaemic preconditioning.

PMID- 8298344
TI  - Risk of lymphoma in patients with dermatitis herpetiformis.
AB  - OBJECTIVE: To provide accurate estimates of the risk of lymphoma in patients with
      dermatitis herpetiformis. DESIGN: Comparison of observed and expected incidence
      of cancer in patients with dermatitis herpetiformis. SUBJECTS: 976 patients aged
      4 to 97 years with no clinical signs of coeliac disease who were admitted to
      hospital between 1963 and 1983. SETTING: Data from Swedish Cancer Registry. MAIN
      OUTCOME MEASURES: Incidence and type of cancer. RESULTS: 106 cancers were
      diagnosed in 94 patients. The relative risk was 1.4 (95% confidence interval 1.1
      to 1.7) in male patients and 1.2 (0.8 to 1.7) in female patients. When the
      individual cancer sites were analysed a significant risk was found only for
      malignant, non-Hodgkin's lymphoma in male patients, with a relative risk of 5.4
      (2.2 to 11.1). CONCLUSIONS: The risk of lymphoma is greater in male patients with
      dermatitis herpetiformis, and this calls for increased surveillance in these
      patients.

PMID- 8298345
TI  - Prediction of hypoxaemia at high altitude in children with cystic fibrosis.
AB  - OBJECTIVE: To assess the usefulness of a hypoxic challenge in a laboratory at sea
      level in predicting acute desaturation at altitude in children with lung disease.
      DESIGN: Comparison of responses to hypoxic challenge in different settings.
      SUBJECTS: 22 children (12 boys) aged 11 to 16 years with cystic fibrosis in whom
      the mean forced expiratory volume in one second was 64% (range 24-100%). SETTING:
      Lung function laboratory, the Alps, and aboard commercial jet aircraft. MAIN
      OUTCOME MEASURES: Spirometric lung function at sea level and finger probe
      oximetry with air and 15% oxygen. Oximetry during high altitude flight and on a
      mountain at altitude of 1800 m. RESULTS: Significant desaturation (range 0 to
      12%) occurred with all hypoxic challenges (P < 0.002). The best predictor of
      hypoxic response from a single reading was the laboratory test (r2 = 76% for
      flight and r2 = 47% for mountain altitude), but the mean errors of prediction
      were not clinically significantly different. In six children who showed the
      greatest desaturation the laboratory test overestimated desaturation, but other
      predictors underestimated desaturation in three by up to 5%. CONCLUSIONS: The
      laboratory hypoxic challenge directly predicted the worst case of desaturation
      during flight and at equivalent high altitude. Spirometry and baseline oxygen
      saturations may underestimate individual hypoxic response. The test may have
      wider applications to other patients with stable chronic lung diseases,
      particularly in determining who needs supplementary oxygen during air travel and
      who should be advised against holidays at high altitude.

PMID- 8298346
TI  - Dyspnoea, asthma, and bronchospasm in relation to treatment with angiotensin
      converting enzyme inhibitors.
AB  - OBJECTIVE: To evaluate the occurrence of asthma and dyspnoea precipitated or
      worsened by angiotensin converting enzyme inhibitors. DESIGN: Summary of reports
      of adverse respiratory reaction in relation to treatment with angiotensin
      converting enzyme inhibitors that were submitted to Swedish Adverse Drug
      Reactions Advisory Committee and to World Health Organisation's international
      drug information system until 1992. Sales of angiotensin converting enzyme
      inhibitors in Sweden were also summarised. SUBJECTS: Patients receiving
      angiotensin converting enzyme inhibitors who reported adverse respiratory
      reactions. MAIN OUTCOME MEASURES: Clinical characteristics of adverse reactions
      of asthma, bronchospasm, and dyspnoea. RESULTS: In Sweden 424 adverse respiratory
      reactions were reported, of which most (374) were coughing. However, 36 patients
      had adverse drug reactions diagnosed as asthma, bronchospasm, or dyspnoea. In 33
      of these cases the indication for treatment with angiotensin converting enzyme
      inhibitors was hypertension, in only three heart failure. The respiratory
      symptoms occurred in about half of the patients within the first two weeks of
      treatment, and about one third needed hospitalisation or drug treatment. Dyspnoea
      symptoms occurred in conjunction with other symptoms from the airways or skin in
      23 out of the 36 cases. In the WHO database there were 318 reports of asthma or
      bronchospasm, 516 reports of dyspnoea, and 7260 reports of cough in relation to
      11 different angiotensin converting enzyme inhibitors. CONCLUSION: Symptoms of
      airway obstruction in relation to treatment with angiotensin converting enzyme
      inhibitors seem to be a rare but potentially serious reaction generally occurring
      within the first few weeks of treatment.

PMID- 8298347
TI  - GP facilitators and HIV infection.

PMID- 8298349
TI  - Fundholding: from solution to problem.

PMID- 8298348
TI  - Estimating numbers of homeless and homeless mentally ill people in north east
      Westminster by using capture-recapture analysis.
AB  - OBJECTIVES: To use routinely collected data to provide a reliable estimate of the
      size and psychiatric morbidity of the homeless population of a given geographical
      area by using capture-recapture analysis. DESIGN: A multiple sample, log-linear
      capture-recapture method was applied to a defined area of central London during 6
      months. The method calculates the total homeless population from the sum of the
      population actually observed and an estimate of the unobserved population. Data
      were collected from local agencies used by homeless people. SUBJECTS: Homeless
      people in north east Westminster residing in bed and breakfast accommodation and
      hotels or sleeping rough who had contacted statutory or voluntary agencies in the
      area. RESULTS: 2150 contacts by 1640 homeless people were recorded. The estimated
      unobserved population was 3293, giving a total homeless population for the period
      of around 5000 (SD 1250). Mental health problems were significantly less
      prominent in the unobserved compared with the observed population (23% (754) v
      40% (627), P < 0.0001). For both groups the prevalence varied greatly with age
      and sex. CONCLUSIONS: Capture-recapture techniques can overcome problems of
      ascertainment in estimating populations of homeless and homeless mentally ill
      people. Prevalences of mental illness derived from surveys that do not correct
      for ascertainment are likely to be falsely inflated while at the same time
      underestimating the total size of the homeless mentally ill population.
      Population estimates derived from capture-recapture techniques may usefully
      provide a good basis for including homeless populations in capitation
      calculations for allocating funds within health services.

PMID- 8298350
TI  - Lifeline Wales: experience with a computerised kidney donor registry.

PMID- 8298351
TI  - Use of a telephone advice line in an accident and emergency department.

PMID- 8298352
TI  - Morale in general practice: is change the problem or the solution.
AB  - Despite the pervading gloom about morale in general practice it can still offer a
      rewarding career. This article, which is the first in a series examining ways to
      improve general practitioners' job satisfaction, weighs the evidence for low
      morale in the profession and examines the factors that cause most
      dissatisfaction. The main causes of discontent seem to be increased paperwork and
      out of hours work, and many blame the 1990 contract for their problems.
      Dissatisfaction was growing before the contract was introduced, however, and some
      doctors believe that it has had positive effects. Further change seems inevitable
      if general practice is to offer a stimulating career for life.

PMID- 8298353
TI  - Failure to thrive.

PMID- 8298354
TI  - Conflict of interest and the BMJ.

PMID- 8298355
TI  - ABC of emergency radiology. Maxillofacial radiographs.

PMID- 8298356
TI  - Assessing the human condition: capture-recapture techniques.

PMID- 8298357
TI  - Arthroscopy.
AB  - Arthroscopy has reduced the morbidity and period of hospitalisation associated
      with orthopaedic surgery and has increased the range of procedures that may be
      performed. From early operations on the knee it has expanded to include
      procedures for the shoulder, elbow, wrist, hip, ankle, and foot. For some joints
      the indications for surgery are clear, for others the clinical advantages are
      still being assessed. This expansion has also led to the recognition of
      complications, though the incidence is low. Specialist instrumentation has
      allowed a wide variety of operations previously needing open surgery to be
      carried out arthroscopically. The repertoire of arthroscopic procedures will
      undoubtedly continue to expand, and controlled studies are required to validate
      their efficacy, particularly in the management of degenerative joint diseases.

PMID- 8298358
TI  - Drug treatment of hypercholesterolaemia. Determine cardiac risk.

PMID- 8298359
TI  - Drug treatment of hypercholesterolaemia. Establish diagnosis before treatment.

PMID- 8298360
TI  - Respiratory viruses and asthma. Importance of infection underestimated.

PMID- 8298361
TI  - Methicillin resistant staphylococcal infection. Clinical importance remains
      unevaluated.

PMID- 8298362
TI  - Methicillin resistant staphylococcal infection. Infection spreads between
      hospitals.

PMID- 8298363
TI  - Methicillin resistant staphylococcal infection. Nursing homes act as reservoir.

PMID- 8298364
TI  - Managing the third stage of labour. Nausea is a fair price for preventing
      haemorrhage.

PMID- 8298365
TI  - Managing the third stage of labour. Oxytocin more stable in tropical climates.

PMID- 8298366
TI  - Managing the third stage of labour. Reduction in haemorrhage is a major
      advantage.

PMID- 8298367
TI  - The Gardner hypothesis. Cancer not linked to radiation or chemicals.

PMID- 8298368
TI  - The Gardner hypothesis. Found wanting.

PMID- 8298369
TI  - The Gardner hypothesis. Old infective theory discredited.

PMID- 8298370
TI  - Human rights in Israeli, occupied territories.

PMID- 8298371
TI  - Tuberculous pericarditis.

PMID- 8298372
TI  - Dietary nicotine. Won't mislead on passive smoking...

PMID- 8298373
TI  - Care of mentally ill people in the community.

PMID- 8298374
TI  - Dietary nicotine. ...unless subjects eat 90 kg tomatoes a day.

PMID- 8298375
TI  - Violence at work.

PMID- 8298376
TI  - Academic base for general practice.

PMID- 8298377
TI  - Funding family planning.

PMID- 8298379
TI  - Renal disease and use of topical non-steroidal anti-inflammatory drugs.

PMID- 8298378
TI  - Indications for operation in suspected appendicitis and incidence of perforation.
AB  - OBJECTIVE: To clarify poorly understood epidemiological features of appendicitis.
      DESIGN: Retrospective study of consecutive cases from a defined population and
      analysis of data from published studies. SETTING: County of Jonkoping, Sweden.
      3029 patients who underwent operation in 1984-9 and 4717 patients from the county
      town who underwent operation in 1970-89, all for suspected appendicitis, plus
      48,426 cases from six reported studies. MAIN OUTCOME MEASURES: Incidences
      specific for age and sex and temporal trends of perforating and non-perforating
      appendicitis and removal of a normal appendix. Associations between diagnostic
      accuracy, rate of perforation, and incidences of removal of a normal appendix and
      of perforating and non-perforating appendicitis. RESULTS: The incidence of
      appendicitis was 116/100,000 inhabitants. Appendicitis was more common in male
      patients. The incidence of perforating appendicitis was independent of age,
      stable over time, and uninfluenced by the rate of laparotomy, whereas the
      incidence of non-perforating appendicitis was age dependent, decreasing over
      time, and related to the diagnostic accuracy and rate of removal of a normal
      appendix. CONCLUSIONS: Perforating and non-perforating appendicitis seem to be
      separate entities, and appendicitis that resolves spontaneously is common. This
      may have important implications for managing suspected appendicitis.

PMID- 8298380
TI  - Formal measurement of clinical uncertainty: prelude to a trial in perinatal
      medicine. The Fetal Compromise Group.

PMID- 8298381
TI  - Allopurinol interaction with cyclosporin.

PMID- 8298382
TI  - Fever, vasculitic rash, arthritis, pericarditis, and pericardial effusion after
      mesalazine.

PMID- 8298383
TI  - Myoclonus associated with propafenone.

PMID- 8298384
TI  - Building morale through personal development.
AB  - Once general practitioners have established themselves as principals it may seem
      there is little else to work for. Lack of stimulation may lead to demoralisation,
      and it is essential that they have other ways to continue to develop their
      careers. Meeting other doctors to discuss cases and problems and postgraduate
      education often help but many doctors want to take on extra roles. The options
      available include undergraduate teacher, tutor for postgraduate education, and
      participation in medical audit advisory groups, local medical committees, or
      royal college faculties. Some general practitioners work part time to allow them
      to fit in these activities. It may also be possible to obtain extended study
      leave or a sabbatical to broaden experience. Others even more practice to provide
      new challenges.

PMID- 8298385
TI  - An economic view of high compliance as a screening objective.
AB  - Accepted wisdom holds that high compliance is essential for a screening programme
      to be successful. Indeed, a reason that the national breast screening programme
      is not routinely offered to women aged 65 or more is on the grounds of predicted
      poor compliance by older women. Increasing compliance is often associated with
      increased costs. These costs represent a lost opportunity for screening
      alternative target populations. We question the need for screening programmes to
      achieve high compliance, and we argue that a screening programme can be efficient
      with very low levels of compliance. Adopting compliance as a screening objective
      and as a measure of the success of screening may be detrimental to the efficiency
      of a screening programme.

PMID- 8298386
TI  - Hypoxia in childhood pneumonia: better detection and more oxygen needed in
      developing countries.
AB  - Even though hypoxia is a major risk factor for death in children with acute
      respiratory infection in developing countries, oxygen is not part of first line
      treatment. Because oxygen is not readily available in developing countries it
      tends to be given to the most seriously ill children, whose outcome is poor.
      Oxygen might be useful if given earlier in the course of the disease. Clinical
      signs are not clear cut, however, though the presence of cyanosis and grunting
      together with a raised respiratory rate can significantly increase the detection
      of hypoxaemia. A simple oximeter would make detection easier, and oxygen
      concentrators are more cost effective than bottled oxygen. Ideally oxygen should
      be given to children in the early stages of clinical pneumonia to prevent
      deterioration.

PMID- 8298387
TI  - ABC of emergency radiology. The knee.

PMID- 8298388
TI  - Minimally invasive surgery. Neurosurgery.
AB  - The introduction of minimally invasive techniques has greatly improved results
      for intracranial neurosurgery. Stereotaxy and improved imaging techniques have
      reduced surgical trauma by allowing surgeons to plan the least damaging route to
      operative sites and by increasing surgical precision. Stereotaxy has also allowed
      brain biopsies to be taken from sites such as the brain stem, which were rarely
      sampled before because free hand biopsy was so dangerous. Brain tumours can now
      be treated by interstitial radiotherapy--stereotactic insertion of catheters into
      the lesion for loading of radioactive iodine--or radiosurgery--focusing of
      intense beams of radiation on lesions without needing surgical incisions.
      Endoscopic neurosurgery can be used to reach cavities such as the ventricular
      system or cystic tumours. With interventional neuroradiology fine catheters can
      be introduced into most vessels in the cranium for embolisation or dilatation.
      The development of augmentative functional neurosurgery means that movement
      disorders, epilepsy, and intractable pain can be treated with implanted
      neurostimulating electrodes. Future developments will probably include frameless
      stereotaxy, when the rigid attachment of stereotactic apparatus to the patient's
      head can be dispensed with, and at least partial automation of procedures such
      brain biopsy.

PMID- 8298389
TI  - Long-term management after splenectomy. National guidelines please.

PMID- 8298390
TI  - Long-term management after splenectomy. Widen criteria for vaccination.

PMID- 8298391
TI  - Long-term management after splenectomy. Lifelong penicillin unproved in trials...

PMID- 8298392
TI  - Long-term management after splenectomy. ... and may be ineffective.

PMID- 8298393
TI  - Long-term management after splenectomy. Americans recommend additional
      immunization.

PMID- 8298394
TI  - Long-term management after splenectomy. Fact sheets posters, and protocol cards
      available.

PMID- 8298395
TI  - Long-term management after splenectomy. Hyposplenic patients need prophylactic
      penicillin.

PMID- 8298396
TI  - Long-term management after splenectomy. ... has been amended.

PMID- 8298397
TI  - Long-term management after splenectomy. Consider prophylaxis in systematic lupus
      erythematosus.

PMID- 8298398
TI  - Long-term management after splenectomy. Consider HIV infection in
      thrombocytopenia.

PMID- 8298399
TI  - Cesarean section rates. Evaluate the reasons for surgery.

PMID- 8298400
TI  - Diabetes registers in general practice. College reports higher prevalence.

PMID- 8298401
TI  - Diabetes registers in general practice. Hungarian registers new and improved.

PMID- 8298402
TI  - Deregulating emergency contraception. Family planning nurses have useful skills.

PMID- 8298403
TI  - Deregulating emergency contraception. The alternative may be unwanted
      pregnancies.

PMID- 8298404
TI  - Non-redemption of prescriptions. Linked to poor consultations.

PMID- 8298405
TI  - Non-redemption of prescriptions. Homeless people miss out on prescribed
      treatment.

PMID- 8298406
TI  - Lp(a) lipoprotein and impaired glucose tolerance. Association poorly
      investigated.

PMID- 8298407
TI  - Health in Israeli occupied territories.

PMID- 8298408
TI  - Training for house officers.

PMID- 8298409
TI  - Health concerns in Kosovo.

PMID- 8298410
TI  - Overestimation of cost savings in prevention of osteoporosis.

PMID- 8298411
TI  - Resource implications of cancelled operations.

PMID- 8298412
TI  - Information management and patient privacy.

PMID- 8298413
TI  - No deception in symposium supplement.

PMID- 8298414
TI  - The aspirin papers.

PMID- 8298415
TI  - Who benefits from medical interventions?

PMID- 8298416
TI  - IgA nephropathy.

PMID- 8298417
TI  - Sunburn and melanoma: how strong is the evidence?

PMID- 8298419
TI  - The World Health Organization histological typing of odontogenic tumours.
      Introducing the second edition.

PMID- 8298420
TI  - On the differential diagnosis of clear cell tumours of the head and neck.
AB  - Clear cell tumours, both benign and malignant, derive from a diverse group of
      epithelial cell types including renal epithelium, keratinising epithelium,
      cutaneous adnexa, salivary glands, odontogenic epithelium, melanocytes and even
      mesenchymally derived cells of adipose and tendon sheath. In the head and neck,
      clear cell tumours represent a singular challenge to the pathologist since the
      classic morphological features of malignant neoplasia exemplified by cytological
      atypia are frequently absent in malignant clear cell variants, thereby excluding
      reliance on this histopathological hallmark for the establishment of a diagnosis.
      The differential diagnosis of both benign and malignant clear cell tumours must
      take into account patterns of growth as well as the phenotype of accompanying
      cell populations when attempting to arrive at a definitive histological
      diagnosis. In this review article, the histopathology of head and neck tumours
      that harbour significant clear cell populations will be compared and contrasted.

PMID- 8298421
TI  - Immunological phenomena in human oral carcinoma in India.

PMID- 8298422
TI  - Epidemic oro-facial Kaposi's sarcoma (eKS)--report on 124 cases.
AB  - Oro-facial epidemic Kaposi's sarcoma (eKS) was observed in 124 patients (123 homo
      /bisexual men, average age 37.9 years, and one 35-year-old transsexual patient).
      Average survival time was 1 year 9 months (range: 3 months 4 years 6 months).
      57.3% of the patients had died. The hard and/or soft palate, gingiva and tongue
      were most frequently affected, with falling frequency within these locations.
      Oral manifestations of eKS appear to be common; treatment modalities must be
      optimised.

PMID- 8298423
TI  - Radiation therapy and pain in patients with head and neck cancer.
AB  - Pain is commonly present at the time of diagnosis of head and neck cancer. Pain
      occurs in all patients treated for oropharyngeal cancer. This study examined the
      prevalence, severity and characteristics of pain in patients treated with
      radiation therapy for cancer involving the head and neck and oral cavity. Pain
      increases throughout the course of radiation and persists following treatment and
      in some patients continues for 6-12 months. Pain frequently requires systemic
      analgesics in addition to oral rinses.

PMID- 8298418
TI  - Collaborative overview of randomised trials of antiplatelet therapy--I:
      Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet
      therapy in various categories of patients. Antiplatelet Trialists' Collaboration.
AB  - OBJECTIVE: To determine the effects of "prolonged" antiplatelet therapy (that is,
      given for one month or more) on "vascular events" (non-fatal myocardial
      infarctions, non-fatal strokes, or vascular deaths) in various categories of
      patients. DESIGN: Overviews of 145 randomised trials of "prolonged" antiplatelet
      therapy versus control and 29 randomised comparisons between such antiplatelet
      regimens. SETTING: Randomised trials that could have been available by March
      1990. SUBJECTS: Trials of antiplatelet therapy versus control included about
      70,000 "high risk" patients (that is, with some vascular disease or other
      condition implying an increased risk of occlusive vascular disease) and 30,000
      "low risk" subjects from the general population. Direct comparisons of different
      antiplatelet regimens involved about 10,000 high risk patients. RESULTS: In each
      of four main high risk categories of patients antiplatelet therapy was definitely
      protective. The percentages of patients suffering a vascular event among those
      allocated antiplatelet therapy versus appropriately adjusted control percentages
      (and mean scheduled treatment durations and net absolute benefits) were: (a)
      among about 20,000 patients with acute myocardial infarction, 10% antiplatelet
      therapy v 14% control (one month benefit about 40 vascular events avoided per
      1000 patients treated (2P < 0.00001)); (b) among about 20,000 patients with a
      past history of myocardial infarction, 13% antiplatelet therapy v 17% control
      (two year benefit about 40/1000 (2P < 0.00001)); (c) among about 10,000 patients
      with a past history of stroke or transient ischaemic attack, 18% antiplatelet
      therapy v 22% control (three year benefit about 40/1000 (2P < 0.00001)); (d)
      among about 20,000 patients with some other relevant medical history (unstable
      angina, stable angina, vascular surgery, angioplasty, atrial fibrillation,
      valvular disease, peripheral vascular disease, etc), 9% v 14% in 4000 patients
      with unstable angina (six month benefit about 50/1000 (2P < 0.00001)) and 6% v 8%
      in 16,000 other high risk patients (one year benefit about 20/1000 (2P <
      0.00001)). Reductions in vascular events were about one quarter in each of these
      four main categories and were separately statistically significant in middle age
      and old age, in men and women, in hypertensive and normotensive patients, and in
      diabetic and nondiabetic patients. Taking all high risk patients together showed
      reductions of about one third in non-fatal myocardial infarction, about one third
      in non-fatal stroke, and about one third in vascular death (each 2P < 0.00001).
      There was no evidence that non-vascular deaths were increased, so in each of the
      four main high risk categories overall mortality was significantly reduced. The
      most widely tested antiplatelet regimen was "medium dose" (75-325 mg/day)
      aspirin. Doses throughout this range seemed similarly effective (although in an
      acute emergency it might be prudent to use an initial dose of 160-325 mg rather
      than about 75 mg). There was no appreciable evidence that either a higher aspirin
      dose or any other antiplatelet regimen was more effective than medium dose
      aspirin in preventing vascular events. The optimal duration of treatment for
      patients with a past history of myocardial infarction, stroke, or transient
      ischaemic attack could not be determined directly because most trials lasted only
      one, two, or three years (average about two years). Nevertheless, there was
      significant (2P < 0.0001) further benefit between the end of year 1 and the end
      of year 3, suggesting that longer treatment might well be more effective. Among
      low risk recipients of "primary prevention" a significant reduction of one third
      in non-fatal myocardial infarction was, however, accompanied by a non-significant
      increase in stroke. Furthermore, the absolute reduction in vascular events was
      much smaller than for high risk patients despite a much longer treatment period
      (4.4% antiplatelet therapy v 4.8% control; five year

PMID- 8298424
TI  - Hyperbaric oxygen and postradiation osteonecrosis of the mandible.
AB  - The clinical and dental records of 26 patients with the clinical diagnosis of
      postradiation osteonecrosis (PRON) managed with hyperbaric oxygen (HBO) were
      reviewed to determine the efficacy of HBO. 19 patients were male and 7 were
      female; age at the first HBO session ranged from 28 to 80 years (median 57.5
      years). All but 8 patients reviewed had some form of surgical management; 7 had
      mandibulectomy for PRON. As part of management, a total of 9-84 HBO sessions
      (median 35 sessions) was administered. 18 of the 26 patients ultimately achieved
      persistent mucosal and cutaneous coverage 1-84 months (median 24 months) after
      the first HBO session. 13 of the 26 patients met strict criteria for resolution
      of their disease; fully 21 of 26 patients had improved PRON status following HBO
      therapy. HBO treatment as part of a comprehensive management plan is safe and
      effective in the management of PRON.

PMID- 8298425
TI  - Human herpes simplex-1 and papillomavirus type 16 homologous DNA sequences in
      normal, potentially malignant and malignant oral mucosa.
AB  - We have tested a range of normal, potentially malignant and malignant oral
      mucosal biopsies tissues by Southern blot hybridisation analysis for the
      simultaneous presence of HSV-1 and HPV type 16 DNA sequences, both of which have
      been implicated as risk factors in oral carcinogenesis. The results show that:
      (1) 2/4 patients with lichen planus, 2/4 patients with non-specific keratosis,
      1/8 patients with oral carcinoma and 3/5 biopsy specimens of normal oral mucosa
      contained DNA sequences homologous to the HSV-1, Bam HI-G fragment. (2) HPV-16
      homologous DNA sequences were detected in 3/4 patients with lichen planus, 4/4
      non-specific keratosis, 4/8 oral carcinomas and in 3/5 biopsy specimens of normal
      oral mucosa. (3) Overall, only 5 patient biopsy specimens were positive for both
      HSV-1 and HPV-16 homologous DNA sequences; 2 lichen planus, 2 non-specific
      keratosis and 1 normal. The data cannot exclude a "hit and run" oncogenic
      mechanism for HSV but suggest that if HSV-1 and HPV-16 play a synergistic role in
      the development of oral cancer this may be an early event. Indeed, the data
      suggest HSV might be more frequently found in potentially malignant lesions than
      in carcinoma.

PMID- 8298426
TI  - Adenomatoid odontogenic tumour with features of calcifying epithelial odontogenic
      tumour. (The so-called combined epithelial odontogenic tumour.) Clinico
      pathological report of 12 cases.
AB  - The combination of two odontogenic tumours is a rarely reported finding. To date
      only 10 cases of adenomatoid odontogenic tumour (AOT) combined with areas of
      calcifying epithelial odontogenic tumour (CEOT) have been published. This article
      describes the clinical, radiographical and microscopic findings of 12 cases of
      AOT, in which CEOT-like areas of variable sizes were found. These results suggest
      that such areas may be considered as a normal feature within the
      histomorphological spectrum of AOT.

PMID- 8298427
TI  - Oral presentation of lymphoma: case report of T-cell lymphoma masquerading as
      oral Crohn's disease, and review of the literature.
AB  - A 15-year-old male with labial swelling, mouth ulcers and mucosal tags is
      reported. While the features were clinically consistent with oral Crohn's disease
      the patient proved to have a fatal T-cell lymphocytic lymphoma.

PMID- 8298428
TI  - Electron microscopic immunolocalization of GABA and glutamic acid decarboxylase
      (GAD) in cerebellar capillaries and their microenvironment.
AB  - At present, it is known that a connection exists between neuronal activity and
      microvascular blood flow and permeability in the CNS. We have demonstrated the
      presence of immunoreactivities against both GABA and GAD as well in the
      endothelial capillary cells of rat cerebellar cortex, as in perivascular glia,
      neuronal bodies, dendrites and axon endings, in close association with the basal
      membrane of the pericyte or endothelial cells. These results support the
      suggestions from biochemical and pharmacological studies about the relationship
      between GABA and microvascular function in the CNS.

PMID- 8298429
TI  - Molecular and ultrastructural basis of the blood-brain barrier function.
      Immunohistochemical demonstration of Na+/K+ ATPase, alpha-actin, phosphocreatine
      and clathrin in the capillary wall and its microenvironment.
AB  - Cerebral capillaries represent the responsible structure for the establishment of
      the BBB. We have demonstrated the presence within both pericytes and endothelial
      cells of abundant cytoplasmic vesicles. We have noticed the presence of Na+/K(+)
      ATPase-, alpha-actin-, phosphocreatine- and clathrin-like molecules within
      cerebellar capillaries and their microenvironment. These facts suggest the
      importance of the contractile and transport mechanisms in the blood-brain
      barrier. We have also demonstrated the close contact between different nervous
      components of the cerebellar cortex with the basement membrane that surrounds
      capillary wall. We suggest that these observations represent the morphological
      evidence of neurogenic control of brain circulation.

PMID- 8298430
TI  - Immune activation of guinea pig lymphocytes type "cerebriform" and type "hand
      mirror". An ultrastructural study.
AB  - The fine structure of lymphocytes type "cerebriform" and type "hand mirror" from
      guinea pigs was analyzed. The cells were isolated from three groups of animals,
      immunized with BCG, F. tularensis (LVS) or plague vaccine (EV-Brubaker),
      respectively, and stimulated in vitro with the corresponding antigen six weeks
      after the immunizations. Both, the "cerebriform" and "hand mirror" lymphocytes
      were present in the T-cell fractions but not in the B-cell ones. Upon
      stimulation, these types of cells reacted uniformly, independently of the antigen
      used. This was expressed in cell volume increase, inversion of the nucleo
      cytoplasm index, proliferation of organelles, hypertrophy of the Golgi complex,
      dispersion of the nuclear chromatin and an increase of the number of cytoplasmic
      projections. According to ultrastructural characteristics the subpopulation of
      the "cerebriform" lymphocytes was non-uniform. It is possible that some of the
      cells express cytotoxic functions.

PMID- 8298431
TI  - X-ray microanalysis of guinea pigs peripheral blood T and B lymphocytes: before
      and after antigen stimulation.
AB  - T and B lymphocytes from with Francisella tularensis (LVS) immunized guinea pigs
      were separated and stimulated in vitro with the specific antigen. Their chemical
      composition was studied in comparison by X-ray microanalysis before and after
      stimulation. Different elemental spectra of normal T, B and T-suppressor cells
      were obtained. The common elements were P, S, K, Cl and As; I was present only in
      B cells; Cr and Na were detected only in T suppressor cells. After stimulation
      the spectra of these three types of lymphocytes differed both from the original
      normal ones and in between. I disappeared in the spectrum of B cells but the
      peaks of P and Cl raised up; the peaks of S and P were higher in the activated T
      cells along with the appearance of Na and Si; an increase of the peak of Cl in
      the spectrum of T suppressor cells was revealed on the 21st day after the
      immunization. The registered differences in the chemical composition of the
      stimulated lymphocyte populations are possibly connected with the different type
      of response to the antigen stimulation.

PMID- 8298432
TI  - Changes in distribution of lectin receptors in macrophages activated by Nocardia
      water soluble molecules.
AB  - Lectin-histochemical studies were performed on macrophages activated by Nocardia
      opaca water soluble molecules (NWSM) and elicited by phosphate buffered saline
      (PBS) as control to demonstrate the pattern of carbohydrate residues. Ten
      different biotinylated lectins were used as probes and avidin-biotin-peroxidase
      complex (ABC) was used as visualizer. The lectins wheat germ agglutinin (WGA) and
      Griffonia simplicifolia agglutinin-I (GS-I) stained macrophages only after
      activation by NWSM and not macrophages elicited by PBS. Both macrophages did not
      stain by succinylated wheat germ agglutinin (S-WGA). The difference in lectin
      binding patterns between NWSM-activated and PBS-elicited macrophages, suggests
      that activation of macrophages by the NWSM is associated with modification in the
      distribution of specific membrane carbohydrates, including enhancement in the
      expression of sialyl and alpha-galactosyl residues.

PMID- 8298433
TI  - Thermal behaviour of the rabbit sublingual gland.
AB  - The purpose of this study was to show how some aspects of the biological matrix
      water can be investigated by thermoanalytical methods when using thermogravimetry
      and differential scanning calorimetry. Such methods allow to investigate the
      water in the rabbit sublingual gland and to quantitate it. The results supported
      the view that the water contained in this secretory organ show a large number of
      energetic interactions established on the basis of differential steps of water
      release by thermal disruption.

PMID- 8298434
TI  - Effects of DNA damaging agents on gene expression in two human cancer cell lines.
AB  - In two human cancer cell lines, the breast mcf-7 and the T-cell leukemia MOLT4,
      we investigated the cytotoxicity of four antineoplastic agents having different
      mechanisms of action. We selected doxorubicin as a DNA-topoisomerase II
      inhibitor, FCE24517 (a Distamycin A derivative) as a DNA minor groove binder with
      specificity for AT bases, melphalan as an alkylating agent and cis-platinum as an
      alkylating agent able to form DNA-intrastrand crosslinks. From the cytotoxicity
      experiments a moderately toxic (less than 10% of growth inhibition) and a highly
      toxic (about 75% growth inhibition) dose were selected to evaluate the expression
      of genes involved in cell proliferation and in cell response to extracellular
      insults. The expression was evaluated at early times (60 min.) and 24 hrs. after
      treatment. At the concentrations utilized in both cell lines we could not find
      any alteration in the expression of p53, gas-1 and heat shock 70. After melphalan
      treatment down regulation of c-myc and of the H2A histone was seen at high doses,
      while no significant alteration of their expression was seen with the other
      drugs.

PMID- 8298435
TI  - Conventional and high resolution field emission scanning electron microscopy of
      vertebrate cerebellar parallel fiber-Purkinje spine synapses.
AB  - Purkinje dendrite-parallel fiber spine synapses of human, teleost fishes, Rhesus
      monkey and mouse cerebellar cortex have been studied by means of conventional
      scanning electron microscopy (SEM) using ethanol-cryofracturing technique and by
      high resolution field emission scanning electron microscopy (HRFESEM) for
      studying the outer and inner surface morphology of pre- and postsynaptic endings.
      Transmission electron microscopy of mouse cerebellar cortex either by means of
      ultrathin sections and freeze-etching replicas have been complementarily used for
      proper identification and comparative observations. Normal teleost fishes showed
      short neck and neckless Purkinje spines with exhibited spread or extended
      postsynaptic densities. In pathological human cerebellum, the ethanol
      cryofracturing technique exposed the outer surface of edematous flat and
      invaginated Purkinje spine synapses. In fractured presynaptic endings HRFESEM
      showed in Rhesus monkey cerebellar cortex a homogeneous extravesicular material
      binded to the synaptic vesicles and joining them to the presynaptic membrane.
      HRFESEM partially resolved the synaptic cleft as currently observed in high
      magnification transmission electron microscopy. Round subunits, 25-35 nm in
      diameter, were observed associated to postsynaptic membrane, apparently
      corresponding to the localization and distribution of E face postsynaptic
      intramembrane particles, which suggest that such subunits correspond to the
      domains of neurotransmitter postsynaptic receptors.

PMID- 8298436
TI  - Radioautographic study on the aging change of 3H-glucosamine uptake in mouse
      ileum.
AB  - The changes of the localization of incorporated glucosamine in mice ilea due to
      aging were studied by light microscopic radioautography in 10 groups of mice from
      fetus (19th day of embryo) to senescent (postnatal 2 years). After
      intraperitoneal injection of 6-3H-D-glucosamine the ilea of respective age groups
      were taken out and processed for light microscopic radioautography. The numbers
      of silver grains were counted at each part of ileal mucosal cells. The results
      show that the silver grains of columnar epithelial cells were localized mainly on
      brush border and Golgi region, and the grains of goblet cells were localized on
      Golgi region and mucous granules. Comparing the intestinal villi and crypts, the
      uptake of columnar epithelial cells and villi goblet cells was higher than these
      cells in crypt. The number of grains in respective age groups increased from
      perinatal to mature adults due to aging.

PMID- 8298437
TI  - Screening survey of several plant species in search for ribosome-inactivating
      protein-like activities.
AB  - A screening survey of 41 plants revealed potent translational inhibitory
      activities in 19 plant species belonging to several different families, some of
      them hitherto unreported. Our results indicate that the active principles were
      ribosome-inactivating proteins. Additionally, human erythrocyte-agglutinating
      activity was found in 20 plants.

PMID- 8298438
TI  - Physiological bases of breast cancer prevention.
AB  - The relevance of this work lies in the possibility of extrapolating conclusions
      drawn here to the human situation, since we have assessed the validity of the rat
      model for the study of breast cancer in women through comparative studies in
      these two species (Russo and Russo, 1988). The novelty of our studies is the
      evidence that hCG protects the mammary gland against carcinogenic initiation and
      progression, mimicking the physiological process of pregnancy, without crippling
      other reproductive or endocrine functions (Russo et al, 1990d; Russo and Russo,
      1992). The importance of both differentiation and cell proliferation in tumour
      initiation and progression, which we have stressed in previous publications
      (Russo and Russo, 1980, 1987, 1988; Russo et al, 1982) validates the use of these
      end-points for assessing the effect of hormones under the influence of hCG on the
      mammary gland initiated in the process of carcinogenesis. Collectively, our
      results provide solid bases for developing physiological means of breast cancer
      prevention and control.

PMID- 8298439
TI  - Morphology of the premalignant lesions of the breast.

PMID- 8298440
TI  - Benign breast diseases: risk factor or precancerous state?

PMID- 8298441
TI  - An epidemiologist's view on precancerous lesions in the human breast.

PMID- 8298442
TI  - The involvement of genetic factors in susceptibility to breast cancer.

PMID- 8298443
TI  - The early detection of disseminated (metastasized) breast cancer by serial tumour
      marker measurements.

PMID- 8298444
TI  - Chemoprevention of breast cancer.

PMID- 8298445
TI  - Tamoxifen in premalignant and pre-invasive breast cancer.

PMID- 8298446
TI  - Evidence for premalignant lesions in the human breast.

PMID- 8298447
TI  - Contribution of cytology in the detection of preneoplastic lesions and
      noninvasive breast cancer.

PMID- 8298448
TI  - Characterization of tumour infiltrating lymphocytes in human breast cancer.

PMID- 8298449
TI  - Epidemiological survey of preinvasive breast cancer.
AB  - DCIS and LCIS are different breast diseases at various points of view. DCIS has
      in most cases a clinical or mammographical pattern, whereas LCIS represents an
      incidental finding in breast tissue removed for another reason. However, DCIS
      found incidental to benign disease may be a more innocuous form of tumour.
      Multifocal foci are more frequent in LCIS than in DCIS, but microinvasion and
      coexisting unsuspected infiltration carcinoma are more often found in DCIS.
      Contralateral in situ breast carcinoma is a rare event in DCIS. It is seldom
      found in LCIS. The risk of development of an infiltrating ipsilateral carcinoma
      after biopsy or excision showing in situ carcinoma is higher for DCIS than for
      LCIS. However, in most cases the invasive tumour occurs at or near the site of
      the original biopsy. Among LCIS patients, invasive carcinoma occurs anywhere in
      the breast parenchyma. The risk of development of contralateral invasive cancer
      is very low in DCIS patients, but it is high in LCIS patients. It may be lobular,
      ductal or a mixture of different types. DCIS has to be considered as a truly
      preinvasive lesion although LCIS is rather a marker of increased risk.

PMID- 8298450
TI  - A comparison of the epidemiology of atypical hyperplasia of the breast epithelium
      and mammographic parenchymal densities.

PMID- 8298451
TI  - The role of the pathologist in dissecting the biology of breast cancer with
      special reference to in situ disease.

PMID- 8298452
TI  - Short-term results of a new programme for breast carcinoma risk analysis.

PMID- 8298453
TI  - NMR and protein folding: equilibrium and stopped-flow studies.
AB  - NMR studies are now unraveling the structure of intermediates of protein folding
      using hydrogen-deuterium exchange methodologies. These studies provide
      information about the time dependence of formation of secondary structure. They
      require the ability to assign specific resonances in the NMR spectra to specific
      amide protons of a protein followed by experiments involving competition between
      folding and exchange reactions. Another approach is to use 19F-substituted amino
      acids to follow changes in side-chain environment upon folding. Current
      techniques of molecular biology allow assignments of 19F resonances to specific
      amino acids by site-directed mutagenesis. It is possible to follow changes and to
      analyze results from 19F spectra in real time using a stopped-flow device
      incorporated into the NMR spectrometer.

PMID- 8298454
TI  - Thermodynamics of unfolding for turkey ovomucoid third domain: thermal and
      chemical denaturation.
AB  - We have used thermal and chemical denaturation to characterize the thermodynamics
      of unfolding for turkey ovomucoid third domain (OMTKY3). Thermal denaturation was
      monitored spectroscopically at a number of wave-lengths and data were subjected
      to van't Hoff analysis; at pH 2.0, the midpoint of denaturation (Tm) occurs at
      58.6 +/- 0.4 degrees C and the enthalpy of unfolding at this temperature (delta
      Hm) is 40.8 +/- 0.3 kcal/mol. When Tm was perturbed by varying pH and denaturant
      concentration, the resulting plots of delta Hm versus Tm yield a mean value of
      590 +/- 120 cal/(mol.K) for the change in heat capacity upon unfolding (delta
      Cp). A global fit of the same data to an equation that includes the temperature
      dependence for the enthalpy of unfolding yielded a value of 640 +/- 110
      cal/(mol.K). We also performed a variation of the linear extrapolation method
      described by Pace and Laurents, which is an independent method for determining
      delta Cp (Pace, C.N. & Laurents, D., 1989, Biochemistry 28, 2520-2525). First,
      OMTKY3 was thermally denatured in the presence of a variety of denaturant
      concentrations. Linear extrapolations were then made from isothermal slices
      through the transition region of the denaturation curves. When extrapolated free
      energies of unfolding (delta Gu) were plotted versus temperature, the resulting
      curve appeared linear; therefore, delta Cp could not be determined. However, the
      data for delta Gu versus denaturant concentration are linear over an
      extraordinarily wide range of concentrations. Moreover, extrapolated values of
      delta Gu in urea are identical to values measured directly.

PMID- 8298455
TI  - Local and nonlocal interactions in globular proteins and mechanisms of alcohol
      denaturation.
AB  - How important are helical propensities in determining the conformations of
      globular proteins? Using the two-dimensional lattice model and two monomer types,
      H (hydrophobic) and P (polar), we explore both nonlocal interactions, through an
      HH contact energy, epsilon, as developed in earlier work, and local interactions,
      through a helix energy, sigma. By computer enumeration, the partition functions
      for short chains are obtained without approximation for the full range of both
      types of energy. When nonlocal interactions dominate, some sequences undergo coil
      globule collapse to a unique native structure. When local interactions dominate,
      all sequences undergo helix-coil transitions. For two different conformational
      properties, the closest correspondence between the lattice model and proteins in
      the Protein Data Bank is obtained if the model local interactions are made small
      compared to the HH contact interaction, suggesting that helical propensities may
      be only weak determinants of globular protein structures in water. For some HP
      sequences, varying sigma/epsilon leads to additional sharp transitions (sometimes
      several) and to "conformational switching" between unique conformations. This
      behavior resembles the transitions of globular proteins in water to helical
      states in alcohols. In particular, comparison with experiments shows that whereas
      urea as a denaturant is best modeled as weakening both local and nonlocal
      interactions, trifluoro-ethanol is best modeled as mainly weakening HH
      interactions and slightly enhancing local helical interactions.

PMID- 8298456
TI  - Characterization of the NR1, NR2A, and NR2C receptor proteins.
AB  - N-Methyl-D-aspartate (NMDA) receptor subunits were characterized with seven
      polyclonal antibodies. The antibodies were directed against NR1-A, NR2A-N1, and
      NR2C-N1, representing N-terminal sequences of the NR1, NR2A, and NR2C subunits,
      and against NR1-E, NR2A-C1, and NR2C-C1, derived from C-terminal sequences of
      these subunits. The anti-NR1-D antibody was raised against the putative internal
      loop of NR1. A size of 118 kDa was found in sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis for NR1 (from rat brain) detected by anti-NR1-D and -NR1-E,
      but not anti-NR1-A. With the anti-NR1-A antibody, a 125-kDa protein was
      discovered that may represent a glutamate receptor not yet characterized. NR2A
      and NR2C were identified as proteins with sizes of 175 and 140 kDa, respectively.
      Enzymatic N-deglycosylation generated a 97-kDa protein from NR1, a 105-kDa
      protein from the 125-kDa protein, a 162-kDa protein from NR2A, and a 127-kDa
      protein from NR2C. In contrast to the deglycosylation product of the NR2A, the 97
      and 127-kDa proteins derived from NR1 and NR2C, respectively, were found
      significantly smaller than the molecular masses of 103 and 141 kDa, respectively,
      predicted on the basis of DNA data. These products may represent truncated
      proteins. The tissue content of the NR1 and NR2A was high in bovine hippocampus
      and cortex but lower in the cerebellum. In contrast, NR2C was solely found in the
      cerebellum. The 125-kDa protein was highest in the cerebellum and cortex.

PMID- 8298457
TI  - Structure and orientation of the antibiotic peptide magainin in membranes by
      solid-state nuclear magnetic resonance spectroscopy.
AB  - Magainin 2 is a 23-residue peptide that forms an amphipathic alpha-helix in
      membrane environments. It functions as an antibiotic and is known to disrupt the
      electrochemical gradients across the cell membranes of many bacteria, fungi, and
      some tumor cells, although it does not lyse red blood cells. One- and two
      dimensional solid-state 15N NMR spectra of specifically 15N-labeled magainin 2 in
      oriented bilayer samples show that the secondary structure of essentially the
      entire peptide is alpha-helix, immobilized by its interactions with the
      phospholipids, and oriented parallel to the membrane surface.

PMID- 8298458
TI  - Fluorescence characterization of Trp 21 in rat glutathione S-transferase 1-1:
      microconformational changes induced by S-hexyl glutathione.
AB  - The glutathione S-transferase (GST) isoenzyme A1-1 from rat contains a single
      tryptophan, Trp 21, which is expected to lie within alpha-helix 1 based on
      comparison with the X-ray crystal structures of the pi- and mu-class enzymes.
      Steady-state and multifrequency phase/modulation fluorescence studies have been
      performed in order to characterize the fluorescence parameters of this tryptophan
      and to document ligand-induced conformational changes in this region of the
      protein. Addition of S-hexyl glutathione to GST isoenzyme A1-1 causes an increase
      in the steady-state fluorescence intensity, whereas addition of the substrate
      glutathione has no effect. Frequency-domain excited-state lifetime measurements
      indicate that Trp 21 exhibits three exponential decays in substrate-free GST. In
      the presence of S-hexyl glutathione, the data are also best described by the sum
      of three exponential decays, but the recovered lifetime values change. For the
      substrate-free protein, the short lifetime component contributes 9-16% of the
      total intensity at four wavelengths spanning the emission. The fractional
      intensity of this lifetime component is decreased to less than 3% in the presence
      of S-hexyl glutathione. Steady-state quenching experiments indicate that Trp 21
      is insensitive to quenching by iodide, but it is readily quenched by acrylamide.
      Acrylamide-quenching experiments at several emission wavelengths indicate that
      the long-wavelength components become quenched more easily in the presence of S
      hexyl glutathione. Differential fluorescence polarization measurements also have
      been performed, and the data describe the sum of two anisotropy decay rates. The
      recovered rotational correlation times for this model are 26 ns and 0.81 ns,
      which can be attributed to global motion of the protein dimer, and fast local
      motion of the tryptophan side chain. These results demonstrate that regions of
      GST that are not in direct contact with bound substrates are mobile and undergo
      microconformational rearrangement when the "H-site" is occupied.

PMID- 8298459
TI  - MIF protein are theta-class glutathione S-transferase homologs.
AB  - MIF proteins are mammalian polypeptides of approximately 13,000 molecular weight.
      This class includes human macrophage migration inhibitory factor (MIF), a rat
      liver protein that has glutathione S-transferase (GST) activity (TRANSMIF), and
      the mouse delayed early response gene 6 (DER6) protein. MIF proteins were
      previously linked to GSTs by demonstrating transferase activity and observing N
      terminal sequence homology with a mu-class GST (Blocki, F.A., Schlievert, P.M., &
      Wackett, L.P., 1992, Nature 360, 269-270). In this study, MIF proteins are shown
      to be structurally related to the theta class of GSTs. This is established in
      three ways. First, unique primary sequence patterns are developed for each of the
      GST gene classes. The patterns identify the three MIF proteins as theta-like
      transferase homologs. Second, pattern analysis indicates that GST members of the
      theta class contain a serine residue in place of the N-terminal tyrosine that is
      implicated in glutathione deprotonation and activation in GSTs of known structure
      (Liu, S., et al., 1992, J. Biol. Chem. 267, 4296-4299). The MIF proteins contain
      a threonine at this position. Third, polyclonal antibodies raised against
      recombinant human MIF cross-react on Western blots with rat theta GST but not
      with alpha and mu GSTs. That MIF proteins have glutathione-binding ability may
      provide a common structural key toward understanding the varied functions of this
      widely distributed emerging gene family. Because theta is thought to be the most
      ancient evolutionary GST class, MIF proteins may have diverged early in evolution
      but retained a glutathione-binding domain.

PMID- 8298460
TI  - Structural prototypes for an extended family of flavoprotein reductases:
      comparison of phthalate dioxygenase reductase with ferredoxin reductase and
      ferredoxin.
AB  - The structure of phthalate dioxygenase reductase (PDR), a monomeric iron-sulfur
      flavoprotein that delivers electrons from NADH to phthalate dioxygenase, is
      compared to ferredoxin-NADP+ reductase (FNR) and ferredoxin, the proteins that
      reduce NADP+ in the final reaction of photosystem I. The folding patterns of the
      domains that bind flavin, NAD(P), and [2Fe-2S] are very similar in the two
      systems. Alignment of the X-ray structures of PDR and FNR substantiates the
      assignment of features that characterize a family of flavoprotein reductases
      whose members include cytochrome P-450 reductase, sulfite and nitrate reductases,
      and nitric oxide synthase. Hallmarks of this subfamily of flavoproteins, here
      termed the FNR family, are an antiparallel beta-barrel that binds the flavin
      prosthetic group, and a characteristic variant of the classic pyridine nucleotide
      binding fold. Despite the similarities between FNR and PDR, attempts to model the
      structure of a dissociable FNR:ferredoxin complex by analogy with PDR reveal
      features that are at odds with chemical crosslinking studies (Zanetti, G.,
      Morelli, D., Ronchi, S., Negri, A., Aliverti, A., & Curti, B., 1988, Biochemistry
      27, 3753-3759). Differences in the binding sites for flavin and pyridine
      nucleotides determine the nucleotide specificities of FNR and PDR. The
      specificity of FNR for NADP+ arises primarily from substitutions in FNR that
      favor interactions with the 2' phosphate of NADP+. Variations in the conformation
      and sequences of the loop adjoining the flavin phosphate affect the selectivity
      for FAD versus FMN. The midpoint potentials for reduction of the flavin and [2Fe
      2S] groups in PDR are higher than their counterparts in FNR and spinach
      ferredoxin, by about 120 mV and 260 mV, respectively. Comparisons of the
      structure of PDR with spinach FNR and with ferredoxin from Anabaena 7120, along
      with calculations of electrostatic potentials, suggest that local interactions,
      including hydrogen bonds, are the dominant contributors to these differences in
      potential.

PMID- 8298461
TI  - Origins of structural diversity within sequentially identical hexapeptides.
AB  - Efforts to predict protein secondary structure have been hampered by the apparent
      structural plasticity of local amino acid sequences. Kabsch and Sander (1984,
      Proc. Natl. Acad. Sci. USA 81, 1075-1078) articulated this problem by
      demonstrating that identical pentapeptide sequences can adopt distinct structures
      in different proteins. With the increased size of the protein structure database
      and the availability of new methods to characterize structural environments, we
      revisit this observation of structural plasticity. Within a set of proteins with
      less than 50% sequence identity, 59 pairs of identical hexapeptide sequences were
      identified. These local structures were compared and their surrounding structural
      environments examined. Within a protein structural class (alpha/alpha, beta/beta,
      alpha/beta, alpha + beta), the structural similarity of sequentially identical
      hexapeptides usually is preserved. This study finds eight pairs of identical
      hexapeptide sequences that adopt beta-strand structure in one protein and alpha
      helical structure in the other. In none of the eight cases do the members of
      these sequences pairs come from proteins within the same folding class. These
      results have implications for class dependent secondary structure prediction
      algorithms.

PMID- 8298462
TI  - Classification of doubly wound nucleotide binding topologies using automated loop
      searches.
AB  - A classification is presented of doubly wound alpha/beta nucleotide binding
      topologies, whose binding sites are located in the cleft formed by a topological
      switch point. In particular, the switch point loop nearest the N-terminus is used
      to identify specific structural classes of binding protein. This yields seven
      structurally distinct loop conformations, which are subsequently used as motifs
      for scanning the Protein Data Bank. The searches, which are effective at
      identifying functional relationships within a large database of structures,
      reveal a remarkable and previously unnoticed similarity between the coenzyme
      binding sites of flavodoxin and tryptophan synthetase, even though there is no
      sequence or topological similarity between them.

PMID- 8298463
TI  - Divalent metal ions influence catalysis and active-site accessibility in the cAMP
      dependent protein kinase.
AB  - Phosphorylation of the peptide LRRASLG by the catalytic subunit of cAMP-dependent
      protein kinase was measured in the presence of various divalent metals to
      establish the role of electrophiles in the kinetic mechanism. Under conditions of
      low or high metal concentrations, the apparent second-order rate constant,
      kcat/Kpeptide, and the maximal rate constant, kcat, followed the trend Mg2+ >
      Co2+ > Mn2+. Competitive inhibition studies indicate that the former effect is
      not due to destabilization of the substrate complex, E.ATP.S. The effects of
      solvent viscosity on the steady-state kinetic parameters were interpreted
      according to a simple mechanism involving substrate binding, phosphotransfer, and
      product release steps and two metal chelation sites in the nucleotide pocket.
      Decreases in kcat and kcat/Kpeptide result mostly from attenuations in the
      dissociation rate constant for ADP and the association rate constant for the
      substrate, respectively. Decreases in the phosphoryl transfer rate constant have
      only negligible to moderate effects on these parameters. The low observed values
      for the association rate constant of the substrate indicate that the metals
      control the concentration of the productive binary form, Ea.ATP, and indirectly
      the accessibility of the active site. By comparison, Mg2+ is the best divalent
      metal catalyst because it uniformly lowers the transition state energies for all
      steps in the kinetic mechanism, permitting maximum flux of substrate to product.
      The data suggest that cAMP-dependent protein kinase uses metal ions to serve
      multiple roles in facilitating phosphotransfer and accelerating substrate
      association and product dissociation.

PMID- 8298464
TI  - Probing weakly polar interactions in cytochrome c.
AB  - Theoretical, statistical, and model studies suggest that proteins are stabilized
      by weakly polar attractions between sulfur atoms and properly oriented aromatic
      rings. The two sulfur-containing amino acids, methionine and cysteine, occur
      frequently among functional alleles in random mutant libraries of Saccharomyces
      cerevisiae iso-1-cytochrome c genes at positions that form a weakly polar
      aromatic-aromatic interaction, the wild-type protein. To determine if a weakly
      polar sulfur-aromatic interaction replaced the aromatic-aromatic interaction, the
      structure and stability of two variants were examined. Phenylalanine 10, which
      interacts with tyrosine 97, was replaced by methionine and cysteine. The cysteine
      was modified to form the methionine and cysteine analog, S-methyl cysteine
      (CysSMe). Proton NMR studies indicate that changing Phe 10 to Met or CysSMe
      affects only local structure and that the structures of sulfur-containing
      variants are nearly identical. Analysis of chemical shifts and nuclear Overhauser
      effect data indicates that both sulfur-containing side chains are in position to
      form a weakly polar interaction with Tyr 97. The F10M and F10CSMe variants are 2
      3 kcal mol-1 less stable than iso-1-cytochrome c at 300 K. Comparison of the
      stabilities of the F10M and F10CSMe variants allows evaluation of the potential
      weakly polar interaction between the additional sulfur atom of F10CSMe and the
      aromatic moiety of Tyr 97. The F10CSMe;C102T variant is 0.7 +/- 0.3 kcal mol-1
      more stable than the F10M;C102T protein. The increased stability is explained by
      the difference in hydrophobicity of the sulfur-containing side chains. We
      conclude that any weakly polar interaction between the additional sulfur and the
      aromatic ring is too weak to detect or is masked by destabilizing contributions
      to the free energy of denaturation.

PMID- 8298465
TI  - P22 Arc repressor: enhanced expression of unstable mutants by addition of polar C
      terminal sequences.
AB  - Many mutant variants of the P22 Arc repressor are subject to intracellular
      proteolysis in Escherichia coli, which precludes their expression at levels
      sufficient for purification and subsequent biochemical characterization. Here we
      examine the effects of several different C-terminal extension sequences on the
      expression and activity of a set of Arc mutants. We show that two tail sequences,
      KNQHE (st5) and H6KNQHE (st11), increase the expression levels of most mutants
      from 10- to 20-fold and, in some cases, result in restoration of biological
      activity in the cell. A third tail sequence, HHHHHH (st6), was not as effective
      in increasing mutant expression levels. All three tail sequences are functionally
      and structurally silent, as judged by their lack of effects on the DNA binding
      activity and stability of otherwise wild-type Arc. The properties of the st11
      tail sequence make it an efficient system for the expression and purification of
      mutant Arc proteins, both because mutant expression levels are increased and
      because the proteins can be rapidly purified using nickel-chelate affinity
      chromatography. Arc mutants containing the EA28, RL31, and SA32 mutations were
      purified in the st11 background. The thermodynamic stability of the EA28 mutant
      (delta delta Gu approximately -0.4 kcal/mol) is reduced modestly compared to the
      st11 parent, whereas the RL31 mutant (delta delta Gu approximately -3.0 kcal/mol)
      and SA32 mutant (delta delta Gu approximately -3.3 kcal/mol) are substantially
      less stable.

PMID- 8298466
TI  - Structures of randomly generated mutants of T4 lysozyme show that protein
      stability can be enhanced by relaxation of strain and by improved hydrogen
      bonding via bound solvent.
AB  - The structures of three mutants of bacteriophage T4 lysozyme selected using a
      screen designed to identify thermostable variants are described. Each of the
      mutants has a substitution involving threonine. Two of the variants, Thr 26-->Ser
      (T26S) and Thr 151-->Ser (T151S), have increased reversible melting temperatures
      with respect to the wild-type protein. The third, Ala 93-->Thr (A93T), has
      essentially the same stability as wild type. Thr 26 is in the wall of the active
      site cleft. Its replacement with serine results in the rearrangement of nearby
      residues, most notably Tyr 18, suggesting that the increase in stability may
      result from the removal of strain. Thr 151 in the wild-type structure is far from
      the active site and appears to sterically prevent the access of solvent to a
      preformed binding site. In the mutant, the removal of the methyl group allows
      access to the solvent binding site and, in addition, the Ser 151 hydroxyl rotates
      to a new position so that it also contributes to solvent binding. Residue 93 is
      in a highly exposed site on the surface of the molecule, and presumably is
      equally solvent exposed in the unfolded protein. It is, therefore, not surprising
      that the substitution Ala 93-->Thr does not change stability. The mutant
      structures show how chemically similar mutations can have different effects on
      both the structure and stability of the protein, depending on the structural
      context. The results also illustrate the power of random mutagenesis in obtaining
      variants with a desired phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298467
TI  - Dynamics of interaction of RNA polymerase II with nucleosomes. I. Effect of
      salts.
AB  - Mononucleosomes were labeled with the sulfhydryl-specific fluorescence probe 1,5
      IAEDANS (5-(2-((iodoacetyl)amino)ethyl)amino-naphthalene-1-sulfonic acid) by
      attaching the dye to the single cysteine of H3 through a covalent linkage. The
      enzyme RNA polymerase II (pol II) utilized the native and the reconstituted
      fluorescent nucleosomes as templates with greatest efficiency when 0.2 M
      potassium acetate (AcOK) was used as the supporting salt; 0.2 M NaCl was found to
      be very much inhibitory. Measurement of polarity of the microenvironment of the
      dye at its binding site in the nucleosome showed the conformation to be more open
      in the presence of AcOK, compared to that in 0.1 or 0.2 M NaCl. The binding of
      pol II to the nucleosome resulted in a relatively more compact structure when
      measured in terms of the polarity of the microenvironment of the dye in various
      salt-dependent conformations of the nucleosomes. Time-resolved fluorescence
      spectroscopy showed that the probe molecule at its binding site undergoes certain
      excited-state processes, and the presence/absence or rate of these excited-state
      processes depends on the conformation of nucleosomes, which in turn depends on
      the type and concentration of the ion present in the medium. Time-resolved
      emission spectra showed that binding of nucleosomes by pol II established some
      new contacts that resulted in inaccessibility of the dye to the bulk solvent,
      reflecting a more hydrophobic environment for the dye in the steady-state
      spectra. Thus, binding or transcription of nucleosomes by pol II did not break
      open their structure. Rather, some transient internal adjustments within the
      histone octamer may take place to accommodate the bulky pol II molecule.

PMID- 8298468
TI  - Dynamics of interaction of RNA polymerase II with nucleosomes. II. During read
      through and elongation.
AB  - The sulfhydryl-specific fluorescence probe 1,5-IAEDANS (5-(2
      ((iodoacetyl)amino)ethyl)amino-naphthalene-1-sulfonic acid) was attached to the
      single cysteine of H3, and reconstituted fluorescent mononucleosomes were used as
      the template for in vitro transcription by the yeast RNA polymerase II (pol II).
      DNase I digestion analysis revealed that transcription of nucleosomes by pol II
      resulted in an overall loosening of the structure. Monitoring the transcription
      event by steady-state fluorescence analysis showed that nucleosomes only
      partially open during transcription. This opening is transient in nature, and
      nucleosomes close back as soon as the pol II falls off the template. Thus, using
      the technique of fluorescence spectroscopy, partial opening of nucleosome
      structure could be differentiated from complete dissociation into free DNA and
      histone octamer, a distinction that may not be possible by techniques like gel
      electrophoresis. Time-resolved fluorescence emission spectroscopy suggested that
      during read-through of the template by the pol II, histone octamers do not fall
      off the DNA. Only minor conformational changes within the histone octamer take
      place to accommodate the transcribing polymerase.

PMID- 8298469
TI  - Idiographic representation of conserved domain of a class II tRNA synthetase of
      unknown structure.

PMID- 8298470
TI  - Is there a place for autologous bone marrow transplantation in chronic myeloid
      leukemia?

PMID- 8298471
TI  - Immunological characterization of the tumor-specific bcr/abl junction of
      Philadelphia chromosome positive chronic myeloid leukemia.
AB  - Recent developments in the understanding of the process of antigen presentation
      by major histocompatibility complex (MHC) molecules and their recognition by T
      lymphocytes has led investigators to speculate that the hybrid bcr/abl fusion
      protein P210 present in chronic myeloid leukemia (CML) cells may generate
      leukemia-specific antigens recognized by T-cells. We used synthetic peptides
      representing the fusion region of P210 to study MHC class I and class II pathways
      of antigen recognition in normal subjects and patients with CML. We found that
      most normal individuals have a low proliferative response to 18mer fusion
      peptides representing the two alternative splicing variants b2a2 and b3a2, and a
      T-lymphocyte precursor frequency (HTLPf) characteristic of unprimed responders.
      No increase in HTLPf was found in CML patients after bone marrow transplantation
      (BMT), suggesting that peptide recognition does not form part of the graft-versus
      leukemia process. In contrast, untransplanted patients with CML had very high
      HTLPf, suggesting an autologous but immunologically ineffective recognition of
      leukemia-specific peptides through HLA class II. Preliminary studies using the T2
      cell line (which expresses HLA class I only in the presence of peptides binding
      to HLA-A2) indicate that nonapeptides spanning the breakpoint of the b2a2 and
      b3a2 variants of P210 do not bind to this particular class I molecule and are
      therefore unlikely to initiate class I mediated lymphocyte responses.

PMID- 8298473
TI  - Autografting for patients with chronic myeloid leukemia--the Hammersmith
      experience.
AB  - The optimal approach for curing patients with chronic myeloid leukemia (CML) in
      chronic phase (CP) is an allogeneic bone marrow transplant (BMT). However, this
      approach is not available to the majority of patients. Autografting, using either
      purged or unpurged bone marrow or peripheral blood stem cells (PBSC), could be
      beneficial for patients who are not eligible for BMT. Between 1984 and 1992, 21
      patients with CML in CP were autografted using unmanipulated PBSC harvested
      either at diagnosis or thereafter. Ten of 21 patients survived at a median of 84
      months following autografting (range: 12-108 months). Eleven patients died, seven
      of blast transformation and four from other causes. The timing of the autograft
      or the harvest does not appear to have a bearing on survival.

PMID- 8298472
TI  - Contrasting effects of rh-MIP-1 alpha and TGF-beta 1 on chronic myeloid leukemia
      progenitors in vitro.
AB  - In chronic myeloid leukemia (CML) an abnormality at the stem cell level results
      in unregulated expansion of myeloid progenitors. The mechanism underlying this
      uncontrolled proliferation remains unclear. An in vitro clonogenic assay which
      detects the human counterpart of the murine colony forming unit (CFU) CFU-A/CFU-S
      day 12 was described in a report of our recent findings. CML bone marrow samples
      were found to proliferate in the CFU-A assay, producing colonies morphologically
      indistinguishable from normal controls. The bcr/abl transcripts were sought in
      the RNA from individual colonies using the polymerase chain reaction (PCR). For
      the five CML samples tested to date, the majority of CFU-A colonies at diagnosis
      or in early chronic phase were found to be bcr/abl positive. For normal controls
      both macrophage inflammatory protein-1 alpha (MIP-1 alpha) and transforming
      growth factor-beta 1 (TGF-beta 1) inhibited the proliferation of CFU-A colonies
      when directly added to the assay. In contrast, CML progenitors responded normally
      to TGF-beta 1, but showed no response to MIP-1 alpha. In suicide assays, for five
      normal bone marrow samples, CFU-A progenitors induced into S-phase returned to a
      quiescent state after treatment with MIP-1 alpha. CML progenitors demonstrated
      inherently high cycle status which showed no definite response to MIP-1 alpha.
      However, TGF-beta 1 resulted in quiescence of CML progenitor cycling. In
      conclusion, the primitive progenitors from CML samples were inhibited normally by
      TGF-beta 1 but showed no response to MIP-1 alpha.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8298474
TI  - Autologous transplantation for chronic myelogenous leukemia with mafosfamide
      treated marrow.
AB  - Ten adult patients with Ph-positive chronic myelogenous leukemia (CML) received
      autologous bone marrow transplantation (ABMT) using marrow treated ex vivo with
      mafosfamide. At the time of ABMT, six patients were in chronic phase and four in
      accelerated phase. Seven of ten patients reported herein were selected on the
      basis of a previous laboratory assessment of the numbers of normal and leukemic
      stroma-adherent progenitor cells within mafosfamide-treated marrow. Only patients
      showing > or = 50% Ph-negative stroma-adherent progenitor cells within
      mafosfamide-treated marrow were considered eligible for autografting. In nine out
      of ten evaluable patients, the median time to achieve 500 neutrophils/microliters
      was 32 days (range: 25-72). A platelet count of 2 x 10(4)/microliters was
      achieved at a median of 40 days (range: 27-97). Six out of nine analyzable
      patients engrafted Ph-negative. The median duration of the Ph-negative
      hematopoiesis, confirmed also by Southern blot analysis, was 6.5 months (range: 4
      30). A good correlation was evident between the results of the in vitro
      preharvest screening test and the in vivo occurrence of normal hematopoiesis post
      transplant. Two patients who showed 75% and 89% Ph-negative stroma-adherent
      progenitors engrafted Ph-positive, whereas four out of five evaluable patients
      who had 100% Ph-negative stroma-adherent progenitors engrafted Ph-negative. After
      a median follow-up of 16 months (range: 3-31), five patients evolved into blast
      crisis, three are alive in hematologic and cytogenetic relapse, and one died
      without evolving into blast crisis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298475
TI  - Investigation of bcr-abl transcription by Ph-positive chronic myeloid leukemia
      progenitors.
AB  - It is now feasible to investigate bcr-abl transcription by the progeny of Ph
      positive (Ph+) early and committed hemopoietic progenitor cells from patients
      with chronic myeloid leukemia (CML). Cells from individual colonies can be
      bisected and each half analyzed by cytogenetics or the reverse transcriptase
      polymerase chain reaction (RT-PCR) method to detect the bcr-abl transcript using
      internal nested oligonucleotide primers that flank the chimeric gene junction. We
      previously showed that some Ph+ colonies have undetectable PCR products for bcr
      abl. When colonies are generated in the presence of alpha interferon (IFN-alpha)
      bcr-abl transcripts are undetectable in the majority of Ph+ colonies. These data
      suggest a potential mechanism for the action of IFN-alpha in Ph+ CML and indicate
      the need for a combined approach with cytogenetics and RT-PCR in analyzing the
      bcr-abl gene.

PMID- 8298477
TI  - Residual Ph-negative stem cells in chronic myeloid leukemia--sometimes or always?
AB  - Some patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia
      (CML) may achieve partially or completely Ph-negative hemopoiesis after treatment
      with high doses of cytotoxic drugs or interferon-alpha at standard dosage. This
      observation leads to three important questions: 1) are Ph-negative myeloid cells
      in such patients strictly normal? 2) can such Ph-negative cells be identified in
      all newly diagnosed patients or only in a minority? and 3) what is the basis for
      the proliferative advantage manifested by CML cells and why might it be
      temporarily lost as a result of treatment? The mechanisms that might prevent the
      proliferation of normal cells in an environment of Ph-positive cells and the
      relevance of these questions to the design of a strategy aimed at obtaining
      complete remission in the majority of patients are considered. Such a strategy
      might incorporate autografting with Ph-negative stem cells harvested during the
      recovery phase of high dose chemotherapy.

PMID- 8298476
TI  - Autografting in chronic myelogenous leukemia followed by immunotherapy.
AB  - Patients with chronic myelogenous leukemia (CML) can be cured with allogeneic
      bone marrow transplantation. Over the past decade, it has become clear that
      immunological mechanisms, in the form of graft-versus-leukemia, constitute an
      integral part of this therapy. Because of limitations imposed by a lack of
      suitable donors, age, and toxicity, only a minority of patients can be offered
      allogeneic bone marrow transplantation (BMT). Recently, attempts have been made
      to employ autologous bone marrow transplantation (ABMT) for the therapy of CML
      using a variety of pre- and post-transplantation manipulations. This report
      describes the rationale for an ongoing clinical trial using the immunomodulator
      roquinimex (Linomide), following autologous bone marrow transplantation, in an
      attempt to stimulate the immunological responses thought to be critical for
      successful therapy in CML.

PMID- 8298478
TI  - Difficulties in collecting peripheral blood stem cells in chronic myeloid
      leukemia related to persistence of the leukemic cell clone.
AB  - Eight chronic myeloid leukemia (CML) patients ineligible for allogeneic bone
      marrow transplantation (BMT) were intensively treated by a myeloablative
      chemotherapy identical to the treatment that we use in acute myeloid leukemia
      (AML). The objectives of such an intensive treatment were both to reduce the size
      of the leukemia stem cell mass as much as possible and subsequently to allow a
      better mobilization of the residual Ph-negative (Ph-) stem cells. Cytogenetic
      analyses were systematically performed on blood-derived stem cells collected at
      the hematopoietic recovery phase following post-chemotherapy aplasia. The length
      of aplasia did not correlate with the evolutive stage of the disease, but was
      negatively correlated with the total colony forming units-granulocyte macrophage
      (CFU-GM) amounts collected. The cytogenetic abnormality remained present in most
      cases in all metaphases counted in leukapheresis products. Three patients were
      transplanted with these leukapheresis products. One died due to sepsis before
      engraftment; the two others engrafted very slowly, while Ph-positive (Ph+) cells
      were found at post-transplant controls. These disappointing results suggest that
      the myeloablative chemotherapy used in this study has not resulted in
      satisfactory advantages for the proliferation of residual normal stem cells over
      the expansion of the Ph+ clone.

PMID- 8298479
TI  - Biological and chemical selection of Ph-negative clones.
AB  - Chronic myelogenous leukemia (CML) is a clonal disorder of the hematopoietic stem
      cell characterized by the co-existence of Philadelphia-negative with Ph-positive
      progenitors. CML progenitor cells have been shown to be defective in adherence to
      marrow stroma. The present study investigated at the cytogenetic level marrow
      derived CML clonogenic cells generated from the stroma-adherent cell fraction.
      Mononuclear marrow cells from CML patients (n = 20) were incubated with
      mafosfamide (100 micrograms/ml) or control medium, seeded onto marrow stromal
      layers, and allowed to adhere (2 h, 37 degrees C). Following a short-term (3
      days) liquid culture, the cells were harvested, incorporated in methylcellulose,
      and individual colonies were analyzed by single colony karyotyping. On direct
      cytogenetic analysis, the overall mean (+/- SD) percentage of Ph-negative
      metaphases was 9 +/- 20%. The mean (+/- SD) percentages of Ph-negative colonies
      grown from the stroma-adherent and the stroma-adherent mafosfamide-treated
      fraction were 41 +/- 32% and 62 +/- 40% (p < or = .005), respectively. Single
      colony transfer experiments revealed that 50 +/- 13% stroma-adherent and 70 +/-
      24% stroma-adherent mafosfamide-treated progenitors gave rise to secondary
      colonies. In conclusion, the present data demonstrate the possibility to select
      Ph-negative clones that: 1) have a maintained capability of stroma adherence; 2)
      are mafosfamide resistant; and 3) have high-replating potential.

PMID- 8298480
TI  - Therapy of chronic myelogenous leukemia.

PMID- 8298481
TI  - Antisense inhibition of P210 bcr-abl in chronic myeloid leukemia.
AB  - The evidence that the bcr-abl gene product (P210) of the Philadelphia chromosome
      plays a crucial role in the pathogenesis of chronic myeloid leukemia (CML), and
      the absence of the bcr-abl fused transcript in non-malignant cells makes this
      messenger RNA an ideal candidate for antisense strategies in CML. To inhibit the
      expression of the bcr-abl gene, and to try to eradicate Philadelphia-positive
      cells, different methods can be used: 1) the introduction into the cells of
      antisense oligonucleotides, 2) the use of specific ribozymes, or 3) the
      transduction, using retroviral vectors, of stably integrated sequences coding for
      antisense RNA. Each of these approaches has potential advantages and drawbacks
      that are discussed below. Although many data emerge that support the use of anti
      bcr-abl antisense molecules in CML, numerous questions remain to be completely
      answered before the most efficient strategy can be designed, either for in vitro
      or in vivo purposes.

PMID- 8298482
TI  - [Contribution of the energy-dependent Ca2+-transport system to smooth muscle
      relaxation].

PMID- 8298483
TI  - [Lipoperoxidase activity of carnosine and carcinine].

PMID- 8298484
TI  - [Computer modeling of structure-forming properties of plus- and minus- DNA
      chains, coding form 5S rRNA and t RNA].

PMID- 8298485
TI  - [Features of the quantum structure of sleep in healthy people and neurotic
      patients].

PMID- 8298486
TI  - [Spatial vision in mammals].

PMID- 8298487
TI  - [A model for establishing the cortical contractility of Xenopus oocytes, based on
      cytoskeletal reorganization].

PMID- 8298488
TI  - [Antigenic activity of synthetic peptides--fragments of viral hepatitis C
      proteins].

PMID- 8298490
TI  - [Regeneration of a specific midgut skin gland after its partial resection in the
      Djungarian hamster (Phodopus campbelli, Rodentia, Mammalia)].

PMID- 8298489
TI  - [The genetic structure of Altayan populations].

PMID- 8298491
TI  - Minute virus of mice-induced modification of the murine DNA polymerase alpha
      primase complex permits the salt-induced dissociation of 12S DNA primase and 10S
      DNA polymerase alpha components.
AB  - DNA polymerase alpha-primase complexes in extracts of MVM-infected murine cells
      were dissociated in the presence of 0.3M KCl to generate a 12S DNA primase and a
      10S DNA polymerase alpha that were readily separated by sedimentation in glycerol
      gradients. A 12S DNA polymerase alpha-primase complex refractory to dissociation
      in 0.3M KCl was identified in extracts of MVM-infected HeLa cells. In extracts of
      mock-infected murine and HeLa cells DNA primase and DNA polymerase alpha were not
      dissociated from each other in 0.3M KCl but remained in a stable complex that
      sedimented at 10S. We propose that a novel 12S DNA polymerase alpha-primase
      complex prone to disruption by salt is induced by MVM infection and that the DNA
      primase component of the complex is modified.

PMID- 8298492
TI  - Guanine nucleotide-binding protein stimulates arachidonic acid metabolism in
      TEA3A1 thymic epithelial cells by stimulating release and inhibiting
      incorporation of arachidonic acid.
AB  - Guanosine 5'-O-(thiotriphosphate) (GTP gamma S), an activator of guanine
      nucleotide binding protein (G protein), increased prostaglandin E2 (PGE2)
      production in saponin permeabilized rat thymic epithelial cells, TEA3A1. Aluminum
      fluoride (A1F4-), a cell permeable G protein activator, also stimulated PGE2
      production and arachidonic acid (AA) release from TEA3A1 cells. Using A1F4-
      instead of GTP gamma S as a G-protein activator, we have investigated the
      mechanism of G-protein mediated stimulation of PGE2 production in TEA3A1 cells.
      Results from our experiments indicate that G protein mediated activation of AA
      metabolism in TEA3A1 cells is regulated by two independent mechanisms. One is by
      the stimulation of AA release via the activation of PLA2 enzymatic activity
      through PLC and PKC mediated pathway and the other is by a concomitant inhibition
      of AA incorporation into membrane phospholipids.

PMID- 8298493
TI  - Inhibition of tyrosine kinase activity abolishes anabolic and mitogenic effects
      of prolactin and growth hormone in Nb2 cells.
AB  - The effect of genistein, a specific tyrosine kinase inhibitor, on intermediate
      and long-term effects of lactogen (growth hormone and prolactin) in Nb2 cells has
      been examined. Genistein inhibited hormone-induced protein and DNA synthesis and
      mitogenesis in a concentration-dependent manner with an IC50 ranging from 10 to
      13 uM. Tyrosine kinase activity was rapidly stimulated by prolactin and was
      completely blocked by 25 uM genistein. These results demonstrate that lactogen
      mediated effects distal to ligand receptor interaction are coupled by tyrosine
      kinase(s) and suggest that this enzyme activity may be critically involved in the
      signal transduction mechanism of lactogens.

PMID- 8298494
TI  - Long-chain acyl-CoA synthetase of rat testis microsomes. Substrate specificity
      and hormonal regulation.
AB  - We investigated long-chain fatty-acyl-CoA synthetase activity in rat testicular
      microsomes. The apparent Michaelis constants (Km's) for the substrate fatty acids
      increased while their corresponding maximal velocities decreased in the order
      18:3(n-3), 20:3(n-6), and 18:0. The reaction with 20:3 as substrate was
      diminished in the presence of a constant amount of either 18:0, 18:2(n-6), or
      18:3(n-3) in a manner consistent with their action as simple competitive
      inhibitors, with the Ki values for 18:0 and 18:3(n-3) being of the same order of
      magnitude as their respective Km's. Adrenocorticotrophin and/or dexamethasone
      administration to intact rats caused a significant decrease in the
      thioesterification of all three substrates without producing any alteration in
      the fatty-acid composition of the microsomal membranes. These results indicate
      the presence of a broad-specificity activating enzyme in testis whose function is
      subject to hormonal regulation.

PMID- 8298495
TI  - Drosophila alcohol dehydrogenase: stereoselective hydrogen transfer from ethanol.
AB  - Drosophila alcohol dehydrogenase shows a broad substrate specificity, with
      secondary alcohols being better substrates than primary alcohols. This
      specificity indicates that the active site contains two hydrophobic interaction
      sites and hence, a primary alcohol should be able to bind in two productive
      modes. This was tested by studying the activity of the enzyme with ethanol, [2H6]
      ethanol and 1S-[2H1]-ethanol. An identical primary kinetic isotope effect of 2.5
      for the two deuterated ethanols showed that deuterium was transferred from the
      enantiomeric 1S-[2H1]-ethanol to the coenzyme. Thus, ethanol interacts with only
      one hydrophobic region of the active site.

PMID- 8298496
TI  - Ageing erythrocytes and alloxan diabetes: I. A possible role of catalase, GSH,
      GSSG, and GSH-enzymes in decreasing defence system.
AB  - The erythrocytes from control (C), diabetic (D) and insulin-treated diabetic
      (D+I) rats were separated into three ageing groups (TAG) i.e., light dense (young
      cells), intermediate-dense (middle-aged cells) and heavy-dense (old aged cells)
      samples. The activities of enzymes and metabolites changed from young to old
      cells in the following manner: (1) Increase of CAT in TAG and a lower level in D
      and D+I (2) Decrease of GPx in TAG but a low level in D (3) Increase of GR in TAG
      but a higher level in D, (4) Increase of GST in C and a decrease in D with a
      higher level in young cells and a lower level in middle-aged and old cells. The
      reversal of enzyme was more in young cells of D+I (5) Increase of GSH in TAG, a
      low level in D and a high level in D+I (6) Increase of GSSG in TAG, a high level
      found only in young cells of D. The results show that young red cells are
      affected more significantly in diabetes than other age cell types.

PMID- 8298497
TI  - Catalytic activity of elastase in reverse micelles.
AB  - The activity of porcine pancreatic elastase has been studied in reverse micelles
      formed by AOT (sodium bis(2-ethylhexyl) sulfosuccinate) in isooctane. For the two
      substrates succinyl-L-Ala-L-Ala-L-Ala-p-nitroanilide and succinyl-L-Ala-L-Ala-L
      Pro-L-Leu-p-nitroanilide, the catalytic constant, kcat, in reverse micelles
      increases with increasing wo until, at high wo, the value of kcat measured in
      bulk buffer solution is approached (wo = [H2O/]AOT]). In analogy to alpha
      chymotrypsin--and in apparent contrast to many other enzymes--elastase does not
      show a maximum in the kcat-wo profile. Within the wo range of 8 to 35, for both
      substrates, the Michaelis constant Km (as expressed relative to the total volume
      of the solution, Km,overall) increases with increasing wo.

PMID- 8298498
TI  - Inhibition of NF-kappa B DNA binding activity by alpha-tocopheryl succinate.
AB  - Vitamin E derivatives have been shown to inhibit tumor necrosis factor-induced NF
      kappa B activation in human Jurkat T cells. The present report demonstrates that
      alpha-tocopheryl succinate directly blocks DNA binding activity of activated NF
      kappa B, as well as the NF-kappa B activation induced by okadaic acid, an
      inhibitor of protein phosphatases 1 and 2A. In contrast, alpha-tocopherol, alpha
      tocopheryl acetate and 2,2,5,7,8-pentamethyl-6-hydroxychromane have no effects.
      These observations suggest that the mechanism of alpha-tocopheryl succinate
      action against NF-kappa B is different from those of other vitamin E derivatives.

PMID- 8298499
TI  - Effect of inorganic phosphate on the self-associating properties of glutathione
      reductase from Spirulina maxima.
AB  - In the presence of millimolar concentrations of inorganic phosphate, native
      Spirulina maxima glutathione reductase (NAD[P]H:GSSG oxidoreductase EC 1.6.4.2.)
      changes its aggregation state. The oligomeric structure of the enzyme was notably
      dependent upon phosphate molarity, ranging from a dimer-tetramer equilibrium at
      relatively low phosphate concentrations into a tetramer-octamer equilibrium at
      moderate or high phosphate concentrations. In spite of the changes in quaternary
      structure, the tetramer remains as the most stable and abundant species. Sodium
      chloride solutions were not able to produce a similar effect, thus discarding an
      unspecific ionic strength effect.

PMID- 8298500
TI  - N-linked glycosylation of the C5a receptor.
AB  - The recent cloning of the cDNA encoding the human C5a receptor reveals a single
      potential site for N-linked glycosylation. Previous studies have suggested the
      presence of at least one carbohydrate moiety in the C5a receptor. Enzymatic
      digestion with Endoglycosidase F confirmed this presence and a point mutation at
      the predicted site of glycosylation was sufficient to lower the apparent
      molecular weight of the receptor as determined by SDS-PAGE. Removal of the
      carbohydrate moiety failed to abolish expression of the receptor and brought
      about only a slight reduction in the dissociation constant of the C5a receptor
      suggesting that the role of glycosylation in the binding of C5a by its receptor
      is limited.

PMID- 8298501
TI  - Very high level overexpression of bacterial elongation factor Tu.
AB  - The tufA gene, which encodes the bacterial elongation factor Tu of E. coli, was
      isolated as a 1226 bp DNA fragment using the polymerase chain reaction(1). EcoR1
      restriction enzyme digestion sites were incorporated at the 3' and 5' termini of
      the gene. The tufA gene was ligated into the plasmid vector pUC19 and was
      sequenced fully. A plasmid shown to contain the tufA gene in the correct
      orientation with respect to the lac promoter of pUC19 was then used to transform
      E.coli strain JM105 and expression of EFTu in induced cultures of the resulting
      clone, JM105 pJBDB01, was measured using a continuous monitoring procedure. The
      clone was shown to produce up to 95 mg of bacterial elongation factor Tu per
      litre of cell culture.

PMID- 8298502
TI  - Effects of some non-steroidal anti-inflammatory drugs (NSAIDS) on steroidogenesis
      in rat and porcine testis.
AB  - Using the rapid gas chromatographic steroid profiling technique, a number of
      metabolites of pregnenolone have been separated and quantified after incubation
      of this steroid with adult rat and neonatal porcine testicular homogenates. It
      was shown that the 5-ene-3 beta-hydroxy- and the 4-en-3-oxosteroid pathways for
      androgen biosynthesis were operating in both species, although the former pathway
      appeared to be more important in porcine testis. This tissue was characterised by
      the formation of several odorous, and pheromonal, 16-androstenes, which were
      quantitatively more important than the androgens. Three non-steroidal anti
      inflammatory drugs (NSAIDS) caused dose-related inhibition of androgen and 16
      androstene biosynthesis when co-incubated with pregnenolone. The order of potency
      was flurbiprofen > indomethacin > > > aspirin. The possibility that the NSAIDS
      may interfere with cytochrome P-450 is discussed, since several steroid
      transforming enzymes, known to be dependent on this cytochrome for their
      activity, were markedly inhibited.

PMID- 8298503
TI  - Characterization of gastric mucosal mucin receptor.
AB  - Mucin receptor was isolated from gastric epithelial cell membrane by a procedure
      involving membrane solubilization with octylglucoside followed by affinity
      chromatography on Sepharose-bound wheat germ agglutinin. The receptor protein
      yielded on SDS-PAGE a single 97kDa band and displayed specific affinity, in a
      concentration-dependent manner, towards the mucin-coated surface. The receptor
      showed requirement for carbohydrate chains in mucin for binding, as their removal
      caused a marked (87%) reduction in binding capacity. Scatchard analysis revealed
      a linear plot with a single class of high affinity binding (Kd = 43.8 nM; Bmax =
      140 pmol/mg protein) sites. The results demonstrate for the first time the
      presence in gastric mucosa of a specific receptor for mucin.

PMID- 8298504
TI  - Purification and characterization of an ATPase inhibitor protein from buffalo
      mitochondria.
AB  - A heat stable, 12kDa protein was purified to homogeneity from buffalo heart
      mitochondria. It suppressed hydrolytic activity of membrane bound mitochondrial
      ATPase and its functional activity was Mg++ and ATP dependent. Maximal inhibition
      was achieved at slightly acidic pH. Its ability to inhibit ATP hydrolysis was
      significantly diminished at alkaline pH and high ionic strength and the purified
      protein had a tendency to aggregate under such conditions. Circular dichroism
      (CD) studies revealed that the protein undergoes reversible changes in secondary
      structure from a predominantly alpha-helical form at alkaline pH to a beta-sheet
      structure at slightly acidic pH. These distinctly different conformations could
      be correlated with functionally 'inactive' and 'active' forms.

PMID- 8298505
TI  - Ferricenium salts instead of dioxygen in glucose oxidase catalysis. A direct
      interaction and analytical implications.
AB  - The ferricenium salt FcH+BF4- behaves as a specific substrate of glucose oxidase
      acting instead of dioxygen with the effective parameters of the Michaelis-Menten
      equation kcat = 2.60 x 10(2) s-1 and KM = 2.7 x 10(-4) M at 25 degrees C, pH 6.8
      and [D-glucose] = 0.001 M. The activity of glucose oxidase can easily be
      monitored by conventional UV-vis spectrophotometry at 617 nm following the
      bleaching of the ferricenium dye.

PMID- 8298506
TI  - Chemical changes during the early phase of in vitro oxidative damage to human
      LDL.
AB  - Much of the oxidative damage to human LDL in vivo may lead to only minimal
      changes in the chemical properties of the LDL. Therefore, chemical changes were
      evaluated during the initial 3 hours of oxidative attack on human LDL with 5
      microM Cu. HPLC analyses were calibrated with a conjugated-diene internal
      standard. Cholesterol-linoleate-hydroperoxide (Chol-18:2-OOH) accumulated much
      more rapidly than alpha-tocopherol was lost. Although large amounts of
      cholesterol arachidonate were destroyed, diene-containing oxidation products of
      this lipid were not identified by HPLC analysis. Phosphatidyl-choline
      hydroperoxides accumulated much more slowly than chol-18:2-OOH. beta-carotene was
      oxidized relatively slowly, but lycopene was destroyed almost as fast as alpha
      tocopherol. The preferential accumulation of chol-18:2-OOH is consistent with a
      model in which alpha-tocopherol is localized to the surface of the LDL particle,
      providing minimal protection to hydrophobic components in the core of the LDL.

PMID- 8298507
TI  - Glucocorticoid receptor binding in proliferating and differentiating cells:
      modulation by a tumour promoting agent.
AB  - The effects of the tumour-promoting agent, phorbol 12-myristate 13-acetate, on
      dexamethasone binding and protein kinase C in proliferating and differentiating
      murine erythroleukemic cells were investigated. Concentration dependent changes
      in steroid binding were observed in proliferating and differentiating cells
      treated with phorbol 12-myristate 13-acetate for 2h or 24h. Ligand binding in
      differentiating cells was consistently lower than in proliferating cells. Reduced
      expression of protein kinase C was observed in differentiating cells as compared
      with proliferating cells; the amount of enzyme protein was reduced on treatment
      of cells with phorbol ester.

PMID- 8298508
TI  - Constrained sequence alignment.
AB  - This paper presents a dynamic programming algorithm for aligning two sequences
      when the alignment is constrained to lie between two arbitrary boundary lines in
      the dynamic programming matrix. For affine gap penalties, the algorithm requires
      only O(F) computations time and O(M+N) space, when F is the area of the feasible
      region and M and N are the sequence lengths. The result extends to concave gap
      penalities, with somewhat increased time and space bounds.

PMID- 8298509
TI  - Yeast--100 years of contribution to biochemistry.
AB  - For centuries mankind has benefited from yeast for its survival as well as for
      joy and even solace in moments of pain. Today the yeast cell is considered a
      universal model yielding answers to important and intriguing questions about cell
      division, differentiation, transduction of signals and cell disorders. Classical
      and molecular genetic methods have been successfully applied to understand the
      association of genes with proteins and functions-a knowledge which has also led
      to the development of new biotechnologies.

PMID- 8298510
TI  - Studies on the utilization of inorganic pyrophosphate by different metabolic
      systems in yeast mitochondria.
AB  - A mitochondrial pyrophosphatase (PPase) from yeast cells (Saccharomyces
      cerevisiae) was studied and characterized. The hydrolytic activity towards
      inorganic pyrophosphate (PPi) was inhibited by different SH-reagents and
      increased in the presence of uncouplers, indicating a possible involvement of
      this enzyme in energy-linked processes. This view was also supported by the
      observation that these mitochondria were able to hydrolyze PPi, generating an
      electrical membrane potential (delta psi) of the same magnitude as that obtained
      with ATP. Both ATP and PPi inhibited the pyruvate dehydrogenase complex and it
      was demonstrated that PPi can be used as substrate by mitochondrial kinases
      leading to the same pattern of protein phosphorylation as when ATP is used.

PMID- 8298511
TI  - ATP and Ca2+ homeostasis in Trypanosoma cruzi.
AB  - Cell viability requires the perfect functioning of the processes controlling ATP
      and Ca2+ homeostasis. It is known that cell death caused by a variety of toxins
      or pathological conditions is associated with disruption of ATP and Ca2+
      homeostasis. Therefore, the study of the mechanisms by which different T. cruzi
      stages regulate the intracellular Ca2+ distribution and the ATP supply to
      maintain cell viability could provide new insights into the physiology of these
      parasites. One important objective of these studies is the identification of
      possible metabolic differences between host and parasite that could be exploited
      for the rational design of new and more effective trypanocidal drugs.

PMID- 8298512
TI  - Interactions of the regulatory ligands Mg2+ and MgATP2- with the renal plasma
      membrane Ca(2+)-ATPase: effects of osmolytes that stabilize or destabilize
      protein structure.
AB  - In this report we analyze the kinetics of activation of the plasma membrane
      Ca(2+)-ATPase from kidney proximal tubules by the regulatory ligands Mg2+ and
      MgATP2-, and we examine modifications in the effects of these ligands that are
      promoted by organic solutes of natural occurrence that stabilize or destabilize
      protein structure and function. The solutes tested were trimethylamine-N-oxide
      (TMA-O), sucrose and urea. TMA-O and sucrose were chosen as representative of the
      different methylamines and polyols, respectively, that accumulate in living
      organisms. The results lead to the conclusion that free Mg2+ and the MgATP2-
      complex both activate the rate-determining E2-->E1 transition during the
      catalytic cycle of the enzyme, by binding to nonidentical and independent
      regulatory sites. They also indicate that TMA-O, sucrose and urea not only
      promote global modifications in the enzyme structure, but also modify specific
      interactions of the ligands Mg2+ and MgATP2- at their regulatory sites.

PMID- 8298513
TI  - The four-way DNA junction: a fluorescence resonance energy transfer study.
AB  - Fluorescence resonance energy transfer (FRET) measurements on four-way DNA
      junctions have been carried out in order to analyze the global structure and its
      dependence on the concentration of several types of ions. The stereochemical
      arrangement of the four DNA helices that make up the four-way junction was
      established by a global comparison of the efficiency of FRET between donor and
      acceptor molecules attached pairwise in all possible permutations to the 5'
      termini of the duplex arms of the four-way structure. The results indicate that
      the four-way junction isomerizes from an unstacked extended square arrangement of
      the four duplex arms at low ion concentration to an antiparallel stacked X
      structure as the salt is added. The ion-related conformational change progresses
      in a continuous non-cooperative manner as the ionic strength of the solution
      increases.

PMID- 8298514
TI  - Serum LH levels in the differential diagnosis of hirsute anovulatory women.
AB  - Polycystic ovarian syndrome (PCO) occurs frequently in hirsute patients. A
      dissociated explosive response of LH to LHRH administration has been associated
      with the diagnosis of PCO. Twenty-four of 58 women seen because of hirsutism were
      found to have ovarian dysfunction based on clinical signs such as anovulation and
      irregular menstrual cycles. Plasma androgen levels were elevated in the patient
      group. The LHRH test (200 micrograms, iv) was applied to the 24 patients and
      compared with 13 normal ovulatory controls. Serum FSH levels before and after the
      LHRH test were normal in all patients. Two patterns of LH response to LHRH
      stimulation were observed: an explosive response in 17 patients (delta LH: 39.4
      +/- 21.8 IU/l, control group: 7.35 +/- 4.4 IU/l, P < 0.01) and a normal response
      in 7 patients (delta LH: 7.53 +/- 2.41 IU/l). There was a significant correlation
      (r = 0.63, P < 0.05) between basal LH levels and LH response to LHRH. Sensitivity
      and specificity calculated for basal LH levels higher than 6.0 IU/l, considering
      the LHRH test as reference, were 58% and 85%, respectively. The positive
      predictive value measuring the possibility of LH higher than 6.0 IU/l to be from
      a patient with PCO (explosive response to LHRH) was 92%. These data suggest that,
      in hirsute anovulatory patients, basal LH levels may be a good predictor in the
      diagnosis of polycystic ovarian syndrome.

PMID- 8298515
TI  - Dietary habits of calcium stone formers.
AB  - 1. Since dietary factors are known to be related to nephrolithiasis, calcium
      stone-forming (CSF) patients were evaluated in terms of calcium, total protein of
      both animal and plant origin, carbohydrate and energy intakes, on the basis of 72
      h dietary records during the week plus 24-h dietary records during the week-end.
      2. The data for 77 calcium stone formers (57 with absorptive hypercalciuria and
      20 with renal hypercalciuria) were compared to those for 29 age-matched healthy
      subjects. The body mass index of the CSF group was higher than that of healthy
      subjects (P < 0.05). Consumption of all nutrients was similar for both groups
      during the week but week-end dietary records for CSF showed higher calcium intake
      (586 +/- 38 vs 438 +/- 82 mg/day, P < 0.05), protein to body weight ratio (1.2 +/
      0.1 vs 1.0 +/- 0.5 g kg-1 day-1, P < 0.05) and animal protein (56 +/- 3 vs 40 +/
      3 g/day, P < 0.05) when compared with healthy subjects. 3. Comparison of
      hypercalciuria subtypes (renal hypercalciuria and absorptive hypercalciuria) did
      not indicate any difference in calcium or energy intake between groups, either
      during the week or during the week-end. However, the absorptive hypercalciuric
      group presented higher protein and animal protein consumption during the week
      end. 4. These data suggest a low calcium intake in this population, even by stone
      formers. The higher animal protein consumption by our calcium stone formers
      observed during week-ends seems to be more important than calcium intake for
      stone formation.

PMID- 8298516
TI  - Effect of a polyunsaturated fatty acid-rich diet on macrophage and lymphocyte
      metabolism of diabetic rats.
AB  - Diabetic subjects present high susceptibility to infections but the mechanisms
      involved are not fully known. Macrophages and lymphocytes utilize glucose and
      glutamine at high rates and these metabolites are important for the function of
      these cells. The present study examines the activities of key metabolic enzymes
      in macrophages and lymphocytes obtained from alloxan-diabetic Wistar rats (10
      weeks old, 7 rats each group). Since the enteral diet was enriched with omega-6
      polyunsaturated fatty acids (PUFA), the effect of these fatty acids was also
      investigated in the same animals. Diabetes caused a marked decrease of hexokinase
      activity (48%; 274.23 +/- 18.43 vs 143.29 +/- 10.35 units for control vs diabetic
      rats) in macrophages and of citrate synthase and glucose-6-phosphate
      dehydrogenase activities (70%; 321.76 +/- 9.18 vs 96.25 +/- 5.43 units for
      citrate synthase and 89.43 +/- 2.33 vs 23.13 +/- 1.09 units for G6PDh for control
      vs diabetic rats) in mesenteric lymph node lymphocytes. A PUFA-rich diet given
      for 6 weeks enhanced hexokinase activities by 30% (274.23 +/- 18.43 vs 342.48 +/-
      15.39, balanced vs PUFA-rich diets for normal and 143.29 +/- 10.35 vs 189.67 +/-
      9.57 for diabetic rats) and reduced citrate synthase activities by 43% (30.31 +/-
      1.73 vs 17.42 +/- 0.95, balanced vs PUFA-rich diets for normal and 29.34 +/- 1.23
      vs 16.73 +/- 1.02 for diabetic rats) in macrophages, and reduced (< 50%; 59.67 +/
      3.45 vs 48.87 +/- 3.37 for hexokinase and 321.76 +/- 2.33 vs 161.66 +/- 9.97 for
      citrate synthase, balanced vs PUFA-rich diets) the activities of both enzymes in
      lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298517
TI  - Inflammatory reaction of rat striated muscle to particles of carbon fiber
      reinforced carbon.
AB  - 1. Carbon fiber reinforced carbon (CFRC) was implanted in rats as particles
      measuring 30 microns or 11 microns, denoted as CFRC-A and CFRC-B, respectively.
      Titanium (Ti) and vitreous carbon (VC) were used as controls. Ti was used with
      the same particle size as CFRC (Ti-A or Ti-B). The VC particles measured 11
      microns. All materials were separately sterilized on ethylene oxide before use.
      2. One hundred and ten female Wistar rats, weighing 180 to 220 g, were divided
      into six groups of 4 to 5 animals each, according the time of the observation (1,
      2, 4, 8, 16 and 52 weeks). 3. Under aseptic conditions, one 3-0 curette full of
      CFRC-A or CFRC-B was implanted into the right triceps surae muscle in each animal
      and the same quantity of Ti-A (paired with CFRC-A) or Ti-B or VC (paired with
      CFRC-B) was implanted into the left muscle. 4. Histological analysis did not show
      necrosis of muscular tissue nor exudative reaction during the acute phase. 5.
      During the chronic phase the particles induced a chronic inflammatory
      infiltration containing fibroblasts, macrophages and giant cells. VC and CFRC-B
      induced the lowest inflammatory infiltration and CFRC-A induced the highest one.
      6. We suggest that the longer carbon fiber fragments contained in CFRC-A may be
      responsible for this more intensive reaction, which may restrict the medical use
      of the preparation.

PMID- 8298518
TI  - Tuberculosis: new strategies for the development of diagnostic tests and
      vaccines.
AB  - New diagnostic tests and vaccines for tuberculosis are being developed by means
      of a strategy based on the study of antigens exclusive to Mycobacterium
      tuberculosis. These antigens were initially identified by Western blots using
      sera from active pulmonary tuberculosis patients against sonic extracts from M.
      tuberculosis and M. bovis BCG. Several proteins present in the M. tuberculosis
      but absent in the Mycobacterium bovis BCG sonic extracts were selected and are
      currently under investigation. One of these, denoted MTP40, has been extensively
      studied. The nucleotide sequence of the mtp40 gene has been obtained;
      hybridization studies have shown that this DNA fragment is exclusive to M.
      tuberculosis. Using this genomic fragment, a polymerase chain reaction (PCR)
      based diagnostic test which allows the specific identification of a minimum of 10
      fg of M. tuberculosis DNA was developed. The diagnostic assay is now being tested
      on uncultured clinical samples in order to determine its usefulness in routine
      diagnosis. Peptides synthesized from the derived sequence for the MTP40 protein
      and also from other M. tuberculosis proteins are now being studied as possible
      candidates for a new generation of synthetic vaccines against tuberculosis.

PMID- 8298519
TI  - Wa idiotype in seropositive rheumatoid arthritis.
AB  - Antibodies against cross-reactive idiotypes (CRIs) may prove useful as phenotypic
      tracers of immunoglobulin variable region genes (VH or VL). CRIs of human
      rheumatoid factors (RFs) seem to be useful in the elucidation of the incidence
      and structural characteristics of the latter. Anti-Wa CRI antibodies were
      produced and an enzyme immunoassay was developed to test polyclonal RFs isolated
      from sera of 20 rheumatoid arthritis (RA) patients, 7 males and 13 females, aged
      17 to 74 years. Seventeen patients had clinically active disease and three were
      in remission. Disease duration ranged from 1 to 25 years and RF titers ranged
      from 1:160 to 1:640. The immunoassay could detect as little as 8 ng of a
      monoclonal purified WaRF and positive results were found in 30% of patient sera.
      Therefore, we may conclude that at least part of the RFs seen in RA patients
      derives from germ line genes.

PMID- 8298520
TI  - Local addition of monosialoganglioside GM1 stimulates peripheral axon
      regeneration in vivo.
AB  - Tubulization repair technique is a useful model to study peripheral nerve
      regeneration by offering quantifiable parameters to assess the possible effect of
      exogenously applied substances on nerve repair. In the present study we
      demonstrated that locally administered GM1 inside a tubular prosthesis at the
      time of implantation can significantly improve the repair process. The sciatic
      nerve of 8 male C57BL/6J mice, approximately 3 months old at the time of surgery
      and divided into two groups of 4 animals each, was transected and the proximal
      and distal nerve stumps were sutured into a polyethylene tube (PT), 0.76 mm
      internal diameter (ID), to bridge a nerve gap of 4 mm. The tubes contained 2
      microliters of collagen type I (2.4 mg/ml) alone or in combination (1:1 volume
      ratio) with monosialoganglioside GM1 (10 mg/ml in the final solution). Four
      additional animals received a PT with 1.14 mm ID filled with 5.5 microliters of
      collagen/GM1 (at the same ratio and final concentration as above). After 6 weeks
      the PT with the regenerating nerve cables were processed for total myelinated
      axon counts with a computer-controlled system. GM1 significantly increased
      peripheral axon regeneration (3427 +/- 64 myelinated axons for the 0.76-mm PT and
      3623 +/- 270 for the 1.14-mm PT, mean +/- SEM) compared to the group receiving
      collagen alone (2516 +/- 156) and this effect did not depend on tube diameter.
      This action is possibly due to a stimulating effect of GM1 on neurite outgrowth
      and sprouting.

PMID- 8298521
TI  - Effects of the 5-HT receptor antagonists cyanopindolol, ICI 169,369, cisapride
      and granisetron on neuroleptic-induced catalepsy in mice.
AB  - Typical neuroleptics (e.g. haloperidol) can induce catalepsy in rodents.
      Selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonists reduce neuroleptic
      induced catalepsy (NIC), suggesting that this subtype of serotonin receptor plays
      a role in the modulation of nigrostriatal dopaminergic transmission. The present
      study was designed to evaluate the participation of other 5-HT receptor subtypes
      in NIC. Adult albino mice (both sexes, 26-35 g) were used. Catalepsy was induced
      with haloperidol (H; 1.5 mg/kg, ip) and measured at 30-min intervals by means of
      a bar test. Cyanopindolol (a 5-HT1B receptor antagonist), ICI 169,369 (a 5-HT1C/2
      receptor antagonist) and granisetron (a 5-HT3 receptor antagonist) were used.
      Buspirone, a 5-HT1A partial antagonist, cisapride, a 5-HT3/5-HT4 ligand and
      clomipramine, a 5-HT neuronal uptake blocker, were also employed. These drugs
      were injected ip, 20 min before H, with each animal (9-10 per group) used only
      once. Cyanopindolol (0.3 mg/kg) or ICI 169,369 (5 mg/kg) did not significantly
      affect NIC (375 +/- 39 and 378 +/- 34 s vs 372 +/- 44 s for controls, at 2 h
      after H). Buspirone (1 mg/kg) reduced, while pretreatments with either
      granisetron (0.5 mg/kg), cisapride (5 mg/kg) or clomipramine (5 mg/kg)
      potentiated the cataleptic effect of H (107 +/- 19, 576 +/- 52, 815 +/- 76 and
      800 +/- 97 s vs 374 +/- 40 s in the control group, at 2 h after H).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8298522
TI  - Protective effects of diltiazem on the mechanical performance of the hypoxic
      myocardium.
AB  - 1. To determine whether diltiazem protects the hypoxic myocardium by reducing
      contractile work, we have compared the effects of diltiazem and quiescence on
      left ventricular (LV) papillary muscle subjected to hypoxia. Papillary muscles
      were obtained from male Charles River CD rats weighing 150-250 g. 2. Four groups
      of muscles were studied: control (N = 6), non-stimulation (N = 10), diltiazem 10(
      4) M (N = 6) and diltiazem 10(-4) M plus non-stimulation (N = 10). 3. Isolated
      rat LV papillary muscles were studied in Krebs-Henseleit solution with a calcium
      concentration of 2.52 mM at 28 degrees C while contracting isometrically at a
      stimulation rate of 0.2 Hz. Resting tension and active isometric tension were
      measured. 4. Both diltiazem and quiescence significantly attenuated contracture
      tension during hypoxia (0.91 +/- 0.10 vs 2.26 +/- 0.49 g/mm2 for diltiazem vs
      control, and 0.55 +/- 0.18 vs 2.26 +/- 0.49 g/mm2 for quiescence vs control).
      Recovery of active tension was improved in the diltiazem groups during
      reoxygenation (4.16 +/- 0.42 vs 3.75 +/- 0.51, 3.53 +/- 0.15 vs 2.90 +/- 0.13,
      5.84 +/- 0.33 vs 6.48 +/- 0.29 and 5.98 +/- 0.90 vs 7.67 +/- 0.68 g/mm2 for
      diltiazem, diltiazem non-stimulation, non-stimulation and control groups). 5. The
      results suggest that the protective effect of diltiazem during hypoxia was due to
      the reduction in energy demand of the myocardium.

PMID- 8298523
TI  - Fasting enhances cell proliferation of gastric epithelium during the suckling
      period in rats.
AB  - The effect of fasting on cell proliferation was studied during the postnatal
      development of the maturing stomach. Metaphase indices were obtained after
      counting mitotic cells blocked by vincristine. The indices were examined at
      different times of day (10:00 a.m. and 6:00 p.m.) in 16 Wistar rats for each age
      (10, 18, 22 and 30 days) with different dietary patterns: only milk; weaning with
      milk and chow; recently weaned, with only chow, and fully weaned, respectively.
      Metaphase indices (mean +/- SEM) for both periods taken together for 10 and 18
      day old animals were significantly higher in fasted (2.25 +/- 0.22% and 2.49 +/-
      0.28%, respectively) than in control fed animals (1.67 +/- 0.09% and 1.84 +/-
      0.05%, respectively), even if not significantly different for one period alone
      (18 h). No significant difference in indices was observed for 22-day old rats
      (fasted = 1.65 +/- 0.28%). The metaphase index of 30-day old rats was
      significantly higher in fed (1.02 +/- 0.16%) than in fasted animals (0.20 +/-
      0.03%). We conclude that fasting enhances cell proliferation in stomach
      epithelium during the milk intake period, in contrast to the inhibitory effect
      observed in adult animals. The weaning period marks a transition to the opposite
      effect of fasting, i.e., a decrease in cell proliferation in 30-day old animals.

PMID- 8298524
TI  - Threshold determination of spreading depression evoking substances in the retina
      in vitro.
AB  - A technique for the determination of the threshold concentrations of chemical
      substances for elicitation of spreading depression is described. The technique
      minimizes the interference of mechanical stimulating effects and alterations in
      the susceptibility of the retina to spreading depression due to changes in
      unstirred layers at the liquid-tissue interphase. The following threshold
      concentrations were shown to elicit the wave: 8000-10000 microM KCl, 100-200
      microM sodium glutamate, 5-10 microM sodium kainate, 10-20 microM sodium N-methyl
      aspartate, 600-1200 microM (NH4)2SO4 and 400-600 microM BaCl2. Variations of K+
      or Mg2+ concentration in the standard Ringer solution that may cause an increase
      or decrease of spreading depression velocity have an inverse effect on the
      threshold for elicitation of the reaction.

PMID- 8298525
TI  - Effect of paraventricular nucleus lesion and cold restraint stress on gastric
      emptying of a liquid meal in rats.
AB  - The effects of cold restraint stress on gastric emptying (GE) and the involvement
      of the hypothalamic paraventricular nucleus (PVN) were investigated in male
      Wistar rats (200-250 g body weight). Electrolytic lesions were produced
      stereotaxically in the nucleus by passing a 2.0-mA current for 10 s through
      stainless steel electrodes. GE was measured by means of a liquid test meal of 5%
      (w/v) glucose solution plus phenol red (6 mg/dl) dye as marker, given by
      orogastric infusion. Cold restraint stress induces a significant increase (43.7%,
      N = 11) in gastric retention of a 5% glucose solution in rats, i.e., a delay in
      GE of this solution. However, restraint stress alone does not produce any change.
      Both truncal vagotomy and electrolytic lesion of the PVN completely block the
      cold restraint-induced delay in GE. However, PVN lesion per se results in a
      decrease of GE (30.6%, N = 10) when compared to nonoperated controls. In
      addition, PVN-lesioned rats exposed to cold restraint present a slightly faster
      GE (14.7%, N = 11) than controls, demonstrating an opposite response to that
      initially observed without lesion. These data suggest an important role for PVN
      efferents, probably influencing medullary vagal preganglionic neurons, in the
      development of this gastric motor impairment under stress conditions.

PMID- 8298526
TI  - The effects of fatty acids on lymphocyte functions.
AB  - 1. Lymphocytes play an important role in cell-mediated immunity and have been
      implicated in inflammatory and autoimmune diseases. 2. Unsaturated fatty acids,
      including oleic, linoleic, alpha-linolenic, arachidonic, eicosapentaenoic and
      docosahexaenoic acids, inhibit mitogen-stimulated lymphocyte proliferation in
      vitro. The inhibition of proliferation is dependent upon the concentration of
      fatty acid, the time during culture of fatty acid addition, the duration of
      exposure of the cells to the fatty acid and the chain length and degree of
      unsaturation of the fatty acid. 3. Unsaturated fatty acids suppress production of
      the immunoregulatory cytokine interleukin-2 by lymphocytes in vitro. 4.
      Triacylglycerols containing unsaturated fatty acids inhibit lymphocyte
      proliferation and natural killer cell activity in vitro. 5. Feeding weanling rats
      diets containing olive oil, evening primrose oil or fish oil results in
      suppression of lymphocyte proliferation. 6. Preliminary studies indicated that
      supplementation of the diet of healthy humans with fish oil-containing capsules
      suppresses lymphocyte proliferation and interleukin-2 production. 7. These
      effects, along with inhibitory effects upon the functions of other cells involved
      in the immune response, in particular monocytes and macrophages, indicate that
      certain unsaturated fatty acid-containing oils (particularly evening primrose oil
      and fish oil) may be of benefit in the treatment of inflammatory and autoimmune
      diseases.

PMID- 8298527
TI  - Molecular analysis of hemophilia B in Brazilian patients.
AB  - 1. The molecular basis of hemophilia B was investigated in 19 Brazilian patients
      from 14 unrelated families. 2. Southern blotting of TaqI-digested DNA samples was
      employed for the screening of gene lesions followed by polymerase chain reaction
      and DNA sequencing for the characterization of mutations. 3. Three different gene
      mutations were characterized: a nonsense mutation at nucleotide 30875 (codon 252,
      CGA-->TGA), a partial deletion comprising exons 1-3 (at least 7.4 kb of
      extension), and a complete deletion (at least 42 kb of extension). These patients
      are now referred to as Ribeirao Preto 1, Ribeirao Preto 2 and Ribeirao Preto 3,
      respectively. 4. The factor IX haplotype (composed of 7 polymorphic sites)
      associated with each mutation was determined. Comparisons with previous studies
      confirmed an independent origin for the nonsense mutation. 5. This study
      represents the first survey of gene lesions associated with hemophilia B in South
      America. The results indicate the presence of heterogeneous mutations, as
      observed in other populations. These results also contribute to the understanding
      of the mechanisms involved in the mutations affecting the FIX gene.

PMID- 8298528
TI  - Prevalence and magnitude of osteopenia in patients with prolactinoma.
AB  - 1. The association between hypogonadism and osteoporosis has been reported. We
      conducted a study to establish the prevalence and magnitude of osteopenia in
      patients with prolactinoma and the relationship of bone loss with the duration of
      hypogonadism. 2. We measured the bone mineral density (BMD) of spine and femur (a
      site that has not been analyzed earlier) in 35 patients with prolactinoma using a
      dual-energy X-ray absorptiometer. The patients were classified as normal BMD and
      low BMD (osteopenics). 3. Seventeen patients (48%) showed osteopenia. The mean
      bone loss in the different regions was: spine, 13%; femoral neck, 15%;
      trochanter, 11%; Ward's, 22%. This difference was only significant when the spine
      and Ward's region were compared. The duration of hypogonadism was significantly
      greater in the low-BMD group (11.3 vs 4.9 years) when compared to the normal BMD
      group. There was a positive relationship between the duration of hypogonadism and
      magnitude of bone loss in both spine and femur (P = 0.04; r = 0.6). 4. A high
      prevalence of osteopenia in both spine and femur was found in patients with
      prolactinoma, and was highly associated with the duration of hypogonadism. Early
      treatment of this condition seems important to prevent bone loss.

PMID- 8298529
TI  - Reduction of urine volume ameliorates adriamycin-induced nephropathy.
AB  - 1. Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular
      lesions in rats, resulting in persistent proteinuria and glomerulosclerosis. 2.
      The effect of urine volume on the progression of adriamycin-induced nephropathy
      was studied in 70 male Wistar rats (180-200 g) observed for 30 weeks and
      separated into 4 groups: healthy control group (HCG, N = 10) inoculated i.v. with
      1 ml of saline, and nephrotic groups inoculated iv with a single dose of
      adriamycin of 3 mg/kg body weight. The nephrotic rats were separated into 3
      groups (N = 20): nephrotic control group (NCG) receiving only adriamycin;
      dehydrated nephrotic group (DNG) water deprived for 36 h within each 48-h period,
      and furosemide nephrotic group (FNG) treated with 12 mg/dl furosemide, and 0.9
      g/dl NaCl in the drinking water. 3. The 30-week survival rates of the DNG (100%)
      and HCG (100%) were significantly higher than those of the NCG (85%) and FNG
      (55%). 4. The proteinuria observed in the HCG (range, 7.38 +/- 0.7 to 13.6 +/-
      1.27 mg/24 h) was significantly lower than that observed for all the nephrotic
      groups throughout the experiment. The DNG presented significantly less
      proteinuria (range, 42.71 +/- 6.83 to 140.10 +/- 19.22 mg/24 h) than the NCG
      (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) from week 10 on. There was no
      significant difference between the mean 24-h proteinuria of the NCG (range, 35.32
      +/- 7.64 to 250.00 +/- 25.91 mg/24 h) and the FNG (range, 35.82 +/- 7.91 to
      221.54 +/- 26.74). 5. The mean frequency of damaged glomeruli was 0.3% +/- 0.3
      for HCG, 42% +/- 6% for CNG, 40.8% +/- 8% for DNG, and 47% +/- 14% for FNG. The
      median value of the tubulointerstitial lesion, evaluated by a semiquantitative
      method, was 0 in HCG, 10 in CNG, 8.5 in DNG and 9.5 in FNG (P < 0.05 for all
      groups compared to HCG). 6. The data indicate that reduction of urine volume has
      a protective effect on adriamycin-induced nephropathy.

PMID- 8298530
TI  - The M-ganglion cell density gradient in New World monkeys.
AB  - The M-ganglion cell distribution was studied in the retinae of New World monkeys,
      the diurnal Cebus and the nocturnal Aotus. Retinal whole mounts were stained by
      the neurofibrillar method of Gros-Schultze. The M-ganglion cell distribution in
      the Cebus and Aotus is similar to that reported for Old World primates, such as
      the Macaca. The M-ganglion cell density peak occurs in the foveal slope and
      declines towards the periphery. There is a nasotemporal asymmetry: in the Cebus
      retina the M-ganglion cell density is 1.2-4.3 times higher in the nasal when
      compared to the temporal region at the equivalent eccentricities; in the Aotus,
      the nasotemporal asymmetry is smaller, 1.6-2.2 higher in the nasal region. We
      compared the M-ganglion cell density with previously published values for the
      density of the total population of ganglion cells and observed a larger
      proportion of M-ganglion cells in the Aotus, when compared with Cebus or Macaca.

PMID- 8298531
TI  - Comparison of anxiety measured in the elevated plus-maze, open-field and social
      interaction tests between spontaneously hypertensive rats and Wistar EPM-1 rats.
AB  - On the basis of open-field and plus-maze results it has been proposed that
      spontaneously hypertensive (SHR) rats are less emotionally reactive than their
      normotensive controls, Wistar-Kyoto (WKY). However, the proposed "anxiolytic
      characteristics" of SHR rats may be questioned in view of the significant
      hypoactivity presented by WKY rats. In the present study, the behavioral response
      of spontaneously hypertensive (SHR) and equally active normotensive Wistar EPM-1
      (EPM-1) rats (4-month old males, 10-13 animals per group) were evaluated in the
      open-field, social interaction and elevated plus-maze tests. In the open-field
      study, no differences were observed for total locomotion frequency and immobility
      duration, but SHR rats presented a higher central square locomotion frequency
      (23.8 +/- 2.1 vs 10.3 +/- 1.6) as compared to EPM-1. SHR rats also exhibited a
      greater duration of social interaction when compared to EPM-1 rats (mean +/- SEM
      values were 113.9 +/- 8.7 s for SHR vs 72.7 +/- 8.6 s for EPM-1 rats after 8-min
      observation). In the elevated plus-maze test, SHR rats presented an increased
      percent of entries (52.8 +/- 3.3 vs 28.3 +/- 4.5) and time in the open arms (65.6
      +/- 6.0 vs 11.1 +/- 1.9) as compared to EPM-1 rats, although the total number of
      arm entries (9.2 +/- 0.9 vs 9.7 +/- 1.0) was unchanged. These results suggest
      that the "anxiolytic behavior" of SHR rats in relation to normotensive controls
      is not related to differences in motility levels.

PMID- 8298532
TI  - Induction of the c-fos proto-oncogene in the rat pineal gland during stress.
AB  - To investigate the effects of stressful stimuli on pineal gland activity, male
      Wistar albino rats (200-250 g, 2-4 per group) were submitted to 30 min of forced
      immobilization or to unilateral vibrissotomy 30 min before sacrifice. In situ
      hybridization was performed with a 35S-labelled 50-base oligonucleotide probe
      complementary to nucleotides 270-319 of rat c-fos on sections containing the
      pineal gland. Autoradiograms were quantified using a JAVA microdensitometer.
      Stressful stimuli induced a significant increase in the expression of c-fos mRNA
      in the pineal gland (restraint = 144.3 +/- 14.4 cpm/mm2; hemivibrissotomy = 206.7
      +/- 29.5 cpm/mm2) as compared to no restraint animals (30.6 +/- 5.1 cpm/mm2),
      animals displaying tonic-clonic seizures after an ip (64 mg/kg) injection of
      pentylenetetrazole (34.0 +/- 4.7 cpm/mm2), or competition (70.6 +/- 11.4 cpm/mm2)
      and RNAase-treated (52.7 +/- 9.1 cpm/mm2) controls. These results raise the
      possibility that stressful stimuli may interfere with pineal gland function.

PMID- 8298533
TI  - Effects of Vibrio cholerae enterotoxin peptide on glomerular filtration rate and
      renal proximal tubular sodium transport.
AB  - Cholera toxin peptide stimulates adenylyl cyclase activity in several tissues and
      causes severe intestinal water and electrolyte secretion. To evaluate the
      regulatory function of sodium transport in renal tubules, we studied the effect
      of cholera toxin peptide on rat kidneys. Isolated kidneys from adult male hooded
      rats weighting 240-335 g were perfused with Krebs-Henseleit solution containing
      60 mg/ml dialyzed bovine serum albumin (BSA). The effects of Vibrio cholerae
      peptide (CT; molecular weight, approximately 82,000 Dalton) on glomerular
      filtration rate (GFR), proximal sodium reabsorption (%pTNa+) and urinary flow
      rate (UF) were studied. All experiments were preceded by a 30-min control period
      and in another group of kidneys the time course of the variables was followed
      without toxin infusion, for a paired control. Control kidneys perfused with Krebs
      Henseleit solution plus 60 mg/ml BSA presented stable GFR (paired internal
      control GFR30 min = 0.596 +/- 0.248 ml g-1 min-1 vs GFR120 min = 0.694 +/- 0.362,
      N = 32; P > 0.05) and %pTNa+ (%pTNa+ 30 min = 75 +/- 8.3 vs 84 +/- 1.6 for the
      internal control, N = 32; P > 0.05). CT caused a dose (0.03, 0.75 and 1.0
      microgram/ml)-dependent decrease in GFR starting at 30 min and with a maximal
      peak of effect at 90 min after toxin infusion (GFRCT = 0.130 +/- 0.086 ml g-1 min
      1, N = 12, vs paired internal control GFRControl/30 min = 0.660 +/- 0.132, N =
      12; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298534
TI  - Cytochrome P450 and glutathione in the liver of rats under exclusive sucrose
      ingestion.
AB  - 1. The objective of the present investigation was to study some of the possible
      mechanisms involved in the protective effect of sucrose ingestion against liver
      necrosis induced by acetaminophen. Three groups of male Wistar rats (220-260 g)
      were submitted to the following experimental conditions for a period of 42 h:
      free access to a balanced commercial diet (Group I), an exclusive sucrose diet
      (Group II) and fasting (Group III). At the end of the experiment, hepatic
      cytochrome P450 levels were measured in 11 rats from each group, plasma
      antipyrine half-life (t1/2) was determined in 40 rats from each group, and
      hepatic glutathione (GSH) concentration in 10 rats from each group. GSH
      consumption elicited by a high dose of acetaminophen (ACP, 1.0 g/kg, by gavage)
      was also determined in 30 rats each from Groups II and III. 2. The liver of Group
      II rats presented a significant reduction of cytochrome P450 levels in the
      microsome fraction (range 0.31-0.46, median, 0.37 nmol/mg vs range 0.60-0.93,
      median 0.74 for group I, and range 0.63-1.22, median 0.91 for group III, reported
      as nmol/mg microsome protein; range 23.8-48.4, median 40.4 vs 66.6-130, median
      81.8 for group I and range 59.0-117.1, median 77.1 for group III, reported as
      nmol/100 g body weight), and a prolongation of antipyrine half-life (146.4 vs
      83.4 min for group I and 93.6 for group III) when compared with the rats of the
      two other groups. 3. Since the toxicity of acetaminophen depends on the
      production of a reactive metabolite by the cytochrome P450 system in the liver,
      we conclude that changes in this system brought about by exclusive sucrose
      ingestion for 42 h may explain the liver protection against the toxicity of a
      high dose of the drug even in the presence of a significant concomitant reduction
      in liver GSH levels.

PMID- 8298535
TI  - Central angiotensin converting enzyme-blockade and thirst.
AB  - 1. The effect of lisinopril, a potent inhibitor of angiotensin converting enzyme
      (ACE), injected into the medial preoptic area (MPOA) on water intake was
      investigated in male Holtzman rats (200-250 g). 2. Injection of lisinopril (2
      micrograms/microliters) into the MPOA abolished the water intake induced by
      subcutaneous (sc) injection of isoprenaline (100%) and water deprivation (90%)
      and drastically reduced the water intake induced by sc injection of
      polyethyleneglycol (60%). A small reduction of water intake induced by lisinopril
      was also observed 90 and 120 min after sc hypertonic saline (N = 10 for each
      group). 3. These results suggest that central ACE activation, particularly in the
      MPOA, plays an important role in the dipsogenic responses induced by the agents
      studied.

PMID- 8298536
TI  - Putting people first: a social constructionist approach to learning disability.
AB  - Moving from an individual to a social focus will allow clinical psychologists
      working with people who have learning disabilities to address a wider range of
      difficulties experienced by this client group. Social constructionist theory may
      be a useful framework to facilitate such an approach, and is intellectually
      compatible with changes occurring in other related disciplines. Research relevant
      to this perspective is reviewed under four subheadings proposed by Doise.
      Implications for clinical practice are discussed by reference to two case
      studies.

PMID- 8298537
TI  - A preliminary study of PTSD and grief among the children of Kuwait following the
      Gulf crisis.
AB  - This preliminary study of Kuwaiti children confirms the significant impact of
      exposure to war atrocities on children. This pilot sampling provided evidence
      that: (1) many children who remained in Kuwait during the occupation had multiple
      war-related exposures; (2) more than 70 per cent of the children reported
      moderate to severe post-traumatic stress reactions; and (3) witnessing death or
      injury and the viewing of explicit graphic images of mutilation on television had
      measurable influence on severity of reaction. The highest mean Child Post
      Traumatic Stress Disorder Reaction Index (CPTSD-RI) score was found for those
      children who reported hurting someone else. Older children had both greater
      exposure to atrocities and higher CPTSD-RI scores. Findings suggest the need for
      public policy to minimize children's exposure to graphic depictions of war
      related injury, death and mutilation.

PMID- 8298538
TI  - Life satisfaction and adjustment of children of alcoholics: the effects of
      parental drinking, family disorganization and survival roles.
AB  - The stress paradigm was used to investigate the extent to which parental alcohol
      dependency, family disorganization ana Black's (1979) and Wegscheider's (1976)
      survival roles affected the adjustment of children of alcoholics (COAs). The
      study was cross-sectional based on the responses of a non-random community sample
      of 112 adolescents. The predictors of life satisfaction differed from the
      predictors of minor psychiatric symptoms. Parental alcohol dependency had no
      direct effect on minor psychiatric symptoms, with low family cohesiveness and
      intimacy being the major determinants of psychopathology. In contrast, parental
      alcohol dependency and family disharmony had an additive effect on level of life
      satisfaction. Family variables did not buffer children from the effects of
      alcohol once they recognized parental drinking as a problem. Nor did the survival
      roles protect children in any way. Indeed, the roles of the 'lost' child, the
      'acting-out' child, and the 'clown' were detrimental to well-being.

PMID- 8298539
TI  - Auditory-verbal hallucinations and the phonological loop: a cognitive
      neuropsychological study.
AB  - A patient with continuous auditory-verbal hallucinations was studied, in
      comparison with two cases with a past history of similar hallucinations, from a
      cognitive neuropsychological perspective. This attempts to place hallucinations
      in the context of a normal cognitive process which has become disordered. The
      process in question is the phonological loop, equivalent to inner speech, derived
      from a model of short-term or working memory. A series of short-term memory
      tests, assumed to rely on the adequate functioning of the phonological loop, was
      administered, the results of which broadly conformed to a normal pattern of
      performance. It is concluded that verbal hallucinations cannot be regarded as
      involving the phonological loop directly. Other points in the short-term
      memory/language system at which verbal hallucinations could arise are discussed,
      as are suggestions for further research of this kind.

PMID- 8298540
TI  - Therapist treatment fidelity in prescriptive vs. exploratory psychotherapy.
AB  - Therapist fidelity to the manuals for prescriptive and exploratory
      psychotherapies was assessed via the Sheffield Psychotherapy Rating Scale.
      Ratings on 220 sessions drawn from the Second Sheffield Psychotherapy Project
      showed adequate inter-rater reliabilities within and between treatments.
      Discriminant analysis showed that the treatments could be differentiated almost
      perfectly even though the same five therapists delivered both of them.
      Relationship enhancing skills, measured by a facilitative conditions scale, were
      held constant across treatments and contributed nothing to the discriminant
      function. There was no evidence that adherence varied with the severity of the
      clients' symptoms and only very limited evidence that it varied with the duration
      of treatment, despite there being adequate statistical power to detect small
      effects. Small variations in adherence with the stage of treatment were found but
      only for sessions of prescriptive therapy.

PMID- 8298541
TI  - Long-term traumatic stress reactions in British Falklands War veterans.
AB  - This brief report summarizes the first available findings on long-term traumatic
      stress syndromes among ex-servicemen who are veterans of the Falklands War. The
      results reveal a correlation between physical injury during the War and post
      traumatic stress disorder, indicating the need for a long-term follow-up survey
      incorporating treatment evaluations and welfare rights.

PMID- 8298542
TI  - Sociotropy, autonomy and personal memories in depression.
AB  - Recent research suggesting an association of sociotropy and autonomy with
      vulnerability to depression in response to different types of event remains to be
      integrated with the cognitive model. This study investigated the relationship of
      sociotropy and autonomy to specific cognitive processes in a sample of 20
      unipolar depressed patients. In the autobiographical memory paradigm used, the
      hypothesis that sociotropy would be associated with faster recall of sociotropic
      negative memories was supported. No support was found for the predicted
      relationship of autonomy with speed of recall of autonomous memories. The
      implications of the results for cognitive vulnerability to specific events are
      discussed and recommendations for replication stressed.

PMID- 8298543
TI  - An analysis of labels for people with learning disabilities.
AB  - There have been many changes in the terminology used to describe people with
      learning disabilities in recent years. One of the arguments for 'new' terms is
      their more positive connotations. This claim was investigated in a study in which
      sixth-form pupils (age 16-19) completed semantic differentials for contemporary
      and older labels referring to learning disabilities. Apart from the label
      'exceptional', all had very similar negative connotations. The problems arising
      from using denotative terms inaccurately in order to foster more positive images
      of individuals with learning disabilities are briefly discussed. Alternative ways
      of deciding between labels are suggested.

PMID- 8298544
TI  - Anticipation of handling the dead: effects of gender and experience.
AB  - In addition to the direct psychological effects of disaster stressors,
      anticipation of stress can itself be debilitating. We examined the relationship
      between the anticipated stress of handling the dead and gender and experience.
      Experienced persons had lower anticipated stress than inexperienced persons.
      Inexperienced, females had higher anticipated stress than inexperienced males;
      experienced males and females did not differ. Results provide support for an
      'inoculation' theory of stress buffering in disaster workers.

PMID- 8298545
TI  - Expectations, experiences and satisfaction with labour.
AB  - Emotional, medical and control aspects of labour were explored in 81 primiparous
      women. Expectations were assessed antenatally and compared with postnatal reports
      of experiences. Expectations of positive emotions were significantly greater than
      experience while negative emotional expectations were paralleled by experience.
      There was a major discrepancy between expectations and experiences of the
      occurrence of interventions, with the proportion of women expecting interventions
      being greatly exceeded by those actually undergoing such experiences. In
      addition, expectations concerning personal control together with the use and
      efficacy of breathing and relaxation exercises in labour were elevated in
      relation to experience. Positive emotional expectations were strong predictors of
      positive emotional experiences and unrelated to negative emotional expectations.
      Expectations in general were positively related to experience but the strength of
      the association was weak. Personal satisfaction (i.e. satisfaction with self) in
      labour was strongly associated with the ability to control panic and other
      aspects of personal control. The ability to control panic was mainly influenced
      by the use of exercises. Attenders and non-attenders at antenatal preparation
      classes showed no significant differences in their experiences or personal
      satisfaction levels. Possible explanations for this absence of impact are
      discussed together with issues concerning the relevance of psychological theory
      to midwifery practice and the need for greater integration.

PMID- 8298546
TI  - Are older adults less compliant with prescribed medication than younger adults?
AB  - To compare compliance in older adults with that of younger people, two studies
      investigated general practice patients taking either a short course of
      antibiotics or long-term medication. These studies examined the effects of age on
      compliance separately from other factors such as memory, domestic conditions,
      health beliefs, numbers of drugs being taken, etc. The results indicate that
      seven variables were independently and significantly related to better
      compliance: accurate knowledge of regimen; belief in the importance of taking
      tablets exactly as prescribed; low resentment of time spent waiting to see the
      doctor; less fear of illness; ability to read the label on the bottle;
      understanding what the doctor has said; and living with a relative. Age as such
      was not a factor affecting compliance. The results are discussed in terms of the
      potential influence of GPs in improving compliance in their patients.

PMID- 8298547
TI  - Anxiety, relaxation and anaesthesia for day-case surgery.
AB  - It is recognized that pre-operative anxiety can have adverse effects on the
      course and outcome of surgery and there is a considerable amount of research into
      the influences of interventions for pre-operative anxiety on a number of post
      operative variables. However, little attention has been paid to the potential
      influences of treatments on intra-operative variables, most notably on the
      facilitation of anaesthesia. The present study examined the impact of a brief
      relaxation procedure on anaesthesia in comparison to attention-control and no
      treatment control procedures. A sample of 21 patients about to undergo
      anaesthesia for day-case surgery were randomly assigned to one of the three
      conditions. It was found that the relaxation treatment significantly reduced pre
      operative anxiety as measured by the state scale of the State-Trait Anxiety
      Inventory (Spielberger, 1983). This reduction was reflected in physiological
      indicators of anxiety. Both the relaxation group and the attention-control group
      required significantly less time to induce anaesthesia and less of the
      anaesthetic agent used to maintain anaesthesia. The relaxation group also scored
      significantly lower than the no-treatment control group on an anaesthetist's
      rating of difficulty of maintenance of anaesthesia. Whilst the relaxation
      treatment appeared to have no advantages over the attention-control procedure in
      terms of anaesthetic requirements, the latter treatment did not reduce anxiety
      and showed no benefit over the no-treatment control condition in terms of an
      anaesthetist's rating of difficulty of maintenance of anaesthesia. In addition,
      following recovery the relaxation subjects reported more favourable perceptions
      of their treatment than the attention-control subjects.

PMID- 8298548
TI  - Steroid prescribing for asthmatics: relationship with Asthma Symptom Checklist
      and Living with Asthma Questionnaire.
AB  - Psychosocial consequences of asthma were assessed for 42 patients attending an
      out-patient clinic using the Asthma Symptom Checklist (ASC), a five-dimensional
      scale of experience during asthma attacks, and the Living with Asthma
      Questionnaire (LWAQ), a unidimensional scale of experience between attacks.
      Although all subscales of the ASC and the LWAQ correlated with the physician's
      prescription of steroids, multiple regression showed that 32 per cent of the
      prescription decision variance was accounted for by two dimensions of the ASC,
      panic-fear and irritability. The LWAQ did not explain additional prescription
      variance, indicating that the physician's decisions were influenced by
      psychological reactions during asthma attacks rather than between attacks.
      Prescription decisions were not influenced by clinic-measured respiratory
      function. The results show some differences with previous studies; implications
      for patient management are discussed.

PMID- 8298549
TI  - Management of male sexual difficulties.

PMID- 8298550
TI  - Alcohol problems.

PMID- 8298551
TI  - Major histocompatibility complex class II molecules, hemopoiesis and the marrow
      microenvironment.
AB  - Currently available data indicate that the earliest identifiable hemopoietic
      progenitor in normal marrow is CD34+ MHC class II-; subsequent expression of MHC
      class II antigens is maturation and lineage dependent. Studies on embryonal cells
      suggest that CD34+DR- cells are actually the common precursors for stromal and
      hemopoietic elements, with the earliest hemopoietic precursor being CD34+DR+. DQ
      antigens are apparently not expressed in cells of hemopoietic potential and the
      expression of DQ appears to be regulated differentially from DR and DP. MHC class
      II antigens are also expressed on some stromal cells, especially those with
      endothelial and macrophage features. MHC class II molecules are involved in
      hemopoietic cell/stroma interaction. The presence of anti-MHC class II monoclonal
      antibodies (MABs) at early stages of stem cell proliferation/differentiation, at
      least under conditions of marrow stress, induces signals which may result in
      final, especially granulocytic, differentiation of later precursors. These may
      interfere with the survival of those cells which are required for long-term
      hemopoietic reconstitution. Observations in allogeneic marrow transplant
      recipients support a role of MHC molecules as expected in allogeneic
      interactions. Results in autologous models point towards a role of MHC class II
      molecules other than that of a histocompatibility marker insofar as these
      molecules or signals transmitted by them appear to be involved in the regulation
      of hemopoiesis.

PMID- 8298552
TI  - Approaches to the treatment of Philadelphia-positive acute lymphoblastic
      leukemia.
AB  - Philadelphia positivity occurs in 20-25% of adult patients with ALL, the
      incidence increasing with age. 'Lymphoid-type' and 'stem cell-type' subgroups
      have been identified. Conventional chemotherapy is ineffective in eradicating the
      disease in the vast majority of patients. Allogeneic BMT is the only treatment
      currently available which offers a reasonable prospect of cure, with a 2 year
      actuarial survival of approximately 40% reported for patients transplanted in
      first remission or after relapse. In the absence of a histocompatible sibling,
      BMT from an unrelated donor early in first remission may be justified in young
      patients with 'lymphoid-type' disease which is characterised by a high rate of
      early relapse. The efficacy of ABMT in unproven; if used, purging should be
      considered as most harvested marrows have molecular evidence of residual disease.
      In the absence of BMT, experimental strategies such as therapy with cytokines to
      enhance differentiation of leukaemic blasts and maintenance interferon early
      after the attainment of CR should be considered.

PMID- 8298553
TI  - Cyclosporine combined with methylprednisolone or methotrexate in prophylaxis of
      moderate to severe acute graft-versus-host disease.
AB  - To evaluate the efficacy of cyclosporine (CYA) regimens in preventing moderate to
      severe acute graft-versus-host disease (GVHD), 25 patients received
      immunosuppressive therapy consisting of either CYA and methylprednisolone or CYA
      and methotrexate (MTX) and the incidence and severity of acute GVHD was compared.
      These patients had leukemia or myelodysplastic syndrome (MDS) and received bone
      marrow transplants (BMT) from genotypically HLA-identical siblings. The incidence
      of grade I-IV acute GVHD in patients on the CYA/methylprednisolone regimen was
      64% (7 of 11) compared with 50% (7 of 14) in those on the CYA/MTX regimen. Five
      of 11 patients with the CYA/methylprednisolone regimen developed moderate to
      severe acute GVHD (grade II-IV), fatal in 3 cases. No patient on the CYA/MTX
      regimen developed moderate to severe acute GVHD. Engraftment was faster in the
      CYA/methylprednisolone group than in the CYA/MTX group. The incidence of toxicity
      observed soon after BMT was comparable between groups. The CYA/MTX regimen may be
      superior to the CYA/methylprednisolone regimen for preventing moderate to severe
      acute GVHD.

PMID- 8298554
TI  - Multivariate analysis of risk factors for survival and relapse in chronic
      granulocytic leukemia following allogeneic marrow transplantation: impact of
      disease related variables (Sokal score).
AB  - Patients with chronic granulocytic leukemia (CGL) can be classified in different
      groups according to risk factors at diagnosis (Sokal). The aim of the present
      study was to assess the impact of Sokal's risk factors in 100 patients with CGL
      undergoing allogeneic BMT. Patients were in first chronic phase (CP) (n = 65), or
      with advanced disease (n = 35), grafted from an HLA-identical sibling following
      conditioning with cyclophosphamide and total body irradiation (TBI). Median
      follow up for survivors is 1783 days (429-3533 days). Variables recorded at
      diagnosis to calculate Sokal's prognostic index were: leukocyte, platelet and
      peripheral blood blast cell counts, age and spleen volume. The median value of
      the Sokal index was 0.87. Projected survival for all patients at 9 years was 28%
      (95% confidence limits (CL) 6-49), 48% (34-62) for first CP patients and 15% (0
      36) for more than first CP patients (p = 0.04). Survival was 25% and 31% for all
      patients with a Sokal index of < 0.87/> or = (p = 0.07) and 55% vs 39% for first
      CP patients only (p = 0.03). The relapse rate was similar for patients with Sokal
      index < 0.87/> or = (41% vs 39%, p = 0.9) and this was also true for first CP
      patients (33% vs 26%, p = 0.8). In multivariate analysis, an interval between
      diagnosis and BMT of > 2 years was the most significant negative predictor for
      survival for the whole group of patients (p = 0.01) and more so for first CP
      patients (p = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298555
TI  - Feasibility and efficacy of maintenance chemotherapy following autologous bone
      marrow transplantation for first remission acute lymphoblastic leukaemia.
AB  - Thirty-eight patients with poor risk ALL in first remission received maintenance
      chemotherapy following ABMT. Patients were conditioned for ABMT with high-dose
      melphalan and single fraction total body irradiation. Maintenance chemotherapy
      was commenced in a total of 26 patients and was tolerated to a median daily dose
      of 6-mercaptopurine of 40.5 mg/m2 and a median weekly dose of MTX 8.3 mg/m2.
      Twenty patients remain alive in first remission with a projected disease-free
      survival of 50% and a median follow-up in survivors of 200 weeks (range 48-387
      weeks). Eleven patients have relapsed at a median of 4.5 months from ABMT. These
      patients were compared with remission patients with ALL receiving conventional
      chemotherapy on the United Kingdom Medical Research Council trials UKALL X and
      XA. After stratifying for major risk factors and allowing for the delay from
      remission to transplant, we have shown a significant reduction in the risk of
      relapse after ABMT (p = 0.04). Disease-free survival was not significantly
      increased due to transplant-related toxicity. This study suggests that
      maintenance chemotherapy to prevent relapse after ABMT for ALL is well tolerated
      and warrants assessment in a formal controlled trial.

PMID- 8298556
TI  - Pulmonary function changes 100 days and one year after bone marrow
      transplantation.
AB  - The pulmonary function of patients receiving autologous or allogeneic bone marrow
      transplantation (BMT) was studied before, 100 days after and 1 year after BMT.
      The 117 patients studied before transplantation showed a slight reduction in
      average total lung capacity (TLC) and transfer coefficient (KCO). These
      reductions were related to haematological disease, previous pulmonary disease or
      irradiation, or use of toxic lung chemotherapy. Studies 100 days after BMT showed
      TLC and KCO decreases of 5% and 8%, respectively. These decreases were related to
      different factors in autologous and allogeneic BMT. The results were influenced
      by previous pulmonary status in autologous BMT patients and the occurrence of
      GVHD in allogeneic BMT patients. Seventy patients underwent pulmonary function
      testing 1 year after BMT. The decrease in TLC values was greater in autologous
      BMT than in allogeneic BMT patients (107 +/- 3% to 100 +/- 3% versus 113 +/- 3%
      to 112 +/- 2%, respectively) although TLC remained normal in both groups. KCO
      values dropped significantly in both populations. Relapse of the initial disease
      was an important factor impairing lung function in the autologous group. TLC and
      KCO changes were strongly related to mortality in both groups. These results
      emphasise the need for frequent pulmonary function tests after BMT to detect and
      quantify lung function changes.

PMID- 8298557
TI  - Role of ultrasonography in the diagnosis and follow-up of hemorrhagic cystitis
      after bone marrow transplantation.
AB  - The role of ultrasonographic examination of the bladder has been retrospectively
      evaluated in 12 patients with hemorrhagic cystitis occurring after BMT. Three
      sonographic patterns of bladder abnormalities have been observed: type 1,
      circumscribed thickening of the wall protruding into the lumen (4 patients); type
      2, diffuse thickening of the wall (3 patients); type 3, intraluminal lobulated
      bulky mass reducing the capacity (5 patients). Sonographic follow-up showed a
      progressive trend of bladder abnormalities: type 3 lesions were always preceded
      by type 1 or type 2 abnormalities. In 10 of 12 patients the cystoscopic findings
      proved the correlation between the sonographic aspects and the progressive stages
      of bladder wall damage. Patients were treated initially by hyperhydration and
      blood products transfusions in order to stop hematuria. The median duration of
      bleeding was significantly longer (p < 0.01) in patients showing type 3 lesions
      (90 days) than in the combined groups with types 1 or 2 lesions (14 days). All 5
      patients with type 3 abnormalities failed treatment and required endoscopic
      removal of clots; hemorrhagic cystitis was the major cause of death in 3 patients
      in this group. Ultrasonography may therefore be considered an accurate
      investigation for assessing the extent of bladder damage and monitoring the
      effectiveness of treatment for this complication.

PMID- 8298558
TI  - Value of routine surveillance cultures for detection of CMV pneumonitis following
      bone marrow transplantation.
AB  - The results of 5018 surveillance cultures for the detection of cytomegalovirus
      (CMV) from 177 patients undergoing allogeneic T cell-depleted bone marrow
      transplantation (BMT) were analysed to determine their value in predicting future
      development of CMV pneumonitis. Twenty-two patients were diagnosed as having CMV
      pneumonitis. The median times of a positive CMV culture result from urine, saliva
      or blood before disease in these patients were 32, 8 and 23 days, respectively.
      The positive predictive value of CMV viraemia for the development of CMV
      pneumonitis was 0.64. Multivariate analysis showed that recipient pretransplant
      CMV seropositivity and increasing recipient age were independent risk factors for
      CMV pneumonitis. By contrast, donor CMV seropositivity was protective against
      disease, supporting the hypothesis that immunity against CMV can be adopted from
      donor T cell-depleted marrow. It is concluded that detection of CMV viraemia in a
      surveillance protocol can predict subsequent CMV pneumonitis but that it is of
      low sensitivity. This might be improved by more frequent sampling or by the use
      of a more sensitive assay, such as the polymerase chain reaction, thus
      identifying individuals who may benefit from 'pre-emptive' therapy.

PMID- 8298559
TI  - Development of tolerance after haplocompatible T-depleted bone marrow
      transplantation.
AB  - We evaluated proliferative responses in mixed lymphocyte cultures (MLC) following
      bone marrow transplantation (BMT) in 14 recipients of T cell-depleted haplo
      compatible parental marrow: 11 for the treatment of severe combined
      immunodeficiency (SCID), 2 for leukemia and 1 for Wiskott-Aldrich syndrome (WAS).
      We compared the results obtained in 9 SCID patients and 1 WAS patient with split
      chimerism (T cells of donor origin, B cells and monocytes of recipient origin) to
      4 patients (2 SCID and 2 leukemias) who were full chimeras (T, B and monocytes of
      donor origin). In the full chimeras, as with the fresh donor PBMC, fresh donor T
      cells did not proliferate in the MLC to recipient non-T cells (E-). In this group
      there were no differences (p > 0.2) between the responses of engrafted T and
      fresh donor T to recipient E- cells. We found tolerance of engrafted donor T
      cells to residual mismatched T cell-depleted (E-) recipient cells in the split
      chimera group. In this group the engrafted T cells had low or no responses in MLC
      to HLA mismatched E- host cells compared with fresh donor cells (p < 0.001). In 3
      of 8 split chimera patients that we tested the addition of small numbers (5000
      10,000) of freshly isolated donor T cells, irradiated or not, resulted in a two
      fold increase in the engrafted T cell response to recipient E- cells. In
      contrast, in 3 of 3 full chimeras tested, the addition of fresh donor T cells had
      no demonstrable effect on the response of engrafted T cells to recipient E
      .(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298560
TI  - Cumulative chemotherapy increases mafosfamide toxicity for normal progenitor
      cells in AML patients: rationale for cryopreserving adapted-dose purged marrow
      early in first complete remission.
AB  - To evaluate whether conditions for adapted dose mafosfamide (mafo) purging vary
      with accumulating chemotherapy, we studied the sensitivity of bone marrow CFU-GM
      in a total of 30 patients at different stages of treatment. We determined the
      dose of 95% CFU-GM growth-inhibition by mafo (ID95) in 23 patients with acute
      myeloid leukemia (AML) and 7 patients with lymphoid malignancies in first or
      second complete remission (CR). Sixteen AML patients were studied in early first
      CR prior to intensive consolidation with high-dose cytarabine (HDAC) and had a
      median ID95 of 130 (range 90-190) micrograms mafo/ml; the median ID95 in 3 of 7
      AML-CR1 and 4 of 7 AML-CR2 patients who previously had HDAC therapy was 75 (range
      55-110) micrograms/ml whereas a control group of 7 patients with lymphoid
      malignancies in CR1 showed a median ID95 of 100 (range 80-160) micrograms/ml. In
      AML the difference between patients in CR1 prior to HDAC and patients in CR1
      after HDAC late consolidation or in CR2 was highly significant (p = 0.0006). We
      conclude that accumulating chemotherapy pre-treatment, in particular HDAC
      intensive consolidation, increases mafo toxicity for non-leukemic bone marrow CFU
      GM and conversely decreases the mafo concentration applicable for adjusted-dose
      purging to eliminate residual leukemic cells. Hence mafo purging appears to be
      more efficient when done in early CR1 compared with later stages of disease.

PMID- 8298561
TI  - Survival of adult bone marrow transplant patients receiving mechanical
      ventilation: a case for restricted use.
AB  - A retrospective study of all adults receiving BMT over a 13 year period at a
      large transplant center was performed to determine overall survival and
      prognostic indicators of poor outcome among patients receiving mechanical
      ventilation (MV). Of 653 adult BMT patients, 191 (29%) received MV after
      transplant. Of these 191, 161 (84%) died on the ventilator or within hours of
      extubation; 18 (10%) survived 1 week after extubation and 6 (3%) survived 6
      months. Survival was not predicted by type of graft, use of total body
      irradiation (TBI) or reason for intubation. The patient's age and the timing of
      intubation were predictive of survival. Of patients > or = 40 years, 98% died
      within a week of extubation and all died within 30 days. Similarly, of those
      intubated within 90 days of transplant, 94% died within a week of extubation and
      all died by day 100. These results suggest that MV is rarely effective in
      achieving long-term survival in adult BMT recipients, especially older patients
      and those early in their transplant course. An argument, based on cost/benefit
      considerations and medical futility, can be developed to withhold MV in certain
      patient subsets apart from a clinical research trial.

PMID- 8298562
TI  - Bone marrow transplantation for chronic myeloid leukemia: long-term results.
      Chronic Leukemia Working Party of the European Group for Bone Marrow
      Transplantation.
AB  - The data on 1480 bone marrow transplants for chronic myeloid leukemia (CML),
      performed between 1979 and 1990 were reported to the registry of the European
      Group for Bone Marrow Transplantation (EBMT). Of these, 1082 patients were
      transplanted in first chronic phase, 88 in subsequent chronic phase, 251 in
      accelerated phase and 59 during blast crisis. For these four disease stages
      leukemia-free survival (LFS) at 5 years is 39%, 22%, 22% and 0%, respectively. A
      more detailed analysis was performed for 947 patients receiving a first
      transplant in first chronic phase of their disease from an HLA-identical sibling
      donor. Survival at 8 years is 47%. At 5 years, relapse incidence (RI) is 33% and
      the transplant-related mortality rate (TRM) is 42%. The major prognostic factors
      are patient age (LFS, TRM), T cell depletion (LFS, RI), time from diagnosis to
      transplant (LFS, TRM), white blood cell count (RI) and donor-recipient sex
      combination (LFS, TRM). This first report on long-term results of a large cohort
      of transplanted CML patients confirms and extends previous findings. Stage of
      disease at time of transplant is the most important prognostic factor. Fifty per
      cent of all patients transplanted for CML in chronic phase can be expected to be
      alive at 8 years post-transplant, 40% alive and free of the disease. This number
      increases to > 60% for patients given cyclosporin and methotrexate without T cell
      depletion as GVHD prophylaxis. However, there is no plateau phase and late
      relapses and late transplant-related deaths occur in all subcategories.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8298563
TI  - Autologous bone marrow transplantation for acute leukemia: results and prognostic
      factors in 90 consecutive patients.
AB  - The results of autologous bone marrow transplantation (ABMT) in acute leukemia
      (AL) and the prognostic factors for outcome were analyzed in a series of 90
      consecutive patients treated at a single institution (mean +/- SD age: 25 +/- 11
      years). Diagnosis was: AML (n = 43), ALL (n = 44), acute undifferentiated
      leukemia (n = 2) and acute bilineage (n = 1). Disease stage at ABMT was: first
      complete remission (CR1) 46 cases, CR2 33, other stages 11. Conditioning
      consisted of cyclophosphamide and total body irradiation in 88 patients. The 3
      year probability of disease-free survival (DFS) was influenced by disease stage
      at ABMT: CR1 48%, CR2 28%, CR3 plus CR4 15%. The characteristics associated with
      a high probability of relapse were: in AML a FAB subtype other than M1 or M3 (p =
      0.01) and in ALL an interval between CR1 and ABMT of < 3 months (p = 0.002). A
      WBC > 15 x 10(9)/l at diagnosis (p = 0.01), splenomegaly at diagnosis (p = 0.002)
      and time to CR1 > 4 weeks (p = 0.06) increased the risk of relapse in the entire
      group in CR1. In multivariate analysis, WBC at diagnosis (p = 0.006) and disease
      stage at ABMT (p = 0.03) independently influenced DFS. This study confirms the
      encouraging results of ABMT in CR1 but further antileukemia measures are
      necessary in patients with adverse prognostic features.

PMID- 8298564
TI  - Dose escalation of mitoxantrone given with thiotepa and autologous bone marrow
      transplantation for metastatic breast cancer.
AB  - High-dose chemotherapy given with autologous bone marrow support has resulted in
      significant tumor responses in the majority of patients with metastatic breast
      cancer, a minority of which are durable. To improve on these results, we are
      developing high-dose preparative regimens which may be given in successive
      cycles, each with autologous bone marrow transplantation (ABMT), over a short
      duration. In this report, 44 patients with metastatic breast cancer were treated
      with thiotepa (total dose: 900 mg/m2) and mitoxantrone (MT), administered in a
      dose-escalation fashion, with ABMT. The dose-limiting non-hematologic toxicity of
      mitoxantrone was cardiotoxicity, with the maximum tolerated dose being 50 mg/m2
      Mucositis and pneumonia were also frequent treatment-related side-effects. The
      overall tumor response rate was 49% in this heavily pre-treated group of
      patients. We are currently evaluating the toxicity and efficacy of tandem non
      cross-resistant transplant regimens, using the MT combination for the second
      cycle of therapy, in patients with metastatic breast cancer sensitive to standard
      dose chemotherapy.

PMID- 8298565
TI  - Combination graft-versus-host disease prophylaxis using immunotoxin (anti-CD5-RTA
      [Xomazyme-CD5]) plus methotrexate and cyclosporine or prednisone after unrelated
      donor marrow transplantation.
AB  - Unrelated donor (URD) bone marrow transplantation (BMT) is associated with more
      frequent and more therapy-resistant graft-versus-host disease (GVHD). We tested
      an in vivo immunotoxin with direct cytolytic potency against CD5-expressing T
      lymphocytes (Xomazyme-CD5) for GVHD prophylaxis after URD BMT. The immunotoxin
      was given in vivo (0.1 mg/kg/day) for 3 weeks following transplantation in
      combination with methotrexate+prednisone (MXP; n = 16) or
      methotrexate+cyclosporine (MCX; n = 6). The 22 patients (10 phenotypically
      matched with their donors and 12 partially matched) received unmanipulated
      marrow. MXP was well tolerated, while MCX led to unacceptable nephrotoxicity,
      weight gain and edema. Four patients died of early complications. Thirteen of 17
      evaluable patients achieved myeloid engraftment by 17-40 days (median 24 days).
      Acute GVHD developed in 9 of 15 evaluable patients (5 grade III/IV). Six of 8
      evaluable patients developed chronic GVHD. Four patients survive 1.1-2 years
      after BMT. Although this immunotoxin has previously shown potency in prophylaxis
      of murine GVHD and therapy of human GVHD, in this trial inadequate
      immunosuppressive potency of the immunotoxin combinations was associated with
      unacceptable clinical toxicity. Aggressive immunoprophylaxis against GVHD is
      required to improve the success of URD BMT.

PMID- 8298566
TI  - Listeria meningitis after bone marrow transplantation.
AB  - Over the past decade infections from food-borne Listeria monocytogenes have
      become an important cause of septicaemia and meningitis and immunocompromised
      patients are at particular risk. We report three cases of Listeria meningitis
      occurring post-BMT. The patients were aged 53, 51 and 56 years and presented 4, 7
      and 90 months post-transplant, respectively. The first patient had undergone
      allogeneic BMT for myelodysplasia and the other two patients had ABMT for AML in
      second and first CR, respectively. All the patients presented with classical
      features of meningitis and L. monocytogenes was cultured from cerebrospinal
      fluid. All made a full recovery with appropriate antibiotic therapy. We have not
      seen cases of meningitis due to other organisms in our transplant programme and
      the cases represent a risk of one episode per 59 surviving patient years. None of
      the patients was receiving prophylactic post-BMT antibiotics and the episodes may
      strengthen the case for using prophylactic penicillin. Recent epidemics of
      septicaemia and meningitis caused by L. monocytogenes-contaminated milk and
      cheese suggest that these patients should be informed about potential sources of
      infection.

PMID- 8298567
TI  - Bone marrow transplantation and lymphocyte subset kinetics.

PMID- 8298568
TI  - A comparative study on protein incorporation of L-[methyl-3H]methionine, L-[1
      14C]leucine and L-2-[18F]fluorotyrosine in tumor bearing mice.
AB  - Brain and tumor uptake of L-[methyl-3H]methionine (3H-Met), L-[1-14C]leucine (14C
      Leu) and L-2-[18F]fluorotyrosine (18F-Tyr) and their incorporation into the acid
      precipitable fraction (APF) were investigated in mice bearing FM3A-P0 and the
      higher metastatic FM3A-P15A mammary carcinomas in order to compare the potential
      of positron emitting analogs for measuring protein synthesis rates (PSR) in brain
      and tumors by positron emission tomography (PET). The total uptake of the 3H-Met
      by the brain was higher than those of two other amino acids. On the other hand,
      the incorporation rates into the APF in the brain and tumors were significantly
      faster with 14C-Leu compared to the others. Most of the 14C in the APF was
      identified in labeled proteins; however, considerable amounts of 3H were
      recovered in the lipid and RNA fractions, and 18F was also detected in the
      lipids. Among the positron emitting analogs of three amino acids, 11C-labeled Leu
      could be the most suitable for measuring PSR by PET. For all the amino acids, the
      total uptake and the APF both expressed as the % injected dose seemed slightly
      higher in the FM3A-P15A than in the FM3A-P0, although the differences did not
      reach statistical significance.

PMID- 8298569
TI  - Autoradiography-based, three-dimensional calculation of dose rate for murine,
      human-tumor xenografts.
AB  - A Fast Fourier Transform method for calculating the three-dimensional dose rate
      distribution for murine, human-tumor xenografts is outlined. The required input
      includes evenly-spaced activity slices which span the tumor. Numerical values in
      these slices are determined by quantitative 125I autoradiography. For the
      absorbed dose-rate calculation, we assume the activity from both 131I- and 90Y
      labeled radiopharmaceuticals would be distributed as is measured with the 125I
      label. Two example cases are presented: an ovarian-carcinoma xenograft with an
      IgG 2ak monoclonal antibody and a neuroblastoma xenograft with meta
      iodobenzylguanidine (MIBG). Considering all the volume elements in a tumor, we
      show, by comparison of histograms and also relative standard deviations, that the
      measured 125I activity and the calculated 131I dose-rate distributions, are
      similarly non-uniform and that they are more non-uniform than the calculated 90Y
      dose-rate distribution. However, the maximum-to-minimum ratio, another measure of
      non-uniformity, decreases by roughly an order of magnitude from one distribution
      to the next in the order given above.

PMID- 8298570
TI  - Liver distribution of 99mTc-DL-homocysteine in experimental hepatitis rats.
AB  - Liver accumulation of 99mTc-DL-homocysteine (99mTc-Hcy), which had been found to
      accumulate in several experimental tumors, was studied using experimental
      hepatitis models of rats. The distribution of this compound in liver of rats
      treated with CCl4 (25-100 microL/100 g body weight) was more than five times
      higher than that of non-treated rats, corresponding to the accumulation of Evans
      Blue, a marker dye for capillary permeability. Furthermore, in vitro experiments
      indicated that the liver accumulation of 99mTc-Hcy was due to some changes in the
      plasma membranes caused by CCl4 administration. These results indicate that
      lesional accumulation of 99mTc-Hcy is due to, at least in part, an enlarged
      capillary permeability similar to the case of malignant tissues reported
      previously.

PMID- 8298571
TI  - Preparation and evaluation of para-[211At]astatobenzoyl labeled anti-renal cell
      carcinoma antibody A6H F(ab')2. In vivo distribution comparison with para
      [125I]iodobenzoyl labeled A6H F(ab')2.
AB  - A preliminary investigation of an 211At labeled anti-renal cell carcinoma
      antibody fragment, A6H F(ab')2, was conducted. In the investigation, A6H F(ab')2
      was labeled by conjugation with N-succinimidyl p-[211At]astatobenzoate, and the
      in vivo biodistribution was evaluated in athymic mice bearing TK-82 renal cell
      carcinoma xenografts. As a control, p-[125I]iodobenzoyl labeled A6H F(ab')2 was
      coinjected with the astatinated F(ab')2. The data obtained demonstrated that the
      two radiolabels (211At and 125I) had quite similar distributions, providing
      evidence that the 211At remained attached to the A6H F(ab')2 in vivo. Further,
      the astatinated antibody attained a 2:1 tumor-to-blood ratio, and greater than
      35:1 tumor-to-muscle ratio, at 4h post-injection, suggesting that this antibody
      conjugate could be used to evaluate treatment of metastatic renal cell carcinoma
      in a mouse model.

PMID- 8298572
TI  - Synthesis of the 123I- and 125I-labeled cholinergic nerve marker (-)-5
      iodobenzovesamicol.
AB  - The highly toxic curraremimetic and cholinergic neuron marker (-)-5
      iodobenzovesamicol (IBVM) has been labeled with iodine-125 and iodine-123.
      [125I]IBVM, suitable for animal distribution and ex vivo autoradiographic
      studies, was synthesized by solid-state exchange; isolated yields were 65-89%
      with specific activities in the range of 130-200 Ci/mmol. The synthesis of no
      carrier-added (-)-5-[125I]IBVM from the corresponding chiral (-)-5-(tri-n
      butyltin) derivative using Na125I was evaluated using the oxidants H2O2,
      peracetic acid and chloramine-T. Both peracetic acid and chloramine-T gave good
      yields (70-95%). However, when Na123I was utilized, acceptable yields of
      [123I]IBVM were obtained only with chloramine-T. Use of the latter oxidant did
      produce 5-chlorobenzovesamicol which was eliminated during HPLC purification.
      After optimization of the reaction parameters, [123I]IBVM in batch sizes of 10-27
      mCi, is routinely obtained with a specific activity of 30-70,000 Ci/mmol,
      radiochemical purity (> 97%) and chiral purity (> 98%). Isolated radiochemical
      yields have averaged 71% (N = 40). Distribution analyses of [125I]IBVM and
      [123I]IBVM in mice 4 h following intravenous administration show essentially
      equivalent concentrations of the two tracers in the four brain regions sampled.
      The exceptionally high specific activity of [123I]IBVM has made possible the
      evaluation of this radiotracer in humans.

PMID- 8298573
TI  - High yield synthesis of high specific activity R-(-)-[11C]epinephrine for routine
      PET studies in humans.
AB  - R-(-)-[11C]Epinephrine ([11C]EPI) has been synthesized from R-(-)-norepinephrine
      by direct methylation with [11C]methyl iodide or [11C]methyl triflate. The total
      synthesis time including HPLC purification was 35-40 min. The radiochemical
      yields (EOB) were 5-10% for [11C]methyl iodide and 15-25% for [11C]methyl
      triflate. Radiochemical purity was > 98%; optical purity determined by radio
      chiral HPLC was > 97%. The [11C]methyl triflate technique produces R-(-)
      [11C]epinephrine in quantities (80-170 mCi) sufficient for multiple positron
      emission tomography studies in humans. The two synthetic methods are generally
      applicable to the production of other N-[11C]methyl phenolamines and N
      [11C]methyl catecholamines.

PMID- 8298574
TI  - [11C]NNC 687 and [11C]NNC 756, dopamine D-1 receptor ligands. Preparation,
      autoradiography and PET investigation in monkey.
AB  - NNC 687 and NNC 756 [(+)-5-(2,3-dihydrobenzofuran-7-yl)-7-hydroxy-3-methyl- 8
      nitro-2,3,4,5-tetrahydro-1H-3-benzazepine and (+)-8-chloro-5-(2,3
      dihydrobenzofuran-7-yl)-7-hydroxy-3-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine]
      are two new potent dopamine D-1 receptor antagonists. [11C]NNC 687 and [11C]NNC
      756 were both prepared by N-methylation of the corresponding desmethyl compounds
      with [11C]methyl iodide. The reactions were performed in acetone with subsequent
      normal-phase semi-preparative HPLC and resulting in 50-60% radiochemical yield
      (from EOB and decay-corrected) with a total synthesis time of 30-35 min and a
      radiochemical purity higher than 99%. The specific radioactivity obtained at time
      of injection was about 1500 Ci/mmol (55 GBq/mumol). Autoradiographic examination
      of [11C]NNC 687 and [11C]NNC 756 binding in post-mortem human brain sections
      showed specific binding in the striatum, a region with high density of dopamine D
      1 receptors. PET examination of the radioligands in a Cynomolgus monkey
      demonstrated accumulation of radioactivity predominantly in the striatum. The
      ratio between radioactivities in the striatum and the cerebellum was about 2 and
      8 for [11C]NNC 687 and [11C]NNC 756 after 60 min. [11C]NNC 756 should have
      potential as PET ligand for examination of central dopamine D-1 receptors in man.

PMID- 8298575
TI  - Evaluation of a new DTPA-derivative chelator: comparative biodistribution and
      imaging studies of 111In-labeled B3 monoclonal antibody in athymic mice bearing
      human epidermoid carcinoma xenografts.
AB  - Biodistribution and imaging characteristics of monoclonal antibody (MAb) B3
      conjugated to either the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA (CHX-B) or 2
      (p-isothiocyanatobenzyl)-6-methyl-DTPA (1B4M) and labeled with 111In, were
      evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. MAb
      B3, is a murine IgG1k reacting with a carbohydrate antigen abundantly expressed
      by most carcinomas. Both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3 showed good tumor
      targeting with peak values observed at 72 h with 27.6 +/- 7.6 and 25.4 +/- 1.7%
      ID/g, respectively (P > 0.05). High tumor-to-organ ratios were also observed and,
      confirmed by the imaging results. In particular, tumor-to-liver ratios increased
      from 5.0 +/- 0.9 at 24 h to 9.2 +/- 2.0 at 168 h for 111In-(CHX-B)-B3 and from
      4.5 +/- 0.6 to 8.9 +/- 3.5 for 111In-(1B4M)-B3. This was mainly the result of low
      liver accumulation of both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3, with only 2.48
      +/- 0.46 and 2.5 +/- 0.9% ID/g at 168 h, respectively (P > 0.05). Our findings
      indicate that either CHX-B or 1B4M can be successfully used for 111In-labeling of
      MAbs and that 111In-B3 may represent a promising radioimmunoimaging agent.

PMID- 8298576
TI  - Scintigraphic potentials of J001X acylated poly-galactoside for imaging
      inflammatory lesions in pigs.
AB  - Although several approaches already exist for the imaging of inflammatory foci,
      new specific strategies providing functional data on the lesions are required to
      determine the extent of the disease and also to assess anti-inflammatory
      treatment. In our study, we investigated the scintigraphic potential of 99mTc
      J001X, an agent developed for the targeting of macrophages. Due to its well
      documented and progressive evolution of lesions, a model of radiation-induced
      inflammation in pigs was chosen. Our results demonstrated the ability of J001X to
      provide images of inflammatory foci with a high contrast. The contribution of
      some specific and non-specific parameters possibly involved in the scintigraphic
      behavior of J001X is discussed.

PMID- 8298577
TI  - Fluorine-18 and carbon-11 labeled amphetamine analogs--synthesis, distribution,
      binding characteristics in mice and rats and a PET study in monkey.
AB  - No-carrier-added (NCA) (+-)-p-[18F]fluoroamphetamine (2a) and (+-)-6-[18F]fluoro
      3,4-methylene-dioxy-amphetamine (2b) were synthesized through a multistep
      synthesis by nucleophilic substitution of the appropriate precursors (p
      nitrobenzaldehyde, 1a and 6-nitropiperonal 1b, respectively) with [18F]fluoride
      followed by condensation with nitroethane and reduction with LAH in 20-30% yield
      (EOB) in a synthesis time of 90-109 min from EOB. NCA (-)-[11C]methamphetamine
      (4a) and (+-)-3,4-methylene-dioxy-N-[11C]methamphetamine (4b) were synthesized by
      methylation of the appropriate desmethyl precursors 3a and 3b with [11C]H3I in 40
      60% yield (EOB) in a synthesis time of 30 min from EOB. Animal studies in mouse
      and rat revealed that the relative tissue uptake of these radiotracers was
      kidneys > lungs > liver > spleen > brain > heart > blood. The uptakes of these
      radiotracers in mouse brain were high and similar at 5 min post-injection
      (approx. 5%/g) but radioactivity then declined rapidly (approx. 1%/g at 60 min
      post-injection). For compounds 2a and 2b, the activity in the femur did not
      increase with time indicating in vivo defluorination may not be the major route
      of metabolism. Monoamine uptake inhibitors (nomifensine, fluoxetine and
      nisoxetine) did not inhibit but enhance the uptake of (-)-[11C]methamphetamine
      (4a) in the rat brain by greater than 50%. A PET study in a Rhesus monkey
      revealed that the uptakes of (-)-[11C]methamphetamine in different brain regions
      were similar and the retention of the radioactivity in these regions remained
      constant throughout the study. Analysis of arterial plasma by HPLC showed that
      50% of radioactivity remained as 4a at 60 min post-injection.

PMID- 8298578
TI  - Early and delayed distribution of N-isopropyl-[123I]-p-iodoamphetamine in
      haemorrhagic and ischaemic brain.
AB  - Single photon emission computed tomography (SPECT) was used to study
      redistribution of N-isopropyl-[123I]-p-iodoamphetamine (IAMP) in 10 patients with
      intracerebral haemorrhage and 7 with ischaemic stroke. Delayed/early IAMP uptake
      ratios (D/E) were calculated for four different cerebral zones: haematoma or
      infarct, perilesional, normal and crossed cerebellar diaschisis areas. Delayed
      uptake was observed in all areas, but there were no significant differences
      between the haematoma and infarct results nor between the lesional and
      perilesional results. Delayed redistribution of IAMP therefore did not seem to be
      associated with neuronal metabolic activity.

PMID- 8298579
TI  - Evaluation of phenylmethanesulfonyl fluoride (PMSF) as a tracer candidate mapping
      acetylcholinesterase in vivo.
AB  - The availability of phenylmethanesulfonyl fluoride (PMSF), an irreversible
      cholinesterase inhibitor, for a tracer mapping acetylcholinesterase (AchE) in
      vivo in brain and other organs was evaluated using [35S]PMSF in mice and rats.
      [35S]PMSF was well taken up into the brain, heart and muscle, and the
      radioactivities were trapped in these organs. Pretreatment with non-labeled PMSF
      decreased 33-40% of the trapped radioactivities in the brain and other organs in
      mice. However, regional distribution of [35S]PMSF in rat brain did not correlate
      well with that of AchE activity, suggesting that the selectivity of PMSF toward
      AchE may be insufficient for use as an in vivo tracer mapping AchE.

PMID- 8298580
TI  - Guidelines for assessment of vaccine coverage in children. Report of the Canadian
      Pediatric Society.

PMID- 8298581
TI  - Characterization of outbreak and vaccine strains of Bordetella pertussis--Quebec.

PMID- 8298582
TI  - Signal transduction pathways: new targets in oncology.
AB  - For many years the main strategies in the development of anticancer drugs were
      focused on killing tumour cells by means of agents which are blockers of
      transcription or translocation. However, it is evident that the currently
      available anticancer drugs, mainly antimetabolites and alkylating agents, cannot
      cure the most common types of cancer in adults. Therefore, totally new approaches
      are necessary in cancer chemotherapy research; one of these is disturbing cell
      signalling pathways involved in growth and malignant transformation. Several
      studies have concentrated on mechanisms of cell growth and differentiation,
      control through growth factor receptors and their ligands, oncogenes, proto
      oncogenes and other membrane-associated signaling mechanisms. This paper
      discusses the potential targets in these signaling pathways for novel anticancer
      drugs.

PMID- 8298583
TI  - Platelet aggregation inhibitors in neurology.
AB  - This literature review reports on secondary prevention of ischaemic stroke. The
      aim of secondary prevention is to protect patients who belong to a risk group
      from the occurrence of brain infarction. Symptomatic patients with a demonstrated
      carotid artery stenosis of 70% and more will most probably benefit from carotid
      endarterectomy if performed by a skilled surgeon in the absence of
      contraindications. Oral anticoagulant drugs play a minor role in the medical
      prevention of brain infarction. Antiplatelet drugs, however, have been in use for
      almost two decades and (meta-)analysis of clinical trials points to
      acetylsalicylic acid as a drug with a modest but certain contribution of about
      15% in the endpoint reduction, even at lower dosages. The addition of
      dipyridamole to classic acetylsalicylic acid dose appears to increase the
      endpoint reduction to 30%. Neither dipyridamole nor sulfinpyrazone as monotherapy
      have been demonstrated to be efficacious in the secondary prevention of ischaemic
      stroke. Ticlopidine seems a promising alternative for acetylsalicylic acid in
      those patients who suffer adverse effects from acetylsalicylic acid. Ticlopidine
      itself, however, has a number of side-effects that limit its application. New
      clinical trials are under way in order to improve the efficacy of drug treatment
      in the secondary prevention of brain infarction.

PMID- 8298584
TI  - Pharmacokinetics of epoetin in haemodialysis patients after subcutaneous
      administration: influence of chronic treatment.
AB  - The purpose of this study was to investigate whether chronic subcutaneous
      administration of epoetin has an influence on its pharmacokinetics in patients
      with chronic renal failure and anaemia. 14 Patients were included in the study.
      The data of 8 patients could be evaluated at the end of the study. All patients
      were on maintenance haemodialysis. The pharmacokinetic profile of epoetin was
      studied directly after the first subcutaneous administration of 60 U/kg body
      weight. Patients were further treated with epoetin to maintain haemoglobin
      concentration between 6.0 and 6.5 mmol/l. After about one year of treatment the
      pharmacokinetic profile was studied again, using the same dosage. Between both
      profiles no significant differences (paired Student's t-test) were found in the
      pharmacokinetic parameters studied: absorption half-life, time to maximum
      concentration, maximum concentration, elimination half-life, area under the curve
      and mean residence time. However, in individual patients large differences may be
      found.

PMID- 8298585
TI  - Fosfomycin trometamol in a single dose versus seven days nitrofurantoin in the
      treatment of acute uncomplicated urinary tract infections in women.
AB  - In general practice acute uncomplicated urinary tract infections in women are
      treated with different courses of antibiotics. In this study the efficacy and
      tolerability of a single dose of 3 g fosfomycin trometamol and the conventional
      treatment with nitrofurantoin 50 mg four times daily for seven days were
      compared. In a randomized, double-blind, double-dummy trial in 31 general
      practices in the Netherlands 231 patients with symptoms of acute dysuria,
      stranguria and/or urinary frequency received treatment. Evaluation was based on
      resolution of symptoms, dipslide results and side-effects at 4, 9 and 42 days
      after starting the treatment. The clinical cure rates and bacteriological cure
      rates were not significantly different between the treatment groups. Side-effects
      were reported at day 4 by 43% of the women receiving single-dose treatment,
      compared with 25% of the women in the seven-day treatment group, a significant
      difference. At day 9 the groups did not significantly differ in the number of
      patients with side-effects. Almost all side-effects were mild and gastro
      intestinal complaints were reported most. Taking into account the convenience of
      taking a single dose we conclude that fosfomycin trometamol is a reasonable
      alternative to 7 days nitrofurantoin 50 mg four times a day in the treatment of
      women with symptoms of acute uncomplicated urinary tract infections in general
      practice.

PMID- 8298586
TI  - Mucuna pruriens: improvement of the biotechnological production of the anti
      Parkinson drug L-dopa by plant cell selection.
AB  - Routinely grown cell suspension cultures of Mucuna pruriens L. (Fabaceae) were
      able to endogenously accumulate the anti-Parkinson drug L-dihydroxyphenylalanine
      (L-dopa) in the range between 0.2 and 2% on a dry weight (DW) basis. The green
      colour that developed in light-exposed cultures, appeared to be a suitable marker
      to select cells with an increased L-dopa biosynthesis and/or phenoloxidase
      activity. For this purpose, saccharose concentrations from 0 to 4% (w/v), and
      light intensities of 1,000 and 2,000 lux, were involved in the selection
      procedure. After 6 months, photomixotrophic callus cultures with a rapid growth
      and a high L-dopa content of 0.9% (DW) were obtained on 2% saccharose and under
      1,000 lux. The cell suspensions, derived from these calli, accumulated up to 6%
      (DW) L-dopa, which was the highest stable content ever measured in cultures of M.
      pruriens. An L-dopa yield of approximately 1.2 g/l was calculated after 6 days of
      growth. In contrast, compared wtih the standard-grown parent cell line, the
      phenoloxidase activity, and consequently the bioconversion capacity as measured
      after entrapment in calcium alginate, of these high-producing cultures was
      approximately threefold lower.

PMID- 8298588
TI  - Pharmacological Meeting. Noordwijkerhout, The Netherlands, 13-14 December 1993.
      Abstracts.

PMID- 8298587
TI  - Effect of glucose 5% solution and bupivacaine hydrochloride on absorption of
      sufentanil citrate in a portable pump reservoir during storage and simulated
      infusion by an epidural catheter.
AB  - The stability of sufentanil (5 micrograms/ml as citrate) in admixtures with
      glucose 5% or bupivacaine hydrochloride (2 mg/ml) in 100 ml polyvinyl chloride
      portable pump reservoirs was investigated during simulated infusion by an
      epidural catheter at 32 degrees C for 48 h and during storage at 4 degrees C and
      32 degrees C for 30 days. During both experiments a small decrease (< 5%) in
      concentration of sufentanil and bupivacaine was observed. No loss of sufentanil
      or bupivacaine could be detected (in both experiments) in the portable pump
      reservoirs when stored at 4 degrees C for 30 days. A significant decrease of
      sufentanil was observed when stored at 32 degrees C after 30 days when diluted
      with glucose (9.2%) or in combination with bupivacaine (8.9%); also, the
      bupivacaine concentration decreased significantly (4.1%). It is concluded that
      sufentanil in portable pump reservoirs can be used under patient conditions at 32
      degrees C for 7 days when diluted with glucose 5% or 3 days in combination with
      bupivacaine hydrochloride.

PMID- 8298589
TI  - Meeting on Pharmaceutical Sciences. Groningen, The Netherlands, 26 November 1993.
      Abstracts.

PMID- 8298590
TI  - Clinical Pharmacological Meeting. Nijmegen, The Netherlands, 8 October 1993.
      Abstracts.

PMID- 8298591
TI  - A long, hard journey.

PMID- 8298592
TI  - Growing old disgracefully new ideas for getting the most out of life. The hen co
      op.

PMID- 8298593
TI  - Debating for care. The level of dependency of patients transferred from hospitals
      to nursing homes has increased dramatically in the past year. But Linda Nazarko
      questions whether nursing homes have the staff or resources to cope.

PMID- 8298594
TI  - Heating systems. Smart heat.

PMID- 8298595
TI  - Saving VAT on building work.

PMID- 8298596
TI  - Mastery of the environment.

PMID- 8298597
TI  - Recreation is not a luxury.

PMID- 8298598
TI  - Mutual support for carers.

PMID- 8298600
TI  - No nursing without us.

PMID- 8298599
TI  - Spreading the word.

PMID- 8298601
TI  - Surviving shingles.

PMID- 8298602
TI  - Growing horns together.

PMID- 8298604
TI  - Hypothermia.

PMID- 8298603
TI  - As I was saying...

PMID- 8298605
TI  - Brain and gut neuropeptides in peripheral blood mononuclear cells.
AB  - Neuropeptides, initially thought to be common features of gut and brain, are only
      synthesized in immune cells and modulate immune functions. The presence and
      possible functions of these peptides in immune cells in both physiological or
      pathological conditions have been investigated in our laboratory in the last
      years. Some of the data obtained are reviewed here, and future developments of
      the field are indicated.

PMID- 8298606
TI  - Effect of CCK and its antagonists on gastric emptying.
AB  - Cholecystokinin (CCK) belongs to the group of substances known as brain-gut
      peptides: it functions both as a neuropeptide and a gut hormone. The peptide and
      its synthetic derivatives (like for instance CCK-8 and the amphibian counterpart
      caerulein) significantly delay emptying of gastric contents in both animals and
      humans. The fact that CCK, in doses mimicking postprandial plasma levels,
      strongly affects emptying rate suggests the peptide to be a physiologic regulator
      of gastric emptying. Unfortunately, clear definition of the role of CCK in the
      physiology of gastric motor activity has long been hampered by the lack of
      specific and potent non-peptide antagonists of CCK-receptors. The availability of
      such compounds has stimulated a broad array of investigations into the
      physiological actions of this hormone and examination of its putative role in
      certain diseases. This paper summarizes the available data concerning the effect
      of CCK and its antagonists on gastric emptying. The use of selective CCK
      antagonists has allowed to establish that the gastric motor effect of the peptide
      is direct and mediated through the stimulation of CCK-A receptors. As a
      consequence, CCK-A antagonism results in acceleration of emptying rate under
      certain experimental and clinical conditions. This peculiar pharmacologic effect
      of CCK-A antagonists, which could be useful in the treatment of functional
      dyspepsia (idiopathic or diabetic), gastroparesis and gastro-esophageal reflux
      disease (where patients often display a delayed emptying rate of solid food)
      needs to be further investigated, in order to fully explore their potential as
      gastrokinetic drugs.

PMID- 8298607
TI  - Involvement of brain CCK in the adaptation of gut motility to digestive status
      and stress: a review.
AB  - Cholecystokinin is involved at both central and peripheral level in the control
      of gut motility. At CNS level, CCK8 appears to play a major role in the
      adaptation of duodeno-jejunal motility to the postprandial state, ie the
      disruption of the migrating motor complex. CCK8 microinjected into the ventro
      medial nucleus of the hypothalamus (VLH) induces a fed-like pattern not
      reproduced by similar administration into the hypothalamus. Furthermore, CCKA
      antagonists such as devazepide injected into the VMH just prior to the meal
      shortens the duration of the postprandial pattern of activity, an effect not
      reproduced by similar injection into the LH. Similarly the colonic motor
      activation observed after feeding is suppressed by devazepide injected into the
      VMH in rats. In addition, icv administration of CCKA but not CCKB receptor
      antagonist prevents meal- and CCK8-induced colonic hyperkinesia in dogs. In rats,
      emotional stress is associated with an increase in colonic motility related to
      the central release of CRF. We have shown that CCK8 injected centrally, at a
      lower dose than that producing an increase in colonic motility, is able to
      prevent stress-induced colonic motor alteration.

PMID- 8298608
TI  - Colonic vasoactive intestinal polypeptide in ulcerative colitis.
AB  - Vasoactive intestinal polypeptide (VIP) is a 28 amino acid peptide which is
      localised in both the central and peripheral nervous system. In the human colon
      VIP is found in all layers and the highest concentrations have been found in the
      myenteric plexus. It is known that VIP has various effects on intestinal
      functions: i) it is a potent stimulant of mucosal water and electrolyte
      secretion; ii) it is involved in the peristaltic reflex; and iii) plays an
      inhibitory role on immune cell function. Based on these biological effects it has
      been hypothesized that the intestinal mucosal immune system and inflammation may
      be influenced by alterations in the tissue concentrations of VIP. Some authors
      have demonstrated no changes in the VIP colonic content of patients with
      ulcerative colitis, whereas others have demonstrated a reduction. Our results,
      using specific radioimmunoassay, showed that there is a significant decrease of
      VIP in both rectal and colonic mucosa of patients with ulcerative colitis as
      compared to controls. The VIP decrease is selective since substance P and
      calcitonin gene-related peptide were unchanged in the mucosal tissue of
      ulcerative colitis patients and furthermore the VIP alteration is correlated to
      the degree of mucosal inflammation. These findings suggest that the reduction of
      VIP mucosal content, even if it represents a non-specific event, could influence
      local inflammatory response and the activity of the disease.

PMID- 8298609
TI  - A new gastric juice peptide, BPC. An overview of the stomach-stress
      organoprotection hypothesis and beneficial effects of BPC.
AB  - The possibility that the stomach, affected by general stress, might initiate a
      counter-response has not until recently been considered in theories of stress. We
      suggest that the stomach, as the most sensitive part of the gastrointestinal
      tract and the largest neuroendocrine organ in the body, is crucial for the
      initiation of a full stress response against all noxious stress pathology. The
      end result would be a strong protection of all organs invaded by 'stress'.
      Consistent with this assumption, this coping response is best explained in terms
      of 'organoprotection'. Endogenous organoprotectors (eg prostaglandins,
      somatostatin, dopamine) are proposed as mediators. Such an endogenous
      counteraction could even be afforded by their suitable application. A new gastric
      juice peptide, M(r) 40,000, named BPC, was recently isolated. Herein, a 15 amino
      acid fragment (BPC 157), thought to be essential for its activity, has been fully
      characterized and investigated. As has been demonstrated for many
      organoprotective agents using different models of various tissue lesions, despite
      the poorly understood final mechanism, practically all organ systems appear to
      benefit from BPC activity. These effects have been achieved in many species using
      very low dosages (mostly microgram and ng/kg range) after ip, ig, and
      intramucosal (local) application. The effect was apparent already after one
      application. Long lasting activity was also demonstrated. BPC was highly
      effective when applied simultaneously with noxious agents or in already
      pathological, as well as chronical, conditions. Therefore, it seems that BPC
      treatment does not share any of the so far known limitations for 'conventional
      organoprotectors'. No influence on different basal parameters and no toxicity
      were observed. These findings provide a breakthrough in stress theory. BPC, as a
      possible endogenous free radical scavenger and organoprotection mediator, could
      be a useful prototype of a new class of drugs, organoprotective agents.

PMID- 8298610
TI  - Vagal nerve and the gastric mucosal defense.
AB  - An essential role for an intact vagal nerve has been proven in the development of
      gastric mucosal cyto- and general protection. On the other hand, chemically
      induced (ethanol, HCl, indomethacin) gastric mucosal damage is enhanced after
      acute surgical vagotomy. The aims of this paper were to study the possible
      mechanisms of the vagal nerve in the development of gastric mucosal defense. The
      following questions were addressed: 1) effect of surgical vagotomy on the
      development of ethanol- (ETOH), HCl-, and indomethacin (IND)-induced gastric
      mucosal damage: 2) changes in the gastric mucosal defense by scavengers,
      prostacyclin and other compounds (small doses of atropine and cimetidine; 3)
      changes in the gastric mucosal vascular permeability due to chemicals; 4) effect
      of indomethacin in the ETOH and HCl models with and without surgical vagotomy; 5)
      changes in the gastric mucosal content of prostacyclin and PGE2 in the ETOH and
      HCl models after surgical vagotomy; and 6) changes in the role of SH-groups in
      gastric mucosal defense after surgical vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298611
TI  - Gastric lesion development in normal and pylorus ligated rats after cervical
      vagotomy.
AB  - The main purpose of this study was to further investigate the effects of vagotomy
      on gastric lesion development. In contrast to the usual subdiaphragmal vagotomy,
      a different vagotomy at the level of the trigonum caroticum was used both alone
      and in combination with pylorus ligation (done immediately after vagal
      transection). The animals were killed 15 min, 30 min, 1 h and 6 h following
      vagotomy. No damaging effects of sham-vagotomy, or obvious negative effects of
      cervical vagotomy were noted. Prominent lesions appeared after 1 h in rats
      subjected to cervical vagotomy and significantly increased lesions in the early
      period of pylorus ligation were noted. No further aggravation in pylorus ligated
      rats (even an apparent amelioration at 1-h interval) and no lesions in rats with
      cervical vagotomy in the latter period could be explained in terms of a lack of
      reactivity due to exhaustion preceding fatal outcome. Consistent with this, the
      rats subjected to cervical vagotomy died shortly after the 6-h period.

PMID- 8298612
TI  - Changes of gastric mucosal biochemistry in ethanol-treated rats with and without
      acute surgical vagotomy.
AB  - The biochemical background of ethanol-(ETOH) induced gastric mucosal damage was
      studied in rats with intact vagus and after acute surgical vagotomy. Observations
      were carried out on Sprague-Dawley (CFY) strain rats of both sexes. Gastric
      mucosal lesions were produced by intragastric administration of 1 ml 96% ethanol.
      Bilateral truncal surgical vagotomy was carried out 30 min before ETOH
      administration. The number and severity of gastric mucosal lesions was noted 1 h
      after ETOH administration. Biochemical measurements (gastric mucosal level of
      ATP, ADP, AMP, cAMP and lactate) were carried out from the total homogenized
      gastric mucosa. The adenylate pool (ATP + ADP + AMP), energy charge ((ATP + 0.5
      ADP)/(ATP + ADP + AMP)) and ratio of ATP/ADP were calculated. It was found that:
      1) ATP transformation into ADP increased, while ATP transformation in cAMP
      decreased in ethanol-treated animals with intact vagus nerve, while these
      transformations were quite the opposite in vagotomized animals: 2) no significant
      changes were found in the tissue level of lactate: and 3) the extent of
      biochemical changes was significantly less after surgical vagotomy. It is
      concluded that an intact vagus is basically necessary for the metabolic
      adaptation of gastric mucosa.

PMID- 8298613
TI  - Review: principles of physics relevant to the lithotripter.

PMID- 8298614
TI  - Stone geometry and structure dependence on extracorporeal shock wave lithotripsy.
AB  - The in vitro fragmentation effects of electromagnetic-induced shock wave
      lithotripsy (Siemens Lithostar) were studied on parallel laminated schists in
      relation to the incoming shock wave energy and the incoming angle of the incident
      shock wave. Well above the threshold energy, the total amount of acoustic energy
      required for fragmentation remained unchanged regardless of the power setting of
      the high-tension supply. The amount of energy transmitted to the stone was
      limited by a total reflection angle, restricting the available transmission
      surface. These observations determine the effect of shock waves on calculi with
      an irregular shape such as staghorn stones. Lithotripsy-induced cavitation has
      been recognized, but no immediate influence on disintegration has become apparent
      until now.

PMID- 8298615
TI  - In vitro studies of shock wave lithotripsy effects: requirements of model
      systems.

PMID- 8298616
TI  - Effects of high-energy shock waves on rapidly proliferating cells: African clawed
      toad (Xenopus laevis) zygote model.
AB  - To date few studies have described the effects of high-energy shock waves (HESW)
      on benign, rapidly proliferating cells. In the African clawed toad (Xenopus
      laevis) model, previously described in vitro fertilization methods were used to
      study the effects of HESW on zygote cleavage and blastocytosis. Groups of 50
      freshly fertilized ova were placed at the bottom of clear ultracentrifuge tubes
      filled with 5% DeBoers solution, positioned at the f2 focus utilizing the
      biprismatically split halogen red laser of a Dornier XL-1 experimental
      lithotripter, and treated using an 80-nF capacitor at various kilovoltages and
      shock wave (SW) numbers. Controls were treated in an identical fashion but kept
      outside the f2 focus. Cell lysis was the most notable finding at power settings
      in the standard treatment range (12 kV or greater). Increasing kilovoltage at a
      constant SW number (100) correlated linearly with the number of zygotes lysed in
      each group. There was an apparent logarithmic decrease in progression to cleavage
      and early development with increasing kilovoltage. At 10 kV, no effect on
      development was observed. Increasing SW numbers at a constant 19 kV correlated
      linearly with an increase in the number of lysed zygotes in each group.
      Increasing the SW number at constant kilovoltage correlated with an apparent
      logarithmic decrease in progression to cleavage and early development. This
      effect was observed with as few as 10 SW. These experiments have demonstrated a
      correlation between viability and lysis of zygotes with increasing treatment
      energies. The data suggest a threshold setting that minimally affects cellular
      activity (10 kV).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298617
TI  - Review: in vivo effects of extracorporeal shock wave lithotripsy: animal studies.

PMID- 8298618
TI  - Effects of high-energy shock waves on testes of Wistar rats.
AB  - The effects of high-energy shock wave (HESW) on testes are still unknown. We
      investigated Wistar rats at 3 months of age for morphologic and functional
      changes in the testes and in serum follicle-stimulating hormone (FSH),
      progesterone (Prog), and testosterone (T). In an initial study, 12 rats received
      1000 shocks at 19 kV directed at their testes using the JDPN-IV lithotripter. Two
      animals were sacrificed, and their testes were step-sectioned for light and
      electron microscopic examination on the operation day and on postoperation days
      one, two, four, eight, and sixty. There was angiectasis and congestion (58%) and
      focal hemorrhage (42%) in the testicular tissue, as well as mitochondrial
      swelling, reduction or disappearance of mitochondrial cristae (42%), and
      degranulation of the rough endoplasmic reticulum (33%) in spermatocytes. In the
      definitive study, groups of 10 rats were exposed to the same power index directed
      at their testes. One week after this exposure in Group 1 and at 3 and 6 weeks in
      Group 2, the animals were allowed to mate (one male paired with two females).
      There was no statistically significant difference in pregnancy rate or fetal
      number and weight in the female rats mated with the two groups of treated males
      at 3 weeks' gestation or in serum FSH, Prog, and T, or compared with the control
      group. Although there were temporary histologic changes in testicular tissue, the
      rat testes appeared to be functionally resistant to the shock wave energy levels
      used in this experiment.

PMID- 8298619
TI  - Review: urolithiasis--electrohydraulic and laser lithotripsy.

PMID- 8298620
TI  - Review: tissue effects of laser energy.
AB  - The tissue effects of a laser are responsible for the therapeutic value as well
      as the potential for complications. Within certain constraints, the type and
      depth of energy effect can be controlled by the selection of the wavelength as
      well as of appropriate energy parameters. In a clinical endoscopic setting,
      however, precise prediction of tissue penetration is not feasible, and proper use
      relies on the experience and knowledge of the operating surgeon. Considering
      this, it is important for surgeons to understand laser tissue effects and the
      various parameters that influence them.

PMID- 8298621
TI  - Efficacy of in vitro stone fragmentation by extracorporeal, electrohydraulic, and
      pulsed-dye laser lithotripsy.
AB  - Fragmentation has become the standard therapy for urinary calculi in the modern
      era. Stone fragility as well as position and size are important for the
      determination of a treatment program. To compare the efficacy of stone
      fragmentation, seven kinds of human urinary calculi with known composition
      (calcium oxalate monohydrate and dihydrate, dibasic calcium phosphate, uric acid,
      struvite, calcium phosphate, and cystine) were treated by three fragmentation
      techniques commonly used, namely extracorporeal shock wave (SWL),
      electrohydraulic (EHL), and pulsed-dye laser lithotripsy. Uric acid, calcium
      oxalate dihydrate, and calcium phosphate stones could be destroyed easily by any
      of these methods. Struvite was soft but sticky and not easy to break into tiny
      particles. Both dibasic calcium phosphate and calcium oxalate monohydrate stones
      were resistant to the laser and EHL; SWL is the treatment of choice. For cystine
      stones, none of the treatments was satisfactory; SWL was the only way to break
      them into large pieces.

PMID- 8298622
TI  - Review: obstructive uropathy--renal effects and endosurgical relief.

PMID- 8298623
TI  - Effect of internal ureteral stenting of normal ureter on the upper urinary tract:
      an experimental study.
AB  - The effects of internal stenting of a normal ureter on the upper urinary tract
      were studied in 34 male rabbits by plain films, intravenous urograms, and 99mTc
      DTPA renography at weekly intervals. Moreover, pressure-flow studies of the upper
      urinary tract were performed, and urine specimens for culture were obtained
      preoperatively and at the time of sacrifice. Histopathologic examination of the
      kidney, ureter, and ureterovesical junction was performed after animal sacrifice.
      Hydroureteronephrosis and stasis with equivocal obstruction were noted after 1
      week of stenting. These changes were reversible after stent removal. Prolonged
      stenting (> 3 weeks) produced moderate to severe hydroureteronephrosis, and renal
      function was lost in 2 of 18 renal units because of severe hydronephrosis or
      infection. Ureteral stenting did not produce obstruction at a flow rate as high
      as 8 ml/minute. Histopathologic examination showed dilation of the pelvicaliceal
      system and renal tubules, infiltration of the kidney and the ureter with
      inflammatory cells, mucosal ulceration, and muscular hypertrophy of the ureters.
      The bladder mucosa showed a severe inflammatory reaction, Brunn nests, and
      ulceration with occasional metaplasia. Stenting of normal ureters in rabbits
      produced no harmful effects on the kidney if the stents were removed within 1
      week, but prolonged stenting could affect renal and ureteral integrity.

PMID- 8298624
TI  - Management of ureteral strictures by different modalities and effect of stents on
      upper tract drainage.
AB  - Ureteral strictures were induced experimentally by unilateral partial ligation of
      the upper ureter on the left side in 56 female rabbits. Six weeks later,
      stricture stability was documented by intravenous urography. In all cases, there
      was fibrosis of the muscular wall of the ureter. The lumen, although narrowed to
      various degrees, was preserved in most animals, and moderate to marked
      hydronephrosis resulted. Control animals were not treated in order to study the
      natural progress of the stricture. The other strictures were treated either by
      dilation (catheter or balloon) with or without ureteral stenting, by intubated
      external ureterotomy, or by excision of the strictured segment and stented end-to
      end anastomosis. Follow-up studies consisted of intravenous urography,
      renography, and histologic examination for 24 weeks. Ureteral dilation without
      and with 2 weeks of stenting could be an adequate treatment of strictures
      associated with a moderate degree of hydronephrosis. Intubated external
      ureterotomy did not give satisfactory results in any animal. Excision of the
      strictured segment with a stented anastomosis produced satisfactory results and
      has a great role in the treatment of the strictured ureter in comparison with the
      variable outcome of endourologic treatment. Stenting of the unobstructed ureter,
      tested in six rabbits, showed a positive correlation between renal obstruction
      and long-term ureteral stenting.

PMID- 8298625
TI  - Urothelial substitutes: ureter.

PMID- 8298626
TI  - Urothelial substitutes: bladder.

PMID- 8298627
TI  - Visual fields with protective eyewear.
AB  - Sports-related eye injuries are quite common, yet the number of athletes who
      utilize protective eyewear is extremely low. The purpose of this study was to
      determine if there is a significant visual field loss associated with wearing eye
      protection. One of the authors was subjected to standard kinetic visual field
      testing with and without eye goggles. No significant difference was revealed.
      Physicians, physical therapists, and trainers should promote the use of
      protective eyewear and reassure athletes that they will not lose visual field.

PMID- 8298628
TI  - Postarthroscopy physical therapy management of a patient with temporomandibular
      joint dysfunction.
AB  - Arthroscopy of the temporomandibular joint (TMJ) is a new, relatively noninvasive
      surgical procedure for treating patients with TMJ dysfunction beyond nonsurgical
      management. The purpose of this commentary is to introduce a four-stage
      rehabilitation protocol currently used by the authors in the physical therapy
      management of a postarthroscopy TMJ patient with a diagnosis of bilateral
      capsular impingement and adhesions. The patient underwent diagnostic TMJ
      arthroscopy and the four-stage rehabilitation protocol. Stage I exercises to
      maintain mandibular mobility began in the recovery room. Stage II exercises
      consisted of hands-on and take-home stretching exercises. Stage III and IV
      exercises were completed to improve muscular function. The patient was discharged
      from physical therapy in a month with full range of motion and diminished pain
      and headaches. At 1-year follow-up, the patient demonstrated full range of motion
      without pain, further treatment, or medications.

PMID- 8298629
TI  - Frozen shoulder syndrome: a review of literature.
AB  - Physical therapists in a variety of settings treat individuals with frozen
      shoulder syndrome. Frozen shoulder syndrome is a condition in which a soft tissue
      glenohumeral capsular lesion is accompanied by painful and restricted active and
      passive shoulder motion. Despite its common occurrence, there is a significant
      knowledge void concerning frozen shoulder syndrome and its treatment. The purpose
      of this paper was to review the literature and to advance clear, current
      information regarding the clinical manifestations of frozen shoulder syndrome;
      its natural history; and views regarding pathogenesis, pathophysiology, and
      treatment. Further research is necessary to elucidate a clear, factual basis for
      therapeutic interventions.

PMID- 8298630
TI  - The influence of muscle contraction on the degree of microvascular perfusion in
      rat skeletal muscle following transcutaneous neuromuscular electrical
      stimulation.
AB  - Electrotherapy is used clinically according to a variety of protocols and at
      various intensities with the intent of effecting any number of physiological
      changes. The purpose of this study was to determine if the increased degree of
      microvascular perfusion observed following 2,500 Hz transcutaneous neuromuscular
      electrical stimulation (TNMES) is dependent on evoked muscle contractions. The
      tibialis anterior (TA) and extensor digitorum longus (EDL) muscles from 30 male
      rats were analyzed. Six animals were untreated and served as controls, while the
      TA and EDL muscles of six animals were treated with TNMES at current intensities
      three times that needed to evoke a minimum visible contraction in the TA (M
      TNMES). The remaining animals were treated with gallamine, which effectively
      blocked neurally mediated muscle contraction. The TA and EDL muscles of six
      gallamine-treated rats received no TNMES and served as shams (G-Sham), six
      received M-TNMES (GM-TNMES), and six received TNMES at intensities sufficient to
      produce sustained muscle contraction with a neuromuscular blockade in place (G
      HIS). Perfused microvessels were labeled with fluorescein isothiocyanate-bovine
      serum albumin. The degree of microvascular perfusion was determined by
      calculating perfused microvessel/muscle fiber ratios (PV/F). The mean PV/F ratios
      of all groups were compared using Fisher's LSD (alpha = 0.05). When compared to
      controls, the PV/F ratios of the TA and EDL muscles in M-TNMES and G-HIS groups
      showed a significant (p < or = 0.05) increase while the G-Sham and GM-TNMES
      groups were similar to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298631
TI  - Electromyographic response of peroneal muscles in surgical and nonsurgical
      injured ankles during sudden inversion.
AB  - Because the peroneal muscles are thought to act as a safeguard against lateral
      ankle injury, it is important to study their function. This study was undertaken
      to electromyographically assess the latency between sudden unexpected ankle
      inversion and the start of peroneal muscle activity. Three groups participated in
      the study, including subjects with lateral ankle sprain rehabilitated
      nonsurgically (N = 7), sprains rehabilitated following surgery (N = 6), and
      injury-free ankles (N = 11). Peroneal latency was assessed by dropping the
      subjects into inversion from a special platform. The platform was designed so
      that either ankle could be inverted to 35 degrees without warning. The ANOVA
      revealed no significant latency differences (p > .05) between the three groups.
      The study suggests that bilateral peroneal latency is unaffected by injury.
      Although it has been thought that healthy muscles provide a defense against ankle
      sprain, their latency is not permanently affected by ankle injury or by surgery
      performed to correct defects from injury. It appears that mechanoreceptor
      impairment may be rehabilitated and that it is not a factor in ankle injury.

PMID- 8298632
TI  - The effect of test protocol instructions on the measurement of muscle function in
      adult women.
AB  - Consideration of the anatomy of the nervous system and events (ie., age, physical
      training, motor learning) that invoke changes in neural regulatory mechanisms and
      other bodily systems renders the impact of the type of instruction used to elicit
      a maximal effort in the assessment of muscle function across age, among different
      muscle groups, and for different parameters of muscle function tenuous. Hence,
      the efficacy and effect of using two types of instructions (rate vs. strength) on
      the assessment of the isometric functional capacity of six muscle groups were
      examined in women (N = 143) aged 25-74 years. The subjects were categorized by
      age into 10, 5-year groups. Measures of maximal force (MF), maximal rate of force
      increase (MR), total impulse (TI), time to MF (MFT), time to MR (MRT), and
      plateau time (PLT, time between 90% MF and MF) were obtained from the force-time
      recordings of maximal voluntary isometric contractions of the finger flexors,
      thumb extensors, elbow flexors and extensors, and ankle dorsiflexors and plantar
      flexors. Repeated measures analyses of variance indicated that instruction type
      influenced (p < .05) the magnitude and pattern of the force-time recordings, with
      the degree of difference dependent upon the muscle group and parameter of muscle
      function examined. Use of the rate instruction yielded greater MRs (40.9-541.0
      N/sec) than the strength instruction. The strength instruction elicited greater
      MFs (6.4-326.7 N), longer MFTs (0.72-1.50 sec), MRTs (0.05-0.15 sec) and PLTs
      (0.31-0.79 sec), and greater TIs (25.1-1,079.8 N-sec) than the rate
      instruction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298633
TI  - Reliability of measurements obtained by use of an instrument designed to
      indirectly measure iliotibial band length.
AB  - Ober's test is widely used to indirectly assess iliotibial band length on
      patients with painful conditions of the lower extremity. The validity of Ober's
      test is questioned on several accounts: there is no method for standardizing the
      position of the pelvis during the measurement; the scale used to describe the
      results is nominal and appears to have been arbitrarily determined; and, finally,
      the reliability of judgments made using Ober's test has not been reported. The
      purposes of this study were to develop a method for quantifying an indirect
      measurement of iliotibial band length and to examine the intratester and
      intertester reliability of measurements obtained. Iliotibial band lengths of 10
      patients (N = 10) with anterior knee pain were measured twice by each of two
      examiners. Data were analyzed using the intraclass correlation coefficient (ICC)
      and standard error of the measurement (SEM). The ICC values were 0.94 and 0.73
      for intratester and intertester reliability, respectively. The SEM values were 1
      degree and 2 degrees for intratester and intertester reliability, respectively.
      Measurements obtained with the modified method are reliable when taken on young
      patients with anterior knee pain.

PMID- 8298634
TI  - Cloning the Wilson disease gene.

PMID- 8298635
TI  - Glycine receptors: a startling connection.

PMID- 8298636
TI  - Left, right and without a cue.

PMID- 8298637
TI  - Mild ALS in Japan associated with novel SOD mutation.

PMID- 8298638
TI  - A potent genetic risk factor for restenosis.

PMID- 8298639
TI  - The Wilson disease gene is a putative copper transporting P-type ATPase similar
      to the Menkes gene.
AB  - Wilson disease (WD) is an autosomal recessive disorder of copper transport,
      resulting in copper accumulation and toxicity to the liver and brain. The gene
      (WD) has been mapped to chromosome 13 q14.3. On yeast artificial chromosomes from
      this region we have identified a sequence, similar to that coding for the
      proposed copper binding regions of the putative ATPase gene (MNK) defective in
      Menkes disease. We show that this sequence forms part of a P-type ATPase gene
      (referred to here as Wc1) that is very similar to MNK, with six putative metal
      binding regions similar to those found in prokaryotic heavy metal transporters.
      The gene, expressed in liver and kidney, lies within a 300 kb region likely to
      include the WD locus. Two WD patients were found to be homozygous for a seven
      base deletion within the coding region of Wc1. Wc1 is proposed as the gene for
      WD.

PMID- 8298640
TI  - Mapping, cloning and genetic characterization of the region containing the Wilson
      disease gene.
AB  - Wilson disease (WD) is an autosomal recessive disorder of copper transport which
      map to chromosome 13q14.3. In pursuit of the WD gene, we developed yeast
      artificial chromosome and cosmid contigs, and microsatellite markers which span
      the WD gene region. Linkage disequilibrium and haplotype analysis of 115 WD
      families confined the disease locus to a single marker interval. A candidate cDNA
      clone was mapped to this interval which, as shown in the accompanying paper, is
      very likely the WD gene. Our haplotype and mutation analyses predict that
      approximately half of all WD mutations will be rare in the American and Russian
      populations.

PMID- 8298641
TI  - The Wilson disease gene is a copper transporting ATPase with homology to the
      Menkes disease gene.
AB  - Wilson disease (WD) is an autosomal recessive disorder characterized by the toxic
      accumulation of copper in a number of organs, particularly the liver and brain.
      As shown in the accompanying paper, linkage disequilibrium & haplotype analysis
      confirmed the disease locus to a single marker interval at 13q14.3. Here we
      describe a partial cDNA clone (pWD) which maps to this region and shows a
      particular 76% amino acid homology to the Menkes disease gene, Mc1. The predicted
      functional properties of the pWD gene together with its strong homology to Mc1,
      genetic mapping data and identification of four independent disease-specific
      mutations, provide convincing evidence that pWD is the Wilson disease gene.

PMID- 8298642
TI  - Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the
      dominant neurologic disorder, hyperekplexia.
AB  - Hereditary hyperekplexia, or familial startle disease (STHE), is an autosomal
      dominant neurologic disorder characterized by marked muscle rigidity of central
      nervous system origin and an exaggerated startle response to unexpected acoustic
      or tactile stimuli. Linkage analyses in several large families provided evidence
      for locus homogeneity and showed the disease gene was linked to DNA markers on
      the long arm of chromosome 5. Here we describe the identification of point
      mutations in the gene encoding the alpha 1 subunit of the glycine receptor
      (GLRA1) in STHE patients from four different families. All mutations occur in the
      same base pair of exon 6 and result in the substitution of an uncharged amino
      acid (leucine or glutamine) for Arg271 in the mature protein.

PMID- 8298643
TI  - Chromosome 4 localization of a second gene for autosomal dominant polycystic
      kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a genetically
      heterogeneous disorder. A gene defect located on the short arm of chromosome 16
      is responsible for the disease in roughly 86% of affected European families.
      Using highly polymorphic microsatellite DNA markers, we have assigned a second
      gene for ADPKD to chromosome 4. In eight families with clear evidence against
      linkage to chromosome 16 markers, linkage analysis with the markers D4S231 and
      D4S423, demonstrated a multipoint lod score of 22.42.

PMID- 8298644
TI  - Inactivation of WT1 in nephrogenic rests, genetic precursors to Wilms' tumour.
AB  - Nephrogenic rests consist of foci of primitive renal cells, typically
      microscopic, that are found within the normal kidney tissue of children with
      Wilms' tumour. To study the relationship between nephrogenic rests and the
      associated tumours, we screened these lesions for mutations in the 11p13 Wilms'
      tumour suppressor gene, WT1. In two cases in which the Wilms' tumour contained a
      somatic WT1 mutation, the nephrogenic rest had the identical mutation.
      Nephrogenic rests and Wilms' tumours are therefore topographically distinct
      lesions that are clonally derived from an early renal stem cell. Inactivation of
      WT1 appears to be an early genetic event which can lead to the formation of
      nephrogenic rests, enhancing the probability that additional genetic hits will
      lead to Wilms' tumour.

PMID- 8298645
TI  - Localization of DNA sequences required for human centromere function through an
      analysis of rearranged Y chromosomes.
AB  - We have localized the DNA sequences required for mitotic centromere function on
      the human Y chromosome. Analysis of 33 rearranged Y chromosomes allowed the
      centromere to be placed in interval 8 of a 24-interval deletion map. Although
      this interval is polymorphic in size, it can be as small as approximately 500kb.
      It contains alphoid satellite DNA and approximately 300kb of adjacent Yp
      sequences. Chromosomes with rearrangements in this region were analysed in
      detail. Two translocation chromosomes and one monocentric isochromosome had
      breakpoints within the alphoid array. Of 12 suppressed Y centromeres on
      translocation chromosomes and dicentric isochromosomes that were also analysed
      two showed deletions one of which only removed alphoid DNA. These results
      indicate that alphoid DNA is a functional part of the Y chromosome centromere.

PMID- 8298646
TI  - Molecular modelling of the Norrie disease protein predicts a cystine knot growth
      factor tertiary structure.
AB  - The X-lined gene for Norrie disease, which is characterized by blindness,
      deafness and mental retardation has been cloned recently. This gene has been
      thought to code for a putative extracellular factor; its predicted amino acid
      sequence is homologous to the C-terminal domain of diverse extracellular
      proteins. Sequence pattern searches and three-dimensional modelling now suggest
      that the Norrie disease protein (NDP) has a tertiary structure similar to that of
      transforming growth factor beta (TGF beta). Our model identifies NDP as a member
      of an emerging family of growth factors containing a cystine knot motif, with
      direct implications for the physiological role of NDP. The model also sheds light
      on sequence related domains such as the C-terminal domain of mucins and of von
      Willebrand factor.

PMID- 8298647
TI  - Phosphorylase kinase deficiency in I-strain mice is associated with a frameshift
      mutation in the alpha subunit muscle isoform.
AB  - Heritable phosphorylase kinase (Phk) deficiency underlies a group of glycogenoses
      in humans, mice and rats that differ in mode of inheritance and tissue
      specificity. It is assumed that this heterogeneity is caused by mutations
      affecting different subunits and isoforms of Phk. As the first Phk deficiency
      mutation to be identified, we report a single-nucleotide insertion in the coding
      sequence of the Phk alpha subunit muscle isoform of the I-strain mouse. This
      mutation accounts for the virtually complete enzymatic deficiency, the tissue
      specificity and the X-linked mode of inheritance in this mutant.

PMID- 8298648
TI  - Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q.
AB  - Dopa-responsive dystonia (DRD) is an autosomal-dominant neurological disorder
      which appears to result from a genetically determined deficiency of striatal
      dopamine. Pathological evidence suggests that this may be due to the
      establishment of a reduced number of dopaminergic nerve terminals in the
      striatum, or to an excessive reduction (pruning) of these terminals in early
      development. We have mapped the DRD gene to chromosome 14 by linkage analysis in
      3 families with a maximum 2-point lod score of 4.67 at 8.6 centiMorgans from
      D14S63; maximum multipoint lod scores > 6 were obtained for the intervals D14S47
      D14S52 and D14S52-D14S63. The flanking loci D14S47 and D14S63 define a region of
      about 22 cM as containing the DRD gene.

PMID- 8298649
TI  - Linkage of Bardet-Biedl syndrome to chromosome 16q and evidence for non-allelic
      genetic heterogeneity.
AB  - Bardet-Biedl syndrome is an autosomal recessive disorder characterized by mental
      retardation, obesity, retinitis pigmentosa, polydactyly and hypogonadism. Other
      findings include hypertension, diabetes mellitus and renal and cardiovascular
      anomalies. We have performed a genome-wide search for linkage in a large inbred
      Bedouin family. Pairwise analysis established linkage with the locus D16S408 with
      no recombination and a lod score of 4.2. A multilocus lod score of 5.3 was
      observed. By demonstrating homozygosity, in all affected individuals, for the
      same allele of marker D16S408, further support for linkage is found, and the
      utility of homozygosity mapping using inbred families is demonstrated. In a
      second family, linkage was excluded at this locus, suggesting non-allelic genetic
      heterogeneity in this disorder.

PMID- 8298650
TI  - Adenovirus mediated expression of therapeutic plasma levels of human factor IX in
      mice.
AB  - Gene therapy strategies designed to combat haemophilia B, caused by defects in
      clotting factor IX, have so far concentrated on ex vivo approaches. We have now
      evaluated adenoviral vector-mediated expression of human factor IX in vivo.
      Injection of the vector Av1H9B, which encodes human factor IX cDNA, into the tail
      veins of mice resulted in efficient liver transduction and plasma levels of human
      factor IX that would be therapeutic for haemophilia B patients. However, levels
      slowly declined to baseline by nine weeks and were not re-established by a second
      vector injection. These results address both the advantages and obstacles to the
      use of adenoviral vectors for treatment of haemophilia B.

PMID- 8298651
TI  - Mapping a gene for familial situs abnormalities to human chromosome Xq24-q27.1.
AB  - Ambiguous abdominal situs, asplenia/polysplenia and severe cardiac malformations
      characterize heterotaxy in humans. These anomalies result from the inability of
      the developing embryo to establish normal left-right asymmetry. We have studied
      an interesting family in which the heterotaxy phenotype segregates as an X-linked
      recessive trait. In order to map the heterotaxy locus (HTX), we have analysed 39
      family members using highly-polymorphic microsatellite markers from the X
      chromosome. One of these markers, DXS994, shows no recombination with the disease
      locus in 20 informative meioses. Linkage analysis results in a maximum lod score
      of 6.37. Current genetic and physical mapping data assign the order of loci in
      Xq24-q27.1 as cen-DXS1001-(DXS994, HTX)-DXS984-tel. These results establish the
      first mapping assignment of situs abnormalities in humans.

PMID- 8298652
TI  - Constitutional relaxation of insulin-like growth factor II gene imprinting
      associated with Wilms' tumour and gigantism.
AB  - We have examined the imprinting of the insulin-like growth factor II gene (IGF2)
      in ten normal kidney samples from children with renal embryonal neoplasms. In
      kidney samples from nine children with normal growth profiles, IGF2 mRNA was
      transcribed monoallelically, consistent with normal imprinting of the gene. But
      in one child who had generalized somatic overgrowth, IGF2 was transcribed from
      both alleles in her kidney, peripheral blood leukocytes and Wilms' tumour. These
      findings suggest that a defect in genomic imprinting can occur constitutionally,
      leading to growth abnormalities and predisposition to Wilms' tumour.

PMID- 8298653
TI  - Characterization of molecular defects in xeroderma pigmentosum group C.
AB  - Xeroderma pigmentosum (XP) is a rare autosomal recessive disease of humans
      characterized by an accelerated chronic degeneration of sun-exposed areas of the
      body, including an elevated risk of developing cancers of the skin. We recently
      reported the isolation of a gene XPCC that complements the repair deficiency of
      cultured XP-C cells. Here we report the results of a characterization of XPCC at
      the nucleotide level in five XP-C cell lines. Each cell line exhibited a unique
      mutation that correlated well with the cellular DNA repair deficiency and the
      clinical severity of the disease. These results extend our previous observations
      and indicate that defects in XPCC cause Xeroderma pigmentosum group C.

PMID- 8298654
TI  - Neosporosis associated congenital limb deformities in a calf.

PMID- 8298655
TI  - A Trichomonas vaginalis cDNA with partial protein sequence homology with a
      Plasmodium falciparum excreted protein ABRA.
AB  - We have previously isolated two extracellular cysteine proteases (60 kDa, 30 kDa)
      from the cell filtrate of an isolate of Trichomonas vaginalis. All isolates
      tested produced a 60 kDa protease as demonstrated by immunoblot with cross
      reacting rabbit serum. A T. vaginalis cDNA library was constructed using lambda
      gt11. A 760 bp T. vaginalis specific cDNA was sequenced and demonstrates partial
      protein sequence homology with an extracellular cysteine protease of Plasmodium
      falciparum. These results are consistent with the hypothesis that this protease
      may be important in the pathogenesis of T. vaginalis infection.

PMID- 8298656
TI  - Observations on the epidemiology of human taeniasis amongst the Goemai tribe of
      northern Nigeria.
AB  - A study on the epidemiology of human taeniasis amongst the Goemai tribe of Kwande
      rural community of Qua'an Pan Local Government Area carried out between January
      and June, 1991 is reported. 115 or 11.5% of the 1,000 persons examined were
      infected. Of the 614 males and 386 females examined, 77 (12.5%) and 38 (9.9%)
      respectively had infections. No significant difference in prevalence rates was
      recorded between the sexes and age groups. Infection was significantly higher (P
      < 0.05) among farmers than other occupational categories, and in those eating
      half roasted/cooked meat than in persons eating well-cooked meat. Other
      epidemiological factors relating to type of toilet facilities used as well as
      some socio-cultural and traditional beliefs of Goemai people which encourage host
      parasite contact and their implications for public health are discussed.
      Suggestions are made for the control of human taeniasis in the community.

PMID- 8298657
TI  - Visceral leishmaniasis: II. Histiocyte ultrastructure in bone marrow associated
      with low level of parasitaemia and mimicking malignant histiocytosis.
AB  - The ultrastructural features of histiocytes in the bone marrow (BM) were studied
      in a febrile, splenomegalic and pancytopenic Sudanese patient who was diagnosed
      by one of us as visceral leishmaniasis (VL) associated with low level of
      parasitaemia and mimicking malignant histiocytosis (MH). Serial thick (STS) and
      ultrathin (SUT) sections showed that the BM was hypercellular and markedly
      infiltrated by large histiocytes with prominent phagocytosis. A thorough
      examination of various ST and UT section revealed only a single, typical Leishman
      Donovan body. At transmission electron microscopy (TEM) level, two principal
      types of histiocytic cells were identified: Type I, subdivided into two subtypes,
      were actively phagocytic histiocytes (PH) with large digestive vacuoles and
      primary lysosomes; type II were nonphagocytic histiocytes (nPH) with primary
      lysosomes only. The rate of PH to nPH ws 7:2 in plastic STS. The interaction
      between the PH and ingested cells is described. Both types of cell were
      morphologically similar to previously described malignant histiocytic cells.
      However, this study showed a better characterization of PH during VL.

PMID- 8298658
TI  - Human bilharzial ureters: III. Fine structure of the egg granuloma.
AB  - The fine structure of egg granuloma forming cells is described in lower ureteral
      segments of patients chronically infected with Schistosoma haematobium. The
      infiltrates consisted of monocytes, macrophages, lymphocytes, plasma cells,
      neutrophils, eosinophils, fibroblasts, mast cells, and blood platelets. The
      abundant monocytes and macrophages were actively mobile and intensively
      phagocytic cells. Multinucleate giant macrophages were only seen within empty egg
      shells. In addition to normal looking lymphocytes and plasma cells, several
      lymphocyte-like Sezary cells characterized by strikingly convoluted "cerebriform"
      nuclei were observed. Mature neutrophils and eosinophils were detected in
      addition to abnormal looking neutrophils; these contained numerous filamentous
      bundles. Fibroblasts were associated with extracellular collagen fibers and an
      electron-dense material. The few mast cells seen in proximity to blood vessels
      have a feature consistent with the onset of degranulation. Few blood platelets
      with active phagocytic features were among the granuloma cells.

PMID- 8298659
TI  - Prevalence of Pthirus pubis (Anoplura: Pediculidae) among sex workers in urban
      Jos, Nigeria.
AB  - Between May and October 1992, 374 sex workers comprising of 372 prostitutes and 2
      homosexuals were examined for Pthirus pubis infestation. While none of the
      homosexuals was found to be infested, 52.69% of the prostitutes were infested
      with the highest and lowest infestation in the 40-49 year old group and 20-29
      year old group respectively. The educational level was found to determine the
      extent of disease awareness among the sex workers. Questions are raised about the
      role of Pthirus pubis is AIDS transmission among sex workers.

PMID- 8298660
TI  - [Morphological studies of Babesia divergens during continuous transfer in
      Meriones unguiculatus].
AB  - A strain of Babesia divergens was propagated by inoculation of 1.5 x 10(7)
      parasitized erythrocytes in 30 passages under same conditions on altogether 150
      jirds. The developmental stages of Babesia divergens revealed pleomorphism in the
      erythrocytes of the jird. Single parasites were observed as being pyriform,
      globular, budding, ring-like or amoebid. The shape of dividing parasites varied
      between the spherical and the pyriform. The stages in the erythrocytes were
      localized predominantly intermedia. The reduction of the number of dividing forms
      and the increase of single forms occurred with increasing numbers of passages.
      Length and breadth of double pyriforms increased by approximately 20%.

PMID- 8298661
TI  - The prevalence of small terrestrial mammals infected with tick-borne encephalitis
      virus and leptospirae in the foothills of the southern Bavarian forest, Germany.
AB  - In the district of Grafenau/Freyung (Bavaria, Germany), 266 specimens of small
      terrestrial mammals of 8 species were captured using live traps. From these
      mammals, Apodemus flavicollis (42.1%) and Clethrionomys glareolus (39.5%) were
      prevalent. All animals were tested for neutralizing antibodies to tick-borne
      encephalitis (TBE) virus and agglutinating antibodies to leptospirae.
      Seropositivity against TBE virus was 14.0% and against leptospirae 7.9%,
      respectively. Seropositivity to leptospirae appeared to be primarily to
      Leptospira grippotyphosa, less to Australis and occasionally to Javanica
      serovars. Only one A. flavicollis specimen was positive to both pathogens tested.
      The parasitocoenosis of trapped micromammals with ectoparasites consisted of
      69.5% from ticks (mainly Ixodes ricinus, less from I. trianguliceps), 16.1% of
      mites (primarily Laelaps agilis) and 14.3% of fleas (mostly Ctenophthalmus
      agyrtes).

PMID- 8298662
TI  - Biochemical characterisation of Trichinella spiralis and T. pseudospiralis
      stichocyte antigens.
AB  - One and two dimensional Western blots of Trichinella spiralis and Trichinella
      pseudospiralis extracts were probed with a monoclonal antibody (7C2C5) which
      recognizes molecules found in the stichocytes. Three major antigens were revealed
      in excreted:secreted (E/S) preparations at approx Mr 45, 53 & 60 X 10(3). The Mr
      45 X 10(3) molecule was the most abundant secreted antigen, on two dimensional
      analysis it resolved into many isoforms with a pI range 4.5-6.4 in T. spiralis
      and into four isoforms pI range 5.1-5.7 in T. pseudospiralis.

PMID- 8298663
TI  - Resistance of the German cockroach Blattella germanica (L.) to dioxacarb in
      Bulgaria.
AB  - The level of susceptibility of 15 wild populations Blattella germanica (L.) from
      9 various regions in Bulgaria to dioxacarb was studied. The compound was applied
      by jar impregnation. The method recommended by WHO was used. LT50s and LT90s were
      calculated. These values were compared with those observed for the laboratory
      strain. A total of 4,080 males, females and nymphs were tested. Low to high
      resistance with Ri = 1.54X ... 25.38X at LT50 was established.

PMID- 8298664
TI  - Abnormal uterine bleeding in the perimenopause.
AB  - Abnormal uterine bleeding is probably one of the most common gynecologic
      complaints in the perimenopause. It is a significant cause of hysterectomy, which
      is the second most common surgical procedure performed on women in the United
      States, and thus is a major health issue. Management consists of a stepwise
      evaluation of all possible organic causes of uterine bleeding. Advancements in
      technology have allowed considerable improvements in the resolution of many
      diagnostic tools. Direct visualization of the uterine cavity is now an invaluable
      adjunct to blind endometrial sampling. Consequently, therapy can be tailored more
      appropriately and efficiently, either by newly developed medical strategies or
      through selective, minimally invasive surgery. In light of these perspectives,
      some of the recent diagnostic and therapeutic trends in the management of
      abnormal uterine bleeding in perimenopausal women are presented.

PMID- 8298665
TI  - Ovulation induction with GnRH agonist and human menopausal gonadotropins:
      response in patients with one versus two ovaries.
AB  - OBJECTIVE: To examine the effect of oophorectomy on response to gonadotropin
      releasing hormone-agonist/human menopausal gonadotropin (GnRH-a/hMG) for in vitro
      fertilization (IVF). DESIGN: Retrospective review. SETTING: Tertiary care
      academic institution. PATIENTS: Ninety-one infertile patients undergoing IVF.
      Eighty-four women had two ovaries and seven had only one ovary. RESULTS: There
      was no difference observed between women with one versus two ovaries with regard
      to response to medications, hormone production, number of oocytes retrieved and
      fertilized, or the number of embryos cleaved and transferred. CONCLUSION: Women
      with only one ovary are at no reproductive disadvantage when undergoing ovulation
      induction for IVF.

PMID- 8298666
TI  - Cycle control with desogestrel-containing oral contraceptives--comparison of a
      monophasic and triphasic regimen.
AB  - OBJECTIVE: To examine the effect of mono- and triphasic desogestrel-containing
      oral contraceptives on cycle control. SETTING: Multicenter, international (U.S.
      and Canada). PATIENTS AND INTERVENTIONS: About 4,000 women, aged 18-35, healthy,
      neither pregnant nor lactating, were followed for almost 37,700 cycles of use of
      a monophasic 150 micrograms desogestrel/30 micrograms ethinyl estradiol OC or
      Sunday- or day-1 start regimens of a triphasic preparation containing 50/100/150
      micrograms desogestrel/35/30/30 micrograms ethinyl estradiol administered on a
      7/7/7 schedule. Standard diary methods were used to collect data on breakthrough
      bleeding, spotting, and absence of withdrawal bleeding. RESULTS: The two
      formulations demonstrated very low and, in fact, remarkably similar rates of
      breakthrough bleeding, spotting, and absence of withdrawal bleeding. A
      statistical analysis of these characteristics of the total study populations, per
      cycle, revealed no statistically significant differences between the
      formulations. CONCLUSION: Although the triphasic formulation contains the lowest
      estrogen dose of any triphasic available, 33% less progestin than the monophasic
      formulation, it maintains comparable cycle control.

PMID- 8298667
TI  - HLA class I, class II, and class III antigen sharing is not found in couples with
      unexplained infertility.
AB  - OBJECTIVE: To find the degree of HLA antigen sharing in couples with infertility
      of unknown etiology and compare it with that in couples with infertility of known
      etiology as well as couples with normal fertility. SUBJECTS: Eleven couples with
      infertility of unknown etiology, 26 with infertility of known etiology, and 31
      fertile couples were tested for HLA class I (A, B, C), class II (DR, MLC), and
      class III (Bf) antigens and GLO alleles. HLA lymphocytotoxic antibodies and anti
      sperm antibodies in both partners were also searched. RESULTS: Gene frequencies
      and the number of HLA antigens shared between the two members of the couple were
      similar in all groups. When "intra-couple" MLC reactivity was measured, no
      quantitative differences were found in the infertile group with unknown etiology,
      as compared to the group of known etiology: spouses in couples of either group
      usually reacted in both ways as expected for unrelated individuals" lymphocytes.
      Lymphocytotoxic antibody frequency did not differ between the nonfertile groups,
      and anti-sperm antibodies, found in ten patients in the group of known etiology,
      were not associated with any HLA antigen. In spite of that, GLO and all the HLA
      antigen classes described (I, II and III) were analyzed. CONCLUSIONS: Although
      the results are negative, these and others' (negative) results concerning couples
      with infertility of unknown etiology do not disprove that HLA has a role in
      fertilization, because HLA-related factors still unknown may exist. Exhaustive
      HLA available marker typing in international cooperative efforts may be needed to
      reach a significant number of carefully selected couples fully HLA typed to
      elucidate this problem.

PMID- 8298668
TI  - Growth hormone--non multum sed multa (quality, not quantity).
AB  - In view of the recent availability of recombinant human growth hormone (GH) and
      reports of its ability to augment ovulation induction by exogenous gonadotropins,
      we have surveyed the reproductive physiological role of GH and the family of
      polypeptides that mediate its action. The clinical studies using GH to improve
      ovulation induction, although achieving a significant reduction in exogenous
      gonadotropin administration, show only minor benefits in terms of attainment of
      pregnancy. An explanation for this phenomenon is suggested, and we provide
      guidelines for whom GH should be recommended.

PMID- 8298669
TI  - Positive effect of balneotherapy on post-PID symptoms.
AB  - OBJECTIVE: The aim of this study was investigation of effect of balneotherapy
      after antibiotic treatment of PID. PATIENTS AND INTERVENTIONS: Fifty-seven
      patients with PID, diagnosed by laparoscopy, were treated by the same antibiotic
      scheme (oxytetracycline and metronidazole). After treatment of the acute phase,
      we studied the effect of balneotherapy (mud baths or mud packs, mineral baths,
      electrotherapies, and gynecological exercises) under sanatorium conditions in 30
      patients. Twenty-seven patients without balneotherapy served as a control group.
      Second-look laparoscopy with dye insufflation was carried out about 12 weeks
      after the first operation. RESULTS: The rate of tubal occlusion after
      balneotherapy was 31% vs. 28% in patients without balneotherapy (P > .05).
      Moderate or severe adhesions seen at first look were similar in both groups
      (40.7% vs. 46.7%) and were nearly unchanged during second-look laparoscopy (44.4%
      vs. 46.6%). Twelve of 27 (44.4%) control patients had subjective or objective
      complaints compared to only 2 of 30 (6.7%, P < .05). CONCLUSION: Although
      balneotherapy after antibiotic therapy for acute PID does not improve fallopian
      tube patency, it is useful to reduce the frequency of lower abdominal pain.

PMID- 8298670
TI  - Colchicine inhibits spermatozoal motility in vitro.
AB  - OBJECTIVE: To study the in vitro effect of colchicine on the motility of normal
      human spermatozoa. METHODS: Seminal fluid was obtained from 15 normal healthy
      volunteers. Following the swim-up technique for sperm selection, samples of sperm
      were incubated with different concentrations of colchicine and their forward
      motility was assessed after 2, 17, and 24 hours. RESULTS: Colchicine
      concentrations of 10 micrograms/mL and 20 micrograms/mL reduced spermatozoal
      motility, while a concentration of 2 micrograms/mL did not have a significant
      inhibitory effect. Reduction in motility was observed after a minimum incubation
      of 18 hours. After 24 hours 90-95% of the spermatozoa was shown to be viable by
      eosin staining. CONCLUSION: Relatively high concentration of colchicine may
      affect in vitro motility of sperm, probably by its direct effect on the
      microtubules rather than by causing spermatozoal death.

PMID- 8298671
TI  - DNA flow cytometry of sperm from normozoospermic men in barren couples and men of
      proven fertility.
AB  - OBJECTIVE: To determine the extent to which sperm chromatin varies in its degree
      of condensation in 53 apparently normozoospermic men and in 14 men of proven
      fertility. METHODS: DNA flow cytometry after staining of spermatozoa with
      ethidium bromide and mithramycin. RESULTS: Normozoospermic men could be divided
      into four subgroups according to the fluorescence pattern of their sperm DNA.
      More than half of the normozoospermic group and all of those of proven fertility
      shared a similar profile with a narrow symmetrical peak of haploid fluorescence
      without significant sub-populations. Deviations from this pattern were generally
      not associated with any major differences in sperm quality. CONCLUSIONS: (a)
      Current criteria for normozoospermia should be expanded to include additional
      tests of biochemical integrity. (b) Fertilizing ability appears to be associated
      with a relatively homogeneous profile of sperm DNA condensation.

PMID- 8298672
TI  - Correlation between the hypoosmotic swelling test and various sperm function
      tests.
AB  - OBJECTIVE: To compare the hypoosmotic swelling test (HOST) with other sperm
      function assays. MATERIALS AND METHODS: The HOST was performed on 105 patients
      with idiopathic infertility. The results were compared with those of various
      other sperm function tests, including the sperm penetration assay (SPA), triple
      stain technique for evaluating acrosomal reactions, and the in vitro cervical
      mucus penetration test (Penetrak). RESULTS: A strong positive correlation was
      observed between percent sperm motility and the percent swollen sperm, between
      the motile sperm concentration and sperm swelling, and between sperm swelling and
      penetration values. Only a weak correlation was detected between sperm swelling
      and the percent sperm penetration. However, most of the cases with a sperm
      swelling percentage of 50% or more had good sperm penetration into ova.
      CONCLUSIONS: The HOST was useful to evaluate sperm tail function and was found
      valuable as a screening test prior to the SPA.

PMID- 8298673
TI  - Levels of insulin and cholesterol in human follicular fluid.
AB  - OBJECTIVE: The intent of this study was to ascertain if there was a correlation
      between insulin and cholesterol levels in follicular fluid and oocyte
      fertilizability and developmental potential. MATERIALS AND METHODS: The levels of
      immunoreactive cholesterol, total cholesterol, high-density lipoprotein
      cholesterol, very-low-density lipoprotein-cholesterol were determined in
      follicular lipoprotein-cholesterol were determined in follicular fluid samples
      obtained during transabdominal-transvesicular aspiration of follicles under
      ultrasound guidance, from patients treated with clomiphene citrate and human
      menopausal gonadotropin for in vitro fertilization. Insulin was measured by
      radioimmunoassay and cholesterol by an enzymatic method. RESULTS: Follicles
      containing oocytes with better fertilizability and greater developmental
      potential possessed lower concentrations of immunoreactive insulin and high
      density lipoprotein-cholesterol, and higher concentrations of low-density
      lipoprotein- and very-low-density lipoprotein-cholesterol. CONCLUSION: These
      lipoprotein- and very-low-density lipoprotein-cholesterol. CONCLUSION: These
      changes in the level of cholesterol carried by the various lipoproteins in the
      follicular fluid strongly suggest that oocyte maturation is influenced by insulin
      dependent steroidogenesis.

PMID- 8298674
TI  - The joy of reading.

PMID- 8298675
TI  - Working with pictures.

PMID- 8298676
TI  - A nurse's guide to being on a review.

PMID- 8298677
TI  - Get smart at work.

PMID- 8298678
TI  - Top job closed to nurses aides.

PMID- 8298679
TI  - Off the ladder. Interview by Teresa O'Connor.

PMID- 8298680
TI  - Room at the top.

PMID- 8298681
TI  - Looking back.

PMID- 8298682
TI  - Auditing standards for practice: 10 ways to make it happen.

PMID- 8298683
TI  - Crystallization of membrane proteins for X-ray analysis.

PMID- 8298684
TI  - Measurement of lipid-protein interactions in reconstituted membrane vesicles
      using fluorescence spectroscopy.

PMID- 8298685
TI  - Determination of the transverse topography of membrane lipids using enzymes and
      covalent labels as probes.

PMID- 8298686
TI  - Determination of the transverse topography of membrane phospholipids using
      phospholipid transfer proteins as tools.

PMID- 8298687
TI  - Prothrombinase complex as a tool to assess changes in membrane phospholipid
      asymmetry.

PMID- 8298688
TI  - Fluorescent glycerolipid probes. Synthesis and use for examining intracellular
      lipid trafficking.

PMID- 8298689
TI  - Synthesis and use of spin-labeled lipids for studies of the transmembrane
      movement of phospholipids.

PMID- 8298690
TI  - Measurement of membrane fluidity and membrane fusion with fluorescent probes.

PMID- 8298691
TI  - Extraction and assay of cyclic nucleotides.

PMID- 8298692
TI  - Determination of cell-surface polarity by solid-phase lactoperoxidase iodination.

PMID- 8298693
TI  - Analysis of G-proteins regulating signal transduction pathways.

PMID- 8298694
TI  - Assay of protein kinases and protein phosphorylation.

PMID- 8298695
TI  - Analysis of cellular phosphoinositides and phosphoinositols by extraction and
      simple analytical procedures.

PMID- 8298696
TI  - Analysis of cellular phosphoinositides and phosphoinositols by high-performance
      liquid chromatography.

PMID- 8298697
TI  - Cytosolic free calcium measurements in single cells using calcium-sensitive
      fluorochromes.

PMID- 8298698
TI  - Membrane permeabilization with bacterial toxins.

PMID- 8298699
TI  - Measurement of ion fluxes and pH gradients across cell membranes.

PMID- 8298700
TI  - Biochemical methods to determine cell-surface topography.

PMID- 8298701
TI  - Ligand binding and processing. The perfused liver as a model system.

PMID- 8298702
TI  - The binding of protein-ligands to cell-surface receptors.

PMID- 8298703
TI  - Use of antipeptide antibodies for the isolation and study of membrane proteins.

PMID- 8298704
TI  - The production of monoclonal antibodies to membrane proteins.

PMID- 8298705
TI  - Purification of a membrane protein (Ca2+/Mg(2+)-ATPase) and its reconstitution
      into lipid vesicles.

PMID- 8298706
TI  - Measurement of protein-protein interactions in reconstituted membrane vesicles
      using fluorescence spectroscopy.

PMID- 8298707
TI  - Biochemical properties of aeroallergens: contributory factors in allergic
      sensitization?
AB  - Recent studies indicate that the majority of clinically important aeroallergens
      are biochemically active. A diverse range of properties have been demonstrated
      but most possess either enzymatic activity (principally hydrolytic), enzyme
      inhibitory activity, low molecular weight ligand transporting or regulatory
      properties. In addition, some allergens are glycosylated and/or are structurally
      similar to proteins which have evolved to function in the respiratory system per
      se. Little attention has been given to the possibility that the biochemical
      activity of an allergen or any post-translational modifications contribute to
      sensitization. In this review, mechanisms with the potential to influence
      immunogenicity are discussed including interaction with respiratory secretions,
      epithelial disruption, interactions with immunocompetent cells and receptor
      mediated endocytosis. Given that many aeroallergens are structurally and
      functionally similar to a variety of endogenous (e.g. lysosomal enzymes) and
      exogenous proteins (e.g. microbial enzymes and glycoproteins), particular
      attention has been directed to the latter. This process represents an important
      non-adaptive defence mechanism which has evolved to recognize and process such
      proteins and it is feasible that it plays a similar role in the processing of
      some allergens entering the respiratory system.

PMID- 8298708
TI  - Preventive effect of feeding high-risk infants a casein hydrolysate formula or an
      ultrafiltrated whey hydrolysate formula. A prospective, randomized, comparative
      clinical study.
AB  - In a prospective study of a 1-year birth cohort of 158 high-risk infants the
      effect of feeding breastmilk, a casein hydrolysate (Nutramigen) or a new
      ultrafiltrated whey hydrolysate (Profylac) on the development of cow milk protein
      allergy/intolerance (CMPA/CMPI) was assessed and compared. All the infants had
      biparental or severe single atopic predisposition, the latter combined with cord
      blood IgE > or = 0.5 kU/L. At birth all infants were randomized to Nutramigen or
      Profylac, which was used when breastfeeding was insufficient or not possible
      during the first 6 months of life. During the same period this regimen was
      combined with avoidance of solid foods and cow milk protein. All mothers had
      unrestricted diets and were encouraged to do breastfeeding only. Moreover,
      avoidance of daily exposure to tobacco smoking, furred pets and dust-collecting
      materials in the bedroom was advised. The infants were followed prospectively
      from birth to 18 months of age. All possible atopic symptoms were registered and
      controlled elimination/challenge studies were performed when symptoms suggested
      CMPA/CMPI. A total of 154 (97%) were followed up and 141 followed the diet
      strictly. Eighty-eight (62%) of the infants were breastfed for at least 6 months,
      20 (14%) were breastfed exclusively, 59 and 62 had varying amounts of Nutramigen
      or Profylac respectively. CMPA/CMPI was diagnosed in 1/20, 1/59 and 3/62 in the
      breastfed, the Nutramigen and Profylac groups respectively, but 1 of the latter
      also had Nutramigen. None of the infants showed reactions against Nutramigen or
      Profylac. In 4 infants symptoms were provoked by breastmilk when the mother
      ingested cow milk and in 1 only by cow milk.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298709
TI  - Appearance of IgE antibodies to ingested and inhaled allergens during the first
      12 years of life in atopic and non-atopic children.
AB  - The appearance and course of serum immunoglobulin E-antibodies (IgE-ab) to egg
      white (EW), cow's milk (CM) and inhalants (pollen, danders and mite) were
      followed from birth to 12 years of age in 84 children unselected for family
      history of atopy. During the follow-up 36 children developed atopic symptoms and
      48 children did not. IgE-ab to EW and CM reached a peak prevalence at 8 months of
      age--with high concentrations almost exclusively in atopics and disappeared
      successively during childhood. IgE-ab to inhalants appeared from 2 years of age
      and then in increasing frequency during childhood. Similar to the pattern of IgE
      ab to EW and CM, transient low levels of IgE-ab to inhalants were commonly
      encountered in non-atopic children while high concentrations without tendency to
      decline were almost exclusively seen in atopics. High responders to EW-antigen
      during infancy were usually also high responders to inhalants during childhood.
      Clinical allergy to EW and CM and subsequent tolerance appeared early in
      childhood, whereas allergy to inhalants appeared later and did not disappear. The
      temporary low-grade IgE antibody response in non-atopic individuals to eaten and
      inhaled allergens is similar to the results of animal studies demonstrating a
      transient IgE production followed by tolerance.

PMID- 8298710
TI  - Interfering factors to sensitivity and specificity of bronchial reactivity in
      children.
AB  - Bronchial reactivity to carbachol, estimated by the PD65, the provocation dose of
      inhaled carbachol inducing a 65% increase of baseline respiratory resistance, was
      measured in 355 asthmatic children (age 8.7 +/- 2.6 years) and 149 healthy
      children (age 11.8 +/- 2.3 years). The frequency distribution of PD65 showed
      apart from 2 minima at 480 micrograms and 960 micrograms 2 significant peaks at
      240 micrograms (p = 0.003) and 1200 micrograms (p = 0.01) to carbachol,
      reflecting a hyperreactive class (PD65 < 480 micrograms), an intermediate class
      (481 micrograms < PD65 < 960 micrograms) and a normo-reactive class (PD65 > 961
      micrograms). The intermediate class is characterised by a considerable overlap
      between "health" and "disease". However, taking into account the degree of air
      pollution in which healthy children are living (best related factor to
      specificity) and the type of initial lung function disorder in asthmatic
      children, (the MEF50 to be the best related factor for specificity), weighed
      specificity and sensitivity improved from 64 to 88%. Evaluating bronchial
      responsiveness in children, such interfering factors should be strongly
      considered.

PMID- 8298711
TI  - Immunologic disturbances in cow's milk allergy, 1: Delayed maturation of
      suppressor activity.
AB  - To assist in identifying pathogenetic mechanisms in different subtypes of cow's
      milk allergy (CMA), the function of immunoregulatory T-lymphocytes was studied.
      The study population consisted of 23 patients, mean [95% confidence interval] age
      of 25.6 [19.5, 33.6] months, who had challenge-proven cow's milk allergy
      manifested with either skin (n = 9) or gastrointestinal (n = 14) symptoms; in
      addition, 13 age-matched disease controls were studied. Patients with challenge
      proven CMA were rechallenged to establish whether they had acquired clinical
      tolerance to cow's milk. The suppressor activity of isolated lymphocytes was
      measured in vitro by a cell coculture at rechallenge and in 10/23 patients at
      diagnosis. At diagnosis, patients with CMA (n = 10) showed a decreased mean [95%
      CI] suppressor activity, induced by either Concanavalin A, 7[-2,15]%, or cow's
      milk, 3[-8,14]% as compared with disease controls (n = 13), 19[15,24]% and
      24[17,31]%; F = 7.1, p = 0.004 and F = 6.7, p = 0.005, respectively. At
      rechallenge the suppressor activity, induced both by Concanavalin A and cow's
      milk, reached the level of disease controls only in patients who had acquired
      clinical tolerance to cow's milk (n = 13/23), but not in those retaining CMA (n =
      10/23). Our results indicate that the maturation of suppressor function is
      delayed in CMA, which might be of primary importance in the etiopathogenesis of
      CMA.

PMID- 8298712
TI  - Immunologic disturbances in cow's milk allergy, 2: Evidence for defective
      interferon-gamma generation.
AB  - We have investigated the role of interferon-gamma (IFN-gamma) in the regulation
      of antigen-specific T-cell function in patients with cow's milk allergy. The
      study population consisted of 22 patients, aged from 7.6 to 56.9 months, who had
      challenge-proven cow's milk allergy (CMA) manifested with either skin (n = 9) or
      gastrointestinal (n = 13) symptoms. In addition, 11 age-matched children and 6
      adults, mean (SD) age 31 (7) years, were studied as controls. Patients with
      challenge-proven CMA were rechallenged to establish whether they had acquired
      clinical tolerance to cow's milk. The spontaneous and mitogen-induced IFN-gamma
      and interleukin-4 (IL-4) generation of isolated lymphocytes was evaluated in
      vitro with commercial ELISA Kits at diagnosis and at reassessment. At diagnosis,
      the IFN-gamma production was not detectable in patients with CMA as compared with
      control children. IL-4 production was almost undetectable in all subjects in this
      study. However, at reassessment the CMA patients who had acquired clinical
      tolerance to cow's milk (n = 16) showed enhanced IFN-gamma production, when
      compared with that of control children, but still lower when compared with that
      of healthy adults. Our results indicate that the maturation of IFN-gamma
      producing T-cells is delayed in CMA, which could lead to a disturbance in the
      regulation of T-cell function. This defect might be an important etiologic factor
      for CMA.

PMID- 8298713
TI  - Chronic meningococcemia in a child with a deficiency of the sixth component of
      complement.
AB  - Chronic meningococcemia represents an uncommon manifestation of meningococcal
      disease. Microbial and host factors which may predispose to this form of
      meningococcal disease are not understood. Although acute meningococcal disease is
      frequently found in patients with terminal complement deficiencies, the
      relationship of chronic meningococcemia to complement deficiencies is unclear. We
      present a case report and a review of the literature describing chronic
      meningococcemia in association with deficiencies of the complement system. A
      total of eight cases were identified, all of whom were male. Six of the eight
      patients were children and two of the eight had a previous history of
      meningococcal disease. This case report, in conjunction with the previously
      reported cases, suggests an association between complement deficiencies and
      chronic meningococcemia.

PMID- 8298714
TI  - Serial IgG and IgM serum levels after infusion of different Ig-preparations (IgG
      or IgM-enriched) in preterm infants.
AB  - Intravenous administration of Immunoglobulin (IVIG) has been used for prevention
      or treatment of neonatal sepsis. However, therapeutic efficacy of IVIG is
      dependent on pharmacokinetic factors. There have been no comparative studies in
      neonates between licensed IgG and IgM enriched preparations. The aim of this
      study was to investigate serial IgG and IgM serum levels during the neonatal
      period in two groups of non-septic, preterm infants treated prophylactically with
      IVIG. Twenty-two very low birth weight (VLBW) patients (1001-1500g) (gestational
      age 31.8 +/- 2.0 weeks and 1265 +/- 245g birth weight) and 12 extremely low birth
      weight (ELBW) patients (< 1000g) (gestational age 28.6 +/- 2.5 weeks and 910-85g
      birth weight) received at random three standard doses of Sandoglobulin (SG) (0.5
      g/kg/day) or IgM enriched Pentaglobin (PG) (5 ml/kg/day). IgG and IgM
      concentrations were assayed by rate nephelometry before treatment and at day 3,
      5, 7, 14 and 28 of life. At any time IgG levels were higher in the SG-VLBW group
      (p < 0.01), no difference being observed in the ELBW group (p > 0.5). IgM levels
      were higher at day 3 and 5 in the PG-VLBW group and until day 7 in the ELBW group
      (p < 0.01). This study indicates a wide range of IgG and IgM kinetics in the
      healthy premature and suggests frequent monitoring of immunoglobulin serum levels
      during efficacy studies.

PMID- 8298715
TI  - Roles of eosinophils and catecholamines in pathophysiology of exercise-induced
      asthma.
AB  - To study the roles of eosinophils and catecholamines in the pathophysiology of
      exercise-induced asthma (EIA), an exercise challenge test was performed in 22
      asthmatic children, using a bicycle ergometer, and the changes in lung function,
      plasma norepinephrine (NE), epinephrine (E) and eosinophil cationic protein (ECP)
      levels with exercise were evaluated. Subjects were classified into three groups
      from the results of lung function test, respectively: EIA-negative group. EIA
      positive groups with good recovery and poor recovery. Eosinophil counts before
      exercise in the EIA-positive groups were significantly higher than those in the
      EIA-negative group. The ECP levels rose with exercise in all groups. Five minutes
      after exercise, ECP values fell to the pre-exercise level in the EIA-negative
      group, but rose to higher levels in EIA-positive groups. Plasma E levels rose
      with exercise and showed 4-fold increase in the EIA-negative group, whereas only
      1.5-fold increase of plasma E levels was observed in the EIA-positive group with
      poor recovery. From these findings, a possible contribution of sympathoadrenal
      hypofunction and a probable involvement of eosinophils in the pathophysiology of
      EIA have been suggested.

PMID- 8298716
TI  - Cobalt-chromium and nickel-chromium alloys for removable prosthodontics, Part 1:
      Mechanical properties.
AB  - PURPOSE: This investigation compared the mechanical properties of three base
      metal casting alloys (Vitallium2, Neoloy N [Regular], and Regalloy T) for
      removable partial denture (RPD) frameworks with those for two base metal RPD
      alloys (Vitallium, Jelenko LG) whose mechanical properties had been previously
      reported. MATERIALS AND METHODS: Plastic patterns with dimensions meeting ADA
      specification no. 14 requirements were used with appropriate casting investments
      to cast tensile test bars of the five alloys. Nine specimens of each alloy were
      loaded to failure, and the mechanical properties of modulus of elasticity, 0.1%
      yield strength, 0.2% yield strength, and tensile strength were obtained from five
      well-behaved load-elongation plots. Values of percentage elongation were also
      determined, along with Vickers hardness of the work-hardened alloys from polished
      cross-sections of fractured tensile specimens. The fracture surfaces for
      representative specimens of each alloy were examined with a scanning electron
      microscope. RESULTS: Although the measured values of mechanical properties
      generally agreed with those reported by the manufacturers, differences found for
      Vitallium and Jelenko LG with previous investigations suggest that there may have
      been some changes in alloy compositions and processing by the manufacturers. The
      investment burnout procedure adopted for the plastic patterns and the present
      casting conditions may also have affected the mechanical properties of some
      alloys. Two alloys, Jelenko LG and Regalloy T, had mean values of percentage
      elongation exceeding 10%, but caution is recommended for clinicians and dental
      laboratories when performing clasp adjustments with all five alloys because of
      the substantial work hardening that can occur. CONCLUSIONS: In general, all of
      the alloys met the requirements in ADA specification no. 14 for base metal RPD
      alloys. Further research will be necessary to determine the relationships between
      the mechanical properties, particularly yield strength, rate of work hardening
      and percentage elongation, and the clinical requirements for these alloys.

PMID- 8298717
TI  - The potential for bonding titanium restorations.
AB  - PURPOSE: The use of titanium for implants has shown the biological acceptance of
      the metal. Recently, methods of using titanium for restorations, crowns, and
      bridges have been introduced using both cast and spark erosion systems for
      fabrication. A potential also exists for using titanium for bonded (Maryland)
      bridges. MATERIALS AND METHODS: In this study, the potential for bonding titanium
      was investigated by cementing with various adhesives: (A) metal to metal, (B)
      metal to enamel, and (C) comparing with a known procedure of bonding nickel
      chromium. Truncated cones of pure titanium were fabricated with a 5-mm circular
      face for bonding to a larger titanium disc embedded in a plastic ring. A special
      jig was used to pull the bonded cone from the disc on an Instron tensile testing
      machine (Instron Corporation, Canton, MA). The resin-metal adhesives used were:
      (1) Infinity, (2) Metabond, (3) All-Bond 2, and (4) Panavia. These were compared
      with (5) nickel-chromium cones sandblasted and bonded to nickel-chromium with
      Panavia. Titanium cones were also bonded to human enamel with (6) Panavia and (7)
      Metabond. The 10 samples in each group were subjected to tensile force, and point
      of fracture was recorded. The data were subjected to an analysis of variance with
      a Scheffe F test at the 95% level of significance. RESULTS: The results of
      tensile forces in MPa were (1) Infinity, 28.1 +/- 3.6; (2) Metabond, 28.1 +/- 1;
      (3) All-Bond 2, 49.5 +/- 4.3; (4) Panavia, 57.9 +/- 3.1; (5) Panavia to nickel
      chromium, 42.9 +/- 6.6; (6) Panavia to enamel, 18.5 +/- 4.7; and (7) Metabond to
      enamel, 19.3 +/- 3.5. Titanium was most effectively bonded with All-Bond 2 and
      Panavia, with Panavia samples significantly better than Panavia to nickel
      chromium samples. CONCLUSIONS: It was concluded that titanium bonded restorations
      with certain adhesive cements were a definite possibility.

PMID- 8298719
TI  - A comparison of an accelerated technique for casting post-and-core restorations
      with conventional techniques.
AB  - PURPOSE: This project compares an accelerated technique for the casting of post
      and-core restorations with four traditional techniques. The accelerated technique
      uses two phosphate-bonded investments and the traditional techniques use a gypsum
      and a phosphate-bonded investment. The study measures and compares the
      differences between the seating of the casting and the seating of the acrylic
      resin pattern. The effects of the techniques on the fit of castings with and
      without a ferrule are also compared. MATERIALS AND METHODS: Six groups of 10
      castings were made from plastic patterns formed on a stainless steel test die. A
      different investment and/or burnout method was used for each group. Each group
      had two subgroups: ferruled and nonferruled. The fit of the plastic patterns was
      measured at two time intervals after forming, 2 weeks and 3 months. The patterns
      were invested immediately after the 3-month measurement, and the difference in
      fit of the castings was calculated. An ANOVA and Tuckey-Kramer test were done to
      determine the statistical validity. RESULTS: The seating of the patterns after 3
      months of storage was consistently worse than the 2-week measurements of fit. The
      ferrule and nonferrule patterns were not statistically different in seating.
      Measurement of the castings showed that the ferruled castings seated
      significantly worse than the nonferrule castings. The difference in the seating
      of the castings as compared with the patterns was considered clinically
      unacceptable, showing a range of 0.301 mm to 0.528 mm. The nonferrule castings
      showed a significant difference in seating among groups. The difference ranged
      from -0.099 mm to 0.322 mm. CONCLUSIONS: The castings of the ferrule subgroups
      were considered clinically unacceptable and were not analyzed for significance.
      Among the nonferrule castings, the group using a gypsum investment and
      conventional technique for investing and burnout but no ring liner showed the
      best seating. The accelerated technique was intermediate in seating with a
      difference of 0.148 mm from the seating of the patterns. This group was
      significantly different from the two best groups but not from the remaining three
      groups.

PMID- 8298718
TI  - Accuracy of irreversible hydrocolloid impression material mixed with disinfectant
      solutions.
AB  - PURPOSE: Irreversible hydrocolloid is capable of resisting contamination by
      viruses and saliva when the disinfectant iodine or the disinfectant chlorhexidine
      is added to the water being used to mix the material. This study investigates the
      accuracy of alginate impressions made with water to which either of the two
      disinfectants has been added. MATERIALS AND METHODS: A total of 30 casts were
      made from an impression of a master cast. Ten impressions were made using water
      according to the manufacturer's instructions, ten were made using water to which
      iodine had been added, and ten were made using water to which chlorhexidine had
      been added. A measuring microscope was used to measure three different dimensions
      on each cast. Each measurement was repeated three times, and the average was used
      to compute the mean and standard deviation for each measured dimension. The data
      were statistically evaluated using a one-way analysis of variance. RESULTS: There
      was no statistical difference in the accuracy of irreversible hydrocolloid
      impressions mixed with water or with either of two disinfectant solutions.
      CONCLUSION: Accurate casts can be obtained when either of the two disinfectants
      are incorporated into the alginate impression material.

PMID- 8298720
TI  - An investigation of the rheological properties of 10 vinyl-polysiloxane
      impression materials.
AB  - PURPOSE: The time required for 10 vinyl-polysiloxane impression materials to
      reach a viscosity of 5000 poise (Tcv) was estimated. This viscosity was selected
      based on previous work that suggested that an impression material might not be
      workable if its viscosity exceeded this limit. The effect of variations in the
      time of placement of the impression materials into a simulated oral-temperature
      environment was also studied. MATERIALS AND METHODS: The change in the viscosity
      of the impression materials was recorded with a viscometer at oral temperature.
      Impression materials were placed at either 20 seconds, 30 seconds, or 40 seconds
      from the start of mixing. RESULTS: There were statistically significant
      differences in Tcv among various impression materials. Variations in placement
      time significantly affected the Tcv of six impression materials. CONCLUSIONS:
      Knowledge of the viscosity change of an impression material is beneficial in the
      clinical selection of an impression material.

PMID- 8298721
TI  - Evaluation of polycaprolaitone custom tray material.
AB  - Custom impression trays are necessary for accurate impressions in fixed
      prosthodontics when using polysulfide impression materials. These custom
      impression trays are needed to provide for a uniform thickness of impression
      material to minimize distortion. Custom impression trays have historically been
      made from acrylic resin. New materials have been developed as alternatives to
      acrylic resin, and this study evaluates one product currently available that is
      composed of polycaprolaitone. This study evaluates the modulus of elasticity of
      polycaprolaitone as compared with acrylic resin, and also evaluates the amount of
      permanent deformation of the new material when placed under a load. The elastic
      modulus of polycaprolaitone was tested using three-point bending of specimens
      placed in a universal mechanical test system. The elastic modulus of the new
      material was found to be significantly lower than that of acrylic resin. The next
      test evaluated the amount of permanent deformation of the polycaprolatione
      material when specimens approximating the shape and size of custom impression
      trays were placed under a load. These trays were placed in a universal mechanical
      test system and differing loads were placed on them. Results showed that although
      the trays deformed at relatively low loads, all deformation was fully recovered
      within a clinically insignificant period of time (less than 30 seconds). From
      these experiments it was concluded that although the polycaprolaitone material
      has a lower modulus of elasticity and will deform under relatively low loads, the
      material recovers completely, and thus the deformation would not interfere with
      the clinical performance of polycaprolaitone as a custom tray material.

PMID- 8298722
TI  - Slant-lock implant-supported overdenture.
AB  - Slant-Lock overdentures, Class I: Division 3 prostheses, provide a stable and
      retentive prosthetic design for edentulous patients with osseointegrated
      implants. In patients who have moderate to severe atrophy of the edentulous
      ridge, the Slant-Lock overdenture provides additional support for the para-oral
      structures. The prostheses increase the ease of oral hygiene for the edentulous
      patient, can be constructed using conventional prosthodontic techniques, and are
      reasonably economical.

PMID- 8298723
TI  - Use of an axisymmetric finite element method to compare maxillary bone variables
      for a loaded implant.
AB  - PURPOSE: This study determined the effect of various bone models on the stresses
      and strains generated under occlusal loading of a dental implant. MATERIALS AND
      METHODS: A two-dimensional finite-element model was created for stress analysis.
      The geometric and elastic properties of a 3.8 x 10-mm Steri-Oss implant embedded
      in a segment of premaxilla were modeled. Computed tomography scanning of a dried
      maxilla half was used to determine representative geometry and density of this
      region. Material properties for bone were varied to simulate the following: all
      cancellous bone, cancellous bone with a thin (1.5-mm) crestal isotropic cortical
      layer, cancellous bone with a thick (3-mm) crestal isotropic cortical layer, and
      cancellous bone with a thick (3-mm) layer of transversely isotropic (orthotropic)
      cortical bone. RESULTS: Low stresses and high strains surrounded the fixture apex
      for the all-cancellous bone model. When a layer of cortical bone was added,
      higher crestal stresses and lower apical strains were observed. The thicker layer
      of isotropic cortical bone produced stresses at least 50% less than the thinner
      layer. The assumption of transverse isotropy (orthotropy) increased stresses and
      strains by approximately 25% compared with isotropic bone. CONCLUSIONS: Crestal
      cortical layer thickness and bone isotropy have a substantial impact on resultant
      stresses and strains. Clinical assessment of these parameters is recommended.

PMID- 8298724
TI  - Determination of the existence of hinge movements of the temporomandibular joint
      during normal opening by Cine-MRI and computer digital addition.
AB  - PURPOSE: The purpose of the first phase of this two-part investigation was to
      determine if the opening motion of the mandible could be illustrated and
      described using a dynamic imaging method. The purpose of the second phase of the
      investigation was to determine if a center of rotation would be discovered.
      MATERIALS AND METHODS: Five volunteer subjects, 2 female and 3 male, whose
      temporomandibular joints had previously been determined to be asymptomatic, were
      examined by magnetic resonance imaging (MRI) during opening from a standardized
      position. The serial static images were reconstructed by the MRI's computer in
      "cine mode" to simulate dynamic motion, similar to a motion picture. For the
      second phase, each patient's series of static images were digitally added and
      manipulated by a computer graphics program to locate the center of hinge motion.
      RESULTS: After reviewing the animated images recorded on videotape, three
      independent dentist observers confirmed that the opening movement of the mandible
      was initially rotational, followed by translation within the glenoid fossa. A
      center of rotation was calculated to be in the anatomic center of the condylar
      head of all of the subjects in this study. CONCLUSIONS: This study showed that
      opening dynamics of the mandibular condyle could be studied by cine-MRI and that
      an opening hinge axis appears to be located in the anatomic center of the
      condylar head.

PMID- 8298725
TI  - A one-appointment mouthstick appliance.
AB  - Quadriplegics rely on mouthstick appliances to perform a variety of tasks to
      establish more self-sufficiency. Present techniques to fabricate a quality
      mouthstick applicance requires professional expertise, time, and laboratory
      expense. A technique for providing an inexpensive, durable mouthstick appliance
      in one appointment is described.

PMID- 8298726
TI  - Fabricating crowns to fit existing removable partial dentures: an illustration of
      two techniques.
AB  - The prosthetic treatment of a structurally compromised abutment tooth supporting
      a removable partial denture may present a variety of restorative modalities.
      Ideally, a surveyed crown is made for the individual tooth, which is later
      followed by a new removable partial denture fit to the contours of the crown.
      Frequently, however, the removable partial denture is clinically acceptable, and
      remaking the prosthesis is not indicated. In these cases, the crown can be made
      to fit the existing removable partial denture. Fabricating crowns to fit existing
      removable partial dentures can be accomplished using a direct method, an indirect
      method, or combinations of these techniques. Direct techniques traditionally use
      acrylic resin and inlay wax intraorally to develop a custom pattern that captures
      the contours of the clasp assembly. Indirect techniques use a pick-up impression
      to allow the crown pattern to be waxed against the denture framework on a cast in
      the laboratory. Combination methods use either a direct-indirect or indirect
      direct approach. The direct-indirect method develops the preliminary resin
      pattern directly on the tooth and finalizes the contours in wax on a master cast.
      The indirect-direct technique initiates a crown pattern on a die and completes it
      either intraorally or on the die after the intraoral refinements. This article
      reviews the literature for methods of fabricating surveyed crowns under existing
      removable partial dentures. Additionally, two cases are presented that illustrate
      an indirect and combination direct-indirect technique for making the
      restorations.

PMID- 8298727
TI  - Adapting a dental surveyor to function in two planes.
AB  - Many bilateral distal extension removable partial dentures possess insufficient
      guidance to control their dislodgement. When such a situation is observed, the
      tips of retentive clasps must be located in both an occlusogingival and
      mesiodistal (away from the denture base area) undercut. The specific location can
      be identified with a dental surveyor that has been adapted to function in two
      planes. Details of the adaptation process and use of the surveyor are described.

PMID- 8298729
TI  - The race for places.

PMID- 8298728
TI  - Touch without hurt.

PMID- 8298730
TI  - Surviving the transition from university student to registered nurse.

PMID- 8298731
TI  - Writing and talking: getting the message across.

PMID- 8298732
TI  - Nursing and the law. Leaving medication unattended--where do you stand? How to
      handle uninvited casualties.

PMID- 8298733
TI  - Some variants of lethal neonatal short-limbed platyspondylic dysplasia: a
      radiological ultrasonographic, neuropathological and histopathological study of
      22 cases.
AB  - Data on twenty-two infants with lethal neonatal short-limbed platyspondylic
      dysplasia are reported. Thanatophoric dysplasia (TD) is the most frequent
      diagnosis in this group. TD combined with a cloverleaf skull (CS), has been
      variably classified. TD type 1 with curved femora is rarely combined with CS; TD
      type 2 with straight femora is almost always associated with CS. Other varieties
      of TD, known as 'Torrance', 'San Diego' or 'Luton' types, are separate entities.
      Apart from the differences in radiography and osteochondrohistology, the temporal
      lobe abnormalities seen in TD were absent in one of the cases of the 'Torrance'
      variety. There were also differences in the composition of the cartilage
      glycosaminoglycans between this case and TD. Nearly all of the cases of these
      different types mentioned in the literature, including those of this study group,
      have been sporadic and may result from new dominant mutations. Documentation and
      classification by full (postmortem) radiography and osteochondrohistology is
      essential for two reasons. It will be the foundation for the clinical geneticist
      to inform the parents about the risk of recurrence. It will also be the basis for
      a biochemical or molecular-biological classification in the near future.

PMID- 8298734
TI  - Previously unrecognized form of familial spondyloepiphyseal dysplasia tarda with
      characteristic facies.
AB  - Three sibs, the offspring of first cousin Pakistani parents, are reported with an
      apparently 'new' form of spondyloepiphyseal dysplasia with microcephaly, unusual
      facies and moderate developmental delay.

PMID- 8298735
TI  - Anorectal anomaly in Pfeiffer syndrome.
AB  - A Japanese girl with Pfeiffer syndrome is described. She has clinical and
      radiological manifestations typical of the syndrome. In addition, she had an
      imperforate anus not described previously in the syndrome. This seems to expand
      the phenotype associated with Pfeiffer syndrome or represent a new
      acrocephalosyndactyly syndrome.

PMID- 8298736
TI  - Dominant inheritance of microcephaly, short stature and congenital dislocation of
      the hips.
AB  - A family showing dominant inheritance of microcephaly, short stature, congenital
      dislocation of the hips and dysmorphic features is described. Affected
      individuals have malar hypoplasia, prominent nasal root, beaked nose, short
      philtrum and simple ears. This facial appearance is very similar to that in the
      family reported by Bawle and Horton in 1989.

PMID- 8298737
TI  - Multiple circumferential skin folds and other anomalies: a problem in syndrome
      delineation.
AB  - Three patients with multiple ring creases of the extremities are reported.
      Evidence to date points to aetiological heterogeneity. The skin folds may occur
      as an isolated abnormality or together with other patterns of malformation,
      making-up various syndromes that need to be further delineated. One type is
      associated with autosomal dominant inheritance. This striking abnormality usually
      resolves with time.

PMID- 8298738
TI  - The Schwartz-Jampel syndrome.
AB  - Three sibs with severe manifestation of Schwartz-Jampel syndrome are described.
      All died due to respiratory complications. Early diagnosis might help to prevent
      this complication. In addition to electromyography, skeletal radiographs can be
      helpful in establishing the diagnosis. The radiological manifestations of this
      syndrome are reviewed.

PMID- 8298739
TI  - Mullerian duct abnormalities and galactosaemia heterozygosity: report of a
      family.
AB  - Familial aggregates of Mullerian fusion anomalies (MFAs) and of Mullerian aplasia
      (MA) are rare. I report the case of a girl with MA and 'streak-like' ovaries,
      whose mother had a MFA. No similar mother-daughter pair appears to have been
      reported previously. The girl, mother, and maternal grandmother each have low
      galactose-1-phosphate uridyl transferase activities and are each heterozygous for
      the 'classic' galactosaemia allele. These findings support previous suggestions
      that MA may sometimes be related to abnormal galactose metabolism, and further
      suggest that, in some cases, MFAs may also be related to disordered galactose
      metabolism.

PMID- 8298740
TI  - EC syndrome in a girl with paracentric inversion (7)(q22.1;q36.3).
AB  - Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome associated with a
      paracentric inversion of chromosome 7 in a 2-year-old Japanese girl is reported.
      She had sparse and light-brown hair, bilateral cleft lip and palate, fused lower
      incisors, a pigmented skin lesion at the neck, accessory nipples, limited
      extension of elbow joints and bilateral ectrodactyly of hands and feet.
      Cytogenetic studies demonstrated a balanced inv(7)(q22.1;q36.3) in the patient
      and her father. The association of EEC syndrome and inv(7) in the patient
      suggested a putative locus of the EEC syndrome gene either at 7q22.1 or 7q36.3,
      although a coincidental occurrence of the two conditions is an alternative
      explanation. A comparison with reported karyotypes in patients with EEC or
      isolated ectrodactyly favoured 7q22.1 as the locus. A normal phenotype of the
      father in our family might reflect reduced penetrance of the EEC syndrome or,
      possibly, reduced expression of a maternally-derived allele of the EEC syndrome
      gene through a genomic imprinting mechanism.

PMID- 8298741
TI  - Kabuki make-up syndrome and hearing impairment.
AB  - In 1981, Niikawa et al. and Kuroki et al. independently described patients with a
      new syndrome consisting of mental retardation, postnatal growth deficiency and
      unusual facial features such as long palpebral fissures with eversion of the
      lateral one-third of the lower eyelids, arched and laterally sparse eyebrows and
      large prominent ears among other malformations. The condition has been called
      Kabuki make-up syndrome because the facial features in affected individuals
      resemble the make-up of the actors in a Japanese play: Kabuki. After the initial
      reports on Japanese individuals, the condition has been observed in several other
      patients of different ethnic origins including a few patients from this country
      (Kaiser-Kupfer et al., 1986; Pagon et al., 1986). We describe an additional 13
      year-old male patient with Kabuki make-up syndrome with possible implication of
      autosomal dominant inheritance from his mother. Interestingly, our patient also
      displayed hitherto unreported severe ossicular malformations resulting in
      significant hearing impairment.

PMID- 8298742
TI  - Unusual association of cerebral and renal abnormalities.
AB  - A 37-week male infant is reported with microbrachycephaly, micrognathia, a cleft
      palate, a small tongue and a patent ductus arteriosus. Postmortem examination
      revealed micropolygyria, absence of the olfactory bulbs and tracts, absence of
      the corpus callosum, marked hydrocephalus and abnormal midbrain structures and
      basal ganglia. The cerebellum was very small with an absent vermis. There was
      widespread impacted PAS-positive secretion distending the distal tubules within
      the cortex of the kidney, with scattered microcyst formation and occasional
      partly sclerosed glomeruli.

PMID- 8298743
TI  - Congenital malformation of the scalp and cranium after failed first trimester
      abortion attempt with misoprostol.
AB  - This study reports the occurrence of three cases of an unusual congenital
      malformation of the skull in neonates seen at a pediatric hospital during a five
      month interval in Fortaleza, Brazil. The prenatal history focused on the mothers'
      exposure to drugs during pregnancy. It was found that all mothers had taken
      misoprostol orally and/or vaginally in the first trimester of pregnancy to induce
      abortion. Other drugs taken during pregnancy included iron, vitamins and tetanus
      toxoid. There was no evidence of a family history of malformations, consanguinity
      or clinical infective illnesses.

PMID- 8298744
TI  - Severe prenatal infantile cortical hyperostosis (Caffey's disease).
AB  - We describe three cases of prenatal infantile cortical hyperostosis (Caffey's
      disease) from two families, all associated with maternal polyhydramnios. Case 1
      (family 1) was an early early neonatal death after delivery at 27 weeks
      gestation, case 2 (family 2) an intrauterine death at 33 weeks. Case 3 (family 2)
      had limited skeletal involvement and followed a course typical for Caffey's
      disease. Only six cases of prenatal Caffey's disease with extensive skeletal
      involvement have previously been described. Polyhydramnios was reported in all
      but one and the condition was lethal unless pregnancy reached term. To our
      knowledge cases 2 and 3 reported here represent the first description of Caffey's
      disease in which the prenatal lethal form was not sporadic.

PMID- 8298745
TI  - Rubinstein-Taybi syndrome: a history in pictures.
AB  - The Rubinstein-Taybi syndrome is a classical multiple congenital anomaly
      syndrome. The classical gestalt is striking and poses few diagnostic problems,
      but sometimes diagnosis is extremely difficult. In this paper the change in
      facial appearance of affected individuals is demonstrated, to improve insight
      into the evolution of the phenotype and to increase its diagnostic potential.

PMID- 8298746
TI  - Is prevention of food allergy worthwhile?
AB  - Several studies performed in high-risk babies have demonstrated a significant
      reduction in the prevalence and severity of atopic diseases with dietary and
      environmental manipulations. It has been demonstrated that prolonged breast
      feeding and the avoidance of cow's milk, eggs and fish during the first three
      months of lactation significantly decrease both the prevalence and the severity
      of atopic disease up to the age of 5 years. We have shown a significant reduction
      in both the prevalence and the incidence of atopic dermatitis, food allergy and
      asthma in high-risk children followed up to the age of 5 years who received
      preventive dietary (prolonged breast-feeding, cow's milk- and egg-free diet to
      the nursing mothers, supplementation with a soya formula containing sucrose when
      breast milk was not available, delayed weaning) and environmental measures (no
      smoking and no pets in the house, measures for the elimination of mites, etc.).
      However, occasionally, breast-fed infants may experience allergic sensitization
      to food antigens ingested by the mother during lactation. The factors that
      determine which infants will develop sensitization to food antigens in breast
      milk are not fully understood. The genetic predisposition to IgE-mediated
      hypersensitivity reactions is certainly a prerequisite; however, properties of
      human milk, such as immune characteristics, may play a role in the phenotypic
      expression of sensitization. Our studies suggest that the abnormally low levels
      of the long-chain polyunsaturated derivatives found in infants at risk of atopy
      are unlikely to be corrected by breast-feeding and may explain the contradictory
      results from studies on the effectiveness of breast milk against the development
      of atopic dermatitis.

PMID- 8298747
TI  - Abnormal migratory activity of peripheral neutrophils from asthmatic patients and
      its modulation by inhaled glucocorticoids.
AB  - In order to investigate if bronchial asthma is associated with enhanced markers
      of activation in peripheral neutrophils, the migratory capacity of neutrophils in
      venous blood was measured by means of the Boyden chamber technique in 29 subjects
      with bronchial asthma of differing severity. Random migration (random motility),
      but not locomotion toward 10% Escherichia coli supernatant as chemoattractant
      (chemotaxis), was increased in asthmatic subjects with respect to 11 normal
      subjects (98 +/- 20 microns vs. 85 +/- 6 microns; p < 0.05). When asthmatic
      subjects were subdivided into groups of different disease severity, subjects with
      mild and mild to moderate asthma showed significantly higher values for random
      motility and chemotaxis than normal subjects; on the other hand, subjects with
      more severe disease showed the lowest values for migratory activity. No
      correlation was found between migratory activity and clinical findings of asthma,
      except for baseline FEV1 (% of the predicted value), which showed a slight but
      significant positive correlation with chemotaxis (r = 0.44, p < 0.05). Subjects
      with atopic or occupational asthma had higher values for migratory activity than
      subjects with nonallergic asthma. Thirteen asthmatic subjects repeated all
      evaluations after 1 month of treatment with high doses of inhaled glucocorticoids
      (beclomethasone dipropionate 1500 micrograms/day). Random motility (95 +/- 24
      microns vs. 75 +/- 15 microns; p < 0.05) and chemotaxis (130 +/- 22 microns vs.
      105 +/- 25 microns; p < 0.05) were significantly reduced after treatment, as well
      as the symptom score; on the other hand, symptom score but not bronchial
      hyperresponsiveness to methacholine challenge significantly changed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8298748
TI  - Cutaneous sensitivity to six mite species in asthmatic patients from five Latin
      American countries.
AB  - The prevalence of positive skin prick tests to the mite species Dermatophagoides
      pteronyssinus, D. farinae, Blomia tropicalis, Chortoglyphus arcuatus,
      Lepidoglyphus destructor and Aleuroglyphus ovatus was determined in 297 asthmatic
      adults and children living in seven cities of five Latin American countries. A
      standardized protocol and a common battery of extracts were used at each site.
      The mean wheal diameters were measured after 15 min, and those > or = 3 mm were
      considered positive. Sensitization to D. pteronyssinus varied from 60.7% in
      Cartagena to 91.2% in Sao Paulo; to D. farinae from 53.3% in Cordoba to 97.2% in
      Caracas; to A. ovatus from 26.6% in Bogota to 71.2% in Sao Paulo; to B.
      tropicalis from 46.5% in Mexico City to 93.7% in Sao Paulo; to C. arcuatus from
      33.3% in Mexico City to 75% in Sao Paulo; and to L. destructor from 30% in Mexico
      City to 76.2% in Sao Paulo. This study reported the results of skin test
      sensitivities in both children and adults. The studies from Sao Paulo and Cordoba
      were confined to children and thus could be compared; there was a significantly
      higher prevalence of cutaneous sensitivity to mite allergens in the children of
      Sao Paulo than in those of Cordoba (p < 0.001 for all mite species). Cutaneous
      sensitivity to mite allergens is very common in young and adult asthmatics in
      Latin America, in areas both at sea level and at high altitudes. Environmental
      control measures should be reinforced in the treatment of asthmatics in Latin
      America.

PMID- 8298749
TI  - Annual, daily and diurnal variations in pollen from Olea europaea L. in the
      atmosphere of Granada (Spain).
AB  - The allergenic capacity of Olea europaea L. pollen is very important in several
      cities of the southern Iberian Peninsula, producing most pollinoses diagnosed in
      these cities. We have carried out a study on the annual, daily and diurnal
      variations in pollen from O. europaea in the atmosphere of Granada (Spain) during
      4 consecutive years. Samplings were carried out with the aid of a Burkard spore
      trap. Very low levels of Olea pollen grains were first detected in the atmosphere
      from the end of April. Pollen levels peaked in May and June, and started to
      decrease from the last days of June and in July. Pollen in the atmosphere is
      related to meteorological parameters: temperature has a positive influence on
      pollinization and rainfall produces a negative effect. The diurnal variation
      pattern of pollen grain concentrations was quite homogeneous throughout the
      study, featuring an important increase around midday and a moderate decrease in
      the first hours of the morning and in the late evening.

PMID- 8298750
TI  - Granulocyte migration in vivo and in vitro in healthy children of parents with
      aspirin-sensitive asthma.
AB  - The test of granulocyte migration in vitro and in vivo was carried out in 30
      healthy children who had at least one parent with aspirin-sensitive asthma. A
      defect in granulocyte migration was demonstrated in children with both parents
      having aspirin-sensitive asthma.

PMID- 8298751
TI  - Immunoglobulin-secreting cells in primary immunodeficiency diseases.
AB  - To assess immunoglobulin production in vivo, the numbers of immunoglobulin
      secreting cells were measured in uncultured peripheral blood mononuclear cells
      (PBMCs) of patients with primary immunoglobulin deficiency. The numbers of
      immunoglobulin-secreting cells were found to be variable, and they were well
      correlated with the serum concentrations of all three major immunoglobulin
      classes. Our results suggest that measurement of immunoglobulin-secreting cells
      in PBMCs is useful in the assessment of the ability to produce immunoglobulin in
      vivo.

PMID- 8298752
TI  - Changes in total serum IgE concentrations after splenectomy.
AB  - In addition to allergic diseases, there are other disorders that can be
      accompanied by increased levels of total serum IgE. It has been demonstrated that
      splenectomy can alter the serum concentrations of other immunoglobulins. The aim
      of this study was to examine the concentrations of total IgE in the serum of
      patients splenectomized as a result of abdominal trauma but with no associated
      disease. Our results show that the average concentrations in the serum of
      patients were significantly higher that in the control group. Furthermore, in a
      large number of patients, the concentrations were above the normal limit set for
      the nonatopic Spanish population. These results suggest that splenectomy can
      alter the regulation of IgE concentrations. Since total IgE is usually determined
      for diagnostic purposes, it is useful to be aware of this anomaly when dealing
      with splenectomized patients in order to interpret correctly the laboratory
      analyses.

PMID- 8298753
TI  - Spring pollen and related allergies in southern Spain.
AB  - Over the last 10 years, there has been an increase in pollen allergies throughout
      Europe; this trend is clearly reflected in this study carried out in Cordoba
      (southern Spain) over 7 consecutive years, which recorded important increases in
      the concentrations of certain pollen types of particular interest in this city,
      together with an increase in the number of patients with pollinosis visiting the
      Allergy Unit at Cordoba's Reina Sofia University Hospital. The purpose of this
      study was to ascertain whether these two trends were related. Sampling was
      carried out from 1984 to 1990, using a Burkard spore trap placed at a height of
      approximately 15 m on a building situated in the city center. The trend towards
      an annual increase in the concentration of pollen grains was positive in all
      cases, although very slight for Quercus and very marked for Olea europaea.
      However, a different pattern of behavior was recorded with respect to the
      correlation between pollen concentration and cases of pollinosis, a correlation
      which varied according to taxa.

PMID- 8298754
TI  - [Attitude concerning acting methodically. A study in the Maastricht Academic
      Hospital].

PMID- 8298755
TI  - [Reliability, validity and usefulness of the TAS (therapeutic activity score).
      For patient classification in an intensive care unit].

PMID- 8298756
TI  - [Nursing diagnosis].

PMID- 8298757
TI  - [Influence of level of competence on quality of caregiving in complex nursing
      care situations].

PMID- 8298759
TI  - [Resident differentiation in the nursing home].

PMID- 8298758
TI  - [Pain anamnesis list for district nurses--the extramural pain questionnaire].

PMID- 8298760
TI  - [Current financing of health care].

PMID- 8298761
TI  - [Impending shortage of nursing personnel].

PMID- 8298762
TI  - [Decision making in nursing. A literature review of the manner in which nurses
      make a diagnosis].
AB  - In clinical practice professional nurses appear to make different judgments
      regarding particular nursing situations. Assuming that it is desirable that
      nurses, confronted with the same situation, make the same decisions, it is
      important to gain insight into the way decisions are made. The purpose of this
      literature review is to summarize what is already known about decision-making in
      nursing. It appears that most of the texts on decision-making in nursing are
      based on a general model on decision-making: the information-processing model.
      Factors influencing decision-making processes are discussed. Finally, an overview
      is given of research on decision-making in nursing.

PMID- 8298763
TI  - [COPD home visit with children. Comparison of the quality of various models].
AB  - This article reports on the quality and efficiency of asthma home visits paid by
      nurses. These home visits were part of a research project on out-of-hospital
      asthma care for children in the province of Noord-Holland (the Netherlands). In
      this project we compared three different models of out-of-hospital nursing care
      for asthmatic children: a. care delivered by local generalist community nurses;
      b. care delivered by local community nurses who are partly specialized in asthma
      care; c. care delivered by specialist hospital-based asthma nurses. A total of
      120 children with asthmatic complaints were randomly assigned to one of those
      models. Based on literature study and interviews with experts in the field,
      criteria were developed for quality and efficiency of asthma home care for
      children. Interviews with the parents of the children involved in the project
      provided information on the content and the duration of the home visits as well
      as on their evaluation on the care received. One of the (unexpected) findings was
      that in all three models of care very little attention was given to important
      aspects such as prescribed medication and the use of inhalers and psychosocial
      factors that made be related to the complaints. Previous experience of the nurses
      in asthma home visits proved to be an important aspect of the quality of care.

PMID- 8298764
TI  - [Tasks of caregivers in a nursing home. A study of tasks and reactions of
      caregivers].
AB  - This paper describes a study on the task perceptions of enrolled nurses in a
      nursing home and the relationships between task perceptions and reactions such as
      burnout, job satisfaction, experienced job significance and absenteeism (Harmsen,
      1991). In our study a comparison is made on the one hand between the task
      perceptions of three different functions in the nursing home, namely the unit
      heads, the graduated and the student nurses, and on the other hand between the
      task perceptions of enrolled nurses working on two types of wards, namely somatic
      and psycho-geriatric wards. Concerning the relationships between task perceptions
      and reactions, the results of our study show that activities regarding the
      'nursing record', the 'nursing report', the 'stimulation of self-care' and
      'social contact' usually have a positive relationship with the experienced job
      significance of enrolled nurses. On the contrary, activities concerning daily
      care are evaluated negative. Finally, tasks in the area of 'instrumental
      activities', 'caring for the dying' and 'caring for the privacy of the client'
      appear to have positive as well as negative effects.

PMID- 8298765
TI  - Measures for use in asthma clinical research. Overview of the NIH workshop.

PMID- 8298766
TI  - Clinical and symptom measures.
AB  - We present a review of specific health status measures, including symptoms,
      physical examination, and laboratory tests (exclusive of lung function tests), in
      terms of their suitability for assessing the presence and severity of asthma in
      epidemiologic and clinical research. We focus on the validity, reliability, and
      responsiveness to clinical intervention of these measures. Several adult
      questionnaires designed for epidemiologic research include questions on asthma
      and wheezing that have demonstrated repeatability and validity against concurrent
      measurements of nonspecific airway responsiveness. The International Union
      Against Tuberculosis Bronchial Symptoms Questionnaire was designed specifically
      to detect asthma and airway hyperresponsiveness in adult populations, and its
      reliability and validity have been well documented. A childhood questionnaire
      developed by Australian investigators has been demonstrated to provide
      information on asthma and wheezing that is reliable and valid against the
      criterion of concurrently measured nonspecific airway responsiveness. Although
      suitable for epidemiologic research, these questionnaires do not provide
      sufficient data on the severity of current asthma symptoms (aspects of which
      include intensity, duration, and frequency of symptoms) to be useful for clinical
      research involving subjects with established asthma. Many different methods of
      obtaining and analyzing symptom data have been used in clinical trials, but these
      have not received the methodologic scrutiny that allow the recommendation of a
      "best" approach for evaluating symptoms in clinical trials of interventions for
      asthma. The use of daily symptom diaries in short-term drug trials is common, but
      the optimal symptom-reporting interval for such studies has not been established.
      Similarly, a particular approach to integrating different symptoms (wheeze,
      dyspnea, cough, sputum) and the different aspects of these symptoms (intensity,
      duration, frequency) cannot be recommended on the basis of available data.
      Physical examination findings have little utility as asthma outcome measures
      because they may be normal between symptom episodes, they have relatively poor
      interobserver reliability, and they are relatively poor predictors of the outcome
      of emergency room visits for asthma. The finding of an elevated arterial PCO2 has
      utility as an indicator of a severe asthma attack, but arterial blood gas
      measurements have little other utility as asthma outcome measures. The chest
      radiograph is generally normal in patients with asthma and therefore not useful
      as an asthma outcome measure.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8298767
TI  - Measures of life quality, role performance, and functional status in asthma
      research.
AB  - Recently a consensus has emerged that health care research should address
      outcomes important to patients, especially quality of life, role performance, and
      functional status. The assessment of such outcomes is beset by conceptual and
      methodological difficulties that may be especially problematic for asthma.
      Nevertheless, several broad conclusions may be drawn about the use of measures of
      these outcomes in asthma research. Asthma usually is reasonably well controlled
      if patients are moderately adherent to their recommended regimens. Consequently,
      the beneficial impacts of interventions are likely to be small, and large samples
      are required to detect them. Outcome assessment should combine asthma-specific
      measures with generic measures applicable to a variety of conditions. Generic
      measures aimed at severely debilitating disease are less appropriate than
      measures designed for use in the general population. Asthma-specific measures
      should emphasize the incidence and impact of such symptoms as coughing, wheezing,
      sputum production, and shortness of breath. Current procedures for computing
      utility scores and cost-benefit ratios based on them have serious measurement
      limitations, and use of such scores should be postponed until those limitations
      are overcome. These assessment issues should be addressed separately for adults
      and children.

PMID- 8298768
TI  - Treatment regimen and side effects of treatment measures.
AB  - The severity of asthma can be judged by many features, including the need for
      medication and associated side effects. Since asthma has both acute and chronic
      characteristics, therapeutic regimens should be valuable as an instrument to
      define disease severity and the consequence of intervention. However, because of
      the variability of asthma severity within each patient, medication quantitation
      as an index of asthma severity is not without difficulty and limitation.
      Furthermore, the philosophy of asthma therapy has undergone changes over the past
      decade. Previously, anti-inflammatory therapy was reserved for only the most
      severely ill patients. Now, inflammation is recognized as a critical component of
      asthma, and all patients with active asthma (other than mild symptoms) are
      recommended to use anti-inflammatory therapy. Although there is little published
      experience with treatment regimens as an index of disease severity, those that
      have been used have found validity and reproducibility with this approach. In
      this paper, a scoring approach to medication use is recommended. Medication is
      classified into bronchodilator (beta-agonists, theophylline, and anticholinergic)
      or anti-inflammatory (corticosteroid and cromolyn sodium). Medication scores are
      given on either a per-use or a new-dosage basis. Furthermore, the eight
      medications are stratified according to potency (i.e., inhaled corticosteroid <
      oral corticosteroid < parenteral corticosteroid). From this approach, the
      severity of an individual patient's asthma can be quantitated, and this value can
      serve as one instrument to assess disease severity.

PMID- 8298769
TI  - Management of asthma by patients and families.
AB  - This paper focuses on assessment of asthma-management outcomes resulting from
      interventions for patients. Noted is the need to design both programs and
      evaluations that reflect a theoretical understanding of behavior change. For
      purposes of illustration, the theoretical construct of self-regulation is used.
      It is posited that individuals are predisposed to take action to handle asthma
      problems by virtue of internal (knowledge, attitudes, beliefs) and external
      (models of behavior, technical advice and service, money, etc.) factors. Through
      processes of self-regulation--that is, the ability to observe, make judgments,
      and react to one's own behavior--individuals learn which management strategies
      (prevention, symptom management, negotiation, and communication) work for them.
      If these management strategies are effective, one would expect certain outcomes:
      the patient's personal goal will be reached; physiologic and psychological health
      status will be maintained or improved; and health care use will be appropriate. A
      range of good studies of patient behavior related to asthma management and of
      interventions to enhance behavior are available, and provide some evidence that
      these outcomes can be attained. A solid foundation for the development of more
      sophisticated and refined self-management assessment measures is available.
      Objective measures have been used to verify behavior in two or three research
      projects. Although objective measures are costly and can be cumbersome to
      administer, more effort to develop and use such measures is needed. Testing of
      the reliability and validity of existing patient-management measures has been
      perfunctory, and greater attention, especially to the validity of measures, is
      needed. Six recommendations for better measurement are made.

PMID- 8298770
TI  - Measuring adherence to asthma medication regimens.
AB  - The failure of patients to adhere to physician-prescribed regimens, either
      pharmacologic or behavioral, has been well documented in medical literature. Poor
      adherence to asthma medication regimens has been repeatedly demonstrated in both
      children and adults, with rates of nonadherence commonly reported from 30 to 70%.
      Medication regimens for asthma care are particularly vulnerable to adherence
      problems because of their duration, the use of multiple medications, and the
      periods of symptom remission. The clinical effects of this nonadherence by
      asthmatic patients can include treatment failure, unnecessary and dangerous
      intensification of therapy, and costly diagnostic procedures, complications, and
      hospitalizations. Although the measurement of adherence is an important component
      of both medical and behavioral interventions to control asthma, relatively little
      research has directly addressed the reliability and validity of the measures most
      widely used to assess asthma medication compliance. This review will discuss
      methods and issues in the measurement of adherence in general, and where
      available, measures that have been specifically used in evaluating adherence to
      asthma medication. Common measures used to assess compliance with asthma
      medications include direct measures, which confirm the use of medication by
      assaying it in blood, urine, or saliva, or which confirm the to use a medication,
      such as observed skill in using a metered dose inhaler. Indirect measures infer
      use with varying degrees of reliability, by use of clinical judgment, self
      report/asthma diaries, medication measurement, and electronic medication
      monitors. The uses and limitations of these measures will be discussed.

PMID- 8298771
TI  - Uses and limitations of mortality and health care utilization statistics in
      asthma research.
AB  - Mortality and health care utilization (HCU) statistics for asthma reflect both
      the acute and chronic aspects of this condition. We present a conceptual model
      that incorporates this dichotomy and also distinguishes between measures of
      disease occurrence (e.g., incidence and prevalence) and measures of disease
      management. We also discuss the use of mortality and HCU statistics in the
      literature, review their limitations and advantages, and make a number of general
      recommendations for their use.

PMID- 8298772
TI  - Physiologic measures: pulmonary function tests. Asthma outcome.
AB  - When the effectiveness of asthma interventions are evaluated in the research
      setting, the physiologic manifestation of asthma-variable airways obstruction-is
      always objectively measured by some of the following pulmonary function tests:
      (1) Baseline spirometry gives a highly accurate "snapshot" of asthma severity and
      the degree of airways obstruction. The FEV1, derived from spirometry, is the most
      reproducible pulmonary function parameter and is linearly related to the severity
      of airways obstruction. There are no contraindications for the test, spirometers
      are widely available at reasonable cost, and methods and result interpretation
      are comprehensively standardized. (2) The post-bronchodilator FEV1 measures the
      best lung function that can be achieved by bronchodilator therapy on the day of
      the visit and therefore is a more stable measure in asthmatics than comparing
      visit-to-visit baseline FEV1. Although a positive acute response to
      bronchodilator helps to confirm the diagnosis of asthma, the degree of
      bronchodilator reversibility from visit-to-visit (change in reversibility) is not
      a useful index of asthma outcome. (3) Airway responsiveness (bronchial challenge)
      measures the degree to which an individual withstands nonspecific stimuli that
      trigger asthmatic attacks. The methacholine challenge test is safe and requires
      less than an hour, but it requires more technical skill than baseline spirometry
      and is contraindicated in some situations. (4) Ambulatory monitoring, using peak
      flow meters or hand-held spirometers, provides multiple measurements of the
      degree of obstruction for days to weeks in the patient's natural setting. PEF
      meters are very inexpensive and almost all asthmatics can use them, but PEF
      results are less reliable than the FEV1. The often asymptomatic obstruction of an
      asthmatic has both short-term (within a day and day-to-day) and longer-term
      variations that are triggered by naturally occurring stimuli. These changes are
      measured by PEF lability but not by spirometry during clinic visits. (5) Other
      pulmonary function tests, such as absolute lung volumes and airways resistance,
      may provide confirmatory data, but the instruments are large, expensive, and
      technically demanding. The results of all the above pulmonary function tests are
      significantly correlated with each other and with symptom scores and medication
      use in large groups of patients with widely varying degrees of asthma severity.
      Since a "gold standard" with which to measure asthma severity does not currently
      exist, all of these tests contribute an additional amount of unique information
      when measuring asthma outcome in a clinical trial.

PMID- 8298774
TI  - Anatomical studies and five years clinical experience with the distally based
      medial fasciocutaneous flap of the lower leg.
AB  - Anatomical dissections, dye studies and clinical experience with the highly
      versatile inferiorly based medial lower leg fasciocutaneous flap, originally
      described by Amarante et al., have been described. Clinical uses include cover of
      the lower half of the tibia, foot and tendo achilles. Variations of the flap are
      described. The flap has been used in 42 clinical cases with only 2 failures and 2
      partial failures. The dissection of the flap is quick and simple and the
      perforators reliable. The flap has obviated the need for a free flap in many of
      the cases, thus increasing the turnover in a busy unit. Dye injection studies and
      clinical experience have alerted us to the random nature of the flap in the
      proximal segment as described by Amarante. In high risk patients we modify the
      design.

PMID- 8298773
TI  - Associated injuries in facial fractures: review of 839 patients.
AB  - Patients with facial trauma may have associated injuries requiring immediate or
      specialised attention. This paper reports the incidence and nature of significant
      associated neurosurgical, ocular, spinal, torso and extremity injuries in facial
      fracture patients treated by the Department of Plastic and Reconstructive Surgery
      from June 1989 to June 1992. Of 839 patients treated during the period, 95
      patients (11.3%) sustained significant concomitant injuries outside the facial
      skeleton. There were 45 (5.4%) patients with associated neurosurgical injuries,
      33 (3.9%) with ocular injuries, 8 (0.9%) with spinal injuries, 16 (1.9%) with
      injuries of the torso, and 62 (7.4%) with injuries of the extremities. The
      spectrum of the injuries is presented. Most neurosurgical injuries are a result
      of focal impact and the intervention required is related mainly to local fracture
      management and the repair of dural tears. The risk of significant ocular injury
      is highest when the fracture involves the orbit. Injuries of the spine, torso
      (chest, abdomen, pelvis), and limbs were seen mainly in road trauma patients.

PMID- 8298775
TI  - Double V-Y advancement flaps in the reconstruction of skin defects of the
      anterior lower limb.
AB  - A double V-Y advancement flap based upon a vertical subcutaneous pedicle was
      assessed for reconstruction of moderate sized defects of the anterior lower leg.
      The technique is described and the results of a retrospective analysis of
      thirteen cases are given. The procedure has proven to be a reliable alternative
      means of providing skin cover in this area.

PMID- 8298776
TI  - Defining medical ethics.

PMID- 8298777
TI  - The deep venous system and reverse flow flaps.
AB  - The deep venous system of the upper and lower extremities was injected with a
      lead oxide mixture in 2 fresh human cadavers, dissected, radiographed and the
      sites of the venous valves located. These studies confirmed that the macrovenous
      connections between the venae comitantes of the distributing arteries were
      insufficient in number to bypass the venous valves in conventional, distally
      based reverse flow flaps (e.g. radial, ulnar, peroneal) but revealed an
      alternative microvenous interconnecting pathway which surrounds the artery as the
      venae arteriosa. This pathway was investigated in a series of distally based
      reverse flow saphenous flaps in dogs, comparing flaps where the microvenous
      connections were left intact (non-skeletonised) with those where these vessels
      were disconnected with the operating microscope (skeletonised). All non
      skeletonised flaps survived subtotally or totally whereas total necrosis was
      observed in 70% of the skeletonised flaps. Finally a series of haemodynamic
      studies was performed to test valve competency including extrinsic pressure on
      the valves. It is concluded that the macrovenous and microvenous pathways,
      coupled with the variable anatomy of the venous valves, are major factors in
      determining the survival of reverse flow flaps.

PMID- 8298778
TI  - Cutaneous blood flow in the free TRAM flap.
AB  - According to clinical studies there are fewer circulatory complications with the
      free TRAM flap than with the pedicled TRAM flap. In this haemodynamic study, we
      measured perioperative cutaneous blood flow in 11 free TRAM flaps with laser
      Doppler flowmetry (LDF) and transcutaneous oxygen tension (ptcO2). We also
      studied 4 pedicled TRAM flaps with an additional microvascular anastomosis. Our
      results suggest that skin blood flow in the free TRAM flap is superior compared
      to our previously presented results of the pedicled TRAM flaps, and also superior
      to pedicled TRAM flaps with additional microvascular anastomoses of the inferior
      epigastric vessels to "supercharge" them.

PMID- 8298779
TI  - A study of topical and systemic prostaglandin E1 and survival of experimental
      skin flaps.
AB  - A study has been undertaken to investigate Prostaglandin E1 administration
      procedure for improving flap survival. Whether the drug was administered
      continuously or transcutaneously using a silicone gel drug delivery system; or
      was topically injected into the critical zone of the flap; or was
      intraperitoneally administered intermittently over an hour after surgery a
      statistically significant improvement of flap survival occurred (P < 0.01,
      Student's t-test). However, no improvement of flap survival was seen when the
      drug was administered only once intraperitoneally immediately after flap
      elevation, although administered doses of the drug in those rats was equal to the
      doses in the rats which received intermittent administration of the drug
      intraperitoneally over an hour after surgery.

PMID- 8298780
TI  - Epidemiology of facial clefts in the central province of Saudi Arabia.
AB  - A pilot study collecting data both retrospectively and prospectively covering a
      span of 4 years (January 1989 to December 1992) was carried out at King Fahd
      Specialist Hospital, Al-Gassim, Saudi Arabia. The aim was to study the
      epidemiology of facial clefts in the exclusively Saudi population. A total of 137
      cases were studied. This study gives the highest reported incidence of clefts
      (2.19 per 1000 live births) with some distinct differences in the pattern of
      clefts as compared to other documented studies.

PMID- 8298781
TI  - The modified Z-plasty for unilateral cleft lip repair.
AB  - In 1965 Davies described a Z-plasty technique for the repair of a unilateral
      cleft lip. The technique has been modified so that the scars are more
      aesthetically placed and the orbicularis muscle correctly aligned. A prospective
      study was performed comparing the results of this modified Z-plasty with the
      rotation advancement repair. Twelve patients had a modified Z-plasty and 10 a
      rotation advancement repair. The modified Z-plasty compares favourably with the
      rotation advancement technique for the repair of a unilateral cleft lip. In
      particular, the incidence of asymmetry of lip height was greater in the rotation
      advancement group.

PMID- 8298782
TI  - Do babies require arm splints after cleft palate repair?
AB  - Traditionally, arm restraints are used in children after cleft surgery to prevent
      traumatic disruption of the repair. A questionnaire amongst consultant plastic
      surgeons in the UK that restraints are in common use. However, a prospective
      randomised trial of 46 children having primary cleft palate repair showed that
      arm splints did not decrease the incidence of oronasal fistulae. Six of 21
      children who had arm splints in the postoperative period and 5 of 25 who did not
      have splints developed an oronasal fistula. We have therefore abandoned the use
      of arm splints after cleft palate repair.

PMID- 8298783
TI  - Mandibular lengthening by gradual distraction: analysis using accurate skull
      replicas.
AB  - Bone lengthening in the upper and lower extremities by gradual distraction has
      become an accepted procedure. We have used an extraoral device to lengthen the
      mandible in four patients with unilateral mandibular hypoplasia. Using an
      accurate skull replica, the proposed corticotomy line, intended direction of
      lengthening, and appropriate position for the screws were determined. Following
      distraction, a significant increase in the dimensions of the affected mandible
      was obtained in each case. In this series, accurate skull replicas proved very
      useful for defining the anatomy, for surgical simulation and for pre- and
      postoperative evaluation.

PMID- 8298784
TI  - Preliminary report: intratumoral ligation as a salvage procedure for the
      management of life-threatening arteriovenous malformations.
AB  - Arteriovenous malformations are rare, high flow vascular anomalies which are
      frequently difficult to manage. Treatment options include embolisation and/or
      surgery, the latter ranging from proximal ligation (now discredited) through to
      radical resection. The Popescu technique of intratumoral ligation was used to
      treat 3 patients with massive, life-threatening arteriovenous malformations which
      were considered unsuitable for embolisation therapy or surgical resection. The
      main complications experienced were soft tissue swelling and necrosis, transient
      peripheral nerve entrapment and haemorrhage. The preliminary results have been
      encouraging and suggest that effective palliation and control can be achieved; 1
      patient has no clinically demonstrable recurrence nearly 3 years after surgery.

PMID- 8298785
TI  - Botulinum A chemodenervation: a new modality in cerebral palsied hands.
AB  - Botulinum A chemodenervation of the Adductor Pollicis muscle for the treatment of
      the thumb-in-palm deformity in cerebral palsied hands is presented as a new
      therapeutic option. Early results of a clinical trial in five hemiparetic
      Cerebral Palsied (C.P.) children are assessed using a prospective nontrialist
      biased study design based on an independent panel assessment of pre- and post
      intervention photographic and videotaped records of hand function and appearance,
      in combination with grip dynamometry and goniometry. All cases are shown to
      improve in terms of both function and appearance with results approaching
      statistical significance (p = 0.06) when assessed by the Wilcoxon's matched-pairs
      signed rank test, despite the small study group. The modality is shown to be
      simple, safe and effective over the period reported (229 days). The benefit is
      sustained beyond the period of muscle paresis and ongoing long term follow-up
      will document the need for, and timing of, reinjection.

PMID- 8298786
TI  - Postoperative cooling enhances composite graft survival in nasal-alar and
      fingertip reconstruction.
AB  - A simple method using ice-water and aluminium foil for enhancing composite graft
      survival is reported. Cooling the entire recipient site retards cellular
      degeneration in the graft until neovascularisation occurs. The success of this
      technique in nasal reconstruction using auricular chondrocutaneous tissue and
      nonmicrosurgical fingertip reattachment is presented. The potential application
      to thicker skin grafts is also discussed.

PMID- 8298787
TI  - Localised varicosities in a 39-year-old tissue transfer to the lower limb.
AB  - The typical symptoms and signs of venous stasis disease with ulceration were
      found in a lower limb reconstruction within the tissues of a tube pedicled
      abdominal wall tissue transfer, performed 39 years previously. Varicosities were
      found on venogram to be limited to the donor tissue only.

PMID- 8298788
TI  - A self-retaining nasal splint.

PMID- 8298789
TI  - Necrotising fasciitis.

PMID- 8298790
TI  - Characterization of the 5-HT4 receptor mediating tachycardia in piglet isolated
      right atrium.
AB  - 1. In order to explore whether 5-HT4 receptor subtypes exist, we have
      characterized further the 5-HT4 receptor that mediates tachycardia in the piglet
      isolated right atrium. All experiments were carried out in the presence of
      propranolol (400 nM) and cocaine (6 microM). We used tryptamine derivatives,
      substituted benzamides and benzimidazolone derivatives as pharmacological tools.
      2. Tachycardia responses to 5-hydroxytryptamine (5-HT) were mimicked by other
      tryptamine derivatives with the following order of potency: 5-HT > 5
      methoxytryptamine alpha-methyl-5-HT = bufotenine bufotenine > 5
      carboxamidotryptamine = tryptamine (after treatment with pargyline) > 5-methoxy
      N,N-dimethyltryptamine > 2-methyl-5-HT. 3. The substituted benzamides were all
      partial agonists relative to 5-HT except (-)-zacopride which was a full agonist.
      The stimulant potency order was renzapride > cisapride = (-)-zacopride >
      metoclopramide > (+)-zacopride. 4. The benzimidazolone derivatives had
      contrasting effects. BIMU 8 (endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3
      dihydro-(1-methyl(eth yl- 2-oxo-1H-benzimidazole-1-carboxamide hydrochloride) was
      a full agonist relative to 5-HT whilst BIMU 1 (endo-N-(8-methyl-8
      azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo - 1H-benzimidazole-1
      carboxamide hydrochloride) was a partial agonist with low intrinsic activity
      compared to 5-HT but had similar potency. We estimated a pKB of 7.9 for BIMU 1
      antagonism of 5-HT-induced tachycardia. DAU 6215 (N-endo-8-methyl-8
      azabicyclo[3.2.1]-oct-3-yl)-2,3-dihydro-2-oxo-lH-benzimidazole-l-carboxamide,
      hydrochloride) had no chronotropic activity and was found to be a simple
      competitive antagonist with a pKB of 7.15.SB 203186 (1-piperidinyl)ethyl lH
      indole 3-carboxylate) was a potent antagonist with a pKB of 8.3.The affinity of
      SB 203186 was approximately 20 times higher than that of tropisetron (ICS 205
      930;pKB= 6.9) and DAU 6215 (pKB= 7.0). GR1 13808 (([1-[2-[methylsulphonyl
      amino]ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3-carboxylate) and SDZ 205
      557 ((2-diethylaminoethyl)2-methoxy-4-amino-5-chloro-benzoate) also antagonized 5
      HT-induced tachycardia but not by simple competitive blockade.6. The sinoatrial 5
      HT4 receptor in the piglet has a pharmacological profile that correlates well
      with 5-HT4 receptors characterized in rat oesophagus, guinea-pig ileum and colon,
      mouse embryonic colliculi neurones and human atrium.

PMID- 8298791
TI  - Cardiovascular effects of SCA40, a novel potassium channel opener, in rats.
AB  - 1. Experiments have been performed to investigate the cardiovascular actions in
      the rat of SCA40, a novel potassium channel opener which is a potent relaxant of
      guinea-pig airway smooth muscle in vivo and in vitro. 2. SCA40 (0.01-30 microM)
      caused a complete and concentration-dependent relaxation of rat isolated thoracic
      aorta contracted with 20 mM KCl but failed to inhibit completely the spasmogenic
      effects of 80 mM KCl. 3. The ATP-sensitive K(+)-channel blocker, glibenclamide (3
      microM), failed to antagonize the relaxant action of SCA40 on 20 mM KCl
      contracted rat isolated thoracic aorta. 4. SCA40 (0.001-100 microM) had dual
      effects on rat isolated atria. At low concentrations, SCA40 produced a
      concentration-dependent decrease in the rate and force of contractions. At higher
      concentrations (greater than 1 microM) SCA40 induced concentration-dependent
      increases of atrial rate and force. 5. In vivo, in normotensive Wistar rats,
      SCA40 elicited a dose-dependent (1-100 micrograms kg-1) decrease in mean arterial
      pressure which was accompanied by a moderate dose-dependent increase in heart
      rate. SCA40 (100 micrograms kg-1) had a slightly greater hypotensive effect than
      cromakalim (100 micrograms kg-1) but the duration of the hypotension was longer
      with cromakalim than with SCA40. 6. The hypotensive effect of SCA40 was not
      reduced by propranolol, atropine, NG-nitro-L-arginine methyl ester (L-NAME) or
      glibenclamide. 7. It is concluded that the mechanism by with SCA40 relaxes
      vascular smooth muscle in vitro and in vivo involves activation of K(+)-channels
      distinct from glibenclamide-sensitive ATP-sensitive K(+)-channels.

PMID- 8298792
TI  - Levcromakalim may induce a voltage-independent K-current in rat portal veins by
      modifying the gating properties of the delayed rectifier.
AB  - 1. Smooth muscle cells of the rat portal vein were dispersed by enzymatic
      treatment and recordings of whole-cell currents under calcium-free conditions
      were made by the voltage-clamp technique. The effects of the potassium (K)
      channel opener, levcromakalim, on K-currents were compared with those of agents
      which modify protein phosphorylation. 2. Levcromakalim (1-10 microM) added to the
      extracellular (bath) fluid caused the development of a non-inactivating current
      (IK(ATP)) and simultaneously inhibited the delayed rectifier current (IK(V)) in a
      concentration-dependent manner. On prolonged exposure to levcromakalim (10
      microM), IK(ATP) declined and IK(V) was further diminished. 3. Addition to the
      pipette (intracellular) solution of the selective inhibitor of protein kinase C,
      calphostin C, itself had no effect on K-currents and did not modify the induction
      of IK(ATP) or the simultaneous inhibition of IK(V) produced by 1 microM
      levcromakalim. 4. Addition of the protein kinase inhibitor (PKI(6-22)amide, 1
      microM) to the pipette solution caused the production of a glibenclamide
      sensitive, non-inactivating current and inhibited IK(V). 5. In an assay system,
      levcromakalim (10 microM) did not inhibit the activity of purified protein kinase
      A (Type 1 or Type 2). 6. Addition to the pipette solution of the phosphatase
      inhibitor, okadaic acid (1 microM), did not itself modify K-currents and had
      little effect on the simultaneous induction of IK(ATP) and inhibition of IK(V) by
      levcromakalim (1 microM). 7. When the pipette solution contained 1 mM MgATP (but
      was depleted of substrates for ATP production), a non-inactivating, glibenclamide
      sensitive K-current developed spontaneously in 5 out of 11 cells with the
      simultaneous reduction of IK(V). In 3 of the 6 remaining cells, addition of the
      dephosphorylating agent, butanedione monoxime (5 mM) to the bath inhibited IK(V)
      and stimulated a glibenclamide-sensitive non-inactivating current. 8. Depletion
      of intracellular Mg2+ slightly enhanced IK(V). Under these conditions,
      levcromakalim (1 microM and 10 microM) did not significantly induce IK(ATP) or
      inhibit IK(V). 9. It is concluded that the effects of levcromakalim on K-currents
      can be mimicked by procedures designed to reduce channel phosphorylation. The
      results are consistent with the view that levcromkalim dephosphorylates the
      delayed rectifier channel, KV, which becomes converted into a voltage
      independent, non-inactivating form known as KATP. The possible mechanisms which
      underlie this interconversion are discussed.

PMID- 8298793
TI  - Characterization of purinoceptors mediating depolarization of rat isolated vagus
      nerve.
AB  - 1. As part of a broader study to characterize neuronal purinoceptors, the effects
      of adenosine 5'-triphosphate (ATP) and a range of ATP analogues were investigated
      on the extracellularly recorded membrane potential of the rat isolated vagus
      nerve, using a 'grease-gap' technique. 2. ATP evoked depolarization of the rat
      vagus nerve. The concentration-effect curve to ATP was not monophasic: at the
      lower concentrations (1 x 10(-5)-1 x 10(-3) M) the curve was shallow (< 50% of
      the near maximal response to 5-hydroxytryptamine (5-HT)) whilst at higher
      concentrations the relationship between concentration and amplitude of
      depolarization was steeper (> 135% of the response to 5-HT at the highest
      concentration tested, 1 x 10(-2) M). On washout of the high drug concentrations
      large after-hyperpolarizations were often observed. 3. alpha,beta-methylene ATP
      (1 x 10(-6)-3 x 10(-4) M), beta,gamma-methylene ATP (1 x 10(-6)-1 x 10(-3) M),
      and 5'-adenylylimidodiphosphate (beta,gamma-imido ATP; 1 x 10(-6)-1 x 10(-3) M)
      were all more potent than ATP and produced large depolarizations of the rat vagus
      nerve at the highest concentrations tested (> 150% of the response to 5-HT). The
      overall rank order of potency was alpha,beta-methylene ATP > beta,gamma-methylene
      ATP = beta,gamma-imido ATP > ATP. 4. In contrast, 2-methylthio ATP (1 x 10(-6)-1
      x 10(-3) M) produced relatively small depolarizations (< 100% of the response to
      5-HT). As was the case with low concentrations of ATP, the concentration-effect
      curve to 2-methylthio ATP was very shallow. 5. Adenosine 5'-diphosphate (ADP),
      adenosine 5'-monophosphate (AMP), adenosine and adenosine 5'-O-(2
      thiodiphosphate) (ADP-beta-s; all 1 x 10-6 1 x 10-3M) evoked only small
      depolarizations of the vagus nerve, amounting to 47 +/- 2.5%, 40.8 +/- 7.8%, 33.7
      +/- 3.3% and 62.4 +/- 12.7% of the response to 5-HT, respectively. Uridine 5'
      triphosphate (UTP; 1 X 10-6 1 X 10-3M) was inactive.6. The P2 purinoceptor
      antagonist, suramin (1 x 10-5-M-1 X 10-4 M), antagonized responses to alpha-beta
      methylene ATP. The nature of this antagonism was not, however, consistent with
      simple competitive kinetics between agonist and antagonist. Depolarizations
      produced by beta,gamma-methylene ATP and beta,gamma-imido ATP were also
      attenuated by suramin (1 x 10-4 M), but in contrast, suramin had no effect on
      responses to ADP, 2-methylthio ATP, ADP-beta-S or 5-HT.7. In addition to its
      antagonist effects, suramin (10-4 M) markedly increased the maximum amplitude of
      the depolarization produced by ATP.8. It is concluded that a heterogeneous
      receptor population mediates depolarization of the rat vagus nerve by purine
      nucleotides. Importantly, the large amplitude depolarizations to alpha,beta
      methylene ATP,beta,gamma-methylene ATP and beta,gamma-imido ATP are mediated via
      receptors that share many characteristics of the classical P2, receptor. In
      contrast, the relatively small depolarizing effects of ADP, ADP-beta-S and 2
      methylthio ATP were suramin-resistant. Although it appears that other
      purinoceptors are present,these data suggest that the rat vagus nerve may serve
      as a useful preparation for studying the pharmacology of neuronal P2x receptors.

PMID- 8298794
TI  - The effects of cholinoceptor agonists and antagonists on C-fibre evoked responses
      in the substantia gelatinosa of neonatal rat spinal cord slices.
AB  - 1. The effects of cholinoceptor agonists and antagonists were studied on neurones
      in the substantia gelatinosa (SG) of an in vitro spinal cord slice and nerve
      preparation from neonatal rats. 2. Bath application of carbachol (1-50 microM)
      reduced, in a dose-related manner, the amplitude and duration of the excitatory
      postsynaptic potentials (e.p.s.ps) evoked in response to nerve stimulation. 3.
      The latencies and stimulation thresholds required to evoke these e.p.s.ps
      suggested that the majority were due to C-fibre activation. 4. The reduction in
      e.p.s.p. amplitude and duration produced by carbachol was reversed by the
      muscarinic antagonists, atropine (in 8 out of 11 cells), pirenzepine (in 7 out of
      9 cells) and methoctramine (in 8 out of 9 cells) and by the nicotinic antagonist
      mecamylamine (in 3 out of 7 cells). 5. Injection of small hyperpolarizing or
      depolarizing pulses was associated with no change in conductance in 19 out of 26
      (73%) of cells tested, suggesting that an action at a site presynaptic to the
      neurone studied could account for part of the effect of carbachol. 6. It is
      proposed that some of the cholinoceptors associated with the e.p.s.p. depression
      are located on C-fibres.

PMID- 8298795
TI  - Attenuation of reperfusion hyperalgesia in the rat by systemic administration of
      benzodiazepines.
AB  - 1. An investigation into whether reperfusion hyperalgesia is modulated by prior
      systemic administration of two benzodiazepine agonists (diazepam and
      chlordiazepoxide), and an antagonist (flumazenil) was conducted. 2. Transient
      ischaemia was induced in conscious rats by applying an inflatable tourniquet to
      the base of the tail; when the rats exhibited a co-ordinated escape response, the
      tourniquet was deflated and reperfusion of the tail was allowed. Reperfusion
      hyperalgesia manifested as a decrease in tail flick latency, following tail
      immersion in 49 degrees C water, after the release of the tourniquet. 3.
      Intraperitoneal administration of diazepam, chlordiazepoxide and flumazenil had
      no effect on the co-ordinated escape to the noxious ischaemic stimulus nor on
      tail flick latency after application of a sham tourniquet. 4. The hyperalgesia
      evident during reperfusion, was abolished by diazepam (1 and 5 mg kg-1) and
      chlordiazepoxide (5 and 25 mg kg-1). The antihyperalgesic effects of both
      diazepam (5 mg kg-1) and chlordiazepoxide (25 mg kg-1) were inhibited by
      flumazenil (1 mg kg-1). 5. Rotarod performance was impaired in rats given
      diazepam and chlordiazepoxide at the same doses at which the benzodiazepines were
      antihyperalgesic. The impairment to motor function did not extend to the motor
      systems involved in the tail flick response. 6. In conclusion, benzodiazepines
      have antinociceptive properties during hyperalgesia.

PMID- 8298796
TI  - Adenosine receptor-induced second messenger production in adult guinea-pig
      cerebellum.
AB  - 1. The effects of adenosine receptor agonists on cyclic nucleotides accumulation
      were investigated in adult guinea-pig cerebellar slices by use of radioactive
      precursors. 2. Adenosine elicited a rapid and maintained increase in cyclic AMP,
      that was fully reversed upon addition of adenosine deaminase. Adenosine analogues
      stimulated cyclic AMP generation up to 40 fold with the rank order of potency: 5'
      N-ethylcarboxamidoadenosine (0.6 microM) > 2-chloroadenosine (6 microM) >
      adenosine (13 microM). CGS 21680 (10 microM) elicited only a small stimulation
      (1.2 fold). 3. The cyclic AMP response to NECA was reversed by the 1,3
      dipropylxanthine-based adenosine receptor antagonists 8-[4-[[[[(2
      aminoethyl)amino]amino]carbonyl]methyl]oxy]- phenyl]-1,3-dipropylxanthine (XAC),
      8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and N-[2-(dimethylamino)ethyl]N-methyl
      4-(1,3-dipropylxanthine)benzene sulphonamide (PD 115,199) with estimated apparent
      inhibition constants of 15, 81 and 117 nM, respectively. 4. Pretreatment with
      adenosine also potentiated the cyclic GMP response to sodium nitroprusside,
      abolishing the decline in [3H]-cyclic GMP observed with sodium nitroprusside
      alone, and allowing [3H]-cyclic GMP levels to be maintained for at least an
      additional 10 min. This potentiation was fully reversed by adenosine deaminase.
      5. Adenosine analogues potentiated the sodium nitroprusside-elicited cyclic GMP
      generation with the rank order of potency: 5'-N-ethylcarboxamidoadenosine (0.7
      microM) > 2-chloroadenosine (6 microM) > adenosine (42 microM). 6. NECA
      potentiation of cyclic GMP formation was reversed by the antagonists XAC, DPCPX
      and PD 115,199 with apparent inhibition constants of 17, 102 and 242 nM,
      respectively. 7. The similar potencies of adenosine analogues and xanthine
      antagonists for stimulation of cyclic AMP and potentiation of cyclic GMP lead to
      the suggestion that these phenomena are mediated through the same adenosine
      receptor, the A2b receptor. Furthermore, we suggest that potentiation of the
      sodium nitroprusside-induced cyclic GMP response may be mediated at the level of
      phosphodiesterase hydrolysis of the cyclic nucleotides.

PMID- 8298797
TI  - Effects of pyrimidines on the guinea-pig coronary vasculature.
AB  - 1. The effects of the pyrimidines, uridine 5'-triphosphate (UTP), thymidine 5'
      triphosphate (TTP) and cytidine 5'-triphosphate (CTP), were examined in the
      guinea-pig coronary bed, by use of a Langendorff technique. Comparisons were made
      with the actions of the purines adenosine 5'-triphosphate (ATP), inosine 5'
      triphosphate (ITP) and guanosine 5'-triphosphate (GTP). The effect of, the nitric
      oxide synthase inhibitor, L-NG-nitroarginine methyl ester (L-NAME) and, the
      prostaglandin synthesis inhibitor, indomethacin on the vasodilator response to
      these purines and pyrimidines was examined. The effects of these inhibitors were
      assessed on their ability to inhibit both the amplitude and the area of the
      vasodilator response. 2. The relative order of potency of the purines and
      pyrimidines studied was ATP > UTP > ITP >> GTP, TTP, CTP. 3. The maximum
      amplitude and area of the vasodilator response to the pyrimidines, UTP (5 x 10(
      10)-5 x 10(-7) mol), TTP (5 x 10(-8)-5 x 10(-7) mol) and CTP (5 x 10(-7) mol),
      and purines, ITP (5 x 10(-9)-5 x 10(-7) mol) and GTP (5 x 10(-8)-5 x 10(-7) mol),
      were significantly reduced by L-NAME (3 x 10(-5) and 10(-4) M). 4. The inhibition
      of the response to ATP (5 x 10-8 mol), UTP (5 x 10-8 mol), ITP (5 x 10-8 mol),
      TTP(5 x 10-7 mol), CTP (5 x 10- mol) and GTP (5 x 10- mol) by L-NAME (3 x 10-5 M)
      was significantly reversed by L-arginine (1.5 x 10-3 M).5. L-NAME (3 x 10-5 and
      10-4 M) only inhibited the amplitude of the vasodilator response to a low dose of
      ATP (5 x 10-mol), although the area of vasodilator response to ATP(5 x 10-11-5 x
      10-7 mol) was significantly reduced by L-NAME (3 x 10-5 and 10-4 M).6. The
      maximum amplitude of the vasodilator response to ATP (5 x 10-10-5 x 10-7 mol) was
      significantly reduced by indomethacin (10-6 M), although the area of the
      vasodilator response to ATP was only significantly reduced at one intermediate
      dose (5 x 10-9 mol). Indomethacin (10-6 M) did not affect the maximum amplitude
      or area of the vasodilator responses to UTP (5 x 10-11-5 x 10-7 mol),ITP (5 x 10
      10-5 x 10-7 mol), CTP (5 x 10-7 mol), TTP (5 x 10-8-5 x 10-7 mol) and GTP(5 x 10
      8-5 x 10-7 mol).7. It is concluded that in the guinea-pig coronary vasculature,
      the vasodilatation evoked by the pyrimidines, UTP, TTP and CTP, was mediated in
      large part via nitric oxide, as were the vasodilatations evoked by the purines
      ITP and GTP. The vasodilatations evoked by ATP, however, appear to involve
      prostanoids in addition to the release of nitric oxide.

PMID- 8298798
TI  - Vasoconstrictor effects of various neuropeptide Y analogues on the rat tail
      artery in the presence of phenylephrine.
AB  - 1. The increase in perfusion pressure induced by neuropeptide Y (NPY), peptide YY
      (PYY) and related peptides were compared in the perfused rat tail artery
      precontracted by a submaximal concentration (1 microM) of the vasoconstrictor,
      phenylephrine. 2. NPY, PYY, [Leu31,Pro34]NPY, [Glu16,Ser18,Ala22,Leu28,31]NPY
      (ESALL-NPY) and the centrally truncated and stabilized analogues [D-Cys5,8
      aminooctanoic acid7-20, Cys24]-NPY (D-Cys5-NPY) and [D-Cys7, 8-aminooctanoic
      acid8-17,Cys20]-NPY (D-Cys7-NPY) produced a concentration-dependent enhancement
      of the vasoconstrictor response induced by 1 microM phenylephrine. PYY was two
      times more potent than NPY and [Leu31,Pro34]NPY while ESALL-NPY, D-Cys7-NPY and D
      Cys5-NPY were approximately 3, 5 and 16 times less potent than NPY respectively.
      NPY, D-Cys5-NPY and D-Cys7-NPY gave similar maximal responses whereas those
      observed for PYY, [Leu31,Pro34]NPY and ESALL-NPY were much greater than that of
      NPY. 3. NPY 13-36 and [des-Ser3,Lys4,Cys2,8-aminooctanoic acid3-24, D-Cys27]-NPY
      ([es-Ser3,Lys4]Cys2-NPY) were practically inactive at concentrations up to 3
      microM, whereas [des-Ser3,Lys4,D-Cys2,8-aminooctanoic acid3-24,Cys27]-NPY ([des
      Ser3,Lys4]D-Cys2-NPY), which differs from [des-Ser3,Lys4]Cys2-NPY in the
      disulphide bridge (a D-Cys in position 2 for [des-Ser3,Lys4]D-Cys2-NPY instead of
      an L-CYs for [des-Ser3,Lys4]Cys2-NPY) was a weak agonist the maximal effect of
      which could not be ascertained. 4. The contractile effects of [des-Ser3,Lys4]D
      Cys2-NPY were additive with those of NPY and [Leu31,Pro34]NPY demonstrating that
      it is not a partial agonist but may simply not interact competitively with the
      receptor binding site for NPY. NPY and PYY interacted in a manner expected of
      agonists competing for the same binding site.5. PYY, NPY and [Leu31,Pro34]NPY
      were equipotent in displacing the I125-labelled PYY from binding sites on
      membranes from Y1-receptor expressing SK-N-MC cells, while the centrally
      truncated analogues were much less potent. The rank order of potencies for
      displacement of the I125-PYY binding by these peptides in SK-N-MC cells
      correlated with their activity in enhancing the vasoconstrictor response of
      phenylephrine in the tail artery. For the [des-Ser3,Lys4]D-Cys2-NPY analogue, the
      displacement pattern was more complex in that the displacement analysis revealed
      the presence of two binding sites.6. In conclusion, these data provide no
      evidence for other than postjunctional Y1-receptors mediating the enhancement of
      the contractile response elicited by phenylephrine in the perfused rat tail
      artery. The effects of [des-Ser3,Lys4]D-Cys2-NPY indicate that the Y1-receptor
      may possess an allosteric binding site.

PMID- 8298799
TI  - Impaired sensory-motor nerve function in the isolated mesenteric arterial bed of
      streptozotocin-diabetic and ganglioside-treated streptozotocin-diabetic rats.
AB  - 1. Adult male Wistar rats were treated with streptozotocin (65 mg kg-1, i.p.) to
      induce diabetes. Subgroups of age-matched control and streptozotocin-treated rats
      were given daily injections of mixed brain bovine gangliosides (60 mg kg-1 body
      weight, i.p.). At eight weeks after treatment mesenteric arterial beds from rats
      in each of the four groups were isolated and perfused and the function of
      perivascular nerves (sympathetic and sensory-motor), endothelium and smooth
      muscle was assessed. 2. Values for basal tone of mesenteric beds from diabetic
      and diabetic-ganglioside rats were significantly lower than those of the control
      and control-ganglioside-treated rats. Perfusion pressures at basal tone were
      25.55 +/- 0.8 (n = 11), 22.58 +/- 1.5 (n = 12), 28.42 +/- 1.6 (n = 12) and 30.67
      +/- 1.9 (n = 12) mmHg for diabetic, diabetic-ganglioside, control and control
      ganglioside-treated rats respectively. 3. There was no difference between the
      groups with respect to vasoconstrictor responses to sympathetic nerve
      stimulation, or to doses of noradrenaline. Vasoconstrictor responses to potassium
      chloride were also similar between the groups. 4. Perivascular nerve stimulation
      in the presence of the sympathetic blocker guanethidine (3 microM), with tone of
      the preparation raised with methoxamine (3-100 microM), elicited frequency
      dependent vasodilatation of mesenteric arterial beds due to transmitter release
      from sensory-motor nerves. Sensory-motor nerve-induced vasodilator responses of
      mesenteric arterial beds from streptozotocin-diabetic and ganglioside-treated
      diabetic rats were significantly smaller than those of mesenteric beds from the
      controls (untreated and ganglioside-treated). Vasodilator responses to
      exogenously applied calcitonin gene-related peptide, the principal vasodilator
      transmitter released from these nerves, were not different between the groups.
      Vasodilator responses to the sensory neurotoxin capsaicin were also not different
      between the groups.5. Endothelium-dependent vasodilator responses to
      acetylcholine were similar between the groups as were those to the endothelium
      independent vasodilator sodium nitroprusside.6. These results indicate that
      streptozotocin-induced diabetes produces marked impairment of sensory motor nerve
      function in the rat mesenteric arterial bed. The significantly lower basal
      perfusion pressures of mesenteric beds from diabetic rats compared to controls
      may be a reflection of sympathetic dysfunction, but no differences were apparent
      from the vasoconstrictor responses produced when sympathetic nerves were
      electrically stimulated. There was no evidence for changes in endothelial
      vasodilator function, or smooth muscle vasodilator and vasoconstrictor function.
      Ganglioside treatment did not modify any aspect of vascular function of
      mesenteric beds from streptozotocin-diabetic or control rats.

PMID- 8298800
TI  - Effects of a water-soluble forskolin derivative (NKH477) and a membrane-permeable
      cyclic AMP analogue on noradrenaline-induced Ca2+ mobilization in smooth muscle
      of rabbit mesenteric artery.
AB  - 1. Effects were studied of 6-(3-dimethylaminopropionyl) forskolin (NKH477), a
      water-soluble forskolin derivative and of dibutyryl-cyclic AMP, a membrane
      permeable cyclic AMP analogue on noradrenaline (NA)-induced Ca2+ mobilization in
      smooth muscle strips of the rabbit mesenteric artery. The intracellular
      concentration of Ca2+ ([Ca2+]i), isometric force and cellular concentration of
      inositol 1,4,5-trisphosphate (InsP3) were measured. 2. NA (10 microM) produced a
      phasic, followed by a tonic increase in both [Ca2+]i and force in a solution
      containing 2.6 mM Ca2+. NKH477 (0.01-0.3 microM) attenuated the phasic and the
      tonic increases in both [Ca2+]i and force induced by 10 microM NA, in a
      concentration-dependent manner. 3. In Ca(2+)-free solution containing 2 mM EGTA
      with 5.9 mM K+, NA (10 microM) produced only phasic increases in [Ca2+]i and
      force. NKH477 (0.01 microM) and dibutyryl-cyclic AMP (0.1 mM) each greatly
      inhibited these increases. 4. NA (10 microM) led to the production of InsP3 in
      intact smooth muscle strips and InsP3 (10 microM) increased Ca2+ in Ca(2+)-free
      solution after a brief application of Ca2+ in beta-escin-skinned smooth muscle
      strips. NKH477 (0.01 microM) or dibutyryl-cyclic AMP (0.1 mM) modified neither
      the NA-induced synthesis of InsP3 in intact muscle strips nor the InsP3-induced
      Ca2+ release in skinned strips. 5. In Ca(2+)-free solution, high K+ (40 and 128
      mM) itself failed to increase [Ca2+]i but concentration-dependently enhanced the
      amplitude of the increase in [Ca2+]i induced by 10 microM NA with a parallel
      enhancement of the maximum rate of rise. The extent of the inhibition induced by
      NKH477 (0.01 microM)or dibutyryl-cyclic AMP (0.1 mM) on the NA-induced [Ca2+]
      increase was inversely related to the maximum rate of rise of [Ca2+], induced by
      NA in Ca2+-free solution containing various concentrations of K+. These results
      suggest that the increase in the rate of Ca2+ release induced by NA can conceal
      the inhibitory action on NA-induced Ca2+ mobilization of agents that increase
      cyclic AMP.6. Repetitive application of 10 JAM NA in Ca2+-free solution led to a
      disappearance of the NA-induced increase in [Ca2+]j, but NA could again increase
      [Ca2+], in Ca2+-free solution after a brief application of Ca2+ with 40 mM K+
      ('Ca2+-loading'). The magnitude of this NA-induced increase in [Ca2+]i depended
      on the duration of the Ca2+-loading. With application of dibutyryl-cyclic AMP
      (0.1 mM) during the Ca2+-loading period, the loading duration required for the
      restoration of the maximum NA-response was shortened.7. Cyclopiazonic acid (10
      microM, an inhibitor of Ca2+-ATPase at intracellular storage sites) attenuated
      the inhibitory action of dibutyryl-cyclic AMP on the NA-induced increase in
      [Ca2+], in Ca2+-free solution.When NA (10 microM) was applied twice for 30 s with
      a 10 min interval in Ca2+-free solution, the amplitude of response to the second
      application was about one third of the first response. With application of 0.1 mM
      dibutyryl-cyclic AMP during the first application of NA, the increase in [Ca2+],
      induced by the first application of NA was inhibited, but the response induced by
      the second was enhanced. These results suggest that dibutyryl-cyclic AMP enhances
      Ca2+ uptake into the NA-sensitive storage sites.8. We conclude that, in smooth
      muscle of the rabbit mesenteric artery, agents that increase cyclic AMP inhibit
      the NA-induced increase in [Ca2+] through an activation of Ca2+ uptake into the
      cellular storage sites.

PMID- 8298801
TI  - Block of potassium currents in rat isolated sympathetic neurones by tricyclic
      antidepressants and structurally related compounds.
AB  - 1. The block of K+ currents by the tricyclic antidepressants (TCAs), imipramine
      and amitriptyline and three structurally related compounds, chlorpromazine,
      tacrine and carbamazepine was investigated in rat isolated sympathetic neurones
      by whole-cell voltage-clamp recording. 2. At a concentration of 10 microM,
      imipramine, amitriptyline and chlorpromazine all blocked the delayed rectifier K+
      current (IKv) by about the same extent, 54%, 47% and 53%. Tacrine was less
      effective (10%) while carbamazepine was ineffective at all concentrations tested.
      3. The degree of block by the four effective compounds was relatively independent
      of the size of the voltage-step. Neither the activation nor the inactivation
      rates of IKv were altered by the blocking drugs. 4. Concentration-response
      relationships for imipramine and tacrine showed that imipramine was about 7 fold
      more potent than tacrine but that the maximum inhibition and the Hill slope were
      the same for both compounds. 5. Amitriptyline, chlorpromazine and imipramine (at
      10 microM) were 2-3 fold more potent at inhibiting the sustained K+ current
      (mostly IKv) than the transient K+ current (mostly IA). Tacrine, however, was
      equally effective in blocking both components.

PMID- 8298802
TI  - The effects of beta-adrenoceptor activation on contraction in isolated fast- and
      slow-twitch skeletal muscle fibres of the rat.
AB  - 1. The aim of the experiments was to examined the effects of beta-adrenoceptor
      activation on twitch and tetanic contractions in fast- and slow-twitch mammalian
      skeletal muscle fibres. Isometric force was recorded from bundles of intact
      fibres isolated from the normal and denervated slow-twitch soleus and normal fast
      twitch sternomastoid muscles of the rat. 2. Terbutaline (10 microM), a beta 2
      adrenoceptor agonist, induced an average 15% potentiation of peak twitch and peak
      tetanic force in normal soleus fibres and abbreviated twitch and tetanic
      relaxation. In white- and red-sternomastoid fibres, 10 microM terbutaline
      potentiated peak twitch force by about 7% and slowed twitch relaxation. 3. The
      potentiation of twitches and tetani by terbutaline was quantitatively similar in
      normal and denervated soleus fibres. However, in contrast to the normal soleus,
      terbutaline slowed twitch relaxation and had no effect on tetanic relaxation in
      denervated soleus fibres. 4. Adrenaline (10 microM) increased peak tetanic force
      by about 7% in both normal and denervated soleus fibres. 5. Exposure to (+/-)
      propranolol (0.1 microM), a general beta-adrenoceptor blocker, completely
      abolished the tetanus potentiation by terbutaline. 6. Dibutyryl-cyclic AMP (2 mM)
      mimicked the effects of 10 microM terbutaline on peak tetanic force and tetanic
      relaxation in normal and denervated soleus fibres. Dibutyryl-cyclic AMP also
      potentiated peak twitch force in denervated soleus fibres but only after a brief
      period of twitch depression: the twitch depression might be due to butyrate. 7.
      The results suggest that the increase in peak twitch and tetanic force and
      abbreviation of tetanic relaxation induced by terbutaline depend on the
      activation of beta-adrenoceptors and a consequent increase in the myoplasmic
      cyclic AMP concentration.

PMID- 8298803
TI  - R56865 inhibits catecholamine release from bovine chromaffin cells by blocking
      calcium channels.
AB  - 1. The effects of R56865 (a new class of cardioprotective agent which prevents
      Na+ and Ca2+ overload in cardiac myocytes) on catecholamine release, whole-cell
      current through Ca2+ channels (IBa) and cytosolic Ca2+ concentrations, [Ca2+]i,
      have been studied in bovine chromaffin cells. 2. R56865 caused a time- and
      concentration-dependent blockade of catecholamine release from superfused cells
      stimulated intermittently with 5 s pulses of 59 mM K+. After 5 min superfusion, a
      3 microM concentration inhibited secretion by 20%; the blockade increased
      gradually with perfusion time, to reach 85% after 40 min. The IC50 to block
      secretion after 5 min periods of exposure to increasing concentrations of R56865
      was around 3.1 microM. The blocking effects of R56865 were reversible after 5-15
      min wash out. In high Ca2+ solution (10 mM Ca2+), the degree of blockade of
      secretion diminished by 20% in comparison with 1 mM Ca2+. 3. In electroporated
      cells, R56865 (10 microM) did not modify the secretory response induced by the
      application of 10 microM free Ca2+. 4. R56865 blocked the peak IBa current in a
      concentration- and time-dependent manner; its IC50 was very similar to that
      obtained for secretion (3 microM). The compound not only reduced the size of the
      peak current but also promoted its inactivation; when the effects of R56865 were
      measured at the most inactivated part of the current, its IC50 was 1 microM. Both
      the inactivation and the reduction of the peak currents were reversible upon
      washing out the drug. 5. In fura-2-loaded single chromaffin cells the basal
      [Ca2+]i of around 100 nM was elevated to a peak of1.5 microM by the application
      of a 5 s pulse of 59 mM K+. R56865 (10 microM) did not affect the basal [Ca2+]but
      blocked by 90% the K+-evoked increase. This effect was fully reversible after 5
      10 min of wash out.6. The results are compatible with the idea that R56865 blocks
      Ca2+ entry into K+-depolarized chromaffin cells by promoting the inactivation of
      voltage-dependent Ca2+ channels; this would lead to the limitation of the rise in
      [Ca2+]i and of the release of catecholamines. The restriction of catecholamine
      release may favour indirectly the known direct beneficial cardioprotective
      actions of R56865.

PMID- 8298804
TI  - Effects of the novel potassium channel opener, UR-8225, on contractile responses
      in rat isolated smooth muscle.
AB  - 1. The effects of UR-8225 [(1,2-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2
      dimethyl-1-oxonapht halen-6- carbonitrile)] and levcromakalim were studied on the
      electrical and contractile responses induced by noradrenaline and KCl and on
      86Rb+ efflux in rat aortic rings and on spontaneous mechanical activity in rat
      portal vein segments. 2. UR-8225 and levcromakalim, 10(-9) M-10(-5) M, relaxed
      the contractile responses induced by noradrenaline (IC50 = 2.7 +/- 0.4 x 10(-6) M
      and 6.6 +/- 1.3 x 10(-7) M, respectively) or 30 mM KCl (IC50 = 1.4 +/- 0.2 x 10(
      7) M and 9.4 +/- 1.3 x 10(-8) M, respectively) more effectively than those
      induced by 80 mM KCl. The relaxant effect on noradrenaline-induced contractions
      was independent of the presence or absence of functional endothelium. 3. The
      vasorelaxant effect of UR-8225 and levcromakalim can be competitively antagonized
      by glibenclamide, an ATP-sensitive K+ channel blocker. There were no differences
      in the calculated pA2 values for glibenclamide to inhibit UR-8225- and
      levcromakalim-induced relaxations (7.61 +/- 0.08 and 7.69 +/- 0.10,
      respectively). The slope of the Schild plot yielded values not significantly
      different from unity (0.95 +/- 0.06 and 0.96 +/- 0.05, respectively). 4. UR-8225
      (10(-5) M) hyperpolarized the resting aortic membrane potential from -50.7 +/-
      0.7 mV to -66.0 +/- 2.0 mV and stimulated 86Rb+ efflux. 5. UR-8225 and
      levcromakalim inhibited the contractions induced by Ca2+ in aortae incubated in
      Ca(2+)-free PSS containing methoxyverapamil in the presence of noradrenaline. 6.
      Both drugs inhibited the amplitude of spontaneous activity in portal veins (IC50
      = 5.1 +/- 1.4 x 10-8 M and 1.5 +/- 0.7 x 10-8 M, respectively), this effect being
      competitively antagonized by glibenclamide.7. These results indicated that UR
      8225 exhibited qualitatively similar, but slightly less potent,vasorelaxant
      effects than those exerted by levcromakalim, which suggests that they can be
      related to its ability to activate ATP-sensitive K+ channels in vascular smooth
      muscle cells.

PMID- 8298805
TI  - Blockade of human atrial 5-HT4 receptors by GR 113808.
AB  - 1. The mode of antagonism of 5-hydroxytryptamine (5-HT)-induced positive
      inotropic effects by the highly selective 5-HT4 receptor antagonist GR 113808 ([1
      [2-methylsulphonylamino ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3
      carboxylate) was investigated on isolated preparations of human right atrium. 2.
      GR 113808 caused concentration-dependent (2-100 nM) surmountable antagonism of
      the effects of 5-HT with a pKB (M) of 8.8. 3. The affinity of GR 113808 for human
      atrial 5-HT4 receptors, together with its high selectivity for 5-HT4 receptors
      comprise useful properties for investigating the question of 5-HT4 receptor
      subtypes.

PMID- 8298806
TI  - Endothelin receptor subtypes in human and guinea-pig pulmonary tissues.
AB  - 1. In this study the endothelin (ET) receptor subtypes mediating contractions
      produced by ET-1 in human and guinea-pig pulmonary tissues were investigated. In
      addition the receptor responsible for ET-1-induced prostanoid release in human
      bronchus was determined. 2. In human bronchus and human pulmonary artery ET-1
      (0.1 nM-0.3 microM) was a potent and effective contractile agent (pD2 = 7.58 +/-
      0.15, n = 6, and 8.48 +/- 0.11, n = 7, respectively). BQ-123 (1-10 microM), a
      potent and selective ETA receptor antagonist, potently antagonized ET-1-induced
      contraction in human pulmonary artery (pKB = 6.8 with 1 microM BQ-123, n = 7) but
      had no effect in human bronchus (n = 6). 3. Sarafotoxin S6c (0.1 nM-0.1 microM),
      the ETB-selective agonist, did not contract human pulmonary artery (n = 5), but
      potently and effectively contracted human bronchus: pD2 = 8.41 +/- 0.17, maximum
      response = 74.4 +/- 3.1% of 10 microM carbachol; n = 5. BQ-123 (1-10 microM) did
      not antagonize sarafotoxin S6c-induced contraction in human bronchus (n = 5). 4.
      ET-1 potently contracted guinea-pig trachea, bronchus, pulmonary artery and aorta
      (pD2 = 8.15 +/- 0.14, 7.72 +/- 0.12, 8.52 +/- 0.12, and 8.18 +/- 0.12,
      respectively, n = 6-14). BQ-123 (0.1-10 microM)antagonized ET-1-induced
      contractions in guinea-pig pulmonary artery (pKB = 6.7 with 1 microM BQ-123,n =
      6), aorta (pKB = 7.1 with 1 microM BQ-123, n = 6) and trachea (pKB = 6.2 with 1
      microM BQ-123, n = 6) butwas without marked effect in bronchus (n = 4). In
      contrast, sarafotoxin S6c (0.1 nM-0.l microM) did not contract guinea-pig aorta
      (n = 4) or guinea-pig pulmonary artery (n = 6) but potently and effectively
      contracted guinea-pig bronchus: pD2= 8.55 +/- 0. 1; maximum contraction = 63.6
      +/0 3.1% of 10 microM carbachol,n = 4. Sarafotoxin S6c (0.1 nM-0. 1 microM) was a
      much less effective agonist in guinea-pig trachea:maximum contraction = 13.9 +/-
      2.5% of 10 JM carbachol, n = 4; P< 0.0001, compared to bronchus.Contractions
      produced by sarafotoxin S6c in guinea-pig bronchus or trachea were unaffected by
      BQ-123(IO microM, n=4).5. Significant differences were observed in the efficacy,
      relative to carbachol, but not the potency of sarafotoxin S6c in guinea-pig
      airways, with a much greater maximum contractile response in bronchus(69.6 +/-
      2.4% of 10 microM carbachol, n = 6) or lower region of the trachea (48.5 +/- 5.9%
      of 10 microM carbachol,n = 6) than in the middle region of the trachea (14.4 +/-
      4.0% of 10 microM carbachol, n = 6) or the upper region of the trachea (19.3 +/-
      2.7% of 10 microM carbachol, n = 6). There were minimal regional differences in
      either ET-1-induced contraction or the potency of BQ-123 (3 microM) for
      inhibition of responses to ET-1 in guinea-pig airways.6. Release of various
      prostanoids in human bronchus induced by ET-1 (0.3 microM) was essentially
      abolished with 10 IM BQ-123.7. These data provide evidence that distinct ET
      receptors mediate ET-1-induced contraction in human pulmonary artery, guinea-pig
      pulmonary artery and guinea-pig aorta (ETA subtype) compared with human bronchus
      and guinea-pig bronchus (non-ETA, perhaps ETB subtype). Contractions to ET-1 in
      guinea-pig trachea appear to involve both ETA and non-ETA (ETB?) receptor
      subtypes. Furthermore,regional differences appear to exist in the relative
      distribution of ET receptor subtypes in guinea-pig airways. In human bronchus ET
      1-induced prostanoid release, unlike the contractile response, appears to be
      mediated via ETA receptor activation.

PMID- 8298807
TI  - Nitric oxide-mediated changes in vascular reactivity in pregnancy in
      spontaneously hypertensive rats.
AB  - 1. To examine the mechanisms which may account for pregnancy-induced
      vasodilatation in spontaneously hypertensive rats (SHR), we have investigated the
      changes in vascular reactivity and the effects of endothelial nitric oxide (NO)
      inhibition in the in situ blood-perfused, mesenteric resistance vessels of 18-20
      day pregnant SHR. The effects of NG-nitro-L-arginine (L-NOARG) were compared in
      pregnant and nonpregnant SHR and gestation matched normotensive Wistar-Kyoto
      (WKY) rats. 2. Intra-arterial mean blood pressures (MBP) were similar in pregnant
      and nonpregnant SHR. Basal perfusion pressures (BPP) were decreased in pregnant
      compared with nonpregnant SHR. Pregnant WKY had lower MBP and BPP than either
      pregnant or nonpregnant SHR. 3. Vasoconstrictor responses to electrical
      stimulation (ES) and intra-arterial noradrenaline (NA) were decreased in pregnant
      compared with nonpregnant SHR. These responses were still greater in pregnant SHR
      when compared with pregnant WKY. Vascular reactivity to angiotensin II (AII) in
      pregnant SHR was reduced to a similar level to that in pregnant WKY. 4. L-NOARG
      (5 mg kg-1, i.v.), an inhibitor of nitric oxide synthase, increased MBP and BPP
      in all groups. After L-NOARG, BPP were equalized between pregnant and nonpregnant
      SHR. Pregnant WKY still showed lower MBP and BPP than SHR groups. 5. L-NOARG
      potentiated vascular responses to ES, NA and AII in all groups. The blunted
      vascular responses to NA and ES were normalized and the reactivity to AII was
      only partially reversed in pregnant SHR compared with nonpregnant SHR. Pregnant
      WKY still had much lower vascular responses to ES and NA than either pregnant or
      nonpregnant SHR. L-NOARG enhanced vascular responses to All to a greater extent
      in pregnant SHR than in pregnant WKY.6. These results demonstrate that blunted
      responses to NA and ES were NO-dependent, while diminished reactivity to AII was
      only partially dependent on NO in the in situ blood perfused mesenteric
      resistance vessels of pregnant SHR.7. The present results in pregnant SHR differ
      from our previous finding with pregnant normotensive WKY, in which blunted
      responses to NA, but not to ES, were equalized by L-NOARG. Pregnancy induced
      vasodilatation in hypertensive rats appears to be more dependent on endothelial
      NO than in normotensive WKY. A defect of the endothelial NO generating pathway
      which promotes vasodilatation in pregnancy may contribute to the predisposition
      of women with essential hypertension to develop pre-eclampsia.

PMID- 8298808
TI  - L-694,247: a potent 5-HT1D receptor agonist.
AB  - 1. The 5-hydroxytryptamine (5-HT) receptor binding selectivity profile of a
      novel, potent 5-HT1D receptor agonist, L-694,247 (2-[5-[3-(4
      methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl ]- 1H-indole-3-yl]ethylamine)
      was assessed and compared with that of the 5-HT1-like receptor agonist,
      sumatriptan. 2. L-694,247 had an affinity (pIC50) of 10.03 at the 5-HT1D binding
      site and 9.08 at the 5-HT1B binding site (sumatriptan: pIC50 values 8.22 and 5.94
      respectively). L-694,247 retained good selectivity with respect to the 5-HT1A
      binding site (pIC50 = 8.64), the 5-HT1C binding site (6.42), the 5-HT2 binding
      site (6.50) and the 5-HT1E binding site (5.66). The pIC50 values for sumatriptan
      at these radioligand binding sites were 6.14, 5.0, < 5.0 and 5.64 respectively.
      Both L-694,247 and sumatriptan were essentially inactive at the 5-HT3 recognition
      site. 3. L-694,247, like sumatriptan, displayed a similar efficacy to 5-HT in
      inhibiting forskolin-stimulated adenylyl cyclase in guinea-pig substantia nigra
      although L-694,247 (pEC50 = 9.1) was more potent than sumatriptan (6.2) in this 5
      HT1D receptor mediated functional response. L-694,247 (pEC50 = 9.4) was also more
      potent than sumatriptan (6.5) in a second 5-HT1D receptor mediated functional
      response, the inhibition of K(+)-evoked [3H]-5-HT release from guinea-pig frontal
      cortex slices. 4. The excellent agreement observed for L-694,247 between the 5
      HTlD radioligand binding affinity and the functional potency confirm that the two
      functional models (the inhibition of forskolin-stimulated adenylyl cyclase in
      guinea-pig substantia nigra and the inhibition of K+-evoked [3H]-5-HT release
      from guinea-pig frontal cortex) do indeed reflect 5-HTID-mediated events.5. L
      694,247 is a novel, highly potent 5-HTID/5-HTIB receptor ligand which should
      prove useful for the exploration of the physiological role of these receptors in
      animals.

PMID- 8298809
TI  - Evidence for heterogeneity of endothelin receptor distribution in human coronary
      artery.
AB  - 1. The receptors mediating endothelin-evoked contraction of human coronary artery
      have been investigated in isolated segments of the left anterior descending
      coronary artery (LAD). 2. Endothelin-1 (ET-1) was 10 times more potent in distal
      than in proximal segments but the potency ratio between ET-1 and ET-3 (endothelin
      3) was similar and close to 100 in any segment of the artery. 3. BQ-123, an ETA
      receptor antagonist, competitively antagonized the response to ET-1 of distal
      segments (pA2 equal to 7.47). In the proximal segments, part of the contractile
      response was BQ123 sensitive, but the antagonism was non-competitive. In both
      groups of segments, the response to ET-3 could be completely blocked by BQ-123.
      4. These observations indicate that ETA receptors mediate the contractile
      response to ET-1 in distal, pre-resistant coronary arteries, but that other ET
      receptors are also involved in the contractile response of proximal segments.

PMID- 8298810
TI  - Formation of sulphidopeptide-leukotrienes by cell-cell interaction causes
      coronary vasoconstriction in isolated, cell-perfused heart of rabbit.
AB  - 1. We have studied the transcellular biosynthesis of bioactive leukotrienes
      (LTs), generated upon blood cell-vascular wall interactions and their functional
      consequences, in the spontaneously beating, cell-perfused, heart of the rabbit.
      Rabbit isolated hearts were perfused under recirculating conditions (50 ml) with
      5 x 10(6) cells of unpurified (buffy coat) or purified human neutrophils (PMNL),
      and challenged with 0.5 microM A23187 for 30 min. Coronary perfusion pressure
      (CPP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP) and left
      ventricular pressure (LVP) were monitored continuously. Leukotriene formation was
      measured by specific enzyme-immunoassay and confirmed by reversed phase h.p.l.c.
      and u.v. spectral analysis. 2. Basal CPP values averaged 44 +/- 1.4 mmHg; A23187
      triggered a marked increase in CPP both in the presence of buffy coat cells
      (+100% above basal) and PMNL (+270% above basal); the latter change in CPP was
      accompanied by a rise in LVEDP (+138% above basal). 3. The increase in CPP was
      preceded by a statistically significant rise in iLTC4-D4 concentration in the
      circulating buffer. Pretreatment with two structurally unrelated LTD4 receptor
      antagonists, LY171883 and SKF104353 (10 microM), fully prevented the increase in
      CPP and LVEDP. A similar protection was also observed when the rabbit heart was
      perfused with PMNL that had been pretreated with MK886 (1 microM), a potent
      inhibitor of leukotriene biosynthesis. 4. The increased coronary tone was
      accompanied by a marked release of lactate dehydrogenase (LDH), a marker of
      ischaemic damage; pretreatment of the heart with the LTD4 receptor antagonists as
      well as of the PMNL with MK886 resulted in a complete suppression of LDH activity
      release. 5. Positive identification of LTC4-D4 in the perfusates was obtained and
      a significant correlation observed between the CPP values and iLTC4-D4
      concentrations.6. This study suggests that challenge of PMNL present within the
      coronary vasculature, causes a LTD4-dependent coronary vasoconstriction, favoured
      by an efficient uptake of PMNL-derived LTA4 by endothelial cells. The activation
      of the 5-lipoxygenase pathway in the context of tight interactions between blood
      cells and coronary vasculature, is suggested to have an important outcome in the
      alterations of coronary flow and cardiac contractility.

PMID- 8298811
TI  - Vascular responses to endothelin-1 following inhibition of nitric oxide synthesis
      in the conscious rat.
AB  - 1. The objectives of the present experiments were to assess the role of
      endogenous nitric oxide (NO) in mediating and/or modulating the effects of
      endothelin-1 (ET-1) on blood pressure and microvascular permeability in conscious
      rats. 2. Intravenous administration of the NO synthesis inhibitors, NG-monomethyl
      L-arginine (L-NMMA) or NG-nitro-L-arginine methyl ester (L-NAME) at a dose (25 mg
      kg-1 or 2 mg kg-1, respectively) which evoked maximum increase in mean arterial
      blood pressure (MABP) significantly attenuated (by about 40%) the vasodepressor
      response and potentiated (by 100-180%) the pressor response to ET-1 (1 nmol kg-1,
      i.v.) compared to the effects of ET-1 in animals where the peripheral
      vasoconstrictor effects of L-arginine analogues were mimicked by an infusion of
      noradrenaline (620-820 ng kg-1 min-1). Similar inhibition of the depressor and
      potentiation of the pressor actions of ET-1 were observed when the MABP which had
      been elevated by L-NMMA or L-NAME was titrated to normotensive levels with
      hydralazine or diazoxide before injection of ET-1. 3. L-NAME (2 mg kg-1)
      increased the vascular permeability of the large airways, stomach, duodenum,
      pancreas, liver, kidney and spleen (up to 280%) as measured by the extravasation
      of Evans blue dye. The permeability of pulmonary parenchyma, skeletal muscle and
      skin was not affected significantly by L-NAME treatment. Elevation of MABP by
      noradrenaline infusion did not evoke protein extravasation in the vascular beds
      studied with the exception of the lung. In the large airways, tissue Evans blue
      content was similar following noradrenaline infusion and L-NAME.4. Both the
      pressor and permeability effects of L-NAME (2 mg kg-1) were effectively reversed
      by L-arginine (300 mg kg- 1) but not by D-arginine (300 mg kg-1 ). The D
      enantiomer of L-NAME, D-NAME(2 mg kg-1) had no effect on the parameters
      studied.5. Protein extravasation was significantly enhanced by ET-1 (1 nmol kg-1)
      in the upper and lower bronchi, stomach, duodenum, kidney and spleen (up to
      285%). This was potentiated by L-NAME(2 mg kg-1), resulting in marked increases
      in tissue Evans blue accumulation (up to 550%) in these tissues. The effects of L
      NAME and ET-1 were additive in the trachea, duodenum, pancreas and liver.Combined
      administration of L-NAME plus ET-1 significantly increased protein extravasation
      in the pulmonary parenchyma, where neither L-NAME nor ET-1 alone caused
      significant increases.6. Noradrenaline infusion (620-820 ng kg-1 min-1)
      potentiated the permeability action of ET-1(1 nmol kg-1) in the pulmonary
      circulation, whereas it did not modify ET-1-induced protein extravasation in the
      other vascular beds.7. These results indicate that endogenous NO mediates, in
      part, the vasodepressor effect and attenuates the vasopressor action of ET-1 and
      modulates the effects of ET-1 on vascular permeability. These findings confirm
      the role of NO in the maintenance of blood pressure and suggest an important role
      for NO in the regulation of microvascular permeability.

PMID- 8298812
TI  - Attenuation by phentolamine of hypoxia and levcromakalim-induced abbreviation of
      the cardiac action potential.
AB  - 1. The effects of phentolamine (5-30 microM) and glibenclamide (10 microM) on
      action potential characteristics were examined in guinea-pig papillary muscle
      exposed to either hypoxia or levcromakalim (20 microM). 2. The hypoxia-induced
      abbreviation of action potential duration (APD) and effective refractory period
      (ERP) were attenuated but not abolished by glibenclamide (10 microM). Hypoxia
      reduced APD by 24 +/- 2 vs 65 +/- 4% in glibenclamide- and vehicle-treated
      tissue, respectively. 3. Phentolamine (10-30 microM) was less effective than
      glibenclamide in attenuating the hypoxic shortening of APD since APD was reduced
      by 38 +/- 10, 51 +/- 6% vs 65 +/- 4% in 10 and 30 microM phentolamine and vehicle
      treated muscle, respectively. 4. Phentolamine, at concentrations of 10 and 30
      microM, also reduced the upstroke velocity of the action potential and at 5
      microM it increased the APD from 193 +/- 9 to 221 +/- 12 ms. 5. Glibenclamide
      completely abolished and phentolamine (30 microM) significantly attenuated
      levcromakalim-induced changes in duration and ERP. Levcromakalim reduced APD by
      71 +/- 2 and 55 +/- 2% in control and phentolamine pretreated muscle,
      respectively. 6. It is concluded that phentolamine may block KATP channels at
      concentrations that also block sodium channels.

PMID- 8298813
TI  - Bradykinin initiates cytokine-mediated inflammatory hyperalgesia.
AB  - 1. The hyperalgesic activities in rats of bradykinin, carrageenin and
      lipopolysaccharide (LPS) were investigated in a model of mechanical hyperalgesia.
      2. Bradykinin and carrageenin evoked dose-dependent hyperalgesia with maximum
      responses of similar magnitude to responses to LPS (1 and 5 micrograms). 3. Hoe
      140, an antagonist of BK2 receptors, inhibited in a dose-dependent manner
      hyperalgesic responses to bradykinin, carrageenin and LPS (1 microgram) but not
      responses to LPS (5 micrograms), prostaglandin E2, dopamine, tumour necrosis
      factor alpha (TNF alpha), IL-1, IL-6 and IL-8. 4. Responses to bradykinin and LPS
      (1 and 5 micrograms) were inhibited by the cyclo-oxygenase inhibitor,
      indomethacin and by the beta-adrenoceptor antagonist, atenolol. The effects of
      indomethacin and atenolol were additive: their combination abolished responses to
      bradykinin and LPS (1 microgram) and markedly attenuated the response to LPS (5
      micrograms). 5. Antiserum neutralizing endogenous TNF alpha abolished the
      response to bradykinin whereas antisera neutralizing endogenous IL-1 beta, IL-6
      and IL-8 each partially inhibited the response. The combination of antisera
      neutralizing endogenous IL-1 beta+IL-8 or IL-6+IL-8 abolished the response to
      bradykinin. 6. Antisera neutralizing endogenous TNF alpha, IL-1 beta, IL-6 and IL
      8 each partially inhibited responses to LPS (1 and 5 micrograms). Increasing the
      dose of antiserum to TNF alpha or giving a combination of antisera to IL-1
      beta+IL-8 or IL-6+IL-8 further inhibited responses to LPS (1 and 5 micrograms).
      7. These data show that bradykinin can initiate the cascade of cytokine release
      that mediates hyperalgesic responses to carrageenin and endotoxin (1 microgram).
      The lack of effect of Hoe 140 on hyperalgesic responses to LPS (5 microgram)
      suggests that the release of hyperalgesic cytokines can be initiated
      independently of bradykinin BK2 receptors.

PMID- 8298814
TI  - Muscarinic regulation of cytosolic free calcium in canine tracheal smooth muscle
      cells: Ca2+ requirement for phospholipase C activation.
AB  - 1. The relationship between muscarinic receptor-mediated phosphatidylinositol 4,5
      bisphosphate (PIP2) breakdown and the increase of intracellular Ca2+ ([Ca2+])i
      has been examined in canine cultured tracheal smooth muscle cells (TSMCs). 2.
      Addition of acetylcholine (ACh) and carbachol led to a 2-3 fold increase in
      [Ca2+]i over the resting level as determined by fura-2, with half-maximal
      stimulation (EC50) obtained at concentrations of 97 and 340 nM, respectively.
      Addition of the partial agonist, bethanechol, showed a smaller increase in PIP2
      turnover and [Ca2+]i than did ACh or carbachol. 3. Addition of ACh or carbachol
      to TSMCs that had been prelabelled with [3H]-inositol led to the rapid (5-15 s)
      release of inositol mono, bis and trisphosphates IP1, IP2 and IP3. The time
      course of IP3 accumulation is correlated with the time course of the peak rise in
      [Ca2+]i. 4. Inclusion of EGTA lowered the resting [Ca2+]i and markedly reduced
      the extent of the agonist-induced rise in [Ca2+]i. When assayed under conditions
      similar to those used for the [Ca2+]i measurements, EGTA reduced the muscarinic
      agonist-stimulated inositol phosphates (IPs) accumulation. Conversely, ionomycin
      could stimulate IPs accumulation and elevate [Ca2+]i. The addition of Ca2+ (2.7
      617 nM) to digitonin-permeabilized TSMCs directly stimulated IPs accumulation. 5.
      Both Ca2+ and guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) stimulated the
      formation of IPs in digitonin-permeabilized TSMCs prelabelled with [3H]-inositol.
      A further calcium-dependent increase in IPs accumulation was obtained by
      inclusion of either GTP gamma S or carbachol. The combined presence of carbachol
      and GTP gamma S elicited a synergistic effect on IPs accumulation, with half
      maximal stimulation observed at approximately 8 nM free Ca2+.6. These results
      indicate that (i) the magnitude of the initial rise in [Ca2+], is directly
      related to the production of IPs and (ii) the phospholipase C-mediated PIP2
      breakdown in TSMCs is sensitive to regulation by physiologically relevant
      concentrations of free Ca2+ ([Ca2+]f).

PMID- 8298815
TI  - Characterization of the adenosine receptor mediating contraction in rat colonic
      muscularis mucosae.
AB  - 1. The objective of this study was to characterize the adenosine receptor
      mediating contraction in rat isolated colonic muscularis mucosae (RCMM). 2.
      Sequential additions of the adenosine receptor agonist 5'-N
      ethylcarboxamidoadenosine (NECA; 0.01-10 microM) elicited reproducible,
      concentration-related contractions in RCMM. The effects of NECA were mimicked by
      the adenosine A1 receptor-selective agonists cyclopentyladenosine (CPA), R
      phenylisopropyladenosine (R-PIA) and N-[1S, trans)2-hydroxycyclopentyl] adenosine
      (GR79236) and by S-PIA (the stereoisomer of R-PIA). The adenosine A2 agonists N
      [(2-methylphenyl)methyl] adenosine (metrifudil) and 2-[p-(2
      carboxyethyl)phenethylamine]-5'-N-ethylcarboxamidoadenosine (CGS21680) also
      produced contractions in RCMM but were 54 and 165 times less potent respectively
      than NECA. The rank order of agonist potency for contraction of RCMM was CPA > or
      = GR79236 = R-PIA > or = NECA > > S-PIA = metrifudil > CGS21680, which is
      identical to that reported for the inhibition of spontaneous rate in rat isolated
      right atria and inhibition of lipolysis in rat isolated adipocytes by these same
      agonists. 3. R-PIA, S-PIA and metrifudil behaved as partial agonists in RCMM. 4.
      The adenosine A1 receptor-selective antagonist 8-cyclopentyl-1,3-
      dipropylxanthine (DPCPX) inhibited the contractions produced by all the adenosine
      agonists tested, with pKB values between 9.2 and 9.5. The non-selective adenosine
      antagonist 8-phenyltheophylline (8-PT) antagonized the effects of NECA but also
      markedly potentiated (by 93.0 +/- 10.2% at 3 microM) the maximum contractile
      response to NECA in RCMM. Neither 8-PT (3 microM) nor DPCPX (0.1 microM) had any
      effect on the contractions produced by carbachol. 5. The contractile responses to
      NECA in RCMM were not affected by atropine (1 microM), tetrodotoxin(0.3 microM)
      or the P2 antagonist, suramin (100 microM).6. The present study confirms that
      contractions to adenosine agonists in the RCMM are mediated via adenosine Al
      receptors.

PMID- 8298816
TI  - Evidence for the involvement of a 5-HT4 receptor in the secretory response of
      human small intestine to 5-HT.
AB  - 5-Hydroxytryptamine increases transmucosal short-circuit current across human
      isolated small intestinal mucosa. The competitive 5-HT4 antagonist, DAU 6285
      evoked a concentration-dependent, dextral and parallel shift of the concentration
      response curve to 5-HT, with no alteration of the maximum response. Schild
      analysis of this antagonism produced a Schild regression with a slope of 1.00 and
      an apparent pA2 estimate of 6.17. It appears that a 5-HT4 receptor may mediate
      the short-circuit current response of human small intestinal mucosa to 5-HT.

PMID- 8298817
TI  - Vascular and anti-platelet actions of 1,2- and 1,3-glyceryl dinitrate.
AB  - 1. The aim of this study was to investigate whether two metabolites of glyceryl
      trinitrate (GTN), 1,2 and 1,3-glyceryl dinitrate (1,2-GDN and 1,3-GDN) could
      account for the pharmacological effects of GTN. To this end the formation of
      nitric oxide (NO) from 1,2- and 1,3-GDN in the presence of bovine aortic smooth
      muscle cells (SMC) or endothelial cells (EC) was studied. The effects of various
      thiols on NO formation from these dinitrates was also evaluated. 2. 1,2-GDN or
      1,3-GDN (10(-10)-10(-5) M) caused a dose-dependent relaxation of rabbit aortic
      strips denuded of endothelium and precontracted with phenylephrine. The
      dinitrates were less than one tenth as potent as GTN. 3. Incubation of 1,2-GDN or
      1,3-GDN (75-2400 microM) with SMC for 30 min led to a concentration-dependent
      increase in nitrite (NO2-) formation but this increase was less than that
      produced from GTN. Likewise incubation of 1,2-GDN or 1,3-GDN with N
      acetylcysteine (NAC), glutathione (GSH) or thiosalicylic acid (TSA) (all at 1 mM)
      for 30 min at 37 degrees C produced a concentration-dependent increase in NO2-
      formation. 4. Platelet aggregation induced by thrombin (40 mu ml-1) was not
      modified by high concentrations of 1,2-GDN or 1,3-GDN (175-700 microM). However,
      aggregation was inhibited when platelets were exposed to 1,2-GDN or 1,3-GDN (700
      microM) in the presence of SMC (0.24-1.92 x 10(5) cells) or EC (0.8-3.2 x 10(5)
      cells). These effects were abrogated by co-incubation with oxyhaemoglobin (OxyHb,
      10 microM) indicating that they were due to NO release. The concentrations of the
      dinitrates required to inhibit platelet aggregation by 50% were about 15 times
      higher than for GTN in the presence of the same numbers of SMC or EC.5. When NAC
      or TSA (both at 0.5 mM) were co-incubated with platelets for 3 min in the
      presence of1,2-GDN or 1,3-GDN, a concentration-dependent inhibition of platelet
      aggregation was observed. These anti-platelet effects were abolished by co
      incubation with OxyHb (10 microM). Glutathione had no potentiating effects.6.
      Thus the dinitrate metabolites of GTN are metabolized to NO by SMC or EC and are
      acted upon by thiols to form NO at concentrations about 10 times higher than
      those of GTN. In vivo, after oral or intravenous GTN, GDN levels are reached
      which are more than 10 times higher than those of GTN.These data support the
      notion that part of the effects of GTN are due to the generation of NO from 1,2
      GDN and 1,3-GDN by the cells of the vascular wall.

PMID- 8298818
TI  - Study of the mechanism of the relaxant action of (+)-glaucine in rat vas
      deferens.
AB  - 1. Effects of the aporphinoid alkaloid, (+)-glaucine, on rat vas deferens were
      investigated. 2. (+)-Glaucine (2-18 microM) competitively inhibited contractions
      induced by noradrenaline and methoxamine with a pA2 value of about 6. 3. (+)
      Glaucine (2 and 18 microM) did not change the accumulation of tritium during
      incubation of the vas deferens with [3H]-noradrenaline. 4. (+)-Glaucine (0.3 nM
      0.1 mM) inhibited specific [3H]-prazosin binding to membranes from rat vas
      deferens with a pKi value of 6.63, which is close to the pA2 value obtained
      against noradrenaline and methoxamine in functional studies. 5. In electrically
      stimulated rat vas deferens, (+)-glaucine (0.3-10 microM) enhanced twitch
      contractions and competitively antagonized the inhibitory effect of clonidine
      with a pA2 value of 5.91. 6. In tissues incubated in depolarizing calcium-free
      high-potassium medium, (+)-glaucine (30-80 microM) inhibited Ca(2+)-induced
      contractions with depression of the maximal response at higher doses and with a
      pD'2 value of 3.65. Furthermore, (+)-glaucine (50 microM) did not modify basal
      45Ca uptake but strongly inhibited the influx of 45Ca induced by K+. 7. These
      results suggest that (+)-glaucine has non-selective alpha 1- and alpha 2
      adrenoceptor blocking properties. At higher doses, (+)-glaucine shows calcium
      antagonist activity which may be responsible, at least in part, for the
      inhibition of the contractions induced by Ca2+ in calcium-free high-potassium
      medium.

PMID- 8298819
TI  - Adenosine receptor-mediated modulation of acetylcholine release from rat striatal
      synaptosomes.
AB  - 1. The effects of A1 and A2a adenosine receptor agonists on the veratridine
      evoked release of [3H]-acetylcholine ([3H]-ACh) from rat striatal synaptosomes
      was investigated by use of the A1-selective agonist, R-PIA and the 185 fold
      selective A2a agonist, CGS 21680. The effects of NECA, which is equipotent at
      both receptor subtypes, were also studied. 2. The evoked release of [3H]-ACh was
      significantly enhanced by the A2a agonist CGS 21680 but decreased by the A1
      agonist, R-PIA. The effects of NECA were dependent on the concentration used,
      with high concentrations inhibiting and low concentrations enhancing the evoked
      release of [3H]-ACh. In the absence of any antagonists, the rank order of potency
      for these three drugs on increasing [3H]-ACh release was CGS 21680 > NECA > R
      PIA. 3. The stimulatory effects of CGS 21680 and low NECA concentrations on
      evoked [3H]-ACh release were antagonized by the A2a receptor antagonists,
      CP66,713 (300 nM) and CGS 15943A (50 nM) whilst the inhibitory effects of R-PIA
      were reversed by the selective A1 antagonist, DPCPX (4 nM). In the presence of
      DPCPX, NECA greatly enhanced the evoked release of [3H]-ACh at all concentrations
      studied when, during such A1 receptor blockade, the rank order of potency was
      NECA >> CGS 21680 > R-PIA. 4. These results demonstrate that both A1 and A2a
      adenosine receptors modulate the veratridine-evoked release of [3H]-ACh from rat
      striatal synaptosomes.

PMID- 8298820
TI  - Comparison of the effects of EXP3174, an angiotensin II antagonist and
      enalaprilat on myocardial infarct size in anaesthetized dogs.
AB  - 1. In order to determine whether the renin-angiotensin system is involved in
      myocardial ischaemia-reperfusion injury, we investigated and compared the effects
      on infarct size of two different drugs which interfere with this system, i.e., an
      angiotensin II (AT1) antagonist, EXP3174, and an angiotensin I-converting enzyme
      inhibitor (ACEI), enalaprilat in a canine model of ischaemia-reperfusion. 2.
      EXP3174 (0.1 mg kg-1, i.v. followed by 0.02 mg kg-1 h-1 for 5.5 h) and
      enalaprilate (0.3 mg kg-1, i.v. followed by 0.06 mg kg-1 h-1 for 5.5 h) were used
      in doses inducing a similar level of inhibition (87 +/- 4 and 91 +/- 3%,
      respectively) of the pressor responses to angiotensin I. Control animals received
      saline. 3. Infarct size and area at risk were quantified by ex vivo dual coronary
      perfusion with triphenyltetrazolium chloride and monastral blue dye. Regional
      myocardial blood flows (ischaemic and nonischaemic, endocardial, epicardial) were
      assessed by the radioactive microsphere technique. 4. Both EXP3174 and
      enalaprilat induced a decrease in mean arterial blood pressure. However, non
      significant changes in regional myocardial blood flows, whether ischaemic or
      nonischaemic, were observed after administration of either the ACEI or the AT1
      antagonist. 5. The size of the area at risk was similar in the three groups. By
      direct comparison, there were no significant differences between infarct sizes in
      the three groups. Furthermore, there was a close inverse relationship between
      infarct size and transmural mean collateral blood flow in controls, and none of
      the treatments altered this correlation. Thus, neither EXP3174 nor enalaprilat
      limited infarct size. 6. These results indicate that activation of the renin
      angiotensin system does not contribute to myocyte death in this canine
      ischaemia/reperfusion model.

PMID- 8298821
TI  - Time-related increases in cardiac concentrations of doxorubicinol could interact
      with doxorubicin to depress myocardial contractile function.
AB  - 1. The present study evaluated the time-dependency of acute anthracycline
      cardiotoxicity by varying the duration of exposure of rabbit isolated atria to
      doxorubicin and determining changes (1) in contraction and relaxation and (2) in
      atrial concentrations of doxorubicin and its C-13 hydroxy metabolite,
      doxorubicinol. 2. Following addition of doxorubicin (175 microM) to atria,
      contractility (dF/dt), muscle stiffness (resting force, RF) and relaxation (90%
      relaxation time, 90% RT) were monitored for a 3.5 h period. 3. Doxorubicin (175
      microM) progressively diminished mechanical function (decreased dF/dt, increased
      RF and prolonged 90% RT) over 3 h. Doxorubicinol (1.8 microM), however, failed to
      produce time-related cardiac dysfunction; it depressed contractile function and
      increased muscle stiffness during the first 30 min without causing additional
      cardiac dysfunction during the remaining 3 h of observation. Doxorubicinol had no
      effect on 90% RT. 4. During treatment with doxorubicin, atria contained
      considerably more doxorubicin than doxorubicinol (ratio of doxorubicin to
      doxorubicinol ranged from 778 to 74 at 0.5 and 3 h, respectively). Elevations of
      doxorubicin and doxorubicinol in atria paralleled the degree of dysfunction of
      both contraction and relaxation; increases in muscle stiffness, however, were
      more closely associated with increases of doxorubicinol than doxorubicin. 5. To
      probe the relation between cardiac doxorubicinol and myocardial dysfunction
      further, without confounding effects of cardiac doxorubicin, concentration
      response experiments with doxorubicinol (0.9-7.2 microM) were conducted. 6. Plots
      of doxorubicinol concentrations in atria vs contractility indicated that the
      cardiac concentration of doxorubicinol, at which contractility is reduced by 50%,
      is five fold lower in doxorubicin-treated than in doxorubicinol-treated
      preparations. Thus, doxorubicin and doxorubicinol appear to interact to depress
      contractile function.7. Cardiac concentrations of both doxorubicin and
      doxorubicinol, as observed in these studies, were found to stimulate markedly
      Ca2+ release from isolated SR vesicles, but 3 microM doxorubicinol promoted a 15
      fold greater release rate than 3 microM doxorubicin.8. Our observations coupled
      with the previously reported finding that doxorubicinol inhibits Ca2+loading of
      SR, suggests that doxorubicinol accumulation in heart contributes to the time
      dependent component of doxorubicin cardiotoxicity, through a mechanism that could
      involve perturbations of Ca2+ homeostasis.

PMID- 8298822
TI  - Intracellular calcium in canine cultured tracheal smooth muscle cells is
      regulated by M3 muscarinic receptors.
AB  - 1. The regulation of cytosolic Ca2+ concentrations ([Ca2+]i) during exposure to
      carbachol was measured directly in canine cultured tracheal smooth muscle cells
      (TSMCs) loaded with fura-2. Stimulation of muscarinic cholinoceptors (muscarinic
      AChRs) by carbachol produced a dose-dependent rise in [Ca2+]i which was followed
      by a stable plateau phase. The EC50 values of carbachol for the peak and
      sustained plateau responses were 0.34 and 0.33 microM, respectively. 2. Atropine
      (10 microM) prevented all the responses to carbachol, and when added during a
      response to carbachol, significantly, but not completely decreased [Ca2+]i within
      5 s. Therefore, the changes in [Ca2+]i by carbachol were mediated through the
      muscarinic AChRs. 3. AF-DX 116 (a selective M2 antagonist) and 4-diphenylacetoxy
      N-methylpiperidine (4-DAMP, a selective M3 antagonist) inhibited the carbachol
      stimulated increase in [Ca2+]i with pKB values of 6.4 and 9.4, respectively,
      corresponding to low affinity for AF-DX 119 and high affinity for 4-DAMP in
      antagonizing this response. 4. The plateau elevation of [Ca2+]i was dependent on
      the presence of external Ca2+. Removal of Ca2+ by the addition of 2 mM EGTA
      caused the [Ca2+]i to decline rapidly to the resting level. In the absence of
      external Ca2+, only an initial transient peak of [Ca2+]i was seen which then
      declined to the resting level; the sustained elevation of [Ca2+]i could then be
      evoked by the addition of Ca2+ (1.8 mM) in the continued presence of carbachol.
      5.Ca2+ influx was required for the changes of [Ca2+]i, since the Ca2+-channel
      blockers, diltiazem(10 microM), nifedipine (10 microM), verapamil (10 microM) and
      Ni2+ (5 mM), decreased both the initial and sustained elevation of [Ca2+], in
      response to carbachol. These Ca2+-channel blockers also decreased the sustained
      elevation of [Ca2+], when applied during the plateau phase.6. In conclusion, we
      have demonstrated that the initial detectable increase in carbachol
      stimulated[Ca2+]J is due to the release of Ca2+ from internal stores, followed by
      the flux of external Ca2+ into the cells. This influx of extracellular Ca2+
      partially involves an L-type Ca2+-channel. M3 muscarinic receptors appear to
      mediate the Ca2+ mobilization in canine TSMCs.

PMID- 8298823
TI  - Brain, mind and behaviour. Some medico-legal aspects.
AB  - The advent of new imaging techniques is broadening our understanding of the major
      psychiatric illnesses. The increased knowledge of brain function will have
      consequences for the expert medical witness who has to give evidence in court.
      Both the insanity defence and the defence of automatism depend on disorders of
      the mind. Psychiatry is now able in many cases to produce evidence that these are
      consequent upon disorders of the brain. In presenting evidence in court there is
      an apparent conflict between 'brain words' and 'mind words'.

PMID- 8298824
TI  - Predictors of response to lithium and triiodothyronine augmentation of
      antidepressants in tricyclic non-responders.
AB  - Although both lithium and triiodothyronine (T3) augmentation strategies may be
      rapid, safe, and effective ways of treating patients who fail to respond to
      tricyclics, little is known about the clinical or biochemical correlates of
      response. We examined clinical and endocrine variables which distinguished T3 and
      lithium responders from each other and from non-responders in a post-hoc analysis
      of two studies involving 51 subjects who had received these augmentation
      strategies under double-blind conditions. Lithium non-responders were more
      severely depressed and had more insomnia and weight loss than responders. T3
      responders could be distinguished from lithium responders by greater weight loss.
      There were no reliable clinical differences between T3 responders and non
      responders. Thyroid function tests did not differ between any of the treatment or
      response groups. Our findings suggest that clinical but not endocrine variables
      may distinguish responders to these two augmentation strategies.

PMID- 8298825
TI  - The South London Somatisation Study. I: Longitudinal course and the influence of
      early life experiences.
AB  - In a two-year longitudinal study, a two-stage screening procedure was used to
      identify subjects in primary care with emotional disorder presenting with a
      recent onset of physical symptoms and a comparison sample of patients presenting
      with physical symptoms only. Somatisers (n = 44) were defined as subjects who had
      an emotional disorder but who presented with physical symptoms that could not be
      attributed to organic disease. The course and outcome of these conditions were
      compared with those of pure emotional disorder (n = 11), pure physical disorder
      (n = 90) and 'mixed' conditions (n = 39). The physical symptoms of somatisers
      were less likely to improve and lagged behind those of the other groups, and 16
      of these acute somatisers went on to develop chronic somatoform disorders. Among
      somatisers, changes in physical symptom levels throughout the follow-up closely
      mirrored changes in emotional arousal. Emotionally disordered subjects reported
      more instances of parental lack of care, but somatisers were also more likely
      than other groups to report parental physical illness and to have had more
      physical illness themselves in childhood. A logistic regression suggests that
      adult somatisation is best modelled by parental lack of care followed by
      childhood illness.

PMID- 8298826
TI  - Prognosis of depression in the elderly. A comparison with younger patients.
AB  - The prognosis of depression in the elderly was investigated in a mixed-age sample
      of 242 consecutive referrals, with DSM-III defined unipolar major depressive
      episode, to a specialist unit for mood disorders. Subjects were followed up at
      about 1 and 3.8 years. There was no significant difference in outcome between
      younger (under 40 years), middle aged (40-59 years) and older (60 years or more)
      depressed patients. For the 61 elderly subjects with depression, prognosis
      improved with time, with 25% having a lasting recovery at the first and 41% at
      the second follow-up. Early onset, recurrence, and poor premorbid personality
      were associated with a worse prognosis. Three (5%) elderly depressives had
      committed suicide and seven (11%) had died from natural causes by the second
      follow-up. Despite some methodological limitations, our findings suggest a more
      optimistic outlook and the need for longer, more assertive treatment for elderly,
      depressed patients.

PMID- 8298827
TI  - Single photon emission computerised tomography in elderly patients with
      Alzheimer's disease and multi-infarct dementia. Regional uptake of technetium
      labelled HMPAO related to clinical measurements.
AB  - Single photon emission computerised tomography (SPECT) was used to measure
      regional brain uptake of technetium-99m hexamethylpropyleneamine oxine (Tc99m
      HMPAO) in elderly patients with Alzheimer's disease (AD), multi-infarct dementia
      (MID) and normals (n = 20 in each group). Different patterns of uptake were found
      between groups when cortical uptake was normalised to cerebellar uptake.
      Reductions occurred in all regions in AD, being most marked in temporal and
      posterior parietal areas. Significant correlations were found in AD between
      memory impairment and decreased temporal uptake bilaterally, and between duration
      of illness and reduced uptake in most brain regions. MID patients showed higher
      uptake in the anterior parietal region than did the other groups. A variable
      comparing anterior to posterior uptake significantly discriminated the two
      patient groups.

PMID- 8298828
TI  - Computerised tomography in newly diagnosed schizophrenia and schizophreniform
      disorder. A controlled blind study.
AB  - Patients with newly diagnosed schizophrenia (n = 27) or schizophreniform disorder
      (n = 22) and 24 healthy volunteers were investigated by CT scan, the
      investigators being blind to subject status. The patients had never received
      medication or had been treated only briefly with neuroleptics. The patients had
      significantly smaller brain volume and brain length than the controls. The
      patients had greater sulcal enlargement in the case of both Sylvian and
      interhemispheric fissures and surface sulci in the frontal and parietal regions.
      The sulcal enlargement was more pronounced in male patients and on the left
      hemisphere. The study revealed no enlargement of the lateral ventricles and only
      a trend towards enlargement of the third ventricle in the patients. The findings
      were not explained by substance abuse or level of education.

PMID- 8298829
TI  - Schizophrenia in Nottingham: lifelong residential mobility of a cohort.
AB  - The lifetime geographical mobility of a group of 67 patients suffering from
      schizophrenia was investigated and related to the ecological structure of the
      city of Nottingham, where they first presented between 1978 and 1980. The study
      aimed to investigate the processes leading to a threefold rate of schizophrenia
      in the most socioeconomically deprived area of the city compared to the area of
      least deprivation. Results suggest that this skewed distribution begins early in
      the lives of the patients and is well established at least five years before
      initial contact with the psychiatric services.

PMID- 8298830
TI  - Persistence of the decline in the diagnosis of schizophrenia among first
      admissions to Scottish hospitals from 1969 to 1988.
AB  - Age-standardised rates were calculated for first admissions to hospital in
      Scotland with ICD-9 diagnoses of schizophrenia, affective psychoses, paranoid
      psychoses, reactive psychoses and depressive neuroses (ICD-9 295, 296, 297, 298
      and 300.4) for the period 1969-88. First-admission rates for schizophrenia
      declined by an average of 3.3% per year in males and 4.4% per year in females
      over the period. The first-admission rate in males in 1988 was 8.4/100,000 (57%
      of 1969 rate) and in females was 4.8/100,000 (43% of 1969 rate). Rates for
      depressive neuroses, affective psychoses, reactive psychoses and combined
      psychoses also fell. Rates for mania rose, as did those for paranoid states in
      males. The decrease in first-admission rates is likely to reflect a true decrease
      in the incidence of schizophrenia over the period. The decline was unlikely to be
      accounted for by diagnostic change because there was no reciprocal increase in
      any other diagnosis sufficient to account for the change, and the rates for
      combined psychoses also decreased. There was evidence that rates for
      schizophrenia declined to a greater extent in younger age groups, especially in
      females. This could imply the presence of a birth cohort effect.

PMID- 8298831
TI  - Risk of schizophrenia and age difference with older siblings. Evidence for a
      maternal viral infection hypothesis?
AB  - Recent reports that some influenza epidemics may be followed by a transient
      increase in the births of schizophrenic patients have led to the hypothesis that
      maternal viral infections contribute to the aetiology of schizophrenia. It is
      well known that respiratory viral infections are frequently brought into the home
      by young children. We tested the predictions that the risk of schizophrenia is
      decreased in first-born children, and increased in individuals who had siblings
      of a young age while in utero, using data from a Swedish family study. Our
      results are consistent with these predictions. In particular, having siblings
      three to four years older was associated with a significantly increased risk of
      schizophrenia, even after allowing for birth order, sibship size, and other
      potential confounders. If replicated, these results provide indirect support for
      the maternal viral infection hypothesis, although there are alternative
      explanations.

PMID- 8298832
TI  - Remands and psychiatric assessments in Holloway Prison. I: The psychotic
      population.
AB  - Remand prisoners diagnosed as psychotic by Holloway's psychiatrists were followed
      up to time of sentence. Most were referred to outside psychiatrists and then
      offered beds. Courts invariably enabled the beds to be used. Few women had
      committed serious offences, and most had been remanded because the courts thought
      they needed help. The study showed custodial remands to be an unsatisfactory way
      of seeking treatment for psychotic offenders. Alternatives need to be developed
      urgently. For psychotic people who continue to be remanded in custody, transfers
      rather than court orders should initially be used to effect admission.

PMID- 8298833
TI  - Remands and psychiatric assessments in Holloway. Prison II: The non-psychotic
      population.
AB  - Non-psychotic remand prisoners who were referred by Holloway's doctors to outside
      psychiatrists, or who were the subject of court reports, or who were diagnosed as
      mentally handicapped, were followed up to the time of sentence. Most of the
      referred women were minor offenders with diagnoses of mental handicap or
      personality disorder. They were usually refused beds on treatability criteria and
      then released with non-custodial sentences. Some were highly disturbed, and it
      seemed that the police who charged them, the courts who remanded them and the
      prison psychiatrists who referred them, all found it hard to accept that
      psychiatry had so little to offer these people. Local health and social services
      need to address the problems raised by this small group of women. Arsonists more
      often obtained beds than minor offenders, and were likely to be imprisoned when
      hospital places were not forthcoming.

PMID- 8298834
TI  - Postnatal emotional disorders in Nigerian women. A study of antecedents and
      associations.
AB  - One hundred and sixty-two women were evaluated for psychiatric morbidity in the
      second trimester of pregnancy and also six to eight weeks postnatally. A sizeable
      proportion of the women also had a second prenatal assessment in their third
      trimester and in the lying-in ward shortly after giving birth. Assessments were
      conducted with the 28-item GHQ. This was initially validated using a subsample of
      106 women, taken from the original group, who were interviewed with the PAS.
      Thirty per cent of the women were 'cases' at the first prenatal assessment, while
      only 14% were 'cases' six to eight weeks postnatally. Thus, even though there was
      an overlap between prenatal and postnatal morbidity, there was also substantial
      difference between the groups that were symptomatic at both periods. This
      observation was reinforced by the low correlation between the mean GHQ scores at
      both periods. Both prenatal and postnatal morbidities were associated with recent
      adverse life events, with the latter more likely to be associated with marital
      and family events. This observation is in support of the view that neurotic
      problems, prenatally or postnatally, are caused mainly by psychosocial factors.

PMID- 8298835
TI  - The psychosocial impact of HIV infection in gay men, drug users and
      heterosexuals. Controlled investigation.
AB  - The aim of this study was to establish the prevalence of current and past
      psychiatric morbidity in HIV seropositive asymptomatic subjects belonging to
      three transmission categories (gay men, intravenous drug users, and
      heterosexuals) compared with that found in HIV seronegative controls from the
      same groups. A cross-sectional, controlled study including 279 seropositive
      subjects belonging to groups II and III defined by the Center for Disease Control
      (94 gay men, 157 intravenous drug users, and 28 heterosexuals) and 159
      seronegative subjects (38 gay men, 91 intravenous drug users, and 30
      heterosexuals) is reported. Outcome measures included standardised, self-report
      questionnaires and a semistructured interview to assess current
      psychopathological status and past psychiatric history. In addition, a
      psychiatric diagnosis according to DSM-III-R criteria Axis I and II was made in
      the seropositive subjects. Results showed that these subjects differed very
      little from the controls and that overall levels of psychiatric disturbances in
      both groups were low and similar to those found in other life-threatening
      illnesses. Furthermore, intravenous drug users, regardless of HIV serological
      status, had the highest levels of psychological morbidity. Psychosocial distress
      was associated with previous and current lifestyle, independently of HIV status.

PMID- 8298836
TI  - Screening and psychological debriefing of adolescent survivors of life
      threatening events.
AB  - There is a perceived need for schools and casualty departments to receive
      appropriate information and guidelines in order to minimise the effect of PTSD. A
      recommended screening battery for PTSD was administered at the start of a two
      session debriefing group and again three months later to a group of seven young
      survivors of a minibus accident. No studies using this screen other than those of
      shipping disasters have been reported to date. Screen scores were compared with
      those of survivors of the cruise ship Jupiter. No significant differences were
      found between minibus survivors when assessed at six months (before
      intervention), and Jupiter survivors, who when assessed at five months had
      already undergone debriefing. Post-debriefing assessment of minibus survivors
      demonstrated significant reductions on all measures.

PMID- 8298837
TI  - Fowkes et al's "Serum cholesterol, triglycerides, and aggression in the general
      population".
AB  - "A higher than expected number of violent deaths and suicides in coronary
      prevention trials has provoked interest in the possibility that low serum
      cholesterol concentrations are associated in the general population with
      personality characteristics predisposing to aggressive and suicidal behaviour. We
      have investigated this possibility in the Edinburgh Artery Study. We measured
      serum lipid concentrations in blood samples taken from fasting subjects and
      assessed personality characteristics on the Bedford Foulds Personality Deviance
      Scales in a random sample of 1,592 men and women aged 55-74 years, selected from
      age-sex registers of ten general practices in Edinburgh. Serum cholesterol
      concentration was not significantly associated with aggression in men, but it was
      associated in multivariate analysis (though not univariate analysis) with
      denigratory attitudes towards others among women. However, serum triglyceride
      concentration was related, especially in men, to hostile acts (r = 0.13, P <
      0.001) and domineering attitude (r = 0.12, P < 0.001) independently of age, total
      and HDL cholesterol, cigarette smoking, and alcohol consumption. Subjects taking
      part in prevention trials have higher triglyceride concentrations than the
      general population and the relation between serum triglyceride concentration and
      aggression merits further investigation."

PMID- 8298838
TI  - State-dependent pain in winter depression.
AB  - The incidence and nature of state-dependent pain were investigated in 43
      consecutively presenting patients with recurrent autumn/winter episodes of major
      depression followed by spontaneous recovery in the spring. Twenty-two (51.2%)
      experienced state-dependent pain, which appears to be a common concomitant of
      wintertime depression.

PMID- 8298839
TI  - Handedness in mental handicap: investigation into populations of Down's syndrome,
      epilepsy and autism.
AB  - The handedness in three randomly sampled groups of people with learning
      disabilities consisting of patients with Down's syndrome, epilepsy, and autism
      were studied using a validated instrument. All subjects were controlled for
      neurological and other medical disorders. A statistically significant increase in
      left-handedness and ambiguous handedness compared with the general population was
      found in all groups. There was no significant difference in the rate of left
      handedness between the three groups.

PMID- 8298840
TI  - Psychiatric presentation of a third ventricular colloid cyst in a mentally
      handicapped woman.

PMID- 8298841
TI  - Mania following sleep deprivation.
AB  - A first episode of mania is described in a previously healthy man who was
      partially sleep deprived for four nights. The sleep deprivation preceded the
      psychosis. During the psychotic episode he believed that he was the Messiah. This
      case is discussed in the light of reports exploring the relationship between
      psychosis and sleep deprivation.

PMID- 8298842
TI  - Prader-Willi syndrome and psychoses.
AB  - Prader-Willi syndrome (PWS) is associated with an insatiable appetite and (often)
      other maladaptive behaviours (self-injury, sleep disorders, insistence on
      routines, and temper tantrums). Psychoses are not a recognised feature. Most
      affected people have a chromosome 15 abnormality (deletion, disomy, structural
      rearrangement, etc.). Three people with PWS who developed psychotic disorders in
      early adult life are described. The nature of the psychoses and the significance
      of the association are discussed.

PMID- 8298843
TI  - Long-term, high-dose disulfiram in the treatment of alcohol abuse.
AB  - A patient who had experienced most of the standard methods of managing alcohol
      abuse found that during 11 years of treatment, the most consistently effective
      intervention has been the taking of disulfiram under family supervision. He has
      received 600 mg daily almost continuously for over six years without side
      effects. Smaller doses do not have an adequate deterrent effect.

PMID- 8298844
TI  - Bipolar disorder following a left basal-ganglia stroke.

PMID- 8298845
TI  - Recruitment for post-natal depression studies.

PMID- 8298846
TI  - Tricyclic-induced seizures and absent ECT response.

PMID- 8298847
TI  - Lithium toxicity at therapeutic serum levels.

PMID- 8298848
TI  - Psychiatric morbidity in the relatives of schizophrenic probands.

PMID- 8298849
TI  - Catatonia: the tension insanity.

PMID- 8298850
TI  - Low serum cholesterol and suicide.

PMID- 8298851
TI  - Eye-movement desensitisation to overcome post-traumatic stress disorder.

PMID- 8298852
TI  - How well are 'cured' anorexic nervosa patients?

PMID- 8298853
TI  - Psychiatric symptoms in cannabis users.

PMID- 8298854
TI  - Fluoxetine--induced mania in a patient with post-stroke depression.

PMID- 8298855
TI  - Relapse following withdrawal of drug addiction.

PMID- 8298856
TI  - Percutaneous endoscopic gastrostomy and severe endogenous depression.

PMID- 8298857
TI  - Effect of disorientation on visual analysis, familiarity decision and semantic
      decision on faces.
AB  - The disproportionate effect of vertical inversion on the processing of faces has
      often been interpreted as indicating differences in perceptive strategies between
      upright and inverted faces. If this is true, then the mathematical relation
      between the performance and the angular deviation would not be a linear function.
      Thirty subjects processed faces shown under 10 angular deviations from upright (0
      deg) to upside-down (180 deg) in steps of 20 degrees, in a random design. Three
      cognitive levels (a between-subject factor) were tested, namely, gender
      classification of unfamiliar faces, familiarity decision on famous vs. unknown
      faces, and semantic decision (occupation) on famous faces, with 480 items per
      subject and task. We found no sign of a change of processing strategies for the
      upright vs. inverted presentations: a clear linear function emerged. However, the
      nature of the task could influence the effect of the angular deviation on the
      performance. Results suggest that, up to now, there is no definite proof of
      qualitatively different mechanisms underlying the processing of upright and
      inverted faces, respectively.

PMID- 8298858
TI  - Measuring locus of control: a critique of general, children's, health- and work
      related locus of control questionnaires.
AB  - This paper attempts a critical review not so much of the concept of locus of
      control as the plethora of unidimensional or sphere-specific measures that have
      been developed in the past 25 years. After a brief history of the development of
      the concept of locus of control, various oft-repeated and some new criticisms are
      considered. One frequent response to problems associated with the original
      concept and scale has been to develop new psychometrically validated, sphere- or
      topic-specific measures. These are tabulated and reviewed under five headings:
      measures (either multidimensional or sphere-specific) of the general concept of
      locus of control; measures devised specifically for children and adolescents;
      measures that have concentrated on aspects of mental and physical health; work,
      career and economic locus of control measures; and finally, measures which have
      extended the locus of control concept into other areas. The advantages and
      disadvantages of this proliferation of measures is considered in some detail,
      especially the issue of incremental validity, and recommendations are made for
      future work in this area.

PMID- 8298859
TI  - Annett's theory that individuals heterozygous for the right shift gene are
      intellectually advantaged: theoretical and empirical problems.
AB  - Annett & Manning (1989; 1990a,b) have proposed that left-handedness is maintained
      by a balanced polymorphism, whereby the rs+/-heterozygote manifests increased
      intellectual ability compared with the rs-/- and rs+/+ homozygotes. In this paper
      we demonstrate that Annett's method of dividing subjects into putative genotypes
      does not allow the rs+/- genotype to be compared with the rs-/- genotype within
      handedness groups. Our alternative method does allow heterozygous right-handers
      to be compared both with rs+/+ and rs-/- homozygotes. Using this method in
      undergraduates we find no evidence that supposed heterozygotes are relatively
      more intellectually able than homozygotes on tests of verbal IQ, spatial IQ,
      diagrammatic IQ or vocabulary. Theoretical analysis of the balanced polymorphism
      hypothesis reveals additional limitations. Although estimation of the size of the
      heterozygote advantage suggests that it must be very large (21 or 45 IQ points)
      to explain the effects found by Annett & Manning, it nevertheless must be very
      small (3.4 IQ points) to be compatible with the known differences between right-
      and left-handers in social class and intelligence. Moreover power analysis shows
      that the latter effect size is too small for Annett & Manning to have found
      effects in their studies. Additional power analyses show that studies looking for
      effects in groups of high intellectual ability, such as university students, are
      incapable of finding significant results, despite Annett claiming such effects.
      If the Annett & Manning paradigm does demonstrate differences in intellectual
      ability related to skill asymmetry then those differences are unlikely to result
      from a balanced polymorphism, but instead probably reflect motivational or other
      differences between right-handers of high and low degrees of laterality.

PMID- 8298860
TI  - The handedness of Kerrs and Carrs.
AB  - The surnames Kerr and Carr have been claimed, on the basis of folkloric and
      etymological evidence, to be associated with an increased incidence of left
      handedness. In 1974 a survey by the Royal College of General Practitioners
      suggested that the incidence of left-handedness was nearly three times as high in
      Kerr/Carr families as in controls. That survey was however potentially flawed by
      response biases. In the present study, which used better controls, no evidence
      was found for an increased incidence of left-handedness in Kerrs and Carrs.

PMID- 8298861
TI  - Clinical diagnosis from digital displays: results and conclusions from the St
      Mary's evaluation project.
AB  - Preliminary results with the first commercially available digital display system
      to be installed in a British radiology department were published in 1989: these
      consisted of data from observer performance studies of digitized images displayed
      using a 1024-line monitor, showing a single pathological feature--subperiosteal
      resorption in renal osteodystrophy. Further experiments have now been conducted
      with the successor to this equipment, a 1280-line digital display system. Formal
      observer performance studies were undertaken for four pathological conditions,
      and the results show statistically significant differences in performance between
      the digitized displayed images and those on film. The display system was not
      considered to be good enough for the task of primary radiological diagnosis of
      subtle lesions; findings support the conclusion that careful, objective clinical
      evaluation of digital display systems is important before they are introduced
      into clinical use.

PMID- 8298862
TI  - Case report: ureteric obstruction secondary to contralateral hydronephrosis.
AB  - Giant hydronephrosis is a rare condition, defined in the adult as a kidney
      containing more than 1 l of fluid. It is usually secondary to pelvi-ureteric
      junction obstruction. We describe a case where giant hydronephrosis caused
      contralateral ureteric obstruction. The radiological findings are described and
      the literature is reviewed.

PMID- 8298863
TI  - Case report: radiological appearances in peliosis hepatis.
AB  - Peliosis hepatis is an unusual disorder characterized by blood filled hepatic
      spaces. We describe the appearances of this entity on ultrasonography, computed
      tomography and magnetic resonance imaging. The importance of peliosis hepatis is
      that it may be an indicator of a treatable underlying condition.

PMID- 8298864
TI  - Case of the month: the case of the knotty string.

PMID- 8298865
TI  - Short communication: helical computed tomography: where is the cut?
AB  - The helical scanning mode in computed tomography (CT) entails continuous table
      movement during image acquisition. The projections acquired in this mode will not
      be consistent with those in the axial scanning mode. A comparison of the helical
      and axial modes of scanning on the IGE HiSpeed Advantage CT system (software
      version ZA) has been made using a contrast-detail phantom. Differences seen
      between the two modes include shadow and streaking artefacts and an increase in
      the partial volume effect in the helical scan mode.

PMID- 8298866
TI  - Evaluation of tilted, optimized, non-saturating excitation pulses in 3D magnetic
      resonance angiography of the abdominal aorta and major branches in volunteers.
AB  - Ten normotensive volunteers were imaged with FISP-3D (Fast Imaging Steady
      Precession) pulse sequences (a steady state gradient recalled echo, SS-GRE,
      technique) without and with modification by tilted, optimized non-saturating
      excitation (TONE) customized radio frequency (RF) pulses, for evaluation of the
      abdominal aorta--in particular the renal arteries. Maximum intensity projection
      (MIP) angiograms were constructed for each sequence in each volunteer; 15
      observers "blinded" to sequence type preferred the images generated from the TONE
      applied sequence. Analysis showed that this preference was significant.

PMID- 8298867
TI  - Human albumin base echocontrast agents--repeated use in animals may induce
      anaphylactic reactions.

PMID- 8298868
TI  - Prediction of birthweight by fetal ultrasound biometry.

PMID- 8298869
TI  - The indeterminate breast mass: assessment using contrast enhanced magnetic
      resonance imaging.
AB  - Magnetic resonance imaging of the breast was performed on 25 lesions in 24
      patients. These lesions were indeterminate on clinical and mammographic
      examination. The imaging findings were compared with pathological results in all
      cases. Conventional T1 and T2 spin echo images provided a certain diagnosis in
      only one case. The pattern of signal enhancement following gadolinium
      diethylamine triamine pentaacetic acid injection as demonstrated by a T1-weighted
      gradient recalled echo sequence permitted accurate diagnosis of four recurrent
      carcinomas and 19 cases of non-malignant disease (17 postoperative scars and two
      cases of benign breast disease). One false positive diagnosis of cancer was made
      in a case of fibroadenoma. Dynamic contrast enhanced magnetic resonance imaging
      may have a role in the assessment of the indeterminate breast mass.

PMID- 8298870
TI  - What is the nephrogram?
AB  - One of the oldest questions in radiology, "what is the nephrogram?", has been
      approached in a novel manner using dynamic bolus contrast enhanced computed
      tomography to monitor the arrival and distribution of contrast agent in the
      normal kidney. A modification of a mathematical technique first developed for
      applications in positron emission tomography has been used to analyse the data.
      It is concluded that the blood pool contribution to the nephrogram is greater in
      the first minutes after rapid bolus contrast injection than generally supposed
      and that the "immediate" nephrogram is a predominantly blood pool contrast
      phenomenon.

PMID- 8298871
TI  - The outcome of fetal ventriculomegaly.
AB  - Over a 5 year period 38 cases of fetal ventriculomegaly were diagnosed at Queen's
      Medical Centre, Nottingham. There were 12 cases of spina bifida and all patients
      opted for a termination of pregnancy. There were 15 cases of isolated
      ventriculomegaly comprising seven cases of aqueduct stenosis, four abnormalities
      of the corpus callosum, one cavum septum pellucidum cyst, one case of
      porencephaly and two cases of mild lateral ventricular dilatation. The fetuses in
      this group had a relatively good outcome with five babies showing normal
      development, three with mild development delay and one with moderate
      developmental delay. There was one stillbirth and five patients opted for a
      termination of pregnancy. Associated abnormalities were seen in seven cases and
      these carried a poor prognosis with one fetus stillborn, one neonatal death, and
      three patients opted for a termination of pregnancy. Two babies were liveborn,
      one has severe developmental delay and the other one is normal. The four
      remaining cases included two Dandy Walker syndrome, one brain tumour and one case
      of subdural haemorrhage. There were three terminations of pregnancy and one
      stillbirth in this group. The outcome of fetal ventriculomegaly depends on the
      presence of associated abnormalities which carry a poor prognosis. It also
      depends on the timing of the diagnosis as most patients will opt for a
      termination of pregnancy if the diagnosis is made before 24 weeks gestation. A
      review of the literature reveals that, excluding terminations, fetuses with
      isolated ventriculomegaly have an 80% chance of survival and a 50% chance of
      normal development.

PMID- 8298872
TI  - Identification of inappropriate radiological referrals with suspected gallstones:
      a prospective audit.
AB  - The objective of this study was to derive and test clinical scoring system in
      order to predict the presence of gallstones and to identify inappropriate
      referrals. The design of this scoring system comprised a prospective audit of all
      referrals with suspected gallstones and a prospective validation of the system on
      new patients. The subjects used in the study consisted of 300 inpatient,
      outpatient and general practitioner referrals to a radiology department with
      suspected gallstones during the period 1984-1986 (1st cohort) and 200 similar
      referrals from 1987 to 1988 (2nd cohort). The main outcome measures were
      gallstones as determined by oral cholecystogram and/or ultrasound of the
      gallbladder. 32.7% and 24.0% of referrals in the first and second cohorts,
      respectively, had gallstones. A scoring system to predict gallstones was derived
      on the first cohort based on age, Murphy's sign, duration and type of pain,
      presence or absence of flatulence, and source of referral. This scoring system
      discriminated well between those with and without stones in both cohorts. Low
      risk groups, comprising about 15% of the referrals in each cohort, were
      identified with a prevalence of gallstones of 4.5% (1st cohort) and 3.0% (2nd
      cohort). If these patients had not been referred the radiological workload would
      have dropped by 15%, with a very small reduction in diagnostic yield. We conclude
      that prior to radiological assessment it is possible, on the basis of source of
      referral and symptoms, to identify a group of patients with a low prevalence of
      gallstones. These cases, with a low diagnostic yield, contribute substantially to
      the workload of a radiological department.

PMID- 8298873
TI  - Phosphorus-31 metabolism of human breast--an in vivo magnetic resonance
      spectroscopic study at 1.5 Tesla.
AB  - We have studied the metabolism of compounds containing 31P in normal breast using
      magnetic resonance spectroscopy (MRS). Spectra were acquired from non-lactating
      pre-menopausal breast (n = 14 women), lactating breast (n = 8) and post
      menopausal breast (n = 8). The standard acquisition protocol used a 5.5 cm
      surface coil with the volunteer prone to minimize chest wall signal
      contamination. In pre-menopausal non-lactating women the phosphocreatine (PCr)
      peak area, expressed relative to the sum of all 31P peak areas, was negatively
      correlated with breast size (r = -0.56, p = 0.02) suggesting that much of the PCr
      signal originated from the chest wall. The phosphodiester (PDE) relative peak
      area was positively correlated with breast size (r = 0.71; p = 0.002). Spectra
      could be acquired at all phases of the menstrual cycle. In sequential
      examinations of five women not taking the oral contraceptive pill (OCP),
      phosphomonoester (PME) relative peak area was significantly lower on Week 2 than
      other weeks of the cycle (p = 0.03). Among pre-menopausal women no clear
      difference was apparent between the spectra from women taking the OCP and those
      not taking the OCP. Lactating breast had significantly higher PME relative peak
      area than non-lactating pre-menopausal breast (p = 0.02), probably reflecting the
      higher proportion of epithelial tissue in lactation; the lower PCr relative peak
      area in lactating breast (p = 0.05) is probably due to the greater size of the
      breast during lactation. Spectra were acquired from post-menopausal women but
      with a relatively low signal-to-noise ratio. The only significant difference
      between 31P relative peak areas of breast spectra acquired from pre- and post
      menopausal women was that less PCr was detected in the post-menopausal volunteers
      (p = 0.03), probably as a result of differences in breast size.

PMID- 8298874
TI  - A new method of quantification of the pulmonary regional distribution of aerosols
      using combined CT and SPECT and its application to nedocromil sodium administered
      by metered dose inhaler.
AB  - Aerosols of nedocromil sodium labelled with 99Tcm were delivered on 20 separate
      occasions to healthy male volunteers. Planar and single photon emission
      computerized tomography (SPECT) gamma scintigraphy were immediately performed to
      assess the pulmonary regional distribution of delivered aerosol. On a separate
      occasion volunteers were imaged using X-ray computed tomography (CT). Alignment
      of SPECT and CT images was performed using marked anatomical features and the
      anterior and lateral skin outlines. CT images provided data for attenuation
      correction and were used to define the anatomical lung volume. Central to
      peripheral (CP) ratios of deposited activity were calculated from volumes of
      interest in coronal and transverse sections of the right lung. These were
      compared with CP ratios obtained from planar images obtained immediately
      following aerosol inhalation. Volumetric CP ratio correlated significantly with
      immediate planar CP ratio (p < 0.001). Analysis of deposition in the whole right
      lung was performed by separating the SPECT lung data into a series of thin
      concentric shells centred on the entry of the right main bronchus. Measures were
      defined for describing the variation of deposition density and cumulative total
      deposition with distance from the lung centre. These showed significant
      correlation with planar CP ratio (p < 0.001). SPECT analysis using CT is
      consistent with planar measures of aerosol deposition but offers a more complete
      quantification of aerosol penetration and absolute deposited activity within the
      whole lung. It is a valuable new tool for aerosol analysis.

PMID- 8298875
TI  - Absorbed dose in the skin from beta emitters in medical and laboratory
      containers.
AB  - The International Commission on Radiation Protection have recently recommended an
      annual dose limit for the skin of radiation workers of 500 mSv at a depth of 20
      100 microns averaged over any 1 cm2 regardless of the area exposed. It has
      previously been shown by the authors that beta dose rates on the outer surfaces
      of typical laboratory containers (vials, test tubes) or on medical syringes can
      exceed 100 mSv h-1 for radionuclide concentrations of the order of 1 MBq g-1,
      depending on container diameter, wall thickness and material and the beta
      particle energy spectrum. Since the fingers are frequently in contact with such
      containers it is of some importance to extend these dose calculations to depths
      below the skin surface, taking into consideration the anatomy of skin on the
      fingers. Using an extension of a Monte Carlo method previously described, dose
      rates have been calculated for the clinically useful radionuclides 90Y, 32P,
      198Au, 153Sm and 131I. For polypropylene syringes the beta dose rates at a depth
      of 270 microns (a typical basal cell depth in the fingers) range from 77 to 135
      mGy h-1 per MBq g-1 for 90Y (maximum energy 2.27 MeV) and approximately zero to
      0.62 mGy h-1 per MBq g-1 for 131I (maximum energy 0.61 MeV). These results
      emphasize the importance of adequate finger protection when using high energy
      beta emitters and especially for clinicians who typically inject specific
      activities of the order of 100 MBq g-1 of 32P; in such cases annual permissible
      dose rates are exceeded in a matter of minutes. It is recommended that a minimum
      of 5 mm perspex finger protection be used for 90Y and 32P.

PMID- 8298876
TI  - Re-evaluation of a radiation protection cost benefit analysis study in
      brachytherapy.
AB  - Cost benefit analysis has been in use for many years as a method for making a
      comparison between the costs of radiation protection and the benefits of reduced
      radiation exposure. It is advocated by the International Commission on
      Radiological Protection (ICRP) and the National Radiological Protection Board
      (NRPB) has given more specific advice relating to the value of the man Sv to be
      used in the calculation of cost benefit. The purpose of this study is to
      investigate the changes in the NRPB advice over the last 10 years by correcting
      all figures for inflation and applying them to a particular radiation protection
      example. The example employed is a previously published case of the introduction
      of afterloading brachytherapy equipment at the Christie Hospital, Manchester. It
      has been shown that for this specific example the NRPB advice at one time led to
      a large cost benefit, at another time it led to a large cost deficit and later
      still it again gives a large cost benefit. Application of cost benefit analysis
      to decision making in radiation protection is therefore shown to be in need of
      further investigation and clarification before it can be used with confidence.

PMID- 8298877
TI  - Effect of overall time when radiotherapy includes teletherapy and brachytherapy:
      a mathematical model.
AB  - By expanding the linear quadratic equations to allow for the interval of time
      between teletherapy and brachytherapy in a model which assumes continual
      exponential tumour regression following teletherapy, the loge cell kill resulting
      from brachytherapy is found to depend on radiosensitivity, tumour regression rate
      (lambda) and tumour clonogen doubling time (Tp). When lambda is relatively small
      the precise timing of brachytherapy following teletherapy is shown to influence
      the tumour cure probabilities. The model predicts a reduction in tumour control
      if brachytherapy is delayed when lambda values are small and Tp values are short,
      but when Tp values are long, deferral of brachytherapy may be advantageous. By
      differential calculus the occurrence of a minimum value of log cell kill can be
      found. Application of these concepts may improve the results of clinical
      radiotherapy.

PMID- 8298878
TI  - Errors in dual-energy X-ray absorptiometry of the lumbar spine owing to fat
      distribution and soft tissue thickness during weight change.
AB  - It has previously been shown that the non-uniform distribution of fat leads to
      errors in the determination of spine bone mineral. If the fat error changes
      during alterations of weight, conclusions about bone mineral measurements might
      be compromised. To test this possibility, the distribution of adipose tissue was
      determined from X-ray CT scans taken for diagnostic purposes from patients whose
      weight had increased or decreased due to disease or treatment. For AP scanning
      the change in mean fat thickness over the vertebrae was similar to that in the
      background area, so that there was little change in fat error and therefore no
      misinterpretation of bone mineral measurements. Results were more variable for
      lateral scanning, sufficiently so as to question its validity in this context.
      The dependence of bone mineral measurements on the soft tissue thickness was
      investigated with three different makes of dual-energy X-ray absorptiometer and
      four spine models. A complex dependence was found, which varied with the bone
      mineral density, the thickness, the machine and the model. However, the magnitude
      of the dependence was not sufficient to falsify the conclusions about changes in
      bone mineral in two clinical studies in which patients had changed weight.

PMID- 8298879
TI  - Monte Carlo study of grid performance in diagnostic radiology: task dependent
      optimization for screen-film imaging.
AB  - An optimization of anti-scatter grid design using Monte Carlo techniques in
      diagnostic radiology is presented. The criterion for optimization was to find the
      combinations of the grid parameters (lead strip width, grid ratio and strip
      density) and tube potential which result in the lowest mean absorbed dose in the
      patient at fixed image contrast. The optimization was performed in three
      irradiation geometries, representing different scattering conditions (paediatric
      examinations, and two adult lumbar spine examinations) and was restricted to
      grids using fibre materials in covers and interspaces. Grid designs currently
      available were studied, as were designs which use thinner strips (< 30 microns)
      and higher grid ratios (> 18). It was found that grids with widely different
      strip densities (strips cm-1) and grid ratios can have good performance provided
      that they are used with appropriate strip width and tube potential. With
      increasing amounts of scatter, the optimal grid requires thicker strips and
      higher grid ratios. Increasing the strip density and using thinner strips and
      higher grid ratios are generally required. Grids with low strip density (25
      strips cm-1) were found to be less sensitive to alterations in strip width.
      Optimal grids for paediatric radiology require thinner strips (10-20 microns)
      than those in currently available grids. Grids on the market are best suited for
      examinations of the adult body in anteroposterior (AP) view. In the adult lateral
      view, representing the largest scattering volume, higher grid ratios (> 18) than
      those in existing grids would be optimal. Examples of good grid designs are given
      for each examination.

PMID- 8298880
TI  - Technical note: rapid measurement of left ventricular mass by spin echo magnetic
      resonance imaging.
AB  - Magnetic resonance (MR) imaging provides an accurate measurement of left
      ventricular mass but imaging time can be up to 45 min. We tested a more rapid
      multislice spin echo technique on 16 volunteers without evidence of heart
      disease. Multislice short axis spin echo images were acquired in up to three sets
      of five, clustered around end systole. Total imaging time was 15 min. Myocardial
      areas were summed and specific gravity was assumed. Comparison was made with
      multiple single acquisitions timed to end systole. There was good agreement
      between the two measurements of left ventricular mass. Mean (+/- standard
      deviation (sd), range) values were 212 g (+/- 41.71, 152 to 311) by the
      multislice method and 213 g (+/- 44.26, 155 to 317) by the single slice method.
      The mean difference (+/- sd of difference) between measurements was -1.72 +/-
      14.89 g (95% confidence interval for limits of agreement was +/- 14%). We have
      therefore established a more rapid and accurate method of measuring left
      ventricular mass.

PMID- 8298881
TI  - Case report: colour Doppler demonstration of pseudoaneurysms complicating
      pancreatic pseudocysts.
AB  - The great morbidity and mortality associated with pseudoaneurysms complicating
      pancreatic pseudocysts stress the need for their early detection. The authors
      report the use of colour Doppler sonography in the detection of pseudoaneurysms
      within pancreatic pseudocysts, emphasizing not only the value of this modality in
      the initial diagnosis, but also its value in monitoring the success of
      transcatheter embolization. Colour Doppler should be used systematically in the
      evaluation of pancreatic pseudocysts.

PMID- 8298882
TI  - Case report: extrathoracic herniation of the lung with a review of the
      literature.
AB  - A case of extrathoracic herniation of the lung is described together with the
      radiological findings in this condition including the role of computed tomography
      (CT) in its management. In addition a review of the literature is presented which
      outlines the incidence, classification and clinical features of lung herniae.
      Some reference is made to possible methods of treatment.

PMID- 8298883
TI  - Case report: a newborn case of chondrodysplasia punctata, tibia-metacarpal type.

PMID- 8298884
TI  - Use of bendrofluazide in the management of recurrent jejunal conduit syndrome.

PMID- 8298885
TI  - The image of the spermatic vein on a urethrogram after high velocity missile
      injury of the urethra in the presence of a varicocele.

PMID- 8298886
TI  - Trucut biopsy of the prostate: an unusual complication.

PMID- 8298887
TI  - Neoplastic Paneth cells in a mucinous adenocarcinoma of the bladder.

PMID- 8298888
TI  - Hypercalcaemia due to squamous cell carcinoma in a tuberculous kidney: case
      report and review of pathogenesis.

PMID- 8298889
TI  - Two simple cysts of the same testis.

PMID- 8298890
TI  - Prolapsed ureterocele: a rare vulval mass.

PMID- 8298891
TI  - Malakoplakia and carcinoma of the prostate.

PMID- 8298892
TI  - Wolfram's (DIDMOAD) syndrome.

PMID- 8298893
TI  - Analysis of factors associated with complications following renal transplant
      needle core biopsy.
AB  - OBJECTIVE: To determine factors associated with complications in patients
      undergoing renal transplant biopsy. PATIENTS AND METHODS: A total of 210
      consecutive renal transplant patients biopsied for acute graft dysfunction or as
      part of a long term surveillance programme. Biopsies were performed under
      ultrasound control at two centres (Nottingham City and Leicester General
      Hospitals). RESULTS: Seventeen patients developed macroscopic haematuria
      following biopsy (8%). There were no graft losses. In cases where at least one
      biopsy core contained only renal medullary tissue, there was a significantly
      higher risk of a post-biopsy bleed (P < 0.001). CONCLUSION: This study
      demonstrates that even with careful ultrasound guidance, renal transplant biopsy
      has an important complication rate. Every effort must be made to obtain very
      superficial biopsies which consist largely or exclusively of renal cortex.

PMID- 8298894
TI  - Hydatid disease of the kidney.
AB  - OBJECTIVE: To define the clinical manifestations of echinococcal involvement of
      the urinary tract and to propose guidelines for treatment. PATIENTS AND METHODS:
      A positive diagnosis of hydatid disease was made in seven patients and in all of
      these the cyst was located in the kidney only. The patients included four males
      and three females whose ages ranged from 6 to 56 years (mean 33.3). RESULTS:
      Surgical treatment involved total nephrectomy in six patients and partial
      nephrectomy in one patient. There was no operative or post-operative mortality
      and all patients were cured of the disease. CONCLUSION: Despite its rarity,
      hydatid disease should be considered in the differential diagnosis of space
      occupying lesions of the urinary tract.

PMID- 8298895
TI  - Combination of lymphokine-activated killer cells and interleukin-2 in treating
      metastatic renal cell carcinoma.
AB  - OBJECTIVE: To study the properties of lymphokine-activated killer (LAK) cells and
      the effect of immunotherapy with a combination of autologous LAK cells and
      interleukin-2 (IL-2) [LAK therapy] in 10 patients with metastatic renal cell
      carcinoma (RCC). MATERIALS AND METHODS: The LAK cells were generated from
      peripheral blood lymphocytes (PBL) by incubation in a serum-free medium (AIM-V)
      supplemented with IL-2 for 4 days and killer cells were administered
      intravenously twice a week. The LAK cells showed cytotoxicity against allogenic
      RCC cell lines and augmented NK and LAK activities. Their phenotypes were CD25+,
      HLA-DR+, CD3+, and CD16+. Furthermore, LAK cells released IFN-gamma, IL-1 beta,
      and TNF-alpha. The total number of LAK cells administered ranged from 3.8 x 10(9)
      to 52.6 x 10(9) cells and the total amount of IL-2 ranged from 150 x 10(5) to 900
      x 10(5) U. The effect on pulmonary metastasis in response to LAK therapy was
      studied. RESULTS: The outcome was complete response (1), partial response (1),
      minor response (2), no change (4) and disease progression (2). Toxic effects were
      transient and no serious side-effects occurred. Evaluation of host immune
      parameters indicated that a clinical response was expected in patients with
      increasing proportions of CD16+, CD25+, CD57+, HLA-DR+ and CD3+DR+ cells among
      PBL and with augmentation of NK and LAK activities. Brain metastases were
      detected in three patients during or after treatment. CONCLUSION: LAK therapy
      appears to be effective in treating some patients with RCC and pulmonary
      metastasis. The potential for inducing brain metastasis, however, should be taken
      into account.

PMID- 8298896
TI  - The unstable bladder: towards a common mechanism.

PMID- 8298897
TI  - Ureteric retrieval net: comparison with stone extraction by Dormia baskets in an
      in vitro porcine model.
AB  - OBJECTIVE: To develop a ureteric retrieval net with advantages over existing
      stone retrieval methods. MATERIALS AND METHODS: In vitro experimental trials
      comparing the ureteric retrieval net with Dormia baskets were performed with
      porcine ureters and artificial calculi placed in a proximal or distal position.
      RESULTS: For removing a single, large stone (9 x 6 x 5 mm) the net was slightly
      better than baskets (100% versus 90%) and it was significantly (P < 0.001) more
      effective for removing multiple small stones (2 x 2 x 3 mm to 5 x 4 x 3 mm) in
      one pass (76% versus 40% with three distal stones; 73% versus 13% with three
      proximal stones; and 53% versus 3% with six proximal stones). CONCLUSION: This
      newly developed ureteric retrieval net has a compact design, resulting in minimal
      resistance during retraction. Its smooth hydrophilic outer surface enhances
      scooping properties against the luminal wall. The mesh is similar to that in
      nylon stockings--porous enough to allow flow, yet small enough to capture
      fragments. It can capture numerous small fragments with one scoop, but can easily
      disengage them if extraction is not possible. The loop encompasses the entire
      lumen with the 'pusher' offset to a side wall, allowing maximal space and
      visualization, and the device can dilate the ureter to facilitate extraction.
      Clinical studies are in progress to evaluate the full potential of this new
      device.

PMID- 8298898
TI  - Retrograde manipulation for proximal ureteric stones before extracorporeal
      shockwave lithotripsy: technique, observations and results.
AB  - OBJECTIVE: To determine the factors affecting the success of retrograde
      manipulation (RM) of upper ureteric stones. PATIENTS AND METHODS: A total of 601
      patients with upper ureteric calculi underwent attempted RM. In 216 patients, RM
      was performed irrespective of the respiratory phase, stone characteristics and
      ureteric anatomy (group 1). In the remaining 385 patients RM was performed at the
      height of expiration (group 2). Patients with large or impacted stones, ureters
      with a fusiform or funnel shape appearance on urography and grade IV
      hydronephrosis were not included in group 2. RESULTS: The success rate was
      significantly greater in group 2. The rates of fever and perforation in groups 1
      and 2 were 6.9/2.3% and 3.2/0.2% respectively. The incidence of residual
      fragments was also less in group 2. CONCLUSION: RM at the height of expiration is
      associated with a higher success rate and lower complication rate.

PMID- 8298899
TI  - Transverse colon conduit urinary diversion in patients treated with very high
      dose pelvic irradiation.
AB  - OBJECTIVE: To study the results of transverse colon conduit urinary diversion in
      patients receiving very high dose pelvic irradiation (> or = 65 Gy). PATIENTS AND
      METHODS: Records were reviewed for 30 such patients who underwent transverse
      colon conduit as a primary form of urinary diversion between January 1986 and
      June 1992. Most of the conduits were constructed using refluxing ureterocolic
      anastomoses with stents. RESULTS: There was no operative mortality. Although the
      procedure was associated with a complication rate of 37% and a re-operation rate
      of 20%, there were no bowel or urinary anastomotic leaks. The operation could be
      safely performed on patients with renal failure, with 83% of such patients
      showing normal or improved serum creatinine levels post-operatively. CONCLUSION:
      The advantages of transverse colon conduit urinary diversion are the use of non
      irradiated bowel and ureters for diversion. We recommend it as a primary form of
      urinary diversion in these high risk cases.

PMID- 8298900
TI  - The Mitrofanoff principle for urethral failure.
AB  - OBJECTIVE: To assess the outcome of surgery for urethral failure. PATIENTS AND
      METHODS: Patients undergoing lower urinary tract reconstruction are recorded
      prospectively by protocol. Thirty-four are presented whose urethra had failed as
      a conduit; in 23 the urethra was incontinent and in 11 it was spastic causing
      chronic retention. The incontinent patients had failed a variety of
      reconstructions, in five including insertion of an artificial sphincter. Those
      with chronic retention were unable to self-catheterize the urethra. RESULTS: A
      continent supra-public diversion using the Mitrofanoff principle was performed.
      In two patients a new technique was used in which a detrusor tube formed the
      continent conduit. Ninety-four per cent of patients were continent. Two patients
      voided to completion, the remainder emptied by self-catheterization. Five minor
      revisions were required to allow easy catheterization. There was one death. The
      complication rate was 17%. CONCLUSION: This type of reconstruction is preferable
      to the formation of an ileal conduit in this difficult group of patients.

PMID- 8298901
TI  - Transrectal ultrasonography to assess local extent of prostatic cancer before
      radical prostatectomy.
AB  - OBJECTIVE: To evaluate transrectal ultrasonography (TRUS) with a 7 mHz rotating
      probe as a staging procedure in 33 patients with localized prostatic carcinoma.
      PATIENTS AND METHODS: The ultrasound scans were compared to histopathological
      whole-mount step sections of the surgical specimens. Twenty-five of the patients
      had tumours with pathological stage T3 (pT3) and eight had tumours with stage pT2
      giving a prevalence of extracapsular growth of 0.76. RESULTS: The overall
      sensitivity, specificity, positive and negative predictive values for detection
      of extracapsular tumour growth by TRUS of prostatic cancer were found to be 0.68,
      0.63, 0.85 and 0.38, respectively. Six tumours showed solely microscopic foci of
      extracapsular tumour growth. CONCLUSION: This technique gives a high percentage
      of both understaging (32%) and overstaging (37%) and therefore TRUS is an
      unreliable tool in the staging protocol prior to radical prostatectomy.

PMID- 8298902
TI  - Role of penile vascular injury in erectile dysfunction after radical
      prostatectomy.
AB  - OBJECTIVE: To investigate the cause of erectile dysfunction after nerve-sparing
      radical prostatectomy for clinically localized adenocarcinoma of the prostate
      (stage A or B). PATIENTS AND METHODS: Erectile function was evaluated in 20
      patients, mean age 65 years (range 44-74), both pre-operatively and 1 year after
      surgery by intracavernosal injection of a vasoactive agent (papaverine
      hydrochloride or prostaglandin E1) and pulsed Doppler ultrasonography. The degree
      of erection, the size of the cavernosal artery and penile arterial blood flow
      velocity were assessed. RESULTS: Results revealed that the decreased response to
      intracavernosal injection of a vasoactive agent was associated with a significant
      reduction in both the diameter and velocity of blood flow within cavernosal
      arteries in 40% of patients after surgery. The pathological stage of the tumour
      did not correlate with the degree of vascular injury. CONCLUSION: We conclude
      that post-prostatectomy impotence is multifactorial but vascular injury plays a
      substantial role.

PMID- 8298903
TI  - Xanthogranulomatous pyelonephritis in childhood: pre-operative diagnosis is
      possible.
AB  - OBJECTIVE: To diagnose xanthogranulomatous pyelonephritis (XGP) in childhood pre
      operatively. PATIENTS AND METHODS: Eleven cases of XGP presenting to Birmingham
      Children's Hospital over a 10-year-period are reported. Nine (82%) were diagnosed
      preoperatively on the clinical and radiological findings. RESULTS: The
      characteristic clinical findings were urinary tract infection (9 cases), palpable
      renal mass (8 cases) and anaemia (8 cases). The most common radiological findings
      were enlarged kidney (9 cases), renal calculi (7 cases) and non-functioning
      kidney (6 cases). Renal ultrasound typically demonstrated a central echoic area
      (6 cases) and multiple hypoechoic areas in the parenchyma (7 cases). A computed
      tomography (CT) scan was performed in three cases. This showed characteristic
      multiple, low attenuation, unenhanced areas within the parenchyma with extension
      of the inflammatory process into peri-nephric fat (two cases). Ten cases (91%)
      were of the diffuse type. There was extension into the peri-nephric fat in eight
      cases (73%). Three cases (27%) were associated with congenital urological
      abnormalities. Nephrectomy was performed in 10 cases and a partial nephrectomy in
      one. CONCLUSION: XGP is uncommon in childhood but should always be considered in
      the differential diagnosis of renal masses, especially in the presence of
      anaemia. Nephrectomy usually results in a permanent cure.

PMID- 8298904
TI  - Complications and length of hospital stay following stented and unstented
      paediatric pyeloplasties.
AB  - OBJECTIVES: To ascertain the necessity for the use of nephrostomies and ureteric
      stents after paediatric pyeloplasties. PATIENTS AND METHODS: Seventy children
      with a pelvi-ureteric junction obstruction underwent a dismembered pyeloplasty
      between March 1983 and March 1991 at The Bristol Royal Hospital for Sick
      Children. A nephrostomy and stent were not used routinely except for the first
      few months of the survey. Indications for their use were: surgery on a single
      kidney, an inflamed renal pelvis or a revision pyeloplasty. Urinary catheters
      were only used for those patients with proven or suspected vesicoureteric reflux.
      RESULTS: Thirteen patients had a nephrostomy and stent inserted (Group 1) of whom
      three patients (23%) developed complications. Fifty-seven patients had only a
      wound drain inserted (Group 2) of whom nine (16%) developed complications. The
      hospital stay of 12.1 days for patients in Group 1 was significantly longer than
      the 5.4 days for Group 2 (P value < 0.05). Long-term radiological and/or radio
      isotopic follow-up showed improvement in function and/or drainage in 95% of both
      groups. CONCLUSIONS: These findings support the concept that paediatric
      pyeloplasties can be safely performed at any age without the insertion of a
      nephrostomy tube or stent and that hospital stay is therefore significantly
      reduced.

PMID- 8298905
TI  - Admiral Rodney's urological indisposition: its impact on the American revolution.

PMID- 8298906
TI  - Congenital urethral obstruction: Cobb's collar or prolapsed congenital
      obstructive posterior urethral membrane (COPUM).
AB  - OBJECTIVE: To determine whether there are two distinct types of congenital
      obstruction of the proximal urethra. PATIENTS AND METHODS: Three boys with a
      congenital bulbar urethral narrowing (Cobb's collar) were examined. Recent papers
      on congenital obstructive posterior urethral membrane (COPUM) were reviewed.
      RESULTS: The more proximal lesion is a membranous obstruction which is able to
      prolapse as far as the bulbar urethra, but has paramedian folds that attach along
      the posterior wall of the urethra to the verumontanum, and is due to persistence
      of an embryological attachment between the distal verumontanum and the anterior
      wall of the posterior urethra. The more distal narrowing is not always
      obstructive and is primarily a bulbar urethral membrane, is independent of the
      verumontanum and external sphincter, and may represent a persistence of part of
      the urogenital membrane. CONCLUSIONS: There are two distinct types of congenital
      obstruction of the proximal urethra, with the association to the verumontanum
      being the distinguishing feature.

PMID- 8298907
TI  - Fracture of the penis causing a corporo-urethral fistula.

PMID- 8298908
TI  - Painful shrinking testis and Pagetoid spread of germ cell neoplasia in the rete
      testis.

PMID- 8298909
TI  - Primary amyloidosis of the renal pelvis and upper ureter.

PMID- 8298910
TI  - Acute pancreatitis: the value of life.

PMID- 8298911
TI  - 'Damage control' in trauma surgery.

PMID- 8298912
TI  - Role of the leucocyte in the pathogenesis of vascular disease.
AB  - The leucocyte plays a key role in the local and systemic tissue injury that
      results from peripheral arterial disease and chronic venous insufficiency.
      Despite the apparent dissimilarities between limb ischaemia and chronic venous
      ulceration, in both diseases macrovascular abnormalities lead to microvascular
      leucocyte trapping and activation. Activated leucocytes adhere to and damage
      adjacent endothelium by expressing adhesion molecules and releasing harmful
      moieties such as proteases and free radicals. Subsequent loss of endothelial
      integrity and the migration of activated leucocytes outwith the circulation leads
      to destruction of surrounding tissue. Leucocytes and their products are also
      involved in the systemic manifestations of ischaemia such as multiple organ
      failure and coagulopathy. An overview of leucocyte biology as it pertains to
      peripheral arterial and venous disease is presented. The opportunities for novel
      therapeutic interventions based on a better understanding of this biology are
      also discussed.

PMID- 8298913
TI  - Cocaine 'body packers'.
AB  - Intracorporeal drug smuggling, particularly of cocaine, is increasing. The so
      called 'body packers' present a difficult clinical problem, particularly as no
      coherent management policy has been formulated. The various methods of diagnosis
      and the treatment options available are presented and discussed.

PMID- 8298914
TI  - Factors influencing the hyperaemic response after carotid endarterectomy.
AB  - Transcranial Doppler ultrasonography was used to evaluate serially the changes in
      middle cerebral artery blood flow velocity (MCAV) in 37 consecutive patients
      during the first 72 h after carotid endarterectomy to identify factors that may
      predispose towards postoperative hyperaemia. Within 6 h of endarterectomy, median
      MCAV in the operated hemisphere was 48 per cent (95 per cent confidence interval
      37-60 per cent) above that on admission and remained 27 per cent (95 per cent
      confidence interval 19-37 per cent) higher at 72 h. There was a similar, but less
      marked, increase in MCAV in the contralateral middle cerebral artery during the
      same time period. There was no association between the postoperative increase in
      MCAV and clinical presentation, admission MCAV, the presence or absence of a
      residual neurological deficit or infarction on computed tomography before
      operation, carotid clamp time, shunt usage, internal carotid artery stump
      pressure or MCAV during clamping. The greatest increase in MCAV was observed in
      patients with internal carotid artery stenosis > or = 50 per cent and, more
      particularly, in those with preoperative evidence of impaired cerebrovascular
      reserve. In the latter patients, MCAV was 100 per cent above the admission level
      within 12 h of operation and was still 50 per cent raised at 72 h.

PMID- 8298915
TI  - Spontaneous staphylococcal peritonitis in an otherwise healthy young man.

PMID- 8298916
TI  - Randomized controlled trial of patch angioplasty for carotid endarterectomy. The
      Joint Vascular Research Group.
AB  - A randomized controlled trial was performed to evaluate patch angioplasty for
      patients undergoing carotid endarterectomy. There were 213 patient episodes
      affecting 148 men and 65 women, with 109 allocated to patch angioplasty.
      Following surgery six patients suffered transient ischaemic attacks but these did
      not delay discharge from hospital. Six individuals (four patched operations, two
      not patched) required re-exploration for postoperative haemorrhage and eight (two
      patched procedures, six not) had potentially serious neurological problems after
      operation. Of these eight patients, four (none receiving patch angioplasty)
      underwent re-exploration and in each case a clot was removed and a patch
      inserted; three of the four made a good long-term recovery. The other four
      patients suffered completed strokes from which one died. Two further patients
      (one patched procedure, one not) died after operation from myocardial events,
      giving an overall 30-day stroke or mortality rate of 2.8 per cent. Objective
      follow-up assessment with duplex scanning at 1 year was completed by 94.8 per
      cent of patients; significantly more vessel restenoses and occlusions were
      observed in those not receiving patches (P < 0.01). Patch angioplasty reduces the
      number of immediate postoperative complications, and significantly lowers vessel
      restenosis and occlusion rates at 1 year after operation.

PMID- 8298917
TI  - Popliteal aneurysm: morphology and management.
AB  - Since January 1988, 32 patients have presented with 44 popliteal aneurysms (22
      thrombosed, 22 non-thrombosed). Patients with thrombosed aneurysms were older
      (median age 72 versus 66 years), and more likely to have bilateral lesions (P <
      0.02) and serious associated cardiovascular disease (P < 0.02). Nineteen
      aneurysms thrombosed acutely; 12 were treated with intra-arterial thrombolysis,
      which was at least partially successful in seven. All 12 were subsequently
      bypassed, as were the other seven which were associated with such severe
      ischaemia that they required urgent operation. One patient died and two others
      required major amputation. Other complications included foot-drop (two patients),
      renal failure (one) and wound infection (two). Two grafts thrombosed and required
      re-exploration. Elective bypass was carried out in 11 patients without acutely
      thrombosed aneurysms; there were no significant postoperative problems.
      Distortion within the aneurysm (P < 0.01), large size (P < 0.01) and distortion
      of the popliteal artery above or below the lesion (P < 0.02) were all associated
      with thrombosis. Stenosis within the aneurysm was more likely in patients with
      multiple lesions (P < 0.01) and distortion with larger aneurysms (P < 0.01).
      After correcting for distortion, none of the other variables was independently
      significant. The combination of distortion and diameter > 3 cm was present in 13
      of 15 thrombosed aneurysms. Morbidity is high following acute thrombosis of
      popliteal aneurysm. Distortion of the aneurysm appears to be a more sensitive
      predictor of thrombosis than size alone. The combination of distortion with a
      diameter > 3 cm may help to define popliteal aneurysms that should be bypassed
      electively.

PMID- 8298918
TI  - Physical examination and selective conservative management in patients with
      penetrating injuries of the neck.
AB  - This prospective study of 335 patients with penetrating injuries of the neck
      examined the decision whether to operate or observe according to a protocol based
      mainly on physical examination. Emergency angiography was performed in only three
      patients. Sixty-six patients (20 per cent) were subjected to emergency operation
      because of signs and symptoms suggestive of significant injury (60 patients) or
      because of positive investigations (six). The remaining 269 patients (80 per
      cent) were selected for non-operative management. Two of these patients (0.7 per
      cent) required elective operation during the initial hospital stay. No deaths
      occurred in patients treated conservatively. Some 192 (72 per cent) of observed
      patients were available for early follow-up and 111 (42 per cent) for late follow
      up. No significant complications were found. Physical examination is a reliable
      method for detecting significant injuries following penetrating neck trauma.
      Emergency angiography is rarely necessary.

PMID- 8298919
TI  - Short myotomy for vigorous achalasia.
AB  - Vigorous achalasia has been considered an indication for surgery, in which a
      thoracic approach is recommended for extending the myotomy along the whole of the
      oesophageal body to the point where manometry shows high-amplitude waves.
      Clinical results and postoperative manometric findings in 16 patients with
      vigorous achalasia undergoing abdominal surgery with myotomy limited to the lower
      oesophageal sphincter (LOS) were analysed to assess whether extended myotomy is
      necessary in surgery for this form of achalasia. The clinical results were
      excellent or good in all cases. Surgery induced a significant decrease (P < 0.01)
      in the diameter of the oesophagus as determined radiologically. The most
      significant postoperative manometric changes were a decrease in the resting
      pressure of the LOS and oesophageal body, a lowering of wave amplitude at all
      levels of the oesophagus, and a reduction in the proportion of repetitive waves.
      The results suggest that vigorous achalasia can be treated surgically in the same
      way as classical achalasia and question, at least from a therapeutic viewpoint,
      the use of the term vigorous achalasia.

PMID- 8298920
TI  - Granulocyte-macrophage colony-stimulating factor inhibits tumour growth.
AB  - The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on murine
      antitumour responses was examined. Sixty mice received Lewis lung carcinoma
      implants and were then randomized to receive GM-CSF 1 microgram/day, GM-CSF 0.5
      microgram/day or saline for 10 days and studied with regard to tumour volume,
      carcass weight and food intake. Macrophage antitumour mechanisms including oxygen
      free radical production and nitric oxide release were studied in peritoneal
      macrophages after co-culture with GM-CSF in vitro and in vivo. GM-CSF 1
      microgram/day decreased tumour growth after 5 days (mean(s.e.m.) 0.62(0.14)
      versus 1.24(0.19) cm3, P = 0.017). GM-CSF upregulated macrophage antitumour
      mechanisms by enhancing the in vivo production of superoxide radicals
      (mean(s.e.m.) 0.69(0.06) versus 0.45(0.10) nmol, P < 0.05) and nitric oxide
      (mean(s.e.m.) 48(3) versus 24(4) mumol, P < 0.01). GM-CSF functions through the
      enhancement of macrophage tumoricidal activity, suggesting a therapeutic
      potential for this cytokine in the tumour-bearing host.

PMID- 8298921
TI  - Role of surgery and chemotherapy for peripheral lymph node tuberculosis.
AB  - A total of 105 patients with peripheral lymph node tuberculosis were treated by
      either surgical excision and chemotherapy or chemotherapy alone. The cervical
      nodes were affected in 98 patients, axillary nodes in four and inguinal nodes in
      three. Biopsy of the lymph nodes confirmed the diagnosis in all cases. Thirty
      five patients who had sinus, ulcer or abscess underwent excision of the lymph
      nodes with drainage of the abscess, or resection of the sinus or ulcer. The
      remaining 70 patients received only chemotherapy. Chemotherapy in all patients
      consisted of isoniazid and ethambutol for 18 months. Of the 35 patients treated
      with surgery and chemotherapy, two had gaping wounds, one infection and one
      cellulitis of the face and neck. After 3 months, one patient had recurrence of
      the lymph node mass and one recurrence of a sinus; these were excised. Of the 70
      patients treated only with chemotherapy, 13 were lost to follow-up. Four had non
      healing wounds at the biopsy site, six wound infection and two sinus formation.
      Five of these patients had persistent lymph node masses, which were excised after
      3 months. The remaining 52 patients had no recurrence.

PMID- 8298922
TI  - Prognostic value of DNA ploidy in primary gastric leiomyosarcoma.
AB  - The prognostic value of DNA ploidy was evaluated in 25 patients with primary
      gastric leiomyosarcoma, using paraffin-embedded archival specimens analysed by
      DNA flow cytometry. Ploidy patterns were diploid in ten tumours and non-diploid
      in 15. They did not correlate with clinicopathological features of the lesions
      such as tumour size and grade or mitotic index. A non-diploid pattern was
      associated with a significantly reduced patient survival rate (P < 0.05), as was
      higher tumour grade (P < 0.01). Neither tumour size nor mitotic index correlated
      with patient survival.

PMID- 8298923
TI  - Raised serum CA125 level in leiomyoma and leiomyosarcoma of gastrointestinal
      origin.

PMID- 8298924
TI  - Laparoscopic omental patch repair of perforated duodenal ulcer with an automated
      stapler.

PMID- 8298925
TI  - Reliability of clinical judgement in evaluation of the nutritional status of
      surgical patients.
AB  - The ability of surgeons to make a reproducible and reliable evaluation of the
      nutritional status of patients was assessed. Three independent observers assigned
      64 patients to one of four nutritional states--normal nourishment, and mild,
      moderate and severe malnutrition--using a questionnaire and clinical examination.
      Interobserver variability was analysed using the kappa statistic and reliability
      by assessing the correlation between the assigned class and total serum protein,
      haemoglobin, albumin, transferrin and cholesterol levels, weight loss and the
      results of immunological skin tests. Concordance was observed in 49 of the 64
      judgements (77 per cent) and partial agreement in the remainder (kappa = 0.74, P
      < 0.001). Clinical judgement correlated significantly with albumin, transferrin
      and cholesterol levels and weight loss (R2 = 0.73, P < 0.001). Surgeons are able
      to assess nutritional status using clinical judgement.

PMID- 8298926
TI  - Repeat hepatectomy for cancer.
AB  - In a series of 279 hepatectomies performed for cancer between June 1984 and March
      1992, 46 were repeat operations, for metastases in 41 patients. The primary
      tumour was in the colon and rectum (28 patients), APUDoma (five) and
      miscellaneous (eight). Repeat hepatectomies were performed in 26 per cent of
      patients who had recurrence after the first liver resection and in 40 per cent of
      those who had liver recurrence. An unsuspected extrahepatic recurrence was
      discovered and resected in eight instances and in two other cases a known
      extrahepatic recurrence was resected during the second hepatectomy. The hospital
      mortality rate was 2 per cent (one patient); the death was from nosocomial
      pneumonia. The total morbidity rate including minor complications was 32 per
      cent, with a higher frequency of haemorrhagic problems after secondary liver
      resection (12 per cent) than after primary hepatectomy (5 per cent). The rate of
      postoperative complications after repeat hepatectomy was related significantly to
      operative blood loss greater than 1500 ml (P = 0.04). The technical problems of
      repeat hepatectomy were: (1) re-exposure of the liver, considered to be difficult
      in 67 per cent of second liver resections and 80 per cent of third procedures;
      (2) the liver parenchyma, which often had histological modifications between
      first and second resections and was more difficult to 'work' as shown by the mean
      duration of clamping of the hepatic pedicle (54 min for secondary versus 36 min
      for primary liver resection); and (3) modification of the intraparenchymal
      vasculobiliary anatomy following liver regeneration after major hepatectomy.
      Intraoperative ultrasonography was of great benefit. Rates of crude and
      recurrence-free survival were relatively encouraging at 47 and 33 per cent 3
      years after the second liver resection for the whole group. These values were
      lower for colorectal cancer (37 and 21 per cent 3 years after the second
      hepatectomy). These figures do not, however, convey the complete picture of the
      outcome for these patients. During the same follow-up period, 143 recurrences
      were detected and a mean of 2.9 resections per patient were performed. The
      indications for repeat hepatectomy are still to be clarified, although the
      surgical technique is safe.

PMID- 8298927
TI  - Haemostasis after partial hepatectomy using argon beam coagulation.
AB  - The argon beam coagulator is a new device for haemostasis during and after
      surgery on parenchymatous organs. No data are available on its efficacy and
      tissue effect following hepatic resection. Blood loss, the time needed to achieve
      adequate haemostasis and histological findings after liver resection were
      assessed in 12 pigs using argon beam coagulation or suture ligation only, the
      mattress suture technique and tissue glue application. The treatment was randomly
      assigned to each of the four liver lobes in each pig. Median blood loss following
      argon beam coagulation was 13 (range 2-47) ml and after simple suture ligation 55
      (range 2-260) ml (P < 0.02). The median time needed for adequate haemostasis
      following argon beam coagulation was 3 (range 2-7) min versus 14 (range 2-48) min
      in the control group (P < 0.005). There was no difference between argon beam
      coagulation and tissue glue, which were both superior to the use of mattress
      sutures. Argon beam coagulation resulted in less tissue damage than tissue glue
      or mattress suturing. The argon beam coagulator is an efficient device for
      achieving haemostasis following partial hepatectomy in the pig. It causes only a
      moderate tissue reaction.

PMID- 8298928
TI  - Prolonged normothermic ischaemia of human cirrhotic liver during hepatectomy: a
      preliminary report.
AB  - To evaluate the tolerance of the cirrhotic liver to extended warm ischaemia, 47
      patients with cirrhosis who underwent liver resection over a 4-year period were
      studied retrospectively. Three groups of patients were identified. In group 1 (14
      patients) liver resection was performed under conditions of portal triad
      occlusion ranging from 50 to 75 (mean 57.1) min. Group 2 (12 patients) was
      treated with portal occlusion for a period ranging from 30 to 42 (mean 33.1) min.
      Group 3 comprised 21 patients who underwent hepatectomy using conventional
      techniques. Mean blood loss was significantly reduced by portal triad occlusion
      (819 ml in group 1, 523 ml in group 2) compared with the conventional technique
      (1652 ml in group 3) (P < 0.05, group 1 versus group 3; P < 0.01, group 2 versus
      group 3). Hospital death occurred in three of the 21 patients in group 3 but in
      no patient who underwent portal triad occlusion. The morbidity rate was lower in
      the two occlusion groups (four of 26 patients) than in group 3 (six of 21).
      Bilirubin metabolism was substantially better after surgery in the occlusion
      groups (P < 0.05, groups 1 and 2 versus group 3 at day 14). Although the serum
      levels of transaminases were significantly raised until day 3 in patients
      undergoing long-term occlusion, the cirrhotic liver withstood the ischaemia
      reperfusion insult, as assessed by changes in hepatic microcirculation, lipid
      peroxidation and the morphology of hepatic sinusoids. It is concluded that
      prolonged ischaemia during liver resection can be sustained in patients with
      cirrhosis and without high-risk factors.

PMID- 8298929
TI  - Laparoscopic ultrasonography for hepatobiliary and pancreatic malignancy.
AB  - Despite the advances made since the introduction of ultrasonography, computed
      tomography and magnetic resonance imaging, a wide discrepancy may occur between
      preoperative and peroperative staging of gastrointestinal malignancy with liver
      and peritoneal metastases. Diagnostic laparoscopy performed immediately before a
      planned laparotomy can provide valuable information for the accurate assessment
      and appropriate management of some forms of gastrointestinal malignancy,
      especially that of the liver and pancreas. For evaluation of small liver and
      retroperitoneal malignancies, intraoperative ultrasonography performed by
      laparotomy is of proven value. It is now technically possible to perform
      ultrasonography through a laparoscopic cannula using high-resolution
      ultrasonographic transducers. This combination of laparoscopy and ultrasonography
      was studied in 25 patients with established liver lesions, carcinoma of the
      gallbladder or pancreatic cancer. Additional information leading to a change in
      surgical approach was obtained in 20 patients. Laparoscopic ultrasonography,
      although still in a preliminary phase of development, is a simple and reliable
      technique that will contribute to more accurate staging of intra-abdominal
      malignancy.

PMID- 8298930
TI  - Pancreatic necrosis: assessment of outcome related to quality of life and cost of
      management.
AB  - Ten patients with necrotizing pancreatitis admitted consecutively between August
      1990 and August 1991 were studied. They comprised eight men and two women of
      median age 63 (range 29-73) years. One patient died. The median length of
      hospital stay was 74 (range 40-150) days. The median number of operations and
      endoscopic procedures performed per patient was 4 (range 2-7). Investigations
      performed included multiple bacteriological, radiological, haematological and
      biochemical tests. The mean cost of management was 18,441 pounds (range 9,296
      pounds-33,796 pounds), of which hospitalization accounted for 65 per cent,
      operations and endoscopic procedures 20 per cent and investigations 16 per cent.
      Cost-utility analysis demonstrated a mean benefit per patient of 8.55 quality
      adjusted life years gained at a cost of 2,157 pounds each. The management of
      pancreatic necrosis is expensive but justified by the excellent outcome in terms
      of quality of life.

PMID- 8298931
TI  - Good long-term results in patients surviving severe acute pancreatitis.
AB  - Thirty-seven patients treated for severe acute pancreatitis were investigated a
      mean of 6.2 years after the attack; 30 were found to be in good condition and 24
      were working normally. Two-thirds of previously heavy drinkers had either reduced
      their intake considerably or become abstainers. The main complication observed on
      follow-up was diabetes mellitus, which affected 20 patients and required insulin
      treatment in nine. Of the remaining patients, four were taking oral antidiabetic
      agents and seven were on a strict diabetic diet. Before severe acute pancreatitis
      none had been diabetic. All patients who underwent resection of the pancreas
      developed diabetes. In 21 of 24 patients with over or imminent diabetes,
      pancreatitis had been primarily alcoholic in origin. Polyneuropathy, as diagnosed
      by clinical signs and/or neurophysiological tests, was observed in six patients,
      all of them heavy drinkers. It is concluded that patients with severe acute
      pancreatitis have a high chance of returning to normal activity and productive
      work. These results serve to encourage all those involved to persist with the
      exacting work involved in treating such patients.

PMID- 8298932
TI  - Early discharge after operation.
AB  - To assess the feasibility and advantages of short-stay surgery in India, a policy
      of early discharge was adopted for 386 patients undergoing various major and
      minor operations. The mean postoperative and total hospital stays of patients
      admitted for minor surgery were 1.9 and 3.7 days respectively; the corresponding
      figures for age- and sex-matched historical controls were 7.4 and 11.3 days. The
      mean postoperative and total stays of patients who had undergone major surgery
      were 4.1 and 8.0 days respectively; the corresponding control values were 8.9 and
      12.5 days. The use of absorbable subcuticular skin sutures helped to shorten
      postoperative hospital stay and avoided an extra follow-up visit. The overall
      complication rate in the study group was 9.6 per cent and in historical controls
      13.4 per cent (P > 0.05). A total of 2357 hospital bed-days were saved during the
      study and 95.6 per cent of patients approved of short-stay surgery.

PMID- 8298933
TI  - Bile duct injury and bile leakage in laparoscopic cholecystectomy.
AB  - Between January 1991 and July 1992, 350 laparoscopic cholecystectomies were
      performed. There were six biliary complications (1.7 per cent): common bile duct
      (CBD) injury (one patient), delayed CBD necrosis (one), immediate postoperative
      bile leakage (one) and delayed bile leakage (three). All six patients required
      laparotomy. Primary repair with long-arm T tube splinting for 3 months was
      performed for the CBD injury. Religation of the cystic duct was carried out after
      immediate postoperative bile leakage. Laparotomy with T tube choledochostomy only
      was performed in the three patients with delayed bile leakage, and
      hepatojejunostomy Roux-en-Y was undertaken for CBD necrosis. The patient with
      primary repair of the CBD injury required choledochojejunostomy Roux-en-Y 18
      months later for stenosis. Episodes of intermittent cholangitis occurred in the
      patient with CBD necrosis. The outcome for the four patients with bile leakage
      was good. There were no deaths.

PMID- 8298934
TI  - Subumbilical hernia following laparoscopic cholecystectomy.

PMID- 8298935
TI  - Surgical management of perineal and metastatic cutaneous Crohn's disease.
AB  - Skin lesions are the commonest extraintestinal manifestation of Crohn's disease.
      Lesions that develop at sites remote from the gastrointestinal tract and have
      granulomas on histological examination are termed metastatic cutaneous Crohn's
      disease. Management is difficult as medical treatment is often ineffective. This
      report describes the use of surgical debridement of areas of perineal metastatic
      cutaneous Crohn's disease in five patients, all of whom had failed to improve
      after a variety of medical treatments. One patient had a poor result with
      continuing mild perineal discharge and four had a good outcome with complete
      resolution of symptoms and satisfactory cosmetic results.

PMID- 8298936
TI  - Randomized controlled trial comparing laparoscopic and open appendicectomy.
AB  - A study was carried out of 137 patients with a diagnosis of acute appendicitis
      who were randomized to either laparoscopic or open appendicectomy. Patients found
      to have perforated or normal appendices at histological examination were
      excluded. Fifty-two patients undergoing laparoscopic appendicectomy and those
      receiving 57 open procedures were analysed. Laparoscopic appendicectomy took no
      longer than the open procedure (mean 43 versus 40 min). The number of doses of
      pethidine (1 mg per kg body-weight) required in the immediate postoperative
      period did not differ between the two groups but the mean number of doses of oral
      analgesic (naproxen sodium 550 mg twice daily) required was less in patients
      undergoing laparoscopic appendicectomy (2.8 versus 5.0, P < 0.05). There was no
      significant difference between time to resumption of fluid and diet intake and
      length of hospital stay. There were five (9 per cent) wound infections after open
      appendicectomy compared with none after the laparoscopic operation (P < 0.01).
      Patients who underwent laparoscopy returned to full home (17 versus 30 days, P <
      0.01) and social (19 versus 32 days, P < 0.05) activities earlier than those who
      underwent open operation. Laparoscopic appendicectomy may allow reduction in the
      number of wound infections and earlier return to normal activities.

PMID- 8298937
TI  - Colonic obstruction in acute myeloid leukaemia.

PMID- 8298938
TI  - Laparoscopic colorectal surgery: a prospective assessment and current
      perspective.
AB  - Between August 1991 and June 1993, 74 laparoscopic and laparoscopically assisted
      colonic and rectal operations were performed. A variety of procedures were
      carried out including 32 total abdominal colectomies (group 1), 32 segmental
      resections (group 2) and ten constructions of a diverting stoma without formal
      resection (group 3). Indications for surgery were mucosal ulcerative colitis in
      20 patients, carcinoma in 12, polyposis in six, Crohn's disease in seven and
      other conditions in the remaining 29. The 74 comprised 42 male and 32 female
      patients of mean age 45 (range 12-88) years. The median (range) duration of the
      procedure was 3.0 (1.0-6.5) h for the entire group, 3.9 (2.5-6.5) h for group 1,
      2.9 (1.5-5.5) h for group 2 and 1.8 (1.0-2.5) h for group 3. The median (range)
      length of ileus was 3.0 (2-7) days overall; respective times for groups 1-3 were
      3.5 (2-7), 3.0 (2-7) and 2.0 (1-4) days. The median (range) length of
      hospitalization was 7.0 (2-40) days, 8.1 (4-19) days in group 1, 7.0 (4-20) days
      in group 2 and 6.0 (2-40) days in group 3. Ten patients (14 per cent) developed
      intraoperative and 15 (20 per cent) postoperative complications; there were no
      deaths. These results failed to confirm any significant advantages of
      laparoscopic or laparoscopically assisted colorectal surgery. Specifically,
      neither the operating time, nor length of ileus, nor length of hospitalization
      was improved over standard procedures. Advances in technology and surgical
      technique may improve such findings in the future.

PMID- 8298939
TI  - New technique for sigmoid colectomy.
AB  - A combination of laparoscopic and rectoscopic procedures has enabled complete
      resection of the sigmoid colon and eliminated the need for minilaparotomy when
      constructing the anastomosis or withdrawing the specimen. This combined procedure
      was performed in different ways in a series of animal models until the definitive
      technique had been standardized. These techniques were then successfully used in
      15 consecutive medium-sized pigs. Histological evaluation of the specimens,
      including the anastomosis (examined 2-3 weeks after operation) confirmed the
      efficacy and safety of the method.

PMID- 8298940
TI  - Change towards earlier stage at presentation of colorectal cancer.
AB  - A study was carried out to investigate the change in stage at presentation of
      patients with colorectal cancer over 10 years. Cases were identified from the
      control group of subjects enrolled into a randomized controlled study based on
      Haemoccult screening for colorectal neoplasia. Of 405 subjects in the control
      group (presenting with symptomatic colorectal cancer, 206 presented before 1989
      and 199 since then. The number of patients with Dukes' stage A carcinoma
      diagnosed since 1989 rose from 21 (10.4 per cent) to 35 (18.1 per cent); this
      change occurred for rectosigmoid tumours (9.9 per cent before 1989, 28 per cent
      after 1989) but not for colonic cancer (10.9 per cent before 1989, 11.5 per cent
      thereafter). An increase in the proportion of patients with symptomatic early
      stage rectosigmoid cancer has been observed in the past 10 years. No such change
      occurred in those with colonic cancer. This may reflect a change in awareness of
      te disease and its symptoms by patients and general practitioners.

PMID- 8298941
TI  - Follow-up after inguinal herniotomy or surgery for hydrocele in boys.
AB  - A retrospective review of 556 boys who had undergone inguinal herniotomy or
      surgery for hydrocele was carried out to assess the value of early routine
      postoperative follow-up. Of 386 children given an appointment, 319 (82.6 per
      cent) attended. The testis was no longer palpable in the normal scrotal position
      in 12 boys; eight were normal on further review and four required orchidopexy.
      Six hydroceles, all of which resolved, and four contralateral hernias were
      detected. Nineteen boys (4.9 per cent) were referred later with recurrent hernia
      (two patients), ipsilateral high testis (two), or contralateral hernia or
      hydrocele (15). Of 170 children not given a routine appointment, ten (5.9 per
      cent) were subsequently referred back with a transient hydrocele (two) or a
      contralateral hernia (eight). After a total of 440 appointments, eight boys (1.8
      per cent) were found to have a significant abnormality. The rate of referral back
      to hospital was similar in both groups. Early discharge would make more efficient
      use of outpatient resources without significantly affecting overall outcome.

PMID- 8298942
TI  - Total pelvic exenteration: a justified procedure.
AB  - Twenty patients with advanced primary or locally recurrent pelvic tumours treated
      by total pelvic exenteration are described. There wer no operative or
      postoperative deaths. The most frequent postoperative complications appeared to
      be related to previous irradiation. Four patients developed non-fatal intestinal
      complications within 30 days of operation that required further surgery. After a
      mean follow-up of 19 months the crude 2-year survival rate was 40 per cent. This
      procedure is judged to be useful in a selected group of patients.

PMID- 8298943
TI  - Randomized controlled trial of the effect of sulindac on duodenal and rectal
      polyposis and cell proliferation in patients with familial adenomatous polyposis.
AB  - Twenty-four patients with familial adenomatous polyposis who had previously
      undergone prophylactic colectomy and had advanced duodenal polyposis were entered
      into a randomized trial to assess the effect of the non-steroidal anti
      inflammatory drug sulindac on duodenal and rectal polyps. Polyp size and number
      were assessed by videotaped duodenoscopy (and rectoscopy in 14 patients) at entry
      and after 6 months of treatment; the tapes were compared by two assessors who
      were unaware of the randomization and the shuffled chronological order of the
      recordings. Mucosal cell proliferation was measured by in vitro incorporation of
      5-bromo-2'-deoxyuridine. Sulindac therapy was associated with a reduction in
      epithelial cell proliferation in the duodenum (median labelling index (LI) 15.8
      versus 14.4 per cent, P = 0.003) and a trend towards duodenal polyp regression (P
      = 0.12). In the rectum, cell proliferation showed a marked reduction (median LI
      8.5 versus 7.4 per cent, P = 0.018), and significant (P = 0.01) polyp regression
      was seen. Rectal polyposis was less severe than that in the duodenum and
      responded more dramatically. Sulindac is a possible treatment for patients in
      whom rectal polyps have failed to show significant regression after ileorectal
      anastomosis and who are unsuitable for pouch surgery; it may be useful in early
      duodenal polyposis or as an adjunct after duodenal clearance.

PMID- 8298944
TI  - Pouch adenomas in patients with familial adenomatous polyposis.

PMID- 8298945
TI  - Secondary proctectomy and ileal pouch-anal anastomosis after ileorectal
      anastomosis for familial adenomatous polyposis.
AB  - Conversion of ileorectal anastomosis to ileal pouch-anal anastomosis (IPAA) was
      indicated in 29 patients with familial adenomatous polyposis but technically
      impossible in three because of unsuspected pelvic desmoid tumours. There was no
      operative mortality and overall postoperative morbidity and late complication
      rates were no different from those in a group of 120 patients who underwent IPAA
      as a first operative procedure. Unsuspected adenocarcinoma (one invasive, three
      in situ) was found in four patients. The functional results in patients with IPAA
      did not differ from those of ileorectal anastomosis before conversion or from
      those obtained after IPAA as a first-choice procedure. Secondary proctectomy and
      IPAA can be safely offered to patients with ileorectal anastomosis and a high
      risk of rectal cancer.

PMID- 8298946
TI  - Non-therapeutic operations for penetrating trauma: early morbidity and mortality.

PMID- 8298947
TI  - Oesophagogastric intramural implantation anastomosis after oesophagectomy.

PMID- 8298948
TI  - Anal fistula.

PMID- 8298949
TI  - Diaphragm-like strictures of the colon induced by non-steroidal anti-inflammatory
      drugs.

PMID- 8298950
TI  - Cytodiagnosis of breast disease using a liquid suspension medium.

PMID- 8298951
TI  - Superselective intra-arterial chemotherapy with mitomycin for gallbladder cancer.

PMID- 8298952
TI  - Science and suffering--the importance of standards.

PMID- 8298953
TI  - Tuberculosis and AIDS--a deadly combination.

PMID- 8298954
TI  - HIV/AIDS and its implications for the control of animal tuberculosis.
AB  - The HIV/AIDS pandemic is associated with a number of opportunist mycobacterial
      infections, principally tuberculosis and disease due to the avian tubercle
      bacillus, Mycobacterium avium. Tuberculosis occurring early in the course of HIV
      infection is usually caused by M. tuberculosis. However some cases are due to the
      bovine tubercle bacillus, M. bovis, which, in turn, is transmissible from man to
      animals, principally by the aerogenous route although the majority of cases in
      man are non-pulmonary. These two mycobacterial species may be differentiated by
      means of a set of simple tests. The quality and quantity of information on the
      world-wide distribution and prevalence of bovine and human tuberculosis due to M.
      bovis is not uniform. There is a notable paucity of information from the tropics
      but available reports suggest that there are significant levels of bovine
      tuberculosis. If correct, this information has serious public health implications
      in the light of the current HIV/AIDS epidemic. Urgent investigation is required
      so that appropriate control measures can be instituted where indicated and
      possible. The avian tubercle bacillus is a very common opportunistic pathogen in
      the late stage of AIDS but infection leading to disease is extremely rare in
      healthy, HIV-negative persons. Because of its widespread environmental
      distribution, infection by this pathogen cannot be prevented.

PMID- 8298955
TI  - Pulmonary haemodynamics in the exercising horse and their relationship to
      exercise-induced pulmonary haemorrhage.
AB  - Exercise-induced pulmonary haemorrhage (EIPH) is a common occurrence in race
      horses. Although blood in cases of EIPH has been suspected to originate from the
      bronchial circulation, which receives approximately 1% of the left ventricular
      output, physiological evidence has recently emerged to indicate that the
      pulmonary circulation, which receives the entire output of the right ventricle,
      is a more likely source. High transmural pulmonary capillary pressures have been
      shown to cause breaks in the capillary endothelium, basement membrane as well as
      in the alveolar epithelium. Blood constituents escape into the interstitium and
      alveoli through such breaks in the blood-gas barrier--a phenomenon referred to as
      stress failure of pulmonary capillaries. Concomitant measurement of pulmonary
      arterial and venous pressures in strenuously exercising horses have revealed that
      both of these variables increased dramatically such that the intravascular
      pulmonary capillary pressure during exertion at 14 m/s (heart rate of 214
      beats/min) approached 105 cm H2O (79 mmHg). Alveolar pressure during peak
      inhalation is likely to be negative; therefore, it is probable that transmural
      (intravascular minus perivascular) pulmonary capillary pressure of maximally
      exercising horses may be greater than 105 cm of water. Thus, the pulmonary blood
      gas barrier, which has to be thin to provide for adequate diffusion of O2, is
      exposed to very high transmural forces associated with high cardiac output during
      exercise. Recent evidence suggests that the alveolar-capillary membrane may not
      be able to withstand the high transmural forces during maximal exertion, and that
      stress failure of pulmonary capillaries occurs, leading to EIPH. Intravenous
      furosemide premedication 4 h before exercise attenuates the exercise-induced rise
      in pulmonary arterial, capillary and venous pressures and, therefore, may be
      efficacious in reducing or limiting the extent of EIPH in race horses.

PMID- 8298956
TI  - Experimental infection of the conjunctival sac of lambs with Mycoplasma
      conjunctivae.
AB  - Ovine keratoconjunctivitis (OKC) identical to that seen in field cases was
      produced experimentally with 10(6) colony forming units of an isolate of
      Mycoplasma conjunctivae which had been passaged three times in vitro. Cytological
      studies showed that the peak neutrophil count in conjunctival exudate occurred 8
      days after inoculation of the conjunctival sac. Rapid onset of clinical signs in
      the uninoculated eye showed the ease with which the organism could be transferred
      from affected to unaffected eyes.

PMID- 8298957
TI  - The biology of maedi-visna virus--an overview.
AB  - This review aims to summarize the current understanding of the biology of maedi
      visna virus (MVV), the prototype virus of the family lentivirinae. The paper
      provides a short overview of the historical background to the discovery of MVV.
      Detailed descriptions of the structure and organization of the MVV genome and of
      the virion encoded polypeptides are given and the MVV life cycle in vitro and in
      vivo are compared and contrasted and the tropism of the virus discussed. The
      clinical consequences of infection are considered and the mode of transmission,
      immune response to the virus and possible mechanisms of pathogenesis are
      discussed.

PMID- 8298958
TI  - Typing Chlamydia psittaci--a review of methods and recent findings.
AB  - When the present chlamydial classification was established it was recognized that
      a wide variety of types were contained within the arbitrary designation Chlamydia
      psittaci. Early workers relied mostly on observations of growth characteristics
      to differentiate the types of C. psittaci isolated from a wide range of different
      hosts. The differences between isolates were confirmed serologically using a
      variety of tests of which the most sensitive was the micro-immunofluorescence
      (MIF) test which was able to recognize nine immunotypes among the mammalian
      isolates alone. This approach has recently been improved by the use of monoclonal
      antibodies in the MIF test which has confirmed most of the mammalian immunotypes
      and divided the avian strains into four groups. Studies on the nucleic acid of C.
      psittaci isolates show clear differences in the size distribution of DNA
      fragments produced by restriction endonuclease digestion of the genomes of the
      various types. Most importantly, studies of DNA/DNA homologies showed that at
      least four of the types identified by biological, serological and restriction
      endonuclease tests were sufficiently different to be considered separate species.
      Most recently, attention has been focused on DNA sequence comparisons of C.
      psittaci genes amplified by the polymerase chain reaction (PCR). The usual target
      has been the major outer membrane protein gene for which much sequence
      information is now available. The combination of PCR and MIF with monoclonals has
      provided a set of practical techniques with which all chlamydial isolates can be
      detected and typed with relative ease. It is likely that these developments will
      lead to the reclassification of the genus and, hopefully, a rapid increase of our
      understanding of the diseases caused by C. psittaci.

PMID- 8298959
TI  - A critical evaluation of ultrasonic monitoring of superovulation in cattle.
AB  - This study evaluated real time B-mode ultrasonic monitoring for scanning ovaries
      of cows superovulated using eCG (1500 or 3000 i.u.). Follicular growth was
      monitored after stimulation and follicles categorized according to size. Numbers
      of large (> or = 10 mm) follicles correlated weakly (r = 0.31) with numbers of
      luteal structures formed subsequently. Timing of ovulation was confirmed by
      comparison with peak LH and plasma progesterone concentrations. Ovulation was
      visible on scanning but quantitation of corpora haemorrhagica was not accurate in
      superovulated ovaries. Luteal structures counted at scanning correlated
      significantly with findings at post mortem (r = 0.75; P < 0.01) but enumeration
      of structures was inaccurate. Scanning consistently underestimated luteal
      structures. Numbers of observed luteal structures correlated weakly with embryo
      recovery (r = 0.36). It was concluded that the presence of luteinized follicles
      greatly reduced the accuracy of identification of structures in superovulated
      ovaries.

PMID- 8298960
TI  - The goat as a model for Corynebacterium renale pyelonephritis.
AB  - Nubian goats were experimentally infected with Corynebacterium renale type II by
      either the intravenous or intraurethral routes using infection rates of 1.75 x
      10(10), 7.08 x 10(19) or 5 x 10(23) organisms. All inoculated goats were
      anorexic, lost weight and became dull or depressed. Albuminuria, pyuria and
      epithelial casts were noted in the urine. Following intravenous challenge the
      animals showed a dose-related elevation of serum ammonia, urea, and creatinine
      with significant changes in haemoglobin concentration, packed cell volume and
      leucocyte counts. A mild to severe (sometimes haemorrhagic) cystitis and
      urethritis and a mild nephrosis were noted post mortem and mucoserous or
      mucogelatinous non-purulent discharges were present in the renal pelvis. The
      findings are compared to the naturally occurring C. renale pyelonephritis in
      cattle and the suitability of the goat as a model for that disease is discussed.

PMID- 8298961
TI  - Increases in striatal acetylcholine by SKF-38393 are mediated through D1 dopamine
      receptors in striatum and not the frontal cortex.
AB  - It has been proposed by some that the D1 receptor effects are mediated through
      striatal actions while others have suggested that they are determined indirectly
      through the frontal cortex. The experiments reported here represent a further
      attempt to resolve this controversy. It was found that focal applications of the
      inactive and active enantiomers of SKF-38393 (a D1 dopamine receptor agonist) to
      the rat striatum via reverse dialysis increased extracellular acetylcholine (ACh)
      in a stereoselective manner. Infusions of SKF-38393 into the frontal cortex, on
      the other hand, were ineffective in altering striatal ACh. Furthermore, partial
      hemisections caudal to the frontal cortex did not alter the ability of
      systemically administrated SKF-38393 to increase striatal ACh. Taken together,
      these results suggest that at least some of the effects of D1 receptor agonists
      on striatal cholinergic function are mediated through actions in the striatum and
      not the frontal cortex.

PMID- 8298962
TI  - Binding of vascular heparan sulfate proteoglycan to Alzheimer's amyloid precursor
      protein is mediated in part by the N-terminal region of A4 peptide.
AB  - The exact mechanisms of deposition and accumulation of amyloid in senile plaques
      and in blood vessels in Alzheimer's disease remain unknown. Heparan sulfate
      proteoglycans may play an important role in amyloid deposition in Alzheimer's
      disease. Previous investigations have demonstrated high affinity binding between
      heparan sulfate proteoglycans and the amyloid precursor, as well as with the A4
      peptide. In the current studies, a specific vascular heparan sulfate proteoglycan
      found in senile plaques bound with high affinity to two amyloid protein
      precursors (APP695 and APP770). Vascular heparan sulfate proteoglycan also bound
      the Alzheimer's amyloid A4 peptide, and not other amyloid protein precursor
      regions studied, with high affinity. Both heparan sulfate glycosaminoglycan
      chains and chemically deglycosylated vascular heparan sulfate proteoglycan
      protein core bound to A4. High affinity interactions between vascular heparan
      sulfate proteoglycan and the A4 peptide may play a role in the process of
      amyloidogenesis in Alzheimer's disease, by localizing the site of deposition of
      A4, protecting A4 from further proteolysis, or by promoting aggregation and
      fibril formation.

PMID- 8298963
TI  - Light induces expression of fos-related proteins within gastrin-releasing peptide
      neurons in the rat suprachiasmatic nucleus.
AB  - The present study was conducted to determine whether the photic induction of c
      fos expression in the rat suprachiasmatic nucleus (SCN) occurs within neurons
      containing gastrin-releasing peptide (GRP) and/or vasoactive intestinal
      polypeptide (VIP) because these peptidergic cells are closely associated with
      retinal projections to the ventrolateral subfield. Using dual immunostaining and
      thin sectioning techniques, the ventrolateral SCN of light-exposed rats was
      examined for evidence of individual neurons coexpressing nuclear immunostaining
      for c-fos proteins (Fos) with cytoplasmic immunoreactivity for GRP or VIP. In all
      animals, the photic induction of Fos expression in the SCN was mainly confined to
      cells segregated within the ventrolateral subfield and was evident in
      approximately 40% of the SCN neurons with cytoplasmic immunoreactivity for GRP.
      However, neurons coexpressing Fos and GRP comprised only a small fraction of the
      total number of cells within the ventrolateral SCN exhibiting light-induced Fos
      immunoreactivity. No sign of Fos expression was detected within VIP
      immunoreactive perikarya in the ventrolateral SCN of light-treated rats. These
      results demonstrate that light induces Fos expression in a number of GRP
      containing neurons within the SCN, suggesting that these peptidergic cells may
      process photic information mediating circadian entrainment.

PMID- 8298964
TI  - Endogenous codeine and morphine are stored in specific brain neurons.
AB  - Codeine and morphine have been detected in mammalian brain by radioimmunoassay
      (RIA), and in brain and other tissues by gas-chromatography/mass-spectrometry
      (GCMS) in different laboratories. It has been also shown that rat liver can
      synthesize the skeleton of the morphine molecule, thus suggesting that this
      alkaloid, which is the prototype of mu-receptor agonists, plays a physiological
      role in brain. We report the presence of morphine-like immunoreactive compounds
      inside the cell body, fibers and terminals of neurons in different brain areas.
      Moreover, neurons localized in the same brain areas were capable of accumulating
      and storing [3H]morphine slowly infused intracerebroventricularly (i.c.v.)
      through an osmotic minipump.

PMID- 8298965
TI  - Neuronal plasticity induced by self-stimulation rewarding experience in rats--a
      study on alteration in dendritic branching in pyramidal neurons of hippocampus
      and motor cortex.
AB  - Self-stimulation rewarding experience promoted structural changes in pyramidal
      neurons of the CA3 region of the hippocampus and the Vth layer of the motor
      cortex in adult male Wistar rats. Self-stimulation experience was allowed for 1 h
      daily for a duration of 10 days through bipolar electrodes placed bilaterally in
      lateral hypothalamus and substantia nigra--ventral tegmental area. At the end of
      10 days, rats were sacrificed, and rapid Golgi examination of the CA3 hippocampal
      and layer V pyramidal neurons of the motor cortex was made for a grand total of
      1600 neurons from 80 rats divided into 4 groups. The neurons of the self
      stimulation experienced (SS) group revealed a significant (ANOVA, F-test)
      increase in dendritic branching in the perisomatic domains. Such changes were not
      observed in neurons of sham control (SH), experimenter administered stimulation
      (EA) and normal control (NC) groups. SS animals also showed a significant
      increase in the thickness of lacunosum and radiatum laminae of CA3 neurons of the
      hippocampus. Our results reveal that both limbic and neocortical neurons undergo
      changes in dendritic branching patterns due to self-stimulation rewarding
      experience. It is tempting to hypothesize that neuronal plasticity is the result
      of motivation and learning experienced by rats which underwent self-stimulation.

PMID- 8298966
TI  - Immunohistochemical detection of raf protein kinase in cerebral cortical areas of
      adult guinea pigs and rats.
AB  - The raf protooncogenes are the cellular counterparts of the v-raf oncogene
      expressed by a murine sarcoma virus. The raf protooncogenes encode cytoplasmic
      serine/threonine-specific protein kinases which can be activated from different
      growth factor receptors by phosphorylation. The mRNAs of raf protooncogenes are
      found in a large variety of normal adult tissues, including the central nervous
      system. As concerns the distribution and localization of their protein products
      (the raf kinases), very few data are to be found in the literature. This is the
      first detailed description of their light microscopic localization in neocortical
      and allocortical areas of rodents. Preembedding immunohistochemical studies were
      performed on vibratome sections from the brains of adult guinea pigs and albino
      rats. The localizations of two isoenzymes, raf-1 kinase and B-raf kinase, were
      studied with the help of isoenzyme-specific polyclonal antibodies. Both of the
      antibodies detected raf protein-like immunoreactivity in many neurons and
      scattered glial cells of the sensory neocortex, and the cingular, pyriform,
      perirhinal and entorhinal allocortical areas. Pyramidal and non-pyramidal cells
      of Ammon's horn, granule cells of the dentate fascia and the large neurons in the
      hilar region were immunoreactive, too. The findings indicated that B-raf protein
      kinase and raf-1 kinase are present almost ubiquitously in the neurons of the
      investigated cortical structures. The intensity of staining obtained with serial
      dilutions of the antibodies indicated that the cytoplasmic concentration of B-raf
      kinase is tended to be higher than that of raf-1 kinase. The present findings
      suggested that the raf kinases are localized in postsynaptic structures, mainly
      in dendrites and cell bodies. Their cytosolic localization and their ability to
      undergo intracellular translocation during activation and phosphorylation raise
      the possibility that they play a pivotal role in the intracellular signaling of
      neurons.

PMID- 8298967
TI  - Differential sensitivity of tetrodotoxin-sensitive and tetrodotoxin-resistant
      sodium channels to the insecticide allethrin in rat dorsal root ganglion neurons.
AB  - The pyrethroid insecticides are known to modify neuronal sodium channels to cause
      a prolongation of whole cell current. The sodium channels expressed in the dorsal
      root ganglion neurons of the rat are of two types, one highly sensitive to
      tetrodotoxin and the other highly resistant to tetrodotoxin. The pyrethroid
      allethrin exerted profound effects on tetrodotoxin-resistant sodium channels
      while causing minimal effects on tetrodotoxin-sensitive sodium channels. Currents
      derived from tetrodotoxin-resistant sodium channels were greatly prolonged during
      a step depolarization; the tail currents upon repolarization were also augmented
      and prolonged. In the tetrodotoxin-sensitive sodium channel currents, these
      changes caused by allethrin were much smaller or negligible. The activation and
      inactivation voltages of tetrodotoxin-resistant peak sodium currents were not
      significantly altered by allethrin. The differential action of allethrin on the
      two types of sodium channels would be important not only in identifying the
      target molecular structure but also in interpreting the symptoms of poisoning in
      mammals.

PMID- 8298968
TI  - Ultrastructural localization of neuropeptide Y-immunoreactivity in the axonal
      reticulum elements, accumulating anterogradely in transected rat sciatic nerve.
AB  - The detection of dopamine-beta-hydroxylase and cytochrome B561 on the membranes
      of the axonal reticulum demonstrated that in sympathetic neurons the different
      compartments of the axonal reticulum participate in the formation of
      neurosecretory vesicles. In the present study we tried to reveal that the
      components of the vesicular content are also channeled along the axonal
      reticulum, by examining whether neuropeptide Y could be localized in elements of
      the axonal reticulum. Therefore 6 h transected rat sciatic nerve was embedded in
      glycolmethacrylate and an immunogold labeling was performed. Counterstaining with
      phosphotungstic acid at low pH selectively contrasted the accumulated axonal
      reticulum elements and associated granules. In the non-myelinated axons gold
      labeling was localized on granules and on tubular and granular profiles,
      demonstrating the presence of neuropeptide Y in the accumulated axonal reticulum
      elements. This indicates that neuropeptides are indeed transported via the axonal
      reticulum to the nerve ending and suggests that the accumulation of large dense
      cored vesicles at a block is mainly due to local new formation rather than down
      transport.

PMID- 8298969
TI  - A high-dose methamphetamine regimen results in long-lasting deficits on
      performance of a reaction-time task.
AB  - Rats were treated with a high-dose methamphetamine (METH) regimen (50 mg/kg 3
      times at 8-h intervals). Three weeks after treatment, they were trained on a
      reaction-time task. METH-treated rats failed to improve over a 3-month test
      period, while controls demonstrated a gradual increase in reaction-time speed
      over the same test period. METH treatment resulted in a significant dopamine
      depletions in the caudate/putamen and nucleus accumbens/olfactory tubercle;
      significant serotonin depletions in caudate/putamen, nucleus accumbens/olfactory
      tubercle, somatosensory cortex, amygdala and hippocampus. In contrast to the
      decreases observed in other brain regions, serotonin levels were significantly
      greater than controls in the hypothalamus. It is suggested that the behavioral
      impairment in the METH-treated animals is due to (a) serotonin and/or dopamine
      depletions or (b) abnormal or hyper-innervation of serotonin to the hypothalamus.

PMID- 8298970
TI  - Glycine-induced changes in synaptic efficacy in hippocampal slices involve
      changes in AMPA receptors.
AB  - Brief applications of high glycine concentrations to hippocampal slices have been
      shown to produce long-lasting changes in synaptic efficacy. In the present study,
      we show that glycine application transiently and reversibly increases the
      amplitude and prolongs the duration of synaptic potentials mediated by N-methyl-D
      aspartate (NMDA) receptors. The long-lasting changes in synaptic potentials
      mediated by AMPA receptors are correlated with changes in the binding of
      [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) to
      membranes prepared from glycine-treated slices. The changes in binding properties
      of AMPA receptors in adult slices are due to an increase in affinity of the
      agonist for the receptor. Furthermore, glycine-induced increases in [3H]AMPA
      binding and in synaptic potentials in adult hippocampal slices are markedly
      reduced in the presence of low extracellular calcium or of the phospholipase
      inhibitor bromophenacylbromide. Finally, glycine-induced potentiation of synaptic
      potentials is associated with an increased potency of the glutamate receptor
      antagonist, 6,7-dinitroquinoxaline (DNQX), to inhibit synaptic potentials. The
      results indicate that glycine-induced changes in synaptic efficacy are likely
      triggered by the activation of NMDA receptors and expressed by changes in the
      properties of AMPA receptors. As similar events underly long-term potentiation
      (LTP), this phenomenon might provide important clues to elucidate the molecular
      mechanisms involved in LTP maintenance.

PMID- 8298971
TI  - Bidirectional modulation of stimulated cortical acetylcholine release by
      benzodiazepine receptor ligands.
AB  - In vivo microdialysis was used to determine the ability of benzodiazepine
      receptor (BZR) ligands to modulate stimulated cortical acetylcholine (ACh) efflux
      in awake, freely-moving Fischer-344/BNNia rats. Cortical ACh efflux was reliably
      enhanced during presentation of a complex stimulus (exposure to darkness coupled
      with presentation of a small amount of palatable food) in animals entrained with
      that stimulus. Administration of the BZR selective inverse agonist ZK 93,426 (5.0
      mg/kg, i.p.) potentiated the ability of the darkness/food stimulus to enhance
      efflux, whereas administration of the BZR full agonist, chlordiazepoxide (5.0
      mg/kg, i.p.) blocked the enhancement. The interaction of the BZR ligands with the
      entrained stimulus in affecting cortical ACh efflux was not secondary to effects
      on motor activity. These results, combined with results from a previous study,
      suggest that modulation of cortical ACh efflux by BZR ligands is bidirectional
      and dependent on the level of activity within cortical cholinergic neurons. This
      relationship enables the trans-synaptic stimulation of cortical ACh transmission
      by BZR inverse agonists to be most effective during behavioral activities which
      recruit the basal forebrain cholinergic system.

PMID- 8298972
TI  - A descriptive and quantitative morphometric study of long-term mouse adrenal
      medulla grafts implanted into the putamen: effect of nerve growth factor injected
      at grafting.
AB  - Mouse adrenal medulla grafts were evaluated morphologically and quantitatively
      after implantation into the mouse putamen, either alone or with nerve growth
      factor (NGF) injected at grafting. Specific antibodies were used to determine the
      expression of neurofilaments, dopamine (DA) and phenylethanolamine-N-methyl
      transferase (PNMT). Three months after grafting, the survival rate and size
      volume of chromaffin cells were significantly greater in the grafts containing
      NGF, and increasing numbers of intermediate cell types (e.g. chromaffin cells
      transforming into neurons), and of neuron-like cells seemed to have formed.
      Chromaffin cells stained positively for DA and PNMT, but only a few chromaffin
      like processes stained for neurofilaments. A neuronal network of adrenal medulla
      grafts was observed, consisting of non-myelinated nerve fibers, nerve terminals
      and chromaffin-like processes. In all grafts the synapses on chromaffin cells
      were mainly small, symmetrical or asymmetrical (about 1-2 microns in diameter)
      with round, small clear synaptic vesicles. Nerve terminals were not
      immunoreactive to dopamine or PNMT. These results show that a single injection of
      NGF at grafting influences the survival and differentiation of chromaffin cells.
      This study suggests that adrenal medulla grafts may integrate into the putamen.

PMID- 8298973
TI  - Morphine fails to produce tolerance when administered in the presence of formalin
      pain in rats.
AB  - The present study examined the development of tolerance to morphine analgesia
      under conditions in which morphine was administered in the presence or absence of
      pain induced by subcutaneous injection of 50 microliters of 2.5% formalin into
      the hind paw of rats. Animals were injected with morphine (25 mg/kg, i.p.) or
      saline for 3 consecutive days either in the presence of pain (10 min after
      formalin injection) or in the absence of pain (6 h prior to formalin injection).
      On the 4th day, tolerance to the analgesic effect of test doses of morphine (6 or
      10 mg/kg) was assessed in the formalin and tail-flick tests, respectively.
      Significant tolerance in both tests was observed in animals receiving morphine in
      the absence of pain during the tolerance induction period, but not in animals
      receiving morphine in the presence of pain.

PMID- 8298974
TI  - Sigma binding parameters in developing rats predict behavioral efficacy of a
      sigma ligand.
AB  - The relationship between sigma binding and the behavioral efficacy of a selective
      sigma ligand was examined in rats of varying ages (30, 45, 60, 75, 90, and 150
      days old). Scatchard analyses of the binding of the sigma radioligand [3H]1,3-di
      o-tolylguanidine ([3H]DTG) to brain membranes revealed significant age-related
      differences in binding to both crude synaptosomal and microsomal fractions. The
      functional significance of these developmental changes in sigma ligand binding
      was studied by determining the postural effects of rubral microinjections of DTG
      in age-matched littermates of rats used in the binding studies. The degree of
      dystonia produced by a single dose of DTG was significantly correlated with the
      amount of [3H]DTG bound to rat brain synaptosomal membranes at low but not at
      high concentrations. No significant correlation between binding to the microsomal
      fraction and drug efficacy was observed. These experimental results were in good
      agreement with predicted amounts bound as estimated from a Scatchard analysis of
      the data. The results suggest that sigma binding sites found in brain
      synaptosomal membranes are functional receptors involved in the control of
      movement and posture.

PMID- 8298975
TI  - Domoic acid-treated cynomolgus monkeys (M. fascicularis): effects of dose on
      hippocampal neuronal and terminal degeneration.
AB  - Domoic acid is a tricarboxylic amino acid (structurally related to kainic acid
      and glutamic acid) that is found in the environment as a contaminant of some
      seafood. To determine the nature of any neurological damage caused by domoate, as
      well as the minimum neurotoxic dose, juvenile and adult monkeys were dosed
      intravenously with domoate at one of a range of doses from 0.25 to 4 mg/kg. When
      animals were perfused one week later, histochemical staining using a silver
      method to reveal degenerating axons and cell bodies showed two distinct types of
      hippocampal lesions. One lesion, termed 'Type A', was a small focal area of
      silver grains restricted to CA2 stratum lucidum, the site of greatest kainic acid
      receptor concentration in the brain. Type A lesions occurred over a dose range of
      0.5 to 2.0 mg/kg in juvenile animals and 0.5 to 1.0 mg/kg in adult animals. No
      mortality occurred in any of the juvenile monkeys, but one juvenile animal that
      received 4.0 mg/kg sustained a second type of lesion, termed 'Type B',
      characterized by widespread damage to pyramidal neurons and axon terminals of
      CA4, CA3, CA2, CA1, and subiculum subfields of the hippocampus. Doses of more
      than 1.0 mg/kg in the adult monkeys either proved lethal or resulted in Type B
      lesions. Induction of c-fos protein had occurred in the hippocampal dentate gyrus
      and CA1 regions of moribund animals perfused within hours of their initial
      dose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298976
TI  - Recruitment of inhibition by enhanced activation of synaptic NMDA responses in
      the rat cerebral cortex.
AB  - Intracellular recordings of layer V neurons from rat neocortical slices were
      obtained to examine the effects of reducing extracellular magnesium on
      inhibition. Magnesium-free solutions induced interictal and ictal-like events in
      cortical neurons. Changes in synaptic events underlying epileptogenesis were
      studied when extracellular calcium was raised (from 2 to 3-7 mM) since this
      delayed seizure activity. With increasing time of exposure of cells to magnesium
      free solutions, there was a significant increase in the size and duration of both
      the depolarizing and slow synaptic hyperpolarizing responses, but the fast
      synaptic hyperpolarization significantly declined in amplitude. When cells were
      recorded with cesium acetate-filled microelectrodes slow hyperpolarizing
      responses were blocked, but depolarization of cells to 0 mV allowed an isolated
      fast hyperpolarizing response to be recorded following synaptic stimulation. The
      amplitude of this response was unchanged after exposure to magnesium-free
      solutions. Synaptic responses of cells initially bathed in an N-methyl-D
      aspartate (NMDA) antagonist (CPP) were unchanged by subsequent exposure to
      magnesium-free solutions. CPP exposure by itself caused a decrease in
      depolarization duration, increase in fast hyperpolarizing amplitude, and decrease
      in slow hyperpolarization amplitude and duration. When the fast hyperpolarization
      was viewed in isolation (cesium recording electrodes) at 0 mV, the amplitude of
      this event was unchanged by exposure to CPP. Given these results stimulus
      response characteristics of neocortical neurons were reassessed under control
      conditions. With higher intensity stimuli larger depolarizing and slow
      hyperpolarizing responses were evoked, but the fast hyperpolarization showed a
      decremental response. These effects were reversed when CPP was added. When NMDA
      activity was enhanced by exposure to magnesium-free solutions or electrical
      stimulation, the amplitude of excitatory events and slow hyperpolarizations
      increased, but fast inhibitory responses showed limited capacity for incremental
      recruitment. This suggests fast inhibition is saturated (maximal) at submaximal
      levels of excitation, and can be overcome by increasing levels of excitation.
      Such a process is active under physiological conditions, altering the efficacy of
      inhibition.

PMID- 8298977
TI  - Identification of the metabotropic glutamate receptor-1 protein in the rat
      trigeminal ganglion.
AB  - Anti-metabotropic glutamate receptor-1 monoclonal antibody was raised and applied
      for immunohistochemistry in the rat trigeminal ganglion. The antibody detected
      145-kDa single band of protein in the immunoblot analysis. In
      immunohistochemistry, neurons in the trigeminal ganglion showed immunostaining
      with various intensity, almost irrespective of their cell size. The results
      indicate that metabotrophic glutamate receptors play an important role in somatic
      sensation together with ionotropic ones.

PMID- 8298978
TI  - Nystatin-perforated patch recordings disclose KA-operated outward currents in rat
      cortical neurons.
AB  - Kainate (KA)-induced responses were studied in acutely dissociated rat cortical
      neurons. KA elicited the inward currents with conventional whole-cell and
      nystatin-perforated patch recordings under voltage-clamp condition. An additional
      outward current was observed only with the perforated patch recording. The
      outward current was due to the activation of K+ current by Ca2+ passing through
      the KA channels. This K+ channel was sensitive to both iberiotoxin and
      tetraethylammonium (TEA)-Cl. This K+ channel may serve to limit the
      depolarization during excessive KA-mediated excitation.

PMID- 8298979
TI  - Iron induced oxidative stress and mitochondrial dysfunction: relevance to
      Parkinson's disease.
AB  - Inactivation of the mitochondrial respiratory chain in response to iron-induced
      oxidative stress has been studied in cultured cells. Iron loading resulted in
      malonaldehyde production, decreased levels of glutathione and reduced specific
      activities of both complexes I and IV of the respiratory chain. These results are
      discussed with respect to idiopathic Parkinson's disease, which is associated
      with increased iron levels and a specific decrease in complex I activity in the
      substantia nigra.

PMID- 8298980
TI  - A subpopulation of chicken primary sensory neurons defined by complete co
      localization of peripherin-and ovalbumin-immunoreactivities.
AB  - In a previous study, we have demonstrated that an ovalbumin-like antigen is
      present within approximately one-half of all neurons of chicken spinal ganglia.
      The current study demonstrates this antigen co-localizes absolutely with neural
      intermediate filament protein (Peripherin) in small to medium-sized neurons of
      spinal ganglia. While the function of ovalbumin in neurons is unknown, its
      precise co-localization with Peripherin suggests a functional role restricted to
      neurons of a defined phenotype.

PMID- 8298981
TI  - Cell-type specific expression of Na+, K(+)-ATPase catalytic subunits in cultured
      neurons and glia: evidence for polarized distribution in neurons.
AB  - Na+,K(+)-ATPase (the sodium pump) is a family of proteins consisting of catalytic
      (alpha) and glycoprotein (beta) subunit isoforms which are differentially
      expressed in excitable tissue. To gain insight into the cell-type distribution of
      sodium pump protein, we determined the expression pattern of fetal rat
      telencephalic cultures, of telencephalic cultures depleted of neurons, and of
      pure astrocyte cultures. Isoform-specific antibodies were used for immunoblotting
      and immunohistochemistry, with supplemental [3H]ouabain binding to assess levels
      of functional alpha 2/alpha 3 protein. The results show that neurons of mixed
      telencephalic cultures uniquely express alpha 3 and high levels of alpha 1. The
      marked similarity in the distribution of microtubule-associated protein-2 and
      alpha 1 immunocytochemical staining strongly suggests that alpha 1 subunits are
      enriched in dendrites. Further, highly correlative growth cone-associated protein
      43 and alpha 3 staining is consistent with a preferential expression of alpha 3
      subunits in axons, which are also characterized by low levels of alpha 1 and no
      alpha 2 immunoreactivity. Process-bearing glia are intimately associated with
      neuronal aggregates and express high levels of both alpha 1 and alpha 2 protein,
      as well as GFAP. Interestingly, polygonal, flat glia not within neuronal
      aggregates are weakly immunopositive only for alpha 1 and GFAP. Pure astrocytic
      cultures possess appreciable alpha 1 protein and GFAP, but lack both alpha 2 and
      alpha 3 immunoreactivity. As predicted by the immunohistochemical findings,
      [3H]ouabain binding was low in pure astrocytic cultures, and much higher in the
      neuron-enriched mixed cultures. These observations confirm that neurons express
      all three catalytic isoforms of the sodium pump. They also suggest that specific
      alpha-isoforms may be polarized to targeted membrane regions of neurons. Further,
      glia intimately associated with neurons express alpha 2, bind significant amounts
      of [3H]ouabain, and possess much higher levels of alpha 1 and GFAP compared to
      glia not near neurons. Thus, neurons may regulate glial sodium pump expression.

PMID- 8298982
TI  - Investigations of the regulation of specific 2-[125I]iodomelatonin binding sites
      in Siberian hamsters by endogenous and exogenous melatonin.
AB  - These studies used quantitative in vitro autoradiography to investigate whether
      endogenous or exogenous melatonin modulate specific 2-[125I]iodomelatonin binding
      sites in the pars tuberalis or suprachiasmatic nuclei of Siberian hamsters.
      Saturation analyses were conducted on tissue sections from hamsters that were
      pinealectomized, exposed to constant illumination (72 h), or injected with
      melatonin, and from hamsters that were treated as controls. High affinity (Kd
      approximately 20-75 pM) specific 2-[125I]iodomelatonin binding sites were
      detected in the suprachiasmatic nuclei and pars tuberalis of all animals. Neither
      pinealectomy nor constant illumination significantly affected either the affinity
      or the density of the specific 2-[125I]iodomelatonin binding sites in either
      region. Melatonin injections led to a decrease in specific 2-[125I]iodomelatonin
      binding to the pars tuberalis at 3-4 h after the last injection. However, washing
      the sections before incubation with 2-[125I]iodomelatonin eliminated this effect,
      suggesting that melatonin was occupying the binding sites rather than decreasing
      their actual number. Furthermore, when hamsters were sacrificed 18 h after the
      last melatonin injection, no effect of melatonin on either the affinity or
      density of specific 2-[125I]iodomelatonin sites was observed. These data suggest
      that 2-[125I]iodomelatonin binding sites in Siberian hamsters are not regulated
      by changes in circulating melatonin levels.

PMID- 8298983
TI  - Benzodiazepines antagonize central corticotropin releasing hormone-induced
      suppression of natural killer cell activity.
AB  - Benzodiazepines have anxiolytic properties and attenuate behavioral stress
      responses induced by corticotropin releasing hormone (CRH). To evaluate the
      effect of benzodiazepines on CRH-induced immune suppression, potent centrally
      acting benzodiazepines were administered prior to central infusion of CRH
      (i.c.v.; 1.0 microgram). CRH induced a significant (P < 0.01) reduction of
      splenic natural killer cell activity which was completely antagonized by
      pretreatment with either diazepam or alprazolam.

PMID- 8298984
TI  - Hippocampal serotonin levels influence the expression of S100 beta detected by
      immunocytochemistry.
AB  - The response of astrocytes to pharmacological alterations of the serotonin (5-HT)
      content of the dorsal area dentata was studied by immunocytochemistry for S100
      beta. Stereological analysis revealed changes in the density of astrocytic
      elements in conditions of 5-HT depletion and elevated 5-HT levels. There was a
      direct relationship between the expression of S100 beta and the level of 5-HT in
      the hippocampal formation. Thus when 5-HT was reduced by PCPA treatment, S100
      beta immunoreactivity was also reduced. The converse of these observations was
      obtained in cases where the 5-HT levels were increased by fluoxetine
      administration. These immunocytochemical data are consistent with previous
      reports of the response of astrocytes to 5-HT in vitro.

PMID- 8298985
TI  - [Leu31,Pro34]neuropeptide Y (NPY), but not NPY 20-36, produces discriminative
      stimulus effects similar to NPY and induces food intake.
AB  - Rats were trained to discriminate between an intracerebroventricular injection of
      1.15 nmol of Neuropeptide Y (NPY) and a sham injection. Rats rapidly learned to
      press the appropriate lever during training. NPY's discriminative stimulus
      effects were compared to those of saline, and 1.15-3.45 nmol [Leu31,Pro34]NPY, a
      Y1 receptor agonist and NPY 20-36, Y2 receptor agonist. [Leu31,Pro34]NPY resulted
      in NPY-appropriate responding, whereas saline and NPY 20-36 did not.
      [Leu31,Pro34]NPY also increased food intake, but NPY 20-36 did not. This suggests
      that NPY's discriminative stimulus and orexigenic effects involve the Y1, but not
      the Y2, receptor.

PMID- 8298986
TI  - Thalamocortical rhythm generation in vitro: extra- and intracellular recordings
      in mouse thalamocortical slices perfused with low Mg2+ medium.
AB  - Mouse thalamocortical slices maintain synaptic connections between thalamus and
      cortex. When perfused with low Mg2+ medium, thalamocortical slices exhibited
      spontaneous thalamocortical 2-6 s long bursts of rhythmic activity every 15-30 s,
      which was potentiated by pentylenetetrazol and abolished by severing
      thalamocortical connections. These oscillations were similar in frequency and
      duration to normal and pathological thalamocortical rhythms in vivo. In vitro
      studies of these thalamocortical rhythms may prove valuable in understanding
      cellular factors important in rhythm generation.

PMID- 8298987
TI  - Norepinephrine transporter sites are decreased in the locus coeruleus in
      Alzheimer's disease.
AB  - The present study determined whether [3H]nisoxetine binding to norepinephrine
      transporter sites would be altered uniformly throughout the locus coeruleus in
      Alzheimer's disease. A significant decrease (P < 0.01) in [3H]nisoxetine binding
      was seen in the mid and caudal regions but not in the rostral region of the locus
      coeruleus. The loss of [3H]nisoxetine binding to norepinephrine transporter sites
      may be attributed to a loss of norepinephrine transporter sites located on
      terminals of noradrenergic neurons in the locus coeruleus in Alzheimer's disease.

PMID- 8298988
TI  - Testosterone effects on paternal behavior and vasopressin immunoreactive
      projections in prairie voles (Microtus ochrogaster).
AB  - Castration reduced paternal responsiveness of male prairie voles (Microtus
      ochrogaster). Castration also reduced the number of vasopressin immunoreactive
      (AVP-ir) cells in the bed nucleus of the stria terminalis (BST) and medial
      amygdaloid nucleus (MA), as well as the density of AVP-ir fibers in the lateral
      septum. Testosterone treatment of castrated voles prevented these changes. The
      similarities in the effects of the hormonal manipulations on paternal
      responsiveness and AVP immunoreactivity provide further support for the
      hypothesis that AVP-ir projections of the BST and MA are implicated in paternal
      behavior.

PMID- 8298990
TI  - Distribution of parvalbumin-containing neurons and lectin-binding perineuronal
      nets in the rat basal forebrain.
AB  - In sections of rat brain treated for Wisteria floribunda agglutinin (WFA)
      labelling the occurrence of parvalbumin (PARV)-, calbindin (CALB)- or choline
      acetyltransferase (ChAT) immunoreactivity was analyzed in the basal forebrain
      using dual-peroxidase and double-fluorescence methods. Only PARV-immunoreactive (
      ir) neurons were surrounded by WFA-labelled, i.e. N-acetylgalactosamine
      containing, perineuronal lattice-like structures known as perineuronal nets. The
      distribution of these nets and PARV-ir cells in the rat basal forebrain was
      documented to obtain detailed data on their co-existence. A remarkable diversity
      in distribution of both markers was observed, as PARV-ir neurons are only
      associated with nets in the medial septal nucleus, the nuclei of the diagonal
      band and the magnocellular preoptic nucleus, but not in the ventral pallidum or
      the substantia innominata/nucleus basalis complex. These differences in the
      neuronal microenvironment may reflect system-related specializations of neurons
      within the basal forebrain nuclei.

PMID- 8298989
TI  - Differential localization of A2a adenosine receptor mRNA with D1 and D2 dopamine
      receptor mRNA in striatal output pathways following a selective lesion of
      striatonigral neurons.
AB  - We have used the suicide transport agent volkensin to produce selective lesions
      of striatonigral neurons. By in situ hybridization histochemistry unilateral
      volkensin injections in the substantia nigra decreased the number of D1 receptor
      mRNA-expressing neurons in the ipsilateral striatum but did not change the number
      of D2 receptor and A2a adenosine receptor mRNA-expressing neurons. These findings
      confirm that striatonigral neurons express D1 receptors and suggest that D2-A2a
      receptor expressing neurons are predominantly localized to other neuronal
      populations within the striatum.

PMID- 8298991
TI  - Bilateral induction of NADPH-diaphorase activity in neocortical and hippocampal
      neurons by unilateral injury.
AB  - Unilateral injury of the cerebral cortex or hippocampus induced a bilateral
      appearance of NADPH-diaphorase in some pyramidal neuronal and glial cells of both
      structures. Only in the cerebral cortex, near the needle track, did some V layer
      pyramidal neurons contain so much of this enzyme that they looked to be stained
      by the Golgi method. The induction of NADPH-diaphorase in a subset of cortical
      and hippocampal neurons in both hemispheres after unilateral injections of either
      cysteamine or artificial cerebro-spinal fluid suggests the existence in the
      isocortex and the hippocampus of a selective signalling system which may play a
      role in recovery of function following local brain damage.

PMID- 8298992
TI  - Release of hypothalamic corticotropin-releasing hormone and arginine-vasopressin
      by interleukin 1 beta and alpha MSH: studies in rats with different
      susceptibility to inflammatory disease.
AB  - The susceptibility of Lewis rats is related to blunted hypothalamic-pituitary
      adrenal (HPA) axis responsiveness to a variety of inflammatory and neuroendocrine
      stimuli. In contrast resistance to inflammatory disease of histocompatible
      Fischer rats is associated with their intact HPA axis responses to the same
      stimuli. We have examined the contribution of IL-1 beta to in vitro corticotropin
      releasing hormone (CRH) and arginine vasopressin (AVP) release from hypothalamic
      explants derived from LEW/N and F344/N rats. The same animal model has been used
      to investigate the regulatory effect of alpha MSH, an immunosuppressive
      neurohormone, on IL-1 beta stimulated CRH and AVP secretion. CRH basal release in
      both strains was similar. However, LEW/N hypothalamic AVP basal secretion was
      significantly elevated. CRH relative response of LEW/N hypothalamic explants to
      IL-1 beta stimulation was lower compared to Fischer, which is consistent with
      their hyporesponsiveness to inflammatory mediators. AVP secretion however, was
      significantly decreased in hypothalamic explants from both strains after 40 min
      exposure to IL-1 beta. alpha MSH suppressed basal CRH and AVP release in both
      LEW/N and F344/N rats and prevented IL-1 beta stimulated CRH secretion in these
      strains. AVP was further diminished in F344/N explants following incubation with
      alpha MSH + IL-1 beta, while LEW/N level was significantly elevated. However, AVP
      levels remained significantly below baseline in explants from both strains after
      final incubation with IL-1 beta. Although our findings indicate a modulatory
      action of alpha MSH in HPA axis regulation in vitro, the physiological importance
      of this phenomenon in Lewis and Fischer rats requires further investigation.

PMID- 8298993
TI  - Quantitative receptor autoradiography demonstrates a differential distribution of
      neuropeptide-Y Y1 and Y2 receptor subtypes in human and rat brain.
AB  - Quantitative receptor autoradiography was performed on sections of rat and human
      brain using [125I]peptide YY ([125I]PYY) to measure the anatomical distribution
      of neuropeptide Y (NPY) receptors. Masking Y1- and Y2-NPY subtypes with the
      agonists (Leu31,Pro34]NPY and NPY13-36, respectively demonstrated a differential
      distribution of Y1 and Y2 receptors between human and rat brain. In human brain,
      the highest density of [125I]PYY binding was found in pyramidal layers (CA4-CA1)
      of hippocampus, head and tail regions of caudate nucleus, locus coeruleus and
      substantia nigra. There was moderate [125I]peptide YY binding to NPY receptors in
      the molecular layers of the hippocampus, frontal and temporal cerebral cortex,
      especially in superficial layers, anterior amygdala, central grey and inferior
      colliculus. Low levels of binding were observed in white matter. The selective Y1
      receptor agonist, [Leu31,Pro34]NPY did not effectively reduce [125I]PYY binding
      to any human brain region examined except for approximately 20-40% of the binding
      sites in the molecular layer of the dentate gyrus, layer IV of the frontal cortex
      and the radiatum and oriens layers of the hippocampal complex. In contrast, the
      Y2 agonist, NPY13-36 was effective at reducing [125I]PYY binding in all human
      brain regions examined. In rat brain, high densities of [125I]PYY binding was
      measured in cerebral cortex, thalamus and inferior colliculus which was sensitive
      to [Leu31,Pro34]NPY. In contrast, high densities of the NPY13-36 sensitive
      binding was found in the hippocampus, striatum and nucleus accumbens. Medium to
      low densities of NPY13-36 sensitive binding was found in medulla and pons. This
      data suggests that human brain contains primarily Y2-type NPY receptors with only
      a few regions expressing Y1-type receptors. No human brain region examined
      contained solely Y1-type receptors. In contrast to human brain, rat brain
      contains regions which express only Y1 receptors as well as regions containing
      only Y2 receptors and regions containing both Y1 and Y2 receptors.

PMID- 8298994
TI  - Control of astrocytosis by interleukin-1 and transforming growth factor-beta 1 in
      human brain.
AB  - Astrocytosis is a common neurocellular manifestation of brain pathology in
      individuals with a variety of diseases. It is comprised of astrocytic hyperplasia
      (an increase in number of astrocytes) and astrocytic hypertrophy (an increase in
      size of astrocytes). The precise cause(s) of astrocytosis remains unknown. We
      morphometrically measured the relative extent of astrocytosis in brains of 22
      individuals who died with seven different diseases. The relative amounts of
      interleukin-1 (IL-1) and transforming growth factor-beta 1 (TGF-beta 1)
      immunoreactive products (IRPs) were next assessed in sections serial to those in
      which astrocytosis was measured because these cytokines were shown in animal and
      in vitro experiments to be associated with astrocytosis. The data demonstrate
      that astrocytosis and these cytokines were co-localized in all examined human
      tissues. Relative increase in density of astrocytes was correlated with the
      increase in total IL-1 but not TGF-beta 1. In contrast, the increase in size of
      astrocytes was correlated with TGF-beta 1 associated only with astrocytes but not
      with total IL-1. Both IL-1 and TGF-beta 1 IRPs were present in GFAP IRP
      containing and other cells, as assessed by double label immunocytochemistry.
      These observations suggest that IL-1 acts on astrocytes by both, paracrine and
      autocrine mechanisms whereas, TGF-beta 1 only acts by an autocrine mechanism.
      Because these correlations were statistically significant and also because a
      change in number and size of astrocytes constitutes the most frequent response of
      astrocytes to several diseases or injury, we conclude that these cytokines may
      mediate the most common pathological change in human brain.

PMID- 8298995
TI  - Action of toosendanin on the membrane current of mouse motor nerve terminals.
AB  - By perineurial recording, the actions of toosendanin on three potassium currents
      and two calcium currents in the nerve terminal were observed in the intercostal
      nerve triangularis stein muscle of the mouse. Toosendanin partially blocked the
      voltage-dependent fast K+ current and irreversibly increased the voltage
      dependent slow Ca2+ current. The increase in the Ca2+ current of the nerve
      terminal accounts for the facilitation of transmitter release and the
      antibotulismic effect of toosendanin.

PMID- 8298996
TI  - Effect of temperature on kainic acid-induced seizures.
AB  - The effects of body temperature on kainic acid-induced seizures and seizure
      related brain damage were examined in rats. In rats with status epilepticus
      induced by intraperitoneal injection of 12 mg/kg of kainic acid (KA), ictal
      discharges were decreased by 50% when body temperature was lowered to 28 degrees
      C and nearly abolished when body temperature was lowered to 23 degrees C. In rats
      with mild hypothermia (28 degrees C), the duration of ictal discharges following
      KA injection was significantly lower than in rats with normal body temperature.
      No detectable hippocampal cell loss was observed in rats with hypothermia to 28
      degrees C whereas gross cell loss in the hippocampus was observed in all rats
      with KA injection at normal body temperature. In contract to hypothermia,
      hyperthermia markedly aggravated the seizures and hippocampal damage induced by
      KA. Following elevation of body temperature to 42 degrees C KA (12 mg/kg)
      resulted in severe seizures and all rats died of tonic seizures within 2 h.
      Furthermore, 6 mg/kg of KA administered to rats with a body temperature of 41-42
      degrees C, resulted in up to 4 h of continuous ictal discharges whereas no
      continuous ictal discharges were observed after the same injections in rats with
      normal body temperature. Histological examination in rats receiving 6 mg/kg of KA
      revealed severe cell loss in the hippocampus in rats with hyperthermia but not in
      rats with normal temperature. These results demonstrate that body temperature
      plays an important role in the control of epileptic seizures and seizure-related
      brain damage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8298997
TI  - Localization of immunoreactive epidermal growth factor receptor in neonatal and
      adult rat hippocampus.
AB  - The regional and developmental expression of epidermal growth factor (EGF)
      receptor in rat hippocampus was investigated utilizing immunocytochemical
      techniques at the light and electron microscopic levels. EGF receptor
      immunoreactivity in adult hippocampus was compared to that found at postnatal day
      7 (P7). While the receptor was observed in P7 hippocampus, immunostaining was
      more prominent in the adult hippocampus, especially in the pyramidal CA2 field.
      Ultrastructural analysis of this region revealed that the receptor was localized
      to the cell bodies of both P7 and adult neurons rather than the axons or
      dendrites. The expression of EGF receptor in selected regions of the adult brain
      was verified by Western blotting. These results demonstrate the presence of EGF
      receptor in rat hippocampus as early as P7, localize the receptor to the
      pyramidal cell body, and establish the hippocampal formation, particularly CA2,
      as a major site of EGF receptor expression in rat brain.

PMID- 8298998
TI  - c-fos and NGFI-A mRNA of rat retina: evidence for light-induced augmentation and
      a role for cholinergic and glutamate receptors.
AB  - When rats are exposed to room light from the dark, there is a transient increase
      of mRNA for the immediate-early genes c-fos and NGFI-A in the retina.
      Augmentation of c-fos and NGFI-A mRNA by light is apparently associated with
      activation of cholinergic nicotinic and muscarinic receptors as it can be
      suppressed by the nicotinic antagonist mecamylamine and the muscarinic antagonist
      atropine. Moreover, the light-induced increase of c-fos mRNA in retina appears to
      be associated with activation of glutamate receptors also as the noncompetitive
      inhibitor of N-methyl-D-aspartate receptors dizocilpine (MK-801) partially
      suppressed the increase of the c-fos message. Light-induced NGFI-A mRNA
      augmentation is apparently modulated by the same receptors. We were unable to
      detect light-induced changes of c-jun mRNA.

PMID- 8298999
TI  - Neuropeptide Y projection from arcuate nucleus to parvocellular division of
      paraventricular nucleus: specific relation to the ingestion of carbohydrate.
AB  - Neuropeptide Y (NPY) injection into the hypothalamic paraventricular nucleus
      (PVN) stimulates feeding behavior and specifically carbohydrate intake in rats.
      The present study investigated the relation between endogenous levels of NPY and
      natural ingestion for carbohydrate. It also examined the possible importance of a
      specific NPY projection in this relationship, which traverses from cell bodies in
      the arcuate nucleus (ARC) to terminals in the parvocellular division of the PVN
      (pPVN). Sprague-Dawley rats were given pure macronutrient diets (carbohydrate,
      protein and fat), and their daily nutrient intake was recorded for 3 weeks. The
      rats were sacrificed, and 8 hypothalamic nuclei were micropunched and examined
      via RIA for endogenous NPY levels. The results demonstrate a strong, positive
      correlation between daily carbohydrate intake and hypothalamic NPY levels. The
      relationship was specific to the pPVN (r = +0.71; P < 0.001), ARC (r = +0.57; P <
      0.001) and dorsomedial nucleus (DMN, r = +0.52; P < 0.01), and was not observed
      in any other hypothalamic area, including the magnocellular division of the PVN.
      In the pPVN, the NPY levels of animals that consumed > 50 kcal of carbohydrate
      (49 pg/microgram protein) were almost twice that of animals that consumed < 20
      kcal of carbohydrate (28 pg/microgram protein: P < 0.01). Furthermore, NPY levels
      in the ARC were positively correlated with NPY in the pPVN and DMN but not any
      other nuclei. No relation between hypothalamic NPY and measures of protein or fat
      ingestion was detected. Levels of NPY were also unrelated to total caloric
      intake, to body weight at sacrifice, and to body weight gain during the 3-week
      measurement period. These results, together with other findings, provide support
      for a role of endogenous NPY and its projection from the ARC to the pPVN, perhaps
      via the DMN, in controlling natural appetite for carbohydrate.

PMID- 8299001
TI  - Effects of pyrethroid insecticides on gap junctional intercellular communications
      in Balb/c3T3 cells by dye-transfer assay.
AB  - The effects of fenvalerate, esfenvalerate, permethrin, cypermethrin,
      deltamethrin, p-chlorophenylisovaleric acid (CPIA, major metabolite of
      fenvalerate) and DDT, a liver tumor promoter, on gap junctional intercellular
      communication (GJIC) were examined in Balb/c3T3 cells by dye-transfer assay.
      Separate groups of Balb/c3T3 cells were exposed to the chemicals for 1 day. On
      the following day, GJIC was measured by counting the number of dye-transferring
      cells per injection of Lucifer Yellow under a fluorescent microscope.
      Fenvalerate, esfenvalerate, permethrin, cypermethrin, deltamethrin and DDT
      inhibited GJIC at noncytotoxic concentrations, while CPIA did not inhibit GJIC
      even at a cytotoxic concentration. It is concluded that the examined pyrethyroid
      insecticides, but not a metabolite, have inhibitory effects on GJIC in Balb/c3T3
      cells.

PMID- 8299000
TI  - Putative roles of inflammation in the dermatopathology of sulfur mustard.

PMID- 8299002
TI  - Modulation of adrenal cell functions by cadmium salts. 1. Cadmium chloride
      effects on basal and ACTH-stimulated steroidogenesis.
AB  - Cultured Y-1 mouse adrenal tumor cells, which secrete 20-alpha-hydroxy-4-pregnen
      3-one (20-DHP), were used to investigate the acute nonlethal effects of
      incremental cadmium chloride (CdCl2) concentrations on basal and maximally
      stimulated steroid secretion. In addition, cumulative CdCl2 effects during 4-hr
      incubations, effect reversibility, and viability were determined. Cells were
      incubated in 1 ml serum-free Eagle's Minimal Essential Medium (FMEM) with or
      without 0.5 IU (ca. 1.5 microM) adrenocorticotropin (ACTH) in the presence or
      absence of CdCl2. Following incubation, cell viability was quantitated using
      trypan blue exclusion. The 20-DHP secreted into the experimental incubation
      medium was measured by radioimmunoassay. CdCl2 levels of 10.0 micrograms/ml or
      greater significantly inhibited basal 30 min steroid secretion in a dose
      dependent manner; ACTH-stimulated steroid secretion was significantly inhibited
      by levels 5.0 micrograms/ml or greater. At least 80% of all control and
      stimulated cells in the presence or absence of cadmium ions excluded trypan blue.
      The reduction in ACTH-stimulated steroid secretion was greater than the reduction
      in basal steroid secretion at any cadmium concentration level. The CdCl2
      concentration that reduced stimulated steroid hormone secretion by 50% (IC50) was
      45.0 micrograms/ml. Exposing Y-1 cells to either 5.0, 10.0, 45.0 or 500.0
      micrograms CdCl2/ml FMEM for periods ranging from 0.5 to 4 hr inhibited ACTH
      stimulated steroid secretion in a time-dependent manner. After 30 min exposure to
      10.0, 45.0 or 500.0 micrograms CdCl2/ml FMEM with or without ACTH, cadmium
      inhibition was irreversible. When 5.0 micrograms CdCl2/ml was used, basal and
      stimulated inhibition was reversible by reincubating in medium containing ACTH
      alone. The relatively greater cadmium effects on ACTH stimulated steroidogenesis
      might suggest that cadmium modulated the rate-limited transducing system between
      the ACTH plasma membrane receptor complex and cholesterol side-chain cleaving
      mitochondrial enzymes. However, cadmium influences on basal secretion indicated
      effects on the non-rate-limited steroidogenic pathway.

PMID- 8299003
TI  - A comparison of the CHO/HGPRT+ and the L5178Y/TK+/- mutation assays using
      suspension treatment and soft agar cloning: results for 10 chemicals.
AB  - The mouse lymphoma assay (MLA) and Chinese hamster ovary (CHO) cell assay are
      sensitive indicators of mutagenicity. The CHO assay has been modified technically
      to permit treatment in suspension and soft agar cloning comparable to the MLA.
      This methodology eliminates the risk of metabolic cooperation and the trauma of
      trypsinization. In addition, a larger population of cells can be treated and
      cloned for mutant selection. In order to compare the effectiveness of the test
      systems, 10 chemicals were evaluated for the induction of forward mutations in
      the CHO and MLA. Several of these chemicals have been reported as clastogenic;
      therefore, abbreviated colony sizing was performed to gauge the extent of genetic
      damage to the MLA cells. Both test systems detected benzo[a]pyrene, mitomycin C,
      acridine orange, and proflavin, and, with the exception of proflavin, more large
      colonies were present than small colonies. The suspect clastogen, phenytoin, was
      not mutagenic in the MLA and produced inconclusive results in the CHO. Ethidium
      bromide, a clastogen and a bacterial mutagen, was not mutagenic in either the MLA
      or CHO. Four compounds (p-aminophenol, benzoin, methoxychlor, and pyrene) were
      positive in the MLA, generally inducing a large number of small colonies, while
      demonstrating no mutagenic activity in the CHO assay. They have also been shown
      to be generally nongenotoxic in other test systems. Overall, the modified CHO
      assay did not appear to be better than the MLA for the detection of mutagenic
      agents. However, the MLA does appear to have lower specificity.

PMID- 8299004
TI  - Biochemical manipulation of intracellular glutathione levels influences
      cytotoxicity to isolated human lymphocytes by sulfur mustard.
AB  - Glutathione (GSH) is the major nonprotein thiol that can protect cells from
      damage due to electrophilic alkylating agents by forming conjugates with the
      agent. Sulfur mustard (HD) is an electrophilic alkylating agent that has potent
      mutagenic, carcinogenic, cytotoxic, and vesicant properties. Compounds that
      elevate or reduce intracellular levels of GSH may produce changes in cytotoxicity
      induced by sulfur mustard. Pretreatment of human peripheral blood lymphocytes
      (PBL) for 72 hr with 1 mM buthionine sulfoximine (BSO), which reduces
      intracellular GSH content to approximately 26% of control, appears to sensitize
      these in vitro cells to the cytotoxic effects of 10 microM HD but not to higher
      HD concentrations. Pretreatment of PBL for 48 hr with 10 mM N-acetyl cysteine
      (NAC), which elevates intracellular glutathione levels to 122% of control,
      appears to partially protect these in vitro cells from the cytotoxic effects of
      10 microM HD but not to higher HD concentrations. Augmentation of intracellular
      levels of glutathione may provide partial protection against cytotoxicity of
      sulfur mustard.

PMID- 8299005
TI  - Sulfur mustard-increased proteolysis following in vitro and in vivo exposures.
AB  - The pathologic mechanisms underlying sulfur mustard (HD)-induced skin vesication
      are as yet undefined. Papirmeister et al. (1985) postulate enhanced proteolytic
      activity as a proximate cause of HD-induced cutaneous injury. Using a chromogenic
      peptide substrate assay, we previously reported that in vitro exposure of cell
      cultures to HD enhances proteolytic activity. We have continued our investigation
      of HD-increased proteolytic activity in vitro and have expanded our studies to
      include an in vivo animal model for HD exposure. In vitro exposure of human
      peripheral blood lymphocytes (PBL) to HD demonstrated that the increase in
      proteolytic activity is both time- and temperature-dependent. Using a panel of 10
      protease substrates, we established that the HD-increased proteolysis was
      markedly different from that generated by plasminogen activator. The hairless
      guinea pig is an animal model used for the study of HD-induced dermal pathology.
      When control and HD-exposed PBL and hairless guinea pig skin where examined,
      similarities in their protease substrate reactivities were observed. HD-exposed
      hairless guinea pig skin biopsies demonstrated increased proteolytic activity
      that was time-dependent. The HD-increased proteolytic response was similar in
      both in vitro and in vivo studies and may be useful for elucidating both the
      mechanism of HD-induced vesication and potential treatment compounds.

PMID- 8299006
TI  - Development and characterization of a rainbow trout liver cell line expressing
      cytochrome P450-dependent monooxygenase activity.
AB  - A cell line, RTL-W1, has been developed from the normal liver of an adult rainbow
      trout by proteolytic dissociation of liver fragments. RTL-W1 can be grown
      routinely in the basal medium, L-15, supplemented with 5% fetal bovine serum. In
      this medium, the cells have been passaged approximately 100 times over an 8-year
      period. The cells do not form colonies or grow in soft agar. The cultures are
      heteroploid. The cell shape was predominantly polygonal or epithelial-like, but
      as cultures became confluent, bipolar or fibroblast-like cells appeared. Among
      the prominent ultrastructural features of RTL-W1 were distended endoplasmic
      reticulum and desmosomes. Benzo[a]pyrene was cytotoxic to RTL-W1. Activity for
      the enzyme, 7-ethoxyresorufin O-deethylase (EROD), which is a measure of the
      cytochrome P4501A1 protein, increased dramatically in RTL-W1 upon their exposure
      to increasing concentrations of either beta-naphthoflavone (BNF) or 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). With these properties, RTL-W1 should be
      useful for studying the expression of the cytochrome P450 enzymes and as a tool
      for assessing the toxic potency of environmental contaminants.

PMID- 8299007
TI  - Cesium ions influence cultured cell behavior by modifying specific subcellular
      components: the role of membranes and of the cytoskeleton.
AB  - The exposure of the epidermoid cell line A431 to different concentrations of CsCl
      was assessed using different methodological approaches. Two different effects
      were detected depending upon the concentration of the agent: at low
      concentrations, cell modification was represented mainly by a very pronounced
      cell flattening and an alteration of the cell-to-cell contacts, interpreted as an
      increase in cell adhesion. At higher concentrations, a clear pathogenic effect
      was observed that allowed the formulation of the hypothesis that specific
      mechanisms of toxicity at the subcellular level involving mitochondrial and
      cytoskeletal function can exist. In addition, membrane order parameters, as
      detected by electron paramagnetic resonance (EPR) spectroscopy, displayed a dose
      dependent increase in membrane rigidity. Results reported here seem to suggest
      that cesium ions can enter the cell, modify plasma membrane integrity and alter
      some specific cytoplasmic components, e.g. the cytoskeleton. Considering that
      environmental contamination by cesium as a result of radioactive fallout is of
      major importance and that few data are available thus far on this matter, this
      study provides evidence for the possible mechanisms of action of the non
      radioactive form of this ion in cells.

PMID- 8299009
TI  - Regulatory aspects of drug use in performance horses.
AB  - The control of drug use in performance horses and the policing of rules and
      regulations to prevent unauthorized drug use are important tasks for agencies
      overseeing equestrian events. This article describes the roles of the American
      Horse Shows Association, the Federation Equestre Internationale, and the
      Association of Racing Commissioners International, Inc, in the policing of drug
      use in horses competing in events under their control.

PMID- 8299008
TI  - Repression of cytochrome P450 by cytokines: IL-1 beta counteracts clofibric acid
      induction of CYP4A in cultured fetal rat hepatocytes.
AB  - Interleukin-1 is known to repress a number of hepatic drug-metabolizing enzymes
      in rats and humans. The effect of interleukin-1 beta on lauric acid 12
      hydroxylase (CYP4A family) was studied in cultured fetal rat hepatocytes after
      clofibric acid induction. Dexamethasone was used as an agent promoting
      differentiation and long-term maintenance of active hepatocytes. Dexamethasone
      and clofibric acid in combination allowed maximal (13.5-fold) induction of
      CYP4A1. Lauric acid 12-hydroxylase activity was found to increase with time in
      culture. Interleukin-1 beta adversely affected P4504A clofibric acid-induced
      activity, totally eliminating the effect of induction at doses exceeding 5 ng/ml.
      This repression/inhibition was dose-dependent. The mechanism by which interleukin
      1 beta prevents the development of cytochrome P4504A activity is unclear.

PMID- 8299010
TI  - Factors affecting drug withholding time estimates in horses.
AB  - Although all the factors discussed in this article may have an effect on drug
      withholding time estimates, the factors that have the potential for the greatest
      effect or that have been found to cause positive tests in the past are 1. Dosage:
      Increasing the drug dosage will require a longer withholding time. 2. Dosing
      interval: Narrowing the dosing interval will require a longer withholding time.
      3. Administration route: In general, oral administration results in lower peak
      plasma concentrations but may result in longer excretion in the urine and
      therefore longer withholding time. 4. Drug interaction: The co-administration of
      drugs may result in interference with the clearance of either drug requiring
      longer withholding times. It should be noted that environmental chemicals,
      natural substances in feeds, and other substances have the potential to alter the
      rate of elimination of a drug. 5. Exercise: Exercise may have a significant
      effect on the excretion of a drug or its metabolites in the urine. The magnitude
      of this effect is primarily dependent on the nature of the drug and the
      mechanisms involved in the renal excretion of the drug. These effects may be
      important if experimental studies in resting horses are used to estimate
      withholding times. 6. Analytic method: A change in a screening test for a
      therapeutic medication by the laboratory may dramatically increase the
      withholding time for that drug. Veterinarians need to work closely with racing
      commissions and horse show associations to encourage them to provide advanced
      notice of such changes and to provide revised withholding time estimates. The
      attending veterinarian should explain the caveats of withholding time estimates
      to the trainer or owner to avoid misunderstandings in the event of a positive
      test. However, the decision to enter the horse in competition after drug
      treatment is ultimately the responsibility of the trainer and owner.

PMID- 8299011
TI  - Pharmacokinetic values of drugs frequently used in performance horses.
AB  - Tables of values of pharmacokinetic variables (volume of distribution, total body
      clearance, and plasma elimination half-life) of drugs frequently administered to
      performance horses are accompanied by explanatory notes. Drugs described include
      the nonsteroidal anti-inflammatory drugs, corticosteroids, anabolic steroids,
      central nervous system-modifying drugs, respiratory system drugs, diuretics,
      local anesthetics, and antibacterial drugs.

PMID- 8299012
TI  - Assessment of drug effects on performance.
AB  - Few definitive studies have been performed that unequivocally demonstrate the
      ability of a drug to alter the performance of a horse. Nonetheless, the use of
      drugs in competing horses is regulated worldwide. Drugs have been categorized
      according to their abuse potential. However, there is still some confusion over
      what is meant by the terms "performance" and "drug." In the racing community,
      performance means speed, and fatigue and pain are among its greatest detractors.
      Speed is most appropriately measured on the racetrack. There are a multiplicity
      of internal and external variables that influence a horse's racetrack
      performance. Consequently, it is difficult to show drug-induced changes in speed,
      experimentally, on the racetrack. However; rigorous experimental designs and
      larger numbers of horses may enhance the value of this approach. High-speed
      equine treadmills provide a modified racing laboratory environment. A number of
      performance-related variables such as heart rate, oxygen consumption, and lactate
      production can be measured, and correlations with actual performance times have
      been shown. Drug-induced changes in some of these variables have been
      demonstrated. Behavioral pharmacology techniques have been adapted to the horse.
      Finite changes in spontaneous locomotor activity and pain perception have been
      demonstrated following the administration of putative stimulants, depressants,
      and anesthetics. Precise onset, duration of action, and potency of the various
      agents can be determined using this approach. Drug-induced changes in heart and
      respiratory rates in laboratory horses at rest also may be of some predictive
      value. Retrospective studies of racing times in medicated horses have yielded
      some interesting results. At the present time, the regulatory science of "doping
      control" is still heavily reliant on inference and extrapolated knowledge of
      human and equine pharmacology.

PMID- 8299013
TI  - Furosemide, bumetanide, and ethacrynic acid.
AB  - Furosemide and, less commonly, bumetanide and ethacrynic acid are potent
      diuretics administered to horses for a variety of reasons, including prophylaxis
      of exercise-induced pulmonary hemorrhage. These drugs affect urine volume and
      composition, and furosemide has marked effects on plasma volume and composition
      and on systemic hemodynamics at rest and during exercise.

PMID- 8299014
TI  - Nonsteroidal anti-inflammatory drugs.
AB  - NSAIDs' mechanism of action by inhibiting the synthesis of prostanoids accounts
      for both their therapeutic and toxic effects. They are commonly used in acute and
      chronic musculoskeletal and soft-tissue conditions. Adverse reactions include
      gastrointestinal disturbances and hypoproteinemia. Their pharmacologic effect
      seems to have a longer duration than their plasma concentrations indicate. This
      gives implications on current regulations for competing horses and the relevance
      of permitted levels has been questioned. The NSAIDs do not appear to enhance
      performance, but rather allow the horse to run up to its potential by reducing
      pain and lameness. There is concern over the possible hazards to the horse by
      this kind of therapeutic use. In conclusion, NSAIDs have well justifiable
      therapeutic uses in equine practice. They should, however, be used when there is
      a clear clinical indication, in safe dose rates and without jeopardizing the
      welfare of the performance horse.

PMID- 8299015
TI  - Clinical use and characteristics of the corticosteroids.
AB  - Corticosteroids possess potent anti-inflammatory activity and are commonly
      injected intra-articularly for local relief of inflammatory lesions in
      performance horses. However, the suppression of anabolic activity in the joint
      may lead to an increased rate of joint breakdown. Complications associated with
      intra-articular corticosteroid therapy include septic arthritis, which is usually
      due to inadvertent joint contamination at the time of corticosteroid injection,
      and steroid arthropathy, which is characterized by an accelerated rate of joint
      destruction and radiographic evidence of severe degenerative joint disease.
      Prognosis for both of these conditions is poor. Adverse effects of systemic
      corticosteroid therapy includes suppression of the hypothalamic-pituitary adrenal
      system, increased susceptibility to infection, and laminitis; however, moderate
      use of glucocorticoids does not permanently affect adrenal function.

PMID- 8299016
TI  - Anabolic steroids.
AB  - Anabolic steroids have been employed extensively in equine practice over the past
      25 years. Their usefulness is largely dependent on subjective opinions, as only
      minimal studies have been carried out in horses. Therefore, their use will vary
      markedly between practitioners depending on their personal experiences and
      pressures by trainers to use them. They form part of rational therapy in a
      variety of conditions. In addition to use for increasing muscle mass, they are
      used to a varying extent in the raising of yearlings and in the training and
      racing of horses with the view of improving performance. However, in almost all
      countries, the latter use is largely curtailed, and the presence of these
      substances in postrace urine samples constitutes use of an illegal substance. To
      detect the use of anabolic steroids, including testosterone, sensitive ELISA
      tests for screening and GC/MS for confirmation have been developed. These
      compounds can be used safely. Risks can be encountered if too high doses are
      used, as horses may become difficult to manage due to increased aggressiveness
      and other stallion-like behavior. Reproductive efficiency in both stallions and
      mares may be temporarily impaired, but this is quite rapidly reversible following
      cessation of treatment.

PMID- 8299018
TI  - Narcotics and local anesthetics.
AB  - The recognition and alleviation of animal pain is a growing veterinary and public
      concern. Pain can be of an acute or chronic nature with different behavioral
      manifestations. Physiologically, pain is a dynamic and complex phenomenon that
      produces changes in the central and autonomic nervous systems as well as in the
      endocrine system. Horses and other animals appear to possess an endogenous pain
      suppressing system involving the brainstem and spinal cord. This system can
      modulate pain perception and the responses to it. The recently discovered
      endogenous opioid peptides (endorphins and enkephalins) appear to play a role in
      this system, which is activated by stress. Opioids (narcotic analgesics) act to
      selectively depress pain-sensitive cells. Opioid analgesics may act via multiple
      opioid receptors. Each subclass of opioid receptor has a different pharmacologic
      profile. Classical opioids that act at mu (morphine) receptors typically produce
      analgesia, increased locomotor activity, cardiorespiratory stimulation, and a
      decrease in intestinal peristalsis in the horse. Opioids that act at kappa
      receptors produce analgesia, sedation, ataxia, and minimal autonomic effects in
      the horse. Owing to their lack of excitatory actions, the kappa opioids represent
      a potentially useful class of analgesics for use in equine species. Local
      anesthetics depress all excitable cells and can diminish sensory, motor, and
      muscular function. They do not act selectively on pain fibers, although pain is
      among the first sensations lost following a nerve block. Local anesthetic
      activity is enhanced by increased extraneuronal pH, nerve cooling, increased
      nervous activity, coadministration of a vasoconstrictor or hyaluronidase, delayed
      systemic absorption, prolonged drug metabolism, and by using agents with high
      lipid solubility. Procaine, lidocaine, and mepivacaine are among the most widely
      used and studied agents in horses. These agents and/or their metabolites can be
      readily detected in urine; in some cases, for prolonged periods.

PMID- 8299017
TI  - Fluids, electrolytes, and bicarbonate.
AB  - In an attempt to enhance performance, primarily by delaying the onset of fatigue,
      a variety of formulations of fluids, electrolytes, and sodium bicarbonate are
      administered to performance horses. Some current practices of fluid and
      electrolyte supplementation are well justified; others have no basis to support
      their use. In addition, occasional combined administration of certain agents
      (i.e., furosemide and sodium bicarbonate) can have detrimental effects on
      performance.

PMID- 8299019
TI  - Effects of sympathomimetic and sympatholytic drugs on exercise performance.
AB  - This article has presented information on the importance of the sympathetic
      nervous system in the response to exercise. The authors have reviewed the very
      limited information on the effects of sympathomimetic and sympatholytic drugs on
      exercise performance in the horse. Most of these drugs are specifically
      prohibited under the rules of racing, and they have significant side effects that
      either decrease performance or make their use dangerous to both the horse and
      horse-man. Additionally, all of these drugs or their metabolites are readily
      detected by current drug testing protocols. Further information is needed to
      expand our knowledge of how each of these substances affects the health of the
      equine athlete.

PMID- 8299020
TI  - Drugs affecting the hematologic system of the performance horse.
AB  - Pharmacologic alterations in the hematologic and rheologic properties of blood
      may have an important effect on transport and delivery of oxygen to working
      muscle during exercise. This article briefly reviews erythropoiesis, hematologic
      and rheologic responses to training and exercise, and the influence of these
      alterations on exercise performance. The hemorrheologic and performance effects
      of hematinics, hematopoietic stimulants, and alterations in blood rheology are
      discussed. The effects of exercise on blood coagulation, fibrinolysis and
      platelet function, and the effects of drugs that alter platelet function are
      briefly described.

PMID- 8299021
TI  - Behind the scenes of hospital restructuring: management consultants profit off RN
      layoffs.

PMID- 8299022
TI  - Encopresis: developmental, behavioral and physiological considerations for
      treatment (continuing education credit).

PMID- 8299023
TI  - Juvenile and adult dermatomyositis among the Chinese: a comparative study.
AB  - Between 1983 and 1992, 11 children and 38 adults were seen at Taichung Veterans
      General Hospital with a definite diagnosis of dermatomyositis. Their clinical
      pictures, laboratory findings, courses and outcomes were compared. The mean age
      at diagnosis was 12 years and 50 years, respectively. Children had a higher
      female-to-male ratio (2.7:1 vs. 1.2:1) and a more acute onset, while adults had a
      higher incidence of malignancy and other connective tissue disease associations.
      Clinically, shawl sign was more common in the adults, whereas myalgia was more
      frequently seen in the children (0.05 < p < 0.1). Hemograms, serological
      parameters and immunological investigations showed no significant differences
      between the two groups. Elevated erythrocyte sedimentation rate and circulating
      immune complexes were found in over half of both groups of patients; however,
      their values bore no relationship to either disease activity or future outcome.
      Although no significant differences were demonstrated between the two groups of
      patients with regard to either clinical manifestations or laboratory findings,
      the disease entity seemed not to be the same because evidence of vasculopathy in
      muscle pathology was more prominent in the children, with endothelial swelling
      and necrosis the most common findings. Steroids had been used as the first choice
      of therapy in both groups of patients, followed by cytotoxic drugs and
      immunosuppressants. Children had a more favorable outcome compared to a 24%
      mortality rate in the adult group. Experience here recommends a complete cancer
      work-up in adults, especially for nasopharyngeal carcinoma among the Chinese.
      Various autoantibodies screenings may also be helpful for early detection of
      other associated connective tissue diseases.

PMID- 8299024
TI  - Nerve conduction studies in healthy Chinese: correlation with age, sex, height
      and skin temperature.
AB  - We consecutively collected 68 normal subjects who assented to receive
      electrophysiological examination in four limbs. There were 50 men and 18 women,
      with a mean age of 50.8 +/- 17.9 years (range: 15-88) and a mean height of 162.72
      +/- 9.05 cm (range: 138-180). Mean skin temperature was 32.75 +/- 1.51 degrees C
      (range: 29.4-35.6) at wrist and 30.9 +/- 1.1 degrees C (range: 29-33) at lower
      leg. The mean values with standard deviation of the nerve conduction parameters
      such as distal latency, nerve conduction velocity, amplitude, duration and area
      of compound muscle action potential and sensory action potential, minimal
      latencies of H reflexes and F responses, and their side-to-side differences were
      presented. Age was negatively correlated with motor nerve conduction velocity (P
      < 0.05, r = -0.37 to -0.46), amplitude of compound muscle action potential (P <
      0.05, r = -0.32 to -0.43) and sensory action potential (P < 0.05, r = -0.33 to 
      0.65), but not with sensory nerve conduction velocity (P > 0.05). Height was
      correlated with minimal latencies of H-reflexes and F-responses (P < 0.05, r =
      0.45 to 0.76). Gender and temperature were not correlated with any parameters (P
      > 0.05).

PMID- 8299025
TI  - The effect of tissue plasminogen activator (t-PA) on cerebral vasospasm in canine
      subarachnoid hemorrhage.
AB  - Cerebral vasospasm is a serious complication of subarachnoid hemorrhage following
      rupture of intracranial aneurysm. It always leads to grave neurological deficit
      and sometimes causes mortality of the patient. Many neurosurgeons consider it as
      a result of the presence of subarachnoid blood clot and try to prevent it by
      evacuating the blood clot immediately after clipping of the ruptured aneurysm
      during operation at acute stage. A nonmechanical method of clearing blood clot by
      intrathecal injection of thrombolytic agents has been used in recent years.
      Tissue plasminogen activator (t-PA) is one of these new drugs. Twenty-two dogs
      were divided into 4 groups in this study: control group (n = 6), vehicle group (n
      = 6), 50 micrograms/kg t-PA treated group (n = 5) and 100 micrograms/kg t-PA
      treated group (n = 5). These dogs were prepared as "double hemorrhage canine
      model." Vehicle solution or different dosages of t-PA were given twice into the
      foramen magnum through an anchored catheter after artificial subarachnoid
      hemorrhage. The results showed that the ratio of diameter of basilar artery
      measured after treatment to that measured before treatment in each groups were 75
      +/- 8%, 72 +/- 4%, 86 +/- 4%, and 87 +/- 4%, respectively. The differences
      between control group and either 50 micrograms/kg t-PA treated group or 100
      micrograms/kg t-PA treated groups were statistically significant (p < 0.05). It
      is concluded that effective prevention of cerebral vasospasm can be achieved
      safely by administration of t-PA as low as 50 micrograms/kg for two divided doses
      to dissolve the subarachnoid blood clot in canine model.

PMID- 8299026
TI  - A clinical and MRI study of cerebellar infarctions.
AB  - The frequency of cerebellar infarctions over two and a half years was 2.7% of the
      1300 hospitalized patients over that period. Sixteen patients with cerebellar
      infarctions were studied by using clinical manifestations and magnetic resonance
      imaging (MRI). Ages ranged from 41-87 (mean 63.5) years; 13 were men and 3,
      women. Risk factors included: hypertension (50%), diabetes (44%), prior stroke
      (44%), cardiac disease (38%), and hyperlipidemia (19%). Common symptoms and signs
      were dizziness/vertigo (75%), unsteadiness (69%), dysarthria (69%), and
      nausea/vomiting (50%). Infarcts mainly involved the posterior inferior cerebellar
      artery (PICA) territory and tended to be associated with brainstem infarcts in 14
      of the 16 patients. Most cerebellar infarctions had a benign course, especially
      the small ones. No mortality was noted in this series. The short-term outcome of
      the cerebellar infarctions seemed to depend on the size of the infarcts and the
      sites of the artery occlusion. It was concluded that diagnosis of cerebellar
      infarctions requires a high index of clinical suspicion, especially when patients
      present with a sudden onset of ataxia, dizziness/vertigo, nausea/vomiting and
      dysarthria; and that MRI is a useful tool for the detailed study of cerebellar
      infarctions and can elucidate associated brainstem infarcts.

PMID- 8299027
TI  - The causes of ischemic stroke in patients under 45 years of age.
AB  - From November 1982 to June 1991, a total of 81 cases of ischemic stroke in
      persons under 45 years of age were analyzed retrospectively. There were 44 males
      and 37 females, aged from 2 to 45 years (average 34.6 years). The modes of onset
      were immediately completed in 55 cases, progressed over a period of 1 hour to 5
      days in 23 cases, and fluctuated over a period of 1 to 2 days in 3 cases. Fifty
      six cases had one stroke episode; the others had transient ischemic attack or/and
      several episodes of cerebral infarction. Sixty-five cases had symptoms arising
      from the region of the carotid artery, more than 3.4 times those arising from the
      basilar artery territory. Probable causes of stroke were atherosclerosis (54.3%),
      embolism (28.5%), arteropathy (8.6%), hematological disease and coagulopathy
      (3.7%) and undetermined (4.9%).

PMID- 8299028
TI  - [Transtympanic electrocochleography in Meniere's disease].
AB  - In order to examine the usefulness of the electrocochleography (ECoG) in the
      diagnosis of Meniere's disease and establish the diagnostic criteria in Chinese,
      transtympanic ECoG was performed on 18 normal ears, 22 Meniere's ears and 14 ears
      with cochlear type sensorineural hearing loss other than Meniere's disease.
      Although the Meniere's ears had larger mean summating potential (SP) than the
      normal ears, the difference between both groups was not statistically
      significant. The mean amplitude and latency of the action potential (AP) in
      Meniere's ears decreased and elongated significantly, but neither was sensitive
      enough in diagnosing Meniere's disease. The SP/AP amplitude ratio not only made
      significant difference among 3 groups, but also had good diagnostic sensitivity
      (59.1%) and specificity (92%) in diagnosing Meniere's disease while using the 95%
      upper confidence limit of the normative data (i.e., 34%). The SP/AP amplitude
      ratio of Meniere's ears tended to increase while the mean hearing level of 4-8
      KHz deteriorated. Also, abnormal enlargement of the SP/AP amplitude ratio in
      Meniere's disease tended to be the result of decreased AP amplitude.

PMID- 8299029
TI  - [The immediate interpretation for fine-needle aspiration cytology].
AB  - From December 1990 to November 1992, 2005 cases of immediate interpretation for
      fine-needle aspiration (FNA) cytology were performed, of which 727 cases were
      confirmed by surgical pathology. A mobile cytologic laboratory (a cart loaded
      with a dual viewing microscope, Liu's staining solutions, hair dryer, and slides)
      can be moved to the Out-patient Department, wards and Computed Tomography room,
      where clinicians perform aspiration and pathologists read smears. Immediate
      verbal diagnoses are documented to patients' charts and listed in cytopathologic
      files. Immediate interpretation in this entire series yielded a sensitivity
      92.5%; specificity, 98.1%; false-positive rate, 1.1%; false-negative rate, 3.2%;
      positive predictive value (PV), 97.3%; negative PV, 94.7% and efficiency, 95.7%.
      The cause of false-negative results in the 23 cases probably came from the
      hesitation in making an immediate diagnosis. Most of these cases were malignant
      lymphoma or breast carcinoma. The roles of immediate cytodiagnosis are (1) to
      decrease the inadequate rate of FNA specimens; (2) to render preliminary
      diagnosis for clinicians to make decisions; (3) to provide on-site teaching
      material for both clinicians and pathology residents to better understand
      clinicopathological correlations; (4) to act as the initial diagnostic procedure
      in the evaluation of a superficial palpable mass. This study shows that immediate
      interpretation for FNA cytology is a simple, rapid, accurate and noninvasive
      diagnostic procedure that can be routinely used for superficial palpable masses.

PMID- 8299030
TI  - [Detection of Mycobacterium tuberculosis in sputum by polymerase chain reaction].
AB  - A method based on DNA amplification (PCR) and hybridization for the detection of
      M. tuberculosis was used to test 86 sputum specimens from 52 patients in whom
      tuberculosis was suspected. M. tuberculosis was detected in 35 specimens, with 1
      false positive. The finding was negative in 51 specimens, of which 4 were false
      negative. Thirty-two specimens were positive by standard microbiological criteria
      (acid-fast stain and culture), and 54 specimens were negative (including 6 false
      negative). Of 38 specimens with definite diagnosis of tuberculosis, 89.5% (34/38)
      were positive by DNA amplification and 84.2% (32/38) by acid-fast stain and/or
      culture. The difference is not statistically significant (P > 0.05). The
      specificity was 97.9% (47/48) and 100% (48/48) by DNA amplification and acid-fast
      stain and/or culture, specificity was 97.9% (47/48) and 100% (48/48) by DNA
      amplification and acid-fast stain and/or culture, individually, and difference is
      also not statistically significant (P > 0.05). However, PCR combined with
      specific DNA probe is more sensitive than the acid-fast stain method and faster
      than the culture method. Therefore it is useful for early detection of pulmonary
      mycobacterial infection.

PMID- 8299031
TI  - Melkersson-Rosenthal syndrome: a case report.
AB  - The Melkersson-Rosenthal syndrome (MRS) is a rare disease which includes a triad
      of orofacial swelling, recurrent facial nerve paralysis and plicated tongue. MRS
      can still be diagnosed when any two of the conditions are present. Because of its
      rarity, it is usually ignored and misdiagnosed. Herein, a diabetic female patient
      with this syndrome, previously diagnosed as Bell's palsy, is described. This case
      report is presented to encourage awareness of this entity among medical
      practitioners. In addition, the MRS literature is reviewed with respect to
      incidence, etiology, clinical features, pathology, differential diagnosis and
      treatment.

PMID- 8299032
TI  - Joubert syndrome in Chinese infants and children: a report of four cases.
AB  - Four Chinese infants and children (3 females & 1 male), aged from five months to
      three years, are diagnosed with Joubert syndrome by clinical and radiological
      findings. The clinical presentations included panting respiration with apnea in
      the newborn period (4/4), psychomotor retardation (4/4) and ataxia (2/4). The
      ocular findings were strabismus (3/4), unilateral ptosis (2/4), jerky eye
      movement (1/4) and retinal atrophy (1/4). Associated cerebral anomalies were
      occipital encephalocele (1/4) and hypoplasia of corpus callosum (1/4). All four
      underwent electroencephalography, abdominal ultrasonography, auditory and visual
      evoked potential tests; results were all normal. Two patients underwent
      electroretinogram with normal findings. The brain magnetic resonance imagings of
      all four patients showed dysgenesis of cerebellar vermis. For children presenting
      with ataxia and psychomotor retardation, Joubert syndrome is a more obvious
      diagnostic choice, but it is also important to keep this unusual disorder in mind
      as a differential diagnosis of neonatal tachypnea with apnea.

PMID- 8299033
TI  - Multiple glomus tumors: a case report.
AB  - Multiple glomus tumor (MGT) is rare in incidence. A 37-year-old male was
      diagnosed to have localized MGT over his right leg. With the characteristics of
      unusual location (right lower leg), development in sequence, and distribution
      along the course of the lateral sural cutaneous nerve. Its pathological findings
      were also characteristic. When the overall presentations showed in cases with
      recurrent symptoms and signs of glomus tumor after surgical excision, recurrence
      and multiplicity should be considered.

PMID- 8299034
TI  - Septicemia caused by Vibrio parahemolyticus: a case report.
AB  - Vibrio parahemolyticus is a halophilic marine vibrio commonly associated with
      outbreaks of acute gastroenteritis which also sometimes causes serious wound
      infection. It is an uncommon cause of septicemia. A few reports suggest that
      patients with chronic liver disease and leukemia are more susceptible. A case of
      liver cirrhosis with septicemia caused by this organism is discussed. The
      patient's condition rapidly deteriorated, and he died 12 hours after admission.

PMID- 8299035
TI  - Histometric analysis of cell populations in gingiva with bleeding on probing by
      immunohistochemistry.
AB  - The present study was performed by immunohistochemical methods in order to
      morphometrically characterize and compare the composition of cellular infiltrates
      in human gingivae with bleeding and non-bleeding upon probing. A total of 64
      gingival biopsies (33 bleeding and 31 non-bleeding gingivae) were obtained from
      23 patients. Routine Hematoxylin & Eosin and immunohistochemical stains were
      performed following tissue preparations. On each section, three zones were
      histologically divided. For each zone, the percentage and histometric analysis of
      plasma cells, phagocytic cells, B-cells and T-cells was calculated to
      characterize the composition of cellular infiltrates in gingiva associated with
      bleeding on probing. Significant difference was found in the middle and apical
      zones of infiltrated connective tissue when compared with plasma cells expressed
      by kappa- or lambda-chain positive immunostaining between bleeding and non
      bleeding gingivae. Significant difference was also found in the coronal zone when
      compared with phagocytic cells and B lymphocytes between bleeding and non
      bleeding gingivae. It is suggested that clinical bleeding tendency of gingiva may
      be highly associated with histological alterations of underlying inflammatory
      cell populations and a complicated immunological mechanism appears to be
      involved.

PMID- 8299036
TI  - Role of MR imaging of middle third esophageal carcinoma in determining
      resectability.
AB  - Twenty-one patients with middle third esophageal carcinoma were prospectively
      evaluated by magnetic resonance imaging (MRI) to determine the resectability of
      the primary tumor. For 8 of the 21 patients, contrast medium was administered
      during the procedure. Evidences of aortic or tracheobronchial invasion shown on
      MRI were compared with surgico-pathologic findings, as well as mediastinal
      lymphadenopathy. Eleven patients (52%) had proved unresectable tumors (three
      cases of aortic invasion, five cases of tracheobronchial invasion and three cases
      of combined aortic and tracheobronchial invasion). In all eleven cases, these
      features were correctly detected by MRI. Two patients had false-positive findings
      on MRI. No patient had false-negative results. The sensitivity, specificity and
      accuracy were 100%, 80%, and 90% for MRI. Unsatisfactory results were obtained in
      evaluation of regional lymph node metastasis. Only two tumors in eight patients
      had good enhancement after contrast medium was given. We conclude MRI had a high
      accuracy in predicting resectability of tumors in patients with esophageal
      carcinoma.

PMID- 8299037
TI  - The efficacy of intranasal DDAVP therapy in children with nocturnal enuresis.
AB  - This prospective self-controlled study was designed to evaluate the safety and
      efficacy of Desmopressin (DDAVP) in the treatment of childhood primary nocturnal
      enuresis (PNE) and the diurnal variation of ADH secretion and urine
      excretion/concentration in these children. Twenty-three children (15M,8F), aged 5
      16 years, who wet their beds at least 3 nights per week were enrolled in the
      study. After a four-week observation period, they were hospitalized for one day
      to monitor intake, output, renal sonography, plasma ADH, urine and serum
      osmolality. Intranasal DDAVP treatment at a dose of 15-30 micrograms at bedtime
      was started with a 4-week titration period followed by a 3 to 6-month full dose
      treatment period. Subsequently the dose was tapered off for one to two months,
      and the patients were followed for at least two months to observe any recurrence.
      The results showed no diurnal difference of ADH level in these children (p >
      0.05); serum osmolality decreased slightly during sleep (p < 0.01); urine
      production decreased, and urine osmolality increased, during sleep. Seventeen
      children (81%) responded with a more than 50% reduction in frequency of enuresis:
      11 were excellent responders, 6 were partial responders, while 4 failed. After
      completion of therapy, four (19%) remained dry and were considered cured; the
      rest had much less frequent recurrence. There were no subjective complaints other
      than mild local discomfort; laboratory test results remained normal. It was
      concluded that intranasal DDAVP is a safe and effective treatment for PNE which
      usually works promptly. Given the spontaneous annual remission rate of 14%, the
      cure rate of 19% in this study was not satisfactory.

PMID- 8299038
TI  - Articular manifestations of renal osteodystrophy.
AB  - The relationship between hyperparathyroid bone disorders and chronic renal
      diseases has been studied extensively for a long period of time. Zvaifler and
      Bywaters are the first to emphasize articular manifestations in
      hyperparathyroidism. Sundaram has found 30% in 80 hemodialysis patients
      presenting with articular disorders in hands. We reviewed routine radiographs of
      258 uremia patients retrospectively and found that 36 patients had typical X-ray
      presentations of renal osteodystrophy. Sixteen among them (44.44%) were noted
      with articular involvement. Fourteen patients involved axial joints including
      sacroiliac, acromio-clavicular, sternoclavicular and symphysis pubis in
      decreasing order. Appendicular joints involvement were found in 6 patients,
      patellofemoral joints and small joints of hands involvement in 4 patients
      respectively and hip and shoulder joints in each one patient. None of the 16
      patients complained joint pain. Diagnosis is easy because of the uncommon
      presentations of joint disorders in uremic patients. However, more knowledge
      about articular manifestations of renal osteodystrophy may eliminate the
      unnecessary investigations.

PMID- 8299039
TI  - Pseudomonas septicemia in infants and children: a retrospective analysis of 49
      cases.
AB  - Reviewed 49 cases of Pseudomonas bacteremia which occurred in pediatric patients
      during an 8-year period showed the annual rate, per 1000 discharges, was 1.7. In
      most of the patients (73.5%), the disease was hospital-acquired. Male to female
      distribution was about 3 to 2. The average age of the 49 patients was 1.29 years,
      and 55.1% were infected at less than 2 months old. Overall mortality was 44.9%;
      among the mortalities, 63.6% were under two months of age. Clinical features were
      not characteristic, but the most common sign associated with this infection was
      fever (42.9%). Ecthyma gangrenosum occurred in only one patient. Respiratory
      tract and skin were the most frequent sources of the bacteremia. Polymicrobial
      bacteremia occurred in 18.4%. Patients with shock, pneumonia, inadequate
      antibiotic therapy or persistent neutropenia had a substantially poorer
      prognosis. Administration of combination therapy to patients with Pseudomonas
      bacteremia seemed to be superior to monotherapy for positive outcome.

PMID- 8299040
TI  - Emergency department recognition of pulmonary embolism.
AB  - The cases of forty-six patients who were admitted via the Emergency Department
      (ED) with suspected pulmonary embolism (PE), during a ten-year period, were
      reviewed. Ventilation perfusion lung scans were done in all patients, and
      pulmonary angiography was performed in 26. Thirty-six PE patients (78%) were
      correctly diagnosed by emergency physicians. Ten patients (22%) were erroneously
      diagnosed at the ED but were proved otherwise after hospitalization. The average
      age of the patients was 54 years, with males dominantly 67%. Overall mortality
      rate was 8.7%. Predisposing risk factors for PE were documented in 20 patients
      (43%). Prior history of thrombophlebitis (17%) or pulmonary embolism (13%), and
      immobilization (13%) were significant. The most common clinical features were
      dyspnea (76%), pleuritic pain (74%) and hemoptysis (41%). Thirty patients (65%)
      had tachypnea and 20 patients (43%) had tachycardia. Chest radiographs were
      abnormal in 35 cases (76%), and abnormal ECG findings were noted in 27 patients
      (59%). However, these abnormalities of chest radiographs or ECG were not
      sufficiently specific to confirm or exclude the diagnosis of PE. Noninvasive or
      contrast venography for deep vein thrombosis were performed in 31 patients (67%),
      of whom 17 cases (37%) had positive results. All patient received anticoagulation
      treatment. And six patients had thrombolytic agents as well.

PMID- 8299041
TI  - Central nervous system tuberculosis in infants and children.
AB  - Hospital records of 16 infants and children (9 males & 7 females) with
      tuberculous meningitis or tuberculoma were reviewed retrospectively over a 10
      year period. Patients were aged from 5 months to 16 years, with a mean age of 7.2
      years. The diagnoses were confirmed via a positive culture for Mycobacterium
      tuberculosis from cerebrospinal fluid (CSF) in 14 patients, and from brain tissue
      in 2. Most patients presented with fever (100%), conscious change (80%), vomiting
      (80%) and headaches (75%). Neurologically, meningeal and pyramidal signs were the
      most common findings. Lymphocytic CSF pleocytosis with hypoglycorrhachia,
      increased protein, and decreased CSF/serum glucose ratio were the major CSF
      findings in our patients. Hyponatremia was present in 70%. Brain computerized
      tomography showed hydrocephalus (87%), basal exudate (50%), ischemic infarction
      (37%) and tuberculoma (12%). Two patients (12%) expired and 10 (71%) of the
      surviving patients had neurological sequelae. In summary, the characteristic CSF
      findings and hydrocephalus (87%) seemed to be sensitive clues supporting early
      initiation of antituberculous drug therapy and thorough investigation as
      reflected in this series.

PMID- 8299042
TI  - [Total intravenous anesthesia with O2 mask in transthoracic endoscopic
      sympathectomy for palmar hyperhidrosis].
AB  - Using non-invasive monitors (such as blood pressure, O2 saturation, end-tidal CO2
      pressure monitors and electrocardiograms), the application of total intravenous
      anesthesia with O2 mask in transthoracic endoscopic sympathectomy was evaluated.
      A total of 198 palmar hyperhidrosis patients were studied. In the study, the
      durations of surgery were 5-15 min (mean 8 min) with anesthesia duration of 8-20
      min (mean 12 min), respectively. The cardiovascular system was quite stable
      during operation, with systolic blood pressures of 90-165 mmHg (mean 132 mmHg),
      diastolic blood pressures of 50-106 mmHg (mean 92 mmHg) and heart rates of 56-130
      beats/min (mean 104 beats/min). The respiratory function was maintained within a
      safety range with O2 saturation of 95-100% (mean 99%) and end-tidal CO2 pressure
      of 32-40 mmHg (mean 36 mmHg). After surgery, the major discomfort was chest pain
      (132/198), but this could be improved with intravenous analgesics. Patients'
      consciousness returned within 1-3 min. After ensuring their general condition was
      stable, patients were discharged within 24 hr. Preliminary study showed that
      total intravenous anesthesia plus muscle relaxant, with O2 mask and assisted
      ventilation, could serve as a safe and simple anesthesia for palmar hyperhidrosis
      patients who received transthoracic endoscopic sympathectomy.

PMID- 8299043
TI  - Gadolinium-DTPA enhanced magnetic resonance imaging of dural sinus occlusion in
      dural arteriovenous malformation: a case report.
AB  - A case of dural arteriovenous malformation of the transverse sinus, is presented,
      with dural sinus occlusion imaged with gadolinium diethylenetriamine pentaacetic
      acid (Gd-DTPA). The patient, a 59-year-old man, had developed easy forgetfulness
      and frequent misreading over a four-month period; he had had episodic vertiginous
      attacks since 3 January 1992. Magnetic resonance (MR) imaging done on 21 January
      1992 showed abnormally dilated subcortical vessels and a non-hemorrhagic venous
      ischemia in the subcortical white matter of the left posterior temporal lobe.
      Thrombosis of the left sigmoid sinus was seen. After administration of
      intravenous Gd-DTPA, dense enhancement in the left sigmoid sinus and abnormal
      serpiginous enhancement in the left temporal lobe were revealed. Left carotid
      angiography showed dural arteriovenous malformation in the posterior fossa, with
      non-opacification of the left transverse and sigmoid sinuses, plus forward venous
      drainage into left superior petrosal sinus. The focal neurologic deficits in this
      case from non-hemorrhagic venous ischemia in the subcortical white matter of the
      left posterior temporal lobe, and were secondary to venous hypertension.

PMID- 8299044
TI  - Acute lobar nephronia: a case report.
AB  - Acute lobar nephronia (ALN), a term analogous to acute lobar pneumonia, refers to
      a renal mass caused by acute focal infection without liquefaction. An alternative
      term is acute focal bacterial nephritis (AFBN). Fever, flank pain or back pain
      are the most frequently encountered clinical characteristics. Imaging modalities
      used to establish a definite diagnosis of acute lobar nephronia included
      sonography, computed tomography and nuclear medicine. Uroradiographic findings in
      this condition can mimic a renal abscess or neoplasm. Further distinction between
      acute lobar nephronia and other renal masses is aided by the appropriate use of
      renal sonography and computerized tomography is the most effective and least
      costly method in diagnosis. Serial sonograms can be used to monitor response to
      antibiotic therapy. Clinical and uroradiographic characteristics of a six year
      old female patient with acute lobar nephronia are presented, along with a review
      of literature.

PMID- 8299045
TI  - Myokymia and neuromyotonia of the tongue: a case report of complication of
      irradiation.
AB  - A 51-year-old man has suffered from progressive dysarthria since 1989. He himself
      noted slight weakness and tightness of the tongue, so that he was unable to
      perform motor tasks in a normal fashion. He was diagnosed as having
      nasopharyngeal carcinoma and had irradiation 70 Gy in 32 divided doses in 1979.
      Neurological examination revealed left-sided tongue atrophy and myokymia sparing
      of facial muscles involvement. Electrical discharges of myokymia and
      neuromyotonia were observed in the tongue muscles, suggesting hypoglossal nerve
      lesion with hyperexcitability of the axon membrance. Computed tomogram of brain
      did not show any evidence of recurrence of tumor; indicating that irradiation was
      the pathologic basis. Our report revealed that myokymia and neuromyotonia of the
      tongue was an unusual complication of irradiation.

PMID- 8299046
TI  - Adult type squamous papillomatosis of larynx with extension to trachea and
      bronchial tree: a report of two cases.
AB  - We describe 2 rare cases of adult type squamous papillomatosis of larynx with
      spread to the trachea and bronchial tree that occurred at the age of 72 and 42,
      respectively. They were treated with laser therapy for laryngeal and tracheal
      lesions; the first case also received surgical resection. However, due to the
      extent of papilloma involvement, the outcomes were completely different between
      both. The first patient had all lesions successfully removed by combined surgical
      resection and laser photoresection, and the patient remained asymptomatic up to 7
      years after the operation. The second patient, however, had been bothered by
      recurrent tumors with associated repeated secondary infections, despite
      treatment, for 6 years and 3 months before his death.

PMID- 8299047
TI  - Intraocular pressure and glaucoma.

PMID- 8299048
TI  - Changing risk for early transplant failure: data from the Ontario Corneal
      Recipient Registry.
AB  - To examine the joint effects of donor, recipient and surgical characteristics on
      the risk of early corneal transplant failure, 73 cases of early failure (no
      period of clarity or clarity lasting no more than 28 days) reported to the
      Ontario Corneal Recipient Registry were compared with 1591 control transplants
      remaining clear for 6 months or more. In logistic regression models donor age was
      significantly associated with graft failure, with the odds of failure increasing
      by 24% per decade. In recipients with a history of cataract or glaucoma or with
      an intraocular lens in place the relative odds of failure ranged from 2.16 to
      3.08. Among surgical factors, larger grafts increased risk by 45% per 0.25 mm.
      Grafts received before 1987 had a consistently higher risk of early failure than
      those received in 1987 or later. Concurrent changes in storage media, handling of
      donor tissue and management of recipients may have been responsible. We conclude
      that donor, recipient and surgical factors all contribute to the risk of early
      transplant failure.

PMID- 8299049
TI  - Postoperative astigmatism following phacoemulsification with sutured vs.
      unsutured wounds.
AB  - A total of 293 cases of phacoemulsification cataract surgery with a 5.0- or 6.0
      mm frown incision were analysed retrospectively to compare postoperative
      astigmatism between cases with sutured wounds and those with unsutured wounds.
      Astigmatic analysis was done with a simplified method (keratometric readings with
      steep meridians between 46 degrees and 134 degrees were considered "with-the
      rule" [WTR], and those with steep meridians less than 46 degrees and greater than
      134 degrees, "against-the-rule" [ATR]). Among patients with WTR astigmatism
      preoperatively, the mean keratometric cylinder in the sutureless group (n = 53)
      was significantly lower at 1 day and at 4 to 6 months postoperatively than before
      surgery (p < or = 0.001); in the suture group (n = 120) the mean cylinder was
      significantly higher at 1 day and significantly lower at 4 to 6 months than
      before surgery (p < 0.05). Among patients with ATR astigmatism preoperatively,
      the mean keratometric cylinder in the sutureless group (n = 22) was significantly
      higher at 1 day than before surgery (p < 0.01); in the suture group (n = 98) the
      mean cylinder was significantly lower at 1 day than before surgery (p < 0.001),
      and the difference at 4 to 6 months almost reached statistical significance (p =
      0.052). Vector analysis showed that surgically induced cylinders in the suture
      and sutureless groups were similar. Our findings suggest that in the short term
      patients with preoperative WTR astigmatism may benefit from unsutured wounds, and
      those with preoperative ATR astigmatism may benefit from sutured wounds if the
      incision is placed in the vertical meridian.

PMID- 8299050
TI  - Incidence of accommodative impairment following traumatic hyphema.
AB  - To examine the effect of traumatic hyphema on accommodation, we reviewed the
      records of 158 patients (159 eyes) admitted to hospital between Jan. 1, 1988, and
      Dec. 31, 1989, for treatment of traumatic hyphema. A sample of 30 patients were
      examined an average of 29.6 months after injury, and 2 (7%) were found to have
      accommodative impairment of greater than 2.5 dioptres. Post-traumatic
      accommodative impairment may cause prolonged reading disability requiring
      asymmetric spectacle correction.

PMID- 8299051
TI  - Scheie's syndrome: the architecture of corneal collagen and distribution of
      corneal proteoglycans.
AB  - Processes that modulate the regular architecture and, hence, transparency of the
      cornea are poorly understood, although proteoglycans are thought to be involved.
      Scheie's syndrome displays corneal opacification and systemic accumulation of
      glycosaminoglycans. The manifestations of these two occurrences were examined in
      relation to the corneal stroma. Collagen architecture was investigated by
      transmission electron microscopy and synchroton x-ray diffraction. Cuprolinic
      blue staining located sulfated glycosaminoglycan deposits that disrupted the
      extracellular matrix. Unlike normal cornea, which contained collagen fibrils of
      remarkably uniform diameter (26.0 +/- 2.4 nm), there was a large range of fibril
      sizes in the Scheie's syndrome stroma (19.9 to 52.0 nm). Moreover, the
      distribution of fibril diameters appeared bimodal. X-ray diffraction confirmed
      the discovery of abnormally large stromal collagen. The results suggest a link in
      Scheie's syndrome between proteoglycan content/distribution and stromal
      disruption, and between stromal disruption and corneal opacification.

PMID- 8299052
TI  - Ultrasonography to assess patency of the tube in Molteno seton implantation.
AB  - It is occasionally difficult to ascertain postoperatively whether a Molteno
      implant is functioning or not. We have found that ultrasonography (B-scan) is a
      useful diagnostic tool in assessing tube patency. Polaroid images of 29
      ultrasound pictures, 8 with occluded tubes, were taken postoperatively and
      presented independently to a radiologist and a retinal specialist, who were asked
      to determine the functioning state of the Molteno implant. In all cases the
      observers were able to correctly identify whether the tube was patent or not.

PMID- 8299053
TI  - Bilateral penetrating keratoplasty and placement of a Molteno implant in a
      newborn with Peters' anomaly.

PMID- 8299054
TI  - Intraepithelial neoplasia of the cornea.

PMID- 8299055
TI  - Intraepithelial neoplasia of the bulbar conjunctiva clinically presenting as
      diffuse papillomatosis.

PMID- 8299057
TI  - The use of perfluorocarbon liquid in the surgical repair of stage 5 retinopathy
      of prematurity.

PMID- 8299056
TI  - Pneumocystis carinii choroidopathy and aerosolized pentamidine prophylaxis in a
      patient with AIDS.

PMID- 8299058
TI  - What have you done for me lately?

PMID- 8299059
TI  - Coordinating multidisciplinary, collaborative research: a formula for success.
AB  - Nursing continues to move toward the goal of providing care that is grounded in
      theory and research. As such, the CNS may perform the role of research nurse
      coordinator for collaborative research projects. In this article, three nursing
      principles that were successfully applied to the planning and conduct of
      multidisciplinary, collaborative research resulting in a high degree of
      participant satisfaction and subject retention are described. These three nursing
      principles are: (1) using the nursing process as an organizing framework for
      nursing practice, (2) delivering nursing care through a process of interpersonal
      relationships, and (3) allowing a humanistic philosophy to guide nursing actions.
      Knowledge and application of this "formula for success" will assist the CNS who
      is a novice at research to achieve a positive outcome in his or her endeavors.

PMID- 8299060
TI  - Image of nurse-midwifery: a barrier to practice.
AB  - The image of nurse-midwifery forms a barrier to utilization that is just as, if
      not more, formidable as laws restricting practice. In this paper, the issue of
      image for its impact on the practice of nurse-midwifery is analyzed. Historical,
      technological, consumer-oriented, and nursing-oriented factors that have affected
      midwifery's image and the profession's current status are explored.
      Recommendations to clarify the role and image, including political involvement,
      networking strategies, and research, are discussed. Although nurse-midwives, who
      emphasize cost-effective, quality, primary care, should be in the forefront of
      health care delivery, they are still widely misperceived, underutilized, and
      unrecognized as mainstream health care providers. In this era of health care
      reform, it is essential that the role and image of the nurse-midwife be clearly
      defined to the general public, maternity care consumer, fellow health care
      providers, and legislators.

PMID- 8299061
TI  - The research journal club: a mechanism for research utilization.
AB  - This article identifies the nursing journal club as an important mechanism for
      the evaluation and utilization of nursing research. It explores the CNS's role in
      introducing critical appraisal skills and concepts of research utilization to
      staff. Benner's developmental model for clinical practitioners is suggested as a
      framework for the appropriate introduction of research. Guidelines for developing
      and managing a journal club are presented, as well as suggestions for research
      critique tools and research utilization models.

PMID- 8299062
TI  - Clinical nurse specialist practice: facilitators and barriers.
AB  - Responding to a survey containing open-ended questions, 288 Master's-prepared
      CNSs across the United States identified role components that are a part of their
      practice, described health care system changes affecting implementation of their
      roles, and described resources that were or would be supportive of successful
      role implementation. Role categories related to patient care/consultation,
      education, research, administration, and professional development were ranked in
      that order according to time spent in each activity. Issues related to
      institutional cost containment and employment of CNSs were described most
      frequently as affecting role implementation. Nursing administrative support was
      indicated as the resource most crucial for role success. Specific suggestions for
      successful implementation of CNS role are described.

PMID- 8299063
TI  - All that power.

PMID- 8299064
TI  - Critical care clinical nurse specialist in home health care: survey results.
AB  - Two surveys were designed and sent to health care providers in the Philadelphia
      metropolitan area. The purpose of the surveys was to explore whether there was a
      need for critical care CNSs (CCCNS) in the field of high-tech, complex home care
      and to determine the characteristics of that role. In addition, the surveys
      sought to identify the necessary curriculum content a CCCNS graduate program
      should include to prepare individuals for practice in home care. One survey was
      sent to home care providers and an amended version to in-hospital personnel
      identified as responsible for discharge planning. Eighty-three percent of the
      home care survey respondents and 85% of the in-hospital survey respondents
      perceived a need for a CCCNS in the high-tech, complex home care field. The
      identified roles of the CCCNS in home care were similar for both respondent
      groups. They included consultant to the home care agency, patient-family
      educator, staff educator, and hospital-to-home coordinator. Some suggestions for
      curriculum content included courses on technology, discharge planning, health
      policy, and chronic illness. Although a preliminary exploration, the surveys
      demonstrated the existence of patients with high-tech, complex home care needs
      and supported the belief that CCCNSs have a role in their care.

PMID- 8299065
TI  - Hospital privileges for clinical nurse specialists.

PMID- 8299066
TI  - Factors influencing the implementation of the CNS role in a private practice.
AB  - Factors to be considered by the CNS before implementing the role in private
      practice with a physician are discussed. Four CNSs were interviewed regarding
      their experiences in such a practice. The CNS subroles of expert practitioner,
      educator, consultant, and researcher are described as they apply in private
      practice with a physician. A four-step process is proposed to guide the CNS
      considering entry into private practice. The steps discussed are: self
      assessment, evaluation of the legal and financial aspects, development of
      marketing and cost-justification strategies, and negotiating for a position. A
      method for cost justification is proposed, and some elements of marketing and
      negotiating are reviewed.

PMID- 8299067
TI  - A combined role of clinical nurse specialist and coordinator: optimizing
      continuity of care in an autologous bone marrow transplant program.
AB  - Bone marrow transplant patients pose challenges to achieving continuity of care,
      as they have complex needs, care is chronic, and patients cross numerous health
      care settings. Traditionally, bone marrow transplant centers have attempted to
      meet patient needs by separating needs into preadmission, inpatient, and
      outpatient and by hiring two to three nurses to work within each of those time
      periods. This paper describes how one CNS working with bone marrow transplant
      patients enlarged the role to incorporate functions typically performed by a
      coordinator position in order to better meet the needs of patients along the
      entire illness continuum. This paper outlines the principles necessary to
      implement the combined position, and the operationalization and analysis of the
      effectiveness of this approach in order to achieve continuity of care.

PMID- 8299068
TI  - The CNS consultant and change.

PMID- 8299070
TI  - The CNS as ambassador.

PMID- 8299069
TI  - Understanding staff nurse responses to change: utilization of a grief-change
      framework to facilitate innovation.
AB  - This paper reviews the literature on the psychological effects of change and
      discusses the impact of an overarching organizational change on the staff nurses
      of a large oncology unit in the Midwest. Their reactions are compared with a
      grief-change framework synthesized from the literature. This framework was useful
      in explaining staff nurse behaviors and attitudes, and offered interventions
      specific to each stage of the change process useful to the CNS. Dissemination of
      this information is discussed, as well as implications for advanced nursing
      practice.

PMID- 8299071
TI  - Commendations: a resource intervention for clinical practice.
AB  - Nurses form collaborative relationships with patients and families to provide
      care and to assist families in dealing with health problems. Commendations is one
      intervention nurses can use to empower patients and families in order to enhance
      the forming and maintenance of a collaborative relationship. Commendations are
      statements of special praise that are specific to some aspect of patient and/or
      family functioning. The focus of this paper is the use of commendations in
      clinical practice. The theoretical orientation that informs the use of
      commendations is family systems nursing, which highlights family resources. A
      practical approach to the content, process, and timing of commendations is
      presented, and the use of commendations in practice is illustrated by example.

PMID- 8299072
TI  - The need to reexamine axillary lymph node dissection in invasive breast cancer.

PMID- 8299073
TI  - Smoking, gender, and age as risk factors for site-specific intraoral squamous
      cell carcinoma. A case-series analysis.
AB  - BACKGROUND: Studies assessing risk factors for oral cancer do not generally
      report results for specific oral sites. The purpose of the current study was to
      examine differences in the distribution of age, gender, and tobacco use by
      intraoral site in a series of oral cancer cases. METHODS: Information on gender,
      age at diagnosis, and lesion location was obtained for all incident cases of oral
      squamous cell carcinoma diagnosed through the University of Connecticut Oral
      Pathology Biopsy Service during the period 1987-1991 (N = 150). Information on
      tobacco use was obtained through a telephone interview or from medical or dental
      records. RESULTS: The tongue, floor of the mouth (FOM), and gingiva,
      respectively, were the most commonly affected sites. The male-to-female ratio was
      greatest for FOM cancer (3.4) and lowest for gingival cancer (0.5). The mean age
      at diagnosis did not differ significantly by site. The percentage of smokers
      among cases of FOM, tongue, and gingival cancer was 97%, 64%, and 50%,
      respectively. When multiple logistic regression was used to compare FOM and
      gingival cancer, gender and smoking remained significant predictors. The odds of
      smoking among patients with FOM cancer were 32 times the odds of smoking among
      patients with gingival cancer (odds ratio for age, gender adjusted = 32.6, 3.3
      323.5). CONCLUSIONS: The findings suggest that cancer of the FOM is more strongly
      associated with smoking than is cancer of the gingiva and, perhaps, the tongue.
      The reported results should be interpreted cautiously in light of study
      limitations, which include the absence of information on alcohol consumption and
      lack of a noncancer control group.

PMID- 8299074
TI  - Expression of laminin, collagen IV, fibronectin, and type IV collagenase in
      gastric carcinoma. An immunohistochemical study of 87 patients.
AB  - BACKGROUND: This study attempted to determine if there is a pattern of
      matrix/matrix-degrading-enzyme immunoreactivity related to the morphologic types
      of gastric carcinoma or to their invasiveness. METHODS: The authors performed an
      immunohistochemical study of the basement membrane antigens laminin and collagen
      IV, fibronectin, and Type IV collagenase in a series of 87 gastric carcinomas and
      their respective nodal metastases (n = 329). RESULTS: Laminin expression was
      observed almost exclusively in carcinomas of the intestinal type. The expression
      of collagen IV was significantly higher in intestinal (52%) and atypical (44%)
      carcinomas than in diffuse (10%) carcinomas; collagen IV expression also was
      significantly correlated with lymphatic invasion and aneuploidy. Ninety percent
      of the carcinomas expressed fibronectin, mostly in the connective tissue at the
      invading edge of the tumors; fibronectin expression was significantly related to
      the expanding growth pattern of the neoplasms. Eighty-six percent of the tumors
      expressed Type IV collagenase, regardless of the histologic type or invasive
      properties. No relationship was observed between the expression of any of the
      antigens and the S-phase fraction of the tumors. No significant differences were
      found between the immunohistochemical profile of the primary tumors and their
      metastases. CONCLUSIONS: The authors conclude that the expression of basement
      membrane antigens is related to the type of gastric carcinomas, rather than the
      cell differentiation or proliferative activity of the tumors. The putative
      prognostic meaning of the relationship between collagen IV immunoreactivity and
      aneuploidy and lymphatic invasiveness of the carcinomas remains to be clarified.

PMID- 8299075
TI  - Primary gastric CD30 (Ki-1)-positive large cell non-Hodgkin's lymphomas. A
      clinicopathologic analysis of six cases.
AB  - BACKGROUND: The CD30/Ki-1 antigen characterizes a series of non-Hodgkin's
      lymphomas (NHL) predominantly showing anaplastic large cell (ALCL) morphology and
      frequently involving the skin and other extranodal sites. In cutaneous large cell
      lymphomas, the CD30 expression was indicated as a favorable prognostic marker
      independently from cytology, anaplastic versus nonanaplastic. The stomach is the
      most common site of extranodal lymphomas in the adult population, but primary
      gastric CD30+ lymphomas have been reported rarely. METHODS: The clinical,
      morphologic, and immunohistochemical features of six cases with primary CD30/Ki
      1+ gastric large cell lymphomas were analyzed. RESULTS: The mean age of patients
      was 64 years with a prevalence of women (M:F ration = 1:2). Patients were
      assigned to Stage IE or IIE. Three of them died of disease, whereas the others
      are still alive (mean follow-up, 18 months). Three of six cases had ALCL
      morphology, whereas other cases had centroblastic, immunoblastic, and high-grade
      mucosa-associated lymphoid tissue lymphoma. Immunohistochemistry revealed a B
      cell phenotype in three of six cases; a T-cell phenotype in one of six cases; and
      a null, non-B, non-T phenotype in two of six cases. CONCLUSIONS: Within CD30+
      primary gastric large cell lymphomas, cytology, anaplastic versus nonanaplastic,
      did not affect clinical presentation and/or prognosis. The survival rate of the
      patients studied is in keeping with literature reports regarding prognosis of
      primary high-grade gastric NHL. The findings suggest that clinical behavior of
      this extranodal lymphoma is more closely related to clinical symptoms and initial
      stage of disease than to CD30 expression.

PMID- 8299076
TI  - Perineural invasion as a predictor of recurrence of gastric cancer.
AB  - BACKGROUND: Perineural invasion (PNI) plays a role in local invasion of
      pancreatic, biliary tract, and large intestine cancers and greatly affects the
      prognosis. Although PNI of gastric cancer has been reported rarely, the authors
      previously reported the usefulness of immunohistochemical staining with laminin
      in evaluating PNI. METHOD: PNI was studied histochemically in 283 patients with
      gastric tumors of T2 or greater depth of invasion resected between 1982 and 1989.
      The relationships between PNI and histopathologic findings, type of recurrence,
      and prognosis also were studied. RESULTS: Of the 216 patients who underwent
      resection for cure, 103 experienced tumor recurrence. Recurrence correlated
      significantly with lymphatic vessel invasion, lymph node metastasis, and PNI.
      Peritoneal recurrence was found in 65 (63.1%) of the 103 patients with tumor
      recurrence and correlated most significantly with PNI in T2 tumors. The 5-year
      survival rate was 71.3% for patients with PNI-negative tumors, significantly
      higher than the 5-year survival rate (23.7%) for patients with PNI-positive
      tumors. A multivariate analysis using a Cox regression model of the relationship
      between histopathologic findings and prognosis demonstrated that the presence of
      PNI had the greatest influence on prognosis. CONCLUSION: The evaluation of PNI is
      useful in determining the prognosis of gastric cancer of T2 class with no serosal
      invasion.

PMID- 8299077
TI  - Quality of life during chemotherapy in patients with symptomatic advanced
      colorectal cancer. The Nordic Gastrointestinal Tumor Adjuvant Therapy Group.
AB  - BACKGROUND: To increase the knowledge about the palliative effects of
      chemotherapy in patients with symptomatic advanced colorectal cancer, physician-
      and patient-rated "quality of life" was studied in a randomized multicenter trial
      comparing a regimen of methotrexate/5-fluorouracil (5-FU) followed by leucovorin
      rescue (MFL) with a regimen of 5-FU/leucovorin (FLV). METHODS: Between January
      1989 and December 1990, 70 patients completed a quality of life questionnaire at
      randomization and after every fourth treatment course. At one of the hospitals,
      the evaluation was done as an interview (interview group, n = 24), whereas a
      questionnaire was used at the other hospitals (questionnaire group, n = 46).
      RESULTS: Objective responses (complete response plus partial response) were
      obtained in 15 (21%) patients, subjective responses in 29 (41%) patients, and an
      overall improved quality of life in 25 (36%) patients. In addition, 16 (23%)
      patients had unchanged quality of life during at least 4 months. There was a
      correlation between objective responses, subjective responses, and improvements
      in quality of life, although discrepancies were noticed, particularly in patients
      with only slight symptoms. Response rates were higher in the interview group than
      in the questionnaire group (P < 0.01). This difference could be related to a more
      favorable outcome when 5-FU was given as a bolus injection, rather than as a
      short-term infusion (more than 5 minutes). CONCLUSIONS: Improvements or prolonged
      stabilization of disease in quality of life can be achieved in at least half of
      the patients with tumor-related symptoms. However, factors related to the
      administration of chemotherapy may influence this proportion.

PMID- 8299078
TI  - Plasma prolactin in patients with colorectal cancer. Value in follow-up and as a
      prognosticator.
AB  - BACKGROUND: Preoperative plasma prolactin and carcinoembryonic antigen (CEA)
      levels were assessed to monitor disease recurrence and to identify low-risk and
      high-risk patients with Dukes B or C colorectal cancer. METHODS: Prolactin and
      CEA were estimated by radioimmunoassay method. Blood samples were collected
      preoperatively and sequentially thereafter from patients with colorectal cancer
      (N = 114); the samples were compared with samples from age-matched healthy
      control subjects (smokers and nonsmokers, N = 45). For rest of the analysis,
      patients with Dukes A disease (N = 7) were not included because of the small
      number. In monitoring recurrences, the criteria for positive test for the two
      markers was a continual increase in the marker level after an initial decrease or
      persistent high level of the marker. These were the indicators of relapse or no
      response to treatment. To determine the efficacy of the preoperative markers, the
      patients were grouped according to disease status at the end of 3 years, i.e.,
      patients who had response to the treatment modalities (N = 52) and patients who
      later had progressive disease (N = 55). To determine the prognostic significance
      of preoperative marker levels, the patients were divided according to the cutoff
      levels (upper normal limits); for prolactin the cutoff level was 20.0 ng/ml
      plasma, and for CEA it was 5.0 ng/ml plasma. RESULTS: Both of the markers were
      significantly high in patients with colorectal cancer compared with the markers
      of their respective control subjects (P < 0.0001). In monitoring disease course,
      the predictive power of prolactin was 100%, whereas that of CEA was 66%.
      Prolactin showed a lead time of 2-3 months. Preoperative prolactin levels were
      significantly higher in patients who later had progressive disease (P < 0.001)
      than in patients who had response to the treatments. However, such an intergroup
      variation was not observed for CEA. Patients with preoperative levels of
      prolactin greater than 20.0 ng/ml had shorter overall survival times than did
      those with prolactin levels less than 20.0 ng/ml plasma; such a trend was not
      observed for patients with CEA levels less than 5.0 ng/ml and those with CEA
      levels greater than 5.0 ng/ml plasma. CONCLUSION: Prolactin is a better overall
      marker than is CEA in patients with Dukes B or C colorectal cancer. The authors
      recommend the use of plasma prolactin levels to help identify low-risk and high
      risk patient subgroups so that high-risk patients may be followed up more
      intensely and treated accordingly. Hyperprolactinemic patients with Dukes B or C
      disease have shortened survival time.

PMID- 8299079
TI  - Localization of tumor-reactive lymph node lymphocytes in vivo using radiolabeled
      monoclonal antibody.
AB  - BACKGROUND: Lymph node lymphocytes vary in their responsiveness to tumor. A
      technique has been developed that uses radiolabeled monoclonal antibody (MoAb)
      against the tumor-associated mucin, TAG-72, and a gamma-detecting probe by which
      lymph nodes containing microscopic tumor and/or shed TAG-72 can be identified in
      vivo. The immunologic characteristics of these lymph nodes were examined.
      METHODS: Patients with colon cancer received 125I-labeled MoAb CC49 by
      intravenous injection preoperatively. During laparotomy lymph nodes that appeared
      normal on inspection and palpation but which contained radiolabeled MoAb were
      identified using a hand-held gamma-detecting probe. These lymph nodes and other
      lymph node and tumor specimens were resected for analysis. RESULTS: Lymph nodes
      identified by the probe were found by immunohistochemical studies to contain
      microscopic tumor and/or shed antigen associated with germinal centers. They were
      characterized by greater CD4+:CD8+ ratios, rates of expansion, and cytolytic
      activity compared with lymphocytes from lymph nodes with macroscopic tumor,
      noninvolved lymph nodes, and tumors. All lymph node lymphocytes identified by the
      probe demonstrated significant proliferative responses to autologous tumor and,
      in contrast to lymphocytes from noninvolved lymph nodes, significant
      proliferative responses to allogeneic TAG-72+ tumor cells and to soluble TAG-72+
      mucin. CONCLUSIONS: By locating lymph nodes with microscopic tumor and/or shed
      antigen, the use of radiolabeled MoAb in vivo can be used to reproducibly
      identify tumor-reactive lymph node lymphocytes. This technique may be useful in
      identifying cells for use in adoptive immunotherapy programs and in studying the
      regulation of immune responses in vivo.

PMID- 8299080
TI  - Energy expenditure in patients with hepatocellular carcinoma.
AB  - BACKGROUND: An increase in resting energy expenditure (REE) is considered to
      contribute to the weight loss experienced by patients with cancer. However,
      alternations in basal metabolism vary among patients with different neoplasms.
      REE in patients with hepatocellular carcinoma (HCC), a common malignant tumor in
      Taiwan, was evaluated. METHODS: Fifty-seven male patients with HCC and 60 male
      control subjects without known cancer were entered in the study. The groups did
      not differ significantly in age, body weight, and height. Indirect calorimetry
      was used to measure REE. Oxidative rates of endogenous substrates also were
      calculated. RESULTS: REE was significantly higher in the HCC group than the
      control group (22.12 +/- 0.36 kcal/kg/day versus 20.99 +/- 0.27 kcal/kg/day, P <
      0.05; and 115.3 +/- 4.3 kcal/100 mg creatinine versus 102.2 +/- 3.8 kcal/100 mg
      creatinine, P < 0.05). A higher measured-to-predicted-REE ratio also was observed
      in the HCC group (101.5% +/- 1.4% versus 93.6% +/- 1.0%; P < 0.005). REE in
      patients with HCC did not differ according to whether patients had liver
      cirrhosis or ascites. In addition, REE of patients with large and medium tumors
      were higher than were those of patients with small tumors, but no difference was
      found between the REE of patients with small tumors and the control subjects.
      Also observed were an increase in oxidation of fat with a decrease in oxidation
      of protein in patients with HCC and a relative decrease in the contribution of
      fat with an increase in the contribution of carbohydrates to REE after the
      increase of tumor size. CONCLUSIONS: The results suggest that patients with HCC
      are hypermetabolic and the elevation in REE is related to tumor size, not to the
      presence of liver cirrhosis or ascites.

PMID- 8299081
TI  - Influence of vitamins A, C, and E and beta-carotene on aflatoxin B1 binding to
      DNA in woodchuck hepatocytes.
AB  - BACKGROUND: There is extensive epidemiologic evidence suggesting a protective
      role for micronutrients in cancer incidence. This evidence comes from studies of
      fruit and vegetable intake and serum levels of specific micronutrients. There
      also is limited in vitro evidence demonstrating that micronutrients can influence
      the first step in carcinogenesis, binding of chemical carcinogens to DNA. These
      in vitro studies allow the determination of specific effects of individual
      micronutrients. The influence of micronutrients on DNA binding of aflatoxin B1
      (AFB1), a potent hepatocarcinogen, in mammalian cells is unknown. Woodchuck
      hepatocytes were used as a model to investigate the effects of vitamin A (all
      trans retinol), C (ascorbic acid), ascorbyl palmitate (a synthetic lipophilic
      derivative of ascorbic acid), vitamin E (alpha-tocopherol), and beta-carotene on
      AFB1-DNA binding. METHODS: Woodchuck hepatocytes were treated with 4 doses
      (0.080, 0.40, 2.0, and 10 microM) of [3H]AFB1 or with different combinations of
      AFB1 and the vitamins for 6 hours, and adduct levels determined. Western blot
      analysis of protein extracts of treated cells was used to determine the effects
      of vitamin A and beta-carotene on glutathione-S- transferase M1 levels. RESULTS:
      Vitamin A inhibited formation of AFB1-DNA adducts in a dose-dependent manner
      throughout a concentration range of 34-122 microM by 40-80%. Vitamin C (0.080-10
      mM) was much less effective than vitamin A as an inhibitor of AFB1-DNA binding.
      Treatment with 6.0-48.3 microM ascorbyl palmitate reduced adduct levels at lower
      AFB1 concentrations but had no significant effect at higher AFB1 concentrations.
      beta-Carotene and vitamin E enhanced covalent binding of AFB1 to DNA. Enhancement
      with beta-carotene was observed when both tetrahydrofuran or liposomes were used
      as the administration vehicle. Western blot analysis indicated that neither the
      vitamin A nor beta-carotene treatment affected glutathione-S-transferase M1
      protein levels. CONCLUSIONS: These results demonstrate that micronutrients play a
      complex role in the process of chemical carcinogenesis. Although protective
      effects were seen with several antioxidant vitamins, increased DNA adduct
      formation was observed with beta-carotene and vitamin E. This antioxidant
      activity may be unrelated to the inhibition of DNA adduct formation. Additional
      studies are needed to understand the mechanism of enhanced adduct formation.

PMID- 8299082
TI  - Serum tumor markers in non-small cell lung cancer. A comparative analysis.
AB  - BACKGROUND: The role of serum tumor markers in non-small cell lung cancer (NSCLC)
      remains undefined. New proposed markers have seldom been rigorously compared with
      existing standards. The authors prospectively compared the performance of three
      new monoclonal antibodies (MoAb) (5E8, 5C7, and 1F10) with the established serum
      markers carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC).
      METHODS: The cohort consisted of 45 consecutive out-patients with newly diagnosed
      NSCLC: Control subjects were 38 outpatients with non-neoplastic chronic pulmonary
      diseases. Blood from each patient and control subject was assayed for all five
      tumor markers. An enzyme-linked immunosorbent assay (ELISA) was used to determine
      5E8, 5C7, and 1F10 reactivity. Commercially available kits were used to measure
      SCC by radioimmunoassay and CEA by ELISA: Individual and combinations of tumor
      markers were compared in terms of sensitivity, specificity, and accuracy for
      NSCLC diagnosis. RESULTS: 5E8 plus 5C7 plus 1F10 significantly surpassed SCC plus
      CEA in terms of sensitivity (P < 0.05) and proved the most accurate marker
      combination. Among single markers, 5E8 was most specific, 5C7 most sensitive, and
      5C7 and 1F10 each most accurate, but differences from CEA alone were not
      significant. Subgroup analysis by histologic type and stage demonstrated similar
      findings, and marker combinations yielded little additional diagnostic benefit.
      CONCLUSIONS: 5E8, 5C7, and 1F10 performed marginally better than did CEA and SCC
      in patients with newly diagnosed NSCLC: Many limitations apply in defining a
      clinical niche for these tumor markers in NSCLC, although 5E8, 5C7, and 1F10
      previously have demonstrated a modest prognostic value. An adjunctive role in a
      few specific clinical contexts remains possible.

PMID- 8299083
TI  - Plasma cell dyscrasia with marrow fibrosis. A reversible syndrome mimicking
      agnogenic myeloid metaplasia.
AB  - BACKGROUND: The interrelation between plasma cell dyscrasia and myelofibrosis or
      agnogenic myeloid metaplasia (AMM) is unclear. The existence of two distinct
      syndromes has been proposed: (1) plasma cell dyscrasia associated with simple
      marrow fibrosis caused by the secretion of lymphokines and (2) myeloma coexisting
      with AMM representing two distinct clonal diseases. METHODS: The authors report
      the case of a 68 year-old man seen initially with severe anemia, massive
      splenomegaly, a leuko-erythroblastic blood morphology, and myelofibrosis
      coexisting with massive bone marrow infiltration with IgA lambda-producing
      plasmacytoid cells. RESULTS: Cyclic therapy with vincristine, carmustine,
      cyclophosphamide, melphalan, and prednisone resulted in clinical remission of the
      myeloma lasting for 2 years and complete resolution of all the clinical features
      resembling AMM. CONCLUSIONS: The authors' observations and the report of two
      other patients in whom remission of AMM has been observed after myeloma treatment
      underline the broad spectrum of secondary abnormalities ranging from moderate
      bone marrow fibrosis to the full clinical expression of a syndrome closely
      mimicking AMM. These secondary abnormalities are potentially reversible even in
      the presence of advanced bone marrow fibrosis and massive splenomegaly.

PMID- 8299084
TI  - Evaluation of melanin-related metabolites as markers of melanoma progression.
AB  - BACKGROUND: Urinary excretion of 5-S-cysteinyldopa (5-S-CD) has been used as a
      biochemical marker of melanoma progression. Melanomas produce not only 5-S-CD but
      also 5,6-dihydroxyindole-2-carboxylic acid (5,6DHI2C) as major intermediates in
      melanin formation. 5,6DHI2C is then metabolized to the two O-methyl derivatives,
      5H6MI2C and 6H5MI2C. The aim of this study was to determine which marker in serum
      and urine most sensitively reflected the progression of melanoma. METHODS: Serum
      and 24-hour urine samples were collected and assayed serially by high-performance
      liquid chromatography every 1 to 4 months in 28 patients with primary or
      recurrent melanomas, for up to 48 months. RESULTS: Serum concentration and
      urinary excretion of 5-S-CD and 6H5MI2C in patients with melanoma without
      metastases were close to those obtained from normal subjects. Metastases
      developed in 9 of the 28 patients. In seven of these nine patients, serum or
      urinary 5-S-CD values were elevated before or at the time of clinical detection
      of visceral metastases. However, serum 5-S-CD was elevated significantly earlier
      and reflected melanoma progression better than the physical examination and/or
      laboratory tests, such as scintigraphy and echography. Serum 6H5MI2C values
      exceeded the normal range shortly before death in three patients, and urinary
      6H5MI2C did not increase at any stage in most patients, therefore these
      metabolites did not reflect progression of disease. CONCLUSIONS: Among the four
      markers, serum 5-S-CD appears to be the best biochemical marker for the detection
      of progression of melanotic melanoma, a value of more than 10 nmol/l suggesting
      the presence of metastasis.

PMID- 8299085
TI  - Resectable retroperitoneal soft tissue sarcomas. The effect of extent of
      resection and postoperative radiation therapy on local tumor control.
AB  - BACKGROUND: Soft tissue malignancies of the retroperitoneum are rare. Surgery is
      commonly considered the first choice of treatment. There is still no consensus
      concerning the precise value of the extent of surgery and the value of additional
      treatment modalities. METHODS: From 1973 to 1990, 34 patients were initially
      treated by surgery for retroperitoneal soft tissue sarcomas at the Netherlands
      Cancer Institute. In a retrospective study, the prognostic effect of extent of
      primary surgery and postoperative radiation therapy was examined. RESULTS:
      Liposarcomas (47%) and leiomyosarcomas (29%) were the histologic types most
      commonly found. Grade of malignancy was defined as medium to high (II/III) in 44%
      and as low (I) in 38%. Complete (extended or marginal) resection of the tumor was
      achieved in 29 patients. After complete resection, the 5-year survival rate and
      the local recurrence rate were 35% and 63%, respectively. Extended surgery
      (performed in eight patients) showed a local recurrence rate of 50%. Thirteen
      patients received high-dose postoperative radiation therapy, which was found to
      have a significant favorable effect on the recurrence-free interval (P < 0.01).
      CONCLUSIONS: We conclude that complete (extended) resection followed by high-dose
      postoperative radiation therapy improves the prognostic outcome of patients with
      retroperitoneal soft tissue sarcomas.

PMID- 8299086
TI  - Autosomal dominant inheritance of early-onset breast cancer. Implications for
      risk prediction.
AB  - BACKGROUND: Improvements in screening techniques have made significant
      contributions to the early detection of breast cancer. Physicians thus face the
      task of providing appropriate screening schedules for their patients. One group
      for whom this is particularly important are those women with a family history of
      breast cancer. METHODS: In this report, data from the Cancer and Steroid Hormone
      Study, a population-based, case-control study conducted by the Centers for
      Disease Control, are used to provide age-specific risk estimates of breast cancer
      for women with a family history of breast cancer. The data set includes 4730
      patients with histologically confirmed breast cancer age 20-54 years and 4688
      control subjects who were frequency matched to patients by geographic region and
      5-year age intervals. The data set also includes family histories of breast
      cancer in mothers and sisters of both patients and control subjects. RESULTS:
      Genetic models fit previously to these data by the authors have provided evidence
      for a rare autosomal dominant allele that results in increased susceptibility to
      breast cancer. In addition, these models predict that women who carry the allele
      are at greater risk of developing breast cancer at any age than are women who do
      not carry the allele. The increase in risk in carriers versus noncarriers does,
      however, decrease with increasing age. Based on the parameters of this model, age
      specific risks for a woman with one or more relatives affected with breast cancer
      at various ages at onset are given. CONCLUSIONS: These tables can be used for the
      purpose of counseling women at high risk of breast cancer development, that is,
      women with a family history of breast cancer.

PMID- 8299087
TI  - Effect of tamoxifen on plasma lipids and lipoproteins in postmenopausal women
      with breast cancer.
AB  - BACKGROUND: Adjuvant tamoxifen therapy is given to large and increasing numbers
      of women with early-stage breast cancer. The effects of this drug on plasma
      lipids and lipoprotein profiles are important, because cardiovascular disease
      also develops over time in a large percentage of tamoxifen-treated postmenopausal
      women. The purpose of the study was to evaluate the effects of tamoxifen on
      plasma lipid and lipoprotein profiles in postmenopausal Indian women who were
      disease-free after primary treatment for breast cancer. METHODS: A short-term
      evaluation of 6 months of tamoxifen therapy (10 mg twice a day) in 45
      postmenopausal women was conducted. The plasma lipids and lipoprotein levels were
      evaluated before and after 3 and 6 months of tamoxifen treatment. RESULTS: At 3
      and 6 months' evaluation, patients receiving tamoxifen showed significantly
      decreased levels of total cholesterol, free cholesterol, and low-density
      lipoprotein cholesterol (P < 0.001 for each) and increased levels of plasma
      triglycerides, free fatty acids, very low density lipoprotein cholesterol, and
      high-density lipoprotein cholesterol. CONCLUSION: The results suggest that
      tamoxifen therapy benefits postmenopausal patients with breast cancer, with
      likely reduction in the risk of cardiovascular disease.

PMID- 8299088
TI  - Axillary lymph node dissection for T1a breast carcinoma. Is it indicated?
AB  - BACKGROUND: Axillary dissection has been a routine part of breast cancer
      treatment for more than 100 years. Axillary node involvement is the single most
      important prognostic variable in patients with breast cancer. Recently, routine
      node dissection has been eliminated for intraductal carcinoma because so few
      patients had positive nodes. With the availability of numerous histologic
      prognosticators and the development of new immunochemical prognostic indicators,
      it is time to consider eliminating routine node dissection for lesions more
      advanced than duct carcinoma in situ (DCIS) but with extremely low likelihood of
      axillary involvement. METHODS: Axillary node positivity, disease-free survival,
      and breast cancer-specific survival were determined for six breast cancer
      subgroups by T category: Tis (DCIS), T1a, T1b, T1c, T2, and T3. RESULTS: Nodal
      positivity for DCIS was 0%; for T1a lesions, 3%. A large increase in nodal
      positivity was seen in lesions larger than 5 mm. (T1b, 17%; T1c, 32%; T2, 44%;
      T3, 60%). The rate of nodal positivity was statistically different as each T
      category was compared with the next more advanced T category. The disease-free
      survival and breast cancer-specific survival decreased with every increment in T
      value. CONCLUSIONS: Axillary node positivity increases as the size of the
      invasive component increases and is an excellent predictor of DSF and breast
      cancer-specific survival. Consideration should be given to eliminating axillary
      node dissection for T1a lesions because of the low yield of positive nodes.
      Axillary node dissection should be performed routinely for T1b lesions and
      larger.

PMID- 8299089
TI  - Small cell carcinoma of the cervix. A clinicopathologic study of 26 patients.
AB  - BACKGROUND: Small cell carcinoma of the cervix is a rare and aggressive tumor.
      Most gynecologic oncology centers have little experience with this tumor, and
      only small series have been published. METHODS: Twenty-six patients with small
      cell carcinoma of the uterine cervix were treated at the Norwegian Radium
      Hospital. Clinical data, immunohistochemical characteristics, and infection with
      human papillomavirus were studied. RESULTS: Twelve tumors were of oat cell type
      and 14 of intermediate cell type. Twelve tumors were associated with other forms
      of carcinoma: squamous cell carcinoma (6 tumors), adenocarcinoma (5 tumors), and
      adenocarcinoma in situ (1 tumor). Neuroendocrine differentiation was expressed in
      79% of the tumors. Human papillomavirus (HPV)-18 was detected in 40% of the
      tumors and HPV-16 in 28%. Fifteen patients had Stage I disease, 7 had Stage II, 2
      had Stage III, and 3 had Stage IV. Fourteen patients with Stage I and II disease
      underwent radical hysterectomy with pelvic lymph node dissection. In four, the
      operation was preceded by intracavitary radiation treatment. The patients with
      Stage II, III, and IV disease were treated with a combination of intracavitary
      radium, external beam radiation therapy, and chemotherapy. The 5-year survival
      rate was 14%. Four patients are alive, one with recurrent disease 50 months after
      diagnosis. Three patients free of disease have been followed up 26, 54, and 101
      months, respectively. CONCLUSIONS: Small cell carcinoma of the cervix is an
      aggressive tumor with a propensity for rapid recurrence; it is associated with
      high mortality.

PMID- 8299090
TI  - An Eastern Cooperative Oncology Group phase II trial of trimetrexate in the
      treatment of advanced urothelial carcinoma.
AB  - BACKGROUND: Trimetrexate is an antifol that differs from methotrexate in ways
      that may be clinically important. Because methotrexate has activity in advanced
      bladder cancer, this trial was initiated. METHODS: Ambulatory patients with
      advanced urothelial carcinoma were treated with the nonclassic antifol
      trimetrexate at the intravenous dose of 8 mg/m2 daily for 5 consecutive days
      every 3 weeks (4 mg/m2 daily for 5 consecutive days for patients with creatinine
      levels greater than 1.6 mg/dl). RESULTS: Of the 48 patients in the study, one had
      a complete response and seven had partial responses, for an overall response rate
      of 17% (exact 95% confidence interval, 7-30%). The response rate in patients who
      had received prior methotrexate was 18%, suggesting lack of complete cross
      resistance. Toxicity was manageable and primarily mucosal, gastrointestinal, and
      myelosuppressive. CONCLUSIONS: Trimetrexate has as much activity as other single
      agents in advanced urothelial carcinoma. Combination therapy, possibly with
      cisplatin, platinum analogs, or other antifols, using trimetrexate should be
      studied.

PMID- 8299091
TI  - Optic nerve invasion of retinoblastoma. Metastatic potential and clinical risk
      factors.
AB  - BACKGROUND: Optic nerve invasion is one of the predictors for retinoblastoma
      metastases. This study was designed to investigate the risk of optic nerve
      invasion and clinical features that may identify those children with optic nerve
      invasion. METHODS: We reviewed the charts of 289 children with retinoblastoma
      treated initially with enucleation. Logistic regression analysis was performed to
      assess the risk for metastases from varying degrees of optic nerve invasion and
      to assess the clinical and histopathologic predictors of optic nerve invasion.
      RESULTS: There were 84 eyes (29%) with optic nerve invasion. The invasion was
      prelamina cribrosa in 44 cases (15%), up to but not posterior to the lamina
      cribrosa in 21 cases (7%), posterior to the lamina cribrosa but not to the cut
      end of the optic nerve in 17 cases (6%), and to the site of optic nerve
      transection in 2 cases (1%). Patients with optic nerve invasion were more likely
      to develop metastasis (P = 0.0016), particularly those with invasion to the
      postlaminar and cut section of the optic nerve (P = 0.0001). Development of
      metastasis was not statistically associated with laminar or prelaminar
      involvement. If those patients with choroidal invasion simultaneous with optic
      nerve invasion were excluded from evaluation, the presence of optic nerve
      invasion alone was not significant for development of metastasis. The clinical
      factors found to be predictive for optic nerve invasion from a univariate
      analysis included exophytic growth pattern (P = 0.011), elevated intraocular
      pressure (> 22 mm Hg) (P = 0.02), and tumor thickness greater than or equal to 15
      mm (P = 0.03). The histopathologic factor significantly associated with optic
      nerve invasion (univariate analysis) was simultaneous choroidal invasion (P =
      0.001). A trend toward an association with optic nerve invasion was found with
      vitreous hemorrhage (P = 0.06), iris neovascularization (P = 0.10), and poorly
      differentiated retinoblastoma (P = 0.07). A multivariate analysis showed the most
      significant clinical factors to be exophytic growth pattern (P = 0.002), tumor
      thickness greater than or equal to 15 mm (P = 0.01), and vitreous hemorrhage (P =
      0.05). CONCLUSIONS: Optic nerve invasion of retinoblastoma beyond the lamina
      cribrosa is associated with a greater metastatic risk. Large exophytic
      retinoblastoma with secondary glaucoma is at highest risk for optic nerve
      invasion.

PMID- 8299092
TI  - A randomized study with the pineal hormone melatonin versus supportive care alone
      in patients with brain metastases due to solid neoplasms.
AB  - BACKGROUND: Unresectable brain metastases remain an untreatable disease. Because
      of its antitumor cytostatic action and its anticonvulsant effect, the pineal
      hormone melatonin could constitute a new effective agent in the treatment of
      brain metastases. The current study was performed to evaluate the effect of
      melatonin on the survival time in patients with brain metastases due to solid
      neoplasms. METHODS: The study included 50 patients, who were randomized to be
      treated with supportive care alone (steroids plus anticonvulsant agents) or with
      supportive care plus melatonin (20 mg/day at 8:00 p.m. orally). RESULTS: The
      survival at 1 year, free-from-brain-progression period, and mean survival time
      were significantly higher in patients treated with melatonin than in those who
      received the supportive care alone. Conversely, steroid-induced metabolic and
      infective complications were significantly more frequent in patients treated with
      supportive care alone than in those concomitantly treated with melatonin.
      CONCLUSIONS: The pineal hormone melatonin may be able to improve the survival
      time and the quality of life in patients with brain metastases due to solid
      tumors.

PMID- 8299093
TI  - Paraneoplastic cholestasis and hypercoagulability associated with medullary
      thyroid carcinoma. Resolution with tumor debulking.
AB  - The authors report a 69-year-old woman with a hypercoagulable state manifesting
      as superior sagittal sinus thrombosis, thrombocytosis, right lower extremity deep
      venous thrombosis, and subsequent pulmonary embolus. The liver enzyme values were
      elevated in a cholestatic pattern. Carcinoembryonic antigen level was markedly
      elevated. Evaluation revealed that her longstanding "goiter" had slowly enlarged
      during the past 6 years. The serum calcitonin level was markedly elevated.
      Subsequent biopsy revealed medullary thyroid carcinoma. Surgical debulking of the
      tumor and lymph nodes resulted in substantial reduction of the calcitonin and
      carcinoembryonic antigen levels in a matter of days. Long-term follow-up revealed
      normalization of cholestasis and resolution of the hypercoagulable state. Review
      of the literature revealed no previously reported cholestasis or hypercoagulable
      state associated with medullary thyroid carcinoma. The literature on
      paraneoplastic cholestasis, carcinoembryonic antigen production, and
      hypercoagulable states is reviewed.

PMID- 8299094
TI  - Non-Hodgkin's lymphoma in Saskatchewan. A review of 10 years' experience.
AB  - BACKGROUND: The incidence and treatment of non-Hodgkin's lymphoma (NHL) have
      changed in recent years. This study was intended to compare current features with
      a previous study (1966-1975) and assess the impact of these changes in our
      jurisdiction. METHODS: Clinical features and treatment of 547 patients with NHL
      registered at our center from January 1980 through December 1989 were reviewed,
      including reassessment of histologic type in each patient. Multivariate analysis
      of potential pretreatment prognostic factors was performed using the Cox
      proportional hazards model, and survival was analyzed in relation to treatment
      outcome. RESULTS: This review includes virtually all incident cases of NHL in a
      defined geographic area, representing an average annual incidence of 11.3/100,000
      population. The male-to-female ratio was 1.1:1, median age was 65 years (range, 4
      92 years). Median survival time (MST) of 482 patients with disease diagnosed
      antemortem was 4.8 years (95% confidence interval [CI], 3.7-6.1 years), 52% of
      whom have died. Thirty-nine percent of patients with disease classified by the
      International Working Formulation (IWF) had low-grade disease (MST, 103 months);
      27% had intermediate disease (MST, 62 months), and 30% had high-grade disease
      (MST, 35 months). Sixteen percent of patients had associated neoplasms: 4 acute
      leukemias, 35 skin cancers, and 37 miscellaneous solid tumors. Results of
      radiation therapy (RT), chemotherapy (CT), and combined CT/RT were analyzed.
      Survival correlated strongly with responsiveness to treatment. Considering all
      patients treated with CT, anthracycline-containing CT was associated with the
      highest response rate, and survival time (more than 48 months) may have been
      affected by the addition of this agent. A survival advantage for patients with
      bulky Stage I and II disease treated with consolidative RT after CT is suggested,
      but not for more advanced stage disease. The proportional hazards model
      identified histologic type, disease stage, patient age, hemoglobin level, lactate
      dehydrogenase (LDH) level, bulky abdominal disease, and systemic "B" symptoms as
      significant independent prognostic factors influencing survival. CONCLUSIONS: The
      incidence of NHL has increased, and the survival of patients with high-grade
      disease has improved significantly since the previous study. A high incidence of
      other associated malignancies was demonstrated in this group of patients with
      NHL. Recognition of prognostic factors should permit a rational application of
      innovative treatments for patients in unfavorable prognostic categories.

PMID- 8299095
TI  - The addition of ondansetron to the combination of metoclopramide, dexamethasone,
      and lorazepam did not improve vomiting prevention in patients receiving high-dose
      cisplatin.
AB  - BACKGROUND: Serotonin has been shown to be an important mediator of chemotherapy
      induced vomiting. Ondansetron is a potent and highly specific antagonist of the 5
      HT3 serotonin receptor. The objective of the current trial was to determine if
      the addition of ondansetron to the combination of metoclopramide, dexamethasone,
      and lorazepam (MDL) could improve the control of vomiting in patients receiving
      high-dose cisplatin. The three-drug MDL antiemetic regimen has been shown to
      prevent vomiting in 67% of patients receiving high-dose cisplatin. METHODS:
      Thirty-two patients receiving initial cisplatin (greater than or equal to 100
      mg/m2) were given intravenous lorazepam, 1.5 mg/m2 (maximum dose, 3 mg), one dose
      45 minutes before cisplatin; metoclopramide, 3 mg/kg 40 minutes before and 90
      minutes after cisplatin; ondansetron, 0.3 mg/kg 25 minutes before and 3.5 hours
      after cisplatin; and dexamethasone, 20 mg, one dose 10 minutes before cisplatin.
      Patients were followed for 24 hours after cisplatin administration. RESULTS:
      Vomiting was prevented in 67% of patients (95% confidence interval, 47-83%).
      Adverse effects were mild and transient and included sedation, headache, serum
      aspartate transaminase, and alanine transaminase elevations, akathisia, and
      hiccups. CONCLUSIONS: Vomiting was prevented in two thirds of patients treated
      with MDL plus ondansetron, a result similar to that observed in earlier trials of
      MDL alone. The lack of improvement in emetic control by the addition of
      ondansetron suggests that vomiting mediated through 5-HT3 receptors is already
      effectively blocked. Emesis that occurs despite pretreatment with MDL is likely
      mediated by other mechanisms.

PMID- 8299096
TI  - Minnesota population cancer risk.
AB  - BACKGROUND: The Minnesota Cancer Surveillance System (MCSS) provides information
      on the occurrence of newly diagnosed cancers among Minnesota residents. Cancer is
      a major cause of death and morbidity in older persons. Population cancer risk
      (PCR) was assessed as a measure of the number of cancers that will occur in the
      lifetime of 1000 persons. METHODS: Approximately 98.6% of all cancers diagnosed
      in residents of Minnesota are reported by pathologists to the MCSS. By
      statistical methodology an estimate was made of the total number of cancers that
      will occur in the lifetime of 1000 people (PCR). The calculation assumes people
      born today will have the 1988-1990 Minnesota cancer incidence and life expectancy
      rates. RESULTS: Incidence rates for all cancers in Minnesota have been
      increasing. Life expectancy in Minnesota is greater than in most areas of the
      United States. Approximately 50% of all cancers occurred in Minnesotans older
      than 70 years. The overall PCR is 459 cancers per 1000 lifetimes. It is estimated
      that by the year 2020 more than 100,000 living Minnesotans will have had cancer
      diagnosed during their lifetime. CONCLUSION: During the next 20 years, as the
      Baby Boomer generation in Minnesota moves into the high-risk years for cancer,
      the number of newly diagnosed cancers will increase disproportionately more than
      the increase in size of the older population. In view of the projected number of
      patients with cancer by the year 2020, cancer care will be different from what it
      is today. Geriatric cancer care will become a significant medical, public health,
      economic, bioethical, and social issue.

PMID- 8299097
TI  - Overcoming tumor necrosis factor-alpha resistance of human renal and ovarian
      carcinoma cells by combination treatment with buthionine sulfoximine and tumor
      necrosis factor-alpha. Role of tumor necrosis factor-alpha mRNA down-regulation
      in tumor cell sensitization.
AB  - BACKGROUND: Previous studies have reported the glutathione plays a central role
      in a wide range of cellular functions, including protection, detoxification,
      transport, and metabolism. Buthionine sulfoximine (BSO), a specific inhibitor of
      gamma-glutamyl-cysteine synthetase, depletes intracellular glutathione. The study
      investigates the cytotoxic effect of BSO and tumor necrosis factor-alpha (TNF
      alpha) used in combination on TNF-alpha-resistant human renal and ovarian cancer
      cells. METHODS: Cytotoxicity was determined by a 1-day microculture tetrazolium
      dye assay. TNF-alpha mRNA was examined by Northern blot analysis. RESULTS:
      Combination treatment of TNF-alpha-resistant R4 and R11 human renal cell
      carcinoma cells with BSO and TNF-alpha overcame their resistance to TNF-alpha. In
      addition, the combination of BSO and TNF-alpha resulted in a synergistic
      cytotoxic effect on TNF-alpha-resistant OVC-8 and C30 human ovarian cancer cells.
      Treatment of R4, R11, and OVC-8 cells with TNF-alpha in combination with
      glutathione or N-acetyl-cysteine (NAC) showed an antagonistic cytotoxic effect. A
      possible mechanism of resistance to TNF-alpha in tumor cells is the expression of
      TNF-alpha mRNA or protein. R4 cells and OVC-8 cells constitutively expressed mRNA
      for TNF-alpha. Treatment of R4 cells or OVC-8 cells with BSO down-regulated the
      expression of TNF-alpha mRNA; however, treatment with TNF-alpha up-regulated the
      expression of TNF-alpha mRNA. When BSO was used in combination with TNF-alpha,
      the level of TNF-alpha mRNA enhanced by TNF-alpha was markedly reduced.
      Incubation of R4 cells with glutathione or NAC also down-regulated the expression
      of TNF-alpha mRNA. R11 and C30 cells did not constitutively express mRNA for TNF
      alpha, and the BSO treatment had no effect on the TNF-alpha mRNA level.
      CONCLUSIONS: This study demonstrates that the combination of BSO and TNF-alpha
      can overcome the TNF-alpha resistance of tumor cells and that depletion of
      intracellular glutathione and down-regulation of TNF-alpha mRNA by BSO may play a
      role in the enhanced cytotoxicity seen with the combination of BSO and TNF-alpha.
      There may not be always a correlation between the expression of TNF-alpha mRNA in
      tumor cells and their resistance to TNF-alpha. The synergistic effect obtained
      with established renal cell carcinoma cells and ovarian cancer cells suggests
      that combination treatment with TNF-alpha and BSO could have clinical application
      in the therapy of TNF-alpha-resistant tumors.

PMID- 8299098
TI  - Pyothorax-associated pleural lymphoma. A case evolving from T-cell-rich lymphoid
      infiltration to overt B-cell lymphoma in association with Epstein-Barr virus.
AB  - BACKGROUND: Pyothorax-associated pleural lymphomas (PAPL) occur in patients with
      long-standing pyothorax. Epstein-Barr virus (EBV) plays an important role in its
      development. METHODS: An atypical case of PAPL is reported and its clinical
      features are compared with those of five cases of ordinary PAPL. RESULTS: The
      histology of the lymphoma changed from prominent T-cell infiltration to an overt
      B-cell lymphoma of diffuse, large cell-type. DNA studies of the lymphoma at the
      first presentation demonstrated dual rearrangement in the T-cell receptor beta
      (TCR beta) and immunoglobulin heavy chain J region (IgJH) genes. EBV genome
      analysis demonstrated monoclonal expansion of EBV-infected cells. EBV gene
      products were present only in large lymphocytes with B-cell phenotype. The same
      rearranged band of the IgJH gene, but not clonal rearrangement of the TCR beta
      gene, was observed in the overt B-cell lymphoma at the relapse. The same EBV
      infected clone was observed throughout the course of the disease. The tumor was
      localized at the pyothorax wall, and cell-mediated immunity, reflected by a
      positive tuberculin reaction, was preserved only in the current case.
      CONCLUSIONS: T-cell-rich lymphoid infiltration in the current case is a variant
      of EBV-associated PAPL, which is infiltrated by reactive T-cells with clonal
      accentuation. This is the first documented case of EBV-associated PAPL evolving
      from T-cell-rich lymphoid infiltration.

PMID- 8299099
TI  - UICC meeting on breast-cancer screening in pre-menopausal women in developed
      countries.

PMID- 8299100
TI  - Dietary strategies for cancer prevention.

PMID- 8299101
TI  - Prognostic factors of malignant mesothelioma of the pleura.

PMID- 8299102
TI  - Nausea induced by mental images of chemotherapy.

PMID- 8299103
TI  - Caffeine: how much is too much?
AB  - Too much caffeine can cause numerous physical and psychological symptoms of poor
      health. It could negatively affect reproduction and is suspected of causing some
      cancers. It can affect cardiovascular functioning, and can even produce symptoms
      similar to those of mental illness. Despite this broad range of known and
      suspected effects of caffeine, nurses rarely consider caffeine intake in initial
      nursing assessments of clients. They should.

PMID- 8299104
TI  - After the crime, before the trial.
AB  - The eighth-floor lounge of Calgary General Hospital's Forensic Unit affords an
      unimpeded view of the city's skyline. But behind its barless windows is a locked,
      high-security area housing individuals charged under the justice system. In most
      cases they are there for a 30-day psychiatric assessment to determine their
      fitness to stand trial for charges ranging from loitering to sexual assault to
      first degree murder. In all cases they are there for high quality psychiatric
      care provided by a multidisciplinary team, of which nurses are key members.

PMID- 8299105
TI  - The nurses are innocent.
AB  - In 1980-81, the nursing and medical staff of Toronto's Hospital for Sick Children
      (HSC) were agonizing over an increased death rate on cardiac wards 4A and 4B and
      groping for the cause. The key to this diagnostic puzzle appeared to surface when
      hospital radioimmunoassay tests revealed very high autopsy readings of digoxin on
      four babies who died during this period, Janice Estrella, Justin Cook, Kevin
      Pacsai and Allana Miller. Since one nursing team was present during each of these
      infants' final hours, it was assumed that one or more of the nurses had
      intentionally poisoned the infants with digoxin. A web of circumstantial evidence
      entrapped team member Susan Nelles, who was charged with murder.

PMID- 8299106
TI  - The environmental connection.
AB  - Both the World Health Organization and the Canadian Health for All concept
      recognize that healthy environments are fundamental to human health. Usually, the
      responsibility for environmental protection is assigned to public health
      inspectors. But there is more to a healthy environment than protection. Creating
      a healthy environment means "altering or adapting our social, economic and
      physical surroundings in ways that not only preserve but also enhance our
      health." Clearly, health promotion is an integral part of the concept. As experts
      in community health promotion, public health nurses (PHNs) could--and should-
      complement the work of health inspectors.

PMID- 8299107
TI  - [Caring].
AB  - Many nurse scientists consider caring to be the core concept of nursing practice.
      This article describes the caring process that occurs when a nurse and a client
      interact in a nursing care situation. This interactional process has five
      integrating phases: co-presence, experience-sharing, caring acts, caring
      perception, and mutual care-receiving. The authors provide a specific example
      that illustrates this caring process. The difficulties inherent in the caring
      process relate to one, or a combination of, three factors: the nurse, the client,
      and/or the circumstances. Nurses must be cognizant of the client's expression of
      subtle clues that indicate the need for caring. They also need to learn to
      recognize their own personal signals that might prevent them from engaging in the
      caring process. For caring, in its full context, can only occur when nurses know
      how to care for themselves. Nurses face unpredictability and challenges in their
      practice on a daily basis. In order to promote caring they must learn to promote
      an environment that nurtures this process. The authors discuss the essential
      characteristics of a favorable caring environment and present the conditions that
      can enhance quality nursing. The challenges that caring nurses face are
      counterbalanced by the value they attribute to this basic human need and the
      profound human benefits that caring brings.

PMID- 8299108
TI  - [To teach and to help the students to open up].
AB  - Nursing education in Canada is undergoing fundamental change. This will have
      profound effects on the new graduates' approach to practice. Currently, the
      greatest challenge for nurse educators is not only to develop nurses who can
      effectively work in a health care setting, but to prepare nurses who have the
      knowledge, strength and will to transform the health care system. The author
      reminds us that past educational practices, developed for the needs of men, had a
      negative impact on nursing education. This educational method neither encouraged
      dialogue nor the development of critical decision-making skills. The masculine
      model, with its rational/empirical focus, is still currently used in nursing
      research and practice. This model still exists even though nurses do not always
      face straightforward situations requiring "black or white" answers. The author
      maintains that nurse educators should review the traditional teaching methods and
      replace them with practices that humanize nursing care and encourage critical
      thinking. From this will emerge a renewed sense of dignity, empowerment, hope and
      independence both for the nurse and the patient.

PMID- 8299109
TI  - The nurse and the media.

PMID- 8299110
TI  - From a patient's perspective.

PMID- 8299111
TI  - Operation: happy holidays.
AB  - The Christmas holiday season is supposed to be a time of togetherness--a time
      with friends and family. But in most hospitals this is a time of disruption,
      loneliness and distress for both staff and patients. There are ways, however, to
      make the holiday season a more positive experience.

PMID- 8299112
TI  - Lawsuits and nurses.
AB  - As a health care professional, you are legally accountable for the nursing
      services you provide. This means you could be sued if a patient suffers harm
      while in your care, whether or not you were to blame.

PMID- 8299113
TI  - Curative effects of combination therapy with lentinan and interleukin-2 against
      established murine tumors, and the role of CD8-positive T cells.
AB  - The antitumor activity of a combination of an antitumor polysaccharide, lentinan
      (a beta 1-3 glucan with beta 1-6 branches), and interleukin-2 (IL-2) was
      evaluated against established MBL-2 lymphoma and S908.D2 sarcoma at i.d. sites.
      Treatment of the MBL-2-tumor-bearing BDF1 mice with lentinan and IL-2 induced
      complete regression of tumor in 87.5% of mice treated. In contrast, treatments
      using either lentinan or IL-2 alone failed to induce complete regression of
      tumor, although temporal growth inhibition of tumor was observed about in half of
      the mice treated. Improvements of antitumor effects by the combination of
      lentinan and IL-2 were also observed in the MBL-2/B6 and S908.D2/B10.D2 systems.
      Expression of the antitumor effects of lentinan/IL-2 treatments required the
      intact T cell compartment, because the effects were not observed when nude mice
      were used. In the MBL-2/B6 system, the antitumor action of lentinan/IL-2
      treatment was abolished in mice treated with antibody to CD8 antigen, whereas
      antibodies to CD4 or NK1.1 were ineffective. Furthermore, augmented tumor
      specific cytotoxic T lymphocyte (CTL) activity was observed in regional lymph
      node cells of the mice after lentinan and IL-2 administration. These data
      indicate that the antitumor effects of lentinan/IL-2 are mediated by CD8+ CTL but
      not by CD4+ T cells or NK1.1+ NK/LAK cells, and suggest that this combined
      therapy may be effective against even established tumors that are resistant to IL
      2 therapy.

PMID- 8299114
TI  - Liposome-encapsulated muramyl tripeptide up-regulates monocyte chemotactic and
      activating factor gene expression in human monocytes at the transcriptional and
      post-transcriptional levels.
AB  - Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a
      novel immune modulator that is now under investigation against metastatic
      melanoma and osteosarcoma. We have already reported that L-MTP-PE induced
      monocyte-mediated tumoricidal activity and up-regulation of the tumor necrosis
      factor and interleukin-1 (IL-1) in vivo and in vitro. We now demonstrate that L
      MTP-PE also induces monocyte chemotactic and activating factor (MCAF) mRNA
      expression at both the transcriptional and post-transcriptional levels. Monocyte
      chemotactic activity was also present in the supernatants of L-MTP-PE-stimulated
      cells. In monocytes, the increased expression of MCAF was induced rapidly (by 2
      h) but was short-lived. By 4 h, MCAF mRNA had decreased to background level. We
      found no change in MCAF mRNA levels in lymphocytes exposed to L-MTP-PE. We
      therefore conclude that L-MTP-PE selectively up-regulates MCAF expression in
      monocytes and that MCAF may play a role in the tumoricidal and immune-stimulating
      activity of L-MTP-PE.

PMID- 8299116
TI  - Macrophage and dendritic cell infiltration in head and neck squamous-cell
      carcinoma; an immunohistochemical study.
AB  - A study was undertaken to help us reach a better understanding of the tumor
      infiltrating pattern of lymphoid cells and in particular of monocyte-derived
      cells, namely the CD68+, acid-phosphatase-expressing scavenger macrophages and
      the MHC-class-II- and S100-antigen-presenting dendritic cells in head and neck
      squamous-cell carcinoma. In the stroma of the tumors distinctive small fields of
      lymphocytes were found, the T cell areas of these fields being intermingled with
      dendritic cells. Intra-epithelial dendritic cell infiltration was low. The
      infiltrative pattern of macrophages was similar to patterns described in earlier
      studies with substantial stromal invasion and inconsistent intra-epithelial
      invasion, but small granuloma-like structures of CD68+ macrophage-like cells,
      found in the stroma of tumors, have not been reported before. The histochemical
      localization of the tumor-infiltrated dendritic cells and macrophages supports
      the view that the former cells are involved in the sensitization to tumor
      antigens, whereas the latter cells are involved in tumor cytotoxicity/scavenging
      of tumor cell debris. Although it has been shown in the past that transmembranal
      (TM) factors (p15E-like factors) present in the serum and tumor of patients with
      cancer of the head and neck have suppressive effects on
      monocyte/macrophage/dendritic cell function, a relationship between the intensity
      of epithelial staining for TM factors and the infiltrative pattern of
      monocytes/macrophages/dendritic cells could not be demonstrated.

PMID- 8299115
TI  - Modification of monoclonal antibody carbohydrates by oxidation, conjugation, or
      deoxymannojirimycin does not interfere with antibody effector functions.
AB  - Site-specific attachment of metal chelators or cytotoxic agents to the
      carbohydrate region of monoclonal antibodies results in clinically useful
      immunoconjugates [Doerr et al. (1991) Ann Surg 214: 118, Wynant et al. (1991)
      Prostate 18: 229]. Since the capacity of monoclonal antibodies (mAb) to mediate
      tumor cell lysis via antibody-dependent cellular cytotoxicity (ADCC) or
      complement-dependent cytotoxicity (CDC) may accentuate the therapeutic
      effectiveness of immunoconjugates, we determined whether site-specific
      modification of mAb carbohydrates interfered with these functions. The chemical
      modifications examined consisted of periodate oxidation and subsequent
      conjugation to either a peptide linker/chelator (GYK-DTPA) or a cytotoxic drug
      (doxorubicin adipic dihydrazide). mAb-associated carbohydrates were also modified
      metabolically by incubating hybridoma cells in the presence of a glucosidase
      inhibitor deoxymannojirimycin to produce high-mannose antibody. All four forms
      (unaltered, oxidized, conjugated and high-mannose) of murine mAb OVB-3 mediated
      tumor cell lysis via CDC. Similarly, equivalent ADCC was observed with native and
      conjugated forms of mAb OVB-3 and EGFR.1. ADCC was achieved with different murine
      effector cells such as naive (NS), poly (I*C)- and lipopolysaccharide-stimulated
      (SS) spleen cells, or Corynebacterium-parvum-elicited peritoneal cells (PEC). All
      murine effector cell types mediated tumor cell lysis but differed in potency such
      that PEC > SS > NS. Excellent ADCC activity was also demonstrable by human
      peripheral blood mononuclear cells with OVB-3-GYK-DTPA and high-mannose OVB-3
      mAb. ADCC activity was detectable in vivo: both native and conjugated OVB-3
      inhibited growth of OVCAR-3 xenografts in nude mice primed with C. parvum. In
      conclusion, modification of mAb carbohydrates did not compromise their in vivo or
      in vitro biological functions. Therefore, combination therapy using
      immunomodulators to enhance the effector functions of site-specific
      immunoconjugates could be seriously contemplated.

PMID- 8299117
TI  - Combination therapy with a synthetic peptide of C-reactive protein and
      interleukin 2: augmented survival and eradication of pulmonary metastases.
AB  - A synthetic peptide (RS-83277) derived from the structure of human C-reactive
      protein (CRP) was previously shown to have antitumor activity in three different
      murine tumor models when administered in multilamellar vesicles (MLV). The
      therapeutic effects were comparable to those seen with MLV-encapsulated native
      CRP. The present study evaluated the therapeutic and immunomodulatory effects of
      administering CRP peptide RS-83277 MLV simultaneously with low-dose recombinant
      interleukin-2 (IL-2) to C57Bl/6 mice bearing established pulmonary metastases of
      fibrosarcoma T241. Results demonstrated that the capacity of RS-83277 MLV to
      inhibit tumor metastases and prolong survival was significantly augmented by
      combination with 10,000 U/day IL-2 i.p. Treated animals showed no evidence of
      toxicity. By immunohistochemistry, increased Thy 1.2+ cells were detectable in
      lungs of RS-83277 MLV/IL-2-treated animals compared to those receiving RS-83277
      MLV alone. Circulating tumor necrosis factor alpha (TNF) and interferon (IFN)
      were not detectable in animals receiving RS-83277 MLV alone, but TNF was
      significantly elevated in animals receiving IL-2. In the presence of combination
      therapy, however, circulating TNF was not detectable. Results suggest that the
      combination of synthetic CRP peptide RS-83277 MLV and low-dose IL-2 offers a
      therapeutic advantage over either agent alone.

PMID- 8299119
TI  - Poor induction of interleukin-2 receptor expression on CD8bright+ cells in whole
      blood cell cultures with CD3 mAb. Implications for immunotherapy with CD3 mAb.
AB  - To induce better stimulation of T cells during recombinant interleukin-2 (rIL-2)
      therapy of renal cell carcinoma patients, pretreatment with low-dose CD3
      monoclonal antibody (mAb) has been proposed. However, in our clinic, such a
      treatment did not induce additional activation of T cells. To investigate this we
      performed whole blood cell cultures with rIL-2 or CD3 mAb as a stimulant.
      Cultures using isolated blood mononuclear cells were used as a control. When
      stimulated by the addition of rIL-2, the lymphocyte composition and activation of
      whole blood cultures did not differ from those of mononuclear cell (MNC)
      cultures. However, when stimulation was performed with CD3 mAb, CD8bright+ cells
      in whole blood cultures were not or only minimally induced to express CD25 or IL
      2 receptor beta (IL-2R beta). This is in contrast to the situation found in MNC
      cultures where all CD8bright+ cells expressed CD25 or IL-2R beta to a high extent
      at the end of culture. When rIL-2 or recombinant interferon gamma (rIFN gamma)
      was added to whole blood cultures together with CD3 mAb, significantly more
      CD8bright+ cells were induced to express CD25 or IL-2R beta. These results
      suggest that whole blood cultures represent the in vivo situation better than MNC
      cultures. In addition, the results suggest that, also in vivo, administration of
      low-dose CD3 mAb alone might not be sufficient to induce IL-2R expression on
      CD8bright+ cells, and would therefore not induce additional specific T cell
      activation in rIL-2-based immunotherapy. The presented results suggest that in
      vivo simultaneous administration of rIFN gamma or rIL-2 with low-dose CD3 mAb
      might induce better stimulation of CD8+ T cells than CD3 mAb only.

PMID- 8299118
TI  - Requirement of monocytes and T-helper cells during development of tumor cell
      cytotoxicity in targeted T cells.
AB  - In cocultures of human placental alkaline phosphatase(PLAP)-positive MO4 tumor
      cells and human peripheral blood mononuclear cells (PBMC), also containing a
      heteroconjugate (7E8-OKT3) synthesized between the anti-PLAP monoclonal antibody
      7E8 and the anti-CD3 antibody OKT3, and supplemented with low levels of
      recombinant interleukin-2 (rIL-2), T cells are progressively activated, resulting
      in tumor cell lysis. To unravel the contribution of PBMC subsets to the
      generation of this targetable cytotoxicity, PBMC subsets were studied after their
      isolation by cell sorting, either from fresh PBMC or from PBMC pre-activated with
      OKT3 and rIL-2. Whereas no targetable cytotoxicity was found in Fc-receptor
      bearing CD3- cells, tumor cells were lysed by CD3+ T cells (mostly CD8+) isolated
      from pre-activated PBMC. When isolated from fresh PBMC, neither the CD8+ T cell
      subset, nor the total CD3+ T cell population developed significant targetable
      cytotoxicity, even in the presence of rIL-2. Thus, additional cell types are
      essential for the CD8+ T cell activation. Indeed, CD4+ T cells isolated from pre
      activated but not from fresh PBMC were capable of eliciting cytotoxicity in fresh
      CD8+ T cells. The non-targeted monocytes were found to be the activators of the
      CD4+ T cells. In summary, targeting T cells to the surface of a tumor cell is not
      sufficient per se to achieve activation and lysis. The progressive tumor cell
      lysis by targeted T cells seems to be initiated by non-targeted monocytes
      activating CD4+ T cells, these cells in turn promoting CD8+ T cell activation,
      necessary for the development of cytotoxicity.

PMID- 8299120
TI  - Soluble factors produced by macrophages/monocytes inhibit lymphokine-activated
      killer activity in rat splenocyte cultures.
AB  - In the present study we investigated the inhibition of interleukin-2(IL-2)
      induced lymphokine-activated killer (LAK) activity in rat splenocyte cultures in
      relation to the presence of 2-mercaptoethanol and macrophages/monocytes. The
      presence of 2-mercaptoethanol is necessary for induction of LAK activity in rat
      splenocyte cultures. Removal of macrophages/monocytes from rat splenocytes by
      plastic or nylon-wool adherence, or iron ingestion resulted in LAK induction by
      IL-2 in the absence of 2-mercaptoethanol. The effect of macrophages/monocytes on
      LAK activity was also studied in transwell co-cultures. In the absence of 2
      mercaptoethanol, the induction of LAK activity was very low in
      macrophage/monocyte-depleted splenocytes with macrophages/monocytes in the upper
      compartment of a transwell culture. In contrast, in the presence of 2
      mercaptoethanol a high level of LAK activity was induced in these transwell
      cultures, showing that 2-mercaptoethanol abolished the LAK-inhibiting capacity of
      macrophages/monocytes. In addition, established LAK activity was strongly
      inhibited when, after LAK induction, splenocytes were cultured with supernatant
      of unfractionated splenocytes, which were cultured with IL-2 but in the absence
      of 2-mercaptoethanol. Addition of 2-mercaptoethanol abrogated the inhibiting
      effect of the supernatant completely. These experiments demonstrate that rat
      macrophages/monocytes produce 2-mercaptoethanol-sensitive soluble LAK-inhibiting
      factors. Ultrafiltration of conditioned culture medium of macrophages/monocytes
      revealed the presence of LAK-inhibiting factors larger than 10 kDa. We concluded
      that 2-mercaptoethanol-sensitive soluble factors produced by
      macrophages/monocytes determine the level of LAK induction in rat splenocyte
      cultures.

PMID- 8299121
TI  - A high incidence of serum IgG antibodies to the Epstein-Barr virus replication
      activator protein in nasopharyngeal carcinoma.
AB  - The BamHI Z EBV replication activator (ZEBRA) protein is involved in the switch
      from latency to productive cycle of Epstein-Barr virus. A recombinant ZEBRA
      protein was synthesized and assessed in enzyme-linked immunosorbent assay (ELISA)
      for serum IgG response in nasopharyngeal carcinoma (NPC) patients. In 100 NPC
      serum samples that were positive for IgA to the EBV viral capsid antigen (VCA),
      75% had IgG anti-ZEBRA antibodies. In contrast, only 3/83 (3.6%) serum samples
      from healthy donors and 2/50 (4%) from other cancers were positive for IgG to
      ZEBRA. Interestingly, in a selected group of 100 NPC sera negative for IgA to
      VCA, 25% contained IgG anti-ZEBRA antibodies. This suggests that the ELISA for
      IgG anti-ZEBRA may also identify earlier cases of NPC not detected by the
      conventional immunofluorescence test for IgA to VCA.

PMID- 8299122
TI  - Cytotoxic susceptibility and defective MHC class I expression do not correlate
      with mutation of p53 in human carcinomas.
AB  - Twenty-nine samples of ex vivo ovarian and lung carcinomas were investigated for
      the relationship between the presence of mutated protein 53 (mp53) and cytotoxic
      susceptibility. Unaltered expression of MHC class I alleles was required for the
      cytotoxic susceptibility of tumour cells to the autologous ex vivo blood
      lymphocytes, i.e. all 4 sensitive tumours belonged to the group of 11 tumours
      without defect in MHC class I expression. In contrast, the susceptibility did not
      correlate with the presence of mp53, i.e. cases with mp53 were randomly
      distributed between the sensitive and resistant tumours (2/4 and 10/17
      respectively). There was no correlation either between the p53 mutation and down
      regulation of MHC class I alleles. The results suggest that in these tumours the
      mutated p53 is not the source of immunogenic peptides and that the lack of
      recognition of the tumours with mp53 is not caused by a defect in the expression
      of MHC class I molecules.

PMID- 8299124
TI  - An analysis of factors influencing psychosocial adjustment to cardiomyopathy.

PMID- 8299123
TI  - Increasing infiltration and activation of CD8+ tumor-infiltrating lymphocytes
      after eliminating immune suppressive granulocyte/macrophage progenitor cells with
      low doses of interferon gamma plus tumor necrosis factor alpha.
AB  - By secreting granulocyte/macrophage colony-stimulating factor (GM-CSF),
      metastatic Lewis lung carcinoma (LLC-LN7) tumors induce the appearance of
      myelopoiesis-associated immune-suppressor cells that resemble granulocytic
      macrophage (GM) progenitor cells. The presence of these GM-suppressor cells in
      mice bearing LLC-LN7 tumors was associated with a reduced capacity of splenic T
      cells to proliferate in response to interleukin-2 (IL-2). Administration of low
      doses of 100 U interferon gamma (IFN gamma) plus 10 U tumor necrosis factor alpha
      (TNF alpha) to the tumor bearers, a combination treatment that we previously
      showed to diminish the presence of GM-suppressor cells synergistically, restored
      proliferative responsiveness of the splenic T cells to IL-2. These LLC-LN7
      bearing mice were also examined for whether cells that phenotypically resemble GM
      progenitor cells (ER-MP12+ cells) infiltrate the tumor mass. ER-MP12+ cells
      composed approximately 10% of the cells isolated from dissociated tumors of mice
      that had been treated with placebo or with either IFN gamma or TNF alpha alone,
      but IFN gamma/TNF alpha therapy markedly reduced the number of tumor-infiltrating
      ER-MP12+ suppressor cells. The IFN gamma/TNF alpha treatment to eliminate GM
      suppressor cells and restore T cell responsiveness to IL-2 was next coupled with
      low dose IL-2 therapy (100 U twice daily). Addition of IL-2 to the treatment
      regimen did not significantly influence the effectiveness of the IFN gamma/TNF
      alpha treatment in eliminating GM-suppressor cells from the LLC-LN7 tumor mass.
      However, inclusion of IL-2 with the IFN gamma/TNF alpha treatment regimen
      enhanced the CD8+, but not the CD4+, cell content within the tumor, and
      diminished the number of metastatic lung nodules within the mice. When these
      tumors were excised, dissociated, and bulk-cultured with a low dose of IL-2, an
      increased level of cytotoxic T lymphocyte (CTL) activity was generated in the TIL
      cultures from mice that had received IFN gamma/TNF alpha plus IL-2 treatments. A
      lesser but detectable level of CTL activity was generated in TIL cultures from
      mice that were treated with only IFN gamma/TNF alpha, while no CTL activity was
      generated in tumor cultures from mice receiving only placebo or low-dose IL-2.
      These results suggest the effectiveness of IFN gamma plus TNF alpha therapy in
      restoring IL-2 responsiveness in mice bearing GM-suppressor cell-inducing tumors
      and at enhancing both the intratumoral CD8+ cell content and the generation of
      CTL activity in bulk cultures of these tumors.

PMID- 8299125
TI  - Universal precautions--are we there yet?

PMID- 8299126
TI  - Controversies involving the reimbursement of pins, posts, cores, build-ups, and
      copings.

PMID- 8299127
TI  - Scaling and root planing: its role in contemporary periodontal therapy.

PMID- 8299128
TI  - Posterior base repair to maximize complete denture retention.

PMID- 8299129
TI  - Acupuncture anesthesia/analgesia for pain and anxiety control in dental practice.
      Part 2: Techniques for clinical applications.

PMID- 8299130
TI  - A multicenter 5-year retrospective survival analysis of 6,200 Integral implants.

PMID- 8299131
TI  - Sports dentistry.

PMID- 8299132
TI  - Combining vital root retention and the osseointegrated implant to support a
      removable prosthesis.

PMID- 8299133
TI  - Dental management of the renal transplant patient.

PMID- 8299134
TI  - Choosing a retirement plan.

PMID- 8299135
TI  - The rotational path removable partial denture: the overlooked alternative.

PMID- 8299136
TI  - Current bibliography of cell calcium prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 8299137
TI  - Tetraethylammonium blockade of K+ channels in GH4C1 cells regulates prolactin
      secretion by inducing Ca2+ influx.
AB  - Tetraethylammonium (TEA), a K+ channel blocker, induced PRL secretion and an
      increase in cytosol Ca2+ concentration [Ca2+]i in a dose-dependent manner between
      5-20 mM in GH4C1 rat pituitary tumor-derived cells. Removal of medium Ca2+ or the
      addition of 1 microM nifedipine abolished both the induced [Ca2+]i increment and
      PRL secretion. TEA augmented the TRH-induced rise in [Ca2+]i and inhibited the
      rise in [Ca2+]i induced by 30 mM K+. The dynamics of TEA-, TRH- and K(+)-induced
      PRL secretion were different, with the TEA-induced secretory peak occurring at
      about 10 min compared to 2-3 min for TRH and K+. Tolbutamide, which blocks ATP
      sensitive K+ channels, induced PRL secretion without causing a rise in [Ca2+]i.
      The results suggest that: (a) K+ channels have a complex interaction with the PRL
      secretory process in GH4C1 cells; (b) TEA induces PRL secretion by causing Ca2+
      influx through dihydropyridine-sensitive Ca2+ channels; and (c) K+ channels play
      a different role in the [Ca2+]i rise induced by TRH than in that induced by
      depolarizing K+.

PMID- 8299138
TI  - Expression of Ca2+ binding proteins of the sarcoplasmic reticulum of striated
      muscle in the endoplasmic reticulum of pig smooth muscles.
AB  - The Ca2+ binding proteins in the lumen of intracellular Ca2+ stores differ
      between muscle and non-muscle cells, indicating a specific role of these proteins
      in intracellular Ca2+ regulation. Since smooth muscle cells possess both muscle
      and non-muscle characteristics, we have studied the presence and the differential
      expression of the muscle-type Ca2+ binding proteins--calsequestrin, sarcalumenin,
      and the histidine-rich Ca2+ binding protein (HCP)--in several smooth muscle
      tissues from the pig. Western blot analysis showed that among the smooth muscles
      studied, the cardiac isoform of calsequestrin is expressed at the highest levels
      in the stomach. Calsequestrin was present at lower levels in ileum and trachea,
      whereas this protein was undetectable in aorta and main pulmonary artery. The
      total amount of calsequestrin in the stomach was estimated to be 20-30-times
      lower than in the pig heart. Whereas calsequestrin from pig presented the same
      apparent M(r) in sodium dodecyl sulphate polyacrylamide gels as the well
      characterized protein from rabbit, the apparent M(r) of both sarcalumenin and HCP
      was lower in pig than in rabbit. The presence of HCP was demonstrated in pig
      stomach and ileum, while sarcalumenin was detected only in the stomach. These
      results demonstrate further biochemical differences between smooth muscle cells
      of large blood vessels and those of the digestive tract. The present findings on
      the differential distribution of muscle-type Ca2+ binding proteins are discussed
      in relation to biochemical and functional differences between these smooth muscle
      cells.

PMID- 8299140
TI  - Effect of calcium depletion on the secretion of newly synthesised human chorionic
      gonadotropin by first trimester human placenta.
AB  - Depletion of calcium in the extracellular medium used to incubate first trimester
      human placental minces resulted in a significant decrease in the quantity of
      immunoreactive hCG in the medium and a corresponding increase in the tissue. In
      contrast, when secretion of newly synthesised hCG was monitored in the absence of
      calcium by using a radioactive amino acid precursor, a significant increase in
      the secretion of newly synthesised hCG in the medium was noticed. This was true
      of secretion of other proteins also as evidenced by the increase in the
      trichloroacetic acid precipitable radioactivity in the medium in the absence of
      calcium. These results suggest that newly synthesised hCG is preferentially
      released over stored hormone in the absence of calcium.

PMID- 8299139
TI  - Heterogeneity of intracellular calcium responses to parathyroid hormone and
      thrombin in primary osteoblast-like cells and UMR106-01 cells: correlations with
      culture conditions, intracellular calcium concentration and differentiation
      state.
AB  - The present study evaluates the effect of parathyroid hormone (PTH) on
      intracellular calcium. Intracellular calcium ion concentrations ([Ca2+]i) in
      fetal rat osteoblasts in primary culture (ROB) and in UMR106-01 osteogenic
      sarcoma cells were monitored as changes in the ratio (R) of Fura-2 fluorescence
      intensities in single cells as well as populations of cells. In both single ROB
      and UMR106-01 cells, addition of 10(-7) M rat PTH1-34 and 3 NIH units/ml human
      thrombin resulted in heterogeneous responses in R values and therefore [Ca2+]i.
      PTH-induced calcium responsiveness of ROB was dependent on culture conditions,
      such that response frequencies were positively correlated with the percentage of
      fetal calf serum in the culture medium. PTH responsive ROB and UMR106-01 cells
      had significantly higher resting [Ca2+]i than unresponsive cells. PTH- or
      thrombin-mediated calcium signalling appeared not to be correlated to alkaline
      phosphatase activity in single ROB. Low percentages of cells responded to PTH in
      comparison to thrombin suggesting that an increase in [Ca2+]i is not a common PTH
      signalling pathway in osteoblasts in primary culture. Our data suggest that
      activation of this signalling pathway by PTH is culture condition dependent,
      possibly via a cell-cycle related increase in sensitivity of the pathway.

PMID- 8299141
TI  - Calmodulin expression during proliferative activation of human T lymphocytes.
AB  - We have investigated the levels of calmodulin mRNA species and calmodulin protein
      during proliferation of human T lymphocytes. Quiescent lymphocytes expressed the
      1.7 kb transcript of CaM I, the 1.4 kb of CaM II and the 2.3 kb of CaM III.
      Phytohaemagglutinin added to peripheral blood lymphocytes induced DNA replication
      which started at 48 h and reached a maximum at 72 h after activation. All the
      species of calmodulin mRNAs, including the 4.0 kb transcript of CaM I and the 0.8
      kb of CaM III which were not detected in quiescent cells, increased during
      lymphocyte proliferation. At 72 h after activation, the increase of CaM I and CaM
      II transcripts were found to be 2-fold whereas CaM III mRNAs increased 9-fold.
      The cellular content of calmodulin protein was also found to increase during
      proliferation and calmodulin accumulations in cytosol and nuclei of activated
      cells were observed. Two calmodulin binding proteins of 180 and 170 kD were found
      to increase in the nuclei of proliferating lymphocytes, whereas on the contrary 3
      other calmodulin binding proteins of 110, 62 and 60 kD decreased during
      proliferation.

PMID- 8299142
TI  - Nimodipine: a calcium-entry-blocker or a calcium-entry-regulator?

PMID- 8299143
TI  - Regulation of microtubule dynamic instability.
AB  - Characterization of microtubule assembly in vivo and in vitro has raised
      questions of how cells regulate dynamic instability. While dynamic instability is
      an intrinsic property of the tubulin molecule, factors are required to increase
      the plus-end elongation rate and increase the frequencies of both catastrophe and
      rescue to achieve cellular tubulin turnover rates. It is likely that the
      activities of the transition frequency regulators are themselves regulated during
      the cell cycle, but the mechanisms of regulation are not known. As we identify
      the proteins which alter microtubule assembly, new classes of MAPs will emerge.
      An understanding of how these proteins function may provide further insight into
      how cells organize the different arrays of microtubules used for such processes
      as vesicle transport, polarized organization of organelles, and chromosome
      movement.

PMID- 8299144
TI  - Unambiguous classification of microtubule-ends in vitro: dynamic properties of
      the plus- and minus-ends.
AB  - To understand the mechanism of dynamic instability of microtubule growth and
      shortening, one needs a means of reliably determining the polarity of the
      microtubules under investigation. Sea urchin sperm-tail axonemal fragments
      nucleate the growth of both plus-ended and minus-ended microtubules, but their
      polarity is not apparent by video-enhanced DIC microscopy. The polarity of a
      microtubule is usually assessed by observing differences between the rates and
      lengths of growth and shortening excursions of the two ends. In practice, though,
      a significant fraction of the population of microtubules displays characteristics
      intermediate between the average characteristics of either end, thereby escaping
      classification. Excluding these "intermediate" microtubules from the measured
      populations introduces bias into the understanding of microtubule dynamic
      instability. We circumvent this problem by making use of the plus-end directed
      movement of the microtubule-dependent molecular motor kinesin to determine the
      polarity of any given microtubule unambiguously. Carboxylated-microspheres coated
      with kinesin, which are clearly visible by DIC microscopy, were used to determine
      the polarity of a microtubule. The dynamics were then observed. Kinesin was found
      to have no marked effect on dynamic instability. By this technique, we show that
      the distributions of properties that describe microtubule dynamic instability
      (rates and lengths of growth and shortening as well as frequencies of
      interconversion between these phases) of plus-ends overlap to a significant
      extent with those of minus-ends. It is this overlap that obscures the usual
      classification of the ends. Therefore, models describing microtubule dynamic
      instability need to incorporate the broad and overlapping range of properties of
      the two ends.

PMID- 8299145
TI  - Smooth muscle myosin subfragment-1 is a kinetic analogue for heavy meromyosin in
      the extended conformation.
AB  - The 10S-->6S (Flexed-->Extended) transition in smooth muscle myosin is related to
      increased ATPase activity, but there is controversy over whether the analogous 9S
      ->7S transition in HMM is also associated with ATPase activity. We therefore
      studied the association of ionic strength, phosphorylation, and ATPase activity
      for HMM as compared to S1 which has no apparent flexed conformation. In addition,
      we performed both steady state and single turnover analyses, to control for
      artifacts due to multiple subfragment populations that might skew steady state
      results. At low ionic strength where myosin and HMM are in the flexed
      conformation, HMM had a near zero ATPase activity while S-1 had a high ATPase
      rate (0.07 s-1). At 400 mM ionic strength, where both myosin and HMM are in the
      extended conformation, S1 and HMM had the same ATPase rate (0.04 s-1).
      Phosphorylation did not affect S1 significantly, but shifted the HMM curve to
      higher rates at lower ionic strengths. Both steady state and single turnover
      experiments gave the same results, indicating that steady state results were not
      skewed by multiple subfragment populations. These data indicate that HMM has a
      conformation-ATPase relation similar to that observed with myosin. Furthermore,
      these findings suggest that the S1 ATPase rate corresponds to that of HMM in the
      extended conformation.

PMID- 8299146
TI  - Contractile protein dynamics of myofibrils in paired adult rat cardiomyocytes.
AB  - The purpose of this study was to determine how quickly contractile proteins are
      incorporated into the myofibrils of freshly isolated cardiomyocytes and to
      determine whether there are regions of the cells that are more dynamic than
      others in their ability to incorporate the proteins. Paired cardiomyocytes joined
      at intercalated discs and single cells were isolated from adult rats, and
      microinjected 3 hours later with fluorescently labeled actin, alpha-actinin,
      myosin light chains and vinculin. The cells were fixed and permeabilized at
      various period, 5 seconds and longer, after microinjection. Actin became
      incorporated throughout the I-Bands in as short a time as 5 seconds. The free
      edges of the cells, which were formerly intercalated discs, exhibited
      concentrations of actin greater than that incorporated in the I-Bands. This extra
      concentration of actin was not detected, however, at intact intercalated discs
      connecting paired cells. Alpha-actinin was incorporated immediately into Z-Bands
      and intercalated discs. Vinculin, also, was localized at the Z-Bands and at
      intercalated discs, but in contrast to alpha-actinin, there was a higher
      concentration of vinculin in the region of the intact intercalated discs. Both
      alpha-actinin and vinculin were concentrated at the free ends of the cells that
      were formerly parts of intercalated discs. Myosin light chains were observed to
      incorporate into the A-Bands in periods as short as 5 seconds. These results
      suggest that the myofibrils of adult cardiomyocytes may be capable of rapid
      isoform transitions along the length of the myofibrils. The rapid accumulation of
      fluorescent actin, alpha-actinin, and vinculin in membrane sites that were
      previously parts of intercalated discs, may reflect the response to locomotory
      activity that is initiated in these areas as cells spread in culture. A similar
      response after an injury in the intact heart could allow repair to occur.

PMID- 8299147
TI  - Neurofilaments move apart freely when released from the circumferential
      constraint of the axonal plasma membrane.
AB  - Squid giant axons were used to obtain axonal cytoskeletons that had been
      separated from the confines of their plasma membranes. To remove the plasma
      membrane, axoplasm was extruded from the giant axon directly into an artificial
      axoplasm solution (AAS). This procedure produces a smooth axoplasmic cylinder in
      which neurofilaments (NFs) are the most prevalent cytological elements. The NFs
      scatter light strongly and thus dark-field light microscopy can be used to
      quantify the volume occupied by these polymers. Measurements of the widths of the
      dark-field images of the axoplasmic cylinders showed that the cross-sectional
      area of the NF population increased by 60-110% (n = 8) between 1-100 min after
      plasma membrane removal, and then continued to increase more slowly for many
      hours. After 1,000 min, the cross-sectional area was 75-160% (n = 8) larger than
      at 1 min. These light microscopic measurements of axoplasm suggest that the NF
      population disperses to occupy a continuously increasing volume after removal of
      the plasma membrane and immersion in AAS. This inference was confirmed by
      quantitative ultrastructural studies of NFs in axoplasmic cross-sections, which
      demonstrated that the spacing between the NFs increased between 1-1,000 min after
      plasma membrane removal. Comparison of the NF density distribution after 1,000
      min with a theoretical distribution calculated using the Poisson theorem
      indicated that the NFs dispersed randomly. These studies on NFs in isolated
      axoplasm suggest that ordinary thermal forces of Brownian motion are sufficient
      to move axonal NFs apart independently and thereby to disperse them. We propose
      that, in the intact axon, the dispersive movements of the NFs spread the NF
      cytoskeleton radially and expansively to fill out the cylindrical space contained
      by the axonal plasma membrane and its surrounding connective tissue elements.

PMID- 8299148
TI  - Assembly dynamics of actin in adherent human neutrophils.
AB  - We have extended our previous studies of adherent neutrophils and compared actin
      depolymerization and intracellular calcium changes induced by adherence to
      laminin and fibronectin. In order to accurately assess cellular actin changes, F
      actin depolymerization in the cell lysates must be inhibited. We found that
      phalloidin or 3.7% formaldehyde treatment effectively inhibited the
      depolymerization of F-actin fragments following cell lysis. Formaldehyde and
      phalloidin treatment reduced G-actin levels 75-80% in suspended cells, 35-73% in
      cells adherent for 1 min, and about 50% for cells adherent for 3 min. When the
      actin was fixed, there were highly significant differences in G-actin levels
      between the suspended and adherent cells as compared with unfixed cells. Adhesion
      to both laminin and fibronectin initiated a rapid rise in G-actin with a
      corresponding decrease in F-actin. However, the changes were more pronounced in
      cells adherent to laminin. The peak of depolymerization occurred by 1 min and,
      thereafter, G-actin decreased and F-actin increased reaching a steady state at 5
      min. Adhesion to both laminin- and fibronectin-coated surfaces was accompanied by
      an increase of [Ca2+]i with a peak at 3 min, followed by a decrease from 3-5 min
      and a steady state attained between 5 and 10 min. The rise of [Ca2+]i in laminin
      adherent cells was about twice that in fibronectin-adherent cells at 3 min (P <
      0.02). Pertussis toxin, H-7, and staurosporin treatments did not alter the
      dynamic changes of actin in adherent cells, suggesting that these metabolic
      events are transduced by a G-protein and Protein Kinase C independent
      mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299149
TI  - Self-diploidization in Saccharomyces cerevisiae kar2 heterokaryons.
AB  - Zygotes isolated by micromanipulation from crosses of Saccharomyces cerevisiae
      strains, one of which carries a kar mutation, give rise most frequently to
      cytoductant colonies showing the nuclear constitution of either one of the two
      haploid parental strains. In crosses of kar2-1 strains to wild-type, about 10% of
      the cytoductants of both mating types are homozygous autodiploids. There is
      evidence indicating that self-diploidization occurs by fusion between sibling
      nuclei in the heterokaryotic zygote. Here we describe this phenomenon and propose
      to take advantage of it for the construction of genotypically-defined diploids
      able to mate, and of polyploid strains, which are useful tools in genetic and
      cytological studies.

PMID- 8299150
TI  - Pentose-phosphate pathway in Saccharomyces cerevisiae: analysis of deletion
      mutants for transketolase, transaldolase, and glucose 6-phosphate dehydrogenase.
AB  - Deletion mutants for the yeast transketolase gene TKL1 were constructed by gene
      replacement. Transketolase activity was below the level of detection in mutant
      crude extracts. Transketolase protein could be detected as a single protein band
      of the expected size by Western-blot analysis in wild-type strains but not in the
      deletion mutant. Deletion of TKL1 led to a reduced but distinct growth in
      synthetic medium without an aromatic amino-acid supplement. We also isolated
      double and triple mutants for transketolase (tkl1), transaldolase (tal1), and
      glucose 6-phosphate dehydrogenase (zwf1) by crossing the different mutants. A
      tal1 tkl1 double mutant grew nearly like wild-type in rich medium. Only the tkl1
      zwf1 double and the tal1 tkl1 zwf1 triple mutant grew more slowly than the wild
      type in rich medium. This growth defect could be partly alleviated by the
      addition of xylulose but not ribose. The triple mutant still grew slowly on a
      synthetic mineral salts medium without a supplement of aromatic amino acids. This
      suggests the existence of an alternative but limited source of pentose phosphates
      and erythrose 4-phosphate in the tkl1 zwf1 double mutants. Hybridization with low
      stringency showed the existence of a sequence with homology to transketolase,
      possibly a second gene.

PMID- 8299151
TI  - The ogd1 and kgd1 mutants lacking 2-oxoglutarate dehydrogenase activity in yeast
      are allelic and can be differentiated by the cloned amber suppressor.
AB  - The activity of mitochondrial 2-oxoglutarate dehydrogenase in S. cerevisiae can
      be impaired either by the ogd1 or the kgd1 mutation. The OGD1 gene and two
      suppressor genes were isolated by complementation of the ogd1 mutant. The
      complementation of the kdg1 mutant by the OGD1 gene, an allelism test, and
      meiotic mapping, revealed that the ogd1 and kgd1 mutations are allelic. The two
      mutations were differentiated by the cloned suppressor gene which was able to
      partially complement ogd1, but not kgd1. The molecular analysis of the suppressor
      gene revealed its identity with the natural tRNA(GlnCAG) gene found in the
      upstream region of URA10.

PMID- 8299152
TI  - Transcript accumulation of the GGP1 gene, encoding a yeast GPI-anchored
      glycoprotein, is inhibited during arrest in the G1 phase and during sporulation.
AB  - The GGP1 (GAS1) gene encodes an exocellular 115-kDa glycoprotein (gp115) of the
      yeast Saccharomyces cerevisiae. We have monitored the changes in GGP1 mRNA levels
      under different conditions of G1 arrest. Transcript levels rapidly decrease
      during transition from exponential growth to stationary phase. They also decrease
      in the ts cdc25 and cdc28 START mutants when brought to the restrictive
      temperature. In cells arrested in G1 by alpha F treatment, the GPP1 mRNA level
      undergoes a threefold reduction. During release from the G1 block the mRNA level
      rapidly increases with a maximum at the onset of budding. During sporulation GGP1
      mRNA level steadily decreases. These results indicate that the accumulation of
      the GGP1 transcript is inhibited during arrest in the G1 phase and during entry
      into the differentiative pathway of meiosis and sporulation. The induction of
      expression upon entry into the mitotic cycle suggests that GGP1 could be one of
      the genes whose transcription is activated at START.

PMID- 8299153
TI  - Regulation of Saccharomyces cerevisiae catalase gene expression by copper.
AB  - Treatment of Saccharomyces cerevisiae cells with copper induces the activity of
      Cu/Zn superoxide dismutase (SOD) and catalase. To understand the level at which
      Cu regulates catalase, the expression of the S. cerevisiae CTA1 (encoding the
      peroxisomal catalase A) and CTT1 (encoding the cytosolic catalase T) genes was
      monitored as a function of Cu treatment. Copper was found to specifically induce
      transcription of CTT1, but not CTA1, mRNA. Moreover, genetic and biochemical
      studies demonstrate that this induction is independent of the ACE1 Cu trans
      activator controlling the expression of yeast Cu/Zn SOD and metallothionein
      genes. Copper regulation of CTT1 thus appears to represent a novel metal
      regulatory pathway in S. cerevisiae cells.

PMID- 8299154
TI  - Promoter analysis of the bli-7/eas gene.
AB  - Expression of the Neurospora crassa gene bli-7, (identical with eas, and ccg-2),
      is induced by blue light, as well as glucose- or nitrogen-starvation. A promoter
      analysis was performed by an assay that does not involve promoter-reporter
      constructs but rather the insertion of foreign DNA into the transcribed sequence.
      To detect regulatory elements a series of deletions in the upstream region was
      generated. The inducibility of the gene, in response to the three inducing
      conditions mentioned, is lost by eliminating the region between -1498 bp and 
      1017 bp upstream of the transcription start point. A segment with an apparently
      negative effect was found between -595 bp and -429 bp, as well as a stretch of
      DNA from -429 bp to -380 bp which may exert a positive influence after light
      induction.

PMID- 8299155
TI  - Regional sequence homologies in starch-degrading enzymes.
AB  - The enzymatic hydrolysis of starch, consisting of linear (amylose) and branched
      (amylopectin) glucose polymers, is catalyzed by alpha-, beta- and glucoamylases
      (gamma-amylases), cyclodextrinases, alpha-glucosidases, and debranching enzymes.
      Saccharomyces cerevisiae cannot utilize starch. Our laboratory has previously co
      expressed the Bacillus amyloliquefaciens alpha-amylase (AMY) and the
      Saccharomyces diastaticus glucoamylase (STA2) genes in S. cerevisiae. A gene
      encoding a debranching enzyme (pullulanase) from Klebsiella pneumoniae ATCC15050
      was cloned and its nucleotide sequence determined. This gene will be co-expressed
      with the alpha- and gamma-amylase to produce an amylolytic S. cerevisiae strain.
      Extensive data base comparisons of the K. pneumoniae pullulanase amino-acid
      sequence with the amino-acid sequences of other debranching enzymes and alpha-,
      beta- and gamma-amylases (from bacteria, yeasts, higher fungi and higher
      eukaryotes), indicated that these debranching enzymes have amino-acid regions
      similar to those found in alpha-amylases. The conserved regions in alpha-amylases
      comprise key residues that are implicated in substrate binding, catalysis, and
      calcium binding and are as follows. Region 1: DVVINH; region 2: GFRLDAAKH and
      region 4: FVDNHD. When comparing conserved regions, no similarity could be
      detected between debranching enzymes and beta- and gamma-amylases.

PMID- 8299156
TI  - Induction of glucose oxidase, catalase, and lactonase in Aspergillus niger.
AB  - The induction of glucose oxidase, catalase, and lactonase activities was studied
      both in wild-type and in glucose oxidase regulatory and structural mutants of
      Aspergillus niger. The structural gene for glucose oxidase was isolated and used
      for Northern analysis and in transformation experiments using various gox
      mutations. Wild-type phenotype could be restored in the glucose oxidase-negative
      mutant (goxC) by transformation with the structural gene. We conclude, therefore,
      that the goxC marker which is located on chromosome 2 represents the structural
      gene of glucose oxidase. Glucose and a high oxygen level are necessary for the
      induction of all three enzyme activities in the wild-type strain and it was shown
      that both glucose and oxygen effects reflect regulation at the transcriptional
      level. The goxB mutation results in constitutive expression of all three
      activities although modulated to some extent by the carbon source. The goxE
      mutation only has an effect on lactonase and glucose oxidase expression and does
      not relieve the necessity for a high oxygen level. Catalase and lactonase could
      not be induced in the glucose oxidase-negative strain (goxC). Addition of H2O2
      resulted in the induction of all three enzymes in the wild-type without glucose
      being present. The H2O2 induction is probably mediated by the goxB product.
      Besides the H2O2 induction there is still an effect of the carbon source on the
      induction. A model for induction of glucose oxidase, catalase, and lactonase in
      A. niger is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299157
TI  - Randomly amplified polymorphic DNAs assess recombination following an induced
      parasexual cycle in Penicillium roqueforti.
AB  - Random amplified polymorphic DNAs (RAPDs) were used as a genetic marker system to
      characterize recombinant strains following the parasexual cycle of Penicillium
      roqueforti. After protoplast fusion and haploidization of diploid hybrids,
      segregants characterized by a reassortment of the parental genetic markers
      displayed specific RAPD fingerprints. The appearance or the loss of RAPD
      fragments demonstrate that these markers provide an efficient method to analyze
      recombination and to characterize somatic hybrids.

PMID- 8299158
TI  - Targeted integration into the Acremonium chrysogenum genome: disruption of the
      pcbC gene.
AB  - The cephalosporin C-producing fungus Acremonium chrysogenum was transformed to
      hygromycin B resistance using different vector constructs. These constructs
      contain sequences of the pcbC gene from A. chrysogenum, encoding isopenicillin N
      synthetase. Detailed analysis of transformants, including pulsed-field gel
      electrophoresis (PFGE), suggests that integration of multiple vector copies takes
      place predominantly via non-homologous integration. By increasing the length of
      vector-DNA homologous to genomic DNA, integration occurs more frequently into
      chromosome VI, carrying the endogenous pcbC gene copy. In gene disruption
      experiments, the length of vector homology required to obtain cephalosporin C
      minus transformants was investigated. Inactivation of the pcbC gene was observed
      only when homologous fragments of more than 3.0 kb were used on both sites of the
      resistance cassette. Southern analysis indicated homologous, as well as
      heterologous, integration of recombinant DNA. The integration of multiple vector
      copies leads to the appearance of truncated pcbC transcripts.

PMID- 8299159
TI  - Nucleotide sequence relationships of double-stranded RNAs in flax rust,
      Melampsora lini.
AB  - Flax rust, Melampsora lini strain SP6, contains 11 double-stranded (ds) RNA
      molecules with a total length of about 25 kbp. The dsRNAs are inherited in three
      genetic units: the L unit comprising a single 5.2 kbp dsRNA and contained within
      a 40-nm virus-like particle, and the A and B units each consisting of five dsRNAs
      (A1-A5, and B1-B5) ranging in size from 1.2 to 2.7 kbp. This paper reports the
      isolation of a cDNA library representing 10 of the 11 dsRNAs. By nucleic-acid
      hybridization techniques it has been shown that all ten sequences are unique
      showing no detectable cross-hybridization with any other dsRNA present in the
      rust. A near full-length sequence of 1932 bp of the B3 dsRNA is reported and
      contains several open reading frames, the largest of which comprises most of the
      molecule.

PMID- 8299160
TI  - psbD sequences of Bumilleriopsis filiformis (Heterokontophyta, Xanthophyceae) and
      Porphyridium purpureum (Rhodophyta, Bangiophycidae): evidence for polyphyletic
      origins of plastids.
AB  - The nucleotide sequences of the plastidal psbD genes of Bumilleriopsis filiformis
      and Porphyridium purpureum (encoding the D2 protein of photosystem II) are
      reported in this paper. The Bumilleriopsis sequence clusters together with
      Porphyridium when a most parsimonious protein tree of D2 sequences is
      constructed. A composite D1/D2 protein-similarity network reveals that neither
      the three red algal sequences nor the two heterokontophyte sequences
      (Bumilleriopsis, xanthophytes and Ectocarpus, phaeophytes) group together.
      Therefore, the Heterokontophyta and Rhodophyta may be heterogeneous groups.
      Instead, it emerges that the D1/D2 proteins of Porphyridium and Bumilleriopsis
      clearly form a tight cluster. D1 and D2 proteins apparently do not provide a
      reliable molecular clock. These results fit into hypotheses proposing a
      polyphyletic origin for complex plastids, even among the supposedly "natural"
      group of heterokontophytes.

PMID- 8299161
TI  - The ribosomal RNA repeats are non-identical and directly oriented in the
      chloroplast genome of the red alga Porphyra purpurea.
AB  - A detailed restriction map of the chloroplast genome of the red alga Porphyra
      purpurea has been constructed. Southern hybridization experiments with cloned or
      gel-purified restriction fragments and PCR products indicate that the P. purpurea
      chloroplast genome is approximately 188 kb in size. This circular molecule
      contains two rRNA-encoding repeats (approximately 4.9 kb) that separate the
      genome into single-copy regions of 34 kb and 144 kb. Interestingly, these repeats
      are arranged in a direct orientation. In addition, DNA sequencing of the ends of
      both repeats revealed that the two rRNA repeats are not identical. No
      intramolecular recombination between the repeats can be detected. We discuss the
      possibility that the chloroplast genome of P. purpurea is organized like that of
      the ancestral chloroplast.

PMID- 8299162
TI  - Use of reporter genes for the isolation and characterisation of different classes
      of sporulation mutants in the yeast Saccharomyces cerevisiae.
AB  - Reporter genes consisting of sporulation-specific promoters fused to lacZ were
      used as markers to monitor the sporulation pathway of the yeast Saccharomyces
      cerevisiae. Strains transformed with these lacZ gene fusions expressed beta
      galactosidase (assayable on plates using the substrate 5-bromo-4-chloro-3-indolyl
      beta-D-galactopyranoside, X-gal) in a sporulation-dependent manner. Mutagenesis
      experiments performed on transformed strains resulted in the recovery of a number
      of novel sporulation mutants. Three classes of mutants were obtained: those which
      overexpressed the reporter gene under sporulation conditions, those which did not
      express the gene under any conditions, and those which expressed the gene in
      vegetative cells not undergoing sporulation. On the basis of the blue colony
      colour produced in the presence of X-gal these have been described as superblue,
      white, and blue vegetative mutants, respectively. These were further
      characterised using earlier reporter genes and other marker systems. This study
      established that the multicopy reporter plasmids chosen do not interfere with
      sporulation; they are valid tools for monitoring the pathway and they provide a
      way to isolate mutations not readily selected by other markers.

PMID- 8299163
TI  - Parameters affecting lithium acetate-mediated transformation of Saccharomyces
      cerevisiae and development of a rapid and simplified procedure.
AB  - We have compared a number of procedures for the transformation of whole cells of
      the yeast Saccharomyces cerevisiae and assessed the effects of dimethylsulphoxide
      (DMSO) or ethanol, both of which have been reported to enhance transformation
      efficiency. We find that simplified methods benefit from the addition of one of
      these compounds, and although differences are observed between strains as to the
      more beneficial reagent, peak transformation efficiency is, in general, obtained
      with 10% DMSO or 10% EtOH. Increases of between six- and 50-fold are observed,
      despite a reduction in cell viability, and at this concentration the two
      compounds are not additive in their effects. The optimum level appears to depend
      on a balance between improved DNA uptake and reduced cell viability. As a result
      of this work we present a straightforward and rapid transformation procedure.

PMID- 8299164
TI  - Physical mapping of the MEL gene family in Saccharomyces cerevisiae.
AB  - Nine members, MEL2-MEL10, of the MEL gene family coding for alpha-galactosidase
      were physically mapped to the ends of the chromosomes by chromosome
      fragmentation. Genetic mapping of the genes supported the location of all the MEL
      genes in the left arm of their resident chromosomes.

PMID- 8299165
TI  - Isolation of a mutant allele that deregulates the threonine biosynthesis in
      Saccharomyces cerevisiae.
AB  - We have cloned the yeast allele HOM3-R2, that codes for a mutant aspartate kinase
      which is insensitive to feedback inhibition by threonine, by gap-repair. A strain
      carrying this allele in a multicopy plasmid, or integrated into the genome,
      accumulates 14-times and 8-times more threonine than the wild-type, respectively.
      The sequence of the mutant allele differs from that of the wild-type in a single
      base pair change, namely a G by an A, at position 1355 in the open reading frame.
      The fact that the presence of this mutant allele in a cell induces threonine
      overproduction points to aspartate kinase as the key enzyme in the regulation of
      threonine biosynthesis in yeast.

PMID- 8299166
TI  - Regulation of the ADE2 gene from Saccharomyces cerevisiae.
AB  - Regulation of ADE2 gene expression was investigated in the yeast S. cerevisiae
      using translational fusions between this gene and the lacZ gene from E. coli.
      Expression was repressed in the presence of adenine and slightly increased under
      amino-acid starvation conditions. The promoters of the ADE2 gene, and of other
      genes involved in adenine biosynthesis, contain the hexanucleotide sequence
      TGACTC. A search for the hexanucleotide TGACTC in yeast promoter sequences
      revealed that many genes not related to amino-acid biosynthesis contain such
      sequences. We show here that these elements play a crucial role in ADE2
      regulation since mutations in two such elements drastically reduced gene
      expression. Maximal expression required the transcriptional activators Bas1, Bas2
      and Gcn4, whereas Yap1 had only minor effects.

PMID- 8299167
TI  - Interaction of excision repair gene products and mitotic recombination functions
      in yeast.
AB  - We have tested the ability of mutants of three additional genes in the excision
      repair pathway of Saccharomyces cerevisiae to suppress the hyper-recombination
      and rad52 double-mutant lethality phenotypes of the rad3-102 (formerly rem1-2)
      mutation. Such suppression has previously been observed with mutant alleles of
      RAD1 and RAD4. We had hypothesized that the rad3-102 mutation created elevated
      levels of DNA lesions which could be processed by the products of the RAD1 and
      RAD4 genes into recombinogenic double-strand breaks requiring the RAD52 product
      for repair. In this report, we show that the RAD2, RAD7, and RAD10 genes are also
      necessary for this processing. We discuss our observations of varying levels of
      mitotic crossing-over in Rem- rad double-mutant strains.

PMID- 8299168
TI  - Transport properties of a C. albicans amino-acid permease whose putative gene was
      cloned and expressed in S. cerevisiae.
AB  - Using a gene bank of C. albicans, the lysine-permease deficiency in a strain of
      S. cerevisiae was complemented, and the restriction map of the corresponding C.
      albicans DNA fragment was constructed. Its expression in S. cerevisiae showed
      that the permease of C. albicans actively transports arginine (KT = 18 mumol/l,
      Jmax = 26 nmol/min per mg dry weight), lysine (KT = 12 mumol/l, Jmax = 18
      nmol/min per mg dry weight), histidine (KT = 37 mumol/l, Jmax = 9.7 nmol/min per
      mg dry weight), as well as their toxic analogues canavanine and thialysine, with
      high affinity. The intracellular concentration of basic amino acids transported
      into S. cerevisiae by the C. albicans permease reaches more than a thousand-times
      higher value compared to the external concentration in the medium. Accumulated
      amino acids do not leave the cells. The uptake is strongly reduced by the
      protonophores and inhibitors of plasma membrane H(+)-ATPase.

PMID- 8299169
TI  - Cloning and manipulation of the Schizosaccharomyces pombe his7+ gene as a new
      selectable marker for molecular genetic studies.
AB  - We have cloned the his7+ gene of the fission yeast Schizosaccharomyces pombe by
      complementation of the recessive mutant allele his7-366. The his7+ gene is able
      to complement a mutation of the Escherichia coli hisI gene, suggesting that his7+
      encodes a phosphoribosyl-AMP cyclohydrase. Subcloning experiments localize the
      gene to a 1.9-kb XbaI-BglII fragment. We describe the construction of plasmids to
      facilitate the use of his7+ as a selectable marker in S. pombe studies. Plasmid
      pEA2 carries his7+ cloned into the pUC18 polylinker. From either pEA2 or the
      original his7+ clone, pMN1, fragments carrying his7+ can be isolated using a
      variety of restriction enzymes for the construction of gene disruptions. Plasmid
      pEA500 is a cloning vector that carries his7+ and ars1, yet retains the ability
      to use the blue/white color screen to identify recombinants.

PMID- 8299170
TI  - An electrophoretic karyotype of the cultivated mushroom--Agaricus bisporus.
AB  - Thirteen chromosomal-sized DNA bands of the cultivated mushroom Agaricus bisporus
      have been resolved using the method of clamped homogeneous electric field (CHEF)
      electrophoresis. Using chromosome size standards from Schizosaccharomyces pombe,
      Saccharomyces cerevisiae and Candida albicans, the estimated size of the
      chromosomal DNAs ranged from 3.5 to 1.2 megabase pairs (Mb). By Southern
      hybridization with homologous gene probes, the chromosomal location of cellulase
      and laccase genes have been mapped. In addition, rDNA has been assigned to
      chromosomal bands using a heterologous gene probe. Genomic rearrangement is
      suggested in the commercial heterokaryon, as indicated by the presence of non
      comigrating homologous chromosomes, identified by a number of probes for
      particular DNA sequences.

PMID- 8299171
TI  - Electrophoretic karyotypes and gene mapping in eight species of the Fusarium
      sections Arthrosporiella and Sporotrichiella.
AB  - Pulsed-field gel electrophoresis was used to identify karyotypes for eight
      species of the Fusarium sections Arthrosporiella and Sporotrichiella. The total
      number of chromosome-sized DNA molecules varied from six to nine, depending on
      the species. The sizes of chromosomes ranged from 0.4 to approximately 6.5 Mb
      which gave estimates of genome size of between 27.0 and 29.9 Mb. When
      fractionated chromosomes of the eight species were probed with Tox5, a gene
      coding for the key-enzyme of trichothecene biosynthesis, strong hybridization
      signals developed in F. poae and F. sporotrichioides, suggesting that of the
      eight species examined only these two have the genetic potentiality to produce
      trichothecene mycotoxins. By using heterologous probes from Aspergillus different
      rRNA loci have also been mapped on Fusarium chromosomes.

PMID- 8299172
TI  - De-novo generation of mitochondrial DNA plasmids following cytoplasmic
      transmission of a degenerative disease in Ophiostoma novo-ulmi.
AB  - A mitochondrial DNA plasmid was detected in an isolate of Ophiostoma novo-ulmi
      with a degenerative disease. The DNA plasmid was shown to be derived from the
      mitochondrial DNA and to map to a region corresponding to the large ribosomal RNA
      coding region. The DNA plasmid was not transmitted into sexual (ascospore)
      progeny, irrespective of whether the diseased isolate acted as the female or male
      parent. Transmission of the disease to healthy, plasmid-free, "recipient"
      isolates by hyphal anastomosis was not accompanied by transfer of mitochondrial
      DNA or DNA plasmid from the diseased "donor" isolate, but resulted in de-novo
      generation of different plasmids, derived from the recipient's mitochondrial DNA.

PMID- 8299173
TI  - Isolation, characterization and mapping of pyrimidine auxotrophs of Phycomyces
      blakesleeanus.
AB  - A total of seven pyrimidine auxotrophs of Phycomyces were isolated from among 5
      fluoroorotate acid (5-FOA)-resistant mutants. They were classified by
      complementation into two groups. A representative mutant strain belonging to one
      group was deficient in orotate phosphoribosyl transferase (OPRTase; EC 2.4.2.10)
      activity; the mutant strain belonging to the second group was deficient in
      orotidine-5'-monophosphate decarboxylase (OMPdecase; EC 4.1.1.23). These mutants
      are defective in the genes pyrF and pyrG respectively. The results from random
      spore analysis, tetrad analysis, and gene-centromere distances showed that these
      two markers are located in linkage group VI, with pyrG being a proximal marker
      and pyrF a distal one.

PMID- 8299174
TI  - Co-transformation with autonomously-replicating helper plasmids facilitates gene
      cloning from an Aspergillus nidulans gene library.
AB  - Autonomously-replicating, marker-less "helper" plasmids were added to
      transformations of Aspergillus nidulans with plasmids which normally transform by
      chromosomal integration. This resulted in as much as a 200-fold increase in
      transformation efficiency. Recovery of autonomously-replicating plasmid co
      integrates indicated that co-transformation involves recombination between
      integrating and helper plasmids, which occurs at a high frequency. Increasing DNA
      sequence-homology between pairs of plasmids used in simultaneous transformations
      enhanced co-transformation efficiency. Using helper plasmids and an A. nidulans
      gene library in a normally-integrating vector, the genes adC and adD were cloned
      as part of such a co-integrate. In effect, the addition of helper plasmid
      converts an integrating into an autonomously-replicating gene library in vivo.

PMID- 8299175
TI  - Cloning and characterization of the abfB gene coding for the major alpha-L
      arabinofuranosidase (ABF B) of Aspergillus niger.
AB  - Based on amino-acid sequence data from Aspergillus niger alpha-L
      arabinofuranosidase B (ABF B), and cyanogen bromide fragments derived thereof,
      deoxyoligonucleotide mixtures were designed to be employed as primers in a
      polymerase chain reaction (PCR) on A. niger genomic DNA. This resulted in
      amplification of three related PCR products. The abfB gene encoding ABF B was
      isolated from a genomic library using such an amplification product as a probe. A
      5.1-kb BamHI fragment was subcloned to result in plasmid pIM991. Upon
      introduction by co-transformation into both A. niger and A. nidulans uridine
      auxotrophic strains, pIM991 was shown to contain the functional gene since
      prototrophic transformants overproduced ABF B upon growth on the inducing carbon
      source sugar beet pulp. A plate assay was developed enabling quick selection of
      ABF B-overproducing transformants. The sequence of a 4122-bp long BamHI/SstI
      fragment was determined. The abfB gene does not contain introns and codes for a
      protein of 499 amino acids. The mature ABF B, 481 amino acids in length, has a
      deduced molecular weight of 50.7 kDa. A. niger abfB is the first eukaryotic gene
      encoding an ABF to be characterized.

PMID- 8299176
TI  - Transfer of paternal mitochondrial DNA during fertilization of honeybee (Apis
      mellifera L.) eggs.
AB  - Strict maternal inheritance of mitochondrial (mt) DNA is believed to be the rule
      in most eukaryotic organisms because of exclusion of paternal mitochondria from
      the egg cytoplasm during fertilization. In honeybees, polyspermic fertilization
      occurs, and many spermatozoa, including their mitochondria-rich flagellum, can
      completely penetrate the egg, thus allowing for a possibly high paternal leakage.
      In order to identify paternal mtDNA in honeybee eggs, restriction fragment length
      polymorphisms (RFLP) of different subspecies were used. Total DNA extracts of
      different developmental stages of an Apis mellifera carnica x Apis mellifera
      capensis hybrid brood were tested with a radioactively-labelled diagnostic mtDNA
      probe. Densitograms of autoradiographs indicated that the male contribution
      represents up to 27% of the total mitochondrial DNA in the fertilized eggs 12 h
      after oviposition. In subsequent developmental stages the portion of paternal
      mtDNA slowly decreased until hatching of the larvae when only traces were found.
      Although rapid disintegration of paternal mtDNA does not occur, the initially
      high paternal mitochondrial contribution is not maintained in the adult animal.

PMID- 8299177
TI  - Isolation and structure of an acetolactate synthase gene from Schizosaccharomyces
      pombe and complementation of the ilv2 mutation in Saccharomyces cerevisiae.
AB  - A gene encoding a functional acetolactate synthase (ALS) subunit has been
      isolated from the fission yeast Schizosaccharomyces pombe, and has been
      structurally and genetically characterized. The approximate 5-kbp cloned DNA
      segment was found to contain a 2007-bp open reading frame capable of encoding a
      669 aminoacid polypeptide which exhibited 57.1% similarity to the corresponding
      ALS subunit from Saccharomyces cerevisiae. The putative ilv1 isolated from S.
      pombe was shown to encode a functional subunit of acetolactate synthase by
      complementation of an S. cerevisiae strain deleted for the ILV2 locus.

PMID- 8299179
TI  - [The gas hypertension technique in enucleation for ocular melanoma].
AB  - Using the hypertensive gas technique, before touching the melanoma eye for
      enucleation intraocular pressure is raised to maximum by an intravitreal gas
      injection (average 1.2 ml of perfluorocarbon or air), resulting in a rock-hard
      eye. Changes in intraocular pressure are no longer possible, since the hard eye
      condition and avascularity persist during enucleation. The vortex veins appear
      collapsed. Before cutting the optic nerve and vessels, they are compressed by a
      broad hemostatic clamp for three minutes and then severed by a blade located in
      the middle of the clamp. With the hypertensive gas technique there is neither
      bleeding of vortex veins nor of proximal end of stump, which continues to be
      compressed by the hemostatic clamp. Fifteen patients with choroidal melanomas
      were enrolled in a prospective study with the hypertensive gas technique from
      9/1987 to 6/1989; prior radiotherapy was not performed. Average base diameter of
      melanoma measured 13.2 mm, height 8.4 mm. Cytology was: 11x spindle, 3x mixed, 1x
      epitheloid cells. At reexamination in 7/1991 (average follow-up 2.75 years), 2
      diabetics had died with no detectable metastases, and 1 of the 15 melanoma
      patients (6.7%) had died with metastases 2 years after enucleation. The
      hypertensive gas technique does not postpone enucleation of a melanoma eye while
      presumed prophylaxis is administered, does not require additional instruments,
      and takes only a minute when the eye is already draped for surgery. The firm and
      avascular globe facilities a faster removal of the melanoma eye with practically
      no bleeding from the bulb.

PMID- 8299178
TI  - Electrophoretic analysis of the nuclear and organellar genomes in the ultra-small
      alga Cyanidioschyzon merolae.
AB  - Electrophoretic analysis reveals that the nucleus of the ultra-small eukaryotic
      alga Cyanidioschyzon merolae contains approximately 11.7 x 10(6) base pairs (11.7
      Mb) of DNA. This compact genome is fragmented into 15 small chromosomes ranging
      in size from 410 to 1700 kb. The migratory behaviour of chloroplast DNA is
      consistent with the presence of a circular plastid genome of about 170 kb. The
      conformation of mitochondrial DNA resembles that in yeasts and fungi and is
      predominantly linear and heterogenous in size.

PMID- 8299180
TI  - [Surgical treatment of subretinal neovascular membranes. Initial experience].
AB  - Since june 1992 to march 1993 we removed the subretinal neovascular membranes in
      4 patients. In three of them, aged 72-75 years, the membrane was diagnosed by age
      related macular degeneration. In 57-y. old woman the membrane originated
      presumable in an ethiologically uncleared choroiditis. In the last two patients
      we used technique after Thomas and Kaplan with special instruments from DORC. In
      one patients the visual acuity improved and in three patients remained same, or a
      little worse than before. The chirurgical removal of the subretinal neovascular
      membrane is an alternative mode in the treatment of these membranes.

PMID- 8299181
TI  - [Bilateral retinal detachment].
AB  - In 1977-1990 a total of 2,554 patients with rhegmatogenic retinal detachment were
      operated by the cryosurgical method, using silicone episcleral implants. The
      total number of patients comprosed 36 (1.4%) where the authors detected during
      the preoperative examination retinal detachment, usually in an initial stage, on
      the other eye. In 30 patients the authors operated bilateral detachment of the
      retina simultaneously and in the remaining six during the same hospitalization.
      The poorer eye was characterized by 1. more extensive retinal detachment, 2. a
      higher grade of proliferative vitreoretiopathy (PVR). As to the preoperative
      findings, the authors consider the following points important: 1. Almost 70% of
      the patients did not report subjective complaints of the better eye. 2. With
      regard o the pathogenesis the patients were divided into three groups: lattice
      degenerations in 61.1%, idiopathic oral dialysis 11.1%, other factors 27.8% of
      the patients. 3. Symmetry of the retinal defect up to 90 in two-thirds of the
      patients. 4. Type of operation. On the poorer eye the authors performed segmental
      plombage in 12 eyes (33.3%), cerclage in 5 eyes (139%) and reinforced cerclage in
      19 eyes (52.8%). For the better eye the authors indicated segmental plombage in
      12 eyes (77.8%), cerclage in 4 eyes (11.1%) and reinforced cerclage in 4 eyes
      (11.1%). Subretinal fluid was punctured on the poorer eye in 19 eyes (52.7%) and
      on the better eye in 7 eyes (19.4%). After an average observation period of 40
      months the retina became anatomically attached in 86.0% on the poorer eye, and in
      100% on the better eye. Bilateral retinal detachment in our group can be
      considered a model situation of retinal detachment which developed roughly at the
      same time and under equal endogenous conditions of the given organism. It may be
      thus assumed that a different extent of detachment and grade or proliferative
      vitreoretinopathy before operation was determined above all by the period of
      retinal detachment.

PMID- 8299182
TI  - [Development of cataract surgery and implantation of artificial intraocular
      lenses in Czecho-Slovakia 1988-1992].
AB  - After a brief introduction on the history of implantations of synthetic
      intraocular lenses in Czechoslovakia the authors present an analysis of surgery
      of cataract and implantation of artificial intraocular lenses during the past
      five years in Czechoslovakia. The number of operations of cataract increases
      every year, a substantial increase was recorded in particular in 1992. During the
      other years there is also a change from intracapsular to extracapsular extraction
      of cataract and a slow onset of phacoemulsification. The number of departments
      where artificial lenses are implanted is increasing as well as the ratio of
      implantations in relation to the total of cataract surgery. In particular during
      the remaining three years a marked rise of implantation of posterior chamber
      lenses was recorded and a decline in implantations of iris-clip lenses. Almost
      95% of implantations of posterior chamber lenses is considered satisfactory,
      while less than 60% implantations from the total number of cataract surgery is
      still insufficient.

PMID- 8299183
TI  - [The myopic intraocular lens in a phakic eye. Initial experience].
AB  - The very first experiences with implantation of 3 phakic anterior chamber lenses
      for high myopia correction are presented. After average 4 month follow up good
      stability and transparation of concave lenses type ZB5M were observed with
      accurately achieved correction postoperatively.

PMID- 8299184
TI  - [Isolated leukemic infiltration of the iris].
AB  - A boy 3 1/2 years old with the diagnosis acute lymphoblastic leukemia, in stage
      of high malignity, came to the Eye clinic in Hradec Kralove. The clinical and
      haematological findings showed the remission of the illness but a leukemic
      infiltration with hypopyon had arised. The diagnosis has been done selon the
      clinic image of the eye and selon the ultrasound examination. The histologic
      finding showed also an infiltration of chorioidea, iris and ciliary body, an
      infiltration in the nuchal region, in the spleen and in testicles. The isolated
      leukemic infiltration of the iris can be the first sign of a relapse and is an
      indication to begin a relevant therapy.

PMID- 8299185
TI  - [Lymphocytic infiltration in uveal melanoma].
AB  - After our observation of lymphocytic infiltration in uveal melanomas we present
      theoretical review to this interesting topic. Due to relatively low incidence of
      this feature we haven't got sufficiently large collection of cases for
      presentation of our statistically significant conclusions.

PMID- 8299186
TI  - [AIDS and the eye].
AB  - We are observing a patient who is HIV positive since 1987 and in 1992 he got sick
      of AIDS. The first ophthalmologist symptom of the illness was a blurred disc
      margin of the optic nervehead with minor peripapillary hemorrhages and reduction
      of his visual acuity. After two months the condition of the fundus has improved
      but on the eyelash in the nasal half a Kaposi sarcoma is emerging. After six
      month of being sick of AIDS we are observing a reduction of visual acuity on the
      left eye and we diagnosed a Cytomegalic viral retinitis which is also confirmed
      serologically. Inspite of the treatment by Gancyclovir his condition is not
      improving and minor hemorrhages as well as microaneurysms are emerging also in
      macular area of the right eye.

PMID- 8299187
TI  - [Mariotte's spot].
AB  - The blind spot with 25 healthy persons (between 19 and 64 years of age) was
      examined by the Octopus instrument, program 62. The established size of the blind
      spot for the right visual field was: 14.6 degrees +/- 0.86 up to 18.6 degrees +/-
      1.5 laterally from the place of fixation and 1.4 degrees +/- 2.2 up to 4.9
      degrees +/- 3.5 under the horizontal line. The depth of the defects -93.6 degrees
      +/- 18.9 dB for the right visual field. The established size for the left visual
      field was 13.2 degrees +/- 1.5 up to 16.1 degrees +/- 2.5 laterally from the
      place fixation and 2 degrees +/- 3 up to 4.9 degrees +/- 3 under horizontal line.
      The depth of defects is for the left visual filed -99.2 +/- 15.5 dB.
      Statistically there was no evident difference of the size and depth of the
      defects of the blind spot (alfa = 0.01) either between the right and the left
      visual field or among the individual age groups. Physicians applying computerized
      static perimetry should know about the spatial characterization of the individual
      examination programs, of the physiological size and of the possible variations of
      the Mariott's Point and they should evaluate the correlation of all the
      quantities.

PMID- 8299188
TI  - [An operating table for ocular microsurgery].

PMID- 8299189
TI  - [Secondary myelodysplastic syndrome in a boy with non-Hodgkin's lymphoma].
AB  - The authors describe the case-history of a boy with secondary myelodysplastic
      syndrome (MDS) which developed into acute leukaemia. The latter was quite
      resistant to treatment. The disease was preceded by treatment of NH lymphoma with
      a high grade of malignity by radiotherapy and chemotherapy. The authors give the
      total doses of all cytostatics which were administered to the patient. One year
      prior to diagnosis of MDS cytogenetic examination of peripheral blood revealed a
      highly pathological karyotype, from the numerical and structural aspect. Among
      others monosomy of chromosome no. 5 was found which is typical for MDS and these
      changes indicate as a rule a poor prognosis and relatively early transformation
      to acute leukaemia.

PMID- 8299190
TI  - [Magnetic resonance imaging of the postoperative status in children with
      congenital heart defects].
AB  - The justification of examinations by magnetic resonance and the results of
      visualization of cardiac and vascular structures in relation to the performed
      surgical operation were evaluated retrospectively in 24 children after surgery of
      congenital heart disease. Thirteen patients had an operation of coarctation or a
      double aortic arch and four had an operation of an anomaly of the branch of the
      pulmonary artery-its loop or atresia. Seven patients had operations, mostly
      complicated inborn heart disease, of the common arterial trunk and transposition
      of the large arteries with a conduit, tricuspidal atresia after Fontan's or
      Glenn's modified operation and ligature of an aortal aneurysm. At the time of
      examination the patients were 4 to 18 years old. Spin echo sequences obtained by
      basic reconstructions of T1 and possibly T2 weighted images on a 1.5 T Magnetom
      apparatus Siemens proved an excellent visualization in the area of the large
      arteries and the capacity of detailed visualization of cardiac structures, incl.
      changes of the vascular wall in relation to the performed operation. Magnetic
      resonance examinations provided accurate information on central anastomoses and
      conduits as well as on changes of the vascular lumen. The investigation confirmed
      that magnetic resonance is suitable for visualization of postoperative changes
      and findings of morphological structures in particular at sites of cardiovascular
      anastomoses where magnetic resonance supplements the visualization capacity of
      echocardiography and substitutes invasive examinations where only an angiographic
      examination is needed. In eight instances the examination was supplemented by
      invasive assessment of haemodynamic conditions.

PMID- 8299191
TI  - [Lactose intolerance in the differential diagnosis of abdominal pain in
      children].
AB  - In the period from 1990 to 1992 542 children aged 0-15 years were examined by the
      breath hydrogen test for abdominal pain and chronic nutritional disorder. The
      results of lactose tests were pathological in 107 children with abdominal pain
      and 95 with chronic nutritional disorder. The authors followed 107 children with
      abdominal pain and directed their attention to its relationship to lactose
      intolerance. It was confirmed to be the only cause of abdominal pain in twenty
      six children (24.3%). In spite of the well known pathogenetic mechanism of
      lactose intolerance leading to abdominal pain and metheorism and loose stools, an
      atypical clinical course was observed in these patients. There were no complaints
      associated with the intake of milk in history, the abdominal pain being the
      leading symptom in all patients but four who had loose stools. There was an
      improvement of clinical symptoms after the low-lactose diet.

PMID- 8299192
TI  - [Abdominal pain in childhood caused by stenosis of the pyelo-ureteral junction].
AB  - The authors describe three patients with episodes of abdominal pain where despite
      a negative finding in the urine sonography revealed dilatation of the hollow
      system. Urography proved stenosis of the pyeloureteral junction. The authors
      discuss the cause of abdominal pain. Consistent with data in the literature, the
      authors draw attention to pitfalls in the diagnosis of hydronephrosis. They
      recommend sonographic examination of children with abdominal pain, as a negative
      urinary finding does not rule out hydronephrosis. In this respect screening of
      hydronephrosis and other obstructive anomalies during the neonatal period is an
      advantage.

PMID- 8299193
TI  - [The significance of Helicobacter pylori infection in the etiology of abdominal
      pain in children].
AB  - Chronic and recurrent abdominal pain are frequent diagnostic problems in school
      age and adolescent children. The authors examined the IgG antibodies to
      Helicobacter pylori using ELISA in a group of 91 children. Positive results were
      found in 20 children, i.e. 22%. All children positive for Helicobacter pylori
      antibodies underwent an endoscopic examination with bioptic sampling of the
      gastric and duodenal mucosa. Bioptic samples were examined histologically and
      Helicobacter pylori was identified microscopically and using urease tests and
      cultivation. All 20 children with antibodies to Helicobacter pylori had
      histological evidence of chronic gastritis in the gastric antrum and infection
      with Helicobacter pylori was found in 16 cases. Detection of Helicobacter pylori
      IgG antibodies is useful in the selection of patients for endoscopic examination
      of the stomach and duodenum. Endoscopy is relevant also where antibodies to
      Helicobacter pylori are negative and the characteristic picture of chronic
      disease of the upper gastrointestinal tract is present.

PMID- 8299194
TI  - [The hemolytic-uremic syndrome in enterocolitis caused by Campylobacter jejuni].
AB  - In the submitted case-history the authors describe the clinical course of
      haemolytic-uraemic syndrome (HUS) during Campylobacter infection in a two-year
      old boy. On the described case the authors wish to confirm that in the
      manifestation of HUS in childhood not only infections caused by the usual
      microbial agents can participate but also Campylobacter jejuni.

PMID- 8299195
TI  - [Prevention of type I diabetes mellitus in children and risks in infant
      nutrition].

PMID- 8299196
TI  - [Metabolism of calcium and phosphorus in childhood].

PMID- 8299197
TI  - [Orthopedic surgery in children with cerebral palsy].
AB  - The authors present their experience with orthopaedic surgical treatment of
      children with cerebral palsy. The paper is based on a group of 630 patients where
      they performed 1882 operations of the lower extremities in 1970-1992. The authors
      evaluate the long-term results in regularly checked 361 patients (205 boys and
      156 girls), mostly with the spastic form of cerebral palsy, with regard to
      different types of affections which markedly influence the prognosis of surgery
      (monoparesis, hemiparesis, diparesis, triparesis, quadruparesis). The authors
      emphasize the primary importance of rehabilitation and team work where the
      orthopaedist's work is guided by efforts to make further rehabilitation training
      possible and to facilitate it. They consider surgery an integral part of
      comprehensive treatment of cerebral palsy which must be followed immediately by
      further rehabilitation. The authors emphasize the part played be the orthopaedic
      surgeon to prevent the genesis and development of deformities of the locomotor
      apparatus.

PMID- 8299198
TI  - [Polymicrobial infections in recurrent tonsillitis and adenoiditis in children].
AB  - Bacteriological examination focused on the aerobic and anaerobic flora from
      ectomized tonsils in 17 patients with recurrent tonsillitis, in 8 patients with
      hypertrophy of the tonsils and 122 children with an adenoid vegetation confirmed
      microbial aetiology. In ectomized tonsils and adenoids aerobic gram-positive
      bacteria comprised most frequently staphylococci, and gram-negative bacteria H.
      influenzae. As to anaerobic gram-positive bacteria, they isolated most frequently
      peptostreptococci, and as to gram-negative ones B. fragilis from tonsils and
      Bacteroides sp. from adenoids. In the treatment of recurrent infections of the
      upper respiratory pathways it is important to use preferentially aminopenicillins
      combined with beta-lactamase inhibitors and lincosamides.

PMID- 8299199
TI  - [The pediatric part of the National Cholesterol Education Program--one of the
      important aspects of modern nutrition of children and adolescents].

PMID- 8299200
TI  - [Thorax--an atlas of radiographic images of childhood lung diseases].
AB  - At the Paediatric Clinic of the Institute for Postgraduate Medical Training in
      the University Thomayer Hospital in Prague an extensive archive of rare X-ray
      findings from the field of child pneumology was assembled which is used for
      postgraduate medical training. To facilitate physical manipulation of the
      documents the X-ray pictures were transferred to a computer data base. For
      storage the Thorax programme was used which is distributed on CD-ROM. The authors
      discuss the use of this programme in practice. At present the data base comprises
      529 digitalized X-ray pictures of 149 case-histories of pulmonary diseases of
      child patients.

PMID- 8299201
TI  - [Use of fabric and paper diapers in infants and toddlers and their relation to
      hip dysplasia and so-called diaper dermatitis].

PMID- 8299202
TI  - Ultrasensitive immunoassay techniques.
AB  - Ultrasensitive detection of clinically important substances using assays based on
      ligand:binder interactions has revolutionized laboratory medicine. Various
      strategies have been perfected to push the analytical sensitivity of
      ligand:binder assays (e.g., immunoassay, blotting, nucleic acid hybridization
      assay) into the attomole and zeptomole region (10(-18)-10(-21) mol). These
      include the use of labels with amplifying properties (e.g., enzymes), multiple
      labeling, and cascade reactions. In addition a wide range of ultrasensitive
      luminescent detection reactions have been developed for conventional enzyme
      labels based on chemiluminescent, bioluminescent, and time-resolved fluorescent
      reactions.

PMID- 8299203
TI  - G protein mutations in human disease.
AB  - The heterotrimeric G proteins couple cell-surface receptors for extracellular
      signals to intracellular effectors that generate second messengers. Abnormal G
      protein signalling, resulting from posttranslational modifications by bacterial
      toxins, altered gene expression, or gene mutations, may lead to diverse
      biological consequences. Mutations within G protein alpha subunit genes that lead
      to either constitutive activation or loss of function have been identified. Such
      G protein mutations play a role in the pathogenesis of several human diseases,
      including sporadic endocrine tumors, McCune-Albright syndrome, and Albright
      hereditary osteodystrophy.

PMID- 8299204
TI  - Biochemistry of Alzheimer's disease amyloid plaques.
AB  - One of the principal identifying features of Alzheimer's disease (AD) is the
      extracellular deposition of fibrous protein aggregates in the form of amyloid
      plaques. The major component of these deposits is the amyloid beta (A beta)
      protein that is a proteolytic fragment of the integral membrane amyloid precursor
      protein (APP). Understanding the pathways responsible for A beta formation and
      the mechanism by which it accumulates within the brain could provide key answers
      to AD pathogenesis. This review will explore the biochemistry of A beta and its
      precursor, the possible causal relationship between amyloid and AD-associated
      neuronal death, the role of additional cellular elements in amyloid formation,
      and the potential application of these components in clinical diagnosis.

PMID- 8299205
TI  - Human disease, free radicals, and the oxidant/antioxidant balance.
AB  - The reduction of molecular oxygen by healthy cells is a finely tuned, tightly
      controlled process. When cells are sick or injured they make increased amounts of
      superoxide radical (O2.-) and hydrogen peroxide. A few recurring basic mechanisms
      appear to be responsible for the free radical-mediated components of a broad
      spectrum of disease states. Recent research indicates that the relationship
      between superoxide radical and the enzymes responsible for its removal (the
      superoxide dismutases, SOD) reflects a much more delicate balance than was first
      envisioned. When used therapeutically at high doses, SOD either loses its ability
      to protect ischemically injured isolated hearts, or actually exacerbates the
      injury. This concept of a "downside" due to too much superoxide dismutase is
      strongly supported by other studies in which SOD is genetically overexpressed,
      causing a variety of metabolic problems.

PMID- 8299206
TI  - Reperfusion injury after myocardial infarction: the role of free radicals and the
      inflammatory response.
AB  - Development of thrombolytic therapy as a treatment for myocardial infarction has
      focused attention on the events that occur upon reperfusion of ischemic
      myocardial tissue. Although it is well documented that salvage of the ischemic
      myocardium is dependent upon timely reperfusion, it is likely that the very
      events critical for survival may, in fact, lead to further tissue injury. A
      widely recognized source of reperfusion injury is the generation of oxygen
      derived free radicals. These reactive oxygen species, which are formed within the
      first moments of reperfusion, are known to be cytotoxic to surrounding cells. In
      addition, strong support exists for the involvement of the inflammatory system in
      mediating tissue damage upon reperfusion. Coincident with the recruitment of
      neutrophils and activation of the complement system is an increase in the loss of
      viable cells. Although a number of mechanisms are likely to be involved in
      reperfusion injury, this discussion focuses on the roles that oxygen-derived free
      radicals and the inflammatory system play in mediating reperfusion injury.

PMID- 8299207
TI  - Perspectives on lead toxicity.
AB  - Lead toxicity causes hematological, gastrointestinal, and neurological
      dysfunction in adults and children. Symptoms are usually noted with blood lead
      greater than 1.93 mumol/L. Severe or prolonged exposure may also cause chronic
      nephropathy, hypertension, and reproductive impairment. Lead inhibits enzymes;
      alters cellular calcium metabolism; stimulates synthesis of binding proteins in
      kidney, brain, and bone; and slows nerve conduction. Less severe exposure to
      lead, designated by blood lead levels of 0.48-0.96 mumol/L, has been implicated
      in poor pregnancy outcome, impaired neurobehavioral development, reduced stature
      in young children, and higher blood pressure in adults. Biochemical and systemic
      effects of high and low level lead toxicity are described. Dust, water, and paint
      chips are still major sources of lead but lead from folk remedies, cosmetics,
      food supplements, food preparation utensils, and improperly prepared infant
      formula has caused epidemic and sporadic severe lead toxicity. Screening for
      pediatric low level lead exposure requires measurement of blood lead.

PMID- 8299208
TI  - Purification and characterization of human meningioma M2-type pyruvate kinase.
AB  - The M2-type pyruvate kinase was purified from human meningioma by ammonium
      sulfate precipitation, followed by ion exchange and affinity chromatography. The
      specific activity of the purified enzyme was 33.4 U/mg with a yield of 6.5%. The
      enzyme gave a single band with 63,000 +/- 2000 Da upon SDS polyacrylamide gel
      electrophoresis. On cellulose acetate electrophoresis zymograms, the purified
      enzyme (M2) showed a single band, while crude extracts gave two broad bands
      corresponding to pyruvate kinase isozymes. The pI value of purified enzyme was
      found to be 6.9. With phosphoenol pyruvate as substrate the purified enzyme
      showed sigmoidal kinetics, while in the presence of 0.6 mM fructose 1,6
      diphosphate as modulator it gave a hyperbolic saturation curve with a Km value of
      0.53 mM.

PMID- 8299209
TI  - High voltage electrophoresis of amino acids in urine containing ampicillin.
AB  - Analysis of amino acids is complicated by treatment with ampicillin. High voltage
      electrophoresis, which is convenient for the qualitative assessment of metabolic
      diseases, yields smears of ampicillin that mask the bands of citrulline,
      homocitrulline, phenylalanine, cystine, and homocystine. The addition of
      penicillinase prior to high voltage electrophoresis eliminates ampicillin and
      other penicillins and reveals these key amino acids.

PMID- 8299210
TI  - Interindividual variation in the partition of lipoprotein(a) into lipoprotein
      subfractions.
AB  - In order to evaluate cardiovascular risk, we analyzed the lipid composition of
      HDL and the presence of lipoprotein(a) [Lp(a)] by both agarose gel
      electrophoresis and enzyme-linked immunoassay (ELISA). In 681 plasmas we found a
      close correspondence between the existence of a visible sinking pre-beta
      lipoprotein band and a concentration of Lp(a) higher than 300 mg/L. In the
      sinking pre-beta(+) samples, the HDL-cholesterol level obtained by differential
      ultracentrifugation was significantly higher than that obtained by precipitation
      with the MgCl2-phosphotungstic acid reagent; and the difference between these HDL
      cholesterol values was linearly correlated with plasma Lp(a) concentration.
      Moreover, the other HDL lipid components and the lipid mass ratios of HDL
      isolated by ultracentrifugation were significantly different from those of HDL
      isolated by precipitation, and these changes were also correlated with plasma
      Lp(a). These differences are attributed to Lp(a) because it was detected in the
      1.063-1.21 kg/L plasma fractions, whereas it was absent in the plasma supernates
      after precipitation with MgCl2-phosphotungstic acid. Although to a lesser extent,
      Lp(a) was also present in the LDL and VLDL density ranges and it directly
      depended on both the Lp(a) and the triglyceride plasma concentrations. The
      proportion of Lp(a) in HDL as related to that in LDL density fractions decreased
      as Lp(a) plasma levels increased, reflecting an interindividual variation of
      Lp(a) density species. Since 90% of our study population had detectable Lp(a) in
      plasma, the results reinforce the concept that the ultracentrifugation method is
      not equivalent to precipitation in most samples, and the contaminant effect of
      Lp(a) cannot be predicted because of Lp(a) partition into the different
      lipoprotein fractions.

PMID- 8299211
TI  - Significance of various parameters derived from biological variability for lipid
      and lipoprotein analyses.
AB  - Analytical, within-subject, and between-subject components of variability have
      been determined for total cholesterol, LDL-cholesterol, HDL-cholesterol, and its
      HDL2 and HDL3 subfractions, triglycerides, apolipoproteins A-I and B, and
      lipoprotein(a) in serum specimens from a cohort of 10 healthy subjects over a 1
      month period. From these data, we have calculated the desirable analytical
      imprecisions, the indices of individuality, the critical differences for
      significant change detection, and the number of specimens required to estimate
      the homeostatic set-point of an individual. Practically, the analytical goal for
      imprecision was not achieved for HDL2 subfraction, lipoprotein(a), and direct LDL
      cholesterol determination (obtained vs. theoretical analytical CV, 8.2% vs. 5.9%,
      7.4% vs. 3.8%, and 3.2% vs. 2.6%, respectively). All analytes had marked
      individuality, showing that the use of population-based reference values is
      inadequate for their interpretation. The applicable differences required for two
      results to be significantly different (p < or = 0.05) are total cholesterol: 10%;
      triglycerides: 49%; LDL-cholesterol: 16%; HDL-cholesterol: 14%; HDL2-cholesterol:
      40%; HDL3-cholesterol: 16%; apolipoprotein A-I: 11%; apolipoprotein B: 12%; and
      lipoprotein(a): 29%. Furthermore, it should be clear that population screening
      for the assessment of risk of coronary artery disease by means of some of the
      assays studied would result in a significant number of patients requiring
      analysis of multiple specimens.

PMID- 8299212
TI  - A case of benign familial hyperphosphatasemia of intestinal origin.
AB  - We recently encountered a case of hyperphosphatasemia, in which > 90% of serum
      alkaline phosphatase (ALP) was of intestinal origin. The patient, a 51-year-old
      man, was found to have hyperphosphatasemia (2,341 U/L) during a routine medical
      check-up. All other laboratory tests and physical findings were normal. The
      agarose gel electrophoresis pattern of the patient's serum ALP was identical to
      that of common intestinal ALP from healthy adults, and only a single band of
      intestinal ALP was detected by immunoaffinity electrophoresis. In addition, 89%
      of total ALP was defined as intestinal ALP by an immunoprecipitation method. The
      molecular mass of the ALP was 154 kDa, almost identical with that of adult
      duodenal ALP. Analysis of the sugar chain structure showed an increased la
      fraction (74%) compared with adult duodenal ALP. Genealogical study revealed that
      two persons in the 5 members of the proband's family had hyperphosphatasemia of
      intestinal origin, indicating possible autosomal dominant inheritance.

PMID- 8299213
TI  - Biochemical and immunological characteristics of neutrophil alkaline phosphatase
      in Down's syndrome.

PMID- 8299214
TI  - Vigabatrin--interference with urinary amino acid analysis.

PMID- 8299215
TI  - Oxidative metabolism and severe asthma in children.

PMID- 8299216
TI  - A radioimmunoassay for pancreatic elastase 1: use of alpha 1-antitrypsin-elastase
      1 conjugate as both standard and tracer to eliminate the influence of anti
      elastase 1 autoantibodies.
AB  - We have recently reported the occurrence of anti-elastase 1 autoantibodies in
      human sera (Asada et al., Biochim Biophys Acta, 1991;1080:34-39). The usual
      radioimmunoassay of elastase 1 in autoantibody-positive sera gave abnormally high
      levels of elastase 1 and low recoveries of elastase 1 added to the sera. Now we
      have established a new radioimmunoassay system for determining pancreatic
      elastase 1 in serum, in which alpha 1-antitrypsin elastase 1 conjugate, the major
      conjugation form of elastase 1 in serum, is used as standard and alpha 1
      antitrypsin-[125I]elastase 1 as tracer, because we found that the conjugate could
      bind to the elastase 1 specific antiserum but not to the autoantibodies. Thus the
      new assay system completely eliminate the unfavorable effects of the
      autoantibodies. The elastase 1 levels determined by the new assay method
      exhibited a good correlation with those obtained by a commercial assay kit in the
      autoantibody-negative sera, while no correlation was observed in the autoantibody
      positive sera.

PMID- 8299217
TI  - Repertoires of natural autoantibodies against muscle tissue are independent of
      age or gender in normal human adults. A western blot study.
AB  - Sera from 69 healthy blood donors were screened for autoantibodies using Western
      blots of human muscle fractions to assess whether prevalence and repertoires of
      autoantibodies against muscle tissue would change with age. Each serum contained
      immunoglobulins binding to a broad spectrum of antigens. Their molecular masses
      ranged from 20 to more than 200 kDa. Although each staining pattern appeared to
      be a singular combination of detected bands and staining intensities, the
      patterns were not different in men and women. When sera were grouped according to
      age (decades between 10 and over 70 years) age-dependent changes were not found.
      Individual repertoires of natural autoantibodies against muscle tissue are
      complex when examined by Western blotting. Mature normal repertoires of low
      affinity autoantibodies are found at the age of 10 years which is the lower cut
      off in this study. The repertoires remain stable throughout a normal lifespan.

PMID- 8299218
TI  - Malondialdehyde adducts to, and fragmentation of, apolipoprotein B from human
      plasma.
AB  - Many recent in vitro experiments support the hypothesis that oxidatively modified
      low density lipoproteins (LDLs) could participate in atherogenesis. Oxidation of
      LDLs, especially derivatization by aldehydes originating from peroxidation of
      fatty acids and fragmentation of apolipoprotein (apo) B-100 which is their major
      apolipoprotein, probably occurs extravascularly and the presence of oxidized LDLs
      in the circulation is not well documented. Using electrophoresis and
      immunodetection techniques, we studied the structure of apo B and the presence of
      adducts of malondialdehyde (MDA) to this protein in LDLs from plasma of a limited
      population of five healthy subjects and nine patients with severe
      atherosclerosis. In the patient-derived LDLs, apo B appeared extensively
      fragmented, much more so than in those from the healthy subjects, although LDLs
      were isolated in all cases in the presence of antioxidants, protease inhibitors
      and antibiotics. Additionally, in all healthy subjects, we found a minor fragment
      of apo B-100, apo B-74, whereas the complementary peptide, apo B-26, was not
      detected; thus the presence of this minor form cannot be related to cleavage of
      apo B-100, either by proteolysis or by oxidation. We also present evidence that
      MDA adducts are present in circulating apo B and most of its fragments not only
      in atheromatous patients, but also in healthy subjects. Our results are
      consistent with the existence of oxidized LDLs in the human circulation. However,
      the role of non-oxidative phenomena in the structural modifications affecting apo
      B which are reported here cannot be excluded.

PMID- 8299219
TI  - Serum tissue inhibitor of metalloproteinases in patients with chronic liver
      disease and with hepatocellular carcinoma.
AB  - To examine the clinical significance of serum level of tissue inhibitor of
      metalloproteinases (TIMP) in chronic liver disease and in hepatocellular
      carcinoma, we measured serum TIMP concentration by a sandwich enzyme immunoassay
      in 79 patients with chronic liver disease and 49 patients with hepatocellular
      carcinoma. Serum TIMP concentration was 164 +/- 20 ng/ml in healthy controls, and
      was 10% higher than control in chronic persistent hepatitis, 36% higher in
      chronic active hepatitis, 62% higher in liver cirrhosis and 30% higher in primary
      biliary cirrhosis. Serum TIMP level was closely correlated with serum level of
      type IV collagen 75 domain and with the histological degree of liver fibrosis in
      chronic liver disease. Serum TIMP level in hepatocellular carcinoma was increased
      2.3-fold compared with that in controls, and was significantly higher than in
      liver cirrhosis. Serum TIMP level increased with tumor size, and significantly
      correlated with serum alpha-fetoprotein level. Gel filtration on Sephadex G-75
      showed that the TIMP in serum was present as an enzyme-complexed form. These
      results suggest that the measurement of serum TIMP concentration is useful in the
      clinical assessment of liver fibrosis in chronic liver disease and of the
      development of hepatocellular carcinoma.

PMID- 8299220
TI  - Human seminal deoxyribonuclease I (DNase I): purification, enzymological and
      immunological characterization and origin.
AB  - Deoxyribonuclease I (DNase I) was purified from the semen of a 38-year-old male
      and then characterized. The catalytic properties of the purified enzyme closely
      resembled those of DNase I purified from the urine of this individual and the
      following other similarities were observed: molecular masses, iodoacetic acid
      inactivation kinetics, desialylated isoenzyme patterns. However, the behavior of
      the purified enzymes determined on several different lectin-affinity
      chromatography columns differed, which suggests that organ-specific glycosylation
      of DNase I occurs. Multiple forms of the purified seminal DNase I were
      demonstrated, each of which had a different pI value separated by isoelectric
      focusing, which is compatible with the reported existence of genetic polymorphism
      of seminal DNase I (Sawazaki et al., Forensic Sci Int 1992;57:39-44).
      Furthermore, enzymological and immunological comparisons of purified seminal and
      urinary and partially purified prostatic DNases I indicated that the prostate may
      be one of seminal enzyme source tissues.

PMID- 8299221
TI  - A rate turbidimetric immunoassay for theophylline using biotin-avidin system.
AB  - We describe a biotin-avidin based rate turbidimetric homogeneous immunoassay for
      the determination of serum theophylline with a measuring range of 0-40
      micrograms/ml. The assay features an avidin-biotin-labeled theophylline conjugate
      and a monoclonal antibody. The rate of change of turbidity caused by the antibody
      conjugate complexing was monitored on the Beckman Synchron CX 4 System at 340 nm
      and 37 degrees C. Theophylline in a sample inhibited the complexation, and the
      extent of inhibition allowed the quantitation of theophylline in the sample. The
      within-run coefficient of variation (CV) was < 3.7% and the between-run CV was
      5.2-9.2% depending on the theophylline concentration. Linear regression analysis
      showed a good correlation with an established fluorescence polarization
      immunoassay (r = 0.9866, n = 94).

PMID- 8299222
TI  - 5,6-Dihydrouridine: a marker ribonucleoside for determining whole body
      degradation rates of transfer RNA in man and rats.
AB  - It has previously been demonstrated that N6-threoninocarbonyladenosine is
      virtually quantitatively excreted in urine. From the similarity of the average
      molar ratio of 5,6-dihydrouridine to N6-threoninocarbonyladenosine in the urine
      of human adults (12.6), newborns (12.6) and rats (13.6) with the respective ratio
      in cytoplasmic tRNA (11.8) we conclude that 5,6-dihydrouridine is also virtually
      quantitatively excreted in urine. Therefore, excreted 5,6-dihydrouridine is
      suitable as a marker to assess the whole body degradation rate of tRNA. Relative
      degradation rates of tRNA determined via excreted 5,6-dihydrouridine in urine are
      4.7 times higher in rats (2.2 +/- 0.33 mumol/kg per day) than in human adults
      (0.48 +/- 0.05 mumol/kg per day) which is similar to the respective difference in
      the resting metabolic rate per weight unit.

PMID- 8299223
TI  - Comparison of lipoprotein(a) assay methods in serum and in a plasminogen-free
      fraction.
AB  - We compared five immunoassays for lipoprotein(a) (Lp(a)) determination (end-point
      immunonephelometry, two-site IRMA and three different ELISA methods) in order to
      verify their agreement. Since it has been demonstrated that human apo(a)
      structure is closely similar to that of plasminogen, cross-reactivity of apo(a)
      antibodies with plasminogen represents an important technical problem in serum
      Lp(a) quantification. On this account we used a plasminogen-free fraction
      obtained by one-step ultracentrifugation at a density of 1.125 g/ml, in which no
      plasminogen activity was found. A satisfactory correlation between serum and
      plasminogen-free fraction Lp(a) values was found for all the methods; the limits
      of agreement were too high, however, to use serum and fraction interchangeably.
      Furthermore, it emerged that the different assays were more comparable and
      individual Lp(a) differences between methods were less spread when plasminogen
      free fraction was used instead of serum.

PMID- 8299224
TI  - Quantitation of plasma oxidatively modified low density lipoprotein by sandwich
      enzyme linked immunosorbent assay.

PMID- 8299225
TI  - Relationship between immune complex binding and release and the quantitative
      expression of the complement receptor, type 1 (CR1, CD35) on human erythrocytes.
AB  - Primate erythrocytes (E) play a central role in clearing potentially pathogenic
      immune complexes (IC) from the circulation. E capture circulating IC via
      interaction between C3b and C4b sites, generated on the IC during activation of
      the complement cascade, and the complement receptor, type 1 (CR1), expressed on
      E. IC are released from E when C3b and C4b sites on the IC are cleaved by Factor
      I. The goal of this study was to examine the interactions between human E and
      model IC in the context of quantitative variations in CR1 expression. IC were
      prepared by combining murine monoclonal IgG1, IgG2b, or IgG3 anti-dinitrophenyl
      (DNP) antibodies with DNP-bovine serum albumin. The expression of CR1 on E,
      obtained from eight healthy donors, was quantified by radioimmunoassay and
      Scatchard analysis. On the basis of quantitative CR1 expression, preparations of
      E obtained from different donors at various times were categorized into
      phenotypic groups expressing high, intermediate, or low numbers of CR1. While
      there was some variation in the expression of CR1 of individual donors, five of
      the eight donors remained within the same phenotypic group upon repeated
      sampling. Surprisingly, when interactions between IC and E were examined in
      vitro, there was no direct relationship between the number of CR1 per E and the
      peak magnitude of IC binding to E. When peak binding and release rates were
      calculated, there was a direct correlation between the number of CR1 per E and
      the peak binding rate of IC constructed with IgG3 antibodies (IgG3 IC). In
      addition, there was an inverse correlation between the number of CR1 per E and
      the peak release rate of IgG2b IC. There was no direct correlation between the
      quantitative expression of CR1 on E and the peak binding or release rates of IgG1
      IC. These data indicate that the quantitative expression of CR1 can affect the
      interactions between IC and E, but that these interactions are also dependent
      upon the immunochemical properties of the IC. These findings may be relevant to
      the pathogenesis of diseases, including systemic lupus erythematosus and AIDS, in
      which E express reduced numbers of CR1.

PMID- 8299226
TI  - Autoantibodies to vascular heparan sulfate proteoglycan in systemic lupus
      erythematosus react with endothelial cells and inhibit the formation of thrombin
      antithrombin III complexes.
AB  - Vascular heparan sulfate proteoglycan (vHSPG) is an important functional
      component of the microvasculature. Previous studies have demonstrated
      autoimmunity to vHSPG in systemic lupus erythematosus (SLE). In the current
      studies, we further investigated the immunospecificity of anti-vHSPG antibodies
      in SLE sera by enzyme-linked immunoassay (ELISA). In direct binding assays, SLE
      sera contained IgG antibodies reactive with native vHSPG and with heparan sulfate
      (HS) glycosaminoglycan in significantly higher titers than controls. Employing
      purified SLE IgG in liquid-phase competitive immunoinhibition ELISAs, SLE IgG
      anti-HS antibodies cross-reacted with heparin and DNA, but not with other
      glycosaminoglycans or anionic phospholipid antigens. Immunochemical studies
      demonstrated that the immunodominant site on HS recognized by SLE IgG contained 2
      O-sulfated uronic acid. Removal of N-sulfated and 6-O-sulfated residues primarily
      on N-acetyl-glucosamine had no effect on antigenicity, further demonstrating that
      nonspecific charge interactions which are the result of sulfation do not solely
      account for the antigenicity of HS. SLE IgG from patients with active SLE was
      further affinity purified on DNA-cellulose and HS-Sepharose columns for
      immunospecificity studies. After affinity purification of both anti-DNA and anti
      HS antibodies, significant enhancement of direct binding reactivity with HS was
      noted. In addition, anti-DNA and anti-HS IgG antibody reacted with the cell
      surface of endothelial cells by a cellular ELISA (CELISA). Immunoinhibition
      studies of CELISA reactivity confirmed that affinity-purified SLE IgG anti-DNA
      anti-HS antibody were reactive with endothelial cell surface HS antigens.
      Furthermore, SLE IgG anti-DNA antibody reactivity with endothelial cells was not
      reduced by DNase treatment of the cells, but was significantly reduced by
      heparitinase digestion. Since HS plays an important role in the maintenance of
      normal anticoagulation on the endothelial cell surface by binding antithrombin
      III, we investigated the inhibition of heparin-accelerated thrombin-antithrombin
      III complex formation by SLE IgG. Purified IgG from patients with active SLE, but
      not from normal controls, inhibited heparin-accelerated formation of TAT
      complexes. These studies demonstrate the presence of IgG autoantibodies to HS in
      patients with SLE. Anti-HS antibodies recognize an antigenic site also present in
      heparin, but not other glycosaminoglycans, bind to the endothelial cell surface,
      and inhibit the formation of TAT complexes. SLE IgG anti-HS antibodies recognize
      a sulfated uronic acid epitope containing 2-O-sulfate which is important in
      certain functions of HS, including antithrombin III binding. Thus, anti-HS
      antibodies may promote a procoagulant state at the endothelial cell
      surface.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8299227
TI  - Selectivity of recognition of variable (V) regions of autoantibodies by
      intravenous immunoglobulin (IVIg).
AB  - In the present study, we demonstrate that intravenous immunoglobulin (IVIg) is
      capable of binding to variable (V) regions of anti-endothelial cell antibodies
      (AECA) of healthy donors and patients with systemic lupus erythematosus (SLE).
      Among V regions of AECAs, IVIg selectively recognized certain idiotypes expressed
      by the autoantibodies of a given individual, in the case of both natural and SLE
      associated AECAs. These observations provide new and direct evidence that IVIg
      interacts idiotypically with V regions of autoantibodies and that the efficacy of
      such interaction depends on individual autoantibody specificity. Our findings may
      be relevant for the understanding of the mechanisms that control expression of
      natural autoantibody activity in serum and for that of the differences in
      response to IVIg therapy that are seen between patients with autoimmune disease.

PMID- 8299228
TI  - Ethanol inhibits early events in T-lymphocyte activation.
AB  - Ethanol has been reported to be immunosuppressive. We have studied the effects of
      ethanol on early activation events related to the proliferative response of human
      T lymphocytes. Ethanol inhibited T-cell proliferation in a dose-dependent manner.
      To define the target of this ethanol-mediated inhibition of T-cell function we
      examined its effect on the activation of T lymphocytes or induction of competence
      (acquisition of responsiveness to interleukin (IL)-2 or IL-4) by
      phytohemagglutinin (PHA) or the combination of phorbol dibutyrate
      (PDB)/ionomycin. Ethanol inhibited induction of competence with PHA by up to 50%
      when compared to control cells. In contrast to the effects on PHA-mediated
      activation of the cells, ethanol exerted no inhibitory action on the induction of
      competence by PDB/ionomycin. Ethanol also inhibited the induction of c-fos by PHA
      but not by PDB/ionomycin. To investigate the basis for these differences, the
      effects of ethanol on Ca2+ mobilization were examined. Ethanol inhibited PHA
      induced Ca2+ mobilization in a dose-dependent manner. This inhibition was exerted
      mainly on transmembrane Ca2+ influx rather than on release of Ca2+ from
      intracellular stores. Ethanol did not affect Ca2+ mobilization induced by
      ionomycin. Co-incubation of ionomycin with PHA, during the induction of
      competence, abolished the inhibition exerted by ethanol when compared to cells
      treated with PHA alone. The inability of ethanol to exert complete inhibition on
      cell proliferation may be due to the activation of Ca(2+)-independent pathways by
      PHA, since combined treatment with ethanol and the intracellular Ca2+ chelator,
      BAPTA, did not completely inhibit the proliferative response. The inhibitory
      effects of ethanol on PHA-induced Ca2+ mobilization and subsequent induction of c
      fos indicate that ethanol interferes with Ca(2+)-dependent pathways activated by
      PHA and this may provide the basis for its immunosuppressive action.

PMID- 8299229
TI  - Early activation events induced by the staphylococcal superantigen toxic shock
      syndrome toxin-1 in human peripheral blood monocytes.
AB  - Staphylococcal exotoxins (SE) bind to MHC class II molecules and induce the
      production of IL-1 beta and TNF-alpha in human monocytic cells. Here we show that
      stimulation of peripheral blood monocytes with toxic shock syndrome toxin-1 (TSST
      1) induced rapid increase in tyrosine phosphorylation of cytosolic protein
      substrates, accumulation of inositol phosphates, and de novo tyrosine
      phosphorylation of the PLC-gamma 1 isozyme. Accumulation of inositol phosphates
      was inhibited by preincubation of cells with inhibitors of protein tyrosine
      kinases (PTK). Stimulation of monocytes with TSST-1 furthermore led to activation
      of protein kinase C (PKC). PTK and PKC activation plays a role in the induction
      of monokine gene transcription by SE because inhibitors of PTK and PKC reduced
      TSST-1-stimulated IL-1 beta and TNF-alpha gene expression. We therefore propose a
      model in which the induction of monokine gene transcription by TSST-1 in
      monocytes necessitates activation of tyrosine kinase(s) and of PKC, the latter
      probably by way of PLC-gamma 1.

PMID- 8299230
TI  - Cell-mediated immunity in allopurinol-induced hypersensitivity.
AB  - Allopurinol may induce severe hypersensitivity characterized by hepatitis,
      interstitial nephritis, and skin rash. The mechanisms for this hypersensitivity
      syndrome are incompletely elucidated. Immunologic studies were performed on
      tissue and peripheral blood lymphocytes from a patient with allopurinol
      hypersensitivity. Immunohistochemistry was performed on sections of the liver
      biopsy utilizing monoclonal antibodies for T and B lymphocytes. Peripheral blood
      lymphocyte immunophenotyping by flow cytometry and peripheral blood lymphocyte
      stimulation studies with either allopurinol or oxypurinol measured as tritiated
      thymidine uptake were performed in the hypersensitive patient and compared to a
      group of six patients treated with allopurinol without hypersensitivity and eight
      normal control patients. Additional single- and dual-color immunophenotyping by
      flow cytometry of oxypurinol-stimulated lymphocytes was performed in the
      hypersensitive patient and compared to normal controls. The liver biopsy
      demonstrated predominantly a T lymphocyte infiltrate. The number of peripheral
      blood lymphocytes expressing activation antigens was significantly greater in the
      hypersensitive patient compared to that of both control groups. Lymphocytes from
      the hypersensitive patient were moderately stimulated by allopurinol and markedly
      stimulated by oxypurinol compared to both control groups. Oxypurinol-stimulated
      lymphocytes from the hypersensitive patient demonstrated enhanced expression of
      activation antigens compared to unstimulated lymphocytes from this patient and
      normal controls. These studies suggest that cell-mediated immunity directed
      toward allopurinol and more importantly to its oxypurinol metabolite is involved
      in the pathogenesis of allopurinol-induced hypersensitivity.

PMID- 8299231
TI  - Immune modulation during treatment of systemic sclerosis with plasmapheresis and
      immunosuppressive drugs.
AB  - Immunologic effects of our previously reported treatment protocol were determined
      in eight systemic sclerosis (SSc) patients treated with plasmapheresis,
      cyclophosphamide, and prednisone as tolerated. Prior to treatment total serum IgG
      and circulating lymphocytes including the percentage of B, T, and NK cells were
      normal. Peripheral blood lymphocytes showed evidence of activation by increased
      spontaneous proliferation and expression of CD25 on T cells. In addition, CD4+ T
      cells showed increased expression of both activation (HLA-DR) and maturation
      (CD29) markers. The percentage of CD8+ T cells was low, resulting in a high
      CD4:CD8 T cell ratio. During treatment all patients showed clinical improvement.
      Laboratory testing showed that their NK cells had declined by 81%, B cells
      declined by 96%, and serum IgG declined by 49%; high titer ANA were abrogated.
      Total T cells declined by 52%, and the CD4:CD8 ratio fell to normal, due to an
      almost twofold increase in the percentage of CD8+ T cells. Spontaneous lymphocyte
      proliferation increased further and was accompanied by increased maturation and
      activation of both CD4+ and CD8+ T cells, as well as a reduction of immature CD4+
      T cells. Among CD8+ T cells the percentage of cytotoxic cells increased as shown
      by an increase in the CD11b-, CD38+, and CD29+ phenotypes, a finding confirmed on
      follow-up three-color flow cytometry which showed an increase in activated CD8
      cells bearing the cytotoxic CD28 marker. Three-color cytometry also showed that
      cells with the CD4+CD45RA+CD31+ suppressor inducer phenotype were low and those
      with the CD4+CD45RO+ CD31- helper inducer phenotype were high in treated SSc
      patients. Deficient CD4+CD45RA+CD31+ and CD8+ T cell populations suggest an
      immune regulatory imbalance in SSc which could have led to CD4+ T cell activation
      and autoimmunity. Depletion of B cells, in conjunction with augmentation of
      cytotoxic CD8+ T cells through combined therapy, may have diminished the
      autoimmune response.

PMID- 8299232
TI  - Immunochemical characterization of monoclonal IgG containing mixed cryoglobulins.
AB  - Monoclonal IgG-containing type II cryoglobulins (CG) from 25 patients, most
      affected with autoimmune or inflammatory diseases, were characterized using a
      Western blotting procedure. Rheumatoid factors were measured by ELISA. Out of the
      25 type II CG, 14 contained a single monoclonal IgG and 11 contained several
      distinct monoclonal Ig, as assessed by the electrophoretic mobility and isotypy
      of the narrow bands. Comparison of blots revealed by anti-IgG subclass antibodies
      in the patients' sera and CG showed a clear-cut enrichment of CG in both
      polyclonal and monoclonal IgG1 and IgG3. All monoclonal IgG in the CG belonged to
      the IgG1 or IgG3 subclasses. CG also contained more detectable RF of the IgM
      class than did the corresponding sera. Using conventional methods, the present CG
      either could not be typed or were all (immunoelectrophoresis) or often
      (immunofixation) classified as type III. The results challenge the classical
      classification of CG and show the necessity of the use of sensitive techniques
      for immunochemical characterization of mixed CG.

PMID- 8299233
TI  - Homozygosity for a missense mutation (G20R) associated with neonatal onset
      adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID).
AB  - Mutations at the adenosine deaminase (ADA) locus can result in varying degrees of
      immunodeficiency, including rapidly fulminant severe combined immunodeficiency
      (SCID) as well as a slowly progressive immunodeficiency not diagnosed until later
      in childhood. Genetic heterogeneity is a factor in the clinical heterogeneity. We
      have now identified, by direct sequencing of PCR-amplified genomic DNA, a G to A
      transition at a CpG dinucleotide predicting a glycine to arginine substitution at
      codon 20 (G20R). The mutation, in homozygosity, was associated with neonatal
      onset rapidly fatal SCID. Consistent with homozygosity, the child was derived
      from a small isolated inbred community in Newfoundland. The mutation abolishes a
      site for the restriction enzyme BamHI and can be simply detected by agarose gel
      electrophoresis following amplification of exon 2 from genomic DNA and digestion
      with BamHI. The majority of ADA missense mutations can now be detected by similar
      amplification and enzyme digestion. We demonstrated that the G20R mutation is
      deleterious since introduction of the mutation into a normal ADA minigene
      abolished enzyme activity, as determined by transient expression in monkey kidney
      (Cos) cells. The amino acid substitution occurs in an area of the molecule
      conserved from Escherichia coli to man and that, as shown by crystallographic
      analysis, is involved in the binding of Zn2+ at the catalytic site. Although the
      mutation is in a CpG dinucleotide, known "hotspots" for G to A transitions, it
      was not found in a series of 43 additional ADA- chromosomes. Identification of
      mutations in additional ADA- patients with immunodeficiency of varying severity
      should further define the role that genotype plays in determining the extent of
      immunologic dysfunction.

PMID- 8299234
TI  - Functional domains on HLA-DR molecules: implications for the linkage of HLA-DR
      genes to different autoimmune diseases.

PMID- 8299235
TI  - Hepatitis B virus antigens in peripheral blood mononuclear cells during the
      course of viral infection.
AB  - We studied the expression of surface (HBsAg) and core (HBcAg) proteins of
      hepatitis B virus (HBV) on the surface of peripheral blood mononuclear cells
      (PBMC) from HBV-infected patients. A total of 122 patients with different liver
      viral diseases was analyzed by indirect immunofluorescence with monoclonal
      antibodies. The 35 patients with HBV chronic active hepatitis (CAH) and 38 of 60
      patients with acute hepatitis B (63%) expressed HBsAg on the PBMC. No expression
      was detected on the cells from both normal and HBV-unrelated viral hepatitis
      control groups. Serial follow-up of patients with acute hepatitis B showed that
      HBsAg expression by PBMC tended to be undetectable 4 months after the onset of
      the disease and at the same time the clinical improvement was evident. Cell
      cultures of EBV-transformed B lymphocytes were established from PBMC of HBV
      infected patients; immunoelectron microscopy demonstrated the HBsAg on the
      cellular membrane. One-third of HBV-infected patients who were studied showed the
      expression of HBcAg by PBMC. HBcAg was detected in patients with acute hepatitis
      B at the early stage of infection. The cells of these patients also expressed
      HBsAg in PBMC. In CAH patients, a positive association was observed between the
      expression of HBcAg and the presence of serum HBeAg.

PMID- 8299236
TI  - Glomerular permselectivity to macromolecules in reflux nephropathy:
      microalbuminuria during acute hyperfiltration due to aminoacid infusion.
AB  - Reflux nephropathy is an important cause of chronic renal failure in children.
      After the parenchymal scar, the progression is thought to be mediated by
      glomerular hypertension in remnant nephrons resulting in modifications in
      permselectivity to macromolecules. Proteinuria correlates with a progressive
      course. The glomerular permselectivity to macromolecules in basal conditions and
      after acute hemodynamic stress was investigated in 28 children whose bilateral
      vesico-ureteric reflux (VUR) had been previously surgically corrected (meanly 5.6
      years before) and with normal creatinine clearance (CrCl). Bilateral renal
      scarring (0 to 8 scale for both kidneys) was 4.3 +/- 1.6. Albuminuria (UAE) was
      evaluated in basal conditions and under acute hyperfiltration induced by amino
      acid (Aa) infusion. After isotonic saline at 310 ml/hour/1.73 m2, 6 mg/kg/min of
      Aa were infused for 2 hrs. UAE was significantly higher than controls in basal
      conditions (p < 0.01), and further increased after Aa infusion (p < 0.02).
      Microalbuminuria was detectable in 53.5% of the children in basal conditions and
      in 64.3% after Aa. Also urinary beta 2 microglobulin significantly increased at
      the end of the test (p < 0.001). CrCl significantly increased at the first hour
      (p < 0.05). Children with severe renal parenchymal scarring had greater UAE (p <
      0.01) and beta 2M (p < 0.02) values after provocative test than those with mild
      renal damage. In 8 children GFR and ERPF were measured by means of inulin and p
      hippurate clearance respectively. The variations in UAE during Aa infusion were
      significantly correlated with GFR dynamics (p < 0.05) while they were not
      influenced by ERPF modifications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299237
TI  - Reflux nephropathy in children submitted to unilateral nephrectomy: a
      clinicopathological study.
AB  - The clinical findings and renal histopathology have been reviewed in children
      with gross primary vesicoureteric reflux (VUR) submitted to unilateral
      nephrectomy. Of the 42 children reviewed, sections of the nephrectomy specimens
      were available in 36. In this series, 34 patients were male and eight were
      female. The boys included seven in which hydronephrosis was identified by fetal
      ultrasound. The male patients tended to present earlier and had nephrectomies
      younger than the females. Segmental scarring was frequent in both males and
      females, but evidence of dysplastic renal development was confined to the male
      patients and occurred in the majority (63%). Acquired mechanisms for the
      induction of segmental renal scarring, involving VUR, intrarenal reflux (IRR) and
      urinary infection, shown to be important in older children, clearly operate in
      infancy. However, this study emphasizes that congenital malformation of the
      kidney is a crucial factor in the development of reflux nephropathy (RN) in this
      younger age group, particularly in males. Speculation on the significance of the
      association between renal dysplasia and RN is discussed in relation to
      observations on the embryological development of the male lower urinary tract.

PMID- 8299238
TI  - Treatment of proteinuric patients with a vegetarian soy diet and fish oil.
AB  - Our aim was to determine whether a longer period of treatment with a vegetarian
      soy diet with addition of fish oil supplements would accentuate the beneficial
      effects on hyperlipidemia and proteinuria of nephrotic patients we found in a
      previous study. After an 8-week baseline period on free diet, patients were
      randomly allocated either on soy diet alone (SD) or to SD plus 5 g/day of fish
      oil (SD + FO) orally for two months. Then they crossed over to the other
      treatment for two additional months. They finally resumed eating the free diet
      for 3 months. We selected 20 outpatients with chronic glomerulonephritis,
      proteinuria in the nephrotic range, fasting serum cholesterol > 250 mg/dl, mean
      serum creatinine concentrations 1.75 +/- 0.23 mg/dl. Serum lipid profile, urinary
      protein loss and nutritional parameters were monitored. With the soy diet, we
      obtained a significant decrease both of hyperlipidemia and of proteinuria. The
      effect of the soy diet on proteinuria increased over the 4 months. The addition
      of a moderate amount (5 g/day) of fish oil in a randomized cross-over design had
      no further beneficial effect. Stability of serum albumin, transferrin and the
      body mass index documented good nutritional status. In conclusion, the dietary
      manipulation with our vegetarian soy diet confirmed the beneficial effects on
      hyperlipidemia and proteinuria of nephrotic patients. Such effects persisted and
      even ameliorated after 4 months of diet. The addition of moderate oral
      supplements of fish oil did not potentiate the beneficial effect.

PMID- 8299239
TI  - Pressure natriuresis following therapy for "one-clip one-kidney" hypertension in
      man.
AB  - Decreased renal tubular reabsorption of sodium in response to increased renal
      artery perfusion pressure, or "pressure natriuresis", has been demonstrated
      directly in animal experiments but not in man. In bilateral or single-kidney
      renovascular hypertension, hypertension has been attributed to reduced pressure
      natriuresis, and a similar mechanism may operate in chronic renal failure. We
      report a patient who presented with bilateral renovascular disease and was
      treated initially by unilateral nephrectomy. At a second operation the remaining
      ischemic kidney was revascularised. There followed a dramatic natriuresis,
      sufficient to cause clinical and biochemical features of hypovolemia. However,
      despite the natriuresis, systemic blood pressure remained elevated in the few
      weeks following surgery. We attribute the natriuresis to increased renal artery
      perfusion pressure, and conclude that acute pressure natriuresis sufficient to
      over-ride neurohormonal antinatriuretic mechanisms does occur in man. However,
      the failure to normalize blood pressure acutely following the natriuresis
      suggests that decreased sodium excretion is not the only mechanism which
      maintains hypertension in this unusual syndrome.

PMID- 8299240
TI  - Enhanced activity of sympathetic renal nerves in hypertensive patients with
      unilateral renal ischemia--its relationship to plasma renin activity in renal
      venous blood.
AB  - In 16 hypertensive patients with significant unilateral renal artery stenosis
      plasma renin activity (PRA) and plasma levels of adrenaline (A), noradrenaline
      (NA) and dopamine were assessed in arterial blood, renal venous blood of the
      ischemic (IK) and normally (NK) perfused kidney and in blood withdrawn from the
      inferior vena cava, distally from the orifices of the renal veins. Plasma levels
      of A (= 661.8 +/- 187.7 pg/ml) and NA (= 396.3 +/- 72.5 pg/ml) in renal venous
      blood of the ischemic kidney were significantly greater than in renal venous
      blood of the normally perfused kidney (A = 123.4 +/- 16.0 pg/ml; NA = 277.2 +/-
      55.6 pg/ml) and than in arterial blood (A = 68.44 +/- 8.4 pg/ml; NA = 192.8 +/-
      28.9 pg/ml) and inferior vena cava blood (A = 67.8 +/- 7.5 pg/ml; NA = 182.6 +/-
      26.8 pg/ml). In contrast to A and NA, plasma D level in renal venous blood of the
      normally perfused kidney was significantly higher (= 27.9 +/- 4.9 pg/ml) than in
      renal venous blood of the ischemic kidney (= 14.3 +/- 2.1 pg/ml) and than in
      arterial blood (= 16.1 +/- 1.9 pg/ml) and in blood of the inferior vena cava (=
      16.3 +/- 1.8 pg/ml). A significant positive correlation was found between PRA and
      plasma levels of A and NA respectively only in renal venous blood of the ischemic
      kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299241
TI  - Bone marrow function during quadruple immunosuppressive therapy after renal
      transplantation.
AB  - Bone marrow function was evaluated in 50 patients treated with quadruple
      immunotherapy (prednisone, azathioprine, anti-lymphocyte globulin [ALG] until
      creatinine clearance > 10 min, cyclosporine thereafter) after renal
      transplantation. Thrombocytopenia (< 100 mio./ml) developed in 30% of patients
      and leucopenia in 4%. Leucopenia was always accompanied by thrombocytopenia.
      Thrombocytopenia usually developed within 3 days of the operation. The most
      significant factors in the development of thrombocytopenia were ALG treatment and
      a low platelet count (< 250 mio./ml) on admission. The toxic effect of ALG was
      immediate, but disappeared within 5 days of ALG discontinuation. Other factors of
      importance were female sex, low weight (< 70 kg) and long (> 1 year) dialysis
      duration. Cyclosporine had no toxic effect. Azathioprine treatment played only a
      minor role in the development of thrombocytopenia but patients with low (100-200
      mio./ml) and falling platelet counts who later developed thrombocytopenia were
      treated with significantly (p < 0.01) higher azathioprine dosages. The present
      study suggests that thrombocytopenia incidence can be reduced if azathioprine
      treatment is reduced to 1 mg/kg/day under the following circumstances: 1) small
      female patients; 2) platelet count < 250 mio./ml on admission; 3) platelet count
      < 200 during admission and falling. ALG treatment should usually be limited to 14
      days, but azathioprine dosage can safely be increased after ALG discontinuation.

PMID- 8299242
TI  - The effects of cyclosporin on renal microsomal cytochrome P-450 systems.
AB  - The effect of CsA on the renal microsomal cytochrome P-450 system was examined by
      using two animal models. Male Lewis rats and male white rabbits were treated with
      olive oil alone (Group A) or with CsA (30 mg/kg/day, Group B) by oral gavage for
      7 and 14 days. Blood urea nitrogen and serum creatinine levels were determined at
      serial intervals after administration of CsA. In rats, BUN and S-Cr were
      increased, indicating the development of nephrotoxicity in group B by the 14th
      day after administration; BUN 78.8 mg/dl, S-Cr 3.2 mg/dl, but not in group A (BUN
      29.3 mg/dl, S-Cr 0.7 mg/dl). In the rabbit experiments, BUN and S-Cr
      significantly increased in group B after 7 days of treatment but not in group A.
      P-450 content of the kidney microsomes prepared from rat and rabbit was examined.
      The renal specific P-450 content in group A was 68.8 pmol/mg protein in rats and
      52.1 pmol/mg protein in rabbits, whereas those in group B showed 135.6 and 221.0
      pmol/mg protein at day 14, respectively. SDS-PAGE also showed a significant
      increase in the content of P-450 after the CsA administration. Kidney microsomal
      aminopyrine N-demethylase activities were increased about 2.5 and 1.7 fold in
      rats and in rabbits, respectively. Monooxygenase activities for laurate and
      prostaglandin A1 were not significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299243
TI  - The influence of recipient and donor age on the outcome of renal transplantation.
AB  - This paper assesses the impact of age on the outcome of cadaveric renal
      transplantation. Data are presented on 99 consecutive patients undergoing first
      renal allografts at one unit. Patients are divided into those aged less than 50
      (n = 53), patients between 50 and 60 (n = 16), and those aged 60 years and over
      (n = 30). There was no significant difference in graft survival at one year
      between the three groups. There was however an increased mortality with
      increasing recipient age (1.9%, 12.5% and 20.0% respectively for each age group).
      The effect of increasing donor age on graft survival was also studied. Graft
      survival at two years for first grafts was not influenced by donor age. We
      conclude that age alone is not a criterion for exclusion of patients from
      transplant programs. In addition we provide data to support the use of elderly
      donors as a potential source of cadaveric renal grafts for certain patients.

PMID- 8299244
TI  - Acute hemorrhage from a pyelocaliceal diverticulum of a native kidney in a renal
      transplant patient.
AB  - A 28-year-old renal transplant patient developed a shock due to an acute bleeding
      from his right native kidney. An urgent nephrectomy was performed. Macroscopic
      and histological examination revealed a pyelocaliceal diverticulum as the cause
      of the hemorrhage. This rare event must be taken into account in every case of an
      unexplained acute renal bleeding.

PMID- 8299245
TI  - Recurrent acute renal failure and polyps of the colon.

PMID- 8299246
TI  - Para-amino-benzoic acid (PABA) and chronic tubulointerstitial nephritis.

PMID- 8299247
TI  - Mesangial IgG in childhood minimal change disease.

PMID- 8299248
TI  - CD8 lymphocytes in polymyalgia rheumatica and giant cell arteritis.

PMID- 8299249
TI  - Pseudo Felty's syndrome. A polyclonal disease with a favorable prognosis. Report
      of two cases with Southern blot analysis of TCR.
AB  - The authors report two patients with large granular lymphocyte (LGL) expansion
      associated with rheumatoid arthritis corresponding to pseudo Felty's syndrome.
      These cells have natural killer and T cell surface antigen markers. LGL are a
      heterogeneous population and expansion of these cells is responsible for
      leukemia, which is generally a monoclonal proliferation. It has been suggested
      that Epstein-Barr virus (EBV) is a putative agent in this leukemia. No EBV DNA
      was found with a polymerase chain reaction analysis in the lymphocyte DNA of our
      two patients. Some cases of pseudo Felty's syndrome have exhibited a monoclonal
      pattern on Southern blot analysis of the T cell receptor. On the contrary, our
      two cases showed a polyclonal pattern with TCR beta chain Southern blot analysis.
      This fact, associated with the mild course seen in both over more than twenty
      years, suggest that pseudo Felty's syndrome is a disease with a good prognosis.

PMID- 8299250
TI  - Relationship between blood and joint tissue DHEAS levels in rheumatoid arthritis
      and osteoarthritis.
AB  - To assess the relationship between blood and tissue steroid levels, cortisol and
      dehydroepiandrosterone sulphate (DHEAS) were measured by radioimmunoassay (RIA)
      in blood and joint tissues from a group of patients with RA (N = 29) ranging in
      age from 26 to 80 years (mean 63, SD: 13) and another group with secondary
      osteoarthritis (OA; N = 23), ranging in age from 47 to 86 years (mean 66, SD: 9),
      all of whom were scheduled for surgical correction of joint dysfunction.
      Seventeen of the RA patients were on steroid treatment at the time of the study.
      Assessing all the patients together, it was found that the tissue concentrations
      of DHEAS very closely paralleled the blood levels (r = 0.875; p < 0.001). The
      mean blood and tissue concentrations of DHEAS were found to be significantly
      reduced in RA, compared to those in OA (geometric means 540 vs. 2100 nmol/l
      blood, respectively, and 160 vs. 420 nmol/kg tissue, p < 0.001). Individual data
      indicated, however, that: (a) 3/29 patients with RA exhibited normal levels; (b)
      the reduction was more accentuated in those patients on steroid treatment; and
      (c) 5/23 patients with OA, who were treated for cardiovascular disorders, also
      had reduced DHEAS levels. Significant differences were not found between the mean
      cortisol levels in RA and those in OA, nor was there a correlation between the
      blood and tissue levels of this steroid. The possible influence of reduced DHEAS
      levels on immune-mediated diseases and/or pathophysiology is unknown, and needs
      to be investigated.

PMID- 8299251
TI  - Radiologic features of DISH may mimic ankylosing spondylitis.
AB  - Intervertebral bony bridging and enthesopathy can occur in both diffuse
      idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) and we
      have seen difficulties in the radiological differentiation between them. We
      describe 6 patients selected because the bridges resembled syndesmophytes and
      this initially suggested a diagnosis of AS, although other considerations showed
      them to be part of the radiologic picture of DISH. The previously reported
      suggestions of the coexistence of DISH and AS are reviewed.

PMID- 8299253
TI  - EGF and EGF-r immunoexpression in Sjogren's syndrome secondary to rheumatoid
      arthritis. Correlation with EBV expression?
AB  - Minor labial salivary gland biopsies from 25 patients with secondary Sjogren's
      syndrome (SS) suffering from rheumatoid arthritis and from 11 patients
      complaining of ocular dryness associated with rheumatoid arthritis without proven
      SS, were studied for the immunohistochemical expression of Epidermal Growth
      Factor (EGF) and its receptor (EGF-r). Minor labial salivary glands from 11
      healthy individuals were used as the control. Furthermore, the results were
      correlated with data retrieved from a previous study on EBV expression by the in
      situ hybridization method in the same specimens. In 16/25 cases of secondary SS
      the epithelial duct cells expressed both EGF and EGF-r, particularly in the areas
      of lymphoepithelial lesion and tissue destruction. Eleven of these cases
      expressed a positive EBV hybridization signal. In contrast, only 3/11 patients
      with ocular dryness and 2/11 cases from the group of healthy individuals showed
      immunoreactivity for EGF/EGF-r. A positive EBV signal was detected in 3/11 and
      1/11 of these cases, respectively. These results indicate that EGF and EGF-r may
      play a crucial role in the evolution of the disease under the constant influence
      of EBV, which seems to up-regulate the expression of the EGF/EGF-r system.

PMID- 8299252
TI  - Increased risk of Pneumocystis carinii pneumonia in patients with Wegener's
      granulomatosis.
AB  - Combining cyclophosphamide (Cy) and corticosteroids has dramatically improved the
      prognosis of Wegener's granulomatosis (WG). But this treatment carries the risks
      of severe infectious complications and drug toxicity. During a 10-month period,
      we observed 6 cases of Pneumocystis carinii pneumonia (PCP) in 23 patients with
      biopsy-proven WG and renal involvement. These 23 patients were enrolled in a
      multicenter controlled clinical trial designed to evaluate the efficacy and
      safety of either intermittent high-dose pulse Cy or daily oral low-dose Cy in
      combination with oral prednisone. Mean delay of onset of PCP was 2.5 months after
      the beginning of the immunosuppressive therapy. In all cases, the diagnosis of
      PCP was established by cytological examination of bronchoalveolar lavage fluid.
      None of the patients experienced severe leukopenia at the time of diagnosis, but
      the mean lymphocyte count decreased to 495/mm3 (range 100 to 830/mm3) and 2
      patients had inverted CD4/CD8 T-cell ratios. Renal function was significantly
      impaired (creatininemia = 493.5 vs 195.4 micromol/l; p = 0.03) in the 6 patients
      presenting PCP vs those without. High-dose co-trimoxazole therapy was successful
      in 3 patients, but 3 others who required mechanical ventilation died. Treatment
      of WG with daily prednisone and either pulse or oral Cy may have contributed to
      higher rates of PCP in the past than previously thought and, therefore, patients
      currently receiving such a regimen may be at greater risk for PCP. For these
      patients, this opportunistic infection must remain highly suspect in order to
      reach a diagnosis earlier and rapidly initiate treatment. In addition,
      recommendations for prophylactic therapy are needed.

PMID- 8299254
TI  - The sensitivity and specificity of reduced CD8 lymphocyte levels in the diagnosis
      of polymyalgia rheumatica/giant cell arteritis.
AB  - The aim of this study was to determine whether the sensitivity and specificity of
      measuring CD8+ T lymphocyte percentages and numbers could be diagnostically
      useful in the assessment of polymyalgia rheumatica/giant cell arteritis
      (PMR/GCA). Double immunofluorescence and FACScan analysis were used to identify
      and quantify the CD3+CD8+ lymphocyte population. The absolute cell numbers were
      determined by a Coulter Counter. Random disease controls were used for comparison
      with 30 patients diagnosed as PMR/GCA. Both the percentage of CD3+CD8+ cells
      (17.4% PMR/GCA group vs 30.5% control) and the absolute numbers of CD8+
      lymphocytes (310 cell/ml PMR/GCA vs 723 cells/ml control) were significantly
      reduced (p < 0.001) in the PMR group. The sensitivity of reduced CD8+ percentages
      for diagnosis was 73% and the specificity was 85%. Analysis of likelihood ratios
      showed that CD8+ lymphocyte percentages < 22.15% were five times more likely in
      patients with PMR/GCA than in controls. Data suggested that reduced CD8+
      lymphocyte levels may be useful in the initial clinical assessment of patients
      with PMR/GCA. Only a larger study can establish whether these parameters should
      be used as diagnostic criteria.

PMID- 8299255
TI  - Distal metacarpal bone mineral density by dual energy X-ray absorptiometry (DEXA)
      scan. Methodological investigation and application in rheumatoid arthritis.
AB  - Dual energy X-ray absorptiometry scanning was performed along the axis of the
      third metacarpal bone of the non-dominant hand and including metacarpal bones 2,
      3, 4 and 5. The Bone Mineral Density (BMD) was calculated for the distal 1/4 of
      each metacarpal bone. Ten patients with seropositive, erosive rheumatoid
      arthritis (RA) and 10 healthy, sex- and age-matched persons were investigated
      twice. The average BMD in RA patients was 73.6% of the value found in normals.
      The coefficient of variation on double determinations (in patients and controls)
      was 0.9-3.0%. We suggest that dual energy X-ray absorptiometry scanning with the
      scanning procedure proposed here may be an important instrument for the
      quantification of disease progression.

PMID- 8299256
TI  - Low molecular weight IgM in primary Sjogren's syndrome.
AB  - Low molecular weight IgM (LMW IgM), the monomeric subunit of pentameric IgM, was
      measured in the serum of 27 patients with primary Sjogren's syndrome. LMW IgM was
      also measured in a control group consisting of 24 patients with psoriatic
      arthritis (PA) and 8 patients with active rheumatoid arthritis (RA). LMW IgM was
      found in the majority of patients with primary SS (63%) and those patients had a
      longer disease duration than those without SS (80.7 +/- 43.9 months vs 37 +/-
      18.3, p = 0.01). Although the differences were not significant, SS patients with
      LMW IgM showed higher rates of: seropositive disease (71% vs 50%), anti-Ro (59%
      vs 30%) and anti-La antibodies (12% vs 0%), extraglandular involvement (76% vs
      60%) and raised gammaglobulins levels (47% vs 30%) compared to those without LMW
      IgM. Our only two patients with active RA and vasculitis had LMW IgM. None of the
      patients with PA showed LMW IgM, regardless of their Kammer subgroup
      classification, disease activity or radiological evidence of erosions. The
      presence of LMW IgM in a high percentage of patients with primary SS appears to
      be the expression of a dysregulation of B cell state that may predispose these
      patients to developing malignant lymphoproliferation.

PMID- 8299257
TI  - Correlations between clinical facets of outcome in rheumatoid arthritis.
AB  - At 8-year follow-up of 103 patients with rheumatoid arthritis, an X-ray index
      based on Larsen's score for the hands, wrists, ankles and feet showed a high
      correlation with the joint score (0.75 by Spearman's rank correlation), the
      function score (0.68), ESR (0.61), and CRP (0.64). These results suggest that
      Larsen's method of scoring both the hands and feet is a valid single method to
      assess long-term outcome in rheumatoid arthritis.

PMID- 8299258
TI  - Anti-RA 33 as a marker antibody of rheumatoid arthritis in a Finnish population.
AB  - To obtain information on anti-RA 33 as a marker antibody of rheumatoid arthritis
      (RA), a panel of Finnish sera were tested by immunoblotting with partially
      purified RA 33 antigen. Six of 100 specimens from patients with RA, one of 39
      specimens from subjects who later developed seropositive RA, and one of 50
      specimens from subjects with "false-positive" rheumatoid factor reactions were
      positive. The findings are compatible with the concept that anti-RA 33 is
      associated with RA from its onset and can even precede the disease. However, the
      prevalence of this antibody in Finnish RA patients is remarkably low compared to
      patients from continental Europe.

PMID- 8299259
TI  - Influence of disease activity on steroid hormone levels in peripheral blood of
      patients with rheumatoid arthritis.
AB  - The steroid hormone status of 27 female patients (15 premenopausal and 12
      postmenopausal) and 11 male patients with rheumatoid arthritis (RA) was
      investigated before and after a clinically significant deterioration in disease
      activity. In postmenopausal patients the serum level of cortisol decreased
      significantly with the progression of disease activity. No significant change in
      the serum levels of oestrone, oestradiol, androstenedione,
      dehydroepiandrosterone, dehydroepiandrosterone sulfate or prolactin was found
      within the groups. In premenopausal patients serum cortisol levels also
      decreased, with progression of disease activity, but this difference did not
      reach statistical significance. In male patients with RA none of the measured
      steroid hormone levels changed significantly after exacerbation of disease
      activity. Our data indicate that the synthesis and/or utilization of cortisol
      might be abnormal in female patients with active rheumatoid arthritis.

PMID- 8299260
TI  - Catastrophic antiphospholipid syndrome (CAS): a rare manifestation of the
      antiphospholipid antibody syndrome.
AB  - During the last decade, antiphospholipid antibodies and their clinical
      manifestations have given rise to increasing interest and have been associated
      with a wide spectrum of clinic expression, including arterial and venous
      thrombosis, thrombocytopenia, recurrent fetal wastage, Coombs positive
      haemolysis, livedo reticularis and neurological abnormalities, commonly present
      as isolated recurrent events, and rarely characterized by fatal outcome.
      Recently, an acutely disseminated vasculopathy, the so-called "catastrophic
      antiphospholipid syndrome" (CAS) characterized by non-inflammatory vascular
      occlusion and frequency of fatal outcome, has been described. We present yet
      another case report of this new and poorly understood entity and review its
      antecedents, clinical manifestations, serological profile, treatment and outcome.

PMID- 8299261
TI  - Adult Still's disease and inflammatory myositis.
AB  - Although myalgias occur often in adult onset Still's disease (AOSD), inflammatory
      myositis is rare. We describe a 41-year-old female with AOSD, who had clinical,
      enzymatic, electromyographic and pathological evidence of myositis, fulfilling
      the diagnostic criteria for polymyositis. To our knowledge, this exceptional
      association has only once been reported before.

PMID- 8299262
TI  - Jaccoud's arthropathy and psoriatic arthritis.
AB  - A patient with long-standing psoriatic arthritis developed an arthropathy of the
      hands characterized by subluxations of the metacarpophalangeal joints without
      erosive changes. This is to the best of our knowledge the first reported case
      describing Jaccoud's arthropathy associated with psoriatic arthritis.

PMID- 8299263
TI  - Suprascapular nerve entrapment of occupational etiology: clinical and
      electrophysiological characteristics.
AB  - In this paper we report the clinical and electrophysiological study of a patient
      with suprascapular nerve entrapment. The patient was initially diagnosed as
      having shoulder pain due to tendinitis, since his job involved continuous loading
      of the affected shoulder with heavy weights. Later, clinical exploration revealed
      wasting of the supra and infraspinatus muscles. Electrophysiological study
      confirmed the diagnosis of a neuropathy of the suprascapular nerve at the level
      of the coracoid notch, which improved with conservative treatment. This case
      report stresses the importance of suprascapular nerve entrapment as a causal
      factor for shoulder pain; it has an occupational origin which should be taken
      into account in the differential diagnosis of shoulder pain syndromes.

PMID- 8299264
TI  - Juvenile chronic arthritis: a biobehavioral disease. Some unsolved questions.
AB  - This review presents a multidimensional biopsychosocial model suitable for
      evaluating medical and psychosocial empirical findings in juvenile chronic
      arthritis (JCA). The possible predisposing, provoking and modifying variables
      that have been assessed in studies of JCA are presented, together with
      suggestions for further research. The model is appropriate for structuring and
      validating data in future longitudinal studies and may also serve as a frame of
      reference for a multi-professional team approach in the care of rheumatic
      children and their families.

PMID- 8299265
TI  - Localized scleroderma after infection with Epstein-Barr virus.
AB  - Over a period of three years (1989-1992) five children suffering from localized
      scleroderma were seen at the Department of Pediatrics of the University of
      Trieste. Evidence of a previous infectious mononucleosis (IM) was present in four
      out of five patients. The clinical history of these four children is reported.
      The association between the appearance of scleroderma and a previous viral
      infection is not surprising. However, in the pediatric literature there is only
      one case of progressive systemic sclerosis (PSS) developing in a 15-month-old
      girl less than one month after she contracted IM. The presence of shared epitopes
      between an Epstein-Barr virus protein, BOLF1, and the hypervariable region of HLA
      associated with the pauciarticular form of JCA, recently reported, could provide
      a key to the pathogenesis of other collagen diseases such as scleroderma.

PMID- 8299266
TI  - Sarcoidosis of early onset. A challenge for the pediatric rheumatologist.
AB  - The clinical picture of twelve patients with sarcoidosis commencing under 4 years
      of age is presented. Follow-up ranged from 5 to 30 years with a mean of 11.5
      years. Two patients were mother and daughter, the other cases were sporadic. All
      children developed the typical symptom triad of rash, polyarthritis and uveitis
      with onset before their 4th birthday. Further symptoms comprised fever,
      hepatosplenomegaly, parotid swelling and hypertension. Eight patients suffered
      from cardiac and four from cerebral involvement; one girl died from cerebral
      involvement at the age of 12. Two developed severe lung changes. The prognosis
      was poor with sequelae in all patients. Several children seem to have improved on
      immunosuppressive therapy. Early onset sarcoidosis is a multisystemic
      granulomatous disease; since polyarthritis is a dominant manifestation, many
      patients are diagnosed as having juvenile chronic arthritis. The early onset form
      must be distinguished from later onset sarcoidosis, which mainly affects children
      over 8 years of age or young adults. The disease types differ in their
      presentation, symptoms, course and prognosis; some of the clinical features and
      the histology, however, are identical.

PMID- 8299267
TI  - Indications for starting or changing disease modifying anti-rheumatic drugs in
      rheumatoid arthritis patients.

PMID- 8299268
TI  - Does dapsone have a role in the treatment of temporal arteritis with regard to
      efficacy and toxicity?

PMID- 8299269
TI  - Captopril-induced lupus.

PMID- 8299270
TI  - Fibromyalgia, antinuclear antibodies and clinical features of connective tissue
      disease.

PMID- 8299271
TI  - Massive splenomegaly: a manifestation of active systemic lupus erythematosus.

PMID- 8299272
TI  - [Late deterioration of functional abilities in adult cerebral palsy].
AB  - Clinical characteristics of late deterioration in adult cerebral palsy were
      reported with detailed neurological evaluations and analyses. 10 adult cases, 9
      male and 1 female, with cerebral palsy (CP) were included aged from 24 to 58
      years on admission. Without marked mental retardation all had been ambulant and
      completely independent of ADL with residual spasticity and/or dyskinesia of
      minimal degree until the second or third decade. Late deterioration of functional
      abilities starting with numbness or pain in upper extremities at age 24-45 (mean:
      36.2 y), associated with profound atrophy of the shoulder girdle and hand
      muscles. Dyskinesia and spasticity markedly aggravated with urinary and
      respiratory dysfunctions, resulting in tetraplegia in a couple of years.
      Mentality is generally unaffected, however, severe dementia occurred in one case.
      Intensive clinical examinations revealed no particular abnormalities except for
      mild segmental neurogenic changes by needle EMG. Neuroradiological surveys
      revealed a marked narrowing of upper to middle cervical spinal canal with
      deformity and shrinkage of the corresponding cord in most cases. Cranial CT scans
      and MRI were unremarkable except for diffuse cortical atrophy and ventricular
      dilation. These studies showed that in adult CP an unexpectedly severe
      deterioration of sensory, motor and/or mental functions may appear even in
      previously well achieved cases. These dramatic changes of the clinical features
      of CP after middle age might be suggestive of the degenerating process and
      precocious aging of the CNS.

PMID- 8299273
TI  - [The significance of cervical collaterals in the subclavian steal phenomenon].
AB  - The subclavian steal syndrome (SSS) is often associated with occlusive disease
      involving the subclavian or innominate arteries, but an asymptomatic subclavian
      steal, called the "subclavian steal phenomenon" (SSP), is not uncommon. Though
      intracranial collaterals had been postulated as one of the etiologies for the
      SSP's being asymptomatic, little has been accomplished in the investigation of
      extracranial channels. To study the hemodynamic role of cervical collateral
      channels, an angiographical study was done in three cases with SSP. The three
      cases were admitted to the hospital because of carotid ischemic symptoms, such as
      right hemiplegia or sensory aphasia. Each case had a blood pressure difference
      between the two arms, but in all of them the past history or the exercise test
      was negative for vertebrobasilar or arm ischemia. On angiography, occlusions of
      the unilateral proximal subclavian artery, the left in case 1 and the right in
      case 2, or a tight stenosis of the innominate artery was found in case 3. In each
      case, the vertebral artery flow in the affected side was inverted, siphoning off
      from the opposite vertebral artery into the affected subclavian artery. In
      addition to the vertebral siphoning; muscular branches of ipsilateral external
      carotid origin in cases 1 and 2, or the thyrocervical trunk via the inferior
      thyroid artery in case 3 was also found to function as a collateral channel to
      the vertebral artery on the affected side.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299274
TI  - [FDG-PET in an amnestic and hypersomnic patient with bilateral paramedian
      thalamic infarction].
AB  - A 67-year-old patient was admitted to our hospital owing to coma and tetraplegia.
      MRI showed T2 weighed high intensity areas in the pontine tegmentum, lower aspect
      of the right cerebellar hemisphere, left half of medulla oblongata, and bilateral
      paramedian thalamus. He showed marked recovery by urokinase injection becoming
      able to walk in a few months, but severe amnesia and hypersomnia persisted even 5
      months after onset. EEG showed diffuse alpha activity with occasional delta waves
      in frontal leads. Intelligence was considered normal (WAIS score; verbal IQ 97,
      performance IQ 102, total IQ 99), through performance on Wechsler memory Scale-R
      (Revised Japanese edition, WMS-R) and Benton Visual Retention Test indicated
      impairment of both verbal and visual memory. Verbal memory was impaired to a
      greater degree than visual memory (Scores of WMS-R: verbal memory index 60,
      visual memory index 98, index of general memory 72, attention index 95, index of
      delayed memory 71). He was able to finish only 0 and 1 categories on two trials
      of the Wisconsin Card Sorting Test. FDG (18F-fluorodeoxyglucose)-PET showed
      diffuse areas of decreased metabolism in bilateral thalami, frontal lobes,
      cingulate gyri and medial temporal lobes. The bilateral thalamic lesion seemed to
      affect the following structures, as judged from MRI: 1) The anterior thalamic
      peduncle including most of the reciprocal connections between dorsomedial nucleus
      of thalamus (MD nucleus) and the frontal lobe, 2) The inferior thalamic peduncle
      which serves as the reciprocal pathway between MD nucleus and medial temporal
      lobe, especially the amygdala (component of Yakovlev circuit), and 3) The
      inferior part of mammillothalamic tract (component of Papez circuit).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8299275
TI  - [A case of hereditary motor and sensory neuropathy (HMSN type 2) with bilateral
      recurrent nerve palsy].
AB  - An atypical case of hereditary motor and sensory neuropathy (HMSN) type 2 with
      cerebellar ataxia, hand tremor and bilateral recurrent nerve palsy was described.
      The patient was a 57-year-old man who complained of dyspnea, stridor , hoarseness
      during exercise and snored heavily during sleep since he was 20 years old. These
      symptoms and signs were slowly progressive. He had difficulty in breathing even
      at resting state when he was 54 years old and since then, he noticed muscle
      wasting of his hands and feet. Neurological examinations on admission revealed
      pes cavus, scoliosis, distal muscular atrophy in his four extremities, especially
      severe in bilateral lower limbs. Deep tendon reflexes were diffusely depressed.
      The fiberscopic examination demonstrated the limitation of bilateral vocal cord
      abduction and his tongue was slightly atrophic. Fine postural tremor was found in
      bilateral hands. Mild limb and truncal ataxias were also noted. Blood pCO2 level
      was elevated to 66% although FEV1.0% and vital capacity were within normal
      limits. Peripheral nerve conduction velocities were almost normal, though distal
      terminal latencies were slightly prolonged and amplitudes of evoked potentials
      were markedly decreased. The sural nerve biopsy studies revealed the chronic
      axonal or neuronal degeneration of both large and small myelinated fibers. From
      the clinical, electrophysiologic and histopathologic findings, the diagnosis of
      HMSN type 2 with bilateral recurrent nerve palsy and other atypical neurological
      findings was made. It is practically important to evaluate the presence or
      absence of vocal cord paralysis in the patients with HMSN from clinical
      viewpoints.

PMID- 8299276
TI  - [Phenylketonuria with adult-onset neurological manifestation].
AB  - We report a male patient with phenylketonuria (PKU) who developed multisystem
      neurological manifestation in his fourth decade. He was born in 1957 when a
      neonatal mass screening had not been available. His neuropsychological
      development was entirely normal and he was a good athlete during his high school
      days. He was in good health until the age of 32, when his vision was blurred. In
      four months his gait progressively deteriorated to bind him to a wheel chair. On
      physical examination he had red hair and gray eyes. IQ was 68. Visual field
      showed concentric narrowing and his visual acuity was 0.2/0.3 (2.0/2.0). The
      limbs were spastic and weakened. He complained of pain in the extremities. He
      suffered from pollakisuria. Routine blood tests and CSF findings were normal. He
      was also found to be normal in peripheral nerve conduction studies and central
      conduction studies of SEP and VEP. EEG showed diffuse slowing in background
      activities. T2-weighted MRI of the head revealed widespread high-intensity areas
      in the deep white matter especially in bilateral occipital lobes. Serum aminogram
      disclosed the remarkably elevated phenylalanine (Phe) level to 1663 nmol/ml
      (normal range 50-90) and reduced tyrosine. Urinary secretion of endogenous
      tetrahydroxy-biopterin (BH4; coenzyme of Phe hydroxylase) remained in a normal
      range, and oral administration of 100 mg/kg of BH4 failed to normalize the serum
      Phe level. Despite a strict dietary control (oral intake of Phe less than 0.5
      g/day), the serum Phe level remained high around 500 nmol/ml and his neurological
      deficits still deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299277
TI  - [A case of progressive systemic sclerosis with Sjogren's syndrome presenting with
      coma, convulsion and bilateral thalamic hypodensity on computed tomography].
AB  - A 35-year-old female with progressive systemic sclerosis (PSS) and Sjogren's
      syndrome developed consciousness disturbance and generalized seizure after the
      episode of fever and erythema lasting for 3 weeks. Neurological examination
      disclosed deep coma and spastic tetraplegia with pathological reflexes.
      Laboratory data showed mild anemia, severe hypoproteinemia, hypoalbuminemia and
      increase of protein content in the cerebrospinal fluid. Cranial CT scans obtained
      after convulsion revealed diffuse brain swelling and bilateral symmetrical
      hypodensity involving the thalami and posterior limbs of the internal capsule.
      High-dose corticosteroid therapy and osmotherapy with correction of hypovolemia
      were started, because severe dehydration, hypoalbuminemia and cerebral vasculitis
      were suspected to change the vascular permeabilities. Neurological symptoms and
      CT findings were rapidly improved. Cerebral angiography 4 weeks after convulsion
      showed definite angitis. The patient was discharged 9 weeks after convulsion. In
      our case, a possible cause of the characteristic CT findings may be the
      disturbance of cerebral venous return due to hypovolemia and vasculitis. High
      dose corticosteroid therapy may be recommended in patients with collagen disease,
      who show the bilateral symmetrical thalamic hypodensity on CT scans.

PMID- 8299278
TI  - [A case of radiation myelopathy with characteristic findings of thermoregulatory
      sweat distribution and magnetic resonance images].
AB  - A 73-year-old man had undergone resection of a lung carcinoma of the right upper
      lobe in 1987. Post-operative irradiation (40 Gy) was given to the right hilus. In
      November 1988, recurrence was detected in the trachea. Laser therapy was done in
      December 1988. From January 9 to February 13 in 1989, irradiation (50 Gy) was
      given to the mediastinum. From the beginning of 1991, the patient developed
      muscle weakness in the right lower extremity and pain temperature sensations were
      impaired below the Th12 level on the left side. On October 3, 1991, he was
      admitted to our hospital. Neurological examination revealed mild muscle weakness
      in the right lower extremity. Superficial sensations were impaired below the Th6
      level bilaterally. Deep tendon reflexes were hyperactive in the lower
      extremities. A bilateral Babinski sign was positive. The T1 weighted MRI showed a
      low signal intensity in the spinal cord at the level of thoracic vertebra (TV)2
      TV6. T2 weighted images revealed a high signal intensity area of the spinal cord
      from TV4-TV6. A gadolinium-DTPA injection revealed an enhancement on the left
      side of the spinal cord at the TV2-3 level, and right side of the spinal cord at
      the TV4-5 level on the sagittal and axial images. A thermal sweating test
      revealed hypohidrosis below the Th8 level on the right side, and the Th11 level
      on the left side. Sweating was delayed at the Th7-8 levels on the right side and
      Th10-11 levels on the left side. An irradiated field on the chest revealed
      hypohidrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299279
TI  - [A case of pontine infarction with persistent primitive proatlantal artery].
AB  - A 61-year-old woman was admitted to the hospital on September 18, 1991 because of
      left hemiparesis, dysphagia, and dysarthria since five days before. She was
      formerly pointed out diabetes mellitus and hypertension, but she did not receive
      any treatment. The MRI showed a high signal area in the right paramedian portion
      of the upper pons on T2 weighted image and proton image. The angiography showed
      that persistent primitive proatlantal artery originated from the left internal
      carotid artery and joined to the horizontal portion of the left vertebral artery.
      The image of carotid-vertebrobasilar system and proatlantal artery showed so
      severely arteriosclerotic. This is the first report of brainstem infarction with
      persistent primitive proatlantal artery. In this case, the pontine infarction was
      thought to occur on the basis of the arteriosclerosis of blood vessels and change
      of blood flow of carotid-vertebrobasilar system due to persistent primitive
      proatlantal artery.

PMID- 8299280
TI  - [A case of deletion of the short arm of chromosome 18 associated with chronic
      polymyositis].
AB  - A case of deletion of the short arm of chromosome 18 (18p- syndrome) associated
      with chronic polymyositis is described. The patient was a 37-year-old woman, who
      had psychomotor retardation in her early childhood. She started to notice a
      difficulty in raising both arms at 14 years of age and furthermore, she developed
      a gait disturbance due to weakness of the proximal muscles of the lower
      extremities from 34 years of age. Her parents were first cousins. On physical
      examination, she showed many dysmorphic features, such as short stature, round
      face, hypertelorism, low nasal bridge, small chin, high arched palate, abnormal
      dentition, short and webbed neck, and broad chest. Neurological examination
      revealed a low intelligence (IQ 47), severe proximal muscle weakness with
      moderate proximal muscle atrophy in all extremities, a waddling gait, and
      decreased or absent deep tendon reflexes of all extremities except for bilateral
      ankle jerks. Serum creatine kinase and myoglobin levels were slightly elevated.
      Needle EMG study showed fibrillation potentials at rest and polyphasic and low
      amplitude motor unit potentials of short duration on volitional activity in the
      affected muscles. Muscle biopsy demonstrated a variation in fiber size, necrotic
      fibers and mononuclear cell infiltration. These findings were compatible with
      those of chronic polymyositis. In addition, cytogenetic findings revealed
      46.XX.18p- karyotype, although her parents had no chromosome abnormality. She had
      no immunological abnormality except for a positive rheumatoid factor and
      elevation of CD4/CD8 ratio on lymphocyte subset analysis in peripheral
      blood.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299281
TI  - [Angiotropic lymphoma presenting with subacute dementia: treatment with
      combination chemotherapy (CHOP) based on antemortem diagnosis--a case report].
AB  - We report a 64-year-old male with angiotropic lymphoma. He developed subacute
      dementia with right hemiparesis. Laboratory abnormalities included elevated serum
      lactic dehydrogenase (LDH) (715 U/l) erythrocyte sedimentation rate (38 mm/hr)
      and CSF protein (90 mg/dl). Precontrast MR imaging of the brain demonstrated
      lesions involving the left internal capsule, subcortical white matter in the
      right frontal lobe and splenium within the atrophic corpus callosum. A brain
      biopsy revealed intravascular lymphoid cells, strongly suggestive of angiotropic
      lymphoma. By combination chemotherapy (CHOP), serum LDH and CSF protein
      normalized through the patient remained demented. He died of bronchopneumonia
      about 2 years and 5 months after the onset. Coronal sections of the brain showed
      infarct in the left internal capsule as well as markedly thin corpus callosum
      with necrotic lesions involving both the genu and splenium. Microscopic
      examination showed many small vessels occluded by lymphoma cells (B-lymphocyte)
      predominantly in the corpus callosum, cerebral white matter, thalamus, midbrain,
      medulla oblongata, thoracic and lumbar segments of the spinal cord. By
      combination chemotherapy, our patient survived longer than most of previous
      patients with angiotropic lymphoma. An early diagnosis and subsequent combination
      chemotherapy may improve neurological manifestations, and make possible longer
      survival in angiotropic lymphoma.

PMID- 8299282
TI  - [A case of Hashimoto's encephalopathy with a relapsing course related to
      menstrual cycle].
AB  - A case of 43-year-old woman with Hashimoto's encephalopathy who experienced three
      relapses closely associated with the menstrual cycle is reported. In April 1992,
      she began to experience occasional tremors in her arms. Three months later, she
      experienced a generalized seizure and was transferred to our hospital.
      Hashimoto's thyroiditis was diagnosed on the basis of high thyroid microsomal
      titer and mild hypothyroidism. Neurological findings in admission included action
      tremor in both hands, myoclonus in all extremities, cerebellar ataxia, confusion,
      and hyperreflexia. Cerebrospinal fluid showed elevated protein level without
      pleocytosis. Electroencephalogram showed diffuse slowing and magnetic resonance
      imaging of brain was normal. Hashimoto's encephalopathy was diagnosed from these
      findings. These episodes of remission and exacerbation were observed during the
      admission. Her symptoms started at ovulation, worsened during the luteal phase,
      and improved when menstruation started. After the third relapse, she was treated
      with oral thyroxine for hypothyroidism and with an estrogen and progesterone
      combination to regulate the menstrual cycle. Her thyroid function gradually
      became euthyroid and she did not experience any subsequent relapses. The relation
      between the relapsing course and menstrual cycle suggests that the periodic
      alteration of gonadotrophic and/or gonadal hormones or the menstrual regulating
      center itself in the brain may be an important factor of pathogenetic mechanism
      of the disorder.

PMID- 8299283
TI  - [Marginal white matter necrosis of the spinal cord].

PMID- 8299284
TI  - Transient global amnesia.
AB  - Transient global amnesia (TGA) is a transient, benign neurological syndrome,
      characterized by global loss of memory, preserved consciousness and self
      awareness, associated with some behavioral changes (in particular, repetitive
      questioning). It generally resolves within 24 h. Mild brain stem symptoms can
      often be demonstrated during the attack, but major neurological abnormalities
      never occur. The only sequel is a permanent amnesic gap for the duration of the
      episode. The episode is often preceded by typical precipitating events, such as
      physical activity, emotional stress, acute pain, comprising haemodynamic changes
      of the body. The diagnosis is easy provided one is acquainted with the syndrome.
      The prevalence of vascular risk factors is low and the risk for stroke is not
      increased. Although much evidence indicates the possibility of a causative
      ischaemia in the inferomedial parts of the temporal lobes, an atherothrombo
      embolic TIA is not the cause of TGA, and TGA is unrelated to cerebrovascular
      disease in general. In the author's view, the cause of TGA is a transient
      ischemic attack (TIA) but a haemodynamic one of the vertebrobasilar system,
      producing a transient dysfunction of inferomedial parts of the temporal lobes,
      regions that are particularly sensitive to impaired blood supply. For a full
      pathogenetic explanation of TGA, clarification of the underlying mechanisms is a
      prerequisite. This touches on the genesis of migraine and Leao's spreading
      depression phenomenon. The term 'amnesic TIA' would reflect the pathogenesis more
      appropriately.

PMID- 8299285
TI  - Soluble terminal complement components in human myasthenia gravis.
AB  - The loss of membrane acetylcholine receptor (AChR) leading to muscle weakness and
      impaired neuromuscular junction (NMJ) transmission in human myasthenia gravis
      (MG) is in part due to complement mediated muscle membrane damage. This has been
      supported by the histologic finding of C9 at the NMJ in human MG. We evaluated
      for evidence of terminal complement components in plasma by using an ELISA for
      SC5b-9 in 42 separate plasma samples from 31 patients with MG and from healthy
      controls. Abnormal elevations of SC5b-9 was found in 18 of 31 patients (58%) at
      one or more time points when plotted on a standard positive dilution curve.
      Multiple samples were available from 8 patients over time. Clinical deterioration
      in some, but not all, was accompanied by an increase in SC5b-9 values. There was
      no clear distinction in the group as a whole between MG severity or AChR antibody
      levels and SC5b-9 values. This supports the potential role of complement-mediated
      muscle membrane damage in the pathogenesis of human MG, but also demonstrates
      that plasma levels as measured by ELISA do not always correlate with disease
      activity.

PMID- 8299286
TI  - Surgery for intracranial meningiomas in elderly patients.
AB  - Ninety-three patients above 60 years of age underwent craniotomy for intracranial
      meningioma removal between 1980 and 1990 at the University Hospital Rotterdam.
      Sixty-four patients were 60-70 years of age, 29 were 70 years or older.
      Retrospectively, operative mortality, morbidity and outcome on discharge from
      hospital and at 6 months were assessed and correlated with age, sex, size and
      location of the tumor and preoperative neurological status. Seven patients (7.5%)
      had no or only minor symptoms, 68 (73%) had moderate neurological symptoms (able
      to live at home with some assistance) and 18 patients (19.5%) had severe symptoms
      and were dependent on assistance. Surgical mortality was 14%; after 6 months 17%
      of patients had died. Postoperative complications (surgical, medical or
      neurological) occurred in 41%. Neurological status 6 months after surgery was
      improved in 35 patients (38%), unchanged in 38 patients (41%) and worsened in 20
      patients (21%), 16 of whom had died. Outcome on discharge from hospital and after
      6 months correlated significantly with preoperative neurological status. There
      was no significant correlation with age, sex, size or location of the tumor.
      Removal of intracranial meningiomas in the elderly is associated with a high
      morbidity and mortality rate. However, a large number of elderly patients benefit
      from surgery for intracranial meningiomas, especially those patients with a good
      neurological preoperative status.

PMID- 8299287
TI  - Pure sensory stroke revealing a complex malformation of extra- and intracranial
      cerebral arteries.
AB  - Pure sensory strokes (PSS) are usually due to thalamic lacunar infarcts. We
      report a case of PSS in a 34-year-old female suffering from migraine who
      complained of sudden isolated left-sided paresthesia involving face, upper and
      lower limbs. We found a complex vascular abnormality associating internal carotid
      artery occlusion, posterior cerebral artery agenesia, aneurysm at the posterior
      face of the carotid siphon and angiomatous rete at the top of the basilar artery.
      The acquired origin of the carotid artery occlusion by possible neonatal
      dissection is probable since this patient has a permeable carotid canal on CT
      scan.

PMID- 8299288
TI  - Balo's concentric sclerosis diagnosed intravitam on brain biopsy.
AB  - A 28-year-old woman presented with acute right hemiparesis evolving to bilateral
      hemiplegia and a mute state within 1 week on a background of paranoid psychosis
      of 8 years duration. CT scan revealed multiple bilateral hypodense enhancing
      lesions in the central white matter. Biopsy of the lesion showed lamellar
      alternating zones of demyelination and remyelination, typical of Balo's
      concentric sclerosis, an acute variant of multiple sclerosis. Immunohistochemical
      staining for neurofilament showed greater damage to the axis cylinders by the
      disease than generally perceived by silver stains. Steroid therapy produced a
      gratifying and sustained improvement. Follow up CT scans and psychometry revealed
      regression of the demyelinating lesions and improvement of the cognitive state.

PMID- 8299289
TI  - Cheiro-oral-pedal syndrome in thalamic infarction.
AB  - Sensory disturbance around the corner of the mouth, in the palm of the hand and
      in the foot on the same side (cheiro-oral-pedal syndrome) has been reported only
      in 2 patients with brainstem lesion. We report 2 cases of cheiro-oral-pedal
      syndrome; the causative lesion was revealed by magnetic resonance imaging to be
      in the ventral postero-lateral and ventral posteromedial nuclei of the thalamus.

PMID- 8299290
TI  - The diagnosis and treatment of stroke in a patient with cancer: nonbacterial
      thrombotic endocarditis (NBTE): a case report and review.
AB  - Stroke in patients with cancer is different in terms of its etiology from stroke
      in the general population. Clinicians should be altered to the possibility of non
      bacterial thrombotic endocarditis (NBTE), associated coagulopathy, and viable
      treatment options. We review the case of a 42-year-old woman with cerivcal
      carcinoma and no risk factors for stroke who suddenly developed difficulty with
      speech and right-sided sensory changes. Her complete work-up and course are
      addressed.

PMID- 8299291
TI  - Acute febrile neutrophilic dermatosis (Sweet's syndrome) in neuro-Behcet's
      disease.
AB  - A case of Behcet's disease associated with Sweet's syndrome is presented. The
      onset was neurological symptoms and oral aphthae. Subsequently, genital ulcers
      developed. Coexistence of Sweet's syndrome and Behcet's disease has been reported
      only in few patients. On reviewing the literature, we propose that Sweet's
      syndrome is one of the associated diseases of Behcet's disease.

PMID- 8299292
TI  - X-linked adrenoleukodystrophy.

PMID- 8299293
TI  - Attitudes of asthmatic and nonasthmatic adolescents toward cigarettes and
      smoking.
AB  - A comparison study was made between attitudes of asthmatic and nonasthmatic
      adolescents toward cigarettes and smoking. Subjects were 67 asthmatic 9th- to
      12th-grade students, of whom 38 (57%) had active asthma with recurrent cough
      and/or dyspneic attacks and 29 (43%) had reactive airway disease and/or the least
      severe form of asthma expressed by recurrent cough. The control group included 62
      nonasthmatic students from the same high school. All subjects completed a
      questionnaire to determine attitudes, beliefs, and intentions regarding smoking.
      Their responses suggested that the group at highest risk of becoming smokers were
      those who had previously had asthma. The same adolescents had a more positive
      attitude toward cigarettes and smoking, a stronger intention to become smokers,
      and a self-image more closely linked with their perceptions of smokers. Thus,
      these adolescents may represent a high-risk group for becoming smokers in the
      future.

PMID- 8299294
TI  - Enteral theophylline and necrotizing enterocolitis in the low-birthweight infant.
AB  - In a two-phased retrospective study, clinical factors associated with the
      development of necrotizing enterocolitis (NEC) in neonates were identified. The
      first phase found 13 infants with NEC who had been treated more frequently with
      enteral theophylline (P < .025) and fed higher volumes (> 150 mL/kg/day; P < .05)
      than controls of comparable birthweight and postnatal age. Seven of the 13
      infants with NEC, weighing < 1,250 g at birth, had previously received
      intravenous aminophylline and been changed to enteral theophylline within six
      days before the onset of NEC. Prolonged rupture of membranes was more prevalent
      (P < .025) in infants with birthweight > 1,250 g who developed NEC in the first
      week of life. Maternal preeclampsia helped protect against the development of NEC
      (P < .05). In the second study phase, 59 infants with birthweights < 1,250 g were
      evaluated for gastrointestinal disturbance within five days of the introduction
      of any enteral medication. The frequencies of NEC, NEC scare, and feeding
      intolerance were greater in infants treated with enteral theophylline than in
      those treated with all other enteral medications combined (P < .05). This two
      phased study confirms the multifactorial etiology of NEC and indicates that the
      administration of enteral theophylline to young infants < 1,250 g may be a
      predisposing factor to GI disturbances and NEC. These findings warrant a further
      prospective investigation.

PMID- 8299295
TI  - The single-subject randomized trial. A useful clinical tool for assessing
      therapeutic efficacy in pediatric practice.
AB  - The purpose of a single-subject randomized trial is to assess objectively the
      efficacy of a specific therapeutic intervention in an individual patient.
      Treatment is randomly alternated with placebo over a number of study periods.
      Specific outcome measures are recorded blindly and later compared via paired
      statistical analysis. Single-subject trials have long been successfully performed
      in adults, but rarely in children. We present single-subject trials of two
      pediatric patients done to assess the effect of cisapride on symptoms arising
      from gastroesophageal reflux. In the first patient, the drug affected neither
      vomiting nor gagging, although stool frequency increased. Since the symptoms of
      concern were unaffected, cisapride was discontinued. In the second patient, use
      of cisapride led to a significant decrease in vomiting and wheezing; the drug was
      therefore incorporated into the therapeutic regimen. Single-subject randomized
      trials are inexpensive and simple and can be used by the family physician,
      pediatrician, or pediatric surgeon in daily practice. They permit the rational
      use of effective therapy and the abandonment of ineffective measures.

PMID- 8299296
TI  - Adolescent sexual activity.
AB  - Adolescents are becoming sexually active at younger ages. One half of the
      adolescents in the United States are sexually active. This article reviews
      adolescent sexual activity, including rates of sexual activity, sexual practices,
      gay and lesbian youth, and factors affecting the initiation of sexual activity.
      In addition, adolescent pregnancy, with possible outcomes and effects on teen
      parents and their offspring, is discussed.

PMID- 8299297
TI  - Infant botulism. A review of the literature.

PMID- 8299298
TI  - Pediatrician's role after hospital-based death and permanent disability in school
      aged children.

PMID- 8299299
TI  - Erythrocyte sedimentation rate. A valuable test in infants and children with
      sickle cell disease.

PMID- 8299300
TI  - Transient subcapsular cataract formation in a child with diabetes.
AB  - Transient cataracts in patients with insulin-dependent diabetes mellitus (IDDM)
      are rare and have been reported only in association with severe ketoacidosis or
      hyperosmolarity. We present an adolescent with transient bilateral posterior
      subcapsular cataracts, which developed after the recent onset of IDDM without
      ketoacidosis or severe hyperosmolarity.

PMID- 8299301
TI  - Miller Fisher syndrome, a brainstem encephalitis, mimics brain death.
AB  - Miller Fisher syndrome is a rare focal encephalitis of the brainstem
      characterized by cranial nerve palsy, ataxia, and areflexia. While this condition
      usually is mild and self-limiting, as this case documents, findings may fulfill
      many of the criteria in the clinical examination for brain death. Unlike brain
      death, however, it is not associated with irreparable structural damage of the
      brain or, as is mandatory, does it fulfill a very important prerequisite of brain
      death, the exclusion of potentially reversible causes of coma. Treatment of
      Miller Fisher syndrome is supportive.

PMID- 8299302
TI  - Methemoglobinemia due to skin application of benzocaine.
AB  - We report a 2-year-old child who presented with severe methemoglobinemia after
      topical application of Lanacane (with 3% benzocaine). The experience with our
      patient shows that intoxication can occur in children if the drug is applied to a
      large area of skin that has lost its integrity. We discuss the usefulness of the
      pulse oximeter in making the diagnosis and review the management of
      methemoglobinemia.

PMID- 8299303
TI  - Hypoglycemia due to sedation following clonidine test for growth hormone reserve.
AB  - Life-threatening hypoglycemia following insulin administration to assess growth
      hormone secretory capacity in children with hypopituitarism is well known. We
      report hypoglycemic convulsions in a child with congenital hypopituitarism after
      the administration of clonidine to assess growth hormone reserve.

PMID- 8299304
TI  - Pediatric care after snakebite: comfort from shared experience.

PMID- 8299305
TI  - Tympanic thermometry: poor correlations.

PMID- 8299306
TI  - An Easter orchidometer.

PMID- 8299307
TI  - Is cocaine a risk factor to necrotizing enterocolitis?

PMID- 8299308
TI  - Status epilepticus encephalopathy with cat-scratch disease.

PMID- 8299309
TI  - Legally mandated options available to children with ADHD within public education.

PMID- 8299310
TI  - Criteria for judging proposals for national health care reform with respect to
      therapeutics.

PMID- 8299311
TI  - Debrisoquin oxidation genotype and susceptibility to lung cancer.
AB  - The association between the polymorphism of the cytochrome P450 debrisoquin
      hydroxylase (CYP2D6) and lung cancer is controversial. Previous reports suggested
      a link between CYP2D6 phenotype and lung cancer, with poor metabolizers having
      reduced susceptibility. Nevertheless, negative findings have also been published.
      By using allele-specific amplification, we have studied the frequency of four
      CYP2D6 (wild type and mutant) alleles in 89 patients with histologically proved
      bronchogenic carcinoma and in 98 healthy volunteers. Our findings confirm that
      poor metabolizers are underpresented among patients with lung cancer because of a
      different genetic background. Our findings also reveal that the rare CYP2D6(C)
      mutant allele is sixfold more frequent among patients with lung cancer (p <
      0.0005). This suggests that the CYP2D6(C) allele could be considered as an
      additional risk factor because carriers could have higher susceptibility to the
      development of lung cancer.

PMID- 8299312
TI  - Thiopurine methyltransferase activity in American white subjects and black
      subjects.
AB  - BACKGROUND: Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that
      preferentially catalyzes the S-methylation of aromatic and heterocyclic
      sulfhydryl compounds, including 6-mercaptopurine. TPMT exhibits genetic
      polymorphism in white populations, with 89% of individuals having high TPMT
      activity, 11% having intermediate activity, and one in 300 having extremely low
      or absent activity. TPMT activity is inversely correlated with formation of
      active 6-mercaptopurine metabolites (thioguanine nucleotides), thereby
      influencing 6-mercaptopurine toxicity and efficacy. METHODS: To investigate
      ethnic and gender differences in TPMT, we measured erythrocyte TPMT activity in
      209 white healthy subjects and 196 black healthy subjects (202 women and 303
      men). RESULTS: The black population had lower TPMT activity than the white
      population (median, 14.4 versus 16.8 units/ml packed erythrocytes; p < 0.001).
      Maximum likelihood estimation of TPMT activity distribution identified 91.9% and
      93.9% with high activity and 7.7% and 6.1% with intermediate activity in the
      white and black groups, respectively. CONCLUSIONS: These data indicate that TPMT
      activity is similarly polymorphic in American black subjects and white subjects,
      although median TPMT activity is approximately 17% lower in black subjects.

PMID- 8299313
TI  - Enhanced covalent binding of tolmetin to proteins in humans after multiple
      dosing.
AB  - The in vivo stability of tolmetin-plasma protein adducts was characterized in six
      healthy human volunteers after a 400 mg single dose and after a multiple-dose
      regimen of 400 mg tolmetin every 12 hours for 10 days. Although the mean +/- SD
      maximum bound concentration was only 2.72 +/- 0.98 ng drug/mg protein after a
      single dose, it was almost an order of magnitude higher after multiple dosing.
      The protein adduct exhibited an average half-life of 4.8 +/- 0.9 days in contrast
      to the much shorter 5-hour half-lives for tolmetin and its glucuronide.

PMID- 8299314
TI  - Dispositional factors do not contribute to the enantiospecificity of the
      cardiovascular effects of phenylpropanolamine.
AB  - The pharmacokinetics and blood pressure response of the phenylpropanolamine
      enantiomers (i.e., d- and l-phenylpropanolamine) were determined after the
      separate oral administration of racemic dl-phenylpropanolamine (75 mg), l
      phenylpropanolamine (37.5 mg), and d-phenylpropanolamine (37.5 mg) to six healthy
      volunteers. No significant differences were observed between any of the
      pharmacokinetic parameters of d- and l-phenylpropanolamine when the enantiomers
      were administered individually or as the racemate. There was also no difference
      in the ex vivo plasma protein binding of d- and l-phenylpropanolamine, determined
      individually or as the racemate. Significant increases from baseline in systolic
      and diastolic blood pressure (supine and standing) were observed for dl- and l
      phenylpropanolamine, whereas d-phenylpropanolamine had no effect on blood
      pressure. The effects of dl- and l-phenylpropanolamine on blood pressure were not
      significantly different. The data from this study show that pharmacokinetic
      factors do not contribute to the stereospecificity of the cardiovascular effects
      of phenylpropanolamine or to the interindividual variability in the blood
      pressure response to phenylpropanolamine.

PMID- 8299315
TI  - Verapamil decreases lymphocyte protein kinase C activity in humans.
AB  - To determine if clinically used doses of the calcium antagonist verapamil
      measurably alter intracellular transduction mechanisms associated with the
      phosphatidylinositol pathway, lymphocyte protein kinase C activity was determined
      in subjects in a drug-free state, after 1 week of verapamil treatment (120 mg
      three times daily) and after a second week of verapamil treatment (240 mg
      sustained-release preparation once daily). Nine healthy male volunteers were
      studied and in these subjects baseline protein kinase C activity (mean +/- SEM;
      5.07 +/- 0.76 pmol/microgram protein/min) tended to decrease after 1 week (3.50
      +/- 0.20 pmol/micrograms protein/min) and was significantly decreased after 2
      weeks (3.14 +/- 0.27 pmol/micrograms protein/min; p < 0.05 from baseline) of
      verapamil treatment. These data indicate that verapamil, at usual clinical doses,
      decreases protein kinase C activity in a marker tissue, the circulating
      lymphocyte. If protein kinase C activity in this tissue is a surrogate for other
      verapamil target tissues, such as vascular smooth muscle and heart muscle, these
      findings may provide insight into the in vivo mechanism by which verapamil
      decreases protein synthesis, limits cell growth, and reverses cellular
      hypertrophy in these tissues.

PMID- 8299316
TI  - Dietary fatty acids are also drugs.

PMID- 8299317
TI  - Pharmacodynamics of MK-0963, a new 5 alpha-reductase inhibitor: effects on serum
      androgen concentrations.
AB  - The hormonal effects after a 10-day administration of a 4-azasteroid inhibitor of
      5 alpha-reductase, MK-0963 (previously L-654,066), were evaluated in 35 healthy
      male volunteers in an increasing-dose, five-panel design. Marked suppression of
      serum dihydrotestosterone was observed after the once-daily administration at
      each active dose level (placebo, 0.1, 0.5, 1.0, 10, and 25 mg). Maximum
      dihydrotestosterone suppression occurred at doses greater than or equal to 10 mg.
      The mean percentage (+/- SE) decreases in dihydrotestosterone at 24 hours after
      the last dose in the groups treated with the 10 and 25 mg doses were 78% +/- 4.9%
      and 80% +/- 2.9%, respectively. The 25 mg dose maintained a dihydrotestosterone
      suppression of at least 70% for more than 6 days after the last dose. No
      consistent changes in serum testosterone were noted. This study shows that
      administration of multiple doses of MK-0963 results in a substantial suppression
      of serum dihydrotestosterone with no consistent influence on serum testosterone
      concentrations.

PMID- 8299318
TI  - Pharmacokinetics and pharmacodynamics of a new cardiotonic vasodilator agent,
      349U85, in normal subjects.
AB  - OBJECTIVE: To assess the pharmacodynamics and pharmacokinetics of single oral
      doses of a new vasodilator-cardiotonic agent, 349U85 hydrochloride [6-piperidino
      2(1H)-quinolinone hydrochloride], in healthy male subjects. METHODS: This
      randomized, parallel, double-blind, placebo-controlled, dose escalation trial was
      conducted at a university-based clinical research center among 27 healthy male
      subjects. Data measurements used in the study included cardiac index, supine and
      standing blood pressure, 24-hour ambulatory electrocardiography, and 12-lead
      electrocardiography. RESULTS: Doses from 2 mg to 250 mg were well tolerated.
      Cardiac index, supine heart rate, and orthostatic hypotension, indicators of
      inotropic, chronotropic, and vasodilator effects, respectively, correlated to
      plasma concentrations of 349U85 and of its metabolite, 661U88. Results suggest
      that 349U85 may be more responsible for inotropic effects, whereas 661U88 may be
      more responsible for vasodilatory and chronotropic effects. These results are
      consistent with the preclinical pharmacologic profile for these two compounds.
      Headache, orthostatic dizziness, and hypotension tended to occur more frequently
      at higher doses and were temporally related to drug administration.
      Pharmacokinetic analyses indicate nonlinearity of 349U85 and 661U88, suggestive
      of saturation of metabolism and large interindividual variability in maximum
      plasma drug concentration and area under the plasma concentration-time curve. The
      source of the variability is not known. The time to maximum distribution was
      approximately 0.7 hours for both 349U85 and 661U88; the terminal elimination half
      life was 1 hour for 349U85 and 3 hours for 661U88. Holter monitoring revealed
      asymptomatic increases in ventricular and supraventricular ectopic activity in
      some volunteers; ectopy appeared to be related to the dose of 349U85 and
      generally occurred at higher doses.

PMID- 8299319
TI  - A placebo-controlled study of three clonidine doses for smoking cessation.
AB  - BACKGROUND AND OBJECTIVE: Clonidine in doses of 150 to 450 micrograms per day has
      been reported to reduce symptoms of craving associated with tobacco withdrawal
      and, in some cases, to improve long-term abstinence rates of smoking cessation
      programs. However, subjects frequently experienced symptoms of dry mouth and
      drowsiness. This study investigated the lower end of the effective dose range of
      clonidine for smoking cessation to identify the lowest useful dose and thus
      minimize the adverse effects of the drug. METHODS: A randomized, double-blind,
      four-way crossover design compared the effects of clonidine doses or placebo
      within individual subjects for 4 consecutive weeks. Smokers who were highly
      nicotine dependent were randomly assigned to different sequences of placebo and
      300, 200, and 100 micrograms clonidine per day. Subjects were treated for 4 days
      of each treatment week and began smoking cessation from the end of day 2. Smokers
      recorded withdrawal symptoms on multiple visual analog scales during days 3 and 4
      before resuming normal smoking until the next period of smoking cessation.
      RESULTS: A statistically significant dose-response effect was found for craving
      scores (dose-response gradient, -3.8/100 micrograms; 95% confidence interval
      [CI], -6.2 to -1.5; p = 0.002) but not for pooled tobacco withdrawal scores. The
      dose of 300 micrograms per day reduced mean craving scores significantly (-16%;
      95% CI, -31% to -1%). Dosing with 200 micrograms approached statistical
      significance (-14%; 95% CI -30% to 1%) but dosing with 100 micrograms did not (
      6%; 95% CI, -22% to 9%). Troublesome adverse experiences were reported by more
      than 67% of subjects during 200 and 300 micrograms dosing. CONCLUSIONS: This
      study showed a statistically significant dose-response effect of clonidine on
      tobacco withdrawal craving and a reduction in mean craving scores of 16% during
      300 micrograms dosing. However, its clinical usefulness is doubtful because of
      frequently reported adverse experiences.

PMID- 8299320
TI  - Urinary iron excretion depends on the mode of administration of the oral iron
      chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with homozygous beta
      thalassemia.
AB  - OBJECTIVE: To examine the effect of frequency of oral administration of 1,2
      dimethyl-3-hydroxypyrid-4-one (L1) on urinary iron excretion. HYPOTHESIS:
      Sustained serum concentrations of L1 will cause more iron chelation than the same
      daily dose given in larger but less frequent amounts. PATIENTS AND METHODS: Ten
      patients with thalassemia with a mean age of 20.9 +/- 4.7 years (range, 13 to 27
      years), who were receiving regular treatment with 75 to 100 mg/kg/day oral L1,
      received 75 mg/kg/day L1 orally in equally divided doses: every 6 hours for 3
      days and every 12 hours for 3 days. The two study periods occurred 1 month apart
      immediately after the monthly blood transfusions. Urine was collected for two
      consecutive 24-hour periods during each of the different schedules. Serial blood
      samples were collected from six patients over a 6-hour period and analyzed for
      total L1 and the L1 glucuronide metabolite concentrations. RESULTS: The patient's
      mean hemoglobin levels (138.8 +/- 12.5 and 139.0 +/- 11.6 gm/L) and ferritin
      levels (2856.4 +/- 2207.8 and 2890.0 +/- 2264.4 micrograms/L) were similar during
      the every-6-hour and every-12-hour L1 administrations, respectively. There was
      significantly more urinary iron excretion when L1 was administered every 6 hours
      (0.59 +/- 0.29 mg/kg/day) versus every 12 hours (0.40 +/- 0.26 mg/kg/day; p =
      0.0129). Calculated 24-hour area under the plasma concentration-time curve of L1
      was similar during the every-6-hour (7023.9 +/- 2637.8 mg.min/L) and every-12
      hour (7050.1 +/- 1668.8 mg.min/L) experiments. CONCLUSIONS: These data suggest
      that the sustained presence of L1 in the blood results in greater chelation of
      iron than that observed with larger, less frequent doses.

PMID- 8299321
TI  - Nicotine metabolism in cigarette smokers and nonsmokers.

PMID- 8299322
TI  - Pharmacodynamic modeling of nonsteroidal anti-inflammatory drugs: antipyretic
      effect of ibuprofen.

PMID- 8299323
TI  - USAN Council. List No. 357. New names. Alvircept sudotox.

PMID- 8299324
TI  - USAN Council. List No. 357. New names. Corticorelin ovine triflutate.

PMID- 8299325
TI  - Crookshank lecture: risks from radiation--perception and reality.

PMID- 8299326
TI  - Measurement of tissue-bound amiodarone and its metabolites by computed
      tomography.
AB  - Amiodarone is strongly tissue-bound and serum levels are a poor guide to
      therapeutic efficacy. The electrocardiographic measure of the QT interval
      corrected for heart rate (QTc) is a better guide but is unhelpful in patients
      with bundle branch block or U-waves on the electrocardiogram. Myocardial
      amiodarone levels are the most accurate guide but are not easy to obtain. There
      is, however, a relationship between myocardial concentration and hepatic
      concentration of amiodarone and its metabolites. Since amiodarone contains
      iodine, and there is hepatic uptake, the increased hepatic attenuation from
      single slice computed tomography was compared with serum levels and the
      electrocardiographic QTc in 12 patients before and during amiodarone therapy.
      Hepatic attenuation increased by a mean value of 18.25 HU over a 12 month study
      period. This increase correlated well with increased QTc (r = 0.83) and with
      serum amiodarone levels (r = 0.89), but less well with serum desethyl amiodarone
      levels (r = 0.43). An iodine-containing phantom was used to construct a curve of
      attenuation against iodine concentration in mol/l. Thus an indirect measurement
      of amiodarone concentration in g/l wet weight of liver could be determined.

PMID- 8299327
TI  - The value of computed tomographic measurements in osteosarcoma as a predictor of
      response to adjuvant chemotherapy.
AB  - The response to pre-operative adjuvant chemotherapy was assessed with computed
      tomography (CT) in 41 osteosarcomas of the long bones of the lower limb.
      Measurements were made of cross-sectional tumour areas and volumes on both the
      pre- and post-chemotherapy CT examinations. Changes in these measurements were
      compared with the percentage necrosis determined from examination of the tumour
      histology from the excised specimen in 39 cases. An increase in the relative size
      of the tumour (expressed as a ratio of the pretreatment volume) showed a
      statistically significant correlation with a poor tumour response as judged by
      the degree of tumour necrosis. Further analysis of the results showed that
      quantitative assessment of tumour response by CT is able to identify cases with
      poor response to therapy (negative predictive value = 0.9). This is, however,
      only achieved with a low specificity (0.5-0.6). These findings are in agreement
      with other studies of tumour volume changes using MR imaging.

PMID- 8299328
TI  - Sonographic findings in gastrointestinal and peritoneal tuberculosis.
AB  - The various ultrasound (US) findings in 90 patients with abdominal
      (gastrointestinal, peritoneal, mesenteric and lymph node) tuberculosis (TB)
      studied in an area of high incidence of TB over a 1 year period were analysed.
      The lesions encountered were intestinal (n = 31), extraintestinal (n = 39), or a
      combination (n = 20). The extraintestinal lesions included free and loculated
      ascites (n = 36), localized ascites ('Club Sandwich sign') (n = 4), adhesions (n
      = 14), peritoneal thickening (n = 14), peritoneal nodules (n = 3),
      lymphadenopathy (n = 23) and cold abscesses (n = 10)-of these, the presence of
      fine fibrinous strands in the ascetic fluid, localized ascites and caseous or
      calcified lymph nodes were highly suspicious of a diagnosis of TB in appropriate
      clinical settings. The bowel lesions were characterized by concentric bowel wall
      thickening (n = 31) with ulceration in six. Bowel thickening, when present in the
      ileocaecal junction and especially when situated in the subhepatic position, was
      suggestive of a tuberculous etiology. Complex masses in the abdomen pointed to an
      advanced stage of the disease. US is a useful imaging modality in patients
      clinically suspected of having abdominal TB for diagnosis and follow-up, although
      in a few cases differentiation of it from metastatic disease is difficult. When
      bowel involvement is suspected, barium studies should be performed.

PMID- 8299329
TI  - Pneumatic reduction of intussusception: clinical experience and factors affecting
      outcome.
AB  - Between 1987 and 1992, 54 patients (32 male, 22 female) underwent 62 attempts at
      pneumatic reduction of intussusception. The mean age at presentation was 12.5
      months (range 2.5 to 4 years 4 months). A retrospective review of all cases was
      performed to identify success rate and factors affecting it. Successful reduction
      was achieved in 46 cases (74%). One case was complicated by perforation and four
      cases (7%) by early recurrence. Patients with failed pneumatic reduction were
      more likely than those with successful reduction to have: (1) long duration of
      symptoms; (2) bleeding per rectum; (3) small bowel obstruction. Among the 16
      cases of failed reduction, surgical findings were: five cases of ileo-ileo-colic
      intussusception, one with ileo-ileal, one with perforated ischaemic colon during
      air enema and one whose intussusception was found to be reduced at surgery. Three
      patients had lead points: Meckel's diverticula in two and a pinworm in one.
      Resection was required in three cases for non-viable bowel and in another two for
      the Meckel's diverticula. Pneumatic reduction of intussusception offers a high
      success rate with few complications. Performing an air enema earlier in the
      course of the disease may increase the chance of successful reduction.

PMID- 8299330
TI  - Colonic preparation with Picolax: patient tolerance and approaches to fluid
      replacement.
AB  - Sodium picosulphate (Picolax) is widely used for bowel preparation prior to
      colonic investigation or surgery. The most troublesome side effect reported is
      headache, which has been thought to be due to dehydration. In a prospective
      randomized study we investigated the incidence of adverse effects in patients
      given Picolax prior to barium enema examination, and assessed the incidence of
      adverse effects with different oral fluid regimens. A total of 197 outpatients
      were allocated to one of five fluid regimens on the day prior to the enema: (a) 4
      pints of Dioralyte (glucose and electrolyte solution); (b) 4 pints of half
      strength Dioralyte; (c) 4 pints of water; (d) 6 pints of water; and (e) free
      fluids. In a questionnaire, 36% of patients had no headache (graded 0/5), while
      38% had a significant headache (graded 3/5 or greater). Sixteen per cent had
      significant abdominal pain, 42% had dry mouths, 43% thirst and 34% tiredness or
      irritability. There was no correlation between headache and fluid regimen.
      Furthermore, we have found no evidence of dehydration. None of the five fluid
      regimens was shown to offer any advantage, and we therefore recommend that
      patients be allowed to drink according to thirst when taking Picolax.

PMID- 8299331
TI  - What is the value of measuring renal parenchymal thickness before renal biopsy?
AB  - Reduced renal length is widely used to diagnose chronicity in patients with renal
      impairment. A length of 9 cm or less measured ultrasonographically is considered
      to indicate irreversible disease. However, some patients with normal renal length
      have thin parenchyma. The aim of this study was to determine the relationship
      between ultrasonographically measured parenchymal thickness and renal length and
      to correlate parenchymal thickness with the histology obtained at renal biopsy.
      Sixty-four patients, aged 16-74 years, who had had a renal biopsy were evaluated
      retrospectively. Histology was considered in five categories: I, interstitial
      nephritis (n = 13); II, glomerulonephritis (28); III, diabetes
      mellitus/metabolic/other (8); IV, chronic renal disease (CRD) (11); V,
      hypertension/vascular disease (4). There was a good linear correlation between
      renal length and renal parenchymal thickness (r = 0.64, P < 0.001). Both were
      reduced most in patients with CRD. Sixty-four per cent of patients with CRD had
      renal parenchymal thickness 1.5 cm or less, compared to 38% in group I, 25% in
      groups II and V, and 7% in group II. Although 11/37 (30%) of patients whose serum
      creatinine had increased 3 months post-biopsy had parenchymal thickness 1.5 cm or
      less, so did 6/27 (23%) whose creatinine decreased. Like renal length,
      parenchymal thickness gives an indication of the chronicity of renal failure.
      However, some patients with parenchymal thickness 1.5 cm or less still have
      potential for improvement. This measurement alone should not be used to obviate
      renal biopsy.

PMID- 8299332
TI  - Unilateral increase in mammographic density with hormone replacement therapy.
AB  - Two cases of localized unilateral increase in mammographic density are described
      in women who had commenced hormone replacement therapy (HRT) just before or
      within several weeks of their first normal screening mammogram. The increase in
      density at a subsequent screen required recall to an assessment clinic to exclude
      cancer in the affected breast. The relationship of HRT to mammographic density is
      discussed.

PMID- 8299333
TI  - Assessment of the role of ultrasound in the differentiation of radial scars and
      stellate carcinomas of the breast.
AB  - Radial scars are benign lesions of the breast which cannot be reliably
      distinguished from carcinoma by their mammographic appearances alone [1,2]. The
      present wisdom is that all such lesions should be biopsied [2]. We report a
      retrospective study carried out to assess whether there are any ultrasound
      imaging features that may be useful in differentiating radial scars from
      carcinoma and so reduce the need for excision biopsy. Over a period of 44 months
      between 1988 and 1992, 530 patients underwent surgery for abnormalities detected
      by routine mammographic screening. Of the 191 benign lesions excised, 24 were
      radial scars. Ultrasound images of 21 radial scars were mixed with an equal
      number of images of histologically proven carcinomas that had similar
      mammographic appearances. These images were reviewed 'blind' by a single
      radiologist. We were unable to find any ultrasound appearances sufficiently
      specific to radial scars to allow confident exclusion of malignancy. We therefore
      endorse the current practice of biopsying all mammographically detected stellate
      lesions.

PMID- 8299334
TI  - Chest radiography guidelines for general practitioners: a practical approach.
AB  - An intensive programme of guideline development and dissemination is not always
      practical. We designed general practitioner guidelines for chest radiography and
      disseminated them to a group of 33 practices selected randomly from the practices
      that refer more than five patients for chest radiography annually. The subsequent
      2500 requests were analysed and demographic data, the referring practice and the
      relevant history noted. We documented a reduction in the proportion of referrals
      that were contrary to the guidelines by 30.5% (from 8.2% to 5.7%, P = 0.016), a
      reduction in referral rate with an inadequate history by 29.7% (from 15.5% to
      10.9%, P = 0.0008) and an increase in the frequency that a presumptive diagnosis
      was stated by 14.5% (from 42.9% to 49.1%, P = 0.0025). There was no overall
      reduction in referral rate in the study group and the reasons for this are
      discussed. We conclude that guidelines for chest radiography are effective in
      reducing inappropriate requests and can also improve the clinical information
      provided.

PMID- 8299335
TI  - The risk of blood splash contamination during angiography.
AB  - Blood splash contamination of the conjunctivae or buccal mucosa may occur during
      angiography and angioplasty. Since there is a risk of contracting Hepatitis B or
      HIV via this route, staff should be aware of this potential source of infection.
      The use of protective masks and goggles or glasses should be considered. We have
      studied the risk of contamination by asking both the radiologist and angiography
      nurse to wear spectacles and disposable masks during 100 consecutive angiographic
      procedures. The number of splashes was counted at the end of each procedure.
      Blood splashes occurred in seven procedures and there was a total of 23 splashes
      during the study. In conclusion, we believe that there is a significant risk of
      conjunctival or mucosal contamination with blood during angiographic procedures
      and given the potential seriousness of transmission of Hepatitis B or HIV,
      radiologists and nursing staff must be aware of this risk.

PMID- 8299336
TI  - Case report: magnetic resonance demonstration of haemorrhagic acoustic neuroma.
AB  - A 70-year-old patient with a history suggestive of acoustic neuroma developed
      sudden neurological symptoms. CT showed an enhancing mass in the left cerebello
      pontine angle thought to be a meningioma. Magnetic resonance (MR) with gadolinium
      enhancement demonstrated appearances consistent with a haemorrhagic acoustic
      neuroma, a diagnosis confirmed at surgery. The literature regarding haemorrhagic
      intracerebral tumours and MR appearances of acoustic neuroma is reviewed.

PMID- 8299337
TI  - Case report: asymptomatic aneurysmal intrahepatic porto-hepatic venous shunt-
      diagnosis by ultrasound.
AB  - Intrahepatic porto-hepatic venous shunts are rare entities with less than 20
      cases reported in the literature. Many are associated with liver cirrhosis, but
      some appear to be of developmental origin. The rarest type of such a shunt is one
      via a portal vein aneurysm. A case is reported where the diagnosis was made by
      colour duplex ultrasound. No further investigation or treatment was deemed
      necessary. The ability to make such a diagnosis without the many invasive
      procedures hitherto employed indicates the value of this modality in the
      investigation of vascular anomalies.

PMID- 8299338
TI  - Case report: progressive multifocal leukoencephalopathy with prominent medullary
      veins on angiogram.
AB  - A case of progressive multifocal leukoencephalopathy associated with systemic
      lupus erythematosus is presented. Angiography revealed early filling of prominent
      medullary veins in the region of the lesion, suggesting active demyelination.

PMID- 8299339
TI  - Case report: transrectal ultrasound in the diagnosis of ano-rectal varices.
AB  - Extensive ano-rectal varices were diagnosed by transrectal ultrasound (TRUS) in a
      patient with portal hypertension who presented with an altered bowel habit. The
      diagnosis of ano-rectal varices is usually made by direct inspection during
      procto-sigmoidoscopy in patients who present with rectal bleeding. However, the
      sigmoidoscopic and barium enema appearances of varices may mimic that of a
      tumour. A firm diagnosis can readily be made using TRUS and the local extent of
      varices clearly mapped out.

PMID- 8299340
TI  - Magnetic resonance imaging of fistula-in-ano: technique, interpretation and
      accuracy.
AB  - The aim of this study was to document the appearances of fistula-in-ano on
      magnetic resonance imaging (MRI) and to prospectively evaluate the accuracy of
      MRI in the pre-operative assessment of anal fistulae. Patients with a clinical
      diagnosis of fistula-in-ano and awaiting surgery (n = 35) were examined with MRI.
      The fistulous tracks with their secondary extensions and abscesses are readily
      seen as low signal on T1-weighted images and high signal areas on STIR images. In
      order to determine the accuracy of the MRI interpretations, an experienced
      coloproctologist operated on all 35 patients without the knowledge of the scan
      interpretations and the findings at surgery were compared with the MRI scan
      interpretations. Concordance rates between MRI and operative findings were 86%
      for presence and course of the primary track, 91% for the presence and site of
      secondary extensions or abscesses and 97% for the presence of horse-shoeing.
      Although operative findings by an experienced coloproctologist were taken as the
      gold standard, we have shown that in 9% of our study group, failure of healing
      was related to pathology missed at surgery which had been documented on pre
      operative MRI. It is probable, therefore, that the accuracy of MRI is higher than
      the figures quoted above. MRI is advocated as the imaging method of choice in the
      assessment of anal fistulae and its use may lead to a reduction in the recurrence
      rate due to inaccurate surgical assessment.

PMID- 8299341
TI  - Enlargement of the pterygo-masseteric muscle complex.

PMID- 8299342
TI  - Lung cancer.

PMID- 8299343
TI  - Esterases in quail (Coturnix coturnix). Physicochemical and developmental
      aspects.
AB  - 1. Soluble esterases of digestive system organs of various developmental stages
      in the quail (Coturnix coturnix) were resolved by polyacrylamide gel
      electrophoresis into several molecular forms which were characterized as
      carboxylesterases, acetylesterases, cholinesterases and esterases sensitive to
      eserine. 2. The pI of the majority of esterasic activity in several quail and
      chicken tissues was observed in the range of 5.1-5.6, while the apparent
      molecular weight in liver extracts was 60,000. 3. The expression of the esterase
      multiple molecular forms was found to be both tissue- and developmental stage
      specific, with electrophoretic patterns becoming more complex in number and/or
      staining intensity upon hatching and thereafter, especially in liver and
      intestine.

PMID- 8299344
TI  - L-glutamate dehydrogenases: distribution, properties and mechanism.

PMID- 8299345
TI  - Different ouabain sensitivities of Na+/K(+)-ATPase from Poekilocerus bufonius
      tissues and a possible physiological cost.
AB  - 1. The properties of Na+/K(+)-transporting ATPase in microsomal preparation from
      mid-gut of the grasshopper, Poekilocerus bufonius, were investigated and compared
      with the same enzyme from brain and excretory system. 2. Two components of
      ATPases activity are present in the three tissues studied. 3. The physiochemical
      properties of Na+/K(+)-transporting ATPase from mid-gut, brain and excretory
      system (hind-gut plus Malpighian tubules) are essentially the same. 4. The
      calculated values of PI50 were 2 (I50 = 1 x 10(-2) M), 3.7 (I50 = 2 x 10(-4) M)
      and 6.4 (I50 = 3.98 x 10(-7)) for Na+/K(+)-ATPase from mid-gut, excretory system
      and brain, respectively. The mid-gut contains the most ouabain-resistant Na+/K(+)
      ATPase. 5. The results suggest that P. bufonius have developed some tolerance to
      toxic cardiac glycosides (CGS), but there is a possibility of autotoxicity as
      indicated by the presence of ouabain-sensitive ATPase from brain tissue. 6. It
      was concluded that the dissimilarities of Na+/K(+)-ATPases from different tissues
      of P. bufonius are probably due to tissue-dependent differences in ouabain
      sensitivity (or isoenzymes pattern) available in the same insect. 7. The atrophy
      of female flight muscle of P. bufonius suggests the possibility of physiological
      cost inflicted on insects consuming poisonous plants.

PMID- 8299346
TI  - Comparison of the intravascular metabolism of cholesteryl esters and apoproteins
      of plasma low- and high-density lipoproteins in the rat (Rattus norvegicus), an
      animal species without plasma cholesteryl ester transfer activity.
AB  - 1. The intravascular metabolism of the cholesteryl esters (CE) and apoproteins of
      low density lipoproteins (LDL) and high density lipoproteins (HDL) was compared
      in the rat, an animal species without plasma cholesteryl ester transfer activity
      (CETA). 2. The apoproteins and the CE of LDL had identical catabolic rates, and
      there was no transfer of LDL CE to other lipoprotein classes. 3. The CE of the
      HDL, however, had higher catabolic rates than the apoproteins, and there was
      transfer of HDL CE to LDL but not to very low density lipoproteins.

PMID- 8299347
TI  - Cholesterol metabolism in New World primates: comparative studies in two tamarin
      species (Saguinus oedipus and Saguinus fuscicollis) and the squirrel monkey
      (Saimiri sciureus).
AB  - 1. Cholesterol metabolism has been characterized in three species of New World
      primates, the cotton-top tamarin, the saddle-back tamarin, and the squirrel
      monkey. 2. When fed a diet containing cholesterol, the three species exhibited
      differing responses of plasma cholesterol levels. 3. Dietary cholesterol
      absorption was determined and plasma cholesterol die-away kinetics were analyzed
      in terms of a two-pool model. 4. The results of the analyses of cholesterol
      turnover are consistent with the observed species-specific differences in plasma
      cholesterol values and cholesterol absorption. 5. Cholesterol metabolism differs
      between the two tamarin species, as well as between the tamarins and the squirrel
      monkey. 6. Implications of species-specific differences between tamarin species
      are discussed in terms of the use of tamarin species as animal models for
      comparative studies of cholesterol metabolism and the etiology of cancer and
      cardiovascular disease.

PMID- 8299348
TI  - Feline and canine milk lysozymes.
AB  - 1. The electrophoretic characteristics of feline (Felis catus) and canine (Canis
      familiaris) milk lysozymes were studied using starch gel electrophoresis and
      isoelectric focusing. 2. Feline milk lysozyme was found to be polymorphic (two
      variants, designated A and B with frequencies of 0.13 and 0.87, respectively).
      Canine milk lysozyme was not polymorphic. 3. The lytic activities of feline and
      canine milk lysozymes were examined in buffers of varying pH and ionic strength.
      Preliminary kinetics studies were done. 4. Maximal lytic activity for both
      lysozymes was found in imidazole-HCl buffer pH 7.4 and both exhibited second
      order reaction kinetics. 5. Amino acid compositions of both lysozymes were
      determined.

PMID- 8299349
TI  - Heat-shock response in camel (Camelus dromedarius) blood cells and adaptation to
      hyperthermia.
AB  - 1. We demonstrate the difference between the reactions of camel (Camelus
      dromedarius) lymphocytes and erythrocytes to heat-shock treatment. 2. Lymphocytes
      of this organism characteristically have a higher resistance of general protein
      synthesis to elevated temperature in comparison with human lymphocytes. 3. Camel
      lymphocytes exhibited strong induction of constitutively expressed 73 kDa heat
      shock protein (hsp 73) after heat-shock but failed to synthesize an inducible
      member of the same family (hsp 72) at high temperatures. 4. Nucleated camel
      erythrocytes do not synthesize any heat-shock proteins after temperature
      elevation. 5. Western blot analysis, using polyclonal antibody for hsp 73,
      revealed high levels of this protein in camel lymphocytes and diminished, but
      significant, amounts of hsp 73 protein in the erythrocytes under normal
      physiological conditions. 6. The role of 73 kDa hsp in providing thermotolerance
      of camel blood cells is discussed.

PMID- 8299350
TI  - Rabbit pancreatic polypeptide.
AB  - 1. In almost all studies involving localization or quantitation of regulatory
      peptides, an essential prerequisite is the generation of specific antisera in
      rabbits. Despite this almost universal practice, the primary structures of some
      established regulatory peptides, such as pancreatic polypeptide (PP), of the
      rabbit, remain unknown. 2. Here we report the full primary structure of PP
      isolated from extracts of rabbit pancreas. 3. PP immunoreactivity was purified
      using an antiserum (PP 221) generated to the highly-conserved C-terminal
      hexapeptide amide of mammalian PP. A single molecular form of rabbit PP was
      consistently resolved during sequential chromatographic fractionations. 4.
      Automated Edman degradation established the full primary structure as:
      APPEPVYPGDDATPEQMAEYVADLRRYINMLTRPRY. The molecular mass derived from this
      sequence (4196.7 Da), was in full agreement with that determined by mass
      spectroscopy (4196 Da). The peptide was deemed to be C-terminally amidated due to
      its full molar crossreactivity with the amide-requiring PP antiserum employed. 5.
      When compared with all other known mammalian PP sequences, rabbit PP displays
      three unique substituted sites, Pro at position 3, Glu at position 19 and Val at
      position 21.

PMID- 8299351
TI  - An analysis of pH tolerance and substrate preference of isolated skeletal muscle
      mitochondria from Bufo marinus and Rana catesbeiana.
AB  - 1. The effects of varying pH and substrate on isolated skeletal muscle
      mitochondria from Bufo marinus and Rana catesbeiana were investigated. 2. For
      both species, VO2 max significantly decreased at all pH < 7.3 (P < 0.05), while
      maximum values were observed at a pH range of 7.3-7.6 with B. marinus maintaining
      a greater VO2 max than R. catesbeiana. 3. Respiratory control values (RCR)
      decreased significantly at all pH < 6.9 for both species (P < 0.05). 4. Isolated
      mitochondria from both species were maintained at pH = 7.2 and O2 consumption
      measured under five separate substrate conditions. 5. A rank preference was
      established based upon state 3 and RCR values. 6. Substrate preference was
      identical for both species and interspecific comparisons revealed differences in
      state 3 respiration and coupling.

PMID- 8299352
TI  - Characteristics of phospholipase C present in membranes of Xenopus laevis
      oocytes. Stimulation by phosphatidic acid.
AB  - 1. Phospholipase C activity present in the membranes of Xenopus laevis oocytes
      has been studied. 2. These membranes contain an activity capable of hydrolyzing
      phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol
      4,5-bisphosphate. 3. Hydrolysis of PtdIns 4,5-P2 is absolutely dependent on the
      presence of Ca2+, however, the hydrolysis of PtdIns occurs in the absence of Ca2+
      but addition of the cation stimulates the reaction. 4. Spermine, spermidine and
      polylysine cause significant stimulation of the phospholipase C activity. 5.
      Phosphatidic acid causes approximately a 2-fold stimulation of the hydrolysis of
      both PtdIns and PtdIns 4,5-P2. With PtdIns as substrate, this stimulatory effect
      of phosphatidic acid is specific and reaches a maximum at a 400 microM
      concentration.

PMID- 8299353
TI  - Comparative studies of phosvitin from chicken and salmon egg yolk.
AB  - 1. A method developed for the isolation of phosvitin from chicken egg yolk was
      successfully applied to the isolation of phosvitin from salmon eggs. 2. Salmon
      roe phosvitin is smaller in molecular size than chicken egg phosvitin. 3.
      Circular dichroism spectra of all phosvitins investigated displayed good
      similarities with spectra showing characteristics of unordered and beta-sheet
      secondary structure. 4. The main component in the Fourier transform infrared
      spectra of chicken egg phosvitin is indicative of unordered conformation, whereas
      the Fourier infrared data of the salmon egg phosvitin are consistent with more of
      beta-sheet structure compared to the chicken egg phosvitin.

PMID- 8299354
TI  - Comparative studies of asparagine-linked sugar chains of immunoglobulin G from
      eleven mammalian species.
AB  - 1. Asparagine-linked sugar chains released by hydrazinolysis from IgGs of
      porcine, equine, bovine, goat, ovine, canine, rabbit, guinea-pig and rat were
      comparatively analyzed by microsequencing and lectin affinity chromatography. 2.
      Sugar chains of all IgGs basically consisted of biantennary complex-type
      oligosaccharides containing 0-2 sialic acid residue(s). More than 70% of the
      oligosaccharides were neutral, except for guinea-pig IgG, and fucosylated
      trimannosyl core structures were dominant except for rabbit IgG. Bisecting N
      acetylglucosamine residue was absent in porcine and equine IgGs. 3. A large
      quantity of galactose-less oligosaccharides were present in IgGs of porcine,
      equine, canine and rat.

PMID- 8299355
TI  - Properties of an arylalkylamine N-acetyltransferase from the nematode, Ascaridia
      galli.
AB  - 1. An arylalkylamine N-acetyltransferase (NAT) of the parasitic nematode,
      Ascaridia galli was studied using either [14C]serotonin (5-HT) or [14C]octopamine
      (OA) as substrates and with acetyl-CoA as the donor of the acetate group. 2. The
      NAT activity towards 5-HT and OA co-eluted from a size-exclusion column and
      appeared to have an M(r) of around 30,000. The enzyme had apparent Km values of
      540 +/- 100 microM (+/- SEM) and 33 +/- 4 microM (+/- SEM) for 5-HT and
      octopamine, respectively, when assayed in the presence of 1 mM acetyl-CoA. 3.
      High levels of NAT were found in the gonads of male and female worms and the
      muscle/body wall. 4. N-acetylation was strongly inhibited by Cu2+ but not by
      other divalent metal ions and the effect of a number of compounds including
      biogenic amines, formamidines, hydrazines, and beta-carbolines on the
      arylalkylamine N-acetyltransferase activity was studied.

PMID- 8299357
TI  - Purification and some properties of low molecular weight crystallins from camel
      lens (Camelus dromedarius).
AB  - 1. The use of an Ultrogel AcA 54 gel-filtration column separates camel lens
      cortex low molecular weight proteins into four peaks containing beta s-, gamma 1
      , gamma 2- and gamma 3-crystallins. 2. The molecular weight of beta s-crystallin
      corresponded to 29 kDa on SDS-PAGE and showed three major bands between pH 5.85
      and 8.45 on isoelectric focusing. In addition, as compared to gamma-crystallins
      it has a lower degree of homology in amino acid composition, a low sulfhydryl
      content and a blocked N-terminal amino acid. 3. gamma 1-, gamma 2- and gamma 3
      crystallins appeared homogenous on SDS-PAGE and their molecular weights were
      recorded as 23, 22 and 21 kDa. The isoelectric points of the gamma-crystallin
      fractions ranged from pH 6.55 to 8.60 and they were found to have an unmodified
      glycine at the N-terminal end. 4. The three camel gamma-crystallin fractions were
      similar in molecular weight, isoelectric points, amino acid composition,
      sulfhydryl concentration and N-terminal amino acid.

PMID- 8299356
TI  - Intraspecific variation in serum proteins of brown hare (Lepus europaeus Pallas,
      1778).
AB  - 1. Serum proteins of brown hare (Lepus europaeus Pallas, 1778) were studied by
      the use of 1D PAGE, 2D agarose-PAGE, immunoblotting, inhibitions of trypsin and
      chymotrypsin, and specific staining for esterase. 2. Some serum proteins were
      identified, and easily interpretable polymorphisms were found in transferrin
      alpha 1B glycoprotein, protease inhibitors ATC2, ATC3 and AT1, esterase ES1 and
      in an unidentified postalbumin PO. 3. On the basis of family studies the evidence
      was obtained that the variants observed in these polymorphic proteins are under
      genetic control by codominant alleles of autosomal loci.

PMID- 8299358
TI  - Purification and properties of the hemoglobins of the platyhelminth Isoparorchis
      hypselobagri (Trematoda: Isoparorchidae) and its host Wallagu attu (catfish).
AB  - 1. The hemoglobins of the trematode Isoparorchis hypselobagri and of its host
      Wallagu attu (catfish) were isolated and purified. 2. SDS-polyacrylamide gel
      electrophoresis showed both to consist of single, 15-17 kDa chains, having
      different electrophoretic mobilities. 3. Isoelectric focusing showed the
      trematode hemoglobin to be homogeneous with a pI of 4.2 and the host hemoglobin
      to consist of several components. 4. Gel filtration of freshly prepared trematode
      hemoglobin revealed one peak corresponding to M(r) approximately 17 kDa; gel
      filtration of a preparation which had been stored for 2-3 months demonstrated the
      presence of two peaks, whose elution volumes corresponded to M(r) of ca 35 and 17
      kDa, respectively. 5. Reversed-phase chromatography of carboxymethylated 35 and
      17 kDa peaks on a C8 column, gave a single peak a and two peaks b and c,
      respectively. 6. Edman degradation of peaks a, b and c obtained provided
      identical sequences of 27 amino acid residues for peaks a and c and another
      sequence differing at 10 of the 27 positions, for peak b. Edman degradation of
      the freshly prepared Isoparorchis hemoglobin provided the first 15 amino acid
      residues found for peaks a and c. The host hemoglobin gave an N-terminal sequence
      completely different from the trematode sequences. 7. Since gel filtration of the
      35 and 17 kDa peaks showed no sign of an interconversion equilibrium, it appears
      that the 35 kDa peak and peak a represent a disulfide-bonded dimer of a monomer
      globin chain which shares the 27 N-terminal residues with chain c, the major
      monomer globin component of the 17 kDa peak.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299359
TI  - Replication of damaged DNA and the molecular mechanism of ultraviolet light
      mutagenesis.
AB  - On UV irradiation of Escherichia coli cells, DNA replication is transiently
      arrested to allow removal of DNA damage by DNA repair mechanisms. This is
      followed by a resumption of DNA replication, a major recovery function whose
      mechanism is poorly understood. During the post-UV irradiation period the SOS
      stress response is induced, giving rise to a multiplicity of phenomena, including
      UV mutagenesis. The prevailing model is that UV mutagenesis occurs by the filling
      in of single-stranded DNA gaps present opposite UV lesions in the irradiated
      chromosome. These gaps can be formed by the activity of DNA replication or repair
      on the damaged DNA. The gap filling involves polymerization through UV lesions
      (also termed bypass synthesis or error-prone repair) by DNA polymerase III. The
      primary source of mutations is the incorporation of incorrect nucleotides
      opposite lesions. UV mutagenesis is a genetically regulated process, and it
      requires the SOS-inducible proteins RecA, UmuD, and UmuC. It may represent a
      minor repair pathway or a genetic program to accelerate evolution of cells under
      environmental stress conditions.

PMID- 8299360
TI  - The physical biochemistry and molecular genetics of sulfate activation.
AB  - This article is an overview of current research in the area of sulfate
      activation. Emphasis is placed on presenting unresolved issues in an appropriate
      context for critical evaluation by the reader. The energetics of sulfate
      activation is reevaluated in light of recent findings that demonstrate that the
      synthesis of activated sulfate is thermodynamically driven by GTP hydrolysis. The
      structural and functional bases of this GTPase activation are discussed in
      detail. The bonding and hydrolysis of the high-energy, phosphoric-sulfuric acid
      anhydride bond of activated sulfate are presented along with an analysis of the
      importance of the divalent cation and pyrophosphate protonation in the equilibria
      governing activated sulfate formation. The molecular genetics of sulfate
      assimilation in prokaryotes is reviewed with an emphasis on the regulation of the
      pathway. Recent discoveries connecting sulfate activation to plant/microbe
      symbiogenesis are presented, as are several examples of the importance of
      activated sulfate in human metabolism and disease.

PMID- 8299361
TI  - Do we need new and different glucocorticoids? A re-appraisal of the various
      congeners and potential alternatives.

PMID- 8299362
TI  - The psoriasis plaque test and topical corticosteroids: evaluation by computerized
      laser profilometry.

PMID- 8299363
TI  - Design of novel soft corticosteroids.

PMID- 8299364
TI  - Topical glucocorticoids and thinning of normal skin as to be assessed by
      ultrasound.

PMID- 8299365
TI  - Side effects of topical glucocorticoids.

PMID- 8299366
TI  - Early detection of glucocorticoid-specific epidermal alterations using skin
      surface microscopy.

PMID- 8299367
TI  - Influence of glucocorticoid substances and the vehicle on skin irritancy:
      determination by profilometry.

PMID- 8299368
TI  - Prednicarbate after different forms of administration. Plasma levels of drug and
      metabolites and effects on endogenous cortisol levels in humans.

PMID- 8299369
TI  - Clinical efficacy of topical glucocorticoid preparations and other types of
      dermatics in inflammatory diseases, particularly in atopic dermatitis.

PMID- 8299370
TI  - Contact allergy to topical glucocorticoids.

PMID- 8299371
TI  - Adverse drug reactions to various topical glucocorticosteroids: quantitative
      aspects.

PMID- 8299372
TI  - Topical glucocorticoids and anti-infectives: a rational combination?

PMID- 8299373
TI  - Topical glucocorticoids: what has been achieved? What is still to be done?

PMID- 8299374
TI  - Glucocorticoid receptors.

PMID- 8299375
TI  - Methods of computer-aided drug design and their applications to steroids.

PMID- 8299376
TI  - Percutaneous absorption of topical corticosteroids.

PMID- 8299377
TI  - Metabolism of topical drugs within the skin, in particular glucocorticoids.

PMID- 8299378
TI  - Influence of glucocorticoids on the epidermal Langerhans cell.

PMID- 8299379
TI  - Effect of glucocorticosteroids on number and function of connective-tissue cells.

PMID- 8299380
TI  - Topical tretinoin prevents corticosteroid-induced atrophy without lessening the
      anti-inflammatory effect.

PMID- 8299381
TI  - Ranking of topical glucocorticoids. Principles and results.

PMID- 8299382
TI  - Suppression of induced inflammation in man.

PMID- 8299383
TI  - A "current contact news" follow-up: controversial subjects and those resulting in
      litigation.

PMID- 8299384
TI  - A dermatologic diary. Portrait of a practice.

PMID- 8299385
TI  - Hand, foot, and mouth disease.

PMID- 8299386
TI  - Hand eczema: the atopic subject and work.
AB  - Of the large number of young persons entering the work force each year, few
      choose their work with more than cursory consideration of their physical ability
      to perform it. This is especially true of atopic persons. When the first
      manifestation of the disease is hand eczema triggered by the first work
      experience, often after the subject has undergone many months of training, the
      answer becomes very difficult. It often requires a job change, with accompanying
      economic and personal loss. When the work is responsible for aggravation or
      activation of the condition, the entire gamut of social services comes into play,
      including medical, legal, rehabilitation, and workers compensation. These lead,
      after months and often years, to job changes that may or may not alleviate or
      ameliorate the condition. For these reasons dermatologists need to have greater
      awareness of the position of the atopic subject in the workplace.

PMID- 8299387
TI  - Allergic contact dermatitis and Langerhans cells: comments on recent
      developments.
AB  - Among the most interesting medical developments of the twentieth century is the
      revelation that the skin is an organ of major immunologic importance (about 95
      percent of resident cells in the epidermis [keratinocytes and Langerhans cells]
      can serve immunologic functions). Allergic contact-type dermatitis and its
      underlying mechanism, allergic contact-type sensitization, have been a highly
      useful model in uncovering the facts that are the basis for this statement. The
      comments in this article deal with a few randomly selected findings that have
      been reported in the literature during the past twenty years. They include the
      probable role of the Birbeck granules in the process of antigen presentation by
      Langerhans cells; photomodulation of important immunologic reactions by
      ultraviolet radiation; a previously unrecognized form of contact allergy,
      apparently present only at clinically active sites of atopic dermatitis (and
      engendered by small protein antigens rather than by small molecular ["simple
      chemical"] compounds); and the first factual evidence that epidermal Langerhans
      cells may be subject to control by intraepidermally located parts of the
      peripheral nervous system.

PMID- 8299388
TI  - Contact leukoderma associated with the use of hair colors.
AB  - Four cases of contact leukoderma associated with the application of hair rinses
      and permanent and semipermanent hair colors are described. To our knowledge, this
      association has not been previously reported. Although none had evidence of
      pigment loss in other sites, Koebner-induced vitiligo cannot be excluded. In our
      cases hair color ingredients seem to have had a selective toxic effect on
      melanocytes. Further study of pigment loss from hair colors is warranted,
      especially in animal and in vitro assays. Patch testing with putative
      depigmenting agents in patients should be done with caution, so as to minimize
      potential for depigmentation in cosmetically important anatomic sites.

PMID- 8299389
TI  - Cocamidopropyl betaine: the significance of positive patch test results in twelve
      patients.
AB  - Cocamidopropyl betaine is a surfactant coming into wide use in shampoos and other
      cleansing products. Recent reports have implicated it as a potential allergen,
      although it is less irritating than other surfactants such as sodium lauryl
      sulfate. Twelve positive patch test results were seen over a period of fifteen
      months of testing in selected patients. Of these, seven results were thought to
      be relevant. All seven patients with relevant reactions and four of the five with
      uncertain relevance had dermatitis of the head and neck area. It is concluded
      that although cocamidopropyl betaine is not a common allergen, it may be at least
      partially responsible for some cases of allergic dermatitis of the head and neck.

PMID- 8299390
TI  - Spice allergy evaluated by results of patch tests.
AB  - Allergic contact dermatitis caused by spices is well documented; however,
      commercial patch tests are unavailable. Between October, 1991, and August, 1992,
      a series of fifty-five patients with suspected contact dermatitis were tested at
      Ochsner Clinic for sensitivity to a group of spices at concentrations of 10
      percent and 25 percent in petrolatum. Concordant patch test results (positive at
      concentrations of 10 percent and 25 percent) were most common with ginger
      (seven), nutmeg(five), and oregano (four); the remaining spices produced zero or
      one positive responses. Patients exhibiting positive reactions at only one
      concentration were more likely to do so at 25 percent: nutmeg (five), ginger and
      cayenne (four), curry, cumin, and cinnamon (three), turmeric, coriander, and sage
      (two), oregano (one), and basil and clove (zero). Solo responses at this level
      may represent a threshold for detecting true allergy or, as an alternative, a
      marginal irritant reaction. Those responding to only 10 percent concentrations
      generally did so weakly. Three patients were deemed to have relevant patch test
      responses to spices.

PMID- 8299391
TI  - Allergic contact dermatitis to topical glucocorticosteroids.
AB  - During the past decade, the reported incidence of allergic reactions to topically
      applied glucocorticosteroids has increased significantly. The two cases reported
      here typify the presenting symptoms of the glucocorticosteroid-allergic persons.
      These cases also illustrate the extensive cross-reactivity among the different
      topical corticosteroids, as well as the potential for systemic contact dermatitis
      to occur following parenteral exposure. These cases are reviewed in the context
      of the many other reports in the literature of similar allergic reactions.

PMID- 8299392
TI  - Iatrogenic contact dermatitis to proparacaine: an ophthalmic topical anesthetic.
AB  - Allergic contact dermatitis to a topical ophthalmic anesthetic, proparacaine, is
      reported in a patient with refractory glaucoma. His ophthalmologist routinely
      used a preparation containing this anesthetic, which is an uncommon sensitizer,
      for measuring the patient's intraocular pressure. That the patient did not apply
      the medication himself resulted in added difficulty in discovering the
      iatrogenically induced contact allergy. Avoidance of this anesthetic resulted in
      resolution of the patient's recurrent bouts of periocular dermatitis and
      conjunctivitis. The importance of testing patients suspected of having contact
      allergy to all medications to which they are exposed is emphasized.

PMID- 8299393
TI  - All the things I knew were true about contact dermatitis that aren't.
AB  - Twenty-five years of experience in evaluating people with irritant and allergic
      contact dermatitis has taught me that many of my preconceived notions were false.
      No patients are more challenging and interesting to investigate or more rewarding
      to help than those with long-standing histories of undiagnosed contact
      dermatitis. Furious resolve during investigation coupled with a willingness to be
      proven wrong and to find the unexpected is most likely to result in a successful
      outcome for patients with contact dermatitis.

PMID- 8299394
TI  - Update: immediate and delayed hypersensitivity to natural rubber latex.
AB  - Hypersensitivity to natural rubber latex, an ingredient of many medical devices
      and consumer products, appears to be increasing. Chemical additives induce T-cell
      mediated type IV delayed reactions while proteins that occur naturally in latex
      elicit antibody-mediated type I immediate reactions. The latter can be fatal. The
      clinical manifestations of these reactions, the risk factors for developing latex
      hypersensitivity, and diagnostic options are reviewed. The only reliable
      management strategy is allergen avoidance. Therefore, factors that can affect the
      levels of both type I and type II allergens in products are discussed.

PMID- 8299395
TI  - Contact urticaria and anaphylaxis to the fungicide chlorothalonil.
AB  - Chlorothalonil, a common fungicide used for agricultural and horticultural
      purposes is capable of eliciting contact urticaria. In our patient, an
      anaphylactoid reaction resulted from intact skin contact to diluted
      chlorothalonil (0.01 percent aqueous). Our patient also experienced immediate
      respiratory reactions such as a tight chest and throat after entering the nursery
      greenhouse, without direct skin contact with chlorothalonil.

PMID- 8299396
TI  - Cosmetics as causes of allergic contact dermatitis.
AB  - This article reviews the correlation between the nature of cosmetic products and
      the location of lesions in cases of contact dermatitis. It also reviews the
      nature of the most common allergenic products and substances and offers
      guidelines for testing cosmetics in cases of contact allergy.

PMID- 8299397
TI  - Fracture healing and growth hormone. A biochemical study in the rat.

PMID- 8299398
TI  - Clinical and prognostic features of advanced ovarian carcinoma.

PMID- 8299399
TI  - Congenital genetic instability in colorectal carcinomas.
AB  - INTRODUCTION: Oncogenic evolution is probably based on a progressive selection of
      clonal subpopulations from within a single clone. This selection is supposed to
      be based on enhanced genetic instability in the genome. In the vast majority of
      patients this increased lability is supposed to be the result of acquired
      alterations, and once established, it may contribute to the continuing, genetic
      instability within the neoplastic cells. It has been postulated, that inborn
      chromosomal instability is not limited to a few rare syndromes. Indeed, one of
      the common colorectal cancer (CRC) syndromes, familial adenomatous polyposis
      (FAP), is supposed to be a chromosomal instability syndrome. Also the hereditary
      nonpolyposis colorectal cancer syndrome (Lynch Syndrome (LS)) has shown genomic
      instability. Knudson (1971, 1985) has shown, that the same gene can be involved
      in both the hereditary form of a cancer and in the sporadic form of the same
      cancer. Due to the existence of such hereditary chromosomal instability
      syndromes, inherited genetic instability may be of some importance in the
      evolution of sporadic colorectal cancers. METHODS: In vitro research on dermal
      fibroblasts is based on the theory, that all studied cells of an individual carry
      the same genetic material, irrespective of their in vivo expression. Increased in
      vitro tetraploidy (IVT+) in skin fibroblast cultures is supposed to be a
      germinally transmitted expression of genomic instability, with special reference
      to LS. At the same time the chromosomal aberrations, which occur in neoplasms,
      can be measured by flow cytometric DNA analysis. The DNA content, thus measured,
      is supposed to be an expression of somatic acquired genetic instability. Finally,
      since occult mandibular osteomas have been shown to be associated with FAP, we
      have investigated a substantial part of our patients with this phenotypical
      marker. AIM OF STUDY: In CRC the adenoma-carcinoma sequence is widely accepted,
      and the purpose of our investigation was to find a correlation, if any, between:
      Changes in adenoma flow cytometric DNA content and histological grade and type of
      adenomas. Changes in dermal fibroblast IVT+ from adenoma patients and
      histological grade and type of adenomas. Changes in dermal fibroblast IVT+ and
      flow cytometrical DNA content in adenomas and carcinomas from the same patients.
      Furthermore, we wanted to investigate if: The occurrence of IVT+ in skin
      fibroblasts among patients with CRC was different from that of IVT+ among
      patients without colorectal neoplasies. The occurrence of IVT+ in skin
      fibroblasts among patients with CRC was associated with the occurrence of occult
      mandibular osteomas in the same patients. The occurrence of dermal fibroblast
      IVT+ conveyed any prognostic significance in CRC patients. RESULTS AND
      CONCLUSIONS: 1) A significant correlation was found between both the occurrence
      of skin fibroblast IVT+ and adenoma DNA aneuploidy in relation to the degree of
      dysplasia and histological type of adenomas. This signifies, that inborn and
      acquired genetic instability is correlated to the adenoma-carcinoma sequence.
      IVT+ was found to be correlated to the progression of adenomas to carcinomas and
      not to the development of adenomas. 2) A direct correlation between IVT+ and
      adenoma DNA aneuploidy could not be demonstrated. However, among those patients
      with diploid adenomas and IVT+ 57% showed villous adenomas. Among those patients
      with diploid adenomas and IVT- only 14% had villous adenomas. This further
      substantiates the correlation of IVT+ to the adenoma-carcinoma sequence. IVT+ was
      highly associated with DNA aneuploidy in carcinomas, and since IVT+ was found to
      be significantly associated with CRC's with a DNA index > or = 1.5, it is
      suggested that IVT+ mainly is correlated to the early steps in tumor progression.
      3) IVT+ was found in 34% of sporadic CRC, and tumor DNA aneuploidy was
      demonstrated in 73%...

PMID- 8299400
TI  - Cardiac function in insulin-dependent diabetic patients without clinical signs of
      heart disease. Echocardiographic studies with emphasis on the left ventricular
      systolic function.

PMID- 8299401
TI  - Reciprocal inhibition in man.
AB  - Reciprocal inhibition is the automatic antagonist alpha motor neurone inhibition
      which is evoked by contraction of the agonist muscle. This so-called natural
      reciprocal inhibition is a ubiquitous and pronounced phenomenon in man and must
      be suspected of playing a major role in the control of voluntary movements. The
      spinal pathways underlying this inhibitory phenomenon were studied. The
      disynaptic reciprocal Ia inhibitory pathway between the tibial anterior muscle
      and the soleus alpha motor neurones was identified and described in man. It was
      shown that the inhibition can be evoked in most healthy subjects at rest, but the
      degree of inhibition varies considerably from one subject to another. It was
      concluded that it corresponds to the disynaptic reciprocal Ia inhibitory pathway
      which has been extensively described in animal experiments. The disynaptic
      reciprocal inhibition was shown to increase during the dynamic phase of a
      dorsiflexion movement of the foot, but not during the tonic phase. However, when
      the peripheral afferent feedback from the contracting muscle was blocked by
      ischaemia, an increase of the inhibition was revealed also during the tonic phase
      of the dorsiflexion. The concealment of this increase during unrestrained
      peripheral feedback from the muscle was thought to be due to the post-activation
      depression mechanism; a mechanism which was described further and which probably
      involves reduced transmitter release at Ia afferent terminals as a result of
      previous activation of these afferent fibers. Hence the hypothesis was supported
      that alpha motor neurones and the corresponding inhibitory interneurones, which
      project reciprocal inhibition to the antagonist motor neurones, are activated in
      parallel during voluntary contraction of agonist muscles. An additional
      reciprocal inhibitory mechanism, the long latency reciprocal inhibition, was
      described between the tibial anterior muscle and the soleus alpha motor neurones.
      It was shown to be evoked by group I afferent activity and it was seen at a
      conditioning-test interval of 3-6 msec. It was initiated by supraspinal pathways
      and it was seen only during dorsiflexion of the foot. The pathway underlying this
      inhibitory mechanism is unknown, but it was suggested that it was mediated by a
      propriospinal pathway. The possible contribution to reciprocal inhibition of
      presynaptic inhibition of soleus Ia afferent fibers was studied by an indirect
      method. It was concluded that this presynaptic inhibition was increased during
      even slight dorsiflexion of the foot and that the increase was mainly dependent
      upon the peripheral afferent input from the contracting muscle.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8299402
TI  - On the role of atrial natriuretic factor in normotensive and hypertensive man.
      With special emphasis on lithium clearance in the assessment of renal tubular
      sodium handling.

PMID- 8299403
TI  - The cholecystokinin receptor on the gallbladder.

PMID- 8299404
TI  - NORA--Nordic research on ageing. Functional capacity of 75-year-old men and women
      in three Nordic localities.
AB  - The aim of this cross-national study was to describe and compare differences in
      functional capacity of 75-year old people in three Nordic urban localities. As
      the life-expectancy at the age of 75 differs between the Nordic countries, there
      is reason to look for similar differences in functional capacity, taking
      differences in socio-demography, lifestyle, living conditions and health into
      consideration. In 1989-1991, 400 75-year-old men and women were selected to
      represent 75-year-olds in a Danish, Finnish and Swedish city. They participated
      in examinations which focused on functional capacity and health, where identical
      questionnaires, tests, and equipment were employed. The methods employed were
      developed from the experience gathered during previous studies of epidemiology of
      ageing in Glostrup, Gothenburg, and Jyvaskyla. Functional capacity is the
      dependent variable multifactorially related to age, health, living conditions,
      and life style. The data collection was performed with participation rates in the
      interviews of 85% in Glostrup, 83% in Gothenburg, and 92% in Jyvaskyla. The
      participation rates in the laboratory examinations were 76%, 67% and 77%,
      respectively. Examples of differences in socio-demographic background, lifestyle
      and measures of health and performance in the three localities are given. The
      Nordic study on physical, psychological and social capacity of 75-year-olds was
      performed with sufficiently standardised methods to allow a comparison of the
      results. Similar comprehensive cross-sectional comparative studies of the elderly
      people have not been performed earlier. Local and cross-national results will be
      published in each field separately and in combination.

PMID- 8299405
TI  - Disodium-ethylene diamine tetraacetic acid (EDTA) has no effect on blood lipids
      in atherosclerotic patients. A randomized, placebo-controlled study.
AB  - OBJECTIVE: To study whether intravenous disodium-ethylene diamine tetraacetic
      acid (EDTA) affects blood lipids in patients with intermittent claudication.
      DESIGN: Double-blind, randomized, placebo-controlled trial. PARTICIPANTS: Twenty
      nine patients with intermittent claudication (systolic ankle-brachial blood
      pressure index < 0.8; pain free walking distance 50-200 m). INTERVENTION: 3 g
      EDTA or placebo (isotonic saline) per infusion over a period of 5-9 weeks to a
      total of 57 g EDTA. Patients received vitamins, minerals and trace-elements
      daily. RESULTS: 14 patients received EDTA and 15 placebo. There was no
      statistically significant difference in the plasma concentration of cholesterol,
      low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)
      cholesterol or triglyceride between the 2 groups. CONCLUSION: Treatment with EDTA
      does not alter blood lipids in patients with intermittent claudication.

PMID- 8299406
TI  - Effects of intravenous EDTA treatment on serum parathyroid hormone (1-84) and
      biochemical markers of bone turnover.
AB  - Patients with primary hyperparathyroidism have increased bone turnover, but it is
      less well documented how brief periods of excess parathyroid hormone (PTH)
      (endogenous or exogenous) affect bone metabolism. In the present double blind
      study, we examined the effect of either ethylenediaminetetraacetatic acid (EDTA)
      or placebo on serum levels of PTH and biochemical markers of bone turnover in 15
      women and 39 men (aged 41 to 81 years) suffering intermittent claudication due to
      atherosclerosis. Disodium EDTA was administered as 20 repeated infusions of 3
      grams during a period of 5-9 weeks. Serum calcium and serum phosphate decreased
      following treatment (p < 0.001) and remained unchanged in the placebo group.
      However, the differences between the groups were insignificant (ANOVA p = 0.13
      and p < 0.10, respectively). PTH increased 2 1/2 fold following EDTA treatment (p
      < 0.001, ANOVA). The change in serum PTH was inversely correlated with the change
      in serum calcium (r = -0.53, p < 0.01). In the EDTA group, urinary
      hydroxyproline/creatinine and calcium/creatinine increased after treatment (ANOVA
      p < 0.001 and p < 0.05, respectively). Serum bone alkaline phosphatase decreased
      significantly in the EDTA group immediately after treatment (p < 0.001, ANOVA)
      and returned to baseline level at three months while only an insignificant
      decrease in serum osteocalcin was seen following treatment. We conclude that EDTA
      treatment increases endogenous PTH secretion considerably and leads to increased
      bone resorption. However, no changes in osteoblastic markers indicating increased
      activation of bone remodeling could be demonstrated. Our findings support that
      chelation therapy with EDTA is accompanied by bone loss.

PMID- 8299407
TI  - The link between domestic violence and child abuse: assessment and treatment
      considerations.
AB  - This article discusses the existence of both spouse abuse and child abuse within
      families. Recent research suggests that practitioners have often missed the
      coexistence of these problems within their caseloads. Practice implications for
      both domestic violence service providers and child welfare professionals are
      outlined. Recommendations for changes in assessment procedures, treatment
      planning, and implementation are made.

PMID- 8299408
TI  - Adoption and donor insemination: factors influencing couples' choices.
AB  - The increasing availability of donor insemination (DI) gives couples faced with
      male infertility a choice between DI and adoption, and for many, DI is now the
      preferred option. The results of a study of 54 couples who gave birth to a child
      or children by means of DI are presented both quantitatively and qualitatively,
      and show that most couples who have children by DI have considered adoption.
      Their reasons for choosing DI range from the practical to the emotional, from
      perceived negative aspects of adoption to perceived advantages of DI. This
      article discusses these perceptions and their implications.

PMID- 8299409
TI  - Preparing practitioners for child welfare practice with substance-abusing
      families.
AB  - Child welfare practice and substance abuse treatment have become overlapping
      areas for many human service professionals. This article stresses the importance
      of combining perspectives, calling for the child welfare and alcohol and other
      drug (AOD) abuse treatment systems to deal with both the mother's recovery and
      the child's well-being. Changes in attitudes, knowledge, and skills are required
      on the part of both the child welfare practitioner and the AOD abuse treatment
      worker.

PMID- 8299410
TI  - Assessing the benefits and increasing the utility of addiction training for
      public child welfare workers: a pilot study.
AB  - Abuse of alcohol or other drugs is at the root of many child welfare problems,
      yet most workers receive little academic training to cope with these difficulties
      in their clients. Continuing education is a useful tool to facilitate the
      adoption of attitudes necessary for effective response to addicted persons.
      Workers may not approach continuing education with an eye to identifying specific
      opportunities for changing their practice, however, and impediments in the
      workplace make implementing change difficult. Continuing education is most
      effective if supervisors help in setting goals, removing obstacles, and
      facilitating workers' efforts to incorporate into practice what they learn in the
      training classroom.

PMID- 8299412
TI  - The GTPase superfamily. Symposium, London, 17-19 November 1992. Proceedings.

PMID- 8299411
TI  - The prevention and treatment of child abuse in households of substance abusers: a
      research demonstration progress report.

PMID- 8299413
TI  - The GTPase superfamily. Introduction.

PMID- 8299414
TI  - The G protein cascade of visual transduction: kinetics and regulation.
AB  - In retinal rods photoexcited rhodopsin (R*) catalyses the activation of
      transducin (T) by GTP, which in turn activates the cGMP phosphodiesterase (PDE).
      The ensuing decrease in cGMP concentration reduces the cell membrane's channel
      conductance. To account for the kinetics of the response to light, all underlying
      biochemical reactions must reach maximum speed and be turned off within a second.
      Kinetic analysis of transducin activation suggests that because of the fast
      lateral diffusion of T, the rate-limiting step is not the collision between R*
      and T but the entry of GTP after the release fo GDP from the R*-bound T alpha. T
      alpha-GTP dissociates from both R* and T beta gamma and diffuses through the
      cytoplasm to activate PDE. In suspensions of bovine rod outer segments, time
      resolved microcalorimetry yields rates of approximately 1-2 s-1 for the GTPase of
      T alpha and the correlated deactivation of PDE. But for isolated T alpha-GTP the
      single turnover GTPase rate measured by a stopped-flow technique is only 0.05 s
      1. To activate PDE, T alpha-GTP binds tightly to the PDE gamma subunit. In vitro
      the soluble T alpha-GTP.PDE gamma complex dissociates from activated PDE alpha
      beta. Thus PDE gamma might be the GTPase activator of T alpha, but no GTPase
      acceleration was observed in isolated T alpha-GTP.PDE gamma. The GTPase
      activation must depend on the interaction of T alpha-GTP.PDE gamma with membrane
      bound PDE alpha beta.

PMID- 8299415
TI  - Voltage-dependent Ca2+ channels as GAPs.

PMID- 8299416
TI  - Regulators of small GTPases.
AB  - Small GTPases are converted from the GDP-bound inactive form to the GTP-bound
      active form by a GDP/GTP exchange reaction which is regulated by GDP/GTP exchange
      proteins (GEPs). We have found both stimulatory and inhibitory GEPs, which we
      have named GDP dissociation stimulators (GDSs) and GDP dissociation inhibitors
      (GDIs) respectively. We have isolated Smg GDS, Rho GDI and Rab GDI, cloned them,
      and determined their primary structures. These GEPs are active on a group of
      small GTPases: Smg GDS on at least K-Ras, Rap1/Smg21, Rho and Rac; Rho GDI on at
      least Rho, Rac and Cdc42; Rab GDI on most of the Rab family members. These GEPs
      have an additional function, regulating the translocation of their substrate
      small GTPases between the membrane and the cytosol. The GEPs interact only with
      the post-translationally modified form of their substrate small GTPases.

PMID- 8299417
TI  - A GTPase cycle in initiation of protein translocation across the endoplasmic
      reticulum membrane.
AB  - In higher eukaryotes proteins bearing a signal sequence are translocated across
      the membrane of the endoplasmic reticulum (ER). The initial events of protein
      translocation are the binding of the signal sequence by the 54 kDa subunit
      (SRP54) of the signal recognition particle (SRP) and the targeting of the
      ribosome nascent chain complex to the ER. Targeting is mediated by the binding of
      SRP to the SRP receptor, a membrane protein comprising two different subunits, SR
      alpha and SR beta. Interaction of SRP and SR alpha/SR beta causes release of the
      signal and the engagement of the nascent chain with the membrane-bound
      translocation apparatus. Both SRP54 and SR alpha contain homologous domains which
      include a predicted GTPase fold. The transmembrane protein SR beta also contains
      a GTPase domain, but it is not closely related to those of SRP54 and SR alpha.
      All three proteins bind GTP specifically, and the SR alpha/SR beta complex
      stimulates both GTP binding to and GTP hydrolysis by SRP54. We suggest a model
      for the initiation of protein translocation across the ER in which SR alpha beta
      catalyses a cycle of GTP binding, hydrolysis and release by SRP54 that regulates
      its dissociation from the signal sequence.

PMID- 8299418
TI  - A cell-physiological description of GE, a GTP-binding protein that mediates
      exocytosis.
AB  - Introduction of GTP gamma S or other non-metabolic analogues of GTP into
      permeabilized myeloid granulocytes (mast cells, eosinophils, neutrophils)
      constitutes a sufficient stimulus to induce exocytosis. We concentrate on mast
      cells. Exocytosis from cells permeabilized in isotonic glutamate solution
      proceeds in the absence of ATP and at exceedingly low levels (< 10(-9) M) of
      Ca2+. Mg2+ strongly promotes GTP gamma S-induced exocytosis but this requirement
      can be spared and then obliterated by lifting Ca2+ through 10(-7) to 10(-6) M.
      GTP provides only a modest support to exocytosis but becomes almost equipotent
      with GTP gamma S when Mg2+ is excluded. Ca2+ alone is unable to induce
      exocytosis. We envisage that the terminal stage of exocytosis (membrane fusion)
      requires activation of GE, a putative GTPase so far undefined as a molecular
      entity. Ca2+, presumed to act through a Ca(2+)-binding protein (CE, also
      undefined) supports exocytosis by promoting the exchange of guanine nucleotides
      on GE. In the absence of Mg2+ the onset of exocytosis is characterized by delays
      that have concentration-dependent (binding) and independent components. The
      latter are sensitive to the identity of the stimulating nucleotide (GTP < GTP
      gamma S < Gpp [NH]p) and may reflect activation of GE. The activation by Ca2+ and
      Mg2+ and the delays preceding onset of GTP gamma S-triggered exocytosis are
      reminiscent of the action of glucagon and Mg2+ in the activation of adenylate
      cyclase in hepatocyte membranes. The cell-physiological description predicts GE
      to be an alpha beta gamma heterotrimeric GTP-binding protein with functional
      similarity to GS.

PMID- 8299419
TI  - Dynamin, a GTPase involved in the initial stages of endocytosis.
AB  - Dynamin is a high molecular mass (100 kDa) GTPase which binds to and co-purifies
      with microtubules. Molecular cloning of rat brain dynamin has revealed the three
      well-established consensus sequence elements for GTP binding within the N
      terminal third of the protein, as well as sequence similarity within this region
      to the interferon-inducible antiviral Mx proteins, the product of the yeast
      membrane sorting gene VPS1, and the product of the yeast mitochondrial
      replication gene MGM1. More extensive sequence similarity between rat dynamin and
      the product of the Drosophila gene shibire, which is involved in endocytosis, has
      also been found. In in vitro assays microtubules strongly stimulate the dynamin
      GTPase. This effect can be reversed by removal of the dynamin C-terminus using
      papain, which abolishes microtubule binding. Overexpression of mutant forms of
      dynamin in vivo using Cos-7 cells inhibits transferrin uptake and alters the
      distribution of clathrin and of alpha-adaptin, but not gamma-adaptin. Deletion of
      the C-terminus of mutant forms of dynamin abolishes these effects. Together these
      results suggest a critical role for dynamin in the early stages of endocytosis.
      It is uncertain whether microtubules interact with dynamin in vivo or whether the
      in vitro effects of microtubules mimic the effects of other regulatory elements
      in vivo.

PMID- 8299420
TI  - The VPS1 protein is a dynamin-like GTPase required for sorting proteins to the
      yeast vacuole.
AB  - VPS1 encodes a 79 kDa protein required for the proper sorting of soluble vacuolar
      proteins in Saccharomyces cerevisiae. The N-terminal half of Vps1p, which
      contains a consensus GTP-binding motif, shares extensive homology with a growing
      family of high molecular mass GTP-binding proteins. Members of this family have
      been implicated in a number of cellular processes. Vps1p most closely resembles
      the microtubule-associated protein dynamin. As predicted from the sequence, Vps1p
      binds and hydrolyses GTP. However, no requirement for microtubules was found for
      Vps1p function in protein sorting. In subcellular fractionation experiments Vps1p
      associates with the membrane fraction; the C-terminal half of Vps1p is important
      for this association. Mutational analysis of VPS1 generated two classes of
      mutations, dominant negative and recessive. The dominant mutations all mapped to
      the N-terminal half of the protein. Recessive mutations gave rise to either
      truncated or unstable proteins. A potential Vps1p-interacting protein (Mvp1p) has
      been isolated by screening for suppressors of the dominant alleles of VPS1. Taken
      together these results suggest that Vps1p is a two-domain protein that is part of
      a multi-subunit protein complex involved in vacuolar protein sorting.

PMID- 8299421
TI  - Ras-mediated signalling pathway during vulval development in Caenorhabditis
      elegans.

PMID- 8299422
TI  - The cycle of SEC4 function in vesicular transport.
AB  - Sec4 is a Ras-like GTP-binding protein required for exocytosis in yeast. Unlike
      Ras, it is the ability of Sec4 to cycle between the GTP- and GDP-bound forms
      rather than the absolute levels of the GTP-bound form that is critical for
      function. This cycle may be coupled to an observed cycle of Sec4 localization
      within the cell. Sec4 binds to secretory vesicles which then fuse with the plasma
      membrane in exocytosis. Sec4 can recycle from the plasma membrane through a
      soluble pool to rebind to a new round of vesicles. We have found an activity in
      yeast (Saccharomyces cerevisiae) comparable to that of the GDP dissociation
      inhibitor protein isolated from mammalian cells that releases GDP-bound Sec4 from
      membranes. DSS4-1, a dominant suppressor of the sec4-8 temperature-sensitive
      mutation, encodes a nucleotide exchange protein. The cycle of Sec4 may function
      to allow the assembly and subsequent disassembly of a set of proteins necessary
      for exocytosis. Candidates for members of this set of proteins are encoded by sec
      genes which show strong genetic interactions with sec4-8. Two of these (SEC8 and
      SEC15) encode large proteins which form a complex that is peripherally associated
      with the plasma membrane.

PMID- 8299423
TI  - Should the tubulins be members of the GTPase superfamily?
AB  - The beta-subunit of the alpha/beta tubulin heterodimer resembles other members of
      the GTPase superfamily in that: it binds GTP, the GTP is hydrolysed to GDP on
      microtubule assembly and this induces a conformational change; it exhibits a
      similar nucleotide stereospecificity; aluminium and beryllium fluorides inhibit
      this hydrolysis-dependent conformational change; and beta-tubulin contains
      peptides which are similar to the consensus motifs characteristic of the GTPase
      superfamily proteins. By contrast, UV photo-cross-linking and other binding
      studies have identified peptides which may contribute to the GTP-binding site but
      which are absent from the GTPase superfamily proteins. We suggest that beta
      tubulin has a 'dual personality', with the characteristics of the GTP-binding
      site depending upon the precise conformation of the protein and upon whether the
      experimental assays probe nucleotide binding or the hydrolytic mechanism. We
      suggest that the hydrolytic mechanism of beta-tubulin resembles that of the other
      members of the GTPase superfamily, although the differences within the consensus
      motifs dictate that the architecture of the GTP pocket cannot be identical.

PMID- 8299424
TI  - Elongation factors in protein synthesis.
AB  - Recent discoveries of elongation factor-related proteins have considerably
      complicated the simple textbook scheme of the peptide chain elongation cycle.
      During growth and differentiation the cycle may be regulated not only by factor
      modification but also factor replacement. In addition, rare tRNAs may have their
      own rare factor proteins. A special case is the acquisition of resistance by
      bacteria to elongation factor-directed antibiotics. Pertinent data from the
      literature and our own work with Escherichia coli and Streptomyces are discussed.
      The GTP-binding domain of EF-Tu has been studied extensively, but little
      molecular detail is available on the interactions with its other ligands or
      effectors, or on the way they are affected by the GTPase switch signal. A growing
      number of EF-Tu mutants obtained by ourselves and others are helping us in
      testing current ideas. We have found a synergistic effect between EF-Tu and EF-G
      in their uncoupled GTPase reactions on empty ribosomes. Only the EF-G reaction is
      perturbed by fluoroaluminates.

PMID- 8299425
TI  - RAS function and protein kinase cascades.
AB  - This paper reviews recent progress in understanding the function of RAS in three
      systems: the budding yeast (Saccharomyces cerevisiae), the fission yeast
      (Schizosaccharomyces pombe) and Xenopus laevis oocytes. One of the functions of
      RAS in S. cerevisiae is the stimulation of adenylate cyclase. This leads to the
      activation of the cAMP-dependent protein kinases--a function that has probably
      not been conserved in evolution. The immediate function of RAS in S. pombe is not
      known, but it may lead to the activation of a protein kinase cascade. This
      cascade has likely been conserved in evolution and linkage between it and RAS can
      be demonstrated in cell-free extracts from Xenopus oocytes. The Xenopus cell-free
      system provides a means to test specific hypotheses about RAS function and to
      isolate targets of RAS.

PMID- 8299426
TI  - Three-dimensional structure and properties of wild-type and mutant H-ras-encoded
      p21.
AB  - Ras (or p21) is the product of the ras proto-oncogene and is believed to be
      involved in growth-promoting signal transduction. The structure of the guanine
      nucleotide-binding domain of H-Ras (or p21H-ras) in the triphosphate conformation
      was determined at very high resolution (1.4 A). All the binding interactions
      between protein and Gpp[NH]p and Mg2+ can be resolved in great detail. The region
      around amino acids 61-65 is flexible and exists in two conformations, one of
      which seems to be important for catalysis. The properties and structures of
      several oncogenic and non-oncogenic mutant forms of Ras have also been
      determined. Since the structure of the GDP-bound form is also known, the nature
      of the conformational change from the GTP-bound to the GDP-bound form can be
      inferred from the 3-D structure. A mechanism for the intrinsic GTP hydrolysis has
      been proposed. Its implications for the GAP-stimulated GTPase reaction is
      discussed in the light of recent kinetic and mutational experiments.

PMID- 8299427
TI  - Cell transformation by ras and regulation of its protein product.
AB  - We are studying the biological activity and regulation of mammalian Ras protein
      in tumours and in physiological signalling. We have shown that GAP (the GTPase
      activating protein) is a potent negative regulator of normal Ras in cells.
      Reduction or loss of the NF1 gene product neurofibromin, in association with
      genetic abnormalities of the NF1 locus, has been identified in schwannoma cell
      lines from patients with neurofibromatosis and in melanoma and neuroblastoma
      lines from patients without neurofibromatosis. Although loss of neurofibromin in
      the schwannoma lines was associated with a high proportion of normal Ras protein
      in the active GTP-bound state, Ras-GTP appeared to be appropriately regulated in
      the melanoma and neuroblastoma lines, which contain normal levels of GAP.
      Therefore the GTPase-activating activity of neurofibromin is not essential for
      negative regulation of Ras in some cell types and the putative tumour suppressor
      function of neurofibromin in such cell types is independent of its GTPase
      activating activity. Mitogen activation of Ras in fibroblasts is mediated
      primarily by exchange factors, which probably interact with a region on the Ras
      protein distinct from the region required for interaction with GAP. Multiple full
      length cDNAs have identified a mouse gene whose products are related to yeast
      CDC25 guanine nucleotide exchange factor.

PMID- 8299428
TI  - Identification of ras targets using a genetic approach.
AB  - The Sevenless receptor tyrosine kinase is required for the development of the R7
      photoreceptor cell in the Drosophila eye. Several components of the Sevenless
      signal transduction pathway have been identified in genetic screens for
      enhancers/suppressors of the sevenless phenotype. These studies suggest that
      activation of Sevenless leads to stimulation of Ras1 activity, whereas Gap1
      appears to act as a negative regulator of the pathway. Inactivation of the Gap1
      locus causes transformation of non-neuronal cone cells into supernumerary R7
      cells. This same mutant phenotype is observed when activated Ras1 is expressed
      under the control of the sevenless promoter. While studies in other organisms
      have demonstrated a role for ras gene products in signal transduction, the
      effectors of Ras activity have not yet been identified. We are carrying out
      genetic screens for enhancers and suppressors of the Gap1 and activated Ras1
      phenotypes in the hope of identifying genes encoding some of these effectors. We
      are conducting chemical mutagenesis screens and have also screened existing
      collections of P element lines. A molecular characterization of the most
      promising mutations is in progress.

PMID- 8299429
TI  - G proteins in signal transduction: the regulation of phospholipase C.
AB  - The hydrolysis of phosphatidylinositol 4,5-bisphosphate by specific phospholipase
      C (PLC) enzymes produces two second messengers, inositol 1,4,5-trisphosphate and
      diacylglycerol. Heterotrimeric guanine nucleotide-binding regulatory proteins (G
      proteins) of the Gq subfamily activate the PLC beta 1 isoform of PLC. We have
      purified three isozymes of PLC beta: PLC beta 1 and PLC beta 3 from rat brain and
      PLC beta 2 from HL-60 cells. Whereas the beta 1 and beta 2 isozymes appear
      restricted to a few cell types, beta 3 is broadly distributed. Gq alpha (the
      alpha subunit of the Gq subfamily) can activate all three isoforms but PLC beta 2
      is much less sensitive. Thus all three enzymes are potential effectors for
      pertussis toxin-insensitive regulation by hormones. The three beta isozymes can
      also be activated by purified beta gamma subunits. The PLC beta 3 isoform gives
      the greatest activation with beta gamma; PLC beta 1 is least responsive. The
      results indicate that all the known isoforms of mammalian PLC beta can be
      regulated at unique sites by both Gq alpha and beta gamma subunits. The effect of
      beta gamma subunits may provide a pathway for the regulation of PLC beta isozymes
      by pertussis toxin-sensitive G proteins or may indicate that the alpha subunit of
      Gq and its associated beta gamma both participate in regulation of the same
      phospholipase molecule.

PMID- 8299430
TI  - Systolic blood pressure relates to the rate of decline of glomerular filtration
      rate in type II diabetes.
AB  - OBJECTIVE: To relate deterioration in kidney function to some potential
      cardiovascular risk factors in type II diabetic patients. RESEARCH DESIGN AND
      METHODS: Twenty-four normoalbuminuric and 13 microalbuminuric patients completed
      a 3.4-yr prospective observational study. Glomerular filtration rate, urinary
      albumin excretion rate, blood pressure, glycemic control, and lipids were
      measured on entry and at the end of the study. Of the patients, 19
      normoalbuminuric and 8 microalbuminuric (73%) patients had no history of
      antihypertensive treatment. RESULTS: The glomerular filtration rate was
      significantly reduced during the follow-up period (-1.34 +/- 0.54 ml.min-1.1.73 m
      2 [mean +/- SE], P < 0.02). The rate of decline varied considerably in
      normoalbuminuric and microalbuminuric patients (from -13.5 to 4.3 and from -7.0
      to 4.2 ml.min-1.1.73 m-2 per year, respectively) but was on average not
      accelerated in normoalbuminuric or microalbuminuric patients (-1.3 +/- 0.7 and 
      1.5 +/- 0.8 ml.min-1.1.73 m-2 per year, respectively). Significant correlations
      were observed between the glomerular filtration rate fall rate and initial
      systolic blood pressure (r = -0.47, P < 0.01; patients without antihypertensive
      treatment: r = -0.42, P = 0.03) but not diastolic blood pressure. In a stepwise
      multiple linear regression analysis, baseline systolic blood pressure
      significantly determined the fall rate of the glomerular filtration rate
      (regression coefficient = -0.050, SE = 0.018, P = 0.011; patients without
      antihypertensive treatment: regression coefficient = -0.047, SE = 0.021, P =
      0.030). CONCLUSIONS: In these type II diabetic patients neither normoalbuminuria
      nor microalbuminuria are at an average associated with an accelerated decline in
      kidney function. Still, systolic blood pressure is a determining factor for the
      rate of decline in the glomerular filtration rate. A longer follow-up time with
      consecutive glomerular filtration rate measurements are needed to determine the
      long-term implications of normoalbuminuria and microalbuminuria on kidney
      function in type II diabetic patients.

PMID- 8299431
TI  - Daily vitamin E supplements improve metabolic control but not insulin secretion
      in elderly type II diabetic patients.
AB  - OBJECTIVE: To investigate the potential metabolic benefits deriving from daily
      vitamin E administration in type II diabetic patients. RESEARCH DESIGN AND
      METHODS: Twenty-five type II diabetic patients were invited to randomly take
      placebo or vitamin E (d-alpha-tocopherol; 900 mg/day) along a similar 3-mo period
      in a double-blind, crossover procedure. A wash-out period of 30 days separated
      the two treatment periods. At the end of each treatment period blood samples were
      drawn for plasma metabolites determination, and an intravenous glucose tolerance
      test (25 g of glucose as bolus in 3 min) was performed. During this study oral
      hypoglycemic agents were not discontinued or changed in their dosage. RESULTS:
      Chronic vitamin E administration reduced plasma glucose (8.3 +/- 0.3 vs. 7.5 +/-
      0.2 mM, P > 0.05), triglycerides (2.27 +/- 0.08 vs. 1.67 +/- 0.09 mM, P < 0.02),
      free fatty acids (786 +/- 116 vs. 483 +/- 64 mM), total cholesterol (6.74 +/-
      0.09 vs. 5.50 +/- 0.10 mM, P < 0.05), low-density lipoprotein cholesterol (4.73
      +/- 0.11 vs. 3.67 +/- 0.07 mM, P < 0.04), and apoprotein B (1.7 +/- 0.3 vs. 1.0
      +/- 0.1 g/L) levels but did not affect beta-cell response to glucose. HbA1 levels
      (7.8 +/- 0.3 vs. 7.1 +/- 0.5%, P < 0.05) were also significantly lowered after
      chronic vitamin E administration. CONCLUSIONS: Daily vitamin E supplements seem
      to produce a minimal but significant improvement in the metabolic control in type
      II diabetic patients. More studies are necessary before conclusions can be drawn
      about the safety of vitamin E during long-term administration.

PMID- 8299432
TI  - Neurophysiological impairments in IDDM patients during euglycemia and
      hypoglycemia.
AB  - OBJECTIVE: To test the hypothesis that latencies of evoked potentials in IDDM
      patients are delayed compared with healthy control subjects during euglycemia,
      and that insulin-induced hypoglycemia causes further latency delays of evoked
      potentials to occur. RESEARCH DESIGN AND METHODS: We recruited 23 IDDM patients
      (27.9 +/- 1.6 yr of age, HbA1c 6.7 +/- 0.3%, without sensory or autonomic
      neuropathy) and 26 unequivocally healthy subjects who were carefully matched for
      sex, age, and body mass index to serve as the control group (18 men and 8 women,
      28.4 +/- 1.6 yr of age, 22.6 +/- 0.7 kg/m2), for a controlled, prospective study.
      Sequential euglycemic-hypoglycemic clamps were performed with stable glycemic
      plateaus of 5.6, 3.3, 2.2, and 1.7 mM, at which the patients' and healthy control
      subjects' neurophysiological functions were evaluated. The methodological
      armamentarium included the measurement of brainstem auditory, middle-latency
      auditory, and somatosensory evoked potentials that assessed conduction velocity
      in corresponding neural structures and information processing in the midbrain and
      auditory cortex. RESULTS: Multiple analysis of variance revealed a significant
      overall difference of brainstem auditory evoked potential latencies during
      euglycemia between the study group and healthy control group (F = 3.41, P <
      0.03), which was mainly attributable to latency delays of wave III (F = 6.60, P <
      0.02), V (F = 9.19, P < 0.01), and interpeak latency I-V (F = 2.82, P < 0.07).
      Repeated analysis of variance measures detected a significant latency delay of
      the major wave Pa of the middle-latency auditory evoked potentials during
      hypoglycemia (F = 4.4, P < 0.02), which rapidly returned to normal after
      reinstitution of euglycemia. CONCLUSIONS: In IDDM patients, chronic, structural
      CNS changes already appear at the brainstem level during euglycemia. Functional,
      reversible CNS changes, however, seem to emerge during acute deviation from
      glucose homeostasis in more rostral brain regions.

PMID- 8299433
TI  - Symptoms of sensory neuropathy in adults with NIDDM in the U.S. population.
AB  - OBJECTIVE: To ascertain the prevalence and determinants of sensory neuropathy
      symptoms through structured interview of a representative sample of people with
      diabetes in the U.S. population. RESEARCH DESIGN AND METHODS: The 1989 National
      Health Interview Survey consisted of a representative sample of 84,572 persons in
      the U.S. > or = 18 yr of age. A household respondent identified all people in the
      household believed to have diabetes (n = 2829). Subjects who could not be
      personally interviewed (n = 129) and individuals who stated they did not have
      diabetes (n = 295) were excluded. A detailed questionnaire was administered to
      99.3% of the remaining 2405 subjects. Questions on symptoms of sensory neuropathy
      included whether during the past 3 mo the subjects had experienced numbness or
      loss of feeling, pain or tingling, or decreased ability to feel hot or cold. The
      neuropathy questions were also administered to a representative sample of 20,037
      subjects who were not known to have diabetes. RESULTS: Prevalence of symptoms of
      sensory neuropathy was 30.2% among people with IDDM. This prevalence was 36.0%
      for men with NIDDM and 39.8% for women with NIDDM, compared with 9.8 and 11.8%
      for nondiabetic men and women, respectively. In logistic regression, factors
      independently related to symptoms of sensory neuropathy in people with NIDDM
      included duration of diabetes, hypertension, hyperglycemia, and glycosuria. Long
      duration of NIDDM (> or = 20 yr) was associated with a twofold increased risk of
      symptoms of sensory neuropathy compared with those with 0-4 yr of diabetes.
      Hypertension was associated with a 60% higher likelihood of symptoms. Diabetic
      individuals whose blood glucose was high all or most of the time or whose urine
      tests showed glucose all of the time were > 2 times as likely to have symptoms of
      sensory neuropathy than those who did not report hyperglycemia or glycosuria.
      Age, sex, ethnicity, cigarette smoking, and height were not determinants of
      sensory neuropathy. CONCLUSIONS: Symptoms of sensory neuropathy affect 30-40% of
      diabetic patients in the U.S. Men and women are affected equally. Prevalence of
      these symptoms increases with longer duration of diabetes; hypertension and
      hyperglycemia predispose to symptoms of sensory neuropathy.

PMID- 8299434
TI  - The role of diet behaviors in achieving improved glycemic control in intensively
      treated patients in the Diabetes Control and Complications Trial.
AB  - OBJECTIVE: To determine whether specific diet-related behaviors practiced by IDDM
      patients in the intensive treatment group of the Diabetes Control and
      Complications Trial were associated with lower HbA1c values. RESEARCH DESIGN AND
      METHODS: A questionnaire addressing various aspects of their dietary behavior
      during the previous year in the DCCT was completed by 623 DCCT intensive
      treatment group subjects. The association between self-reported diet behaviors
      and the subject's mean HbA1c during the previous year was evaluated using a
      linear rank test for trend. The goal of intensive treatment was to achieve blood
      glucose and HbA1c levels as close to the nondiabetic range as possible without
      hypoglycemia. RESULTS: Adherence to the prescribed meal plan and adjusting food
      and/or insulin in response to hyperglycemia were significantly associated with
      lower HbA1c levels. Over-treating hypoglycemia and consuming extra snacks beyond
      the meal plan were associated with higher HbA1c levels. Adjusting insulin dose
      for meal size and content and consistent consumption of an evening snack were
      associated, albeit to a lesser degree, with lower HbA1c. CONCLUSIONS: The average
      HbA1c among intensively managed patients who reported that they followed specific
      diet-related behaviors was 0.25 to 1.0 lower than among subjects who did not
      follow these behaviors. Health-care providers may wish to use these results to
      focus clinical care for intensively treated IDDM patients by emphasizing
      counseling on meal plans, prompt response to high blood glucose levels,
      appropriate treatment of hypoglycemia, and consistent snacking behaviors.

PMID- 8299435
TI  - Usual dietary fat intake and insulin concentrations in healthy women twins.
AB  - OBJECTIVE: To evaluate the associations between the usual intake of dietary fats
      and insulin concentrations. Insulin concentrations and insulin resistance have
      been positively related to risk for NIDDM, obesity, hypertension, dyslipidemia,
      and coronary heart disease, yet little is known of the environmental risk factors
      for relative hyperinsulinemia. Insulin resistance can be induced by high-fat
      feeding in laboratory animals; therefore, high-fat diets may increase risks for
      developing NIDDM. RESEARCH DESIGN AND METHODS: Subjects included 544 nondiabetic
      women who participated in the second examination of the Kaiser Permanente Women
      Twins Study (1989-1990). Fasting and 2-h post 75-g glucose load insulin levels
      were determined. Dietary fat intake was assessed by a food frequency
      questionnaire. Generalized least-squares regression analyses for unpaired twin
      data were used to determine the relationship between dietary fat intake and
      insulin levels after adjustment for total calories, age, several behavioral
      variables, and in some models, percentage of body fat and waist-to-hip ratio.
      Associations of dietary fat intake with insulin levels were also evaluated within
      the subset of monozygotic twin pairs (n = 164 pairs) after removal of genetic
      influences by regression analysis of intrapair differences. RESULTS: Among the
      544 individual women, a 20 g/day increase in total dietary fat was associated
      with a higher fasting insulin level (9% [P < 0.001] before and 6% [P < 0.01]
      after adjustment for the obesity variables). Higher intakes of saturated fat,
      oleic acid, and linoleic acid were each positively related to higher fasting
      insulin values. The relation of dietary fat with fasting insulin was
      significantly attenuated among physically active women compared with those who
      were sedentary (P = 0.04), even after adjustment for obesity. Only saturated fat
      intake was significantly associated with 2-h postglucose load insulin level
      before (P = 0.004) but not after adjustment for obesity. Within identical twin
      pairs, total dietary fat was positively related to fasting insulin before (P =
      0.03) but not after adjustment for obesity (P = 0.11). CONCLUSIONS: High intake
      of total dietary fat is positively related to relative fasting hyperinsulinemia
      in nondiabetic women, particularly those who are sedentary. This effect appears
      to be partly mediated by the relation of dietary fat with obesity.

PMID- 8299436
TI  - A prospective study identifying risk factors for discontinuance of insulin pump
      therapy.
AB  - OBJECTIVE: To identify characteristics of adult patients at baseline associated
      with duration of subsequent, continuous, subcutaneous infusion of insulin
      treatment (pump therapy) of type I diabetes. RESEARCH DESIGN AND METHODS: For 6
      wk, patients followed a standardized conventional therapy and kept a record of
      insulin dosages, capillary blood glucose concentrations, and symptomatic
      hypoglycemia. They were then hospitalized. Additional baseline data were obtained
      and pump therapy was started. Survival analysis was used to determine the
      relationship between baseline independent variables or risk factors and duration
      of pump therapy, which is the dependent variable. RESULTS: Of the 68
      participants, 33 (49%) terminated pump therapy after an average of 9.9 mo of
      treatment. Two models (each P < 0.00005) were developed that exhibited a high
      degree of consistency. Of the 6 variables, 5 were common to both models (HbA1,
      autonomic neuropathy, mean amplitude of glycemic excursions, frequency of
      symptoms of hypoglycemia when blood glucose was < 70 mg/dl, and erythema at
      injection sites). The sixth variable in model 1 (insulin dosage) was replaced in
      model 2 by a variable, Adult Self-Efficacy for Diabetes, which was obtained on
      the 33 more recently enrolled patients; this variable related to patient
      perceptions of self-care behaviors. CONCLUSIONS: We found that, at baseline, the
      presence of a high concentration of HbA1 and a low estimation by the patient of
      their ability to treat the disease portend failure of insulin pump therapy as
      evidenced by its discontinuation. This effect is accentuated when clinical
      evidence of autonomic neuropathy is observed. These findings offer guidance in
      selecting patients with type I diabetes for insulin pump therapy.

PMID- 8299437
TI  - Jet-injected insulin is associated with decreased antibody production and
      postprandial glucose variability when compared with needle-injected insulin in
      gestational diabetic women.
AB  - OBJECTIVE: To elucidate the glycemic response and antibody formation in
      gestational diabetic women treated with insulin injected by a needle or a jet.
      The American Diabetes Association's position statement on jet injectors raised
      the concern that "insulin could be denatured as a result of forceful injection
      through a tiny port, which could lead to an increase in antibody formation"
      (Diabetes Care 11:600, 1988). However, the pharmacokinetics of jet-injected
      insulin suggest that it might be useful in controlling postprandial glucose
      levels. METHODS: We randomized 20 women with gestational diabetes mellitus (< 34
      wk gestation) who required insulin to receive either jet-injected or needle
      injected human NPH and regular insulin. Variables of interest were evaluated at
      the start of therapy, weekly until delivery, and 6-wk postpartum that included:
      1) insulin antibodies in the mother and her infant, 2) HbA1c, 3) insulin dose, 4)
      fasting and postprandial glucose levels, and 5) subject acceptance and
      preference. RESULTS: Of the 10 women in the needle group, 6 developed significant
      insulin antibodies compared with 1 of 10 in the jet group (P < 0.001). HbA1c and
      insulin doses were the same in both groups. During the test meal, glucose levels
      in the jet group were significantly lower (P < 0.01), yet none of the women in
      the jet group experienced blood glucose < 70 mg/dl (3.89 mM) at 3-4 h after the
      meal, compared with 5 in the needle group (P < 0.001). Jet injection was
      associated with less variability (P < 0.001) in postprandial glucose values but
      slightly greater variability (P < 0.05) in fasting glucose. Jet-injected insulin
      was more readily accepted by subjects than needle injections. CONCLUSIONS: Jet
      injection is associated with a diminished antibody response and postprandial
      variability compared with needle-injected insulin. Thus, this warrants
      consideration as a therapeutic option for women with gestational diabetes
      mellitus and may also be applicable to nonpregnant, insulin-requiring diabetic
      patients.

PMID- 8299438
TI  - Microalbuminuria in a middle-aged workforce. Effect of hyperglycemia and
      ethnicity.
AB  - OBJECTIVE: To determine the prevalence of microalbuminuria in a mixed, ethnic
      population and to find the extent that ethnic variation in microalbuminuria can
      be explained by abnormal glucose metabolism, obesity, hypertension,
      hypertriglyceridemia, and life-style factors. RESEARCH DESIGN AND METHODS:
      Urinary albumin concentrations were measured in 5467 middle-aged Maori, Pacific
      Islander, and European workers who participated in a health-screening survey of
      46 New Zealand companies. Participants provided a first-voided, morning urine
      sample; had a 75-g oral glucose tolerance test; had weight, height, and blood
      pressure measured; and completed a self-administered questionnaire about past
      medical history and sociodemographic status. RESULTS: A significantly higher
      prevalence of microalbuminuria was found in individuals with new cases of
      diabetes mellitus (24.1%), in cases of diabetes mellitus previously diagnosed
      (20.6%), and in those with impaired glucose tolerance (16.1%) compared with
      nondiabetic individuals (4.0%). Moreover, in the general population, a piecewise
      linear relationship was detected between albuminuria and plasma glucose with
      significant changes of slope corresponding with 2 h plasma glucose concentrations
      (95% confidence interval) of 6.7 (6.4-7.0) and 9.2 (8.6-9.8) mM, respectively.
      After adjusting for sex, obesity, hypertension, hypertriglyceridemia, cigarette
      smoking, and heavy alcohol consumption in a multivariate model, glycemia was the
      most significant determinant of urinary albumin concentrations in all three
      ethnic groups. However, blood glucose concentrations did not completely explain
      the higher relative risk (95% confidence interval) of microalbuminuria in Maori
      (5.97; 4.48-7.78) and Pacific Islander (5.33; 4.13-6.87) workers compared with
      European workers. CONCLUSIONS: Of the variables investigated, hyperglycemia was
      the most important factor explaining the high prevalence of microalbuminuria in
      Maori and Pacific Islander workers compared with the European workers. However,
      only 14.9% of the variation in urinary albumin concentrations was found in our
      multivariate model, and we have speculated on the contribution of other factors
      such as diet and coexisting renal diseases.

PMID- 8299439
TI  - Does familial hypertriglyceridemia predispose to NIDDM?
AB  - OBJECTIVE: To determine the 10-yr incidence of impaired glucose tolerance and
      NIDDM in families with a clustering of endogenous hypertriglyceridemia. RESEARCH
      DESIGN AND METHODS: The prospective population study, where the oral glucose
      tolerance test and the measurement of serum lipids and lipoproteins were
      performed at the baseline examination and after the 10-yr follow-up, was
      conducted on 56 subjects (17-60 yr of age at the baseline). The subjects were
      from six pedigrees with a clustering of endogenous hypertriglyceridemia, and 47
      of these subjects attended the follow-up 10 yr later. RESULTS: In the study
      families, the prevalence of glucose intolerance and NIDDM increased from 15 to
      49% (P < 0.001) and from 2 to 21% (P < 0.001), respectively, over the 10-yr
      period. When grouped according to the baseline serum triglyceride tertiles, 76%
      (P < 0.01) of the family members with highest serum triglycerides were glucose
      intolerant (29% impaired glucose tolerance, 47% NIDDM) at follow-up compared with
      20% of those with lowest serum triglycerides. In discriminant analysis, including
      age, body mass index, treatment with thiazides and beta-blocking agents, and 2-h
      serum insulin concentration, the baseline serum triglycerides still remained as
      an independent predictor of development of impaired glucose tolerance and NIDDM.
      CONCLUSIONS: Families with a clustering of hypertriglyceridemia are at increased
      risk of NIDDM, and in these families elevation of serum triglycerides serves as a
      risk marker of glucose intolerance and NIDDM.

PMID- 8299440
TI  - Survey of physician practice behaviors related to diabetes mellitus in the U.S.
      Physician adherence to consensus recommendations.
AB  - OBJECTIVE: To summarize the frequency of physician adherence to consensus
      recommendations for prevention of diabetic complications. RESEARCH DESIGN AND
      METHODS: Survey data from a nationwide stratified probability sample of primary
      care physicians were analyzed. Adherence to recommendations were reported by
      physician specialty, age-group, and type of diabetes treated. RESULTS: Adherence
      was high for eye exams, blood pressure measurements, neurological and circulatory
      exams, and laboratory procedures using blood. Adherence was low for examination
      of the teeth and gums, examination of the feet, and laboratory procedures
      involving the collection of urine. Internists generally had the highest adherence
      rates and pediatricians the lowest. Reported adherence decreased with physician
      age. Adherence was higher for the management of individuals with IDDM than for
      those with NIDDM. CONCLUSIONS: Recommendations for the care of diabetic
      individuals need to be more widely implemented. Recommendations targeted
      specifically to pediatricians may be necessary.

PMID- 8299441
TI  - Comparison of metoclopramide and erythromycin in the treatment of diabetic
      gastroparesis.
AB  - OBJECTIVE: To compare the effects of erythromycin and metoclopramide on gastric
      emptying and symptoms of gastroparesis in diabetic patients with delayed gastric
      emptying. RESEARCH DESIGN AND METHODS: The study group consisted of 13 patients
      with symptoms of severe gastroparesis and delayed gastric emptying. Gastric
      emptying was evaluated using a radionuclide method, and gastrointestinal symptoms
      were scored. The patients were given either erythromycin (250 mg 3 times/day) or
      metoclopramide (10 mg 3 times/day) in random order for 3 wk, and after a washout
      period of 3 wk they were crossed-over to the other medication for another 3 wk.
      Parameters of gastric emptying were assessed before treatment and after both
      erythromycin and metoclopramide administration. RESULTS: The half-time of gastric
      emptying in diabetic subjects was 110 (77-120) min before treatment. At 60 and 90
      min, the median value of residual isotope activity was 66.5 (55-83.5) and 55% (43
      74.3), respectively. The half-time decreased to 55 min (28.6-115) after 3 wk of
      treatment with erythromycin and percentages of meal retention in the stomach at
      60 and 90 min were 49.9 (38.4-70) and 40.5% (29.7-60), respectively. After taking
      metoclopramide, the median value of half-time was 67 min (15-115) and percentages
      of meal retention at 60 and 90 min were 51 (34.5-93.9) and 42% (24-71.2),
      respectively. When compared with baseline values a significant difference in
      gastric emptying parameters was found after both erythromycin and metoclopramide.
      A significant improvement of the total score for gastrointestinal symptoms was
      observed with both drugs, but this improvement was more pronounced with
      erythromycin. CONCLUSIONS: Erythromycin, a macrolide antibiotic and a motilin
      receptor agonist, appears to stimulate intestinal motility and seems to be an
      alternative agent for the treatment of gastroparesis caused by diabetic autonomic
      neuropathy.

PMID- 8299442
TI  - The child, the adolescent, and the Diabetes Control and Complications Trial.

PMID- 8299443
TI  - Implications of the Diabetes Control and Complications Trial. American Diabetes
      Association.

PMID- 8299444
TI  - The mission of the American Diabetes Association.

PMID- 8299445
TI  - Can a nationwide policy for office-based diabetes education be replicated in the
      United States?

PMID- 8299446
TI  - Assertive outreach follow-up for adolescents with IDDM.

PMID- 8299447
TI  - The prevalence of diabetes and impaired glucose tolerance in a British
      population.

PMID- 8299448
TI  - Exercise and hypoglycemia.

PMID- 8299449
TI  - Blood pressure, insulin, and C-peptide levels in San Luis Valley, Colorado.
AB  - OBJECTIVE: To explore the associations between blood pressure and both fasting
      insulin and C-peptide levels. RESEARCH DESIGN AND METHODS: A cross-sectional
      analysis was conducted of 895 normoglycemic members of a bi-ethnic community in
      Colorado who were selected from a control group recruited for a geographically
      based study of diabetes mellitus prevalence and risk factors. All subjects
      included in this study had normal glucose tolerance as judged by a 75-g oral
      glucose tolerance test interpreted using World Health Organization criteria. None
      of the subjects were taking antihypertensive medication. Multiple linear
      regression analysis was used to examine relationships between fasting insulin and
      C-peptide levels and blood pressure. RESULTS: Among all subjects, diastolic blood
      pressure was found to significantly increase with increasing levels of both
      hormones (insulin coefficient = 0.197, P = 0.013; C-peptide coefficient = 0.0436,
      P = 0.004), whereas systolic blood pressure was significantly related to fasting
      C-peptide level (coefficient = 0.0295, P = 0.050). These relationships were
      similar in magnitude for both Hispanic and non-Hispanic white subjects, but were
      diminished among women and subjects with a higher body mass index. CONCLUSIONS:
      Higher fasting insulin and C-peptide levels are associated with higher blood
      pressure, but these relationships are modified by sex and degree of obesity.

PMID- 8299450
TI  - Prior feeding alters the response to the 50-g glucose challenge test in
      pregnancy. The Staub-Traugott effect revisited.
AB  - OBJECTIVE: To examine the effect of prior meal ingestion on the glucose, insulin,
      and C-peptide response to a 50-g glucose challenge test in the third trimester of
      pregnancy. RESEARCH DESIGN AND METHODS: Ten pregnant women with gestational
      diabetes mellitus and 12 nondiabetic pregnant control subjects matched for age
      and weight underwent a 50-g glucose challenge test on three occasions within a 2
      wk period, in random order. On one occasion the test was administered in the
      fasting state (fasting glucose challenge test), on a second occasion the test was
      administered 1 h after ingestion of a standard mixed meal (1-h postprandial
      study), and on a third occasion the test was administered 2 h after ingestion of
      a standard mixed meal (2-h postprandial study). RESULTS: In the control subjects,
      the plasma glucose level 1 h after ingestion of 50 g of glucose was higher in the
      fasting study (7.8 +/- 0.4 mM, 7 of 12 subjects with glucose > or = 7.8 mM) than
      in the 1-h postprandial study (6.7 +/- 0.3 mM, 3 of 12 subjects with glucose > or
      = 7.8 mM) and the 2-h postprandial study of (6.3 +/- 0.4 mM, 3 of 12 with glucose
      > or = 7.8 mM) (P < 0.01). In the postprandial studies of control subjects,
      insulin and C-peptide levels were higher at the time of ingestion of the 50 g of
      glucose, but the early (1 h) insulin secretory response was less than in the
      fasting study. In the diabetic patients, glucose levels 1 h after 50-g glucose
      ingestion were similar in the fasting study (10.5 +/- 0.4 mM, no subjects with
      glucose value < 7.8 mM) and the 1-h postprandial study (11.0 +/- 0.6 mM, 1
      subject with glucose < 7.8 mM), but was lower in the 2-h postprandial study (9.3
      +/- 0.3 mM, 1 subject with glucose < 7.8 mM) (P < 0.03). In contrast to the
      control subjects, the insulin secretory response to 50 g of oral glucose was
      greater in the two postprandial studies than in the fasting study. CONCLUSIONS:
      We have reached the following conclusions. 1) In nondiabetic gravidas, plasma
      glucose concentrations 1 h after ingestion of a 50-g oral glucose load are higher
      if administered in the fasting state compared with the postprandial state. 2)
      During normal pregnancy the Staub-Traugott Effect, i.e., improved glucose
      disposal after successive glucose load administrations, occurs and appears to be
      caused by mechanisms other than enhanced insulin secretion with successive
      glucose loads. 3) The effect of the prandial state on plasma glucose response to
      the 50-g glucose challenge test used to screen for gestational diabetes mellitus
      may be of sufficient magnitude to significantly alter the operating
      characteristics, i.e., sensitivity and specificity, of this test.

PMID- 8299451
TI  - Reproductive history, glucose tolerance, and NIDDM in Hispanic and non-Hispanic
      white women. The San Luis Valley Diabetes Study.
AB  - OBJECTIVE: To ascertain whether childbearing would decrease oral glucose
      stimulated insulin and C-peptide levels and increase the risk of NIDDM and
      impaired glucose tolerance in a population of Hispanic and non-Hispanic white
      women residing in the San Luis Valley of Colorado. Several investigators have
      related childbearing to subsequent abnormal glucose tolerance. RESEARCH DESIGN
      AND METHODS: In a population-based case-control epidemiological study, diabetic
      patients 20-74 yr of age (n = 196) and randomly sampled control women subjects (n
      = 735) underwent a glucose tolerance test, a physical examination, and an in
      person standardized interview. The relations between the live-birth number and
      fasting and oral glucose stimulated glucose, insulin and C-peptide
      concentrations, and NIDDM and impaired glucose tolerance were estimated using
      linear or logistic regression to adjust for extraneous variables. RESULTS: In
      women selected as control subjects, the live-birth number was related to a
      significant decrease in the sum of 1- and 2-h C-peptide concentrations
      (coefficient = -0.077, P < 0.001) and the logarithm of the sum of 1- and 2-h
      insulin concentrations (coefficient = -0.014, P = 0.02). After adjustment for
      subscapular skin-fold thickness, the relative odds of NIDDM for the live-birth
      number, which was small and of borderline significance, diminished (odds ratio =
      1.04 for one birth, P = 0.18). Findings were similar for impaired glucose
      tolerance. CONCLUSIONS: Childbearing was related to lower C-peptide and insulin
      levels in Hispanic and non-Hispanic women of the San Luis Valley. It had little
      apparent effect on later risk of NIDDM or impaired glucose tolerance.

PMID- 8299452
TI  - Unplanned pregnancies in young women with diabetes. An analysis of psychosocial
      factors.
AB  - OBJECTIVE: To assess psychosocial factors related to preventing birth defects in
      children born to diabetic women. Diabetic women are at high risk for bearing
      children with congenital anomalies associated with teratogenic effects early in
      pregnancy. This study focuses on factors related to the family planning behavior
      of diabetic women. RESEARCH DESIGN AND METHODS: Sixty-six diabetic women were
      included in a 5-yr, prospective, longitudinal study along with 69 phenylketonuric
      women, who also face a high risk of bearing children with birth defects, and 68
      healthy women. Annual interviews and questionnaires were administered. Women who
      did not want a pregnancy completed measures related to contraceptive behavior and
      quality of life. Areas assessed were knowledge, personality, attitudes, and
      social support. RESULTS: Diabetic women were more likely to be sexually active
      than women with phenylketonuria. Use and type of birth control were comparable
      among the groups except that diabetic women used condoms more often. For diabetic
      women, social support and positive attitudes towards birth control were
      associated with consistent birth control use. Of the diabetic women, 23 became
      pregnant, and only 6 (26%) were planned pregnancies. CONCLUSIONS: Birth control
      use by diabetic women needs to be addressed by health professionals. Attitudes
      about birth control of the women and those close to them appear to be important
      factors in consistent birth control use. Suggestions are made for addressing
      these factors.

PMID- 8299453
TI  - IDDM is a risk factor for adolescent psychiatric disorders.
AB  - OBJECTIVE: To determine whether the rate of psychiatric disorders increases in
      children and adolescents with IDDM. RESEARCH DESIGN AND METHODS: The rate of
      psychiatric disorders was assessed by highly structured interviews in a group of
      93 IDDM adolescents 17-19 yr of age and compared with a healthy (nondiabetic) age
      , sex-, and socioeconomic status-matched control group. RESULTS: The rate of
      psychiatric disorders was 33.3% in the diabetic group, more than threefold higher
      than in the control group (9.7%). With regard to the rate of psychiatric
      disorders, no sex-specific differences between the two groups were found. The
      diabetic adolescents suffered from significantly more introversive symptoms than
      their healthy counterparts, especially somatic symptoms, sleeping disturbances,
      compulsions, and depressive moods. In spite of the elevated rate of psychiatric
      disorders, the rates of life events and familial adversities did not increase in
      the diabetic group. CONCLUSIONS: The results support the notion that IDDM
      adolescents should be seen as a high-risk group for psychiatric disorders.

PMID- 8299454
TI  - Incidence of IDDM in Mauritian children and adolescents from 1986 to 1990.
AB  - OBJECTIVE: To document the incidence of IDDM in Mauritian children and
      adolescents 0-19 yr of age from 1986 to 1990. RESEARCH DESIGN AND METHODS: We
      used a population-based register that used pediatricians, physicians,
      nutritionists, and general practitioners as a primary source of retrospective
      case ascertainment. The denominator data were obtained from the Statistics Office
      of the Ministry of Health (Port Louis, Mauritius). RESULTS: In 1990, 37 newly
      diagnosed IDDM cases (22 females and 15 males) were identified between 1986 and
      1990 among the population < or = 19 yr of age. The average incidence density per
      year was 1.9/100,000 people and was slightly higher among girls (2.2/100,000)
      than among boys (1.5/100,000). The average age-standardized incidence density was
      2.1/100,000 people (95% confidence interval 1.5-3.0) among children < or = 14 yr
      of age, 2.5/100,000 people (95% confidence interval 1.5-3.9) among girls, and
      1.8/100,000 people (95% confidence interval 1.0-3.0) among boys. The incidence
      was similarly low in Mauritians of Asian Indian, Chinese, and Creole
      (predominantly African) origin. CONCLUSIONS: The incidence of IDDM in Mauritian
      children and adolescents is among the lowest yet reported. This sharply contrasts
      with the very high risk of NIDDM found among the adult population in this rapidly
      modernizing country.

PMID- 8299455
TI  - Effects of the anatomical region used for insulin injections on glycemia in type
      I diabetes subjects.
AB  - OBJECTIVE: Subcutaneous insulin is absorbed at different rates from different
      anatomical regions, but it is not clear how much the varying rates of absorption
      affect plasma glucose concentrations in diabetic subjects. To address this issue,
      subcutaneous injections of insulin in the abdomen were compared with subcutaneous
      injections of insulin in the thigh. RESEARCH DESIGN AND METHODS: In a crossover
      trial, 22 type I diabetic subjects received, in random order, a test dose of
      regular insulin injected subcutaneously in the abdomen on one morning and in a
      thigh on another morning. The subjects also received, in random order, usual
      morning doses of NPH and regular insulins injected subcutaneously in the abdomen
      on one morning and in a thigh on another morning. The study was performed in the
      University of Minnesota General Clinical Research Center. Main outcome measures
      were plasma glucose and serum free insulin. RESULTS: After injections of regular
      insulin in the abdomen, the peak postprandial increment in plasma glucose was 3.1
      mM or 29% lower (P < 0.001), the peak increment in serum free insulin was 54 pM
      or 38% higher (P = 0.017), and the length of time required to achieve peak serum
      free insulin was significantly shorter than after injections of regular insulin
      in the thigh. After injections of NPH and regular insulins in the abdomen, the
      morning peak increment in plasma glucose was 2.5 mM or 18% lower (P = 0.008) than
      after injections of NPH and regular insulins in a thigh. However, no significant
      difference was observed in the afternoon peak increment in plasma glucose.
      CONCLUSIONS: A subcutaneous injection of regular insulin in the abdomen produced
      a substantially greater reduction in plasma glucose than an injection of regular
      insulin in the thigh. Changing the injection site of regular insulin from the
      abdomen to the thigh had an effect equivalent to reducing the dose administered.
      With injections of NPH and regular insulin in combination, the influence of the
      region used for injection was less but still potentially important.

PMID- 8299456
TI  - Prepregnancy weight and antepartum insulin secretion predict glucose tolerance
      five years after gestational diabetes mellitus.
AB  - OBJECTIVE: To identify phenotypic, genotypic, and metabolic parameters measured
      at the time of antepartum diagnosis of gestational diabetes mellitus that can
      indicate the risk of diabetes mellitus at early postpartum (< or = 6 mo after
      delivery) and at a 5-yr follow-up. RESEARCH DESIGN AND METHODS: The
      recommendations from the National Diabetes Data Group and International Workshop
      Conferences on Gestational Diabetes Mellitus were used for screening, diagnosing,
      and subclassifying gestational diabetes mellitus. National Diabetes Data Group
      criteria were also used for classification of glucose tolerance postpartum.
      Plasma glucose, insulin, and free fatty acids were measured after an overnight
      fast. Plasma glucose and insulin were measured 15, 30, 60, 120, and 180 min after
      the 100-g oral glucose load. Postpartum glucose tolerance was evaluated at 3-6 mo
      (early), 1 yr, and annually thereafter. RESULTS: The 5-yr cumulative incidence of
      diabetes during follow-up after gestational diabetes mellitus was nearly 50%.
      Among those who had diabetes within 5 yr, a history of diabetes in only the
      mother was nearly threefold more common than a history of diabetes in only the
      father (30 vs. 11%, P < 0.01). Those who displayed diabetes at early postpartum
      (< or = 6 mo) testing had significantly higher antepartum glucose levels at 60,
      120, and 180 min compared with those whose early postpartum results were normal.
      They were also relatively insulinopenic at antepartum testing. Their fasting,
      acutely stimulated (15 and 30 min), and integrated 3-h response to oral glucose
      were all significantly lower relative to women who remained normal or had
      impaired glucose tolerance at early postpartum testing. Women who developed
      diabetes between 6 mo and 5 yr postpartum were more obese before the index
      pregnancy, and they had lower fasting, acutely stimulated (15 and 30 min), and
      integrated (1-3 h) insulin levels compared with women who remained normal or
      displayed impaired glucose tolerance at 5 yr postpartum. A multiple logistic
      regression model showed that diabetes present at early postpartum testing was
      independently associated with higher 2-h glucose and lower basal and total
      integrated insulin level. Later (> or = 6 mo-5 yr postpartum) development of
      diabetes was independently associated with prepregnancy weight and impaired
      insulin secretion at diagnosis of gestational diabetes mellitus. CONCLUSIONS:
      Impaired beta-cell function and obesity at diagnosis of GDM were associated with
      the development of diabetes during a 5-yr, follow-up period. Studies designed to
      prevent diabetes in this high-risk group should examine strategies to maintain
      both optimal beta-cell function and maximum insulin sensitivity.

PMID- 8299457
TI  - Alcohol with a meal has no adverse effects on postprandial glucose homeostasis in
      diabetic patients.
AB  - OBJECTIVE: To examine the effect of moderate alcohol intake with a meal on
      glucose homeostasis in diabetic patients. RESEARCH DESIGN AND METHODS: Alcohol (1
      g/kg, an aperitif before, wine during, and a drink after a meal) or an equal
      amount of mineral water was given during a dinner. Blood glucose and insulin
      concentrations were measured before, during, and after the meal until the next
      morning. This study was conducted at the Helsinki University Hospital Metabolic
      Ward and the Finnish Diabetes Association Education Center. The participants in
      the study included 10 type I diabetic patients treated with insulin and 16 type
      II diabetic patients treated with diet alone or with diet and oral drugs. In each
      subject, we examined hypoglycemic episodes or differences in blood glucose or
      serum insulin concentrations between alcohol and the control study. RESULTS: In
      type I diabetic patients, blood glucose and insulin concentrations were virtually
      identical in both studies. In type II diabetic patients, alcohol slightly
      enhanced the meal-induced insulin secretion resulting in lower blood glucose
      concentrations next morning. No hypoglycemic glucose concentrations were observed
      in either group after alcohol ingestion. CONCLUSIONS: Moderate alcohol intake
      with a meal does not lead to hypo- or hyperglycemia in diabetic patients.

PMID- 8299458
TI  - Factors that influence outcome in diabetic subjects with myocardial infarction.
AB  - OBJECTIVE: To compare the outcome of acute myocardial infarction in NIDDM
      patients and nondiabetic control subjects. The relation of glycemic control,
      duration of diabetes, and major diabetic complications to the outcome of acute
      myocardial infarction in diabetic subjects was investigated. RESEARCH DESIGN AND
      METHODS: This was a prospective, hospital-based, case-control study. RESULTS: One
      hundred and ninety-six NIDDM patients and 196 nondiabetic control subjects with
      acute myocardial infarction were entered into the study. 23.5% of diabetic
      subjects and 34.2% of control subjects received thrombolytic therapy (P < 0.05).
      Diabetic subjects showed signs of reperfusion less often than control subjects (P
      < 0.05). Mortality was higher in the diabetic group (17.3 vs. 10.2%, P < 0.05).
      Pump failure (38.3 vs. 16.8%, P < 0.01) and cardiogenic shock (9.7 vs. 3.6%, P <
      0.05) also occurred more frequently in diabetic subjects. Loss of heart rate
      variability was correlated with both pump failure and mortality; proliferative
      retinopathy was correlated with pump failure. Glycemic control and other diabetic
      complications did not correlate with outcome. CONCLUSIONS: Our findings confirm
      the higher mortality and incidence of pump failure in acute myocardial infarction
      with co-morbid diabetes. They suggest that the less frequent use of thrombolytic
      therapy, lower reperfusion rates, and more advanced coronary artery disease might
      be contributory. The presence of autonomic neuropathy and microvascular disease
      probably also contribute to poor outcome; other major diabetic complications and
      diabetic control did not influence outcome.

PMID- 8299459
TI  - Diabetes and associated risk factors among Native Americans.
AB  - OBJECTIVES: To estimate the prevalence of diabetes and related risk factors among
      Native Americans. RESEARCH DESIGN AND METHODS: We used 1988-1989 data from the
      Behavioral Risk Factor Surveillance System to calculate the overall, age-adjusted
      prevalence of diabetes, obesity, sedentary life-style, hypertension, and smoking
      among Native Americans. The SESUDAAN software package was used to derive
      confidence intervals. RESULTS: The prevalence of diabetes was 11.6% among the 768
      Native American Behavioral Risk Factor Surveillance System respondents (95%
      confidence interval 7.8-15.4) and 4.7% among the 121,986 white respondents (95%
      confidence interval 4.6-4.8). The age-adjusted prevalence of diabetes was 2.5
      times higher among Native Americans than among whites. The prevalence of obesity
      was higher among Native Americans (34.4; 95% confidence interval 31.7-37.1) than
      among whites (23.9%; confidence interval 23.7-24.1). The prevalences of sedentary
      lifestyle (58%), hypertension (16%), and smoking (28%) were similar among both
      populations. CONCLUSIONS: The Behavioral Risk Factor Surveillance System may
      prove as a useful tool for surveying Native Americans living on and off
      reservations for inclusion in national estimates of diabetes prevalences.

PMID- 8299460
TI  - Depression and diabetes.

PMID- 8299461
TI  - Type I diabetes and marathon running.

PMID- 8299462
TI  - Hunger. A sensitive but nonspecific symptom of hypoglycemia.

PMID- 8299463
TI  - Combination therapy in NIDDM.

PMID- 8299464
TI  - Diltiazem for tachycardiac orthostatic hypotension in NIDDM.

PMID- 8299465
TI  - Human insulin. A decade of experience and future developments.

PMID- 8299466
TI  - Human insulin after 10 years.

PMID- 8299467
TI  - Growth and the child with diabetes mellitus.

PMID- 8299468
TI  - Sweet success with diabetes. The development of insulin therapy and glycemic
      control for pregnancy.

PMID- 8299469
TI  - Future developments in insulin delivery systems.

PMID- 8299470
TI  - Research, development, production, and safety of biosynthetic human insulin.
AB  - This paper provides some historical aspects on the research and development of
      Humulin (rDNA origin), the first human health-care product derived from rDNA
      technology more than a decade ago. Also referred to as biosynthetic human
      insulin, Humulin is currently produced via the human proinsulin route, using an
      Escherichia coli fermentation process. The authenticity, high purity, and safety
      of BHI has been investigated and verified by a complex battery of analytical and
      physicochemical methods. The daily treatment of more than two million diabetic
      patients worldwide with this rDNA human insulin not only demonstrates the value
      of rDNA technology in providing an important medical product, it is assurance
      that diabetic patients will have unlimited supplies of this vital hormone as well
      as potential analogue refinements.

PMID- 8299471
TI  - Insulin therapy in the last decade. A pediatric perspective.

PMID- 8299472
TI  - Immunogenicity and allergenic potential of animal and human insulins.
AB  - Immunological complications of insulin therapy have been evident since animal
      insulins became available for the treatment of diabetes mellitus in 1922. Insulin
      allergy has been particularly common, with local symptoms still occurring in
      approximately 5% of all patients. Insulin antibodies of high titers were observed
      in many patients treated with early insulin preparations containing proinsulin, C
      peptide, and other peptide contaminants. Immunoglobulin G-insulin antibodies of
      very high levels can lead to immune-mediated insulin resistance, which is now
      extremely rare because of the widespread use of highly purified porcine insulin
      and human insulin preparations. Lipoatrophy, which was reported in 10-55% of
      patients treated with nonpurified bovine/porcine insulin preparations, has almost
      disappeared in patients since the advent of exclusive human insulin treatment. In
      view of the wide spectrum of immune-mediated complications of insulin therapy,
      much attention has been directed to the reduced immunogenicity and allergenicity
      of highly purified porcine insulins and the more recently available recombinant
      and semisynthetic human insulin preparations. Insulin antibodies of the
      immunoglobulin G and immunoglobulin E type can develop, however, in very low
      titers in patients treated exclusively with human insulin. Frequency and levels
      of immunoglobulin G insulin antibodies are identical in patients treated either
      with biosynthetic or semisynthetic human insulin preparations. Allergic symptoms
      to human insulin are now found in < 1% of de novo-treated patients, but still may
      occur when human insulin is used in the insulin-allergic patient. In summary,
      immunological complications of insulin therapy have decreased significantly
      during the last two decades and are now predominantly observed in patients with
      interrupted insulin therapy.

PMID- 8299473
TI  - New directions in drug development: mixtures, analogues, and modeling.
AB  - Success in modern medical research is achieved when basic and clinical
      information about a given disorder converges, either intentionally or
      fortuitously, with the availability of technology or other means to design and
      apply interventions for the disorder in question. A prime example is the
      discovery of insulin and its replacement in patients with IDDM in 1923. Seven
      decades later, the focus of diabetes management is on improvement in metabolic
      control to forestall the chronic complications of the disease and improve the
      quality of life of patients with the disease. Metabolic control is being
      addressed through the development of insulin analogues using sophisticated
      techniques to understand the chemistry of insulin and to modify it using rDNA
      technology. The objective of these efforts is to simulate normal insulin
      secretion with subcutaneously injected agonists. Quality-of-life needs are being
      addressed with delivery devices, insulin mixtures, and insulin analogues.
      Although none of these improvements parallel the discovery of insulin, they do
      provide an optimistic outlook for patients with diabetes mellitus.

PMID- 8299474
TI  - Insulin regimens and strategies for IDDM.

PMID- 8299475
TI  - Insulin therapy in type II diabetes.
AB  - Administration of exogenous insulin can ameliorate metabolic abnormalities in
      type II diabetes: It compensates for reduced endogenous insulin secretion,
      reduces excessive hepatic glucose production, and stimulates glucose uptake,
      enhancing both glucose oxidation and storage in the muscle tissue. In addition,
      insulin therapy has anti-atherogenic effects on serum lipid profile. The main
      concerns of insulin therapy are weight gain, hyperinsulinemia, hypoglycemia, and
      possibly sodium and fluid retention. Although studies in vitro and in
      experimental animals suggest that hyperinsulinemia may accelerate
      atherosclerosis, these data are not substantiated in patients with type II
      diabetes. Insulin therapy in type II diabetes patients can be used either
      temporarily when insulin requirements are increased (e.g., surgery, infection,
      pregnancy), or in the long-term when endogenous insulin secretion is vanishing or
      hyperglycemia does not respond to other therapy. Whether insulin should be used
      as a primary therapy in addition to diet and exercise in some patients has not
      been examined. The decision regarding the beginning of insulin therapy and
      targets should be established individually, taking into account factors such as
      age, other diseases, or life expectancy. Various regimens can be used, including
      evening insulin alone or in combination with oral agents, multiple injections,
      use of premixed insulins (short-plus intermediate-acting insulin in various
      combinations). Continuous subcutaneous insulin infusion also has been used.
      Comparative data between the regimens are scant, but a few studies suggest that
      no major differences occur between the regimens, with regard to glycemic control
      or hypoglycemic complications. In the future, insulin therapy in type II diabetes
      may become more common, particularly among patients with the autoimmune type of
      the disease.

PMID- 8299476
TI  - The history of insulin.

PMID- 8299477
TI  - Hypoglycemia unawareness in IDDM.
AB  - Hypoglycemia unawareness--loss of the neurogenic (autonomic) warning symptoms of
      developing hypoglycemia--is one of three hypoglycemia-associated clinical
      syndromes that exemplify hypoglycemia-associated autonomic failure in IDDM.
      Reduced awareness of developing hypoglycemia (an elevated glycemic threshold for
      symptoms) is a feature not only of hypoglycemia unawareness but also of the
      syndromes of defective glucose counterregulation, elevated glycemic thresholds
      for symptoms, and activation of glucose counterregulatory systems during
      effective intensive therapy. These syndromes are major risk factors for severe
      iatrogenic hypoglycemia in individuals with IDDM. Their pathogenesis is unknown
      and likely multifactorial. Recent antecedent iatrogenic hypoglycemia may be one
      factor, perhaps a major factor, that, by reducing both the symptoms of and
      defenses against developing hypoglycemia, results in recurrent iatrogenic
      hypoglycemia, thus creating a vicious cycle. On the other hand, treatment with
      human compared with animal insulin does not appear to be an important factor.

PMID- 8299478
TI  - Physiological responses to hypoglycemia. Counterregulation and cognitive
      function.

PMID- 8299479
TI  - Hyperinsulinemia--how innocent a bystander?
AB  - Hyperinsulinemia is very much in the spotlight. Debate rages as to its
      significance and role in the etiology not only of NIDDM, but also other
      morphological and metabolic risk factors for atherosclerotic cardiovascular
      disease, including upper-body obesity, dyslipidemia, hypertension, and
      hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in
      these disorders but it is far from conclusive except for the fact that
      hyperinsulinemia and insulin resistance may be present many years before the
      onset of impaired glucose tolerance and NIDDM, and clearly play a role in their
      etiology. The thrifty genotype hypothesis provides a plausible basis for a better
      understanding of how hyperinsulinemia and insulin resistance could lead to
      glucose intolerance and atherosclerotic cardiovascular disease, but the detailed
      biochemical mechanisms remain elusive. A role for increased sympathetic nervous
      system activity, resulting from hypothalamic stimulation as a primary event
      causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The
      current focus on hyperinsulinemia also has resulted in closer examination of the
      therapy of diabetes and hypertension, emphasizing the need to avoid
      hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk
      of atherosclerotic cardiovascular disease and hypertension. There is still a
      paucity of epidemiological data to support a role for hyperinsulinemia in the
      etiology of hypertension. However, clinical practice already is being influenced
      by the fact that ACE inhibitors have been shown to reduce insulin resistance in
      clinical research studies. The research reviewed here, particularly that relating
      to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors,
      has opened new vistas for the treatment and prevention of NIDDM and
      atherosclerotic cardiovascular disease. Appropriate exercise clearly is
      associated with improved insulin sensitivity, modification of CVD risk factors,
      and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the
      field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance
      can be detected in children, adolescents, and young adults. NIDDM can be
      prevented, but clearly, intervention needs to commence in childhood, and
      intensive risk factor intervention in subjects with NIDDM can reduce the risk of
      atherosclerotic cardiovascular disease. It seems paradoxical that prevention of
      NIDDM and atherosclerotic cardiovascular disease are now possible even though the
      biochemical and molecular basis of these disorders is not fully understood.

PMID- 8299480
TI  - Nocturnal blood glucose control in type I diabetes mellitus.
AB  - A major problem in replacing insulin in type I diabetes mellitus is that
      currently no depot preparation exists that is capable of mimicking the background
      insulin secretion of the healthy pancreas. Because all of the currently available
      intermediate- or long-acting insulin preparations have a peaked-action profile,
      excess insulin action at midnight and insulin waning at dawn occur whenever such
      an insulin preparation is given at supper time. If the target fasting plasma
      glucose is the ambitious near-normoglycemia of intensive insulin therapy,
      intermediate-acting insulin at suppertime easily results in hypoglycemia in the
      early evening hours and hyperglycemia in the fasting state. The problems of
      overnight glycemia in type I diabetes are further complicated by the dawn
      phenomenon and the Somogyi phenomenon. The dawn phenomenon is the combination of
      an initial decrease in insulin requirements between approximately 2400 and
      approximately 0300, followed by an increase in the insulin needs between
      approximately 0500 and approximately 0800. The dawn phenomenon is the result of
      changes in hepatic (and extrahepatic) insulin sensitivity, which are best
      attributed to nocturnal growth hormone secretion. The dawn phenomenon is a day-to
      day reproducible event that occurs in nearly all diabetic patients. Its
      contribution to fasting hyperglycemia correlates with diabetes duration
      (inversely) and the HbA1c percentage (directly). Overall, it is estimated that
      the specific contribution of the dawn phenomenon to fasting hyperglycemia is
      approximately 2 mM (approximately 35 mg/dl), but it may be much greater because
      of the warning of the depot-insulin preparation injected the previous evening.
      The Somogyi phenomenon, strictly speaking, refers to fasting hyperglycemia that
      occurs after inducement of nocturnal hypoglycemia by regular insulin. Because the
      present therapeutic regimens of NPH/Lente insulin given at suppertime cause
      overnight hyperinsulinemia, excessive fasting hyperglycemia rarely follows
      nocturnal hypoglycemia, except when excessive glucose is ingested to correct
      hypoglycemia. However, nocturnal hypoglycemia may easily deteriorate glycemic
      control later in the day, because it induces prolonged posthypoglycemic insulin
      resistance, which results in postbreakfast and late-morning hyperglycemia. With
      nocturnal insulin therapy, it is important to consider the problems of insulin
      pharmacokinetics, the dawn phenomenon, and the Somogyi phenomenon to prevent both
      nocturnal hypoglycemia and excessive fasting hyperglycemia.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8299481
TI  - Gestational diabetes.

PMID- 8299483
TI  - Insulin resistance, hyperinsulinemia and diabetes--contribution of benfluorex.
      Prague, 11 September 1992. Symposium proceedings.

PMID- 8299482
TI  - Clinical pharmacology of human insulin.
AB  - Nowadays, human insulin is used daily by millions of diabetic patients. The
      biological effect of human insulin is comparable to that of porcine insulin.
      However, after subcutaneous injection, pharmacological and clinical studies
      showed pharmacokinetic and pharmacodynamic differences between human and animal
      insulins. Human insulin tends to have faster absorption and shorter duration of
      action compared with animal insulin. These differences are more pronounced and
      can be of clinical relevance with intermediate- and long-acting insulin
      preparations. Optimal metabolic control can be achieved with either human or
      highly purified animal insulin preparations, provided appropriate insulin
      replacement strategies are used.

PMID- 8299484
TI  - Epidemiological data on hyperinsulinaemia and vascular disease.

PMID- 8299485
TI  - Mechanism(s) of the blood glucose lowering action of benfluorex.
AB  - Benfluorex is a hypolipidaemic agent with biguanide-like properties. To evaluate
      its blood glucose lowering action, a single-blind study protocol was designed.
      Two groups of seven type II (non-insulin-dependent) diabetic patients matched for
      age (50 +/- 4 vs. 53 +/- 1 years), sex, body mass index (27.8 +/- 0.6 vs. 26.5 +/
      0.7 kg/m2), and duration of diabetes were studied before and after 1 month of
      treatment with benfluorex 150 mg tid (= tres in die = three times a day), PO (=
      per os = by mouth) or a placebo, respectively. All patients had previously been
      treated by diet alone. In all patients, parameters of glucose and lipid
      metabolism were obtained. Insulin sensitivity was assessed by means of a
      euglycaemic (5.1 +/- 0.1 mM) hyperinsulinaemic (516 +/- 28 pM) clamp performed in
      combination with [3(-3)H]glucose infusion and indirect calorimetry. In no case
      was there a significant change in body mass index (27.6 +/- 0.5 vs. 26.4 +/- 0.7
      kg/m2). After 1 month of treatment, fasting plasma glucose (6.8 +/- 0.2 vs. 8.1
      +/- 0.6 mM) and HbA1C (glycated haemoglobin; 6.5 +/- 0.2 vs. 8.0 +/- 0.7%) were
      lower in the benfluorex group than in the placebo-treated patients (both p <
      0.05). No change was observed in hepatic glucose production (HGP) (13.5 +/- 1.4
      vs. 13.9 +/- 1.1 mumol/min per kg), the basal rate of glucose, and lipid
      oxidation and non-oxidative glucose metabolism, or in plasma triglyceride and
      total cholesterol concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299486
TI  - Benfluorex decreases insulin resistance and improves lipid profiles in obese type
      2 diabetic patients.
AB  - Benfluorex hydrochloride has known lipid- and glucose-lowering effects. We
      evaluated the change in lipids, fasting glucose, and insulin sensitivity in ten
      obese type 2 diabetic patients after treatment with benfluorex or a placebo for 2
      weeks using a double-blind, cross-over design. Insulin sensitivity was measured
      using the euglycaemic-hyperinsulinaemic glucose clamp technique at two insulin
      infusion rates for 2 h each: 0.05 U/kg per h (clamp 1) and 0.10 U/kg per h (clamp
      2). Mean fasting glucose decreased from 13.1 +/- 1.1 to 10.2 +/- 0.9 mmol/l after
      benfluorex (p < 0.001) and rose from 11.9 +/- 0.9 to 13.3 +/- 1.0 mmol/l after
      the placebo (p = 0.028). Insulin did not change significantly. Glucose uptake
      (GU) as a parameter for insulin sensitivity was compared for treatment with
      benfluorex versus the placebo. Total GU during clamp 1 was 643.4 +/- 323.8 mmol
      after benfluorex and 250.1 +/- 193.3 mmol after the placebo (p = 0.035), and
      during clamp 2, 2490.7 +/- 490.5 mmol after benfluorex and 1544.3 +/- 693.9 mmol
      after the placebo (p = 0.018). The dynamic analysis on the last 30 min of clamp 2
      showed a significant difference in glucose infusion rate (GIR) profile, with mean
      levels yielding 5.36 mmol/kg per min after benfluorex and 3.87 mmol/kg per min
      after the placebo (p = 0.018); there were no differences in plasma insulin
      concentrations or plasma glucose levels. It is concluded that in this short-term
      study benfluorex increases insulin sensitivity in obese type 2 diabetic
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299487
TI  - Anti-hyperglycaemic mechanisms of benfluorex in type II diabetes mellitus.

PMID- 8299488
TI  - Islet defects and insulin resistance in models of obese non-insulin-dependent
      diabetes.

PMID- 8299489
TI  - Role of insulin resistance in the pathophysiology of non-insulin dependent
      diabetes mellitus.

PMID- 8299490
TI  - Mechanisms for the effects of benfluorex on the obese-diabetic-dyslipidemic
      syndrome.

PMID- 8299491
TI  - Effect of benfluorex on insulin secretion and insulin action in streptozotocin
      diabetic rats.
AB  - We have examined the effect of chronic (20 days) oral administration of
      benfluorex (35 mg/kg) in a rat model of non-insulin-dependent diabetes mellitus
      (NIDDM), as induced by injection of streptozotocin 5 days after birth and
      characterized by frank hyperglycaemia, hypoinsulinaemia, and hepatic and
      peripheral insulin resistance. In the benfluorex-treated diabetic rats, basal
      plasma glucose levels were decreased (7.9 +/- 0.2 mM as compared with 17.2 +/-
      1.1 mM in the pair-fed untreated diabetic and 6.7 +/- 0.2 mM in the benfluorex
      treated non-diabetic rats) while the basal and the glucose-stimulated (IVGTT)
      plasma insulin levels were not improved. The lack of improvement of glucose
      induced insulin release after benfluorex treatment was confirmed under in vitro
      conditions (perfused pancreas). In the benfluorex-treated diabetic rats, basal
      glucose production and overall glucose utilization were normalized. Following
      hyperinsulinaemia (euglycaemic clamp), glucose production was normally suppressed
      while overall glucose utilization was not significantly improved. Since
      benfluorex exerts a predominant action on the liver in the present rat model of
      diabetes, and since increased basal hepatic glucose output is a major metabolic
      abnormality and is responsible for much of the elevated fasting blood glucose
      levels in NIDDM, the use of such a compound in NIDDM may be potentially relevant.

PMID- 8299492
TI  - Effects of benfluorex on in vivo patterns of insulin resistance induced by diets
      rich in fat or fructose.

PMID- 8299494
TI  - An update on OSHA.

PMID- 8299493
TI  - Effect of chronic benfluorex treatment on interaction of insulin 123I with liver
      receptors in fa/fa Zucker rats.

PMID- 8299495
TI  - Keeping it clean in the dental office. Guidelines help prevent cross
      contamination.

PMID- 8299496
TI  - Reimplanting an avulsed tooth.

PMID- 8299497
TI  - All for one and one for all.

PMID- 8299499
TI  - Common sense equipment care.

PMID- 8299498
TI  - Whiteners.

PMID- 8299500
TI  - Managing your insurance claims.

PMID- 8299501
TI  - How to match the real thing. Tips on choosing shades for artificial teeth.

PMID- 8299502
TI  - Wolfram syndrome: a clinical study of two cases.
AB  - Two unrelated patients with two different images of Wolfram (or 'DIDMOAD')
      syndrome are presented: a 19-year old woman suffering from all the important
      features of this syndrome, and a 38-year old man showing two major
      characteristics but several minor abnormalities. This syndrome should be
      considered in young diabetic patients with unexplained visual loss or with
      polyuria and polydipsia in the presence of adequate blood sugar control. An early
      diagnosis is important to prevent unnecessary diagnostic investigations.

PMID- 8299503
TI  - Clinical and metabolic factors associated with the blood retinal barrier
      permeability in insulin dependent diabetes mellitus without retinopathy.
AB  - The authors assessed a study pointing out the relationship between the
      permeability of Blood Retinal Barrier (BRB), using vitreous fluorophotometry, and
      several risk clinical and laboratory data in Insulin Dependent Diabetes Mellitus
      (IDDM). Eighty eyes of 40 IDDM patients were evaluated. Their mean age was 14.8
      +/- 3.2 years. Twenty healthy volunteers served as control group (mean age 15.3
      +/- 3.2 years). Preexisting diabetic retinopathy was dismissed after funduscopy
      and fluorescein angiography. The studied risk factors were: age, duration of
      diabetes, HLA antigens, blood pressure, cholesterol and triglycerides levels,
      glycosylated hemoglobin, insulin dose/kg body weight and fructosamine. Vitreous
      and lens fluorophotometry was performed in both groups (VPRt). The mean VPRt in
      IDDM patients was 3.56 +/- 1.47 x 10(-6) min-1. In healthy subjects it was 2.53
      +/- 0.55 x 10(-6) min-1, establishing a significant difference (p < 0.01). We
      found a statistically significant correlation between VPRt and duration of
      diabetes, insulin dose/kg body weight and HbAlc. No correlation was found between
      VPRt and the rest of parameters. We conclude that vitreous fluorophotometry is a
      valid method to measure BRB; and the three factors mentioned above are related to
      the BRB permeability.

PMID- 8299504
TI  - Contrast sensitivity peripheral to an absolute central scotoma in age-related
      macular degeneration and the influence of a yellow or an orange filter.
AB  - Contrast sensitivity for static and dynamic gratings was determined in 17
      patients with age-related macular degeneration (AMD) and an absolute central
      scotoma. Using electronic and computerized equipment, we established contrast
      sensitivity peripheral to the scotoma at spatial frequencies of 0.5, 1.0 and 2.0
      cycles/degree. We found that mean contrast sensitivity was significantly (p <
      0.001) lower than that of a control group at a comparable eccentricity, and that
      interindividual variations were large. Furthermore, we investigated the influence
      of a yellow and an orange filter on contrast sensitivity peripheral to such an
      absolute central scotoma in AMD. The results showed significant (p < 0.01-0.05)
      improvements in contrast sensitivity at certain spatial frequencies only, i.e.,
      for the yellow filter at 2.0 c/deg and for the orange filter at 0.5 and 1.0
      c/deg, and only with dynamic presentation. No objective improvement in visual
      acuity could be demonstrated when using filters. Thus, our findings do not
      unequivocally support the regular prescription of such filters in order to
      improve contrast vision in AMD with an absolute central scotoma.

PMID- 8299505
TI  - Ocular toxocariasis in children and youth.
AB  - The number of infections with larvae of the Toxocara canis worm has been
      continuously increasing in the Polish population, and the diagnosis and treatment
      of this disease is difficult. The authors describe 81 cases of eye infection in
      children and youth at the age of 3 to 18 years. The lesions in 94 eyes were
      observed for 0.5 to 11 years. In all patients the diagnosis was confirmed by
      ELISA test. In the clinical picture various forms of uveitis and granuloma of the
      eye fundus were found. The treatment consisted in general and topical application
      of antihelmintics, antibiotics and corticosteroids. In 23 eyes photocoagulation,
      in 11 cryopexy, and in 3 vitrectomy was performed. Clinical improvement was
      observed in 50 eyes, stabilization of the lesions in 41 eyes, and deterioration
      in the remaining 3 eyes. The authors conclude that the best results are obtained
      through conservative treatment combined with photocoagulation and cryopexy.

PMID- 8299506
TI  - Non specific orbital inflammatory diseases.
AB  - The understanding of 'pseudotumors' has significantly changed with the advent of
      modern imaging techniques by which the tissues affected in the orbit can be
      identified, and nonspecific orbital inflammatory disease is classified according
      to the tissue involved. Twenty cases of nonspecific orbital inflammatory diseases
      were treated between July 1987 and September 1991. Eight patients had myositis, 6
      had diffuse disease, 2 each had dacryoadenitis, periscleritis and perineuritis.
      Involvement of all four recti in one patient and isolated superior rectus and
      superior oblique each in 2 others are the unusual forms of myositis. Perineuritis
      presented as diffuse thickening of the optic nerve on CT scan with disc edema and
      normal vision in both patients with external ophthalmoplegia in one of them. All
      patients responded to oral steroids while the patient with myositis of all four
      recti required radiotherapy in addition. This series documents the spectrum of
      clinical presentation, diagnosis and management of nonspecific orbital
      inflammatory disease.

PMID- 8299507
TI  - An unusual fundus finding in a patient with optic nerve pit syndrome.
AB  - In a study of 12 patients with optic nerve pits, a female patient presented an
      unusual fundus finding in which there were many flat grey-white lesions in both
      eyes. These lesions covered a large area of the fundus and extended from the
      posterior pole to the periphery. There was an optic pit in the right eye and an
      inferior coloboma in the left eye. The visual acuities and the clinical findings
      remained unchanged over the follow-up period of 2 years. Fluorescein angiographic
      and electrophysiological examinations suggested that these lesions were probably
      located at or beneath the retinal pigment epithelium.

PMID- 8299508
TI  - Two therapeutic concepts in intermittent divergent squint.
AB  - Several therapeutic concepts are in favour of the treatment of intermittent
      exotropia. The presented paper will try to answer the question, whether this
      leads to different results, by the review of the 1989 and 1990 cases of two
      centres. In the Munich Right Isar Eye Hospital (Centre II) during this period 72
      patients (already published data) were treated by recession and resection eye
      muscle surgery against intermittent exotropia or decompensating exophoria. The
      111 compared patients of the Department of Orthoptics and Pleoptics at the
      University Eye Hospital Kiel (Centre I), were mostly treated with bimedial
      resection procedures. Another difference: diagnostic occlusion and prism
      correction were done in the Munich patients. There is major evidence that there
      are two widely different clinical pictures incorporated in the diagnostic frame
      of the so-called 'Intermittent Exotropia'. In a third prospective group of
      patients (10/91-3/92), therefore, the prism-acceptance was evaluated.

PMID- 8299509
TI  - [Definition of "salt sensitivity"].
AB  - To examine how the term "salt sensitivity" has heretofore been defined, two
      medical data bases, DIMDI and MEDLINE were searched. 32 clinical studies,
      published between 1978-1992 and using the terms salt-, sodium- or sodium chloride
      sensitive or sensitivity were found and analysed. Salt sensitivity was
      experimentally determined and applied in quite varied ways to normotensive and
      hypertensive persons. There were three types of studies: in type 1 (n = 15), a
      phase of low sodium intake was followed by one with a high intake; in type 2 (n =
      8), a phase of high or "normal" sodium intake was followed by a low intake one;
      in type 3 (n = 9), there was a randomized sequence of differing sodium intake
      phases, in some cases with cross-over. It is concluded from these studies that
      there is insufficient evidence to distinguish between salt sensitive and salt
      insensitive subjects. Consequently scientific discussion of this question should
      not lead to hypertensives being discouraged from reducing their salt intake.

PMID- 8299510
TI  - [Therapeutic bilateral renal artery embolization in the nephrotic syndrome].
AB  - Amyloidosis with renal involvement was diagnosed in a 52-year-old man with
      Crohn's disease for 15 years. A severe nephrotic syndrome developed (proteinuria
      40 g daily) with oedema and arterial hypotension (80/60 mm Hg). As adequate
      substitution treatment was not possible an attempt at medical renal ablation was
      made with a combination of captopril (25 mg daily), frusemide (80 mg daily) and
      indomethacin (200 mg daily). The proteinuria decreased to 18 g daily, but serum
      creatinine concentration rose to 5.8 mg/dl so that chronic haemodialysis had to
      be undertaken. Yet the patient's clinical state hardly improved and, because of
      his poor general condition, bilateral nephrectomy was contraindicated. In
      consequence bilateral catheter embolization of the renal arteries was performed.
      The urinary protein loss fell at once to 0.5 g daily. Serum protein rose from 3.1
      g/dl under substitution to 5.7 g/dl without. During the following six months,
      while on chronic haemodialysis, the nephrotic syndrome did not recur. However,
      cardiac involvement in the amyloidosis was demonstrated so that the prognosis is
      poor. Permanent bilateral embolization of the renal arteries is a feasible method
      of managing a treatment-resistant nephrotic syndrome in selected patients.

PMID- 8299512
TI  - [Acute ulcer hemorrhage. Evaluation of endoscopic therapy methods].

PMID- 8299511
TI  - [Enterocolic fistula due to foreign body perforation].
AB  - A 26-year-old man reported diarrhoea, abdominal pain and weight loss (16 kg in 3
      weeks). Ultrasonography and computed tomography showed a 5 x 5 cm abnormal
      rosette-shaped mass with surrounding infiltration in the area of the left colic
      flexure. Laboratory tests indicated a florid inflammation. Coloscopy and double
      contrast radiology of the colon revealed a fistula at the junction between
      sigmoid and descending colon. At laparotomy a large tumorous mass was found (18 x
      15 x 10 cm), which was removed completely by partial resection of small intestine
      and colon. Histological examination revealed occlusion of an intestinal loop by a
      plastic foreign body (probably the cap of a household cleaner bottle). The
      patient would not provide any explanation of the circumstances leading to its
      ingestion.

PMID- 8299513
TI  - [Familial glucocorticoid resistance as the differential diagnosis of
      hypercortisolism. Clinical and molecular genetic aspects].

PMID- 8299514
TI  - [Osteoporosis in men?].

PMID- 8299515
TI  - [Angina pectoris after traumatic spinal body fracture and leg vein thrombosis].

PMID- 8299516
TI  - [Annual test for occult blood in stool and intestinal cancer mortality].

PMID- 8299517
TI  - [An isolated tuberculoma in the left ventricle].
AB  - In the course of 8 weeks, a 62-year-old woman with chronic bronchitis developed
      increasing dyspnoea on effort and reduced well-being. The chest radiograph
      revealed a round focus, 2 x 3 cm, in the region of the left ventricle which, from
      the results of echocardiography and left-heart catheterization, suggested myxoma.
      At open-heart surgery under extracorporeal circulation an encapsulated tumour was
      found on the mural leaflet of the mitral valve, directly caudal of the
      atrioventricular plane. On opening, the capsule contained dough- or paste-like,
      yellowish-white substance with scattered polygonal granules, typical of a
      tuberculoma. The entire contents and capsule were excised. Immediately after
      operation tuberculostatic treatment was initiated (three times daily ethambutol,
      400 mg, and once daily rifampicin, 600 mg, and isoniazid, 300 mg), even though
      acid-fast rods were not demonstrated histologically and by culture. Polymerase
      chain reaction, however, established the presence of Mycobacterium tuberculosis
      in the resected material. There was no evidence of florid tuberculosis in the
      subsequent course.

PMID- 8299518
TI  - [Diagnosis and therapy of pancreatic cancer].

PMID- 8299519
TI  - [The loin pain and hematuria syndrome].

PMID- 8299520
TI  - [Privatization of hospital radiology departments. The verdict of the Social
      Court, Frankfurt, 28.4.1993].

PMID- 8299521
TI  - [Liability for the substitution of drugs in the hospital].

PMID- 8299522
TI  - [Blind needle biopsy of the liver].

PMID- 8299523
TI  - [Hyponatremia in cardiac insufficiency].

PMID- 8299524
TI  - [Coronary sclerosis in primary hyperparathyroidism].

PMID- 8299525
TI  - [The anti-angina effect of spinal cord stimulation in angina pectoris induced by
      pacing].

PMID- 8299526
TI  - [Long-term therapy of bronchial asthma with glucocorticoids].

PMID- 8299527
TI  - [The effect of angiotensin-converting enzyme inhibitors on proteinuria in chronic
      glomerulonephritis].
AB  - The effect of two angiotensin-converting enzyme (ACE) inhibitors, lisinopril and
      captopril, on proteinuria and renal haemodynamics was investigated in 11
      hypertensives (9 men, 2 women; mean age 46 +/- 16 years) with proteinuria (> 1.5
      g/24 h) due to chronic glomerulonephritis and impaired renal function (glomerular
      filtration rate < 75 ml/min). In a randomized and double-blind cross-over trial
      the patients received, each time for six weeks, either lisinopril (5 mg/d,
      sometimes increased to 10 mg/d after 3 weeks) or captopril (twice daily 12.5 mg,
      sometimes increased to twice 25 mg after 3 weeks). Initially and between the
      individual treatment phases they were on a placebo phase for 4 weeks. The
      following were measured: protein excretion, including fractional clearance of
      albumin and IgG, plasma-renin activity and renal haemodynamics. Protein excretion
      was not significantly reduced by either drug (placebo: 7.1 +/- 4.0 g/d;
      lisinopril: 5.1 +/- 2.8 g/d; captopril: 5.4 +/- 3.0 g/d). Albumin excretion and
      fractional albumin clearance were significantly decreased only by lisinopril (P <
      0.05), not by captopril. Plasma-renin activity was increased more by lisinopril
      than captopril (Placebo: 1.0 +/- 0.9 ng/ml.h; lisinopril: 5.2 +/- 2.8 ng/ml.h [P
      < 0.05]; captopril: 1.8 +/- 1.3 ng/ml.h [P < 0.05]). The renal haemodynamics was
      only slightly influenced by either drug, but captopril significantly decreased
      the filtration fraction in the presence of chronic glomerulonephritis and renal
      failure. - Resulting from their influence on the renin-angiotensin-aldosterone
      system, ACE inhibitors have, in addition to their known action on renal
      haemodynamics, an independent effect on the loading barrier of the basal membrane
      of the kidney.

PMID- 8299528
TI  - [Long term follow up of lymphoplasmocytoid immunocytoma].
AB  - Two women with lymphoplasmocytoid immunocytoma (Waldenstrom's macroglobulinaemia)
      have been followed up, one for 23 years and the other for 18. In the first
      patient the disease presented at the age of 40 years with lassitude and
      paraesthesiae. Investigation revealed monoclonal IgM-lambda with a serum IgM of
      3350 mg/dl and marrow infiltration by lymphoplasmocytoid cells. As there were no
      symptoms, apart from migraine attacks which responded well to plasmapherese, and
      because haemopoiesis was unaffected and the lymph nodes were not enlarged, no
      cytostatic has so far been given. The proportion of lymphoplasmoid cells in the
      marrow is at present 50%. In the second patient the disease presented at the age
      of 33 with involvement of stomach and lung, and a conglomerate tumour in the
      upper abdomen. The serum showed an M-gradient together with raised IgM (3056
      mg/dl). Chemotherapy (COPP protocol) and local irradiation of the stomach
      achieved full remission. At intervals of several years there have been
      histologically confirmed recurrences in the hypophyarynx, ovaries, hilum of left
      lung and, most recently, in the upper abdomen once more. These have been
      successfully treated by resection and local radiotherapy (hypopharynx), operation
      followed by chemotherapy (COP protocol) (ovaries, upper abdomen) or by
      radiotherapy alone (hilum of lung-50 Gy).

PMID- 8299529
TI  - Nd: YAG pulsed laser: a successful tool to desensitize hypersensitive prepared
      abutment teeth in fixed prosthodontics.
AB  - Dentinal hypersensitivity follows several therapeutic dental procedures as well
      as occurring de novo. Pain being an unpleasant sensation, originates from dentine
      which has a rich supply of myelinated nerve ending. There are several theories
      that explain the mechanism of pain of dentinal origin. Thermal, tactile and
      chemical stimuli when applied to affected teeth might result in brief mild
      discomfort to prolonged severe pain. There are several theories regarding
      dentinal hypersensitivity.

PMID- 8299530
TI  - Light microscopic and ultrastructural study of thinned discal areas in patients
      with temporomandibular joint internal derangement.
AB  - It is generally believed that pathological destruction of the articular tissue
      occurs whenever articular remodeling does not maintain a balance between its
      structure and function. Remodeling is a natural cellular response contingent on
      the capability and availability of viable cells. Remodeling maintains the
      anatomic integrity of individual cells. Remodeling maintains the anatomic
      integrity of individual joint components that sustain the wear and tear occurring
      normally in the joint while accomplishing work. If the mechanical forces are
      within the physiological tolerance of the articular structures, cellular repair
      will keep up with destruction to protect the joint from deformation. It is
      hypothesized that the TMJ disc lacks the reserve remodeling capacity that
      characterizes the condyle and articular eminence. The lack of blood supply to the
      disc proper renders it dependent on nutrient diffusion from an intact synovial
      film. Many factors may change both the composition and the continuity of this
      nutritional source. Therefore, the synovial fluid may be the solitary source of
      nutrition for cellular healing and remodeling of the avascular part of the joint.
      Carlsson et al. felt that longstanding increased compressive forces on the disc
      may lead to cell necrosis and matrix degradation culminating in thinning of the
      disc and subsequent perforation.

PMID- 8299531
TI  - The effect of mandibular overdenture to manage trauma to anterior maxillary
      residual ridge.
AB  - Residual alveolar ridge changes brought on by bone loss has always been one of
      the great problems related to denture prosthesis. The changes beneath denture
      bases has been investigated and the agreement on individual difference on the
      rate of bone resorption has been proven. Clinical experience and studies gave
      great knowledge of the prosthetic factors which influence bone resorption. It has
      been proved that excessive pressure, and shearing forces are the main causes of
      ridge changes. Very common is the problem associated with patient having only
      natural mandibular anterior teeth occluded with complete upper denture. The
      anterior maxillary region is the weakest area in the upper arch to resist stress
      when the lower natural anterior teeth occlude anterior to the basal support;
      trauma is inevitable.

PMID- 8299532
TI  - Mesiodistal tooth width. A comparison between Saudi males and females. Part 1.
AB  - The aim of this study is to investigate whether there is a significant sex
      difference or not in the mesiodistal tooth width between Saudi males and females.
      720 teeth were measured from a pre-treatment orthodontic study casts with equal
      distribution of the two sexes. The subjects were aged 13 to 20 years. An
      electronic digital caliper was used for the measurements. For the statistical
      analysis the Student's t-test was used. The result of this investigation showed
      that the canines in both jaws exhibited a significant sex differences while the
      other teeth did not. Hence, this study confirms results obtained by other
      investigators and emphasize the fact that mesiodistal tooth width is an important
      factor in the assessment of crowding, spacing and orthodontic treatment planning.

PMID- 8299533
TI  - Mesiodistal tooth width in a Saudi population sample comparing right and left
      sides. Part 2.
AB  - The objective of the present study was to investigate whether there was a
      significant difference or not in mesiodistal tooth width between the right and
      left sides in a Saudi sample. The measurements were obtained from 720 teeth of
      pretreatment orthodontic study casts. The results showed no significant
      statistical difference between right and left sides, which in agreement with
      literature. Thus, measurement of one side could be regarded as truly
      representative when the corresponding measurement on the other side was
      unobtainable.

PMID- 8299534
TI  - An investigation on the shear bond strength of three dentine adhesives.
AB  - The aim of this investigation was to compare the shear bond strengths of three
      dentine adhesives tested using an Instron Universal Testing machine at a
      crosshead speed of 0.5 mm/min. Sixty human molar teeth were used and divided into
      3 equal groups where the occlusal surfaces were ground and adhesives were applied
      overlaid by composite material. Samples were fixed to the Universal Testing
      machine. Results were recorded in kg/cm2 and converted into MPa units then
      tabulated and statistically analyzed. Duncan's multiple range statistic test at p
      < 0.05 showed no statistically significant difference between the shear bond
      strength values of Scotchbond 2 and Amalgambond; whereas the shear bond strength
      values of Scotchbond 2 and Amalgambond were significantly higher than those of
      Gluma. Scanning electron microscopic examinations at X10 and X2500 magnifications
      showed a dominant adhesive pattern of failure in the samples treated with Gluma,
      and a mixture of cohesive and adhesive-cohesive patterns of failures in the
      samples treated with Scotchbond 2 and cohesive patterns of failures in the
      samples treated with Scotchbond 2 and Amalgambond.

PMID- 8299535
TI  - Clinical follow-up of TMJ disc perforations treated with bilaminar synovial flap
      repair.
AB  - This report presents the follow up results on a group of 36 patients treated for
      T.M.J disc perforations. Postoperative follow-up was performed by two oral and
      maxillofacial surgeons. Worling independently. The synovial membrane flap proved
      to be a clinically successful treatment modality in treating T.M.J. disc
      perforations.

PMID- 8299536
TI  - Dentine roughness after different surface treatments.
AB  - Surface roughness is one of the most influential criteria affecting the
      durability and strength of the adhesive restorative materials to the dentine.
      This study was carried out to investigate the roughness of the dentine surface
      after some of the modalities proposed for its treatment prior to application of
      the DBA. Dentine surface roughness of the sixty teeth divided into 12 groups were
      tested where the dentine surfaces were denuded and were brought to a similar 600
      grit surface roughness then different treatments were carried out using H2O2, CO2
      gas laser at 30 and 48 J/cm2 energy densities, EDTA and polyacrylic acid
      treatments. The dentine surface roughness was determined using a profilometer and
      the results were digitized and plotted using an AUTO-CAD software and Rolland
      plotter to compare the effects of the different treatments on the dentine surface
      roughness of the tested samples. Results revealed that the laser treatment left
      smooth dentine surface and added further evidences to the simplicity and
      reliability of the conventional use of EDTA and the polyacrylic acid according to
      the type of adhesive to be used.

PMID- 8299537
TI  - Impacted cuspids in a Saudi population: prevalence, etiology and complications.
AB  - The prevalence, etiology and related complications of impacted maxillary and
      mandibular cuspids were studied among a convenient sample of 4,898 Saudi patients
      aged 13 years and older. Results indicate that 175 patients (3.6%) out of a
      sample had at least one impacted cuspid. Most (22.9%) possessed multiple
      involvement. Female patients were found to be more concerned about the problem (p
      < .001). The maxillary arches were usually affected more frequently. The most
      common location of maxillary cuspid impactions was palatal and the lingually
      located impaction in the mandible was found to be very rare. In most of the
      subjects the lack of arch space was the main etiological factor. Cuspid
      impactions were found to be occasionally associated with various unfavorable
      sequelae.

PMID- 8299538
TI  - Evaluation of a new glass ionomer cement "visible light cured" as a core buildup
      under a cast restoration.
AB  - Proper restoration of endodontically treated teeth is a frequent challenge to
      many clinicians. The majority of restorations are using various types of vertical
      support that can be placed in teeth, these include different prefabricated post
      systems as well as cast posts and cores. Less emphasis, unfortunately, has been
      placed on the materials utilized for final build up. Unless the tooth being
      treated undergoes minimal loss of tooth structure some from of augmentation will
      be necessary to increase the tooth strength and provide adequate support and
      retention for the final cast restoration. It is generally accepted that the ideal
      methods of corono-radicular buildup for nonvital teeth is a properly fabricated
      cast post and core.

PMID- 8299539
TI  - Serum and salivary IgG and IgA response to radiation therapy.
AB  - Patients undergoing radiotherapy for malignant tumors of the head and neck
      invariably develop extensive oral and dental diseases particularly when the major
      salivary glands are within the radiation fields. Unless the patient receives a
      strict oral hygiene home care and the teeth are protected by topical application
      of fluoride gel, caries or gingival disease onset inevitably follows radiation
      induced xerostomia is. The importance of saliva as a controlling factor in the
      development of oral diseases is underscored by the dramatic increase in dental
      decay and gingival diseases that inevitably follows the surgical extirpation of
      the major salivary glands in animals and the onset of xerostomia in man.

PMID- 8299540
TI  - [Recovery from depression].

PMID- 8299541
TI  - [Recovery from depression. 8th international thematic meeting. Paris, 27 November
      1992. Proceedings].

PMID- 8299542
TI  - [Clinical criteria in evaluating recovery from depression. Methodologic aspects].
AB  - According to recent European epidemiological studies, the lifetime prevalence of
      major depression ranges between 16 and 20%. Information concerning the natural
      course of depressive illness remain limited. Longitudinal studies of depressed
      patients are impeded by the inconsistencies of the labelling of change points in
      the course of illness (remission, recovery, relapse, recurrence...) and of
      criteria used to define each of them. Recently, definitions of these terms have
      been proposed but still need to be clinically validated. Internationally accepted
      definitions are particularly necessary in order to assess the efficacy of
      antidepressants at 3 levels: during the acute treatment of an episode, for
      maintenance treatment (recovery from the complete length of an episode) and for
      prophylactic treatment (reduction of the risk of future episodes).

PMID- 8299543
TI  - Depression in older people. Some criteria for effective treatment.
AB  - Depression at a level requiring clinical attention affects 12-15% of those over
      65 in the community. Only a small minority are in contact with specialist mental
      health services, the majority of these depressed older patients will require
      detection and treatment in primary care. Although the symptoms of depression,
      once elicited, are similar to those of younger patients, initial presentation in
      older people can be misleading, and the onset and outcome of depression in this
      age group is closely linked with the state of current physical health and social
      adversity. Pharmacotherapy is effective for treatment, but both the family doctor
      and older patient may be reluctant to consider and persist with antidepressant
      medication. A controlled study is described which aims to improve the management
      of older patients in primary care by evaluating the role of a nurse acting as
      case manager to work in conjunction with family doctors and community agencies to
      implement a plan of treatment for depression. Preliminary results indicate that
      the nurse was effective through her personal work with depressed older patients,
      despite the fact that the recommended introduction of antidepressant medication
      was often not possible.

PMID- 8299544
TI  - [Treatment of a refractory depressive episode].
AB  - In treating refractory depression, we have, firstly, to search for some factors,
      known to be associated with resistance, like somatic illnesses or drugs which
      induce depression. In a second time, it is necessary to distinguish refractory
      depression from insufficiently treated depression. For this purpose: does the
      treatment fit to the subtype of depression to be treated? Is the dosage of
      antidepressant sufficient? is the duration of treatment trial long enough? Some
      strategies can be used to treat resistant depressive patients. Mono Amine Oxidase
      Inhibitors (MAOIs) seem to be sometimes very efficient in the treatment of
      refractory depressives. In some cases, it is necessary to prescribe high dosages
      of such drugs or to use them in association with tricyclic antidepressants. It
      must be emphasized that such associations are sometimes dangerous and must be
      used cautiously. Selective Serotonin Reuptake Inhibitors (SSRIs) seem to be
      characterized by a different spectrum of effects than tricyclics. This
      specificity could be useful in treating refractory depression; ECT are often
      efficient in such patients and must be done if antidepressants fall to improve
      the disorder. Adjunction of lithium to antidepressant regimen is efficient in
      many cases and well documented since a few years. This association is efficacious
      in almost 30% of refractory depressive disorders. In some cases, adjunctive
      lithium leeds to improvement of depressive symptoms very quickly, in 2 or 3 days.
      In other cases, onset of improvement occurs only after the usual time of 2 to 3
      weeks. The adjunction of triiodothyronine (T3) to antidepressants is sometimes
      efficacious and raises some questions about the thyroid axis function in
      depressives.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299545
TI  - [Choice of antidepressant treatment after a major depressive episode].
AB  - The choice of an antidepressant is not necessary during the initial phase of only
      treatment (acute treatment), it can be reviewed after one or two months
      (continuation treatment) and a prophylactic treatment may be discussed after a 6
      months period (long-term maintenance treatment). Many reasons explain the need to
      readjust the dosage of antidepressant treatment or to change it: the nature and
      the gravity of the depression, the family and personal history of affective
      disorders, the level of side effects and above all the quality of the recovery.
      Thus the modification of a treatment can be considered according to 4 methods:
      modification of the psychotropes associated to antidepressant treatment,
      association of a second antidepressant medication, change of antidepressant
      medication, institution of a prophylactic treatment. A special aspect concerns
      the decision and the choice of the antidepressant treatment after recovery by
      E.C.T. Two types of treatment can be considered: most often a maintenance
      treatment of antidepressant medication is suggested. Prolongation of ECT may be
      justified for consolidation: 6 or 8 sessions after recovery, or for prevention of
      relapse: session every 3-4 weeks after recovery, and for a period of 2-3 years.

PMID- 8299546
TI  - [Evolution of depression in the child and adolescent].
AB  - Outcome of depressive disorder in adolescents is now better known. Despite
      methodological differences between studies there is an agreement to emphasize
      frequency of relapse and recurrence in the follow-up (50 to 60%). Others
      modalities have also been described, anxiety disorders seemed to be the more
      frequent. For some authors, affective disorder in adolescents could presage manic
      depressive illness. Psychosocial functioning after the follow-up seems to be
      impaired as well as in professional, relational, or social fields. These data
      suggest a clear distinction between affective states in adolescents and symptoms
      related to psychological transformations of adolescence. We have conducted a
      follow-up study with adolescents hospitalized in the child and adolescent
      psychiatric department of R. Debre hospital, for major depressive episode (MDE)
      or dysthymic disorder (DD). On the 122 patients meeting initially inclusion
      criteria, 75 have been evaluated after one year follow-up at least. Duration of
      the follow-up was on average 4 years. 44 met initially DSM III and DSM III-R
      criteria for MDE and 31 for DD. Rating has been done during a phone interview
      with a standardized questionnaire. We did use criteria defined by Prien et al.
      (1984) for relapse, recurrence and remission. Our results showed a good short
      term outcome in both groups (72.7% remission in MDE and 80.6% in DD). Relapse
      rate was superior in the first group. At the end of the follow-up, cumulative
      probability of recurrence was 52.9% in MDE group and 35.7% in DD group. Chronic
      evolution was more frequent in TD group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299547
TI  - [Impact of life events in the course of depression].
AB  - The impact of recent life events in the provoking of depressive episodes is well
      established, but their weight in the course of depression has not been frequently
      studied. Some data can nevertheless be extracted from published research: First,
      life events occurring before the beginning of the episode are predicative neither
      of the response to treatment, nor of the long-term evolution of major depressive
      episodes. Reactional depression seem to be more sensitive to placebo than non
      reactional depressions, and, minor reactional depression could have a better
      spontaneous course. Second, stressful life events and long-lasting difficulties
      contemporary with the episode are some of the more important clues for
      durability, and sometimes chronicity, of depressive symptoms. Some of those
      events are independent (not controlled by the subject), but some are also
      dependent, produced by the subject and his depressive state. On the other hand,
      certain types of life events (like "neutralizing events" or "fresh start events")
      and the stress reduction of long-lasting difficulties, seem to favour remission
      of minor depressions. Third, weight of life events in relapse and recurrence of
      depression is significant, but seems to be less important than in the release of
      first depressive episodes. The interaction between life events and the genesis of
      depression can be observed from sociological, psychological or biological point
      of view. Future analysis should be based on the distinction between vulnerability
      factors, which modulate the impact of life events, and susceptibility factors,
      which can have a sensibilization role.

PMID- 8299548
TI  - [Impact of personality factors in depression].
AB  - Patients meeting criteria for borderline personality disorder are heterogeneous.
      Our studies suggest that at least two sub-types exist which benefit from specific
      treatments. Data will be presented which suggests that some patients who meet
      borderline criteria and have atypical depression (patients meeting DSM III-R
      criteria for major depression or dysthymia reactive wills mood and any vegetative
      atypical symptoms, i.e. overeating, oversleeping, rejection sensitivity, leaden
      paralysis) clearly benefit from treatment with antidepressant medication.
      Although some patients with atypical depression who meet borderline criteria will
      improve with tricyclic therapy, a significantly greater proportion will improve
      with the monoamine oxidase inhibitor (MAOI) phenelzine if they suffer from
      atypical depression. The validity of emotionally unstable character disorder
      (EUCD) will also be examined. Patients with this disorder frequently meet
      criteria for borderline character disorder. The validity of this sub-group is
      supported by the presence of neurological soft signs, their negative response to
      anti-depressants, and their positive response to chlorpromazine and lithium.

PMID- 8299549
TI  - Mixed anxiety depression. For and against.
AB  - The subject of mixed anxiety depression has been the topic of a somewhat confused
      discussion. At one point, it was held that anxiety and depression were both
      manifestations of an underlying affective disorder, but systematic work by Martin
      Roth and others clearly demonstrated that anxiety disorders could be separated
      from depressive disorders via a multivariate scale. Interestingly, spontaneous
      panic attacks were among the highest loading items on this scale. Nonetheless, it
      was plain that many patients were simultaneously anxious and depressed. Interest
      then grew in understanding the evolution of these syndromes over time. In
      general, anxiety syndromes antecede depressive syndromes, although there are many
      exceptions. For instance, some people only develop panic attacks when in the
      midst of a depressive episode. To attempt to understand these complexities,
      detailed family studies have been attempted with often contradictory results. We
      shall present family study data indicating that patients with comorbid panic
      disorder and depression have different familial patterns from those with panic
      disorder alone. In addition, a practical question is whether there exist
      patients, primarily in private settings, who present with symptoms of anxiety and
      depression but do not meet full criteria for any of the currently defined
      syndromes. Such patients are often referred to as subsyndromal or subthreshold
      patients. Epidemiological data indicates that such patients exist and that their
      symptomatology is associated with social and functional impairment. Recently the
      DSM IV field trial has specifically addressed this issue by clinical
      investigations of primary care and psychiatric facilities. These results will be
      reported.

PMID- 8299550
TI  - [Famous depressed persons who have influenced the history of their country].

PMID- 8299551
TI  - A critical role for interleukin-1 (IL-1) and the type 1 IL-1 receptor in
      blastocyst implantation.

PMID- 8299552
TI  - Embryonic implantation in mice is blocked by interleukin-1 receptor antagonist.
AB  - We have investigated the relevance of interleukin-1 receptor type I (IL-1R tI) in
      the implantation process in vivo in a murine model. Indirect immunofluorescence
      experiments demonstrate that IL-1R tI is located in mouse endometrial lumenal
      epithelium with increased intensity in the periimplantation period, whereas IL-1
      beta staining is located in the mouse placenta. PMSG/human CG (hCG)-stimulated
      and mated 12-week-old B6C3F-1 female mice were randomly allocated to three
      groups: A, control noninjected; B, buffer-injected animals; and C, animals
      injected ip with 20 micrograms recombinant human IL-1 receptor antagonist (rhIL
      1ra) every 12 h beginning on pregnancy day 3. Injections were continued until day
      9, and animals were killed 12 h after the last injection. Pregnancy rates in the
      three groups were: noninjected, 58.8% (10 of 17); buffer-injected, 73.7% (14 of
      19); rhIL-1ra-injected, 6.7% (1 of 15), P = 0.0001155, Fisher exact test. To rule
      out the possibility that pregnancy failure was due to an embryotoxic effect of
      rhIL-1ra, 2-cell mouse embryos (n = 276) were flushed from the same group of
      animals used for in vivo experiments and cultured with increasing concentrations
      of rhIL-1ra: 0 microgram/ml (n = 91), 1 microgram/ml (n = 36), 50 micrograms/ml
      (n = 36), 100 micrograms/ml (n = 52), and 200 micrograms/ml (n = 61) rhIL-1ra.
      The percentages of 2-cell mouse embryos reaching the blastocyst stage after 72 h
      in culture were 85.7%, 91.6%, 94.4%, 96%, and 85.2%, respectively. We further
      cultured these blastocysts for 5 days on fibronectin-coated plates with or
      without 200 micrograms/ml rhIL-1ra. In both groups, hatching, attachment to
      fibronectin, outgrowth, and migration were documented to be similar. Furthermore,
      our longitudinal morphological study of embryonic implantation in control and
      rhIL-1ra-injected mice shows that the blockade of IL-1R tI interferes with the
      attachment of mouse blastocysts to maternal endometrium in vivo. In summary, we
      demonstrate that blockade of maternal endometrial IL-1R tI with IL-1ra prevents
      implantation in the mouse by interfering with embryonic attachment, without
      adverse effects on blastocyst formation, hatching, fibronectin attachment,
      outgrowth, and migration in vitro.

PMID- 8299553
TI  - Evidence that phosphorylation events participate in thyroid hormone action.
AB  - Using both a protein phosphatase inhibitor, okadaic acid (OA), and a protein
      kinase inhibitor, H7, to modify phosphorylation events in the cell, we
      investigated the effects of these agents on transcriptional activation via
      exogenous rat thyroid hormone receptor (TR) isoforms in transiently transfected
      cells and endogenous TRs. CV-1 cells were transiently cotransfected with
      expression plasmids encoding either the rat TR alpha 1 or TR beta 1, and
      luciferase reporter plasmids containing either the synthetic DR4 or the chick
      lysozyme F2 thyroid hormone response elements (TREs). For both receptor isoforms,
      there was an enhancement of transcriptional activity after incubation with 5 nM
      T3 for 24 h compared to hypothyroid levels. There was little change in
      transcriptional activation in the presence of 25 nM OA alone; however, for both
      TR isoforms and both TREs studied, OA augmented the stimulatory effects of T3.
      For the F2 TRE, transcriptional activation via TR alpha 1 increased from 19- to
      35-fold, and that via TR beta 1 increased from 6- to 10-fold in the presence of
      T3 and OA compared to that with T3 alone. Similar results were found for the DR4
      TRE. OA enhanced transcriptional activation by T3 in a dose-dependent manner.
      Increasing concentrations of OA (0, 5, 25, and 50 nM) further increased relative
      luciferase activity from 11-fold in the absence of OA to 45-fold in the presence
      of 50 nM OA. The protein kinase inhibitor, H7, caused no change in the
      transcriptional activity of the reporter plasmids via TR alpha 1 in the absence
      of T3, but completely blocked transcriptional activation by T3 for both the DR4
      and the F2 TREs. H7 also blocked stimulation of endogenous GH and inhibition of
      endogenous TR beta 2 mRNAs by T3 in GH3 cells. These results indicate that
      phosphorylation events in the cell play an important role in transcriptional
      activation via both TR isoforms.

PMID- 8299554
TI  - A recombinant extracellular domain of the thyrotropin (TSH) receptor binds TSH in
      the absence of membranes.
AB  - We produced large quantities of the extracellular domain of the human TSH
      receptor (ETSHR) using the baculovirus expression system. Insect cells containing
      the ETSHR protein were sequentially extracted using lysis, nuclease, and high
      salt buffers to enrich for recombinant protein. The ETSHR protein was purified to
      homogeneity on a C4 reverse phase semipreparative column using HPLC. The
      recombinant protein was identified as ETSHR by immunoreactivity with antibodies
      prepared against TSHR-derived synthetic peptides. The identity of the ETSHR was
      further confirmed by amino acid compositional analyses, which agreed with the
      amino acid composition predicted from reported cDNA sequence analyses. Protein
      sequence analyses confirmed that the first 26 amino acids of the N-terminal
      region and the C-terminal amino acid were identical to the predicted amino acid
      sequence. The purified ETSHR was refolded in the presence of 1.5 M guanidine-HCl
      and 1 mM each of cystine and cysteine. [125I] TSH bound to the refolded ETSHR in
      vitro in a dose-dependent manner and was specifically blocked by unlabeled TSH,
      but not by LH or FSH. It was notable that a membrane requirement was not
      essential for TSH to bind to ETSHR.

PMID- 8299555
TI  - The effect of time of day on levels of hypothalamic proopiomelanocortin primary
      transcript, processing intermediate and messenger ribonucleic acid in proestrous
      and estrous rats.
AB  - Several lines of evidence from different laboratories suggest that hypothalamic
      beta-endorphinergic activity decreases around the time of initiation of the LH
      surge and may increase on estrus to extinguish the expression of the daily
      neuronal signal for the surge. In several hormone systems, factors that stimulate
      or suppress hormone release also stimulate or repress transcription of the
      hormone gene and translation of the messenger RNA encoding the hormone.
      Therefore, information about neurohormone activity may be inferred from data on
      changes in the levels of RNA species encoding these neurohormones. We used a
      solution hybridization/RNase protection assay to test the hypotheses that 1) the
      abundance of primary transcript of the hypothalamic POMC gene decreases at the
      time of initiation of the proestrous LH surge and 2) levels of POMC primary
      transcript (and by inference, levels of beta-endorphin neuronal activity and
      secretion) increase on estrus. 96 rats exhibiting at least two consecutive 4-day
      estrous cycles were killed at either 0600 or 1300 h on proestrus and estrus.
      Dissections of the medial basal hypothalamus were pooled into 4 samples at each
      time-point (6 rats per sample) and RNA was extracted from nuclear and cytoplasmic
      fractions separately. We measured levels of POMC primary transcript, processing
      intermediate and fully spliced mRNA in the nuclear fractions and POMC mRNA in
      cytoplasmic fractions. Compared to 0600 h, levels of POMC primary transcript
      decreased significantly during the afternoons of both proestrus and estrus (P <
      0.05). Levels of nuclear processing intermediate RNA and cytoplasmic mRNA
      followed the same trend but the afternoon declines did not reach statistical
      significance. We conclude from these data that the afternoon decline in POMC gene
      expression is not unique to the day of proestrus and we speculate that an
      afternoon decline in beta-endorphinergic neuronal activity may instead be a
      component of the daily signal for the LH surge.

PMID- 8299556
TI  - Relationship between thyroid hormone transport and neutral amino acid transport
      in JAR human choriocarcinoma cells.
AB  - The relationship between the transport of the thyroid hormone T3 and the
      transport of neutral amino acids was investigated in JAR human placental
      choriocarcinoma cells. The uptake of leucine, mediated by the amino acid
      transport system L, was inhibited by T3 and T4, and the nature of inhibition was
      competitive. Uptake of T3 into the cells was predominantly Na+ independent, and
      so was that of leucine. However, although an acidic extracellular pH stimulated
      leucine uptake, the uptake of T3 remained unaffected. In addition, leucine failed
      to inhibit T3 uptake. The aromatic amino acids phenylalanine and tryptophan were
      found to inhibit the uptake of T3, but these two amino acids were transported
      into the cells predominantly via system L. The amino acid transport system T,
      which is specific for aromatic amino acids, was not detectable in these cells.
      Treatment of the cells with the calmodulin antagonist CGS 9343 B stimulated the
      uptake of leucine and tryptophan, but inhibited the uptake of T3. Kinetic
      analysis of T3 uptake revealed the presence of a single saturable system for this
      hormone in these cells, and the Michaelis-Menten constant for this system was
      0.77 +/- 0.06 microM. Metabolic poisons that interfere with the cellular
      generation of ATP had no effect on the uptake of T3. It is concluded that in
      placental choriocarcinoma cells, 1) T3 and T4 are high affinity competitive
      inhibitors of the amino acid transport system L, 2) uptake of T3 occurs via a
      specific Na(+)-independent, energy-independent, and saturable mechanism that is
      unrelated to the amino acid transport systems L and T, 3) the aromatic amino
      acids phenylalanine and tryptophan interact, although weakly, with the T3 uptake
      system, and 4) calmodulin-dependent processes participate in the regulation of
      the T3 uptake system.

PMID- 8299557
TI  - Calcitonin stimulates growth of human prostate cancer cells through receptor
      mediated increase in cyclic adenosine 3',5'-monophosphates and cytoplasmic Ca2+
      transients.
AB  - Our recent study has shown that a calcitonin (CT)-like immunoreactive
      substance(s) is secreted by cultured prostate cells, and secretion of this
      material is significantly higher in malignant than in benign prostate cells. To
      test the hypothesis that prostatic CT may serve as a paracrine/neuroendocrine
      factor, the present study investigated for the presence of CT receptors in the
      prostate gland. Signal transduction mechanisms activated by CT were examined, and
      the study also tested its effects on prostate cell proliferation, as assessed by
      [3H]thymidine incorporation. The results show that high affinity binding sites
      for [125I]salmon CT were present in plasma membrane fractions of human prostate
      tissue specimens and the prostate cancer LnCaP cell line. The maximal binding for
      CT receptors was 564 +/- 163 fmol/mg protein, and the apparent dissociation
      constant (Kd) was 2.89 +/- 0.58 nM. CT induced a dose-dependent increase in cAMP
      generation in LnCaP cells. The effect of CT on cytoplasmic Ca2+ transients of
      LnCaP cells was examined by videofluoromicroscopy. CT (100 nM) induced a rapid
      and sharp increase in cytoplasmic Ca2+ concentrations in LnCaP cells. The CT
      induced increase in cytoplasmic Ca2+ transients appeared to be biphasic (spike
      and plateau), and this increase was 4- to 10-fold during the initial phase. The
      profile of this response is characteristic of the activated Ca2+/phospholipid
      second messenger system. CT also caused a dose-dependent increase in
      [3H]thymidine incorporation by LnCaP cells. These results suggest that a locally
      secreted CT-like peptide(s) induces mitogenic responses in prostate cancer cells.
      This action seems to be mediated through activation of signaling mechanisms,
      leading to the accumulation of two different second messengers, cAMP and calcium.
      Activation of dual second messenger systems by CT receptors suggests that the
      peptide hormone may play an important role in rapidly growing cell populations
      during the process of tumor formation.

PMID- 8299558
TI  - Luminal bile salts and neurotensin release in the isolated vascularly perfused
      rat jejuno-ileum.
AB  - Bile salts in the distal small intestine are strong stimulants of neurotensin
      (NT) release, but the underlying mechanisms are not known. They were investigated
      using an isolated vascularly perfused rat jejuno-ileum preparation. Luminal
      administration of crude ox bile extract (0.25-1.5%, wt/vol) produced a dose
      dependent release of NT-like immunoreactivity (NT-LI), with a maximal effect
      after infusion of 1% bile extract (500% of basal). Pretreatment of the 1% bile
      extract with the bile salt-sequestering resin cholestyramine (2%, wt/vol)
      abolished NT-LI release. Taurocholate (TC), the major bile salt in rats, dose
      dependently increased the release of NT. The maximal secretion of NT-LI was
      observed after infusion of 20 mM TC (400% of basal). Taurodeoxycholate (20 mM)
      was as potent as TC in stimulating NT-LI release, but the threshold concentration
      of taurodeoxycholate for NT-LI secretion was lower than that of TC. Glycocholate
      and cholate were 2- to 3-fold less potent than TC in releasing NT-LI over the
      concentration range 5-20 mM. Luminal infusion of oleic acid (sodium salt; 100 mM)
      increased by 100% the level of NT-LI in the portal effluent, whereas 20 mM oleate
      had no effect. In contrast, the micellar form of oleic acid (20 and 100 mM) in
      bile extract (1%) or TC (20 mM) dose dependently reduced the release of NT-LI
      induced by bile extract or TC alone. Neither intraarterial tetrodotoxin (10(-6)
      M), EGTA (2 mM), verapamil (5 x 10(-5) M), nor atropine (10(-5) M) had any effect
      on TC-induced NT-LI release. These results show that the tauro-conjugated forms
      of cholic and deoxycholic acid are strong stimulants of NT-LI release. The N-cell
      response is blunted when bile salts are complexed in the lumen by oleic acid.
      Finally, bile salt-induced NT-LI release is not mediated by intramural nerves and
      is not dependent on the activation of calcium channels.

PMID- 8299559
TI  - Pioglitazone inhibits the diabetogenic action of growth hormone, but not its
      ability to promote growth.
AB  - Analogs of thiazolidinedione improve the responsiveness of insulin-resistant
      animals to insulin. One such analog, pioglitazone (5-(4-[2-(5-ethyl-2
      pyridinyl)ethoxy]benzyl)thiazolidine-2,4-dione hydrochloride), when fed to
      insulin-resistant animals such as the obese (ob/ob) mouse, reduces blood glucose
      and lipids and also lowers the plasma insulin level. Because GH can produce
      insulin resistance in humans and animals such as the ob/ob mouse, the present
      study was conducted to determine whether feeding pioglitazone can 1) inhibit the
      ability of GH to induce enhanced insulin resistance in obese mice, 2) ameliorate
      or reverse GH-induced insulin resistance once it has been induced in ob/ob mice,
      and 3) alter the ability of GH to promote growth in hypophysectomized rats.
      Female ob/ob mice were fed a control diet or a diet containing pioglitazone (20
      mg/kg animal.day) for 4 days. During the last 3 days of the feeding period, the
      mice also received a daily sc injection of either saline or 200 micrograms S
      carboxymethylated human GH (RCM-hGH), which is a GH derivative having mainly
      diabetogenic activity. In control-fed mice, RCM-hGH increased blood glucose and
      plasma insulin levels, which is an expected response to GH-induced insulin
      resistance. By contrast, the ability of RCM-hGH to increase blood glucose and
      plasma insulin levels was totally blocked in pioglitazone-fed mice. To determine
      whether pioglitazone can ameliorate GH-induced insulin resistance once it has
      been established, ob/ob mice were treated sc with either saline or 200 micrograms
      RCM-hGH for 3 days. Half of the saline-treated and half of the hormone-treated
      mice were then fed pioglitazone, whereas the remaining animals were continued on
      the control diet. After 48 h on the diets, the blood glucose and plasma insulin
      levels of the RCM-hGH treated mice fed the control diet remained elevated with
      respect to those in the saline-treated controls. On the other hand, the blood
      glucose and plasma insulin levels of the RCM-hGH treated mice fed pioglitazone
      were markedly reduced compared to those of the RCM-hGH-treated control-fed
      animals. Thus, these results suggest that pioglitazone can ameliorate GH-induced
      insulin resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8299560
TI  - 17 beta-estradiol and parathyroid hormone potentiate each other's stimulatory
      effects on alkaline phosphatase activity in SaOS-2 cells in a differentiation
      dependent manner.
AB  - We studied the effects of 17 beta-estradiol (E2) and PTH on alkaline phosphatase
      activity in SaOS-2 cells that had been passaged and grown continually in the
      presence (SaOS + Dex) or absence (SaOS - Dex) of 10(-8) M dexamethasone (Dex). We
      showed that the more differentiated SaOS + Dex cells had higher alkaline
      phosphatase activity and PTH-responsive adenylate cyclase than the less
      differentiated SaOS - Dex cells. In SaOS - Dex cells, E2 or PTH (1 x 10(-11)-1 x
      10(-6) M) had no effect on alkaline phosphatase activity. On the other hand, in
      SaOS + Dex cells, PTH and E2 each had small but very significant stimulatory
      effects on alkaline phosphatase activity. The combined effects of PTH and E2
      resulted in potentiation which was dose dependent for PTH and E2. 17 alpha
      estradiol and tamoxifen (1 x 10(-11)-1 x 10(-6) M) had no effect on PTH
      stimulated alkaline phosphatase activity in SaOS + Dex cells, but the latter
      inhibited the E2 effect, clearly demonstrating its specificity. In conclusion, we
      have shown that in more differentiated osteoblastic cells, E2 and PTH have
      interactive effects on alkaline phosphatase activity.

PMID- 8299561
TI  - Seasonal and tissue-specific regulation of canary androgen receptor messenger
      ribonucleic acid.
AB  - Natural seasonal fluctuations in androgen levels appear to cause changes in
      physiology and reproductive behavior, such as singing, in canaries. Little is
      known, however, about the cellular mechanisms underlying these changes. Because
      androgens act principally through nuclear receptors in other species, we have
      isolated and sequenced a cDNA likely to encode the canary androgen receptor and
      used this cDNA to examine the regulation of AR mRNA levels in the testis, kidney,
      and liver of the canary. The sequence corresponds to most of the coding portion
      of seven of the eight exons found in the homologous mammalian gene, including the
      domains that bind to DNA and androgen and affect transcription. Its mRNA is
      approximately 8 kilobases in length and is encoded by a single gene. In the
      testis, the transcript is expressed specifically in the Sertoli cells. The
      androgen receptor antagonist flutamide represses AR mRNA levels in kidney, but
      induces them in liver, indicating that androgen regulates its receptor, but does
      so in a tissue-specific manner, as is seen for the estrogen receptor in rodents.
      In addition, there are natural seasonal fluctuations in AR mRNA levels in testis
      and liver correlated with seasonal differences in the levels of circulating
      androgens. This is the first evidence of natural feedback regulation of AR mRNA
      levels.

PMID- 8299562
TI  - The positive effect of parathyroid hormone on femoral neck bone strength in
      ovariectomized rats is more pronounced than that of estrogen or bisphosphonates.
AB  - This study elucidates the effect of PTH, estrogen, and the bisphosphonate
      Risedronate (NE-58095) on femoral neck bone strength in ovariectomized (OVX) rats
      aged 90 days at the beginning of the investigation. Furthermore, the effects of
      these monotherapies were compared with those of concurrent treatment with PTH
      plus estrogen or PTH plus bisphosphonate. Four weeks after surgery the rats were
      randomized into a sham-operated vehicle-treated group, an OVX vehicle-treated
      group, and the various treatment groups and followed for 5 and 15 weeks. The
      proximal one-third of the left femur was then subjected to geometrical
      measurements and biomechanical testing. Neither ovariectomy nor the different
      treatment regimens influenced femoral neck geometry. OVX rats exhibited a
      decrease in femoral neck bone strength compared with control rats. This was most
      evident after 5 weeks. Treatment of OVX rats with Risedronate or estrogen alone
      tended to increase bone strength to control level, though these findings were
      nonsignificant. In contrast, treatment with PTH showed a highly significant
      increase in femoral neck biomechanical competence. Concurrent treatment with PTH
      plus estrogen or PTH plus Risedronate also significantly increased the femoral
      neck bone strength, but neither showed any advantage over treatment with PTH
      alone. It is concluded that treatment with PTH increases the strength of the
      femoral neck in estrogen-depleted rats in a highly significant manner, and that
      this effect is much more pronounced than the effect of the two antiresorptive
      agents estrogen or Risedronate. Thus, these findings provide further support for
      the anabolic effect of PTH and add weight to the argument for the promising
      potential of PTH in the treatment of postmenopausal osteoporosis.

PMID- 8299563
TI  - Glucocorticoids suppress interleukin-1 receptor antagonist synthesis following
      induction by endotoxin.
AB  - Glucocorticoids, as part of their physiological role in the control of
      inflammatory and immune processes, suppress the expression of IL-1 and other
      cytokines. We have found a dose-dependent inhibition by dexamethasone (10 nM to
      10 microM) of mRNA levels of the recently cloned IL-1 receptor antagonist (IL
      1ra) in endotoxin-stimulated human monocytes. At the same concentrations, both
      dexamethasone and cortisol inhibited the secretion of IL-1ra. These inhibitory
      effects were reversed by blocking glucocorticoid receptors with the specific
      antagonist RU 38486, but not by adding exogenous IL-1, even up to 100 ng/ml, to
      the monocytes. A similar inhibition of IL-1ra mRNA and protein secretion was
      found in monocytes obtained after dexamethasone administration in vivo. In
      addition, we observed parallel increases in glucocorticoid and IL-1ra levels
      following endotoxin administration to normal volunteers. Our results show that
      glucocorticoids shut down not only IL-1 but also IL-1ra expression, ruling out
      induction of IL-1ra as part of the glucocorticoid antiinflammatory mechanism. The
      control of the delicate immunoregulatory balance of the IL-1/IL-1ra system during
      endotoxemia underscores the physiological importance of glucocorticoids in the
      final control of immune responses.

PMID- 8299564
TI  - Prolonged absence of ovarian hormones in the ewe reduces the adrenocorticotropin
      response to hypotension, but not to hypoglycemia or corticotropin-releasing
      factors.
AB  - The ACTH responses to hypotension, hypoglycemia, CRF, arginine vasopressin (AVP),
      and the combination of CRF and AVP were compared to determine whether there was a
      general decrease in ACTH responses to these stimuli in ovariectomized ewes
      compared to intact animals. The ovariectomized ewes were studied either 2-4 weeks
      post-ovariectomy (acute) or 4-7 months post-ovariectomy (chronic). Each ewe was
      subjected to saline control infusion, nitroprusside-induced hypotension (100
      micrograms/min for 10 min), insulin-induced hypoglycemia (25 U porcine insulin),
      CRF (1 microgram/min for 60 min), AVP (0.2 microgram/min), and a combination of
      CRF plus AVP. In each experiment, plasma ACTH concentrations were measured at 10
      min intervals for 1 h. The peak ACTH concentrations were significantly lower in
      response to hypotension in the chronic ewes compared to those in either the
      intact or acute group. The ACTH response to hypoglycemia was not significantly
      reduced in either ovariectomized group. The ACTH responses to CRF, AVP, and the
      combination of both were not significantly reduced in either ovariectomized
      group. The results suggest that the effect of ovariectomy on the ACTH response to
      stress occurs at a site within the brain and does not involve altered pituitary
      responsiveness to CRF or AVP.

PMID- 8299565
TI  - Efficacy and specificity of L-692,429, a novel nonpeptidyl growth hormone
      secretagogue, in beagles.
AB  - L-692,429 is a substituted benzolactam that has recently been shown to stimulate
      GH secretion from rat pituitary cells in vitro with an ED50 of 60 nM. In the
      current studies, we evaluated the efficacy and specificity of L-692,429 as a GH
      secretagogue in beagles. L-692,429 at 0.1, 0.25, or 1.0 mg/kg or saline vehicle
      was administered iv to four male and four female beagles in a balanced cross-over
      design. Blood samples were collected up to 75 min posttreatment, and serum was
      assayed for GH, cortisol, PRL, and LH. Mean peak serum GH levels were
      significantly increased (P < 0.05) by L-692,429 to 13 +/- 2 (mean +/- SEM) ng/ml
      (0.1 mg/kg), 39 +/- 6 ng/ml (0.25 mg/kg), or 71 +/- 11 ng/ml (1.0 mg/kg) over the
      saline control value of 3.6 +/- 0.6 ng/ml. Mean peak GH levels occurred at 15 min
      and had returned to near-baseline levels by 75 min. There was no difference in
      response between sexes. Mean peak cortisol levels were significantly increased (P
      < 0.05) by 2.2-, 2.7-, and 3.1-fold above control levels (3.0 +/- 0.2
      micrograms/dl) at 25-35 min and returned to near-baseline levels by 75 min. PRL
      was slightly decreased after L-692,429 treatment, whereas LH was not affected. In
      a second study, three groups of three male beagles each were administered 5.0
      mg/kg L-692,429, iv; iv saline, or 2.2 U/kg ACTH, im. Blood was collected for 8 h
      posttreatment and assayed for GH, cortisol, ACTH, aldosterone, PRL, insulin, T3,
      and T4. L-692,429 administration significantly increased (P < 0.05) GH over the
      control level (6.0 +/- 3.6 ng/ml) to 133 +/- 14 ng/ml by 15 min, with a return to
      pretreatment levels by 120 min. Cortisol levels were significantly increased (P <
      0.05) by 2.0-fold (L-692,429) or 2.9-fold (ACTH) over the saline control peak
      concentration of 5.6 +/- 1.6 micrograms/dl and were associated with concurrent
      increases in ACTH levels of 1.2-fold (L-692,429) or 2.1-fold (ACTH) over the
      saline control peak concentration of 67 +/- 20 pmol/L. Aldosterone, PRL, T3, and
      T4 were not significantly affected after L-692,429 administration; however, ACTH
      treatment significantly increased aldosterone (P < 0.05). These data demonstrate
      that L-692,429 is a novel nonpeptidyl secretagogue that stimulates a marked, but
      transient, increase in serum GH levels in the dog.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8299566
TI  - Regulation of the progesterone receptor gene by gonadotropins and cyclic
      adenosine 3',5'-monophosphate in rat granulosa cells.
AB  - We have examined the effects of the pituitary gonadotropins on expression of the
      progesterone receptor (PR) gene in rat ovary and in granulosa cell cultures. Both
      gonadotropins (LH/hCG and FSH) rapidly induce PR mRNA expression in the granulosa
      cells of preovulatory follicles in vivo. Gonadotropins also effectively induce PR
      mRNA expression in primary cultures of rat granulosa cells, and this action can
      be mimicked by agents that elevate intracellular cAMP (forskolin or 8-bromo
      cAMP). Estrogen does not induce PR mRNA expression in these cells. The cAMP
      induced PR mRNA expression in rat granulosa cells is blocked by an inhibitor of
      transcription, but not by an inhibitor of protein synthesis. Structural
      characterization of the rat PR gene 5'-flanking region indicates that the
      proximal promoter does not contain a consensus cAMP response element. However,
      when luciferase fusion genes containing a 1375-basepair rat PR gene promoter were
      transiently transfected into rat granulosa cells, luciferase activity could be
      stimulated several-fold by hCG or forskolin, but not by estrogen. These results
      indicate that gonadotropins, most likely acting through a pathway mediated by
      cAMP, are able to stimulate transcription of the PR gene in rat granulosa cells
      and suggest a mechanism for regulating the intraovarian actions of progesterone.

PMID- 8299567
TI  - Effects of differentiation on neuropeptide-Y receptors and responses in rat
      pheochromocytoma cells.
AB  - Undifferentiated rat pheochromocytoma PC12 cells resemble immature adrenal
      chromaffin cells, express neuropeptide-Y (NPY) receptors of the Y1 subtype, and
      synthesize catecholamines as well as NPY. In the present study, we examined how
      phenotypic alteration of PC12 cells by nerve growth factor (NGF) or
      glucocorticoid affected cellular responsiveness to NPY and related agonists,
      especially with regard to modulation of catecholamine overflow. Unlike
      undifferentiated PC12 cells, cells differentiated to a sympathetic neuronal
      phenotype with NGF were responsive to the Y2 receptor-selective agonist, NPY 13
      36. NPY 13-36 1) inhibited binding of [125I]NPY 1-36, 2) inhibited accumulation
      of evoked cAMP, and 3) inhibited evoked catecholamine overflow. NGF
      differentiated cells were also responsive to the Y1 receptor-selective agonist
      [Leu31,Pro34]NPY (LP-NPY). Like NPY-(13-36), LP-NPY inhibited binding of
      [125I]NPY-(1-36); however, LP-NPY and NPY-(13-36) exerted their effects through
      heterogeneous receptors, as LP-NPY enhanced while NPY 13-36 inhibited evoked
      catecholamine overflow in NGF-differentiated cells, despite the fact that both
      agonists inhibited the evoked cAMP. In contrast to NGF-differentiated cells,
      cells differentiated to a mature chromaffin phenotype with dexamethasone were
      unresponsive to NPY-(13-36), nor did the Y2 agonist inhibit binding of [125I]NPY
      (1-36). Dexamethasone-differentiated PC12 cells were, however, responsive to LP
      NPY, as this agonist enhanced evoked catecholamine overflow and inhibited binding
      of [125I]NPY-(1-36). Peptide-YY also enhanced catecholamine overflow, but only
      significantly at 100 nM. The data suggest differential expression of NPY receptor
      subtypes on neuronal and endocrine cells where catecholamine overflow is a key
      feature. These studies further demonstrate inhibitory or excitatory modulation of
      catecholamine transmission by NPY via distinct receptor subtypes in homogeneous
      sympathoadrenomedullary models resembling sympathetic neurons and chromaffin
      cells.

PMID- 8299568
TI  - Characterization of the mitogen-activated protein kinase/90-kilodalton ribosomal
      protein S6 kinase signaling pathway in 3T3-L1 adipocytes and its role in insulin
      stimulated glucose transport.
AB  - Insulin exerts diverse effects on mitogenesis, metabolism, gene expression, and
      protein synthesis depending on the target cell type. A variety of extracellular
      serine/threonine kinases, including the ribosomal protein S6 kinases pp70
      ribosomal S6 kinase (pp70-S6K) and pp90-ribosomal S6 kinase (pp90rsk) and the erk
      encoded mitogen-activated protein (MAP) kinases pp44mapk/ERK-1 and pp42mapk/ERK
      2, have been postulated as mediators of insulin action. In this study, we have
      investigated the role of the MAP kinase/pp90rsk signaling pathway in insulin
      stimulated glucose transport in 3T3-L1 adipocytes. Differentiation of 3T3-L1
      fibroblasts into adipocyte-like cells was accompanied by a marked increase in the
      capacity of insulin to activate pp90rsk and pp44mapk. Whereas the maximal insulin
      stimulated pp90rsk and pp44mapk activities were only approximately 30% of the
      serum-stimulated activities in preadipocytes, the insulin-stimulated kinase
      activities in adipocytes were equal to or greater than the serum-stimulated
      activities. The increase in hormone receptor number accompanying differentiation
      accounted for the greater sensitivity, as overexpression of human insulin
      receptors in NIH-3T3 cells also conferred insulin-stimulatable kinase activity.
      In 3T3-L1 adipocytes, the stimulation of pp90rsk and pp44mapk activities was
      sufficiently rapid and hormone sensitive to convey a signal for increased hexose
      uptake. However, epidermal growth factor and fetal bovine serum were equipotent
      with insulin in stimulating pp90rsk and pp44mapk activities in adipocytes, but
      were without effect on hexose uptake. These data indicate that activation of
      these enzymes is not sufficient for the acute stimulation of glucose transport.

PMID- 8299569
TI  - NPXY motif in the insulin-like growth factor-I receptor is required for efficient
      ligand-mediated receptor internalization and biological signaling.
AB  - The NPXY motif that was identified in the low density lipoprotein receptor serves
      as an internalization signal, and subsequent studies have indicated that the NPXY
      sequence is also an important recognition element for internalization of both
      insulin and transferrin receptors. The insulin-like growth factor (IGF-I)
      receptor contains an NPXY sequence (residues 947-950) in the immediate
      submembranous domain, and we sought to determine whether these residues play a
      role in facilitating ligand-mediated internalization of the IGF-I receptor. To
      study this, we have constructed stable cell lines expressing NPXY deletion mutant
      receptors (CHONPXY) or wild-type receptors (CHOWT). Ligand internalization
      studies showed that CHONPXY cells internalized [125I]IGF-I with a 40% defect (P <
      0.005) compared to the CHOWT cells. Ligand-mediated receptor internalization and
      down-regulation were decreased by 90% in CHONPXY compared to CHOWT cells. The
      kinase activity of the mutant receptors was also defective as a result of removal
      of the NPXY motif. This is in contrast to the insulin receptor, in which deletion
      of the NPXY motif or deletions of even larger portions of amino acids in
      proximity to the NPXY motif do not affect the kinase activity of the receptor.
      Finally, the ability of the mutant receptors to mediate biological signaling is
      also defective, as measured by the thymidine incorporation assay.

PMID- 8299570
TI  - Topology of 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4-isomerase
      in adrenal cortex mitochondria and microsomes.
AB  - 3 beta-Hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD)
      is a NAD(+)-dependent membrane-bound enzyme that catalyzes the oxidation of delta
      5-3 beta-hydroxysteroids to delta 4-3-keto structures during adrenal, gonadal,
      and placental steroidogenesis. Enzyme activity is located in both microsomes and
      mitochondria. In these experiments we examined the membrane topologies of 3 beta
      HSD in rat and calf adrenal microsomes and mitochondria by comparing access to
      the active sites of coenzyme and the inhibitor mersalyl, a nonpenetrant organic
      mercurial anion. Microsomal activity required exogenous NAD+ and was inhibited by
      mersalyl, indicating that the active site faced the medium in vitro and the
      cytoplasm in vivo. In contrast, mitochondrial 3 beta HSD used matrix space NAD+,
      was inhibited by reduction of intramitochondrial NAD(P)+, and was insensitive to
      mersalyl. Mitochondrial activity was decreased by exogenous NADH (apparent Ki,
      2.8 microM) and increased by added NAD+ (apparent Ka, 2.4 microM). However,
      mersalyl blocked the effects of exogenous NADH and NAD+ and returned the activity
      to that observed before coenzyme addition. The membrane-sidedness of the NAD+
      activation was examined further in submitochondrial particles prepared by
      sonication of pyridine nucleotide-depleted calf adrenal cortex mitochondria.
      Particles were prepared in the absence or presence of 10 mM NAD+ and contained
      none or 2.9-7.3 nmol NAD+/mg protein, respectively. Both groups of
      submitochondrial particles required exogenous NAD+ for 3 beta HSD activity,
      indicating that the active site faced the medium (the particles were everted),
      and the contained NAD+ was inside the particles. However, 3 beta HSD activity was
      increased 12-140% in particles that contained NAD+. The results suggest that
      mitochondrial 3 beta HSD is an integral inner membrane protein, that the active
      site faces the matrix space and is influenced by coenzyme availability, and that
      a regulatory site(s) faces the intermembrane space. Binding of NAD+ or NADH to
      this external site increases or decreases, respectively, the rate of catalysis at
      the active site. Mitochondrial 3 beta HSD activity may be enhanced by oxidation
      of intermembrane space NADH via an active rotenone- and antimycin-a-insensitive
      NADH oxidase.

PMID- 8299571
TI  - The effect of fasting on insulin-like growth factor-I nuclear transcript
      abundance in rat liver.
AB  - The abundance of insulin-like growth factor I (IGF-I) messenger RNA (mRNA) is
      decreased in the liver of fasting, protein-restricted, and energy-restricted
      rats. The extent to which this decrease in steady state mRNA abundance may be
      attributed to a decrease in IGF-I gene transcription remains unresolved. In the
      present study, we used an RNase protection assay to quantify IGF-I nuclear
      transcript (pre-mRNA) and mRNA abundance in whole cellular RNA isolated from
      liver of fasted and nonfasted male rats (4-6 weeks of age). The results of the
      RNase protection assay of IGF-I nuclear transcripts were strongly correlated with
      the results of nuclear transcription elongation (run-on) assays (r > 0.90; P <
      0.001). In addition, the RNase protection assay allows for a greater capability
      for sensitively monitoring gene transcription in a large number of samples. In
      four different experiments, a consistent decrease in the quantity of IGF-I
      nuclear transcripts was observed in liver of animals fasted for 72 h, whereas IGF
      I pre-mRNA abundance in animals fed ad libitum was highly variable (average
      intraassay coefficient of variation = 74% vs. 34% for nonfasted and fasted
      groups). When data from the four experiments were pooled, fasting reduced IGF-I
      pre-mRNA and mRNA levels by 78% and 70% (P < 0.001), respectively. Fasting also
      caused a significant decrease in mRNA and nuclear transcript abundance for
      another nutritionally sensitive gene, the gene encoding transthyretin (TTR). To
      determine whether the decrease in IGF-I and TTR nuclear transcripts was gene
      specific, levels of nuclear transcripts for serum albumin, H-ferritin, and
      ribosomal RNA were also quantified. The results indicated that serum albumin, H
      ferritin, and ribosomal RNA nuclear transcripts were not decreased by fasting,
      demonstrating that the negative effect of fasting was specific for IGF-I and TTR.
      In summary, these results indicate that IGF-I and TTR nuclear transcripts are
      specifically decreased by fasting. The decrease in IGF-I mRNA is matched by a
      similar decrease in IGF-I nuclear transcripts, suggesting that fasting controls
      IGF-I gene expression primarily at the transcriptional level.

PMID- 8299572
TI  - Evidence for a direct hepatotrophic role for insulin in the fetal rat:
      implications for the impaired hepatic growth seen in fetal growth retardation.
AB  - Perturbations of fetal growth produce parallel but disproportionate changes in
      fetal liver growth that correlate with circulating fetal insulin concentration.
      We have studied the effects of insulin and two hepatotrophic factors,
      transforming growth factor-alpha (TGF alpha) and hepatocyte growth factor (HGF),
      on DNA synthesis by fetal and adult rat hepatocytes in primary culture. Using
      serum-free Minimum Essential Medium, fetal hepatocytes synthesized DNA without
      growth factors, unlike adult hepatocytes. Insulin augmented fetal hepatocyte DNA
      synthesis after 16-24 h in culture. In contrast, TGF alpha or HGF maximally
      stimulated fetal hepatocyte DNA synthesis after 40 h in culture. Insulin and TGF
      alpha were not synergistic in stimulating fetal hepatocyte DNA synthesis, but
      were synergistic in their action on adult hepatocytes. Brief (10-min) exposure of
      fetal hepatocytes to TGF alpha or HGF, but not insulin, activated mitogen
      activated protein kinases 4-fold. Prolonged (24-h) exposure to TGF alpha or HGF
      abolished the ability of either to activate mitogen-activated protein kinases,
      whereas insulin had no effect. Maternal fasting for 48 h before isolation and
      culturing of fetal hepatocytes abolished the in vitro stimulation of DNA
      synthesis by insulin without affecting TGF alpha action. We conclude that insulin
      has growth-promoting actions on fetal hepatocytes that are distinct and
      independent from those of TGF alpha of HGF.

PMID- 8299573
TI  - Continuous but not intermittent administration of growth hormone to
      hypophysectomized rats increases apolipoprotein-E secretion from cultured
      hepatocytes.
AB  - Hypophysectomy of female rats has been shown to decrease the serum levels of
      apolipoprotein E (apoE). Continuous but not intermittent administration of GH to
      hypophysectomized (HX) rats increases these levels to those of normal rats,
      indicating that the sexually dimorphic secretion of GH is important in the
      regulation of apoE metabolism. In this study, these effects of GH were further
      investigated by studying the biosynthesis and secretion of apoE from isolated
      hepatocytes. Hepatocytes were isolated from HX rats as well as from HX rats that
      had received hormonal treatment with T4 and cortisol (C) or T4 and C together
      with GH given either as two daily sc injections (GH x 2) or as a continuous
      infusion (GHc). Hypophysectomy decreased by 47% the amount of apoE present in the
      culture medium after a 4-h incubation. Treatment of HX rats with T4 and C alone
      or in combination with GH x 2 did not influence the amount apoE present in the
      medium, whereas treatment with T4, C, and GHc increased the amount of apoE to
      that of normal controls. The different levels of apoE in the medium was not due
      to differences in the disappearance of apoE, indicating that it was caused by
      changes in the rate of apoE secretion. Consistent with this, hypophysectomy
      decreased the rate of intracellular accumulation of apoE measured by incubation
      of the cells with [35S]methionine for 0, 8, and 20 min. Treatment with T4, C, and
      GHc increased the rate of accumulation, but T4, C, and GH x 2 had no effect. The
      differences in the initial rate of intracellular accumulation of apoE were not
      due to variations in apoE messenger RNA pools or to differences in the
      degradation of apoE at a step early in the secretory pathway. These results
      indicate that the differences in the initial rate of accumulation of apoE results
      from differences in the translational rate. The major amount of apoE that was
      secreted to the medium appeared in the high-density lipoprotein fraction, whereas
      small amounts were present in the very-low-density lipoprotein fraction (VLDL).
      Hypophysectomy decreased the amount of newly secreted apoE in the VLDL fraction.
      Only therapy with T4, C, and GHc could restore the normal distribution of apoE in
      the VLDL fraction. In conclusion, the results indicate that the secretory pattern
      of GH is involved in the regulation of the apoE secretion by influencing the rate
      of translation.

PMID- 8299574
TI  - Hybridization histochemical localization of activin receptor subtypes in rat
      brain, pituitary, ovary, and testis.
AB  - We have studied the distribution of activin receptor gene expression in the
      brain, pituitary, ovary, and testis of the adult rat by in situ hybridization,
      using probes complementary to the mRNAs encoding the mouse activin receptor
      subtypes II and IIB (ActRII and ActRIIB). Throughout the brain, ActRII mRNA
      expression was stronger than that of ActRIIB, and the patterns of expression were
      similar, although not identical. The most intense sites of activin receptor gene
      expression were the hippocampal formation, especially the dentate gyrus (ActRII),
      taenia tecta, and induseum griseum; the amygdala, particularly the amygdaloid
      hippocampal transition zone; and throughout the cortical mantle, including the
      primary olfactory cortex (piriform cortex and olfactory tubercle); other regions
      of the cortex showing lesser degrees of hybridization included the cingulate
      cortex, claustrum, entorhinal cortex, and subiculum. In addition, moderate levels
      of expression were observed in several hypothalamic areas involved in
      neuroendocrine regulation, such as the suprachiasmatic, supraoptic,
      paraventricular, and arcuate nuclei. Moreover, activin receptors were also
      expressed in regions with inputs to the hypothalamus, both in the forebrain (bed
      nucleus of the stria terminalis and medial preoptic area) and within the
      brainstem (nucleus of the solitary tract, dorsal motor nucleus of the vagus,
      locus coeruleus, and mesencephalic raphe system). ActRII mRNA was observed in the
      intermediate lobe of the pituitary and, less prominently, in the anterior lobe,
      whereas ActRIIB appeared to be weakly expressed throughout all three pituitary
      divisions. In both male and female gonads, activin receptor message was clearly
      present in germ cells, and ActRII was the predominant form. In the ovary, in
      addition to an intense signal in the oocyte, activin receptor was expressed in
      corpus luteum and granulosa cells during diestrous day 1. In the testis, there
      was a strong ActRII signal in rounded spermatids, and a moderate signal in
      pachytene spermatocytes. In contrast, ActRIIB was absent within tubules, but
      weakly expressed in interstitial and Leydig cells. This is the first report of
      the distribution of activin receptor message in adult mammalian tissues. Although
      consistent with some previously suggested functional associations of activin
      containing pathways in the brain, this pattern of expression suggests a greater
      role for activin than was previously appreciated in cortical, limbic, and
      somatosensory pathways and in the maturation of germ cells in the gonads of both
      male and female rats.

PMID- 8299575
TI  - Age dependence and modulation by gonadectomy of the sex-specific response of rat
      diaphyseal bone to gonadal steroids.
AB  - We have previously reported that diaphyseal bone of prepubertal rats responds in
      a sex-specific manner to gonadal steroids, 24 h after steroid injection, by
      increases in creatine kinase (CK) specific activity and the rate of DNA
      synthesis. We have also shown that hormonal intervention abolished the sex
      specific response of diaphyseal bone to sex steroids. In the present study, we
      examined the responsiveness of diaphyseal bone and cartilage to gonadal steroids
      in male and female Wistar-derived rats at ages between 5 days and 1 yr. In both
      diaphyseal bone and cartilage of untreated control rats, a peripubertal peak of
      CK specific activity was seen, which was more pronounced in females. Diaphyseal
      bone, unlike epiphyseal cartilage, responded specifically to a single injection
      of 17 beta-estradiol (E2; 5 micrograms/rat) in females and to 5 alpha
      dihydrotestosterone (DHT; 50 micrograms/rat) in males. The highest response
      occurred peripubertally, but was skewed toward prepubertal ages in males and
      postpubertal ages in females. To study the effect of gonadectomy on this sex
      specific response of diaphyseal bone, rats were gonadectomized at the age of 24
      or 180 days and from 4 days to 4 weeks thereafter were challenged with either E2
      or DHT. Diaphyseal bones of gonadectomized rats of either sex responded to both
      E2 and DHT, beginning 7 days after surgery. Thus, in gonadectomized rats, there
      was a loss of the sex specificity of response to steroid hormones, which could be
      restored by replenishment, by five daily injections, of the characteristic
      hormone of each sex. In the epiphyseal cartilage, the same replenishment schedule
      resulted in acquisition of a sex-specific response in both sexes, not seen
      previously. These data in conjunction with the previously reported hormonal
      modulation of sex-specific responses, are consistent with a developmental
      acquisition of diaphyseal sex steroid specificity that requires for its
      maintenance the presence of appropriate amounts of the characteristic gonadal
      steroid in each sex.

PMID- 8299576
TI  - Thyrotropin-releasing hormone (TRH) gene expression in the anterior pituitary. I.
      Presence of pro-TRH messenger ribonucleic acid and pro-TRH-derived peptide in a
      subpopulation of somatotrophs.
AB  - We have previously reported the presence of authentic pro-TRH-derived peptides in
      cultured anterior pituitary (AP) cells. The present studies were undertaken to
      determine whether pro-TRH mRNA could be demonstrated in the AP and to elucidate
      the cell type expressing pro-TRH. AP cells were cultured for up to 18 days,
      during which time the content of both TRH and prepro-TRH-(25-50) rose
      significantly (P < 0.01). In contrast, the cellular contents of LH, FSH, TSH, and
      ACTH fell significantly (P < 0.01), whereas that of GH increased by 45.9% (P <
      0.05). Northern blot analysis revealed that the levels of pro-TRH mRNA extracted
      from AP cells (18 days in culture) were similar to those in hypothalamic tissue
      from adult male rats, indicating a high relative abundance of this mRNA in the
      AP. In situ hybridization experiments showed a dense accumulation of silver
      grains over a subpopulation of cultured AP cells. A combination of in situ
      hybridization for pro-TRH mRNA and immunocytochemistry for pituitary hormones
      revealed colocalization of pro-TRH mRNA and GH in a subpopulation of
      somatotrophs. No colocalization with LH-, TSH-, PRL-, or beta-endorphin
      containing cells was observed. Immunocytochemistry at the electron microscopic
      level demonstrated that prepro-TRH-(25-50) was contained in a subpopulation of
      secretory granules in AP cells expressing this pro-TRH-derived sequence. These
      studies demonstrate that pro-TRH mRNA is present in cultured AP cells in high
      concentration and that the pro-TRH gene is expressed within a subpopulation of
      somatotrophs.

PMID- 8299577
TI  - Thyrotropin-releasing hormone gene expression in the anterior pituitary. II.
      Stimulation by glucocorticoids.
AB  - The present studies were undertaken to determine whether glucocorticoids (GC)
      regulate TRH gene expression in cultured anterior pituitary (AP) cells. AP cells
      derived from 15-day-old male rats were cultured for up to 18 days in Dulbecco's
      Modified Eagle's Medium-L-15 medium supplemented with 1) fetal calf serum (FCS),
      2) charcoal-treated FCS, 3) normal rat serum, or 4) serum from rats that were
      adrenalectomized, rendered hypothyroid, and gonadectomized (ATG rat serum).
      Dexamethasone (Dex) or corticosterone (Cort) was added to the culture medium at
      various concentrations with exposure times ranging from 4-18 days. TRH and prepro
      TRH-(25-50) in cellular extracts and release media were measured by RIA, and pro
      TRH mRNA was determined by Northern blot analysis and in situ hybridization. Dex
      substantially stimulated cellular TRH and prepro-TRH-(25-50) accumulation under
      all culture conditions investigated, i.e. in medium supplemented with any of the
      four sera. TRH gene expression did not occur in medium supplemented with charcoal
      treated FCS or ATG rat serum. Pretreatment with 10(-8) M Dex caused a significant
      increase in basal as well as cAMP- or phorbol ester-stimulated release of the
      peptide. Steady state pro-TRH mRNA levels rose 6.8- and 4.2-fold (both P < 0.01)
      after treatment with 10(-8) M Dex for 4 and 12 days, respectively. In situ
      hybridization experiments revealed that this rise in pro-TRH mRNA levels was
      probably the result of an increase in the number of AP cells expressing pro-TRH.
      Both Dex and Cort caused a dose-dependent increase in TRH accumulation, but Cort
      was approximately 40 times less potent than Dex. These results indicate that GC
      stimulate TRH gene expression in cultured AP cells. The presence of GC in culture
      medium is a prerequisite for the occurrence of TRH gene expression in the AP. As
      GC have been reported to reduce pro-TRH mRNA levels in the hypothalamus in vivo,
      our results may provide an example of the tissue-specific effects of GC on TRH
      gene expression.

PMID- 8299578
TI  - Thyrotropin-releasing hormone gene expression in the anterior pituitary. III.
      Stimulation by thyroid hormone: potentiation by glucocorticoids.
AB  - The present study was designed to investigate the effect of thyroid hormone on
      TRH gene expression in cultured anterior pituitary (AP) cells. AP cells derived
      from 15-day-old male rats were cultured for up to 14 days in Dulbecco's Modified
      Eagle's Medium-L-15 medium supplemented with either fetal calf serum (FCS) or FCS
      devoid of thyroid hormones. T4 or T3 were added at various concentrations to the
      medium for a duration of 2-14 days. TRH and GH were measured by RIA, and pro-TRH
      mRNA levels were determined by semiquantitative in situ hybridization. Addition
      of both T3 and T4, but not the biologically inactive diiodothyronine,
      significantly stimulated TRH accumulation in AP cells. T3 increased TRH content
      in a time- and dose-dependent fashion and was much more potent than T4.
      Dexamethasone (Dex) also raised the content of TRH significantly. The combination
      of 10(-9) M T3 and 10(-8) M Dex dramatically potentiated the effect of either
      treatment alone (T3, 8.9-fold rise; Dex, 37.2-fold rise) and increased TRH
      accumulation 251.2-fold (all P < 0.01). Levels of pro-TRH mRNA mirrored TRH
      content data. T3, Dex, or the combination of both raised pro-TRH mRNA levels 1.9
      , 2.7 (both P < 0.05)-, and 11.1 (P < 0.01)-fold, respectively. The visualization
      of pro-TRH mRNA by in situ hybridization revealed that the combination of T3 and
      Dex treatment caused a substantial increase in the number of cells expressing pro
      TRH. The results presented here demonstrate that T3 increases pro-TRH gene
      expression in cultured AP cells and that glucocorticoids markedly potentiate this
      effect. As pro-TRH is expressed in a subpopulation of somatotrophs, our data
      suggest that the TRH gene in this location may be coordinately regulated with the
      GH gene.

PMID- 8299579
TI  - Granulocyte-macrophage colony stimulating factor suppresses lipopolysaccharide
      induced osteoclast-like cell formation in mouse bone marrow cultures.
AB  - Lipopolysaccharide (LPS) is a potent bone resorbing factor. We investigated the
      effect of LPS on osteoclast formation in three types of cultures. LPS inhibited
      osteoclast formation induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], in a dose
      dependent manner, in cultures of whole bone marrow cells without dexamethasone.
      LPS increased the amount of granulocyte-macrophage colony stimulating factor (GM
      CSF) in the culture supernatant, and anti-GM-CSF antiserum almost abolished the
      inhibition of osteoclast formation by LPS, thereby indicating that GM-CSF
      generated by treatment with LPS may be responsible for the inhibition of
      osteoclast formation. In cultures with dexamethasone, the amount of GM-CSF was
      decreased to one-third of that with 1,25(OH)2D3 alone and was not changed by
      treatment with LPS. In this culture system, LPS enhanced osteoclast formation. In
      the coculture system of nonadherent bone marrow cells and a stromal cell line in
      the presence of 1,25(OH)2D3 and dexamethasone, where no detectable GM-CSF was
      present in the supernatant, LPS markedly enhanced osteoclast formation, whereas
      exogenously added GM-CSF (100 pg/ml) almost completely inhibited osteoclast
      formation. LPS stimulated pit formation on dentin slices by the osteoclast-like
      cells formed by in vitro culture system.

PMID- 8299580
TI  - Adrenalectomy-induced alterations of calmodulin-dependent hippocampal adenylate
      cyclase activity: role of guanine nucleotide-binding proteins.
AB  - Ca2+/calmodulin-dependent processes are altered by manipulations of the
      hypothalamic-pituitary-adrenal axis. In particular, adrenalectomy (ADX)
      attenuates hippocampal, but not cortical, calmodulin-dependent adenylate cyclase
      activity measured during the active (waking) phase of rats. The involvement of
      calmodulin- and guanine nucleotide (G)-binding proteins in the effects of ADX on
      the activity of calmodulin-dependent adenylate cyclase were investigated. In
      hippocampal membranes, inclusion of the GTP antagonist guanosine 5'-O-(2
      thiodiphosphate) (250 microM) caused pronounced inhibition of calmodulin
      stimulated adenylate cyclase activity. Guanosine 5(1)-O-(2-thiodiphosphate) had
      much smaller effects on calmodulin-independent (basal and forskolin-stimulated)
      enzyme activity. Substitution of Mn2+ for Mg2+ in the assay medium increased
      basal and forskolin-stimulated adenylate cyclase activity, but abolished
      calmodulin-dependent activation of this enzyme in both hippocampal and cortical
      membranes. These treatments blunted ADX-induced attenuation of hippocampal
      adenylate cyclase. ADX, with or without corticosterone administration (40 mg/kg,
      sc, once daily), failed to alter either Gi alpha or Gs alpha membrane protein
      content in either hippocampus or cortex. The levels of major membrane calmodulin
      binding proteins in hippocampus and cortex also were not significantly altered by
      ADX. These results confirm that hormonal and biochemical regulation of calmodulin
      dependent adenylate cyclase is distinct from that of other adenylate cyclase
      family members. Changes in Gs alpha and Gi alpha protein content alone cannot
      account for the effects of ADX on this enzyme. Overall, our studies suggest that
      the effects of ADX on calmodulin-dependent adenylate cyclase may occur through a
      reduction in the absolute amount of the catalytic subunit or an alteration(s) in
      the efficiency of coupling between adenylate cyclase and its modulators.

PMID- 8299581
TI  - Cellular-tissue localization and regulation of the GLUT-1 protein in both the
      embryo and the visceral yolk sac from normal and experimental diabetic rats
      during the early postimplantation period.
AB  - We investigated the tissue-specific developmental expression and localization of
      GLUT-1 protein in the rat embryo and visceral yolk sac (VYS) during the
      organogenic periods of normal rats. The expression of GLUT-1 protein was then
      compared to that of experimental diabetic rats to test whether the diabetic state
      would affect the regulation of the glucose transporter during the early
      postimplantation periods (9.5-14.5 days), as we have previously demonstrated that
      GLUT-1 protein in embryo and VYS was down-regulated in culture with hyperglycemic
      medium. In the embryo, GLUT-1 protein was highly expressed during the early
      stages of organogenesis (between 9.5-12.5 days) and declined thereafter, whereas
      in the VYS, its strong expression was observed at the later stages (from 12.5
      14.5 days). Immunohistochemical localization of the GLUT-1 protein in the embryo
      during the main periods of neurulation (9.5-11.5 days) showed that GLUT-1
      immunoreactivity was principally observed in the neuroepithelial cells of the
      neural tube and also noted in the primitive heart, primitive gut, otic, and optic
      vesicles. At 12.5 days, GLUT-1 protein started to be expressed in the
      microvessels at the cranial portions of the neural tube, although its expression
      in the neuroepithelial cells still remained at the caudal (tail) portions of the
      neural tube. In the later stages (13.5-14.5 days) after completion of neural tube
      formation, GLUT-1 protein immunoreactivity substantially decreased in the
      neuroepithelial cells and was found mainly in the microvessels of the brain
      vesicles and spinal cord, whereas it continued to be expressed in the heart and
      eyes. In the VYS, its immunoreactivity was noticeably confined to the endodermal
      layer, which started as a simple layer and developed wave-like folds in the later
      stages. The levels of GLUT-1 protein in embryo and VYS from diabetic rats,
      determined by Western blot analysis, were not down-regulated compared to those in
      control rats at the different gestational days. Likewise, comparison of GLUT-1
      protein immunoreactivity of various tissues in embryo and VYS, focusing on the
      neural tube, also revealed no significant differences between the two groups. We
      demonstrated that GLUT-1 protein is abundantly expressed in embryonic tissues and
      VYS during the early periods of organogenesis. The lack of down-regulation and
      the continuous abundant expression of the GLUT-1 protein despite the diabetic
      state in embryo and VYS during the early postimplantation periods may increase
      delivery of glucose from the VYS into various differentiating embryonic cells,
      leading to diabetes-induced congenital malformations.

PMID- 8299582
TI  - The extracellular amino-terminal region of the parathyroid hormone (PTH)/PTH
      related peptide receptor determines the binding affinity for carboxyl-terminal
      fragments of PTH-(1-34).
AB  - The recombinant human PTH/PTH-related peptide (PTHrP) receptor, when transiently
      expressed in COS-7 cells, binds [Nle8,18,Tyr34] bovine PTH-(7-34)amide [PTH-(7
      34)], human PTH-(10-34)amide [PTH-(10-34)], and bovine PTH-(15-34)amide [PTH-(15
      34)] with at least 50-fold higher affinity than does the rat receptor homolog. In
      contrast, PTH-(1-34) binding affinities are similar for both receptor homologs.
      To map those areas of the PTH/PTHrP receptors that determine the binding
      specificity for carboxyl-terminal fragments of PTH-(1-34), we constructed
      chimeric rat/human PTH/PTHrP receptors. These bound PTH-(1-34) with normal
      affinity and, therefore, must have an overall conformation that resembles that of
      native receptors. Chimeras with the amino-terminal extracellular domain of the
      human PTH/PTHrP receptor have a considerably higher binding affinity for PTH-(7
      34), PTH-(10-34), and PTH-(15-34) than do the reciprocal receptor constructs in
      which the amino-terminal region is from the rat PTH/PTHrP receptor. The opossum
      PTH/PTHrP receptor homolog also binds PTH-(7-34) with higher affinity than the
      rat receptor, and studies of rat/opossum chimeras confirm the importance of the
      amino-terminal extracellular domain in determining the PTH-(7-34) binding
      specificity. Mutant rat and human PTH/PTHrP receptors in which either residues 61
      105 of the extracellular region or most of the intracellular tail were deleted
      have PTH-(7-34) binding characteristics indistinguishable from those of either
      wild-type receptor. These findings indicate that the amino-terminal extracellular
      region of the PTH/PTHrP receptor contains a domain(s) that largely determines the
      binding affinity of amino-terminally truncated PTH analogs. This region,
      therefore, is likely to constitute a site for ligand-receptor interaction.

PMID- 8299583
TI  - The number of oligosaccharides borne by porcine thyroglobulin is variable.
AB  - Purified porcine thyroglobulin (Tg) was fractionated on a concanavalin A
      Sepharose 4B column by a step-wise elution with increasing concentrations of
      methyl alpha-mannoside (fraction A, 50 mM; B, 100 mM; C, 200 mM; D, 500 mM, and
      E, 1 M), and its fractional ratio was 12.8:28.6:26.4:19.7:12.4. These five
      fractions showed the same profile in polyacrylamide gel electrophoresis. The
      subfractions were analyzed for their relative contents in oligosaccharides of
      each structure type and for their monosaccharide contents. In fractions B, C, D,
      and E the former varied between 15-22% for triantennary complex-type, 47-60% for
      biantennary complex-type, and 22-30% for high mannose-type oligosaccharide.
      Fraction A showed a higher percentage of triantennary complex-type structures
      (36%) and a lower percentage of biantennary complex-type structures (17%). The
      monosaccharide numbers increased from fraction A to E: 85 to 135 mannose
      residues, 60 to 82 galactose residues, 84 to 115 N-acetyl glucosamine residues,
      and 22 to 28 sialic acid residues. After analysis of the number of mannose
      residues contained in the high mannose-type structures, it was possible to
      calculate the number of oligosaccharides borne by each Tg subfraction. This
      number was approximately the same for fractions A and B (22.4 and 21.7), then it
      increased from B to E (21.8 to 32.9). These results account for the separation
      obtained on the concanavalin A-Sepharose 4B column. Separation of the two first
      subfractions bearing the same number of oligosaccharides is certainly due to the
      higher number of high mannose-type structures in B. In conclusion, the studies
      reported here show that porcine Tg is heterogeneous, and mainly so in terms of
      total number of N-glycan structures.

PMID- 8299584
TI  - Squirrel monkey corticosteroid-binding globulin: primary structure and comparison
      with the human protein.
AB  - Squirrel monkey (Saimiri sciureus) corticosteroid-binding globulin (CBG) is the
      product of a 1.6-kilobase mRNA in the liver. Analyses of two overlapping cDNAs
      revealed that the squirrel monkey CBG precursor comprises 406 amino acids, the
      first 22 residues of which exhibit 91% identity with the human CBG leader
      sequence. The mature form of squirrel monkey CBG, therefore, very likely
      comprises 384 amino acids and has a polypeptide mol wt of 42,854. Compared to
      human CBG, the squirrel monkey protein contains an additional residue (threonine)
      at position 144, and the two proteins exhibit 86% sequence identity if this is
      taken into account. Squirrel monkey CBG contains five consensus sites for N
      glycosylation, four of which are located in analogous positions in human CBG, and
      has two cysteine residues in the same relative positions as the cysteines in
      human CBG. Unlike CBG in most other species, squirrel monkey CBG appears to
      circulate as a dimer, and its affinity for glucocorticoids is remarkably low. We,
      therefore, expressed cDNAs for human and squirrel monkey CBGs in Chinese hamster
      ovary (CHO) cells and compared the physico-chemical properties of the products
      with those of the corresponding serum proteins. Squirrel monkey CBG is produced
      by CHO cells as a dimer, and its subunit size heterogeneity is similar to that
      associated with CBG in serum. In addition, the cortisol-binding affinity of
      squirrel monkey CBG produced by CHO cells is similar to that of the natural
      protein and is 5- to 8-fold lower than that of natural or recombinant human CBG.
      Mutants in which a threonine at position 144 was either added to human CBG or
      subtracted from squirrel monkey CBG were also expressed in CHO cells. This
      demonstrated that this additional amino acid in the squirrel monkey CBG sequence
      may actively contribute to its propensity for spontaneous dimerization, but does
      not account for its relatively low steroid-binding affinity.

PMID- 8299585
TI  - Regulation of myosin isozyme expression by vitamin D3 deficiency and 1,25
      dihydroxyvitamin D3 in the rat heart.
AB  - In this report, we demonstrate a significant inverse correlation between
      contractility and serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] levels and no
      correlation between contractility and serum levels of calcium, phosphate, or PTH.
      We also examined myosin isozyme distribution in vitamin D3-deficient rats,
      because myosin isozyme distribution can alter contractility. There was a
      significant increase in the levels of the V1 myosin isozyme in animals raised on
      a vitamin D3-deficient diet that maintained normal serum calcium and phosphate
      levels. There was no difference in the relative myosin isozyme distribution in
      animals raised on a hypocalcemia-yielding vitamin D3-deficient diet vs. animals
      raised on a control diet. As increased contractility has been observed in both
      groups of vitamin D3-deficient animals, a shift in myosin isozyme distribution
      cannot solely explain the increase in contractility previously observed in the
      vitamin D3-deficient rat heart. To determine whether 1,25-(OH)2D3 directly
      regulates myosin isozyme levels, we analyzed myosin isozyme distribution in
      primary cultures of ventricular myocytes. We found that 1,25-(OH)2D3 reduces
      total myosin levels, but does not alter myosin isozyme distribution. Thus, we
      show that the influence of vitamin D3 status on myosin isozyme expression in the
      intact rat involves a complex regulatory system of direct and indirect effects.

PMID- 8299586
TI  - Expression of messenger ribonucleic acids encoding the inhibin/activin system
      during mid- and late-gestation rat embryogenesis.
AB  - We recently demonstrated that inhibin/activin alpha-, beta A-, and beta B-subunit
      messenger RNAs (mRNAs) are localized in a variety of embryonic rat tissues from
      12-20 days post coitum (pc) and reported localizations consistent with possible
      growth effects of activin during rat embryogenesis. In the present study, we
      examined the tissue-specific distribution of mRNAs encoding all known players of
      the inhibin/activin system. In situ hybridization with radiolabeled RNA probes
      specific for mouse activin receptors (ActRII and ActRIIB), rat follistatin, and
      rat inhibin/activin subunits was used to examine the spatiotemporal expression of
      these molecules in adjacent sections of postimplantation rat embryos (8-20 days
      pc) as well as in midgestation placenta and uterine tissues (8-12 days pc). With
      the exception of the dorsal root ganglion and salivary gland, alpha- and beta B
      subunit mRNAs were found exclusively in reproductive tissues (brain, pituitary,
      and/or gonads). beta A-Subunit mRNA signal was observed in the brain and gonads
      as well as in a variety of other tissues during embryogenesis. ActRII mRNA was
      found exclusively in neuronal tissue from 14 days pc until birth. ActRIIB mRNA
      was also found in brain, spinal cord, and ganglion, but usually appeared earlier
      in development than the ActRII message. ActRIIB message was also expressed in a
      number of other tissues, in some cases along with beta A-subunit mRNA. In these
      tissues, ActRIIB expression was confined to epithelial and endothelial cell
      types. Follistatin message was observed in all tissues (except the heart and
      vessels) localizing beta A-subunit and/or ActRIIB but not in the same cell type.
      Outside the embryo, beta A-subunit mRNA was localized in the decidua capsularis
      during midgestation, whereas ActRIIB message was found in placenta as early as 9
      days pc. Expression of follistatin message was apparent in decidua from 8-11 days
      pc, then disappeared from this tissue and was abundant in myometrium at 12 days
      pc. These data suggest that: 1) inhibin and activin regulate aspects of the fetal
      reproductive system, whereas activin A may regulate the growth and
      differentiation of many embryonic tissues; 2) ActRII and ActRIIB serve different
      roles during development of the rat embryo; and 3) follistatin is in a position
      to modulate the effects of activin during postimplantation rat embryogenesis.

PMID- 8299587
TI  - High and polarized expression of GLUT1 glucose transporters in epithelial cells
      from mammary gland: acute down-regulation of GLUT1 carriers by weaning.
AB  - During lactation, the mammary gland shows high metabolic activity, which is
      dependent at least in part on the availability of glucose. We have studied the
      regulation of glucose transporter expression in different types of cell in rat
      mammary gland during the reproductive cycle. Glucose transporter expression
      varied markedly in the mammary gland during ontogeny. Thus, GLUT1 protein
      expression increased progressively during pregnancy, reaching the highest levels
      during lactation. A peak of lactation, GLUT1 protein content, expressed per g
      issue, was greater in mammary gland than in GLUT1-enriched tissues such as rat
      brain. In contrast, GLUT4 showed a marked decrease during pregnancy and
      practically disappeared during lactation. Regardless of the developmental stage,
      GLUT4 was expressed in adipocytes but not in epithelial cells from mammary gland.
      On the other hand, GLUT1 was expressed in both cell types. The overall pattern of
      GLUT1 and GLUT4 expression during the reproductive cycle reflects differences in
      the cell composition of the mammary gland. Thus, whereas adipocytes predominate
      before pregnancy, epithelial cells are the main cell type in the mammary gland
      during late pregnancy and lactation. Immunofluorescence and immunoelectron
      microscopy indicated that GLUT1 was essentially localized to the basolateral
      domain of epithelial cells in the mammary gland at peak of lactation, and hardly
      any labeling was found in the luminal membrane of epithelial cells. GLUT1
      expression was acutely regulated in epithelial cells from mammary gland. Thus,
      GLUT1 protein markedly decreased in lactating rats 24 h after abrupt weaning in
      the presence of a moderate decrease in GLUT1 mRNA levels. The effect of weaning
      on GLUT1 protein content was not due to the fall in the plasma concentration of
      PRL. Thus, bromocriptine treatment for 24 h decreased GLUT1 mRNA levels in the
      mammary gland, but did not alter the content of GLUT1 protein. Our results
      demonstrate 1) the existence of a high and polarized expression of GLUT1 glucose
      transporters in epithelial cells from mammary gland, and 2) that GLUT1 expression
      is acutely regulated at a posttranslational level by weaning; this is not
      mimicked by bromocriptine treatment, which rules out PRL as the regulatory factor
      involved in the effect.

PMID- 8299588
TI  - Role of growth factors and estrogen as modulators of growth, differentiation, and
      expression of gonadotropin subunit genes in primary cultured sheep pituitary
      cells.
AB  - Although the pituitary is known to produce several growth factors, their effects
      on pituitary cell growth and differentiation are still unclear, particularly in
      normal tissue. Using primary cultures of aged ewe pituitaries cultured in serum
      free conditions, we studied the effects of basic fibroblast growth factor (bFGF),
      epidermal growth factor (EGF), transforming growth factor-beta (TGF beta 1),
      insulin, and 17 beta-estradiol (E2) on the growth, differentiation, and
      expression of gonadotropin subunit genes. After 72-h incubation of the monolayer
      (day 5) with optimal concentrations of each factor, [3H]thymidine incorporation
      was increased significantly (P < 0.01) over the control values by 33 +/- 8% (mean
      +/- SEM; n = 3; 10 nM E2), 36 +/- 10% (1 ng/ml TGF beta 1), 83 +/- 12% (10 ng/ml
      bFGF), and 118 +/- 12% (1 nM EGF). Insulin showed a two-phase dose-response
      curve, increasing [3H]thymidine uptake by 34 +/- 9% at 10 ng/ml and by 63 +/- 13%
      at 10 micrograms/ml. Cell counting using a Coulter counter confirmed these
      results. Characterization of cell types by immunocytochemistry (avidin-biotin
      peroxidase complex technique) revealed that the cell cultures were predominantly
      gonadotrophs. However, the cultures contained cells that did not stain with any
      specific ovine or human antiserum against LH beta, FSH, TSH beta, PRL, GH, ACTH,
      or glial fibrillary acidic protein, but were of epithelial cell lineage, as shown
      by positive keratin staining. Treatment with EGF and bFGF increased the
      proportion of these undifferentiated pituitary cells and induced changes in their
      morphology to large cuboidal cells containing large nuclei. After treatment with
      E2, insulin, and TGF beta 1, pituitary cells remained differentiated, although
      with E2, staining for gonadotrophs was much reduced. Northern blot analysis
      revealed that E2 treatment for 0-48 h progressively reduced the mRNA for FSH beta
      (16 +/- 4.5% of control values) and LH beta (12.4 +/- 2.5%), but had little
      effect on the common alpha-subunit (88.4 +/- 4.6%). TGF beta 1, however,
      stimulated the expression of FSH beta subunit gene by 142 +/- 4.6% (P < 0.01) of
      the control value, but had no significant effect on LH beta and common alpha
      subunit genes. Insulin, EGF, and bFGF showed no significant effect on the
      expression of these three subunit genes. The data define the direct effects of
      growth factors and E2 on the growth and differentiation of normal sheep pituitary
      cells and gonadotrophs in particular, which may be of relevance to the
      pathophysiology of the pituitary and in the multistage process of pituitary
      tumorigenesis.

PMID- 8299589
TI  - Search for progestin receptors (PR) in prolactin-releasing peptidergic neurons:
      oxytocin neurons lack PR, but respond to gonadal steroids in monkeys.
AB  - Progesterone (P) increases PRL secretion in estrogen (E)-primed primates, but not
      by a direct action on lactotropes. Oxytocin is one of several hypothalamic
      hormones that stimulate PRL secretion. This study was conducted to determine
      whether oxytocin neurons directly mediate the action of P on PRL secretion.
      Hypothalamic sections from steroid-manipulated macaques were double immunolabeled
      for oxytocin and progestin receptors (PR). In addition, serum levels of oxytocin
      were measured in steroid-treated macaques, and hypothalamic levels of oxytocin
      were measured in monkeys under various physiological conditions. E treatment (28
      days) of spayed monkeys caused a significant increase in the number of PR
      positive neurons in the preoptic area, ventromedial nucleus, arcuate nucleus, and
      median eminence. Addition of P to the E treatment for the last 14 of 28 days did
      not change the number of PR-positive neurons in these areas. The number of PR
      positive neurons was low and was unchanged by steroid treatment in the supraoptic
      and rostral paraventricular nuclei. Oxytocin neurons rarely contained PR
      regardless of anatomical location, steroid treatment, or fixation protocol. Serum
      oxytocin levels increased with E treatment and increased further with
      supplemental P treatment. The rostral and medial basal hypothalamic content of
      oxytocin was significantly higher in macaques with mature gonads. In conclusion,
      oxytocin neurons do not express nuclear PR and probably do not transcriptionally
      respond to P. However, gonadal steroids apparently affect the production and
      release of oxytocin in vivo. Thus, it is possible that oxytocin neurons transduce
      the action of P on PRL secretion via stimulatory neurotransmission from another
      PR-containing neural system.

PMID- 8299590
TI  - Characterization of the synthesis and secretion of transforming growth factor
      alpha from salivary glands and saliva.
AB  - Whole saliva collected from rat, mouse, and human sources was found to contain
      high concentrations of transforming growth factor-alpha (TGF alpha) when analyzed
      by RIA. The concentrations of TGF alpha in unstimulated human saliva (age, 30-45
      yr; n = 10; 1.5 +/- 3.1 nM) was reduced with age (age, 55-70 yr; n = 10; 0.4 +/-
      0.1 nM), but increased in oral pathologies manifested in xerostomia (age, 57-70;
      n = 6; 0.8 +/- 0.2 nM) and Paget's disease (age, 58-76; n = 8; 2.0 +/- 0.6 nM).
      Immunohistochemical localization of TGF alpha in the salivary glands of rats and
      mice revealed specific immunostaining of the granular ductal cells of the parotid
      and submandibular glands. Reverse transcription followed by polymerase chain
      reaction amplification of total RNA from the parotid and submandibular glands of
      rats and mice demonstrated the presence of TGF alpha mRNA, suggesting endogenous
      synthesis by the salivary glands. Thus, salivary glands appear to be an exocrine
      source for a second member of the epidermal growth factor-like growth factor
      family in the oral cavity.

PMID- 8299591
TI  - Dehydroepiandrosterone sulfotransferase in the developing human fetus:
      quantitative biochemical and immunological characterization of the hepatic,
      renal, and adrenal enzymes.
AB  - The sulfation of the adrenal steroid dehydroepiandrosterone (DHEA) is a critical
      step in the provision of substrates for estrogen biosynthesis by the placenta
      during pregnancy. This enzyme reaction is catalyzed by a cytosolic
      sulfotransferase (ST) found in many key body tissues, and we have examined the
      ontogeny and localization of expression of this important enzyme in three
      tissues: the liver, adrenal, and kidney. Hepatic DHEA ST expression increased
      with advancing gestational age before reaching near-adult levels in the early
      postnatal period, suggesting an increased requirement for this enzyme in the
      liver as development progresses, whereas in the adrenal and kidney there was no
      obvious ontogenic pattern. The enzyme was expressed at a 5-fold higher level in
      the adrenal than in the liver and some 40-fold higher than in the kidney.
      Comparison of enzyme activity measurements and quantitation of the expression of
      DHEA ST by immunodot blot analysis with an anti-DHEA ST antibody preparation
      demonstrated the fragility of the enzyme activity and suggested that
      immunoquantitation was a superior method for assessment of levels of expression
      of this enzyme in widely different tissue sources. Examination of the
      localization of DHEA ST in these tissues by immunohistochemistry showed that in
      liver, DHEA ST was expressed in embryonic hepatocytes and continued to be
      expressed in these cells into adulthood, when there was some concentration of
      immunostaining around central veins. In the fetus, the adrenal enzyme was
      expressed in the fetal zone, whereas in adult tissue, staining was localized
      principally to the zona reticularis. Renal DHEA ST was present in the proximal
      and distal tubules, loops of Henle, collecting ducts, and their progenitors, but
      was at no time expressed in the vascular glomerulus. In light of the broad
      substrate specificity of this enzyme toward other steroids, in particular bile
      acids and cholesterol, the information presented forms a strong basis for further
      studies into the role of DHEA ST in modulating the activity of a number of
      biologically active and potentially toxic steroids in the developing human.

PMID- 8299592
TI  - Cells that express luteinizing hormone (LH) and follicle-stimulating hormone
      (FSH) beta-subunit messenger ribonucleic acids during the estrous cycle: the
      major contributors contain LH beta, FSH beta, and/or growth hormone.
AB  - There is a 2-fold increase in the percentage of gonadotropes bearing LH beta or
      FSH beta mRNAs or antigens as the cells approach proestrus. The purpose of this
      study was to identify the source of these cells with dual labeling techniques.
      The first hypothesis was that they stemmed from small monohormonal gonadotropes
      (containing only LH or FSH) that were driven to transcribe and translate the
      other gonadotropin. Alternatively, they may stem from other pituitary cell types.
      We detected the LH beta or FSH beta mRNAs by in situ hybridization (biotinylated
      oligonucleotide probes were detected by peroxidase-labeled avidin). Second,
      immunolabeling protocols localized the pituitary hormones. The percentages of
      cells with LH beta antigens and FSH beta mRNA increased to 81% of the LH beta
      antigen-bearing cells by the time of peak expression of FSH beta mRNA. Similarly,
      FSH beta antigen-bearing cells increased their expression of LH beta mRNA to 40%
      of such cells by the morning of proestrus. During the peak period of expression
      (the evening of proestrus), LH antigen-bearing cells had increased their
      expression of LH beta mRNA to 93%. Furthermore, 81% of the same cells expressed
      FSH beta mRNA. Thus, at least 80% of cells with LH antigens became bihormonal as
      the cells approached proestrus. This partially supports the first hypothesis for
      the origin of the new gonadotropes. However, the dual labeling studies also
      showed that 47% or 60% of cells with GH antigens expressed LH beta or FSH beta
      mRNAs, respectively, during peak expression (14% of pituitary cells contained
      gonadotropin mRNAs and GH antigens). Expression by cells with other antigens was
      low or absent (< 5% of pituitary cells). Perhaps a subset of somatotropes
      expresses gonadotropin mRNAs. Alternatively, the labeling could signify the
      presence of GH bound to GH receptors in gonadotropes. In either case, it appears
      that GH cells may be somehow linked to gonadotrope function as the cells approach
      proestrus.

PMID- 8299593
TI  - Agonists, but not antagonists, alter the conformation of the hormone-binding
      domain of androgen receptor.
AB  - Androgen receptors synthesized by translation in vitro form dimeric aporeceptor
      complexes with an androgen response element (ARE). Physiological and synthetic
      androgens elicit a conformational change in the receptor, which increases the
      mobility of receptor-ARE complexes in gel retardation assays. Neither a steroidal
      (cyproterone acetate) nor a non-steroidal (casodex) antiandrogen brings about the
      same effect and, at high concentrations, reverse the action of androgen agonists.
      When receptor-agonist complexes are subjected to a limited trypsin or
      chymotrypsin digestion, a protease-resistant 30-kDa fragment corresponding to the
      entire ligand-binding domain is formed. A similar fragment is not protected in
      the presence of antiandrogens. The C-terminal origin of the protected region was
      verified using mutated receptor forms: a mutant with a large N-terminal deletion
      behaves like the wild-type protein, but the properties of a hormone binding
      negative receptor, due to a single-base substitution at codon 807, are not
      influenced by androgen agonists or antagonists.

PMID- 8299594
TI  - Physiological and subjective responses to maximal repetitive lifting employing
      stoop and squat technique.
AB  - To establish safe levels for physical strain in occupational repetitive lifting,
      it is of interest to know the specific maximal working capacity. Power output, O2
      consumption, heart rate and ventilation were measured in ten experienced forestry
      workers during maximal squat and stoop repetitive lifting. The two modes of
      repetitive lifting were also compared with maximal treadmill running. In
      addition, electromyogram (EMG) activity in four muscles was recorded and
      perceived central, local low-back and thigh exertion were assessed during the
      lifting modes. No significant difference was found in power output between the
      two lifting techniques. Despite this the mean O2 consumption was significantly
      greater during maximal squat lifting [38.7 (SD 5.8) ml.kg-1.min-1] than maximal
      stoop lifting [32.9 (SD 5.7) ml.kg-1.min-1] (P < 0.001). No significant
      correlation was found between O2 consumption (in millilitres per kilogram per
      minute) during maximal treadmill running and maximal stoop lifting, while O2
      consumption during maximal squat lifting correlated highly with that of maximal
      treadmill running (r = 0.928, P < 0.001) and maximal stoop lifting (r = 0.808, P
      < 0.01). While maximal heart rates were significantly different among the three
      types of exercise, no such differences were found in the central rated perceived
      exertions. Perceived low-back exertion was rated significantly lower during squat
      lifting than during stoop lifting. The EMG recordings showed a higher activity
      for the vastus lateralis muscle and lower activity for the biceps femoris muscle
      during squat lifting than during stoop lifting. Related to the maximal voluntary
      contraction, the erector spinae muscle showed the highest activity irrespective
      of lifting technique.

PMID- 8299595
TI  - The effect of different exercise intensities on the fibrinolytic system.
AB  - The effects of moderate 30-min cycle ergometer exercise (aerobic metabolism)
      followed by short-term exercise at maximal capacity (anaerobic metabolism) on
      fibrinolytic activity were investigated in ten female and ten male healthy,
      untrained subjects. The following parameters of fibrinolytic activity were
      measured initially (t0), at the end of the aerobic phase (t1), at the end of the
      anaerobic phase (t2) and after a 30-min recovery period (t3): tissue plasminogen
      activator (PAt) activity, PAt concentration, plasminogen activator (PAt)
      activity, PAt concentration, plasminogen activator inhibitor (PAi) activity, and
      D-Dimer concentration. Moderate long-term exercise caused a slight but
      significant increase in PAt concentration and PAt activity (t1; P < 0.01),
      whereas short-term exercise at maximal capacity (t2) produced a substantial
      elevation in both these parameters (P < 0.01). This would suggest that PAt was
      not inhibited totally by PAi which would itself seem to be consumed during
      exercise. In addition, a slight exercise intensity-dependent increase in D-Dimer
      concentration was measured--circumstancial evidence not only for elevated
      fibrinolytic potential, but also for an actual increase in fibrin degradation
      (t2: P < 0.01). After t3 both PAt activity and D-Dimer concentration were still
      slightly but significantly increased. The results obtained in the tests of
      fibrinolytic activity showed no significant difference between the men and the
      women. It would seem that the release of PAt is more markedly stimulated by short
      term intense physical exercise than by long-term moderate exercise and actually
      causes increased fibrin degradation.

PMID- 8299596
TI  - An examination of the electromyographic fatigue threshold test.
AB  - The purpose of this investigation was to examine times to exhaustion at various
      percentages of the electromyographic fatigue threshold (EMGFT). Eight adult males
      [mean (SD), 21 (1) years] volunteered for the investigation. EMGFT was derived by
      determining the rate of rise in the electrical activity of the vastus lateralis
      [using integrated electromyography (iEMG)] over time (iEMG slope) for four
      fatiguing power outputs during cycle ergometry. The four power outputs were then
      plotted as a function of the four iEMG slope coefficients. The y-intercept of the
      power output versus iEMG slope coefficient graph was defined as the EMGFT. The
      intraclass correlation for repeated EMGFT tests was R = 0.65 (SEE = 7 W) and
      there was no significant (P > 0.05) difference between the mean (SD) values for
      test [260 (11) W] versus retest [262 (32) W]. Actual times to exhaustion were
      determined for work bouts at power outputs equal to 85, 100, 115, 130, and 145%
      of EMGFT. The mean (SD) times to exhaustion for these work bouts were 495 (231),
      225 (72), 135 (35), 94 (17), and 72 (14) s, respectively. A power curve was
      derived using the mean power outputs and mean times to exhaustion from the five
      rides at various percentages of EMGFT. The power curve provided estimates of the
      power outputs which could be maintained for 30 and 60 min. There were significant
      (P < 0.05) differences between the mean EMGFT (260 W) and the power outputs which
      could be maintained for 30 (151 W) and 60 (125 W) min.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8299597
TI  - The influence of dietary carbohydrate on performance of supramaximal intermittent
      exercise.
AB  - The present investigation examined the influence of dietary carbohydrate (CHO) on
      the performance of supramaximal intermittent exercise. A group of 14 moderately
      trained male students [mean age 21.0 (SD 1.6) years] completed a maximal oxygen
      consumption test and two identical 'maximal interval tests' (MIT1 and MIT2) over
      a 10-day experimental period. Each MIT involved five 60-s all-out periods of
      cycling (against 0.736 N.kg-1 body mass), with each period separated by 5 min of
      passive recovery. All subjects consumed a moderate CHO diet for 3 days preceding
      MIT1 (55.3% of energy intake as CHO) and were then randomly assigned to either a
      high CHO (83%), moderate CHO (58%) or low CHO (12%) diet for the 3 days
      separating MIT1 and MIT2. All food and drink consumed during the experimental
      period was weighed and recorded for later dietary analysis. Measurements of work
      done, exercise oxygen consumption (VO2), venous blood pH, plasma lactate and
      plasma glucose concentrations were compared between interval tests. Independent
      Student's t-tests revealed that the 5.6% increase in total work done recorded by
      the high CHO group and the 2.3% increase by the moderate CHO group between MIT1
      and MIT2, were significantly different to the 5.4% decrease in performance
      recorded for the low CHO group (P < 0.001 and P < 0.01, respectively). No
      significant differences in performance changes was found between the high and
      moderate CHO groups; 10 subjects in each of these groups would have been
      necessary to attain significance at the 0.05 level using the same
      procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299598
TI  - Maximal oxygen uptake, maximal voluntary isometric contraction and physical
      activity in young Danish adults.
AB  - In a randomly selected sample of 88 men and 115 women, aged 23-27 years from
      Denmark, maximal oxygen uptake (VO2max), maximal voluntary isometric contraction
      (MVC) in four muscle groups and physical activity were studied. The VO2max was
      48.0 ml.min-1.kg-1 and 39.6 ml.min-1.kg-1 for the men and the women,
      respectively. The MVC was 10% lower than in a comparable group of Danes of the
      same age and height studied 35 years ago. Only in men was sports activity
      directly related to VO2max (ml.min-1.kg-1; r = 0.31, P < 0.01). The MVC of the
      knee extensors was related to VO2max in the men (r = 0.31, P < 0.01), but there
      was no relationship between the other measurements of MVC and VO2max. In the
      women VO2max (ml.min-1.kg-1) was only related to body size, i.e. body mass index,
      percentage body fat and body mass [(r = -0.47, -0.48 (both P < 0.001) and -0.34
      (P < 0.01), respectively)]. There were differences in VO2max in the men,
      according to education and occupation. Blue collar workers and subjects attending
      vocational or trade schools in 1983 had lower VO2max, and more of them were
      physically inactive. In the women differences were also found, but there was no
      clear pattern among the groups. More of the women participated regularly in
      sports activity, but more of the men were very active compared to the women.

PMID- 8299600
TI  - Spine and total body bone mineral density and serum testosterone levels in male
      athletes.
AB  - The aim of this study was to compare the effects of intense endurance vs
      strengthening exercise on bone mass and serum testosterone levels in male
      athletes. Bone mineral density (BMD) of the total body and spine and serum
      testosterone levels were measured in male rowers (n = 12), triathletes (n = 8)
      and sedentary controls (n = 13). The total body scan also gave values for
      percentage body fat and regional bone densities. Calcium intake and physical
      activity levels were measured by questionnaire. The rowers had significantly
      higher BMD in the spine and total body than the triathletes (P < 0.01 and P <
      0.05 respectively) and sedentary controls (P < 0.01 and P < 0.05). There were no
      differences between the triathletes and controls. Serum testosterone levels were
      significantly lower in the triathletes than in the controls (P < 0.05); there was
      no significant difference between the rowers and controls. All groups fell within
      the normal range for testosterone. In a step-wise multiple regression, including
      age, body mass, height, calcium intake and activity, no single factor had a
      significant effect on spine BMD. Body mass had a significant effect on total body
      BMD and could account for the differences between the groups. A significant
      positive correlation was found between calcium intake and total body BMD. The
      heavy weight training typical of rowing training seemed to result in significant
      bone accretion. The low testosterone levels in the triathletes may have negated
      any positive effect of the increased exercise on BMD.

PMID- 8299599
TI  - Effects of aerobic long distance running training (up to 40 km.day-1) of 1-year
      duration on blood and endocrine parameters of female beagle dogs.
AB  - The effects of long distance running training on blood parameters, hormone
      responses and bone growth were studied in young growing dogs. A genetically
      uniform group of female beagles matched with respect to age and body mass were
      used. The runner dogs (n = 10) underwent gradually increased running exercise up
      to 40 km.day-1 on a treadmill with 15 degrees uphill gradient 5 days each week
      during a period of 1 year, while the littermate control dogs (n = 10) were kept
      in their cages throughout the study. Low plasma lactate concentrations of the
      runners measured immediately after the running training indicated the aerobic
      metabolism of the dogs while running. Significant decreases of blood haemoglobin
      concentrations (11%), blood erythrocyte number (10%), and erythrocyte packed cell
      volume (12%) were found in the runner group. Throughout the experiment, the value
      of thyroxine was slightly lower (13%) in the runners but no changes were found in
      tri-iodothyronine, free thyroxine, or cortisol serum concentrations. Serum
      oestradiol concentration at 56 weeks was significantly lower (42%) in the runner
      group than in the control group but was not as low (27%) at 70 weeks. Somatomedin
      C concentration had decreased significantly by 37% at the age of 56 weeks in the
      runner group but was again at the level of the control dogs at the end of
      experiment (at 70 weeks). Ulna and radius bone mass as a ratio to the body mass
      had significantly increased in the runners. It would seem from our study that
      long distance running has a positive effect on bone growth.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8299601
TI  - Motor unit recruitment during prolonged isometric contractions.
AB  - Motor unit recruitment patterns were studied during prolonged isometric
      contraction using fine wire electrodes. Single motor unit potentials were
      recorded from the brachial biceps muscle of eight male subjects, during isometric
      endurance experiments conducted at relative workloads corresponding to 10% and
      40% of maximal voluntary contraction (MVC), respectively. The recordings from the
      10% MVC experiment demonstrated a characteristic time-dependent recruitment. As
      the contraction progressed both the mean number of motor unit spikes counted and
      the mean amplitude of the spikes increased significantly (P < 0.01). This
      progressive increase in spike activity was the result of a discontinuous process
      with periods of increasing and decreasing activity. The phenomenon in which newly
      recruited motor units replace previously active units is termed "motor unit
      rotation" and appeared to be an important characteristic of motor control during
      a prolonged low level contraction. In contrast to the 10% MVC experiment, there
      was no indication of de novo recruitment in the 40% MVC experiment. Near the
      point of exhaustion a marked change in action potential shape and duration
      dominated the recordings. These findings demonstrate a conspicuous difference in
      the patterns of motor unit recruitment during a 10% and a 40% MVC sustained
      contraction. It is suggested that there is a close relationship between intrinsic
      muscle properties and central nervous system recruitment strategies which is
      entirely different in fatiguing high and low level isometric contractions.

PMID- 8299602
TI  - Skeletal muscle damage during tourniquet-induced ischaemia. The initial step
      towards atrophy after orthopaedic surgery?
AB  - Muscle biopsies from the vastus lateralis muscle of patients who had undergone
      anterior cruciate ligament surgery under conditions of tourniquet-induced
      ischaemia were examined under the electron microscope at different periods of
      time up to 90 min of ischaemia. The severity of the alterations in ultrastructure
      appeared to depend on the period of ischaemia. The pathological changes consisted
      of accumulation of lysosomes, persistent intrafibre oedema, and some
      extracellular oedema. Signs of fibre necrosis were found after 90 min of
      ischaemia. Capillary ultrastructure was only altered with regard to some swelling
      of the endothelium and marked thickening of the basement membrane. It was
      concluded that skeletal muscle could be severely affected even during relatively
      short periods of ischaemia, which might facilitate the development of muscle
      atrophy during immobilization after orthopaedic surgery.

PMID- 8299603
TI  - Circulating leucocyte subpopulations in sedentary subjects following graded
      maximal exercise with hypoxia.
AB  - Ten healthy sedentary subjects [age, 27.5 (SD 3.5) years; height, 180 (SD 5) cm;
      mass, 69.3 (SD 6.3) kg] performed two periods of maximal incremental graded cycle
      ergometer exercise in a supine position. Randomly ordered and using an open
      spirometric system, one exercise was carried out during normoxia [maximal oxygen
      consumption (VO2max) = 38.6 (SD 3.5) ml.min-1.kg-1; maximal blood lactate
      concentration, 9.86 (SD 1.85) mmol.l-1; test duration, 22.6 (SD 2.7) min], the
      other during hypoxia [VO2max = 33.2 (SD 3.2) ml.min-1.kg-1; maximal blood lactate
      concentration, 10.38 (SD 2.02) mmol.l-1; test duration, 19.7 (SD 2.8) min]. At
      rest, immediately (0 p) and 60 min (60 p) after exercise, counts of leucocyte
      subpopulations (flow cytometry), cortisol and catecholamine concentrations were
      determined. At 0 p in contrast to normoxia, during hypoxia there was no
      significant increase of granulocytes. There were no significant differences
      between normoxia and hypoxia in the increases from rest to 0 p in counts of
      monocytes, total lymphocytes and lymphocyte subpopulations [clusters of
      differentiation (CD), CD3+, CD4+CD45RO-, CD4+CD45RO+, CD8+CD45RO-, CD8+CD45RO+,
      CD3+HLA-DR+, CD3-CD16/CD56+, CD3+CD16/CD56+, CD19+] as well as adrenaline,
      noradrenaline and cortisol concentrations. The counts of CD3-CD16/CD56(+)- and
      CD8+CD45RO(+)-cells increased most. At 60 p, CD3-CD16/CD56+ and CD3+CD16/CD56(+)
      cell counts were below pre-exercise levels and under hypoxia slightly but
      significantly lower than under normoxia. We concluded that the exercise-induced
      mobilization and redistribution of most leucocyte and lymphocyte subpopulations
      were unimpaired under acute hypoxia at sea level. Reduced increases of
      granulocyte counts during the study and reduced cell numbers of natural killer
      cells and cytotoxic, not major histocompatibility complex-restricted T-cells,
      only indicated marginal effects on the immune system.

PMID- 8299604
TI  - Effects of body and head positions on bilateral difference in tympanic
      temperatures.
AB  - We have examined the nonparallel changes in tympanic membrane temperatures (Tty)
      from the two ears in response to various changes in body and head positions. Upon
      assuming a lateral recumbent position, the Tty on the lower side increased while
      that on the upper side decreased. Pressure application over a wide area of the
      lateral chest only caused inconsistent and obscure asymmetric changes in Tty. A
      lateral flexion of the head with the subject sitting upright and a rotation of
      the head to the side in a supine position induced an increase in the Tty on the
      lower side compared to that on the upper side. The temperature and blood flow of
      the forehead often decreased on the lower side and increased on the upper side,
      although such responses were not always concomitant with the asymmetric changes
      in Tty. A dorsal flexion of the head with the subject in a reclining position
      caused a slight increase in the Tty, whereas raising the head upright induced a
      slight decrease in them. Two additional experiments were carried out with single
      photon emission computed tomography using 99mTc-hexamethylpropyleneamine oxime as
      tracer, and a slight, relative decrease in counts was noted in the right
      hemisphere during rotation of the head to the right. These results would strongly
      suggest that unilateral increases and decreases in Tty could have been caused by
      one-sided decreases and increases, respectively, in blood flow to the brain
      and/or the tympanic membrane, induced by a vasomotor reflex involving vestibular
      stimulation.

PMID- 8299605
TI  - Lactate disposal in resting trained and untrained forearm skeletal muscle during
      high intensity leg exercise.
AB  - At a given oxygen uptake (VO2) and exercise intensity blood lactate
      concentrations are lower following endurance training. While decreased production
      of lactate by trained skeletal muscle is the commonly accepted cause, the
      contribution from increased lactate removal, comprising both uptake and metabolic
      disposal, has been less frequently examined. In the present study the role of
      resting skeletal muscle in the removal of an arterial lactate load (approximately
      11 mmol.l-1) generated during high intensity supine leg exercise (20 min at
      approximately 83% maximal oxygen uptake) was compared in the untrained (UT) and
      trained (T) forearms of five male squash players. Forearm blood flow and the
      venoarterial lactate concentration gradient were measured and a modified form of
      the Fick equation used to determine the relative contributions to lactate removal
      of passive uptake and metabolic disposal. Significant lactate uptake and disposal
      were observed in both forearms without any change in forearm VO2. Neither the
      quantity of lactate taken up [UT, 344.2 (SEM 118.8) mumol.100 ml-1; T, 330.3 (SEM
      85.3) mumol.100 ml-1] nor the quantity disposed of [UT, 284.0 (SEM 123.3)
      mumol.100 ml-1, approximately 83% of lactate uptake; T, 300.8 (SEM 77.7)
      mumol.100 ml-1, approximately 91% of lactate uptake] differed between the two
      forearms. It is concluded that while significant lactate disposal occurs in
      resting skeletal muscle during high intensity exercise the lower blood lactate
      concentrations following endurance training are unlikely to result from an
      increase in lactate removal by resting trained skeletal muscle.

PMID- 8299606
TI  - Reproducible increases in blood pressure during intermittent noise exposure:
      underlying haemodynamic mechanisms specific to passive coping.
AB  - The purpose of the present study was to investigate the reproducibility of the
      increases in blood pressure found in our recent study on exposure to intermittent
      noise, to confirm the haemodynamic mechanism raising blood pressure (via an
      increase in peripheral vascular resistance expected to be specific to passive
      coping), and to assess baroreceptor cardiac reflex sensitivity in connection with
      the blood pressure elevation. A group of 16 young normotensive men participated
      in the experiment and underwent a 10-min intermittent exposure to pink noise at
      100 dB (sound pressure level). The subjects also underwent three other stresses:
      a 1-min cold pressor test, a 3-min isometric handgrip and 3-min of mental
      arithmetic. The results indicated that blood pressure was elevated reproducibly
      for most of the noise exposure periods and that peripheral vascular resistance
      increased simultaneously, as expected. Baroreflex sensitivity was not suppressed.
      The results, as a whole, were in agreement with our recent findings for exposure
      to a similar type of noise and thus the reproducibility was corroborated. The
      mechanism raising blood pressure was similar in the cold pressor test.
      Conversely, during the isometric handgrip and mental arithmetic, blood pressure
      elevations were attributable mainly to increases in cardiac output. The
      implications of the opposing haemodynamic mechanisms raising blood pressure among
      the four stressful tasks have been discussed in relation to active versus passive
      coping required for each task. Differences in the magnitude of suppression
      observed in baroreflex sensitivity among the tasks have also been discussed in
      the context of defence reactions.

PMID- 8299607
TI  - Measurements of energy expenditure using isotope-labelled water (2H2(18)O) during
      an Arctic expedition.
AB  - Estimates of energy expenditure using both isotope-labelled (2H2(18)O) water and
      dietary intake/body composition changes were made during an attempt by two men
      (MS and RF) to walk to the North Pole. The isotope-labelled water technique gave
      mean estimates of daily energy expenditure for the 48-day expedition of 28.05 MJ
      (MS) and 32.38 MJ (RF), which compared with estimates of 25.66 MJ (MS) and 24.86
      MJ (RF) from the intake/body composition measurements. Fluid retention and
      peripheral oedema probably caused a considerable underestimate of the losses in
      body energy stores when applying the energy balance method, whereas in the
      isotope method, uncertainty in the measurements of isotopic background led to
      minimum errors of -4.9% to +4.0% of the means for MS and -12.7% to +8.2% for RF
      (95% confidence limits).

PMID- 8299608
TI  - Responses to whole body and finger cooling before and after an Antarctic
      expedition.
AB  - Eight subjects, who were indoor workers and not habitually exposed to cold, spent
      53 days in Antarctica. They did mainly geological field work often requiring the
      use of bare hands. The effects of the expedition on responses to a whole body
      cold exposure test, a finger blood flow test and a cold pressor test were
      studied. After the expedition, during whole-body cooling the time for the onset
      of shivering was delayed by 36 min (P < 0.001) and forearm and thigh temperatures
      were 1.5 degrees C higher (P < 0.05) at the end of exposure. During local cooling
      of the finger with 10 degrees C perfusion, finger vascular resistance was 14.9
      (SEM 6.6) mmHg.ml-1.min.100 ml (P < 0.05) lower and finger temperature 3.9 (SEM
      0.8) degrees C higher (P < 0.01). However, the decrease in rectal temperature
      during whole-body cooling was unaltered and the response to a cold pressor test
      was unchanged. The data would indicate that partial acclimatization to cold had
      been developed. Changes in forearm temperature were correlated with the duration
      of cold exposure of the hands (P < 0.05) and finger vascular resistance and
      finger temperature were correlated with responses to cooling before the
      expedition (P < 0.001 and P < 0.01, respectively). Because the ambient
      temperature was not clearly lower in Antarctica in comparison to Finland, the
      reason for the changes developed seems to be the increased exposure to the
      outdoor climate in Antarctica.

PMID- 8299609
TI  - Correlation between inflection of heart rate/work performance curve and
      myocardial function in exhausting cycle ergometer exercise.
AB  - The heart rate/work performance (fc/W) curve is usually S-shaped but a flattening
      at the top is not always seen. By means of radionuclide ventricular scintigraphy,
      the left ventricular ejection fraction (LVEF) of 15 sports students was
      investigated. The behaviour of the fc/W curve during cycle ergometry with
      increasing exercise intensities was examined. During exercise, the LVEF showed a
      distinct initial increase reaching roughly constant values at stress levels below
      maximum, and sometimes even falling again. The inflections of the fc/W curve and
      left ventricular ejection fraction/performance curve (LVEFPC) were calculated
      from a second degree polynomial fit. From this function, the slopes of the
      tangents at the points of aerobic threshold and maximum performance were
      calculated together with the differences of the angles as a measure of the fc/W
      curve and LVEFPC inflections. It follows that the fc/W curve inflection became
      less pronounced or was even absent altogether when the decrease in LVEF towards
      the end of the ergometer exercise became more distinct. A significant negative
      correlation was found between the existence and extent of the fc/W curve
      inflection and the stress-dependent myocardial function, expressed as the
      inflection of the LVEFPC (P < 0.01, r = 0.673). Thus, it would seem that the
      absence of a fc/W curve inflection was related to a diminished stress-dependent
      myocardial function.

PMID- 8299610
TI  - Myo-electric fatigue and force failure from submaximal static elbow flexion
      sustained to exhaustion.
AB  - Static contraction to the limit of endurance was performed at 40% and 10% of the
      maximal voluntary contraction (MVC). A group of 11 men (10 in their twenties, one
      aged 44) had the surface electromyogram of the brachioradialis and the biceps
      brachii (BB) muscles of the right arm (elbow angle 135 degrees) recorded.
      Endurance times were 113 (SD 28) s (40% MVC) and 51 (SD 19) min (10% MVC).
      Prolonged contraction changed the root mean square (rms) amplitude, the median
      frequency (fm), and the average muscle fibre conduction velocity (CV, measured by
      cross-correlation) as follows: 40% MVC: rms amplitude, increase of 150%-200%; fm,
      decrease of 55%-60%; CV, decrease of 25%-40%; and 10% MVC: rms amplitude,
      increase of 400%; fm, decrease of 20%; CV, decrease of 0%-10%. Since the CV of
      10% MVC changed little or not at all, the large rms amplitude increases were
      attributed to motor unit (MU) recruitment, i.e. a massively intensified central
      motor command. The relative fm decreases of both contraction levels surpassed the
      CV slowing to an extent increasing with the relative contraction time; the
      additional fm lowering was in part assumed to reflect central nervous system
      mediated regulation of the time dispersion of MU firing, principally
      synchronization/grouping of MU action potentials (AP). Electrical stimulation of
      the BB muscle and the performance of 100% MVC test contractions found uniform
      relative force failures due to the performance of 40% and 10% MVC contractions.
      From variations in amplitude and conduction time of compound action potentials
      (CAP), it seemed unlikely that reduced muscle fibre excitability/AP propagation
      failure was underlying the force losses at exhaustion. Rather, the well preserved
      CAP after 10% MVC and the recovery CAP of 40% MVC indicated excitation
      contraction failure caused by sustained voluntary contractions.

PMID- 8299611
TI  - Exogenous 13C glucose oxidation during exercise: North American vs Western
      European studies.
AB  - The purpose of this study was to test the hypothesis that the well-documented
      changes in background 13C enrichment of expired CO2 observed in response to
      exercise and carbohydrate ingestion, in subjects living on a North American diet,
      are not present in subjects living on a Western European diet. The experimental
      protocol used by Pirnay et al. in 1977 and by Krzentowski et al. in 1984 in
      subjects living on a Western European diet (4 h of exercise on a treadmill at
      approximately 50% VO2max with ingestion of 100 g of glucose in 400 ml of water)
      was duplicated as closely as possible in six subjects living on a North American
      diet. The actual amounts of exogenous glucose oxidized, computed with a high
      artificial 13C enrichment of glucose (+189.7/1000 delta 13C PDB-1) which allows
      one to neglect the 1-2/1000 delta changes in 13C background, were [mean (SEM)]
      54.7 (5.4) and 84.2 (3.4) g over 2 h and 4 h of exercise, respectively. These
      values compare well with data computed by Pirnay et al. [56.6 (13.1) and 94.9
      (4.2) g] and by Krzentowski et al. [55.0 (6.2) and 88.0 (4.5) g] using a natural
      enrichment of glucose (-11.21 and -10.63/1000 delta 13C PDB-1, respectively)
      assuming no change in 13C background in their Western European subjects. Under
      the same assumption and using a natural enrichment of glucose (-11.30/1000 delta
      13C PDB-1) the oxidation of exogenous glucose was overestimated by 30-40% in our
      North American subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299612
TI  - Ergometric and metabolic adaptation to a 5-s sprint training programme.
AB  - The effects of 7 weeks of sprint training (repeated 5-s all-out sprints) on
      maximal power output (Wv,max) determined during a force-velocity test and a 30-s
      Wingate test (Wpeak) were studied in ten students [22 (SD 2) years] exercising on
      a cycle ergometer. Before and after training, muscle biopsies were taken from
      vastus lateralis muscle at rest for the ten subjects and immediately after a
      training session for five of them. Sprint training induced an improvement both in
      peak performances by 25% (Wv,max and Wpeak) and in the 30-s total work by 16%.
      Before sprint training, the velocity reached with no load (v0) was related to the
      resting muscle phosphocreatine (PCr) stores (r = 0.87, P < 0.001). The training
      induced changes in v0 were observed only when these PCr stores were lowest. This
      pointed to a possible limiting role of low PCr concentrations in the ability to
      reach a high velocity. The improvement in performances was linked to an increase
      in the energy production from anaerobic glycolysis. This result was suggested in
      muscle by the increase in lactate production measured after a training session
      associated with the 20% higher activity of both phosphofructokinase and lactate
      dehydrogenase. The sprint training also increased the proportion of slow twitch
      fibres closely related to the decrease in fast twitch b fibres. This result would
      appear to demonstrate an appropriate adaptive reaction following high-intensity
      intermittent training for the slow twitch fibres which exhibit a greater
      oxidative capacity.

PMID- 8299613
TI  - The effects of intensity of exercise on excess postexercise oxygen consumption
      and energy expenditure in moderately trained men and women.
AB  - This experiment investigated the effects of intensity of exercise on excess
      postexercise oxygen consumption (EPOC) in eight trained men and eight women.
      Three exercise intensities were employed 40%, 50%, and 70% of the predetermined
      maximal oxygen consumption (VO2max). All ventilation measured was undertaken with
      a standard, calibrated, open circuit spirometry system. No differences in the
      40%, 50% and 70% VO2max trials were observed among resting levels of oxygen
      consumption (VO2) for either the men or the women. The men had significantly
      higher resting VO2 values being 0.31 (SEM 0.01) l.min-1 than did the women, 0.26
      (SEM 0.01) l.min-1 (P < 0.05). The results indicated that there were highly
      significant EPOC for both the men and the women during the 3-h postexercise
      period when compared with resting levels and that these were dependent upon the
      exercise intensity employed. The duration of EPOC differed between the men and
      the women but increased with exercise intensity: for the men 40%--31.2 min; 50%-
      42.1 min; and 70%--47.6 min and for the women, 40%--26.9 min; 50%--35.6 min; and
      70%--39.1 min. The highest EPOC, in terms of both time and energy utilised was at
      70% VO2max. The regression equation for the men, where y = O2 in litres, and x =
      exercise intensity as a percentage of maximum was y = 0.380x + 1.9 (r2 = 0.968)
      and for the women is y = 0.374x - 0.857 (r2 = 0.825).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8299614
TI  - Effect of antioxidant vitamin supplementation on muscle function after eccentric
      exercise.
AB  - This study investigated the effects of antioxidant vitamin supplementation upon
      muscle contractile function following eccentric exercise and was performed double
      blind. Twenty-four physically active young subjects ingested either placebo (400
      mg; n = 8), vitamin E (400 mg; n = 8) or vitamin C (400 mg; n = 8) for 21 days
      prior to and for 7 days after performing 60 min of box-stepping exercise.
      Contractile function of the triceps surae was assessed by the measurement of
      maximal voluntary contraction (MVC) and the ratio of the force generated at 20 Hz
      and 50 Hz tetanic stimulation before and after eccentric exercise and for 7 days
      during recovery. Following eccentric exercise, MVC decreased to 75 (4)% [mean
      (SE); n = 24; P < 0.05] of the preexercise values and the 20/50 Hz ratio of
      tetanic tension from 0.76 (0.01) to 0.49 (0.03) [mean (SE); n = 24; P < 0.05).
      Compared to the placebo group no significant changes in MVC were observed
      immediately post-exercise, though recovery of MVC in the first 24 h post-exercise
      was greater in the group supplemented with vitamin C. The decrease in 20/50 Hz
      ratio of tetanic tension was significantly less (P < 0.05) post-exercise and in
      the initial phase of recovery in subjects supplemented with vitamin C but not
      with vitamin E. These data suggest that prior vitamin C supplementation may exert
      a protective effect against eccentric exercise-induced muscle damage.

PMID- 8299615
TI  - Pulmonary gas exchange and breathing pattern during and after exercise in highly
      trained athletes.
AB  - Highly trained athletes (HT) have been found to show arterial hypoxaemia during
      strenuous exercise. A lack of compensatory hyperpnoea and/or a limitation of
      pulmonary diffusion by pulmonary interstitial oedema have been suggested as
      causes, but the exact role of each is not clear. It is known, however, that
      interstitial pulmonary oedema may result in rapid shallow breathing (RSB). The
      purpose of this study was therefore twofold: firstly, to determine the exact role
      of a lack of compensatory hyperpnoea versus a widened in ideal alveolar minus
      arterial oxygen partial pressure difference [PA(i)-aO2] in the decrease in
      partial pressure of oxygen in arterial blood (PaO2) and, secondly, to detect RSB
      during recovery in HT. Untrained subjects (UT) and HT performed exhausting
      incremental exercise. During rest, exercise testing, and recovery, breathing
      pattern, respiratory gas exchange, and arterial blood gases were measured. The
      PA(i)-aO2 and the difference in tidal volume (VT) between exercise and recovery
      for the same level of ventilation, normalized to vital capacity of the subject
      [delta VT(%VC)], were then calculated. A large positive delta VT(%VC) was
      considered to be the sign of RSB. HT showed a marked hypoxaemia (F = 11.6, P <
      0.0001), higher partial pressure of carbon dioxide in arterial blood (F = 3.51, P
      < 0.05), and lower ideal partial pressure of oxygen in alveolar gas (P < 0.001).
      The relationship between PA(i)-aO2 and oxygen consumption was the same for the
      two groups. The widening PA(i)-aO2 persisted throughout recovery for both HT and
      UT. The RSB was observed in HT during recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299616
TI  - Effects of acclimatization to cold baths on men's responses to whole-body cooling
      in air.
AB  - The purpose of this study was to investigate the thermoregulatory mechanisms
      underlying artificial acclimatization to cold and to compare them with those of
      naturally acclimatized men. Six white men were cooled, nude, in air at 10 degrees
      C for 2 h before and after they had been acclimatized by ten daily cold (15
      degrees C) baths of 30-60 min followed by rapid rewarming in hot (38-42 degrees
      C) water, and again 4 months later after acclimatization had decayed. Six control
      subjects also underwent the same tests, providing an opportunity to discriminate
      between changes caused by the immersions and those caused by extraneous
      influences. Acclimatization significantly reduced heat production and heat loss
      (P < 0.05) but did not change heat debt. The reduced heat production was
      accompanied by reductions in shivering (P < 0.10) and in cold-induced muscle
      tenseness; no evidence of nonshivering thermogenesis or active brown fat was
      found. These findings are attributed to increased tissue insulation, mediated by
      an enhanced vascular response to cold that did not involve the cutaneous
      circulation and was probably located in skeletal muscle. Thermal sensation and
      discomfort did not change, although perceived strain tended to increase (P =
      0.08). Acclimatization was accompanied by, but was unrelated to, slower cooling
      of the finger and toe. The main conclusions, and many specific findings, agree
      with those of two previous studies made by the same techniques in naturally
      acclimatized men wintering in Antarctica. Other significant findings included
      changes--in particular reduced thermoneutral rectal temperature and a delayed
      onset of shivering--that are commonly regarded as evidence of acclimatization but
      were in fact unrelated to it as they also occurred in the control group. They are
      attributed to extraneous influences, in particular the relaxation of heightened
      arousal ('first-time effects') found in the baseline tests.

PMID- 8299617
TI  - Cardiovascular and metabolic responses to noradrenaline in men acclimatized to
      cold baths.
AB  - The purpose of this study was to see whether artificial acclimatization to cold
      would reduce the pressor response to noradrenaline (NA) as natural
      acclimatization has been shown to do, and whether it would induce nonshivering
      thermogenesis. Three white men were infused with NA at four dosage levels between
      0.038 and 0.300 microgram.kg-1.min-1 (2-23 micrograms.min-1), before and after
      artificial acclimatization to cold and again 4 months later when acclimatization
      had decayed. Acclimatization was induced by ten daily cold (15 degrees C) baths
      of 30-60 min followed by rapid rewarming in hot (38-42 degrees C) water, and was
      confirmed by tests of the subjects' responses to whole-body cooling in air. Three
      control subjects also underwent the first and third tests. Acclimatization
      substantially reduced the pressor response to NA at 0.150 and 0.300 micrograms.kg
      1.min-1, confirming earlier findings by the same technique in naturally
      acclimatized men, and its decay increased this response to beyond its initial
      levels (P < 0.05 for both changes). Acclimatization did not change the response
      to NA of heart rate, subjective impressions, skin temperature of finger and toe,
      pulmonary ventilation, or plasma free fatty acids and ketone bodies. At no time
      did NA increase oxygen consumption, or increase skin temperature or heat flow
      over reported sites of brown fat. These findings would seem to show that
      acclimatization to cold reduces sensitivity to the pressor effect of NA but does
      not induce nonshivering thermogenesis, and that the reduced sensitivity is
      replaced by a hypersensitivity to NA when acclimatization decays.

PMID- 8299618
TI  - Effect of electrical stimulation training on the contractile characteristics of
      the triceps surae muscle.
AB  - This study aimed to assess the effects of training using electrical stimulation
      (ES) on the contractile characteristics of the triceps surae muscle. A selection
      of 12 subjects was divided into two groups (6 control, 6 experimental). The ES
      sessions were carried out using a stimulator. Flexible elastomer electrodes were
      used. The current used discharged pulses lasting 200 microseconds at 70 Hz.
      Contraction time was 5 s and rest time 15 s. The session lasted 10 min for each
      muscle. Training sessions were three times a week for 4 weeks. Biomechanical
      tests were performed using an isokinetic ergometer. Subjects performed plantar
      flexions of the ankle over a concentric range of movement at different angular
      velocities (60, 120, 180, 240, 300, 360 degrees.s-1) and held isometric
      contractions for 5 s at several ankle flexion angles (-30/-15/0/15 degrees-0
      corresponded to foot flexion of 90 degrees relative to the leg axis). The force
      velocity relationship was seen to shift evenly upwards under the influence of ES
      (P < 0.05). The increased force during the "after" test was greater (P < 0.05)
      for ankle angle positions of 15 degrees and -30 degrees, which demonstrated a
      link between the training angle and the gain in strength. No change was noted in
      the cross-sectional area of the muscle. The results showed that ES allowed the
      contractile qualities of muscle to be developed in isometric and dynamic
      conditions. Nervous mechanisms can account for most of these adaptations.

PMID- 8299619
TI  - Twitch interpolation technique in testing of maximal muscle strength: influence
      of potentiation, force level, stimulus intensity and preload.
AB  - The aim was to study the methodological aspects of the muscle twitch
      interpolation technique in estimating the maximal force of contraction in the
      quadriceps muscle utilizing commercial muscle testing equipment. Six healthy
      subjects participated in seven sets of experiments testing the effects on twitch
      size of potentiation, time lag after potentiation, magnitude of voluntary force,
      stimulus amplitude, stimulus duration, angle of the knee, and angle of the hip.
      In addition, the consequences of submaximal potentiation on the estimation of
      maximal force from twitch sizes were studied in five healthy subjects. We found
      an increase in twitch size with increasing levels of potentiation and twitch size
      decreased exponentially following potentiation. We found a curvilinear
      relationship between twitch size and voluntary force, and these properties were
      more obvious when the stimulation intensity of the preload was reduced. The
      relationship between twitch size and force was only linear, for force levels
      greater than 25% of maximum. It was concluded that to achieve an accurate
      estimate of true maximal force of muscle contraction, it would be necessary for
      the subject to be able to perform at least 75% of the true maximal force.

PMID- 8299620
TI  - Shoulder muscle load and muscle fatigue among industrial sewing-machine
      operators.
AB  - Physiological responses to physical work were assessed for 29 female industrial
      sewing-machine operators during an 8-h working day under ordinary working
      conditions. During sewing-machine work, the average (left and right) static load
      in the trapezius muscle was 9% of the maximal electromyogram (EMG) amplitude (%
      EMGmax), while the average mean load was 15% EMGmax, and the average peak load
      was 23% EMGmax. The static load level was unrelated to the muscle strength of the
      sewing-machine operators, which for the group as a whole was within the normal
      range. The load levels remained unchanged during the working day, while changes
      in the EMG mean power frequency and zero crossing frequency rate occurred, both
      indicating the development of muscle fatigue in left and right trapezius muscle
      during the working day. In line with this, the rating of perceived exertion in
      the shoulder and neck region increased during the working day. Dividing the group
      of sewing-machine operators into two groups, those with the highest frequency and
      those with the lowest frequency of shoulder/neck troubles showed that the former
      group had significantly lower muscle strength, despite the fact that no
      differences in the surface EMG during sewing were found between the two groups.
      It was concluded that industrial sewing-machine work involves a pattern of
      shoulder muscle activity which induces fatiguing processes in the shoulder and
      neck regions. Furthermore, since the static shoulder muscle load was independent
      of muscle strength, factors other than working posture may be of significance for
      the static shoulder muscle load.

PMID- 8299621
TI  - Neuromuscular responses of elderly women to tasks of increasing complexity
      imposed during walking.
AB  - The purpose of this electromyographic study was to examine the effects of age on
      lower limb muscle response characteristics during reaction tasks of varying
      complexity when standing and walking. Ten young (mean age 22 years) and ten
      elderly (mean age 68 years) women participated in the investigation. No
      differences between groups were recorded in muscle activation times (MAT) in
      response to a visual light directional stimulus (LDS) during all standing
      reaction tasks. All the women required a longer period of time to respond to LDS
      when walking than standing. Completion of complex walking reaction tasks produced
      significantly longer (P < 0.001) MAT in all subjects than the more simple walking
      reaction tasks. Delays in neuromuscular response were significantly greater (P <
      0.05) in the older women as the complexity of the walking reaction task
      increased. Movement behaviour of subjects during the walking reaction trials
      suggested that relatively greater demands were placed on the neuromuscular
      systems of the elderly during those tasks of greatest complexity. It was
      postulated that these movements were directed more at compensating for a reduced
      neuromuscular ability to control efficiently balance homeostasis. The results of
      this study provide further support for the hypothesis that delays in the central
      processing of information during reaction tasks may occur with ageing.

PMID- 8299622
TI  - Long-term comprehensive cardiac care--the perspectives and tasks of cardiac
      rehabilitation.
AB  - Restoration of the patient's physiological, psychological and social capabilities
      should improve the quality of survival. It is paramount that a multifactorial
      disease is treated by a multifactorial approach. Until the end of the 1960s
      rehabilitation was identified with physiotherapy and physical training. It was
      only during the past two decades that a comprehensive long-term approach was
      systematically accepted, mainly that physical training is only one therapeutic
      modality which can be applied in selected groups of coronary patients, and that
      rehabilitation procedures must include risk factor modifications, change in life
      habits, and other conservative and/or surgical therapeutic measures. In
      programmes which are conducted under directed supervision, either in specific
      cardiac rehabilitation units, or under clinical conditions (particularly in the
      early rehabilitation phase II), one of the most important goals of CCC is close
      follow-up, which enables the early detection of deterioration and timely
      initiation of effective therapeutic measures. Randomized trials have so far
      produced some meaningful results concerning mortality, while non-randomized
      controlled trials have also shown a lower mortality in intervention groups.
      Rehabilitation programmes have to be considered as an integral part of CCC. The
      early initiation of such comprehensive interventions in the acute phase I,
      convalescent phase II and maintenance phase III after myocardial infarction may
      have contributed to the decline in mortality in some countries. Quality of
      survival can certainly be enhanced by comprehensive rehabilitation; whether or
      not survival itself can be influenced still remains to be demonstrated.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8299623
TI  - Family history as an independent risk factor for ischaemic heart disease in a low
      incidence area (Galicia, Spain).
AB  - It has been suggested that a family history positive for coronary heart disease
      (CHD) increases the risk of CHD. We studied this association to determine the
      degree of risk, the independence of this association and the presence of
      interaction of a family history of CHD with the major known risk factors in a low
      incidence area. One hundred and six hospital cases (85 males and 21 females) of
      CHD and 106 hospital controls individually matched with each case for sex, age
      and place of residence (rural-urban) were studied. From every participant,
      information was collected on their personal and family history of cardiovascular
      disease and risk factors; height, weight, lipid profile and blood pressure were
      measured, and an electrocardiogram was recorded. Conditional logistic regression
      was used in the analysis. The observed odds ratio of patients suffering from CHD
      among those with, compared to those without, a positive family history of CHD was
      4.95 (95% confidence interval = 1.27-19.28) after adjusting for the major known
      risk factors in each individual and their families (no interaction term remained
      in the model). The results support the hypothesis that a family history of CHD,
      acting through mechanisms other than known risk factors or their familial
      aggregation, is an independent risk factor for CHD even in a low incidence area.
      No interaction effect was observed between family history and the presence of the
      three major risk factors of CHD. This should help to identify individuals at
      greater risk of CHD.

PMID- 8299624
TI  - The role of anticoagulation in the development of pericardial effusion and late
      tamponade after cardiac surgery.
AB  - This study aimed at elucidating the role of anticoagulation in the genesis of
      late pericardial effusion and tamponade after cardiac surgery. Using serial 2-D
      echocardiography, 141 patients undergoing surgery for coronary artery bypass
      (56), valvular (69) or congenital (16) [corrected] heart disease were studied
      postoperatively. Group 1 (74 patients) received full anticoagulation (warfarin
      73; heparin 1) and group 2 (67 patients) received either antithrombotic agents
      (aspirin plus dipyridamole), or no treatment. Fifty percent (70/141) of patients
      developed effusion. There was no significant difference between the two groups in
      the incidence of either effusion in general (43/74; 58% vs 27/67; 40%,
      respectively) or small or medium sized effusion. However, a large effusion was
      significantly more common in group 1 than in group 2 (32% vs 4%, P < 0.005).
      Twelve patients (12/141; 8.5%) developed late tamponade, 7 to 33 (15 +/- 7.3 mean
      +/- SD) days after surgery. All had a large effusion demonstrated by echo,
      drained by pericardiocentesis, and none died. All 12 patients with tamponade
      belonged to group 1 (P < 0.001). Excess anticoagulation was detected at least
      once in 41 of the 74 group 1 patients (55%). When compared to properly
      anticoagulated patients, excessively anticoagulated patients had a similar
      overall incidence of effusion and a similar incidence of small or moderate
      effusion, but a higher incidence of large effusion (18% vs 44%, [corrected] P <
      0.05) and tamponade (3% vs 27%, P < 0.025). We conclude that, unlike small or
      medium-sized effusions, large pericardial effusions and tamponade are more likely
      to occur among anticoagulated patients, especially if they are excessively
      anticoagulated.

PMID- 8299625
TI  - Williams-Beuren syndrome: a 30-year follow-up of natural and postoperative
      course.
AB  - One hundred and four patients with Williams-Beuren syndrome were investigated
      from 1958 to 1992. Follow-up ranged from 1 to 32 years (mean 13), during which
      time 10 patients died and 17 were lost to follow-up. Seventy-six patients were in
      NYHA classes I and II and one was in class III. When first investigated, blood
      pressure was raised in 82% of the patients; at the latest evaluation 52% suffered
      from high blood pressure. Right heart catheterization was performed in 100
      patients and repeated in 19; left heart catheterization was performed in 85
      patients and repeated in 21. Right ventricular pressure ranged from 20 to 140
      mmHg (mean 45), the mean pressure decreased from 66 mmHg to 50 mmHg (P < 0.006),
      the average value of the 19 patients in whom the measurements were repeated. The
      supravalvular aortic gradients ranged from 0 to 110 mmHg (mean 27), and the mean
      value of the 21 patients with repeated catheterization increased from 13 to 27
      mmHg (P < 0.03). Twenty-nine patients underwent operative repair, two patients
      died peri-operatively. Pre-operative aortic gradients ranged from 40 to 110 mmHg
      (mean 76), postoperative gradients from 0 to 90 mmHg (mean 15). Forty-one adult
      patients were reevaluated. Doppler investigation revealed mild aortic
      insufficiency in eight patients and severe mitral regurgitation in one. In 32
      patients, bicycle exercise testing was normal.

PMID- 8299626
TI  - Aortic distensibility and left ventricular structure and function in isolated
      systolic hypertension.
AB  - Aortic mechanical properties were assessed in a group of elderly subjects with
      untreated isolated systolic hypertension using two-dimensional echocardiography.
      Echocardiographic (two-dimensional and Doppler) assessment of left ventricular
      structure and function was also made. Ten subjects (mean age 71.7 +/- 1.9 years,
      20% male, mean clinic blood pressure 163.6/79.2 +/- 1.2/2.0 mmHg) were compared
      with 16 normotensive subjects of similar age (69.4 +/- 1.6 years, 38% male, mean
      clinic blood pressure 129.8/78.2 +/- 3.2/2.9 mmHg). Aortic distensibility at the
      level of the transverse aortic arch was significantly reduced among subjects with
      isolated systolic hypertension. The thickness of the interventricular septum was
      approximately 20% greater in the hypertensive subjects (P < 0.01) and the average
      wall thickness to radius ratio was increased by 30%. Patterns of transmitral
      diastolic flow were also different in subjects with isolated systolic
      hypertension. Deceleration time was significantly greater (P < 0.01) and the
      ratio of early to late transmitral diastolic peak flow velocities was
      significantly less in the hypertensive (P < 0.05) than in the normotensive group.
      Left ventricular systolic function was well preserved. These findings are
      consistent with the suggestion that isolated systolic hypertension represents a
      state of increased aortic stiffness which may contribute to the development of
      left ventricular hypertrophy. Whether this increase in aortic stiffness is the
      cause or effect of the elevated systolic blood pressure remains unresolved.

PMID- 8299627
TI  - Prognostic significance of silent myocardial ischaemia during maximal exercise
      testing after a first acute myocardial infarction.
AB  - Clinical, exercise, and angiographic variables, and long-term follow-up were
      compared in patients, who, during maximal Bruce exercise testing after a first
      acute myocardial infarction (AMI), had positive responses to exercise testing (n
      = 116, 38% of 303) with (n = 23, group I) or without (n = 93, group II) angina.
      Group I patients more often (52 vs 19%, P < 0.001) had a history of pre
      infarction angina. Group II had a greater proportion (75 vs 52%, P < 0.05) of
      inferior wall AMI, whereas group I had a greater proportion (30 vs 19%, P < 0.01)
      of non-Q wave AMI. Total exercise duration was significantly (P < 0.01) longer in
      group II (7.6 +/- 3.2 vs 5.5 +/- 3.1 min). Maximal exercise heart rate (144 +/-
      22 vs 133 +/- 21, beats.min-1 P < 0.05) was also higher in group II. A greater
      proportion of group II patients (37 vs 9%, P < 0.05) had single-vessel disease,
      whereas multivessel disease was more common (91 vs 63%, P < 0.03) in group I.
      Left ventricular function was similar in both groups. During follow-up (48 +/- 22
      months) the incidence of cardiac death (group I, 3.3%, group II, 4.8%), of
      recurrent infarction (group I, 4.8%, group II 3.3%), and of revascularization
      procedures (group I, 28.5%, group II, 19.8%) were similar in both groups.
      Although asymptomatic exercise-induced ischaemia was associated with better
      exercise performance and less extensive coronary disease than symptomatic
      ischaemia, it had the same long-term prognostic implications.

PMID- 8299628
TI  - Parapharyngeal space lesions syncope-syndrome. A newly proposed reflexogenic
      cardiovascular syndrome.
AB  - An intense vaso-vagal reaction characterizes those reflex cardiovascular syncopes
      in which the glossopharyngeal nerve constitutes the main afferent nerve pathway.
      In these syndromes, afferent fibres of the glossopharyngeal nerve project from
      the baroreceptorial area to the medullary cardiac and vasomotor centres, from
      which efferent fibres descend into the vagus. The most common reflex
      cardiovascular syndromes linked to the IX nerve are carotid sinus syndrome (CSS)
      and glossopharyngeal neuralgia-asystole syndrome (GNS). Eleven male patients
      (mean age 65.4 years) with recurrent and severe vaso-vagal attacks are described.
      The episodes were characterized by asthenia and general malaise, pallor,
      sudation, unrecordable or very low (40-60 mmHg) arterial blood pressure, mental
      disorientation and/or syncope. The admission diagnosis in these patients was CSS,
      but the clinical picture was quite different from classic CSS: triggering factors
      were not present, vasovagal episodes were longer, syncopes were more frequent and
      severe and VVI pacing was ineffective. Further investigation, including
      computerized tomography, showed in all patients a malignant or benign
      pathological growth occupying and compressing the parapharyngeal space. The
      authors think that the symptoms exhibited by their patients may be attributed to
      parapharyngeal space involvement. The pathogenetic mechanism of syncope in these
      cases could be similar to that occurring in GNS except for the absence of
      neuralgia itself. Surgical carotid sinus denervation or A-V sequential DDD pacing
      were ineffective in completely controlling symptoms. Intracranial section of the
      IX nerve appears to be the most effective mechanism for controlling the
      syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299629
TI  - Metabolic responses to graded exercise in chronic heart failure.
AB  - To determine if exercise intolerance and fatigue in chronic heart failure could
      be exacerbated by an abnormal metabolic response to exercise, we studied 12
      patients with stable chronic heart failure and 12 normal volunteers during
      symptom-limited maximal treadmill exercise. Peak VO2 was 17.2 (15.1-19.2) ml.kg-1
      x min-1 in patients and 29.9 (26.3-33.5) in controls (mean and 95% confidence
      intervals; P < 0.0001, t-test). Overall, levels in peripheral venous blood of
      glucose, glycerol and free fatty acids were greater in patients, although the
      differences became less marked with increasing exercise intensity. Noradrenaline
      was elevated in patients at rest, but the peak exercise response was similar to
      controls. Responses of adrenaline, insulin and glucagon were similar in both
      groups. We conclude that depletion of the levels of circulating substrates is not
      contributory to exercise intolerance and fatigue in chronic heart failure.
      Greater levels of glycerol and free fatty acids may be mediated by excess
      sympathetic nervous system activity, reflected in elevated noradrenaline levels.

PMID- 8299630
TI  - Left ventricular thrombosis and arterial embolism after thrombolysis in acute
      anterior myocardial infarction: predictors and effects of adjunctive
      antithrombotic therapy.
AB  - The prevalence of left ventricular (LV) thrombosis and incidence of arterial
      embolism after acute anterior myocardial infarction (AAMI) treated with
      streptokinase 1.5 x 10(6) IU intravenously was studied in 136 patients enrolled
      consecutively in five cardiological centres. Adjunctive antithrombotic therapy
      was administered according to the routine of each centre. Thrombus formation was
      studied by two-dimensional echocardiography, and events of arterial embolism
      recorded. LV thrombosis was found in 37 (27.2%) of the patients. In a subgroup of
      53 patients receiving post-thrombolytic therapy with acetylsalicylic acid only, a
      thrombus developed in 14 (26.4%). The thrombus prevalence among patients given
      high-dose heparin was significantly lower than among those receiving either low
      dose heparin or no heparin (4/30 vs 33/106, P = 0.045). Logistic regression
      analysis suggested that severe LV wall motion abnormality (P < 0.001) and
      avoidance of treatment with high-dose heparin (P = 0.023) were independent
      predictors of LV thrombus formation. Only one patient (0.7%) suffered arterial
      embolism (ischaemic stroke). In conclusion, LV thrombosis is frequent after
      thrombolytic therapy for AAMI, and impaired LV wall motion represents an
      independent predisposing factor. Low-dose heparin and acetylsalicylic acid seem
      less effective for LV thrombus prophylaxis than high-dose heparin. The incidence
      of arterial embolism is low.

PMID- 8299631
TI  - Evidence of oxidative stress in chronic heart failure in humans.
AB  - Chronic heart failure (CHF) due to coronary artery disease (CAD) has been shown
      to be associated with increased plasma thiobarbituric reactive substances (TBARS)
      and reduced plasma thiol (PSH) concentrations, suggesting oxidative stress (OS).
      The aims of the present studies were (a) to determine whether OS is due to CAD or
      CHF per se and (b) to determine if a wider range of more specific markers of OS
      are abnormal in CHF. In the first study, two groups of patients (n = 15 each)
      were compared. Group 1 (11 male, mean age 56 years) had CHF due to CAD and group
      2 (12 male, mean age 53 years) had non-CAD CHF. Median plasma TBARS in controls
      was 7.6 nmol.ml-1, 10.0 nmol.ml-1 in group 1 and 9.3 nmol.ml-1 in group 2 (P <
      0.01 both groups vs control). Median PSH was 505 384 and 364 nmol.ml-1 (P < 0.05
      and P < 0.01 vs control) respectively. Fifty-three patients with CHF were
      recruited in the second study. Malondialdehyde and PSH were 10.3 and 409 nmol.ml
      1 respectively, compared to control values of 7.9 and 560 nmol.ml-1 (both P <
      0.001). The median values for the following additional measures of OS in controls
      and patients were: erythrocyte superoxide dismutase 131 vs 114 U.l-1 (P = 0.005);
      caeruloplasmin oxidase 97 vs 197 U.l-1 (P < 0.01); erythrocyte glutathione 1.56
      nmol.ml-1 vs 1.77 nmol.ml-1 (P < 0.02); plasma conjugated dienes 0.28 vs 0.33
      optical density units (P = ns).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299632
TI  - The effectiveness of beta-blockade and its influence on heart rate variability in
      vasovagal patients.
AB  - The aim of this study was to assess the effectiveness of chronic medical
      treatment with oral propranolol and its influence on heart rate variability in
      patients with vasovagal syndrome. A spectral frequency domain analysis was used
      for the estimation of heart rate variability characteristics. Thirty-six
      patients, mean age 49 +/- 17 years, with a history of recurrent syncope and
      positive tilt testing were involved in the study. All patients received oral
      propranolol (five patients also had a dual chamber inhibited DDI pacemaker
      implanted) for a mean time 12 +/- 6 months. One patient complained of syncope
      during this follow-up. The tilt test repeated in 29 patients during follow-up was
      negative in 28. In 20 patients treatment was discontinued for 4 days and a new
      tilt test was then performed. Eleven of these 20 patients (55%) had a positive
      test (P < 0.001 compared with the group in which treatment was continued). In the
      group of 11 patients in whom the tilt test became positive again after medical
      treatment had been withdrawn (mean age 43 +/- 20 years) and in 11 asymptomatic
      controls (mean age 52 +/- 19 years), with no history of syncope and negative tilt
      testing, the heart rate variability was assessed. The increase in the low
      frequency component from rest to the maximum value of heart rate variability
      during tilt testing was higher in the vasovagal group than in the controls (2.6
      +/- 1.2 vs 1.5 +/- 0.7 P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299633
TI  - Atrial peptides, ANP(1-98) and ANP(99-126) in health and disease in an elderly
      population.
AB  - Circulating immunoreactive atrial natriuretic peptide, IrANP(99-126) and the N
      terminal fragment of the prohormone, IrANP(1-98) were measured in two population
      samples from the general population of Gothenburg, Sweden. A group of 85-year
      olds (974 subjects) and a group of 40-year olds (191 subjects) were investigated
      in respect of cardiovascular, renal and metabolic disease. IrANP(99-126) and
      IrANP(1-98) were significantly higher in the 85-year olds compared to the 40-year
      olds, and were significantly increased in subjects with congestive heart failure,
      ischaemic heart disease, atrial fibrillation and renal dysfunction but not in
      subjects with hypertension. Eighty-five-year-old subjects who were on treatment
      with digitalis, beta-adrenergic-blockers, nitrates and diuretics had
      significantly increased IrANP(99-126) and IrANP(1-98). In multivariate analysis
      IrANP(99-126) concentrations were predictive for congestive heart failure,
      ischaemic heart disease, atrial fibrillation and treatment with beta-blockers and
      anti-depressant drugs. IrANP(1-98) was predictive for congestive heart failure,
      ischaemic heart disease, atrial fibrillation, diabetes mellitus, renal failure
      and drug treatment with beta-blockers and neuroleptics. We conclude that
      measurements of circulating concentrations of IrANP(99-126) and/or IrANP(1-98)
      may add valuable information in the diagnosis of congestive heart failure and
      ischaemic heart disease in an elderly population. It remains to be determined
      whether routine measurements of circulating IrANP (99-126) and IrANP(1-98) may be
      of value in predicting current cardiovascular disease for the individual patient.

PMID- 8299634
TI  - Cinefluoroscopic identification of Bjork-Shiley prosthetic heart valves.
AB  - Numerous mechanical prostheses are currently utilized for heart valve
      replacement. Fluoroscopy is a useful technique to identify prosthetic valves, to
      evaluate their function and to follow-up the patients' condition. Scattered and
      contrasting data, however, have been reported about the radiographic appearance
      of Bjork-Shiley heart valves. This study shows that each Bjork-Shiley valve model
      has characteristic radiographic features that can be readily determined by
      fluoroscopic evaluation, leading to easy and accurate non-invasive
      identification.

PMID- 8299635
TI  - Valsalva manoeuvre in the assessment of baroreflex sensitivity in patients with
      coronary artery disease.
AB  - The overshoot rise in arterial pressure after release of Valsalva strain is a
      natural challenge for baroreflex regulation of heart rate. To assess the
      feasibility of the Valsalva manoeuvre in the determination of baroreflex
      sensitivity (BRS), we measured the slope of the linear relationship between the
      length of the RR interval and preceding systolic blood pressure value during the
      overshoot phase after the strain and compared this index of BRS to a standard
      phenylephrine test in 64 subjects, of whom 58 had coronary artery disease. The
      BRS slopes obtained with the Valsalva manoeuvre showed a good linear correlation
      with the phenylephrine test (r = 0.77 in the 27 patients with two Valsalva and
      phenylephrine tests and r = 0.56 in the whole cohort). The correlation
      coefficients of the BRS slopes were better than in the phenylephrine test (r =
      0.89 vs r = 0.85, P < 0.05). The rise in systolic blood pressure in the slope
      calculation area was higher than with phenylephrine (41 +/- 18 vs 30 +/- 10 mmHg,
      P < 0.01). The reproducibility of BRS slopes in successive tests was comparable
      with both methods. These results suggest that non-invasive assessment of BRS
      using Valsalva strain to induce blood pressure rise is possible in patients with
      coronary artery disease.

PMID- 8299636
TI  - Magnetic resonance assessment of the pulmonary arterial trunk anatomy, flow,
      pulsatility and distensibility.
AB  - We used magnetic resonance imaging with cine velocity mapping to study the
      anatomy of pulmonary bifurcation and to measure volume blood flow, pulsatility of
      flow and arterial wall distensibility in the central pulmonary arteries of nine
      healthy volunteers. Multislice, multiplane spin echo images were acquired to
      display pulmonary bifurcation anatomy. Diameters of the main pulmonary artery
      (MPA) in systole were 2.56 +/- 0.35 cm and in diastole 2.20 +/- 0.33 cm. Those of
      the right pulmonary artery (RPA) were 1.57 +/- 0.29 cm and 1.39 +/- 0.23
      respectively, and of the left pulmonary artery (LPA) 1.79 +/- 0.26 cm and 1.55 +/
      0.10 cm respectively. A gradient echo sequence with phase shift velocity mapping
      was then used to measure flow in MPA, RPA and LPA 2 cm on either side of the
      pulmonary bifurcation. Time averaged flow, calculated from mean velocity and the
      cross-sectional area of the vessels was 4.99 +/- 1.10 l.min-1 in MPA, 2.23 +/-
      0.58 l.min-1 in RPA and 2.31 +/- 0.63 l.min-1 in LPA. The pulsatility index of
      flow derived from peak forward flow, peak backward flow and time averaged flow
      were as follows: MPA 4.4 +/- 0.8, RPA 5.1 +/- 0.6 and LPA 4.6 +/- 1.5.
      Distensibility, calculated from the change in cross-sectional area between
      diastole and systole and expressed as percentage were as follows: MPA 25.6 +/-
      10.7, RPA 21.4 +/- 10.7 and LPA 24.5 +/- 7.8. MRI with velocity mapping
      accurately characterized anatomy, flow, distensibility and pulsatility of the
      central pulmonary arteries.

PMID- 8299637
TI  - Double-blind randomized trial of alteplase versus placebo in patients with chest
      pain at rest.
AB  - Patients who have chest pain occurring at rest are at a significant risk of
      myocardial infarction and or sudden death. Most trials enter patients with
      anginal rest pain after an initial screening period. Thus, the clinical efficacy
      of early thrombolytic treatment for patients with rest pain remains unproven.
      Eighty patients with chest pain at rest and with ECG changes of ST depression of
      at least 1 mm in any ECG lead, were randomized to alteplase 100 mg infused over 3
      h, or placebo. Concomitantly, all patients received intravenous heparin and 300
      mg of aspirin daily (unless contra-indicated). Seventy-four patients had coronary
      angiography (the majority within 72 h of admission) of which 73 were assessable.
      The patency of the ischaemia-related vessel was not significantly greater in the
      alteplase treated group (81% vs 78%, P = 0.82). The culprit lesion morphology
      tended to be more concentric in the alteplase treated group (84% vs 56%, P =
      0.06) although alteplase treatment was not associated with a significant
      reduction in the severity of the culprit lesion stenosis. Intra-coronary thrombi
      were detected in 7% of patients (3% placebo, 11% alteplase, P = 0.35). The mean
      left ventricular ejection fraction or the alteplase-treated group was 49 +/- 3%
      and for the placebo-treated patients 56 +/- 3% (P = 0.05). There was no
      difference in the total in-hospital cardiac event rate i.e. cardiac death,
      myocardial infarction and coronary revascularization between patients receiving
      alteplase (10%, 63%, and 38%) and those receiving placebo (8%, 65%, and 30%)
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299638
TI  - Heparin after angioplasty: an unresolved issue?
AB  - Restenosis following coronary angioplasty remains a significant problem.
      Experimental work suggests that appropriate use of heparin may be beneficial
      through inhibition of smooth muscle cell proliferation. Possible mechanisms of
      this effect in various models, are discussed. Limited clinical studies to date,
      however, have failed to show therapeutic efficacy. Possible reasons for this lack
      of effect are discussed and the importance of assessing heparin in appropriate
      clinical trials is emphasized.

PMID- 8299639
TI  - High blood pressure and ventricular arrhythmias.
AB  - Here we review the blood pressure-ventricular arrhythmia relationship. An
      increase in blood pressure, by any means, may induce ventricular arrhythmias both
      experimentally and in patients with a history of ventricular ectopic beats.
      Conversely, a decrease in blood pressure may eliminate ventricular arrhythmias
      due to other causes. The increased pressure is sensed in the ventricles. Both
      systolic and diastolic loading may induce important electrophysiological changes.
      However, an increase in systolic pressure may induce ventricular ectopy even
      though the left atrial pressure remains low; on the other hand, raising the
      atrial pressure does not induce ectopic rhythms unless associated with an
      increase in arterial pressure. This phenomenon (mechanoelectrical association or
      contraction-excitation feedback) seems to be a direct one not mediated by either
      ischaemia or adrenergic stimulation. Both refractoriness and intraventricular
      conduction are affected by mechanical loading, although the direction of change
      depends on several factors. The mechanism of pressure-related arrhythmias remains
      obscure. Triggered activity due to early after-depolarizations is one
      possibility. Ventricular arrhythmias observed in chronic hypertension might be a
      clinical manifestation of mechano-electrical association, especially when they
      occur in conjunction with acute blood pressure elevations. Several
      antihypertensive agents with different mechanisms of action also have an
      antiarrhythmic effect. Extensive research to establish the antiarrhythmic
      effectiveness of antihypertensive treatment in cases with ventricular arrhythmias
      is still warranted.

PMID- 8299640
TI  - Contractile function of right ventricular papillary muscle after left ventricular
      infarction in rats: effects of early and late inhibition of angiotensin
      converting enzyme.
AB  - Alterations in the right ventricular function may or may not contribute to
      progressive cardiac dysfunction after left ventricular infarction. Ligation of
      the left coronary artery (LCAL) was lethal within 24 h for 25% of 100 rats,
      whereas none of 21 sham-operated rats died. No rats died during the following 4
      weeks, after which the ischaemic area of the left ventricular wall appeared
      fibrotic and weighed 0.041% of the body weight. Simultaneously, the weight of the
      right ventricle increased from 0.037 to 0.072% of the body weight. The
      hypertrophied right papillary muscle had a depressed force of contraction and
      prolonged contraction and relaxation phases. Angiotensin converting enzyme
      inhibition (ACEI) started early (24 h) prevented hypertrophy and normalized the
      contractile pattern under basic conditions. However, isoprenaline stimulation
      revealed that the relaxation phase was still prolonged. Concentration-effect
      curves for Ca2+ indicated that the pathological relaxation observed in the
      hypertrophied muscles and during isoprenaline stimulation of myocardium in ACEI
      treated animals could be due to insufficient re-uptake of cytosolic Ca2+ by the
      sarcoplasmic reticulum. The results support the idea that the development of
      right ventricular hypertrophy may contribute to pathophysiological consequences
      of an infarct in the left ventricle. ACEI started after 24 h prevented
      hypertrophy, whereas ACEI started after 14 days did not. ACEI was unable to
      normalize completely the balance between energy demand and energy delivery.

PMID- 8299641
TI  - Increased dispersion of ventricular repolarization and ventricular
      tachyarrhythmias in the globally ischaemic rabbit heart.
AB  - Contemporary concepts of ischaemic ventricular tachyarrhythmias (VTA) are based
      on increased electrophysiological heterogeneity of the myocardium. We developed a
      multi-site monophasic action potential recording system for an isolated rabbit
      heart to study the effects of global ischaemia on the electrophysiological
      properties at different ventricular sites simultaneously. The hearts were paced
      from the right ventricle (RV), and conduction time (CT), action potential
      duration (APD) and total repolarization time (TRT = [CT + APD]) were measured
      during normal perfusion and ischaemia. The dispersion of these parameters was
      calculated as the maximal difference between simultaneous recordings.
      Inducibility of VTA by programmed extrastimulation (ES) was investigated under
      normal and ischaemic conditions. During global ischaemia, CT increased
      progressively, showing a faster and greater increase at the left ventricle (LV)
      than at the RV. After 10 min the prolongation of CT reached a plateau at the LV
      while it continued to rise in the RV. The dispersion of CT increased from 14.5 +/
      2.7 ms during normal perfusion to a maximum of 79.8 +/- 17.2 ms after 14 min of
      ischaemia (P < 0.0001). APD was uniform at the three sites (190.9 +/- 10.2, 185.0
      +/- 8.6 and 179.3 +/- 9.8 ms, ns) during normal perfusion but changed non
      uniformly during ischaemia. There was a transient lengthening of APD until 1 and
      3 min of ischaemia at the LV sites followed by a rapid shortening of APD. At the
      RV site, APD continued to increase until 5 min of ischaemia and then shortened
      gradually. Consequently, dispersion of APD showed a rapid initial rise from 17.7
      +/- 2.7 ms to 77.8 +/- 10.2 ms (P < 0.0001) followed by a slower final increase.
      TRT was uniform during normal perfusion (210.4 +/- 10.3, 213.1 +/- 7.8, 212.1 +/-
      10.3 ms, ns) but became non-uniform during global ischaemia. The dispersion of
      TRT increased from 15.4 +/- 4.2 ms to 92.6 +/- 23.2 ms (P < 0.0001) during 14 min
      of global ischaemia. Both CT and APD contributed independently to TRT and could
      either augment or partially compensate for the ischaemic alterations of the other
      parameter. ES induced VTA only during ischaemia (3.7 +/- 1.1 VTA per heart, P <
      0.0001) at coupling intervals between 220 and 380 ms. The dispersion of TRT of
      the last regular beat preceding VTA was 67.7 +/- 17.4 ms (P < 0.001). ES which
      triggered VTA showed a more than two-fold increase of CT dispersion compared to
      the last steady state beat (122.7 +/- 29.4%, P = 0.0001).(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8299642
TI  - Heart transplantation for terminal congestive heart failure in an acromegalic
      patient.
AB  - Dilated hypokinetic cardiomyopathy in an acromegalic patient is an uncommon
      event. Specific hormonal therapy with octreotide (a somatostatin analogue) is now
      recognized as able to improve cardiac failure. A case of worsening of cardiac
      function under such a therapy is described in this report. Octreotide was finally
      discontinued and a cardiac transplantation performed. Soon after surgery,
      treatment with octreotide was started again and no other adverse reaction was
      noticed. Furthermore, no deleterious or synergistic interaction between the
      somatostatin analogue and cyclosporine A was detected. A pharmacological
      hypothesis is given to explain the inability of octreotide to counteract cardiac
      failure. The patient died 6 months after surgery probably because of an acute
      episode of arrhythmia.

PMID- 8299643
TI  - Malignant epithelial mesothelioma presenting as cardiac tamponade.

PMID- 8299644
TI  - Late cardiac tamponade after self-injury with a needle.

PMID- 8299645
TI  - Myocardial infarction after chronic ergotamine abuse.
AB  - As a result of chronic ergotamine abuse, reversible arterial narrowing has been
      documented angiographically in peripheral, but not in coronary arteries. We
      report on a patient with no cardiovascular risk factors, but because of chronic
      ergotamine abuse suffered on acute myocardial infarction, complicated by
      ventricular fibrillation. Coronary angiography performed 3 days after
      resuscitation revealed a distal occlusion of the left anterior descending artery.
      Three months later, spontaneous recanalization had occurred, and no residual
      narrowing was seen angiographically. Thus, surveillance of patients with migraine
      headache to avoid chronic ergotamine abuse is recommended to prevent
      cardiovascular complications.

PMID- 8299646
TI  - Utilization of coronary angioplasty and cost of angioplasty disposables in 14
      Western European countries.

PMID- 8299647
TI  - Antibody-guided scintigraphy: targeting of the "magic bullet".

PMID- 8299648
TI  - Polyclonal 111In-IgG, 125I-LDL and 125I-endothelin-1 accumulation in experimental
      arterial wall injury.
AB  - To test iodine-125 labelled low-density lipoprotein (125I-LDL), polyclonal indium
      111 labelled immunoglobulin G (111In-IgG) and iodine-125 labelled endothelin-1
      uptake in metabolically active atheromatous plaques after arterial wall injury,
      we performed balloon de-endothelialization of carotid arteries or abdominal
      aortas in 24 New Zealand male rabbits which were fed with a normal diet (n = 14)
      or a hypercholesterolaemic diet (n = 10) after surgery. Six weeks later the
      animals were injected with 200 microCi of 125I-LDL and/or with 100 microCi of
      111In-IgG or with 9 microCi of 125I-endothelin-1. Forty-eight hours later the
      animals were sacrificed. Carotid arteries and aortas were removed, counted and
      fixed for autoradiography and light microscopy examination. Contralateral carotid
      arteries and thoracic aortas served as controls. Significant 111In-IgG uptake was
      observed in the injured arteries at autoradiography, with localization mainly in
      the healing edges, and at well counting. The percentage of the injected dose per
      gram (%D.inj/g) was 0.0188 +/- 0.06 versus 0.0059 +/- 0.003 in controls (P <
      0.05). There was no difference in 111In-IgG uptake between arteries with injury
      alone and those with active atheroma formation at the site of the injury.
      Significant 125I-LDL uptake was observed only when lipid deposition was present
      at light microscopy (%D.inj/g of 0.0024 +/- 0.0005 vs. 0.0010 +/- 0.0003 in
      controls, P < 0.05). 125I-endothelin-1 accumulation was observed in four of five
      injured aortas both at autoradiography, with diffuse localization, and at well
      counting (%D.inj/g of 0.0012 +/- 0.0004 in the abdominal aortas vs 0.0008 +/-
      0.0003 in the thoracic aortas).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299649
TI  - Localization of IBF as a D-2 dopamine receptor imaging agent in nonhuman
      primates.
AB  - Preliminary study of iodine-123 labeled IBF, (S)-5-iodo-7-N-[(1-ethyl-2
      pyrrolidinyl)methyl] carboxamido-2, 3-dihydrobenzofuran, has demonstrated the
      potential of using this agent to evaluate the status of the CNS D-2 dopamine
      receptor in humans. To further characterize this ligand and evaluate single
      photon emission tomography (SPET) quantitation, a detailed biodistribution study
      in monkeys (Macaca fascicularis) with 123I- and 125I-IBF was performed. The dual
      tracer was simultaneously injected for in vivo imaging, bio-distribution, and ex
      vivo autoradiography in the same monkey. After the injection, SPET data (10
      min/frame x 15) were collected with a triple-head gamma camera. Dynamic imaging
      data indicated that IBF localized in basal ganglia (BG) with a half life of 90
      120 min. Other regions, i.e., cerebellum (CB) and cortex (CX), showed very low
      uptake. At 2.2 h after the injection, the monkey was sacrificed. Organ
      distribution data indicated that, as expected, there was a significant uptake in
      basal ganglia (0.029% ID/g), and the BG/CB and BG/CX ratios were 17.8 and 14.2
      respectively. Lower ratios were obtained from SPET image analysis (BG/CB = 3.5 at
      2.5 h). The eye uptake was observed with SPET, but was only quantified on
      autoradiograms with significant uptake (0.017% ID/g). Autoradiography of the eye
      demonstrated that predominant uptake was localized in the ciliary body and the
      choroid. The selective retention and high BG/CB ratio of 123I-IBF make it a
      useful agent for in vivo D-2 dopamine receptor imaging with SPET.

PMID- 8299650
TI  - A comparison of iodine-123 meta-iodobenzylguanidine scintigraphy and single bone
      marrow aspiration biopsy in the diagnosis and follow-up of 26 children with
      neuroblastoma.
AB  - In staging neuroblastomas, the demonstration of tumoural invasion of the bone
      marrow is an important criterion with regard to the therapeutic prospects and the
      prognosis. Iliac crest aspiration sampling has been used routinely for the
      detection of bone marrow metastases in neuroblastoma. However, due to the limited
      character of the sampling, it sometimes leads to false-negative results. Another
      procedure which is used to determine the extent of neuroblastoma is
      metaiodobenzylguanidine (mIBG) scintigraphy. In order to establish the respective
      merits of both diagnostic techniques retrospectively, 148 iodine-123 mIBG scans
      of 26 children with neuroblastoma have been re-evaluated and compared with the
      results of routine bone marrow samples obtained within a 4-week period before or
      after scanning. Three types of mIBG uptake in the bone/bone marrow could be
      differentiated: (1) no visualization of the skeleton; (2) diffuse uptake in the
      skeleton with or without focally increased uptake, which indicates massive,
      diffuse bone marrow invasion by the tumour; and (3) focal tracer accumulation in
      one or several bones. No tracer uptake was observed in the skeleton in 91 scans.
      In 89 of the 91 the bone marrow biopsy was negative. Twenty-four scans showed
      diffuse skeletal uptake with or without foci. The bone marrow biopsies were
      negative for eight of those 24 scans. Hyperactive foci in one or more bones
      without diffuse tracer accumulation in the skeleton were detected in 33 scans. In
      only 7 of these 33 scans did bone marrow biopsy specimens from the iliac MDP
      crest contain neuroblastoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299651
TI  - Iodine-131 metaiodobenzylguanidine scintigraphy for localization of lesions in
      children with neuroblastoma: comparison with computed tomography and
      ultrasonography.
AB  - Iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy, computed tomography (CT)
      and ultrasonography (US) were used to localize tumour lesions in 28 children with
      histologically proven neuroblastoma. Overall, a total of 73 lesions were detected
      on imaging studies. MIBG scintigraphy, CT and US localized 63 (86%), 49 (67%) and
      36 (49%) of these lesions, respectively. The findings of the three imaging
      techniques were concordant in respect of only 31 (42%) of the lesions. The best
      agreement among MIBG scintigraphy, CT and US was observed for abdominal lesions
      (the techniques were concordant for 22 of 23 lesions, i.e. 96%). MIBG
      scintigraphy detected nine out of ten (90%) liver metastases, but agreement with
      CT and US was observed in only six instances (60%). The imaging findings were
      concordant in respect of only two (33%) out of six lymph node metastases; the
      MIBG scan was normal in the other four cases. Imaging agreement was observed for
      a lesion located in the pelvis. MIBG and CT findings were concordant in four
      lesions located in the chest, but US was not performed. MIBG scintigraphy
      depicted the majority (96%) of the skeletal lesions (23/24); CT showed five of
      these, but, again, US was not performed. The imaging findings were not concordant
      as regards the remaining five lesions located in different anatomical sites. The
      results indicated that MIBG imaging is more sensitive that CT and US in
      localizing the majority of neuroblastoma lesions. Since the metastatic spread of
      neuroblastoma is unpredictable, we recommend MIBG scintigraphy as the initial
      imaging modality for staging of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299652
TI  - Usefulness of technetium-99m hydroxymethylene diphosphonate scans in localizing
      bone metastases of differentiated thyroid carcinoma.
AB  - Iodine-131 is uniquely able to demonstrate iodine uptake of differentiated
      thyroid carcinoma (DTC), but precise localization may be difficult, especially in
      the thorax, due to the quality of image resolution with 131I and the lack of
      anatomical landmarks. When bone metastases do not show radioiodine uptake bone
      scintigraphy can be used to detect them. We studied two groups of patients. In
      group 1, 15 patients with known bone metastases of DTC were treated with 3.7 GBq
      131I. After 4 or 5 days, technetium-99m hydroxymethylene diphosphonate (HMDP; 740
      MBq) was injected and a whole-body scan with simultaneous acquisition of 131I and
      99mTc-HMDP images was carried out using a large field of view gamma camera fitted
      with a high-energy collimator. Technetium uptake was abnormal in 47 of 63
      localizations, being increased in 29 foci, decreased in 7 and heterogeneous in
      11. The superimposition of 131I and 99mTc-HMDP scans permitted an accurate
      localization in 80% of spine metastases and in 46% of osseous thoracic
      localizations, even in the presence of lung metastases. In group 2, 9 patients,
      who had bone pain, neurological signs or elevated serum thyroglobulin, had DTC
      bone metastases without iodine uptake. They received a diagnostic dose of 99mTc
      HMDP 3h prior to scintigraphy with a large field of view gamma camera fitted with
      a low-energy collimator. Technetium uptake was abnormal in 37 of 38
      localizations, being increased in 34 foci and decreased in 3. One false-negative
      was found in a skull metastasis. In both groups of patients, 99mTc-HMDP scans
      were useful.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299653
TI  - Factor analysis as a means of determining response to chemotherapy in patients
      with osteogenic sarcoma.
AB  - The prognosis of localized osteogenic sarcoma (OS) has improved considerably
      since the introduction of neoadjuvant chemotherapy. However, there is a subset of
      patients who do not show full benefit from neoadjuvant chemotherapy because of
      chemoresistance. The early identification of poor responders to chemotherapy
      during neoadjuvant therapy remains difficult. In order to evaluate the role of
      bone scintigraphy we report our experience of dynamic technetium-99m
      hydroxymethylene diphosphonate bone scintigraphy in 19 cases of paediatric
      osteogenic sarcomas. Before the beginning of chemotherapy, a dynamic scan was
      recorded during 30 min followed by static images at 3 h. The procedure was
      repeated halfway through the course of chemotherapy (6th week). Histological
      grading of the response to chemotherapy was carried out in the 12th week, showing
      nine good responses and ten poor responses. Factor analysis of dynamic structures
      (FADS) applied to dynamic scans allowed us to identify three factors termed
      vascular, "soft tissue" and osseous factors. The effect of chemotherapy on each
      factor was evaluated. Using FADS we were able to detect all the poor histological
      responders with the combination of vascular and osseous factors. Six out of nine
      good histological responders were also classified as scintigraphic responders.
      FADS applied to dynamic bone scans allowed us to identify at an early stage all
      the poor histological responders to neoadjuvant chemotherapy. This method may
      have clinical relevance for the therapeutic strategy in patients with OS.

PMID- 8299654
TI  - Resting technetium-99m methoxyisobutylisonitrile cardiac imaging in chronic
      coronary artery disease: comparison with rest-redistribution thallium-201
      scintigraphy.
AB  - We studied 19 patients with angiographically proven coronary artery disease and
      left ventricular dysfunction (ejection fraction 33% +/- 8%) by resting technetium
      99m methoxyisobutylisonitrile (99mTc-MIBI) and rest-redistribution thallium-201
      cardiac imaging. Thallium and 99mTc-MIBI studies were visually analysed. Of 285
      segments, 203 (71%) had normal thallium uptake, 48 (17%) showed reversible
      thallium defects and 34 (12%) showed irreversible thallium defects. Of these 34
      irreversible thallium defects, 19 (56%) were moderate and 15 (44%) were severe.
      Of the corresponding 285 segments, 200 (70%) had normal 99mTc-MIBI uptake, while
      37 (13%) showed moderate and 48 (17%) showed severe reduction of 99mTc-MIBI
      uptake. Myocardial segmental agreement for regional uptake score between initial
      thallium and resting 99mTc-MIBI images was 90% (kappa = 0.78). Segmental
      agreement between delayed thallium and resting 99mTc-MIBI images was 77% (kappa =
      0.44). In particular, in 26 (9%) segments 99mTc-MIBI uptake was severely reduced
      while delayed thallium uptake was normal or only moderately reduced. These data
      suggest that although rest-redistribution thallium and resting 99mTc-MIBI cardiac
      imaging provide concordant results in the majority of myocardial segments, some
      segments with severely reduced resting 99mTc-MIBI uptake may contain viable but
      hypoperfused myocardium. Thus, conclusions on myocardial viability based on 99mTc
      MIBI uptake should be made with caution in chronic coronary artery disease.

PMID- 8299655
TI  - A new quantitative method for the analysis of cardiac perfusion tomography
      (SPET): validation in post-infarct patients treated with thrombolytic therapy.
AB  - In this study a new method for assessment of perfusion defects (PDs) derived from
      myocardial perfusion tomograms was evaluated in patients treated with
      thrombolytic therapy. Using global constraints and dynamic programming, a model
      based delineation algorithm defined myocardial borders, the basal plane and
      absolute and relative PD size in 49 thallium-201 chloride (201TL CL) and 60
      technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) tomograms. Tomographic
      (single-photon emission tomography: SPET) and planar quantification of PDs was
      compared to enzymatic infarct size as well as to global (LVEF) and regional
      ventricular function (RWM) obtained by contrast angiography. The algorithm
      delineated the myocardium and the valve plane in most cases, even when large PDs
      were present. Manual correction of the automatic delineation of the basal plane
      was necessary in less than 20% of the studies. Using 201Tl Cl, LVEF correlated
      better with tomographic PD (r = -0.67) than with planar PD (r = -0.54). Comparing
      planar to tomographic imaging using 99mTc-MIBI, a higher correlation with
      enzymatic infarct size (r = 0.73 vs 0.57) and with global ventricular function (r
      = 0.64 vs -0.52) was found when tomographic techniques were used. No close
      correlation between PD and RWM was found. The beneficial effect of thrombolysis
      was shown by a significant difference of PD in patients with open versus occluded
      infarct-related vessels. It can be concluded that this new automated algorithm
      for quantification of SPET perfusion defect size provides a useful tool in
      evaluating thrombolytic therapy.

PMID- 8299657
TI  - Early response monitoring in malignant lymphoma using fluorine-18
      fluorodeoxyglucose single-photon emission tomography.
AB  - Metabolic response monitoring early during chemotherapy may have a major impact
      on clinical management of patients with malignant lymphoma. In two patients with
      non-Hodgkin's lymphoma fluorine-18 fluorodeoxyglucose (18FDG) single-photon
      emission tomography (SPET) studies were performed during the first two
      chemotherapeutic cycles. Persisting uptake predicted treatment failure whereas a
      sharp reduction of 18FDG uptake was demonstrated in the case of a responsive
      tumour. Qualitative analysis of conventional 18FDG imaging may thus serve to
      identify patients with a non-responding tumour. The potential of this technique
      in the determination of the initial response remains to be established. Imaging
      with 18FDG and SPET appears promising as a more easily available methodology than
      18FDG positron emission tomography.

PMID- 8299656
TI  - Aerosols for therapy and diagnosis.
AB  - Aerosols are defined as any mixture of solid or liquid particles/droplets that
      are stable as a suspension in air. Aerosols influence the lives of a large
      majority of the population. A proportion of particulates exacerbate or induce
      lung disease. Other aerosols are used in the prevention or control of lung
      disease or in the investigation of disease. This review covers the mechanisms of
      deposition of aerosols, the production and sizing of aerosols, factors affecting
      the variability in output from nebulisers and the use of radionuclides in
      defining drug deposition from therapeutic nebulisers.

PMID- 8299658
TI  - European Association of Clinical Pharmacology and Therapeutics.

PMID- 8299659
TI  - Carbamazepine and its metabolites in neuralgias: concentration-effect relations.
AB  - The aim of this study was to investigate the use of carbamazepine in the
      treatment of neuralgic pain and to determine a therapeutic plasma concentration
      range for carbamazepine in neuralgias. The relation between plasma concentration
      and the response to treatment (reduction in pain) was examined by logistic
      regression analysis of carbamazepine and its metabolites, the epoxide, the diol,
      and 2-hydroxycarbamazepine. The plasma concentrations of carbamazepine, the
      epoxide, and the diol were significantly related to the probability of a 25%
      reduction in pain. Only carbamazepine was significantly related to the
      probability of 50% and 75% pain reduction. However, multiple regression analysis
      with backward elimination of the data showed a significant correlation between
      both carbamazepine and the epoxide with regard to the probability of 50% and 75%
      reductions in pain. This confirms the previous finding that the epoxide has
      antineuralgic properties [Tomson and Bertilsson 1984]. The therapeutic plasma
      concentration range for carbamazepine in neuralgias, defined as the range of
      concentrations that would be expected to provide a 25-75% reduction in pain in
      50% of patients, was 2-7 micrograms.ml-1 (HPLC) or 5-17 micrograms.ml-1 (EMIT).

PMID- 8299660
TI  - Tremor in healthy volunteers after bambuterol and terbutaline CR-tablets.
AB  - Bambuterol tablets, 10 and 20 mg, and terbutaline CR-tablets, 5 and 7.5 mg, have
      been compared for their capacity to produce subjectively determined tremor in a
      randomised, double-blind, cross-over study in 40 healthy volunteers. The duration
      of each treatment was one week, with an intervening washout period of at least 2
      weeks. On the second and the last treatment days in each period, tremor was
      subjectively assessed on six occasions. In addition, an overall assessment of
      night and day tremor was made each morning and evening. Analyses were made for
      the second and last treatment days and during the treatment week. Paired
      comparisons for tremor during daytime showed a significant difference between the
      treatments, with the exception of bambuterol 20 mg and terbutaline 5 mg.
      Bambuterol 10 mg caused less tremor and terbutaline 7.5 mg caused more tremor
      than the other treatments. At the end of the week, the differences were smaller
      and were only significant when comparing bambuterol 10 mg with the 20 mg dose and
      with high dose terbutaline. Terbutaline 7.5 mg caused more tremor at night than
      the other treatments. The tremor experienced was generally mild, and after
      bambuterol 10 mg it was almost negligible (mean 0.13 after the first dose). Two
      subjects recorded a score of 3 after terbutaline 7.5 mg. The results indicate
      that, in doses equipotent with regard to bronchodilation, tremor is less
      pronounced after bambuterol as compared to controlled release tablets of
      terbutaline.

PMID- 8299661
TI  - Effects of amlodipine on renal haemodynamics in mild to moderate hypertensive
      patients. A randomized controlled study versus placebo.
AB  - In this study the efficacy and safety of short-term amlodipine administration on
      renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our
      final goal was to evaluate whether the reduced blood pressure induced by
      treatment was associated with maintenance of renal function. After a run-in
      period with placebo, 30 hypertensive patients without cardiac or renal diseases
      were randomly allocated to a double-blind 4 weeks controlled study with
      amlodipine 10 mg once a day (15 patients) or placebo (15 patients). Renal
      haemodynamic measurements included effective renal plasma flow (ERPF) and
      glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and
      99mTc, with methods described by Schlegel and Gates, respectively. In addition,
      effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF =
      GFR/ERPF) and renal vascular resistance (RVR = MBP x 80/ERBF) were calculated.
      Plasma renin activity (PRA), serum aldosterone (ALD) and urinary excretion of
      sodium (NaU) were evaluated. At the end of amlodipine administration a
      significant decrease (P < 0.001) in SBP, DBP and MBP from baseline values was
      observed. A significant decrease (P < 0.01) in RVR and significant increases (P <
      0.05) in ERPF, ERBF and in NaU were also found, without relevant changes in GFR,
      FF, PRA and ALD. No significant variation in clinical and renal measurements was
      observed in the placebo group. No relevant side effects were observed in either
      group. In conclusion, amlodipine was effective in lowering blood pressure in mild
      to moderate hypertension and exerted favourable effects on renal haemodynamics
      and function.

PMID- 8299662
TI  - The effects of single doses of CL284,846, lorazepam, and placebo on psychomotor
      and memory function in normal male volunteers.
AB  - The effects of single doses of CL284,846 (20 mg), lorazepam (2 mg) and placebo on
      psychomotor performance, memory function and subjective feelings were assessed in
      12 normal, healthy male volunteers. Each subject received each treatment in
      balanced order and a minimum of 6 days was left between treatments. The subjects
      performance on a comprehensive battery of tests of psychomotor performance,
      memory function and subjective ratings was assessed pre-treatment and at 1, 3 and
      5 h post-treatment. In general, the effects of CL284,846 on memory were similar
      to those of lorazepam at 1 h post-treatment but, recovery was rapid with
      CL284,846. Impairments induced by lorazepam persisted throughout the post-drug
      testing sessions. This pattern of effects was repeated across most of the
      variables tested. However, at 1 h, CL284,846 produced less marked psychomotor
      impairment than lorazepam. The results of this study suggest that CL284,846 is a
      safe, rapid acting and effective sedative with some clear advantages over
      lorazepam with respect to unwanted cognitive and psychomotor impairments.

PMID- 8299663
TI  - Renal effects of manidipine hydrochloride. A new calcium antagonist in
      hypertensive patients.
AB  - The renal effects of manidipine hydrochloride were investigated in ten
      hospitalised patients with mild-to-moderate essential hypertension. After a one
      week placebo period, manidipine was given for 1 week in a dose rising from 5 mg
      to 10 mg or 20 mg daily to normalise the mean blood pressure measured after 2 h.
      Blood pressure had decreased from 171/101 to 147/86 mm Hg at the end of
      manidipine treatment. The pulse rate was unaltered. Renal vascular resistance
      decreased from 1.90 to 1.33 dyn.s.cm-5/1.48 m2 x 10(4), and renal blood flow and
      glomerular filtration rate increased from 522 to 662 ml.min-1 x 1.48 m-2 and from
      81 to 93 ml.min-1 x 1.48 m-2, respectively, in spite of a fall in renal perfusion
      pressure. Manidipine reduced the filtration fraction from 0.260 to 0.243,
      suggesting a preferential reduction in efferent arteriolar resistance. The
      fractional excretion of sodium and potassium did not change. Manidipine did not
      produce any significant alteration in plasma renin activity or in the plasma
      aldosterone concentration. The results indicate that manidipine has favourable
      renal effects and a concomitant hypotensive action in patients with mild-to
      moderate essential hypertension.

PMID- 8299664
TI  - The acute haemodynamic and renal effects of oral felodipine and ramipril in
      healthy subjects.
AB  - The aim of the present investigation was to compare the acute haemodynamic and
      renal effects of the calcium antagonist felodipine with the ACE inhibitor
      ramipril and with placebo. Single oral doses of felodipine 5 and 20 mg, ramipril
      2.5 and 10 mg, and placebo were given to ten healthy subjects in a double-blind
      cross-over study. Blood pressure, heart rate, forearm blood flow (FBF), forearm
      vascular resistance (FVR), renal blood flow (RBF), renal vascular resistance
      (RVR), glomerular filtration rate (GFR), filtration fraction (FF), diuresis, and
      sodium excretion were recorded for 4.75 h after administration. Felodipine 20 mg
      caused a significant fall in diastolic blood pressure, maximal 12% compared with
      placebo, while there were no significant effects of felodipine 5 mg or the two
      doses of ramipril. Heart rate increased significantly after both doses of
      felodipine, maximal 28% after the 20 mg dose. There was also a small but
      significant increase in heart rate of 12% after ramipril 2.5 mg. FVR fell
      significantly after both doses of felodipine, maximal 38% after the 20 mg dose.
      There were no significant changes in FVR after any of the ramipril doses. Both
      doses of felodipine and both doses of ramipril caused significant reductions in
      RVR. Maximal reduction, 33%, was found after felodipine 20 mg. There were no
      significant changes in GFR or FF with either drug. Felodipine caused a
      significant increase in natriuresis, maximal 129% while ramipril did not.

PMID- 8299665
TI  - Effect of garlic on platelet aggregation in patients with increased risk of
      juvenile ischaemic attack.
AB  - A platelet-inhibiting effect is described for garlic. In this double-blind,
      placebo-controlled study on 60 voluntary subjects with cerebrovascular risk
      factors and constantly increased platelet aggregation it was demonstrated that
      the daily ingestion of 800 mg of powdered garlic (in the form of coated tablets)
      over 4 weeks led to a significant inhibition of the pathologically increased
      ratio of circulating platelet aggregates and of spontaneous platelet aggregation.
      The ratio of circulating platelet aggregates decreased by 10.3%, from 1.17 +/-
      0.08 to 1.05 +/- 0.11 (P < 0.01), and spontaneous platelet aggregation by 56.3%,
      from 40.7 +/- 23.3 to 17.8 +/- 23.2 degrees (P < 0.01) during the garlic phase.
      There were no significant changes in the placebo group. The parallel group
      comparison (garlic versus placebo) revealed a significantly different ratio of
      circulating platelet aggregates after 4 weeks of treatment (P < 0.05). After the
      4-week wash-out phase the values increased again to 1.19 +/- 0.32 and 34.9 +/-
      28.7 degrees, reaching the initial values (run-in phase prior to the ingestion of
      garlic). Since garlic is well tolerated it would be worth testing it in a
      controlled clinical trial for usefulness in preventing disease manifestations
      associated with platelet aggregation.

PMID- 8299666
TI  - Minoxidil sulphation in human liver and platelets. A study of interindividual
      variability.
AB  - Minoxidil requires to be sulphated to exert its hypotensive effect. We report on
      interindividual variability in the rate of minoxidil sulphation in 118 specimens
      of human liver and in platelets obtained from 100 healthy subjects and 100
      newborns. The frequency distribution histogram of the hepatic activity of
      minoxidil sulphotransferase was positively skewed; the mean was 631 pmol.min-1 x
      mg-1. After logarithmic transformation of the enzyme activity, the frequency
      distribution histogram became symmetrical and did not significantly deviate from
      normality. The rate of minoxidil sulphation was not different in platelets from
      adults (0.74 pmol.min-1 x mg-1) and newborns (1.16 pmol.min-1 x mg-1). The
      frequency distribution histograms were positively skewed and the results of
      normal equivalent deviation analysis was compatible with the presence of at least
      two subgroups of sulphotransferase in liver and platelets. Thus, two phenotypes
      of sulphotransferase exist in human liver and platelets, and the "extensive
      sulphator" phenotype contributes to skewing the frequency distribution. In
      platelets, the percentage of subjects that fall in the two subgroups is different
      at birth and in adulthood. This can explain the different shape of the frequency
      distribution in newborn and adult platelets and suggests that platelet minoxidil
      sulphotransferase undergoes modification after birth.

PMID- 8299667
TI  - Positive correlation between probucol in low density lipoprotein and LDL
      lowering.
AB  - The relationship between the content of probucol in plasma and lipid lowering was
      studied after administration of probucol. The study group consisted of 44
      patients with Type II hyperlipidaemia (mean age 56 y). Total cholesterol level
      was decreased from 293 to 232 mg.dl-1 by the administration of probucol. The
      plasma probucol concentration was 2.03 mg.dl-1 after 4 weeks of administration of
      500 mg b.d. Although there was no relationship between the change in total
      cholesterol and the plasma probucol, a linear relation was observed between the
      decrease in LDL-cholesterol concentration and the probucol concentration in LDL.
      Neither the VLDL nor the HDL-probucol content were related to the magnitude of
      the decrease in lipoprotein cholesterol. The present study has demonstrated that
      an increase in the probucol content in LDL was associated with a decrease in
      plasma LDL-cholesterol.

PMID- 8299668
TI  - Locally deposited but not inhaled frusemide reduces nasal potential difference in
      healthy subjects.
AB  - Previous publications suggest that prolonged inhalation of frusemide (F) does not
      cause a fall in the nasal transepithelial potential difference (PD) whereas
      locally deposited F does. In an attempt to reconcile these observations, we have
      measured the effect of inhalation through the nose and local deposition of F,
      amiloride (A), bumetanide (B) and salbutamol (S) on nasal PD in 7 healthy male
      volunteers in a randomised, double blind study. Solutions of drugs ranging from
      10(-6) M to 10(-3) M (3 x 10(-8) M to 3 x 10(-5) M for B) in phosphate buffered
      saline 0.5 ml (PBS) were sequentially deposited in both nostrils, and nasal PD
      was measured 5 min after each dose. In 10 further volunteers, 10(-2) M solutions
      of A, F and S (3 x 10(-4) M for B) 5 ml were nebulised through the nose for 15
      min, when nasal PD was measured. Resting PD was similar in the left and right
      nostrils averaging -17.1 mV (lumen negative). Placebo, inhaled of deposited B and
      S, and inhaled F did not change nasal PD. Topically deposited F significantly
      lowered PDmax in a dose-dependent manner [10(-4) M, -12% from baseline; 10(-3) M,
      -24%] as did the more potent A [10(-5) M, -19%; 10(-4) M, -31%; 10(-3) M, -47%].
      Nebulised A (10(-2) M) had the same effect on nasal PD as deposited A (10(-4) M).
      The effects of locally deposited F and A (10(-3) M) on nasal PD were
      additive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299669
TI  - Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy
      volunteers.
AB  - Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and
      opiate withdrawal syndromes. Its absorption and disposition kinetics have been
      studied in 8 healthy male volunteers following oral administration of single
      doses of 12.5, 25 and 50 mg kg-1. The AUC increased disproportionately with the
      dose and so the apparent oral clearance decreased significantly as the dose was
      increased, whereas the terminal half-life and mean residence time increased. The
      peak plasma concentrations normalised to the lowest dose fell significantly with
      increasing doses, whilst the corresponding peak times increased. These findings
      suggest that both the oral absorption and the elimination of GHB are capacity
      limited processes. GHB did not bind to significant extent to plasma proteins over
      the therapeutic concentration range. The pharmacokinetic parameters in healthy
      volunteers were not significantly different from those previously observed in
      alcohol-dependent patients with compensated alcoholic liver disease.

PMID- 8299670
TI  - Modelling circadian variation in the pharmacokinetics of non-steroidal anti
      inflammatory drugs.
AB  - A one-compartment model with first-order absorption has provided good fits to
      five sets of indomethacin data and four sets of ketoprofen data taken at
      different times of day. There was substantial variation in the model parameters
      with time of administration and most of the features of this variation applied
      equally to both drugs. From the data examined, the source of variation appears to
      be mainly in the absorption phase and this was confirmed using a chronokinetic
      analysis, in which simultaneous fits were obtained with time-variant rate
      parameters. However, there may also be circadian variation in protein binding.
      The danger of quoting parameter values for either of these two drugs based on
      administration at a single time of day has been illustrated, and this may well be
      true for other drugs.

PMID- 8299671
TI  - Investigation of nimodipine pharmacokinetics in Chinese patients with acute
      subarachnoid haemorrhage.
AB  - Nimodipine pharmacokinetics was investigated in 12 Chinese patients with acute
      subarachnoid haemorrhage receiving an IV infusion of 1.6 or 2 mg/h (based on
      estimated body weight) for 10 days. Peripheral venous blood samples were
      collected for up to 4 days and plasma nimodipine was assayed by GC/ECD. The mean
      value was taken as the steady state concentration (Css) and Clearance (CL)
      (hourly dose/Css) was calculated. Eight survivors were given oral nimodipine (60
      or 90 mg) every 6h (based on body weight), blood was sampled over 6 h and the
      plasma nimodipine level determined. The values for Css, CL and CL.kg-1 were 33.5
      micrograms.l-1, 58 l.h-1 and 1.0 l.h-1 x kg-1 respectively; in survivors
      receiving the drug orally, bioavailability of the 30 mg tablet was 9%. In one
      very sick patient given crushed tablets by naso-gastric tube, the AUC was very
      low; in vitro studies indicated that adsorption of nimodipine by the tubing was
      unlikely to have been the cause. The pharmacokinetic findings in Chinese patients
      are comparable to previously reported values in Caucasians.

PMID- 8299672
TI  - Pharmacokinetics of lansoprazole in patients with renal or liver disease of
      varying severity.
AB  - The pharmacokinetics of lansoprazole (L) after a single oral dose of 30 mg was
      determined in 18 healthy volunteers, 17 renal failure patients and 24 hepatic
      failure patients; 8 hepatitis and 16 with compensated (CC) or uncompensated (UCC)
      cirrhosis. In renal failure, the absorption of L was unchanged, its half-life
      being similar to that in healthy subjects; a small change seen in mild renal
      failure patients (creatinine clearance between 40 and 60 ml/min) was attributed
      to the age of the patients. Urinary elimination, essentially as metabolites of
      lansoprazole, was decreased, in relation to the degree of renal impairment. In
      hepatitis patients, the AUC and t1/2 of L were doubled, without any change in
      Cmax. In cirrhotics tmax was prolonged, the AUC was increased (P < 0.001) and
      there was prolongation of t1/2 (6.1 h in CC and 7.2 h in UCC compared to 1.4 h in
      healthy subjects). These changes resulted from a decrease in the clearance of L.
      There was also an increase in its sulphone metabolite (Cmax, Rm) and a decrease
      in the hydroxylated metabolite (Cmax, Rm) in relation to the degree of liver
      disease, and reflecting a decrease in hydroxylation and biliary elimination.
      Thus, renal failure had no effect on the pharmacokinetics of L, but severe
      hepatic failure caused marked changes. A repeated dosing study would be necessary
      to evaluate the repercussions of the possible accumulation in cirrhotic patients.

PMID- 8299673
TI  - Pharmacodynamics and pharmacokinetics of eptastigmine in elderly subjects.
AB  - Eptastigmine is a new cholinesterase inhibitor, which may be potentially useful
      for the symptomatic treatment of Alzheimer's disease. A preliminary evaluation of
      its pharmacodynamic and pharmacokinetic profiles in the elderly has now been made
      in 6 healthy subjects (63-84 years of age) given 30 mg eptastigmine as a single
      oral dose. Blood was collected prior to and 1, 2, 3, 4, 6, 8, and 12 h after
      eptastigmine administration for measurement of cholinesterase inhibition in
      plasma and red blood cells and the plasma drug concentrations. The maximum plasma
      cholinesterase inhibition was 17%, which was reached 2.7 h after treatment. In
      red cells the maximum inhibition of the enzyme was 29% after 3.8 h. The estimated
      half-time of cholinesterase recovery was 12.4 h in plasma and 13.6 h in red blood
      cells. The peak plasma concentration of eptastigmine of 0.86 ng.ml-1 was reached
      after 1.4 h. Following absorption the drug was rapidly distributed into tissues
      (t1/2 alpha = 0.44 h) and then eliminated with a half-life of 12.1 h. The drug
      was well tolerated in all but one subject, who showed bradycardia with
      hypertension and nausea for about 2 h after the dose. The results indicate that
      oral administration of eptastigmine to elderly subjects produces long lasting
      inhibition of cholinesterase activity in plasma and in red blood cells.

PMID- 8299674
TI  - Effects of a sauna on the pharmacokinetics and pharmacodynamics of midazolam and
      ephedrine in healthy young women.
AB  - The effect of a sauna on the pharmacokinetics and pharmacodynamics of single
      doses of ephedrine 50 mg and midazolam 15 mg have been studied in 6 young healthy
      women in a placebo-controlled, double-blind study. The sauna (3 x 10 min;
      temperature 80-100 degrees C; relative humidity 30-50%) modified the
      pharmacokinetics of both drugs: it retarded the absorption of midazolam estimated
      as Ka values, and it reduced the mean plasma midazolam concentrations at 2 h;
      ephedrine, was absorbed more rapidly and the maximum plasma concentration
      occurred earlier than in the control sessions. Changes in the pharmacodynamics
      due to the sauna were consistent with the pharmacokinetic findings: midazolam
      decreased flicker recognition and induced exophoria significantly less during the
      early sauna period than in the control session, whereas ephedrine made the
      volunteers subjectively more alert at that time. Later, at 2.5 and 3.5 h (1 h 20
      min and 2 h 20 min after cessation of the sauna), and despite the equalisation of
      the plasma levels, midazolam caused significantly more exophoria after the sauna
      than in the control situation. This indicates an influence of a sauna on drug
      pharmacodynamics in the post-sauna adaptive phase. The results suggest that
      exposure to a sauna may alter both drug pharmacokinetics and pharmacodynamics.

PMID- 8299675
TI  - On the question of interindividual variations in chloroquine concentrations.
AB  - In a review of studies using appropriate methods for drug determinations and
      controlled intake, an interindividual variation in chloroquine concentrations of
      2.3 to 5.6-fold was found. In our department, steady-state concentrations were
      evaluated in 40 patients with rheumatic diseases. The variation in whole blood
      concentrations was 11-fold for chloroquine and 10-fold for the
      desethylchloroquine metabolite. The mean ratio between desethylchloroquine and
      chloroquine concentrations was 0.53 and the Spearman-Rank correlation 0.92. The
      correlation between age and the ratio of chloroquine concentration/dose was 0.36
      (P < 0.05) and the corresponding correlation for body weight was -0.43 (P <
      0.05). Our data indicate that body weight and age are important independent
      factors for the disposition of chloroquine. However, when extensive 100-fold
      variations in concentrations are found between individuals we suggest that the
      reliability of the dose intake should be questioned.

PMID- 8299676
TI  - Effect of iron deficiency anaemia and its treatment on single dose phenytoin
      bioavailability.
AB  - Iron deficiency is a common nutritional deficiency, which leads to structural
      functional and enzymatic changes in the body that may affect the pharmacokinetics
      of drugs. The present study in 7 normal volunteers and 8 adult male patients with
      iron deficiency anaemia (IDA) was done to investigate the effect of iron
      deficiency and its treatment with total dose iron (TDI) on the bioavailability of
      a single dose of phenytoin. Phenytoin bioavailability was investigated before and
      3 and 28 days after TDI. The bioavailability parameters Cmax, tmax, AUC and 2 h
      phenytoin concentrations were not significantly different in anaemic patients as
      compared to normal volunteers before or after treatment, except for an increase
      in tmax 28 days after TDI treatment.

PMID- 8299677
TI  - Ivermectin levels in human breastmilk.
AB  - Ivermectin levels were measured in breastmilk and plasma of 4 healthy mothers
      after an oral 150 micrograms/kg dose. Mean +/- S.D. plasma and milk values were
      37.9 +/- 0.54 and 14.13 +/- 0.43 (ng/ml) respectively. Steady-state ivermectin
      levels in milk were low. Our results suggest that exclusion of lactating mothers
      from mass chemotherapy with ivermectin may be unnecessary.

PMID- 8299678
TI  - Tolerance induction as a multi-step process.
AB  - Tolerant T cells are characterized by their partial or full resistance to
      activation by antigen. We investigated whether tolerant T cells were still
      receptive to further tolerogenic signals. T cells expressing a transgenic T cell
      receptor (TCR) specific for the major histocompatibility complex (MHC) class I
      molecule Kb were deleted in mice carrying Kb but not in mice expressing the
      mutant Kb-molecule Kbm1 [TCR (H-2bm1 x k) mice]. These T cells were tolerant in
      vivo but could be activated in vitro by the Kb antigen. This in vitro reactivity
      was abolished after the tolerant T cells encountered Kb-positive cells that had
      been intravenously injected. Furthermore, in TCR (H-2bm1 x k) mice expressing Kb
      only on hepatocytes, no T lymphocytes bearing the transgenic TCR could be found
      in the periphery, indicating that the additional contact with Kb on hepatocytes
      led to deletion of the tolerant T cells. These findings demonstrate that
      tolerance induction can be a multi-step process.

PMID- 8299679
TI  - Prenylated proteins and lymphocyte proliferation: inhibition by d-limonene
      related monoterpenes.
AB  - The aim of the present study was to explore the role of post-translational
      isoprenoid modification of cellular proteins in the proliferation of human
      lymphocytes. We here report that treatment of phytohemagglutinin-stimulated
      peripheral blood mononuclear cells with monoterpenes including d-limonene,
      perillic acid and perillyl alcohol (0.5-5 mM) which selectively inhibit the
      isoprenylation of 21-26-kDa proteins resulted in a dose-dependent inhibition of
      DNA synthesis. Cell cycle analysis revealed that perillic acid arrested cells in
      G1 and prevented cells from entering S phase in a manner similar to that induced
      by the specific 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, compactin.
      However, unlike compactin, the perillic acid-induced effects on lymphocyte
      proliferation were not prevented by addition of mevalonate. We also examined the
      incorporation of [3H]mevalonate into proteins in resting and phytohemagglutinin
      stimulated lymphocytes during the first 30 h of culture. While in unstimulated
      lymphocytes radioactivity was predominantly incorporated into a cluster of 21-26
      kDa proteins, mitogenic stimulation was associated with a striking increase in
      [3H]mevalonate incorporation into a protein (approximately 68 kDa) with migration
      characteristics similar to that of nuclear lamin B. Treatment of
      phytohemagglutinin-stimulated lymphocytes with 5 mM d-limonene, 2.5 mM perillic
      acid or 1.25 mM perillyl alcohol strongly suppressed [3H]mevalonate-labeling of
      proteins to a degree that correlated with the level of DNA synthesis inhibition.
      These findings suggest that those mevalonate-derived products required for
      lymphocyte proliferation may include one or more isoprenylated proteins and that
      the isoprenylation of these proteins is required for cell cycle progression.

PMID- 8299680
TI  - Neuronal interferon-gamma immunoreactive molecule: bioactivities and
      purification.
AB  - An interferon (IFN)-gamma immunoreactive molecule, localized to small neurons in
      peripheral sensory ganglia (N-IFN-gamma), has been detected with two mouse
      monoclonal antibodies (DB1 and DB16) directed against different epitopes of rat
      IFN-gamma. To define N-IFN-gamma with regard to its protein characteristics and
      bioactivities, DB1 and DB16 were used to purify N-IFN-gamma from rat trigeminal
      ganglia in a two-step sequential antibody-affinity procedure. Sodium
      dodecylsulfate polyacrylamide gel electrophoresis (PAGE) and silver staining of
      purified N-IFN-gamma displayed three bands with an approximate molecular mass of
      66, 62 and 54 kDa. The N-IFN-gamma bioactivity was confined to the protein
      stained on gel when native material was run on PAGE. Biological effects of pure N
      IFN-gamma were examined and compared with those of lymphocyte-derived recombinant
      IFN-gamma. N-IFN-gamma had antiviral effects in vitro and induced major
      histocompatibility complex class I and II antigens on macrophages and in cells in
      skeletal muscle cell cultures. N-IFN-gamma also stimulated myoblast proliferation
      and affected cholinergic receptor distribution on myotubes similar to recombinant
      IFN-gamma. Both molecules potently stimulated Trypanosoma brucei brucei growth.
      These data suggest that, although N-IFN-gamma is a protein distinct from
      lymphocyte-derived IFN-gamma, the two molecules have enough structural
      similarities to allow for antibody recognition of at least two epitopes, and
      action on similar target structures on both parasite and mammalian cells.

PMID- 8299681
TI  - The phosphoprotein phosphatase calcineurin controls calcium-dependent apoptosis
      in B cell lines.
AB  - Group I Burkitt's lymphoma cell lines and the B104 lymphoma cell line which
      expresses a phenotype of immature B cells undergo apoptosis after cross-linking
      of their surface immunoglobulin (Ig) receptors or after exposure to a calcium
      ionophore, while protein kinase C (PKC)-activating phorbol esters prevent such
      apoptosis. We show here that blockade of the phosphoprotein phosphatase
      calcineurin or phosphatase 2B by cyclosporin A (CsA) also protects these B cell
      lines against Ca(2+)-dependent apoptosis but not against apoptosis triggered by
      the PKC inhibitor chelerythrine or by serum deprivation. Okadaic acid, an
      inhibitor of phosphatases 1, 2A and 2C was ineffective. Among a series of human
      cytokines tested, only interferon-alpha and tumor necrosis factor-alpha were
      shown to protect against Ca(2+)-dependent apoptosis when used alone or in
      combination with CsA. In contrast to phorbol esters which block the progression
      into the S/G2 phases of the cell cycle, CsA partially restored the proliferation
      of cells exposed to the calcium ionophore. Altogether these data provide indirect
      evidence for the control of B cell apoptosis by the serine/threonine
      phosphorylation status of yet undefined key cellular substrates.

PMID- 8299682
TI  - The ability of H-2Dd molecule to affect natural resistance to hemopoietic
      allografts is an intrinsic property shared by Ddm1 but not Ld.
AB  - F1 hybrid resistance (HR) to parental bone marrow grafts is mediated by natural
      killer (NK) cells, and thought to be controlled by the non-class I hemopoietic
      histocompatibility (Hh) genes linked to the major histocompatibility complex
      (MHC). However, as in the in vitro NK cytotoxicity against hemopoietic targets,
      expression of certain class I MHC molecules does affect HR, although mechanisms
      underlying such an effect are not understood. In this study, we examine the
      relevance of the "self/non-self" property of class I molecules and the molecular
      domains responsible for this function. H-2b/Hh-1b lymphoma cells were transfected
      with class I H-2Dd or Ld gene, and its effect on the Hh-1 phenotype was examined
      by testing the transfectant's ability to competitively inhibit the in vivo
      rejection of parental H-2b/Hh-1b bone marrow grafts by irradiated F1 hybrid
      hosts. Multiple independent clones of transfectants show that the genomic or cDNA
      of the Dd gene, but not of Ld, renders the Hh-1b-positive cells incapable of
      inhibiting HR in F1 mice, although both genes belong to the same region of the
      same haplotype. The same effect could be observed not only in H-2b/d F1 mice for
      which Dd and Ld are self, but also in H-2b/k F1 mice for which both Dd and Ld are
      non-self. Thus, this function of the Dd molecule is an intrinsic property, not
      necessarily related to its self/non-self characteristic relative to the effector
      cells. Furthermore, given the nature of the assay used in this study, the results
      favor a "target interference" model as the underlying mechanism of the Dd effect.
      To locate the relevant domain(s) of the Dd molecule, mutant Ddm1 gene was tested
      and found to have the same effect as the non-mutant Dd. Ddm1 is a hybrid molecule
      between Dd and Ld, sharing with Dd only the alpha 1 domain and a portion of the
      alpha 2 domain. The two N-terminal domains of Ddm1 differ from those of Dd by
      three amino acid substitutions, two of which affect the molecules' peptide
      binding properties.

PMID- 8299683
TI  - A peptide binding weakly to the major histocompatibility molecule augments T cell
      responses.
AB  - An I-A(d)-derived peptide PB1 was found to enhance the reactivity of I-A(d)
      restricted T cells. The augmentative effect was not due to the cross-reactivity
      of PB1 peptide with antigens. PB1 had no effect on T cells specific for I-A(b)
      and I-E(k), nor did PB1 increase the T cell responses to concanavalin A and
      staphylococcal enterotoxin B. The strict I-A(d) specificity suggests that PB1
      enhances the recognition of antigen-I-A(d) complex by T cell receptor. PB1 bound
      to I-A(d) weakly. The augmentative effect could be found on other I-A(d)-binding
      peptides in appropriate conditions; however, PB1 was distinct in its prominently
      augmentative effect on all the I-A(d)-restricted T cells analyzed. A similar
      enhancing activity was demonstrated on a synthetic transferrin receptor peptide
      with minimum affinity for I-A(d). The unusual enhancing activity of PB1 may thus
      be attributed to the low I-A(d) binding affinity. It was postulated that the
      binding of low-affinity PB1 would not only stabilize I-A(d) structure, but also
      enhance the binding of other peptides. This was supported by the increased
      binding of OVA 323-339 and cI 84-98 to I-A(d) in the presence of PB1. The
      inclusion of PB1 in the immunization mixture also enhanced T cell responses in
      vivo, suggesting the possibility of using low-affinity peptide to promote
      specific immunity.

PMID- 8299684
TI  - Human tonsil, blood and bone marrow in vivo-induced B cells capable of
      spontaneous and high-rate immunoglobulin secretion in vitro: differences in the
      requirements for factors and for adherent and bone marrow stromal cells, as well
      as distinctive adhesion molecule expression.
AB  - Human B cells capable of spontaneous IgG secretion are commonly found in
      circulation and in lymphoid tissues such as tonsil and bone marrow (BM). The
      present study compares the mechanisms that regulate tonsil, blood and BM B cells
      capable of spontaneous IgG secretion. The BM cell subset produced IgG during a
      markedly longer period of time (14 days) than did tonsil and blood cell subsets
      (2-3 days). Blood and BM, but not tonsil, B cell IgG secretion depended on the
      presence of adherent cells, as demonstrated by adherent cell depletion and re
      addition experiments. Stromal BM cells supported linear IgG secretion by non
      adherent BM cells for 2 weeks, but were unable to prolong the short-term IgG
      secretion by tonsil and blood cells. Different factors induced IgG secretion in
      each of the three B cell populations as optimal IgG secretion by tonsil, blood or
      BM cell subsets required either tumor necrosis factor-alpha, interleukin-6 or
      fibronectin + interleukin-6, respectively. Finally, these populations also showed
      differences in the expression of adhesion molecules; the tonsilar cell subset was
      PNA+/- CD44+ CD49d+ CD49e- Leu-8+/-, the blood cell subset was PNA- CD44+/-
      CD49d+ CD49e- Leu-8+ and the BM cell subset was PNA- CD44+/- CD49d+ CD49e- Leu-8
      . These results suggest that the mechanisms controlling the final differentiation
      and the expression of adhesion molecules in these B lymphocytes exhibit
      territorial specificity.

PMID- 8299685
TI  - 4-1BB T-cell antigen binds to mature B cells and macrophages, and costimulates
      anti-mu-primed splenic B cells.
AB  - 4-1BB is expressed on activated murine T cells and may function as an accessory
      signaling molecule during T-cell activation. To identify putative 4-1BB ligands,
      a fusion protein consisting of the extracellular domain of 4-1BB fused to human
      placental alkaline phosphatase (4-1BB-AP) was constructed. Alkaline phosphatase
      activity could then be used as an indicator of the relative amount of bound 4
      1BB. These studies indicated that 4-1BB-AP specifically bound to the surface of
      various mature B and macrophage cell lines. 4-1BB-AP bound at low levels to T
      cell lines (non-activated and anti-CD3-activated), pre-B-cell lines, and an
      immature macrophage cell line. 4-1BB-AP did not bind to a glial tumor cell line,
      HeLa cells, or COS cells. In addition, 4-1BB-AP bound at higher levels to F(ab')2
      anti-mu-activated primary B cells compared to anti-CD3-activated primary T cells.
      Scatchard analysis indicated that the A20 B cell lymphoma expressed 3680 binding
      sites per cell with a Kd of 1.86 nM. Affinity cross-linking studies demonstrated
      that a major cell surface species of 120 kDa bound to 4-1BB-AP; 4-1BB-AP also
      bound to a minor species of approximately 60 kDa. The addition of
      paraformaldehyde-fixed SF21 cells expressing recombinant 4-1BB synergized with
      F(ab')2 anti-mu in inducing splenic B cell proliferation suggesting that 4-1BB
      may function as a regulator of B cell growth.

PMID- 8299686
TI  - Identification of an HLA-DQ2 peptide binding motif and HLA-DPw3-bound self
      peptide by pool sequencing.
AB  - Molecules of the major histocompatibility complex (MHC) present antigenic
      peptides to T cells. Sequencing peptide pools eluted from MHC class I molecules
      has established allele-specific peptide binding motifs. We applied pool
      sequencing to analyze human MHC class II-bound peptides and found that HLA-DQ2
      eluted peptides predominantly contained lysine, isoleucine, and phenylalanine at
      relative position i, i + 3 and i + 8, respectively. These residues putatively
      represent anchor residues for MHC binding. Analysis of a heterogeneous HLA
      DPw3/DPw4-eluted peptide pool yielded a sequence matching an epitope from the
      endogenous enzyme glyceraldehyde-3-phosphate dehydrogenase. This self-peptide and
      a partially identical, known allo-epitope bound specifically to DPw3 and DR13
      molecules, suggesting the sharing of a binding motif. In particular, the presence
      of an arginine at relative position 4 appeared important for binding to these HLA
      class II specificities. Thus, pool sequencing is applicable for the analysis of
      MHC class II-eluted peptides.

PMID- 8299687
TI  - Genetic analysis of immune dysfunction in non-obese diabetic (NOD) mice: mapping
      of a susceptibility locus close to the Bcl-2 gene correlates with increased
      resistance of NOD T cells to apoptosis induction.
AB  - The non-obese diabetic (NOD) mouse strain provides a remarkable model for
      investigating the mechanisms of autoimmunity. Independent genetic analyses of
      this model have previously shown that chromosome 1-linked loci were involved in
      the control of periinsulitis and sialitis on the one hand and of insulitis and
      diabetes on the other hand. In the present work, analysis of a [NOD x (NOD x
      C57BL/6)F1] backcross progeny allowed us to clearly dissociate two genetic
      regions: one was associated with periinsulitis and mapped to the middle region of
      chromosome 1, in the vicinity of the Bcl-2 gene; the other was associated with
      insulitis and mapped to the proximal part of the chromosome. Three intermediate
      markers D1Mit18, D1Mit5 and D1Mit19 covering at least 25 centiMorgans between
      these two regions, were associated with neither periinsulitis nor insulitis. The
      role of the Bcl-2-linked region in the immune anomalies of NOD mice was further
      investigated in a (NOD x C57BL/6)F2 cross where the Bcl-2nod haplotype was linked
      to elevated serum levels of IgG (p < 0.0005). The middle region of chromosome 1
      is, therefore, involved in the control of three phenotypes, including
      periinsulitis, sialitis and hyperIgG, pointing to Bcl-2 as a good candidate for a
      cause of the NOD mouse disease. Consistent with the anti-apoptotic function of
      the Bcl-2 gene product, activated T lymphocytes from NOD mice showed a markedly
      increased resistance to induction of apoptosis following deprivation of
      interleukin-2 when compared to those from non-autoimmune strains. After the
      recent observation of the Fas gene alterations in the lpr and lprcg mutations,
      these findings indicate that deregulation of lymphoid cell apoptosis may be a
      general pathogenetic mechanism in autoimmune diseases.

PMID- 8299688
TI  - A quantitative assay to measure the interaction between immunogenic peptides and
      purified class I major histocompatibility complex molecules.
AB  - A direct and sensitive biochemical assay to measure the interaction in solution
      between peptides and affinity-purified major histocompatibility complex (MHC)
      class I molecules has been generated. Specific binding reflecting the known class
      I restriction of cytotoxic T cell responses was obtained. Adding an excess of
      beta 2-microglobulin (beta 2m) significantly increased the rate of peptide
      association, but it did not affect the rate of dissociation. Binding was
      complicated by a rapid and apparently irreversible loss of functional MHC class I
      at 37 degrees C which might limit the life span of empty MHC class I thereby
      preventing the inadvertent exchange of peptides at the target cell surface. All
      class I molecules tested bound peptides of the canonical octa- to nona-meric
      length. However, one class I molecule, Kk, also bound peptides, which were much
      longer suggesting that the preference of class I molecules for short epitopes is
      not absolute and may be caused by factors other than the peptide-MHC class I
      binding event itself.

PMID- 8299689
TI  - Transcriptional regulation of the gene for the second component of human
      complement: promoter analysis.
AB  - The 5' flanking region of the human gene for the second component of complement
      was sequenced and analyzed functionally. RNase protection demonstrated a cluster
      of four initiation sites in the 5' flanking region utilized in the hepatoma cell
      line, HepG2. Utilization of all four initiation sites increased in response to
      gamma-interferon (IFN-gamma). Transient transfection analysis was used to examine
      cis-acting sequence motifs controlling transcription from the 5'-flanking region.
      We identified a 228-bp minimal promoter fragment which was able to direct basal
      and IFN-gamma inducible transcription from authentic initiation sites. Sequence
      motifs outside of this region may modulate the transcriptional regulation of the
      second component of complement. Although complement components are not
      coordinately regulated, we identified four regions of significant homology with
      the promoters of multiple other complement components. Three of these regions
      were within the minimal promoter fragment.

PMID- 8299690
TI  - Evidence for a stromal cell-dependent, self-renewing B cell population in
      lymphoid follicles of the ileal Peyer's patch of sheep.
AB  - Lymphoid follicles of the ileal Peyer's patch (PP) of young sheep function as the
      major source of B cells and a site of immunoglobulin (Ig) receptor
      diversification. However, extensive cell death in culture has restricted
      investigations of ileal PP follicular (iPf)B cell biology. We investigated the
      possibility that sustained iPfB cell proliferation may require an interaction
      with mesenchymal stromal cells (SC). Four SC lines, cloned from lymphoid
      follicles of the ileal PP, and various sheep and xenogeneic mesenchymal cells
      were used to characterize the nature of iPfB cell-SC interactions. A sustained
      proliferative response was unique to iPfB cells, required iPfB cell-SC contact,
      and SC membranes functioned as intact SC to either enhance or inhibit iPfB cell
      proliferative responses. The iPfB cell proliferation in SC co-cultures was
      accompanied by extensive cell death and a slow decline in viable cell number.
      Flow cytometric analysis confirmed that viable lymphocytes, present in SC co
      cultures, were immature B cells that expressed surface IgM, with either lambda or
      kappa. Ig light chain, and that SC co-culture inhibited iPfB cell
      differentiation. Finally, addition of soluble anti-sheep Ig to iPfB cell-SC co
      cultures did not inhibit SC-dependent iPfB cell proliferation or iPfB cell
      binding to SC. These data indicate that an interaction between specific SC
      membrane molecules and non-Ig molecules of iPfB cells either supported or
      inhibited a self-renewing proliferative response by immature (sIgMLo, BAQ44A-)
      iPfB cells. Finally, SC-dependent iPfB cell proliferation was independent of T
      cells and extrinsic antigen which further suggests that a functionally distinct B
      cell population resides in lymphoid follicles of the ileal PP.

PMID- 8299691
TI  - Profound reduction in allergen sensitivity following treatment with a novel
      allergy vaccine.
AB  - A novel approach is described for the treatment of IgE-mediated allergic
      reactions which is based on the induction of a strong anti-IgE response in the
      host. Vaccination of ovalbumin-sensitized rats with constant domains two and
      three of rat IgE coupled to a heterologous carrier protein resulted in a profound
      decrease in serum levels of IgE, and later in a nearly complete block of
      histamine release from mast cells and basophils upon challenge with either a
      cross-linking polyclonal anti-IgE antiserum or a specific allergen.

PMID- 8299692
TI  - A new mutation, aly, that induces a generalized lack of lymph nodes accompanied
      by immunodeficiency in mice.
AB  - We have found a new spontaneous autosomal recessive mutation in mice that causes
      a systemic absence of lymph nodes and Peyer's patches. The name "alymphoplasia",
      with the gene symbol "aly", is proposed for this mutant. The spleen of aly/aly
      mice is devoid of well-defined lymphoid follicles, and the thymus does not show a
      clear cortical-medullary distinction. The mutant homozygotes are deficient in
      both humoral and cell-mediated immune functions, and are highly susceptible to
      infections. They have a reduced level of IgM and severely depressed levels of IgG
      and IgA in their sera, and do not reject allogeneic skin grafts. However, they
      have mature T and B cells as determined from their cell surface antigens. The
      results of bone marrow transplantation experiments suggest a mesenchymal disorder
      as a possible cause of the lack of lymph nodes and of immunodeficiency in the aly
      mouse. The aly mutant mouse may be a useful animal model of primary
      immunodeficiency, as are the nu (nude) and scid (severe combined
      immunodeficiency) mice.

PMID- 8299693
TI  - Human monocytes are stimulated for nitric oxide release in vitro by some tumor
      cells but not by cytokines and lipopolysaccharide.
AB  - Nitric oxide (NO) has been recently identified as a potent mediator of
      tumoricidal activity of activated macrophages. Macrophages can be activated for
      tumor cell killing by microbial products, including lipopolysaccharide (LPS) and
      various cytokines. Here we report that in contrast to mouse macrophages, human
      peripheral blood monocytes stimulated with cytokines or LPS failed to release NO.
      Also priming of monocytes with interferon-gamma followed by activation with
      cytokines or LPS did not cause NO secretion. However, monocytes responded with NO
      production to stimulation with some human cancer cells but not with untransformed
      cells. NO production by monocytes was inhibited by NG-monomethyl-L-arginine,
      specific inhibitor of NO synthase and emetine, an irreversible blocker of protein
      synthesis. This may imply that human monocytes are unique in their restricted
      capacity to produce NO following interaction with some tumor cells, but not with
      other stimulators, and in this respect they may be able to distinguish between
      malignant and normal cells.

PMID- 8299694
TI  - Differential effects of superantigen-induced "anergy" on priming and effector
      stages of a T cell-dependent antibody response.
AB  - The in vitro T cell nonresponsiveness or anergy to restimulation with
      staphylococcal enterotoxin B (SEB) following the in vivo injection of the
      superantigen is well characterized. Here we use mice transgenic for a V beta 8.2+
      T cell receptor (TcR) (reactive with SEB) to establish a large population of
      anergic T cells in vivo. As expected, peripheral T cells from the SEB injected
      transgenic mice failed to proliferate or produce interleukin (IL)-2 following
      restimulation with the superantigen in vitro. However, in this system
      superantigen reactivity could be restored by either addition of exogenous IL-2,
      or stimulation with immobilized anti-TcR antibody. To evaluate the effects of
      superantigen-induced anergy in vivo, SEB-injected or noninjected control
      transgenic mice were immunized and boosted with the T cell-dependent antigen
      tetanus toxin (TT). SEB injection of the V beta 8.2+ transgenic mice 5 days prior
      to the TT immunization inhibited the anti-TT antibody response as measured over a
      100-day period, whereas injection of a superantigen which does not interact with
      the V beta 8.2% TcR (such as SEA) did not. Furthermore, SEB injection of control
      nontransgenic mice did not interfere with the induction of a high titer anti-TT
      antibody response. In contrast to the inhibition seen when SEB was given prior to
      TT immunization, injection of transgenics with SEB either after the priming TT
      immunization or after the recall booster injection did not significantly
      influence the titers of anti-TT antibodies produced. These results demonstrate
      that the establishment of peripheral T cell anergy to superantigens inhibits the
      specific antigenic priming of helper T cells in vivo, but does not prevent primed
      T cells from helping B cells to mount an effective antibody response.

PMID- 8299695
TI  - B cell emigration directly from the cortex of lymphoid follicles in the bursa of
      Fabricius.
AB  - In the peripheral blood (PBL) of juvenile chickens three populations of B cells
      have previously been distinguished based on life-span and origin of cells within
      each population. In this report we show that the largest PBL B cell subset,
      population 1 B cells, which are short-lived cells corresponding to about 60% of
      PBL B cells and the vast majority of bursal emigrants, exit from the bursa
      directly from the follicular cortex. This conclusion is based on the specific
      labeling of rapidly dividing cortical lymphocytes with bromodeoxyuridine,
      followed by their detection in the periphery prior to the appearance of
      bromodeoxyuridine labeled cells in the bursa medulla. Furthermore, the rate of
      emigration of cortical lymphocytes, 1.00 +/- 0.1% of PBL B cells per hour, is
      indistinguishable from the emigration rate of B cells from the bursa as a whole.
      The anatomical organization of the bursa has evolved to focus gut-derived
      antigens from the bursal lumen into the lymphoid follicles. The emigration of
      cortical bursal cells is discussed in relation to the exposure of bursal
      lymphocytes to extrinsic antigen.

PMID- 8299696
TI  - The functional state of follicular dendritic cells in severe combined
      immunodeficient (SCID) mice: role of the lymphocytes.
AB  - In the present study, we have investigated the capacity of follicular dendritic
      cells (FDC) to trap immune complexes (IC) in the splenic white pulp of severe
      combined immunodeficient (SCID) mice and the influence of lymphocyte transfer on
      FDC function. FDC are absent in the splenic white pulp of naive SCID mice as
      revealed by in vitro IC trapping assay. One week after transfer of syngeneic
      lymphocytes, functional FDC with complement receptors appeared in the primary
      follicles coincident with B cell segregation, and IC were trapped on those FDC in
      a complement-dependent manner. Next, we immunized the reconstituted SCID mouse to
      see whether another type of FDC could be induced in the secondary follicle.
      Antigenic stimulation induced FDC with an additional capacity to capture IC via
      FcR gamma II. As seen in immunocompetent mice, this type of FDC was located only
      in the light zone of the secondary follicle. The newly generated FDC did not
      carry H-2 antigen of transferred lymphocytes from F1 mice. In SCID mice, in which
      normally no functional FDC are detectable, the microenvironments of the splenic
      white pulp have a capacity to develop and differentiate normally after transfer
      of lymphocytes. Apparently, the generation of functional IC-trapping FDC causes
      the induction of complement receptor(s) and Fc receptor on meshwork cells, which
      requires the presence of the lymphocytes.

PMID- 8299697
TI  - The use of antibody-secreting cell probes to reveal tissue-restricted immune
      responses during infection.
AB  - Antibody secreting cell probes (ASC-probes) were generated from the hepatic lymph
      node (HLN), mesenteric lymph node (MLN) and spleen of rats after infection with
      the liver fluke, Fasciola hepatica, and used to probe Western blots of parasite
      antigens. In chronic primary infections, parasite-specific antibodies were only
      detected in ASC-probes derived from HLN. Seven days after a secondary infection,
      a restricted response was detected in ASC-probes from the MLN, directed
      predominantly against an antigen specific to the newly excysted juvenile (NEJ)
      stage. This NEJ-specific antigen was only recognized by HLN if the second
      infection was not rejected and the challenge flukes reached the liver.
      Measurement of the immunoglobulin levels present in the ASC-probes showed
      significant elevation only in lymph nodes draining sites of recent infection. In
      addition, when the isotype profiles were determined in ASC-probes derived from
      different lymph nodes, it was observed that they showed different isotype
      preferences, in particular IgA for the MLN, IgE for HL.N and IgM for spleen.
      These results show that discrete and independent immune responses occur in
      different body compartments of a rat against different stages of a parasite.

PMID- 8299698
TI  - Interleukin-2 (IL-2) receptor gamma chain mutations in X-linked severe combined
      immunodeficiency disease result in the loss of high-affinity IL-2 receptor
      binding.
AB  - Interactions of interleukin-2 (IL-2) with its high-affinity, heterotrimeric
      receptor (IL-2R alpha beta gamma) play a pivotal role in the autocrine pathway of
      T lymphocyte expansion required in an immune response. Mutations in the IL-2R
      gamma chain-encoding gene have been found in SCIDX1, a primary immunodeficiency
      characterized by the absence of T cell and NK cell development. We have
      investigated six unrelated SCIDX1 patients for molecular abnormalities of the IL
      2R gamma gene. A variety of defects were identified, including the absence of
      transcripts, frame-shift deletions and point mutations within canonical cytokine
      receptor motifs (conserved cysteines and the "WS" box). The ability of these
      mutated IL-2R gamma chains to participate in the function of a high-affinity IL
      2R complex was examined by radiolabeled IL-2 binding studies using Epstein-Barr
      virus-transformed B lymphoblastoid cell lines (B-LCL) derived from SCIDX1
      patients. Although normal control B-LCL express high-affinity IL-2 binding sites
      (Kd = 60 pM, 150 sites/cell), B-LCL derived from SCIDX1 patients failed to bind
      IL-2 under high-affinity conditions. These SCIDX1 mutations confirm the critical
      role of the IL-2R gamma chain in T cell and NK cell development. In addition,
      these data provide insight into the structure/function relationship of the IL-2R
      gamma chain by identifying residues required for the formation of a high-affinity
      IL-2R complex.

PMID- 8299699
TI  - Central tolerance: clonal deletion or clonal arrest?
AB  - Studies in various experimental animals have shown that developing T cells with
      specificity for self antigens can be prevented from maturation at an early stage
      of development. While several in vitro and in vivo experiments have shown that
      the mechanism of silencing autospecific T cells is the deletion of immature
      CD4+8+ thymocytes other experiments were interpreted to indicate that tolerance
      could also result from developmental arrest of more immature CD4-8+ thymocytes
      not involving cell death. Here we show that immature CD4-8+ cells when confronted
      with T cell receptor ligands in vitro neither survive nor differentiate into
      cells which cannot be deleted, indicating that clonal elimination rather than
      developmental arrest is the mechanism of central tolerance of all immature T
      cells.

PMID- 8299700
TI  - Delay in expression of a mammary tumor provirus is responsible for defective
      clonal deletion during postnatal period.
AB  - A gene-encoding ligand for deletion of T cells bearing TcRV beta 6 and V beta 8.1
      cosegregates a new mammary tumor provirus locus, Mtv-50 in NC mice. The sequence
      of the open reading frame (ORF) in the 3' long terminal repeat (LTR) of Mtv-50
      was strikingly similar to those of Mtv-7, Mtv-43 and exogenous mouse mammary
      tumor virus (SW) with properties of minor lymphocyte stimulating antigen 1a.
      Consistent with previous reports, clonal deletion of mature thymocytes bearing
      TcRV beta 6 was defective during the early postnatal period of mice carrying Mtv
      50. Appreciable levels of mRNA corresponding to common Mtv ORF and Mtv-6 ORF were
      expressed in the neonatal thymus, while little, if any, mRNA corresponding to Mtv
      50 ORF was detected in the thymus at the early postnatal stage. Delay in
      expression of Mtv-50 ORF during the postnatal period may be responsible for the
      failure of clonal deletion of V beta 6-T cells in the early postnatal life of
      mice carrying Mtv-50.

PMID- 8299701
TI  - Selective expansion of activated V delta 4+ cells during experimental infection
      of mice with Leishmania major.
AB  - Previous work from this laboratory has revealed that infection of mice with
      Leishmania major leads to an expansion of gamma delta+ T cells in the spleen.
      Further examination of the gamma delta+ T cells expanding in infected mice has
      shown that the majority of these cells in the spleen, lymph nodes, blood and
      liver expressed the V delta 4 gene segment. Cell cycle analysis, using propidium
      iodide incorporation, demonstrated that while only 1% of alpha beta+ T cells in
      the spleen were in either S + G2/M phase, up to 10% of the gamma delta+ T cells
      were in cycling phase 8 weeks after infection. Comparison of the state of
      activation of the two populations in different organs after infection, confirmed
      that gamma delta+ T cells are actively dividing in lymph nodes, liver and blood,
      but not in the thymus or among intraepithelial lymphocytes. Examination of the
      expression of different activation markers on the surface of gamma delta+ T cells
      in the spleen of both normal and chronically infected BALB/c mice by FACS
      analysis, revealed increased expression of LFA-1, CD25, CD44, 4F2, CD28 and the
      heat-stable antigen, whereas Thy-1 and CD5 decreased. Collectively, these results
      suggest an oligoclonal expansion and activation of gamma delta+ T cells in
      response to L. major infection.

PMID- 8299702
TI  - Entrainment of nocturnal pituitary-adrenocortical activity to sleep processes in
      man--a hypothesis.
AB  - The 24 hr patterns of plasma ACTH and cortisol concentrations are characterized
      by prominent circadian and ultradian oscillations. Usually both, nadir and
      acrophase of the circadian rhythm occur during sleep. This led us to re-evaluated
      the temporal relationship between sleep processes and nocturnal plasma ACTH and
      cortisol levels and the impact of several types of sleep manipulation (sleep
      delay, sleep disruption, sleep prolongation, sleep deprivation, and reversal of
      the sleep-wake cycle). Pituitary-adrenocortical activity appeared to be linked to
      the cyclic process of nocturnal sleep with inhibitory influences present during
      the first two sleep cycles. After initiation of the third sleep cycle stimulatory
      effects of sleep prevailed, lasting until awakening. The sleep associated
      influences appeared to act in concert with influences of circadian oscillators
      and resulted in an amplification of the circadian rhythm of pituitary-adrenal
      activity; they were strong enough to entrain the circadian rhythm of the
      pituitary-adrenal system to the sleep-wake cycle, as long as phase delays were
      moderate. However, with acute sleep-wake reversals the sleep associated
      influences were masked by the dominant effects of the circadian clock. In
      contrast, GH secretion appeared to be controlled primarily be sleep-associated
      mechanism with only minor circadian influences.

PMID- 8299703
TI  - Opioid-dopaminergic interactions in primary empty sella.
AB  - Previous studies have indicated different abnormalities of PRL secretion in
      patients with primary empty sella (PES). Since it is known that endogenous
      opiates and dopamine interact in modulating PRL secretion, we have studied the
      effect of an opiate receptor blockade (with Naloxone, NAL, 1.6 mg/h as a
      continuous infusion) on anterior pituitary hormones and on PRL responsiveness to
      metoclopramide (MCP), in 10 premenopausal normoprolactinemic patients with PES,
      studied in follicular phase, in order to investigate neurotransmitter
      abnormalities present in such a syndrome. NAL failed to significantly affect LH
      and FSH basal levels; on the contrary, slight but significant increases in PRL
      and GH secretion were observed. NAL partially blunted the PRL responsiveness to
      the dopaminergic blockade, which was very marked when tested after MCP alone.
      These data confirm that the modulation of anterior pituitary hormone secretion is
      different in PES patients, when compared with normal subjects. The infusion of
      NAL induced a "paradoxical" increase in hormones (PRL and GH) which are normally
      stimulated by endogenous opiates; but, on the other side, it blocked the marked
      PRL responsiveness to the dopaminergic blockade, which is characteristic of PES
      syndrome. This phenomenon seems to indicate that the relationships between
      dopaminergic and opiatergic neurons could be modified by the neuroanatomic
      alteration which is present in this complex syndrome.

PMID- 8299704
TI  - Tumors of the sellar region mimicking pituitary adenomas.
AB  - In the sellar region most tumors of our collection (n = 1937) are pituitary
      adenomas, followed by craniopharyngiomas, chordomas and meningiomas. Difficulties
      in morphological differential diagnosis by light microscopy may occur in
      meningiomas, plasmacytomas, chordomas and germinomas. In these cases,
      immunohistological investigations and sometimes even electron microscopy are
      helpful in solving the problems. Meningiomas can sometimes resemble pituitary
      adenomas. Of diagnostic value in these cases is the expression of vimentin and S
      100-protein in the meningioma cells. Plasmacytomas may also mimic pituitary
      adenomas. In these cases, the positive reaction with antibodies against LCA and
      immunoglobulins or against kappa-light-chains and lambda-light-chains leads to
      the diagnosis. Chordomas, too, can sometimes be hardly distinguished from
      pituitary adenomas. In these cases, the expression of S-100-protein, vimentin and
      CEA by the chordoma cells and the typical electron microscopic features of
      chordomas are helpful for the differential diagnosis. Germinomas may sometimes be
      indistinguishable from lymphocytic hypophysitis. Of diagnostic importance are
      here the expression of HCG and placental alkaline phosphatase by germinoma cells.
      In the above mentioned cases, it is also important to perform immunohistochemical
      examinations for pituitary hormones including alpha-subunit. All these tumors do
      not express these hormones.

PMID- 8299705
TI  - The stimulatory effect of pituitary adenylate cyclase activating polypeptide
      (PACAP) on LH release from rat pituitary cells in vitro does not involve calcium
      mobilization.
AB  - The hypothalamic peptide "pituitary adenylate cyclase activating polypeptide
      (PACAP)" stimulates cAMP production in cultured rat pituitary cells and enhances
      LH release. It has been suggested that the stimulation of LH release by PACAP
      comprises two distinct mechanisms: a direct stimulatory action on LH secretion
      and a potentiation of the response of the gonadotrophes to LHRH. Thus the
      possibility exists that PACAP may enhance LH secretion not only by increased cAMP
      production but also by increasing cytosolic Ca2+ concentrations ([Ca2+]). In the
      present study we examined whether PACAP affects cytosolic [Ca2+] in identified
      rat gonadotrophes (as determined by the fura-method) and whether the suggested
      potentiating effect of PACAP on LHRH induced LH release is dependent on Ca2+.
      PACAP (1 nM) and 0.1 nM LHRH significantly increased LH concentrations in the
      culture medium after 5 hrs of incubation. Coincubation of cells with both
      peptides resulted in an additive increase of LH release. While the stimulatory
      effect LHRH was blunted in Ca(2+)-free medium, PACAP remained stimulatory to LH
      release. PACAP stimulated cAMP formation regardless whether the culture medium
      contained Ca2+ or not. Gonadotrophes were selected by their response to LHRH (1
      microM) and were subsequently challenged with PACAP (1 microM). About 75% of
      gonadotrophes responded also to PACAP with an increase of cytosolic [Ca2+] which
      was blunted by removal of extracellular Ca2+. We suggest that in the rat
      pituitary the majority of the gonadotrophes are PACAP responsive as determined by
      an increase of cytosolic [Ca2+].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299706
TI  - Endocrine markers in malignant tumor cells producing parathyroid hormone-related
      protein.
AB  - Humoral hypercalcemia of malignancy may reflect the synthesis and secretion of
      biologically active parathyroid hormone-related protein (PTHrP) by a given tumor.
      In the present study we investigated 25 human non-endocrine carcinomas which were
      clinically associated with hypercalcemia (Ca > 11 mg%). By applying PTHrP
      specific immunocytochemistry, PTHrP could be detected in all tumors. The intra
      tumorous distribution was heterogeneous with strong positivity in relatively few
      cells or weak positivity in the majority of cells. Surprisingly, in the PTHrP
      producing cells none of the marker proteins typical of endocrine cells (neuron
      specific enolase, Leu-7 antigen, chromogranin, synaptophysin and endocrine
      granule constituent) was found. On the other hand, PTHrP producing cells of
      endocrine origin, such as medullary cancer, or normal and adenomatous parathyroid
      glands, all produce these endocrine markers. Thus for the first time, the
      existence of peptide hormone producing tumor cells is reported without expression
      of endocrine markers. This indicates a special mechanism of PTHrP secretion.

PMID- 8299707
TI  - Time course of changes in free thyroid indices, rT3, TSH, cortisol and ACTH
      following exposure to sulfur mustard.
AB  - In order to evaluate the time course of changes in serum concentration of thyroid
      hormones, cortisol and ACTH in patients exposed to chemical weapons containing
      sulfur mustard, we measured serum concentrations of hormones on the first, third
      and fifth week following injury in 13 soldiers and compared them to the results
      obtained from 34 control men. Free T4 and T3 indices were decreased and rT3,
      cortisol and ACTH were increased in the first week following exposure. There was
      a subnormal TSH response to TRH in 2 of 3 men tested. Except for an increase in
      FT4I and a decrease in TSH by the third week, and a steady decline in serum
      cortisol, serum hormone concentrations were unchanged until the fifth week after
      injury. The decline in serum cortisol occurred despite a constant increase in
      serum ACTH. By the fifth week only 1 of 13 men had serum cortisol levels > 10
      micrograms/dl. We conclude that exposure to chemical weapons containing sulfur
      mustard results in alterations in serum concentrations of thyroid and adrenal
      hormones and ACTH, resembling changes seen in burn trauma. Some evidence of
      direct effects of mustard on endocrine glands exist.

PMID- 8299708
TI  - On the diversity of insulin secretion and sensitivity in subjects with impaired
      glucose tolerance.
AB  - Insulin secretion and sensitivity are basic characteristics determining the
      glucose tolerance. The aim of this study was to investigate if derangements in
      these two main characteristics were generally found in subjects with impaired
      glucose tolerance (IGT). The early insulin response at the intravenous glucose
      tolerance test (IVGTT) in 42 subjects with IGT was found to be correlated to the
      glucose tolerance (r = -0.38, p < 0.01 vs, fasting glucose and r = 0.35, p <
      0.02, vs the k-value of IVGTT) while fasting insulin was found to be closely
      correlated to insulin sensitivity, measured by the euglycemic clamp method (r = 
      0.83, p < 0.003, n = 11). Using data obtained at the IVGTT's in the IGT subjects,
      different patterns of insulin secretion were found representing different
      combinations of impairments in insulin secretion and sensitivity. However, in the
      majority of the IGT subjects a marked decrease in the early insulin response and
      a fasting hyperinsulinemia were found. The present study suggest such a
      characterization by the IVGTT to be of importance for a better understanding of
      the dynamic interplay between insulin secretion and sensitivity in IGT subjects.

PMID- 8299709
TI  - Increased plasma endothelin-1 concentrations in E. coli septic peritonitis rats
      with diabetes mellitus.
AB  - To study the diabetic mellitus (DM) patient's reaction to sepsis, we investigated
      the survival rate, the bacteremia, plasma endotoxin and plasma endothelin-1
      levels in E. coli septic peritonitis rats with or without streptozotocin-induced
      DM. No significant difference could be detected between the DM and nondiabetic
      rats in the survival rate, the bacteremia level or the plasma endotoxin level.
      The DM rat manifested a significant increase compared to the nondiabetic rat in
      the plasma endothelin-1 level four hours after the outbreak of peritonitis.
      Endothelin-1 may thus play some role in the E. coli septic peritonitis rat with
      DM.

PMID- 8299710
TI  - Successful treatment of ectopic Cushing's syndrome with the long-acting
      somatostatin analog octreotide.
AB  - We report on the efficacy of the long-acting somatostatin analog octreotide in a
      43-yr old woman with ectopic ACTH syndrome. Plasma cortisol, ACTH, beta-endorphin
      (beta-END) and urinary free cortisol (UFC) were elevated (range 743-920 nmol/l,
      29.2-49.7 pmol/l, 71.0-84.1 pmol/l, 2117-3119 nmol/day respectively). Ovine CRH
      (oCRH) and high dose dexamethasone did not affect cortisol and ACTH levels, while
      UFC significantly decreased after dexamethasone. Initially radiological
      investigation failed to localize the ACTH secreting tumor. Ketoconazole was not
      tolerated. Plasma cortisol significantly decreased both after single (100
      micrograms sc) (baseline 531 nmol/l, nadir 218 nmol/l) and 3-day octreotide
      administration (from 810 to 448 nmol/l); plasma ACTH decreased slightly (from
      30.4 to 21.3 pmol/l and from 32.4 to 22.5 pmol/l respectively); UFC decreased
      from 2616 to 711 nmol/day after the 3-day test. Long-term octreotide treatment
      (100 micrograms/8h per 54 weeks) led to clinical and biochemical improvement and
      recurrence followed drug withdrawal; no side effects were observed. Six months
      after octreotide administration a 2 cm lung mass was detected with CT and MR.
      Surgery was performed and a bronchial carcinoid was removed. Immunoreactive ACTH
      in the tumor has been demonstrated by histochemistry. Postoperatively a lasting
      remission of Cushing's syndrome was observed without further therapy.

PMID- 8299711
TI  - Levothyroxine suppressive therapy in the medical management of nontoxic benign
      multinodular goiter.
AB  - The aim of this investigation was to evaluate the efficacy of levothyroxine
      suppressive therapy in the medical management of nontoxic benign multinodular
      goiter. We studied 104 patients with multiple (2 to 5, mean = 2.5 +/- 0.7), solid
      (96%) or predominantly solid (4%), nonfunctional (68%) or hypofunctional (32%)
      thyroid nodules. The benign (colloid) nature of 94% of the nodules was confirmed
      by fine-needle aspiration biopsy. All the patients received suppressive (2.2
      micrograms per Kg body weight) daily oral doses of levothyroxine for 6 months. To
      confirm the effectiveness of the suppressive therapy, TSH levels were measured by
      an ultrasensitive immunometric assay at 3 and 6 month of treatment. For each
      patient, the volume of each nodule before and after levothyroxine therapy was
      evaluated by high-resolution ultrasonography. After 3 and 6 months of treatment,
      TSH levels were suppressed (lower than 0.1 mIU/l) in 75 patients and detectable
      in 29. At the end of the study, the volume of all the nodules was decreased by
      50% or more (responder group) in 20/75 (27%) of the patients with suppressed TSH
      levels, and in 3/29 (10%) of those with detectable TSH values. In the latter
      group the proportion of patients in which one or more nodule(s) showed an
      increase in volume (48%) was significantly higher (p < 0.0005) than in patients
      with suppressed TSH (29%). We can conclude that an effective TSH suppressive
      therapy is an useful tool in the treatment of nontoxic benign multinodular
      goiter.

PMID- 8299712
TI  - The labelling of proliferating cells by Ki67 and MIB-1 antibodies depends on the
      binding of a nuclear protein to the DNA.
AB  - The antigen Ki-67 Ag, regarded as a marker for proliferating cells, was
      identified as a protein(s) (pKi-67) which can exist free or associated with DNA
      as evidenced by DNA digestion of cells before or after immunolabeling with Ki-67.
      The dual nature of this antigen was also supported by reconstitution of Ki-67 Ag
      from purified DNA and nuclear proteins extracted from the K562 cell line. The
      immunoreactivity of the resulting complexes was examined in solution using Ki-67
      and MIB-1 antibodies. The interaction between Ki-67 or MIB-1 antibodies and pKi
      67 was enhanced in the presence of undegraded ds DNA, indicating that ds DNA
      modulates the conformation of pKi-67 and that the altered conformation of pKi-67
      is more reactive than the pure protein to both Ki-67 and MIB-1 antibodies.

PMID- 8299713
TI  - Coculture modulates laminin synthesis and mRNA levels in epidermal keratinocytes
      and dermal fibroblasts.
AB  - To investigate the role of cell-cell interactions between keratinocytes and
      fibroblasts at the dermal-epidermal junction in the regulation of extracellular
      matrix protein expression, we have developed a cell coculture model that allows
      both cell types to interact on a reciprocal basis and yet be isolated as pure
      populations for quantitative analysis. Using porous membrane inserts as a
      substrate for keratinocytes grown in coculture over fibroblast monolayers, we
      report that coculture stimulates cell growth and total protein synthesis in both
      cell types when compared to monocultured controls. Both keratinocytes and
      fibroblasts synthesize laminin B1 and B2 chains with an additional subunit
      comigrating with laminin M chain detected in keratinocytes but only faintly
      visible in fibroblasts. Laminin A chain synthesis could not be detected. Although
      laminin subunit composition did not change in either cell type, fractional
      laminin synthesis increases by 41.0 +/- 2.3% in cocultured keratinocytes and
      decreases by 73.8 +/- 8.1% in cocultured fibroblasts when compared to
      monocultured controls. In cocultured keratinocytes, steady-state mRNA levels for
      laminin B1, B2, and M chains increased by 69.4, 63.5, and 136.8%, respectively,
      when compared to monocultured controls. However, in cocultured fibroblasts,
      laminin B1 and B2 chain mRNA decreased by 74.2 and 72.7%, respectively. Laminin M
      chain mRNA could not be detected in fibroblasts. These results suggest that
      synthesis and expression of laminin is regulated through reciprocal cell-cell
      interactions in fibroblasts and keratinocytes grown in coculture.

PMID- 8299714
TI  - Interleukin-1 and transforming growth factor-alpha: synergistic stimulation of
      metalloproteinases, PGE2, and proliferation in human fibroblasts.
AB  - Wound healing and other inflammatory processes are driven by a complex series of
      interactions among cells, the extracellular matrix, and secreted products of
      various cell types. Cytokines, such as interleukin-1 and transforming growth
      factor-alpha, are present at wound sites and contribute to the proinflammatory
      milieu of these sites. In the present study, we have investigated the effect of
      these cytokines, individually and in concert, on fibroblast expression of matrix
      metalloproteinases, which contribute to extracellular matrix remodeling, and of
      prostaglandin E2, which alters vascular tone and permeability. The
      metalloproteinases, procollagenase (matrix metalloproteinase-1) and
      prostromelysin (matrix metalloproteinase-3), are induced by exposure of dermal
      fibroblasts to interleukin-1, not stimulated by transforming growth factor-alpha,
      but are synergistically induced by the combination of cytokines. The 92-kDa type
      IV procollagenase (matrix metalloproteinase-9, progelatinase B), is also
      stimulated in synergistic fashion. Prostaglandin E2 is induced in rheumatoid
      synovial fibroblasts by interleukin-1 beta, not altered by transforming growth
      factor-alpha, and is synergistically released by the combination of the two
      cytokines. Fibroblast proliferation, which is also a component of normal wound
      healing, is also synergistically stimulated by the action of the two cytokines in
      concert. These results indicate that interleukin-1 beta and transforming growth
      factor-alpha synergize to elicit a number of phenotypic responses in fibroblasts
      which are relevant to normal wound healing and chronic inflammation.

PMID- 8299715
TI  - Production of interleukin-1 by primary cultured parenchymal liver cells
      (hepatocytes).
AB  - The production of interleukin-1 (IL-1) by cultured parenchymal liver cells was
      revealed by a biological assay with an IL-1-dependent cell line, Northern blot
      analysis, and in situ hybridization. Inhibition experiments on the IL-1 activity
      with anti IL-1 alpha antibody also support the presence of IL-1 alpha in the
      supernatant of cultured parenchymal liver cells. Based on these results, we
      discuss the possibility of IL-1 production by parenchymal liver cells in vivo.

PMID- 8299716
TI  - Heat shock glycoprotein GP50: product of the retinoic acid-inducible J6 gene.
AB  - High intracellular levels of heat shock proteins and enhanced protein
      glycosylation are two phenomena closely associated with the cellular stress
      response. GP50 is the major heat-induced glycoprotein in Chinese hamster ovary
      (CHO) cells; however, GP50 is not well characterized, and its function is
      unknown. J6 is a gene originally identified in F9 murine teratocarcinoma cells
      after exposure to retinoic acid. In this study we show that J6 is heat-inducible
      and codes for a protein that shares characteristics with GP50. Western blotting
      of CHO cell homogenates, using a J6 polyclonal antibody, showed a single band
      with a molecular weight identical to that of GP50. Thermotolerant cells showed
      increased levels of the J6/GP50 protein. Heat-shocked CHO cells also accumulated
      transiently high levels of J6 mRNA between 2 and 7 h following 10 min at 45
      degrees C. These induction kinetics are similar to those for GP50 labeling with D
      [3H]mannose and to the activation of major heat shock genes, e.g., hsp70. Hybrid
      selection of J6 mRNA from CHO cells, followed by in vitro translation, produced a
      single band on SDS-PAGE with a molecular weight identical to that of
      deglycosylated GP50. Neither cellular proliferation (exponential growth versus
      plateau phase) nor the specific heat shock temperature (41.5 degrees C versus 45
      degrees C) had significant effects on J6 induction by heat stress. Stress
      conditions other than hyperthermia, including ethanol, arsenite, and hypoxia,
      increased J6 mRNA levels. Conversely, J6 mRNA was reduced by quercetin, brefeldin
      A, okadaic acid, uv, and hydrogen peroxide. Our data support the hypothesis that
      J6 is a heat shock gene with a gene product identical to the polypeptide moiety
      of GP50.

PMID- 8299717
TI  - Analysis of the factors involved in the retinoic acid-induced differentiation of
      a retinoid-hypersensitive embryonal carcinoma cell mutant.
AB  - Retinoic acid (RA) has been known to play an important role in cellular growth
      and differentiation as well as in vertebrate development. Many in vitro cell
      cultures also respond to RA by differentiating. Perhaps the most widely studied
      of these cultures are embryonal carcinoma (EC) cells. We have used an RA
      hypersensitive EC cell mutant, created by retroviral insertion, to analyze the
      activity of the identifiable components in the RA response pathway. We have
      analyzed the mRNA expression patterns of the retinoic acid receptors (RARs)
      alpha, beta, and gamma, the retinoid X receptors (RXRs) alpha, beta, and gamma,
      and the cellular retinoic acid binding proteins (CRABPs) I and II. Our results
      indicate that CRABP I, RAR beta, and RAR gamma mRNAs are expressed differentially
      between parent and RA-hypersensitive mutant cells. All three messages are present
      at higher basal levels and at earlier times after RA addition in the mutant
      relative to parental cells. All other elements examined are equivalently
      expressed. Therefore analyses of the expression patterns of CRABPs, RARs, and
      RXRs in these RA-hypersensitive cells point to the probable importance of CRABP
      I, RAR beta, and RAR gamma in the RA induction pathway and also indicate that
      CRABP II and RXR gamma are not likely to be critical elements in the early
      differentiative response of cells to RA.

PMID- 8299718
TI  - Kinetic studies on phagocytosis and lysosomal digestion of rod outer segments by
      human retinal pigment epithelial cells in vitro.
AB  - Using novel methodology, this study describes the kinetics of rod outer segment
      (ROS) phagocytosis and digestion by human retinal pigment epithelial (RPE) cells
      in vitro and examines the effect of certain lysosomal enzyme inhibitors on ROS
      digestion in these cells. Human RPE cells displayed saturation of phagocytosis
      with respect to both ROS concentration and time. While surface-binding and
      ingestion phases of ROS phagocytosis saturated after 24-36 h, the rate of ROS
      digestion reached a maximal level within 24 h. Increasing the concentration of
      zinc in the culture medium from 1.9 to 100 microM had no significant effect on
      ROS digestion. The effects of swainsonine (an alpha-mannosidase inhibitor),
      pepstatin (an aspartic protease inhibitor), and leupeptin (a cysteine protease
      inhibitor) were also examined. At 6 h, ROS digestion was reduced 27.3 +/- 15.3%
      by swainsonine, 69.4 +/- 20.9% by pepstatin, and 77.0 +/- 14.4% by leupeptin. The
      effect of these inhibitors declined with increasing time. This study is the first
      to demonstrate the functional importance of cysteine and aspartic proteases in
      the digestion of ROS by RPE cells in vitro.

PMID- 8299719
TI  - Interactions between cells and collagen V molecules or single chains involve
      distinct mechanisms.
AB  - Acid-soluble and pepsin-treated collagen V were prepared from fetal human bones
      or human placenta, respectively, to be tested for potential cell adhesion
      promoting activity. Out of 14 different collagen I-adhering cell lines, 10 showed
      distinct adhesion to collagen V. In all cases adhesion was followed by spreading.
      The activities of intact and pepsin-solubilized collagen V were similar,
      suggesting that the cell binding sites are restricted to the triple-helical
      domain of the molecules. Cell adhesion was also induced by the unfolded form of
      collagen V and after separation of the alpha chains by heparin affinity
      chromatography. Isolated alpha 2(V) chains, rich in RGD sequences, were more
      efficient than isolated alpha 1(V) chains. However, cell adhesion to native or
      denatured collagen V did not proceed by the same molecular mechanisms as shown by
      cell adhesion inhibition experiments. Cell adhesion to native collagen V was
      insensitive to the presence of RGD-containing synthetic peptides while adhesion
      to denatured collagen V was inhibited by the peptides. Furthermore, the results
      strongly suggested a major role for alpha 1 beta 1 and alpha 2 beta 1 integrins
      in the RGD-independent cell adhesion to native collagen V. These data indicate
      that collagen V is a specific adhesive substrate for different cell types. It
      also suggests that distinct sets of RGD-dependent and RGD-independent receptors
      mediate cell attachment to unfolded and native collagen V, respectively. This
      mechanism is shared by at least the interstitial collagens I and VI, which
      supports the hypothesis that when included in the triple-helical conformation of
      collagens, RGD sequences are either not accessible to cells or exhibit specific
      conformations recognized by different integrins.

PMID- 8299720
TI  - Recombinant bone morphogenetic protein-4, transforming growth factor-beta 1, and
      activin A enhance the cartilage phenotype of articular chondrocytes in vitro.
AB  - Bone morphogenetic protein-4 (BMP-4) is a member of the transforming growth
      factor-beta (TGF-beta) supergene family and is characterized by its ability to
      induce singly de novo cartilage and bone in vivo. The influence of recombinant
      bone morphogenetic protein-4 and some related members, TGF-beta 1, activin A, and
      inhibin A, on articular chondrocyte metabolism in the presence and absence of
      extracellular matrix has been examined. BMP-4 and TGF-beta 1 stimulated [35S]
      sulfate incorporation in a dose-dependent manner in short-term monolayer,
      micromass, and explant cultures. Activin A showed a slight but significant
      stimulation of proteoglycan synthesis while inhibin A decreased metabolic
      activity. The effects observed were most pronounced in the explant culture
      system. Although the relative influence of the growth factors was less apparent
      in chondrocytes isolated from adult cartilage, the qualitative responses were
      similar with cells obtained from young animals. The maintenance and enhancement
      of the cartilage phenotype was further investigated by Northern blot analysis.
      BMP-4 and TGF-beta 1 increased the levels of expression of type II collagen and
      proteoglycan aggrecan in short-term cultures, while activin A and inhibin A did
      not affect these parameters significantly when compared to serum-free control
      cultures. Binding experiments with 125I-BMP-4, revealed the presence of specific,
      high-affinity binding sites with an apparent dissociation constant of 110 pM and
      about 6000 receptors per cell. Chemical cross-linking showed the presence of
      three components (apparent size 200, 90, and 70 kDa), demonstrating the presence
      of functional receptors for BMP-4 on primary articular chondrocytes.

PMID- 8299721
TI  - Dystrophin (Xp21), a new phenotype marker of cultured rat aortic myocytes.
AB  - Dystrophin is a low-abundance cytoskeletal protein involved in the maintenance of
      membrane integrity in striated muscle. Very little is known about its role in
      smooth muscle. Utrophin (a dystrophin-related protein) is an ubiquitous protein
      whose role is still unclear. Changes in the expression of both proteins (if any)
      during phenotypic modulation of smooth muscle have not yet been reported. In
      contrast, modulated expression of heavy-molecular-weight caldesmon (h-CaD), a
      well-known specific regulatory protein of the contractile apparatus in smooth
      muscle, is well documented, along with its nonmuscle isoform, low-molecular
      weight caldesmon (1-CaD), and other cytoskeletal proteins. We investigated three
      properties of cultured rat aortic smooth muscle cells: morphology, contractile
      ability, and expression of dystrophin, utrophin, h-CaD, and 1-CaD. Cells were
      grown either in serum substitute supplemented medium (U-medium), where they
      reexpressed contractility, or in fetal calf serum-supplemented medium (F-medium),
      where they did not. It was found that only cultures grown in U-medium continued
      expressing dystrophin, even during the proliferation phase, contrary to cells
      grown in F-medium. However, when F-medium was changed for U-medium the cells
      recovered their contractility and reexpressed dystrophin. Expression of utrophin,
      h-CaD, and 1-CaD was similar in both culture types. Dystrophin was demonstrated
      to be a true phenotype marker of cultured rat aortic smooth muscle cells,
      particularly with respect to their actual contractility.

PMID- 8299722
TI  - Enhancement of CDDP cytotoxicity by caffeine is characterized by apoptotic cell
      death.
AB  - The ability of caffeine, an agent that suppresses cell replication by inhibiting
      deoxyribonucleic acids (DNA) repair, to modulate the cytotoxicity of cis
      diamminedichloroplatinum (CDDP) was investigated in murine lymphoma cell line EL
      4. EL-4 cells were precultured with or without 20 micrograms/ml CDDP for 1 h and
      then cultured in the presence of 5 mM caffeine up to 48 h after reseeding. In
      CDDP-pretreated cells, suppression of cell growth and decrease in cell viability
      from 24 h were observed. Cell cycle arrest in G2 + M phase and a concomitant
      increase in both rhodamine 123 (R123) uptake and cell size (forward scatter) were
      observed in these cells. Treatment with caffeine alone suppressed growth rate,
      R123 uptake, cell size, and frequency of S phase fraction in the cell cycle.
      Combination of the two agents, CDDP+caffeine, strongly suppressed not only cell
      viability but also R123 uptake and cell size, compared with CDDP pretreatment
      alone. DNA histogram analysis by flow cytometry revealed that cultivation with
      caffeine hastened G2 + M arrest in CDDP-pretreated cells by reduction in the time
      of passing through S phase. DNA fragmentation was observed following incubation
      of CDDP-pretreated cells with caffeine for 16 h when marked accumulation in G2 +
      M phase was observed. The intensity of these ladder fragments increased in a time
      related manner. These results demonstrate that enhancement of cytotoxic activity
      against CDDP-treated cells by caffeine is characterized by an acceleration of DNA
      degradation in G2 + M phase, namely apoptotic cell death. The fact that induction
      of DNA fragmentation during G2 + M phase by caffeine modulates the cytotoxicity
      of CDDP may give rise to a new combination regime of chemotherapy against
      malignant tumor cells.

PMID- 8299723
TI  - Metalloproteinase-dependent neurite outgrowth within a synthetic extracellular
      matrix is induced by nerve growth factor.
AB  - In order to assess the requirement for matrix metalloproteinases in neuronal
      regeneration, in vitro neurite outgrowth by chick dorsal root ganglionic neurons
      (DRGn) was examined within a reconstituted extracellular matrix. For these
      studies, cultured neurons were treated with a synthetic peptide inhibitor of
      metalloproteinases (spIMP), LMHKPRCGVPDVGG. spIMP inhibited all neuronal
      metalloproteinase activities in zymography and substrate-release assays and was
      used to examine the role of metalloproteinases in neurite outgrowth by DRGn.
      Cultures of dissociated DRGn rapidly extended neurites on planar extracellular
      matrix substrates and this rate of outgrowth was not affected by adding NGF or
      spIMP. In contrast, neurite extension within a three-dimensional gel of
      extracellular matrix increased nearly threefold after adding NGF. The NGF-induced
      neurite penetration was negated in the presence of spIMP but not by control
      peptide. Similar results were obtained using explanted dorsal root ganglia. These
      findings suggested that NGF-induced neurite outgrowth within an extracellular
      matrix involves metalloproteinase activity. Zymographic analysis of media
      conditioned by NGF-treated DRGn revealed a pair of gelatinolytic bands with
      apparent molecular masses 72 and 66 kDa, which comigrated as a single 66-kDa band
      after activation with an organomercurial agent. The gelatinase activities were
      calcium- and zinc-dependent and were absent from zymograms developed in the
      presence of spIMP, indicating that NGF-treated DRGn release and activate a 72-kDa
      metalloproteinase. Samples from DRGn cultures treated with low levels of NGF
      contained similar amounts of latent and activated metalloproteinase, while high
      levels of NGF induced an apparent increase in total metalloproteinase secretion
      and a substantially greater proportion of activated enzyme. Western blot analysis
      showed this metalloproteinase was immunologically similar to 72-kDa type IV
      collagenase and immunoassays revealed that this matrix metalloproteinase was
      increased threefold by high NGF. Furthermore, after high NGF treatment, DRGn
      media contained sixfold more metalloproteinase activity in assays of matrix
      degradation. In summary, these results indicate that NGF enhanced
      metalloproteinase-dependent neurite outgrowth of DRGn within a reconstituted
      extracellular matrix. Also, NGF increased the expression and activation of 72-kDa
      type IV collagenase, suggesting a role for this matrix-degrading
      metalloproteinase in neuronal regeneration.

PMID- 8299724
TI  - Microinjection technique: routine system for characterization of microcapillaries
      by bubble pressure measurement.
AB  - Five tubing types with different outer and inner diameter dimensions were used to
      pull injection capillaries with different openings. The correlation between
      threshold bubble pressure and tip inner and outer diameter was established for
      each type of tubing. Statistical analysis revealed that the bubble pressure is an
      accurate measure for the tip inner diameter independent of the tubing used to
      pull the capillary. A graph directly relating the tip inner diameter to the
      threshold bubble pressure is presented. The tip outer diameter could not be
      related to the bubble pressure for tubings of different size. This diameter
      depends on the wall thickness of the tubing and the puller configuration. Data on
      the inner tip diameter were used to test the relationship between volume released
      from injection capillaries and their tip radius. It was found that the volume
      increases with the fourth power of the radius. Strategies for optimizing the
      injection capillary are discussed.

PMID- 8299725
TI  - Expression of three alternative acetylcholinesterase messenger RNAs in human
      tumor cell lines of different tissue origins.
AB  - To study the molecular mechanisms underlying the intensive expression of
      acetylcholinesterase (AChE) in different tumor types, we characterized levels and
      composition of its messenger RNA (mRNA) sequences in heterologous tumor cell
      lines, primary tumor biopsies, and normal fetal and adult tissues and determined
      their exon-intron origin within the corresponding ACHE gene. Reverse
      transcription followed by polymerase chain reaction (RT-PCR) revealed three
      alternatively spliced ACHE mRNAs in NT2/D1 teratocarcinoma, NCI-N-592 small cell
      lung carcinoma, TE671 medulloblastoma, K-562 erythroleukemia, and 293 transformed
      embryonal kidney cells. The three ACHE mRNAs include the principal species
      expressed in brain and muscle and two additional transcripts containing
      insertions of 751 or 829 residues downstream from the exon 4 domain. The inserted
      region, which represents an intron in brain and muscle, is expressed in the tumor
      cell lines either as a "readthrough" form or with 78 residues deleted from its 5'
      end. A major band of 2.5 kb was labeled with ACHE cDNA in poly(A)+ RNA blots from
      medulloblastoma cells or brain tissue, whereas a PCR-amplified probe from the
      inserted domain labeled a 3.4-kb band but not the 2.5-kb band in poly(A)+ RNA
      from small cell lung carcinoma. The ACHE mRNAs including the alternative
      insertions were found only in cell lines with levels of the principal ACHE mRNA
      species equal to or higher than those in brain (1-10 molecules/cell), determined
      by following the kinetics of mRNA PCR amplification. Genomic DNA sequencing
      revealed that the inserted domains in the ACHE mRNAs expressed in the tumor cell
      lines encode C-terminal peptides of 40 and 14 residues. These include a free
      cysteine, terminate with the consensus HG element, and continue by a 29-residue
      long C-terminal hydrophobic cleavable peptide, properties characteristic of
      precursors to phosphoinositide (PI)-linked proteins. In extension of the reported
      expression of PI-linked AChE in hemopoietic cells including K-562, our findings
      demonstrate the existence of ACHE mRNAs with the potential to encode one
      hydrophilic and two PI-linked forms of AChE in tumor cells from both hemopoietic
      and nonhemopoietic origins.

PMID- 8299726
TI  - Localization of protein kinase C isozymes in cardiac myocytes.
AB  - Activation of protein kinase C (PKC) isozymes is associated with their
      translocation from the cell-soluble fraction to the cell-particulate fraction,
      presumably near their protein substrates. Therefore, identifying the subcellular
      localization of each activated PKC isozyme may help to elucidate its role in
      cardiac functions. In the present work, we have determined the subcellular
      localization of six PKC isozymes (alpha, beta I, beta II, delta, epsilon, and
      zeta) in nonstimulated cardiac myocytes and in myocytes stimulated by
      norepinephrine (2 microM) or phorbol 12-myristate 13-acetate (100 nM). Activated
      PKC isozymes were localized in various subcellular compartments such as inside
      the nucleus and on myofibrils. The presence of serum in the growth medium also
      caused a redistribution of PKC isozymes in the cells distinct from that obtained
      with cells cultured in defined medium. We suggest that isozyme-specific
      localization may determine phosphorylation of different protein substrates
      present at these respective translocation sites and the resulting PKC-mediated
      cellular responses.

PMID- 8299727
TI  - Ultrastructural localization of filamentous actin within neuronal interphase
      nuclei in situ.
AB  - Previous biochemical studies utilizing isolated nuclei and nuclear matrices have
      shown actin to be a constituent of the interphase nucleus. In addition, recent
      ultrastructural work has shown the presence of actin and myosin within nuclei of
      interphase cells in situ. It was unclear, however, whether this intranuclear
      actin is present in the unpolymerized globular actin or the filamentous (F)-actin
      form. The present work, using confocal microscopy and ultrastructural
      cytochemical techniques, demonstrates the presence of F-actin within interphase
      nuclei of intact, uncompromised, dorsal root ganglion neurons in vitro and in
      vivo. Labeling by FITC-phalloidin detected the presence of intranuclear F-actin
      adjacent to the nucleolar periphery in a small fraction of cells in vitro, an
      observation confirmed by three-dimensional reconstruction. Ultrastructural
      analyses of cells exposed to heavy meromyosin (HMM), showed the presence of
      typical "arrowhead" complexes. The observation that these complexes were
      associated with nucleoli confirms that the intranuclear ligand detected by FITC
      phalloidin indeed represents F-actin. Postembedding labeling with HMM conjugated
      to 20-nm colloidal gold (HMM-Au20) resulted in labeling similar to that obtained
      with HMM. However, HMM-Au20 was found to label a much larger fraction of cells,
      both in vitro and in vivo, than did FITC-phalloidin or HMM. This finding
      indicates that labeling with HMM-Au20 more accurately reflects the extent of
      actin polymerization in nuclei. Results from double labeling with HMM-Au20 and an
      antibody to alpha-sarcomeric actin confirmed that only a small amount of nuclear
      actin is in the F-form. Together, these results represent a first ultrastructural
      demonstration of the presence of F-actin in nuclei of neurons. While the role of
      nuclear F-actin has yet to be defined, the results suggest that F-actin may
      represent a component of the molecular motor responsible for the dynamic
      positioning of specific chromatin domains into the tissue-specific, nonrandom
      patterns observed in many cell types.

PMID- 8299728
TI  - Discrete localization of different DNA topoisomerases in HeLa and K562 cell
      nuclei and subnuclear fractions.
AB  - Monoclonal antibodies raised against DNA topoisomerase I and against
      topoisomerase II alpha and beta isoforms, which have been previously demonstrated
      to be highly specific and capable of detecting cell cycle-related variations of
      the topoisomerase II isoforms (Negri et al., 1992, Exp. Cell Res. 200, 452-459),
      have been utilized for a fine subcellular localization. Immunocytochemistry by
      confocal and electron microscopy have been used for a topological and
      quantitative evaluation of the fine distribution of the different topoisomerases
      in HeLa and K562 cells. Topoisomerase I and topoisomerase II alpha are present
      both in the nucleoplasm and in the nucleolus, though at different relative
      ratios, while topoisomerase II beta is exclusively present at the nucleolar
      level. This is further confirmed by immunoblotting and immunocytochemical
      quantitative evaluations performed on purified nuclear matrix fractions obtained
      from K562 cells. In fact, the amount of topoisomerase I and topoisomerase II
      alpha present in the whole cell nuclei is partly lost in isolated nuclei but,
      while topoisomerase I is further significantly reduced in nuclear matrix
      preparations, the topoisomerase II alpha content is only slightly decreased. On
      the other hand, the great majority of topoisomerase II beta is retained in the
      nuclear matrix and can be detected exclusively in association with the nucleolar
      remnant. These results are consistent with specific functional roles hypothesized
      for the different topoisomerase types.

PMID- 8299729
TI  - Different fate of sibling cells upon inhibition of transcription in G1.
AB  - In normally cycling populations of NIH3T3 cells, both sibling cells generated by
      a mitotic division require similar periods of time for completion of the cell
      cycle, with variations (intersibling times) of < or = 3 h for > 90% of the
      population. In this study, we analyzed by time-lapse video recording the effect
      of the RNA polymerase II inhibitor alpha-amanitin on the intersibling times of
      cells exposed to the drug at defined postmitotic ages. Our results led to the
      identification of three subpopulations of NIH3T3 cells. In the first one, both
      sibling cells were highly sensitive to alpha-amanitin. These cells were exposed
      to the inhibitor at a postmitotic age of < or = 2 h. The second subpopulation was
      composed of cells where one sibling showed normal kinetics of cell cycle
      progression, while the other sibling had an increased cell cycle length
      (intersibling times of up to 12 h) or did not divide at all during the period of
      observation. These cells were 2-8 h old at the time of treatment. In the third
      subpopulation, representing cells at later stages in the cell cycle, no
      significant increase in intersibling times was observed. These data indicate that
      alpha-amanitin increases the intersibling times of cells exposed to the drug
      during G1. In addition, our results suggest that the variable-length period of
      G1, thought to be located in late G1, is dependent on RNA polymerase II
      transcription.

PMID- 8299730
TI  - Expression of two different products of CDC25Mm, a mammalian Ras activator,
      during development of mouse brain.
AB  - The CDC25Mm gene codes for Ras-guanine nucleotide exchange factors. Four
      different full-length cDNA clones derived from the same gene and coding for
      proteins of different sizes that have in common the last 661 amino acids have
      been isolated from mouse brain. In order to investigate the expression of the
      products of this gene in different tissues we have prepared two polyclonal
      antibodies directed toward two different regions of the protein comprised in the
      last C-terminal 472 amino acids. While in most of the tested tissues we have been
      unable to definitely identify CDC25Mm products, in NIH3T3 fibroblasts we have
      found a poorly expressed 120-kDa protein. In the mouse brain we have identified
      two proteins of 140 and 58 kDa. While the former is expressed in the adult mouse,
      the latter is present in the embryo and persists for few days after birth. This
      finding suggests that differential expression of various forms of CDC25Mm may be
      involved in brain development.

PMID- 8299731
TI  - A common megakaryocytic and erythrocytic precursor in murine erythroleukemia
      (Friend) cells?

PMID- 8299732
TI  - Megakaryocytic and erythrocytic cell lines share a common precursor cell.

PMID- 8299733
TI  - Differential responses of fetal, neonatal, and adult myelopoietic progenitors to
      interferon and tumor necrosis factor.
AB  - Human fetal liver (FL) and neonatal cord blood (CB) granulocyte-monocyte colony
      forming progenitor cells (GM-CFC) are unique in their physiological environment
      and in certain proliferative and differentiative capacities. Tumor necrosis
      factor (TNF) and interferon (IFN) may inhibit or stimulate the growth of human
      bone marrow GM-CFC in vitro. The effects of recombinant human (rh) TNF-alpha,
      rhIFN-alpha, and rhIFN-tau on recombinant human granulocyte-macrophage colony
      stimulating factor (rhGM-CSF)-stimulated clonogenic cultures of day 7 GM-CFC from
      FL and umbilical CB were compared with rhGM-CSF-stimulated GM-CFC from normal
      human bone marrow (BM). We demonstrate that, in comparison to BM progenitor
      cells, GM-CFC from both FL and CB were highly resistant to growth inhibition by
      all three cytokines. Furthermore, clonogenic growth of progenitors from FL and CB
      was markedly potentiated by IFN-tau in GM-CSF-stimulated cultures and was
      stimulated by IFN-tau in the absence of GM-CSF. Depletion of potential accessory
      cells resulted in a marked stimulatory response of CB cells to TNF-alpha, in the
      presence of GM-CSF, while it did not alter the responses to IFN. The stimulatory
      effects of IFN-tau and TNF-alpha may be indirectly mediated, at least in part,
      through induction of increased GM-CSF production and increased GM-CSF receptor
      expression by fetal cells. Divergent responses of myelopoietic cells, derived
      from various hematopoietic compartments, to regulatory actions of cytokines may
      provide a basis for further understanding the role of the environment in
      maturation and differentiation of granulocytes and monocytes.

PMID- 8299734
TI  - Radioprotection of hematopoietic stem cells by interleukin-1.
AB  - Radioprotective agents such as interleukin-1 (IL-1) and tumor necrosis factor
      (TNF-alpha), when given prior to irradiation, protect animals from radiation
      damage. However, in vivo administration of these cytokines does not allow one to
      determine whether the protective effects act directly on the hematopoietic
      system. In the present study, we subjected male bone marrow cells to in vitro
      treatment with IL-1 prior to irradiation and bone marrow transplantation. We
      found that male bone marrow cells pretreated with IL-1 prior to irradiation
      increased the survival of irradiated female recipient mice when compared with
      nontreated irradiated marrow cells. In addition, irradiated female recipients
      that received IL-1-pretreated male donor bone marrow cells displayed an increased
      presence of male donor cells in their bone marrow, spleen, and thymus for up to 3
      months posttransplant. Furthermore, serial transplantation studies revealed that
      male cells could only be detected in tertiary female recipients who received bone
      marrow from mice transplanted with IL-1-treated cells. These results indicate
      that IL-1 pretreatment protects both short-term and long-term repopulating stem
      cells from an irradiation insult and that these cells are capable of
      reconstituting the myeloid and lymphoid organs of recipient mice.

PMID- 8299735
TI  - Interleukin-10 promotes the growth of megakaryocyte, mast cell, and multilineage
      colonies: analysis with committed progenitors and Thy1loSca1+ stem cells.
AB  - The growth-promoting activities of interleukin-10 (IL-10) were assessed in
      hematopoietic colony-forming assays. We found that IL-10 failed to support the
      clonal growth of normal and lineage-depleted (Lin-) bone marrow (BM) cells.
      Furthermore, IL-10 neither enhanced nor suppressed colony formation by
      eosinophil, neutrophil, or macrophage progenitors when combined with a variety of
      factors. IL-10 stimulated a modest increase in erythropoietin (Epo)-dependent
      erythroid colonies but had no effect on the burst-promoting activities of IL-3.
      However, the combination of IL-10 plus IL-3 resulted in the enhanced growth of
      mast cell progenitors. In addition to its mast cell stimulating activity, IL-10
      promoted the growth of megakaryocyte (Mk) and Mk-mixed colonies when combined
      with Epo or with Epo plus IL-3, IL-6, or IL-11. Comparative studies showed that
      the megakaryocyte potentiating activity of IL-10 is roughly equivalent to that of
      IL-6 and IL-11. In experiments using Thy1loSca1+ stem cells, IL-10 was shown to
      enhance the number of cells initiating IL-3-dependent colony formation. IL-10
      also costimulated increased colony formation when used with IL-3 and another
      factor such as IL-1, IL-6, and granulocyte colony-stimulating factor (G-CSF).
      Cellular analysis of the resulting colonies indicated that IL-10 increases the
      formation of multilineage colonies containing erythrocytes, megakaryocytes,
      and/or mast cells. The ability of IL-10 to cooperatively regulate various stages
      of hematopoietic development is discussed.

PMID- 8299736
TI  - Effects of 5-fluorouracil or total-body irradiation on murine bone marrow
      microvasculature.
AB  - This study was designed to investigate the changes in the murine bone marrow
      microvasculature following treatment with 5-fluorouracil (5-FU) or total-body
      irradiation (TBI). Seventy 8- to 12-week-old C3H male mice received either 5-FU
      at a dose of 150 mg/kg intravenously (i.v.) or TBI at a dose of 8 Gy in two
      fractions 4 hours apart. Femurs from the treated mice were studied by vascular
      casting, using mercox, and by routine histology at days 5, 21, and 90. On day 5,
      the sinusoids were markedly swollen, and many were fused with one another. This
      was accompanied by significant reduction in the bone marrow cellularity. The
      central sinus was grossly dilated in both TBI- and 5-FU-treated groups. The
      pronounced sinusoidal dilatation on day 5 appears to be a mechanical effect due
      to hematopoietic cell loss resulting in relative negative pressure outside the
      sinusoids. On day 21, the sinusoidal swelling had subsided, and the overall
      vascular volume appeared to be restored to normal. However, there was a large
      variation in the shape and size of the sinusoids, and those present were not
      uniformly distributed. This may be due to the result of mechanical pressure from
      the reconstituted hematopoietic cells. Whether these changes in the shape and
      distribution of sinusoids have functional significance--for instance, release of
      the hematopoietic cells into the circulation--remains to be established.

PMID- 8299737
TI  - Interleukin-6 and erythropoietin act as direct potentiators and inducers of in
      vitro cytoplasmic process formation on purified mouse megakaryocytes.
AB  - Mouse megakaryocytes were purified using a rabbit antimouse platelet serum, and
      magnetic beads were conjugated with an antirabbit IgG antibody. The purified
      cells were 95.8 +/- 1.2% megakaryocytes, and the recovery and viability of the
      megakaryocytes were 70 +/- 18.4%, and 80 +/- 13.4%, respectively. The effects of
      recombinant erythropoietin (Epo), interleukin-6 (IL-6), and IL-1 beta on these
      purified megakaryocytes were studied. Epo and IL-6 significantly increased DNA
      synthesis in these cells, but IL-1 beta did not. Similarly, both Epo and IL-6,
      but not IL-1 beta, increased the acetylcholinesterase (AchE) activity in the
      megakaryocytes. Epo and IL-6 stimulated the megakaryocytes to form cytoplasmic
      processes, which are considered to represent in vitro proplatelet formation. This
      process formation was inhibited by the addition of colchicine to the cultures. It
      was concluded that Epo and IL-6 are not only direct potentiators of
      megakaryocytes, but also inducers of in vitro cytoplasmic process formation on
      megakaryocytes.

PMID- 8299738
TI  - Infection with a Kirsten-retrovirus can induce a multiplicity of tumorigenic
      phenotypes in the interleukin-3-dependent FDC-P1 cells.
AB  - The identification of ras oncogenes in both human and animal tumors as well as in
      preleukemic and precancerous lesions suggests that activated ras genes
      participate in neoplastic development, yet the precise role of ras oncogenes in
      leukemogenesis is not clear. To assess the functional role of ras genes in
      tumorigenesis, we introduced with a retroviral vector either a wild-type (Gly-12)
      or a mutant (Val-12) Kirsten ras cDNA into the cells of a factor-dependent
      myeloid cell line, FDC-P1. FDC-P1 cells are nontumorigenic and their
      proliferation is dependent on either interleukin-3 (IL-3) or granulocyte
      macrophage colony-stimulating factor (GM-CSF). The Ki-Val 12-infected FDC-P1 cell
      population is still strictly IL-3-dependent but has acquired the ability to
      survive up to 72 hours in the absence of growth factor and to form tumors in nude
      mice. These tumors are easily established into cell lines that are clonal and
      show a multiplicity of phenotypes with respect to their growth factor dependence.
      These results suggest that, in contrast with the overexpression of a normal Ki
      ras, Ki-ras oncogene can efficiently promote the tumorigenic conversion of FDC-P1
      cells. However, the clonality of the tumors as well as the distinct phenotypes
      indicates that other genetic events are required for tumorigenicity. Therefore,
      in FDC-P1 cells, an activated ras gene acts as a dominant oncogene through the
      induction of tumor progression. Finally, in this simple experimental system we
      observed a multiplicity of tumorigenic phenotypes which are reminiscent of those
      observed in patients with acute myeloid leukemia.

PMID- 8299739
TI  - Myelosuppressive effects in vivo with very low dosages of monomeric recombinant
      murine macrophage inflammatory protein-1 alpha.
AB  - Macrophage inflammatory protein (MIP)-1 alpha has
      myelosuppressive/myeloprotective effects in vivo in mice. We recently reported
      that > 99.7% of recombinant murine (rm) MIP-1 alpha polymerizes rapidly at
      relatively high concentrations in physiological salt solution, and it is the
      monomeric form of MIP-1 alpha that is active in vitro as a myelosuppressive
      factor. Polymerized MIP-1 alpha is inactive in this effect and does not block the
      myelosuppressive action of monomeric MIP-1 alpha. MIP-1 alpha could be maintained
      in monomeric form in physiological saline if diluted to low concentrations. This
      led us to reevaluate the actual amounts of MIP-1 alpha necessary for
      myelosuppression in vivo. C3H/HeJ mice were injected intravenously (i.v.) with
      monomeric rmMIP-1 alpha or control diluent and effects were evaluated on
      progenitor cells--multipotent colony-forming units (CFU-GEMM), burst-forming
      units-erythroid (BFU-E), and colony-forming units-granulocyte/macrophage (CFU-GM)
      -as described in previous studies in which MIP-1 alpha concentrations were used
      that we now know to have been mainly in polymerized form. Monomeric MIP-1 alpha
      rapidly decreased cycling rates and absolute numbers of myeloid progenitor cells
      in marrow and spleen. These effects, which occurred with about 1000-fold less MIP
      1 alpha than we previously reported, were dose-dependent, time-related, and
      reversible. Suppressive effects were noted within 3 hours for cell cycling and
      within 24 hours for absolute numbers of progenitor cells in marrow and spleen and
      were lost by 48 hours. Decreased circulating neutrophils were noted at 48 hours.
      Column-separated polymerized rmMIP-1 alpha was inactive in vivo. These results
      demonstrate the potency of low doses of monomeric MIP-1 alpha in vivo. Since
      clinical administration of large amounts of an agent that is mainly in an
      inactive form may result in severe pharmacological side effects, the information
      presented here is of relevance for potential clinical trials using MIP-1 alpha as
      a myelosuppressive/myeloprotective agent.

PMID- 8299740
TI  - Removal of hematopoietic cells and macrophages from mouse bone marrow cultures:
      isolation of fibroblastlike stromal cells.
AB  - A method is described that permits the removal of hematopoietic cells and
      macrophages from mouse bone marrow cultures. The method is based on the
      difference in effect of extracellular ATP4- ions (ATP in the absence of divalent,
      complexing cations) on cells of hematopoietic origin, including macrophages, and
      of nonhematopoietic origin, such as fibroblastlike stromal cells. In contrast to
      fibroblastlike cells, hematopoietic cells and macrophages form under the
      influence of ATP4- lesions in their plasma membranes, which allows the entrance
      of molecules such as ethidium bromide (EB) and potassium thiocyanate (KSCN),
      which normally do not easily cross the membrane. The lesions can be rapidly
      closed by the addition of Mg2+ to the incubation medium, leaving the EB or KSCN
      trapped in the cell. This method allows the selective introduction of cell-toxic
      substances such as KSCN into hematopoietic cells and macrophages. By using this
      method, fibroblastlike stromal cells can be isolated from mouse bone marrow
      cultures.

PMID- 8299741
TI  - Correction of the enzyme deficiency in hematopoietic cells of Gaucher patients
      using a clinically acceptable retroviral supernatant transduction protocol.
AB  - Gaucher disease is a lysosomal storage disorder caused by a deficiency of the
      enzyme glucocerebrosidase (GC), and is an excellent candidate for gene
      replacement therapy. To develop a clinically acceptable protocol for this
      purpose, we created two amplified (A) high-titer retroviral vector-producer cell
      lines to efficiently transduce hematopoietic stem and progenitor cells.
      GP+envAm12/A-LGSN (A-LGSN), contained the GC cDNA driven by the retroviral long
      terminal repeat (LTR) and the neomycin phosphotransferase gene expressed from the
      simian virus 40 early promoter. GP+envAm12/A-LG4 (A-LG4) contained only the GC
      gene driven by the LTR. Both A-LGSN and A-LG4 contained multiple proviral copies
      and gave approximately 10-fold higher titers on 3T3 cells compared to their
      unamplified counterparts. These vectors were packaged in GP+envAm12 cells because
      vectors produced in this cell line transduced hematopoietic cells more
      efficiently than other packaging cells tested. Bone marrow mononuclear cells and
      purified CD34+ cells were infected with virus supernatants four times in the
      presence of interleukin-3 (IL-3), IL-6, and stem cell factor (SCF) over 96 hours
      in culture. Cells were then plated in semisolid cultures and colony-forming unit
      granulocyte/macrophage (CFU-GM) colonies were scored for vector presence by
      polymerase chain reaction (PCR). Transduction efficiency of CFU-GM colonies
      derived from CD34+ cells was improved considerably using the amplified vectors in
      the GP+envAm12 packaging line. For A-LGSN, A-LG4, and unamplified LGSN,
      transduction efficiencies were 41, 42, and 25%, respectively. Therefore, multiple
      proviral copies resulting in higher titer improves retroviral transduction of
      human hematopoietic progenitor cells. Hematopoietic cells from Gaucher patients
      were transduced and placed into long-term bone marrow culture (LTBMC). Viral
      supernatant from the amplified producer lines transduced long-term culture
      initiating cells (LTCIC) efficiently (30 to 50%) using this clinically acceptable
      protocol. Both sustained mRNA expression and GC enzyme production are achieved in
      the long-term culture of LTCIC and lead to correction of the GC deficiency in
      their progeny cells.

PMID- 8299742
TI  - Immunocytochemical localization of calcineurin in the adult and developing
      primary visual cortex of cats.
AB  - An immunocytochemical method was used to localize calcineurin, a calcium
      dependent calmodulin-stimulated protein phosphatase, in the primary visual cortex
      of developing and adult cats. In the adult calcineurin immunoreactivity exhibits
      a laminar distribution with dense labeling in the upper half of layers II/III and
      two lightly labeled bands in lower layer IV and in layer VI. Most of the
      immunoreactive neurons are pyramidal in shape and appear to form a subpopulation
      of cortical neurons, but non-pyramidal neurons were also labeled, especially
      during early stages of postnatal development. The distribution pattern of
      calcineurin immunoreactivity showed developmental changes until at least 3 months
      of age. The number of calcineurin-positive cells abruptly increased at 3 weeks,
      and heavily labeled neurons appeared in a well-delineated band in layer IV
      between 3 and 5 weeks of age. At 6 to 10 weeks, neurons in layers II/III also
      became strongly immunoreactive. At this developmental stage intensely stained
      cells were thus distributed throughout layers II to IV. Thereafter, there was a
      marked decrease in the number of immunoreactive cells in layer IV and beyond 12
      weeks the distribution pattern of calcineurin immunoreactivity became similar to
      that of adult animals. These changes of calcineurin expression show some relation
      with the inside-out pattern of cortical maturation and with the time course and
      the laminar selectivity of use-dependent malleability. Therefore, we suggest that
      calcineurin may be involved in processes of neuronal differentiation and
      experience-dependent plasticity.

PMID- 8299743
TI  - The medial temporal lobe in encoding, retention, retrieval and interhemispheric
      transfer of visual memory in primates.
AB  - Low-level electrical stimulation through electrodes in the medial temporal lobe
      (MTL) was used to disrupt the performance of chiasm-split macaques working in a
      delayed matching-to-sample (DMS) visual memory task. The stimulation was below
      afterdischarge threshold and did not distract the animals. Nonetheless,
      stimulation caused severe deficits when delivered either during encoding or
      retrieval stages. Substantially less deficit appeared when stimulation was
      delivered during the retention interval. Stimulation levels which led to
      significant disruption on the DMS task had no effect on a discrimination task
      using the same kinds of images. Unilateral electrical stimulation delivered to
      MTL in one hemisphere during encoding and to MTL in the other hemisphere during
      retrieval produced an effective disruption, suggesting that the unilateral
      stimulation during the encoding period disrupts the encoding on that side while
      unilateral stimulation delivered to the opposite side during the retrieval period
      prevents the retrieval of the (now unilateral) memory. This suggestion is
      supported by control experiments in which significantly less disruption was
      caused by unilateral electrical stimulation delivered during both the encoding
      and the retrieval period if the stimulation was delivered to the same side in
      both periods. The electrical stimulation was further used to determine that
      interhemispheric access by one hemisphere to memories placed in the other was
      excellent. This was done, in these split-chiasm monkeys, by using unilateral
      stimulation to limit memory formation to just one hemisphere, then testing
      interhemispheric access by routing the test through the "ignorant" hemisphere
      (using just the ipsilateral eye). Successful interhemispheric access was obtained
      with either the anterior commissure or with the splenium of the corpus callosum
      (the other interhemispheric forebrain pathways having been cut). The electrical
      stimulation was also used to determine that the visual inputs even though
      entering via just one eye and one hemisphere, lead to bilateral memory formation.
      In this case each hemisphere was tested separately during retrieval by delivering
      disruptive levels of the electrical stimulation to the MTL of the other
      hemisphere.

PMID- 8299745
TI  - The dorsomedial frontal cortex of the rhesus monkey: topographic representation
      of saccades evoked by electrical stimulation.
AB  - The dorsomedial frontal cortex (DMFC) of monkeys has been implicated in mediating
      visually guided saccadic eye movements. The purpose of this study was to
      determine whether the DMFC has a topographic map coding final eye position, and
      to ascertain whether this region subserves the maintenance of eye position. The
      DMFC was stimulated electrically while monkeys fixated a target presented
      somewhere in visual space. A series of parametric tests was conducted to
      ascertain the best stimulation parameters to evoke saccades. Electrical
      stimulation typically produced contraversive saccades that converged onto a
      region of space, the termination zone. For some stimulation sites, however,
      stimulation produced ipsiversive saccades. This occurred when the termination
      zone was located straight ahead of the monkey. Convergence onto an orbital
      position was never observed during stimulation of the frontal eye fields (FEF),
      stimulation of which evoked fixed-vector saccades. The latency to evoke a saccade
      from the DMFC varied with fixation position, such that it increased monotonically
      the closer the fix spot was to the termination zone. Moreover, the probability of
      evoking a saccade from the DMFC decreased the closer the fix spot was to the
      termination zone. The latency for evoking a saccade and the probability of
      evoking a saccade from the FEF did not vary with fixation position. Horizontal
      head movements were not evoked from the DMFC while a monkey fixated targets
      presented in different positions of visual space. Moveover, changing the position
      of the head with respect to the body did not change the location of a termination
      zone with respect to the head. The DMFC was found to contain a topographic coding
      of termination zones, with rostral sites representing zones in extreme
      contralateral visual space, and caudal sites representing zones straight ahead or
      ipsilaterally. Furthermore, lateral sites represented zones in upper visual
      space, whereas medial sites represented zones in lower visual space. Once the
      eyes were positioned within a termination zone, further stimulation fixed the
      gaze and inhibited visually evoked saccades. Following release from inhibition,
      which occurred shortly after the end of stimulation, the saccades reached the
      visual target accurately. This shows that the stimulation delayed the execution
      of the saccades without actually aborting their execution. We conclude that the
      DMFC contains a map representing eye position in craniotopic coordinates, and we
      argue that this map is utilized to maintain eye position.

PMID- 8299744
TI  - Brainstem sites for the carbachol elicitation of the hippocampal theta rhythm in
      the rat.
AB  - The effects of brainstem microinjections of carbachol on the hippocampal theta
      rhythm were examined in urethane anesthetized rats. The two most effective theta
      eliciting sites with carbachol were the nucleus pontis oralis (RPO) and the
      acetylcholine-containing pedunculopontine tegmental nucleus (PPT) of the
      dorsolateral pontine tegmentum. RPO injections generated theta at mean latencies
      of 38.5 +/- 70.8 s and for mean durations of 12.9 +/- 5.1 min. Five of seven RPO
      injections gave rise to theta virtually instantaneously, i.e., before the
      completion of the injection. PPT injections generated theta at mean latencies of
      1.7 +/- 1.1 min and for mean durations of 11.9 +/- 6.0 min. Injections rostral or
      caudal to RPO in the caudal midbrain reticular formation (RF) or the caudal
      pontine RF (nucleus pontis caudalis) generated theta at considerably longer
      latencies (generally greater than 5 min) or were without effect. Medullary RF
      injections essentially failed to alter the hippocampal EEG. The finding that
      theta was produced at very short latencies at RPO suggests that RPO, the putative
      brainstem source for the generation of theta, is modulated by a cholinergic
      input. The further demonstration that theta was also very effectively elicited
      with PPT injections suggests this acetylcholine-containing nucleus of the
      dorsolateral pons may be a primary source of cholinergic input to RPO in the
      generation of theta. The hippocampal theta rhythm is a major event of REM sleep.
      The present results are consistent with earlier work showing that each of the
      other major events of REM sleep, as well as the REM state, are cholinergically
      activated at the level of the pontine tegmentum.

PMID- 8299746
TI  - Modularity and parallel processing in the oculomotor integrator.
AB  - The neural signals that hold eye position originate in a brainstem structure
      called the neural integrator, so-called because it is thought to compute these
      position signals using a process equivalent to mathematical integration. Most
      previous experiments have assumed that the neural integrator reacts to damage
      like a single mathematical integrator: the eye is expected to drift towards a
      unique resting point at a simple exponential rate dependent on current eye
      position. Physiologically, this would require a neural network with uniformly
      distributed internal connections. However, Cannon et al. (1983) proposed a more
      robust modular internal configuration, with dense local connections and sparse
      remote connections, computationally equivalent to a parallel array of independent
      sub-integrators. Damage to some sub-integrators would not affect function in the
      others, so that part of the position signal would remain intact, and a more
      complex pattern of drift would result. We evaluated this parallel integrator
      hypothesis by recording three-dimensional eye positions in the light and dark
      from five alert monkeys with partial neural integrator failure. Our previous
      study showed that injection of the inhibitory gamma aminobutyric acid agonist
      muscimol into the mesencephalic interstitial nucleus of Cajal (INC) causes almost
      complete failure of the integrators for vertical and torsional eye position after
      approximately 30 min. This study examines the more modest initial effects.
      Several aspects of the initial vertical drift could not be accounted for by the
      single integrator scheme. First, the eye did not initially drift towards a single
      resting position; rapid but brief drift was observed towards multiple resting
      positions. With time after the muscimol injection, this range of stable eye
      positions progressively narrowed until it eventually approximated a single point.
      Second, the drift had multiple time constants. Third, multiple regression
      analysis revealed a significant correlation between drift rate and magnitude of
      the previous saccade, in addition to a correlation between drift rate and
      position. This saccade dependence enabled animals to stabilize gaze by making a
      series of saccades to the same target, each with less post-saccadic drift than
      its predecessor. These observations were predicted and explained by a model in
      which each of several parallel integrators generated a fraction of the eye
      position command.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8299747
TI  - Neuronal activity related to visual recognition memory: long-term memory and the
      encoding of recency and familiarity information in the primate anterior and
      medial inferior temporal and rhinal cortex.
AB  - Recordings of the activity of 2705 single neurones were made in entorhinal and
      perirhinal cortex, area TG of the temporal lobe, and the inferior temporal cortex
      both during monkeys' performance of a serial recognition memory task using
      complex pictures and when monkeys were shown objects. Responses of 120 (9.7%) of
      the visually responsive neurons recorded were significantly smaller to the second
      than to the first presentations of unfamiliar stimuli. The incidence of such
      responses was highest in perirhinal cortex plus areas TE1 and TE2 of the temporal
      lobe, intermediate in lateral entorhinal cortex and areas TE3 and TG, and lowest
      in other parts of entorhinal and inferior temporal cortex. Response decrements
      were maintained across 20 or more intervening presentations of other stimuli for
      the majority of the neurones tested. Responses of 43 (14.4%) of the visually
      responsive neurones tested were significantly greater to unfamiliar than to
      highly familiar stimuli. Such differential responses were found only in lateral
      entorhinal and perirhinal cortex plus areas TG, TE1, TE2 and TE3. For 6 neurones
      the response difference was significant even when the familiar stimuli had not
      been seen for more than 24 h: such neurones demonstrate access to information
      stored in long-term memory for more than 24 h. Seven familiarity neurones
      signalled information concerning the relative familiarity of stimuli but not
      information concerning how recently they were last seen; 58 recency neurones
      signalled information concerning the recency of presentation of stimuli, but not
      their relative familiarity. Thus certain neurones demonstrate the separable
      encoding of recency and familiarity information. Neurones signalling information
      of use for recognition memory are found in cortex close to the rhinal sulcus
      where lesions result in major deficits in the performance of recognition memory
      tasks. The conjunction of these findings provides strong evidence for the
      importance of these neurones and this cortex for processes (recency and
      familiarity discrimination) necessary for recognition and working memory. The
      possible relation of the neuronal responses to priming memory is also discussed.

PMID- 8299748
TI  - Neurophysiological basis of functional recovery in the neonatal spinalized rat.
AB  - It had been shown previously that, following spinalization of the neonatal rat on
      postnatal day 7 (PN7), at the middle thoracic level, there was spontaneous
      recovery of coordinated stepping in the hindlimbs, enabling the animal to execute
      quadrupedal locomotion, with an ataxic gait. No significant recovery occurred in
      rats that were similarly spinalized on PN14. Despite the functional recovery in
      the PN7 group, their hindlimbs were paralyzed when not in contact with a surface.
      In the present experiments, at 16-18 weeks after spinalization, muscle spindle
      GpIa and cutaneous afferents were tested for functional connectivity to the alpha
      motoneurons (a-MNs) that innervate the right triceps surae (TS) muscles. The
      Hoffmann reflex (H-reflex), the tonic stretch reflex (TSR), and cutaneous
      reflexes were recorded from the right TS muscles in the nonanesthetized,
      intercollicular decerebrate preparation. The H-reflex and the TSR were readily
      elicited from the PN7 animals, but not from the PN14 animals. The PN14
      preparations were characterized by prolonged (> 18 h in 3/8 cases), spontaneous
      discharge of motor units, and prominent M responses. There was widespread,
      bilateral convergence of cutaneous afferents from the hindquarters to the a-MNs
      of the TS muscles in both the PN7 and the PN14 preparations. In the
      nonspinalized, control preparation, only ipsilateral, cutaneous afferents
      activated the right TS a-MNs. These results demonstrate that in the chronic (> 3
      months after spinalization), spinalized PN7 rat, but not in the PN14 rat, there
      is a tight functional connectivity between the hindlimb GpIa afferents and their
      homonymous a-MNs.

PMID- 8299749
TI  - Long-term sensitization and environmental conditioning in terrestrial snails.
AB  - The hypothesis that a long-term increase of behavioural responses in snails (over
      a period of days) might be due to environmental conditioning was examined.
      Training consisted of delivering electric shocks non-contingently with test
      stimuli twice per day for 5 days to freely moving snails on a ball floating in
      water. After training, a significant difference in amplitude of a withdrawal
      reaction to tactile test stimulation appeared between shocked and control snails.
      Responses were significantly facilitated in shocked animals for up to 12 days
      after training, but only if the animals were tested in the environment used for
      training. Testing of the same groups of animals crawling freely on the glass lid
      of a tank in which they lived between experimental sessions revealed no
      difference in responses to the same stimuli between shocked and control snails.
      Injection of the neurotoxin 5,7-dihydroxytryptamine, which selectively impairs
      serotonergic cells, eliminated the differences between shocked and control
      animals. Changing the pH of the water in which the ball floated, by addition of
      citric acid, led to a significant selective increase of responsiveness in snails
      sensitized in this environment relative to the responsiveness of the same snails
      with normal water in the tank. The results suggest that the long-term
      sensitization of withdrawal reactions observed is at least in part a
      manifestation of an associative process, namely environmental conditioning.

PMID- 8299750
TI  - Simultaneous hand tracking does not affect human vergence pursuit.
AB  - In order to find out whether human vergence eye movements are influenced by
      simultaneous hand tracking movements, vergence was studied when sinusoidal
      (expressed in vergence angles) target movements were tracked. The target motion
      was externally generated and the target actually moved in depth. Tracking was
      done by the eyes alone or by the eyes and hand together, in both light and dark
      viewing conditions. Our data show that the target motion was tracked by the eyes
      with a short delay (on average 48 ms), independent of the tracking condition.
      This suggests that vergence modeling should include some predictive mechanism
      similar to that proposed for the smooth pursuit subsystem. Furthermore, in
      contrast to effects on smooth pursuit, simultaneous hand tracking movements did
      not influence vergence eye movements. From this, we argue that the balance
      between smooth pursuit and saccadic eye movements is adjustable and can be
      adapted to the requirements of different tasks.

PMID- 8299751
TI  - Control of human jaw elevator muscle activity during simulated chewing with
      varying bolus size.
AB  - During chewing, a small part of the observed muscle activity is needed for the
      basic open-close movements of the mandible, and additional muscle activity (AMA)
      is needed to overcome the resistance of the food. The AMA consists of two
      contributions: a large peripherally induced contribution, starting after food
      contact and a small anticipating contribution, starting before food contact. We
      investigated whether the latencies of these contributions depend on the expected
      or actual bolus size. Subjects made rhythmic open-close movements near their
      natural chewing frequency controlled by a metronome. This frequency was
      determined while the subjects were chewing gum. Food resistance was simulated by
      an external force, acting on the jaw in a downward direction during part of the
      closing movement. Bolus size was simulated by the jaw gape at which the force
      started. Jaw movement and surface EMG of the masseter and anterior temporal
      muscles on both sides and the suprahyoid muscles were recorded during experiments
      in which the jaw gape at which the force started was varied. The peripherally
      induced contribution to the AMA started about 20 ms after the onset of the force,
      irrespective of the jaw gape at which the force started. It is concluded that the
      onset of this contribution depends solely on food contact in the actual cycle.
      The function of the observed mechanism for jaw elevator muscle control may be to
      enable a highly automatic control of the muscle activity required to overcome the
      resistance of food of different hardness and different size. The onset of the
      anticipating contribution to the AMA showed neither a relationship with the
      actual jaw gape at which force onset occurred nor with the expected jaw gape of
      force onset. It is suggested that the onset of the anticipating AMA is related to
      the jaw gape at the onset of closing. The function of this contribution may be
      the regulation of the mechanical response of the jaw after an expected
      disturbance of the closing movement by food contact, by tuning the muscle
      stiffness to the expected hardness of the food.

PMID- 8299752
TI  - Short-latency subliminal effects of transcranial magnetic stimulation on forearm
      motoneurones.
AB  - The H-reflex technique has been used to evaluate the time-course of the effects
      evoked by transcranial clockwise magnetic stimuli in flexor or extensor carpi
      radialis motoneurones. In six subjects, magnetic stimulation was applied over the
      scalp in the focus for the motor response of those muscles. At intensities below
      motor threshold, a facilitation of the H-reflex started at a conditioning-test
      interval of -4 ms (i.e. when the magnetic stimulus lagged the test stimulus by 4
      ms), reached a peak at about -2 ms and rapidly decayed. At about -1 ms, the decay
      attained a local minimum, which in three subjects had values indicating the
      presence of an inhibition. Thereafter, a second facilitatory phase peaked at
      about +1 ms. By matching the time course with the latency of the cortical muscle
      action potential (CMAP) evoked by suprathreshold magnetic stimulation, it is
      inferred that the motoneuronal discharge coincides with the second peak of
      facilitation and is preceded by 3-4 ms of subliminal excitation. This early
      effect could be brought to threshold by convergence of a subliminal Ia EPSP,
      leading to a reduction of the CMAP latency. The early excitatory effects reported
      above are as fast as those described as following transcranial electrical
      stimulation, and should likewise be considered as monosynaptic.

PMID- 8299753
TI  - Motion transparency and coherence in plaids: the role of end-stopped cells.
AB  - Humans do not confound the motion of shadows cast upon a surface with the motion
      of the surface itself, although schemes that propose recombination of orientation
      selective motion signals into a rigid motion percept of two-dimensional patterns
      would predict that they should do so. We propose a simple scheme that avoids
      recombination and instead attributes perception of two-dimensional pattern motion
      to the activation of orientation-selective end-stopped units that operate on the
      logarithm of the luminance. The proposed units respond to the change of contrast
      along a line, which typically occurs at an intersection. They are not active,
      however, when a shadow border intersects the edge of an object, because contrast
      does not change along either of these edges. Thus, end-stopped units signal the
      motion of transparent intersections weakly or not at all, and the independent
      motions of the shadow border and the object prevail. We tested two implications
      of this scheme, using plaids with variable intersection luminance. First, when
      the intersection luminance was such that it kept the contrast along the
      intersecting lines nearly constant, the sensitivity for the rigid plaid's
      direction of motion was minimal, and the sliding motion of the components
      prevailed. This occurred for light bars on dark backgrounds and for dark bars on
      light backgrounds. Thus, the effect of the intersection's luminance on the
      balance between the percepts of rigid-plaid motion and the motion of sliding
      components was independent of contrast inversion of bar and background. Secondly,
      when thin lines with the same luminance as the bars covered the borders of the
      intersection, the intersection's luminance did not affect the rigid-plaid motion
      percept very much, even when it corresponded to a transparent intersection. This
      indicates that, when the edges of the intersection and those of the bars were not
      collinear, the nulling of the end-stopped units did not occur. This result is in
      line with physiological studies, which showed that the response of an end-stopped
      cell to a line is only partially inhibited when a similar line is presented non
      collinearly with the first in the inhibitory end-zone of its receptive field. Our
      results are consistent with a scheme in which a second stage of motion detectors
      combines signals of orientation-selective end-free and orientation-selective end
      stopped units for perception of the rigid motion of two-dimensional patterns.

PMID- 8299754
TI  - Pattern of monosynaptic heteronymous Ia connections in the human lower limb.
AB  - Changes in the firing probability of single motor units in response to electrical
      stimulation of muscle nerves were used to derive the projections of muscle
      spindle Ia afferents to the motoneurones of various leg and thigh muscles.
      Discharges of units in soleus, gastrocnemius medialis, peroneus brevis, tibialis
      anterior, quadriceps, biceps femoris and semitendinosus were investigated after
      stimulation of inferior soleus, gastrocnemius medialis, superficial peroneal,
      deep peroneal and femoral nerves. Homonymous facilitation, occurring at the same
      latency as the H reflex and therefore attributed to monosynaptic Ia EPSPs, was
      found in virtually all the sampled units. In many motor nuclei an early
      facilitation was also evoked by heteronymous low-threshold afferents. The
      heteronymous facilitation was considered to be mediated through a monosynaptic
      pathway when the difference between the central latencies of heteronymous and
      homonymous peaks was not more than 0.2 ms. The heteronymous Ia connections were
      widely distributed. In particular, monosynaptic coupling between muscles
      operating at different joints appears to be the rule in humans, though it is rare
      between ankle and knee muscles in the cat and the baboon.

PMID- 8299755
TI  - Isozyme variability of Trypanosoma brucei s.l.: genetic, taxonomic, and
      epidemiological significance.
AB  - Seventy-eight Trypanosoma brucei s.l. stocks from different hosts, representing
      the three Trypanosoma brucei subspecies and three Trypanosoma evansi stocks, were
      studied for variation at 18 polymorphic isozyme loci. The results were used to
      determine the genetic variability among stocks and to estimate gene flow among
      populations. Total genetic variability in T. brucei s.l. was less than that in
      Trypanosoma cruzi, the agent of Chagas' disease. Results support a clonal
      population structure in T. brucei, but do not preclude a hypothesis of occasional
      mating. However, some natural clones of T. brucei s.l. appear as genetically
      stable and should be considered as useful taxonomic units in applied studies.
      Greater genotypic diversity was observed in trypanosomes isolated from wild
      mammals. Numerical taxonomy methods identified a group of clones representing
      most of the human stocks from Central and West Africa. This group probably
      corresponds to Trypanosoma brucei gambiense "group I" (Gibson, Parasitology Today
      2, 255-257, 1986). As reported elsewhere, genetic evidence of the subspecies
      Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense was ambiguous,
      suggesting that these taxa represent more "nosodemes" rather than actual genetic
      clades.

PMID- 8299756
TI  - Plasmodium falciparum: further characterization of putative cation ATPases.

PMID- 8299757
TI  - Plasmodium berghei: serum-mediated inhibition of infectivity of infected mice to
      Anopheles stephensi mosquitoes.
AB  - The transmission of Plasmodium berghei-infected mice to Anopheles stephensi
      mosquitoes showed a peak number of oocysts early in the infection prior to the
      peak of gametocytaemia. This was followed by a precipitous decline on Days 4 and
      5 (see also Dearsley et al., Parasitology, 100, 359-368, 1990). By measuring
      percentage relative infectivity (using membrane feeds with viable gametocytes),
      we have shown that serum collected daily during the course of a blood-induced
      infection blocked infectivity from Day 6 postinfection onward. Although there was
      a correlation between anti-blood stage antibody levels and the loss of
      infectivity, a comparison of the infectivity pattern of P. berghei-infected
      BALB/c and SCID mice (the latter being incapable of antibody production) revealed
      the same pattern of inhibition in both mouse strains, suggesting that antibody
      alone is not responsible for this suppression. Sera taken from SCID mice late in
      the infection tested in vitro demonstrated a decline in infectivity similar to
      that observed in vivo, suggesting that a non-antibody serum factor(s) is
      responsible for the sustained decline in infectivity of P. berghei to A.
      stephensi mosquitoes.

PMID- 8299758
TI  - Cloning and characterization of ribosomal RNA genes from three species of
      Haemonchus (Nematoda: Trichostrongyloidea) and identification of PCR primers for
      rapid differentiation.
AB  - Genomic DNAs prepared from adult worms of Haemonchus contortus, Haemonchus
      placei, and Haemonchus similis were used to clone and map complete ribosomal RNA
      gene repeats from each species. The lengths of the repeating units were estimated
      at 7.2, 7.2, and 7.4 kb, respectively, with a second and distinct repeat 6.9 kb
      in length identified from H. contortus only. Restriction enzyme recognition sites
      within all ribosomal RNA genes were fully conserved except for the loss of a SalI
      site within the large subunit rRNA gene of the 6.9-kb H. contortus repeat where
      only minor differences were observed in the restriction enzyme recognition
      sequences within the external spacer DNAs. Sequence analysis of the subcloned
      small subunit ribosomal DNAs from each species demonstrated 100% conservation
      within the 1758-bp fragments with only limited sequence variability observed
      within the adjacent 5' external-transcribed spacer. Enzymatic amplification of
      external spacer sequences using primers complementary and proximal to the 3'-end
      of the large subunit and the 5'-end of the small subunit rDNAs enabled rapid
      differentiation of individual worms of H. contortus from H. placei by utilizing
      the size variability within this region of the repeat.

PMID- 8299759
TI  - Sarcoptes scabiei: the circulating antibody response and induced immunity to
      scabies.
AB  - Scabies is an important parasitic disease that continues to persist throughout
      the world despite the availability of acaricides to control it. The immune
      response mechanism to scabies and the possible development of a vaccine for
      control of scabies was investigated. This study demonstrated that hosts infested
      with scabies develop immunity (resistance) to reinfestation. All hosts developed
      scabies-specific elevated circulating antibody titers during scabies infestations
      that followed the classical pattern for primary and secondary infestations.
      Parallel elevated levels of complement C3 were also observed. The hosts that
      exhibited acquired immunity after their first infestations had antibody and
      complement levels during challenge infestations lower than those of the hosts
      that showed no immunity when reinfested. Induction of immunity coupled with
      generally elevated antibody levels for both immune and nonimmune hosts suggested
      that resistance to reinfestation was associated with a cell-mediated response.
      These data also suggested that vaccination with specific scabies tissue
      containing the relevant antigens or recombinant relevant antigens could enhance
      the cell-mediated response to protect the hosts against natural infestations.

PMID- 8299760
TI  - Sarcoptes scabiei: histopathological changes associated with acquisition and
      expression of host immunity to scabies.
AB  - The sequential changes in the histology in scabietic lesions were investigated
      for hosts (rabbits) during sensitization and reinfestation with Sarcoptes
      scabiei. Experimentally infested naive hosts developed heavy scabies infestations
      but 65% of the hosts showed induced immunity (resistance) to reinfestation. All
      hosts (naive, immune, and susceptible) exhibited an initial cell infiltrate in
      scabietic lesions that consisted predominantly of neutrophils and a few
      macrophages. This was followed by a dense plasma cell infiltrate. Upon
      reinfestation the progression of neutrophil infiltration was faster and the
      response was greater in hosts who acquired immunity than those in the susceptible
      hosts.

PMID- 8299761
TI  - Toxocara canis: failure to find IgE receptors (Fc epsilon R) on eosinophils from
      infected mice suggests that murine eosinophils do not kill helminth larvae by an
      IgE-dependent mechanism.
AB  - Eosinophils obtained by bronchoalveolar lavage (BAL) from the lungs of mice
      infected with Toxocara canis were characterized by flow cytometry with respect to
      cytophilic antibodies and surface Fc receptors. Freshly harvested BAL eosinophils
      were negative for sIgM, sIgA, sIgE, and Fc epsilon RII. These eosinophils were
      positive for sIgG1 and Fc gamma RII, although not all Fc gamma RIIs contained
      bound ligand. Culturing eosinophils for 24 or 48 hr with exogenous IgE and/or IL
      4 did not induce IgE binding capacity or Fc epsilon RII expression. IL-4 did not
      decrease Fc gamma RII expression but did decrease ligand binding capacity by Fc
      gamma RII. These findings are in marked contrast to the results of studies
      characterizing the surface of both human and rat eosinophils and may indicate
      different functional activities for mouse BAL eosinophils in helminth infections.

PMID- 8299763
TI  - Complementation of an Escherichia coli glycolysis mutant by Giardia lamblia
      triosephosphate isomerase.
AB  - The Giardia lamblia triosephosphate isomerase (TIM) gene was cloned using a probe
      generated by a polymerase chain reaction that employed primers complementary to
      highly conserved regions of TIM. The nucleotide sequence predicts a protein that
      is 38 and 47% identical to TIM from prokaryotic and eukaryotic sources,
      respectively. Like all other Giardia protein-coding genes studied thus far, the
      TIM gene lacks introns and is transcribed to yield a polyadenylated mRNA with an
      extremely short 5' untranslated region. The Giardia TIM gene complemented an
      Escherichia coli triosephosphate isomerase deletion mutant. The simplicity and
      success of complementation suggests its general utility in cloning Giardia genes
      of known function.

PMID- 8299762
TI  - Dirofilaria immitis: heartworm products contract rat trachea in vitro.
AB  - Subtle decreases in racing performance have been noted in asymptomatic greyhounds
      with heartworm burdens insufficient to obstruct pulmonary outflow, suggesting
      that alternative mechanisms may be involved in the pathogenesis of canine
      heartworm disease. Endothelium-dependent relaxation is depressed in the in vivo
      femoral artery of heartworm-infected dogs, in the in vitro pulmonary artery from
      heartworm-infected dogs, and in the in vitro rat aorta exposed to heartworms,
      heartworm-conditioned medium, and serum from heartworm-infected dogs. These
      findings suggest that circulating filarial factors may play a role in the
      pathogenesis of heartworm infection. We examined the effect of Dirofilaria
      immitis, the canine heartworm, on acetylcholine-induced contraction of rat
      tracheal rings. In epithelium-intact rings, both heartworms and heartworm
      conditioned medium increased acetylcholine-induced contraction. Pretreatment of
      the parasites with aspirin prevented the filarial-induced increase in
      acetylcholine-induced contraction, suggesting that parasite cyclooxygenase
      products are responsible for the effect. In addition, heartworms caused
      contraction in both epithelium-intact and denuded rings and this effect was
      markedly decreased by pretreatment of the worms with aspirin. Filarial
      cyclooxygenase metabolites may cause airway hyperreactivity and parasite-derived
      factors could play a role in the subtle changes in exercise performance seen in
      asymptomatic greyhounds with low worm burdens. Comparable mechanisms may be
      operating in other filarial diseases, including those that affect humans in
      tropical countries.

PMID- 8299764
TI  - Ostertagia, Haemonchus, Cooperia, and Oesophagostomum: construction and
      characterization of genus-specific DNA probes to differentiate important
      parasites of cattle.
AB  - Partial genomic DNA libraries for four common cattle parasites, Ostertagia
      ostertagi (Oo), Haemonchus placei (Hp), Cooperia oncophora (Co), and
      Oesophagostomum radiatum (Or), were generated and differentially screened with
      radiolabeled homologous and heterologous genomic DNA. Clones were identified from
      each parasite species which did not cross react with DNA from the heterologous
      genera by Southern blot or slot-blot analyses. Four clones, pOo2, pHp2.1, pCo2,
      and pOr14 were chosen for further examination. Genomic DNA from other species
      within the genera were screened with the cloned segments, and the clones were
      shown to be genus specific. The cloned fragments ranged in size from 195 to 669
      base pairs and were approximately 50% in AT content. The cloned segments, pOo2
      and pCo2, were approximately equally represented within their parasite genomes at
      0.40 and 0.62%, respectively, whereas pHp2.1 and pOr14 were significantly higher
      at 1.61 and 3.39%, respectively. Sequence analysis demonstrated that pOr14
      contained three 180-base pair tandemly repeated units with minor sequence
      variability between the repeats. Results presented here suggest that these
      sequences can detect as few as 25 eggs, and hence, may be used as diagnostic
      probes for the antemortem differentiation of trichostrongyle infections in
      cattle.

PMID- 8299765
TI  - The biology of macrophages: II. Inflammation and tumors.

PMID- 8299766
TI  - Drug-induced neutropenia due to direct effects on CFU-C--ten years of culture
      experience.
AB  - Seventeen patients with suspected drug-induced neutropenia were referred to our
      laboratory for investigation within a 10-year period. In each case, the suspected
      drugs were incorporated separately into in vitro cultures of the patients' bone
      marrow. The cultures were performed in triplicate, using multiple controls. In 10
      of these patients a drug-induced inhibition of CFU-C was demonstrated in vitro.
      The in vitro culture technique is a valuable investigation in patients with
      suspected drug-induced neutropenia, as it can help identify the causative agent,
      especially in cases of multidrug administration. It also has a useful application
      in allowing the clinician to predict drugs to which a patient may be unduly
      sensitive, and prescribe accordingly.

PMID- 8299767
TI  - Reactive oxygen species of neutrophils from patients with monosomy 7 in the bone
      marrow: contradictory chemiluminescence activity by whole blood or by purified
      cells.
AB  - Monosomy 7, a deletion of the long arm of chromosome 7, was shown in the
      neutrophils of peripheral blood in 5 of 6 patients with a myelodysplastic
      syndrome or leukemia who had monosomy 7 in their bone marrow cells. In a
      chemiluminescence assay the production of reactive oxygen species by neutrophils
      from patients was increased in whole blood and decreased in purified cells, which
      suggests that neutrophils with monosomy 7 tolerate poorly the cell purification
      procedures used. The in vitro migration of purified neutrophils obtained from
      patients with monosomy 7 was impaired. It is known that patients with monosomy 7
      have an increased susceptibility to infections. It is possible that neutrophils
      with monosomy 7 are too easily triggered to a full-scale respiratory burst and
      thereby the cells exhaust their ability to eliminate invading microbes
      efficiently.

PMID- 8299768
TI  - Determinants of red blood cell deformability in relation to cell age.
AB  - Red blood cell (RBC) deformability was determined with an ektacytometer in
      fractions separated on the basis of differences in cell volume or density.
      Deformability was measured with ektacytometry (rpm-scan and osmo-scan). We
      studied three groups of RBC fractions:1. By counterflow centrifugation we
      obtained fractions of different cell age which showed a slight decrease in mean
      corpuscular haemoglobin concentration (MCHC) and an increase in surface-to-volume
      (S/V) ratio in fractions with older cells. 2. By Percoll fractionation fractions
      were obtained which showed a pronounced increase in (MCHC) but no change in S/V
      ratio. 3. By a combination of both fractionation techniques, fractions were
      obtained which showed an increased MCHC and an increase in S/V ratio.
      Deformability in group 1,2 and 3 showed respectively no change, a moderate
      decrease and a pronounced decrease in fractions of older cells. A decline in
      deformability occurs during the aging process of the red blood cell. This decline
      in deformability in old red cells is greater than originally thought. This
      decline is the result of an increase in haemoglobin concentration and a second
      factor, probably a decrease in membrane elasticity.

PMID- 8299769
TI  - Intravascular haemolysis and increased prevalence of myeloma and monoclonal
      gammopathy in congenital dyserythropoietic anaemia, type III.
AB  - A family with congenital dyserythropoietic anaemia type III was studied. Twenty
      patients and 10 of their healthy siblings were clinically examined and questioned
      about their medical history. Blood sampling and bone marrow aspirations were also
      performed. Forty-five percent of the patients reported symptoms of anaemia and
      35% regularly felt weakness, fatigue, or headache. However, the majority of the
      patients regarded themselves as healthy. The bone marrow showed a uniform picture
      of erythroid hyperplasia with multinuclear erythroblasts and gigantoblasts with
      up to 12 nuclei. There was laboratory evidence of intravascular haemolysis and
      mild anaemia. We also observed a high prevalence of monoclonal gammopathy of
      undetermined significance (3 cases) and myeloma (1 case) among the patients.

PMID- 8299770
TI  - Induction of apoptosis in childhood acute leukemia by chemotherapeutic agents:
      failure to detect evidence of apoptosis in vivo.
AB  - This study is designed to investigate whether apoptosis occurs in vivo in
      pediatric patients with acute leukemia during induction therapy. When patients
      with common acute lymphoblastic leukemia (cALL) and acute myeloblastic leukemia
      (AML) were treated with prednisolone (60 mg/m2/day, p.o. or i.v.) and etoposide
      (150 mg/m2/day, i.v.), respectively, the blast cell counts fell to below 30% and
      5%, respectively, in 1 week. However, during this cytoreduction phase, neither
      morphologically apoptotic cells nor fragmentation of DNA derived from peripheral
      blast cells were detected at any preparations. On the other hand, cALL but not
      AML cells spontaneously undergo apoptosis following their culture in vitro. The
      addition of autologous serum instead of fetal calf serum substantially prevented
      apoptosis from occurring spontaneously in cALL cells. When cALL and AML cells
      freshly obtained from patients before therapy were treated in vitro with 10
      mumol/l prednisolone and 20 micrograms/ml etoposide, respectively, these cells
      underwent apoptosis within 6 hours, as determined by a morphological and DNA
      fragmentation assay. These in vivo and in vitro findings suggest that, although
      anticancer drugs may induce apoptosis in vivo, these apoptotic cells cannot be
      detected due to their rapid removal from the circulation.

PMID- 8299771
TI  - Serum transferrin receptor levels in anaemia of rheumatoid arthritis and effects
      of iron chelation treatment.

PMID- 8299772
TI  - Successful treatment of essential thrombocythemia with alpha interferon during
      pregnancy.

PMID- 8299773
TI  - Contemporary adhesion prevention.
AB  - OBJECTIVE: To (1) review the events leading to peritoneal adhesion formation; (2)
      review traditional adhesion prevention adjuvants; (3) overview studies for
      adhesion prevention barriers including a perspective for their use; and (4) look
      toward the future of adhesion prevention. RESULTS: A great deal of effort has
      been dedicated to reduce adhesion formation because of the morbidity associated
      with adhesions and the associated economic burden, which considering only
      hospital costs and surgeons' fees, was $1,180 million in the United States. To
      understand the role of adhesion barriers in gynecological surgery, an
      appreciation of the cellular cascade and temporal nature of peritoneal repair is
      necessary. Evidence indicates that areas denuded of peritoneum will heal
      satisfactorily and that suturing of the peritoneum may increase adhesion
      formation. Physical barriers, including both mechanical and viscous solutions,
      are widely used to prevent adhesion formation by limiting tissue apposition
      during the critical stages of mesothelial repair. Clinical studies do not support
      the use of intraperitoneal, dextran for adhesion prevention. Theoretical
      considerations of peritoneal fluid dynamics indicate that crystalloid instillates
      should not prevent adhesion formation because of their short intraperitoneal
      residence. This prediction is consistent with clinical observation. The
      availability of Interceed (Johnson and Johnson Medical, Inc., Arlington, TX) and
      Gore-Tex Surgical Membrane (W.L. Gore, Flagstaff, Arizona) barriers provides
      substantial progress in postsurgical adhesion prevention. CONCLUSIONS: Although
      many investigators are incorporating adhesion prevention barriers into their
      routine clinical situations, physician acceptance is constrained by technical
      difficulties.

PMID- 8299774
TI  - Ethical advice in reproductive medicine.

PMID- 8299775
TI  - Ovarian cancer and pregnancy: comment on a paper by Whittemore et al.
AB  - We must concede that we were not able, with the published aggregate figures, to
      correct for the nuisance variables mentioned in the report, nor were we able to
      examine the individual "Study" results to derive estimates of "Between Study"
      variation, and so assess the regularity and statistical importance of the
      patterns observed. The tentative inferences outlined in this note are made
      therefore on the assumption that the analysis of these aggregate figures provides
      a fair reflection of the complete data base. Certainly, our analyses are
      numerically consistent with those in the report by Whittemore et al. (1). Because
      of the inconsistencies discovered between portions of the data presented by
      Whittemore et al. (1), we believe that the nature of the association between
      ovarian cancer and certain features such as nulliparity and age at first
      pregnancy remains unclear and demands further investigation, possibly with the
      very data base used by Whittemore and her colleagues.

PMID- 8299776
TI  - Transcervical fallopian tube catheterization and recanalization for proximal
      tubal obstruction.
AB  - OBJECTIVE: To evaluate further the safety and efficacy of selective ostial
      salpingography combined with transcervical wire recanalization for the diagnosis
      and treatment of proximal tubal obstruction. DESIGN: Prospective study. SETTING:
      Division of Reproductive Endocrinology and Department of Radiology at Harbor
      University of California Los Angeles (UCLA) Medical Center, a tertiary care
      academic institution. PATIENTS: Twenty-eight infertile patients diagnosed with
      proximal tubal obstruction by hysterosalpingogram (HSG) or by chromopertubation
      at laparoscopy (total of 46 obstructed tubes). INTERVENTIONS: After antibiotic
      prophylaxis and IV analgesia a conventional HSG was performed. If proximal tubal
      obstruction was confirmed, selective salpingography was done under fluoroscopic
      guidance. If proximal tubal obstruction was still present, wire recanalization
      using a new prototype cannula was then performed. If recanalization was
      successful, contrast media was injected to confirm tubal patency. MAIN OUTCOME
      MEASURES: Proximal tubal patency, complete tubal patency, pregnancies. RESULTS:
      Eleven of 46 tubes (23.9%) were patent by HSG. Ostial salpingography of the
      remaining 35 tubes revealed 6 patent tubes (13%). Nine of the 29 obstructed tubes
      (31%) had successful wire recanalization, and 8 of these were patent distally.
      There were 4 intrauterine pregnancies (IUPs) and 1 ectopic pregnancy after
      recanalization and 2 IUPs after ostial salpingography. CONCLUSION: Selective
      salpingography should be considered at the time of an HSG showing proximal tubal
      obstruction. If indicated, wire recanalization can also be attempted. Selective
      ostial salpingography combined with wire recanalization is a safe and effective
      procedure for the diagnosis and treatment of PTO.

PMID- 8299777
TI  - Ultrasonographic findings of pregnancy losses after treatment for recurrent
      pregnancy loss: intravenous immunoglobulin versus placebo.
AB  - OBJECTIVE: To describe the ultrasonographic findings of pregnancies that
      terminated in repeat abortion in women participating in an ongoing randomized
      placebo-controlled clinical trial evaluating the efficacy of intravenous (IV)
      immunoglobulin (Ig) in the treatment of recurrent spontaneous abortion (SA).
      DESIGN: A prospective descriptive study of ultrasonographic findings of
      pregnancies from 27 women experiencing repeated recurrent SAs after entry into a
      clinical trial. SETTING: Clinical practice at the Genetics & IVF Institute in
      Fairfax, Virginia. PATIENTS: Women experiencing two or more consecutive recurrent
      SAs received either 500 mg/kg per mo IV Ig or placebo (albumin). To date 90 women
      have been enrolled in the clinical trial and 52 have achieved pregnancy. The
      outcome of the 52 pregnancies include 16 deliveries, 9 ongoing pregnancies, and
      27 losses. INTERVENTIONS: Ultrasonographic examinations performed in 27 women
      experiencing pregnancy loss are the subject of this study. MAIN OUTCOME MEASURES:
      The frequency of ultrasonographic findings of empty gestation sac (blighted ovum)
      and intrauterine fetal demise (IUFD) is compared between patients receiving IV Ig
      and placebo. RESULTS: Ultrasonographic findings of the 27 pregnancies losses
      included 11 blighted ova and 16 IUFDs. Of 11 blighted ova, 8 (73%) were in women
      receiving IV Ig and 3 (27%) were receiving placebo. Sixteen IUFDs were observed:
      3 (19%) in women receiving IV Ig and 13 (81%) in women receiving placebo. Of 11
      pregnancy losses occurring in women receiving IV Ig, 8 (73%) were blighted ova, 3
      (27%) were IUFDs. Sixteen pregnancy losses occurred in women receiving placebo: 3
      (19%) were blighted ova and 13 (81%) were IUFDs. The differences in frequency of
      blighted ova between IV Ig- and placebo-treated women was significant.
      CONCLUSION: IV Ig is not effective in preventing blighted ova and may be
      effective in preventing IUFDs.

PMID- 8299778
TI  - The use of a shared donor oocyte program to evaluate the effect of uterine
      senescence.
AB  - OBJECTIVE: To determine if there is reduced uterine receptivity after age 40 by
      the comparison of pregnancy rates (PRs) of donor oocyte recipients > or = 40
      years to those under age 40. SETTING: In vitro fertilization-ET facility of a
      university-based practice, Cooper Institute for In Vitro Fertilization. PATIENTS:
      All patients registering for the shared donor oocyte program from November 1990
      to September 1992. Most recipients were in ovarian failure. INTERVENTIONS: Donors
      were treated with luteal phase leuprolide acetate (LA) and gonadotropins;
      recipients were treated with oral E2 in graduated doses and 50 mg IM daily P.
      Endometrial thickness was considered in the decision to continue with transfer or
      to freeze all embryos. MAIN OUTCOME MEASURES: Pregnancy rates per transfer in
      recipients and live birth rates according to age > or = 40 or < 40. RESULTS: The
      clinical PR per transfer was 29.2% for the younger women and 25.4% for the older
      recipients. The live birth rate was 29.2% for the younger women and 22.4% for the
      older recipients. CONCLUSIONS: These data support the conclusion that, if there
      is a decline in uterine receptivity for embryo implantation with advancing age,
      it is at least remediable with hormonal adjustments.

PMID- 8299779
TI  - Comparison of the cumulative probability of pregnancy after in vitro
      fertilization-embryo transfer by infertility factor and age.
AB  - OBJECTIVE: To compare the cumulative probability of pregnancy after multiple IVF
      cycles by age and cause of infertility. DESIGN: A prospective study was done in
      which patients were followed from the time they registered for their first IVF
      cycle until they achieved a clinical pregnancy, withdrew from treatment, or study
      was terminated. PATIENTS, SETTING, TREATMENTS: Infertile women undergoing IVF-ET
      at the Cooper Institute for In Vitro Fertilization were enrolled in this study if
      the luteal phase leuprolide acetate (LA) and hMG controlled ovarian
      hyperstimulation (COH) regimen was used. MAIN OUTCOME MEASURES: Clinical
      pregnancy, as determined by a positive beta-hCG level and ultrasonographic
      confirmation of a gestational sac, and delivery rates based on number of women
      with live births were compared by infertility factor and age. RESULTS: The 3
      month cumulative probability of pregnancy based on life table analysis was 33% in
      women with tubal factor who were < or = 35 years of age, 25% in women with tubal
      factor who were > 35 years of age, 30% for women with multiple factors who were <
      or = 35 years of age, and 14% for women with multiple factors who were > 35 years
      of age. The rate for the older women with multiple factors was significantly
      lower than that for the other groups. The delivery rates were lower for the women
      with multiple factors than for women under 35 with tubal factor only.
      CONCLUSIONS: There is a significant effect of age and infertility factor on
      pregnancy and delivery rates. Physicians should consider these factors in
      evaluating their patients' prospects for success in IVF-ET.

PMID- 8299780
TI  - Pregnancy rates in donors versus recipients according to the serum progesterone
      level at the time of human chorionic gonadotropin in a shared oocyte program.
AB  - Previous data suggested a subtle increase in serum P at the time of hCG injection
      without LH surge reduces the PR of women having oocyte retrievals for IVF; this
      study compared PRs of recipients in a shared oocyte program according to the
      donors' pre-hCG P level. There was no difference in viable PRs between recipients
      and donors when P < or = 1 ng/mL. The PR was similar for recipients when donors'
      P was > 1 ng/mL (12.7%). Donors with P > 1 ng/mL had the lowest PR: 7.2%. The
      data suggest that the adverse effect of higher serum P without LH surge may be on
      the endometrium rather than the oocyte.

PMID- 8299781
TI  - Correlation between epididymal length and fertilization rate in men with
      congenital absence of the vas deferens.
AB  - OBJECTIVE: To investigate whether the variable length of the epididymides in men
      with congenital absence of the vas deferens might have a correlation with IVF and
      pregnancy rate results. DESIGN: Microsurgical retrieval of epididymal sperm from
      men with congenital absence of the vas deferens and their use for IVF. SETTING:
      Center for Reproductive Health, University of California, Irvine, California.
      PATIENTS: One hundred eight men with confirmed diagnosis of congenital absence of
      the vas deferens enrolled in the microsurgical epididymal sperm aspiration and
      IVF program. INTERVENTIONS: Measurement in centimeters of the epididymal length
      at the time of the sperm aspiration procedure. MAIN OUTCOME MEASURE: Rates of
      fertilization and pregnancy according to the epididymal length. RESULTS: Three
      groups were identified: group I (n = 29), epididymal length between 0.5 and 1.9
      cm; group II (n = 66), length between 2.0 and 4.0 cm; and group III (n = 13),
      length in excess of 4.0 cm. Although the aspiration site was the proximal caput
      for each case, patients of group III had the highest fertilization and pregnancy
      rate (24% and 43%, respectively). Patients with the shortest epididymis (group I)
      had the worst IVF outcome (fertilization rate 7% and pregnancy rate 7%) whereas
      in group II the fertilization rate was 13% and the pregnancy rate was 18%.
      CONCLUSION: This study demonstrates that epididymal sperm from men with
      congenital absence of the vas deferens having a longer epididymis have a better
      IVF rate. A long epididymis can allow [1] the arrival of more frequent waves of
      fresh sperm whereas in a short epididymis the system is completely congested and
      occupied by old and senescent sperm, [2] less obstructive damages, and [3] a back
      flow of biochemical factors produced in the more distal segments that could
      ultimately enhance the fertilization capacity of proximal epididymal sperm.

PMID- 8299782
TI  - Semen preparation with the Sperm Select System versus a washing technique.
AB  - OBJECTIVE: To compare sperm migration through sodium hyaluronate with simple
      washing as methods for preparing sperm for IUI. DESIGN: Ten normal semen
      specimens were prospectively collected and samples were prepared by simple
      washing and by migration into sodium hyaluronate using the Sperm Select System
      (Select Medical Systems, Williston, VT). The semen and each treatment group were
      evaluated for sperm concentration, percent motile, viability, acrosomal status,
      longevity, and computer-aided semen analysis (CASA) parameters. SETTING:
      University reproductive endocrinology facility. RESULTS: The recovery of motile
      sperm was significantly higher for the washing method (mean +/- SEM 75% +/- 7%)
      than for the hyaluronate method (10% +/- 1%). The number of motile sperm
      recovered by migration into hyaluronate was independent of the percentage of
      motile sperm in the semen specimen and positively correlated with sperm
      concentration. The hyaluronate method produced greater percentages of motile,
      viable, and morphologically normal sperm, with lower proportions of premature
      acrosome reactions, higher sperm velocity, and greater linearity. CONCLUSIONS:
      The Sperm Select System method of sperm separation provides a highly uniform
      specimen with improved sperm quality. However, the recovery of motile sperm is
      considerably lower than for simple washing methods.

PMID- 8299783
TI  - Comparison of flutamide and spironolactone in the treatment of hirsutism: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare the clinical efficacy and safety of the pure antiandrogen
      flutamide and the steroidal derivative spironolactone in the treatment of
      hirsutism in women. DESIGN: Fifty-three premenopausal women suffering from
      moderate to severe hirsutism were randomized into two groups and received either
      flutamide or spironolactone in association with a triphasic oral contraceptive
      (OC) pill. Hirsutism, acne, seborrhea, alopecia, and side effects were monitored
      monthly for a treatment period of 9 months and a follow-up after treatment period
      of 6 months. Blood samples were taken at each visit for assessment of endocrine,
      biochemical, and hematologic parameters. RESULTS: After only 6 months of therapy,
      flutamide caused a maximal reduction in the hirsutism score to a value within
      almost normal range; during the same period, spironolactone caused only a 30%
      reduction of the hirsutism score. Whereas flutamide caused a dramatic (80%)
      decrease in total acne, seborrhea, and hair loss score after only 3 months of
      therapy, spironolactone caused only a 50% reduction in acne and seborrhea, with
      no significant effect on the hair loss score. Four patients in the spironolactone
      group but only one in the flutamide group stopped the medication because of
      adverse side effects. CONCLUSION: The present data obtained in a randomized
      prospective study clearly demonstrate that the pure antiandrogen flutamide is
      superior to spironolactone in the treatment of female hirsutism and its related
      androgen-dependent symptoms and signs in women.

PMID- 8299784
TI  - Detection of a unique 32-kd protein in the peritoneal fluid of women with
      endometriosis.
AB  - OBJECTIVE: To test the hypothesis that endometriotic tissue secretes
      endometriotic-specific proteins into the peritoneal fluid (PF) of women with
      endometriosis. DESIGN: A prospective design was utilized in this study. SETTING:
      Tertiary care, university-based center and reproductive endocrinology laboratory.
      PARTICIPANTS: Women of reproductive age who were infertile with endometriosis (n
      = 19), as well as without endometriosis (n = 7), and fertile women undergoing
      tubal ligation (n = 6). INTERVENTIONS: Collection of PF fluid via laparoscopy.
      MAIN OUTCOME MEASURES: Peritoneal fluid proteins were isolated and assessed by
      two-dimensional polyacrylamide gel electrophoresis. RESULTS: Two-dimensional
      electrophoresis of PF proteins isolated a group of proteins (M(r) = 32 to 40 kd,
      pI = 4.5 to 5.2) in all PF samples that was similar to the rat endometriotic
      implant-specific protein, Endo-1. This group of proteins consisted of 5 to 12
      individual proteins with endometriosis PF containing a significantly higher
      number of proteins (median = 11) compared with either PF from infertile women
      without endometriosis (median = 8) or from women undergoing tubal ligation
      (median = 7). In addition, one protein (M(r) = 32 kd, pI = 5.8), termed EPF-32,
      was detected predominantly (18 of 19 samples analyzed) in PF from women with
      endometriosis. This protein was also detected in PF from infertile women without
      endometriosis (2 of 7 samples) but not in the PF of fertile women undergoing
      tubal ligation (0 of 6 samples). The appearance of this protein was not
      associated with the severity of endometriosis. CONCLUSION: It is concluded from
      this study that PF from women with endometriosis predominantly contains a 32-kd
      protein (EPF-32) compared with the PF of women without the disease. The role of
      EPF-32 in the pathophysiology of endometriosis is not established but this
      protein may function as a diagnostic marker for endometriosis.

PMID- 8299785
TI  - Altered interleukin-6 production by peritoneal leukocytes from patients with
      endometriosis.
AB  - OBJECTIVES: To investigate the ability of peritoneal leukocytes to produce
      interleukin-6 (IL-6) in vitro and to determine whether IL-6 is present in the
      peritoneal fluid (PF) in vivo. DESIGN: Peritoneal leukocytes were assessed for
      spontaneous versus stimulated IL-6 production. Interleukin-6 in the PF was also
      quantitated. SETTING: Leukocytes were recovered from PF obtained at the time of
      diagnostic laparoscopy for pain and infertility or from women undergoing
      bilateral tubal ligation. PATIENTS: The study population included a total of 24
      women. Experimental groups consisted of women undergoing tubal ligations (n = 6),
      patients with postinflammatory pelvic adhesions unrelated to endometriosis (n =
      6), and women with minimal to mild endometriosis (n = 6), or moderate to severe
      disease (n = 6). RESULTS: Peritoneal leukocytes from normal control women and
      patients with severe endometriosis spontaneously produced low levels of IL-6. In
      contrast, cells from women with mild disease or adhesions spontaneously released
      twofold to fourfold higher levels of this cytokine. Peritoneal leukocytes from
      patients with both mild and severe endometriosis were refractory to additional
      cytokine release directly in response to stimulation with endotoxin. Bioactive IL
      6 was present in the PF of all patient groups, whereas immunoreactive IL-6 was
      not detected in this fluid. CONCLUSIONS: These data demonstrate that IL-6 was
      present in the PF of all patient groups. However, the ability of peritoneal
      leukocytes to produce IL-6 in vitro differed according to stage of disease. We
      hypothesize that altered leukocyte IL-6 production in vivo may contribute to the
      pathophysiology of endometriosis.

PMID- 8299786
TI  - Comparison of the impact of oral versus transdermal estrogen on serum
      lipoproteins.
AB  - In an attempt to compare the effects of transdermal and oral conjugated estrogen
      on serum lipoproteins, 35 premenopausal women who underwent total abdominal
      hysterectomy and bilateral salpingo-oophorectomy were randomized to receive
      either 0.625 mg of conjugated oral estrogen or 0.05 mg transdermal 17 beta-E2
      during the first postoperative year. Lipid profiles were assessed before surgery
      and at 3, 6, 9, and 12 months of therapy in each subject. Neither oral nor
      transdermal estrogen replacement therapy produced significant changes on serum
      lipoproteins at the end of first year when compared with baseline preoperative
      values. We conclude that both transdermal and oral administration of estrogen are
      promising in the maintenance of premenopausal lipid values after menopause.

PMID- 8299787
TI  - Does increasing frequency of intrauterine insemination improve pregnancy rates
      significantly during superovulation cycles?
AB  - OBJECTIVE: To compare pregnancy rates (PR) per treatment cycle of controlled
      ovarian hyperstimulation (COH) patients receiving a single IUI with COH patients
      receiving two IUIs. DESIGN: A prospective randomized trial of consecutively
      treated patients attending our infertility clinic for COH and IUI. METHODS:
      Patients undergoing COH by hMG and hCG were randomized to receive either one
      (group A) or two (group B) IUIs. Randomization was performed using a random
      number table. Group A IUIs were timed 35 hours after ovulatory hCG, whereas group
      B IUIs were performed 19 and 43 hours after hCG. RESULTS: A total of 120 patients
      during 169 cycles were randomized between group A (90 cycles) and group B (79
      cycles). Data analysis demonstrated no significant differences between groups A
      and B with respect to age, indications for COH, duration of hMG treatment, total
      amount of hMG administered, peak E2 levels, number of dominant follicles
      recruited, or mean number of total motile sperm inseminated. Pregnancy rates for
      groups A and B were 0.11 and 0.14, respectively. The size of our study population
      permits a conclusion that a 300%, 200%, or 100% difference in PR between the two
      groups does not exist (power 0.97, 0.80, or 0.61, respectively). CONCLUSION:
      Among patients undergoing COH and IUI, increasing the frequency of insemination
      does not provide a significant increase in cycle pregnancy rate.

PMID- 8299788
TI  - The more accurate timing of insemination with regard to ovulation does not create
      a significant improvement in pregnancy rates in a donor insemination program.
AB  - OBJECTIVE: To determine if the accurate prediction of ovulation before artificial
      insemination of frozen donor semen was justified by increased pregnancy rates.
      DESIGN: A retrospective study of inseminations, over a 2-year period,
      administered to women who were enrolled on a donor insemination program and who
      were monitored using one of four ovulation timing regimens. Also, a study of the
      significance of follicle status at the time of insemination with relevance to
      pregnancy was carried out. SETTING: A university teaching hospital donor
      insemination program. PATIENTS: Patients entered in this study were undergoing
      insemination with thawed, cryopreserved, donor semen. MAIN OUTCOME MEASURES:
      Pregnancy and follicle status at the time of insemination. RESULTS: There was no
      statistically significant difference in pregnancy rates between the four methods
      of ovulation detection most commonly used for artificial insemination.
      Inseminations several hours either side of ovulation did not result in a
      significantly different pregnancy rate than inseminations carried out closer to
      ovulation. CONCLUSION: More accurate and expensive methods of detecting changes
      in ovulation result in no significant increase in fecundity than other less
      expensive timing techniques.

PMID- 8299789
TI  - Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a
      prospective, randomized, crossover study during intrauterine insemination cycles.
AB  - OBJECTIVE: To test the hypothesis that in couples undergoing IUI, actively
      managed cycles using clomiphene citrate (CC) stimulation, ultrasound monitoring,
      and hCG timing will result in increased pregnancy rate (PR) per cycle compared
      with unstimulated urinary LH-timed cycles. PATIENTS: Fifty-six couples with
      unexplained infertility (n = 26) or male factor infertility (n = 30) participated
      in the study. SETTING: Tertiary academic medical center. DESIGN: Prospective,
      randomized, crossover. Couples were randomized initially to one of the two study
      groups (treatment A: LH-timed IUI; treatment B: CC-stimulated, hCG-timed IUI). If
      no pregnancy occurred, each couple alternated between the two regimens during
      subsequent cycles, up to a total of four cycles. RESULTS: Twenty-nine couples
      completed the study and the analysis of 95 cycles revealed that among the male
      factor infertility group, one pregnancy occurred during the 26 cycles of each
      treatment group (PR per cycle of 3.9% for both treatment groups). In contrast,
      among the unexplained infertility group, there was a marked difference in the
      effect of treatments. During treatment A only one pregnancy occurred in 20 cycles
      (PR of 5% per cycle) whereas during treatment B, six pregnancies occurred in 23
      cycles (PR of 26.1% per cycle). CONCLUSIONS: If IUI is chosen as the treatment
      modality in unexplained infertility, the addition of active ovulation management
      that includes CC stimulation, ultrasound monitoring of folliculogenesis, and hCG
      timing of ovulation increases the PR per cycle. In couples with male infertility,
      PR per cycle is low and is apparently not affected by the addition of active
      ovulation management.

PMID- 8299790
TI  - Intracellular pH changes during zona drilling.
AB  - OBJECTIVE: To investigate whether zona drilling of oocytes, a technique used to
      locally disrupt the zona pellucida, causes important changes in intracellular pH.
      DESIGN AND METHODS: In a first set of experiments, intracellular pH was measured
      during zona drilling of mouse oocytes, using pH-sensitive microelectrodes. In a
      second set of experiments human oocytes that failed to fertilize were used to
      measure intracellular pH during drilling. In these cells intracellular pH was
      measured using microfluorimetry with the pH-sensitive dye 2',7'-bis-carboxyethyl
      5(6)-carboxyfluorescein. RESULTS: In mouse oocytes intracellular pH dropped from
      7.25 +/- 0.02 (mean +/- SEM) to 7.09 +/- 0.03 during zona drilling, followed by a
      recovery to pH 7.17 +/- 0.02 after 4 minutes (n = 20). In human oocytes,
      intracellular pH dropped over 0.36 +/- 0.10 pH units during drilling, followed by
      a recovery that was complete within 4 minutes (n = 14). CONCLUSION: Zona drilling
      is associated with a significant cytoplasmic acidification both in mouse and
      human oocytes. This effect is perhaps related to the high incidence of
      cytoplasmic degeneration after zona drilling of human oocytes.

PMID- 8299791
TI  - Task force report on the outcome of pregnancies and children conceived by in
      vitro fertilization (France: 1987 to 1989).
AB  - OBJECTIVE: To describe the outcome of pregnancies conceived by IVF and the follow
      up of the children after a minimum of 1 year of life. DESIGN: Survey of clinical
      pregnancies and follow-up of the children and comparison with national
      statistics. SETTINGS: All clinical pregnancies from 11 French centers between
      January 1987 and June 1989. PATIENTS: A total of 1,637 pregnancies resulting in
      1,263 deliveries and 1,669 live-born or still-born children and 1,411 alive
      children after 1 year. MAIN OUTCOME MEASURES: Gestational age of birth, birth
      weight, mortality rates, prevalence of congenital malformation, and prevalence of
      disorders during the follow-up of the children. RESULTS: The preterm birth rate
      was 22.7% of all deliveries and 12.2% of single deliveries compared with 5.6% in
      France, and 34.7% of babies weighed < 2,500 g compared with 5.2% in France. The
      rate of perinatal, neonatal, and infant mortality were higher than the national
      average. The rate of malformation (2.86%) was comparable with national survey
      (2.08%). The health of children diseased during the whole follow-up was
      approximately 2%. CONCLUSION: The health of children after 1 year of live is
      close normal.

PMID- 8299792
TI  - Bromocriptine reverses the inhibitory effect of macrophages on human sperm
      motility.
AB  - OBJECTIVE: To determine the effects of PRL suppression on the activation of
      murine peritoneal macrophages and their subsequent effects on human sperm
      motility. DESIGN: Laboratory study. INTERVENTIONS: Mice were treated with
      subcutaneous implants of 2.5 mg bromocriptine pellets 7 days before bacillus of
      calmette and guerin (BCG), a strain of Mycobacterium bovis, injection for
      activation of macrophages. Bromocriptine treatment, which significantly
      suppressed circulating PRL levels, continued through the day of peritoneal
      macrophage collection. Macrophages were subsequently cultured for 4 days and
      culture supernatant was collected. MAIN OUTCOME MEASURES: Human sperm were
      incubated for 4 hours in the presence of culture medium or culture supernatant
      from control and treated mice. Motion analysis was performed at 0, 2, and 4
      hours. RESULTS: A significant decrease in human sperm motility was observed in
      the presence of culture supernatant from activated murine peritoneal macrophages.
      After 4 hours of incubation, sperm motility decreased from 69% +/- 3% in the
      nonactivated macrophage control group to 37% +/- 6% in the BCG- activated
      macrophage group. The suppressive effect of soluble products of activated
      macrophages on human sperm motility was reversed when mice were rendered
      hypoprolactinemic with bromocriptine. Motility after 4 hours was 56% +/- 3% in
      the BCG-bromocriptine group. Simultaneous administration of bromocriptine and PRL
      (100 ng per mouse daily) restored the inhibitory effect of soluble products of
      activated macrophages on sperm motility (36% +/- 5% motile). CONCLUSIONS: PRL may
      modulate the deleterious effects of activated macrophages on human sperm
      motility, thereby suggesting novel and useful methods for the modification of the
      immune response in early reproduction.

PMID- 8299793
TI  - A morphological and functional study of fusibility in round-headed spermatozoa in
      the human.
AB  - OBJECTIVE: To study the molecular origin and functionality of the plasma membrane
      of round-head spermatozoa in the human. DESIGN: Clinical and laboratory study.
      SETTING: Patients in a clinical and academic environment. PATIENTS: Men with
      round-head spermatozoa. RESULTS: Pisum sativum lectin homogeneously stains the
      surface of round sperm; however, the staining pattern and transmission electron
      microscopy show that the plasma membrane does not alter after exposure to the
      calcium ionophore A23187. In a clinical program, round-head spermatozoa injected
      subzonally into metaphase II oocytes with or without pretreatment with the
      fusogen polyethylene glycol did not bind or fuse to the oocyte surface.
      CONCLUSION: The data suggests that plasma membrane fusion in human gametes is
      regulated by specific surface molecules and that exposure of these molecules on
      the sperm surface cannot be triggered by elevating intracellular calcium alone.

PMID- 8299794
TI  - Sperm motility, morphology, hyperactivation, and ionophore-induced acrosome
      reactions after overnight incubation with mycoplasmas.
AB  - OBJECTIVE: To evaluate the effect on the function on human sperm of overnight
      incubation with mycoplasma species. DESIGN: Prospective controlled in vitro
      study. SETTING: Community-based sperm bank and andrology laboratory.
      INTERVENTIONS: Percoll-separated sperm were incubated overnight with a low
      densities of Myco-plasma hominis and Ureaplasma urealyticum serotypes. MAIN
      OUTCOME MEASURES: Motility, midpiece and tail morphology, hyperactivation after
      overnight capacitation, and acrosome status after incubation with calcium
      ionophore. RESULTS: Overnight incubation with mycoplasma species resulted in
      small but highly statistically significant differences in motility, morphology,
      hyperactivation after overnight capacitation, and proportion acrosome reacted
      after incubation with calcium ionophore compared with controls. CONCLUSIONS:
      Incubation with mycoplasma species impairs sperm physiology. Identification and
      treatment of mycoplasma may augment a physiology-based infertility evaluation.

PMID- 8299795
TI  - Defective calcium influx and acrosome reaction (spontaneous and progesterone
      induced) in spermatozoa of infertile men with severe teratozoospermia.
AB  - OBJECTIVE: To evaluate the acrosome reaction and its prerequisite, a calcium
      influx, in spermatozoa of infertile men with a high incidence of abnormal sperm
      forms. DESIGN: Prospective, controlled study. SETTING: Academic tertiary assisted
      reproduction center. PATIENTS: Patients (n = 14) were allocated in the study
      after semen evaluation showed teratozoospermia (< 14% normal sperm forms) as
      diagnosed by strict criteria. INTERVENTIONS: After swim-up separation of the
      motile fraction, acrosome reactions were evaluated using Pisum sativum agglutinin
      (both spontaneously and exogenously induced with P and the calcium ionophore
      A23187, both at 10 microM); the intracellular-free [Ca2+]i was assessed by the
      fluorescent fura-2 indicator (basal and after P). RESULTS: Patients did not show
      the typical P-induced wave of [Ca2+]i that was observed in controls but rather a
      blunted response, no response at all, or abnormal basal [Ca2+]i levels. The
      percent of basal acrosome reaction was significantly lower for patients versus
      controls postswim-up, and at 1 hour and 3 hours. Furthermore, there was a
      significant difference in the response of acrosome reaction to P both at 1 hour
      and 3 hours, with patients showing almost no response at all. However, patients'
      acrosome reaction response to the calcium ionophore was similar to those of
      fertile men. CONCLUSION: Infertile patients with a high incidence of abnormal
      sperm forms as diagnosed by strict criteria have a low incidence of spontaneous
      acrosome reaction and a diminished P-stimulated acrosome reaction, whereas the
      nonspecific response to a calcium ionophore is conserved. Parallel abnormalities
      of [Ca2+]i were observed in patients, suggesting that these sperm populations may
      have a defective nongenomic P sperm receptor and/or abnormalities of other
      membrane transduction systems.

PMID- 8299796
TI  - Correlation of semen variables and pregnancy rates for donor insemination: a 15
      year retrospective.
AB  - OBJECTIVE: To determine the validity of the criteria currently used to select
      fertile sperm donors. DESIGN: Retrospective study of the outcome of donor
      insemination treatment cycles over a 15-year period. SETTING: The Reproductive
      Medicine Clinic of Prince Henry's Institute of Medical Research (formerly Medical
      Research Centre, Prince Henry's Hospital, South Melbourne, Victoria, Australia).
      PATIENTS: Couples (1,299) presented with severe male factor infertility
      (azoospermia or severe oligozoospermia) and were treated by donor insemination
      (10,796 treatment cycles) using cryopreserved semen from 292 normal healthy men
      aged between 18 and 46 years as sperm donors. MAIN OUTCOME MEASURES: Semen
      characteristics, including volume, count, motility, motility index, normal
      morphology, live cells, and post-thaw motility, were analyzed by logistic
      regression analysis to determine which groups of factors were related
      independently and significantly to pregnancy rates. RESULTS: The pregnancy rate
      for donor insemination was 8.9% per cycle. By logistic regression count, normal
      morphology, post-thaw motility (%), and post-thaw motility index together
      explained 28% of the variance of the pregnancy rates. Other factors, including
      prethaw motility characteristics (percent motility and motility index), donor
      age, weight, LH, FSH, and T levels, were not significant. CONCLUSIONS: The
      standard parameters of sperm count, morphology, and post-thaw motility are the
      most important factors for the selection of highly fertile donors. As most of the
      variability in the pregnancy rates resulted from other undetermined factors
      related both to the donor and the recipient, it is suggested that the pragmatic
      approach of discarding donors after a reasonable number of treatment failures (20
      to 50) should continue.

PMID- 8299797
TI  - Human oviductal fluid prolongs sperm survival.
AB  - OBJECTIVE: To compare the effect of human oviductal fluid on sperm motility and
      hyperactivation during 9 hours' incubation in vitro with follicular fluid (FF)
      and medium controls. DESIGN: Fertile donor spermatozoa were allowed to penetrate
      human cervical mucus in vitro and then recovered and incubated in either 30%
      human oviductal fluid, 20% FF, or medium for up to 9 hours. Sperm motion
      characteristics were measured using a sperm motility analyzer. SETTING: The donor
      insemination program at the University Clinic within the Jessop Hospital for
      Women, Sheffield, United Kingdom. PATIENTS: All donors used in this study were
      involved in the donor insemination program. MAIN OUTCOME MEASURES: Sperm
      motility, hyperactivation, curvilinear velocity, progressive, lateral head
      displacement, and linearity were measured using a sperm motility analyzer.
      RESULTS: After 9 hours' incubation, spermatozoa in human oviductal fluid had a
      significantly higher percentage motility than sperm incubated in FF or the
      control medium. A more linear sperm motion was consistently observed in the
      spermatozoa incubated in human oviductal fluid: significantly different from FF
      and media at 3 hours and 6 hours. The effect of human oviductal fluid on
      maintaining sperm motility was not affected by the addition of P. CONCLUSION:
      Human oviductal fluid can maintain sperm motility in a mechanism that is not
      mediated by the low concentration of P. We suggest that human oviductal fluid is
      a favorable environment for sperm survival.

PMID- 8299798
TI  - Fine needle tissue aspiration biopsy of the testis.
AB  - OBJECTIVE: To develop a fine needle tissue aspiration biopsy technique that
      provides sufficient tissue for accurate histological assessment and research
      purposes. DESIGN: After assessing different needles and developing a method for
      handling small amounts of tissue, 87 patients underwent fine needle tissue
      aspiration biopsy. The quantity, quality, and appearance of the tissue was
      examined and adverse effects of the procedure were noted. Fine needle tissue
      aspiration and open biopsy samples were compared in 26 patients. Suitability of
      the tissue for flow cytometry and electron microscopy was also assessed. RESULTS:
      The 20-gauge, 5-cm Menghini and Turner biopsy needles penetrated the testis more
      readily and recovered larger quantities of tissue. Adequate samples were
      recovered from 83% of cases (average of 21.8 tubule sections per testis) with the
      frequency of recovery and the amount of tissue obtained increasing through-out
      the study. Some distortions of the tissue were seen but these rarely interfered
      with the diagnosis. Although many patients suffered slight discomfort during the
      injection of the anesthetic, no serious complications were encountered during or
      after the procedure. Comparison of fine needle tissue aspiration and open biopsy
      diagnoses found either full agreement (56%) or slight differences (38%) in the
      degree of hypospermatogenesis. CONCLUSIONS: Fine needle tissue aspiration biopsy
      was found to be a quick, easy, repeatable, and reproducible method of obtaining
      testicular tissue. No serious adverse effects of the procedure were detected and
      the diagnoses were found to be comparable to those obtained by open biopsy.

PMID- 8299800
TI  - Adnexal torsion: color Doppler diagnosis and laparoscopic treatment.
AB  - The present case documents normalization of ovarian perfusion after conservative
      laparoscopic treatment of adnexal torsion. At our institution, Doppler flow
      assessment in cases of suspected torsion represents an important element of
      diagnosis and, in this case, allowed for early diagnosis with conservative
      laparoscopic treatment with documented normalization of ovarian flow
      postoperatively.

PMID- 8299799
TI  - Nicotinamide, a component of complex culture media, inhibits mouse embryo
      development in vitro and reduces subsequent developmental potential after
      transfer.
AB  - OBJECTIVE: To determine the effects of B-group vitamins present in culture media
      on mouse embryo development in vitro and subsequent viability. DESIGN: Mouse
      zygotes were cultured in the presence of B-group vitamins. Embryo morphology and
      cell numbers were determined at 96 and 120 hours after hCG. Viability was
      assessed by transfer of embryos after 3 days of culture to pseudopregnant
      recipients. Resultant pregnancy rates (PRs) and fetal weights were determined.
      RESULTS: Supplementation of an amino acid-free medium with minimal essential
      medium (MEM) B-group vitamins significantly decreased embryo cleavage rates,
      whereas the inclusion of Ham's F-10 medium B-group vitamins significantly reduced
      both cleavage rates and morphological development. Subsequent experiments
      determined that nicotinamide (5 microM) significantly reduced blastocyst cell
      number, implantation rate, viable PR, and fetal weight. CONCLUSION: The data
      indicate that nicotinamide inhibits mouse embryo development in culture and
      reduces viability. Nicotinamide is present at high levels in Ham's F-10 and MEM
      media that are used routinely in human embryo culture. The role of vitamins in
      human embryo development in vitro warrants investigation.

PMID- 8299801
TI  - Tubal selection for gamete intrafallopian transfer.
AB  - When both fallopian tubes appear normal, tubal selection for GIFT is left to the
      surgeon's discretion. We were interested to learn whether pregnancy rates were
      influenced by the choice of tubal transfer in relation to ovarian dominance.
      Ovarian dominance was defined sonographically as the ovary containing the greater
      number of follicles having a mean diameter > 16 mm. In a retrospective analysis
      of 144 GIFT procedures, the clinical pregnancy rate for transfers performed to
      the tube ipsilateral to the dominant ovary was significantly higher than that of
      transfers made to the contralateral tube (0.414 versus 0.228, P = 0.042). This
      difference could not be attributed to either patient characteristics or cycle
      performance. We suggest that gamete transfer be performed ipsilateral to the side
      with the greater number of dominant follicles to optimize pregnancy rates.

PMID- 8299802
TI  - Optic neuropathy associated with clomiphene citrate therapy.
AB  - A 31-year-old woman developed acute visual loss in her right eye immediately
      after a 5-day course of CC for primary infertility. Although she gradually
      recovered vision, she did not return to 20/20 acuity in that eye. As CC may cause
      vascular sludging, it is hypothesized that increased blood viscosity resulted in
      sufficiently reduced flow in a posterior ciliary artery to produce an anterior
      ischemic optic neuropathy. Patients experiencing visual symptoms while taking
      clomiphene should have their eyes examined promptly for evidence of visual
      changes or optic nerve injury.

PMID- 8299803
TI  - Preservation of fertility despite subnormal gonadotropin and testosterone levels
      after cessation of pulsatile gonadotropin-releasing hormone therapy in a man with
      Kallmann's syndrome.
AB  - A man with IHH and anosmia presented in 1980. He was successfully treated with
      various hormonal regimens; four children were conceived with hCG or pulsatile
      GnRH therapy. The patient discontinued GnRH after the fourth child was conceived,
      and testosterone enanthate injections were prescribed. However, he took the
      injections only briefly and 15 months later he demonstrated continuing
      spermatogenesis despite low serum FSH and LH levels. His wife successfully became
      pregnant. This case adds to the recognized range of recovery in IHH, with
      fertility despite stopping hormonal therapy and despite low serum gonadotropin
      and T levels.

PMID- 8299804
TI  - Kallmann syndrome and associated malformation of the uterus.
AB  - Kallmann syndrome is a rare combination of hypogonadotropic hypogonadism due to
      hypothalamic insufficiency and anosmia. In both patients treated at our
      institution for infertility, a malformation of the uterus was noted: one patient
      had a unicornuate uterus, the other a uterus with a fundal hypoplasia and tubes
      of approximately 9 cm. It is not clear if the malformation is in association with
      Kallmann syndrome or purely coincidental. Given the known association of other
      malformations with Kallmann syndrome, we suppose that probably an underlying
      genetic defect having to do with organogenesis is the cause of the uterine
      malformations.

PMID- 8299805
TI  - Intrauterine insemination in fertile women delivers larger number of sperm to the
      peritoneal fluid than intracervical insemination.
AB  - Randomized IUI or intracervical insemination of eight fertile women with 50 x
      10(6) sperm was performed to determine whether IUI delivers more spermatozoa to
      the peritoneal cavity. After IUI (n = 4), 2,053 to 29,450 sperm were recovered in
      the PF at laparoscopy. No sperm were found in the PF after intracervical
      insemination (n = 4). After IUI, CM contained 1.0 x 10(6) to 57.0 x 10(6)
      sperm/mL; after intracervical insemination, 0 to 1.2 x 10(3) sperm/mL were seen.
      One therapeutic mechanism for IUI is delivery of larger sperm numbers to the
      fertilization site by rapid (4 hours) transport. In addition, there is greater
      retrograde colonization of CM that may result in sustained release of sperm.

PMID- 8299806
TI  - The "red queen" and endometrial hyperplasia.

PMID- 8299807
TI  - Peritoneal fluid and endometriosis.

PMID- 8299808
TI  - Fine needle testicular biopsy--one or more punctures?

PMID- 8299809
TI  - Pros and cons of "add-back" therapy.

PMID- 8299810
TI  - [Langerhans cell histiocytosis].
AB  - The authors describe a case of a 4 years old boy. In connection with this case
      they discuss the latest classification of histiocytosis accepted by the
      Histiocytosis Society, and the stomatological aspects of the disease (severe
      gingivitis, necrosis of the gingivae, ulceration, and high degree of tooth
      mobility). The new classes of the disease: Langerhans cell's histiocytosis, Non
      Langerhans cell's histiocytosis, malignant histiocytosis.

PMID- 8299811
TI  - [Microbiology of root surface caries].
AB  - There are no significant differences between the microflora of root surface
      caries and enamel caries. However, intact root surfaces and active lesions may
      show differences in the proportion of microorganisms. S. mutants together with
      Lactobacillus on the same surface indicate a higher risk for root surface caries.

PMID- 8299812
TI  - [Prosthetic classification of dental implants].
AB  - The author's suggestion is a new implantological prosthetical classification
      according to the number and position of the remaining teeth. It is simple, taking
      into consideration the procedure of becoming edentulous, showing the grade of
      difficulty of the implantological application and gives advices for making the
      treatment plan.

PMID- 8299813
TI  - [Epidemiologic study of mid-face fractures in a 14-year (1977-1990) material of
      the authors' clinic].
AB  - The authors made a retrospective study of fractures of the maxilla analyzing the
      occurrence, localisation and the causal factors of the injury. The treated 223
      patients with fracture of the middle face during this period. The most exposed
      age group was the group of 21-40 years, the most frequent causes were: traffic
      accident, brawl, and sport accident. The proportion of fracture of middle face
      and mandible was 1:2. As to the localisation of the fractures, the simple
      fracture in the lateral area was the most frequent.

PMID- 8299815
TI  - [Honorary lecturers in dentistry (1848-1951)].
AB  - On the Faculty of Medicine of Pest, respectively Budapest University, were 29
      honorary lecturer dentists between 1848 and 1951. On the Faculties of Medicine of
      Universities of Kolozsvar, Szeged, Debrecen and Pecs there were 8 honorary
      lecturer dentists. In 1951 the communist regime abolished the institution of
      honorary lecturer and forbade honorary lecturers from using their titles. The
      paper lists the data of Hungarian honorary lecturer dentists.

PMID- 8299814
TI  - [Comparison of the cleansing effect of two micromotor-driven endodontic hand
      pieces. I. Comparison ot the cleansing effect of the two handpieces].
AB  - The aim of the study was to assess the cleansing-effect of two endodontic
      handpieces (Excalibur, W & H; MM 1400 Micro Mega) in root canals that were
      previously manually prepared, and treated with chlor-(Neomagnol) and citric acid
      containing solutions. The analyses were performed by scanning electron microscope
      (SEM). The elimination of the Smear Layer (SL) with Neomagnol was not successful
      with either of the two handpieces. The cleansing of the Superficial Debris (SD)
      with Neomagnol activated by MM 1400 was significantly more effective in the
      apical (p < 0.05) and in the middle (p < 0.01) third of the root-canal, than by
      Excalibur. In contrast, SL was better eliminated by Excalibur using citric acid,
      significant differences--when compared with MM 1400--could be seen in the middle
      third (p < 0.05) of the root-canal. The handpieces seem to have their own
      specific characteristics: thus MM 1400 was better in eliminating the SD (used
      with Neomagnol), while Excalibur was superior in eliminating the SL (used with
      citric acid).

PMID- 8299816
TI  - Knowing your colleagues can improve health care.

PMID- 8299817
TI  - Quality management in the correctional health care system.

PMID- 8299818
TI  - AIDS impact series helps meet the federally mandated OSHA training.

PMID- 8299819
TI  - Just another day.

PMID- 8299820
TI  - Challenges of a correctional nurse.

PMID- 8299822
TI  - Florida's intervention project for nurses expands to assist HIV infected nurses.

PMID- 8299821
TI  - County jail health care services: summary of findings.

PMID- 8299823
TI  - State of the society.

PMID- 8299824
TI  - A clustering of childhood meningococcal disease: a challenge for physicians,
      press and community.

PMID- 8299825
TI  - The more significant and lasting work of the Board of Medical Practice (BMP).

PMID- 8299826
TI  - Actionable medical ethics: informed consent (Part II--Research subjects).

PMID- 8299827
TI  - More on the National Practitioner Data Bank.

PMID- 8299828
TI  - Ultrasonography in the investigation of salivary gland disease.

PMID- 8299829
TI  - An evaluation of the Sens-A-Ray digital dental imaging system.
AB  - The Sens-A-Ray digital imaging system was compared with group D- and E-speed
      intraoral radiographic film with respect to resolution, speed and image quality.
      Using a line-pair plate, resolution was determined to be 10 line-pairs per
      millimetre. With a constant potential X-ray source, the speed of the system was
      over three times that of E-speed emulsion and the response of pixel value to
      exposure was linear. Absorption curves with aluminium showed a similar response
      to D-speed film. An aluminium foil test object was used to compare the Sens-A-Ray
      system with both film types. Thirty observers were scored for successful
      identification of a pattern of holes in the test object. There was little
      difference between D- and E-speed film groups, and successful identification was
      significantly reduced with the Sens-A-Ray images when compared with D- and E
      speed films.

PMID- 8299830
TI  - Exposure reduction in cephalography with a digital photostimulable phosphor
      imaging system.
AB  - The effect on the determination of the cephalometric landmarks of exposure
      reduction using computed radiography with a photostimulable storage phosphor was
      evaluated. Forty patients attending for regular review were divided into four
      groups of 10. The first group was exposed to the same amount of radiation as that
      required for a conventional calcium tungstate screen-film combination. The other
      three groups were exposed to approximately 50, 20 and 10% respectively of the
      radiation dose of the first group. Ten dentists determined the landmarks. The
      coordinates of the points were recorded to measure the consistency of landmark
      identification. It was found that in comparison with the conventional screen-film
      system, a substantial reduction of exposure could be achieved with computed
      radiography for cephalography without clinical detriment.

PMID- 8299831
TI  - Perception of image quality in direct digital radiography after application of
      various image treatment filters for detectability of dental disease.
AB  - This study evaluated dentists' perception of the quality of digitally captured
      radiographs. Thirty radiographs were taken with the Visualix digital video
      radiographic system, 10 periapicals for tooth and bone anatomy, 10 periapicals
      for bone disease and 10 bitewings for dental caries. Three numeric copies were
      made of each image and treated with three different filters: 'optimize',
      'enhance' and 'enhance + smooth', respectively. Four images of the same case were
      displayed simultaneously in a random sequence on the monitor. Twenty dentists
      ranked each set of four images on a scale from 1 to 4. In general, most dentists
      preferred a treated image to the original. The optimized and enhanced images were
      selected most frequently as first or second choice from the tooth and bone
      anatomy and bone disease groups. The original image was ranked lowest in more
      than half (55%) of the series. For the bitewings, the smoothed images were ranked
      significantly higher. In conclusion, image treatment possibilities should be
      offered in digital radiography as the majority of dentists preferred a treated
      image to the original version. The image treatment chosen seemed to be task
      dependent; less treatment was required to delineate the more subtle tissue
      differences.

PMID- 8299832
TI  - Blind chance? An investigation into the perceived probabilities of phrases used
      in oral radiology for expressing chance.
AB  - The necessity for numerical probabilities in oral radiographic diagnosis is
      increasing, due to recent developments in computer-aided diagnosis, decision
      analysis, informed consent and medical litigation. These numerical probabilities
      are only partly available from current texts on oral radiology, where they are
      often expressed by ill-defined, semiquantitative phrases. Therefore, in this
      study 30 phrases expressing the probability of a relationship between a diagnosis
      and its symptoms were taken from a selected textbook on oral radiology. Seven
      oral radiologists from the USA and the Netherlands scored each of these
      probabilistic phrases on a 20-cm visual analogue scale. Low intraradiologist and
      high interradiologist variation was found. Because the high variation among
      authors of texts on oral radiology in interpreting probability information could
      have a negative influence on their ability to transfer unambiguous information to
      their readers, it is recommended that the use of semiquantitative phrases in oral
      radiology is restricted to five probability groups.

PMID- 8299833
TI  - Taurodontism in a young adult Chinese population.
AB  - The first and second molars on the panoramic radiographs of 196 consecutive 15-19
      year-old Chinese adults (male:female ratio; 46:54) were assessed in order to
      establish the prevalence of taurodontism, which is considered to be a marker of
      underlying genetic disease. The criteria of Shifman and Chanannel (Community Dent
      Oral Epidemiol 1978; 6: 200-3) were employed and the measurements made digitally.
      Taurodontism was present in 46.4% of patients in this series with a greater
      prevalence in females (56% compared to 36% in males, P < 0.001). It was found in
      21.7% of all teeth examined, and the prevalence was significantly greater in
      females (26% for compared with 17.4% in males, P < 0.001). Our results suggest
      that taurodontism is not sufficiently sensitive to be a marker of genetic disease
      in Chinese.

PMID- 8299834
TI  - Use of 'rapid' processing techniques by a sample of British dentists.
AB  - Knowledge of current practices amongst general dental practitioners (GDPs) is
      important in planning postgraduate and undergraduate teaching curricula and in
      ensuring the relevance of clinical research. A number of methods are available to
      dentists for the rapid production of intraoral radiographic images, including
      concentrated and monobath chemistry. No current data exists about the use of such
      'rapid' systems in the UK. The aim of this study was to obtain this data,
      including the relative popularity of the different systems. A questionnaire on
      'rapid' processing of radiographs was distributed to all 855 GDPs in four Family
      Health Services Authorities in North West England. Responses were received from
      326 GDPs (38.1%). 29.4% of GDPs used some kind of 'rapid' system, with 'packet
      processed' films being the most popular. 6.1% of all GDPs used 'rapid' systems
      routinely, while the remainder used them for specific situations, typically
      emergencies and endodontics.

PMID- 8299835
TI  - Diagnosis of coronoid process hyperplasia by three-dimensional computed
      tomographic imaging.
AB  - Three-dimensional (3D) CT imaging was performed on three cases (one unilateral,
      two bilateral) of coronoid process hyperplasia. This technique displayed the
      impingement of the enlarged coronoid process on an exostosis on the lower border
      of the malar bone. In addition, a small concavity was found on the inner surface
      of the malar bone that was not displayed by other imaging modalities. The 3D
      images were useful in planning surgical treatment. In cases of limitation of
      opening, finding a malar exostosis on conventional radiographs such as a Water's
      view should suggest the presence of coronoid process hyperplasia even if the
      impingement cannot be demonstrated.

PMID- 8299836
TI  - Adenocarcinoma: the use of computed tomography and magnetic resonance imaging for
      investigation of a tumour in the infratemporal fossa.
AB  - A case of a salivary gland adenocarcinoma involving the right infratemporal fossa
      is presented. The diagnostic and clinical management of the case was aided by the
      use of both CT and MRI.

PMID- 8299837
TI  - Sialectasis and HIV infection.
AB  - The sialographic findings of the parotid gland of an HIV-positive patient are
      presented. Multiple areas of sialectasia were noted and their similarity to
      Sjogren's syndrome is discussed.

PMID- 8299838
TI  - Teaching veneer and crown margins in UK dental schools.

PMID- 8299839
TI  - The limitation of visual perception in restorative dentistry.
AB  - Accurate judgement of size, depth and angle is required in the practice of
      restorative dentistry. Most assessments are made simply by visual examination,
      and these judgements are therefore often subjective; the limitation of visual
      perception renders such judgements inaccurate and subject to variation. The use
      of standardized objects to allow size or angle judgement by direct comparison
      improves accuracy, and their routine use may improve the quality of restorative
      treatment.

PMID- 8299840
TI  - Oral surgery for children: 2. Anaesthesia and sedation.

PMID- 8299841
TI  - Development of the integrated general practitioner training scheme in
      orthodontics.
AB  - A training scheme for general dental practitioners (GDPs), based on that
      recommended by the British Orthodontic Standards Working Party, has been set up
      within Northern Ireland. It has been developed to encourage and support
      interested GDPs to diagnose and treat suitable patients orthodontically within
      their own practice, to widen the scope of their orthodontic expertise and to
      increase experience through clinical attachments to consultant units, backed up
      by theoretical and practical sessions. The aim of the scheme was to heighten
      interest, identify suitable patients and to increase the accuracy of referral for
      advice and treatment elsewhere. It is hoped that this framework may be of
      interest and value to those in other centres, who may be considering ways and
      means of making orthodontic treatment more available. By following this pattern,
      it is hoped that in due course, this integrated approach of clinical attachment
      and theoretical module may progress towards the setting up of a national network,
      adequately funded by the Department of Health.

PMID- 8299842
TI  - Beware the missing denture: it could be hidden within.

PMID- 8299843
TI  - A case of fractured genial tubercles.

PMID- 8299844
TI  - Computerized design of removable partial dentures: a knowledge-based system for
      the future.
AB  - Dentists frequently fail to provide dental technicians with the design
      information necessary for the construction of removable partial dentures. The
      computerization of dental practices and the development of appropriate knowledge
      based systems could provide a powerful tool for improving this aspect of dental
      care. This article describes one such system currently under development which is
      an example of the kind of additional facility that will become available for
      those practices with the necessary hardware.

PMID- 8299845
TI  - Heterotopic heart transplants in Biomphalaria glabrata (Mollusca: Pulmonata).
      Fate of congeneric xenografts.
AB  - Hearts were implanted heterotopically into the hemocoel of NIH albino
      Biomphalaria glabrata from three xenogeneic donor snails, including two New World
      (B. obstructa, B. tenagophila) and one Old World (B. alexandrina) species, as
      well as from wild type allogeneic donors. Recipients were examined histologically
      at 1, 3, 7, 10, 15, 30, 60, 120, and 180 days postimplantation (PI). Grafts from
      all four donor species were temporarily infiltrated by recipient hemocytes at
      early intervals PI and in most instances also became encapsulated. Furthermore,
      the grafts subsequently showed histopathological alterations and abnormal
      heartbeat relative to preimplantation controls. However, hemocytic reactions
      eventually subsided, the implants remained structurally intact, and implant
      myocardial cells both maintained high levels of intracellular glycogen and
      continued to contract rhythmically for 6 months. No major differences occurred in
      fates among different xenografts, or between xenografts and allografts. Our
      observations of prolonged xenograft survival differ from those of previous
      investigators, most of whom have reported rapid destruction of implanted
      xenogeneic tissues in molluscs.

PMID- 8299846
TI  - A novel adhesion protein expressed by ciliated epithelium, hemocytes, and
      leukemia cells in soft-shell clams.
AB  - The ontogeny of circulating hemocytes and tumor cells in mollusks has been
      approached using monoclonal antibodies to normal cells. A monoclonal antibody,
      previously shown to identify an adhesion related protein (p130), has been used to
      define the reactivity of cells in tissues from normal soft-shell clams (Mya
      arenaria) and soft-shell clams with leukemia. Using immunoperoxidase technology,
      we have determined that hemocytes, connective tissue cells, and a subset of
      leukemia cells that are adherent share a cross-reactive epitope with cilia.

PMID- 8299847
TI  - Phagocytosis associated chemiluminescence of hemocytes in Mytilus edulis
      (Bivalvia).
AB  - The respiratory burst associated with phagocytosis by Mytilus edulis hemocytes
      was investigated by measurement of luminol-dependent chemiluminescence (LDCL).
      After experimental parameters (number of cells, quantity of stimulus) were
      determined, the biochemical mechanisms involved in the chemiluminescent process
      were investigated using inhibitors of oxygen radicals and enzymes. In particular,
      catechol-like phenols suggested the involvement of NADPH-oxidase and peroxidase
      in oxidative metabolism of mussel hemocytes. The variability of LDCL response
      observed among individuals and separated hemocyte subpopulations strongly
      suggests a variable immunocapacity depending on hemogram composition. Using a
      specific monoclonal antibody to discriminate different hemocyte types, the
      eosinophilic granulocytes appeared to exhibit the highest LDCL activity.

PMID- 8299848
TI  - Intracellular signaling in arthropod blood cells: involvement of protein kinase C
      and protein tyrosine phosphorylation in the response to the 76-kDa protein or the
      beta-1,3-glucan-binding protein in crayfish.
AB  - Degranulation (regulated exocytosis) of crayfish granular blood cells and release
      of the prophenoloxidase activating system can be triggered by two endogenous
      ligands, a 76-kDa cell adhesion protein or a beta-1,3-glucan-binding protein when
      reacted with beta-1,3-glucan (beta GBP-L). These ligands bind a recently
      described membrane receptor. Degranulation triggered by these ligands was
      inhibited by the protein kinase C (pkC) inhibitor staurosporine or by the
      tyrosine kinase inhibitor herbimycin A. Incubation with the 76-kDa protein
      increased tyrosine phosphorylation of a granular cell protein of approximately 80
      kDa. In addition, the pkC activating phorbol esters PMA or beta PDD degranulated
      the cells in a dose-dependent manner, whereas the control isomeric phorbol ester
      alpha PDD that does not activate pkC did not have any effect on the cells. Thus,
      we propose that binding of the 76-kDa protein or beta GBP-L to the receptor
      triggers cellular responses via a pathway that includes pkC activation and
      protein tyrosine phosphorylation.

PMID- 8299849
TI  - Development of the lymphomyeloid system in the dogfish, Scyliorhinus canicula.
AB  - Previous studies on the morphology of the lymphomyeloid tissues in the dogfish,
      Scyliorhinus canicula, have been confined to adults. This study was restricted to
      the structure and functioning of the developing immune system in embryonic and
      post-hatch dogfish. A major feature of the developing immune system in S.
      canicula, is the succession of haemopoietic/lymphoid tissues. The liver is the
      first tissue to contain immunoglobulin positive cells at 2 months, followed by
      the interstitial kidney at 3 months. The thymus, spleen, and Leydig organ appears
      at 4 months while the epigonal and gut-associated lymphomyeloid tissues are the
      last tissues to differentiate. The haemopoietic/lymphoid nature of the kidney and
      thymus disappear at post-hatch and the other lymphomyeloid tissues persist
      through adult life. By the time of egg case splitting (ca. 6 months), when
      embryos receive massive exposure to water-borne antigens, the structural
      development of most of the lymphomyeloid tissues is well advanced.

PMID- 8299850
TI  - Characterization of serum immunoglobulins in a chondrostean fish, Acipenser
      baeri.
AB  - The euglobulin fraction of sturgeon (Acipenser baeri) serum was analyzed using
      electrophoretic and immunoblotting techniques. The major protein of this fraction
      is an IgM-like molecule composed of equimolar 70-kDa glycosylated H chains and 26
      30 kDa L chains. In the absence of a reducing agent, the L and H polypeptides may
      form (mu 2L2)n high molecular weight polymers, mu 2L2 170-kDa units or L2 dimers.
      These different bonding patterns suggest some structural heterogeneity in the
      distribution of cysteine residues along the sturgeon Ig chains. The H chain N
      terminal sequence indicates significant homologies with the conserved VHIII
      subgroup. Heavy chains antigenically different from the 70-kDa H chain were not
      detected, suggesting that IgM is the only Ig class synthesized by this sturgeon
      species.

PMID- 8299851
TI  - Studies on lymphocyte subpopulations and the effect of age on immune competence
      in turkeys.
AB  - We characterized the lymphocyte subpopulations and investigated the effect of age
      on cellular and humoral immunity, development of lymphoid organs, and the
      relative proportions of CD4+ and CD8+ cells in turkeys. The mitogenic responses
      of peripheral T cells were poorly developed at hatch but developed rapidly after
      hatch and reached adult levels by 2 weeks-of-age. The average percentage of CD4+
      cells was 45, 29.8, and 26.3 in the thymi, peripheral blood, and spleens,
      respectively, in turkeys. The mean percentage of CD8+ cells in the thymi,
      peripheral blood, and spleens of turkeys was 53.8, 13.6, and 15.5, respectively.
      Age did not influence the relative proportions of CD4+ and CD8+ T cells in the
      spleens and peripheral blood of turkeys. The mean percentages of IgM+ cells in
      the bursae and spleens were 78.5 and 26.8, respectively. Day-old turkeys did not
      develop detectable antibodies to either thymus dependent or independent antigens.
      However, 2 week or older turkeys showed good humoral responses. Inoculation of
      BSA at hatch induced tolerance, whereas injection of SRBC did not. Analysis of
      relative organ weights of turkey lymphoid organs showed that spleens and thymi
      developed rapidly during the first week-of-age.

PMID- 8299852
TI  - Immunocytochemical study of Peyer's patches follicular-associated epithelium in
      the marsupial, Didelphis albiventris.
AB  - The lack of probes defining leukocyte subpopulations has restricted ontogenetic
      studies of the opossum gut. We report for the first time the organization of the
      gut cellular immune components using species cross-reactive antibodies. Mouse
      monoclonal antibodies against human HLA-DR were used together with
      immunocytochemistry to demonstrate MHC class II-like antigens in the opossum
      Peyer's patches (PP). Positive staining was obtained in the M cell and
      enterocytes comprising the follicular-associated epithelium (FAE). Rabbit
      polyclonal antibody against human CD3 stained opossum thymocytes and T-cell
      dependent areas of spleen, lymph node, and PP interfollicular zones, but failed
      to stain intraepithelial lymphocytes in the FAE. In contrast rabbit polyclonal
      antibody against human IgA stained B-cell immunocytes and plasma cells present in
      the M-cell lateral invaginations. It is surmised that B-cell activation could
      occur in the opossum M-cell niches by thymus independent antigens, bypassing T
      helper-cell function.

PMID- 8299853
TI  - Cloning and sequence analysis of kappa and gamma cynomolgus monkey immunoglobulin
      cDNAs.
AB  - One gamma heavy chain and 10 kappa light chain cynomolgus monkey (Macaca
      fascicularis) immunoglobulin cDNAs have been cloned and sequenced. Comparisons of
      the variable (V) regions to human antibody sequences have revealed extensive
      identity, exhibiting 93% at the amino acid level for the VH framework regions,
      and 88-99% for the V kappa frameworks. Identification of very few cynomolgus
      monkey-specific framework region residues suggests a role for cynomolgus monkey
      antibodies as donators of variable regions to chimeric monoclonal antibodies for
      utilisation in human therapy with human constant (C) regions. The cynomolgus
      monkey C kappa region exhibited 83% amino acid identity to its human counterpart,
      and the C gamma region was 95, 93, 95, and 95% similar to the human C gamma 1, C
      gamma 2, C gamma 3, and C gamma 4 regions, respectively. Evolutionary analysis of
      the C gamma genes, using the silent molecular clock, suggests that the divergence
      between cynomolgus monkey and human occurred before the time at which the
      ancestral gamma gene diverged into the multiple isotypes observed in humans.

PMID- 8299854
TI  - Ketanserin alone and in combination with enalapril in the treatment of essential
      hypertension: assessment of the haemodynamic effects.
AB  - The antihypertensive and haemodynamic efficacies of ketanserin and ketanserin
      plus enalapril were compared. The monotherapy phase of the study involved the
      oral administration of 40 mg ketanserin twice daily or 20 mg enalapril once daily
      for 12 weeks to 25 hypertensive patients. Systolic and diastolic blood pressures
      were significantly reduced by both drugs. Left ventricular function both at rest
      and during effort improved significantly with either drug. This was due to a
      reduction of end-systolic volume; end-diastolic volume decreased only with the
      use of enalapril. Combination therapy, involving 16 patients and both drugs given
      at the original dosage schedule for 12 weeks, resulted in further reductions in
      systolic and diastolic blood pressures, and an improvement in left ventricular
      function; indices of diastolic function were not modified. In conclusion,
      ketanserin and enalapril showed comparable antihypertensive and haemodynamic
      activities. A combination of ketanserin and enalapril increased the favourable
      characteristics of both drugs.

PMID- 8299855
TI  - Effect of prostaglandin E1 on the renin-aldosterone system in patients with
      diabetic nephropathy.
AB  - The effect of prostaglandin E1 (PGE1) on the renin-aldosterone system was
      investigated in hospitalized patients with non-insulin-dependent diabetes
      mellitus presenting with continuous proteinuria but without nephrotic syndrome.
      Of the 20 patients studied, 10 had continuous positive proteinuria > or = 200
      mg/day and 10 had continuous positive proteinuria < 200 mg/day. Prostaglandin E1
      (40 micrograms in 100 ml normal saline) was infused intravenously over 2 h twice
      daily for 4 weeks. Plasma renin activity (PRA) and the plasma aldosterone
      concentration (PAC) were determined by radioimmunoassay at 0 and 120 min after a
      frusemide injection given before the start of PGE1 treatment and during
      administration of PGE1 in week 4. The patients who had proteinuria < 200 mg/day
      showed significant decreases in the PRA0 and the ratio of PRA120:PRA0 and a
      decrease in the PAC120 during prostaglandin PGE1 administration. When the results
      for the two patient groups were combined, both the PAC120 and the PRA120 were
      found to be significantly lowered during administration of PGE1. The results
      indicate that PGE1 may be valuable in the treatment of diabetic nephropathy,
      since the compound inhibited the increased reactivity of the renin-aldosterone
      system in patients with non-insulin-dependent diabetes mellitus.

PMID- 8299856
TI  - Effect of high ethanol intake on vascular reactivity to serotonin, vasopressin
      and acetylcholine in normotensive rats.
AB  - Chronic ethanol administration causes hypertension and alterations of vascular
      reactivity in rats. In several models of hypertension, alterations of vascular
      reactivity are believed to be secondary to the sustained increase in blood
      pressure. The present study investigated the effects of serotonin (5
      hydroxytryptamine [5-HT]), vasopressin and acetylcholine (ACh) in the isolated
      perfused mesenteric arteries from Wistar rats submitted to an 8-week course of
      chronic ethanol intake (8 g/kg.day). No significant differences were observed in
      the dose-response curves with regard to: pressor effect of 0.04-10.0 nmole 5-HT;
      relaxant effect of 0.05-50.0 nmole ACh; or the pressor effects of two 1.5-nmole
      doses of vasopressin between control rats and ethanol-fed rats. These results
      suggest that modifications in arterial reactivity to endogenous vasoactive
      substances (observed in other studies involving more prolonged ethanol treatment
      in rats) may be, in part, secondary to the increase in blood pressure.

PMID- 8299857
TI  - The effect of mesoglycan in patients with cerebrovascular disease: a psychometric
      evaluation.
AB  - Mesoglycan is a preparation of natural glycosaminoglycans, containing mainly
      heparan sulphate and dermatan sulphate. A clinical trial was conducted to
      evaluate the efficacy and the tolerability of once-daily mesoglycan in 30
      patients with clinical evidence of cerebrovascular insufficiency. Clinical
      effectiveness was assessed using psychometric and neurological scales: Sandoz
      Clinical Assessment for Geriatric Patients (SCAG); Parkside Behaviour Rating
      Scale Modified; Geriatric Depression Scale; and Anxiety Evaluation. Mesoglycan
      was given as a single oral once-daily dose of 100 mg for a period of 6 months.
      This treatment was shown to have positive effects on the cognitive and
      behavioural parameters evaluated. The effects on SCAG were already evident after
      3 months' treatment and a significant improvement was observed after 6 months in
      those patients with a moderate to severe disease. During the treatment period
      only one patient suffered an adverse reaction attributed to the drug
      investigated.

PMID- 8299858
TI  - Liver pathology in cytomegalovirus infection associated with hepatitis B virus.
AB  - A retrospective study was carried out in 56 patients to establish the association
      of cytomegalovirus (CMV) with active or inactive hepatitis B virus (HBV)
      infection as a possible risk factor in the development of severe liver disease.
      Patients with positive CMV serology and active or inactive HBV infection had
      elevated alanine aminotransferase activity and had a relatively high incidence of
      more severe lesions (chronic hepatitis and active cirrhosis). In the absence of
      CMV, only one case of cirrhosis was identified compared with seven cases of
      hepatic fibrosis. By analogy with hepatitis C virus, CMV may bring about
      activation of the host inflammatory response against hepatocytes following HBV
      infection, resulting in the development of severe hepatitic disease.

PMID- 8299859
TI  - Circadian variation in the onset of acute myocardial infarction: lack of an
      effect due to age and sex.
AB  - The circadian patterns in the onset of symptoms of acute myocardial infarction
      were assessed in a prospective study involving 450 patients. Analysis of the data
      in the 424 patients in whom the time of onset was known did not show any
      statistically significant circadian rhythms, either for the group as a whole or
      for subgroups divided according to sex, age group (< 60, 60-69, 70-79 and > or =
      80 years old), or the presence or absence of diabetes mellitus. The frequency of
      onset of symptoms was highest in the morning (06.01-12.00 h) for the group as a
      whole (29.2%). Patients aged < 70 and > or = 80 years old showed a peak in the
      morning, whereas patients aged 70-79 years old showed a peak in the afternoon
      (12.01-18.00 h).

PMID- 8299860
TI  - Use of prostaglandin E1 to treat peri-anaesthetic pulmonary hypertension
      associated with mitral valve disease.
AB  - Severe pulmonary hypertension (PH) can be a critical problem during and after
      cardiac surgery, since it increases right ventricular afterload resulting in
      decreased cardiac output. A case of pulmonary hypertension associated with mitral
      valve disease and resistant to glyceryl trinitrate therapy during surgery is
      reported. The case was treated successfully with prostaglandin E1 (PGE1),
      indicating that PGE1 can be used peri-operatively in a patient with refractory PH
      resistant to glyceryl trinitrate treatment.

PMID- 8299861
TI  - True linear polymerization shrinkage of unfilled resins and composites determined
      with a linometer.
AB  - A device, which was given the name "linometer", has been developed for measuring
      linear polymerization shrinkage of both unfilled resins and composites. The
      results were in agreement with those obtained with the mercury dilatometer. The
      present method is simple, fast, insensitive to temperature fluctuations, is
      operational at any temperature and, if desired, samples can be maintained in a
      100% relative humidity environment. The linometer offers an easy means for
      routine polymerization shrinkage determinations and therefore may be useful in
      evaluating new monomer systems for dental composites. The linear polymerization
      shrinkage for several unfilled resins and composites was measured with this
      device.

PMID- 8299862
TI  - Mold filling and porosity in castings of titanium.
AB  - The present study focused on the effects of argon pressure, mold venting, and
      investment permeability on the mold filling of titanium and the soundness of
      titanium castings. Casting soundness was determined by density measurement and x
      ray radiography. To achieve complete filling of molds made from a relatively
      impermeable investment, the molds were vented. Regardless of the presence or
      absence of vents, all of the molds made from a highly permeable refractory
      material filled completely. The soundness of castings made under an argon
      pressure of 50 torr was significantly greater than that of castings made under a
      pressure of 400 torr. The non-vented molds of the highly permeable refractory
      material yielded the soundest castings (mean density = 4.45 g/cm3).

PMID- 8299863
TI  - Bond strengths to superficial, intermediate and deep dentin in vivo with four
      dentin bonding systems.
AB  - The shear bond strength of four dentin bonding systems which remove or modify the
      smear layer were measured in vivo in dog canine and molar teeth as a function of
      dentin depth. Dentin bond strengths were higher with cuspid teeth compared to
      molar teeth. Most bonding systems gave higher bonds to superficial dentin and
      progressively lower bond strengths deeper dentin. The highest bond strengths were
      obtained with Clearfil Liner Bond, followed by Superbond C&B, Scotchbond 2 and
      Tenure. The former two bonding systems achieved shear bond strengths to cuspids
      that were > 10 MPa regardless of dentin depth while the latter two systems
      produced bond strengths < 10 MPa. In molars, the same ranking of bonding systems
      was noted but the value that separated the high from the low bonds was 5 MPa.

PMID- 8299864
TI  - Setting stresses in composites for two different curing modes.
AB  - As a continuation of a study into the development of the polymerization shrinkage
      stress of chemically initiated composites (CC), the development of the
      polymerization shrinkage stress of light-initiated composites (LC) in relation to
      the configuration-factor was determined. During setting, the LC composites
      generated a higher polymerization shrinkage stress, developed higher cohesive
      strength to resist this stress and showed less flow than their CC analogues.
      Trying to find a comprehensive explanation for the differences in behavior of
      stress development in LC and CC composites, the effect of mixing-in of porosity
      was also investigated on LC composites. Mixing-in of porosity slowed down and
      decreased the shrinkage stress development. This was attributed to either oxygen
      inhibition due to admixed air or to an increase of free surface from the presence
      of pores within the bulk of the composite.

PMID- 8299865
TI  - Derangement of composite filler distribution inside syringe-type delivery
      systems.
AB  - Used and almost emptied syringes of two brands of composites contained material
      close to the pestle-head that appeared to be more granular and dry, as compared
      to the composite obtained from unused syringes. The present results suggest that
      a derangement of filler and matrix phases occurred inside the used syringes when
      compared to unused controls. Stress imposed on the composite material inside the
      unused syringes resulted in a comparable derangement of filler and matrix phases.
      Although this derangement was limited, the effect could contribute to intra- and
      interlaboratory scattering of data.

PMID- 8299866
TI  - Tensile fatigue of two composite cements bonding three base metal alloys to
      bovine enamel.
AB  - Tensile fatigue endurance limits were determined for three base metals (Ni-Cr, Ni
      Cr-Be, and Co-Cr) bonded to bovine enamel using two composite cements: a Bis
      GMA/phosphate ester composite cement which relies on a sand-blasted metal
      surface, and a Bis-GMA composite luting cement which relies on electrolytically
      etched metal surfaces. Samples were tested to failure or to 10(6) cycles at 5 hz
      in Ringer's solution at 37 degrees C, and endurance limits were determined using
      a two-point test strategy. SEM evaluation was performed on fractured samples to
      determine failure mode. Statistical analysis of the results showed no difference
      between cements when using Ni-Cr-Be; however when using Co-Cr, the Bis
      GMA/phosphate ester cement produced greater values than the Bis-GMA cement that
      relied on electrolytical etching. The opposite result occurred when a Ni-Cr alloy
      was tested with both cements. Evaluation of the results for each cement with the
      three different alloys showed statistical significant differences. SEM fracture
      analysis revealed a mixed failure pattern with apparent adhesive fracture from
      both the composite-enamel and composite-metal interfaces and cohesive failure
      throughout the cement.

PMID- 8299867
TI  - Fluoridated carbonatoapatite in the intermediate layer between glass ionomer and
      dentin.
AB  - The intermediate layer between a glass ionomer restoration and dentin was
      examined morphologically by scanning electron microscopy (SEM) and Fourier
      transform infrared spectroscopy (FTIR). SEM showed strong bonding between the
      dentin and glass ionomer and formation of an intermediate layer between them.
      FTIR spectra of successive scrapings through the ionomer/dentin interface zone
      showed that the intermediate layer is composed primarily of mineral fluoridated
      carbonatoapatite. The presence of this sparingly soluble mineral at the interface
      between the tooth and the restoration may provide high resistance to secondary
      caries and may, thus, be of great clinical importance.

PMID- 8299868
TI  - The effect of repeated stretching on the force decay and compliance of vulcanized
      cis-polyisoprene orthodontic elastics.
AB  - Compliance measurements, used in the past to measure the viscoelastic properties
      of dental impression materials, were used to assess these properties in
      vulcanized cis-polyisoprene orthodontic elastics, and the results were compared
      with traditional force decay measurements. Both methods were also used to
      evaluate the effect of repeated stretching on these elastics. Compliance
      measurements successfully characterized the viscoelastic behavior of the
      elastics, and the results agreed with force decay measurements. Repeated
      stretching significantly reduced the force and the compliance of the elastics.
      There was no statistical difference in the force or compliance measurements after
      the elastics were stretched more than 200 times. Stretching for 1000 cycles of
      400% extension reduced elastic force by approximately 12%.

PMID- 8299869
TI  - Polymeric calcium phosphate cements: analysis of reaction products and
      properties.
AB  - Chemical and mechanical properties of water-based polymeric calcium phosphate
      cements (PCPC) were investigated. These cements were derived from mixing several
      types of water-soluble polymers, e.g., gelatin, poly(vinyl alcohol) (PVA), and
      poly(alkenoic acids) such as poly(acrylic acid), with a calcium phosphate cement
      (CPC) mixture consisting of equimolar amounts of tetracalcium phosphate (TTCP)
      and anhydrous dicalcium phosphate (DCPA) as well as several other TTCP-containing
      mixtures. Cement formation was observed with all of the PCPCs. With the gelatin
      and PVA cements, significant amounts of hydroxyapatite (HA) formation were
      observed within 24 h. Their setting times and mechanical properties were similar
      to those of the purely inorganic CPC that is derived from the reaction of TTCP
      and DCPA in water. Although the mechanical properties of a gelatin-CPC cement
      were only slightly improved, its handling characteristics were superior to that
      of CPC. Significantly faster setting and stronger cements were obtained using
      polycarboxylic acid polymers with CPC. However, only small amounts of HA were
      observed in these types of polymeric cements even after 1 mon storage in
      distilled water at 37 degrees C. This research demonstrates the feasibility of
      preparing several new types of dental cements based on the interaction of water
      soluble polymers with a self-setting calcium phosphate powder mixture.

PMID- 8299870
TI  - Polymeric calcium phosphate cements: setting reaction modifiers.
AB  - In this study, the effects of several additives on the setting behavior and
      mechanical properties of polymeric calcium phosphate cements were investigated.
      The cements were derived from a polycarboxylic acid (PCA) and a calcium phosphate
      cement (CPC) powder that consisted of equimolar amounts of tetracalcium phosphate
      (TTCP) and dicalcium phosphate (DCPA). Retardation of the setting reaction in the
      PCA-CPC cements was observed by adding tribasic sodium phosphate and fluorides
      such as stannous fluoride, zirconium(IV) fluoride and titanium(IV) fluoride. It
      was found that increasing the concentration of these additives decreased the
      mechanical strength of the cements. However, improvements in both setting and
      mechanical properties for the PCA-CPC cements were observed by the combined use
      of 8% (w/w) stannous fluoride and 10% (w/w) tartaric acid. The mechanical
      properties of the PCA-CPC cement also were improved by adding calcium acetate,
      calcium methacrylate, zirconium(IV) sulfate and phosphonoacetic acid.

PMID- 8299871
TI  - Fracture toughness, diametrical strength, and fractography of amalgam and of
      amalgam to amalgam bonds.
AB  - Chevron-notch fracture toughness, diametrical tensile strength and fractography
      were evaluated for bulk amalgams and for bonds formed between new and 1-day-old
      amalgams of the same type. Three types of bonded specimens were prepared: 1) by
      mechanically roughening the 1-day-old amalgam with 600-grit paper; 2) using a new
      mercury-rich amalgam; and 3) using a bonding resin, either 4-META or a phosphate
      ester monomer. Similar values in bond properties were obtained with all bonding
      techniques for two commercial dispersed-phase bonded amalgams, one of which
      contained palladium; however, bulk fracture toughness of the palladium-containing
      amalgam was significantly less than for the palladium-free amalgam. This result
      reveals that the bonding of amalgam to amalgam, at least for these two amalgams,
      is a surface-related phenomenon, and thus, the traditional reporting of bonding
      properties as a percentage of bulk properties loses meaning. Short-rod geometry
      was more representative of the interfacial bond properties since these samples
      fractured within the interfacial bonds, while diametrical strength samples often
      fractured slightly away from the interface. The use of bonding resins did not
      improve bond fracture toughness for either amalgam, while the diametrical
      strength improved for one of the amalgams. The use of mercury-rich amalgam
      significantly improved the fracture toughness over all other techniques for one
      amalgam while proving to be similar to a 600-grit preparation for the second
      amalgam.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299872
TI  - Early strength of glass ionomer cements.
AB  - The present study compared the compressive, tensile and flexural strengths of 26
      commercial glass ionomer cements, which were evaluated 24 h after the beginning
      of the setting reaction. In order to give a global estimation of their overall
      strength, a coefficient was attributed to each glass ionomer cement. This
      strength coefficient provided a ranking of the tested materials. The highest
      scores were obtained by the restorative glass ionomers; however, these materials
      exhibited lower mechanical properties than the more classic restorative materials
      such as amalgams or composites. The results also showed a large scattering of the
      mechanical properties among the luting and lining glass ionomer cements. The
      creep behavior of the glass ionomer cements was also investigated.

PMID- 8299873
TI  - Cusp movement in premolars resulting from composite polymerization shrinkage.
AB  - This study examined the effect of cavity size, hydration conditions and type of
      composite on cusp movement following placement of MOD composite restorations in
      vitro. A microscope with a micrometer stage was used to measure deflection of
      cusps for 14 days after initiation of curing. The intercuspal width decreased for
      the first few minutes after the composites were placed, then increased toward the
      original dimensions. Teeth with small cavities contracted less than those with
      large cavities, and recovery was complete or nearly complete only in teeth with
      small cavities. Hydrated teeth and restorations recovered more rapidly and more
      completely than those that were dry. Differences in deflection of the cusps were
      observed with two different restorative materials.

PMID- 8299874
TI  - Effect of home-use fluoride gels on glass ionomer and composite restorations.
AB  - The effect of home-use topical fluorides on the surface integrity of two glass
      ionomers and a composite was studied using SEM. Class V cavities prepared in
      extracted teeth were restored with two commercial glass ionomers and a composite.
      Teeth were randomly divided into groups and each group treated for 24 h with one
      of the following fluoride gels: acidulated phosphate fluoride (pH5), stannous
      fluoride (pH4.5), sodium fluoride (pH7), and a non-proprietary sodium fluoride
      (pH5.8). Surface degradation of the restorations was studied using SEM, rated
      according to specific criteria, and statistically analyzed by the Wilcoxon test
      (Rank Sums). It was found that the APF and the non-proprietary gel had a
      significant effect on both Gl matrix and particles and on the composite particles
      (p < 0.01). The neutral sodium fluoride had no significant effect on the
      materials (p > 0.01).

PMID- 8299875
TI  - Thermal conductivity of cement base materials.
AB  - This study was designed to determine the most efficient dentin-cement-restorative
      material system to minimize temperature changes from either a hot (58 degrees C)
      or cold (4 degrees C) source. Extracted human molar teeth were used to conduct
      the experiment utilizing a standard Class I occlusal preparation 3.5 mm in
      diameter with a remaining dentin thickness of 0.5 or 1.0 mm and a control dentin
      thickness of 2.0 mm. A bi-electrode thermocouple was utilized with one
      thermocouple mounted on the roof of the pulp chamber and the other on the
      occlusal surface of the specimen. The cements investigated were zinc oxide and
      eugenol (ZOE), zinc phosphate (ZP), glass ionomer (GI), and zinc polycarboxylate
      (ZPC) with a thickness of either 0.5 mm or 1.5 mm. Statistical analysis consisted
      of a one-way analysis of variance followed by a multiple means comparison test.
      For heated specimens consisting of cement and dentin only, ZOE was the least
      effective in limiting temperature change. When cold was applied, ZOE was the most
      effective. Statistically for cold application, the other three cements, ZP, GI
      and ZPC, and 2.0 mm of dentin were the same for limiting temperature change. When
      amalgam was used to restore the tooth, ZOE and GI were most effective in limiting
      temperature change for cooled teeth. For heated teeth, all the cements were
      identical except for ZOE, which was the least effective. For composite restored
      teeth, all cements and dentin were identical in limiting temperature changes for
      either heating or cooling.

PMID- 8299876
TI  - Calponin and SM 22 as differentiation markers of smooth muscle: spatiotemporal
      distribution during avian embryonic development.
AB  - Calponin and SM 22 are two proteins related in sequence that are particularly
      abundant in smooth muscle cells. Here, the distribution patterns of calponin and
      SM 22 were compared with that of other smooth muscle contractile and cytoskeletal
      components in the avian embryo using immunofluorescence microscopy and
      immunoblotting. Like myosin-light-chain kinase and heavy caldesmon, both calponin
      and SM 22 were more or less exclusively found in smooth muscle cells, during
      embryonic development and in the adult. Labelling of other cell types including
      striated muscle was not observed. In contrast, tropomyosin, smooth muscle alpha
      actin, filamin and desmin could also be detected in many other cell types in
      addition to smooth muscles, at least during part of embryonic life. Calponin and
      SM 22 appeared almost synchronously during the differentiation of all smooth
      muscle cell populations, though with a slight time difference in the case of the
      aorta. The appearance of calponin, SM 22 and heavy caldesmon was generally
      delayed in relation to desmin, tropomyosin, smooth muscle alpha-actin, myosin
      light-chain kinase and filamin and a marked increase in abundance of these
      proteins was observed in the late embryo and in the adult. From these
      observations we can conclude that both calponin and SM 22 belong to a group of
      late differentiation determinants in smooth muscle and may constitute convenient
      and reliable markers to follow the differentiation of most, if not all, smooth
      muscle cell populations.

PMID- 8299877
TI  - Common antigen of oval and biliary epithelial cells (A6) is a differentiation
      marker of epithelial and erythroid cell lineages in early development of the
      mouse.
AB  - The A6 antigen--a surface-exposed component shared by mouse oval and biliary
      epithelial cells--was examined during prenatal development of mouse in order to
      elucidate its relation to liver progenitor cells. Immunohistochemical
      demonstration of the antigen was performed at the light and electron microscopy
      level beginning from the 9.5 day of gestation (26-28 somite pairs). Up to the
      11.5 day of gestation A6 antigen is found only in the visceral endoderm of yolk
      sac and gut epithelium, while liver diverticulum and liver are A6-negative. In
      the liver epithelial lineages A6 antigen behaves as a strong and reliable marker
      of biliary epithelial cells where it is found beginning from their emergence on
      the 15th day of gestation. It was not revealed in immature hepatocytes beginning
      from the 16th day of gestation. However weak expression of the antigen was
      observed in hepatoblasts on 12-15 days of gestation possibly reflecting their
      ability to differentiate along either hepatocyte or biliary epithelial cell
      lineages. Surprisingly, A6 antigen turned out to be a peculiar marker of the
      crythroid lineage: in mouse fetuses it distinguished A6 positive liver and spleen
      erythroblasts from A6 negative early hemopoietic cells of yolk sac origin.
      Moreover in the liver, A6 antigen probably distinguishes two waves of
      erythropoiesis: it is found on the erythroblasts from the 11.5 day of gestation
      onward while first extravascular erythroblasts appear in the liver on the 10th
      day of gestation. Both fetal and adult erythrocytes are A6-negative. In the
      process of organogenesis A6 antigen was revealed in various mouse fetal
      organs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299878
TI  - Specific expression in adult mice and post-implantation embryos of a transgene
      carrying the histone H1(0) regulatory region.
AB  - Histone H1(0), a variant of the H1 group, has been found associated with the
      repressed state of chromatin and its content is increased in terminally
      differentiated cells. We have cloned a mouse H1(0) histone gene and introduced
      the promoter region, ligated to the beta-galactosidase reporter gene, into
      transgenic mice. By histochemistry we demonstrated a strong expression of the
      transgene in adult kidney, testis and brain. Intestine, uterus and ovarium were
      also positive. This expression followed the same pattern as that of the
      endogenous H1(0) gene, as demonstrated by in situ hybridization with a non-coding
      fragment of the mRNA, by Northern analysis, and by immunofluorescence with
      specific antibodies. In post-implantation embryos, the expression was very low up
      to day ten p.c. At this time, most of the X-Gal staining was found in the brain,
      retina and some of the large blood vessels. Hence, expression of the transgene as
      well as of the endogenous H1(0) gene is not exclusively linked to a
      differentiated phenotype or to a reduced cell proliferation capacity.

PMID- 8299879
TI  - Mixed parenchymal-stromal populations of rat adrenocortical cells support the
      proliferation and differentiation of steroidogenic cells.
AB  - The mechanisms which regulate adrenocortical steroidogenesis in differentiated
      parenchymal cells have been studied in great detail. However, the stem cells that
      are responsible for regeneration of the adult cortex have never been identified
      or isolated, and their characteristics are unknown. We have developed a tissue
      culture system that supports the simultaneous proliferation and differentiation
      of steroidogenic adrenocortical cells. Utilizing density gradient separation, a
      cell population composed of a mixture of stromal, endothelial and parenchymal
      cells (MIX) was isolated from the adult rat adrenal cortex. In primary culture,
      MIX populations formed high saturation density multilayers from which rounded
      cells emerged. These cells proliferated, contained lipid, and expressed the
      steroidogenic enzymes delta 5,3 beta-hydroxysteroid dehydrogenase and cholesterol
      side-chain cleavage cytochrome P-450scc. After selective passaging, rounded MIX
      derived cells retained their steroidogenic potential, even in the absence of
      trophic hormone treatment. In contrast, parenchymal cells obtained from the zonae
      fasciculata (FASC) and glomerulosa (GLOM) respectively, formed homogeneous
      monolayers in primary culture, gradually de-differentiated, and no longer
      responded to trophic hormone treatment after passaging. Thus, primary MIX
      cultures provided a microenvironment that resulted in the production of
      adrenocortical cells with stem cell-like qualities. These cultures provide for
      the first time, a system for the identification of specific inducers that are
      responsible for both adrenocortical cytogenesis and its associated proliferation
      and steroidogenic differentiation.

PMID- 8299881
TI  - Nutrient-gene interactions: today and tomorrow.

PMID- 8299880
TI  - Transforming growth factor-beta 1, beta 2, and beta 3, urokinase and parathyroid
      hormone-related peptide expression in 8701-BC breast cancer cells and clones.
AB  - 8701-BC is a recently characterized cell line isolated from a primary ductal
      infiltrating carcinoma of the breast (d.i.c.), showing some pleomorphism in cell
      microanatomy at an ultrastructural level. We have obtained different sublines of
      8701-BC cells by cloning in soft agar at different concentrations (0.3% and
      0.6%), and we have characterized the cloned lines by some morphological and
      growth parameters. 8701-BC cells and clones have been submitted to analysis by
      reverse transcriptase-linked polymerase chain reaction to detect mRNAs of various
      cytokines (transforming growth factor-beta s, tumour necrosis factors,
      interleukin 1s, interleukin 6, parathyroid hormone-related peptide, gamma
      interferon) and of urokinase, which are bioactive molecules commonly involved in
      cell-cell and cell-stroma interactions at primary and/or secondary sites of
      invasion. The aims of the present investigation were to determine: (a) if the
      corresponding genes are active in 8701-BC cell line and (b) if the sublines
      tested exhibit transcriptional heterogeneity. The results obtained show that 8701
      BC cells express transcripts of transforming growth factor-beta s, urokinase and
      parathyroid hormone-related peptide (PTHrP), the latter product being responsible
      for the cancer-associated humoral hypercalcemic syndrome. Moreover, while the
      first two mRNAs are detectable in all the sublines tested, PTHrP is expressed
      almost uniquely by the clones isolated in 0.6% agar which exhibit a peculiar
      morphological appearance, a higher growth rate and a more active invasive
      behaviour in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8299882
TI  - Glucose induced genes in bovine aortic smooth muscle cells identified by mRNA
      differential display.
AB  - Hyperglycemia is postulated to cause chronic changes in the vasculature of
      diabetic patients, suggesting structural or genetic alterations. We have
      characterized the glucose induced alterations of gene expression in cultured
      bovine aortic smooth muscle cells using the recently developed mRNA differential
      display method. After five days of incubation with either 5.5 or 22 mM glucose,
      RNA preparations were isolated from confluent cells and probed with 10 candidate
      clones identified after screening up to 3000 mRNA species. Among these, three
      clones (2A, 2C, 3) showed significant changes in expression by Northern blot
      analysis. Elevated glucose levels decreased the mRNA expression of clones 2A and
      3 to 51 +/- 7% (P < .01) and 59 +/- 10% (P < .05) (mean% of control +/- SEM),
      respectively. Expression of clone 2C was increased in 22 mM glucose condition to
      221 +/- 23% (P < .05). Nucleotide sequence analysis showed that clone 3 had 77%
      homology to the 3'-noncoding region of human elongation factor 2, a member of the
      GTPase family which is essential for polypeptide synthesis. Clones 2A and 2C do
      show no homology to known nucleotide sequences. These results indicate that
      physiologically attainable high glucose conditions can significantly effect gene
      expression in aortic smooth muscle cells. Furthermore, mRNA differential display
      can be used in metabolic studies to identify new genes regulated by nutrients
      such as glucose.

PMID- 8299883
TI  - A partially active mutant aldolase B from a patient with hereditary fructose
      intolerance.
AB  - Hereditary fructose intolerance (HFI) is a potentially fatal autosomal recessive
      disease of carbohydrate metabolism. HFI patients are deficient in aldolase B, the
      isozyme expressed in fructose-metabolizing tissues. The eight protein coding
      exons, including splicing signals, of the aldolase B gene from one American HFI
      patient were amplified by the polymerase chain reaction (PCR). Single-strand
      conformational polymorphism (SSCP) analysis and direct sequence determination
      were applied to the amplified fragments. The mutations in the patient's alleles
      were identified as a nonsense mutation (R59op) in exon 3 and a missense mutation
      (C134R) in exon 5. These mutations were confirmed by sequence determination of
      cloned PCR-amplified exons 3 and 5 from the patient. Allele specific
      oligonucleotide (ASO) hybridizations of amplified exons 3 and 5 showed the
      Mendelian inheritance of both mutations. Site-directed mutagenesis was used to
      generate an expression plasmid for the C134R mutation, and the mutant enzyme was
      expressed in bacteria. Assays of partially purified enzyme preparations showed
      that this missense mutation results in an apparently unstable enzyme that retains
      partial activity. This is the first evidence for a partially active aldolase B
      from an HFI individual with an identified mutation, and supports the hypothesis
      that adequate gluconeogenesis/glycolysis is maintained in HFI patients by the
      presence of partially active enzymes.

PMID- 8299884
TI  - Low-density lipoprotein subclass patterns and lipoprotein response to a reduced
      fat diet in men.
AB  - Low-density lipoprotein (LDL) subclass pattern B is a common genetically
      influenced lipoprotein profile characterized by a predominance of small, dense
      LDL particles, and associated with increased levels of triglyceride-rich
      lipoproteins, reductions in high-density lipoprotein cholesterol (HDL-C), and
      increased risk of coronary artery disease compared to individuals with a
      predominance of larger LDL (pattern A). We sought to determine whether LDL
      subclass patterns are associated with response of plasma lipoprotein levels to
      changes in dietary fat and carbohydrate content. In a randomized cross-over
      study, 105 men consumed, for six weeks each, high-fat (46%) and low-fat (24%)
      solid food diets, with replacement of fat by carbohydrate. Diet-induced changes
      in subjects who exhibited pattern B (n = 18) following the high-fat diet differed
      significantly from those in subjects with pattern A (n = 87): in pattern B
      subjects LDL cholesterol (LDL-C) reductions were two-fold greater and plasma
      apolipoprotein (apo) B levels decreased significantly. These differences remained
      significant after adjustment for levels of plasma LDL-C, apo B, HDL-C, and body
      mass index. Thus, LDL subclass pattern is a factor that contributes significantly
      to interindividual variation of plasma lipoprotein response to a low-fat, high
      carbohydrate diet.

PMID- 8299885
TI  - Amino acid-regulated gene expression in eukaryotic cells.
AB  - Given the central role of protein synthesis in cellular function, it is likely
      that intricate mechanisms exist to detect and respond to amino acid deprivation.
      However, the current understanding of amino acid-dependent control of gene
      expression in mammalian cells is limited. A few examples of enzyme, transporters,
      and unidentified mRNA species subject to amino acid availability have been
      reported and some examples are summarized here. Each example chosen-asparagine
      synthetase, system A transport activity, and ribosomal protein L17--are
      associated with different aspects of amino acid metabolism, and therefore reflect
      the spectrum of metabolic pathways influenced by substrate control. Most of the
      data accumulated thus far suggest that a general control response exists such
      that these various activities are induced when any one of several amino acids
      becomes limiting. Consistent with observations in yeast, it appears that the
      degree of tRNA acylation and its resultant effect on protein synthesis may play
      an important role in initiating the starvation signal. De novo protein synthesis
      is required for starvation-dependent increases in several mRNA species, which
      suggests that the amino acid signaling pathway is composed of a series of
      intermediate steps before activation of specific structural genes.

PMID- 8299886
TI  - The case of the disappearing silver.

PMID- 8299887
TI  - Nutrient regulation of insulin gene expression.
AB  - The beta cell of the islets of Langerhans contributes along with other factors to
      glucose homeostasis by sensing changes in the plasma glucose concentrations and
      adjusting the rate of insulin production and release. Over short periods of time,
      insulin production is controlled principally through translation of pre-existing
      mRNA. Over longer periods, insulin mRNA levels are modulated through effects on
      the rate of transcription of the insulin gene, and also through changes in the
      rate of decay of insulin mRNA. These long-term effects may be important in
      allowing the beta cell to adapt to changes in diet or periods of fasting. Several
      mechanisms involved in the control of the rate of translation of insulin mRNA
      have been described. Effects of glucose metabolism on the turnover of insulin
      mRNA have yet to be characterized in detail. At the level of transcription, cis
      acting DNA elements and trans-acting factors involved in the transient response
      of the insulin gene to changes in intracellular cAMP levels, or to signals
      generated as a result of glucose metabolism, have been identified.

PMID- 8299888
TI  - Transcriptional control of metabolic regulation genes by carbohydrates.
AB  - Glucose can modulate the transcription of many genes, particularly those encoding
      enzymes of liver metabolism. The transcriptional effect of glucose can be
      indirect, being mediated in vivo by hormonal variations, especially increase in
      insulin and decrease in glucagon secretion. Whereas the transcription of the
      glucokinase gene, for example, is stimulated by insulin without the aid of
      glucose, the transcriptional activation of most glycolytic and lipogenic genes in
      hepatocytes requires the presence of both glucose and insulin. The role of
      insulin in the activation of these genes seems mainly to stimulate glucokinase
      synthesis, and thus to permit glucose phosphorylation. In some cells in which
      hexokinase activity is constitutive, the glucose-dependent activation of the same
      genes does not require insulin and, in addition, can be produced by the
      nonmetabolisable analog, 2-deoxyglucose. In hepatocytes, the insulin effect on
      the glucose-dependent activation of the L-pyruvate kinase gene can be reproduced
      by fructose at low concentrations. Fructose probably acts through the fructose 1
      phosphate dependent deinhibition of glucokinase activity. A glucose/carbohydrate
      element has been identified on the L-type pyruvate kinase and spot 14 gene
      promoters. It is able to bind, in vitro, transcriptional factors of the MLTF/USF
      family and could act in cooperation with tissue-specific contiguous elements,
      such as the HNF4 binding site in the L-type pyruvate kinase gene.

PMID- 8299889
TI  - Regulation of expression of glucose transporters by glucose: a review of studies
      in vivo and in cell cultures.
AB  - Glucose transporters are membrane-embedded proteins that mediate the uptake of
      glucose from the surrounding medium into the cell. Glucose is the main fuel for
      most cells, and its uptake is rate-limiting for glucose utilization. For this
      reason, it is expected that glucose transport is tightly regulated. Whereas rapid
      regulation of glucose transporters by hormones has been known for some time, the
      regulation of glucose transporters by substrate availability (i.e., by glucose
      itself) is less well understood. This question has been approached by scientists
      from two angles: one, by measuring the consequence of diabetic states (in which
      there is surplus of glucose availability) on the expression of glucose
      transporter genes, and another one, by measuring the effect of glucose
      availability and glucose deprivation in cell cultures on glucose transporter gene
      expression. The results from both camps are unfortunately not coincident, due in
      part to the coexistence of other variables in the diabetic animals, and to the
      lack of ideal cell cultures. In spite of these caveats, the profuse literature on
      both approaches propelled us to find commonalities within each approach. This
      review concludes that in animal studies, one isoform of glucose transporters, the
      GLUT4 type, is down-regulated by high levels of circulating glucose in muscle but
      not in fat cells. This down-regulation of the protein is independent of
      regulation of transcription. In contrast, in fat cells, high glucose levels
      depress GLUT4 mRNA levels. In cell culture studies, high glucose levels lead to
      lower expression of the GLUT1 transporter isoform relative to glucose-deprived
      cultures. Glucose levels do not affect the amount of GLUT4 transporter isoform.
      The down-regulation of the GLUT1 transporter protein is caused by pre- and post
      transcriptional mechanisms, the prevalence of each being cell-type specific. No
      glucose-responsive elements have been identified on either the GLUT1 or GLUT4
      genes, and no information is available on the glucose metabolites that mediate
      the response of glucose transporter gene expression to glucose availability.

PMID- 8299890
TI  - Interactive regulation of the pyruvate dehydrogenase complex and the carnitine
      palmitoyltransferase system.
AB  - The review examines the mechanisms regulating the activities of the two key
      enzymes determining rates of glucose and fatty acid oxidation, i.e., the pyruvate
      dehydrogenase (PDH) complex and the carnitine palmitoyltransferase (CPT) system.
      The review also evaluates the regulatory importance of gene expression in the
      control of tissue fuel selection within the context of substrate competition
      between glucose and fatty acids. It identifies a strong indirect input of
      nutrient-gene interactions in the control of pyruvate oxidation through the
      regulated provision of pyruvate as a substrate for PDH and as an inhibitor of PDH
      kinase. Nutrient-gene interactions are also identified in relation to the
      regulation of CPT I activity by malonyl-CoA (inhibitor) and by the provision of
      long-chain acyl-CoA (substrate/activator), the latter via the hydrolysis of
      plasma or tissue triacylglycerol (by lipoprotein lipase and hormone-sensitive
      lipase, respectively). We discuss how such regulation is reinforced by long-term
      modulation of PDH kinase-specific activity and CPT I maximal activity. We also
      explore the role of mechanisms operating at the levels of the PDH complex and the
      CPT system that act to promote and accelerate a switch in fuel utilization once a
      committed change in nutrient supply has been established. In particular, we
      discuss the regulatory influences exerted by altered sensitivities of PDH kinase
      to inhibition by pyruvate and CPT I to inhibition by malonyl-CoA, respectively.

PMID- 8299891
TI  - Nutritional regulation of hormones and growth factors that control mammalian
      growth.
AB  - Juvenile animals stop growing if they are fed a diet containing an inadequate
      amount of energy or protein. The molecular basis for this growth arrest is not
      completely understood. The cessation of growth that occurs in nutritionally
      restricted animals is not generally explained by a decrease in circulating growth
      hormone (GH). In most species, plasma GH is increased rather than decreased under
      conditions of nutritional restriction. Current evidence suggests that the
      biosynthesis of insulin-like growth factor-I (IGF-I) is a key control point for
      nutritional regulation of growth. Plasma IGF-I peptide levels and hepatic IGF-I
      mRNA abundance are correlated with growth velocity and are consistently decreased
      when growth is arrested by nutritional deprivation. The decreased IGF-I mRNA
      abundance observed in the fasting rat appears to be caused primarily by a
      decrease in IGF-I gene transcription. In tissues and plasma, the insulin-like
      growth factors are complexed with high-affinity binding proteins, which are
      thought to modulate the tissue access and action of the IGFs. The hepatic mRNA
      abundance of two of the binding proteins (IGFBP-1 and -2) is increased in
      nutritionally restricted animals. This increase in mRNA abundance is caused
      primarily by an increase in transcription of the IGFBP-1 and IGFBP-2 genes.
      Current research is focused on molecular mechanisms for regulation of IGF-I and
      IGF-binding protein gene expression.

PMID- 8299892
TI  - Aldolase B and fructose intolerance.
AB  - Hereditary fructose intolerance is an autosomal recessive disorder that
      illustrates vividly the interplay between heredity and environment in the genesis
      of human nutritional disease. Genetically determined defects of an isozyme of
      fructose bisphosphate aldolase (aldolase B, which is specialized for the
      metabolic assimilation of dietary sugars) predispose to this widely distributed
      condition. Ingestion of fructose, sorbitol, or sucrose induces abdominal pain,
      vomiting, and metabolic disturbances--including low concentrations of blood
      glucose--that may prove fatal. The response to dietary exclusion is rapid and,
      when so treated, the disease is compatible with a normal life span. A noteworthy
      feature of the condition in individuals who survive the stormy period of weaning
      is the development of powerful aversions to fruit, nuts, and sweet-tasting foods
      and drinks. The incidence of dental caries is consequently much reduced.

PMID- 8299893
TI  - Abnormal A1 adenosine receptor function in genetic obesity.
AB  - Obesity is increasingly recognized as an important health problem in developed,
      industrialized countries. As a large proportion of the variance in individual
      adiposity is based on genetic factors (1-3), recent efforts have focused on
      identifying genes involved in regulating the percentage of body fat in a given
      individual. This effort is helped by the existence of rodent models of genetic
      obesity. Many strains of mice and at least three rat strains have been identified
      thus far that exhibit inherited obesity accompanied by a similar set of endocrine
      abnormalities (4). Although the symptoms of the disease are similar in different
      strains, different genes appear to be involved in causing the syndrome, as the
      mutation responsible for the obesity maps to different chromosomal sites in the
      different strains. Efforts to find the products of the mutated genes over the
      past 30 years have generally been unsuccessful. However, the available data imply
      that many obesity mutations may involve genes that code for proteins in a single
      signal transduction pathway or one particular cascade of covalent modification.
      Reasonable theories are plentiful about the identity of such a pathway, but
      current studies in the laboratories of the authors suggest that the A1 adenosine
      receptor signaling pathway may be involved. Evidence of abnormal A1 receptor
      function has been obtained from studies of Zucker rats and obese (ob/ob) mice (5
      7). These strains are obese because of a single recessive mutation. Measurements
      of adenylyl cyclase activity and regulation in isolated adipocytes and isolated
      plasma membranes suggest that the receptor is unusually and tonically active in
      obese rats. Because signaling from this receptor inhibits lipolysis in white and
      brown fat, induces insulin resistance in skeletal muscle (8, 9), but increases
      insulin sensitivity in adipose tissue (10, 11), the possibility arises that the
      excessive activity of the A1 adenosine receptor may induce obesity. Data from
      human volunteers are also compatible with the possibility that the activity of
      the receptor is unusually high in vivo in obese individuals (12).

PMID- 8299894
TI  - Glucose-dependent regulation of the L-pyruvate kinase gene in a hepatoma cell
      line is independent of insulin and cyclic AMP.
AB  - Hepatocyte-like mhAT3F cells have been derived from the hepatoma of a transgenic
      mouse expressing the SV40 large T antigen under the control of the antithrombin
      III gene regulatory region (Antoine, B., Levrat, F., Vallet, V., Berbar, T.,
      Cartier, N., Dubois, N., Briand, P., and Kahn, A. (1992) Gene expression in
      hepatocyte-like lines established by targeted carcinogenesis in transgenic mice.
      Exp. Cell. Res. 200, 175-185; F. Levrat et al., unpublished results). In these
      cells, the L-PK gene is transcriptionally activated by glucose, as it is in vivo
      and in cultured hepatocytes. However, in contrast to the L-PK gene regulation in
      the liver and isolated hepatocytes, the glucose responsiveness does not require
      insulin and is not blocked by cyclic AMP. In mhAT3F cells, the insensitivity to
      insulin might be due to the replacement of insulin-dependent glucokinase by
      insulin-independent hexokinases able to phosphorylate glucose in the absence of
      the hormone. The glucose-dependent activation of the L-PK gene is delayed,
      requires ongoing protein synthesis, and is mediated by the same glucose response
      element as in vivo and in isolated hepatocytes. These results suggest that the
      glucose-dependent signaling pathway responsible for the transcriptional
      activation of glycolytic and lipogenic genes requires glucose phosphorylation, a
      phenomenon that is insulin-dependent in the liver but insulin-independent in
      cultured hepatoma cells. Nevertheless, the action of glucose 6-phosphate is most
      likely indirect.

PMID- 8299895
TI  - Dietary copper deficiency reduces heat shock protein expression in cardiovascular
      tissues.
AB  - Dietary copper deficiency impairs cardiovascular function by depression of
      catecholamine metabolism, and alteration of the structure and function of cardiac
      mitochondria. Heat shock proteins (HSPs) are a group of cellular homeostatic
      proteins that are induced in vascular tissue by catecholaminergic transmission
      after exposure to stress. We investigated the effects of dietary copper
      deficiency on the induction and accumulation of HSPs in several cardiovascular
      tissues. Stress-induced levels of aortic HSP70 mRNA were reduced in copper
      deficient (CuD) rats when compared with copper-adequate (CuA) controls. Cocaine
      induced HSP70 mRNA accumulation was not different between CuA and CuD rats,
      suggesting that reduced HSP70 levels in restrained CuD animals may result from
      altered catecholaminergic neurotransmission. The level of HSP60 mRNA was
      specifically reduced in the atria of CuD rats, which may be associated with
      altered mitochondrial structure and function. These results describe a novel
      relationship between dietary copper deficiency and the expression of highly
      conserved cellular stress response proteins. Loss of these essential homeostatic
      proteins in vascular tissue may contribute to the impairment of cardiovascular
      function known to accompany copper deficiency.

PMID- 8299896
TI  - Quality of life: a valid and reliable measure of therapeutic efficacy in the
      treatment of inflammatory bowel disease. Canadian Crohn's Relapse Prevention
      Trial Study Group.
AB  - BACKGROUND/AIMS: Quality of life (QOL), a subjective index of health perception
      and function, embraces physical, social, and emotional performance but has not
      had a prominent role in clinical trials of inflammatory bowel disease (IBD). To
      test the robustness of the Inflammatory Bowel Disease Questionnaire (IBDQ), a
      disease-specific QOL index, this study assessed its validity, reliability, and
      responsiveness during a multicenter trial. METHODS: Three hundred five patients
      with stable Crohn's disease received cyclosporin or placebo for 18 months. IBDQ
      and dimensional scores (bowel, social, systemic, and emotional) were correlated
      with disease activity (Crohn's disease activity index [CDAI] and Harvey-Bradshaw
      index). Concordance of IBDQ scores was tested in 280 stable subjects. Linear
      regression evaluated change in IBDQ scores over time. RESULTS: IBDQ scores
      correlated highly with CDAI (r = -0.67; P < 0.0001). The reliability coefficient
      for IBDQ score was 0.70 vs. 0.66 for CDAI and 0.55 for Harvey-Bradshaw index.
      Regression line slopes of IBDQ scores were significantly different in patients
      who deteriorated from those who remained stable ([b] < 0.15; P < 0.0001). QOL
      scores were lower in patients who required surgery. CONCLUSIONS: The IBDQ is a
      valid reliable assessment tool that reflects important changes in the health
      status of patients with IBD. The IBDQ is a robust measure of therapeutic efficacy
      and should be used in future clinical trials in IBD.

PMID- 8299897
TI  - Eicosanoid production by a differentiated canine colonic epithelial cell line,
      VNCC.
AB  - BACKGROUND/AIMS: The lack of pure, proliferative, but not transformed intestinal
      epithelial cells has impeded progress in understanding their role in chronic
      intestinal inflammation. To clarify that role, the present study characterized
      the epithelial cell line VNCC, derived from normal adult dog distal colon.
      METHODS: Cells were cultured on plastic and permeable supports for analysis of
      eicosanoid production (by radioimmunoassay and high-performance liquid
      chromatography) and transport characteristics (by Ussing chamber short-circuit
      determinations). RESULTS: In culture, VNCC formed confluent monolayers and domes,
      suggesting formation of tight junctions and active solute absorption. When
      cultured on permeable supports, VNCC developed modest, but variable,
      transepithelial resistances (563 +/- 94 omega/cm2) with a spontaneous short
      circuit current of 5.0 +/- 0.4 microA/cm2. Forskolin caused a prolonged increase
      in the short-circuit current, inhibited by amiloride but not bumetanide,
      suggesting that VNCC display 5'-cyclic adenosine monophosphate-stimulated sodium
      absorption. VNCC incubated with arachidonic acid released a variety of
      eicosanoids including 6-keto-prostaglandin (PG)F1 alpha, PGE2, thromboxane B2,
      and PGF2 alpha, but no hydroxyarachidonate metabolites. Bradykinin stimulated
      VNCC eicosanoid release. CONCLUSIONS: The ability of VNCC to divide and
      differentiate in culture, to form polarized monolayers capable of active sodium
      absorption, and to respond to inflammatory mediators with eicosanoid release
      makes them a unique tool for the study of the interactions of inflammation on
      colonocyte function.

PMID- 8299898
TI  - Role of Shiga-like toxin I in bacterial enteritis: comparison between isogenic
      Escherichia coli strains induced in rabbits.
AB  - BACKGROUND/AIMS: Enteroadherent Escherichia coli that produce Shiga-like toxins
      are important causes of human disease, including enterohemorrhagic E. coli
      induced colitis (EHEC). The role of Shiga-like toxins in these illnesses is
      unclear. The aim of this study was to establish an animal model for human EHEC
      and to determine the role of Shiga-like toxin I (SLT-I) in this model. METHODS:
      E. coli strain RDEC-1 is an enteroadherent rabbit diarrheal pathogen. An isogenic
      variant of RDEC-1 (termed RDEC-H19A) producing high levels of SLT-I was obtained
      by infecting RDEC-1 with an SLT-I-converting bacteriophage. The effects of in
      vivo enteric infection produced in rabbits by RDEC-H19A were compared with those
      in uninfected and RDEC-1-infected animals. RESULTS: SLT-I-producing RDEC-H19A
      induced a severe, noninvasive, enteroadherent infection in rabbits. Clinically,
      infection with RDEC-H19A was more severe than infection with RDEC-1 and caused
      more serious histological lesions including vascular changes, edema, and more
      severe inflammation. Interleukin 1 and platelet-activating factor appear to be
      important inflammatory mediators to this infection. CONCLUSIONS: The illness
      induced by RDEC-H19A in rabbits resembled enterohemorrhagic E. coli-induced
      colitis of humans. SLT-I is an important virulence factor in the pathogenesis of
      EHEC.

PMID- 8299899
TI  - The effect of intestinal hypoperfusion on intestinal absorption and permeability
      during cardiopulmonary bypass.
AB  - BACKGROUND/AIMS: Mean arterial pressure is reduced during hypothermic
      cardiopulmonary bypass. The aim of this study was to assess whether this was
      associated with intestinal hypoperfusion and whether it affected intestinal
      absorption and permeability. METHODS: Twenty-six patients undergoing coronary
      artery bypass grafting underwent an intestinal absorption-permeability test
      involving ingestion of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose.
      Ingestion took place 2 days before, within 3 hours, and 5 days after hypothermic
      cardiopulmonary bypass. Hemodynamic parameters and gastric mucosal laser Doppler
      blood flow were measured perioperatively in eight patients. RESULTS: Hypothermic
      (28 degrees C), nonpulsatile cardiopulmonary bypass resulted in a 25% reduction
      in mean blood pressure, 10% reduction in cardiac index, and a 46% reduction in
      gastric mucosal laser Doppler blood flow. There was 85.4%, 85.5%, and 73.6%
      reduction (P < 0.01) in active (3-O-methyl-D-glucose) and passive (D-xylose)
      carrier-mediated transport and passive, nonmediated transcellular (L-rhamnose)
      transport in the immediate postoperative period, respectively. The differential
      urine excretion of lactulose/L-rhamnose increased sixfold. All parameters
      returned to control levels by the fifth postoperative day. CONCLUSIONS:
      Cardiopulmonary bypass, while maintaining generally acceptable levels of
      hemodynamic performance, is associated with significant intestinal hypoperfusion
      and malabsorption of monosaccharides, which may have implications for enteral
      drug treatment in the immediate postoperative period.

PMID- 8299900
TI  - Spasmolytic polypeptide: a trefoil peptide secreted by rat gastric mucous cells.
AB  - BACKGROUND/AIMS: Spasmolytic polypeptide (SP) is a trefoil peptide expressed in
      the digestive tract. This study aimed to determine the structure and distribution
      of SP expression in the rat gastrointestinal tract. METHODS: The structure of rat
      SP was determined from the sequence of complementary DNAs isolated from antral
      RNA. SP gene expression was localized by Northern blotting and in situ
      hybridization in the adult and fetal rat digestive tract. Expression of the SP
      peptide was localized by immunocytochemistry and Western blot analysis. RESULTS:
      SP messenger (m)RNA was found predominantly in the stomach with highest
      expression in the antrum. High levels of SP mRNA were expressed in the fetal
      stomach before gastrin and somatostatin expression. Surprisingly, SP mRNA and
      peptide did not colocalize in the gastric mucosa, SP mRNA being superficial to SP
      peptide immunoreactivity throughout the gastric mucosa. Abundant SP
      immunoreactivity was seen in the lumen of the gastric glands and the mucus layer
      adherent to the gastric mucosa, indicating luminal secretion. CONCLUSIONS: In the
      rat, SP is a peptide secreted predominantly from antral mucous cell. The high
      concentrations of SP in the adherent gastric mucus layer (approximately 10
      mumol/L) suggest that SP functions as a structural peptide rather than a
      regulatory peptide.

PMID- 8299901
TI  - The role of endogenous nitric oxide and platelet-activating factor in hypoxia
      induced intestinal injury in rats.
AB  - BACKGROUND/AIMS: Nitric oxide is an endothelium-derived relaxing factor that
      promotes capillary integrity, inhibits leukocyte adherence and activation, and
      scavenges oxygen radicals. Because these effects are important in experimental
      intestinal injury, we studied the role of NO inhibition on hypoxia-induced bowel
      necrosis in the rat and investigated the interaction between platelet-activating
      factor (PAF) and NO in this model. METHODS: Sprague-Dawley rats were treated with
      either hypoxia, NO synthase inhibition (NG-methyl-L-arginine [LNMA] or NG-nitro-L
      arginine methyl ester [L-NAME]), hypoxia+LNMA, hypoxia+LNMA+NO donors, or
      hypoxia+LNMA+PAF receptor inhibition. Evaluations included blood pressure,
      superior mesenteric artery blood flow, arterial blood gases, histological
      intestinal injury, intestinal myeloperoxidase activity, and intestinal PAF
      activity. RESULTS: We found that hypoxia alone for 90 minutes (10% O2, partial O2
      pressure = 45 mm Hg) or LNMA alone had no detrimental effects. However,
      hypoxia+LNMA together caused hypotension, metabolic acidosis, intestinal injury,
      increased intestinal myeloperoxidase activity, and elevated intestinal PAF
      concentrations that were prevented by exogenous L-arginine. Furthermore, the
      hypotension and intestinal injury was prevented by PAF receptor blockade.
      CONCLUSIONS: We conclude that endogenous NO protects the intestine from hypoxia
      induced inflammation and injury, and the balance between local PAF and NO
      modulates the outcome of hypoxia-stressed intestine.

PMID- 8299902
TI  - Rectal proliferation and polyp occurrence in patients with familial adenomatous
      polyposis after sulindac treatment.
AB  - BACKGROUND/AIMS: Sulindac, a nonsteroidal anti-inflammatory drug (NSAID),
      decreases the occurrence of polyps in patients with familial adenomatous
      polyposis (FAP). The effects of colectomy with ileorectal anastomosis (IRA) and
      sulindac treatment on rectal mucosa proliferation and polyp occurrence were
      examined in patients with FAP. METHODS: The number and size of rectal polyps were
      measured with colonoscopy. The labeling index, the percentage of labeled cells
      per crypt compartment, was assessed in rectal biopsy specimens with [3H]thymidine
      incorporation and autoradiography in 6 non-IRA and 14 IRA patients before and
      after treatment with 200 mg of sulindac/day for 60 days. RESULTS: The IRA
      patients had a lower labeling index and a decrease in the percentage of labeled
      cells in the upper compartment of the crypt (P < 0.01) relative to non-IRA
      subjects. Sulindac did not influence the labeling index and the distribution of
      labeled cells along the crypt. On the contrary, a dramatic decrease in the size
      and number of polyps was observed after sulindac treatment (P < 0.001).
      CONCLUSIONS: The persistence of a abnormal mucosal proliferation after sulindac
      therapy, in spite of the reduction of polyp number, suggests caution in assuming
      a lower risk of rectal cancer in patients with FAP.

PMID- 8299903
TI  - Endogenous nitric oxide in gastric alkaline response in the rat stomach after
      damage.
AB  - BACKGROUND/AIMS: The gastric mucosa responds to hypertonic NaCl by significantly
      decreasing acid secretion. This study examined the role of nitric oxide in this
      phenomenon. METHODS: A rat stomach was mounted in an ex vivo chamber and perfused
      with saline; then the potential difference (PD), pH, and acid and/or alkaline
      responses were measured before and after the application of 1 mol/L NaCl with or
      without pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor
      of NO biosynthesis. RESULTS: A dose of 1 mol/L NaCl caused a reduction in PD, a
      decrease in basal and histamine-stimulated acid secretion, and an increase in
      luminal HCO3-. Prior administration of L-NAME did not affect either the PD or the
      HCO3- response but significantly attenuated the inhibitory effect of 1 mol/L NaCl
      on acid secretion. This effect of L-NAME was antagonized by the simultaneous
      administration with L-arginine but not D-arginine. Histamine-stimulated acid
      secretion in the normal stomach was significantly reduced by the exogenous NO
      donor nitroprusside but not by L-NAME. CONCLUSIONS: NO is involved in the
      mechanism of the gastric alkaline response after damage with 1 mol/L NaCl.
      Irritation of the gastric mucosa by hypertonic NaCl may release endogenous NO,
      which in turn inhibits acid secretion and unmasks luminal alkalinization caused
      by HCO3- flux in the damaged portion.

PMID- 8299904
TI  - Mediation of the trophic effects of short-chain fatty acids on the rat jejunum
      and colon.
AB  - BACKGROUND/AIMS: Short-chain fatty acids (SCFAs) are trophic to small intestinal
      and colonic mucosa. This study determined whether SCFAs infused into the cecum
      out of continuity stimulated jejunal and colonic cellularity and whether these
      effects were mediated by the autonomic nervous system and/or enterotrophic
      hormones. METHODS: To eliminate direct trophic effects of SCFAs in contact with
      mucosa, 60 rats underwent cecal isolation with placement of an infusion catheter
      into the proximal cecum, formation of distal cecocutaneous stoma, and restoration
      of intestinal continuity with ileocolonic anastomosis. Rats underwent cecal
      denervation or remained normally innervated and received 1 of 3 infusions for 10
      days: SCFAs, saline, or no infusion. Twenty-four additional rats were assigned to
      the same groups but underwent infusion into the proximal colon (in circuit).
      RESULTS: Cecal infusion of SCFAs into innervated rats increased (P < 0.05)
      jejunal DNA, villous height, surface area, crypt depth, and gastrin without
      increasing colonic variables. In denervated rats, SCFAs did not significantly
      affect these variables. However, direct intracolonic infusions of SCFAs increased
      (P < 0.05) colonic mucosal DNA and crypt depth. CONCLUSIONS: Jejunotrophic
      effects of cecally infused SCFAs are mediated afferently by the autonomic nervous
      system and are associated with increased jejunal gastrin. SCFAs have local
      trophic effects on the colon.

PMID- 8299905
TI  - Cholinergic responses in the cat lower esophageal sphincter show regional
      variation.
AB  - BACKGROUND/AIMS: The lower esophageal sphincter (LES) pressure in humans is
      asymmetric; the highest pressure and the most significant cholinergic
      contribution occurs toward the left. The basis of this asymmetry was examined
      using the cat as a model. METHODS: The LES pressure profile was determined using
      a manometry catheter with four ports oriented at right angles. The LES was
      dissected into right and left halves with the latter including a contribution
      from the oblique gastric sling fibers. Isometric tension responses were studied
      in vitro. RESULTS: In vivo, both the initial LES pressure (31.8 +/- 4.0 mm Hg)
      and the decrease (79.9% +/- 6.4%) after intravenous atropine (100 micrograms/kg)
      were greatest in the leftward direction. In vitro, both halves of the LES
      developed similar spontaneous tension, but the increase in tension to carbachol
      was twofold greater on the left than the right. Eserine increased and atropine
      decreased initial tension by 25%-30% in both. Strips from either side relaxed in
      response to electrical stimulation but the response was more complete in strips
      from the right, whereas sodium nitroprusside produced similar relaxation in both.
      CONCLUSIONS: Regional differences in the LES pressure and its cholinergic
      component can be accounted for by differences in the in vitro properties of the
      LES muscle fiber groups.

PMID- 8299906
TI  - Increased tumorigenicity after differentiation of colon cancer cell line: absence
      of association with mucin synthesis.
AB  - BACKGROUND/AIMS: Postconfluence differentiation followed by a decrease in mucin
      synthesis has been described for the colonic adenocarcinoma cell line Caco-2.
      Because the onset of differentiation usually heralds the end of proliferation, we
      expected Caco-2 would be more tumorigenic in the exponential phase. Thus, we
      compared tumorigenicity, clonigenicity, and mucin synthesis in the exponential
      and stationary growth phases. METHODS: We estimated mucin synthesis in Caco-2
      cells by measuring the amount of high-molecular-weight [3H]glucosamine-labeled
      glycoprotein released into the culture medium and in the cytosolic fraction.
      Colony forming efficiency in soft agar and tumorigenicity in nude mice were
      assessed. RESULTS: Cells in the exponential phase synthesized significantly more
      mucin compared with stationary phase cells. Pretreatment with benzyl-GalNAc
      reduced production in both phases but did not change clonigenicity. Colonies did
      not grow from cells seeded in the exponential phase. The average weight of
      xenografts raised from postconfluence cells was twice that of xenografts raised
      from cells in the exponential phase. CONCLUSIONS: Neither exponential cell growth
      nor increased mucin production predicts clonigenicity and tumorigenicity. It is
      speculated that a stable process takes place in Caco-2 cells after confluence
      which makes them more clonigenic in vitro and enhances tumor growth in vivo.

PMID- 8299907
TI  - The endocytosis of transferrin by rat intestinal epithelial cells.
AB  - BACKGROUND/AIMS: The transferrin receptor is a prominent protein on the basal and
      lateral membranes of intestinal epithelial cells, yet little is known of the
      function of the receptor in the intestine. The aim of the present study was to
      determine whether intestinal transferrin receptors were capable of facilitating
      transferrin internalization. METHODS: Using the rat as an experimental model, the
      uptake of radiolabeled transferrin by cells isolated from different regions along
      the crypt-villus axis of the proximal small intestine was studied. RESULTS: An
      intestinal epithelial cell fraction highly enriched in crypt cells bound most
      radiolabeled transferrin. Cells in this fraction were able to internalize
      transferrin and recycle it back to the cell surface. A high affinity, saturable
      pathway of transferrin uptake by these cells predominated at transferrin
      concentrations below 0.3 mumol/L, whereas at higher concentrations, most uptake
      was via a nonsaturable process. Intravenously injected radiolabeled transferrin
      could be detected within intestinal crypt cells, indicating that these cells are
      able to internalize transferrin in vivo. CONCLUSIONS: These data suggest that
      intestinal crypt cells have an active transferrin/transferrin receptor system.
      Transferrin may play an important role in iron delivery to and/or as a growth
      factor for the rapidly proliferating intestinal epithelium.

PMID- 8299908
TI  - Kinetic studies on the metabolism of short-chain fatty acids and glucose by
      isolated rat colonocytes.
AB  - BACKGROUND/AIMS: Although the interest in colonic mucosal metabolism of short
      chain fatty acids is steadily increasing, the kinetic parameters Vmax (maximum
      velocity) and Km (Michaelis constant) of the complete oxidation of these acids
      into CO2 by colonic epithelial cells have not previously been determined.
      METHODS: Isolated rat colonocytes were incubated in the presence of a
      concentration range of 14C-labeled acetate, propionate, butyrate, and glucose.
      Oxidation rates were obtained by quantifying the production of 14CO2. Vmax and Km
      were calculated by computer-fitting of the data to a Michaelis-Menten plot.
      RESULTS: The apparent Vmax values were similar comparing acetate, propionate, and
      butyrate (1.114 +/- 0.061, 0.991 +/- 0.072, and 1.007 +/- 0.070 mumol/min.g,
      respectively), but significantly lower for glucose (0.339 +/- 0.022 mumol/min.g).
      The corresponding Km values were all different and in the order of butyrate
      (0.184 +/- 0.017 mmol/L) < propionate (0.339 +/- 0.025 mmol/L) < acetate (0.487
      +/- 0.019 mmol/L) < glucose (0.777 +/- 0.051 mmol/L). In substrate competition
      experiments, butyrate caused a strong noncompetitive inhibition of acetate
      oxidation and a mixed type of inhibition of propionate oxidation. Propionate
      inhibited the oxidation of acetate noncompetitively and that of butyrate
      competitively. Acetate only slightly inhibited the oxidation of propionate and
      butyrate. CONCLUSIONS: Colonic epithelial cells seem to utilize short-chain fatty
      acids in a preferential order of butyrate > propionate > acetate. Oxidation of
      propionate or acetate, however, may provide the energy needed for cellular
      functions if the metabolism of butyrate is impaired or the luminal supply is
      limited.

PMID- 8299909
TI  - Aflatoxin B1-adduct formation in rat and human small bowel enterocytes.
AB  - BACKGROUND/AIMS: Hepatic CYP3A enzymes have been implicated in the bioactivation
      of aflatoxin B1 (AFB1) to DNA binding metabolites. CYP3A enzymes are also
      abundant in the small bowel, and we therefore examined the ability of this tissue
      to form intracellular AFB1 adducts. METHODS: Immunohistochemistry using a
      antibody to the stable AFB1-DNA adduct was performed on small bowel sections
      obtained from rats orally gavaged with AFB1 and on human small bowel biopsy
      specimens maintained in explant culture. 3H-AFB1 was instilled into a loop of
      small bowel of untreated rats and rats pretreated with the CYP3A inducer
      dexamethasone during vivisection. DNA was isolated from the loop 2 hours later
      and assayed for specific activity. RESULTS: In both rats and humans, AFB1-adducts
      were detected exclusively in mature enterocytes in a pattern similar to the
      distribution of CYP3A enzymes. Induction of enterocyte CYP3A in rats resulted in
      an increase in enterocyte immunoreactive AFB1 adducts and in a 1.8-fold increase
      in 3H-AFB1-nucleic acid adducts (P = 0.01). CONCLUSIONS: Intracellular AFB1
      adducts are formed in the small intestine, and this reflects, at least in part,
      the catalytic activity of CYP3A enzymes. Because these AFB1 adducts should
      ultimately pass in stool, enterocyte CYP3A may represent a regulatable barrier to
      dietary aflatoxins.

PMID- 8299910
TI  - Hepatic injury and lethal shock in galactosamine-sensitized mice induced by the
      superantigen staphylococcal enterotoxin B.
AB  - BACKGROUND/AIMS: Staphylococcal enterotoxin B (SEB) acts as a superantigen
      binding to class II major histocompatibility complex proteins, and this complex
      stimulates T cells. The aim of this study was to investigate the pathogenic
      effects of SEB on hepatic injury and lethal shock in mice. METHODS: SEB was
      administered to D-galactosamine (GalN)-sensitized mice, and the degree of liver
      injury and levels of circulating cytokines were determined. In vitro cytokine
      production in response to SEB was also investigated. RESULTS: Intraperitoneal
      administration of SEB (50 micrograms) caused lethal shock (50% mortality)
      associated with massive hepatic necrosis in GalN-sensitized mice, with no
      mortality on injection of up to 100 micrograms SEB alone. Within 2 hours after
      injection of SEB, serum tumor necrosis factor alpha (TNF-alpha) levels reached a
      peak, followed by high levels of serum interferon-gamma (IFN-gamma) up to 10
      hours after injection. Passive immunization with anti-TNF-alpha/beta-neutralizing
      monoclonal antibody (mAb) protected GalN-sensitized mice from the lethal effects
      of SEB, with less protection with anti-IFN-gamma-neutralizing mAb. SEB induced
      the production of TNF-alpha and IFN-gamma in a dose-dependent manner from splenic
      mononuclear cells in vitro. CONCLUSIONS: The results show that SEB contributes to
      lethal shock associated with severe hepatic injury in GalN-sensitized mice and
      suggest that TNF-alpha and IFN-gamma produced in response to SEB may be mediators
      of the lethal toxicity and hepatotoxicity of SEB.

PMID- 8299911
TI  - Clinical aspects of incomplete septal cirrhosis in comparison with macronodular
      cirrhosis.
AB  - BACKGROUND/AIMS: Incomplete septal cirrhosis (ISC) is a form of macronodular
      cirrhosis characterized by slender, incomplete septa that demarcate inconspicuous
      nodules. Its clinical features have not been investigated in a large series. The
      aims of this study were to review the clinical symptoms and evolution of ISC in
      42 patients. METHODS: Forty-two patients with at least one liver biopsy strongly
      suggestive of ISC were selected for the study covering a period between 1968 and
      1987. Data for these patients were compared with the evolution of 49 patients
      with classical macronodular cirrhosis after chronic active hepatitis type B or C.
      RESULTS: Possible etiological factors for ISC were alcohol abuse, arsenic
      treatment, and hepatitis B infection. In three cases, a genetic factor could not
      be excluded. Patients with ISC had significantly lower serum concentrations of
      transaminases and bilirubin at diagnosis. Compared with macronodular cirrhosis,
      bleeding varices were more frequent (57% vs. 22%) in ISC. Ten-year survivals in
      the ISC and the macronodular cirrhosis groups were 54% and 57%, respectively.
      CONCLUSIONS: ISC represents a relatively stable burnt-out form of macronodular
      cirrhosis with an unusually high incidence of variceal bleeding. This could be
      explained by a superimposed insufficiency of the portal vascular supply.

PMID- 8299912
TI  - Hepatotoxicity of germander in mice.
AB  - BACKGROUND/AIMS: An epidemic of hepatitis due to germander teas or capsules
      recently occurred in France. The aim of the present study was to show the
      hepatotoxicity of germander and determine its mechanism in mice. METHODS: A
      germander tea lyophilisate and a fraction that isolated and concentrated 10-fold
      the furano neo-clerodane diterpenoids of the lyophilisate were prepared. RESULTS:
      (1) Intragastric administration of the lyophilisate (1.25 g/kg) or the furano neo
      clerodane diterpenoid fraction (0.125 mg/kg) produced similar midzonal liver cell
      necrosis at 24 hours in mice. (2) Toxicity was prevented by pretreatment with a
      single dose of troleandomycin (a specific inhibitor of cytochromes P4503A) and
      enhanced by pretreatment with dexamethasone or clotrimazole (two inducers of
      cytochromes P4503A). (3) Toxicity was attenuated by pretreatment with butylated
      hydroxyanisole or clofibrate (two inducers of microsomal epoxide hydrolase) and
      markedly increased by phorone-induced glutathione depletion. CONCLUSIONS: We
      conclude that germander constituents (probably its furano neo-clerodane
      diterpenoids) are transformed by cytochromes P450 (particularly P4503A) into
      hepatotoxic metabolites. The metabolites (probably epoxides) are partly
      inactivated by glutathione and probably epoxide hydrolase.

PMID- 8299913
TI  - Long-term ethanol feeding selectively impairs the attachment of rat perivenous
      hepatocytes to extracellular matrix substrates.
AB  - BACKGROUND/AIMS: We have previously shown that long-term ethanol consumption by
      rats results in a profound decrease in hepatocyte attachment to various
      extracellular matrix substrates. The present study investigated whether
      differences in attachment exist between cells isolated from either the periportal
      or perivenous regions of the liver. METHODS: Rats received long-term ethanol, and
      hepatocytes were selectively isolated by the digitonin-collagenase perfusion
      method. The ability of periportal and perivenous cells isolated from ethanol-fed
      and pair-fed control rats to attach to plates coated with either laminin,
      fibronectin, or type I collagen was then assayed. RESULTS: With all substrates,
      the attachment of perivenous hepatocytes isolated from ethanol-fed animals was
      significantly impaired. Time-course studies showed that although the rate of
      attachment of perivenous cells from ethanol-fed animals was only slightly
      reduced, a dramatic decrease in absolute attachment was observed. Furthermore,
      the perivenous cells isolated from ethanol-fed animals detached more readily from
      the substrate-coated plates than the corresponding periportal cells or either
      periportal or perivenous cells from pair-fed controls. CONCLUSIONS: Long-term
      ethanol consumption impairs hepatocyte-extracellular matrix interactions more
      severely in the perivenous region of the liver. This finding could be relevant to
      the pathological changes observed in alcoholic liver injury.

PMID- 8299914
TI  - Impairment of glucagon-induced hepatic system A activity by short-term ethanol
      administration in the rat.
AB  - BACKGROUND/AIMS: System A is a membrane-bound, hormonally regulated carrier of
      amino acids that is induced by liver regeneration and impaired by ethanol. The
      mechanism of ethanol inhibition of system A is unknown; this study examines the
      effects of ethanol on the subcellular expression of system A activity following
      hormonal induction. METHODS: Following hormonal treatment and short-term ethanol
      administration to rats, isolated liver Golgi and plasma membrane vesicles were
      examined for system A transport, and the kinetic parameters were determined.
      RESULTS: Four hours after ethanol administration, the initial rate of system A
      activity was depressed 30% +/- 9% and 19% +/- 7% into Golgi and plasma membrane
      vesicles, respectively. The affinity constant of 2-(methylamino)-isobutyric acid
      uptake was unchanged between control and ethanol-treated vesicles, regardless of
      their subcellular origin. However, the maximal velocity of system A transport
      decreased from 1030 to 850 pmol.mg-1 protein.10 s-1 in Golgi vesicles and from
      740 to 355 pmol.mg-1 protein.10 s-1 in plasma membrane vesicles. CONCLUSIONS:
      Ethanol impairs hormonally induced system A activity in Golgi as well as in the
      plasma membrane vesicles. Ethanol potentially reduces glucagon induction of
      system A activity through an impairment of carrier biosynthesis or expression.

PMID- 8299915
TI  - Is the plasma amino acid consumption test an accurate test of exocrine pancreatic
      insufficiency?
AB  - BACKGROUND/AIMS: The amino acid consumption test has been proposed as an accurate
      test of exocrine pancreatic function. The diagnostic accuracy of this test was
      determined by simultaneously measuring plasma amino acids and enzyme secretion
      during stimulation of the pancreas with cholecystokinin octapeptide (CCK-OP) in
      60 consecutive patients suspected of having pancreatic insufficiency. METHODS:
      All patients underwent duodenal intubation and intravenous infusion of CCK-OP (40
      ng.kg-1.h-1). Pancreatic enzyme (lipase and trypsin) outputs and plasma amino
      acids were measured for a period of 1 hour. Total and individual plasma amino
      acids were quantitated by ion-exchange chromatography. The severity of pancreatic
      insufficiency was graded on the basis of enzyme output during CCK-OP infusion.
      RESULTS: There was no relationship between pancreatic enzyme output and plasma
      concentrations of individual or total amino acids before or during CCK-OP
      stimulation. Using a total amino acid decrease of 12% as the cutoff, the amino
      acid consumption test was 91% sensitive, but very nonspecific (21% specificity)
      for detection of pancreatic insufficiency. CONCLUSIONS: The amino acid
      consumption test with CCK-OP stimulation does not discriminate between patients
      with normal and impaired exocrine pancreatic secretion.

PMID- 8299916
TI  - A double-blind controlled trial of oral-pulse methotrexate therapy in the
      treatment of primary sclerosing cholangitis.
AB  - BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is a progressive disease
      with no accepted effective treatment. Because methotrexate was associated with
      clinical and histological improvement in two men with PSC, we conducted a
      prospective trial of methotrexate in PSC. METHODS: A prospective placebo
      controlled, double-blind trial of methotrexate in PSC was performed. Twenty-four
      patients with PSC were randomized to receive methotrexate or placebo for a 2-year
      period. Seven of 12 taking methotrexate and five taking placebo had cirrhosis.
      Serial liver biopsies, endoscopic retrograde cholangiopancreatography (ERCP), and
      biochemical tests of liver function were followed. RESULTS: There were no
      significant changes in liver histological results, ERCP findings, tests of liver
      function (other than alkaline phosphatase), or outcome between the two groups.
      Mean alkaline phosphatase levels decreased by 152 IU in the methotrexate group
      and increased by 30 IU in the placebo group (P = 0.032). Patients taking
      methotrexate were more likely to reduce or discontinue cholestyramine than
      patients taking placebo. CONCLUSIONS: This study does not support efficacy for
      methotrexate in the treatment of PSC. On the basis of this study, the empiric use
      of methotrexate in patients with PSC is not recommended. However, methotrexate is
      being further evaluated in patients with precirrhotic PSC.

PMID- 8299917
TI  - Oral hairy leukoplakia in a patient with ulcerative colitis.
AB  - A 30-year-old man with ulcerative colitis developed oral hairy leukoplakia (OHL).
      Serological examination for human immunodeficiency virus (HIV)-1 and HIV-2
      infection showed no abnormalities. Biopsy specimen of the lateral tongue showed
      ballooned prickle cells, and electron microscopy revealed herpes-type viruses.
      Immunologic investigation of the patient showed a marked decrease in T-helper
      cells as a result of immunosuppressive regimen. The present report appears to be
      the first well-documented case of OHL in an HIV-negative patient with ulcerative
      colitis. OHL may be a marker for severe immunosuppression but is not necessarily
      associated with HIV infection. Patients with iatrogenic immunosuppression should
      be monitored for OHL. Concerning the marked decrease in T-helper cells in this
      case, the presence of OHL may imply the examination of T-lymphocyte subsets in
      patients such as HIV-infected individuals or in organ transplant recipients.

PMID- 8299918
TI  - Cytokines in intestinal inflammation: pathophysiological and clinical
      considerations.

PMID- 8299919
TI  - Enterocolitis associated with Shiga-like toxin production: an appropriate animal
      model at last?

PMID- 8299920
TI  - Endoscopic laser therapy for radiation-induced mucosal hemorrhage: have we seen
      the light?

PMID- 8299921
TI  - Should you be following carcinoembryonic antigen levels in your patients with
      colon cancer?

PMID- 8299922
TI  - Cell cycle abnormalities in Barrett's esophagus: further insights.

PMID- 8299923
TI  - Mesalazine as maintenance treatment in Crohn's disease.

PMID- 8299924
TI  - What constitutes compliance?

PMID- 8299925
TI  - Progression of primary biliary cirrhosis on ursodeoxycholic acid.

PMID- 8299926
TI  - Do changes in cell shape affect suspension conductivity?
AB  - The conductivity of a suspension containing uniformly oriented asymmetric cells
      depends on the shape of the cells. Whether the shape of cells with random spatial
      orientation also affects the conductivity of a suspension is not clear. A highly
      sensitive apparatus was used to register the dynamic changes in conductivity of
      erythrocyte suspension, upon induced morphological transformation discocytes<-
      >spherocytes). The results obtained with a sensitivity of up to 0.06% show that
      the drastic change of cell shape itself did not affect the suspension
      conductivity.

PMID- 8299927
TI  - Tris buffer protects DNA backbone against breakage upon irradiation with
      ultraviolet light.
AB  - We show that Tris molecules protect DNA against nicking upon irradiation with
      ultraviolet light. However, the protective effect only concerns DNA backbone but
      not bases and it is observed in aqueous solution but not in formamide. Changes of
      pH or ionic strength due to Tris have no effect on the protection. The present
      observation has a practical importance for photofootprinting studies of DNA and
      its complexes with proteins but it can also serve as a basis for a development of
      a novel method reflecting DNA hydration and conformation.

PMID- 8299928
TI  - Two types of Ca(2+)-channels in cells from the circular layer of guinea-pig
      ileum.
AB  - In this paper data are presented concerning some morphometrical characteristics
      and passive electrical properties of cell membranes from the circular layer of
      guinea-pig ileum (CC). The main purpose of the study has been to analyze the
      inward calcium current in these cells. Using the whole-cell voltage-clamp method
      the presence of T-like type of calcium channels (conducting low-threshold, fast
      inactivated, strictly potential-dependent and dihydropyridine-resistant calcium
      inward current--If) could be found in membranes of the cells investigated. The
      participation of If in the total inward current of CC was deduced from the
      presence of a low-threshold "hump" in the current-voltage relation curve (I/V
      curve) between -80 and -50 mV, and also from a negative shift of this curve at
      holding potential Vh = -90 mV, compared to the one obtained at Vh = -50 mV.
      Besides, in the presence of a dihydropyridine Ca2+ antagonist, a fast
      inactivating component of the inward current could be recorded, which was
      effectively blocked by 0.3 mmol/l Ni2+ from outside. According to Tsien's
      criteria (1983) our data suggest the coexistence of T- and L-types calcium
      channels in CC.

PMID- 8299929
TI  - Distribution of Ca(2+)-modulating proteins in sarcoplasmic reticulum membranes
      after denervation.
AB  - The early response to the loss of motor innervation to the muscle is connected
      with an altered Ca(2+)-homeostasis. Our study, based on Western blotting,
      indicates that denervation influenced expression of some sarcoplasmic Ca(2+)
      modulating proteins. Evidence has been brought for an increase of the level of
      calsequestrin and of the putative ryanodine receptor paralleled with a slight
      decrease of the total amount of Ca(2+)-pump protein. The expression of unchanged
      Ca(2+)-pump isoform and unaltered quantities of other non-junctional Ca(2+)
      binding proteins support the hypothesis that changed cellular Ca2+ homeostasis
      include also an alteration of Ca(2+)-modulating systems, mainly from the
      junctional region of sarcoplasmic membranes.

PMID- 8299930
TI  - Effects of nordihydroguaiaretic acid on the chemiluminescence of murine
      phagocytes.
AB  - Antioxidative effects of nordihydroguaiaretic acid (NDGA) on murine bone marrow
      phagocytes were studied using luminol- and lucigenin-amplified chemiluminescence
      (CL). NDGA applied in vitro strongly suppressed the opsonized zymosan particles
      stimulated CL response in a dose-dependent manner (in concentrations of 0.3-30
      micrograms NDGA/ml), thus confirming its antioxidant activity. However, no
      effects were observed in mice and their serum samples when investigated one
      minute to one hour after an i.p. administration of NDGA. These differences
      suggest that NDGA may undergo a rapid metabolism in vivo.

PMID- 8299931
TI  - Interaction of [2-(alkyloxy)-phenyl]-2-(1-piperidinyl)ethyl esters of carbamic
      acid with dipalmitoylphosphatidylglycerol model membranes: a calorimetric study.
AB  - As detected by adiabatic differential scanning microcalorimetry, [2-(alkyloxy)
      phenyl]-2-(1-piperidinyl)ethyl esters of carbamic acid (CnPPEECA, n is the number
      of carbon atoms in the alkyloxy substituent) with local anesthetic and
      antiarrhythmic activities interact with 1,2-dipalmitoyl-sn-glycero-3-[phosphorac
      (1-glycerol)] model membranes (DPPG). CnPPEECAs form solid-like solutions with
      DPPG at low CnPPEECA concentrations and with short alkyloxy chain lengths (n <
      4), while at higher concentrations and with longer alkyloxy chains (10 > or = n >
      or = 5) demixing and separation of CnPPEECA+DPPG clusters of unknown
      stoichiometry occurs in the gel phase. The temperature of the gel-liquid crystal
      phase transition Tm is depressed in the presence of CnPPEECA; the depression of
      Tm scaled for unity CnPPEECA concentration in the lipid phase indicates higher
      intrinsic perturbation activity of the charged form of CnPPEECA than that of the
      basic form of CnPPEECA. It is suggested that this might be caused by a deeper
      location of the basic form of CnPPEECA in the lipid bilayer.

PMID- 8299932
TI  - Radiation damage to lymphocyte membrane. Changes of binding and fluorescent
      parameters of 1-anilino-8-naphthalene sulphonate.
AB  - The changes of binding and fluorescent parameters of 1-anilino-8-naphthalene
      sulphonate (ANS) bound to lymphocyte membrane after irradiation in vitro were
      investigated. No significant dose dependence was found for either fluorescence or
      its polarization within the dose range of 0.1 to 0.7 Gy from a gamma-neutron
      field 252Cf source. Marked changes were however found for parameters of ANS
      binding to membrane after irradiation. The number of binding sites decreased by
      about 60% and the dissociation constant K decreased by about 70% as compared to
      control values. The quantum yield of fluorescence also decreased compared with
      control value. The experimental findings were interpreted as suggesting
      structural changes in the lipid environment of the lymphocyte membrane caused by
      irradiation.

PMID- 8299933
TI  - Model of intracellular calcium oscillations activated by inositol trisphosphate.
AB  - Transients or oscillations of intracellular free calcium concentration are
      general means for physiological intracellular signalling. Recently, it was shown
      that calcium ions modulate the InsP3 receptor/releasing calcium channel of the
      endoplasmic reticulum in a concentration dependent manner. Calcium either
      enhances (at low concentrations) or decreases (at high concentrations) the
      permeability of the channel activated by InsP3. A simple phenomenological model
      is proposed, based on these data. The model consists of two compartments. They
      are the cytoplasm and the endoplasmic reticulum with the calcium sequestering
      pump and the calcium release channel activated by InsP3. Parameters of the model
      are related to the experimentally measurable quantities. A qualitative analysis
      has shown that the hypothesis, which includes calcium modulation of the calcium
      releasing channel activated by InsP3, can explain all essential experimental
      findings. At least in cells with predominating calcium compartments with InsP3
      sensitivity, this type of channel is compatible with mechanisms which generate
      repetitive calcium transients.

PMID- 8299934
TI  - The TGF-beta superfamily: new members, new receptors, and new genetic tests of
      function in different organisms.

PMID- 8299935
TI  - Suppression of activated Let-60 ras protein defines a role of Caenorhabditis
      elegans Sur-1 MAP kinase in vulval differentiation.
AB  - The let-60 ras gene of Caenorhabditis elegans is one of the key players in a
      signal transduction pathway that controls the choice between vulval and epidermal
      differentiation in response to extracellular signals. To identify components
      acting downstream of let-60 ras in the vulval signaling pathway, we have
      identified a reduction-of-function mutation in the sur-1 gene that completely
      suppresses the multivulva phenotype of a hyperactive let-60 ras mutation. About
      10% of animals homozygous for the sur-1 mutation also display a specific and
      intriguing vulval cell lineage defect. In addition, the sur-1 mutation results in
      a cold-sensitive egg-laying defective phenotype and a partial larval lethal
      phenotype. We have cloned the sur-1 gene by DNA-mediated transformation and have
      shown that it encodes a protein similar in overall structure to mammalian MAP
      kinases (ERKs). The functional homology between Sur-1 MAP kinase and mammalian
      MAP kinases was also demonstrated by the ability of a rat ERK2 kinase to rescue
      the sur-1 mutant phenotypes. Genetic double-mutant analyses place sur-1
      downstream of let-60 ras but upstream of lin-1 in the vulval signaling pathway.
      Our results provide further evidence for the extreme conservation of Ras-mediated
      signaling pathway between worms and humans and for the function of MAP kinases in
      cell signaling processes that control cell differentiation and animal
      development.

PMID- 8299936
TI  - A MAP kinase homolog, mpk-1, is involved in ras-mediated induction of vulval cell
      fates in Caenorhabditis elegans.
AB  - During development of the Caenorhabditis elegans hermaphrodite, the gonadal
      anchor cell induces nearby Pn.p cells to adopt vulval fates. The response to this
      signal is mediated by a receptor tyrosine kinase signal transduction pathway that
      has been remarkably well conserved during metazoan evolution. Because mitogen
      activated protein (MAP) kinases are activated by receptor tyrosine kinase
      pathways in vertebrate cells, we hypothesized that C. elegans MAP kinase homologs
      may play a role in vulval induction. Two C. elegans MAP kinase genes, mpk-1 and
      mpk-2 (mpk, MAP kinase), were cloned using degenerate oligonucleotide primers and
      PCR amplification; in parallel, genes involved in vulval induction were
      identified by screening for mutations that suppress the vulval defects caused by
      an activated let-60 ras gene. One such suppressor mutation is an allele of mpk-1.
      We used a new type of mosaic analysis to show that mpk-1 acts cell autonomously
      in the Pn.p cells. Our results show that mpk-1 plays an important functional role
      as an activator in ras-mediated cell signaling in vivo.

PMID- 8299937
TI  - Wnt-3a regulates somite and tailbud formation in the mouse embryo.
AB  - Amphibian studies have implicated Wnt signaling in the regulation of mesoderm
      formation, although direct evidence is lacking. We have characterized the
      expression of 12 mammalian Wnt-genes, identifying three that are expressed during
      gastrulation. Only one of these, Wnt-3a, is expressed extensively in cells fated
      to give rise to embryonic mesoderm, at egg cylinder stages. A likely null allele
      of Wnt-3a was generated by gene targeting. All Wnt-3a-/Wnt-3a- embryos lack
      caudal somites, have a disrupted notochord, and fail to form a tailbud. Thus, Wnt
      3a may regulate dorsal (somitic) mesoderm fate and is required, by late primitive
      steak stages, for generation of all new embryonic mesoderm. Wnt-3a is also
      expressed in the dorsal CNS. Mutant embryos show CNS dysmorphology and ectopic
      expression of a dorsal CNS marker. We suggest that dysmorphology is secondary to
      the mesodermal and axial defects and that dorsal patterning of the CNS may be
      regulated by inductive signals arising from surface ectoderm.

PMID- 8299938
TI  - Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53.
AB  - Many DNA tumor viruses express a protein that inhibits transcriptional activation
      by the tumor-suppressing transcription factor p53. We report that adenovirus E1B
      55K represses p53-mediated activation by a mechanism not described previously.
      E1B 55K binds p53 without displacing it from its DNA-binding site. A fusion of
      E1B 55K to the GAL4 DNA-binding domain represses transcription from a variety of
      promoters with engineered upstream GAL4-binding sites. Mutations within E1B 55K
      that interfere with its transforming activity and its ability to inhibit p53
      mediated trans-activation also interfere with transcriptional repression by the
      GAL4-55K fusion. These results demonstrate that E1B 55K functions as a direct
      transcriptional repressor that is targeted to p53-responsive genes by binding to
      p53.

PMID- 8299939
TI  - Region-specific activators of meiotic recombination in Schizosaccharomyces pombe.
AB  - Schizosaccharomyces pombe rec mutants were previously isolated on the basis of
      their deficiency in meiotic recombination at the ade6 locus. We surveyed their
      meiotic recombination deficiencies at and between other loci. In rec10 mutants
      recombinant frequencies in the approximately 2-Mb region surrounding the ade6
      locus were reduced 10- to 100-fold, but recombinant frequencies at or between
      nine other unlinked loci were reduced < 3-fold. The rec10 mutations are recessive
      and are on chromosome I; the ade6 region is on chromosome III. These results
      indicate that the rec10 gene product is required for activation of meiotic
      recombination in the approximately 2-Mb region surrounding ade6 but not in the
      other regions surveyed. Similar ade6 regional specificities were observed for
      rec8 and rec11. We infer that there are multiple activators of meiotic
      recombination, each specific for a limited set of loci, and we discuss how these
      regional activators may work.

PMID- 8299940
TI  - Regulation of splicing at an intermediate step in the formation of the
      spliceosome.
AB  - In vivo experiments have demonstrated that the ribosomal protein L32 of
      Saccharomyces cerevisiae brings about the inhibition of splicing of the
      transcript of its own gene through an RNA structure comprised largely of the
      first exon. We now show that L32, itself, binds specifically to this RNA.
      Splicing of the RPL32 transcript in vitro is blocked by the presence of L32.
      Furthermore, addition of the 75-nucleotide RNA representing the 5' end of the
      RPL32 transcript stimulates specifically the splicing of the RPL32 substrate,
      presumably by competing for L32 present in the extract. Use of RNAs carrying
      mutations shown to abolish the regulation of splicing, either as substrates or as
      competitors, confirmed that the in vitro reaction is a faithful representation of
      the situation in vivo. We conclude that the regulation of splicing occurs through
      the specific binding of L32 to an RNA structure within the first 75 nucleotides
      of the RPL32 transcript. The RPL32 substrate, bound to L32, forms a complex with
      U1 snRNP, the first step in spliceosome assembly. The presence of L32 prevents
      the ATP-dependent association of the U2 snRNP necessary to form a complete
      spliceosome.

PMID- 8299941
TI  - A stem/loop in U6 RNA defines a conformational switch required for pre-mRNA
      splicing.
AB  - U6 small nuclear RNA (snRNA) is an essential component of the spliceosome, the
      ribonucleoprotein complex that carries out the splicing of pre-mRNAs. The precise
      function of U6 RNA is unknown, but it has been proposed to participate directly
      in catalysis of the splicing reaction. We present biochemical and genetic
      evidence for an intramolecular stem/loop structure in the 3' half of U6 RNA of
      the yeast Saccharomyces cerevisiae that is mutually exclusive with the
      intermolecular base-pairing between U6 RNA and U4 snRNA. Strains with mutations
      that stabilize the U6 RNA 3'-intramolecular stem exhibit cold-sensitive growth
      and accumulate free U4 RNA, indicative of a block in U4/U6 snRNP assembly. The
      cold sensitivity can be partially suppressed by overexpression of U4 RNA.
      Mutations that disrupt base-pairing in the intramolecular 3' stem and mutations
      elsewhere in U6 RNA also suppress the growth defect. We conclude that a large
      conformational switch, involving melting of the U6 RNA 3' stem, is required for
      U4/U6 snRNP assembly. We hypothesize that formation of the U6 RNA intramolecular
      3' stem after U4 RNA leaves the assembled spliceosome serves to activate U6 RNA
      for splicing by juxtaposing regions in U6 RNA that interact with U2 small nuclear
      RNA.

PMID- 8299942
TI  - Subcellular localization of proteins involved in the assembly of the spore coat
      of Bacillus subtilis.
AB  - Spores of the bacterium Bacillus subtilis are encased in a two-layered protein
      shell, which consists of an electron-translucent, lamellar inner coat, and an
      electron-dense outer coat. The coat protein CotE is both a structural component
      of the coat and a morphogenetic protein that is required for the assembly of the
      outer coat. We now show that CotE is located in the outer coat of the mature
      spore and that at an intermediate stage of sporulation, when the developing spore
      (the forespore) is present as a free protoplast within the sporangium, CotE is
      localized in a ring that surrounds the forespore but is separated from it by a
      small gap. We propose that the ring is the site of assembly of the outer coat and
      that the gap is the site of formation of the inner coat. Assembly of the ring
      depends on the sporulation protein SpoIVA, which sits close to or on the surface
      of the outer membrane that encircles the forespore. We propose that SpoIVA
      creates a basement layer around the forespore on which coat assembly takes place.
      The subcellular localization and assembly of CotE and other coat proteins are
      therefore determined by the capacity of SpoIVA to recognize and adhere to a
      specific surface within the sporangium, the outer membrane of the forespore.

PMID- 8299943
TI  - A rapid and sensitive PCR strategy employed for amplification and sequencing of
      porA from a single colony-forming unit of Neisseria meningitidis.
AB  - The predicted amino acid sequence was determined for the class-1 outer membrane
      protein, PorA, from a B:15:P1.7,3 strain of Neisseria meningitidis that is
      currently causing an epidemic of meningitis in Northern Chile. The P1.7,3 PorA
      showed a unique sequence in the exposed loop 4 of the putative porin structure
      that is different from all the reported PorA sequences. Based on the nucleotide
      (nt) sequence of the P1.7,3 porA, we designed two sets of PCR (polymerase chain
      reaction) primers that specifically amplified porA from any N. meningitidis
      strain, and a third set of primers that amplified porA only from the P1.7,3
      strain. Using these primers, we developed a sensitive double hot-start nested PCR
      (HNPCR) strategy that could amplify porA and generate nt sequence from as low as
      a single colony-forming unit. This strategy consisted of three phases of PCR. The
      first two phases were designed to generate amplified target DNA that could be
      directly visualized by ethidium bromide staining starting from one to two
      molecules of Neisseria genome. The third phase was designed to generate a
      sequence of several hundred nt directly from the amplified DNA. A number of
      culture-negative cerebrospinal fluid samples from individuals suspected of
      meningitis during a vaccine trial were analyzed by this strategy to obtain more
      accurate information on the actual number of cases that occurred in the study and
      the non-study populations. The basic HNPCR strategy described here could be
      applied to amplify and sequence target DNAs from any low-copy-number biological
      sample.

PMID- 8299944
TI  - Novel lacZ-based recombination vectors for mammalian cells.
AB  - We have constructed two sets of Escherichia coli lacZ-based vectors for use in
      studies of general mitotic recombination, both in somatic mammalian cells grown
      in culture and in transgenic animals. The vectors use two mutant copies of the E.
      coli lacZ gene as their recombination substrates and contain a neo gene for
      selection of stable transformants. In one vector, pLrec, an SV40 promoter drives
      lacZ, while the other vector, pArec, utilizes a human non-muscle beta-actin
      promoter for lacZ expression. Gene conversions, unequal sister chromatid
      exchanges and reciprocal exchanges between the two lacZ genes result in
      expression of beta-galactosidase, which can be detected in situ by histochemical
      staining. These vectors yield rates and frequencies of mitotic intrachromosomal
      recombination in human and rodent cell lines which are similar to rates reported
      using conventional recombination vectors. Molecular analysis of recombinational
      events involving the lacZ-based vectors can be carried out on genomic DNA
      isolated from clonally expanded populations and individual LacZ+ cells and cell
      clusters can be analyzed using PCR amplification. These reporter gene-based
      vectors may facilitate the study of recombination in cells with limited
      proliferative capacities, allow for analysis of both products of an unequal
      sister chromatid exchange, and permit in situ detection of recombination in the
      tissues of transgenic animals.

PMID- 8299945
TI  - Cloning of the dihydroxyacid dehydratase-encoding gene (ILV3) from Saccharomyces
      cerevisiae.
AB  - The biosynthesis of branched-chain amino acids (aa) involves three shared
      pathways through which pyruvate or alpha-ketobutyrate are converted into alpha
      keto acids, precursors of valine, leucine or isoleucine. In eukaryotes, few of
      these common enzymes have been purified to homogeneity, and the whole complement
      of biosynthetic genes has not been cloned from a single species. In yeasts, most
      of these genes (ILV genes) have been cloned and sequenced, with the exception of
      that coding for dihydroxyacid dehydratase (DAD, EC 4.2.1.9), the third enzyme in
      the common pathways. We have isolated Saccharomyces cerevisiae genomic sequences
      by hybridization to an oligodeoxyribonucleotide (oligo) probe designed from a
      highly conserved domain among bacterial DAD-encoding genes. The cloned sequences
      have been located to S. cerevisiae chromosome X, mapped within 0.4 centiMorgans
      (cM) of the ilv3 locus, and found to complement the ilv3 mutations of various
      yeast strains. Nucleotide (nt) and aa sequence analyses of the longest open
      reading frame (ORF) located within the cloned sequences identified them as the
      ILV3 gene, which codes for the yeast DAD. With our cloning of ILV3, yeast becomes
      the only eukaryotic system from which all ILV genes have been cloned, thus
      allowing direct molecular analyses of their regulation.

PMID- 8299946
TI  - The gamma-tubulin-encoding gene from the basidiomycete fungus, Ustilago violacea,
      has a long 5'-untranslated region.
AB  - The gene (gamma-tub) encoding gamma-tubulin (gamma-Tub) was isolated from a
      cosmid library constructed for Ustilago violacea by using a PCR-amplified DNA
      fragment as a probe. About 2.8 kb of DNA sequence was analyzed and found to
      encode a protein of 469 amino acids highly homologous to the gamma-Tub from other
      organisms. There were eight introns interrupting the coding sequence. A 'TATA'
      like sequence was found 389 bp upstream from the initial Met codon. No
      polyadenylation signal was found in the 3' non-coding region. Southern blot
      analyses indicated that gamma-tub is a single-copy gene. Northern blot analyses
      indicated that a 1.81-kb RNA species was transcribed. Primer extension
      experiments determined that the transcription start point (tsp) is at 58 bp
      downstream from the putative TATA box, with another possible tsp at 95 bp
      downstream. The long 5' non-coding sequence of the RNA contained several small
      open reading frames; their possible roles in the regulation of gamma-tub
      translation are discussed.

PMID- 8299947
TI  - Mouse cDNAs encoding a trifunctional protein of de novo purine synthesis and a
      related single-domain glycinamide ribonucleotide synthetase.
AB  - Three of the enzymatic activities of de novo purine synthesis, glycinamide
      ribonucleotide synthetase (GARS), aminoimidazole ribonucleotide synthetase (AIRS)
      and glycinamide ribonucleotide formyltransferase (GART), can be catalyzed by a
      single 110-kDa protein in mouse cells. Western blots using a polyclonal antibody
      (Ab) to this protein identified two species, the trifunctional 110-kDa protein
      and a 50-kDa cytosolic protein with GARS, but not GART activity. We used Ab and,
      subsequently, oligodeoxyribonucleotide screens to isolate cDNAs corresponding to
      these two proteins from mouse T-cell cDNA expression libraries. The sequence of
      one class of these cDNAs and the partial sequence of a corresponding genomic
      clone defined an open reading frame (ORF) encoding a 1010-amino-acid (aa)
      protein, individual domains of which showed high homology to each of the
      monofunctional bacterial GARS, AIRS and GART proteins, and to each domain of
      chicken and human trifunctional GARS-AIRS-GARTs. cDNAs corresponding to the
      smaller protein contained a 1.3-kb ORF with complete identity to the GARS domain
      of, but with a 3' untranslated region different from, the trifunctional cDNAs.
      Hence, both cDNAs appear to derive from the same gene due to either differential
      splicing or use of an intronic polyadenylation signal. The functional requirement
      for the expression of both trifunctional protein with GARS activity and
      monofunctional, catalytically active GARS is unknown.

PMID- 8299948
TI  - The 3' flanking region of the human erythropoietin-encoding gene contains
      nitrogen-regulatory/oxygen-sensing consensus sequences and tissue-specific
      transcriptional regulatory elements.
AB  - We have reported the identification of a classical canonical CAAT box, TATA boxes
      and other transcriptional regulatory elements in the 5' flanking region of the
      human erythropoietin (hEp)-encoding gene [Lee-Huang et al., Gene 128 (1993) 227
      236]. These elements were not found in the hEp genomic clones reported by others.
      Our genomic clone extends in both directions beyond any reported clones, by 3.9
      kb on the 5' side and by 1.8 kb on the 3' side. Many important regulatory
      elements are found in these extended flanking regions. We report here the genomic
      structure of the extended 3' flanking region of hEp. This region contains the
      following regulatory elements: nitrogen-regulatory/oxygen-sensing consensus
      sequences, 5'-TTTTGCA and 5'-CCCTGCA; tissue-specific regulatory elements,
      including binding sites for A-activator, 5'-GTGGTGCAA; for DBP, 5'-TGATTTTGT; for
      HNF, 5'-T(A/G)TTTGT; and for C/EBP, 5'-T(T/G) (T/G)TGCAAT; a lymphokine
      responsive element, 5'-GTGAAACCCC (Rev), as well as binding sites for AP and Sp1.
      In addition, the nucleotide (nt) sequence in this region is rich in inverted
      repeats (palindromes) that allow the formation of hairpin loops. A total of 14
      potential stem loops with a maximum loop size of 20 nt are found. The
      identification of these regulatory elements in hEp should provide further insight
      into the tissue-specific and inducible expression of hEp. Such knowledge should
      be useful in the clinical modulation of erythropoiesis under physiologic and
      pathologic conditions.

PMID- 8299949
TI  - Construction and characterization of new host-vector systems for the enforcement
      cloning method.
AB  - The Escherichia coli host strains, TH1, TH2, TH3 alpha, TH4 and TH5, all trpR-,
      rpsL- and supE-, were constructed to constitutively express a trp
      promoter/operator (POtrp)-driven synthetic rpsLam+ gene encoding the streptomycin
      sensitivity (Sms) determinant (ribosomal protein S12). The applicability of these
      strains to the Sms-enforcement cloning procedure [Toba-Minowa and Hashimoto
      Gotoh, Gene 121 (1992) 25-33] was examined on tryptophan-rich low-salt (LS) agar
      medium in combination with two reconstructed Sms-enforcement plasmid vectors,
      ampicillin-resistant (ApR) pKF2, and chloramphenicol-resistant (CmR) pKF3. The
      results indicated that (1) pKF2 enforced the Sms phenotype on TH1, TH2, TH4 and
      TH5, but not TH3 alpha, while pKF3 was effective on all the strains, (2) even
      without Sm, strains TH1, TH2, TH4 and TH5 harboring pKF2 rarely formed colonies
      on LS+Ap agar, and (3) TH2 harboring pKF3 hardly grew, forming tiny colonies only
      after two overnight incubations at 37 degrees C on LS+Cm agar. By using the AseI,
      BclI, StuI and EcoRI sites in POtrp-rpsL+4am of pKF2 and pKF3, it was revealed
      that enforcement cloning was applicable in the new host-vector systems on normal
      nutrient agar medium, except for a combination of TH3 alpha and pKF2, with the
      TH2 strain in combination with pKF2 or pKF3 seeming to be most suitable for
      enforcement cloning, even without Sm.

PMID- 8299950
TI  - Construction of Tn4001lac derivatives to be used as promoter probe vectors in
      mycoplasmas.
AB  - Studies of gene expression in mycoplasmas has been difficult, because the
      elements involved in gene expression remain relatively undefined. In order to be
      able to examine these regulatory elements in vivo, derivatives of Tn4001
      containing the promoterless Escherichia coli lacZ reporter gene have been
      constructed. A Tn4001lac derivative, Tn4001.2062.2lac, transforms Mycoplasma
      gallisepticum and Acholeplasma strain ISM1499. Approximately 3% of the M.
      gallisepticum and 8% of the Acholeplasma ISM1499 transformants appeared to
      generate lacZ fusions based on blue colony formation on XGal-containing media.
      However, placement of lacZ into an IS256 arm of Tn4001 resulted in a derivative
      that transformed at a frequency about 3-7-fold lower than that of wild-type
      Tn4001. Another Tn4001lac derivative, Tn4001.2065, possesses a plasmid, as well
      as lacZ, in the IS256 arm. This construct was designed to permit the direct
      rescue of adjacent chromosomal sequences that are driving the expression of lacZ
      contained within the transposon. These constructs should be useful in locating
      and defining the upstream elements involved in mycoplasma gene expression.

PMID- 8299951
TI  - Construction of glucose-repressible yeast expression vectors.
AB  - A set of two episomal yeast expression vectors, pYME1 and pYME2, were
      constructed. These Saccharomyces cerevisiae-Escherichia coli shuttle vectors each
      contain a modified yeast MAL6S (encoding maltase) promoter that is expressed
      constitutively, but is subject to carbon catabolite repression by glucose.
      Expression from this promoter is still dependent upon the presence of active MALR
      (regulatory) protein. These expression vectors are particularly useful because
      most S. cerevisiae strains are MAL+, thereby exhibiting a wider host range than
      GAL-based vector systems. These pYME1 and pYME2 vectors are capable of expression
      to levels comparable to GAL-based expression plasmids and much higher than a
      variety of other repressible promoter vectors. The vectors are identical, except
      that their multiple cloning sites (MCS) are in opposite orientations, making them
      convenient for inserting heterologous genes.

PMID- 8299952
TI  - High- and low-copy-number Lactococcus shuttle cloning vectors with features for
      clone screening.
AB  - High- and low-copy-number shuttle cloning vectors were constructed by
      incorporating the Escherichia coli P15A plasmid origin of replication into the
      pAM beta 1-derived vectors, pIL252 and pIL253. The resulting vectors were
      structurally stable in Lactococcus, which is a common feature of theta
      replicating plasmids, and also displayed good structural stability in E. coli,
      possibly due to lack of a resolvase-encoding gene. All the vectors expressed
      erythromycin resistance (ErR) in both; brain heart infusion medium allowed clear
      selection of ErR in E. coli. Some of the vectors provided insertional
      inactivation of a cat (pTRKH1; pTRKL1) or tet (pTRKH1; pTRKH3; pTRKH5) gene to
      facilitate screening for clones. Multiple cloning sites in a lacZ gene, which
      expresses beta-galactosidase in lacZ alpha-complementing E. coli strains, were
      included in some vectors (pTRKH2/H5 and pTRKL2) to enable blue/white screening of
      clones on XGal plates. The 'H' and 'L' prefixes signify if the vector exists at
      high (H) or low (L) copy number in Lactococcus. Successful introduction of these
      vectors into Lactococcus, Enterococcus, Streptococcus and Lactobacillus
      highlights their utility for expanding the possibilities for genetic manipulation
      of these industrially significant bacteria.

PMID- 8299953
TI  - Transcriptional control of gonococcal pilE expression: involvement of an
      alternate sigma factor.
AB  - The pilE gene encoding Neisseria gonorrhoeae (Gc) pilin contains two putative
      promoter sequences 5' to the transcription start point (tsp), a Pribnow box and
      an RpoN-binding consensus sequence. Sequence analysis shows that the nucleotide
      (nt) sequence of the pilE promoter region is completely conserved among eight
      different Gc isolates. Using a pilE::lacZ transcriptional fusion, we demonstrate
      that the RpoN sigma factor can function in Escherichia coli to increase pilE
      transcription when the NifA activator from Klebsiella is present in trans. In
      addition, over-production of the native pilin protein using RpoN and NifA is
      lethal to E. coli. Finally, we show that the RpoN sigma factor decreases the
      basal expression of pilE when an activator is not present. These results suggest
      that, in Gc, pilE transcription may be regulated by RpoN in conjunction with an
      activator and that sigma 70 can also act to direct transcription of pilE.

PMID- 8299954
TI  - Bacillus subtilis flagellar proteins FliP, FliQ, FliR and FlhB are related to
      Shigella flexneri virulence factors.
AB  - The amino acid sequences of the Bacillus subtilis flagellar proteins, FliP, FliQ,
      FliR and FlhB, as deduced from their respective nucleotide sequences, were found
      to share significant homology to the Shigella flexneri Spa24, Spa9, Spa29 and
      Spa40 virulence proteins, respectively. These proteins are required for the
      presentation of surface plasmid antigens. These results further support the
      growing hypothesis that a superfamily of proteins exists for the biosynthesis of
      supramolecular structures that lie in an external to the cell membrane.

PMID- 8299955
TI  - Identification of a promoter for the crystal protein-encoding gene cryIVB from
      Bacillus thuringiensis subsp. israelensis.
AB  - The cryIVB gene of Bacillus thuringiensis subsp. israelensis (Bti) codes for a
      135-kDa insecticidal crystal protein, which is specifically toxic to dipteran
      larvae. We have identified a transcription start point (tsp) of cryIVB by a
      primer extension experiment. The promoter sequence alignment, together with the
      chronology of appearance of the transcript, suggested that cryIVB is transcribed
      by RNA polymerase containing sigma 35 (E sigma 35). This was confirmed by
      investigation of cryIVB transcription in several Bacillus subtilis sporulation
      mutants. Unlike the lepidopteran-specific crystal protein-encoding genes
      [cryIA(a) and cryIB], transcription of which is regulated by both sigma 35 and
      sigma 28, cryIVB transcription was controlled only by the sigma 35-dependent
      promoter at the midsporulation stage.

PMID- 8299956
TI  - Cloning, sequence and expression of the gene (aprV5) encoding extracellular
      serine acidic protease V5 from Dichelobacter nodosus.
AB  - The acidic protease V5-encoding gene (aprV5) from Gram- Dichelobacter nodosus
      virulent strain 198 was isolated from a cosmid bank by activity screening and
      sequenced. The 2371-bp nucleotide (nt) sequence contained an open reading frame
      coding for a protein precursor of 595 amino acid (aa) residues composed of a
      signal peptide, a pro-region, a mature active protease of 347 aa and a C-terminal
      extension region of 120 aa. The deduced aa sequence of the pre-pro-mature
      protease regions showed about 65% similarity to that of D. nodosus basic protease
      while the C-terminal extension region showed only about 26% similarity. The aprV5
      gene, without its C-terminal extension region, was cloned and expressed in
      Escherichia coli. The acidic protease B5-encoding gene (aprB5) from non-virulent
      strain 305 was also cloned and sequenced. The aprB5 nt sequence showed 99%
      homology to that of aprV5 with two single-aa changes occurring in the precursor.

PMID- 8299957
TI  - Isolation and nucleotide sequences of the genes encoding killer toxins from
      Hansenula mrakii and H. saturnus.
AB  - The HMK gene, encoding a killer toxin (HMK) of Hansenula mrakii strain IFO 0895,
      and the HSK gene, encoding a killer toxin (HSK) of H. saturnus strain IFO 0117,
      were cloned and sequenced. The HMK and HSK genes encode precursors to killer
      toxins of 125 amino acids (aa) and 124 aa, respectively. Both precursors have an
      N-terminal signal sequence of 37 aa which may be removed by a signal peptidase,
      and a propeptide which may be cleaved off by a KEX2-like protease. There is
      extensive homology between the aa sequences of HMK and HSK with the exception of
      the addition of one aa residue in HMK. The HMK and HSK genes were placed,
      separately, downstream from the yeast GAL10 promoter and introduced into a mutant
      of Saccharomyces cerevisiae that was resistant to the HMK. The transformants were
      capable of killing sensitive yeasts in medium that contained galactose with
      killing spectra similar to those of the donor strains of the toxins. These
      observations suggest that both killer toxins were synthesized and secreted from
      S. cerevisiae cells and killed sensitive yeasts, perhaps by the same mechanism as
      that associated with the donor strains and, moreover, that the difference in
      primary structure between the two toxins is responsible for the difference in
      their killing spectra.

PMID- 8299958
TI  - The gene family encoding the ribulose-(1,5)-bisphosphate carboxylase/oxygenase
      (Rubisco) small subunit of potato.
AB  - We determined the nucleotide sequences of five members of the rbcS gene family
      encoding the small subunit (SSU) of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) of potato. The genomic organization, structure
      and expression of the genes is compared to the features of the rbcS genes in
      tomato. Within the two species, Lycopersicon esculentum and Solanum tuberosum,
      both members of the Solanaceae, the rbcS genes share more interspecific sequence
      identity, especially in the 5'- and 3'-untranslated regions and the intron
      sequences, than within one species. However, the expression data of orthologous
      rbcS genes containing highly identical regulatory cis-acting elements were found
      to be different, suggesting that the simple finding of these motifs does not
      automatically imply similar transcriptional and/or post-transcriptional gene
      regulation.

PMID- 8299959
TI  - The 1629-bp open reading frame of the Autographa californica multinucleocapsid
      nuclear polyhedrosis virus encodes a virion structural protein.
AB  - A 1629-bp open reading frame (ORF) of Autographa californica multinucleocapsid
      nuclear polyhedrosis virus (AcMNPV) is shown to encode a 78-kDa virion structural
      protein. To determine this, polyclonal antibody was made to a fusion protein
      synthesized in Escherichia coli from a chimeric gene that contained 1415 bp of
      the 1629-bp gene. In Western blot analyses, this antibody cross-reacted with a
      protein of about 78 kDa in both extracellular virions (ECV) and virions isolated
      from polyhedra (PDV), and with a 78-kDa protein in PDV envelope preparations, but
      not with PDV nucleocapsids. This suggests that the protein encoded by the 1629-bp
      ORF is a virion envelope protein or a protein that occurs in the virion
      intermediate layer between the envelope and nucleocapsid.

PMID- 8299960
TI  - Identification, sequence and expression patterns of the Caenorhabditis elegans
      col-36 and col-40 collagen-encoding genes.
AB  - The collagen (Col)-encoding gene family in the nematode, Caenorhabditis elegans,
      consists of 50-150 members. We have undertaken studies of these genes as part of
      the analysis of the assembly of the cuticle, the nematode's exoskeleton. We
      present here the complete nucleotide and deduced amino acid sequences of the col
      36 and col-40 genes, both located on chromosome II and encoding cuticle Col. Both
      Col possess the structural properties found in the type of Col that form the
      cuticle, such as short Gly-Xaa-Yaa interruptions and Cys clusters at conserved
      sites. On the basis of identical patterns of conserved cysteines, col-36 and col
      40 belong to the col-6 cuticle Col family. Semi-quantitative analysis using
      reverse transcription-PCR demonstrates that the col-36 transcript is present in
      L1 larvae and at the L1-L2 and L2d-dauer molts. The col-40 transcript is present
      in L1 larvae and at the L2d-dauer molt. Different members of the col-6 family are
      structurally related, but have different developmental expression patterns.

PMID- 8299961
TI  - A telomere-like satellite (GGGTCAT)n comprises 4% of genomic DNA of Drosophila
      hydei and is located mainly in centromeric heterochromatin of all large
      acrocentric autosomes.
AB  - We describe the isolation and analysis of a G+C-rich telomere-like (GGGTCAT)n
      satellite of Drosophila hydei. GGGTCAT-specific clones were obtained by a
      combination of restriction enzyme digestion and fractionation of D. hydei DNA by
      pulsed-field gel electrophoresis (PFGE). High-molecular-weight DNA (> 50 kb) was
      recovered from gels, sheared by sonication and cloned into the pBS plasmid
      vector. The results of PFGE analysis, quantitative dot blot measurements and
      fluorescence in situ hybridization (FISH) on metaphase chromosomes show that the
      tandemly arranged GGGTCAT sequences comprise 4% of genomic DNA and are organized
      as megabase-sized clusters in the pericentric region of all large acrocentric
      autosomes. A telomere-related function is rather unlikely, because the
      chromosomal ends of D. hydei seem to be free of GGGTCAT repeats and several other
      species of Drosophila do not contain any cross-hybridizing sequences at all.

PMID- 8299962
TI  - Isolation of the poly(ADP-ribose) polymerase-encoding cDNA from Xenopus laevis:
      phylogenetic conservation of the functional domains.
AB  - The complete nucleotide (nt) sequence of the Xenopus laevis poly(ADP-ribose)
      polymerase (PARP)-encoding cDNA was determined. The putative X. laevis PARP
      protein consists of 1008 amino acids (aa) with a molecular weight of 113 kDa. X.
      laevis PARP shares 74, 83, 73, 78 and 42% aa sequence homology with the human,
      bovine, mouse, chicken and Drosophila melanogaster PARPs, respectively.
      Comparison of the PARP aa sequences among these species showed conservation of
      two zinc-finger motifs in the DNA-binding domain, and an NAD-binding motif and a
      Rossmann fold in the catalytic domain. The first Leu of the putative leucine
      zipper of D. melanogaster PARP is substituted to Lys in X. laevis PARP. All the
      Glu residues in the leucine zipper are conserved in these six species.

PMID- 8299963
TI  - Conservation of the amino acid sequence of SV2, a transmembrane transporter in
      synaptic vesicles and endocrine cells.
AB  - SV2 is a secretory vesicle-specific protein produced by all neurons and by
      endocrine cells. The deduced amino acid (aa) sequence of this protein indicates
      that it is a transmembrane transporter [Bajjalieh et al., Science 257 (1992) 1271
      1273; Feany et al., Cell 70 (1992) 861-867; Gingrich et al., FEBS Lett. 312
      (1992) 115-122]. To determine the regions of the protein that are the most highly
      conserved throughout evolution, and might therefore be essential for the function
      of SV2, we isolated a cDNA clone encoding SV2 from the elasmobranch fish,
      Discopyge ommata, and compared the deduced aa sequence to two isoforms from rat,
      SV2A and SV2B [Bajjalieh et al., Proc. Natl. Acad. Sci. USA 90 (1993) 2150-2154].
      The comparison indicates that although the N-terminal cytoplasmic domain of SV2
      is the most divergent region, it contains a highly conserved sequence that is
      predicted to be the epitope for a monoclonal antibody that crossreacts with all
      species and two isoforms of SV2 [Buckley and Kelly, J. Cell Biol. 100 (1985) 1284
      1294; Bajjalieh et al., Proc. Natl. Acad. Sci. USA 90 (1993) 2150-2154]. The
      remainder of the protein is highly conserved: 62% of the aa in SV2 from D. ommata
      are identical to the rat SV2A sequence, and 12% are conservative substitutions.
      The high degree of conservation of this protein throughout evolution and across
      species indicates that it mediates a critical function of synaptic vesicles.

PMID- 8299964
TI  - Cloning and characterization of a cDNA encoding chicken liver alpha-N
      acetylgalactosaminidase.
AB  - Chicken liver alpha-N-acetylgalactosaminidase (alpha AGA) specifically removes
      terminally alpha-linked alpha-N-acetylgalactosamine from oligosaccharide chains
      on the surface of group A erythrocytes. Here, we report the molecular cloning of
      a alpha AGA cDNA by both library screening and PCR amplification. The clone
      contains a 1.2-kb 3'-untranslated region and 1.2-kb coding region which encodes a
      45-kDa protein. The protein was produced in bacteria and in rabbit reticulocyte
      lysate, and is specifically recognized on Western blot by an antibody raised
      against the purified chicken liver enzyme. Enzymatic activity was detected when
      alpha AGA was produced in Saccharomyces cerevisiae. The deduced amino acid
      sequence shows 80% homology with human alpha AGA and about 60% homology with
      alpha-galactosidases from a number of sources, indicating that these two families
      of exoglycosidases are evolutionarily related.

PMID- 8299965
TI  - Transcriptional regulation of the gene encoding apolipoprotein AI in chicken LMH
      cells.
AB  - Previous studies indicated that the differential expression of the chicken gene
      (ApoAI) encoding apolipoprotein AI (ApoAI) in the QMLA-29 and LMH cell lines may
      be the result of altered cis-elements and/or trans-acting factors. To examine the
      cis-elements, LMH DNA was used as a template and the 5'-upstream region of ApoAI
      was PCR amplified. The nucleotide sequence of the LMH ApoAI upstream region was
      identical to that obtained from young chicken liver DNA. Band shift analyses of
      the -87 to +90 bp upstream DNA of ApoAI showed differences in the shifting
      patterns when nuclear proteins from LMH and liver cells were used. Southwestern
      blots with the same DNA fragment and nuclear proteins from liver and LMH also
      showed differences. There was one common band of approx. 65 kDa. In addition, LMH
      had a trans-acting factor of approx. 26 kDa, while liver had an approx. 46-kDa
      protein. These data suggest that LMH has a different trans-acting factor which
      may downregulate ApoAI expression.

PMID- 8299966
TI  - Genomic structure of rat liver aryl sulfotransferase IV-encoding gene.
AB  - This report contains the first description of the genomic structure for a
      sulfotransferase (ST). The gene (ASTIV) encodes rat hepatic aryl ST IV, also
      known as tyrosine-ester ST (EC 2.8.2.9). A phage genomic clone containing 70% of
      the 3' AST gene coding sequence was isolated after screening a rat genomic
      library with an ASTIV cDNA. The remaining 5' sequence was determined from a PCR
      product obtained from rat genomic DNA and ASTIV cDNA-specific primers. ASTIV
      spans 3.5 kb and contains eight exons and seven introns. The fourth intron of
      this gene contains sequences homologous to rodent B1 repetitive elements and an
      Alu repeat found in rat. An alignment of the primary structures of ten different
      ST revealed several conserved regions, as well as a putative binding site for the
      cofactor for enzymatic sulfation reactions, 3'-phosphoadenosine-5'
      phosphosulfate.

PMID- 8299967
TI  - Sequence analysis and functional studies of interleukin-3 receptor alpha subunit
      encoding cDNAs amplified from KG-1 leukemic cells and normal human marrow.
AB  - Two partial cDNAs encoding the human interleukin-3 receptor alpha subunit (IL-3R
      alpha) were cloned from KG-1 leukemic cells using the polymerase chain reaction.
      Sequence analysis of these cDNAs predicted two single-amino-acid (aa) changes as
      compared with the published TF-1 leukemic cell IL-3R alpha sequence [Kitamura et
      al., Cell 66 (1991) 1165-1174]. These changes were confirmed by sequence analysis
      of a second set of independently derived cDNAs. Identical aa changes were found
      in the IL-3R alpha encoded by cDNAs cloned from normal CD34+ human marrow cells.
      Ligation of the partial cDNAs derived from KG-1 cells resulted in a full-length
      functional IL-3R alpha cDNA clone. Deletion of the extracellular 'LSXWS'
      consensus sequence resulted in complete loss of detectable [125I]IL-3 binding
      when this mutant receptor was co-expressed in COS-7 cells with the beta subunit
      of the IL-3 receptor.

PMID- 8299968
TI  - Cloning, sequencing and phylogenetic analysis of a human 5-hydroxytryptamine 1D
      receptor pseudogene.
AB  - A third member of the human 5HT1D gene family has been identified using a
      combination of homology cloning and DNA sequence analysis. This human gene is
      most related to the 5HT1D alpha subtype (77% shared identity) and is a
      pseudogene, based on the lack of an open reading frame (ORF) caused by multiple
      in-frame stop codons and nucleotide (nt) deletions relative to the functional
      5HT1D alpha gene (encoding the 5-hydroxytryptamine 1D alpha receptor). The 5HT1D
      pseudogene also contained an insertion that shares 87% identity to the Alu
      consensus sequence. Phylogenetic analysis of the three human genes in this family
      reveals that although the two functional genes, 5HT1D alpha and 5HT1D beta, are
      detected in all mammalian species examined, the 5HT1D pseudogene is only detected
      in a subset of primates (catarrhines) that evolved approximately 35-45 million
      years (Myr) ago. Alternatively, based on the 23% divergence between the
      functional 5HT1D alpha gene and the 5HT1D pseudogene, we estimate that these two
      genes began to diverge approximately 50 Myr ago.

PMID- 8299969
TI  - Purification and characterisation of the restriction endonuclease ItaI from
      Ilyobacter tartaricus recognizing 5'-GC decreases NGC-3'.
AB  - ItaI, an isoschizomer of the subclass IIW [Kessler and Manta, Gene 92 (1990) 1
      248] restriction endonuclease (ENase), Fnu4HI [Leung et al., Nucleic Acids Res. 6
      (1979) 17-25], has been isolated from Ilyobacter tartaricus. The ENase has the
      five-base palindromic recognition sequence, 5'GC decreases NGC-3'. It cleaves
      behind the second nucleotide and produces a one-nt 5' overhang.

PMID- 8299970
TI  - The alkane-inducible Candida maltosa ALI1 gene product is an NADH:ubiquinone
      oxidoreductase subunit homologue.
AB  - The ALI1 gene product in Candida maltosa was previously shown to be essential for
      n-alkane assimilation, possibly as a transcription factor [Hwang et al., Gene 106
      (1991) 61-69]. We show that the predicted sequence is highly homologous to a
      subunit of respiratory complex I from another fungus, Neurospora crassa, and from
      Bos taurus. The predicted protein contains a motif conserved in this subunit from
      mitochondria, chloroplasts and bacteria. It also contains an N-terminal sequence
      that suggests a mitochondrial (mt) localization and a role for mt respiration in
      n-alkane assimilation.

PMID- 8299971
TI  - Identification of alternate 5' untranslated regions in the gene encoding
      Ca2+/calmodulin-dependent kinase-G1.
AB  - Alternate 5' untranslated regions (UTR) of the Ca2+/calmodulin-dependent kinase
      Gr cDNA were identified by sequencing of anchored reverse transcription
      polymerase chain reaction (RT-PCR) products. Three alternate 5' ends of the mRNA
      were spliced at the same point to a common 5' UTR. A 3-kb EcoRI-BamHI genomic DNA
      restriction fragment containing the alternate UTR and 5' flanking sequence was
      characterized by sequence analysis and identification of several potential
      transcriptional control elements.

PMID- 8299972
TI  - Sequence of the mouse fibronectin-encoding gene promoter region.
AB  - The polymerase chain reaction (PCR) procedure has been utilised to clone, from
      mouse genomic DNA, a region of the fibronectin (FN)-encoding gene (FN) which
      includes the 5' flanking nucleotide (nt) sequences. The mouse promoter nt
      sequence shows high homology to the rat and human FN promoters, including
      consensus nt sequences for several DNA-binding transcription factors.

PMID- 8299973
TI  - Systemic blood pressure in glaucoma patients.
AB  - Blood pressure was monitored for 24 h in 32 control patients, 38 open-angle
      glaucoma patients referred because of decompensated IOP despite maximum
      treatment, 40 patients with open-angle glaucoma referred because of progressive
      damage despite controlled IOP, and 39 normal-tension glaucoma patients. In the
      control group a physiological drop in blood pressure during the night was
      observed. The patients referred with uncontrolled IOP had blood pressure very
      similar to that of the control group during both day and night. However, the open
      angle glaucoma patients with progression despite well-controlled IOP and also the
      patients with normal-tension glaucoma had markedly, and statistically
      significantly, lower systolic blood pressure during both day and night. The
      difference in diastolic blood pressure was smaller. Thus, blood pressure should
      be considered in diagnosis.

PMID- 8299974
TI  - Characterisation of the neovascularisation process in diabetic retinopathy by
      means of fractal geometry: diagnostic implications.
AB  - The neovascularisation formation and regression process of the peripheral retina
      in diabetic retinopathy was studied by means of fractal analysis. The fractal
      dimension of the local retinal vessel pattern was calculated to be significantly
      lower before formation of relevant neovascularisations than 2.5 years later,
      after formation of strong preretinal neovascularisations. Another year later the
      new vessels had regressed partially and the fractal dimension was again
      significantly reduced. This behaviour is almost independent of the representation
      of the vessel thickness during calculation. Since the retinal vasculature is a
      fractal, the fractal dimension appears as the "natural" measure of proliferative
      retinal vessel changes. It is demonstrated that the fractal dimension can be
      applied to characterise proliferative diabetic retinopathy. These features offer
      the possibility for computer-driven ("automated") quantitative characterisation
      of the treatment effect in proliferative diabetic retinopathy and possibly
      automated detection of proliferative diabetic retinopathy in the future. The
      limitations of the method are discussed.

PMID- 8299975
TI  - Minimum views required to characterize cataracts when using the Scheimpflug
      camera.
AB  - We performed Scheimpflug slit lamp photography and computerized image analysis on
      20 normal and 25 cataractous lenses using 18 slit images for each lens taken 10
      degrees apart. The data gathered from the normals served as the reference to
      estimate the accuracy of representation of the cataracts by the least number of
      views (18 and less) using a Fourier interpolative algorithm. Using the error
      obtained with one view for the normals, our study suggests that the minimum
      number of views necessary for adequate characterization is two for cortical
      cataracts, two for nuclear cataracts, and six for posterior subcapsular
      cataracts. This information will be useful in longitudinal studies of cataracts,
      since most researchers presently use only one view, which may be adequate for
      normals but not for cataractous lenses. We found the Fourier interpolative
      algorithm useful in estimating the minimum views required for the current method
      of analyzing Scheimpflug images, and it can be easily applied to other similar
      images.

PMID- 8299976
TI  - Comparison between the flicker test procedures of Aulhorn and of Dolle in the
      diagnosis of optic neuritis.
AB  - The use of the flicker test for diagnostic purposes is based on the absence of
      Brucke's effect during acute inflammation of the optic nerve. The test device of
      Aulhorn was compared with another, less expensive flicker test device, that of
      Dolle. The flicker test device of Aulhorn uses a mechanical projection system. In
      the device of Dolle, the flicker field is formed by electronically controlled
      groups of light-emitting diodes. In an initial examination, the reliability of
      Aulhorn's test was slightly higher than of Dolle's procedure. The normal ranges
      in 45 healthy subjects differed markedly between the two methods. One hundred and
      fifteen eyes of patients with established or suspected optic neuritis were also
      examined. Although there were differences in some conditions (e.g. shape and
      homogeneity of flicker field) due to the techniques, the specificity and
      sensitivity of the two methods were similar concerning the diagnosis of acute
      optic neuritis.

PMID- 8299977
TI  - A cluster and scotoma analysis based on empiric criteria.
AB  - From a collection of 288 visual fields of glaucomatous or glaucoma suspects, 30
      were selected at random and were analyzed by one expert interpreter. Visual field
      damage varied from nonexistent to severe. The interpreter defined clusters or
      scotomas subjectively according to adjacency criteria: adjacent test locations
      which exceeded a critical loss value were grouped as clusters or scotomas. A
      computer algorithm has been devised which simulates such evaluation methods. In
      general, a standard setting of several parameters produced a cluster display
      containing the same number of clusters as determined by the expert interpreter.
      Another display mode grouped clusters according to polygonal areas of a
      predetermined size (Voronoi diagram). Due to the broad selection of visual field
      defects, the specificity of the program with regard to various field decay
      patterns was small and it should thus be applicable to a broad spectrum of
      glaucomatous field damage.

PMID- 8299978
TI  - Quantification of congruence between the right and left visual fields.
AB  - In the past, congruence between the right and left visual fields could only be
      evaluated subjectively. This study presents a congruence index to assess the
      similarity of the two visual fields objectively and quantitatively based on
      probability calculations. In 18 patients with suprachiasmal lesions of the visual
      pathways (cerebrovascular accident or tumor), the index found a homonymous
      congruence in all cases (100%). Of 26 persons with pituitary adenoma, in 22 cases
      (85%) the index found heteronymous congruence. The validity of the method may be
      even higher, because all cases with atypical indices also had atypical congruence
      by subjective evaluation. Using this new method in 41 patients with primary open
      angle glaucoma, heteronymous congruence was detected in 73% and homonymous
      congruence was found in 17%. This new index may be useful for the development of
      computerized parametric methods of differential diagnosis.

PMID- 8299979
TI  - Optic nerve compression by carotid arteries in low-tension glaucoma.
AB  - Low-tension glaucoma (LTG) is manifested by glaucomatous optic nerve damage and
      visual field loss despite normal intraocular pressure (IOP). We describe 62
      patients with classical signs of LTG. Computed tomography (CT) was performed in
      all patients. In 56 of the patients (90.3%), pathology of the intracavernous
      carotid arteries adjacent to the intracranial opening of the optic canal could be
      demonstrated. In 28 patients (45.2%) a clear asymmetry of the optic nerve cupping
      was found and could be correlated with the severity of the carotid artery
      pathology. A control group of 24 age-matched patients included five (20.8%) with
      intracavernous carotid artery calcification and only one (4.2%) with
      intracavernous ectasia. We suggest that calcification, dilatation and ectasia of
      the carotid artery into the optic canal may play an important role in the
      pathogenesis of many cases of LTG. The close proximity of the carotid artery to
      the optic nerve at this location may result in compressive neuropathy with
      subsequent glaucomatous damage of the optic nerve head.

PMID- 8299980
TI  - Cellular fibronectin on intraocular lenses explanted from patients.
AB  - We investigated the origin of fibronectin (FN) on five posterior and four
      anterior chamber explanted intraocular lenses (IOLs) using immunohistochemical
      methods. Cellular deposits (assumed to be macrophages) and fibrous or membrane
      like proteinaceous deposits on the IOLs showed immunoreactivity to an antibody
      against cellular FN. These proteinaceous deposits were believed to be products of
      the cells that adhered to the IOLs.

PMID- 8299981
TI  - Morphological study of the cataractous lens of the senescence accelerated mouse.
AB  - A murine model of accelerated aging, the senescence accelerated mouse (SAM), has
      been developed. There are three accelerated senescence-resistant (SAM-R) strains
      and eight senescence-prone (SAM-P) strains. The SAM-P strains have an earlier
      onset and more rapid advancement of senescence resulting from a significantly
      shorter lifespan compared with the SAM-R strains. Spontaneous cataracts have been
      found in some individuals of the SAM-P/9 strain. The SAM-P/1 strain, which was
      used in the present study, has such systemic senescent characteristics as senile
      amyloidosis and alopecia, but it was previously thought that cataract does not
      occur in this strain. However, we found cataractous changes in the lens of these
      animals at early stages of their life. The earliest change was the appearance of
      a ripple-mark body at about 3 months of age. The number of rippled rings
      increased with age. These changes later induced refractive distortion of retinal
      vessels. Whole-mount flat preparations of the epithelium showed that the number
      of cells was markedly decreased at the advanced stages of cataract. At the late
      stages of life the lens cortex became liquefied and developed into a mature
      cataract. Cataract formation in this strain may be related to reduced viability
      of the lens epithelium.

PMID- 8299983
TI  - Transplantation of cultured human retinal pigment epithelium into rabbit
      subretina.
AB  - Transplantation of normal retinal pigment epithelium (RPE) into a diseased eye
      holds promise for treatment of several blinding disorders. Previous studies have
      involved immunosuppression and implantation of freshly isolated cells. We report
      here the successful transplantation of cultured human RPE cells into rabbits that
      were not immunosuppressed. A modified pars plana transvitreal technique was used
      for RPE transplantation. The cultured RPE cells, loaded with carbon as a marker,
      were transplanted into the denuded Bruch's membrane of albino rabbits. The
      animals were followed for from 1 week to 3 months. On histologic examination at 2
      months, no infiltrating lymphocytes were found in the vitreous cavity or choroid,
      even though Bruch's membrane was damaged. At about 3 months there were some
      macrophages in the subretina of transplanted eyes, indicating that an
      immunoreaction does occur eventually. Electron microscopy of the transplanted RPE
      showed apical-basal polarity and gap junctions. Restored function was attested to
      by the presence of phagosomes and phagocytosed outer segments in the transplanted
      cells. Our findings suggest that there is a weak, delayed immunoreaction to human
      RPE cells transplanted beneath the retina of the rabbit; however, functional
      recovery of the transplanted cells occurs before this immune response develops.

PMID- 8299982
TI  - Methylprednisolone therapy in laser injury of the retina.
AB  - The efficacy of methylprednisolone in argon-laser-induced retinal injury in
      primates was evaluated by clinical, histopathologic, and morphometric criteria.
      Methylprednisolone was given with a loading dose of 30 mg/kg followed by 5.4
      mg/kg per hour in three different regimens: (1) starting 24 h before laser and
      continuing for 4 days; (2) starting immediately after laser and continuing for 4
      days; and (3) starting immediately after laser and continuing for 8 h. Fundus
      photography, fluorescein angiography, and histologic examination showed
      significant beneficial effects of all three treatments compared to controls.
      Morphometrically, at the center of the lesion, the width of disrupted outer
      nuclear layer, the width of the affected RPE, and the percentage of residual
      photoreceptor nuclei confirmed the efficacies of treatment regimens 1 and 2, but
      not treatment regimen 3.

PMID- 8299984
TI  - Optimal test parameters for computerized quantitative layer-by-layer perimetry.
AB  - Quantitative layer-by-layer perimetry is a psychophysical technique believed to
      assess the functional characteristics of individual retinal layers. In the
      initial design of the technique, the test procedure was too time consuming for
      the testing of large field point patterns, and statistical treatment of the
      measured threshold values was difficult. Therefore, to minimize these
      limitations, a new design of quantitative layer-by-layer perimetry was developed
      by incorporating the technique into the existing hardware environment of the
      computerized perimeter Humphrey Field Analyzer. The present paper describes the
      theoretical considerations and experimental findings underlying a selection of
      optimal stimulus parameters to provide a basis for statistical treatment of
      measured threshold values, and to minimize test duration, while obtaining an
      acceptable estimate of the threshold level with minimum variance.

PMID- 8299985
TI  - Cellular sensitivity in allergic blepharoconjunctivitis due to phenylephrine eye
      drops.

PMID- 8299986
TI  - Antioxidant status and dietary lipid unsaturation modulate oxidative DNA damage.
AB  - High performance liquid chromatography with electrochemical detection (HPLC-EC)
      was used to measure 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker for oxidative
      DNA damage, in mammary gland isolated from tumor-bearing and tumor-free rats fed
      diets of varied fatty acid composition and vitamin E and selenium content. A
      method for tissue preparation and analysis is reported and a significant positive
      correlation shown between degree of unsaturation of dietary fatty acids and 8
      OHdG concentration, regardless of antioxidant status. The increase in 8-OHdG
      concentration with greater fatty acid unsaturation was more pronounced in the
      absence of adequate dietary vitamin E and selenium. The implications of these
      data for defining the role of dietary lipid in the process of mammary
      carcinogenesis are discussed.

PMID- 8299987
TI  - Reoxygenation-induced cell damage of isolated neonatal rat ventricular myocytes
      can be reduced by chain-breaking antioxidants.
AB  - To study the role of chain-breaking antioxidants on reperfusion injury in the
      ischemic heart, cultured ventricular heart cells (myocytes) were subjected to
      hypoxia and reoxygenation. The myocytes were prepared from neonatal rats and
      cultured in F10 medium that was supplemented with serum. As a marker for cell
      damage, lactate dehydrogenase was analyzed in the medium. Cells subjected to
      hypoxia for 5 h showed a 1.9 fold increase in lactate dehydrogenase (LD) leakage,
      while cells subjected to 1 h hypoxia followed by 4 h reoxygenation showed a 5
      fold increase in LD intake. Alpha-tocopherol, beta-carotene, nordihydroguairetic
      acid (NDGA), butylated hydroxyltoluene (BHT), and ICI211965 were added to the
      cell medium every 24 h for 6 d prior to reoxygenation. All compounds protected
      against reoxygenation-induced cell damage. In the presence of the 5-lipoxygenase
      inhibitor ICI211965, protection against LD leakage was found only at high
      concentrations, which corresponded to the antioxidative effect of ICI211965, and
      not to inhibition of 5-lipoxygenase. We conclude that cultured ventricular
      myocytes can be used to evaluate the protective effect of antioxidants on
      reoxygenation-induced cell damage, and that chain-breaking antioxidants protected
      well against reoxygenation-induced cell damage.

PMID- 8299988
TI  - Hydrogen peroxide production by red blood cells.
AB  - Red blood cells are frequently employed in studies of oxidative stress. Technical
      difficulties have previously prevented the measurement of H2O2 production by red
      blood cells, except during exposure to certain drugs or toxicants. We now show
      that a combination of glutathione depletion and 3-amino-1,2,4-triazole
      (aminotriazole) treatment can be used to measure the endogenous generation of
      H2O2 by red blood cells. In our studies, aminotriazole was used as an H2O2
      dependent (irreversible) catalase inhibitor, and catalase inhibition was used as
      an indirect measure of H2O2 production. Our results indicate that H2O2 is
      generated at a rate of 1.36 +/- 0.2 microM/h (3.9 +/- 0.6 nmol.h-1.g Hb-1), and
      that the steady-state red blood cell concentration of H2O2 is approximately 2 x
      10(-10) M. Kinetic comparisons of H2O2 production and oxyhemoglobin autooxidation
      (which generates O2.- that dismutases to H2O2) indicate that the latter is
      probably the main source of H2O2 in red blood cells.

PMID- 8299989
TI  - New approaches for measuring plasma or serum antioxidant capacity: a
      methodological note.

PMID- 8299990
TI  - Hemoglobin-based blood substitutes: potential free radical toxicity.

PMID- 8299991
TI  - Antioxidant activity of some diarylselenides in biological systems.
AB  - The selenoorganic compounds di(4-aminophenyl)selenide (10) and 4-nitro-4'-amino
      diphenylselenide (36) were shown to inhibit lipid peroxidation in
      ADP/Fe2+/ascorbate-treated microsomes and tert-butylhydroperoxide-treated
      hepatocytes with IC50s of 3 and 10 microM, and 14 and 10 microM, respectively. In
      the former system, these inhibition constants compare favourably with those of
      Ebselen and classical antioxidants such as butylated hydroxytoluene (BHT) and
      butylated hydroxyanisole (BHA). In the cell system, these selenium compounds were
      equipotent with BHA but more potent than Ebselen and its analogues. The diamino
      compound (10) was also an effective inhibitor of lipid peroxidation initiated by
      diquat redox cycling in hepatocytes, again being equipotent with BHA but more
      potent than Ebselen and its analogues, which actually stimulated lipid
      peroxidation in this test system. Manipulation of the amino functions of (10) and
      (36) by alkylation or acylation altered the antioxidant capacity. Optimal
      activity in this series was achieved by N-ethylation or N-isobutylation of (10).
      This produced antioxidants having IC50s below 1 microM in the microsome system, 3
      13 microM in the tert-butylhydroperoxide system, and being 100% effective in the
      diquat model at 50 microM. On the other hand, acylation or alkylation of the
      amino groups with long chain acyl or alkyl groups reduced the efficacy of the
      structures below that of the parent diamine. As with other antioxidant compounds,
      several of the chalcogenides were relatively selective inhibitors of monocyte 5'
      lipoxygenase-dependent secretion of LTB4 as compared to their effect on
      cyclooxygenase-dependent secretion of PGE2 (for example compound 42 had IC50s of
      0.6 microM and 10 microM, respectively). No correlation was observed between the
      redox-properties of the chalcogenides and their respective abilities to inhibit
      these enzymes.

PMID- 8299992
TI  - The role of O2.- in the production of HO.: in vitro and in vivo.
AB  - In vitro O2.- reduces Fe(III) to Fe(II), which, in turn, reduces the H2O2,
      yielding Fe(II)O or HO.. In vivo O2.- increases the supply of free iron by
      oxidatively attacking the [4Fe-4S] clusters of dehydratases such that they
      release Fe(II), which can then reduce H2O2. In vivo, O2.- also increases the
      production of H2O2 by acting as an oxidant toward the dehydratases and toward
      other cellular reductants.

PMID- 8299993
TI  - Update on free radical biology and medicine in countries of the former Soviet
      Union.

PMID- 8299994
TI  - Relative time-profiles for free radical trapping, coronary flow, enzyme leakage,
      arrhythmias, and function during myocardial reperfusion.
AB  - A new finding is the discrimination between vascular radical concentration and
      rate of myocardial radical formation to investigate the pathogenic role of free
      radicals for the heart. For that purpose, the perfusate radical concentration
      (U/ml) and the rate of myocardial radical formation (U/min) were determined
      (using the ESR spin trap technique), and were compared to functional recovery,
      cellular damage, and rhythm disturbances of the reperfusion-injured hearts. The
      vascular radical concentration (during the first 5 min of reflow) significantly
      correlated to coronary flow reduction (in the same period) and contractile
      failure (recovery after 30 min of reperfusion). A significant correlation was
      found between the time-courses of radical concentration and the incidence of
      arrhythmias. The myocardial formation rate of free radicals (during the first
      minutes of reperfusion) showed a significant correlation to the following total
      myocardial release of creatine kinase. The results support the hypothesis that
      free radicals in the vascular system of the heart may contribute to the
      functional deterioration of the post ischemic heart. Moreover, this study
      provides evidence that total radical formation in the heart muscle during the
      first minutes of reflow is involved in the induction of tissue injury during
      reperfusion that may lead to the subsequent loss of intracellular enzymes.

PMID- 8299995
TI  - Effects of gamma-linolenic acid, flavonoids, and vitamins on cytotoxicity and
      lipid peroxidation.
AB  - Gamma linolenic acid (GLA), a polyunsaturated fatty acid, promoted lipid
      peroxidation in Raji lymphoma suspension cultures, in a dose (10 microM-100
      microM) and time-dependent (4 h-48 h) manner. The increase in lipid peroxidation
      could be correlated to an increase in cytotoxicity. The plant flavonoids
      (quercetin, luteolin, butein, rutin) and the fat-soluble components (retinol,
      retinoic acid, alpha-tocopherol) by themselves did not affect lipid peroxidation
      in Raji cells. Quercetin, luteolin, retinol, and alpha-tocopherol were able to
      inhibit cell proliferation significantly. Although GLA only decreased the
      cytotoxicity of retinol-treated cells, the latter compound was able to block the
      prooxidative action of GLA by scavenging the free radicals induced by it.
      Quercetin at 50 and 100 microM exerted equipotent superoxide anion scavenging
      effects, but at the higher concentration it had no effect on lipid peroxidation.
      Although the bioactive test compounds are well known natural antioxidants,
      interestingly, our data showed that their potent cytotoxic actions do not involve
      free radicals or lipid peroxidation reactions.

PMID- 8299996
TI  - LDL modification by activated polymorphonuclear leukocytes: a cellular model of
      mild oxidative stress.
AB  - The purpose of this study was to determine the most potent activator of the
      respiratory burst of polymorphonuclear leukocytes (PMN) with respect to the
      oxidative modification of low density lipoprotein (LDL). Phorbol-12-myristate-13
      acetate (PMA), n-formyl-methionyl-leucylphenylalanine (nFMLP), lipopolysaccharide
      (LPS), and opsonized zymosan (OZ) were tested. The generation of reactive oxygen
      species by PMN was assayed as superoxide anion production. Oxidative modification
      of LDL was monitored by thiobarbituric acid reactive substance (TBARS) activity,
      by conjugated dienes formation at 234nm and by electrophoretic mobility on
      agarose gel. PMA was the most potent activator of PMN, inducing a 6-fold increase
      in the superoxide anion production, followed by OZ (3-fold increase). PMA
      activation also induced the greatest modification of LDL by PMN: 700% increase of
      conjugated dienes formation, 222% increase of TBARS, and 70% increase in the
      electrophoretic mobility. The indices of oxidative modification significantly
      correlated with the superoxide anion generated by different activators. Also, LDL
      oxidation by PMN was inhibited by superoxide dismutase but not by catalase,
      methionine, or hydroxyl radical scavengers. Our data indicate that PMNs activated
      by PMA produce a mildly oxidized form of LDL by a mechanism that appears to
      involve the superoxide anion.

PMID- 8299997
TI  - Effects of mild zinc deficiency, plus or minus acute phase response, on CCl4
      hepatotoxicity.
AB  - Low zinc (Zn) intake could be expected to compromise resistance to oxidative
      stress, even when accompanied by a normally protective acute phase response
      pretreatment. Mildly Zn deficient rats showed very high degrees of CCl4-induced
      hepatic cell membrane injury as assessed by serum sorbitol dehydrogenase
      activities. Rats pair-fed adequate Zn also showed above normal degrees of injury,
      but much less than rats fed low Zn. An acute phase response, elicited by leg
      inflammation, strongly protected rats consuming adequate Zn, either ad libitum or
      pair-fed, against the CCl4-induced rise in sorbitol dehydrogenase. However, the
      effect was partially absent in rats fed low Zn. Zinc intake had no effect on CCl4
      produced microsomal injury, assessed by glucose-6-phosphatase activities. Rats
      fed low Zn showed normal hepatic levels of metallothionein, a Zn protein with
      proposed antioxidant functions, but did not show the rise in metallothionein
      levels normally associated with acute phase response. In summary, mild Zn
      deficiency caused poor resistance to CCl4-induced plasma membrane injury and
      partially negated acute phase response protective effects. Metallothionein was
      not involved in the former effect, but may have contributed to the latter.

PMID- 8299998
TI  - Mathematical model supporting the superoxide theory of oxygen toxicity.
AB  - The discovery of superoxide dismutase was followed by a proposal that superoxide
      anion radical (O2.-) is a major factor in oxygen toxicity. The knowledge of
      superoxide chemistry, however, led some chemists to conclude that since O2.- is
      not very reactive in aqueous solution, the more reactive hydroxyl radical (HO.)
      was most likely to be the major damage causing species. Some have defended the
      superoxide theory by emphasizing that nonindiscriminate and selective reactivity
      could provide more toxicity than would high, indiscriminate reactivity. In the
      present study, network thermodynamic simulation was used to create a situation in
      which O2.- would selectively react with a substrate in a hypothetical sequence of
      subreactions supporting biological processes. In this situation, when the
      simulation of the chemical reactions was carried out using reasonable parametric
      values found in the literature, the selective reaction of O2.- to one molecule in
      the sequence caused a 95% disruption of the observable process, whereas
      indiscriminately targeted HO. attack caused only 0 to 35% inhibition. The major
      cause of the weak effect of HO. was found, in this particular model, to be a lack
      of sufficient availability of HO. due to both its slow generation by the Fenton
      reaction and a large demand for reactions with inconsequential targets. This
      model supports the superoxide theory of oxygen toxicity by demonstrating that a
      simple set of circumstances can quantitatively lead to the proposed selective
      superoxide toxicity. The present study also advocates the use of novel network
      thermodynamic simulation techniques for solving problems concerning biological
      oxidants and antioxidants.

PMID- 8299999
TI  - The oxidative inactivation of cytochrome P450 in monooxygenase reactions.
AB  - Possible mechanisms of cytochrome P450 self-inactivation during catalytic
      turnover have been considered. Two ways of hemoprotein inactivation are so far
      known. The first, studied extensively by many authors, is the formation of active
      substrate intermediates, capable of modifying heme and apoenzyme. The second way,
      revealed quite recently and resulting from uncoupled cytochrome P450-catalyzed
      monooxygenase reactions, is yet to be clarified. Briefly, it involves formation
      of hydrogen peroxide in the hemoprotein active center, which interacts with the
      enzyme associated Fe2+, thereby generating hydroxyl radicals that bleach the heme
      and modify the apoenzyme. This mechanism operates with substrates and cytochrome
      P450 forms with partially coupled monooxygenase reactions, thus causing the
      formation of hydrogen peroxide as a byproduct.

PMID- 8300000
TI  - Reactive oxygen species, chromosome mutation, and cancer: possible role of
      clastogenic factors in carcinogenesis.
AB  - Superoxide radicals may induce genotoxic effects by indirect action mechanisms,
      implicating the formation of more long-lived, secondary clastogenic material
      called chromosome breakage factors or clastogenic factors (CF). CF are produced
      via the intermediacy of superoxide, and stimulate further superoxide production
      by competent cells. This results in a selfsustaining and longlasting process of
      clastogenesis, which may exceed the DNA repair system and ultimately lead to
      cancer. An increased cancer risk is indeed observed in conditions accompanied by
      CF formation. These include irradiated persons, asbestos workers, patients with
      chronic inflammatory diseases, HIV-infected persons, and the congenital breakage
      syndromes ataxia telangiectasia, Bloom's syndrome, and Fanconi's anemia. Because
      reactive oxygen species (ROS) are implicated in CF formation and CF action,
      antioxidants may be protective as anticlastogens and consequently as
      anticarcinogens. In persons at high risk because of their occupation, life style
      or place of residence, the presence of CF may represent an indication for
      chemoprevention of cancer by antioxidants. CF can be useful as biochemical
      markers and intermediate endpoints for the evaluation of promising drugs. They
      are therefore not only of interest as a mechanism by which ROS may exert
      genotoxic effects, but also have practical implications.

PMID- 8300001
TI  - Induction and measurement of antisperm antibody responses in vitro.
AB  - Using the Mishell and Dutton culture system an assay was developed for eliciting
      and quantifying sperm surface antigen (SSA)-specific immune responses in vitro.
      Peripheral blood mononuclear cells (PBMC) from sexually inexperienced and
      experienced women that were antisperm antibody (ASA) negative gave rise to a
      plaque-forming cell (PFC) response of similar magnitude (1,362 and 1,254
      PFC/culture, respectively). PBMC from women that were ASA positive had lower PFC
      responses if cervical mucous antibodies were detected along with circulating
      antibodies (876 PFC/culture) than if they were not detected (1,512 PFC/culture).
      Limit dilution analysis was used to demonstrate that the level of the anticipated
      antibody response is regulated by T helper cell activity. The results of this
      investigation suggest that the antibody response to SSA is governed at least in
      part by both the secretory immune system and circulating T helper cells.

PMID- 8300002
TI  - Congenital malformations after immunotherapy for habitual abortion: is there an
      increase?
AB  - The risk of congenital malformations as assessed in infants born to women who
      underwent immunotherapy for habitual abortion. One hundred and eighty women were
      immunized with paternal mononuclear cells and 85 were not. Of 135 pregnancies in
      immunized patients, 27 (20%) were miscarriages, and 4 of the remaining 108 had
      congenital malformations. Two (encephalocele and common AV canal) were diagnosed
      in the 20th and 21st week of gestation. A case of esophageal atresia and Fallot's
      tetralogy were diagnosed at birth. Of 65 pregnancies in the non-immunized group
      38 (58.5%) were miscarriages, and of the remaining 27, 1 case of Down's syndrome
      occurred. In a subgroup of 7 habitually aborting couples with parental balanced
      chromosomal anomalies, the balanced translocation was transferred to the infant
      in 1 case. No other congenital anomalies were found in either group.
      Consequently, these anomalies are probably not the result of abnormal pregnancies
      retained as a result of immunization.

PMID- 8300003
TI  - Differential suppression activity induced by paternal leukocyte immunization in
      habitual abortion.
AB  - In order to investigate the possible role of suppressor cells in paternal
      leukocyte immunization to prevent recurrent miscarriages, peripheral blood
      lymphocytes from habitually aborting women before and after immunization were
      assessed. Immunization-induced suppressor activity as shown by (1) rise in CD8
      positive cells and a decline in the CD4/CD8 ratio, (2) failure of cyclosporine A
      to inhibit the proliferation of phytohemagglutinin- and alloantigen-stimulated
      cells and (3) unresponsiveness to the immunizing spouses' antigen. These findings
      resembled those in normal pregnant women. Hence, paternal leukocyte immunization
      may induce specific and nonspecific T cell suppression which may induce the
      immune tolerance necessary to maintain pregnancy.

PMID- 8300004
TI  - Increased levels of plasma thrombomodulin in preeclampsia.
AB  - Plasma levels of thrombomodulin (TM), a glycoprotein found on the surface of the
      endothelial cells, are elevated in certain diseases that are characterized by
      damage to the vascular endothelium. Such damage is thought to be involved in
      preeclampsia. We therefore studied the plasma levels of this substance in 13
      preeclamptic women as compared with 14 normal pregnant and 16 nonpregnant women.
      We found that the plasma levels of TM were significantly elevated in preeclamptic
      women vs. controls. A significant positive correlation was observed between the
      plasma TM level and that of serum creatinine. It is thus suggested that elevated
      TM levels in preeclampsia may reflect a decrease in renal clearance rather than
      vascular endothelial damage.

PMID- 8300005
TI  - A new technique for improved diagnosis of local placental abnormalities: Fourier
      analysis of intraplacental waveforms.
AB  - A new method to diagnose localized placental lesions is introduced. The method
      involves Fourier analysis of intraplacental and umbilical Doppler velocity
      waveforms. It is shown, using a theoretical model based on an electrical
      transmission line approach, that intraplacental waveforms that are of higher
      pulsatilities than those in the umbilical artery indicate placental
      abnormalities. The method was applied in a series of cases with normal umbilical
      waveforms in which placental abnormalities were diagnosed. The method promises to
      be more sensitive and specific than analyzing umbilical waveforms alone as it
      does not depend on uncertain threshold values.

PMID- 8300006
TI  - Prevalence of anti-cardiolipin antibody in habitual aborters.
AB  - An enzyme-linked immunosorbent assay was developed for the detection of
      anticardiolipin antibody (ACA) in habitual aborters. Results above the 98th
      percentile of a distribution of 100 blood donors were considered to be positive.
      Specific binding index for ACA was higher in 20 patients with at least 3
      consecutive spontaneous abortions (group A) than in 20 women with at least one
      live birth without pregnancy wastage (group B). ACA was detected in 4 patients of
      group A and in none of the women of group B. Most of the pregnancy wastages
      occurred after the first trimester in ACA-positive patients and during the first
      trimester in ACA-negative patients.

PMID- 8300007
TI  - Pregnancy interruption by vaginal misoprostol.
AB  - A total of 132 pregnant women with average gestational age of 14.2 weeks (range
      11-22 weeks) undergoing legal abortion volunteered for a trial utilizing vaginal
      administration of misoprostol. In 106 women a dose of 800 micrograms was
      utilized, whilst in 26 women 1,200-1,600 micrograms were given. Nonsurgical
      expulsion of the fetus was successful in 117 cases (88.6%). Four cases had to be
      excluded for various social reasons. A total of 11 did not achieve fetal
      expulsion within 56 h after application of misoprostol. These cases (11/132;
      8.3%) were considered failures. Previous reports in the literature of toxicity
      trials on animals reporting no fetotoxic nor teratogenic effects of misoprostol
      at doses up to 10,000 micrograms/kg body weight seem to be of no validity in the
      human since we could demonstrate that almost 80% of pregnancies were interrupted
      at a dose of 10-15 micrograms/kg body weight. The conclusion is that vaginal
      administration of this prostaglandin analogue, not requiring cool temperature for
      storage, is remarkably effective in achieving safe interruption of pregnancy
      without any significant complications.

PMID- 8300008
TI  - Sub-50 oral contraceptives affect folate kinetics.
AB  - The effects of long-term use of oral contraceptives containing less than 50
      micrograms of estrogen (sub-50 OCs) on the kinetics of folic acid monoglutamate,
      vitamin B12 levels, and iron status have been studied in 29 OC users (Marvelon)
      and in 13 women without OC use serving as controls. At 210 min after oral folate
      loading the median serum folate concentration was significantly lower in OC users
      when compared to the control group. OC users showed significantly higher total
      iron binding capacity and significantly lower serum vitamin B12 concentrations.
      This data demonstrates that sub-50 OCs significantly affect folate kinetics and
      vitamin B12 levels. However, the folate and vitamin B12 status does not seem to
      be at risk.

PMID- 8300009
TI  - Progesterone reduces sympathetic tone without changing blood pressure or fluid
      balance in men.
AB  - There is scant information on the effects of progesterone on circulation. Changes
      in catecholamine levels, blood pressure and transcapillary fluid balance were
      measured in 12 men before and during administration of natural progesterone
      (Utrogestan). Before administration, systolic blood pressure was significantly
      correlated with venous adrenaline (r = 0.67, p = 0.01). There was a significant
      decrease (p = 0.004) in venous noradrenaline during progesterone administration,
      and systolic blood pressure was significantly correlated with the arteriovenous
      difference for noradrenaline (r = 0.66, p = 0.02). Serum progesterone, which
      attained levels similar to those found in women during the luteal phase, did not
      significantly alter blood pressure, body weight or intra- to extravascular fluid
      shift. It is concluded that progesterone may have a direct action by increasing
      the uptake of noradrenaline from the synaptic cleft or by decreasing the nerve
      firing rate. Interestingly, the pretreatment finding of a significant correlation
      between blood pressure and adrenaline was less evident during progesterone
      administration.

PMID- 8300010
TI  - Value of perinatal audit in obstetric care in the developing world: a ten-year
      experience of the Maputo model.
AB  - A decade of perinatal audit in the Maputo Central Hospital is reviewed with the
      objective of addressing the potential value of the audit process in monitoring
      the different constituents of morbidity and mortality in the perinatal period.
      The perinatal mortality showed a significant but transient change during the
      observation period 1982-1991, while intrapartum fetal mortality was significantly
      reduced from 10.9 to 3.9 per thousand (p < 0.0005). Staff members were sensitized
      towards immediate and long-term effects of implemented surveillance routines by
      regular feedback of perinatal data on visible wall charts and by weekly
      conferences. The advantages of a comprehensive audit approach in perinatal
      medicine comprising both maternal and fetal/infant aspect are underscored. An
      ethical commitment to nonconfidential straight-forwardness and open-mindedness in
      critical discussions regarding mismanagement is emphasized for a successful audit
      strategy.

PMID- 8300011
TI  - Asymptomatic paroxysmal atrial fibrillation during intravenous magnesium sulfate
      treatment in preeclampsia.
AB  - Magnesium sulfate is commonly used as the anticonvulsant drug of choice for
      preeclampsia and eclampsia. It is effective, nontoxic to both mother and fetus,
      and side effects are rare within the therapeutic range. This report describes
      paroxysmal atrial fibrillation occurring at low serum levels of the drug during
      the treatment of preeclampsia.

PMID- 8300012
TI  - Umbilical and arcuate uterine artery flow velocity measurements during acute
      hemodialysis.
AB  - Dialysis during pregnancy is a rare event associated with a poor outcome. The
      acute fluid volume shifts during hemodialysis are suspected to be one of the
      reasons for the high rate of complications during the procedure. This is the
      first report of uteroplacental and fetoplacental perfusion assessment during
      acute hemodialysis in pregnancy. The results of the Doppler measurements suggest
      that the maternal-fetal circulation can successfully tolerate acute volume shifts
      provoked by hemodialysis.

PMID- 8300013
TI  - Dying for art.

PMID- 8300014
TI  - The sublingua and tongue of Tupaia (Scandentia, Mammalia): a scanning electron
      microscope study.
AB  - The surface morphology of the tongue and the sublingua in Tupaia belangeri was
      examined both under the dissection microscope and with the scanning electron
      microscope. Shape and structural differentiation of the sublingua and the
      anterior ventral part of the tongue are described. Special types of papillae were
      found on the lingual segment of the keel, along the serrated edges of the
      sublingua, and at the apex linguae. The findings are discussed with respect to
      the special conformation of the oral cavity of Tupaia and in relation to the
      evolutionary and functional significance of the tongue and the sublingua in this
      species.

PMID- 8300015
TI  - On the occurrence of nocturnal and diurnal loud calls, differing in structure and
      duration, in red howlers (Alouatta seniculus) of French Guyana.
AB  - Structural patterns and 24-hour rhythms of the loud calls of Alouatta seniculus
      were studied in a wild population living in primary rain forest in French Guyana.
      These loud calls are low-pitched noisy hoarse sounds with an upper frequency
      limit around 3,000 Hz. Their spectral energy is concentrated in two clusters,
      each of which includes two dominant frequency bands. Loud calls comprise one or
      several vocal units with alternating crescendos and decrescendos. Five different
      types of units can be distinguished. Depending on their duration, loud calls can
      be roughly divided into two classes: long and short calls. Long calls (mean
      duration 3.28 min) include three phases. After the end of the calls, one or two
      blowing noises of weak amplitude may be heard. Short calls (mean duration 11 s)
      are frequently uttered in clusters of several calls given by the same troop at
      intervals of a few seconds to a few minutes. Observations carried out over the 24
      hour cycle show that the calling rate is higher at night, with a peak around dawn
      and that long calls are more frequent at night, while short calls are mainly
      heard during the day. Most long calls are emitted from the sleeping sites and
      carry great distances. They probably play a role in inter-troop communication.
      Despite their intensity, short calls are used for short-distance communication.
      The occurrence of two different loud calls in Guyanan howlers and the amount of
      night calling in these monkeys are discussed with reference to studies of other
      howler populations.

PMID- 8300016
TI  - Kinship and different dominance styles in groups of three species of the genus
      Macaca (M. arctoides, M. mulatta, M. fascicularis).
AB  - Single groups with small matrilines of 3 species of the genus Macaca (M.
      arctoides, M. mulatta, M. fascicularis) were investigated. The aim of the study
      was to find out how affiliative preferences towards close kin correlate with the
      distribution of aggression and support in agonistic encounters among individuals,
      and whether such tendencies differ between species with different dominance
      styles. It was found that aggression between kin was less frequent than between
      non-kin in all 3 groups. Kinship was not a decisive factor in the choice of
      partners for close spatial proximity in any of the 3 species. Animals preferred
      to groom relatives significantly more frequently only in the M. mulatta group. A
      kin effect was clearly expressed in the choice of objects of support in
      aggressive conflicts in M. mulatta and M. fascicularis, whereas in M. arctoides
      such an effect was absent. In the M. mulatta and M. arctoides groups, animals
      preferred to support victims, while in the M. fascicularis group aggressors were
      preferentially supported. Our data supported conclusions about differences in the
      number of social parameters in species with different dominance styles. In
      species with relaxed social hierarchies (M. arctoides), there is a strong
      tendency towards cohesive relations with all social categories, while in groups
      with rigid hierarchies (M. mulatta; M. fascicularis) cohesive tendencies are
      largely concentrated in the direction of related individuals.

PMID- 8300017
TI  - Sexual dimorphism of skull and dentition in Phayre's leaf monkey (Presbytis
      phayrei).

PMID- 8300018
TI  - Drug policy and the system of care and treatment in the Federal Republic of
      Germany.
AB  - In this article the absurdity of the prevailing drug policy in the Federal
      Republic of Germany is shown. The hithero existing system of care and treatment
      has been determined by the logic of criminalization; moreover, its range and
      effect was rather small. Instead of at least making corrections to this
      ineffective and inhuman system, German drug policy continues--despite some
      promising alternative approaches in some of the federal states--according to the
      slogan 'more of the same' and propagates the 'war on drugs'. The author, however,
      pleads for a 'change of paradigm' in drug policy, in which the idea of
      acceptance, decriminalization, pluralization of offers as well as communication
      orientated drug-prevention would play a prominent role.

PMID- 8300019
TI  - Neuropathologic analysis of postmortal brain samples of HIV-seropositive and 
      seronegative i.v. drug addicts.
AB  - Between 1987 and 1992 we performed forensic-pathologic and neuropathologic
      examinations on 70 cases of i.v. drug addicts who died of an overdose. In almost
      25% of the cases HIV-positivity was revealed by serological examinations. In all
      the cases, irrespective of the result of the serological examination, a diffuse,
      reactive astrocytosis was the most prominent histologic alteration, accompanied
      by more or less pronounced regressive changes of this cell type in the deep
      layers of the white matter. Furthermore, also in all the cases, a slight to
      moderate, reactive proliferation of microglia could be assessed. In a few cases
      of the HIV-seropositive group a lymphocytic meningitis, viz. meningoencephalitis
      was found; these changes may indicate an early invasion of the central nervous
      system (CNS) by the HIV. In spite of these inflammatory alterations, in the
      latter cases no HIV-specific antigens (p24 and gp41) could be demonstrated in the
      brain, most probably because of the small number of infectious particles. In
      order to reveal the earliest phase of invasion of the CNS by the HIV, we
      performed a search for HIV-specific nucleic acid sequences by the aid of the
      polymerase chain reaction (PCR) in 8 HIV-seronegative and 8 normal control cases.
      Although, most probably due to contamination, also the control cases exhibited
      some PCR-signals, these were more pronounced and appeared with more primer-pairs
      within the group of HIV-seronegative drug addicts. It is conceivable that HIV
      penetrates the CNS and is harboured in it in latent form shortly after the
      primary infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300020
TI  - Local measures for the reduction of drug emergency risks and drug mortality
      risks.
AB  - The alarming increase of drug mortality rates in Germany was followed by research
      projects to enlighten the causes of this increase. The results of the Bremen,
      Hamburg and Berlin studies 1991-92, led to the conclusion that specific risk
      constellations have to be considered in the process of improving the drug
      counselling and health care system in the community. Primary prevention measures
      in kindergartens and schools, special services for families with addiction
      problems, decriminisation of drug abuse, the strengthening and specialisation of
      the counselling system and health services and new intervention strategies
      including methadone substitution should be integrated into local drug plans.

PMID- 8300021
TI  - Drug emergencies in Bremen in 1991 and 1992.

PMID- 8300022
TI  - Drug emergency patients are a burden for the medical care system: inadequate care
      for drug emergency patients.
AB  - During the course of the Drug Emergency Study in Bremen it became obvious that
      there are many problems left unsolved related to the medical care of intoxicated
      heroine addicts. From January to June 1992 there were 1230 drug emergencies, 409
      hospital admissions and 644 emergency transportation. With or without antidote
      treatment, most patients leave the medical care system as soon as possible
      because of withdrawal symptoms. The physicians involved answered a short
      questionnaire about these problems: 80% of the physicians are dissatisfied with
      the present medical care situation for intoxicated drug addicts and feel that
      these patients are a burden for the hospitals (81%) and for themselves (73%); 93%
      of the physicians think that a central drug emergency unit, offering medical and
      psycho-social care would solve the present problems and would be a possibility
      for lowering drug emergencies and, as a further result, drug mortality.

PMID- 8300023
TI  - Drug-related death--an update.
AB  - Some epidemiological, morphological and toxicological aspects from a continuous
      prospective study of drug-related fatalities in Hamburg are described. The lethal
      risk for intravenous drug addicts (IVDA) has increased (1990: n = 136 drug
      related fatalities in Hamburg; 1991: n = 184). Infectious diseases are common.
      From the epidemiological point of view the HIV-1 prevalence is decreasing;
      hepatitis C turned out to be a serious medical problem for IVDA. The fatal course
      of the addiction is mostly caused by heroin overdosage (sometimes in combination
      with ethyl-alcohol, benzodiazepines and barbiturates); about 40% of the
      fatalities were alcoholized (20% with a blood alcohol concentration of more than
      1%).

PMID- 8300024
TI  - Etiology of accidental/unexpected overdose in drug-induced deaths.
AB  - The life-threatening risk for drug addicts is the accidental/unexpected overdose
      (in Germany mostly caused by opiates). The problem of drug addiction, which
      encompasses all aspects of the individual's life, is accompanied by the
      additional negative reinforcement of the permanent danger of a sudden fatal
      outcome. The causes for an accidental fatal intoxication originate from the
      different qualities of heroin, the reduced tolerance of the body and carelessness
      in consuming drugs. These determinants are influenced by several indirect
      phenomena, as for example psycho-social, therapeutic, legal and economic
      problems. Furthermore, we have often observed critical life events shortly before
      death and/or a latent inclination to suicide.

PMID- 8300025
TI  - Drug death autopsies at the Munich Institute of Forensic Medicine (1981-1992).
AB  - A total of 638 drug death autopsy cases in southern Bavaria from 1981 to 1992
      were analysed, including epidemiological and toxicological investigations. The
      rate of HIV infections decreased during the last few years. Cocaine does not
      (yet) play a major role. Suicide rates are high. Heroin intoxications are the
      most frequent cause of death, mostly in combination with other drugs and alcohol.
      In 1992 we observed a sharp increase of the number of deaths associated with
      dihydrocodeine abuse. This seems to be a local phenomenon and has to be explained
      by uncritical and uncontrolled prescription of large amounts of this opiate by
      individual physicians.

PMID- 8300026
TI  - A survey of drug deaths in western Austria.
AB  - We evaluated the drug deaths in western Austria during the period from 1981 to
      1991. The increase of fatal cases is partly due to a change in statistical
      methods and the definition of 'drug victims'. In this paper a survey is given
      concerning the drug deaths investigated forensically and toxicologically in our
      area of responsibility.

PMID- 8300027
TI  - Preliminary results of an interdisciplinary survey of drug victims.
AB  - In an interdisciplinary study, 53 cases of drug-related death were investigated.
      Forty per cent of these cases exhibited acute or chronic hepatitis; foreign body
      granulomas were detected in 30%. By CT-scan of the left lung, small abscesses and
      pneumonic focuses could be localized. The spectrum of bacterial strains isolated
      from lung tissue did not differ significantly from that of a control group.
      Severe alterations of the testes, i.e. reduction of spermatogenesis, was present
      in a considerable number of cases. The high rate of myocarditis diagnosed (18%)
      supports the idea that besides acute intoxication, drug-related death is due to
      multifactorial origin.

PMID- 8300028
TI  - Drugs and AIDS in Southeast-Asia.
AB  - Opium dependence was indigenous to countries in the Golden Triangle area in south
      east Asia (SA). Heroin epidemics developed in most SA countries in the 1960s and
      early 1970s and remained a significant problem particularly in Myanmar, Thailand
      and Malaysia until now. In contrast, the island countries in SA seemed quite free
      from opiate abuse. Intravenous injection (IV) of drugs appeared after the heroin
      epidemic and currently prevails in countries with a significant opiate abuse
      problem. IV of opium was particularly common in the highly urbanized cities in
      Vietnam. Most SA countries started HIV seroscreening in IV drug users (IVDU)
      around the middle of the 1980s. Rapid epidemic spread of HIV infection was
      observed in 1988-89 in Thailand and Myanmar. The Highest prevalence of more than
      80% was reported from a study of IVDUs in Yangon, Myanmar, followed by Thailand
      at about 40%. Although HIV infected IVDUs were identified at the same time in
      Malaysia and later in Singapore and the Philippines, there was no evidence of
      such a rapid and severe epidemic.

PMID- 8300029
TI  - Typology of drug abuse deaths in Hamburg.
AB  - Based on a multidisciplinary approach (social-scientific questionnaire and
      forensic-pathological investigations), a typology of the drug-related fatalities
      in Hamburg during the period from July 1991 to June 1992 was achieved. A
      distinction between 3 types of addicts is proposed. Each group represents a
      different consumption pattern: (1) the opioid type, (2) polyvalent-drug users,
      and (3) primary alcoholics. With respect to these 3 types of abuse, some medical
      (concentration of alcohol and opioids in the blood) and social-scientific data
      (age at the beginning of the drug career, consumption of different drugs,
      distribution of age and sex, the quality and frequency of contact to facilities
      of the drug aid in Hamburg) are discussed.

PMID- 8300030
TI  - Undetected drug addict fatalities.
AB  - A urine screening in fatalities with an unnatural or unknown cause of death (13
      40 years of age) was carried out to evaluate the proportion of undetected drug
      related cases. Ten out of 160 fatalities without a hint of drug consumption were
      classified as drug-related according to the definition of the Bundeskriminalamt;
      5 of them committed suicide. Moreover, we found a relevant amount of AIDS deaths
      from the risk group of intravenous drug addicts not registered as drug-related
      deaths.

PMID- 8300031
TI  - Comparison of drug abuse fatalities and emergencies.
AB  - During a 9-month period, drug abuse emergencies were investigated prospectively
      and compared with drug-related fatalities of the same period. The emergency
      patients were of younger age, the proportion of women and the prevalence of
      infections with HIV, HBV and HCV was higher than in drug-related deaths.
      Additional alcohol consumption was similar in both groups but more frequent in
      drug-addict emergencies where the patients were 20-30 years of age. It is
      suggested that the emergency patients might characterise a special risk group of
      drug addicts and might be a target for interventional help to prevent fatalities.

PMID- 8300032
TI  - Drug abuse emergencies in Hamburg 1990/91.
AB  - During a 30-month investigation of the prevalence and structure of drug
      emergencies in Hamburg, data from all ambulances were analysed. From January 1991
      to June 1992 there were 1565 drug-related emergency patients suffering a life
      threatening event in Hamburg (1097 male, 350 female, 118 without information
      concerning the sex) to whom medical care was given by an emergency team. The
      number of cases grew strongly from 538 in 1990 to 720 in 1991. The place where
      the patients were found was very often in the region around the main railway
      station and near to the Reeperbahn, but we could also observe a scene south of
      the river Elbe.

PMID- 8300033
TI  - Juvenile delinquency and drug dependence in Hungary.
AB  - It is regretable that the delinquency has increased in Hungary over the past 15
      years. This fact occurred because criminality increased to a greater extent than
      average, and this means a steady supply of adult criminals. According to the
      surveys of the forensic psychiatrical records carried out over the 4 years
      between 1987-1990 in archival material of our Department, the criminological
      factors which occurred most frequently in juvenile delinquency among the 14-18
      year-old age group are immature personality, endangered family background and
      inadequate school attendance. Thirty percent of criminal acts could be connected
      with alcoholism, 65% with theft, and 22% with aggressive delinquency. An
      important role in the increasing juvenile delinquency must be attributed to the
      crisis of the previous regime, including the faulty endeavours in child and youth
      protection and the inefficient school system. The decrease in living standards
      and the employment of women in work contributed to the loosening of family
      relations and the dereliction of children's education. The proportion of
      institutional young people among the perpetrators is high. Another factor with
      regard to the disadvantageous situation is the migration of young people to the
      towns from villages. Without the necessary conditions and with the poor company
      of friends, this presents an intensified criminological danger. Prevention is
      obviously of outstanding importance. The improvement of the economic situation,
      stability of families, substantial changes in school reform, the fight against
      alcoholism and the modern judicial regulation can be the means to achieve this
      goal.

PMID- 8300034
TI  - Basic concepts of treatment and rehabilitation of drug dependence and how they
      are counteracted by the legalizing debate.
AB  - Basic treatment of drug dependent patients begins with detoxification and
      diagnosis of drug related and drug induced diseases. The therapeutic approach has
      to be oriented on the career of drug addiction itself and constitutional
      psychopathology. Patients must undergo specialized care if the drug dependence is
      complicated by accompanying diseases. All patients experience a life without
      drugs on rehabilitation programs. Treatment is defined both by a highly
      structured milieu and by the intention of getting the patient acquainted to a
      self-determined life. Subsequently, a carefully designed follow-up program is
      needed. Present debates about legalization of drugs diminish the readiness of the
      youth to do without drugs.

PMID- 8300035
TI  - Advantages and disadvantages of the alternatives of private practice, public
      health office and clinic out-patient department as dispensaries for methadone
      substitution of drug users.
AB  - In Germany, methadone substitution will be expanded considerably. Pilot projects
      and single private practitioners collected first experiences. Other programmes
      and practitioners follow, since important obstacles have been removed. Instead of
      individual solutions for limited numbers, broader concepts must be developed.
      Private practice, public health office and clinic out-patient departments each
      offer advantages and disadvantages. In several surveyed cities, there are a
      variety of substitution facilities and no general solution. Local facilities have
      to be examined for their advantages and disadvantages and should be connected
      cooperatively--e.g. containing a central out-patient department and a number of
      private practitioners--to serve the needs of the patients and the efficacy of the
      system.

PMID- 8300036
TI  - Methadone-substitution and driving ability.
AB  - A general statement about the driving ability of HIV-positive as well as HIV
      negative addicts undergoing methadone-substitution treatment cannot be made with
      certainty. Even isolated observations are not significant; only an individually
      performed assessment, free of prejudice and conscientiously done is decisive. The
      formal assertion that addiction equals driving-inability, which is largely
      practised at present, is inadmissible and therefore harmful to the therapeutic
      efforts for rehabilitation.

PMID- 8300037
TI  - Correlation between disease and community: is drug addiction a problem of fringe
      groups?
AB  - Addiction, because of its associated psychological and physical diseases, is
      producing increasing expenses through social burden and influencing the
      epidemiological situation of the whole population via sexual or simple intimate
      social contacts. Outstanding infectious diseases with a high incidence in drug
      addicts are tuberculosis, hepatitis A, hepatitis B and the classical notifiable
      venereal diseases. Preventive measures are required, involving immunization and
      isolation. HIV infection is another increasing problem in drug addicts. The
      relatively long asymptomatic course in this population also raises the potential
      for the spread of AIDS to the general population. There is no ideal method for
      preventing this danger, but because the traditional abstinence paradigm has not
      been successful, methadone substitution is improving the medical compliance of
      this difficult clientele, reducing crime and prostitution and, at the same time,
      drug-associated risks for the general population.

PMID- 8300038
TI  - HIV prevalence and risk behaviour in injecting drug users in Berlin.
AB  - In injecting drug users (IDU) newly entering drug treatment centres in Berlin,
      HIV seroprevalence continuously decreased from 1985 through 1992. A recent cross
      sectional study with multi-site sampling (n = 472) showed significantly differing
      HIV prevalences by site of recruitment (treatment centres 6%, storefront units
      20%, infectious disease clinic 56%). In multivariate analysis, the borrowing of
      syringes in prison was the strongest independent predictor of HIV infection. A
      majority of the IDU have reduced risks of infection. However, current risk
      behaviour is common. Of all IDU, 48% reported the borrowing of syringes within
      the previous 6 months, only 13% had consequently used condoms. Current borrowing
      of syringes was associated with younger age, shorter history of intravenous drug
      use, negative HIV serostatus, and non-participation in methadone maintenance
      programmes. Continued preventive efforts against HIV transmission among IDU are
      needed.

PMID- 8300039
TI  - Preventing the spread of HIV among Australian injecting drug users.
AB  - Control of HIV infection among and from injecting drug users is critical for the
      long-term control of HIV infection in Australia. There is now consistent and
      strong evidence that the prevalence of HIV infection among Australian injecting
      drug users is still low. Recent evidence suggests that Australian injecting drug
      users are reducing injecting behaviour associated with HIV infection. Australian
      adopted harm reduction policies early and implemented a comprehensive range of
      programmes vigorously. These were designed to reduce the spread of HIV infection
      in this population. The most plausible explanation for the low prevalence of HIV
      infection in Australia is the adoption and implementation of these policies and
      programmes, although it is unrealistic to expect that this can be proved in a
      definitive way. Control of HIV infection in Australian injecting drug users
      represents one of the major public health triumphs in this country in the past
      decade and probably reduced the present cumulative number of AIDS cases by 1200,
      AIDS deaths by 800 and expenditure on AIDS by at least $60 million. However,
      recent international experience in this area is alarming. The prevalence of HIV
      infection in injecting drug users in Australia will probably rise in the future.
      Complacency, failure to implement HIV prevention in prisons (including especially
      bleach distribution), continued emphasis on supply reduction drug policy and a
      failure to foster a research capability will ensure that this happens sooner
      rather than later.

PMID- 8300040
TI  - HIV-1 prevalence among drug deaths--a multicenter study.
AB  - Since 1985 several European Institutes of Forensic Medicine have cooperated in a
      multicenter study providing a constant monitoring of HIV-1 prevalence among drug
      related deaths. From 1985 to 1991 the HIV status of 5372 drug-related fatalities
      (4328 males, 1044 females) has been tested. A total of 764 (14%) drug deaths were
      HIV-positive (13% of the males, 21% of the females). In contrast to the steadily
      increasing number of drug-related fatalities the HIV-1 prevalence is decreasing,
      especially in the German cities. Regional differences are obvious. The
      development of the HIV prevalence of drug deaths is comparable with that of the
      still living intravenous drug addicts.

PMID- 8300041
TI  - Harm reduction--a common cause.
AB  - In a field as complex as heroin addiction, controversy is useful in stimulating
      exchange of ideas. An appeal for action, however, based on what we already know
      to be enormously beneficial to addicts and to the general society, must be given
      higher priority than proselytizing for any given approach. We know that narcotic
      addiction takes a terrible toll and that, like alcoholism, we are currently
      unable to cure it. We also know that many addicts desperately seek methadone
      treatment, that many can be helped by it, and that many will die without it. The
      conclusion is clear: methadone treatment, one therapeutic approach among many,
      must be available upon request to all those who want it.

PMID- 8300042
TI  - Differences between the course of the drug addict's HIV infection and that of
      other HIV-infected patients.
AB  - Drug addicts have, in general, a less complicated course of HIV infection than
      homosexual HIV patients. They show fewer opportunistic infections and tumors. But
      this advantage is lost by unnecessary complications due to their psychic
      disorders. Their non-compliance and concealment of signs of disease lead to worse
      outcomes of infections, which could be well-treated or prevented.

PMID- 8300043
TI  - Effects of growth hormone on body fat in adults.
AB  - The interactions between growth hormone (GH) and adipose tissue can be considered
      as a cycle: GH is lipolytic and acts to reduce and redistribute body fat; in
      turn, obesity is characterized by reduced GH output. The effects of GH on adipose
      tissue have been studied in obese, elderly and nonobese GH-deficient adults and
      children. In GH-deficient adults GH treatment appears to lead to net loss of fat
      tissue. However, evidence that GH promotes substantial weight loss in the obese
      is scanty. GH treatment trials in the elderly show significant increases in lean
      body mass and smaller decreases in fat mass. Data must be viewed with caution
      because of the methodological pitfalls inherent in measuring body composition and
      failure to induce net weight loss in the obese.

PMID- 8300044
TI  - Use of recombinant human growth hormone in children with chronic renal
      insufficiency: an update.
AB  - Growth retardation is common in children with chronic renal insufficiency (CRI).
      Now that dialysis and renal transplantation (TX) have become life sustaining,
      permanent stunted growth and adult short stature often occurs. Thus, efforts to
      enhance growth using recombinant human growth hormone (rhGH) have been undertaken
      in three groups of patients: chronic renal failure (CRF) prior to dialysis; end
      stage renal disease (ESRD) on some form of dialysis; and following TX (post-TX)
      in whom growth retardation persists. Our initial study was in CRF. Eleven males,
      ages 2.5-16.3 years, with height standard deviation scores (SDS) of > 2.0 below
      the mean, have been treated with rhGH for 18-48 months. rhGH was started in a
      dose of 0.125 mg/kg three times a week in the first 8 patients and subsequently
      changed to daily dosing (0.053 mg/kg/day) within the first 24 months. To date,
      overall, growth velocity (GV) increased from 5.4 +/- 2.2 to 8.9 +/- 1.6, 7.5 +/-
      1.8, 7.5 +/- 1.6 and 6.9 +/- 0.9 cm/year in those completing 12 (n = 11), 24 (n =
      9), 36 (n = 7), and 48 (n = 3) months. The mean height SDS increased from > 3.0
      to < 1.5 below the mean with 1 patient reaching the 50th centile. Dialysis was
      initiated in 2 patients, a frequency not different from that expected over time
      in children with this degree of CRF. In the others, calculated creatinine
      clearance did not change, and no significant adverse effects were noted as a
      consequence of the rhGH treatment. Thus, rhGH increases GV and facilitates catch
      up growth in CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300045
TI  - Body fat in Laron syndrome patients: effect of insulin-like growth factor I
      treatment.
AB  - Changes in body fat mass were studied in 25 untreated patients with Laron
      syndrome from childhood into adulthood. It was found that these patients,
      characterized by marked dwarfism, high plasma hGH and low serum insulin-like
      growth factor I (IGF-I), develop progressive and marked obesity and have a
      tendency for elevated serum cholesterol levels. Long-term treatment of 8 children
      and 5 adults with this syndrome with IGF-I (50-150 micrograms/kg/day s.c.)
      resulted in a significant decrease in subcutaneous fat in all patients and a
      lowering of the serum cholesterol and triglycerides, mainly in the adults. As in
      Laron syndrome the GH receptors are inactive, it is hypothesized that IGF-I
      exerts a direct effect on adipose tissue metabolism.

PMID- 8300046
TI  - The effect of simple obesity on growth and growth hormone.
AB  - Simple obesity is characterized by a normal or increased growth rate with an
      acceleration of bone age maturation. When longitudinal growth slows down in the
      presence of obesity, a hormonal disturbance should be sought. Despite normal
      growth, simple obesity is characterized by a reduced GH secretion evaluated by
      standard provocative tests, the administration of GH-releasing hormone or
      spontaneous 24-hour secretion. In obese children GH secretion may be as low as in
      poorly growing children with classical GH deficiency. The endocrine abnormalities
      along the GH axis seem to involve complex mechanisms at the hypothalamic,
      pituitary and peripheral level. Recent data suggest that simple obesity is
      associated with an increase in GH clearance and a decrease in GH synthesis and
      secretion. It is also associated with high insulin and insulin-like growth factor
      I levels which may interfere in the complex endocrine interactions. In
      conclusion, simple obesity is characterized by normal growth in the presence of
      'hyposomatotropism'.

PMID- 8300047
TI  - Growth hormone effects on carbohydrate and lipid metabolism in childhood.
AB  - The effects of recombinant growth hormone (GH) at therapeutic doses were
      investigated in GH-deficient and nondeficient children with short stature, with
      respect to glucose turnover and insulin sensitivity. In both groups of patients,
      these parameters were normal after 6-12 months of recombinant GH administration.

PMID- 8300048
TI  - Insulin sensitivity and insulin resistance in growth-hormone-deficient adults.

PMID- 8300049
TI  - Normal control of growth hormone secretion.
AB  - Growth hormone (GH) is secreted by the anterior pituitary gland in a pulsatile
      fashion under the regulation of two hypothalamic peptides: GH-releasing hormone
      (GHRH) stimulates GH synthesis and secretion while somatostatin inhibits GH
      release. Studies in rats, sheep and humans indicate that whereas GHRH is required
      for the initiation of GH pulses, the amplitude of GH pulses is modulated by
      somatostatin. In humans, these interactions result in a pattern of volleys of GH
      secretory pulses with intervening periods of relative secretory quiescence. The
      amplitude and frequency of GH-secretory pulses are regulated by a complex array
      of external and internal stimuli including age, gender, menstrual cycle phase,
      pubertal status, nutrition, sleep, body composition and exercise. Changes in
      plasma concentrations of gonadal hormones, insulin and insulin-like growth factor
      I likely mediate the effects of several of these factors. A greater understanding
      of the physiology of GH secretion will enable the development of future
      strategies to enhance GH secretion in GH-deficient states including the use of GH
      secretagogues and modification of nutrition and exercise habits.

PMID- 8300050
TI  - Body fat in GH-deficient children and the effect of treatment.
AB  - Children with isolated GH deficiency have enlarged fat depots due to increased
      fat cell volume. The fat cell number is however decreased compared with
      appropriate controls. Treatment of patients with GH results in a relative loss of
      body fat and shifts both fat cell number and fat cell volume towards normal.
      These findings of adipose tissue cellularity in GH-deficient children before and
      after treatment can be explained by results from in vitro studies indicating that
      GH exerts a variety of effects on the metabolism of mature fat cells and on the
      proliferation and differentiation of cultured preadipocytes. Therefore, GH is one
      of the factors that determines adipose tissue development during childhood.

PMID- 8300051
TI  - Genetics of growth hormone gene expression.
AB  - The regulation of pituitary GH gene expression depends on binding of
      transcriptional activation proteins to cis-active DNA sequences preceding the GH
      1 gene. The POU homeodomain protein Pit-1 is found in the nuclei of somatotrophs,
      lactotrophs and thyrotrophs. It fosters differentiation of these pituitary cell
      types and is required for hormone production by mature cells. In theory, defects
      in GH secretion can be caused by mutations in the GH-1 promoter sequence or in
      the gene encoding Pit-1. In the former case, deficiency would be limited to GH,
      and in the latter deficiencies extend to prolactin (Prl) and thyrotropin (TSH) as
      well as to GH. Both the Pit-1 gene and the GH-1 gene have been examined in
      children with extreme growth failure. Studies of kindreds with GH, Prl and TSH
      deficiency have disclosed a variety of mutations in the Pit-1 gene. These include
      nonsense mutations, missense mutations that diminish binding and transcriptional
      activation, and also mutations that appear to increase promoter binding while
      eliminating transcriptional activation. This latter class of mutation exerts a
      dominant negative effect in vivo as well as in vitro. There are many examples of
      deletions in the GH-1 coding sequence. Some are very large and cause the loss of
      GH-1, chorionic somatomammotropin and placental GH genes. Others are very small,
      involving only 1 or 2 bases. They produce frameshifts and premature stop signals.
      All types produce complete deficiency of GH, but antibody development during
      treatment has proven to be quite variable. The cDNA for the GH-releasing hormone
      receptor has recently been cloned and sequenced.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300052
TI  - Use of growth hormone and insulin-like growth factor I in catabolism that is
      induced by negative energy balance.
AB  - Both GH and insulin-like growth factor I (IGF-I) have been shown to promote
      anabolism in human volunteers that are made catabolic by caloric restriction. We
      have used caloric restriction as a model of controlled catabolism to test the
      efficacy of these agents in reversing negative nitrogen balance. Six normal
      volunteers underwent caloric restriction for 2-week intervals. This restriction
      induced negative nitrogen balance (e.g. -239 mmol/day). During the second week
      either IGF-I (16 micrograms/kg h) was administered by intravenous infusion for 16
      h, or GH (0.05 mg/kg) was given subcutaneously daily. GH alone improved nitrogen
      balance by 180 mmol/day, and IGF-I improved it by 175 mmol. The two hormones had
      opposite effects on carbohydrate metabolism. Mean blood glucose rose
      approximately 26% with GH whereas it fell 37% with IGF-I and the subjects had
      frequent hypoglycemic episodes during the infusion. Minimal complications were
      observed during the 6 days of IGF-I infusion and consisted primarily of edema and
      jaw pain. It appeared that IGF-I was as efficacious as GH in reversing the
      negative nitrogen balance induced by caloric restriction and that hypoglycemia
      induced by IGF-I was the major limiting factor. In a second study 7 volunteers
      underwent the identical caloric restriction. In contrast to the first study one
      treatment group received the combination of GH plus IGF-I given in exactly the
      same doses as in the first study. A second group received IGF-I alone. The
      combination of GH/IGF-I was much more potent in improving nitrogen
      balance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300053
TI  - Growth hormone and diabetes mellitus. A review of sixty-three years of medical
      research and a glimpse into the future?
AB  - The diabetogenic action of pituitary extracts containing growth hormone has been
      recognised for more than 60 years and the importance of growth hormone in the
      development and progression of diabetic retinopathy for more than 30 years.
      Hypophysectomy was the first effective treatment for retinopathy but was
      discontinued because of the risk of severe hypoglycaemia that it produced and the
      development of an alternative, less dangerous therapy--photocoagulation. The
      precise role and significance of growth hormone in diabetes care, however,
      remains to this day a mystery. The fact that modern, highly purified biosynthetic
      preparations of growth hormone still retain full diabetogenic potency and the
      fact that diabetes develops in up to 25% of patients with acromegaly indicate
      growth hormone's potential for involvement in the aetiology of diabetes mellitus,
      although most will agree that this is not likely to be an important factor in the
      large majority of 'idiopathic' cases. There is strong evidence to indicate a
      substantial hypersecretion of growth hormone in 'idiopathic' diabetes mellitus
      (particularly insulin-dependent cases and those with retinopathy), which appears
      to be more related to residual pancreatic insulin secretion than to metabolic
      control. Since the advent of biosynthetic growth hormone in sufficient quantity
      to perform trials in adults, we are more aware of growth hormone's considerable
      potency in the regulation of body composition, growth factor production and
      intermediary metabolism. In this article, we review the literature and, from this
      and our own work, propose a new hypothesis which links the hypersecretion of
      growth hormone to reduced hepatic secretion of insulin-like growth-factor I (IGF
      I) as a direct result of reduced portal insulin levels in diabetes mellitus. The
      hypersecretion of growth hormone exposes peripheral organs such as the retina and
      kidney to conditions favouring the expression of growth-hormone-dependent growth
      factors such as IGF-I which may contribute to the development of diabetic
      microvascular disease by autocrine and/or paracrine effects. If this hypothesis
      proves to be true, it offers new opportunities for the prevention of diabetic
      microvascular complications through suppression of growth hormone secretion which
      in turn will increase insulin sensitivity and facilitate good glycaemic control.

PMID- 8300054
TI  - Aging and growth hormone.
AB  - Detailed studies of the ontogeny of growth hormone (GH) secretion have shown
      unequivocally that GH is produced throughout life but secretion declines
      progressively to about 20% of that in puberty. These changes are accounted for in
      part by changes in central neuro-endocrine function, nutritional factors and by
      changes in sex steroid milieu. Mean 24-hour GH concentrations in the normal
      elderly are frequently below the limit of assay detectability where values are
      indistinguishable from matched adults with organic GH deficiency. The notion that
      diminished GH action may account for the undesirable changes in body composition
      and function in the elderly is supported by beneficial findings of GH treatment
      in GH-deficient adults. Preliminary results of GH treatment in the normal elderly
      suggest beneficial effects on body composition but a high incidence of side
      effects. Questions addressing cost, benefit, dosage, safety and tolerance need to
      be critically addressed before GH can be considered for use in the aging.

PMID- 8300055
TI  - Effect of human growth hormone and insulin-like growth factor I on whole-body
      leucine and estimates of protein metabolism.
AB  - Recombinant human growth hormone (rhGH) administration to normal volunteers
      increases estimates of whole-body and forearm protein synthesis but has little
      effect on rates of proteolysis in both the postabsorptive state and during meal
      absorption. In contrast, insulin decreases estimates of whole-body and forearm
      proteolysis while decreasing or, in the presence of infused (or ingested) amino
      acids, sustaining estimates of protein synthesis. We have used high-dose
      prednisone as a controlled model for protein catabolism in normal volunteers and
      demonstrated that glucocorticosteroids increase estimates of whole-body
      proteolysis and the oxidation of leucine with little or no effect on estimates of
      whole-body protein synthesis. We have recently demonstrated that high-dose rhGH
      together with prednisone prevents the protein-catabolic effects observed with
      treatment with prednisone alone, while inducing insulin resistance and increased
      secretion of proinsulin. GH is thought to mediate its effects via the generation
      of insulin-like growth factor I (IGF-I). However, high rates of infusion of rhIGF
      I induce hypoglycemia and decrease estimates of whole-body proteolysis and
      suppress the secretion of GH, insulin and glucagon, suggesting a predominant
      insulin-like effect on protein and glucose metabolism. When rhIGF-I is infused at
      a rate that achieves plasma IGF-I concentrations similar to those observed during
      rhGH treatment and yet avoids hypoglycemia, estimates of proteolysis and protein
      synthesis were not affected in the absence or presence of prednisone treatment.
      When rhGH and rhIGF-I are administered simultaneously, nitrogen balance is
      remarkably improved. Thus, the mechanism of action of both rhGH and/or rhIGF-I on
      body protein metabolism remains to be elucidated.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8300056
TI  - Growth hormone and insulin-like growth factors as anabolic therapies for
      osteoporosis.
AB  - Growth hormone (GH) and insulin-like growth factors (IGFs) play a central role in
      skeletal growth and bone remodeling. In vitro, both agents display anabolic
      properties, and patients with acromegaly exhibit increased bone mass. Recent in
      vivo studies have demonstrated profound activation of bone remodeling that lasted
      for months after a single 1-week dose of GH or IGF-I. Despite these positive
      effects, the few clinical studies conducted with GH in osteoporotic patients have
      shown disappointing results in terms of bone mass changes. Changes in dosing
      regimens and other adjuvant therapies may, however, lead to more efficient use of
      these agents.

PMID- 8300057
TI  - Growth hormone and surgery.
AB  - Growth hormone (GH) is a very potent anabolic agent released in the physiological
      situation in a pulsative manner from the pituitary gland. GH stimulates the
      protein synthesis and increases the intracellular transport of amino acids. When
      GH is administered to surgical patients, nitrogen retention is regularly seen,
      and in most situations fast mobilization takes place. The present data indicate
      that GH has a beneficial effect on the healing processes after surgery and
      trauma.

PMID- 8300058
TI  - Improved method for predicting adult height of pubertal boys using a mathematical
      model.
AB  - Several methods for adult height prediction are currently in use. All are subject
      to a wide range of error which is thought to result, at least in part, from the
      use of bone age estimation. Following the suggestion made by Karlberg to predict
      adult height of pubertal children by the use of the 'Infancy-Childhood-Puberty
      model' (ICP), growth data of 39 normal boys who were followed from infancy until
      adult height was attained were reviewed. Use of the ICP model alone and without
      bone age resulted in more accurate predictions of adult height than those made by
      the methods which required bone age determination, the Bayley-Pinneu (BP) and the
      Tanner-Whitehouse methods (TW). The absolute error of prediction was 3.4 cm as
      compared to 5.3 (BP) and 4.9 cm (TW) (p < 0.05) and maximal range of error was 10
      cm as compared to 22 (BP) and 21 cm (TW) (p < 0.05). Finally, based on the ICP
      model, a new equation which incorporates paternal height was been derived. This
      equation, termed ICP-New (ICPN), resulted in even better accuracy: absolute error
      of prediction was 2.3 cm as compared to 3.4 cm (ICP) and maximal range of error
      was 6 cm as compared to 10 cm (ICP) (p < 0.05). It is concluded that the ICP
      model and the ICPN equation may predict the adult height of pubertal boys more
      accurately than the methods which use bone age.

PMID- 8300059
TI  - Growth response to growth hormone during the first year as a diagnosis criterion
      of growth hormone deficiency.
AB  - Idiopathic growth hormone (GH) deficiency is a clinically and biologically
      heterogeneous condition. This study evaluates the capacity of the initial growth
      response to hGH therapy to distinguish certain from transient GH deficiency.
      Twenty-five patients having a GH peak < 10 micrograms/l after 2 pharmacological
      stimulation tests were classified according to the accuracy of the diagnosis of
      GH deficiency. Group 1 (n = 17) had certain GH deficiency because of pituitary
      stalk interruption syndrome and/or familial form. Group 2 (n = 8) had a transient
      GH deficiency. The mean increase in height standard deviation (SD) was 1.3 +/-
      0.1 (mean +/- SE) and 0.5 +/- 0.1 during the first and second years in group 1
      and 0.4 +/- 0.1 (p < 0.0005, compared to group 1) and 0.1 +/- 0.2 (p < 0.025
      compared to group 1) during the first and second years in group 2. During the
      first year of therapy, the increase in height was > or = 1 SD in 14 patients of
      group 1 and in 1 patient of group 2. In group 1, this increase was positively
      correlated with an increase in body mass index (r = 0.80, p < 0.01) during the
      first year and with target height (r = 0.60, p < 0.02) during the second year.
      Growth rate (SD for age) during the first year in this group was negatively
      correlated with the height prior to therapy (r = -0.72, p < 0.005).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8300060
TI  - Coping and satisfaction with growth hormone treatment among short-stature
      children.
AB  - The ability of children to cope with a chronic medical problem requiring
      prolonged treatment has an effect on the quality of life of these children and of
      their parents and serves as an index of the quality of treatment. This study
      deals with coping ability and satisfaction with treatment of children whose
      stature was two or more SD below the average for age and gender. The study
      population included 96 patients, 53 of whom were male, who were on growth hormone
      (GH) treatment for at least 1 year. 65 patients were without any underlying
      disease, 15 had classical GH deficiency and 16 had Turner syndrome or renal
      disease. All patients were treated with daily injections at home from 12 to 66
      months. Using a self-administered questionnaire, the ability to cope and the
      degree of satisfaction and compliance with treatment were assessed. No
      significant differences were found with respect to gender, the presence of an
      underlying disease, age at which treatment commenced or duration of treatment.
      Despite the fact that the outcome of GH treatment on final height has yet to be
      established, satisfaction and compliance were high.

PMID- 8300061
TI  - Idiopathic prepubertal short stature is associated with low body mass index.
AB  - The hypothesis that insufficient body weight is partly responsible for idiopathic
      short stature was tested by evaluating 79 prepubertal children having idiopathic
      short stature, classified according to their body mass index (BMI) zs: group 1
      BMI zs < or = 0 (m +/- SE, -0.9 +/- 0.1, n = 53) and group 2 BMI zs > 0 (0.6 +/-
      0.1, n = 26). Their ages were similar (8.1 +/- 0.3 and 8.4 +/- 0.4 years). The
      following parameters were significantly lower in group 1 than in group 2: height
      (-2.5 +/- 0.1 vs. -2.2 +/- 0.1 SD, p < 0.05), height velocity (-1.5 +/- 0.2 vs. 
      0.9 +/- 0.4 SD, p < 0.05), bone age (bone age retardation 2.3 +/- 0.2 vs. 1.3 +/-
      0.4 years, p < 0.005) and plasma insulin-like growth factor 1 (IGF-1, 0.8 +/- 0.1
      vs. 1.2 +/- 0.1 U/ml, p < 0.05). The BMI was significantly lower in children with
      idiopathic short stature (-0.4 +/- 0.1) than in the normal population (zs, p <
      0.0002). BMI zs was positively correlated with height (p < 0.005), height
      velocity (p < 0.05) and plasma IGF-1 (p < 0.01). We conclude that children with
      idiopathic short stature are leaner than the normal population. An inadequate or
      insufficient nutritional intake may be partly responsible for idiopathic short
      stature. The effects of improved intake on the height change are under
      evaluation.

PMID- 8300062
TI  - Gonadotropin-associated psychosis in perimenstrual behavior disorder.
AB  - Sexually provocative and violent behavior have been reported as a result of
      excess androgens. We now report a temporal relationship between increased
      gonadotropin levels and behavioral changes in two adolescent girls who presented
      with a history of aggressive and bizarre sexual behavior coincident with the
      onset of menarche. We evaluated the possibility of a cyclical hormonal cause with
      daily measurements of gonadotropins, androgens and estradiol levels and
      correlated the results with periodic reports on the girls' behavior. We concluded
      that a correlation exists between periods of extremely violent and sexually
      provocative behavior and peaks of gonadotropin hormone secretion, even though
      androgen levels were normal. Treatment with medroxyprogesterone acetate (Depo
      Provera) in one case and with leuprolide acetate (Lupron-Depot) in the other
      suppressed gonadotropin levels, and behavior improved markedly. Thus, the
      behavioral changes (or psychosis) seen in these girls might have been induced by
      increased levels of gonadotropins.

PMID- 8300063
TI  - Deficiency of 17-ketoreductase presenting before puberty.
AB  - The diagnosis of 17-ketoreductase deficiency is established in most patients at
      or after puberty when basal plasma androstenedione levels are high; data on
      prepubertal children are limited. Two infants with external female genitalia
      presented in infancy with inguinal herniae and palpable gonads. Both had a 46,XY
      karyotype, a short vagina, absent uterus, and a gonadal biopsy showing testicular
      tissue. The value of an hCG stimulation test in making the diagnosis of 17
      ketoreductase deficiency was confirmed by a minimal plasma testosterone but
      marked androstenedione response. Androgen receptor deficiency based on studies in
      genital skin fibroblasts was demonstrated in one of the cases. We speculate that
      this is possibly the result of failed induction of receptors secondary to
      androgen deficiency. Though 'tomboyish' in behaviour, both children are reared as
      girls.

PMID- 8300064
TI  - Effect of octreotide on catecholamine plasma levels in patients with chromaffin
      cell tumors.
AB  - Many chromaffin cell tumors contain somatostatin (SS), and most of them are
      receptor-positive by in vitro autoradiography and by in vivo administration of
      radiolabeled SS analogs. We evaluated the effect of a 2-hour infusion of 50
      micrograms octreotide on plasma norepinephrine (NE) and epinephrine (E) levels in
      6 patients with chromaffin cell tumors. To ascertain the biological activity of
      octreotide, plasma insulin levels were also measured. Infusion of octreotide was
      followed in all the patients but 1 by a progressive decrease of plasma NE levels.
      On the average, plasma NE decreased significantly during octreotide
      administration, halving its baseline levels at the end of the infusion (51.3 +/-
      11.46%, p < 0.05) and rising again slowly thereafter. A slight reduction of
      plasma E levels was also recorded at the end of octreotide infusion (76.1 +/-
      13.77% of baseline, NS) with a prompt return of hormone concentrations to
      preinfusion values. During octreotide administration, plasma insulin displayed an
      early and steep fall (49.7 +/- 4.61% of baseline, p < 0.03, at 60 min) with a
      tendency to escape from inhibition before termination of the infusion. In 5/6
      patients, 2 of whom were normotensive before the study and 1 the day of the test,
      blood pressure did not change during octreotide infusion. In the other patient,
      blood pressure fell from baseline values of 160/100 to 120/70 mm Hg at 120 min
      and rebounded to 205/100 mm Hg at 240 min. In conclusion, the short-term
      administration of low-dose octreotide is capable of lowering NE levels, though
      with no consistent effect on blood pressure, in patients with chromaffin cell
      tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300065
TI  - Non-neoplastic, cutaneous and mucocutaneous manifestations of HIV infection.

PMID- 8300066
TI  - The importance of a substantial elastic lamina subjacent to the endothelium in
      limiting the progression of atherosclerotic changes.
AB  - This study examines the hypothesis that progressive intimal thickening and
      atherosclerosis in the larger pulsatile arteries arise from failure to maintain,
      subjacent to the endothelial cells, a substantial elastin membrane, a component
      which has been shown to be of special structural significance. The internal
      thoracic arteries of 293 subjects of all ages up to 60 years were compared
      histologically with the anterior descending coronary arteries of the same
      individuals by light- and electronmicroscopy and immunoperoxidase staining for
      macromolecules. The internal thoracic arteries usually developed a new robust
      reduplicated internal elastic lamina at an early age, no further intimal
      thickening, and no significant entry of lipid or cells to the intima. The
      coronary arteries showed areas of rapid intimal thickening with poor and
      incomplete reduplicated internal elastic laminae, entry of lipid, macrophages,
      and other cells to the intima. The reduplicated internal elastic laminae appeared
      to be formed primarily by the endothelial cells themselves. An elastin membrane
      subjacent to the endothelial cells appears to be essential. It provides a secure
      attachment for the cells and a barrier to the entry of macromolecules and cells
      to the intima. Its absence is associated with progressive intimal thickening and
      atherosclerosis.

PMID- 8300067
TI  - Occult thyroid carcinomas in the region of Minsk, Belarus. An autopsy study of
      215 patients.
AB  - Thyroid glands from 215 patients, aged 19 to 88 years, without known thyroid
      disease, were serially sectioned at 2-3 mm intervals and microscopically examined
      for occult disease. Glands were normal in 32.5%, while nodules were observed in
      60% and adenomas in 13%. Carcinomas were found in 20 cases (9.3%): occult
      papillary carcinomas in 19 (8.8%) and one medullary carcinoma. No carcinomas were
      found in the thyroids of 15 patients less than 40 years of age. There were no
      significant differences in frequency of occult carcinomas between female and male
      patients and, for patients over 40 years, with increasing age. Of the 19
      papillary tumours more than one focus was found in six cases (a total of 28
      foci). The diameter of 27 of these tumours was less than or equal to 5 mm
      (96.4%), with one exception (diameter 6.3 mm). These findings were compared with
      those obtained in 86 thyroid glands of children surgically resected for
      carcinomas between 1986 and 1991. Only 10 of these tumours (11.6%) were less than
      or equal to 1 cm. These tumours, however, were significantly larger than the
      occult papillary carcinomas and their morphological features were quite
      different. Our results are discussed with regard to the possible role of factors
      other than irradiation due to the nuclear accident at Chernobyl, and the observed
      sharp numerical increase of thyroid carcinomas in children of the Republic of
      Belarus after this event.

PMID- 8300068
TI  - The prognostic significance of the DNA content in Ewing's sarcoma: a
      retrospective cytophotometric and flow cytometric study.
AB  - The DNA content of the cell nuclei of Ewing's sarcoma was analysed by means of
      cytophotometry in situ with image analysis in Feulgen-stained sections in 37
      patients, and by retrospective flow cytometry according to the method of Hedley
      in 26 patients. Different histogram patterns were obtained: normal unimodal or
      bimodal DNA distributions and abnormal DNA distributions with one or two stem
      lines, or an abnormal DNA distribution with no stem lines. Both methods enabled
      us to make a distinction between two groups of Ewing's sarcomas with a different
      prognosis. All patients with aneuploid tumours died within 5 years after the
      initial diagnosis. Eleven of 19 (58%) patients with a normal DNA distribution in
      their tumour, as determined by cytophotometry, are still alive and in good health
      with a mean survival period of 7.5 years, ranging from 2 to 19 years. Of the
      group of patients in which flow cytometry revealed a normal DNA pattern, eight of
      15 (53%) are still alive and in good health, with a mean survival period of 8
      years. These results indicate that both techniques are reliable methods for
      obtaining prognostic information in Ewing's sarcomas. However, cytophotometry in
      situ yielded a better discrimination for the overall survival (P < 0.01) than did
      flow cytometry (P < 0.05). In 19% of the cases there was a discrepancy between
      the DNA histograms obtained with the two techniques. In five of 26 cases the DNA
      distributions were classified as normal by one method and aneuploid by the other.
      Tumour cell representation or selective loss of cells during enzymatic treatment
      may be responsible for this discrepancy.

PMID- 8300069
TI  - Gastritis in patients on non-steroidal anti-inflammatory drugs.
AB  - This study investigated the spectrum of gastric mucosal pathology, including the
      prevalence of reactive gastritis in patients on non-steroidal anti-inflammatory
      drugs (NSAIDs). The histological findings were correlated with upper
      gastrointestinal symptom status and endoscopic findings and were also compared
      with the histological appearances of the gastric mucosa in a corresponding age
      matched control group of 75 patients not receiving NSAIDs or any other drug
      therapy. Reactive gastritis of the gastric antrum was more common in the NSAID
      group and was observed in 34 patients (45.3%), as an isolated phenomenon in 24
      patients (32%) and with evidence of coexistent chronic gastritis in 10 patients
      (13.3%). In the control group reactive gastritis of the antrum was seen in 10
      patients (13.3%), as an isolated finding in eight cases (10.7%) and with
      accompanying chronic gastritis in two cases. Chronic antral gastritis of usual
      type was observed in 36 patients on NSAIDs (48%) and Helicobacter-like organisms
      were identified histologically in 18 of these (50% carriage rate). These
      organisms were not seen in any of the patients in whom the picture of reactive
      gastritis was present. In the control group chronic antral gastritis was seen in
      51 patients (68%) with organisms in 34 (66.6% carriage rate). No correlation was
      found between the presence or absence of upper gastrointestinal symptoms,
      endoscopic findings and the histological appearances of the gastric mucosa. We
      conclude that NSAIDs are an independent cause of reactive gastritis in the antrum
      and do not appear to alter gastric mucosal colonization by Helicobacter-like
      organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300070
TI  - Atypical and malignant meningiomas: importance of micronecrosis as a prognostic
      indicator.
AB  - Twenty-eight patients with a diagnosis of either atypical or malignant
      meningioma, according to the World Health Organisation (WHO) classification, were
      followed up to relate histopathological features with times to recurrence and
      death. Five year disease-free survival was 41% with a median disease free
      survival of 27 months. Micronecrosis was the only histopathological feature
      associated with increased risk of recurrence (rate ratio, 3.73: 95% confidence
      interval 1.03-13.6). At 36 months, 32% of patients with micronecrosis were alive
      compared with 71% of patients without micronecrosis. Brain invasion was not
      associated with disease-free survival. After recurrence, median survival was 7
      months and was not correlated with any histopathological feature. The prevalence
      of micronecrosis was estimated from random samples of benign, atypical and
      malignant meningiomas to be 8%, 42% and 71% respectively. The relevance of these
      findings and the current WHO classification is discussed.

PMID- 8300071
TI  - Myxoma of the maxillary antrum in children.
AB  - Myxomas of the maxillary antrum are rare tumours, particularly in childhood.
      Although circumscribed, they are often more extensive than apparent and so tend
      to recur despite their benign nature. Myxomas are gelatinous and are composed of
      stellate and spindle cells embedded in an abundant alcian blue-positive, mucoid
      stroma in which blood vessels are often scattered throughout the tumour. Three
      patients with maxillary myxomas, all presenting in infancy or early childhood,
      are described.

PMID- 8300072
TI  - Intestinal metaplasia in stilboestrol-induced vaginal adenosis.
AB  - We present an unusual case of vaginal adenosis with progressive intestinal
      metaplasia, previously undescribed, in a female patient exposed to stilboestrol
      in utero. Argentaffin cells were present within these areas, a feature not
      previously reported in benign vaginal adenosis. The development of the intestinal
      metaplasia coincided with the onset of a vaginal discharge so severe that, after
      7 years, a vaginal resection was performed. Intestinal-type glands have been
      described in the cervix and ovary, almost invariably associated with malignancy.
      The possible role of intestinal metaplasia in the development of enteric-type
      neoplasms of the vagina is discussed.

PMID- 8300073
TI  - Antigen retrieval by microwave irradiation lowers immunohistological detection
      thresholds.

PMID- 8300074
TI  - Breast carcinoma occurring in association with silicone augmentation.

PMID- 8300075
TI  - Acinic cell carcinoma of the sinonasal cavity with intracytoplasmic crystalloids.

PMID- 8300076
TI  - Radiation-induced thyroid cancer.

PMID- 8300077
TI  - Ectopic parathyroid within a ganglion, not a paraganglion.

PMID- 8300078
TI  - Primary leiomyomatosis of lymph node or nodal lymphangiomyoma?

PMID- 8300079
TI  - Vascular lesions in Crohn's disease.

PMID- 8300080
TI  - Genetic epidemiology of colon cancer in the cotton-top tamarin (Saguinus
      oedipus).
AB  - Colon cancer is known to be heritable in humans, but the opportunity to
      investigate the genetic epidemiology of cancer in nonhuman primates has been
      limited by the size of available populations. The cotton-top tamarin (Saguinus
      oedipus) colony at the Oak Ridge Associated Universities (ORAU) Marmoset Research
      Center is a large population with a high rate of spontaneous colon cancer that
      has been monitored over several years, thus allowing investigation of the genetic
      basis for colon cancer in this colony. The presence of colon cancer at death was
      scored in 392 necropsies at the colony. Genealogical and demographic data for
      these animals were obtained from colony records. The heritability of the
      liability to colon cancer was estimated using maximum-likelihood-based pedigree
      analyses after evaluating the effects of gender, origin (wild-born or laboratory
      born), and age at death on cancer experience. Cancer rates were not significantly
      different between males and females or between wild- and laboratory-born animals.
      Differences in age at death were also statistically insignificant for both
      laboratory- and wild-born animals. The heritability estimate for the liability to
      contract colon cancer is 17% for the ORAU cotton-top tamarins. This heritability
      estimate is not significantly different from zero, indicating no evidence for
      heritable variation in cancer experience in this population. If genetic factors
      affect cotton-top tamarin colon cancer, they are fixed or nearly fixed in this
      population.

PMID- 8300081
TI  - Genetic analysis of hematological traits in chimpanzees (Pan troglodytes).
AB  - Hematological traits are commonly assessed markers of health status that have
      been used in a large number of anthropological studies, especially those focusing
      on high-altitude adaptation. Despite the wealth of literature on environment
      associated variation in these traits, relatively few studies have dealt with the
      underlying genetic components of hematological measures. The purpose of this
      study is to estimate heritabilities for eight hematological traits using data
      obtained from a large pedigreed chimpanzee colony. Seven of the eight
      hematological traits exhibited significant heritabilities, ranging from h2 =
      0.308 for mean cell volume to h2 = 0.834 for red blood cell count. The use of
      multiple measures per individual proved to be essential for the accurate
      estimation of heritabilities. We conclude that the underlying genetic variation
      in hematological traits should be considered when these measures are used in
      study protocols.

PMID- 8300082
TI  - The anthropological perspective in genetic epidemiology.

PMID- 8300083
TI  - Genetic-epidemiological methods in anthropological research.

PMID- 8300084
TI  - Determination of relatedness between individuals using DNA fingerprinting.
AB  - Relatedness between individuals is an important element of genetic
      epidemiological and evolutionary investigations in the context of anthropological
      research. In general, data on relationships between individuals are gathered from
      personal interviews or from examination of vital records. When blood samples are
      collected, such information can be validated from genotypic similarities of
      individuals. Although genotype data may offer opportunities to exclude certain
      types of relationships, inclusionary statements are necessarily only
      probabilistic in nature. The limitations of such probabilistic statements depend
      on the number of segregating alleles and the extent of polymorphisms at the loci
      employed. With the advent of DNA technology, several hypervariable single-locus
      probes (SLPs) and multilocus probes (MLPs) are now available for many organisms.
      These can be used to circumvent limitations of unequivocal assignment of
      relationships from genotype data. In this article we describe analytical
      principles for such investigations. In particular, we propose summary measures of
      DNA fingerprinting data (e.g., number of different alleles and number of shared
      alleles) that can be used to describe kinship relationships between individuals.
      We derive the expected distributions of number of alleles in individuals and of
      number of shared alleles between individuals of known relationships in a
      population. These distributions can be used in hypothesis testing to determine
      relatedness between individuals. We also derive the number of SLPs, each
      detecting a hypervariable polymorphism, needed to determine a specified
      relationship for given ranges of errors of prediction. Illustrations of the
      theory with data on several short tandem repeat loci and variable number of
      tandem repeat (VNTR) loci indicate that with 6 to 12 SLPs the parent-offspring
      pairs can be reliably distinguished from random pairs of individuals. This theory
      also serves the purpose of detecting inbreeding levels in a natural population.

PMID- 8300085
TI  - Multivariate quantitative genetic simulations in anthropology with an example
      from the South Pacific.
AB  - Computer simulation is a commonly used tool both in genetic epidemiology and in
      anthropological genetics. We describe here various methods for simulating
      multivariate quantitative genetic evolution and apply these methods in an
      analysis of craniometrics from two Pacific island samples. The results of this
      application indicate that the two samples (one from the Tolai and one from the
      Moriori) are significantly different, even when allowing for founder effect,
      intense selection on founders, and genetic drift. The simulation methods we
      describe and use are commonly applied in animal breeding studies and are much
      more efficient and general than the multilocus gene-dropping technique usually
      used in anthropological genetics simulations.

PMID- 8300086
TI  - Evolutionary models of quantitative disease risk factors.
AB  - Numerous mutations are now known that have significant effects on various
      phenotypes; many of these mutations are of interest because they influence
      quantitative risk factors for major diseases. Such diversity raises the question
      of how much genetic heterogeneity we should expect to find in the effects of
      alleles, that is, the size of the effects, the number of severe alleles, and
      their frequency in the population. Can evolutionary models suggest a general
      pattern? In this article we examine what is currently known about several basic
      aspects of the problem. These include the distribution of quantitative effects of
      new mutations on a phenotype, the distribution of allelic effects that would be
      found in a natural population, and the relationship between these effects and
      Darwinian fitness. We discuss these issues in light of various models that have
      been proposed and the existing relevant data. Then we consider how these points
      relate to the distribution of genetic effects on an important human trait, the
      cholesterol ratio, an important risk factor for coronary heart disease. The
      complexities of quantitative traits and inadequacies in the available data
      prevent definitive models that can directly connect the mutational effects,
      allelic effects, and fitness distributions from being developed, and we consider
      how sample limitations and the nonequilibrium of human populations caused by our
      demographic history make rigorous solutions difficult. However, based on what is
      currently known, we argue that for human quantitative chronic disease risk
      factors the nearly neutral models of allelic evolution at single loci probably
      apply reasonably well. In general, and although much is still speculative, the
      data available for such risk factors are consistent with these expectations and
      may enable us to predict many aspects of etiologic heterogeneity for human
      disease.

PMID- 8300087
TI  - Statistical genetic approaches to human adaptability.
AB  - The genetic determinants of physiological and developmental responses to
      environmental stress are poorly understood. This has been primarily due to the
      difficulty of direct measurement of response and the lack of appropriate
      statistical genetic methods. Here, I present a unified statistical genetic
      methodology for human adaptability studies that permits evaluation of the
      inheritance of quantitative trait response to environmental stressors. The
      foundation of this approach is the mathematical relationship between genotype
      environment interaction and the genetic variance of response to environmental
      challenge. I describe two basic methods that can be used for either discrete or
      continuous environments. Each method allows for major loci, residual polygenic
      variation, and genotype-environment interaction at both the major genic and the
      polygenic levels. The first method is based on multivariate segregation analysis
      and is appropriate for situations in which data are available for each individual
      in each environment. The second method is appropriate for the more common case
      when response to the environment cannot be observed directly. This method is
      based on an extension of a mixed major locus/variance component model and can be
      used when singly measured related individuals are observed in different
      environments. Three example applications using data on lipoprotein variation in
      pedigreed baboons are provided to show the utility of these methods.

PMID- 8300088
TI  - Obesity: choosing genetic approaches from a mixed menu.
AB  - Obesity, as defined by any number of metrics, aggregates in families but does not
      segregate as a simple Mendelian trait. Because of the frequent association of
      obesity with a number of common chronic diseases, researchers are greatly
      interested in identifying the genes that contribute to obesity and their mode of
      action. The lack of a consensus regarding the biological basis of obesity makes
      the selection of appropriate candidate genes difficult. Several approaches to
      selecting plausible candidate genes for the study of obesity are outlined here.
      The study of rare human phenotypes that result in extreme obesity may identify
      genes that through polymorphic genetic variation may have an effect on body mass,
      body composition, or fat distribution. The study of human genes homologous to the
      mouse genes that lead to obesity in particular strains of inbred mice may also
      give clues to the location and identity of obesity-related genes. Human
      populations in which obesity is particularly prevalent may serve as a substrate
      for identifying such genes in the general population.

PMID- 8300089
TI  - Genetic analysis of patterns of growth in infant recumbent length.
AB  - A genetic basis to growth and development has been demonstrated in many
      heritability studies of anthropometrics. Although such measures describe the
      extent of growth at particular times, they do not fully address the process of
      growth. We applied a three-parameter curve-fitting function to serial measures of
      recumbent length from 569 infants (birth to 2 years of age) in 188 families
      enrolled in the Fels Longitudinal Study. This yielded three growth pattern
      parameters that represented estimated recumbent length at birth (parameter 1),
      rate of growth (parameter 2), and intrinsic rate of change in growth (parameter
      3). The growth pattern parameter estimates for each individual were examined in a
      series of genetic analyses using a maximum-likelihood method for pedigree data.
      Significant heritabilities were found for all three growth pattern parameters:
      parameter 1, h2 = 0.83 +/- 0.12; parameter 2, h2 = 0.67 +/- 0.18; and parameter
      3, h2 = 0.78 +/- 0.17. In addition, genotype by sex interaction was indicated for
      growth pattern parameters 2 and 3, suggesting that the genes influencing rate of
      growth and intrinsic rate of change in growth are themselves influenced by the
      sex of the individual.

PMID- 8300090
TI  - Quantitative genetics of relative organ weight variation in captive baboons.
AB  - Anthropoid phylogeny has been characterized by dramatic increases in relative
      brain size. Given the importance of genetic mechanisms in evolution, quantitative
      genetic analyses of the biological concomitants of relative brain size variation
      should greatly augment our understanding of this phylogenetic phenomenon. In
      humans the brain is often linked metabolically with three other organs--heart,
      kidneys, and liver--that together account for most of the total basal metabolic
      rate. Because the weights of these four organs are proportional to their
      individual organ metabolic rates, their summed weights have been used by previous
      researchers as a proxy measure for their composite organ metabolic rate. We have
      conducted a quantitative genetic analysis of variation in the relative weights of
      these four organs in a population of captive baboons from the Southwest
      Foundation for Biomedical Research. These analyses were performed on loge
      transformed organ weights available for 601 animals, 307 of which were assigned
      to 25 pedigrees containing 2 to 49 members; the remaining 294 animals were
      treated as independent individuals. Moderate but statistically significant (p <
      0.005) heritabilities were estimated for all four organ weights: h2brain = 0.409
      +/- 0.147, h2heart = 0.386 +/- 0.184, h2kidneys = 0.468 +/- 0.152, and h2liver =
      0.600 +/- 0.160. Significant (p < 0.05) additive genetic correlations were
      estimated between brain and liver weights (rho G = 0.568) and between liver and
      kidney weights (rho G = 0.858). Significant (p < 0.05) environmental correlations
      were identified for heart and kidney weights (rho E = 0.551) and for liver and
      kidney weights (rho E = 0.684). Our results clearly demonstrate that the four
      organ weights have substantial heritable components that, because of their
      similar magnitudes, are probably equally susceptible to selection. However, the
      patterns of intercorrelation revealed by our analyses of the genetic and
      environmental correlation matrices indicate that, of the four organs composing
      the proxy measure of organ metabolic rate, only the liver and the kidneys are
      likely to exhibit correlated responses to selection for increased relative brain
      size such as that observed in the anthropoid fossil record.

PMID- 8300091
TI  - The diagnosis and treatment of urethritis in developing countries.

PMID- 8300092
TI  - Casual sexual experience abroad in patients attending an STD clinic and at high
      risk for HIV infection.
AB  - OBJECTIVE: To study possible "import" routes of HIV infection to Norway (by
      obtaining information on casual sexual contacts abroad from patients attending an
      STD clinic), and to assess their behavioural risk factors (such as alcohol
      intake, use of condom) for HIV infection. DESIGN AND SETTING: Patients visiting
      the clinic for sexually transmitted diseases (STD), April-June 1989, received a
      questionnaire. SUBJECTS: 606 consecutive persons of whom 599 agreed (98.8%) to
      participate. We grouped the patients in four categories. 1: Sex with a prostitute
      during the last 5 years, 2: Homosexuals/bisexuals, 3: prostitutes/intravenous
      drug abusers (IVDUs) and 4: Other heterosexuals. RESULTS: 245 patients (41%)
      reported having a casual sex partner abroad (M: 182, F: 63), mainly in Europe,
      particularly in Spain, Denmark and Greece. Outside Europe such contacts were most
      frequently reported from USA, Brazil and Thailand. Among men who had had sex with
      a prostitute, 93.5% reported such sex abroad (homosexuals/bisexuals: 63.6%,
      prostitutes/IVDUs: 66.7%, "other heterosexuals: 32.1%). Homosexual/bisexual men
      with casual partner(s) abroad used a condom more frequently than did others.
      CONCLUSION: 245 of 599 persons reported casual sex abroad during 1985-1989, and
      the different "risk groups" reported countries where most HIV infected persons
      belonged to their own "risk group". We have reason to believe that alcohol intake
      increased the likelihood of casual sexual activity and decreased the use of
      condom. Norwegian travellers need more information on the risks of casual sex
      abroad, the use of condoms and the combination of alcohol intake and casual sex.

PMID- 8300093
TI  - Surveillance of sexually transmitted diseases in France: recent trends and
      incidence.
AB  - OBJECTIVE: To present recent trends in sexually transmitted diseases (STDs) in
      France and to estimate the gonorrhoea incidence in 1990. METHODS: Trends were
      analysed from data of three surveillance systems: (1) STD clinics: number of
      diagnoses, (2) a sentinel voluntary General Practitioner (GP) network: mean
      number of acute male urethritis/week/GP, characteristics of the notified
      urethritis (age, presence of discharge, sexual orientation), (3) a sentinel
      voluntary laboratory network: mean number of gonorrhoea
      isolates/month/laboratory, characteristics of patients with positive isolates
      (sex, age, site of sampling) and of strains (PPNG and TRNG rates). To estimate
      the gonorrhoea incidence in France in 1990, results of a study held among a
      national sample of laboratories were used, combined with data from surveillance
      systems and specific studies. RESULTS: Decreasing trends in gonorrhoea in STD
      clinics and in the laboratory network as well as in acute male urethritis in the
      GP network have been observed since implementation of the networks in 1985. The
      rate of PPNG strains has regularly increased in the laboratory network to reach
      14% in 1991. Data suggest that the incidence in some acute non recurrent STDs
      could have increased among homo/bisexual men since 1988. Chlamydia trachomatis is
      now the most frequent diagnosis in STD clinics. Estimation of male gonorrhoea
      incidence rate in France in 1990 of 74/100,000 inhabitants (15-59 years) is
      consistent with figures observed in England and Wales, where the age distribution
      is very similar. On the other hand, the estimated female gonorrhoea incidence
      rate of 14/100,000, which concerns only microbiologically ascertained cases, is
      one third in France than that observed in England and Wales. CONCLUSION: The
      consistency of the decreasing trends in gonorrhoea and acute male urethritis
      observed from the different networks reduces the possibility of a bias due to any
      change in notification or in prescription. Trends in Chlamydia trachomatis will
      be better appraised in the near future with the recent implementation of new
      systems. The French STD surveillance appears quite satisfactory for male
      infections and has been able to show a marked decrease in the incidence of some
      STDs in the last years. Surveillance of female STDs is to be improved, in terms
      of monitored diagnoses and selected health care facilities. Differences between
      the female gonorrhoea incidence rate observed in England and Wales and the one
      computed for France could be attributed to differences in contact tracing
      policies between the two countries or to differences in sexual lifestyles.

PMID- 8300094
TI  - A comparison between cytology and histology to detect anal intraepithelial
      neoplasia.
AB  - INTRODUCTION: Anal intraepithelial neoplasia (AIN), which may be a precursor of
      anal carcinoma, has been identified on histology following minor anal surgical
      procedures, in particular the removal of perianal condylomata, in increasing
      numbers of homosexual and bisexual men. Anal cytology has recently been proposed
      as a useful method of identifying AIN lesions. OBJECTIVE: To compare anal
      cytology with histology as a method of detecting AIN. METHODS: 215 homosexual and
      bisexual men attending a central London sexually transmitted diseases clinic had
      an anal cytological smear performed under standard conditions. The perianal area
      and anal canal were then examined using a colposcope, and areas macroscopically
      suggestive of intraepithelial neoplasia were biopsied. RESULTS: 176 of the 215
      patients were biopsied of whom 76 had AIN on histology. 154 of the 215 patients
      had an adequate anal smear of whom 46 and 85 had cytological features of both HPV
      and AIN, or HPV alone respectively. Including features of HPV alone as an
      abnormal smear, anal cytology, when compared with anoscopy and histology as the
      gold standard for diagnosing AIN, resulted in a sensitivity of 87.5%, a
      specificity of 16.3%, a positive predictive value of 37.4% and a negative
      predictive value of 69.6%. Restricting abnormal smears to those with features of
      both HPV and AIN resulted in a sensitivity of 33.9%, a specificity of 72.5%, a
      positive predictive value of 41.3% and a negative predictive value of 65.7%.
      CONCLUSION: Anal cytology is a sensitive but nonspecific method of identifying
      patients with biopsy proven AIN if cytological features of HPV alone are included
      as abnormal smears. Specificity is improved by restricting abnormal smears to
      those with features of both HPV and AIN but this markedly lowers the sensitivity
      of the test. At present, anoscopy and histology are required in addition to anal
      cytology to differentiate between patients who simply have anal condylomata and
      those who also have AIN.

PMID- 8300095
TI  - Rectal spirochaetosis in homosexual men: the association with sexual practices,
      HIV infection and enteric flora.
AB  - OBJECTIVE: To determine the prevalence of rectal spirochaetosis in homosexual men
      attending a sexually transmissible diseases clinic and investigate the
      association between their presence and sexual practices, HIV infection and
      enteric flora. DESIGN: The study included 144 male homosexual subjects who each
      completed a questionnaire, underwent physical examination, proctoscopy and
      investigations for STD and HIV screening, rectal biopsies and collection of
      faecal samples. SETTING: The Sexual Health Centre, Sydney Hospital, Sydney,
      Australia. RESULTS: Spirochaetes were detected in 39% of the rectal biopsies,
      using histological criteria. Logistic regression analysis showed that rectal
      spirochaetosis was significantly associated with: oral-anal contact. (P < 0.05,
      OR 3.45, 95% CI 1.48-8.05); detection of 3-5 different non-pathogenic protozoa in
      faeces (P < 0.01, OR 11.68, 95% C.I. 2.33-58) and a positive HIV antibody test (P
      < 0.01) OR 4.48, 95% C.I. 1.28-15.72). CONCLUSIONS: These findings indicate that
      rectal spirochaetosis is relatively common in homosexual men. The association
      with non-pathogenic protozoa is most likely attributable to the common mode of
      transmission viz oral-anal contact. However it is difficult to determine whether
      the association with HIV infection is cause or effect because of the limitations
      in the study design. Further information is required to determine the clinical
      significance of infection with these organisms.

PMID- 8300096
TI  - Leukocyte esterase urine strips for the screening of men with urethritis--use in
      developing countries.
AB  - BACKGROUND AND OBJECTIVES: The leukocyte esterase (LE) strip is a useful tool for
      the screening of men with urethritis. In developing countries, where laboratory
      facilities are limited, and sexually transmitted diseases endemic, simple and
      inexpensive diagnostic tests which perform well, would be of great value.
      METHODS: Men presenting with urethritis to a referral clinic for sexually
      transmitted diseases in Nairobi, Kenya participated in this cohort analytical
      study. First-void urine was collected for LE dipstick testing as part of the
      diagnostic work-up. The results of the dipstick measurement were compared with
      the laboratory detection of Chlamydia trachomatis and Neisseria gonorrhoeae.
      RESULTS: Of 200 men with symptoms of urethritis, 33 (17%) had a pathogen detected
      from the urethra or the urine. Chlamydia was detected in urine by PCR in 22
      (11%), and gonorrhoea was cultured from the urethra in 11 (6%). Esterase activity
      (trace or greater) had a sensitivity of 76%, a specificity of 80%, a positive
      predictive value of 42% and a negative predictive value of 94% for the presence
      of chlamydia or gonorrhoea. CONCLUSIONS: The use of the LE dipstick for the
      screening of men with symptomatic urethritis can improve diagnostic accuracy and
      reduce the amount of empiric antimicrobial therapy. The low detection rate of
      chlamydia in these men with a clinical diagnosis of nongonococcal urethritis
      needs further study.

PMID- 8300097
TI  - Urinary tract infection in men with AIDS.
AB  - OBJECTIVE--To investigate whether bacteriuria and, specifically, symptomatic
      urinary tract infection (UTI) occur with increased frequency in men with HIV
      infection. METHODS--In this cross-sectional study we investigated three groups of
      men, aged from 18 to 50 years. Group A was composed of patients with a diagnosis
      of AIDS; Group B, of patients without HIV infection, and group C of patients with
      asymptomatic HIV infection. Patients with any known predisposing factor for UTI
      were excluded from the study. A clean-catch midstream urine sample was collected
      from each patient on the first day of hospital admission (groups A and B) or
      during a visit to the outpatient clinic (group C). Bacteriuria was diagnosed when
      > or = 100,000 colony forming units/ml, urine were grown. RESULTS--There were 415
      patients, 151 in group A, 170 in group B and 94 in group C. Bacteriuria was
      significantly more frequently in group A (20 cases, 13.3%) than in groups B (3
      cases, 1.8%, p = 0.00007) and C (3 cases, 3.2%, p = 0.009). Ten cases of
      bacteriuria in group A (6.6%) were symptomatic while no case of symptomatic UTI
      was seen in groups B (p = 0.0004) and C (p = 0.008). The frequency of UTI in
      homosexual men with AIDS (7 cases, 6.7%) was not significantly different from
      that observed in men with AIDS who denied homosexuality (3 cases, 6.5%). E coli
      was the predominant pathogen associated with UTI. Although adequate response to a
      two-week course of antibiotics was observed in most cases, an in-hospital
      mortality rate of 20% was found among AIDS patients with symptomatic UTI.
      CONCLUSIONS--In the present study, the frequency of bacteriuria and symptomatic
      UTI was found to be increased in men with AIDS. E coli was the predominant
      pathogen in these cases. These data suggest that symptomatic UTI may represent a
      relevant cause of morbidity for men with AIDS.

PMID- 8300098
TI  - Gonococcal infection in Edinburgh and Newcastle: serovar prevalence in relation
      to clinical features and sexual orientation.
AB  - AIMS: The variable distribution of gonococcal serovars in different areas is well
      recognised but the factors that are important determinants of serovar prevalence
      are less clear. The aim of this study was to identify relevant clinical variables
      by comparing serovar prevalence in two cities over the same time period. METHODS:
      A prospective analysis of serovar prevalence was made between January and
      December 1992 in Edinburgh and Newcastle with respect to age, sex, sexual
      orientation, antibiotic sensitivity and presence of symptoms. RESULTS: 224
      infective episodes of gonorrhoea were studied. The serovar distribution varied
      between the two cities with serovar 1B-1 being more common in Edinburgh (20/91
      cf. 4/133, p < 0.01) and serovar 1B-6 more common in Newcastle (26/133 cf. 2/91,
      p < 0.01). Serovar 1A-2 was associated with heterosexual infection (35/114 in
      heterosexuals cf. 0/85 in homosexuals, p < 0.01) and was more sensitive to
      penicillin than average (39/39 1A-2 strains highly penicillin sensitive cf.
      98/184 for all other strains, p < 0.01) whilst 1B-6 was mostly acquired through
      homosexual contact (22/26 cf. 63/142 for all other strains, p < 0.01) and tended
      to show reduced penicillin susceptibility (13/28 1B-6 strains less penicillin
      sensitive cf. 45/195 for all other strains, p < 0.01). Infection with serovar 1A
      2 was significantly less often symptomatic in heterosexuals than average (15/33
      asymptomatic 1A-2 infections cf. 17/59 for all other serovars, p = 0.015).
      Subgroup analysis of male heterosexual infections confirms an association between
      asymptomatic infection and serovar 1A-2 (2/14 asymptomatic 1A-2 infections cf.
      1/72 for all other serovars, p = 0.02). The distribution of infections over the
      year differed between the cities. CONCLUSIONS: A variety of factors including
      penicillin sensitivity and virulence may be important in determining the
      prevalence of gonococcal serovars within a given area.

PMID- 8300099
TI  - A prospective study of the psychological impact on patients with a first episode
      of genital herpes.
AB  - OBJECTIVES: To assess the psychological impact of first episode of genital
      herpes, and to determine whether this changes over time. SETTING AND SUBJECTS:
      The Departments of Genitourinary Medicine (GUM), and Dermatology, Middlesex
      Hospital London. The study group consisted of patients attending the department
      of GUM with a clinically proven first episode of genital herpes. Two control
      groups were recruited; firstly patients without herpes attending the GUM
      Department and secondly patients attending the Dermatology Department out
      patients with chronic dermatoses. METHODS: Patients and controls completed an 87
      item, self-administered psychological questionnaire at 3 monthly intervals for a
      year. The questionnaire consisted of the General Health Questionnaire (GHQ); the
      Hospital Anxiety and Depression Questionnaire (HADQ); Illness Attitude Scales and
      Illness Concern. Patients were also asked questions about their sexual behaviour.
      RESULTS: Ninety one patients (68 women, 23 men) with genital herpes, 61 GUM
      controls (42 women, 19 men) and 56 dermatology controls (36 women, 20 men)
      participated. There were no statistically significant demographic differences
      between patients and controls. At first visit the proportion of patients
      classified as "cases" by the GHQ (GHQ cases) were similar for primary herpes
      patients 62% (56/91) and Dermatology controls 52% (29/56) while a significantly
      smaller proportion of GUM controls 34% (21/61) were classified as GHQ cases. The
      primary herpes group were significantly more concerned about their illness than
      either the GUM controls or the Dermatology controls (p < 0.002). The proportion
      of primary herpes patients classified as "cases" by the GHQ reduced significantly
      over the initial three month period with 67% of patients classified as "cases" at
      their first visit becoming "noncases" after three months (p < 0.0001). Also 50%
      of those classified as "cases" at first visit by the HADQ become "noncases" after
      the initial three months (p = 0.007). The illness concern scores also decreased
      significantly from visit one to visit two (means 14.7 vs. 12.3; p < 0.0001).
      CONCLUSION: The diagnosis of a first episode of genital herpes has a profound
      emotional effect on patients. If they do not have recurrent episodes, their
      emotional state improves. For those who do have recurrences, the level of anxiety
      and concern remains as high as at the time of their first diagnosis. Clinicians
      must be sensitive to the emotional impact such a diagnosis may bring.

PMID- 8300100
TI  - Bartholin's abscess complicating food poisoning with Salmonella panama: a case
      report.
AB  - A patient is presented who developed an acute Bartholin's abscess four weeks
      after an attack of Salmonella panama enteritis. Aspirate from the abscess also
      grew Salmonella panama, indistinguishable from the gut isolate in serotype and
      antigenic structure (1 9, 12: 1, v: 1,5). Some aspects of the microbiology of
      Bartholin's abscess and its clinical management are discussed.

PMID- 8300101
TI  - Umbilical warts: a new entity?
AB  - Two cases of umbilical warts are described. The occurrence of these lesions was
      not previously known. In both cases there was a history of long-standing genital
      warts.

PMID- 8300102
TI  - Recurrent pseudomembranous colitis due to Clostridium difficile in AIDS.

PMID- 8300103
TI  - Sexually transmitted diseases in Canada, 1800-1992.
AB  - The history of sexually transmitted diseases in Canada from 1800 to the present
      reflects the changing views and values of citizens, medical experts, politicians
      and bureaucrats. During the colonial period, the military devoted attention to
      the problem but strict moral codes and social conventions prevented public
      discussion. Although middle class reformers began to pressure the federal
      government for funding and direction after 1900, World War I was the catalyst for
      involvement. Health education through a voluntary group and federal-provincial
      cost-shared funding for treatment facilities across Canada were introduced to
      control STDs. Public perception of STD patients as marginalised or deviant
      limited the impact of these efforts. Social changes during the 1960s, new STDs
      appearing in the 1970s and the AIDS epidemic of the 1980s have redirected the STD
      campaign to focus on high risk groups and prevention rather than the moralistic
      curative efforts of the past.

PMID- 8300104
TI  - AIDS, memory and the history of medicine: musings on the Canadian response.
AB  - This paper presents the history of AIDS in Canada with special attention to
      epidemiology, public policy, and social commentary. The interest in medical
      history sparked by the epidemic is studied in relation to its impact on public
      health measures. Conversely, the impact of the disease itself on the history of
      medicine is examined. AIDS seems to have had a greater impact on history in
      Canada than history has had on the Canadian response to AIDS.

PMID- 8300105
TI  - Genital ulcer disease: accuracy of clinical diagnosis and strategies to improve
      control in Durban, South Africa.
AB  - OBJECTIVE: To investigate the accuracy of clinical diagnosis in genital ulcer
      disease (GUD); to devise management strategies for improving the control of GUD
      and thereby limit the spread of HIV-1 infection. DESIGN: Clinical and
      microbiological assessment of GUD in men and women. The index of suspicion,
      diagnostic accuracy, diagnostic efficiency and positive and negative predictive
      values of a clinical diagnosis were investigated. SETTING: City Health Sexually
      Transmitted Diseases Clinic, King Edward VIII Hospital, Durban, South Africa.
      PARTICIPANTS: 100 men and 100 women with genital ulcers. RESULTS: The accuracy of
      a clinical diagnosis was, in men: lymphogranuloma venereum (LGV) 66%, donovanosis
      63%, chancroid 42%, genital herpes 39%, primary syphilis 32%, mixed infections
      8%, and in women; secondary syphilis 94%, donovanosis 83%, genital herpes 60%,
      primary syphilis 58%, chancroid 57%, LGV 40%, mixed infections 14%. Overall,
      diagnostic efficiency was greater in women than in men. When compared with other
      causes of GUD, donovanosis ulcers bled to the touch and were larger and not
      usually associated with inguinal lymphadenopathy. In women, extensive vulval
      condylomata lata were readily differentiated from all other causes of GUD.
      CONCLUSION: A clinical diagnosis in genital ulceration was less accurate in men
      than in women. The diagnostic accuracies for donovanosis and secondary syphilis
      were relatively high but for most other conditions were low. Differences between
      clinical and laboratory diagnostic accuracies may reflect similarities between
      the clinical appearances of the various causes of GUD, the presence of mixed
      infections, atypical ulceration due to longstanding disease, and insensitive
      laboratory tests. In this community all large ulcers should be treated
      empirically for syphilis and donovanosis. Uncircumcised men with GUD are an
      important HIV core or "superspreader" group locally, and prevention strategies
      should include counselling and health education in the light of the inaccuracy of
      clinical diagnosis found in this study. The development of rapid accurate tests
      for GUD is urgently required.

PMID- 8300106
TI  - Prevalence of antibodies to HPV16-E7-protein does not differ between AIDS
      patients with and without Kaposi's sarcoma.

PMID- 8300107
TI  - Screening for genital Chlamydia trachomatis infection in female patients.

PMID- 8300108
TI  - HIV seroprevalence among eunuchs.

PMID- 8300109
TI  - STD and inflammatory cervical cytology.

PMID- 8300110
TI  - Mycoplasmas and non-gonococcal urethritis.

PMID- 8300111
TI  - Neisseria gonorrhoeae isolates at St Mary's Hospital, London 1980-91.

PMID- 8300112
TI  - Benefit related assessment of treatment need among institutionalised elderly
      people.
AB  - It has been assumed that improved oral health leads to a better quality of life
      for elderly people. It is, however, difficult to assess the benefit of oral
      health care, especially dental treatment in terms of life quality. The normative
      assessment, based solely on clinical diagnosis, often leads to an overestimation
      of the true need for treatment, especially among the 'frail elderly', some of
      whom do not want treatment, either because there is no perceived need or
      expressed demand. Others are very ill, and some in such a poor mental condition
      that they can not express any demand for treatment, and would probably not
      benefit from treatment e.g. new dentures. The realistic treatment need is an
      attempt to assess the true need for treatment in relation to the benefit
      provided. It is a combination of the normative need, the self-perceived need, and
      the expressed demand for treatment, and takes into account the mental and
      physical state of the individual, as well as ethical considerations.

PMID- 8300113
TI  - Changes in human jaw muscles with age and dental state.
AB  - The effects of ageing and dental state on the cross-sectional area and density of
      two jaw muscles, the masseter and medial pterygoid, were investigated using
      computed tomography. The study involved 84 male and 70 female subjects between
      the ages of 20 and 90 years. The cross-sectional area of both muscles showed a
      significant reduction with age; values for female subjects being found in the
      lower range of the distribution. When consideration was given to the presence or
      absence of a natural dentition, the cross-sectional area of both muscles in
      edentulous subjects showed a greater decrease throughout the age range studied.
      There was a significant decrease in the density of the muscles with increasing
      age. Previously, this has been interpreted to indicate a progressive increase in
      fat and fibrous tissue. Subject gender and the absence of teeth appeared to have
      little effect on this parameter. Changes in the cross-sectional area and density
      of these muscles would appear to be consistent with a general age related change
      of muscle tissue in the body as a whole and may specifically indicate a reduction
      in the masticatory forces which can be or are being utilised by ageing patients,
      many of whom have no remaining natural dentition.

PMID- 8300114
TI  - Experimental studies of adaptation to complete dentures related to ageing.
AB  - The assessment of a patient's capability to adapt to new dentures is still a
      challenge in the prosthetic treatment of geriatric patients. The aim of this
      study was to assess the relationship of age to manual motor ability as well as
      the mental concentration capacity in comparison to the oral motor ability and the
      capability to adapt to new dentures. Sixty complete denture wearers volunteered
      for the experiment. The results indicate, that the manual motor ability and the
      mental concentration capacity deteriorate with age, whereas the relationship of
      age to adaptation to new dentures and oral motor ability is less obvious. This
      may be due to the patient's denture experience.

PMID- 8300115
TI  - Implant therapy alternatives for geriatric edentulous patients.
AB  - The predicament of being both elderly and edentulous undermines life quality for
      both patient and dentist. The former suffer because of morphological and
      functional compromises, the latter because of a dearth of safe and predictably
      successful clinical techniques. The introduction of the osseointegration
      technique suggested great promise for profoundly changing this predicament, but
      the specific merits of this approach have been mainly extrapolated ones. The
      purpose of this study was to examine the clinical success of treatment with
      osseointegration for patients who were 65 or older at the time of implant
      insertion. A second group of patients, who became 65 during the course of the
      study was also studied and the results recorded separately. Data regarding the
      longevity of implants and prosthodontic restorations and the numbers and types of
      problems encountered were recorded. The evidence suggests that the biological
      anchorage of tooth root analogues in elderly jaws is predictably successful and
      enhances the quality of life for geriatric patients who are edentulous.

PMID- 8300116
TI  - Demography and dental needs, an international perspective.
AB  - The population of the world is changing and the science dealing with the study of
      these changes in human populations, in terms of disease, health and mortality has
      been called demography. It can be understood to include the evaluation of the
      size, density, and distribution of populations including the influence of a
      variety of factors such as age and economics. This paper will review the
      distribution of the world's population with regard to age and utilization of
      dental care with particular emphasis on the older cohorts.

PMID- 8300117
TI  - Patient age and long term survival of fixed prosthodontics.
AB  - The possible relationship between patient age and the long term survival of fixed
      prostheses was studied in a randomised group of persons, who had received
      restorative treatment by general practitioners 15 years prior to this study.
      These fixed partial dentures had a mean extension of 6.9 units and a mean
      pontic/abutment ratio of 0.47. The group studied consisted of 77 persons who
      agreed to participate from an original group of 150 persons. Of the original
      group 20 had died, 17 were not traceable or unable to participate for medical
      reasons, and 36 declined to participate. The outcome of the treatment was
      compared between the following age subgroups (age as at the time of the original
      treatment) by division of the data at 37, 60 and 65 years. In these subgroups
      between 20 and 50 per cent of the prostheses had been lost or partially lost
      during the fifteen year period. Most of the failures and unacceptable quality
      ratings were found to be caused by fractures, loss of retention and/or dental
      caries. However, no systematic differences were found between any of the age
      subgroups studied.

PMID- 8300118
TI  - Oral function in dentate elderly with reduced dentitions.
AB  - This study covers the characteristics of reduced dentitions in a population of
      elderly people. The sample consisted of 329 independently living individuals
      between 55 and 75 years of age. They all had one or more natural teeth and were
      all interviewed and investigated clinically. The findings showed that 13% of the
      subjects had a natural dentition with at least the first molars; 4-7 natural
      occlusal units (defined as 'pairs of opposing teeth that support the occlusion')
      occurred in 37% of the subjects; 1-4 natural occlusal units in 41% and 0 units in
      9% (only anterior contacts). A removable partial denture was worn by 39% of the
      subjects; most of them were acrylic based dentures (61%). The percentages of
      restored teeth per subject were high. The need for further restorations, however,
      was low. Periodontal problems were uncommon; 25% of the subjects had one pocket
      above 5 mm; 8% had severe problems. Poor oral hygiene was present in a quarter of
      the cases. Most of the subjects (70%) had no pain or noises in the
      temporomandibular joint. Only 10% of subjects had more than one sign of
      craniomandibular dysfunction. Most of the subjects (85%) visit their dentist
      regularly and 65% had their last tooth extraction more than three years ago. A
      majority mentioned that they have never had problems with their dentition in the
      past; 50% had had no real toothache for the last five years. However, problems
      with food-packing were often mentioned. It can be concluded that, although the
      dentitions of the elderly in this population are often reduced, their dentitions
      are in general in good condition and few give TMJ problems.

PMID- 8300119
TI  - Medical and dental status of a culture in transition, the case of the Inuit
      elderly of Canada.
AB  - The medical and dental status, and drug utilisation patterns of Canadian Inuit
      elders (60+ years) were evaluated. Inuit elders averaged 6.3 medical conditions
      per person, primarily nervous systems-sense organ deficits, respiratory problems
      and systemic infections. The mean number of drugs being used was 2.5 per person,
      primarily analgesics, bronchodilators and antibiotics. Poorly fitting dentures,
      and high levels of tooth decay, periodontal disease, soft tissue and TMJ
      anomalies were documented. Compared to older southern Canadians, the medical and
      dental findings for these Inuit elders were different. Drug utilisation rates
      were consistent with older southern Canadians, but different drugs were taken.

PMID- 8300120
TI  - Advances and outlooks for immunotherapy of cancer.

PMID- 8300121
TI  - Idiotypic network and tumor therapy. Proceedings of the First International
      Meeting of Immunological Approaches to Tumor Therapy by Antibodies and Tumor Cell
      Vaccines. Bonn, February 6, 1993.

PMID- 8300122
TI  - Ovarian carcinoma therapy with monoclonal antibodies.

PMID- 8300123
TI  - Anti-idiotypes in melanoma.

PMID- 8300124
TI  - Anti-idiotype vaccine in colorectal cancer patients.

PMID- 8300125
TI  - Antitumor antibodies for immunotherapy of ovarian carcinomas.

PMID- 8300126
TI  - A non-lymphoma idiotype is indicative and predictive for B cell malignancies in
      AIDS.
AB  - The 1F7 idiotype previously defined (J Immunol 147:933;1991 and Eur J Immunol
      22:1749;1992) is expressed on antibodies reactive to different proteins of HIV
      (gp41, p24, gp120). Since serum levels of 1F7 (IgM or IgG) are significantly
      higher in patients with HIV lymphoma as opposed to HIV-infected individuals,
      normal controls and non-HIV lymphoma patients, we hypothesized the B-cell
      neoplasms were the source of the idiotype. However, immunohistochemistry on
      cryostat sections revealed no 1F7 idiotype signal on neoplastic B-cells nor tumor
      infiltrative T-cells (n = 8). Interestingly, reactive lymphocytosis adjacent to
      tumor masses and reactive follicular hyperplastic controls (n = 5) exhibited
      significant 1F7 reactivity. The reactivity appeared in paracortical and
      perifollicular lymphoid regions, predominantly regions of B, T and antigen
      presenting cells in lymph nodes or tonsils. A survey of electrophoretically
      defined paraproteins with anti-HIV specificities derived from HIV-infected
      patients showed no Western blot reactivity with the 1F7 anti-idiotypic antibody.
      Therefore, the idiotype does not appear to be a direct product of B-cell
      neoplasia or abnormal B-cell proliferation, but is produced by B cell clones
      responding to HIV infection. This high level of serum 1F7 reactivity could be an
      important clue in the pathogenesis of HIV lymphomas and confers a highly
      predictive serological test for HIV lymphoma.

PMID- 8300127
TI  - Antibody-targeted photodynamic therapy.

PMID- 8300128
TI  - Tumor cell vaccination and IL-2 therapy.

PMID- 8300129
TI  - Influence on antigen exposition of tumor cells by membrane active substances and
      viral infections.

PMID- 8300130
TI  - Autologous tumor-cell vaccination and lymphokine-activated tumor-infiltrating
      lymphocytes (LAK-TIL).

PMID- 8300131
TI  - Influence of MAb (F(Ab)2 OC 125 on the survival rate of ovarian carcinoma
      patients.

PMID- 8300132
TI  - Influence of human anti-murine antibodies on in vitro assays in ovarian cancer
      patients.

PMID- 8300133
TI  - Idiotypic cascades after MAb OC125 application.

PMID- 8300134
TI  - Clinical course of ovarian cancer patients under repeated stimulation of HAMA
      using MAb OC125 and B43.13.

PMID- 8300135
TI  - Production and characterization of specific asialoglycoprotein receptor
      antibodies.
AB  - Monoclonal antibodies (MoAbs) were produced by immunizing BALB/c mice with
      asialoglycoprotein receptor (AGPR) purified from human liver. The purity of AGPR
      was confirmed by SDS-polyacrylamide gel electrophoresis and by amino acid
      sequence. An enzyme-linked immunoassay revealed 24 monoclonal antibodies which
      reacted with human AGPR. By Western blot analysis, all antibodies recognized the
      46 kDa human AGPR under the non-reduced conditions and four MoAbs recognized
      reduced protein. Two MoAbs reacted with AGPR derived from rat, rabbit and mouse
      liver under both non-reduced and reduced conditions, suggesting that we could
      obtain antibodies which reacted with AGPR epitopes shared by different species.
      In immunohistochemical studies, 30201-MoAb reacted with human liver tissue but
      not with other tissues. This antibody immunoprecipitated two major bands of 46
      kDa and 39 kDa from [35S]-methionine metabolically labeled human hepatoma HepG2
      cells. The determinant recognized by 30201-MoAb is a common epitope of AGPR which
      is present in different species and in both the precursor and maturation forms of
      the receptor.

PMID- 8300136
TI  - Preparation and biological properties of monoclonal antibodies against human
      erythropoietin.
AB  - Several monoclonal antibodies (Mabs) against human erythropoietin (H-EPO) were
      obtained by fusion of myeloma cells with splenocytes from mice immunized with
      purified recombinant H-EPO. Three Mabs (D7, E14 and E73) were selected by
      radioimmunoprecipitation on the basis of their high affinity against H-EPO. Their
      dissociation constants were 0.3 nM for E14 and D7, and 17 nM for E73. The
      immunochemical properties of these Mabs were analyzed in respect to their
      capacity to react, to purify, and to inhibit the biological activities of H-EPO.
      a) detection by Western blotting techniques: among the 3 Mabs only D7 was
      effective by this technique. b) purification: the best results were observed with
      E14, an approximately 200-fold purification of H-EPO from culture supernatants
      was obtained in a single immunopurification step. c) inhibition of the biological
      activity: the specific binding of 125I-labelled H-EPO to its cellular receptor
      was inhibited by E14 and E73 but not by D7. These three Mabs exhibited similar
      effects as far as the inhibition of the proliferation of H-EPO dependent cells
      (measured by 3H-thymidine incorporation) was concerned.

PMID- 8300137
TI  - A monoclonal anti-human IL-6 receptor antibody inhibits the proliferation of
      human myeloma cells.
AB  - A monoclonal antibody (UV4) against the human IL-6 receptor (hIL-6R) was
      generated by immunizing BALB/c mice with both a human myeloma cell line (U266)
      and a murine cell line (M12.4/R) transfected with the hIL-6R cDNA. Flow
      cytometric analysis demonstrated that UV 4 stains the hIL-6R+ cell lines U266 and
      U937, but not the hIL-6R- cell lines Daudi and K562. Competitive inhibition
      assays demonstrated that preincubation of U266 cells with UV4 inhibited the
      binding of a phycoerythrin (PE)-IL-6 conjugate to the hIL-6R and also inhibited
      the proliferative activity of IL-6 on the IL-6-dependent human myeloma cell lines
      ILKM2 and ILKM3. In contrast, UV4 did not interfere with the proliferation of the
      hIL-6R- Burkitt's lymphoma cell line, Daudi. Direct sandwich radioimmunoassays
      further confirmed that the UV4 bound to the same molecule as the goat anti-hIL-6R
      antibody. These results suggest that both UV4 and human IL-6 bind to the same or
      adjacent epitopes on the hIL-6R. This monoclonal antibody should facilitate
      studies of the structure-function relationship of IL-6R and may be useful for the
      treatment of IL-6-dependent diseases such as multiple myeloma.

PMID- 8300139
TI  - Carotid body paraganglioma with coexistent pheochromocytoma in childhood.
AB  - A male child aged six years presented with a swelling in neck and hypertension.
      He was diagnosed to have and operated for Carotid body paraganglioma with
      Coexistent pheochromocytoma. Hypertension persisted even after excision of both
      the tumours which could be controlled with anti-hypertensive agents. The case is
      discussed with review of literature.

PMID- 8300138
TI  - Familial occurrence of cancer in Basel city.
AB  - The Basel Familial Cancer Study was established in 1982. Data collection and
      statistical analysis suggest that genetic mechanisms play an important role in
      most cancer types. This is illustrated in breast and colorectal cancer patients
      whose first degree relatives were studied. The establishment of a familial cancer
      registry is most helpful for cancer risk determinations, surveillance and
      management programmes, identification of new cancer prone genotypes and
      etiological family studies. The family history should be included into future
      cancer control activities.

PMID- 8300140
TI  - Late radiation induced laryngeal oedema in the treatment of vocal cord cancer:
      analysis using the linear quadratic model.
AB  - The incidence of late complications for different size of dose per fraction is
      analysed in 208 cases with squamous cell carcinoma of the vocal cord. The series
      comprised 156 cases with T1 and 52 cases with T2 lesions. Radical radiotherapy
      was given with three different regimens having dose per fraction as 3.33, 2.5 and
      2.25 Gy. There were 46 cases with persisting radiation induced laryngeal oedema.
      Using two different statistical methods, an alpha/beta value of 2.38 Gy of linear
      quadratic model was estimated for late complications of vocal cord. The analysis
      indicate the increased incidence of late complications with size of dose per
      fraction. Relevance of linear quadratic model for the prediction of late
      complication is demonstrated in the present study.

PMID- 8300141
TI  - Primary radiation therapy in the management of glomus tumours.
AB  - The records of five patients who received local irradiation for incompletely
      excised or inoperable glomus tumour were retrospectively reviewed. Age ranged
      from 25 to 46 years. There were two female and three male patients. Two patients
      who were solely treated by radiation therapy remain clinically disease free at 30
      and 42 months respectively. Of the remaining three patients, where radiotherapy
      was delivered post operatively, one achieved complete remission and is well and
      alive at 60 months, whereas the other two patients were lost to follow up at 22
      and 26 months respectively after showing an early clinical improvement. We
      advocate the efficiency of radiation therapy as primary treatment in the
      management of primary glomus tumour.

PMID- 8300142
TI  - Serum sialic acid--an important cancer marker.
AB  - Total serum sialic acid (TSA), Lipid associated sialic acid (LASA), Total protein
      (TP) and TSA/TP factor (as cancer markers) have been estimated in 78 patients of
      cancer stomach, breast, colorectal region and gall bladder, before and after
      treatment and of varying degrees of metastasis and compared to 30 healthy
      controls. A significant rise in TSA and TSA/TP factor and a decrease in serum
      total protein levels was found in all cases of cancer. This increase was directly
      proportional to the degree of metastasis i.e. tumour burden. Serum TP levels were
      found decreased in all patients. Rise in LASA levels was not significant. Raised
      TSA/TP levels became lower to certain extent after effective therapy. Hence it
      can be inferred that although TSA and TSA/TP are not specific they are however,
      sensitive markers regarding detection of malignancy and useful in monitoring
      cancer progression and/or recurrent while evaluating the efficacy of various
      cancer therapies.

PMID- 8300143
TI  - Craniofacial excision for recurrent osteogenic sarcoma of maxilla.
AB  - Two cases of recurrent osteogenic sarcoma of the antro-ethmoidal complex treated
      at our hospital by a craniofacial resection are presented. The imperative need to
      treat osteogenic sarcomas of the maxilla primarily by a radical approach such as
      a craniofacial resection is emphasized.

PMID- 8300144
TI  - Multicentric giant cell tumour of bone--a report of two cases.
AB  - Two cases of metachronous multicentric giant cell tumour of bone are reported.
      One patient had tumours in the tibia and the femur, the second tumour appearing
      five years after the first. The other patient developed tumours in the tibia and
      the radius, the second tumour appearing two years and nine months after the
      first. The metachronous tumours, in both cases, were clinically and
      radiologically more aggressive than the initial tumours. Treatment with curettage
      and bone grafting proved to be ineffective for these tumours and en-bloc excision
      was required for cure.

PMID- 8300145
TI  - Double malignancy in a benign cystic teratoma of the ovary (a case report).
AB  - A case of malignant change in a benign cystic tertoma of the ovary has been
      reported where there was double malignancy. Leiomyosarcoma was associated with
      squamous cell carcinoma (In situ). The patient remained well for one year after
      ovariotomy.

PMID- 8300146
TI  - Acute lymphatic leukemia and pregnancy.
AB  - Acute lymphatic leukemia (ALL) was diagnosed in a pregnant patient after she
      presented with features of superior vena cava obstruction. Patient received
      chemotherapy during the course of pregnancy. A premature but normal female child
      was born. A brief review of literature with respect to the toxicity of cytostatic
      drugs to fetus and mother is made. Although adults with ALL frequently achieve a
      complete remission, the decision about conception and pregnancy need to be
      individualized because of unpredictable course.

PMID- 8300147
TI  - Unusual bone metastasis as the initial symptom of gastric cancer--a report of
      four cases.
AB  - Four cases of gastric cancer presenting with bone pain due to metastasis as the
      initial symptom are reported. Investigations revealed solitary osteolytic
      metastasis in the mandible in one, and left scapula in one patient. Third patient
      had multiple osteosclerotic metastasis with elevation of acid phosphatase and
      another had multiple discrete osteolytic metastasis simulating multiple myeloma.
      All the primary gastric cancers were poorly differentiated adenocarcinoma and
      three were of Borrman type III on gross appearance. One patient had sparing of
      the liver inspite of extensive metastasis. Chemotherapy was in effective in two
      patients and the prognosis was uniformly poor.

PMID- 8300148
TI  - A novel target cell antigen involved in the NK-like lytic activity of antigen
      specific cytotoxic T lymphocytes.
AB  - Monoclonal antibodies (mAbs) have been derived which identify a target cell
      antigen involved in human natural killer (NK) cell lysis. The effects of the mAbs
      on the NK-like cytotoxic activity exhibited by different populations of human
      cytolytic T cells were examined. The anti-target cell mAbs 1E7 and 18C2 inhibited
      the lysis of K562 target cells by endogenous NK cells, antigen-specific cytotoxic
      T lymphocytes (CTL) with NK-like activity, and non-major histocompatibility
      complex (MHC)-restricted T cells. Cytolysis of K562 target cells was not affected
      by treatment of the target cells with the anti-class I HLA mAb W6/32. Further,
      the anti-target cell mAbs had no effect on antigen-specific lysis by the CTL. The
      mAb W6/32, however, inhibited the antigen-specific killing. Experiments at the
      single-cell level revealed that the anti-target cell mAbs inhibited the formation
      of conjugates between the effector cells and K562 tumor cells but had no effect
      on CTL binding to the antigen-specific target cells. Thus, antigen-specific CTL
      exhibiting NK-like lytic function appeared to recognize a novel target cell
      antigen that is distinct from typical MHC antigens and is identical to the target
      cell antigen recognized by true NK cells.

PMID- 8300149
TI  - Mouse thymic dendritic cell subpopulations.
AB  - Mouse thymic dendritic cells (DC) have been isolated after collagenase digestion,
      selection of the low-density cell fraction, then depletion of T-lineage cells and
      other non-DC by treatment with specific monoclonal antibodies (mAb) and removal
      with anti-Ig-coated magnetic beads. The resulting DC preparation represented 0.1
      0.2% of total thymic cells and contained 70-80% DC. Flow cytometry analysis of
      MHC class II (MHC II) expression by DC showed that 40% of DC expressed
      intermediate levels of MHC II, and 60% expressed high levels of this marker.
      Moreover, immunofluorescent 2-colour staining allowed the characterization of two
      clearly distinguishable DC subpopulations: MHC IIinter DC were CD45hi, CD44hi,
      HSAhi, whereas MHC IIhi DC were CD45lo, CD44lo, HSAlo. These results are
      discussed with regard to the functional significance of MHC IIinter and MHC IIhi
      DC subpopulations in the mouse thymus.

PMID- 8300150
TI  - Human recombinant GM-CSF selectively primes receptor mediated respiratory burst
      of neutrophils in vitro.
AB  - The influence of human recombinant granulocyte-macrophage colony-stimulating
      factor (rH GM-CSF) on respiratory burst response of isolated human neutrophils
      was examined. Preincubation of cells with rH GM-CSF significantly increased the
      respiratory burst in response to formyl-methionyl-leucyl-phenylalanine (FMLP),
      measured by luminol-dependent chemiluminescence (CL) assay. This priming effect
      of rH GM-CSF was independent of extracellular Ca2+ and Mg2+. On the other hand,
      the pretreatment of cells with rH GM-CSF could not enhance the neutrophil CL
      responses to unopsonized, serum complement-opsonized or immunoglobulin G (IgG)
      opsonized zymosan particles. rH GM-CSF directly induced a weak CL signal in
      neutrophils. This signal, however, was abolished when extracellular Ca2+ and Mg2+
      were removed. Exposure to rH GM-CSF caused a divalent cation-dependent up
      regulation of complement receptors (CR1 and CR3) on neutrophil cell surface,
      while the expression of IgG Fc-receptors (FcRII and FcRIII) was not markedly
      changed by rH GM-CSF. The results indicate that rH GM-CSF primes FMLP-induced CL
      but not zymosan particle-induced respiratory burst in human neutrophils. It is
      hypothesized that the reason for the different sensitivity of FMLP-receptors and
      receptors to zymosan particles to rH GM-CSF priming may lie in differences in the
      signal-transduction pathways of these receptor types.

PMID- 8300151
TI  - Migration patterns of lymphocytes following syngeneic heterotopic small bowel
      transplantation in rodents.
AB  - Adult rats received syngeneic accessory small bowel grafts with venous drainage
      to either the portal vein (hetero-portal) or the inferior vena cava (hetero
      systemic). Lymphoid cell recovery in different lymphoid organs (spleen, pooled
      peripheral lymph nodes, mesenteric nodes, Peyer's Patches) was evaluated at
      varying times (days 0-300) post-grafting. While minimal changes were observed for
      cell recovery in other organ tissues, lymphocyte recovery in Peyer's Patches of
      both host and graft small intestine of hetero-systemic animals was decreased from
      10- to 100-fold with respect to hetero-portal recipients or non-operated
      controls. These changes were seen throughout the time course of the study. In
      additional experiments, lymphoid cells from different organs/donors were labelled
      in vitro with 111In and injected intravenously into normal/transplanted
      recipients. Recovery of 111In in various organs was assessed at 1 and 6 h
      postinjection. The major change seen was in the decreased ability of mononuclear
      cells derived from Peyer's Patches to migrate to small intestinal tissue (host
      and graft) in hetero-systemic recipients. In addition, Peyer's Patch cells from
      these animals 'homed' poorly to small intestine in non-operated animals by
      comparison with cells from normal rats (or hetero-portal donors).

PMID- 8300152
TI  - Evidence for interleukin-1 beta being a necessary but not sufficient co
      stimulatory signal in monocyte-dependent anti-CD3-mediated T-cell triggering.
AB  - T-cell activation by CD3-specific antibodies is either monocyte independent or
      monocyte mediated, depending on the fine specificity and mode of presentation of
      anti-CD3. Monocyte-independent activation occurs when T cells encounter surface
      bound antibody at high density, thereby mediating interleukin-2 (IL-2)
      production. Monocyte-dependent activation occurs upon bipolar binding of anti-CD3
      to CD3 of T cells and to Fc receptors of accessory cells (monocytes). We
      addressed the role of interleukin-1 (IL-1) as a co-stimulatory signal in monocyte
      dependent anti-CD3-mediated T-cell proliferation by using specific and anti-IL-1
      subtype antibodies and IL-1 receptor antagonist (IL-1ra). IL-1ra blocked
      proliferation of mononuclear cells (MNC) induced by fluid-phase anti-CD3, and
      proliferation of nylon wool-purified cells (NWPC; < 1% monocytes) exposed to low
      density, but not high-density, anti-CD3 coats. Stimulation of MNC by fluid-phase
      anti-CD3 and of NWPC by low-density anti-CD3 coats could both be blocked by anti
      IL-1 beta, but not by anti-IL-1 alpha, although the latter efficiently blocked IL
      1 alpha-mediated thymocyte co-stimulation. Neither the addition of IL-1 beta
      (given alone or combined with IL-6 and/or IL-1 alpha) nor anti-CD3-independent,
      LPS-induced cytokine induction in monocytes provided the co-stimulatory signal(s)
      for anti-CD3-triggered T cells in the absence of bipolar anti-CD3
      binding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300153
TI  - An immuno-dominant sequential epitope recognized by mouse anti-recombinant bovine
      growth hormone antisera.
AB  - The sequential epitopes on bovine growth hormone (bGH) recognised by five
      polyclonal mouse antisera have been identified by scanning with multiple pin
      bound peptides. Four main epitopes were identified at residues 29-40, 101-110,
      139-152 and 181-191. Of these, only epitope 139-152 is recognised by all five
      mouse antisera indicating that, for the mouse, this may represent an immuno
      dominant region of the bGH molecule.

PMID- 8300154
TI  - Production and characterization of monoclonal antibodies to embryo-associated
      immunosuppressor factor (EASF) produced by human pre-implantation embryo.
AB  - Balb/c mice were immunized with pre-implantation embryo-associated
      immunosuppressor factor (EASF) (purified from embryo growth media of in vitro
      fertilized human ova). Hybridoma clones were produced by fusing their spleen
      cells with NS1 and P3X653 myeloma cell lines. The presence of specific anti-EASF
      monoclonal antibodies (mAb) in the hybridoma culture supernatants were tested by
      enzyme-linked immunosorbent assay. A total of 15 hybridoma clones were selected,
      and their products were purified and characterized. Each mAb bound specifically
      to its antigen in a dose-dependent manner. The affinity-purified EASF from embryo
      growth media demonstrated immunosuppressive activity on Concanavalin A-induced
      lymphocytes and the presence of 14 kDa, 24 kDa and 37 kDa factors. No such
      activity or similar molecules were identified when control growth media were
      analyzed. This clearly demonstrates that these mAb are indeed EASF-specific and
      are able to recognize biologically active immunosuppressive components in embryo
      growth media. These mAbs are presently being tested for the development of EASF
      specific assay system.

PMID- 8300155
TI  - MHC class I up-regulation protects some but not all targets against LAK-mediated
      lysis: possible implications for the existence of LAK cell subpopulations using
      different recognition strategies.
AB  - The effect of gamma-interferon (gamma-IFN) was examined on the lymphokine
      activated killer (LAK) cell susceptibility and the levels of major
      histocompatibility complex (MHC) class I antigen expression on YAC, P815 and EL4
      cells. IFN induced a marked increase in the MHC class I antigen expression on all
      target cells, a concomitant decrease in LAK sensitivity was observed for YAC and
      P815 cells but not for EL4 cells. In competition experiments, lysis of YAC cells
      by LAK cells was inhibited by control or IFN-treated YAC and P815 cells, but not
      by control or IFN-treated EL4 cells. Moreover, lysis of EL4 cells was not
      inhibited by control or IFN-treated YAC cells. Our results suggest that the
      effectors killing EL4 are distinct from those killing YAC and/or P815 and that
      the former are not influenced by the levels of MHC class I antigens on target
      cells.

PMID- 8300156
TI  - Localisation of human peripheral blood leukocytes after transfer to C.B-17
      scid/scid mice.
AB  - Severe combined immunodeficient (scid) mice of the inbred strain C.B-17 lack
      functional T and B cells and, because of this, they tolerate xenografts. We
      reconstituted scid mice with human peripheral blood leukocytes (PBL) by i.p.
      injection. In order to determine the human PBL in lymphoid organs of these
      reconstituted scid mice, we labelled the human PBL prior to transfer with the
      fluorescent dye PKH 26-GL. With this experimental approach it was possible to
      detect the human cells in lymphoid organs and peritoneal exudate of the
      reconstituted scid mice by cytofluorimetrical and histological methods. This
      method is thus helpful for the determination of xenografts transplanted upon scid
      mice as well as in other experimental settings including adoptive transfer.

PMID- 8300157
TI  - Rejuvenated expression of H-2Kb in RMA-S cells does not affect alloreactive T
      cell- and natural killer cell-mediated lysis.
AB  - Reduced sensitivity to alloreactive cytotoxic lymphocytes (CTLs) and increased
      susceptibility to natural killer (NK) cells in vivo and in vitro are two
      phenotypic characteristics that have been attributed to the reduced major
      histocompatibility complex (MHC) ligand density on the surface of an antigen
      presentation-defective cell line, RMA-S. As RMA-S exhibits both defective
      processing of antigenic peptides and very low class I expression, it is uncertain
      which is responsible for the above characteristics. In this report, we show that
      the phenotype cannot be reversed by increasing the number of Kb + beta 2-M
      complexes expressed on the cell surface. These findings emphasize the importance
      of association of MHC class I molecules with endogenously processed peptides for
      biological interaction with alloreactive CTLs and NK cells.

PMID- 8300158
TI  - Nitric oxide mediates the toxoplasmastatic activity of murine microglial cells in
      vitro.
AB  - Toxoplasma gondii (T. gondii), an opportunistic protozoan, is an important cause
      of central nervous system (CNS) infections in immunosuppressed patients. The
      present study focused on the interaction between T. gondii and microglial cells
      from the brain of neonatal Balb/c mice. Preincubation of the murine microglial
      cells with recombinant interferon-gamma (rIFN-gamma) and lipopolysaccharide (LPS)
      induced significant inhibition of T. gondii replication in a dose dependent
      manner. This antiparasitic effect in microglial cells was correlated with the
      induction of the L-arginine-dependent generation of reactive nitrogen
      intermediates (RNIs). Tumor necrosis factor-alpha (TNF-alpha) was also involved
      in the toxoplasmastatic activity. Microglial cells incubated with recombinant TNF
      alpha in combination with a non-activating concentration of rIFN-gamma released
      substantial amount of RNIs. Neutralizing antibodies against mouse TNF-alpha
      inhibited the release of RNI by rIFN-gamma activated macrophages. In summary, the
      present results show that activation of microglial cells by rIFN-gamma and LPS
      induce the production of nitric oxide (NO) by these cells via an L-arginine
      dependent pathway. NO appears to be the effector molecule mediating the
      toxoplasmastatic effects in these cells.

PMID- 8300159
TI  - CD45-deficient RBL-2H3 cells. Cellular response to Fc epsilon R- and ionophore
      induced stimulation.
AB  - The CD45 protein is a transmembrane tyrosine phosphatase that is required for
      normal T and B cell receptor-mediated signaling. In order to study the function
      of this phosphatase in mast cells, we have isolated a CD45-deficient variant from
      the rat basophilic leukemia cell line (RBL-2H3), a tumor analog of mucosal mast
      cells. The secretory response as well as the inositol 1,4,5-triphosphate (InsP3)
      formation to Fc epsilon RI and ionophore stimuli were similar in the RBL-2H3 cell
      line and its derived CD45-deficient subpopulation. However, pretreatment with the
      phorbol ester TPA, which directly activates protein kinase C (PKC), caused a
      marked increase in mediator release and InsP3 production in the CD45-deficient
      variant compared to the parental RBL-2H3 cells. These findings suggest that CD45
      might directly or indirectly modify the activity of PKC or the InsP3
      dephosphorylating phosphatase.

PMID- 8300160
TI  - PNA lectin-based separation of thymocytes into mature and immature
      subpopulations: CD4-8- double negative cells display characteristics of PNAlo
      mature thymocytes.
AB  - Cortical (immature) thymocytes are widely reported to express intermediate to
      high levels of receptors for the lectin, peanut agglutinin (PNA). Light-scatter
      studies of murine fetal thymocytes stained with PNA or anti-mouse CD4 and CD8
      monoclonal antibodies indicated, however, that the most immature CD4-8- (DN)
      thymocyte subpopulation binds levels of PNA commonly described as PNAlo.
      Evaluation of the PNA binding characteristics of fetal thymocytes negative for
      the CD8 antigen confirmed the existence of a major population (approximately 20%
      of total cells) of CD4-8- PNAlo fetal thymocytes. The majority of these DN
      thymocytes were subsequently found to bind sub-agglutinating levels of PNA,
      similar to mature CD4+ or CD8+ single positive (SP) thymocytes. Given this
      information, an immunomodulating compound (2,3,7,8-tetrachlorodibenzo-p-dioxin;
      TCDD) known to produce a maturational delay in murine thymocytes was tested for a
      possible concurrent effect on thymocyte PNA lectin binding. A TCDD-induced
      increase in DN thymocytes was found to be paralleled by an increase of equal
      magnitude in PNAlo thymocytes. Taken together, these data provide evidence that
      acquisition of the PNA receptor may be a maturational event occurring during the
      DN stage of thymocyte ontogeny. Further, these results suggest that separation of
      thymocytes into mature (medullary) and immature (cortical) subpopulations by PNA
      agglutination may result in contamination of medullary cells by the most immature
      (DN) subpopulation of thymocytes.

PMID- 8300161
TI  - Partial amino acid sequence of monoclonal extracellular antigen-specific T cell
      proteins.
AB  - Antigen-specific molecules secreted by murine T cell hybrids (TABM) specific for
      4-hydroxy 3-nitrophenyl (NP) or azobenzenearsonate (ABA) were purified from
      ascitic fluid by ion exchange chromatography and/or affinity for antigen. Partial
      amino acid sequence of reduced Mr 72,000 NP-specific polypeptides and Mr 20,000
      peptides prepared by treatment of the ABA-specific immunoprotein with cyanogen
      bromide was obtained and a septapeptide of the NP-specific TABM shared 3/7
      residues with the ABA-specific TABM. Both TABM shared residues present in 95% T
      cell receptor for antigen (TCR) V alpha subgroup I and 83-96% murine
      immunoglobulin V kappa Fr3. These results provide evidence that extracellular
      antigen-specific T cell proteins are soluble analogues of TCR alpha chains and
      belong to the immunoglobulin supergene family.

PMID- 8300162
TI  - The role of cytokines in heat stroke.
AB  - Heat stroke is a disease characterized by high fever. Cytokines such as
      interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
      delta) play a major role in fever production. In the current studies, eight
      patients with heat stroke were enrolled in a cytokine studies. Serum cytokine
      levels of these patients were determined by EIA methods, and in vitro IL-1 and IL
      1 inhibitor production were determined by murine thymocyte proliferation assay
      and/or EIA. Significantly high levels of circulating IL-1, TNF-delta, and IL-6
      were demonstrated. Positive correlations were demonstrated between the body
      temperature and the level of IL-1 beta, and the cooling time and level of serum
      IL-1 beta. In addition, monocytes from heat stroke patients after complete
      recovery, secreted a much higher amount of IL-1 than did normal volunteers.
      However, there was no difference in IL-1 inhibitor production. These results
      indicate that cytokines may play a major role in the pathogenesis of heat stroke,
      and the ability to make different amounts of IL-1 in response to exogenous
      stimulation appear to be risk factors for an attack of heat stroke.

PMID- 8300163
TI  - Computers in the laboratory.

PMID- 8300164
TI  - Computerisation of blood bank services of a large hospital.
AB  - A comprehensive computer aided management scheme for Blood Bank of a large
      hospital is presented. The hardware requirement and networking pattern are simple
      flexible and cost effective to suit any kind of needs. Details of the modular
      software program are discussed. The advantages of the modular program is its
      flexibility and expandability, to suit not only the needs of a Blood Bank but
      also the whims and fancies of the personnel working in it. The program is
      completely portable and operates in an MS DOS environment on a IBM or compatible
      machine. The solutions are simple and cost-effective, a feature of particular
      importance to setups which have the technological capability but do not have the
      economic feasibility. The approach and software features are discussed in detail
      in order to make it possible for any one to develop similar system if desired.

PMID- 8300165
TI  - Isolation of Campylobacter from human and other sources in Bombay.
AB  - Out of 720 faecal samples studied from acute diarrhoeal patients comprising 645
      children and 75 adults, only 4 yielded Campylobacter strains. No Campylobacter
      was isolated from 300 control faecal samples. One isolate each of C. Coli and C.
      jejuni was obtained from faecal samples of chicken and goat respectively. No
      Campylobacter was isolated from 10 sewage samples studied.

PMID- 8300166
TI  - Relative efficacy of bone marrow trephine biopsy sections as compared to trephine
      imprints and aspiration smears in routine hematological practice.
AB  - The relative efficacy of trephine sections, trephine imprints and aspiration
      smears in yielding diagnostic and additional information was compared in 767 sets
      of bone marrow samples. Trephine sections were diagnostic in significantly more
      cases as compared to trephine imprints and aspiration smears (P < 0.001).
      Additional information was obtained in 326 trephine sections which was not
      available from trephine imprints and aspiration smears. Significantly more number
      of trephine sections provided diagnosis in case of dry tap/scanty material, for
      assessment of lymphoma-tumour infiltration, cellularity, Perl's reaction,
      megakaryocyte density and proliferating cell lines in myeloproliferative
      disorders. Fibrosis of bone marrow, pattern of bone marrow involvement and
      topographical alterations were appreciable only on trephine sections. The
      differential counts done on trephine imprints and aspiration smears correlated
      well and cytomorphological characterisation of immature cells (blasts and
      promyelocytes) could be done on these two preparations. Although trephine
      sections provide maximum information, all three preparations were found
      complementing each other and should be evaluated simultaneously for complete bone
      marrow interpretation.

PMID- 8300167
TI  - Granular cell tumor: a clinicopathological study.
AB  - Granular cell tumor is a relatively uncommon tumor of doubtful histogenesis.
      Nineteen cases of granular cell tumor reported in the department of Pathology,
      Kasturba Medical College, Mangalore, were analysed. Majority of tumors were seen
      in third to fifth decade mainly in females. The occurrence in rarer sites like
      caecum, of which only two cases have been so far reported tempted us to publish
      this study.

PMID- 8300168
TI  - Mycological aspects of dermatomycosis in Ludhiana.
AB  - 159 clinically diagnosed cases of dermatomycosis were examined and subjected to
      mycological study. In the direct microscopic examination, 78 (49.05%) cases were
      positive and cultures were positive in 66 (41.5%) cases. The common clinical
      presentation was T. corporis in 60 (37.7%) cases. The commonest species
      encountered was T. rubrum (42.42%) followed by Epidermophyton floccusum (15.15%),
      Candida (13.63%), T. violaceum (12.12%), T. mentagrophyte (6.06%) & T. tonsurans
      (1.5%) in this study. The prevalence of infection was more in males.

PMID- 8300169
TI  - Actinomyces species associated with intrauterine contraceptive devices and pelvic
      inflammatory disease.
AB  - Swabs from 112 removed intrauterine contraceptive devices (IUCD), endocervical
      swabs from these women and from 65 women with pelvic inflammatory disease (PID)
      were studied for actinomyces, using direct fluorescent antibody test and culture.
      Endocervical swabs from 50 control subjects were also studied. Actinomyces
      species could be detected in 23 (20.5 percent) of IUCD wearers and 8 (12.3
      percent) of patients with PID. In control cases, no actinomyces were detected.
      The isolation rate using a selective medium (Actino Blood Agar) was 71.4 percent.
      Actinomyces israelii, Actinomyces naeslundii and Actinomyces viscosus were
      isolated.

PMID- 8300170
TI  - Microbiological study of mycetoma patients from Bombay with special reference to
      actinomyces immunofluorescence.
AB  - 17 of the 21 clinically diagnosed mycetoma and actinomycosis cases studied
      yielded positive cultures. Foot, leg, inguinal region, chest wall, jaw and scalp
      were the affected sites. 15 of the patients were from Bombay, 13 of them had
      infection due to Nocardia species and 2 had Actinomyces israelii infection. The
      other two patients from South India had Madurella mycetomi infection.
      N.brasiliensis was commonest isolate (8). Other isolates were N.asteroides (2),
      N.pelletieri (2), N.caviae (1) and A.israelii (2). A direct fluorescent antibody
      test to detect actinomyces was used in selected cases (4). Two of whom gave
      positive immunofluorescence with A.israelii FITC labeled globulin, in primary
      smears as well as in cultures.

PMID- 8300171
TI  - The role of peroral fine needle aspiration cytology (FNAC) in the diagnosis of
      parapharyngeal lesions--a study of 51 cases.
AB  - The utility of peroral fine needle aspiration cytology (FNAC) in diagnosis of 51
      parapharyngeal lesions was studied from January, 1986 till May, 1991. The age of
      the patients ranged from 6 years to 85 years. Analysis of results showed 9
      inflammatory lesions, 22 benign tumours and 20 malignant tumours. Correlation
      with histopathology showed diagnostic accuracy of 90.2% with no false positive
      report. Review of FNAC of head and neck lesions showed hardly any publication on
      aspiration cytology of parapharyngeal masses.

PMID- 8300172
TI  - Correlation between membrane glycoprotein and detergent dissected membrane
      protein in the assessment of LMIF: a report of 51 ALA cases.
AB  - Assessment of 51 amoebic liver abscess cases for leukocyte migration inhibition
      factor released using membrane glycoprotein and detergent dissected membrane
      protein (DDMP) of axenic Entamoeba histolytica (NIH:200). Lymphokines release by
      T lymphocytes in response to purified amoebic membrane glycoprotein (PAMG)
      against whole amoebic lysate (WAL), dissect out protein against whole amoebic
      lysate and membrane glycoprotein against dissected protein was tested by
      leukocyte migration inhibition test on blood samples from proved amoebic liver
      abscess cases. A significant increase was noted in the release of lymphokines and
      100% positivity was observed with both PAMG and DDMP compared to 78% with whole
      amoebic lysate. The difference between means leukocyte migration indices of the
      membrane glycoprotein and whole amoebic lysate, detergent dissected protein and
      whole amoebic lysate with regards to release LMIF were found to be highly
      significant (P < 0.001), (P < 0.005) respectively. But insignificant difference
      and very much similarity was noted between the means of membrane glycoprotein and
      dissect out protein sensitized T lymphocytes with regards to lymphokine release
      in vitro. This shows the patients had high degree of leukocyte sensitized to pure
      amoebic membrane glycoprotein and detergent dissected membrane protein compared
      to whole amoebic lysate. These findings indicate that detergent dissected protein
      has similar antigenicity with membrane glycoprotein in elicitation cell mediated
      immune response in amoebic liver abscess cases.

PMID- 8300173
TI  - Biliary and serum immunoglobulin alterations in patients of cholelithiasis.
AB  - IgG, IgA and IgM were estimated in serum, common bile duct bile and gall bladder
      bile by single radial immunodiffusion technique in 30 patients of cholelithiasis,
      which included 22 patients of cholelithiasis with non functioning gall bladder
      (sub group A) and 8 patients of cholelithiasis with functioning gall bladder (sub
      group B). 30 age and sex matched controls were also included in the study. Serum
      IgG, IgA and IgM were significantly raised in patients of cholelithiasis as
      compared to controls. However, in gall bladder bile although IgA and IgM were
      significantly lower (more so in sub group A) than that of control group (p <
      0.001 and p < 0.001 respectively but there was no change in IgG. While in common
      bile duct bile, rise in all the three immunoglobulins was statistically
      insignificant when compared to controls.

PMID- 8300174
TI  - Bacteriology of bile in obstructive jaundice.
AB  - Bile from 25 patients with obstructive jaundice was cultured for both aerobic and
      anaerobic organisms. Twenty one samples were positive for culture. Mixed
      bacterial growth was seen in 5 (20%) of the bile samples 25 aerobes and one
      anaerobic were isolated. Escherichia coli was the commonest aerobic isolate and
      Bacteroides fragilis was the single anaerobe isolated. Majority of the aerobes
      isolated were sensitive to gentamycin.

PMID- 8300175
TI  - Possible role of streptokinase-induced delayed hypersensitivity and eosinophilia
      in pathogenesis of ankylosing spondylitis.
AB  - Present study relates to the results of investigations on 16 patients with
      Ankylosing spondylitis (AS). Age of the patients ranged from 16 to 44 (median 25)
      years. Male female ratio was 4.3:1. Sacroileitis was detected in all the
      patients. Seven patients each had stage 1 and 2 disease. Two other patients had
      stage 3 disease. Lower mean Hb per cent was detected among patients as compared
      to control groups. Twelve of 16 (75 per cent) patients had eosinophilia. HLA-B27
      antigen was detected in 10 of 16 (62.5 per cent) patients. Streptokinase-induced
      delayed sensitivity was detected in 10 of 16 (62.5 per cent) patients. Anti
      streptolysin 'O' antibodies were detected in 2 of 16 patients' sera. Moderate
      negative correlation was found between the size of induration of skin test and
      haemoglobin concentration (P < 0.05). Possibly, delayed hypersensitivity might
      induce both eosinophilia as well as anaemia among AS patients.

PMID- 8300176
TI  - Anaphylactoid transfusion reaction with anti-IgA antibodies in an IgA deficient
      patient: a case report.
AB  - A case of anaphylactoid transfusion reaction associated with anti-IgA antibodies
      is reported. The patient had low levels of serum IgA. She developed serious
      reaction characterised by erythematous rash, pruritus, cyanosis and dyspnoea
      after transfusion of otherwise compatible blood. Review of literature reveals
      that anaphylactoid transfusion reactions are very rare although frequency of anti
      IgA in general population is quite high. The IgA deficient donors (aIgA) form a
      unique resource of blood components for the clinical management of patients with
      anaphylactoid reactions caused by anti-IgA.

PMID- 8300177
TI  - Chorioangioma of placenta: report of 3 cases.
AB  - Chorioangiomas are commonest benign tumors of placenta, but those measuring more
      than 5 cms are rare. We present three cases of large chorioangiomas. Of the
      three, two cases were associated with hydramnios and premature labour.

PMID- 8300178
TI  - Eruptive vellus hair cysts: a case report.

PMID- 8300179
TI  - Leiomyosarcoma of urinary bladder: a case report.

PMID- 8300180
TI  - Sebaceous carcinoma of caruncle: a case report.

PMID- 8300181
TI  - Primary diagnosis of soft tissue echinococcosis by aspiration cytology.
AB  - A case of hydatid cyst of soft tissue diagnosed by Fine needle aspiration of a
      cyst is reported. The patient presented with gradually increasing swelling in the
      anterior-inferior aspect of shoulder. The provisional clinical diagnosis of cold
      abscess shoulder was made, patient was referred for Fine needle aspiration
      cytology (F.N.A.C.). Swelling was aspirated by 23-gauge needle obtaining 1.5 ml
      of blood-mixed fluid. Smears of fluid showed protoscolices, fully developed
      scolices with rostellum and scattered hooklets, pathognomonic of Echinococcosis.
      Histopathologic examination of surgically removed cyst showed chronically
      inflamed echinococcal cyst. No complication was observed.

PMID- 8300182
TI  - Heterotopic ossification in colorectal adenocarcinoma [corrected].
AB  - Heterotopic ossification in Adenocarcinomas of the colon is uncommon. The
      clinical presentation of these patients is similar to those without osseous
      metaplasia. Its importance lies in the fact that it may be misdiagnosed for a
      carcinosarcoma. Which has a poorer prognosis. These two cases are reported
      because of its rarity.

PMID- 8300183
TI  - Multilocular cystadenoma of the liver with mural nodules.
AB  - Hepatobiliary cystadenoma, characterised by the interposition of a mesenchymal
      stroma beneath the epithelium and the connective tissue layer, is a tumor
      described exclusively in women. These tumors have a potential for malignant
      transformation. Complete surgical excision is mandatory. We report a case
      cystadenoma with mesenchymal stroma (CMS), with mural nodules in the cyst wall,
      similar to those described in ovarian mucinous cystadenoma.

PMID- 8300184
TI  - Spindle cell haemangioendothelioma: a case report.

PMID- 8300185
TI  - Phaeomycotic cyst in a post-renal transplant patient.

PMID- 8300186
TI  - Cavernous hemangioma of the orbit: a case report.
AB  - Cavernous hemangioma is the most common benign intraorbital tumor in the young
      and middle aged, producing painless proptosis. It is common in females in whom it
      may enlarge during pregnancy. There have however been very few series reported on
      this entity.

PMID- 8300187
TI  - Expert systems for interpretive diagnosis in pathology.

PMID- 8300188
TI  - Morphology and distribution of astrocytes in the molecular layer of the dentate
      gyrus in NZB/BlNJ, Dreher, and C57BL/6J mice.
AB  - Numerous ectopic granule cells are found in the molecular layer of the dentate
      gyrus in NZB/BlNJ and dreher mutant mice. These ectopic neurons occur either
      singly or in small clusters. In contrast, few ectopic granule cells are seen in
      the dentate molecular layer of C57BL/6J mice and dreher control littermates. In
      this investigation we have examined the morphology, number, and distribution of
      molecular layer astrocytes in NZB/BlNJ, dreher homozygotes, dreher littermate
      controls, and C57BL/6J mice to determine the effect of the presence of ectopic
      granule cells. In the molecular layer of C57BL/6J mice and dreher control
      littermates, astrocytes have a typical stellate appearance with processes
      emanating in all directions. The arborization of astrocytes in areas devoid of
      ectopic granule cells in NZB/BlNJ mice and dreher homozygotes was similar to that
      in C57BL/6J mice and dreher control littermates. In contrast, the morphology of
      astrocytes in the immediate vicinity of ectopic granule cells or ectopic clusters
      was distinctly non-stellate. Furthermore, the somata and processes of these
      astrocytes occasionally appeared to make intimate contact with the ectopic
      granule cells. A quantitative analysis of the number and distribution of
      astrocytes in NZB/BlNJ vs C57BL/6J mice and dreher vs. control littermates
      indicated that these parameters were not altered by the presence of the ectopic
      neurons. We conclude that the trophic effects of ectopic neurons on glial cells
      can affect the growth and orientation of astrocytic processes without a
      concomitant effect on glial cell number.

PMID- 8300189
TI  - A monoclonal anti-idiotypic antibody to opioid receptors labels desipramine
      induced opioid binding sites on rat C6 glioma cells and attenuates thymidine
      incorporation into DNA.
AB  - Treatment of rat C6 glioma cells with the tricyclic antidepressant desipramine
      induces opioid binding. Here the distribution of these opioid-binding sites on C6
      cell membranes and a functional property were investigated. Immunohistochemical
      examination of C6 cells was performed using a monoclonal anti-idiotypic antibody
      to opioid receptors (Ab2AOR). Ab2AOR uniformly labeled > 97% of the cells exposed
      to desipramine over their entire surface. The opioid-receptor antagonist
      naltrexone completely blocked Ab2AOR binding. Ab2AOR, which has opioid agonist
      properties, also inhibited DNA synthesis in desipramine-treated but not in naive
      C6 cells. Similarly, morphine blocked C6 cell proliferation only after
      desipramine treatment. The antineurotrophic action of Ab2AOR was reversed by
      naltrexone and was insensitive to pertussis toxin. These findings demonstrate
      that Ab2AOR suppresses the proliferation of C6 glioma cells by binding to
      desipramine-induced opioid receptors.

PMID- 8300190
TI  - Vimentin immunoreactive glial cells in the fish optic nerve: implications for
      regeneration.
AB  - The poor regenerative ability of neurons of the central nervous system in
      mammals, as compared with their counterpart in fish or amphibians, is thought to
      stem from differences in their immediate nonneuronal environment and its response
      to axonal injury. We describe one aspect of the environmental response to axonal
      injury in a spontaneously regenerating system--the fish optic nerve. The aspect
      under investigation was the reaction of glial cells at the injury site. This was
      examined by the use of antibodies that specifically recognize vimentin in fish
      glial cells. In the present study, affinity-purified vimentin antibodies were
      raised against a nonconserved N-terminal 14-amino acid peptide, which was
      predicted from the nucleotide sequence of vimentin. These antibodies were found
      to react specifically with glial cells in vitro. Moreover, the antivimentin
      antibodies stained both the optic nerve and the optic tract, but with different
      patterns. Specificity of the antibodies was verified by protein immunoblotting,
      tissue distribution, and labeling patterns. After injury, vimentin
      immunoreactivity initially disappeared from the site of the lesion due to cell
      death. Early signs of glial cell migration toward the injury site were evident a
      few days later. It is suggested that the reappearance of vimentin-positive glial
      cells at the site of injury is associated with axonal elongation across it, and
      that they contribute to the regenerative ability of the fish optic nerve.

PMID- 8300192
TI  - Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity
      and glial ultrastructure in the rat neuroendocrine hypothalamus.
AB  - The influence of gonadal steroids on the ultrastructure of glial cells and on the
      immunoreactivity for the specific astrocytic marker glial fibrillary acidic
      protein (GFAP) has been assessed in the neuroendocrine hypothalamus. The
      following parameters were analyzed in the arcuate nucleus of adult female rats:
      the number and the surface density of cells immunoreactive for GFAP, the number
      of glial profiles showing bundles of glial filaments, the size of the bundles of
      glial filaments, and the proportion of neuronal perikaryal membrane apposed by
      glial processes. These parameters were studied during the different phases of the
      estrous cycle, after ovariectomy, and after the administration of estradiol or
      progesterone to ovariectomized rats. No significant differences were detected in
      the number of GFAP-immunoreactive cells among the different experimental groups.
      The surface density of GFAP-immunoreactive material, the number of glial profiles
      in the neuropil, and the proportion of neuronal perikaryal membrane covered by
      glia were increased in the afternoon of proestrus and in the morning of estrus
      compared with other phases of the estrous cycle or to ovariectomized rats and
      showed a rapid (5 h) and reversible increase in ovariectomized rats injected with
      17 beta estradiol, with a maximal effect by 24 h after the administration of the
      hormone. In contrast, the size of the bundles of glial filaments was decreased in
      the afternoon of proestrus, in the morning of estrus, and by the administration
      of estradiol to ovariectomized rats. The parameters studied were not affected by
      the administration of progesterone. However, progesterone (300 micrograms/rat)
      blocked the effects of 17 beta estradiol (1, 10, and 300 micrograms). The results
      suggest that glial cells may be actively involved in the modulation of
      neuroendocrine events by the hypothalamus.

PMID- 8300191
TI  - Novel relationships of growth factors to the G1/S transition in cultured
      astrocytes from rat forebrain.
AB  - The cell cycle encompasses the sequential events regulating cell division. In
      mammalian brain, initiation of astrocyte cycling is critical during development
      and injury. To investigate the timing of growth factor requirements as they
      commit to passing through the G1 phase, primary and secondary rat astrocytes were
      stimulated to enter the cycle after serum or growth factor deprivation.
      Bromodeoxyuridine immunofluorescence was used to monitor S phase nuclei after
      growth factor re-addition (at time 0). Cycle kinetics were identical whether
      quiescent cultures were exposed to 10% (vol/vol) calf serum, or to a defined
      medium containing fibroblast growth factor, insulin, and epidermal growth factor.
      The control point in late G1 that represents commitment to achieving the G1/S
      transition was identified by cycloheximide (CHX, 0.1 microgram/ml) addition.
      Sensitivity to cycle arrest by CHX disappeared at 9-10 h. In contrast, shift-down
      to growth factor-deficient medium arrested cell cycling virtually until G1/S (12
      h). With selective exposure during late G1 (9-12 h), no single agent permitted
      cycle progression. However, any two agents enabled cycling, and complementary or
      synergistic effects were apparent. These requirements were identical in astroglia
      from newborn and long-term cultures. Thus, temporal dissociation exists between
      the processes of escape from CHX sensitivity and from requirements for growth
      factors, two recognized hallmarks of commitment to cycle progression.
      Furthermore, simultaneous presence of at least two growth factors is necessary at
      or near G1/S. Both findings distinguish astrocytes from several other cell types.

PMID- 8300193
TI  - Restricted localization of L1 and N-CAM at sites of contact between Schwann cells
      and neurites in culture.
AB  - Schwann cell-axon contacts in developing and regenerating peripheral nerve in
      situ contain high levels of the recognition molecules L1 and N-CAM, while the
      molecules are not detectable at the ab-axonal cell surface of Schwann cells. To
      investigate whether Schwann cells, axons, or both contribute to the localization
      of the molecules at Schwann cell-axon contacts, a heterologous cell culture
      system consisting of Schwann cells from mice and neurons from chicken was
      investigated by immunoelectron microscopy using species-specific L1 and N-CAM
      antibodies. We showed that Schwann cells expressed both molecules only at sites
      of contact between Schwann cells and neurites and other Schwann cells. Schwann
      cells not in contact with other cells expressed both molecules on their entire
      cell surface. In contrast, neurites expressed G4, an L1-related molecule in
      chicken, on their entire cell surface independently of whether they were in
      contact with other cells or not. Thus, cultured Schwann cells localize L1 and N
      CAM selectively at cell contact sites and may thereby stabilize their attachment
      to the neighboring cellular partners.

PMID- 8300194
TI  - Regulation of C6 glioma cell steroidogenesis by adenosine 3',5'-cyclic
      monophosphate.
AB  - Incubation of C6 glioma cells in the presence of aminoglutethimide, an inhibitor
      of cholesterol metabolism, together with either adenosine 3',5'-cyclic
      monophosphate (cAMP) analogues or agents that increase cAMP synthesis, such as
      cholera toxin, forskolin, and isoproterenol, stimulated the rate of pregnenolone
      formation by their isolated mitochondria. This effect of cAMP was blocked by the
      antagonist (Rp)-cAMPS. The incorporation rate of mevalonolactone into
      pregnenolone was also increased by the stimulation of adenylyl cyclase activity
      in intact C6 cells. It is concluded that cAMP stimulates glial cell
      steroidogenesis by increasing the movement of the substrate, cholesterol, to the
      mitochondria, where it will be metabolized to pregnenolone by the side chain
      cleavage cytochrome P450 enzyme.

PMID- 8300195
TI  - Proteolytic activation of bacterial toxins: role of bacterial and host cell
      proteases.

PMID- 8300196
TI  - Induction of cytokines in phagocytic mammalian cells infected with virulent and
      avirulent Listeria strains.
AB  - The present paper analyzes the cytokine response of mouse macrophages during
      infection by Listeria monocytogenes. The use of different mutants of L.
      monocytogenes impaired in various steps of the infection process allowed us to
      dissect the cytokine response. Cytokine mRNA expression was detected by PCR
      assisted amplification of RNA extracted from macrophages after infection with
      different Listeria strains. An increase in the amount of mRNA for tumor necrosis
      factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-6
      was detected in P388D1 macrophages infected with L. monocytogenes at 4 h
      postinfection. Interestingly, only hemolytic strains of L. monocytogenes were
      able to induce IL-1 alpha, IL-6, and TNF-alpha mRNA. This indicated that the
      induction of these cytokine mRNAs requires entry of the listeriae into the host
      cell cytoplasm. In contrast, IL-1 beta was also induced by infection with
      nonhemolytic mutants of L. monocytogenes which remain entrapped within the
      phagosome. The levels of TNF, IL-1 alpha, and IL-6 found in the supernatants of
      Listeria-infected P388D1 macrophages generally correlated well with the induction
      of the respective mRNAs, but it became obvious that cytokine activity is also
      regulated through posttranscriptional mechanisms. In vitro induction of the
      cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha was also observed by
      infection of bone-marrow-derived macrophages with L. monocytogenes.

PMID- 8300197
TI  - Inhibition of in vitro erythropoiesis by soluble mediators in Plasmodium chabaudi
      AS malaria: lack of a major role for interleukin 1, tumor necrosis factor alpha,
      and gamma interferon.
AB  - By using erythropoietin-dependent proliferation of splenic erythroid cells as an
      in vitro erythropoiesis model system, we demonstrate that spleen cells from
      Plasmodium chabaudi AS-infected C57BL/6 mice potently inhibited erythroid cell
      proliferation. Inhibitory activity was detected in spleen cell conditioned media
      (SPCM) prepared from infected mice but not from uninfected mice. The inhibitory
      activity in SPCM was characterized as being heat sensitive, macromolecular, and
      host derived. The inhibitory activity was not reversed by increasing the
      erythropoietin concentration and was found to be specific for the late erythroid
      lineage. Mouse strains, which differ in their resistance to P. chabaudi AS
      infection, produced and responded to the inhibitory activity to a similar extent.
      Putative immune mediators, interleukin 1 alpha, interleukin 1 beta, and gamma
      interferon, were found to be potent inhibitors of erythroid cell proliferation.
      However, antibody neutralization experiments failed to demonstrate a major role
      for these cytokines in the inhibitory activity of SPCM. Our results suggest that
      the elaboration of inhibitor(s) of erythropoiesis in hemopoietic organs of
      Plasmodium-infected mice may impair erythroid regeneration. The identity of the
      inhibitory mediator(s) is presently unknown but is distinct from interleukin 1,
      tumor necrosis factor alpha, and gamma interferon.

PMID- 8300198
TI  - Protection against lethal bacterial infection in mice by monocyte-chemotactic and
      -activating factor.
AB  - Chemotactic factors regulate the recruitment of neutrophils, lymphocytes, or
      monocytes-macrophages to infectious and inflammatory sites. The purpose of this
      study was to determine whether monocyte-chemotactic and -activating factor (MCAF
      [MCP-1], a JE gene product) also influences the host defense mechanism against
      microbial infection. We evaluated the effect of recombinant human MCAF on the
      survival rate of mice systemically infected with Pseudomonas aeruginosa or
      Salmonella typhimurium. The administration of 2.5 micrograms of MCAF 6 h before
      infection completely protected the mice from lethal infection. Mice with
      cyclophosphamide-induced leukopenia exhibiting increased susceptibility to P.
      aeruginosa were also endowed with resistance by the same dose of MCAF.
      Administration of MCAF at -6 h was critical, since MCAF given either earlier or
      later than -6 h failed to rescue mice from lethal infection. The in vivo effect
      on the survival of mice paralleled the reduced recovery of viable P. aeruginosa
      or S. typhimurium from the peritoneal cavity, i.e., the number of recovered
      bacteria from the MCAF (2.5 micrograms per mouse)-treated mice was reduced to
      less than 2% of control mice for P. aeruginosa and 4% of control mice for S.
      typhimurium at 24 h. Since MCAF exhibited chemotaxis on murine macrophages as
      well as enhanced phagocytosis and killing of bacteria in vitro, the activation of
      macrophages, followed by the recruitment into the peritoneal cavity, is
      responsible for eliminating bacteria and thus enhancing the survival rate.

PMID- 8300199
TI  - Human antibody response to Clostridium difficile toxin A in relation to clinical
      course of infection.
AB  - This study investigated whether differences in fecal and serum antitoxin A
      antibody levels may account for the duration of Clostridium difficile-associated
      diarrhea (CDAD) and the occurrence of relapses. By an enzyme linked-immunosorbent
      assay, we tested 40 patients with CDAD including 25 patients without
      immunodeficiency and 15 patients receiving antineoplastic drugs. Two hundred
      eighty serum samples and 80 normal stool samples were investigated as controls.
      In nonimmunocompromised patients, serum immunoglobulin (IgG) and fecal IgA
      antitoxin A antibody titers were significantly higher in patients who suffered a
      single episode (n = 21) than in those with relapsing CDAD (n = 4) whose titers
      were at control levels. Of these 25 patients, eight suffered from diarrhea which
      lasted for more than 2 weeks. These patients had significantly lower serum- and
      feces-specific antibody levels than the others who presented symptoms of shorter
      duration. In cytostatic-treated patients, antitoxin A antibody levels were
      similar to controls, but relapses occurred in a single case. These data suggest
      an association between a defective humoral response to toxin A and a more severe
      form of C. difficile infection. They also indicate that other host-related
      factors control the severity of CDAD and remain to be elucidated.

PMID- 8300200
TI  - Mouse interleukin-1 receptor antagonist induced by Actinobacillus
      actinomycetemcomitans lipopolysaccharide blocks the effects of interleukin-1 on
      bone resorption and osteoclast-like cell formation.
AB  - We have reported that P388D1 cell line murine macrophages stimulated with
      lipopolysaccharide (LPS) from Actinobacillus actinomycetemcomitans release
      interleukin-1 (IL-1) inhibitor. The IL-1 inhibitor was purified from conditioned
      media of P388D1 cells stimulated with A. actinomycetemcomitans LPS for 72 h to
      homogeneity by a four-step procedure: acetic acid extraction from conditioned
      media; Bio-Gel P-60 gel filtration chromatography; DEAE-Sepharose CL-6B column
      chromatography; and reverse-phase high-performance liquid chromatography on a C18
      hydrophobic support. The purified IL-1 inhibitor gave a single band of protein
      with a molecular mass of 26 kDa on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The purified IL-1 inhibitor was a heat- and acid-stable protein
      that was inactivated by digestion with trypsin and reduction with dithiothreitol.
      This inhibitory factor suppressed the proliferation of C3H/HeJ mouse thymocytes
      and the proliferation of IL-1-dependent cell lines, D10.G4.1 and RPMI 1788,
      induced by IL-1. However, this inhibitor did not affect the proliferation of IL-2
      dependent CTLL-2 cells induced by IL-2, the proliferation of C3H/HeJ mouse
      thymocytes stimulated with a mitogenic dose of concanavalin A, and the
      proliferation of IL-6-dependent B9 cells induced by IL-6. Furthermore, the IL-1
      inhibitor significantly blocked stimulation of bone resorption in organ cultures
      of newborn mouse calvaria and inhibited the osteoclast-like cell formation in
      mouse marrow cultures. A monoclonal antibody prepared against the purified IL-1
      inhibitor reacted with mouse recombinant IL-1 receptor antagonist (rIL-1ra), and
      a polyclonal antibody to mouse rIL-1ra reacted with the IL-1 inhibitor by Western
      blot (immunoblot) analysis. These results indicate that the IL-1 inhibitor is an
      identical molecule to rIL-1ra, suggesting that the IL-1 inhibitor (IL-1ra)
      released by macrophages stimulated with LPS from A. actinomycetemcomitans may
      play an important mediative role in the development of periodontal disease.

PMID- 8300201
TI  - Cytopathic effect, plaque formation, and lysis of Ehrlichia chaffeensis grown on
      continuous cell lines.
AB  - Ehrlichiae are strict intracellular bacterial pathogens that parasitize
      leukocytes or other blood cells. Only six agents of the tribe Ehrlichieae,
      namely, Cowdria ruminantium, Neorickettsia helminthoeca, Ehrlichia risticii,
      Ehrlichia sennetsu, Ehrlichia canis, and Ehrlichia chaffeensis, have been adapted
      to growth in continuous cell lines. E. chaffeensis, the agent of human
      ehrlichiosis, has been cultured only in a cell line of canine origin. We adapted
      purified cell-free E. chaffeensis for growth in human embryonic lung (HEL)
      fibroblasts (HEL 299), green monkey kidney cells (Vero), and a human cervical
      epithelioid carcinoma (HeLa) cell line. We observed a cytopathic effect with both
      Vero cells and HEL cells and plaque formation with cellular lysis when infected
      Vero cells were cultured in agar. Human fibroblasts are already commonly used for
      the isolation of viruses, coexiellae, and rickettsiae. Furthermore, the
      capability of these cells to support the growth of ehrlichiae suggests that they
      may be useful for primary isolation of ehrlichiae as well. The cytopathic effect
      produced in Vero or HEL cells offers a very helpful indicator of the infection.
      Plaque formation in Vero cells is a new phenomenon not yet reported for
      ehrlichiae and will allow the titration of inocula and clonal purification of
      this bacterium.

PMID- 8300202
TI  - Induction of muscle-relaxing factor by staphylococcal alpha-toxin.
AB  - Brain tissue and serum from mice intracerebrally injected with 1 microgram of
      staphylococcal alpha-toxin contained elevated amounts of a naturally occurring
      brain tissue component(s) called muscle-relaxing factor (MRF). MRF induced
      reversible, generalized, flaccid paralysis of mice after intracerebral but not
      intraperitoneal or intravenous administration. MRF (i) was soluble in Hanks
      balanced salt solution and in acidified (pH 2) Hanks balanced salt solution, in
      which it partitions into ethyl acetate, acetone, and methanol; (ii) was separated
      from some pigments by thin-layer chromatography on silica gel plates; (iii) did
      not comigrate with prostaglandin and leukotriene standards during high-pressure
      liquid chromatography with a mu Bondapak fatty acid column; and (iv) did not
      contain amino acids, exhibit absorption maxima at a wavelength range of 210 to
      600 nm, or fluoresce when exposed to UV light. MRF has been detected in rabbit
      brain that has been stored frozen at -70 degrees C and has been enhanced in vitro
      in slices of both mouse and rabbit brain following incubation of the brain slices
      with staphylococcal alpha-toxin. Studies to identify the chemical nature of MRF
      and the mechanism by which, in mice, it induces reversible, flaccid paralysis of
      voluntary muscle are continuing.

PMID- 8300203
TI  - Development and characterization of recA mutants of Campylobacter jejuni for
      inclusion in attenuated vaccines.
AB  - Isogenic recA mutants of Campylobacter jejuni have been constructed for
      evaluation of their usefulness in attenuated vaccines against this major
      worldwide cause of diarrhea. The recA+ gene of C. jejuni 81-176 was cloned by
      using degenerate primers to conserved regions of other RecA proteins in a PCR.
      The C. jejuni recA+ gene encodes a predicted protein with an M(r) of 37,012 with
      high sequence similarity to other RecA proteins. The termination codon of the
      recA+ gene overlaps with the initiation codon of another open reading frame which
      encodes a predicted protein which has > 50% identity with the N terminus of the
      Escherichia coli enolase protein. A kanamycin resistance gene was inserted into
      the cloned recA+ gene in E. coli and returned to C. jejuni VC83 by natural
      transformation, resulting in allelic replacement of the wild-type recA gene. The
      resulting VC83 recA mutant displayed increased sensitivity to UV light and a
      defect in generalized recombination as determined by natural transformation
      frequencies. The mutated recA gene was amplified from VC83 recA by PCR, and the
      product was used to transfer the mutation by natural transformation into C.
      jejuni 81-176 and 81-116, resulting in isogenic recA mutants with phenotypes
      similar to VC83 recA. After oral feeding, strain 81-176 recA colonized rabbits at
      levels comparable to wild-type 81-176 and was capable of eliciting the same
      degree of protection as wild-type 81-176 against subsequent homologous challenge
      in the RITARD (removable intestinal tie adult rabbit diarrhea) model.

PMID- 8300204
TI  - Effects on virulence of mutations in a locus essential for hyaluronic acid
      capsule expression in group A streptococci.
AB  - Mucoid or highly encapsulated strains of group A streptococci have been
      associated both with unusually severe infections and with acute rheumatic fever.
      Previously, we described an acapsular mutant, TX4, derived from a mucoid M-type
      18 strain of a group A streptococcus by transposon mutagenesis (M. R. Wessels, A.
      E. Moses, J. B. Goldberg, and T. J. DiCesare, Proc. Natl. Acad. Sci. USA 88:8317
      8321, 1991). We now report studies further characterizing strain TX4 as well as
      an additional acapsular mutant, TX72. Strain TX4 was found to contain a 9.5-kb
      deletion of chromosomal DNA adjacent to the site of transposon Tn916 insertion.
      Cloned chromosomal DNA from TX4 flanking the transposon insertion site was used
      as a probe to demonstrate the presence of homologous regions in 11 of 11 wild
      type group A streptococcal strains of various M protein types. A second acapsular
      mutant, TX72, had a single transposon insertion and had no apparent deletion of
      chromosomal DNA. The Tn916 insertion in TX72 was mapped to the hasA locus
      (encoding hyaluronate synthase), which lies within the chromosomal region deleted
      in TX4. Strain TX72 was avirulent in mice and sensitive to phagocytic killing in
      vitro. Transduction of either the insertion-deletion mutation from TX4 or the
      simple insertion mutation from TX72 to a type 24 group A streptococcus strain
      also resulted in loss of capsule expression, demonstrating that a homologous
      region of the chromosome controls capsule expression in another serotype of group
      A streptococci. We conclude that the hyaluronic acid capsule plays an important
      role in virulence and that a region of the chromosome essential for capsular
      polysaccharide expression is conserved among diverse group A streptococcal
      strains.

PMID- 8300205
TI  - M protein mediates streptococcal adhesion to HEp-2 cells.
AB  - Streptococcus pyogenes adheres to human epithelial cells in vitro and in vivo. To
      identify adhesins, cell wall components were extracted from S. pyogenes M6 with
      alkali or by treatment with mutanolysin and lysozyme. HEp-2 cells were incubated
      with extracts of S. pyogenes M6 and then analyzed by Western blot (immunoblot)
      assays, using antibodies to S. pyogenes. Only one streptococcal component (62
      kDa) was bound to HEp-2 cells and was identified serologically as M6 protein.
      Experiments with pepsin-cleaved fragments of M protein indicated that the binding
      site was located at the N-terminal half of the molecule. M protein was bound
      selectively to two trypsin-sensitive surface components, 97 and 205 kDa, of HEp-2
      cells on nitrocellulose blots of sodium dodecyl sulfate-polyacrylamide gels.
      Tritium-labeled lipoteichoic acid bound to different HEp-2 cell components, 34
      and 35 kDa, in a parallel experiment, indicating that lipoteichoic acid was not
      complexed with M protein and does not mediate M-protein binding. The four HEp-2
      components were unrelated to fibronectin since they did not react with specific
      antibodies. An M-protein-deficient (M-) strain of streptococcus (JRS75), grown in
      chemically defined medium, showed 73% less adhesion activity to HEp-2 monolayers
      than an M+ strain (JRS4). Streptococcal adhesion was insensitive to competitive
      inhibition by selected monosaccharides. These results indicate that M protein
      binds directly to certain HEp-2 cell membrane components and mediates
      streptococcal adhesion.

PMID- 8300206
TI  - Interleukin-1 is involved in mouse resistance to Mycobacterium avium.
AB  - In this study, we examined the contribution of the monokine interleukin-1 (IL-1)
      in mouse resistance to the intracellular pathogen Mycobacterium avium. The effect
      of neutralizing endogenous IL-1 in mouse macrophage resistance to M. avium
      infection was investigated. Infection of mouse peritoneal macrophages with M.
      avium B101 was shown to result in significant IL-1 beta release by cells at 4 and
      7 days postinfection. Addition of IL-1 receptor antagonist (IL-1ra) at doses of 5
      micrograms daily, which neutralized endogenous IL-1, failed to significantly
      modify the intracellular growth of M. avium. Mice were injected with M. avium
      B101 by the intravenous route, and the growth of the mycobacteria was monitored
      in the organs of intact mice and in those of mice that received repeated high
      doses of IL-1ra. The infection with M. avium elicited the production of large
      amounts of IL-1 in the lungs, livers, and spleens. Repeated injections of IL-1ra
      into M. avium-infected mice resulted in moderately enhanced growth of the bacilli
      in the livers and spleens but in much enhanced growth in the lungs. The enhanced
      growth of M. avium in the lungs correlated with a diminished inflammatory influx
      of cells (particularly neutrophils) in the bronchoalveolar space. These data
      argue for a role for IL-1 in host resistance to M. avium infections.

PMID- 8300207
TI  - Differential induction of tumor necrosis factor alpha in murine and human
      leukocytes by Mycoplasma arthritidis-derived superantigen.
AB  - Mycoplasma arthritidis-derived superantigen (MAS) is exclusively produced by M.
      arthritidis, which is the only known mycoplasma to produce a superantigen. As a
      superantigen, MAS shows properties similar to those of the staphylococcal
      enterotoxins and related substances, such as binding to major histocompatibility
      complex (MHC) class II and V beta-specific stimulation of T cells. In this series
      of experiments, we demonstrate some differences between MAS and other
      superantigens. MAS induced the production of tumor necrosis factor alpha (TNF
      alpha) mRNA in human as well as in murine leukocytes. However, only in murine
      leukocytes was the mRNA adequately translated into the protein. In human
      peripheral blood mononuclear cells, we found only small amounts of TNF, whereas
      in murine spleen cells we detected levels more than three times higher. The
      proliferative response to MAS has been shown to be restricted to I-E alpha in the
      murine MHC. Furthermore, TNF was induced in I-E alpha+ bone marrow-derived
      macrophages by MAS. In these cells, MAS rapidly induced very high levels of TNF
      and the amounts of mRNA detected correlated to the amount of protein produced. In
      comparison with other superantigens, including the staphylococcal enterotoxins,
      toxic shock syndrome toxin 1, and exfoliative toxin A, the failure of MAS to
      induce TNF-alpha in human peripheral blood mononuclear cells is specific for MAS
      and not common to all superantigens. The direct activation of bone marrow-derived
      macrophages also seems to be specific for MAS. These data suggest that the
      induction of TNF-alpha by MAS is dependent on the strength of binding to the MHC
      class II molecule.

PMID- 8300208
TI  - Heritable susceptibility to severe Borrelia burgdorferi-induced arthritis is
      dominant and is associated with persistence of large numbers of spirochetes in
      tissues.
AB  - In human Lyme disease, symptoms with widely varying levels of severity have been
      observed. A mouse model of Lyme disease has been developed which allows analysis
      of mice with mild, moderate, and severe pathologies after inoculation with the
      spirochete Borrelia burgdorferi. To determine whether the differences in symptoms
      reflect differences in the number of spirochetes persisting in affected tissues,
      a sensitive PCR technique was developed to detect B. burgdorferi DNA in virtually
      any tissue of an infected mouse. This analysis, which detects DNA from as few as
      three spirochetes, revealed the presence of B. burgdorferi DNA in many tissues
      from severely arthritic C3H/HeJ mice as early as 1 week postinfection. The heart,
      ear, and ankle were particularly heavily infected, although B. burgdorferi DNA
      was also detected in spleen, liver, brain, kidney, bladder, uterus, and lymph
      nodes. In contrast, much lower levels of spirochete DNA were detected in tissues
      of infected BALB/c mice, which develop less severe arthritis when infected with
      B. burgdorferi than do C3H/HeJ mice. This difference was evident throughout the 5
      week analysis. A competitive PCR method allowed determination of the absolute
      number of spirochete gene sequences in infected tissues. Ankles and hearts from
      C3H/HeJ mice were found to harbor 10(7) copies of the B. burgdorferi ospA gene,
      while these tissues from BALB/c mice contained 5- and 10-fold less B. burgdorferi
      DNA, respectively. The genetic regulation of severe pathology was analyzed by
      infecting the offspring of a cross between C3H/HeJ and BALB/c mice. The F1 mice
      developed severe arthritis and contained high levels of Borrelia DNA in the heart
      and ankle, similar to the C3H/HeJ parent. These findings indicate that
      susceptibility to severe arthritis is a dominant trait and suggest that it may
      correlate with high levels of persisting spirochetes. Models of pathology in Lyme
      disease should take into consideration the fact that severity of pathology may be
      directly related to the number of organisms in infected tissues.

PMID- 8300209
TI  - Regulation of Actinobacillus actinomycetemcomitans leukotoxin expression:
      analysis of the promoter regions of leukotoxic and minimally leukotoxic strains.
AB  - The leukotoxin of Actinobacillus actinomycetemcomitans has been implicated as a
      virulence determinant in various human infections and is encoded by a multigene
      operon consisting of four known genes, designated ltxC, ltxA, ltxB, and ltxD. The
      ltx operon appears to be present in all A. actinomycetemcomitans strains, but
      levels of toxin expression vary greatly among strains. Thus, to gain a better
      understanding of the expression and regulation of the ltx operon, we have
      analyzed the ltx promoters of a highly toxic (JP2) and a minimally toxic (652)
      strain of A. actinomycetemcomitans. The nucleotide sequence of the JP2 ltx
      promoter contains -10 and -35 elements situated 350 bases upstream of ltxC, and
      primer extension of JP2 RNA confirmed that they are functional in vivo. However,
      a second primer extension product of 40 bases was present, and analysis of a
      series of truncated JP2 promoters fused to lacZ suggested that the region
      immediately upstream of ltxC also promotes transcription in Escherichia coli.
      These results suggest that two promoters may direct ltx expression in JP2. In
      addition, a small open reading frame capable of encoding a peptide of 78 amino
      acids was identified upstream of ltxC. Northern blots showed that this open
      reading frame is transcribed as part of a 4.2-kb mRNA, a transcript not
      previously identified as being derived from the ltx operon. In contrast, strain
      652 expresses low steady-state levels of ltx mRNA, and its intact ltx promoter
      was inefficient in transcribing lacZ in E. coli. The nucleotide sequence of the
      652 promoter is similar to that of the JP2 promoter but contains a region of 530
      bp that is not present in JP2. Of 15 additional strains of A.
      actinomycetemcomitans that were analyzed, 13 contained promoters resembling the
      652 sequence and 2 possessed JP2-like promoters. Both strains possessing the JP2
      like promoter expressed 10- to 20-fold-higher levels of leukotoxin than did the
      strains possessing promoters resembling the 652 promoter. These results suggest
      that high levels of leukotoxin expression may correlate with the presence of the
      JP2-like promoter.

PMID- 8300210
TI  - Normal human B lymphocytes and mononuclear cells respond to the mitogenic and
      cytokine-stimulatory activities of Borrelia burgdorferi and its lipoprotein OspA.
AB  - Borrelia burgdorferi produces potent cell-activating molecules capable of
      stimulating polyclonal proliferation and immunoglobulin production by murine B
      lymphocytes and cytokine production by a variety of cell types. These stimulatory
      molecules function in infected mice, resulting in elevated levels of circulating
      immunoglobulins and serum interleukin-6. We have recently demonstrated that the
      purified outer surface lipoproteins OspA and OspB possess these properties. To
      assess their possible involvement in human disease, we determined whether cells
      from normal human donors could respond to these activities. Normal human B
      lymphocytes but not T lymphocytes proliferated when incubated with either
      sonicated B. burgdorferi or purified OspA. Sonicated B. burgdorferi was efficient
      at stimulating immunoglobulin M production by human mononuclear cell cultures;
      however, purified OspA was relatively inactive. Both sonicated B. burgdorferi and
      purified OspA stimulated production of high levels of interleukin-6 by
      mononuclear cells. These findings extend our observations with the mouse model
      and suggest that the stimulatory lipoproteins could indeed be involved in the
      symptoms and pathologies of human infection with B. burgdorferi.

PMID- 8300211
TI  - Antibacterial activity of hydrogen peroxide and the lactoperoxidase-hydrogen
      peroxide-thiocyanate system against oral streptococci.
AB  - In secreted fluids, the enzyme lactoperoxidase (LP) catalyzes the oxidation of
      thiocyanate ion (SCN-) by hydrogen peroxide (H2O2), producing the weak oxidizing
      agent hypothiocyanite (OSCN-), which has bacteriostatic activity. However, H2O2
      has antibacterial activity in the absence of LP and thiocyanate (SCN-).
      Therefore, LP may increase antibacterial activity by using H2O2 to produce a more
      effective inhibitor of bacterial metabolism and growth, or LP may protect
      bacteria against the toxicity of H2O2 by converting H2O2 to a less-potent
      oxidizing agent. To clarify the role of LP, the antibacterial activities of H2O2
      and the LP-H2O2-SCN- system were compared by measuring loss of viability and
      inhibition of bacterial metabolism and growth. The relative toxicity of H2O2 and
      the LP system to oral streptococci was found to depend on the length of time that
      the bacteria were exposed to the agents. During incubations of up to 4 h, the LP
      system was from 10 to 500 times more effective than H2O2 as an inhibitor of
      glucose metabolism, lactic acid production, and growth. However, if no more H2O2
      was added, the concentration of the inhibitor OSCN- fell because of slow
      decomposition of OSCN-, and when OSCN- fell below 0.01 mM, the bacteria resumed
      metabolism and growth. In contrast, the activity of H2O2 increased with time.
      H2O2 persisted in the medium for long periods of time because H2O2 reacted slowly
      with the bacteria and streptococci lack the enzyme catalase, which converts H2O2
      to oxygen and water. After 24 h of exposure, H2O2 was as effective as the LP
      system as an inhibitor of metabolism. H2O2 also caused a time-dependent loss of
      viability, whereas the LP system had little bactericidal activity. The
      concentration of H2O2 required to kill half the bacteria within 15 s was 1.8 M
      (6%) but fell to 0.3 M (1%) at 2 min, to 10 mM (0.03%) at 1 h, and to 0.2 mM
      (0.0007%) with a 24-h exposure. The results indicate that if high levels of H2O2
      can be sustained for long periods of time, H2O2 is an effective bactericidal
      agent, and the presence of LP and SCN- protects streptococci against killing by
      H2O2. Nevertheless, the combination of LP, H2O2, and SCN- is much more effective
      than H2O2 alone as an inhibitor of bacterial metabolism and growth.

PMID- 8300212
TI  - Fate of Listeria monocytogenes in murine macrophages: evidence for simultaneous
      killing and survival of intracellular bacteria.
AB  - The intracellular survival of the ubiquitous pathogen Listeria monocytogenes was
      studied in primary cultures of bone marrow-derived mouse macrophages. Bacteria
      were able to grow rapidly in these cells, with an apparent multiplication rate of
      about 40 min. Electron microscopy demonstrated that intracellular bacterial
      replication was the consequence of simultaneous intracellular killing and
      replication of bacteria in the same cells. Within the first hour following
      phagocytosis, most bacteria were destroyed in the phagosomal compartment to which
      they were confined. This was due to early transfer of hydrolytic enzymes to
      phagosomes, undoubtedly via phagosome-lysosome (P-L) fusion, as demonstrated by a
      quantitative analysis after staining for a lysosomal marker, acid phosphatase.
      One hour after infection, about 14% of the bacteria were free in the cytoplasm,
      in which they multiplied and induced actin polymerization and spreading to
      adjacent macrophages, as in epithelial cells. By using the 3-(2,4-dinitroanilino)
      3'-amino-N-methyldipropylamine staining procedure, direct evidence is presented
      that all phagosomes were acidified immediately after phagocytosis, thus
      indicating that intraphagosomal bacteria were exposed to an acidic environment
      that might favor vacuolar lysis by listeriolysin O. Intracellular growth in
      macrophages, therefore, appears to be the result of a competition between the
      expression of the hydrolytic activity of these cells following P-L fusion and the
      capacity of L. monocytogenes to escape from the acidified phagosomal compartment
      before P-L fusion has occurred. The finding that concomitant intracellular
      killing and survival of L. monocytogenes occurs in the same macrophages might
      explain the high immunogenicity observed in vivo with live bacteria, as opposed
      to killed bacteria.

PMID- 8300213
TI  - Construction and characterization of chromosomal insertional mutations of the
      Pseudomonas aeruginosa exoenzyme S trans-regulatory locus.
AB  - Exoenzyme S is an ADP-ribosyltransferase produced by Pseudomonas aeruginosa.
      Synthesis of exoenzyme S depends on an intact trans-regulatory locus encoding
      three protein products, ExsC, ExsB, and ExsA. To identify the phenotype of ExsC, 
      B, and -A mutants in exoenzyme S production, specific insertional mutations with
      the streptomycin resistance-encoding omega interposon were introduced into cloned
      DNA and returned to the chromosomes of P. aeruginosa PA103, PAO1, and PAK.
      Southern blot analysis was used to confirm insertion of omega and resolution of
      vector sequences. Exoenzyme S expression was measured in parental and mutant
      derivatives by Western blot (immunoblot) analysis and ADP-ribosyltransferase
      activity measurement. A complete set of mutations were obtained in strains PAK
      and PAO1, but in strain PA103, only an insertion in the exsA coding region was
      identified. Southern blot analysis demonstrated that extensive duplication and
      rearrangement of the PA103 chromosomal trans-regulatory locus occurred when
      exsC::omega or exsB::omega recombination events were attempted. Exoenzyme S
      antigen was not detectable in the supernatant or lysate fractions of mutant
      strains by Western blot analysis. ADP-ribosyltransferase activity was detected in
      the lysate but not in the supernatant fractions of mutant derivatives. The
      general secretion pathway appeared to function normally in mutant strains, as
      elastase, exotoxin A, and phospholipase C were measured in the supernatants of
      parental and mutant strains. Several differences were noted when the
      extracellular protein profiles of parental strains were compared with similar
      samples from the insertional mutant strains. Some of these differences appeared
      to be unrelated to exoenzyme S. These data suggest that insertional inactivation
      of the exoenzyme S trans-regulatory locus may affect a subset of other
      extracellular proteins.

PMID- 8300214
TI  - Macrophage permissiveness for Legionella pneumophila growth modulated by iron.
AB  - We have investigated the modulation of iron in two populations of macrophages
      which differ in susceptibility to Legionella pneumophila intracellular
      proliferation. Previously, we reported that thioglycolate-elicited peritoneal
      macrophages obtained from the inbred A/J mouse strain readily support the
      intracellular growth of L. pneumophila, while resident macrophages from the same
      strain do not. In this study, we show that A/J elicited macrophages exhibit
      markedly higher expression of transferrin receptor and intracellular iron content
      than A/J resident macrophages. Furthermore, apotransferrin and desferrioxamine
      inhibited the intracellular proliferation of L. pneumophila in elicited
      macrophages, and this suppression was reversed by the additions of Fe-transferrin
      or ferric nitrilotriacetate. Fe-transferrin and ferric nitrilotriacetate did not
      further increase the intracellular proliferation of L. pneumophila in
      thioglycolate-elicited macrophages. However, ferric citrate and ferric
      nitrilotriacetate stimulated in a dose-dependent manner the growth of L.
      pneumophila in resident macrophages. Furthermore, equimolar concentrations of
      desferrioxamine reversed the stimulatory effect of iron in these resident cells.
      These data provide evidence supporting the hypothesis that differences in
      susceptibility to L. pneumophila growth between permissive elicited macrophages
      and nonpermissive resident macrophages from the A/J mouse strain are due to
      intracellular availability of iron.

PMID- 8300215
TI  - Quantitative studies of invasion of rabbit ileal mucosa by Salmonella typhimurium
      strains which differ in virulence in a model of gastroenteritis.
AB  - An asymmetric organ culture system in which ileal tissues, freshly removed from
      rabbits, can be maintained structurally and functionally for up to 4 h has been
      developed. The composition of the solutions used to maintain ileal tissue in
      vitro were as follows. The serosal surface was bathed in the World Health
      Organization (WHO) rehydration formulation: NaCl, 60 mM; NaHCO3, 30 mM; KCl, 20
      mM; and glucose, 111 mM. The mucosal surface was bathed in the same solution with
      two important changes: all the sodium was replaced by choline, which is not
      absorbed, and tissue culture medium (consisting of commercial minimal essential
      medium to which was added fetal calf serum and glutamine to final concentrations
      of 10% [vol/vol] and 2.0 mM, respectively) was added to the choline-containing
      medium to a final concentration of 10% (vol/vol). The initial invasiveness (first
      2 h) of seven strains of Salmonella typhimurium differing in virulence (defined
      in terms of clinical origin or the ability to induce fluid loss in monkeys or
      rabbit ileal loops) was assessed quantitatively in an in vitro invasion assay
      with the organ culture system. The virulent strains (TML, W118, and WAKE) were
      found to be about 25- to 100-fold more invasive than the avirulent strains
      (SL1027, M206, LT7, and Thax-1). Thus, a clear correlation between initial
      mucosal invasion and virulence of S. typhimurium in a model which is relevant to
      human gastroenteritis was established. This is the first time, to our knowledge,
      that quantitative studies of invasiveness have been carried out in vitro on
      freshly isolated functioning gut.

PMID- 8300216
TI  - Differences in complement activation between complement-resistant and complement
      sensitive Moraxella (Branhamella) catarrhalis strains occur at the level of
      membrane attack complex formation.
AB  - The mechanism of resistance to human complement-mediated killing in Moraxella
      catarrhalis was studied by comparing different complement-sensitive and
      complement-resistant M. catarrhalis strains in a functional bystander hemolysis
      assay and an enzyme-linked immunosorbent assay (ELISA) for soluble terminal
      complement complexes. Complement-resistant stains appeared to activate complement
      to the same extent as, or even slightly better than, complement-sensitive
      strains. This indicates that complement-resistant strains do not inhibit
      classical or alternative pathway activation but interfere with complement at the
      level of membrane attack complex formation. A clear difference in dose-response
      curves for resistant and sensitive strains was observed both in the bystander
      hemolysis assay and in the ELISA. Complement-resistant strains showed optimum
      curves, whereas complement-sensitive strains gave almost linear curves. We
      conclude that resistant strains bind and/or inactivate one of the terminal
      complement components or intermediates involved in membrane attack complex
      formation. Trypsin, known to abolish complement resistance, changed the optimum
      dose-response curve of a resistant strain to a linear one, which strongly
      suggests that complement resistance is mediated by an M. catarrhalis-associated
      protein. This protein acts directly or through the binding of a terminal
      complement inhibitor present in serum.

PMID- 8300217
TI  - Nonmotility and phagocytic resistance of Pseudomonas aeruginosa isolates from
      chronically colonized patients with cystic fibrosis.
AB  - Although Pseudomonas aeruginosa chronically colonizes most older patients with
      cystic fibrosis (CF), bacterial features responsible for its persistence are
      understood poorly. We observed that many P. aeruginosa isolates from chronically
      colonized patients were nonmotile and resistant to phagocytosis by macrophages.
      P. aeruginosa isolates were collected from 20 CF patients for up to 10 years.
      Isolates from early colonization were highly motile and expressed both flagellin
      and pilin. However, many isolates from chronically colonized patients lacked
      flagellin expression and were nonmotile; a total of 1,030 P. aeruginosa CF
      isolates were examined, of which 39% were nonmotile. Moreover, sequential
      isolates recovered from several of the CF patients were consistently nonmotile
      for up to 10 years. Lack of motility was rare among environmental isolates (1.4%)
      and other clinical isolates (3.7%) of P. aeruginosa examined. Partial
      complementation of motility in nonmotile P. aeruginosa isolates was achieved by
      introduction of extra copies of the rpoN locus carried on plasmid pPT212,
      indicating that the alternate sigma factor, RpoN, may be involved in the
      coordinate regulation of virulence factors during CF infection. We hypothesize
      that the nonmotile phenotype may provide P. aeruginosa a survival advantage in
      chronic CF infection by enabling it to resist phagocytosis and conserve energy.

PMID- 8300218
TI  - The specific activities of Shiga-like toxin type II (SLT-II) and SLT-II-related
      toxins of enterohemorrhagic Escherichia coli differ when measured by Vero cell
      cytotoxicity but not by mouse lethality.
AB  - Characteristically, enterohemorrhagic Escherichia coli (EHEC) strains produce
      Shiga-like toxin type I (SLT-I), SLT-II, or both of these immunologically
      distinct cytotoxins. No antigenic or receptor-binding variants of SLT-I have been
      identified, but a number of SLT-II-related toxins have been described. Because
      EHEC O91:H21 strain B2F1, which produces two SLT-II-related toxins, is
      exquisitely virulent in an orally infected, streptomycin-treated mouse model
      (oral 50% lethal dose [LD50], < 10 organisms), we asked whether the pathogenicity
      of strain B2F1 was a consequence of SLT-II-related toxin production. For this
      purpose, we compared the lethality of orally administered E. coli DH5 alpha
      (Strr) strains that produced different cytotoxic levels of SLT-II, SLT-IIvha
      (cloned from B2F1), SLT-IIvhb (also cloned from B2F1), or SLT-IIc (cloned from
      EHEC O157:H7 strain E32511) on Vero cells. We also calculated the specific
      activities of purified SLT-IIvhb and SLT-II in intraperitoneally injected mice
      and on Vero cells. The two purified toxins were equally toxic for mice, but SLT
      IIvhb was approximately 100-fold less active than SLT-II on Vero cells and bound
      to the glycolipid receptor Gb3 with lower affinity than did SLT-II. In addition,
      characterization of SLT-II-related toxin-binding (B) subunit mutants generated in
      this study revealed that the reduced in vitro cytotoxic levels of the SLT-II
      related toxins were due to Asn-16 in the B subunit. Taken together, these
      findings do not support the idea that B2F1 is uniquely virulent because of the in
      vivo toxicity of SLT-II-related toxins but do demonstrate differences in in vitro
      cytotoxic activity among the SLT-II group produced by human EHEC isolates.

PMID- 8300219
TI  - Protective immunity to Brucella ovis in BALB/c mice following recovery from
      primary infection or immunization with subcellular vaccines.
AB  - Experiments were performed with BALB/c mice to elucidate the roles of humoral and
      cell-mediated immune responses in the acquisition of protective immunity to
      Brucella ovis and to compare infection immunity with immunity developed through
      vaccination with a hot saline extract (HS) of B. ovis. Mice convalescing from a
      primary infection with B. ovis displayed a high level of resistance to
      reinfection, as evidenced by splenic bacterial counts decreased over 10,000-fold
      from control groups at 2 weeks after challenge. Passive transfer assays revealed
      that protection was mediated by both T lymphocytes and antibodies but that
      antibodies had a substantially greater role on the basis of log units of
      protection that were transferred. Antibodies specific for HS proteins in sera
      from convalescent mice were predominantly of the immunoglobulin G 2a and 3
      isotypes. Vaccination with HS conferred good protection against B. ovis, but
      protection was greatly enhanced by the incorporation of QS-21 or other adjuvants.
      Protection provided by the HS vaccine resulted largely from immune responses to
      its protein moieties. A critical evaluation of the protective efficacy of the
      rough lipopolysaccharide component of HS was precluded by its poor immunogenicity
      in BALB/c mice. HS-QS-21 afforded protection against challenge infection with B.
      ovis as good as that which developed after a primary infection and as good as or
      better than that provided by attenuated Brucella melitensis vaccine strain Rev 1.
      Passive transfer experiments confirmed that the magnitudes of both humoral and
      cell-mediated forms of protective immunity were equivalent in mice vaccinated
      with HS-QS-21 and those recovering from a primary infection. Protective immunity
      to B. ovis in mice therefore resembled that to Brucella abortus, except that the
      relative roles of humoral and cell-mediated immunity, rather than being
      equivalent, were shifted toward a greater role for antibodies.

PMID- 8300220
TI  - Effect of tracheal cytotoxin from Bordetella pertussis on human neutrophil
      function in vitro.
AB  - The infiltration of neutrophils which phagocytose and kill microorganisms is an
      important defense mechanism against infections of the airways. Bordetella
      pertussis is a human respiratory pathogen which colonizes ciliated epithelium,
      causing whooping cough. We have investigated the effects of the peptidoglycan
      fragment tracheal cytotoxin (TCT) of B. pertussis on human neutrophil function in
      vitro. TCT (10(-6) to 10(-8) M) was toxic for human neutrophils, as measured by
      lactate dehydrogenase release and levels of intracellular ATP. TCT (10(-9) to 10(
      15) M) did not stimulate neutrophil migration or chemiluminescence and did not
      affect neutrophil phagocytosis. Incubation of neutrophils for 20 min with TCT
      (10(-9) to 10(-11) M) significantly inhibited (P < 0.05) their subsequent
      migration toward the chemotactic factor N-formyl-L-methionyl-L-leucyl-L
      phenylalanine (FMLP; 10(-9) M). Incubation of neutrophils for 20 min with TCT
      (10(-9) to 10(-15) M) significantly inhibited (P < 0.05) chemiluminescence
      stimulated by FMLP (10(-5) M). TCT (10(-6) to 10(-12) M) did not stimulate
      interleukin-1 alpha production by neutrophils or serum complement activation by
      the alternate pathway. We conclude that TCT at concentrations of < 10(-8) M
      affects important neutrophil functions and at higher concentrations is toxic. TCT
      may therefore contribute to the survival of B. pertussis within the airways in
      vivo.

PMID- 8300221
TI  - Human immunodeficiency virus type 1 infection of human macrophages modulates the
      cytokine response to Pneumocystis carinii.
AB  - The present studies examined production of the cytokines tumor necrosis factor
      alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 by human monocyte
      derived macrophages exposed to Pneumocystis carinii in vitro and the impact of
      concurrent macrophage infection with human immunodeficiency virus type 1 (HIV-1)
      on these cytokine responses. Macrophages were infected with the HIV-1 BaL
      monocytotropic strain for 10 to 14 days and then exposed to P. carinii. At
      various times following P. carinii treatment, culture supernatants were harvested
      to assess the cytokine profile. Addition of P. carinii to HIV-uninfected
      macrophages resulted in augmented production of IL-6, TNF-alpha, and IL-1 beta
      protein. By contrast, in HIV-infected macrophages exposed to P. carinii, only the
      release of IL-6 was increased compared with that for HIV-uninfected macrophages,
      while the levels of TNF-alpha and IL-1 beta decreased. This altered response was
      confirmed at the molecular level for TNF-alpha mRNA. Preventing physical contact
      between P. carinii and macrophages by a membrane filter inhibited all cytokine
      release. Substituting P. carinii with a preparation of P. carinii 95- to 115-kDa
      major membrane glycoprotein A yielded a response similar to that obtained by
      addition of intact P. carinii. These results suggest that HIV-1 infection of
      human macrophages modulates cytokine responses to P. carinii.

PMID- 8300222
TI  - Molecular cloning, characterization, and expression in Escherichia coli of iron
      superoxide dismutase cDNA from Leishmania donovani chagasi.
AB  - A cDNA corresponding to superoxide dismutase (SOD; EC 1.15.1.1.) was isolated
      from a Leishmania donovani chagasi (L. d. chagasi) promastigote cDNA library,
      using PCR with a set of primers derived from conserved amino acids of manganese
      SODs (MnSODs) and iron SODs (FeSODs). Comparison of the deduced amino acid
      sequences with previously reported SOD amino acid sequences revealed that the L.
      d. chagasi 585-bp open reading frame had considerable homology with FeSODs and
      MnSODs. The highest homology was shared with prokaryotic FeSODs. The coding
      region of L. d. chagasi SOD cDNA has been expressed in fusion with glutathione-S
      transferase, using an Escherichia coli mutant, QC779, lacking both MnSOD and
      FeSOD genes (sodA and sodB). Staining of native polyacrylamide gels for SOD
      activity of Leishmania crude lysate and the recombinant SOD revealed that both
      had SOD activity that was inactivated by 5 mM hydrogen peroxide but not by 2 mM
      potassium cyanide, which is indicative of FeSOD. The recombinant enzyme also
      protected E. coli mutant QC779 from paraquat toxicity. This indicated that the
      glutathione-S-transferase peptide does not interfere with the in vivo and in
      vitro activities of the recombinant SOD. Cross-species hybridization showed that
      FeSOD is highly conserved in the Leishmania genus. Interestingly, the
      hybridization pattern of the FeSOD gene(s) coincided with other classification
      schemes that divide Leishmania species into complexes. The cloning of FeSOD cDNA
      may contribute to the understanding of the role of SODs in Leishmania
      pathogenesis.

PMID- 8300223
TI  - Bacterium-host cell interactions at the cellular level: fluorescent labeling of
      bacteria and analysis of short-term bacterium-phagocyte interaction by flow
      cytometry.
AB  - Flow cytometry is a potentially powerful tool for analyzing the interactions of
      facultative intracellular bacteria and macrophages on a cellular level,
      particularly when fluorochromes are used to label the bacteria. We labeled
      Listeria monocytogenes and Salmonella typhimurium with a lipophilic dye, PKH-2,
      and used flow cytometry to investigate phagocytosis by J774A.1 cells and short
      term bacterial survival. Labeled and unlabeled bacteria were identical in terms
      of viability, growth kinetics, and survival within macrophages, although recovery
      per macrophage was much greater for L. monocytogenes than for S. typhimurium.
      Using L. monocytogenes as a prototypical facultative intracellular bacterium, we
      estimated bacterial survival during phagocytosis on the basis of linear
      fluorescence measurements of infected J774A.1 cells and recovery of L.
      monocytogenes from sorted cells. The lower percentage of surviving L.
      monocytogenes in macrophages containing higher bacterial loads indicated the
      accumulation of nonviable bacteria within phagocytes. Removal of the external
      source of viable bacteria by washes and gentamicin treatment reduced the
      percentage of surviving intracellular L. monocytogenes to a baseline level, and
      all baseline levels were similar, regardless of bacterial load. Listeria
      enrichment recoveries, derived from individually sorted J774A.1 cells,
      demonstrated the heterogeneity of macrophages in intracellular bacterial
      survival, especially within heavily infected cells. These results indicated that
      survival of L. monocytogenes was dependent on the adaptations of a small fraction
      of bacteria within a population of macrophages which permit intracellular growth.

PMID- 8300224
TI  - Recombinant murine gamma interferon stimulates macrophages of the RAW cell line
      to inhibit intracellular growth of Histoplasma capsulatum.
AB  - Macrophages of the RAW 264.7 cell line, activated by pretreatment with
      recombinant murine gamma interferon, inhibit the intracellular growth of
      Histoplasma capsulatum. Growth inhibition occurred by a mechanism that was
      operative only when L-Arg metabolism was allowed to occur. When activated
      macrophages were cultured in the absence of L-Arg or in the presence of NG
      monomethyl-L-Arg, a competitive inhibitor of L-Arg metabolism, activation to the
      antihistoplasma growth-inhibitory state did not occur. An increase in levels of
      NO2-, an end product of L-Arg metabolism, was detected only after activation of
      RAW 264.7 cells to the growth-inhibitory state. In contrast, only baseline levels
      of NO2- were detected when L-Arg was excluded or when NG-monomethyl-L-Arg was
      added to the culture medium. Nitric oxide (NO.), a reactive intermediate product
      of L-Arg metabolism, was implicated as the relevant antihistoplasma effector
      molecule. When H. capsulatum yeast cells were cultured for 24 to 28 h in a system
      designed to generate soluble NO., a dose-dependent cytotoxic effect was observed.

PMID- 8300225
TI  - Cellular and humoral immune responses to well-defined blood stage antigens (major
      merozoite surface antigen) of Plasmodium falciparum in adults from an Indian zone
      where malaria is endemic.
AB  - Conserved and variant regions of two blood stage vaccine candidate antigens of
      Plasmodium falciparum, merozoite surface antigen (MSA-1) and ring-infected
      erythrocyte surface antigen (Pf155/RESA), have been shown to be immunogenic.
      However, the relative immunogenicity of these immunogens in different populations
      has not been studied. The conserved N-terminal region of MSA-1 was investigated
      for its immunogenicity by studying cellular (T cell) and humoral (B cell) immune
      responses in P. falciparum-primed individuals, living in malaria-hyperendemic
      areas (Orissa State, India), where malaria presents an alarming situation. MSA-1
      derived synthetic peptides contained sequences that activated T cells to
      proliferate and release gamma interferon in vitro. There was considerable
      variation in the responses to different peptides. However, the highest responses
      (51% [18 of 35] by proliferation and 34% [12 of 35] by gamma interferon release)
      were obtained with a synthetic hybrid peptide containing sequences from conserved
      N- and C-terminal repeat regions of MSA-1 and Pf155/RESA, respectively. Antibody
      reactivities in an enzyme immunoassay of plasma samples from these donors to
      different peptides used for T-cell activation were heterogeneous. In general,
      there was poor correlation between DNA synthesis and either gamma interferon
      release or antibody responses in individual donors, underlining the importance of
      examining several parameters of T-cell activation to assess the total T-cell
      responsiveness of a study population to a given antigen. However, the results
      from our studies suggest that synthetic constructs containing sequences from the
      N- and C-terminal regions of MSA-1 and Pf155/RESA representing different
      erythrocytic stages of the P. falciparum parasite are more immunogenic in humans
      living in malaria-hyperendemic areas of India who have been primed by natural
      infection.

PMID- 8300226
TI  - Interleukin-6 (IL-6) production in mice infected with Trypanosoma cruzi: effect
      of its paradoxical increase by anti-IL-6 monoclonal antibody treatment on
      infection and acute-phase and humoral immune responses.
AB  - Trypanosoma cruzi infection of mice triggered endogenous production of
      interleukin-6 (IL-6) during the ascending phase of parasitemia. Injections of
      anti-IL-6 monoclonal antibody in infected mice at the time of the serum IL-6 peak
      paradoxically increased IL-6 levels to 60- to 80-fold those in infected mice
      receiving unrelated immunoglobulins. This early and transient increase in
      circulating IL-6 levels modified neither the immunoglobulin nor T. cruzi-specific
      antibody levels of immunoglobulin G1 (IgG1), IgG2a, IgG3, IgM, IgA, and IgE
      isotypes or the final outcome of infection nor the blood or tissular parasite
      levels. However, it tended to delay mortality of mice and to increase the levels
      of the acute-phase protein serum amyloid P component.

PMID- 8300227
TI  - Acquisition of heme iron by Neisseria meningitidis does not involve meningococcal
      transferrin-binding proteins.
AB  - Similarities in size between hemin-binding protein 1 (HmBP1) and transferrin
      binding protein 1 (TBP1) of Neisseria meningitidis suggest that these proteins
      are functionally homologous. However, a meningococcal mutant lacking the
      transferrin-binding proteins retained the capacity to acquire iron from heme and
      hemoglobin. In immunoblots, hyperimmune polyclonal antiserum against TBP1 did not
      react with HmBP1.

PMID- 8300228
TI  - Protection of human respiratory epithelium from Pseudomonas aeruginosa adherence
      by phosphatidylglycerol liposomes.
AB  - The ability of phosphatidylglycerol (DSPG) liposomes to prevent adherence of
      Pseudomonas aeruginosa to primary cultures of non-cystic fibrosis (CF) and delta
      F508 homozygous CF human respiratory epithelium was studied. The culture model
      was characterized by the simultaneous presence of various cellular phenotypes:
      well-differentiated respiratory epithelial cells, ciliated and nonciliated cells,
      and migrating cells which can be assimilated into a regenerating epithelium after
      injury. DSPG liposomes significantly decreased the binding of P. aeruginosa to
      migrating cells of both non-CF and delta F508 homozygous CF cultures compared
      with control cultures (35.5 x 10(-3) +/- 8.1 x 10(-3) bacteria per micron 2
      versus 23.9 x 10(-3) +/- 2.5 x 10(-3); P < 0.01 for non-CF cultures and 88.8 x
      10(-3) +/- 17.2 x 10(-3) bacteria per micron 2 versus 29.1 x 10(-3) +/- 0.6 x 10(
      3), P < 0.001 for CF cultures). After treatment with DSPG liposomes, the size of
      P. aeruginosa aggregates bound to migrating cells in both non-CF cultures and
      delta F508 homozygous CF cultures was significantly decreased (14.4 +/- 3
      bacteria per aggregate versus 11.9 +/- 2.5 bacteria per aggregate [P < 0.05] and
      29.9 +/- 8.4 bacteria per aggregate versus 17.3 +/- 2.3 bacteria per aggregate [P
      < 0.01], respectively). Moreover, the control cultures were characterized by a
      differential P. aeruginosa adherence according to both the cellular phenotype and
      the mutation. The migrating cells bound more bacteria than the stationary cells
      of both non-CF and delta F508 homozygous CF cultures. The CF migrating cells
      bound significantly more bacteria than the non-CF migrating cells (88.8 x 10(-3)
      +/- 17.2 x 10(-3) bacteria per microns 2 versus 35.5 x 10(-3) +/- 8.1 x 10(-3)
      bacteria per micron 2, P < 0.001). These results suggest that DSPG liposomes are
      able to decrease P. aeruginosa adherence to CF and non-CF respiratory epithelium,
      particularly to migrating cells, which mimic a regenerating epithelium after
      injury. DSPG liposomes could also represent a hydrophobic barrier limiting the
      deleterious action of P. aeruginosa exoproducts.

PMID- 8300229
TI  - Heterogeneous surface distribution of the fibrinogen-binding protein on Candida
      albicans.
AB  - As detected by indirect immunofluorescence and confocal microscopy, fibrinogen
      binding was heterogeneously distributed on the surface of Candida albicans. A low
      level of binding was generally observed homogeneously distributed on some yeast
      and most hyphal extensions of germ tubes. However, on most hyphal extensions,
      there were randomly distributed areas of increased expression, as revealed by
      patches of greater fluorescence intensity.

PMID- 8300230
TI  - Molecular cloning of an Onchocerca volvulus extracellular Cu-Zn superoxide
      dismutase.
AB  - Onchocerca volvulus, a human parasitic nematode, is the third leading cause of
      preventable blindness worldwide. This study describes the molecular cloning of a
      novel superoxide dismutase (SOD) from the parasite. This putative O. volvulus
      extracellular SOD (OvEcSOD) is 628 nucleotides (nt) long, including a 22-nt 5'
      spliced leader (SL1) and a portion encoding an N-terminal hydrophobic 42-amino
      acid signal peptide. The remainder of the cDNA shares 71% identity with an O.
      volvulus cytosolic SOD sequence and is 3 nt longer. All residues involved in
      metal ion binding, active site formation, folding, and dimer formation in SODs
      are conserved. Data indicate the OvEcSOD and O. volvulus cytosolic SOD are
      separate gene products and that the OvEcSOD appears to possess the
      characteristics of a membrane-bound or secreted enzyme which may be involved in
      the parasite defense against phagocyte-generated reactive oxygen species.

PMID- 8300231
TI  - Regulation of Clostridium perfringens alpha-toxin-activated phospholipase C in
      rabbit erythrocyte membranes.
AB  - The rapid phosphatidic acid (PA) formation induced by Clostridium perfringens
      alpha-toxin was stimulated by AlF4- in rabbit erythrocyte membranes. GTP[gamma S]
      [guanosine 5'-O-(3-thiotriphosphate)] stimulated the rapid 1,2-diacylglycerol
      formation and inositol 1,4,5-trisphosphate release induced by the toxin. On the
      other hand, treatment of erythrocyte lysates with phorbol 12-myristate 13-acetate
      (PMA) resulted in inhibition of toxin-induced PA production, and long-term PMA or
      1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) treatment of the lysates led
      to stimulation of PA formation. Furthermore, treatment of erythrocytes with the
      toxin caused an increase of protein kinase C activity in membrane fractions. The
      results suggest that toxin-induced PA formation is mediated by endogenous
      phospholipase C regulated through GTP-binding protein and protein kinase C in
      rabbit erythrocytes.

PMID- 8300232
TI  - Analysis of protective and nonprotective monoclonal antibodies specific for
      Bordetella pertussis lipooligosaccharide.
AB  - In this study, it has been determined that immunoglobulin G1 (IgG1) and IgG3
      monoclonal antibodies directed to the lipooligosaccharide A of Bordetella
      pertussis were able to protect mice from fatal aerosol infection. No correlation
      was found between the bactericidal activity in vitro in the presence of
      complement and the protection in mice, since a bactericidal IgG3 did not elicit
      protection. In addition, no significant difference in protective capacity was
      observed with bactericidal and nonbactericidal IgG1 antibodies, indicating that
      bactericidal activity is not a requirement for protection mediated by certain
      anti-lipooligosaccharide A antibodies. A reduction in protection in C5-deficient
      mice was observed, suggesting a significant role for complement in certain host
      defense mechanisms against B. pertussis infection.

PMID- 8300233
TI  - The Mycobacterium bovis 32-kilodalton protein antigen induces human cytotoxic T
      cell responses.
AB  - The 30-kDa protein (P32) is a mycobacterial secreted antigen which is homologous
      in Mycobacterium bovis and M. tuberculosis. In vitro, P32 induced T-cell
      proliferation. M. tuberculosis- or P32-stimulated T-cell lines lysed macrophages
      pulsed with P32 or M. tuberculosis, respectively. We conclude that P32 stimulates
      cytotoxic T cells specifically.

PMID- 8300234
TI  - Legionella pneumophila growth restriction and cytokine production by murine
      macrophages activated by a novel Pseudomonas lipid A.
AB  - Peritoneal exudate macrophages from A/J mice activated by purified lipid A
      preparations from Pseudomonas vesicularis, which contain 2,3-diamino-2,3-dideoxy
      D-glucose disaccharide phosphomonoester as the lipid A backbone, restricted the
      growth of Legionella pneumophila, an intracellular opportunistic bacteria which
      readily grows in otherwise permissive macrophages from susceptible A/J mice and
      induced production of the proinflammatory cytokines interleukin 1 and tumor
      necrosis factor alpha. Activation of the macrophages was similar to that which
      occurred after stimulation with more conventional lipid A from other bacteria
      such as salmonellae. A purified fraction A3 preparation from the Pseudomonas
      lipid A, which lacked only 1 mol of amide-linked fatty acid, in comparison with
      another fraction (A2), which contained the fatty acid, also markedly activated
      the usually permissive macrophages from susceptible A/J mice to resist growth of
      the legionellae. The fraction A3 also induced both interleukin and tumor necrosis
      factor alpha. These results show that this novel lipid A from P. vesicularis can
      activate macrophages to resist infection with an opportunistic bacterium in a
      manner similar to that induced by conventional enterobacterial lipid A and that
      the hydrophobic portion of this Pseudomonas molecule may have an important role
      in activation of macrophages.

PMID- 8300235
TI  - Immunization against experimental coccidiosis produces contrasting results in
      inbred mice of differing susceptibility to infection.
AB  - Pretreatment of inbred mice with intravenous and/or intraperitoneal injection of
      an antigen prepared from sporozoites of Eimeria vermiformis modulated the course
      of infection with the parasite in a manner that depended on the resistance
      susceptibility phenotype of the host. Mice with a resistant background (BALB)
      produced more oocysts and those with a susceptible background (C57BL) produced
      fewer oocysts than their respective controls. The optimum conditions for
      producing these effects were established, and evidence is presented which
      suggests that the phenomenon might also apply in the target host, the chicken.

PMID- 8300236
TI  - Evidence for the presence of a high-affinity laminin receptor-like molecule on
      the surface of Candida albicans yeast cells.
AB  - Two polypeptides of 37 and 67 kDa that bind laminin were detected in cell wall
      extracts of Candida albicans blastoconidia. The 37-kDa species, found only in
      yeast cell wall extracts, cross-reacted with a rabbit polyclonal antibody (PAb
      4160) directed towards the carboxyl-terminal laminin-binding domain present in
      the human 67-kDa high-affinity laminin receptor (67LR) and its 37-kDa precursor
      (37LRP), whereas another antibody (PAb 4056), directed against internal domains
      of 67LR and 37LRP, recognized a 37-kDa species in wall extracts from both
      blastoconidia and germinated blastoconidia. Indirect immunofluorescence with PAb
      4160 showed a patchy binding pattern only on yeast cells that represented about
      10% of the entire blastoconidia population.

PMID- 8300237
TI  - Conconavalin A-stimulated bovine T-cell supernatants inhibit growth of Cowdria
      ruminantium in bovine endothelial cells in vitro.
AB  - Conconavalin A-stimulated bovine T-cell supernatants inhibited the growth of
      Cowdria ruminantium in bovine endothelial cells in vitro but did not affect their
      entry. This finding represents one mechanism by which T cells may control C.
      ruminantium multiplication and hence affect the severity of disease.

PMID- 8300238
TI  - Further molecular characterization of the cloned Legionella pneumophila zinc
      metalloprotease.
AB  - On the basis of DNA sequence similarities to other Zn metalloproteases, further
      studies of the synthesis, processing, and enzymatic structure of the cloned
      Legionella protease gene, proA, were initiated. TnphoA fusions indicated that the
      entire proA open reading frame was transcribed and translated, including the 5'
      leader sequence. The results also suggested that the entire polypeptide was
      exported to the periplasm before cleavage to produce the mature protease. A site
      directed mutation in the putative active site, changing glutamate 378 to
      asparagine, abolished proteolytic activity and cytotoxicity.

PMID- 8300239
TI  - Characterization of the trehalose 6,6'-dimycolate surface monolayer by scanning
      tunneling microscopy.
AB  - The toxicity of trehalose 6,6'-dimycolate (TDM), a glycolipid of mycobacteria,
      requires presentation as a surface monolayer. Our model of the structure of the
      TDM monolayer was confirmed and extended by scanning tunneling microscopy. It
      consists of linear arrays with a periodicity of approximately 90 A (9 nm) that
      clustered in groups of four to form secondary structures with a periodicity of
      360 A (36 nm).

PMID- 8300240
TI  - Amino acids in pneumolysin important for hemolytic activity identified by random
      mutagenesis.
AB  - The structural gene of pneumolysin was randomly mutagenized. A screen, developed
      to identify mutants with reduced hemolytic activity, identified substitutions
      within the cysteine-containing region and also at residues toward the N terminus
      of the toxin. These are the first reported changes within the N-terminal region
      of the toxin that affect cytolytic activity.

PMID- 8300241
TI  - Role of iron, capsule, and toxins in the pathogenicity of Vibrio vulnificus
      biotype 2 for mice.
AB  - The virulence mechanisms of Vibrio vulnificus biotype 2 have been studied and
      compared with those of biotype 1 in mice as the experimental animals. Biotype 2
      isolates from European eels were as virulent for mice as biotype 1 strains (50%
      lethal dose, about 10(5) CFU per mouse); a septicemic infection developed in less
      than 24 h. These strains had several properties in common with biotype 1
      organisms including capsule expression, uptake of various iron sources, and
      production of exoproteins, whose role in mouse virulence has been demonstrated.
      We also discuss the implication of biotype 2 strains in human infections.

PMID- 8300242
TI  - Human secretory immunoglobulin A anti-Entamoeba histolytica antibodies inhibit
      adherence of amebae to MDCK cells.
AB  - The presence of secretory immunoglobulin A (IgA) anti-Entamoeba histolytica
      antibodies in the saliva of patients with intestinal amebiasis was demonstrated
      by immunoblot assay, and the capacity of these antibodies to inhibit amebic
      adherence to a monolayer of MDCK cells was analyzed. Inhibition was due to IgA
      antiamebic antibodies and in part to anti-Gal-binding-lectin antibodies, as
      demonstrated by absorption experiments with total amebic extract and with the
      fraction of Gal-binding lectin. These results emphasize the relevance of
      secretory IgA antibodies in the phenomenon of E. histolytica adherence to
      epithelial cells.

PMID- 8300244
TI  - Diagnostic value of bronchoalveolar lavage in patients with opportunistic and
      nonopportunistic bacterial pneumonia.
AB  - In 29 patients with community-acquired pneumonia, 24 patients with hospital
      acquired pneumonia and 35 patients with pneumonia in the immunocompromised host
      the diagnostic value of bronchoalveolar lavage (BAL) with quantitative bacterial
      and fungal cultures was studied; 32 patients with noninfectious pulmonary
      diseases and 14 healthy volunteers served as controls. An infectious etiology
      could be established in 81% of the pneumonia patients without differences between
      the three groups; significant infection was associated with colony counts of > or
      = 10(4) cfu/ml. Prior antibiotic therapy lowered the yield of BAL culture only in
      community-acquired pneumonia (94% vs 55% positive cultures in untreated vs
      pretreated patients, p < 0.02). Furthermore the culture results were related to
      the radiographic extension of pulmonary infiltrates (92% positive cultures in
      multilobar vs 54% in lobar or segmental infiltrates, p < 0.001). Therapeutic
      consequences of BAL were shown by resistance of the isolated organisms to
      predefined empiric treatment regimens in 41% community-acquired pneumonia, 43%
      pneumonia in the immunocompromised host and 67% hospital-acquired pneumonia
      patients.

PMID- 8300243
TI  - The systemic inflammatory response syndrome (SIRS): immunology and potential
      immunotherapy.
AB  - Despite widespread advances in intensive care practices, and more potent and
      effective antimicrobials, septic shock continues to have a mortality rate of
      greater than 40%. Although antimicrobials can treat the etiologic organism, they
      do not alter the host response. It is becoming clear that invading organisms and
      other insults induce the release of cytokines and secondary mediators by the
      host. These mediators produce alterations in cellular, metabolic and physiologic
      functions producing the clinical picture of septic shock. Recent advances in
      cellular and molecular biology have permitted the identification of some of the
      mediators involved in this inflammatory cascade. Potential therapies are being
      developed which block or interrupt their activity. Treatment populations must be
      meticulously defined if we are to extract useful information concerning the
      efficacy of these new treatment modalities. In the following, proposed
      definitions for clinical patterns seen in patients with sepsis, and their
      inherent problems when applied to pediatrics are discussed. The pathophysiology
      of sepsis is discussed, and specific therapies designed to interrupt the
      inflammatory cascade are examined.

PMID- 8300245
TI  - Specific IgG2 antibodies to Pseudomonas aeruginosa lipid A and lipopolysaccharide
      are early markers of chronic infection in patients with cystic fibrosis.
AB  - The IgG subclass antibody response to the two parts of Pseudomonas aeruginosa
      lipopolysaccharide; endotoxic lipid A and the O-polysaccharide, were investigated
      in a retrospective longitudinal study involving 16 patients with cystic fibrosis
      and chronic P. aeruginosa lung infection. The purpose of the study was to see if
      any of the IgG subclasses of either specificity could be used as prognostic
      markers in the development and subsequent course of the lung disease. IgG2 anti
      lipid A, IgG3 anti-lipid A, and IgG2 anti-polysaccharide showed a significant
      positive correlation with deteriorating pulmonary function already before chronic
      P. aeruginosa lung infection was diagnosed as well as in subsequent years. The
      findings suggest antigenic exposure of the patient before chronic infection is
      detected by routine sputum examinations, and further support our previous
      findings of a critical role of the IgG subclass response in modulating the course
      of inflammatory lung damage in these patients.

PMID- 8300247
TI  - Ochrobactrum anthropi bacteremia: report of four cases and short review.
AB  - Ochrobactrum anthropi, formerly "Achromobacter" CDC group Vd, is a
      nonfermentative, nonfastidious gram-negative bacillus, that only recently has
      been given attention as a potential human pathogen. Over a 2-year period, we
      observed four patients with multiple blood cultures that were positive for the
      organism. The patients had acute leukemia as underlying disease, and presented
      with clinical and microbiologic features consistent with catheter-related
      bacteremia. In three of the patients the infection initially appeared to be
      unrelated to chemotherapy-associated profound neutropenia and occurred early
      after, or was the reason for, hospital admission. The antimicrobial
      susceptibility of the isolates varied: unlike previously reported cases,
      resistance in some of our isolates included aminoglycosides, newer
      fluoroquinolones, and trimethoprim-sulfamethoxazole. Despite in vitro
      susceptibility to imipenem in initial isolates, treatment of two patients with
      this agent obviously failed to eradicate the organism, and the patients either
      relapsed with bacteremia shortly after discontinuation of treatment or remained
      persistently febrile and bacteremic. O. anthropi appears to be increasingly
      recognized as a human opportunist pathogen associated with intravascular
      catheters and unpredictable multiple antibiotic resistance.

PMID- 8300246
TI  - Plasma fibronectin concentrations in patients with HIV infection and visceral
      leishmaniasis.
AB  - Concentrations of circulating fibronectin were studied in plasma of 22 patients
      with acquired immunodeficiency syndrome and 24 healthy blood donors. There were
      significant differences between the plasma fibronectin values of the patient
      population with AIDS (mean 2 SD = 206 +/- 86 mg/l) and of the control group (mean
      +/- 2 SD = 297 +/- 92 mg/l). AIDS patients with visceral leishmaniasis showed a
      significant diminution of plasma fibronectin concentration (mean +/- 2 SD = 132
      +/- 31 mg/l). A significant increase in plasma fibronectin concentrations was
      noted after 14 days of treatment with antimony (mean 2 SD = 239 +/- 67 mg/l).
      These results suggest that the measurement of fibronectin concentrations in
      patients with AIDS especially with concurrent infection, contributes to
      diagnosis. A significant decrease in plasma fibronectin concentrations was
      observed in patients with AIDS and visceral leishmaniasis.

PMID- 8300248
TI  - The effect of FCE 22891, a new oral penem, on faecal flora anaerobes and their
      fermentation end products in patients with chronic obstructive pulmonary disease.
AB  - The influence of FCE 22891 on the faecal flora was investigated in 11 patients
      with an acute exacerbation of chronic obstructive pulmonary disease (COPD).
      Colony counts of faecal (an)aerobes and concentrations of their short-chain fatty
      acids and organic acids were determined simultaneously in fresh faeces before,
      during and after administration of the drug, and compared to those of healthy
      human volunteers. The MIC of FCE 22891 for the 142 isolated anaerobes was
      determined, and compared to the biologically active concentration of the drug in
      faeces. The Bacteroides colony counts of the patients increased significantly by
      day 9 compared to day 3, but were significantly lower than those of the healthy
      controls before, during and after the study. Significant changes in short-chain
      fatty acids and organic acid concentrations occurred in faeces of the patients
      during and after treatment, and especially when compared to healthy controls. A
      strong increase in MICs during treatment was found in Clostridium species, other
      than Clostridium difficile. FCE 22891 had only a moderate effect on the
      composition of the anaerobic faecal flora, but bacterial fermentation was mainly
      disturbed before and early on in treatment, which could have been caused by the
      disease.

PMID- 8300249
TI  - Isolation of Chlamydia trachomatis from the lower digestive tract.
AB  - Chlamydia trachomatis was isolated from ten of 188 biopsies (5.3%) obtained from
      different parts of the lower digestive tract. Patients (mean age 37.0 years)
      presented with ulcerative proctitis, Crohn's disease, mild colitis or ulcerative
      colitis. Seven rectal biopsies, two biopsies from the sigmoid flexure and one
      caecal biopsy were positive for chlamydial isolation whereas all biopsies taken
      from the colon ascendens, transversum or descendens and from the terminal ileum
      were negative. We conclude that isolation of C. trachomatis is most effective
      from rectal and sigmoidal biopsies and is a rare event from other sites of the
      lower digestive tract.

PMID- 8300250
TI  - In vivo potentiation of polymorphonuclear leukocyte chemotaxis by clindamycin.
AB  - Polymorphonuclear leukocyte (PMNL) chemotaxis was evaluated in ten healthy
      volunteers who had received 600 mg of clindamycin intramuscularly. Serum obtained
      3 hours after the administration of clindamycin significantly increased PMNL
      chemotaxis. Serum obtained at 12 and 24 hours after the administration of the
      drug did not induce significant increase in PMNL chemotaxis. The administration
      of clindamycin had no direct effect on the PMNLs in terms of their chemotactic
      activity. These results demonstrate serum-associated augmentation of PMNL
      chemotaxis by clindamycin in vivo which may be of potential clinical benefit in
      the outcome of infections.

PMID- 8300251
TI  - Short course intermittent chemotherapy in childhood tuberculosis.
AB  - A total of 130 children diagnosed as having pulmonary and extrapulmonary
      tuberculosis who received short course intermittent chemotherapy between 1978
      1992 were evaluated retrospectively. One hundred and ten children with
      tuberculosis were treated with isoniazid (10-15 mg/kg, maximum 400 mg), rifampin
      (10-15 mg/kg, maximum 600 mg), and streptomycin (30 mg/kg, maximum 1 g) daily,
      for 15 days. Treatment was completed with similar doses of isoniazid and rifampin
      twice a week for a period of 9 months. Since 1986, 20 children with tuberculosis
      were being treated with the same regimen but without streptomycin. The majority
      of patients in these cases had pulmonary tuberculosis (75%), followed by lymph
      nodes (9%), pleural (7%), bone and joint (5%), miliary (3%), and abdominal
      tuberculosis (1%). The clinicoradiologic response to treatment was observed to be
      excellent. Only one case of relapse was detected, which was the case of a patient
      with lymph node tuberculosis that occurred 18 months after the completion of
      treatment. No serious adverse drug reaction was observed in any of the cases
      mentioned. In conclusion, short-course low-dose intermittent chemotherapy is an
      effective and economical treatment with minimal side effects for pulmonary and
      extrapulmonary tuberculosis in childhood.

PMID- 8300252
TI  - NotI macrorestriction analysis suggests a clonal relationship of Salmonella
      enterica, ser. enteritidis phage lysotype 4 strains.
AB  - 30 different strains of Salmonella enterica ser. enteritidis (S. enteritidis)
      isolated at the Institute for Medical Microbiology, Hannover, were subjected to a
      NotI macrorestriction analysis. The results were compared with the respective
      phage lysis patterns. 25 of 30 isolates belonged to phage lysotype 4; all these
      strains displayed an identical genomic NotI restriction fragment pattern. In
      contrast, five isolates of other phage lysotypes revealed more or less prominent
      differences in their NotI restriction fragment pattern. These results provide
      genetic evidence for a clonal expansion of a single phage lysotype 4 strain
      underlying the recent surge in salmonella infections and support phage lysotyping
      as a reliable epidemiological typing method for S. enteritidis.

PMID- 8300253
TI  - Septic abortion associated with Campylobacter fetus subspecies fetus infection:
      case report and review of the literature.
AB  - In contrast to the situation in cattle, goat and sheep, Campylobacter fetus
      subspecies fetus only rarely causes disease in humans. While a major inducer of
      septic abortion in animals, only a minority of clinical infections in humans are
      found during pregnancy. Eleven cases have so far been described in pregnant
      women. Clinical symptomatology is usually mild during gestation but often leads
      to premature labor. Here we present a multigravida with positive cultures for C.
      fetus who went into septic shock. She completely recovered after delivery of a C.
      fetus-infected fetus at 18 weeks' gestation and treatment with a combination of
      cephazolin and gentamicin. C. fetus infections should be suspected in patients
      with intensive contact with (infected) cattle or after intake of unpasteurized
      dairy products.

PMID- 8300254
TI  - Tuberculous pericarditis as the first manifestation of AIDS.
AB  - Although it is known that extrapulmonary tuberculosis in patients with AIDS has a
      broad spectrum of clinical manifestations, pericardial involvement has rarely
      been described. We report a case of this condition as the first manifestation of
      AIDS with good response to antituberculous therapy. Although unusual, the
      diagnosis of tuberculous pericarditis in symptomatic HIV-infected patients should
      be aggressively pursued because of the beneficial clinical response to treatment.

PMID- 8300255
TI  - Panaritium ossale et articulare caused by Moraxella nonliquefaciens.
AB  - Only little is known about soft tissue, bone or joint infections caused by
      Moraxella spp. A case of panaritium ossale et articulare caused by Moraxella
      nonliquefaciens in an 80-year-old patient immunocompromised by diabetes mellitus
      and liver insufficiency is reported here. Surgery, local antiseptic treatment,
      and therapy with aminopenicillins plus beta-lactamase-inhibitors led to complete
      cure of the infection within 10 days.

PMID- 8300256
TI  - A fatal case of Yersinia enterocolitica septicemia associated with mycotic aortic
      aneurysm.

PMID- 8300257
TI  - Root canal morphology of maxillary permanent first molar teeth at various ages.
AB  - The root canal anatomy and pulp chamber morphology of 216 maxillary permanent
      first molar teeth of known age was examined using a radiographic technique after
      infusion of the root canal system with a radiopaque sodium iothalomate gel. This
      technique proved to be a rapid and effective method for the examination of root
      canal morphology and is recommended when root canal anatomy needs to be examined
      before further investigations are carried out. Over 95% of palatal and disto
      buccal roots contained a single root canal. The mesio-buccal root was more
      complex. All types of configurations were seen. Only 26% of mesio-buccal roots
      showed a single canal. The pulp canal in all roots appeared to narrow at an early
      age. In the mesio-buccal root, a definite two-directional calcification pattern
      was apparent in most teeth by the age of 10. The rate of progress of root
      formation was very variable. There was no apparent relationship between the type
      of canal system in the mesio-buccal root and the type of canal orifice present.
      The transverse cross-sectional shape of the pulp chamber was trapezoidal in 81%
      of teeth.

PMID- 8300258
TI  - The use of E-speed film for root canal length determination.
AB  - This study compared the use of D-speed and E-speed dental X-ray film for
      assessing the working length of root canals. Root canal files of varying size
      (ISO 06, 08, 10 and 15) were placed in the root canals of a maxillary molar and a
      mandibular molar in a dried skull and mandible. Files were set at various lengths
      relative to the radiographic apex. The X-ray projections were kept constant.
      Exposure settings for the two film types that gave comparable radiographic
      density were selected. Films were developed manually under standardized
      conditions. A total of 48 films of each type were examined at various
      magnifications by four trained examiners for the estimation of distance between
      the file tip and radiographic apex. There were no differences between examiners
      in estimating working length. The effect of file size, root and magnification
      were also not significant. The differences between the film types were not
      significant (P > 0.05). It is concluded that clinicians should use E-speed film
      instead of D-speed film for root canal length measurement, because the exposure
      time was reduced by over 40% but the quality of the radiographic image was not
      significantly different.

PMID- 8300259
TI  - Management of the resected root end: a clinical review.
AB  - Careful management of the resected root end during endodontic surgery is critical
      to the overall success of the case. After resection, the root structure presents
      with multiple anatomical variations and considerations at both a macroscopic and
      microscopic level. These include root outline, canal anatomy, dentinal tubule
      configuration, presence of a smear layer and root canal filling material. Proper
      assessment of these variables will dictate the best methods for root-end
      management, along with the attainment of an anatomically compatible root face for
      optimal healing of the periradicular tissues.

PMID- 8300260
TI  - Temperature and surface changes of dentine and cementum induced by CO2 laser
      exposure.
AB  - The thermal effects of a CO2 laser on the external root surface and inside the
      root canal were studied in vitro by means of computerized infrared (IR)
      thermography and a digital thermometer. One-hundred-and-eighty tooth roots with
      single root canals were irradiated internally and externally with laser power set
      at 0.5, 1, 1.5, 2, 3 and 4 W. The laser was used in two operating modes: pulsed
      (pulse 0.5 s) and continuous mode with exposure time of 10 s. Under the
      conditions of this experiment, temperature rises of between 1.5 and 19.1 degrees
      C at the external root surface and 1.5 and 12 degrees C inside the root canal and
      horizontally across the sectioned root surface were recorded. The results
      obtained with IR camera showed a higher temperature on the external root surface
      than the digital thermometer during and after lasing the root canal. Scanning
      electron microscope (SEM) analysis revealed that even low laser energy
      significantly damaged the external root cementum surfaces.

PMID- 8300261
TI  - Failure behaviour of fatigue-tested post and cores.
AB  - Evaluation of the long-term behaviour of restorations in clinical trials can be
      time-consuming. A partial alternative to the clinical trial can be found in
      mechanical fatigue testing. The aim of this study was to evaluate the failure
      behaviour of post and core restored teeth when subjected to cyclic mechanical
      loading and to compare it with quasistatic failure. Eighty seven premolar teeth
      were restored with a titanium alloy post and an amalgam or composite core. Five
      to 21 days after restoration, the specimens were subjected to cyclic loading
      (frequency 5 Hz), at an angle of 45 degrees to the long axis of the tooth. The
      load levels were 50, 60, 65 and 70% of mean quasistatic failure loads. The
      specimens were divided into three groups according to their survival time: short
      (S) (< 10(4) cycles), intermediate (I) (10(4) < or = life < 10(5) cycles) and
      long (L) (> or = 10(5) cycles). For both core materials failure behaviour changed
      after approximately 10(5) cycles, and the change was most marked for the
      composite group. Catastrophic fatigue failure consisted of core fracture in the
      amalgam group (three times) and of post fracture in the composite L group (four
      times). Three post fractures occurred at a site theoretically predisposed to
      fatigue failure. It was concluded that fatigue failure characteristics of post
      and core restorations may be very different from those of quasistatic failure.
      Therefore, in addition to quasistatic tests, fatigue tests are necessary,
      covering at least 10(5) load cycles.

PMID- 8300262
TI  - The penetration of root canal sealers into dentinal tubules. A scanning electron
      microscopic study.
AB  - The purpose of this study was to evaluate the effect of smear layer on
      penetration of four root sealers into dentinal tubules. Sixty-four, recently
      extracted, human maxillary and mandibular incisors were used. Following removal
      of the crowns, the pulps were extirpated and the root canals instrumented. The
      teeth were then divided into two groups. The teeth in the control group were
      irrigated with saline solution and the experimental group treated with EDTA and
      NaOCl. Each main group was then divided into four sub-groups and the root canals
      filled with Diaket, N2 Universal, SPAD and Forfenan as recommended by the
      manufacturers. The teeth were split longitudinally and examined using scanning
      electron microscopy. A quantitative assessment was made of sealer penetration
      into the dentinal tubules in the coronal, middle and apical parts of each root
      canal. It was observed that the smear layer obstructed the penetration of the
      tubules by the sealers. However, in the experimental group, the penetration into
      dentinal tubules was better with Diaket, N2 and SPAD, than with Forfenan (P <
      0.01). It was concluded that this penetration could be affected by physical and
      chemical properties of root canal filling materials.

PMID- 8300263
TI  - Calcium hydroxide paste in the maxillary sinus: a case report.
AB  - A case is reported in which a perforation of the sinus floor of the maxillary
      sinus occurred with extrusion of a calcium hydroxide paste during routine root
      canal treatment of a maxillary premolar. All clinical manifestations are
      described as well as the results of a follow-up evaluation.

PMID- 8300264
TI  - Transcutaneous pCO2-monitoring for the evaluation of the anaerobic threshold.
      Comparison to lactate and ventilatory thresholds.
AB  - The monitoring of transcutaneous pCO2 (pCO2(tc) is an alternative to the invasive
      determination of the anaerobic threshold by analysis of arterial lactate
      concentration or to the uncomfortable determination of the ventilatory threshold.
      We compared the threshold determination by pCO2(tc)-monitoring to the 4 mmol/l
      lactate threshold and to the ventilatory threshold (point where the ventilatory
      equivalent of oxygen started to increase continuously) in 15 athletes during
      cycle exercise. The first distinct deflection point in the pCO2(tc) time course
      after the start of exercise was chosen to indicate the anaerobic threshold. The
      mean threshold determined by pCO2(tc) occurred at the same workload as the
      ventilatory threshold but at a lower workload than the lactate threshold. In
      spite of the good correspondence in the respective means there was a wide range
      of individual differences between the pCO2(tc) derived thresholds and both
      reference thresholds. Thus, looking at an individual, the continuous monitoring
      of the pCO2(tc) does not provide reliable data on the occurrence of the
      transition from aerobic to anaerobic metabolism.

PMID- 8300265
TI  - Peak torque occurrence in the range of motion during isokinetic extension and
      flexion of the knee.
AB  - The purpose of this study was to 1) assess the knee angles of hamstring and
      quadriceps peak torques at slow (60 degrees.sec-1) and moderate (180 degrees.sec
      1) isokinetic velocities in healthy adult males (N = 143) and females (N = 106),
      2) determine if velocity has an effect on these peak torque angles, and 3)
      determine if subject's age, sex, and muscle strength have an effect on the
      results. The Cybex II dynamometer was used to record the measurements. At 60
      degrees.sec-1, the mean peak torque for the hamstrings occurred at 33 degrees for
      men and 37 degrees for women (p < 0.001) (0 degree = full extension). At 180
      degrees.sec-1, the corresponding angles were 40 and 44 degrees (p < 0.01). In
      both groups the increase was 7 degrees (p < 0.001). At 60 degrees.sec-1, the peak
      torque angle of the quadriceps was 54 degrees in both groups. At 180 degrees.sec
      1, the angle occurred significantly later in men (11 degrees later) and in women
      (10 degrees later) (p < 0.001 for both). Subject's age (18 to 40 years) did not
      affect the results. In female hamstrings, the knee angle of peak torque had a
      highly significant (p < 0.001) negative correlation to muscle strength; that is,
      in female hamstrings, the peak torque angles occurred later in the range of
      motion when muscle strength decreased. This possibly explained the difference
      observed between men and women in the peak torque angles of hamstrings. In
      conclusion, people involved in isokinetic testing of muscular performance should
      be aware that the peak torque occurs later in the range of motion with increasing
      angular velocity, especially when testing weak muscle groups. In high angular
      velocities this may become a problem since the limb may pass the optimal joint
      position for muscular performance, and the recorded peak torque may not represent
      the subject's maximal torque capacity.

PMID- 8300266
TI  - Brainstem auditory evoked potentials. Differences related to physical activity.
AB  - Shorter sensory-motor reaction times have been reported in athletes compared with
      sedentary subjects. Previous results have shown significantly shorter visual
      evoked potentials (VEPs) latencies in a group of tennis players, but there was no
      difference between a group of rowers and control subjects. In the present study,
      the same groups were investigated in order to establish whether similar
      differences could be found in relation to brainstem auditory evoked potentials
      (BAEPs). Waves I to V latencies (Ls), interpeak latencies (IPLs) and wave
      amplitudes were measured. The results showed great differences related to gender.
      The I-III IPL was shorter in the females than in the males. Differences were also
      found in relation to physical activity. The most important feature was the
      significantly shorter III-V IPL observed in the rowers and in the tennis players
      of both genders compared with sedentary control subjects. In the males these
      differences were linked to training factors. Therefore, unlike VEPs which seemed
      to be linked to sports requiring high visual acuity, BAEPs seemed to be linked
      more widely to top-class physical activity and not to specific sensory aptitude.
      It was hypothesized that the shorter III-V IPL might be due to shorter synaptic
      transmission time in the superior olivary complex.

PMID- 8300267
TI  - The bronchoconstrictor effect of strenuous exercise at low temperatures in normal
      athletes.
AB  - In competitive speed skating healthy athletes complain of subjective variants of
      exercise-induced bronchoconstriction such as coughing, chest tightness and
      excessive mucus production. This is especially so after a 1500 m race which can
      be considered as extremely strenuous. We compared peak expiratory flow (PEF)
      measurements 3, 10, 20, 60, 90 and 120 min after such a race with baseline, just
      before the race, in 10 adults in a competitive situation in Calgary (Canada) and
      The Hague (NL) and in 8 children in Utrecht (NL). A gradual decline in PEF was
      found, the mean decrease reaching significance (p < 0.05) at 10, 90 and 120 min
      in Calgary, at 90 and 120 min in The Hague and at 90 min in Utrecht for the
      children. The mean decrease over the whole period was significantly greater
      (3.6%, SEM 0.6%) in Calgary when compared with The Hague. The decrease could not
      be explained by the daily PEF variation that we measured in both groups. We
      conclude that there is a slight bronchoconstrictory effect, even in healthy
      athletes, when partaking in this strenuous type of exercise at low temperatures.
      An explanation may be the strong drying and temperature stimulus to the airways,
      stimulating vagal nerve activity, causing not only the cough and mucus production
      but also a gradually increasing minor bronchoconstriction.

PMID- 8300268
TI  - The possible role of intracellular Ca2+ accumulation for the development of
      immobilization atrophy.
AB  - Little is known about the cellular mechanisms which induce the development of
      skeletal muscle immobilization atrophy. Initial disturbances in cellular
      homeostasis seem to occur very early during immobilization. The aim of the study
      was to investigate whether loss of calcium homeostasis might be of etiological
      importance for atrophy. Therefore a calcium channel blocker (nifedipine) was
      administered to mice immobilized for four days, and their soleus muscle was
      investigated comparatively to immobilized animals without nifedipine. The
      immobilized muscles showed an atrophy of about 15% which was not the case in
      nifedipine-treated immobilized muscles. Ultrastructural alterations (lysosomes,
      mitochondrial damage) were found predominantly in the immobilized muscles, but
      rarely with nifedipine. It was concluded that nifedipine protected the muscle
      fibers probably against calcium overload, thereby avoiding an autophagic response
      and an impairment of mitochondrial respiratory function.

PMID- 8300269
TI  - Endothelium-derived oxidative stress may contribute to exercise-induced muscle
      damage.
AB  - In exercise-induced muscle damage, oxidative stress derived from the liberation
      of reactive oxygen species (ROS) is assumed to be of etiological importance.
      Xanthine oxidase (XO) located in capillary endothelium is one of the possible
      sources for ROS, mainly investigated so far under conditions of
      ischemia/reperfusion. XO can be inhibited by allopurinol. To investigate the
      contribution of XO for the oxidative stress-induced development of muscle damage,
      mice were subjected to a single bout of exhaustive running exercise. Another
      exercised group received allopurinol. The reduced form of glutathione (GSH) was
      measured to estimate the amount of oxidative stress in soleus muscle, and the
      same muscle was examined in the light and electron microscope at different
      periods of time (0, 48, 96 h) after exercise. While exercise alone resulted in a
      marked reduction of GSH indicative for oxidative stress, which only recovered at
      96 h, the administration of allopurinal to exercised animals induced a complete
      recovery already at 48 h after exercise. Muscle damage was more pronounced in the
      exercised animals which had not been treated with allopurinol. It is concluded
      that endothelium-derived ROS contribute reasonably to oxidative stress to
      exercised muscle and to fiber and capillary damage.

PMID- 8300270
TI  - Bioenergetic characteristics in prepubertal swimmers. Comparison with active and
      non-active boys.
AB  - The effects of physical activity (PA) on bioenergetic characteristics were
      studied in 53 prepubertal boys. Maximal oxygen consumption (VO2max; direct
      method), maximal anaerobic power (Pmax, force-velocity test), and mean power in
      30 s (P30s, Wingate test) were compared (mean +/- SD) in three groups of boys of
      the same age (11 years): swimmers (Sw, n = 26, PA = 8 +/- 3 hrs/week), active
      boys (A, n = 16, PA = 7 +/- 2 hrs/week) and non-active boys (C, n = 11, PA = 3 +/
      2 hrs/week). No significant difference appeared between groups for VO2max (Sw,
      50.7 +/- 5.4; A, 50.8 +/- 6.0; C, 49.4 +/- 7.0; ml.min-1 x kg-1), Pmax (Sw, 8.1
      +/- 1.4; A, 8.4 +/- 1.4; C, 8.1 +/- 1.4; W.kg-1) and P30s (SW, 5.8 +/- 1.0 A, 6.3
      +/- 1.7; C, 5.0 +/- 1.1; W.kg-1). Significant relationships (p < 0.01) existed
      between Pmax, P30s (W.kg-1) and VO2max (ml.min-1 x kg-1): r = 0.37 and r = 0.40,
      respectively. This indicates that there is neither aerobic nor anaerobic
      specialization during prepubertal development, and that regular sporting activity
      induces no great changes in the bioenergetic characteristics of prepubertal boys.

PMID- 8300271
TI  - Changes in rowing ergometer, weight lifting, vertical jump and isokinetic
      performance in response to standard and standard plus plyometric training
      programs.
AB  - The purpose of this study was to compare standard (S-weight plus rowing ergometer
      training) and standard plus plyometric (S+P-weight plus rowing ergometer
      training, plus plyometric exercises) programs on sport-specific and non sport
      specific tests. Twenty-four female rowers completed the weight training or the
      weight training plus plyometric exercises three times per week and rowing
      ergometer training four times per week, 1 hr per session for 9 wks. Analysis of
      variance tests were used to compare S (n = 11; 5 novice and 6 experienced rowers)
      and S+P (n = 13; 7 novice and 6 experienced rowers) programs on the following
      sport-specific tests: 1) time to row 2,500 m and 2) distance rowed in 90 s; and
      on the following non sport-specific tests: 1) leg press, 1 RM, 2) leg press
      endurance, 3) bench pull 1 RM, 4) bench pull endurance, 5) vertical jump, 6-9)
      isokinetic knee extensor peak and average power during concentric and eccentric
      muscle actions and 10) angle of occurrence of peak torque during concentric
      muscle actions (isokinetic knee extension). Although experienced oarswomen scored
      significantly higher than did novice oarswomen on eight of 12 tests (p < 0.04),
      both levels of rower responded similarly to training. No significant differences
      were observed post-training between the S and S+P training programs (p > 0.05).
      These results do not discount the value of plyometric exercises, but indicate
      that the jump exercises used offered no advantages to intercollegiate oarswomen.

PMID- 8300272
TI  - Physiological characteristics of elite and club level female triathletes during
      running.
AB  - Most studies of the triathlon have looked at male triathletes with respect to the
      longer distance events such as the Hawaii Ironman Triathlon. The purpose of this
      study was to investigate and compare the physiological characteristics and
      training protocols of elite and competitive (club) women triathletes who compete
      at Olympic distance (1.5 km swim, 40 km cycle, 10 km run) to examine the
      relationship between these factors and running performance in the triathlon. The
      elite triathletes (n = 10) had a lower body mass and BMI than club level
      triathletes (n = 9) as well as smaller girths at all measured sites although
      these differences were not significant. Sum of skinfold thickness measured at
      four sites was significantly smaller in the elite group (p = 0.05), yet, wide
      individual variations were found within each group. The amount of training
      undertaken by individuals in both groups varied markedly; however, overall the
      elite did more training in all disciplines. The VO2max measured on the treadmill
      was significantly higher (p = 0.03) in the elite women (65.6 +/- 6.0 ml.kg-1.min
      1) as compared to the club level women (60.4 +/- 3.1 ml.kg-1.min-1). The elite
      triathletes were significantly more economical, showing a lowered relative oxygen
      consumption (% VO2max), (p = 0.008); lowered heart rate (p = 0.01) and lowered
      blood lactate values (p = 0.03) at 15 km.h-1. The elite group were also much more
      efficient runners at 15 km.h-1 when looking at VE/VO2 (p = 0.05). An association
      was found between run race time and %VO2max at 15 km.h-1 (p = 0.04). The results
      suggest that there is no ideal nor unique anthropometric profile that can be
      established for female triathletes especially with respect to running time and
      overall performance. The widespread differences in physiological variables found
      between the two groups confirms the important contribution factors such as these
      make to performance.

PMID- 8300273
TI  - A short cycle ergometer test to predict maximal workload and maximal oxygen
      uptake.
AB  - In order to develop a short cycle ergometer test for the prediction of maximal
      oxygen uptake (VO2max) and maximal work load (Wmax) oxygen uptake, workload and
      heart rate data were collected in 22 subjects. In the first test the subjects
      cycled at two submaximal stages of 3 min each whereafter the workload was quickly
      (within 4 min) increased to a supramaximal level to attain the maximal heart
      rate. A second graded cycle test was used to compare observed Wmax and VO2max
      with estimated Wmax and VO2max. The means of the estimated Wmax and observed Wmax
      were 364.9 (SD +/- 42.4) watts and 368.8 (SD +/- 40.2) watts, respectively and
      the mean estimation error was -1.0% (range -7.1% to 4.4%). For 82% of the
      subjects the estimation error was within +/- 5%. The means of the estimated
      VO2max and observed VO2max were 4.49 (SD +/- 0.45) l.min-1 and 4.59 (SD +/- 0.41)
      l.min-1, respectively. The mean estimation error was -2.1% (range -13.8% to
      5.1%). For 68% of the subjects the estimation error was within +/- 5%. It is
      concluded that for trained athletes the short test (8-10 min) is accurate for the
      estimation of Wmax and VO2max by measuring two submaximal heart rates and maximal
      heart rate and making use of the linear relationship between heart rate, workload
      and oxygen uptake.

PMID- 8300274
TI  - Brief physical inactivity prolongs colonic transit time in elderly active men.
AB  - The effects of two weeks of reduced activity on gastrointestinal transit time
      were studied in nine healthy elderly subjects, who had engaged in regular
      recreational exercise for ten years. Physical inactivity was achieved by a
      restriction of all kinds of physical exercise and by staying at home. Mouth-to
      cecum transit time was measured by a breath hydrogen method and mean total and
      segmental colonic transit times by a radiopaque marker method. The mouth-to-cecum
      transit time did not change during the period of physical inactivity. The mean
      total colonic transit time (10.9 +/- 2.7 h) was significantly prolonged to 19.5
      +/- 2.9 hours during the physical inactivity (p < 0.01). This prolongation was
      due to slowed transit through the right and the left segments of the colon. The
      transit time of the rectosigmoid segment of the colon was not affected. In
      conclusion, the period of physical inactivity prolonged the colonic transit time
      in active elderly subjects.

PMID- 8300275
TI  - Effect of a short maximal physical exercise on the eosinophil cationic protein.
AB  - Eosinophil cationic protein (ECP) has been shown to be a marker of eosinophil
      granulocyte activation. In 10 healthy young subjects the plasma concentrations of
      ECP were measured before and after a graded maximal bicycle exercise test. The
      analyses were carried out 30 min before and immediately before exercise,
      immediately after exercise and 20 and 45 min later. The post-exercise values were
      corrected for plasma volume changes which were calculated from hematocrit and
      hemoglobin values. Immediately post-exercise the ECP increased significantly (p <
      0.01) from 1.25 +/- 0.28 at rest to 2.40 +/- 0.59 micrograms/l. Twenty and 45 min
      later the values normalized and significant differences from the pre-exercise
      values could no longer be measured. The results provide strong evidence for an
      activation of eosinophil granulocytes after a short maximal exercise.

PMID- 8300276
TI  - Food efficiency in rats following brain lesions which affect target body size:
      implications on the set point for target size.
AB  - Target size, i.e. body size appropriate for age, may be reset by bilateral
      lesions of several brain areas. The mechanism for control of target body size is
      unknown, but some of the loci have marked effects on gustatory behavior and/or
      energy metabolism. We have tested the possibility that a disturbance in energy
      metabolism may be a common factor in resetting target size. Food efficiency for
      body weight gain and for metabolic size (the 0.75 power of body weight) was
      determined in rats that were experimentally stunted by neonatal head-irradiation
      or by bilateral electrolytic lesions produced soon after weaning in the
      dorsomedial hypothalamic nuclei (DMH) or the substantia nigra (SN). The
      irradiations were carried out in males and females; the surgical lesions were
      produced only in males. Observations were carried out from weaning through early
      adulthood. Subgroups of irradiated rats and controls were fasted for 48 hours at
      40 days of age. Irradiated rats had reduced food efficiency for weight gain and
      for metabolic size, more marked in males than in females. DMH or SN lesions did
      not change food efficiency for weight gain. Food efficiency for metabolic size
      increased after DMH lesions and declined after SN lesions. During refeeding after
      a fast, irradiated rats showed a normal transient increase in food efficiency for
      weight gain, but not for metabolic size. The differences in food efficiency
      following different lesions tend to exclude altered energy metabolism as a common
      factor in the reset of target body size.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300277
TI  - The costs of reproduction and dietary restriction: parallels between insects and
      mammals.
AB  - Dietary restriction increases life span in mammals. This essay connects the
      dietary restriction response to evolutionary life history theory and experiments
      related to it. Evolutionary biologists have shown mathematically that aging is an
      inevitable consequence of age-specific natural selection acting on species with
      somata separate from germ lines. Empirical tests of this prediction currently
      point to its general validity. Two specific genetic mechanisms are known which
      could underlie the evolution of aging under these conditions: age-specificity of
      gene effects and antagonistic pleiotropy between early and late ages. The
      antagonistic pleiotropy theory assumes that some genes with beneficial effects on
      early life fitness will have deleterious effects upon fitness in later life.
      Experimental work in insects, particularly selection experiments in Drosophila
      melanogaster, has tested these ideas. The negative genetic correlation between
      longevity and reproductive effort produced by selection has been shown to be
      paralleled, in some cases, by environmental manipulation. Thus the increase in
      life span caused by dietary restriction might be explained as an incidental
      consequence of lower reproductive effort. This response also could have been an
      adaptation that enhanced fitness in some species that faced uncertain food
      supplies, a condition that may have evolved independently in a wide variety of
      taxa. Several schools of research, besides that of the evolutionary biologists
      concerned with genetic correlations, have produced corroborations of this
      hypothesis in insects and mammals: the gerontological work on life span
      extension, reproductive physiologists concerned with factors that affect
      fertility, and various life history studies.

PMID- 8300278
TI  - Lymphocyte aging in bone marrow chimeras.
AB  - Chimeric mice provide a unique approach to the analysis of genetic factors
      associated with aging since cells with two genetically distinct backgrounds can
      be analyzed in the same animal. In this study, bone marrow chimeras were produced
      by reconstituting lethally irradiated female B6AF1 [(C57BL/6 female x A male)F1]
      mice with varying mixtures of T cell-depleted bone marrow cells from A (short
      lived) and C57BL/6 (long-lived) mice. The phenotypic composition of the
      peripheral blood lymphocytes was analyzed using either a cytotoxicity assay or
      flow cytometry with indirect immunofluorescence. The percentage of A-derived
      lymphocytes in the peripheral blood following reconstitution was generally higher
      than the percentage of A bone marrow cells with which the irradiated mice were
      inoculated, suggesting that the cells from the A donor bone marrow were more
      efficient at marrow reconstitution than the cells from the C57BL/6 donor bone
      marrow. In order to determine whether the percentage of A- versus C57BL/6-derived
      cells changed with age in each animal, the chimeric mice were bled for phenotype
      analysis of peripheral blood lymphocytes between 2-6 months following
      reconstitution and at 2-3 month intervals until death. For most animals [93/127
      (73%)], there was no consistent pattern of increase or decrease (> 20%) with
      regard to the percentage of A lymphocytes in the peripheral blood over time.
      However, in 34/127 (27%) of the chimeras, a change greater than 20% in the
      phenotypic composition of the peripheral blood lymphocytes was observed and these
      animals were considered unstable. Among these 34 unstable animals, 6 (18%) showed
      an overall increase in A-derived lymphocytes, 24 (71%) showed an overall decrease
      in A-derived lymphocytes, and 4 (12%) showed fluctuating increases and decreases
      over their lifespan. While the lifespans of the chimeric animals in these studies
      were considerably shorter than those reported for untreated mice of the same
      strain and gender, in these animals increased proportions of A cells were
      associated with significantly longer lifespans. In addition, the lifespan of the
      B6AF1 chimeric mice was a function of the proportion of A lymphocytes present in
      the peripheral blood over the course of the animal's life.

PMID- 8300279
TI  - Are somatic cells inherently deficient in methylation metabolism? A proposed
      mechanism for DNA methylation loss, senescence and aging.
AB  - A mechanism of aging is proposed for mammals and other vertebrates. In this
      mechanism, most somatic cells have inherent deficiencies in methylation
      metabolism with respect to their capacity to methylate DNA. This leads to
      incomplete DNA methylation in each cell cycle which, accumulated over many cell
      cycles, contributes to genetic instability, senescence and cancer. These proposed
      metabolic deficiencies are present from the time somatic cells are young, yet it
      is only after many cell divisions that deleterious effects are realized. In
      nature, most animals have reproduced or have been killed by predators or other
      environmental hazards before they can be greatly affected by these deficiencies.
      These deficiencies evolved in animals eating a balance of nutrients from nature.
      Evidence from the literature is reviewed which establishes that methylation is
      lost from the DNA of many mammalian somatic cells as they age both in vivo and in
      vitro, and that DNA methylation levels are influenced by factors, such as diet,
      that affect methylation metabolism. Partially correcting the proposed
      deficiencies is considered as a possible molecular mechanism by which caloric
      restriction extends lifespan. Other possible dietary and transgenic means to
      correct the proposed deficiencies and extend lifespan are discussed.

PMID- 8300281
TI  - Contributions to the phylogeny of Platyhelminthes based on partial sequencing of
      18S ribosomal DNA.
AB  - Partial sequencing of the 18S ribosomal DNA gene of one nemertean and 13 free
      living and parasitic Platyhelminthes (556 nucleotides), and of one nemertean and
      20 Platyhelminthes (556 nucleotides) was used to test several hypotheses
      concerning the phylogenetic relationships of Platyhelminthes. The following
      conclusions were reached: the Neodermata is monophyletic; Trematoda
      (Aspidogastrea and Digenea) is monophyletic, although a sister group relationship
      of the Aspidogastrea and all other Neodermata cannot be definitely ruled out; the
      Cestoda comprising the Eucestoda, Amphilinidea and Gyrocotylidea is monophyletic;
      it is unresolved whether the Monogenea is paraphyletic; neither Gyrocotylidea and
      Monopisthocotylea nor Gyrocotylidea and Monogenea as a whole are sister groups;
      Anoplodiscus is a monopisthocotylean monogenean; none of Proseriata,
      Pterastericolidae/Umagillidae, Kalyptorhynchia, Rhabdocoela as a whole,
      Dalyelliida or the Temnocephalidae is the sister group of the Neodermata; there
      is some evidence that a larger taxon consisting of Proseriata, Tricladida and
      Rhabdocoela may be the sister group of the Neodermata but definitive evidence for
      a sister group relationship between the Neodermata and any turbellarian taxon is
      lacking; Rhabdocoela and Lecithoepitheliata are not closely related; it is
      unresolved whether the Rhabdocoela is monophyletic; Umagillidae,
      Pterastericolidae and Temnocephalidae belong to one monophylum; the
      Temnocephalidae are very close to the dalyelliids; Tricladida and Rhabdocoela are
      sister groups, the exact position of the Catenulida and Nemertini in relation to
      the Platyhelminthes has not been resolved, although Catenulida and
      Lecithoepitheliata may belong to one clade.

PMID- 8300280
TI  - Origin of the avian glycogen body. II. Observations in support of a glial nature
      in the chick embryo.
AB  - Stem cells of the glycogen body in chick embryos at 7-8 days of incubation
      (stages 31-34) were studied by light microscopy autoradiography,
      immunocytochemistry, and following induced spina bifida to discern their nature
      and origin. Glycogen cells displayed the presence of glial fibrillar acid protein
      and vimentin at the time of their appearance at 7-8 days of incubation (stages 31
      34). Displayed also were indications of DNA synthesis by thymidine incorporation
      during that period of development. Observations suggest that glycogen body cells
      are glial in nature, possibly radial glia which arise from neuroepithelium that
      comprises the ependyma and roof plate of the avian lumbosacral spinal cord.

PMID- 8300282
TI  - Spermatogenesis in Udonella (Platyhelminthes, Udonellidea) and the phylogenetic
      position of the genus.
AB  - Spermatids are joined (cytophores). Two centrioles lateral and/or proximal to the
      nucleus form axonemes, arranged parallel with each other, that extend into a
      short distal cytoplasmic process. The nucleus elongates, and mitochondria fuse to
      form a single elongate mitochondrion. The part of the spermatid containing the
      axonemes, nucleus and mitochondrion elongates to a thread-like spermatozoon,
      surrounded at its base (at the level near the basal bodies) by an arching
      membrane where the sperm detaches from the residual cytoplasm. At no stage are
      there free flagella (except for short free flagellar tips), an intercentriolar
      body or a median cytoplasmic process. A few peripheral microtubules and a compact
      dense body, not membrane bound and closely associated with the mitochondrion,
      were seen in spermatids. Spermiogenesis in Udonella is interpreted as derived
      from proximo-distal fusion by a shifting of the basal bodies deeper into the
      cytoplasm and a consequent loss of the median cytoplasmic process. Both the
      ultrastructure of the protonephridia and spermiogenesis indicate that Udonella
      does not represent the sister group of all other neodermatans, but is a
      secondarily modified "advanced" neodermatan. Lack of convincing synapomorphies
      indicates that the taxon Cercomeridea as a defined by Brooks (1989a, b) is
      invalid.

PMID- 8300283
TI  - Ultrastructural observations on the hamuli of the monogenean gill parasite
      Cichlidogyrus halli typicus.
AB  - The ultrastructure of a monogenean hamulus is described for the first time. The
      ultrastructure of the dorsal and ventral hamuli of the monogenean gill parasite
      Cichlidogyrus halli typicus (Price & Kirk, 1967, 76: 137-144) Revue de Zoologie
      et de Botanique Africaines Paperna, 1979 (Annales du Musee Royal del'Afrique
      Centrale 226: 1-31) is similar but there are differences between different
      regions of a single hamulus. Each hamulus has three layers in the middle of the
      hook region, a thin outer layer, a middle layer forming the bulk of the hook and
      a central core made up of longitudinally oriented rods. The central core
      disappears in the distal region of the hook and the outer layer is absent in the
      proximal region of the hook. Both the shaft and the roots consist of two layers,
      the inner layer of the shaft is made up of longitudinally oriented parallel rods,
      and the corresponding layer of the roots being composed of long fibrils. The
      longitudinally orientated rods of the central core may provide inner strength to
      resist the physical strain on the hook and the outer, and possibly the middle
      layers, may provide chemical resistance to host's tissue secretion. The distal
      region of each root is covered with a fibrous hood, which appear to be a
      specialized region for binding muscle fibres to the sclerite.

PMID- 8300284
TI  - Otobothrium penetrans (Cestoda; Trypanorhyncha) in the flesh of belonid fish from
      Philippine waters.
AB  - In April 1990, 488 marine fish belonging to 30 species from central Philippine
      waters were examined for flesh parasitic infections that may affect their
      consumability. One species of hemirhamphids and 3 species of belonids harboured
      plerocercoids of Otobothrium penetrans Linton, 1907 (Proceedings of the U.S.
      National Museum 33, 85-126). This is the first record of this parasite from
      Pacific fish species. The highest intensity of infection found was 8 in Tylosurus
      crocodilus. Most of the larvae were located between the dorsal spines of the
      vertebral column, only 32% were found in the fillets. Based on the present
      material we give a description of the plerocercoid stage of the species using
      scanning electron microscopy of the armature and morphometrical measurements.
      Comparison to results from earlier findings of O. penetrans by Linton (1907;
      1924, Proceedings of the U.S. National Museum 64, 1-114) and to O. kurisi by
      Shields (1985, International Journal for Parasitology 15: 635-643) lead to the
      conclusion that the latter species is a synonym for O. penetrans.

PMID- 8300285
TI  - Studies on host specificity in Paragonimus westermani: ultrastructural study of
      inflammatory reactions to the parasite in rat muscles.
AB  - Inflammatory reactions to the lung fluke, Paragonimus westermani, in an abnormal
      host, the rat, were studied by electron microscopy. Inflammatory cells
      accumulated around the worms in rat muscles, but the reaction varied
      significantly in intensity as well as distribution of inflammatory cells from
      worm to worm in the same and different hosts. In an accumulation of inflammatory
      infiltrates around the worm, eosinophils were more commonly seen, and neutrophils
      and macrophages were fewer in number. Mast cells appeared rarely. Where
      inflammatory cells touched to the worms, the tegument of the worms was covered
      with moderately electron-dense flocculent material which included dense granules.
      This material, which probably consisted of immune complexes of host antibody and
      antigen secreted from tegumental granules, seemed to block the inflammatory cells
      from adhering to the worm surfaces. Inflammatory cells made direct contact with
      worm surfaces where flocculent material was absent. Dense secretory material was
      discharged from some eosinophils as a result of degranulation.

PMID- 8300286
TI  - Species and morphs in the Ostertagiinae: an allozyme study of seven species.
AB  - Five enzymes, malate dehydrogenase, lactate dehydrogenase, mannose-phosphate
      isomerase, glucose-phosphate isomerase and phosphoglucomutase from seven putative
      species of Ostertagiinae were compared using starch-gel electrophoresis. The Nei
      distances were not much affected by origin of specimens or host species. Six of
      the putative species could form polymorphic pairs: Ostertagia ostertagi and
      Ostertagia lyrata, Ostertagia leptospicularis and Ostertagia kolchida,
      Teladorsagia circumcincta and Teladorsagia trifurcata. The Nei distance was of
      the same magnitude (> 0.6) between species pairs, O. ostertagi, O.
      leptospicularis, T. circumcincta and Spiculopteragia spp.

PMID- 8300287
TI  - Cryopreservation of Babesia divergens from jirds as a live vaccine for cattle.
AB  - A Babesia divergens live vaccine can be produced in jirds (Meriones
      unguiculatus). The major drawback of this live vaccine is the short shelf-life.
      We evaluated different methods for the cryopreservation of this vaccine. Blood
      from jirds infected with B. divergens was frozen to -196 degrees C using cooling
      rates of 1, 10, 30, 100, 196 and 250 degrees C min-1, and a two-step cooling
      rate. The cryoprotectants dimethyl sulfoxide (DMSO), polyvinylpyrrolidone 40 and
      glycerol were used at different concentrations. Aliquots were stored in liquid
      nitrogen for 10-20 days and rapidly thawed in a water bath at 40 degrees C.
      Infectivity of blood before and after cryopreservation was tested in jirds by
      i.p. inoculation. The prepatent periods recorded were used to calculate the
      infectivity of the inocula. The highest infectivity of 46% was recorded from
      blood cryopreserved with 3 M DMSO and cooled at 10 degrees C min-1. Infectivity
      of the frozen vaccine was tested in 4 heifers by inoculation of 2.5 x 10(7)
      parasites. All animals showed Ab titres 12 days after inoculation.

PMID- 8300288
TI  - A new species of Haliotrema (Monogenea: Ancyrocephalidae) from a Japanese puffer
      fish Takifugu niphobles (Tetraodontiformes: Tetraodontidae).
AB  - A new species of Haliotrema is described on the basis of material from the gills
      of the Japanese puffer fish Takifugu niphobles. The new species is compared to
      other ancyrocephalids from tetraodontid hosts and congeners with similar copulum
      morphology from unrelated hosts. It is distinguished from these species based on
      a combination of reproductive and haptoral characters. Comparison of the haptor
      musculature of the new species with that described for Haliotrema balisticus
      revealed a potential for additional taxonomic characters. Resolution of
      differences in the interpretation of the functional morphology of the muscle
      groups in the two species will require further investigation.

PMID- 8300289
TI  - The 3' terminal region of a gene encoding a cysteine-rich surface protein in
      Giardia duodenalis.
AB  - DNA derived from chromosome band 3 of the cloned Giardia duodenalis line, WB-1B
      was used to construct a cloned library in E. coli. One of these clones, C3/23,
      has been identified as the 3' coding region of a G. duodenalis cysteine-rich
      variable surface protein (CRVSP) gene by homology with other published CRVSPs and
      also contains 720 bp of the 3' flanking region. The sequence of C3/23, was
      derived from genomic DNA independently of cDNA, or expression copies of the CRVSP
      genes. The 3' flanking region is not homologous to the 3' untranslated regions of
      published CRVSPs which probably reflects its genomic origin. Subclones of C3/23
      were used to show that the 3' flanking region was conserved in all strains
      examined in this study and was repeated many times in the genome. The 3' flanking
      repeats were located on three chromosome bands and were not always associated
      with the coding sequence of C3/23 which was represented, although not equally, on
      all chromosome bands. The highly conserved nature of the 3' flanking region and
      its multiple representation in the genome emphasize the probable role of this
      sequence in the localization or regulation of expression of the CRVSPs in G.
      duodenalis.

PMID- 8300290
TI  - Identification of the microsporidian parasite, Enterocytozoon bieneusi in faecal
      samples and intestinal biopsies from an AIDS patient.
AB  - The microsporidian parasite, Enterocytozoon bieneusi, is currently recognized as
      a potentially important cause of chronic diarrhoea in patients infected with the
      human immunodeficiency virus (HIV). Faecal concentrates from a 38-year-old, HIV
      seropositive patient examined by light and electron microscopy revealed the
      presence of numerous microsporidian spores. The structural characteristics of the
      spores were consistent with those previously described for Enterocytozoon
      bieneusi. Each spore contained a single nucleus, a posterior vacuole and a polar
      filament with 6-7 overlapping coils which appeared in cross-section as a series
      of 3 doublets. Mature spores were surrounded by an inner unit membrane, an
      electron-lucent endospore and a thin, electron-dense exospore. The identity of
      the parasite was confirmed by the detection of unique endogenous developmental
      stages in duodenal biopsies. Both proliferative and sporogonial plasmodia
      (meronts and sporonts) were observed and all stages were monokaryotic (single
      nucleus) and apansporoblastic (sporophorous vesicle absent). Proliferative and
      sporogonial plasmodia divided by plasmotomy and spore organelles (polar filament,
      attachment disc and polaroplast) were well developed prior to fission of the
      sporogonial plasmodium.

PMID- 8300291
TI  - Strongyloides ratti: fumarate reductase and succinate dehydrogenase activities of
      infective larvae.
AB  - Submitochondrial particles prepared from axenised infective (L3) larvae of S.
      ratti (homogonic-strain) were assayed spectrophotometrically for fumarate
      reductase (FR) and succinate dehydrogenase (SDH) and their kinetic properties
      characterised. The S. ratti FR (pH 8.2; 37 degrees C) exhibited a maximum
      specific activity of 3.45 nmol (min)-1 (mg protein)-1 at a sodium fumarate
      concentration of 0.3 mM. Interestingly, the FR activity declined at fumarate
      concentrations greater than 0.3 mM. The mechanism of this unusual inhibitory
      effect requires further study. The S. ratti SDH (pH 8.2; 37 degrees C) showed a
      Vmax of 17.4 nmol (min)-1 (mg protein)-1; the Kmsucc was 0.5 mM. Although the
      SDH:FR ratio cannot predicate vectorial electron flow as would occur in vivo, an
      in vitro ratio of 5.04:1 was observed for SMPs derived from S. ratti L3 larvae.

PMID- 8300292
TI  - An alternative protocol for the serial passage and maintenance of a homogonic
      strain of Strongyloides ratti in female Sprague-Dawley rats.
AB  - A method which does not involve the tedious use of watch glass coprocultures for
      obtaining filariform infective (L3) larvae of Strongyloides ratti from faecal
      pellets of infected Sprague-Dawley rats is described. The alternative method
      utilises Baermannization (18 h) of faecal pellets to yield rhabditiform (L1)
      larvae of S. ratti and their subsequent culture for 72 h at 19 degrees C in
      tissue-culture-flasks containing only dechlorinated tap water to yield infective
      filariform (L3) larvae. The yields and infectivity of the L3 larvae obtained from
      the two methods were essentially similar.

PMID- 8300293
TI  - The efficacy of two electron transport inhibitors (720C80 and 993C76) on murine
      strongyloidiasis: a comparison with albendazole.
AB  - The clinical efficacy of albendazole (ABZ) in the treatment of chronic
      uncomplicated strongyloidiasis has been reported to be highly variable. In our
      murine model of strongyloidiasis a single oral dose of 5 and 10 mg kg-1 ABZ
      reduced (at day 4 post infection) the faecal larval count (FLC) by 54.2 +/- 12.5%
      and 81.5 +/- 10.2%, respectively. 100 mg kg-1 ABZ reduced the FLC by 100%. Two
      inhibitors of protozoan and filarial electron transport (720C80 and 993C76)
      inhibited the endogenous O2 consumption of intact infective (L3) larvae of S.
      ratti by > 50% at 2 x 10(-5) M in vitro, and reduced the FLC by 72 +/- 9.3% and
      62.0 +/- 10.3% respectively in vivo, at a dose of 70 mg kg-1. These results
      suggest that compounds designed as selective inhibitors of protozoan electron
      transport have significant efficacy against murine strongyloidiasis and may prove
      useful in the management of human strongyloidiasis.

PMID- 8300294
TI  - Susceptibility of two crossbreeds of sheep to Haemonchus contortus.
AB  - Studies were conducted on 20 crossbred lambs of 4-5 months old. Ten lambs were
      Nali x Corriedale cross (Hisardale) and the other 10 were Nali x Lohi cross
      (Munjal). Seven lambs each of both crossbreeds were infected with 10,000
      infective larvae of Haemonchus contortus. Three lambs of each crossbreed served
      as uninfected controls. Clinicopathological examinations were done before and
      after infection and all the lambs were necropsied 28 days post-infection. The
      body weight gain, haemoglobin and packed cell volume were significantly lower in
      Hisardale lambs and the peripheral eosinophil count was significantly higher in
      Munjal lambs. Significant hypoalbuminaemia and hypoglobulinaemia, a sharp
      increase in albumin: globulin ratio; significantly higher faecal egg counts;
      adult worm counts; abomasal pH, volume, congestion and oedema were observed in
      Hisardale lambs as compared to Munjal lambs. Clinical signs of haemonchosis were
      more severe in Hisardale lambs and two of them died. Munjal lambs therefore seem
      less susceptible than Hisardale lambs to H. contortus infection.

PMID- 8300295
TI  - Eosinophil differentiation in response to Fasciola hepatica and its
      excretory/secretory antigens.
AB  - Bone marrow cells from mice infected with Fasciola hepatica, from mice injected
      with F. hepatica excretory/secretory (ES) antigens, and from uninfected or
      uninjected control animals were cultured in the presence of F. hepatica ES
      antigens or the eosinophil differentiation cytokine IL-5. Eosinophil maturation
      in cultures was assessed quantitatively by measuring eosinophil peroxidase (EPO)
      activity and qualitatively by visual appraisal in stained preparations over a
      week. It was found that the presence in all cultures (including those from
      control animals) of either ES antigens at an optimal concentration of 100
      micrograms ml-1 (established in preliminary trials) or IL-5 at 500 units ml-1 led
      to enhanced EPO activity. EPO activity in cultures without IL-5 or ES antigens
      remained static or fell over the culture period. At day 3 in all cultures
      containing IL-5 or ES antigens, there was maintenance of or only a slight decline
      in, the number of eosinophils that were present when cultures were initiated, and
      more of them were mature than at day 0 as evidenced by their EPO activity.
      However, there was a marked fall in eosinophil numbers in all cultures in the
      absence of IL-5 or ES antigens. The results indicate that F. hepatica ES
      antigens, like IL-5, stimulate eosinophil maturation in bone marrow with a
      consequent rise in EPO activity in the cells. Whether the antigen(s) acts
      directly or indirectly on the eosinophils or their precursors has yet to be
      established. Nevertheless, it seems clear that F. hepatica produces a molecule
      with a functionally similar effect to that of IL-5.

PMID- 8300296
TI  - Isolation, initial characterization and serological studies of glycolipid
      antigens from Babesia bovis-infected erythrocytes.
AB  - Serological analysis of Babesia bovis-derived glycolipids by ELISA and the
      indirect fluorescent antibody technique demonstrated the existence of their
      antigenic and immunogenic activities not only in B. bovis but also in B. bigemina
      infections. This indicates that serological cross-reactivity of B. bovis and B.
      bigemina relates to glycolipids. The negative ELISA reaction obtained with
      Anaplasma marginale antisera suggested the specificity of the reaction to the
      genus Babesia. Fractionation of these glycolipids by Florisil Sep-Pak column
      chromatography with subsequent HPTLC immunostaining and Orcinol staining
      suggested the presence of carbohydrate antigenic determinants in B. bovis
      glycolipids.

PMID- 8300297
TI  - Persistence of acquired immunity to Trichostrongylus colubriformis in sheep after
      termination of infection.
AB  - Lambs were infected with 6000 Trichostrongylus colubriformis L3 per week for 18,
      12 or 6 weeks, beginning at ages 14, 20 and 26 weeks, respectively. At the end of
      the primary infection subgroups had geometric mean adult worm burdens of 5000,
      15,000 and 18,000, respectively. In the remaining sheep the worm population was
      removed with anthelmintic, and sheep had no further larval intake until
      challenged with T. colubriformis 1, 6, 12, 18 or 24 weeks later. In the groups
      given 18 or 12 weeks primary infection, establishment of challenge doses was low
      (less than 25% of establishment in helminth naive controls) in most animals at
      all challenge times. However, for the groups given 6 weeks primary infection,
      establishment was low only at the first two challenge times. Thereafter it had
      similar mean to control groups, but much greater variance. Other subgroups were
      challenged with T. colubriformis, Ostertagia circumcincta and Haemonchus
      contortus 1 week after worm removal. In these animals T. colubriformis
      establishment was not different to animals challenged at the same time with T.
      colubriformis alone, however immunity to T. colubriformis afforded little
      protection against the other species. The results of this experiment were
      incorporated into a simulation model of the population dynamics of T.
      colubriformis.

PMID- 8300298
TI  - Nucleoside transport in Crithidia luciliae.
AB  - Nucleoside transport was evaluated in the trypanosomatid Crithidia luciliae by a
      rapid sampling technique. C. luciliae was shown to possess two independent
      nucleoside transporters, one which transported adenosine, deoxyadenosine,
      tubercidin, sangivamycin and the pyrimidine nucleoside thymidine, while the
      second was specific for guanosine, inosine and deoxyguanosine. The rapid influx
      occurred by a process of facilitated transport. The apparent Km values for
      adenosine and guanosine were 9.34 +/- 1.30 and 10.6 +/- 2.60 microM,
      respectively. The pyrimidine nucleoside thymidine was transported at a rate
      approximately 50% lower than the purine nucleosides, whilst uridine, deoxyuridine
      and deoxycytidine were not transported. The optical isomer, L-adenosine entered
      the organism by simple diffusion rather than by facilitated transport. In
      contrast to mammalian cells, neither of the nucleoside transporters in C.
      luciliae were inhibited by nitrobenzylthioinosine, dilazep, or dipyridamole,
      potent inhibitors of nucleoside transport in mammalian cells, whilst p
      chloromercuribenzoate sulphonate inhibited both nucleoside transporters in C.
      luciliae.

PMID- 8300299
TI  - An attempt to protect cats against infestation with Ctenocephalides felis felis
      using gut membrane antigens as a vaccine.
AB  - Cats (n = 5) were vaccinated with membrane antigens extracted from the gut of
      unfed fleas (Ctenocephalides felis felis) together with Quil A and RIBI as
      adjuvants. Five unvaccinated cats were retained as controls. All the cats were
      infested on 6 separate occasions with fleas (46-250 per challenge). Protection
      was assessed from the number of fleas retrieved and the fecundity of the female
      fleas, measured as the number of developed oocytes contained in the reproductive
      tract. Cats injected with gut membrane antigens had significantly elevated levels
      of anti-flea antibodies in their sera, but they were neither protected
      significantly against infestation with fleas nor was the apparent fecundity of
      fleas which had fed on vaccinated cats decreased. The possible reason why gut
      membrane antigens failed to protect cats against fleas are discussed.

PMID- 8300300
TI  - Lack of intraspecific variation in the second internal transcribed spacer (ITS-2)
      of Trichostrongylus colubriformis ribosomal DNA.
AB  - The nucleotide sequence of the second internal transcribed spacer (ITS-2) was
      determined for three populations of the parasitic nematode Trichostrongylus
      colubriformis which differed in their susceptibility to benzimidazole
      anthelmintics and/or in their geographical origin. No intraspecific variation was
      found in the ITS-2 sequence, indicating that this region of rDNA is inadequate to
      discriminate between resistant and susceptible populations of T. colubriformis,
      but it may prove useful for distinguishing between species of Trichostrongylus.

PMID- 8300301
TI  - Host effects on glutathione S-transferase activity in Fasciola hepatica.
AB  - Glutathione S-transferases (GST, E.C. 2.5.1.18) in Fasciola hepatica from sheep
      were previously found to be extremely variable with regard to specific GST
      activity and isoenzyme profile within and between parasite isolates. The effect
      of the host on GST activity and isoenzyme profile was examined by infecting mice,
      rats and cattle as well as sheep with one or the other of two isolates--either
      salicylanilide-resistant or salicylanilide-susceptible F. hepatica. In the case
      of both isolates, GST activity in hosts relatively resistant to reinfection--rats
      and cattle--was lower and more restricted in range compared with hosts
      susceptible to multiple infection--mice and sheep. In the case of the rat flukes,
      there was little variation in isozyme profiles whereas cattle flukes appeared to
      exhibit more variation than sheep flukes. In mice, despite the apparent
      variability in GST activity, only one GST band was found in the isoenzyme
      profiles. Therefore, the host appears to exert a pronounced effect on the
      activity and expression of GSTs in F. hepatica which may be related to variation
      in the immune responses of the different hosts during infection.

PMID- 8300302
TI  - In vitro effects of Fasciola hepatica on the main functions of polymorphonuclear
      leukocytes: chemotaxis and free radical generation induced by phagocytosis.
AB  - The effects of adult fluke excretions-secretions (ES) on two major functions of
      circulating bovine polymorphonuclear (PMN) cells were investigated. Under
      agarose, PMN chemotaxis was not affected by the ES. ES preincubated with PMN for
      15, 30 or 60 min at 37 degrees C, before a chemoluminescence assay, inhibited
      phagocytosis and/or free radical generation in a dose and time dependent manner.

PMID- 8300303
TI  - Sphingomyelin synthesis in Ascaridia galli.
AB  - Adult Ascaridia galli incorporate label from [U-14C] serine into various
      intermediates of sphingomyelin synthesis (ketosphinganine, sphinganine,
      sphingosine, ceramide and sphingomyelin). From the results it is concluded that
      A. galli possesses the five enzymes involved in sphingomyelin synthesis, namely:
      serine palmitoyltransferase, 3-ketosphinganine reductase, flavoprotein
      sphinganine reductase, sphingosine acyltransferase and ceramide choline
      phosphotransferase.

PMID- 8300304
TI  - Allozyme variations between sheep or rabbit laboratory reared and goat wild
      populations of Trichostrongylus colubriformis.
AB  - Allozyme variation at 3 polymorphic enzyme loci (GPI, PGM, MDH) was studied in
      Trichostrongylus colubriformis. By means of a multivariate analysis it was shown
      that populations of worms harboured by naturally infected goats were genetically
      different from populations laboratory reared in lambs or rabbits. A deficiency of
      heterozygotes was recorded in each population studied.

PMID- 8300305
TI  - Chester Albern Herrick. 1893-1955.

PMID- 8300307
TI  - Molecular characterisation of peanut agglutinin-binding glycoproteins from
      Eimeria tenella.
AB  - A group of glycoproteins, which strongly bind peanut agglutinin (PNA) was found
      in Eimeria tenella. Two major antigenic glycoproteins, Et110gp and Et35gp, were
      identified in sporulated oocysts and sporozoites. Molecular characterisation of
      carbohydrate moieties (lectin binding, enzymic hydrolysis and monosaccharide
      composition) revealed that both glycoproteins are rich in galactose and N
      acetylgalactosamine, and appear to be sialylated. Both glycoproteins were
      susceptible to treatment with neuraminidase followed by O-glycosidase, suggesting
      that the oligosaccharide chains are attached to the protein by an O-glycosidic
      linkage to serine and/or threonine. Purified Et35gp contained a large number of
      serine (14) and threonine (33) residues, and was rich in glycine. This protein
      aggregated after repetitive lyophilisation and migrated on SDS-PAGE gels as an
      85,000 protein. Sera against purified Et35gp raised in chickens and rabbits, and
      anti-E. tenella immune chicken serum recognised both antigens on blots and on the
      surface of sporozoites. Chickens immunised with purified Et35gp were not
      protected against coccidial infection.

PMID- 8300306
TI  - Fasciola hepatica: a secreted cathepsin L-like proteinase cleaves host
      immunoglobulin.
AB  - Adult Fasciola hepatica secrete a cysteine proteinase capable of cleaving host
      IgG close to the papain cleaving site. The proteinase was separated by size
      permeation chromatography. Gelatin-substrate polyacrylamide gel electrophoresis
      analysis revealed that the proteinase migrates as 6 proteolytic bands in the
      apparent molecular size range 60-90 kDa. Based on pH profiles of activity,
      inhibition studies using diethylpyrocarbonate and the diazomethylketone Z-phe-ala
      CHN2, and characterising the substrate specificity of the enzymes using
      fluorogenic peptide substrates we have shown that the 60-90-kDa proteinases are
      cathepsin L-like proteinases.

PMID- 8300308
TI  - The effect of cyclosporin A on Angiostrongylus cantonensis infection and
      eosinophilia in mice.
AB  - Male BALB/c mice were infected with Angiostrongylus cantonensis and at various
      times p.i. treated with cyclosporin A (CsA) either for 5 days continuously or
      intermittently, or for 12-16 days on alternate days. They were monitored for
      peripheral blood eosinophilia and at necropsy examined for CSF and bone marrow
      eosinophilia, and worm recovery. CsA treatment provoked a transient inhibition of
      peripheral blood eosinophilia in all groups examined, followed by rebounding
      eosinophilia. There was no significant difference in bone marrow and CSF
      eosinophilia between CsA- and vehicle-treated groups. Mice treated with CsA on
      alternate days yielded lower intracranial worm recovery with small-sized worms at
      days 7, 21 and 30 p.i. than vehicle-treated groups did. No significant reduction
      in worm recovery was noted in mice treated for 5 days either continuously or
      intermittently, although worms, especially female ones, harvested from groups
      treated with CsA from days--1 to 3 or from days 13 to 17 were significantly
      smaller than those from vehicle-treated groups. CsA-treatment suppressed
      blastogenic responses of spleen cells against Con A or worm antigen at days 7 and
      21 p.i. In vitro treatment of the 3rd stage larvae with CsA did not adversely
      influence survival of A. cantonensis in mice. These data indicate that CsA exerts
      anti-parasitic effects against A. cantonensis in mice.

PMID- 8300309
TI  - Preliminary report: suspicion of hearing-loss at age 0-1 years by TV viewing
      attitude.
AB  - To determine any difference of TV viewing attitude between normal and hearing
      loss children, 14 normal and 8 sensory impaired infants/toddlers were observed
      separately in a playroom with a TV set showing a 12-min videotape. All children
      enjoyed TV and showed clear differences in TV viewing behavior between hearing
      loss and auditory normal children. At the beginning of their favorite programs or
      changes in programs, normal infants/toddlers were quickly aware of the TV sound
      and turned toward the TV set, where as hearing-loss children remained unaware.
      Our observation proved the intact hearing of two clients who had not responded to
      regular infant auditory tests. Moreover, we surveyed 65 hearing-loss children.
      Only 21% of them began to watch TV at 0 year of age, 50% at 1 year. They did it
      apparently later than normal infants who began to watch TV mostly before 1 year
      of age in the Japanese general population. From fitting with a hearing aid,
      however, most of them began to enjoy TV, watch it longer, have their favorite
      programs (music, songs, etc.) and turn to face the TV whenever a favorite program
      began. This suggests hearing acuity is important to enjoy TV. Since TV is already
      familiar and attractive to most any children, it is a useful and sensitive tool
      for early detection of hearing-loss children at 6-18 months of age.

PMID- 8300310
TI  - Posterior glottic stenosis in children.
AB  - The management of posterior glottic stenosis resulting from impaired crico
      arytenoid joint (CAJ) mobility in infants and children presents a perplexing and
      frequently unrewarding surgical dilemma; any improvement in the airway is almost
      invariably at the expense of the voice. Progress in this area has been hampered
      not only by the rarity of cases, but also by the technical difficulty of
      achieving an accurate diagnosis at endoscopy. In order to address this problem we
      have undertaken a retrospective analysis of 35 infants and children, treated at
      Great Ormond Street between 1980 and 1991, with endoscopically confirmed
      impairment of CAJ mobility. Five cases of mild posterior glottic stenosis were
      successfully treated either conservatively or by laser scar division. Thirty
      cases of moderate or severe stenosis were identified, and 19 of these have
      undergone corrective surgery. Of these 19, 17 had a prior tracheostomy, and 12
      have been decannulated. No problems with aspiration were encountered but five
      (i.e. 25%) of those treated surgically suffered a deterioration of voice quality.

PMID- 8300311
TI  - The results of functional endoscopic sinus (FES) surgery on the symptoms of
      patients with cystic fibrosis.
AB  - The relationship between cystic fibrosis (CF) and sinus disease has been
      appreciated since at least 1959. Unfortunately the standard methods used to treat
      sinus disease have been very unrewarding in the CF patients. We evaluated the
      long-term results achieved on 17 patients with CF that underwent FES surgery
      between July 1988 and January 1991. This group consisted of 16 pediatric and 1
      adult patients with previously diagnosed CF, documented chronic sinus disease and
      nasal polyposis that had failed long-term maximal medical management. The
      patients, or their parents, were contacted and asked to rate the severity and
      frequency of their symptoms associated with chronic sinus disease, pre- and
      postoperatively. The specific symptoms evaluated were nasal obstruction, nasal
      discharge, postnasal drip, halitosis and cough. In addition, we attempted to
      measure the number of hospitalizations and the presence and frequency of
      headaches. We were able to show that, while there was no change in the relative
      health of patients as measured by the number of hospitalizations, there was a
      significant improvement in the quality of life. There was a marked decline in the
      frequency of nasal obstruction, nasal discharge and postnasal drip and a high
      level of patient satisfaction with the procedure. No changes were seen in the
      frequency or nature of the cough, halitosis or headache.

PMID- 8300312
TI  - The intrinsic response of the cricoid cartilage to vertical division.
AB  - The explanation for the separation in the cricoid cartilage after the anterior
      cricoid split procedure has been a matter of speculation. Whether it is caused by
      extrinsic factors such as stenting, contraction of laryngeal muscles, fibrosis,
      or whether it is due to the intrinsic nature of the cricoid cartilage itself has
      yet to be defined. Whole organ in vitro cultures of juvenile gerbil cricoid
      cartilages were utilized to study the intrinsic response of cricoid cartilage to
      anterior vertical division. Our results showed the cricoid cartilage to
      immediately separate, and that separation to markedly increase during whole organ
      culture. These results suggest that while extrinsic factors may modify the gap
      after the anterior cricoid split procedure, the intrinsic nature of the cricoid
      cartilage itself results in the gap formation.

PMID- 8300313
TI  - Infant feeding and phonologic development.
AB  - The relationship between breastfeeding and speech development was examined to
      determine what duration (if any) of breastfeeding is associated with better
      performance on a measure of phonologic development. Twenty-nine children aged 36
      48 months and their parents were recruited from preschools to serve as subjects.
      The children's durations of exclusive breastfeeding ranged from 0 (always bottle
      fed) to 6 months. Phonologic development was assessed using an instrument known
      as the Percentage of Consonants Correct (PCC) [12]. Feeding histories were
      obtained by retrospective interviews with parents. Parents and teachers also made
      ratings of children's speech and total communication on a 5-point scale. This
      study fails to replicate earlier researchers' findings of an association between
      breastfeeding and phonologic development. No evidence was found of an association
      between any duration of either exclusive or partial breastfeeding and PCC scores.
      Pearson r correlations between parents' and teachers' ratings and PCC scores were
      weak. Results are discussed in comparison with previous reports of a correlation
      between breastfeeding and phonologic development.

PMID- 8300314
TI  - Radiation therapy as an alternative to surgery in the management of intracranial
      juvenile nasopharyngeal angiofibroma.
AB  - Juvenile nasopharyngeal angiofibroma is a benign, vascular tumor which typically
      presents in adolescent males. Although surgical resection is usually recommended
      for the management of this tumor, external beam radiation therapy has also been
      advocated in the literature. We report three cases of large juvenile
      nasopharyngeal angiofibromas with extensive intracranial extension primarily
      managed with external beam radiation therapy. Although there was not complete
      resolution of the tumors, there was significant alleviation of symptomatology
      with no serious side effects from the radiation therapy. Based on these cases, we
      feel that external beam radiation therapy in the management of extensive juvenile
      nasopharyngeal angiofibromas with intracranial extension is warranted in certain
      select cases.

PMID- 8300315
TI  - Congenital internal carotid artery aneurysm.
AB  - Congenital carotid aneurysms are frequently found in the intracranial arteries
      but rarely seen in extracranial part of the internal carotid artery. A case of a
      congenital internal carotid artery aneurysm at the skull base was treated in a 13
      year-old female child. This case is being presented for its rarity and also to
      highlight the ease of exposing the upper end of the aneurysm via lateral skull
      base approach. Infratemporal fossa approach was adopted in this case. The carotid
      canal was drilled off and the upper end of the aneurysm in the intrapetrous part
      was mobilized and vascular clip applied before dissection of the aneurysm.
      Relevant literatures pertaining to this case are also reviewed.

PMID- 8300316
TI  - Mastoiditis caused by atypical mycobacteria.
AB  - Three case reports of mastoiditis caused by atypical mycobacteria are discussed
      and a review of the world literature is given. Our aim is to focus the attention
      of the ENT specialist and the pediatrician on these pathological agents in
      unilateral recurrent otitis media. The case reports illustrate the importance of
      histologic and microbiologic examination. Difficulties in the differential
      diagnosis are mentioned. The therapy is slightly different from lymphadenitis
      caused by atypical mycobacteria because for mastoiditis we prefer the combination
      of surgery with medical treatment.

PMID- 8300318
TI  - Nasal hamartoma: case report and review of the literature.
AB  - Nasal masses in the pediatric population present with nasal obstruction,
      epistaxis and chronic rhinorrhea. We report on a 6-year-old boy with long
      standing nasal obstruction. A large left nasal mass was evident on physical
      examination and CT scan. Techniques of functional endoscopic sinus surgery were
      used to resect the mass, which, on pathologic examination, proved to be a
      hamartoma. Hamartomas are non-neoplastic malformations, or inborn errors of
      tissue development. They are characterized by an abnormal mixture of tissues
      indigenous to that area of the body. Review of the literature revealed 5
      previously reported cases of nasal hamartomas, only 2 of these in children. Our
      case is unique in that the hamartoma arose from the ethmoid and maxillary
      sinuses; previously reported cases arose from the septum and vestibule. This is
      the first reported case treated using a functional endoscopic sinus surgery
      approach.

PMID- 8300319
TI  - The role of orthodontic extrusive remodeling in the enhancement of soft and hard
      tissue profiles prior to implant placement: a systematic approach to the
      management of extraction site defects.
AB  - A classification scheme that systematizes the wide range of regenerative
      potential of common extraction site topographies is presented. Within this
      system, the parameters for immediate implant placement and preliminary ridge
      augmentation are discussed. In addition, a new adjunctive role for orthodontic
      extrusion is introduced. This approach is intended to manipulate "hopeless" teeth
      to modify their local defect environments, thereby enhancing the predictability
      of subsequent implant placement at those sites.

PMID- 8300317
TI  - Sudden infant death and acute posterior lingual inflammation.
AB  - A case is described of sudden and unexpected death in a 5-month-old boy who was
      found to have acute inflammation with multifocal abscess formation at the base of
      his tongue adjacent to the epiglottis. The case demonstrates the vulnerability of
      the upper aerodigestive tract in infancy to possible anatomic or functional
      obstruction from intrinsic lesions and draws attention to the potentially lethal
      effects of critically-placed posterior lingual inflammation.

PMID- 8300320
TI  - A survey of natural tooth abutment intrusion with implant-connected fixed partial
      dentures.
AB  - To elicit information about the phenomenon of intrusion of natural tooth
      abutments in implant-connected prostheses, a survey was distributed to clinicians
      with varied experience. Although practitioners with more experience in
      fabricating implant-supported dentures connected to natural teeth reported fewer
      instances of intrusion, it cannot be concluded that this observation is
      significant. The cause of intrusion is probably multifactorial, and respondents
      suggested several possible causative factors: disuse atrophy, debris impaction,
      impaired rebound memory, and mechanical binding. Because apical migration of
      abutment teeth affects occlusion and oral hygiene, the authors make several
      recommendations for treatment planning for patients who have natural dentition
      adjacent to proposed implant sites.

PMID- 8300321
TI  - The emergence margin in prosthetic reconstruction of periodontally involved
      teeth.
AB  - This paper reviews types of preparation margins and the placement of the
      restoration's margins in relation to the gingival margin in prosthetic
      reconstruction of periodontally involved teeth. The "emergence margin," a new
      type of preparation margin, is presented through three case reports. The
      requirements for successful use of the emergence margin are discussed.

PMID- 8300322
TI  - The enhancement of guided tissue regeneration by altering root surface
      topography.
AB  - The periodontal fenestration model was used in four young mongrel dogs to
      evaluate the ability of vertical root surface grooving to enhance and direct cell
      outgrowth and subsequent formation of new attachment at 2- and 6-week healing
      intervals. In each dog, three fenestration wounds were made on each side of the
      mandible. On the control side, the roots were planed to dentin, a barrier
      membrane was sutured over the wound, and the flaps were replaced over the
      membrane. The experimental side received three vertical grooves followed by
      membrane placement and flap replacement. Histologic and histometric analyses were
      performed to determine the amount of new bone, cementum, and ankylosis and
      maturation of wound healing. Grooved wounds demonstrated greater cementum and
      bone formation, primarily in the early wounds, in addition to a more mature
      attachment at 6 weeks. Grooving the root surface may enhance initial cell
      adhesion and proliferation, thereby accelerating new attachment formation.

PMID- 8300323
TI  - Gingival augmentation using guided tissue regeneration: two case reports.
AB  - Two cases are presented to illustrate a technique for the use of the principles
      of guided tissue regeneration for root coverage and gingival augmentation in
      humans. The paper discusses the advantages of GTR over a variety of conventional
      root coverage techniques.

PMID- 8300324
TI  - A comparison of glass-ionomer cement and calcium hydroxide liners in amalgam
      restorations.
AB  - This study compared the caries inhibition and microleakage of two liners under
      amalgam restorations. Thirty-two molars received mesio-occlusal and disto
      occlusal Class II cavity preparations. Calcium hydroxide was randomly placed as a
      liner in one preparation of each tooth and glass-ionomer cement liner was placed
      in the other. Amalgam restorations were placed. Teeth were axially loaded and an
      acid-protective varnish was placed. Teeth were placed into artificial saliva for
      3 months, thermocycled, and cycled through a caries challenge. Sections were
      obtained from 20 teeth and photographed under polarized light. The remaining
      teeth were placed in 2% basic fuchsin and sectioned. A t-test indicated that
      restorations with glass-ionomer cement liners exhibited significantly less
      demineralization and microleakage than did restorations with calcium hydroxide
      liners.

PMID- 8300325
TI  - Is there a hypocholesterolemic factor in milk and milk products?
AB  - Cow's milk is considered to be related to atherosclerosis since more than 50% of
      its energy comes from fat in which saturated fatty acids are predominant. But
      many investigators have reported that milk or milk products have actually a
      hypocholesterolemic effect in man and animals and a number of milk constituents
      have been suggested as hypocholesterolemic factors.

PMID- 8300326
TI  - Assessment of vitamin A status in pregnant women as reflected by in vitro
      destruction of vitamin A by hemolysates and urinary ammonium nitrogen to
      creatinine ratio.
AB  - To investigate the significance of the lowered plasma vitamin A during the last
      few weeks of pregnancy, the capacity of erythrocyte lysates to destroy vitamin A
      in vitro and the alteration in ammonium nitrogen to creatinine ratio (Am N/Cr) in
      random urine samples was followed up at different gestational ages in women from
      low income groups. One group received no supplementation and the other received
      supplements of 1800 retinol equivalents (RE) and at most points the number of
      observations were not less than 12. In the unsupplemented women there was a
      significant increase in the capacity of erythrocytes to destroy vitamin A in
      vitro, which reflects an increased oxidative stress as compared to the
      supplemented group. While differences in mean Am N/Cr did not follow any
      consistent pattern, there was a strong association between lowered plasma vitamin
      A (< 35 micrograms/dl) and increased Am N/Cr ratio (> 0.5). This was true only
      when combined data of both groups were considered till 26 weeks of gestation and
      not beyond. As expected in supplemented women there was no significant fall in
      the plasma vitamin A during term. These data reveal that the lowered plasma
      vitamin A levels are suggestive of greater risk of hypovitaminosis A during
      pregnancy as indicated by the oxidative stress in erythrocytes.

PMID- 8300327
TI  - Hepatic or pulmonary ornithine decarboxylase and vitamin A status in Wistar rat,
      enzyme kinetics--influence of chloroform.
AB  - The ODC activity, initial enzyme in the polyamines synthesis, was studied in the
      liver and lungs of Wistar rat under avitaminosis A. In the liver: ODC activity is
      decreased by vitamin A deficiency but partially recovered with retinol repletion
      during 2 weeks. An intraperitoneal injection of chloroform markedly stimulates
      the ODC activity, as in the deficient rat as in the normal animal; the response
      following stimulation is even relatively higher under avitaminosis A. The Km
      value of ODC increases in the deficiency; intermediate values are obtained in
      retinol repletion. However the chloroform injection has no effect on the Km
      values under any of the nutritional state. In the lungs: The baseline ODC
      activity is slightly decreased in the deficient animals. The chloroform
      stimulation induced relatively a moderate increase in the normal rat (2 fold over
      baseline level); it is more intense (4 fold) in deficient animal and the ODC
      activity is well above those of normally fed control in absolute value. As in the
      liver, the enzyme Km increases in avitaminosis A and a retinol repletion
      partially attenuates this influence. Here again, the chloroform stimulation has
      no effect on the Km values.

PMID- 8300328
TI  - Effects of vitamin E and fat supplementation on concentration of vitamin E in
      plasma and milk of sows and in plasma of piglets.
AB  - Twenty-seven (Yorkshire) gilts, on a corn-soybean diet up to 57 d of gestation,
      were assigned to 3 treatment groups. Group 1 received no fat, Group 2 were
      supplemented with 5% tallow and Group 3 with 5% fish oil. Each group was
      supplemented with 0.1 ppm Se and 22, 44 or 88 IU of dl-alpha-tocopherol
      acetate/kg of feed. Samples of gilts' blood were taken at 57, 78 and 99 days of
      gestation, parturition, 14 and 28 d later. Similarly, first colostrum and milk
      (14 and 28 days postpartum) were sampled. Blood samples were also taken from the
      newborn piglets and at 14 and 28 d post natally. Increasing gilts' dietary
      vitamin E concentrations during gestation and lactation increased alpha
      tocopherol levels in the plasma (P < 0.05). No statistical difference was
      observed (P > 0.05) in gilts' plasma alpha-tocopherol concentration at any blood
      sampling time among dietary fat treatments. Dietary fat did not affect alpha
      tocopherol concentrations in colostrum or milk (P > 0.05). Overall the effect of
      vitamin E supplementation was linear in the milk at 14 and 28 d of sampling. The
      level of alpha-tocopherol in the colostrum was much higher than in milk. At birth
      piglet tocopherol concentrations were very low, perhaps because little tocopherol
      crosses the placental barrier. At day 14 piglet plasma tocopherol concentrations
      increased about 4-fold (P < 0.01) with a tendency for a greater concentration in
      piglets sucking gilts receiving higher levels of alpha-tocopherol. Dietary
      effects were not found to be significant (P > 0.05).

PMID- 8300330
TI  - Use of smokeless tobacco and cigarettes--effects on plasma levels of antioxidant
      vitamins.
AB  - In a population-based sample of 40-49-year-old men, plasma levels of antioxidant
      vitamins were measured in 17 regular users of smokeless tobacco (oral snuff), 26
      regular smokers and 54 non-tobacco users. Vitamin intake by tobacco use was
      assessed by a food frequency questionnaire in 174 men in the 40-49 year age
      range. Compared with non-tobacco users, snuff dippers had similar plasma levels
      of ascorbate, tocopherols and carotenoids, whereas these were all significantly
      reduced in smokers. Smokers, but not snuff dippers, had plasma levels of
      ascorbate significantly below those expected from ascorbic acid intake,
      indicating enhanced expenditure of ascorbate in smokers but not in snuff dippers.
      The results show that plasma levels of antioxidant vitamins are not reduced in
      snuff dippers as they are in smokers, possibly as the combined result of higher
      intake and lower expenditure of ascorbate and tocopherols in those who use
      smokeless tobacco.

PMID- 8300329
TI  - Vitamin E and selenium deficiencies increase indices of lipid peroxidation in
      muscle tissue of ruminant calves.
AB  - Indices of lipid peroxidation were investigated in muscle tissues of 1) calves
      depleted of vitamin E and/or Se and 2) calves depleted of vitamin E and Se and
      fed daily supplements of polyunsaturated fatty acids (PUFA). Calves deficient in
      both vitamin E and Se or deficient in vitamin E alone showed elevated muscle
      concentrations of thiobarbituric acid-reactive substances (TBARS), ascorbate
      induced TBARS (ATBARS), ascorbate-induced hexanal and iron-induced 4
      hydroxynonenal (HNE). Muscle tissue of calves depleted of Se alone showed no
      increases in these indices of lipid peroxidation. Two further groups of calves
      were fed diets either sufficient or deficient in both vitamin E and Se. Both of
      these groups were then fed linseed oil, protected against ruminal hydrogenation,
      as a source of PUFA. The deficient animals had higher muscle concentrations of
      all three indices of lipid peroxidation than the supplemented calves.
      Furthermore, feeding PUFA to vitamin E and Se deficient animals increased muscle
      concentrations of induced HNE to levels above those in deficient animals not fed
      PUFA supplements.

PMID- 8300331
TI  - Vitamin B12, folic acid and haematological status of 132 Thai vegetarians.
AB  - Serum vitamin B12, folic acid and haematological variables of 132 Thai
      vegetarians (64 males and 68 females) were investigated. Forty-seven healthy
      omnivorous individuals served as controls. No statistical differences in
      haemoglobin concentration, packed red cell volume and mean corpuscular
      haemoglobin concentration between the vegetarians and controls had been detected.
      In the female vegetarians, the haemoglobin concentration and packed red cell
      volume were, however, statistically lower. No significant differences in the
      white cell counts and platelet counts were observed in both groups. A significant
      increase of basophilic stippling and reticulocytes was observed in the
      vegetarians. Serum vitamin B12 decreased and serum folic acid levels increased
      according to the duration of vegetarianism in the vegetarians. In the females
      practicing vegetarianism for 6-10 years or more, the proportion of serum vitamin
      B12 deficiencies was particularly high. The high percentage of vitamin B12
      deficiency in the vegetarians might be related to megaloblastic anaemia. This
      form of anaemia is commonly associated with the presence of basophilic stippling.
      Therefore, the increased presence of basophilic stippling and reticulocytes might
      indicate a mild stage of this type of anaemia among the vegetarians.

PMID- 8300332
TI  - Synthesis and antiscorbutic activity of vitamin C analogue: L-threo-hex-2-enaro
      1,4-lactone ethyl ester in the guinea pig.
AB  - L-threo-hex-2-enaro-1,4-lactone ethyl ester (II) was synthesized by the modified
      Fisher's esterification and its sodium salt was obtained almost quantitatively.
      Confirmation of the compound was made by elementary analysis, as well as IR, UV,
      MS and NMR spectra. The antiscorbutic activity was compared to that of ascorbic
      acid and the result showed that (II) did not have Vitamin C activity. The results
      of this investigation indicate that a close relationship exists between the
      chemical structure of the C-6 position of ascorbic acid analogues and the
      development of vitamin C activity.

PMID- 8300333
TI  - The effects of periconceptional folic acid and vitamin supplementation on
      maternal folate levels and on neurulating hamster embryos in vivo.
AB  - We studied the effects of periconceptional oral supplementation of folic acid and
      vitamins on the maternal red blood cell (RBC) folate level of golden hamsters
      (Mesocricetus auratus, Waterhouse). The effects of folate deficiency and
      supplementation on the process of neurulation and the incidence of resorptions
      were evaluated. Groups of at least eleven mature virgin female hamsters were
      placed on one of six specific regimens which started two weeks prior to mating
      and continued until sacrifice on day nine of pregnancy. Just prior to sacrifice,
      blood samples were drawn by cardiac puncture to measure maternal folic acid
      levels in red blood cells. The staging of the embryos was based on O'Rahill's
      modification of Streeter's developmental horizons in human embryos. Considerable
      variation was observed in the stage of embryonic development of 9-day-old hamster
      embryos, both between littermates and between litters of the same gestational
      age. A high overall incidence of open neural tubes was observed, which did not
      reflect neural tube closure failures. A folate-free diet caused retardation of
      the embryonic development, although maternal folate levels were unaffected (p <
      0.01). The RBC folate levels in the animals which received oral supplementation
      with folic acid was significantly higher than that in the unsupplemented controls
      (p < 0.001). Folic acid supplementation alone increased the RBC folate level
      significantly more than combined supplementation with multivitamins (p < 0.001).
      The data indicate that oral supplementation with folic acid and/or multivitamins
      produce adequate maternal RBC folate levels. An inadequate maternal folate intake
      can affect the growth of neurulating embryos even if the maternal RBC folate
      levels are still sufficient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300334
TI  - Reverse phase open column chromatography determination of urinary riboflavin.
AB  - Reverse phase open column chromatography was used to determine urinary
      riboflavin. An aliquot of a urine specimen was added directly onto the reverse
      phase open column. The riboflavin was collected and measured as the compound was
      eluted. The mobile phase (MeOH/H2O/HOAc 37/63/0.1 v/v/v) and stationary phase
      (C18, 50 microns) were used. The method shows good reproducibility. Recovery of
      added Vit.B2 was 98.89-100%. The coefficient variation of reproducibility of
      within day was 1.53%. The coefficients of variation of reproducibility of day-to
      day were 0.39% and 1.74% for low and high concentration samples, respectively.
      The reverse phase open column chromatography was compared to the traditional
      fluorometric method and HPLC method for riboflavin. The coefficient of linear
      regression of these comparisons are Y = 0.331 + 1.010X (n = 37, r = 0.984) and Y'
      = -0.004 + 1.036X' (n = 15, r = 0.999) for RP open column vs. traditional method
      and RP open vs. HPLC, respectively, where X or X' is the reverse phase open
      column chromatography method and Y or Y' is the traditional fluorometric method
      or HPLC, respectively. Concentrations of riboflavin as low as 0.05 micrograms/ml
      were measured with a linear relation of response to concentration to at least 10
      micrograms/ml.

PMID- 8300335
TI  - Cholesterol peroxidation potential as influenced by dietary fat type.
AB  - Oxidation of lipoproteins is believed to play a key role in atherogenesis. In
      this study, influence of two fat vehicles, corn oil (unsaturated) or beef tallow
      (saturated), on cholesterol induced effects in terms of a) plasma lipoprotein
      peroxidation and b) aortic accumulation of cholesterol, cholesterol oxide and
      malonaldehyde was investigated in weanling rabbits. Although the increase in
      plasma cholesterol induced by cholesterol feeding was similar in both the groups
      Cu2+ ion induced peroxidation of lipoprotein cholesterol to oxysterols was
      significantly higher in corn oil group. This difference persisted even at 5 weeks
      after switching to chow diet. Aortic content of cholesterol and cholesterol
      oxides was also significantly higher in corn oil group at the end of chow diet
      period. Aortic accumulation of malonaldehyde (detected by immunocytochemistry)
      appeared to be greater in corn oil group at the end of the study. These results
      suggest that fatty acid composition of a given diet during exposure to high
      dietary cholesterol can influence cholesterol peroxidation to oxysterols and its
      accumulation in aorta.

PMID- 8300336
TI  - Nutritive value of four wild leafy vegetables in Cote d'Ivoire.
AB  - The overall composition, vitamin, carotene and mineral contents of the leaves of
      four wild plants (Ceiba pentandra, Grewia carpinifolia, Hibiscus congestiflorus,
      Triplochiton scleroxylon) used as vegetables in the traditional cuisine in Cote
      d'Ivoire were determined. The results are within the range of data published for
      domesticated leafy vegetables. The leaves revealed to be good sources of iron and
      calcium. Special attention is drawn to their contents of mucilages.

PMID- 8300337
TI  - No evidence of deficiency of vitamins A, E, beta-carotene, B1, B2, B6, B12 and
      folate in neuropathic type II diabetic women.

PMID- 8300338
TI  - Modulation of Graves' orbital fibroblast proliferation by cytokines and
      glucocorticoid receptor agonists.
AB  - PURPOSE: Paracrine/autocrine interactions between orbital fibroblasts (OF) and
      infiltrating lymphocytes/macrophages are thought to play a central role in the
      evolution of Graves' ophthalmopathy (GO). Compounds capable of stimulating the
      proliferation and synthetic capacities of OF may be of particular importance to
      these processes, because fibroblasts are known to both produce and respond to
      certain paracrine factors. METHODS: The effects of interleukin-1 alpha,
      interleukin-2, interleukin-4, interleukin-6, insulin-like growth factor I,
      transforming growth factor beta, and platelet-derived growth factor on OF
      monolayers derived from orbital fatty connective tissue and extraocular muscle
      endomysium of patients with severe GO undergoing orbital decompression (n = 3),
      and from connective tissue of normal persons (n = 3) were investigated.
      Stimulation of proliferation in growth-arrested OF was determined using
      immunocytochemical staining for the cell-proliferation-related nuclear antigen
      recognized by a monoclonal anti-Ki 67 antibody. In addition, the effects of OF
      coincubation with one of the aforementioned compounds and hydrocortisone (10(-7)
      M), the selective glucocorticoid receptor agonist RU 28362 (10(-7) M), or the
      glucocorticoid receptor antagonist RU 38486 (10(-7) M) were assessed. RESULTS:
      Under baseline conditions (0.1% fetal bovine serum), the proportion of
      proliferating cells was significantly higher in GO-OF compared with normal OF (p
      < 0.001). Significant stimulation of GO-OF proliferation was observed with
      interleukin-1 alpha (10 U/ml), interleukin-4 (1 ng/ml), insulin-like growth
      factor I (10 ng/ml), transforming growth factor beta (10 ng/ml), platelet-derived
      growth factor (1 ng/ml), and 1% or 15% fetal bovine serum (all P < 0.01), but not
      with interleukin-2 (10 U/ml) and interleukin-6 (100 U/ml). Compared with GO-OF,
      proliferation of normal OF was stimulated by fetal bovine serum to a similar
      degree, by interleukin-4, insulin-like growth factor I, transforming growth
      factor beta, and platelet-derived growth factor to a significantly lesser degree
      (all P < 0.01), and was unaffected by interleukin-1 alpha, interleukin-2, and
      interleukin-6. Compared with normal OF, either glucocorticoid receptor agonists,
      but not testosterone or progesterone, specifically inhibited the cytokine
      stimulated proliferation of GO-OF to a significantly greater degree (P < 0.01).
      CONCLUSIONS: The enhanced proliferative capacity of GO-OF at baseline and in
      response to certain cytokines could play a role in the evolution of the clinical
      manifestations in GO. Inhibition of cytokine-activated cellular functions may be
      one mechanism by which glucocorticosteroids exert clinically useful effects in
      GO.

PMID- 8300339
TI  - Effects of insulin and EGF on DNA synthesis in bovine endothelial cultures: flow
      cytometric analysis.
AB  - PURPOSE: To investigate the effects of insulin, epidermal growth factor (EGF),
      and the corneal storage media--DexSol--at 24 and 48 hours on DNA synthesis in
      confluent primary cultures of bovine corneal endothelial cells. METHODS: Flow
      cytometry was used to measure changes in DNA synthesis. This technique allows a
      large number of cells to be counted and sorted into G1, S, and G2/M phases of the
      cell cycle. RESULTS: Changing the normal culture media to DexSol had no effect on
      the cell cycle at 24 or 48 hours. The addition of insulin, EGF, or insulin + EGF
      to DexSol increased DNA synthesis within 24 hours. The mitotic indices for
      DexSol, DexSol + insulin, and DexSol + EGF were 0.134 (SE = +/- 0.022), 0.207 (+/
      0.027), and 0.205 (+/- 0.052), respectively. Adding insulin + EGF to the DexSol
      resulted in the most significant change in S and G2/M, increasing the mitotic
      index to 0.300 (+/- 0.072) (P = 0.0116). At 48 hours, the presence of the growth
      factors no longer had any effect. CONCLUSIONS: Flow cytometry was a useful
      technique in separating cultured bovine corneal endothelial cells according to
      their DNA content. Analysis of the cultures after the addition of insulin and EGF
      showed an increase in DNA synthesis. The synergistic effects of the growth
      factors on corneal endothelial cells suggest that they stimulate mitotic activity
      by different mechanisms. The addition of mitogens to eye bank storage media may
      increase corneal endothelial cell densities in donor corneas.

PMID- 8300340
TI  - Endothelin-mediated cell signaling and proliferation in cultured rabbit corneal
      epithelial cells.
AB  - PURPOSE: To determine if there is endothelin-mediated regulation of cell
      signaling and proliferation in rabbit corneal epithelium. METHODS: Endothelin-1
      (ET-1) gene and protein expression by the rabbit corneal epithelial (RCE) cells
      were analyzed by polymerase chain reaction, sequence analysis, and enzyme
      immunoassay. DNA synthesis was characterized by [3H]-thymidine uptake. Endothelin
      receptor linkage to cell signaling pathways was determined based on measurements
      of the dose dependent effects of ET-1, ET-2, and ET-3 on intracellular Ca2+
      concentration ([Ca2+]i) transients in fura-2-loaded cells, and of ET-1 on
      phosphoinositide turnover and cAMP accumulation in the isolated rabbit corneal
      epithelium. RESULTS: The authors detected the mRNA for prepro ET-1 in RCE cells,
      and ET-like immunoreactivity was identified in conditioned culture medium. ET-1
      (1 nM) maximally stimulated [3H]-thymidine uptake by twofold (EC50 = 0.3 nM).
      Endothelins elicited transient increases in [Ca2+]i with a rank order of potency
      of ET-1 > or = ET-2 >> ET-3. These increases consisted of both intracellular Ca2+
      mobilization and influx of Ca2+ from the bathing solution. Intracellular
      mobilization was linked to increases in IP3 turnover because 1 microM ET-1
      increased IP3 content by 48% from its control value (EC50 = 23 nM), whereas Ca2+
      influx occurred through a non-L-type Ca2+ channel because preexposure to 1 microM
      nicardipine did not affect either the height or the duration of a [Ca2+]i
      transient. One micromolar of ET-1 was required to elicit a significant increase
      in cAMP accumulation of 69% from its control value. This increase was dependent
      on the presence of Ca2+ in the bathing solution and was comparable to and
      nonadditive with that of the Ca2+ ionophore, A23187 (1 microM). CONCLUSION: These
      data suggest that endothelin production by primary cultures of RCE cells can
      mediate an increase in cell proliferation through an ETA receptor subtype. This
      receptor subtype appears to be involved based on the rank order of potency of ETs
      to elicit [Ca2+]i transients, increases in phosphoinositide turnover, and cAMP
      accumulation.

PMID- 8300341
TI  - Elevation of transforming growth factor alpha in cat aqueous humor after corneal
      endothelial injury.
AB  - PURPOSE: To determine if a scrape injury to cat corneal endothelial cells
      increases the level of mitogenic proteins such as transforming growth factor
      alpha (TGF alpha) in aqueous humor. METHODS: Aqueous humor of cats was collected
      at 0, 2, 6, and 24 hours after wounding the endothelium by contact with a cannula
      tip. Aqueous humor samples collected from sham-wounded cats served as controls.
      Aqueous humor samples were analyzed for levels of protein, for mitogenic activity
      using incorporation of tritiated thymidine by cultures of bovine corneal
      endothelial cells, and for immunoreactive TGF alpha protein using a specific
      radioimmunoassay. RESULTS: The average protein level in aqueous humor obtained
      before wounding was low (0.5 mg/ml), increased 26-fold at 2 hours after injury
      (13 mg/ml), then progressively decreased at 6 hours (8 mg/ml) and 24 hours (2
      mg/ml). Levels of mitogenic activity of aqueous humor samples collected 2, 6, and
      24 hours after wounding were 2-fold, 2.5-fold, and 0.6-fold higher, respectively,
      compared to the level of mitogenic activity measured in aqueous humor collected
      before wounding (0 hours) or in aqueous humor collected from sham-wounded eyes.
      TGF alpha concentration in aqueous humor collected before endothelial wounding
      was low (6.8 ng/ml), increased 14-fold 2 hours after wounding (97.4 ng/ml), then
      progressively decreased at 6 hours (63.3 ng/ml) and 24 hours (35.5 ng/ml) after
      wounding. TGF alpha concentrations in aqueous humor collected from sham-wounded
      eyes at 2 hours (9.5 ng/ml) and 6 hours (5.3 ng/ml) were not significantly
      different from prewound levels. Detergent extracts of bovine corneal endothelial
      cells contained substantial levels of TGF alpha immunoreactive protein (20 ng/mg
      protein). CONCLUSIONS: Wounding of cat endothelium causes a rapid increase in
      mitogenic proteins in aqueous humor including TGF alpha, which may act by an
      autocrine mechanism to stimulate endothelial wound healing.

PMID- 8300342
TI  - Effects of platelet-derived growth factor on endothelial wound healing of human
      corneas.
AB  - PURPOSE: To investigate the effects of platelet-derived growth factor (PDGF) on
      endothelial wound healing of organ-cultured human corneas. METHODS: The
      endothelia of paired human donor corneas (age, 71 +/- 11 years; total 84 pairs)
      were mechanically wounded (area, 5.6 +/- 0.8 mm2). Of each pair, one cornea was
      treated with 10 ng/ml human recombinant PDGF-BB while its mate served as control.
      The endothelial wound closure time was assessed by daily staining of the corneas
      with trypan blue. Morphometric data (endothelial cell density, shape, coefficient
      of variations) were obtained in the wound area after alizarin red staining. DNA
      synthesis was assessed using 3H-thymidine autoradiography. RESULTS: Although
      significant, the time of complete wound closure shortened only marginally on
      addition of PDGF to the culture medium. In the closed wound center (between 4 and
      9 days), all corneas exposed to PDGF had significantly higher endothelial cell
      densities (737 +/- 126 cells/mm2) than the control corneas (515 +/- 89
      cells/mm2). Fifteen days after wounding, the mean endothelial cell density
      averaged 526 +/- 93 and 708 +/- 135 cells/mm2 in the control and PDGF-treated
      groups, respectively. PDGF did not affect the final cell shape within the closed
      wounds. DNA synthesis was significantly but only marginally enhanced in PDGF
      treated corneas. CONCLUSION: In organ-cultured human corneas, PDGF-BB promotes
      endothelial wound healing predominantly by cell migration, at least in corneas
      from senior donors.

PMID- 8300343
TI  - A primary role for RPE transplants in the inhibition and regression of
      neovascularization in the RCS rat.
AB  - PURPOSE: Healthy retinal pigment epithelial (RPE) cell transplants in retinas of
      postnatal day 27 Royal College of Surgeons (RCS) rat are capable of preventing
      photoreceptor cell degeneration, inhibiting the degeneration of the retinal
      vascular bed and the subsequent neovascularization of the RPE that occurs in
      retinas injected with saline. In the present study, the authors have tested the
      hypothesis that RPE transplants might also prevent vascularization of the RPE
      layer in RCS retinas when photoreceptor cells either had just degenerated or, at
      3 months, disappeared. METHOD: Retinas of 3- and 6 month-old RCS rats were
      injected with either healthy neonatal RPE cells or vehicle and were examined at 6
      and 8 months, respectively. These retinas were studied using horseradish
      peroxidase visualization of the vasculature in retinal wholemount preparations
      and by light microscopy. RESULTS: The number of neovascular profiles in
      wholemount preparations of RCS retinas that had received healthy RPE transplants
      at 3 months and were analyzed at 6 months were significantly decreased when
      compared to sham-injected retinas of age-matched RCS rats, 2.09 +/- 0.94 and
      15.28 +/- 1.34 profiles per mm2, respectively (P < 0.001). In addition, when
      comparing retinas transplanted or sham injected at 6 months and examined at 8
      months, significantly fewer neovascular profiles were found in the transplant
      group, 9.32 +/- 1.02 and 15.42 +/- 0.84 profiles per mm2, respectively (P <
      0.002). CONCLUSION: These data provide still further evidence for the role of
      healthy RPE in maintaining the homeostasis of the normal retinal vasculature in
      the retina of the RCS rat. The relationships between the RPE and the retinal
      vasculature are important when considering that alterations in the
      vascularization of the retina play a major role in some of the most sight
      debilitating diseases, such as the wet form of age-related macular degeneration
      and proliferative diabetic retinopathy.

PMID- 8300344
TI  - Characterization of glucose transporter in cultured human retinal pigment
      epithelial cells: gene expression and effect of growth factors.
AB  - PURPOSE: To investigate gene and protein expression of glucose transporter
      isoforms in cultured human retinal pigment epithelial cells. To investigate
      growth factor-dependent stimulation of glucose transport and the effect of growth
      factors on the gene and protein expression in retinal pigment epithelial cells.
      METHODS: Glucose transport activity was analyzed by [3H]2-deoxyglucose uptake
      studies. Gene and protein expression of glucose transporter isoforms were
      analyzed by polymerase chain reaction, Northern blot analysis, and Western blot
      analysis. RESULTS: Polymerase chain reaction, nucleotide sequencing, and Southern
      blot analyses revealed that the retinal pigment epithelial cells express GLUT-1, 
      3, and -5 genes. Northern and Western blot analysis detected only GLUT-1
      transcripts and protein. A 24-hour exposure to fetal bovine serum (15%), basic
      fibroblast growth factor (50 ng/ml), platelet-derived growth factor (10 ng/ml),
      epidermal growth factor (50 ng/ml), and insulin-like growth factor-1 (50 ng/ml)
      significantly stimulated [3H]2-deoxyglucose uptake in cultured human retinal
      pigment epithelial cells. Western blot analysis showed that serum and platelet
      derived growth factor induced an increase of GLUT-1 protein in the membrane
      preparation in the cells. Serum, fibroblast growth factor, platelet-derived
      growth factor, and insulin-like growth factor-1 did not increase GLUT-1 gene
      expression to an appreciable level, as shown by Northern blot analysis.
      CONCLUSION: Cultured human retinal pigment epithelial cells dominantly express
      GLUT-1 gene and protein with minor expression of GLUT-3 and -5 genes. Fetal
      bovine serum, fibroblast growth factor, platelet-derived growth factor, epidermal
      growth factor, and insulin-like growth factor-1 significantly, although modestly,
      increase glucose transport activity of the cells.

PMID- 8300345
TI  - Suppression of cAMP-induced pigment granule aggregation in RPE by organic anion
      transport inhibitors.
AB  - PURPOSE: To investigate the mechanism(s) by which intracellular cAMP levels are
      elevated to induce pigment granule aggregation in teleost retinal pigment
      epithelium (RPE). METHODS: Pigment granule migration was studied in vitro using
      RPE sheets isolated from dark-adapted green sunfish, Lepomis cyanellus. After
      preculture to allow pigment granule dispersion, RPE sheets were incubated with
      various agents to test their ability to induce pigment granule aggregation. RPE
      sheets were then fixed, and pigment granule position was assessed
      microscopically. RESULTS: Pigment granule aggregation was induced by
      nonderivatized cAMP. At maximally effective concentration (1 mM), cAMP was as
      effective as its more membrane-permeant analogs dbcAMP and 8-Br-cAMP. Forskolin
      (1 or 10 microM), a stimulator of adenylyl cyclase, was also effective at
      inducing pigment aggregation. Two inhibitors of organic anion transport,
      probenecid and sulfinpyrazone, inhibited cAMP-induced aggregation by
      approximately 80% but had no effect on forskolin-induced aggregation. Several
      agents shown to stimulate RPE adenylyl cyclase in other species failed to induce
      pigment aggregation in isolated RPE sheets. CONCLUSIONS: Our observations
      strongly suggest that exogenously applied, nonderivatized cAMP can gain access to
      the cytoplasm of isolated RPE cells via organic anion transporters. Thus, if cAMP
      were secreted by retinal cells into the subretinal space, it could be taken up by
      RPE cells and subsequently act as an intracellular messenger to activate dark
      adaptive physiological processes such as pigment granule aggregation.

PMID- 8300346
TI  - Characterization of monoclonal antibodies recognizing retinal pigment epithelial
      antigens.
AB  - PURPOSE: To purify and characterize retinal pigment epithelial proteins
      exhibiting uveitogenic characteristics after immunization of Lewis rats, a broad
      panel of monoclonal antibodies directed against retinal pigment epithelial (RPE)
      protein antigens, was isolated. METHODS: Bovine RPE detergent extracts were used
      to isolate monoclonal antibodies against RPE antigens. Species and tissue
      specificity within the eye was tested through immunocytochemical analysis.
      Western blot analysis was used to determine the molecular weight of the RPE
      antigens. RESULTS: Several RPE-reactive antibodies were obtained. At least four
      monoclonal antibodies were isolated that reacted with different RPE antigen
      types. Against most of the antigens more than one hybridoma cell line was
      isolated. Two hybridoma lines were isolated producing antibodies, which on
      immunocytochemical analysis showed strong reactivity with the RPE and eye muscle
      tissue. The latter monoclonal antibody recognizes a 32 kD protein in RPE cells.
      Five monoclonal antibodies recognize a protein with an apparent molecular weight
      of 65 kD. One cell line was isolated that produced antibodies showing an
      irregular reaction pattern with both iris and ciliary body. CONCLUSIONS: RPE
      cells, striated eye muscle and smooth muscle cells share a 32 kD antigenic
      protein. This antigen is present in almost all ocular epithelial cells. Based on
      reaction patterns on Western blot and immunocytochemical analysis, there are at
      least three different 65 kD RPE antigens, two of which are RPE-specific and one
      of which is also present in the kidney epithelium.

PMID- 8300347
TI  - Heterogeneity in ultrastructure and elemental composition of perinuclear lens
      retrodots.
AB  - PURPOSE: To unravel the cataractogenic process(es) leading to the birefringent
      lenticular bodies known as perinuclear retrodots. METHODS: Ten human lenses
      containing biomicroscopically verified perinuclear retrodots were systematically
      screened and analyzed using scanning electron microscopy and energy dispersive x
      ray microanalysis to verify their ultrastructure and elemental composition.
      RESULTS: Three types of retrodots were distinguished, different in size,
      ultrastructure, and origin. Two of them contained calcium phosphate, the third
      probably contained calcium oxalate. All three types were separated from
      surrounding normal fibers and the crystalline inclusions were sequestered within
      membrane-lined bodies. CONCLUSIONS: Because of these observations and data found
      in the literature it is postulated that elevated free calcium is the initiating
      factor in the formation of retrodots, trapped by either oxalate or phosphate and
      sequestered in the retrodots. It is suggested that the oxalate is derived from
      ascorbate because of impaired protection against oxidative stress in the older
      lens. Phosphoric acid is believed to be released by calcium-induced hydrolysis of
      membrane phospholipids.

PMID- 8300348
TI  - 1193 Association for Research in Vision and Ophthalmology questionnaire results.

PMID- 8300349
TI  - Cell-to-cell communication in a differentiating ovine lens culture system.
AB  - PURPOSE: This study was performed to determine whether the junctions between both
      the epithelial and the differentiating fiber-like cells of ovine lens cultures,
      like gap junctions in other tissues, exhibit cell-to-cell communication that is
      inhibited by n-octanol, and to determine whether lens connexins and the fiber
      cell membrane proteins MP20 and MP26 are expressed by these ovine lens cell
      cultures. METHODS: Cells were injected with Lucifer yellow CH to measure cell-to
      cell communication. Antibodies to connexin-related lens membrane protein MP70,
      connexin 43 (Cx43), and connexin 46 (Cx46) and to membrane proteins MP20 and MP26
      were used to immunofluorescently label lens cultures and probe Western blots of
      membranes isolated from lens cultures. RESULTS: Both epithelial cells and
      differentiating clear cells exhibited cell-to-cell transfer of Lucifer yellow
      that was inhibited by n-octanol. Although a Cx43 antibody immunofluorescently
      labeled small plaques between the epithelial cells, an MP70 antibody labeled
      large plaques as well as small punctate areas of the differentiating fiber-like
      cells. It is interesting that Cx43 and MP70 were frequently present in the same
      plaques at cell interfaces between epithelial cells as well as some of the larger
      plaques on the differentiating fiber-like cells. Cx46 and MP70 antibodies labeled
      the same plaques in membranes of differentiating fiber-like cells and late-stage
      epithelial cells. The electrophoretic mobility of all three connexin proteins was
      modified after treatment with alkaline phosphatase. Immunohistochemical staining
      of these differentiating regions and Western immunoblotting of purified membranes
      derived from differentiated cultures also showed the presence of MP20 and MP26.
      CONCLUSIONS: The different cell types in the ovine lens culture exhibit gap
      junction-mediated cell-to-cell communication that is likely effected by one or
      more of the connexin proteins.

PMID- 8300350
TI  - Corneal nerve damage and regeneration after excimer laser photokeratectomy in
      rabbit eyes.
AB  - PURPOSE: To investigate corneal nerve damage and its subsequent regeneration
      after excimer laser photokeratectomy in rabbit eyes. METHODS: Corneal
      photokeratectomy was performed on the right eyes of 34 pigmented rabbits, while
      the left eyes were used as a control. A Summit UV 200 excimer laser (Summit
      Technology, Waltham, MA) was used to produce a 100 microns depth phototherapeutic
      keratectomy (4.5 mm diameter). The rabbits were killed at 0, 1, 2, 3, 4, 5, 7, 8,
      10, 15, and 20 days and 1, 2, 3, and 4 months after treatment. Corneal nerve
      regeneration was investigated using a monoclonal antibody directed against a 150
      kD subunit of neurofilaments, in combination with acetylcholinesterase staining.
      RESULTS: At time 0, the subepithelial plexus had disappeared completely from the
      photoablated area. One day after treatment, some regenerating nerves sprouting
      within the treated area were visualized by a monoclonal antibody directed against
      a 150 kD subunit of neurofilaments. Acetylcholinesterase staining was detectable
      7 days later. One month after surgery the subepithelial plexus had already
      reappeared, but was morphologically disorganized. Four months after treatment,
      the newly formed subepithelial plexus had considerably thickened in comparison
      with that of the control eye. CONCLUSIONS: This study shows that corneal nerve
      regeneration after excimer laser photoablation in rabbit eyes, although more
      intense, is similar to that produced after other surgical procedures involving
      the epithelium and the anterior stroma or one of the two.

PMID- 8300351
TI  - Human corneal extract enhances serum complement activity.
AB  - PURPOSE: The concomitant presence of complement-activation products in the cornea
      during inflammation is well described. The present study was undertaken to
      analyze the complement activity of normal human corneal tissue and to assess the
      presence of complement-modulating activities. METHODS: Human corneal tissue was
      extracted in veronal-buffered saline. The overall complement (C) activity of the
      human corneal extract (HCE) and the effect of HCE on serum C-activity were
      investigated using a hemolytic assay. Anion-exchange chromatography and gel
      filtration were applied for biochemical analysis of HCE. Monoclonal anti-human C3
      was used to detect corneal C3 and to remove C3 from HCE by immunoadsorption.
      RESULTS: It was found that C-activity of HCE was less than 200 U/g tissue.
      Experiments to test whether HCE exhibited inhibitory activity led to an
      unexpected result: When added to human serum dilutions, HCE caused a significant,
      dose-dependent increase of C-activity. Pretreatment of HCE at 56 degrees C
      abolished the effect. Analysis of HCE by anion-exchange chromatography revealed
      two C-enhancing peaks. One peak was identified as C3 whereas the identity of the
      other protein peak remained unknown. CONCLUSIONS: Results indicate that the human
      cornea contains an as yet unidentified heat sensitive factor(s) able to enhance
      complement activity of serum. It is postulated that this factor(s) may play an
      important role in corneal physiology and pathology.

PMID- 8300352
TI  - Induction of c-fos by prostaglandin F2 alpha in human ciliary smooth muscle
      cells.
AB  - PURPOSE: To evaluate the induction of the proto-oncogene c-fos in cultured human
      ciliary muscle cells by prostaglandin F2 alpha (PGF2 alpha) by 17-phenyltrinor
      PGF 2 alpha. METHOD: Human ciliary muscle cells were grown to confluency in
      monolayer cell culture, placed in medium containing 1% fetal bovine serum for 5
      days, treated by addition of PGF2 alpha or the trinor derivative, fixed, and then
      immunocytochemically stained using an antibody to c-Fos, the protein product of
      the translation of c-fos. RESULTS: After treatment with either agonist, the mean
      induction score (proportion of brightly immunostained nuclei) increased to a
      maximal level during the first hour and returned to basal levels 4 to 8 hours
      after treatment. Increasing the agonist concentration increased the maximal
      level, but had no effect on the time course of the response. The dose responses
      after 1 hour of treatment with PGF2 alpha or 17-phenyltrinor-PGF2 alpha increased
      similarly between 1.6 x 10(-9) M and 2 x 10(-7) M. When treated with 1 x 10(-6) M
      of either agonist, however, the induction was half that obtained at 2 x 10(-7) M.
      CONCLUSION: Exposure of ciliary smooth muscle cells to either PGF2 alpha or 17
      phenyltrinor-PGF2 alpha induces an immediate early gene expression response that
      is similar to c-Fos induction in other cell systems. These results establish the
      basis for future investigations evaluating the potential role of c-fos induction
      in mediating the effects of PGF2 alpha on uveoscleral outflow.

PMID- 8300353
TI  - Lysosomal enzyme and inhibitor levels in the human trabecular meshwork.
AB  - PURPOSE: To examine in the human trabecular meshwork lysosomal enzymes and one
      inhibitor of serine proteases that actively participate in the degradation of
      macromolecules into low molecular weight constituents. METHODS: Using an avidin
      biotin-peroxidase technique, lysosomal proteases and alpha 1-proteinase inhibitor
      were examined in the trabecular meshwork of 23 human eyes with donor ages ranging
      from 2 to 90 years. These eyes were categorized into three age groups (< or = 20,
      21 to 49, and > or = 50 years). Histochemical staining for lysosomal hydrolases
      was also performed on frozen sections of 20 human eyes. The staining was analyzed
      by an image analyzer and the levels of lysosomal proteases were further measured
      by biochemical assays. RESULTS: The trabecular meshwork from all the eyes stained
      intensely against antibodies to cathepsins B and G and alpha 1-proteinase
      inhibitor. The staining for elastase was weaker but evident. Image analyses
      revealed that the staining intensity for each protease or inhibitor was similar
      in all age groups. The staining in the uveal meshwork appeared to be the
      strongest among all the trabecular meshwork regions. Biochemical assays of tissue
      extracts confirmed that the enzyme and inhibitor levels were comparable among the
      three donor age groups. Activities of two lysosomal hydrolases, acid phosphatase
      and acid esterase, were also found in trabecular meshwork cells of 20 eyes. No
      apparent difference in enzyme activities was found with increasing age, and
      variation related to region was not observed. CONCLUSIONS: This study
      demonstrated the age-independent distribution of a variety of lysosomal enzymes
      and a protease inhibitor in the human trabecular meshwork. The presence of these
      proteins suggests a possible role in the metabolic operation of the trabecular
      meshwork.

PMID- 8300354
TI  - Influence of type and severity of pure forms of age-related cataract on visual
      acuity and contrast sensitivity. Italian American Cataract Study Group.
AB  - PURPOSE: To compare the relationship between logMAR visual acuity (VA) and
      cataract severity and between contrast sensitivity (CS) and cataract severity in
      pure types of age-related lens opacities. METHODS: Analysis included patients
      followed in the ongoing Italian-American Study of the Natural History of Age
      Related Cataract. Lens opacities were classified and graded according to the Lens
      Opacities Classification System II (LOCS II). Visual acuity was measured with the
      Early Treatment Diabetic Retinopathy Study Chart. Contrast sensitivity was
      measured with the Pelli-Robson chart. RESULTS: Data from 1,076 eyes were used for
      the analysis (366 clear lenses; 550, 124, and 36 eyes with cortical, nuclear and
      posterior subcapsular cataract, respectively). In age-adjusted analyses,
      increasing severity of all three cataract types was associated with progressively
      higher logMAR VA, which translates into poorer acuity, and lower CS scores. For
      both VA and CS, the effect of increasing severity was greatest for nuclear and
      least for cortical opacities. After adjusting for age and VA, CS scores were no
      longer associated with cataract type and severity, with the exception of advanced
      cortical opacities. CONCLUSIONS: Increased cataract severity, as determined by
      LOCS II grading, is strongly associated with both VA and CS scores. Contrast
      sensitivity scores obtained from testing at low spatial frequency do not seem to
      offer additional information over standard VA testing in early cortical and
      posterior subcapsular opacities nor in nuclear cataracts.

PMID- 8300355
TI  - Fatigue effects during a single session of automated static threshold perimetry.
AB  - PURPOSE: To determine using a routine clinical program the time course of the
      fatigue effect in both eyes at a given examination, the influence of rest periods
      during the examination, and the differences in the fatigue effect between persons
      with ocular hypertension and age-matched normal subjects. METHODS: Perimetry was
      undertaken for both eyes of 20 normal persons and 20 persons with ocular
      hypertension using Program G1X (Interzeag AG, Schlieren, Switzerland) of the
      Octopus 1-2-3 perimeter. Global mean defect and loss variance were calculated for
      each of the eight individual stages and global SF was calculated for stages 5 to
      8. The superoinferior and nasotemporal hemifield indices and those for within and
      beyond 17 degrees eccentricity were calculated separately to investigate the
      locus of the fatigue effect. RESULTS: Group mean mean defect and loss variance
      deteriorated over stages (P < 0.001) and between eyes for both groups (P < 0.001;
      P < 0.004). The deterioration in the mean defect was more marked peripherally (P
      < 0.001) and inferiorly with age and group (P < 0.001) whereas the localized loss
      was more pronounced peripherally (P < 0.001), superiorly (P < 0.010) and nasally
      (P < 0.001). A 1-minute break during the examination of a given eye and a 3
      minute break between eyes was insufficient to overcome the fatigue effect. The
      performance of the two groups was almost indistinguishable. CONCLUSIONS: The
      deterioration in the visual field indices mean defect and loss variance
      challenges the currently accepted ideal length of a perimetric examination with
      the conventional algorithms. Confidence limits for the definition of abnormality
      with these algorithms should reflect the presence of the fatigue effect and be
      different for the second eye.

PMID- 8300356
TI  - Glucocorticoid-induced formation of cross-linked actin networks in cultured human
      trabecular meshwork cells.
AB  - PURPOSE: To determine the effects of glucocorticoid treatment on the
      microfilament structure of cultured human trabecular meshwork cells. Topical or
      systemic administration of glucocorticoids can lead to the development of ocular
      hypertension and to the development of vision loss, which is clinically similar
      to primary open angle glaucoma. However, the mechanism(s) by which
      glucocorticoids cause ocular hypertension is not well defined. Alterations in the
      trabecular meshwork, the site of drainage of aqueous humor from the eye, have
      been linked to the development of ocular hypertension. METHODS: Human trabecular
      meshwork cells were cultured in the presence and absence of glucocorticoids for 0
      to 21 days. The microfilament organization of the cultured trabecular meshwork
      cells was examined by epifluorescent and transmission electron microscopy.
      RESULTS: Glucocorticoids caused a progressive change in the organization of
      microfilaments in the trabecular meshwork cells, but not in other cultured ocular
      cells. By fluorescence microscopic analysis, the actin stress fibers found in
      control trabecular meshwork cells were reorganized on treatment with
      glucocorticoids into cross-linked actin networks that resembled geodesic-dome
      like polygonal lattices. The cross-linked actin networks were reversible on
      withdrawal of the glucocorticoid treatment. Dose-response data for dexamethasone,
      relative ranking of activity with glucocorticoid potency, and partial inhibition
      with glucocorticoid antagonists all suggest the involvement of the trabecular
      meshwork glucocorticoid receptor in cross-linked actin network formation. The
      reorganization of the trabecular meshwork cytoskeleton alters cell function
      because glucocorticoid treatment of cultured trabecular meshwork cells also
      inhibited trabecular meshwork cell migration and proliferation. CONCLUSION: The
      steroid-induced alteration in trabecular meshwork cytoskeleton may be an
      important factor in the development of steroid-induced ocular hypertension and
      may play a role in the ocular hypertension associated with primary open angle
      glaucoma.

PMID- 8300357
TI  - Analysis of ERG a-wave amplification and kinetics in terms of the G-protein
      cascade of phototransduction.
AB  - PURPOSE: To test rigorously the hypothesis that the a-wave of the
      electroretinogram (ERG) is proportional to the rod photocurrent by examining the
      applicability to a-waves of a recent model of the activation steps in the G
      protein cascade of phototransduction. METHODS: ERGs were recorded in response to
      flashes of graded intensity, from six dark-adapted normal subjects and from two
      patients, one with retinitis pigmentosa (RP) and one with cone retinal dystrophy
      with rod involvement (CRD). The a-wave portions of the responses were analyzed
      with a model of the activation steps of the G-protein cascade. The model is
      characterized by a parameter, A, the amplification constant, with units of s-2
      (per photoisomerization), which may be expressed as the product of physical and
      biochemical parameters of the transduction cascade. RESULTS: Each a-wave family
      was well described by the model. For the six normal subjects, we obtained A
      approximately 7 s-2, about 100-fold greater than in isolated amphibian rods at 22
      degrees C, but close to the value for isolated primate rods. For the patient with
      RP, the maximum a-wave amplitude (amax) was considerably reduced, but the
      amplification constant was normal (A = 7.5 s-2). In contrast, the patient with
      CRD had a nearly normal amax but had an amplification constant about sixfold
      lower than normal (A = 1.1 s-2). CONCLUSIONS: The authors conclude that the a
      wave is a direct reflection of the rod photo-current and that the rising phase
      kinetics are accurately described by a simple model of the G-protein cascade.
      They show that the small volume of the human rod outer segment is crucial to the
      achievement of high amplification, and they show how their observations constrain
      the possible pathologies of phototransduction in patients with retinal disease.

PMID- 8300358
TI  - Corneal edema recovery dynamics in diabetes: is the alloxan induced diabetic
      rabbit a useful model?
AB  - PURPOSE: To compare the contact lens-induced corneal edema recovery dynamics of
      human subjects with type 1 diabetes with those of age- and sex-matched normal
      human subjects; to compare the human data with previously reported data from
      alloxan-induced diabetic rabbit. METHODS: Corneal edema was induced by 2 hours of
      closed eye wear with a thick, soft contact lens. After removal of the contact
      lens, central corneal thickness measurements were made at 30-minute intervals for
      3 hours using optical pachometry. RESULTS: Human subjects with type 1 diabetes
      demonstrated a significantly slower rate of corneal edema recovery than age- and
      sex-matched human controls. The rate of corneal edema recovery found in this
      study for human subjects with type 1 diabetes is similar to that previously
      reported for alloxan-induced diabetic rabbits. CONCLUSIONS: The decreased corneal
      edema recovery ability of the patient with type 1 diabetes suggests that care
      should be taken when prescribing contact lens use in these people. The similarity
      between corneal edema recovery rates in the human subject with type 1 diabetes
      and the alloxan-induced diabetic rabbit supports the use of the alloxan-induced
      diabetic rabbit as an animal model for studies of corneal edema recovery dynamics
      in diabetes.

PMID- 8300359
TI  - Interocular transfer of the movement aftereffect in central and peripheral vision
      of people with strabismus.
AB  - PURPOSE: To compare binocularity in central and peripheral vision of people with
      early-onset strabismus and people with normal binocular vision. METHODS: Ten
      subjects with early-onset strabismus, and nine subjects with normal binocular
      vision were tested. To assess binocularity, interocular transfer (IOT) of a
      rotary movement aftereffect (MAE) was measured. The MAE stimuli were either
      confined to the central 2.8 degrees of the visual field or were presented 10
      degrees into peripheral vision. RESULTS: In peripheral vision, there was no
      significant difference in IOT for the two groups of subjects. In central vision,
      there was a significant decrease of IOT in subjects with early-onset strabismus.
      Their IOT was, however, significantly greater than zero. CONCLUSIONS: Early-onset
      strabismus appears to spare binocularity in peripheral vision but reduces it in
      central vision. It does not abolish binocularity assessed by IOT of MAE,
      suggesting that some binocular connections survive early-onset strabismus, even
      in central vision.

PMID- 8300360
TI  - Confirmation of the validity of the psychophysical light scattering factor.
AB  - PURPOSE: To reevaluate the validity of the light scatter factor (LSF) formula of
      Paulsson and Sjostrand, LSF = L/E (M2/M1-1), where L is the target luminance, E
      is the illuminance of the glare source at the eye, and M2 and M1 are modulation
      contrast thresholds measured with and without the glare source, respectively.
      This equation has recently been deemed invalid by Yager, Yuan, and Mathews.
      METHOD: Ratios of contrast thresholds with and without glare were measured for
      three glare illuminance levels for each of three stimulus luminances. This
      results in five different ratios of L/E, spanning a range of 1.60 log units.
      RESULTS: The data show an excellent fit to the Paulsson and Sjostrand equation,
      and the LSF scores conform well to previously published normative values.
      CONCLUSION: The light scatter factor equation of Paulsson and Sjostrand is
      confirmed as valid without resorting to the need for correction factors based on
      variables such as pupil size.

PMID- 8300361
TI  - Dominance of activated T cells and interleukin-6 in aqueous humor in Vogt
      Koyanagi-Harada disease.
AB  - PURPOSE: To determine the immunopathologic role of the lymphocytes and
      lymphokines in aqueous humor (AH) of patients with Vogt-Koyanagi-Harada disease
      (VKH). METHODS: The distribution of leukocyte subsets in the peripheral blood and
      AH was examined using fluorescein isothiocyanate-conjugated monoclonal
      antibodies. The levels of lymphokines, such as interleukin-2 (IL-2) and
      interleukin-6 (IL-6), in the sera, AH, and cerebrospinal fluid from the patients
      with VKH were determined using an enzyme-linked immunosorbent assay. RESULTS: T
      cells constituted the majority of lymphocytes within AH. The value for CD4+ cells
      (helper/inducer T lymphocytes) in AH was 51.7% +/- 14.9% (mean +/- SD) and that
      for CD8+ cells (cytotoxic/suppressor T lymphocytes) was 31.1% +/- 13.0%. The
      percentage of HLA-DR+ cells (B lymphocytes, monocytes, macrophages, and activated
      T lymphocytes) in AH (50.8% +/- 24.9%) significantly exceeded (P < 0.001) that in
      blood (13.1% +/- 4.2%). The percentage of CD8+ cells in AH from three patients
      with the delayed type of VKH rose during their clinical course. The level of IL-6
      was significantly elevated in AH from the patients with VKH. The level of IL-6 in
      AH correlated with the number of lymphocytes in AH, and it reflected the severity
      of the inflammatory response in AH of patients with VKH. The level of IL-2 in the
      sera, AH, and cerebrospinal fluid was in the normal range. CONCLUSIONS: Aqueous
      humor lymphocytes from the patients with VKH were more activated than were
      peripheral blood lymphocytes. IL-6 may play an important role as an inflammatory
      mediator in VKH. It may be useful to analyze the lymphocyte subsets and the
      levels of lymphokines, especially of IL-6, at the site of inflammation in uvea to
      improve the criteria for assessing the prognosis of VKH.

PMID- 8300363
TI  - Tissue plasminogen activator activity in human aqueous humor.
AB  - PURPOSE: To determine the levels of free plasminogen activator activity in human
      aqueous humor and to identify the type of activity (i.e., tissue-type t-PA or
      urokinase-type u-PA) that is responsible. METHODS: Aqueous humor was obtained by
      a simplified pipette paracentesis before cataract surgery in 31 subjects, ages 57
      to 93 years. Levels of plasminogen activator activity were determined using a
      modified 17-hour specific amidolytic assay. The type of plasminogen activator was
      investigated in selected samples based on its dependence on soluble fibrin,
      inhibition by amiloride, and specific antibody blocking. Activity-antigen ratios
      were compared in seven samples. RESULTS: Plasminogen activator (PA) activity was
      present in all samples tested. PA activity ranged widely between 0.54 and 26.7
      mIU/ml, with a mean value of 10.8 +/- 8.1 mIU/ml. Soluble fibrin, a known
      stimulator of tissue-type plasminogen activator (t-PA), was required in the assay
      system. Its absence decreased the measured activity by more than 90%. Amiloride,
      a known inhibitor of urokinase-type PA, had little or no effect in selected
      samples tested. The activity was blocked by anti-human t-PA antibodies but not by
      antibodies against human u-PA, further defining the type of PA responsible for
      the detected activity. t-PA antigen levels showed less variation among
      individuals than did activity levels. Antigen-activity ratios ranged between 89
      and 552. CONCLUSION: Plasminogen activator activity is present in the human
      aqueous humor in measurable quantities. The type of PA activity present is almost
      exclusively t-PA. t-PA activity varies more widely than antigen, as is the case
      in plasma.

PMID- 8300362
TI  - Role of retinal pigment epithelium in the development of experimental autoimmune
      uveitis.
AB  - PURPOSE: To determine the role of retinal pigment epithelium in the induction of
      S-antigen-induced uveitis by administration of sodium iodate (NaIO3) to
      selectively damage the retinal pigment epithelium. METHODS: Forty-four Lewis rats
      were injected with 60 micrograms of S antigen in complete Freund's adjuvant. On
      postimmunization day 9 the rats were separated into four groups: three groups
      received NaIO3 at doses of 50, 25, and 10 mg/kg body weight, respectively, and
      the fourth group (control) received diluent. In addition, separate groups of
      animals (three in each group) received various doses of NaIO3 or diluent. All of
      the animals were killed on day 6 after NaIO3 injection, and the eyes were
      enucleated and submitted for light and electron microscopic examination. In
      addition, two groups of Lewis rats (6 in each group) were immunized with 0.5 ml
      of guinea pig spinal cord homogenate in complete Freund's adjuvant to induce
      experimental allergic encephalomyelitis. On postimmunization day 7, one group
      received NaIO3 at a dose of 50 mg/kg body weight, whereas the other group
      received diluent. All animals were killed between days 12 and 14, and spinal cord
      sections were obtained for microscopic examination. RESULTS: In the control group
      immunized with S antigen, severe (2+ to 4+) uveoretinitis developed in 70% of the
      animals. In contrast, only 18% of the animals injected with NaIO3 at a dose of 50
      mg/kg body weight exhibited disease, and this was a mild (1+) form. The groups
      injected with 25 mg/kg (1+ to 2+) and with 10 mg/kg (2+ to 3+) of NaIO3 showed a
      mild to moderate degree of uveoretinitis in 27% and 50% of the animals,
      respectively. In the remainder of the animals there was no evidence of
      uveoretinitis. All of the NaIO3-treated animals showed selective necrosis of the
      retinal pigment epithelium; this was extensive in the higher dose group and focal
      in the lower dose groups. In the experimental allergic encephalomyelitis model
      there was no significant difference in incidence or histologic appearance of
      demyelinating disease in NaIO3- vs diluent-treated groups. CONCLUSIONS: These
      results indicate that the retinal pigment epithelium may play a role in the
      initiation and perpetuation of uveitis after sensitization with S antigen. The
      effect of NaIO3 appears to be localized to the retinal pigment epithelium; it had
      no effect on immune reactive cells, as evidenced by the development of
      experimental allergic encephalomyelitis in animals treated with NaIO3.

PMID- 8300364
TI  - Introduction of King-Wai Yau 1993 Friedenwald Award winner.

PMID- 8300365
TI  - Localization and characterization of major histocompatibility complex class II
      positive cells in the posterior segment of the eye: implications for induction of
      autoimmune uveoretinitis.
AB  - PURPOSE: To identify potential antigen-presenting cells in the choroid and retina
      of the normal rat eye, with a view to proposing a role for such cells in the
      induction and perpetuation of experimental autoimmune uveoretinitis, a model of
      human uveoretinal inflammation. METHODS: Immunohistochemical and electron
      microscopic studies using a panel of monoclonal antibodies were performed on
      frozen sections of the perfused-fixed normal Lewis rat eye, choroid whole mounts,
      and cytospin preparations of cells harvested from choroid/ciliary body explant
      cultures. In addition, time-lapse video recordings of migratory uveal tract cells
      in culture were taken. RESULTS: No major histocompatibility complex class II
      positive cells were found in the normal Lewis rat retina. However, at least three
      populations of potential antigen-presenting cells were found in the uveal tissues
      of the eye: classical dendritic cells expressing high levels of major
      histocompatibility complex class II antigen; resident dendritiform macrophages,
      which were negative for major histocompatibility complex class II antigen, but
      expressed specific macrophage markers (ED2); and blood-borne macrophages (ED1)
      that had emigrated from the vasculature into the tissue compartment. In addition
      there were small numbers of cells expressing novel markers such as markers
      usually found only on macrophage subsets in splenic tissue (ED3) and a recently
      described marker for veiled dendritic cells (OX62). Dendritic cells and resident
      dendritiform macrophages closely interacted with each other and with tissue
      cells, particularly retinal pigment epithelial cells. CONCLUSIONS: The posterior
      uveal tract is richly populated with classical dendritic cells expressing
      constitutive high levels of major histocompatibility complex class II antigen.
      There are also several types of macrophages with the potential to modulate immune
      responses in the posterior segment. Interactions among these cells and with
      resident tissue cells such as retinal pigment epithelial cells are probably
      central to the initiation of (auto)immune responses in the posterior segment of
      the eye.

PMID- 8300366
TI  - Effect of dietary fish oil on acute light-induced photoreceptor damage in the rat
      retina.
AB  - PURPOSE: Previous studies have shown that ingestion of fish oil (FO) containing a
      high proportion of n-3 polyunsaturated fatty acids increases the susceptibility
      of cellular membranes to oxidative damage in various tissues. In the retina,
      lipid peroxidation is thought to be a major mechanism contributing to light
      induced lesions. Therefore, we investigated the effect of FO on acute light
      induced photoreceptor damage. METHODS: For 2 months, weanling rats were fed diets
      containing either soybean oil (SOY) or FO as main lipid component. RESULTS: Rats
      fed FO had significantly higher levels of eicosapentaenoic acid (EPA, 20:5n-3)
      and higher ratios of EPA to arachidonic acid (AA, 20:4n-6) in retinal
      phospholipids and diacylglycerols than rats fed SOY. The levels of
      docosahexaenoic acid (DHA, 22:6n-3) were similar in both dietary groups. The
      susceptibility to lipid peroxidation was enhanced in the isolated retina of FO
      fed rats as shown by higher levels of thiobarbituric acid reactive substances
      after incubation of retinal membranes with Fe2+/ascorbate. The retinal content of
      alpha-tocopherol was similar in SOY- and FO-fed animals. Light damage consisting
      of acute rod outer segment (ROS) disruptions was induced by exposing dark-adapted
      animals to 600 to 700 lux (230 to 260 microW/cm2) of white fluorescent light for
      30 minutes. Damage was quantitated using a computerized multifunctional image
      analysis of retinal thin sections. Although structural alterations of the ROS
      were present in both groups, FO-fed rats showed less damage at the base of the
      ROS. This occurred in spite of higher rhodopsin levels in FO-fed rats. There was
      no effect of diet on retinal morphology in dark-adapted rats. CONCLUSION: These
      results indicate that FO does not enhance the susceptibility to acute ROS disk
      disruptions in the rat retina. Our study further suggests that FO exerts a
      partial protective effect that may be related to changes in the formation of
      lipid mediators derived from EPA and AA in retinal phospholipids.

PMID- 8300367
TI  - Dietary deficiency of N-3 fatty acids alters rhodopsin content and function in
      the rat retina.
AB  - PURPOSE: To investigate the possibility that previously demonstrated reductions
      in photoreceptor sensitivity to light in n-3 fatty-acid-deficient rats can be
      explained by alterations in rhodopsin content and/or function. METHODS: Sprague
      Dawley rats were reared throughout gestation, lactation, and up to 24 weeks of
      age on a diet containing safflower oil (n-3 fatty-acid-deficient) or soybean oil
      as the sole source of lipids. Dark-adapted content and in vivo regeneration of
      rhodopsin after bleaching were measured by detergent extraction. The regeneration
      rate constants and number of photons absorbed by rhodopsin under steady-state
      bleach conditions were calculated from these values. The rate of metarhodopsin II
      (MII) formation in vitro was determined by flash bleaching extracted pigment and
      native rod outer segment membranes. Rod outer segment length and photoreceptor
      cell density were determined in histologic sections through the inferior central
      retina. RESULTS: Dark-adapted rhodopsin content of retinas from rats reared on
      safflower oil was 12% to 15% higher than that of rats raised on soybean oil at
      every age measured. The rate of rhodopsin regeneration was significantly slower
      in rats reared on safflower oil while the level of steady-state bleach was the
      same. This meant that the rats reared on safflower oil absorbed about one half as
      many photons during light exposure. The rate of metarhodopsin II formation in
      vitro was unaffected by n-3 fatty acid deficiency. No difference in either rod
      outer segment length or cell number was detected. CONCLUSION: A reduced capacity
      for photon absorption by rhodopsin could play a role in lowering retinal
      sensitivity to light in n-3 fatty-acid-deficient rats.

PMID- 8300369
TI  - Food allergies: how common are they?

PMID- 8300368
TI  - Legislature will address health system reform in 1994.

PMID- 8300370
TI  - Brave new world and CME.

PMID- 8300372
TI  - Future is good for women physicians.

PMID- 8300371
TI  - After the flood: the dripping faucet syndrome.

PMID- 8300373
TI  - Management of community-acquired pneumonia.
AB  - Pneumonia is one of the most common infectious illnesses treated by primary
      physicians. Accurate diagnosis requires a thorough history and physical
      examination, supplemented by a chest x-ray to confirm the presence of pneumonia
      and an adequate sputum sample to establish the etiologic agent. Empiric treatment
      is guided by a knowledge of the most likely organisms and their sensitivities in
      a particular community.

PMID- 8300374
TI  - Review of day case surgery.

PMID- 8300375
TI  - Kawasaki disease--the Northern Ireland experience.
AB  - In the period 1985-1991 inclusive, forty five cases of Kawasaki Disease were
      identified in Northern Ireland. The number of cases increased each year until
      1988 when the incidence was 19 per million population under 16 years, the highest
      reported for any region in the United Kingdom (data from British Paediatric
      Surveillance Unit). A high incidence of cardiac involvement was found, with
      18(40%) having proximal coronary artery dilatation or aneurysm. and 8(17.7%) with
      pericardial effusion detected by 2D Echocardiography during or shortly after the
      acute illness. One year after disease onset, persistent coronary artery changes
      were detectable by 2D Echocardiography in 53% of those initially affected. There
      have been no deaths and no patient has so far developed myocardial infarction.
      One patient has required coronary artery bypass grafting. A protocol for the
      acute management and long term follow-up of Kawasaki Disease is suggested.

PMID- 8300376
TI  - The role of computed tomography and sonography in acute bullous pemphigoid.
AB  - We report acute bullous pemphigoid occurring in an elderly female patient in whom
      abdominal sonography and computed tomography (CT) examinations revealed the
      presence of occult hepatic and splenic metastatic deposits from a primary
      pancreatic carcinoma. In the majority of cases bullous pemphigoid is a self
      limiting auto-immune disorder occurring in the absence of systemic disease. An
      association with visceral malignancy has been described by previous authors but
      the role of computed tomography and sonography in diagnosing occult malignancy
      and the subgroup of patients with pemphigoid in whom this should be undertaken
      has not been highlighted.

PMID- 8300377
TI  - Cardiopulmonary resuscitation skills in non consultant hospital doctors--the
      Irish experience.
AB  - We assessed the Cardiopulmonary Resuscitation (CPR) skills in 30 Non Consultant
      Hospital Doctors (N.C.H.D.'s) chosen randomly from a total of 110 on the staff of
      a university associated teaching hospital. The candidates filled out a
      questionnaire and were asked to perform initial assessment and CPR on a mannikin
      for two minutes. None of the candidates followed the recognised airway, breathing
      and circulation ABC sequence and only one provided effective CPR. We suggest
      there is a need for encouragement for doctors to undergo CPR training with
      subsequent certification and ongoing refresher courses during their career.

PMID- 8300378
TI  - Interferon-gamma and tumour necrosis factor production in patients with
      Helicobacter pylori infection.
AB  - The production of the cytokines, interferon-gamma and tumour necrosis factor by
      human antral mucosa cells and stimulated peripheral blood mononuclear cells were
      determined by enzyme linked immunosorbent assay and L929 bioassay respectively.
      Tumour necrosis factor production by peripheral blood mononuclear cells in
      response to Helicobacter pylori stimulation was depressed in Helicobacter pylori
      positive individuals, compared to Helicobacter pylori negative individuals (P <
      0.05). There was no difference in tumour necrosis factor production by peripheral
      blood mononuclear cells in response to purified protein derivative. However,
      tumour necrosis factor production by cells isolated from gastric mucosa during
      short term culture was significantly higher in Helicobacter pylori positive
      patients (P < 0.05) than negative patients, indicating a probable macrophage
      response. Levels of interferon-gamma did not differ significantly in the gastric
      explant culture from the two groups. The results show that Helicobacter pylori
      negative patients have a stronger peripheral cellular immune response to
      Helicobacter pylori infection. The higher levels of tumour necrosis factor
      production by antral mucosa cells in Helicobacter pylori positive patients may
      reflect the infiltration of T lymphocytes and macrophages within the local
      mucosa.

PMID- 8300379
TI  - Decompression sickness in Ireland--a review.
AB  - In the last decade there has been an increase in the incidence of decompression
      sickness in Ireland. The modern diver, equipped with specially developed diving
      equipment, is exposed to abnormal physiological conditions. This has resulted in
      a spectrum of medical conditions, which need to be recognised, diagnosed and
      treated. The department of Underwater Medicine at University College Hospital,
      Galway, is the only referral centre in the Republic of Ireland for patients
      suffering from decompression sickness. Early recognition and referral for
      treatment dramatically improves patient outcome. A one year's review of patients
      referred for treatment is presented.

PMID- 8300380
TI  - Percutaneous tracheostomy--an intensive care procedure.
AB  - Percutaneous tracheostomy (PCT) facilitates easy, bedside insertion of a
      tracheostomy tube. The percutaneous approach to tracheostomy is used in some
      parts of the world. This is the first report of a PCT method, in Ireland. The
      percutaneous technique appears to have advantages over conventional, surgical
      tracheostomy.

PMID- 8300381
TI  - Study of 45 pregnant opiate addicts in Dublin.

PMID- 8300382
TI  - Laron syndrome due to a post-receptor defect: response to IGF-I treatment.
AB  - Three siblings with Laron syndrome (LS) and normal serum growth hormone binding
      protein (GHBP) are described. Basal serum levels of hGH were high and IGF-1 low,
      and in contradistinction to the classical form of the disease serum GHBP and
      IGFBP-3 were normal in these patients. After 7 days of human growth hormone
      administration serum IGFBP-3 levels as well as the number of red blood cell IGF
      receptor sites increased. After short- and long-term IGF-1 administration the IGF
      1 receptor binding capacity as well as the number of IGF receptor sites decreased
      to levels found in control subjects. One year treatment with IGF-1 increased the
      growth velocity by 47-96% in the two older children. It is concluded that the
      findings described are compatible with a normal GH receptor and normal signal
      transmission for IGFBP-3 synthesis but a defect exists in the post-GH receptor
      mechanism for the generation of IGF-1. This is the first description of this type
      of defect leading to a variant of Laron syndrome.

PMID- 8300384
TI  - "King sized" hearts in infants: comparison of cardiac to body mass in ventricular
      septal defect in various age-groups.
AB  - Heart and body weight were reviewed in reports of 223 human cadavers. Of these,
      146 were of control (normal) hearts and 77 of hearts with ventricular septal
      defects. In each case the heart weight as a percentage of body weight was
      calculated (defined as pathological heart-body ratio). It was observed that under
      the age of 4 years, monstrous cardiomegalies may reach 3.2% of the total body
      weight. These "king sized" hearts were not found above the age of 4.

PMID- 8300383
TI  - Inferior wall myocardial infarction preceded by acute exudative pharyngitis in
      young males.
AB  - We conducted a comparative study in an intensive coronary care unit to elucidate
      the role of acute exudative pharyngitis in the setting of acute myocardial
      infarction (AMI). The subjects were 42 young male patients with AMI that was
      preceded by pharyngitis in 7 of them. Results showed that the site of the
      infarction was inferior in all those with preceding pharyngitis while only 33% of
      the other group had an inferior infarction. In patients with preceding exudative
      pharyngitis the coronary event was the first and only confrontation with the
      disease. Their prognosis was good, with normal exercise tests and absent coronary
      risk factors except for smoking in two patients and family history in one.
      Patients without pharyngitis had multiple coronary risk factors, with positive
      exercise stress tests in 46% and recurrent infarctions in 26%. Coronary
      arteriography was performed in four patients with pharyngitis and was normal,
      while multi-vessel disease was the rule in those without pharyngitis. We conclude
      that exudative pharyngitis may be followed by acute inferior myocardial
      infarction in young males and the diagnosis of infarction should be ruled out
      when such patients present with chest pains.

PMID- 8300385
TI  - Is the association between birthweight and height attainment independent of the
      confounding effect of ethnic and socioeconomic factors?
AB  - The association between birthweight and body height attainment at 17 years of age
      was investigated by studying a sample of 30,083 subjects born in Jerusalem
      between 1964 and 1971. Birthweights obtained from the computerized records of the
      Jerusalem Perinatal Study were matched with demographic and medical examination
      results available from the military draft boards. Linear regression models for
      standing height by birthweight were fitted for the data in order to adjust for
      the possible confounding effect of ethnic origin, socioeconomic status (as
      determined by parental education level), birth order and maternal age. Separate
      models were constructed for each sex. A significant (P < 0.0001) linear increase
      in standing height by birthweight of 3.33 cm/1,000 g was observed for the males
      (mean +/- SE height 174.5 +/- 0.1 cm) and 2.85 cm/1,000 g for the females (mean
      +/- SE height 163.5 +/- 0.1 cm). This positive linear association between body
      height at 17 years of age and birthweight was also demonstrated after
      stratification according to various categories of social class and ethnic origin.
      Adult body height was thus found to be strongly related to birthweight in both
      sexes, regardless of ethnic and socioeconomic influences.

PMID- 8300386
TI  - The clinical significance of Escherichia coli Alkalescens-Dispar in Tasmania.
AB  - An investigation in 1989 of human fecal specimens revealed that of 111 diarrheal
      samples examined Escherichia coli Alkalescens-Dispar (A-D) were found in 9
      (8.1%), but none were isolated from normal stool samples. Further studies have
      shown that although these isolates may be potential pathogens, they seem to
      remain unrecognized by routine laboratories due to their biochemical similarity
      to shigellae, a problem further exacerbated by their extensive sharing of O
      antigens. All the isolates were screened with an invasive DNA probe and all but
      three isolates were found to have a common plasmid. They were also confirmed to
      be invasive in HEp-2 monolayers. No isolates were shown to produce heat-labile or
      heat-stable toxin but electronmicroscopy revealed the presence of pili. The A-D
      isolates were biotyped using the two-tier schema of Crichton and Old and were
      categorized into biotypes 11, 12 and 16. These data confirm the importance of
      introducing an awareness of this intermediate strain into routine laboratories.

PMID- 8300387
TI  - Water quality, waterborne disease and enteric disease in Israel, 1976-92.
AB  - Israel experienced a large number of waterborne disease outbreaks between 1975
      and 1985, followed by a steep decline in the period 1986-92. Large-scale
      community waterborne disease outbreaks occurred primarily in the late 1970s, and
      in 1985 (the Krayot, four small towns neighboring Haifa), but substantial
      outbreaks occurred as late as 1989, with 4 during 1986-90, and 1 during 1991-92.
      New water standards, including mandatory chlorination of all community water
      supplies, came into effect in late 1988. Water quality, as monitored by the
      Ministry of Health, showed a marked improvement even when measured by the more
      stringent standards of the 1988 regulations. Long-term trends in the total of
      reported enteric infectious diseases from all sources, including typhoid,
      hepatitis, Shigella and Salmonella in Israel are examined. Typhoid, which has
      been declining since the 1960s, peaked in 1985 with the large waterborne disease
      episode of the Krayot. Shigella and total hepatitis incidence increased slowly up
      to the mid-1970s, followed by large increases during the 1975-85 period, then by
      a rapid decline up to 1991. Shigella, from childhood contacts in kindergartens,
      increased in 1992. Salmonella incidence continues to increase steadily. Mandatory
      chlorination and more stringent water standards have had an important impact on
      water quality and on waterborne disease outbreaks in Israel. Empiric evidence
      suggests that improving water quality may also be a factor in the changing
      patterns of some enteric diseases and the total burden of enteric disease in
      Israel.

PMID- 8300388
TI  - Effects of supra-therapeutic doses of isoniazid on liver function in the perfused
      rat liver.

PMID- 8300389
TI  - Amyloidosis of the pericardium in multiple myeloma: an unusual cause of bloody
      pericardial effusion.

PMID- 8300390
TI  - Relationships between HDL-C subfractions and HbA1C levels in non-insulin
      dependent diabetics.

PMID- 8300391
TI  - Genetic dwarfism with high growth hormone levels--multiple causation of GH
      nonresponsiveness.

PMID- 8300392
TI  - New insight into regulation of the extracellular fluid volume by aldosterone.

PMID- 8300394
TI  - Water--how much is too much?

PMID- 8300393
TI  - Laser-tissue interactions: vascular reactivity.

PMID- 8300395
TI  - Chloroquine overdose and leucopenia in Nigerians.

PMID- 8300396
TI  - The Ethiopian immigrations to Israel--medical, epidemiological and health
      aspects.

PMID- 8300397
TI  - Birthweight and ethnicity.

PMID- 8300398
TI  - The ethical will of Amatus Lusitanus.

PMID- 8300399
TI  - Otto Heinrich Warburg--pioneer in enzymatic biochemistry and physiology of
      respiration (1883-1970).

PMID- 8300400
TI  - Special article to the graduating class of 1993, John A Burns School of Medicine.

PMID- 8300401
TI  - The incidence of meconium-aspiration in Hawaii.
AB  - Meconium in the amniotic fluid was found in 2,633 obstetrical patients and
      meconium-aspiration occurred in 77 cases out of 14,527 deliveries. Although the
      incidence of meconium  in the amniotic fluid increased significantly at 39 weeks,
      a corresponding significant increase in meconium-aspiration did not occur until
      41 weeks gestation. All deaths associated with meconium, as well as 84% of the
      cases of severe meconium-aspiration syndrome, occurred in infants born of
      patients with oligohydramnios and a gestational age of 41 weeks or greater.

PMID- 8300402
TI  - A review of the anomalous origin of the left coronary artery from the anterior
      sinus of Valsalva: is prevention possible?
AB  - The origin of the left coronary artery from the anterior sinus of Valsalva is a
      rare coronary anomaly. Nevertheless, it remains an important pathological entity
      because of the possibility of its clinical and surgical consequences. Physicians
      should therefore be aware of this condition and consider it in their differential
      diagnosis of ischemic heart disease. This is a case report and review of the
      literature.

PMID- 8300403
TI  - Sugarcane workers: morbidity and mortality.
AB  - Sugarcane is, after pineapple, the largest agricultural industry in Hawaii. There
      have been reports that this industry poses certain health hazards. To investigate
      this possible hazard in Hawaii, the relationship of employment on a sugarcane
      plantation to total mortality, the development of definite coronary heart disease
      (CHD), stroke, cancer, lung cancer and certain risk factors were examined in men
      of Japanese ancestry participating in the Honolulu Heart Program. After 18 years
      of follow-up, those men who indicated one or more years working on sugarcane
      plantations had no significant difference in age-adjusted mortality, nor
      incidence of CHD, stroke, cancer, or lung cancer. There were no differences in
      risk factors compared to participants who were never employed on sugarcane
      plantations, nor were there differences in lung function as measured by FEV1.
      These findings were unchanged after adjusting for several potential confounding
      variables. No cases of mesothelioma were observed among those with a history of
      defined exposure. These findings were not due to a "healthy worker bias" and
      indicate that employment on a sugarcane plantation in Hawaii is not associated
      with elevated rates of chronic diseases.

PMID- 8300404
TI  - Endarterectomy and shunt: alternatives or in tandem?
AB  - There is no doubt about the efficacy of endarterectomy in the instance of
      localized occlusions of the arterial tree. The procedure was first developed in
      1946 and has been widely used. However, in the case of extensive, non-localized
      atheromatus disease of the aorta-iliac and the femoral-popliteal-tibial segments
      in the leg, the majority of vascular surgeons prefer the application of shunts or
      prosthetics. Nevertheless, there are proponents of extensive obliteration of the
      endothelium in these regions. There is also the possibility of combining both
      techniques. In order to assess the outcomes of the latter technique, we reviewed
      567 patients who were operated on for aorta-iliac and for femero-popliteo-tibial
      disease at Chelyabinsk Centre for Vascular Surgery in Russia from 1987 to 1991.
      Five hundred forty-one of these suffered from atherosclerosis. The other 26
      patients had non-specific inflammation of arterial system. The age distribution
      was 32 to 78 years; there were 551 men and 16 women. Ischemia in the degree of
      III to IV (according to the scale established by Fontain) was present in 341
      patients. Multi-site occlusions and associated multi-organ disease affected 213
      patients. Atheromatous disease was determined by ultrasonography, load tests and
      angiography.

PMID- 8300406
TI  - Differences in HLA class II alleles of isolated South American Indian populations
      from Brazil and Argentina.
AB  - We have studied the HLA class II alleles in 277 South American Indians, which
      included Argentinian tribes from the Gran Chaco: Toba (n = 135), Toba-Pilaga (n =
      19), Mataco-Wichi (n = 49), and Xavantes, a tribe from Central Brazil (n = 74).
      In the Brazilian tribe, only four DR groups were found: DRB1*1602 (gf = 0.303),
      DRB1*04 including DRB1*0404 (gf = 0.070) and DRB1*0407 (gf = 0.077), DRB1*0802
      (gf = 0.265), and DRB1*1402 (gf = 0.303). The HLA class II allele frequencies
      were similar among the different Argentinian tribes, and 90% of DRB1 alleles
      belonged to three families: DRB1*04 (including DRB1*0403, DRB1*0404, DRB1*0407,
      DRB1*0411, and DRB1*0417), DRB1*0802, and DRB1*14 (including DRB1*1402 and
      DRB1*1406). At the DPB1 locus, we found only seven alleles, the most frequent
      being DPB1*0402. Comparison of HLA class II alleles with those of North American
      Indians that we have previously studied shows that the frequency of some HLA
      class II alleles in Brazilian Xavantes resembles that of North American Indians
      more than that of the Argentinian Indian tribes. The allele DRB1*0417 was found
      exclusively in this population.

PMID- 8300405
TI  - Localization of immunoreactive tissue kallikrein in the seromucous glands of the
      human and guinea-pig respiratory tree.
AB  - An immunocytochemical study focused on the cellular localization of tissue
      kallikrein along the human and guinea-pig respiratory tracts is reported. A
      strong immunoreactivity for tissue kallikrein was observed in the seromucous
      glands of the nasal mucosa, trachea, and bronchi. In these glands, the
      immunostaining was restricted to the serous component of the acinus whereas
      mucous cells showed no staining. Since no immunoreactivity to kininogen was
      observed in any of the tissue constituents of the human and guinea-pig
      respiratory tree, transudation of the substrate from plasma was considered to be
      the preferred mode of delivery of the kininogen into the bronchopulmonary
      interstitium and lumen. Our results provide morphological evidence for the well
      documented presence of tissue kallikrein in bronchial lavage fluids and support
      the hypothesis that kinins may be one of the more important mediators involved
      during acute episodes of asthma and rhinitis.

PMID- 8300407
TI  - Multiple minor histocompatibility antigen disparities between a recipient and
      four HLA-identical potential sibling donors for bone marrow transplantation.
AB  - A patient with acute leukemia and her family including four HLA-identical
      siblings were analyzed to select a donor who was not only HLA- but also minor
      histocompatibility (mH) antigen compatible for allogeneic bone marrow
      transplantation (BMT). The HLA-A2 restricted mH antigen-specific HA-1, -2, -4,
      and -5 cytotoxic T-lymphocyte (CTL) clones were used to type the family members
      for expression of these mH antigens. The patient and one HLA-identical sibling
      were compatible for these mH antigens. This sibling was selected as the bone
      marrow donor. The patient engrafted promptly but developed acute and chronic
      graft-versus-host disease. To study the presence of other mH antigen disparities
      between recipient and donor, host-versus-graft CTL lines and clones were
      generated by stimulation of recipient peripheral blood lymphocytes (PBLs) with
      donor bone marrow cells, and graft-versus-host CTL lines were generated after BMT
      by stimulation of PBLs of donor origin with recipient bone marrow cells. These
      CTL lines were cytotoxic to cells from the bone marrow donor and from the
      recipient, respectively, and to cells from several other family members. T-cell
      lines, generated from the patient after BMT by stimulation of recipient-derived
      PBLs with donor bone marrow cells, exhibited no specific cytotoxicity to donor or
      recipient cells. Chimerism studies after BMT revealed that the PBLs and T-cell
      lines generated after BMT were of donor origin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300408
TI  - DR6 in Koreans. DR11 frequently acts as a recipient gene to create DR13 alleles.
AB  - DR6 is a complex allele family composed of at least 16 different alleles.
      Although 25% of Koreans express DR6 alleles, this allele family has not been well
      studied in the population. DNA samples obtained from 252 unrelated individuals
      were screened by PCR using Taq DNA polymerase and a DRB1 group-specific PCR
      primer set that amplifies the polymorphic second exon of DR3, DR11, and DR6 DRB1
      alleles. To identify the DR6 allelic frequencies in this population, PCR-positive
      samples were further analyzed by dot-blot hybridization using digoxigenin-labeled
      SSOPs. In this process, a new DRB1 allele was identified by its unique
      hybridization pattern and was further characterized by direct sequencing after
      PCR. The new DRB1 sequence is similar to DRB1*1101, differing at codon 47
      (TAC[Tyr]/TTC[Phe]) and at codon 58 (GCC[Ala]/GAG[Glu]). Based on sequence
      comparisons as well as its DRB3 and DQ associations, the new allele may have
      arisen by a gene conversion event from DRB1*1101. The resultant DR molecule bears
      DR6 serologic determinants as determined by serologic typing and, based on
      sequence, is probably a DR13 and not a DR14 allele. These data suggest that the
      DR11 allele has frequently acted as a recipient gene in the gene conversion
      events that created the subfamily of DR13 alleles, DRB1*1303, *1304, *1305, and
      the new allele described here.

PMID- 8300409
TI  - T-cell receptor V-gene usage in synovial fluid lymphocytes of patients with
      chronic arthritis.
AB  - In this study we analyzed the usage frequencies of the TCR V-gene segments by
      alpha beta+ T cells present in synovial fluid of 17 patients with chronic
      arthritis, including rheumatoid arthritis. The results of this study, obtained
      from semiquantitative PCR analyses, showed that in all patients most of the TCR V
      alpha- and V beta-gene segments could be detected both in fresh PBMCs and in
      fresh SFMCs. The relative frequencies of use of these V-region genes were
      variable between the different patients. Although there was some skewing of
      increased usage frequencies of particular TCR V alpha and V beta genes among SFMC
      derived TCRs when compared with PBMCs, we could not correlate such increased TCR
      V-gene usage with the inflammation in the joints as a disease-specific marker.

PMID- 8300410
TI  - Recognition by HLA-A2-restricted cytotoxic T lymphocytes of endogenously
      generated and exogenously provided synthetic peptide analogues of the influenza A
      virus matrix protein.
AB  - Experiments were carried out to determine whether complexes between MHC class I
      molecules and synthetic peptides are representative of those formed under more
      physiologically relevant conditions, with peptides derived intracellularly from
      processed antigens. Lysis of cells sensitized with exogenously provided and
      endogenously generated peptide analogues of the optimal nonameric peptide 58-66
      (GILGFVFTL; derived from the influenza virus matrix protein) was compared.
      Endogenous loading was accomplished by expressing minigene DNA coding for alanine
      substituted analogues of peptide 58-66 in HLA-A2-positive cells. Susceptibility
      to lysis by HLA-A2-restricted, peptide-specific cytotoxic lymphocytes was
      compared with lysis of cells sensitized with the same synthetic peptides.
      Although results were quite comparable, differences were observed. The
      endogenously presented analogues 58-66L60A, G61A, T65A, and L66A were recognized
      more efficiently than the corresponding exogenously presented analogues. This
      difference in recognition was most striking for peptide 58-66G61A. These results
      indicate the need for caution in using synthetic peptides in defining peptide
      binding motifs. Additional experiments with endogenously expressed analogues of
      58-66 with substitutions other than alanine were carried out to define the
      interaction between this peptide and HLA-A2. Results are compatible with the
      interpretation that residues 58, 59, and 60 interact with pockets A, B, and D,
      respectively, in the HLA-A2 binding groove and that these interactions contribute
      to peptide binding.

PMID- 8300411
TI  - A new microcellular cytotoxicity test based on calcein AM release.
AB  - We present a microtest for cell-mediated immunity, based on the use of the
      Tarasaki tray and calcein AM vital dye. The number of target cells needed has
      been reduced to 500 per test with a corresponding tenfold reduction in the number
      of effector cells needed. Results were read at the rate of 1 second per test
      using a fluorimeter attached to a microscope. Each reaction was also confirmed
      visually with the use of ethidium bromide as a counterstain for dead cells. The
      calcein AM dye used to stain the living cells was shown to have a low spontaneous
      leakage rate--less than 15% in 4 hours at 37 degrees C. Dilutions of targets
      stained by calcein AM had a linear relationship with measured fluorescence
      values. NK cells, LAKs, and CTLs were readily detectable by this microtest.
      Quantitation of killing and kinetic analysis was readily performed with this test
      system. A significant positive correlation to 51Cr-release results was found. We
      conclude that the microtest should find wide application in studies of cell
      mediated immunity.

PMID- 8300413
TI  - Morphological aspects of chromaffin tissue: the differential fixation of
      adrenaline and noradrenaline.
AB  - The morphological aspects of chromaffin tissue are reviewed, based mainly on our
      studies on the mouse adrenal gland. Particular attention was focused on the
      differential fixation of adrenaline and noradrenaline, and on the uptake and
      storage of [3H]dopa, [3H]dopamine and related substances in the adrenaline
      storing (A) and noradrenaline-storing (NA) cells. Scanning electron microscopy
      combined with the NaOH-maceration method was useful for demonstrating the 3
      dimensional organisation of nerve terminals, chromaffin cells, glial elements and
      vascular elements. In transmission electron microscopy, 3 types of chromaffin
      cell were distinguished. They were A, NA and SGC (small granule chromaffin)
      cells. After glutaraldehyde fixation followed by postosmication, A cell granules
      showed lower electron density, whereas NA cell granules were solid and dark. This
      difference in appearance between A and NA cells was first explained by the
      hypothesis that, after glutaraldehyde fixation, most of the adrenaline dissolved,
      whereas noradrenaline was precipitated in situ. Later, this hypothesis was
      supported by a series of autoradiographic and radioisotopic assay studies using
      [3H]dopa, [3H]dopamine and related substances; when [3H]adrenaline occurred,
      radioactivity in A cells mostly disappeared in the specimen, whereas that in the
      NA cells remained. At 15-60 min after an i.p. injection of [3H]dopa or
      [3H]dopamine, the concentration of radioactivity in A cells was higher than that
      in NA cells. However, in hypophysectomised mice, the radioactivity was low and
      evenly distributed in these 2 types of chromaffin cell. It was deduced that the
      carrier activities for extracellular dopa and dopamine were made greater in the A
      cells than in the NA cells by the pituitary gland. The hypophysectomy effects
      were restored by i.p. administration of ACTH.

PMID- 8300412
TI  - The chromaffin cell: paradigm in cell, developmental and growth factor biology.
AB  - This article reviews the chromaffin cell in relation to studies that have
      elucidated fundamental phenomena in cell biology (the molecular anatomy of
      exocytosis) and developmental neuroscience (the principle of neuropoiesis in the
      development of the sympathoadrenal cell lineage). A final section addresses
      growth factor synthesis and storage in chromaffin cells and their implications
      for the treatment of neurological disorders, such as Parkinson's disease.

PMID- 8300416
TI  - The innervation of the mammalian adrenal gland.
AB  - Early conflicting reports and the lack of sensitive anatomical methods have led
      to an oversimplified view of adrenal gland innervation. It was not until the
      introduction of nerve fibre tracing techniques in the mid-1970s that the true
      complexity of adrenal innervation began to emerge. The first part of this article
      comprises a brief review of these and other relevant reports dealing with both
      medullary and cortical innervation. In the second part a detailed account is
      given of the work undertaken in Rex Coupland's Department relating to the
      innervation of the rodent and primate adrenal medulla using a retrograde
      fluorescent tracer technique. It was concluded that, in all 3 species studied,
      the adrenal medulla receives a sympathetic and parasympathetic efferent and an
      afferent innervation. The possible interrelationship between neural control of
      cortical and medullar secretions is discussed briefly.

PMID- 8300415
TI  - Novel peptides from adrenomedullary chromaffin vesicles.
AB  - The adrenal medulla chromaffin vesicle (CV) contains, on a weight basis, as much
      soluble protein and peptide as catecholamine. The bulk of the protein is
      accounted for by chromogranins (Cgr) A, B and C. Additionally, a large variety of
      neuropeptides and their precursor proteins have been found recently within these
      vesicles. Nevertheless, fractionation of CV lysates indicates the presence of
      many more peptides than previously reported. In the hope of finding novel
      bioactive peptides, we initiated a systematic isolation and characterisation of
      CV peptides. Bovine CV pellets were prepared by sucrose gradient centrifugation
      and immediately boiled in water to avoid degradation of native proteins and
      peptides. The water lysates were fractionated through a battery of reversed-phase
      and ion-exchange high-performance chromatographic steps. We fully or partially
      characterised a substantial number of novel peptides derived from CgrA and CgrB.
      A tetradecapeptide and a 13 kDa extended peptide were derived from the bovine
      homologue of rat secretogranin III. Peptides corresponding to C-terminal
      fragments of 7B2 and proteoglycan II were also found. Additionally, several
      sequences had no known precursors. Of the sequences derived from known precursors
      some corresponded to fragments bracketed by pairs of basic amino acids, but
      others were preceded or followed by single basic residues or by unusual putative
      cleavage sites. Some of these peptides were postranslationally modified
      (pyroglutamylation, glycosylation, phosphorylation, amidation). A significant
      degree of structural conservation of some of these peptides across species
      suggests that they may exert biological effects when cosecreted with
      catecholamines during splanchnic stimulation.

PMID- 8300414
TI  - The adrenal chromaffin granule: a model for large dense core vesicles of
      endocrine and nervous tissue.
AB  - More than 25 years have elapsed since R. E. Coupland made his classic
      observations on the ultrastructure of chromaffin granules, on the histochemical
      differentiation of noradrenaline and adrenaline storage granules and on their
      release by exocytosis. This essay attempts to demonstrate that subsequent studies
      on the biochemistry of chromaffin granules have yielded analytical and functional
      data relevant for all large dense core vesicles of endocrine and nervous tissue.

PMID- 8300418
TI  - Exocytosis in adrenal chromaffin cells.
AB  - Recent advances have led to an increased understanding of the Ca(2+)-signalling
      pathway leading to exocytosis in bovine adrenal chromaffin cells. Video-imaging
      studies have allowed the temporal and spatial aspects of the Ca2+ signal to be
      investigated in detail. Ca2+ entry at the plasma membrane appears to be crucial
      for the activation of exocytosis. Ca2+ can enter through the nicotinic channel or
      characterised voltage-activated channels, or through other poorly defined
      pathways due to a variety of agonists. Emptying of internal Ca2+ stores is
      sufficient to activate a Ca2+ entry pathway. The elevation of cytosolic Ca2+
      concentration leads to a reorganisation of the cortical actin network and to the
      triggering of exocytosis. Studies on permeabilised chromaffin cells have resulted
      in the identification of some of the proteins that control Ca(2+)-dependent
      exocytosis. These include the peripheral plasma membrane protein annexin II and
      the cytosolic proteins, protein kinase C and 14-3-3 proteins (Exo1).

PMID- 8300417
TI  - Autonomic control of adrenal function.
AB  - Recent studies of adrenal function in conscious calves are reviewed. These have
      involved collecting the whole of the adrenal effluent blood from the right
      adrenal gland at intervals and, where necessary, prior functional hypophysectomy
      by destruction of the pituitary stalk under general halothane anaesthesia 3 d
      previously. The adrenal medulla was found to release numerous neuropeptides, in
      addition to catecholamines, in response to stimulation of the peripheral end of
      the right splanchnic nerve, which was carried out below behavioural threshold.
      Many of these responses were enhanced by stimulating intermittently at a
      relatively high frequency. Intra-aortic infusions of a relatively low dose of
      acetylcholine (4.5 nmol min-1 kg-1) elicited similar responses. In the adrenal
      cortex, agonists which either potentiated the steroidogenic response to ACTH or
      exerted a direct steroidogenic action included VIP, CGRP, CRF and ACh acting via
      muscarinic receptors. Stimulation of the peripheral end of the right splanchnic
      nerve strongly potentiated the steroidogenic response to ACTH and there is
      compelling evidence that the innervation normally plays an important part in
      cortisol secretion.

PMID- 8300419
TI  - Kinetics of adrenal medullary cells.
AB  - The adrenal medulla of mammals has a heterogeneous population of cells. In adults
      most are epithelial cells containing a particular type of cytoplasmic granule.
      Based on a variety of cytochemical and ultrastructural studies it is now accepted
      that 2 different adrenal medullary chromaffin cell types can be distinguished,
      i.e. noradrenaline (NA) and adrenaline (A) synthesising and storing cells. Other
      cell types present in the adrenal medulla include neuronal elements comprising
      either cell bodies or nerve fibres entering from outside the gland (extrinsic
      innervation). It is assumed that adrenal medullary cells have a limited life
      span, i.e. they are replaced after a certain period. Data on this replacement
      process are scarce. Recently, we initiated an investigation into this question
      using cytochemical procedures that enable the detection of DNA duplication to
      measure mitotic activity in individual cells. Female Sprague-Dawley rats aged 22
      36 wk received a single i.p. injection of BrdU or BrdU was administered
      continuously via an implanted mini-osmotic pump. Cell nuclei that had
      incorporated BrdU were demonstrated using an indirect immunoperoxidase staining
      technique. At 1 h after a single injection, 0.46 +/- 0.07% of the adrenal
      medullary (chromaffin) cells were labelled. This increased to 0.77 +/- 0.08%
      after 12 h with no further increase during the next 7-8 d. With continuous
      infusion of BrdU the fraction of labelled cells increased gradually to about 40%
      after 73 d (the longest period studied). These results show that in adult rats
      adrenal medullary cells are able to divide, although at a slow rate (renewal rate
      of about 1%/day).

PMID- 8300421
TI  - Development of the eye in the North American opossum (Didelphis virginiana).
AB  - Marsupials are unique models for developmental biology-oriented research because
      of the immature state of their development at birth. The North American opossum
      (Didelphis virginiana) has several advantages over other marsupials, including
      large litter size, short prenatal period (12.5 d), an extended postnatal period
      while accessible in the pouch, and its ability to reproduce reliably in
      captivity. Studies of ocular development in this species have not been reported
      previously. The aim of the present investigation was therefore to document the
      major landmarks in prenatal and postnatal development of the cornea, lens, iris,
      ciliary body and retina. Fifteen embryos (10.5, 10.7 and 11 d postconception and
      6 h after birth [12 d]) were studied by paraffin histology. Eyes of pouch young
      at 8 d, 2, 6, 9 and 13 wk were studied by transmission electron microscopy and
      light microscopy. The study revealed a similar pattern of ocular development in
      Didelphis to other metatherian and eutherian mammals. Differentiation of the eye
      is particularly rapid in the 2 d before birth. For example, although the lens
      vesicle separates from the surface ectoderm on d 10, by birth (2.5 d later) a
      primitive cornea and fused eyelids have formed, presumably to protect the eye
      during migration to the pouch. At birth the retinal pigment epithelium (RPE)
      contains melanin; however, the inner layer of the optic cup does not
      differentiate into an inner and outer neuroblastic layer until 8 d after birth.
      Around 6 wk after birth most components of the adult eye are identifiable, albeit
      in an immature form. These include the corneal layers, the iris (including the
      sphincter pupillae), ciliary processes, RPE tapetum, and a fully laminated retina
      with immature photoreceptors. A knowledge of the timing of major events in eye
      development in Didelphis and their comparison with equivalent events in human eye
      development should allow the appropriate choice of stages for any future
      experimental studies utilising this marsupial species.

PMID- 8300422
TI  - Comparative anatomical studies on the thyroid and thymic arteries. II.
      Polyprotodont marsupials.
AB  - The thyroid and thymic arteries were investigated in 27 specimens from 9 species
      belonging to the Australian Polyprotodont marsupials, which are subdivided into 2
      superfamilies, Dasyuroidea and Perameloidea. The results were compared with those
      in rats and humans. The site of origin of the superior thyroid artery ranged from
      the external carotid artery to the common carotid in Dasyuroids, and converged on
      the external carotid and the bifurcation of the common carotid in Perameloids.
      The course of the superior thyroid artery suggested that it was originally the
      pharyngeal artery rather than an artery of the thyroid gland. Because the so
      called inferior thyroid artery in Polyprotodonts has fewer relationships with the
      gland than in rats and humans, it is preferable to refer to it as the tracheo
      oesophageal artery. The inferior thymic artery was constantly present in both
      groups. The middle thymic artery was rare, only appearing in 2 specimens of
      Dasyuroids. The supreme thymic, superior thymic (both abundant in rats and
      humans) and the middle thymothyroid (abundant in humans) arteries were absent.
      These results suggest that the arterial pattern of both organs in Perameloids is
      simpler than in Dasyuroids and that the pattern of the Polyprotodonts, as a
      whole, is simpler than in the rat or man.

PMID- 8300420
TI  - Comparative morphology, cytochemistry and innervation of chromaffin tissue in
      vertebrates.
AB  - Chromaffin cells were observed singly or in clusters in the heart and sympathetic
      cord of 2 genera of dipnoan fish, Protopterus and Lepidosiren. They were
      invariably found in close association with the autonomic sympathetic nervous
      system and at sites where chromaffin cells or their precursors are situated in
      mammals during ontogenetic development. X-ray microanalysis demonstrated that
      they contained a primary catecholamine which was identified
      microspectrofluorometrically as dopamine. The chromaffin cells were innervated by
      efferent axons with typical preganglionic sympathetic terminals which were
      acetylcholinesterase-positive. Although the general morphology and cytochemistry
      agree with those of developing intra-adrenal chromaffin cells in mammals, the
      morphological characteristics implicate them as active secretory gland cells. The
      dopamine transmitter phenotype seems to be determined by the maintenance
      throughout life of the separate and distant location of steroidogenic interrenal
      tissue from suprarenal elements.

PMID- 8300423
TI  - The embryological development of primary visual centres in the turtle Emys
      orbicularis.
AB  - The development of the primary visual centres was studied in a series of embryos
      of the turtle, Emys orbicularis, incubated at 25 degrees C. The differentiation
      of both visual and nonvisual diencephalic and mesencephalic structures takes
      place entirely within the 2nd quarter of the period of incubation; this finding
      appears to be consistent with previous descriptions of the embryology of 2 other
      chelonian species, Lepidochelys and Chelydra. Two successive waves of migration,
      each dividing into internal and external sheaves, are involved in the formation
      of the structures of the diencephalon and mesencephalon. The primary visual
      centres, which comprise 2 hypothalamic, 5 thalamic and 5 pretectal zones of
      retinal projections, together with the 2 superficial layers of the tectum and a
      single tegmental projection zone, all have their origin in the external sheaf of
      the 1st wave of migration. The finding that the adult nucleus geniculatus
      lateralis dorsalis, pars ventralis arises from one of the migrations of the
      dorsal thalamus is discussed in the context of the debate over the possible
      homologues of the mammalian geniculostriate visual pathway.

PMID- 8300424
TI  - Intraventricular macrophages in the lateral ventricles with special reference to
      epiplexus cells: a quantitative analysis and their uptake of fluorescent tracer
      injected intraperitoneally in rats of different ages.
AB  - The labelling of epiplexus cells associated with the choroid plexus in the
      lateral ventricles was examined in rats of different ages with the fluorescent
      dye, rhodamine isothiocyanate (RhIc). A quantitative study was also attempted;
      this showed that the number of epiplexus cells and their related cells, namely
      supraependymal and free-floating cells, increased with age. The mean absolute
      number of epiplexus cells ranged from approximately 700 in the newborn to
      approximately 2200 in rats of 17 d of age; thereafter it remained unchanged. The
      number of free-floating cells also increased substantially but showed
      considerable individual variation. Following i.p. injection, the tracer was
      rapidly taken up by the epiplexus cells. This provided strong support for their
      phagocytic nature. In the newborn (1 d) and developing (13 d, 17 d) rats, RhIc
      labelled epiplexus cells were first observed 3 h after the injection. In adult
      rats, labelled cells were not observed until 12 h after injection. In either
      case, the fluorescence in the epiplexus cells gradually increased with time. It
      is suggested from this study that the blood-CSF barrier in the choroid plexus in
      postnatal rats is incomplete, thereby allowing a rapid transvascular diffusion of
      the injected RhIc into the blood circulation. The fluorescent dye which enters
      the ventricle by way of the choroid epithelium is subsequently taken up by the
      epiplexus cells. Such an unimpeded passage, however, is reduced in the adult
      rats, probably due to the maturation of the blood capillaries as well as the
      choroid epithelium.

PMID- 8300425
TI  - Scanning electron microscopy of goat oviductal epithelial cells at the follicular
      and luteal phases of the oestrus cycle.
AB  - The luminal surfaces of epithelial cells in various regions of the oviducts of
      the goats at the follicular and luteal phases of the oestrous cycle were examined
      by scanning electron microscopy. Marked cyclic changes were observed on the
      surface of the epithelium in the fimbriae, ampulla and ampullar-isthmic junction,
      but few changes were found in the isthmus or uterotubal junction. The epithelium
      of the fimbriae, ampulla, and ampullar-isthmic junction of oviducts in the
      follicular phase was extensively ciliated and most of the cilia extended above
      the apical processes of the nonciliated cells. In the luteal phase, many ciliated
      cells were hidden by the bulbous processes of the nonciliated cells. In the
      isthmus and at the uterotubal junction, the apical surfaces of the nonciliated
      cells were flat or gently rounded at both phases of the oestrous cycle. The
      results demonstrate that regional variations are associated with the cyclic
      changes in the epithelial cells of the goat oviduct.

PMID- 8300426
TI  - The tammar wallaby (Macropus eugenii) and the Sprague-Dawley rat: comparative
      anatomy and physiology of inguinoscrotal testicular descent.
AB  - Inguinoscrotal testicular descent in the tammar wallaby (Macropus eugenii) and
      the Sprague-Dawley rat was studied by macroscopic dissection, histological
      evaluation and organ culture bioassay. In 3 or 4 d Sprague-Dawley rats (n = 10)
      the gubernacular tip bulged free from the surrounding tissues, particularly with
      the application of abdominal pressure. Microscopic examination revealed that only
      the body of the gubernaculum is connected posteriorly to the pubic region. In
      contrast, macroscopic dissection of male tammar wallabies (n = 17) revealed a
      densely adherent distal gubernacular attachment to the inside of the fibrous
      scrotal bulge while the body of the gubernaculum was less firmly attached. These
      attachments were present throughout the process of testicular descent,
      illustrating an important anatomical difference between these species. The
      gubernaculum from the tammar wallaby pouch young was studied in organ culture
      with rat calcitonin gene-related peptide for 4 d. Rhythmic gubernacular
      contractions similar to those documented previously in the rat were not observed.
      The hypothesis proposed in the rat for the control of inguinoscrotal gubernacular
      migration via the genitofemoral nerve and its neurotransmitters may not be
      applicable in marsupial mammals.

PMID- 8300428
TI  - Fine structure and development of ionocyte areas in the labyrinth of the trout
      (Salmo trutta fario).
AB  - The distribution of ionocyte areas in the trout labyrinth (in the semicircular
      canal ampullae, crus communis and utricular vesicle) is very similar to that of
      areas of dark cells in mammals. In all 3 regions, ionocytes begin to develop
      after hatching, and are cuboid at fry stages and prismatic in juveniles and
      adults. On electron microscopy, 3 types of cell can be seen in adult ionocyte
      areas: ionocytes, associate cells and basal cells. Ionocytes possess many
      mitochondria, occupying approximately 28% of the cytoplasmic volume, and a well
      developed tubulomembranous system which opens on the basal surface at some
      points. These ultrastructural features, very similar to those of chloride cells,
      strongly suggest that ionocytes are involved in ion transport. Unlike mammalian
      dark cells, there are no basal or lateral infoldings of the plasma membrane in
      trout ionocytes. Trout associate cells have a well developed vacuolar system, few
      mitochondria and bundles of cytoplasmic filaments. Although less specialised than
      ionocytes, they may be involved in endolymph secretion.

PMID- 8300427
TI  - Myopathy in vitamin E deficient rats: muscle fibre necrosis associated with
      disturbances of mitochondrial function.
AB  - Vitamin E deficiency in rats gives rise to a neuromuscular syndrome that includes
      a peripheral neuropathy as well as generalised muscle wasting and weakness. This
      is probably related to damage by oxygen-derived free radicals. In the present
      study, histological examination of lower limb muscles showed widespread myopathic
      changes which included the presence of amorphous electron-dense inclusions and
      tubular aggregates in muscle fibres and muscle fibre necrosis. Histochemical
      observations suggested a reduction in the activity of oxidative enzymes. The
      mitochondria showed nonspecific degenerative changes on electron microscopy; no
      paracrystalline inclusions were observed. Polarographic analysis of isolated
      muscle mitochondria revealed statistically significant decreases in oxygen
      utilisation rates with both NADH and FADH2-linked substrates. In confirmation of
      a generalised respiratory chain abnormality, enzymatic analyses revealed
      decreases in the activities of complexes I, II/III and IV, although only the
      decreases in complexes I and IV activities were statistically significant.
      Measurements of membrane fluidity showed that this is reduced in mitochondria
      from vitamin E deficient rats, indicating reduced stability of their membranes.
      The respiratory control ratio, derived from the polarographic results, was also
      reduced in mitochondria from vitamin E deficient animals, suggesting membrane
      damage. An altered lipid environment, possibly secondary to a higher level of
      lipid peroxidation, could result in the inhibition of complexes I and IV. This
      could also be caused by oxidative damage to the complexes or to mitochondrial
      DNA. The preservation of citrate synthase activity is against any generalised
      defect of mitochondrial function. The question as to whether these defects of
      mitochondrial respiratory chain function are responsible for the muscle fibre
      damage and necrosis requires further investigation.

PMID- 8300429
TI  - Spermiogenesis and spermiation in the Japanese quail (Coturnix coturnix
      japonica).
AB  - The ultrastructure of 12 steps of spermatid development and the process of
      spermiation are described for the Japanese quail in order to clarify the
      classification proposed for determining the stages of the cycle of the
      seminiferous epithelium (Lin et al. 1990) and to assess disagreements in the
      literature about sperm development in birds. It was concluded that acrosomal
      development involves the formation of proacrosomal granules which do not contain
      dense granules like the mammalian acrosome. Material which forms the
      perforatorium initially accumulates as a nuclear granule before appearing in the
      subacrosomal space. A circular and longitudinal manchette develop sequentially
      during nuclear elongation. Microtubules of the circular manchette initially form
      around several parts of the spherical nucleus of step 4 spermatids and
      subsequently occur most frequently around the narrowest regions of the elongating
      nucleus. Fibrous sheath development starts in step 2 spermatids indicating that
      it forms much earlier in the quail than in mammals. Spermiation differs from the
      process described in mammals in that the residual body is released from near the
      rostral end of the sperm nucleus leaving no cytoplasmic droplet in quail
      spermatozoa.

PMID- 8300430
TI  - Blood supply to the cranial venae cavae and the heart in the laboratory shrew
      (Suncus murinus).
AB  - The blood supply to the cranial venae cavae on both sides and to the heart was
      studied macroscopically in 40 adult laboratory shrews (Suncus murinus) of both
      sexes injected either with Neoprene latex into the abdominal aorta (25 animals)
      or with Mercox into the left ventricle (15 animals). The 1st branch of the left
      subclavian artery in 23 animals of the 1st group ramified caudal to the aortic
      arch and descended between the aorta and the trachea to supply mainly the large
      left cranial vena cava that lay on the dorsal surface of the left atrium, while a
      branch that arose between the 1st and 2nd intercostal arteries on the right in 25
      animals supplied the right cranial vena cava caudally after giving rise to a
      branch to the oesophagus. In 2 animals the artery to the left vena cava arose
      directly from the thoracic aorta at the level of the 4th intercostal artery and
      then followed the course described above. From these considerations, these
      vessels in the laboratory shrew would correspond to the accessory coronary
      arteries of Halpern (1957) in the rat. In the 15 animals of the 2nd group, the
      left coronary artery was distributed to the atrium and the ventricle on left side
      and to the upper half of the interventricular septum, the artery on the right
      supplied the atrium and the ventricle on right side, the interatrial septum and
      lower half of the interventricular septum.

PMID- 8300431
TI  - The effects of mode of delivery and sex of newborn on placental morphology in
      control and diabetic pregnancies.
AB  - Placentae from control and diabetic subjects were analysed using stereological
      techniques in order to assess the effects of mode of delivery (vaginal versus
      caesarean) and sex of neonate on parenchymal morphology. Effects were assessed
      using indices of peripheral villous and fetal capillary growth, villous maturity,
      extent of maternal intervillous space and thickness of intervascular tissue
      layers. Placentae were from pregnancies (37-42 wk) which were either
      uncomplicated (control group) or complicated by diabetes mellitus (diabetic
      group, White class D) which was reasonably well controlled in terms of glucose
      and glycated haemoglobin levels. Neonatal and placental weights were recorded and
      placentae sampled in a systematic random fashion. Fields of view on formalin
      fixed, paraffin-embedded sections were analysed to obtain estimates of volumes,
      surface areas, lengths and diffusion (harmonic mean) distances. Comparisons were
      drawn using 3-way analyses of variance with group, mode of delivery and sex as
      the principal effects. The mean length of gestation was 2 wk longer in controls
      (39 versus 37 wk). Despite this, mean birth weight was similar (3.5 kg) in
      control and diabetic groups. Moreover, diabetic placentae were 17% heavier and
      showed shorter fetal plasma distances (30%) and larger fetal capillaries (volume
      45%, surface 39% and length 30% greater). Mode of delivery had significant main
      and interaction effects on stromal diffusion distance (25% greater in vaginal
      deliveries) and an interaction effect on fetal capillary volume. Sex had
      significant main effects on the maternal plasma distance (21% greater in males)
      and capillary volume (30% bigger in males) and an interaction effect on placental
      weight and mean capillary diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300433
TI  - The biomechanical ambiguity of the articular surface.
AB  - A series of micromechanical tests carried out on the articular surface of
      cartilage have provided an accurate description of the mechanical properties of
      any one site with respect to the orientation framework obtained from its
      characteristic split-line direction. Ultrastructural studies revealed little
      evidence that the split-line direction correlated strongly with any preferred
      alignment of fibrils. This paper therefore offers a new interpretation of the
      biomechanical significance of the widely used split-line test for the articular
      surface of cartilage.

PMID- 8300432
TI  - Neuroepithelial bodies in the Fawn Hooded rat lung: morphological and
      neuroanatomical evidence for a sensory innervation.
AB  - The lungs of young Fawn Hooded (FH) rats contain neuroepithelial bodies (NEB)
      with a very dense innervation. They are covered by a unicellular layer of
      flattened Clara cells and their apices protrude slightly into the airway lumen.
      The NEB corpuscle cells are loaded with dense core vesicles and are potentially
      capable of secretion by basal exocytosis. Since they are exposed to the airspace
      by narrow pores between the covering Clara cells, they may be influenced by the
      composition of the inhaled air. Facilitated uptake of the secreted substances
      into the bloodstream is indicated by the presence of extensively fenestrated
      capillaries in the corium beneath the NEB. The NEB are richly innervated by nerve
      fibres which loop through the corpuscle and form 'en passant' nerve endings. Most
      of these are packed with mitochondria and are morphologically afferent nerve
      endings. A much rarer type of nerve ending contains cholinergic-type vesicles and
      is morphologically efferent. Since both types are often observed in cytoplasmic
      continuity, the secretory activity of the NEB may be locally modulated by axon
      reflexes. The nerve endings often display synaptic junctions with the NEB
      corpuscle cells, which are invariably oriented towards the central nervous
      system. The sensory nature of the NEB innervation was confirmed by the results of
      neuroanatomical experiments. Infranodose vagotomy led to degeneration and
      disappearance of ipsilateral NEB intracorpuscular nerve endings, while
      supranodose vagotomy had no significant effect. In contrast to these findings,
      the end bulbs of preganglionic nerve fibres synapsing with intrapulmonary
      ganglion cells degenerated and disappeared after both procedures of vagotomy.
      Therefore, the nerve endings observed in pulmonary NEB must be derived mainly
      from vagal nodose (i.e. sensory) ganglion cells. It is concluded that although
      their precise functional significance remains obscure, pulmonary NEB in the Fawn
      Hooded rat appear to be well adapted to act both as endocrine glands and receptor
      organs.

PMID- 8300434
TI  - Early embryonic angiogenesis in the chick area vasculosa.
AB  - The rate and pattern of growth as well as vessel ultrastructure of the area
      vasculosa were examined in the chick. The embryos were grown in shell-less
      culture after 3 d in ovo and staged according to Hamburger & Hamilton (1951) and
      the rate of increase in the diameter of the area vasculosa was measured. This
      revealed an increase in the area vasculosa diameter of 0.4 +/- 0.02 mm h-1 (n =
      62) for embryos between stages 15 and 20. To determine the growth pattern of the
      sinus terminalis (the advancing edge of the area vasculosa), a marked length of
      the sinus was photographed at hourly intervals over a period of 9 h. It was found
      that this vessel grows by new vessels forming external to the sinus in the form
      of parallel plexuses, one of which then replaces the original sinus as the major
      route of bloodflow. Ultrastructurally the capillaries of the area vasculosa were
      simple tubes of endothelial cells, lacking a basement membrane. The endothelial
      cell cytoplasm contained only a few organelles, mainly mitochondria and rough
      endoplasmic reticulum. These findings indicate that the chick area vasculosa
      capillaries bear similar structural and growth characteristics to those
      associated with tumour angiogenesis and suggest that they may prove to be a
      useful model system for studying the factors involved in pathological
      angiogenesis.

PMID- 8300435
TI  - The spiral fold of the caecum in the ostrich (Struthio camelus).
AB  - The caecum of the ostrich was observed to contain a fold that spiralled
      approximately 30 times, transforming the lumen into a long, spiral-shaped cavity.
      The fold consisted of mucosa, muscularis mucosa and submucosa. The proximal part
      of the fold also contained a central core of muscle originating from the inner
      circular muscle layer of the caecal wall. The distal part was expanded to form a
      'frill', thereby enlarging the surface area of the fold. Blood vessels entered
      the fold at the mesenteric border from where they were distributed to the fold
      and caecal wall. From its origin near the caecorectal junction, the fold rapidly
      increased in height to attain 2.75 +/- 0.95 cm at the 9th turn of the spiral.
      Thereafter it gradually decreased and disappeared approximately 14 cm from the
      apex of the caecum. The surface area of the spiral fold averaged 955.75 cm2 and
      constituted 54% of the total caecal mucosal surface. It is suggested that the
      fold plays an important role in the absorption of volatile fatty acids and other
      metabolites produced by microbial fermentation of cellulose and hemicellulose.

PMID- 8300436
TI  - Sexual dimorphism in the human face assessed by euclidean distance matrix
      analysis.
AB  - The form of any object can be viewed as a combination of size and shape. A
      recently proposed method (euclidean distance matrix analysis) can differentiate
      between size and shape differences. It has been applied to analyse the sexual
      dimorphism in facial form in a sample of 108 healthy young adults (57 men, 51
      women). The face was wider and longer in men than in women. A global shape
      difference was demonstrated, the male face being more rectangular and the female
      face more square. Gender variations involved especially the lower third of the
      face and, in particular, the position of the pogonion relative to the other
      structures.

PMID- 8300437
TI  - Effects of ACTH and aminoglutethimide on the catecholamine content and chromaffin
      cell morphology of the adrenal medulla of the neonatal rat.
AB  - The rat adrenal medulla is immature at birth, composed of phaeochromoblasts and
      undifferentiated chromaffin cells, but by 7 d postnatally morphologically
      distinct adrenaline-storing (A) and noradrenaline-storing (NA) cells can be
      distinguished in the adult proportions of approximately 80-85% A and 15-20% NA
      cells. Glucocorticoid hormones are known to play an important role in the initial
      expression and maintenance of phenylethanolamine N-methyl transferase (PNMT), the
      enzyme characteristic of A cells. The purpose of the study was to investigate the
      effects of glucocorticoids on the establishment of the A and NA cell phenotype in
      vivo during the first postnatal week. Neonatal rats were treated from postnatal d
      1 to 7 either with ACTH to increase circulating levels of glucocorticoids or with
      aminoglutethimide to reduce blood glucocorticoids. On postnatal d 7 the volume
      fractions of A and NA cells in the adrenal medulla were estimated and the amounts
      of stored adrenaline and noradrenaline determined by HPLC and compared with
      untreated controls. Adrenaline levels were increased following ACTH treatment and
      there was an apparent decrease after aminoglutethimide which was not
      statistically significant. There was cytological evidence of the effects of ACTH
      and aminoglutethimide on the adrenal cortex but no resultant effect on medullary
      cell morphology. A cells remained predominant with NA cells making up
      approximately 15% of chromaffin cells, suggesting that any effects of altered
      glucocorticoid levels were confined to a modulation of adrenaline synthesis by a
      morphologically unchanged chromaffin cell population.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8300438
TI  - Uptake of tracer by the epiplexus cells via the choroid plexus epithelium
      following an intravenous or intraperitoneal injection of horseradish peroxidase
      in rats.
AB  - Rapid passage of horseradish peroxidase (HRP) from the blood circulation to the
      cerebrospinal fluid was demonstrated in postnatal rats. At 30 min-1 h after an
      intravenous (i.v.) injection of HRP, the extravasated tracer from the blood
      vessels entered the connective tissue of the choroid plexus to reach the
      epithelial intercellular spaces where it was retarded by the apical tight
      junctions. The HRP which accumulated in widened intercellular spaces was readily
      endocytosed by the epithelial cells, notably at their lateral surfaces. This was
      especially pronounced 3 h after the injection. The endocytosed HRP was either
      routed to lysosomes or discharged apically by exocytosis into the CSF via
      membrane-bound vesicles by the epithelial cells. After longer survival periods,
      i.e. 6 h after injection, the intercellular spaces were relatively clear of
      tracer. HRP-labelled vacuoles or vesicles had diminished with a concomitant
      increase in the number of lysosomes containing HRP reaction product. In the
      course of HRP injection, the epiplexus cells residing on the choroid epithelium
      progressively accumulated HRP by endocytosis so that in rats killed 6 h after
      injection, the cells were heavily loaded with HRP incorporated into massive
      lysosomes. The labelling pattern of epithelial and epiplexus cells in rats
      injected intraperitoneally followed that observed in those receiving i.v.
      injections. These results suggest that the epiplexus cells together with
      lysosomal activity by the choroid epithelial cells serve as a protective line of
      defence for the blood-CSF barrier which appears to be inefficient.

PMID- 8300439
TI  - An investigation of the vascular organisation of the canine submandibular gland.
AB  - It is known that parasympathetic nerve stimulation elevates venous pressure in
      the dog submandibular gland, and that the venous pressure wave is transformed to
      that of the arterial pulse. The vascular arrangements and histological
      characteristics of the dog submandibular gland were therefore examined to
      establish which anatomical structures are responsible for the change in venous
      pressure during salivation induced by parasympathetic stimulation. The acinar and
      ductal circulations were found to be arranged in parallel and arteriovenous
      anastomoses were identified in both. Microsphere injection studies demonstrated
      the opening of arteriovenous anastomoses in actively secreting glands. Smooth
      muscle cells were rarely found in venous blood vessels but venous valves were
      abundant in both circulations. Dense connective tissue was observed to enclose
      the ductal system and its accompanying structures (blood vessels, lymphatic
      vessels and nerves); it was most abundant in the hilum and diminished aborally.
      The mechanism responsible for elevating venous pressure during parasympathetic
      salivation is thus probably related to opening of the arteriovenous anastomoses;
      the increase in the amount of surrounding dense connective tissue in a central
      direction may facilitate the preservation of the transmitted arterial pressure
      and pulse in the venous system.

PMID- 8300440
TI  - Arthritis of the subtalar joint associated with sustentaculum tali facet
      configuration.
AB  - The articular facets of the sustentaculum tali have a variety of configurations
      that are generally viewed as nonmetric traits of little functional significance.
      Bruckner (1987), in contrast, has hypothesised that sustentaculum tali facet
      variations are functionally important because they influence subtalar joint
      stability. To test this hypothesis, 191 calcanei were analysed for correlations
      between sustentaculum tali facet morphology and osteoarthritis of the subtalar
      joint. Calcanei with 2 separate sustentaculum tali facets had a lower frequency
      of arthritic changes associated with joint instability than calcanei with other
      facet configurations. This finding supports Bruckner's hypothesis that subtalar
      joint facet configuration is a factor in foot mobility.

PMID- 8300441
TI  - Deep and shallow forms of the sulcus for extensor carpi ulnaris.
AB  - Anatomical variations in the sulcus for the tendon of extensor carpi ulnaris were
      studied in 240 upper limbs. The sulcus lies between the head and the styloid
      process on the dorsal surface of the distal end of the ulna. This groove has deep
      and shallow forms and, rarely, a flat form. The sulcus was classified into 4
      grades according to its depth. Grade I, a deep sulcus, was found in 51.3%. Grades
      II and III are shallow, but the styloid process in grade II is more prominent
      than in grade III. The former was found in 28.8%, the latter in 14.2%. Grade IV
      is a flat form. This was rare and found only in 1.3%. This variation was not age
      related, but was a congenital feature.

PMID- 8300442
TI  - Phenotypic identification of the genus Enterococcus and differentiation of
      phylogenetically distinct enterococcal species and species groups.

PMID- 8300443
TI  - Examination of raw beef products for the presence of Vero cytotoxin producing
      Escherichia coli, particularly those of serogroup O157.
AB  - Fifty-four of 310 (17%) samples of raw beef products contained Vero cytotoxin
      (VT)-producing Escherichia coli (VTEC) detected by DNA probes for the VT genes.
      VTEC strains examined in detail from a selection of the positive samples belonged
      to several O serogroups, some of which have been associated with human diarrhoea
      or haemolytic uraemic syndrome. Some of the strains possessed properties that may
      contribute to virulence in man. None of the food samples contained VT-producing
      E. coli O157 when tested by a combination of VT probe tests and colony
      immunoblotting with commercially available anti-O157 serum. Quantification of the
      immunoblotting technique indicated that O157 VTEC could be recovered from
      artificially-inoculated meat samples at a level of less than one organism per
      gram. Five of the food samples carried E. coli O157 strains that did not produce
      VT and differed in other properties from O157 VTEC.

PMID- 8300444
TI  - Formation of vitamins by pure cultures of tempe moulds and bacteria during the
      tempe solid substrate fermentation.
AB  - The formation of water soluble vitamins (vitamin B12, vitamin B6, riboflavin,
      thiamine, nicotinic acid and nicotinamide) during the tempe solid substrate
      fermentation was investigated. The role of several strains of Rhizopus
      oligosporus, R. arrhizus, and R. stolonifer and the role of several bacteria in
      the vitamin formation process were checked. All fungal and bacterial strains were
      isolated from Indonesian tempe and soaking water samples. The Rhizopus strains
      formed riboflavin, nicotinic acid, nicotinamide and vitamin B6. The final
      concentrations of these substances depended on the different strains involved and
      on the fermentation time. Isolates of R. oligosporus were generally the best
      vitamin formers. The moulds did not produce physiologically active vitamin B12.
      The thiamine content decreased during fermentation. The addition of bacteria,
      which had been selected in a screening for vitamin B12 production, resulted in an
      increase of physiologically active vitamin B12. Citrobacter freundii and
      Klebsiella pneumoniae showed the best formation capabilities. Furthermore, the
      bacteria produced riboflavin and vitamin B6 in addition to the moulds. The
      influence of Rhizopus on the vitamin B12 formation of Cit. freundii was also
      investigated. The vitamin content of tempe that was fermented with the mould and
      the bacterium was three times as high as a control fermentation with Cit.
      freundii only.

PMID- 8300445
TI  - Characterization of Salmonella virchow phage types by plasmid profile and IS200
      distribution.
AB  - The type strains of the 57 phage types of Salmonella virchow have been
      characterized by plasmid profile and by distribution of the insertion sequence
      IS200. Thirty-two strains carried plasmids and 21 profile types were identified;
      17 strains were resistant to antimicrobial agents. In contrast only six of the
      type strains carried IS200 elements and three patterns were identified. Within
      Salm. virchow phage type 31, five of 10 wild-type isolates carried plasmids and
      two plasmid profiles were identified; in contrast, an IS200 element was
      identified in the genome of only one of these strains. It is concluded that for
      Salm. virchow, IS200 is unlikely to significantly extend the degree of
      discrimination achieved by phage typing which may be supplemented when
      appropriate by plasmid profile typing.

PMID- 8300446
TI  - A study of the use of rapid methods for preservative efficacy testing of
      pharmaceuticals and cosmetics.
AB  - Three rapid microbiological methods, impedance, the direct epifluorescence
      technique (DEFT-MEM) and ATP bioluminescence (ATP-B) were evaluated for their
      applicability to preservative efficacy testing (PET) of pharmaceuticals and
      cosmetics. A good correlation between rapid method response and total colony
      counts was obtained for untreated suspensions of Staphylococcus aureus,
      Pseudomonas aeruginosa and Candida albicans with all three methods but, for
      Aspergillus niger, with impedance only. For chlorhexidine-treated suspensions of
      Staph. Aureus and C. albicans, a good dose-response curve was obtained with
      impedance, but ATP-B and DEFT-MEM methods underestimated the kill by the order of
      1-6 logs. From the results of this study it is concluded that impedance offers an
      alternative method to colony counting methods for PET but, at their present level
      of method development, neither DEFT-MEM nor ATP-B can be considered as
      satisfactory.

PMID- 8300447
TI  - The development and assessment of DNA and oligonucleotide probes for the specific
      detection of Bacillus anthracis.
AB  - Two DNA probes and a number of oligonucleotide probes were designed from the
      virulence factor genes of Bacillus anthracis. These probes were tested for
      specificity against 52 B. anthracis strains and 233 Bacillus strains encompassing
      23 other species. A rapid slot blotting technique was used for screening the
      large numbers of isolates involved. All probes tested appeared to be specific for
      B. anthracis under high stringency conditions. These probes could differentiate
      between virulent and avirulent strains. The probes were also applied to the
      detection of B. anthracis in routine environmental and clinical samples. A non
      radioactive hybridization and detection system based on digoxigenin-11-dUTP was
      developed.

PMID- 8300448
TI  - The effects of medium and rate of freezing on the survival of chlamydias after
      lyophilization.
AB  - The effects of suspension media and rate of freezing on the survival of Chlamydia
      trachomatis LGV2 and Chlamydia pneumoniae after lyophilization were assessed. The
      highest loss in infectious elementary bodies (EBs) occurred during
      lyophilization. The survival was higher after freezing at a rate of 1 degree C
      min-1 and lyophilization than that after rapid freezing at -70 degrees C or -196
      degrees C. The recovery (+/- 5%) was higher when fetal calf serum (FCS)
      containing glucose, saccharose or lactose were used as lyophilization media than
      that (0.5-3%) when yolk-sac, skimmed milk or phosphate buffer containing sucrose,
      glutamine and 10% FCS (SPG) were used. After lyophilization, the survival was not
      affected in the tested range from 10(4) to 5 x 10(6) inclusion-forming units
      (ifu) ml-1 prior to freezing. After storage for 4 months at 4 degrees C, the
      numbers of ifu of both Chlamydia serovars that were recovered were identical to
      the numbers of ifu immediately after lyophilization. It was concluded that
      chlamydias can be stored and transported in lyophilized form. However, a loss of
      95% in infectious EBs should be taken into account.

PMID- 8300449
TI  - Role of cell-binding in the antibacterial mechanism of lactoferricin B.
AB  - The antibacterial cell-binding properties of lactoferricin B, a potent
      bactericidal peptide derived from bovine lactoferrin, were investigated for the
      first time. To facilitate measurements of binding the peptide was radiolabelled
      by reduction and treatment with iodo-[1-14C]acetamide. 14C-lactoferricin B bound
      rapidly to the surface of Escherichia coli and Bacillus subtilis. The rate of
      binding was consistent with the rapid rate of killing caused by this peptide. The
      extent of binding was reduced in the presence of Mg2+ or Ca2+ ions which act to
      reduce its antimicrobial effectiveness. The optimal pH for binding was strain
      dependent and the killing effect was maximal near the optimal pH for cell binding
      with each strain tested. These observations indicate that direct interaction of
      lactoferricin B with the cell surface is necessary for its lethal effect. The
      number of peptide molecules bound (> 10(6) per cell) was more than would be
      expected for binding to specific protein receptors. Lactoferricin B inhibited
      bacterial uptake of 3H-proline with effectiveness similar to polymyxin B, a known
      membrane-disruptive agent. The cell-binding event appears to lead to a disruption
      of normal permeability functions of the cytoplasmic membrane.

PMID- 8300450
TI  - Identification and typing of Proteus penneri and Proteus vulgaris biogroups 2 and
      3, from clinical sources, by computerized analysis of electrophoretic protein
      patterns.
AB  - Seventy-six strains of the Proteus vulgaris complex (Pr. penneri and Pr. vulgaris
      biogroups 2 and 3) were characterized by one-dimensional SDS-PAGE of cellular
      proteins. The protein patterns were highly reproducible. The strains came from
      various countries and were mainly of human origin: urine (28), respiratory tract
      (13), wounds (8), faeces (7), blood (3), miscellaneous sources (6) and unknown
      sources (11). The patterns of these strains, together with those of the type
      strains of seven Morganella, Proteus and Providencia species were subjected to
      two numerical analyses. In the first, in which the principal protein bands (in
      the 35.0-42.0 kDa range) were excluded, the strains of the Pr. vulgaris complex
      formed four clusters at the 83% similarity level. These corresponded to Pr.
      penneri, Pr. vulgaris biogroup 2, and two clusters (3a and 3b) represented
      biogroup 3. Each of these clusters was distinct from the Morganella, Proteus and
      Providencia reference strains. In the second analysis, which included all the
      protein bands, the 41 Pr. penneri strains showed little heterogeneity but 17
      subphenons could be recognized among the 35 strains of Pr. vulgaris biogroups 2
      and 3. These results support the division of biogroup 3 strains into at least two
      separate taxa. Other results indicate that biogroup 3 is heterogeneous and may
      contain further genomic groups. The method also provides a basis for typing
      clinical strains of Pr. vulgaris biogroups 2 and 3.

PMID- 8300451
TI  - Rationale of angioplasty in chronic total coronary occlusion.

PMID- 8300452
TI  - Minimal change nephrotic syndrome.

PMID- 8300453
TI  - Primary hyperaldosteronism.

PMID- 8300454
TI  - Natural history and response to treatment of minimal change nephrotic syndrome.
AB  - This study is a retrospective analysis of 177 patients of minimal change
      nephrotic syndrome seen between 1985 and 1989. Fifty nine of these had renal
      biopsy done and the others were diagnosed on clinical grounds. Short courses of
      prednisolone were used for three episodes in one year. If a fourth episode
      occurred in any 12 month period, cyclophosphamide was started. This was needed in
      26 patients and was also used in 9 patients who did not respond to 8 weeks of
      prednisolone. Follow up ranged from 4 months to 5 years (mean 1.4 years). Thirty
      nine percent of patients sustained remission after the first course of steroids.
      Histological variations (presence or absence of diffuse mesangial proliferation
      or IgM deposits) and age made no difference to the response to treatment and
      subsequent relapses.

PMID- 8300455
TI  - Primary hyperaldosteronism--diagnostic approach and management.
AB  - Primary hyperaldosteronism was detected in 1% of patients evaluated for secondary
      hypertension in a referral hospital in Southern India. The presence of
      hypokalemia with inappropriate kaliuresis (24 hr. urine K > 20mEq) was an
      important diagnostic clue. High resolution CT scans were found to be useful for
      localising the tumour. Preoperatively nifedipine and spironolactone were employed
      to correct hypertension and hypokalemia. The same drugs were also found to be
      excellent for long-term control of hypertension and hypokalemia in patients who
      had bilateral adrenal hyperplasia and aldosteronism.

PMID- 8300456
TI  - Effect of vasodilator therapy on mortality in chronic congestive heart failure.
AB  - We compared the effects of Hydralazine and Isosorbide dinitrate (ISDN) with those
      of an angiotensin-converting-enzyme inhibitor, captopril on mortality in patients
      with chronic congestive heart failure (NYHA class III and IV). Patients receiving
      conventional treatment with digoxin and diuretics were randomly assigned to
      receive either placebo (n = 51), hydralazine-ISDN. (n = 50) or captopril (n = 52)
      in a double blind trial. At the end of 6 months there were 14 deaths in the
      placebo group (27.4%) as compared with 11 deaths in the hydralazine-ISDN group
      (22%)--a mortality reduction of 20% (P > 0.05) and 10 deaths in the captopril
      group (19.2%)--a mortality reduction of 30% (p > 0.05). At the end of one year,
      mortality was 50%, 42% and 30% in the placebo, hydralazine-ISDN and captopril
      groups respectively with a mortality reduction of 16% in the hydralazine-ISDN
      group (p > 0.05) and 40% in the captopril group (p < 0.05) compared to the
      placebo group. The mortality reduction was mainly due to reduction in deaths
      attributed to progressive heart failure. The data suggests that the addition of
      captopril to conventional treatment significantly reduces mortality in patients
      with severe congestive heart failure. Hydralazine-isorobide dinitrate also
      reduced mortality but statistically this was not significant.

PMID- 8300457
TI  - Left ventricular diastolic function--pulsed Doppler echocardiography versus
      radionuclide angiography.
AB  - Fifty five consecutive patients diagnosed to have coronary artery disease by
      coronary angiography had their left ventricular (LV) diastolic functions
      evaluated by pulsed doppler (PD) methods and radionuclide angiography (RNA).
      Using PD, the peak velocities of the early filling wave 'E' and the late filling
      wave 'A' of mitral inflow were measured. LV diastolic dysfunction, defined as E/A
      ratio less than 1.0, was present in 31 of 38 patients with low RNA peak filling
      rates (PFR) of 2.3 EDV/sec or less (sensitivity 81.6%). Normal E/A ratios (> 1.0)
      were seen in 13 of 17 patients with normal RNA PFR of > 2.3 EDV/sec (specificity
      76.5%). Both methods were in agreement in 44 of 55 patients (accuracy 80%). There
      was good direct correlation between RNA PFR and PD E/A ratio (correlation
      coefficient r = 0.51, P < 0.01). It is concluded that PD echocardiography is a
      simple and reliable method of identifying diastolic dysfunction in patients with
      ischaemic heart disease.

PMID- 8300458
TI  - Percutaneous transluminal coronary angioplasty in totally occluded arteries.
AB  - Out of 321 consecutive cases of Percutaneous Transluminal Coronary Angioplasty
      (PTCA), 28 (8.7%) patients underwent PTCA for nonacute total occlusion with no
      visible antegrade flow. All patients had evidence of reversible ischaemia in the
      territory of totally occluded artery. Overall initial success rate was 66% and
      was mainly related to the duration of the occlusion (85% for occlusion of 1 month
      or less, 70% for 1-6 months, and nil for more than 6 months duration). In 21
      (75%) cases where collateral circulation to the occluded vessel could be
      demonstrated before PTCA, was not visible after successful PTCA. Failure was
      mainly due to inability to cross the lesion with the guide wire (8 out of 10
      failures). Emergency Coronary Artery Bypass Graft (CABG) surgery was required in
      2 cases where dissection of nontarget vessels occurred during manipulation of the
      guide wire. Acute reocclusion occurred in 2 cases, both were redilated
      successfully. There was no death. Although the primary success rate is lower than
      that associated with conventional stenotic lesions, with improvement in the
      hardware-balloon catheters and guide wires, coronary angioplasty can be performed
      successfully in majority of the patients with total coronary occlusion.

PMID- 8300459
TI  - Herpes simplex encephalitis: a diagnostic and therapeutic reapprisal.
AB  - Herpes Simplex Encephalitis (HSE) appears to be underdiagnosed in India, though
      viral encephalitides constitutes an important entity with significant morbidity.
      With an upsurge in AIDS, HSE may perhaps emerge as an important opportunistic
      infection in future. We discuss the clinical features and laboratory evaluation
      of nine cases of HSE seen in the last 12 years at our center. Diagnosis was
      established by brain biopsy in one, virological studies in six and at autopsy in
      three. Immunocytochemically viral antigens could be localized in 4
      biopsied/autopsied brain tissue and in CSF cells on a cytospin preparation in
      one. This has facilitated rapid diagnosis in our cases. Virus isolation was
      successful in two. Three subjects were treated with acyclovir and all survived
      with variable morbidity. Four patients expired and none of them had received any
      specific antiviral drugs. Rapid diagnosis and early treatment with acyclovir has
      been highlighted.

PMID- 8300460
TI  - Effect of calcium channel antagonists on cholinergic bronchial responsiveness in
      asthma.
AB  - Bronchial responsiveness to methacholine was studied in 23 stable asthmatics
      before and after nifedipine and diltiazem. There was no significant
      bronchodilatory effect of either calcium channel antagonists. The mean
      provocative dose of methacholine required to produce a 20% fall in FEV1 (PC20 =
      0.157 +/- 0.74 mg) was not altered by nifedipine (PC20 = 0.159 +/- 0.61).
      However, diltiazem offered significant protection. The mean ratio of PC20 after
      diltiazem over baseline was 3.27 +/- 3.55. The results suggest that although both
      calcium channel antagonists have no influence on normal basal bronchomotor tone,
      diltiazem does significantly protect against cholinergic stimulation.

PMID- 8300461
TI  - Anti-inflammatory action of steroid inhalers.
AB  - With mucosal inflammation contributing to the pathogenesis of asthma, it is
      increasingly accepted that long term steroid inhalers may induce remission in
      chronic long standing asthmatics. The present study involved 44 stable asthmatics
      who were randomly given either beclomethasone dipropionate inhaler (50 ug) 2
      puffs qds or salbutamol inhaler (100 mcg) 2 puffs tds in addition to their oral
      bronchodilators. Pulmonary function testing, bronchoalveolar lavage and complete
      blood count were done at basal and weekly intervals and at the end of the study.
      The absolute eosinophil count showed a significant drop in the beclomethasone
      group as compared to the salbutamol group. Serial lung functions showed a
      significant improvement in the pre-bronchodilator PEFR and the pre-bronchodilator
      FVC in the beclomethasone group as compared to the salbutamol group. There was no
      significant change in the lavage eosinophil count pre and post-bronchodilator in
      both groups. Steroid inhalers are thus useful in long term management of
      bronchial asthma especially with respect to reducing bronchodilator requirement.

PMID- 8300462
TI  - An easy method of spirometry.
AB  - Recording of forced expiration from tidal inspiratory level-referred to as Forced
      Expiratory Capacity (FEC) is a simple and more convenient technique than the
      conventional forced vital capacity (FVC) manouvre. From FEC tracing, volume
      expelled in one second (FEC1) and its percentage (FEC1%) can be measured. Such
      spirometric recording obtained from tidal breathing to Residual Volume (RV) may
      be referred to as Spirometric Recording at low lung volume. Asthmatics as well as
      old subjects find this manouvre easier to perform than the conventional FVC
      technique. FEC recording becomes a simple, reliable and sensitive test for
      evaluation of early airway obstruction in asymptomatic smokers and therefore may
      be utilised in clinical and epidemiologic surveys.

PMID- 8300463
TI  - Neurocysticercosis.
AB  - Sixty-two cases of neurocysticercosis (NCC) were examined over a period of five
      years. Convulsive seizure was the commonest presentation (57%). The other modes
      of presentation included features of raised intracranial pressure (19%)
      meningoencephalitis (9%), "Stroke" like onset (4%) and progressive dementia (6%).
      Clinical signs were scanty. Six patients had papilloedema, five had hemiparesis
      while three had isolated cranial nerve palsies. Soft tissue calcification and
      mucocutaneous nodules were infrequent and was found in 13 (21%) and 5 cases (8%)
      respectively. Clinical suspicion supported by CT scan and Immunobiologic tests
      using ELISA were the mainstay in diagnosis. Praziquantel and Albendazole were
      found effective in the treatment of neurocysticercosis, but because of serious
      side effects encountered in some cases, the drugs should be used cautiously in
      selected cases only.

PMID- 8300464
TI  - Effect of atenolol and labetalol on serum lipids.
AB  - Adverse alterations in lipid profile suggesting higher atherogenicity were
      observed following 12 weeks treatment with atenolol in patients of hypertension.
      No significant alterations in lipid profile were observed with labetalol therapy.

PMID- 8300465
TI  - Acute promyelocytic leukemia with ischaemic events.

PMID- 8300466
TI  - Desquamative interstitial pneumonia.
AB  - A rare case of Desquamative Interstitial pneumonia confirmed by open lung biopsy,
      is reported. The course was marked by development of spontaneous pneumothorax and
      failure to respond to steroids.

PMID- 8300467
TI  - Adult thoracic ganglioneuroblastoma with massive pleural effusion.

PMID- 8300468
TI  - Myocardial calcification and left ventricular aneurysm in chronic myeloid
      leukaemia.

PMID- 8300469
TI  - Stroke following scorpion sting.
AB  - A 30 year old male presented with crossed buccofacial apraxia, apraxia for
      speech, Left UMN facial palsy and hemiplegia following scorpion sting. A
      cerebrovascular accident can develop following a scorpion sting due to venom
      induced cerebral thrombosis.

PMID- 8300470
TI  - Pancytopenia--a rare presentation of miliary tuberculosis.

PMID- 8300471
TI  - "Prolymphocytoid" transformation of chronic lymphocytic leukemia.

PMID- 8300472
TI  - Carpal tunnel syndrome with propranolol.

PMID- 8300473
TI  - Cost effectiveness of drug therapy in enteric fever.

PMID- 8300475
TI  - El Tor cholera in India.

PMID- 8300474
TI  - Fresh frozen plasma instead of higher than conventional dose of antivenom in
      viper envenoming.

PMID- 8300476
TI  - Tropical medicine as a subspeciality--its relevance in India.

PMID- 8300477
TI  - Acute renal failure secondary to myoglobinuria.

PMID- 8300478
TI  - Exacerbation of myasthenia gravis by single dose of Respren (Ethnor) and
      Astemizole tablets.

PMID- 8300479
TI  - Transdermal antihypertensive for elderly hypertensives.

PMID- 8300480
TI  - Lipids, atherosclerosis and risk factors.

PMID- 8300481
TI  - Thyroid hormones in diabetic ketoacidosis.

PMID- 8300482
TI  - Plasma lipoproteins in cortical and lacunar infarction.
AB  - Plasma lipoproteins in 30 patients of cortical infarction and 20 patients of
      lacunar infarction were estimated to study the relation of plasma lipids to the
      risk for ischaemic stroke by comparing clinical and biochemical characteristics
      of survivors. No significant differences were observed in the concentrations of
      total cholesterol, triglycerides, low density lipoproteins, very low density
      lipoproteins in both the groups. However patients with lacunar infarction had
      higher concentrations of high density lipoproteins as compared to patients with
      cortical infarction. These data suggest that previously demonstrated differences
      in HDL concentration between patients with ischaemic stroke and control subjects
      without stroke may be true for patients with cortical infarction but not for
      patients of lacunar infarction.

PMID- 8300483
TI  - Thyroid hormones in diabetic ketoacidosis before and after therapy.
AB  - Fifteen IDDM patients were evaluated for thyroid hormone abnormalities before and
      after control of diabetes mellitus/ketoacidosis. Blood sugar mean +/- SEM mg/dl
      on admission was 430 +/- 20.3 and after therapy fasting and post prandial blood
      sugar values were 120 +/- 14.5 and 150 +/- 20.2 respectively. GHb mean +/- SEM %
      on admission was 15.2 +/- 0.36. Serum T3 mean +/- SEM ng/dl of 0.36 +/- 0.04 was
      in hypothyroid range and rT3 mean +/- SEM ng/ml 0.40 +/- 0.6 was significantly
      raised (P < 0.001) before therapy. After metabolic control both T3 and rT3 became
      normal. T4 concentration mean +/- SEM meg/dl of 5.5 +/- 0.7 was well within
      normal range before therapy and rose to mean +/- SEM mcg/dl 8.8 +/- 0.5 after
      therapy (P < 0.01). TSH response to TRH was blunted in uncontrolled state. It is
      concluded that peripheral changes in T3, T4 and rT3 (low T3, high rT3 and low or
      normal T4) occurred in uncontrolled diabetic state during ketoacidosis. TSH
      response to TRH was blunted due to suppression of hypothalamic pituitary thyroid
      axis which takes more than a week for complete recovery.

PMID- 8300484
TI  - Serum immunoglobulins in sickle cell disease.
AB  - Immunoglobulins IgG, IgA and IgM were estimated in 20 cases of sickle cell
      disease in steady state, eleven cases of sickle cell disease in crisis and/or
      infection, 20 cases of sickle cell trait and 14 normal healthy controls.
      Immunoglobulin deficiency has not been observed in sickle cell disease.
      Significantly raised IgG but normal IgA and IgM found in sickle cell disease
      cases was probably due to chronic stimulation of reticuloendothelial cells
      secondary to chronic hemolysis. IgM levels were significantly higher in patients
      with splenic enlargement > 3 cm. There was no alteration in immunoglobulin levels
      in sickle cell trait.

PMID- 8300485
TI  - Prognostic significance of radiographic cardiomegaly in patients with coronary
      heart disease.
AB  - To define the long term prognosis in patients with coronary heart disease (CHD)
      we have used criteria of radiographic cardiomegaly supplemented by M-mode
      echocardiography. 74 patients (Group A) with CHD and cardiomegaly were seen from
      1980 to 1983 and have been compared to 121 patients (Group B) with normal cardiac
      size and prior myocardial infarction. Patients in Group A were defined by
      radiographic cardiomegaly with cardio-thoracic ratio of 0.50 or more. The groups
      were matched for age, sex and major coronary risk factors like hypertension,
      total cholesterol levels, smoking and diabetes. The echocardiographic diastolic
      left ventricular internal dimension of 6.16 +/- 0.34 cm was significantly more in
      Group A as compared to 4.94 +/- 0.26 cm in Group B (t = 2.03, p < 0.05).
      Actuarial analysis indicates that mortality or surgical option is significantly
      higher in patients with cardiomegaly (Logrank test = 59.72, p < 0.001) and the
      mortality is significantly more during the initial years. Thus, radiographic
      cardiomegaly indicates a bad prognosis in patients with CHD.

PMID- 8300486
TI  - The prevalence of hypertension in rural population around Sevagram.
AB  - To detect the prevalence of hypertension in an asymptomatic rural community from
      Central India, we screened 4045 subjects (2247 men and 1798 women) aged 20 and
      beyond. The prevalence of hypertension was 34.12 per thousand population, being
      higher in women (40.60 per thousand) than in men (28.92 per thousand). Level of
      physical activity, economic status, smoking and body mass index showed real
      association with hypertension.

PMID- 8300487
TI  - Effect of aerosolised verapamil and nifedipine in bronchial asthma.
AB  - Twenty patients of bronchial asthma were given 5 mg of either nifedipine or
      verapamil as aerosol therapy in a randomized fashion. Both drugs showed a
      statistically significant improvement in FVC, PEFR at zero hours lasting through
      90-120 minutes. Changes in respiratory rate, pulse rate, blood pressure were
      insignificant with verapamil while appreciable tachycardia and transient fall in
      BP occurred with nifedipine therapy.

PMID- 8300488
TI  - Short course ciprofloxacin therapy for enteric fever.
AB  - A short course of ciprofloxacin, 750 mgm b.i.d. for 7 days was found to be
      effective in the treatment of enteric fever in 21 hospitalized patients with
      S.typhi (18) and S.paratyphi A(3). Median time for fever response was 3 days. All
      isolates were susceptible to ciprofloxacin (MIC 0.0078-0.062 mcgm/ml). The mean
      serum peak and trough levels were 5.4 and 1.6 mcgm/ml respectively. Stool
      cultures were free of Salmonellae on follow up (11-24 weeks). Two developed
      recurrence of paratyphoid fever, 17 days and 4 months after therapy.

PMID- 8300489
TI  - Compliance monitoring in epileptic patients.
AB  - Poor patient compliance is one of the major causes of non responsiveness to
      antiepileptic drug therapy. Compliance is mostly assessed by self reporting, pill
      counting and plasma drug level estimation. However, none of them is fool proof.
      Subtherapeutic plasma drug levels can be due to poor compliance or need for
      higher dosage. Therefore, in the present study, 20 adult non responsive epileptic
      patients showing subtherapeutic plasma phenytoin levels inspite of receiving
      standard phenytoin therapy and history of good compliance were admitted in the
      clinical pharmacology ward and received supervised drug treatment for five days
      after which plasma phenytoin levels in 14 patients increased to therapeutic
      range. All except one (i.e. 9 out of 10) patients showing phenytoin levels < 5
      ug/ml inspite of phenytoin dosage of > 300 mg/d and history of good compliance
      were found to be noncompliant. Hence adult patient receiving greater than or
      equal to 300 mg/day phenytion and showing phenytoin levels less than or equal to
      5 ug/ml should be investigated for possible noncompliance before altering their
      dosage schedules.

PMID- 8300490
TI  - Magnesium in cardiovascular therapy.

PMID- 8300491
TI  - Hydatid disease of the liver--non surgical options.

PMID- 8300492
TI  - Hypertension in diabetes mellitus.

PMID- 8300493
TI  - An unusual presentation of a pheochromocytoma.

PMID- 8300494
TI  - Rathke's cleft cyst.

PMID- 8300495
TI  - Acute myositis complicated by myoglobinuric acute renal failure.

PMID- 8300496
TI  - An unusual case of heavy metal poisoning.

PMID- 8300497
TI  - Waldenstrom's macroglobulinemia--a case with lymphocytosis.

PMID- 8300498
TI  - Cranial nerve palsy at high altitude.

PMID- 8300499
TI  - Probable case of neurosarcoidosis.

PMID- 8300500
TI  - Hemangioblastoma of the brain stem presenting as hypertension.

PMID- 8300501
TI  - Primary extranodal non-Hodgkins lymphoma of the palate.

PMID- 8300502
TI  - Chung-Strauss syndrome.

PMID- 8300503
TI  - Infective endocarditis in a case of systemic lupus erythematosus.

PMID- 8300504
TI  - Oral typhoid vaccine.

PMID- 8300505
TI  - Infections in acute leukemia.

PMID- 8300506
TI  - Sternal tuberculosis in combination with thalassmia.

PMID- 8300507
TI  - Paroxysmal nocturnal hemoglobulinuria.

PMID- 8300508
TI  - Meige's syndrome.

PMID- 8300509
TI  - Puerperal cortical venous thrombosis.

PMID- 8300511
TI  - Selection of functional signal peptide cleavage sites from a library of random
      sequences.
AB  - The export of proteins to the periplasmic compartment of bacterial cells is
      mediated by an amino-terminal signal peptide. After transport, the signal peptide
      is cleaved by a processing enzyme, signal peptidase I. A comparison of the
      cleavage sites of many exported proteins has identified a conserved feature of
      small, uncharged amino acids at positions -1 and -3 relative to the cleavage
      site. To determine experimentally the sequences required for efficient signal
      peptide cleavage, we simultaneously randomized the amino acid residues from
      positions -4 to +2 of the TEM-1 beta-lactamase enzyme to form a library of random
      sequences. Mutants that provide wild-type levels of ampicillin resistance were
      then selected from the random-sequence library. The sequences of 15 mutants
      indicated a bias towards small amino acids. The N-terminal amino acid sequence of
      the mature enzyme was determined for nine of the mutants to assign the new -1 and
      -3 residues. Alanine was present in the -1 position for all nine of these
      mutants, strongly supporting the importance of alanine at the -1 position. The
      amino acids at the -3 position were much less conserved but were consistent with
      the -3 rules derived from sequence comparisons. Compared with the wild type, two
      of the nine mutants have an altered cleavage position, suggesting that sequence
      is more important than position for processing of the signal peptide.

PMID- 8300510
TI  - Genetic rearrangement associated with in vivo mucoid conversion of Pseudomonas
      aeruginosa PAO is due to insertion elements.
AB  - The conversion of Pseudomonas aeruginosa PAO to the mucoid phenotype has been
      reported for a chronic pulmonary infection model in rats (D. E. Woods, P. A.
      Sokol, L. E. Bryan, D. G. Storey, S. J. Mattingly, H. J. Vogel, and H. Ceri, J.
      Infect. Dis. 163:143-149, 1991). This conversion was associated with a genetic
      rearrangement upstream of the exotoxin A gene. To characterize the genetic
      rearrangement, the region upstream of the toxA gene was cloned from PAO, PAO-muc
      (a mucoid strain), and PAO-rev (a nonmucoid revertant strain). The nucleotide
      sequence of a 4.8-kb fragment from PAO-muc was determined. A+T-rich regions of
      approximately 2 kb (IS-PA-4) and 0.4 kb (IS-PA-5) were identified in this
      fragment. DNA probes constructed internal to these regions hybridized to PAO-muc
      but not to PAO or PAO-rev, suggesting that PAO-muc contains an insertion element.
      Sequence analysis of the nonmucoid clones indicated that a 2,561-bp fragment
      corresponding to IS-PA-4 and a 992-bp fragment corresponding to IS-PA-5 were not
      present in PAO or PAO-rev. Both nonmucoid clones, however, contained in the same
      location as IS-PA-4, a 1,313-bp region which was not present in PAO-muc. DNA
      probes complementary to this sequence, designated IS-PA-6, did not hybridize with
      PAO-muc, indicating that this sequence had been replaced upon conversion to the
      mucoid phenotype. Between IS-PA-4 and IS-PA-5 there was a 500-bp sequence which
      was 94% identical to the 500-bp sequence downstream of IS-PA-6. These insertion
      elements had some DNA sequence similarity to plasmid and transposon sequences,
      suggesting that they may be of plasmid origin. IS-PA-4 and IS-PA-5 were shown
      also to be present in two mucoid isolates from cystic fibrosis patients. The
      insertions occurred in the same location upstream of the toxA gene, suggesting
      that this type of genetic recombination may also be associated with mucoid
      conversion in some P. aeruginosa clinical isolates.

PMID- 8300513
TI  - Regulation of the Bacillus anthracis protective antigen gene: CO2 and a trans
      acting element activate transcription from one of two promoters.
AB  - The pag gene of Bacillus anthracis, located on plasmid pXO1 (185 kb), encodes
      protective antigen, a component of the anthrax lethal and edema toxins. Synthesis
      of protective antigen is enhanced during growth of the organism with elevated
      levels of CO2. The CO2 effect is at the level of transcription, and pXO1-encoded
      regulatory factors have been implicated in control of pag expression. We used a
      Tn917-LTV3 insertion mutant of B. anthracis in which the wild-type pag gene on
      pXO1 was replaced with a pag-lacZ transcriptional fusion to monitor pag promoter
      activity. Expression of the pag-lacZ fusion is induced five- to eightfold during
      growth in 5% CO2 compared with growth in air. Growth in 20% CO2 increases
      transcription up to 19-fold. By monitoring pag-lacZ expression in atmospheres
      with different O2 and CO2 concentrations, we demonstrated definitively that the
      CO2 effect is specific and not simply a result of increased anaerobiosis. The
      results of 5' end mapping of pag transcripts indicate multiple sites of
      transcript initiation. We have determined two major apparent start sites,
      designated P1 and P2, located at positions -58 and -26 relative to the
      translation initiation codon, respectively. Analysis of total RNA from late-log
      phase cells shows comparable initiation from P1 and P2 in wild-type strains grown
      in aerobic conditions. However, initiation from P1 is increased approximately 10
      fold in cultures grown with an elevated level (5%) of CO2. We have identified a
      locus on pXO1, more than 13 kb upstream from the pag gene, which enhances pag
      transcription. When added in trans, this locus increases the level of transcripts
      with 5' ends mapping to P1 but has no effect on the level of transcripts with 5'
      ends mapping to P2. The CO2 effect on P1 is observed only in the presence of the
      activator locus.

PMID- 8300512
TI  - A low-Ca2+ response (LCR) secretion (ysc) locus lies within the lcrB region of
      the LCR plasmid in Yersinia pestis.
AB  - The causative agent of plague, Yersinia pestis, contains a 75-kb plasmid, pCD1,
      which carries a virulence-related stimulon called the low-Ca2+ response stimulon
      (LCRS). LCRS operons are regulated by the environmental signals of temperature
      and Ca2+. This study characterized a portion of the lcrB region of pCD1, known to
      contain at least one gene necessary for the regulation of LCRS operons by Ca2+.
      The sequence of a 2-kb region revealed three open reading frames, designated
      yscQ, yscR, and yscS, predicted to encode acidic proteins of 34.4, 24.4, and 8.5
      kDa. All three proteins were homologous to proteins involved in flagellar
      function or virulence. An antipeptide antibody specific for YscR was used to
      localize YscR to the inner membrane of Y. pestis. Analysis of yscR-phoA fusions
      supported a model for yscR which predicts four transmembrane regions and a large,
      central hydrophilic domain. In-frame deletion mutations of yscQ and yscR were
      constructed and moved into Y. pestis. Both mutants failed to show the restriction
      of growth that normally accompanies maximal LCRS induction. Unlike the parent Y.
      pestis, the yscR mutant did not respond to the absence of Ca2+ by increasing the
      net transcription or translation of the LCRS-encoded V antigen, YopM, or LcrG.
      The yscR mutant also was defective for secretion of V antigen, YopM, and LcrG.
      These findings implicate a dual role for YscR in regulation of LCRS operons and
      secretion of LCRS proteins and add to the developing picture of how secretion of
      virulence proteins may be coupled to transcriptional regulation in yersiniae.

PMID- 8300514
TI  - Lactobacillus plantarum ldhL gene: overexpression and deletion.
AB  - Lactobacillus plantarum is a lactic acid bacterium that converts pyruvate to L
      (+)- and D-(-)-lactate with stereospecific enzymes designated L-(+)- and D-(-)
      lactate dehydrogenase (LDH), respectively. A gene (designated ldhL) that encodes
      L-(+)-lactate dehydrogenase from L. plantarum DG301 was cloned by complementation
      in Escherichia coli. The nucleotide sequence of the ldhL gene predicted a protein
      of 320 amino acids closely related to that of Lactobacillus pentosus. A multicopy
      plasmid bearing the ldhL gene without modification of its expression signals was
      introduced in L. plantarum. L-LDH activity was increased up to 13-fold through
      this gene dosage effect. However, this change had hardly any effect on the
      production of L-(+)- and D-(-)-lactate. A stable chromosomal deletion in the ldhL
      gene was then constructed in L. plantarum by a two-step homologous recombination
      process. Inactivation of the gene resulted in the absence of L-LDH activity and
      in exclusive production of the D isomer of lactate. However, the global
      concentration of lactate in the culture supernatant remained unchanged.

PMID- 8300515
TI  - The Rhodobacter sphaeroides cytochrome c2 signal peptide is not necessary for
      export and heme attachment.
AB  - Rhodobacter sphaeroides cytochrome c2 (cyt c2) is a member of the heme-containing
      cytochrome c protein family that is found in the periplasmic space of this gram
      negative bacterium. This exported polypeptide is made as a higher-molecular
      weight precursor with a typical procaryotic signal peptide. Therefore, cyt c2
      maturation is normally expected to involve precursor translocation across the
      cytoplasmic membrane, cleavage of the signal peptide, and covalent heme
      attachment. Surprisingly, synthesis as a precursor polypeptide is not a
      prerequisite for cyt c2 maturation because deleting the entire signal peptide
      does not prevent export, heme attachment, or function. Although cytochrome levels
      were reduced about threefold in cells containing this mutant protein, steady
      state cyt c2 levels were significantly higher than those of other exported
      bacterial polypeptides which contain analogous signal peptide deletions. Thus,
      this mutant protein has the unique ability to be translocated across the
      cytoplasmic membrane in the absence of a signal peptide. The covalent association
      of heme with this mutant protein also suggests that the signal peptide is not
      required for ligand attachment to the polypeptide chain. These results have
      uncovered some novel aspects of bacterial c-type cytochrome biosynthesis.

PMID- 8300516
TI  - Mutations in a gene encoding a new Hsp70 suppress rapid DNA inversion and bgl
      activation, but not proU derepression, in hns-1 mutant Escherichia coli.
AB  - Mutations in hns, the gene encoding the nucleoid-associated protein H-NS, affect
      both the expression of many specific unlinked genes and the inversion rate of the
      DNA segment containing the pilA promoter in Escherichia coli. A second-site
      mutation, termed hscA1, compensated for the effect of an hns-1 mutant allele on
      the pilA promoter inversion rate and on activation of the bgl operon. The proU
      operon, induced in an hns-1 background, remained derepressed in an hns-1 hscA1
      strain and was induced at an intermediate level in an hns hscA1 strain. An
      insertion mutant allele, hscA2-cat, conferred the same partial hns-1 compensatory
      phenotype as the hscA1 allele. The hscA gene encoded a 66-kDa protein product
      that is a member of the Hsp70 protein class. The gene encoding this product is
      part of a bicistronic operon that is preceded by a possible sigma 32 promoter and
      also encodes a 21-kDa protein with significant homology to the DnaJ protein
      family. The mutation defining the hscA1 allele resulted in a phenylalanine
      substituting a conserved serine residue located in the ATP-binding region of
      other Hsp70 proteins.

PMID- 8300517
TI  - nodZ, a unique host-specific nodulation gene, is involved in the fucosylation of
      the lipooligosaccharide nodulation signal of Bradyrhizobium japonicum.
AB  - The nodulation genes of rhizobia are regulated by the nodD gene product in
      response to host-produced flavonoids and appear to encode enzymes involved in the
      production of a lipo-chitose signal molecule required for infection and nodule
      formation. We have identified the nodZ gene of Bradyrhizobium japonicum, whose
      product is required for the addition of a 2-O-methylfucose residue to the
      terminal reducing N-acetylglucosamine of the nodulation signal. This substitution
      is essential for the biological activity of this molecule. Mutations in nodZ
      result in defective nodulation of siratro. Surprisingly, although nodZ clearly
      codes for nodulation function, it is not regulated by NodD and, indeed, shows
      elevated expression in planta. Therefore, nodZ represents a unique nodulation
      gene that is not under the control of NodD and yet is essential for the synthesis
      of an active nodulation signal.

PMID- 8300518
TI  - 4-Hydroxybenzoate-coenzyme A ligase from Rhodopseudomonas palustris:
      purification, gene sequence, and role in anaerobic degradation.
AB  - Anaerobic metabolism of most aromatic acids is initiated by coenzyme A thioester
      formation. Rhodopseudomonas palustris grows well under anaerobic, phototrophic
      conditions with many aromatic acids, including benzoate and 4-hydroxybenzoate, as
      a carbon source. A coenzyme A ligase that reacts with 4-hydroxybenzoate was
      purified from 4-hydroxybenzoate-grown cells of R. palustris. This enzyme required
      MgATP, reduced coenzyme A, and 4-hydroxybenzoate, benzoate, or cyclohex-1,4
      dienecarboxylate for optimal activity but also used phosphopantetheine, cyclohex
      2,5-dienecarboxylate, and 4-fluorobenzoate at lower rates. The 4-hydroxybenzoate
      coenzyme A ligase differed in molecular characteristics from a previously
      described benzoate-coenzyme A ligase from R. palustris, and the two ligases did
      not cross-react immunologically. The gene encoding the 4-hydroxybenzoate enzyme
      was cloned and sequenced. The deduced gene product showed about 20% amino acid
      identity with bacterial coenzyme A ligases involved in aerobic degradation of
      aromatic acids. An R. palustris mutant carrying a disrupted 4-hydroxybenzoate
      coenzyme A ligase gene was unable to grow with 4-hydroxybenzoate under anaerobic
      conditions, indicating that the enzyme is essential for anaerobic degradation of
      this compound.

PMID- 8300519
TI  - Regulation of mannitol biosynthesis and degradation by Cryptococcus neoformans.
AB  - Cryptococcus neoformans, an encapsulated yeast that is an opportunistic pathogen
      of AIDS patients, produced and secreted mannitol when incubated with an
      appropriate carbon source. Glucose, fructose, and mannose were good growth
      substrates and were converted to mannitol. Maltose and xylose were good growth
      substrates but were not converted to mannitol. Cells of C. neoformans that were
      grown on a non-mannitol-generating carbon source, such as peptone or xylose, were
      able to convert glucose to mannitol only after a prolonged lag period in the
      presence of glucose. It was concluded that the enzymes of the mannitol
      biosynthetic pathway were not constitutively expressed but were induced in
      response to glucose or to a glucose metabolite. Enzymes required to catabolize
      mannitol, however, were constitutively expressed. The production of mannitol was
      inhibited by anaerobiosis, by the respiratory poison rotenone, and by
      polyethylenesulfonate, a specific inhibitor of fungal NADP-dependent
      dehydrogenases. When cells were incubated with deuterated glucose, the deuterium
      content of the mannitol produced was much lower than that of the glucose
      precursor, indicating that the glucose was diluted by an intracellular pool of an
      intermediate. We had previously shown that C. neoformans contains a large
      intracellular pool of glucose 6-phosphate, and we now conclude that this pool of
      glucose 6-phosphate is metabolically active.

PMID- 8300520
TI  - Biochemical and molecular characterization of the diphenol oxidase of
      Cryptococcus neoformans: identification as a laccase.
AB  - Melanin production is a major virulence factor for Cryptococcus neoformans, an
      organism causing life-threatening infections in an estimated 10% of AIDS
      patients. In order to characterize the events involved in melanin synthesis, an
      enzyme having diphenol oxidase activity was purified and its gene was cloned. The
      enzyme was purified as a glycosylated 75-kDa protein which migrated at 66 kDa on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis after deglycosylation
      by endoglycosidase F. Substrate specificity resembled that of a laccase in that
      it oxidized multiple diphenolic and diamino compounds. Dopamine was shown by mass
      spectroscopy to be oxidized to decarboxy dopachrome, an intermediate of melanin
      synthesis. The enzyme contained 4.1 +/- 0.1 mol of copper per mol. It resembled a
      laccase in its absorbance spectrum, containing a peak of 610 nm and the shoulder
      at 320 nm, corresponding to the absorbance of a type I and type III copper,
      respectively. The cloned gene of C. neoformans laccase (CNLAC1) contained a
      single open reading frame encoding a polypeptide 624 amino acids in length. The
      encoded polypeptide contained a presumptive leader sequence, on the basis of its
      relative hydrophobicity and by comparison of the sequence to that of the N
      terminal sequence of the purified enzyme. CNLAC1 also contained 14 introns
      ranging from 52 to 340 bases long. Transcriptional activity of CNLAC1 was found
      to be derepressed in the absence of glucose and to correspond to an increase in
      enzymatic activity.

PMID- 8300521
TI  - A new gene required for cellulose production and a gene encoding cellulolytic
      activity in Acetobacter xylinum are colocalized with the bcs operon.
AB  - Recently, it was shown that a cellulose-negative mutant (Cel1) of Acetobacter
      xylinum ATCC 23769 carried an insertion of an indigenous transposable element
      (IS1031A) about 500 bp upstream of the bcs operon, required for cellulose
      synthesis. Here we show that Cel1 can be complemented by wild-type DNA covering
      the insertion point. Nucleotide sequencing of this region revealed the presence
      of two open reading frames, ORF1 and ORF2. ORF2, which is disrupted by the
      IS1031A insertion in Cel1, potentially encodes the complementing function. ORF1
      encodes a protein (CMCax) with significant homology to previously described
      endoglucanases. A cloned DNA fragment containing ORF1 expressed a carboxymethyl
      cellulose-hydrolyzing activity in Escherichia coli. In A. xylinum, CMCax is
      secreted into the culture growth medium. The CMCax mature protein consists of 322
      amino acids and has a molecular mass of 35.6 kDa.

PMID- 8300522
TI  - Isolation of the hemF operon containing the gene for the Escherichia coli aerobic
      coproporphyrinogen III oxidase by in vivo complementation of a yeast HEM13
      mutant.
AB  - Coproporphyrinogen III oxidase, an enzyme involved in heme biosynthesis,
      catalyzes the oxidative decarboxylation of coproporphyrinogen III to form
      protoporphyrinogen IX. Genetic and biochemical studies suggested the presence of
      two different coproporphyrinogen III oxidases, one for aerobic and one for
      anaerobic conditions. Here we report the cloning of the hemF gene, encoding the
      aerobic coproporphyrinogen III oxidase from Escherichia coli, by functional
      complementation of a Saccharomyces cerevisiae HEM13 mutant. An open reading frame
      of 897 bp encoding a protein of 299 amino acids with a calculated molecular mass
      of 34.3 kDa was identified. Sequence comparisons revealed 43% amino acid sequence
      identity with the product of the S. cerevisiae HEM13 gene and 90% identity with
      the product of the recently cloned Salmonella typhimurium hemF gene, while a
      structural relationship to the proposed anaerobic enzyme from Rhodobacter
      sphaeroides was not obvious. The hemF gene is in an operon with an upstream open
      reading frame (orf1) encoding a 31.7-kDa protein with homology to an amidase
      involved in cell wall metabolism. The hemF gene was mapped to 52.6 min of the E.
      coli chromosome. Primer extension experiments revealed a strong transcription
      initiation site upstream of orf1. A weak signal, possibly indicative of a second
      promoter, was also identified just upstream of the hemF gene. A region containing
      bent DNA (Bent 111), previously mapped to 52.6 min of the E. coli chromosome, was
      discovered in the 5' region of orf1. Two potential integration host factor
      binding sites were found, one close to each transcription start site. An open
      reading frame (orf3) transcribed in a direction opposite that of the hemF gene
      was found downstream of the hemF gene. It encodes a protein of 40.2 kDa that
      showed significant homology to proteins of the XylS/AraC family of
      transcriptional regulators.

PMID- 8300523
TI  - Role of the D-alanyl carrier protein in the biosynthesis of D-alanyl-lipoteichoic
      acid.
AB  - D-Alanyl-lipoteichoic acid (D-alanyl-LTA) is a widespread macroamphiphile which
      plays a vital role in the growth and development of gram-positive organisms. The
      biosynthesis of this polymer requires the enzymic activation of D-alanine for its
      transfer to the membrane-associated LTA (mLTA). A small, heat-stable, and acidic
      protein that is required for this transfer was purified to greater than 98%
      homogeneity from Lactobacillus casei ATCC 7469. This protein, previously named
      the D-alanine-membrane acceptor ligase (V. M. Reusch, Jr., and F. C. Neuhaus, J.
      Biol. Chem. 246:6136-6143, 1971), functions as the D-alanyl carrier protein
      (Dcp). The amino acid composition, beta-alanine content, and N-terminal sequence
      of this protein are similar to those of the acyl carrier proteins (ACPs) of fatty
      acid biosynthesis. The isolation of Dcp and its derivative, D-alanyl
      approximately Dcp, has allowed the characterization of two novel reactions in the
      pathway for D-alanyl-mLTA biosynthesis: (i) the ligation of Dcp with D-alanine
      and (ii) the transfer of D-alanine from D-alanyl approximately Dcp to a membrane
      acceptor. It has not been established whether the membrane acceptor is mLTA or
      another intermediate in the pathway for D-alanyl-mLTA biosynthesis. Since the D
      alanine-activating enzyme (EC 6.1.1.13) catalyzes the ligation reaction, this
      enzyme functions as the D-alanine-Dcp ligase (Dcl). Dcl also ligated the ACPs
      from Escherichia coli, Vibrio harveyi, and Saccharopolyspora erythraea with D
      alanine. In contrast to the relaxed specificity of Dcl in the ligation reaction,
      the transfer of D-alanine to the membrane acceptor was highly specific for Dcp
      and did not occur with other ACPs. This transfer was observed by using only D
      [14C]alanyl approximately Dcp and purified L. casei membranes. Thus, D-alanyl
      approximately Dcp is an essential intermediate in the transfer of D-alanine from
      Dcl to the membrane acceptor. The formation of D-alanine esters of mLTA provides
      a mechanism for modulating the net anionic charge in the cell wall.

PMID- 8300524
TI  - Involvement of phospholipid end groups of group C Neisseria meningitidis and
      Haemophilus influenzae type b polysaccharides in association with isolated outer
      membranes and in immunoassays.
AB  - There are several bacterial polysaccharides (PSs) which contain a terminal lipid
      moiety. It has been postulated that these terminal lipid moieties anchor the PSs
      to the outer membrane of the bacteria. Our studies have shown that incubation of
      native PS from group C Neisseria meningitidis or Haemophilus influenzae type b
      with isolated outer membrane vesicles results in association of a portion of the
      PS with the vesicles. Removal of the terminal lipid from the PS by treatment with
      phospholipase A2 or phospholipase D eliminates this association. In other
      studies, it was shown that delipidated PSs are not suitable as solid-phase
      antigens in a currently used enzyme-linked immunosorbent assay (ELISA).
      Measurement of antibody units in the reference sera by using delipidated PSs as
      antigens in an ELISA yielded negligible absorbance compared with native PSs when
      methylated human serum albumin was used to coat the PSs to the plate.
      Nevertheless, phospholipase A2 and phospholipase D treatment did not noticeably
      affect antigenic epitopes, since soluble group C PS without the terminal lipid
      bound antibody as effectively as the native PS did, as measured by a competitive
      inhibition assay. Both hydrophobic and electrostatic interactions are important
      for the binding of group C N. meningitidis PS to the ELISA plate, while charge
      interactions seem to be sufficient for binding the more negatively charged H.
      influenzae type b PS.

PMID- 8300525
TI  - Isolation and phenotypic characterization of Myxococcus xanthus mutants which are
      defective in sensing negative stimuli.
AB  - Myxococcus xanthus is a gram-negative gliding bacterium that exhibits a complex
      life cycle. Exposure of M. xanthus to chemicals like dimethyl sulfoxide (DMSO) at
      nondeleterious concentrations or the depletion of nutrients caused several
      negative responses by the cells. DMSO (> 0.1 M) or nutrient depletion triggered a
      repellent response: cell swarming was inhibited and FrzCD (a methyl-accepting
      chemotaxis protein) was demethylated; higher concentrations of DMSO (> 0.3 M) or
      prolonged starvation induced an additional response which involved cellular
      morphogenesis: DMSO caused cells to convert from rod-shaped vegetative cells to
      spherical, environmentally resistant "DMSO spores," and starvation induced
      myxospore formation in the fruiting bodies. In order to investigate the nature of
      these responses, we isolated a number of mutants defective in negative chemotaxis
      and/or sporulation. Characterization of these mutants indicated that negative
      chemotaxis plays an important role in colony swarming and in developmental
      aggregation. In addition, the results revealed some of the major
      interrelationships between the signal transduction pathways which respond to
      negative stimuli: (i) DMSO exposure and starvation were initially sensed by
      different systems, the neg system for DMSO and the stv system for starvation;
      (ii) the repellent response signals triggered by DMSO or starvation were then
      relayed by the frz signal transduction system; mutants defective in these
      responses showed altered FrzCD methylation patterns; and (iii) the morphogenesis
      signals in response to DMSO or starvation utilize a group of genes involved in
      sporulation (spo).

PMID- 8300526
TI  - Electric fields induce curved growth of Enterobacter cloacae, Escherichia coli,
      and Bacillus subtilis cells: implications for mechanisms of galvanotropism and
      bacterial growth.
AB  - Directional growth in response to electric fields (galvanotropism) is known for
      eukaryotic cells as diverse as fibroblasts, neurons, algae, and fungal hyphae.
      The mechanism is not understood, but all proposals invoke actin either directly
      or indirectly. We applied electric fields to bacteria (which are inherently free
      of actin) to determine whether actin was essential for galvanotropism. Field
      treated (but not control) Enterobacter cloacae and Escherichia coli cells curved
      rapidly toward the anode. The response was both field strength and pH dependent.
      The direction of curvature was reversed upon reversal of field polarity. The
      directional growth was not due to passive bending of the cells or to field
      induced gradients of tropic substances in the medium. Field-treated Bacillus
      subtilis cells also curved, but the threshold was much higher than for E. cloacae
      or E. coli. Since the curved morphology must reflect spatial differences in the
      rates of cell wall synthesis and degradation, we looked for regions of active
      wall growth. Experiments in which the cells were decorated with latex beads
      revealed that the anode-facing ends of cells grew faster than the cathode-facing
      ends of the same cells. Inhibitors of cell wall synthesis caused spheroplasts to
      form on the convex regions of field-treated cells, suggesting that the initial
      curvature resulted from enhanced growth of cathode-facing regions. Our results
      indicate that an electric field modulates wall growth spatially and that the
      mechanism may involve differential stimulation of wall growth in both anode- and
      cathode-facing regions. Electric fields may therefore serve as valuable tools for
      studies of bacterial wall growth. Use of specific E. coli mutants may allow
      dissection of the galvanotropic mechanism at the molecular level.

PMID- 8300527
TI  - Inhibition of erythromycin synthesis by disruption of malonyl-coenzyme A
      decarboxylase gene eryM in Saccharopolyspora erythraea.
AB  - Malonyl-coenzyme A (malonyl-CoA) decarboxylase is widely distributed in
      prokaryotes and eukaryotes. However, the biological function of this enzyme has
      not been established in any organism. To elucidate the structure and function of
      this enzyme, the malonyl-CoA decarboxylase gene from Saccharopolyspora erythraea
      (formerly Streptomyces erythreaus) was cloned and sequenced. This gene would
      encode a polypeptide of 417 amino acids. The deduced amino acid sequence matched
      the experimentally determined amino acid sequences of 25 N-terminal residues each
      of the enzyme and of an internal peptide obtained by proteolysis of the purified
      enzyme. This decarboxylase showed homology with aminoglycoside N6'
      acetyltransferases of Pseudomonas aeruginosa, Serratia marcescens, and Klebsiella
      pneumoniae. Northern (RNA) blot analysis revealed a single transcript. The
      transcription initiation site was 220 bp upstream of the start codon. When
      expressed in Escherichia coli, the S. erythraea malonyl-CoA decarboxylase gene
      yielded a protein that cross-reacted with antiserum prepared against S. erythraea
      malonyl-CoA decarboxylase and catalyzed decarboxylation of [3-14C]malonyl-CoA to
      acetyl-CoA and 14CO2. The S. erythraea malonyl-CoA decarboxylase gene was
      disrupted by homologous recombination using an integrating vector pWHM3. The gene
      disrupted transformant did not produce immunologically cross-reacting 45-kDa
      decarboxylase, lacked malonyl-CoA decarboxylase activity, and could not produce
      erythromycin. Exogenous propionate restored the ability to produce erythromycin.
      These results strongly suggest that the decarboxylase provides propionyl-CoA for
      erythromycin synthesis probably via decarboxylation of methylmalonyl-CoA derived
      from succinyl-CoA, and therefore the malonyl-CoA decarboxylase gene is designated
      eryM. The gene disrupted mutants also did not produce pigments.

PMID- 8300528
TI  - Phylogeny of Bacteroides, Prevotella, and Porphyromonas spp. and related
      bacteria.
AB  - The phylogenetic structure of the bacteroides subgroup of the cytophaga
      flavobacter-bacteroides (CFB) phylum was examined by 16S rRNA sequence
      comparative analysis. Approximately 95% of the 16S rRNA sequence was determined
      for 36 representative strains of species of Prevotella, Bacteroides, and
      Porphyromonas and related species by a modified Sanger sequencing method. A
      phylogenetic tree was constructed from a corrected distance matrix by the
      neighbor-joining method, and the reliability of tree branching was established by
      bootstrap analysis. The bacteroides subgroup was divided primarily into three
      major phylogenetic clusters which contained most of the species examined. The
      first cluster, termed the prevotella cluster, was composed of 16 species of
      Prevotella, including P. melaninogenica, P. intermedia, P. nigrescens, and the
      ruminal species P. ruminicola. Two oral species, P. zoogleoformans and P.
      heparinolytica, which had been recently placed in the genus Prevotella, did not
      fall within the prevotella cluster. These two species and six species of
      Bacteroides, including the type species B. fragilis, formed the second cluster,
      termed the bacteroides cluster. The third cluster, termed the porphyromonas
      cluster, was divided into two subclusters. The first contained Porphyromonas
      gingivalis, P. endodontalis, P. asaccharolytica, P. circumdentaria, P. salivosa,
      [Bacteroides] levii (the brackets around genus are used to indicate that the
      species does not belong to the genus by the sensu stricto definition), and
      [Bacteroides] macacae, and the second subcluster contained [Bacteroides]
      forsythus and [Bacteroides] distasonis. [Bacteroides] splanchnicus fell just
      outside the three major clusters but still belonged within the bacteroides
      subgroup. With few exceptions, the 16 S rRNA data were in overall agreement with
      previously proposed reclassifications of species of Bacteroides, Prevotella, and
      Porphyromonas. Suggestions are made to accommodate those species which do not fit
      previous reclassification schemes.

PMID- 8300529
TI  - Induced chromosome rearrangements and morphologic variation in Candida albicans.
AB  - We have isolated a mutant of Candida albicans that switches between colony
      morphologies at high frequencies in a strain with several genetic markers. This
      strain, 1183, has an altered karyotype with two extra chromosomes. The 1183
      karyotype is unstable upon passage. Using DNA transformation with the URA3 gene
      flanked by sequences from the C. albicans repeat sequence 27A, we have marked
      individual chromosomes of 1183 and 1161, a related smooth, stable strain. Many
      transformants contained one or more extra chromosomes, ranging in size from 150
      kb to 2.1 Mb. Most were less than 800 kb and appeared to be fragments of a single
      chromosome. All fragments tested derive from one of the two smallest chromosomes.
      Six of 13 fragments contained the URA3 gene. In some cases, URA3 was located at
      the end of a fragment with adjacent telomere repeats. The integrated copy of URA3
      was unstable in some 1183 transformants. Our results suggest that 1183 has a
      mutation affecting genomic stability. A connection between karyotypic changes and
      morphologic variation has been suggested from studies of several C. albicans
      strains; however, we find that gross karyotypic and morphological changes are
      separable processes.

PMID- 8300531
TI  - Molecular characterization of the P1-like adhesin gene from Mycoplasma pirum.
AB  - A DNA fragment has been isolated from the genome of Mycoplasma pirum by use of a
      genetic probe derived from the conserved region within the genes for the major
      adhesins of Mycoplasma genitalium and Mycoplasma pneumoniae. A gene encoding an
      adhesin-like polypeptide was localized, and sequence analysis indicated a G + C
      content of only 28%, with A- and T-rich codons being preferentially used. A total
      of 91% of positions 3 were either A or T. The deduced polypeptide is 1,144 amino
      acids long (126 kDa) and shows 26% identity with the adhesins of M. genitalium
      and M. pneumoniae. Other features in common with these two membrane proteins
      include a similar hydropathic profile and a proline-rich C terminus. Antibodies
      were prepared by using as an immunogen a peptide derived from the C terminus of
      the M. pirum adhesin-like polypeptide and were found to recognize on immunoblots
      a 126-kDa polypeptide from an M. pirum cellular extract. The characterization of
      the adhesin-like gene is a first step toward a better understanding of the
      mechanisms allowing this human mycoplasma to attach to host cells.

PMID- 8300530
TI  - DnaK mutants defective in ATPase activity are defective in negative regulation of
      the heat shock response: expression of mutant DnaK proteins results in
      filamentation.
AB  - Site-directed mutagenesis has previously been used to construct Escherichia coli
      dnaK mutants encoding proteins that are altered at the site of in vitro
      phosphorylation (J. S. McCarty and G. C. Walker, Proc. Natl. Acad. Sci. USA
      88:9513-9517, 1991). These mutants are unable to autophosphorylate and are
      severely defective in ATP hydrolysis. These mutant dnaK genes were placed under
      the control of the lac promoter and were found not to complement the deficiencies
      of a delta dnaK mutant in negative regulation of the heat shock response. A
      decrease in the expression of DnaK and DnaJ below their normal levels at 30
      degrees C was found to result in increased expression of GroEL. The implications
      of these results for DnaK's role in the negative regulation of the heat shock
      response are discussed. Evidence is also presented indicating the existence of a
      70-kDa protein present in a delta dnaK52 mutant that cross-reacts with antibodies
      raised against DnaK. Derivatives of the dnaK+ E. coli strain MC4100 expressing
      the mutant DnaK proteins filamented severely at temperatures equal to or greater
      than 34 degrees C. In the dnaK+ E. coli strain W3110, expression of these mutant
      proteins caused extreme filamentation even at 30 degrees C. Together with other
      observations, these results suggest that DnaK may play a direct role in the
      septation pathway, perhaps via an interaction with FtsZ. Although delta dnaK52
      derivatives of strain MC4100 filament extensively, a level of underexpression of
      DnaK and DnaJ that results in increased expression of the other heat shock
      proteins did not result in filamentation. The delta dnaK52 allele could be
      transduced successfully, at temperatures of up to 45 degrees C, into strains
      carrying a plasmid expressing dnaK+ dnaJ+, although the yield of transductants
      decreased above 37 degrees C. In contrast, with a strain that did not carry a
      plasmid expressing dnaK+ dnaJ+, the yield of delta dnaK52 transductants decreased
      extremely sharply between 39 and 40 degrees C, suggesting that DnaK and DnaJ play
      one or more roles critical for growth at temperatures of 40 degrees C or greater.

PMID- 8300532
TI  - Degradation of fluorene by Brevibacterium sp. strain DPO 1361: a novel C-C bond
      cleavage mechanism via 1,10-dihydro-1,10-dihydroxyfluoren-9-one.
AB  - Angular dioxygenation has been established as the crucial step in dibenzofuran
      degradation by Brevibacterium sp. strain DPO 1361 (V. Strubel, K. H. Engesser, P.
      Fischer, and H.-J. Knackmuss, J. Bacteriol. 173:1932-1937, 1991). The same strain
      utilizes biphenyl and fluorene as sole sources of carbon and energy. The fluorene
      degradation sequence is proposed to be initiated by oxidation of the fluorene
      methylene group to 9-fluorenol. Cells grown on fluorene exhibit pronounced 9
      fluorenol dehydrogenase activity. Angular dioxygenation of the 9-fluorenone thus
      formed yields 1,10-dihydro-1,10-dihydroxyfluoren-9-one (DDF). A mechanistic model
      is presented for the subsequent C-C bond cleavage by an NAD(+)-dependent DDF
      dehydrogenase, acting on the angular dihydrodiol. This enzyme was purified and
      characterized as a tetramer of four identical 40-kDa subunits. The following Km
      values were determined: 13 microM for DDF and 65 microM for 2,3-dihydro-2,3
      dihydroxybiphenyl. The enzyme also catalyzes the production of 3-(2'
      carboxyphenyl)catechol, which was isolated, and structurally characterized, in
      the form of the corresponding lactone, 4-hydroxydibenzo-(b,d)-pyran-6-one.
      Stoichiometry analysis unequivocally demonstrates that angular dioxygenation
      constitutes the principal pathway in Brevibacterium sp. strain DPO 1361.

PMID- 8300533
TI  - Identification of genes affecting production of the adhesive holdfast of a marine
      caulobacter.
AB  - Caulobacters are stalked bacteria that produce a structure termed a holdfast
      which enables firm attachment to surfaces. Tn5 insertion mutagenesis was used to
      identify genes affecting holdfast production or function in the marine strain
      MCS6. Twelve thousand Tn5 insertion mutants were screened for adhesion defects by
      an assay involving the attachment of cells to polystyrene microtiter dish wells.
      Among adhesion-defective mutants, those with multiple polar (pleiotropic) defects
      were excluded and the remainder were examined for the presence of holdfast. Forty
      one mutants that produced no detectable holdfast or a significantly reduced
      amount were found. Southern blot and pulsed-field gel electrophoresis analyses
      indicated that 11 unique Tn5 insertions were clustered in three regions of the
      genome. In addition, 71 mutants that adhered poorly or not at all to polystyrene,
      yet still produced a holdfast, were found. Southern blot and pulsed-field gel
      electrophoresis analyses of 15 of these mutants showed eight unique Tn5 insertion
      sites clustered in two additional regions of the genome. An assay involving
      attachment to glass treated with siloxane chemicals (producing surfaces with
      varying degrees of hydrophobicity or hydrophilicity) was used to attempt
      characterization of this phenotype. Unexpectedly, no simple pattern of
      differences in binding between the mutants and wild-type caulobacters was found.
      In particular, no reduction in the ability of the mutants to bind to hydrophobic
      surfaces was noted. Complementation with cosmid clones was successful in nearly
      all cases and confirmed the designation of five genomic regions of holdfast
      related genes. No detectable cross-hybridization was observed with several
      holdfast-related gene regions from a freshwater caulobacter, providing further
      evidence that the marine and freshwater caulobacters are genetically distinct.

PMID- 8300534
TI  - holE, the gene coding for the theta subunit of DNA polymerase III of Escherichia
      coli: characterization of a holE mutant and comparison with a dnaQ (epsilon
      subunit) mutant.
AB  - DNA polymerase III holoenzyme is a multiprotein complex responsible for the bulk
      of chromosomal replication in Escherichia coli and Salmonella typhimurium. The
      catalytic core of the holoenzyme is an alpha epsilon theta heterotrimer that
      incorporates both a polymerase subunit (alpha; dnaE) and a proofreading subunit
      (epsilon; dnaQ). The role of theta is unknown. Here, we describe a null mutation
      of holE, the gene for theta. A strain carrying this mutation was fully viable and
      displayed no mutant phenotype. In contrast, a dnaQ null mutant exhibited poor
      growth, chronic SOS induction, and an elevated spontaneous mutation rate, like
      dnaQ null mutants of S. typhimurium described previously. The poor growth was
      suppressible by a mutation affecting alpha which was identical to a suppressor
      mutation identified in S. typhimurium. A double mutant null for both holE and
      dnaQ was indistinguishable from the dnaQ single mutant. These results show that
      the theta subunit is dispensable in both dnaQ+ and mutant dnaQ backgrounds, and
      that the phenotype of epsilon mutants cannot be explained on the basis of
      interference with theta function.

PMID- 8300535
TI  - Membrane topology and mutational analysis of the TolQ protein of Escherichia coli
      required for the uptake of macromolecules and cell envelope integrity.
AB  - TolQ is a 230-amino-acid protein required to maintain the integrity of the
      bacterial envelope and to facilitate the import of both filamentous bacteriophage
      and group A colicins. Cellular fractionation experiments showed TolQ to be
      localized to the cytoplasmic membrane. Bacteria expressing a series of TolQ-beta
      galactosidase and TolQ-alkaline phosphatase fusion proteins were analyzed for the
      appropriate enzyme activity, membrane location, and sensitivity to exogenously
      added protease. The results are consistent with TolQ being an integral
      cytoplasmic membrane protein with three membrane-spanning regions. The amino
      terminal 19 residues as well as a small loop in the 155 to 170 residue region
      appear exposed in the periplasm, while the carboxy terminus and a large loop
      after the first transmembrane region are cytoplasmic. Amino-terminal sequence
      analysis of TolQ purified from the membrane revealed the presence of the
      initiating formyl methionine group, suggesting a rapid translocation of the amino
      terminal region across the cytoplasmic membrane. Analysis of various tolQ mutant
      strains suggests that the third transmembrane region as well as parts of the
      large cytoplasmic loop are necessary for activity.

PMID- 8300536
TI  - The Escherichia coli gapA gene is transcribed by the vegetative RNA polymerase
      holoenzyme E sigma 70 and by the heat shock RNA polymerase E sigma 32.
AB  - Escherichia coli D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is produced
      by the gapA gene and is structurally related to eukaryotic GAPDHs. These facts
      led to the proposal that the gapA gene originated by a horizontal transfer of
      genetic information. The yields and start sites of gapA mRNAs produced in various
      fermentation conditions and genetic contexts were analyzed by primer extension.
      The transcriptional regulatory region of the gapA gene was found to contain four
      promoter sequences, three recognized by the vegetative RNA polymerase E sigma 70
      and one recognized by the heat shock RNA polymerase E sigma 32. Transcription of
      gapA by E sigma 32 is activated in the logarithmic phase under conditions of
      starvation and of heat shock. Using a GAPDH- strain, we found that GAPDH
      production has a positive effect on cell growth at 43 degrees C. Thus, E. coli
      GAPDH displays some features of heat shock proteins. One of the gapA promoter
      sequences transcribed by E sigma 70 is subject to catabolic repression. Another
      one has growth phase-dependent efficiency. This complex area of differentially
      regulated promoters allows the production of large amounts of gapA transcripts in
      a wide variety of environmental conditions. On the basis of these data, the
      present view of E sigma 32 RNA polymerase function has to be enlarged, and the
      various hypotheses on E. coli gapA gene origin have to be reexamined.

PMID- 8300537
TI  - The mannitol repressor (MtlR) of Escherichia coli.
AB  - The mannitol operon of Escherichia coli, encoding the mannitol-specific enzyme II
      of the phosphotransferase system (Mt1A) and mannitol phosphate dehydrogenase
      (Mt1D), is here shown to contain a single additional downstream open reading
      frame which encodes the mannitol repressor (Mt1R). Mt1R contains 195 amino acids
      and has a calculated molecular weight of 21,990 and a calculated pI of 4.5. It is
      homologous to the product of an open reading frame (URF2D) upstream of the E.
      coli gapB gene but represents a novel type of transcriptional regulatory protein.

PMID- 8300538
TI  - Isolation of two physiologically induced variant strains of Bacillus
      stearothermophilus NRS 2004/3a and characterization of their S-layer lattices.
AB  - During growth of Bacillus stearothermophilus NRS 2004/3a in continuous culture on
      complex medium, the chemical properties of the S-layer glycoprotein and the
      characteristic oblique lattice were maintained only if glucose was used as the
      sole carbon source. With increased aeration, amino acids were also metabolized,
      accompanied by liberation of ammonium and by changes in the S-layer protein.
      Depending on the stage of fermentation at which oxygen limitation was relieved,
      two different variants, one with a more delicate oblique S-layer lattice (variant
      3a/V1) and one with a square S-layer lattice (variant 3a/V2), were isolated.
      During the switch from the wild-type strain to a variant or from variant 3a/V2 to
      variant 3a/V1, monolayers of two types of S-layer lattices could be demonstrated
      on the surfaces of single cells. S-layer proteins from variants had different
      molecular sizes and a significantly lower carbohydrate content than S-layer
      proteins from the wild-type strain did. Although the S-layer lattices from the
      wild-type and variant strains showed quite different protein mass distributions
      in two- and three-dimensional reconstructions, neither the amino acid composition
      nor the pore size, as determined by permeability studies, was significantly
      changed. Peptide mapping and N-terminal sequencing results strongly indicated
      that the three S-layer proteins are encoded by different genes and are not
      derived from a universal precursor form.

PMID- 8300539
TI  - Molecular characterization of enterobacterial pldA genes encoding outer membrane
      phospholipase A.
AB  - The pldA gene of Escherichia coli encodes an outer membrane phospholipase A. A
      strain carrying the most commonly used mutant pldA allele appeared to express a
      correctly assembled PldA protein in the outer membrane. Nucleotide sequence
      analysis revealed that the only difference between the wild type and the mutant
      is the replacement of the serine residue in position 152 by phenylalanine. Since
      mutants that lack the pldA gene were normally viable under laboratory conditions
      and had no apparent phenotype except for the lack of outer membrane phospholipase
      activity, the exact role of the enzyme remains unknown. Nevertheless, the enzyme
      seems to be important for the bacteria, since Western blotting (immunoblotting)
      and enzyme assays showed that it is widely spread among species of the family
      Enterobacteriaceae. To characterize the PldA protein further, the pldA genes of
      Salmonella typhimurium, Klebsiella pneumoniae, and Proteus vulgaris were cloned
      and sequenced. The cloned genes were expressed in E. coli, and their gene
      products were enzymatically active. Comparison of the predicted PldA primary
      structures with that of E. coli PldA revealed a high degree of homology, with 79%
      of the amino acid residues being identical in all four proteins. Implications of
      the sequence comparison for the structure and the structure-function relationship
      of PldA protein are discussed.

PMID- 8300540
TI  - Molecular characterization of an aldehyde/alcohol dehydrogenase gene from
      Clostridium acetobutylicum ATCC 824.
AB  - A gene (aad) coding for an aldehyde/alcohol dehydrogenase (AAD) was identified
      immediately upstream of the previously cloned ctfA (J. W. Cary, D. J. Petersen,
      E. T. Papoutsakis, and G. N. Bennett, Appl. Environ. Microbiol. 56:1576-1583,
      1990) of Clostridium acetobutylicum ATCC 824 and sequenced. The 2,619-bp aad
      codes for a 96,517-Da protein. Primer extension analysis identified two
      transcriptional start sites 83 and 243 bp upstream of the aad start codon. The N
      terminal section of AAD shows homology to aldehyde dehydrogenases of bacterial,
      fungal, mammalian, and plant origin, while the C-terminal section shows homology
      to alcohol dehydrogenases of bacterial (which includes three clostridial alcohol
      dehydrogenases) and yeast origin. AAD exhibits considerable amino acid homology
      (56% identity) over its entire sequence to the trifunctional protein encoded by
      adhE from Escherichia coli. Expression of aad from a plasmid in C. acetobutylicum
      showed that AAD, which appears as a approximately 96-kDa band in denaturing
      protein gels, provides elevated activities of NADH-dependent butanol
      dehydrogenase, NAD-dependent acetaldehyde dehydrogenase and butyraldehyde
      dehydrogenase, and a small increase in NADH-dependent ethanol dehydrogenase. A
      957-bp open reading frame that could potentially encode a 36,704-Da protein was
      identified upstream of aad.

PMID- 8300541
TI  - Azorhizobium caulinodans respires with at least four terminal oxidases.
AB  - In culture, Azorhizobium caulinodans used at least four terminal oxidases,
      cytochrome aa3 (cytaa3), cytd, cyto, and a second a-type cytochrome, which
      together mediated general, respiratory electron (e-) transport to O2. To
      genetically dissect physiological roles for these various terminal oxidases,
      corresponding Azorhizobium apocytochrome genes were cloned, and three cytaa3
      mutants, a cytd mutant, and a cytaa3, cytd double mutant were constructed by
      reverse genetics. These cytochrome oxidase mutants were tested for growth,
      oxidase activities, and N2 fixation properties both in culture and in symbiosis
      with the host plant Sesbania rostrata. The cytaa3 mutants grew normally, fixed N2
      normally, and remained fully able to oxidize general respiratory e- donors (NADH,
      succinate) which utilize a cytc-dependent oxidase. By difference spectroscopy, a
      second, a-type cytochrome was detected in the cytaa3 mutants. This alternative a
      type cytochrome (Amax = 610 nm) was also present in the wild type but was masked
      by bona fide cytaa3 (Amax = 605 nm). In late exponential-phase cultures, the
      cytaa3 mutants induced a new, membrane-bound, CO-binding cytc550, which also
      might serve as a cytc oxidase (a fifth terminal oxidase). The cloned Azorhizobium
      cytaa3 genes were strongly expressed during exponential growth but were
      deactivated prior to onset of stationary phase. Azorhizobium cytd mutants showed
      40% lower N2 fixation rates in culture and in planta, but aerobic growth rates
      were wild type. The cytaa3, cytd double mutant showed 70% lower N2 fixation rates
      in planta. Pleiotropic cytc mutants were isolated by screening for strains unable
      to use N,N,N',N'-tetramethyl-p-phenylenediamine as a respiratory e- donor. These
      mutants synthesized no detectable cytc, excreted coproporphyrin, grew normally in
      aerobic minimal medium, grew poorly in rich medium, and fixed N2 poorly both in
      culture and in planta. Therefore, while aerobic growth was sustained by quinol
      oxidases alone, N2 fixation required cytc oxidase activities. Assuming that the
      terminal oxidases function as do their homologs in other bacteria, Azorhizobium
      respiration simultaneously employs both quinol and cytc oxidases. Because
      Azorhizobium terminal oxidase mutants were able to reformulate their terminal
      oxidase mix and grow more or less normally in aerobic culture, these terminal
      oxidases are somewhat degenerate. Its extensive terminal oxidase repertoire might
      allow Azorhizobium spp. to flourish in wide-ranging O2 environments.

PMID- 8300542
TI  - Structure, composition, and assembly of paracrystalline phycobiliproteins in
      Synechocystis sp. strain BO 8402 and of phycobilisomes in the derivative strain
      BO 9201.
AB  - The phycobiliproteins of the unicellular cyanobacterium Synechocystis sp. strain
      BO 8402 and its derivative strain BO 9201 are compared. The biliproteins of
      strain BO 8402 are organized in paracrystalline inclusion bodies showing an
      intense autofluorescence in vivo. These protein-pigment aggregates have been
      isolated. The highly purified complexes contain phycocyanin with traces of
      phycoerythrin, corresponding linker polypeptides LR35PC and LR33PE (the latter in
      a small amount), and a unique colored polypeptide with an M(r) of 55,000,
      designated L55. Allophycocyanin and the core linker polypeptides are absent. The
      substructure of the aggregates has been studied by electron microscopy.
      Repetitive subcomplexes of hexameric stacks of biliproteins form extraordinary
      long rods associated side by side in a highly condensed arrangement. Evidence
      that the linker polypeptides LR35PC and LR33PE stabilize the biliprotein hexamers
      is presented, while the location and function of the colored linker L55 remain
      uncertain. The derivative strain BO 9201 contains established hemidiscoidal
      phycobilisomes comprising phycoerythrin, phycocyanin, and allophycocyanin as well
      as the corresponding linker polypeptides. The core-membrane linker protein (LCM),
      and two polypeptides with M(r)s of 40,000 and 45,000 which are present in small
      amounts, exhibit strong cross-reactivity in Western blot (immunoblot) analysis
      using an antibody directed against the colored LCM of a Nostoc sp. In contrast,
      strain BO 8402 exhibits no polypeptide with a significant immunological cross
      reactivity in Western blot analysis. Physiological and genetic implications of
      the unusual pigment compositions of both strains are discussed.

PMID- 8300544
TI  - Effect of pH on sulfite oxidation by Thiobacillus thiooxidans cells with
      sulfurous acid or sulfur dioxide as a possible substrate.
AB  - The oxidation of sulfite by Thiobacillus thiooxidans was studied at various pH
      values with changing concentrations of potassium sulfite. The optimal pH for
      sulfite oxidation by cells was a function of sulfite concentrations, rising with
      increasing substrate concentrations, while that by the cell extracts was
      unaffected. The sulfite oxidation by cells was inhibited at high sulfite
      concentrations, particularly at low pH values. The results from kinetic studies
      show that the fully protonated form of sulfite, sulfurous acid or sulfur dioxide,
      is the form which penetrates the cells for the oxidation.

PMID- 8300543
TI  - The spv virulence operon of Salmonella typhimurium LT2 is regulated negatively by
      the cyclic AMP (cAMP)-cAMP receptor protein system.
AB  - The cyclic AMP (cAMP) receptor protein (CRP) was found to play a role in the
      growth phase regulation of the spv operon on the high-molecular-weight virulence
      plasmid of Salmonella typhimurium LT2. By using a lacZ reporter transcriptional
      fusion to the spvB structural gene on the single-copy virulence plasmid, it was
      found that while spvB transcription was induced in stationary-phase cultures, the
      induced level of expression was lower than that reported for the spv system in
      other serovars of Salmonella. Surprisingly, inactivation of the gene encoding the
      positive activator SpvR resulted in only a threefold reduction in spvB
      transcription. In contrast, spvB transcription in stationary-phase cultures was
      enhanced by 10-fold in mutants deficient in crp-encoded CRP or cya-encoded
      adenylate cyclase. Wild-type (i.e., 10-fold-lower) levels of spvB expression were
      restored by providing active copies of crp or cya on recombinant plasmids.
      Enhanced spvB transcription was not seen in crp or cya mutants in the absence of
      a functional spvR positive regulatory gene, showing that the cAMP-CRP system
      acted on spvB expression either in conjunction with or via SpvR. A lacZ
      transcriptional fusion to spvR could not be induced in stationary-phase cultures
      in the absence of functional SpvR, regardless of the cAMP-CRP status of the
      cells. When SpvR was provided in trans, transcription of the spvR-lacZ fusion was
      induced to similar levels in stationary-phase cultures with and without cAMP-CRP.
      These data are consistent with spvR being poorly transcribed from the single-copy
      virulence plasmid in S. typhimurium LT2 and with a suppression of this defect via
      inactivation of the cAMP-CRP system. The physiological significance of cAMP-CRP
      involvement in spv expression is discussed.

PMID- 8300545
TI  - Cytoplasmic axial filaments in Escherichia coli cells: possible function in the
      mechanism of chromosome segregation and cell division.
AB  - Overproduction of CafA caused formation of chained cells and minicells. The cafA
      gene is located downstream from the mre region at 71 min on the Escherichia coli
      chromosome map and was previously called orfF. A long axial structure running
      through the chained cells, consisting of bundles of filaments assembled in a long
      hexagonal pillar several micrometers long and about 0.1 to 0.2 micron in
      diameter, was visible in both phase-contrast micrographs of the lysozyme-treated
      cells and electron micrographs of ultrathin sections. The CafA protein displays
      34% amino acid similarity with the N terminus of the Ams protein of E. coli,
      which cross-reacts with antibody to a nonmuscle myosin heavy chain.

PMID- 8300546
TI  - Analysis of the peptidoglycan of Rickettsia prowazekii.
AB  - In the present study, peptidoglycan from Rickettsia prowazekii, an obligate
      intracellular bacterium, was purified. The rickettsial peptidoglycan is like that
      of gram-negative bacteria; that is, it is sodium dodecyl sulfate insoluble,
      lysozyme sensitive, and composed of glutamic acid, alanine, and diaminopimelic
      acid in a molar ratio of 1.0:2.3:1.0. The small amount of lysine found in the
      peptidoglycan preparation suggests that a peptidoglycan-linked lipoprotein(s) may
      be present in the rickettsiae. D-Cycloserine, a D-alanine analog which inhibits
      the biosynthesis of bacterial cell walls, prevented rickettsial growth in mouse
      L929 cells at a high concentration and altered the morphology of the rickettsiae
      at a low concentration. These effects were prevented by the addition of D
      alanine. This suggests that R. prowazekii contains D-alanine in the peptidoglycan
      and has D-Ala-D-Ala ligase and alanine racemase activities.

PMID- 8300547
TI  - The importance of four histidine residues in isocitrate lyase from Escherichia
      coli.
AB  - By site-directed mutagenesis, substitutions were made for His-184 (H-184), H-197,
      H-266, and H-306 in Escherichia coli isocitrate lyase. Of these changes, only
      mutations of H-184 and H-197 appreciably reduced enzyme activity. Mutation of H
      184 to Lys, Arg, or Leu resulted in an inactive isocitrate lyase, and mutation of
      H-184 to Gln resulted in an enzyme with 0.28% activity. Nondenaturing
      polyacrylamide gel electrophoresis demonstrated that isocitrate lyase containing
      the Lys, Arg, Gln, and Leu substitutions at H-184 was assembled poorly into the
      tetrameric subunit complex. Mutation of H-197 to Lys, Arg, Leu, and Gln resulted
      in an assembled enzyme with less than 0.25% wild-type activity. Five
      substitutions for H-266 (Asp, Glu, Val, Ser, and Lys), four substitutions for H
      306 (Asp, Glu, Val, and Ser), and a variant in which both H-266 and H-306 were
      substituted for showed little or no effect on enzyme activity. All the H-197, H
      266, and H-306 mutants supported the growth of isocitrate lyase-deficient E. coli
      JE10 on acetate as the sole carbon source; however, the H-184 mutants did not.

PMID- 8300548
TI  - Identification of a hydride-Meisenheimer complex as a metabolite of 2,4,6
      trinitrotoluene by a Mycobacterium strain.
AB  - A bacterial strain, Mycobacterium sp. strain HL 4-NT-1, enriched with 4
      nitrotoluene as its sole source of nitrogen, was able to metabolize 2,4,6
      trinitrotoluene under aerobic conditions. The dark red-brown metabolite, which
      accumulated in the culture fluid, was identified as a hydride-Meisenheimer
      complex by comparison with an authentic synthetic sample.

PMID- 8300549
TI  - Expression of the Bacillus subtilis spoIVCA gene, which encodes a site-specific
      recombinase, depends on the spoIIGB product.
AB  - The Bacillus subtilis spoIVCA gene encodes a site-specific recombinase which
      creates a sigK gene by DNA rearrangement. We have determined the transcription
      initiation point of the spoIVCA gene and found that (i) the spoIVCA promoter
      contains sequences which are similar to -10 and -35 regions of promoters
      recognized by sigma E and (ii) mutation of spoIIGB, which encodes pro-sigma E,
      blocked the expression of spoIVCA.

PMID- 8300550
TI  - Extracorporeal circuit heparinization in selective low density lipoprotein
      apheresis: changes in patient hemostasis and low molecular weight heparin
      benefit.
AB  - Treatment by low density lipoprotein (LDL) apheresis using dextran sulfate
      columns (DSC) leads to hemostasis alterations with prolonged activated partial
      thromboplastin time (APTT) of more than 120 seconds. In order to explain this
      hypocoagulability, we studied hemostasis parameters both in patients and in the
      extracorporeal circulation (ECC). Hemostasis changes are first related to
      unfractionated heparin (UFH)--needed to avoid circuit coagulation--which leads to
      high residual heparinemia in the patient (more than 3 times the recommended level
      for therapeutic use). Second, the hypocoagulability is induced by a coagulation
      factor decrease (primarily factors V, VIII, and X) mainly due to an adsorption
      mechanism on dextran sulfate. Studies on samples from column inflow, outflow, and
      eluate confirm this mechanism. Low molecular weight heparin (LMWH) can be used in
      LDL apheresis on DSC without major changes in lipid removal or coagulation
      factors compared to UFH. The benefit of using LMWH is to reduce residual
      heparinemia into the therapeutic range.

PMID- 8300551
TI  - Hypercoagulable state induced by thrombocytapheresis.
AB  - The influence of the continuous-flow automated blood cell separator. Fenwal CS
      3000, on blood coagulation and the fibrinolytic system in blood donors was
      studied. Blood samples were taken from the collection line of donors undergoing
      extracorporeal circulation, before and after platelet pheresis. Of the molecular
      markers, prothrombin fragment-F1 + 2 (PF1 + 2) markedly increased from 0.8 +/-
      0.3 to 2.9 +/- 2.0 nM/ml (P < .004), thrombin antithrombin III complex (TAT) also
      markedly increased from 2.6 +/- 1.3 to 56.0 +/- 24.0 micrograms/L (P < .001),
      fibrinopeptide A (FPA) increased slightly from 0.8 +/- 0.9 to 3.8 +/- 4.2
      micrograms/L (P < .05), and alpha 2-plasmin inhibitor (alpha 2-PI) decreased
      slightly from 95 +/- 8 to 91 +/- 9% (P < .05). In one donor with the highest
      level of PF1 + 2, TAT, FPA, and plasmin inhibitor complex after platelet
      pheresis, protein C, protein S, C4b-binding protein, ATIII, plasminogen, alpha 2
      PI, and coagulation factors were decreased. In blood donors undergoing platelet
      pheresis using the continuous-flow automated blood cell separator, Fenwal CS
      3000, a hypercoagulable state was observed. Changing the materials of the plastic
      disposables to a more thromboresistant material may prevent the hypercoagulable
      state in donors induced by platelet pheresis using the blood cell separator.

PMID- 8300552
TI  - Sudden onset bilateral deafness during therapeutic leukapheresis.

PMID- 8300553
TI  - HIV--science, politics, and policy: what have we learned?

PMID- 8300555
TI  - New trends in HIV/AIDS epidemiology.
AB  - World geographic patterns of HIV infection are discussed. Various parameters such
      as age, route of transmission, exposure, culture, and geographical influences are
      addressed. Future trends for HIV infection and development of AIDS and associated
      disorders such as non-Hodgkin's lymphoma are suggested and strategies are
      suggested to reduce the impact of this epidemic.

PMID- 8300554
TI  - HIV infection at home and in the workplace.
AB  - Major questions have been raised concerning an individual's risk for contracting
      HIV infection when they come into contact with a patient who has AIDS in the home
      and/or workplace. Specific concerns are addressed and guidelines are reviewed.

PMID- 8300556
TI  - What does the future hold for patients infected with HIV?

PMID- 8300557
TI  - A Leu-Leu sequence is essential for COOH-terminal targeting signal of GLUT4
      glucose transporter in fibroblasts.
AB  - In the insulin-responsive tissues, muscle and adipose, the GLUT4 glucose
      transporter isoform accounts for most of the increase in hexose flux in response
      to hormone. In these cell types, as well as in fibroblasts transfected with cDNAs
      encoding the transporters, GLUT1 and GLUT4 are sorted to different subcellular
      locations. In the latter, GLUT1 is found primarily at the cell surface whereas
      GLUT4 localizes to the interior of the cell in a perinuclear distribution. The
      construction and analysis of chimeras of these two transporter isoforms have
      allowed identification of the COOH-terminal 30 amino acids as a critical sorting
      signal for differential localization of the transporters. In this study, we show
      that 2 residues present in the GLUT4 COOH terminus, Leu-489 and Leu-490, are
      critical for the intracellular sequestration of this isoform in NIH3T3 cells.

PMID- 8300558
TI  - Molecular cloning of the CD45-associated 30-kDa protein.
AB  - CD45, a leukocyte-specific transmembrane protein tyrosine phosphatase, mediates
      signal transduction pathways critical for immune responses. However, the
      mechanism of CD45-mediated signal transduction and the identity of CD45
      associated proteins have remained unclear. A CD45-associated 30-kDA
      phosphorylated protein (CD45-AP) was purified by virtue of its specific
      association with CD45, and its mouse cDNA was cloned by using the internal amino
      acid sequence information. In vitro translated CD45-AP bound specifically to
      CD45. CD45-AP appears to be leukocyte-specific and shares no significant homology
      with presently known sequences. The predicted sequence contains no consensus
      tyrosine phosphorylation sites or conserved sequences of GTP-binding proteins.
      CD45-AP may act as an adapter molecule for CD45-mediated signal transduction.

PMID- 8300559
TI  - Cloning and recombinant expression of a novel human low molecular weight Ca(2+)
      dependent phospholipase A2.
AB  - Extensive biochemical studies of phospholipase A2s (PLA2s) over the last two
      decades indicate that there are likely to be several distinct PLA2 genes in
      mammals. Here we report the cloning of a 1-kilobase pair cDNA encoding a novel
      human low molecular weight PLA2. The cDNA appears to encode a 118-amino acid
      mature peptide (M(r) = 13,592) preceded by a 20-residue prepeptide. The deduced
      amino acid sequence encodes a protein that lacks one of the seven disulfide
      bridges found in similar PLA2s and, therefore, represents a class of enzymes
      distinct from the mammalian group I and group II enzymes. An RNA blot hybridized
      with the cDNA exhibited a putative 1.2-kilobase pair transcript in heart and,
      less abundantly, in lung, as well as multiple putative transcripts in placenta.
      When the cDNA was expressed using an Epstein-Barr virus-based vector in human
      293s cells, PLA2 activity accumulated in the culture medium. Conditioned medium
      optimally hydrolyzed the phospholipids of [1-14C]oleate-labeled Escherichia coli
      at neutral to alkaline pH with 10 mM or greater Ca2+. In assays done with
      individual substrates, L-alpha-1-palmitoyl-2-oleoyl phosphatidylcholine was more
      efficiently hydrolyzed than L-alpha-1-palmitoyl-2-arachidonyl
      phosphatidylcholine, L-alpha-1-palmitoyl-2-arachidonyl phosphatidylethanolamine,
      or L-alpha-1-stearoyl-2-arachidonyl phosphatidylinositol.

PMID- 8300560
TI  - Control of the yeast bud-site assembly GTPase Cdc42. Catalysis of guanine
      nucleotide exchange by Cdc24 and stimulation of GTPase activity by Bem3.
AB  - Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated
      reorganizations of cortical cytoskeletal elements and requires the action of the
      Rho (Ras homologous)-type GTPase Cdc42. As a first step toward understanding how
      these cytoskeletal rearrangements are controlled, we have sought to identify
      those proteins that regulate the binding and hydrolysis of GTP by Cdc42. Here we
      report that the product of the CDC24 gene, which is required for proper bud-site
      selection and bud emergence, can stimulate the exchange of GTP for GDP on Cdc42.
      Combined with previously reported genetic data, this finding suggests that the
      processes of bud-site selection (which requires the action of a Ras-type GTPase)
      and bud-site assembly might be coordinated through an activator of a Rho-type
      GTPase. We also report the identification of a new gene, BEM3, that is a
      multicopy suppressor of the temperature-sensitive lethality caused by mutations
      in the bud emergence gene BEM2. Bem3 and Bem2 both contain a Rho GTPase
      activating protein homology domain, but only Bem3 is able to stimulate the
      hydrolysis of GTP on Cdc42. These studies demonstrate that Cdc24 and Bem3 have
      GDP-release factor activity and GTPase-activating protein activity, respectively,
      toward the essential bud-site assembly GTPase Cdc42.

PMID- 8300561
TI  - A threonine residue in the seventh transmembrane domain of the human A1 adenosine
      receptor mediates specific agonist binding.
AB  - The A1 adenosine receptor is a member of the seven-transmembrane G protein
      coupled, receptor superfamily. This receptor binds the purine nucleoside
      adenosine with high affinity and inhibits the activity of adenylate cyclase. We
      have used site-directed mutagenesis and functional expression studies to examine
      the role of the threonine residue, located at position 277 in transmembrane
      domain VII of the human A1 receptor. Mutation of Thr-277 to either serine or
      alanine resulted in the expression of receptors that had essentially no change in
      binding affinity for the A1 selective antagonist 8-cyclo-pentyl-1,3
      dipropylxanthine. Mutation of Thr-277 to serine resulted in modest (4.4-8.6-fold)
      but significant increases in the observed Ki values for three adenosine agonists,
      namely N-(1-methyl-2-phenethyl)adenosine (R-PIA or S-PIA) and 1-(6-amino-9H-purin
      9-yl)-1-deoxy-N-ethyl-beta-L- ribofuranuronamide) (NECA). However, mutation of
      Thr-277 to alanine resulted in no significant changes in the Ki for R-PIA or S
      PIA but did result in a highly significant 437-fold increase in the Ki for NECA.
      This demonstrates that the hydroxyl moiety of Thr-277 mediates agonist but not
      antagonist binding and, more specifically, that this residue forms a probable
      molecular contact site with the 5' substitution found in NECA.

PMID- 8300562
TI  - The tyrosine B10 hydroxyl is crucial for oxygen avidity of Ascaris hemoglobin.
AB  - The parasitic nematode Ascaris suum has a gene encoding a two-domain hemoglobin
      with remarkable oxygen avidity. The strong interaction with oxygen is a
      consequence of a particularly slow oxygen off-rate. The single polypeptide chain
      consists of two domains, each of which can be expressed separately in Escherichia
      coli as a globin-like protein exhibiting oxygen binding characteristics
      comparable with the native molecule. Site-directed mutagenesis was performed on
      the gene segment encoding domain one. The E7 position, involved in forming a
      hydrogen bond with the liganded oxygen in vertebrate globins, is a glutamine in
      both Ascaris domains. Conversion of this residue to leucine or alanine produced a
      hemoglobin variant with an oxygen off-rate 5- or 60-fold faster than that of
      unaltered domain one. Replacement of the tyrosine B10 with either phenylalanine
      or leucine (as found in vertebrate globins) yielded hemoglobin mutants with
      oxygen off-rates 280- or 570-fold faster, approaching rates found with vertebrate
      myoglobins. The data suggest that the distal glutamine hydrogen bonds with the
      liganded oxygen and that the tyrosine B10 hydroxyl contributes an additional
      hydrogen bond that appears substantially responsible for the extreme oxygen
      avidity of Ascaris hemoglobin.

PMID- 8300563
TI  - Delta 3,5, delta 2,4-dienoyl-CoA isomerase from rat liver mitochondria.
      Purification and characterization of a new enzyme involved in the beta-oxidation
      of unsaturated fatty acids.
AB  - Mitochondrial delta 3,5, delta 2,4-dienoyl-CoA isomerase, which catalyzes the
      conversion of 3,5-octadienoyl-CoA to 2,4-octadienoyl-CoA, was purified from rat
      liver 370-fold at almost 30% yield by a six-step purification procedure. The
      final preparation appeared to be homogeneous as judged by gel electrophoresis.
      The molecular weights of the native enzyme and its subunit(s) were estimated to
      be 126,000 and 32,000, respectively. The purification of delta 3,5, delta 2,4
      dienoyl-CoA isomerase completes the characterization of the enzymes functioning
      in the NADPH-dependent pathway for the beta-oxidation of unsaturated fatty acids
      with double bonds extending from odd-numbered carbon atoms. This novel pathway
      may not be operative in peroxisomes because delta 3,5, delta 2,4-dienoyl-CoA
      isomerase was only detected in mitochondria. Substrates of this pathway are 2,5
      dienoyl-CoAs formed from 5-enoyl-CoAs by acyl-CoA dehydrogenase. Two sequential
      isomerization reactions catalyzed by delta 3, delta 2-enoyl-CoAs isomerase and
      delta 3,5, delta 2,4-dienoyl-CoA isomerase, respectively, convert 2,5-dienoyl
      CoAs to 2,4-dienoyl-CoAs, which are reduced by NADPH-dependent 2,4-dienoyl-CoA
      reductase (EC 1.3.1.34) before reentering the beta-oxidation spiral.

PMID- 8300564
TI  - Activation of a voltage-dependent chloride current in human neutrophils by
      phorbol 12-myristate 13-acetate and formyl-methionyl-leucyl-phenylalanine. The
      role of protein kinase C.
AB  - Calcium-activated, voltage-independent Cl- currents have been demonstrated in
      human neutrophils (Krause, K.-H., and Welsh, M.J. (1990) J. Clin. Invest. 85, 491
      498). The activation is mediated by calcium/calmodulin-dependent protein kinase
      and not by protein kinase C (PKC) (Schumann, M., Gardner, A.P., and Raffin, T.A.
      (1993) J. Biol. Chem. 268, 2134-2140). It is not known whether there are Ca(2+)
      independent, voltage-dependent Cl- currents in these cells. Using K(+)-free
      solutions and patch-clamp recordings from human neutrophils, we separated the
      whole cell Cl- current. Base-line Cl- currents of unstimulated cells were small
      and displayed time and voltage independence; some showed voltage dependence. With
      a Ca(2+)-free pipette solution, bath-administered 1 microM phorbol 12-myristate
      13-acetate (PMA) or 0.1 microM N-formyl-methionyl-leucyl-phenylalanine (fMLP) for
      10 s induced augmented Cl- currents with voltage- and time-dependent outwardly
      rectifying properties. The threshold voltage of tail Cl- current activation was 
      69 mV. With a pipette solution containing 0.1 mM Ca2+, bath-administered 0.1
      microM fMLP, 1 microM PMA, or 1 microM Ca2+ ionophore A23187 for 30 s induced
      augmented Cl- currents with voltage-independent properties. With intracellular
      application of 5 microM PKC inhibitor PKC(19-36), voltage-dependent Cl- currents
      were no longer activated by PMA or fMLP. Similar application of 5 microM PKC
      noninhibitory analog [Glu27]PKC(19-36) did not block PMA (or fMLP)-induced Cl-
      currents. These results indicate that, in addition to Ca(2+)-activated Cl-
      currents, human neutrophils have voltage-dependent Cl- currents which are
      regulated by PKC.

PMID- 8300565
TI  - Exposure of phosphatidylserine in the outer leaflet of human red blood cells.
      Relationship to cell density, cell age, and clearance by mononuclear cells.
AB  - Human red blood cells (RBC) were separated by density on self-forming Percoll
      gradients into five distinct populations. The transbilayer movement and
      equilibrium distribution of 1-oleoyl-2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-
      yl)aminocaproyl)phosphatidylserine (NBD-PS) was slower in dense cells and
      equilibrated in the inner leaflet of these cells to a lesser degree than in light
      cells. Conversely, the outward movement of the lipid was slower in light cells.
      Assessment of endogenous PS in the cells' outer leaflet by the prothrombinase
      activity of externalized PS revealed an increase in its presence at the cell
      surface with increasing cell density. The presence of PS on the cell surface
      directly correlated with the propensity of the RBC to bound by autologous
      monocytes. To determine whether increased cell density is associated with
      increased cell age, the in vivo clearance of density-separated murine RBC was
      monitored in syngeneic mice. The T1/2 of circulation of light cells was about
      twice that of dense cells. The majority of the cleared cells localized in the
      spleen. Studies carried out in antibody-deficient SCID mice indicated that RBC
      were cleared via a mechanism that was independent of antibody. These data suggest
      that cell age is related to cell density and that cells of increasing age and
      density display higher amounts of PS in their outer leaflet.

PMID- 8300566
TI  - Identification of oxidized histidine generated at the active site of Cu,Zn
      superoxide dismutase exposed to H2O2. Selective generation of 2-oxo-histidine at
      the histidine 118.
AB  - Inactivation of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) by its own reaction
      product H2O2 is a well-known phenomenon. Generation of the hydroxyl radical has
      been a matter of great concern, and the target molecule has been regarded as its
      own active site histidine residues, whose oxidized forms have not yet been
      identified (Hodgson, E.K., and Fridovich, I. (1975) Biochemistry 14, 5294-5299).
      Here we report on the identification of oxidized histidines generated at the
      active site of Cu,Zn-SOD by reaction with H2O2. When bovine erythrocyte Cu,Zn-SOD
      (0.5 mg/ml) was treated with 5 mM H2O2 in 50 mM sodium phosphate buffer (pH 7.2),
      histidine was significantly lost; however, except for a significant increase in
      aspartate and glutamate, nothing new appeared in the amino acid analysis of
      oxidized Cu,Zn-SOD. On the other hand, the hydrolysates of oxidized Cu,Zn-SOD
      involved an unknown product that was detectable by reverse-phase high performance
      liquid chromatography with electrochemical detection. The product was found to be
      identical to 2-oxo-histidine that had been discovered as the major oxidation
      product of histidine and its peptides treated with a copper/ascorbate-free
      radical generating system. The main product present in the hydrolysate of H2O2
      treated Cu,Zn-SOD was 2-oxo-histidine. Approximately 0.66 mol/mol subunit was
      formed when Cu,Zn-SOD was treated with 5 mM H2O2 for 30 min. Both metal chelators
      and the hydroxyl radical scavengers only slightly inhibited the 2-oxo-histidine
      formation (10-39%), suggesting that the active species were produced mainly
      inside the ligands of the Cu2+ in the enzyme. Trypsin digestion of H2O2-treated
      Cu,Zn-SOD showed selective reactions at the sequences of Gly24-Lys67 and Thr114
      Arg126, in that histidine residues locate at the active center. Two new products
      derived from those peptides appeared in the tryptic map. Amino acid analysis of
      both products demonstrated the loss of only histidine. One of them derived from
      Thr114-Arg126 contained an equimolar amount of 2-oxo-histidine, indicating that
      His-118 was converted selectively to 2-oxo-histidine; however, another product
      derived from Gly24-Lys67 contained only 0.085 mol of 2-oxo-histidine/mol of
      peptide, suggesting that the product is a mixture consisting of unidentified
      forms of oxidized histidine. Taken together, the present study provided direct
      evidence that 2-oxo-histidine was generated in the Cu,Zn-SOD exposed to H2O2 and
      that its generation was selective at histidine 118 of the active site of the
      enzyme.

PMID- 8300567
TI  - Characterization of plasminogen activation by glycosylphosphatidylinositol
      anchored urokinase.
AB  - The characteristics of plasminogen activation by glycosylphosphatidylinositol
      (GPI)-anchored urokinase were evaluated and compared with those reported
      previously for receptor-bound urokinase. When expressed in cultured bovine aortic
      endothelial cells, GPI anchoring of single-chain urokinase plasminogen activator
      (scu-PA) potentiated plasmin generation as compared with GPI-anchored scu-PA that
      had been released into solution from the cell surface by enzymatic cleavage of
      the GPI anchor ("released" scu-PA). The potentiation of plasmin generation by GPI
      anchored scu-PA was inhibited in a dose-dependent manner by 6-aminohexanoic acid,
      a lysine analog, suggesting that the augmentation of plasmin generation by GPI
      anchored scu-PA was dependent on simultaneous binding of plasminogen to the cell
      surface. GPI-anchored two-chain urokinase (tcu)-PA cleaved a peptide substrate at
      a rate equivalent to that of released urokinase. However, at a plasminogen
      concentration of 0.5 microM, GPI-anchored tcu-PA activated plasminogen less
      rapidly than did released urokinase. Modeling of kinetics of individual reactions
      revealed that cell-associated plasminogen activation by GPI-anchored tcu-PA was
      characterized by a Km of approximately 0.15 microM. This value of Km was 70-fold
      below that for activation of solution plasminogen by GPI-anchored urokinase.
      There was a concomitant decrease in Vmax for plasminogen activation by anchored
      tcu-PA. These alterations in kinetic parameters are similar to those reported
      previously for the activation of plasminogen by receptor-bound tcu-PA. In
      addition, GPI-anchored tcu-PA exhibited a modest resistance to plasminogen
      activator inhibitor 1 inactivation. The enzymatic characteristics of GPI-anchored
      urokinase reported here resemble closely those reported previously for receptor
      bound urokinase. These data suggest that the urokinase receptor may regulate
      plasmin generation through a relatively nonspecific localization of urokinase to
      the cell surface rather than through any intrinsic property of the urokinase
      receptor.

PMID- 8300568
TI  - Modeling the sequence of electron transfer reactions in the single turnover of
      reduced, mammalian cytochrome c oxidase with oxygen.
AB  - Single-turnover studies of the reaction of reduced cytochrome oxidase with oxygen
      has led to a mechanistic model that specifies a linear sequence of electron
      transfer from cytochrome c to O2 via the four redox active metals of
      mitochondrial cytochrome oxidase. Fully reduced oxidase initially forms a
      dioxygen adduct within which two electrons are transferred at a rate of 6 x 10(4)
      s-1 to form a peroxy adduct. This two-electron step results in single-electron
      oxidation of cytochrome alpha 3 and cytochrome alpha. Cytochrome alpha is then re
      reduced by CuA in an intramolecular reaction. Subsequent reoxidation of
      cytochrome alpha occurs at a rate nearly 100-fold slower than its initial
      oxidation. Oxidation of CuB in this sequence has been the most difficult to
      determine and here is specified as the third electron transfer step. This
      reaction sequence is unchanged in the presence of tightly bound cytochrome c,
      although cytochrome c is rapidly oxidized via CuA and cytochrome alpha. The
      linear model advanced here has CuA as the acceptor of electrons from cytochrome
      c, with cytochrome alpha serving as a bridge to deliver electrons from CuA (and
      cytochrome c) to the binuclear center, cytochrome alpha 3-CuB.

PMID- 8300569
TI  - Phosphatidylinositol-anchored molecules and inducible lipopolysaccharide binding
      sites of human and mouse bone marrow cells.
AB  - We have previously established that lipopolysaccharide (LPS) induces the
      expression of new specific LPS-binding sites (LpsR) in mouse bone marrow cells
      (BMC). We now show that exposure of human BMC to LPS elicits the production of
      both CD14 molecules (detectable with monoclonal antibody My4) and LpsR
      (detectable with fluorescein isothiocyanate-LPS). Pretreatment of stimulated
      human BMC with My4 inhibited the binding of fluorescein isothiocyanate-LPS. The
      stimulation of human BMC, but not mouse BMC, required the presence of serum.
      Other characteristics of mouse and human BMC examined were very similar. Their
      inducible LpsR interacted with the lipid moieties of LPS and Leishmania donovani
      lipophosphoglycan and with a soluble preparation of peptidoglycan. Moreover,
      mouse and human LpsR were susceptible to treatment with a phosphatidylinositol
      specific phospholipase C (PI-PLC), thus suggesting that both are PI-anchored CD14
      molecules. Neither LpsR appeared able to interact with a synthetic LPS antagonist
      (compound PPDm2) structurally related to the lipid region of LPS. However, PPDm2
      blocked LPS-induced expression of LpsR in both BMC. Furthermore, in both species,
      pretreatment of BMC with PI-PLC did not prevent the cells from expressing LpsR in
      response to LPS. The results support the hypothesis that the elicited LpsR of
      mouse and human BMC is an inducible form of CD14, whereas the putative "signaling
      LPS receptor" of these cells is not CD14 or any other PI-anchored molecule.

PMID- 8300570
TI  - Identification of a mutant human topoisomerase I with intact catalytic activity
      and resistance to 9-nitro-camptothecin.
AB  - Human U-937 myeloid leukemia cells were selected for resistance to increasing
      concentrations of the camptothecin derivative, 9-nitro-20(S)camptothecin (9-NC).
      The isolated single cell clone, designated U-937/CR, was approximately 20-fold
      resistant to 9-NC. Analysis of topoisomerase I (topo I) gene expression in U
      937/CR cells demonstrated similar mRNA levels as compared with U-937 cells.
      Immunoblotting with an anti-topo I serum revealed reactive proteins at 100, 75,
      and 67 kDa which were expressed at the same level in the parental and 9-NC
      resistant clones. These cell lines also demonstrated similar levels of topo I
      catalytic activity as determined by assaying nuclear extracts for relaxation of
      supercoiled plasmid DNA. In contrast, catalytic assays performed in the presence
      of 9-NC demonstrated that topo I activity from U-937/CR cells was approximately
      10-fold more resistant than that from U-937 cells. Nucleotide sequencing of topo
      I cDNAs revealed the substitution of phenylalanine (TTC) at residue 361 in U-937
      cells with serine (TCC) in the 9-NC-resistant clone. Expression and partial
      purification of the mutant topo I protein in Escherichia coli demonstrated
      resistance of this enzyme to 9-NC in catalytic assays. Taken together, these
      findings identify a novel mutation in topo I which confers resistance to 9-NC and
      support the involvement of this region in the interaction between topo I and 9
      NC.

PMID- 8300571
TI  - Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the
      amino terminus and overall sequence similarity to prepro-von Willebrand factor.
AB  - Secretory mucins consist of a protein backbone that is catenated by disulfide
      bonds, heavily O-glycosylated, and packaged into storage granules prior to
      release from cells. In this paper, we identify and sequence cDNAs that encode the
      amino terminus of the MUC2 protein, a major form of mucin found in human
      intestines and airways. The protein sequence was found to contain a repetitive
      element of approximately 350 amino acids with considerable sequence similarity to
      the D domains of prepro-von Willebrand factor. A total of four of these D domains
      were found to be present in the MUC2 protein, three in the amino-terminal region,
      and one in the carboxyl-terminal region. Prepro-von Willebrand factor contains
      four D domains itself, and the overall positioning of the D domains in the two
      proteins is similar. Prepro-von Willebrand factor contains a 741 residue pro
      protein that has been implicated in both the disulfide-linked oligomerization of
      von Willebrand factor and its packaging into secretory vacuoles. A similar region
      is present in the MUC2 amino terminus sequence, suggesting that the mechanisms
      involved in the polymerization and packaging of MUC2 may parallel those already
      described for von Willebrand factor.

PMID- 8300572
TI  - Expression of the trans-active factors that stimulate insulin control element
      mediated activity appear to precede insulin gene transcription.
AB  - Cell type-specific expression of the major differentiated products of alpha
      (glucagon) and beta (insulin) cells are regulated by sequences found within their
      5'-flanking region. Specific transcription of the insulin gene appears to be
      principally controlled by a single cis-acting DNA element, termed the insulin
      control element (ICE). The ICE activator acts in combination with other positive
      regulatory factors that interact within this region to generate the correct, cell
      type-specific expression. In the present study, we show that the ICE activator is
      not only present but is functionally active in the islet glucagon-producing alpha
      cell line, alpha TC6. Analysis of the expression of various transfected insulin
      enhancer expression plasmids demonstrated that the insulin enhancer is active in
      alpha TC6 cells, although at a lower level than in beta cells. The reduced
      transcription from these constructs appears to be a consequence of the lack of
      other essential positive regulator(s). The alpha TC6 cells were also shown to
      display neuronal-like properties. Since islet cells appear to evolve from an
      alpha-like precursor cell that transiently expresses neuronal cell markers, these
      results would indicate that the ICE activator factor is induced before
      transcription of the insulin gene in the developing islet.

PMID- 8300573
TI  - Myogenin and acetylcholine receptor alpha gene promoters mediate transcriptional
      regulation in response to motor innervation.
AB  - Several genes expressed in skeletal muscle are transcriptionally repressed by
      electrical activity arising from motor innervation and are rapidly induced
      following denervation. Among these are genes encoding the subunits of the
      nicotinic acetylcholine receptor (AChR) and the myogenic helix-loop-helix protein
      myogenin, which activates muscle-specific genes. To understand how electrical
      activity arising from motor innervation is converted into a transcriptional
      response, we have attempted to localize cis-acting sequences in the AChR alpha
      subunit and myogenin genes sufficient to direct activity-dependent transcription.
      Here we show that an 111-base pair and a 335-base pair region from the promoters
      of the AChR alpha subunit and myogenin genes, respectively, can confer activity
      dependent regulation to a linked reporter gene in transgenic mice. The presence
      of binding sites for myogenic helix-loop-helix proteins in both of these
      regulatory regions is consistent with the hypothesis that these myogenic
      regulators serve as nuclear targets for the signaling cascade through which motor
      innervation leads to changes in gene transcription in skeletal muscle.

PMID- 8300574
TI  - Primary structure and transcription of genes encoding B870 and photosynthetic
      reaction center apoproteins from Rubrivivax gelatinosus.
AB  - We determined the nucleotide sequence of the puf operon of Rubrivivax gelatinosus
      (formerly called Rhodocyclus gelatinosus), a photosynthetic bacterium belonging
      to the beta subclass of purple bacteria (proteobacteria). The operon contains two
      unknown open reading frames (ORFs) in addition to five photosynthetic genes which
      have been reported in species belonging to the alpha subclass. These genes
      include pufB, -A, -L, -M, and -C coding for the beta and alpha subunits of the
      B870 light-harvesting protein and for the L, M, and cytochrome subunits of the
      reaction center complex, respectively. One (ORF1) of the two unknown ORFs locates
      immediately upstream of pufB, while the other (ORF2) locates between pufB and
      pufA. The deduced product of ORF1 is a small basic protein composed of 41 amino
      acids that did not show homology with any other proteins reported to date. The
      deduced product of ORF2 was composed of 74 amino acids having a hydrophobic
      region able to span the membrane and showed homology with the beta subunit of
      B870. The deduced amino acid sequence of the cytochrome subunit of the reaction
      center of R. gelatinosus had significant deletions in the possible attachment
      site to the M subunit compared with that of Rhodopseudomonas viridis. This is
      consistent with the facilitated dissociation of this subunit observed with
      detergent treatment in R. gelatinosus. Analysis of RNA from R. gelatinosus showed
      that the puf operon of this bacterium has two transcripts; the major one is 1
      kilobase in length and the minor one is 4 kilobase in length. These two
      transcripts have the same 5'-end, and their stoichiometry appeared to be
      controlled by a putative hairpin structure between pufA and pufL.

PMID- 8300575
TI  - Expression and activation of cdks (1 and 2) and cyclins in the cell cycle
      progression during liver regeneration.
AB  - In normal adult liver, hepatocytes are arrested in G0, and they rapidly respond
      to a mass loss by a definite number of divisions. Thus, taking advantage of the
      in vivo regenerative capacity of the liver following partial hepatectomy, we have
      analyzed both expression and activation of p34cdc2 (= cdk1) and p33cdk2 through
      the cell cycle, particularly during the long lasting G1 phase and in the G1/S
      transition. While p33cdk2 is constantly expressed during the cell cycle, p34cdc2
      is completely absent in resting hepatocytes and remains unexpressed for up to 20
      h after partial hepatectomy, a time period corresponding to the G1 phase and G1/S
      transition, and then accumulates in the S, G2, and M phases. No histone H1 kinase
      activity is detected during the G1 phase, while two peaks of p34cdc2 kinase
      activity are observed during the S and M phases and only one peak of p33cdk2
      kinase activity in the S phase. p34cdc2 forms complexes with both cyclins A and B
      while p33cdk2 is associated with cyclin A only. Surprisingly, cyclins E and D1
      are present in resting liver and with modest variation throughout the cell cycle.
      Taken together, our data provide evidence that the pattern of G1-associated
      proteins in hepatocytes during liver regeneration is distinct from that described
      in other cell types.

PMID- 8300576
TI  - Effects of CaBP2, the rat analog of ERp72, and of CaBP1 on the refolding of
      denatured reduced proteins. Comparison with protein disulfide isomerase.
AB  - It has been shown previously that CaBP2, the rat analog of the murine protein
      ERp72, and CaBP1, the rat analogue of the hamster protein P5, represent members
      of the protein disulfide isomerase (PDI) family and are able to catalyze the
      reduction of insulin in the presence of various reductants (Nguyen Van et al.,
      1993). We have now examined the abilities of CaBP2 and CaBP1 to catalyze the
      renaturation of denatured reduced model proteins. Both CaBP2 and CaBP1 catalyzed
      the reappearance of the biological activity of the denatured reduced Fab fragment
      of a monoclonal anti-human creatine phosphokinase antibody. The reaction rate was
      positively correlated with the amount of CaBP2 or CaBP1 and dependent on the
      GSH/GSSG ratio (maximum at GSH/GSSG = 1). Peptide prolyl-cis,trans-isomerase
      (PPI), which catalyzed some renaturation on its own, showed synergistic effects
      with PDI, CaBP2, and CaBP1. No synergistic effects could be observed when the
      combinations CaBP2 + PDI, CaBP1 + PDI, or CaBP2 + CaBP1 were tested. Variation of
      [Ca2+] between 0 and 1 mM did not have any effect on the rate or amount of
      renaturation catalyzed by CaBP2, CaBP1, or PDI, nor were these parameters
      affected by the simultaneous presence of BiP or grp94. Both CaBP2 and CaBP1
      catalyzed also the renaturation of denatured reduced ribonuclease AIII in a way
      that depended on the amounts of CaBP2 or CaBP1 and on the redox potential of the
      redox system used (GSH/GSSG or CSH/CSSC). PPI alone had no effect on the rate of
      RNase AIII renaturation and did not significantly affect renaturation catalyzed
      by PDI, CaBP2, or CaBP1. PDI showed a moderate but significant synergism with
      CaBP2, and a strong synergism with CaBP1. The results indicate that both CaBP2
      and CaBP1 can catalyze the formation of disulfide bonds and protein disulfide
      isomerization and may thus be involved in the folding of nascent proteins in the
      secretory pathway. This does not exclude the possibility of additional functions
      of these proteins in the pre-Golgi compartments.

PMID- 8300577
TI  - Effect of fatty acids on H+ transport activity of the reconstituted uncoupling
      protein.
AB  - A detailed study on the activation of H+ transport by reconstituted uncoupling
      proteins from brown adipose tissue is given, including the influence of chain
      lengths and of other structural modifications, concentration dependence, and the
      influence of nucleotides. Uncoupling protein was reconstituted with
      phosphatidylcholine in such a way as to keep H+ transport with endogenous fatty
      acids at a minimum. Using excess of polystyrene beads on reconstitution avoided
      the complications arising from the use of albumin. Both delta psi-driven H+
      uptake and H+ efflux systems are used by changing the polarity. Fatty acids
      stimulate H+ uptake up to 6-fold and H+ efflux more than 10-fold. There is no
      competition between the inhibition by nucleotides (GTP) and fatty acids. Also,
      the binding of GTP and ATP is not affected. Only fatty acids starting from C8
      activate, reaching a maximum at C14. However, unsaturated homologous of C18
      (oleic, linoleic, etc.) are fully active. Hydrophilic substitutions by hydroxyl,
      CO2H, bromo, doxyl groups also permit good activation, probably due to improved
      uptake into the lipid phase. The hydrophobic moiety exhibits a low specificity.
      Blockage of carboxyl by esterification abolishes the activation. Maximum
      activation requires high total concentrations of 200-300 microM. The distribution
      of fatty acids between proteoliposomes and solution was determined. The
      activation mode of fatty acids is discussed either as regulatory activators or as
      cofactors in H+ translocation involving their carboxyl groups. Two alternatives
      are considered, namely that the fatty acids carboxyl group is at the
      translocation center or in the channel facilitating H+ transfer to the
      constituent H(+)-translocating carboxyl groups.

PMID- 8300578
TI  - Dexamethasone down-regulation of insulin receptor substrate-1 in 3T3-L1
      adipocytes.
AB  - Insulin resistance resulting from prolonged exposure of intact animals or
      cultured cells to glucocorticoids is often attributed to postreceptor signaling
      defects. To better understand the specific effects of glucocorticoids on insulin
      signaling, we have characterized the effect of dexamethasone on the expression of
      an insulin signaling intermediate, the insulin receptor substrate-1 (IRS-1) in
      3T3-L1 adipocytes. Addition of dexamethasone resulted in a 40-70% decline in
      steady-state IRS-1 protein over 24-48 h of treatment. Dexamethasone did not
      significantly change the degradation rate of IRS-1 protein but decreased the net
      rate of amino acid incorporation into IRS-1 by 87%. Between 1 and 2.5 h of
      treatment with dexamethasone, actinomycin D, or both drugs given simultaneously,
      the concentration of IRS-1 mRNA declined with a half-life of 0.7-1.0 h. However,
      after 4 h of dexamethasone treatment, IRS-1 mRNA concentrations stabilized at
      approximately 35% of the control level. The dexamethasone-induced decline in IRS
      1 protein could be prevented by simultaneous administration of the glucocorticoid
      antagonist mifepristone, RU38486. These results suggest that in 3T3-L1 adipocytes
      the loss of IRS-1 protein after dexamethasone treatment can be accounted for
      chiefly by inhibition of the synthesis of IRS-1 mRNA.

PMID- 8300579
TI  - 19F and 13C NMR studies of polyol metabolism in freeze-tolerant pupae of
      Hyalophora cecropia.
AB  - Sorbitol biosynthesis and regulation in freeze tolerant pupae of Hyalophora
      cecropia have been investigated as a function of temperature by 19F and 13C
      nuclear magnetic resonance (NMR) spectroscopy using several 13C-labeled and/or
      fluorine-substituted carbohydrates. 3-Deoxy-3-fluoro-D-glucose (3DFG) was
      metabolized to 3-deoxy-3-fluoro-D-sorbitol (3DFS), 3-deoxy-3-fluoro-D-fructose
      (3DFF), and 3-deoxy-3-fluoro-D-gluconic acid (3DFGA), indicating that the enzymes
      required for sorbitol biosynthesis and metabolism are active in H. cecropia at
      warm (22 degrees C) and cold (4 and -10 degrees C) temperatures. Two additional
      metabolites were produced when pupae were injected with either 3DFG, 3DFS, 3DFF,
      or 3-deoxy-3-fluoro-D-mannose (3DFM). One of these was identified as 3-deoxy-3
      fluoro-D-mannitol (3DFML) by 13C NMR using [1-13C]3DFM and [1-13C]3DFG as
      metabolic probes. H. cecropia pupae injected with D-glucose labeled with 13C at C
      1, C-2, or C-3 and subsequently analyzed by 13C NMR clearly demonstrated the
      ability to generate sorbitol and fructose. In contrast, gas chromatography/mass
      spectrometric analysis of hemolymph failed to detect sorbitol in pupae reared
      under natural conditions (i.e. in the absence of injected enriched sugars). Thus,
      although H. cecropia pupae have the enzymic machinery to biosynthesize sorbitol,
      they do not appear to accumulate high steady-state concentrations of this polyol
      over the temperature range studied. The specificity of the enzymes involved in
      alditol biosynthesis in H. cecropia was examined by 13C NMR with a wide range of
      aldoses enriched with 13C at C-1. Pupae were capable of converting these sugars
      to their corresponding [1-13C]alditols, indicating that nonspecific
      dehydrogenase(s), in addition to aldose reductase, is(are) involved in polyol
      biosynthesis in H. cecropia pupae.

PMID- 8300580
TI  - Reverse transphosphorylation by ribonuclease A needs an intact p2-binding site.
      Point mutations at Lys-7 and Arg-10 alter the catalytic properties of the enzyme.
AB  - Bovine pancreatic ribonuclease A interacts with RNA along multiple binding
      subsites that essentially recognize the negatively charged phosphates of the
      substrate. This work gives additional strong support to the existence of the
      postulated phosphate-binding subsite p2 (Pares, X., Llorens, R., Arus, C., and
      Cuchillo, C. M. (1980) Eur. J. Biochem. 105, 571-579) and confirms the central
      role of Lys-7 and Arg-10 in establishing an electrostatic interaction with a
      phosphate group of the substrate. The effects of charge elimination by Lys-7-
      >Gln (K7Q) and/or Arg-10-->Gln (R10Q) substitutions in catalytic and ligand
      binding properties of ribonuclease A have been studied. The values of Km for
      cytidine 2',3'-cyclic phosphate and cytidylyl-3',5'-adenosine are not altered but
      are significantly increased for poly(C). In all cases, kcat values are lower.
      Synthetic activity, i.e. the reversion of the transphosphorylation reaction, is
      reduced for K7Q and R10Q mutants and is practically abolished in the double
      mutant. Finally, the extent of the reaction of the mutants with 6-chloropurine-9
      beta-D-ribofuranosyl 5'-monophosphate indicates that the phosphate ionic
      interaction in p2 is weakened. Thus, p2 modification alters both the catalytic
      efficiency and the extent of the processes in which an interaction of the
      phosphate group of the substrate or ligand with the p2-binding subsite is
      involved.

PMID- 8300581
TI  - A protein S binding site on C4b-binding protein involves beta chain residues 31
      45.
AB  - C4b-binding protein (C4BP) down-regulates the anticoagulant cofactor activity of
      protein S in the protein C pathway since free protein S but not the protein
      S:C4BP complex is anticoagulantly active. To identify beta chain residues
      responsible for binding protein S, synthetic overlapping pentadecapeptides
      covering the entire 1-235 sequence were tested as inhibitors of complex
      formation. The peptide comprising residues 31-45 (VCIKGYHLVGKKTLF) from the first
      short consensus repeat domain inhibited the binding of C4BP to protein S with
      half-maximal inhibition at 20-45 microM, and studies suggested the sequence of
      YxLVG was crucial. Peptide beta(31-45) specifically inhibited the APC cofactor
      activity of purified protein S in Xa-1-stage coagulation assays with 50%
      inhibition at 15 microM peptide. Peptide beta(31-45) and related peptides such as
      beta(34-42) inhibited the binding of protein S to an antipeptide monoclonal
      antibody made against residues 420-434 of protein S (monoclonal antibody LJ-56).
      Polyclonal anti-beta(31-45) peptide antibodies inhibited complex formation. Dose
      dependent binding studies showed that protein S bound directly to immobilized
      peptide beta(31-45). These results show that residues 31-45 of the C4BP beta
      chain provide a binding site for protein S, and they suggest that the C4BP beta
      chain residues 34-42 are located near residues 420-434 of protein S in the
      protein S:C4BP complex.

PMID- 8300582
TI  - Characterization of sequences within heparin-binding EGF-like growth factor that
      mediate interaction with heparin.
AB  - Heparin-binding (HB) epidermal growth factor (EGF)-like growth factor (HB-EGF), a
      member of the EGF protein family, is a potent mitogen for fibroblasts, smooth
      muscle cells, and keratinocytes that was initially identified as a secreted
      product of macrophage-like cells. HB-EGF and EGF appear to act on target cells
      utilizing the same receptor, but HB-EGF is distinguishable from EGF by its strong
      affinity for heparin. To facilitate studies of structure-function relationships
      in HB-EGF, a bacterial recombinant expression system was established that
      produced biologically active HB-EGF with the expected disulfide bonding pattern.
      Mutagenesis and protease digestion studies of the recombinant HB-EGF, coupled
      with heparin-binding analyses of synthetic peptides, indicated that the sequences
      within HB-EGF mediating its interaction with heparin are located primarily in a
      stretch of 21 amino acids characterized by a high content of lysine and arginine
      residues. Most of this heparin-binding domain lies in an amino-terminal region of
      HB-EGF that has no counterpart in EGF, but a portion of the 21-residue sequence
      extends into the EGF-like region of HB-EGF. In addition, the mutagenesis and
      synthetic peptide studies indicated that sequences in HB-EGF lying outside of the
      21-residue stretch can also influence the interaction with heparin. Finally, a
      synthetic peptide derived from the 21-residue stretch was found to compete with
      HB-EGF for binding to Chinese hamster ovary cells, suggesting that the heparin
      binding sequences in HB-EGF may also mediate the interaction of this factor with
      cell surface heparan sulfate proteoglycan.

PMID- 8300583
TI  - Enhanced gene delivery and mechanism studies with a novel series of cationic
      lipid formulations.
AB  - The application of cationic liposome reagents has advanced DNA and mRNA
      transfection research in vitro, and data are accumulating which show their
      utility for in vivo gene transfer. However, chemical structure-activity data
      leading to a better mechanistic understanding of their biological activity is
      still limited. Most of the cationic lipid reagents in use today for this
      application are formulated as liposomes containing two lipid species, a cationic
      amphiphile and a neutral phospholipid, typically dioleoylphosphatidylethanolamine
      (DOPE). The studies reported here examine the effects of some systematic chemical
      structural changes in both of these lipid components. Cationic and neutral
      phospholipids were formulated together as large multilamellar vesicles (MLV) or
      small sonicated unilamellar vesicles (SUV) in water, and each formulation was
      assayed quantitatively in 96-well microtiter plates under 64 different assay
      conditions using COS.7 cells and an RSV-beta-galactosidase expression plasmid.
      The cationic lipid molecules used for these studies were derived from a novel
      series of 2,3-dialkyloxypropyl quaternary ammonium compounds containing a
      hydroxyalkyl moiety on the quaternary amine. A homologous series of dioleylalkyl
      (C18:1) compounds containing increasing hydroxyalkyl chain lengths on the
      quaternary amine were synthesized, formulated with 50 mol % DOPE, and assayed for
      transfection activity. The order of efficacy was ethyl > propyl > butyl > pentyl
      > 2,3-dioleyloxypropyl-1-trimethyl ammonium bromide (DOTMA). DOTMA, which is
      commercially available under the trademark Lipofectin Reagent, lacks a
      hydroxyalkyl moiety on the quaternary amine. A homologous series of hydroxyethyl
      quaternary ammonium derivatives with different alkyl chain substitutions were
      synthesized, formulated with 50 mol % DOPE, and assayed in the transfection
      assay. The order of transfection efficacy was dimyristyl (di-C14:0) > dioleyl (di
      C18:1) > dipalmityl (di-C16:0) > disteryl (di-C18:0). The addition of 100 microM
      chloroquine in the transfection experiment enhanced the activity of the dioleyl
      compound by 4-fold and decreased the activity of the dimyristyl compound by 70%.
      For each of the compounds and formulations examined in this report, large
      multilamellar vesicles (MLV; diameter 300-700 nm) were more active than small
      unilamellar vesicles (SUV; diameter 50-100 nm). The neutral phospholipid
      requirements for transfection activity in COS.7 cells with these cationic lipid
      molecules were examined.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8300584
TI  - Transmembrane helix-helix interactions in F0 suggested by suppressor mutations to
      Ala24-->Asp/Asp61-->Gly mutant of ATP synthase subunit.
AB  - A mutant of ATP synthase subunit c was isolated in which the essential aspartate
      was exchanged from position 61 on transmembrane helix-2 to position 24 on
      transmembrane helix-1 (Miller, M. J., Oldenburg, M., and Fillingame, R. H. (1990)
      Proc. Natl. Acad. Sci. U. S. A. 87, 4900-4904). The H+ transporting ATP synthase
      function of the Ala24-->Asp/Asp61-->Gly mutant is not optimal, and cells grow
      more slowly than wild type. Twenty-three third-site suppressor mutants with
      optimized function were isolated in this study. Ten of the optimizing mutations
      were located to helix-2 of subunit c, and seven of these fell in residues Phe53,
      Met57, and Met65. The side chains of these three residues are proposed to form a
      hydrophobic surface on transmembrane helix-2, which participates in the
      presentation or occlusion of the essential aspartate carboxyl group during proton
      translocation. The other 13 optimizing mutations were located to subunit a, and
      10 of these fell in residues Ala217, Ile221, and Leu224. These three residues are
      proposed to lie on one face of a transmembrane alpha-helix that includes the
      essential Arg210 residue. This helix is proposed to interact with the
      transmembrane bihelical unit of subunit c during protonation and deprotonation of
      the essential Asp24 in the mutant or Asp61 in wild type.

PMID- 8300585
TI  - Mutations of tyrosine 82 in bovine adrenodoxin that affect binding to cytochromes
      P45011A1 and P45011B1 but not electron transfer.
AB  - To understand the function of the unique tyrosine in position 82 of bovine
      adrenodoxin (Adx), which had been proposed to be involved in electron transfer
      from NADPH-dependent adrenodoxin reductase (AdR) to cytochrome P-450 enzymes
      and/or AdR binding by chemical modification studies (Taniguchi, T., and Kimura,
      T. (1975) Biochemistry 14, 5573-5578), the residue was replaced by phenylalanine,
      leucine, or serine. Unchanged absorption, CD, and electron spin resonance spectra
      as well as redox potentials indicate that the environment of the [2Fe-2S] cluster
      was not affected by the mutations. The Vmax values in cytochrome c reduction,
      P45011A1- and P45011B1-dependent activities were also not changed when using
      Y82F, Y82S, and Y82L Adx mutants as electron donor, demonstrating that tyrosine
      82 is not involved in the intra- or intermolecular electron transfer. Replacement
      of tyrosine 82 did not affect AdR binding as shown by unchanged cytochrome c
      activity. There are, however, changes in Km values up to 4-fold when measuring
      the enzymatic activities of mutant Adx with P45011A1 and P45011B1. These changes
      differ in dependence on the P-450 (P45011A1 or P45011B1) used. The results
      suggest that mutation of tyrosine 82 either directly or indirectly (by inducing
      small conformational changes of the binding domain) affects the binding of
      cytochromes P-450.

PMID- 8300586
TI  - A new neurotoxin receptor site on sodium channels is identified by a conotoxin
      that affects sodium channel inactivation in molluscs and acts as an antagonist in
      rat brain.
AB  - The peptide conotoxin TxVIA is selectively toxic to molluscs and slows sodium
      current inactivation in mollusc neurons. Here we show that TxVIA binds with high
      affinity to new sites on sodium channels in both mollusc and rat central nervous
      systems, despite its lack of toxicity to vertebrates. Furthermore, TxVIA protects
      from the toxic effects of Conus striatus toxin in rat brain. The TxVIA binding
      site differs from other neurotoxin receptor sites affecting sodium channel
      inactivation in that binding is not voltage-dependent and undergoes negative
      allosteric modulation by veratridine. TxVIA therefore represents a novel category
      of sodium channel probes, designated delta-conotoxins. TxVIA is shown to
      discriminate between sodium channels in different phyla by activity but not by
      binding, thus providing a lead for the study of structural elements affecting
      gating modes of sodium channels.

PMID- 8300587
TI  - The binding properties of two antitumor ruthenium(III) complexes to
      apotransferrin.
AB  - The interaction of two ruthenium(III) complexes exhibiting high anticancer
      activity, namely trans-indazolium(bisindazole)tetrachlororuthenate(III) (ru-ind)
      and trans-imidazolium(bisimidazole)tetrachlororuthenate(III) (ru-im), with human
      serum apotransferrin has been investigated through spectroscopic and
      chromatographic techniques with the ultimate goal of preparing adducts with good
      selectivity for cancer cells. Whereas the binding of ru-im to human serum
      apotransferrin takes several hours, ru-ind, the less toxic complex, gives rise to
      a well defined 2:1 complex within a few minutes. We have ascertained that ru-ind
      binding occurs around the iron binding sites; binding does not occur in the
      absence of bicarbonate, and this anion dictates the kinetic and mechanistic
      characteristics of protein binding of ru-ind. The two ruthenium(III) complexes do
      not behave as iron(III) complexes, e.g. Fe(EDTA) or Fe(nitrilotriacetate), which
      lose their respective ligands when binding apotransferrin, but the N-heterocycles
      remain attached to the metal in the protein-bound species. Reversion of binding
      is obtained by acidification in the presence of chelators such as citrate or ATP.
      In comparison with cisplatin and its deactivation by serum proteins, our results
      indicate that other metal complexes such as ru-ind could use transferrin as a
      drug delivery system. Furthermore, the rapid protein binding of ru-ind seems to
      be related to a lower toxicity while still exhibiting high antitumor activity.

PMID- 8300588
TI  - Evidence that Na+/H+ exchanger isoforms NHE1 and NHE3 exist as stable dimers in
      membranes with a high degree of specificity for homodimers.
AB  - In this study, we have investigated whether members of the Na+/H+ exchanger (NHE)
      family are oligomers and whether such oligomeric structure is required for
      function. Fibroblasts overexpressing NHE1 were treated briefly at 0 degrees C
      with the cross-linker disuccinimidyl suberate, then membranes were prepared and
      proteins analyzed by SDS-polyacrylamide gel electrophoresis. Disuccinimidyl
      suberate treatment converted quantitatively the immunoreactive monomeric form of
      NHE1 (110 kDa) to a putative dimeric form (210 kDa). Utilization of NHE1 mutant
      deleted of the cytoplasmic domain (delta 515TH) demonstrates that the
      transmembrane domain of the antiporter is sufficient for dimerization. Moreover,
      coimmunoprecipitation of NHE1 and delta 515TH, coexpressed in the same cell,
      formally proved the existence of dimers. This dimerization was also shown to take
      place with the epithelial and apically expressed NHE3 isoform, suggesting that
      oligomerization is a common feature of these transporters. However, coexpression
      of NHE1 and NHE3 in the same cells did not lead to the formation of heterodimers
      demonstrating an isoform specificity for the subunit interaction. The domain(s)
      involved in the isoform-specific dimerization is (are) likely to be confined
      within the transmembrane segments, as deletion of the 300 amino acids of the
      cytoplasmic domain did not disrupt dimerization. Exploiting the dimeric
      properties of the receptor tyrosine kinases and the fact that dimerization
      triggers kinase activity, we constructed a NHE1/insulin receptor chimera to probe
      NHE1 dimerization in vivo. When transfected into hamster fibroblasts, this
      chimera containing the N-terminal transmembrane domain of NHE1 and the
      cytoplasmic beta-subunit domain of the insulin receptor generates a functional
      transporter that is autophosphorylated on tyrosine and that presents properties
      of a constitutively active insulin receptor. These findings support the notion
      that NHE1 exists in an oligomeric state in intact cells. Finally, to test whether
      individual subunits of NHE1 are the minimum functional unit for Na+/H+ exchange,
      we coexpressed a truncated form of NHE1 (delta 515) together with an inactive
      mutant of NHE1 (E262I). In spite of good expression of the inactive transporter
      and its capacity to dimerize with active NHE1, no dominant negative effect was
      observed on amiloride-sensitive 22Na+ flux. This observation would suggest that
      individual subunits of NHE1 function independently within the oligomeric state.

PMID- 8300590
TI  - Structure-activity studies of human sterol carrier protein 2.
AB  - Recombinant human sterol carrier protein 2 (SCP2) variants were generated by site
      directed mutagenesis and expression in Escherichia coli. The ability of the
      variants to stimulate microsomal conversion of 7-dehydrocholesterol to
      cholesterol (sterol carrier activity) and to transfer cholesterol and
      phosphatidylcholine from donor small unilamellar vesicles to acceptor membranes
      (cholesterol and phosphatidylcholine transfer activities) was compared with wild
      type recombinant SCP2. Our results indicate that all measured activities of
      recombinant human pre-SCP2 (including the 20-amino acid leader sequence) and
      mature SCP2 were similar. Expressed glutathione S-transferase fusion proteins
      (GST-SCP2 and GST-pre-SCP2) possessed considerable activity, suggesting that
      steric obstruction at the amino terminus causes only minor inactivation. The
      effect of progressive removal of peptides from the carboxyl terminus showed that
      amino acids between Lys100 and Asn104 are essential for SCP2 activity. This
      conclusion was substantiated by the observation that replacing Asn104 with Asp or
      Ile caused considerable inactivation, whereas replacing Met105 with Leu had
      almost no effect. Since N-ethylmaleimide is known to inhibit SCP2 activity,
      substitutions were also introduced in the vicinity of Cys71. Whereas Val71 and
      Ser71 variants possessed wild-type activity, replacing Asp70 with Asn almost
      completely abolished SCP2 activity. Further, the importance of residues located
      close to the amino terminus was indicated by complete inactivation of a 10-amino
      terminal amino acid deletion mutant and by replacing Leu20 with Glu. Circular
      dichroism results showed that Leu20 and Asp70 may serve to stabilize the overall
      fold, whereas residue 104 appears to play a role in the specific lipid binding
      and/or transfer activity of SCP2.

PMID- 8300589
TI  - Glycosylphosphatidylinositols synthesized by asexual erythrocytic stages of the
      malarial parasite, Plasmodium falciparum. Candidates for plasmodial
      glycosylphosphatidylinositol membrane anchor precursors and pathogenicity
      factors.
AB  - Plasmodium falciparum is the causative agent of malaria tropica in man.
      Biochemical studies were focused on the asexual, intraerythrocytic stages of P.
      falciparum, because of their role in the clinical phase of the disease and the
      possibility of propagation in a cell culture system. In this report, we describe
      the in-culture labeling of malarial glycolipids and the analysis of their
      hydrophilic moieties. They were identified as glycosylphosphatidylinositols
      (GPIs) by: 1) labeling with [3H]mannose, [3H]glucosamine, and [3H]ethanolamine
      and 2) sensitivity toward glycosylphosphatidylinositol-specific phospholipase D,
      phospholipase A2, and nitrous acid. Malarial GPIs are shown to be unaffected by
      treatment with phosphatidylinositol-specific phospholipase C, regardless of prior
      treatment with mild base commonly used for inositol deacylation. Two candidates
      for putative GPI-anchor precursors to malarial membrane proteins with the
      structures ethanolamine-phosphate-6(Man alpha 1-2)Man alpha 1-2Man alpha 1-6Man
      alpha 1-4 GlcN-PI (Pfg1 alpha) and ethanolamine-phosphate-6Man alpha 1-2Man alpha
      1-6Man-alpha 1-4-GlcN-PI (Pfg1 beta) were identified.

PMID- 8300591
TI  - Comparison and evolution of human immunoglobulin VH segments located in the 3'
      0.8-megabase region. Evidence for unidirectional transfer of segmental gene
      sequences.
AB  - Nucleotide sequences of 64 VH segments within the 3' 0.8-megabase region of the
      human immunoglobulin germ line VH locus were compared with trace evolution of
      human VH segments. Based on alignment of the deduced amino acid sequences of 37
      functional germ line VH segments, a phylogenetic tree was generated using the
      neighbor-joining method. The phylogenetic tree clearly supports the previous
      classification of human VH segments into six families, which correlate roughly
      with mouse VH families with varying conservation. The human VH-III family is most
      homologous to mouse VH segments, suggesting that members of the VH-III family may
      be conserved by some functional constraint. The 5'-flanking region of each family
      has a family-specific structure. The sequenced 64 VH segments include 31
      pseudogenes, of which 24 were highly conserved. Unidirectional transfer of
      segmental sequences was identified within the VH-III and VH-IV families,
      providing clear examples of germ line gene conversion. Such gene conversion may
      contribute to conserve structures of pseudo-VH segments. Comparison of the VH-IV
      family members indicates that recent repeated duplications and frequent gene
      conversions are responsible for strong conservation of this family, although
      functional selection is not completely excluded.

PMID- 8300592
TI  - Irreversible inactivation of 5-lipoxygenase by leukotriene A4. Characterization
      of product inactivation with purified enzyme and intact leukocytes.
AB  - We report that leukotriene A4, the electrophilic product of 5-lipoxygenase
      catalysis, irreversibly inactivates the enzyme. Leukotriene A4 inhibits 5
      hydroxyeicosatetraenoic acid formation by human neutrophils and differentiated
      granulocytic HL-60 cells in a concentration-dependent manner with IC50 values =
      22.4 +/- 2.5 and 29.0 +/- 8.0 microM, respectively. Recovery of cellular
      enzymatic activity is negligible (< 6%) following inactivation. Leukotriene A4
      inactivates cellular 5-lipoxygenase without inhibiting its translocation from the
      cytosol to the membrane, suggesting that it impairs catalysis without impairing
      formation of the complex between 5-lipoxygenase and its membrane-associated
      activating protein. Consistent with this, leukotriene A4 inactivates purified 5
      lipoxygenase from human neutrophils, via saturable, pseudo first-order kinetics
      with a rate constant, ki = 0.14 min-1 and a dissociation constant, Ki = 2.1 +/-
      0.7 microM. Purified 5-lipoxygenase incubated with [3H]arachidonic acid
      incorporated a radiolabeled species that was not removed by electrophoresis under
      reduced denaturing conditions. Preincubation with leukotriene A4 diminished the
      incorporation of radiolabeled material, consistent with irreversible modification
      of 5-lipoxygenase by its metastable product, leukotriene A4. This unusual product
      inactivation mechanism may contribute to the decline in 5-lipoxygenase activity
      observed during catalysis.

PMID- 8300593
TI  - Cloning and expression of a cDNA for the human prostanoid FP receptor.
AB  - A cDNA clone coding for a functional human prostanoid FP receptor has been
      isolated from a uterus cDNA library. The human FP receptor consists of 359 amino
      acid residues with a predicted molecular mass of 40,060, and has the seven
      putative transmembrane domains characteristic of G-protein-coupled receptors.
      Challenge of Xenopus oocytes expressing the FP receptor with 10 nM of either
      prostaglandin (PG) F2 alpha or the selective FP-receptor agonist fluprostenol
      resulted in an elevation in intracellular Ca2+. Radioreceptor binding studies
      using membranes prepared from mammalian COS cells transfected with the FP
      receptor cDNA showed that the rank order of potency for prostaglandins and
      prostaglandin analogs in competition for [3H]PGF2 alpha specific binding sites
      was as predicted for the FP receptor, with PGF2 alpha approximately fluprostenol
      > PGD2 > PGE2 > U46619 > iloprost. In summary, we have cloned the human
      prostanoid FP receptor which is functionally coupled to the Ca2+ signalling
      pathway.

PMID- 8300594
TI  - Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid
      precursor protein (APP).
AB  - Alzheimer's disease is characterized by the presence of senile plaques comprised
      primarily of deposits of the beta-amyloid protein (A beta) derived from larger
      amyloid precursor proteins (APP). We have identified a cDNA that encodes a 751
      amino acid APP-like protein (designated APLP2) from the mouse that, with
      exception of the A beta region, is highly homologous to APP. In situ
      hybridization and quantitative polymerase chain reaction reveal that APLP2 and
      APP mRNA are expressed in similar, if not identical, neuronal populations and at
      similar levels. APLP2 appears to mature through the same unusual
      secretory/cleavage pathway as APP. Furthermore, widely utilized antibodies
      generated against non-overlapping epitopes of APP do not discriminate between APP
      and APLP2. Although APLP2 cannot give rise to A beta, its near identity to APP
      outside the A beta domain confounds the interpretation of previous
      immunocytochemical and biochemical characterizations of APP biosynthesis and
      metabolism.

PMID- 8300595
TI  - Mutants of Agrobacterium VirA that activate vir gene expression in the absence of
      the inducer acetosyringone.
AB  - In the presence of inducer molecules produced by wounded plants, the VirA/VirG
      two-component positive regulatory system of Agrobacterium tumefaciens initiates
      transcription of virulence genes required for crown gall tumor formation. Exactly
      how this system enables the bacterium to respond to an environmental signal is
      not known, but phosphorylation of VirA and VirG plays a role. To analyze further
      the function of VirA, we chemically mutagenized the virA gene. Two mutants that
      activate vir transcription without the plant inducer acetosyringone were found;
      these mutants alter VirA function by distinct mechanisms. One mutant functions
      entirely independently of acetosyringone, whereas the activity of the second
      mutant is enhanced by acetosyringone. Both mutants function best at acid pH, but
      respond differently to specific monosaccharides that stimulate induction by wild
      type VirA. Both mutant phenotypes are dominant over wild-type VirA, and both need
      the conserved histidine at the autophosphorylation site for strong inducer
      independent vir transcription.

PMID- 8300596
TI  - Recombinant hybrid toxin with dual enzymatic activities. Potential use in
      preparing highly effective immunotoxins.
AB  - Bacterial toxins and ribosomal inhibitory proteins isolated from plants are used
      to prepare tumor-specific cytotoxic conjugates. The ability of these conjugates
      to kill tumor cells depends on binding, internalization, translocation to
      cytoplasm, and translation inhibition. Modulation of any one of these processes
      can improve cytotoxicity. Since bacterial and plant toxins act at a distinct step
      in translation, a combination of their activities could be more effective.
      Therefore, a chimeric protein was prepared by genetically fusing the coding
      region of the ricin A chain (RTA) and the fragment A of diphtheria toxin (DTA).
      The hybrid protein (RTA-DTA) expressed in bacteria retained the N-glycosidase
      activity of the RTA and ADP-ribosylation activity of the DTA. The hybrid toxin
      was more potent than the ricin A chain (11-fold) and the diphtheria toxin (50
      fold) in inhibiting cell-free translation. Immunotoxin made with the hybrid toxin
      was about 100- and 1000-fold more effective than RTA or DTA conjugate,
      respectively, in inhibiting tumor cell growth in vitro. These results indicate
      that the hybrid toxin with dual activities could be useful in preparing potent
      immunotoxins with better anti-tumor cell activity.

PMID- 8300597
TI  - Thermostable inhibitor of cAMP-dependent protein kinase enhances the rate of
      export of the kinase catalytic subunit from the nucleus.
AB  - The catalytic (C) subunit of cAMP-dependent protein kinase is inhibited by the
      regulatory (R) subunit and by a thermostable inhibitor (PKI). Both inhibitors
      also affect the intracellular distribution of the C subunit. Whether injected
      into the cytoplasm or into the nucleus, free C subunit can enter and exit the
      nucleus freely. After 30 min its distribution is identical and is independent of
      the initial site of injection. In contrast, when C is injected into the cytoplasm
      complexed with R or PKI, the complexes are restricted to the cytoplasm (1-3).
      However, unlike the R subunit, which is restricted to the cytoplasm like the
      holoenzyme, free PKI enters the nucleus rapidly following its injection into the
      cytoplasm. When holoenzyme is injected directly into the nucleus, it cannot exit
      and return to the cytoplasm. In contrast, nuclear injection of a C.PKI complex
      results in the rapid exit of the C subunit from the nucleus. In equilibrated
      cells previously injected with the C subunit, subsequent cytoplasmic injection of
      either PKI or type 1 R depletes the nucleus of C although PKI does so faster,
      consistent with its ability to enter the nucleus. Both inhibitors block the cAMP
      response element-regulated gene expression. Hence PKI may serve as a nuclear
      scavenger of C providing a mechanism not only for inhibition but also for
      subcellular localization in the presence of cAMP by restricting the access of the
      C subunit to the nucleus.

PMID- 8300599
TI  - Effects of nerve growth factor on rat peritoneal mast cells. Survival promotion
      and immediate-early gene induction.
AB  - Purified rat peritoneal mast cells in vitro die over a period of 2-6 days in
      conventional serum-containing medium. As mast cells die, they become pyknotic and
      undergo DNA fragmentation suggestive of an apoptotic process. Treatment of in
      vitro mast cells with nerve growth factor (NGF) greatly retards and reduces the
      death of mast cells (EC50 approximately 1 nM), with no effect on mast cell
      proliferation. Other neurotrophins have no such effect. NGF also induces the
      immediate early genes c-fos and NGFI-A with a similar dose dependence. In
      contrast to the secretagogue activity of NGF, neither the survival-promoting
      effect nor immediate early gene induction requires lysophosphatidylserine. The
      ability of NGF to promote mast cell survival is cell density-dependent and
      appears to be primarily because of induction of the synthesis and/or secretion of
      an autocrine survival factor by stimulated mast cells. These results suggest that
      the previously observed effects of NGF on mast cell numbers in vivo may in part
      be because of enhanced survival and that NGF may be an important mediator of mast
      cell function in normal and pathological states.

PMID- 8300598
TI  - Perturbing the metal site in D-xylose isomerase. Effect of mutations of His-220
      on enzyme stability.
AB  - The histidine residue at position 220 in the Streptomyces rubiginosus D-xylose
      isomerase is conserved in all D-xylose isomerases. The three-dimensional
      structure of D-xylose isomerase reveals that His-220 is part of the octahedral
      coordination sphere of M2, one of two metal ions (Mn2+) in the active site. This
      work describes the effects of replacing His-220 with Ser, Glu, Asn, and Lys. The
      consequences of these amino acid substitutions on enzyme activity,
      thermostability, and structure were analyzed by kinetic, denaturation, and
      crystallographic methods. The kcat values H220S, H220N, and H220E are only 0.3
      0.5% of the wild-type values, and the Km for each of these mutant enzymes
      increased by 30-40-fold over the wild-type value. The mutant enzyme H220K did not
      exhibit any measurable activity. Thermal denaturation studies (Tm values)
      indicate that the H220S and H220N mutant enzymes are approximately 5-8 degrees C
      less stable than the wild-type enzyme, whereas H220E and H220K are 13-24 degrees
      C less stable than the wild-type enzyme. To analyze the molecular basis for this
      decreased thermostability, the crystal structures of the H220S, H220N, and H220E
      mutant enzymes complexed with Mn2+ have been determined at 1.95, 1.90, and 1.75
      A, respectively. In the H220S structure, a water molecule effectively replaces
      the N epsilon-2 atom of the imidazole ring of His-220 and mediates the
      interaction between Mn2+ at the M2 site and Ser-220. A similar water-mediated
      interaction between the metal ion and Asn-220 is observed in H220N. No direct or
      water-mediated interactions between the carboxyl group of Glu-220 and the metal
      are observed in H220E. Whereas octahedral coordination is maintained for the
      metal at the M2 site in H220S and H220N, a pentahedral coordination with the
      metal at the M2 site is observed in H220E. Metal activation measurements support
      the observation that metal binding is perturbed and is responsible for thermal
      lability of His-220 mutants.

PMID- 8300600
TI  - Arginine decarboxylase of oats is activated by enzymatic cleavage into two
      polypeptides.
AB  - Oat arginine decarboxylase is synthesized as a 66-kDa proenzyme, but the soluble
      enzyme is found in oats as a complex of 42- and 24-kDa polypeptide fragments,
      both derived from the 66-kDa precursor. We report here that this proteolytic
      cleavage is the result of a processing enzyme, distinct from arginine
      decarboxylase itself, that leads to activation of the arginine decarboxylase. The
      proteolysis is resistant to a standard set of protease inhibitors, but is
      inhibited by high concentrations of Zn2+, as is the activation of arginine
      decarboxylase. Agmatine, putrescine, spermidine, and spermine, as well as the
      arginine decarboxylase inhibitor difluoromethylarginine, each had no effect on
      the reaction. Oat arginine decarboxylase is thus similar to some other amino acid
      decarboxylases in requiring a proteolytic cleavage for activation; however, it
      differs in that the other examples are auto-catalytic self-processing.

PMID- 8300601
TI  - Structural and functional aspects of basic helix-loop-helix protein folding by
      heat-shock protein 90.
AB  - The assembly and folding of nascent polypeptides are mediated in vivo by
      molecular chaperones, many of which are members of the heat-shock family of
      proteins. We have shown previously that heat-shock protein 90 (HSP90) folds an
      inactive fraction of a recombinant basic helix-loop-helix (bHLH) protein
      generated in Escherichia coli (MyoD) into its active conformation. We show here
      that HSP90 also folds another bHLH protein (E12) and heterodimers of E12/MyoD
      into their active conformations. By purifying inactive heterodimers of E12/MyoD
      and subsequently rendering them active in binding DNA by treatment with HSP90, we
      show that one folding step mediated by HSP90 occurs after oligomerization of the
      bHLH protein monomers. A series of deletion mutants is used to identify the 48
      amino acid region of HSP90 that confers bHLH folding activity, which lies near
      the COOH terminus. This region is required for activation of DNA binding of MyoD
      and E12 homodimers and E12/MyoD heterodimers.

PMID- 8300602
TI  - Transport, function, and sorting of lactase-phlorizin hydrolase in Madin-Darby
      canine kidney cells.
AB  - Lactase-phlorizin hydrolase (LPH), a small intestinal brush-border glycoprotein,
      is synthesized as a single chain precursor (pro-LPH, M(r) = 215,000-230,000) that
      undergoes cleavage to the final mature form (LPHm, M(r) = 160,000 in the human).
      In the human and pig small intestine as well as in the colon carcinoma cell line
      Caco-2, this cleavage takes place intracellularly prior to insertion into the
      brush-border membrane. To assess the role of proteolytic cleavage on the
      transport, function, and sorting of LPH a stable Madin-Darby canine kidney cell
      line was generated which expresses LPH (denoted as MDCK-ML). Biosynthetic
      labeling experiments demonstrated that the transport kinetics and
      posttranslational processing pattern of LPH in this cell line are similar to
      those in intestinal cells. Moreover, the enzymatic activity was found to be
      indistinguishable from that of brush-border LPH (LPHm). The sorting of LPH was
      studied by biosynthetic labeling of cells grown on filters followed by cell
      surface immunoprecipitation. Here, we could demonstrate that the cleaved LPHm
      molecule was predominantly found at the apical membrane, whereas complex
      glycosylated uncleaved pro-LPH (pro-LPHc) was targeted to both domains, the
      apical as well as the basolateral. In pulse-chase experiments at 20 degrees C pro
      LPH was arrested in the trans-Golgi network, and cleavage to LPHm did not take
      place. By contrast, when the chase temperature was raised to 37 degrees C
      transport of pro-LPHc resumed, and cleavage to LPHm occurred. We conclude that
      the proteolytic cleavage of pro-LPHc to LPHm is a post-trans-Golgi network event
      and is most likely not implicated in the sorting of LPH by exposition of
      otherwise masked sorting elements.

PMID- 8300603
TI  - Ca(2+)-calmodulin-dependent phosphorylation of arginine in histone 3 by a nuclear
      kinase from mouse leukemia cells.
AB  - A Ca(2+)-calmodulin dependent histone 3 kinase was partially purified from a low
      salt (150 mM NaCl) nuclear extract of mouse leukemia cells by calmodulin
      Sepharose affinity chromatography. In vitro, the kinase activity transferred
      gamma-phosphate from ATP to histone 3 to form an acid-labile and alkaline-stable
      linkage. Under the assay conditions 1.8 mol of phosphate are incorporated per mol
      of histone 3. Upon modification of arginine residues with phenylglyoxal prior to
      phosphorylation, a considerable decrease in the amount of phosphate transferred
      to histone 3 was observed. Amino acid analysis revealed that H3 was
      phosphorylated on arginine residues. To identify the phosphorylated peptide(s),
      histone 3 was cleaved with cyanogen bromide prior to phosphorylation. The
      phosphorylated mixture was then separated by gel filtration high-performance
      liquid chromatography under denaturing conditions. Fragments I (N-terminal 10.3
      kDa peptide) and III (C-terminal 1.7-kDa peptide) were both phosphorylated. Amino
      acid sequencing further revealed that the molar yields of 3 of the 4 arginines
      present in the phosphorylated cyanogen bromide fragment III were reduced by a
      factor of about 10 compared with the corresponding arginines from the
      unphosphorylated fragment. In the case of fragment I, 25 cycles of Edman
      degradation revealed that the recovery of only arginine 2 was reduced by a factor
      of 20. The putative phosphorylation sites are arginines 2, 128, 129, and 131. The
      sequence information offered an indirect evidence that these arginines were the
      sites of phosphorylation. The kinase described in this report represents a first
      member of a potentially important new class of kinases which are Ca(2+)
      calmodulin dependent and which phosphorylate arginine.

PMID- 8300604
TI  - The role of histidine 265 in antagonist binding to the neurokinin-1 receptor.
AB  - Previous studies suggested that the antagonist binding site in the neurokinin-1
      receptor is composed of phylogenetically conserved residues, while
      phylogenetically divergent residues affect the conformation of the binding site.
      To test this hypothesis, we investigated the role of conserved residues in
      antagonist binding. Histidine 197 in the human receptor was found to interact
      with CP-96,345 but not RP67580. In addition, a nearby residue, histidine 265 of
      the human receptor, is required for the binding of RP67580 but not CP-96,345 or
      substance P. The interaction between residue 265 and RP67580 is consistent with a
      hydrogen bonding interaction. Analysis of several analogs of CP-96,345 revealed
      that histidine 265 of the human receptor is in proximity to the substituted
      benzyl moiety of CP-96,345, and can interact with other analogs of CP-96,345. In
      contrast to the human neurokinin-1 receptor, both histidine 197 and histidine 265
      in the rat neurokinin-1 receptor appear to interact with both CP-96,345 and
      RP67580. These results support a conformational difference between the antagonist
      binding sites of the rat and human neurokinin-1 receptors and provide a model for
      examining specific interactions between antagonists and the receptor.

PMID- 8300605
TI  - Promoter of the POU-M1/SGF-3 gene involved in the expression of Bombyx silk
      genes.
AB  - To characterize the transcription regulation of the POU-M1/SGF-3 gene, we have
      cloned a genomic DNA fragment encompassing the whole coding region and its
      flanking sequences. This gene does not contain any intron. The 5'-flanking region
      of the gene contains several interesting motifs, such as homeodomain-binding
      motifs, sequences resembling the transcriptional factor Sp1-binding site, and
      TGTTT motifs, but lacks some of the typical transcriptional regulatory sequences,
      such as TATA and CCAAT boxes. Transcriptional analysis of a series of deletion
      mutants of the gene in the nuclear extracts prepared from the middle silk gland
      of 2-day-old fifth instar larvae revealed the presence of multiple cis-regulatory
      elements located both upstream and downstream of the initiation site. One of
      these elements, the homeodomain-binding element, was identified to mediate
      negative regulation. By mobility shift assay using the POU-M1 specific
      antibodies, we found that this negative element interacts with the POU-M1/SGF-3.
      Transcription analysis in vitro using templates mutagenized in the PB region and
      one of the POU-M1 antibodies indicated that the PB region is an autoregulatory
      element responsible for SGF-3-dependent transcriptional repression.

PMID- 8300606
TI  - Protein kinase C modulates the insulin secretory process by maintaining a proper
      function of the beta-cell voltage-activated Ca2+ channels.
AB  - In the present study an attempt was made to further elucidate the molecular
      mechanisms whereby protein kinase C (PKC) modulates the beta-cell stimulus
      secretion coupling. Regulation of Ca2+ channel activity, [Ca2+]i, and insulin
      release were investigated in both normal pancreatic mouse beta-cells and in
      similar beta-cells deprived of PKC activity. [Ca2+]i was measured with the
      intracellular fluorescent Ca2+ indicator fura-2 and the Ca2+ channel activity was
      estimated by the whole cell configuration of the patch-clamp technique. To reveal
      the various isoenzymes of PKC present in the mouse beta-cell, proteins were
      separated by one-dimensional gel electrophoresis and Western blotting was
      performed. The production of inositol phosphates was measured by ion-exchange
      chromatography and insulin release was measured radioimmunologically. Acute
      stimulation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate resulted
      in suppression of both the carbamylcholine-induced increase in [Ca2+]i and
      production of inositol 1,4,5-trisphosphate. Under these conditions the increase
      in [Ca2+]i in response to glucose was similar to that found in control cells.
      When beta-cells were deprived of PKC, by exposure to 200 nM 12-O
      tetradecanoylphorbol-13-acetate for 24-48 h, there was an enhanced response to
      carbamylcholine. This response constituted increases in both the [Ca2+]i signal
      and production of inositol 1,4,5-trisphosphate. Interestingly, cells with down
      regulated PKC activity responded more slowly to glucose stimulation, when
      comparing the initial increase in [Ca2+]i, than control cells. On the other hand,
      the maximal increase in [Ca2+]i was similar whether or not PKC was present.
      Moreover, PKC down-regulated cells exhibited a significant reduction of maximal
      whole cell Ca2+ currents, a finding that may explain the altered kinetics with
      regard to the [Ca2+]i increase in response to the sugar. Both the alpha and beta
      1 forms of the PKC isoenzymes were present in the mouse beta-cell and were also
      subjected to PKC down-regulation. Hence, either of these isoenzymes or both may
      be involved in the modulation of phospholipase C and Ca2+ channel activity. Since
      insulin release under physiological conditions is critically dependent on Ca(2+)
      influx through the voltage-gated L-type Ca2+ channels, the kinetics of hormone
      release was expected to demonstrate a similar delay as that of the [Ca2+]i
      increase. Although not as pronounced, such a delay was indeed also observed in
      the onset of insulin release. There was, however, no effect on the total amounts
      of hormone released.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8300608
TI  - Bombesin, platelet-derived growth factor, and diacylglycerol induce selective
      membrane association and down-regulation of protein kinase C isotypes in Swiss
      3T3 cells.
AB  - Swiss 3T3 cells contain protein kinase C (PKC) isotypes alpha, delta, epsilon and
      zeta (Olivier, A. R., and Parker, P. J. (1992) J. Cell. Physiol. 152, 240-244).
      Acute stimulation of quiescent cells with the neuropeptide bombesin decreases the
      mobility of PKC-delta and PKC-epsilon on SDS-polyacrylamide gels. These slower
      migrating forms of PKC-delta and PKC-epsilon rapidly (within 1 s) and selectively
      are found associated with the Triton X-100-soluble membrane fraction. No change
      in the mobility or distribution of PKC-alpha or PKC-zeta is detected. Long-term
      treatment of cells with bombesin induces selective membrane association and down
      regulation of PKC-delta and PKC-epsilon (decreasing 70 and 65%, respectively). No
      change in the long-term distribution of PKC-alpha and PKC-zeta was detected.
      Bombesin did, however, increase PKC-alpha protein levels by 60% compared to
      control cells. PKC-zeta levels remained unchanged. Both the shift in mobility and
      down-regulation of PKC-delta and PKC-epsilon were only induced by mitogenic doses
      of bombesin. The potent mitogen platelet-derived growth factor induced similar
      effects on the PKC isotypes delta and epsilon. PKC-alpha and PKC-zeta levels were
      unaffected. Repeated doses of the synthetic diglyceride 1-oleoyl-2-acetyl-sn
      glycerol induced PKC-delta and PKC-epsilon down-regulation and stimulated the
      cells to divide. Again PKC-alpha and PKC-zeta levels were unaffected. These
      results show a correlation between the membrane association and down-regulation
      of PKC-delta and PKC-epsilon and the entry of cells into S phase.

PMID- 8300607
TI  - An unusual 30-kDa protein binding to the polyhedrin gene promoter of Autographa
      californica nuclear polyhedrosis virus.
AB  - Gel retardation assays using nuclear extracts from the Autographa californica
      nuclear polyhedrosis virus-infected Sf21 (Spodoptera frugiperda) insect cell line
      revealed a host factor (polyhedrin promoter-binding protein or PPBP) that binds
      to the polyhedrin gene promoter. A hexanucleotide sequence (AATAAA) within the
      promoter is important for binding in association with neighboring elements, some
      of which are contributed by the sequence TAAGTATT present at the transcription
      start point. PPBP was affinity purified and appears to be an unusual DNA-binding
      protein with respect to its stability (binding was obtained at NaCl
      concentrations and temperatures ranging from 0.2 to 2 M and 0 to 65 degrees C,
      respectively), high binding affinity (binding even in the absence of nonspecific
      DNA) with an apparent dissociation constant of approximately 3.7 x 10(-12) M, and
      high specificity (binding was unaffected in the presence of a 50,000 times excess
      of nonspecific DNA). From UV cross-linking and Southwestern analyses the
      molecular mass of PPBP was estimated to be approximately 30 kDa. PPBP is
      phosphorylated and may have a regulatory function because dephosphorylation
      abolished DNA binding activity. Differences in PPBP characteristics between
      nuclear extracts from Sf21 and from Bm5 (Bombyx mori) cell line suggested that
      additional factors may be involved in the interaction of PPBP with the polyhedrin
      promoter.

PMID- 8300609
TI  - Secretion-capture role for apolipoprotein E in remnant lipoprotein metabolism
      involving cell surface heparan sulfate proteoglycans.
AB  - To determine the impact of enhanced apolipoprotein (apo) E secretion on the
      mechanism of remnant lipoprotein uptake, rat hepatoma cells (McA-RH7777) were
      stably transfected with normal human apoE3 or receptor binding-defective apoE
      Leiden. After a 2-h incubation, the human apoE secreted from the transfected
      hepatocytes was 10-12 times greater than the endogenous rat apoE. The apoE3
      transfected cells bound and internalized rabbit beta-very low density
      lipoproteins (beta-VLDL) to a much greater degree than did apoE-Leiden
      transfected cells and nontransfected cells. The apoE3-secreting cells displayed a
      2-3.5-fold enhancement of cell-associated beta-VLDL compared to either the apoE
      Leiden-transfected or nontransfected cells. Fluorescently labeled beta-VLDL were
      observed to concentrate within intracellular granules of the apoE3-transfected
      cells, presumably within endosomes and lysosomes. Furthermore, electron
      microscopy revealed that the apoE3-secreting cells displayed abundant beta-VLDL
      and chylomicron remnants on their cell surfaces and microvilli, in contrast to
      non-transfected or apoE-Leiden-secreting cells. Electron microscopy also revealed
      an abundance of chylomicron remnants within intracellular vesicles and
      multivesicular bodies of apoE3-transfected hepatocytes. Heparinase treatment (3
      units/ml) completely abolished the increased association of beta-VLDL with apoE3
      transfected cells but did not affect the limited association of beta-VLDL with
      apoE-Leiden-transfected or nontransfected cells. We established that the apoE3
      enriched beta-VLDL were bound to cell surface heparan sulfate proteoglycans, as
      was the newly synthesized and secreted apoE3 (approximately 12% of the total
      secreted apoE3 was released by heparinase and suramin; 4% by heparin). In
      addition, reisolation of beta-VLDL by fast performance liquid chromatography
      after their incubation with exogenous apoE3, with medium from apoE3-secreting
      cells, or with the apoE3-secreting cells themselves revealed that the particles
      were enriched in apoE3 and displayed enhanced binding. These results suggest a
      secretion-capture role for apoE and indicate an important role for heparan
      sulfate proteoglycans on the cell surface for remnant lipoprotein metabolism.

PMID- 8300610
TI  - Zinc-free and reduced T4 gene 32 protein binds single-stranded DNA weakly and
      fails to stimulate UvsX-catalyzed homologous pairing.
AB  - The functional role of Zn(II) binding by T4 gene 32 protein (gp32), a single
      stranded DNA-binding protein, has been investigated by assessing the capacity of
      a well-characterized metal-free gp32 derivative to function in vitro as an
      accessory protein of T4 uvsX-catalyzed homologous pairing. Metal-free gp32 was
      prepared upon reaction of cysteine thiolates with methylmethanethiol-sulfonate to
      form the mixed disulfide Cys-SSCH3 or S-methylated species. Far and near
      ultraviolet circular dichroism spectroscopy suggest a moderate but easily
      detected change in the far UV region, accompanied by only a minor alteration in
      the near UV region, relative to the Zn(II)-containing protein. Restoration of the
      wild-type spectral features is accomplished upon the addition of 2 mM
      dithiothreitol and excess Zn(II) but not dithiothreitol alone. Unlike wild-type
      gp32, apo S-methylated gp32 shows weak binding to the recombination substrate,
      single-stranded M13mp19, and fails to stimulate homologous pairing with a linear
      M13mp19 duplex substrate by uvsX protein. Complete reactivation of the apo S
      methylated protein as a recombination-accessory protein is achievable in situ in
      the presence of reducing agent and sufficient exogenous Zn(II), but not one or
      the other alone. Analogous results are obtained with S-methylated C166S (Cys166-
      >Ser) gp32, revealing that only the metal-liganding cysteines participate in the
      reconstitution. These findings suggest that formation of the Zn(II) chelate is
      directly linked to single-stranded DNA binding and functional efficacy of gp32 in
      DNA metabolism.

PMID- 8300611
TI  - Concerted action of three distinct domains in the DNA cleaving-joining reaction
      catalyzed by relaxase (TraI) of conjugative plasmid RP4.
AB  - The TraI protein of plasmid RP4 (IncP alpha) catalyzes a site- and strand
      specific cleaving-joining reaction on form I or single-stranded DNA. Thus, TraI
      is one of the key components involved in the initiation and termination of
      horizontal DNA transfer by bacterial conjugation. Amino acid sequence comparison
      revealed three motifs in the TraI sequence conserved in relaxases from different
      origins. Site-directed mutagenesis of the traI structural gene and application of
      purified mutant TraI proteins for in vitro assays served to evaluate the
      functional importance of conserved amino acid residues. Two regions of TraI
      designated as motifs I and III are involved in catalyzing the cleaving-joining
      reaction. Motif I carries the tyrosine residue (Tyr-22), which covalently
      attaches TraI in a transesterification reaction to the 5' terminus of the cleaved
      DNA. Motif III contains one histidine residue (His-116) essential for relaxase
      activity and therefore proposed to activate the aromatic hydroxyl group of
      tyrosine 22 by proton abstraction. Exchange of a serine residue (Ser-74), located
      in motif II, against alanine prevents formation of stable relaxosomes but
      strongly enhances topoisomerase activity of the combination TraI/TraJ on form I
      oriT DNA. Motif II therefore might represent the DNA recognition domain of TraI.
      Our studies allowed us to establish a model of the interplay of three motifs
      located in the N-terminal region (amino acid positions 19-124) of TraI.

PMID- 8300612
TI  - Electrostatic modification at the amino termini of hemoglobin A.
AB  - The structural perturbations of the amino-terminal domains of hemoglobin A
      resulting from the carbamino adduct formation (a reversible in vivo electrostatic
      modification reaction) at Val-1(alpha) and Val-1(beta) is expected to be mimicked
      in the derivatives of HbA reductively alkylated at its alpha-amino terminus with
      aldehydes containing a negatively charged functional group at their distal end
      (double-headed reagents). Derivatives of HbA with galacturonic acid linked
      through alkylamino linkage either to Val-1(alpha) or Val-1(beta) (disubstituted
      derivatives) as well as to both Val-1(alpha) and Val-1(beta) (tetrasubstituted
      derivative) have been now prepared. All the three derivatives exhibit normal
      cooperativity but reduced O2 affinities. The functional consequence of the
      modification of HbA at its amino termini with D-galacuronic acid has been
      compared with that of the carboxymethylation of HbA at the same sites. This
      comparative study suggests that the stereochemistry of the carboxylate ion
      introduced into beta-cleft of Hb dictates the level of reduction in the O2
      affinity of the molecule seen on derivatization. However such a unique
      stereochemistry of the carboxylate ion of the reagent does not appear to be
      crucial to lower oxygen affinity when the modification is at the amino terminus
      of the alpha-chain. The molecular modeling studies demonstrate that the
      carboxylate ion of the carbamino adduct at the amino terminus of the beta-chain
      as well as the carboxylate of carboxymethyl group at the same site are in a
      geometrical orientation that favors the formation of an intrachain ionic
      interaction with the epsilon-amino group of Lys-82(beta). On the other hand the
      stereochemistry of a carboxylate ion of galacuronic acid on Val-1(beta) appears
      to be appropriate to form either an intrachian salt bridge with epsilon-amino
      group of Ly2-82(beta) of the same chain (intrachain) or alternatively an
      interchain salt bridge involving the epsilon-amino group of Lys-82(beta) of the
      trans chain. We speculate that the latter, i.e. trans configuration is favored as
      a result of the potential of D-galacturonic acid bound to Val-1(beta) to form an
      additional hydrogen bond with trans His-143(beta).

PMID- 8300613
TI  - Topology of an amiloride-binding protein.
AB  - Amiloride and structurally related compounds inhibit many transport proteins,
      enzymes, and drug or hormone receptors, although the topology of amiloride
      binding sites on these proteins has not been defined. We have previously raised
      and characterized a monoclonal antiamiloride antibody (mAb BA7.1) which is
      similar to epithelial Na+ channels in its specificity of binding of amiloride and
      amiloride analogs, suggesting that their amiloride binding sites may be similar
      in topology, mAb BA7.1 was used as a model system to analyze the three
      dimensional conformation of an amiloride binding site. The photoactive amiloride
      analog 2'-methoxy-5'-nitrobenzamil specifically labeled the heavy chain of mAb
      BA7.1, suggesting that the heavy chain participates in amiloride binding. The
      nucleotide sequences of the variable regions of the heavy and light chains of mAb
      BA7.1 were determined and amino acid sequences deduced to analyze the structure
      of the amiloride binding site. A comparative modeling approach was used to
      construct a model of the amiloride binding domain of mAb BA7.1, and a docking
      procedure was used to place amiloride within this domain. The model indicated
      that planar aromatic amino acid resides form a pocket into which amiloride, a
      planar molecule, inserts. Constraints on amiloride binding predicted by this
      model correlated with the measured specificity of binding of amiloride analogs
      with mAb BA7.1. These results provide a potential guide for the identification of
      motifs or amino acid contact residues present within other amiloride-sensitive
      proteins.

PMID- 8300614
TI  - Selective activation of phospholipase C by recombinant G-protein alpha- and beta
      gamma-subunits.
AB  - Receptor activation of phospholipase C (PLC) via G-proteins occurs by pertussis
      toxin-sensitive and toxin-insensitive signaling pathways. The alpha-subunits of
      the Gq family are presumed to mediate the toxin-insensitive pathway, but the
      nature of the G-proteins mediating the toxin-sensitive pathway is not
      established. Recently, PLC-beta has been shown to be activated by G-protein beta
      gamma-subunits of mixed or undefined composition. The relative activities of G
      protein subunits that might activate PLC-beta were examined using defined
      recombinant alpha- and beta gamma-subunits obtained from the baculovirus
      expression system by reconstituting the purified subunits with purified bovine
      brain PLC-beta 1 or turkey erythrocyte PLC-beta in unilamellar phospholipid
      vesicles. Turkey erythrocyte G alpha 11 and recombinant G alpha 11 and G alpha q
      obtained after expression in Sf9 cells activated both bovine brain PLC-beta 1 and
      turkey erythrocyte PLC-beta. In contrast, under the same assay conditions,
      recombinant G alpha i1, G alpha i2, G alpha i3, and G alpha o were without effect
      on either type of PLC. All types of beta gamma-subunits tested (r beta 1 gamma 2,
      r beta 1 gamma 3, r beta 2 gamma 2, r beta 2 gamma 3, bovine brain beta gamma or
      turkey erythrocyte beta gamma) inhibited G alpha 11-mediated activation of PLC,
      presumably by promotion of formation of inactive heterotrimeric G-protein. All
      types of beta gamma-subunits also markedly stimulated the activity of turkey
      erythrocyte PLC-beta but did not activate bovine brain PLC-beta 1. Of the four
      different beta gamma complexes of defined composition, three stimulated PLC with
      similar activities whereas beta 2 gamma 3 was less effective. The data suggest
      that pertussis toxin-sensitive activation of PLC is mediated by the beta gamma
      subunits of G-proteins acting on specific phospholipase C isoenzymes.

PMID- 8300615
TI  - Bile acid transport by the rat liver canalicular bile acid transport/ecto-ATPase
      protein is dependent on ATP but not on its own ecto-ATPase activity.
AB  - We have shown that bile acid efflux and ecto-ATPase activities are two distinct
      properties of a single rat liver hepatocyte canalicular membrane protein (Sippel,
      C. J., Suchy, F. J., Ananthanarayanan, M., and Perlmutter, D. H. (1993) J. Biol.
      Chem. 268, 2083-2091). Bile acid efflux in COS cells transfected with this rat
      hepatocyte canalicular bile acid transport/ectoATPase cDNA is stimulated by ATP
      and inhibited by nonhydrolyzable ATP analogs. In this study, we depleted
      transfected COS cells of ATP to examine whether bile acid efflux mediated by this
      transporter was dependent on ATP or just stimulated by ATP. We also used
      mutagenesis of an ATPase consensus sequence in the ectoplasmic domain to examine
      the relationship of ATPase activity to bile acid efflux mediated by the same
      polypeptide. The results indicate that bile acid transport is abrogated by ATP
      depletion and reconstituted by exogenous ATP in a concentration-dependent and
      saturable manner. Introduction of mutations at amino acids Gly97 and Arg98 in the
      ATPase consensus sequence abrogated ATPase activity but did not affect synthesis
      or cell surface delivery of the transporter and did not affect its bile acid
      transport activity. Taken together, the data indicate that bile acid efflux
      mediated by the rat hepatocyte canalicular bile acid transport/ecto-ATPase
      protein is dependent on ATP but not on its own ATPase activity. The data,
      therefore, imply that 1) ATP affects its bile acid transport activity through an
      entirely distinct mechanism; and 2) if there is any functional relationship
      between the ecto-ATPase and bile acid transport properties, it is mediated
      indirectly through regulation of net ATP concentrations in the canalicular space
      by the ecto-ATPase.

PMID- 8300616
TI  - Cloning and analysis of the C4 photosynthetic NAD-dependent malic enzyme of
      amaranth mitochondria.
AB  - In some C4 plant species, a mitochondrial NAD-dependent malic enzyme (EC
      1.1.1.39) (NAD-ME) catalyzes the decarboxylation of 4 carbon malate in the bundle
      sheath cells, releasing CO2 for the Calvin cycle of photosynthesis. In amaranth,
      a dicotyledonous NAD-ME-type C4 plant, the photosynthetic NAD-ME purified as two
      subunits of 65 and 60 kDa, designated alpha and beta, respectively. Antiserum
      raised against the alpha subunit reacted only with the 65-kDa protein in
      immunoblot analysis. Immunogold electron microscopy using the alpha subunit
      antiserum demonstrated that this protein was localized specifically to the
      mitochondrial matrix of bundle sheath cells. The complete nucleotide sequence of
      a 2300-base pair alpha subunit cDNA clone showed that this gene encodes a protein
      that contains all of the motifs required for a complete and functional malic
      enzyme. The alpha subunit has significant similarity along its entire length to
      other known NAD- and NADP-dependent malic enzymes from plants, animals, and
      bacteria. The findings presented here provide new insights about the C4
      photosynthetic NAD-ME and its evolutionary relationship to other forms of malic
      enzyme present in eukaryotic and prokaryotic organisms.

PMID- 8300617
TI  - Tumor necrosis factor induces a selective shedding of its p75 receptor from human
      neutrophils.
AB  - The effect of tumor necrosis factor alpha (TNF) on the expression of its specific
      receptors (p55 TNF-R and p75 TNF-R) on the surface of human neutrophils (PMN) and
      mononuclear cells (MNC) was investigated and compared to the effect of various
      agonists. PMN and MNC express both p55 and p75 TNF-R on their membranes. Within
      minutes of incubation with chemotactic factors or calcium ionophore A23187, both
      types of TNF-R were down-regulated from the surface on both cell populations. At
      the same time, soluble forms of these TNF-R appeared in supernatants, in amounts
      proportional to the extent of down-regulation induced by each stimulus,
      suggesting that shedding is the major mechanism leading to loss of p55 and p75
      TNF-R upon activation with these agonists. Likewise, TNF induced 60-80% and 73
      90% decreases in PMN surface p55 TNF-R and p75 TNF-R, respectively. However,
      modulation of the two types of TNF-R by TNF proceeded through different
      mechanisms. TNF induced a selective shedding of the p75 TNF-R since, by both
      enzyme-linked immunosorbent assay and Western blot analysis, only the p75 TNF-R
      was detected in supernatants of cells stimulated with TNF. Down-modulation of
      surface p55 TNF-R most probably resulted from TNF-induced receptor
      internalization, since 125I-TNF bound to PMN p55 TNF-R was rapidly internalized
      with a t1/2 = 5 min and preincubation of PMN with TNF inhibited by 68 +/- 6% the
      release of p55 TNF-R triggered upon subsequent treatment with A23187. The
      apparently unique property of TNF to induce a differential modulation of the two
      types of TNF-R at the surface of PMN and MNC might play an important role in the
      control of peripheral blood cell responses to TNF.

PMID- 8300618
TI  - Mechanism of cyclosporin A biosynthesis. Evidence for synthesis via a single
      linear undecapeptide precursor.
AB  - Cyclosporin A is synthesized by cyclosporin synthetase, a multienzyme
      polypeptide. This enzyme catalyzes at least 40 reaction steps in an assembly belt
      like mechanism. It activates all constituent amino acids of cyclosporin A to
      thioesters via amino acyladenylates and carries out specific N-methylation
      reactions. During elongation, the activated amino acids are linked by peptide
      bonds leading to enzyme-bound nascent peptide chains. Some of the linear peptides
      of the growing cyclosporin A chain were isolated and their N-terminal amino acid
      was determined. D-Alanine at position 8 of the cyclosporin A molecule was found
      to be a starting amino acid in the biosynthetic process of cyclosporin A
      formation. Four intermediate peptides of the growing peptide chain of cyclosporin
      A could be isolated and identified. All of them represent partial sequences of
      cyclosporin A starting with D-alanine. That these intermediate peptides were
      bound by thioester linkage to cyclosporin synthetase could be demonstrated by
      liberation of the peptides with performic acid. The peptides strongly suggest the
      stepwise synthesis of a single linear peptide precursor of cyclosporin A.

PMID- 8300619
TI  - Cloning and expression of the human gene for transaldolase. A novel highly
      repetitive element constitutes an integral part of the coding sequence.
AB  - A novel highly repetitive retrotransposable element was cloned based on a limited
      sequence homology to the human T-cell leukemia virus and a related endogenous
      retroviral sequence, HRES-1. This repetitive element was found to constitute an
      integral part of the coding sequence of the human gene for transaldolase. In
      comparison with the intronless yeast gene, structural analysis of the human
      transaldolase genomic locus revealed that the human gene is comprised of five
      exons, second and third of which uniquely developed by insertion of a
      retrotransposable element. The 1329-base pair full-length cDNA, clone 4/2-4/1,
      contains an open reading frame coding for a protein of 336 amino acids with a
      predicted molecular mass of 38 kDa. This protein shows a 58% overall sequence
      homology with the 37-kDa yeast transaldolase. Antibodies raised against a 22-kDa
      recombinant polypeptide expressed from a 474-base pair 5' fragment of clone 4/2
      4/1, containing repetitive exons 2 and 3, cross-reacted with yeast transaldolase
      and recognized the 38-kDa native human protein. Detection of a retrotransposon in
      the coding sequence of the human transaldolase gene demonstrates the importance
      of these repetitive elements in evolution of the eukaryotic genome.

PMID- 8300620
TI  - Carboxyl-terminal truncation impairs lipid recruitment by apolipoprotein B100 but
      does not affect secretion of the truncated apolipoprotein B-containing
      lipoproteins.
AB  - Human apolipoprotein (apo) B plays an obligatory role in the assembly and
      secretion of hepatic triglyceride-rich lipoproteins. Investigation of the
      truncated human apoB variants associated with hypobetalipoproteinemia has
      suggested that both size and secretion of apoB-containing lipoproteins may be
      reduced by carboxyl-terminal truncation. To examine the role of the carboxyl
      terminus of apoB in the assembly and secretion of hepatic lipoproteins, we have
      generated rat hepatoma McA-RH7777 cells that synthesize and secrete the full
      length human apoB100 and the truncated forms B94, B88, B80, B72, and B60. In the
      resulting lipoproteins, particle density was inversely related to the logarithm
      of apoB length, ranging from 1.019 g/ml for apoB100 to 1.06 g/ml for B60.
      Furthermore, particle diameter (as determined by non-denaturing gel
      electrophoresis) was directly correlated with apoB length, ranging from 21.4 nm
      for apoB100 to 17.7 nm for B60. The relationship between apoB length and particle
      geometry was best defined by a linear correlation between length and core volume;
      a 10% decrease in apoB length resulted in an approximately 13% decrease in core
      volume. These observations, which are in agreement with the observations of
      aberrant lipoproteins in hypobetalipoproteinemia, suggest that lipid recruitment
      by apoB is progressively reduced by carboxyl-terminal truncation. However, pulse
      chase studies indicated that carboxyl-terminal truncation did not impair apoB
      secretion. The recombinant human apoB forms were secreted as efficiently as
      endogenous rat apoB100; approximately 20% of total newly synthesized apoB72, B80,
      or B100 was secreted at the end of the chase. Intracellular degradation of newly
      synthesized apoB was observed for both the truncated human and the endogenous rat
      proteins. These data suggest that the low apoB levels in hypobetalipoproteinemia
      might not be caused by impaired secretion of the truncated apoB proteins.

PMID- 8300621
TI  - Acidic residues in extracellular loops of the human Y1 neuropeptide Y receptor
      are essential for ligand binding.
AB  - To investigate whether negatively charged residues of the human Y1 neuropeptide Y
      (NPY) receptor are required for ligand binding, a series of mutants were
      constructed in which aspartic acid and glutamic acid residues present in putative
      extracellular domains of the Y1 receptor were systematically replaced by
      alanines. The mutant cDNAs were transiently expressed in HeLa cells using a
      vaccinia virus-derived expression system, and their ability to bind NPY was
      evaluated. The level of expression of mutants unable to bind NPY was also tested
      immunologically. In addition, the ability of the mutant proteins to be recruited
      to the cell surface was assessed by confocal microscopy. Substitution of aspartic
      acids and glutamic acids of the N-terminal first extracellular domain had no
      effect on binding. On the other hand, substitution of acidic residues present in
      the second, third, and fourth extracellular loops resulted in proteins unable to
      bind 125I-NPY. These results demonstrate that the extracellular loops of the
      human Y1 NPY receptor are essential portions of its ligand binding domain.

PMID- 8300622
TI  - Association of utrophin and multiple dystrophin short forms with the mammalian
      M(r) 58,000 dystrophin-associated protein (syntrophin).
AB  - Electric tissue syntrophin, originally described as an M(r) 58,000 postsynaptic
      protein having homologs in mammalian muscle, was previously shown to associate
      with dystrophin in Triton extracts of Torpedo postsynaptic membranes. It also
      associates with the Torpedo M(r) 87,000 postsynaptic protein (87K), the core of
      which is a superdomain homologous to the cysteine-rich (CR) and COOH-terminal
      (CT) domains of human dystrophin. Using immunoaffinity purifications from various
      rat tissues and immunoblotting, we find that syntrophin associates with
      dystrophin, utrophin (the chromosome 6-encoded dystrophin homolog formerly known
      as dystrophin-related protein), multiple proteins which are cross-reactive with
      87K, and two subfamilies of 71K-like proteins (CRCT-containing proteins encoded
      by the dystrophin gene under the control of an alternative promoter in intron
      62). One 71K subfamily retains the dystrophin COOH-terminal sequence; the other
      has an alternative COOH-terminal sequence caused by deletion of the penultimate
      exon by alternative splicing. The relative masses of the members of the
      subfamilies suggest they arise by alternative splicing at other previously
      described sites within CT. These results establish that syntrophin is a general
      ligand for the CRCT domain in mammalian dystrophin and its homologs. They also
      reveal a greater diversity in 71K proteins than has previously been apparent.

PMID- 8300624
TI  - An Escherichia coli protein consisting of a domain homologous to FK506-binding
      proteins (FKBP) and a new metal binding motif.
AB  - Initially detected as a persistent contaminant in immobilized metal affinity
      chromatography of recombinant proteins in Escherichia coli, a 196-amino acid
      protein was isolated, cloned, overexpressed, and characterized. It consists of
      two domains, of which the first (146 amino acids) shows some homology to the
      FK506-binding proteins. The second domain (50 amino acids) is extremely rich in
      potentially metal-binding amino acids, such as histidine, cysteine, and acidic
      amino acids. The protein binds Ni2+ and Zn2+ tightly with 1:1 stoichiometry, Cu2+
      and Co2+ with lower affinity, and Mn2+, Fe2+, Fe3+, Mg2+, and Ca2+ hardly at all.

PMID- 8300623
TI  - Okadaic acid-dependent induction of the urokinase-type plasminogen activator gene
      associated with stabilization and autoregulation of c-Jun.
AB  - We have previously shown that the tumor promoter okadaic acid (OA), an inhibitor
      of protein phosphatases 1 and 2A, transcriptionally induces the urokinase-type
      plasminogen activator (uPA) gene in LLC-PK1 cells. This induction occurs
      independently of the protein kinase C- and cAMP-dependent signaling pathways.
      Here we show that a sequence located 2.0 kilobases upstream of the uPA gene,
      which resembles an AP-1-recognition sequence, mediates the action of OA. DNA
      protein interaction studies, together with mRNA and protein analyses, indicate
      that c-Jun, but not c-Fos, is involved in OA-dependent uPA gene induction. The
      appearance of high levels of uPA mRNA and DNA binding activity of c-Jun to the AP
      1-like site correspond to the appearance of c-Jun accumulation, suggesting that c
      Jun accumulation is a critical event in OA-dependent uPA gene induction. c-Jun
      protein levels increase significantly between 100 and 160 min following OA
      treatment, whereas c-Jun translation increases only slightly in this time frame,
      suggesting that post-translation mechanisms are also involved in c-Jun
      accumulation. Pulse-chase analyses shows that OA specifically stabilizes c-Jun.
      We discuss our results with respect to the possibility that protein phosphatase
      2A maintains c-Jun in its down-regulated state in LLC-PK1 cells.

PMID- 8300625
TI  - slyD, a host gene required for phi X174 lysis, is related to the FK506-binding
      protein family of peptidyl-prolyl cis-trans-isomerases.
AB  - Recessive mutations in the slyD gene were isolated by selecting for survival
      after induction of the cloned lysis gene E of bacteriophage phi X174 (Maratea,
      D., Young, K., and Young, R. (1985) Gene (Amst.) 40, 39-46). The slyD1 mutation,
      transduced into the normal phi X174 host, Escherichia coli C, confers an absolute
      block on the plaque-forming ability of the wild-type phage, indicating that slyD
      is required for E function rather than for expression from the plasmid vector.
      The cloning, sequencing, and deletion analysis of a 1-kilobase pair genomic
      fragment containing the slyD locus, mapping at 73.5', is reported. Three reading
      frames, orf72, orf159, and orf196, are contained within this fragment, with the
      latter two reading frames occupying the same DNA on opposite strands. Deletion
      analysis shows that the complementing activity is restricted to the orf159/orf196
      DNA. Complementation of the SlyD phenotype was observed irrespective of the
      orientation of the orf159/orf196 DNA with respect to a vector promoter,
      indicating that a cryptic promoter serves slyD on this fragment. Using site
      directed mutagenesis, nonsense mutations were created in each reading frame which
      were silent in the opposing frame. Both orf196 nonsense alleles failed to
      complement slyD1, whereas both orf159 nonsense alleles retained complementation,
      demonstrating rigorously that orf196 is slyD. A segment corresponding to the
      first 150 residues of the predicted SlyD protein has significant similarity
      throughout its length to the FKBP family of peptidyl-prolyl cis-trans-isomerases
      or rotamases. The COOH-terminal 46 codons of slyD encode a remarkable histidine
      rich peptide sequence which is at least partly dispensable for slyD function in E
      mediated lysis. Overexpression of slyD in E. coli is toxic. These findings are
      discussed in terms of a model for SlyD involvement in E function and in terms of
      a model for SlyD involvement of the ubiquitous FKBP rotamases.

PMID- 8300626
TI  - Sequence and function of the aas gene in Escherichia coli.
AB  - 2-Acylglycerophosphoethanolamine (2-acyl-GPE) acyltransferase and acyl-acyl
      carrier protein (acyl-ACP) synthase activities are encoded by the aas gene in
      Escherichia coli. The aas gene was cloned, and the DNA sequence of the aas gene
      and the region between aas and galR established the clockwise gene order in the
      61.2 min of the E. coli chromosome as aas-orf-galR-lysA-lysR-orf-araE. The aas
      gene consists of a single open reading frame of 2,157 base pairs predicted to
      encode a protein of 80.6 kDa. Strains harboring multiple copies of the aas gene
      overproduced both 2-acyl-GPE acyltransferase and acyl-ACP synthetase activities
      in vitro and had higher specific activities for the incorporation of exogenous
      fatty acids and lysophospholipids into the membrane in vivo. Specific expression
      of the aas gene yielded a protein with an apparent molecular mass of 81 kDa.
      Comparison of the predicted amino acid sequence of the aas gene with mammalian,
      yeast, and bacterial long chain acyl-coenzyme A synthetases revealed three
      domains of high similarity which are postulated to form the acyl-AMP binding
      pocket. These data verify that 2-acyl-GPE acyltransferase and acyl-ACP synthetase
      are reactions carried out by the same gene product, verify the role of 2-acyl-GPE
      acyltransferase/acyl-ACP synthetase in the acylation of endogenous 2-acyl-GPE,
      and establish the product of the aas gene as the rate-limiting enzyme in the
      uptake and incorporation of exogenous 2-acyllysophospholipids.

PMID- 8300627
TI  - A phorbol ester binding domain of protein kinase C gamma. High affinity binding
      to a glutathione-S-transferase/Cys2 fusion protein.
AB  - Cysteine-rich regions of protein kinase C (PKC) are implicated in diacylglycerol
      dependent regulation of kinase activity. The second cysteine-rich region
      (residues 92-173) of PKC gamma was expressed as a fusion protein with glutathione
      S-transferase in Escherichia coli and purified to homogeneity by affinity
      chromatography. This fusion protein displayed high affinity phorbol dibutyrate
      (PDBu) binding (Kd 23 nM). The phosphatidylserine dependence of PDBu binding was
      highly cooperative with Hill numbers (near 4.5) similar to those previously
      reported for PKC gamma (Burns, D. J., and Bell, R. M. (1991) J. Biol. Chem. 266,
      18330-18338). The fusion protein specifically bound 4 beta-hydroxy-PDBu but not
      the 4 alpha-stereoisomer. Furthermore, sn-1,2-dioctanoylglycerol (diC8)
      stereoselectively competed for PDBu binding. The cysteine-rich region was
      sufficient for association of the fusion protein to liposome preparations
      containing phosphatidylserine and phosphatidylcholine. Association was
      significantly enhanced in a stereospecific manner by the presence of PDBu as well
      as diC8. These results establish that a single cysteine-rich domain (residues 92
      173) of PKC gamma contains regions necessary and sufficient for lipid-dependent
      stereospecific interactions with PDBu and diC8. Furthermore, the region is
      sufficient to confer translocation of a fusion protein to liposomes in a PDBu-
      and diC8-dependent fashion. Thus, a single cysteine-rich region of PKC gamma
      displays many of the properties characteristic of PKC.

PMID- 8300628
TI  - A phorbol ester binding domain of protein kinase C gamma. Deletion analysis of
      the Cys2 domain defines a minimal 43-amino acid peptide.
AB  - Cysteine-rich regions of protein kinase C (PKC) are critical for the lipid
      dependent regulation of activity and are implicated in the coordination of zinc.
      A glutathione S-transferase fusion protein containing the second cysteine-rich
      region, Cys2, of PKC gamma with bound zinc with a stoichiometry of 1.8 +/- 0.1
      mol of zinc/mol of protein. Deletion analysis within this cysteine-rich region
      defined amino acids essential for zinc coordination. An NH2-terminal histidine
      (His102) and a COOH-terminal cysteine (Cys151) were both critical for the
      coordination of distinct zinc atoms. Both represent the ultimate residues of a 50
      amino acid consensus motif with six conserved cysteines and two conserved
      histidines present in the cysteine-rich regions of all PKC isoforms. Removal of
      histidine His102 abolished phorbol ester binding, while deletion of cysteine
      Cys151 did not. Deletion of valine (Val147) greatly diminished phorbol ester
      binding, which was completely lost only when valine (Val144) was also deleted. No
      significant further reduction in zinc stoichiometry below one resulted even when
      three COOH-terminal conserved cysteines (Cys151, Cys143, and Cys135) and a
      conserved histidine (His140) were deleted. These results are consistent with a
      model in which two zinc atoms are tetracoordinated per cysteine-rich region in
      two independent coordination spheres that are not functionally equivalent. These
      analyses determine a minimal peptide (residues 102-144) of 43 amino acids capable
      of [3H]PDBu binding.

PMID- 8300629
TI  - Highly potent transcriptional activation by 16-ene derivatives of 1,25
      dihydroxyvitamin D3. Lack of modulation by 9-cis-retinoic acid of response to
      1,25-dihydroxyvitamin D3 or its derivatives.
AB  - Although several studies have been performed on the biological activities of
      analogs of 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3) at the whole animal and
      cellular levels, little work has been done to analyze their transcriptional
      activation properties. A highly inducible 1,25-(OH)2 D3-responsive promoter
      composed of three copies of the mouse osteopontin vitamin D3 response element
      (VDRE3) inserted upstream of a herpes simplex virus thymidine kinase promoter has
      been constructed, and its transcriptional properties have been analyzed by
      transient transfection into the monkey kidney cell line COS-7 and the rat
      osteoblast-like osteosarcoma line ROS 17/2.8. We have studied systematically
      transcriptional activation by a number of 1,25-(OH)2 D3 analogs, particularly
      those substituted at positions 16, 23, 26, and 27, sites that are targets for
      metabolism. Strikingly, except for derivatives that bind the 1,25-(OH)2 D3
      receptor (VDR) very weakly, we find no parallel between the potency of action of
      a derivative as a transcriptional inducer and its affinity for the VDR.
      Derivatives substituted by multiple bonds at positions 16 and/or 23, although
      having varying affinities for the VDR, all stimulate transcription more potently
      than D3, in some cases at 100-fold lower concentrations. The peak transcriptional
      activity observed varies by only approximately 20% among different active
      analogs, indicating little difference in the activity of the VDR once bound to
      ligand. Gel retardation assays with ROS 17/2.8 nuclear extracts suggest that the
      VDR binds to the mouse osteopontin VDRE predominantly as a heterodimer with
      retinoid X receptor(s) (RXR(s)). We find that 9-cis-retinoic acid, the cognate
      ligand for RXRs, does not have a significant effect on the response of the VDRE3
      promoter to 1,25-(OH)2 D3 or a number of its derivatives in ROS 17/2.8 or in COS
      7 cells, under conditions in which promoters containing retinoid X response
      elements are activated. This suggests that 9-cis-retinoic acid may not act on the
      response to 1,25-(OH)2 D3 or its derivatives by directly influencing the
      transcriptional activity of VDR/RXR heterodimers. This promoter/reporter system
      should be useful for analyzing the tissue-specific transcriptional activity of
      1,25-(OH)2 D3 and its derivatives in any cell type amenable to transient
      transfection.

PMID- 8300630
TI  - Substitution at Pro385 of GLUT1 perturbs the glucose transport function by
      reducing conformational flexibility.
AB  - The mammalian glucose transporter, GLUT1, is capable of alternating between two
      conformations which expose either an outward- or inward-facing ligand binding
      site. The possibility that these conformational changes are related to the
      presence of prolines and glycines in transmembrane region 10 was investigated by
      site-directed mutagenesis. Chinese hamster ovary clones which were transfected
      with Pro385-->Ile and Pro385-->glycine mutations of GLUT1 were shown, by Western
      blotting and cell surface carbohydrate labelling, to have expression levels which
      were comparable with the wild type. The transport activity was markedly reduced
      as a result of the Pro385-->isoleucine but not in the Pro385-->glycine mutation.
      The loss of transport activity in the Pro385-->isoleucine clone was associated
      with loss of labeling by the exofacial photoaffinity ligand, 2-N-4-(1-azi-2,2,2
      trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2- propylamine (ATB-BMPA), but
      there was no loss in labeling by the inside site-directed ligand cytochalasin B.
      These results suggest that the transporter cannot adopt the outward-directed
      conformation in the Pro385-->isoleucine clone. By contrast, the glycine
      substitution for proline at this position resulted in a retention of the ligand
      binding properties at both inside and outside sites. We suggest a putative mode
      of operation of the transporter which involves conformational flexibility about
      the prolines in transmembrane segment 10 such that helices 11 and 12 can
      alternately either pack against the outside (ATB-BMPA binding) site in helices 7,
      8, and 9 or against the inner (cytochalasin B binding) site at the base of
      transmembrane segment 10.

PMID- 8300631
TI  - Comparison of myristoyl-CoA:protein N-myristoyltransferases from three pathogenic
      fungi: Cryptococcus neoformans, Histoplasma capsulatum, and Candida albicans.
AB  - Myristoyl-CoA:protein N-myristoyltransferase (Nmt) transfers myristate from CoA
      to the N-terminal Gly residue of cellular proteins in an ordered reaction
      mechanism that first involves binding of myristoyl-CoA to the apoenzyme. The gene
      encoding Saccharomyces cerevisiae Nmt1p (NMT1) is essential for vegetative
      growth. Candida albicans, Cryptococcus neoformans var. neoformans, and
      Histoplasma capsulatum are the principal causes of systemic fungal infections in
      immunocompromised humans. Metabolic labeling studies indicate that they
      synthesize a small set of cellular N-myristoylproteins during exponential growth
      on rich media, the most prominent of which co-migrate with two essential
      functionally interchangeable S. cerevisiae N-myristoylproteins, ADP ribosylation
      factor-1 (Arf1p) and Arf2p. NMT and ARF genes have been recovered from C.
      neoformans and H. capsulatum using the polymerase chain reaction. They are single
      copy genes, interrupted by multiple introns. C. neoformans and H. capsulatum Nmts
      have approximately 50% amino acid sequence identity with the orthologous S.
      cerevisiae, C. albicans, and Homo sapiens N-myristoyltransferases, whereas C.
      neoformans and H. capsulatum Arfs are approximately 80% identical with C.
      albicans Arf and S. cerevisiae Arf1p and Arf2p. Functional studies of C.
      neoformans and C. albicans Nmts conducted in Escherichia coli reveal that (i)
      both efficiently acylate S. cerevisiae Arf2p; (ii) C. neoformans Arf is a
      substrate for C. neoformans Nmt; and (iii) substitution of an Asp for a Gly
      located 5 residues from the C terminus of these two enzymes causes marked
      temperature-dependent reductions in their catalytic efficiency, just as it does
      with S. cerevisiae and H. sapiens Nmts. Wild type C. neoformans, C. albicans, and
      H. sapiens NMTs can fully complement the lethal phenotype of a S. cerevisiae nmt1
      null allele at 24 and 37 degrees C when the GAL1-10 promoter controlling their
      expression is induced by galactose. Only the C. albicans enzyme is able to do so
      when the promoter is repressed with glucose. This complementation profile likely
      arises, at least in part, from differences in the protein substrate specificities
      of the orthologous Nmts. A Gly-->Asp mutation in S. cerevisiae, C. neoformans, C.
      albicans, and H. sapiens Nmts produces temperature-sensitive growth arrest in
      isogenic S. cerevisiae strains with a nmt1 null allele. Growth of strains
      producing the mutant C. albicans or H. sapiens, but not the C. neoformans, enzyme
      can be rescued by myristate at the non-permissive temperature (37 degrees C) even
      in the presence of cerulenin, an inhibitor of fatty acid synthetase.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8300632
TI  - Endosomal proteolysis of insulin by an acidic thiol metalloprotease unrelated to
      insulin degrading enzyme.
AB  - Although insulin is degraded as a consequence of receptor-mediated endocytosis,
      the location and nature of the responsible proteinase(s) remain controversial.
      Insulin degrading enzyme (IDE; EC 3.4.22.11), a mainly cytosolic neutral thiol
      metalloendopeptidase of 110 kDa, has been proposed to be the main cellular
      clearance mechanism. However, endosomes concentrate and degrade internalized
      insulin demonstrating that IDE is unlikely to be the relevant enzyme for
      endosomal proteolysis of internalized insulin in liver parenchyma. In purified
      endosomal fractions insulin was actively degraded at acid pH and IDE was
      undetectable as evaluated by immunoblotting, immunoprecipitation, or chemical
      cross-linking procedures. Affinity purified endosomal acidic insulinase displayed
      a pH optimum of 4-5.5, a lack of inhibition by EDTA and N-ethylmaleimide, and a
      partial metal-ion requirement (for Mn2+) all of which distinguished it from IDE.
      A small but detectable presence of IDE in particulate nuclear (N) and large
      granule (ML) fractions was observed by differential centrifugation. By analytical
      centrifugation, IDE cosedimented with the organelle containing the peroxisomal
      marker proteins catalase and thiolase (median density, 1.21 g.cm-3). By
      preparative centrifugation, highly purified peroxisomes were observed to be
      enriched in IDE. Since all cloned cDNAs of IDE (human, rat, and Drosophila)
      reveal a deduced classical peroxisomal targeting sequence A/SKL at their carboxyl
      termini this may account for the peroxisomal location of IDE. Taken together, our
      studies identify an insulin-degrading enzyme in endosomes which is distinct from
      IDE. The latter's presence in peroxisomes suggests that its physiological
      substrate(s) in vivo are polypeptides other than insulin.

PMID- 8300633
TI  - Functional expression cloning of the canalicular sulfate transport system of rat
      hepatocytes.
AB  - We have cloned a single cDNA encoding the canalicular sulfate transporter of rat
      liver using Xenopus laevis oocytes as a functional expression system. The cloned
      cDNA sulfate anion transporter-1 (sat-1) expresses saturable Na(+)-independent
      sulfate uptake (Km approximately 0.14 mM) that can be inhibited by 4,4'
      diisothiocyano-2,2'-disulfonic acid stilbene (DIDS, IC50 = 28 microM) and
      oxalate, but not by succinate or cholate. These properties are very similar to
      sulfate uptake expressed in oocytes injected with total rat liver mRNA and to the
      bicarbonate/sulfate exchange system previously characterized in canalicular rat
      liver plasma membrane vesicles. The cloned sat-1 cDNA has a total length of 3726
      base pairs (bp) with an open reading frame encompassing 2109 bp, a 5'
      untranslated region of 367 bp, and a 3'-untranslated region of 1250 bp. The
      coding region predicts a protein of 703 amino acids with a calculated molecular
      mass of 75.4 kDa. Computer-based hydrophobicity analysis suggests the presence of
      12 putative transmembrane spanning domains. Furthermore, three potential
      glycosylation sites are detected (Asn-158, Asn-163, Asn-587). Northern blot
      analysis indicates that similar sulfate anion transporters are also present in
      the kidney, muscle, and brain of rat and in the liver of the mouse. Using
      antisense oligonucleotides the mRNA-species of the sat-1 analogue in rat kidney
      has been characterized by hybrid depletion experiments (Markovich, D., Bissig,
      M., Sorribas, V., Hagenbuch, B., Meier, P. J., and Murer, H. (1994) J. Biol.
      Chem. 269, 3022-3026).

PMID- 8300634
TI  - Expression of rat renal sulfate transport systems in Xenopus laevis oocytes.
      Functional characterization and molecular identification.
AB  - Renal proximal tubular sulfate reabsorption is mediated by brush border membrane
      Na+/sulfate-cotransport and basolateral Na(+)-independent sulfate transport.
      Injection of rat kidney cortex mRNA into Xenopus laevis oocytes induced Na(+)
      dependent as well as Na(+)-independent sulfate transport. The inhibition pattern
      of Na(+)-dependent uptake coincided with that known for the brush border
      membrane; the inhibition pattern of Na(+)-independent uptake suggested that this
      activity could be related to the basolateral cell surface. By Northern blot
      hybridization of size-fractionated mRNA, we provide evidence that the Na(+)
      dependent uptake is induced by an mRNA species related to a recently cloned cDNA
      encoding rat renal cortex Na+/SO4 cotransport (NaSi-1; Markovich, D., Forgo, J.,
      Stange, G., Biber, J., and Murer, H. (1993) Proc. Natl. Acad. Sci. U.S.A. 90,
      8073-8077); the Na(+)-independent sulfate transport activity seems to be related
      to an mRNA species encoding a rat liver Na(+)-independent sulfate transporter
      (Bissig, M., Hagenbuch, B., Stieger, B., Koller, T., and Meier, P. J. (1994) J.
      Biol. Chem. 269, 3017-3021). Hybrid depletion experiments using antisense
      oligonucleotides provided further evidence for the association of the expressed
      transport activities to NaSi-1 and sat-1, respectively.

PMID- 8300635
TI  - Functional comparisons between plant plasma membrane H(+)-ATPase isoforms
      expressed in yeast.
AB  - To examine the functional properties of the three major isoforms of plasma
      membrane H(+)-ATPase expressed in Arabidopsis thaliana (AHA1, AHA2, and AHA3), we
      employed a system for the heterologous expression of functional plant plasma
      membrane H(+)-ATPase in yeast (Villalba, J. M., Palmgren, M. G., Berberian, G.
      E., Ferguson, C., and Serrano, R. (1992) J. Biol. Chem. 267, 12341-12349). Each
      isoform was expressed efficiently but appeared to be retained in the endoplasmic
      reticulum of yeast. All isoforms displayed qualitatively similar enzymatic
      properties, but quantitative differences were found. When compared with AHA3,
      AHA1 and AHA2 had an apparent higher turnover rate for ATP hydrolysis, exhibited
      a 10-fold higher apparent affinity for ATP, and a 3-fold higher sensitivity
      toward vanadate. In addition, AHA2 had a slightly lower apparent affinity for H+
      and seemed to be more susceptible to activation by lysophosphatidylcholine than
      did AHA1 and AHA3. This study represents the first comparison of the functional
      properties of isoforms of the plant plasma membrane H(+)-ATPase.

PMID- 8300636
TI  - Transport and expression in human melanomas of a transferrin-like
      glycosylphosphatidylinositol-anchored protein.
AB  - Melanotransferrin, also called p97, is a cell surface glycoprotein which was
      first described as a marker antigen for human melanoma cells. Although p97 has a
      striking structural similarity to human serum transferrin and lactoferrin, its
      function has not yet been determined. One feature that distinguishes p97 from the
      other members of the transferrin family is the presence of a stretch of 24
      hydrophobic amino acids at the C terminus, previously assumed to form a
      proteinacious transmembrane domain. In this study, sensitivity to bacterial
      phosphatidylinositol-specific phospholipase C, biosynthetic labeling with
      [3H]ethanolamine, and partitioning in Triton X-114 are used to establish that p97
      is expressed at the cell surface as a glycosylphosphatidylinositol-anchored
      protein. In addition, to gain insight into the intracellular transport of p97,
      biosynthetic transport studies were performed on a melanoma cell line. These
      studies resulted in the identification of an additional form of p97 which is
      found in the medium and which likely does not originate from an alternatively
      spliced form of the p97 mRNA. These findings, together with our recent
      observation of the co-localization of p97 and the transferrin receptor in brain
      capillary endothelium (W. A. Jefferies, M. R. Food, R. Gabathuler, S.
      Rothenberger, T. Yamada, and P. L. McGeer, manuscript submitted) raise important
      questions about the function of the two forms of p97 detected and the possible
      involvement of this protein in a cellular iron uptake mechanism that is
      independent from the transferrin/transferrin receptor system.

PMID- 8300637
TI  - The primary and subunit structure of a novel type killer toxin produced by a
      halotolerant yeast, Pichia farinosa.
AB  - A halotolerant yeast, Pichia farinosa KK1 strain, produces a unique killer toxin
      termed SMK toxin (salt-mediated killer toxin) which shows its maximum killer
      activity in the presence of 2 M NaCl. The toxin consists of two distinct
      subunits, alpha and beta, which are tightly linked without a disulfide bond under
      acidic conditions, even in the presence of 6 M urea. Under neutral conditions,
      however, the alpha subunit precipitates, resulting in the dissociation of the
      subunits and the loss of killer activity. The nucleotide sequence of the SMK1
      gene predicts a 222 amino acid preprotoxin with a typical signal sequence, the
      hydrophobic alpha, an interstitial gamma polypeptide with a putative
      glycosylation site, and the hydrophilic beta. Amino acid sequence analyses of
      peptide fragments including the carboxyl-terminal peptides fragments including
      the carboxyl-terminal peptides from each subunit suggest that the alpha and beta
      subunits consist of amino acid residues 19-81 and 146-222 of the preprotoxin,
      respectively, and the molecular weight of the mature alpha beta dimer is 14,214.
      The KEX2-like endopeptidase and KEX1-like carboxypeptidase may be involved in the
      stepwise processing of the SMK preprotoxin. The maturation process and the
      functions of the SMK toxin are compared with the K1 toxin of Saccharomyces
      cerevisiae.

PMID- 8300638
TI  - Renaturation and tumor necrosis factor-alpha stimulation of a 97-kDa ceramide
      activated protein kinase.
AB  - Recent investigations identified a new signal transduction pathway, termed the
      sphingomyelin pathway, which may mediate the action of tumor necrosis factor
      (TNF) alpha and interleukin-1 beta (Mathias, S., Younes, A., Kan, C., Orlow, I.,
      Joseph, C., and Kolesnick, R. N. (1993) Science 259, 519-522). This pathway is
      initiated by hydrolysis of sphingomyelin to ceramide by a neutral
      sphingomyelinase and stimulation of a ceramide-activated Ser/Thr protein kinase.
      Recent investigations demonstrated that kinase activity is proline-directed,
      recognizing substrates in which the phosphoacceptor site is followed by a proline
      residue. Until now, the kinase has been defined only as a membrane-bound activity
      capable of phosphorylating a peptide derived from the sequence surrounding Thr669
      of the epidermal growth factor receptor. In the present studies, the kinase was
      quantitatively extracted from membrane with detergent and separated from protein
      kinase C by anion-exchange chromatography and isoelectric focusing. Ceramide
      activated protein kinase was resolved as an exclusively membrane-bound, 97-kDa
      protein with a pI of 7.05. Kinase activity toward the epidermal growth factor
      receptor peptide co-purified with activity toward a generic proline-directed
      substrate, myelin basic protein. Kinase activity was reconstituted by a
      denaturation-renaturation procedure and demonstrated activity toward self
      (autophosphorylation) and exogenous substrate (myelin basic protein).
      Autophosphorylation occurred exclusively on serine residues. These activities
      were enhanced to 7-fold of control by ceramide and TNF alpha. These
      investigations provide additional evidence for a role for ceramide-activated
      protein kinase in signal transduction for TNF alpha.

PMID- 8300639
TI  - Nucleotide dependence and cytoplasmic localization of a 49-kDa microtubule cross
      linking protein from the brine shrimp, Artemia.
AB  - Many different proteins associate with microtubules, influencing their spatial
      organization and function. These include proteins of a structural nature, which
      link microtubules to one another or to other cellular organelles and which may
      stimulate tubulin assembly. The second group, the so-called dynamic microtubule
      associated proteins, move subcellular components along microtubules through
      nucleotidase action. In this report the effects of nucleotides on a 49-kDa
      protein which appears to associate with ordered arrays of microtubules within
      Artemia are described, revealing a protein with novel characteristics. Efficient
      removal of the 49-kDa protein from microtubules assembled in cell-free extracts
      of Artemia occurred with GTP and some analogues of ATP, nonhydrolyzable or
      otherwise, but not with ATP itself. The latter nucleotide had a greater impact on
      cross-linking when microtubules were assembled from purified tubulin. The 49-kDa
      protein possessed a low level of nucleotidase activity, preferring either ATP or
      GTP as substrate. Unlike other microtubule-associated proteins, the enzymatic
      activity of the 49-kDa protein was not stimulated by microtubules, at least under
      assay conditions in which cross-linking was disrupted by nucleotides.
      Immunofluorescent staining of Artemia larvae by affinity-purified antibodies
      indicated that the 49-kDa protein is located in mitotic spindles, midbodies, and
      setal cells, all regions containing organized microtubules. The 49-kDa
      microtubule cross-linking protein from Artemia, through its unusual response to
      nucleotides and its cytoplasmic location, has a unique position within the
      heterogeneous family of microtubule-associated proteins described to date.

PMID- 8300640
TI  - Identification of tryptophan residues critical for the function and targeting of
      the gamma-aminobutyric acid transporter (subtype A).
AB  - The gamma-aminobutyric acid transporter is localized in nerve terminals. It
      catalyzes coupled electrogenic translocation of the neurotransmitter with two or
      three sodium ions and one chloride ion. The transporter contains 599 amino acids
      and 12 putative membrane spanning alpha-helices. It is the first described member
      of a neurotransmitter transporter superfamily. Using site-directed mutagenesis we
      have investigated the role of all 10 tryptophan residues predicted to reside in
      these helices. All 10 have been changed to serine as well as to leucine residues.
      Expression of mutant cDNAs in which the tryptophans, located in positions 68,
      222, and 230, are replaced by either of these two amino acids reveals that they
      are severely impaired in gamma-aminobutyric acid transport. Mutants in which a
      phenylalanine or a tyrosine residue is introduced, at either position 68 or 230,
      are active. On the other hand, at the 222 position replacement of the tryptophan
      by the aromatic amino acids results in inactive transport. After prelabeling of
      the proteins with [35S]methionine, immunoprecipitation of mutant transporters
      indicates that their expression levels are similar to those of the wild type.
      Reconstitution experiments, aimed to reveal the activity of transporter molecules
      not apparent in the plasma membrane, indicate that the lack of activity of the
      W230S transporter in intact cells is by and large due to its inefficient
      targeting to the plasma membrane. Tryptophan residues 68 and 222 appear to be
      required for the intrinsic activity of the transporter. Based on several
      observations, including one that tryptophan residue 222 is conserved in all amino
      acid transporter members of the superfamily, but not in those transporting
      biogenic amines, we hypothesize that the pi electrons of this tryptophan could be
      involved in the binding of the amino group of these neurotransmitters.

PMID- 8300641
TI  - A chimeric RecA protein exhibits altered double-stranded DNA binding.
AB  - RecAc38 protein, a chimeric RecA protein of Escherichia coli and Pseudomonas
      aeruginosa, is proficient in the renaturation from complementary single strands.
      However, RecAc38 protein showed a significant deficiency in promoting homologous
      pairing of single-stranded DNA and double-stranded DNA. RecAc38 protein was able
      to remove the secondary structure of single-stranded DNA, the first step of
      homologous pairing, at a slightly reduced rate. RecAc38 protein-single-stranded
      DNA-complex (presynaptic complex) was found to be deficient in the sequence
      independent binding to double-stranded DNA which is a step in the search for the
      homology. On the other hand, once unwinding was initiated, RecAc38 protein was
      able to propagate the unwinding of the double helix at the same extent as wild
      type RecA protein. These defects and the proficiency of RecAc38 protein are
      explained by a model showing that RecA protein has three distinct DNA strand
      binding sites (a site for the primary binding to single-stranded DNA, a site for
      the binding to a strand of second single- or double-stranded DNA, and a site
      required for the binding to the other strand of the double-stranded DNA) and that
      RecAc38 protein has a defect in the third site.

PMID- 8300642
TI  - Tissue-type plasminogen activator is a potent mitogen for human aortic smooth
      muscle cells.
AB  - Tissue-type plasminogen activator (t-PA) is a potent and efficacious mitogen for
      growth-arrested cultured human aortic smooth muscle cells, stimulating an
      increase in cell number at 0.3-30 nM concentration. Double-chain t-PA is as
      efficient as single-chain t-PA in stimulating smooth muscle cell mitogenesis,
      whereas single-chain urokinase-type plasminogen activator (u-PA) or u-PA and
      plasmin or plasminogen are ineffective. Plasminogen activator inhibitor-1,
      Pefabloc-TPA, diisopropyl fluorophosphate or alpha 1-anti-trypsin inhibit the
      mitogenic effect of t-PA for smooth muscle cells in a dose-dependent manner,
      showing that it is dependent on the enzymatic activity. t-PA activated
      phosphoinositide turnover in smooth muscle cells through a pertussis toxin
      insensitive pathway and stimulated proto-oncogene c-fos and c-jun mRNA levels.
      These findings indicate that t-PA stimulates vascular human smooth muscle cell
      proliferation and suggest for the first time that it may contribute to intimal
      smooth muscle cell proliferation after vascular injury as a result of angioplasty
      or vascular compromise during atherogenesis.

PMID- 8300643
TI  - Overexpression of hexokinase I but not GLUT1 glucose transporter alters
      concentration dependence of glucose-stimulated insulin secretion in pancreatic
      beta-cell line MIN6.
AB  - The recently established pancreatic beta-cell line MIN6 retains the ability to
      secrete insulin in response to physiological glucose concentrations. To
      investigate the role of glucose transport and phosphorylation in glucose
      stimulated insulin secretion by beta-cells, MIN6 cells were stably transfected
      with a rabbit GLUT1 glucose transporter cDNA or a rat hexokinase I cDNA cloned in
      an expression vector. Overexpression of GLUT1 increased 3-O-methylglucose uptake,
      but did not alter either glucose utilization or glucose-stimulated insulin
      secretion. In contrast, clones overexpressing hexokinase I exhibited enhanced
      glucose-stimulated insulin secretion at glucose concentrations below 10 mM with a
      concomitant increase in glucose utilization. Maximal insulin secretion as well as
      the maximal rate of glucose utilization were not altered in these clones. Insulin
      secretion stimulated by 2-ketoisocaproate, a non-glucose secretagogue, was not
      affected by hexokinase I expression. These results strongly suggest that the
      glucose phosphorylating step, but not glucose transport step, regulates glucose
      stimulated insulin secretion by modulating the glycolytic rate in the beta-cell.

PMID- 8300644
TI  - Single amino acid insertions probe the alpha subunit of the Escherichia coli F1F0
      ATP synthase.
AB  - Single amino acid insertions of alanine or aspartate have been introduced into
      the alpha subunit of the F1F0-ATP synthase at seven different sites, after
      residues 187, 193, 198, 202, 212, 217, and 222. These sites span a highly
      conserved region of the alpha subunit, parts of which are thought to be located
      in transmembrane spanning regions. Alanine insertions have little or no effect on
      function after positions 187, 193, 198, and 202, indicating that the region
      spanned by these residues is not essential for function. Alanine insertions after
      residues 212 and 217 disrupt ATP synthase function without grossly affecting the
      assembly of the enzyme, while the alanine insertion after residue 222 disrupts
      both ATP synthase function and assembly. All of the aspartate insertions are
      deleterious to ATP synthase function, except after residue 198. At the other six
      sites, aspartate insertions prevent growth on succinate minimal medium,
      indicating an inability to synthesize ATP. Aspartate insertions after residues
      187 and 193 result in alpha subunits that do not fractionate with membranes, as
      indicated by immunoblotting. These results support a model of the alpha subunit
      in which residues 187-193 and residues 212-222 are part of distinct transmembrane
      spans, separated by a short extramembrane loop. The results are consistent with
      an important interaction between residues 212-222 of the alpha subunit and b or c
      subunits. General aspects of "insertion scanning mutagenesis" are also discussed.

PMID- 8300645
TI  - Cloning and identification of testis-specific transcription elongation factor S
      II.
AB  - A new S-II cDNA clone was isolated from a rat testis library. This cDNA contained
      an open reading frame encoding 299 amino acid residues. The deduced amino- and
      carboxyl-terminal regions were very similar with those of Ehrlich cell S-II,
      which we reported previously, but the sequence of the intervening 46 amino acid
      residues was unique. This new S-II was expressed in the testis but not in the
      other rat tissues examined, suggesting that it was a testis-specific S-II.
      Recombinant testis-specific S-II produced in Escherichia coli was shown to
      stimulate RNA polymerase II.

PMID- 8300646
TI  - Characterization of the human A1 adenosine receptor gene. Evidence for
      alternative splicing.
AB  - To approach transcriptional and translational regulation of adenosine receptors,
      we have isolated cDNA and genomic clones of the human A1 adenosine receptor
      (A1AR). The cDNA, when inserted into the pCMV5 expression vector and transfected
      into COS-7 or CHO cells, leads to the expression of a functional A1AR that
      displayed all the appropriate pharmacologic properties. The human A1AR gene
      consists of at least six exons and five introns. A single intron interrupts the
      coding sequence, while the remaining introns are within the 5'-untranslated
      region. Comparison of our cDNA with one by Libert et al. (Libert, F., Van Sande,
      J., Lefort, A., Czernilofsky, A., Dumont, J. E., Vasart, G., Ensinger, H. A., and
      Mendla, K. D. (1992) Biochem. Biophys. Res. Commun. 187, 919-926) reveals that
      exon 4 in the 5'-untranslated region was completely missing from their sequence.
      Study of mRNAs from a range of human tissues by reverse transcription-polymerase
      chain reaction using a variety of primers revealed clear evidence for alternative
      splicing. Transcripts containing exons 4, 5, and 6 were found in all tissues
      expressing A1AR, while a separate transcript with exons 3, 5, and 6 was seen only
      in selected tissues. No transcript contains both exons 3 and 4. No evidence for
      expression of exons 1 and 2 could be discerned. Exon 4 contains two AUG
      initiation codons with reasonable Kozak consensus, suggesting the possibility of
      translational regulation. Exon 3 contains no AUG initiation codons.

PMID- 8300647
TI  - Non-amyloidogenic cleavage of the beta-amyloid precursor protein by an integral
      membrane metalloendopeptidase.
AB  - The beta-amyloid precursor protein (beta-APP) is a membrane spanning
      glycoprotein. The small beta-protein domain within the precursor is presumed to
      be the source of amyloid found in plaques characteristic of Alzheimer's disease.
      The amino terminus of beta-APP is released from cells by cleavages that produce
      both potentially amyloidogenic and nonamyloidogenic fragments of the carboxyl
      terminus. We developed a cell free system that imposes specificity and co
      localization to characterize the proteolytic activity that cleaves the precursor
      within the beta-protein domain. A reporter protein containing the carboxyl
      terminal 105 amino acids of beta-APP provided a specific substrate for cleavage
      at Lys16 of the beta-protein. The protease inhibitor profile and solubility
      characteristics of the activity demonstrate the cleavage is produced by an
      integral membrane metalloendopeptidase.

PMID- 8300648
TI  - Regulation of phospholipase A2 activity in undifferentiated and neutrophil-like
      HL60 cells. Linkage between impaired responses to agonists and absence of protein
      kinase C-dependent phosphorylation of cytosolic phospholipase A2.
AB  - We compared the regulation of cytosolic phospholipase A2 (cPLA2) activity in
      undifferentiated and neutrophil-like HL60 cells. Although Ca(2+)-mobilizing P2
      purinergic receptors are expressed in both cell types, arachidonic acid (AA)
      release stimulated by P2-purinergic agonists was 5-7-fold higher in the
      differentiated cells. Similarly, the stimulation of AA release by AlF4- in intact
      cells or by ATP and guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) in
      electropermeabilized cells was significantly higher in the differentiated cells.
      Treatment with phorbol 12-myristate 13-acetate (PMA) enhanced A23187-stimulated
      AA release in intact HL60 granulocytes with minimal effects in the
      undifferentiated cells. Immunoblotting experiments showed similar levels of cPLA2
      and of agonist-mediated activation of mitogen-activated protein kinase in both
      cell types. Experiments measuring stimulation of AA release by either melittin,
      using endogenously labeled intact cells, or Ca2+, using homogenates and exogenous
      substrate, indicated that undifferentiated cells do not lack an activatable PLA2.
      The stimulatory effects of GTP gamma S and Ca2+ on AA release in homogenates from
      endogenously labeled cells suggested that undifferentiated cells display G
      protein-cPLA2 coupling. Basal and PMA-stimulated phosphorylation of cPLA2 was
      detected in differentiated, but not in undifferentiated cells. However, the two
      cell types displayed only subtle differences in the time courses of
      phosphorylation of mitogen-activated protein kinase triggered by agonists and
      PMA. The observed defect in cPLA2 phosphorylation may represent the alteration
      preventing agonist-mediated stimulation of AA release in undifferentiated HL60
      cells.

PMID- 8300649
TI  - Making do without randomised trials.

PMID- 8300650
TI  - The straight cervical spine: does it indicate muscle spasm?
AB  - The loss of cervical lordosis in radiographs of patients presenting with neck
      pain is sometimes ascribed to muscle spasm. We performed a cross-sectional study
      of the prevalence of 'straight' cervical spines in three populations: 83 patients
      presenting to an accident department with acute neck pain, 83 referred to a
      radiology department with chronic neck problems, and 80 radiographs from a normal
      population survey carried out in 1958. Curvature was assessed on lateral
      radiographs both subjectively and by measurement. The prevalence of 'straight'
      cervical spines was 19% in the acute cases and 26% in the chronic cases. The 95%
      confidence interval for the difference was -6.4% to +19.3%. In the normal
      population 42% showed a straight spine, but a further third of these films had
      been taken in a position of cervical kyphosis; this probably reflects a
      difference in positioning technique. Women were more likely than men to have a
      straight cervical spine, with an odds ratio of 2.81 (95% CI 1.23 to 6.44). Our
      results fail to support the hypothesis that loss of cervical lordosis reflects
      muscle spasm caused by pain in the neck.

PMID- 8300651
TI  - Ligamentotaxis with an internal spinal fixator for thoracolumbar fractures.
AB  - We assessed narrowing of the spinal canal in 39 burst fractures and fracture
      dislocations of thoracolumbar vertebrae treated by the AO Internal Spinal
      Fixator, using CT preoperatively and at various stages postoperatively. Computer
      aided planimetry was used to measure the narrowing, and its restoration shortly
      after instrumentation, or at 15 months. The mean initial reduction of canal area
      was to 63.7% +/- 18.8% of normal; this was restored to a mean of 95.4% +/- 21.2%
      of normal when measured either soon after surgery or at 15 months (p < 0.001 for
      both groups). There was more improvement in cases assessed later. For fractures
      from D12 to L3, the mean canal area was restored to 99.4% of normal; but at L4 or
      L5 the mean restitution was to only 60.9% (p < 0.05). We found no correlation
      between preoperative loss of area and amount of restoration, or severity of
      neurological deficit. Nor was there any correlation between the delay before
      surgery and the improvement achieved. The mechanism of fracture reduction appears
      to be a combination of distraction ligamentotaxis and forced hyperextension.

PMID- 8300652
TI  - Cystic tuberculosis of bone in children.
AB  - We treated 13 children with histologically confirmed cystic tuberculosis of bone.
      Ten had solitary cystic lesions and three had the multicystic form. Signs and
      symptoms were related mainly to the joint adjacent to the cyst. Most lesions were
      in the metaphyses of long bones. They were radiolucent, round or oval, and
      resembled pyogenic infections, aneurysmal and simple bone cysts, cartilaginous
      tumours or osteoid osteoma. Only two of the children had pulmonary tuberculosis.
      The Mantoux skin test was negative in four children and the ESR was normal in
      five. Curettage followed by anti-tuberculosis therapy for one year resulted in
      good healing, but two children had residual joint contractures. Biopsy should be
      taken from the cystic area rather than from the synovium when a joint is
      involved.

PMID- 8300653
TI  - Voluntary subluxation of the shoulder in children. A long-term follow-up study of
      36 shoulders.
AB  - We reviewed 25 children who presented consecutively with voluntary (habitual)
      subluxation of the shoulder. Thirty-six shoulders were involved and symptoms had
      been present for an average period of 12 years. Eighteen children were managed by
      'skillful neglect': all these had become fully active in the profession of their
      choice and were satisfied with the outcome. Two of them had required shoulder
      surgery in adult life but only after trauma. Seven children (ten shoulders) had
      undergone stabilising operations during childhood with the aim of preventing
      later degenerative arthritis. These patients were also active in their selected
      professions, but only three (five of the ten shoulders) had good results: two
      shoulders had recurrent instability, two were painful and one was stiff. None of
      the shoulders in either group had developed osteoarthritic changes. There was no
      association with emotional or psychiatric problems. We conclude that voluntary
      subluxation of the shoulder in children has a favourable prognosis and that there
      is no indication for surgical intervention during childhood.

PMID- 8300654
TI  - The use of a hydroxyapatite block for innominate osteotomy.
AB  - We used hydroxyapatite blocks to keep open Salter innominate osteotomies in 19
      children (21 hips), avoiding the need for an autograft taken from the anterior
      superior iliac spine. Our results were satisfactory, with less deformation of the
      iliac bone, and a reduction of both blood loss and operating time.

PMID- 8300655
TI  - Removal of metaphyseal bone tumours with preservation of the epiphysis. Physeal
      distraction before excision.
AB  - In immature long bones, radical excision of malignant tumours of the metaphysis
      may necessitate sacrifice of the adjacent epiphysis. To preserve the adjacent
      joint while allowing a safe margin of excision, we used physeal distraction
      before removing the tumour. From July 1984 to August 1992, we operated on 20
      patients by this method. After a mean follow-up of 54 months there was no local
      recurrence in the epiphyseal region. Three patients had developed pulmonary
      metastases.

PMID- 8300656
TI  - Treatment of grade-IIIb open tibial fractures. A prospective randomised
      comparison of external fixation and non-reamed locked nailing.
AB  - Severe open fractures of the tibia have a high incidence of complications and a
      poor outcome. The most usual method of stabilisation is by external fixation, but
      the advent of small diameter locking intramedullary nails has introduced a new
      option. We report the early results of a randomised, prospective study comparing
      external fixation with non-reamed locked nails in grade-IIIb open tibial
      fractures. Of 29 patients, 15 were treated by nails and 14 by external fixation.
      Both groups had the same initial management, soft-tissue procedures, and early
      bone grafting. All 29 fractures healed within nine months, but the nailed group
      had slightly better motion and less final angulation. Complications included one
      deep infection and two pin-track infections in the external fixator group and one
      deep infection and one vascular problem in the nailed group. Although the
      differences in healing and range of motion were not statistically significant, we
      found that the nailed fractures were consistently easier to manage, especially in
      terms of soft-tissue procedures and bone grafting. It is the treatment preferred
      by patients and does not require the same high level of patient compliance as
      external fixation. The only factors against nailing are the longer operating time
      and the greater need for fluoroscopy. We consider that locked non-reamed nailing
      is the treatment of choice for grade-IIIb open tibial fractures.

PMID- 8300657
TI  - Simultaneous calcaneocuboid and talonavicular fusion. Long-term follow-up study.
AB  - We examined 16 feet, 33 to 133 months (mean 83) after simultaneous calcaneocuboid
      and talonavicular fusions performed for a variety of painful disorders of the
      hindfoot. Objectively, four feet were rated excellent, eight good, four fair and
      none poor. There was one asymptomatic nonunion of the talonavicular joint.
      Progressive degenerative arthritis of the ankle was seen in six patients and of
      the naviculocuneiform joint in seven. Biomechanically, simultaneous
      calcaneocuboid and talonavicular arthrodesis is better than an isolated
      talonavicular fusion and is a simple and effective alternative to triple
      arthrodesis.

PMID- 8300658
TI  - Fungal osteomyelitis of the foot. A report of an unusual case.
AB  - Mucormycosis is an opportunistic infection that very occasionally causes
      osteomyelitis and avascular necrosis of bone. The infection may prove fatal if
      not diagnosed promptly. If early treatment is instituted the prognosis is good.

PMID- 8300659
TI  - The heel pad in plantar heel pain.
AB  - A study of heel-pad thickness and compressibility using lateral radiographs,
      loaded and unloaded by body-weight, was carried out on 70 patients with plantar
      heel pain and 200 normal subjects. The heel-pad thickness and the compressibility
      index (resistance to compression) were greater in the patients than in normal
      subjects and significantly increased with age. In normal subjects, the thickness
      was greater in males than in females, but there was no significant difference in
      the compressibility. Increased weight led to an increase in heel-pad thickness
      and compressibility index. The body mass index was greater in patients with
      plantar heel pain than in normal subjects and 40% of the patients were considered
      to be overweight. Increase in the compressibility index indicates loss of
      elasticity and an increased tendency to develop plantar heel pain.

PMID- 8300660
TI  - Muscle function after mid-shaft femoral shortening. A prospective study with a
      two-year follow-up.
AB  - We performed isokinetic knee testing to assess thigh muscle function in ten
      patients (12 legs) before and after mid-shaft femoral shortening averaging 46 mm
      (27 to 70). Tests were at angular velocities of 60 degrees/sec and 180
      degrees/sec, and were performed preoperatively and after 3, 6, 12 and 24 months.
      Isokinetic tests at two years showed a significant reduction in muscle function
      in both quadriceps and hamstrings, but recovery of function was significantly
      better for the hamstrings. There was a linear relationship with correlation of r2
      = 0.31 to 0.86 between loss of muscle force at two years and the magnitude of
      shortening. Long-term loss of muscle force should be expected after a mid-shaft
      shortening of the femur of more than 10%.

PMID- 8300661
TI  - The anatomy of the palmar scaphotriquetral ligament.
AB  - The palmar ligaments of the wrist were dissected in 15 adult cadaver wrists and
      demonstrated by MRI in three. Ten fetal wrists (10 to 19 weeks' gestation) were
      studied in histological sections. The palmar scaphotriquetral ligament was found
      in them all. Its attachment to the triquetrum is substantial but that to the
      scaphoid is thin and fan-shaped, its fibres interdigitating with those of the
      radioscaphocapitate ligament. The contribution of the ligament to carpal
      stability has yet to be studied, but it may help to support the head of the
      capitate when the wrist is dorsiflexed.

PMID- 8300662
TI  - Osteotomy for deformity of the radius. Computer-assisted three-dimensional
      modelling.
AB  - A computer-assisted method of preoperative planning was used to create virtual
      models of the deformed distal end of the radius after malunion of a fracture. By
      comparison with a similar model of the uninjured wrist, values were calculated
      for the angles and lengths to be corrected by osteotomy. Shifts of the distal
      fragment were analysed for 33 deformed wrists, 27 of which underwent corrective
      osteotomy and bone grafting. In more than half the cases there was dorsal or
      volar shift of 3 mm or more. The accuracy of the correction was measured by
      comparing the three-dimensional models before and after osteotomy with the model
      of the normal wrist. The volar and ulnar inclination angles of the articular
      surface of the radius and the radial length were regularly restored to normal.

PMID- 8300663
TI  - Neurological deterioration after cement injection into a vertebral body.

PMID- 8300664
TI  - Weight-bearing parallel-beam scanography for the measurement of leg length and
      joint alignment.

PMID- 8300665
TI  - Tibial stress fractures in two professional golfers.

PMID- 8300666
TI  - Comparison of MRI with bone scanning for suspected hip fracture in elderly
      patients.

PMID- 8300667
TI  - Posterior reattachment of the torn anterior cruciate ligament.

PMID- 8300668
TI  - Bone regrowth after laminectomy.

PMID- 8300669
TI  - Fractures of the calcaneum.

PMID- 8300671
TI  - Ultrasound diagnosis of CDH.

PMID- 8300670
TI  - Ultrasound diagnosis of CDH.

PMID- 8300672
TI  - Knee replacement in haemophilia.

PMID- 8300673
TI  - Bone surface preparation.

PMID- 8300674
TI  - Youth is a risk factor for stress fracture. A study of 783 infantry recruits.
AB  - We report a prospective study of 783 male Israeli recruits aged from 17 to 26
      years. The risk of stress fracture was inversely proportional to age on both
      univariate and multivariate analysis. Each year of increase of age above 17 years
      reduced the risk of stress fracture by 28%.

PMID- 8300675
TI  - Locked intramedullary nailing of humeral shaft fractures. Implant design,
      surgical technique, and clinical results.
AB  - We report our experience with a modified implant and a new technique for locked
      intramedullary nailing of the humerus in 41 patients. Locking was by cross-screws
      placed from lateral to medial in the proximal humerus, and anteroposteriorly in
      the distal humerus. Early in the series, 11 nails were inserted at the shoulder,
      but we found that rehabilitation was faster after retrograde nailing through the
      olecranon fossa, which was used for the other 30. We used a closed technique for
      29 of the nailings. Of the 41 patients treated, 21 had acute fractures, five had
      nonunion, and 15 had pathological fractures. Secure fixation was obtained for
      comminuted and osteoporotic fractures in any part of the humeral shaft, which
      allowed the early use of crutches and walking frames. Two nails were locked at
      only one end, and one of these became the only failure of union after an acute
      fracture.

PMID- 8300676
TI  - Organising the management of life-threatening injuries.

PMID- 8300677
TI  - Iatrogenic displacement of fracture-dislocations of the shoulder. A report of
      seven cases.
AB  - We report seven cases in which open or closed reduction of a shoulder dislocation
      associated with a fracture of the humeral neck led to displacement of the neck
      fracture. Avascular necrosis of the humeral head developed in all six patients
      with anatomical neck fractures. All five anterior dislocations also had a
      fracture of the greater tuberosity and both posterior dislocations had a fracture
      of the lesser tuberosity. The neck fracture had not initially been recognised in
      three of the seven cases. In five cases attempted shoulder reduction led to
      complete displacement of the head segment, which was treated by open reduction
      and minimal internal fixation. In the other two cases, shoulder reduction caused
      only mild to moderate displacement which was accepted and the fracture was
      treated conservatively. We conclude that biplane radiography is essential before
      reduction of a shoulder dislocation. Neck fractures must always be ruled out,
      especially where there are tuberosity fractures. In our series, careful closed
      reduction under general anaesthesia with optimal relaxation and fluoroscopic
      control did not prevent iatrogenic displacement. Prophylactic stabilisation of
      the neck fracture should be considered before reduction of such a fracture
      dislocation. It may be, however, that the prevention of displacement by
      prophylactic stabilisation does not always prevent late avascular necrosis; we
      observed this in one case.

PMID- 8300678
TI  - Long-term results of revision hip arthroplasty. Survival analysis with special
      reference to the femoral component.
AB  - We report a clinical and radiological survival analysis of 148 consecutive
      revisions of hip arthroplasties. All patients referred were offered revision if
      it was indicated and they were medically fit. About one-third (32%) had had at
      least one previous revision, and about one-third had an established deep
      infection. The revisions were performed in ultra-clean air with body-exhaust
      suits. The usual method of fixation was by contained and pressurised cement of
      standard viscosity, to which appropriate antibiotics had been added in infected
      cases. Some patients had cementless revision. Clinical failure meant that one or
      both of the implants had been removed; radiological failure was assessed from
      serial radiographs. The clinical survival at ten years was 95%. The Merle
      D'Aubigne and Postel rating for pain improved from a mean of 2.9 to 5.2; and in
      Charnley group A and B cases, walking ability improved from 2.3 to 4.3. In
      contrast to some reports we also found good radiological survival; this was 90.5%
      for cemented femoral stems. Isoelastic revision stems inserted without cement
      gave poor results.

PMID- 8300679
TI  - Cemented revision for femoral osteolysis in cemented arthroplasties. Results in
      29 hips after a mean 8.5-year follow-up.
AB  - We reviewed 29 consecutive patients after cemented femoral revision of cemented
      hip arthroplasties for osteolysis. After an average follow-up of 8.5 years,
      osteolysis had recurred in only two cases (6.9%) and 25 femoral components (86%)
      remained well fixed.

PMID- 8300680
TI  - Causes of dislocation of total hip arthroplasty. CT study of component alignment.
AB  - We reviewed radiographs and CT scans of 38 total hip arthroplasties which had
      dislocated (36 posteriorly; 2 anteriorly) and compared the alignment of the
      prosthetic components with those of 14 uncomplicated arthroplasties. No
      difference was found between the alignment of the prosthetic components in the
      two groups. In the seven patients who had reoperations, the cause of dislocation
      diagnosed by CT was confirmed in only two cases (one retroversion of the cup and
      one protruding osteophyte). Muscular imbalance rather than malposition of the
      components was the major factor determining dislocation. CT allows accurate
      measurement of cup and neck anteversion but contributes little to preoperative
      planning.

PMID- 8300681
TI  - Failure of the cement-bone interface. A consequence of strengthening the cement
      prosthesis interface?
AB  - We report the early failure, at a mean of 37 months, of 17 femoral prostheses due
      to aseptic loosening at the cement-bone interface. In every case the prosthesis
      had been manufactured with a surface coating designed to enhance the strength of
      the cement-prosthesis interface. It is postulated that improving the bond at the
      cement-prosthesis interface may transfer increased stress to the cement-bone
      interface and cause early failure at that interface.

PMID- 8300682
TI  - Long-term results of uncemented alumina acetabular implants.
AB  - We report the clinical and tribological performance of 67 ceramic acetabular
      prostheses implanted between 1976 and 1979 without bone cement. They articulated
      with ceramic femoral heads mounted on mental femoral stems. After a mean elapsed
      period of 144 months, 59 sockets were radiographically stable but two showed
      early signs and six showed late signs of loosening. Four of the loose sockets
      have been revised. Histological analysis of the retrieved tissue showed a fibrous
      membrane around all the implants, with fibrocartilage in some. There was no bone
      ingrowth, and the fibrous membrane was up to 6 mm thick and infiltrated with
      lymphocytes, plasma cells, and macrophages. Intra- and extracellular birefringent
      wear particles were seen. Tribological analysis showed total wear rates in two
      retrieved alumina-on-alumina joints of 2.6 microns per year in a stable implant
      and 68 microns in a loose implant. Survival analysis showed a revision rate of
      12.4% at 136 months.

PMID- 8300683
TI  - Isolated traumatic dislocation of the hip. Long-term results in 50 patients.
AB  - From 1974 to 1989, we treated 50 patients with a simple dislocation of the hip:
      38 were posterior dislocations and 12 were anterior. All dislocations primarily
      treated at our hospital were reduced by closed methods within three hours (mean
      85 minutes (10 to 180)) and 43 were reviewed after an average follow-up of 8
      years (2 to 17). It is widely held that isolated hip dislocation reduced within
      six hours gives an excellent outcome, but we found a significant number of
      complications. There were radiological signs of partial avascular necrosis in
      two, mild osteoarthritis in seven, and moderate degeneration in two. Heterotopic
      ossification was seen in four patients, but 29 of 33 MRI examinations were
      normal. Objective evaluation according to the Thompson and Epstein (1951)
      criteria showed fair and poor results in 3 of 12 anterior dislocations, but in 16
      of 30 posterior dislocations. In six of the seven patients with no other severe
      injury, the hip had an excellent or good result; in only three of the eight
      patients with severe multiple injuries was this the case. The important factors
      in the long-term prognosis appear to be the direction of the dislocation and the
      overall severity of injuries.

PMID- 8300684
TI  - Composition and morphology of wear debris in failed uncemented total hip
      replacement.
AB  - Interfacial membranes collected at revision from 11 failed uncemented Ti-alloy
      total hip replacements were examined. Particles in the membranes were
      characterised by electron microscopy, microchemical spectroscopy and particle
      size analysis. Most were polyethylene and had a mean size of 0.53 micron +/- 0.3.
      They were similar to the particles seen in the base resin used in the manufacture
      of the acetabular implants. Relatively few titanium particles were seen.
      Fragments of bone, stainless steel and silicate were found in small amounts. Most
      of the polyethylene particles were too small to be seen by light microscopy.
      Electron microscopy and spectroscopic techniques are required to provide an
      accurate description of this debris.

PMID- 8300685
TI  - Corrosion and wear at the modular interface of uncemented femoral stems.
AB  - We examined 108 uncemented femoral stems with modular femoral heads which had
      been retrieved for reasons other than loosening. There were detectable amounts of
      wear and corrosion in 10 of 29 (34.5%) mixed-alloy components and 7 of 79 (9%)
      single-alloy components after a mean implantation time of 25 months. We found no
      correlation between the presence or extent of corrosion or surface damage and any
      of time in situ, initial diagnosis, reason for removal, age, or weight. Stems
      with wear and corrosion were less likely to show histological bony ingrowth. The
      interface between the head and stem of modular total hip components is a possible
      source of ion release and wear debris, but wear and corrosion were totally absent
      in most specimens. This suggests that this problem could be avoided, and that
      further research is required to develop manufacturing methods which would
      minimise such changes.

PMID- 8300686
TI  - Surface damage to cobalt-chrome femoral head prostheses.
AB  - Fifty-four cobalt-chrome alloy femoral heads were retrieved at revision surgery
      or at post-mortem; 23 came from uncemented, eight from hybrid and 23 from
      cemented hip arthroplasties. The uncemented and hybrid implants had porous
      coating, metal backing and modular femoral heads; with one exception none of the
      cemented implants had any of these. Twenty-five of the 31 heads from uncemented
      and hybrid arthroplasties, and 11 of the 23 heads from cemented arthroplasties
      showed surface damage involving more than 25% of the surface. Scanning electron
      microscopy revealed multidirectional fine scratches 1 micron to 10 microns in
      depth and width which appeared to have been made by fine, hard particles. There
      was a higher rate of such damage in the uncemented and hybrid arthroplasties than
      in the cemented implants, suggesting that the abrasive particles were mainly
      released from the metal, rather than from the cement or polyethylene components
      of the implants.

PMID- 8300687
TI  - Inflammatory arthritis after failure of silicone rubber replacement of the radial
      head.
AB  - The management of radial head fractures complicated by ligamentous disruption
      remains a matter of controversy. The use of a silicone radial head implant to
      provide temporary stability is thought to help to protect the ligaments during
      healing. The reported complications of long-term implantation of a silicone
      replacement include fracture, dislocation, synovitis, lymphadenitis and
      subchondral resorption. We now report one case in which an inflammatory process
      resulted in generalised cartilage degeneration. This has not previously been
      noted.

PMID- 8300688
TI  - Over-the-top or tunnel reconstruction of the anterior cruciate ligament? A
      prospective randomised study of 54 patients.
AB  - We report a review of 54 patients with chronic anterior cruciate ligament rupture
      treated by patellar-quadriceps tendon graft augmented with polypropylene braid
      (Kennedy-LAD). The femoral placement of the graft was randomised to either a
      modified over-the-top (OTT) or a tunnel position obtained by an isometric drill
      guide (ISO). At the two-year follow-up both procedures had resulted in
      improvement of subjective knee function and activity level. Stereoradiographic
      measurements showed reduction of anteroposterior laxity to near normal in about
      one-third of the patients, but muscle strength and objective functional
      performance showed little or no changes. The OTT group had better subjective knee
      function. We were unable to confirm the theoretical advantages of the use of the
      drill guide, partly because it provided a tibial tunnel which was too anterior.

PMID- 8300689
TI  - Soft-tissue expansion before total knee arthroplasty in arthrodesed joints. A
      report of two cases.
AB  - We report two cases in which arthrodesed knees were revised to total
      arthroplasties after the use of soft-tissue expanders. Case 1 had had multiple
      operations on her knee and had been arthrodesed for septic arthritis two years
      earlier. Case 2 had had knee arthrodesis for severe osteoarthritis 18 years
      before revision. In both patients, tissue expanders were used to increase the
      soft tissues available for cover and to help to mobilise the extensor mechanism.
      The operations were made much easier, and in both patients a range of motion from
      0 degrees to 90 degrees was achieved at operation.

PMID- 8300690
TI  - Spinal deformity after childhood surgery for tuberculosis of the spine. A
      comparison of radical surgery and debridement.
AB  - We have reviewed 80 children who were involved in the Medical Research Council
      (UK) trial of surgical treatment for tuberculosis of the spine in Hong Kong.
      Radical surgery or debridement had been performed at mean ages of 7.6 years (n =
      47) and 5.1 years (n = 33) respectively. The patients were followed up to
      skeletal maturity (mean 17 years). Spinal deformity was measured on lateral
      radiographs taken preoperatively, at six months, one year, five years and at
      final follow-up. Radical surgery and grafting produced a reduction in kyphos and
      deformity angles at six months; this correction was maintained during the growth
      period. By contrast, after debridement surgery there was an increase in deformity
      at six months, with a tendency to some spontaneous correction during the growth
      period. There were statistically significant differences between angles for the
      radical and debridement groups only at six months postoperatively, but the
      changes during later follow-up were similar in the radical and debridement
      groups. Our findings highlight the importance of the surgical correction of
      deformity, and provide no evidence to suggest that disproportionate posterior
      spinal growth contributes to progression of deformity after anterior spinal
      fusion in children.

PMID- 8300691
TI  - Perioperative prophylactic cephazolin in spinal surgery. A double-blind placebo
      controlled trial.
AB  - We investigated the efficacy of a single dose of 1 g of cephazolin in reducing
      postoperative infections in patients undergoing 'clean' operations on the lumbar
      spine. In a double-blind, randomised, trial there were 21 wound or urinary
      infections in the 71 patients who received placebo and nine in the 70 who
      received cephazolin (p < 0.05). Nine of the placebo patients (12.7%) developed
      wound infections (complicated by bacteraemia in two) compared with three (4.3%)
      in the cephazolin group (p = 0.07). Hospital stay was longer for infected
      patients than for non-infected patients (p < 0.05). Cephazolin-resistant
      pathogens were isolated more frequently from patients who received cephazolin
      than from those who received placebo.

PMID- 8300692
TI  - Burn patients: coming of age? The 1993 Presidential Address to the American Burn
      Association.

PMID- 8300693
TI  - Burn care in Africa: reducing the misery index: the 1993 Everett Idris Evans
      Memorial Lecture.
AB  - Burn care in Africa is hampered by inadequate facilities, inadequate
      infrastructure, and inadequately trained staff. Burn units with burn teams are
      few. Burn injuries carry a high mortality rate with delayed healing and high
      complication rates among survivors. Most burns occur in the home from flame and
      scalding, and children are more affected than adults. Burn sepsis is mostly from
      staphylococci and pseudomonas. Various studies on epidemiology, sepsis, protein
      metabolism, and repigmentation indicate methods of prevention and improved care,
      including greater resort by surgeons to skin grafting, which speeds healing and
      both prevents and treats scarring, contractures, and depigmentation. Governments,
      industries, and entrepreneurs are exhorted to promote burn prevention, research,
      improved care, and rehabilitation, particularly through the establishment of burn
      units with burn teams, to reduce the misery and suffering caused by the high
      mortality and morbidity from burns in Africa.

PMID- 8300694
TI  - Acetylcholine receptor subunit mRNA changes in burns are different from those
      seen after denervation: the 1993 Lindberg Award.
AB  - Neuromuscular dysfunction of burn trauma is evidenced as muscle weakness and
      altered sensitivity to neuromuscular relaxants. A biochemical characteristic of
      the neuromuscular dysfunction is the proliferation and spread of acetylcholine
      receptors (AChR) throughout the skeletal muscle membrane. Depending on whether
      the neuromuscular dysfunction is presynaptic, synaptic, or postsynaptic in
      origin, the transcripts that induce the proliferation of AChR differ. This study,
      by quantitation of mRNA transcripts of AChR in muscle, attempts to characterize
      the cause of the neuromuscular dysfunction of burn trauma. Examination of the
      levels of mRNA encoding alpha, beta, epsilon, gamma, and delta subunits of AChR
      with northern blot analysis indicate significant (p < 0.03) elevations of beta
      subunit mRNA with a trend for increased levels of alpha and delta transcripts. An
      increase of gamma-subunit mRNA, typical of presynaptic or nerve-mediated
      neuromuscular dysfunction, was not observed after burns. That neuronal
      (presynaptic) factors do not cause the neuromuscular dysfunction was confirmed by
      the lack of elevation of transcripts of myoD and myogenin, which also increase in
      "denervation states." These findings indicate that the neuromuscular dysfunction
      of burn trauma is most likely related to synaptic or postsynaptic factors.
      Further characterization of the cause of the synaptic and postsynaptic
      neuromuscular changes in burns will have implications for the choice of
      therapeutic agents to rectify the neuromuscular dysfunction.

PMID- 8300695
TI  - Free radical activity and loss of plasma antioxidants, vitamin E, and sulfhydryl
      groups in patients with burns: the 1993 Moyer Award.
AB  - This study examines the relationship of burn injury and plasma levels of
      conjugated dienes, total sulfhydryl groups, and vitamin E in patients with
      thermal injuries. Plasma neopterin levels were determined as an index of
      macrophage activity and serine elastase as an index of polymorphonuclear cell
      activation. Thirteen patients with burns, six survivors and seven nonsurvivors,
      were studied for the first 4 days, then every other day until postburn day 14.
      Twelve healthy volunteers served as the control group. Survivors had 56% +/- 4%
      total body surface area burned, and nonsurvivors had 63.9% +/- % total body
      surface area burned. The patients with burns, compared with the control group,
      showed elevated plasma levels of the lipid peroxidation products conjugated
      dienes (0.767 +/- 0.045 vs 0.269 +/- 0.013 Abs at 233 nm) and reduced levels of
      the natural scavengers of free radicals, vitamin E (196.2 +/- 12.6 vs 841.1 +/-
      22.7 micrograms/dl) and total sulfhydryl groups (54.0 +/- 0.4 vs 15.8 +/- 1.0
      mumol/dl). The total sulfhydryl groups/conjugated dienes ratio fell at a greater
      rate (9.8% +/- 3.2% vs 3.2% +/- 0.7%/day) in nonsurvivors than in survivors (p <
      0.05 by Mann-Whitney). The levels of elastase were slightly elevated in the
      patients with burns, but there was no difference between survivors and
      nonsurvivors. Normal neopterin levels are 3 to 10 nm/L; peak levels were 119 +/-
      48 nm/L in nonsurvivors and 37.4 +/- 10 nm/L in survivors. Patients with burns
      demonstrated evidence of increased oxygen free radical activity and activation of
      polymorphonuclear cell and macrophages. Nonsurvivors demonstrated increased
      consumption of antioxidants compared with survivors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8300696
TI  - Thermal injury-associated neopterin production: regulation by interleukin-2.
AB  - Pteridin neopterin production by monocytes/macrophages has been linked to the
      biologic activity of immune activation- and/or infection-related cytokines. In
      patients with thermal injuries who succumb to infections, serum levels of both
      interleukin-2 (IL-2) and neopterin are significantly increased. However, the
      relationship between these two markers of immune activation remains unclear. This
      study examines the role of IL-2 in the biosynthesis of neopterin after major
      burn. Up to 4 weeks after burn, the levels of plasma neopterin and endotoxin were
      elevated in all patients studied (N = 9, 30% to > 90% total body surface area).
      Intact (unsupplemented) peripheral blood mononuclear cell (PBMC) cultures from
      patients with sepsis secreted high levels of neopterin spontaneously. The
      spontaneous release of neopterin was significantly decreased (p < 0.05) after
      supplementation with exogenous IL-2. The reverse was observed in peripheral blood
      mononuclear cell cultures from infection-free or control groups where relatively
      low neopterin secretion was markedly augmented in the presence of IL-2. The
      effect of IL-2 in patient cultures was unrelated to the activity of endogenous
      interferon gamma, because the production of this cytokine was profoundly reduced.
      However, IL-2-induced alterations in neopterin secretion paralleled those in the
      production of tumor necrosis factor alpha. This suggests that after thermal
      injury, biologic responses of neopterin-secreting peripheral blood mononuclear
      cells are directly or indirectly regulated by IL-2.

PMID- 8300697
TI  - The effects of high-dose vitamin C therapy on postburn lipid peroxidation.
AB  - The effects of vitamin C treatment (14 mg/kg/hr) on postburn lipid peroxidation
      were evaluated in 12 dogs. A lymph duct above the ankle was cannulated
      bilaterally. Hourly lymph flow rates, plasma and lymph total protein
      concentrations, and plasma and lymph malondialdehyde concentrations were measured
      before the burn injury and for 24 hours after the burn injury. Four groups were
      employed: nonburn without treatment, nonburn with vitamin C treatment, burn
      without treatment, and burn with vitamin C treatment. The nonburn groups showed
      no significant differences in lymph flow rates, total protein flux, or lymph
      malondialdehyde level. In the burn groups the postburn hourly lymph flow rate
      increased by 850% without treatment and by 500% with vitamin C treatment, whereas
      the postburn hourly total protein flux increased by fiftyfold and twentyfold,
      respectively. There was a significant reduction in the postburn lymph
      malondialdehyde level in the group treated with vitamin C as compared with the
      nontreatment group. We conclude that high-dose vitamin C administration
      diminishes early postburn lipid peroxidation and reduces microvascular leakage of
      fluid and protein.

PMID- 8300698
TI  - Effects of propranolol administration on cardiac responses to burn injury.
AB  - Previous studies showing that propranolol upregulates beta-adrenergic receptors
      and protects against myocardial ischemia led us to hypothesize that preburn
      propranolol would protect against postburn cardiac dysfunction. Guinea pigs were
      treated with propranolol 3 mg/kg/day for 14 days, then deeply anesthetized and
      subjected to a 45% 3 degrees scald burn; eight guinea pigs treated with
      propranolol served as the control group (group 1). Burned guinea pigs were
      resuscitated with Ringer's lactate given as either 4 ml (group 2, N = 8), 6 ml
      (group 3, N = 10), or 8 ml (group 4, N = 6) per kg/% burn. Guinea pigs treated
      for 14 days with vehicle (water) were subjected to either sham burn (non
      propranolol control, group 5, N = 10) or burn and treatment (group 6, N = 10) as
      described for group 2. Fluid resuscitation in non-propranolol-treated guinea pigs
      failed to overcome burn-induced cardiac deficits, as indicated by significantly
      lower left ventricular pressure, 86 +/- 2 versus 62 +/- 3 mm Hg; +dP/dt max, 1365
      +/- 43 versus 1110 +/- 44 mm Hg/sec; -dP/dt max, 1184 +/- 31 versus 881 +/- 40 mm
      Hg/sec, p < 0.001. Burn-mediated cardiac defects occurred in all propranolol
      treated guinea pigs regardless of the fluid volume given. Our data show that (1)
      propranolol did not protect against burn-induced cardiac dysfunction, and (2)
      chronic beta-adrenergic blockade increases postburn fluid requirements for
      maintenance of cardiodynamic stability and for survival.

PMID- 8300699
TI  - Dysfunctional metabolism induced by the systemic effects of burn trauma: the role
      of rates of polyinositol and glycerophosphate formation in diaphragm.
AB  - Common complications among patients with burns are respiratory problems.
      Inspiration for breathing normally is facilitated by diaphragmatic contractility.
      However, in burn trauma numerous factors impose on skeletal muscle activity and
      chest wall function. These present limitations to surgical procedures requiring
      anesthesia. The hypothesis of this study was that the systemic effects of
      increasing burn size may result in metabolic changes in the polyinositol part of
      the phosphatidyl inositol signal transduction system in diaphragm. In this
      report, rate changes in polyinositol phosphates (i.e., inositol triphosphate
      (IP3), inositol 1,4 biphosphate (I1,4P2), inositol 1 phosphate (I1P), and
      inositol) that occurred in diaphragm subjected to the systemic effects of burn
      trauma were examined. Third-degree burn injury was applied by scalding predefined
      areas (i.e., 0%, 20%, and 50% body surface area) on the dorsal and ventral
      surfaces of mice. At postburn day 21 tissues were harvested and the levels of the
      polyinositol phosphates were measured by incorporation of myo-[2-3H]-inositol
      with separation of the phosphates by anion-exchange chromatography. All actual
      levels and rates of formation were analyzed with standard statistical tests and
      curve-fitting routines. Rate changes of the labelled [3H]-polyinositol phosphates
      were determined for the control, 20%, and 50% groups. These data show that rate
      changes occur in the polyinositol part of the phosphatidyl signal transduction
      system and are caused by the systemic effects of large percent body surface area
      burns. The changes that occur in the polyinositol phosphates provide insight into
      dysfunctional processes that can affect skeletal muscle physiology. The long-term
      goal of these studies is that they will lead to therapeutic advancements in the
      treatment of respiratory dysfunction in patients with burns.

PMID- 8300700
TI  - Acceleration of skin regeneration from cultured epithelial autografts by
      transplantation to homograft dermis.
AB  - Cultured epithelial autografts transplanted to homograft dermis were analyzed
      histopathologically from 9 days to 2.25 years after grafting and compared with
      cultured epithelial autografts transplanted to wound beds devoid of homograft
      dermis in the same patient. The results suggested that grafting to a dermal
      substrate accelerates biologic events in skin regeneration from cultured
      epithelial autografts. Both rete ridge development and normalization of the
      epidermal keratin program from a "hyperproliferative" to a normal pattern
      occurred months sooner in the cultured epithelial autografts placed on a dermal
      matrix. Regeneration of anchoring fibrils was also accelerated. Neither
      repopulation by Langerhans cells nor repigmentation appeared to be altered
      significantly by grafting to dermal tissue. By special stain, the elastin network
      of the allograft dermis could still be visualized at 2.25 years, indicating long
      term persistence of the homograft matrix. By clinical assessment the rate of
      successful engraftment ("take rate") of cultured epithelial autografts grafted to
      allodermis was estimated to be about 95%, and long-term durability was excellent.

PMID- 8300701
TI  - Alteration in gastrointestinal peptides after thermal injury in humans.
AB  - Alterations in gastrointestinal function are common after thermal injury in
      humans. The peptide hormones gastrin and cholecystokinin are known to exert
      effects on gastric and biliary motility and on secretory function and to induce
      trophic changes in gut mucosa. The effect of injury on these hormones has
      received little attention. Six patients with burns were studied while receiving a
      combination of regular diet and continuous enteral feeding. Four healthy members
      of the nursing staff served as the control group. Blood was drawn every 4 hours
      for 24 hours. Gastrin and cholecystokinin were analyzed by radioimmunoassay.
      Patients with burns demonstrated significantly higher levels of gastrin and lower
      levels of cholecystokinin when compared with the control group. Patients with
      burns also failed to demonstrate the normal circadian variation in these
      peptides.

PMID- 8300702
TI  - The pharmacokinetics of ibuprofen after burn injury.
AB  - Ibuprofen is an effective antipyretic in the postburn period and produces
      associated decrements in the hypermetabolic response. Burn injury is capable of
      altering the kinetics of many drugs, making the predictable use of agents such as
      ibuprofen difficult. Ten patients with serious burns were studied after the
      administration of 10 mg/kg ibuprofen suspension. The half-life varied from 1.4 to
      5.1 hours, depending on the site of administration and/or the presence of solid
      food. The reported half-life for ibuprofen suspension is 1.8 to 2 hours. Burn
      size did not alter ibuprofen half-life or area under the time-concentration
      curve. Maximum ibuprofen concentration varied greatly, depending on route of
      administration. Time to maximal temperature reduction was between 2 and 3 hours
      after drug administration. Although the precise level of ibuprofen needed for
      cyclooxygenase inhibition is unknown, enteral administration results in levels
      below the targeted 10 to 20 mcg/ml for much of the traditional 6-hour dosing
      interval. Future studies with ibuprofen in the burn population must standardize
      more than just total dose.

PMID- 8300703
TI  - Guinea pigs with large burns are consistently hypermetabolic without an
      associated increment in rectal temperature.
AB  - This study was conducted to examine the guinea pig as a suitable model for the
      study of the postburn hypermetabolic response and the febrile response that
      accompanies burn injury in man. Thirty animals were randomly assigned to four
      groups: > 50% body surface area burn (n = 6); 45% to 50% body surface area burn
      (n = 10); < 45% body surface area burn (n = 6); and controls (n = 8). On postburn
      days 3, 7, 11, 13, and 15, sequential temperature measurements were made. On
      postburn days 7 to 15, the randomly selected burn group (n = 12) and the control
      group (n = 8) had calorimetry studies performed. Sequential rectal temperature
      data demonstrate that the guinea pig does not mount a prolonged or consistent
      febrile response after burn injury (p > 0.05 for burn group vs control group on
      postburn days 7 to 13; p < 0.05 for postburn days 3 and 15 only). However, the
      burned guinea pig is significantly hypermetabolic after burn injury, with
      significant increases in dry and evaporative heat loss. The hypermetabolic
      response was proportional to burn wound size. Guinea pigs are not an ideal model
      for the study of the postburn febrile response; however, this is an excellent
      model for the study of postburn hypermetabolism.

PMID- 8300704
TI  - Psychosocial sequelae of pediatric burns involving 80% or greater total body
      surface area.
AB  - Important questions for pediatric burn care specialists relate to the quality of
      life for those children who survive the most severe burn injuries. This study
      examines the psychological adjustment of 25 children who survived injuries > or =
      80% total body surface area and the impact of such injury on the families. Data
      were analyzed from the most recent assessment, with the Child Behavior Checklist,
      Teacher Report Form, Piers-Harris Children's Self-Concept Scale, Parenting Stress
      Index, and a parental questionnaire designed by the authors. As a group, the
      children's behavioral problems as reported by both parents and teachers were
      within normal limits. Measures of parental stress, however, clearly
      differentiated the burn population. These parents attributed more stress to
      characteristics of their children. Children with > or = 80% TBSA burns develop
      positive feelings about themselves and appear no more troubled than a comparable
      group of nonburned children. The impact on the families is significant, however,
      and must be considered of consequence in the rehabilitation of the burned child.

PMID- 8300706
TI  - Hope for healing hidden wounds.

PMID- 8300705
TI  - A comparison of the Tanner and Bioplasty skin mesher systems for maximal skin
      graft expansion.
AB  - Maximizing wound coverage of patients with burns who have meshed autografts is a
      primary intervention for wound closure. This study compared the Tanner and
      Bioplasty skin graft meshing systems for optimal skin graft expansion. Twenty
      patients for skin grafting were randomly assigned to either a Tanner or Bioplasty
      skin mesher group. Skin expansion ratios used with the Tanner group were 1.5:1
      and 3:1, while Bioplasty ratios included 2:1 and 4:1. The patients' thighs were
      used exclusively as donor sites, and all grafts were harvested by the same
      surgeon. Expanded skin ratios were compared as to the difference in percent of
      predicted expansion outcome compared with the actual areas of the measured skin
      grafts. Comparing the differences of actual skin expansion with expected
      expansion, statistically significant results were found. When meshed skin grafts
      are used for wound closure, a 12.9% to 58.6% greater than anticipated area of
      donor skin should be harvested based on the expansion ratio selected.

PMID- 8300707
TI  - Trans-osseous ilio-femoral by-pass. A new extra-anatomical by-pass.
AB  - A new extra-anatomical by-pass is described as an alternative procedure to solve
      complicated vascular problems in the groin. This trans-osseous ilio-femoral by
      pass can be use in spite of classical extra-anatomical by-passes (obturator,
      perineal, supra-pubic, axillo-femoral). The proximal anastomosis can be performed
      on aorto-iliac homolateral axis by a retro-peritoneal approach. The by-pass is
      going externally on the psoas-iliac muscle, through the iliac aisle and then
      between the sartorius and gluteus medius muscle. Distal anastomosis can be
      performed on the profunda femoral artery or, with sequential by-pass, on multiple
      arteries of the leg. We have performed such a by-pass in 5 patients for femoral
      triangle infection (4 cases) or radiotherapeutic complication. One patient died
      after cardiac surgery, another has had a major amputation. Three by-passes are
      patent with a follow-up period of 2 years. This by-pass is easy to do, its route
      is short, deep (without neurological, bleeding or compressive risk) and far from
      an eventual infected common femoral artery.

PMID- 8300708
TI  - Progression of carotid atherosclerosis. Three year follow-up and analysis of risk
      factors.
AB  - OBJECTIVE: To elicit the risk factors associated with increasing grades of
      stenosis in patients with carotid plaque. STUDY DESIGN: Retrospective review of
      serial duplex scans of the carotid bifurcation. Case note review for documented
      risk factors. SETTING: Irvine Laboratory of the Academic Department of Surgery,
      Vascular Section. PATIENTS AND RESULTS: Review of serial duplex scans of the
      carotid bifurcation was performed on 200 unselected patients who each had a
      follow-up of at least three years. Definite progression of carotid
      atherosclerosis was defined as an unequivocal increase in at least one grade by
      the criteria of Strandness, and was documented in 50 patients (25%). Even if the
      initial situation is normal or minimal disease (< 15% stenosis), once definite
      plaque progression is observed, the lesion will progress to a hemodynamically
      significant one (> 50%) in 67% of this patient population. The only risk factor
      for plaque progression that we defined is hypertension, and this may be spurious.
      There are no risk factors associated with the subgroup of plaques that progress
      rapidly above those that progress at a slower rate. CONCLUSIONS: There are no
      risk factors defined in this population which are associated with advancing
      carotid atherosclerosis.

PMID- 8300709
TI  - Fibromuscular dysplasia of the internal carotid artery: long-term surgical
      results.
AB  - Fifty-eight patients underwent 72 operations for symptomatic fibromuscular
      dysplasia (FMD) between 1970 and 1986. There were 35 females and 23 males aged
      between 36 and 76 years (average 56). Among the 72 operated on lesions (11
      bilateral) FMD stenotic lesions (string of beads, tubular, focal) were isolated
      (32) or associated with elongation (tortuosity, coiling, kink) in 24 cases, FDM
      aneurysms (7), and dissecting pseudoaneurysms (9). The surgical techniques
      included graduated or balloon intra-luminal dilatation either isolated (29) or
      associated with resection-anastomosis (35), saphenous graft (4) and
      reconstructive aneurysmorrhaphy (4). Bifurcation endarterectomy was combined in
      14 patients. There was no hospital death. There were 2 neurologic deficits after
      operation (1 transient) and 12 transient nervous disorders due to dissection near
      the base of the skull required in one third of the cases. The follow-up period
      extends from 6 to 22 years. Five patients were lost to follow-up. Out of the 53
      remaining patients, 44 (83%) are living and asymptomatic. Nine patients died: 4
      from myocardial infarction, 3 from cancer, 2 from neurologic disease. Three late
      successful reoperations were observed: 1 aneurysm formation following graduated
      dilatation, 2 anastomotic stenosis. Surgical intraluminal dilatation either
      isolated or combined with reconstructive techniques is a safe and durable
      operation relieving symptoms. The benefits of repair are long lasting and should
      be offered to patients with symptomatic FMD carotid lesions. The medical
      management of asymptomatic cases allows to study the natural history of the
      disease whose causes are not so far fully known.

PMID- 8300710
TI  - Natural history of patients with carotid stenosis waiting for surgical treatment.
AB  - BACKGROUND AND PURPOSE: The natural history of carotid lesions has generally been
      evaluated in anedoctal series or in clinical trials. The purpose of this study
      was to evaluate clinical and pathological modifications linked to an increasing
      waiting list in our region and the related medico-legal implications. METHODS:
      Neurological symptoms that occurred during the waiting period were evaluated in
      282 out of 491 patients placed on the waiting list for a carotid stenosis less
      than 80% or without an unstable plaque. The other 202 patients cancelled their
      booking. Progression of carotid disease was evaluated by duplex scanning in 116
      patients who had a duplex evaluation in our Department both at booking and at the
      time of operation. RESULTS: The incidence of stroke in a mean waiting period of
      8.9 months was 2.6% in symptomatic patients and 1.5% in asymptomatic,
      respectively; 39 (13.8%) patients experienced an ipsilateral TIA and 4.2% a
      carotid thrombosis (25% of which symptomatic). The crude mortality-rate was 2.4%
      with a 1% of related deaths. The cumulative actuarial hard end points rate
      (stroke, carotid thrombosis and related death) was 7.8% at 12 months and 19.8% at
      18 months. CONCLUSIONS: This study gives us data about the natural history of
      carotid stenosis in our country. The high morbidity and mortality-rate related to
      this lesion and particularly their occurrence within the first 3 months stress
      the urgency of treatment, and of the planning of specialized Departments in
      relation to the real incidence of the pathology in order to avoid medico-legal
      consequences.

PMID- 8300711
TI  - Microcirculatory effects of elastic stockings in diabetic microangiopathy: a 24
      week study.
AB  - Patients with diabetic microangiopathy were studied by laser-Doppler flowmetry-
      measuring skin blood flux at rest (RF) and the venoarteriolar response (VAR) and
      evaluating the rate of ankle swelling (RAS) to study capillary filtration. After
      randomisation, 38 patients were treated for 24 weeks with below-knee elastic
      stockings, and 36--acting as controls--were left without elastic compression.
      After 12 and 24 weeks, there were no significant changes in the control group,
      while there was a significant improvement of the microcirculatory parameters in
      patients using stockings. RF (increased at the beginning of the study) was
      significantly decreased, the VAR (impaired at the beginning of the study)
      improved significantly and the abnormally increased capillary filtration
      decreased. Elastic stockings seem to be useful in diabetic microangiopathy
      improving microcirculatory parameters and decreasing capillary filtration and
      oedema. These effects may improve diabetic microangiopathy and possibly slow down
      its rate of progression.

PMID- 8300713
TI  - Acute effects of intermittent sequential compression in venous hypertension.
AB  - Chronic venous hypertension produces microangiopathy which often progresses to
      ulceration. It has been recently observed that intermittent sequential
      compression (ISC) increases the rate of healing of venous ulcers. The aim of this
      study was to investigate the effect of this form of therapy on the
      microcirculation in limbs with venous hypertension. Skin blood flow at rest (RF)
      was measured by laser Doppler flowmetry at the perimalleolar region at rest
      (horizontal position) and on standing in 34 limbs with chronic venous
      hypertension (17 with ulcerations) and 20 limbs of healthy volunteers. The
      venoarteriolar response (VAR = the vasoconstrictory response on standing) was
      also measured. Also 8 limbs with venous hypertension not treated with ISC were
      studied to evaluate the effects of supine resting alone on the microcirculation.
      Two treatment protocols were used. In Study 1 intermittent sequential compression
      was applied for 30 minutes. Laser-Doppler measurements were performed at time 0
      (before intermittent sequential compression) and after 30, 60 and 90 minutes. In
      Study 2 intermittent sequential compression was applied for 60 minutes and
      measurements were performed at time 0 and after 60 and 120 and 180 minutes. In
      patients of Study 1 RF was 1.45 +/- 0.8, significantly higher than in normals (p
      < 0.05) and the venoarteriolar response only 7%, significantly lower than in
      normals. At the end of the compression period there was a marked change towards
      normality as RF decreased (1.1 +/- 0.2) while the change in venoarteriolar
      response was not significant. At 60 and 90 minutes the changes in RF were still
      significant (p < 0.05) and the VAR was significantly increased (p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300712
TI  - Cerebral metabolism and effects of pulsatile flow during retrograde cerebral
      perfusion.
AB  - We evaluated cerebral metabolism during retrograde cerebral perfusion (RCP) and
      circulatory arrest under profound hypothermia, and also investigated the effect
      of pulsatile flow on RCP. Eighteen adult mongrel dogs were placed on
      cardiopulmonary bypass and were cooled to a nasopharyngeal temperature of 20
      degrees C. At this temperature, hypothermic circulatory arrest (HCA; n = 6), non
      pulsatile RCP (NP-RCP; n = 6), and pulsatile RCP (P-RCP; n = 6) were performed
      for 60 minutes. Retrograde cerebral perfusion was performed via the bilateral
      internal maxillary veins, and retrograde flow rate was regulated to maintain a
      mean perfusion pressure of 20 mmHg in the external jugular vein. During RCP, the
      temperature was maintained in a narrow range, oxygen consumption and carbon
      dioxide excretion could be observed, the excess lactate was maintained at a
      negative value, and cerebral tissue ATP concentration was significantly higher
      than in the HCA group. The cerebral tissue water content was significantly lower
      in the P-RCP group than in the NP-RCP group. These findings suggest that
      hypothermia of the central nervous system, the supply of oxygen, the excretion of
      metabolites, aerobic metabolism, and the cerebral ATP level were maintained by
      RCP. In conclusion, RCP may possibly provide adequate metabolic support for the
      brain during total circulatory arrest, and pulsatile flow appears to reduce
      cerebral edema when compared with non-pulsatile flow in dogs.

PMID- 8300714
TI  - Anatomical interrelation between the phrenic nerve and the internal mammary
      artery as seen by the surgeon.
AB  - Paresis of the diaphragm (especially left-side paresis) is a relatively frequent
      finding following cardiac surgery. While, usually, it is a rather benign
      condition, in exceptional cases it may lead to severe impairment to death of the
      patient. The supposed causes of damage to the phrenic nerve include: local
      myocardial cooling by ice slush; opening of the pleural cavity in connection with
      local cooling; cross clamp length; total hypothermia; central venous cannulation;
      traction-related damage; mammary artery harvesting. Perhaps the commonest cause
      of damage to the phrenic nerve, i.e., the effect of local myocardial cooling by
      ice slush, and the mode of phrenic nerve protection have been studied in
      considerable detail. The authors focused their attention on the interrelation
      between the phrenic nerve and the proximal segment of the mammary artery. Using
      anatomical preparations, the authors demonstrate the very intimate relationship
      of the above entities. The interrelation of the two anatomical structures
      basically differs depending on whether the left or right side is concerned. 1) On
      the left: The phrenic nerve, on entering the thorax, runs between the subclavian
      artery and vein laterally from the mammary artery crossing it medially; it parts
      the latter and continues in mediastinal adipose tissue to run on the pericardium
      toward the diaphragm. 2) On the right: The phrenic nerve passes between the
      subclavian vein and artery medially from the mammary artery. For another 3-4 cm,
      it runs along the medial and dorsal edges of the mammary artery.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8300715
TI  - Treatment of a distal splenic artery aneurysm with splenic conservation. A case
      report.
AB  - We report the case of a successful treatment of a splenic artery aneurysm by
      aneurysm excision and direct splenic artery reconstruction allowing spleen
      conservation. This aneurysm was related to an arterial wall medianecrosis.
      Because of the reappraisal of the splenic immunological function, we believe as
      others that this surgical management can be a new alternative to splenectomy as
      treatment of splenic artery aneurysms.

PMID- 8300716
TI  - Isolated blunt trauma of the common carotid artery.
AB  - We present the case of an isolated rupture of the common carotid after a non
      penetrating trauma of the neck. The patient was diagnosed by auscultation,
      ultrasound examination and arteriography and subsequently operated. A carotid
      segment was resected and reconstructed by an interposed vascular graft. We
      comment on the mechanisms of carotid artery blunt trauma, diagnostic methods and
      surgical options in this uncommon situation.

PMID- 8300717
TI  - Isolated true atherosclerotic aneurysms of the superficial femoral artery. Case
      report and literature review.
AB  - Isolated true atherosclerotic aneurysms of the superficial femoral artery are
      rare. We report an original case of superficial femoral artery aneurysm (SFAA)
      not associated with dilatation of the common femoral or popliteal artery. The
      review of the literature emphasizes the great latency of the disease and the high
      incidence of complication at presentation, as well as, echosonographic
      diagnostical advantages over angiography. After surgical treatment the prognosis
      is favourable. Early recognition and surgical repair are recommended for patients
      with aneurysms of the superficial femoral artery greater at least twice the
      normal vessel size. Elective surgical treatment is associated with little risk to
      the patients and avoids the need for operation in the setting of limb-threatening
      ischemia.

PMID- 8300718
TI  - Results of coronary artery bypass grafting using multiple arterial conduits.
AB  - Between January 1991 and June 1993, a total of 128 patients underwent coronary
      artery bypass grafting employing multiple autologous arterial conduits, including
      157 internal mammary arteries, 69 inferior epigastric arteries, 44 gastroepiploic
      arteries, and 72 radial artery grafts. Their mean age was 61.4 years (range 29 to
      82 years). The patients were divided into 2 groups: group A, consisted of 69
      patients (mean age 60.3 years), in whom multiple arterial conduits were used
      exclusively (no vein grafts); group B, included 59 patients (mean age 62.7 years)
      in whom, in addition to multiple arterial conduits, 89 saphenous vein grafts were
      used concomitantly. The mean number of grafts was 3.1 and 3.7, for groups A and
      B, respectively. The preoperative left ventricular function, and the prevalence
      of unstable angina, a recent myocardial infarction, and diabetes, were not
      significantly different between both groups. Our series included 11 "redo"
      operations (8 in group A, and 3 in group B). There were 6 early deaths (4.7%
      mortality) (1 in group A, and 5 in group B), and 4 perioperative myocardial
      infarctions (1 in group A, 3 in group B). During a mean follow-up of 12.9 months
      (range 1 to 28 months) there were no late deaths or reoperations in any group.
      All patients in group A are free of symptoms. In group B, 2 patients have
      recurrent angina, and 1 had a late myocardial infarction, in the distribution of
      a vein graft. A myocardial SPECT scan with exercise revealed new perfusion
      defects in 4 of 49 patients (1 in group A, 3 in group B), studied 1 year after
      surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300719
TI  - Detection of perioperative myocardial structural damage by the estimation of
      cardiac myosin light chain I.
AB  - The accurate estimation of myocardial damage is desirable for the assessment of
      myocardial protection and surgical treatments. The purpose of the study was to
      estimate myocardial damage by measuring cardiac myosin light chain I (CMLCI).
      Forty-nine patients undergoing cardiac surgery (for angina or valvular disease)
      were arbitrarily divided into four groups according to the maximum CMLCI level.
      Group 1: max CMLCI < 10 micrograms/L (37%); Group 2: max CMLCI 10-20 micrograms/L
      (39%); Group 3: max CMLCI 20-30 micrograms/L (16%); Group 4: max CMLCI > 30
      micrograms/L (8%). Electrocardiogram (ECG) and serum creatine kinase MB isoenzyme
      (CK-MB) were conventionally used as standards of myocardial damage, and compared
      with CMLCI. Perioperative myocardial infarction, injury and minimum damage were
      determined by combinations of ECG pattern changes and CK-MB levels. The max CMLCI
      level was usually seen on the third postoperative day. None of the patients in
      group 1 had any ECG changes. The number of patients with ECG changes was much
      higher as the max CMLCI level increased, and evidently increased when the max
      CMLCI was over 20 micrograms/L. The number of patients with high CK-MB > 100
      micrograms/L followed the same pattern. Furthermore, perioperative infarction was
      only seen when the max CMLCI was > 30 micrograms/L. The peak CMLCI level was
      significantly higher in the infarction group than injury and minimum damage
      groups. This study showed that CMLCI was able to estimate the actual extent and
      severity of the myocardial damage and enhanced the diagnosis of perioperative
      infarction.

PMID- 8300720
TI  - Technique of sequential grafting the left internal mammary artery (LIMA) to the
      circumflex coronary system.
AB  - The most common grafting technique performed with the IMA's is to anastomose the
      LIMA to the Left Anterior Descending (LAD) coronary system. With the expanded use
      of this conduit, the Right IMA (RIMA) can be used to graft the LAD system and the
      LIMA can be routed to the Circumflex (Cx) coronary system. This is the most
      common graft design in case of coronary disease affecting the LAD and the
      circumflex systems. The technique used at the Medical Center "The Klokkenberg"
      since 1989 to route the LIMA to the marginal arteries through a pericardial
      window is described in detail.

PMID- 8300721
TI  - How to do it. A modified battery-powered toothbrush for coronary artery
      endarterectomy.
AB  - A modified battery-powered toothbrush for performing coronary artery
      endarterectomy is described. The device facilitates the dissection of the
      atheromatous core, is safe and inexpensive.

PMID- 8300723
TI  - Thoracoscopic treatment of spontaneous pneumothorax. A review.

PMID- 8300722
TI  - Epithelioid hemangioendothelioma of the heart with distant metastases. A case
      report and literature review.
AB  - Epithelioid hemangioendothelioma is an uncommon intermediate-grade vascular tumor
      which most often presents in soft-tissue and is known to occasionally
      metastasize. A primary cardiac occurrence of this tumor was resected from the
      left atrium of a 71 year-old woman. Four months later, she underwent gluteal
      exploration and resection of three nodules from her right buttock. These nodules,
      which resembled the previously resected tumor but showed features of malignant
      transformation, were identified as metastatic epithelioid hemangioendotheliomas.
      To the best of our knowledge, only one case of primary cardiac epithelioid
      hemangioendothelioma has been previously reported in the literature. We believe
      ours is the second such case and the first to demonstrate distant metastases.
      This rare case of primary cardiac epithelioid hemangioendothelioma with distant
      metastases is illustrative of many of the known features and behaviors of the
      tumor. The case is reviewed and discussed alongside a review of recent topical
      literature.

PMID- 8300724
TI  - Biomechanics and biology of fracture repair under external fixation.
AB  - The major factors determining the mechanical milieu of a healing fracture under
      external fixation, and thereby the mechanism of union, are the rigidity of the
      selected fixation device, the fracture configuration, the accuracy of fracture
      reduction, and the amount of physiologic stresses dictated by functional activity
      and loading. Bone healing problems encountered in fractures stabilized externally
      merely reflect the severity of the local soft-tissue and periosteal injury and
      should not be attributed to the inherent features of the fixation modality.
      Although some surgeons have had reservations concerning the use of external
      fixation for fracture treatment, based mainly on concerns of pin-tract infection
      and fracture nonunion, much of the clinical experience and basic science research
      results have proven the reverse. Many of the potential benefits of external
      fixation, such as the change of fixation stiffness, are not yet fully
      appreciated. Additional research and well-organized clinical trials must be
      performed. Pin-tract problems can be controlled, but the surgeon using such a
      device must be familiar with the techniques and follow the established regimens
      during postoperative care. One common mistake is to assume that external
      fixators, especially those of the simpler unilateral configuration, are easy to
      use and do not require learning or mastering the surgical techniques until the
      time of application. Periodic examination and radiographic evaluations are also
      essential to adjust conditions of the fracture site. The importance of balancing
      the biomechanical properties and the biologic consequences of different external
      fixation modalities has been demonstrated. Understanding this knowledge and the
      techniques of application associated with external fixation is the prerequisite
      to successful treatment. Some of the basic biomechanical information related to
      external fixation and bone fracture union is still unknown. This lack should
      provide the impetus for surgeons, bioengineers, and medical scientists to
      continue collaborative basic and applied research. Furthermore, by recognizing
      the proper cell mediators and the physical means to stimulate these cellular
      elements, the bone fracture healing process may be modulated, regardless of the
      fixation technique. The result of such effort should provide new modalities to
      improve fracture management.

PMID- 8300725
TI  - Biomechanical properties and design considerations in upper extremity external
      fixation.
AB  - External fixation is an excellent technique for the osteosynthesis of fractures
      affecting the upper extremity. The rational use of the technique is based on
      sound principles of biology and biomechanics. Good pin design and application
      techniques are among the important factors for successful outcome. These factors
      are discussed in this article along with the advantages of external fixation.

PMID- 8300726
TI  - External fixators for treatment of unstable wrist fractures. A biomechanical,
      design feature, and cost comparison.
AB  - This study provides comparative data relative to the mechanical rigidity, cost,
      weight, and other features of 13 external fixators for the distal radius. It is
      our intent that these data be used by the practicing surgeon in the selection of
      a device that is appropriate to his or her practice and any given patient.

PMID- 8300727
TI  - Static external fixation of the wrist.
AB  - Historical evolution in concepts, indications, application, reduction techniques,
      and the rehabilitation program and complications of external fixation of the
      wrist are discussed. Indirect reduction techniques using overdistraction and
      flexion are recommended. Additional stabilization of the epiphysis allows
      immediate reduction of overdistraction, thus eliminating the potential
      complications related to overdistraction. Used with the due attention to detail,
      external fixation of the wrist is a rewarding and efficient treatment method.

PMID- 8300728
TI  - Distal radius fractures. Multiplanar ligamentotaxis.
AB  - Ligamentotaxis is the principle of molding fracture fragments into alignment as a
      result of tension applied across a fracture by the surrounding intact soft
      tissues. Uniplanar ligamentotaxis obtained by longitudinal traction does not
      always restore palmar tilt to the distal radius. Multiplanar ligamentotaxis
      extends the principle of uniplanar ligamentotaxis to include translation of the
      hand in the dorsal-palmar and the radial-ulnar planes to effect appositional and
      tilting alignment of the distal fragment(s) of a fractured radius. Use of an
      external fixator that allows adjustments in multiple planes helps restore
      anatomic alignment and maintain fracture reduction during healing.

PMID- 8300729
TI  - Dynamic external fixation of distal radius fractures.
AB  - External fixation in fractures of the distal radius has been used for almost 80
      years. The main objective is to achieve reduction and maintain the reduction
      throughout treatment. The fixator concept described as the dynamic fixator allows
      reduction in three planes and allows for the wrist to move after a period of
      rigid fixation. Fixator application is illustrated for fractures that necessitate
      bridging of the wrist joint and for extra-articular fractures. Indications for
      additional measures, including bone grafting, k-wire fixation, and stabilization
      of the radioulnar joint, are discussed. Associated injuries and postoperative
      management is described. The technique of correcting malunited fractures with the
      assistance of an external fixator is explained, with special emphasis on the
      correction of radial length, angle, and shift. The results of initial trials show
      a low complication rate and indicate that bone grafting should probably be used
      more than previously recommended.

PMID- 8300730
TI  - Treatment of complex fractures of the distal radius. Combined use of internal and
      external fixation and arthroscopic reduction.
AB  - A group of fractures of the distal radius are inherently unstable and cannot be
      treated by closed reduction and cast or external fixation. These fractures are
      high-energy motor vehicle accidents often seen in young adults but possible in
      nearly every age group. They are not typical Colles's fractures because they are
      intra-articular with displacement of the joint articular surfaces. The goals of
      treatment are to obtain an anatomic reduction and then to proceed with treatment
      techniques to maintain the reduction by whatever methods are available or
      necessary within the experience of the treating surgeon. Previous admonitions
      that Colles's fractures should not be treated by open reduction are incorrect.
      Like other intra-articular fractures, the goal is anatomic alignment. Limited
      open reduction or newer arthroscopic techniques may be sufficient. A more
      aggressive approach of open reduction, internal and external fixation, and
      autogenous bone grafting is now indicated in most high-energy distal radius
      fractures to achieve the treatment goals defined earlier: anatomic joint surface
      reduction, restoration of radial length, and correction of dorsal malangulation.

PMID- 8300731
TI  - External fixation for open fractures of the upper extremity.
AB  - Recent advances in external fixation hardware, frame application, and pin-site
      care have resulted in the evolution of external fixation as a safe and versatile
      technique. It provides skeletal stability, access to the site of injury, and
      allows early mobilization. It avoids the disadvantages of additional soft-tissue
      stripping and the foreign body introduction associated with internal fixation of
      open fractures. The utility of external fixation principles in open hand and
      wrist fractures is well established. Indications for external fixation in open
      fractures of the forearm, elbow, and arm are more restricted. External fixation
      in these locations should probably be limited to situations of marked fracture
      comminution, bone loss, or extensive soft-tissue damage.

PMID- 8300732
TI  - Technique and results of external fixation of complex carpal injuries.
AB  - This article reviews the current indications and technique of external fixation
      of the wrist for complex carpal trauma. The results obtained in 24 consecutive
      patients with an average follow-up of 2.4 years are also presented.

PMID- 8300733
TI  - Static fixation of finger fractures.
AB  - Static fixation of the fingers by external fixators means external stabilization
      of a fractured digit or phalanx or preservation of length of the affected
      segments until bone grafting and bone healing are achieved. During the treatment
      course, distraction or compression are not applied to the callus. The static
      fixation does not mean the lack of dynamic influences, it depends on the
      mechanical characteristics of the device applied. Our mini external stabilizer
      compared with the former rigid fixators can be considered a semiflexible, and
      therefore semidynamic, device owing to its metallurgic characteristics, which are
      proved by the secondary bone healing achieved in our clinical cases.

PMID- 8300734
TI  - Static external fixation of finger fractures.
AB  - In spite of its similar design constructs, external fixation of finger fractures
      differs greatly from that of long bones. Besides its common indications in
      massive, high-energy trauma, and contaminated fractures, it offers true
      alternatives to open reduction and internal fixation and represents a superior
      treatment modality in well-selected cases of extensive comminution. Further
      pending improvement in design will increase its application, although it
      apparently does not yet resolve long-standing controversies in elective fracture
      care.

PMID- 8300735
TI  - Dynamic external fixation for fractures of the proximal interphalangeal joint.
AB  - This article presents the relevant anatomy of the proximal interphalangeal joint
      and the determination of its axis of joint motion. Based on findings of a single
      axis of motion, the principles and indications for dynamic external fixation are
      presented. Illustrative cases and results are shown.

PMID- 8300736
TI  - External fixation for treatment of hand infections.
AB  - The indications for external fixation in the treatment of hand infections are
      limited; however, external fixation, which is considered to be a salvage
      procedure, has many advantages in selected cases, such as severely contaminated
      open injuries, septic nonunions, and advanced septic arthritis with segmental
      bone loss and skin defects. External fixation can be used in different ways and
      must be included in a planned program for the treatment of bone infection.

PMID- 8300737
TI  - Small joint arthrodesis.
AB  - Arthrodesis of the joints of the digital skeleton may be readily accomplished by
      using small external fixators. Although it is effective for almost any
      indication, it is perhaps best used for open injury, infection, and other
      difficult circumstances when different methods of compression arthrodesis are
      inadvisable. Fusion rates are very high, with successful first-attempt external
      fixation arthrodesis occurring in at least 96% of cases as reported in prior
      publications. Length of immobilization varied from 6 to 8 weeks with an acrylic
      and K-wire compression device to 8 to 10 weeks with a Manuflex device. Other
      reports demonstrate similar results.

PMID- 8300738
TI  - External fixation for the treatment of Kienbock's disease.
AB  - With the advent of magnetic resonance imaging, the diagnosis of avascular
      necrosis of carpal bones can be made early, well before collapse and derangement
      of carpal mechanics occur. We believe that neutralization of forces early in the
      course of disease may permit natural healing (revascularization) of the bone. It
      is questionable whether tubular casts can supply adequate neutralization of
      force. We recommend the consideration of external fixation, rather than more
      extensive surgery, as a rational alternative for this purpose. After surgical
      revascularization, carpal bones go through a resorptive phase that makes them
      highly susceptible to collapse from compressive forces across the wrist. We
      advocate the postoperative use of an external fixator to neutralize these forces
      after a revascularization procedure is performed.

PMID- 8300739
TI  - Digital lengthening. With emphasis on distraction osteogenesis in the upper limb.
AB  - Digital lengthening, commonly practiced for hand digits of segments, seldom for
      those of the foot, has been much enhanced by new applications of old techniques
      and some surprising physiologic responses to those techniques.

PMID- 8300740
TI  - The gradual correction of forearm deformities in multiple hereditary exostoses.
AB  - Careful preoperative planning, fixator selection and design, surgical technique,
      and sustained follow-up care are essential for successful gradual correction of
      pediatric forearm deformities. The sequence of planning gradual deformity
      correction can be created by establishing a problem list and using this as the
      basis for design of the gradual correction. Viewing limb length and deformity
      correction as a "process," rather than a procedure, is of value. Using a hybrid
      fixation formula that combines half pins with wires can minimize the potential
      for neurovascular injury. The combination of radial osteotomy, excision of
      osteochondromas, and gradual ulnar lengthening by distraction osteogenesis
      improves forearm appearance and function in most patients with multiple
      hereditary exostoses.

PMID- 8300741
TI  - Distraction arthroplasty of the elbow.
AB  - One of the most common and potentially disabling complications of elbow trauma is
      that of posttraumatic stiffness. The type of surgery best suited to the patient's
      need is a function of the existence of joint surface involvement (intrinsic or
      extrinsic). For intrinsic causes, distraction with or without interposition
      arthroplasty has altered functional outcome. What was thought to be a virtually
      untreatable complication has now been treated with an aggressive surgical release
      and distraction to achieve an acceptable result.

PMID- 8300742
TI  - Applications of the Ilizarov method in the humerus. Lengthenings and nonunions.
AB  - Between 1982 and 1992, Ilizarov's method was used in 68 lengthenings and 29
      nonunions of the humerus. Special rings along with the arches similar to those
      used for femoral lengthening were used to allow unrestricted motion at the elbow
      and shoulder. These patients were followed for an average of 5.1 years. In cases
      of lengthening, average length achieved was 9 cm, with duration of treatment
      being 5 to 14 months. Overall results in most cases were excellent. In cases of
      nonunion, the duration of treatment averaged 226 days. Of the 29 nonunions, 25
      healed. Our results, including no major complications, support the continued use
      of Ilizarov's technique in humeral lengthening and nonunions of the humerus.

PMID- 8300743
TI  - Cytokines: molecular keys to homeostasis, development, and pathophysiology.
AB  - Identification and definition of the role and diversity of action of cytokines,
      the regulatory proteins including lymphokines, monokines, interleukins,
      interferons, and a variety of other growth factors produced by virtually every
      nucleated cell into the body and having pleiotropic regulatory effects on
      hematopoietic and many other cell types [Thompson, 1991], are in the forefront of
      biomedical research. The explosive development of cytokine research is reflected
      by the inclusion of "cytokine," first introduced as a term in 1974 to recognize
      that lymphokines could be produced by other than lymphoid cells in 4,267
      biomedical articles published by the end of 1992. From the initial reference to
      cytokines in 1974 to inclusion in 45 articles in 1985, the doubling of citations
      each succeeding year, together with 45% of all the citations since 1974 occurring
      in 1992 alone, attests to the continued rapid expansion of this area of
      biological research. The important roles of cytokines in many physiological
      processes and pathophysiological conditions, although largely descriptive in
      nature, were recognized during the early development of this field of
      investigation [Balkwill and Burke, 1989; Cohen et al., 1974]. Current and future
      directions, as highlighted by the series of Prospect articles featuring areas as
      diverse as embryologic, extracellular matrix, bone, hematologic, and neurologic
      development and function as well as in the organism's response to foreign
      organisms in this issue of the Journal, are focused on broadening our
      understanding of the positive and negative influence of cytokines in normal and
      abnormal differentiation and development and on the molecular pathways underlying
      cytokine action.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300744
TI  - Activities of growth factors in preimplantation embryos.
AB  - The development of the mammalian preimplantation embryo in vitro occurs more
      slowly and less successfully compared to development in the uterus. The fact that
      it can occur at all in a defined protein-free medium suggests that the process is
      autonomous. Accumulated evidence indicates that a number of peptide growth
      factors contribute in an autocrine fashion to preimplantation development. Other
      growth factors are maternally derived and act in a paracrine manner on the
      embryo. Some of these factors such as insulin-related factors stimulate growth
      preferentially, but others such as epidermal growth factor (EGF) play more
      important roles in differentiation. Several cytokines appear to be implicated in
      peri-implantation events and in maternal-fetal interactions. At this stage, the
      data are mostly descriptive. Are all these different growth factors and receptors
      necessary for early development? Some implications of apparent redundancy of gene
      expression are discussed and future studies are predicted.

PMID- 8300745
TI  - Cytokine regulation of metalloproteinase gene expression.
AB  - Matrix metalloproteinases belong to a family of zinc-dependent enzymes capable of
      degrading extracellular matrix and basement membrane components. Their expression
      is greatly modulated by cytokines and growth factors and involves the gene
      products of the Fos and Jun families of oncogenes. After extra(peri)cellular
      activation, their activity can be further controlled by specific tissue
      inhibitors of metalloproteinases. A correct balance between these regulatory
      mechanisms is necessary to ensure matrix remodeling in normal physiological
      processes such as embryonic development, but the overexpression of these enzymes
      may initiate or contribute to pathological situations such as cartilage
      degradation in rheumatoid arthritis or to tumor progression and metastasis.
      Delineation of the mechanisms of metalloproteinase and metalloproteinase
      inhibitors gene expression, understanding of their mode of interactions, and
      characterization of their patterns of expression in various tissues in normal and
      pathological states will lead to new therapeutic strategies to counteract the
      deleterious effects of matrix metalloproteinases in human disease.

PMID- 8300746
TI  - Role of cytokines in bone resorption.
AB  - Osteoclastic bone resorption is modulated in humans by powerful osteotropic
      factors which are generated in the immediate vicinity of bone resorbing surfaces.
      These factors are released from marrow mononuclear cells and from some bone
      cells, and some are actually incorporated into the noncollagenous bone matrix
      from where they are released when bone is resorbed. They are likely important not
      only in the control of normal bone remodeling, but also in a number of disease
      states associated with disordered remodeling. In this review, current concepts of
      the effects of these factors on cells in the osteoclast lineage will be
      discussed.

PMID- 8300747
TI  - Cytokine cross-talk between phagocytic cells and lymphocytes: relevance for
      differentiation/activation of phagocytic cells and regulation of adaptive
      immunity.
AB  - Cytokines represent one of the most important elements in the communication among
      different cell types. They play an increasingly better understood role in the
      communication among hematopoietic cells and in particular in the reciprocal
      regulation of effector cell types of innate or natural resistance (phagocytic
      cells and Natural Killer (NK) cells) and those of adaptive immunity (T and B
      lymphocytes). Lymphocytes produce several cytokines with either stimulatory
      (e.g., colony stimulatory factor) or suppressive (e.g., tumor necrosis factors
      and interferons) effects on proliferation of early hematopoietic cells. Many of
      these cytokines, alone or acting in synergistic combinations, also have a
      differentiation-inducing ability on immature myeloid cells and act as powerful
      potentiators of the cellular functions of terminally differentiated phagocytic
      cells. The communication between lymphocytes and phagocytic cells is not
      unidirectional, as phagocytic cells produce factors that regulate lymphocyte
      activation. In addition to their role as antigen presenting cells expressing
      costimulatory accessory molecules and secreting cytokines (e.g., IL-1, IL-6,
      TNF), phagocytic cells have been recently shown to produce Natural Killer cell
      Stimulatory Factor (NKSF/IL-12). IL-12 is a heterodimeric cytokine with important
      modulatory functions on cytotoxicity of NK and T cells, lymphocyte proliferation,
      lymphokine production, and development of T helper cell subsets. These
      communications between phagocytic cells and lymphocytes are further regulated by
      negative and positive feedback mechanisms that contribute to maintain the
      homeostasis of the system in physiologic conditions and to govern the changes in
      this equilibrium needed for the response to infectious or other foreign agents.

PMID- 8300748
TI  - Hypothalamic releasing hormones mediating the effects of interleukin-1 on sleep.
AB  - There is a substantial literature describing the interactions between the
      endocrine and immune systems. Although such interactions are less well known
      within the brain, one major brain function altered during inflammation and
      infection and by several endocrine hormones is sleep. Pathological disturbances,
      be they inflammation, infectious disease, and/or sleep deprivation, result in
      altered hypothalamus-pituitary function and cytokine metabolism. In respect to
      hormone secretion from the pituitary, cytokines are now recognized to play an
      important role in modulating the neuroendocrine system. Changes in sleep provide
      a useful illustration of the interactions between cytokines and the hypothalamus
      pituitary axis. Evidence linking interleukin-1 (IL-1) to growth hormone releasing
      hormone and to corticotropin releasing hormone in regard to their effects on
      sleep is reviewed.

PMID- 8300749
TI  - TGF-beta 1 is an organizer of responses to neurodegeneration.
AB  - TGF-beta 1 mRNA and protein were recently found to increase in animal brains
      after experimental lesions that cause local deafferentation or neuron death.
      Elevations of TGF-beta 1 mRNA after lesions are prominent in microglia but are
      also observed in neurons and astrocytes. Moreover, TGF-beta 1 mRNA autoinduces
      its own mRNA in the brain. These responses provide models for studying the
      increases of TGF-beta 1 protein observed in beta A/amyloid-containing
      extracellular plaques of Alzheimer's disease (AD) and Down's syndrome (DS) and in
      brain cells of AIDS victims. Involvement of TGF-beta 1 in these human brain
      disorders is discussed in relation to the potent effects of TGF-beta 1 on wound
      healing and inflammatory responses in peripheral tissues. We hypothesize that TGF
      beta 1 and possibly other TGF-beta peptides have organizing roles in responses to
      neurodegeneration and brain injury that are similar to those observed in non
      neural tissues. Work from many laboratories has shown that activities of TGF-beta
      peptides on brain cells include chemotaxis, modification of extracellular matrix,
      and regulation of cytoskeletal gene expression and of neurotrophins. Similar
      activities of the TGF-beta's are well established in other tissues.

PMID- 8300750
TI  - Adenovirus genes that modulate the sensitivity of virus-infected cells to lysis
      by TNF.
AB  - TNF is a key inflammatory cytokine with antiviral properties. Human adenoviruses
      encode several intracellular proteins that mediate the effects of TNF. Expression
      of the adenovirus immediate early E1A proteins induces viral genes and a host of
      cellular genes, drives G0 cells into S-phase, and induces apoptosis and
      susceptibility to TNF-induced apoptosis. The adenovirus E1B-19K protein inhibits
      both E1A- and TNF-induced apoptosis. The E3-14.7K protein and the E3-10.4K/14.5K
      complex of proteins inhibit TNF- but not E1A-induced apoptosis. The E3 14.7K and
      10.4K/14.5K proteins inhibit TNF activation of cytosolic phospholipase A2
      (cPLA2), which may explain how they inhibit TNF cytolysis. Since eicosinoids
      produced from arachidonic acid (the product of cPLA2) are potent mediators of
      inflammation, the E3 proteins may block the inflammatory response to adenovirus
      infection. These adenovirus proteins should be novel tools to understand
      adenovirus pathogenesis, TNF signal transduction, and TNF cytolysis.

PMID- 8300751
TI  - Cytokine involvement in viral permissiveness and the progression of HIV disease.
AB  - Many viruses have evolved novel means of exploiting host defense mechanisms for
      their own survival. This exploitation may be best exemplified by the
      interrelationships between certain viruses and the host cytokine networks. Many
      viruses, including the human immunodeficiency virus type-1 (HIV-1), rely on the
      liberation and cellular action of host immune cytokines to expand their host cell
      range, to regulate their cellular expression, and to maintain their dormant state
      until the proper extracellular conditions arise. As again exemplified by HIV-1,
      viruses may also take an active role regulating cytokine expression and cell
      surface cytokine receptors. Because the viral life cycle, and in particular the
      HIV-1 life cycle, is so intertwined with cytokine regulatory networks, these
      networks represent potential points for therapeutic intervention. As our
      understanding of cellular cytokine pathways involved in viral infection and
      replication continues to expand, so too will our ability to design rational anti
      viral therapies to alter multiple steps along the viral life cycle.

PMID- 8300752
TI  - Regulation of angiotensin I-converting enzyme in cultured bovine bronchial
      epithelial cells.
AB  - The purpose of this study was to determine whether angiotensin I-converting
      enzyme (ACE) is present in cultured bovine bronchial epithelial cells (BBECs) and
      whether its activity can be modulated. We found that extracts of confluent
      monolayers of cultured BBECs degraded [glycine-1-14C]hippuryl-L-histidyl-L
      leucine at a rate of 843 +/- 66 pmol/hr/mg protein (mean +/- SEM, n = 5). In
      addition, we found that the enzyme was shed into the culture medium. ACE activity
      in BBECs was inhibited by three selective, but structurally different, ACE
      inhibitors (captopril, quinapril, and cisalaprilat) with an IC50 of approximately
      2 nM. Increasing chloride concentration in the assay buffer resulted in an
      increase in BBECs ACE activity of 63%. Enzyme activity was also modulated by the
      presence of zinc cation in the assay buffer. Addition of dexamethasone to the
      culture medium was associated with a significant increase in BBECs ACE activity
      (P < 0.05), which was inhibited by the steroid receptor antagonist RU 38486.
      Western blot analysis of BBECs, tracheal and bronchial mucosal strips utilizing a
      cross-reacting rabbit anti-mouse ACE antibody, showed a faint 175 kDa band and
      additional strong 52 kDa and 47 kDa band. The mechanism of generation of the low
      M.W. bands is unknown. Our data indicate the presence of ACE in cultured BBECs
      and that enzyme activity can be modulated.

PMID- 8300753
TI  - Modulation of human microvascular endothelial cell bioenergetic status and
      glutathione levels during proliferative and differentiated growth.
AB  - During angiogenesis, formerly differentiated human microvascular endothelial
      cells (HMECs) return to a proliferative growth state. Many fundamental questions
      regarding HMEC function, such as how HMECs adapt to changes in bioenergetic
      requirements upon return to proliferative growth, remained unanswered. In this
      study, we evaluated whether modifications in HMEC bioenergetic profiles and
      glutathione (GSH) levels accompanied the cellular transition between
      differentiated and proliferative growth. To provide insight into the continuum of
      cellular adaptations that occur during this transition, we used a method recently
      developed in our laboratory that induces a state of morphological and functional
      predifferentiation in HMECs. Cellular morphology, in conjunction with flow
      cytometric DNA analyses and HMEC functional assays (the directed migration and
      intercellular association involved in microtubule formation) were employed to
      validate the HMEC culture state of growth. Analysis of the HPLC nucleotide
      profiles disclosed several findings common to all culture growth states. These
      uniform findings, e.g., cellular energy charges > 0.90, and highly reduced redox
      states, revealed that cultured HMECs maintain high rates of oxidative metabolism.
      However, there were also significant, culture growth state related differences in
      the nucleotide profiles. Proliferative HMECs were shown to possess significantly
      higher (relative to both large vessel endothelial cells, and differentiated
      HMECs) levels of GSH and specific nucleotides which were related with a return to
      the active cell cycle-ATP, GTP, UTP, and CTP, and NADPH. Further, the nucleotide
      profiles and GSH levels of the predifferentiated HMECs were determined to be
      intermediate between levels obtained for the proliferative and differentiated
      HMECs. The results of this study demonstrate that the capacity to modulate their
      cellular bioenergetic status during growth state transitions is one of the
      adaptations that enable HMECs to retain a growth state reciprocity. In addition,
      our findings also show that HMECs, especially during the proliferative growth
      state, are biochemically distinct from endothelial cells harvested from large
      vessels, and therefore suggest that HMECs are the cells of choice to employ when
      studying diseases that affect the human microvasculature.

PMID- 8300754
TI  - Nuclear localization of melatonin in different mammalian tissues:
      immunocytochemical and radioimmunoassay evidence.
AB  - Melatonin was detected by an improved immunocytochemical technique in the cell
      nuclei of most tissues studied including several brain areas, pineal gland,
      Harderian gland, gut, liver, kidney, and spleen from rodents and primates.
      Cryostat sections from tissues fixed in Bouin's fluid, formalin, or
      acetone/ethanol were used. The nuclear staining appeared primarily associated
      with the chromatin. The nucleoli did not exhibit a positive reaction. The
      melatonin antiserum was used in the range of 1:500 to 1:5,000. Incubation of the
      antibody with an excess of melatonin resulted in the complete blockade of nuclear
      staining. Pretreatment of the sections with proteinase K (200-1,000 ng/ml)
      prevented the positive immunoreaction. In a second aspect of the study, we
      estimated the concentration of melatonin by means of radioimmunoassay in the
      nuclear fraction of several tissues including cerebral cortex, liver, and gut.
      The subcutaneous injection of melatonin (500 micrograms/kg) to rats resulted,
      after 30 min, in a rapid increase in the nuclear concentration of immunoreactive
      melatonin which varied in a tissue-dependent manner. However, samples collected 3
      h after the injection showed that melatonin levels had decreased to control
      values. Pinealectomy in rats resulted in a clear reduction in the nuclear content
      of melatonin in the cerebral cortex and liver but not in the gut. The results of
      these studies suggest that melatonin may interact with nuclear proteins and that
      the indole may have an important function at the nuclear level in a variety of
      mammalian tissues.

PMID- 8300756
TI  - Estrogen receptor-negative breast cancer cells transfected with the estrogen
      receptor exhibit increased RAR alpha gene expression and sensitivity to growth
      inhibition by retinoic acid.
AB  - We and others have shown previously that retinoic acid (RA) selectively inhibits
      the growth of estrogen receptor (ER)-positive human breast carcinoma (HBC) cells
      and ER-negative cells are refractory to RA inhibition of growth. The ER-negative
      cells inherently express lower levels of RAR alpha and retinoic acid response
      element (RARE)-mediated RA-induced CAT activity. In this study we report that
      when ER-negative MDA-MB-231 cells were transfected with the ER gene they not only
      expressed higher levels of RAR alpha and RARE-mediated RA-induced CAT gene
      expression, but their growth was not inhibited by RA. Estrogen enhanced RAR alpha
      gene expression not only in established ER-positive cell lines but also in ER
      transfected MDA-MB-231 cells. The estrogen effect appears to be direct and at the
      gene transcription level since it did not alter the stability of RAR alpha mRNA
      and cycloheximide failed to block estrogen-mediated enhancement of RAR alpha gene
      expression. Our data strongly suggest that ER-mediated enhancement of RAR alpha
      levels plays an important role in RA inhibition of HBC growth. In addition, we
      also report here that HBC cells appear to express a unique isoform(s) of RAR
      alpha which was detected only when the full-length RAR alpha cDNA was used as a
      probe; the RAR alpha 1 and RAR alpha 2 specific probes failed to hybridize with
      the HBC specific RAR alpha message.

PMID- 8300755
TI  - Immunohistochemical localization of the avian progesterone receptor and its
      candidate receptor binding factor (RBF-1).
AB  - An avian oviduct nuclear matrix protein in the 6-10 kDa size range has been
      implicated to function in the cell-free nuclear binding of the avian oviduct
      progesterone receptor (PR). This protein, termed the receptor binding factor-1
      (RBF-1), has been purified and partially characterized [Schuchard et al.:
      Biochemistry 30:4535-4542, 1991]. This paper describes the immunohistochemical co
      localization of the RBF-1 and PR in the avian oviduct cell nuclei and rat
      reproductive cell nuclei using antibodies directed specifically against the RBF-1
      and activated PR. In the undifferentiated oviduct, the immunoreactivities for
      both PR and RBF-1 were co-localized in the nuclei of only epithelial cells, but
      not the stromal cells or smooth muscle cells. In the partially differentiated
      oviduct of estrogen treated chicks, the immunoreactivity co-localized in the
      nuclei of not only epithelial but also glandular and stromal cells. Staining for
      the PR, but not RBF-1, was detected in the smooth muscle cells. The intensity of
      the PR but not the RBF-1 staining was markedly down-regulated in these cells at 2
      and 6 h after treatment of the animals with progesterone (P). However, the band
      patterns for RBF-1 in the Western blots did show qualitative changes which may
      reflect P-induced posttranslational modifications which alter the epitope on the
      RBF-1. Interestingly, immunohistochemical analysis of several reproductive
      tissues of the rat showed that certain cell types in the uterus, ovary, and
      prostate displayed strong positive nuclear staining for an RBF-1-like
      antigen(s).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300757
TI  - Further purification and characterization of a multienzyme complex for DNA
      synthesis in human cells.
AB  - The 21 S complex of enzymes for DNA synthesis in the combined low salt nuclear
      extract-post microsomal supernatant from HeLa cells [Malkas et al. (1990)
      Biochemistry 29:6362-6374] was purified by poly (ethylene glycol) precipitation,
      Q-Sepharose chromatography, Mono Q Fast Protein Liquid Chromatography (FPLC), and
      velocity gradient centrifugation. The procedure gives purified enzyme complex at
      a yield of 45%. The 21 S enzyme complex remains intact and functional in the
      replication of simian virus 40 DNA throughout the purification. Sedimentation
      analysis showed that the 21 S enzyme complex exists in the crude HeLa cell
      extract and that simian virus 40 in vitro DNA replication activity in the cell
      extract resides exclusively with the 21 S complex. The results of enzyme and
      immunological analysis indicate that DNA polymerase alpha-primase, a 3',5'
      exonuclease, DNA ligase I, RNase H, and topoisomerase I are associated with the
      purified enzyme complex. Denaturing polyacrylamide gel electrophoresis of the
      purified enzyme complex showed the presence of about 30 polypeptides in the size
      range of 300 to 15 kDa. Immunofluorescent imaging analysis, with antibodies to
      DNA polymerase alpha,beta and DNA ligase I, showed that polymerase alpha and DNA
      ligase I are localized to granular-like foci within the nucleus during S-phase.
      In contrast, DNA polymerase beta, which is not associated with the 21 S complex,
      is diffusely distributed throughout the nucleoplasm.

PMID- 8300758
TI  - Purification of a novel glycosylated ferritin from horse heart.
AB  - We have previously shown that mRNA coding for ferritin L subunit is present on
      both cytosolic ribosomes and endoplasmic reticulum-bound ribosomes in rat heart
      tissue [Campbell et al. (1989) Arch Biochem Biophys 273:89-98]; from this we
      infer that heart tissue is capable of making a secreted ferritin. We now report
      the purification from horse heart, of a ferritin that specifically binds to
      Concanavalin A-Sepharose and is immunologically cross-reactive with antibodies
      raised against both horse cellular ferritin and horse serum ferritin. Where
      cellular ferritin is 10 nm in diameter and contains primarily 21-kDa subunits (as
      determined by gel exclusion chromatography and electron microscopy), the
      glycosylated heart ferritin is smaller with diameters of 3-5 nm. Antisera raised
      against serum ferritin cross-reacted with the glycosylated heart ferritin did but
      did not show significant cross-reactivity with cellular ferritin thus indicating
      that serum ferritin and glycosylated heart ferritin have antigenic determinants
      which may not be present on cellular ferritin. The glycosylated ferritin also
      differs from cellular ferritin in subunit composition, with subunits of 66, 60.5,
      53.5, 43.5, and 29.5 kDa, as shown by SDS-PAGE and Western blot analysis.
      Interestingly, ferritin purified from horse serum contains subunits of similar
      size.

PMID- 8300759
TI  - Refractory hypotension after heart attack.

PMID- 8300760
TI  - Chronic viral hepatitis: diagnosis and management.
AB  - Most patients with chronic hepatitis are infected with the B or C virus.
      Diagnosis has been simplified with the advent of increasingly accurate assays.
      Treatment, however, is still less than ideal; only about 50% of patients respond
      to alpha-interferon, and the rate of relapse is particularly high in hepatitis C.
      Refinements in patient selection criteria and treatment modalities are on the
      horizon.

PMID- 8300761
TI  - Syncope in a man with COPD.

PMID- 8300762
TI  - Rash, arthropathy, and fatigue in a young woman.

PMID- 8300763
TI  - AIDS: human rights and responsibilities.
AB  - As epidemiology changes and new therapies emerge, the focus of disease control is
      shifting from the voluntary to the mandatory. This is reflected in debates about
      routine HIV testing of newborns and the confidentiality of HIV-infected adults.
      Other issues include access to unproven drugs, the problems posed by co-infection
      with TB, and prevention through needle and condom distribution.

PMID- 8300764
TI  - Biting the hand.

PMID- 8300765
TI  - Current issues in ovarian cancer.

PMID- 8300766
TI  - New strategies to prevent hip fracture.

PMID- 8300767
TI  - Neural-immunologic interactions in asthma.
AB  - Recent investigations offer insights into the possible cause of asthma: Rather
      than being due to either neural or immunologic events, the fault may lie in
      concurrent malfunctioning of two interacting systems. Antigenic stimulation, for
      example, can affect neural depolarization and firing; by the same token, nerve
      stimulation can affect the growth and function of inflammatory cells.

PMID- 8300768
TI  - Chronic iron deficiency anemia of unknown etiology.

PMID- 8300769
TI  - Breast cancer: 1. Screening and early management.
AB  - A 53-year-old woman presented to her physician one month after she had noticed an
      area of "thickening" in the upper outer quadrant of her right breast. The patient
      had had her last menstrual period two years earlier. She had never had a
      mammogram. A mammogram was performed. It showed an area of clustered
      microcalcifications suggestive of cancer in the area of the palpable abnormality.

PMID- 8300770
TI  - Toward a national hepatitis B vaccination program.

PMID- 8300771
TI  - The treatment of urinary incontinence.

PMID- 8300772
TI  - Early phonological and lexical development and otitis media: a diary study.
AB  - This diary study describes early phonological and lexical development in a child
      with chronic otitis media with effusion. Equipped with the tools of a
      referential/analytic language-learner, the child solved the problem of reduced
      and fluctuating auditory input with phonological selection and avoidance
      strategies that capitalized on prosodic cues. This 'tone-language' approach
      resulted in a lexical inventory that would be categorized as an extreme
      expressive style. Having 'boot-strapped' her lexical learning, the child
      continued to rely on phonological constraints and selection strategies to fuel
      lexical and syntactic growth, i.e. cross-domain interactions leading to a
      vocabulary spurt and the onset of two-word utterances. These findings illustrate
      the need to consider interactions among performance, input and linguistic
      constraints in order to explain individual variation in language learning.

PMID- 8300773
TI  - Vowel dominance in overregularizations.
AB  - When children produce regularizations like comed, not all verbs are equally
      likely to be regularized. Several variables (e.g. lexical frequency) have been
      shown to be relevant, but not all the variability between verbs is understood. It
      is argued here that one predictor is which vowels are present in the base form
      vs. the past tense form. Using a notion of recessive vs. dominant vowel (where
      recessive vowels are more likely to be replaced by dominant vowels than vice
      versa) based on adult phonological processing, it is predicted that
      regularizations should be likely when the base vowel is dominant and unlikely
      when the past tense vowel is dominant. Data from 17 children reported in the
      literature, aged 1;6-5;6, show that this prediction is correct. Implications for
      the role of phonological variables in the processing of irregular past tense
      forms are discussed.

PMID- 8300774
TI  - Early lexical development in Spanish-speaking infants and toddlers.
AB  - This paper describes the early lexical development of a group of 328 normal
      Spanish-speaking children aged 0;8 to 2;7. First the development and structure of
      a new parent report instrument, Inventario del Desarollo de Habilidades
      Communicativas is described. Then five studies carried out with the instrument
      are presented. In the first study vocabulary development of Spanish-speaking
      infants and toddlers is compared to that of English-speaking infants and
      toddlers. The English data were gathered using a comparable parental report, the
      MacArthur Communicative Development Inventories. In the second study the general
      characteristics of Spanish language acquisition, and the effects of various
      demographic factors on that process, are examined. Study 3 examines the
      differential effects of three methods of collecting the data (mail-in, personal
      interview, and clinic waiting room administration). Studies 4 and 5 document the
      reliability and validity of the instrument. Results show that the trajectories of
      development are very similar for Spanish- and English-speaking children in this
      age range, that children from varying social groups develop similarly, and that
      mail-in and personal interview administration techniques produce comparable
      results. Inventories administered in a medical clinic waiting room, on the other
      hand, produced lower estimates of toddler vocabulary than the other two models.

PMID- 8300775
TI  - Reanalysing rote-learned phrases: individual differences in the transition to
      multi-word speech.
AB  - The present study investigates the possibility that the previously documented
      relationship between referential-expressive and nominal-pronominal styles
      (Nelson, 1975) may be best explained not so much in terms of 'object-orientation'
      or 'noun-preference', as in terms of the direction from which different children
      break into structure, with some children tending to construct patterns by
      combining two or more items from their single-word vocabularies and others
      tending to develop patterns by gaining productive control over 'slots' in
      previously unanalysed phrases. In order to do so it makes use of a methodology
      for distinguishing between productive and unanalysed multi-word speech proposed
      in Lieven, Pine & Dresner-Barnes (1992) which is applied to observational and
      maternal-report data from a longitudinal study of seven children between the ages
      of 0;11 and 1;8. The results suggest not only that variation in children's early
      word combinations can indeed be explained in terms of different routes to multi
      word speech, but also that, far from being atypical, a strategy involving the
      breaking down of originally unanalysed phrases may be used by all children,
      though to varying degrees.

PMID- 8300776
TI  - Pronoun reversals: who, when, and why?
AB  - Seventeen of a sample of 30 precocious talkers aged 1;8 produced at least one
      pronoun reversal (I/you) during unstructured play. This finding led to an
      examination of the role of cognitive and linguistic individual differences as
      well as contextual factors and processing complexity as determinants of pronoun
      reversal. Contrary to predictions derived from previous hypotheses, there were
      few differences between reversers and non-reversers, other than higher use of
      second person forms by reversers. Reversals were more likely to occur in certain
      contexts: semantically reversible predicates with two noun phrases, and in
      imitations (though the rate of imitation was lower overall in reversers). We
      propose that pronoun reversals commonly result from a failure to perform a
      deictic shift, which is especially likely when children's psycholinguistic
      processing resources are taxed. Children who did not produce any pronoun
      reversals tended to avoid pronoun use, especially second person forms. Overt
      reversal may thus reflect a risk-taking approach to language acquisition, which
      may be particularly characteristic of precocious children.

PMID- 8300777
TI  - Event knowledge and early language acquisition.
AB  - The role of event knowledge in early language acquisition was investigated.
      Thirteen two-year-olds were observed interacting with their mothers over a five
      week period. During weekly observational sessions, dyads interacted in both a
      familiar-event context and an unfamiliar-event context. Events were represented
      by complex toys (e.g. airport, marina, etc.). In the familiar-event, dyads
      interacted with the same event-toy during each observation period. In the
      unfamiliar-event, these same dyads interacted with a different novel toy during
      each observation period. The results indicated that children's increasing event
      knowledge facilitated their language development. Specifically, children's
      lexical type use, action verb use, and MLU increased in the familiar-event, but
      remained unchanged in the unfamiliar-event. Event knowledge also facilitated
      children's lexical token use. Results are discussed in terms of the role of event
      knowledge in language acquisition.

PMID- 8300778
TI  - On the origins of denial negation.
AB  - These are the principal questions of this study: are the early functions of
      negation, such as REJECTION, and the later emerging DENIAL no developmentally
      related? And when do children start to deny? So far, evidence for the questions
      at hand has been almost exclusively observational. We decided on a simple
      elicitation procedure instead, asking 48 children (ages between 1;1 and 2;7) easy
      yes/no-questions. The most likely age range for the appearance of denial no was
      1;8-2;1. Its error-free acquisition supports the continuity theory of negation
      development, which holds that essentials of denial no carry over from the earlier
      functions of no. Finally an attempt is made to account for the beginnings of
      denial in terms of semantics and the representational theory of child cognition.

PMID- 8300779
TI  - Uses of past forms in the social pretend play of Italian children.
AB  - In different languages children have been found to use past verb forms to express
      the meaning of 'unreality' during social pretend play. In this study, the verb
      forms used by 14 four-year-old Italian children in their pretend play were
      investigated. Results show that different Italian past verb forms tend to co
      occur with different play activities. The imperfect occurs mainly when children
      plan and negotiate their pretend activities and marks the transition from a real
      to a pretend frame of reference. The present perfect occurs mainly when children
      implement their plans and communicate within a pretend frame that has already
      been established. Results of this study are discussed in comparison with findings
      on the pretend language of children speaking other languages.

PMID- 8300780
TI  - Marking of verb transitivity by Hebrew-speaking children.
AB  - The study examines children's command of transitivity permutations in Hebrew,
      where a change in verb-argument syntax entails a change in verb-morphology. 30
      children aged two, three and eight were required to produce existing and novel
      Hebrew verbs differing in transitivity. Younger children showed a good grasp of
      the syntax and semantics, but not the morphological marking of transitivity,
      three-year-olds did much better, and eight-year-olds produced mainly adult-like
      responses. Results were higher on existing verbs than on novel forms. Direction
      of change had little effect with existing verbs, but with novel verbs success was
      much higher in changing intransitive to transitive forms than the converse. Some
      alternations proved easier than others, e.g. intransitive activity verbs in the
      basic pa'al verb-pattern yielded more causative hif'il forms than intransitive
      inchoative verbs in the nif'al pattern. Findings throw light on the development
      of derivational morphology, item-based versus class-based learning, and the
      impact of lexical productivity and language-particular properties on acquisition.

PMID- 8300781
TI  - Remembered voices.
AB  - The speech children spontaneously quote was examined in two studies. In Study 1,
      a corpus of personal narratives from 96 children aged 4;0 to 9;0 was analysed;
      Study 2 investigated reported speech in 25 younger children aged 1;2 to 5;2
      interacting with their parents. In both studies, the frequency of reported speech
      increased with age. Direct quotation was more common than indirect or summarized
      quotation at all ages. In Study 1, children quoted themselves more frequently
      than any other speaker, and their mothers more frequently than their fathers.
      Directives were the most commonly reported speech act from the distant past in
      both older (Study 1) and younger (Study 2) children. In Study 1, girls used
      reported speech more frequently than did boys, and their quotations were more
      direct in form than were those of boys.

PMID- 8300782
TI  - Phonological devices in poems by English and Italian children.
AB  - Poems were elicited from 133 English children between two and six and 171 Italian
      children between three and seven, using a similar technique, and the results were
      compared. Both groups produced large numbers of poems. There were great
      similarities and some differences. The majority of poems in both samples
      contained phonological devices (mostly rhyme and alliteration) and the proportion
      was higher (87%) in the Italian sample than in the English sample (59%). The
      proportion of poems that contained rhyme was close to 45% in each sample, with no
      consistent age difference in either sample. About one-third of Italian poems and
      just over a fifth of English poems contained alliteration. The frequency of
      alliteration declined with age in the English sample but not in the Italian
      sample. Possible reasons for the differences between the samples are considered.
      It is argued that the similarities are more important, and their theoretical
      implications are discussed.

PMID- 8300783
TI  - The acquisition of Italian morphology: a reply to Hyams.

PMID- 8300784
TI  - Determination of catecholamines in urine and plasma by on-line sample
      pretreatment using an internal surface boronic acid gel.
AB  - An automated method of analysis of catecholamines using a new packing material,
      internal surface boronic acid gel, was developed. The new support is designed
      with a carboxymethylcellulose-bonded external surface in order to be non
      adsorptive to proteins and with a phenylboronic acid-bonded internal surface to
      retain only catecholamines. This packing support displayed an affinity for basic
      or neutral catecholic compounds with no protein adsorption and enabled on-line
      sample pretreatment of catecholamines in urine and deproteinized plasma. The
      catecholamines were selectively adsorbed on the new material and separated on a
      reversed-phase or a cation-exchange column. These compounds were then detected
      electrochemically. The limits of quantitation were 1.5-3.0 ng/ml in urine and 10
      15 pg/ml in plasma, at a signal-to-noise ratio of 5.

PMID- 8300785
TI  - Apometallothionein in rat liver.
AB  - The identification of apometallothionein (AMT) in rat liver by reversed-phase
      high-performance liquid chromatography (RP-HPLC) after gel permeation was
      realized in experiments performed both in vivo and in vitro. The reliable
      assignment of the corresponding AMT peak permitted the detection and
      determination of AMT in different groups of experimental and control rats. In all
      animals studied (more than 100 rats), AMT was always present in amounts higher
      than that of metallothionein (MT) or compatible with it. Induction of MT
      synthesis by CdCl2 subcutaneous injections decreased the AMT level and increased
      the MT level, but nevertheless the amount of AMT still remained relatively high.

PMID- 8300786
TI  - Direct injection assay of drug enantiomers in serum on ovomucoid-bonded silica
      materials by liquid chromatography.
AB  - A high-performance liquid chromatographic (HPLC) method for the determination of
      drug enantiomers in serum was developed. The method involves direct injection of
      serum samples on to an ovomucoid-bonded column, which is prepared by bonding of
      ovomucoid proteins to an aminopropyl-silica gel by the N,N'-disuccinimidyl
      carbonate activation method and separation of drug enantiomers on the column
      using a mixture of phosphate buffer and an organic solvent. High recoveries of
      serum proteins were obtained using eluent pH values of 3, 4, 6 and 7 at phosphate
      buffer concentrations above 50 mM, whereas the recovery was ca. 70% at an eluent
      pH of 5. The recovery of each enantiomer of basic and acidic drugs from serum was
      almost 100%.

PMID- 8300787
TI  - High-performance liquid chromatographic determination of a potent AII receptor
      antagonist (DMP 811) in plasma.
AB  - An HPLC assay for DMP 811, 4-ethyl-2-propyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4
      yl)methyl]imi dazole-5- carboxylic acid (I) in rat and dog plasma has been
      developed. Compound I was isolated from plasma using a liquid-liquid back
      extraction procedure. The extraction recovery was greater than 81%. Separation of
      I from endogenous components in plasma was achieved on an E. Merck C8 column
      using a mobile phase of 0.05 M ammonium acetate, brought to pH 3.75 with acetic
      acid, and acetonitrile (78:22, v/v). The eluent was monitored by fluorescence
      with excitation and emission set at 235 and 370 nm, respectively. The assay was
      linear from 2 to 2000 ng/ml. Inter- and intra-day coefficients of variation for
      the rat-plasma assay ranged from 0.9 to 5.2% (5-2000 ng/ml) and 2.7 to 16.5% (2
      2000 ng/ml), respectively. The respective coefficients of variation for the dog
      plasma assay were 1.9 to 5.6% and 1.2 to 14.0%. The percent differences from the
      accuracy results were 12% or less. Using 0.5 ml of plasma for extraction, the
      minimum quantifiable limit was 2 ng/ml. This method has been used to quantify
      plasma levels of I in rats or dogs following 3-10 mg/kg i.v. or p.o. doses.

PMID- 8300788
TI  - Determination of a new antibacterial agent (Ro 23-9424) by multidimensional high
      performance liquid chromatography with ultraviolet detection and direct plasma
      injection.
AB  - Analysis of a new antibacterial agent, Ro 23-9424 (I), in plasma has been
      complicated by the fact that its metabolite, fleroxacin (II), is formed not only
      in vivo, but also nonenzymatically by the hydrolysis of the ester bond of I. In
      order to minimize sample preparation time and possible hydrolysis during sample
      preparation, a high-performance liquid chromatographic procedure was developed
      which features direct injection of plasma and multidimensional chromatography.
      The first dimension size-exclusion separation allows plasma proteins to elute
      with the column void volume. The second dimension reversed-phase column provides
      a high-resolution separation dependent upon the hydrophobicity of the sample
      species. With a 5-microliters injection, the limit of quantitation of the method
      is 0.35 microgram/ml for I and 0.27 microgram/ml for II. The method was used to
      determine steady state plasma vs. time profiles for I and II from 750 mg i.v.
      doses of I administered twice daily.

PMID- 8300789
TI  - Enantioselective high-performance liquid chromatographic determination of (SR)-
      and (RS)-mefloquine in plasma using N-benzyloxycarbonyl-glycyl-L-proline as
      chiral counter ion.
AB  - A stereoselective HPLC method is described for the determination of (SR)- and
      (RS)-mefloquine in plasma. The direct chiral separation is carried out on a
      Hypercarb-S column (porous graphitised carbon) with N-benzyloxycarbonyl-glycyl-L
      proline (L-ZGP) as a chiral counter-ion in a reversed-phase system. The sample
      work-up included protein precipitation by addition of zinc sulphate and
      acetonitrile followed by liquid-liquid extraction with methyl-tert.-butyl ether.
      After evaporation of the organic phase, the residue is dissolved in the mobile
      phase and injected onto the column. Analyses of the enantiomers in plasma after a
      single oral dose of mefloquine indicates that the pharmacokinetics of the two
      enantiomers are different. The method is validated by determining the absolute
      recovery, linearity, accuracy, precision and inter- and intra-assay variation.

PMID- 8300790
TI  - Determination of exemestane, a new aromatase inhibitor, in plasma by high
      performance liquid chromatography with ultraviolet detection.
AB  - A sensitive and selective high-performance liquid chromatographic method for the
      determination of 6-methylen-androsta-1,4-diene-3,17-dione (exemestane) and its 17
      dihydro metabolite in human plasma has been developed. The analytes and internal
      standard (Norgestrel) were extracted from plasma samples with a methylene
      chloride-iso-octane mixture; the organic phase was dried and the residue was
      reconstituted with an acetonitrile-water mixture, then analyzed by reversed-phase
      liquid chromatography. Quantification was achieved by ultraviolet detection of
      the eluate. The linearity, precision and accuracy of the method were evaluated.
      No interference from the constituents of human blank plasma was observed. The
      lower limit of quantification was 10 ng/ml plasma. The suitability of the method
      for in vivo samples was checked by analysis of plasma samples drawn from healthy
      male volunteers who had received a 200-mg single oral dose of the test compound.

PMID- 8300791
TI  - Determination of the new podophyllotoxin derivative NK 611 in plasma by high
      performance liquid chromatography with ultraviolet detection.
AB  - A high-performance liquid chromatographic method has been developed for the
      determination of the new podophyllotoxin derivative NK 611 in plasma samples. A
      solid-liquid extraction procedure with C18 extraction columns was used for
      extraction of plasma samples containing NK 611. The adsorbed NK 611 was eluted
      from the extraction columns with methanol-acetonitrile (50:50, v/v). The elution
      liquid was injected into a reversed-phase system consisting of a Chrompack C18
      column. The mobile phase was acetonitrile-20 mM phosphate buffer, pH 7 (30:70,
      v/v). The UV detection mode allows sensitive determination of NK 611 in plasma
      within phase I trials. The limit of detection was 10 ng/ml, the limit of
      quantitation 35 ng/ml (for 1 ml of extracted plasma and 20-microliters injection
      volume). The calibration curve is linear within the concentration range 100-1000
      ng/ml. The recovery of NK 611 from spiked plasma samples was approximately 80%.

PMID- 8300792
TI  - Determination of phenylmercapturic acid in urine of benzene-exposed BDF-1 mice.
AB  - This paper describes a procedure for the identification of phenylmercapturic acid
      in urine of benzene-exposed mice. Collected urine of benzene exposed mice was
      adjusted to pH 7 and applied to an anion exchanger. After extraction with diethyl
      ether and evaporation to dryness, the sample was dissolved in aqueous phosphoric
      acid and injected into the HPLC. HPLC conditions included an ODS column and an
      eluent consisting of tetrabutylammoniumhydrogensulfate-methanol (75:25, v/v), the
      absorbance wavelength was 255 nm. The detection limit of phenylmercapturic acid
      was 3 mg/l in mouse urine.

PMID- 8300793
TI  - Identification of mycotoxins in keratomycosis-derived Fusarium isolates by gas
      chromatography-mass spectrometry.
AB  - The production of mycotoxins from Fusarium species has been demonstrated in
      isolates cultured from patients suffering from keratomycosis. The method employed
      a combination of thin-layer chromatography directly performed on gel plugs taken
      from the growth medium, cartridge column chromatography, silylation and gas
      chromatography on a non-polar stationary phase capillary column linked to mass
      spectrometry. The sensitivities of detection obtained for a signal-to-noise ratio
      of 33:1, were 200 pg for single stage GC-MS and 20 pg using tandem GC-MS-MS. Two
      mycotoxins, diacetoxyscirpenol and T-2 toxin were identified in three cultures.

PMID- 8300794
TI  - Comparison of immunoaffinity chromatography combined with gas chromatography
      negative ion chemical ionisation mass spectrometry and radioimmunoassay for
      screening dexamethasone in equine urine.
AB  - A comparison of the sensitive analytical methods of radioimmunoassay (RIA) and
      immunoaffinity chromatography (IAC) combined with gas chromatography-negative ion
      chemical ionisation mass spectrometry for the specific and reliable screening of
      dexamethasone in equine post-race urine is presented. Results from analyses of
      samples collected from a mare during 144 hours post administration of 26 mg of
      dexamethasone sodium phosphate are described.

PMID- 8300795
TI  - Simple high-performance liquid chromatographic method to verify the direct
      barbituric acid assay for urinary cotinine.
AB  - An isocratic HPLC method is described to determine urinary concentrations of
      nicotine and cotinine after derivatization with cyanogen chloride and barbituric
      acid. This method has been used to assess the reliability of the direct
      barbituric acid assay to determine smoking status. It is concluded that the
      direct barbituric acid assay is a very reliable indicator of smoking status,
      provided that urine blank samples are prepared to correct for background
      absorbance. If the direct barbituric acid assay is in disagreement with self
      reported smoking status, this HPLC procedure is a useful method to resolve the
      discrepancy.

PMID- 8300796
TI  - Determination of plasma propofol levels using gas chromatography-mass
      spectrometry with selected-ion monitoring.
AB  - Propofol (2,6-diisopropylphenol, I.C.I. 35,868) is a rapid-acting, intravenous
      anesthetic agent recently introduced for the induction and maintenance of general
      anesthesia. This paper describes a gas chromatographic-mass spectrometric
      procedure using selected-ion monitoring for the determination of plasma propofol
      levels. The drug and the internal standard (thymol) were extracted from plasma
      into diethyl ether-pentane, and derivatized to their trimethylsilyl derivatives
      before analysis. The reproducibility of the daily standard curves had
      coefficients of variation ranging from 2.7% to 10.2%. The precision of the assay
      yielded a coefficient of variation ranging from 4.5% to 5.6%, and the
      concentration means for the seeded control samples were found to be within -1.6%
      to +0.6% of the theoretical values for propofol. No interfering peaks have been
      observed in application of this procedure to either normal volunteer or patient
      samples. The minimum detectable level under the conditions described was 0.20 ng
      propofol/ml plasma. This assay and a high-performance liquid chromatographic
      assay with fluorescence detection were both used to measure plasma propofol
      concentrations in 89 human plasma samples, and the correlation between the two
      methods was excellent.

PMID- 8300797
TI  - Determination of plasma tocopherols by high-performance liquid chromatography
      with coulometric detection.
AB  - An HPLC procedure has been developed for tocopherol determination with
      coulometric detection in human serum samples. Eluent optimization and foreign
      peak identification (bilirubin) by mass spectrometry are described. An extraction
      procedure gave yields around 98% with 1.3% coefficient of variation, and the
      calibration ranged from 0.1 to 200 mg/l with a correlation coefficient of 0.999.
      The detection limit achieved for vitamin E was 60 pg (3 ng/ml).

PMID- 8300798
TI  - Sensitive high-performance liquid chromatographic method for the determination of
      coumarin in plasma.
AB  - A high-performance liquid chromatographic method was developed for the
      determination of coumarin in plasma at low concentrations. The method involves a
      single-step extraction of the alkalinized sample with hexane and subsequent
      evaporation of the organic phase in the presence of hydrochloric acid to collect
      and concentrate the coumarin. Analysis of the acidic phase was performed on a C8
      column and coumarin was detected by measuring the UV absorbance at 275 nm. The
      limit of detection was 0.3 microgram l-1. The assay was used to study the
      evolution of concentrations of coumarin in one volunteer after oral
      administration of a single 10-mg dose.

PMID- 8300799
TI  - Simple direct injection high-performance liquid chromatographic method to
      determine quinidine in plasma.
AB  - High-performance liquid chromatographic methods that use direct injection of
      plasma include column-switching procedures, modified mobile phases and small-pore
      modified stationary phases. By using a large-pore (300 A) Selectosil C18 column,
      developed for the analysis of macromolecules, we have shown that quinidine in
      plasma and protein solutions can be assayed accurately and rapidly by directly
      injecting 2 microliters plasma or protein solution onto the column. Column life
      is not reduced, and the limit of quantitation is 0.01 microM.

PMID- 8300800
TI  - Rapid high-performance liquid chromatographic method for the determination of
      ketamine and its metabolite dehydronorketamine in equine serum.
AB  - A simple, rapid and sensitive high-performance liquid chromatographic procedure
      has been developed for the determination of ketamine and dehydronorketamine in
      equine serum. Sample preparation consisted of mixing equal volumes of serum and
      acetonitrile-phosphoric acid (85%)-water (20:2:78, v/v/v), followed by
      ultrafiltration through a 10,000 molecular mass cut-off filter. Separation of
      these two analytes in the ultrafiltrate was accomplished on a reversed-phase
      phenyl column eluted with methanol-acetonitrile-phosphate buffer solution.
      Ketamine and dehydronorketamine were detected by a variable photometric UV-Vis
      detector set at 215 nm, and confirmed by a photodiode array detector operated in
      the 200-320 nm range. The limit of detection for ketamine was 5-15 ng/ml in
      equine serum. Additionally, the dehydronorketamine peak identity was tentatively
      confirmed by thermospray liquid chromatography-mass spectrometry.

PMID- 8300801
TI  - Ethical issues in gender selection by X/Y sperm separation.

PMID- 8300802
TI  - A child is a joy at any age.

PMID- 8300803
TI  - Pregnancies are acceptable in post-menopausal women.

PMID- 8300804
TI  - Prenatal sex determination and selection.
AB  - The advent of the polymerase chain reaction technique has revolutionized the
      science of prenatal diagnosis including sex selection. The technique is now
      available to identify the sex of human preimplantation embryos after in-vitro
      fertilization or to determine the sex of a fetus by non-invasive methods. Where
      medical indication exists, selected female embryos can be transferred to the
      uterus and thus prevent unnecessary termination of an established pregnancy.
      However, these methods might be used for non-medical purposes as well. The
      developments in this field which have occurred during the last decade, as well as
      the moral dilemmas which accompany these advantages, are discussed in this paper.

PMID- 8300805
TI  - Blastocysts prepare for the race to be male.
AB  - Recent findings in different mammalian species have demonstrated that XY embryos
      grow faster than XX embryos before the gonads are differentiated. In mice and
      cattle, accelerated development is already evident in XY blastocysts, while in
      the rat and in human fetuses a quantitative sex difference has been shown to be
      present before testicular differentiation has occurred. These data demonstrate
      that in these species the histological differentiation of the testis, which
      occurs early and rapidly, is preceded by an increased growth rate of the embryo.
      This may be expected to increase the probability of the gonad reaching the
      threshold for testis development, since it is known that developmental delay can
      result in ovarian differentiation. It is postulated that the fast development of
      the male may be an adaptation to the reproductive biology of eutherian mammals,
      in which development of both sexes occurs in the hormonal environment of the
      uterus. The question is raised as to a possible connection between sex-related
      growth and other sex differences, such as longevity.

PMID- 8300806
TI  - Second messenger pathways in the regulation of cell function.

PMID- 8300807
TI  - Electromechanical activities of human uteri during extra-corporeal perfusion with
      ovarian steroids.
AB  - A new experimental system was designed to study human uterine activities based on
      the extra-corporeal perfusion of isolated human uteri. Electromechanical
      activities in the uterine wall were recorded using bipolar silver-silver
      electrodes, endoluminal pressure catheters and a dedicated acquisition, storage
      and analytical system. The electrical signals recorded were isolated spikes and
      rhythmic activities; the last being primarily associated with organized
      mechanical events. Perfusion media containing 17 beta-oestradiol alone or with
      progesterone were used for those uteri obtained during proliferative (n = 5) or
      secretory (n = 5) phases of the menstrual cycle, respectively. Progesterone
      caused a reduction of frequency (P < 0.001) and duration (P < 0.001) of the
      rhythmic electrical activity, and decreased the endoluminal pressure at both
      detection sites (P < 0.01). 17 beta-Oestradiol increased both frequency (P <
      0.001) and duration (P < 0.001) of the rhythmic electrical activity as well as
      the endoluminal pressure at two different detection sites (3 and 5 cm from the
      fundus) (P < 0.05). Significant differences between the fundus and cervix sites
      in the uterine wall were detected. In conclusion, uterine perfusion would be
      useful to examine the effects of uterotonic and tocolytic drugs before
      administration to humans, at no risk to the patients. Oestrogens increase and
      progesterone decreases both electrical and mechanical uterine activities.

PMID- 8300808
TI  - Human follicular fluid maturity and endothelial cell mitogenesis.
AB  - Follicular fluid, of varying maturity, (day 5-16 of cycle) was collected from the
      largest Graafian follicle of each of 22 ovulatory patients during laparoscopic
      procedures. Three samples were blood-stained and discarded. The mitogenic
      potential of each sample was determined using bovine aortic endothelial cells in
      the CellTiter 96 Non-Radioactive Cell Proliferation/Cytotoxicity Assay system.
      Intra- and inter-plate coefficients of variation were < 9%. The follicular fluid
      samples induced cell doubling times which varied from approximately 12-24 h and
      final cell numbers which, in the individual wells, ranged from 7828-30,900
      (starting number 2000/well). Follicular fluid total protein content was unrelated
      to the mitogenic potential, (R2 = 0%). Serum oestradiol was negatively correlated
      with the mitogenic potential (R2 = 26%). No correlation was found with day of the
      menstrual cycle (R2 = 4.3%), maximum follicular diameter (R2 = 1.8%), or serum
      concentration of progesterone (R2 = 0.7%), luteinizing hormone (LH) (R2 = 1.5%)
      or follicle stimulating hormone (R2 = 0.1%). Five subjects were in 'early' and
      six in 'mid'-follicular phase, six were in 'early' and two in 'late' LH surge.
      There was no difference in the mitogenic response between these four groups by
      one-way analysis of variance (F = 0.21; P = 0.89). It is concluded that the
      mitogenic potential of human follicular fluid is not related to Graafian follicle
      maturity or, more particularly, to the LH surge.

PMID- 8300809
TI  - Ion transport by human endometrial epithelia in vitro.
AB  - Human glandular endometrial epithelial cells were cultured on porous tissue
      culture inserts to form tight, confluent layers. These layers generated time
      dependent modifications in the ionic composition of both apical and basolateral
      solutions. Increases in sodium and chloride concentrations in the basolateral
      fluid were accompanied by reciprocal decreases in the concentrations of these
      ions in the apical fluid. The potassium concentration was increased in the
      apical, while decreased in the basolateral, solution. The total calcium
      concentration was slightly elevated in the apical, as compared with the
      basolateral fluid, while there were no alterations in pH. The endometrial layers
      demonstrated a significant transepithelial potential difference, and when this
      value was substituted in the Nernst equation a prediction of the passive
      distribution of ions across the cells was possible, indicating that none of the
      ions were in equilibrium. Addition of the sodium channel blocker amiloride to the
      medium bathing the cell layers reduced the modifications in ionic composition of
      apical and basolateral solutions. The data are consistent with other data
      indicating an amiloride-sensitive sodium-absorptive function for the endometrial
      epithelium. The ability of these primary cultures of endometrial epithelial cells
      to reduce the sodium while increasing the potassium concentration of the apical
      fluid is qualitatively in agreement with the low sodium and high potassium
      concentrations reported for human uterine fluid. The data suggest a role for the
      endometrial epithelium in generating and maintaining the distinctive ionic
      composition of the intra-uterine environment.

PMID- 8300810
TI  - Morphological characteristics of preimplantation stage endometrium in the rhesus
      monkey.
AB  - The morphological characteristics of endometrium on day 6 after ovulation of
      conception (group 1) and non-fecund, menstrual (group 2) cycles have been studied
      in the rhesus monkey (n = 30). A conception cycle was distinguished by the
      presence of a developmentally normal, age-stage-synchronized embryo. Thus, 78% of
      the mated cycles (n = 18) yielding synchronous embryos (12 zona-encased and two
      zona-free blastocysts) were used for this study. On day 6 after ovulation, no
      significant changes in the serum concentrations of oestrogen and progesterone
      were seen in conception cycles (n = 14) compared with the non-mated, normal
      ovulatory cycles (n = 12). Morphometric analyses revealed that on day 6 of
      gestation (n = 8), endometrium differed from the corresponding non-mated luteal
      phase (n = 7) with significant increases in epithelial mitosis (P < 0.01), height
      of glandular epithelium (P < 0.05), volume ratio of gland cell to gland (P <
      0.03), degree of pseudostratification (P < 0.02), and higher frequency of
      supranuclear, adluminal accumulation of vacuoles in gland cells (P < 0.05). The
      degree of stromal oedema was higher (P < 0.02) in fecund cycles but there was no
      change in venular diameter. In a separate set of experiments, estimates of tissue
      vascular response revealed a higher (P < 0.02) endometrial extravascular albumin
      space on the same day of gestation; there were no differences, however, in
      endometrial blood volume, or in the number of von Willebrand antigen-positive
      capillaries and small vessels between the two groups (group 1, n = 6; group 2, n
      = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300811
TI  - The effect of growth hormone on granulosa cell function during in-vitro
      fertilization.
AB  - The effect of growth hormone addition to human menopausal gonadotrophin (HMG),
      after pituitary down-regulation, on granulosa cell function, in in-vitro
      fertilization (IVF) was evaluated. Growth hormone or placebo were added in a
      prospective, randomized and double-blind manner to an existing IVF stimulation
      protocol. Forty-two normal ovulatory women (< or = 38 years old) with mechanical
      factor infertility and normal male factor were included in the study.
      Gonadotrophin-releasing hormone agonist (GnRHa) was given from day 21 of the
      previous cycle until human chorionic gonadotrophin (HCG) administration.
      Follicular stimulation with HMG was started after pituitary down-regulation.
      Growth hormone 12 IU/day or placebo were administered on alternate days,
      beginning day 1 until day 7 of HMG treatment. Granulosa cell function was
      evaluated, in all patients, by follicular fluid levels of ovarian steroids and
      insulin-like growth factor-I (IGF-I). In 14 patients, chosen arbitrarily
      granulosa lutein cells were cultured in the presence and absence of additional
      HCG. Follicular fluid levels of oestradiol, progesterone, testosterone and IGF-I
      were similar in both growth hormone and placebo groups. Basal and post-HCG levels
      of oestradiol and progesterone did not differ significantly between the two
      groups of granulosa lutein cell cultures. We conclude that after pituitary down
      regulation, in-vivo administration of growth hormone with HMG in young ovulatory
      women does not seem to affect granulosa cell function when compared to the
      administration of HMG alone.

PMID- 8300812
TI  - The effect of nafarelin on human plasma adrenocorticotrophic hormone and cortisol
      concentrations.
AB  - This study assessed the effects on plasma adrenocorticotrophic hormone (ACTH) and
      cortisol concentrations of 3 months' treatment with intranasal nafarelin 200
      micrograms b.d. in 11 women (aged 26-43 years) for the treatment of endometriosis
      (n = 9), fibroids (n = 1) and pre-menstrual syndrome (n = 1). Serial blood
      samples were taken over 5 h, before and after nafarelin administration on the
      first day of treatment, and after 1 and 3 months' treatment. Control samples were
      taken before and after intranasal placebo administration on the day before
      nafarelin was commenced. The area under the curve (AUC) for mean ACTH
      concentrations at each time point from 0 to 240 min was calculated. There were no
      statistically significant changes in total secretion of either ACTH or cortisol.
      There was a transient rise in ACTH 30-60 min after nafarelin administration on
      the first day of treatment in seven out of 11 women. The rise did not exceed the
      normal range. Seven women with ovarian suppression (oestradiol concentration <
      175 pmol/l by day 28) had consistently lower mean ACTH concentrations at all time
      points than the four remaining women who had oestradiol concentrations 222-880
      pmol/l by day 28. Cortisol concentrations were unaffected by nafarelin. We
      conclude from the results of this study that 3 months' treatment with nafarelin
      has no effects on adrenal function, as assessed by ACTH and cortisol
      concentrations.

PMID- 8300813
TI  - The effect of nalmefene on pulsatile secretion of luteinizing hormone and
      prolactin in men.
AB  - Luteinizing hormone (LH) and prolactin are released in pulses which are
      relatively synchronous in the luteal phase of the menstrual cycle in women. The
      concordance of LH and prolactin pulses in normal men has not been reported. The
      objectives of this study were firstly to determine whether LH and prolactin
      pulses are synchronous in men, and secondly to examine the effects of naloxone
      and a new orally active opiate antagonist, nalmefene, on LH and prolactin release
      in men. Three groups of normal male subjects received saline infusion (control n
      = 5), naloxone infusion (2 mg/h; n = 5) or nalmefene (10 mg p.o.; n = 6). Blood
      samples were collected every 15 min for 2 h before and 6 h after study medication
      for determination of LH, prolactin and testosterone by radioimmunoassay. Both
      naloxone and nalmefene resulted in a significant increase in LH pulse frequency
      and in mean serum LH and testosterone concentrations with no change in LH pulse
      amplitude, prolactin pulse frequency or amplitude. In controls, 61% of LH pulses
      were synchronous with prolactin pulses. There was a decrease in concomitance of
      LH and prolactin pulses with naloxone (48%) and nalmefene (24%; P < 0.025)
      administration. In contrast, 52% of prolactin pulses were concomitant with LH
      pulses in controls, while naloxone (100%) but not nalmefene (67%) resulted in a
      significant (P < 0.01) increase in pulse synchrony. The difference observed
      between naloxone and nalmefene on prolactin--LH pulse synchrony is probably due
      to differential opioid receptor activity at the pituitary and hypothalamic
      level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300814
TI  - Comparative pharmacokinetics of two urinary human follicle stimulating hormone
      preparations in healthy female and male volunteers.
AB  - These studies were designed to compare the pharmacokinetic characteristics of a
      very highly purified urinary human follicle stimulating hormone (FSH-HP)
      preparation (sp. act. approximately 9000 IU FSH/mg of protein), Metrodin HP, with
      a standard urinary FSH preparation Metrodin (FSH). The two preparations were
      administered in a balanced, random-order, cross-over sequence as single doses of
      150 IU, separated by 1 week of washout to 12 female volunteers by i.v. injection
      and to 12 male volunteers by i.m. and s.c. routes. FSH concentrations were
      measured by immunoradiometric assay and by an in-vitro rat granulosa cell
      aromatase bioassay. After an i.v. bolus, the pharmacokinetics of the two FSH
      preparations were identical. Total clearance was 0.5 and 0.15 l/h respectively
      for immunoassay and bioassay data. Immunoassay showed that the two preparations
      were similar for renal clearance (0.1 l/h), volumes of distribution at steady
      state (9 l), distribution and terminal half-lives (2 and 17 h, respectively).
      After parenteral administrations, the absorption half-life of FSH was
      approximately 3 h and the apparent terminal half-life was approximately 1.5 days.
      Both preparations had relative bioavailabilities close to 100% for i.m. and s.c.
      administrations. Immunopurification, which results in a very highly purified FSH
      HP, does not modify the pharmacokinetic properties of FSH. This study also
      confirmed that s.c. and i.m. doses of FSH-HP are equivalent from the
      pharmacokinetic and pharmacodynamic points of view.

PMID- 8300815
TI  - Growth hormone, oestradiol, progesterone and testosterone concentrations in
      follicular fluid after ovarian stimulation with various regimes for assisted
      reproduction.
AB  - Follicular fluid samples and oocytes were obtained from 75 women (87 cycles), who
      participated in an assisted conception programme. Determinations of the
      concentration of oestradiol, progesterone, testosterone and growth hormone were
      performed in all follicular fluid samples. Patients were stimulated with the
      following regimes: group A (24 cycles, 94 samples), human menopausal
      gonadotrophin (HMG) (three ampoules/day) and human chorionic gonadotrophin (HCG);
      group B (23 cycles, 53 samples), HMG/HCG with prednisolone (7.5 mg/day) after
      cycle programming with oral contraceptives; group C (40 cycles, 60 samples),
      buserelin with HMG/HCG. Oestradiol concentrations (mean +/- SEM) were
      significantly higher (P < 0.05) in group A (320.1 +/- 27.3 ng/ml) and those of
      growth hormone in both groups A and C (3.8 +/- 0.2 and 3.2 +/- 0.15 ng/ml,
      respectively), as compared to the other groups, whereas progesterone and
      testosterone concentrations were similar in all groups. The mean concentrations
      of oestradiol, progesterone, testosterone and growth hormone were significantly
      higher (P < 0.01) in follicular fluid with oocytes of intermediate maturity than
      with mature oocytes (382.5 ng/ml, 7847.5 ng/ml, 1704.5 ng/dl and 3.7 ng/ml versus
      217.8 ng/ml, 5488.4 ng/ml, 1313.6 ng/dl and 2.7 ng/ml, respectively). On the
      other hand, only oestradiol concentrations were significantly higher in
      follicular fluid of fertilized compared to non-fertilized oocytes. Concentrations
      of the other hormones analysed, except growth hormone, were similar in follicular
      fluid from pregnant and non-pregnant women after assisted reproduction. Growth
      hormone, on the other hand, was significantly lower (P < 0.05) in follicular
      fluid from pregnant compared to non-pregnant women (2.8 versus 3.5
      ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300816
TI  - Serum pattern of different molecular forms of prolactin during normal human
      pregnancy.
AB  - In this study, the molecular heterogeneity of prolactin was analysed in serum
      from normal women throughout pregnancy. Lectin affinity chromatography and
      denaturing polyacrylamide gel electrophoresis under reducing and non-reducing
      conditions, followed by Western blotting and immunostaining were used to resolve
      and identify the molecular variants of prolactin. During the first trimester,
      large molecular forms (64 and 53 kDa) and those corresponding to glycosylated and
      non-glycosylated prolactin (25 and 23 kDa, respectively) were present either
      under reducing or non-reducing conditions. The 64 and 23 kDa were the predominant
      species at this stage of gestation. As pregnancy progressed, the 64 kDa variant,
      which did not bind to concanavalin A, decreased until disappeared at the third
      trimester of gestation. The unbound/bound ratio of serum prolactin to
      concanavalin A increased only at the third trimester; however, the relative
      proportions of concanavalin A-bound prolactin did not show statistically
      significant changes along the gestational period. The results demonstrated the
      occurrence of changes in the heterogeneity of prolactin during gestation and
      further confirmed previous observations that various forms of non-glycosylated
      prolactin are indeed the predominant species in serum from normal women
      throughout pregnancy.

PMID- 8300817
TI  - The development of functional ovarian cysts during pituitary down-regulation.
AB  - This study investigated the development of functional ovarian cysts during
      pituitary down-regulation prior to in-vitro fertilization (IVF), and identified
      16 cases of cysts in 288 IVF cycles studied. Comparing the patients with
      functional ovarian cysts to the other 272 IVF cycles, there was no significant
      difference in age or incidence of endometriosis but significantly (P < 0.01) more
      patients with cysts had ovulatory dysfunction. The serum progesterone was < 5.7
      nmol/l in all 16 patients with cysts on day 4 of the IVF cycle, and in eight of
      these patients the serum progesterone was < 5.7 nmol/l on the day buserelin was
      commenced. In 10 of the 16 patients with cysts, serum oestradiol concentrations
      remained elevated despite the prolonged use of buserelin, and the cysts were
      aspirated. The aspirate in all cases was clear without any suggestion of
      endometriosis. The cyst aspirates had significantly lower progesterone (P <
      0.001), higher androstenedione (P < 0.01) and similar oestradiol concentrations
      to 10 follicular fluid samples collected at the time of oocyte retrieval. This
      study suggests that functional ovarian cysts may develop during pituitary down
      regulation, and these cysts are follicular cysts rather than persistent corpora
      lutea or endometriomata.

PMID- 8300818
TI  - Triggering of ovulation using a gonadotrophin-releasing hormone agonist does not
      prevent ovarian hyperstimulation syndrome.
AB  - A total of 24 women with primary or secondary infertility due to oligo- or
      anovulation, were treated with human menopausal gonadotrophin (HMG). In 48
      cycles, we used a gonadotrophin-releasing hormone agonist (GnRHa) nasal spray
      (buserelin) to induce a pre-ovulatory endogenous luteinizing hormone (LH) surge.
      In 44 cycles, there was a rapid rise of the serum LH concentration within 8 h
      from the first administration of GnRHa. One patient with pituitary
      hypogonadotrophic amenorrhoea showed a weak or no response in four treatment
      cycles. Conception occurred in 10 cycles (pregnancy/cycle (P/C) index = 22.7%),
      four of which ended in a spontaneous abortion and six of which are ongoing
      pregnancies. In 27 cycles, there was an increased risk for ovarian
      hyperstimulation syndrome (OHSS), defined as more than three follicles > or = 18
      mm in diameter and/or serum oestradiol > 1200 pg/ml. Three of these treatment
      cycles gave rise to the development of moderate OHSS in the absence of
      exogenously administered human chorionic gonadotrophin, two being conception
      cycles.

PMID- 8300819
TI  - Immunohistochemical sex steroid receptor distribution in endometrium from long
      term subdermal levonorgestrel users and during the normal menstrual cycle.
AB  - The bleeding problems experienced by users of subdermal levonorgestrel implants
      (Norplant) remain unexplained. The aim of the present study was to investigate
      the oestrogen (ER) and progesterone receptor (PR) distribution in levonorgestrel
      treated endometrial biopsies from 31 subjects recruited in Jakarta, Indonesia,
      and to compare the sex steroid receptor immunostaining with that of endometrium
      from 58 normally cycling women from Melbourne, Australia. Sex steroid receptor
      immunoreactivity was additionally compared with days of exposure to subdermal
      levonorgestrel, serum oestradiol and progesterone levels and days of bleeding
      during a 90-day reference period. An immunohistochemical technique with an
      alkaline phosphatase anti-alkaline phosphatase (APAAP) detection system for use
      in formalin-fixed paraffin wax embedded endometrial tissue was employed.
      Significantly greater mean immunostaining scores of stromal PR were observed in
      Norplant compared with control endometrium at all stages across the cycle. No
      significant correlations were demonstrated between sex steroid receptor
      immunostaining and days of exposure to subdermal levonorgestrel, serum oestradiol
      or progesterone concentrations or days of bleeding during a 90-day reference
      period. Whether the elevated stromal PR immunostaining in Norplant-treated
      endometrium is a consequence of increased synthesis or reduced turnover of
      receptor remains unclear. As yet it is undetermined whether increased PR
      immunoreactivity corresponds to an increase in number of functional PR.

PMID- 8300821
TI  - Influence of histocompatibility antigens in recurrent spontaneous abortion and
      its relevance to leukocyte immunotherapy.
AB  - A total of 108 couples with recurrent spontaneous abortion (RSA) were studied to
      investigate the possible influence of histocompatibility antigens (HLA) on their
      condition and its management. HLA-B18 was shown to be at a higher frequency in
      RSA women, but not significantly so after statistical correction. Just over half
      the RSA women shared two or more HLA-A, B or DR antigens with their partners (P <
      0.01), but this group did not differ from the others in clinical or laboratory
      features, nor in subsequent pregnancy success rate. Leukocyte immunotherapy in
      which the donor shared at least one HLA-DR antigen with his partner was not
      associated with a significant improvement in subsequent pregnancy outcome
      compared with HLA-DR mismatched immunotherapy. HLA antibody production following
      leukocyte immunotherapy was influenced by both inoculum size and degree of HLA
      incompatibility, but had no effect on birthweight. Tissue-typing investigations
      are not indicated for individual RSA patients seeking advice or treatment.

PMID- 8300820
TI  - The possible involvement of tissue type plasminogen activator in luteolysis of
      rhesus monkey.
AB  - Changes of plasminogen activators (PA) during different stages of development of
      the corpus luteum, and their possible physiological role in luteolysis were
      studied in rhesus monkeys. It was demonstrated for the first time that monkey
      corpus luteal cells not only produce PA, but that the function of the corpus
      luteum is also closely related to the activity of this enzyme system. Generally,
      the life span for a corpus luteum in monkey is approximately 14-16 days, its
      demise beginning thereafter. In the present study, we found that urokinase in the
      corpus luteum is higher on day 5 and day 10 after human chorionic gonadotrophin
      injection, while the tissue type (t) PA is mainly produced on day 13 when
      luteolysis may take place. Progesterone production remained high on day 5 and day
      10 and decreased dramatically from day 13, indicating the important role of tPA
      but not urokinase (u) PA in suppressing luteal function. When purified tPA (but
      not uPA) monoclonal antibody was added to luteal cell culture to neutralize
      endogenously produced tPA activity, progesterone production in the cells was
      increased significantly. Interestingly, prolactin alone was capable of increasing
      PA production by luteal cells; prolactin together with luteinizing hormone,
      however, had a synergistic luteotrophic effect.

PMID- 8300822
TI  - Avoidance of triplet pregnancies by elective transfer of two good quality
      embryos.
AB  - Attempts to increase the probability of a successful pregnancy in in-vitro
      fertilization (IVF) treatment by increasing the number of embryos transferred
      automatically also increase the probability of multiple pregnancies and their
      attendant risks. Even where the number of transferred embryos is limited to a
      maximum of three as in this and other centres, there is a high incidence of twins
      and triplets. The question therefore arises whether the number of transferred
      embryos should be further limited to a maximum of two in cases where the
      prognosis is otherwise good. The only objection to this idea is a possible
      lowering of pregnancy rate. The present study set out to investigate this
      question. No significant lowering of pregnancy rate was found, so that limiting
      the number of transferred embryos to two where the prognosis is otherwise good
      has now become standard practice in our centre. A good IVF prognosis was defined
      by the following criteria: first attempt for IVF, less than 37 years old, and
      good embryo development. From 183 patients fulfilling these criteria, 80 agreed
      to the transfer of two embryos (group 1) and 103 opted for a triple transfer
      (group 2). Patient characteristics and embryology results were similar in the two
      groups. In group 1, 34 patients (42.5%) became pregnant and in group 2, 50
      (48.5%). This difference is not significant. Similarly, twin pregnancy rates in
      both groups were high; eight twin pregnancies (23.5%) in group 1 and 12 (24%) in
      group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300823
TI  - Investigation of impaired ovarian function as a contributing factor to
      infertility in women with pelvic adhesions.
AB  - A prospective study was performed to determine whether a relationship exists
      between infertility as a result of pelvic adhesions, and raised follicle
      stimulating hormone (FSH). A total of 66 patients, who had a diagnostic
      laparoscopy and dye performed as part of their infertility work-up, had an early
      cycle serum FSH drawn one to two cycles after this procedure. Patients were
      divided into two groups, one with pelvic adhesions as a result of surgery,
      infection or endometriosis, and a control group consisting of those with a normal
      pelvis at laparoscopy or with minimal/mild endometriosis without adhesions. In
      the adhesion group, a correlation was noted between American Fertility Society
      (AFS) adhesion score and basal FSH concentration, although all FSH values for
      this group were within the normal range. This study suggests a correlation
      between pelvic adhesions and ovarian compromise, but a larger study involving
      more severe cases of adhesions is required to determine whether this finding is
      of clinical importance.

PMID- 8300824
TI  - Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male
      infertility.
AB  - Glutathione therapy was used for 2 months in a placebo-controlled double-blind
      cross-over trial of 20 infertile patients with dyspermia associated with
      unilateral varicocele (VAR) or germ-free genital tract inflammation (INF). The
      patients received either glutathione (group 1) or placebo (group 2) for 2 months,
      then they crossed over to the alternative treatment for a further 2 months. The
      patients were randomly and blindly assigned to treatment (one i.m. injection
      every other day of either 600 mg glutathione or an equal volume of a placebo
      preparation). The standard semen analysis and the computer-assisted sperm
      motility analyses were carried out before treatment and during the trial.
      Statistical cross-over analysis, case-control study and treatment efficacy test
      were carried out on groups 1 and 2 and differences in the effects of therapy
      between VAR and INF patients with varicocele or inflammation were tested.
      Glutathione therapy demonstrated a statistically significant positive effect on
      sperm motility, in particular on the percentage of forward motility, the kinetic
      parameters of the computerized analysis and on sperm morphology. The findings of
      this study indicate that glutathione therapy could represent a possible
      therapeutical tool for both of the selected andrological pathologies.

PMID- 8300825
TI  - Analysis of the ability of three probes targeting the outer acrosomal membrane or
      acrosomal contents to detect the acrosome reaction in human spermatozoa.
AB  - A comparative analysis has been undertaken of the behaviour of probes targeting
      the outer acrosomal membrane (Arachis hypogaea lectin) or constituents of the
      acrosomal vesicle (Pisum sativum lectin or monoclonal antibody CRB9) following
      the induction of the acrosome reaction in human spermatozoa with the ionophore
      A23187. The results obtained with these two classes of reagent were highly
      correlated (r = approximately 0.8), although the absolute rates of acrosome
      reaction were significantly different; the probe targeting the outer acrosomal
      membrane (A. hypogaea) consistently gave higher results than either of the probes
      targeting the acrosomal contents. Time-dependent studies, employing a double
      labelling technique, indicated that this difference was apparent from the
      earliest time point examined (15 min after A23187 addition) and reflected the
      more rapid dissipation of the A. hypogaea lectin from the acrosomal region of the
      cell than either of the probes targeting the acrosomal vesicle. These results
      indicate that the outer acrosomal membrane is dispersed from acrosome-reacting
      human spermatozoa more rapidly than certain major constituents of the acrosomal
      vesicle and have possible implications for the design of diagnostic assays
      focusing on this aspect of human sperm function.

PMID- 8300826
TI  - Assessment of human sperm functional changes after in-vitro coincubation with
      cells retrieved from the human female reproductive tract.
AB  - Human spermatozoa must undergo functional changes prior to fertilization;
      however, the site of this physiological event is still unclear. To evaluate the
      influence of the female reproductive tract on sperm fertilizing capacity, fertile
      sperm samples were coincubated with endometrial, oviductal, granulosa and cumulus
      cells, follicular fluid and maternal serum. Sperm penetration into the zona-free
      hamster ova and motion parameters were measured daily for 72 h. Compared to
      control samples, endometrial and oviductal cell cultures did not alter sperm
      fertilizing capacity or their movement characteristics. Sperm coincubated with
      follicular fluid, granulosa or cumulus cells exhibited a significantly higher
      ability to penetrate zona-free hamster ova for up to 48 h. Sperm motility
      increased at 4 h in the presence of follicular fluid and serum. At 24 h sperm
      velocity and amplitude of lateral head displacement significantly declined in
      sperm samples exposed to serum, and velocity also declined in follicular fluid
      and with coincubation using ovarian follicle cells. Sperm motility and velocity
      decreased at 48 h in the presence of serum, follicular fluid, cumulus or
      granulosa cells. Our findings may suggest that specific secretory factors
      produced in the human pre-ovulatory ovarian follicle enhance human sperm
      fertilizing capacity.

PMID- 8300827
TI  - Effect of freezing method, thawing temperature and post-thaw dilution/washing on
      motility (CASA) and morphology characteristics of high-quality human sperm.
AB  - Sixteen semen samples, 12 donor and four patient samples of high initial quality,
      were processed to compare the effect of two freezing methods, two thawing
      temperatures and the effect of dilution and washing on sperm motility and
      morphology characteristics. Sperm samples were divided in two equal parts and
      frozen either by fast vapour freezing or by slow computer-controlled freezing.
      For each freezing method, half of the straws were thawed at room temperature (22
      degrees C), the other half were thawed at 37 degrees C. From each freeze-thawing
      treatment, one straw was evaluated immediately post-thawing; another straw was
      washed to remove the cryoprotectant solution. In this way, each semen sample was
      subjected to eight freeze-thawing treatments. No effect of the freezing method
      and thawing temperature was observed on motility characteristics evaluated by
      computer-assisted semen analysis, nor on light-microscopical morphology
      parameters. Post-thaw dilution and washing, however, exerted a deleterious effect
      on sperm motility, by reducing percentage motility by 50% compared to unwashed
      thawed specimens. Linearity and percentage of morphologically normal spermatozoa
      were obviously impaired, while percentage of abnormal tails and beat cross
      frequency increased significantly. In general, freeze-thawing was most successful
      when rapid vapour freezing was followed by 37 degrees C thawing, and when slower
      computer-controlled freezing was combined with 22 degrees C thawing, causing
      significant interactions between the freezing method and the thawing temperature.
      For semen samples of high initial quality, vapour and computer-controlled
      freezing were equally effective in terms of recovery of morphologically normal,
      motile spermatozoa.

PMID- 8300828
TI  - Comparison between fluorescent peanut agglutinin lectin and GB24 antibody
      techniques for the assessment of acrosomal status.
AB  - In order to compare fluorescent peanut (Arachis hypogaea) agglutinin lectin and
      GB24 antibody (specific for the inner acrosomal membrane) techniques for the
      assessment of acrosome reaction, both methods were applied on semen specimens
      obtained from patients undergoing in-vitro fertilization (IVF). The acrosome
      status was evaluated after a 4 h incubation in B2 medium with and without calcium
      ionophore A23187. Results obtained with both techniques were compared and studied
      as a function of IVF outcome. The percentage of spontaneous acrosome-reacted
      spermatozoa was higher when assessed by lectin than by GB24 (19 +/- 2% versus 11
      +/- 1%; P < 0.001). The difference between the two methods (lectins minus GB24)
      was significantly higher in abnormal than in normal spermatozoa (10 +/- 2% versus
      4 +/- 2%; P < 0.05), but did not significantly correlate with the percentage of
      acrosomes with abnormal morphology (r = 0.28; NS). When studied in relation to
      the IVF results, the response to A23187 was higher in successes than in failures
      (45 +/- 2% versus 34 +/- 4%; P < 0.05) but there was no significant difference
      between methods. Thus the assessment of acrosome reaction is strongly influenced
      by the method used, particularly in abnormal spermatozoa. Since the results
      obtained with lectins were higher in abnormal spermatozoa, GB24 seems to be more
      effective for assessment of true acrosome reaction.

PMID- 8300829
TI  - Sperm aspiration from vas deferens and in-vitro fertilization in cases of non
      treatable anejaculation.
AB  - Spermatozoa were aspirated from the proximal vas deferens of five men with
      persistent anejaculation which could not be overcome by using a vibrator or
      electro-ejaculation. Three men had spinal cord injury, one man had undergone a
      pelvic lymphadenectomy, and in one of them the aetiology was unknown. Fairly good
      numbers of spermatozoa (from 7.5 to 170 million) with progressive motility from
      24 to 75% were obtained from all the eight microsurgically performed aspiration
      attempts. In vitro fertilization (IVF) was successful in seven attempts. Eight
      embryo transfers (six with fresh and two with frozen embryos) resulted in three
      pregnancies. The pregnancy rates, 37% per aspiration and 37% per embryo transfer,
      show that in this small group of patients, aspiration of spermatozoa from the vas
      deferens followed by IVF-embryo transfer is a promising method in the management
      of infertility caused by persistent anejaculation.

PMID- 8300830
TI  - Epididymal sperm aspiration and use of donor spermatozoa when necessary for in
      vitro fertilization, and vasoepididymostomy: an acceptable combination in the
      treatment of obstructive azoospermia.
AB  - Infertility due to obstructive azoospermia in 24 men was treated with a
      combination of scrotal exploration, microsurgical sperm aspiration and
      vasoepididymostomy, at the same operation. In-vitro fertilization (IVF) and
      embryo transfer were performed using epididymal spermatozoa. Donor spermatozoa
      were used if no motile epididymal spermatozoa were obtained. With this
      combination, emotionally and economically acceptable pregnancy rates were
      achieved: 24% per aspiration, 43% per embryo transfer, and 25% per couple. One
      twin pregnancy resulting in the birth of two healthy female infants and one
      ongoing twin pregnancy were achieved with epididymal spermatozoa; four
      pregnancies (one twin, two singletons, one abortion) were achieved with donor
      spermatozoa.

PMID- 8300831
TI  - Variability of human sperm response to immediate and prolonged exposure to
      pentoxifylline.
AB  - Pentoxifylline improves some motility characteristics of human spermatozoa, but
      the variability of response to this drug has not been clearly defined. We used
      computer-assisted sperm motion analysis to examine the in-vitro response of
      spermatozoa to pentoxifylline. Individuals (n = 31) with normal sperm counts were
      randomly selected and their spermatozoa exposed to different concentrations of
      pentoxifylline. Further tests on a subgroup of individuals examined the longevity
      of spermatozoa in response to this agent. Straight line velocity (VSL) was only
      improved at 0.1 mM and the major effect of the drug was on curvilinear velocity
      (VCL) and lateral head displacement (ALH). Prolonged exposure to pentoxifylline
      enhanced sperm motion only at 0.1 mM. Higher concentrations produced dose
      dependent detrimental effects on all the motion characteristics. There was
      considerable inter-individual variability in both VCL and ALH response ranging
      from little or no detectable response to a 40% increase above control value. The
      maximum response was most commonly seen at a concentration of 2 mM
      pentoxifylline.

PMID- 8300832
TI  - Microlaparoscopy: a preliminary report.
AB  - A series of 30 microlaparoscopies performed under local anaesthesia and sedation
      are presented. The visualization of the pelvic organs was acceptable and the
      patients reported mild discomfort only. Microlaparoscopy may potentially replace
      macrolaparoscopy in selected cases.

PMID- 8300834
TI  - Fertility after conservative surgery for adenomyomas.
AB  - Reproductive performance was evaluated after conservative surgery for uterine
      adenomyoma in a prospective, observational study. Twenty-eight women with
      histologically proven adenomyomas had conservative surgery in the period 1985
      1990. Eighteen patients wanting children were regularly followed for a mean +/-
      SD period of 53.2 +/- 23.5 months. Crude and cumulative pregnancy rates were
      calculated after the operation. Thirteen (72.2%) women conceived, for a total of
      18 pregnancies: nine (50%) ended in term deliveries, seven (38.8%) in spontaneous
      abortions, one (5.6%) in ectopic pregnancy and one (5.6%) in a pre-term delivery
      with neonatal death. The cumulative pregnancy rate at 36 months of follow-up was
      74.7%. This analysis of a small series indicates that conservative surgery for
      adenomyomas is associated with a good reproductive prognosis.

PMID- 8300833
TI  - 'Blind' transvaginal gamete intra-fallopian transfer in distal tubal and
      peritubal pathology: an evaluation in respect to the laparoscopic approach.
AB  - Transvaginal gamete intra-Fallopian transfer (GIFT) is a new treatment modality
      for patients with proven tubal patency, avoiding invasive laparoscopy. In this
      study 79 cycles of standard laparoscopic GIFT (group 1) were analysed in
      comparison to 40 cycles of transvaginal intratubal gamete transfer guided by
      tactile sensation (group 2). GIFT in group 1 was performed for standard
      indications; patients with severe intra-abdominal adhesions, distal tubal
      pathology, peritubal adhesions or extreme obesity were included in group 2. No
      difference in mean age, duration of infertility, oestradiol level and number of
      oocytes was found. In group 1 a clinical pregnancy rate of 33% per GIFT cycle (n
      = 79) was achieved. The clinical pregnancy rate in group 2 was 17.5% per gamete
      transfer cycle. In conclusion, transvaginal GIFT offers an acceptable chance for
      in-vivo fertilization to patients who cannot be treated laparoscopically despite
      having patent tubes and who refuse in-vitro fertilization.

PMID- 8300835
TI  - Diagnosis and treatment of proximal tubal obstruction by fluoroscopic
      transcervical fallopian tube catheterization.
AB  - The efficacy of fluoroscopic transcervical Fallopian tube catheterization in
      treating patients with proximal tubal obstruction was investigated. In 11 (15.9%)
      of the 69 patients who entered the study, patency of the proximal Fallopian tubes
      was shown by a pre-treatment hysterosalpingogram or an ostial selective
      salpingogram. Transcervical Fallopian tube catheterization attested to the
      success of recanalization in at least one of the obstructed tubes in 41 of our 58
      patients (70.7%). Of 92 obstructed tubes, 56 (60.9%) were successfully
      recanalized. However, normal tubal visualization was possible in only 13 tubes
      (23.2%). Most of the recanalized tubes were considered to be peritubal adhesions
      (64.3%). Eight of 36 (22.2%) patients who had been successfully recanalized
      achieved pregnancies; 12 patients demonstrated normally appearing salpingograms
      after the procedure, and five (41.7%) had an intra-uterine pregnancy. Suspected
      peritubal adhesions were exhibited on post-operative salpingograms of 24
      patients, one of whom had an intra-uterine pregnancy, while two had tubal
      pregnancies. Transcervical Fallopian tube catheterization is a simple and
      effective method for evaluating and treating proximal tubal obstruction. Most of
      the patients (70.7%) in whom recanalization was successful showed significant
      signs of distal tubal damage. This procedure can also be used to arrive at a
      prognosis regarding conception.

PMID- 8300836
TI  - Colour Doppler ultrasound guidance for transcervical wire tuboplasty.
AB  - To evaluate the usefulness of high-resolution ultrasound with colour Doppler
      mapping system in performing transcervical wire tuboplasty, 13 infertile women
      with bilateral proximal tubal obstruction demonstrated by X-ray or colour Doppler
      ultrasound hysterosalpingography and chromoperturbation at laparoscopy were
      treated by transcervical wire tuboplasty utilizing colour Doppler mapping
      ultrasound guidance. A co-axial catheter was used to introduce a 0.016-in.
      flexible wire to the occluded portion. Transcervical wire catheterization was
      accomplished in 25 of 26 tubes (96%), resulting in patency in 24 of 25 tubes
      (96%). At the end of the procedure all patients had at least one tube patent
      (100%). Five (38%) women achieved pregnancies within 1 year after the procedure.
      High-resolution ultrasound with colour Doppler mapping system is an efficacious
      way to perform transcervical wire tuboplasty, avoiding the risk of radiation and
      allergic reaction.

PMID- 8300837
TI  - The applicability of the cumulative embryo score system for embryo selection and
      quality control in an in-vitro fertilization/embryo transfer programme.
AB  - The cumulative embryo score system involves three aspects of relevance in
      pregnancy achievement during in-vitro fertilization (IVF) and embryo transfer:
      cleavage rates, morphological qualities and the number of embryos transferred.
      The scores of 602 IVF/embryo transfer trials were calculated and analysed to
      determine the system's relationship to pregnancy rate, pregnancy outcome and the
      incidence of twin and triplet pregnancies. The system was also applied to cycles
      where endotoxins were either present in or absent from culture medium, in order
      to evaluate its validity in quality control analyses. Pregnancy rates were found
      to increase from 4%, with scores between 1 and 10, to 35% in the 41-50 group. The
      score of 20 was the criterion for separating patients into poor and good
      pregnancy prognosis groups (P = 0.00001). Biochemical abortions occurred more
      frequently with scores < 20 (P = 0.00978), but a similar relationship was not
      found in clinical abortion rates (P = 0.62206). Birth rates below and above a
      score of 20 (2.8 and 19.2%, respectively) differed significantly (P = 0.0005).
      The scores of twins overlapped extensively with those of singleton births, but
      those of all triplets were > 40. The system did not reflect a correlation between
      embryo quality and the presence of endotoxins in culture medium.

PMID- 8300838
TI  - Microsurgical correction of partially degenerate mouse embryos promotes hatching
      and restores their viability.
AB  - We have evaluated the effects of degeneration of blastomeres on the developmental
      fate of mouse embryos. Micromanipulation techniques were used first to destroy
      one or two blastomeres of a 4-cell embryo (thereby creating three-quarter and
      half embryos), and later to repair the anomaly by removing the degenerate
      material. The embryos were either cultured in protein-free or protein
      supplemented medium. When cultured in protein-supplemented medium, three-quarter
      embryos hatched at the same rate as intact embryos (84 and 91%, respectively),
      but this rate was reduced (54%; 67/125) when the embryos were cultured in a
      protein-free environment. Destruction of two blastomeres of a 4-cell embryo and
      culture in protein-free medium was detrimental, as only 3.2% (4/124) hatched. By
      supplementing the culture medium with protein, some of these half embryos were
      rescued, as shown by a 34% (32/95) hatching rate. A more dramatic increase in
      hatching was achieved, however, after repair of the half embryos by microsurgical
      removal of the degenerate material. In this case, 72% (78/109) of the repaired
      embryos were able to hatch. These findings may have implications for human in
      vitro fertilization where partial embryonic degeneration or fragmentation often
      leads to embryonic demise and reduced implantation. Moreover, these observations
      may provide important clues to mechanisms of mammalian embryonic hatching.

PMID- 8300839
TI  - Gender preselection in humans? Flow cytometric separation of X and Y spermatozoa
      for the prevention of X-linked diseases.
AB  - Human X- and Y-chromosome-bearing spermatozoa were separated based on their DNA
      content, using modified flow cytometric cell sorting technology. The resulting
      separation purity of the X-bearing from Y-bearing spermatozoa was evaluated using
      in-situ hybridization with alpha satellite DNA probes for the X- and Y
      chromosomes. In the putative X-enriched-sorted populations, an average of 82% of
      the spermatozoa showed a hybridization signal with the X probe. Similarly, in the
      Y-sorted population 75% gave a signal with the Y probe. Sorted X- and Y-bearing
      spermatozoa were found to maintain their viability for several hours after
      sorting. These results demonstrate that the human sperm sex ratio can be
      significantly shifted to favour the selection of female-producing (X) spermatozoa
      or male-producing (Y) spermatozoa when spermatozoa are flow cytometrically sorted
      on the basis of DNA content. We propose that flow cytometrically sorted human
      spermatozoa, used in conjunction with in-vitro fertilization or intra-oviductal
      insemination, could be used by families who are at risk for X-linked diseases to
      preferentially produce female offspring. Sorted spermatozoa could also be used to
      pre-select for male offspring if that were medically indicated.

PMID- 8300840
TI  - The abortifacient effect of misoprostol in the second trimester. A randomized
      comparison with gemeprost in patients pre-treated with mifepristone (RU486).
AB  - The objective of this work was to study the abortifacient effects of misoprostol,
      an orally active prostaglandin E1 (PGE1) analogue, in the second trimester. A
      randomized study of two prostaglandin regimens in women pre-treated with the
      antiprogesterone mifepristone was carried out in the gynaecological wards of
      Aberdeen Royal Hospitals, NHS Trust, and included 60 women at 13-20 weeks'
      gestation, in whom termination of pregnancy had been agreed. Following pre
      treatment with mifepristone 600 mg women were randomly allocated to one of two
      prostaglandin regimens which started 36-48 h later. The first misoprostol 400
      micrograms orally (up to three doses) followed by gemeprost vaginal pessary 1 mg
      up to two doses. The second was gemeprost vaginal pessary 1 mg up to five doses.
      The main outcome measures were success rate induction-to-abortion interval and
      side-effects. There were no significant differences between the two groups in any
      of the main outcome measures. We conclude that misoprostol is a stable, cheap
      PGE1 analogue with demonstrable efficacy and acceptable side-effects in the
      management of second trimester abortion. Further work is needed to establish the
      optimum dose and regimen.

PMID- 8300841
TI  - Exercise and gonadal function.
AB  - Exercise is associated with release of a number of pituitary and hypothalamic
      hormones and a decline in the concentration of luteinizing hormone (LH). Follicle
      stimulating hormone (FSH) is generally not influenced by exercise. Serum inhibin
      concentrations, which are reciprocally influenced by serum FSH concentrations,
      are increased in some animals but are unchanged after acute exercise in human
      males. Teleologically, the decline in gonadotrophic hormone (LH) secretion after
      exercise may be geared to enhance individual survival over species propagation in
      times of stress, analogous to the postulated 'fight or flight' reaction. The
      decrease in gonadotrophic hormone (LH) secretion is believed to be due to changes
      in gonadotrophin releasing hormone (GnRH) pulse frequency and amplitude,
      particularly in women, who often develop amenorrhoea. Males have less dramatic
      changes in their hypothalamic-pituitary-gonadal axis, although a significant
      decrease in serum testosterone in physically conditioned males can usually be
      demonstrated. In this update possible mechanisms for the decline in gonadotrophin
      secretion with exercise are briefly discussed.

PMID- 8300842
TI  - Involvement of leukocytes and cytokines in the ovulatory process and corpus
      luteum function.
AB  - The role of leukocytes and cytokines in ovarian physiology is now established,
      although the function of each cell type and cytokine remains to be determined in
      detail. Current knowledge of these effects on follicle development, ovulation,
      luteinization and luteotrophic process and luteolysis is reviewed. It is possible
      that further research will help to unravel some of the clinical mysteries in
      ovarian function, including polycystic ovary syndrome, premature menopause,
      ovulatory disorders, and luteal phase defect. Furthermore, the increasing use of
      cytokines and their antagonists in clinical practice may have significant effects
      upon reproductive function.

PMID- 8300843
TI  - X-ray diffraction study on mammalian visceral smooth muscles in resting and
      activated states.
AB  - Structural changes of guinea pig taenia coli and rat anococcygeus muscle during
      contraction were studied by X-ray diffraction. The diffraction pattern of the
      taenia coli showed the 14.4-nm myosin reflection, the 5.9-nm actin layer-line and
      a diffuse equatorial peak at 1/11.4 nm-1. On application of carbachol, the muscle
      contracted and the intensity of the 14.4-nm reflection showed a concentration
      dependent decrease: the maximum decrease was 24% at 2 x 10(-5) M. Such an
      intensity decrease was not observed in K-contracture (154 mM). The intensity of
      the 5.9-nm actin layer-line did not change appreciably on activation. The
      equatorial peak became broader during contraction. The 14.4-nm myosin reflection
      of the anococcygeus muscle was weak. Its intensity increased by 106% during
      contraction induced by 2 x 10(-5) M phenylephrine and by 75% during K
      contracture. These results suggest that the number of myosin filaments may
      increase during contraction of rat anococcygeus muscle but not guinea pig taenia
      coli.

PMID- 8300844
TI  - Synthesis of non-nucleotide ATP analogues and characterization of their
      chemomechanical interaction with muscle fibres.
AB  - To probe the substrate requirements for the actomyosin chemomechanical
      interaction, the effects of a series of eight new non-nucleotide ATP analogues on
      actomyosin-catalysed hydrolysis rates and on fibre mechanics have been
      investigated. These analogues have substitutions of new functional groups at the
      2- and 4-positions of the ATP analogues, 2-[(4-azido-2-nitrophenyl)amino]ethyl
      triphosphate (NANTP), and 3-[(4-nitrophenyl)amino]propyl triphosphate (PrNANTP).
      Previous work has shown NANTP but not PrNANTP will support active tension and
      shortening in skinned muscle fibres in a manner almost identical to ATP. Here all
      2- and 4-phenyl substituted analogues had myosin subfragment 1 (S1) NTPase
      hydrolysis rates higher than ATP and the rates were stimulated by addition of
      actin. In general, the replacement of the 4-azido group of NANTP with -H, -NO2 or
      -NH2 had small effects on fibre mechanics while replacement of 2-NO2 group with 
      H or -NH2 dramatically lowered the ability of the new analogues to support active
      tension and shortening. All PrNANTP-based analogues were ineffective in
      supporting active tension or shortening. We found no correlation between S1 or
      actoS1 NTPase rates and any mechanical parameters. However, for all analogues
      there was a strong correlation between the maximal velocity of shortening (Vmax)
      and isometric tension (P0). A three-state, chemomechanical model is proposed in
      which the analogues effect the transition rate into a strongly-bound, force
      producing crossbridge state to account for this correlation. These studies
      identify 2-[(2-nitrophenyl)amino]ethyl triphosphate as the chemically simplest
      ATP analogue which closely mimics the effect of ATP in skinned muscle fibres.

PMID- 8300845
TI  - Active tension generation in isolated skeletal myofibrils.
AB  - Single or double myofibrils isolated from rabbit psoas muscle were suspended
      between a fine needle and an optical force transducer. By using a photodiode
      array, the length of every sarcomere along the specimen could be measured.
      Relaxed specimens exhibited uniform sarcomere lengths and their passive length
      tension curve was comparable to that of larger specimens. Most specimens could be
      activated and relaxed four to five times before active force levels began to
      decline; some specimens lasted for 10-15 activation cycles. Active tension (20-22
      degrees C) was reproducible from contraction to contraction. The contractile
      response was dependent on initial sarcomere length. If initially activated at
      sarcomere lengths of > or = 2.7 microns, one group of sarcomeres usually
      shortened to sarcomere lengths of 1.8-2.0 microns, while the remaining sarcomeres
      were stretched to longer lengths. Myofibrils that were carefully activated at
      shorter initial sarcomere lengths usually contracted homogeneously. Both
      homogeneous and inhomogeneous contractions produced high levels of active
      tension. Calcium sensitivity was found to be comparable to that in larger
      preparations; myofibrils immersed in pCa 6.0 solution generated 30% of maximal
      tension, while pCa 5.5-4.5 resulted in full activation. Active tension at full
      overlap of thick and thin filaments ranged from 0.34 to 0.94 N mm-2 (mean of 0.59
      N mm-2 +/- 0.13 SD. n = 65). Even allowing for a maximum of 20% nonmyofibrillar
      space in skinned or intact muscle fibres, the mean tension generated by isolated
      myofibrils per cross-sectional area is higher than by fibre preparations.

PMID- 8300846
TI  - Distribution of connectin (titin), nebulin and alpha-actinin at myotendinous
      junctions of chicken pectoralis muscles: an immunofluorescence and immunoelectron
      microscopic study.
AB  - The distribution of connectin (titin), nebulin and alpha-actinin in the areas of
      myotendinous junctions of chicken pectoralis muscles was examined by
      immunocytochemical methods. Staining with antibodies against connectin (4C9, SM1
      and P1200) and nebulin formed 'doublets' flanking nonterminal Z-bands; near the
      end of muscle fibres 'singlets' were seen within the terminal sarcomere on the
      side adjacent to the terminal Z-bands. The apical regions of muscle processes,
      where no myosin filaments are present although actin filaments exist, were
      reactive with anti-nebulin but not with anti-connectin. Antibodies against
      pectoralis (skeletal muscle type) alpha-actinin stained non terminal Z-bands and
      that against gizzard (smooth muscle type) the sarcolemma. Terminal Z-bands were
      unreactive with both of these antibodies. These findings indicate that, although
      terminal and nonterminal Z-bands differ in their molecular composition, connectin
      and nebulin filaments appear to link myosin and actin filaments, respectively, to
      both Z-band types.

PMID- 8300847
TI  - Relation between work and power calculated from force-velocity curves to that
      done during oscillatory work.
AB  - The force-velocity relation during oscillatory work was compared with that
      measured in the traditional way with quick release and force clamps using toad
      sartorius, frog sartorius, and mouse soleus muscles. Plotting the force and
      corresponding velocity data in this way produces a 'power-loop'. The 'power-loop'
      has less intuitive value than the frequently reported 'work-loops' but it is
      useful because it permits comparison with the force-velocity curve produced using
      traditional methods. The force/velocity combinations for oscillatory work during
      a contraction often exceed those that would be predicted from the force-velocity
      curve. Although it has been known for many years that more force is developed by
      stimulated muscle when it is being stretched than can be developed during an
      isometric contraction, my results show that the increase in force is of
      importance at stretch velocities that probably occur in vivo during locomotion.

PMID- 8300848
TI  - Non-homogeneous Ca release in isolated frog skeletal muscle fibres.
AB  - We have examined the spatial distribution of [Ca2+]i during tetanic stimulation
      in frog skeletal muscle cells using a fluorescence imaging method. We have found
      a completely unexpected pattern of Ca release: Ca is released forming gradients
      composed of spots of very significant and slow fluctuations of calcium release.
      Our findings could be explained if the calcium release process in skeletal muscle
      is influenced significantly by [Ca2+]i, such as in cardiac muscle, and suggests
      that the SR/Ca release control can include the established voltage-dependent plus
      a cardiac-like process of calcium-induced Ca release and a Ca release inhibition
      by Ca.

PMID- 8300849
TI  - Fish muscle structure: fibre types in flatfish and mullet fin muscles using
      histochemistry and antimyosin antibody labelling.
AB  - In studies of the myosin crossbridge interaction with actin in vertebrate
      muscles, the muscles of bony fish have the unique advantage for ultrastructural
      work that the A-band has a simple 'crystalline' lattice of myosin filaments.
      However, the anatomy and physiology of these fish muscles is relatively poorly
      understood compared with the rabbit, chicken or frog muscles conventionally used
      for crossbridge studies. Here the fibre types in fish fin muscles have been
      characterized to allow sensible selection of single fish fibres for
      ultrastructural studies. The fibre type compositions of the fin muscles of
      mullet, plaice, sole and turbot were examined by histochemistry and
      immunohistochemistry using polyclonal antibodies raised against various myosin
      isoforms: fish slow, fish fast, mammalian fast (type IIA) and chicken tonic
      myosins. In the mullet, fin muscles were composed of variable proportions of fast
      and slow fibres. In the three flatfish, the fin muscle showed a zonal arrangement
      with slow fibres, binding anti-slow myosin antibody, next to the skin (alpha
      region). The bulk of the muscle, distal to the skin, was a typical fast muscle
      both histochemically and in its reaction with antibodies (delta region). Between
      these two regions there may be one (sole) or two (turbot, plaice) intermediate
      zones (beta and gamma regions) comparable to the pink/intermediate layer of
      myotomal muscle. In the plaice fin muscle, two kinds of slow fibre could be
      distinguished immunohistochemically.

PMID- 8300850
TI  - Examined the activation of central myofibrils during muscle fatigue caused by
      repeated short tetani.

PMID- 8300851
TI  - Regulation of monocyte chemoattractant protein-1 expression in adult human non
      neoplastic astrocytes is sensitive to tumor necrosis factor (TNF) or antibody to
      the 55-kDa TNF receptor.
AB  - Infiltration of the central nervous system (CNS) by monocytes is a characteristic
      of many non-malignant disease processes, although the signals regulating such
      traffic are unclear. Tumor necrosis factor (TNF) and other inflammatory cytokines
      have been shown to elicit production of monocyte chemoattractant activity in
      glioma cells, but the regulation of such activity in non-neoplastic adult
      astrocytes has not been examined. We previously observed that TNF constituted a
      proliferative signal for non-neoplastic adult human astrocytes in vitro involving
      the 55-kDa TNF receptor. In the present study, we demonstrate that TNF exposure
      enhances the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and
      functional monocyte chemoattractant activity in non-neoplastic astrocytes.
      Results indicated that MCP-1 mRNA expression was maximal within 3 h, and was
      further augmented by the protein synthesis inhibitor cycloheximide (CY). Antibody
      (htr-9) directed against the 55-kDa TNF receptor also elicited MCP-1 mRNA
      expression while antibody to the 75-kDa TNF receptor (utr-1) was ineffective.
      Secretion of monocyte chemoattractant activity was significantly greater in TNF-
      or htr-9-treated astrocytes than in utr-1-treated or untreated controls; activity
      was abolished by treatment with antibody to MCP-1. These findings suggest that
      non-neoplastic adult human astrocytes may contribute to CNS inflammatory
      responses by mediating recruitment of peripheral blood monocytes.

PMID- 8300853
TI  - Cytokine induction of heat shock protein expression in human oligodendrocytes: an
      interleukin-1-mediated mechanism.
AB  - In this study, we examined the role of cytokines, known to be in elevated levels
      in multiple sclerosis (MS) plaques, in regulating oligodendrocyte (ODC)
      expression of heat shock protein (hsp) in human brain-derived glial cell
      cultures. Using dual-stain immunohistochemistry, we initially compared the
      ability of a mixture of cytokines (IL-1 alpha, IL-1 beta, IL-2, IL-6, IL-8, TNF
      alpha, TNF-beta, IFN-beta and IFN-gamma) with that of physical stimuli such as
      heat shock and peroxide, to increase cellular expression of the mainly inducible
      hsp72 species in mixed glial cell cultures (containing ODC, astrocytes and
      microglia). Similar to heat shock and peroxide, the cytokine mixture induced
      hsp72 expression only in ODC (70 +/- 5% vs. a baseline of 3 +/- 1% positive
      cells). When used individually, however, only IL-1 alpha (79 +/- 3%), IFN-gamma
      (70 +/- 2%) and TNF-alpha (65 +/- 5%) induced ODC hsp72 expression in mixed glial
      cell cultures. In purified ODC preparations, only IL-1 alpha induced hsp72
      expression (84 +/- 4%). An IL-1 receptor antagonist (IL-1ra), abrogated hsp72
      induction by IL-1 alpha (16 +/- 3%) as well as that due to IFN-gamma (14 +/- 1%)
      and TNF-alpha (13 +/- 2%) in mixed glial cell cultures. Furthermore, ODC express
      IL-1 receptors, detected by confocal laser scanning microscopy. Our data indicate
      that cytokines mediate hsp induction in ODC possibly via a final common pathway
      involving IL-1 binding to its receptor on ODC. Such interaction could enhance any
      putative ODC-immune interactions which are dependent on hsp molecule recognition.

PMID- 8300852
TI  - Role of arcuate nucleus of the hypothalamus in the acquisition of association
      memory between the CS and US.
AB  - A single trial association protocol was used to demonstrate a conditioned
      increase in natural killer (NK) cell activity. The signals used were odor of
      camphor as the conditioned stimulus (CS) and polyinosinic-polycytidylic acid
      (poly I:C) as the unconditioned stimulus (US). This model has been used to
      dissect the underlying mechanisms of interaction between the central nervous
      system (CNS) and the immune system (IS) and vice versa. Here, we demonstrate the
      potential role played by the arcuate nucleus of the hypothalamus in the
      acquisition of association memory between the CS and the US. Chemical destruction
      of the arcuate nucleus with monosodium glutamate (MSG) was used for this purpose.
      Mice with arcuate nucleus lesion prior to the association protocol did not
      demonstrate a conditioned increase in NK cell activity. However, the lesion has
      no effect if produced prior to exposure to the CS at recall. These studies
      demonstrate the significant role played by the hypothalamus (arcuate nucleus) in
      a conditioned response.

PMID- 8300854
TI  - Up-regulation of lipocortin-1 and its mRNA in reactive astrocytes in kainate
      lesioned rat cerebellum.
AB  - We have used a combined molecular and immunocytochemical approach to examine the
      expression of lipocortin-1 (LC-1) in kainate-lesioned rat cerebellum. Using
      immunocytochemistry, Western and Northern blotting, we have shown upregulation of
      LC-1 mRNA and expression of LC-1 localised specifically to reactive astrocytes.
      These studies suggest that reactive astrocytes are a major synthetic compartment
      for the expression of LC-1. The well-reported immuno-suppressive effects of
      lipocortin(s), suggests that reactive astrocytes could serve to negatively
      modulate inflammatory reactions in the central nervous system.

PMID- 8300855
TI  - Effects of phenytoin administration on murine immune function.
AB  - The results obtained in these series of experiments indicate that oral
      administration of phenytoin (100, 50, or 25 mg/kg) to mice significantly
      depressed both humoral and cellular immune responses, evaluated by the techniques
      of enumeration of direct and indirect spleen plaque-forming cells (PFC) and the
      delayed-type hypersensitivity reaction (DTH) against sheep red blood cells (SR
      BC), when compared with those observed in normal control animals. Furthermore,
      spleen cells, purified splenic T lymphocytes or Ly 2 + T cells obtained from 100
      mg/kg phenytoin-treated donor mice were capable of diminishing both PFC and DTH
      responses of normal cells transferred into lethally irradiated mice. The
      immunodepressor effect of phenytoin was observed despite the fact that
      administration of this drug induced a rise in spleen cellularity.

PMID- 8300856
TI  - Oral administration of the oxidant-scavenger N-acetyl-L-cysteine inhibits acute
      experimental autoimmune encephalomyelitis.
AB  - The prevention of acute experimental autoimmune encephalomyelitis (EAE) by N
      acetyl-L-cysteine (NAC), a potent free radical scavenger, is described.
      Administrated ad libitum to SJL/J mice at a dosage of 0.2-2 mg/ml in drinking
      water from the day of the encephalitogenic injection, the agent significantly
      inhibited the induction of acute EAE. The improvement in clinical condition was
      dose-dependent. A complete protective effect required administration of the agent
      at an early stage. Examination of lymphocytes from NAC-treated EAE mice showed
      that at early stages (days 9 and 15) post encephalitogenic injection the anti
      oxidant enhanced the specific lymphocyte proliferative response to the immunizing
      antigens. Examination of the mitogenic stimulation of lymphocytes from naive
      animals in the presence of NAC in vitro indicated that the scavenger enhanced the
      stimulative effect of LPS in a dose-dependent manner. The immunomodulative
      capacity of the anti-oxidant NAC suggests that free radicals are involved in the
      pathogenesis of acute EAE.

PMID- 8300857
TI  - Immunological effects of acute and chronic nicotine administration in rats.
AB  - We previously demonstrated that acute nicotine administration decreased the
      response of rat blood leukocytes (PBL) to concanavalin A (ConA). We now extend
      those findings to a comparison between the effects of acute and prolonged
      nicotine exposure (ten daily injections), on PBL and splenocytes (SL). A single
      injection suppressed the PBL response to ConA and phytohemagglutinin (PHA);
      tolerance developed by ten injections. In contrast, acute nicotine did not affect
      SL response to ConA and reduced the PHA response only at the highest
      concentration. Ten nicotine injections enhanced SL responsiveness to PHA. The
      only change in PBL subsets was an increase in CD8+ cells following ten
      injections.

PMID- 8300858
TI  - Evidence for the involvement of macrophage-derived nitric oxide in the modulation
      of immune status by a conditioned aversive stimulus.
AB  - Prior work in our laboratory has demonstrated that exposure to a conditioned
      aversive stimulus developed through pairings with electric shock results in
      pronounced alterations of immune status. These conditioned alterations of immune
      status include a decreased in natural killer cell activity, decreased production
      of interleukin-2 and gamma-interferon by concanavalin A (ConA)-stimulated
      splenocytes and a profound suppression of the mitogenic responsiveness of T and B
      lymphocytes to mitogens. The present study examines the role of macrophage
      derived nitric oxide in the conditioned stimulus-induced suppression of
      lymphocyte proliferation by measuring the level of nitrite accumulation in
      culture, determining the effect of macrophage depletion, and assessing the effect
      of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of the L-arginine
      dependent nitric-oxide synthesizing pathway, alone and in combination with L- or
      D-arginine. The results show that the conditioned suppression of the mitogenic
      responsiveness of splenocytes to ConA is accompanied by a marked increase in
      nitrite accumulation. Both the depletion of macrophages and the addition of L
      NMMA attenuates the conditioned suppression of ConA-stimulated lymphocyte
      proliferation. Furthermore, the addition of excess L-arginine, but not D
      arginine, counteracts the effect of L-NMMA. The present findings show that the
      neuroendocrine alterations induced by a conditioned aversive stimulus suppress
      lymphocyte proliferation through alteration of the production of nitric oxide by
      macrophages.

PMID- 8300859
TI  - Beta-endorphin modulates calcium channel activity in human neutrophils.
AB  - 10(-6) M n-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated Ca2+ flux in
      human neutrophils is characterized by a profile composed of two peaks of
      different amplitude and breadth. beta-Endorphin inhibited the magnitude and
      modulated the kinetics of the second peak in a manner which was dose-dependent
      and could reflect either negative cooperativity or heterogeneity of binding
      sites. The second peak arises from calcium channel activity since in the presence
      of nifedipine or EGTA it was not evident while the first peak was reduced about
      24%. Similarly, at 15 degrees C, where we were unable to detect any channel
      activity, the first peak was diminished by 35% and beta-endorphin had no
      detectable effect on this peak. These results led us to conclude that the first
      peak is chiefly composed of Ca2+ recruited from cytosolic stores which are
      relatively insensitive to the above treatments and a smaller fraction of calcium
      originating in calcium channel activity. Hence, we reason that beta-endorphin
      modulates only the calcium ion flux arising from calcium channel function.

PMID- 8300860
TI  - Expression of VIP receptors in mouse peritoneal macrophages: functional and
      molecular characterization.
AB  - Receptors for VIP in mouse peritoneal macrophages (MPM) were examined using
      [125I]labeled VIP as ligand. The receptor binding was rapid, reversible,
      saturable, specific, and dependent on time, pH, temperature and cell
      concentration. At 15 degrees C, the stoichiometric data suggested the presence of
      two classes of VIP receptors with Kd values of 1.05 +/- 0.2 and 66.4 +/- 11.0 nM
      and binding capacities of 19.2 +/- 2.8 and 706.6 +/- 172.0 fmol VIP/10(6) cells.
      The interaction showed a high degree of specificity, as suggested by competition
      experiments with various peptides structurally related to VIP as follows: VIP >
      helodermin > rGRF > PHI >> secretin. Glucagon, pancreastatin, somatostatin,
      insulin, and octapeptide of cholecystokinin (CCK 26-33) were ineffective at
      concentrations as high as 1 microM. VIP was a potent and efficient stimulator of
      cyclic AMP production in MPM. The stimulation was observed at a concentration as
      low as 0.01 nM VIP. Half-maximal stimulation (ED50) was observed at 1.0 +/- 0.2
      nM VIP, and maximal stimulation (three-fold above basal levels) was obtained
      between 0.1-1 microM. The cyclic AMP system of mouse peritoneal macrophages
      showed a high specificity for VIP. The order of potency observed in inducing
      cyclic AMP production was VIP > helodermin > rGRF > PHI >> secretin. Glucagon,
      insulin, pancreastatin, somatostatin and octapeptide of cholecystokinin did not
      modify cyclic AMP levels at concentrations as high as 1 microM.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8300861
TI  - Inflammation after axonal injury has conflicting consequences for recovery of
      function: rescue of spared axons is impaired but regeneration is supported.
AB  - Neural injury leads to tissue damage beyond that caused by the initial lesion,
      mainly as a result of a chain of autodestructive events triggered by the trauma.
      These events apparently include the activation of immune-derived cells and their
      products, as treatment with anti-inflammatory agents, such as corticosteroids,
      limits the damage and thus improves recovery. On the other hand, immune-derived
      substances, such as cytokines, are thought to play an important role in post
      traumatic axonal regeneration. Thus, the need to reduce inflammation to limit the
      spread of damage appears to be in conflict with the need to permit inflammation
      to promote regeneration. Comprehension and resolution of this apparent conflict
      may lead to the development of treatment protocols aimed at rescuing axons spared
      by the initial injury, without hampering the potential regeneration of directly
      and indirectly injured axons. In this study, carried out on rats with crushed
      optic nerves, daily intraperitoneal injections of dexamethasone commencing prior
      to the injury significantly attenuated the injury-induced decrease in
      electrophysiological activity and reduced the area of tissue damage. On the other
      hand, dexamethasone treatment reduced the permissiveness of the injured nerves to
      neural adhesion and regrowth in vitro. This latter phenomenon was also observed
      in injured peripheral nerves. Results are discussed with respect to the possible
      establishment of an appropriate protocol for corticosteroid treatment of nerve
      injuries aimed at promoting neuronal rescue without compromising neuronal
      regeneration.

PMID- 8300862
TI  - The HLA-Dw2 haplotype segregates closely with multiple sclerosis in multiplex
      families.
AB  - Multiple sclerosis (MS) is associated with the HLA class II specificity Dw2, but
      the importance of its influence has been questioned, since sib-pair analysis has
      failed to show linkage with this haplotype. However, the use of 'identity by
      descent' (IBD) analysis may not be ideal, since it does not make use of the facts
      that (i) the Dw2-haplotype is the only haplotype with a confirmed role in MS, and
      (ii) it performs its influence in a dominant manner. We have investigated nine
      Swedish multiplex MS families. In eight of the families, the Dw2 haplotype
      occurred in MS patients. Within these families, Dw2 was shared by all 17
      individuals with MS. In a compilation of 48 published multiplex MS families in
      which at least one patient carried Dw2, only three of 107 individuals with MS did
      not carry the Dw2 haplotype. This indicates that the Dw2 haplotype, when present
      in familial MS, may confer a stronger influence in MS susceptibility than
      generally recognized.

PMID- 8300863
TI  - Exploring the sociotropy-autonomy dimensions in a sample of Turkish psychiatric
      inpatients.
AB  - The present study explored the constructs of sociotropy and autonomy with a group
      of Turkish depressed inpatients, who were administered the Beck Depression
      Inventory, the Dysfunctional Attitudes Scale, the Automatic Thoughts
      Questionnaire, and the Sociotropy-Autonomy Scale. A comparison group of students
      from three SES levels also were included in the study. Comparisons were made on
      the scale scores among the non-dysphoric students, the dysphoric students, and
      the depressed patients. The results seem to support the relationship of
      sociotropy with other depression measures in both samples. However, several
      problems were encountered with the construct autonomy as it is conceptualized in
      the Sociotropy-Autonomy Scale.

PMID- 8300864
TI  - Developmental and gender differences in the relationship of behavior pattern to
      heart rate reactivity between two teenage samples.
AB  - The Type A Behavior Pattern was assessed for 122 teenagers from two age-groups.
      Subjects had their heart rate measured during rest and presentation of a mental
      arithmetic stressor under timed and competitive conditions. Data were analyzed to
      determine whether sex, age, task performance, and behavior pattern predicted the
      degree of heart rate reactivity shown by these children. Although there were no
      significant main effects for behavior pattern, sex, or age, there was a
      significant interaction among age, sex, and behavior pattern. It is suggested
      that the two age groups of teenagers sampled here differ in the relationships
      they show between behavior pattern and heart rate reactivity. This result
      challenges some previous assumptions with regard to the homogeneity of teenagers
      on this issue.

PMID- 8300865
TI  - Depression and assessment of intellectual functioning.
AB  - This study examined the relation between WAIS and Wilson predictor of premorbid
      intelligence scores of 27 depressed and 34 nondepressed psychiatric patients. No
      significant difference was found between the WAIS and Wilson predictor of
      premorbid intelligence scores nor between the Verbal and Performance IQs.

PMID- 8300866
TI  - Effects of behavioral stimuli on plasma interleukin-1 activity in humans at rest.
AB  - Interleukin-1 (IL-1) bioassays were done on 208 serum samples drawn from 7
      volunteers, over several hours at 5-minute intervals, before, during, and after a
      relaxation-related behavioral stimulus. Individuals showed up to a 267% increase
      (t[29] = 7.750, p = 1 x 10(-7).) in IL-1, and for the group, a mean 48.1%
      elevation (t[5] = 4.128, p = .003) occurred, during the stimulus interval
      relative to baseline. When baselines were repeated, IL-1 activity rapidly
      returned toward baseline values. Suggestions to picture one's immune cells
      fighting illness appeared to have no uniform effect for all subjects. Such rapid
      changes in plasma IL-1, concomitant with stimuli, indicate a new way to alter
      immune function and further understand disease susceptibility.

PMID- 8300867
TI  - The VCOP Scale: a measure of overprotection in parents of physically vulnerable
      children.
AB  - A scale is developed for measuring the overprotecting vs. optimal developmental
      stimulation tendencies for parents of physically "vulnerable" children. A series
      of items were administered to parents whose parenting techniques had been rated
      as either highly overprotective or as optimal by a group of MDs and other
      professionals. Correlations were estimated between each of the items and parental
      tendencies as rated by professionals. Twenty-eight items were selected that
      provided maximum prediction of over-protection. The resulting R2 was
      extraordinarily high (.94). Coefficient alpha and test-retest coefficients were
      acceptable. It is hoped that release of the new instrument (VCOPS) at this time
      will allow others to join in determining the clinical and experimental validity
      of this scale.

PMID- 8300868
TI  - Sense of humor and dimensions of personality.
AB  - Previous researchers have demonstrated relationships between sense of humor and
      personality. Most have viewed sense of humor from the perspective of humor
      appreciation. Others have taken the approach that sense of humor has two factors:
      appreciation and creativity. Our approach has been to look at sense of humor as
      made up of creativity and several additional elements. The present study reports
      on the factor analysis of a Multidimensional Sense of Humor Scale, as well as
      correlates of various elements of sense of humor with personality traits assessed
      by the Edwards Personal Preference Schedule. Relationships by humor scale factors
      are reported, as are differences between those high and low in sense of humor
      within a sample of 426 individuals, 18 through 90 years of age.

PMID- 8300869
TI  - Use of MCMI subtle and obvious subscales to detect faking.
AB  - College students (N = 241) completed the MCMI under different instructional sets.
      An index of differential endorsement of subtle and obvious MCMI items was found
      to discriminate more strongly than the MCMI Validity Scale between subjects
      instructed to answer honestly and subjects instructed to fake good, fake bad, or
      portray specific forms of psychopathology. In addition, differential endorsement
      of subtle and obvious items on MCMI subscales tended to discriminate more
      strongly than the MCMI Validity Scale between subjects instructed to answer
      honestly and subjects instructed to portray the forms of psychopathology assessed
      by the subscales. The use of the subtle-obvious distinction to assess the
      validity of the MCMI is discussed.

PMID- 8300870
TI  - The coping resources inventory for stress: a measure of perceived
      resourcefulness.
AB  - This article reviews previous studies with the Coping Resources Inventory for
      Stress (CRIS) and reports the results of a recent convergent/divergent study on
      six CRIS scales. CRIS scales have high internal consistency and test-retest
      reliabilities and appear to be useful in predicting illness, emotional distress,
      personality type, drug dependency, occupational choice, and life satisfaction.
      The convergent/divergent sample consisted of 68 graduate student volunteers in a
      southeastern urban university. Each of the CRIS scales converged with its
      validating test and diverged from a test that measures a different construct.
      Results offer considerable support for the construct validity of CRIS scales and
      suggest that it may be a promising research and clinical instrument for the study
      of stress coping.

PMID- 8300871
TI  - Development of a structured interview scale for measuring quality of life of the
      severely mentally ill.
AB  - An objective, semi-structured interview questionnaire (QOLIS) was designed and
      tested with 201 severely mentally ill people who were living in a state hospital
      and in community residential facilities. Factor analysis resulted in eight
      factors with face validity and acceptable coefficient alphas. The factors were
      found to be related meaningfully to overall level of functioning, total symptom
      scores, self-reported life satisfaction, and an established objective measure of
      quality of life. Criterion validity was established and the QOLIS factors
      significantly differentiated people who were living in the community vs. living
      in a state hospital. These results suggest that the QOLIS has potential as a
      valid outcome measure and program evaluation tool.

PMID- 8300872
TI  - Construct validity of a self-report measure of alexithymia in a psychiatric
      inpatient sample.
AB  - This study examined the construct validity of a widely used self-report measure
      of alexithymia in a mixed-sex sample of 101 psychiatric inpatients (62 women and
      39 men). Contrary to expectations, scores on Shipko and Noviello's (1984)
      alexithymia scale (SNALEX) were: (1) correlated positively with a Rorschach index
      of verbal productivity; (2) unrelated to a Rorschach index of adaptive use of
      fantasy; (3) correlated negatively with scores on the MMPI L and K scales and
      correlated positively with scores on the MMPI F scale; and (4) correlated
      negatively with subject age. In addition, SNALEX scores were correlated
      negatively with scores on Klieger and Kinsman's (1980) alexithymia scale (KKALEX)
      in subjects of both sexes. These results do not support the construct validity of
      the SNALEX as a measure of alexithymia is psychiatric inpatients.

PMID- 8300873
TI  - Verbal vs. visual categories on the Wechsler Memory Scale-revised: how meaningful
      a distinction?
AB  - This study investigated whether the a priori classification of Wechsler Memory
      Scale-Revised (WMS-R) subtests into separate Verbal and Visual categories is
      warranted. Correlational and hierarchical clustering analyses found that (a)
      memory test performance correlated significantly with performance on subtests of
      Form II of the Luria-Nebraska Neuropsychological Battery (LNNB-II) that measure
      substrates of particular memory processes; and (b) subtests that appeared a
      priori to involve verbal skills clustered separately from those that appeared to
      involve nonverbal (visual) skills. However, the WMS-R Visual Paired Associates
      subtest did not cluster with the nonverbal scales as expected, and the LNNB-II
      Memory Scale appeared to be predominantly a test of verbal memory. Practical
      consequences of these findings were discussed.

PMID- 8300874
TI  - Delayed recall on the Wechsler Memory Scale-revised: the factor structure
      revisited.
AB  - Although delayed recall tasks are prominent features of the popular Wechsler
      Memory Scale-Revised (WMS-R), exploratory factor analyses consistently have
      failed to identify an associated delayed recall factor. The present study tested
      the hypothesis (Elwood, 1991b) that a delayed recall factor could be found by
      substituting percent retained (saving) scores for the existing WMS-R delayed
      recall subtest scores. Principal component analyses of age-corrected WMS-R
      immediate and save scores in a mixed clinical sample failed to find the
      hypothesized save factor. Both the scree and MAP tests retained one general
      memory factor, which accounted for 42.2% of the total variance. Independent
      statistical programs produced essentially equivalent results. Clinical
      implications of these findings are discussed.

PMID- 8300875
TI  - WAIS-R item difficulties with psychiatric inpatients.
AB  - Item difficulties for 10 WAIS-R subtests were determined for a sample of
      psychiatric inpatients (N = 150). Spearman correlation coefficients between
      psychiatric inpatient and standardization group rank orders were large and
      significant across all subtests except Object Assembly, which demonstrates the
      expected trend of increasing item difficulty for the psychiatric inpatient
      sample. Using linear regression, items with standardized residuals greater than
      two were judged to be significantly out of order for the psychiatric inpatient
      sample. Of the 165 WAIS-R items examined in this study, only 7 were found to be
      out of order. This result may have been due to chance and suggests that, in
      general, WAIS-R subtest item difficulty curves for psychiatric inpatients and the
      WAIS-R standardization group are comparable.

PMID- 8300876
TI  - Construct validity of a new computer-assisted cognitive neuromotor assessment
      battery in normal and inpatient psychiatric samples.
AB  - The construct validity of a computer-assisted battery of neuropsychological tests
      (CNT) was explored with psychiatric inpatients and normal volunteers. A principal
      components analysis of inpatient scores revealed simple reaction time, response
      accuracy, visuomotor skill, and complex processing and memory components. A
      similar factorial structure was found in normal subjects. However, complex
      processing and memory measures emerged as separate vigilance and memory
      components in volunteers. CNT tasks were correlated with nine subtests of the
      Neurobehavioral Cognitive Status Examination (NCSE). Simple reaction time, and
      complex processing and memory measures discriminated impaired from nonimpaired
      inpatients as defined by the NCSE. Recommendations for research on CNT, and
      computer-assisted tests in general, are made.

PMID- 8300877
TI  - Rey Auditory-Verbal Learning Test: structure analysis.
AB  - One of the major advantages of the Rey Auditory-Verbal Learning Test (AVLT) is
      its multiple measures of learning and memory. This study evaluated empirically
      whether the different scores are, in fact, not merely different expressions of a
      single factor, but, rather, measures of different memory domains. The Rey AVLT
      was administered to 146 normal subjects. Factor analyses produced one, two, or
      three factors depending on the combination of scores included in the analysis and
      on the criteria used to determine the number of factors. The basic factors
      identified were acquisition and retention. The latter can be subdivided further
      into storage and retrieval, thus yielding a total of three factors.

PMID- 8300878
TI  - The stability of WAIS-R IQ for 16-year-old students retested after 3 and 8
      months.
AB  - The stability of Wechsler Adult Intelligence Scale-Revised IQs was investigated
      for 52 students 16 years of age. Half of the subjects were retested after a 3
      month interval; half after an 18-month interval. Stability coefficients were
      uniformly high for both retest intervals. Gains in Verbal, Performance, and Full
      Scale IQ over 3 months were similar to practice effects reported for adult
      subjects. However, IQs for males retested after 18 months increased beyond the
      practice effect. Females retested after 18 months showed the same result only on
      Verbal IQ. The findings remind clinicians of the important distinction between
      relative and absolute stability, especially for 16-year-old students tested with
      the WAIS-R.

PMID- 8300879
TI  - Influence of patient caregivers on course of patient illness: "expressed emotion"
      and alternative measures.
AB  - The influence of the quality of care that patients receive during the course of
      their illness has been the subject of special scrutiny in the area of mental
      health. The concept of "expressed emotion" (EE) evolved in an effort to
      understand the impact of family and social environment on the vulnerability to
      relapse of schizophrenic patients. A semistructured interview, the Camberwell
      Family Interview, was developed to assess expressed emotion. This article
      examines the historical context, generalizability, methodological strengths and
      limitations of the construct of EE and the Camberwell Family Interview, as well
      as the nature and effects of treatment intervention programs designed to
      neutralize adverse effects of patient caretaker attitudes.

PMID- 8300880
TI  - Somatization and malingering for workers' compensation applicants: a cross
      cultural MMPI study.
AB  - A post hoc analysis was conducted of 60 Hispanics and 60 Caucasians who had filed
      claims under workers' compensation. The study examined cross-cultural differences
      of somatization and malingering as assessed by the MMPI. Somatization was
      assessed by analyzing two- and three-point code types based on scales 1 (Hs), 2
      (D), and 3 (Hy) of the MMPI, using the cut-off criterion of T > or = 70.
      Malingering was determined by analysis of the dissimulation index from the MMPI
      (F-K > +9). Significant differences were found for somatization; Hispanics were
      more likely to somatize. Minimal differences were found between Hispanic and
      Caucasian subjects on the malingering scale.

PMID- 8300881
TI  - The effect of domestic and economic stress on suicide rates in Canada and the
      United States.
AB  - The study of the variation in societal suicide rates still is guided primarily by
      Durkheim's (1897) theory. He proposed primarily a social integration/regulation
      theory of suicide. One useful way of exploring this theory is from a cross
      cultural perspective. Rates of birth, divorce, marriage, and unemployment were
      analyzed in comparison to rates of suicide from 1950 to 1985 in Canada and the
      United States. Results generally supported Durkheim's theory except for marriage.
      There was no association between marriage and suicide in Canada, whereas in the
      United States marriage had a protective effect once other variables were taken
      into account. Divorce rates were associated positively and birth rates associated
      negatively with suicide in both countries. Unemployment rates added little
      predictive power to suicide rates. A historical perspective and caution about
      overgeneralizing the results are presented.

PMID- 8300882
TI  - Cocktail strategy: complications and limitations.

PMID- 8300883
TI  - Outcomes research: exploring the unanticipated.

PMID- 8300884
TI  - Postmarketing surveillance: curriculum for the clinical pharmacologist. Part II:
      Clinical and regulatory considerations.
AB  - This is the second of a two-part series that develops a curriculum on
      postmarketing surveillance. With the ongoing emphasis on drug safety and possible
      earlier marketing of drugs, this becomes an essential element of clinical
      pharmacology training. The usual educational focus on drug safety is a
      pharmacokinetic or pharmacodynamic perspective on a specific drug or drug class,
      perhaps in the context of clinical trial study design and analysis. This
      curriculum complements this approach and provides an overview of drug safety
      surveillance from regulatory and epidemiologic perspectives.

PMID- 8300885
TI  - Angiotensin II receptor blockade: an innovative approach to cardiovascular
      pharmacotherapy.
AB  - Through the multiple actions of angiotensin II (AII), the renin-angiotensin
      system (RAS) participates in cardiovascular homeostasis. Angiotensin II acts by
      binding to specific membrane-bound receptors, which are coupled to one of several
      signal transduction pathways. These AII receptors exhibit heterogeneity,
      represented by AT1 and AT2 receptor subtypes. The AT1 receptor mediates the major
      cardiovascular action of the RAS. This receptor has been cloned from multiple
      species, disclosing features consistent with a transmembrane, G-protein-linked
      receptor. Further AII receptor heterogeneity is evident by the cloning of
      isotypes of the AT1 receptor. Blocking the interaction of AII with its receptor
      is the most direct site to inhibit the actions of the RAS. Many AII receptor
      antagonists, including peptide analogs of AII and antibodies directed against
      AII, possess unfavorable properties that have limited their clinical utility. The
      discovery and further development of imidazole compounds with AII antagonist
      properties and favorable characteristics, however, has promise for clinical
      utility. The leader in this field is a selective AT1 receptor antagonist losartan
      (previously known as DuP 753 or MK-954). Losartan was demonstrated to be an
      effective antagonist of many AII-induced actions and an effective
      antihypertensive agent in many animal models of hypertension (HTN). Losartan also
      demonstrated secondary benefits in preventing stroke, treating congestive heart
      failure (CHF), and delaying the progression of renal disease in animal models.
      Clinical studies confirm the AII antagonist action of losartan and suggest that
      losartan will be effective in the treatment of essential HTN. AII antagonism is
      likely to provide useful treatment in essential HTN and CHF, conditions in which
      the RAS is known to play a major role. The utility of AII antagonism may extend
      beyond that of HTN and CHF, as suggested by the potential usefulness of
      angiotensin-converting enzyme (ACE) inhibition in the treatment or prevention of
      many other diseases. The key advantage AII antagonists provide over ACE
      inhibitors is that they may avoid unwanted side effects, related to bradykinin
      potentiation with the latter drugs. The AII antagonists will help determine the
      role of the RAS in physiologic regulation and in the pathophysiology of various
      disease states.

PMID- 8300886
TI  - External imaging of atherosclerosis in rabbits using an 123I-labeled synthetic
      peptide fragment.
AB  - The oligopeptide fragment of apolipoprotein B, SP-4, has demonstrated pronounced
      uptake in the healing edges of balloon-injured rabbit aortic endothelium. To
      assess 123I-labeled SP-4 for identification of atherosclerotic plaques by gamma
      camera imaging, 14 Watanabe heritable hyperlipidemic (WHHL) and 5 normal rabbits
      were imaged 5 minutes and 12 and 24 hours after intravenous injection of 123I-SP
      4. In addition, two WHHL and two normal rabbits were injected with 125I-SP-4 for
      autoradiography. Twelve of the 14 WHHL, but none of the normal, rabbits had
      visually apparent focal radioiodine accumulation in the region of the aorta.
      Focus-to-lung and focus-to-heart count ratios were 2.4 +/- 1.3 and 1.0 +/- 0.4,
      respectively. Five of the visually positive WHHL rabbits were reimaged 4 and 8
      weeks later with 123I-NaI and 123I-SP-2 (an apo E peptide), respectively, as
      negative controls. Perceptible, but faint, aortic localization of 123I-NaI and of
      123I-SP-2 was seen in only one animal each. The distributions of atherosclerotic
      lesions on photographs of the opened WHHL aortas and of film blackening on 125I
      SP-4 autoradiograms were identical. In contrast, the two normal rabbit aortas did
      not exhibit plaques on photographs or film blackening on autoradiograms. Thus, in
      an animal model closely simulating human atherosclerotic disease, SP-4 localizes
      specifically in aortic atherosclerotic lesions.

PMID- 8300887
TI  - The relationship between the degradation of prostacyclin in blood and
      antiplatelet drug effects in patients with atherosclerosis.
AB  - Blood and plasma from 109 patients with atherosclerosis and 70 healthy volunteers
      were tested to study the rate of prostacyclin (PGI2) hydrolysis. It has been
      reported that patients with atherosclerosis have the enhanced velocity of PGI2
      degradation. The increase in the velocity was more marked in blood than in
      plasma. The significant negative correlation between antiaggregation effects of
      pentoxifylline, nifedipine, and dipyridamole and the velocity of PGI2 degradation
      in the patients was found. These data suggest that the increase of PGI2
      biosynthesis by the drugs studied can enhance their antiaggregation effect if
      processes of PGI2 degradation in blood are not accelerated.

PMID- 8300888
TI  - Ketoprofen pharmacokinetics in the elderly: influence of rheumatic disease, renal
      function, and dose.
AB  - An age-related accumulation of ketoprofen due to a reduced clearance has been
      reported in the elderly. Other studies have not observed these changes in the
      kinetics of unchanged ketoprofen, but have reported increased plasma levels and
      reduced urinary excretion of conjugated ketoprofen. The authors examined the
      effects of dose, renal function, and the presence of arthritis on the
      stereoselective kinetics of ketoprofen in five nonarthritic and six arthritic
      elderly subjects. There was a significant difference in renal function (CLCr,
      mL/min; arthritic, 71.8 +/- 12.3, nonarthritic, 91.4 +/- 11.1), but not in age or
      weight between the two groups. Subjects received 50 mg and then 150 mg enteric
      coated racemic ketoprofen, and plasma and urine samples were collected for 24
      hours. No significant differences in CL/F, area under the curve (AUC), half-life
      (t1/2), time to reach peak concentration (tmax), or maximum peak plasma
      concentration (Cmax) were found between groups or between doses, and values were
      similar to those previously reported in young adults. Urinary ketoprofen
      conjugate (S:R) ratio was 1.6 +/- .25 and 1.65 +/- .27 for arthritic and
      nonarthritic subjects. Greater amounts of conjugated ketoprofen enantiomers were
      present in the plasma of the arthritic compared with nonarthritic subjects. Renal
      clearance of ketoprofen conjugates exhibited stereoselectivity (R > S), and was
      decreased in the arthritic group. Significant changes in the kinetics of
      unchanged ketoprofen was not found to occur in elderly subjects in the presence
      or absence of rheumatic disease or moderate renal impairment.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8300889
TI  - Clinical cardiotoxicity of 5-fluorouracil.
AB  - 5-Fluorouracil is widely known to be toxic to the hematopoietic and
      gastrointestinal systems. It also has cardiac toxicity, but this is perceived to
      be rare. During a 16-month period from January 1990 through April 1991,
      approximately 910 patients were treated with 5-fluorouracil. Five of these
      developed life-threatening toxicity consistent with coronary artery spasm for an
      incidence of .55%. The acute events occurred on the third or fourth day of the 5
      day infusion and after the fourth intravenous bolus in the patient on bolus
      therapy. Each of the patients had ST elevation and ventricular arrhythmias, four
      had acute myocardial infarction, and two had cardiac arrests. In these cases and
      those previously reported, cardiac toxicity is consistent with drug- or
      metabolite-mediated increases in coronary vasomotor tone and spasm, leading to
      the full spectrum of signs and symptoms of myocardial ischemia in susceptible
      individuals.

PMID- 8300890
TI  - Use of lower body negative pressure to counter symptoms of orthostatic
      intolerance in patients, bed rest subjects, and astronauts.
AB  - This report briefly discusses some aspects of autonomic cardiovascular
      dysfunction as related to changes in orthostatic function in patients, bed rest
      subjects, and astronauts. This relationship is described in normal individuals to
      provide the basis for discussion of parameters that may be altered in patients,
      bed rest subjects, and astronauts. The relationships between disease states, age,
      periods of weightlessness during space flight, and autonomic dysfunction, and
      their contribution to changes in orthostatic tolerance are presented. The
      physiologic effects of lower body negative pressure are illustrated by presenting
      data obtained in bed rest subjects and in astronauts. Finally, the usefulness of
      lower body negative pressure to counter symptoms of orthostatic intolerance in
      patients, bed rest subjects, and astronauts is discussed.

PMID- 8300891
TI  - Comparison of the pharmacokinetics of E2020, a new compound for Alzheimer's
      disease, in healthy young and elderly subjects.
AB  - E2020, a central-acting cholinesterase inhibitor, is now under clinical
      development as a potential therapeutic agent for senile dementia of Alzheimer
      type. In the current study, the authors compared the pharmacokinetics of this
      drug after single oral administration in 12 healthy young volunteers (20-27 years
      of age) and 6 elderly volunteers (65-82 years of age). The subjects received a
      single 2-mg oral dose of E2020 after a meal. Blood samples for determination of
      the drug level were collected over 168 hours after drug administration and were
      measured by specific high-pressure liquid chromatography methods with ultraviolet
      detection. E2020 was generally well tolerated by all subjects of both groups. The
      plasma elimination half-life of the beta-phase (t 1/2 beta) and time to maximum
      peak plasma concentration (tmax) were significantly longer in the elderly than in
      the young: t 1/2 beta, 103.8 +/- 40.6 versus 59.7 +/- 16.1 hours; and tmax, 5.2
      +/- 2.8 versus 3.4 +/- 1.5 hours, respectively. There were no statistically
      significant differences in maximum peak plasma concentration and area under the
      curve between the two groups. The mean (+/- standard deviation) oral clearance
      (Cl/F) in the elderly (9.1 +/- 2.4 L/h) was similar to that in the young (10.6 +/
      2.7 L/h). The volume of distribution in the steady state (Vdss/F) was
      significantly larger in the elderly than that in the young: 1217.2 +/- 223.2
      versus 852.5 +/- 147.7 L, respectively. These results suggested that the drug was
      absorbed more slowly and distributed more widely and thoroughly, but that its
      clearance from the body is essentially unaffected by age.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8300892
TI  - Facilitation of adaptation and acute tolerance to stressful sensory input by
      doxepin and scopolamine plus amphetamine.
AB  - This work characterizes a new methodologic and pharmacologic approach to control
      terrestrial and space motion sickness (SMS). The experimental design allowed
      separate evaluation of drug action on susceptibility and adaptability, and used
      repeated measures to approximate the chronic stressful motion of microgravity.
      Daily exposure to cross-coupled angular acceleration for 5 consecutive days
      demonstrated that the efficacy of doxepin and scopolamine plus amphetamine in the
      prevention of autonomic system dysfunction was not only apparent on the first
      test day (P < .01), but was also evident in the substantially enhanced resistance
      developed over the 5-day test period (P < .01) as compared with placebo. This
      indicates that daily use of these medications does not diminish therapeutic
      efficacy (tolerance). The efficacy of doxepin was anticipated because it
      possesses pharmacologic properties similar to those of established anti-motion
      sickness drugs. Comparable efficacy after doxepin loading for 4 hours, 3 days, or
      21 days suggests a mechanism distinct from its antidepressant effects, possibly
      related to its potent antihistaminergic actions. Use of doxepin has operational
      significance to the National Aeronautics and Space Administration, in comparison
      with current preparations of scopolamine plus amphetamine, because of doxepin's
      minimal impact on cognitive performance, and most importantly, its favorable
      pharmacokinetic profile, particularly its long half-life.

PMID- 8300893
TI  - A study of pharmacokinetic interaction between buspirone and alprazolam at steady
      state.
AB  - The steady-state pharmacokinetic interaction between buspirone and alprazolam was
      evaluated in a parallel study with two groups of 12 male volunteers each. On days
      1 to 7, group I subjects received a 1-mg alprazolam tablet every 8 hours (q8h)
      (TRT 1) and group II subjects received 2 x 5-mg buspirone tablets q8h (TRT 2). On
      days 8 through 14, all subjects received a combination of 1-mg alprazolam and 2 x
      5-mg buspirone tablets q8h (TRT 3). Plasma samples, collected 0 to 8 hours after
      the morning dose on days 7 and 14, were analyzed for buspirone, alprazolam and
      their metabolites, 1-PP, and alpha-HO-alprazolam, respectively. Additional
      samples were collected before the morning dose on days 5 and 6 of each session to
      monitor the attainment of steady state. Steady-state pharmacokinetic parameters
      Cmax, Tmax, AUC0-8, and Cmin were calculated. The results indicated that for
      alprazolam, there was a small (< 10%) increase in Cmax and AUC when
      coadministered with buspirone. For buspirone, there was a 10% and 29% increase in
      Cmax and AUC, when coadministered with alprazolam. These values were within the
      normal variability observed with this class of drugs. Except for a 14% decrease
      in Cmin for alpha-HO-alprazolam, coadministration of buspirone and alprazolam did
      not affect the parameters for the metabolites. The results of this study suggest
      that coadministration of buspirone and alprazolam did not markedly affect the
      steady-state pharmacokinetics of either drug.

PMID- 8300894
TI  - Selective alpha-1 adrenoceptor blockade and renal sodium handling in humans.
AB  - In animal studies, acute interruption of the activity of renal alpha-1
      adrenoceptors by renal denervation results in an increase in sodium and water
      excretion. Chronic selective blockade of alpha-1 adrenoceptors by prazosin in
      clinical practice has been associated with sodium retention, however. Previous
      studies in the authors' laboratory using chronic alpha-1 blockade in the rat have
      demonstrated a decreased ability to excrete a saline load. Therefore, the authors
      determined the effect of chronic selective alpha-1 adrenoceptor blockade with
      prazosin in eight healthy volunteers. Volunteers underwent a water load to
      establish a water diuresis, followed by a modest saline load using intravenous
      saline (0.9% NaCl). This experimental protocol was repeated after four weeks of
      prazosin therapy (5 mg twice daily). Prazosin failed to alter body weight (73.6
      +/- 4.2 versus 74.5 +/- 4.1 kg, expressed as mean +/- standard error), mean blood
      pressure (86.7 +/- 2.7 versus 84.7 +/- 2.3 mm Hg), creatinine clearance (127.0 +/
      8.5 versus 133.4 +/- 12.0 mL/min), renal blood flow as measured by para
      aminohippurate clearance (1202 +/- 88 versus 1175 +/- 69 mL/min) and the 24-hour
      sodium excretion (115 +/- 11 versus 128 +/- 19 mmol). In the presence of the
      experimentally induced saline load, chronic prazosin treatment was associated
      with a decreased free water clearance (e.g., hour 3, 7.8 +/- .7 versus 6.3 +/-
      2.0 mL/min; P < or = .05) and fractional excretion of sodium (e.g., hour 3, 1.48
      +/- .10 versus 1.15 +/- .13; P < or = .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300895
TI  - Bioequivalence of a 17 beta-estradiol hydroxypropyl-beta-cyclodextrin complex in
      postmenopausal women.
AB  - Five postmenopausal women received single doses of a 0.675 mg estradiol
      hydroxypropyl-beta-cyclodextrin (estradiol-HP beta CD) sublingual tablet by the
      sublingual and oral route. A single dose of a 1 mg micronized estradiol tablet
      was given orally for comparison. Blood samples were obtained over 48 hours for
      measurement of estradiol, estrone, luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) concentrations. Sublingual administration produced
      faster and significantly higher peak estradiol concentrations than after oral
      administration of either estradiol-HP beta CD or micronized estradiol. The
      concentration-time area under the curve of estradiol after sublingual estradiol
      HP beta CD was also significantly larger than after oral administration of either
      estradiol-HP beta CD or micronized estradiol, reflecting a larger estradiol
      bioavailability. The estradiol/estrone concentration ratio after sublingual
      estradiol-HP beta CD revealed a predominance of estradiol for the first 2 hours
      after the dose, followed by an estrone predominance. Both oral doses produced a
      predominant delivery of estrone to the systemic circulation. There was not
      difference in time-averaged LH suppression between the three phases. However,
      estradiol-HP beta CD sublingually produced greater FSH suppression than oral
      micronized estradiol.

PMID- 8300896
TI  - Aldose reductase inhibitory and uricosuric activities of FK366 in healthy
      volunteers.
AB  - The pharmacokinetics, and aldose reductase (AR) inhibitory and uricosuric
      activities of FK366 were studied in healthy volunteers given a single oral dose
      of 150, 300, or 600 mg after fasting, 600 mg after a meal, or 300 mg twice a day
      for 8 days after meals. The AR inhibition was assessed by the percent reduction
      from the predrug dulcitol values in red blood cells converted from exogenous
      galactose by AR. Aldose reductase inhibition paralleled the plasma concentrations
      of FK366, with maximum inhibitions of 31.6, 48.0, and 56.9% at doses of 150, 300,
      and 600 mg, respectively. With multiple dosing, the inhibition scarcely differed
      between the first (41.8%) and last doses (41.5%). Serum uric acid decreased dose
      dependently, with a minimum concentration of 4.0 mg/dL (predrug: 5.5 mg/dL) 8
      hours after receiving 600 mg. With multiple dosing, serum uric acid levels
      declined rapidly and remained at a concentration of 3.1 mg/dL beginning at day 3.
      Urinary excretion of uric acid was high on day 1 (879 mg/day), but decreased
      significantly to 654 mg/day on day 2 and then stabilized. The pharmacokinetics of
      FK366 were linear over the dose range studied, with an elimination half-life of
      8.2 hours and urinary recovery of 27.2% as unchanged drug. FK366 was well
      tolerated by all subjects.

PMID- 8300897
TI  - Morphology of astrocytes and oligodendrocytes during development in the intact
      rat optic nerve.
AB  - The detailed three-dimensional morphology of macroglial cells was determined
      throughout postnatal development in the intact rat optic nerve, a central nervous
      system white matter tract. Over 750 cells were analyzed by intracellular
      injection of horseradish peroxidase or Lucifer Yellow to provide a new
      perspective of glial differentiation in situ. Retrograde analysis of changes in
      glial morphology allowed us to identify developmental timetables for three
      morphological subclasses of astrocytes and oligodendrocytes, and to estimate
      their time of emergence from undifferentiated glial progenitors. Glial
      progenitors were recognised throughout postnatal development and persisted in 35
      day-old nerves, where we suggest they represent adult progenitor cells.
      Astrocytes were present at birth, but the majority of these cells developed over
      the first week as three morphological classes emerged having either transverse,
      random, or longitudinal process orientation. Several lines of evidence led us to
      believe that the majority of astrocytes in the rat optic nerve were morphological
      variations of a single cell type. Young oligodendrocytes were first observed 2
      days after birth, indicating that they diverged from progenitors at or near this
      time. During early development these cells extended a large number of fine
      processes, which then bifurcated and extended along axons. Later, as myelination
      proceeded, oligodendrocytes exhibited fewer processes which grew symmetrically
      and uniformly along the axons, resulting in a highly stereotypic mature
      oligodendrocyte form. Our analysis of oligodendrocyte growth suggests that these
      cells did not myelinate axons in a random manner and that axons may influence the
      myelinating processes of nearby oligodendrocytes.

PMID- 8300898
TI  - Effect of unilateral partial cochlear lesions in adult cats on the representation
      of lesioned and unlesioned cochleas in primary auditory cortex.
AB  - We examined the effect of unilateral restricted cochlear lesions in adult cats on
      the topographic representations ("maps") of the lesioned and unlesioned cochleas
      in the primary auditory cortex (AI) contralateral to the lesioned cochlea.
      Frequency (tonotopic) maps were derived by conventional multineuron mapping
      procedures in anesthetized animals. In confirmation of a study in adult guinea
      pigs (Robertson and Irvine [1989] J. Comp. Neurol. 282:456-471), we found that 2
      11 months after the unilateral cochlear lesion the map of the lesioned cochlea in
      the contralateral AI was altered so that the AI region in which frequencies with
      lesion-induced elevations in cochlear neural sensitivity would have been
      represented was occupied by an enlarged representation of lesion-edge frequencies
      (i.e., frequencies adjacent to those with elevated cochlear neural sensitivity).
      Along the tonotopic axis of AI the total representation of lesion-edge
      frequencies could extend up to approximately 2.6 mm rostal to the area of normal
      representation of these frequencies. There was no topographic order within this
      enlarged representation. Examination of threshold sensitivity at the
      characteristic frequency (CF, frequency to which the neurons were most sensitive)
      in the reorganized regions of the map of the lesioned cochlea established that
      the changes in the map reflected a plastic reorganization rather than simply
      reflecting the residue of prelesion input. In contrast to the change in the map
      of the lesioned contralateral cochlea, the map of the unlesioned ipsilateral
      cochlea did not differ from those in normal animals. Thus, in contrast to the
      normal very good congruency between ipsilateral and contralateral AI maps, in the
      lesioned animals ipsilateral and contralateral maps differed in the region of AI
      in which there had been a reorganization of the map of the lesioned cochlea.
      Outside the region of contralateral map reorganization, ipsilateral and
      contralateral AI maps remained congruent within normal limits. The difference
      between the two maps in the region of contralateral map reorganization suggested,
      in light of the physiology of binaural interactions in the auditory pathway, that
      the cortical reorganization reflected subcortical changes. Finally, response
      properties of neuronal clusters within the reorganized map of the lesioned
      cochlea were compared to normative data with respect to threshold sensitivity at
      CF, the size of frequency "response areas," and response latencies. In the
      majority of cases, CF thresholds were similar to normative data. The frequency
      "response areas" were slightly less sharply tuned than normal, but not
      significantly. Response latencies were significantly shorter than normal in three
      animals and significantly longer in one animal.

PMID- 8300899
TI  - Ramification pattern and ultrastructural characteristics of the serotonin
      immunoreactive neuron in the antennal lobe of the moth Manduca sexta: a laser
      scanning confocal and electron microscopic study.
AB  - The two antennal lobes, the primary olfactory centers of the brain, of the moth
      Manduca sexta each contain one neuron that displays serotonin immunoreactivity.
      The neuron projects out of the antennal lobe and sends branches into ipsi- and
      contralateral protocerebral areas. An axon-like process extends from the
      contralateral protocerebrum to, and terminates in, the contralateral antennal
      lobe. In order to begin to investigate the possible role of this unique neuron in
      olfactory information processing, we have used laser scanning confocal
      microscopic and electron microscopic immunocytochemical techniques to study the
      ramification pattern, ultrastructural characteristics, and synaptic connections
      of the neuron in the antennal lobes of female adult Manduca sexta. The neuron
      ramifies extensively in the antennal lobe contralateral to the cell body. The
      ramifications, mainly in the base and center of each glomerulus, do not overlap
      with those of the sensory axons from the antenna. This finding suggests that the
      serotonin-immunoreactive neuron may not receive direct input from sensory
      neurons, and that it may modulate the activity of the neurons of the antennal
      lobe rather than that of the sensory neurons. In the electron microscope, the
      neuron exhibits large dense-cored vesicles and small, clear round vesicles. In
      the antennal lobe ipsilateral to the cell body, the primary neurite of the
      serotonin-immunoreactive neuron is unbranched and lacks detectable synaptic
      connections. The ramifications in the contralateral antennal lobe, however,
      participate in synaptic connections. At very low frequency, contralateral
      branches form synapses onto unlabeled processes and also receive synapses from
      unidentified neurons in the glomeruli, indicating that the neuron may participate
      directly in synaptic processing of olfactory information. The high ratio of
      output to input synapses made by the serotonin-immunoreactive processes in the
      contralateral antennal lobe is consistent with the idea that this neuron may
      receive synaptic input via its bilateral branches in the protocerebrum and then
      send information to the contralateral antennal lobe where the neuron may exert
      feedback or modulatory influences on olfactory information processing in the
      glomeruli.

PMID- 8300900
TI  - Neurotoxic effects of neonatal injections of monosodium L-glutamate (L-MSG) on
      the retinal ganglion cell layer of the golden hamster: anatomical and functional
      consequences on the circadian system.
AB  - In rodents, daily injection of neurotoxic monosodium L-glutamate (MSG) during the
      postnatal period induces retinal lesions, optic nerve degeneration with an
      alteration of visual pathway and an absence of the b-wave in the
      electroretinogram. Despite this damage, electrophysiological responses subsist in
      the lateral geniculate bodies and synchronization of circadian rhythms to the
      light/dark cycle can still occur. Using two formal properties of the circadian
      system (entrainment and phase-shift by light), we assessed the functionality of
      retinal projections to the circadian clock in MSG-treated hamsters. Displaced
      amacrine and ganglion cell populations were quantified and retinal terminals in
      the suprachiasmatic nuclei were estimated. Animals received daily doses of
      glutamate during the first ten days after birth according to two protocols. The
      two treatments similarly destroyed 56% of the overall population of the ganglion
      cell layer: 30% of displaced amacrine and 89% of ganglion cells. Surviving
      ganglion neurons (7,500 cells) were evenly distributed across the entire retina
      except in one area of high cell density located in the temporoventral quadrant.
      Retinal projections of the "image-forming" pathway were drastically reduced in
      the dorsal lateral geniculate bodies, less in their ventral part. The "nonimage
      forming" pathway was also affected since the volume of labeled terminals in the
      suprachiasmatic nuclei was reduced by one-half to one-third. Nevertheless,
      treated hamsters exhibited a free-running locomotor activity rhythm after several
      months in constant darkness, could be entrained by the light/dark cycle and phase
      shifted by light pulses. These results suggest that a damaged retinohypothalamic
      tract can still assume the photic entrainment of the circadian clock.

PMID- 8300901
TI  - Heterogeneous distribution of glycinergic and GABAergic afferents on an
      identified central neuron.
AB  - Immunocytochemical methods were used on serial sections to study the glycine- and
      gamma-amino butyric acid (GABA)ergic innervations of the teleost Mauthner (M)
      cell. We found different distributions for the boutons containing the two amino
      acids. Endings filled with GABA predominate on the distal portion of the lateral
      dendrite (LD) while glycine-positive profiles are more abundant on the soma and
      within the axon cap (AC), a specialized neuropil surrounding the M-cell initial
      segment. A few endings containing both transmitters are present on the soma and
      on the small dendrites issuing ventrally from it. At this level some glutamic
      acid decarboxylase (GAD)-containing boutons face glycine receptor-93 kD
      associated protein, an observation suggesting that the associated glycine
      functions as a neurotransmitter. Elsewhere on the M-cell, where glycine and GABA
      are not colocalized, GAD-positive profiles were never observed in front of
      postsynaptic differentiations with 93 kD labelling. GABA was detected in the
      small vesicle boutons (SVBs), most of them, following the classification of
      Tuttle et al., J. Comp. Neurol. 265:254-274, 1987, belonging to the A-type, while
      glycine was found in the unmyelinated club endings in the AC, and in C- and B
      type SVBs, outside this region. All terminals established symmetrical synapses
      and were filled with a population of pleiomorphic vesicles. Boutons with GABA
      also contained numerous dense-core vesicles suggesting the presence of an
      associated peptide(s). A quantitative study of the transmitter content based on
      the number of the gold particles revealed a variable intensity of the labelling
      over certain profiles. For GABA, it was maximum at the tip of the LD and it
      decreased proximally. In contrast, the staining density was constant for glycine
      along all parts of the cell, except for the ventral dendrite (VD) where it
      decreased progressively. Taken together, these data suggest that the amino acid
      content varies, depending upon the location of the synapses on their target
      neuron.

PMID- 8300902
TI  - Ferritin, transferrin, and iron in selected regions of the adult and aged rat
      brain.
AB  - Iron is necessary for normal neural function but it must be stringently regulated
      to avoid iron-induced oxidative injury. The regulation of systemic iron is
      through the proteins transferrin (iron mobilization) and ferritin (iron
      sequestration). This study examines the cellular and regional distribution of
      iron and the iron-related proteins ferritin and transferrin in selected regions
      of the adult and aged rat brain. This information is a necessary prerequisite to
      understanding the mechanism by which iron homeostasis is maintained in the brain.
      The predominant cell type containing ferritin, transferrin, and iron throughout
      the brain at all ages is the oligodendrocyte. Neurons in most brain regions
      contain granular iron deposits which become more apparent with age. Ferritin and
      iron are also present in microglial cells in all brain regions, but are
      particularly abundant in the hippocampus. These latter cells visibly increase in
      number in all brain regions as the animal approaches senescence. Another area in
      which immunostaining is notable is surrounding the III ventricle, where
      transferrin is found in the choroid plexus and ependyma and ferritin and iron are
      present in tanycytes. The results of this study indicate an important role for
      neuroglia in the regulation of iron in the brain and also implies that a
      transport system may exist for the transfer of iron between the brain and
      cerebrospinal fluid. In the normal rodent brain, the principal cell of iron
      regulation is the oligodendrocyte; however, the role of microglial cells in the
      sequestration and detoxification of iron may be significant, particularly as the
      animal ages. With age there is an increase in stainable iron in neurons without a
      concomitant increase in neuronal ferritin immunostaining, suggesting a ferritin
      independent accumulation of neuronal iron with age.

PMID- 8300903
TI  - The candelabrum cell: a new interneuron in the cerebellar cortex.
AB  - A new cell type is described in silver-impregnated sections of the rat cerebellar
      cortex, uniformly distributed through all the cerebellar folia. The soma is
      rather small, roughly pyriform, vertically oriented, and squeezed, in a sandwich
      like manner, between the Purkinje cell somata. One or two thick dendrites arise
      from the upper pole of the cell body and course through the entire molecular
      layer, dividing into a few, slightly oblique, branches that can reach the pia
      mater. These dendrites are covered with irregularly distributed spines. Some more
      slender dendrites emerge from the lower part of the cell body, or from the
      proximal trunk of a molecular dendrite, and spread tortuously for a short
      distance in the upper granular layer. A thick initial segment emerges directly
      from the soma or from the proximal portion of a dendrite, the axon winding then
      horizontally through or just above the Purkinje cell layer. During this
      horizontal course it gives off vertically oriented beaded branches ascending
      through the major part of the molecular layer. These branches, rather closely
      spaced, occupy different parasagittal planes, separated by about 10 to 30
      microns. This axonal arborisation can thus be compared with a candelabrum. The
      peculiar three-dimensional spread of the axonal collaterals suggests a functional
      relationship between these branches and the dendritic trunks of neighbouring
      Purkinje cells. A comparative analysis of the morphological differences between
      this candelabrum interneuron and the other corticocerebellar interneurons found
      in the vicinity of the ganglionic layer confirms the specificity of this new cell
      class.

PMID- 8300904
TI  - The unipolar brush cell: a neglected neuron of the mammalian cerebellar cortex.
AB  - We describe with a variant of the Golgi method a new type of neuron that is
      prominently represented in the granular layer of the mammalian
      vestibulocerebellum but is presently neglected in all major accounts on the
      cerebellum. These neurons, here termed unipolar brush cells, are intermediate in
      size between granule cells and Golgi cells. They typically have a thin and
      presumably myelinated axon, and a single and stubby dendrite whose tip forms a
      tightly packed group of branchlets resembling a paintbrush. The branchlets often
      intertwine with the digitiform claws of granule cell dendrites and are
      occasionally approached by Golgi cell dendrites, indicating that the unipolar
      brush cells may share the input of the other granular layer neurons. Branchlets
      of neighboring unipolar brush cells converging into the same neuropil island also
      occur. The brush-like tip of the unipolar cell engulfs one or two mossy fiber
      rosettes to form an extensive synapse that appears to close recurrent loops
      involving the vestibular nuclei. Positive feedback in these loops could help to
      explain several motor responses and drive mechanisms of extended duration that
      are controlled by the ventral cerebellum.

PMID- 8300905
TI  - The hippocampal CA3 network: an in vivo intracellular labeling study.
AB  - The intrahippocampal distribution of axon collaterals of individual CA3 pyramidal
      cells was investigated in the rat. Pyramidal cells in the CA3 region of the
      hippocampus were physiologically characterized and filled with biocytin in
      anesthetized animals. Their axonal trees were reconstructed with the aid of a
      drawing tube. Single CA3 pyramidal cells arborized most extensively in the CA1
      region, covering approximately two-thirds of the longitudinal axis of the
      hippocampus. The total length of axon collaterals in the CA3 region was less than
      in CA1 and the axon branches tended to cluster in narrow bands (200-800 microns),
      usually several hundred microns anterior or posterior to the cell body. The
      majority of the recurrent collaterals of a given neuron remained in the same
      subfield (CA3a, b, or c) as the parent cell. CA3a neurons innervated
      predominantly the basal dendrites, whereas neurons located proximal to the hilus
      (CA3c) terminated predominantly on the apical dendrites of both CA1 and CA3
      cells. Two cells, with horizontal dendrites and numerous thorny excrescences at
      the CA3c-hilus transitional zone, were also labeled and projected to both CA3 and
      CA1 regions. All CA3 neurons projected some collaterals to the hilar region.
      Proximal (CA3c) neurons had numerous collaterals in the hilus proper. One CA3c
      pyramidal cell in the dorsal hippocampus sent an axon collaterals to the inner
      third of the molecular layer. CA3c pyramidal cells in the ventral hippocampus had
      extensive projections to the inner third of the dentate molecular layer, as well
      as numerous collaterals in the hilus, CA3, and CA1 areas, and several axon
      collaterals penetrated the subiculum. The total projected axon length of a single
      neuron ranged from 150 to 300 mm. On the basis of the projected axon length and
      bouton density (mean interbouton distance: 4.7 microns), we estimate that a
      single CA3 pyramidal cell can make synapses with 30,000-60,000 neurons in the
      ipsilateral hippocampus. The concentrated distribution of the axon collaterals
      ("patches") indicates that subpopulations of neurons may receive
      disproportionately denser innervation, whereas innervation in the rest of the
      target zones is rather sparse. These observations offer new insights into the
      physiological organization of the CA3 pyramidal cell network.

PMID- 8300906
TI  - The distribution of GABA-containing perikarya, fibers, and terminals in the
      forebrain and midbrain of pigeons, with particular reference to the basal ganglia
      and its projection targets.
AB  - Immunohistochemical techniques were used to study the distributions of glutamic
      acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) in pigeon forebrain
      and midbrain to determine the organization of GABAergic systems in these brain
      areas in birds. In the basal ganglia, numerous medium-sized neurons throughout
      the striatum were labeled for GABA, while pallidal neurons, as well as a small
      population of large, aspiny striatal neurons, labeled for GAD and GABA. GAD+ and
      GABA+ fibers and terminals were abundant throughout the basal ganglia, and
      GABAergic fibers were found in all extratelencephalic targets of the basal
      ganglia. Most of these targets also contained numerous GABAergic neurons. In
      pallial regions, approximately 10-12% of the neurons were GABAergic. The outer
      rind of the pallium was more intensely labeled for GABAergic fibers than the
      core. The olfactory tubercle region, the ventral pallidum, and the hypothalamus
      were extremely densely labeled for GABAergic fibers, while GABAergic neurons were
      unevenly distributed in the hypothalamus. GABAergic neurons and fibers were
      abundant in the dorsalmost part of thalamus and the dorsal geniculate region,
      while GABAergic neurons and fibers were sparse (or lightly labeled) in the
      thalamic nuclei rotundus, triangularis, and ovoidalis. Further, GABAergic neurons
      were abundant in the superficial tectal layers, the magnocellular isthmic
      nucleus, the inferior colliculus, the intercollicular region, the central gray,
      and the reticular formation. GABAergic fibers were particularly abundant in the
      superficial tectal layers, the parvocellular isthmic nucleus, the inferior
      colliculus, the intercollicular region, the central gray, and the interpeduncular
      nucleus. These results suggest that GABA plays a role as a neurotransmitter in
      nearly all fore- and midbrain regions of birds, and in many instances the
      observed distributions of GABAergic neurons and fibers closely resemble the
      patterns seen in mammals, as well as in other vertebrates.

PMID- 8300907
TI  - Projections of GABAergic and cholinergic basal forebrain and GABAergic preoptic
      anterior hypothalamic neurons to the posterior lateral hypothalamus of the rat.
AB  - Within the basal forebrain, gamma-aminobutyric acid (GABA)-synthesizing neurons
      are codistributed with acetylcholine-synthesizing neurons (Gritti et al. [1993]
      J. Comp. Neurol. 329:438-457), which constitute one of the major forebrain
      sources of subcortical afferents to the cerebral cortex. In the present study,
      descending projections of the GABAergic and cholinergic neurons were investigated
      to the lateral posterior hypothalamus (LHp) through which the medial forebrain
      bundle passes and where another major forebrain source of subcortical afferents
      is situated. Retrograde transport of cholera toxin b subunit (CT) from the LHp
      was combined with immunohistochemical staining for glutamic acid decarboxylase
      (GAD) and choline acetyl transferase (ChAT) using a sequential peroxidase
      antiperoxidase (PAP) technique. A relatively large number of GAD+ neurons
      (estimated at approximately 6,200), which represented > 15% of the total
      population of GAD+ cells in the basal forebrain (estimated at approximately
      39,000), were retrogradely labeled from the LHp. These cells were distributed
      through the basal forebrain cell groups, where ChAT+ cells are also located,
      including the medial septum and diagonal band nuclei, the magnocellular preoptic
      nucleus, and the substantia innominata, with few cells in the globus pallidus. In
      these same nuclei, a small number of ChAT+ cells were retrogradely labeled
      (estimated at approximately 800), which represented only a small percentage (<
      5%) of the ChAT+ cell population in the basal forebrain (estimated at
      approximately 18,000). Both the GAD+ and ChAT+ LHp-projecting neurons represented
      a small subset of their respective populations in the basal forebrain, distinct
      from the magnocellular, presumed cortically projecting, basal neurons. In
      addition to the GAD+ cells in the basal forebrain, GAD+ cells in the adjacent
      preoptic and anterior hypothalamic regions were also retrogradely labeled in
      significant numbers (estimated at approximately 5,500) and proportion (> 20%) of
      the total population (estimated at approximately 30,000) from the LHp. The
      retrogradely labeled GAD+ neurons were distributed in continuity with those in
      the basal forebrain through the lateral preoptic area, medial preoptic area, bed
      nucleus of the stria terminals, and anterior and dorsal hypothalamic areas. Of
      the large number of cells that project to the LHp in the basal forebrain and
      preoptic-anterior hypothalamic regions (estimated at approximately 66,000), the
      GAD+ neurons represented a significant proportion (> 15%) and the ChAT+ neurons a
      very small proportion (approximately 2%). The relative magnitude of the GABAergic
      projection suggests that it may represent an important inhibitory influence of
      the descending efferent output from the basal forebrain and preoptic-anterior
      hypothalamic regions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8300909
TI  - Development of the dendritic fields of layer 3 pyramidal cells in the kitten's
      visual cortex.
AB  - The cat's visual cortex is immature at birth and undergoes extensive postnatal
      development. For example, cells of layers 2 and 3 do not complete migration until
      about 3 weeks after birth. Despite the importance of dendritic growth for
      synaptic and functional development, there have been few studies of dendritic
      development in the cat's visual cortex to correlate with numerous studies of
      functional and synaptic development. Accordingly, we used the Golgi method to
      study the development of the dendrites of layer 3 pyramidal cells in the visual
      cortex of a series of cats ranging in age from 2 days to 3 years. Blocks of
      visual cortex were impregnated by the Golgi-Kopsch method and sectioned in the
      tangential plane. Layer 3 pyramidal cells were drawn with a camera lucida and
      analyzed by Sholl diagrams and vector addition. In kittens < 1 week old, these
      cells were very immature, with only an apical dendrite and no basal dendrites.
      Basal dendrites appeared during the second week. By 2 weeks, all of the basal
      dendrites had emerged from the soma, but they had few branches and were tipped
      with growth cones. By 4 weeks, they had finished branching but continued to grow
      in length until, by 5 weeks, they reached their adult size. Examination of the
      basal dendritic fields in the tangential plane revealed that their dendritic
      fields were more elongated at 2 weeks than at later ages, perhaps because of
      their smaller size. The distribution of dendritic field orientations was uniform
      at all ages except 3 and 4 weeks, when there was a preponderance of fields
      oriented in the rostrocaudal direction. Because dendritic growth and branching
      occurred very rapidly over a period that precedes and overlaps with the peak
      periods of synaptogenesis and of sensitivity to the effects of early visual
      experience, they may depend on afferent visual activity. The early emergence of
      primary dendrites, however, suggests that this process is independent of afferent
      activity. The coincident timing of dendritic branching with the presence of
      dendritic growth cones suggests that branching may occur at growth cones.

PMID- 8300908
TI  - Distribution and morphology of immunoreactive gonadotropin-releasing hormone
      (GnRH) neurons in the basal forebrain of ponies.
AB  - Recent reports have indicated that analysis of changes in the staining
      characteristics of gonadotropin-releasing hormone (GnRH) neurons and
      characterization of morphological plasticity of the related structural framework
      may help to elucidate the physiological mechanisms involved in neuroendocrine
      control of mammalian reproduction. Whether comparative studies will facilitate
      this process or simply elucidate species-specific mechanisms is not yet clear.
      The present study was performed in order to begin analysis of GnRH neurons in a
      seasonally breeding species that exhibits an unusually long ovulatory luteinizing
      hormone (LH) surge. To this end, light microscopy and image analysis were used to
      characterize distribution and morphology of GnRH neurons in 15 adult male and
      female ponies. Samples were collected in the middle of the normal ovulatory
      season. Unipolar, bipolar, and multipolar GnRH neurons were organized in a
      loosely defined continuum that extended from the medial septum to
      tuberoinfundibular areas in the medical basal hypothalamus (MBH). Most cells were
      bipolar, and the majority of neurons were located in the MBH. Fiber projections
      to the median eminence included presumptive pathways similar to those previously
      described in other species. Image analysis of cell size indicated that cells in
      the MBH were larger than those in preoptic areas and GnRH neurons in both of
      these locations were larger than neurons in rostral areas of the medial septum.
      Results from this experiment suggest that the large population of MBH GnRH
      neurons in the equine species is likely to be of primary importance to
      reproductive function, whereas cells in other areas are fewer and smaller.
      Further work is needed to characterize morphological characteristics that may be
      related to physiological fluctuations in reproductive function of the equine
      species.

PMID- 8300910
TI  - Immunoglobulin-producing tumours in dogs and cats.
AB  - Tumours with a plasmacytoid pattern taken from 32 dogs and four cats were
      examined for the presence of immunoglobulins, which would allow them to be
      designated as B-cell lymphomas. Within a total of 19 immunoglobulin-positive
      tumours, three types could be distinguished: extramedullary plasmacytoma (15),
      multiple myeloma (two) and immunocytoma (two). These tumours occurred in 18 of
      the dogs, and in one cat (extramedullary plasmacytoma). The characteristics of
      the immunoglobulin-producing tumours were investigated by light and electron
      microscopy as well as by immunohistochemical methods. Seventeen of the 19 tumours
      expressed lambda-type light chains and one tumour kappa-type light chains. Heavy
      chains were also synthesized by five tumours.

PMID- 8300911
TI  - Nude rats as a model of natural Pneumocystis carinii pneumonia: sequential
      morphological study of lung lesions.
AB  - A spontaneous infection with Pneumocystis carinii (P.c.) caused enzootic fatal
      pneumonia in a long-term experiment with athymic Rowett Nude (Han:RNU rnu/rnu)
      and New Zealand Nude (Han:NZNU rnuN/rnuN) rats. In order to reproduce the
      infection and to characterize the early pathogenesis of lung lesions, 13 young
      athymic Han:RNU and Han:NZNU rats from P.c.-free breeding colonies were housed
      together in one room with chronically P.c.-infected rats. They were killed after
      8, 12, 16, 20 or 24 weeks, and their lungs were examined for P.c. infection by
      means of light microscopy, immunohistochemistry and transmission electron
      microscopy. Lung lesions progressed from a mild interstitial pneumonia with
      scattered alveolar macrophages (8 weeks) to a severe diffuse interstitial
      pneumonia with widespread areas of distended alveoli, filled with foamy material.
      In all lungs, P.c. antigen was detected immunohistochemically, developing from
      small intra-alveolar aggregations of organisms into large multifocal clusters.
      Ultrastructurally, P.c. trophozoites and cysts were seen attached to type I
      pneumocytes and lying free in the alveolar lumen. Chronic severe P.c. pneumonia
      (20 and 24 weeks) was characterized by masses of P.c. trophozoites in the alveoli
      and alveolar walls, extensive proliferation of type II pneumocytes and
      interstitial fibrosis. The easy and consistent horizontal transmission of
      spontaneous P.c. pneumonia to previously non-infected athymic Han:RNU and
      Han:NZNU rats and the similarity of the disease to human infection demonstrate
      both rat strains to be excellent models for studying pulmonary pneumocystosis of
      immunodeficient human patients.

PMID- 8300912
TI  - Basement membrane components in mammary tumours of the dog and cat.
AB  - The distribution of the basement membrane (BM) components, laminin, type IV
      collagen and type VII collagen were studied immunohistochemically in benign and
      malignant growths of the mammary epithelium of the dog and cat. Intact BMs were
      found in benign growths, but in well-differentiated malignant tumours they were
      generally discontinuous, and missing in poorly differentiated carcinomas. An
      increase in the histological grade of atypia was accompanied by a more marked
      disruption or fading of BM. Monoclonal antibody (LH 7.2) proved useful in
      demonstrating type VII collagen in tumours in which massive proliferation of
      blood vessels made the evaluation of BM features with antibodies to laminin and
      type IV collagen difficult. Type VII collagen is present in BM of the mammary
      epithelium but not under the endothelium of blood vessels; it may therefore
      enhance the value of BM markers as aids in the study of neoplastic progression.

PMID- 8300913
TI  - Brain damage caused by a captive bolt pistol.
AB  - The neuropathological changes produced by a captive bolt pistol are described.
      The primary wound track in the brain was similar to that inflicted by a weapon
      such as a .22 calibre rifle. However neural and vascular damage at a distance
      from the primary wound canal was much less severe and widespread after
      penetration of the low velocity captive bolt projectile due to the formation of a
      smaller temporary wound cavity by radial forces imparted to the parenchyma. These
      findings suggest that the use of a captive bolt pistol for euthanasia should be
      immediately followed by further actions to ensure that an animal is rendered
      permanently unconscious.

PMID- 8300914
TI  - Ovine bone-marrow stromal cell-dependent myelopoiesis.
AB  - Conditions for the development of ovine bone marrow stromal cell-dependent LTBMC
      (long term bone marrow cultures) are described. After the addition of freshly
      isolated allogeneic bone marrow cells to a fully developed adherent stromal cell
      layer, myelopoiesis in the absence of erythropoiesis was sustained for up to 6
      months. Macrophages and/or mast cells predominated in the later stages of all
      cultures. Stromal cell conditioned medium (SCM) and lymph node conditioned medium
      (LNCM) both support the development of a similar range of colony-forming cell
      (CFC) types in soft agar clonogenic assays, including multipotential-CFCs capable
      of development into more than two cell lineages, haemopoietic blast-CFCs
      (undifferentiated cells), mast-CFCs, macrophage-CFCs, eosinophil-CFCs and
      neutrophil-CFCs. However SCM supported the development of larger colonies
      containing more cells than those supported by LNCM. Furthermore SCM together with
      LNCM supported increased numbers of all colony types compared with the numbers
      supported by SCM or LNCM alone. In both liquid and semisolid agar cultures of
      bone marrow cells, SCM together with ovine interleukin-3 (IL-3) augmented the
      development of mast cells in particular, a cell type supported by IL-3 alone,
      whereas SCM together with ovine granulocyte-macrophage colony stimulating factor
      (GM-CSF) supported increased numbers of neutrophils and macrophages, which were
      cell types supported by GM-CSF alone. Bone marrow stromal cells and medium
      conditioned from these cells are therefore able to support myelopoiesis and the
      development of inflammatory cell types in culture. SCM in combination with IL-3
      or GM-CSF is able to amplify the development of particular cell lineages
      supported by either IL-3 or GM-CSF alone.

PMID- 8300915
TI  - A canine nephropathy resembling minimal change nephrotic syndrome in man.
AB  - In the dog, massive proteinuria and/or the nephrotic syndrome have been commonly
      associated with renal amyloidosis and membranous glomerulonephritis. Primary
      glomerulopathies associated with the nephrotic syndrome in man also include
      minimal change nephrotic syndrome and focal glomerular sclerosis. A 4-year-old
      Collie dog is described with clinical, histological, immunohistological, and
      ultrastructural findings similar to those which characterize the minimal change
      nephrotic syndrome (MCNS) in man.

PMID- 8300916
TI  - Pathological changes associated with equine arteritis virus infection of the
      reproductive tract in prepubertal and peripubertal colts.
AB  - The nature and extent of changes associated with equine arteritis virus (EAV)
      infection of the reproductive tract was documented in 21 prepubertal and 15
      peripubertal colts. This study was part of an investigation into the relationship
      between stage of reproductive tract maturity and susceptibility to the
      experimental establishment of persistent infection with EAV. After intranasal
      challenge with a field isolate of EAV, all colts developed clinical signs of
      equine viral arteritis (EVA) from which they recovered rapidly. Clinical signs
      during the acute phase consisted of fever, serous to mucopurulent ocular and
      nasal discharge, oedema of the limbs, scrotum or prepuce, scleral injection,
      conjunctivitis, icterus, cough, diarrhoea, stiff gait, lethargy, inappetence and
      depression. At necropsy, the most significant macroscopic lesions included
      excessive accumulation of fluid within the thoracic and abdominal cavities, lymph
      node enlargement and oedema of the reproductive tract. Colts killed 7 to 14 days
      after challenge had acute necrotizing vasculitis involving the testes,
      epididymides, vasa deferentia, ampullae, prostatic lobes, vesicular glands and
      bulbourethral glands. Vasculitis was characterized by striking fibrinoid necrosis
      of small muscular arteries with extravasation of erythrocytes and proteinaceous
      material into the media, adventitia and perivascular tissues. Colts examined on
      days 28-180 had lymphocytic and plasmacytic inflammatory cell infiltrates in the
      lamina propria and muscularis of the epididymides and accessory sex glands. The
      vascular lesions found during the acute phase of EAV infection contrasted with
      the multifocal lympho-plasmacytic infiltrates found within the parenchyma of the
      reproductive tract during the chronic phase. One peripubertal colt was found to
      be persistently infected with EAV 15 months after challenge. This colt had marked
      lympho-plasmacytic infiltrates in the ampullae at necropsy.

PMID- 8300917
TI  - Immunocytochemical demonstration of Coxiella burnetii antigen in the fetal
      placenta of naturally infected sheep and cattle.
AB  - Coxiella burnetii antigen was demonstrated immunocytochemically in the placental
      tissues of aborted fetuses from four cows and two ewes and from one full-term
      calf. Antigen was observed in cytoplasmic vacuoles of trophoblasts, especially
      along the base of the chorionic villi. Positive trophoblasts were of normal size
      or exhibited striking cytoplasmic enlargement. Antigen was also demonstrated in
      neutrophils, degenerated cells and extracellularly in the intervillous spaces.
      The chorioallantoic connective tissue, allantoic surface and fetal tissues were
      devoid of C. burnetii antigen. Ovine placentas showed strong coxiella-specific
      staining and histological lesions characterized by moderate to severe,
      multifocal, necrotizing and purulent inflammation. In bovine placentas, the
      number of immunopositive cells varied from few to moderate and changes were mild
      or absent. Placental vasculitis consisting of infiltrating mononuclear cells,
      neutrophils or eosinophils was observed in both of the ovine and two of the
      bovine fetuses. In addition, a few intravascular thrombi were observed in one
      ovine and one bovine placenta. Thus the ovine coxiellosis cases were associated
      with an abundant accumulation of C. burnetii antigen and with severe necrotizing
      purulent placentitis, whereas in bovine coxiellosis the lesions were mild or
      absent and the number of organisms demonstrated immunocytochemically was much
      smaller. These results suggest a relation between species, lesion severity and
      weight of infection.

PMID- 8300918
TI  - The effects of tick-borne fever on the susceptibility of ovine polymorphonuclear
      cells to P. haemolytica cytotoxin.
AB  - Tick-borne fever predisposes sheep to secondary infections by Pasteurella
      haemolytica. Polymorphonuclear (PMN) cells obtained from sheep 2 to 7 days after
      the onset of parasitaemia due to Cytoecetes phagocytophila, the causative agent
      of tick-borne fever, were significantly more susceptible in vitro to the
      cytotoxin of P. haemolytica than PMN obtained from age-matched control sheep.

PMID- 8300919
TI  - Effects of bafilomycin A1 and amiloride on the apical potassium and proton
      gradients in Drosophila Malpighian tubules studied by X-ray microanalysis and
      microelectrode measurements.
AB  - The intracellular distribution of potassium in Malpighian tubules from Drosophila
      larva was measured by electron probe X-ray microanalysis of freeze-dried
      cryosections. Application of amiloride alone to the haemolymph space had no
      effect on the intracellular potassium concentration in the region of intermediate
      cytoplasm (between the basal region of basal membrane infoldings and the apical
      brush border), whereas a potassium increase as well as a chloride increase was
      observed after simultaneous blocking of the potassium conductance of the basal
      membrane with barium. Injected bafilomycin and amiloride applied in the
      haemolymph caused an increase of the potassium content in the basal cytoplasm but
      not in the microvilli. In addition, the intracellular water portion was decreased
      by bafilomycin. pH measurements in isolated larval anterior tubules with proton
      selective microelectrodes showed that bafilomycin added to the bathing solution
      caused a decrease in intracellular pH. Addition of amiloride had no significant
      effect on intracellular pH, but the pH of the luminal fluid was decreased within
      1 min by 0.5 pH units. The amiloride-induced luminal pH decrease could be
      inhibited by the metabolic blocker KCN as well as by bafilomycin. Furthermore,
      removing potassium from the bathing saline caused a slow luminal acidification,
      which could be blocked by KCN. Our results support the hypothesis of a
      functionally coupled transport system in the apical membrane consisting of a
      bafilomycin-sensitive V-ATPase and a K(+)-dependent, amiloride-sensitive K+/H+
      exchange system.

PMID- 8300920
TI  - Seasonal changes in critical enzymes of lipogenesis and triacylglycerol synthesis
      in the marmot (Marmota flaviventris).
AB  - Fatty acid metabolism and triacylglycerol synthesis are critical processes for
      the survival of hibernating mammals that undergo a prolonged fasting period.
      Fatty acid synthase, fatty-acid-CoA ligase, diacylglycerol acyltransferase, and
      monoacylglycerol acyltransferase activities were measured in liver and in white
      and brown adipose tissue, in order to determine whether enzymes of lipogenesis
      and triacylglycerol synthesis vary seasonally during hibernation in the yellow
      bellied marmot (Marmota flaviventris). Compared with mid-winter hibernation,
      fatty acid synthase activity was higher in all three tissues during early spring
      when marmots emerged from hibernation and in mid-summer when they were feeding,
      consistent with the synthesis of fatty acids from the carbohydrate-rich summer
      diet. Fatty-acid-CoA ligase and diacylglycerol acyltransferase activities were
      highest in summer in white adipose tissue when triacylglycerol synthesis would be
      expected to be high; diacylglycerol acyltransferase activity was also high in
      brown adipose tissue during spring and summer. In liver, however, diacylglycerol
      acyltransferase specific activity was highest during hibernation, suggesting that
      triacylglycerol synthesis may be prominent in liver in winter. Monoacylglycerol
      acyltransferase activity, which may aid in the retention of essential fatty
      acids, was 80-fold higher in liver than in white or brown adipose tissue, but did
      not vary seasonally. Its dependence on palmitoyl-CoA suggests that a divalent
      cation might play a role in enzyme activation. The high hepatic diacylglycerol
      acyltransferase activity during hibernation suggests that the metabolism of very
      low density lipoprotein may be important in the movement of adipose fatty acids
      to brown adipose tissue and muscle during the rewarming that occurs periodically
      during hibernation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300921
TI  - Development of Na+ transport in the chicken colon.
AB  - To evaluate the developmental changes in colonic Na+ transport, Na, K-ATPase
      activity and the sensitivity of the short-circuit current to amiloride were
      investigated. The amiloride-sensitive short-circuit current which represents the
      electrogenic, amiloride-sensitive Na+ transport through Na+ channels, was not
      present in chicken embryos but rose significantly after hatching in chicks which
      were kept on a low-salt diet. Amiloride-sensitive short-circuit current increased
      gradually but the plateau was not reached during the first 15 days of life.
      Drinking of 0.9% NaCl totally inhibited the induction of amiloride-sensitive Na+
      transport. Na+, K(+)-ATPase activity increased during development but was not
      influenced by changes in salt intake. Na+ transport in chicken colon therefore
      undergoes profound developmental changes. The increase of Na+ transport reflects
      not only the adaptation of colonocytes to low salt intake but also the maturation
      of Na+ absorption in colon. The possible role of aldosterone in the adaptation to
      low-salt intake is discussed.

PMID- 8300922
TI  - Molecular detection of Borrelia burgdorferi in formalin-fixed, paraffin-embedded
      lesions of Lyme disease.
AB  - A system for the detection of a Borrelia burgdorferi (Bb)-specific gene segment
      in formalin-fixed, paraffin-embedded skin lesions is described. A nested
      polymerase chain reaction technique is used to selectively amplify in vitro a
      short segment of a Bb-specific gene recently described by Rosa et al. (J Infect
      Dis 1989: 160: 1018). The design of oligonucleotide primers for the amplification
      of a relatively short gene segment allows the successful analysis of DNA which
      has been altered by fixation in formalin. Using this technique, Bb-specific DNA
      was clearly identified in 8 of 12 specimens of erythema chronicum migrans and in
      1 case of lymphadenosis benigna cutis. These skin lesions are known to represent
      cutaneous manifestations of Lyme disease. Negative control reactions, using DNA
      from borrelial strains not related to Lyme disease, were negative. The system
      enables the dermatopathologist to identify Bb in routinely fixed clinical
      specimens and allows the rapid analysis of various skin diseases for which an
      association with Bb so far has only been hypothesized.

PMID- 8300923
TI  - Suction-induced basal cell cytolysis in the Weber-Cockayne variant of
      epidermolysis bullosa simplex.
AB  - In the Weber-Cockayne form of epidermolysis bullosa simplex (EBS-WC), trauma
      induces blisters which are confined to the palms and soles. Histologically, basal
      cell cytolysis is seen. We studied 6 patients with EBS-WC to determine the
      ultrastructural level at which artificially-induced suction blisters form.
      Blisters were raised by application of a suction blister cup to uninvolved
      forearm skin, the cup being connected to a negative pressure of 200 mm of
      mercury. The blisters were biopsied and examined by light and electron
      microscopy. On light microscopy, all biopsies showed marked vacuolization of
      keratinocytes in the lower two-thirds of the epidermis, and in all but one there
      was a cleavage plane through the basal keratinocytes. These findings were
      confirmed by electron microscopy in 4 patients. The separation through the basal
      cells is in contrast to the situation in normal individuals in whom cleavage
      occurs below the level of the basal cells, within the lamina lucida. Thus, even
      apparently normal skin from non-acral sites has the same structural abnormality
      as the affected acral sites in EBS-WC.

PMID- 8300924
TI  - The specificity of histopathology in erythroderma.
AB  - Conflicting views about the diagnostic value of skin biopsy in the investigation
      of erythrodermic patients are extant. The objective of the present study was to
      establish the frequency with which a correct diagnosis can be based on
      histopathological assessment alone. This was achieved by comparison of the
      "blinded" microscopic diagnosis with the final diagnosis (based on combined
      clinico-pathologic parameters and response to therapy). In a retrospective review
      of 56 skin biopsies from 40 patients with erythroderma, we found a positive
      correlation between the pathological diagnosis and the final diagnosis in 66%;
      furthermore, when the microscopic characteristics observed in different
      diagnostic categories were assessed, these proved to simulate those seen in
      conventional manifestations of the various underlying diseases but tended to be
      subtle in the setting of erythroderma. We conclude that, despite the homogeneity
      of the clinical expression of erythroderma, diagnostic histopathological features
      of the underlying disease are retained in the majority of cases.

PMID- 8300925
TI  - The spectrum of cutaneous disease in leukemias.
AB  - Cutaneous eruptions are frequent complications in the clinical course of patients
      with leukemia. Leukemia cutis is occasionally the cause of the eruption, but in
      many cases the lesions are nonleukemic. We have retrospectively selected all skin
      biopsies from patients with a computer-coded diagnosis of leukemia seen in the
      Stanford University Department of Pathology in the last 7 years, and separated
      these cases into the broad categories of acute myelogenous leukemia (AML), acute
      lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and chronic
      lymphocytic leukemia (CLL). We also analyzed separately those cases seen in
      patients treated with bone marrow transplantation from those treated with
      standard chemotherapy regimens. We found that leukemia cutis was seen frequently
      as the cause of lesions in patients with CML and CLL. In contrast, a wide variety
      of lesions were seen in patients with AML, including a greater number of
      infectious lesions, drug reactions, vasculitis, and lesions secondary to a
      hemorrhagic diathesis. In the bone marrow transplantation patients, graft vs host
      disease was usually the cause of skin lesions in those transplanted for CML and
      ALL, but again those patients with an underlying diagnosis of AML showed a wide
      variety of lesions including drug reactions, fungal infections and leukemia
      cutis. Finally, 6% of cases from patients with AML showed intraepidermal
      blistering disorders of various types, an association that has not been
      previously reported.

PMID- 8300926
TI  - Verrucous cysts: histopathologic characterization and molecular detection of
      human papillomavirus-specific DNA.
AB  - Verrucous cyst is an uncommon newly described benign epithelial cyst which may be
      associated with human papillomavirus infection. The purpose of this project was
      to study the clinicopathological features of verrucous cysts and to demonstrate
      human papillomavirus (HPV) by polymerase chain reaction (PCR) in these lesions.
      We have analyzed 5 examples of verrucous cysts: the age range of the patients was
      between 37-82 years and the most common locations were face and extremities.
      Clinically the lesions were interpreted as cyst (2), dermatofibroma (2) and basal
      cell carcinoma (1). Histopathologic examination of the biopsy specimens showed in
      all cases an intradermal infundibular cyst lined by a papillated and/or digitated
      epithelium with focal prominent hypergranulosis and irregular keratohyalin
      granules. Furthermore, numerous whorls of keratinocytes (so-called squamous
      eddies) were present within the squamous areas of the hyperplastic epithelium of
      the cyst, morphologically reminiscent of inverted follicular keratosis.
      Architectural and cytological features of malignancy were not present. Sections
      of paraffin-embedded tissue of the 5 verrucous cysts and of 5 "conventional"
      follicular cysts, infundibular type, were investigated for the presence of HPV
      DNA sequences by PCR using consensus primers. In all 5 cases of verrucous cysts,
      HPV-specific DNA sequences were detected, whereas all follicular cysts,
      infundibular type, were negative. These results support the concept that
      verrucous cysts can be added to the large spectrum of HPV-induced cutaneous
      neoplasms. Further studies are needed to identify the specified HPV-type in these
      distinctive benign cystic proliferations.

PMID- 8300927
TI  - Incidental acantholysis.
AB  - The incidental finding of microscopic foci of acantholytic dyskeratosis,
      reproducing the histological pattern of Darier's disease, has been the subject of
      a number of papers in the last few years. In contrast, the incidental finding of
      other types of acantholysis has not been mentioned in the literature. In the last
      5 years, we have noticed such a microscopic finding in 14 biopsy specimens (0.15%
      of our cutaneous specimens). they were from 13 patients (7 men and 6 women);
      their ages ranged from 37 to 79 years (mean, 63). Three lesions were located on
      the head, 7 on the trunk, and 4 on the limbs. The histological diagnoses were
      basal cell carcinoma (6 cases), keratoacanthoma (2 cases), psoriasis (2 cases),
      elastolytic granuloma, acral arteriovenous angioma, tinea corporis, and
      leukocytoclastic vasculitis (1 case each). The histological patterns of the
      acantholytic foci simulated pemphigus vulgaris (9 cases), superficial pemphigus
      (1 case), Hailey-Hailey disease (3 cases), and unclassifiable acantholysis (1
      case). None of the patients had familial or personal history of acantholytic
      disorders. We propose a classification of the primary acantholytic disorders
      based on both their acantholytic pattern and their clinical extent.

PMID- 8300928
TI  - p53 immunoreactivity in cutaneous PUVA tumors is similar to that in other non
      melanoma skin neoplasms.
AB  - Expression of the p53 tumor suppressor gene product was determined in keratoses
      and skin cancers associated with psoralen photochemotherapy (PUVA). An
      immunocytochemical study was employed using CM-1 (polyclonal) and Do-1
      (monoclonal) antibodies to human wild-type p53. Thirty-two cutaneous lesions and
      20 perilesional PUVA-irradiated skin biopsies were examined from 7 patients, all
      of whom had received more than 200 PUVA treatments and/or a cumulative UVA dose
      of greater than 1000J/cm2 as treatment for widespread plaque psoriasis. p53
      immunoreactivity was seen in 7 of 15 squamous cell carcinomas (46.7%), 5 of 8
      dysplastic keratoses (62.5%) and in no basal cell carcinomas or benign keratoses.
      The overall prevalence of p53 immunoreactivity in 46.2% of malignant or
      dysplastic PUVA-associated skin tumors is similar to that previously found by our
      group in comparable skin tumors from the general population. Most patients with
      lesions showing positive p53 immunoreactivity had, however, been exposed to
      additional risk factors before receiving PUVA therapy. p53 gene sequencing of
      PUVA-associated non-melanoma skin cancer (NMSC) may clarify whether p53 mutation
      contributes to the development of these tumors and whether this relates to PUVA
      therapy or prior carcinogen exposure.

PMID- 8300929
TI  - Human papillomavirus DNA in the dermis of condyloma acuminatum.
AB  - Condyloma acuminatum (CA) has high recurrence rates after local treatments. Why
      this lesion is difficult to eradicate is unclear. One possible explanation for
      recurrence after superficial destructive therapy is the presence of residual
      human papillomavirus (HPV) in the superficial dermis beneath the treated
      epidermis. Thirteen samples of CA were excised from 13 patients. Thirteen samples
      of basal cell carcinoma (BCC) were studied for purposes of control. Epidermis was
      separated from dermis by treatment with sodium bromide. DNA was extracted from
      both tissues and used sodium bromide solution and amplified for the presence of
      HPV DNA using the polymerase chain reaction. HPV DNA was detected in the
      epidermis of 11 samples of CA. HPV type 6 was seen in 7 specimens; HPV type 11,
      in 4. HPV DNA was found in the dermis of 3 specimens of CA; type 6 in 2 and type
      11 in 1. Two samples were excluded because of contamination of the sodium bromide
      solution by HPV. HPV DNA was not detected in tissue samples from BCC. The
      presence of HPV DNA in the dermis of some condylomata may explain recurrence in
      sporadic cases.

PMID- 8300930
TI  - Giant cell fibroblastoma with dermatofibrosarcoma protuberans-like
      transformation.
AB  - A giant cell fibroblastoma (GCF) presented in the subcutis of the breast in a 13
      month-old girl which recurred 6 years later as a dermal and subcutaneous neoplasm
      whose patterns were in part GCF and spindle cells with a storiform configuration
      resembling dermatofibrosarcoma protuberans (DFSP). The issue remains unsettled as
      to whether GCF is the juvenile variant of DFSP, but an argument about this
      relationship is supported circumstantially by a case such as ours.

PMID- 8300931
TI  - Cutaneous metastasis of neuroendocrine carcinoma of uterine origin.
AB  - We report a case of a 33-year-old woman who presented with the rapid development
      of multiple dermal and subcutaneous nodules on the chest, back, abdomen, axilla,
      neck, and scalp. These nodules were firm, tender, and non-ulcerated and measured
      from 0.2 to 1.2 cm in diameter. A punch biopsy of one of the subcutaneous nodules
      in the scalp showed a poorly differentiated carcinoma in the reticular dermis
      with light microscopic, immunohistochemical, and ultrastructural features
      supporting neuroendocrine differentiation. The past medical history was
      significant for a recent total abdominal hysterectomy for carcinoma of the cervix
      at another hospital, originally characterized as a poorly differentiated
      adenocarcinoma of the cervix and lower uterine segment. Review of the microscopic
      slides of the uterine neoplasm revealed features suggesting a more appropriate
      classification as a primary neuroendocrine carcinoma; this was subsequently
      confirmed by immunophenotyping and ultrastructural evaluation. This is the first
      reported case of a uterine neuroendocrine carcinoma metastasizing exclusively to
      the skin. It further illustrates the important contribution of dermatopathology
      to the understanding of a systemic pathologic process.

PMID- 8300932
TI  - Malignant melanoma arising in a blue nevus with features of pilar neurocristic
      hamartoma.
AB  - A 65-year-old man presented with a history of a giant blue plaque of the parietal
      scalp since childhood. Biopsy revealed a cellular blue nevus. The blue nevus was
      observed for 10 years and thought to be unchanged until a new adjacent lesion was
      noted. Biopsy of the new lesion revealed metastatic malignant melanoma. A wide
      excision was performed of the original lesion which revealed malignant melanoma
      arising in a blue nevus. Areas within the blue nevus were consistent with a pilar
      neurocristic hamartoma, whereas other areas were consistent with a common blue
      nevus. Subsequent satellite metastases developed, with early metastases
      resembling blue nevi except for the absence of a stromal component and the
      presence of hyperchromatic nuclei. Later metastases were typical of metastatic
      melanoma. This case illustrates the uncommon evolution of malignant melanoma from
      a blue nevus. The histological features and relationship between melanoma, blue
      nevus, and pilar neurocristic hamartoma are reviewed.

PMID- 8300933
TI  - AADS 71st Annual session and exposition--Comimetment to Competence. Seattle,
      Washington, March 12-15, 1994. Program and abstracts.

PMID- 8300934
TI  - Lipid modification during epidermal cell differentiation.
AB  - As keratinocytes differentiate into corneocytes of the stratum corneum or
      epidermal permeability barrier, their lipids are modified so as to fulfill
      totally different functions. Recent experimentation has clarified the molecular
      mechanisms by which lipids of membrane origin are targeted to specialized
      lamellar bodies, where metabolic retailoring makes them suitable for use in the
      water-impermeable intercellular lamellae. In this latter structure the modified
      lipids are bound covalently to specialized proteins in a way that encourages the
      formation of lipid bilayers alternating with lipid monolayers. Only now are
      potential clues to the molecular regulation of this dramatic lipid transformation
      becoming apparent.

PMID- 8300935
TI  - Historical aspects of the oral use of retinoids in acne.
AB  - A number of investigations of the effects of vitamin A deficiency in animals and
      man and its treatment with natural products containing vitamin A were carried out
      in the twenties and thirties. In 1942, a clinical study in patients with acne
      treated with vitamin A yielded encouraging results. Further trials in the forties
      and fifties, trying to confirm the beneficial effect of oral vitamin A in acne,
      met with equivocal success. In the sixties, all-trans retinoic acid (tretinoin)
      became clinically available, and its topical efficacy in acne could be
      demonstrated. In 1971, oral tretinoin also was shown to be active in patients
      with acne. Coincidentally, the efficacy of oral 13-cis retinoic acid
      (isotretinoin) became evident in a series of unpublished studies in Europe. Then,
      in 1978, a trial carried out at the NIH, Bethesda, Maryland, yielded convincing
      evidence that isotretinoin is a potent new drug for the treatment of severe
      cystic acne. In 1982, isotretinoin was registered in the United States and one
      year later in Europe for the treatment of severe, recalcitrant, cystic acne.
      Since then, many thousands of patients suffering psychologically and physically
      from the severity of their disease have been treated successfully with this drug.
      However, the main concern of physicians prescribing isotretinoin has to focus on
      its potentially severe side effects, particularly its teratogenicity.

PMID- 8300936
TI  - Increased incidence of antismooth muscle antibody in Korean vitiligo patients.
AB  - To evaluate the incidence of autoimmune disorders and organ-specific
      autoantibodies in Korean vitiligo patients, antibodies to nuclear, mitochondrial,
      smooth muscle, gastric parietal cell, thyroglobulin, and microsomal antigens were
      screened in 226 vitiligo patients and 120 controls. Of the 226 vitiligo patients,
      three (1.3%) had thyrotoxicosis and two (0.8%) had diabetes mellitus. The
      vitiligo patients had an increased incidence of antinuclear (12.4%),
      antimicrosomal (7.1%), and antismooth muscle antibodies (25.7%). The increased
      incidence of antismooth muscle antibody was correlated with early onset (less
      than 15 years), a positive family history of vitiligo, and long duration of
      vitiligo. These results support an autoimmune origin of vitiligo and suggest that
      the high incidence of antismooth muscle antibody is a distinctive feature of
      laboratory findings in Korean vitiligo patients.

PMID- 8300937
TI  - Dispersed cell culture of human sweat duct cells under serum-free conditions.
AB  - Human eccrine gland duct cells were successfully cultured using a serum-free
      medium, K-GM medium. Eccrine sweat ducts were isolated from dispase treated skin
      specimens from palms or soles. After treatment of the isolated ducts with trypsin
      and EDTA, dispersed cells were cultured in K-GM medium. In primary cultures,
      small colonies were seen 3 to 4 days after inoculation. Then the cells rapidly
      proliferated and formed large colonies with a paving stone-like cell arrangement.
      During the culture, small dome shaped areas were sometimes formed in the centers
      of colonies. Cultures multiplied for a maximum of 7 passages. The plating
      efficiencies of the 1st to 6th passage cells were about 20% to 30%.
      Immunocytochemically, cultured cells were positively stained with anti
      carcinoembryonic antigens, K8.37 and K8.13, but not with anti-S100 protein, anti
      HLA-DR, 34 beta B4, or PKK3. An electron micrograph of the cultured cells showed
      a multilayer of flattened cells linked by desmosomes. These results indicate that
      the cultured cells possessed the staining properties compatible with those of the
      ductal portion of eccrine sweat glands. No contamination by other mesenchymal
      cells, such as fibroblasts, was seen during the culture.

PMID- 8300938
TI  - Ultrastructural observation of epithelioid sarcoma.
AB  - Epithelioid sarcoma located in the right hip-to-thigh region of a 58-year-old
      female was studied by light microscopy, immunohistochemistry, and electron
      microscopy. Light microscopy revealed both light and dark cells among the tumor
      cells. Round, homogeneous, eosinophilic bodies were noted extracellularly and
      intracellularly. Extracellular bodies were similar in size to tumor cells and
      were not stained by PAS or Congo red. In contrast, intercellular bodies were PAS
      positive and diastase resistant. Tumor cells were positive for vimentin, keratin,
      and, partially, for epithelial membrane antigen. Ultrastructurally, tumor cells
      had numerous microfilaments with tonofibril-like arrangement, lipid droplets, and
      reticulogranular structure in their cytoplasm. The reticulogranular structure was
      similar to the tonofilaments recognized in degenerative tumor cells. Oval
      filamentous bodies were recognized in the stroma. They appeared to be very
      similar to colloid bodies derived from tonofilaments of keratinocytes. It was
      considered that the filamentous bodies corresponded to extracellular eosinophilic
      bodies and showed signs of fibrous necrosis of tumor cells. Intracellular
      eosinophilic bodies were considered to be lipid droplets.

PMID- 8300939
TI  - A case of a giant schwannoma on the extremities.
AB  - A 52-year-old Japanese female with a human head sized lump on the medial femoral
      region of her right thigh is described. The histopathological diagnosis after the
      excision of the tumor was an ordinary type of schwannoma composed of two types of
      tissue, Antoni types A and B. The tumor was 20 x 15 x 12 cm in size and 2250 g in
      weight; this is probably the biggest of all the reported cases of schwannoma on
      the extremities in Japan.

PMID- 8300940
TI  - Fibroma of tendon sheath with ulceration.
AB  - We describe a 44-year-old man with fibroma of tendon sheath. The tumor originated
      in the foot and developed an ulcer during its course. It was totally excised, and
      the defect was reconstructed by full-thickness skin graft. The patient has been
      free of any recurrence during the follow-up period of one year. Fibroma of tendon
      sheath rarely occurs in the foot, and, to our best knowledge, this condition with
      ulceration is the first case reported.

PMID- 8300941
TI  - Spontaneous contraction of leukodermic patches in Waardenburg syndrome.
AB  - Waardenburg Syndrome is an autosomal dominantly inherited disorder with variable
      penetrance. It is a rare disorder with an estimated frequency of 1:20,000 in
      Kenya (East Africa) and 1:40,000, in the Netherlands presenting with or without
      deafness. The frequency with deafness is lower, estimated at 1:50,000 to
      1:212,000. The major characteristic features are as follows, with reported
      incidences in parenthesis: 1) Dystopia canthorum (99%); 2) synophrys (17%-69%);
      3) broad nasal root (78%); 4) depigmentation of hair, skin, or both (17%-58% with
      white forelock); 5) heterochromic or hypochromic irides (greater than 20%); 6)
      congenital deafness (9%-38%). Genetic heterogeneity has led to classification of
      affected families as type I, with dystopia canthorum, or type II, without
      dystopia canthorum (2, 6). Piebaldism and Woolf's Syndrome can present with
      pigmentary changes which are similar to Waardenburg Syndrome. Woolf's Syndrome
      also includes deafness. However, the distinguishing structural ophthomologic
      abnormalities of dystopia canthorum, broad nasal root, and synophrys are not
      found in either piebaldism or Woolf's Syndrome. The congenital patterns of
      leukoderma in both piebaldism and Waardenburg Syndrome has been believed to be
      stable throughout the lifetime of the affected individuals. We report an
      otherwise typical family with Waardenburg Syndrome, type I, in which 2 members
      atypically demonstrate spontaneous pigmentation and contraction of congenital
      leukodermic patches. To our knowledge, this has not been previously reported in
      Waardenburg Syndrome.

PMID- 8300942
TI  - Folliculosebaceous cystic hamartoma associated with rosacea.
AB  - A case of folliculosebaceous cystic hamartoma associated with rosacea is
      presented. Clinically, a solid, 5-mm-sized nodule was observed on the nose which
      showed telangiectasia and a waxy appearance. Histologically, a large horn cyst
      was located in the dermis, and was continuous with the surface epidermis. It was
      associated with mature sebaceous glands and immature hair follicles.
      Folliculosebaceous cystic hamartoma and similar cases have recently been
      reported, but this is the first report accompanied by rosacea.

PMID- 8300943
TI  - Acral ichthyosiform mucinosis in association with Sjogren's syndrome: a peculiar
      form of pretibial myxedema?
AB  - Two Japanese women developed well-demarcated ichthyosiform plaques on the lateral
      aspect of their lower legs. Deposition of mucin was demonstrated throughout the
      papillary dermis, unlike the site of mucin deposition seen in pretibial myxedema.
      Their thyroid function was normal. The condition of both women was complicated by
      Sjogren's syndrome. One of them who presented with positive anti-microsomal and
      anti-thyroglobulin antibodies had goiter, suggesting that her malady was also
      complicated by Hashimoto's thyroiditis. Their skin manifestations differed from
      those described in cutaneous mucinosis including pretibial myxedema, specifically
      with regard to the well-demarcated ichthyosiform appearance, the mucin deposition
      in the papillary dermis, and the association with Sjogren's syndrome. To the best
      of our knowledge, our cases may thus be considered to be a previously undescribed
      form of cutaneous mucinosis associated with Sjogren's syndrome.

PMID- 8300944
TI  - Dermatomyositis, carcinoma of colon and meningioma in the same patient.
AB  - Dermatomyositis and carcinoma of colon were diagnosed in a 66-year-old woman.
      Meticulous physical examination excluded further systemic or cutaneous
      involvement. The musculocutaneous disorders responded well to daily oral
      corticosteroid, and the malignant tumor was totally removed surgically. After a
      seven-year follow-up of actual dermatomyositis controlled by maintenance doses of
      prednisone ranging from 5 to 15 mg daily, the patient developed a meningioma.
      Current concepts and data regarding various aspects of the combination between
      dermatomyositis and tumors are discussed. To our knowledge, this is the first
      reported case of meningioma associated with dermatomyositis.

PMID- 8300945
TI  - High-dose tocopherol acetate therapy in epidermolysis bullosa siblings of the
      Cockayne-Touraine type.
AB  - We have employed a successful therapy for epidermolysis bullosa with high-dose
      oral tocopherol acetate. Two siblings with dominant dystrophic epidermolysis
      bullosa of the Cockayne-Touraine type were reported. Both siblings suffered from
      tense blisters and erosions healing with scars and transient milia on the
      extremities. Electron microscopic study of the blisters revealed a cleavage
      beneath the lamina densa in both siblings. High-dose oral tocopherol acetate
      therapy was administered to them with satisfactory clinical reduction of the
      blister formation.

PMID- 8300946
TI  - Keratoses following topical steroid for psoriasis.

PMID- 8300947
TI  - Behavioral measures of auditory thresholds in developing tree shrews (Tupaia
      belangeri).
AB  - The development of hearing in tree shrews (Tupaia belangeri) was tested through
      behavioral measures in the range of 0.3-60 kHz from the first postnatal
      thresholds detectable through to those of weanlings. The onset of hearing was
      defined using unconditioned startle responses, while, later on, pinna reflexes
      and head movements were used as behavioral indicators of sound perception.
      Startle responses could be evoked from day 16 after birth (DAB) onwards,
      indicating that the hearing system is capable of transferring airborne sound,
      although no reactions to tones were recorded at this age. The first unconditioned
      reactions to tones were found at DAB 18 in the range of 1-5 kHz (range of mother
      infant call). Responses were restricted to the range of greatest sensitivity in
      adults (1-10 kHz). An increase in sensitivity was detected from DAB 18-38. The
      lowest tested frequency (0.3 kHz) reached adult levels earlier than higher
      frequencies. No further improvement of auditory thresholds could be observed from
      DAB 38 (end of nutritional weaning) to DAB 42. Results were related to recent
      findings on the development of acoustical behavior and of the peripheral and
      central auditory system of tree shrews and other mammals.

PMID- 8300948
TI  - Vocal affect in three-year-olds: a quantitative acoustic analysis of child
      laughter.
AB  - Recordings were obtained of the laughter vocalizations of four 3-year-old
      children during three sessions of spontaneous free-play between mother and child
      in a laboratory playroom. Acoustic analysis was used to determine laughter
      durations, laughter events, F0, and harmonic characteristics, and to suggest a
      taxonomy of laughter types. Melodic contours were assessed from patterns of F0
      change during laughter. Mean duration of laughs ranged from 200 ms to 2.0 s, but
      events within a laugh were usually about 200-ms duration. Laughs were intuitively
      classified into four major types, and, following the acoustic analyses, were
      further defined and classified into types and subtypes of exclamatory and dull
      comment; chuckle; basic, variable, and classical rhythmical; and squeal. Melodic
      contours included more rising contours than previously reported for cry, but
      there was great variability in the types of contours produced especially for
      rhythmical laughs. The results of the acoustic analyses are discussed in relation
      to (a) the development of a taxonomy of laughter and (b) different features of
      the vocal affect characteristics of high-intensity emotion.

PMID- 8300949
TI  - Speaker-independent consonant classification in continuous speech with
      distinctive features and neural networks.
AB  - This paper provides experimental evidence to the assertion that the design of
      appropriate neural networks (NN) for speech recognition should be inspired by
      acoustic and phonetic knowledge, and not only by knowledge in pattern
      recognition. Rather than investigating the NN learning paradigm, the paper is
      focused on the influence of the input parameters, of the internal structure, and
      of the desired output representation on the classification performance of
      recurrent multilayer perceptrons. As an instructive example, the paper analyzes
      the problem of classifying ten stop and nasal consonants in continuous speech
      independently of the speaker. Experiments are reported for the TIMIT database,
      using 343 speakers in the training set and 77 different speakers in the test set.
      Comparative experiments show that good performance is obtained when many input
      acoustic parameters are used, including a time/frequency gradient operator
      related to transitions of the second formant, and when the desired outputs
      represent context-dependent articulatory features. Classification is performed by
      principal component analysis of the NN outputs. Refinement of the design
      parameters yield increasingly better performance on the test set, ranging from
      45% errors for a perceptron without hidden nodes to 23.3% errors for the best NN.

PMID- 8300950
TI  - Informational masking for multicomponent maskers with spectral gaps.
AB  - Simultaneous maskers comprised of a few random-frequency sinusoids can produce
      considerable informational (uncertainty-based) masking if the component
      frequencies are drawn from a wide range and changed with each stimulus
      presentation. The present experiments examined the effect on informational
      masking of removing masker energy from large frequency regions around the signal.
      Threshold for a 1000-Hz signal was measured in the presence of maskers comprised
      of 2, 4, 6, 10, 50, or 100 random-frequency sinusoids, notched-noise, or two
      fixed-frequency sinusoids. The multicomponent maskers had a maximum frequency
      range of 300-3000 Hz, typically excluding a 160-Hz band around the signal. In
      comparison conditions, masker frequencies were limited to the high or low side of
      the signal, or the gap around the signal was progressively widened. Four
      listeners showed substantial informational masking which was not eliminated even
      by extreme spectral gaps in the maskers. Four other listeners showed much smaller
      effects of masker uncertainty across all conditions. Notched-noise measures of
      auditory-filter width did not distinguish the two subject groups, but indices of
      processing efficiency were typically poorer for the high-threshold listeners, as
      were measures of both the width and processing efficiency of presumed
      "attentional filters" under conditions of masker-frequency uncertainty.

PMID- 8300951
TI  - Auditory filter shapes of normal-hearing and hearing-impaired listeners in
      continuous broadband noise.
AB  - Listeners with sensorineural hearing impairment typically exhibit auditory
      processing deficits such as reduced frequency and/or temporal resolution. Such
      deficits may represent separate sequela of auditory pathology or may result
      directly from the sensitivity loss and the requirement to listen at high levels.
      To assess the impact of increased thresholds on frequency resolution, auditory
      filter characteristics were determined for hearing-impaired and normal-hearing
      listeners at 500 and 2000 Hz in the presence of continuous broadband noise meant
      as a rough simulation of hearing loss. In the fitting procedure, the low
      frequency skirt of the derived auditory filter was allowed to vary as a function
      of signal level, permitting different filter shapes to be estimated at high
      versus low signal levels. Listeners with moderate hearing losses at 2000 Hz
      demonstrated near-normal auditory filter shapes for lower signal levels, but
      increasingly broad and asymmetric filters as signal level was raised. At 500 Hz,
      where hearing losses were mild, filter bandwidths increased little at the higher
      signal levels. The presence of broadband noise had essentially no effect on
      filter shapes of either listener group. The filter shape abnormalities
      demonstrated by listeners with moderate hearing loss, which were not observed in
      normal-hearing listeners at the same signal levels, indicate that poor frequency
      resolution in these patients for high-intensity stimuli does not follow directly
      from decreased sensitivity, but instead reflects an independent pathology.

PMID- 8300952
TI  - Spectral pattern and the perceptual fusion of harmonics. II. A special status for
      added components?
AB  - A single even-numbered harmonic can be segregated from an odd-harmonic complex
      more easily than its odd-numbered neighbors, for low fundamentals [Roberts and
      Bregman, J.Acoust. Soc. Am. 90, 3050-3060 (1991)]. It has been proposed that this
      effect occurs because the even harmonic is inconsistent with the regular spectral
      pattern formed by the odd harmonics. However, in this study we evaluate some
      alternative accounts of the effect. The stimuli were harmonic complex tones for
      which one of the components was cued by a preceding pure tone. Subjects were
      required to listen for the cued component and either to rate its clarity
      (experiments 1 and 3) or to judge its pitch in relation to the preceding tone
      (experiment 2). It is argued that the weaker fusion of an added even harmonic
      depends on its status as an added component rather than as an even harmonic
      (experiment 1), and on its immediate perceptual salience rather than on auditory
      learning. An even-odd difference was also found when even and odd harmonics were
      tested in an identical spectral context (experiment 2), and when one of the
      neighboring odd harmonics was removed (experiment 3). These results are
      consistent with the proposal that it is easier to segregate a harmonic from a
      periodic complex tone when it does not form part of the regular pattern of
      spectral spacing defined by the other harmonics.

PMID- 8300954
TI  - Self-suppression in a locally active nonlinear model of the cochlea: a
      quasilinear approach.
AB  - Mechanical input-output functions of the cochlea for pure-tone stimuli are
      nonlinear for frequencies around the characteristic frequency. To simulate these
      functions, a long-wave model of the cochlea containing a saturating pressure
      generator (located at the site of the outer hair cells) is solved in the
      frequency domain with a quasilinear method. In this method distortion products in
      the basilar-membrane (BM) response are treated as perturbations and the nonlinear
      pressure waveform is approximated by the first-order Fourier component. Because
      the saturating pressure generator forms part of a feedback loop the solution of
      the model is achieved in a number of iteration steps. Model results show
      flattening of the BM response at higher input pressures; this property, called
      self-suppression, is due to saturation of the pressure generator. The resulting
      input-output functions display the main features of experimental curves. The
      third-order distortion product in the BM velocity is always more than 25 dB below
      the primary BM velocity and does not influence the results of the computation;
      this justifies the use of the quasilinear method.

PMID- 8300953
TI  - Psychophysical and speech perception studies: a case report on a binaural
      cochlear implant subject.
AB  - Further improvements in speech perception for cochlear implant patients in quiet
      and in noise should be possible with speech processing strategies using binaural
      implants. For this reason, presented here is a series of initial psychophysical
      and speech perception studies on the authors' first binaural cochlear implant
      patient. For an approximate matching of the places of stimulation on the two
      sides, the patient usually reported a single percept when the two sides were
      simultaneously stimulated. Lateralization was strongly influenced by amplitude
      differences between the electrical stimuli on the two sides, but only weakly by
      interaural time delays. Speech testing, comparing monaural with binaural
      electrical stimulation, showed a binaural advantage particularly in noise.

PMID- 8300955
TI  - Auditory brain-stem response correlates of resistance to noise-induced hearing
      loss in Mongolian gerbils.
AB  - The auditory brain-stem response (ABR) was recorded from young adult Mongolian
      gerbils exposed to noise (octave band of noise centered at 4 kHz, 80 dB SPL, 6 h
      on, 18 h off) for 12 days. Temporary threshold shift (TTS) of 20-50 dB was
      measured at 4-8 kHz and TTS of 10 dB or less was measured at 1-2 and 16 kHz
      immediately after the initial exposure. Immediately following the final (12th)
      exposure, each animal had 10 dB or less threshold shift at all frequencies,
      demonstrating as much as 40-dB resistance to TTS. Because significant TTS was
      limited to the high frequencies, the apical portion of the cochlea was left
      relatively unaffected by the exposure. Amplitudes of waves ii-iii and iv of the
      ABR were unaffected at low frequencies and reduced at all stimulus levels for 8
      kHz on the first day of exposure; the amplitudes recovered to near-baseline
      levels by the 12th day of exposure. ABR latencies of waves ii and iv were
      prolonged at low stimulus levels on days one and six of exposure, but recovered
      to baseline levels by the 12th day of exposure. Because resistance to noise
      exposure was observed in all subjects and resistance was limited in spectrum, the
      results suggest that the gerbil is an excellent model for examining mechanisms of
      resistance to noise-induced hearing loss.

PMID- 8300956
TI  - The envelope following response (EFR) in the Mongolian gerbil to sinusoidally
      amplitude-modulated signals in the presence of simultaneously gated pure tones.
AB  - The envelope following response (EFR) is an auditory-evoked potential recorded
      from the scalp which is elicited by long duration, amplitude-modulated stimuli.
      In this paper, the results of a series of experiments exploring the behavior of
      the EFR elicited with sinusoidally amplitude modulated (SAM) tones in the
      presence of simultaneously gated, continuous, pure-tone interfering signals of
      varying intensity are reported. Probe stimuli consisted of SAM tones with
      carriers ranging in frequency from 800 Hz-4 kHz, modulated at frequencies between
      30-150 Hz. Probe signals were presented at intensities between 50 and 75 dB pSPL.
      Pure-tone interfering signals consisted of frequencies between 100 Hz and 10 kHz
      and ranged in intensity from -10 to +20 dB re: the probe. In these experiments a
      maximum reduction in the response to the probe tone, measured at the probe
      modulation frequency, appeared as a sharp peak within a narrow frequency band
      above the frequency of the probe carrier and a broader region of reduced response
      extending to higher frequencies. This reduction in response was asymmetrical,
      spreading more to high than to low frequencies. With an increase in the intensity
      of the interfering signal the maximum reduction of the response increased in a
      saturating, monotonic fashion with a concomitant broadening of the frequency
      region affected. The obtained interference response pattern may be attributable
      to both "synchrony capture" (i.e., capture of the EFR of the system by envelope
      components arising due to the interaction of probe and interfering signals) and
      "synchrony suppression" (i.e., a reduction in the synchronized response from
      neurons excited by the probe in the presence of the added interfering tone). It
      appears that the EFR to SAM stimuli of low to moderate intensity arose primarily
      from neuronal populations tuned to frequencies at or above the probe fc. The
      results of the present study suggest that at low intensity levels SAM signals are
      indeed relatively frequency specific and warrant further study for audiometric
      applications.

PMID- 8300957
TI  - Discharge suppression in the silent interval preceding the tone burst in pause
      build units of the dorsal cochlear nucleus of the unanesthetized decerebrate cat.
AB  - A recent intracellular study of dorsal cochlear nucleus (DCN) neurons in vitro by
      Manis [P. B. Manis, J. Neurosci. 10, 2338-2351 (1990)] suggests that the
      expression of the pause-build discharge pattern is in large part dependent on
      hyperpolarization of their membrane potentials in a period just preceding a
      depolarizing stimulus ("hyperpolarization conditioning" hypothesis). Our
      examination of the activity of a sample of pause-build units (n = 72) revealed
      suppression of discharge activity during a time window of the silent
      interstimulus interval (SII) just preceding the tone burst relative to the
      spontaneous rate in 74% of all units. The discharge suppression of a subset of
      DCN pause-build units in the SII satisfies a requirement of the
      "hyperpolarization conditioning" hypothesis, and thus supports the hypothesis.

PMID- 8300959
TI  - Doppler effect for sound emitted by a moving airborne source and received by
      acoustic sensors located above and below the sea surface.
AB  - The acoustic emissions from a propeller-driven aircraft are received by a
      microphone mounted just above ground level and then by a hydrophone located below
      the sea surface. The dominant feature in the output spectrum of each acoustic
      sensor is the spectral line corresponding to the propeller blade rate. A
      frequency estimation technique is applied to the acoustic data from each sensor
      so that the Doppler shift in the blade rate can be observed at short time
      intervals during the aircraft's transit overhead. For each acoustic sensor, the
      observed variation with time of the Doppler-shifted blade rate is compared with
      the variation predicted by a simple ray-theory model that assumes the atmosphere
      and the sea are distinct isospeed sound propagation media separated by a plane
      boundary. The results of the comparison are shown for an aircraft flying with a
      speed of about 250 kn at altitudes of 500, 700, and 1000 ft.

PMID- 8300958
TI  - Measures of auditory brain-stem responses, distortion product otoacoustic
      emissions, hair cell loss, and forward masked tuning curves in the waltzing
      guinea pig.
AB  - Measures of the auditory brain-stem response (ABR), distortion product
      otoacoustic emission (2f1-f2), hair cell loss, and forward masked tuning curves
      were obtained from waltzing guinea pigs and their age-matched controls at
      postnatal day 2, 9, 15, and 30. A mild ABR threshold shift (10-15 dB) is seen by
      2 days postnatal and gradually increases to a more severe threshold shift (40-50
      dB) by postnatal day 15. Already by 30 days the auditory brain-stem response,
      being beyond the output of the instrumentation, could not be elicited. The mean
      distortion product otoacoustic emission (DPOE) amplitude as a function of f1
      amplitude for the postnatal day 2, 9, and 15 waltzing guinea pigs were only
      between 3 and 8 dB below the control values for stimulus levels below 65 dB SPL.
      The DPOE audiogram constructed for the waltzing guinea pigs shows no more than an
      8-dB mean difference from the control values when the intensity of f1 was 50 dB
      SPL, and no more than 10 dB when f1 was 60 dB SPL. Analysis of the individual
      cases revealed that the DPOE amplitude could be greater than control values. On
      the contrary, when f1 stimulus levels were below 65 dB SPL, DPOEs could not be
      detected for the postnatal day 30 waltzing guinea pigs. At stimulus levels above
      65 dB SPL, DPOEs could be recorded yet these responses were depressed from
      control values by 10 to 25 dB. Analysis of surface preparations of the organ of
      Corti from the day 15 waltzing guinea pig reveals that the prominent alteration
      occurs on the third row outer hair cells. To a lesser extent, the second row
      outer hair cells, and then the first row outer hair cells are affected while the
      inner hair cells appear normal. In contrast, the organ of Corti from the
      postnatal day 30 waltzing guinea pig showed a more extensive outer hair cell loss
      among all three rows as well as a considerable degree of inner hair cell loss.
      Forward masked auditory brain-stem response tuning curves were generated at 8, 4,
      and 1 kHz for control and waltzing guinea pigs between 2 and 12 days of age. All
      tuning curves obtained from waltzing guinea pigs showed progressive decreases in
      sensitivity with increasing age. The Q 10 dB values of the 1- and 4-kHz tuning
      curves were not different between the controls and the waltzing guinea pigs at
      any age.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8300960
TI  - Adaptive feedback cancellation with frequency compression for hearing aids.
AB  - The use of an adaptive feedback canceler (AFC) for howling suppression in hearing
      aids seems very attractive since it is not only unaffected by the changes in the
      operating environment, but it also limits signal degradation due to the feedback
      signal. This, however, requires a reference signal which is correlated with the
      feedback signal but not with the input signal. In hearing aids, such a signal is
      hard to obtain. The output signal could be used as reference if its correlation
      with the input signal could sufficiently be removed. If the reference signal is
      correlated with the input signal, the input signal will also be canceled by the
      AFC. Here, the use of a frequency compressor as a decorrelator is proposed. The
      performance of this system is then investigated via digital simulation. Results
      indicated that with the use of the proposed system and the proper choice of
      system parameters, an increase of about 18 dB in the howling margin could be
      achieved with minimal deterioration in output signal quality.

PMID- 8300961
TI  - Comment on "Two-tone suppression of inner hair cell and basilar membrane
      responses in the guinea pig" [J. Acoust. Soc. Am. 93, 390-400 (1993)].

PMID- 8300962
TI  - A solution of the longstanding problem associated with discrete Fourier transform
      based, diffractive computation.

PMID- 8300963
TI  - Limited access to dissertations and theses.

PMID- 8300964
TI  - Postdoctoral education--a new tradition for nursing research.

PMID- 8300965
TI  - Regulation--when it is appropriate and when it is not.

PMID- 8300966
TI  - Whooooo are youuuuu?

PMID- 8300967
TI  - Nursing, quality, and work reorganization.

PMID- 8300968
TI  - Qualitative distinctions and similarities in the practice of clinical nurse
      specialists and nurse practitioners.
AB  - Current debate over whether clinical nurse specialist (CNS) and nurse
      practitioner (NP) roles should be combined or remain separate are largely
      theoretical. Minimal research has been conducted comparing these roles. Most
      studies to date consist of graduate follow-up surveys and comparisons of
      curricula. Interpretive results of Fenton's investigation of the practice of CNSs
      and Brykczynski's study describing the practice of NPs were compared to highlight
      the commonalities and distinctions between the two roles. This comparison is
      significant in that it explores the actual practice of CNSs and NPs. Both studies
      were modeled after Benner's research exploring the development of clinical
      expertise and produced adaptations of Benner's domains and competencies of
      nursing practice specifically for CNSs and NPs. Participant observations and
      small group interviews were the data-gathering methods used in these interpretive
      research studies. The interpretive approach is described as a situational,
      contextual, or narrative research method for understanding the knowledge and
      meanings in everyday (naturalistic) settings. Comparative analysis of results of
      the CNS and NP studies showed a shared core of advanced practice competencies as
      well as distinct differences between the practice roles. These findings have
      implications for curriculum development in advanced nursing practice.

PMID- 8300969
TI  - The basic nature of ethical problems experienced by persons with acquired
      immunodeficiency syndrome: implications for nursing ethics education and
      practice.
AB  - The purpose of this research was to describe and examine the basic nature of
      ethical problems that are experienced by persons with acquired immunodeficiency
      syndrome (AIDS). The participants were 25 persons with AIDS and 5 significant
      persons, not infected with the human immunodeficiency virus, who provided
      contextual understanding. The conceptual framework and method combined ethical
      inquiry and phenomenology. During an in-depth audiotaped interview, each
      participant answered the question, "What situation involving AIDS has caused you
      the most conflict about the right thing to do?" To assure scientific adequacy,
      the participant validated the analysis of the first interview in a second
      interview 2 weeks later, and five experts and two independent judges validated
      the combined analyses. From 117 ethical problems emerged a basic nature
      consisting of (1) conflict of values about what to believe, who to be, and what
      to do; (2) resolutions based on intuitive beliefs, desire to be a good person,
      and rational choice; and (3) rationale revolving around a desire for integrity
      and meaning. The findings suggest strategies for improving nursing ethics
      education and, ultimately, nursing practice: (1) base content on ethics research
      and philosophical analysis, (2) address real-life ethical problems, (3) discuss
      virtue ethics in addition to principled thinking and ethical caring, and (4)
      teach ethical listening.

PMID- 8300970
TI  - Professional values in baccalaureate nursing education.
AB  - The purpose of this study was to compare program objectives of National League of
      Nursing-accredited baccalaureate programs with the professional nursing behaviors
      that reflect the seven values identified by the American Association of Colleges
      of Nursing (AACN). Findings showed that most of the professional behaviors were
      found in program objectives. However, behaviors reflective of two essential
      values, truth and esthetics, were identified only in a minority of program
      objectives. In addition, research and life-long learning were overwhelmingly
      identified in program objectives, but they were not reflected in the professional
      nursing behaviors of the AACN document. The professional nursing behaviors were
      also classified according to the three major roles of baccalaureate graduates.
      The provider-of-care role was dominant, followed by the member-of-profession and
      coordinator-of-care roles.

PMID- 8300971
TI  - Difficult dialogues: impact on nursing education curricula.
AB  - Efforts to raise consciousness and heighten sensitivity toward the issues of
      races, class, ethnicity, and gender are being espoused throughout society today.
      Within higher education there is currently a national debate over whether or not
      curricula are exclusive of certain ethnic and cultural perspectives. The National
      League of Nursing (NLN) in 1989 resolved that innovative nursing curricula be
      developed that (1) enhance caring practices through faculty-student relationships
      and faculty-faculty relationships that are egalitarian and humane and
      characterized by cooperation and community building; (2) incorporate social
      values that recognize diverse life-styles and multicultural and multiracial
      perspectives; and (3) include contact with or participation by persons at risk
      including disenfranchised populations such as women, poor, elderly, and
      homosexual persons. The purpose of this article is to share two faculty members'
      experience of creating a "difficult dialogue" in a doctoral nursing education
      course. Generally speaking, difficult dialogues are encountered when academia
      attempts to include the experiences of white women, women of color, and men of
      color in the curriculum. The dialogues are difficult because engagement in this
      type of discourse may lead to feelings of discomfort and uneasiness among faculty
      and students. Although these feelings were experienced by class participants, the
      end result was a constructive and powerful learning experience. The willingness
      of the black students and faculty in the course to share their lived experiences
      of discrimination and oppression in a white society and the willingness of the
      white students and faculty to hear a different lived experience from their own
      was education at its best.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8300972
TI  - Role-taking abilities of nursing education administrators and their perceived
      leadership effectiveness.
AB  - This article examines the relationship between role-taking abilities of nursing
      education administrators and their perceived leadership effectiveness as rated by
      their faculty. Thirty nursing education administrators and their respective
      faculty members (n = 176) participated in this cross-sectional survey study. All
      participants filled out a demographic questionnaire, nursing education
      administrators also filled out the Davis Interpersonal Reactivity Index, which
      measured their role-taking abilities, and faculty also filled out selected
      subscales of the Leadership Behavior Description Questionnaire-XII (LBDQ-XII),
      which measured their perception of their nursing education administrators'
      leadership effectiveness. Correlation coefficients were calculated for these
      data, and they were also subjected to multiple regression analysis. Initial
      analysis of the data indicated that 26 of the 30 administrators were perceived to
      be effective leaders. Statistical analysis determined that there was a
      significant positive relationship between the role-taking abilities of the
      nursing education administrators and the consideration subscale of the LBDQ-XII.
      Multiple regression analysis found that certain organizational variables-
      formalization, centralization, and job satisfaction--affected the perception of
      leadership effectiveness. Further analysis of these three organizational
      characteristics according to large and small organizations found inverse
      relationships between job satisfaction and the faculty's perception of
      formalization and centralization. The results of this study support role-taking
      abilities among nursing education administrators as a way of enhancing their
      leadership effectiveness.

PMID- 8300973
TI  - Disability discrimination in nursing education: an evaluation of legislation and
      litigation.
AB  - The Americans With Disabilities Act of 1990, the Civil Rights Restoration Act of
      1987, and Section 504 of the Rehabilitation Act of 1973 have created rights for
      students with disabilities who choose to pursue an education in the health care
      disciplines. These statutes have also created new concerns for nursing educators
      as they assess students' qualifications for admission, retention, or dismissal.
      This article explores legislation and the judicial interpretation of the laws
      that affect disabled students in health care professions. Specifically, the
      article reviews and analyzes the reported case law in which health care students
      have claimed discrimination against education programs because of their
      disabilities. The analysis considers the requirements of the institution to
      assess or recognize if the student has a disability; to determine if the student
      is otherwise qualified to perform the essential responsibilities of the student
      role; and to establish reasonable accommodations for the student's learning
      environment. Finally, current and future implications for nursing education
      programs are presented.

PMID- 8300974
TI  - Gender differences in depression: perspectives from neuropsychology.
AB  - Although there has been much productive research in neuropsychology on the topic
      of depression, rarely has the issue of gender differences been taken into
      consideration. It is not uncommon for researchers investigating the
      neuropsychological concomitants of depression to test only women, or far more
      women than men, making it impossible to examine the prospect that there might be
      differences between these two groups. This article is an attempt to integrate
      research from two areas of neuropsychology: (1) gender differences in
      neuropsychological functions and (2) neuropsychological functions in depression.
      Since so few studies have examined gender differences in depression and their
      relation to neuropsychological patterns, there will be few firm conclusions to be
      drawn. However, some speculations will be offered, and some suggestions outlined
      for potentially fruitful future research.

PMID- 8300975
TI  - Puberty onset of gender differences in rates of depression: a developmental,
      epidemiologic and neuroendocrine perspective.
AB  - A dramatic feature of the epidemiology of depression is the appearance of a 2:1
      female excess of depression during adolescence. In childhood, rates of depression
      either do not differ between boys and girls or show a slight excess in boys. In
      this paper we review a number of lines of evidence that implicate the physical
      and hormonal developments of puberty in this change. We also argue that the
      analysis of pubertal change in the etiology of depression must take into account
      the fact that the causation of depression is almost certainly a complex process.
      In understanding such a process we suggest that developmental epidemiological
      studies will be of particular value.

PMID- 8300976
TI  - Do gonadal steroids regulate circadian rhythms in humans?
AB  - While a number of studies demonstrate that gonadal steroids regulate circadian
      rhythms in animals, the issue has received little attention in humans. The
      question is relevant to our understanding of gender differences in the
      phenomenology of depression, and of changes in the sleep-activity cycle that are
      seen in affective illness and during the menopause. In this paper, the literature
      demonstrating that gonadal steroids regulate circadian rhythms in animals is
      reviewed, along with the limited human literature. A hypothesis is forwarded
      suggesting that, in humans, estrogen shortens the circadian period, lengthens the
      sleep phase, advances sleep onset, and consolidates sleep. A study in progress is
      described which is designed to test the effects of the hypogonadal state,
      estrogen, and progesterone on circadian rhythms in women.

PMID- 8300977
TI  - Depression and weight gain: the serotonin connection.
AB  - The inability to control food intake and to engage in consistent exercise may
      account for repetitive episodes of weight gain. Many individuals who fail to
      maintain a normal weight may be susceptible to daily, monthly or seasonal
      perturbations in mood which result in an excessive intake of carbohydrate-rich
      foods and resistance to engaging in physical activity. Brain serotonin appears to
      be involved in these disturbances of mood and appetite; recent studies have shown
      that dietary and pharmacological interventions which increase serotoninergic
      activity normalize food intake and diminish depressed mood. Preventing recurrent
      weight gain may require periodic or sustained interventions that maintain mood
      and control over food intake.

PMID- 8300978
TI  - The menstrual cycle and mood disorders.
AB  - Greater attention to the possible effects of the menstrual cycle on the course of
      mood disorders in women has revealed that, at least for a subset of women with
      mood disorders, the premenstrual phase of the cycle may be a period of increased
      vulnerability for the appearance of a period of severe depression or for the
      worsening of an ongoing period of depression. The data supporting this conclusion
      and the implications for future research is summarized and discussed.

PMID- 8300979
TI  - Thyroid and adrenal measures during late pregnancy and the puerperium in women
      who have been major depressed or who become dysphoric postpartum.
AB  - Prior studies of thyroid, adrenal and mood measures during pregnancy and the
      puerperium, which we review, have not examined hormone-mood relationships over
      the full peripartum period during which hormone levels change nor have they
      compared prior depression history with hormone changes. In a pilot study we
      measured thyroid and adrenal hormones as well as mood at 38 weeks of pregnancy,
      and 1, 3, 6, 9 and 12 weeks postpartum in 12 women with major depression history
      and 14 women with negative psychiatric history. Subjects with prior depressions
      had significantly higher T3, T4, TSH and cortisol levels during the puerperium.
      Subjects with higher levels of postpartum dysphoria had lower T4 and free T4
      levels as well as higher T3 uptake at 38 weeks of pregnancy and higher cortisol
      levels during the puerperium. The pathophysiological implications of these
      findings are discussed.

PMID- 8300980
TI  - Sex differences in rates of depression: cross-national perspectives.
AB  - Rates of depression are compared by sex in epidemiologic surveys conducted in the
      United States, Canada, Germany and New Zealand. These surveys used similar
      sampling and diagnostic techniques and the data were standardized to the age and
      sex distribution of the USA to facilitate comparisons. Data show that the rates
      of major depression and dysthymia are higher in females than in males and are
      approximately equal for bipolar disorder across all four countries. The mean age
      of onset of major depression did not differ by sex across the four countries. The
      rates of major depression for males seem to be rising and for females stabilizing
      for birth cohorts born after 1945 (World War II). New data from the National
      Comorbidity Survey which has younger birth cohorts can directly examine this
      issue.

PMID- 8300981
TI  - Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence,
      chronicity and recurrence.
AB  - Basic epidemiologic prevalence data are presented on sex differences in DSM-III-R
      major depressive episodes (MDE). The data come from the National Comorbidity
      Survey (NCS), the first survey in the U.S. to administer a structured psychiatric
      interview to a nationally representative sample of the general population.
      Consistent with previous research, women are approximately 1.7 times as likely as
      men to report a lifetime history of MDE. Age of onset analysis shows that this
      sex difference begins in early adolescence and persists through the mid-50s.
      Women also have a much higher rate of 12-month depression than men. However,
      women with a history of depression do not differ from men with a history of
      depression in either the probability of being chronically depressed in the past
      year or in the probability of having an acute recurrence in the past year. This
      means that the higher prevalence of 12-month depression among women than men is
      largely due to women having a higher risk of first onset. The implications of
      these results for future research are discussed in a closing section of the
      paper.

PMID- 8300982
TI  - The role of gender-related processes in the development of sex differences in
      self-evaluation and depression.
AB  - This paper examines gender socialization processes during childhood that may
      contribute to a higher incidence of depression or depressive symptoms in females
      than in males. It is argued that because of the actions of socialization agents
      and the impact of gender stereotypes on a child's construction of gender
      identity, girls may exhibit higher levels of self-evaluative concerns that
      increase vulnerability to depression. Indeed, a review of the literature on sex
      differences in self-evaluation suggests that girls may be more susceptible than
      boys to self-evaluative concerns, particularly as reflected in lower expectations
      for future success, more maladaptive causal attributions for success or failure
      outcomes, and negative behavioral and evaluative reactions to failure. Moreover,
      an examination of the literature on sex differences in depressive symptoms leads
      to questions about previous conclusions that girls do not exhibit higher levels
      of depressive symptoms prior to adolescence. Finally, we present some recent
      original data that support the contention that sex differences in vulnerability
      to depression may be evident prior to adolescence.

PMID- 8300983
TI  - 43rd Annual Scientific Session of the American College of Cardiology. Atlanta,
      Georgia, March 13-17, 1994. Abstracts.

PMID- 8300984
TI  - Diet and breast cancer: more studies needed.

PMID- 8300985
TI  - Questions raised about LDL-C data.

PMID- 8300986
TI  - ADA applauds new FDA labeling rules that regulate health claims on dietary
      supplements.

PMID- 8300987
TI  - Battling morning (noon and night) sickness. New approaches for treating an age
      old problem. Interview by Nancy I. Hahn.

PMID- 8300988
TI  - Criteria that predict dietetics success. How to prepare students for coordinated
      undergraduate programs.

PMID- 8300989
TI  - Nutritional products for specific health benefits--foods, pharmaceuticals, or
      something in between?

PMID- 8300990
TI  - Evidence for a genetic influence on preference for some foods.
AB  - OBJECTIVE: The purpose of this study was to evaluate genetic influence on
      preference for 17 foods. The relationship between preference and use of these
      foods was also examined. The study focused on frequently eaten foods and on foods
      consumed less frequently but promoted for good health. DESIGN: Food preferences
      were investigated in young monozygotic and same-sex dizygotic twin pairs living
      at home and sharing the same environment. Subjects provided preference ratings
      after testing each food. A food frequency questionnaire was used to determine
      whether the genetic component of preference is associated with food use.
      SUBJECTS: Subjects were 14 pairs of monozygotic twins and 21 pairs of same-sex
      dizygotic twins, aged 9 to 18 years. They were recruited on a volunteer basis
      from public schools in Cincinnati, Ohio. MAIN OUTCOME MEASURES: We found a
      greater similarity in food preference between members of monozygotic twin pairs
      than between dizygotic twin pairs, which suggests an important role for genetics
      in accounting for individual differences in food preference. STATISTICAL ANALYSES
      PERFORMED: Food preference data were analyzed using Pearson correlation
      coefficients and Fischer z scores. Additional estimates of heritability were
      obtained by applying the Mann-Whitney nonparametric t test and the Holzinger
      index. Food use was correlated with preference using Pearson correlation
      coefficients. RESULTS: Significant differences in intrapair correlations for
      monozygotic and dizygotic twins were found for orange juice (z = 5.39; P < .05),
      broccoli (z = 2.60; P < .05), cottage cheese (z = 2.54; P < .05), chicken (z =
      2.54; P < .05), sweetened cereal (z = 2.00; P < .05), and hamburger (z = 1.95; P
      < .10). The genetic component of preference was correlated with use for only two
      foods. APPLICATIONS/CONCLUSIONS: It is important for nutritionists to realize
      that heritable factors may influence selection of a range of foods, including
      some that are promoted for good health. If health-promoting foods are to be
      included in the diet, accessibility and exposure to these foods must be
      increased.

PMID- 8300991
TI  - Impact of lactation on women with cystic fibrosis and their infants: a review of
      five cases.
AB  - OBJECTIVE: To evaluate the impact of lactation on the health status of women with
      cystic fibrosis and their infants. DESIGN: Data were acquired through a
      retrospective review of pulmonary, obstetric, and pediatric medical records.
      SETTING: A medical school-based Pediatric Cystic Fibrosis Center in Philadelphia,
      Pa. SUBJECTS: Five women with cystic fibrosis and their respective infants. MAIN
      OUTCOME MEASURES: For the women, measures of pregravid, gravid, and postpartum
      height, weight, pulmonary function test results, and energy intake were
      determined. For the infants, birth Apgar scores were obtained, as were measures
      of growth and development. STATISTICAL ANALYSES PERFORMED: Means and standard
      deviations were calculated. Data were compared with published standardized
      references. RESULTS: Mean maternal age at conception was 25.4 +/- 4.1 years. Mean
      pregravid weight was 60.0 +/- 10.7 kg of standard body weight for height (range =
      50.8 to 76.7 kg; median = 58 kg). Two women consumed up to two enteric-coated
      supplemental enzyme capsules per meal, three women consumed none. Pulmonary
      disease was mild in four of the five women. Mean weight gain during pregnancy was
      10.2 +/- 7.4 kg. Mean gestation was 37.4 +/- 1.5 weeks; mean birth weight was 3.0
      +/- 0.5 kg. Sweat tests performed on all infants were negative. Duration of
      breast-feeding was 3 to 30 weeks. Four of the five infants maintained appropriate
      growth velocity during breast-feeding. Mean maternal energy intake during
      lactation was above the Recommended Dietary Allowance for lactating women. Four
      of the five women were at or above their standard body weight during lactation.
      CONCLUSIONS/APPLICATIONS: We conclude that women with the clinical diagnosis of
      mild cystic fibrosis disease can maintain a normal pregnancy with appropriate
      weight gain and can deliver infants of normal weight for gestational age. During
      lactation, women with mild cystic fibrosis disease can maintain their own weight
      and support growth in healthy infants. The dietitian needs to be an integral
      member of the health care team in assessing, monitoring, and managing women with
      cystic fibrosis during their child-bearing years.

PMID- 8300992
TI  - Dietary fiber values for various breads are higher using enzymatic analysis
      rather than detergent analysis.
AB  - OBJECTIVE: To compare the dietary fiber content of breads commonly eaten in
      Georgia, Michigan, Nevada, and Vermont. DESIGN: Dietary fiber content was
      determined according to neutral detergent fiber (NDF) plus pectin values and
      enzymatic gravimetric fiber values. White, whole-wheat, 100% stone-ground whole
      wheat, cracked-wheat, and Roman Meal breads were analyzed for hemicellulose,
      cellulose, lignin, total NDF, pectin, and enzymatic gravimetric total fiber.
      STATISTICAL ANALYSES PERFORMED: Analysis of variance was used to determine
      significant F tests, and individual means were compared using Duncan's multiple
      range test. RESULTS: The 100% stone-ground whole-wheat bread had the most total
      fiber and fiber components followed by whole-wheat, Roman Meal, cracked-wheat,
      and white bread, except for pectin, of which Roman Meal had the most. The
      enzymatic gravimetric method of determining total fiber gave significantly (P <
      .0001) greater dietary fiber values than the values obtained by analyzing NDF
      plus pectin. These values ranged from 153% to 370% higher; however, there was a
      high degree of correlation (r = .95) between the methods. CONCLUSIONS: When
      recommending types of breads, dietitians should be aware of added ingredients
      that influence fiber values. When using published fiber values, dietitians should
      consider the technique used to quantify the fiber content.

PMID- 8300993
TI  - Validity and reliability of reported dietary intake data.
AB  - OBJECTIVE: To compare two training techniques for validity and reliability of
      dietary instruments and the measurement of total energy expenditure (TEE) to
      determine whether technique could influence the accuracy of food portion
      estimates. DESIGN: Adult women were randomized into a control group and an
      experimental group for comparison of training technique. SETTING: University and
      research center. SUBJECTS: Five hundred women were screened using the Three
      Factor Eating Questionnaire to identify restrained eaters or disinhibitors. Other
      criteria for selection included good health; absence of thyroid, respiratory, or
      other diseases; normal menstrual cycles; between the ages of 18 and 50 years.
      Forty-nine were recruited, with an attrition rate of 10% for a total sample of 44
      subjects. INTERVENTION: The control group (n = 26) was trained with food models
      and the experimental group (n = 18) was trained with a combination of food models
      and life-sized food photographs. All subjects completed two 24-hour recalls and
      14 consecutive days of food records. TEE was measured by the doubly-labeled water
      method. MAIN OUTCOME MEASURES: Training would improve the accuracy of food
      portion estimates. STATISTICAL ANALYSES PERFORMED: Analysis of variance, the
      paired t test, Pearson's correlation coefficient, and Wilcoxon's ranking test.
      RESULTS: The mean reported intake between instruments was found to be reliable;
      however, the comparison with TEE was underreported by 21.4% and was thus
      nonvalid. Training technique made no difference in validity or reliability. Both
      training techniques improved the accuracy of food portion estimates; however,
      improvement was enhanced with food photographs. APPLICATIONS/CONCLUSION: The
      findings indicate that training can improve food portion estimates, and dietary
      instruments may provide reliable but nonvalid results.

PMID- 8300994
TI  - Direct economic benefits associated with dietetic internships.
AB  - OBJECTIVE: We explored the direct economic benefits of hospital dietetics
      departments sponsoring an internship for dietetics studies. DESIGN: Forty-five
      dietetics departments in US hospitals participated in a mail survey that involved
      comprehensive data collection procedures using three instruments, including
      activity logs recorded by 298 dietitians and interns. MAIN OUTCOME MEASURES:
      Direct benefits were defined as the net student labor provided to the department
      during routine and staff relief experiences that released professional labor for
      other work. Net student productivity during routine assignments was calculated by
      subtracting the time dietitians spent teaching during a typical work week from
      the amount of time dietetic interns spent performing professional services
      without direct supervision. Student productivity during staff relief rotations
      was calculated by multiplying the number of students assigned to this type of
      experience by the length of the rotation. RESULTS: While involved in routine
      learning experiences, dietetic interns provided a direct benefit. The difference
      between the time interns spent in independent, professional service in the
      departments and the time dietitians spent in activities designed specifically for
      teaching was a mean of 29 hours in favor of the students. All departments
      received a direct benefit from assigning dietetic interns to a staff relief
      rotation. The median number of weeks of student labor gained by the departments
      per year was 24. STATISTICAL ANALYSES: A paired t test was used to analyze the
      difference between the time dietitians devoted to teaching interns and the time
      students spent in independent, professional service in the departments. The
      difference was very highly significant (P < .001) APPLICATIONS: This study is a
      beginning step in objectively documenting positive outcomes associated with
      sponsoring a dietetic internship. It also represents a model that could be used
      by program directors to study the economic impact of their supervised practice
      program on the sponsoring organization.

PMID- 8300995
TI  - A university-community model for the integration of nutrition research, practice,
      and education.
AB  - A model to integrate nutrition research, practice, and education was
      conceptualized and implemented to enhance student learning opportunities. The
      model encourages partnerships between educators and practitioners by providing a
      mechanism for faculty researchers to work with community practitioners to
      identify applied research and education projects in which students can
      participate in the design, implementation, analysis, and reporting. Learning
      experiences are discussed in relation to the knowledge and performance
      requirements for entry-level dietitians as mandated by The American Dietetic
      Association. Faculty and community practitioner relationships to support student
      learning and goal attainment are described. The research, practice, and education
      model has particular application to other universities struggling to balance
      limited resources with increasing expectations for community-university
      partnerships, and expectations for excellent teaching and scholarship. Resources
      needed (ie, staff, support services, and physical facilities) to develop and
      implement the model are discussed. Finally, acquisition options such as shared
      resources and in-kind contributions are suggested.

PMID- 8300996
TI  - Nutrition support for glutaric acidemia type I.
AB  - Glutaric acidemia type I is a rare, autosomal recessive, inborn error of lysine
      and tryptophan metabolism. This disorder is caused by a defect in the
      mitochondrial enzyme glutaryl-coenzyme A dehydrogenase, resulting in permanent or
      episodic elevations of glutaric acid. Despite clinical variability, untreated
      children often experience progressive neurologic damage that frequently leads to
      death. Recent evidence suggests that a lysine- and tryptophan-restricted diet and
      pharmacologic therapy with oral riboflavin and L-carnitine may arrest the
      neurologic deterioration. Several cases of normal growth and development have
      been reported in children diagnosed and treated before neurologic insult. In this
      article, we review previously published experience with dietary and pharmacologic
      therapy and provide guidelines for nutrition support based on our experience of
      treating four affected children. We suggest that dietary restriction of lysine
      and tryptophan is a safe and potentially effective therapy for individuals with
      glutaric acidemia type I.

PMID- 8300997
TI  - Risk for drug-induced malnutrition is unchecked in elderly patients in nursing
      homes.

PMID- 8300998
TI  - Factors associated with breast-feeding prevalence and duration among
      international students.

PMID- 8300999
TI  - Dietary assessment of middle-income pregnant women during the first, second, and
      third trimesters.

PMID- 8301000
TI  - Sensory qualities and nutrient retention of beef strips prepared by different
      household cooking techniques.

PMID- 8301001
TI  - Challenging the future: impact of information technology on dietetics practice,
      education, and research.
AB  - As we look at our nation's drive for technological superiority, global
      interdependence, major demographic shifts, and changes in consumer values and
      expectations, it is obvious that these changes will have a profound effect on our
      profession. Our leaders must be direction setters, change agents, and mentors in
      helping our members understand the importance of becoming part of this
      information and technological revolution. Because people often cling to the
      security of the past, leaders will have to possess the ability to convince others
      that there is a need for change. We must assume the risks related to making
      today's critical decisions about the role of infotech to the future of our
      profession. As individual members and leaders, we must not deny the reality of
      the technology challenge.

PMID- 8301002
TI  - [Progressive hyperopia after radial keratotomy. A new etiological hypothesis:
      early keratoconus].
AB  - As we routinely perform preop computer-assisted video-topography of the cornea in
      candidates for refractive surgery, we were able to recognize early keratoconus in
      more than 10% of the cases. Many undetected early keratoconus have been operated
      on in the 80's. We suggest a possible correlation between early keratoconus and
      increasing effect of radial keratotomy. The arguments of presumption are founded
      on clinical observations, knowledge about pathogenesis of keratoconus related to
      the mechanism of action of radial keratotomy, and epidemiologic considerations.

PMID- 8301003
TI  - [Bacteriological study of the intraocular fluid at the end of cataract surgery].
AB  - The authors studied bacterial contamination of the anterior chamber during
      extracapsular cataract extraction with intraocular lens implantation. A first
      study was conducted to determine the rate of contamination of anterior chamber
      aspirates, before surgery, in 46 patients undergoing cataract extraction. A
      second study concerned 200 patients undergoing extracapsular extraction with
      posterior chamber lens. Anterior chamber fluid was aspirated at the end of
      surgery, and inoculated into blood culture bottles. Bacteriological results were
      positive in 11 cases, and were compared with conjunctival smears. The way in
      which aqueous humor was aspirated and inoculated is described. The
      bacteriological method was tested with a small inoculum of bacteria.
      Bacteriological study of intraocular fluid at the end of cataract surgery might
      be useful in the diagnosis and treatment of postoperative endophthalmitis.

PMID- 8301004
TI  - [The Schocket tube. A retrospective study of 36 cases].
AB  - Thirty-six eyes with refractory glaucoma were operated using a Schocket technique
      (anterior chamber shunt to an encircling band). The follow-up was more than one
      year in all cases with a two-year maximum follow up. The intraocular pressure was
      < or = 25 mmHg in 87.5% to 95% of cases, and < 21 mmHg in 75.8% to 81.5% of
      cases. The results were analysed for each etiology and compared with those of
      other series and those of other surgical techniques used in the treatment of this
      type of glaucoma. (Molteno drainage tube, cyclodiathermy, ultrasonic treatment
      and yag laser transcleral contact cyclophotocoagulation).

PMID- 8301005
TI  - [Indications for penetrating keratoplasty. A retrospective study of 2,962 cases
      over 11 years].
AB  - The authors report the course of penetrating keratoplasty (PK) in a series of
      3,012 grafts performed at the Hotel-Dieu de Paris Ophthalmology Department from
      1980 to 1991; 2,962 cas (98.5%) could be analysed and were divided into 17
      etiologic groups. In the literature, Aphakic Bullous Keratopathy (ABK) and
      Pseudophakic Bullous Keratopathy (PBK) are usually considered to be the most
      frequent PK indication. In our series, they came in third place overall with 281
      cases (9.5%). Their incidence showed a constant increase over the study period,
      and they became the most frequent indication in 1991 (21.4% versus 6.8% in 1980).
      Keratoconus was the most frequent surgical indication with 813 cases (27.6%).
      This high percentage has been reported by other research groups. We explain our
      findings by a bias in the choice of corneal recipient candidates due to a
      tendency of the surgical team to give available donor corneas to patients with
      statistically higher chances of functional success. We also notice that corneal
      herpes sequelae, classically the leading cause of PK in the seventies, became the
      second indication overall and showed a decreasing tendency between 1980 and 1991.
      Finally, non herpetic leucomas (8.9%), graft failures (8.6%), and Fuchs dystrophy
      (8.3%) showed a constant PK indication rate throughout the study period.

PMID- 8301006
TI  - [Treatment of macular detachment complicating optic disk coloboma pits. Long-term
      results of the photocoagulation-gas combination].
AB  - We managed 19 eyes of 19 patients with serous macular detachment associated with
      optic nerve pits with photocoagulation of the temporal edge of the optic disc
      combined with intravitreal injection of an expanding gas. SF6 was used in 8 eyes,
      and C3F8 in 11 eyes at the initial treatment. Eight eyes (42%) had repeated
      treatment because of failed initial treatment and/or late recurrence(s). Eighteen
      patients were followed up for 4 to 110 months (mean follow-up: 39 months). At the
      last examination the macula was attached in 17 of 18 eyes (94.4%). However 3
      patients (17.6%) showed a limited serous retinal detachment distant from the
      macula. The results achieved after single treatment were better with C3F8 than
      with SF6 (78.5% versus 57% anatomical success rate). During the follow-up period,
      5 eyes (27.7%) developed one or two late recurrences. Macular reattachment
      occurred spontaneously in 2 eyes and after repeated C3F8 injection in 3 eyes. The
      final visual acuity was improved by 0.1 to 0.6 as compared to the initial visual
      acuity in 12 patients (66.6%). Ten patients (55.5%) had a final visual acuity >
      or = 0.5 and > or = Parinaud scale no. 2. We believe that photocoagulation
      treatment combined with C3F8 intravitreal injection is a valuable approach to the
      management of serous macular detachment associated with optic nerve pits. However
      the treatment also shows limitations, in particular the need for repeated
      treatment in failed eyes and/or eyes with late recurrences.

PMID- 8301007
TI  - [Role of nasolacrimal intubation in the treatment of lacrimation caused by
      congenital lacrimal duct obstruction in infants].
AB  - We report a study of a series of 83 cases of congenital nasolacrimal duct
      obstruction treated with monocanaliculonasal or bicanaliculonasal silicone
      intubation. Efficacy, complications, as well as the duration of the placement of
      the probes were studied. The analysis of the various factors of this series (age
      of the infants at the time of intubation, duration and type of intubation,
      complications) demonstrated the superiority of short-term monocanaliculonasal
      intubation (about four weeks) compared to longer intubation.

PMID- 8301008
TI  - [Ultrasonographic study of posterior vitreous detachment in emmetropic eyes].
AB  - Vitreoretinal relationships can be evaluated by biomicroscopic examination and
      ultrasound. We analyzed 220 normal and emmetropic eyes in a population between
      the ages of 20 to 80 years to evaluate the position of the posterior vitreous
      surface (prospective study). We found that: Most cases of very partial and very
      peripheral P.V.D. (71/220 eyes; 32%), especially those confined to the nasal
      quadrant (50/71 eyes), corresponded to a simple increase of reflectivity of the
      vitreous base rather to than real PVD. Twenty-five per cent of the patients over
      the age of 80 years did not have PVD. The frequency of partial PVD located in 2,
      3 and 4 quadrants except the posterior pole was very low, regardless of age.
      These partial PVD are transient. Fifty-eight per cent of the patients over the
      age of 80 years had a complete PVD. This percentage is clearly lower than that
      reported by most of the large biomicroscopic studies. The extension of PVD always
      begins at the vitreous base and ends at the posterior pole. This extension occurs
      around the age of 60-65 years and results, in most cases (35/38 eyes; 92%), in
      complete PVD with collapse. A prepapillary ring is a specific sign of complete
      PVD with or without collapse, but its absence (5/38 eyes) does not indicate the
      absence of PVD. The frequency of giant lacune is maximal (16/32 eyes; 50%) for
      young people between the ages of 30 and 40 years, then decreases as PVD becomes
      complete. The average level of reflectivity of the vitreous body is highest for
      patients between the ages of 70 and 80 years, but this variation is only very
      slight. This study also stresses the clinical criteria used to make the
      ultrasonic differential diagnosis between PVD and giant lacunae.

PMID- 8301009
TI  - [Anterior lenticonus and Alport's syndrome].
AB  - A case of anterior lenticonus is reported in a 26 year old man with hemorrhagic
      nephritis related to familial Alport's syndrome. Anterior lenticonus is seen only
      as a part of Alport's syndrome. The authors describe its clinical, histologic and
      therapeutic aspects. They also discuss the other ocular manifestations, the
      nephritis and the sensorineural deafness.

PMID- 8301010
TI  - [Choroid rupture, macular hole and subretinal neovessels following contusions].
AB  - We present a case of choroidal rupture of the fovea, progressing to a macular
      hole and sub retinal new vessels. Blunt trauma of the eye ball and the posterior
      pole can progress years after the initial trauma.

PMID- 8301011
TI  - [Cheloid nodule of the free edge of the eyelid].
AB  - Clinicopathological report of a keloid nodule of the eyelid arising apparently de
      novo in an 80 year old woman. Histopathologic and pathogenic discussion.

PMID- 8301012
TI  - [Penetrating keratoplasty].

PMID- 8301013
TI  - [Ablation of the posterior hyaloid in vitrectomy].

PMID- 8301014
TI  - [Inflammatory diseases of the limbus].

PMID- 8301015
TI  - [Treatment of internal limiting membrane retraction syndrome].

PMID- 8301016
TI  - Lithium in vitro enhances interleukin-2 production by T cells from patients with
      systemic lupus erythematosus.
AB  - Cellular immunity is impaired in patients with systemic lupus erythematosus
      (SLE). A decreased production of interleukin-2 by T cells isolated from blood of
      patients with SLE was found. The decrease correlated with severity of the
      disease. It was shown that incubation in vitro of T cells with 5 mM of lithium
      chloride augmented interleukin-2 production. The increase in cultures of T cells
      from patients with SLE was higher that than in healthy individuals. It is
      believed that lithium increases the cytosol inositol triphosphate level and
      subsequently augmented impaired intracellular signal transduction in the T cells
      from patients with SLE.

PMID- 8301017
TI  - Effect of ASTA-Z 7575 (INN Maphosphamide) on human lymphokine-activated killer
      cell induction.
AB  - Recent studies combining chemotherapeutic agents with various biological response
      modifiers for the treatment of cancer have shown promising results.
      Cyclophosphamide (Cy) is the most widely used alkylating agent and a major
      constituent of combination chemotherapy regimens for many neoplastic diseases. It
      has been reported that Cy is a cytotoxic drug, which becomes immunosuppressive at
      higher doses. A synthetic metabolite of Cy, ASTA-Z, has recently been produced.
      ASTA-Z is more active and stable by itself and does not need to be metabolically
      converted to an active compound. The combined effect of Cy and interleukin-2 (IL
      2) on the induction of lymphokine-activated killer (LAK) cells is not known.
      Therefore, we decided to investigate the effect of ASTA-Z on the induction and
      function of LAK. The coculture of peripheral blood mononuclear cells (PBMC) with
      various concentrations of ASTA-Z (0, 10(-6), 10(-5), 10(-4), and 10(-3) dilution)
      and IL-2 (50 U/ml) for 4 days produced significant suppression of cytotoxicity
      and lytic ability of the LAK cells against NK-sensitive (K562) and NK-resistant
      (M14) tumor cell lines. The lower doses of ASTA-Z did not affect the generation
      of LAK cells, its cytotoxicity and lytic ability of ASTA-Z against both NK
      sensitive and NK-resistant tumor cell lines. Furthermore, the ASTA-Z produced
      dose-dependent suppression of the proliferative response of LAK cells. The
      significant therapeutic benefit in the cancer patient may be achieved by the low
      dose regimen of Cy and IL-2 because it has no deleterious effect on the induction
      and function of LAK cells.

PMID- 8301018
TI  - Immunostimulant activity of a novel lipopeptide and its protective action against
      Leishmania donovani.
AB  - Novel lipopeptides 84/201 and 86/450 synthesized in this laboratory stimulated
      antibody and delayed type hypersensitivity (DTH) response to ovalbumin in guinea
      pigs. Lipopeptide 86/450 also stimulated antibody and DTH responses in albino
      mice and enhanced nonspecifically macrophage migration index (MMI), phagocytic
      activity and incorporation of [14C] glucosamine in peritoneal macrophages of the
      treated animals. Proliferative response of splenocytes from lipopeptide 86/450
      treated animals was significantly higher than that from untreated controls.
      Peritoneal macrophages from lipopeptide 86/450 treated mice were less susceptible
      to Leishmania donovani promastigote invasion when co-cultured in vitro. The
      treated animals on challenge with L. donovani promastigote/amastigote showed 80
      to 90% lower intake of infection than the control animals.

PMID- 8301019
TI  - In vitro inhibition of cellular immune responses by benzodiazepines and PK 11195.
      Effects on mitogen- and alloantigen-driven lymphocyte proliferation and on IL-1,
      IL-2 synthesis and IL-2 receptor expression.
AB  - In vitro mitogen-driven lymphocyte proliferation tests (Con A, LPS) on murine
      lymph node and spleen cells revealed inhibition of T and B cell stimulation by
      different benzodiazepines and by PK 11195, with IC50 values in the low micromolar
      range. T cell responses as a consequence of recognition of alloantigens, as
      measured in mixed lymphocyte cultures (MLC), were affected in an analogous way.
      In all systems, agonists at peripheral type benzodiazepine receptors (Ro 5-4864
      and the non-benzodiazepine compound PK 11195) and diazepam which acts on both,
      central and peripheral type benzodiazepine receptors, were most potent;
      clonazepam, a central type agonist, proved about half as active. The central type
      antagonist Ro 15-1788 failed to antagonize the action of diazepam and clonazepam.
      Variations among cells from several congenic strains of mice were modest.
      Cytotoxicity could not be made responsible for drug effects. The most susceptible
      stage of mitogen-triggered T and B lymphocyte proliferation was found to be at
      incipience. Radioresistant, adherent spleen cells, upon LPS-stimulation formed
      only small amounts of the cytokine IL-1. Its release was affected only at very
      high drug concentrations. Similar small amounts of IL-1 were generated during
      MLC; in this case, the drugs were about 10 times less potent than in mitogen
      induced proliferation assays. Peripheral agonists were more active on IL-1
      synthesis. Spleen cells stimulated with Con A and cultivated with the highest
      concentration of diazepam and clonazepam formed markedly greater amounts of IL-2
      than those cultivated in medium, while at this concentration PK 11195 allowed no
      formation of the lymphokine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301020
TI  - Influence of dietary aluminum on cytokine production by mitogen-stimulated spleen
      cells from Swiss Webster mice.
AB  - Swiss Webster mice were exposed to excess dietary aluminum (Al) (1000 micrograms
      Al/g diet, Al as Al lactate) from conception to 6 months of age. Splenic
      lymphocytes (10(6) per culture) were incubated for 24 hrs with concanavalin A (5
      micrograms/ml). Concentrations of interleukin-2, interferon-gamma and tumor
      necrosis factor-alpha, as measured in supernatants via ELISA with monoclonal
      antibodies, were depressed in spleen cells from aluminum treated mice relative to
      controls. Experiments using the fluorescence activated cell sorter demonstrated a
      shift in T-cell populations from treated mice with a deficiency of CD4+ cells.
      These findings suggest a deficit in immune effector cell function after long term
      in vivo aluminum exposure.

PMID- 8301021
TI  - Immunogenicity studies of a synthetic antigen of alpha methyl dopa.
AB  - Since the idiosyncratic liver toxicity of methyl dopa (L-alpha-methyl-3,4-
      dihydroxy-phenylalanine) may be due to immune mediated mechanisms, immunologic
      tools are needed to detect methyl dopa induced antibody and antigen. Hapten
      (methyl dopa)--carrier (albumin) conjugates were synthesized to generate
      antibodies reactive with this drug. Studies were also conducted to test the
      immunogenicity of this hapten-carrier conjugate and its cross reactivity with
      methyl catechol and levodopa. Methyl dopa (MD), levodopa (LD) or methyl catechol
      (MC) were conjugated to rabbit serum albumin (RSA) under high pH (base)
      conditions or by a tyrosinase (tyr) catalyzed reaction. Under the base
      conjugation conditions, MD-RSA, LD-RSA and MC-RSA conjugates were produced at
      higher hapten: carrier ratios than conjugates produced by the enzyme catalyzed
      reaction. Rabbits were subsequently immunized with either MD-RSA(base) or MD
      RSA(tyr). Antibodies elicited by MD-RSA(base) had marked reactivity to the
      carrier protein, albumin, whereas antibodies elicited by MD-RSA(tyr) did not. In
      addition, reactivity of anti-MD antibody was equal to or greater with MC-RSA than
      reactivity with either MD-RSA or LD-RSA. This work suggests that the conjugation
      method using the tyr catalyzed reaction produces the optimal immunogen with
      minimal modification of the carrier protein. In addition, the catechol moiety of
      MD, MC and LD appears to be the immunogenic epitope on these haptens.

PMID- 8301022
TI  - Differential modulation of contact hypersensitivity and delayed hypersensitivity
      reactions by topical application of 12-O-tetradecanoylphorbol-13-acetate.
AB  - Ear/footpad swelling following sensitization and challenge with 2,4
      dinitrofluorobenzene (DNFB)/allogenic splenocytes (AS) were used to monitor the
      effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on contact hypersensitivity
      (CHS) and delayed hypersensitivity (DHS) reactions, respectively. Topical
      treatment of dorsal or ventral SENCAR mouse skin 4x with 2 micrograms of TPA
      prior to sensitization of dorsal skin with DNFB suppressed attempts to induce CHS
      by subsequent challenge with DNFB. The adoptive transfer of splenocytes isolated
      from mice pretreated on the dorsum with TPA prior to dorsal sensitization with
      DNFB inhibited the development of CHS to DNFB in recipient mice. Conversely,
      topical treatment with TPA prior to s.c. sensitization with AS neither suppressed
      subsequent attempts to induce DHS, nor resulted in the generation of a splenocyte
      population capable of suppressing DHS reactions in adoptive transfer studies.
      Thus, promoting doses of topically applied TPA has differential effects on CHS
      and DHS reactions.

PMID- 8301023
TI  - Alzheimer's caregivers. Psychosocial support via computer networks.
AB  - 1. An important role of the nurse as coordinator of geriatric client care is to
      provide psychosocial support (emotional, spiritual, and informational) to family
      members. 2. In order to fulfill this role, nurses must avail themselves of new
      and creative technologies, such as computer networks. 3. A community computer
      network, ComputerLink, has helped to meet the emotional, spiritual, and
      informational needs of caregivers of Alzheimer's disease patients.

PMID- 8301024
TI  - Near falls incidence. A study of older adults in the community.
AB  - 1. Although falls in older adults have been studied in a variety of settings,
      near falls (or almost falling) have received little or no attention--and
      therefore their clinical relevance is unknown. 2. Older adults were able to
      discriminate between near fall and actual fall events without difficulty. 3.
      Thirty-five percent of the older adults who participated in this study
      experienced near falls in the 3-weeks of data collection. Therefore, near falls
      are common events in the lives of many older adults.

PMID- 8301025
TI  - Patient Self-Determination Act. Implementing an information program in a nursing
      facility.
AB  - 1. Several legal landmarks regarding the withdrawal or refusal of life-sustaining
      treatments led to the development of advance directive documents. Advance
      directive documents allow an individual to indicate preference for medical
      treatment while he or she is capable. 2. The Patient Self-Determination Act
      (1991) was enacted to ensure that patients are advised of their right to accept
      or refuse medical care, and to promote the right to execute an advance directive.
      3. Implementing an information program about advance directives in a nursing
      facility requires an understanding of the process of change.

PMID- 8301026
TI  - Gerontological caregiving: analysis of family experience.
AB  - 1. Regardless of gender, caregivers readily relinquish personal activities in
      order to perform caregiving tasks. 2. Caregivers seldom solicit assistance from
      other family members. 3. Caregivers experience difficulty balancing caregiving
      with outside employment and significantly reduce work hours or cease employment
      altogether.

PMID- 8301027
TI  - A systemic window: revelations of aging.

PMID- 8301028
TI  - A survey of gerontological curricula in Canada generic baccalaureate nursing
      programs.
AB  - 1. This study surveyed the status of gerontological curricula in the Canadian
      generic baccalaureate nursing programs--and the opinions of provincial "experts"-
      on the requirements of gerontological nursing to determine how nurses are or
      should be prepared to meet the health care needs of aging Canadians. 2. Questions
      were formulated to explore the following issues: nursing models used by the
      schools, faculty preparation, integration of gerontological nursing content,
      curriculum content, and gerontological clinical experiences required. 3. The
      study indicated the following: students were not introduced to a consistent
      philosophy of health for the older client in either the academic or clinical
      setting; 5% of the faculty had a master's or doctorate with a focus in
      gerontology; 2.5% of the students chose a gerontological nursing practicum in
      their last year; 69% of the 49 listed topics were taught in an integrated manner;
      and 7.4% of the clinical hours had a gerontological focus. 4. The experts
      recommended the following: 53% of the topics be integrated and that 47% of the
      topics be taught in a specific course; patient care problems and techniques
      receive more emphasis in the clinical area; 21% of the clinical hours concentrate
      on gerontological nursing; and clinical experiences occur in a variety of health
      care settings to illustrate the elderly's coping abilities to achieve a sense of
      well-being.

PMID- 8301029
TI  - The cellular origin of extracellular matrix constituents.

PMID- 8301031
TI  - Biliary retention in a chronic choledocho-venous fistula in the rat: induction of
      portal hypertension but not of biliary cirrhosis.
AB  - In this study we investigated whether the retention of compounds which are
      excreted into the bile could contribute to portal hypertension in secondary
      biliary cirrhosis. Choledochovenous fistulas were grown in rats for 4 weeks. 6/13
      of the animals had biochemical evidence of partial obstruction. Microsomal
      function, as measured by the aminopyrine breath test, was decreased in all
      animals with biliary retention while microsomal cytochrome P-450 content was
      decreased only in rats with evidence of obstruction. All animals with biliary
      retention with or without partial obstruction had portal hypertension. Animals
      with biliary retention and partial obstruction had hypercholeresis but decreased
      bile salt excretion. All animals with a chronic catheter in the biliary tree had
      a loss of the negative permselectivity of the sinusoidal-canalicular barrier and
      decreased maximal bile secretory pressure. Only animals with biochemical evidence
      of obstruction had moderate fibrosis and ductular proliferation as determined by
      stereological techniques. Unexpectedly, morphometric analysis also revealed an
      increase in hepatocyte mass induced by biliary retention. We conclude that bile
      contains a compound(s) which induces portal hypertension. This putative substance
      is neither bilirubin nor a bile acid since portal hypertension was also observed
      in animals with biliary retention without obstructive signs.

PMID- 8301030
TI  - The effect of antioxidant supplementation on a serum marker of free radical
      activity and abnormal serum biochemistry in alcoholic patients admitted for
      detoxification.
AB  - Alcoholics admitted for detoxification were entered into a double blind placebo
      controlled trial of oral supplementation with an antioxidant cocktail (vitamin E,
      beta carotene, vitamin C and selenium) in order to determine the effect of this
      supplementation on the rate of resolution of a serum marker of free radical
      activity and abnormal serum biochemistry. The molar proportion of linoleic acid
      that was diene conjugated (a marker of free radical activity), was increased in
      the alcoholics 2.9% +/- 1.2 (mean +/- S.D.) compared to normal controls 1.3% +/-
      0.6 (P < 0.0001) but fell at a similar rate during the first week of
      hospitalisation in supplemented and placebo-treated patients with a mean fall of
      53.7% (+/- 16.4 S.D.) in the placebo group and 56.0% (+/- 23.7) (P = 0.32, NS) in
      the antioxidant supplemented group. Similarly, there was no difference in the
      rate of fall between serum aspartate transaminase (AST) concentration in the two
      groups: the placebo group falling by a mean of 68.9% (+/- 35.2) and the
      antioxidant supplemented group falling by 70.1% (+/- 10.0) (P = 0.41, NS) over
      the first 7 days of hospitalization. Alcoholics had low serum concentrations of
      vitamin E compared with controls (15.6 mg/l +/- 6.2 S.D.) which rose more in the
      supplemented group over the period of a week (7.7 mg/l +/- 4.4 to 21.6 mg/l +/-
      5.1) (a mean rise of 180.5%) compared with the placebo group (8.6 mg/l +/- 6.8 to
      9.6 mg/l +/- 5.7)--a mean rise of 11.6% (P = 0.006).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8301032
TI  - Synergism between hepatocytes and Kupffer cells in the activation of fat storing
      cells (perisinusoidal lipocytes).
AB  - This study concerns the cooperation of hepatocytes (PC) and Kupffer cells (KC) in
      the activation of rat liver fat storing cells (FSC) in culture. Various dilutions
      of conditioned media collected from early, serum-free cultures of both cell types
      were added separately and in combination, either simultaneously or sequentially,
      to early, non-confluent, primary cultures of FSC maintained under serum-reduced
      (0.5% fetal calf serum) conditions to determine the effects on proliferation
      (incorporations of [3H]thymidine and bromodeoxyuridine [BrdUrd], DNA-content,
      cell number), transformation and morphology (phase contrast microscopy,
      immunostainings of desmin and smooth muscle-alpha-actin), on the deposition of
      fibronectin and laminin and on the formation of 35S sulfated medium
      proteoglycans. Media of both cell types stimulated cell proliferation in a dose
      dependent manner but combined PC- and KC-conditioned media was most potent and
      increased the incorporation of [3H]thymidine to 4-times above control values. The
      multiplication stimulatory effects visualized by labeling cell nuclei with BrdUrd
      and the increase of cell number per culture well were additive. The sequential
      addition of KC-conditioned medium to FSC preexposed to PC-conditioned medium
      increased the multiplication of FSC further and in an additive manner. The
      mitogenic activity of the PC-medium and the enhancing effect of KC-induced FSC
      proliferation was measured also when PC were damaged by incubation under anoxic
      conditions during generation of the conditioned medium. This observation
      indicates the release of the mitogen by membrane damage presumably from a
      cytoplasmic pool. The PC-medium did not induce either significant morphological
      changes or transformation of FSC towards myofibroblast-like cells. KC, however,
      generated transformation of FSC as indicated by more elongated cells with spindle
      like cellular extensions and a reduction of retinoid droplets. Both these
      morphological effects were visible when PC and KC media were added
      simultaneously. Both media act synergistically on the deposition of fibronectin
      and laminin in FSC cultures and these components were found to be elevated 2.3
      and 2.8-fold, respectively, if the cells were exposed to the combined media.
      Proteoglycan synthesis was also maximally enhanced if FSC were exposed to PC- and
      KC-media simultaneously. These findings suggest the involvement of (damaged)
      hepatocytes in the process of FSC activation. A model of sequential, spatial and
      time-dependent activation of FSC is suggested where cells in the immediate
      proximity of hepatocytes are primed to proliferate by a mitogenic signal released
      by membrane damage presumably from a cytoplasmic pool of injured hepatocytes into
      the pericellular environment. This non-inflammatory stimulation is followed by
      secretions of activated Kupffer cells and other inflammatory cell types which
      further enhance the activation of FSC.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8301033
TI  - Assessment of lidocaine metabolite formation in comparison with other
      quantitative liver function tests.
AB  - In clinical practice, the seriousness of liver disease is assessed based on the
      combined information from clinical examination, routine biochemical tests, and
      liver histology. Recently, the assessment of hepatic lidocaine metabolism has
      been proposed as a quantitative liver function test offering valuable additional
      information. To evaluate whether this new liver function test reflects the
      combined clinical assessment, we prospectively measured lidocaine metabolism in
      111 patients with well characterized liver disease. In addition, lidocaine test
      results were compared with the aminopyrine breath test and the galactose
      elimination capacity. Lidocaine (1 mg/kg) was injected i.v. and serum
      concentrations of its main metabolite monoethylglycinexylidide were determined
      after 15 min. The results varied widely and the means (+/- S.D.) were similar
      among patients with mild liver disease (46 +/- 23 ng/ml), but significantly (P <
      0.05) lower among patients with Child class A cirrhosis (19 +/- 11 ng/ml) or
      Child class B or C cirrhosis (21 +/- 19 ng/ml). The [13C]aminopyrine breath test,
      however, gave a better discrimination among patients with increasing severity of
      liver disease than lidocaine metabolite formation. The galactose elimination
      capacity finally best separated patients with mild liver disease from those with
      cirrhosis. The correlations between any two of the different quantitative liver
      function tests were weak (R2 consistently < 0.2). We conclude that lidocaine
      metabolite formation, like other quantitative liver function tests that are based
      on the microsomal metabolism of model compounds, quantitates a very particular
      enzymatic reaction which may not be representative for the functional reserve of
      the entire organ.

PMID- 8301034
TI  - Measuring lidocaine metabolite--monoethylglycinexylidide as a quantitative index
      of hepatic function in adults with chronic hepatitis and cirrhosis.
AB  - Lidocaine is metabolized to form monoethylglycinexylidide (MEGX) via oxidative N
      deethylation in the liver. To assess the clinical value of this lidocaine
      metabolite as a quantitative liver function test, we measured the serum MEGX
      concentration 15 min after intravenous administration of a single dose of
      lidocaine (1 mg/kg) in 24 adults with chronic hepatitis, 47 patients with
      cirrhosis and 26 normal controls. A fluorescence polarization immunoassay was
      used to obtain the MEGX value. The MEGX concentration in controls was 67 (54-95)
      ng/ml (median with 16th-84th percentile in parentheses), which was higher than 43
      (23-61) ng/ml in patients with chronic hepatitis and 24 (7-52) ng/ml in those
      with cirrhosis (P < 0.05). In addition, the serum MEGX levels are proportional to
      the galactose elimination capacity, and inversely proportional to Pugh's score,
      the prothrombin time and indocyanine green retention ratio. If a MEGX
      concentration of below 54 ng/ml is taken as an indicator of hepatic dysfunction,
      its diagnostic sensitivity for hepatic disorder is 84.5%, specificity 88.5% and
      accuracy 85.6%. Furthermore, after a 10-month follow-up, patients with MEGX
      formation above 30 ng/ml had a higher survival rate than those with a MEGX
      concentration below this level (P = 0.004). In conclusion, the MEGX formation
      test reflects the severity of hepatic dysfunction quite well, making it valuable
      both in the quantitative evaluation of liver function and in the prognostic
      prediction of adults with liver diseases.

PMID- 8301035
TI  - Diurnal pattern of variceal bleeding in cirrhotic patients.
AB  - The aim of this paper was to assess diurnal periodicity in the time pattern of
      the time of onset of acute gastrointestinal bleeding related to portal
      hypertension manifested by hematemesis or melena in cirrhotic patients over a
      period of 24 h. The study was a prospective evaluation of separate and
      consecutive episodes of bleeding requiring admission to hospital following
      hematemesis or melena in cirrhotic patients with the use of cosinor statistical
      analysis to determine rhythmicity. A total 744 episodes of bleeding were studied
      during separate and consecutive hospital admissions over a 68-month period. The
      time of onset of manifestation of variceal bleeding (n = 608) in both alcoholic
      (n = 279) and non-alcoholic (n = 329) cirrhosis and bleeding from non-variceal
      sources excluding peptic ulcer (n = 136) showed a significant diurnal rhythm (P =
      0.005 and P < 0.05, respectively), with two peaks at 08:00 h and 20:00 h. This
      pattern was not modified by sex, age, severity of liver disease, seasonal
      variations or initial presentation with hematemesis or melena on its own. This is
      the first study showing significant diurnal periodicity in the time of onset of
      bleeding in cirrhotic patients. It is also the first study to show periodicity of
      upper gastrointestinal bleeding from any source. The cause for the observed
      rhythmicity is not apparent but parallel changes in portal pressure and/or
      changes in hemostatic factors could explain this observation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8301036
TI  - Gastric secretion and peptic ulceration in cirrhosis.
AB  - Stomach function and secretions are altered significantly in patients with
      cirrhosis, both with or without portal hypertension. This review covers the
      abnormalities of gastric acid and pepsin secretion, and gastrin release.
      Histological and endoscopic changes, and the impaired cytoprotection associated
      with cirrhosis, are discussed in the context of abnormal gastric secretion. In
      addition, the symptomatology and association of H. pylori, and treatment of
      duodenal ulceration in cirrhosis are discussed. It is clear from this review that
      additional studies are needed to further understand gastric function in cirrhotic
      patients.

PMID- 8301037
TI  - Is spontaneous bacterial peritonitis a complication of hospitalization?

PMID- 8301038
TI  - Comment: functional spectrum of sinusoidal endothelial cells.

PMID- 8301039
TI  - Prognosis and long-term recurrence of spontaneous bacterial peritonitis in
      cirrhosis.

PMID- 8301040
TI  - The effect of interferon alpha and prednisolone on the serum concentrations of
      the aminoterminal domain of procollagen type III(PIIIP) and type IV (7-S
      collagen) in patients with chronic hepatitis B.
AB  - Since interferons are reported to inhibit collagen synthesis in vivo and in
      vitro, they are possible anti-fibrogenic drugs. However, little is known about
      the effect of interferons on connective tissue metabolism in liver disease. To
      investigate the effect, serum concentrations of the aminoterminal domain of
      procollagen type III and type IV (7-S collagen) were measured in 16 patients with
      chronic hepatitis B during alpha interferon treatment. The levels were also
      determined during prednisolone withdrawal treatment to investigate the effect on
      hepatic collagen turnover. In patients with chronic hepatitis B, the serum levels
      of both markers were significantly elevated before any treatment (procollagen
      type III: 1.10 +/- 0.39 U/ml, 7-S collagen: 6.69 +/- 3.71 ng/ml) compared with
      levels in 41 healthy volunteers (pro-collagen type III: 0.53 +/- 0.13 U/ml, P <
      0.001; 7-S collagen: 4.72 +/- 0.57 ng/ml, P < 0.001). Both levels were even more
      elevated during interferon therapy (procollagen type III: 1.36 +/- 0.58 U/ml, P <
      0.05; 7-S collagen: 8.77 +/- 4.68 ng/ml, P < 0.01). On the other hand, serum
      procollagen type III and 7-S collagen levels were both decreased during
      prednisolone treatment (procollagen type III: 0.62 +/- 0.13 U/ml, P < 0.001; 7-S
      collagen: 4.66 +/- 1.69 ng/ml, P < 0.01). These preliminary data suggest that
      interferon alpha enhanced, but prednisolone inhibited the turnover of procollagen
      type III and IV in the liver. Further study is required to interpret this
      observation in relation to anti-fibrotic therapy.

PMID- 8301041
TI  - MEGX test in hepatology: the long-sought ultimate quantitative liver function
      test?

PMID- 8301042
TI  - Fulminant hepatic failure after Lepiota mushroom poisoning.
AB  - We present ten patients who suffered from a cyclopeptide syndrome from two
      different foci, one caused by Lepiota helveola (seven cases) and the other by
      Lepiota brunneoincarnata (three cases). Of the ten victims, five recovered
      completely after the intestinal stage and the other five developed a phase of
      visceral involvement with alterations of liver function. In two patients, hepatic
      function became normal after the 7th day after ingestion. Three patients
      developed fulminant hepatitis and two of these died of adult respiratory distress
      syndrome. The fulminant hepatitis patient who later improved developed active
      chronic hepatitis 1 year later. Finally, five patients developed mixed
      polyneuropathy. In this paper the indications for orthotopic liver transplant
      (OLTx) are discussed and the development of late complications such as active
      chronic hepatitis and mixed polyneuropathy are considered.

PMID- 8301043
TI  - Autoantibodies against the human asialoglycoprotein receptor: effects of therapy
      in autoimmune and virus-induced chronic active hepatitis.
AB  - The hepatic asialoglycoprotein receptor (ASGPR) was recently identified as a
      target antigen for both humoral and cellular immune response in inflammatory
      liver diseases. Thereby anti-ASGPR autoantibodies directed against human
      substrate were closely associated with autoimmune chronic active hepatitis. The
      present study compares the occurrence, titer and immunoglobulin classification of
      anti-human(h-)-ASGPR antibodies in 23 patients with newly diagnosed autoimmune
      chronic hepatitis before and after initiation of immunosuppressive therapy to 22
      patients with autoimmune hepatitis in remission. Additionally, 1-year follow-up
      examinations of 42 patients with HBsAg-positive chronic hepatitis and of 32
      patients with chronic hepatitis C receiving recombinant interferon-alpha were
      included. Nineteen of 23 patients with newly diagnosed and 9/22 with autoimmune
      hepatitis in remission, 5/42 with untreated chronic hepatitis B and 5/32 patients
      with chronic hepatitis C exhibited anti-h-ASGPR at the beginning of the study. In
      autoimmune hepatitis anti-h-ASGPR were found in higher titers (median > 1:1000)
      than in viral hepatitis (maximum 1:400). After initiation of immunosuppressive
      therapy in autoimmune hepatitis anti-h-ASGPR decreased sharply. Eight of 19
      patients eliminated anti-h-ASGPR within 18 months in contrast to 11 patients with
      persistent anti-h-ASGPR titer over 18 months and longer. Anti-h-ASGPR with
      maximum titer of 1:600 were detected in 5 patients with chronic hepatitis B
      (transiently in 4/5 patients) and in 2 patients with chronic hepatitis C during
      interferon-alpha. Anti-h-ASGPR were from immunoglobulin classes IgG and IgM in
      cases with untreated autoimmune hepatitis and chronic hepatitis B and C
      exhibiting mainly IgG2-subclass in autoimmune and IgG4 in viral
      hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301044
TI  - Decreased hepatic glucose production in rats with carbon tetrachloride-induced
      cirrhosis.
AB  - Energy metabolism was studied in fed and fasted rats with carbon tetrachloride
      (CCl4)-induced cirrhosis. In situ liver perfusion experiments were performed
      under basal conditions (no substrate added to the perfusate) and after
      stimulation with glucagon (2 nM) and L-alanine (20 mM). Under basal conditions,
      oxygen consumption per gram of liver was reduced in cirrhotic rats irrespective
      of the metabolic state. After addition of glucagon/L-alanine to the perfusate,
      oxygen consumption increased significantly in fed and fasted control and
      cirrhotic rats. Under basal conditions, glucose production was reduced by 76% in
      cirrhotic rats, averaging 0.75 +/- 0.19 vs. 0.18 +/- 0.15 mumol.g liver-1.min-1
      in control and cirrhotic livers, respectively (means +/- S.E.M., P < 0.05). After
      addition of glucagon/L-alanine to the perfusate, glucose production increased in
      both groups and was reduced by 65% in fed cirrhotic as compared with fed control
      rats, averaging 3.63 +/- 0.27 vs. 1.27 +/- 0.17 mumol.g liver-1.min-1 in control
      and cirrhotic rats, respectively (P < 0.05). Stimulated glucose production was
      linearly correlated with the fractional aminopyrine elimination rate constant
      (ABT-k), a measure of hepatic function in vivo. After 12 h of fasting, stimulated
      glucose production was decreased by 15% in control and by 65% in fed cirrhotic
      rats compared with the fed state, averaging 3.07 +/- 0.22 vs. 0.33 +/- 0.03
      mumol.g liver-1.min-1 in control and cirrhotic rats, respectively (P < 0.05).
      After 24 h of starvation, glucose production was not significantly different
      between control and cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301045
TI  - Effect of hypothermic storage in liver allograft preservation solutions on
      vasoactivity and prostacyclin synthesis by the rabbit aorta, in vitro.
AB  - Primary graft dysfunction following orthoptic liver transplantation has been
      ascribed to thrombotic and ischemic complications in a high proportion of cases.
      It has been suggested that hypothermic storage of livers in preservation
      solutions elicits damage to the vascular endothelium. Since the endothelium
      controls vasoactivity and hemostasis via release of endothelium derived relaxing
      factor (EDRF) and prostacyclin (PGI2), storage injury to the endothelium may
      predispose the allograft to thrombosis, ischemia and impaired perfusion. In order
      to test this, the effect of long-term hypothermic storage in modified University
      of Wisconsin solution (UW), kidney perfusion solution (KPS) and minimum essential
      medium (MEM) on phenylephrine (PE)-stimulated contraction and acetylcholine (ACh)
      stimulated relaxation, as well as PGI2 release by rabbit aortic rings was
      investigated. Following cold storage for 24, 48 and 72 h, PE and ACh dose
      response curves were unaffected by storage in MEM, UW or KPS. Following
      hypothermic storage for 24 h and 48 h, PGI2 release (stimulated with PE, ACh,
      arachidonate, fluoride, calcium ionophore and phorbol ester) was not
      significantly altered from zero time responses. These results demonstrate that
      hypothermic storage of rabbit aortic rings in both UW and KPS do not influence
      two key endothelial functions (the release of EDRF or PGI2) which in turn
      indicates that endothelial damage associated with reperfusion following
      hypothermic storage is not causally related to alterations in EDRF and PGI2
      release.

PMID- 8301046
TI  - Hepatic amyloidosis in intravenous drug abusers and AIDS patients.
AB  - The clinical and pathological features of four liver biopsies and 12 autopsies
      from 1981-1990 with hepatic amyloidosis were reviewed. All of the patients had a
      history of both intravenous and subcutaneous cocaine and heroin use with chronic
      suppurative skin ulcers. Five patients were proven to have the acquired
      immunodeficiency syndrome at autopsy. Systemic amyloidosis was diagnosed in only
      five out of the 16 patients prior to death. Hepatomegaly was present in 12
      patients. The amyloid protein was AA in 14 and AL in one case. Definitive
      characterization of the amyloid substance was not possible in one case. There was
      no evidence of multiple myeloma or a plasma cell dyscrasia in the one patient
      with AL amyloid. The amyloid distribution in the liver was both parenchymal and
      vascular in 12 cases. Cholestasis, which appeared to occur preterminally, was the
      only histological finding that correlated with the patient's clinical condition.
      The histological pattern of amyloid in the liver could not predict the type of
      amyloid protein that was identified. Amyloidosis should be considered in the
      differential diagnosis of unexplained hepatomegaly in the acquired
      immunodeficiency syndrome with chronic suppurative infections.

PMID- 8301047
TI  - Neutrophil cytoplasmic autoantibodies after liver transplantation in patients
      with primary sclerosing cholangitis.
AB  - The immunopathogenic importance of neutrophil cytoplasmic autoantibodies in
      ulcerative colitis and primary sclerosing cholangitis is unknown. These
      autoantibodies were investigated before and after liver transplantation in 9
      patients with primary sclerosing cholangitis. Sera from 10 patients transplanted
      for metabolic disorders or hemangioma served as controls. Before liver
      transplantation neutrophil cytoplasmic autoantibodies, producing a perinuclear
      pattern by indirect immunofluorescence on ethanol fixed neutrophils, were present
      in all patients with primary sclerosing cholangitis. A decline in titer was noted
      in the first months after liver transplantation. During long-term follow up, the
      autoantibodies remained present and most often the titer did not differ from
      before transplantation. They were not directed against proteinase 3,
      myeloperoxidase, elastase or lactoferrin. All but one of the control patients
      were negative for the autoantibody. No relation was seen, before or after
      transplantation, with ulcerative colitis or proctocolectomy. There was no
      recurrence of primary sclerosing cholangitis in any of the patients as judged by
      liver histology. We conclude that neutrophil cytoplasmic autoantibodies remain
      present after liver transplantation for primary sclerosing cholangitis and that
      its synthesis is not related to the presence of the diseased organ(s). The
      primary disease process in primary sclerosing cholangitis and ulcerative colitis
      may well be a disturbance of the immune system.

PMID- 8301048
TI  - Hepatic hemodynamic features in patients with esophageal or gastric varices.
AB  - One hundred and fifty cirrhotic patients with or without esophageal varices
      and/or gastric varices were investigated by endoscopy and hepatic venous
      catheterization to evaluate differences in the degree of portal hypertension,
      main portal venous diameter and frequency of portal systemic encephalopathy.
      Hemodynamic values were correlated with varices size as assessed by endoscopy.
      Patients with large gastric varices had wedged hepatic venous pressures and
      hepatic venous pressure gradients which were lower than patients with esophageal
      varices only, but similar to patients without varices. In addition, in patients
      with large gastric varices, a decrease in the diameter of the main portal vein
      and an increase in the incidence of chronic portal systemic encephalopathy were
      noted. Our results implied that patients with large gastric varices presented
      different hemodynamic features including the degree of portal hypertension and
      the incidence of portal systemic encephalopathy from patients with esophageal
      varices only.

PMID- 8301049
TI  - Early colchicine administration reduces hepatic fibrosis and portal hypertension
      in rats with bile duct ligation.
AB  - Chronic administration of colchicine has been suggested as a potential treatment
      for hepatic fibrosis. The purpose of this study was to examine the effects of
      chronic oral administration of colchicine on the histological and hemodynamic
      abnormalities of bile duct ligation in the rat. Forty-eight rats with ligation
      section of the common bile duct were randomly and blindly assigned to receive
      either colchicine (50 mu/kg day) or placebo by gavage for 4 weeks. At the end of
      the treatment period, morphometric analysis showed that hepatocyte and sinusoidal
      volume fractions were significantly higher in rats treated with colchicine than
      in rats receiving placebo (42.4 +/- 1.3 vs. 32.1 +/- 2.6% (mean +/- S.E.) and 8.3
      +/- 0.6 vs 4.7 +/- 0.4%, respectively), while bile duct volume fractions
      (reflecting bile ductular proliferation) and connective tissue fractions were
      significantly lower in rats treated with colchicine than in rats receiving
      placebo (12.1 +/- 0.9 vs. 17.0 +/- 0.1% and 37.2 +/- 0.9 vs. 46.1 +/- 2.0%,
      respectively). Portal pressure (13.4 +/- 0.7 vs. 17.8 +/- 0.5 mmHg), portal
      tributary blood flow (5.8 +/- 0.4 vs. 8.7 +/- 0.5 ml.min-1.100 g-1) and cardiac
      index (40.8 +/- 2.3 vs. 50.6 +/- 1.5 ml.min-1.100 g-1) were significantly lower
      in colchicine-treated rats than in placebo treated animals. In conclusion, in
      rats with bile duct ligation, colchicine limits the severity of liver lesions
      and, consequently, of portal hypertension and hyperkinetic syndrome.

PMID- 8301050
TI  - Adaptive changes of hepatic bile salt transport in a model of reversible
      interruption of the enterohepatic circulation in the rat.
AB  - The reversibility and time course of the adaptive changes in hepatic bile salt
      transport related to modifications of the bile salt enterohepatic circulation and
      bile salt pool size have not been previously studied. For this reason a model of
      reversible interruption of entero-hepatic circulation was characterized in
      unrestrained rats, which allowed the study of changes in hepatic bile salt
      transport following bile salt pool depletion and subsequent restoration by either
      the de novo synthesis of bile acids or i.v. administration of exogenous
      taurocholate. Rats subjected to biliary drainage for 24 h through a transduodenal
      common bile duct cannula, followed by removal of the cannula and restoration of
      the enterohepatic circulation were studied at 24, 48 and 72 h. Neither light and
      electron microscopy examination nor plasma biochemical parameters showed evidence
      of necrosis, fibrosis, cholestasis or inflammatory changes. Maximum taurocholate
      secretory rate decreased to 50% following 24-h bile salt depletion. After
      restoration of the enterohepatic circulation maximum taurocholate secretory rate
      progressively increased to normal values at 72 h, following the normalization of
      the bile salt pool size, which had a similar composition compared with controls.
      The same effect was obtained when the native bile salt pool was substituted with
      exogenous taurocholate. Thus, adaptive down-regulation of hepatic bile salt
      transport capacity is a reversible process, related to restoration of entero
      hepatic circulation and normalization of bile salt pool size.

PMID- 8301051
TI  - Failure of combined efforts: propranolol and sclerotherapy do not add up to the
      prevention of variceal bleeding.

PMID- 8301052
TI  - Cirrhosis, renal function and NSAIDs.

PMID- 8301053
TI  - Identification of hepatitis B virus-DNA in the liver by in situ hybridization
      using a biotinylated probe. Relation to HBcAg expression and histology.
AB  - The cellular localisation of hepatitis B virus (HBV)-DNA in liver tissue was
      studied by in situ hybridisation using biotinylated and radiolabelled probes on
      samples from HBsAg carriers with a spectrum of disease and related to the
      presence of HBV-DNA in serum and intrahepatic HBcAg expression. Sixteen of the 31
      patients studied were seropositive for HBV-DNA; nine had chronic active hepatitis
      and seven had chronic persistent hepatitis. HBV-DNA was detected in the liver
      tissue in seven of these patients. In each, HBV-DNA was detected in both
      cytoplasm and nuclei. All seven also had nuclear and/or cytoplasmic HBcAg which
      in six was associated with chronic active hepatitis. HBcAg (without tissue HBV
      DNA) was detected in the remaining nine patients with an exclusively nuclear
      pattern in two. Fifteen patients were seronegative for HBV-DNA. HBV-DNA was not
      detected in the tissue of any of these. Three of these were HBcAg positive but in
      each this was confined to occasional nuclei and each had inactive disease. The
      close association between the presence of detectable HBV-DNA in tissue,
      cytoplasmic HBV-DNA expression and chronic active hepatitis in one group and a
      failure to detect HBV-DNA in those with nuclear HBcAg and benign disease suggests
      that there may be two distinct patterns of HBV replication in chronic HBV
      carriers which may influence the development of liver damage.

PMID- 8301054
TI  - Absence of hepatitis C virus in British patients with type 1 autoimmune chronic
      active hepatitis--a polymerase chain reaction and serological study.
AB  - Despite several studies from continental Europe reporting a high prevalence of
      antibodies to the hepatitis C virus (HCV), there has been little evidence of such
      infection in patients from the United Kingdom. The use of the polymerase chain
      reaction combined with two separate second generation anti-HCV assays is reported
      here in 58 UK patients with well-documented autoimmune chronic active hepatitis.
      All patients were in corticosteroid induced remission. All sera were collected
      prospectively for the specific purpose of this study. HCV-RNA was not detected by
      use of the polymerase chain reaction in any of the patients and antibodies to HCV
      were only detected in one patient. No evidence was found for the involvement of
      the hepatitis C virus in UK patients with classical, corticosteroid sensitive
      autoimmune chronic active hepatitis.

PMID- 8301055
TI  - Interferon-alpha increases prostaglandin E2 production by cultured liver biopsy
      in patients with chronic viral hepatitis: can non-steroidal anti-inflammatory
      drugs improve the therapeutic response to interferon?
AB  - Arachidonic acid metabolites seem to play an important role in modulating the
      post-receptorial activity of interferon-alpha. In this study the effect of
      interferon-alpha on prostaglandin E2 production was evaluated in cultured liver
      tissue in 18 patients with chronic active hepatitis related to viral infection (9
      hepatitis B virus (HBV) and 9 hepatitis C virus (HCV) positive) and in 7
      uninfected patients with various liver diseases. The results show that interferon
      alpha induces a significant increase in prostaglandin E2 production in both HBV
      and HCV chronic active hepatitis. Since the inhibition of the cyclooxygenase
      pathway increases antiviral protein synthesis and prostaglandin E2 has an
      immunosuppressive activity, this finding seems to suggest that a combined therapy
      (interferon-alpha plus non-steroidal anti-inflammatory drugs) should be indicated
      at least for patients who do not respond to interferon therapy alone.

PMID- 8301056
TI  - Clinical applications of ICG Finger Monitor in patients with liver disease.
AB  - The indocyanine green (ICG) Finger Monitor system is a non-invasive indication of
      ICG concentrations in the blood. In this study, significant correlation was found
      between the sensor signal voltage and plasma ICG concentrations ranging from 0.04
      mg/dl to 1.0 mg/dl (r = 0.998, P < 0.001) in vivo. The ICG clearance curve showed
      an initial sharp rise 20-30 s after bolus injection, followed by a small rise.
      The concentration then deceased exponentially. In 196 patients with chronic liver
      disease, there was a close correlation between the KICG (plasma disappearance
      rate) and R15 (blood retention ratio at 15 min) (r = 0.886, P < 0.001, r = 0.912,
      P < 0.001) and corresponding values calculated by the conventional ICG method. In
      263 cases with chronic liver disease, the plasma disappearance rates calculated
      using this monitor (mean +/- S.D.) were 0.156 +/- 0.064 (n = 20) in the control
      group, 0.129 +/- 0.060 (n = 92) in the chronic hepatitis group, 0.048 +/- 0.025
      (n = 59) in the cirrhosis group and 0.059 +/- 0.03, (n = 92) in the group with
      hepatocellular carcinoma. A significant difference in the plasma disappearance
      rate and blood retention ratios 15 min after injection of ICG using this system
      was observed between control cases and the chronic hepatitis and cirrhosis groups
      (P < 0.0001). In 36 cases, the time from injection to the appearance of ICG in
      the fingertip significantly decreased in the cirrhosis group (P < 0.01). The ICG
      Finger Monitor system was shown to be useful clinically as well as for research
      due to its accuracy and non-invasive nature.

PMID- 8301057
TI  - Energy expenditure and substrate metabolism after oral fructose in patients with
      cirrhosis.
AB  - There is little information on the metabolic response to ingested fructose in
      patients with cirrhosis. Glucose kinetics, plasma lipid and blood lactate levels,
      whole body substrate oxidation rates and energy expenditure were measured
      following ingestion of 75 g fructose, in 8 cirrhotic patients and 6 controls.
      Fasting plasma glucose levels and rates of glucose appearance (Ra) and
      disappearance (Rd) were similar. The basal rate of lipolysis was higher in
      cirrhotic patients (P < 0.05), but whole body lipid and carbohydrate oxidation
      rates and energy expenditure were similar. After fructose ingestion, plasma
      fructose levels were much higher in cirrhotic patients (P < 0.001) and the
      incremental area under the plasma glucose curve was twice that of controls (P <
      0.05). The increase in glucose in patients with cirrhosis was due to an increase
      in glucose Ra and an initial reduction in glucose Rd. Plasma non-esterified fatty
      acid levels fell to similar low levels in both groups. Glycerol levels fell in
      controls (P < 0.05) but not in cirrhotic patients. Blood lactate levels, fasting
      and after oral fructose, were similar in cirrhotics and controls. The time course
      of suppression of lipid oxidation and stimulation of carbohydrate oxidation was
      more closely related to fructose levels than to serum fatty acid levels in both
      groups. The percent suppression and total quantity of lipid oxidized in 4 h after
      fructose were not significantly different, but the suppressed lipid oxidation
      rates and elevated carbohydrate oxidation rates were sustained for longer in the
      cirrhotics. The data suggest that fructose uptake and metabolism inhibits
      oxidation of intracellular lipid. There was a smaller increase in energy
      expenditure after fructose in cirrhotics (P < 0.001), but normal overall storage
      of fructose; the likely explanation is reduced first pass hepatic fructose uptake
      in cirrhotics making more fructose available to the periphery for incorporation
      into muscle glycogen. The energy cost of storing fructose as muscle glycogen is
      less than that of storing it as liver glycogen. Preferential incorporation of
      fructose carbon into muscle glycogen, with lower rates of hepatic glycogen and
      triglyceride synthesis, would therefore result in less energy expenditure after a
      fructose load in cirrhotics.

PMID- 8301058
TI  - Presence of HIV-1 in human parenchymal and non-parenchymal liver cells in vivo.
AB  - The infection of liver cells by HIV-1 was investigated in vivo. Liver biopsies
      from 13 anti-HIV-1 antibody-positive patients were studied and HIV-1 DNA was
      revealed by polymerase chain reaction (PCR) in eight. In situ hybridization
      demonstrated the presence of HIV-1 RNA in all eight PCR-positive liver specimens.
      Mononuclear inflammatory cells in the portal tracts and Kupffer cells were
      labeled by a HIV-1 35S-RNA probe in all cases and by an anti-p24 monoclonal
      antibody, in seven cases. In addition, hepatocytes also clearly scored positive
      for HIV-1 RNA in three cases. These results demonstrate the infection of both
      parenchymal and non-parenchymal liver cells by HIV-1 in vivo and therefore show
      that HIV-1 can infect an epithelial CD4-negative cell type.

PMID- 8301059
TI  - Pilot study of natural human interleukin-2 in patients with chronic hepatitis B.
      Immunomodulatory and antiviral effects.
AB  - Ten patients with chronic hepatitis B received increasing doses of nIL-2 (30,000
      U, 100,000 U, 300,000 U, 1.0 million U) subcutaneously in a phase I trial. Each
      dose was applied once per week over 3 weeks. Serum samples were taken before and
      2, 12, 24, 48 and 72 h after the first application of each dose level. Serum
      concentrations of interleukin-1 (IL-1), IL-2, IL-6, interferon-alfa (IFN-alpha),
      IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and GM-CSF as well as the
      cytokine-dependent serum components neopterin, beta-2-microglobulin (B2M), C
      reactive protein (CPR), soluble IL-2-receptor (sIL-2R) and 2'-5'-oligoadenylate
      synthetase (2-5 OA) were assayed using ELISAs and RIAs. None of the samples
      tested contained measurable cytokine levels other than IL-2. A low and non-toxic
      dose of 300,000 U nIL-2 was already biologically active with induction of
      neopterin, B2M and sIL-2R. Dose-dependent changes peaked 24-48 h after
      application. The same patients were then enrolled in a phase II trial. Treatment
      in five of the patients was continued twice per week for 3 months with a
      biologically active dose of 300,000 U nIL-2 subcutaneously. Two of these patients
      as well as another five patients from the original group were treated with 1.0
      million U nIL-2 subcutaneously, twice weekly for 3 months. Neither a biologically
      active but non-toxic dose of 300,000 U nIL-2, nor a toxic dose of 1.0 million U
      resulted in permanent clearance of hepatitis B early antigen (HBeAg).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301060
TI  - Endoscopic ultrasonography classification of gastric varices in patients with
      cirrhosis. Comparison with endoscopic findings.
AB  - Endoscopic ultrasonography was performed in 80 cirrhotic patients and 50 control
      subjects. The aim of the study was to describe and classify the vascular
      abnormalities of the gastric wall as observed on echoendoscopy in cirrhotic
      patients and to compare the data with endoscopy. The size of gastric varices was
      classified into 3 grades: grade 0 (none), grade 1 (small or non-confluent varices
      < 5 mm), grade 2 (large or confluent varices > or = 5 mm). The abnormalities of
      the gastric wall were classified into 3 grades: 0 (none), grade 1 (thickening and
      brilliance of the third hyperechogenic layer with or without fine internal
      anechogenic structures), grade 2 (visible vessels in the third layer which deform
      the entire wall, with penetrating varices). Endoscopy provides better
      visualization of esophageal varices than echoendoscopy but does not detect
      gastric varices and the first signs of portal hypertension as well. In conclusion
      echoendoscopy should be a routine examination for screening portal hypertension
      in cirrhotic patients and could be used in therapeutic follow-up.

PMID- 8301061
TI  - Inflammatory pseudotumour of the liver: antecedent causes and clinical
      experience.
AB  - We present a case in which inflammatory pseudotumour of the liver which appears
      to complicate Caroli's disease. We have reviewed the literature in hepatic
      inflammatory pseudotumour with particular emphasis on underlying causes. We were
      able to find 45 reported cases, with adequate clinical data in 42; in these only
      7 showed a probable antecedent cause. There were gallstones in another 5, giving
      a prevalence not significantly different to that within the general population.
      Hepatic inflammatory pseudotumour typically presents with a history of fever,
      anorexia, loss of weight, hepatic pain, jaundice and a detectable liver mass (or
      masses). The diagnosis of inflammatory pseudotumour should be particularly
      considered when there is a history of previous inflammatory hepato-biliary
      disease. Preoperative or intra-operative diagnosis might then avoid major hepatic
      surgery.

PMID- 8301062
TI  - Effects of imidazole-salicylate on renal function and the diuretic action of
      furosemide in cirrhotic patients with ascites.
AB  - Imidazole-salicylate is a non-steroidal anti-inflammatory drug with limited
      inhibitory effects on prostaglandin synthesis. The renal effects of this drug
      were investigated by a double-blind cross-over study in 10 patients with
      cirrhosis and ascites. Two therapeutic doses of imidazole-salicylate (750 mg
      each) were given at midnight and 08:00 h and 80 mg of furosemide were injected
      intravenously at 09:00 h. The same procedure was followed on another day but a
      placebo replaced imidazole-salicylate. Renal function (creatinine clearance, free
      water and electrolyte excretions) and urinary excretion of prostaglandin E, 6
      keto-prostaglandin F1 alpha and thromboxane B2 were evaluated for 8 h after the
      first dose of the drug and for 2 h after furosemide injection. Platelet
      thromboxane production was also determined 9 h after the first administration of
      drug or placebo. Imidazole-salicylate did not affect renal function or inhibit
      kidney prostanoid production either under basal conditions or after the
      stimulating effect of furosemide. On the contrary, imidazole-salicylate
      significantly inhibited platelet thromboxane production (45.8 +/- 9 vs. 69.4 +/-
      7.5 ng/ml, P < 0.05). These results suggest that imidazole-salicylate is an anti
      inflammatory drug that can be given to patients with decompensated cirrhosis
      without risk of inhibiting kidney prostaglandin synthesis or the renal response
      to furosemide.

PMID- 8301063
TI  - Elevated circulating plasma endothelin-1 concentrations in cirrhosis.
AB  - As endothelin-1 (ET-1), a potent vasoconstricting peptide, may play a role in the
      circulatory derangement and renal impairment in cirrhosis, the aim of the present
      study was to investigate plasma concentrations of ET-1 in different vascular beds
      in relation to clinical and biochemical parameters of liver function. Median
      brachial venous ET-1 concentrations were substantially higher in patients with
      cirrhosis (3.40 pg/ml, range: 1.25-7.84, n = 24) than in controls (1.53 pg/ml,
      range: 0.78-2.12, n = 11) (P < 0.00005). In patients with cirrhosis ET-1 was
      directly correlated to serum creatinine (r = 0.70, P < 0.0001) and aspartate
      aminotransferase (r = 0.44, P < 0.03) and negatively correlated to serum sodium
      (r = -0.58, P < 0.003). In patients who underwent liver vein catheterization (n =
      8), no significant differences were found in ET-1 plasma concentration between
      the liver, renal, or femoral veins on the one hand and the femoral artery on the
      other (P > 0.1), indicating no major net elimination or release in the liver,
      kidney or lower limb. A significant negative correlation was found between
      systolic and diastolic blood pressures on the one hand and circulating ET-1 on
      the other (r = -0.71, P < 0.05). In conclusion, circulating ET-1 is elevated in
      cirrhosis and related to markers of systemic circulation and renal function, thus
      suggesting a role for ET-1 in the circulatory derangement and nephropathy in
      cirrhosis. Locations of major net elimination or release of ET-1 were not
      identified.

PMID- 8301064
TI  - A prospective randomized study to evaluate propranolol in patients undergoing
      long-term endoscopic sclerotherapy.
AB  - A prospective randomized double-blind study was conducted to evaluate the
      efficacy of propranolol in patients with portal hypertension undergoing long-term
      endoscopic sclerotherapy (EST) for recurrent variceal bleeding. Consecutive
      patients with portal hypertension (Child's class A or B) due to cirrhosis (n =
      72), non-cirrhotic portal fibrosis (n = 29) and extrahepatic portal venous
      obstruction (n = 13) attending the liver clinic of a tertiary care center were
      included in the study. All patients had had at least one documented episode of
      variceal bleed in the previous 4 weeks. Fifty-eight patients received propranolol
      and 56 received placebo in addition to weekly EST. Rebleeding occurred in 12
      (21%) patients in the placebo group and 10 (17%) patients in the propranolol
      group during a mean follow-up period of 24.4 +/- 10.4 months in the former and
      23.8 +/- 9.2 months in the latter group (P > 0.1). The number of episodes of
      rebleeding (14 in the placebo and 12 in the propranolol group) were also similar
      (P > 0.1). The median bleeding-free period was more than 40 months in both
      treatment groups (P > 0.1). The mean transfusion requirements and the number of
      hospital admissions for rebleeding were also similar in the two treatment groups
      (P > 0.1). Complete obliteration of varices was achieved in 44 (78.9%) patients
      in the placebo group and 43 (75.5%) patients in the propranolol group (P > 0.1).
      Recurrence of new varices was seen in two patients in the placebo and in three of
      those in the propranolol group. Seven patients in the placebo group and five in
      the propranolol group died (P > 0.1). Complications related to EST were similar
      in the two treatment groups but additional adverse effects were observed in the
      propranolol group. The cumulative incidence of rebleeding in the placebo group
      was 12.7 and in the propranolol group it was 11.2 per 100 patient years of follow
      up. It is concluded that the addition of propranolol in patients with portal
      hypertension and fair hepatic function on long-term EST does not confer any
      additional benefit.

PMID- 8301065
TI  - Propranolol in the prevention of recurrent upper gastrointestinal bleeding in
      patients with cirrhosis undergoing endoscopic sclerotherapy. A randomized
      controlled trial.
AB  - The purpose of this study was to investigate the possible value of continuous
      administration of propranolol in the prevention of recurrent upper
      gastrointestinal bleeding in patients with cirrhosis undergoing chronic
      endoscopic sclerotherapy. Among 239 patients admitted for acute variceal
      bleeding, 85 with cirrhosis were randomized to receive sclerotherapy either alone
      (40) or in combination with propranolol (45). Sclerotherapy was carried out with
      an intravariceal injection of 5% ethanolamine oleate through a fiberoptic
      endoscope. The procedure was performed every week, until the esophageal varices
      at the gastroesophageal junction were too small for any further injections.
      Varices were reinjected if they recurred. Propranolol was given orally twice a
      day until heart rate was reduced by 25% in the resting position. The mean follow
      up period was 23.2 and 24.2 months for sclerotherapy and the sclerotherapy plus
      propranolol groups, respectively. During this period a significant (P = 0.001)
      reduction in the recurrence of esophageal varices was observed in patients
      treated with the combination of sclerotherapy plus propranolol compared with
      those treated with sclerotherapy alone. However, the time of rebleeding from any
      source or from esophageal varices did not differ significantly between the two
      groups. In the sclerotherapy group 21 patients rebled (35 bleeding episodes)
      compared with 14 (22 episodes) in the combination therapy group. Patients in the
      sclerotherapy group were more prone to bleed from gastric varices and congestive
      gastropathy than patients treated with the combination of sclerotherapy plus
      propranolol (P = 0.012). Twenty-five patients in the endoscopic sclerotherapy
      group developed complications attributed to sclerotherapy compared with 23
      patients in the sclerotherapy plus propranolol group. Complications directly
      attributable to propranolol were observed in 11 patients. Three of these patients
      stopped taking the drug due to heart failure (1) and flapping tremor (2). Eight
      patients (17.8%) died in the latter group while the corresponding figure in the
      sclerotherapy group was nine (22.5%). It is concluded that the continuous
      administration of propranolol may reduce incidences of recurrent upper
      gastrointestinal hemorrhage from gastric sources in patients with cirrhosis
      undergoing chronic sclerotherapy.

PMID- 8301066
TI  - Point mutations of the P53 gene, human hepatocellular carcinoma and aflatoxins.
AB  - The tumor suppressor p53 exerts important protective functions towards DNA
      damaging agents. Its inactivation by allelic deletions or point mutations within
      the P53 gene as well as complex formation of wildtype p53 with cellular or viral
      proteins is a common and crucial event in carcinogenesis. Mutations increase the
      half-life of the p53 protein allowing the immunohistochemical detection and anti
      p53 antibody formation. Distinct G to T point mutations in codon 249 leading to a
      substitution of the basic amino acid arginine by the neutral amino acid serine
      are responsible for the altered functionality of the mutant gene product and were
      originally identified in 8 of 16 Chinese and 5 of 10 African HCC patients. Both
      groups are frequently exposed to mycotoxin contaminations of their food. Today an
      average P53 gene mutation rate of 25% is assumed for high-aflatoxin B1-exposure
      regions. This is double the rate observed in low-aflatoxin B1-exposure countries.
      Although many HCC patients displaying P53 mutations also suffer from HBV
      infection, which itself can lead to rearrangements of P53 coding regions or
      induce the synthesis of viral proteins possibly interacting with p53, the
      specific G to T transversion within codon 249 of the P53 gene seems to directly
      reflect the extent of aflatoxin B1 exposure.

PMID- 8301067
TI  - Nitric oxide in alcohol-induced liver failure.

PMID- 8301068
TI  - Transverse myelitis following hepatitis B vaccination.

PMID- 8301069
TI  - Ribavirin therapy in chronic delta hepatitis.

PMID- 8301070
TI  - Hepatitis B virus (HBV) genome in antibody positive hepatocellular carcinoma
      (HCC)

PMID- 8301071
TI  - Infection of peripheral blood mononuclear cells by hepatitis C virus.

PMID- 8301072
TI  - Efficacy of low-dose captopril in addition to furosemide and spironolactone in
      patients with decompensated liver disease during blunted diuresis.

PMID- 8301073
TI  - Introduction: "It's only a word".

PMID- 8301074
TI  - Silenced resistances and conflictual identities: lesbians in France, 1930-1968.
AB  - Between the publication of Colette's Le pur et l'impur in 1932 and the emergence
      of lesbian groups in 1970-1971, silence and invisibility seem to have set in a
      society which remained traditional as far as gender roles and heterosexual norms
      were concerned. Through studying a few literary works and tapping the lesbian
      memory by the methods of oral history, however, it is possible to trace some
      aspects of the lesbian existence during this period and especially to document
      the key issues of self-definition and resistance in front of the dominant
      categorizations, stigmatisation and repression. A strong sense of individual
      legitimacy and claim to happiness stand in sharp contrast to the weakness of
      collective subcultural constructions; this appears in the ambivalence-as for
      every minority identity-towards the identification as a group and the word
      "lesbian" itself. This, being the background of the lesbian movement after 1970,
      may help one to understand some of its characteristics.

PMID- 8301075
TI  - Twentieth century lesbians: should we revive memory or break with the past.
AB  - It is possible, through a reconsideration of historical facts, which have been
      relegated to the category of legends or myths, and widely scattered, to rethink
      the conditions in which some societies have conceived of possible sexual
      permutations. Amazons created, on the one hand, an autonomous and original social
      model which was exclusively homosexual. And on the other, a group of cities in
      Ionia, in the islands or cities other than Athens, provided social patterns for
      differing sexual practices. De-centering the scholar's vision in terms of
      Athenian thought and politics, while referring to all contemporary homosexual
      concepts and behaviours, allows a largely neglected past to emerge today.

PMID- 8301076
TI  - Paederasty and political life in archaic Greek cities.
AB  - This article deals with the importance of paederasty in political life of Archaic
      Greece. It shows that paederasty was present since the beginning of Greek
      history, in many cities, and at the highest levels of society. This study allows
      one to say that paederasty is not an "historical accident," late in history and
      geographically localisable, but is part of the self-definition of Greece since
      its remotest past.

PMID- 8301077
TI  - Homosexual exile: the textuality of the imaginary paradise, 1800-1980.

PMID- 8301078
TI  - On the esthetics of pleasures: guidelines for a socio-anthropology of
      (homo)sexualities.
AB  - The goal of this article is to contribute to the elaboration of a socio
      anthropology of the sexualities in an epistemological perspective by setting
      forward some theoretical guidelines I have been adopting in my present research
      project. I propose the notion of "culture of sexualities" like a system that
      focuses on the socio-cultural and historical construction of sexualities in
      relation with the global culture's internal logic in each given society. It
      includes biological sex, social sex, gender problematics, sexual identities,
      sexual roles, sexual orientations, and social stereotypes in its inter-relations
      and in connection with social and historical changing. I also give attention to
      the relations between the "sexual" and the "non sexual" sociabilities
      ("homosocial" or "heterosocial") and to the importance of sexualities' social
      imaginary in the elaboration of a relativist and constructivist approach.

PMID- 8301079
TI  - A homosexual militant at the beginning of the century: Marc Andre Raffalovich.
AB  - This work is based on my thesis from Aix en Provence on French Civilisation and
      Letters (1984). The head of the examinations was the writer Raymond Jean. My idea
      is to show how the decadent writer and poet Marc Andre Raffalovich fought against
      the personalities in science concerning homosexuality with a new point of view
      and with great difficulty, shedding new light on this subject in a review from
      1886 to 1914 under the direction of Dr. Alexandre Lacassagne Les Archives
      d'Anthropologie Criminelle de Medecine Legale et de Psychologie Normale et
      Pathologique published in 1886, edited by the director A. Lacassagne, professor
      and chairman of legal medicine, Lyon, and author of the article "Pederastie,"
      Dictionnaire Encyclopedique des Sciences Medicales, volume XXII published in
      1886. In 1893, he wrote an introduction for l'Inversion Sexuelle of Dr. Julien
      Chevalier (Paris: Masson-Lyon Storck). This monthly review "d'au moins 80 pages"
      was called L'Ecole Lyonnaise, and so to say, l'Ecole Francaise d'Anthropologie
      Criminelle, which defends against l'Ecole Italienne of Lombroso, the culturalist
      theory of the birth of the criminal; according to this ecole du milieu social:
      "La Societe a les criminels qu'elle merite" (The society has criminals it
      deserves). After the first world war, it was to be overridden by the Marxist
      analysis.

PMID- 8301080
TI  - The minitel: the glittering future of a new invention.
AB  - In the eighties a new medium has found its way in French society: the minitel. It
      has influenced gay communication immediately, heavily and constantly. The role of
      the minitel in the gay world of the eighties is gone into. Some ideas are put
      forward as to why the minitel has been so successful in France. A connection is
      made between the minitel's success and the role of anonymity and promiscuity in
      the gay world. A theoretical explanation is sought in the link between
      urbanisation and social communication.

PMID- 8301081
TI  - Gai Pied after ten years: a commercial success, a moral bankruptcy?
AB  - In this article, Jan Willem Duyvendak and Mattias Duyves describe and analyze the
      development of France's most important gay magazine: Gai Pied. They discuss the
      development of this weekly publication in relation to changes that have taken
      place in the French homosexual movement and the broader political context in the
      intervening years. Gai Pied was the most successful innovation of the gay
      movement in France at the end of the seventies. Indeed, in contemporary France
      the gay press seems to be the only substantial organized gay "movement" outside
      the AIDS network. Duyvendak and Duyves ask the question whether the price Gai
      Pied has paid for becoming so centralized and dominant (more commercialized and
      less challenging to the readers) has been too high.

PMID- 8301082
TI  - Identification or the pluralisation of the person.
AB  - Man's life cannot be condensed into a single function, one ideology or a single
      sex. This is what one may see in our contemporary reality which becomes more and
      more heterogeneous in so many areas such as sex, speech, and work. The role of
      the double, the guardian angel, the anthropological twin, is at present held by a
      sort of psychological and social duplicity which plays with the various
      assignments attributed to identity. If one considers the shadow as a metaphor of
      the double, of plurality, one is led on one hand to a more complex order and on
      the other hand, to a communal conception of life. Since everything has its place
      in social reality, everyone can live there. The essential lesson of openness,
      induced through the notion of 'person', is not to deny what may seem strange or
      foreign, not to satisfy oneself with tolerance, but to appreciate the solid
      organicity it serves to impulse at its just value.

PMID- 8301083
TI  - Foucault: the imaginary sex.
AB  - Foucault has haphazardly written many things about contemporary homosexuality (we
      have only two short interesting interviews on the subject). But La Volonte de
      Savoir develops a new idea about the modern sexuality inclination; Surveiller et
      Punir is a real political economy of the human body; and Foucault's last two
      books on antiquity give us a new point of view as regards the relations of
      subject to desire. This combined analysis constitutes a coherent structure of
      proposals that helps to enlighten crucial matters relevant to the gay community,
      particularly when it deals with what sexual "freedom and sexual identity mean.
      The answers outlined by Foucault yield two questions and two meanings as regards
      homosexuality nowadays, which cannot be kept apart from experience, and without
      any need of theoretical dissociation, if we are to understand the problem better.

PMID- 8301084
TI  - Between man and woman: the character of the lesbian.
AB  - Homosexuality, or inversion, is defined by medical discourses since the middle of
      the XIXth century, as a condition which radically marks individuals so labelled.
      Through those discourses, a figure, a character, is built. It is no longer
      precise sexual acts which are at stake, but the totality of the person, who has
      salient features, biological, psychological as well as behavioral. Those salient
      features are built on gender mixing, even on sexual characteristics mixing. The
      inverts, in such a definition, stress the bipolarity of sexes because they embody
      an intermediate state, the 'third sex'. But this conceptualisation implies also a
      reinforcement of the two poles of categorisation. Homosexuals do not follow 'the
      natural law' which defines men and women. Third part excluded from
      bicategorisation, indifferentiate freaks, those characters are analysers for
      social definitions of sexes, genders and their evolution.

PMID- 8301085
TI  - Myths and historiographies of lesbian sexuality.
AB  - In this paper I address the issue of female sexuality, in search of historical
      situations of female pleasure and enjoyment. I will thereby (re)unite or confuse
      lesbian and heterosexual identities in order to explore a method of historical
      research on lesbian sexuality. "Lesbian identity," as we know it today, is a
      sociocultural construction of the western world, thus this confusion seems
      necessary. The application of this or any notion of "lesbian identity" to
      historical and cultural periods prior to or outside of twentieth century western
      culture, would thus keep many moments, encounters and sensibilities, in which
      lesbian sexuality plays its part, out of our sight.

PMID- 8301086
TI  - Sappho mythified, Sappho mystified or the metamorphoses of Sappho in fin de
      siecle France.
AB  - This article is concerned with the way the mythical figure of Sappho was
      constructed by writers and painters at the end of the 19th century. At the turn
      of the century Sappho's work was translated anew, while Sappho herself was turned
      into a personnage romanesque. She then became the object of various
      "metamorphoses" best conceived in terms of an infinite reproduction of the
      poetess under different guises-she is given new faces, new destinies and even new
      names-that nevertheless affect a singular "metamorphosis"; Sappho is sexualized,
      transformed from the poetess into a lesbian, symbol of all that is contre-nature
      and thus the original aberrant woman (e.g., "viragos," bluestockings, feminists
      and later garconnes) as it was then being constructed by literary and medical
      discourse. But if no longer an untouchable myth, this actualized Sappho can be
      considered as a keyfigure to the understanding of fin de siecle fantasies and
      fears about lesbianism and female sexuality in general.

PMID- 8301087
TI  - French Renaissance travel accounts: images of sin, visions of the New World.
AB  - Accounts of French Renaissance travels to America reveal how Europeans described
      a newly discovered "Other," and, indirectly, the "Self." Guy Poirier analyzes in
      his article how the images of acts against nature and prodigies could, at the
      same time, be linked to a European "episteme" and construct an ideological
      discourse of their own.

PMID- 8301088
TI  - Remembering lesbian bars: Montreal, 1955-1975.
AB  - This essay retraces the development of lesbian bars in Montreal between 1955 and
      1975. It analyzes this process as a form of appropriation of urban public space
      which reveals the repressive elements confronting lesbians in their pursuit of
      the right to exist socially, and examines the key-role played by working-class
      lesbians in struggling against them. It also describes class-related divisions in
      the way these places are remembered, which may be paralleled to the opposite
      positions in the current debate about the role of bars in the development of a
      lesbian culture. Finally, it suggests explanations for class-related differences
      in bar-going habits and ways of expressing lesbian identity.

PMID- 8301090
TI  - On a "minority complex".

PMID- 8301089
TI  - A game of appearances: the "ambigusexuality" in Brazilian culture of sexuality.
AB  - In this article I would like to present some aspects of the Brazilian culture of
      sexuality and I will do so in a comprehensive (Maffesoli, 1985) and
      constructivist way (Weeks, 1986). Therefore I will treat this subject of sexual
      orientation as something that has to be analysed in a historical and cultural
      context that particularly insists upon the specific context in which sexual
      orientation and gender role are found. The models of sexual behavior reflect the
      system of values and the social structure of society they are dealing with.
      Moreover, the perspectives of sexuality within a larger social universe, have to
      be seen as one of the numerous possible forms of behaviour. Consequently, in my
      opinion, it is very important for methodology, to use an approach that ceases to
      emphasize only the sexual aspect of homosocial relationships; they should be
      considered far more as one of the various ways of interpersonal relationships, in
      which sexualization is just one of all the possible facets (Aerts et al., 1983;
      Duyvendak and Mejer, 1988).

PMID- 8301091
TI  - The evolution of the AIDS illness and the polarisation of values.
AB  - This article is based on a study carried out in Sao Paolo, Brazil, from 1983 to
      1986 among male homosexuals. It deals with the various practices and life-styles
      which constitute the homosexual world in Sao Paulo, and questions regarding AIDS.
      An analysis is made of the contrasting biographies of two patients suffering from
      the AIDS virus. The emphasis will be placed on the evolution of the illness and
      the changes in values that occur during this period. The ways in which the sexual
      life-style adopted prior to the illness influences the individual social course
      or mobility [i.e., trajectory] of the inflicted person will also be illustrated.

PMID- 8301092
TI  - Homosexual rituals and safer sex.

PMID- 8301094
TI  - Bibliography of the current world literature in hypertension.

PMID- 8301093
TI  - Homosexuals and AIDS: a new approach to the illness.
AB  - AIDS, historically connected with homosexuals, has provoked a number of social,
      psychological, and moral reactions within the homosexual community itself as well
      as elsewhere. Among questions raised, there are all those concerning the meaning
      and place of human sexuality. Between strict moral condemnation and publicity for
      "Safer Sex," there is room for a personal ethic, reflection, and a more
      responsible behavior.

PMID- 8301095
TI  - The chymase-angiotensin system in humans.

PMID- 8301096
TI  - Guanine nucleotide regulatory protein alterations in the Milan hypertensive rat
      strain.
AB  - OBJECTIVE: To examine whether the altered regulation of adenylyl cyclase that has
      been reported in vascular tissues from spontaneously hypertensive rats is also
      evident in the Milan hypertensive (MHS) rat strain. DESIGN: The plasma membranes
      of vascular smooth muscle cells derived from thoracic aortae from adult (60-day
      old) MHS and Milan normotensive (MNS) strain rats were studied. METHODS: Guanine
      nucleotide regulatory protein (G-protein) function was inferred from adenylyl
      cyclase activity studies, and levels of G-protein subunits were assessed by
      immunoblotting. beta-Adrenergic receptor number and affinity were measured from
      the binding of the antagonist [125I]-cyanopindolol. RESULTS: Basal adenylyl
      cyclase activity was increased significantly in MHS rat cell membranes, and
      stimulation by 0.1 mmol/l isoproterenol and 0.01 mmol/l prostaglandin E1 was
      significantly greater in MHS than in MNS rat cell membranes. Forskolin (at 0.1
      mmol/l) resulted in a significantly greater stimulatory response in MHS
      membranes, which was eliminated by 0.01 mol/l NaF. Biphasic effects of GTP on
      isoproterenol-stimulated membranes demonstrated similar Gi function in MHS and
      MNS rat cell membranes, although a greater stimulatory GTP response was observed
      in MHS rat cell membranes. The levels of Gs alpha (both forms), Gi3 alpha and the
      beta-subunit were reduced in MHS rat cell membranes, whereas the levels of Gi2
      alpha and Gq alpha and G11 alpha were unchanged. The number of beta-adrenoceptors
      was increased significantly in MHS rat cell membranes, whereas receptor affinity
      for the antagonist was unaltered. CONCLUSIONS: There are differences in adenylyl
      cyclase stimulatory responses in MHS rat vascular smooth muscle cell membranes.
      We have found evidence of reduced levels of particular G-protein subunits,
      altered beta-adrenoceptor-Gs coupling and increased beta-adrenoceptor number.

PMID- 8301097
TI  - Action of dihydropyridine calcium antagonists on early growth response gene
      expression and cell growth in vascular smooth muscle cells.
AB  - OBJECTIVE: Evidence suggests that calcium antagonists may suppress vascular
      smooth muscle cell (VSMC) growth and proliferation, which may be a crucial step
      in the pathogenesis of hypertension and atherosclerosis. DESIGN: The effects of
      the dihydropyridine calcium antagonists nifedipine, nitrendipine, nisoldipine,
      nimodipine and isradipine on cell growth induced by platelet-derived growth
      factor (PDGF)-AB and angiotensin II (Ang II), and expression of the transcription
      factors c-fos and early-growth response gene 1 (egr-1) were investigated.
      METHODS: Proliferation of VSMC in culture was measured by [3H]-thymidine
      incorporation into cell DNA and by cell count. Expression of c-fos and egr-1
      messenger RNA (mRNA) was determined by the Northern blot technique. RESULTS: All
      of the calcium antagonists blunted the PDGF-induced rise in VSMC DNA synthesis.
      The inhibitory potency of isradipine on PDGF-stimulated DNA synthesis was
      approximately 10-fold that of the other calcium antagonists used, isradipine
      having a half-maximal inhibitory concentration (IC50) of (4.2 +/- 0.16) x 10(-7)
      mol/l. The calcium antagonists investigated also inhibited Ang II-induced DNA
      synthesis. Isradipine (10(-6) mol/l) completely abolished the PDGF-induced cell
      proliferation. Both PDGF (50 ng/ml) and Ang II (10(-7) mol/l) induced c-fos and
      egr-1 mRNA expression, having maximum effect after 30 min. In the case of c-fos,
      pre-incubation with 5 x 10(-6) mol/l isradipine led to a decrease in both Ang II-
      and PDGF-induced expression of this immediate-early gene. The expression of egr-1
      was not affected by pre-incubation with 5 x 10(-6) mol/l isradipine. CONCLUSIONS:
      All calcium antagonists investigated in the present study inhibited cell growth.
      Isradipine was more potent in blocking growth factor-induced cell growth than the
      other calcium antagonists studied. The inhibitory effect of the dihydropyridine
      calcium antagonists appears to be dependent on the expression of c-fos.

PMID- 8301099
TI  - Pharmacological study of SR 47436, a non-peptide angiotensin II AT1-receptor
      antagonist, in conscious monkeys.
AB  - OBJECTIVE: The hypotensive and hormonal responses of an AT1-subtype angiotensin
      II receptor antagonist, SR 47436, were investigated and compared with those of
      DuP 753 (losartan), the leading AT1-receptor antagonist, and captopril and
      enalapril, two major angiotensin converting enzyme (ACE) inhibitors, in
      conscious, sodium-replete and sodium-depleted non-human primates. DESIGN AND
      METHODS: Blood pressure and heart rate were measured in conscious, chronically
      instrumented sodium-replete (n = 3-5) and sodium-depleted (n = 4) cynomolgus
      monkeys (Macaca fascicularis). Plasma renin activity (PRA), active renin and
      angiotensin II plasma concentrations were determined. RESULTS: SR 47436 induced a
      dose- and time-related fall in blood pressure in sodium-depleted monkeys; the
      blood pressure-lowering effect was obtained at a range of doses from one-third to
      one-tenth the equihypotensive dose of DuP 753 after intravenous and oral
      administrations. The hypotensive effect obtained with SR 47436 was similar to
      that of captopril and was sustained in sodium-replete monkeys, although it was
      weaker and less long-lasting than that of enalaprilat. In both sodium-depleted
      and sodium-replete monkeys the AT1 antagonist and ACE inhibitors caused similar
      increases in PRA and active renin. However, although angiotensin II levels
      increased after SR 47436 or DuP 753 treatment, they decreased after treatment
      with enalaprilat. Modest decreases in the heart rate sometimes accompanied the
      hypotension, irrespective of the compound tested. CONCLUSION: These data
      demonstrate that the AT1 antagonist SR 47436 is an effective hypotensive agent in
      both sodium-replete and sodium-depleted monkeys, with an intrinsic potency three
      to 10 times that of DuP 753 and similar to that of ACE inhibitors.

PMID- 8301098
TI  - High blood pressure and metabolic disorders are associated in the Lyon
      hypertensive rat.
AB  - OBJECTIVE: A large population of F2 rats, obtained from a cross between male Lyon
      hypertensive (LH) rats and female Lyon normotensive (LN) rats, was studied in
      order to assess the relationship between increased body weight, hyperlipidaemia
      and high blood pressure which characterize LH rats. METHODS: Mean arterial
      pressure (MAP) was recorded in male, conscious, freely moving LH, LN, F1 and F2
      rats aged 30 weeks. Plasma total cholesterol, high-density lipoprotein-, low
      density lipoprotein- and very low-density lipoprotein-cholesterol, phospholipids,
      triglycerides, insulin and glucose were measured. RESULTS: In the F2 cohort it
      was observed that high MAP was a recessive trait that depends on several genes
      and was unrelated to body weight. The left ventricular weight, corrected for
      tibia length, was correlated with MAP. Plasma total and high-density lipoprotein
      cholesterol and phospholipids concentrations were lower in the F1 rats than in
      the LN rats, suggesting an overdominance of the LN alleles. In the F2 rats MAP
      was related to total, high-density lipoprotein- and low-density lipoprotein
      cholesterol. Plasma triglycerides, insulin and the insulin:glucose ratio, which
      were higher in the LH rats than in the LN rats, were also correlated with MAP in
      the F2 cohort. Using stepwise multiple regression analysis, MAP remained
      correlated with plasma total cholesterol, insulin and the insulin:glucose ratio,
      but not with triglycerides. CONCLUSIONS: Hypertension in LH rats is a recessive
      trait that is independent of body weight. In addition, the cosegregation of blood
      pressure with plasma cholesterol and, to a lesser degree, with insulin levels,
      which was observed in the present study provides the first direct evidence that
      these phenotypes are associated and are not due simply to genetic drift in the
      Lyon model.

PMID- 8301100
TI  - Nailfold capillary density in salt-sensitive and salt-resistant borderline
      hypertension.
AB  - OBJECTIVE: Nailfold capillary density was measured at rest and after 4 min
      circulatory arrest in order to investigate the relationship between sodium
      sensitive hypertension and microvessel density. DESIGN: Seventeen sodium
      sensitive and 28 sodium-resistant young borderline hypertensive males and 10
      normotensive controls were studied. All of the subjects ate a diet containing 120
      mmol/day sodium during the week preceding the investigation. METHODS: Capillary
      density was investigated by means of intravital video-microscopy. Blood pressure,
      cardiac index, plasma volume and humoral factors, such as plasma renin activity,
      plasma aldosterone and atrial natriuretic peptide, were also determined. RESULTS:
      No differences in capillary density were found under basal conditions. However,
      during hyperaemia the sodium-resistant subjects had significantly fewer perfused
      capillaries than both the sodium-sensitive and control subjects, whereas (apart
      from blood pressure) macrocirculatory parameters and humoral factors did not
      differ among the three groups. CONCLUSION: Sodium-resistant borderline
      hypertensives seem to be characterized by a (possibly structural) reduction in
      nailfold capillarity, a phenomenon that is, as yet, unexplained.

PMID- 8301101
TI  - Vascular distensibility and compliance in salt-sensitive and salt-resistant
      borderline hypertension.
AB  - OBJECTIVE: To gain insight into the relationship between vascular compliance and
      sodium sensitivity. DESIGN: Arterial and venous compliance was determined in 17
      sodium-sensitive and 28 sodium-resistant, young, borderline hypertensive males
      and in 10 age-matched normotensive controls, during regular sodium intake.
      METHODS: The carotid, femoral and brachial arteries were studied using a non
      invasive ultrasound vessel wall movement detector system, and venous compliance
      was determined using forearm strain-gauge plethysmography. Cardiac output, plasma
      volume and hormonal factors, such as plasma renin activity, were also measured to
      assess their possible influence on vascular compliance. RESULTS: Large artery
      compliance was significantly less in the sodium-sensitive than in the sodium
      resistant subjects in all arteries studied. Compared with controls, arterial
      compliance was reduced significantly in the sodium-sensitive group, whereas the
      sodium-resistant group did not differ significantly from the controls. Venous
      compliance was reduced equally in the two hypertensive groups compared with the
      controls, although the differences did not reach statistical significance.
      Cardiac output, blood pressure, plasma volume and hormonal factors did not differ
      between sodium-sensitive and sodium-resistant subjects and could not have been
      responsible for the observed differences in arterial compliance. CONCLUSIONS: The
      results of this study suggest that sodium-sensitive borderline hypertensives have
      reduced large artery compliance compared with age-matched sodium-resistant
      subjects. Since this finding could not be explained by differences in
      haemodynamic or hormonal factors between the groups, this suggests alterations to
      the viscoelastic properties of the arterial walls in sodium-sensitive subjects.

PMID- 8301102
TI  - Cyclosporin-induced hypertension precedes renal dysfunction and sodium retention
      in man.
AB  - OBJECTIVE: To study the acute effects of cyclosporin on blood pressure, renal
      function and hormones within the first few hours of drug ingestion in healthy
      man. DESIGN: A therapeutic (12 mg/kg) and a supratherapeutic (30 mg/kg) dose of
      cyclosporin were administered orally to 10 salt-replete normal healthy
      volunteers. Their renal haemodynamic parameters were assessed by inulin and para
      aminohippurate clearances, and their blood pressure was recorded every 20 min.
      RESULTS: Cyclosporin had an acute hypertensive effect while having no effect on
      sodium excretion or renal function. The earliest renal effect of cyclosporin was
      on water handling, with a marked antidiuretic effect. CONCLUSIONS: Our findings
      contradict previous data and currently held views regarding the pathogenesis of
      cyclosporin-induced hypertension. In particular, we have demonstrated that
      hypertension precedes any measurable change in renal haemodynamic parameters and
      occurs without apparent overall alterations in renal sodium excretion. We have
      also found that an antidiuresis is a very early renal effect of cyclosporin.

PMID- 8301103
TI  - Evidence for increased noradrenaline release from subcortical brain regions in
      essential hypertension.
AB  - OBJECTIVE: To test whether the activation of the sympathetic nervous system that
      is common in essential hypertension derives from subcortical noradrenergic
      neuronal excitation. DESIGN AND METHODS: We performed a radionuclide cerebral
      venous sinus scan, using technetium-99m, to establish which internal jugular vein
      predominantly drained the cortical (the major jugular vein) and which the
      subcortical (minor jugular vein) brain regions. Blood samples were then collected
      simultaneously from catheters placed percutaneously in the brachial artery or
      radial artery and high in the internal jugular vein in 11 untreated hypertensive
      patients and 18 normotensive subjects, for determination of the plasma
      concentrations of noradrenaline, its precursor dihydroxyphenylalanine (DOPA) and
      its metabolite dihydroxyphenylglycol (DHPG) to calculate their rates of overflow
      into the cerebrovascular circulation. RESULTS: In normotensive subjects blood
      flow determined by thermodilution was significantly higher in the major than in
      the minor jugular vein. The noradrenaline spillovers into the major and minor
      jugular veins calculated during infusions of L-[3H]-7-noradrenaline were similar
      in healthy subjects. The noradrenaline spillover from subcortical regions into
      the minor jugular vein was significantly higher in the hypertensives than in the
      normal subjects, as was the overflow of DHPG. In contrast, cortical noradrenaline
      and DHPG overflows into the major jugular vein were similar in hypertensive and
      normotensive subjects. Overflow of DOPA into the minor jugular vein, which
      derives largely from precursor turnover in dopaminergic neurons, was similar in
      hypertensive and normotensive subjects. Subcortical noradrenaline spillover
      correlated with neurochemical indices of sympathetic nervous system activity,
      with total body noradrenaline spillover (r = 0.56, P < 0.05) in normal and
      hypertensive subjects combined, and with renal noradrenaline spillover in the six
      hypertensive patients tested (r = 0.91, P < 0.05). CONCLUSION: These results
      suggest that increased subcortical noradrenaline release is a possible cause of
      peripheral sympathetic activation in essential hypertension.

PMID- 8301104
TI  - Indomethacin inhibits the effects of dietary supplementation with marine oils on
      vasoconstriction of human forearm resistance vessels in vivo.
AB  - OBJECTIVE: Dietary supplementation with marine oils attenuates the responses to
      noradrenaline and angiotensin II in human forearm resistance arteries. The
      mechanisms underlying these effects were the subject of the present study.
      METHODS: Twenty-two normal male adults were allocated to one of three groups. The
      first group (n = 11) received 10 g/day marine oil capsules (maxEPA) for 28 days.
      The second group (n = 7) received maxEPA plus 25 mg indomethacin three times a
      day on days 28 and 29. The third group (n = 4) received 10 g/day mixed-oil
      placebo capsules for 28 days, plus indomethacin on days 28 and 29 as in group 2.
      Forearm venous occlusion plethysmography was performed before and immediately
      after each treatment period. RESULTS: Responses to acetylcholine, sodium
      nitroprusside or reactive hyperaemia (area under the time-response curve: pre
      maxEPA 14,850 +/- 3502, post-maxEPA 17,118 +/- 4576 units) were unaffected by
      maxEPA. The suppressive effect of maxEPA on responses to noradrenaline and
      angiotensin II (from group 1) was no longer apparent in the group receiving
      indomethacin in addition to maxEPA. Indomethacin, in subjects on placebo
      capsules, had no effect on the responses to either agonist. CONCLUSION: We
      conclude that the suppressive effects of maxEPA result from alterations to in
      vivo prostanoid profiles.

PMID- 8301105
TI  - Parathyroid hypertensive factor-like activity in human essential hypertension:
      relationship to plasma renin activity and dietary salt sensitivity.
AB  - OBJECTIVE: To determine the clinical relevance of the newly described circulating
      pressor factor with parathyroid hypertensive factor (PHF)-like activity. DESIGN:
      Plasma samples were collected from 94 normotensive and 93 essential hypertensive
      subjects, the latter either previously defined by dietary salt sensitivity (n =
      43), or prospectively studied on both low- (< 50 mmol/day) and high-salt (> 200
      mmol/day) diets (n = 16). METHODS: Blood pressure, demographic factors, plasma
      renin activity (PRA), urinary electrolyte excretion and bioassayable PHF-like
      activity were determined in the fasted state on basal and altered dietary salt
      intakes. RESULTS: Among the normotensive subjects significantly higher PHF-like
      activity and reciprocally lower PRA values were observed in Black versus
      Caucasian subjects, particularly among females. In the hypertensive subjects PHF
      like activity levels were significantly elevated in the low- (17.1 +/- 1.5 mmHg,
      n = 34) and normal- (6.7 +/- 1.8 mmHg, n = 36) but not in the high-renin
      subgroups compared with values in the normotensive subjects (1.6 +/- 1.1 mmHg).
      Similarly, PHF-like activity values were significantly higher in salt-sensitive
      than in salt-insensitive hypertensives. Prospectively, PHF-like activity rose
      significantly with salt loading (4.9 +/- 1.2 to 20.4 +/- 6.2 mmHg) and was
      positively related (r = 0.648, P < 0.001) to the pressor response to salt.
      CONCLUSIONS: Elevated levels of PHF-like activity are characteristic of the low
      renin or salt-sensitive state, or both, and may contribute to the hypertensive
      process. Elevated PHF-like activity levels found in normotensive subjects may
      presage the development of low-renin, salt-sensitive hypertension.

PMID- 8301106
TI  - Low ventricular performance and high resistance in established hypertension in
      adults.
AB  - OBJECTIVE: To investigate the relationship between left ventricular performance
      and sympathetic nervous activity. DESIGN: We studied the alpha- and beta
      adrenergic responsiveness of the subjects and assessed their left ventricular
      performance. METHODS: Fifty-four adult established hypertensive patients, all
      with apparent left ventricular hypertrophy, and 36 age-matched normotensive
      controls were studied. Thirty-four of the hypertensive patients were within the
      +/- 2SD confidence area of fractional shortening/end-systolic stress relation of
      the normotensive controls and are denoted subgroup A; 19 patients were below the
      lower limit and are denoted subgroup B. Isoproterenol and neosynephrine injection
      tests were used to assess beta- and alpha-adrenergic responsiveness,
      respectively. Intravenous infusion tests using regitine and isoproterenol were
      performed in 16 patients to assess the effects of sympatho-adrenergic
      responsiveness on changes in left ventricular performance. RESULTS: Afterload and
      left ventricular mass were similar in the two subgroups. Left ventricular
      performance and beta-adrenergic responsiveness in subgroup A were comparable with
      the corresponding levels in the normotensives, whereas in subgroup B both were
      markedly decreased. The regitine infusion test induced a fall of 25% in
      peripheral resistance from baseline, but no significant improvement in left
      ventricular performance. In contrast, isoproterenol infusion test resulted in
      striking improvements: left ventricular performance increased by 60%, afterload
      decreased by 48% and peripheral resistance fell by 50% from baseline. CONCLUSION:
      The diminished ventricular performance and high resistance observed in adult
      established hypertension may be due to synergic effects of significantly reduced
      beta-adrenergic responsiveness coupled with enhanced alpha-adrenergic
      responsiveness.

PMID- 8301107
TI  - Evaluation of segmental elastic properties of the aorta in normotensive and
      medically treated hypertensive patients by intravascular ultrasound.
AB  - DESIGN AND METHODS: Local elastic properties of the descending aorta at different
      levels were evaluated by means of intravascular ultrasound images and pressure
      measurements. For this purpose, 30 normotensive patients and 30 age-matched
      medically treated patients with essential hypertension, all undergoing diagnostic
      cardiac catheterization, were studied. RESULTS: Hypertension was well controlled
      in the essential hypertensives (137.1 +/- 6.79/74.5 +/- 2.65 mmHg). Systolic but
      not diastolic blood pressure in the hypertensive patients was significantly
      different from that of the normotensives (118.8 +/- 4.38/69.7 +/- 1.65 mmHg). The
      continuous loss of volume compliance with increasing distance from the heart was
      significantly higher in the hypertensives than in the normotensive patients
      [normotensives (1.45 +/- 0.19) x 10(-10) m5/N at the thoracic aorta, (0.08 +/-
      0.05) x 10(-10) m5/N at the external iliac artery; hypertensives (0.81 +/- 0.09)
      x 10(-10) and (0.05 +/- 0.01) x 10(-10) m5/N at the corresponding sites].
      Similarly, the hypertensives had an elevated elastic modulus proximal to the
      aortic bifurcation compared with the normotensives (244.47 +/- 44.06 versus
      108.10 +/- 17.76 m/s, respectively). The decrease in buffering function of the
      vessel at this site is presumably caused by a turbulent flow pattern. Compared
      with the normotensives, the treated hypertensives had a significantly higher
      elastic modulus at each site where this was measured, whereas volume compliance
      and sectional compliance were lower. CONCLUSION: The differences in elastic
      modulus and compliance between hypertensive and normotensive patients seem
      disproportionate to the difference in systolic blood pressure (within the normal
      range in both the treated hypertensives and the normotensives). Therefore,
      normalization of high blood pressure by long-term antihypertensive treatment may
      not fully reverse changes, caused by arterial hypertension, in the viscoelastic
      properties of the arterial wall.

PMID- 8301109
TI  - Seasonal variation of blood pressure and its relationship to ambient temperature
      in an elderly population.
AB  - OBJECTIVE: To measure the magnitude and timing of seasonal variation of blood
      pressure and related factors in the elderly living in the community, and to
      assess their potential impact on cardiovascular risk. DESIGN: Prospective study;
      from January 1991 to February 1992 blood pressure and other variables were
      measured at 2-monthly intervals in each subject in their own homes. SUBJECTS:
      Ninety-six men and women, age range 65-74 years, recruited from a single group
      general practice in Cambridge. MAIN OUTCOME MEASURES: Seasonal variation of blood
      pressure, seasonal variation of prevalence of hypertension, seasonal variation of
      ambient temperature and body mass index. RESULTS: Both systolic (SBP) and
      diastolic blood pressure (DBP) were greatest during the winter across the whole
      distribution of blood pressure. There was a fourfold increase in the proportion
      of subjects with blood pressures > 160/90 mmHg in winter compared with in summer.
      Regression analysis revealed highly significant seasonal differences in both SBP
      and DBP. After adjustment for confounding seasonal effects, a 1 degree C decrease
      in living-room temperature was associated with rises of 1.3 mmHg in SBP and 0.6
      mmHg in DBP. CONCLUSIONS: Seasonal variation of blood pressure is heightened in
      older adults and may partly explain the greater cardiovascular disease mortality
      of elderly subjects during the winter. The blood pressures of elderly people may
      be inversely related to the ambient temperature. The public health implications
      of these findings deserve further investigation.

PMID- 8301108
TI  - Body fat distribution and left ventricular morphology and function in obese
      females.
AB  - OBJECTIVE: To study left ventricular function and morphology in non-hypertensive
      obese females and to relate the findings to body mass index (BMI) and to an index
      of body fat distribution (waist:hip ratio). DESIGN: Cross-sectional study.
      SETTING: Obesity unit in city hospital. SUBJECTS: Healthy obese females (n = 22)
      with BMI > 25 and < 40 kg/m2 and a non-obese, age-matched control group (n = 20)
      with BMI < 25 kg/m2. MAIN OUTCOME MEASURES: Blood pressure and non-invasive
      indices of left ventricular morphology and diastolic and systolic function.
      RESULTS: The obese group had significantly higher blood pressure, larger left
      ventricular end-diastolic diameter, greater left ventricular mass; larger left
      atrial size, signs of decreased left ventricular distensibility and prolonged
      left ventricular relaxation time index, and signs of supernormal systolic left
      ventricular function (as judged from the relationship between fractional
      shortening and end-systolic wall stress) than the non-obese controls. The results
      also indicated that left ventricular wall thickness and mass were well adapted to
      the increase in afterload, as judged by analyses of end-systolic wall tension and
      end-systolic wall stress. CONCLUSION: In confirmation of several previous
      studies, obesity was closely associated with an increase in blood pressure and
      left ventricular mass, and with early signs of disturbed left ventricular
      diastolic function. Left ventricular wall thickness and mass were well adapted to
      the increase in afterload; thus, we could not identify any non-afterload
      dependent effect of an increase in BMI or waist:hip ratio on left ventricular
      hypertrophy.

PMID- 8301110
TI  - Accutracker II (version 30/23) ambulatory blood pressure monitor: clinical
      validation using the British Hypertension Society and Association for the
      Advancement of Medical Instrumentation standards.
AB  - OBJECTIVE: To assess the Accutracker II (version 30/23) ambulatory blood pressure
      monitor by nationally agreed protocols in order to resolve previous conflicting
      assessments, and to examine the feasibility of combining these protocols into one
      study. DESIGN: The protocols of the Association for the Advancement of Medical
      Instrumentation (AAMI) and the British Hypertension Society (BHS) were used
      simultaneously. SUBJECTS: Five normotensive subjects were used to assess
      interobserver variation; 30 subjects took part in the field evaluation and 85 in
      the laboratory evaluation. The latter subjects were selected to cover a wide
      range of blood pressures and differences in arm circumference. OUTCOME
      MEASUREMENTS: Classification of device accuracy according to the criteria of the
      BHS and AAMI protocols. RESULTS: Among 255 observations the mean +/- SD
      difference between blood pressure measurements by the Accutracker II and the
      observers was -2.2 +/- 0.8/-3.5 +/- 0.9 mmHg. There was a small but statistically
      significant difference between one device and the other two, but all three
      fulfilled the BHS criteria of 95% of measurements falling within 3 mmHg before
      and after use. In 30 24-h recordings > 80% of the programmed inflations produced
      valid recordings. Editing criteria accounted for the majority (55%) of invalid
      readings; weak Korotkoff sounds, imperfect electrocardiogram signals or movement
      artefact accounted for the remainder. CONCLUSIONS: Version 30/23 of the
      Accutracker II fulfilled the AAMI criteria; using the BHS system, it was graded A
      for systolic and C for diastolic blood pressure. Although both protocols were
      readily combined into one study, they do not assess exactly the same aspects of
      blood pressure measurement. Previous conflicting evaluations could be due to
      differences in applying the protocols or may result from modifications in
      production models. Posture may affect the rating given by the BHS protocol. Until
      there is general international agreement on the method used to validate
      ambulatory blood pressure monitors, simultaneous use of both the BHS and AAMI
      protocols is recommended. In future assessments or investigational use of any
      similar instruments the model used should be described precisely.

PMID- 8301111
TI  - Short report: insertion variant in intron 9, but not microsatellite in intron 2,
      of the insulin receptor gene is associated with essential hypertension.
AB  - OBJECTIVE: To determine whether a microsatellite polymorphism of the insulin
      receptor gene (INSR) is associated with essential hypertension, as has been
      demonstrated previously for an Rsal restriction fragment length polymorphism
      (RFLP), and to examine blood pressure and plasma lipid profiles in relation to
      genotype. DESIGN AND METHODS: The study involved 75 Caucasian, non-diabetic
      hypertensive patients whose parents were both hypertensive, and 75 age-matched
      normotensive subjects whose parents were each normotensive after the age of 50
      years. Genotypes for the microsatellite polymorphism were determined for each
      subject using leucocyte DNA and a polymerase chain reaction method. Other
      parameters, including pretreatment blood pressure, body mass index and plasma
      lipids, were also determined. RESULTS: Comparison of microsatellite data for the
      eight genotypes and four alleles that were detected showed no significant
      difference by chi 2 analysis, either between the hypertensive and normotensive
      groups, or between obese and non-obese subgroups of hypertensives. This is in
      contrast to the significantly higher frequency seen for the R1- allele of an Rsal
      RFLP of INSR: 0.71 in the hypertensive group compared with 0.56 in the
      normotensive group. R1- allele frequency was elevated in all age groups of
      hypertensives and did not differ between obese and non-obese subgroups. The non
      obese hypertensives also had different plasma lipid profiles according to
      genotypes of the RFLP, with higher total and low-density lipoprotein-cholesterol
      in patients having the hypertension-associated R1- allele of the intron 9
      polymorphism. Moreover, systolic blood pressure was significantly greater in
      patients carrying the R1- allele and aged > or = 60 years. CONCLUSIONS: The
      present study allows definition of the hypertension-associated variants of INSR
      as those which are in linkage disequilibrium with a (CA)-repeat insertion
      polymorphism in intron 9 of the large, 22 exon, > 120-kb gene, but not those
      associated with a polymorphism in the second intron.

PMID- 8301112
TI  - Short report: ambulatory blood pressure in normotensive compared with
      hypertensive subjects. The Ad-Hoc Working Group.
AB  - OBJECTIVE: To delineate more precisely an operational threshold for making
      clinical decisions based on ambulatory blood pressure (ABP) measurement by
      studying the ABP in subjects who were diagnosed as either normotensive or
      hypertensive by conventional blood pressure (CBP) measurement. SUBJECTS: Twenty
      four research groups recruited 7069 subjects. Of these, 4577 were normotensive
      (CBP < or = 140/90 mmHg), 719 were borderline hypertensive (systolic CBP 141-159
      mmHg or diastolic CBP 91-94 mmHg) and 1773 were definitely hypertensive. Of the
      subjects in the last of these categories, 1324 had systolic hypertension
      (systolic CBP > or = 160 mmHg) and 1310 had diastolic hypertension (diastolic CBP
      > or = 95 mmHg). Hypertension had been diagnosed from the mean of two to nine
      (median two) CBP measurements obtained at one to three (median two) visits.
      RESULTS: The 95th centiles of the 24-h ABP distributions in the normotensive
      subjects were (systolic and diastolic, respectively) 133 and 82 mmHg. Of the
      subjects with systolic hypertension, 24% had 24-h systolic ABP < 133 mmHg.
      Similarly, 30% of those with diastolic hypertension had 24-h diastolic ABP < 82
      mmHg. The probability that hypertensive subjects had 24-h ABP below these
      thresholds tended to increase with age and was two- to fourfold greater if the
      CBP of the subject had been measured at only one visit and if fewer than three
      CBP measurements had been averaged for establishing the diagnosis of
      hypertension. By contrast, for each 10-mmHg increment in systolic CBP, this
      probability decreased by 54% for 24-h systolic ABP and by 26% for 24-h diastolic
      ABP, and for each 5-mmHg increment in diastolic CBP it decreased by 6 and 9%,
      respectively. CONCLUSIONS: The ABP distributions of the normotensive subjects
      included in the present international database were not materially different from
      those in previous reports in the literature. One-fifth to more than one-third of
      hypertensive subjects had an ABP which was below the 95th centile of the ABP of
      normotensive subjects, but this proportion decreased if the hypertensive subjects
      had shown a higher CBP upon repeated measurement. The prognostic implications of
      elevated CBP in the presence of normal ABP remain to be determined.

PMID- 8301113
TI  - Ligation of CD45 on B cells can facilitate production of secondary Ig isotypes.
AB  - The possibility that isotype switching in B cells may be affected by engagement
      of the CD45 molecule on B cells has been investigated in microcultures containing
      limiting numbers of B cells and nonlimiting numbers of both alloreactive Th cells
      and purified dendritic cells (DC). Addition of Abs to the B cell-specific
      isoform, B220, to the microcultures leads to an increase in the proportion of B
      cell clones that secrete secondary Ig isotypes. In the presence of anti-CD45 Ab,
      microculture wells show a 39% frequency of secondary isotypes (560/1440) compared
      with a 11% frequency in control microcultures (89/780). Cross-linking appears to
      enhance this effect. Even in cultures of B cells and DC without T cells, addition
      of anti-B220 induces isotype switching in a significant number of microwells.
      Cross-linking and capping B220 molecules results in co-capping of surface Ig and
      MHC class II molecules. The results suggest that signal transduction through the
      CD45 molecule may affect pathways involved in isotype switching.

PMID- 8301114
TI  - Thymic epithelial cell lines that mediate positive selection can also induce
      thymocyte clonal deletion.
AB  - Negative selection of potentially autoreactive thymocytes occurs mainly in the
      thymus and is thought to be induced primarily by interaction with bone marrow
      derived cells. However, some studies have also reported a role for radioresistant
      thymic cells, which are probably epithelial in origin, in the deletion of
      thymocytes reacting to endogenous superantigens. We have previously demonstrated
      that thymic epithelial cell lines could induce thymocyte-positive selection in
      vivo. In this study, we assessed the potential of these cells to delete
      thymocytes reacting to the staphylococcal enterotoxin A or B superantigens in
      vitro. In the presence of staphylococcal enterotoxin A or B we found that all
      thymic epithelial cell lines used in this study were capable of activating T cell
      hybrids or deleting CD4+CD8+ thymocytes expressing an appropriate TCR. The extent
      of superantigen-mediated thymocyte deletion mediated by thymic epithelial cell
      lines was comparable to that mediated by a thymic macrophage cell line. Similar
      results were obtained with three phenotypically distinct thymic cell lines,
      suggesting that the ability to induce thymocyte deletion might be a general
      feature of various subsets of thymic epithelium. The observations provided in
      this study, combined with our previous demonstration that the same thymic
      epithelial cell lines can participate in positive selection, suggest that a given
      stromal cell population might be capable of taking part both in positive and
      negative selection of thymocytes.

PMID- 8301115
TI  - Tissue-specific expression of messenger RNAs encoding endogenous viral
      superantigens.
AB  - The minor lymphocyte stimulating (MLS) superantigens of mice are encoded by open
      reading frames (ORFs) in the 3' long terminal repeats (LTRs) of endogenous mouse
      mammary tumor viruses. By stimulating all T cells bearing particular TCR V beta
      proteins, these viral superantigens (v-SAGs) exert profound effects on T cell
      development and function. We have examined expression of the 1.7 kb mRNA product
      predicted to encode v-SAG proteins in different cells and tissues of the immune
      system. The LTR-ORF mRNA was expressed in activated B cells and activated mature
      CD8 but not CD4 T cells, consistent with previous functional studies assessing
      MLS activity in these cell types. Little or no message was detected in thymic
      epithelial cells, macrophages, or dendritic cells, although low levels could be
      observed in thymic epithelium after southern hybridization to PCR-amplified cDNA.
      LTR-ORF mRNA was also expressed in immature CD4-CD8- and CD4+CD8+ thymocytes,
      suggesting selective down-regulation of expression in the T cell lineage after
      differentiation to the CD4+ phenotype. Thus, among cells of the immune system, v
      SAG encoding mRNA is expressed predominantly within the lymphoid lineage.

PMID- 8301116
TI  - Expression of Mtv-7 sag gene in vivo using a retroviral vector results in
      selective inactivation of superantigen reactive T cells.
AB  - T cells expressing specific TCR V beta chains are intrathymically eliminated in
      mice expressing the murine Mls (minor lymphocyte stimulating) superantigens.
      Recently, in vitro studies have shown that the endogenous mouse mammary tumor
      virus (MMTV)-7 sag gene encodes Mls-1 Ag. The demonstrated ability of MMTV
      superantigen proteins to react with TCRs has led to the postulate that other
      infectious retroviruses may use superantigen-like molecules to modify the host's
      immune system. In this report, successful retrovirus-mediated Mtv-7 sag gene
      transfer into pluripotent hematopoietic stem cells is described. In two different
      strains of Mls-1- host mice (CBA/Ca and BALB/c) reconstituted with Mtv-7 sag gene
      expressing bone marrow cells, low levels of ectopic Mtv-7 sag gene expression on
      syngeneic donor hematopoietic stem cell-derived population alone can induce
      partial clonal deletion of Mls-1 reactive V beta 6+ and V beta 8.1+ T cells, and
      complete clonal inactivation of V beta 8.1+ T cells.

PMID- 8301117
TI  - Unique phenotype and distinct TCR V beta repertoire in human peripheral blood
      alpha beta TCR+, CD4-, and CD8- double negative T cells.
AB  - TCR-alpha beta+ CD4- CD8- double-negative (DN) T cells represent a small, poorly
      defined T cell subset in human peripheral blood that has been postulated to be
      potentially autoreactive. To define some of the characteristics of this subset of
      T cells, DN cells and CD4+ and CD8+ single-positive (SP) cells were purified from
      the peripheral blood of six unrelated individuals by a combination of positive
      selection and depletion using mAb conjugated to immunomagnetic beads. Purified DN
      cells were found to be enriched in cells expressing HLA-DR and the NK cell
      marker, CD56, when compared to the SP population. Furthermore, in contrast to SP
      cells that express the adhesion marker CD44, DN cells were found to express very
      little, if any, CD44. When the V beta TCR repertoires of DN and SP (CD4+ and
      CD8+) cells, determined by quantitative (q) PCR, were compared all three
      populations were found to be considerably different. Furthermore, several V beta
      segments (V beta 11 and V beta 19) were consistently expressed at higher levels
      on DN cells than on SP cells. The TCR repertoires of both DN and SP cells were
      frequently characterized by dominance of one or more V beta segments that could
      in some instances be shown to be restricted to the CD45RO+ ("memory") population.
      However, differences in TCR repertoire between DN and SP cells were observed even
      when CD45RO+ cells were removed before qPCR analysis. These studies suggest that
      the TCR repertoires of DN and SP cells are determined by different selection
      mechanisms and that DN and SP cells are directed against different Ag.

PMID- 8301118
TI  - Peptide binding to surface class II molecules is the major pathway of formation
      of immunogenic class II-peptide complexes for viable antigen presenting cells.
AB  - Although studies on fixed APCs have demonstrated that peptide can bind to cell
      surface class II molecules, the mechanisms by which peptide-class II complexes
      are formed in viable cells is largely unexplored. To explore the possibility that
      peptide loading of class II molecules was occurring after endocytosis of peptides
      as well as by surface binding, we utilized an immunogenic hemagglutinin peptide
      (HAP 128-145) from the influenza strain A/Japan/57, and studied the appearance of
      surface complexes of HAP 128-145 bound to HLA-DRw11 molecules on human B
      lymphoblastoid cells (BLCLs). Detection of the bound peptide was made possible by
      a rabbit anti-serum (alpha HAP) raised against HAP 128-145, which recognizes both
      the free peptide as well as peptide bound to DRw11 on living APCs. Pretreatment
      of the BLCLs with a variety of inhibitors of protein synthesis and intracellular
      trafficking failed to decrease the levels of HAP 128-145/DRw11 surface complexes.
      However, significant inhibition in the appearance of these complexes was caused
      by a decrease in the temperature at which the cells were incubated with peptide.
      Temperature-specific inhibition was also observed for fixed DRw11-positive APCs
      and purified DRw11 molecules indicating that the effect of temperature was
      directly on the class II molecules. We conclude that surface binding of peptide
      by class II molecules on human B cells is a major pathway of formation of
      immunogenic class II-peptide complexes for at least some soluble antigenic
      peptides, and that endocytosis of soluble peptides with subsequent binding of
      peptide by intracellular class II molecules plays little if any role in the
      formation of such complexes. Moreover, class II molecules have evolved to stably
      bind peptide optimally at physiologic temperatures, independent of cell
      metabolism.

PMID- 8301119
TI  - Reduction of CTL antipeptide response mediated by CD8+ cells whose class I MHC
      can bind the peptide.
AB  - Primary CTL responses can be generated in vitro against defined peptides in
      association with class I MHC molecules. We show here that if cells obtained from
      a 5-day MLR are also included in the cultures, the response is greatly reduced if
      the added cells both carry CD8 and can bind the peptide. Our interpretation is
      that the added MLR cells are acting as deletional APC or veto cells. Peptide
      specific CTL precursors recognize the peptide on the class I MHC of the CD8+ MLR
      cells and then receive a negative signal via CD8 on these cells. In support of
      this, when MLR cells carrying the Lyt-2.1 allele of CD8 were used to down
      regulate the response of Ly-2.2+ responder cells, inclusion of anti-Ly-2.1 mAb in
      the cultures partially reversed the response reduction. Similar signaling may
      occur in vivo. When mice were injected i.v. with syngeneic lymphoid cells
      incubated with a peptide which they could bind, the response against that peptide
      was specifically reduced in a subsequent in vitro assay.

PMID- 8301120
TI  - Immunization with soluble hepatitis B virus surface protein elicits murine H-2
      class I-restricted CD8+ cytotoxic T lymphocyte responses in vivo.
AB  - Immunization with soluble proteins only rarely induces a specific response of
      CD8+ CTL. We describe experiments that demonstrate the efficient and specific in
      vivo priming of CTL in BALB/c mice immunized with soluble hepatitis B virus (HBV)
      derived surface (S) protein. A single (s.c., i.p. or i.v.) injection of a low
      dose (30 ng to 3 micrograms per mouse) of recombinant S protein particles without
      adjuvants induced a CTL response. This specific cytotoxic response was read out
      against a panel of different S protein-expressing transfected mouse cell lines.
      Effector cells of this response were Ld-restricted, CD3+ CD4- CD8+ CTL. H-2d/Ld+
      (BALB/c, C.B-17) mice were responders; H-2d/Ld- (dm2) mutant mice and H-2b
      (C57BL/6) mice were nonresponders. Injections of various dosages of a S protein
      derived, immunogenic, synthetic peptide into BALB/c mice by various routes did
      not prime CTL. After incorporation of S protein particles into IFA or aluminum
      hydroxide, these protein Ag lost their ability to specifically stimulate CTL in
      vivo. After priming of mice with S protein emulsified in IFA or adsorbed to
      aluminum hydroxide boost injections with native S protein particles were
      inefficient in stimulating a specific CTL response. These findings are of
      relevance for the design of synthetic subunit vaccines for which specific
      stimulation of CD8+ T effector functions is desired.

PMID- 8301121
TI  - The novel mAb QR6.6 detects a surface molecule on immature thymocytes and
      inhibits their proliferation on thymic epithelial cells.
AB  - We previously reported that the nude mouse-derived splenic T cell clone N-9F
      exhibits a proliferative response when cultured on thymic stromal cells. This N
      9F proliferation is mediated by direct cell-to-cell interactions between T and
      thymic stromal cells. A thymic epithelial cell clone, SL10.3, also supports N-9F
      growth. To identify the molecule involved in T cell development in the thymus, we
      established mAb specific to the N-9F clone. One of these mAb, QR6.6, was found to
      inhibit the N-9F proliferative response on SL10.3. QR6.6-positive cells were
      detected in thymus but not in other lymphoid organs such as bone marrow, lymph
      nodes, or spleen. QR6.6-positive cells accounted for 3 to 5% of the cells in
      adult thymuses whereas higher percentages were found in neonatal (10-20%) and
      fetal thymuses (70% at E17 and 10-20% at E15). The positive cells were primarily
      CD4-8- thymocytes in fetuses and CD4-8- to CD4+8+ thymocytes in adults. The QR6.6
      mAb precipitates a 100 kDa molecule from the N-9F clone. The addition of the mAb
      to fetal thymus organ culture reduces the recovery of cells at culture day 4. It
      was also found that the mAb inhibits fetal thymocyte proliferation on the SL10.3
      thymic epithelial cell line. These results suggest that the 100 kDa molecule
      detected by the QR6.6 mAb may play a crucial role in the early stage of thymocyte
      development.

PMID- 8301123
TI  - Testing the importance of each residue in a HLA-B27-binding peptide using
      monoclonal antibodies.
AB  - When a peptide derived from histone 3.3 was incubated with mouse L cells
      transfected with HLA-B27, the cells became highly reactive with Ye-2, an anti-HLA
      B27 mAb. The critical residues were analyzed by testing analogues in which each
      of the nine residues in the peptide was consecutively substituted by 19 other
      amino acids. The conclusions were separately verified using a different HLA-B27
      positive cell line. The ability of some of these peptides to bind to HLA-B27 was
      also assayed by their ability to stabilize HLA-B27 in a mutant cell line which
      required HLA-B27-binding peptides to express HLA-B27 at 37 degrees C. These
      experiments showed that in P4, P5, P6, P7, P8, and P9, all 20 different amino
      acids could be substituted without eliminating the ability of the analogues to
      bind to HLA-B27. The residues which were responsible for the HLA-B27-peptide
      complex reacting with the Ye-2 antibody were P8 and P9. The latter might mediate
      its effect by altering either the surface conformation of the closely associated
      HLA-B27 heavy chain or the conformation of the peptide itself.

PMID- 8301122
TI  - MHC-encoded proteasome subunits LMP2 and LMP7 are not required for efficient
      antigen presentation.
AB  - LMP2 and LMP7 are proteins encoded by MHC genes that are tightly linked to the
      genes encoding TAP, the transporter that conveys peptides from the cytosol to the
      endoplasmic reticulum for assembly with MHC class I molecules. LMP2 and LMP7 are
      subunits of a subset of proteasomes, large molecular assemblies with multi
      proteolytic activities believed to degrade damaged and unwanted cellular
      proteins. Like TAP and class I molecules themselves, expression of LMP genes is
      enhanced after exposure of cells to IFN-gamma. These findings implicate LMP2 and
      LMP7 in the cytosolic production of antigenic peptides. Doubts have been cast,
      however, on the role of LMP2 and LMP7 in Ag processing, because cells lacking
      these proteins possess class I molecules that contain peptides quantitatively and
      qualitatively indistinguishable from the peptides bound to class I molecules
      derived from normal cells. In this paper we show that cells lacking LMP2 and LMP7
      present seven TAP-dependent determinants derived from viral proteins. For two
      determinants, the kinetics of presentation are shown to be similar for LMP
      expressing and -nonexpressing cells. We also demonstrate biochemically that
      peptide is not limiting in the assembly of class I molecules in LMP-nonexpressing
      cells. These findings provide additional evidence that LMP2 and LMP7 are not
      required for efficient Ag presentation, and suggest that these proteins have
      either a more specialized role in the production of class I-associated peptides,
      or are not involved in the processing of proteins for association with class I
      molecules.

PMID- 8301124
TI  - A monoclonal antibody that recognizes HLA-B27 in the context of peptides.
AB  - The T2 mutant cell line is unable to load peptides into the MHC class I Ags
      inside the cells. These "empty" MHC class I Ags are not expressed on the cell
      surface unless the cells are cultured at low temperatures. Expression will occur
      at 37 degrees C only in the presence of peptides that bind to and stabilize the
      class I Ags. T2 cells transfected with the B*2705 gene were tested with a panel
      of anti-HLA-B27 mAb. Two of the antibodies, ME1 and KS3, reacted with the "empty"
      HLA-B27 expressed at low culture temperatures. Three antibodies, B27.M1, B27.M2,
      and Ye-2, were unreactive with these "empty" HLA-B27. The cells were then
      incubated with a panel of HLA-B27-binding peptides. One of the antibodies, Ye-2,
      became reactive when the cells were incubated with a peptide derived from HIV
      gp120 and to a less degree with a peptide derived from histone H3.3. Mouse L
      cells transfected with the B*2705 and the human beta 2m genes also reacted very
      poorly with B27.M1, B27.M2, and Ye-2. Those two peptides were also able to induce
      high increase in Ye-2 reactivity. Alternately, increase in Ye-2 reactivity was
      also observed when the L cells were incubated with IFN-gamma or TNF-alpha. These
      experiments indicate that the Ye-2 anti-HLA-B27 mAb recognizes HLA-B27 in the
      context of certain residing peptides either added exogenously or expressed
      endogenously. The B27.M1 and B27.M2 antibodies might share similar
      characteristics.

PMID- 8301125
TI  - Mapping of amino acid residues in the C mu 3 domain of mouse IgM important in
      macromolecular assembly and complement-dependent cytolysis.
AB  - By analyzing the effects of single site mutations of a TNP-binding mouse IgM we
      have identified amino acid residues clustered in two regions in the C mu 3 domain
      that are important in the complement-dependent cytolytic activity of polymeric
      IgM. Some of the mutations also impaired IgM polymerization. For one of these
      clusters, D432G, P434A, and P436S, which lies on the fy2 and fy3 strands and
      their connecting loop, polymerization was little affected and the effect on the
      cytolytic activity of the polymer fraction was taken to imply direct involvement
      of the residue in C1 binding. The other cluster, involving residues D356A K361A
      and D417G, is situated at the other end of the C mu 3 domain closer to the center
      of the Fc mu disc. The D356A K361A and D417G mutations significantly impaired
      polymer formation, suggesting that these residues are necessary for proper
      folding or packing of the C mu 3 domains and may affect cytolysis only
      indirectly. Some other mutations had little or no effect on polymerization or
      cytolytic activity (E423A, E527G), whereas some mutations impaired only IgM
      polymerization without affecting cytolytic activity (D344A, K361A, K443A P544G).
      In others the defect in polymerization was so profound that only the monomer
      formed (H430A/N/Q and K438G). Our results also suggest that the C1 binding site
      of IgM is not strictly homologous to the C1 binding site of IgG. Although
      mutation of E318 of IgG has been shown to reduce its cytolytic activity, mutation
      of the homologous residue in IgM, E423, was without effect as were mutations of
      other flanking-charged residues. Proline at 436 in IgM and 331 in IgG may,
      however, be a common element.

PMID- 8301127
TI  - Influence of coding region polymorphism on the peripheral expression of a human
      TCR V beta gene.
AB  - A number of human TCR V beta gene segments are reported to be polymorphic, with
      alleles differing by one or a small number of amino acid substitutions. In the
      absence of detailed structural information regarding the interaction of specific
      positions in the TCR with Ag or MHC, the significance of such variation is
      difficult to assess. In this report the relative use of the two common alleles of
      the human V beta 6.7 gene, 6.7a and 6.7b, which differ by two non-conservative
      amino acid substitutions, and the use of two common alleles of the V beta 12.2
      gene, which differ by only silent substitutions, were measured in PBL derived
      from individuals heterozygous for these alleles. Equal use of V beta 12.2 alleles
      was observed, consistent with the inability of selection mechanisms to
      discriminate between the products of these alleles that are indistinguishable at
      the amino acid level. However, statistically significant skewing in the use of V
      beta 6.7 alleles was observed in 15 of 16 individuals studied. Expression levels
      for each allele ranged from 16 to 84% of the total V beta 6.7 signal in
      heterozygous individuals, with either the 6.7a or the 6.7b allele predominant in
      different individuals. Based on segregation studies in families, it seems
      unlikely that other unidentified polymorphism in the TCR beta locus, such as in
      the V beta 6.7 promoter, was responsible for the differential allele expression.
      Family studies provided no evidence for an association between specific HLA
      haplotypes and V beta 6.7 allele use. These results indicate that even modest
      allelic variation in human TCR V beta coding regions can have a significant
      impact on the expression of human V beta genes in the peripheral repertoire.

PMID- 8301126
TI  - Analysis of mutant HLA-A2 molecules. Differential effects on peptide binding and
      CTL recognition.
AB  - Previous studies have identified several residues lining the groove of the HLA
      A2.1 molecule that are critical for Ag presentation. However, it is not clear
      whether these residues are critical for binding of the peptide epitope per se or
      for determining the appropriate conformation of bound peptide. To distinguish
      between these possibilities, mutations at eight of these residues have been
      tested for their effects on the ability of the molecule to bind and present two
      known peptide epitopes--one derived from the influenza A matrix protein, the
      other from HIV pol. With only one exception, the mutations were found to affect
      the binding of the two peptides similarly. Most of the mutations resulted in
      intermediate deleterious effects on binding, with the B pocket mutant F9Y having
      the most dramatic negative effect on binding for both peptides. Two of the
      mutations significantly enhanced binding of both peptides and a peptide-specific
      effect on binding was seen with the substitution, Y99H, which enhanced binding of
      the matrix peptide yet diminished binding of the pol peptide. In contrast to the
      effects on binding, the effects of the mutations on presentation differed
      considerably for the two peptides. The most striking difference was seen with two
      alpha 2 alpha helix mutants that are fully recognized by pol peptide-specific CTL
      but not recognized by matrix peptide-specific CTL even though levels of binding
      were comparably diminished for the two peptides. These results suggest that some
      interactions, although not critical for binding per se, are critical for
      functional binding and the importance of these interactions differs among peptide
      epitopes.

PMID- 8301128
TI  - The mouse CD69 gene. Structure, expression, and mapping to the NK gene complex.
AB  - CD69 is a rapidly induced T cell activation Ag that is also expressed in an
      inducible fashion on cells of most, if not all, hematopoietic lineages. Molecular
      cloning has shown that CD69 is a type II membrane glycoprotein that is a member
      of the C-type lectin family. In this report we have shown that induction of CD69
      mRNA in activated murine thymocytes and T cells is very rapid, peaking between 30
      and 60 min poststimulation, and transient, dropping to nearly resting levels by 8
      h. An analysis of the mouse CD69 gene structure showed the gene to consist of 5
      exons and have a phorbol ester-inducible promoter element within the first 700 bp
      upstream of the start of transcription. Chromosomal mapping placed the mouse CD69
      gene on the long arm of chromosome 6 near the NK gene complex that contains the
      related NKR-P1 and Ly-49 gene families. The human CD69 gene mapped to chromosome
      12p13 near the related NKG2 gene cluster and in a region associated with
      rearrangements in approximately 10% of cases of childhood acute lymphocytic
      leukemia.

PMID- 8301129
TI  - Human microglial cell defense against Toxoplasma gondii. The role of cytokines.
AB  - Microglia may play an important role in host defense of the central nervous
      system against Toxoplasma gondii, and cytokines produced by these glial cells may
      participate in their antitoxoplasma activity. In our study, the antitoxoplasma
      activity of human fetal microglia was investigated. The RH strain of T. gondii
      multiplied readily in these glial cells. IFN-gamma/LPS-treated microglia limited
      (p < 0.01) T. gondii growth by reducing entry of this parasite rather than
      intracellular multiplication. More than 90% of the antitoxoplasma activity of
      activated microglia was blocked (p < 0.01) by neutralizing antibodies to TNF
      alpha or IL-6 (but not to IL-1 or TGF-beta), suggesting that these
      proinflammatory cytokines play a role in the inhibitory process. Consistent with
      this hypothesis, treatment of microglia with TNF-alpha or IL-6 (in the presence
      or absence of IFN-gamma) inhibited (p < 0.01), in a dose-dependent manner, T.
      gondii growth. Inasmuch as NGMA did not affect cytokine-mediated antitoxoplasma
      activity of microglia, nitric oxide appears not to be involved in this host
      defense function of human fetal microglia. Results of our study suggest that the
      host defense activity of human microglia against T. gondii is dependent primarily
      on the activating properties of IFN-gamma, TNF-alpha, and IL-6.

PMID- 8301130
TI  - Human monocyte infection by Leishmania (Viannia) panamensis. Role of complement
      receptors and correlation of susceptibility in vitro with clinical phenotype.
AB  - Peripheral blood monocytes (PBMs) from healthy individuals who had experienced
      distinctive clinical outcomes after natural infection with Leishmania (Viannia)
      were evaluated in vitro with respect to susceptibility to infection by stationary
      phase promastigotes of L. (V). panamensis. Concomitantly, the role of complement
      receptors (CR) CR1 and CR3 in the attachment and entry of L. (V). panamensis into
      human monocytes was analyzed using mAbs to CR1 (CD35) and CR3 (CD11b) to inhibit
      competitively these early events in the host-parasite interaction. Cell adherence
      to fibronectin was examined to determine how modulation of CR activity affected
      the attachment and uptake of this parasite species. The human monocyte cell line
      U-937 was also evaluated and found to provide a reproducible control for L. (V).
      panamensis infection in vitro. Opsonization with fresh AB+ serum markedly
      enhanced uptake by both PBMs and U-937 cells, and the fluid phase blocking of CR1
      and CR3 resulted in partial inhibition of attachment and/or internalization.
      Uptake rather than attachment was abrogated by antireceptor antibodies in PBMs
      from previously infected individuals, whereas attachment was diminished in PBMs
      from unexposed controls. Adherence of PBMs to fibronectin resulted in decreased
      infection. PBMs from persons who had experienced chronic disease 5 to 8.4 yr
      before these studies were significantly more susceptible to in vitro infection by
      L. (V). panamensis than PBMs from asymptomatically infected or control
      individuals based on the percentage of cells infected, the number of parasites
      per cell, and viability of intracellular parasites at 48 h postinfection. Neither
      blocking of CR nor modulation by fibronectin altered the pattern of
      susceptibility of PBMs from the different clinical groups. These findings provide
      evidence for the participation of CR in the infection of human monocytes by L.
      (V). panamensis and demonstrate a correlation between clinical phenotype and in
      vitro infection of PBMs cultured in the presence of autologous plasma before
      experimental infection.

PMID- 8301131
TI  - Stimulation of tumor-draining lymph node cells with superantigenic staphylococcal
      toxins leads to the generation of tumor-specific effector T cells.
AB  - In animal studies, lymph nodes (LN) draining progressive tumors contain
      immunologically sensitized but functionally deficient T cells. These preeffector
      cells can differentiate into mature effector cells on stimulation in vitro with
      anti-CD3 and IL-2. However, anti-CD3 react with all T cells and the activated
      cell population expressed a broad but normal distribution of V beta phenotypes.
      In this study, we examined the feasibility of using bacterial superantigens to
      stimulate tumor-draining LN cells. Because of their TCR V beta restriction,
      superantigen activation may afford a means to identify T cell subsets that are
      important in the antitumor immune response. Stimulation of draining LN cells with
      staphylococcal enterotoxins A (SEA) or B (SEB) followed by culture in IL-2
      resulted in selective activation and expansion of V beta 3 and V beta 11 or V
      beta 3 and V beta 8 T cells, respectively. However, in adoptive immunotherapy,
      SEB- but not SEA-activated cells mediated the regression of established pulmonary
      metastases. To define the relative antitumor effects of V beta 3 and V beta 8 T
      cells, SEB-activated cells were depleted of either V beta 3 or V beta 8 T cells
      with mAb and magnetic beads. The antitumor effects were demonstratably diminished
      after V beta 8 cell depletion but enhanced after V beta 3 cell depletion. Using
      antigenically distinct MCA 205 and 207 sarcomas, tumor regression mediated by the
      activated cells was found to be immunologically specific for the tumor that
      stimulated the draining LN. Furthermore, the SEB-activated cells were virtually
      all T cells consisting of approximately equal proportions of CD4+ and CD8+ cells
      and the collaboration of the two T cell subsets was required for in vivo
      antitumor effects. However, the helper function of CD4+ cells could be
      facilitated by the administration of exogenous IL-2. Despite their in vivo
      antitumor reactivity, SEB-activated cells did not exhibit tumor cytotoxicity in
      the 4-h 51Cr release assay. However, they secreted IFN-gamma on specific
      stimulation with tumor cells. Taken together, these results provide for the first
      time clear evidence of the functional significance of superantigen interactions
      with immunologically committed T cells and suggest a preferential V beta use that
      might be associated with the T cell immune response to progressively growing
      tumors.

PMID- 8301132
TI  - Intracerebral cytokine mRNA expression during fatal and nonfatal alphavirus
      encephalitis suggests a predominant type 2 T cell response.
AB  - Sindbis virus (SV) causes an acute encephalomyelitis in mice. A T cell-dependent
      inflammatory response is first detected 3 days after infection and includes T
      cells, B cells, and macrophages. The cytokines produced locally by intrinsic
      cells of the brain in response to infection and by infiltrating mononuclear cells
      and their contributions to outcome of infection have not been identified.
      Semiquantitative reverse transcriptase-PCR was used to evaluate the expression of
      mRNAs for IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, leukemia inhibitory
      factor (LIF), and TGF-beta in the brain during fatal and nonfatal SV encephalitis
      of immunocompetent BALB/cJ and immunodeficient scid/CB17 mice. IL-1 beta and IL-6
      mRNAs were detected in uninfected mice before infection and were up-regulated
      within 24 h. TGF-beta mRNA was also constitutively expressed in uninfected mice.
      LIF mRNA was occasionally detected in uninfected mice but increased in amounts
      only in BALB/cJ not scid mice after infection. TNF-alpha, IL-4, and IL-10 mRNAs
      were not found in uninfected mice but were induced within 24 h and continued to
      rise through 7 days after infection with substantially higher levels in BALB/cJ
      than scid mice. These data suggest that intrinsic brain cells produce IL-1, IL-4,
      IL-6, IL-10, LIF, and TGF-beta mRNAs in response to viral infection. IFN-gamma
      and IL-2 mRNAs were detected only in BALB/cJ mice and not until 3 days after
      infection with the initiation of inflammation. IL-4 and IL-10 mRNAs were more
      persistent and more easily detectable than IL-2 and IFN-gamma mRNAs. These data
      suggest a predominant type 2 cytokine response in the brain during SV
      encephalitis. BALB/cJ mice infected with a neurovirulent strain of SV (NSV), had
      100% mortality, whereas NSV-infected scid mice developed persistent nonfatal
      infection. Inflammation was more intense in NSV-infected mice, however, no
      substantial differences in cytokine mRNA levels were detected when compared with
      mice with nonfatal SV infection suggesting that the cytokines measured do not in
      and of themselves lead to fatal central nervous system disease.

PMID- 8301133
TI  - Macrophage inflammatory protein-1 alpha and monocyte chemoattractant peptide-1
      elicit immediate and late cutaneous reactions and activate murine mast cells in
      vivo.
AB  - We have previously reported that monocyte chemoattractant protein-1 (MCP-1) is
      the most potent histamine-releasing factor (HRF) for basophils. Macrophage
      inflammatory protein-1 alpha (MIP-1 alpha) has modest histamine-releasing
      activity. The objective of this study was to investigate whether MCP-1 and MIP-1
      alpha would activate mast cells in vivo and induce a cutaneous inflammatory
      reaction in mice. To this goal, mouse hind footpads were separately injected with
      20 microliters of human recombinant MCP-1 or MIP-1 alpha (10(-7) M). Diluent was
      used as a control in the second footpad. The footpad-swelling response was
      measured at 30 min, 1 h, and then hourly for 6 h. Both MCP-1 (2.72 +/- 0.2 vs 2.1
      +/- 0.03 mm for diluent, n = 8, p < 0.02) and MIP-1 alpha (3.0 +/- 0.1 vs 2.1 +/-
      0.03 mm for diluent, n = 8, p < 0.02) induced an immediate swelling reaction. The
      immediate reaction was followed by a sustained late reaction that peaked within 1
      h and lasted for more than 6 h. Histologic examination of the footpads, obtained
      at hour 2, revealed that MCP-1 caused mild mononuclear cell infiltrates, moderate
      degranulation of mast cells, and soft tissue swelling. In contrast, MIP-1 alpha
      induced a severe inflammatory reaction that consisted of neutrophils, mononuclear
      cells, and degranulated mast cells. Electron microscope examination of the tissue
      revealed features of extensive mast cell degranulation by MIP-1 alpha and to a
      lesser extent by MCP-1. Thus, we conclude that mast cells are activated on
      injection of MCP-1, whereas degranulation of mast cells and recruitment of
      leukocytes contribute to the footpad reaction induced with MIP-1 alpha.

PMID- 8301134
TI  - The induction of persistence of I-A expression by macrophages from Bcgr mice
      occurs via a protein kinase C-dependent pathway.
AB  - We have described conditions by which MHC class II (I-A) glycoproteins can be
      induced to be differentially expressed after treatment of macrophages with rIFN
      gamma. Treatment of macrophages from BCG-resistant mice with 1 U of rIFN-gamma
      induced transient I-A expression that decayed in the presence of cycloheximide.
      Subsequent treatment of these macrophages with 100 U of rIFN-gamma induced the
      persistence of I-A that was not affected by cycloheximide. The aim of this
      investigation was to define, by pharmacologic intervention, the second signals
      that resulted in the induction of persistence of I-A. Treatment of the
      macrophages that transiently expressed I-A with PMA resulted in the induction of
      persistence. When we compared the effect of different protein kinase C (PKC)
      inhibitors with the induction of persistence by rIFN-gamma, we found that H-7
      blocked the induction of persistence only when added before or at the same time
      as the addition of a high dose of rIFN-gamma. In contrast, the addition of
      staurosporine to macrophages as late as 2 h after treatment with high doses of
      rIFN-gamma inhibited the induction of I-A persistence. The addition of a high
      dose of rIFN-gamma to macrophages previously treated with a low dose of rIFN
      gamma resulted in the synergistic activation of PKC. The effect of H-7 and of
      staurosporine on the activation of PKC activity coincided with the effect of
      these inhibitors on the induction of persistent I-A expression. Tyrosine kinase
      inhibitors genistein and herbimycin did not affect the induction of I-A
      persistence nor of PKC activation. Antibody to the IFN-gamma receptor inhibited
      PKC activation. Finally, the addition of the high dose of rIFN-gamma to
      macrophages from BALB/c.Bcgs mice, previously treated with the low dose of rIFN
      gamma, failed to activate high levels of PKC activity attained after similar
      treatment of macrophages from BALB/c.Bcgr mice. One effect of the Bcg gene may be
      to regulate the activation of PKC activity.

PMID- 8301135
TI  - Characteristics of a novel low affinity complement C3dg-binding protein of human
      platelets.
AB  - The breakdown products of the complement protein C3 function in receptor-mediated
      immune clearance. The catabolism of the C3 molecule, mediated by factors I and H,
      results in the generation of the fragments C3c and C3dg. C3dg binds to human
      platelets in a specific and saturable manner. The direct interaction of platelets
      with soluble C3dg may contribute to immune-mediated platelet destruction. More
      importantly, platelets may interact with opsonized pathogens or complement
      activating immune complexes via C3dg. In this report, we investigated the
      interaction of C3dg with platelets and calculated the Ka to be 3.2 x 10(6) M-1
      with 1100 to 2200 specific binding sites/platelet. In the presence of 5 mM
      calcium, both the Ka and the number of specific binding sites were modestly
      decreased to Ka = 2.8 x 10(6) M-1 with 1400 to 2400 specific binding
      sites/platelet. The Scatchard plots demonstrated a curvilinear character. On
      labeling C3dg with peroxidase and visualizing platelet-bound C3dg by electron
      microscopy, it was shown that binding sites for C3dg were restricted to the
      platelet plasma membrane. Using a cell attachment assay, platelet adhesion to
      C3dg was readily detectable; attachment to C3dg-coated plates was not blocked by
      fibrinogen or fibronectin. We have characterized the C3dg-binding protein of
      platelets using the chemical cross-linkers, SASD and DSS, to cross-link C3dg to
      thrombin-stimulated platelets. Gel filtration of the 125I-labeled C3dg-platelet
      complex revealed the presence of a large protein complex that was absent when
      125I-labeled C3dg alone was analyzed. SDS-PAGE of the radiolabeled cross-linked
      protein, followed by autoradiography, identified a 95-kDa membrane protein. The
      relationship of this C3dg-binding protein to other platelet membrane proteins has
      yet to be determined.

PMID- 8301136
TI  - Inhibition of TNF by a TNF receptor immunoadhesin. Comparison to an anti-TNF
      monoclonal antibody.
AB  - TNF is an important mediator of inflammation, which can have deleterious effects
      when produced inappropriately. We have described a recombinant inhibitor of TNF,
      termed TNFR-IgG, or TNFR immunoadhesin, composed of the extracellular portion of
      the type 1 (p55) TNF receptor (TNFR) linked to the hinge and Fc regions of IgG
      heavy chain. This bivalent, Ab-like molecule is a potent inhibitor of TNF,
      exhibiting significantly higher affinity for the cytokine than soluble TNFR.
      Here, we compare the TNF-neutralizing capacity of TNFR-IgG to that of an anti-TNF
      mAb. In vitro, TNFR-IgG was 10- to 50-fold more potent than anti-TNF mAb at
      blocking the cytotoxic effect of exogenous TNF on actinomycin D-treated murine L
      M cells. In vivo, the plasma half-life of TNFR-IgG in mice was approximately 6
      days, similar to that reported for the anti-TNF mAb. However, the immunoadhesin
      was approximately 10-fold more effective than the Ab at neutralizing the activity
      of endogenous TNF, as assessed in a model for murine listeriosis. These results
      demonstrate a markedly greater potency of the TNFR immunoadhesin compared with
      the anti-TNF mAb at inhibiting TNF activity in vitro and in vivo.

PMID- 8301137
TI  - Macrophage-colony-stimulating factor expression by anti-CD45 stimulated human
      monocytes is transcriptionally up-regulated by IL-1 beta and inhibited by IL-4
      and IL-10.
AB  - Macrophage (M)-CSF is a survival and differentiation factor for mononuclear
      phagocytes. Stimulation of human monocytes with immobilized mAb directed to CD45
      induces M-CSF message and small amounts of protein, which is strongly augmented
      by costimulation with IL-1 beta. This study was undertaken to study the
      mechanisms leading to the IL-1 beta-induced up-regulation of M-CSF production and
      to determine how the antiinflammatory cytokines, IL-4 and IL-10, affect M-CSF
      production in this system. We demonstrate that IL-1 beta enhanced M-CSF mRNA
      levels, in part, by increasing M-CSF gene transcription but had no effect on M
      CSF message half-life. The enhancement of M-CSF message levels in the presence of
      IL-1 beta was blocked by cycloheximide, suggesting that de novo protein synthesis
      was required. Moreover, soluble IL-1 receptors inhibited the effect of IL-1 beta
      on M-CSF production thus confirming that these effects were IL-1 receptor
      mediated. Both IL-4 and IL-10 strongly inhibited M-CSF secretion by anti-CD45/IL
      1 beta-induced monocytes that was accompanied by decreased M-CSF message levels.
      IL-4 and IL-10 repressed M-CSF gene transcription but did not affect M-CSF
      message half-life. These findings demonstrate that IL-1 beta, at least in part,
      transcriptionally up-regulates M-CSF production in anti-CD45-stimulated human
      monocytes, a process that can be negatively regulated by both IL-4 and IL-10.
      These results suggest that IL-1 beta, IL-4, and IL-10 control the survival and
      differentiation of human monocytes through a regulation of autocrine M-CSF
      production.

PMID- 8301138
TI  - Involvement of a botulinum toxin-sensitive 22-kDa G protein in stimulated
      exocytosis of human neutrophils.
AB  - Studies of human peripheral blood neutrophils (PMNs) demonstrated that botulinum
      neurotoxin D (BT-D) ADP-ribosylates a 22-kDa PMN G protein (G22k) and inhibits
      the exocytosis of both specific and azurophilic granules stimulated by FMLP.
      Furthermore, this inhibition of PMN exocytosis by BT-D was found to be correlated
      with the degree of irreversible ADP-ribosylation of G22k by BT-D and to require
      modification of at least 85% of PMN G22k before significant inhibition of
      secretion is observed. Although both pertussis toxin and BT-D inhibited
      exocytosis in FMLP-stimulated PMNs, the inhibitory effects of the two toxins were
      found to be additive. Pertussis toxin and BT-D also inhibited Ca2+/GTP/GTP gamma
      S-induced secretion in digitonin-permeabilized PMNs, but there were distinct
      differences between the inhibitory effects of the two toxins. In contrast to BT
      D, the exotoxin botulinum C3 was found to ADP-ribosylate primarily a 24- to 25
      kDa PMN protein, and it was not found to inhibit Ca(2+)- and GTP-induced
      secretion in permeabilized PMNs. Ultrastructural studies of BT-D-treated PMNs
      showed an accumulation of distinct membrane-bound organelles in the periphery of
      the cells after FMLP stimulation, suggestive of a toxin-induced block in
      organelle-plasma membrane fusion. Taken together, these findings indicate that BT
      D-sensitive G22k has a functional role in stimulated exocytosis of PMNs.

PMID- 8301139
TI  - Neutrophil elicitation in the reverse passive Arthus reaction. Complement
      dependent and -independent mast cell involvement.
AB  - Previous investigations in our laboratory have shown that mast cells play a
      significant role in the initiation of immune complex-mediated inflammation.
      Histamine, leukotrienes, and TNF released from mast cells are important mediators
      of early inflammatory processes. In the peritoneal reverse passive Arthus
      reaction, we observed a biphasic release of TNF. Mast cells were responsible for
      the first peak. The complement system is also known to be central to the
      expression of antibody-induced immune injury. Therefore, in this study, we
      investigated the significance of activated complement in regulating mast cell
      stimulation and neutrophil recruitment in the peritoneal reverse passive Arthus
      reaction. Mast cell degranulation and the release of TNF during the initiation of
      inflammation were blocked by decomplementation and C5 deficiency. Mast cell
      degranulation later in the reaction was complement-independent. Therefore, mast
      cells were activated in vivo in antibody-mediated injury by two different
      mechanisms, early in the reaction by complement and later by an unknown stimulus.
      Both mast cells and intact complement were also required for the full expression
      of neutrophil influx and release of TNF in the later phase. In fact, activated
      complement and mast cell mediators seemed to be the only factors necessary for
      the initiation of neutrophil recruitment. The findings significantly contribute
      to the understanding of the mechanisms involved in the induction of inflammatory
      processes in immune complex-mediated injury.

PMID- 8301140
TI  - Differential roles for triglyceride and phospholipid pools of arachidonic acid in
      human lung macrophages.
AB  - Arachidonic acid (AA) incorporation into and release from cellular glycerolipids
      are thought to be crucial events for the regulation of eicosanoid biosynthesis in
      inflammatory cells. The goal of our study was to determine the distribution of AA
      in the lipid pools of human lung macrophages (HLM) isolated from human lung
      parenchyma and to define the changes in AA pools occurring during cell
      activation. Mass spectrometry analysis indicated that the major pools of AA in
      HLM were located in phosphatidylethanolamine (PE), phosphatidylcholine (PC), and
      triglycerides (TG), and, to a lesser extent, in
      phosphatidylinositol/phosphatidylserine (PI/PS) and in a phospholipid similar to
      bis-(monoacylglyceryl)-phosphate (BMP). Exogenous AA was initially incorporated
      into TG and subsequently distributed within phospholipids. After 24 h of
      labeling, the distribution of exogenous AA in glycerolipid classes closely
      mimicked that of endogenous AA. Under these equilibrium conditions, HLM released
      18.7 and 20.2% of cellular AA when stimulated with TPA or A23187, respectively.
      Free AA was the major product released by TPA- or A23187-stimulated HLM. However,
      A23187 but not TPA also induced the formation of leukotriene B4 and 5-HETE. AA
      was released from PC > PI/PS > or = PE > BMP. In contrast to phospholipids, the
      amount of AA in TG increased 15 to 90 min after cell activation and returned to
      prestimulation levels after 180 min. These data indicate that AA is stored in
      several glycerolipid pools of HLM. Among these pools, BMP is unique of
      macrophages and TG are particularly enriched in AA in HLM. During the early stage
      of cell activation, phospholipids act as a source of AA, whereas TG function as a
      reacylation pool for AA released from phospholipids. These data indicate that TG
      and phospholipid pools have a differential role in the control of free AA levels
      generated during HLM activation.

PMID- 8301141
TI  - IFN and virus-inducible expression of an immediate early gene, crg-2/IP-10, and a
      delayed gene, I-A alpha in astrocytes and microglia.
AB  - IFN-gamma is a potent macrophage activator and induces a number of early and
      delayed genes. crg-2, the presumed murine homologue of human IP-10, belongs to a
      family of proinflammatory chemokines and is induced as an immediate early gene in
      response to IFN-gamma in macrophages. In contrast, class II MHC or Ia genes which
      are essential for Ag presentation are induced as a delayed response to IFN-gamma.
      We studied the expression of crg-2 and compared it with Ia in astrocytes and
      microglia of the central nervous system since, like macrophages, these cells can
      also produce a number of cytokines, express Ia molecules, and present Ag. We
      showed that crg-2 mRNA was induced in astrocytes and microglia by IFN-gamma as
      well as a paramyxovirus, Newcastle disease virus (NDV). Crg-2 protein was
      detected in the cytoplasm and in the supernatants of IFN-gamma-treated astrocytes
      and microglia. IFN-gamma and NDV or UV irradiated-NDV (UV-NDV) also induced Ia
      mRNA in these cells. The kinetics of expression of crg-2 and Ia mRNA were
      compared in the same systems. While crg-2 mRNA appeared within 2 h and reached a
      maximum in 6 to 8 h, Ia mRNA was not detected before 8 h. Cycloheximide
      superinduced crg-2 mRNA induced by IFN-gamma or UV-NDV but it abolished Ia mRNA
      induction by the same stimuli. The induction of crg-2 in astrocytes and microglia
      likely contributes to the development of immune-mediated inflammation in response
      to viruses or in autoimmune diseases of the central nervous system.

PMID- 8301142
TI  - Retinoic acid inhibition of IL-1-induced IL-6 production by human lung
      fibroblasts.
AB  - IL-6 is a multi-functional cytokine that plays an important role in normal
      biologic homeostasis and disease pathogenesis. Retinoids are vitamin A analogs
      that regulate the function of a wide variety of inflammatory and structural
      cells. To further understand the biology of retinoids and IL-6 we determined
      whether all-trans-retinoic acid (RA) and other retinoids regulate lung fibroblast
      IL-6 production. RA did not stimulate fibroblast IL-6 production. Instead, it
      inhibited the production of IL-6 by IL-1-stimulated cells. This effect was dose
      dependent with an IC50 of 10(-7) M RA and significant inhibition being noted with
      doses of RA as low as 10(-8) M. These inhibitory effects could not be explained
      by cytotoxicity or a shift in the kinetics of IL-6 production. They also did not
      appear to involve alterations in the early events in IL-1-induced IL-6
      production, because RA inhibited IL-6 production even when added 6 h after IL-1
      and RA did not inhibit IL-1 binding to cell surface IL-1 receptors. RA inhibition
      of IL-6 protein production was associated with a comparable decrease in IL-6 mRNA
      accumulation and gene transcription. 13-cis-retinoic acid, retinol,
      retinaldehyde, all-trans etretin, Ro 13-6298, and 9-cis retinoic acid also
      inhibited IL-1-induced IL-6 production. However, 4-hydroxyphenyl retinamide and
      etretinate did not share this property. The inhibitory effects of these analogues
      may be mediated by nuclear retinoic acid receptors as mRNA encoding RAR-alpha,
      RAR-gamma, and RXR-alpha were present, and RAR-beta was induced by RA in human
      lung fibroblasts. These studies demonstrate that RA and other retinoid analogs
      inhibit IL-1-induced IL-6 production and that this effect is analog-specific and,
      at least partially, transcriptionally mediated.

PMID- 8301144
TI  - Molecular analysis of IgA deficiency. Evidence for impaired switching to IgA.
AB  - The most common form of primary immunodeficiency is IgA deficiency (IgAD).
      However, the molecular basis of this disease remains elusive. Therefore, to
      address this issue we made a systematic analysis of the molecular events leading
      to IgA production. B lymphocytes that produce IgA have undergone somatic
      rearrangement that joins the switch (S) mu to S alpha region with deletion of the
      intervening sequences. Examination of the resulting S mu/S alpha junctions in
      unstimulated PBMC from IgAD patients by nested primer PCR revealed a significant
      decrease in the number of the S mu/S alpha fragments. To obtain the antisense
      primers to generate the S mu/S alpha fragments, we sequenced the human S alpha 1
      and the downstream region extending to the C alpha 1 locus. Similar to previously
      reported switch sequences, we also found the S alpha 1 to be predominantly
      composed of pentameric repeats GAGCT and GGGCT. The decrease in the number of S
      mu/S alpha fragments is consistent with a profound decrease in the C alpha
      membrane mRNA expression in unstimulated PBMC, as well as in the C alpha mRNA
      levels and IgA production in PWM-stimulated PBMC. Sequence analysis of the switch
      junctions from IgA-producing cell lines, control donors, and an IgAD patient
      showed direct joining in 8 of 9 cases examined. TGF-beta 1, previously shown to
      be the switch factor for human and mouse IgA, was also examined. No difference in
      the TGF-beta 1 mRNA levels in unstimulated PBMC between the control subjects and
      the IgAD patients were detected. Our findings indicate that the failure to switch
      to IgA-producing B lymphocytes, or an impaired survival of such cells, may be an
      important molecular mechanism in IgAD.

PMID- 8301145
TI  - B cells process and present lupus autoantigens that initiate autoimmune T cell
      responses.
AB  - Antibodies against U small nuclear ribonucleoprotein (snRNP) particles are a
      common finding in the sera of humans with SLE and in certain strains of mice with
      murine lupus. It is likely that Th cells are important in amplifying this
      autoantibody response. The focus of this work was to investigate events that
      might initiate autoimmune B and T cell response in non-autoimmune mice to native
      snRNP particles. Mice that were immunized and boosted with native mouse snRNPs
      failed to produce any detectable specific anti-snRNP antibody or T cell
      responses, suggesting that these autoreactive cells were deleted from the
      repertoire or were anergic to stimulation with this self Ag. In contrast,
      immunization with native foreign (human) snRNPs elicited both T cells and cross
      reactive anti-snRNP antibodies; the latter predominantly were directed toward the
      A protein of the U1 snRNP. When mice were immunized with human and mouse snRNPs
      together in adjuvant, T cells specific for mouse snRNPs could be elicited. The
      results of these experiments suggested that the mechanism of breaking T cell
      tolerance to self snRNPs was dependent on the ability of cross-reactive B cells
      to process and present these autoantigens. To address this hypothesis, B cells
      purified from mice immunized with recombinant human A protein were transferred
      into naive mice. Upon boosting with native mouse snRNPs, autoreactive CD4+ T
      cells specific for mouse Ags, and not cross-reactive with human snRNPs, were
      observed. These studies support a model of molecular mimicry whereby autoantigen
      presenting B cells are generated by foreign cross-reactive determinants that can,
      in turn, elicit an autoimmune T cell response.

PMID- 8301143
TI  - VH and V kappa segment structure of anti-insulin IgG autoantibodies in patients
      with insulin-dependent diabetes mellitus. Evidence for somatic selection.
AB  - In some patients with insulin-dependent (type I) diabetes mellitus (IDDM),
      autoantibodies to insulin are present at diagnosis. After initiation of the
      treatment with not only animal but also human insulin, anti-insulin, mainly IgG,
      autoantibodies become a major component of the autoimmune response in virtually
      all IDDM patients. Their structure, however, is still relatively unknown. We
      analyzed the structure of the VH and V kappa segments of three human IgG mAb
      derived from three IDDM patients. The sequences of VH genes of two IgG, mAb13 and
      mAb48, were 98.3 and 96.6% identical with those of the H11 and 1.9III genes
      (VHIII family), respectively. The sequence of the VH gene of the third IgG,
      mAb49, was 98.6% identical with that of the 51p1 gene (VHI family). All three IgG
      mAb used V kappa III segments. The V kappa III gene sequences of mAb13 and mAb49
      were 97.9 and 98.9% identical, respectively, to that of the kv3g gene; the mAb48
      V kappa gene sequence was 96.5% identical to that of the kv328 gene. The VH
      and/or V kappa segments of these anti-insulin IgG mAb are similar to Ig V genes
      expressed in the fetal, and adult normal and autoimmune B cell repertoires. The
      nucleotide differences displayed by the three anti-insulin IgG mAb VH gene
      sequences, when compared with those of the closest reported germ-line genes, were
      concentrated in the CDR (6.2 x 10(-2) and 0.8 x 10(-2) difference/base in CDR and
      FR, respectively; p < 0.01, chi 2 test), and yielded a significantly higher
      putative replacement (R) to silent (S) mutation ratio in the CDR (12.0) than in
      the framework (0.2). The concentration of nucleotide differences in the CDR and
      their high R:S putative mutation ratios were consistent with the hypothesis that
      these expressed VH genes underwent a process of somatic mutation and Ag-driven
      clonal selection. That such differences constituted somatic point-mutations was
      formally proved in IgG mAb13, by differentially targeted PCR amplification and
      Southern blot hybridization of the mAb13-producing cell line DNA. The putative
      germ-line gene that gave rise to the expressed VH segment was cloned using
      genomic DNA from PMN of the same patient whose B cells were used for the
      generation of this mAb. Overall, in the anti-insulin IgG mAb VH and V kappa III
      genes, the (putative and verified) somatic point-mutations yielded 27 amino acid
      replacements, of which 14 nonconserved. Four of these resulted in positively
      charged residues, three Arg and one His.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8301146
TI  - T cell receptor alpha-chain repertoire of pathogenic autoantibody-inducing T
      cells in lupus mice.
AB  - The production of pathogenic anti-DNA autoantibodies in mice with lupus nephritis
      is dependent on special autoimmune Th cells that can also transfer the disease
      into preautoimmune mice. In previous work, these pathogenic Th cells were cloned
      and their TCR beta-chains were sequenced to reveal a recurrent motif of anionic
      residues in their CDR3 loops. Accordingly, approximately half of the Th clones
      were found to be specific for nucleosomal Ag that contain cationic residues.
      Herein, we analyzed the TCR alpha-chain repertoire of 15 of these pathogenic Th
      clones and found them to be heterogeneous, even among the nucleosome-specific Th
      clones. Most of these autoimmune TCR alpha-chains contained anionic residues in
      their CDR3 in addition to cationic residues. Therefore, these pathogenic Th
      clones of lupus probably recognize epitopes with mixed charge runs that are
      derived from autoantigens, such as histone-DNA complexes. Interestingly, the V
      alpha gene segments used by 10 of these Th clones derived from the (SWR x NZB)F1
      lupus mice differed from previously reported sequences indicating that they were
      new members or alleles of the respective V alpha gene family. One of the Th
      clones used a gene from an entirely new murine V alpha gene family, identified
      here as V alpha 23, which consisted of approximately two members that were
      conserved among strains with different V alpha haplotypes. Knowledge of the
      primary structure of the TCR expressed by these pathogenic Th clones of lupus
      would help in the analysis of their antigenic specificities and also would be
      essential for studying their regulation in transgenic mice carrying these
      autoimmune TCR genes.

PMID- 8301147
TI  - Variable regions of Ig heavy chain genes encoding antithyrotropin receptor
      antibodies of patients with Graves' disease.
AB  - We have established EBV-transformed human B cell clones producing monoclonal
      antithyrotropin receptor antibodies from two patients with Graves' disease. We
      then isolated and characterized Ig H chain genes of 5 B cell clones with the
      thyrotropin-binding inhibitor Ig (TBII) activity and 4 B cell clones with the
      thyroid-stimulating antibody (TSAb) activity. We found that VH gene families used
      in the 5 TBII clones were all VH-III, although those of the four TSAb clones were
      diverse, including VH-II, -III, -IV, all -V. Most of VH segments used in TBII and
      TSAb are commonly used in other autoantibodies and fetal liver repertoire. The
      frequency of somatic mutations in TBII was higher than that in TSAb. Inasmuch as
      the same germline VH segment (V3-23) was used for both TBII and TSAb, the
      frequency and position of somatic mutations may be important for generation of
      TBII and TSAb.

PMID- 8301148
TI  - Cardiac antigen-specific autoantibody production is associated with
      cardiomyopathy in Trypanosoma cruzi-infected mice.
AB  - An inflammatory cardiomyopathy may develop in humans and experimental animals
      with chronic Trypanosoma cruzi infection (Chagas' disease). Among the possible
      mechanisms involved in the pathogenesis of Chagas' cardiomyopathy, induction of
      heart-specific autoimmune responses has recently received substantial
      experimental support. The goal of the current study was to determine whether
      cardiac Ag-specific antibodies are produced in T. cruzi-infected mice with heart
      disease and, if so, to determine their Ag specificities. Upon infection with the
      Brazil strain of T. cruzi, C57BL/6 mice develop a cardiomyopathy that is
      histologically similar to that observed in chronically infected humans. Antisera
      from these mice were found to react with three cardiac Ag, having relative
      molecular masses of 200, 150, and 53 kDa. p200 and p150 are specifically found in
      heart muscle, although p53 is found in skeletal muscle as well. C57BL/6 mice
      infected with the Guayas strain of T. cruzi, which do not develop cardiomyopathy,
      did not produce antibodies to p200, p150, or p53, indicating that these
      antibodies may be specific markers of cardiomyopathy. Finally, p200 and p53 were
      identified as the contractile protein myosin and the intermediate filament
      protein desmin, respectively. This last finding is of special interest, because
      antibodies specific for myosin or desmin have been detected in humans and
      experimental animals with other natural and experimental cardiomyopathies. This
      suggests that infection with particular strains of T. cruzi may lead to the
      development of a cardiac Ag-specific autoimmune disease, possibly involving one
      or more of the Ag identified in this study.

PMID- 8301149
TI  - Up-regulation of the MHC class II molecules on B cells by peptide ligands.
AB  - MHC class I and class II molecules present peptide Ag to T lymphocytes. Peptides
      are critical in class I heavy chain folding and/or stable association with beta
      2m. A recent study suggests the role of peptide Ag binding for MHC class II alpha
      and beta-chain heterodimers to enter into a compact state and allow their
      transport to the cell surface. We have investigated the effect of peptide ligands
      on the expression of MHC class II I-A(d) molecules on the B cell hybridoma, TA3.
      These cells, when cultured in vitro, gradually lost the surface expression of I
      A(d) molecules. Incubation with peptides, having high affinity for binding to
      intact I-A(d) molecules, significantly increased the surface expression of I-A(d)
      in less than 24 h. The ability of peptides to induce increased expression of I
      A(d) correlated with the affinity of peptide to intact I-A(d), and an I-Ak
      restricted peptide did not have an effect on I-A(d) expression. The effect could
      be reversed after the removal of the peptide Ag. Based on our studies with
      inhibitors of protein synthesis and intracellular transport, the mechanism for up
      regulation of I-A(d) expression by peptides seems to involve intracellular
      pathway but appears not to require new protein synthesis or transport from ER.
      Our results suggest that the decrease in surface expression of I-A(d) on TA3
      cells may result from their failure to generate or to be saturated with naturally
      processed peptide ligands. Thus peptide ligands are evidently important in
      regulating surface expression of MHC class II molecules and their recognition by
      T lymphocytes.

PMID- 8301150
TI  - Relationship between multiple biologic effects of rapamycin and the inhibition of
      pp70S6 protein kinase activity. Analysis in mutant clones of a T cell lymphoma.
AB  - Rapamycin (RAP) inhibits several biologic responses in the YAC-1 T cell lymphoma,
      including the serum-driven proliferation and cyclin A mRNA expression, the
      induction of Ly-6E Ag expression by IFN, and the induction of IFN-gamma
      production by IL-1. RAP also suppresses the enzymatic activity of the 70 kDa S6
      protein kinase (pp70s6k). To define the mechanistic relationship between these
      multiple effects of RAP, we have generated stable somatic mutants with altered
      sensitivities to this drug. A first series of mutants, represented by the R19,
      4R16, and 10R13 clones, showed markedly reduced sensitivity to the inhibitory
      effect of RAP on all biologic responses tested and on pp70s6k activity. Two other
      mutant types, R103 and R125, were both highly sensitive to RAP-mediated
      suppression of proliferation, of IL-1-induced IFN-gamma production, and of
      pp70s6k activity but differed in their Ly-6E response. This response was not
      affected by RAP in the R125 clone and was enhanced in the R103 clone. Therefore,
      the inhibitory effects of RAP on proliferation and IL-1-mediated IFN-gamma
      induction both appear associated with the inhibition of pp70s6k activity, whereas
      the modulation of Ly-6E induction is independent from the latter. Moreover, the
      cellular binding of [3H]dihydro-FK-506 was found to be blocked by RAP in all
      mutant types to the same extent as in wild-type YAC-1 cells, suggesting that the
      altered sensitivity to the effects of RAP in these mutants is not due to an
      inability of the drug to enter the cells or to interact with FKBP. Further
      biochemical characterization of the mutant cells described here is expected to
      help clarify the mechanisms of RAP action.

PMID- 8301151
TI  - Cloning and structural analysis of four genes encoding interferon-omega in
      rabbit.
AB  - By using an ovine interferon-tau (IFN-tau) cDNA probe, four recombinant phages
      were isolated from a rabbit genomic library and sequenced from nucleotides -450
      to 1,300 relative to the CAP site. Each of the four rabbit genes contains an open
      reading frame of 595 nucleotides and code for proteins that exhibit structural
      characteristics of the interferon-omega (IFN-omega) family. They display more
      than 98% identity in their coding regions. The deduced amino acid sequences share
      > 96% sequence similarity. In contrast, the 5' and 3' noncoding regions have
      diverged considerably (approximately 50% identity). Amino acid comparisons of
      rabbit IFN-omega with IFN-omega of other species reveal the highest degree of
      identity with human (72%), followed by porcine (68%) IFN-omega. Rabbit IFN-omega
      displays only 57% sequence similarity with ovine IFN-tau. The coding regions of
      the four genes subcloned in a cytomegalovirus eukaryotic expression vector and
      transfected in monkey COS-7 cells direct the production of proteins that protect
      bovine and rabbit cells against vesicular stomatitis virus infection, thus
      demonstrating that these genes encode fully active IFN proteins. The expression
      of these genes was studied in Sendai-induced rabbit leukocytes. A single band of
      poly(A)+RNA hybridized with a rabbit IFN-omega probe under stringent conditions,
      whereas no IFN-omega transcript was detected with RNA isolated from uninduced
      leukocytes. Southern blot analysis suggest the existence of at least eight IFN
      omega genes or pseudogenes in the rabbit genome.

PMID- 8301152
TI  - Transcription termination/polyadenylation occurs at multiple sites in the human
      type I interferon receptor gene.
AB  - Based on the previously reported sequence, we isolated an independent cDNA clone
      encoding a binding component of the human type I interferon receptor (IFN-R).
      This cDNA is identical to the published sequence except that it lacks 62 bases of
      5' untranslated sequence and terminates at the first of two potential
      polyadenylation sites. In Northern blot analyses of poly(A)+RNAs from both IFN
      sensitive and IFN-resistant Daudi cells, this cloned cDNA hybridized to a
      predominant mRNA of 2.4 kb, as well as to mRNAs of 1.8, 4.8, and 5.6 kb, and
      occasionally 6.9 kb. These various transcripts, which were also observed at
      similar levels in Raji B cells and two T-cell lines, Jurkat and MOLT-4, were
      detected after high-stringency washes, and by alternate probes corresponding to
      subfragments of the cDNA. In contrast, only the 4.8- and 5.6-kb transcripts
      hybridized to a polymerase chain reaction (PCR)-derived probe that corresponded
      to genomic sequences immediately down-stream from the second polyadenylation
      site. These results indicate that the latter transcripts arise from the same gene
      as the predominant 2.4-kb mRNA due to incomplete transcription termination at
      either of the known polyadenylation sites. Finally, Northern blot analysis of
      total RNAs revealed the presence of the predominant 2.4-kb type I IFN-R
      transcript in numerous tissues from second trimester human fetuses, suggesting
      that the type I IFN-R gene is constitutively expressed in multiple cell types.

PMID- 8301153
TI  - Systemic recombinant human interferon-beta treatment of relapsing-remitting
      multiple sclerosis: pilot study analysis and six-year follow-up.
AB  - A pilot study was undertaken to test the safety and establish the side effect
      profile of recombinant human interferon-beta 1b (Betaseron, Berlex Laboratories,
      Richmond, CA), in patients with relapsing-remitting multiple sclerosis (RRMS).
      During the initial dose finding period (24 weeks), five groups of 6 patients each
      were treated by subcutaneous injection three times each week with either 0.8, 4,
      8, or 16 million units (mU) of Betaseron or placebo (WHO Standard). Although some
      side effects were noted in all groups, a dose-related trend in reduction of
      exacerbation frequency and side-effect profile was noted. Patients given 16 mU
      had no exacerbations during the initial dosing period, but associated side
      effects led to dose reduction or dropout. An 8 mU dose was selected for further
      study after 24 weeks, and continuous dosing at 8 mU in 15 patients has now
      exceeded 6 years. Side effects abated over time. Neutralizing antibody developed
      in most patients, but titers were variable, fluctuated independently of clinical
      course, and tended to fall with prolonged treatment. A dose-dependent rise in
      neopterin levels was observed during the initial dosing period. This pilot study
      has demonstrated responsiveness to Betaseron, shown a stable safety profile over
      time, and established guidelines for a dosing regimen to evaluate and optimize
      further the efficacy of Betaseron in RRMS.

PMID- 8301154
TI  - Consensus interferon induces peak mRNA accumulation at lower concentrations than
      interferon-alpha 2a.
AB  - The biological activity of a novel recombinant interferon, r-metIFN-con1, which
      represents a consensus sequence of the most commonly appearing amino acids at
      each locus of 14 naturally occurring IFN-alpha s, was assessed and compared to
      that of IFN-alpha 2a. The increase in cellular mRNA levels for three IFN
      inducible genes served as a quantitative measure of the effectiveness of the
      stimulation by each of the IFNs. Three cell lines were treated with equimolar
      amounts of two IFNs encompassing a 5 log range and mRNA was extracted at five
      different times after treatment. In all cases, r-metIFN-con1 produced mRNA
      increases at lower concentrations than IFN-alpha 2a. HLA-DR alpha mRNA, which is
      not affected by IFN-alpha in ME180 or Daudi cells, was also not affected by r
      metIFN-con1. However, in Eskol cells, both IFNs effected an increase in HLA-DR
      alpha mRNA to similar levels. The r-metIFN-con1 was effective at approximately 10
      fold lower molar concentrations. At effective concentrations (10-fold lower molar
      dose of r-metIFN-con1), both IFNs produced similar kinetics of accumulation of
      all three mRNAs tested. r-metIFN-con1 is therefore more effective than IFN-alpha
      2a at the level of mRNA regulation as well as the antiviral and antiproliferative
      activities that have been reported previously.

PMID- 8301155
TI  - Effects of cytokines on the pituitary-adrenal axis in cancer patients.
AB  - Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor
      necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and
      inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate
      glucocorticoid secretion. In this study, the effects of variable doses and
      repetitive administration of IFNs and TNF on secretion of pituitary hormones and
      cortisol were measured. Patients were given for a period of 15 days on
      alternating days injections of IFN-beta (IFN-beta ser), 90 or 450 x 10(6) IU, IFN
      gamma, 0.1-100 x 10(6) IU, or TNF 125-275 micrograms/m2. Sixty to 120 min after
      IFN-beta ser injection median levels of cortisol, adrenocorticotropin (ACTH),
      prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol
      excretion increased significantly during the day following IFN-beta ser
      administration. IFN-gamma > or = 30 x 10(6) IU caused a comparable rise in plasma
      cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact
      that increased cortisol secretion was associated with a rise in the level of ACTH
      as well as PRL and GH suggests that the cytokines increased cortisol by
      stimulating the anterior pituitary. The hormonal response induced by cytokines
      was unrelated to their pyrogenic effect, undiminished with repetitive treatment,
      and not dose-dependent above a threshold level. These observations reinforce the
      concept of a physiologic link between the immune system and the hypothalamic
      pituitary-adrenal (HPA) axis.

PMID- 8301156
TI  - The effect of interferon-gamma on rejection and neutrophil function following
      transplantation.
AB  - Rats were used as a model for a living heterotopic cardiac allograft organ
      transplant. Rats treated in this model with recombinant rat interferon-gamma (IFN
      gamma) showed accelerated rejection in a dose-dependent fashion. However, rats
      treated with maintenance doses of cyclosporine and IFN-gamma expressed increased
      rejection at 20 days that had resolved completely by 45 days post
      transplantation. Polymorphonuclear leukocytes (neutrophils) were isolated from
      the blood of rats, and their function was determined by treating the cells with f
      Met-Leu-Phe (fMLP) and measuring superoxide produced. Results indicate that the
      neutrophils from rats treated with maintenance doses of cyclosporine and IFN
      gamma still had increased IFN-gamma-modulated fMLP-induced respiratory burst and
      that maintenance cyclosporine therapy can inhibit the IFN-gamma-mediated
      accelerated rejection without compromising the antimicrobial effects of IFN-gamma
      treatment.

PMID- 8301157
TI  - Interference by a non-interferon-inducing subvariant of benign
      encephalomyocarditis virus-B with the ability of EMCV-D to produce insulin
      dependent diabetes mellitus in ICR Swiss male mice.
AB  - The D variant of encephalomyocarditis virus (EMCV-D) produces a disease syndrome
      that mimics insulin-dependent diabetes mellitus (IDDM) in certain mouse strains.
      Benign EMCV-B interferes with the ability of EMCV-D to produce IDDM. Because EMCV
      B induces the production of relatively large amounts of interferon (IFN), it has
      been hypothesized that the interference by EMCV-B with the pathogenesis of EMCV-D
      is due to IFN. However, we have previously reported that in outbred ICR Swiss and
      inbred BALB/cByJ mice, interference by EMCV-B with the development of IDDM in
      response to infection with EMCV-D does not appear to involve IFN. We have
      isolated a subvariant of EMCV-B (EMCV-B1) which, preliminary experiments
      indicate, does not induce the production of detectable levels of IFN in cell
      culture. Studies were initiated using this subvariant to determine more
      conclusively if IFN is involved in interference by EMCV-B with the pathogenesis
      of EMCV-D. The data in the present study show that EMCV-B1 does not induce the
      production of detectable levels of IFN either in cell culture or in mice, but
      retains other reported characteristics of the parent EMCV-B, including the
      ability to interfere with the production of IDDM by EMCV-D in ICR Swiss male
      mice. These observations strengthen the hypothesis that protection of pancreatic
      beta cells in ICR Swiss mice by EMCV-B occurs by a mechanism other than IFN.

PMID- 8301158
TI  - Partial phenotypic reversion of HeLa cells by long-term interferon-alpha
      treatment.
AB  - Human papillomaviruses (HPV) are associated with malignant cervical neoplasia.
      Several HPV-related diseases have been shown to be sensitive to interferon (IFN)
      treatment. HeLa cells contain and express the HPV type 18 genome and were used as
      a model for the evaluation of the viral expression regulation and the effect on
      the malignant phenotype during IFN treatment. Cells were treated continuously
      with 200 IU/ml IFN-alpha 2b or natural leukocyte INF-alpha for six passages (42
      days). Some IFN-induced changes were observed: decrease of HPV-18 mRNA
      expression, changes of cell morphology, and reduction of clonogenicity in soft
      agar. Tumorigenicity in nude mice was not modified. Other targets of the IFN
      system were analyzed, and an increase of the 2',5'-oligoadenylate synthetase mRNA
      level and a down-regulation of type I IFN receptor were found. These results
      demonstrate that long-term IFN-alpha treatment induces a partial phenotypic
      reversion of HeLa cells to a more differentiated stage were down-regulation of
      HPV-18 expression could play a central role. It therefore confirms that the IFN
      alpha treatment may be therapeutically useful in cervix cancer produced by HPV
      18.

PMID- 8301159
TI  - Interferon-resistant Daudi cells are deficient in interferon-alpha-induced ISGF3
      alpha activation, but remain sensitive to the interferon-alpha-induced increase
      in ISGF3 gamma content.
AB  - Low levels of the transcription factor ISGF3 alpha were detected in the cytoplasm
      and nucleus of untreated Daudi cells, which increased markedly following
      interferon (IFN) treatment. In contrast no ISGF3 alpha was detected in an IFN
      resistant clone of Daudi cells, DIF8, and only low levels were detected in these
      cells after IFN-alpha treatment. High levels of ISGF3 were produced in vitro,
      however, by the addition of ISGF3 alpha to extracts of IFN-treated DIF8 cells,
      indicating that IFN is unable to produce substantial amounts of functional ISGF3
      alpha in DIF8 cells. A second clone of IFN-resistant Daudi cells, DIF3, also
      exhibited defective ISGF3 alpha production, which was restored to normal in the
      subclone DIF3REV5 that had reverted to high IFN sensitivity. Thus, the
      antiproliferative effect of IFN on Daudi cells and derived clones is closely
      related to the level of ISGF3 present in the nucleus of these cells. IFN-alpha,
      however, also enhances the content of ISGF3 gamma in IFN-resistant cells as well
      as certain proteins of unknown function, raising the possibility that a second
      pathway of IFN-alpha signal transduction, distinct from the ISGF3 pathway,
      remains functional in both DIF8 and DIF3 cells.

PMID- 8301160
TI  - Smoking habits and attitudes of Irish dentists and dental students.
AB  - Objective To ascertain firstly the proportions of smokers and ex-smokers among
      Irish dentists and dental students, secondly their knowledge of the role of
      tobacco in the aetiology of oral cancer and thirdly the attitudes of dentists to
      matters of public health policy relating to tobacco. Background Smoking has been
      associated with various diseases including oral cancer and other oral disease.
      Dentists are known to be potentially effective health educators and their role in
      smoking cessation is now appreciated. Study Design A questionnaire was
      distributed to dental students and a longer questionnaire to dentists; results
      were examined statistically. Results 14% of dentists were smokers and 45% were ex
      smokers; 20% of students were smokers and 15% were ex-smokers. Most smokers
      declared an intention of ceasing. Almost all dentists were aware of links between
      smoking and oral cancer. There was strong support from dentists for higher taxes
      on tobacco and stricter control of advertising and sponsorship. Conclusions Irish
      dentists and dental students are less likely to smoke than the general public.
      Dentists are aware of major risk factors in oral cancer and support government
      intervention to reduce smoking prevalence. Such views should assist public health
      planners.

PMID- 8301161
TI  - Updates in dental materials--Part 2: Resin cements.
AB  - Recent years have seen a number of innovations and developments with respect to
      dental materials and their applications in clinical dentistry. This series of
      short articles considers the more important aspects of these developments under
      the general term 'Updates in Dental Materials'. Dental composite systems and
      bonding to tooth material were discussed in Part I. Resin cements are treated in
      this article. Part 3 presents dental amalgams and Part 4 deals with advances in
      ceramic materials.

PMID- 8301162
TI  - The extent and scope of the Membership in General Dental Surgery Examination in
      the Royal College of Surgeons in Ireland.

PMID- 8301163
TI  - Some modifications to the step-back technique in root canal preparation.

PMID- 8301164
TI  - The stability of bimaxillary osteotomy after correction of skeletal Class II
      malocclusion.
AB  - This study investigates changes following bimaxillary osteotomy for correction of
      Class II malocclusion. The records of 15 patients who had simultaneous maxillary
      impaction and sagittal split ramus osteotomy with rigid fixation are evaluated.
      Traditional cephalometric analysis as well as finite element and Euclidean
      distance matrix analyses are used to assess the changes. The maxilla was
      relatively more stable than the mandible; the maxilla stayed within 1 mm of its
      immediate postoperative position, whereas the mandible was 2 mm from the achieved
      surgical changes. The mandible rotated in a clockwise direction during the first
      6 months after surgery. The mandibular plane angle increased by 2.9 degrees. This
      is, in part, believed to be due to posterior condylar displacement during
      surgery. Theories of mandibular relapse following sagittal split advancement
      osteotomy are discussed. The new methods of morphometric analysis do not require
      the superimposition of cephalograms and are able to separate maxillary from
      mandibular changes.

PMID- 8301165
TI  - Cephalometric measures as indicators of facial attractiveness.
AB  - Orthodontic treatment is frequently undertaken to improve facial appearance.
      However, the contribution of the components of malocclusion to perceptions of
      attractiveness is not clear. This study uses three panels of judges-
      undergraduates, dental students, and orthodontic residents--to quantify the
      associations between common objective measures of dental and skeletal
      anteroposterior disproportion and subjective perceptions of facial
      attractiveness. Consistent and similar correlations between anteroposterior
      measures and facial attractiveness rankings are shown for all three panels, with
      overjet being most strongly associated with rankings of attractiveness.

PMID- 8301166
TI  - ANB skeletal types correlated to facial morphology: Euclidean distance matrix
      analysis.
AB  - Pretreatment lateral skull radiographs of 145 patients aged 7 to 20 years are
      classified according to an ANB-angle reading corrected for the position of the
      maxilla and rotation of the jaw. The Euclidean distance matrix analysis is
      applied to compare the overall facial morphology between Classes I and II. This
      method differentiates between size and shape and localizes those areas that
      differ the most. Statistically significant different facial morphologies were
      demonstrated in the 32 patients aged 15 years or more. The younger patients with
      skeletal Classes I and II did not possess these different morphological
      characteristics. The results show that standard cephalometric classification
      criteria do not always correlate to actual differences in the overall facial
      morphology.

PMID- 8301167
TI  - Significance of the contour of the lateral surface of the maxilla for planning
      osteotomy lines in orthognathic surgery.
AB  - The Le Fort I osteotomy is one of the most frequently used procedures in
      orthognathic surgery. The preoperative planning of a Le Fort I osteotomy usually
      involves a two-dimensional lateral radiograph. On the lateral radiograph, the
      movement of the maxilla in the sagittal and vertical planes can be simulated, and
      the position of the osteotomy line in relation to the occlusion can be
      determined. However, the lateral radiograph consists of two dimensions, whereas,
      during surgery, three dimensions have to be considered. The contour of the
      lateral surface of the maxilla and its individual regional variations are not
      reflected on the lateral radiograph. Therefore, this third dimension's influence
      on treatment planning is investigated. Discrepancies of the position of planned
      osteotomy cuts are described after the transfer from two to three dimensions.
      Discrepancies of the positions of reference points and lines are up to 3.3 mm.
      Therefore, it is not possible to transfer reference points and reference lines
      from the lateral radiograph to the maxilla nor to move the mobilized maxilla
      along the planned osteotomy lines in a precise manner. It is possible to indicate
      the general direction of the osteotomy lines. Results of this study show the
      necessity for the precise control of three-dimensional positioning of the maxilla
      during treatment planning, cast surgery, and actual surgery.

PMID- 8301168
TI  - Tantalum implants as markers for evaluating postoperative orthognathic surgical
      changes.
AB  - The stability of sagittal split osteotomy advancements is not always 100%
      predictable. Assessment of postsurgical changes has historically relied on
      clinical evaluation of dental changes and superimposition of serial cephalograms,
      both of which have been shown to have serious drawbacks. A technique that
      improves the analysis of postsurgical changes is described in this paper;
      tantalum pin implants are placed in the osteotomized segments of patients
      undergoing surgical advancements. Implants eliminate many of the problems
      (orthodontic, growth, and remodeling changes) related to superimposition of
      presurgical and postsurgical cephalograms. Using this technique, surgical changes
      can be precisely analyzed, and the contribution of each factor of postsurgical
      relapse can be determined. This information, concerning the magnitude and
      direction of postsurgical changes, aids in following an individual's progress and
      increases the accuracy of large group studies by eliminating sources of
      variability in radiographic and clinical interpretation.

PMID- 8301169
TI  - Evaluation of emergency screws in nonstripped pilot holes in bone.
AB  - Clinicians continue to search for a rigid internal fixation system that will
      remain stable in thin bone, such as that found in the lateral walls of the
      maxilla. Insertion of a large-diameter screw in a pilot hole has been suggested
      to improve screw retention. This study evaluates insertional and stripping torque
      of six emergency screw systems placed in nonstripped pilot holes of porcine rib
      (thickness < or = 2 mm). The Timesh and Synthes emergency screws did not properly
      fit into the nonstripped pilot holes. The Techmedica emergency screw was the most
      retentive. The Luhr, Wurzburg, and Steinhouser emergency screws were less
      retentive. The Techmedica emergency screw had the greatest stripping torque in
      nonstripped pilot holes, but it was not significantly greater when compared to
      the stripping torque of identical screws placed in 2.0-mm stripped holes. The
      Luhr, Wurzburg, and Steinhouser emergency screws placed in 1.5-mm pilot holes had
      significantly less stripping torque when compared to identical screws placed in
      2.0-mm stripped holes. It appears the Luhr, Wurzberg, and Steinhouser 2.0-mm self
      tapping screws have a greater stripping torque than the corresponding emergency
      screw when placed in 1.5-mm pilot holes.

PMID- 8301170
TI  - Disseminated intravascular coagulation following orthognathic surgery.
AB  - When performing any type of surgery, the surgeon must be cognizant of hidden
      bleeding. In the case presented, Le Fort I osteotomy is performed to correct a
      disharmonious maxillomandibular relationship of a 19-year-old man with diabetes
      insipidus. Postoperatively, excessive bleeding is seen at the surgical site, IV
      catheter insertion area, and rectum. It was later determined that the blood
      originated from the oral structure and traveled through the stomach and rectum.
      Examination of the blood revealed disseminated intravascular coagulation.

PMID- 8301171
TI  - The use of 5-fluorouracil in glaucoma filtration surgery.
AB  - Failure of glaucoma filtration surgery usually results from scarring at the
      surgical site. Studies have shown that fibroblast proliferation plays an
      important role in scar formation which results in a mechanical barrier to
      filtration (Gressel, Parris, & Folberg, 1984). Fibroblasts are immature collagen
      producing cells which proliferate at the site of chronic inflammation. The
      antimetabolite 5-fluorouracil (5-FU) can inhibit fibroblast activity. Over the
      past ten years, the adjunctive use of 5-FU in filtration surgery has met with
      increased success and is particularly indicated in those patients at greatest
      risk of filtration failure.

PMID- 8301172
TI  - The role of the health educator.
AB  - This article describes the role of health education and the health educator. The
      development of this field is explored from the point of view of government
      involvement, insurance requirements, and the Patient Self-Determination Act. The
      ever increasing importance of the health educator in hospitals is discussed along
      with preferred methods of patient education. Specific roles within an ophthalmic
      setting are described and include the educator's work with both a "well" and a
      "sick" population.

PMID- 8301173
TI  - Planning for high risk ophthalmic ambulatory patients.
AB  - Ophthalmic ambulatory care settings are faced with providing expert care for a
      high volume of individuals with increasingly complex nursing and psychosocial
      needs. These needs may include financial assistance, medications, transportation,
      shelter, home healthcare, and various community resources. A case study will
      demonstrate the effectiveness of interdisciplinary collaboration between nursing
      and social services in identifying high risk ophthalmic patients, coordinating
      resources, and decreasing fragmentation of care.

PMID- 8301174
TI  - Ophthalmic nursing in Saudi Arabia: a western expatriate's perspective.
AB  - The purpose of this first article in a series "Ophthalmic nursing in Saudi
      Arabia: A western expatriate's perspective" is to acquaint readers with Saudi
      Arabia and the King Khaled Eye Specialist Hospital in Riyadh. In subsequent
      articles, the various challenges which face both the expatriate nursing staff and
      the local Saudi nurses in this setting will be addressed. The King Khaled Eye
      Specialist Hospital presents an unique and challenging ophthalmic nursing
      experience for the expatriate with an adventurous spirit!

PMID- 8301175
TI  - Ophthalmic nursing research--the last frontier.
AB  - It is the consensus of nursing leaders that the utilization of research in
      clinical practice is paramount if nursing is to be perceived as creditable by
      other professionals and by health consumers. However, ophthalmic nurses also face
      a second challenge because of the dearth of research addressing the outcomes of
      ophthalmic nursing behaviors.

PMID- 8301176
TI  - Ocular emergencies.

PMID- 8301177
TI  - Patient vs. client--should it be a quandary?

PMID- 8301178
TI  - Reproducibility and variation of corneal thickness in different locations in the
      cornea as measured by an ultrasonic pachymeter.
AB  - Corneal thickness was measured in nine positions of nineteen normal eyes with an
      ultrasonic pachymeter. A standardized protocol was used to examine for
      intraobserver and interobserver variation, day to day variation, and time of day
      variation in the measurement of corneal thickness. No statistically significant
      difference was noted for most points in intraobserver, interobserver, day to day,
      or different time of day variation measurements. However, it was noted that
      central measurements of corneal thickness tended to be less variable (more
      reproducible) than paracentral (p = .0366) and peripheral (.0032) measurements.
      Paracentral measurements were less variable than peripheral measurements (p =
      .0323). While this was a small study, 95% confidence intervals were also
      calculated for each of the nine corneal positions where measurements were
      performed.

PMID- 8301179
TI  - Education and training programs for expatriate and Saudi nurses at KKESH.
AB  - The purpose of this second article in a series of "Ophthalmic nursing in Saudi
      Arabia: A western expatriate's perspective" is to acquaint readers with the
      education and training programs for the expatriate nursing staff and Saudi nurses
      at the King Khaled Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia.

PMID- 8301180
TI  - President's message: new directions in healthcare.

PMID- 8301181
TI  - Patient responses to topical anesthesia for cataract surgery.
AB  - This presentation will summarize subjective comments and clinical findings
      obtained from 27 cataract patients who underwent extracapsular cataract
      extraction by phacoemulsification and intraocular lens implantation under topical
      anesthesia 0.5% tetracaine hydrochloride (HCl) without retrobulbar block. All
      data presented in this study was obtained by one ophthalmic registered nurse who
      questioned the patient in the immediate preoperative period, observed all
      operative procedures, questioned each patient immediately postoperatively and
      performed a slit lamp examination and interview with each patient on the first
      post-operative day. As a result of this study, specific nursing interventions
      have been altered and unique circumstances identified that reinforce the valuable
      contributions of the ophthalmic registered nurse in the completion of successful
      cataract surgery.

PMID- 8301182
TI  - Views on the future of nursing.

PMID- 8301183
TI  - Aging and the visual system.
AB  - The ocular aging process involves everyone. Misconceptions about visual changes
      from aging versus visual changes from a disease have resulted in needless vision
      loss for many in the older population. Lack of understanding and misinformation
      may cause a delay in seeking medical attention for diagnosis and treatment.

PMID- 8301184
TI  - Assessment and education of the diabetic with vision loss.
AB  - An educational program is essential for patients whose diabetes is complicated by
      significant visual loss. Nurses have a unique opportunity to assess the patient's
      learning needs and to provide pertinent educational experiences for the patient.
      A check off educational assessment tool can provide a quick survey of patient
      teaching and discharge needs. A patient teaching record can be utilized to
      document when and what is taught as well as patient response. A teaching packet
      can be designed that contains the purpose, teaching objectives, methods of
      teaching, and available resources for the patient. Appropriate tools will
      encourage staff involvement in patient teaching and documentation by making the
      process easier.

PMID- 8301185
TI  - Nurse educators--a link to community ophthalmic care.
AB  - Ophthalmic nurses can do much in providing community education to various groups
      of people. A background in patient education and broad knowledge of ophthalmology
      allows nurses to be ideally suited for community education. This interaction can
      benefit both the community and the nursing profession. Nurses can use their
      abilities to interact outside of a traditional setting and to provide valuable
      ophthalmic information to the public.

PMID- 8301186
TI  - Alternative patient care delivery systems: a combined ophthalmic nursing unit and
      a cost effective ophthalmic surgery program.
AB  - To be competitive as a tertiary facility in today's healthcare environment, our
      institute implemented two nursing programs using the Continuous Quality
      Improvement (CQI) framework: a) creation of the Nursing and Trauma Center, a
      nursing unit with the flexibility to adjust to continuing changes in patient mix
      comprising three nursing units (eye emergency room, same day surgery unit, and
      inpatient unit) designed to consolidate and standardize care to ophthalmic
      patients and develop a multi-skilled nursing staff to provide nursing care to all
      ophthalmic patient populations; and b) creation of the Controlled Medical
      Intensity (CMI) program, in which certain ophthalmic surgeries are performed in
      the most cost effective and efficient manner (while maintaining quality care).
      Conceived to compete with surgi-centers, CMI surgery is performed under local
      retrobulbar anesthesia with minimal, one-time intravenous (IV) conscious sedation
      (administered by operating room/recovery room nurses according to a standard
      protocol). Surgical supplies are standardized. These expanded roles have given
      nurses the opportunity to practice professional autonomy using nursing judgment.

PMID- 8301187
TI  - Nine point corneal thickness measurements and keratometry readings in normal
      corneas using ultrasound pachymetry.
AB  - Central, paracentral, and peripheral corneal thickness measurements using
      ultrasound pachymetry and keratometry readings were performed in 303 normal
      corneas. The mean central corneal thickness was 515 +/- 34 microns (standard
      deviation) ranging from 410 to 625 microns. Mean paracentral thickness
      measurements ranged from 522 +/- 40 microns inferiorly to 574 +/- 41 microns
      superiorly; mean peripheral thickness measurements ranged from 633 +/- 50 microns
      inferiorly to 673 +/- 49 microns superiorly. Central corneal thickness
      measurements were not found to be correlated with age, however, paracentral and
      peripheral thickness measurements tended to become thinner with age. There was
      also a trend that central corneal thickness decreased as the average keratometry
      reading increased. These trends, however, were not statistically significant. The
      mean difference between right and left central corneal thicknesses was 25
      microns, ranging from zero to 136 microns. No significant differences in corneal
      thickness or keratometry readings were found between males and females or right
      and left eyes. No differences in these measurements were found with regard to
      time of day, month of the year, or systemic medication use. We conclude that
      there is a wide range of corneal thickness centrally, paracentrally, and
      peripherally in normal corneas.

PMID- 8301189
TI  - Vision screening for infants and preschool children.
AB  - Eye examinations and vision screening at the recommended ages are preventive
      health measures that can yield immense benefits in preventing visual loss.
      Educational programs can be designed to provide parents and healthcare workers
      about children's eye screening and referral procedures.

PMID- 8301188
TI  - The cultural challenges of educating Saudi ophthalmic patients at KKESH.
AB  - The purpose of this final article in a three-part series "Ophthalmic nursing in
      Saudi Arabia: A western expatriate's perspective" is to acquaint readers with
      some of the cultural challenges confronting the expatriate nursing staff when
      educating Saudi ophthalmic patients at the King Khaled Eye Specialist Hospital
      (KKESH) in Riyadh, Saudi Arabia. The foreign nurse is able to plan and provide
      patient education that is culturally compatible, by possessing an increased
      awareness and understanding of the diversity in Saudi culture and how it
      influences their healthcare beliefs.

PMID- 8301190
TI  - Author--are you or aren't you?

PMID- 8301191
TI  - Writer's tips.

PMID- 8301192
TI  - The National Organization for Albinism and Hypopigmentation (NOAH)

PMID- 8301193
TI  - The immunopathology of chemotactic cytokines: the role of interleukin-8 and
      monocyte chemoattractant protein-1.

PMID- 8301194
TI  - The calcium paradox is most likely limited to muscle tissue.

PMID- 8301195
TI  - The immune response to Histoplasma capsulatum: unearthing its secrets.

PMID- 8301196
TI  - Ascitic fluid albumin and water flows in patients with alcoholic cirrhosis:
      effects of peritoneovenous shunting.
AB  - Ascites labeled albumin and water kinetics were studied at steady state by
      intercompartmental clearances in cirrhotic patients whose ascites volumes ranged
      from 6.4 to 25.2 L. In 20 patients mean (+/- SD) ascitic fluid albumin clearance
      (equivalent to lymphatic absorption) was 3.5 +/- 1.9 L/day. In seven of them,
      lymphatic absorption was 3.4 +/- 0.8 L/day, total water absorption from ascitic
      fluid (outflow equals inflow at steady state) was 125.8 +/- 21.5 L/day. Vascular
      capillary water absorption (total minus lymphatic) was 122.4 +/- 21.4 L per 24
      hours. Lymphatic absorption was less than 4% of total but accounted for all
      albumin absorbed (13.2 +/- 6.2 gm/day). Maximum lymphatic absorption was less
      than 10 L per 24 hours; peritoneovenous shunting augmented this function. Mean
      inflow water albumin concentration was 0.11 +/- 0.06 gm/L. If plasma albumin were
      diluted to concentration in ascites, calculated water inflow required would be
      2.82 L/day. Actual inflow was 47 times that required. The major volume outflow
      path was through peritoneal venous capillaries; water and small-radius solute
      absorption through this route increased inflow water albumin concentration to
      ascites level. Concurrently, whole ascitic fluid was absorbed without sieving
      through lymphatics. Observed ascites albumin concentration in subjects with
      advanced cirrhosis was produced by water absorption from a large volume of dilute
      solution rather than dilution of a small inflow volume, in which albumin
      concentration originally was hyperoncotic to ascitic fluid. Large-volume
      transperitoneal water diversion from sources in high-pressure, extrahepatic
      splanchnic capillaries to absorption through parietal nonportal, low-pressure,
      peritoneal venous capillaries would significantly reduce portal plasma flow into
      liver and have deleterious systemic hemodynamic consequences.

PMID- 8301198
TI  - High-density lipoprotein inhibits the production of platelet activating factor
      acetylhydrolase by HepG2 cells.
AB  - We previously demonstrated that HepG2 cells secrete platelet activating factor
      (PAF) acetylhydrolase, which is identical to human plasma PAF acetylhydrolase.
      PAF acetylhydrolase has been shown to be associated with high-density
      lipoproteins (HDLs) and low-density lipoproteins (LDLs) in plasma, and
      lipoprotein environment affects the enzyme activity. We examined the effects of
      HDL and LDL on the production of PAF acetylhydrolase by HepG2 cells. These
      lipoproteins were treated with diisopropylfluorophosphate (DFP) to inhibit
      completely the endogenous PAF acetylhydrolase. PAF acetylhydrolase activity in
      the control medium conditioned for 24 hours was 37 +/- 2.6 pmol/mg cell
      protein/min (mean +/- SD, n = 3). DFP-treated HDL markedly inhibited the
      production of PAF acetylhydrolase by HepG2 cells in a concentration-dependent
      manner, and 100 micrograms/ml of HDL inhibited the production by 82%. DFP-treated
      LDL had a slight inhibitory effect. Sulfur 35-labeled methionine-labeled PAF
      acetylhydrolase had a molecular weight of about 43 kd. In the presence of 100
      micrograms/ml DFP-treated HDL, the labeling of PAF acetylhydrolase was decreased
      both in conditioned medium and in cell homogenate (to 62% and 42% of control
      values, respectively). DFP-treated HDL did not affect PAF acetylhydrolase
      activity of conditioned medium when they were mixed immediately before the assay.
      However, when conditioned medium was incubated for 24 hours with HDL, PAF
      acetylhydrolase activity was inhibited to 78% of the control value. Analysis with
      gel filtration chromatography disclosed that incubation with HDL resulted in the
      transfer of the LDL-associated enzyme to HDL fraction.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8301197
TI  - Sodium retention does not occur at a critical threshold of liver function in
      alcoholic cirrhosis.
AB  - Sodium retention is triggered in rats with experimental liver injury at a
      critical threshold of liver function. We compared liver function and sodium
      retention in serially studied patients with alcoholic cirrhosis to determine
      whether a similar threshold exists in human beings. Antipyrine, caffeine, and
      cholic acid clearance were measured in 35 men with alcoholic liver disease.
      Nineteen patients were evaluated on two or more occasions; between studies, 28
      remained in sodium balance (group NN), six spontaneously developed sodium
      retention and ascites formation (group NY), and seven spontaneously lost ascites
      (group YN). A threshold between patients with and without sodium retention did
      not exist for any of the clearance measurements. Indeed, values overlapped widely
      between the two groups. Antipyrine and cholate clearance were significantly
      reduced in patients with sodium retention, but caffeine clearance was similar in
      the two groups. Antipyrine and caffeine clearance declined significantly between
      the first and second study in group NY; cholate clearance did not change. No
      significant differences were observed between studies in group YN. In several
      patients of this group, liver function worsened as ascites spontaneously
      resolved. Impaired liver function commonly but not invariably accompanies sodium
      retention in patients with cirrhosis. A threshold at which sodium retention
      occurs or resolves does not exist.

PMID- 8301199
TI  - Administration of gamma interferon in human subjects decreases plasminogen
      activation and fibrinolysis without influencing C1 inhibitor.
AB  - Recombinant gamma interferon (rHuIFN-gamma) has been recognized to increase mRNA
      and protein levels of C1 inhibitor (C1 INH) in various human cells. Further, when
      administered to patients with colon cancer, it increased plasma C1 INH levels. A
      prospective trial was initiated to determine whether rHuIFN-gamma could elevate
      plasma C1 INH levels in six normal volunteers and two patients with type I
      angioedema. After 1 month of observation of plasma C1 INH levels, rHuIFN-gamma
      was administered subcutaneously at 25 micrograms/M2 daily for 4 consecutive days.
      All healthy volunteers and patients experienced local erythema, headache,
      myalgias, and chills during the administration of rHuIFN-gamma. C1 INH,
      prekallikrein, high-molecular-weight kininogen, and factor XII levels in plasma
      were not influenced by the rHuIFN-gamma administration. One patient with
      hereditary angioedema (HAE) had an attack of angioedema 3 days after completion
      of rHuIFN-gamma therapy. During the attack, circulating cleaved high-molecular
      weight kininogen, kallikrein-alpha 2-macroglobulin complexes, and an altered 50
      kd form of kallikrein were detected in the patient's plasma. Additional studies
      showed that rHuIFN-gamma treatment resulted in decreased total fibrinolytic
      activity. It was found that immediately after rHuIFN-gamma treatment, tissue
      plasminogen activator activity and antigen levels were not significantly
      decreased in volunteers. Plasminogen activator inhibitor levels rose
      significantly, but this activity was not due to plasminogen activator inhibitor-1
      antigen, whose value significantly fell. These data suggest that rHuIFN-gamma may
      stimulate the expression of another plasminogen activator inhibitor.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301200
TI  - Comparison of antibody activity against various microorganisms in intravenous
      immunoglobulin preparations determined by ELISA and opsonic assay.
AB  - In the present study the level of antimicrobial antibodies and the phagocytosis
      promoting activity in immunoglobulin preparations produced for intravenous use
      were assessed. The level of antibodies directed against various microorganisms in
      six immunoglobulin preparations was determined by using an enzyme-linked
      immunosorbent assay (ELISA) and was shown to be either equal to or higher than
      that of pooled normal human serum. All preparations were able to promote
      phagocytosis of Staphylococcus aureus, Escherichia coli K12, and Streptococcus
      pyogenes by human granulocytes. Substantial differences among the various
      preparations in antibody activity were noted. In particular, Intraglobulin,
      chemically modified by beta-propiolactone treatment, exhibited little activity in
      both the ELISA and the phagocytosis assay. In contrast, IVIG SRC, Gamimmune,
      Sandoglobulin (treated at low pH in presence or absence of trace amounts of
      pepsin), and Gammagard (treated by ion-exchange chromatography) showed good
      activity in both assays. Comparison of the results of the ELISA and phagocytosis
      assay for the various preparations indicated a good correlation except for S.
      aureus with a moderate (strain 42D) or high (strain Cowan I) protein A content.
      These data indicate that the antibody activity of immunoglobulin preparations
      against various microorganisms determined by ELISA can be used to predict their
      opsonic activity.

PMID- 8301201
TI  - Neutrophil-specific antigen NB1 inhibits neutrophil-endothelial cell
      interactions.
AB  - Neutrophil-specific antigen NB1 is located on a 58 to 64 kd glycosyl
      phosphatidylinositol-linked plasma membrane glycoprotein. NB1 antigen can be
      detected on neutrophils from 97% of healthy volunteers, and NB1 antigen is
      expressed on subpopulations of neutrophils. Neutrophil subpopulations with
      varying functions have been described, and we hypothesize that NB1 antigen may
      play an important role in neutrophil function. We compared the function of NB1
      positive and NB1-negative neutrophils obtained from several persons. There were
      no differences in the adhesion of NB1-positive and NB1-negative neutrophils
      incubated in C5a, N-formyl-Met-Leu-Phe (FMLP), phorbol myristate acetate (PMA),
      or buffer to type IV collagen, fibronectin, laminin, or polystyrene. However, the
      adherence to human umbilical vein endothelial cells (HUVEC) monolayers of
      unstimulated NB1-positive neutrophils was less than to NB1-negative neutrophils
      (20.0% +/- 4.2% vs 31.7% +/- 5.8%; p < 0.01). When neutrophils were stimulated
      with C5a, PMA, or FMLP, no differences were found in the adhesion of NB1-positive
      and NB1-negative cells to the same surfaces. When NB1-positive neutrophils were
      incubated with rabbit polyclonal anti-NB1 Fab fragments, their adherence to HUVEC
      was increased (32.9% +/- 10.1% vs 18.3% +/- 5.0%; p < 0.05). Fab fragments
      prepared from normal rabbit serum had no effect on neutrophil adherence to HUVEC.
      The chemotaxis of NB1-positive neutrophils to FMLP through nitrocellulose was
      significantly greater than that of NB1-negative neutrophils (p = 0.03), but there
      was no difference in chemotaxis to FMLP through polycarbonate membranes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301202
TI  - Triflavin, an antiplatelet peptide, inhibits tumor cell-extracellular matrix
      adhesion through an arginine-glycine-aspartic acid-dependent mechanism.
AB  - The interaction of tumor cells with extracellular matrix components such as
      laminin, fibronectin, and collagen has been shown to be mediated through a family
      of cell-surface receptors that specifically recognize an arginine-glycine
      aspartic acid amino acid sequence within each protein. Triflavin, a 7.5 kDa
      cysteine-rich polypeptide purified from Trimeresurus flavoviridis snake venom,
      belongs to a family of arginine-glycine-aspartic acid-containing peptides termed
      disintegrins that have been isolated from the venoms of various vipers and shown
      to be potent inhibitors of platelet aggregation. In this study, we showed that
      triflavin inhibited adhesion of human hepatoma J-5 cells to extracellular
      matrices (fibronectin, vitronectin, fibrinogen, and collagen type I) in a dose
      dependent manner. On the other hand, triflavin exerted a limited inhibitory
      effect on cell attachment to collagen type IV and laminin (< or = 40%). Triflavin
      is approximately 1000 times more potent than glycine-arginine-glycine-aspartic
      acid-serine at inhibiting cell adhesion. When immobilized on plate, triflavin
      promoted J-5 cell attachment; this attachment was inhibited by glycine-arginine
      glycine-aspartic acid-serine. In addition, triflavin labeled with iodine 125
      binds to J-5 cells in a saturable manner and its binding was also inhibited by
      glycine-arginine-glycine-aspartic acid-serine. Its Kd value was estimated to be
      3.9 x 10(-7) mol/L and the number of binding sites was around 60,000 per cell.
      Furthermore, triflavin did not affect tritiated thymidine uptake during a 3-day
      incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301203
TI  - The turnover of 57Co-labeled cyanocobalamin bound to cobalamin binding proteins
      in patients with chronic myelogenous leukemia.
AB  - Individual plasma specimens from six patients with chronic myelogenous leukemia
      (CML) in chronic phase were incubated with [57Co]cyanocobalamin and injected into
      patients to study the turnover of cobalamin bound to haptocorrin and
      transcobalamin. The [57Co] radioactivity bound to haptocorrin and transcobalamin
      was determined after separating the proteins by adsorption to insolubilized
      antibodies to haptocorrin. The distribution of the radioactivity on the different
      forms of cobalamin and on haptocorrin isoproteins were determined. The fractional
      catabolic rate of hapatocorrin (0.102 to 0.158 d-1) and transcobalamin (3 to 29 d
      1) was of the same magnitude as previously reported for a reference population.
      During the first 24 hours of the turnover, no change of the cyanocobalamin form
      was registered, indicating that conversion of cyanocobalamin to the coenzyme
      forms of cobalamin does not take place in the circulation. The haptocorrin
      isoprotein pattern changes in alkaline direction during the first 5 hours
      indicated that the glycoprotein was desialinated during circulation. From the
      calculated turnover parameter, the possible competition between transcobalamin
      and haptocorrin for the transport of cobalamins in CML is estimated to be of
      minor clinical significance. In conclusion, the increased plasma concentration of
      haptocorrin in CML is due to an increased liberation of haptocorrin and is not
      due to a decreased turnover of the protein.

PMID- 8301204
TI  - Evidence for Pneumocystis carinii binding to a cell-free substrate: role of the
      adhesive protein fibronectin.
AB  - Attachment of Pneumocystis carinii organisms to the alveolar epithelium is
      probably a prerequisite for the initiation of P. carinii infection. Previous
      studies have demonstrated a role for the extracellular matrix protein fibronectin
      in mediating attachment of P. carinii organisms to cultured alveolar cells;
      however, these studies could not clearly distinguish the role of fibronectin
      binding to P. carinii organisms and fibronectin binding to the alveolar cells.
      The current study demonstrates the direct binding of P. carinii organisms to
      substrate-bound soluble fibronectin P. carinii organisms bound specifically in a
      concentration-dependent manner to fibronectin-coated plates; maximum binding
      (19.1% +/- 1.9%) occurred at a fibronectin concentration of 50 micrograms/ml. P.
      carinii organisms did not bind significantly to bovine serum albumin-coated
      plates (5.8% +/- 1.2%). Binding of P. carinii organisms to fibronectin-coated
      plates was inhibited in a concentration-dependent manner by addition of the
      tetrapeptide arginine-glycine-aspartic acid-serine, which represents the active
      site of the fibronectin cell-binding domain. Similarly, attachment of P. carinii
      organisms was significantly inhibited by the addition of monoclonal antibodies
      directed against the cell-binding domain of fibronectin or by the addition of
      calcium ion chelators. To evaluate the role of the major P. carinii surface
      antigen gp120 in attachment of P. carinii organisms, purified gp120 and specific
      polyclonal anti-gp120 antibodies were used to inhibit attachment of P. carinii
      organisms to fibronectin-coated plates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301205
TI  - Gamma interferon stimulates monocyte chemotactic protein (MCP-1) in human
      mesangial cells.
AB  - Cell-mediated immunity and monocyte infiltration is a prominent histologic
      feature of several different types of glomerulonephritis. Monocyte influx to the
      glomerulus correlates with glomerular hypercellularity and proteinuria.
      Glomerular mesangial cells, in addition to being targets for inflammatory
      stimuli, are also effector cells that actively participate in glomerular
      pathology. Mesangial cells release monocyte chemotactic protein (MCP-1). In the
      present article, we characterized and studied the regulation of MCP-1 released by
      cultured human mesangial cells. Serum-deprived mesangial cells constitutively
      release chemotactic activity that is neutralized by specific anti-MCP-1 antibody.
      An antibody to baboon MCP-1 recognized 16, 15, and 11 kd proteins from
      concentrated conditioned medium that were consistent with the presence of
      different forms of MCP-1. Gamma interferon (IFN-gamma), tumor necrosis factor
      alpha (TNF-alpha), and interleukin-1 (IL-1) markedly stimulate the release of MCP
      1 as measured by a specific and sensitive radioimmunoassay. The release of MCP-1
      in response to these cytokines is at least partially dependent on de novo
      synthesis of the protein because all three cytokines markedly stimulate the
      expression of MCP-1 mRNA. These data demonstrate that human mesangial cells
      synthesize and release at least three different forms of MCP-1 and that IFN-gamma
      and other cytokines regulate the secretion of MCP-1. IFN-gamma and MCP-1 may play
      a major role in the recruitment and activation of monocytes to the inflamed
      glomerulus.

PMID- 8301206
TI  - Phlebotomy of 500 or 750 milliliters of whole blood followed by isovolemic
      hemodilution or autologous transfusion yields similar hemodynamic, hematologic,
      and biochemical effects.
AB  - The purpose of this study was to evaluate the effects of phlebotomy of 500 or 750
      ml of whole blood followed by isovolemic hemodilution or autologous transfusion
      on hemodynamic, hematologic, and biochemical parameters in healthy subjects. Four
      groups of normovolemic male subjects (n = 6 or 7 per group), aged 18 to 41 years,
      participated in this 10-day study at Upjohn Research Clinics, Kalamazoo, Mich. On
      day 1 two groups had phlebotomy of 500 ml; of these, one group underwent
      immediate postphlebotomy autologous transfusion (group 1) and the other underwent
      immediate postphlebotomy isovolemic hemodilution and then autologous transfusion
      on day 3 (group 2). Two other groups had 750 ml phlebotomy, also on day 1; of
      these, one group underwent immediate postphlebotomy autologous transfusion (group
      3) and one underwent immediate postphlebotomy isovolemic hemodilution followed by
      autologous transfusion on day 3 (group 4). Noninvasive measurement of vital
      signs, blood pressure, and cardiac function; oximetry; and select hematologic and
      biochemical parameters were made. On day 1 in groups 2 and 4 transient reductions
      in hematocrit, hemoglobin, red blood cell count, fibrinogen, and albumin were
      seen concurrent with prolongation of coagulation studies. Erythropoietin was
      increased severalfold on day 3 (groups 2 and 4, p < 0.001). The physiologic
      response to phlebotomy of 500 or 750 ml was similar and was well tolerated in
      normal subjects.

PMID- 8301207
TI  - Effect of diaspirin cross-linked hemoglobin and norepinephrine on systemic
      hemodynamics and regional circulation in rats.
AB  - Diaspirin cross-linked hemoglobin (DCLHb) (400 mg/kg, i.v.) produced a pressor
      effect that was equal to that produced by norepinephrine (NE) (25
      micrograms/kg/min i.v. infusion). Total peripheral resistance was increased by
      DCLHb and more significantly by NE. Heart rate was not affected by DCLHb but was
      significantly increased by NE. The cardiac output and stroke volume were
      insignificantly increased by DCLHb but were significantly decreased by NE. DCLHb
      and NE produced a significant increase in blood flow to the heart. The vascular
      resistance in the heart was not affected by DCLHb but was decreased by NE. DCLHb
      did not affect the renal and brain circulation, but NE in kidneys decreased the
      blood flow and increased the vascular resistance, whereas in the brain it
      increased the blood flow and decreased the vascular resistance. DCLHb increased
      the blood flow to the stomach and small intestine. The vascular resistance was
      not affected by DCLHb in the gastrointestinal tract. NE did not affect the blood
      circulation in the gastrointestinal tract. Blood flow to the spleen was increased
      by DCLHb, and there was no change in the vascular resistance. NE insignificantly
      decreased the blood flow to the spleen and significantly increased the vascular
      resistance. The blood circulation to the mesentery and pancreas was not affected
      by DCLHb, whereas NE increased the blood flow without affecting the vascular
      resistance. DCLHb produced a significant increase in the blood flow to the skin
      without affecting the vascular resistance, whereas NE did not affect the blood
      flow but increased the vascular resistance. DCLHb did not affect the blood flow
      to the musculo-skeletal system but increased the vascular resistance, whereas NE
      decreased the blood flow and increased the vascular resistance. In summary,
      although the pressor effect of DCLHb and NE at the doses studied is equal, DCLHb
      did not decrease the blood flow to any organ, whereas NE produced significant
      decreases in blood flow to several organs. It is concluded that the blood flow to
      most of the organs is either increased or not affected by DCLHb.

PMID- 8301208
TI  - Effects of endotoxin injury on endothelial cell adenosine metabolism.
AB  - Adenosine is a potent autocoid that acts as a vasodilator and modulator of
      inflammatory responses. Endothelial cells possess several mechanisms for altering
      circulating levels of adenosine and are capable of release of adenosine
      metabolites. We used cultured bovine aortic and main pulmonary arterial
      endothelial cells to determine whether endotoxin can alter adenosine uptake or
      release of adenosine metabolites. We found that 24 hours, but not 6 hours, of
      incubation with endotoxin caused endothelial cell injury, as assessed by cell
      detachment and chromium 51 release. Despite this injury the extent of
      [3H]adenosine uptake was unchanged. Using thin-layer chromatography to identify
      adenosine and its metabolites, we found that [3H]adenosine was primarily
      metabolized into intracellular hypoxanthine and adenine nucleotides. After 1, 6,
      and 24 hours of incubation with endotoxin there was an increase in extracellular
      adenosine metabolites, which was accompanied by decreases in the level of
      intracellular adenosine 5'-triphosphate. The appearance of adenosine metabolites
      in culture supernatants was a more sensitive measure of endothelial cell injury
      than 51Cr release or adherent cell number. The extracellular purine metabolite
      observed in response to endotoxin injury was mainly hypoxanthine. Our findings
      suggest that hypoxanthine release is an early event in endotoxin-induced
      endothelial cell injury. Because hypoxanthine may act as a substrate for xanthine
      oxidase, resulting in toxic oxidant production, its release has the potential of
      exacerbating vascular injury caused by endotoxin.

PMID- 8301209
TI  - Functional characterization of interstitial macrophages and subpopulations of
      alveolar macrophages from rat lung.
AB  - The specific function of interstitial macrophages (IM) in the lung is poorly
      understood because of difficulties in isolating these cells in high purity or
      large number. In the present studies, a pure population of enzymatically isolated
      IM and lung macrophages obtained mechanically from the lung were compared
      functionally with alveolar macrophages recovered by lavage (AM). Macrophages
      isolated mechanically from the tissue and AM displayed similarly high levels of
      Fc-receptor mediated phagocytosis. In contrast, IM phagocytized significantly
      fewer opsonized sheep red blood cells per macrophage than AM. In addition,
      although some variations in the amounts of nitric oxide and superoxide anion
      produced by AM and macrophages obtained by mechanical tissue disruption were
      observed, these subpopulations released significantly more of these mediators
      than IM. These data support the concept that macrophages isolated by mechanical
      disruption of the tissue represent a subpopulation of AM. We also found that, in
      contrast to AM, IM did not respond synergistically to combinations of IFN-gamma
      and lipopolysaccharide (LPS) or tumor necrosis factor alpha in terms of nitric
      oxide production. Furthermore, regulation of superoxide anion release in AM and
      IM by LPS and/or IFN-gamma was distinct. Taken together, these studies
      demonstrate that IM are functionally different from other macrophage
      subpopulations which might reflect their unique location within the lung.

PMID- 8301210
TI  - A single assay for measuring the rates of phagocytosis and bacterial killing by
      neutrophils.
AB  - We have developed a method that enables the rates of phagocytosis and killing of
      bacteria by neutrophils to be measured in a single assay. Neutrophils were
      incubated with bacteria, and at specific intervals were separated from uningested
      bacteria by low speed centrifugation. Rates of phagocytosis and killing were
      calculated from the decrease in number of extracellular bacteria and change in
      the number of intracellular bacteria. Both phagocytosis and killing were shown to
      follow first-order kinetics, and rate constants were calculated without having to
      separate the assay into two phases. In contrast to two-step methods, our method
      measures killing from the moment the neutrophils start ingesting the bacteria,
      and also eliminates the need to halt neutrophil activity temporarily and restart
      the assay after the extracellular bacteria have been removed. We obtained
      reproducible results for the phagocytosis and killing of Staphylococcus aureus
      (t1/2 = 9 min and 6 min respectively) and Escherichia coli (t1/2 = 10 min and 2
      min respectively). We also were able to detect a 56% impairment in the rate of
      killing of S. aureus by neutrophils from an individual with a low level of
      myeloperoxidase.

PMID- 8301211
TI  - Flow cytometric analysis of the cytotoxic effects of Actinobacillus
      actinomycetemcomitans leukotoxin on human natural killer cells.
AB  - The goal of this investigation was to determine if human natural killer (NK)
      cells were susceptible to the cytolytic effects of the Actinobacillus
      actinomycetemcomitans leukotoxin (LTX). Following treatment with LTX (0-200
      ng/ml), NK cell activation by interleukin-2 (IL-2) was evaluated. LTX inhibited
      the IL-2-induced expression of both CD69 and the IL-2 receptor. Furthermore, the
      up-regulation of CD56 was also impaired. To determine whether the observed
      functional deficits were the result of cell death, NK cell viability was
      evaluated by flow cytometry. Changes in forward and side light scatter patterns
      consistent with cell death were observed within 60 min. Direct analysis of cell
      viability by measuring propidium iodide exclusion, however, indicated little
      change in the viability of LTX-treated NK cells. Electron microscopic analysis of
      NK cells exposed to LTX revealed early nuclear alterations characterized by
      hyperchromaticity, nuclear fragmentation, and condensation of nucleoplasm.
      However, no change in membrane integrity was initially noted. Finally, LTX caused
      a rapid and sustained elevation in the intracellular levels of Ca2+. These
      morphological and biochemical changes are consistent with the notion of
      programmed cell death.

PMID- 8301212
TI  - Secretion of TNF-alpha by alveolar macrophages in response to Candida albicans
      mannan.
AB  - Resident alveolar macrophages (AM phi) were tested for their ability to respond
      to Candida albicans mannan. AM phi were found to produce tumor necrosis factor
      alpha (TNF-alpha) in vitro in response to mannan stimulation. TNF-alpha secretion
      was measured using ELISA and L929B cellular cytotoxicity assays. Cytotoxicity was
      neutralized in parallel L929B cell cultures by the addition of rabbit anti-TNF
      alpha antibody. Mannan preparations were found to be free of contaminating LPS by
      Limulus assay. When AM phi were cultivated for 18 h at 37 degrees C, 67
      micrograms of mannan stimulated the secretion of approximately 207 U/ml of TNF
      alpha. By comparison, AM phi treated with 6.7 micrograms of LPS secreted
      approximately 257 U/ml of TNF-alpha. Optimal TNF-alpha production occurred
      between 9 and 18 h after mannan stimulation. Disparate mechanisms for stimulation
      of TNF-alpha secretion were suggested by differential sugar blockade of LPS- and
      mannan-induced TNF-alpha secretion. The addition of 2% D-mannose or 2% alpha
      methyl-D-mannoside to AM phi cultures blocked mannan- but not LPS-stimulated TNF
      alpha secretion. Furthermore, the addition of rabbit anti-mannan antibody to
      mannan-coated plastic culture dishes prevented TNF-alpha secretion by the mannan
      sensitive RAW 264.7 cell line. Moreover, the data suggest that C. albicans mannan
      stimulated AM phi to secrete TNF-alpha by an LPS-independent receptor mechanism
      which may also function as a mannose receptor.

PMID- 8301213
TI  - Inhibition of human interferon-gamma expression by antisense
      oligodeoxynucleotides.
AB  - We investigated 12 antisense oligodeoxynucleotides, complementary to different
      regions of the human interferon-gamma (HuIFN-gamma) gene, for their ability to
      inhibit HuIFN-gamma production in cultures of single donor total leukocytes or
      lymphocytes (95% purity). Out of seven oligomers, specific for a sequence
      including the translation initiation codon, 15 to 21 nucleotides long, the one
      resulting in the greatest inhibition was the 16-mer. An inhibitory effect of 90%
      could be achieved when the oligomer was added to cultures of lymphocytes in
      separate doses. Three other 16-mers, complementary to a sequence in the 5'
      noncoding region, in the coding region, or at the donor splice junction of the
      third intron respectively, were inhibitory to a lesser extent. Two 16-mers, one
      complementary to a sequence at the donor splice junction of the second intron and
      one specific for a sequence in the 3' untranslated region, showed no effect.

PMID- 8301214
TI  - gp120 HIV envelope glycoprotein increases the production of nitric oxide in human
      monocyte-derived macrophages.
AB  - The effect of recombinant gp120 HIV envelope glycoprotein on the generation of
      free radicals by monocyte-derived macrophages (MDM) was measured by EPR spin
      trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). After 1 day in culture,
      MDM produced a spin trap adduct of DMPO with hyperfine splitting constants
      superimposable on those of DMPO-OH. The addition of gp120 to MDM increased the
      production of DMPO-OH and after 1 h, the amount of DMPO-OH produced by 40
      micrograms/ml gp120 was about 300% that of untreated MDM. The use of selective
      inhibitors suggested the participation of the nitric oxide/L-arginine oxidative
      pathway, but did not provide evidence for trapping of hydroxyl radical or other
      oxygen free radicals. The specificity of gp120 was proven by two different anti
      gp120 antibodies that either inhibited (polyclonal) or increased (monoclonal) the
      production of free radicals. Dexamethasone inhibited the effect of gp120,
      suggesting the possible involvement of an inducible nitric oxide (NO) synthase.
      Moreover, treatment of MDM with gp120 for 15 h increased in a dose-dependent
      manner the production of NO2-, a stable end product of NO. Soluble CD4 did not
      modify the intensity of the DMPO-OH adduct, whereas yeast mannan and Ca(2+)
      chelators abolished the increase in the DMPO-OH signal induced by gp120. These
      data suggest the possible involvement of mannose-specific endocytotic lectin of
      MDM. The reaction of DMPO with sodium nitroprusside, an organic nitrate that
      releases NO, also produced DMPO-OH. Our findings indicate that gp120 increases
      free radical production from MDM as detected by spin-trapping methods, and that
      the spin trap adduct results from a reaction involving NO or closely related
      oxidized derivatives.

PMID- 8301215
TI  - Comparison of leukotriene B4 and D4 effects on human eosinophil and neutrophil
      motility in vitro.
AB  - The motility of isolated normal human peripheral blood eosinophils and
      neutrophils in response to exogenous leukotrienes B4 and D4 was examined by means
      of a modified under-agarose technique and a novel quantitative sampling strategy.
      Leukotriene D4 was a potent chemoattractant for eosinophils, with a significant
      threshold chemotactic effect evident at 10(-10) M. The abolition of eosinophil
      chemotaxis by the potent and selective peptide-leukotriene-antagonist SK&F 104353
      indicated the pharmacological specificity of the leukotriene D4-induced response.
      The chemokinetic response of eosinophils to leukotriene D4 generally did not
      differ significantly from spontaneous migratory activity of unstimulated cells.
      Leukotriene D4 did not, however, alter directed neutrophil motility until a very
      high concentration (10(-5) M) was achieved, although significant neutrophil
      chemokinesis relative to unstimulated movement was observed over the tested
      concentration range. Directional emigration of both eosinophils and neutrophils
      was induced by leukotriene B4 at concentrations as low as 10(-8) M. Analysis of
      leukocyte orientations provided evidence that chemokinetic responses were not
      being interpreted as indications of chemotactic behavior. These studies suggest
      that leukotriene D4 may behave as a potent and selective chemoattractant for
      human eosinophils at physiologically relevant concentrations.

PMID- 8301216
TI  - TGF-beta 1 inhibits both endotoxin-induced prostaglandin synthesis and expression
      of the TIS10/prostaglandin synthase 2 gene in murine macrophages.
AB  - Activated macrophages produce substantial quantities of paracrine mediators,
      including cytokines, nitric oxide, and prostaglandins. Transforming growth factor
      beta 1 (TGF-beta) is a potent modulator of immune function. TGF-beta inhibits the
      cytotoxic activity of endotoxin/lipopolysaccharide (LPS)-activated macrophage
      cell lines and primary macrophage cultures, reducing their expression of
      cytokines and nitric oxide. In this report we demonstrate that TGF-beta also
      attenuates the LPS-induced synthesis and secretion of prostaglandin E2 in murine
      RAW 264.7 macrophage cells. Macrophage activation also induces accumulation of
      the recently described ligand-responsive prostaglandin synthase (PGS) TIS10/PGS
      2. While TGF-beta alone has no effect on expression from the TIS10/PGS-2 gene,
      this cytokine inhibits LPS-induced TIS10/PGS-2 protein accumulation and
      synthesis, as well as LPS-induced TIS10/PGS-2 message accumulation in RAW 264.7
      cells. TGF-beta concentrations in the range of 0.1-1.0 ng/ml (4-40 pM) maximally
      inhibit LPS-induced TIS10/PGS-2 message accumulation. In contrast, neither LPS
      nor TGF-beta has any effect on the level of PGS-1 (EC 1.14.99.1) message. TGF
      beta also attenuates LPS-induced accumulation of unspliced TIS10/PGS-2
      transcripts in RAW 264.7 cells, suggesting that this cytokine exerts its effects
      on TIS10/PGS-2 expression at the transcriptional level. TGF-beta inhibits the LPS
      induced accumulation of TIS10/PGS-2 protein and message in cultured murine
      peritoneal macrophages, as well as in macrophage cell lines.

PMID- 8301217
TI  - Determination of leukotriene effects on human neutrophil chemotaxis in vitro by
      differential assessment of cell motility and polarity.
AB  - The effects of leukotriene (LT) B4 and D4 on the motility of human peripheral
      blood neutrophils were investigated employing a novel analytical method. Using
      the under-agarose technique, migration distance and vectorial orientation of
      neutrophils in response to selected LT concentrations were determined with the
      aid of digital image processing. Neutrophil polarization induced by a chemotactic
      gradient was very apparent even at fields taken adjacent to the cell seeding well
      where little directional cell motility had occurred. Thus, cell polarization
      appeared to be the earliest response to chemoattractive LTs. Cell motility
      occurred in a dose-dependent manner to LTB4 according to determination of the
      leading edge. LTD4 produced similar effects on neutrophil polarization and
      motility, but these occurred only at very high concentrations. These data support
      the view that vectorial orientation is a prerequisite for directional migration
      of cells and it is also feasible that these are separately regulated events.
      Furthermore, our studies confirm that LTB4 and, to a much lesser extent, LTD4 are
      chemotactic for human peripheral blood neutrophils.

PMID- 8301218
TI  - Effects of spaceflight on the number of rat peripheral blood leukocytes and
      lymphocyte subsets.
AB  - Experiments were carried out on peripheral blood leukocytes and spleen
      lymphocytes from 29 male rats that were flown during the Spacelab Life Sciences 1
      (SLS-1) nine-day mission on the shuttle Columbia in June 1991 and on appropriate
      ground controls. On the day of landing, there was a significant decrease in the
      total white blood cell counts (P < 0.0001) of flight animals in comparison to
      controls. There was also a significant decrease in the absolute number of
      lymphocytes (P < 0.0001) and monocytes (P < 0.0001) in the flight animals. A
      slight decrease in the absolute number of eosinophils and a slight increase in
      the number of neutrophils were observed at landing, compared with preflight
      values. Immunophenotyping of the peripheral blood and spleen lymphocytes of
      flight and control animals indicated that, on the day of landing, there was a
      decrease in the absolute number of CD4 and CD8 positive cells and B lymphocytes.
      However, relative percentages of peripheral blood CD4+, CD8+, and B cells were
      not found to be depressed. No differences were discerned in the percent
      reactivity of spleen lymphocytes of flight animals compared with controls. The
      observed decrease in the number of leukocytes and lymphocytes at the immediate
      postflight period was transient and all values returned to the control levels by
      nine days postflight.

PMID- 8301219
TI  - Involvement of CD4 in interleukin-6 secretion by U937 monocytic cells stimulated
      with the lectin jacalin.
AB  - The lectin jacalin is mitogenic for CD4 expressing T lymphocytes, interacts with
      the CD4 molecule, and inhibits HIV infection of CD4+ cells. In the present study
      the effect of jacalin was tested on cells from the monocyte/macrophage lineage
      that also express the CD4 molecule. We used CD4+ promyelomonocytic U937 cells
      differentiated towards the monocytic/macrophage lineage with either a mixture of
      two physiological agents, retinoic acid (RA) and 1 alpha,25-dihydroxyvitamin D3
      (VD), or the exogenous drug phorbol myristate acetate (PMA). The cells resulting
      from these treatments differed in term of CD4 expression. We focused our
      attention on interleukin-6 (IL-6) production, which implies an activation of the
      cells differentiated along both pathways. In CD4+ RA/VD-treated cells, jacalin
      induced a 10-fold higher IL-6 secretion than did lipopolysaccharide (LPS). This
      jacalin-induced IL-6 production was inhibited by agents interacting with CD4
      (anti-CD4 mAbs and HIV recombinant gp120) or by recombinant soluble CD4. In
      contrast, the CD4- PMA-differentiated U937 cells did not secrete any IL-6 upon
      jacalin treatment, while they demonstrated a response to LPS similar to that of
      the RA/VD-differentiated cells. Together with the fact that jacalin interacts
      with CD4, these results provide evidence of the involvement of a CD4 dependent
      pathway in IL-6 production.

PMID- 8301220
TI  - Influence of interleukin-2 infusion on cell cycle kinetics in the Walker-256
      carcinosarcoma.
AB  - The effect of recombinant human interleukin-2 (IL-2) on tumor cell cycle kinetics
      was evaluated in rats bearing the Walker-256 carcinosarcoma. Seven days after
      implantation, tumor-bearing rats were infused intravenously with IL-2 at a dose
      of 500 mg/kg body weight or 5% dextrose for 6 h. Tumor cell mean DNA synthesis
      time (TDNA), labeling index, potential doubling time (Tpot), and growth fraction
      (GF) were determined in vivo by use of bromodeoxyuridine (BrdUrd) pulse labeling
      and bivariate BrdUrd/DNA analysis using flow cytometry. IL-2 treatment
      significantly reduced the relative number of S-phase cells by 11.9% and increased
      the number of cells in the G0/G1 phase by 9.4%. The labeling index was reduced
      from 41.3 +/- 2.5% to 32.7 +/- 1.2% (P < .01). Estimates of TDNA derived from the
      change in BrdUrd movement relative to DNA content were not affected by IL-2
      treatment. Based on these cytokinetic changes, IL-2 infusion significantly
      increased tumor Tpot from 15.3 +/- 0.3 h to 21.5 +/- 0.2 h (P < .001) and reduced
      GF from 1.01 +/- 0.07 to 0.83 +/- 0.01 (P < 0.001). The inhibitory effect of IL-2
      infusion on tumor cell growth, which may be either direct or secondarily mediated
      by other factors, contrasts with other stimulatory effects of this cytokine on
      lymphoid cell proliferation.

PMID- 8301221
TI  - Quantitative discrimination of hepatic reticuloendothelial clearance and
      phagocytic killing.
AB  - An in vivo assay to quantify simultaneously two important components of hepatic
      reticuloendothelial system (RES) function--clearance and phagocytic killing--was
      developed in the rat. Intravenously injected E. coli labeled with Na51Cr and 5
      [125I]-iodo-2'-deoxyuridine were cleared rapidly from the blood primarily by the
      liver. While hepatic 51Cr levels remained stable for 24 h following inoculation
      and provided a reliable measurement of clearance, hepatic 125I decreased over
      time. Hepatic 125I, calculated by sampling whole liver homogenates, accurately
      reflects the number of viable bacteria recovered from quantitative cultures of
      the same homogenates, thus validating this assay as a measure of bacteria
      killing. Pre-treatment of rats with substances previously shown to affect RES
      function (gadolinium, zymosan, and sheep erythrocytes) were found to selectively
      modulate clearance and/or killing. The correlation between hepatic isotope levels
      and viable hepatic bacteria, the gold standard for assessing the capacity of the
      liver to remove organisms from the blood and kill them, was preserved under
      conditions of up- and down-regulation of RES function. The ability to
      quantitatively discriminate two distinct components of the hepatic RES should
      provide a useful tool for future investigations of altered RES function.

PMID- 8301222
TI  - Intracellular hydrogen peroxide and superoxide anion detection in endothelial
      cells.
AB  - One of the objectives of studying endothelial cells in vitro is to evaluate
      neutrophil-endothelial cell interactions including potential consequences of
      oxidant-mediated damage to the endothelial cell. Current understanding of
      endothelial cell oxidative function is derived primarily from the measurement of
      extracellular products. We utilized 2 dyes, 2',7'-dichlorofluorescein diacetate
      (DCFH-DA) and hydroethidine (HE), which measure hydrogen peroxide (H2O2) and
      superoxide anion (O2-) respectively, for their suitability to monitor oxidative
      mechanisms in endothelial cells and to provide a reliable measure of
      intracellular oxidants. Endothelial cells stained with DCFH-DA and stimulated
      with H2O2 exhibited an increase in the fluorescent product 2',7'
      dichlorofluorescein (DCF) (measure of intracellular H2O2) which peaked at 10 min.
      Endothelial cells stained with HE and stimulated with H2O2 exhibited an increase
      in the fluorescent product ethidium bromide (EB) (measure of intracellular O2-)
      which lasted for approximately 60 min. Superoxide dismutase increased DCF
      fluorescence in endothelial cells stimulated with H2O2 by 158%. Allopurinol
      (xanthine oxidase inhibitor) reduced DCF and EB fluorescence by 48% and 37%
      respectively in endothelial cells stimulated with H2O2. Catalase completely
      inhibited an increase in DCF or EB fluorescence in endothelial cells stimulated
      with H2O2. There was a direct correlation between mean DCF and EB fluorescence
      intensity and the concentration of H2O2 or the number of phorbol 12-myristate 13
      acetate-activated neutrophils added to endothelial cells. We conclude from these
      studies that DCFH-DA and HE can be used to measure intracellular H2O2 and O2- in
      endothelial cells and that the xanthine oxidase pathway for intracellular O2-
      production accounts for approximately 40% of the total intracellular O2-
      generated in endothelial cells after stimulation with H2O2. The combination of
      image cytometry and flow cytometry will be important for future evaluations of
      endothelial cell function.

PMID- 8301223
TI  - Vascular transcellular signaling.
AB  - Thus, it is apparent that humoral factors released during inflammation can affect
      cholesterol metabolism in arterial cells during atherogenesis. These humoral
      factors released from the macrophage, endothelium, or smooth muscle can modify
      the cytokine/growth factor/eicosanoid network in the vessel wall in either a
      paracrine or autocrine manner (6, 40). We also postulate that this could result
      in alterations in native LDL induced by endothelium (6, 40). Therefore,
      regulation of the cytokine/growth factor network by eicosanoids may represent an
      important aspect of arterial responsiveness to injury, as well as progression of
      intimal hyperplasia and CE deposition in a setting of inflammatory cell
      activation. Recent understanding of the biochemistry of eicosanoids and the
      metabolic consequences of these biological response modifiers has helped us to
      further develop this concept as it relates to mechanisms involving cholesterol
      delivery and trafficking within the vessel wall during thrombo-atherosclerosis.
      In this review, we have attempted to highlight recent data which support our
      classification system for cell-cell interactions, and document that eicosanoids
      and cytokines released from one cell can activate corresponding receptors on
      neighboring cells. They can interact with each other in this "cross talk"
      phenomenon during transmembrane signaling. Recent evidence demonstrating that
      phosphorylation reactions involving protein kinases A and C and tyrosine protein
      kinase, coupled with the highly regulated eicosanoid pathway and the DAG
      phosphatidylinositol system, appears to have a major impact in our understanding
      of at least three processes related to atherogenesis: 1) cholesterol delivery, 2)
      intracellular cholesterol processing, and 3) cholesterol efflux. Identification
      of these diverse pathways associated with transmembrane signaling have helped us
      to define processes related to thrombosis since they share common pathways in a
      complex arteriopathy during atherogenesis.

PMID- 8301224
TI  - Contribution of apoB-48 and apoB-100 triglyceride-rich lipoproteins (TRL) to
      postprandial increases in the plasma concentration of TRL triglycerides and
      retinyl esters.
AB  - After the ingestion of a fat-rich meal, there is a postprandial increase in the
      plasma concentration of both apolipoprotein B-48- and apoB-100-containing
      triglyceride-rich lipoproteins (apoB-48 and apoB-100 TRL). In order to determine
      the contribution of these lipoproteins to postprandial lipemia, the concentration
      of triglycerides (TG) and retinyl esters (RE) was measured in apoB-48 and apoB
      100 TRL after an oral fat load. Six normolipidemic male subjects were fed heavy
      cream (1 g fat per kg body weight) containing vitamin A (3000 retinol
      equivalents). TRL were isolated by ultracentrifugation from plasma samples
      obtained at regular intervals after the meal, and apoB-100 TRL were separated
      from apoB-48 TRL by affinity chromatography using monoclonal antibodies.
      Postprandial increase in plasma TG concentration was due to an increase in TG in
      the TRL fraction, which in turn was predominantly (82 +/- 4%) due to an increase
      in TG in apoB-48 TRL. Contribution of apoB-100 TRL to postprandial increase in
      TRL TG was 3-27% in individual subjects. ApoB-100 TRL remained a significant
      carrier of total plasma triglyceride in the fed state, as reflected by similar
      apoB-100 and apoB-48 TRL TG concentrations at 2, 4, and 6 h after the fat meal.
      Retinyl esters were regularly detected in apoB-100 TRL. Seventy-five (+/- 9)
      percent of the increase in TRL-RE was due to RE in apoB-48 TRL and 25 +/- 9% was
      due to RE in apoB-100. These data suggest that RE in plasma are not always
      associated with apoB-48-containing lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301225
TI  - Human hepatoblastoma cells (HepG2) and rat hepatoma cells are defective in
      important enzyme activities in the oxidation of the C27 steroid side chain in
      bile acid formation.
AB  - We have examined the ability of HepG2 human hepatoblastoma cells and 7800 C1
      Morris rat hepatoma cells to convert 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta
      cholestanoic acid (THCA) and 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid
      (DHCA) to cholic acid and chenodeoxycholic acid, respectively. Cell extracts from
      both these cell lines could neither form cholic acid from THCA nor from the
      activated form, THCA-CoA. This suggests that both cell lines are defective in two
      enzyme activities involved in the pathway, the microsomal THCA-CoA ligase and the
      peroxisomal THCA-CoA oxidase. Furthermore, we show that the subsequent enzymes
      are active in the conversion to bile acids, because the product of the THCA-CoA
      oxidase, 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-enoyl-coenzyme A
      (delta 24-THCA-CoA) or delta 24-THCA in the presence of THCA-CoA ligase, are
      converted to cholic acid by both cell lines. HepG2 cells were able to slowly form
      chenodeoxycholic acid and cholic acid from 5 beta-cholestane-3 alpha, 7 alpha
      diol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, respectively, in 24-
      and 96-h incubations. The rate of cholic acid formation was lower than the rate
      for chenodeoxycholic acid and there was a clear accumulation of THCA. 7800 C1
      Morris cells had no ability to form cholic acid or chenodeoxycholic acid after 96
      h incubation. We conclude that these two cell lines have defects in two enzyme
      activities involved in the peroxisomal oxidation in bile acid formation, the
      microsomal THCA-CoA ligase and the peroxisomal THCA-CoA oxidase.

PMID- 8301226
TI  - Oxidation of low density lipoprotein by thiols: superoxide-dependent and 
      independent mechanisms.
AB  - Oxidatively damaged low density lipoprotein (LDL) may cause macrophages to
      accumulate cholesterol in an unregulated manner, initiating the development of
      atherosclerotic lesions. Cultured smooth muscle cells oxidize LDL by a superoxide
      (O2.-)-dependent mechanism that requires L-cystine and redox-active transition
      metal ions in the incubation medium. To test the hypothesis that cellular
      reduction of L-cystine to a thiol might be involved, we exposed LDL to L
      cysteine, glutathione, and D,L-homocysteine. In a cell-free system each thiol
      modified LDL by a pathway that required either Cu2+ or Fe3+. Thiol- and Cu(2+)
      modified LDL underwent lipid peroxidation and exhibited a number of properties of
      cell-modified LDL, including increased mobility on agarose gel electrophoresis
      and fragmentation of apolipoprotein B-100. Superoxide dismutase inhibited
      modification of LDL by L-cysteine/Cu2+, whereas catalase and mannitol were
      without effect. In striking contrast, superoxide dismutase had little effect on
      oxidation of LDL by Cu2+ and either homocysteine or glutathione. Moreover, only L
      cysteine/Cu(2+)-modified 125I-labeled LDL was degraded more rapidly than 125I
      labeled LDL by human monocyte-derived macrophages: superoxide dismutase in the
      reaction mixture blocked the facilitated uptake of L-cysteine/Cu(2+)-modified
      125I-labeled LDL, suggesting involvement of O2.-. These results indicate that LDL
      oxidation by L-cysteine and Cu2+ requires O2.- but not H2O2 or hydroxyl radical.
      The reaction may involve the metal ion-dependent formation of L-cystine radical
      anion which is oxidized by oxygen, yielding O2.- and the disulfide. LDL modified
      by L-cysteine and smooth muscle cells exhibit similar physical and biological
      properties, indicating that thiol-dependent generation of O2.- may be the
      oxidative mechanism in both systems. Thiols also promote lipid peroxidation by
      O2(.-)-independent reactions but human macrophages fail to rapidly degrade these
      oxidized LDLs.

PMID- 8301227
TI  - Quantification of menstrual and diurnal periodicities in rates of cholesterol and
      fat synthesis in humans.
AB  - The mass isotopomer distribution analysis (MIDA) technique is applied here in men
      and menstruating women to quantify periodicities in the biosynthesis of serum
      cholesterol and very low density lipoprotein (VLDL)-palmitate. The isotopic
      enrichment of the true biosynthetic precursor (intracellular acetyl-CoA) during
      oral or intravenous administration of sodium[1-13C]- or [2-13C]acetate was
      calculated from mass isotopomer fractional abundances in free cholesterol and
      VLDL-palmitate, determined by gas chromatography-mass spectrometry (GC-MS). To
      convert fractional into absolute cholesterol synthesis rates, decay rate
      constants of plasma cholesterol were determined from the die-away curves of
      endogenously labeled high-mass isotopomers. Oral [13C]acetate was a 3-4 times
      more efficient means of labeling the precursor pool for VLDL-palmitate than was
      intravenous [13C]acetate, consistent with a splanchnic site of VLDL-fatty acid
      synthesis, whereas the precursor for free cholesterol had an intermediate
      enrichment, suggesting a contribution from extra-splanchnic tissues as well.
      Endogenous synthesis of serum cholesterol was 8-11 mg/kg per day (an estimated 65
      75% of input into serum cholesterol); it was 1.5- to 3-fold higher at night than
      during the day (37-49 mg/h at night compared to 9-23 mg/h during the day) and did
      not vary over the menstrual cycle (608-697 mg/day). In contrast, endogenous
      synthesis of fatty acids made a relatively minor contribution to body fat pools
      (1/10-1/20) of input into VLDL-palmitate) compared to dietary fat intake; it was
      greater in the day-time, and was influenced by menstrual cycle (3-fold elevated
      in the follicular phase compared to the luteal phase), and body composition
      (higher in obese men than normal weight men, r2 = 0.59 for lipogenesis vs. body
      mass index). Factors responsible for periodicities in endogenous lipid synthesis
      can be studied in humans using this approach.

PMID- 8301228
TI  - Fatty acid metabolism studies of human epidermal cell cultures.
AB  - Adult human epidermal keratinocytes grow rapidly in medium that is essential
      fatty acid (EFA)-deficient. In this medium they exhibit decreased amounts of the
      fatty acids, 18:2, 20:3, 20:4, and contain increased amounts of monounsaturated
      fatty acids. [14C]- and [3H]acetate and radiolabeled fatty acids, 16:0, 18:2, and
      20:4 were used to study the fatty acid metabolism of these cells. Label from
      acetate appeared in 14- to 20-carbon fatty acids, both saturated and
      monounsaturated. No label was seen in the essential fatty acid 18:2, 18:3, and
      20:4. Radiolabel from [9, 10-3H]palmitic acid (16:0) was detected in 16:0, 16:1,
      18:0, and 18:1. [14C]linoleic acid (18:2) was converted to 18:3, 20:2, 20:3, and
      20:4, demonstrating delta 6 and delta 5 desaturase activity in keratinocytes.
      Label from acetate, 16:0, or 18:2 was found mostly in the cellular phospholipids
      while only one third of the label from [14C]arachidonic was found in the
      phospholipids. [14C]acetate and [14C]18:2 time course data were used to construct
      a model of the metabolism of these reactants, using coupled, first-order
      differential equations. The data show that EFA-deficient keratinocytes metabolize
      fatty acids using pathways previously found in liver; they suggest the
      positioning of 18:2 desaturase and 18:3 elongase near the plasma membrane; they
      indicate that for the synthesis of nonessential fatty acids the formation of 18:0
      from 16:0 is the rate-determining step; and they show that the conversion of 18:2
      to 20:3 is rapid. These experiments demonstrate a method to study lipid enzyme
      kinetics in living cells.

PMID- 8301229
TI  - Effects of albumin and apolipoprotein C-II on the acyl-chain specificity of
      lipoprotein lipase catalysis.
AB  - In this study we used monoacid triacylglycerols of various acyl-chain lengths as
      substrates for probing the active-site structure and substrate specificity of
      lipoprotein lipase (LPL). An unexpected finding was that the albumin ligand
      binding site is accessible not only to long-chain fatty acids for its recognized
      functional role as a fatty acid acceptor, but also to short- and medium-chain
      monoacid triacylglycerol substrates. The observed striking inhibitory effect
      (99%) of albumin on the LPL-catalyzed hydrolysis of trihexanoylglycerol is
      probably the result of the high affinity interaction of albumin with this
      substrate. Spectrophotometric analyses indicated that there is one high affinity
      binding site per albumin molecule (apparent KD = 1.8 +/- 0.9 microM) for the
      interaction with trihexanoylglycerol. Despite LPL acyl-chain specificity being
      obscured by the substrate binding effect of albumin, a systematic study of the
      lipolysis reaction under various assay conditions demonstrated that
      tributyroylglycerol represents the best substrate for LPL, and the preferential
      order of LPL catalysis for both the basal and apoC-II-activated activities is: C4
      > C6 > C8 > C10 > C12 > C18:1. In some assay conditions, the presence of albumin
      affects the above-mentioned order, which can be attributed to substrate binding
      by albumin, rather than an alteration in the specificity of LPL. The synergistic
      effect of apoC-II and albumin resulted in the preferential activation of LPL for
      the hydrolysis of long-chain triacylglycerols. Even with optimal assay conditions
      for the hydrolysis of long chain triacylglycerols, there is still a preferential
      reactivity of LPL with short- and medium-chain triacylglycerols.

PMID- 8301230
TI  - Recurrent pancreatitis and chylomicronemia in an extended Dutch kindred is caused
      by a Gly154-->Ser substitution in lipoprotein lipase.
AB  - We report the molecular basis of familial chylomicronemia and recurrent
      pancreatitis in five members of a large Dutch family. All patients had normal
      plasma hepatic lipase and apoC-II levels, but absent lipoprotein lipase (LPL)
      catalytic activity and low LPL mass in postheparin plasma. The mutation in the
      LPL gene was characterized as a G715-->A substitution in the last nucleotide of
      exon 4, resulting in a substitution of Ser for Gly154. PCR amplification of exons
      4 + 5 from the patients' mRNA, followed by direct sequencing, revealed normal
      splicing of intron 4. The mutation creates a BfaI restriction site that allows
      rapid screening of family members for the mutation. Reproduction of this mutation
      in LPL-cDNA by site-directed mutagenesis, followed by transient expression in COS
      B cells, revealed production of a catalytically inactive enzyme. The Gly154-->Ser
      substitution appears in a conserved beta-sheet region, in close proximity to
      Asp156, which is part of the catalytic triad. These studies show that changes to
      residues close to Asp156 can have profound effects on catalytic activity of LPL.

PMID- 8301231
TI  - Polydeoxycholate in human and hamster feces: a major product of cholate
      metabolism.
AB  - Fecal bile acid excretion is one of the two major routes by which cholesterol is
      eliminated from the body, fecal cholesterol being the other. During their
      enterohepatic circulation, bile acids are secreted into the duodenum, pass down
      the jejunum and into the ileum where more than 95% is reabsorbed by the gut. Bile
      acids that escape reabsorption in the small intestine are metabolized by
      microorganisms in the large intestine. The major routes of metabolism are
      reported to be deconjugation, dehydroxylation, especially at the 7 alpha-hydroxy
      position, and dehydrogenation of the hydroxyl moieties. There are also some
      reports that saponifiable metabolites containing mostly deoxycholic acid form a
      major component of the bile acids found in human feces. We have identified a
      novel metabolite of cholic acid, 3 alpha-hydroxy polydeoxycholate, in both human
      and hamster feces that is the major constituent of these saponifiable
      metabolites. Furthermore, we have shown in hamsters that the animals that
      excreted more bile acid were excreting the additional bile acid as
      polydeoxycholate. As expected, there was a negative correlation between bile acid
      excretion in the feces and plasma cholesterol concentrations in these animals. We
      speculate that polydeoxycholate is formed in the lower gut of both humans and
      hamsters and that, by its formation, bile acid will be sequestered in an
      insoluble form, thus inhibiting its reabsorption by the gut. This process may
      help to reduce plasma cholesterol concentrations and coronary heart disease in
      humans.

PMID- 8301232
TI  - Content of antioxidants, preformed lipid hydroperoxides, and cholesterol as
      predictors of the susceptibility of human LDL to metal ion-dependent and 
      independent oxidation.
AB  - Oxidative modification of low density lipoprotein (LDL) has been suggested to
      play a casual role in human atherosclerosis, and prevention of LDL oxidation may
      be an effective strategy to prevent or slow the progression of this disease. It
      is important, therefore, to identify the factors that determine LDL's
      susceptibility to oxidation. We have analyzed 62 human LDL samples for content of
      antioxidants, preformed lipid hydroperoxides, and cholesterol. To investigate
      their oxidative susceptibility, the LDL samples were exposed to either a metal
      ion-dependent (Cu2+) or -independent (aqueous peroxyl radicals) oxidizing system;
      the length of the lag phase of inhibited lipid peroxidation was measured, as well
      as the rate of lipid peroxidation during the lag and ensuing propagation phases.
      The susceptibility of LDL to metal ion-dependent oxidation was not related to its
      susceptibility to metal ion-independent oxidation. A strong predictor of an
      increased susceptibility of LDL to metal ion-dependent oxidation was a decreased
      vitamin E-to-cholesterol ratio, in contrast to the vitamin E-to-protein ratio.
      Elevated levels of performed lipid hydroperoxides in LDL and an increased
      cholesterol content were also associated with an increased susceptibility of the
      lipoprotein to Cu(2+)-induced oxidation. Remarkably, a strong predictor of an
      increased susceptibility of LDL to metal ion-independent oxidation was an
      increased, rather than decreased, vitamin E content relative to protein. An
      increased cholesterol content also was associated with an increased oxidative
      susceptibility of LDL to aqueous peroxyl radicals, while preformed lipid
      hydroperoxides showed no significant correlation. Ubiquinol-10, beta-carotene,
      and lycopene, whether quantitated relative to cholesterol or protein, did not
      show significant protective effects against both metal ion-dependent and 
      independent oxidation of LDL. Our data suggest that a high lipid content of LDL,
      relative to its protein content, renders the lipoprotein more susceptible to
      oxidative modification, while vitamin E may have either a protective or promoting
      effect on LDL oxidation, depending on the oxidative stress conditions. Other
      known antioxidants in LDL do not appear to play a significant role in protecting
      LDL against oxidative modification.

PMID- 8301233
TI  - Effect of endotoxin on cholesterol biosynthesis and distribution in serum
      lipoproteins in Syrian hamsters.
AB  - Infection and inflammation increase serum triglyceride and cholesterol levels in
      rodents and rabbits. Endotoxin (LPS) has been used as a model of infection and
      its effects on triglyceride metabolism have been previously characterized. In the
      present study we demonstrate that both low (100 ng/100 g body weight) and high
      dose (100 micrograms/100 g body weight) LPS increase serum cholesterol levels in
      hamsters. The increase in serum cholesterol is first observed 16 h after LPS and
      persists for at least 24 h. This increase is primarily due to an increase in low
      density lipoprotein (LDL) cholesterol. High density lipoprotein (HDL) cholesterol
      levels decrease after LPS treatment. Both low and high dose LPS increase hepatic
      cholesterol synthesis (low dose 85%, high dose 205%) and total HMG-CoA reductase
      activity (low dose 2.97-fold, high dose 9.96-fold). However, the proportion of
      HMG-CoA reductase in the active form is reduced by LPS treatment. Additionally,
      the mass of HMG-CoA reductase protein in the liver, measured by Western blotting,
      is increased after LPS. Moreover, LPS increases hepatic HMG-CoA reductase mRNA
      levels (low dose 3.1-fold, high dose 14.2-fold). The increase in hepatic HMG-CoA
      reductase mRNA levels is first seen 4 h after LPS and persists for at least 24 h.
      In contrast, LPS had only minimal effects on hepatic LDL receptor protein and
      mRNA levels. These results suggest that LPS increases serum cholesterol levels by
      increasing hepatic cholesterol synthesis. LPS administration decreases apoE mRNA
      levels in the liver while having no effect on apoA-I mRNA levels. These results
      suggest that HMG-CoA reductase is a member of a group of hepatic proteins that
      are positively regulated by inflammatory stimuli (acute phase proteins) while
      apoE can be considered a negative acute phase protein in hamsters. It is possible
      that increases in hepatic HMG-CoA reductase provide cholesterol that allows for
      the increased production of lipoproteins and elevations in serum lipid levels
      that may be beneficial to the body's host defense.

PMID- 8301234
TI  - Cholesterol and sphingomyelin syntheses are regulated independently in cultured
      human intestinal cells, CaCo-2: role of membrane cholesterol and sphingomyelin
      content.
AB  - There is a presumed association between cellular cholesterol and sphingomyelin
      metabolism. To study this relationship in the intestine, the activity of the rate
      controlling enzyme of sphingolipid synthesis, serine palmitoyltransferase (SPT),
      and the biosynthesis of long-chain bases were characterized in cultured human
      intestinal cells, CaCo-2. Cells were then incubated with substances known to
      alter cholesterol biosynthesis, and the effect of these mediators on SPT activity
      and long-chain base synthesis was determined and compared with their effects on
      HMG-CoA reductase activity and cholesterol synthesis. The polar sterol, 25
      hydroxycholesterol, the squalene epoxide inhibitor, U18666A, and the inhibitor of
      HMG-CoA reductase, lovastatin, all significantly inhibited the synthesis of
      cholesterol without altering either SPT activity or long-chain base synthesis.
      Mevalonate, which increased cholesterol production 3-fold, also had no affect on
      SPT activity or sphingoid base synthesis. Serine, which significantly increased
      the synthesis of long-chain bases, did not alter cholesterol biosynthesis.
      Moreover, the suicide inhibitors of SPT, beta-chloroalanine and cycloserine, did
      not alter cholesterol synthesis while markedly decreasing long chain base
      synthesis. Cells were incubated with palmitic, oleic, linoleic, and
      eicosapentaenoic acids. Only palmitic acid, the preferred substrate for SPT,
      increased the production of long-chain bases. Both palmitic and oleic acids,
      however, increased the synthesis of cholesterol. Cells enriched in sphingomyelin
      had higher rates of synthesis of both cholesterol and long-chain bases compared
      to their controls. In contrast, cholesterol and long-chain base syntheses were
      significantly decreased in cells enriched in cholesterol. Control cells incubated
      with phospholipid liposomes alone had higher rates of synthesis of both
      lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301236
TI  - Regional distribution of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity
      and protein mass in the ocular lens.
AB  - We have attempted to map the regional distribution of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (HMGR) enzyme activity and protein mass along the radial
      axis of the ocular lens. Because lens plasma membrane is extremely rich in
      cholesterol and the lens must synthesize this cholesterol, the activity of HMGR
      could be a key factor controlling lens membrane formation. Lenses of young rats
      were divided into discrete fractions by gradual dissolution in a tergitol
      containing buffer; each fraction was then equated to a specific arc of the radius
      based upon its protein content. Aliquots of each fraction were assayed for HMGR
      enzyme activity and protein mass. Relative protein mass was quantitatively
      estimated by Western blotting using a monoclonal antibody to HMGR with
      immunoreactivity detected by enhanced chemiluminescence. Lens HMGR possessed a
      molecular mass of about 97 kDa and localized in the cell's insoluble fraction.
      Peak levels of both HMGR enzyme activity and protein mass were found in the outer
      5% of the lens radius; levels of both decreased precipitously from there to the
      outer 10% radius mark. This distribution paralleled synthesis of the membrane's
      cholesterol, phospholipid, and intrinsic protein. We conclude that the abrupt
      cessation of plasma membrane synthesis in the ocular lens could involve loss of
      HMGR activity over a narrow arc of the lens radius, and that this activity loss
      is due to disappearance of enzyme protein.

PMID- 8301235
TI  - Functional role of N-linked glycosylation in human hepatic lipase: asparagine-56
      is important for both enzyme activity and secretion.
AB  - Hepatic lipase (HL) and lipoprotein lipase (LPL) are evolutionarily related
      enzymes that are essential for normal lipoprotein metabolism. While much has been
      published on the structure-function relationship of LPL, little is known
      concerning the structural basis of HL action and secretion. Human HL is a
      glycoprotein and its predicted amino acid sequence contains four putative N
      linked glycosylation sites at Asn residues 20, 56, 340, and 375. We studied the
      role of these residues in the secretion and catalytic activity of hHL by analysis
      of hHL expressed in stable CHO cell lines. Using site-specific mutagenesis, the
      wild-type human HL and substitution mutants of each of the four Asn residues were
      expressed in vitro. The relative sizes of these site-specific mutants indicate
      that all four putative sites are utilized for glycosylation in CHO cells.
      Abolition of N-linked glycosylation of three (residues 20, 340, and 375) of the
      four sites did not affect enzyme secretion or activity. Mutations of Asn-56 to
      either Gln or Ala resulted in the production of a totally inactive HL which
      accumulated intracellularly but was not secreted into the culture medium.
      Therefore, Asn-56 is required for both HL enzyme activity and secretion. The fact
      that the homologous N-linked glycosylation site (Asn-43) is required for both
      enzyme activity and secretion for human LPL (Semenkovich et al. 1990. J. Biol.
      Chem. 265: 5429-5433) indicates that carbohydrate chains at this site are
      essential for the active conformation and correct folding for secretion of these
      evolutionarily related lipases. Our observations provide insight into the
      structural basis of lipase action and secretion.

PMID- 8301237
TI  - Relative effects of weight loss and dietary fat modification on serum lipid
      levels in the dietary treatment of obesity.
AB  - The independent effects of weight loss and dietary fat modification on serum
      lipids were investigated in two groups of healthy moderately obese men and women.
      In one group (sequential group, n = 19), a weight-stable low-fat, low-saturated
      fat diet (Low-Sat) was given for 7 weeks (= dietary modification), followed by a
      4.2 MJ/day deficit Low-Sat diet for 13 weeks (i.e., weight loss alone). Another
      group (simultaneous group, n = 22) received a 4.2 MJ/day deficit Low-Sat diet for
      13 weeks (i.e., weight loss+dietary fat modification). Each group was subject to
      an initial weight-stable high-fat, high-saturated fat diet for 3 weeks and a
      final weight stable Low-Sat diet for 3 weeks. Both groups lost similar amounts of
      body weight, about 13 kg, and had similar overall changes in total cholesterol,
      low density lipoprotein (LDL), cholesterol, high density lipoprotein (HDL)
      cholesterol, the HDL/LDL ratio, and triglycerides. Analysis of the separate
      effects of the Low-Sat diet without energy restriction and of weight loss in the
      sequential group showed that weight loss per se was responsible for about 50% of
      the total reduction in total cholesterol, and for about 60% and 70% of the fall
      in LDL cholesterol and triglycerides, respectively. Fat modification without
      weight loss reduced HDL cholesterol by 11.1% and the HDL/LDL ratio by 7.7%, while
      weight loss per se led to increases in HDL cholesterol of 12.5% and in the
      HDL/LDL ratio of 24.0%. We conclude that the effects of reduction in fat and
      saturated fat intake and weight loss are additive.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8301238
TI  - Estimating the fractional synthetic rate of plasma apolipoproteins and lipids
      from stable isotope data.
AB  - The use of isotopic tracer studies to quantitate parameters characterizing
      apolipoprotein metabolism is enjoying a resurgence. This is due in large part to
      the availability of a number of stable isotopes and methods to measure them
      accurately in small quantities. Most experimental protocols in which stable
      isotopes are used call for endogenous labeling of the apolipoprotein of interest
      by an infusion of a labeled amino acid. Unlike the radioactively labeled amino
      acid counterpart in which turnover studies have traditionally been carried out
      for 72 hours to 14 days, the duration of the stable isotope experiment is
      normally less than 24 hours. This has contributed to some problems related to
      estimating the kinetic parameters because simplistic formulas whose underlying
      assumptions are not applicable to the lipoprotein system under study are often
      invoked. This is particularly true for the fractional synthetic rate (FSR). The
      purpose of this review is to address some of these problems. We derive the
      formula commonly used to estimate the FSR. In so doing, the underlying
      assumptions are carefully delineated. We then discuss several ways in which the
      formula is applied. Finally, we discuss the implications of these assumptions
      when the formula is applied to specific lipoprotein systems.

PMID- 8301239
TI  - Evaluation of apoA-I kinetics in humans using simultaneous endogenous stable
      isotope and exogenous radiotracer methods.
AB  - Apolipoprotein A-I is the major apolipoprotein constituent of high density
      lipoproteins (HDL). Methods used to investigate in vivo kinetics of apoA-I
      include exogenous labeling with radioiodine and endogenous labeling with stable
      isotopically labeled amino acids. We report here a direct comparison of these
      methods to determine the in vivo kinetics of apoA-I in four normal subjects.
      Purified apoA-I was labeled with 125I, reassociated with autologous plasma, and
      injected into study subjects. At the same time, [13C6]phenylalanine was
      administered as a primed constant infusion for up to 14 hours. The kinetic
      parameters of apoA-I were determined from the 125I-labeled apoA-I plasma curves.
      For the analysis of data from stable isotope studies, very low density
      lipoprotein (VLDL) apoB-100, VLDL apoB-48, and total apoA-I were isolated by
      ultracentrifugation and subsequent preparative NaDodSO4-PAGE, hydrolyzed, and
      derivatized. The tracer/tracee ratio was determined by gas chromatography-mass
      spectrometry. Monoexponential function analysis was used to determine the
      tracer/tracee curves of VLDL apoB-100 and VLDL apoB-48, and total apoA-I. The
      mean plateau tracer/tracee ratio of VLDL apoB-100 (primarily liver-derived) was
      5.19%, whereas that of VLDL apoB-48 (intestinally derived) was only 3.74%. Using
      the VLDL apoB-100 plateau tracer/tracee ratio as the estimate of the precursor
      pool enrichment for apoA-I, the mean apoA-I residence time (RT) was 5.14 +/- 0.41
      days, compared with 4.80 +/- 0.30 days for the exogenous labeling method. The
      apoA-I RTs using these two methods were highly correlated (r = 0.874).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301240
TI  - Phonology and spelling: the case of syllabic consonants.
AB  - Two experiments were performed to explore the effects of one aspect of English
      phonology, syllabic consonants, on children's spelling. In Experiment 1,
      kindergarteners (age 6), first graders (age 7), and second graders (age 8)
      spelled words with stressed syllabic /r/, such as sir, and words with medial
      vowels, such as wet. Vowel omissions (e.g., "sr") and vowel misorderings (e.g.,
      "sre") were more common for the syllabic /r/ words than for the comparison words.
      In Experiment 2, first and second graders spelled words with unstressed syllabic
      /r/, such as wander, unstressed syllabic /l/, such as easel, and unstressed
      syllabic nasals, such as carton. Words with unstressed vowels in the second
      syllable, such as bandit, were also included. For first graders, vowel omissions
      and misorderings occurred primarily for syllabic /r/ and /l/. By second grade,
      only orthographically influenced errors on syllabic /l/ remained. The results
      show that phonology plays an important role in early spelling. They also shed
      light on the nature of children's phonological representations.

PMID- 8301241
TI  - When is a mug not a mug? Effects of content, naming, and instructions on
      children's drawings.
AB  - Two hundred seventy 5-year-old children produced a copy drawing of a transparent
      glass mug with its handle turned away. In a factorial design three factors were
      manipulated to examine their additive or independent influence on the child's
      production of either view-specific or canonical (i.e., with the handle at the
      side) depictions: the content of the mug, the label used to describe it, and the
      explicitness of instruction. The results showed, first, that each of these
      variations in task demands exerted an influence on the canonicality/view
      specificity of the children's drawings. Second, these influences were both
      facilitative and prohibitive. So, for example, general instructions prompted
      canonical drawings, while very explicit instructions elicited view-specific
      depictions. Third, each factor exerted an independent influence upon whether or
      not the handle was included--there were no interactions between factors on the
      production of the two types of picture. These results provide further evidence
      against simple associations between children's drawings and their cognitive
      abilities. They suggest that what children produce in studies of "drawing" may
      well simply inform us about the development of an understanding of adults'
      communicative intent.

PMID- 8301242
TI  - Chess expertise and memory for chess positions in children and adults.
AB  - This paper presents a replication and extension of Chi's (1978) classic study on
      chess expertise. A major outcome of Chi's research was that although adult
      novices had a better memory span than child experts, the children showed better
      memory for chess positions than the adults. The major goal of this study was to
      explore the effects of the following task characteristics on memory performance:
      (1) Familiarity with the constellation of chess pieces (i.e., meaningful versus
      random positions) and (2) familiarity with both the geometrical structure of the
      board and the form and color of chess pieces. The tasks presented to the four
      groups of subjects (i.e., child experts and novices, adult experts and novices)
      included memory for meaningful and random chess positions as well as memory for
      the location of wooden pieces of different forms on a board geometrically
      structured by circles, triangles, rhombuses, etc. (control task 1). Further, a
      digit span memory task was given (control task 2). The major assumption was that
      the superiority of experts should be greatest for the meaningful chess positions,
      somewhat reduced but still significant for the random positions, and
      nonsignificant for the board control task. Only age effects were expected for the
      digit span task. The results conformed to this pattern, showing that each type of
      knowledge contributed to the experts' superior memory span for chess positions.

PMID- 8301243
TI  - Developmental changes in understanding an illusion based on perceptual
      adaptation: effects of feedback.
AB  - Children and adults were exposed to an illusion created by perceptual adaptation,
      in which they perceived two identical bottles, held simultaneously in a different
      hand, as being different in weight. Prior research has shown that young children
      treat the perceived difference as real rather than illusory. In an initial study,
      feedback designed to signal the illusory nature of the weight difference led many
      third graders to acquire an erroneous rule. Older children and adults more often
      gave a correct response, although there was no clear evidence that they
      understood the illusion. In Study 2, confronting children with the discrepancy
      between the preillusion phase of the testing and the subsequent experience of an
      illusion helped them to infer an understanding of the illusion when the
      discrepancy was large. The results have implications for the development of the
      understanding of perceptual processes, the appearance-reality distinction, and
      the child's theory of mind.

PMID- 8301244
TI  - Auditory filter widths in children and adults.
AB  - Filter widths for six groups of subjects, adults and children ages 6, 7, 8, 9,
      and 10, were estimated using two different psychophysical approaches. Subjects
      participated in an experiment with a fixed signal level (psychophysical tuning
      curve procedure) and in an experiment having a fixed masker level (notched noise
      procedure). The psychophysical tuning curves were determined with 200-Hz-wide
      noise bands centered at 2.3, 2.6, 3.0, 3.4, and 3.6 kHz. The 200-ms, 3-kHz signal
      was fixed in level at 30 dB SPL. Notched noise thresholds were determined with
      notch widths of (delta f/f) 0.0, 0.2, and 0.4. The delta f was the distance, in
      hertz, from the center frequency, f, to the edge of symmetrically placed bands of
      noise. The bands of noise were fixed at 35-dB pressure spectrum level. Results
      revealed no significant differences between the children and the adults on
      measures of Q10, ERB, and K. The conclusion of the present study was that
      auditory filter widths from the ages of 6 to adult were not significantly
      different.

PMID- 8301245
TI  - Children's understanding of the relation between referential knowledge and
      referential behavior.
AB  - Young children often confuse what is said and meant in referential communication.
      This study determines exactly what is confused by kindergarten children, second
      graders, and fourth graders. In each of four experiments, a story listener's
      referential knowledge variously came from object details in the context and in an
      utterance, and children were asked independently to judge knowledge sufficiency
      for identifying one referent in a display, and whether the knowledge came from
      the utterance alone. In Experiments 1 and 2, experimenter identification of the
      correct referent was manipulated to determine if children confuse internal
      representations of information knowledge and referential behavior, or behavior
      and the real world referent, in determining the listerner's knowledge. In other
      experiments, the consistency of referential behavior with the correct referent
      was manipulated to determine the basis of children's knowledge assessments.
      Overall the results show that children's say-mean confusion varies depending on
      situational factors and variably reflects children's use of internal
      representations and external referential behavior in assessing knowledge.

PMID- 8301246
TI  - Four-year-olds' disambiguation of action and object word reference.
AB  - Preschool-age children show a very strong tendency to map a novel noun onto an
      unfamiliar rather than a familiar object. This so-called disambiguation effect
      has been interpreted as evidence that youngers expect object labels to be
      mutually exclusive. In Experiment 1, 4-year-olds were observed to map a novel
      verb onto an unfamiliar action about twice as often as they mapped it onto a
      familiar one. When the unfamiliar action had been preexposed, but the familiar
      one had not, the mapping preference was eliminated. In Experiment 2, 4-year-olds
      mapped a novel noun onto an unfamiliar object about five times as often as they
      mapped it onto a familiar object, and this tendency was not affected by
      preexposure. Even when action embedding and question complexity were controlled,
      the disambiguation effect was stronger for object than for action words. An
      account is presented in which two lexical principles, Mutual Exclusivity and
      Feeling of Novelty, are hypothesized to apply differently to action than to
      object words.

PMID- 8301248
TI  - Effect of exogenous estradiol applied at different embryonic stages on sex
      determination, growth, and mortality in the leopard gecko (Eublepharis
      macularius).
AB  - Temperature-dependent sex determination (TSD) occurs in three orders of reptiles.
      Several studies have examined the ability of estradiol to produce female
      hatchlings incubated at a male-producing temperature. The results of these
      experiments support the idea that estradiol could be used as a powerful tool in
      the conservation of endangered species with TSD by manipulating hatchling sex
      ratios. However, these experiments have concentrated on the mechanism of
      determination. This experiment was designed to test the efficacy of various
      dosages of estradiol applied at two different stages to alter the hatchling sex
      ratio as well as determining the potential use of such manipulation for
      conservation efforts by monitoring egg mortality and hatchling growth. The
      leopard gecko (Eublepharis macularius) exhibits TSD and reaches reproductive
      maturity in less than one year, making it an excellent model for evaluating the
      long-term effects of estradiol. The results demonstrate that estradiol has a dose
      dependent effect on the hatchling sex ratio while only high dosages applied at
      the later stage of development showed increased mortality. Estrogen-determined
      females grew at the same rate as temperature-determined females and have produced
      viable hatchlings. Estradiol treatment of eggs from endangered species may
      provide a method of insuring female offspring when the TSD pattern is unknown or
      equipment for controlled incubation is unavailable.

PMID- 8301247
TI  - The development of short-term memory span: separable effects of speech rate and
      long-term memory.
AB  - We report an experiment investigating the mechanisms responsible for short-term
      memory span and its development by examining the relationship between memory span
      and speech rate for words and nonwords of differing spoken lengths. Linear
      functions related memory span to speech rate for both words and nonwords in
      children of different ages. The functions for nonwords had equivalent slopes
      (interpreted as reflecting a contribution from a speech-based process) but lower
      intercepts (interpreted as reflecting a contribution from a long-term memory
      component) than the functions for words. Children in both age groups studied
      showed evidence of a relationship between speech rate and memory span and part of
      the difference in memory span between age groups appears to reflect a difference
      in speech rate. However, there is also evidence that the long-term memory
      component of memory span shows greater efficiency in older children.

PMID- 8301250
TI  - Isosmotic modulation of cell volume and intracellular ion activities during
      stimulation of single exocrine cells.
AB  - Stimulation of salivary secretion is associated with a rise of [Ca2+]i in acinar
      cells. We examined the osmotic and ionic consequences of activation of Ca(2+)
      dependent K+ and Cl- channels, by simultaneous optical determinations of cell
      volume and [Ca2+]i, [Cl-]i or [Na+]i during muscarinic stimulation of single
      salivary acinar cells, using a differential interference contrast (DIC)
      fluorescence microscope. Carbachol caused a rapid rise of [Ca2+]i, as well as a
      substantial cell shrinkage. Despite variability in the level and kinetics of the
      subsequent sustained phase of the [Ca2+]i response, cell volume was correlated
      with [Ca2+]i in all cases. Elevated [Ca2+]i was both necessary and sufficient to
      cause these changes in cell volume. The proposition that changes in cell volume
      reflected changes in cell solute content was confirmed by simultaneously
      measuring [Cl-]i and cell volume. Simultaneous determinations of cell volume and
      [Na+]i indicated that the initial cell shrinkage was due entirely to K+ and Cl-
      efflux. Subsequent to the initial shrinkage, [Na+]i rose to high levels,
      primarily due to activation of Na+/H+ exchange. Thus, modulation of ion transport
      activities under isosmotic conditions results in substantial changes in cell
      solute content and cell volume. Subsequent to the early Ca(2+)-induced changes in
      these parameters, other transporters become active, but it is unclear what
      signals their activation. Cell swelling by osmotic dilution of the bath resulted
      in compensatory cell shrinkage (RVD) which was sensitive to K+ and Cl- gradients.
      Nevertheless, a rise of [Ca2+]i was not necessary for RVD. Osmotic shrinkage
      and/or cell acidification were insufficient to activate Na+ influx.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301249
TI  - Serial repetition of cilia pairs along the tail surface of an ascidian larva.
AB  - Regularly spaced cilia pairs were found in two rows immediately opposite to each
      other mid-dorsally and mid-ventrally along the larval tail surface of the
      ascidian protochordate Ciona intestinalis. There were approximately ten such
      equidistantly placed dorsal-ventral sets embedded in the matrix of the
      extracellular larval test which forms the flattened vertical tail fin. These
      immotile cilia originate from pairs of cell bodies in mid-dorsal and mid-ventral
      peripheral nerves running beneath the tail epidermis. The cilia and neural cell
      bodies were visualized by immunocytochemical staining with anti-tubulin
      antibodies; their nature was confirmed by ultrastructural examination. This
      pattern of cilia and neural cell body placement is conceivably related to the
      segmentation found in vertebrates.

PMID- 8301252
TI  - Channels for ions and amino acids in kidney cultured cells (MDCK) during volume
      regulation.
AB  - A cell line from canine kidney (MDCK) was studied in hypotonic conditions to
      determine the transport mechanisms involved during regulatory volume decrease
      (RVD). It was found that RVD was related to a loss of K+, Cl- and amino acids.
      Membrane potential measurements during RVD have shown a hyperpolarization
      followed by a depolarization, implying that ion fluxes were probably occurring
      through channels. Quinine was found to inhibit RVD, the ion fluxes and the amino
      acid losses. A long preincubation in Ca(++)-free EGTA medium had no effect on RVD
      in cells exposed to the hypotonic medium. Single channel experiments with the
      patch clamp technique have shown that cell swelling rapidly activates K+ channels
      and, after a 30 sec delay, Cl- channels. The K+ channel was highly selective and
      had a linear I-V curve with a conductance of 25 pS. The Cl- channel was an
      outward rectifier with conductances of 63 and 26 pS. It was not very selective;
      replacing Cl- with NO3- did not change the I-V curve and did not affect RVD. The
      amino acid losses during RVD were studied with HPLC. It was found that three of
      them, glutamate, taurine and glycine, had large concentrations and were lost at
      different rates. Their fluxes during RVD depended linearly on their external
      concentrations, meaning that the transport process was diffusional. Single
      channel measurements with glutamate, aspartate or taurine in place of Cl- have
      shown that these amino acid losses occurred through the Cl- channel.

PMID- 8301251
TI  - Evidence for the role of actin filaments in regulating cell swelling.
AB  - Actin filaments could play a role in regulation of cell swelling by two distinct
      mechanisms. One is by a tensile mechanism involving the coordinated interaction
      of actin and actin-associated proteins with all plasma membrane domains. The
      actin-membrane linkage would restrain cell swelling in the event of the influx of
      water. In shark rectal gland cells, conditions that cause massive cell swelling
      (i.e., high K medium, exposure to mercurials) are associated with disruption of
      membrane-associated actin filaments. Under conditions that result in only
      moderate swelling (Na-pump inhibition, Li substitution) the actin filaments
      remain associated with the cell membrane. Thus, in this cell type, disruption of
      the actin-membrane organization is correlated with increased swelling. Another
      mechanism by which actin could limit cell swelling is via regulation of ion
      transport proteins that are activated by cell swelling. This could be
      accomplished by a vesicle transport and insertion mechanism that delivers ion
      transport units to the cell membrane or by interaction with transport proteins
      already present in the membrane. Cell-attached patch clamp studies of RCCT-28A
      cells exposed to hypotonic medium demonstrated the activation of Cl-channel
      activity coincident with an alteration in actin. Activation of the channel was
      mimicked by stretching the membrane. Exposure of inside-out patches to
      cytochalasins also increased Cl-channel activity. Treatment of isolated patches
      with phalloidin inhibited stretch-induced activation. Thus, regulation of a
      volume-sensitive Cl-channel appears to be directly related to the state of
      organization of actin filaments.

PMID- 8301253
TI  - Molecular basis for osmoregulation of organic osmolytes in renal medullary cells.
AB  - Renal medullary cells are naturally exposed to extremely high and variable
      interstitial concentrations of NaCl and urea, consequent to operation of the
      urinary concentrating mechanism. They respond by accumulating large and variable
      amounts of sorbitol, glycerophosphocholine (GPC), glycine betaine (betaine), myo
      inositol (inositol), and taurine both in vivo and in cell cultures. Sorbitol is
      synthesized from glucose, catalyzed by aldose reductase. Hypertonicity increases
      aldose reductase activity by raising this enzyme's transcription, mRNA level, and
      translation, and thereby increases production of sorbitol. GPC is synthesized
      from choline via phosphatidylcholine. A combination of high NaCl plus urea does
      not increase GPC synthesis, but does reduce its degradation by inhibiting
      GPC:choline phosphodiesterase. Betaine, inositol and taurine are taken up into
      the cells, each by a different sodium-dependent transporter. Hypertonicity
      increases mRNAs of all three transporters. This is due to increased transcription
      (at least of the inositol and betaine transporters). The eventual result is
      greater betaine, inositol and taurine uptake and accumulation. Osmoregulation of
      net sorbitol and GPC synthesis and of betaine, inositol and taurine transport is
      slow, requiring hours to days. However, following an acute fall in tonicity,
      these organic osmolytes exit from the cells within minutes, via specialized
      efflux mechanisms. As demonstrated by cloning efficiency studies, renal cell
      survival and growth following hypertonicity depend on the sum of all organic
      osmolytes that are accumulated; altering one experimentally changes the others to
      maintain a nearly constant total. Methylamine accumulation protects these cells
      against high urea; the methylamine that is preferentially accumulated in response
      to high urea is GPC.

PMID- 8301254
TI  - Introduction: cellular volume regulation--mechanisms and control.

PMID- 8301255
TI  - Problems in the understanding of cell volume regulation.
AB  - The constancy of cell volume under physiological conditions is generally thought
      to reflect a balance between solute influx and efflux and is therefore critically
      dependent on the properties of the plasma membrane. Despite a number of
      unanswered questions, a large amount of experimental data can be accommodated
      within this pump-leak framework and can by analysed using the simple assumptions
      of osmotic equality between cells and their surrounding fluid, and fluid
      electroneutrality. Experimentally, cell volume may be altered in vitro either by
      changing cell solute content under isosmotic conditions or by changing medium
      osmolality. Exposure to anisosmotic media may provoke a variety of cell responses
      that minimise the volume change. However, much of this experimental work has been
      performed under extreme conditions in vitro that would never be experienced by
      vertebrate cells in vivo; its relevance to pathophysiological situations is
      questionable. It is argued that regulation of cell volume should not be seen in
      isolation but as part of the process, cell homeostasis, by which cells attempt to
      minimise changes in composition when faced with perturbations in their
      environment. Given the variety of processes and the large numbers of membrane
      transporters, an understanding of how cells respond to such perturbations
      requires a combination of modelling and experimentation. A simple example of this
      approach is presented.

PMID- 8301256
TI  - Regulation of mammalian brain cell volume.
AB  - Maintenance of brain cell volume is of crucial importance for normal central
      nervous system (CNS) function. This review considers volume regulation primarily
      in response to disturbances of body fluid osmolality. Brain cells counter the
      tendency to swell or shrink by appropriate adjustment of their internal osmotic
      potential. This is achieved by loss or uptake of inorganic ions and low molecular
      weight organic solutes (osmolytes). The latter comprise mainly amino acids,
      myoinositol, choline, and methylamines. Taurine may be of particular importance
      in volume control, especially in young animals. Brain cell volume regulation,
      however, is only one contributory factor to maintenance of constant brain volume
      (water content), and operates in parallel with important alterations in bulk
      fluid and electrolyte movement across the blood-brain barrier and between the
      interstitium and cerebrospinal fluid, which themselves moderate the requirement
      for transient alteration in cell volume during acute osmotic imbalance. Although
      altered cerebral content of inorganic ions and osmolytes are usually regarded as
      responses, respectively, to acute and chronic osmotic disturbances, osmolytes
      (especially taurine) may also participate in short-term cell volume regulation.

PMID- 8301257
TI  - Changes in membrane potential associated with cell swelling and regulatory volume
      decrease in barnacle muscle cells.
AB  - Our aim was to test the effect of hypotonicity and extracellular Ca2+ (Cao) on
      cell volume and membrane potential (VM) in barnacle muscle cells. Under isotonic
      conditions the resting VM of isolated cells mounted in the experimental chamber
      exposed to either Ca(2+)-free or Ca(2+)-containing (11 mM) solutions was -46.3 +/
      1.0 mV (n = 24) and -56.2 +/- 0.9 mV (n = 38), respectively. In the absence of
      Cao, the cells depolarized at a rate of 2.3 +/- 0.47 mV/hr; the presence of Cao
      reduced this rate of depolarization by 2.9-fold. Both in the absence or presence
      of Cao, the cells swelled in response to hypotonicity but underwent regulatory
      volume decrease (RVD) when Cao was present. Addition of the Ca2+ channel blocker,
      verapamil (0.1 mM), inhibited the Cao-dependent RVD. The percentage of cells
      responding with RVD increased with larger hypotonic challenges. There was a Cao
      independent direct relationship between cell swelling and membrane depolarization
      which can be explained by dilution of the concentration of intracellular K+
      ([K+]i). RVD was accompanied by a small hyperpolarization (3.0 +/- 0.38 mV/2 hr)
      which may represent increases in [K+]i during cell shrinking and activation of a
      conductive pathway. The results indicate the following: (1) the presence of Cao
      stabilizes VM; (2) cell swelling produces a depolarization which can be explained
      by dilution of [K+]i; (3) cell swelling activates a verapamil-sensitive Ca2+
      influx responsible for promoting RVD; and (4) RVD is accompanied by a
      hyperpolarization which may result from activation of a conductive pathway.

PMID- 8301258
TI  - Gating-dependent mechanism of 4-aminopyridine block in two related potassium
      channels.
AB  - 4-aminopyridine (4AP) is widely used as a selective blocker of voltage-activated
      K+ currents in excitable membranes, but its mechanism and site of action at the
      molecular level are not well understood. To address this problem we have analyzed
      4AP block in Kv2.1 and Kv3.1, mammalian representatives of the Drosophila Shab
      and Shaw subfamilies of voltage-gated K+ channels, respectively. The two channels
      were expressed in Xenopus oocytes and analyzed at both the macroscopic and single
      channel levels. Whole cell analysis showed that 4AP sensitivity of Kv3.1 was
      approximately 150 times greater than that of Kv2.1. Patch clamp analysis revealed
      that the mechanism of 4AP block in both channels was qualitatively similar. 4AP
      reached its blocking site via the cytoplasmic side of the channels, the ON rate
      for block was strongly accelerated when channels opened and the drug was trapped
      in closed channels. Single channel analysis showed that 4AP decreased burst
      duration and increased the latency-to-first-opening. These effects were found to
      be related, respectively to drug ON and OFF rates in the activated channel.
      Kv3.1's high 4AP sensitivity relative to Kv2.1 was associated with both a slower
      OFF rate and therefore increased stability of the blocked state, as well as a
      faster ON rate and therefore increased access to the binding site. Our results
      indicate that in both channels 4AP enters the intracellular mouth to bind to a
      site that is guarded by the gating mechanism. Differences in channel gating as
      well as differences in the structure of the intracellular mouth may be important
      for specifying the 4AP sensitivity in related voltage-gated K+ channels.

PMID- 8301259
TI  - Novel Cl- currents elicited by follicle stimulating hormone and acetylcholine in
      follicle-enclosed Xenopus oocytes.
AB  - Voltage-clamp techniques were used to study the membrane currents elicited by
      follicle stimulating hormone (FSH) and acetylcholine (ACh) in follicle-enclosed
      oocytes of Xenopus laevis (follicles). Both agonists caused complex responses
      that were more evident when the follicles were in hypotonic Ringer solution (HR;
      190.4 mosM). In this medium, currents activated by FSH regularly showed three
      phases whereas currents activated by ACh displayed three to six phases. At a
      holding potential of -60 mV, FSH, and ACh responses involved combinations of
      inward and outward currents. Both FSH and ACh responses included a slow smooth
      inward component that was associated with an increase in membrane conductance,
      mainly to Cl- (S(in)). This current was strongly dependent on the osmolarity of
      the external solution: an increase in osmolarity of the HR solution of 18-20 mosM
      caused a 50% decrease in S(in). In contrast, a fast and transient Cl- current
      (F(in)) specifically elicited by ACh was not dependent on osmolarity. Both, F(in)
      and S(in) currents required the presence of follicular cells, since
      defolliculation using three different methods abolished all the response to FSH
      and at least four components of the ACh responses. The membrane channels carrying
      F(in) and oscillatory Cl- currents elicited by stimulation of ACh or serum
      receptors, were much more permeable to I- and Br- than Cl-, whereas S(in)
      channels were equally permeable to these anions. Unlike the oscillatory Cl-
      currents generated in the oocyte itself, S(in) and F(in) currents in follicle
      enclosed oocytes were not abolished by chelation of intracellular Ca2+, either
      with EGTA or BAPTA, which suggests that intracellular Ca2+ does not play a
      critical role in the activation of these currents. Our experiments show that
      S(in) and F(in) currents are quite distinct from the previously characterized
      oscillatory Cl- responses of oocytes. Moreover, the results strongly suggest that
      the FSH and ACh receptors, the Cl- channels mediating the F(in) and S(in)
      currents, together with the necessary elements for their activation, are all
      located in the follicular cells and not in the oocyte. Many aspects of follicular
      cell physiology in Xenopus laevis, and other species, are regulated by hormones
      and neurotransmitters, including FSH and ACh. The follicular Cl- currents
      described in this paper may play an important role in the follicular cell-oocyte
      development.

PMID- 8301260
TI  - Slow inactivation of L-type calcium current distorts the measurement of L- and T
      type calcium current in Purkinje myocytes.
AB  - We have examined slow inactivation of L-type calcium current in canine Purkinje
      myocytes with the whole cell patch clamp technique. Slow inactivation is voltage
      dependent. It is negligible at -50 mV but can inactivate more than half of
      available iCaL at -10 mV. There are two major consequences of this slow
      inactivation. First, standard protocols for the measurement of T-type current can
      dramatically overestimate its contribution to total calcium current, and second,
      the position and steepness of the inactivation versus voltage curve for iCaL will
      depend on the method of measurement. Given the widespread attempts to identify
      calcium current components and characterize them biophysically, an important
      first step should be to determine the extent of slow inactivation of calcium
      current in each preparation.

PMID- 8301261
TI  - On the mechanism of rectification of the isoproterenol-activated chloride current
      in guinea-pig ventricular myocytes.
AB  - The whole cell configuration of the patch clamp technique was used to investigate
      the mechanism underlying rectification of the isoproterenol-activated chloride
      (Cl-) current in isolated guinea pig ventricular myocytes. When extracellular Cl-
      was replaced with either bromide (Br-), glutamate (Glut), iodide (I-),
      isethionate (Iseth), or nitrate (NO3-), the magnitude of the shift in reversal
      potential of the macroscopic current suggested the following selectivity
      sequence: NO3- > Br- > or = Cl- > or = I- > Iseth > or = Glut. This information
      was used to investigate the role of permeant ions in rectification of this
      current. Consistent with previous observations, when the concentration of
      intracellular Cl- (Cli-) was less than the concentration of extracellular Cl-
      (Clo-) (40 mM Cli-/150 mM Clo-) the current exhibited outward rectification, but
      when Cli- was increased to equal that outside (150 Cli-/150 Clo-), the current no
      longer rectified. Rectification in the presence of asymmetrical concentrations of
      permeant ions on either side of the membrane is predicted by constant field
      theory, as described by the Goldman-Hodgkin-Katz current equation. However, when
      the Cl- gradient was reversed (150 Cli-/40 Clo-) the current did not rectify in
      the opposite direction, and in the presence of lower symmetrical concentrations
      of Cl- inside and out (40 Cli-/40 Clo-), outward rectification did not disappear.
      Reducing Cli- by equimolar replacement with glutamate caused a concentration
      dependent increase in the degree of rectification. However, when Cli- was
      replaced with more permeant anions (NO3- and Br-), rectification was not
      observed. These results can be explained by a single binding site model based on
      Eyring rate theory, indicating that rectification is a function of the
      concentration and the permeability of the anions in the intracellular solution.

PMID- 8301263
TI  - Odorant-regulated Ca2+ gradients in rat olfactory neurons.
AB  - Olfactory neurons respond to odors with a change in conductance that mediates an
      influx of cations including Ca2+. The concomitant increase in [Cai] has been
      postulated to play a role in the adaptation to maintained odorant stimulation
      (Kurahashi, T., and T. Shibuya. 1990. Brain Research. 515:261-268. Kramer, R. H.,
      and S. A. Siegelbaum. 1992. Neuron. 9:897-906. Zufall, F., G. M. Shepherd, and S.
      Firestein. 1991. Proceedings of the Royal Society of London, B. 246:225-230.) We
      have imaged the distribution of [Cai] in rat olfactory neurons (RON) using the
      Ca2+ indicator fura-2. A large percentage of the RON (42%, n = 35) responded to
      odorants with an increase in [Cai]. About half of the responding neurons
      displayed an increase in [Cai] at the apical end of the cell, but not at the
      soma. Moreover, in those cells that responded to odors with a standing [Cai]
      gradient, the gradient could be maintained for long periods of time (minutes)
      provided that the cells were continuously stimulated. In contrast, K(+)-induced
      depolarization elicited a more homogeneous increase in [Cai]. The spatially
      inhomogeneous increase in [Cai] elicited by odorants in some cells has important
      implications for the role of Ca2+ in adaptation because channels and enzymes
      regulated by Ca2+ will be affected differently depending on their location.

PMID- 8301262
TI  - Role of facilitative glucose transporters in diffusional water permeability
      through J774 cells.
AB  - We have reported previously that in the presence of an osmotic gradient,
      facilitative glucose transporters (GLUTs) act as a transmembrane pathway for
      water flow. Here, we find evidence that they also allow water passage in the
      absence of an osmotic gradient. We applied the linear diffusion technique to
      measure the diffusional permeability (Pd) of tritiated water (3H-H2O) through
      plasma membranes of J774 murine macrophage-like cells. Untreated cells had a Pd
      of 30.9 +/- 1.8 microns/s; the inhibitors of facilitative glucose transport
      cytochalasin B (10 microM) and phloretin (20 microM) reduced that value to 15.3
      +/- 1.8 (50%) and 11.0 +/- 0.7 (62%) microns/s, respectively. In contrast, no
      significant effect on Pd was observed in cells treated with dihydrocytochalasin B
      (Pd = 28.4 +/- 1.5 microns/s). PCMBS (3 mM) inhibited glucose uptake by greater
      than 95%, and 3H-H2O diffusion by approximately 30% (Pd = 22.9 +/- 1.5
      microns/s). The combination of cytochalasin B plus pCMBS reduced Pd by about 87%
      (Pd = 3.9 +/- 0.3 microns/s). Moreover, 1 mM pCMBS did not affect the osmotic
      water permeability in Xenopus laevis oocytes expressing the brain/erythroid form
      of facilitative glucose transporters (GLUT1). These results indicate for the
      first time that about half of the total Pd of J774 cells may be accounted for by
      water passage across GLUTs. Hence, they highlight the multifunctional properties
      of these transporters serving as conduits for both water and glucose. Our results
      also suggest for the first time that pCMBS blocks glucose transport without
      affecting water permeation through GLUTs. Lastly, because pCMBS decreases the Pd
      of J774 cells, this suggests the presence in their plasma membranes of another
      protein(s) exhibiting water channel properties.

PMID- 8301264
TI  - Gating characteristics of a steeply voltage-dependent gap junction channel in rat
      Schwann cells.
AB  - The gating properties of macroscopic and microscopic gap junctional currents were
      compared by applying the dual whole cell patch clamp technique to pairs of
      neonatal rat Schwann cells. In response to transjunctional voltage pulses (Vj),
      macroscopic gap junctional currents decayed exponentially with time constants
      ranging from < 1 to < 10 s before reaching steady-state levels. The relationship
      between normalized steady-state junctional conductance (Gss) and (Vj) was well
      described by a Boltzmann relationship with e-fold decay per 10.4 mV, representing
      an equivalent gating charge of 2.4. At Vj > 60 mV, Gss was virtually zero, a
      property that is unique among the gap junctions characterized to date.
      Determination of opening and closing rate constants for this process indicated
      that the voltage dependence of macroscopic conductance was governed predominantly
      by the closing rate constant. In 78% of the experiments, a single population of
      unitary junctional currents was detected corresponding to an unitary channel
      conductance of approximately 40 pS. The presence of only a limited number of
      junctional channels with identical unitary conductances made it possible to
      analyze their kinetics at the single channel level. Gating at the single channel
      level was further studied using a stochastic model to determine the open
      probability (Po) of individual channels in a multiple channel preparation. Po
      decreased with increasing Vj following a Boltzmann relationship similar to that
      describing the macroscopic Gss voltage dependence. These results indicate that,
      for Vj of a single polarity, the gating of the 40 pS gap junction channels
      expressed by Schwann cells can be described by a first order kinetic model of
      channel transitions between open and closed states.

PMID- 8301265
TI  - Influences of neurotrophins on mammalian motoneurons in vivo.
AB  - Several recently reported investigations have shown that a member of the
      neurotrophin family of neuronal growth factors, brain-derived neurotrophic factor
      (BDNF), supports motoneurons in vitro and rescues motoneurons from naturally
      occurring and axotomy-induced cell death (Oppenheim et al., 1992b; Sendtner et
      al., 1992b; Yan et al., 1992; Koliatsos et al., 1993; Henderson et al., 1993). In
      the current study, we have explored the issue of whether BDNF and other
      neurotrophins act to regulate motoneuron survival during development and asked
      whether synthesis of motoneuron transmitter enzymes is also regulated. We first
      examined whether spinal motoneurons in newborn animals could retrogradely
      transport iodinated neurotrophins from their targets in a specific, receptor
      mediated manner. We found that motoneurons readily transported NGF, BDNF, and
      neurotrophin-3 (NT-3). The retrograde transport of one factor could be completely
      or largely blocked by excess of unlabeled homologous factor, but only partially
      blocked by excess of unlabeled heterologous factors. Since previous studies have
      shown that these three neurotrophins bind to the low-affinity NGF receptor,
      p75NGFR, with similar affinity, our data suggest that the retrograde transport of
      neurotrophins by motoneurons may be mediated by additional components, such as
      the trk family of proto-oncogenes. Consistent with this hypothesis, we
      demonstrate here that motoneurons express mRNA for two members of the trk family,
      trkB and trkC. Furthermore, both trkB and trkC were expressed by E13, consistent
      with a role for BDNF and NT-3 in regulating important developmental events
      involving motoneurons such as naturally occurring cell death. In order to
      determine which members of the neurotrophin family influence motoneuron survival
      and to assess the generality of their effects, we evaluated the abilities of NGF,
      BDNF, and NT-3 to save both spinal and cranial motoneurons after neonatal
      axotomy. Locally applied BDNF saved 40-70% of motoneurons which would ordinarily
      die after axotomy in lumbar and cranial motor pools, depending on the treatment
      protocol employed. NT-3 also exhibited some ability to rescue motoneurons and
      saved 20-25% of motoneurons which would die in the absence of treatment. Finally,
      we asked whether neurotrophins could influence synthesis of transmitter enzymes
      by motoneurons as well as their survival after axotomy. Locally applied BDNF and
      NT-3 could partially prevent the decrease of protein contents in L4 and L5
      ventral roots which normally follows sciatic nerve transection. However,
      treatment with these neurotrophins did not prevent the decrease in choline
      acetyltransferase (ChAT) activity in L4 and L5 ventral roots which results from
      this procedure.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8301266
TI  - Insulin-like growth factors: putative muscle-derived trophic agents that promote
      motoneuron survival.
AB  - Treatment of chick embryos in ovo with IGF-I during the period of normal,
      developmentally regulated neuronal death (embryonic days 5-10) resulted in a dose
      dependent rescue of a significant number of lumbar motoneurons from degeneration
      and death. IGF-II and two variants of IGF-I with reduced affinity for IGF binding
      proteins, des(1-3) IGF-I and long R3 IGF-I, also elicited enhanced survival of
      motoneurons equal to that seen in IGF-I-treated embryos. IGF-I did not enhance
      mitogenic activity in motoneuronal populations when applied to embryos during the
      period of normal neuronal proliferation (E2-5). Treatment of embryos with IGF-I
      also reduced two types of injury-induced neuronal death. Following either
      deafferentation or axotomy, treatment of embryos with IGF-I rescued approximately
      75% and 50%, respectively, of the motoneurons that die in control embryos as a
      result of these procedures. Consistent with the survival-promoting activity on
      motoneurons in ovo, IGF-I, -II, and des(1-3) IGF-I elevated choline
      acetyltransferase activity in embryonic rat spinal cord cultures, with des(1-3)
      IGF-I demonstrating 2.5 times greater potency than did IGF-I. A single addition
      of IGF-I at culture initiation resulted in the maintenance of 80% of the initial
      ChAT activity for up to 5 days, during which time ChAT activity in untreated
      control cultures fell to 9%. In summary, these results demonstrate clear
      motoneuronal trophic activity for the IGFs. These findings, together with
      previous reports that IGFs are synthesized in muscle and may participate in
      motoneuron axonal regeneration and sprouting, indicate that these growth factors
      may have an important role in motoneuron development, maintenance, and recovery
      from injury.

PMID- 8301267
TI  - Changing synaptic specificities in the nervous system of Caenorhabditis elegans:
      differentiation of the DD motoneurons.
AB  - During postembryonic development, the DD motoneurons in the nematode
      Caenorhabditis elegans completely reorganize their pattern of synapses. Ablation
      of a pair of embryonic precursors results in the absence of this entire class of
      motoneurons. In their absence animals exhibit two developmentally distinct
      locomotory defects. The transition period from one defect to the other is
      correlated with the synaptic reorganization of the DD mns. Mutations in a gene
      (unc-123) have been isolated that exhibit locomotory defects similar to those of
      the ablated adult animals. Genetic and cellular analyses of one of these alleles
      suggest that the unc-123 gene product may be involved in the reestablishment of
      functional synapses in these neurons.

PMID- 8301268
TI  - Calcium channels and GABA receptors in the early embryonic chick retina.
AB  - The properties of calcium channels were studied at the period of neurogenesis in
      the early embryonic chick retina. The whole neural retina was isolated from
      embryonic day 3 (E3) chick and loaded with a Ca(2+)-sensitive fluorescent dye
      (Fura-2). The retinal cells were depolarized by puff application of high-K+
      solutions. Increases in intracellular Ca2+ concentrations were evoked by the
      depolarization through calcium channels. The type of calcium channel was
      identified as L-type by the sensitivity to dihydropyridines. The Ca2+ response
      was completely blocked by 10 microM nifedipine, whereas it was remarkably
      enhanced by 5 microM Bay K 8644. Then we sought a factor to activate the calcium
      channel and found that GABA could activate it by membrane depolarization at the
      E3 chick retina. Puff application of 100 microM GABA raised intracellular Ca2+
      concentrations, and this Ca2+ response to GABA was also sensitive to the two
      dihydropyridines. Intracellular potential recordings verified clear
      depolarization by bath-applied 100 microM GABA. The Ca2+ response to GABA was
      mediated by GABAA receptors, since the GABA response was blocked by 10 microM
      bicuculline or 50 microM picrotoxin, and mimicked by muscimol but not by
      baclofen. Neither glutamate, kainate, nor glycine evoked any Ca2+ response. We
      conclude that L-type calcium channels and GABAA receptors are already expressed
      before differentiation of retinal cells and synapse formation in the chick
      retina. A possibility is proposed that GABA might act as a trophic factor by
      activating L-type calcium channels via GABAA receptors during the early period of
      retinal neurogenesis.

PMID- 8301269
TI  - Laryngeal muscle and motor neuron plasticity in Xenopus laevis: testicular
      masculinization of a developing neuromuscular system.
AB  - In Xenopus laevis, the sexual differentiation of the neuromuscular system
      responsible for courtship song is controlled by testicular androgen secretion. To
      explore the sensitivity of this system to androgenic stimulation, male and female
      frogs were gonadectomized and given testis transplants at seven different
      developmental stages between the end of metamorphosis and adulthood, grown to
      sexual maturity, and the laryngeal muscle fibers and motor axons were counted.
      Muscle fiber and axon numbers in males were not affected by the testicular
      transplant at any stage. In females, testicular transplants at all developmental
      stages increased muscle fiber numbers in adulthood. Values attained were,
      however, significantly less than those of adult intact or testis-transplanted
      males. Testis transplantation increased laryngeal axon numbers in females to
      levels equivalent to those of intact males; this effect was obtained at every
      stage of postmetamorphic development including adulthood. To further explore
      androgen regulation in adults, males and females were gonadectomized and
      implanted with silicone tubes containing testosterone propionate for 1.5-3 years
      and laryngeal muscle fibers and axon numbers compared to those of gonadectomized
      or sham-operated adult controls. Neither treatment with exogenous androgen nor
      gonadectomy had any effect on laryngeal muscle fiber or axon number in either
      males or females; values did not differ from those of sham-operated controls. We
      conclude that testicular secretions can induce laryngeal muscle fiber and axon
      addition in females throughout postmetamorphic life. This degree of plasticity,
      exhibited after the period when adult values are normally attained, stands in
      contrast to the effects of administration of synthetic androgen and suggests that
      the degree of plasticity in adult females may be underestimated if exogenous
      hormones rather than testicular transplants are provided.

PMID- 8301270
TI  - Neurotrophin-3 affects proliferation and differentiation of distinct neural crest
      cells and is present in the early neural tube of avian embryos.
AB  - Neurotrophin-3 is mitogenic for cultured quail neural crest cells (Kalcheim et
      al., 1992, Proc. Natl. Acad. Sci. USA 89:1661-1665). We now report that
      neurotrophin-3 also influences the survival and/or differentiation of a subset of
      postmitotic neural crest precursors into neurons, provided these progenitors are
      grown on a cellular substrate. When cultured for 1 day on monolayers of NT-3
      producing, chinese hamster ovary cells, 59% of the neural crest clusters growing
      on the transfected line revealed the presence of intense neuronal outgrowth,
      compared to 25% of that in controls. Moreover, dissociated neural crest cells
      grown for 20 h on top of mesodermal cells in the presence of various
      concentrations of purified recombinant neurotrophin-3 displayed a dose-dependent
      increase in neuronal number. Localization experiments using specific polyclonal
      antibodies, revealed that neurotrophin-3 is confined to neuroepithelial cells of
      quail neural tubes in situ on E2 and E3, and to E2 neural tubes grown in culture
      for 24 h. At this stage, neural crest cells and somites were negative. At later
      stages, staining was likewise apparent in peripheral nerves and dorsal root
      ganglia. We, therefore, propose that NT-3, a factor that is expressed in the
      early avian central nervous system, has multiple effects both on the
      proliferation and differentiation of distinct neural crest cells, which depend on
      the state of commitment of the responsive progenitors.

PMID- 8301271
TI  - Cell recognition during synaptogenesis is revealed after temperature-shock
      induced perturbations in the developing fly's optic lamina.
AB  - Houseflies (Musca domestica) were exposed to pulses of heat (1 h) or cold
      (several hours) during early pupal life, and the effects were investigated on the
      development of the first optic neuropile, or lamina, of the visual system. The
      treatments were designed to perturb the cellular organization of the cartridges,
      the unit synaptic structures of the lamina, so as to provide novel synaptic
      opportunities among the normally fixed composition of these modules, thereby
      testing the preferences of their component cells during synaptogenesis. Various
      abnormalities were identified, but these were not always consistent between
      flies: retinal abnormalities included the loss and fusion of rhabdomeres,
      especially of the central cells of the ommatidium, whereas in the lamina low
      frequencies of abnormal cartridges were found. These included seven that were
      studied with serial sections, which instead of the normal pair of L1 and L2
      monopolar interneurons had supernumerary cells of this type. The normal pairing
      of L1 and L2 at postsynaptic sites of receptor terminal tetrad synapses was
      preserved in these cases, the cells eschewing pairings of homologous L1/L2 or
      L2/L2 partners. This meant that more than one L1 could pair with a single L2 and
      vice versa, even at the same terminal, and appeared to do so opportunistically on
      the basis of proximity, with cells closer to each other pairing more frequently.
      Thus the cells behave during synaptogenesis as if they recognize other cells only
      as cell types (receptor, L1 or L2) and not as individual cells.

PMID- 8301272
TI  - Fracture of ceramic femoral heads in total hip arthroplasty.
AB  - Five cases of fractured ceramic heads occurring 1-2 years after primary hip
      arthroplasty are reported. All fractures occurred without significant trauma. As
      the mechanism of these failures has not been clarified, the authors have stopped
      using ceramic heads.

PMID- 8301273
TI  - Cementless hemispheric acetabular components. 2-4-year results.
AB  - A retrospective clinical and radiographic analysis was performed on 99 patients
      (106 hips) undergoing total hip arthroplasty with noncemented Harris-Galante
      (Zimmer, Warsaw, IN) or Optifix (Smith Nephew Richards, Memphis, TN) acetabular
      components. There were 94 primary and 12 revision procedures with a minimum
      follow-up period of 24 months (range, 24-52 months). The cups were evaluated for
      evidence of vertical and horizontal migration, as well as the presence of
      radiolucencies at the bone-implant interface. Age, sex, component inclination and
      medialization, cup coverage, and number of fixation screws used were examined to
      determine the influence of these factors on the incidence of cup migration or
      radiolucent line formation. A radiolucent line was present in at least one zone
      in 60% of the Harris-Galante and 45% of the Optifix cups. Progressive radiolucent
      lines were noted in two of the Optifix and three of the Harris-Galante
      components. Two Harris-Galante cups (1.9%) were revised. There were no Optifix
      cup migrations or evidence of instability in the Optifix or remaining Harris
      Galante cups. Although there was a trend toward an increased incidence of
      radiolucencies in those cups lacking complete coverage, no statistically
      significant radiographic predictors for failure or impending failure could be
      determined from this short-term follow-up study. With the exception of the two
      revisions, all acetabular components performed well clinically over the study
      period.

PMID- 8301274
TI  - Loosening of threaded acetabular components. Radiographic manifestations.
AB  - Radiographic signs of loosening were assessed, and their sequential appearance
      recorded, in a retrospective analysis of 20 loosened, threaded acetabular cups.
      There was radiographic evidence of loosening in 19 (95%) cups. In decreasing
      order of frequency, the radiographic manifestations included bone resorption
      between the threads in 19 (95%) cups, increased bone density above the cup in 15
      (75%), continuous lucency around the cup in 14 (70%), axial migration in 9 (45%),
      and rotation in 6 (30%). The order of appearance of these radiographic
      manifestations was the same as the order of frequency of occurrence of the
      alterations. In the one patient with no radiographically detectable signs of
      loosening, the cup did not move freely but was easily detached during surgery.
      Early radiographic diagnosis of loosening requires accurate positioning of the
      patient in order for the radiographs to reveal bone resorption between the
      threads of the cup.

PMID- 8301275
TI  - In vitro and in vivo studies of pressurization of femoral cement in total hip
      arthroplasty.
AB  - Improvements in cementing techniques in the absence of pressurization of the
      cement have led to major increases in the long-term success rate of fixation of
      the femoral components of cemented total hip arthroplasty (THA). The strength of
      the cement-bone interface is strongly related to cement intrusion into the bone.
      The depth of cement intrusion, in turn, is correlated with the cement-intrusion
      pressure. Thus, adding cement pressurization to those current techniques that
      have already been validated may further increase the long-term durability of
      fixation of the femoral component of cemented THA. To assess cement
      pressurization in the proximal femur for THA, the authors compared in vitro the
      efficacy of three existing pressurization systems (the Johnson and Johnson system
      [New Brunswick, NJ], the Miller system [Zimmer, Warsaw, IN], and the Zimmer
      system [Zimmer]) in cadaver femurs using pressure transducers and evaluated their
      ease and optimization for clinical use. The authors then selected one (the Zimmer
      system) for use in studies in vivo to quantify the actual pressures achieved in
      the medullary canal in vivo under surgical conditions using pressure transducers
      placed throughout the femoral cortex. Each of the three commercially available
      femoral cement pressurization systems has its own advantages and disadvantages.
      All three systems were shown to produce average peak cement-intrusion pressures
      in vitro of over 21 N/cm2 (30 psi) throughout the cement mantle including,
      importantly, in the proximal portion of the femur.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8301276
TI  - Posterior allograft bone-block for recurrent dislocation of the hip after
      hemiarthroplasty in noncompliant patients with neuromuscular disease.
AB  - Two mentally retarded patients with cerebral palsy developed recurrent
      dislocation of the hip after hemiarthroplasty. Instability had persisted despite
      release of contracted soft tissues, conversion to a bipolar arthroplasty, and
      cast immobilization in one patient and repeated closed reductions with abduction
      splinting and bed rest in the other. Both patients were treated with a posterior
      femoral head allograft bone-block that resulted in restoration of hip function
      and control of recurrent dislocations.

PMID- 8301277
TI  - Computer simulations of stress-related bone remodeling around noncemented
      acetabular components.
AB  - The authors have used computer modeling techniques to examine stress-related bone
      changes in the acetabular region. Using a previously developed theory for bone
      development and adaptation, the authors simulated the distribution of bone
      density in the natural pelvis as well as changes in bone density following total
      hip arthroplasty. The geometry of the finite element model was based on a two
      dimensional slice through the pelvis. Starting from a solid, homogeneous
      structure, the computer simulations predicted the distribution of bone density
      throughout the natural pelvis. The predicted bone density distribution in this
      first simulation agreed well with the actual bone density distribution only when
      loads representing multiple activities were incorporated. Using the predicted
      density distribution as a starting point the authors modified the finite element
      models to study two designs of noncemented, metal-backed acetabular cups. The
      simulations with fully fixed bone-implant interfaces predicted extensive loss of
      bone density medial and inferior to the prosthetic components. The simulations
      with loose interfaces led to more moderate losses of bone density, indicating a
      load transfer more similar to that which occurs in the natural joint. The
      differences in simulated bone remodeling between the two component designs were
      quite minimal. These results indicate that acetabular components with full bony
      ingrowth may induce significant stress-related bone remodeling due to a
      nonphysiologic transfer of load.

PMID- 8301278
TI  - Nonsteroidal antiinflammatory drugs, perioperative blood loss, and transfusion
      requirements in elective hip arthroplasty.
AB  - A study of 160 elective total hip arthroplasties revealed that those patients
      receiving nonsteroidal antiinflammatory drugs (NSAIDs) in the preoperative period
      had a significantly increased perioperative blood loss and transfusion
      requirement when compared with a control group receiving other forms of analgesia
      for their osteoarthritis. The results suggest that NSAIDs are implicated in
      increasing the operative blood loss in these patients. The range of increased
      blood loss varied from 1.57 to 2.08 times the blood loss in the control group,
      and this effect was seen when the operation was carried out under spinal as well
      as when under general anesthesia.

PMID- 8301279
TI  - Bone scan, gallium scan, and hip aspiration in the diagnosis of infected total
      hip arthroplasty.
AB  - The difficulty in differentiating aseptic loosening from infection in painful
      total hip arthroplasty is well recognized. This prompted a review of the efficacy
      of the preoperative investigations used at the authors' institution. One hundred
      forty-four patients who underwent revision hip arthroplasty were reviewed.
      Seventy-two had sequential bone-gallium scan, and/or hip aspiration, and
      intraoperative Gram stain. These were compared to intraoperative culture as the
      gold standard. Twenty infected hips were detected on culture. For prediction of
      infection, the bone-gallium scan had a sensitivity of 38% and a specificity of
      100%. Hip aspiration had a sensitivity of 57% and a specificity of 97%. The
      investigations combined gave a sensitivity of 64% and a specificity of 95%.
      Intraoperative Gram stain compared with subsequent culture yielded a sensitivity
      of 23% and a specificity of 100%. Uncemented hips were infected more frequently
      (47%) than cemented hips (9%), significant at P < .0001. It was concluded that
      bone-gallium imaging is not an effective method for investigating painful hip
      prostheses for sepsis and offers no additional advantage over hip aspiration.
      Intraoperative Gram stain also missed a large number of infections. Other
      modalities, such as indium-labeled-leukocyte imaging and capsular histologic
      examination, may be more efficacious. A significant difference in the number of
      infections found in cemented versus uncemented hips was shown, hence greater
      vigilance for infection is required when patients present with painful uncemented
      hip arthroplasties.

PMID- 8301280
TI  - A qualitative and quantitative study of retrieved femoral heads in three
      different types of resurface hip arthroplasties.
AB  - Tissue reactions and percentage of mineralized bone in three different types of
      retrieved femoral head hip resurface prostheses were studied in undecalcified
      ground sections without removing the metal. All of the prostheses demonstrated
      soft tissue between the cement-implant and bone. There were some areas without
      soft tissue between bone and cement. This bone was often not normally stained,
      indicating a disturbed mineralization. The soft tissue layer in the cemented
      prostheses was observed in different stages of necrosis, while the uncemented
      prostheses demonstrated a thick collagen membrane. One of the cemented groups
      demonstrated a gradual decrease of mineralized bone towards the cement. The
      uncemented implants revealed normal bone qualitatively and quantitatively when
      the bone bordering the prosthesis was excluded. Too high interfacial stresses
      were probably a major failure mechanism, especially in the rapidly failed
      noncemented prostheses. Negative long-term effects of the cement on the bone may
      have contributed to failure in the cemented resurface arthroplasties.

PMID- 8301281
TI  - Muscle strength following total hip arthroplasty. A comparison of trochanteric
      osteotomy and the direct lateral approach.
AB  - Twenty-seven patients who had hip arthroplasty operated on with trochanteric
      osteotomy were compared with 54 patients when the direct lateral approach was
      used. The strength of the hip abductors, adductors, extensors, and flexors were
      measured at least 2 years following surgery. The strength of these muscle groups
      recovered to the same level as those on the nonoperated side, and there was no
      significant difference between the two groups of patients. Functionally, the
      direct lateral approach is a safe alternative to trochanteric osteotomy.

PMID- 8301282
TI  - Trochanteric osteotomy for recurrent dislocation of total hip arthroplasty.
AB  - Twenty-one patients with recurrent dislocation of total hip arthroplasty were
      treated by trochanteric osteotomy and distal advancement of the greater
      trochanter. There were no malpositioned prostheses. In 17 patients no further
      dislocations occurred. One patient, who had the hip arthroplasty in a paretic
      leg, continued to dislocate after the osteotomy and the prosthetic components
      were removed 5 months after surgery. The remaining three patients became stable
      after further surgery: cup augmentation in one and reattachment of the greater
      trochanter in two. Advancement of the greater trochanter is recommended in
      patients with recurrent dislocation of their total hip arthroplasty when no
      apparent malposition of the prosthetic components can be identified.

PMID- 8301283
TI  - Dislocation following primary posterior-stabilized total knee arthroplasty.
AB  - From 1981 through 1991, 3,032 primary total knee arthroplasties were performed
      using the Insall-Burstein Posterior Stabilized Condylar Prosthesis (IB-I, IB-II,
      and IB-II modified) (Zimmer, Warsaw, IN). Fifteen posterior dislocations
      occurred: 4 with the IB-I system occurring 2 or more years after surgery, 10 with
      the IB-II system (8 occurring 6 months after surgery and 2 occurring 2-3 years
      after surgery), and 1 with the IB-II modified system occurring 9 months after
      surgery. Statistically significant differences for the rate of dislocation
      between both the IB-I and IB-II modified arthroplasties versus the IB-II
      arthroplasties were found (P < .001). In an attempt to identify a cause for these
      dislocations, the authors retrospectively assessed the 15 dislocated cases with
      respect to sex, age, weight, height, preoperative and postoperative Hospital for
      Special Surgery scores, preoperative and postoperative alignment, preoperative
      versus postoperative reconstruction dimensions, patellar thickness and height,
      and postoperative flexion and compared the results with those patients who did
      not experience dislocation. Possible etiologies and mechanisms of dislocation
      were sought. There were no significant differences between the control and study
      groups for any variable assessed, with the exception of postoperative flexion,
      which averaged 118 degrees for the study group and 105 degrees for the control
      group (P < .001). Conservative management was successful in 11 cases. In
      September 1988 the IB-II system was introduced; modification of the tibial insert
      was made in January 1990.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301284
TI  - Femoral neck bone density. Direct measurement and histomorphometric validation.
AB  - The purpose of this study was to develop a method for directly measuring bone
      density of femoral neck sections. Three types of density were measured. Real
      density equals wet weight divided by the actual volume of bone tissue (real
      volume). Apparent density equals wet weight divided by the total volume occupied
      by the bone plus the pore spaces (total sample volume). Ash density equals the
      ash weight divided by the real volume. Corticocancellous cross-sections of the
      femoral neck were analyzed for density at two levels: level 1, proximal neck and
      level 3, distal neck. Density measurements were compared with histomorphometric
      measurements performed on cross-sections at the midportion of the femoral neck
      (level 2) and with a clinical radiographic measure of bone density (cortical
      index 3 cm below the lesser trochanter). No correlation was found between
      apparent density and either real (r = .12, P = .62) or ash density (r = -.09, P =
      .72) within a given femoral neck section. There was, however, a strong
      correlation between real and ash density (r = .93, P = .0001). This was expected
      because real and ash densities are both reflections of bone mineralization.
      Apparent density showed better correlation, when comparing level 1 with level 3
      sections (r = .76, P = .0001), than did ash (r = .57, P = .01) or real density (r
      = .55, P = .01). There was no correlation between either real or ash density with
      any histomorphometric parameter. Apparent density was moderately correlated with
      total bone area expressed as a percentage of cross-sectional area (r = .66, P =
      .008). This finding tends to validate the direct measurement of apparent density
      in that both apparent density and total bone area are measurements of the
      concentration of bone in space. No significant correlation was found between any
      of the density measurements and the cortical index at 3 cm. This underscores the
      necessity for precisely qualifying any definition or discussion of bone quality.
      The success or failure of hip implants may be at least partially determined by
      the ability of the bone to withstand the insult of implantation of the prosthesis
      and to adapt successfully to the new mechanical environment. This study
      represents an early phase of defining parameters that may have prognostic value
      in long-term implant fixation.

PMID- 8301285
TI  - Disassembly of a modular humeral prosthesis. A case report.
AB  - A modular humeral hemiarthroplasty utilizing a prosthesis with a taper-lock
      design was performed on a 77-year-old woman with a diagnosis of rotator cuff
      arthropathy. Radiographic examination at 3 months after surgery revealed
      disarticulation of the modular head and neck from the humeral prosthetic stem.
      This is a case report of a disarticulated modular humeral hemiarthroplasty.

PMID- 8301286
TI  - Cystic enlargement of the iliopsoas bursa causing venous obstruction as a
      complication of total hip arthroplasty. A case report.
AB  - The authors report an unusual complication of total hip arthroplasty. A patient
      developed significant swelling and discomfort in the left lower extremity 4 1/2
      years following a left total hip arthroplasty. Magnetic resonance imaging and
      venography demonstrated a large intrapelvic mass compressing the external iliac
      vein. An arthrogram revealed a cystic cavity consistent with an iliopsoas bursa
      in communication with the hip pseudocapsule. Two aspirations of the bursa led to
      resolution of the cystic enlargement and symptoms. An enlarged iliopsoas bursa
      should be considered in the differential diagnosis of hip pain or extremity
      swelling after total hip arthroplasty.

PMID- 8301287
TI  - Abnormal movement related potentials in patients with lesions of basal ganglia
      and anterior thalamus.
AB  - Movement-related cortical potentials (MRCPs) were recorded from scalp electrodes
      during wrist flexion in 15 dystonic patients with bilateral (nine) or unilateral
      (six) circumscribed lesions in the striatum (eight), pallidum (six), or anterior
      thalamus (one). The results were compared with those of 10 age-matched healthy
      volunteers. The early (BP) and late (NS') MRCP components were assessed in terms
      of their gradients and distribution on the scalp in Cz, C3', and C4'. The
      gradients of both BP and NS' components were significantly flatter in the
      patients with bilateral lesions than in the control subjects. Also, the BP
      gradient was maximum at Cz, and the NS' component was contralaterally predominant
      in the control subjects but not in the patients. In patients with unilateral
      lesions, the gradients were flatter (p < 0.05) during movement of the dystonic
      wrist than during movement of the normal wrist. This difference was significant
      for BP and NS', regardless of the location of the electrodes. Also, the normal
      topographic predominance of BP at Cz and of contralateral NS' disappeared. The BP
      and NS' components of the MRCPs are thought to reflect preparatory activity in
      the supplementary motor area and the primary motor cortex before movement.
      Reduced BP and NS' gradients in patients with both bilateral and unilateral
      lesions of the basal ganglia, which project towards the supplementary motor area,
      are consistent with this hypothesis. The bilateral nature of these reductions
      suggests that both the ipsilateral and the contralateral motor cortex are
      involved in the genesis of the MRCPs and that the dystonia in these patients is
      associated with impaired motor preparation.

PMID- 8301288
TI  - Acute diffuse leukoencephalitis in HIV-1 infection.
AB  - The clinical, neuroradiological, and cerebrospinal fluid findings of a case with
      acute diffuse leukoencephalitis, a demyelinating disease associated with human
      immunodeficiency virus infection of the brain, is reported. The patient presented
      with acute tetraparesis as the primary manifestation of a previously symptom free
      HIV infection. Cerebrospinal fluid analysis showed enhanced inflammatory
      abnormalities with high concentrations of P24 antigen. MRI showed diffuse white
      matter hyper-intensities in both hemispheres. In the follow up over 22 months,
      the neurological deficits disappeared after antiretroviral treatment in good
      correlation with improvements in MRI as well as in inflammatory cerebrospinal
      fluid abnormalities.

PMID- 8301289
TI  - Excitability of the motor cortex to magnetic stimulation in patients with
      cerebellar lesions.
AB  - The excitability of the motor cortex to magnetic stimulation was evaluated in
      seven patients with cerebellar lesions (six patients with a unilateral lesion)
      and in 20 control subjects. Magnetic motor threshold was defined at rest. In all
      but one of the patients with a hemicerebellar lesion the threshold was higher in
      the motor cortex contralateral to the impaired hemicerebellum and the right/left
      threshold asymmetry was clearly greater than normal. In the patient with a lesion
      involving both cerebellar hemispheres the magnetic threshold was above the normal
      limit on both sides. The latencies of motor responses were normal in all
      patients. This increase in the magnetic threshold of the motor cortex
      functionally related to the impaired hemicerebellum suggests the existence of a
      facilitating tonic action of the cerebellum on central motor circuits that might
      act at the cortical, or spinal level, or both.

PMID- 8301290
TI  - Progressive paraparesis, lymphocytic meningitis, and stroke in a 37-year-old man.

PMID- 8301291
TI  - Unilateral asterixis due to a lesion of the ventrolateral thalamus.
AB  - A case of unilateral asterixis in a man with a focal ischaemic lesion of the
      contralateral ventral thalamus is presented. Atypically, the movements were
      present at rest and had a pattern of activation that resulted in an initial
      misdiagnosis of epilepsia partialis continua. This case emphasises the importance
      of electromyographic analysis in establishing the correct diagnosis of
      involuntary movements before starting specific treatment.

PMID- 8301292
TI  - Acute dystonia due to clozapine.

PMID- 8301293
TI  - Changes in CSF amino acid concentrations during the evolution of amyotrophic
      lateral sclerosis.

PMID- 8301294
TI  - Selective enhancement of executive function by idazoxan in a patient with
      dementia of the frontal lobe type.

PMID- 8301295
TI  - Ictal language shift in a polyglot.

PMID- 8301296
TI  - Relief of trigeminal neuralgia by proparacaine.

PMID- 8301297
TI  - Soluble interleukin-2 receptor levels in serum of patients with demyelinating
      polyneuropathy associated with monoclonal gammopathy.

PMID- 8301298
TI  - Mechanisms of cerebral artery thrombosis: a histopathological analysis on eight
      necropsy cases.
AB  - The mechanisms of thrombus formation in atherosclerotic cerebral arteries are
      still controversial, although intraplaque haemorrhage and rupture of the
      atheromatous plaques have been proposed. A histopathological analysis of segments
      of the thrombosed large intracranial arteries was carried out on eight patients
      who died within 28 days after brain infarction. The study revealed occlusive
      thrombi in six and mural thrombi in two, developing mostly at the site of
      greatest stenosis or just distal to it. The histological characteristics of the
      thrombosed arteries were plaque rupture in three, intramural haemorrhage in one,
      ulceration in one, and thrombosis in the absence of plaque rupture or intramural
      haemorrhage in three. Occlusive emboli distal to the site of cerebral artery
      thrombosis (intracranial artery-to-artery thromboembolism) were observed in two.
      The following conclusions were drawn from the study: 1) plaque rupture or
      intraplaque haemorrhage is not a sine qua non for cerebral artery thrombosis; 2)
      occlusions occur at the site of greatest luminal compromise or just distal to it,
      and 3) non-occlusive mural thrombosis can occur in the absence of plaque rupture
      and eventually lead to local occlusion or distal embolisation.

PMID- 8301299
TI  - Casper Wistar (1760-1818).

PMID- 8301300
TI  - Measuring ataxia: quantification based on the standard neurological examination.
AB  - To quantify ataxia in a simple way four tests were developed and analysed, based
      on the neurological examination: a tapping test for the arms (test 1), another
      one for the legs (test 2), a quantified finger-to-nose test (test 3), and a
      modified Romberg test (test 4). All tests were performed by 115 volunteers, 13
      patients with cerebellar ataxia and 25 patients with sensory ataxia due to
      neuropathy. The test-retest repeatability was excellent. Tests 1, 2 and 4 were
      age-dependent, with lower scores above age 65. On test 1, 2 and 4 both groups of
      patients performed worse than controls; the correlation with the ataxia scale of
      Nobile-Orazio and the modified disability Rankin scale was good (P < 0.05).
      Although test 3 could differentiate between sensory and cerebellar ataxia, it was
      not useful for quantifying the degree of ataxia. To determine the practical value
      of the four tests, 11 patients performed the tests for a second time after a
      follow up period of 16 months. The results indicate that tests 1, 2 and 4 are
      sensitive for the detection of ataxia and of changes in its severity.

PMID- 8301301
TI  - Pure amnesia after unilateral left polar thalamic infarct: topographic and
      sequential neuropsychological and metabolic (PET) correlations.
AB  - A 54-year-old patient who had an isolated small polar thalamic infarct and acute
      global amnesia with slight frontal type dysfunction but without other
      neurological dysfunction was studied. Memory improved partially within 8 months.
      At all stages the impairment was more severe for verbal than non-verbal memory.
      Autobiographic recollections and newly acquired information tended to be
      disorganised with respect to temporal order. Procedural memory was unaffected.
      Both emotional involvement and pleasure in reading were lost. On MRI, the infarct
      was limited to the left anterior thalamic nuclei and the adjacent mamillothalamic
      tract. The regional cerebral metabolic rate of glucose (measured with PET) was
      decreased on the left in the thalamus, amygdala, and posterior cingulate cortex 2
      weeks after the infarct, and in the thalamus and posterior cingulate cortex 9
      months later. These findings stress the specific role of the left anterior
      thalamic region in memory and confirm that longlasting amnesia from a thalamic
      lesion can occur without significant structural damage to the dorsomedial
      nucleus. Furthermore, they suggest that the anterior thalamic nuclei and possibly
      their connections with the posterior cingulate cortex play a role in emotional
      involvement linked to ipsilateral hemispheric functions.

PMID- 8301302
TI  - Immunotherapy for multiple sclerosis.

PMID- 8301303
TI  - Limb temperature and human tremors.
AB  - The changes in postural tremor of the hand produced by moderate cooling of the
      muscles of one forearm have been investigated in 16 normal subjects and in 16
      patients with essential tremor. In both groups, cooling produced a profound long
      lasting decrease in tremor level of the ipsilateral hand. In normal subjects,
      although cooling reduced the tremor size, the EMG of the active muscle clearly
      increased. Warming the limb in normal subjects produced an increase in tremor
      level and decrease in EMG. Cooling or warming the limb did not, however,
      significantly change the peak frequency which was quite stable for each subject.
      The results of cooling were compared with a brief period of ischaemia, which also
      reduces tremor size. Local cooling may be a useful manoeuvre for patients with
      essential tremor, and for others who wish to reduce their tremor temporarily in
      order to improve dexterity.

PMID- 8301304
TI  - Pathophysiology of hemimasticatory spasm.
AB  - Two patients aged 21 and 50 years presented with facial hemiatrophy and
      unilateral spasms of the masticatory muscles. Masticatory muscle biopsy showed
      normal findings in both patients and facial skin biopsy specimens only showed
      atrophy, although morphoea (localised facial scleroderma) had been diagnosed nine
      years previously in the second patient. The involuntary movements consisted of
      brief twitches and prolonged contractions clinically and electromyographically
      similar to those of hemifacial spasm and cramps. The jaw jerk and the silent
      periods were absent in the affected muscles. Direct stimulation of the muscle
      nerve and transcranial stimulation of the trigeminal root demonstrated slowing of
      conduction and after-activity due to autoexcitation. Observations in other
      reported cases and these two patients suggest that hemimasticatory spasm is
      produced by ectopic activity secondary to focal demyelination of the trigeminal
      motor nerve fibres. The proposed cause of the neuropathy is focal damage to the
      masticatory nerves caused by compression, possibly resulting from the deep tissue
      changes that occur in facial hemiatrophy.

PMID- 8301305
TI  - Magnetic resonance imaging in degenerative ataxic disorders.
AB  - MRI of the brain was performed in 53 patients with a variety of degenerative
      ataxias and related disorders and 96 control subjects. Atrophy of intracranial
      structures was not seen in patients with the pure type of hereditary spastic
      paraplegia, or in early cases of Friedreich's ataxia. In advanced Friedreich's
      ataxia there was atrophy of the vermis and medulla. The MRI features of early
      onset cerebellar ataxia with retained reflexes were variable, and suggest
      heterogeneity. In autosomal dominant cerebellar ataxias, most patients had
      cerebellar and brainstem atrophy, probably reflecting the pathological process of
      olivopontocerebellar atrophy; there was no clearly defined group with both
      clinical and imaging features of isolated cerebellar involvement. The MRI
      abnormalities in idiopathic late onset cerebellar ataxia were predominantly those
      of cerebellar and brainstem atrophy or pure cerebellar atrophy. The clinical and
      imaging features of brainstem abnormalities were discordant in several patients.
      Pure cerebellar atrophy was associated with slower progression of disability.
      Cerebral atrophy was common in the late onset ataxias. Cerebral white matter
      lesions, although usually few in number, were observed in significantly more
      patients than controls, particularly those aged over 50 years.

PMID- 8301306
TI  - Utility of stereoelectroencephalography in preoperative assessment of temporal
      lobe epilepsy.
AB  - Of 269 consecutive patients entered into a preoperative assessment programme for
      possible surgical treatment of epilepsy, 33 had intracranial recording (SEEG)
      with combined subdural and depth electrodes for the purpose of localising a
      suspected temporal site of seizure onset. The findings in these patients are
      analysed with particular reference to: 1) the criteria of selection for SEEG and
      their validity; 2) information on SEEG compared with that obtained by less
      invasive means, including foramen ovale telemetry; 3) information on the use of
      intracerebral electrodes compared with subdural placements; 4) possible
      predictors of failure of localisation by SEEG and of surgical outcome. It was
      concluded that SEEG had usefully contributed to the management of 69% of the
      patients in whom it was used, establishing a previously unidentified site of
      seizure onset in 33%, correcting an erroneous localisation in 15%, and
      establishing inoperability in 21% of patients. No predictors of failure of SEEG
      or of surgery emerged; thus there was no evidence of unnecessary use of this
      procedure. Five patients were found with incorrect lateralisation of seizure
      onset on foramen ovale recording (of a total of 192 foramen ovale telemetries).
      Localisation of the ictal onset zone either by the distribution of inter-ictal
      discharges or by the initial ictal changes at subdural electrodes was unreliable,
      confirming the need for ictal, depth recordings.

PMID- 8301307
TI  - Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid
      cisternal cerebrospinal fluid.
AB  - Endothelin (ET) is considered one of the most potent vasoconstrictor
      polypeptides; several experimental studies have suggested its possible role in
      the pathogenesis of arterial vasospasm after subarachnoid haemorrhage (SAH).
      Previously reported data on plasma and CSF levels of endothelin in patients with
      a diagnosis of SAH have been controversial. Cisternal endothelin CSF levels and
      the possibility that they could be related to vasospasm and other clinical
      patterns of SAH were investigated. CSF samples were obtained from 55 patients
      admitted after angiographic diagnosis of intracranial aneurysm. Levels of ET-1
      and ET-3 were measured through radio-immunoassay technique. Twelve patients who
      had operations for unruptured aneurysms were considered control cases; 43
      patients with SAH were classified according to: Hunt and Hess grading at
      admission, vasospasm grading, CT classification and timing of surgery. In all 55
      patients ET-1 was measured, while positive levels of ET-3 were found only in 17
      cases of 48. No linear correlation was found between cisternal CSF ET-1 levels
      when considering time of surgery, CT classification, Hunt and Hess grading at
      admission, and vasospasm grading. The results of ET-3 assay should be considered
      with great caution because of the low percentage of positive cases. Cisternal CSF
      levels of ET-1 and ET-3 are not directly related to the occurrence of arterial
      vasospasm after the aneurysm rupture, or to other major clinical patterns of SAH;
      however, ET-1 expression occurs either in paraphysiological (unruptured aneurysm)
      or in pathological conditions (SAH). It is suggested that ET may potentiate, or
      may be potentiated by, other factors playing a consistent pathophysiological role
      in the development of vasospasm.

PMID- 8301308
TI  - Clinical genetics in neurological disease.

PMID- 8301309
TI  - Selective deficit of visual size perception: two cases of hemimicropsia.
AB  - Hemimicropsia is a rare disorder of visual perception characterized by an
      apparent reduction of the size of objects when presented in one hemifield. We
      report two cases of hemimicropsia resulting from focal brain lesions. The first
      patient was an art teacher and could accurately depict his abnormal visual
      perception. He subsequently died and his brain was examined post mortem. In the
      second patient, micropsia was assessed by a quantified size comparison task. The
      size of a given object is normally perceived as constant across any spatial
      position. Hemimicropsia may thus be considered a limited violation of the size
      constancy principle. Behavioural and anatomical data are discussed in relation to
      the neural basis of visual object perception in humans.

PMID- 8301310
TI  - Cognitive deficits in progressive supranuclear palsy, Parkinson's disease, and
      multiple system atrophy in tests sensitive to frontal lobe dysfunction.
AB  - Groups of patients with idiopathic Parkinson's disease, multiple system atrophy,
      and progressive supranuclear palsy or Steele-Richardson-Olszewski syndrome,
      matched for overall clinical disability, were compared using three computerised
      cognitive tests previously shown to be sensitive to frontal lobe dysfunction. On
      a test of planning based on the Tower of London task, all three groups were
      impaired, but in different ways. The groups with palsy and Parkinson's disease
      were slower in the measure of initial thinking time, whereas the group with
      multiple system atrophy was only slower in a measure of thinking time subsequent
      to the first move, resembling patients with frontal lobe damage. On a test of
      spatial working memory, each group showed deficits relative to their matched
      control groups, but the three groups differed in their strategy for dealing with
      this task. On a test of attentional set shifting, each group was again impaired,
      mainly at the extradimensional shifting stage, but the group with Steele
      Richardson-Olszewski syndrome exhibited the greatest deficit. The results are
      compared with previous findings in patients with Alzheimer's disease or frontal
      lobe damage. It is concluded that these basal ganglia disorders share a
      distinctive pattern of cognitive deficits on tests of frontal lobe dysfunction,
      but there are differences in the exact nature of the impairments, in comparison
      not only with frontal lobe damage but also with one another.

PMID- 8301311
TI  - Unilateral spatial neglect due to right frontal lobe haematoma.
AB  - Two patients with unilateral spatial neglect caused by right frontal lobe lesions
      underwent cerebral blood flow studies. A 54-year-old, right-handed woman
      developed left hemiplegia and frontal lobe neglect associated with cerebral
      haemorrhage after surgical excision of a frontal tumour. A 66-year-old, right
      handed woman developed a haemorrhage in the right frontal lobe caused by rupture
      of an aneurysm. This was followed by left hemiplegia and frontal lobe neglect. In
      both cases, 123I-iodoamphetamine single photon emission CT disclosed a reduction
      in regional cerebral blood flow localised along the circumference of the
      haematoma in the frontal lobe, but did not reveal any lesions in the parieto
      occipital junction. These findings suggest that, in these two cases, the frontal
      lobe neglect was caused by lesions confined to the frontal lobe.

PMID- 8301312
TI  - Elastin cross-linking in the skin from patients with amyotrophic lateral
      sclerosis.
AB  - Two cross-links unique to elastin, desmosine and isodesmosine were measured and
      compared in skin tissue (left upper arm) from 10 patients with amyotrophic
      lateral sclerosis (ALS) and from seven age-matched controls. The contents of
      desmosine and isodesmosine were significantly decreased (p < 0.01 and p < 0.01,
      respectively) in patients with ALS compared with those of controls, and were
      negatively and significantly associated with duration of illness in ALS patients
      (r = -0.77, p < 0.01 and r = -0.65, p < 0.05, respectively). The decline in skin
      desmosine and isodesmosine is more rapid in ALS than in normal ageing. Thus cross
      linking of skin elastin is affected in ALS.

PMID- 8301313
TI  - Heart rate differences between right and left unilateral electroconvulsive
      therapy.
AB  - Left and right unilateral electrode placements were alternately applied in
      electroconvulsive therapy given to 21 men with melancholia. Accompanying heart
      rate elevations were greater following right unilateral treatment than left
      unilateral, apparently because of longer persistence of peak rates. This is
      consistent with right cerebral hemisphere superiority in the control of heart
      rate activity in neurologically intact humans.

PMID- 8301314
TI  - Rabies encephalitis in humans: pathology, pathogenesis and pathophysiology.

PMID- 8301315
TI  - The p53 gene and protein in human brain tumors.
AB  - p53 mutation is most likely an integral early step in the formation of a subset
      of human diffuse, fibrillary astrocytomas, but is not a frequent event in other
      studied brain tumors. In astrocytomas, p53 mutations are clustered in the
      conserved regions of the gene and are predominantly single base pair transitions,
      frequently at CpG dinucleotides. These mutations result in mutant or truncated
      p53 proteins that lack the transcriptional activating ability to induce G1
      arrest, DNA repair, apoptosis or differentiation. On the other hand, some
      astrocytomas without p53 mutations may accumulate wild-type protein, perhaps as a
      physiological response to DNA damage or deregulated proliferation in the tumor
      cells. Finally, while data on the p53 gene and protein studies in human brain
      tumors are accumulating rapidly, the clinical significance of such data remains
      unclear.

PMID- 8301316
TI  - Arteriolar tortuosity of the white matter in aging and hypertension. A
      microradiographic study.
AB  - Previous studies have shown tortuous arteries and arterioles in the brains of
      older people, but the effects of age and other factors have not been studied. To
      examine the effects of hypertension, age, race and sex on white matter (WM)
      arteriolar tortuosity (AT), we performed high-resolution microradiography and
      morphometry of human brains taken at autopsy from 44 subjects of various ages
      (range 30-96 years; 31 hypertensives/13 normotensives). About 70% of tortuosities
      in the WM were found at the gray-white interfaces of the insular region and
      adjacent subcortical-WM of the inferior frontal and superior temporal gyri. Six
      morphologic types of tortuous profiles were identified. The number of tortuous
      profiles increased with age, but not significantly. Hypertension, sex and race
      had no effect on tortuosity. Our findings also suggest that 1) WM AT is found
      mostly at the interfaces between gray matter and WM and, therefore, 2) the
      physical properties of the WM somehow predispose to the development of AT; 3) AT
      is not associated with tortuosity in the veins; and 4) the location of complex
      arteriolar coils supports a recent claim that they can be mistaken for the
      Charcot-Bouchard microaneurysms if injection of contrast media and low
      magnification radiography of the brain slices are employed for that purpose.

PMID- 8301317
TI  - Fc receptors for IgG on cultured human microglia mediate cytotoxicity and
      phagocytosis of antibody-coated targets.
AB  - We have utilized surgically resected human central nervous system (CNS) tissue to
      determine the expression and functions of Fc receptors (Fc gamma R) on individual
      cell types found within the CNS. We observed all three classes of Fc gamma R on
      microglial cells in situ and in vitro, but not on astrocytes or oligodendrocytes.
      Incubation of cultured microglia with immune complexes (antibody-coated red blood
      cells) induced phagocytosis, antibody-dependent cell-mediated cytotoxicity
      (ADCC), and oxidative bursts. We also found that microglia have the capability to
      produce T cell stimulatory soluble mediators after Fc gamma R crosslinking. These
      functional responses were enhanced by pretreatment of the microglia with
      interferon-gamma (IFN-gamma). Our results implicate microglial effector responses
      triggered by interaction of Fc gamma R with opsonized antigens as potential
      mediators of tissue injury within the CNS. Such injury may be particularly
      applicable to multiple sclerosis, an inflammatory demyelinating disease
      characterized by intrathecal production of immunoglobulins and cytokines.

PMID- 8301318
TI  - Neurochemical and histopathologic alterations characteristic of Pick's disease in
      a non-demented individual.
AB  - In the course of investigating a large number of non-demented subjects, a 68 year
      old female dying of coronary artery disease was found to have Pick bodies in her
      grossly normal brain. Although only mild subcortical gliosis and no neuron loss
      were observed. Pick bodies were found throughout the brain and occasional balloon
      cells were noted. Pick bodies and numerous neurons were also ALZ-50 and Tau-1
      immunoreactive. Retrospective studies indicated a lack of overt intellectual
      decline or depression in this individual. Frontal, temporal and occipital poles,
      amygdala, hypothalamus and nucleus basalis of Meynert (nbM) were analyzed for
      ChAT, AChE and MAO-A and -B enzymatic activities and for the binding of 5HT and
      imipramine. Cholinergic decreases were found only in subcortical structures.
      Serotonin binding decreases were widespread, excluding the nbM. Altered MAO-B
      activity was regionally variable, and no differences in MAO-A activity or
      imipramine binding were observed. Few differences in neurochemical alterations
      were observed in the current non-demented subject with abundant Pick bodies
      compared to previous studies of demented Pick's patients. This case strongly
      suggests that chemical dysfunction and neuropathological features of Pick's
      disease occur in advance of overt clinical manifestations of the disorder.

PMID- 8301319
TI  - Immunohistochemical changes and PCR detection of HIV provirus DNA in brains of
      asymptomatic HIV-positive patients.
AB  - The stage of HIV infection at which the virus enters the nervous system remains
      poorly understood. Examination of brains of HIV-positive non-AIDS patients often
      shows lymphocytic meningitis, myelin pallor and gliosis, but no
      immunohistochemical (IHC) evidence of the virus. In this study we have examined a
      number of brains from HIV-positive patients with (23) and without (8) AIDS as
      well as brains from 5 HIV-negative controls by morphological, morphometric, IHC
      and polymerase chain reaction (PCR) methods in an attempt to establish at what
      stage of the infection HIV can be detected in the brain and to correlate its
      presence with the pathological changes in the cortex. HIV-1 proviral DNA was
      found by PCR in the cortex of the majority of AIDS and in 2 out of 8 non-AIDS
      cases. Astroglial reaction was observed in the cortex of the majority of AIDS
      brains but not in most of the non-AIDS brains which showed, in addition, a
      dramatic reduction of glial fibrillary acidic protein staining around blood
      vessels; moreover, in this group the density of microglial cells was higher than
      in the AIDS group. These results show that: 1) HIV proviral DNA can be found in
      the brains of HIV-positive non-AIDS patients; 2) in the same group there is an
      increase in density of microglial cells which 3) appears to be transient, since
      AIDS brains without neuropathology show a lower density of these cells. They also
      suggest that the status of 'immune reaction' existing in AIDS may predate this
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301320
TI  - Macrophage properties during peripheral nervous tissue rejection in vitro.
AB  - The present study introduces an in vitro model of xenogeneic peripheral nerve
      rejection to analyze the role of macrophages in this complex immunological
      situation. Nerve-sensitized mouse peritoneal exudate cells were co-cultured with
      rat peripheral nerve segments. The cultured rat nerve segments were fulminantly
      rejected in vitro by the co-cultured mouse peritoneal cell population. The
      massive tissue destruction included Schwann cell damage and was quite distinct
      from basic myelin phagocytosis observed during Wallerian degeneration in earlier
      experiments. The nerve-sensitized peritoneal exudate consisted of macrophages and
      T-cells. Antibody depletion experiments were performed to analyze T-lymphocyte
      effects in this model. Fulminant tissue rejection depended on the presence of T
      lymphocytes in the culture medium. Their presence at the immediate site of tissue
      rejection, however, was not required. Further experiments were aimed at defining
      the role of T-cell-derived mediators during in vitro rejection. Depletion
      experiments using a panel of antibodies to cytokines revealed a critical
      involvement of IL-2, IL-3, IL-4, IL-6 and interferon-gamma in the induction of
      tissue rejection in vitro. Fulminant tissue rejection in vitro depended on the
      interaction of these cytokines with macrophages. The participation of macrophage
      surface receptors was studied in another series of experiments. The macrophage
      complement receptor type 3 was shown to be critically involved in the phagocytic
      attack during rejection. Antibodies to MHC class II antigens also abolished
      fulminant in vitro rejection, indicating that continuous antigen presentation is
      required in this process.

PMID- 8301321
TI  - Cerebellar dysplasias in humans: development and possible relationship to glial
      and primitive neuroectodermal tumors of the cerebellar vermis.
AB  - Cerebellar dysplasias are commonly found in the white matter and nodulus of the
      vermis in newborns and are particularly prominent in infants with trisomy 13-15
      and trisomy 18 syndromes. Little is known of the developmental biology of these
      structures. We have studied the development of cerebellar dysplasias in human
      fetuses ranging from 15 to 32 weeks gestational age and from 11 days to 15 months
      postnatal. The expression of developmentally regulated neuronal and glial
      polypeptides was investigated by immunohistochemistry using a panel of
      extensively characterized monoclonal antibodies. Dysplasias were first observed
      at 15 weeks gestation as irregularly distributed, parenchymal or perivascular
      clusters of primitive cells in the inferior vermis. These cell clusters resembled
      primitive neuroepithelial cells or cells of the cerebellar external granule cell
      layer and they persisted into postnatal life. They retained the capacity to
      undergo cell division and were weakly reactive for the low affinity nerve growth
      factor receptor but were negative for all other neuronal or glial proteins at all
      gestational ages. At about 20 weeks gestation, cerebellar dysplasias become more
      complex with the appearance of ganglion cells which matured histologically and
      phenotypically in parallel with normal dentate neurons and Purkinje cells. These
      dysplasias often contained a prominent glial component which was identified by
      immunostaining for glial fibrillary acidic protein. Our findings suggest that
      midline cerebellar dysplasias are normal variants of development. Whether the
      mitotically active cells comprising these dysplasias are targets for neoplastic
      transformation into cerebellar primitive neuroectodermal tumors or other types of
      childhood tumors such as pilocytic astrocytomas or atypical teratoid/rhabdoid
      tumors remains speculative.

PMID- 8301322
TI  - Cytokine expression in the spinal cord lesions in HTLV-I-associated myelopathy.
AB  - Immunocytochemical staining of spinal cords from five autopsied patients with
      HTLV-I-associated myelopathy/tropical spastic paraparesis was performed using a
      panel of monoclonal or polyclonal antibodies reactive with interleukin-1 beta (IL
      1 beta), interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, interferon
      (IFN)-alpha, IFN-beta, IFN-gamma and transforming growth factor (TGF)-beta. In
      the spinal cords of patients with a shorter duration of illness, IL-1 beta, TNF
      alpha, and IFN-gamma were expressed on perivascular infiltrating macrophages,
      astrocytes and microglia in active-chronic inflammatory lesions. In striking
      contrast, we rarely noted cytokine expression except for IFN-gamma in inactive
      chronic lesions of patients with longer durations. In situ expression of these
      cytokines on microglia and astrocytes, in addition to infiltrating mononuclear
      cells, suggests that glial cells participate in the inflammatory process,
      especially in active lesions. In addition, the cytokine expression was gradually
      downregulated along with duration of illness.

PMID- 8301323
TI  - Co-expression of mRNA for neurotrophic factors in human neurons and glial cells
      in culture.
AB  - Enriched populations of neurons and astrocytes of 93-99% purity were obtained
      from mixed cultures of four human fetal brains. Total cellular RNA was extracted
      from cell pellets and reverse transcribed into cDNA. Five microliters of cDNA
      were subjected to PCR amplification using primers specific for sequences of NGF,
      BDNF, NT-3 and CNTF. PCR products were separated through 5% acrylamide gel and
      identified by DNA sequencing. Results showed that neurons expressed detectable
      levels of mRNA for NGF in all four cultures; BDNF and NT-3 mRNA was seen only in
      two cultures; CNTF mRNA was not detected in all four cultures. Astrocytes
      expressed mRNA for NGF, BDNF, and NT-3 but not for CNTF in all cultures examined.
      Astrocytic expression of mRNA for NGF, BDNF and NT-3 was found during the active
      cell proliferation as well as at a phase of mitotic quiescence. This study
      provides evidence that dissociated cell cultures of human neurons produce NGF,
      BDNF and NT-3 in early stages of their development and that astrocytes are
      constitutively committed to synthesize neurotrophic factors, NGF, BDNF and NT-3.
      The active synthesis of selected neurotrophic factors by neurons and astrocytes
      is relevant in supporting migration, survival and differentiation of developing
      neurons in vivo.

PMID- 8301324
TI  - HIV antigen and DNA in AIDS spinal cords correlate with macrophage infiltration
      but not with vacuolar myelopathy.
AB  - Since the relationship between vacuolar myelopathy (VM) and HIV infection of the
      spinal cord is unclear, we studied 74 cases of VM in AIDS patients for associated
      spinal cord and brain diseases, the presence of HIV antigens (n = 54) and
      amplified DNA (n = 7) and serum levels of vitamin B12 and folic acid (n = 6).
      Necrosis of the medial F. gracilis was present in 14%, HIV myelitis in 9%,
      cytomegalovirus myelitis in 3% and microglial nodules in 16%. HIV-immunoreactive
      macrophages were encountered in 6% of VM cords; they were in regions of gracile
      tract necrosis in two and in monocytes and multinucleated cells in spinal gray
      matter in one. Amplified HIV DNA was detected in 50% of cords and 70% of dorsal
      root ganglia (DRG) of cases with moderate or severe VM and 63% of cords and 75%
      of DRG in AIDS cases without VM. Six of the eight spinal cords with HIV DNA
      contained macrophages whereas all cords without HIV DNA (n = 6) were normal or
      contained only rare macrophages. There was no association between VM and HIV
      myelitis or opportunistic infections of the CNS, but there was a close
      association with HIV encephalitis which occurred in 80% of severe VM, 33% of
      moderate VM and 17% of mild VM. Vitamin B12 and folic acid levels were normal or
      elevated in all six AIDS with VM as well as in 12 AIDS without VM; all had
      received prophylactic vitamin therapy prior to death.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8301325
TI  - 192 IgG-saporin: I. Specific lethality for cholinergic neurons in the basal
      forebrain of the rat.
AB  - An immunotoxin (IT) composed of a monoclonal antibody to the nerve growth factor
      (NGF) receptor, 192 IgG, chemically linked to saporin, 192 IgG-saporin, was shown
      to selectively reduce forebrain choline acetyltransferase (ChAT) activity in the
      rat brain following intraventricular administration. In order to determine if the
      IT was killing NGF receptor-positive neurons in the CBF (rather than simply
      suppressing the cholinergic phenotype in these cells), a population of neurons in
      the nucleus basalis magnocellularis (NBM) was prelabeled by an intracortical
      injection of the neurotracer Fluoro-Gold (FG) 1 week before intraventricular
      injections of IT or control substances (reduced IT or phosphate-buffered saline).
      We found that there were very few double-labeled (i.e. FG-labeled and ChAT
      positive) neurons remaining in the NBM of IT-treated animals. The absolute number
      of FG-labeled neurons in the NBM of IT-treated animals was reduced by a number
      similar to the counts of double-labeled neurons in the NBM of control animals.
      Our conclusion is that the IT is preferentially lethal to cholinergic neurons in
      the NBM. Due to its ability to selectively kill cholinergic neurons in the CBF
      and concomitantly spare noncholinergic neurons with similar morphology and
      projections, 192 IgG-saporin can be used to produce a selective model of CBF
      deficit in the rat.

PMID- 8301326
TI  - A discrete group of melanin containing cells are coincident with a major
      reorganization of retinal ganglion cell axons in the optic nerve of Xenopus.
AB  - Further investigations into the abrupt reorganization of axons in the proximal
      optic nerve of the frog Xenopus are presented. This reorganization reverses the
      radial, age-related organization of the projection. At the site of axon
      divergence a discrete group of melanin-producing astrocytes occurs, which are
      coincident with the reorganization. These cells are identified as astrocytes by
      their ultrastructure, and by staining in vitro with an antibody to glial
      fibrillary acidic protein. In an attempt to see if this reorganization occurs in
      the absence of pigmented astrocytes, the periodic albino mutant of Xenopus was
      examined. In this albino a similar reorganization of the retinal axons occurs in
      the optic nerve, but there is also a population of pigment-containing astrocytes.
      Unlike the pigment of retinal pigment epithelium, which is lost during
      metamorphosis in these albinos, the pigmented astrocytes of the optic nerve
      retain their pigment throughout life. A second approach, used to provide support
      for the involvement of these pigmented astrocytes in the reorganization, was to
      study the development of the projection. In early development there is a period
      prior to gliogenesis in the optic nerve (Stage 47/48) when no pigmented cells are
      present. At these early stages of development there is no evidence for a
      reorganization of the retinal axons in the optic nerve. The possible role of
      these melanin-containing astrocytes in axon guidance is discussed.

PMID- 8301327
TI  - Myelin formation by mouse glia in myelin-deficient rats treated with
      cyclosporine.
AB  - Previous attempts to generate myelin in the myelin-deficient rat spinal cord by
      transplanting mouse glia were not successful. In order to determine whether this
      result was due to graft rejection or to interspecies mismatch of cellular or
      molecular components at the axoglial junction, we have repeated the experiment in
      cyclosporine-treated rats. Our results show that in the immunosuppressed hosts,
      foetal glial xenografts form an abundance of myelin within the dorsal columns at
      or near the injection site about two weeks after the operation. In some cases,
      myelination extends virtually across the entire width of the dorsal columns.
      Ultrastructurally, the myelin sheaths are normal in all respects, including the
      presence of the 'radial component'. The lateral edges of the myelin lamellae form
      typical paranodal axoglial junctions, some displaying periodic 'transverse
      bands'. We infer that previous mouse to rat xenograft failures reflect host
      immune response rather than mismatch of heterologous junctional components. We
      also compared foetal, early post-natal and adult xenografts. Foetal donor cells,
      containing an abundance of precursors but virtually no mature oligodendrocytes,
      are more effective than neonatal donor cells in forming myelin, and after adult
      grafts, we found no myelin formation. Thus, in xenografts, as in allografts,
      foetal precursor cells are far more suitable than glia from mature donors in
      generating significant amounts of myelin.

PMID- 8301328
TI  - Presynaptic fibres of spiral neurons and reciprocal synapses in the organ of
      Corti in culture.
AB  - Isolated segments of the newborn mouse organ of Corti were explanted together
      with the spiral ganglion components. Within the innervation provided by the
      spiral neurons, we observed presynaptic vesiculated nerve endings that form
      reciprocal ribbon-afferent/efferent synapses with inner hair cells. These
      intracochlear presynaptic fibres are characteristically located between adjoining
      inner hair cells, on the modiolar side, low and close to the supporting cells.
      The presynaptic fibres display different modes of synaptic connectivity, forming
      repetitive reciprocal synapses on single inner hair cells or on adjoining hair
      cells, or connecting adjoining inner hair cells through simultaneous efferent
      synapses. Many presynaptic fibres exhibit a distinctive ultrastructure: defined
      clusters of synaptic vesicles, dense core vesicles, coated vesicles, and
      mitochondria. These organelles occur focally at the synaptic sites; beyond the
      efferent synaptic specializations, the endings appear quite nondescript and
      afferent-like. We believe that the reciprocal synapses, although observed in
      cultures of the organ of Corti, represent real intracochlear synaptic
      arrangements providing a feedback mechanism between the primary sensory receptors
      and a special class of spiral ganglion cells that have yet to be recognized in
      the organ in situ.

PMID- 8301329
TI  - Immunoelectron microscopic localization of the HPC-1 antigen in rat cerebellum.
AB  - HPC-1 antigen is a neuron-specific 34 kDa protein, identical to p35A (syntaxin),
      and is thought to play important roles in docking or fusion of synaptic vesicles
      to presynaptic active zones. In the present study we analyze the distribution of
      HPC-1 antigen in rat cerebellum by a cryoimmunogold technique using an antibody
      against the fusion protein of beta-galactosidase and the HPC-1 antigen. HPC-1
      antigen was detected at high density on the plasma membranes and synaptic
      vesicles of presynaptic boutons which formed synapses with dendrites of Purkinje
      cells, and on the plasma membranes of parallel fibres in the cerebellar molecular
      layer. In the granule cell layer, gold particles were also detected on the
      endoplasmic reticulum, nuclear membranes and the plasma membranes of granule
      cells. Presynaptic membranes and synaptic vesicles in glomeruli were also
      labelled by gold particles. To determine the topology of HPC-1 antigen on the
      membranes, the synaptosome fraction prepared from rat cerebellum was embedded in
      agarose, and processed for the pre-embedding protein A-gold technique. Intact
      synaptosomes were not labelled by gold particles. However, when fixed in
      hypotonic fixative to rupture plasma membranes, or when ruptured after fixation
      in normotonic fixative, the cytoplasmic surfaces of presynaptic membranes and
      synaptic vesicles were labelled by gold particles. These results suggest that
      most of the epitopes of HPC-1 antigen are located on the cytoplasmic surface of
      plasma membranes and synaptic vesicle membranes.

PMID- 8301330
TI  - Pulse oximetry, capnography, and blood gas measurements: reducing cost and
      improving the quality of care with technology.
AB  - Pulse oximetry appears to improve quality of care by the early detection of
      hypoxia noninvasively. We tested the hypothesis that the widespread use of pulse
      oximetry over a 5-year period in the operating rooms at our institution had
      resulted in a reduction in blood gas measurements and in departmental operating
      costs. The total number of blood gas determinations per hour of anesthetic time
      at our institution decreased by 44%, from 7.64 to 4.26 measurements per 100
      operating room hours. The number of capnography units in the operating rooms
      increased from 8 to 14, the number of pulse oximeters increased from 0 to 22, and
      oximeter use increased from 0 to 100% for all anesthetics. The total cost to
      provide oximetry, capnography, and blood gas measurements in 1989-1990 was less
      than the cost to provide blood gas measurements alone in 1985-1986. The
      introduction of these technologies was accomplished without an increase in cost:
      $76,880 in 1985-1986 versus $71,025 in 1989-1990.

PMID- 8301331
TI  - Stability and long-term durability of Raman spectroscopy.
AB  - OBJECTIVE: The purpose of this study was to assess in the clinical setting the
      reliability and long-term stability of Raman spectroscopy as implemented in the
      RASCAL multiple gas analyzer, and to describe/analyze failure modes that manifest
      in regular use. METHODS: Twenty-one RASCAL analyzers were tested for accuracy and
      precision. Without any prior external calibration or alignment, all gas analyzers
      were systematically tested over a consecutive 36-hour period with standard gas
      mixtures. Data were analyzed by evaluating the difference between the predicted
      value and observed value (bias residual) as reported by each RASCAL: All service
      data (29 months) also were analyzed for information on durability and failure
      modes. RESULTS: The RASCAL exhibited a significant tendency to overread high
      concentrations of agent (isoflurane/enflurane); 4 of 16 instruments misread an
      agent by more than +/- 0.30%. Four of 16 instruments could not properly identify
      volatile agents in low concentrations (0.31 vol%). Inventory records show that
      water contamination led to the replacement of gas sample sets an average of 1.5
      +/- 1.2 times per case over the 29-month period. Although many instruments had
      not been externally calibrated for over 63 days, linearity proved acceptable for
      CO2, O2, N2O, and N2. A rationale for instrument behavior and major failure
      modes, based on the instrument design, was developed. CONCLUSIONS: The
      manufacturer's suggested calibration intervals (30 days) were found to be more
      than adequate for reliable gas analysis using Raman spectroscopy. Without the
      benefit of frequent calibrations and as time passes, volatile agent
      quantification can be expected to drift significantly upward.

PMID- 8301332
TI  - Quantitative testing of sympathetic function with laser Doppler flowmetry.
AB  - OBJECTIVE: The objective of this study was to develop an indirect technique for
      evaluating dynamic changes in sympathetic function in humans. METHODS: We used
      laser Doppler to monitor sympathetic mediated vasoconstrictive responses (VRs)
      produced by 3 different provocative stimuli: 4-second inspiratory gasp (IG), ice
      water immersion (Ice), and a spring-loaded pin prick (Pin). Skin perfusion on the
      thenar eminence was continuously monitored in 10 normal subjects (aged 25 to 36
      years) using laser Doppler. Ten trials of the 3 stimuli were presented to each
      subject at 1-minute intervals. We determined the VR, the percent decrease in
      perfusion produced by each stimulus, and the 2 standard deviation variation in
      perfusion. RESULTS: No subject found the IG maneuver uncomfortable. In contrast,
      the Pin and Ice stimuli were reported to be uncomfortable by 8 and 10 subjects,
      respectively. Five subjects found Pin and Ice stimuli overtly painful.
      Vasoconstrictive response was 54.1 +/- 2.3% (mean +/- SEM) with IG, 49.2 +/- 2.0%
      with Ice, and 24.0 +/- 1.8% with Pin. Baseline variation was approximately 15% in
      all trials. CONCLUSION: Inspiratory gasp vasoconstrictive response (IGVR) is a
      sensitive indirect technique for evaluating sympathetic efferent function. We
      observed that the magnitude of the VR elicited by the IG stimuli was similar to
      that induced by cold water. Unlike the VR induced by Pin or Ice, IGVR is not
      dependent on noxious input via somatic afferents; therefore, it can be used in
      patients with diseases that produce a peripheral neuropathy, such as diabetes
      mellitus. Present uses of this technique and speculation on future uses are
      presented.

PMID- 8301333
TI  - Analytical methods to differentiate similar electroencephalographic spectra:
      neural network and discriminant analysis.
AB  - Differences in electroencephalographic (EEG) power spectra obtained under
      similar, but not identical, conditions may be difficult to discern using standard
      techniques. Statistical analysis may not be useful because of the large number of
      comparisons necessary. Visual recognition of differences also may be difficult. A
      new technique, neural network analysis, has been used successfully in other
      problems of pattern recognition and classification. We examined a number of
      methods of classifying similar EEG data: standard statistical analysis (analysis
      of variance), visual recognition, discriminant analysis, and neural network
      analysis. Twenty-nine volunteers received either thiopental (n = 9), midazolam (n
      = 10), or propofol (n = 10) in sedative doses in 3 different studies. These drugs
      produced very similar changes in the EEG power spectra. Except for beta 2 power
      during thiopental infusion, differences between drugs could not be detected using
      analysis of variance. Visual categorization was correct in 72% of the baseline
      EEGs, 70% of thiopental EEGs, 27% of propofol EEGs, and 46% of midazolam EEGs. A
      classification neural network (Learning Vector Quantization network) containing a
      Kohonen hidden layer was able to successfully classify 57 of 58 EEG samples (of 4
      minutes' duration). Discriminant analysis had a similar rate of success. This
      level of performance was achieved by dividing the EEG power spectrum from 1 to 30
      Hz into 15 2-Hz bandwidths. When the EEG power spectrum was divided into the
      "classical" frequency bandwidths (alpha, beta 1, beta 2, theta, delta), both
      neural network and discriminant analysis performance deteriorated. By training
      the network using only certain inputs we were able to identify drug-specific
      bandwidths that seemed to be important in correct classification. We conclude
      that propofol, thiopental, and midazolam produce different effects on the EEG and
      that both neural network and discriminant analysis are useful in identifying
      these differences. We also conclude that EEG spectra should be analyzed without
      using classical EEG bands (alpha, beta, etc.). Additionally, neural networks can
      be used to identify frequency bands that are "important" in specific drug effects
      on the EEG. Once a classification algorithm is obtained using either a neural
      network or discriminant analysis, it could be used as an on-line monitor to
      recognize drug-specific EEG patterns.

PMID- 8301334
TI  - Experimental and predicted dual oximetry variability.
AB  - OBJECTIVE: We wished to determine whether the individual bias (mean difference)
      and precision (standard deviation of the difference) values of 2 variables,
      arterial oxygen saturation (SaO2) and mixed venous oxygen saturation (SvO2),
      could be used to predict the bias and precision values of the combined dual
      oximetry variable (SaO2-SvO2). METHODS: We simultaneously measured SaO2 by pulse
      oximetry and arterial blood gas co-oximetry and SvO2 by fiberoptic reflectance
      oximetry pulmonary artery catheter and venous blood gas co-oximetry in 238 data
      sets from 55 patients. Three different methods were used to predict the standard
      deviation of the difference of (SaO2-SvO2) [s delta(SaO2-SvO2)]: simple sum, root
      mean square (RMS) error, and RMS error with correction term. We derived the
      equation for the RMS error with correction term because initial results showed
      that the simple sum and RMS error methods did not predict s delta(SaO2-SvO2)
      well. The correction term accounts for the non-independence of simultaneous SaO2
      and SvO2 measurements. RESULTS: The observed overall bias of the SaO2, SvO2, and
      (SaO2-SvO2) measurement methods were 0.17, -1.76, and 1.94, respectively. The
      observed overall s delta(SaO2-SvO2) of the (SaO2-SvO2) measurement method was
      5.12. The simple sum method overestimated the actual s delta(SaO2-SvO2) by 38%,
      the RMS error method differed from the actual s delta(SaO2-SvO2) by 3%, and the
      RMS error with correction term method matched the actual s delta(SaO2-SvO2).
      CONCLUSION: The bias of a (SaO2-SvO2) measurement method is simply the bias of
      the SaO2 measurement method less the bias of the SvO2 measurement method. s
      delta(SaO2-SvO2) is best predicted by the derived equation, RMS error with
      correction term. The same principles and equations also apply to other situations
      in which 2 variables with the same dimensions are combined into 1 variable, such
      as (PaCO2-EtCO2) gradients and perfusion-pressure gradients. Although the
      difference between the s delta(SaO2-SvO2) predicted by the RMS error equation and
      the derived RMS error equation with correction term was small, the difference may
      be significant for other combined variables.

PMID- 8301335
TI  - Comparison of six methods to calculate airway resistance during mechanical
      ventilation in adults.
AB  - OBJECTIVE: A variety of methods are used to calculate indices of lung mechanics.
      We conducted this study to compare 6 methods of calculating airway resistance.
      METHODS: Data were recorded from 20 adult mechanically ventilated patients. All
      were relaxed and breathing in synchrony with the ventilator, and an end
      inspiratory pause sufficient to produce a pressure plateau (0.5-1.5 s) was used.
      Pressure and flow rate were measured at the proximal airway using a calibrated
      lung mechanics analyzer (VenTrak, Med Science, St Louis, MO). Flow rate,
      pressure, and volume were printed simultaneously. Airway resistance was
      calculated using 6 methods: Suter, Krieger, Neergard, Bergman, Comroe, and
      Jonson. RESULTS: Mean calculated resistances (+/- SD) (cm H2O/L/s) were 11.7 +/-
      4.8 (Suter method), 13.3 +/- 5.0 (Krieger method), 14.9 +/- 5.3 (Neergard
      method), 25.0 +/- 6.6 (Bergman method), 24.7 +/- 6.4 (Comroe method), and 26.9 +/
      4.8 (Jonson method). By repeated measures analysis of variance, these
      differences were significant (p < 0.001). Using Scheffe analysis, no difference
      was found between the calculations using the Bergman, Comroe, and Jonson methods;
      these were significantly greater than the other 3 methods (p < 0.05).
      CONCLUSIONS: Methods that evaluate expiratory resistance (Comroe, Bergman, and
      Jonson) produce higher values than methods that evaluate inspiratory resistance
      (Suter and Neergard) or a combination of inspiratory and expiratory resistance
      (Krieger). Because of these differences, investigators should clearly describe
      their calculations when reporting airway resistance values.

PMID- 8301336
TI  - The detection of peripheral venous pulsation using the pulse oximeter as a
      plethysmograph.
AB  - The pulse oximeter can serve as a sensitive photoelectric plethysmograph in the
      operating room. It was noted in several cases that the plethysmographic waveform
      showed a high degree of variability during diastole. Three patients are described
      with discrete diastolic peaks on the plethysmograph. Further investigation
      revealed that these diastolic peaks appear to correlate with peripheral venous
      pulsation, which seems to have a central venous origin. Evidence is presented
      that the plethysmographic detection of the venous-pulse may be useful in
      estimating the changing volume status of the patient.

PMID- 8301337
TI  - Fatal cardiac perforation caused by the dilator of a central venous
      catheterization kit.
AB  - We report a case of cardiac perforation and tamponade caused by the dilator of a
      central venous catheterization kit. Standards for dilator manufacture and
      guidelines for safe use of these instruments are suggested.

PMID- 8301338
TI  - Erroneous data from an infrared anesthetic gas analyzer.

PMID- 8301339
TI  - Intraperitoneal hemorrhage following femoral artery cannulation for
      intraoperative monitoring: an unusual complication.

PMID- 8301340
TI  - Algorithm to identify components of arterial blood pressure signals during use of
      an intra-aortic balloon pump.
AB  - Existing bedside cardiovascular monitors often inaccurately measure arterial
      blood pressure during intra-aortic balloon pump (IABP) assist. We have developed
      an algorithm that correctly identifies features of arterial pressure waveforms in
      the presence of IABP. The algorithm is adaptive, functions in real-time, and uses
      information from the electrocardiographic (ECG) and arterial blood pressure
      signals to extract features and numeric values from the arterial blood pressure
      waveform. In its current form, it requires reliable ECG beat detection and was
      not intended to operate under conditions of extremely poor balloon timing. The
      algorithm was evaluated by an expert (P.F-C.) on a limited data set, which
      consisted of 12 1-minute epochs of data recorded from 6 intensive care unit
      patients. A criterion for selection of patients was that the ECG beat detector
      could detect ECG beats correctly from the waveforms. The overall sensitivity and
      positive predictivity for beat detection were 94.04% and 100%, respectively. For
      feature identification, the overall sensitivity was greater than 89%, positive
      predictivity was 100%, and the false-positive rate was 0%. The performance
      measures may be biased by the criteria for patient selection. This approach to
      identifying waveform features during IABP improves the accuracy of measurements.
      The utility of using 2 sources of information to improve measurement accuracy has
      been demonstrated and should be applicable to other physiologic signal-processing
      applications.

PMID- 8301341
TI  - Inaccurate capnograph waveform.

PMID- 8301343
TI  - Sequential change of capillary permeability in the rat brain after surgical
      removal of an experimental brain tumor.
AB  - Experimental brain tumors were excised from rats for sequential observation of
      changes in local capillary permeability during the postsurgical period.
      Experimental brain tumor-bearing rats were prepared by stereotaxic
      transplantation of cultured tumor cells and the resultant tumor was delineated by
      administration of a dye. Following excision of the stained tumor by craniotomy,
      sequential changes in local capillary permeability were quantitatively followed
      up by autoradiography, using 14C-amino-isobutyric acid as a tracer. Capillary
      permeability was enhanced following surgery, reaching a maximum both in the
      extent and degree on the third day. After undergoing a gradual reduction, it
      showed a marked increase for the second time in a very small area on the 10th
      postoperative day. A recurrence of the tumor was responsible for this late but
      marked increase. For a control group, the caudate nucleus was excised from normal
      rats, followed by observation of the sequential changes in the local capillary
      permeability. Due to surgical procedure, capillary permeability reached a maximum
      both in the extent and degree on the 5th postoperative day (slightly later than
      in the tumor group). This change in capillary permeability was less pronounced
      than in the tumor group. The difference in the conditions of surgery--tumor
      excision and partial excision of a normal brain tissue--appeared to explain this
      difference. The results of this study indicated that it is more desirable to give
      water-soluble antineoplastic agents early during the postoperative period for
      chemotherapy of a malignant brain tumor after surgery.

PMID- 8301342
TI  - The effect of prolactin and bombesin on the growth of meningioma-derived cells in
      monolayer culture.
AB  - Meningioma growth is thought to be stimulated by the sex hormones progesterone
      and possibly estrogen. We report here stimulation of growth of meningioma-derived
      cells in culture by prolactin. Fourteen human tumors taken from surgery were
      initially grown in Ham's medium F10 with 15% fetal calf serum. The tumors were
      then trypsinized and resuspended in medium in a multi-well plate with either
      prolactin or bombesin; the cells were incubated for 1 week, washed, and
      resuspended for cell counting. The growth-stimulating effect of prolactin at 10
      and 200 micrograms/ml was compared with bombesin at 5 mM/ml or 15 mM/ml. A growth
      index compared cell count in the experimental well to the control well; growth at
      the rate of the control well was given an index of 1.0. The tumors included 7
      meningiomas and 7 other neoplasms (3 astrocytomas, an ependymoma, a
      pineoblastoma, a hemangiopericytoma, and a metastatic adenocarcinoma). For
      meningiomas incubated in 10 micrograms/ml prolactin, the growth index was 3.08;
      for those incubated in 200 micrograms/ml prolactin, it was 2.28. Bombesin indices
      were 1.7 and 1.2 at 5 mM/ml and 15 mM/ml, respectively. By 2-tailed t-testing
      both prolactin concentrations stimulated the growth of meningiomas significantly
      (P < or = 0.02), while bombesin did not. Neither peptide enhanced the growth of
      the other tumors tested.

PMID- 8301344
TI  - Evidence for a calmodulin inhibitory substance(s) isolated from human
      meningiomas.
AB  - Calmodulin (CaM), a calcium-binding protein, is present in human tumor tissues
      and in meningioma. Following a purification procedure using DEAE-cellulose and
      the polymeric resin 3520, the CaM content of tumor extracts was assayed using CaM
      deficient phosphodiesterase (PDE). In the presence of low amounts of the
      extracts, a concentration dependent stimulation of PDE was observed. However,
      further addition of higher concentrations of the extract produced a marked
      inhibition of the CaM stimulation of PDE in 13 of 15 specimens. A wide range
      (2.44-51.31 units/1 mg tumor [wet weight]) of inhibitor concentration was noted.
      However, no detectable inhibitory activity of this magnitude was observed in
      normal human meningeal extracts. The final extracts showed no calcineurin
      phosphatase activity in the presence of Ni++, a known activator of this
      phosphatase. SDS-polyacrylamide gel (10%) electrophoresis of the extracts
      revealed the typical calmodulin band at 17 kDa plus two additional bands with
      apparent molecular masses of 21 and 36 kDa respectively. These bands were not
      seen using normal meningeal extracts.

PMID- 8301345
TI  - Capillary permeability in experimental rat glioma and effects of intracarotid
      CDDP administration on tumor drug delivery.
AB  - We have examined the capillary permeability within and adjacent to experimental
      rat gliomas, and the effect of intracarotid administration of cisplatin in this
      model. Permeability to 14C-sucrose was 25-fold and six-fold higher within the
      brain tumor and in the tumor periphery and adjacent tissue respectively than in
      the normal cortex. Intracarotid administration of cisplatin resulted in ten-fold
      increase in experimental gliomas and also a significant increase in the tumor
      periphery and adjacent tissue, when compared to the intravenous route.
      Intracarotid administration of cisplatin to rat did not cause acute vascular
      damage in either the brain or brain tumor at the dosage used.

PMID- 8301346
TI  - Solitary brain metastases from carcinoma of the bladder.
AB  - We report 6 cases of solitary brain metastasis from bladder carcinoma. Although
      systemic metastases from this cancer are frequent, central nervous system
      metastases are rare. Analysis of our material and of published cases shows that
      the tumor is resistant to therapy and the prognosis is consequently very poor.

PMID- 8301347
TI  - Brain metastasis from clear cell sarcoma of the kidney--a case report and review
      of the literature.
AB  - We describe a 5 year old boy with a 5.5 cm right frontal lobe brain metastasis
      from primary clear cell sarcoma of the kidney without evidence of tumor
      associated edema or contrast enhancement on either computed tomography or
      magnetic resonance imaging. The metastasis regressed but did not disappear with
      chemotherapy and dexamethasone, and the residual tumor was removed surgically. On
      histological examination the majority of the tumor was composed of mature
      connective tissue with a rim of typical renal clear cell sarcoma cells at the
      brain-tumor interface. The avascular and desmoplastic nature of the metastasis
      may explain the unusual radiographic features. Brain metastases from this tumor
      have only infrequently been reported; therefore a brief review of this rare tumor
      is provided.

PMID- 8301348
TI  - Design of a cap for radioshielding during treatment with interstitial 125I brain
      implants.
AB  - A practical radiation shielding cap has been constructed for use during 125I
      brain implants. The cap is comfortable enough to be worn continuously during a 6
      day implant and provides complete shielding from the implanted radioactive
      sources.

PMID- 8301349
TI  - Estrogen differentially regulates estrogen and nerve growth factor receptor mRNAs
      in adult sensory neurons.
AB  - We have previously shown that neurons in the basal forebrain colocalize the
      neurotrophin receptor p75NGFR and estrogen receptors. The present study was
      designed to examine (1) if neural neurotrophin targets respond to estrogen as a
      general phenotypic feature and (2) if NGF receptor mRNAs are regulated by
      estrogen, using a prototypical target of NGF, the dorsal root ganglion (DRG)
      (sensory) neuron. We demonstrate, for the first time, the presence of estrogen
      receptor mRNA and protein (binding sites) in adult female rat DRG. Moreover,
      estrogen receptor mRNA expression, while present in DRG neurons from both the
      ovariectomized (OVX; estrogen deficient) and intact female rat, was
      downregulated, as in the adult CNS, during proestrus (high estrogen levels) and
      in OVX animals replaced with proestrus levels of estrogen, as compared to OVX
      controls. In contrast, although the mRNAs for the NGF receptors p75NGFR and trkA
      were also expressed in DRG neurons from OVX and intact animals, expression of
      both NGF receptor mRNAs was upregulated in sensory neurons during proestrus, as
      compared to the OVX condition. Estrogen replacement, on the other hand, resulted
      in a transient downregulation of p75NGFR mRNA and a time-dependent upregulation
      of trkA mRNA. Estrogen regulation of NGF receptor mRNA in adult peripheral neural
      targets of the neurotrophins supports the hypothesis that estrogen may regulate
      neuronal sensitivity to neurotrophins such as NGF and may be an important
      mediator of neurotrophin actions in normal neural function and following neural
      trauma.

PMID- 8301350
TI  - GAP-43 transgenic mice: dispersed genomic sequences confer a GAP-43-like
      expression pattern during development and regeneration.
AB  - Using transgenic mice, we have examined the expression pattern conferred by
      regions of genomic GAP-43 coupled to beta-galactosidase. We demonstrate that gene
      constructions that include the GAP-43 5'-flanking region along with sufficient
      sequences of the first intron drive beta-galactosidase (lacZ) expression to mimic
      in many regards the complex spatial and temporal pattern of endogenous GAP-43
      expression. Transgene expression reaches peak levels during development, and
      persists at high levels in particular adult brain regions, such as the
      hippocampus and olfactory bulb. The inclusion of a stretch of the first intron in
      the construction is necessary to prevent expression outside of the nervous
      system, indicating that some of the cell specificity of GAP-43 expression is due
      to suppression of expression in inappropriate tissues. Injury caused by sciatic
      nerve crush causes reexpression of the transgene in adult sensory and motor
      neurons. This genomic region of GAP-43, therefore, includes elements responsive
      to neuronal growth signals that regulate both development and regeneration.

PMID- 8301351
TI  - Kv3.3b: a novel Shaw type potassium channel expressed in terminally
      differentiated cerebellar Purkinje cells and deep cerebellar nuclei.
AB  - A two-step hybridization/subtraction procedure was employed to isolate markers
      for the later stages of Purkinje cell differentiation. From this screen, a novel
      Shaw potassium channel cDNA (Kv3.3b) was identified that is developmentally
      regulated. Expression of this channel is highly enriched in the brain,
      particularly in the cerebellum, where its expression is confined to Purkinje
      cells and deep cerebellar nuclei. Sequence analysis revealed that it is an
      alternatively spliced form of the mouse Kv3.3 gene, and that the previously
      reported Kv3.3 mRNA (Ghanshani et al., 1992) is not expressed in cerebellum.
      Expression of the Kv3.3b mRNA begins in cerebellar Purkinje cells between
      postnatal day 8 (P8) and P10 and continues through adulthood, coinciding with
      elaboration of the mature Purkinje cell dendritic arbor. The timing of expression
      of Kv3.3b mRNA is maintained in mixed, dissociated primary cerebellar cell
      culture. These results suggest that the Kv3.3b K+ channel function is restricted
      to terminally differentiated Purkinje cells, and that analysis of the mechanisms
      governing its expression in vivo and in vitro can reveal molecular mechanisms
      governing Purkinje cell differentiation.

PMID- 8301352
TI  - The role of presynaptic calcium in short-term enhancement at the hippocampal
      mossy fiber synapse.
AB  - The mossy fiber synapse between dentate granule cells and CA3 pyramidal cells in
      the guinea pig hippocampus shows a robust short-term synaptic enhancement. We
      have simultaneously measured presynaptic residual free calcium ([Ca2+]i) and
      postsynaptic field potentials at this synapse to examine the role of [Ca2+]i in
      this enhancement. Single action potentials produced an increase in [Ca2+]i of 10
      50 nM that decayed to resting levels with a time constant of about 1 sec. Trains
      of action potentials produced larger [Ca2+]i increases that returned more slowly
      to resting levels. Following the onset of moderate frequency stimulus trains (0.1
      5 Hz), synaptic transmission and [Ca2+]i both increased and eventually plateaued.
      During the steady-state phase a linear relationship between [Ca2+]i and synaptic
      enhancement was observed. During the initial buildup, however, [Ca2+]i rose more
      rapidly than synaptic enhancement. Similarly, during the decay phase immediately
      following termination of a stimulus train, [Ca2+]i returned to prestimulus levels
      faster than synaptic enhancement. High concentrations of the calcium buffer EGTA
      in the presynaptic terminal slowed the buildup and decay of both [Ca2+]i and
      synaptic enhancement produced by stimulus trains. Under these conditions, the
      time course of [Ca2+]i and synaptic enhancement were well matched. This suggests
      that, despite the differences in kinetic rates observed for normal buffering
      conditions, increases in [Ca2+]i play a causal role in short-term enhancement. An
      increase in [Ca2+]i of 10-30 nM produced a twofold enhancement. We propose a
      simple kinetic model to explain these results. The model assumes that synaptic
      enhancement is controlled by a Ca-dependent first-order reaction. According to
      this scheme, a change in [Ca2+]i alters neurotransmitter release, but the slow
      kinetics of the underlying reaction introduces a temporal filter, producing a
      delay in the change in synaptic enhancement.

PMID- 8301353
TI  - Toxicity of an antitumor ribonuclease to Purkinje neurons.
AB  - Purkinje cell toxicity is one of the characteristic features of the Gordon
      phenomenon, a syndrome manifested by ataxia, muscular rigidity, paralysis, and
      tremor that may lead to death (Gordon, 1933). Two members of the RNase
      superfamily found in humans, EDN (eosinophil-derived neurotoxin) and ECP
      (eosinophil cationic protein), cause the Gordon phenomenon when injected
      intraventricularly into guinea pigs or rabbits. We have found that another member
      of the RNase superfamily, an antitumor protein called onconase, isolated from
      Rana pipiens oocytes and early embryos, will also cause the Gordon phenomenon
      when injected into the cerebrospinal fluid of guinea pigs at a dose similar to
      that of EDN (LD50, 3-4 micrograms). Neurologic abnormalities of onconase-treated
      animals were indistinguishable from those of EDN-treated animals, and histology
      showed dramatic Purkinje cell loss in the brains of onconase-treated animals. The
      neurotoxic activity of onconase correlates with ribonuclease activity. Onconase
      modified by iodoacetic acid to eliminate 70% and 98% of the ribonuclease activity
      of the native enzyme displays a similar decrease in ability to cause the Gordon
      phenomenon. In contrast, the homologous bovine pancreatic RNase A injected
      intraventricularly at a dose 5000 times greater than the LD50 dose of EDN or
      onconase is not toxic and does not cause the Gordon phenomenon. A comparison of
      the RNase activities of EDN, onconase, and bovine pancreatic RNase A using three
      pancreatic RNA substrates demonstrates that onconase is orders of magnitude less
      active enzymatically than EDN and RNase A. Thus, another member of the RNase
      superfamily in addition to EDN and ECP can cause the Gordon phenomenon.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301354
TI  - Visual search among items of different salience: removal of visual attention
      mimics a lesion in extrastriate area V4.
AB  - In more than one respect, visual search for the most salient or the least salient
      item in a display are different kinds of visual tasks. The present work
      investigated whether this difference is primarily one of perceptual difficulty,
      or whether it is more fundamental and relates to visual attention. Display items
      of different salience were produced by varying either size, contrast, color
      saturation, or pattern. Perceptual masking was employed and, on average, mask
      onset was delayed longer in search for the least salient item than in search for
      the most salient item. As a result, the two types of visual search presented
      comparable perceptual difficulty, as judged by psychophysical measures of
      performance, effective stimulus contrast, and stability of decision criterion. To
      investigate the role of attention in the two types of search, observers attempted
      to carry out a letter discrimination and a search task concurrently. To
      discriminate the letters, observers had to direct visual attention at the center
      of the display and, thus, leave unattended the periphery, which contained target
      and distractors of the search task. In this situation, visual search for the
      least salient item was severely impaired while visual search for the most salient
      item was only moderately affected, demonstrating a fundamental difference with
      respect to visual attention. A qualitatively identical pattern of results was
      encountered by Schiller and Lee (1991), who used similar visual search tasks to
      assess the effect of a lesion in extrastriate area V4 of the macaque.

PMID- 8301355
TI  - Alpha calcium/calmodulin-dependent protein kinase II selectively expressed in a
      subpopulation of excitatory neurons in monkey sensory-motor cortex: comparison
      with GAD-67 expression.
AB  - In situ hybridization histochemistry and immunocytochemistry, including double
      immunofluorescence, were used to study the populations of neurons expressing the
      alpha subunit of type II calcium/calmodulin-dependent protein kinase (CAM II
      kinase-alpha) or glutamic acid decarboxylase (GAD) in the somatic sensory and
      motor areas of the macaque monkey cerebral cortex. Sections were subjected to in
      situ hybridization using radioactive, complementary RNA probes specific for
      monkey CAM II kinase-alpha or 67 kDa GAD mRNAs. Others were stained
      immunocytochemically for CAM II kinase-alpha and/or GABA. CAM II kinase-alpha and
      GAD-67 are expressed in different populations of cells, with no colocalization.
      CAM II kinase-alpha is expressed in pyramidal cells of layers II-VI, especially
      layers II and III, as well as in certain small nonpyramidal cells of layer IV in
      areas 3a, 3b, 1, and 2 and of middle regions of area 4. Both cell types produce
      excitatory amino acid transmitters. Therefore, as in subcortical regions, CAM II
      kinase-alpha will be found on the presynaptic side of excitatory synapses but on
      the postsynaptic side only when these synapses occur on excitatory neurons in the
      sensory-motor cortex. Quantitative examination showed that CAM II kinase-alpha
      immunoreactive cells form, on average, approximately 50% of the total neuronal
      population in each area, while GABA immunoreactive or GAD cRNA hybridized cells
      form approximately 25-30%. Thus, CAM II kinase-alpha expressing cells cannot
      account for the total population of non-GABAergic cortical cells, and a certain
      proportion of the pyramidal cells probably do not express it. In other cortical
      areas, gene expression for the two molecules is regulated by afferent activity.
      Therefore, the present results form a necessary basis for studies aimed at
      determining the role of activity-dependent changes in the balance of excitation
      and inhibition as a mechanism underlying plasticity of representational maps in
      the primate sensory-motor cortex.

PMID- 8301356
TI  - Network analysis of cortical visual pathways mapped with PET.
AB  - Brain metabolic mapping techniques, such as positron emission tomography (PET),
      can provide information about the functional interactions within entire neural
      systems. With the large quantity of data that can accumulate from a mapping
      study, a network analysis, which makes sense of the complex interactions among
      neural elements, is necessary. A network analysis was performed on data obtained
      from a PET study that examined both the changes in regional cerebral blood flow
      (rCBF) and interregional correlations among human cortical areas during
      performance of an object vision (face matching) and spatial vision (dot-location
      matching) task. Brain areas for the network were selected based on regions
      showing significant rCBF or interregional correlations between tasks. Anterior
      temporal and frontal lobe regions were added to the network using a principal
      components analysis. Interactions among selected regions were quantified with
      structural equation modeling. In the structural equation models, connections
      between brain areas were based on known neuroanatomy and the interregional
      correlations were used to calculate path coefficients representing the magnitude
      of the influence of each directional path. The combination of the anatomical
      network and interregional correlations created a functional network for each
      task. The functional network for the right hemisphere showed that in the object
      vision task, dominant path influences were among occipitotemporal areas, while in
      the spatial vision task, occipitoparietal interactions were stronger. The network
      for the spatial vision task also had a strong feedback path from area 46 to
      occipital cortex, an effect that was absent in the object vision task. There were
      strong interactions between dorsal and ventral pathways in both networks.
      Functional networks for the left hemisphere did not differ between tasks.
      Networks for the interhemispheric interactions showed that the dominant pathway
      in the right hemisphere also had stronger effects on homologous left hemisphere
      areas and are consistent with a hypothesis that intrahemispheric interactions
      were greater in the right hemisphere in both tasks, and that these influences
      were transmitted callosally to the left hemisphere.

PMID- 8301357
TI  - Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in
      the rat nervous system using a selective anti-peptide antibody.
AB  - NMDA receptors play key roles in synaptic plasticity and neuronal development,
      and may be involved in learning, memory, and compensation following injury. A
      polyclonal antibody that recognizes four of seven splice variants of NMDAR1 was
      made using a C-terminus peptide (30 amino acid residues). NMDAR1 is the major
      NMDA receptor subunit, found in most or all NMDA receptor complexes. On
      immunoblots, this antibody labeled a single major band migrating at M(r) =
      120,000. The antibody did not cross-react with extracts from transfected cells
      expressing other glutamate receptor subunits, nor did it label non-neuronal
      tissues. Immunostained vibratome sections of rat tissue showed labeling in many
      neurons in most structures in the brain, as well as in the cervical spinal cord,
      dorsal root and vestibular ganglia, and in pineal and pituitary glands. Staining
      was moderate to dense in the olfactory bulb, neocortex, striatum, some thalamic
      and hypothalamic nuclei, the colliculi, and many reticular, sensory, and motor
      neurons of the brainstem and spinal cord. The densest stained cells included the
      pyramidal and hilar neurons of the CA3 region of the hippocampus, Purkinje cells
      of the cerebellum, supraoptic and magnocellular paraventricular neurons of the
      hypothalamus, inferior olive, red nucleus, lateral reticular nucleus, peripheral
      dorsal cochlear nucleus, and motor nuclei of the lower brainstem and spinal cord.
      Ultrastructural localization of immunostaining was examined in the hippocampus,
      cerebral cortex, and cerebellar cortex. The major staining was in postsynaptic
      densities apposed by unstained presynaptic terminals with round or mainly round
      vesicles, and in associated dendrites. The pattern of staining matched that of
      previous in situ hybridization but differed somewhat from that of binding
      studies, implying that multiple types of NMDA receptors exist. Comparison with
      previous studies of localization of other glutamate receptor types revealed that
      NMDAR1 may colocalize with these other types in many neurons throughout the
      nervous system.

PMID- 8301358
TI  - Cholinergic basal forebrain transplants restore diminished metabolic activity in
      the somatosensory cortex of rats with acetylcholine depletion.
AB  - It has been known for several years that stimulus-evoked metabolic activity is
      reduced in the somatosensory cortex of animals with basal forebrain lesions that
      deplete the neocortex of acetylcholine (ACh). During 2-deoxyglucose (2-DG)
      experiments, animals with unilateral basal forebrain lesions demonstrate a
      decreased response to somatic stimulation, while background metabolic activity in
      the surrounding cortical regions remains normal. In an attempt to ameliorate
      these deficits, we examined the ability of embryonic cholinergic basal forebrain
      transplants inserted into neocortex to innervate surrounding cortical regions and
      restore functional 2-DG activity in adult host rats previously depleted of ACh by
      basal forebrain lesions. To accomplish this goal, a series of experiments were
      conducted in which we (1) depleted the cerebral cortex of ACh by injecting an
      excitotoxin into the rat basal forebrain, (2) transplanted embryonic basal
      forebrain or embryonic neocortical (control) tissue into the ACh-depleted cortex
      and, (3) 6-12 months later, used the 2-DG metabolic mapping technique to examine
      effects of the transplants on metabolic activity evoked by whisker stimulation in
      rat somatosensory (barrel) cortex. Histochemical analysis revealed that
      acetylcholinesterase (AChE) staining within 2 mm of the basal forebrain
      transplants was similar in density to the contralateral normal hemisphere. AChE
      staining farther than 2 mm from the basal forebrain transplants and throughout
      hemispheres containing neocortical (control) transplants was greatly reduced,
      with few AChE-positive fibers present, a finding typical of cerebral cortex in
      basal forebrain-lesioned animals. Stimulus-evoked 2-DG uptake in barrels adjacent
      to the basal forebrain transplants, and therefore within AChE-rich territory, was
      similar to that in corresponding barrels identically activated in the
      contralateral hemisphere. 2-DG activity was reduced, however, in stimulated
      barrels outside the region of dense AChE-positive staining, as well as in all
      activated barrels in hemispheres containing control transplants of embryonic
      neocortex. These results indicate that transplantation of cell suspensions
      containing embryonic cholinergic basal forebrain, but not neocortex, can
      ameliorate basal forebrain lesion-induced deficits in functional activity, and
      that the restoration of activity is influenced by proximity to the transplant.

PMID- 8301360
TI  - Suppression of sodium channel function in differentiating C2 muscle cells stably
      overexpressing rat androgen receptors.
AB  - Differentiation of skeletal muscle and the formation of the neuromuscular
      junction are regulated by steroid hormones. The effects of androgens on ion
      channel proteins central to neuromuscular signalling have been investigated in
      differentiating mouse muscle C2 cells and in C2 cells that stably overexpress the
      rat androgen receptor (AR) cDNA. Neither the expression nor function of ACh
      receptors was regulated by androgenic actions in these cells. However, voltage
      dependent sodium (Na) current density was decreased by androgen treatment of C2
      cells and was abolished, even in the absence of androgens, in C2 cells that
      overexpress the AR. The decrease in functional Na current was not accompanied by
      concomitant decreases in Na channel mRNA, suggesting that AR influence
      posttranscriptional processing of Na channels in differentiating C2 cells.

PMID- 8301359
TI  - NK-1 and NK-3 type tachykinin receptor mRNA expression in the rat spinal cord
      dorsal horn is increased during adjuvant or formalin-induced nociception.
AB  - Substance P (SP) and other related tachykinins such as neurokinin B (NKB) have
      been studied widely as mediators of sensory information. The release of SP into
      the dorsal horn of the spinal cord is increased during nociception, and SP
      activates nociception-specific dorsal horn neurons. The tachykinin NKB has
      antinociceptive effects in the spinal cord and is contained in intrinsic spinal
      neurons; thus, NKB may also contribute to the processing of sensory information.
      Both neurokinin-1 (NK-1) and neurokinin-3 (NK-3) receptors have been localized in
      the superficial laminae of the dorsal horn. This study investigated changes in NK
      1 and NK-3 receptor mRNA expression during nociception. Following injection of
      either formalin or complete Freund's adjuvant (CFA) into one hindpaw, the levels
      of expression of NK-1 and NK-3 mRNAs in the spinal cord dorsal horn and
      preprotachykinin (PPT) mRNA expression in the lumbar dorsal root ganglia (DRG)
      were quantitated using solution hybridization-nuclease protection assays. Peptide
      and receptor mRNA expression levels were normalized to beta-actin mRNA levels,
      which did not change during the treatments. Formalin (2 or 6 hr) or CFA (4 d)
      injection produced approximately a twofold increase in SP-encoding PPT mRNA
      expression in the ipsilateral lumbar DRG. Increased activity in primary afferent
      neurons containing SP may stimulate the production of SP precursors, providing
      substrate for increased SP production, release, and turnover in the dorsal horn
      and periphery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301361
TI  - The role of the cytoplasmic domains of individual subunits of the acetylcholine
      receptor in 43 kDa protein-induced clustering in COS cells.
AB  - The 43 kDa protein, a cytoplasmic peripheral membrane protein, is closely
      associated with the acetylcholine receptor (AChR) at the neuromuscular junction,
      where it is thought to anchor the receptor in the postsynaptic membrane. We have
      used the 43 kDa protein-induced clustering of AChRs that occurs when both
      proteins are transiently expressed in COS cells to investigate which parts of the
      AChR might interact with the 43 kDa protein. By constructing chimeric subunits,
      we showed that the cytoplasmic domains of neither the epsilon nor delta subunits
      are required for 43 kDa protein-induced clustering. Systematic mutational
      analysis of the long cytoplasmic loops of the alpha and beta subunits showed that
      most of the loops can be altered without affecting the ability of the AChR to be
      clustered; in each case, however, one or more sequences could not be tested,
      because mutation in these regions prevented AChR assembly. Our results suggest
      either that these regions are involved in clustering or that the 43 kDa protein
      can interact with multiple, alternative sites on the cytoplasmic surface of the
      AChR. Our experiments also show that the postulated sites of tyrosine
      phosphorylation in the beta subunit and of serine phosphorylation in the alpha
      subunit can be mutated without affecting 43 kDa protein-induced AChR clustering.

PMID- 8301362
TI  - Extension of synaptic extracellular matrix during nerve terminal sprouting in
      living frog neuromuscular junctions.
AB  - Remodeling of the synaptic extracellular matrix (ECM) and its dynamic
      relationship with nerve terminal plasticity have been demonstrated in normal frog
      neuromuscular junctions (NMJs) in vivo (Chen et al., 1991). Our previous work has
      led to a hypothesis that extension of synaptic ECM precedes nerve terminal growth
      during synaptic remodeling. To test this hypothesis, the present study examined
      the changes of synaptic ECM in frog NMJs that were primarily undergoing nerve
      terminal growth and sprouting. Frog sartorius muscles were double stained with a
      fluorescent nerve terminal dye (4-Di-2-Asp) and rhodamine-tagged peanut
      agglutinin (PNA), which recognizes synaptic ECM. The double-labeled NMJs were
      visualized in vivo with video-enhanced fluorescence microscopy. Nerve sprouting
      was then induced in the muscle by grafting segments of the contralateral sciatic
      nerve. The identified NMJs were restrained and reexamined 2-3 months later.
      Extensive sprouting was observed in 46% of 167 identified NMJs. At junctional
      regions that showed extension or formation of new branches, synaptic ECM was
      commonly seen to have the same shape and distribution as the nerve terminal.
      However, extension of synaptic ECM beyond the corresponding nerve terminals,
      often by tens of microns, was observed in 29% of these newly formed junctional
      regions. This lack of correlation might be transient, as growth of nerve
      terminals following extended, PNA-stained ECM was seen. Examination with
      histological staining not only confirmed a lack of nerve terminal at the extended
      synaptic ECM region but also indicated an absence of AChE and postsynaptic
      junctional folds. The absence of these postsynaptic specializations at the
      extended, PNA-stained ECM region makes it unlikely that this region was
      previously occupied by nerve terminals that had retracted. Thus, the present
      study provides further findings consistent with the hypothesis that synaptic ECM
      precedes nerve terminal outgrowth and that the extension of synaptic ECM may play
      a role in synaptic remodeling.

PMID- 8301363
TI  - Early postnatal development of thyrotropin-releasing hormone (TRH) expression,
      TRH receptor binding, and TRH responses in neurons of rat brainstem.
AB  - We investigated the postnatal development of the thyrotropin-releasing hormone
      (TRH)-containing raphe system in the brainstem of neonatal rats. Postnatal
      changes in TRH expression in nucleus (n.) raphe obscurus (ROb) and n. raphe
      pallidus (RPa) were evaluated by in situ hybridization using an 35S-labeled
      oligonucleotide probe complementary to TRH precursor mRNA. TRH mRNA expression
      was low at birth [postnatal day 0 (P0)], but was clearly evident by P7 and
      increased from that time to reach sustained high levels from P14 to P28.
      Consistent with this postnatal increase in TRH expression, we found increases in
      the density of TRH-immunoreactive (IR) fibers, which are derived from ROb and
      RPa, in the hypoglossal nucleus (nXII). TRH-IR fibers in nXII were very sparse at
      P0, but increased markedly over the first 2 postnatal weeks. The change in TRH
      innervation of nXII was closely matched by concomitant increases in 3H-methyl-TRH
      binding in nXII; specific TRH binding increased from very low levels at birth to
      high levels of P14. Finally, we recorded intracellularly the electrophysiological
      responses to TRH of hypoglossal motoneurons (HMs; n = 42) of neonatal rats (P0
      P21) in a brainstem slice preparation. The response of neonatal HMs to TRH, in
      contrast to adult HMs, was highly variable. In some neonatal HMs, even at P0, TRH
      caused a depolarization with a decrease in input conductance (GN) that was
      characteristic of the response of all adult HMs. However, in other neonatal HMs,
      TRH was either without effect or caused a slight depolarization with no apparent
      change in GN, responses that were unlike those of adult HMs. A response was
      considered typical (i.e., "adult-like") if GN decreased to < 85% of control. The
      percentage of cells responding in a typical manner increased progressively from
      25% at P0-P2 to 100% after P11. In addition, we found that the density of TRH
      sensitive current (normalized to cell capacitance) increased with postnatal age
      in HMs that responded in a typical manner, suggesting that expression of the TRH
      sensitive conductance is also developmentally regulated. Together, these data
      indicate that the TRH raphe neuronal system of the rat brainstem is not fully
      mature at the time of birth but develops over the first few postnatal weeks. This
      was true of levels of TRH mRNA in caudal raphe nuclei, density of TRH-IR fibers
      and 3H-methyl-TRH binding in nXII, and also the manner and magnitude of
      electrophysiological responses of HMs to exogenously applied TRH.

PMID- 8301364
TI  - Reactive astrogliosis in the neonatal mouse brain and its modulation by
      cytokines.
AB  - Reactive astrogliosis is a characteristic response of astrocytes to inflammation
      and trauma of the adult CNS. To assess the hypothesis that cytokines from
      inflammatory mononuclear cells that accumulate around lesion sites have a role in
      modulating astrogliosis, this study sought to take advantage of the neonatal
      system in which astrogliosis is reported to be minimal following injury and in
      which the immune system is relatively immature compared to adult animals. A
      nitrocellulose membrane implant into the cortex of postnatal day 3 mice resulted
      in a tremendous astrogliotic response 4 d later, as measured by glial fibrillary
      acidic protein (GFAP) immunoreactivity and GFAP content. In contrast, a neonatal
      stab wound produced limited astroglial response when compared to the adult stab
      wound. Utilizing the neonatal stab wound model, cytokines were microinjected into
      the wound site at the time of injury. All cytokines tested (gamma-IFN, IL-1, IL
      2, IL-6, TNF-alpha, and M-CSF) resulted in a significantly increased
      astrogliosis. The specificity of the cytokine response was demonstrated by the
      inability of human gamma-IFN, but not mouse gamma-IFN, in enhancing neonatal
      mouse astrogliosis, in accordance with reports that the interaction of gamma-IFN
      with its receptor occurs in a species-specific manner. We conclude that neonatal
      astrocytes can become reactive if an adequate injury stimulus is presented, and
      that the release of immunoregulatory cytokines by cells around lesion sites may
      be a mechanism that contributes to the production of gliosis.

PMID- 8301365
TI  - Microtubule-associated protein 1b (MAP1b) is concentrated in the distal region of
      growing axons.
AB  - Microtubule-associated protein 1b (MAP1b) is expressed at especially high levels
      in neurons actively extending axons, and although it appears to be required for
      axon growth, the nature of its role is unknown. We reasoned that a detailed
      description of the localization of MAP1b in growing axons would help define how
      MAP1b participates in axon growth. Therefore, we have stained cultured
      sympathetic neurons with various antibodies against MAP1b, and then used digital
      image processing and analysis procedures to quantify MAP1b distribution,
      phosphorylation and association with microtubules (MTs) in actively elongating
      axons. MAP1b is present on MTs all along the axon. Quantitative analyses showed
      that MAP1b has a nonuniform distribution along growing axons. It is present at
      relatively low and constant levels along the axon shaft until approximately 130
      microns from the axon tip, where the amount of MAP1b begins to increase sharply
      and reaches a peak close to the growth cone. The peak amount of MAP1b in the
      distal axon is an order of magnitude greater than the average amount in the axon
      shaft. The enrichment of MAP1b in the distal axon was observed for total MAP1b
      and assembled MAP1b, and was even more pronounced for phosphorylated MAP1b. This
      distribution pattern remains after correcting the relative amount of MAP1b along
      the axon for variations in axonal volume. Thus, the concentration of MAP1b in the
      distal axon exceeds by severalfold that in the rest of the axon. The amount of
      assembled MAP1b relative to the amount of MT polymer also varies along the axon,
      and is greatest distally near the growth cone. This pattern of MAP1b localization
      in axons focuses attention on the distal axon and growth cone as the principal
      sites of MAP1b function in axon growth. We discuss the possibility that MAP1b
      regulates MT dynamics in the distal axon so that it is properly coordinated with
      growth cone events involved in axon extension.

PMID- 8301366
TI  - Emetic reflex arc revealed by expression of the immediate-early gene c-fos in the
      cat.
AB  - The organization of the central neuronal circuitry that produces vomiting was
      explored by mapping the distribution of c-fos protein (Fos)-like immunoreactivity
      (FLI) as a monitor of functional activity. The brainstem and spinal cord were
      examined in cats administered multiple emetic drugs (cisplatin, lobeline,
      protoveratrine, naloxone, apomorphine) or control saline injections. Some animals
      were decerebrated, paralyzed, and artificially ventilated to avoid possible Fos
      expression induced by sensory feedback or fluid depletion during vomiting.
      Fictive vomiting was identified in these animals by a characteristic pattern of
      respiratory muscle nerve (phrenic and abdominal) coactivation. Tissues were
      immunoprocessed using an antibody raised against amino acids 1-131 of Fos and the
      avidin-biotin peroxidase complex method. Enhanced nuclear FLI was observed in
      experimental animals along portions of the sensorimotor emetic reflex arc,
      including the nodose ganglia, area postrema, nuclei of the solitary tract
      (especially medial and subpostrema subnuclei), intermediate reticular zone of the
      lateral tegmental field, nucleus retroambiguus, C2 inspiratory propriospinal cell
      region, and dorsal vagal and phrenic motor nuclei. Enhanced FLI was also detected
      in the raphe magnus, subretrofacial nucleus, and spinal dorsal horn. Regions
      showing no recognizable differences in FLI between experimental and control
      animals included the vestibular, cochlear, spinal trigeminal, subtrigeminal, and
      lateral reticular nuclei. Only minor differences were observed in the
      distributions of FLI between intact and decerebrate animals. No unique, well
      defined group of labeled neurons that might function as a "vomiting center" could
      be identified. Instead, the pattern of c-fos expression suggests that neurons
      involved in coordinating the emetic response may radiate from the area postrema
      and nucleus of the solitary tract to an arc in the lateral tegmental field
      implicated in somato-autonomic integration.

PMID- 8301367
TI  - Neuronal acetylcholine receptors that bind alpha-bungarotoxin mediate neurite
      retraction in a calcium-dependent manner.
AB  - Neuronal membrane components that bind alpha-bungarotoxin with high affinity have
      only recently been shown unambiguously to function as nicotinic receptors.
      Activation of the receptors increases intracellular levels of free calcium in
      neurons. In the chick ciliary ganglion, where the receptors have been studied in
      some detail, they have been shown to have a predominantly nonsynaptic location on
      neurons and may be concentrated on pseudodendrites emerging from the somata. This
      has raised questions about the physiological significance of the receptors for
      the neurons. Here we show that activation of the receptors on isolated ciliary
      ganglion neurons in cell culture produces neurite retraction. Focal application
      of either nicotine or ACh at low concentrations induces the retraction, and alpha
      bungarotoxin blocks the effect. The retraction requires external calcium and is
      confined to the individual neurite stimulated with agonist. Brief exposure to
      elevated concentrations of K+ also induces neurite retraction, and both the K(+)
      induced and the nicotine-induced retractions can be prevented by the calcium
      channel blocker omega-conotoxin. The results suggest that activation of the alpha
      bungarotoxin-binding nicotinic receptors on neurites triggers activation of
      voltage-gated calcium channels presumably by depolarizing the membrane, and that
      together they permit sufficient calcium to enter the neurite to prevent further
      outgrowth and induce retraction.

PMID- 8301368
TI  - A functional anatomical analysis of central pathways subserving the effects of
      interleukin-1 on stress-related neuroendocrine neurons.
AB  - Systemic administration of the cytokine interleukin-1 (IL-1) results in increased
      secretion of ACTH and corticosterone in rats. The available evidence suggests
      that the acute effects of IL-1 are exerted ultimately at the level of the
      hypothalamus to increase corticotropin-releasing factor (CRF) secretion into the
      hypophyseal portal circulation, and hence the central drive on the pituitary
      adrenal system. However, the route(s) and mechanism(s) by which circulating IL-1
      gains access to central mechanisms governing pituitary-adrenal output remain
      poorly understood. In this study, we show that intravenous injection of IL-1 beta
      provokes time- and dose-dependent increases in the expression of the immediate
      early gene c-fos, in identified CRF and oxytocin-producing cells of the
      paraventricular nucleus of the hypothalamus (PVH). Several cell groups known to
      be involved in central visceromotor regulation also displayed comparable time-
      and dose-related activation to systemic IL-1, including the bed nucleus of the
      stria terminalis, the central nucleus of the amygdala, the lateral parabrachial
      nucleus, and cell groups of the dorsomedial and ventrolateral medulla. Activation
      of circumventricular organs, which have been hypothesized to serve as central
      monitors of circulating IL-1, required doses roughly an order of magnitude above
      those required to activate CRF neurons in the PVH. Combined immunohistochemical
      and retrograde tracing experiments revealed many IL-1-responsive cells in the
      nucleus of the solitary tract and the ventrolateral medulla to be
      catecholaminergic and to project to the region of the PVH. Discrete and
      unilateral interruption of ascending catecholaminergic projections from the
      medulla attenuated IL-1-stimulated increases in Fos immunoreactivity and CRF mRNA
      in the PVH on the ipsilateral side. Disruption of descending projections from
      circumventricular structures associated with the lamina terminalis did not affect
      IL-1-mediated Fos induction in the PVH. We conclude that medullary
      catecholaminergic projections to the PVH play either a mediating or a permissive
      role in the IL-1-induced activation of the central limb of the hypothalamo
      pituitary-adrenal axis.

PMID- 8301369
TI  - Treatment of carotid-cavernous fistula by trans-venous anterior (trans-orbital)
      approach. Case report and review of previous report.
AB  - A case is reported of successful occlusion of a dural carotid-cavernous fistula
      (type D) by means of a transvenous anterior approach. Through the left angular
      vein, the distal superior ophthalmic vein (SOV) and the cavernous sinus were
      cannulated and three Gianturco coils were delivered close to the fistulous
      communications. Obliteration of the carotid-cavernous communication was achieved
      sparing the internal carotid artery and its branches. The major advantage of
      entering the sinus from the venous route is to preclude any damage to the artery,
      distal migration of the detachable balloon or of thrombi, intracavernous
      pseudoaneurysm formation. The trans-orbital approach may be considered chiefly
      when the openings are in the antero inferior compartment and the SOV is enlarged.
      Its applications, quite sporadic until now, probably will become more popular,
      mainly in treating D type fistulas, thanks to the good results achieved and to
      its safety.

PMID- 8301370
TI  - Associated chronic subdural haematoma and meningeal neoplasm. Two case reports.
AB  - The authors present two cases of non-traumatic subdural haematomas associated
      with a meningioma. Relevant literature is reviewed and the pathogenesis of this
      rare condition is discussed.

PMID- 8301371
TI  - Hemangioendothelioma mimicking a median nerve neoplasm. Case report.
AB  - The authors report a case of brachial vein epithelioid hemangioendothelioma
      resembling a median nerve neoplasm clinically and radiologically. It was found as
      a mass closely attached to median nerve and arising from one of two brachial
      veins. Simple resection, requiring sacrifice of the vein, allowed nerve median
      sparing but recurrence occurred one year later. Hemangioendothelioma should be
      also considered in differential diagnosis and in the planning surgery of arm
      median nerve masses. Wide local excision is surgical treatment recommended in
      those cases when regional lymph nodes or systemic metastasis have not been
      recognized. Regional lymph nodes resection and adjunctive radiation and chemo
      therapy should be considered only for "malignant" or metastatic
      hemangioendothelioma.

PMID- 8301372
TI  - Thrombolysis in cerebral ischemia. A review of clinical and experimental data.
AB  - Thrombolytic therapy has been proposed in the treatment of cerebrovascular
      occlusive disease. Early clinical experiences with Urokinase and Streptokinase
      raised concern about the risk of hemorrhagic complications. More recently, tissue
      plasminogen activator (tPA) has been evaluated experimentally with promising
      results. Its clinical utilization has been recently initiated. A review of
      experimental and clinical data on thrombolysis in cerebral ischemia is presented.
      TPA treatment produced recanalization and clinical improvement in several
      patients. The rate of intracranial hemorrhagic complications is similar to the
      incidence of spontaneous hemorrhagic conversion of ischemic infarction.
      Nevertheless, large placebo-controlled clinical trials are necessary to further
      define the efficacy and the optimal modality of administration of tPA in
      thromboembolic stroke.

PMID- 8301373
TI  - Intracisternal rt-PA during early surgery for aneurysmal subarachnoid hemorrhage:
      an Italian report.
AB  - A patient undergoing surgery within 24 hours of aneurysm rupture was administered
      recombinant tissue plasminogen activator (rt-PA) directly into the basal
      subarachnoid cisterns after aneurysm clipping. Preoperatively, the patient had
      diffuse thick subarachnoid blood clots on CT. The rt-PA was given as a single
      injection of 10 mg. Postoperatively the patient was evaluated by serial CT scans
      and daily transcranial Doppler (TCD) examinations. An almost complete clot
      clearance was demonstrated on CT scans carried out on day 2 and day 4 after
      surgery. TCD studies failed to show any acceleration of blood flow velocity
      indicative of vasospasm. The postoperative curse was uneventful, without any
      clinical indication of delayed ischemia and no evidence of progressive
      hydrocephalus. Considering the data of the literature, as well as our initial
      experience, it appears that intracisternal thrombolysis with rt-PA can be
      achieved with relative safety and is effective for large-volume subarachnoid
      blood collections removal and vasospasm prevention. Results from open trials
      recently published suggest that a substantial advance in the management of an
      important subgroup of patients with aneurysmal subarachnoid hemorrhage (SAH) may
      be in the offing. However, randomized, placebo-controlled trials are still needed
      to confirm that there is a well-definite clinical benefit from the use of rt-PA.
      These considerations now call for a nation-wide multicentric italian trial which
      should be also addressed to evaluate other dose regimens and modalities of
      application.

PMID- 8301374
TI  - Auditory middle latency responses in patients with intracranial space-occupying
      lesions.
AB  - Auditory middle latency responses (MLRs) and auditory brainstem responses (ABRs)
      were investigated pre- and postoperatively in three patients operated on of
      intracranial tumor (craniopharyngioma in cases 1 and 2, left-temporal cystic
      astrocytoma in case 3). In each case examined, preoperative MLRs were informative
      in evaluating the damage to supratentorial neural structures owing to the tumor;
      furthermore, they allowed a precious evaluation of the functional integrity of
      these structures after surgery. Likewise, in case 2 the ABRs indicated a
      brainstem injury secondary to overzealous manipulation of the right temporal
      lobe. Finally, in case 3, the most prominent complex of the MLRs, ie Na-Pa, was
      abnormal both before and after intervention; indeed, in pre- and postoperative
      MLRs, Na could be identified in both ears, whereas Pa was greatly reduced in
      amplitude or absent: this finding would seem to suggest that Na and Pa have
      different generator sites.

PMID- 8301375
TI  - Intracarotid cisplatin chemotherapy for high-grade astrocytomas.
AB  - Twenty-five patients with malignant astrocytomas (grade III and IV) were treated
      with intraarterial infusions of cisplatin at 4/8 weeks intervals. Of the 23
      evaluable patients, none had a complete response, 1 (4.3%) had a probable
      response (unequivocal improvement in the neurological examination and CT evidence
      of a decrease in tumor size), 15 (65.2%) had stable disease, and 7 (30.5%) had a
      progression (unequivocal worsening of both the neurological examination and the
      CT scan). Twenty-one of the 25 patients exhibited some degree of toxicity; the
      only two serious complications observed were neurological and retinal.

PMID- 8301376
TI  - Epilepsy and low grade gliomas in pediatric neurosurgery.
AB  - A series of 33 children affected by low grade gliomas and epilepsy is reported.
      Seizures are often the only symptom of these patients; intracranial hypertension
      and focal neurological signs may be present too. All children were operated on;
      tumor removal was performed in 21 cases, tumor removal associated with
      corticectomy and/or lobectomy was performed in 12 patients. The treatment of
      epilepsy has been more effective in the first group of patients with only
      lesionectomy than in the second one, in which neoplasm removal was coupled with
      nervous system tissue asportation.

PMID- 8301377
TI  - Spinal ependymomas and papilledema: report of 4 cases and review of the
      literature.
AB  - We report 4 cases of ependymoma of the filum terminale with associated
      intracranial hypertension syndrome. After analyzing the relevant published work,
      we consider the possible pathogenetic hypotheses for this rare association.

PMID- 8301378
TI  - A framework for the development of nurse manager negotiation skills.
AB  - Effective negotiation skills have been identified as an essential component of
      the nurse manager role. Application of the negotiation process in today's dynamic
      and competitive health care environment is frequently difficult and stressful for
      the novice nurse manager. The authors describe a Conceptual Model for Negotiation
      that can be used as a management development framework for the novice nurse
      manager.

PMID- 8301379
TI  - Decentralization and the nurse educator: research, responsibilities, and
      barriers.
AB  - Decentralization is increasingly used in departments of nursing to achieve such
      outcomes as cost containment, job satisfaction, and improved patient care.
      Because decentralization is considered invaluable in today's rapidly changing
      health care environment, nurse educators must be knowledgeable regarding its
      principles and barriers. Their educational role and their support of staff during
      the transition period are critical to successful implementation.

PMID- 8301380
TI  - The nurse internship experience: a dynamic learning environment for the novice.
AB  - This article highlights the history of nurse internship programs and reviews the
      application process, the content, and the design of a nurse internship program.
      The program described has proven to be a developmental process for the nurse
      intern, the preceptor, and the staff development specialist. Recommendations are
      presented for implementation of a successful nurse internship program.

PMID- 8301381
TI  - Research utilization: making the link to practice.
AB  - One goal of nursing staff development educators is to update staff practice
      through the application of nursing research findings. A multi-site study was
      conducted to determine what factors are related to a nurse's use of research
      findings. The study suggests that staff involvement in research-related
      activities such as data collection is the best predictor of use of research
      findings in the clinical setting. This finding was used to design strategies for
      facilitating the transfer of research findings to practice.

PMID- 8301382
TI  - Educational implications of nurses' brain dominance, learning styles, and
      attitudes toward computerization.
AB  - Nurses have been described as exhibiting computer anxiety as hospitals become
      automated. Suggestions have been made to provide inservice education to decrease
      computer anxiety before systems installation. This study examined nurses' brain
      dominance profiles, learning styles, and attitudes toward computers. Results
      indicated that 95 staff nurses had 14 different learning styles and were willing
      to use computers to document nursing care. As hospital inservice education
      programs are developed, a variety of teaching-learning methods needs to be
      developed to facilitate learning this new technology.

PMID- 8301383
TI  - The role of the off-shift educator.

PMID- 8301384
TI  - A Renal Jeopardy game.

PMID- 8301385
TI  - Data management ... record keeping.

PMID- 8301386
TI  - To start writing, try a book review.

PMID- 8301387
TI  - Use of the Myers-Briggs Type Indicator to develop a continuing education
      department.
AB  - Myers-Briggs concepts are useful for understanding and managing individual and
      group strengths, preferences, and "blind spots." Requirements of the work to be
      accomplished can be matched to the strengths and preferences of the individual or
      group. Work groups can be selected to enhance individual strengths and to
      counterbalance blind spots. This article describes the experience of one hospital
      based continuing education department that uses the Myers-Briggs Personality
      Trait Inventory to explore department members' strengths and preferences.
      Understanding individual preferences has helped group members to understand,
      anticipate, and work with one another. The ideal mix of profiles challenges and
      stimulates both the individual and the department. Maximizing diversity increases
      the potential for conflict between individuals with opposite preferences;
      recognizing strengths and blind spots, willingness to talk about work style
      differences, and a little humor all make peaceful coexistence possible.

PMID- 8301388
TI  - The real values of partnership. Preventing professional amorphism.

PMID- 8301389
TI  - A time to listen--staff and manager views on education, practice, and management.

PMID- 8301390
TI  - Privacy and confidentiality of patient information. Challenges for nursing.
AB  - The growing interest in automating healthcare information and the emergence of
      the computer-based patient record-keeping have brought the issues of privacy and
      confidentiality to the fore-front. Nurse executives and nurse managers need to be
      sensitive to these issues, as never before, to guide their staffs and to prevent
      harm. Technology makes sensitive information more accessible to more people, with
      resulting benefits and dangers. The author presents a nursing ethical framework
      for discussing patient privacy and confidentiality issues, and highlights
      specific issues that reflect nursing's unique viewpoints.

PMID- 8301391
TI  - Behind closed doors. What the nurse executive should know about surgical
      services.
AB  - Many nurse executives have never worked in the operating room (OR) and are often
      told they "don't understand" by the surgical services director. Often, nurse
      executives do not have the surgical background required to make informed
      decisions about problems associated with surgical services. The authors provide
      insight into issues that exist in the OR environment and present strategies for
      improving nurse executives' relationships with the OR staff, management, and
      surgeons.

PMID- 8301392
TI  - Nursing case management activities. How they differ between employment settings.
AB  - The diversity of case management approaches raises many questions. Are multiple
      case managers really required to duplicate each others' services, and if so, to
      what degree? How does the case manager actually "case manage" a client? How do
      the activities of the case manager in a direct care environment differ from case
      managers employed by case management companies or insurance companies? In this
      article, the author describes differences in case management activities in
      various employment settings.

PMID- 8301393
TI  - Rural magnet hospitals of excellence. Part 2.
AB  - Although almost half of the hospitals in the United States are rural and small,
      they often are not seen as leaders in innovation. However, many practices now
      being adopted by large hospitals have been used in rural hospitals for many
      years. To understand excellence in rural hospitals, the authors present a study
      of rural hospitals of excellence, using procedures from the 1982 Magnet Hospitals
      Study. Part 1 was reported in the January issue of JONA.

PMID- 8301394
TI  - Motivation to join or reject unions.

PMID- 8301396
TI  - Organizational transformation for the future.

PMID- 8301395
TI  - The clinical ladder. Impact on nurse satisfaction and turnover.
AB  - Nurse administrators have advocated clinical ladder programs to address salary
      compression of experienced nurses. However, few clinical ladder programs have
      survived the test of time. One possible explanation for the demise of these
      programs is the failure to assess nurses' satisfaction with clinical ladder
      programs. Ongoing assessment of these programs may provide a solution to early
      demise.

PMID- 8301397
TI  - Vision, hallucinations, and wannabes, Part 2.

PMID- 8301398
TI  - The Chief Nurse Officer as a board member--insights and experiences.

PMID- 8301399
TI  - Nature of coarse-to-fine constraints on binocular fusion.
AB  - Several stereo-matching algorithms posit that processing on coarse (low spatial
      frequency) scales constrains processing on fine (high spatial frequency) scales
      by shifting the disparity range over which fine mechanisms operate. If this were
      the case, stereo increment thresholds for high frequencies in the presence of low
      frequencies would be constant, regardless of base disparity. In contrast, we find
      that in the presence of low spatial frequencies, increment thresholds for high
      spatial frequencies increase with base disparity, as do increment thresholds for
      high frequencies presented alone. As a further test of whether information on
      coarse scales enhances processing on fine scales, diplopia thresholds were
      measured. In the presence of low frequencies, fusion ranges for high frequencies
      were severely reduced. These constraints were found to exhibit a power-law
      dependence on low frequency contrast and to operate over relatively localized
      areas of the visual field.

PMID- 8301400
TI  - Lightness and brightness judgments of coplanar retinally noncontiguous surfaces.
AB  - Several experiments reveal that judgments of lightness and brightness of an
      achromatic surface depend, in part, on the luminances of other surfaces perceived
      to share the same depth plane, even if the surfaces are well separated on the
      retina. Two Mondrians, simulated on a CRT, were viewed through a haploscope. The
      more highly illuminated Mondrian contained a comparison patch and appeared nearer
      than the more dimly illuminated Mondrian, which contained the test patch. By
      independently varying the disparity of the test patch, observers could make the
      test patch appear to be in the depth plane of either the dimly or the highly
      illuminated Mondrian. Observers set the luminance of the test patch to match that
      of the comparison patch. The test was set as high as 15% more luminous when it
      was perceived in the depth plane of the highly illuminated rather than the dimly
      illuminated Mondrian. Both brightness and lightness judgments were affected by
      the perceived depth of the test, although the lightness judgments of
      inexperienced observers sometimes were dominated by local-contrast matching.

PMID- 8301401
TI  - Appearance of colored patterns: pattern-color separability.
AB  - We have measured how color appearance of square-wave bars varies with stimulus
      strength and spatial frequency. Observers adjusted the color of a uniform patch
      to match the color appearance of the bars in square-wave patterns. We used low-to
      moderate square-wave patterns, from 1 to 8 cycles per degree (c/deg). The matches
      are not photoreceptor matches but rather are established at more central neural
      sites. The signals at the putative central sites obey several simple
      regularities. The cone contrast of the uniform patch is proportional to square
      wave stimulus strength (color homogeneity) and additive with respect to the
      superposition of equal-frequency square waves containing different colors (color
      superposition). We use the asymmetric matches to derive, from first principles,
      three pattern-color-separable appearance pathways. The matches are explained by
      two spectrally opponent, spatially low-pass mechanisms and one spectrally
      positive, spatially bandpass mechanism. The spectral mechanisms that we derive
      are similar to luminance and opponent mechanisms that are derived with entirely
      different experimental methods.

PMID- 8301402
TI  - Isolation of the middle- and long-wavelength-sensitive cones in normal
      trichromats.
AB  - Spectral sensitivity in the red-green spectral range typically reflects the joint
      influence of the middle-wavelength-sensitive cones (the M or green cones) and
      long-wavelength-sensitive cones (the L or red cones). The balance of M- and L
      cone influence can be altered by presenting the test lights superimposed upon
      steady background fields of long or short wavelength. We find that presenting
      test stimuli just after an abrupt exchange between two colored backgrounds
      permits an easier and closer approach to cone isolation than presenting them
      either on a steady background or following an intense bleach. Background exchange
      drives the flicker detection or flicker photometric spectral sensitivities
      measured at 17 Hz to a limiting condition at lower intensities than do steady
      backgrounds. This condition is consistent with either M- or L-cone isolation.
      Steady backgrounds do not produce complete cone isolation: even on backgrounds
      that push spectral sensitivity closest to M or L, there are substantial phase
      differences between flickering lights of different color. In contrast, no phase
      differences remain following background exchange. The improvement in cone
      isolation produced by the exchange procedure is not confined to flicker
      measurements: the spectral range over which subjects are temporarily
      monochromatic is more extended following background exchange than on steady
      fields.

PMID- 8301403
TI  - Spectral sensitivities of the human cones.
AB  - Transient chromatic adaptation produced by an abrupt change of background color
      permits an easier and closer approach to cone isolation than does steady-state
      adaptation. Using this technique, we measured middle-wave-sensitive (M)-cone
      spectral sensitivities in 11 normals and 2 protanopes and long-wavelength
      sensitive (L-) cone spectral sensitivities in 12 normals and 4 deuteranopes.
      Although there is great individual variation in the adapting intensity required
      for effective isolation, there is little variation in the shape of the M- and L
      cone spectral-sensitivity functions across subjects. At middle and long
      wavelengths, our mean spectral sensitivities agree extremely well with
      dichromatic spectral sensitivities and with the M- and L-cone fundamentals of
      Smith and Pokorny [Vision Res. 15, 161 (1975)] and of Vos and Walraven [Vision
      Res. 11, 799 (1971)], both of which are based on the CIE (Judd-revised) 2 degrees
      color-matching functions (CMF's). But the agreement with the M-cone fundamentals
      of Estevez [Ph.D. dissertation, Amsterdam University (1979)] and of Vos et al.
      [Vision Res. 30, 936 (1990)], which are based on the Stiles-Burch 2 degrees
      CMF's, is poor. Using our spectral-sensitivity data, tritanopic color-matching
      data, and Stile's pi 3, we derive new sets of cone fundamentals. The consistency
      of the proposed fundamentals based on either the Stiles-Burch 2 degrees CMF's or
      the CIE 10 degrees large-field CMF's with each other, with protanopic and
      deuteranopic spectral sensitivities, with tritanopic color-matching data, and
      with short-wavelength-sensitive (S-) cone spectral-sensitivity data suggests that
      they are to be preferred over fundamentals based on the CIE 2 degrees CMF's.

PMID- 8301404
TI  - Quality improvement processes applied to infusion nursing practice.
AB  - With the current emphasis in healthcare delivery on patient outcomes and quality
      care, infusion therapy nurses and managers must use effective quality improvement
      processes. This article reviews the terminology associated with the quality
      improvement processes, provides a brief overview of methods for identification of
      "quality improvement areas" in infusion therapy activities, and offers monitoring
      examples for those who are evaluating quality care delivery.

PMID- 8301405
TI  - A comparison of patient-controlled analgesia versus traditional intramuscular
      analgesia in postoperative pain management.
AB  - A retrospective chart review of the 198 postoperative subjects (patient
      controlled analgesia [PCA] group = 100 and non-PCA group = 98) comparing
      analgesic usage and other variables was conducted. The PCA group used
      significantly more medication during the first 24 hours postoperatively and
      patients required more analgesic when a greater number of secondary diagnoses
      existed. No significant differences were found in length of stay or
      documentation.

PMID- 8301406
TI  - Implementation of a customized needleless intravenous delivery system.
AB  - Occupational exposure to human immunodeficiency virus (HIV), hepatitis, and other
      bloodborne pathogens concerns all health care workers, especially those in high
      risk clinical settings such as the emergency room, operating room, intravenous
      therapy department, etc. In response to the increased attention to needlestick
      injuries in the workplace, hospitals are adopting a more proactive approach to
      establishing precautions to eliminate this occupational hazard. Many technologies
      to address the situation are available today, but most offer only a partial
      solution. The need for a comprehensive needleless IV delivery system recently
      sparked a collaboration between the IV therapy coordinator and a manufacturer's
      representative (Abbott Laboratories) that resulted in a new product design that
      was recently implemented house wide at our two hospitals.

PMID- 8301407
TI  - Chapter scholarship development.
AB  - The Great Lakes Chapter of the Intravenous Nurses Society developed a scholarship
      program to reward members for participation in INS activities and to promote the
      INS goals of education and knowledge sharing. Scholarships were awarded for
      holding office or committee work, educational activities or authorship, meeting
      attendance and recruitment efforts, and certification/recognition by INS. This
      article describes the point system used for awarding scholarships, program
      funding, and pitfalls in the program.

PMID- 8301408
TI  - Photochemical interactions of methylene blue and analogues with DNA and other
      biological substrates.
AB  - The light-induced reactions of methylene blue and related phenothiazinium dyes
      with biological substrates are described. The properties of the excited states of
      the dyes, their reactions with nucleic acids and their photosensitised chemical
      modifications of nucleic acid bases are examined. Reports on phenothiazinium dye
      induced damage to proteins, lipids, biological membranes, organelles, viruses,
      bacteria, mammalian cells and carcinomas are reviewed.

PMID- 8301409
TI  - DNA cleavage, antiviral and cytotoxic reactions photosensitized by simple
      enediyne compounds.
AB  - Very potent antibiotic antitumor natural products contain a enediyne moiety
      which, upon thermal activation, is capable of abstracting hydrogens from DNA. 1,6
      Diphenyl-3-hexene-1,5-diyne was selected as a candidate for inducing DNA strand
      breaks photochemically. Easily interconverted with light, both geometric isomers
      1 and 2 were expected to be phototoxic. As anticipated, they photosensitized the
      production of strand breaks in double-stranded supercoiled pBR322, and in single
      stranded M13 DNA. The DNA cleavage reactions were favored by the presence of
      oxygen and were inhibited by ethanol. Preliminary experiments with the (Z)-isomer
      indicated moderate light-dependent antiviral activity against human
      immunodeficiency virus (HIV), Sindbis virus, and mouse cytomegalovirus. The
      enediynes were cytotoxic to Escherichia coli, a gram-negative organism, to
      Streptococcus faecalis, a gram-positive organism, to Daphnia magna and to fish
      (Pimephales promelas), but only in the presence of light. The production of o
      terphenyl, the expected product of Bergman cyclization of 1, could not be
      confirmed. However, both 1 and 2 photosensitized the formation of singlet oxygen
      and of superoxide anion radical, and photodynamic reactions could have been
      responsible for some of the phototoxic reactions observed.

PMID- 8301410
TI  - Time-resolved in-vivo fluorescence of photosensitizing porphyrins.
AB  - Various components of photosensitizing porphyrins (e.g. monomers, aggregates,
      ionic species) have been recently localized in single cells by time-resolved
      fluorescence microscopy. Novel time-resolving techniques, based on picosecond
      laser diodes, a frequency-doubled Nd:YAG laser and time-gated microscopic
      equipment, were used for in-vivo measurements of the chick chorioallantoic
      membrane (CAM) exhibiting a pronounced vasculature. Changes of the fluorescence
      decay kinetics after light exposure were correlated with the formation of a
      photoproduct (Photosan, aminolaevulinic acid) or changes of the intracellular
      binding sites (tetraphenyl-porphyrins). Fluorescent components with different
      decay times were shown to be distributed differently within the tissue.

PMID- 8301411
TI  - Combination therapy: photochemotherapy; electric current; and ionizing radiation.
      Different combinations studied in a WiDr human colon adenocarcinoma cell line.
AB  - The interactions of pairs of the modalities Photofrin II-sensitized
      photochemotherapy (PCT), ionizing radiation and an electric current were
      investigated by the colony formation assay in WiDr cells, a human colon
      adenocarcinoma cell line. When the cells were treated simultaneously with PCT and
      an electric current, a slightly synergistic effect was observed at low exposures
      (surviving fraction approximately 0.1) while a seemingly antagonist effect was
      found at higher exposures. The same was found to be true for the combinations of
      PCT plus ionizing radiation and ionizing radiation plus electric current.

PMID- 8301413
TI  - An EPR spin trapping study of albumin protein radicals formed by the photodynamic
      action of haematoporphyrin.
AB  - The photodynamic action of haematoporphyrin (8,13-bis (1-hydroxyethyl)-3,7,12,17
      tetramethyl-21H,23H-porphine-2,18 -dipropionic acid) has been shown to generate
      radical species upon isolated bovine and human serum albumins by the detection,
      using EPR spectroscopy, of adducts of the protein-derived radicals to spin traps.
      Similar radicals can also observed with fresh human serum, suggesting that
      similar species might be generated during in vivo photodynamic therapy. These
      radicals are believed to arise as a result of processes both dependent and
      independent of singlet oxygen formation (Type II and Type I reactions
      respectively). The formation of these protein radicals can be inhibited by
      physiologically relevant antioxidants such as glutathione and ascorbate in a dose
      dependent manner; the observation of similar species with fresh serum does
      however suggest that these defensive processes can be easily overwhelmed. The
      relevance of these findings to the photodynamic therapy of tumours is discussed.

PMID- 8301412
TI  - Liposome-delivered Zn(II)-2,3-naphthalocyanines as potential sensitizers for PDT:
      synthesis, photochemical, pharmacokinetic and phototherapeutic studies.
AB  - The aim of this investigation is to report the synthesis and fundamental
      photochemical properties of naphthalocyanines with potential interest for
      photodynamic therapy (PDT), as well as their pharmacokinetics and
      phototherapeutic effects in a tumor model. Four zinc naphthalocyanines (ZnNc),
      unsubstituted ZnNc 1, tetraacetylamido-substituted ZnNc 2, tetraamino-substituted
      ZnNc 3 and tetramethoxy-substituted ZnNc 4 absorbing around 760-770 nm, were
      synthesized. The dye-sensitized photo-oxidation of 1,3-diphenylisobenzofuran via
      1O2 was studied in dimethylsulfoxide (DMSO). Quantum yields for this
      photoreaction are 0.135-0.164 and are relatively independent of the kind of
      substituent. In addition, the photoinduced electron transfer studied in N,N
      dimethylformamide-water in the presence of methylviologen and mercaptoethanol is
      only slightly influenced by the kind of substituent. The pharmacokinetic
      properties of ZnNc 1 in hamsters bearing a transplanted rhabdomyosarcoma were
      studied using dipalmitoylphosphatidylcholine liposomes. Experimental PDT of
      rhabdomyosarcoma was carried out using liposome-delivered ZnNc 1-4. The
      phototherapeutic effect was evaluated by tumor photonecrosis, the mean tumor
      diameter during the observation period and the percentage of cured animals. The
      best effect was found after PDT with ZnNc 2 (50% of the treated animals were
      cured). A slightly lower effect was observed after application of ZnNc 4 (40%
      cured animals). No effect at all was noted after PDT with ZnNc 3 and a very low
      efficiency was found after treatment with ZnNc 1 as photosensitizer. Obviously,
      the photodynamic effect depends on the biological characteristics as well as on
      the nature of the substituents.

PMID- 8301414
TI  - Urea unfolding and stability of gamma-II crystallin.
AB  - The conformational stability of gamma-II crystallin at pH 7.0 was estimated by
      studying its urea denaturation at isothermal conditions. The conformational
      states were monitored by far UV-CD and fluorescence measurements. Gamma-II
      crystallin shows sigmoidal order-disorder transition curves by both methods. The
      presence of more than one intermediate was confirmed but at neutral pH. The
      experiment results were critically analyzed in terms of both linear extrapolation
      and Tanford's models. The Gibbs free energy of unfolding delta G u,H2O = -36 kcal
      mol-1 was obtained. This value corresponds to the high conformational stability
      of the protein predicted qualitatively by its crystal structure.

PMID- 8301415
TI  - Photoreactions of riboflavin with spermine and their role in tryptophan
      photoconsumption induced by riboflavin.
AB  - The influence of spermine (Spr) on riboflavin (Rb) and riboflavin-tryptophan (Rb
      Trp) solutions irradiated at 450 nm under aerobic and anaerobic conditions was
      studied. In both systems, it is shown that Spr interacts with 3Rb probably giving
      spermine-derived and flavin-derived radicals. In the presence of oxygen, modified
      Rb is regenerated with the simultaneous production of the active oxygen species
      O2.- and/or HO2.. The addition of Spr to the Rb-Trp system under aerobic
      conditions leads to a small protection of Trp consumption, although oxygen
      consumption is increased. This small protection arises as a consequence of
      competitive interaction of Trp and Spr with 3Rb. The competition of Spr and
      oxygen for 3Rb could also explain the autocatalytic oxygen consumption observed
      in the presence of the amine. Under anaerobic conditions Spr produces a larger
      protection of Trp consumption, which is compatible with the larger Rb triplet
      lifetime expected under these conditions.

PMID- 8301416
TI  - Two-photon ionisation of the antitumor drug pazelliptine (BD40) by 355 nm laser
      photolysis.
AB  - The effect of 2 ns pulses of 355 nm laser light on aqueous solutions of
      pazelliptine (PZE) was investigated and biphotonic ionization was observed. The
      absorption spectrum corresponding to the pazelliptine radical cation (PZE+) and
      the hydrated electron simultaneously formed in this process was determined. In
      the absence of oxygen, eaq- reacted with unexcited PZE (k = 1.6 x 10(10) M-1 s-1)
      to give the pazelliptine radical anion (PZE-). This latter species was identified
      by separate pulse radiolysis experiments. The radicals cation and anion
      disappeared by recombination on the millisecond time range. In presence of
      oxygen, eaq- was scavenged by O2 leading to the formation of the superoxide
      radical (O2.-) in competition to the formation of the radical PZE.-.PZE+ reacted
      with O2.- to produce H2O2 (k = 9 x 10(9) M-1 s-1). The spectral analysis revealed
      that PZE triplet was also formed during the laser pulse. In the absence of
      oxygen, the triplet-triplet absorption decreased on the microsecond time scale
      (2k = 1.5 x 10(10) M-1 s-1). In oxygenated solutions, eaq- and the pazelliptine
      triplet decayed exponentially in the same time range.

PMID- 8301417
TI  - Singlet oxygen yields of furocoumarins and related molecules--the effect of
      excitation wavelength.
AB  - Singlet oxygen yields (phi delta) were compared for a wide range of furocoumarins
      and related compounds using excitation wavelengths of 313, 334 and 365 nm. The
      phi delta values ranged from 0.02 or less to 0.4, but no wavelength dependence
      was detected for any of the compounds studied.

PMID- 8301418
TI  - Cytotoxicity of UV-oxidized LDL to cultured cells. A model system for studying
      the potential role of toxic events in atherosclerosis.

PMID- 8301419
TI  - Local anesthetics in the management of acute pain in children.

PMID- 8301420
TI  - Outcome measures for clinical trials in cystic fibrosis. Summary of a Cystic
      Fibrosis Foundation consensus conference.
AB  - The CFF Consensus Conference concluded with a summary of those outcome measures
      that would be most useful in studies of patients 6 years of age and older and
      those measures that would be most useful in studies of the younger population (<
      6 years of age) (Table). These measures were further divided into biologic
      markers most appropriate for initial (phase I and phase II) clinical trials and
      those especially useful in large, multicenter (phase III) pivotal trials. There
      is an ongoing need to improve the accuracy and validity of currently available
      measures of biologic activity and clinical efficacy in CF, especially in the
      younger population. The conference participants recommended that the following
      eight issues be addressed as soon as possible: (1) definition of pulmonary
      exacerbation, (2) broadly applicable methods of testing pulmonary function in
      small children (ideally a single test for all ages), (3) a comprehensive severity
      of-disease score for young children, (4) reliable methods of quantifying chest x
      ray and CT scan changes in young patients, (5) simple, inexpensive measures of
      lung inflammation, (6) a centralized, uniform approach to the establishment of
      data monitoring committees, (7) a quality of well-being scale for small children,
      and (8) reliable, reproducible aerosol delivery systems with defined
      characteristics. In addition, participants recommended that better methods be
      developed for assessing patients' adherence to research protocols.

PMID- 8301421
TI  - Human milk secretory IgA antibody to nontypeable Haemophilus influenzae: possible
      protective effects against nasopharyngeal colonization.
AB  - Sixty-eight children fed human milk were followed prospectively from birth to 12
      months of age to assess the effect of milk antibody on nasopharyngeal
      colonization. Human milk secretory IgA antibody to P6, a highly conserved outer
      membrane protein of nontypeable Haemophilus influenzae, was measured with the use
      of an enzyme-linked immunosorbent assay. Nasopharyngeal colonization with
      nontypeable H. influenzae and the occurrence of otitis media were determined.
      Nasopharyngeal colonization was found in 22 children (32%), and 39 children (57%)
      had otitis media. Frequency of isolation of nontypeable H. influenzae was
      directly related to episodes of otitis media (r = 0.35; p = 0.001). The level of
      human milk anti-P6 secretory IgA antibody was inversely related to frequency of
      isolation of the organism (r = -0.27; p = 0.026). The average antibody level,
      expressed as nanograms per 0.1 mg total secretory IgA, in human milk fed to
      children with no colonization of nontypeable H. influenzae was significantly
      higher than in milk fed to children in whom colonization occurred on multiple
      occasions (156 +/- 120 vs 69 +/- 50; p = 0.013). Prevention of colonization was
      most evident during breast-feeding. These data suggest that the protective
      effects of human milk against otitis media may be due in part to inhibition of
      nasopharyngeal colonization with nontypeable H. influenzae by specific secretory
      IgA antibody.

PMID- 8301422
TI  - Infant vocalizations and the early diagnosis of severe hearing impairment.
AB  - To determine whether late onset of canonical babbling could be used as a
      criterion to determine risk of hearing impairment, we obtained vocalization
      samples longitudinally from 94 infants with normal hearing and 37 infants with
      severe to profound hearing impairment. Parents were instructed to report the
      onset of canonical babbling (the production of well-formed syllables such as
      "da," "na," "bee," "yaya"). Verification that the infants were producing
      canonical syllables was collected in laboratory audio recordings. Infants with
      normal hearing produced canonical vocalizations before 11 months of age (range, 3
      to 10 months; mode, 7 months); infants who were deaf failed to produce canonical
      syllables until 11 months of age or older, often well into the third year of life
      (range, 11 to 49 months; mode, 24 months). The correlation between age at onset
      of the canonical stage and age at auditory amplification was 0.68, indicating
      that early identification and fitting of hearing aids is of significant benefit
      to infants learning language. The fact that there is no overlap in the
      distribution of the onset of canonical babbling between infants with normal
      hearing and infants with hearing impairment means that the failure of otherwise
      healthy infants to produce canonical syllables before 11 months of age should be
      considered a serious risk factor for hearing impairment and, when observed,
      should result in immediate referral for audiologic evaluation.

PMID- 8301423
TI  - Psychosocial factors associated with the use of bicycle helmets among children in
      counties with and without helmet use laws.
AB  - We examined the extent to which psychosocial factors, in addition to the presence
      of a law, are associated with the use of bicycle helmets. A mailed questionnaire
      was completed by 3494 children in fourth, seventh, and ninth grades in three
      Maryland counties: Howard County, which had a law requiring child bicyclists to
      wear helmets and an educational campaign; Montgomery County, which had an
      educational campaign but no law; and Baltimore County, which had neither.
      Overall, 19% of the respondents reported having worn a bicycle helmet on their
      most recent ride. In a multiple logistic regression, children's use of helmets in
      all three counties was significantly associated with their beliefs about the
      social consequences of wearing helmets and the extent to which their friends wear
      helmets. Significant interactions were also found, suggesting that in the
      presence of a law, an educational campaign, or both, children's use of helmets
      was associated more with social concerns than with parental influences or
      cognitive factors, such as beliefs about the need for helmets or perceptions of
      risk. To increase helmet use, the issues of stylishness, comfort, and social
      acceptability of wearing helmets need to be addressed and more widespread
      adoption of bicycle helmet laws should be encouraged.

PMID- 8301424
TI  - Incidence of sudden infant death syndrome in infants with sickle cell trait.
AB  - The significantly higher incidence of both sickle cell trait (SCT) and sudden
      infant death syndrome (SIDS) in the black population suggests that SCT and SIDS
      may be epidemiologically related. To study this possibility, we identified, for
      the period of February 1990 to February 1992, all infants with SCT born in Los
      Angeles County whose disease was diagnosed through the California Newborn
      Screening Program. We matched these infants with all confirmed cases of SIDS in
      Los Angeles County from February 1990 to March 1993. Three cases of SCT among 589
      infants confirmed to have had SIDS were identified. The incidence of SIDS was
      1.25/1000 live births for the general population versus 0.58/1000 cases for the
      SCT group. This finding remained unchanged when rates were adjusted for
      ethnicity. We conclude that infants born with SCT are not at increased risk of
      dying of SIDS.

PMID- 8301425
TI  - Variable degrees of suppression of hemoglobin S synthesis in subjects with
      hemoglobin SS disease on a long-term transfusion regimen.
AB  - The objectives of this study were to quantify the amount of blood required to
      suppress synthesis of hemoglobin S (HbS) in patients with hemoglobin SS on a long
      term transfusion regimen and to evaluate factors that might contribute to
      variations in transfusion-induced patterns of responsiveness. Eleven patients
      with hemoglobin SS (age range, 2 years 4 months to 19 years 9 months) who had had
      a cerebrovascular accident were monitored during a period of 1 1/2 to 4 years for
      HbS percentages, reticulocyte percentages, the amount of erythrocytes infused,
      and weight. From these data the amount of blood necessary to maintain the HbS
      concentration at less than 30% was expressed as units of packed erythrocytes
      administered per week per kilogram of body weight. Percentage of HbS were
      significantly lower in three subjects than in the other eight (6.1 +/- 0.6 vs
      23.0 +/- 2.1; p = 0.0009) as were the reticulocyte percentages (2.9 +/- 0.3 vs
      7.9 +/- 0.7; p = 0.0021). However, there were no significant differences between
      pretransfusion hematocrit (0.278 +/- 0.012 vs 0.281 +/- 0.01; p = 0.90) and units
      of erythrocytes given per week per kilogram (0.0147 +/- 0.0008 vs 0.0156 +/-
      0.0009; p = 0.58). Factors explored to define the reason that HbS synthesis was
      more easily suppressed in some patients than in others included measurements of
      serum chemistry values and erythropoietin, identification of erythrocyte
      alloantibodies, and a survey for Howell-Jolly bodies. No significant differences
      were seen. Although the reasons for the marked variation in transfusion-induced
      depression of HbS synthesis are unclear, this study emphasizes the importance of
      determining the units of packed erythrocytes needed per week per kilogram and
      correlating this value with the pretransfusion HbS percentage. By doing so, one
      can select the minimal amount of blood necessary to achieve the desired HbS
      percentage and thereby decrease the risks of transfusion.

PMID- 8301426
TI  - Epidemiology of Guillain-Barre syndrome in children: relationship of oral polio
      vaccine administration to occurrence.
AB  - Because a cluster of cases of Guillain-Barre syndrome followed a mass vaccination
      program using oral polio vaccine, a retrospective epidemiologic survey was
      carried out in southern California to examine the relationship between oral polio
      vaccine and Guillain-Barre syndrome. We also examined the yearly pattern of
      Guillain-Barre syndrome and compared rates of illness in different ethnic
      populations. The mean annual incidence of Guillain-Barre syndrome was 0.60 (95%
      confidence intervals 0.48 to 0.73) per 100,000 children under 15 years of age.
      There was no difference in incidence between boys and girls or between ethnic
      populations. The incidence was significantly higher in 2-year-old children than
      in any other age group (p < 0.05). The onset of Guillain-Barre syndrome was
      preceded by an infection in 71 (76%) of 93 children. In five children (5%) a
      vaccination was given within 8 weeks before illness onset. Only two children
      received the oral polio vaccine; the duration from vaccine administration to the
      onset of Guillain-Barre syndrome was 41 and 52 days, whereas the mean incubation
      time associated with infectious illnesses was 10.3 days. Strong evidence against
      a causal relationship between oral polio vaccine administration and Guillain
      Barre syndrome is provided by the failure to find a correlation between the usual
      age of immunization with oral polio vaccine and the incidence of Guillain-Barre
      syndrome by age and the failure to find any children with onset of Guillain-Barre
      syndrome within 1 month of immunization with oral polio vaccine.

PMID- 8301427
TI  - Endomyocardial biopsies for early detection of mitochondrial disorders in
      hypertrophic cardiomyopathies.
AB  - Considering the high proportion of unexplained hypertrophic cardiomyopathies on
      the one hand and the occurrence of cardiomyopathies in several mitochondrial
      disorders on the other, we hypothesized that isolated hypertrophic
      cardiomyopathies in infancy could occasionally be the result of defects of
      oxidative phosphorylation. By means of a scaled-down technique, we were able to
      investigate oxidative phosphorylation on minute amounts of endomyocardial tissue
      (1 mg) in three patients with concentric hypertrophic cardiomyopathy (shortening
      fraction in diameter, 18% to 27%; normal mean +/- 1 SD, 33 +/- 3%) and in control
      subjects. Although the absolute respiratory chain enzyme activities in the
      endomyocardial biopsy specimens of the patients were within the low normal range,
      the determination of the activity ratios allowed us to ascribe hypertrophic
      cardiomyopathies to respiratory chain enzyme abnormalities in all three cases
      (complex I, two cases; multiple enzyme deficiency, one case). The respiratory
      chain enzyme activity ratios, which are normally constant irrespective of the
      tissue tested, were markedly abnormal in all three patients (cytochrome c
      oxidase/reduced nicotinamide-adenine dinucleotide cytochrome c reductase, 4.6 to
      10.4; normal mean +/- 1 SD, 2.9 +/- 0.5). We conclude that mitochondrial
      disorders should be regarded as potential causes of hypertrophic cardiomyopathy
      in early infancy. Because cardiac catheterization is routinely performed for
      hemodynamic investigation of cardiomyopathies, we suggest that endomyocardial
      biopsies be considered as a tool for early detection of mitochondrial
      cardiomyopathies, especially in hypertrophic forms of the disease.

PMID- 8301428
TI  - Effect of ascorbate or N-acetylcysteine treatment in a patient with hereditary
      glutathione synthetase deficiency.
AB  - A 45-month-old girl with 5-oxoprolinuria (pyroglutamic aciduria), hemolysis, and
      marked glutathione depletion caused by deficiency of glutathione synthetase was
      followed before and during treatment with ascorbate or N-acetylcysteine. High
      doses of ascorbate (0.7 mmol/kg per day) or N-acetylcysteine (6 mmol/kg per day)
      were given for 1 to 2 weeks without any obvious deleterious side effects.
      Ascorbate markedly increased lymphocyte (4-fold) and plasma (8-fold) levels of
      glutathione. N-Acetylcysteine also increased lymphocyte (3.5-fold) and plasma (6
      fold) levels of glutathione. After these treatments were discontinued, lymphocyte
      and plasma glutathione levels decreased rapidly to pretreatment levels. Ascorbate
      treatment was extended for 1 year, and lymphocyte (4-fold) and plasma (2- to 5
      fold) glutathione levels remained elevated above baseline. In parallel, the
      hematocrit increased from 25.4% to 32.6%, and the reticulocyte count decreased
      from 11% to 4%. The results demonstrate that ascorbate and N-acetylcysteine can
      decrease erythrocyte turnover in patients with hereditary glutathione deficiency
      by increasing glutathione levels.

PMID- 8301429
TI  - Delta 4-3-oxosteroid 5 beta-reductase deficiency causing neonatal liver failure
      and hemochromatosis.
AB  - Neonatal liver failure was evaluated in two infants. Neither infant had evidence
      of congenital infection, galactosemia, alpha 1-antitrypsin deficiency,
      tyrosinemia, Zellweger syndrome, or hemophagocytic lymphohistiocytosis. Abnormal
      levels of iron were detected in the minor salivary glands of the first infant and
      in the explanted liver of the second. Analyses of urinary bile salts by fast-atom
      bombardment ionization mass spectrometry and gas chromatography-mass spectrometry
      revealed a paucity of primary bile acids and a predominance of 7 alpha-hydroxy-3
      oxo-4-cholenoic and 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acids. These
      findings are consistent with delta 4-3-oxosteroid 5 beta-reductase deficiency, a
      primary genetic defect in bile acid synthesis. Postmortem evaluation of the first
      infant revealed significant iron deposition in the liver, pancreas, thyroid,
      adrenal glands, myocardium, stomach, and submucosal glands of the respiratory
      tract. In both infants examination of the liver revealed extensive loss of
      hepatic parenchyma. These cases expand the clinical spectrum of bile acid
      metabolism defects to include neonatal liver failure with associated
      hemochromatosis.

PMID- 8301430
TI  - Pancreatitis in patients with organic acidemias.
AB  - STUDY OBJECTIVE: The discovery of pancreatitis in two children with methylmalonic
      acidemia led us to review the experience with pancreatitis in a large number of
      patients with organic acidemias to determine whether pancreatitis is an important
      complication of these disorders. DESIGN: Case series. SETTING: Pediatric
      metabolism services at five tertiary care centers. PATIENTS: Records of all
      patients with organic acidemias followed at the five institutions during the past
      10 years were reviewed. Pancreatitis was recognized by symptoms and laboratory
      findings and confirmed by imaging studies, surgery, or autopsy. At three
      institutions all cases of pancreatitis in children younger than 10 years were
      reviewed. MEASUREMENTS AND RESULTS: Nine children with pancreatitis (seven with
      acute and two with chronic cases) were identified among 108 children with
      branched-chain organic acidemias. They ranged in age from 13 months to 9 years.
      Five had methylmalonic acidemia, three had isovaleric acidemia, and one had maple
      syrup urine disease. There were three deaths; acute hemorrhagic pancreatitis
      occurred in two children, and chronic pancreatitis was found at autopsy in a
      third. All three patients with isovaleric acidemia and pancreatitis were
      identified after the occurrence of pancreatitis. The survey of pancreatitis at
      three institutions found 57 other patients (none with an inborn error) in
      addition to three patients with inborn errors included in this study.
      CONCLUSIONS: Acute or chronic pancreatitis may complicate branched-chain organic
      acidemias and must be considered in the assessment of patients with these
      disorders who have acute clinical deterioration and vomiting, abdominal pain,
      encephalopathy or shock, or milder symptoms. Conversely, an inborn error of
      organic acid metabolism should be considered in children with pancreatitis of
      unknown origin.

PMID- 8301431
TI  - Improvement of nutritional status and lung function after long-term nocturnal
      gastrostomy feedings in cystic fibrosis.
AB  - We investigated weight gain and clinical course of 14 patients with cystic
      fibrosis (CF), aged 7 to 23 years, who received long-term nocturnal supplemental
      feedings by means of percutaneous endoscopic gastrostomies (PEGs). The patients
      (nine female, five male) were moderately malnourished; the weight-for-height
      value was 77.8% (SD 6.4%) of the predicted value. Lung function tests revealed
      severe airway obstruction; mean vital capacity was 46.1% (SD 14.4%), and mean
      forced expiratory volume in 1 second (FEV1) was 30.8% (SD 12.3%) of predicted
      value. A nonelemental formula providing 35% of total energy from fat was used for
      nocturnal feedings. The patients received 800 to 1500 kcal per night by slow
      intragastric infusions. Enteric-coated pancreatic microsphere preparations were
      taken orally just before bedtime. After 1 year of supplemental feedings, body
      weight had increased by 6.0 kg (SD 3.6 kg) and weight-for-height value by 9.0%
      (SD 6.1%) of predicted compared with baseline values. Lung function also improved
      significantly: vital capacity increased by 8.2% (SD6.3%) and FEV1 by 3.9% (SD
      4.2%) of predicted values (p < 0.01). The total duration of nocturnal feedings
      was 364 months, or 26 months per patient. Nine of the fourteen patients continue
      to use the PEG, three patients had the PEG tube removed, and two patients have
      died 21 and 23 months after PEG insertion. We conclude that nocturnal PEG
      feedings of malnourished patients with CF improve nutritional status and lung
      function without major side effects.

PMID- 8301432
TI  - Comparison of manual and mechanical chest percussion in hospitalized patients
      with cystic fibrosis.
AB  - We compared the efficacy of manual and mechanical chest percussion during
      hospitalization for acute exacerbations of cystic fibrosis by evaluating changes
      in spirometry values. Fifty-one participants were randomly assigned to receive
      manual or mechanical chest percussion three times a day. Twenty-two participated
      during one subsequent admission and were assigned to the opposite form of chest
      percussion. The two groups were equal in severity of illness (mean National
      Institutes of Health score (+/- SEM): manual = 66.7 +/- 2.2; mechanical = 35.8 +/
      2.2; p = not significant). Mean improvement in forced expiratory volume at 1
      second, forced vital capacity, and forced expiratory flow between 25% and 75% of
      forced vital capacity (+/- SEM) for manual percussion was 32.6% +/- 7%, 27.2% +/-
      5%, and 38.1% +/- 10%, and for mechanical percussion was 28.5% +/- 4%, 28.7% +/-
      4%, and 25.1% +/- 8%, respectively; p = not significant. Our participants did not
      prefer mechanical chest percussion. Although equal efficacy of outpatient therapy
      remains to be proved, this study suggests that patients can be encouraged to use
      the form of chest percussion that they prefer.

PMID- 8301433
TI  - Clinical evaluation of the macroduct sweat collection system and conductivity
      analyzer in the diagnosis of cystic fibrosis.
AB  - The purposes of this study were to compare sweat tests used in diagnosing cystic
      fibrosis (CF), as performed with the Macroduct collection system, with those
      utilizing the more laborious quantitative pilocarpine iontophoresis test (QPIT),
      and to ascertain the efficacy of the Sweat-Chek conductivity analyzer in
      eliminating some possibly unnecessary chloride analyses. A Macroduct sweat test
      was performed on one arm and a QPIT on the other on 1090 patients, 93 of whom had
      CF. Of these, 514 patients (43 with CF) also had a conductivity determination on
      the Macroduct sweat sample. All subjects were referred to the laboratory of one
      of us (K.B.H.) for sweat testing. Of the QPIT samples, 0.7% were inadequate, as
      were 6.1% of those from the Macroduct system. When sodium and chloride
      concentrations from the two tests were compared, the standard errors of the
      estimate were 3.90 and 3.85, respectively. Agreement within 8 mEq/L could then be
      expected with 95% confidence limits. With use of the Sweat-Chek analyzer, no
      patient with CF was found to have a conductivity of less than 90 mmol/L, whereas
      430 (91%) of the non-CF subjects had a conductivity of less than 50 mmol/L. None
      of those 430 subjects had a sweat chloride value > 32 mmol/L. We conclude that
      the Macroduct collection system provides results equally as satisfactory as those
      provided by the QPIT and that the Sweat-Chek analyzer frequently eliminates the
      necessity of measuring chloride concentrations.

PMID- 8301434
TI  - Experience with pediatric lung transplantation.
AB  - Heart-lung transplantation and lung transplantation have become accepted
      techniques in adult patients with end-stage cardiopulmonary disease. We report
      here our experience between July 1985 and March 1993 with 34 children (< 20
      years) who underwent heart-lung (n = 18) or lung transplantation (n = 17).
      Indications for transplantation included cystic fibrosis (n = 9), congenital
      heart disease with Eisenmenger complex (n = 9), primary pulmonary hypertension (n
      = 8), pulmonary arteriovenous malformations (n = 2), desquamative interstitial
      pneumonia (n = 2), Proteus syndrome with multicystic pulmonary disease (n = 1),
      graft-versus-host disease (n = 1), rheumatoid lung disease (n = 1), and
      bronchiolitis obliterans and emphysema (n = 1). Twenty-six patients (76%) have
      survived from 1 to 88 months after transplantation; most patients have returned
      to an active lifestyle. Of the eight deaths, four were due to infections, two to
      multiorgan failure, 1 to posttransplant lymphoproliferative disease, and one to
      donor organ failure. Four of the patients who died had cystic fibrosis. Despite
      considerable morbidity related to infection, rejection, and function of the heart
      lung and lung allograft in some patients, our results with this potentially
      lifesaving procedure in the pediatric population have been encouraging.

PMID- 8301435
TI  - Experience with pediatric lung transplantation.

PMID- 8301436
TI  - Varicella in children with perinatally acquired human immunodeficiency virus
      infection.
AB  - Thirteen children with human immunodeficiency virus infection acquired
      perinatally and with varicella were identified. Clinical and epidemiologic
      information, including the use of varicella immune globulin and acyclovir, was
      obtained and testing for antibodies to varicella-zoster virus was done. The 13
      children infected with human immunodeficiency virus had an uncomplicated clinical
      course, and many had a significant antibody response to varicella-zoster virus.

PMID- 8301437
TI  - Disseminated measles infection after vaccination in a child with a congenital
      immunodeficiency.
AB  - An infant boy with a congenital immunodeficiency had fatal disseminated measles
      after administration of a live attenuated measles vaccine. This rare complication
      was confirmed with molecular virologic techniques. Although efforts to expand
      availability of vaccinations are critically important, caution is warranted in
      children with potentially severe immunologic dysfunction.

PMID- 8301438
TI  - Free triiodothyronine toxicosis in two adolescents.
AB  - Two male adolescents had subtle symptoms and signs of thyrotoxicosis but normal
      levels of total and free thyroxine and total triiodothyronine. Serum
      concentrations of thyrotropin were undetectable in basal specimens and after
      administration of thyrotropin-releasing hormone; only free triiodothyronine
      values were elevated. An increase in serum levels of free triiodothyronine may be
      the earliest secretory abnormality of an overactive thyroid gland.

PMID- 8301439
TI  - Renal rupture after the Crede maneuver.
AB  - We report a case of renal rupture with development of a large perinephric urinoma
      and deterioration of renal function after the Crede maneuver in a girl with
      neurogenic bladder and detrusor sphincter dyssynergia without vesicoureteral
      reflux. After percutaneous drainage of the urinoma, management was changed to
      clean intermittent catheterization, and renal function returned to normal. We
      recommend that the Crede maneuver not be used in children with neurogenic bladder
      and nondenervated urethral sphincter.

PMID- 8301440
TI  - Metabolic response of preterm infants to variable degrees of respiratory illness.
AB  - In older children and adults, physiologic instability associated with severe
      illness causes increased cellular oxygen consumption (VO2), increased serum
      lactate and cortisol levels, and more negative nitrogen balance. To determine the
      metabolic response of preterm infants to severity of respiratory illness, we
      analyzed VO2, nitrogen balance, urinary 3-methyl-histidine and norepinephrine
      concentrations, and serum levels of lactate and cortisol as a function of
      ventilatory index (VI). Twelve 2-day-old premature infants who were appropriate
      in size for gestational age (mean +/- SEM birth weight: 1460 +/- 251 gm) and who
      required mechanical ventilation for respiratory distress syndrome had VO2 and
      carbon dioxide production measured by indirect calorimetry and blood and urine
      samples obtained concurrently. All infants received amino acids, 1.0 gm/kg per
      day, and a mean energy intake of 27 +/- 3 kcal/kg per day, provided as a
      parenteral dextrose solution. The resting energy expenditure exceeded energy
      intake in all infants. The VO2 value ranged from 5.5 to 9.2 ml/kg per minute and
      was directly correlated with VI (r = 0.79; p = 0.002). Nitrogen balance ranged
      from -160 to 53 mg/kg per day (mean: -33 +/- 21 mg/kg per day) but was not
      dependent on VI (r = 0.04) or VO2 (r = 0.01). The serum lactate level correlated
      directly with VI (r = 0.82; p = 0.002) and VO2 (r = 0.60; p = 0.05), but cortisol
      and urinary norepinephrine levels did not. We conclude that preterm infants with
      respiratory distress syndrome have increased VO2 rates and serum lactate
      concentrations directly related to the degree of respiratory illness. They are
      generally in a state of mildly negative nitrogen balance, the degree of which is
      not related to severity of illness. Although these infants may require increased
      energy delivery during illness, they do not appear to require excessive amounts
      of amino acids.

PMID- 8301441
TI  - Pathophysiology of congenital diaphragmatic hernia. V. Effect of exogenous
      surfactant therapy on gas exchange and lung mechanics in the lamb congenital
      diaphragmatic hernia model.
AB  - The aim of this study was to assess the impact of surfactant deficiency on the
      pathophysiology of congenital diaphragmatic hernia (CDH). Pregnant ewes were
      operated on at 80 days of gestation for creation of a diaphragmatic hernia in the
      lambs. Twenty-one lambs survived to be delivered by cesarean section and were
      studied. Compliance was improved when surface tension effects were removed by
      saline solution in lungs of both control animals and lambs with CDH; however, the
      lungs of the lambs with CDH still had significantly impaired compliance. In a
      second series of experiments, two groups were studied: a surfactant-treated and a
      control, nontreated group. Surfactant was given prophylactically into the liquid
      filled lungs before the first breath. All lambs were paralyzed and sedated and
      their lungs mechanically ventilated with 100% oxygen for 30 minutes; gas exchange
      was then assessed, pressure-volume data were obtained, and compliance was
      calculated. Surfactant significantly improved gas exchange; arterial oxygen
      pressure increased from 39 +/- 11.4 to 316 +/- 53.6 mm Hg, arterial carbon
      dioxide pressure decreased from 148 to 63 mm Hg, and pH increased from 6.87 to
      7.16 (p < 0.001). Lung volume at 25 cm H2O, functional residual capacity, and
      compliance were all increased (p < 0.02). Thus, in the CDH lamb model, pulmonary
      mechanics are impaired by both parenchymal and surfactant abnormalities. Both
      lung mechanics and gas exchange are markedly improved by exogenous surfactant
      therapy.

PMID- 8301442
TI  - Comparison of the effect of three doses of a synthetic surfactant on the alveolar
      arterial oxygen gradient in infants weighing > or = 1250 grams with respiratory
      distress syndrome. American Exosurf Neonatal Study Group II.
AB  - The effect of a 50% increment or decrement in the recommended 5 ml/kg dose of a
      commercially available surfactant (Exosurf Neonatal) on the alveolar-arterial
      oxygen gradient was investigated in a multicenter, double-blind, placebo
      controlled rescue trial conducted at 15 hospitals in the United States. Two doses
      of three different volumes (2.5, 5.0, and 7.5 ml/kg) were compared with two 5.0
      ml/kg doses of air in 281 infants weighing > or = 1250 gm who had respiratory
      distress syndrome requiring mechanical ventilation and an arterial/alveolar
      oxygen ratio < 0.22. The first dose was given between 2 and 24 hours of age, and
      the second dose was given 12 hours later to all infants who still required
      mechanical ventilation. Infants were stratified at entry by gender and the
      magnitude of the arterial/alveolar oxygen ratio. The air placebo arm of the study
      was terminated early when reductions in mortality rates were proved in another
      rescue trial of this surfactant in infants with the same birth weights. For the
      first 48 hours, administration of a 2.5 ml/kg dose of surfactant provided less
      improvement in the alveolar-arterial oxygen gradient than doses of 5.0 and 7.5
      ml/kg, which were equivalent. Similar results were observed in mean airway
      pressure (p < 0.05). There were no significant differences among the three dosage
      groups in mortality rate, air leak, bronchopulmonary dysplasia, and other
      complications of prematurity. There were no pulmonary hemorrhages in any group.
      Reflux of surfactant occurred more frequently in the 5.0 and 7.5 ml/kg groups.
      These results indicate that more sustained improvements in oxygenation are
      provided, with equal safety, by the standard two 5.0 ml/kg rescue doses of this
      surfactant than by the 2.5 ml/kg dose. No further benefit is gained from two
      larger doses given 12 hours apart.

PMID- 8301443
TI  - Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation:
      dose response.
AB  - To determine the role of inhaled nitric oxide (NO) in a population of critically
      ill hypoxic near-term infants and to determine the dose response to inhaled NO,
      we examined a consecutive group of 23 infants referred for neonatal
      extracorporeal membrane oxygenation (ECMO) who had an oxygen index of 20 or
      greater after treatment with bovine surfactant. Inhaled NO was administered in
      concentrations from 5 to 80 ppm in random order to 23 infants. Overall, 13
      infants had a significant response (an improvement in arterial oxygen pressure >
      10 mm Hg or arterial oxygen saturation > 10%) to the first administration of
      inhaled NO, and one infant had a late response. There was no significant
      difference in the response to inhaled NO as measured by changes in arterial
      oxygen pressure or in the alveolar-arterial difference in partial pressure of
      oxygen, for any of the doses from 5 to 80 ppm. Thirteen infants had
      echocardiographic evidence of persisted pulmonary hypertension; 11 of these
      infants responded, compared with 3 responders among the 10 infants without
      persistent pulmonary hypertension of the newborn (p < 0.01). Overall, 11 infants
      required ECMO; there were two deaths in this group. Seven infants had congenital
      diaphragmatic hernia; five of those had a response to NO inhalation and four
      required ECMO. Our study demonstrates that there is no significant difference in
      response between low and high doses of inhaled NO and that this treatment may
      prevent the need for ECMO in some infants referred for this therapy, especially
      in infants with pulmonary hypertension. Prospective, controlled, randomized, and
      blinded trials of low doses of inhaled NO are needed to determine the clinical
      role of this potentially useful therapy.

PMID- 8301444
TI  - Phototherapy-associated changes in mesenteric blood flow response to feeding in
      term neonates.
AB  - Doppler blood flow velocity of the superior mesenteric artery was measured
      preprandially and postprandially in 12 term neonates during phototherapy and 4
      hours after discontinuation of this therapy. The postprandial increase in blood
      flow velocity was significantly less during than after phototherapy. We suggest
      that the phototherapy-induced peripheral vasodilation may be responsible for
      diverting blood from the intestines and limiting the normal neonatal postprandial
      response.

PMID- 8301446
TI  - Ganciclovir therapy for symptomatic congenital cytomegalovirus infection in
      infants: a two-regimen experience.
AB  - The efficacy of two regimens of ganciclovir therapy was evaluated in 12 infants
      with symptomatic congenital cytomegalovirus (CMV) infection. Virologic
      investigations included culture from urine, saliva, and cerebrospinal fluid,
      detection of CMV DNA by polymerase chain reaction, and detection of CMV class
      specific antibodies (IgG, IgA, IgM) by enzyme immunoassays. Six infants were
      given ganciclovir, 5 mg/kg twice daily for 2 weeks (group 1); the other six
      infants were given 7.5 mg/kg twice daily for 2 weeks and 10 mg/kg three times
      weekly for 3 months (group 2). In group 1 the CMV cultures of specimens from
      three infants became sterile; two of these infants also had negative results on
      CMV DNA studies; results of culture and CMV DNA study were still positive after
      ganciclovir therapy in the remaining three infants. Subsequently, normal outcome
      was observed in only two patients. In group 2, all infants had negative CMV
      culture and CMV DNA results; clinical improvement was evident in five infants,
      one of whom had later development of mild psychomotor retardation. In another
      infant, severe psychomotor retardation and hearing loss developed after transient
      improvement developed. These preliminary data indicate that a ganciclovir regimen
      including a higher dose and more prolonged therapy might be more effective in
      infants with symptomatic congenital CMV infection.

PMID- 8301445
TI  - Efficacy of oral meso-2,3-dimercaptosuccinic acid therapy for low-level childhood
      plumbism.
AB  - OBJECTIVE: To compare the response to oral meso-2,3-dimercaptosuccinic acid
      (DMSA) treatment in children with an initial blood lead (BPb) concentration less
      than versus more than 2.17 mumol/L (45 micrograms/dl). DESIGN: Retrospective
      cohort study. SETTING: Regional referral lead treatment program in an urban
      children's hospital. PATIENTS: Thirty consecutive children, median age 34 months
      (range, 5 to 161 months), with an initial BPb concentration 0.97 to 2.90 mumol/L
      (20 to 60 micrograms/dl) selected for DMSA use. Reasons for DMSA use included BPb
      concentration > 2.17 mumol/L (11 children), complications with penicillamine
      therapy (11), chronic renal failure (1), and compassionate use (7). All patients
      received required environmental hazard reductions before drug administration.
      RESULTS: Group 1 (n = 23) had a mean BPb concentration of 1.50 mumol/L (31
      micrograms/dl), and group 2 (n = 7) had a mean BPb concentration of 2.41 (51
      micrograms/dl). Sixteen patients (70%) in group 1 and five patients (71%) in
      group 2 had had previous chelation therapy (p value not significant). No
      significant difference was found in the mean percentage of the reduction of BPb
      concentration during treatment of group 1 (60%) versus group 2 (58%). The mean
      BPb concentration in group 1 rebounded to 70% of pretreatment values by mean day
      41; the BPb concentration in group 2 rebounded to 69% by day 37 (p value not
      significant). Prior chelation therapy did not result in a significant difference
      in either the percentage reduction of BPb concentration or the percentage of
      rebound BPb. CONCLUSION: DMSA is equally effective in acutely lowering BPb
      concentration in children with BPb concentrations less than and greater than 2.17
      mumol/L.

PMID- 8301447
TI  - Immunogenicity and safety of Haemophilus influenzae type b-tetanus protein
      conjugate vaccine alone or mixed with diphtheria-tetanus-pertussis vaccine in
      infants.
AB  - Haemophilus capsular polysaccharide-tetanus toxoid conjugate (PRP-T) and
      diphtheria-tetanus-pertussis (DTP) vaccines were administered in a single syringe
      (group 1) or separate syringes (group 2) to 284 infants at 2, 4, and 6 months of
      age. Group 1 infants had a slightly greater incidence of local reactions.
      Systemic reactions were similar. The geometric mean titers of polyribosylribitol
      phosphate (PRP) serum antibody concentrations after the third dose of PRP-T
      vaccine were 4.8 and 4.3 micrograms/ml for groups 1 and 2, respectively. Antibody
      responses to DTP antigens were also similar. The immunogenicity and safety of the
      PRP-T and DTP vaccines are equivalent when the vaccines are administered in
      separate syringes or the same syringe to infants.

PMID- 8301448
TI  - Vitamin A and bronchopulmonary dysplasia.

PMID- 8301449
TI  - Bone marrow transplantation for sickle cell anemia.

PMID- 8301450
TI  - Treatment of infection-associated hemophagocytic syndrome with immune globulin.

PMID- 8301451
TI  - Optimal dose of omeprazole in infants and children.

PMID- 8301452
TI  - Hepatic toxic effects associated with valproate therapy.

PMID- 8301453
TI  - Performance of plasma-perfused, microencapsulated hepatocytes: prospects for
      extracorporeal liver support.
AB  - The growing success of liver transplantation and the shortage of donor livers has
      turned attention to the possibility of utilizing hepatocytes within artificial
      liver support systems to allow time for donor livers to become available and to
      improve the condition of patients with hepatic failure. This study evaluated
      encapsulated hepatocytes, a technology which might allow the possibility of using
      xenogenic or human hepatoma cells. Rabbit hepatocytes were encapsulated using the
      ionic polysaccharides carboxymethylcellulose, chondroitin sulfate A, chitosan,
      and polygalacturonic acid. Encapsulated cells were maintained in perfusion
      culture for at least 6 days in heparinized, normal human plasma or in a defined
      culture medium. Parallel cultures of plated hepatocytes were also conducted. The
      metabolic capability of the cells was evaluated by following the rates of urea,
      albumin, and transferrin synthesis and the transformation rate of the drug
      antipyrine. Protein synthesis and ureogenesis in plasma were depressed from the
      levels expressed in defined culture medium. Drug detoxification as measured by
      antipyrine metabolism appeared to be enhanced in plasma. We conclude that
      encapsulated rabbit hepatocytes retain significant levels of function for at
      least 6 days of perfusion with human plasma, suggesting the feasibility of this
      technology as a potential method of short-term liver support.

PMID- 8301454
TI  - The effect of prostaglandin E1 analog misoprostol on chronic cyclosporin
      nephrotoxicity.
AB  - Cyclosporin A has markedly improved graft survival in transplant patients but its
      side effects, such as renal toxicity and hypertension, pose management problems
      in transplant recipients. This toxicity has been attributed to prostaglandin
      inhibition. Concurrent administration of misoprostol (a prostaglandin E1 analog)
      prevents chronic cyclosporin A-induced nephrotoxicity but not hypertension in
      rats.

PMID- 8301455
TI  - Experimental fetal tracheal ligation prevents the pulmonary hypoplasia associated
      with fetal nephrectomy: possible application for congenital diaphragmatic hernia.
AB  - Pulmonary hypoplasia has a definite clinical impact in a variety of congenital
      diseases such as renal dysplasia and congenital diaphragmatic hernia. These
      diseases have in common inadequate growth and development of fetal lungs.
      Previous reports have demonstrated increased lung growth with in utero tracheal
      ligation. The purpose of this study was to determine if lung growth can be
      accelerated in the setting of experimental pulmonary hypoplasia. Ninety-five-day
      gestation fetal sheep were divided into four experimental groups: nephrectomy,
      nephrectomy with tracheal ligation, tracheal ligation alone, and sham-operated
      control animals. Animals were delivered near term and their lungs inflation fixed
      at 25 cm H2O. Total alveolar number (Alv#), total alveolar surface area (AlvSA),
      and lung volume to body weight ratios (LV:BW) were determined for apical and
      basilar segments of each animal and then averaged. Total lung DNA and protein
      content were also analyzed. The nephrectomy group had smaller lungs than control
      animals with decreased Alv#, AlvSA, and LV:BW. In contrast, nephrectomy with
      tracheal ligation produced large lungs which had increased Alv#, AlvSA, and LV:BW
      when compared with both the nephrectomy and the control group (P < .01). Total
      lung DNA and protein concentrations were both markedly elevated in the tracheally
      obstructed groups. However, the DNA/protein ratios remained constant in all four
      groups, suggesting that lung growth had occurred through cell multiplication.
      Photomicrographs of the lung demonstrated a histologically immature appearance in
      the nephrectomy group and a histologically mature appearance in the tracheally
      obstructed groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301456
TI  - Efficacy of passive immunotherapy in experimental postsplenectomy sepsis due to
      Haemophilus influenzae type B.
AB  - In an effort to develop a more effective therapy for postsplenectomy sepsis,
      ceftriaxone and human intravenous immunoglobulin (IVIG), alone and in
      combination, were evaluated for their efficacy against experimental Haemophilus
      influenzae type B (Hib) bacteremia in splenectomized and sham-operated infant
      rats. Five-day-old animals had either a splenectomy or sham operation. At 12 days
      of age, they were challenged intraperitoneally with Hib. Fifteen hours later
      blood specimens were obtained for quantitative bacterial cultures, and
      immediately thereafter therapy was started with ceftriaxone, IVIG, combination of
      ceftriaxone and IVIG, or albumin (control). Quantitative blood cultures were
      repeated 24 and 48 hours after the treatment. Prior to the treatments,
      splenectomized animals had significantly higher bacterial counts in blood when
      compared with sham-operated animals (P < .001). Splenectomized animals receiving
      IVIG, ceftriaxone, or the combination of IVIG and ceftriaxone had significantly
      increased bacterial clearance from blood when compared with the controls (P <
      .01). In addition, animals treated with ceftriaxone or the combination of IVIG
      and ceftriaxone had significantly increased bacterial clearance compared with the
      IVIG alone treatment group (P < .01). Overall, the mortality was significantly
      higher in splenectomized animals compared with the sham-operated animals (P <
      .05). The control animals had significantly higher mortality compared with the
      IVIG, ceftriaxone, and combined ceftriaxone and IVIG treatment groups (P < .05).
      There were no detrimental effects of combining IVIG and ceftriaxone together.

PMID- 8301457
TI  - Fibromatosis in infancy and childhood: the spectrum.
AB  - Fibromatoses form an interesting group of tumors occupying a midposition in the
      spectrum of fibrous tissue neoplasms. Within the fibromatoses subgroups there
      exists a variety of tumors whose clinical behavior spans the range from
      completely benign to locally aggressive. Four case histories are presented to
      illustrate this point. All four patients were initially seen with asymptomatic
      head or neck masses. The first had complete excision with no recurrence to date.
      The second underwent spontaneous regression after confirmation of diagnosis with
      biopsy. The third case had a very locally aggressive disease requiring three
      surgical resections to date, while the last case had one recurrence after the
      initial resection. With certain exceptions, initial wide local excision offers
      the best possible chance for cure.

PMID- 8301458
TI  - Wound healing in the fetal period: the resistance of the scar to rupture.
AB  - Wound healing in the fetal period is fundamentally different from that of the
      adult. In order to better understand this difference, we have studied wound
      healing in three types of wounds which are the most common in surgical practice,
      and have paid special attention to tensile strength in the scar. A sutured wound,
      a nonsutured wound, and an electrocautery burn were performed on a group of 30
      rabbit fetuses with a gestational age of 23 days. Seven days later, the resulting
      scars were examined using histological, mechanical, and biochemical studies. The
      results were compared with those obtained in a group of 30 newborn rabbits and in
      a group of 30 adult rabbits who had had the same type of wounds performed on
      them. The body weight of operated fetuses was smaller than their control
      siblings. The sutured wound in the fetuses showed a more perfect macroscopic
      repair than in older subjects. However, the nonsutured wounds and the burns of
      the fetal group did not close. In the fetuses, the tensile strength of the
      sutured wound was 20% of the tensile strength of healthy skin. A similar
      relationship occurred in the group of adult rabbits. In the sutured wound of the
      fetal group, the synthesis of collagen was significantly less than in the adult
      group. The ratio between hydroxyproline (HYP) concentration in the sutured wound
      and HYP concentration in healthy skin was also significantly less in the fetal
      group than in the adult group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301459
TI  - Persistent pulmonary hypertension in high-risk congenital diaphragmatic hernia
      patients: incidence and vasodilator therapy.
AB  - Survival of congenital diaphragmatic hernia patients depends on the gravity of
      pulmonary hypoplasia and persistent pulmonary hypertension (PPH). Many vasoactive
      drugs have been used in the treatment of PPH, but often they also lower
      peripheral resistance, leading to a significant drop in arterial blood pressure.
      The incidence of PPH in 52 high-risk diaphragmatic hernia patients and the
      results of treatment with tolazoline and prostacyclin were evaluated in a study
      lasting 52 months and involving 52 patients. High-risk patients require
      ventilatory support within 6 hours after birth. Study parameters were alveolar
      arterial oxygenation difference (AaDO2), oxygenation index (OI), and mean
      arterial blood pressure (MABP), measured at set times before and after
      administration of tolazoline or prostacyclin. Twenty-one patients had documented
      episodes of PPH (46%), and 18 of them died. Tolazoline did not lower AaDO2 and OI
      values, but MABP dropped significantly. Prostacyclin caused a significant
      decrease of AaDO2 and OI values without an effect on MABP. We concluded: (1) PPH
      presented in 46% of our patients, associated with a high mortality rate; (2)
      tolazoline is not an effective dilator of the pulmonary vascular bed and lowers
      MABP; and (3) prostacyclin is an effective pulmonary vasodilator as reflected by
      ventilation parameters without systemic side effects; it does not affect overall
      outcome but can used as a "bridge" to extracorporeal membrane oxygenation.

PMID- 8301460
TI  - Postoperative analgesia following thoracotomy in children: interpleural
      catheters.
AB  - The authors retrospectively review their experience in children with the latest
      addition to the postoperative analgesic armamentarium: interpleural analgesia
      (IPA). IPA was used in 14 children following thoracotomy. There were 9 boys and 5
      girls. Patients varied in age from 2 months to 17 years 4 months (mean +/- SEM =
      7.6 +/- 1.6 yr). Catheters were left in place from 10 to 72 hours (mean +/- SEM =
      45.1 +/- 4.6 h). Four patients received intermittent bolus doses and 10 patients
      received a continuous infusion through the interpleural catheters. Adequate
      analgesia, as judged by both subjective responses (decreased irritability or
      complaints of pain) and by objective physiologic responses (decreased heart rate,
      respiratory rate, and systolic blood pressure), was achieved in 13 of 14
      patients. Eight of the 14 children required no additional analgesic agents. One
      child received 2 doses of oral codeine and 4 patients received 2 to 3 doses of
      intravenous narcotic during IPA. IPA was not effective in one patient who
      required 6 doses of intravenous meperidine. Patients more than 10 years of age
      required significantly more (P < 0.05) intravenous narcotic supplementation than
      patients less than 10 years of age (1.60 +/- 0.50 v 0.14 +/- 0.11 mg
      meperidine/kg/d). No complications related to placement or subsequent use of IPA
      were identified in any of the patients. IPA provides effective postoperative
      analgesia following thoracotomy in children.

PMID- 8301461
TI  - Preservation of the umbilical cord at the primary fascial closure in infants with
      gastroschisis.
AB  - Recently, the survival of patients with gastroschisis has been dramatically
      improved and it has reached more than 90%. Over the last 10 years, 20 of 21 cases
      (95%) survived in our hospital. We have been using the primary fascial closure of
      the abdominal wall as a standard operative procedure. The umbilical cord was
      usually excised at the operation in order to secure the suture line and prevent
      wound infection. The survivors sometimes complained of the absence of the
      umbilicus. However, it was somewhat difficult to create a new umbilicus later by
      use of the surrounding skin. In the last five cases, we tried to carry out the
      primary fascial closure with preservation of the umbilical cord. All patients
      could obtain good cosmetic results with near-normal appearance. Omphalitis or
      cellulitis was never observed, but a small umbilical hernia occurred in one case.

PMID- 8301462
TI  - Effect of esophageal ligation on the development of fetal rabbit intestinal
      lactase.
AB  - To investigate the effect of normal fetal swallowing and amniotic fluid ingestion
      on small intestinal disaccharidase development, 13 pregnant New Zealand White
      rabbits underwent operation on day 24 of a normal 31-day gestation. The right
      ovarian fetus in the bicornuate uterus underwent esophageal ligation (EL), while
      the contralateral left fetus underwent cervical exploration only, and served as
      the control (C). Rabbits were sacrificed on gestational day 31, fetal somatic
      measurements obtained, and the midjejunum removed for determination of
      disaccharidase activity and protein content. There was one maternal death, and 9
      of 12 fetal pairs survived the entire study period (75%). Results are reported as
      mean +/- SEM, analyzed by two-tailed Student's t testing with P < .05 being
      considered significant. Fetal weight was decreased in EL (48.6 +/- 2.7 g) versus
      C (51.4 +/- 3.2 g) (P = .06). Small intestinal length decreased in EL (49.2 +/-
      2.0 cm) versus C (54.9 +/- 1.1 cm) (P = .01). Midjejunal protein content (mg/mL
      homogenate) was also significantly decreased in EL (38.4 +/- 3.4) versus C (46.2
      +/- 3.7) (P = .05). Sucrase activity was not detectable in either group. Lactase
      activity in jejunal mucosa was not effected when expressed as units of enzyme per
      milliliter of homogenate (EL = 0.357 +/- 0.03 v C = 0.373 +/- 0.04; P = .70) and
      units enzyme per gram of protein (EL = 38.8 +/- 4.2 v C = 34.2 +/- 4.6; P = .44).
      We have confirmed previous studies demonstrating decreases in somatic growth,
      small intestinal length, and mucosal nutrient transport in rabbit fetuses
      following esophageal ligation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301463
TI  - An analysis of feeding regimens after pyloromyotomy for hypertrophic pyloric
      stenosis.
AB  - We retrospectively reviewed 223 infants who underwent pyloromyotomy for
      hypertrophic pyloric stenosis (HPS) at our institution from January 1984 to May
      1990. Each patient's postoperative feeding regimen was determined by the
      attending surgeon. The four distinct regimens used were as follows: A (n = 66):
      NPO overnight (> 10 h) with cautious feeding advancement every 4 hours x 2, then
      every 2 hours x 2, then every 1 1/2 hours x 8, then ad lib; B (n = 46): NPO until
      6 to 8 hours postoperatively with the same cautious feeding advancement as in A;
      C (n = 42): NPO until 6 hours postoperatively with accelerated feeding
      advancement every 2 hours x 8, then ad lib; D (n = 69): NPO until 6 hours
      postoperatively with accelerated feeding advancement every 1 hour x 12, then ad
      lib. There were no significant differences in age at diagnosis or degree of
      dehydration among groups. From group A to group D, there was a progressive
      increase in amount and incidence of postoperative vomiting, both after the first
      three feedings and in the total postoperative period. However, patients in groups
      C and D had a shorter postoperative hospital stay and lower charges than did
      patients in groups A and B. Following discharge, no patient was readmitted for
      vomiting or dehydration. We conclude that feedings started 6 hours after
      pyloromyotomy for HPS with accelerated feeding advancement every 2 hours
      increases the incidence and frequency of postoperative vomiting, but not
      unacceptably, and results in a significantly shorter postoperative stay.

PMID- 8301464
TI  - Duodenal manometry in postobstructive enteropathy in infants with a transient
      enterostomy.
AB  - Intestinal motility was studied in 11 children with a transient enterostomy
      secondary to a neonatal organic small intestine obstruction (5 total colon
      Hirschsprung's disease, 2 necrotizing enterocolitis, 1 intussusception, 3 ileal
      atresia). Eight children presented with a postobstructive enteropathy (severe
      grade I [5], moderate grade II [3]) and three were considered as controls (grade
      III). They were assigned to one of the three groups on the basis of the duration
      of parenteral nutrition and constant rate enteral nutrition needed and the oral
      feeding tolerance. Barium small intestine transit showed no persistent partial
      obstruction or peritoneal adhesions. The abnormal inert marker transit times were
      statistically correlated with the clinical groups as well as duodenal manometric
      abnormalities. Manometric recordings were characterised by the absence (grade I)
      or abnormal phase III (grade II) of the migrating motor complex and decreased
      motility index (grades I and II). This study confirms that this enteropathy is
      due to a chronic alteration in motility induced by prenatal or postnatal
      obstructions.

PMID- 8301465
TI  - Laparoscopic Meckel's diverticulectomy in infants: report of three cases.
AB  - Three infants younger than 2 years presented with episodic bloody-to-tarry stool
      of moderate amount. Two of them were diagnosed to have Meckel's diverticulum
      because of a positive 99mTc pertechnetate scan. Although the third infant had two
      negative radionuclide scans within 3 months, Meckel's diverticulum was still
      suspected by exclusion studies. All three infants underwent laparoscopic surgery.
      At laparoscopy, a Meckel's diverticulum was identified in all. Besides, an
      ileoileo intussusception just proximal to the diverticulum was also found in one
      patient. Reduction of the intussusception and diverticulectomy were performed
      successfully by laparoscopic procedure. Compared with conventional laparotomy,
      this procedure has the advantages of direct preoperative visual confirmation of
      the diagnosis, less traumatic access, much shorter recovery period and perhaps
      fewer intraoperative and postoperative complications. And thus, laparoscopic
      surgery has the potential of becoming regular treatment for symptomatic Meckel's
      diverticulum of infants.

PMID- 8301466
TI  - Complications of typhoid fever requiring laparotomy during childhood.
AB  - All the complications requiring laparotomy among 680 children who were diagnosed
      as having typhoid fever between 1981 and 1990, at Hacettepe University Children's
      Hospital, were retrospectively analyzed. Four patients developed intestinal
      perforation, two gastrointestinal bleeding, and two splenic abscess, with
      frequencies of 0.58%, 0.29%, and 0.29%, respectively. The overall frequency was
      1.17%. While the risk was 1.58% among males, it was 0.42% among females with no
      statistically significant difference (P > .05). The risk was higher among
      patients above 6 years of age (P < .05). While perforation and hemorrhagic
      complications developed within 10 days of initial symptoms and splenic abscess
      required 10 and 30 days for development, there were no clinical signs and
      laboratory findings predicting the occurrence of complications in the course of
      typhoid fever. Two patients, one with intestinal perforation and the other with
      gastrointestinal hemorrhage, died within 2 days following the septic
      postoperative courses. On the other hand, 12 patients, among those without
      complications requiring laparotomy, died of unremitting septic course of the
      disease. The mortality rate rose from 1.78% to 25% when complications occurred.
      The findings in this series demonstrate that typhoid fever presents a challenge
      to the pediatric surgeons not only because of the complications requiring
      laparotomy with high mortality rates, but also the absence of criteria predicting
      the occurrence of complications in the course of typhoid fever.

PMID- 8301467
TI  - Reappraisal of Ekehorn's rectopexy in the management of rectal prolapse in
      children.
AB  - An old and simple operative technique for the treatment of rectal prolapse in
      children, first described by Ekehorn in 1909, has been reviewed. The technique
      consists of the insertion of a mattress suture (nonabsorbable and multifilament
      material) in the rectal ampulla through the lowermost part of the sacrum: the
      strands of the mattress suture are tied firmly over a piece of dry gauze at the
      level of the sacrococcygeal junction. By leaving the suture in place for 10 days,
      the local inflammation and infection causes firm adhesions between the rectal
      wall and the perirectal tissue so that the anorectal wall is bound to the
      surroundings (sacrorectopexy). The results of this retrospective study on 22
      patients proves that this form of transsacral rectopexy in the management of
      rectal prolapse in children is effective (100%), simple and without complications
      compared to other techniques. There were no recurrences and no major morbidity.
      The overall surgical treatment of rectal prolapse in children is briefly
      reviewed.

PMID- 8301468
TI  - Outcome of 21 patients with biliary atresia living more than 10 years.
AB  - The outcome of 21 survivors (8 males, 13 females; age range, 11 to 29 years)
      followed for > 10 years after surgery for biliary atresia are discussed. Of the
      21 patients, 18 with type III disease had hepatic portoenterostomy (Kasai
      operation), and 3 with type I disease had hepaticoenterostomy. Twenty patients
      are alive leading almost normal lives; however, 13 (61.9%) patients did have a
      history of complications, including hemorrhage from esophageal varices in 10,
      from a gastric ulcer or erosion in 3, and from a duodenal ulcer in 2; biliary
      reobstruction in 3; and multiple pulmonary arteriovenous fistulae in 2. Of those
      with complications, 7 required surgery. One died suddenly at the age of 19 years
      of a bleeding gastric ulcer. Liver function is normal in 9 (45.0%) of the 20
      alive patients, 2 (10.0%) have slight hepatic dysfunction, and 9 (45.0%) have
      mild-to-moderate hepatic dysfunction. Liver function is almost normal in 3
      patients who had a history of variceal hemorrhage.

PMID- 8301469
TI  - Vitamin A status in biliary atresia: intestinal absorption and liver storage of
      retinol.
AB  - The vitamin A status of 19 patients with corrected biliary atresia was examined.
      They had been receiving 5,000 IU of oral vitamin A daily postoperatively. Plasma
      vitamin A levels in the nonjaundiced group were almost within normal range,
      whereas those in the jaundiced group were significantly low compared with the
      controls. In the oral vitamin A tolerance test, plasma vitamin A levels increased
      from 33.1 +/- 11.8 to 215.4 +/- 100.7 micrograms/dL in the nonjaundiced group,
      and from 23.1 +/- 10.3 to 209.8 +/- 154.2 micrograms/dL in the slightly jaundiced
      group, at 4 hours after the administration of vitamin A, showing no difference
      between both group and control. In the severely jaundiced group, plasma vitamin A
      levels increased from 13.5 +/- 3.5 to 30.0 +/- 14.6 micrograms/dL, a
      significantly smaller increase compared with controls. However, liver vitamin A
      levels were greater than 20 micrograms/g liver in all patients, irrespective of
      the presence of jaundice. This study suggested that nutritional support to
      facilitate the synthesis of retinol-binding protein may be an important factor in
      addition to vitamin A supplementation.

PMID- 8301470
TI  - Stitch granulomas following inguinal herniotomy: a 10-year review.
AB  - During the years 1982 through 1991, stitch granulomata complicated 15 of 2,447
      inguinal herniotomies. The lesions were diagnosed 3 to 120 months (mean +/- SE,
      2.46 +/- 0.65 years) following surgery. Granulomata were associated with male sex
      (P = .02), emergency herniotomy (P = 0.016), surgery during the neonatal period
      (P = 0.004), and lower mean age at the time of herniotomy (0.79 v 2.84 years, P =
      .000001). In 13 cases, Staphylococcus aureus was recovered either alone or in
      combination with Staphylococcus epidermidis; all patients responded well to
      incision and drainage. Stitch granuloma appears to be associated with male
      herniotomy, emergency surgery, and use of silk sutures.

PMID- 8301471
TI  - Reduction of an incarcerated hernia.

PMID- 8301472
TI  - Specialization medicine in pediatric surgery.

PMID- 8301473
TI  - Infantile hypertropic pyloric stenosis (HPS)

PMID- 8301474
TI  - Perinatal ovarian cyst: a nonsurgical approach.

PMID- 8301475
TI  - Hirschsprung's disease.

PMID- 8301476
TI  - Treatment for necrotizing enterocolitis perforation in the extremely premature
      infant (weighing < 1,000 g)

PMID- 8301477
TI  - Pancreatitis and anomalous union of the pancreaticobiliary ductal system in
      childhood.

PMID- 8301479
TI  - Persistent third branchial apparatus.

PMID- 8301478
TI  - Hypertension associated with skeletal traction in children.

PMID- 8301480
TI  - Branchio-oto-renal syndrome: incidence in three generations of a family.
AB  - It is well known that the persistence of alterations in the normal embryological
      development of branchial arches can lead to preauricular and cervical fistulas
      within a family. However, until 1970, there were no reports of dysplasia
      affecting the branchial, otic, and renal systems (BOR syndrome) with dominant
      autosomic inheritance. The authors report on a family with BOR syndrome of
      different expressivity in three generations, and describe an unusual case of
      bilateral fistulas of the first and second branchial arches in a newborn.

PMID- 8301481
TI  - Main bronchial rupture from blunt trauma in a 2-year-old child.
AB  - The authors report on a 2 year old who sustained a bronchial rupture after a
      motor vehicle accident and was operated on soon after admission. This injury is
      very unusual in young children.

PMID- 8301482
TI  - Survival after gastrointestinal perforation from esophageal atresia and
      tracheoesophageal fistula.
AB  - Management of premature infants with esophageal atresia (EA), tracheoesophageal
      fistula (TEF), and respiratory distress syndrome (RDS) can be one of the most
      challenging aspects in the surgical care of the newborn. Although not common,
      there have been reports of EA, TEF, and RDS with gastric perforation, but an
      associated duodenal perforation has not been reported. Two premature infants
      weighing less than 1,200 g with EA, TEF, and perforation are described. One baby
      developed a gastric perforation and the other a duodenal perforation. Emergency
      thoracotomy and fistula ligation were necessary after gastrostomy placement.
      These patients are the smallest infants reported to survive gastrointestinal
      perforation complicated by EA, TEF, and RDS.

PMID- 8301483
TI  - Pulmonary arteriovenous malformation in the neonate.
AB  - Pulmonary arteriovenous malformation (AVM) is a congenital condition, but because
      the symptoms usually do not occur until middle age, the diagnosis is often
      delayed. The authors report on a neonate, diagnosed at 2 weeks of age, who was
      treated by lobectomy at 35 months of age. This prompted a review of the
      diagnosis, pathophysiology, and treatment of pulmonary AVM. In the literature
      there are approximately 500 cases of pulmonary AVM. Special attention is given to
      the reports involving children. Eight cases have been reported in which the
      diagnosis was made in the first year of life. In two series, a chest
      roentgenogram showed abnormalities in all affected patients. Because of the
      strong association of pulmonary AVM with hereditary telangiectasia (Rendu-Osler
      Weber syndrome), it is recommended that family members of affected patients be
      screened by chest roentgenograms for pulmonary AVM.

PMID- 8301484
TI  - Massive osteolysis of the chest in children: an unusual cause of respiratory
      distress.
AB  - Massive osteolysis, also called Gorham's disease, is an uncommon disease in which
      bone virtually disintegrates and is replaced by vascular fibrous connective
      tissue. The authors treated two children with massive osteolysis of the chest.
      Both conditions responded well to radiation therapy; one even showed evidence of
      reossification. Massive osteolysis should be considered in children who have
      spontaneous hemothorax. The bony structures should be examined for evidence of
      lytic lesions.

PMID- 8301485
TI  - Left-sided gastroschisis.

PMID- 8301486
TI  - Gastric leiomyoblastoma associated with extraadrenal paraganglioma and pulmonary
      chondroma: a new case of Carney's triad.
AB  - Carney's triad is extremely rare. The authors report on a 12-year-old patient who
      had gastric epithelioid leiomyosarcoma, multiple pulmonary chondroma, and
      mediastinal paraganglioma. Thirty-five other cases are reviewed and analyzed.

PMID- 8301487
TI  - Mesenteric lymphadenitis depicted by indium 111-labeled white blood cell imaging.
AB  - An acutely ill child with abdominal pain and concomitant pharyngitis often
      presents a diagnostic challenge. This report describes how indium 111-labeled
      white blood cell imaging helped to clarify the confusing case of a 4-year-old boy
      with fever, pharyngitis, and abdominal pain. The triad of abnormal white cell
      localization in the nasopharynx, cervical lymph nodes, and right lower abdominal
      quadrant supported the diagnosis of a systemic infection rather than
      appendicitis, abscess, or another surgical condition. Mesenteric lymphadenitis
      associated with systemic infection should be included in the differential
      diagnosis of abdominal pain in a child with this clinical presentation.

PMID- 8301488
TI  - Repair of multiple mycotic aortic aneurysms in a newborn.
AB  - Thoracoabdominal aortic and common and internal iliac artery mycotic aneurysms
      resulted from an umbilical arterial catheter in a 3 1/2-week-old boy. He
      underwent staged repair including an 8-mm Gore-tax tube graft, primary repair of
      the common iliac artery aneurysm, and resection of the internal iliac aneurysm.
      His operative and postoperative course was uneventful. He was asymptomatic at 17
      months' follow-up, with equal blood pressure in the upper and lower extremities.
      Magnetic resonance imaging showed no stenoses or recurrent aneurysms at the
      anastomotic sites of the Gore-tex tube graft. Blood supply to his left leg came
      from collaterals, principally a large crossing vessel from the right iliac
      artery. This case represents the first successful aortic replacement in a 5 week
      old with extensive involvement of the thoracoabdominal aorta and its branch
      vessels.

PMID- 8301489
TI  - Successful Kasai operation for biliary atresia in a 9 month old.
AB  - A rare case of a successful Kasai operation for biliary atresia in a 9 month old
      is described. For infants over 6 months of age, there had been no reports of long
      term survival after this procedure.

PMID- 8301490
TI  - Pediatric liver transplantation without red blood cell transfusion.
AB  - The authors report the first case of orthotopic liver transplantation in a
      pediatric patient in whom packed red blood cell transfusion was not required.
      This has obvious advantages in avoiding the infectious complications of
      transfusion. Our patient required 3 U of fresh frozen plasma for treatment of
      preexisting coagulopathy. However, it is possible that, with future advances in
      transfusion therapy, synthetic coagulation factors may be provided in which there
      is no risk of infectious complications, and therefore a truly "bloodless"
      orthotopic liver transplant can be performed.

PMID- 8301491
TI  - Choledochocele: importance of histological evaluation.
AB  - Choledochocele is a rare abnormality of unknown etiology that consists of cystic
      or diverticular dilatations of the intramural part of the common bile duct. The
      authors present a case of choledochocele with a common channel in a 15-year-old
      boy who had a 5-year history of intermittent right upper abdominal pain. In a
      review of the literature, macroscopic variations were noted as well as different
      types of epithelial lining inside the choledochocele. Whereas in young children
      mostly duodenal mucosa is described, biliary tract epithelium and
      undifferentiated epithelium are predominant later on. Etiologically, congenital
      intraluminal duodenal diverticulum should be suggested in relation to the
      pathogenesis of choledochocele. Treatment is total excision and reinsertion of
      both ducts in cases of biliary or undifferentiated epithelium; endoscopic
      sphincterotomy or marsupialization is indicated only when duodenal mucosa covers
      both sides of the choledochocele.

PMID- 8301492
TI  - Anomalous excretion of bile and pancreatic juice in a patient with choledochal
      cyst.
AB  - The authors report the findings of endoscopic retrograde cholangiopancreatography
      in a 1-year-old girl with choledochal cyst; contrast dye injected through the
      common channel was excreted solely through the duct of Santorini. The obstruction
      to the bile and pancreatic juice caused by marked bending of the common channel
      was responsible for the abnormal drainage of bile and pancreatic juice.

PMID- 8301493
TI  - Limy bile syndrome.
AB  - Limy bile syndrome (LBS) is a rare condition in which a radiopaque gallbladder
      and/or bile ducts are noted on plain roentgenograms. LBS is caused by calcium
      carbonate precipitation in the bile and is usually associated with distal biliary
      tract obstruction. The etiology of limy bile syndrome is unclear; however, it may
      be a long-term complication of total parenteral nutrition.

PMID- 8301494
TI  - Congenital cyst of the pancreas.
AB  - The case of a 4-month-old girl with a rare multilocular congenital pancreatic
      cyst is presented, along with radiological/pathological correlation and a review
      of the literature. Congenital cyst of the pancreas is a rare lesion most often
      seen in infant girls, although it may be demonstrated in utero. Conventional
      radiographic signs and clinical symptoms primarily reflect mass effects, whereas
      imaging modalities show the cystic nature of the mass. Although rare, this cyst
      should be considered in the differential diagnosis of fetal and pediatric cystic
      abdominal masses.

PMID- 8301495
TI  - Fatal hemorrhage caused by disease progression after partial splenectomy for type
      III Gaucher's disease.
AB  - An 18-month-old boy with Gaucher's disease, massive hepatosplenomegaly, and
      hypersplenism underwent partial (85%) splenectomy and recovered without
      complication. During the next 4 months, his residual splenic segment showed
      progressive enlargement from 2 to 6 cm below the left costal margin. By this
      time, genetic typing had indicated central nervous system involvement (type III).
      A compatible donor was not available for bone marrow transplantation. Complete
      splenectomy was not recommended despite continued enlargement of the organ into
      the pelvis and across the abdominal midline by 7 1/2 months postoperatively. The
      next week he presented to the emergency room in shock with an hematocrit of 6%
      and a platelet count of 18,000/mm3. During emergency surgery, massive
      intraabdominal hemorrhage was noted from a splenic rupture on the inferior pole
      that was opposite the site of prior division. He died in the operating room
      during attempted splenectomy. This is a report of fatal outcome after partial
      splenectomy for type III Gaucher's disease. Patients with subacute neuronopathic
      disease may not be candidates for subtotal splenectomy.

PMID- 8301496
TI  - Internal displacement of a gastrostomy button: an unusual case of gastric outlet
      obstruction.
AB  - Gastric outlet obstruction caused by gastrostomy tube migration should not occur
      in patients who have gastrostomy buttons. This is the first reported case of
      gastric outlet obstruction caused by internal displacement of a gastrostomy
      button.

PMID- 8301497
TI  - Hypertrophic pyloric stenosis in the newborn.
AB  - Hypertrophic pyloric stenosis is exceedingly rare in newborns as well as patients
      over 6 months of age. These cases likely represent outliers from the normal
      distribution of its clinical presentation. This is a report of pyloric stenosis
      in a newborn. A review of the literature is included.

PMID- 8301498
TI  - Pyeloduodenal fistula: a previously undescribed complication of Stamm
      gastrostomy.
AB  - A variety of complications have been described after placement of a Stamm
      gastrostomy in infants and children, including gastric volvulus, pancreatitis,
      jaundice, gastroduodenal mucosal intussusception with gastric outlet obstruction,
      and even aortogastric fistula. However, this is the first report of pyeloduodenal
      fistula after Stamm gastrostomy in a 4 1/2-month-old boy. The child successfully
      underwent nonoperative therapy; he was treated by withdrawing the gastrostomy
      tube (Foley catheter) from the renal pelvis, bowel rest, and total parenteral
      nutrition. After the case presentation is a brief review of this rare entity,
      with its clinical presentation and pathophysiological differences between adult
      and pediatric cases. Various treatment options, both operative and nonoperative,
      are also described.

PMID- 8301499
TI  - Preampullary congenital duodenal obstruction in a father and son.
AB  - This is the report of an infant seen on June 25, 1960 with preampullary total
      duodenal obstruction caused by a combined annular pancreas and duodenal stenosis
      above the ampulla. A gastroduodenostomy was performed. In December 1989, he
      fathered a 1,700-g boy with preampullary duodenal atresia. A duodeno-duodenostomy
      was performed successfully by the same pediatric surgeon. Second-generation
      duodenal obstruction is rare; to our knowledge, there are no other cases.

PMID- 8301500
TI  - Cystic duodenal duplication: staged management in a premature infant.
AB  - Cystic duplication of the duodenum is a rare anomaly of the gastrointestinal
      tract. Patients may present in early childhood with symptoms of upper intestinal
      obstruction. Successful, staged management of a cystic duodenal duplication in an
      880-g infant is described.

PMID- 8301501
TI  - Giant jejunoileal duplication: prenatal diagnosis and complete excision without
      intestinal resection.
AB  - A 7-week-old child presented to the pediatrician after persistent vomiting and
      abdominal distension developed. Intestinal dilatation had been detected in utero.
      Emergency ultrasonography showed only small bowel dilatation. There were no signs
      of intestinal obstruction; however, complete intestinal malrotation was
      demonstrated by an upper gastrointestinal series and barium enema. Intestinal
      duplication was also suspected, and emergency laparotomy was performed. A 70-cm
      long jejunoileal duplication was found and successfully dissected free from the
      normal small bowel and excised without intestinal resection-anastomosis. The
      authors describe this unique case and the surgical technique for the treatment of
      small bowel duplications.

PMID- 8301502
TI  - A 3-year survivor of near-total intestinal aganglionosis.
AB  - A newborn girl had no ganglion cells beyond 2 cm distal to the ligament of
      Treitz. The proximal jejunum was dilated. A jejunostomy constructed 46 cm distal
      to the ligament of Treitz functioned. A 28-cm jejunal segment was myectomized to
      augment enteral feeding. For almost 1 year she has been on enteral feedings only,
      and her body size has been in the 75th percentile.

PMID- 8301503
TI  - Adenocarcinoma of the rectum in a 15 year old.
AB  - A 15 year old with Duke's C2 adenocarcinoma of the rectum was treated with a
      sphincter-saving surgical resection and adjuvant chemotherapy and radiation. The
      patient is alive and has been disease-free for over 5 years. Adenocarcinoma of
      the colon is a virulent disease in children and has a poor prognosis. The reasons
      for this are explored, and a literature review is included.

PMID- 8301504
TI  - Giant popliteal false aneurysm in an 8-year-old child.
AB  - Aneurysms of the arterial system are rare in children. Aneurysms of the popliteal
      artery are extremely rare in the pediatric population; the majority of these
      occur after penetrating trauma. The authors report the presentation, evaluation,
      and successful surgical repair of a giant popliteal false aneurysm found in an 8
      year-old girl presumably secondary to blunt trauma.

PMID- 8301505
TI  - Pigmented villonodular synovitis in a child.
AB  - The authors present a case of pigmented villonodular synovitis (PVNS) in an
      adolescent with monarticular involvement of the ankle and without congenital
      anomalies or sibling involvement. Its rarity in the ankle and in childhood is
      discussed; a review of the clinical, radiological, and pathological features of
      PVNS is presented.

PMID- 8301506
TI  - Inverted papilloma of the urinary bladder in a boy.
AB  - Inverted papilloma of the urinary bladder is not uncommon in adults. In children,
      only two cases had been reported to our knowledge. Another pediatric case is
      described herein, in which the lesion occurred in a 9-year-old boy; he is the
      youngest patient reported to have this condition.

PMID- 8301507
TI  - Cystic neuroblastoma in a newborn.
AB  - A neuroblastoma that presented as an adrenal cyst in a newborn infant is
      described. This is an extremely unusual presentation for neuroblastoma; it
      emphasizes the need for a high degree of suspicion when evaluating any abdominal
      mass in the newborn.

PMID- 8301508
TI  - Prenatal diagnosis and treatment strategy for congenital mesoblastic nephroma.
AB  - By means of the recent sophisticated technology regarding prenatal diagnosis,
      congenital mesoblastic nephroma (CMN) has become detectable before birth, or at a
      younger age than previously. Recently we treated an infant with a huge CMN in
      whom fetal asphyxia and tumor rupture occurred during the perinatal observation
      period after prenatal detection. Emergency surgery was required, and the
      postoperative course was complicated. The treatment strategy of the perinatal
      care team should focus on (1) reliable maternal transportation (2) continuous
      monitoring of fetal condition including cardiovascular status, (3) control of
      polyhydramnios to avoid premature labor, and (4) elective surgery at a stable or
      stabilized condition. Emergency surgery should be performed when circulatory
      disturbance, respiratory distress, and/or impending rupture are suspected.

PMID- 8301509
TI  - Prepubic dermoid sinus: possible variant of dorsal urethral duplication (Stephens
      type 3).
AB  - The authors present the case of 4-month-old girl with a midline prepubic sinus
      extending from the skin overlying the pubis to the superior surface of the
      bladder, and continuing to the umbilicus via the median umbilical ligament. The
      distal portion of the exicised sinus was surrounded by concentric bundles of
      collagen and smooth muscle with minimal inflammatory infiltrates, which suggests
      a developmental origin. According to Stephens' classification, the sinus appears
      to be a variant of dorsal urethral duplication of Stephens type 3.

PMID- 8301510
TI  - Paratesticular neuroblastoma with N-myc activation.
AB  - The authors describe a case of disseminated neuroblastoma discovered as a
      paratesticular tumor in a 7-month-old boy. The ectopic adrenal tissues adjacent
      to the paratesticular tumor and multiple lesions in the adrenal gland and skin
      suggested the possibility of multifocal primary tumors. Although infantile
      neuroblastoma diagnosed at less than 1 year of age generally responds well to
      treatment irrespective of distant metastases, metastases developed, and the boy
      died of disease within 7 months. All multiple lesions had amplification and
      overexpression of the N-myc protooncogene, which might explain the aggressive
      phenotype of this rare case.

PMID- 8301512
TI  - Mesenteric fibromatosis.
AB  - The authors present the case of a 13-year-old boy in whom, after irradiation for
      Hodgkin's disease and exploratory laparotomy, mesenteric fibromatosis developed.
      The "tumor" was resected, and 1 year postoperatively the patient is well.

PMID- 8301511
TI  - Accessory limb attached to the back.
AB  - The authors report on a newborn with an accessory malformed leg attached to the
      back. The limb was associated with a teratomatous mass adjacent to its attachment
      site. The embryology and nomenclature of this malformation is discussed briefly.

PMID- 8301513
TI  - Gastric carcinoma in children.
AB  - Primary gastric carcinoma accounts for only 0.05% of pediatric gastrointestinal
      malignancies. The pattern, presentation, and location of childhood gastric
      carcinoma are similar to those of adult gastric carcinoma. Diagnosis is based on
      a high index of suspicion in children who present with symptoms mimicking acid
      peptic disease. Delay in diagnosis is common and avoided by early upper
      gastrointestinal radiography and endoscopy with biopsy. Surgical therapy alone
      may prolong survival but thus far it has proven only palliative. The role of
      chemotherapy and radiation in gastric carcinoma is still not well defined,
      although some new studies in adults may support the use of etoposide,
      doxorubicin, and cisplatin as primary therapy or combined with surgery and
      radiation. Long-term survival in children is rare. We present the case of a 3
      year survivor, free of disease, treated with resection and chemotherapy.

PMID- 8301514
TI  - Giant thymolipoma in a child.
AB  - Thymolipoma, a rare benign mediastinal tumor, was found in a 6-year-old boy.
      Computed tomography scans, magnetic resonance imaging, and angiography of
      internal thoracic artery confirmed the diagnosis before surgery.

PMID- 8301515
TI  - Omental lipoblastoma.
AB  - Lipoblastoma is a rare benign neoplasm of fetal fat tissue. To our knowledge,
      only 73 cases have been reported in the English literature. This is an unusual
      case of an omental lipoblastoma in a 7-month-old girl.

PMID- 8301516
TI  - Laparoscopic-guided gastropexy for intermittent gastric volvulus.
AB  - A 12-year-old girl with acute gastric volvulus associated with severe scoliosis
      and neurological impairment did well initially with nasogastric tube
      decompression. To prevent recurrence, anterior gastropexy was performed using
      percutaneous sutures through the abdominal wall and stomach with the gastroscope
      in place. Simultaneous laparoscopic guidance was used to ensure that the stomach
      was fixed in a nonrotated position. One year later, volvulus has not recurred.
      This method of gastropexy is indicated only in children with intermittent gastric
      volvulus who do not have an underlying abnormality such as diaphragmatic hernia.

PMID- 8301517
TI  - An absent right and persistent left superior vena cava in an infant requiring
      extracorporeal membrane oxygenation therapy.
AB  - A persistent left superior vena cava (PLSVC) is the most common anomaly of the
      major veins. However, an absent right superior vena cava and PLSVC is much less
      common; fewer than 100 cases have been reported in the world literature in
      patients with situs solitus. This rare variation was encountered in a newborn
      requiring extracorporeal membrane oxygenation (ECMO) for meconium aspiration and
      interfered with venous cannulation. The anomaly was not suspected before an
      unusual cannula position was observed on the chest radiograph, and it was
      confirmed by bedside venography. Adequate venous cannulation was obtained through
      the anomalous vessel using a flexible catheter, allowing for an uneventful ECMO
      course. The epidemiology and embryology of this incidental anomaly are reviewed,
      and the methods used to circumvent the difficulties it presented in this case are
      described.

PMID- 8301518
TI  - Treatment of complicated congenital splenic cysts.
AB  - Although rare in occurrence, the potential for congenital splenic cysts to
      enlarge, rupture, or become infected has been well documented. Presented is the
      case of a 13-year-old boy with an infected epidermoid cyst of the spleen, which
      presented as a solitary splenic abscess. The entity has traditionally been
      treated by splenectomy or, more recently, percutaneous drainage. However, given
      the inability of percutaneous drainage or sclerotherapy to permanently obliterate
      congenital splenic cysts, the authors managed this condition with percutaneous
      drainage and interval partial splenectomy. This achieves complete removal of the
      lesion while preserving splenic function.

PMID- 8301519
TI  - Segmental dilatation of the ileum: an uncommon cause of neonatal intestinal
      obstruction.
AB  - Two cases of congenital segmental dilatation of the ileum are reported. In both
      cases additional abnormal segments of bowel were not diagnosed during the initial
      laparotomy, and further surgical exploration was required. Consideration of this
      entity in the differential diagnosis of neonatal intestinal obstruction may
      enable definition of the optimal site for bowel resection and anastomosis.

PMID- 8301520
TI  - Preservation of the ileocecal valve and right colon in total colonic
      aganglionosis.
AB  - A new surgical technique for the treatment of total colonic aganglionosis is
      described. Preservation of the right colon and the ileocecal valve is possible by
      performing an end-to-back anastomosis between a prececal short ileum segment and
      the uneffected ileum, and by creating a side-to-side anastomosis between an
      isolated ileal loop and the right colon. The ileorectal anastomosis is performed
      with a curved EEA 21 circular stapler (USSC, Norwalk, CT). After a neonatal
      ileostomy, the operation is performed as a one-stage procedure. The advantage of
      preserving the right colon and the ileocecal valve is discussed.

PMID- 8301521
TI  - Survival following gastrointestinal perforation from esophageal atresia and
      tracheoesophageal fistula.

PMID- 8301522
TI  - Evaluation of autoantibodies to brain proteins in patients with AIDS dementia
      complex.
AB  - A high frequency of autoantibodies to brain proteins has been reported in HIV-1
      positive patients. However, the specificity of this response has not been
      characterized. Using homogenized tissue from three normal brains, the presence of
      autoantibodies to human brain proteins was analyzed in 16 HIV-1-positive patients
      with AIDS dementia complex (ADC), 10 HIV-1-positive patients without ADC, 10
      patients with multiple sclerosis, 10 patients with juvenile rheumatoid arthritis,
      and 10 normal controls. Although antibodies to various brain proteins were
      detected in sera from one-third HIV-1-infected individuals with or without ADC,
      the proteins recognized were different among different brains. Only one ADC
      patient had consistent seroreactivity to a 50-kDa brain-specific protein. Our
      results indicate that autoantibodies to brain proteins are infrequently present
      in patients with ADC.

PMID- 8301523
TI  - Differential expression of tumor necrosis factor alpha and interleukin 1 beta
      compared with interleukin 6 in monocytes from human immunodeficiency virus
      positive individuals measured by polymerase chain reaction.
AB  - Expression of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1
      beta), and interleukin 6 (IL-6) was evaluated in unstimulated peripheral blood
      monocytes obtained from human immunodeficiency virus-positive (HIV+) individuals
      using a reverse transcription-polymerase chain reaction (RT-PCR) method. In all,
      40 subjects were included--13 asymptomatic, 11 with ARC, seven with AIDS, and
      nine HIV- controls. Of the asymptomatic individuals, 85% were positive for TNF
      alpha and IL-1 beta compared with only 27% of the ARC and 42% of the AIDS
      patients. Expression of IL-6 message was observed in lesser proportions, with no
      significant differences among disease states. Quantitation of IL-1 beta and TNF
      alpha mRNA from the positive samples fell into two categories, low responders
      (six of 17), with < 5,000 copies of IL-1 beta and TNF alpha mRNA, and high
      responders (11 of 17), with > 5,000 copies per 10 pg of total cellular RNA. There
      was no correlation of mRNA detection or concentration with CD4+ cell number or
      beta 2-microglobulin levels. However, the levels of mRNA, but not its presence
      alone, were positively correlated with neopterin levels. The data show
      differential cytokine regulation in monocytes, observed as an increase in the
      expression of TNF alpha and IL-1 beta compared with IL-6 in HIV+ patients. Our
      report also emphasizes the utility of an RT-PCR system in analyzing multiple
      cytokine transcript levels in small amounts of clinical materials.

PMID- 8301524
TI  - CD4-modified synthetic peptides containing phenylalanine inhibit HIV-1 infection
      in vitro.
AB  - Phenylalanine-containing peptides from CD4 were synthesized based on chemical
      similarity with active CD4(81-92)-benzylated peptides. The synthetic peptide
      FYIFFVEDQKEEDD blocked the binding of gp120 to CD4 and inhibited 50% human
      immunodeficiency virus (HIV)-induced syncytia formation at a concentration (IC50)
      of approximately 40-50 microM and HIV p17 expression with an IC50 of
      approximately 67 microM. The peptide is not toxic to cells in vitro. Moreover,
      acute toxicity studies carried out in Swiss mice showed the peptide to be
      nontoxic at a dose of 2,000 mg/kg. This phenylalanine-substituted CD4 peptide may
      prove to be useful in the treatment of AIDS.

PMID- 8301525
TI  - Fetal toxicity of zidovudine (azidothymidine) in Macaca nemestrina: preliminary
      observations.
AB  - The objective of this study was to determine the dam, fetal, and infant toxicity
      of zidovudine (AZT) administered to pigtailed macaques during pregnancy. Pregnant
      macaques were administered AZT (1.5 mg/kg/dose every 4 h) or water via gastric
      catheter throughout pregnancy. AZT concentration and hematological changes were
      monitored in the dam, and fetal growth was monitored via ultrasound. Infant
      hematocrit was assessed at birth, and the neurological, perceptual, and motor
      development of the offspring were assessed for 9 to 10 months. Twelve pregnancies
      were brought to term. Mean plasma concentrations of AZT were comparable to those
      in human studies. Hemoglobin dropped significantly in pregnant dams and remained
      low, whereas platelets increased during treatment but returned to normal before
      the end of the study. There were no significant differences in any ultrasound
      measure of fetal growth, and AZT-exposed infants exhibited little behavioral
      delay or impairment. We predict no significant toxic effects of prenatal AZT
      exposure at this dosage in humans.

PMID- 8301526
TI  - Persistent arthralgia and its association with HIV infection in Rwanda.
AB  - A prospective study of persistent arthralgia was carried out on 331 consecutive
      female patients admitted to the Department of Internal Medicine of the Centre
      Hospitalier de Kigali in Kigali, Rwanda. The aim of this study was to determine
      its association with HIV-1 infection and to describe its clinical
      characteristics. Ten additional HIV-1-seropositive patients with this condition
      attending the outpatient clinic were also included in the clinical study.
      Persistent arthralgia was significantly more common in HIV-1-seropositive
      hospitalized patients (14 of 209, 6.7%) than in HIV-1-seronegative hospitalized
      patients (one of 122, 0.8%; p = 0.02) and had a specificity and a positive
      predictive value for HIV-1 infection of 99.1% and 93.3%, respectively. HIV-1
      related persistent arthralgia, studied in 24 patients in early as well as late
      stages of HIV-1 infection, commonly affected several and mainly large joints, was
      mostly distributed symmetrically, and was usually relieved with nonsteroidal
      antiinflammatory drugs. Recurrencies were noted in eight patients. In areas
      highly endemic for HIV-1, persistent arthralgia should be considered a probable
      manifestation of HIV-1 infection, and although it is uncommon, it can be regarded
      as a predictor of HIV-1 infection.

PMID- 8301527
TI  - HIV-1 and bleach.

PMID- 8301528
TI  - HIV infection among women in the Army Reserve Components.
AB  - There is little information regarding the extent of HIV infection among women.
      Since late 1985, members of the Army Reserve Components have been routinely
      tested for HIV, providing an opportunity to measure directly the prevalence and
      incidence density of infection in a military-associated population with limited
      military contact. We evaluated the prevalence among 122,195 women, and directly
      measured the incidence density among 96,001 women followed for 247,872 person
      years. The overall prevalence was 0.65 (per 1000), and the incidence density was
      0.12 (per 1000 person years follow-up). Several demographically defined groups,
      including minority women, had elevated levels of infection. The incidence
      densities of infection between early and late in the testing program were
      compared, and no evidence of acceleration or deceleration was observed.

PMID- 8301529
TI  - Prevalence of antibody to the human immunodeficiency virus among clinical
      laboratory specimens: findings from a survey of primary care physicians.
AB  - To evaluate human immunodeficiency virus type 1 (HIV-1) infection among patients
      of primary care physicians, we performed anonymous, unlinked HIV-1 antibody
      testing on leftover blood specimens submitted to 10 large commercial clinical
      laboratories for complete blood cell count or hematocrit determination, the most
      commonly ordered diagnostic tests. From January through August 1990, 55,613
      specimens submitted by general internists, pediatricians, and family
      practitioners were sampled; 1,104 (2.0%) had HIV-1 antibody. Seroprevalence among
      the laboratories varied 50-fold, from 0.3 to 12.4%. The HIV-1 prevalence at each
      laboratory was not always consistent with the AIDS incidence in the area served
      by the laboratory. Overall the seroprevalence was almost eight times higher in
      men (3.9%) than in women (0.5%). Specimens from seropositive persons, especially
      from men, were unevenly distributed among the physician practices; only three
      practices submitted approximately 50% of all specimens from seropositive men.
      These data indicate that a few physicians treat the majority of HIV-1-infected
      primary care patients. The HIV-1 prevalence among specimens at a clinical
      laboratory is thus determined by whether few physicians submit specimens to that
      laboratory. These results could be of use, for instance, in analyzing proposals
      to mandate physician reporting of HIV-1 infection. The high HIV-1 prevalence
      among laboratory specimens underscores the potential for exposure to HIV-1
      infected blood by clinical laboratory personnel and emphasizes the need for
      universal precautions for all blood specimens.

PMID- 8301530
TI  - HIV incidence among needle exchange participants: estimates from syringe tracking
      and testing data.
AB  - This paper develops a statistical procedure for estimating the HIV infection rate
      among needle exchange clients without using any self-reported information.
      Instead, data are accumulated by following the distribution and return of
      sequentially labeled syringes and by testing a sample of returns for the presence
      of HIV-1 proviral DNA using polymerase chain reaction. For each drug injector in
      the sample, a maximum likelihood change point model is constructed to determine
      if a statistically significant upward shift in the fraction of needles testing
      HIV positive is evident, as would occur if the drug injector in question became
      infected. A second maximum likelihood model is formulated to estimate the HIV
      incidence rate among needle exchange participants by aggregating the individual
      change point results. When these methods are applied to the syringe tracking and
      testing data collected to evaluate the legal needle exchange program in New
      Haven, Connecticut, the maximum likelihood incidence estimate equals zero, with a
      95% confidence interval of 0-10.2 new infections per 100 drug injectors per year.
      Given these data, we cannot reject the null hypothesis that no new infections
      have occurred among needle exchange participants between November 1990 and May
      1992.

PMID- 8301531
TI  - Sexual behavior and sexual identity in male injection drug users.
AB  - Sexual behavioral data from a survey of 396 male drug injectors showed that 301
      (76%) were behavioral heterosexuals, 49 (12.45%) were bisexuals, and 46 (11.6%)
      were homosexuals over the previous 5 years. Among those sexually active during
      the 6 months before the interview, bisexuals were similar to heterosexuals and
      homosexuals in reporting two or more female or male partners, respectively.
      Overall, almost three fourths of the bisexuals had two or more sexual partners.
      Bisexuals were also similar to heterosexuals in reported heterosexual and
      intercourse (16 and 15%, respectively), and to homosexuals in reported homosexual
      insertive anal intercourse (33 and 54%, respectively). They were less likely than
      heterosexuals to engage in vaginal and insertive oral sex with women and than
      homosexuals to practice receptive and and oral sex with men. The three groups all
      practiced high levels of unprotected sex. Almost half the behavioral bisexuals
      identified themselves as heterosexuals. Self-identified heterosexuals in the
      sample were less likely than self-identified gays or bisexuals to state they
      reduced sexual risk; however, reported condom use was low for all three groups.
      With human immunodeficiency virus infection rates of 54% (21 of 39) for
      behavioral homosexuals, 24% (11 of 45) for bisexuals, and 9% (24 of 260) for
      heterosexuals, these findings indicate an urgent need for more effective sexual
      risk reduction among injection drug users and their partners.

PMID- 8301532
TI  - Association of HTLV-I antibody profile of asymptomatic carriers with proviral DNA
      levels of peripheral blood mononuclear cells.
AB  - The human T-lymphotropic virus type I (HTLV-I) antibody profile of 216
      asymptomatic carriers in Miyazaki, Japan, was analyzed in conjunction with the
      HTLV-I proviral DNA levels in their peripheral blood mononuclear cells (PBMC)
      determined by the semiquantitative polymerase chain reaction (PCR) method. The
      geometric mean HTLV-I titer by particle agglutination assay (PA) of 58 subjects
      (27%) with a high DNA level was 1:1, 240; 94 (44%) with a medium DNA level,
      1:740; 38 (18%) with a low level, 1:476; and, 26 (12%) with an undetectable
      level, 1:263. Moreover, when the subjects were divided into four groups according
      to titer from high to low, the correlation between DNA level and antibody titer
      level was highly significant (p < 0.0001). HTLV-I antibody subclass by Western
      blot (WB) was determined for 78 randomly selected samples from these carriers.
      Immunoglobulin (Ig) M antibody was detected in 35 (45%). The mean PA antibody
      titer was higher in carriers with IgM antibody than in those without, at each
      detectable proviral DNA level. These findings suggest that HTLV-I antibody titer
      is related to proviral DNA level and also to the presence of IgM antibodies among
      those with proviral DNA of the same level. Seven carriers (9%) were negative for
      IgG antibody by WB, among whom the proviral DNA level was low or undetectable and
      the PA titer was also low. Three of these were positive only for IgM antibody.

PMID- 8301533
TI  - Cervicovaginal virus secretion in HIV-infected women.

PMID- 8301534
TI  - HIV-1 inactivation by bleach.

PMID- 8301535
TI  - HTLV-I/II seroprevalence and coinfection with other pathogens in blood donors in
      Buenos Aires.

PMID- 8301536
TI  - High risk of developing toxoplasmic encephalitis in AIDS patients seropositive to
      Toxoplasma gondii.

PMID- 8301537
TI  - Occupational HIV infection following a stylet injury.

PMID- 8301539
TI  - [Synthesis of imidazo[1,2-a]pyridine derivatives and their reactions].
AB  - By the reaction of 2-benzoylmethylimidazoles (1a, b) with polarized olefins (2,
      3) in the presence of K2CO3, the corresponding imidazo[1,2-a]pyridine derivatives
      (4, 5) were obtained. Methylsulfinylimidazopyridine derivative (7) obtained by
      the reaction of 5b with m-chloroperbenzoic acid (m-CPBA), easily underwent
      nucleophilic substitution to give the corresponding substituted compounds (8a-
      e). The substitution of chloroimidazopyridine derivative (11) with nucleophiles
      produced the corresponding substituted compounds (12a--d).

PMID- 8301538
TI  - [The characterization of human cdc2 kinase and CDK2].
AB  - p34cdc2 kinase plays a key role in the initiation of mitosis. The activity of
      this kinase requires the binding of a protein, named cyclin, to it. The kinase
      forms a heterodimer with cyclin. Cyclin A or B is the counterpart of this
      complex. The differences in the activity between cyclin A/cdc2 kinase and cyclin
      B/cdc2 kinase have not been cleared. In recent years, the other cdc2-like kinases
      were identified. One of them was CDK2 (cyclin dependent kinase 2). CDK2 could
      rescue the defect of the budding yeast CDC28 mutation, which arrested the cells
      at a point named START, in G1 phase. Then, CDK2 was thought to be worked at G1
      through S phase in a cell cycle, but the details on the role of this kinase has
      not been cleared so far. In this study, we separated the human cyclin A/cdc2
      kinase, cyclin B/cdc2 kinase and CDK2, each other by use of column
      chromatography, and characterized the each kinase. These kinases had the same
      substrate specificities when the synthesized peptides were tested. They
      phosphorylated the threonine residue in the sequence -Thr-Pro-Lys-Lys-Ala- but
      hardly phosphorylated threonine residue the sequence -Thr-Pro-Lys-Ala-Lys-. They
      had some differences in the substrate-preference when the native proteins were
      tested. In a cell cycle of human cells, the activity of cdc2 kinase increased at
      G2/M phase and the activity of CDK2 was high from S through M phase. These data
      suggested that cdc2 kinase works at the transition from G2 to M phase and that
      CDK2 works from G1 through G2/M phase. They could phosphorylate different protein
      substrates having the common phosphorylated sequence -Thr-Pro-X-Lys-.

PMID- 8301540
TI  - [Protective effects of Taiwan crude drugs on experimental liver injuries].
AB  - Protective effects of 41 Taiwan crude drugs on rat hepatic injuries caused by
      carbon tetrachloride (CCl4) and alpha-naphthylisothiocyanate (ANIT) were
      investigated. The methanol extracts of Elephantopi Herba and Lonicerae Flos
      inhibited the release of intrahepatic enzymes and histological changes by CCl4.
      The methanol extracts of Canarii Radix, Arecae Pericarpium, Cynomorii Caulis,
      Polygoni Cuspidati Radix, Phyllodii Herba, Junci Caulis Medulla, Rubiae Herba and
      Rhinacanthi Herba protected the hepatic injury by ANIT. Among them, the water
      extracts of Cymorii Caulis and Junci Caulis Medulla showed higher protective
      potency than the methanol extracts. And them this two crude drugs also protected
      the cholestasis by ANIT.

PMID- 8301541
TI  - [A simultaneous determination of daidzin and puerarin and determination of
      daidzein in Oriental pharmaceutical decoctions containing puerariae radix by ion
      pair high-performance liquid chromatography].
AB  - A simple and precise method was established for the simultaneous determination of
      daidzin and puerarin and the determination of daidzein in oriental pharmaceutical
      decoctions containing Puerariae Radix using high-performance liquid
      chromatography with tetra-n-heptylammonium bromide (THA) as an ion-pair reagent.
      Daidzin and puerarin were eluted within 45 min without interference with co
      existing components using an ODS column and a mixture of 10 mM phosphate buffer
      (pH 6.5)-methanol (68:32) containing 5 mM THA as a mobile phase. Daidzein was
      eluted within 35 min without interference with co-existing components using an
      ODS column and a mixture of 10 mM phosphate buffer (pH 6.5)-acetonitrile (72:28
      or 68:32) containing 5 mM THA as a mobile phase.

PMID- 8301542
TI  - [A simultaneous determination of honokiol and mangolol in Oriental pharmaceutical
      decoctions containing magnolia bark by ion-pair high-performance liquid
      chromatography. II].
AB  - A simple method using ion-pair high-performance liquid chromatography was
      established for the rapid and precise determination of honokiol(3',5-di-2
      propenyl-1,1'-biphenyl-2,4'-diol) and magnolol(5,5'-di-2-propenyl-1,1'-biphenyl
      2,2'-diol) in eighteen species of oriental pharmaceutical decoctions containing
      Magnolia bark. An ODS column and a mixed solvent system of water involving 10 mM
      tetra-n-amyl-ammonium bromide (TAA) and acetonitrile (4:6) as a mobile phase were
      used for the separation. Honokiol and magnolol were eluted without interference
      of other coexisting components within 12 min.

PMID- 8301543
TI  - A dose-response analysis of the subjective, psychomotor and physiological effects
      of intravenous morphine in healthy volunteers.
AB  - The purpose of this study was to characterize the subjective, psychomotor and
      physiological effects of morphine in healthy volunteers. Subjects (10 males and 2
      females) without histories of opiate dependence were injected in an antecubetal
      vein with 0, 2.5, 5.0 or 10 mg/70 kg of morphine, by using a randomized, double
      blind, cross-over design. Subjective effects, psychomotor performance and
      physiological measures were assessed immediately before the injection and for up
      to 5 hr afterward. Morphine increased the Pentobarbital-Chlorpromazine-Alcohol
      Group, Amphetamine, the Lysergic Acid Diethylamide and the Morphine-Benzedrine
      Group scores and decreased Benzedrine Group scores on the Addiction Research
      Center Inventory. Increased visual analog scale ratings of "stimulated," "high,"
      "sedated," "coasting or spaced out" and "drunken" were also obtained. On an
      opiate adjective checklist, subjects reported increased ratings of "flushing,"
      "dry mouth" and "tingling." Drug liking was not significantly altered by
      morphine, but there was substantial intersubject variability with this measure.
      Some aspects of psychomotor performance (reaction time, Digit Symbol Substitution
      Test and Maddox Wing) were impaired by morphine; however, eye-hand coordination
      was not. Miosis was induced by morphine. Most effects of morphine were dose
      related, some effects peaked soon after morphine injection (e.g., increased
      stimulated and high ratings) and dissipated gradually, whereas other effects did
      not peak until later into the session (sedation or exophoria). Our results are
      fairly consistent with other studies examining morphine effects in healthy
      volunteers, and also indicate that the profile of morphine effects differ between
      healthy volunteers and those with a history of opiate dependence.

PMID- 8301544
TI  - Pentoxifylline and meclofenamic acid treatment reduces clinical manifestations in
      a murine model of AIDS.
AB  - C57/BL/6 mice infected with LP-BM5 MuLV virus developed an AIDS-like disease
      (MAIDS) with splenomegaly, leukopenia, thrombocytopenia, anemia, decreased
      numbers of helper/inducer and suppressor/cytotoxic T-cells and decreased
      production of interferon alpha. We have shown previously that HIV-associated
      Kaposi's sarcoma tissue contains high levels of prostaglandin E2 (PgE2), and this
      inhibits interferon synthesis through a cAMP-dependent second-messenger process.
      In this study we treated groups of MAIDS-infected mice with combinations of
      pentoxifylline, an agent which increases cAMP and inhibits phosphodiesterases,
      and sodium meclofenamic acid, a PgE2 inhibitor. Treated mice showed: 1)
      significantly higher total leukocyte and platelet counts, 2) higher total L3T4+
      (helper/inducer) and Lyt-2+ (suppressor-cytotoxic) T-cell population. Pathologic
      examination also showed significantly less hepatosplenomegaly and lymphadenopathy
      in animals treated with pentoxifylline and meclofenamic acid. Partly, PgE2
      induced suppression of interferon alpha production may mediate expression of
      retrovirus infection in this murine model of AIDS.

PMID- 8301545
TI  - Serotonin-induced pulmonary responses are mediated by the 5-HT2 receptor in the
      mouse.
AB  - C57BL/6 mice exhibit acute transient decreases in lung conductance (GL) and
      dynamic compliance (Cdyn) after intravenous administration of serotonin (5-HT).
      To identify the specific agonist receptor subtypes responsible for this
      bronchoconstriction, we measured changes in pulmonary function in C57BL/6 mice in
      response to intravenous infusion of 5-HT receptor subtype-selective agonists and
      to 5-HT in the presence of antagonists selective for the 5-HT2 or 5-HT3 receptor
      subtypes. Agonists selective for the 5-HT1A/1B/1D or 5-HT3 receptor subtypes
      induced minimal or undetectable pulmonary responses, whereas infusion of alpha
      methyl-5-hydroxytryptamine, a 5-HT2 receptor-selective agonist, led to dose
      related decreases in Cdyn and GL. The selective 5-HT3 receptor antagonist,
      LY278584 maleate, (1.0 mg/kg i.v.) caused no detectable reduction in the response
      to 100 micrograms/kg of 5-HT. In contrast, treatment with the 5-HT2 receptor
      antagonist LY53857 (10 micrograms/kg i.v.) resulted in a significant diminution
      of the pulmonary response observed after infusion of 100 micrograms/kg of 5-HT.
      Dose-response relationships were established for 5-HT in experiments in which
      each mouse was treated with a single dose of 5-HT without antagonist or after
      LY53857. Compared with responses to doses of 5-HT of more than 100 micrograms/kg
      in the absence of antagonist, pulmonary responses to 5-HT after infusion of 10
      micrograms/kg of LY53857 were significantly reduced; 100 micrograms/kg of LY53857
      nearly abolished the responses to all doses of 5-HT.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8301546
TI  - Morphine-6-beta-D-glucuronide respiratory pharmacodynamics in the neonatal guinea
      pig.
AB  - Morphine-6-beta-D-glucuronide (M6G) is a metabolite of morphine with opioid
      activity in adults. No data are available, however, on the developmental
      pharmacology of M6G including investigation of the respiratory effects of M6G in
      the neonate. A randomized, placebo-controlled study comparing the time-action,
      dose-response and potency of the respiratory effects of M6G to morphine was done
      using a nonanesthetized neonatal guinea pig model and a noninvasive computerized
      plethysmograph technique. Respiration was measured while the neonate breathed
      room air followed by 5% CO2 in air. M6G (0.5-5.0 mg/kg) and morphine (1.5-15
      mg/kg) administered subcutaneously decreased ventilation in 3-, 7- and 14-day-old
      neonatal guinea pigs given a 5% CO2 challenge. During CO2 inhalation, time-to
      peak action for M6G occurred 21 min later than for morphine. At maximal
      ventilatory depression on day 3, a dose of 1.5 mg/kg morphine or M6G decreased
      minute ventilation while breathing 5% CO2 by 30% compared to placebo. Ventilation
      also decreased as a function of age in both placebo and drug-treated animals. The
      percent respiratory depression relative to placebo remained constant for a given
      dose of morphine as the neonate aged, but not for M6G, which increased in
      potency. M6G was equipotent to morphine on day 3 after birth, but was 8-fold more
      potent by day 7. This increase in potency persisted through day 14. The increased
      potency of M6G that accompanies aging may be caused by either a change in M6G
      disposition or a change in opioid receptors during development of the neonatal
      guinea pig.

PMID- 8301547
TI  - Serotoninergic receptor subtype in coronary artery smooth muscle from young and
      atherosclerotic rabbit.
AB  - In rabbits fed with hypercholesterolemic diet the normal coronary vasodilator
      response to serotonin is replaced by vasoconstriction sensitive to 5HT2 receptor
      blockade. These experiments were designed to determine the receptor subtype
      involved in the contractile response of large isolated coronary arteries (without
      endothelium) taken from control and atherosclerotic rabbits. In both tissues the
      agonists' rank potency was 5-carboxamidotryptamine > serotonin (5HT) >
      sumatriptan > 8-OHDPAT: (+/-)-8-Hydroxydipropylaminotetralin HBr > 2
      methylserotonin. In arteries from young rabbits, 5HT and sumatriptan induced
      contractions which were not influenced by ketanserin up to 3 x 10(-8) M. However,
      the 5HT2 antagonist at the concentration of 10(-6) M induced a significant
      rightward shift of the concentration-response curves. The contractions to the two
      serotoninergic agonists were competitively inhibited by methiothepin. NAN 190, a
      5HT1A antagonist, LY 53857, a 5HT1C and 5HT2 antagonist, cyanopindolol, a 5HT1A
      and 5HT1B antagonist and ICS 205-930, a 5HT3 and 5HT4 antagonist (up to 10(-6) M)
      did not inhibit the contractile response to 5HT. Rauwolscine (10(-6) M)
      significantly shifted the concentration-response curves to the two agonists. Very
      similar results were obtained in coronary arteries from atherosclerotic rabbits.
      These data demonstrate that in rabbit epicardial coronary artery smooth muscle,
      the receptor involved in the serotoninergic response is a 5HT1-like subtype,
      possibly a 5HT1D. In this preparation, under our experimental conditions, there
      was no evidence for the presence of 5HT2 receptors. The induction of
      atherosclerosis did not induce significant changes in the serotoninergic response
      in these large coronary arteries, illustrating the marked heterogeneity between
      microvasculature and large arteries in the rabbit heart.

PMID- 8301548
TI  - Effects of E4080, a novel bradycardic agent with a coronary vasodilating
      property, on coronary and systemic hemodynamics in conscious dogs.
AB  - The effects of E4080 ((E)-N-[3-((N'-(2-(3,5-dimethoxyphenyl)-ethyl)-N'-
      methyl)amino)propyl]-4-(4-(1H-imidazol-1-yl)-phenyl)-3-butenamide dihydrochloride
      dihydrate), a novel bradycardic agent with a coronary vasodilating property, on
      coronary and systemic hemodynamics were compared with those of pinacidil and
      nifedipine in chronically instrumented conscious dogs. A pair of piezoelectric
      crystals and an electromagnetic flow probe were placed on the left circumflex
      coronary artery. Intravenous infusions of 30, 100 and 300 micrograms/kg/min of
      E4080 at 30-min intervals to six conscious dogs increased coronary blood flow and
      decreased total coronary resistance in a dose-dependent fashion, whereas coronary
      diameter tended to be increased. Although E4080 at a rate of 300
      micrograms/kg/min decreased maximally mean aortic pressure by 27 +/- 3% (n = 6, P
      < .05 vs. base-line value), there was no significant change in the maximal rate
      of rise in left ventricular pressure or heart rate. Both pinacidil (3, 10 and 30
      micrograms/kg/min) and nifedipine (1, 3 and 10 micrograms/kg/min) also tended to
      increase coronary diameter, and caused an increase in coronary blood flow and
      decreases in mean aortic pressure and total coronary resistance. In contrast to
      E4080, however, these changes caused by pinacidil and nifedipine were accompanied
      by a marked increase in heart rate. All of the drugs tested produced a
      significant and dose-dependent increase in plasma noradrenaline level. It is
      concluded that E4080 produces coronary and peripheral vasodilation, without
      inducing a reflex tachycardia despite sympathetic neural activation. These
      results suggest that E4080 exerts actions on the cardiovascular system which may
      be useful in the treatment of angina pectoris.

PMID- 8301549
TI  - Beta adrenergic modulation of formyl-methionine-leucine-phenylalanine-stimulated
      secretion of eosinophil peroxidase and leukotriene C4.
AB  - The inhibitory effect of beta-2 adrenergic receptor stimulation on leukotriene C4
      (LTC4) secretion and eosinophil peroxidase (EPO) release caused by exogenous
      activation with 10(-8) to 10(-6) M formyl-met-leu-phe (fMLP) + 5 micrograms/ml of
      cytochalasin B (Cyto B) in purified human peripheral blood eosinophils was
      studied. Cells from normal subjects were isolated by negative immunoselection and
      remained > or = 98% viable as determined by trypan blue exclusion. Duplicate
      aliquots of eosinophils (10(5) cells/intervention) were activated with 1) fMLP +
      Cyto B alone, 2) fMLP + Cyto B after pretreatment with 10(-8) M albuterol, 3) 10(
      8) M albuterol + fMLP + Cyto B after pretreatment with 10(-8) M propranolol or 4)
      vehicle control. After incubation, the supernatants were tested for concentration
      of LTC4 and EPO. Concentration-related release of EPO was demonstrated for 10(-8)
      M fMLP + 5 micrograms/ml of Cyto B to 10(-6) M fMLP + 5 micrograms/ml of Cyto B,
      and the greatest concentration of fMLP was used in all subsequent studies. FMLP +
      Cyto B caused substantial LTC4 secretion in eosinophils (300 +/- 83.0 pg/ml) as
      compared to sham-activated eosinophils (3.3 +/- 1.9 pg/ml; P < .02). Similarly,
      maximum EPO release increased from 277 +/- 17.8 to 3956 +/- 1230 ng/10(6) cells
      (P < .02) after activation with fMLP + Cyto B. Treatment with albuterol decreased
      markedly both LTC4 secretion to 144 +/- 54.0 pg/ml (P < .05 vs. fMLP + Cyto B
      activated eosinophils) and EPO release to 1993 +/- 368 ng/10(6) cells (P < .05
      vs. fMLP + Cyto B-activated eosinophils).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301550
TI  - Blood-brain barrier transport and brain metabolism of adenosine and adenosine
      analogs.
AB  - Adenosine transport through the brain capillary endothelial wall, which makes up
      the blood-brain barrier (BBB) in vivo, is mediated by a saturable transport
      system that has not been characterized extensively. Moreover, the inability of
      adenosine to augment cerebral blood flow in most species after intracarotid
      adenosine administration suggests the presence of an enzymatic BBB to circulating
      adenosine. Therefore, the present studies investigate the Michaelis-Menten
      kinetics of BBB adenosine transport and the rate of cerebral metabolism of
      circulating adenosine after internal carotid artery perfusion in anesthetized
      rats. The studies also assess the ability of various adenosine analogues to
      inhibit [3H]adenosine transport at the BBB in vivo. Initial rates of BBB
      transport of adenosine in vivo were observed for at least 15 sec of internal
      carotid artery perfusion. BBB adenosine transport was partially sodium-dependent
      and was saturable with the following kinetic parameters: Km = 1.1 +/- 0.2 microM;
      Vmax = 202 +/- 44 pmol/min/g; and KD = 34 +/- 6 microliters/min/g. BBB transport
      of [3H]adenosine was not inhibited by cyclohexyladenosine or S-(4-nitrobenzyl)-6
      thioinosine, but was inhibited by dipyridamole (Ki = 2.2 +/- 0.9 microM).
      Capillary depletion studies were performed, which demonstrated sequestration of
      [3H] radioactivity by the microvascular pellet after carotid arterial infusion of
      [3H]adenosine. Only 10 +/- 3% of cerebral [3H] radioactivity resided in the free
      adenosine pool after 15 sec of internal carotid artery perfusion of [3H]adenosine
      and rapid termination of brain metabolism with microwave irradiation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301551
TI  - Skin permeability and local tissue concentrations of nonsteroidal anti
      inflammatory drugs after topical application.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are being administered increasingly
      by transdermal drug delivery for the treatment of local muscle inflammation. The
      human epidermal permeabilities of different NSAIDs (salicylic acid, diethylamine
      salicylate, indomethacin, naproxen, diclofenac and piroxicam) from aqueous
      solutions is dependent on the drug's lipophilicity. A parabolic relationship was
      observed when the logarithms of NSAID permeability coefficients were plotted
      against the logarithms of NSAID octanol-water partition coefficients (log P), the
      optimum log P being around 3. The local tissue concentrations of these drugs
      after dermal application in aqueous solutions were then determined in a rat
      model. The extent of local, as distinct from systemic delivery, for each NSAID
      was assessed by comparing the tissue concentrations obtained below a treated site
      to those in contralateral tissues. Local direct penetration was evident for all
      NSAIDs up to a depth of about 3 to 4 mm below the applied site, with distribution
      to deeper tissues being mainly through the systemic blood supply. A comparison of
      the predicted tissue concentrations of each NSAID after its application to human
      epidermis was then made by a convolution of the epidermal and underlying tissue
      concentration-time profiles. The estimated tissue concentrations after epidermal
      application of NSAIDs could be related to their maximal fluxes across epidermis
      from an applied vehicle.

PMID- 8301552
TI  - Nonlinear pharmacokinetics of recombinant human macrophage colony-stimulating
      factor (M-CSF) in rats.
AB  - The pharmacokinetics and mechanisms of elimination of recombinant human
      macrophage-colony stimulating factor (M-CSF) were investigated in rats.
      Intravenous injections of 0.1, 1 or 10 mg/kg M-CSF were administered and plasma
      samples were measured for M-CSF by bioassay. Systemic clearance decreased and the
      shape of the concentration-time curve changed with increasing dose, indicating
      nonlinear pharmacokinetics. At 10 mg/kg, two half-lives were initially observed,
      but after about 20 hr the plasma M-CSF suddenly declined with a steep slope. The
      rapidly declining phase suggested a saturable clearance mechanism that was
      prominent at low plasma concentrations of M-CSF (below 300 ng/ml) and obscured at
      high plasma concentrations of M-CSF. The rapid decline of plasma M-CSF occurred
      at earlier times with multiple daily injections of M-CSF, indicating induction of
      the saturable clearance mechanism. The rapidly declining phase was inhibited by
      carrageenan, indicating that saturable clearance might be due to metabolism of M
      CSF by macrophages. With ligation of either the renal pedicles or ureters, the
      apparent half-lives of M-CSF increased by a factor of 2- to 3-fold, while the
      occurrence of the rapidly declining phase was delayed, but not eliminated.
      Overall, the results are well described by a two-compartment, first-order
      elimination model with a parallel Michaelis-Menten elimination pathway. First
      order elimination is largely performed by the kidneys and the saturable Michaelis
      Menten elimination pathway appears to be mediated by cells of the monocyte
      macrophage lineage.

PMID- 8301553
TI  - Correlation between leukotriene D4-induced contraction and cytosolic calcium
      elevation: a quantitative and simultaneous evaluation in smooth muscle.
AB  - The role of Ca++ as an intracellular messenger in leukotriene (LT)D4-induced
      muscle contraction was investigated by measuring force development and elevation
      in cytosolic Ca++ concentration simultaneously in strips of guinea pig ileal
      longitudinal muscle loaded with the fluorescent calcium indicator Fura 2. Upon
      addition of LTD4, a simultaneous increase in tension and cytosolic calcium
      concentration, [Ca++]i, was observed. Cumulative applications of LTD4 induced
      concentration-dependent increases in both muscle tension and [Ca++]i, being the
      half-maximal effect reached at approximately 6 to 9 nM. A statistically
      significant positive correlation (r = 0.993, P < .001) exists between the two
      parameters examined. Removal of calcium in the bathing solution, accompanied by
      addition of 7.5 mM EGTA, completely prevented any increase in either calcium
      levels or force development, thus indicating a role for Ca++ influx, rather than
      a release from intracellular stores. All of the LTD4 antagonists tested were able
      to counteract the effect of the leukotriene on both [Ca++]i and tension increase.
      However, although LY171883 shifted both of the LTD4 curves to the right in a
      parallel fashion, FPL 55712 and ICI 198,615 behaved as non-competitive
      antagonists in reversing the effect of LTD4 on [Ca++]i and tension. Thus, these
      results strongly suggest that changes in muscle tension induced by LTD4 are
      attributable to changes in cytosolic free Ca++ concentrations in guinea pig
      ileum.

PMID- 8301554
TI  - 5-Hydroxytryptamine2 receptor-mediated regulation of periventricular-hypophysial
      dopaminergic neuronal activity and the secretion of alpha-melanocyte-stimulating
      hormone.
AB  - The present study examined the effects of the 5-hydroxytryptaminergic (5HT)2/1c
      agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on periventricular
      hypophysial dopaminergic (DA) neuronal activity and the secretion of alpha
      melanocyte-stimulating hormone (alpha MSH). For comparison, the effects of DOI on
      tuberoinfundibular DA neuronal activity and the secretion of prolactin were also
      examined. Periventricular hypophysial and tuberoinfundibular DA neuronal
      activities were estimated by measuring the concentrations of 3,4
      dihydroxyphenylacetic acid (DOPAC) in the terminal regions of these neurons;
      i.e., in the intermediate lobe of the pituitary and median eminence,
      respectively. Acute administration of DOI produced dose- and time-related
      decreases in intermediate lobe DOPAC concentrations and corresponding increases
      in plasma alpha MSH concentrations. Pretreatment of animals with either the
      5HT2/1c antagonist ritanserin or the selective 5HT2 antagonist alpha-phenyl-1-(2
      phenylethyl)-4-piperidine methanol (MDL-11,939) blocked the DOI-induced decrease
      in intermediate lobe DOPAC concentrations and increase in plasma alpha MSH
      concentrations. Acute administration of DOI produced dose- and time-related
      increases in plasma prolactin concentrations but did not alter DOPAC
      concentrations in the median eminence. Furthermore, the DOI-induced increase in
      plasma prolactin concentrations was blocked by ritanserin, but not MDL-11,939
      pretreatment. Taken together, these data suggest that DOI inhibits
      periventricular hypophysial DA neuronal activity and increases the secretion of
      alpha MSH by activating 5HT2 receptors, whereas the DOI-induced prolactin
      secretion is independent of a decrease in tuberoinfundibular DA neuronal activity
      and is most likely mediated by 5HT2/1c receptor activation.

PMID- 8301555
TI  - Characterization of a dual inhibitor of angiotensin I-converting enzyme and
      neutral endopeptidase.
AB  - In the present study we characterize key activities of an agent designed to
      simultaneously inhibit angiotensin I-converting enzyme (ACE) and neutral
      endopeptidase (NEP). MDL 100,240 is a thioester prodrug of MDL 100,173, which is
      a potent competitive inhibitor of both ACE and NEP in vitro. MDL 100,240 was
      shown in an ex vivo study to inhibit both of these enzymes in rat kidney. When
      administered to anesthetized rats, MDL 100,240 enhanced the effect of infused ANP
      on blood pressure, diuresis and natriuresis and of infused bradykinin on blood
      pressure. Moreover, MDL 100,173 and MDL 100,240 inhibited the pressor response to
      angiotensin I. These results indicate that MDL 100,173 and its prodrug, MDL
      100,240, produced effects, in vivo, consistent with inhibition of both ACE and
      NEP.

PMID- 8301556
TI  - Class I antiarrhythmic drugs: allosteric inhibitors of [3H] batrachotoxinin
      binding to rat cardiac sodium channels.
AB  - This study assessed whether class I antiarrhythmic drugs allosterically inhibit
      [3H]batrachotoxinin A 20-alpha-benzoate ([3H]BTXB) binding to sodium channels on
      freshly isolated rat cardiac myocytes. All class I drugs tested inhibited
      equilibrium [3H]BTXB binding in a concentration-dependent manner. Scatchard
      analysis showed that disopyramide, flecainide, transcainide, lidocaine and
      amiodarone reduced [3H]BTXB maximum binding (Bmax) whereas procainamide,
      mexiletine, quinidine, quinine, tocainide, propafenone, encainide and O
      demethylencainide increased [3H]BTXB KD but had little effect on Bmax. Kinetic
      [3H]BTXB binding assays were used to assess the mechanism by which class I drugs
      inhibit [3H]BTXB binding. Drugs that increase the unidirectional dissociation
      rate constant (k-1) of [3H]BTXB probably bind to sodium channels to which
      [3H]BTXB is already bound. Although all class I drugs increased the k-1 of
      [3H]BTXB, they did so weakly and at concentrations above the IC50 values of the
      drugs. Thus, drug binding to [3H]BTXB-bound channels does not appear to be the
      predominant mechanism underlying their ability to inhibit [3H]BTXB binding.
      Conversely, drugs which allosterically decrease the unidirectional association
      rate constant (K+1) of [3H]BTXB probably bind to channels to which [3H]BTXB is
      not already bound. All class I drugs decreased the k+1 of [3H]BTXB, indicating
      drug binding to [3H]BTXB-free channels. The estimated affinities of drugs for
      [3H]BTXB-free channels correlated closely with the IC50 values of these drugs (r
      = 0.94, P < .001), suggesting that this effect is a common and major determinant
      in their ability to inhibit [3H]BTXB binding. The results are discussed in light
      of electrophysiologic theories of class I antiarrhythmic drug action.

PMID- 8301557
TI  - Human parathyroid hormone fragment(1-34) and human [Ala25,26,27]parathyroid
      hormone fragment(1-34): their vascular and intracellular calcium regulating
      action in vascular smooth muscle cells.
AB  - Human parathyroid hormone fragment, hPTH(1-34) and its analog,
      [Ala25,26,27]hPTH(1-34), were tested for their effects on rat blood pressure,
      tension generation in rat tail artery helical strips and intracellular calcium
      concentration ([Ca++]i) in smooth muscle cells of the rat tail artery. Amino
      acids at positions 25, 26 and 27 are reported to be responsible for the vascular
      action of the PTH molecule. The present studies demonstrate that hPTH(1-34), but
      not [Ala25,26,27]hPTH(1-34), produces a dose-dependent hypotensive effect in
      Sprague-Dawley (SD) rats and a dose-dependent relaxing effect on SD rat tail
      artery helical strips precontracted by norepinephrine, KCl or arginine
      vasopressin. Accordingly, hPTH(1-34), but not [Ala25,26,27]hPTH(1-34), inhibits
      the [Ca++]i increment induced by 15 mM KCl in cultured vascular smooth muscle
      cells (VSMC) from the SD rat tail artery after incubation with the peptide for 5
      to 10 min. In addition, both hPTH(1-34) and [Ala25,26,27]hPTH(1-34) cause an
      initial transient and immediate increase in [Ca++]i in VSMC which does not
      correlate with any demonstrable vascular action. We suggest that PTH can elicit
      an initial increase in [Ca++]i and a subsequent inhibition of stimulated [Ca++]i
      increase in VSMC. The initial [Ca++]i effect is not related to its vascular
      action, whereas the subsequent inhibitory effect correlates well with its
      hypotensive effect.

PMID- 8301558
TI  - Modulation of morphine tolerance by the competitive N-methyl-D-aspartate receptor
      antagonist LY274614: assessment of opioid receptor changes.
AB  - Recent reports have demonstrated that the coadministration of morphine with an N
      methyl-D-aspartate (NMDA) receptor antagonist can attenuate and/or reverse the
      development of morphine tolerance. In the present study we used an experimental
      tolerance paradigm using morphine pellets (75 mg) to produce an 1-fold shift in
      the morphine dose-response curve in rats. Coadministration of the competitive
      NMDA receptor antagonist LY274614 [(+-)-6-phosphonomethyl-decahydroisoquinolin-3
      carboxylic acid] via continuous s.c. infusion (24 mg/kg/24 hr) significantly
      attenuated the development of morphine tolerance. In addition, animals made
      tolerant to morphine and then infused with LY274614 (24 mg/kg/24 hr) regained
      their analgesic sensitivity to morphine more rapidly than morphine-tolerant
      animals given a saline infusion. To determine whether LY274614 treatment modifies
      the subsequent development of tolerance, LY274614 was administered to nontolerant
      animals for 1 week. One week after LY274614 treatment was discontinued the
      animals were challenged with morphine and then implanted with morphine pellets.
      Neither the expression of morphine analgesia nor the development of morphine
      tolerance differed when LY274614- and saline-treated animals were compared. The
      infusion of LY274614 for 7 days did not increase the affinity or density of mu,
      delta, kappa-1 or kappa-3 opioid receptors in rat brain homogenates as measured
      by ligand binding assays. Additionally, the IC50 values for LY274614 in mu-1, mu
      2, delta, kappa-1 or kappa-3 ligand binding assays were greater than 10 microM.
      Taken together these results demonstrate that the competitive NMDA receptor
      antagonist LY274614 can both attenuate and reverse the development of morphine
      tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301559
TI  - Species differences in the binding characteristics of [125I]IRL-1620, a potent
      agonist specific for endothelin-B receptors.
AB  - [125I]Tyr13-Suc-[Glu9,Ala11,15]-Endothelin-1 (8-21) ([125I]IRL-1620) displayed
      specific, saturable and high affinity binding to membranes prepared from rat and
      dog cerebellum, rat and human lung and cloned human endothelin-B (ETB) receptors.
      The apparent dissociation constant (Kd) for rat cerebellum, dog cerebellum, rat
      lung, human lung and human ETB clone were 69.1, 34.8, 128, 71.9, and 115 pM,
      respectively. The maximum binding (Bmax) to these membranes were 3.2, 0.71, 1.67,
      1.85 and 62.3 pmol/mg of protein for rat cerebellum, dog cerebellum, rat lung,
      human lung and human ETB clone, respectively. Unlabeled endothelin-1 (ET-1), ET-3
      and sarafotoxin 6c (S6c) displaced [125I]IRL-1620 binding to these membranes with
      similar affinity (IC50 = 0.1-2.5 nM), whereas cyclo(D-Trp,D-Asp,L-Pro,D-Val,L
      Leu), a selective antagonist for ETA receptors, had no effect on [125I]IRL-1620
      binding up to 1 microM. Time course experiments of association and dissociation
      indicated that [125]IRL-1620 binding to dog and human tissues and human ETB clone
      was rapid and reversible, whereas in rat tissues, the binding was rapid but
      irreversible, suggesting that this might be due to species difference. [125I]ET-1
      binding was irreversible in all the tissues tested. No binding of [125I]IRL-1620
      was detectable in rat vascular smooth muscle cells or cloned human ETA receptors.
      These data indicate that [125I]IRL-1620 is highly selective for ETB receptors and
      the reversible binding characteristics of this ligand appears to be species
      dependent.

PMID- 8301560
TI  - Mechanism of cyclic AMP-induced hyperpolarization in canine colon.
AB  - The mechanism of forskolin (FSK)-induced hyperpolarization was investigated in
      strips of canine colonic circular muscle. FSK responses were compared to those of
      the K+ channel opener lemakalim (LEM). Both FSK (10 microM) and LEM (10 microM)
      hyperpolarized cells near the myenteric border by 10 to 20 mV. Responses to both
      agents were abolished by 35 mM external K+, indicating a probable mediation by K+
      channels. FSK increased the open probability of Ca(++)-activated K+ channels in
      isolated colonic myocytes. However, in muscle strips charybdotoxin (100 nM) and
      tetraethylammonium (10 mM) failed to reduce FSK- and LEM-induced
      hyperpolarizations whereas tetrapentylammonium (50 microM) and 4-aminopyridine
      (10 mM) blocked both responses. Phencyclidine (100 microM), Ba++ (1 mM) and the
      antagonist of ATP-sensitive K+ currents glybenclamide (10 microM) blocked LEM-
      but not FSK-induced hyperpolarizations. Delayed rectifier current in isolated
      myocytes was activated near -20 mV and was blocked by (order of potency):
      nifedipine > tetrapentylammonium > phencyclidine > 4-aminopyridine >
      tetraethylammonium. Charybdotoxin (100 nM), Ba++ (1 mM) and glybenclamide (10
      microM) were without effect. Ca(++)-activated K+ current was activated near +30
      mV and was blocked by: charybdotoxin > tetraethylammonium > tetrapentylammonium
      >> phencyclidine = 4-amino-pyridine. These data suggest that LEM induces membrane
      hyperpolarization by activation of a K+ current with a pharmacology similar to
      ATP-sensitive K+ current whereas cyclic AMP-induced hyperpolarization appears to
      involve activation of a current other than delayed rectifier current, Ca(++)
      activated K+ current or ATP-sensitive K+ current.

PMID- 8301561
TI  - Identification of simple substituted phenols with thyromimetic activity: cardiac
      effects of 3,5-diiodo-4-hydroxyphenylpropionic acid.
AB  - To define the minimal structural requirements for cardiac activity of thyroid
      hormone analogs, a series of substituted phenols were screened for their ability
      to bind bacterially expressed thyroid hormone receptors. Compounds with binding
      activity then were tested for their ability to induce expression of alpha-myosin
      heavy chain mRNA in primary cultures of fetal rat cardiomyocytes, a sensitive
      marker for potential inotropic activity. 3,5-Diiodo-4-hydroxyphenylpropionic acid
      (DIHPA) was found to bind specifically to bacterially expressed alpha-1 and beta
      1 thyroid hormone receptors (Kaff approximately 1 to 2 x 10(5) M-1) and to induce
      alpha-myosin heavy chain (EC50 approximately 5 x 10(-7)). To assess the effects
      of DIHPA on cardiac performance in vivo, hemodynamic measurements were made in
      three groups of hypothyroid rats treated for 5 days with s.c. doses of DIHPA (15
      mg/100 g), L-thyroxine (T4, 1.5 micrograms/100 g) or saline. Compared to
      controls, DIHPA and T4 produced increases in heart rate, left ventricular
      +dP/dtmax, -dP/dtmax, and isovolumic relaxation. In isometric papillary muscles
      preparations, DIHPA and T4 shortened time-to-peak tension and time-from-peak
      tension to 50% decline as compared with saline-treated controls. Muscles from
      both drug-treatment groups showed similar responses to graded doses of
      isoproterenol (10(-8) to 10(-3) M) and to variations in Ca++ concentration of the
      muscle bath (0.3125 to 3.75 x 10(-3) M). Thus, DIHPA is a novel thyromimetic
      compound with effects on myocardial function similar to those observed with T4.

PMID- 8301562
TI  - Losartan improves the natriuretic response to ANF in rats with high-output heart
      failure.
AB  - During severe congestive heart failure (CHF), a number of sodium-retaining and
      vasoconstricting mechanisms are activated, including the renin-angiotensin
      aldosterone system. In CHF, the renal effects of atrial natriuretic factor (ANF)
      are attenuated. The interaction of these endocrine factors is a major determinant
      of the clinical course of CHF. This study was designed to evaluate the role of
      the renin-angiotensin-aldosterone system in the development of avid sodium
      retention in CHF, induced in rats by creation of an aorto-caval fistula. Rats
      with aorto-caval fistula either compensate and maintain a normal sodium balance
      (UNaV > 1400 microEq/day) or decompensate and develop severe sodium retention
      (UNaV < 200 microEq/day), which leads to severe CHF. Chronic treatment with
      losartan, an angiotensin II receptor blocker, 10 mg/day, resulted in dramatic
      natriuresis (UNaV > 1000 microEQ/day) in decompensated rats, but not in
      compensated rats or controls. ANF infusion (50 micrograms/kg/hr) increased
      fractional sodium excretion 46-fold in compensated rats, but only 18-fold in
      decompensated rats. A similar pattern of responsiveness to ANF was observed in
      urinary cyclic GMP excretion. Chronic losartan treatment restored the natriuretic
      and urinary cyclic GMP excretion responses of decompensated rats to ANF. The
      improvement in the natriuretic response after losartan treatment was associated
      with a suppression of the previously elevated plasma aldosterone. These results
      demonstrate the pivotal role of angiotensin II in the development of sodium
      retention and of the blunted renal response to ANF in CHF, and indicate why
      losartan is useful therapy for cardiac edema.

PMID- 8301563
TI  - Supersensitization of the oral response to SKF 38393 in neonatal 6
      hydroxydopamine-lesioned rats is eliminated by neonatal 5,7-dihydroxytryptamine
      treatment.
AB  - 5-Hydroxytryptamine (5-HT) 5-HT2c receptors mediate the enhanced oral activity
      response to the dopamine (DA) D1 agonist, (+/-)-1-phenyl-2,3,4,5-tetrahydro-1H-3
      benzazepine-7,8-diol (SKF 38393) in neonatal 6-hydroxydopamine (6-OHDA)-lesioned
      rats. To study the possible involvement of 5-HT fibers on this process, the
      effect of the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) was determined.
      Rats were treated at 3 days after birth with desipramine (20 mg/kg i.p., base) 1
      hr before intracerebroventricular vehicle, 6-OHDA (134 micrograms, base) and/or
      5,7-DHT (50 micrograms, base). Oral activity was observed at 7 weeks and later.
      In neonatal 6-OHDA-lesioned rats oral activity dose-effect responses were
      increased by SKF 38393, 1-(3-chlorophenyl)-piperazine (m-CPP) and pilocarpine
      respective DA D1, 5-HT2c and muscarinic receptor agonists. Rats treated
      neonatally with 5,7-DHT had agonist-induced responses resembling that of the
      saline control group. However, in rats treated neonatally with both 5,7-DHT and 6
      OHDA, oral activity responses were reduced at nearly all doses of SKF 38393 and
      pilocarpine vs. that of the 6-OHDA group. The response of the 5,7-DHT + 6-OHDA
      group to m-CPP was reduced at only the 1.0 mg/kg dose. Of a variety of
      stereotyped behaviors that were observed in separate test sessions, m-CPP-induced
      grooming activity was less in the 5,7-DHT + 6-OHDA group vs. the 6-OHDA
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301564
TI  - Modulation of superoxide generation in in vivo lipopolysaccharide-primed Kupffer
      cells by staurosporine, okadaic acid, manoalide, arachidonic acid, genistein and
      sodium orthovanadate.
AB  - Continuous infusion of a nonlethal dose of Escherichia coli lipopolysaccharide
      (LPS) into rats induced extravasation of mononuclear phagocytes into the liver
      and the priming of Kupffer cells for in vitro phorbol myristate acetate (PMA)
      stimulated superoxide anion (O2-) release. The purpose of this investigation was
      to determine the role of protein kinase C (PKC), protein serine-threonine
      phosphatase(s) 1 and 2a, protein tyrosine kinase(s) and phosphatase(s),
      phospholipase A2 (PLA2), arachidonic acid (AA) and its cyclooxygenase (CO) and 5
      lipoxygenase (5-LO) metabolites in the modulation of PMA-stimulated O2-generation
      in in vivo LPS-primed rat Kupffer cells. The following inhibitors blocked PMA
      stimulated O2- generation in the absence (-AA) or presence of AA (+AA) (50
      microM): 1) staurosporine, a putative PKC inhibitor (150 nM, 95% inhibition
      without AA, 88% inhibition with AA); 2) okadaic acid, a protein serine-threonine
      phosphatase inhibitor (2 microM, 65% inhibition with or without AA); 3) the
      marine PLA2 inhibitor manoalide (1 microM, 97.5% inhibition without AA, 75% with
      AA). In addition, it was observed that exogenously added AA enhanced PMA
      stimulated O2- generation in a time- and dose-dependent manner (5-50 microM) and
      partially reversed the inhibitory effect of manoalide. The following inhibitors
      did not block PMA-stimulated O2- generation in the absence or presence of AA: 1)
      indomethacin, a CO inhibitor (1-100 microM) and WY-50,295M tromethamine, a novel
      5-LO inhibitor (1-100 microM); 2) genistein, a protein tyrosine kinase inhibitor
      (1-100 microM); and 3) sodium orthovanadate (1-300 microM), a protein tyrosine
      phosphatase inhibitor. It was concluded that, in in vivo LPS-primed Kupffer
      cells, PMA-stimulated O2- generation is modulated by PKC, protein serine
      threonine phosphatase(s), PLA2 and AA but not by protein tyrosine kinase(s) and
      phosphatase(s) and CO and 5-LO products. These findings could have implications
      on the design of novel therapeutic approaches for the modulation of enhanced O2-
      release by Kupffer cells in endotoxemia.

PMID- 8301565
TI  - Enhancement of noradrenaline release from rat frontal cortex by thyrotropin
      releasing hormone and its analog, (3R,6R)-6-methyl-5-oxo-3
      thiomorpholinylcarbonyl-L-histidyl-L-prolinami de, as studied by intracerebral
      microdialysis.
AB  - The effects of thyrotropin-releasing hormone (TRH) and NS-3 [CG-3703: (3R,6R)-6
      methyl-5-oxo-3-thiomorpholinylcarbonyl-L-histidyl-L- prolinamide], a
      metabolically stable analog of TRH, on the extracellular concentration of
      noradrenaline (NA) in the frontal cortex of urethane anesthetized rats were
      examined by using intracerebral microdialysis coupled with high-performance
      liquid chromatography with electrochemical detection. NS-3 (0.1 and 0.3 mg/kg
      i.v.) produced a significant increase in NA release. This effect reached to its
      peak 20 to 40 min (174% of basal level) after NS-3 (0.3 mg/kg) injection and
      exhibited a duration of 80 min. TRH (10 mg/kg i.v.) also significantly increased
      NA concentrations to the same extent as that produced by 0.3 mg/kg of NS-3,
      although the effect of TRH was transient. Blockade of NA reuptake by perfusion
      with desipramine (10(-7) M) caused a gradual increase in extracellular NA
      concentration. NS-3 at 0.3 mg/kg (i.v.) produced a significant elevation of NA
      concentrations after desipramine perfusion. When NS-3 (10(-6) and 10(-5) M) was
      perfused to the frontal cortex through the dialysis probe for 1 hr, no
      significant change in cortical NA concentration was observed. In contrast,
      perfusion of NS-3 (10(-5) M) through the dialysis probe implanted into the locus
      ceruleus induced a significant increase in the cortical NA release. These results
      suggest that NS-3 is far more active than TRH in facilitating cortical NA release
      and that the locus ceruleus is one of sites of action of this drug.

PMID- 8301566
TI  - Relaxant responses of rabbit aorta: influence of cytochrome P450 inhibitors.
AB  - Based on the use of inhibitors, cytochrome P450 has been implicated in
      endothelium-dependent relaxant responses via metabolism of arachidonic acid (AA).
      However, the contribution of cytochrome P450 and its AA metabolites to the
      regulation of vascular tone has not been established due, in part, to questions
      of specificity of cytochrome P450 inhibitors which have not been extensively
      characterized in terms of their vascular effects. Consequently, we addressed the
      effects of several inhibitors on vasorelaxant responses of phenylephrine
      contracted, rabbit, aortic rings to agents that utilize different transduction
      mechanisms to determine any actions unrelated to inhibition of cytochrome P450
      and/or AA metabolism. Octadecynoic acid (2.5 and 5 microM), a mechanism-based
      inhibitor of cytochrome P450 metabolism of fatty acids, and eicosatetrayenoic
      acid (10 and 20 microM), an inhibitor of AA metabolism, were without effect on
      vasorelaxant responses to acetylcholine, sodium nitroprusside, isoproterenol and
      diazoxide. 7-Ethoxyresorufin (2-10 microM), a substrate for cytochrome P450, and
      clotrimazole (2.5-10 microM) which binds to the heme moiety of the enzyme,
      concentration-dependently reduced responses to acetylcholine but not the other
      agonists indicating an effect on nitric oxide synthesis although neither affected
      the conversion of L-arginine to L-citrulline by endothelial cells. SKF 525A (50
      200 microM), the prototypical inhibitor of cytochrome P450, which is metabolized
      to an inhibitory intermediate, also reduced responses to acetylcholine and, in
      addition, impaired the vasorelaxant activities of isoproterenol and diazoxide.

PMID- 8301567
TI  - Differential effects of histamine on the activity of hypothalamic dopaminergic
      neurons in the rat.
AB  - The effect of intracerebroventricular administration of histamine on hypothalamic
      dopaminergic neuronal activity was estimated in male rats by measuring
      concentrations of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid
      (DOPAC) in brain regions containing terminals or perikarya of these neurons.
      Three distinct, regionally specific neurochemical responses were apparent. In the
      median eminence and intermediate lobe of the pituitary, histamine affected
      neither DOPAC nor dopamine concentrations, suggesting no effect on
      tuberoinfundibular or periventricular-hypophysial dopaminergic neuronal activity.
      In the medial zona incerta and in the dorsomedial, rostral periventricular and
      medial preoptic hypothalamic nuclei, histamine effected a dose- and time-related
      increase in both DOPAC and dopamine concentrations; these effects were blocked by
      destruction of noradrenergic neurons projecting to these regions, suggesting that
      these changes are attributable to noradrenergic neuronal activation, and that
      histamine does not affect the activity of incertohypothalamic or periventricular
      preoptic dopaminergic neurons located in these brain regions. In the
      suprachiasmatic, caudal periventricular and paraventricular hypothalamic nuclei,
      histamine effected a dose- and time-related increase in DOPAC, but not dopamine,
      concentrations; these effects were blocked by the H1 antagonist mepyramine, but
      not the H2 antagonist zolantidine. Destruction of noradrenergic neurons
      projecting to these regions did not prevent the histamine-induced increases in
      DOPAC concentrations. These data indicate that histamine increases the activity
      of dopaminergic neurons projecting to the suprachiasmatic, caudal periventricular
      and paraventricular nuclei via an action at H1 receptors. Overall, these results
      reveal that i.c.v. administration of histamine differentially affects the
      activity of the various dopaminergic neuronal systems of the rat hypothalamus.

PMID- 8301569
TI  - Albumin decreases myocardial permeability of unbound quinidine in perfused rat
      heart.
AB  - With the single-pass, isolated, perfused rat heart preparation, we examined the
      effect of different perfusate albumin concentrations on the capillary
      permeability and pharmacodynamic effects of quinidine. Nine hearts were perfused
      for five consecutive 35-min phases with buffer containing quinidine and albumin
      concentrations of 0%, 0.1%, 1%, 6% and 0%, in that order, with a 55-min washout
      between each phase. Compared with 0% albumin perfusate, the equilibrium rate of
      quinidine perfusate output concentration (Cout) was slower with 0.1% albumin but
      faster with 1% and 6% albumin. Quinidine Cout, unbound fraction (fu) and
      perfusion flow rate (Q) for each phase of each experiment were fitted by a
      modified Kety-Renkin-Crone equation. Estimates of the capillary permeability
      surface product (PS) for the two 0% albumin phases (14.4 +/- 5.6 and 12.3 +/- 4.4
      ml/min) were significantly higher than those for the three albumin phases (5.3 +/
      1.0, 6.7 +/- 1.2 and 7.4 +/- 2.2 ml/min, respectively; P < .05). There was a
      direct, linear relationship between lengthening of the QT interval of the ECG and
      total and unbound quinidine concentrations, but the relationship for unbound
      concentration was independent of fu, showing that the pharmacodynamic effect was
      mediated by unbound concentration. In four additional experiments with antipyrine
      instead of quinidine, PS for the two 0% albumin phases (24.7 +/- 6.5 and 23.2 +/-
      2.4 ml/min) was not significantly different than that for the three albumin
      phases (25.5 +/- 6.1, 22.5 +/- 2.9 and 22.9 +/- 3.6 ml/min, respectively).
      Albumin had no effect on the volume of distribution referenced to unbound drug
      for either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301568
TI  - Chronic cocaine administration is associated with behavioral sensitization and
      time-dependent changes in striatal dopamine transporter binding.
AB  - Chronic cocaine administration has been associated with sensitization (an
      increase in drug effect) rather than the tolerance observed with many
      psychotropic compounds. Because cocaine acts at the presynaptic dopamine
      transporter, we evaluated sensitization and striatal dopamine transporter binding
      in vivo in several mouse strains. All strains of mice evaluated showed increased
      activity after cocaine compared with after saline injections. BALB/cByJ, DBA/2J,
      B6AF1/J and C57BL6/J mice exhibited sensitization when assayed 72 hr after five
      daily injections of cocaine at 20 and 40 mg/kg/day, whereas B6AF1/J mice showed
      sensitization at 20 but not at 40 mg/kg/day. CD-1 mice did not exhibit
      sensitization at either dose. Striatal dopamine transporter binding in vivo was
      increased in DBA/2J and B6AF1/J mice when determined 72 hr after five injections
      of 40 mg/kg/day cocaine. In contrast, a continuous infusion of cocaine at the
      same dose and duration did not produce sensitization or binding changes in DBA/2J
      mice. The time course of transporter binding alterations after intermittent
      cocaine exposure indicated no change at 1 day, increased binding at 3 days, a
      return to control levels at 7 days and decreased binding at 14 days. These data
      indicate that both sensitization and alterations in dopamine transporter binding
      occur after chronic cocaine injection but that these changes are unlikely to be
      directly related.

PMID- 8301570
TI  - Nitric oxide and castor oil-induced diarrhea.
AB  - The effect of NG-nitro-L-arginine methyl ester (L-NAME) on castor oil-induced
      diarrhea was studied in control rats and those treated with isosorbide dinitrate
      or isosorbide-5-mononitrate. Castor oil (2 ml) produced diarrhea that lasted at
      least 8 h. Pretreatment of the rats with L-NAME (1-25 mg/kg i.p.) 15 min before
      castor oil did not block the castor oil-induced diarrhea beyond 3 h after
      challenge but delayed its appearance (P < .05-.001). However, diarrhea was
      inhibited (P < .01-.001) during the entire 8 h if rats were treated twice with L
      NAME (25 mg/kg) (15 min before and 3 h after castor oil). These findings suggest
      that L-NAME, once administered, loses its activity 3 h after its administration.
      The nitric oxide synthase substrate, L-arginine (150-600 mg/kg), reversed (P <
      .05-.01) the inhibitory effect of L-NAME on diarrhea induced by castor oil. This
      effect is enantiomer-specific because D-arginine (900 mg/kg) was without an
      effect. These results suggest that castor oil-induced diarrhea in rats involves
      the L-arginine nitric oxide pathway. This is further supported by the effect of
      isosorbide dinitrate (0.6-120 mg/kg) and isosorbide-5-mononitrate (0.6-120
      mg/kg). When administered to castor oil-treated rats, these two nitric oxide
      generating agents prevented in a dose-dependent fashion (P < .01-.001) the
      inhibitory effect of L-NAME (25 mg/kg).

PMID- 8301571
TI  - Nicotine metabolic profile in man: comparison of cigarette smoking and
      transdermal nicotine.
AB  - The objectives of this study were to 1) quantitatively assess human exposure to
      various metabolites of nicotine, 2) examine the influence of inhalation vs.
      transdermal administration on the patterns of nicotine metabolism, and 3) assess
      the extent of recovery of nicotine as various metabolites in people whose
      systemic intake of nicotine has been measured. Twelve smokers were studied while
      smoking cigarettes and while receiving transdermal nicotine. Urinary excretion of
      nicotine and eight of its metabolites was measured under steady state conditions.
      The systemic intake of nicotine in these subjects was determined using plasma
      concentrations and intravenous clearance data, so the percentage of their daily
      dose of nicotine excreted as various metabolites could be computed. The major
      findings of the study are as follows: 1) a high percentage (averaging 88%) of a
      systemic dose of nicotine can be accounted for by measurement of nicotine and its
      metabolites; 2) the pattern of metabolism is generally similar when nicotine is
      inhaled or absorbed transdermally; 3) while there is considerable interindividual
      variability in the pattern of metabolism, the pattern is consistent for an
      individual; and 4) within individuals, the extent of conjugation of nicotine and
      cotinine is highly correlated, but neither is correlated with the extent of
      conjugation of 3'-hydroxycotinine. This suggests that similar enzymes are
      involved in the conjugation of nicotine and cotinine, and that a different enzyme
      may be involved in the conjugation of 3'-hydroxycotinine.

PMID- 8301572
TI  - Differential antagonism of airway contractile responses to prostaglandin (PG)D2
      and 9 alpha, 11 beta-PGF2 by atropine, SK&F 88046 and SQ 29,548 in the guinea
      pig.
AB  - PGD2, the predominant prostanoid released from activated human lung mast cells,
      is metabolized to 9 alpha, 11 beta-PGF2 by an 11-ketoreductase. Both prostanoids
      contract mammalian airway smooth muscle. In the present study, aerosol
      administration of PGD2 or 9 alpha, 11 beta-PGF2 (five puffs of 10-50
      micrograms/ml) to anesthetized, spontaneously breathing guinea pigs produced
      significant increases in airway resistance and decreases in dynamic lung
      compliance. The changes in airway resistance and dynamic lung compliance induced
      by 50 micrograms/ml were reduced approximately 60% and 25%, respectively, by
      pretreatment with atropine (1 mg/kg, i.v., -10 min). Pretreatment with the TxA2
      receptor antagonist SK&F 88046 (N,N'-bis[7-(3-chlorobenzene aminosulfonyl)
      1,2,3,4- tetrahydroisoquinolyl]disulfonylimide) (5 mg/kg, i.v., -10 min), nearly
      abolished the changes in airway resistance and dynamic lung compliance that were
      elicited by both agonists. Pretreatment with a TxA2 synthase inhibitor, CGS 13080
      (10 mg/kg, i.v., -10 min), had no effect on PGD2- or 9 alpha, 11 beta-PGF2
      induced bronchoconstriction, suggesting that these prostanoids did not provoke
      the release of TxA2. In vitro, PGD2, 9 alpha, 11 beta-PGF2 and a TxA2 mimic, U
      44069, produced concentration-dependent contractions of the guinea pig isolated
      trachea with pD2s of 6.4, 6.0 and 7.2, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8301573
TI  - Effects of KC 399, a novel ATP-sensitive K+ channel opener, on electrical and
      mechanical responses in dog tracheal smooth muscle.
AB  - The effects were observed of a newly synthesized bronchodilator, KC 339 [N-(2
      cyanoethyl)-2,2-bis-fluoromethyl-6-nitro-2H-1-benzopyran-4- carbothioamide], on
      the electrical and mechanical properties of dog tracheal smooth muscle tissues
      and on accumulation of second messengers. KC 399 hyperpolarized the membrane in a
      concentration-dependent manner, the minimum concentration required to produce
      hyperpolarization being 1 nM and the maximum hyperpolarization occurring with 10
      nM. The hyperpolarization was still observed in low K+ solution (< 1.2 mM), but
      not in high K+ solution (> 20 nM). Similarly, KC 399 inhibited the contraction
      evoked by less than 30 mM K+, but not by higher concentrations of K+ (> 30 mM).
      KC 399 (10 nM) suppressed the depolarization and membrane potential oscillation
      induced by carbachol (< 300 nM). In muscle tissues precontracted with 100 nM
      carbachol, KC 399 caused a concentration-dependent relaxation. The IC50 value for
      KC 399 was 4.2 nM (pIC50: 8.38 +/- 0.09, n = 7) and the maximum inhibition
      induced by 100 nM KC 399 was 96.1 +/- 0.7% (n = 7). KC 399 inhibited more
      effectively the tonic response of the contraction than the initial phasic
      response induced by carbachol. The relaxation and hyperpolarization induced by KC
      399 were antagonized by glibenclamide and in part by charybdotoxin due to
      depolarization of the membrane. Carbachol increased the amount of d-myo-inositol
      1,4,5-trisphosphate (InsP3), the maximal value occurring 10 sec after
      application.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301574
TI  - In vivo and in vitro structure-activity studies with peptide and pseudopeptide
      neurotensin analogs suggest the existence of distinct central neurotensin
      receptor subtypes.
AB  - The present study was designed to compare, with respect to structure-activity
      relationships, the receptors that subserve the hypothermic and analgesic effects
      of neurotensin (NT) to the receptor that mediates the effects of NT in
      mesencephalic dopamine (DA) neurons, and to compare these receptors to the cloned
      adult rat brain NT receptor and to newborn mouse and rat brain NT receptors. The
      results show that NT receptors in homogenates from newborn mouse and rat brain
      and from COS 7 cells transfected with the cloned high-affinity NT receptor from
      the adult rat brain displayed virtually identical structure-activity
      relationships toward a series of 12 peptide and pseudopeptide NT analogs, as
      assessed by the ability of the compounds to inhibit the binding of [125I]NT
      binding in these systems. Furthermore, when eight of these analogs were tested
      for their ability to inhibit [125I]NT binding and to potentiate K(+)-evoked DA
      release in primary cultures of rat mesencephalic neurons, it was found that they
      all behaved as agonists with binding and biological potencies quite similar to
      those observed in the other binding assays. Finally and strikingly, when seven of
      these analogs with checked metabolic stability were tested in vivo for their
      hypothermic and analgesic (tail-flick test) effects after i.c.v. injection in the
      mouse, they exhibited relative potencies that were completely different from
      those obtained in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301575
TI  - Novel benzodioxopiperazines acting as antagonists at postsynaptic 5-HT1A
      receptors and as agonists at 5-HT1A autoreceptors: a comparative pharmacological
      characterization with proposed 5-HT1A antagonists.
AB  - The novel benzodioxopiperazines [4-(benzodioxan-5-yl)1-[2- (benzocyclobutane-1
      yl)ethyl]piperazine] (S 14489), [4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine)]
      (S 15535) and [4-(benzodioxan-5-yl)1-[2(indan-1-yl)ethyl]piperazine (S15931)
      competitively displaced the binding of [3H]-8-OH-DPAT at serotonin (5-HT)1A
      receptors with affinities (pKis) of 9.2, 8.8 and 8.9, respectively. These values
      compared favorably with those of the structurally related eltoprazine (8.0) and
      the proposed 5-HT1A antagonists NAN-190 (9.2), MDL 73005 EF (8.9), SDZ 216-525
      (8.8), BMY 7378 (8.7), (-)-tertatolol (8.1), (-)-alprenolol (7.7), WAY 100,135
      (7.5) and spiperone (6.9). The affinities of S 14489, S 15535 and S 15931 for
      other 5-HT receptor types (5-HT1B, 5-HT1C, 5-HT1D, 5-HT2 and 5-HT3) were about 50
      to 1000-fold lower. The spontaneous tail-flicks, flat-body posture and
      hypothermia mediated by an action of the 5-HT1A agonist 8-OH-DPAT at postsynaptic
      5-HT1A receptors were dose-dependently and completely antagonized by S 14489, S
      15535 and S15931 at doses of 0.63 to 10.0 and 2.5 to 40.0 mg/kg for s.c. and oral
      administration, respectively. They did not induce these responses alone, and in
      their presence, dose-response curves for 8-OH-DPAT were shifted in parallel to
      the right without loss of maximal effect. By contrast, eltoprazine, MDL 73005 EF,
      BMY 7378 and NAN-190 behaved as "partial" agonists and only incompletely
      antagonized the actions of 8-OH-DPAT in these tests. At 5-HT1A autoreceptors, S
      14489, S 15535 and S 15931 acted as agonists in inhibiting striatal 5
      hydroxytryptophan accumulation (0.16-2.5 mg/kg, s.c.) and in abolishing the
      electrical activity of the dorsal raphe nucleus (0.005-0.100 mg/kg, i.v.).
      Eltoprazine, BMY 7378, NAN-190 and MDL 73005 EF also behaved as agonists at these
      5-HT1A autoreceptors, whereas WAY 100,135, spiperone, (-)-tertatolol, (-)
      alprenolol and SDZ 216-525 inhibited neither accumulation nor firing. WAY 100,135
      and spiperone antagonized the inhibition of DRN firing induced by S 14489, S
      15535 and S 15931. The affinity of 15535 for dopamine D1 and D2 receptors, as
      well as for beta-, alpha 1- and alpha 2-adrenoceptors, was > 100-fold lower than
      its affinity for 5-HT1A receptors. Further, in vivo, at doses of 10.0 to 40.0
      mg/kg, s.c., it showed minimal activity in tests of dopamine D2 (and D1) receptor
      mediated activity. Similarly, in vivo, S 15535 was weakly active in a test of
      alpha 1-adrenoceptor-mediated activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8301576
TI  - Leukotrienes mediate antigen-induced airway hyper-reactivity in guinea pigs.
AB  - The involvement of leukotrienes (LTs) in antigen-induced airway hyper-reactivity
      (AHR) was characterized pharmacologically by using several 5-lipoxygenase (5-LO)
      inhibitors and LTD4 antagonists in guinea pigs. AHR was evidenced by consistent
      and significant increases in sensitivity to bronchoconstriction induced by i.v.
      methacholine in anesthetized and ventilated animals 24 hr after a single
      ovalbumin aerosol challenge, but maximum methacholine-induced bronchoconstriction
      did not increase. Animals were pretreated with maximum doses of WY-50,295
      tromethamine (WY-50,295), LY-171,883, MK-886 or zileuton, based upon inhibition
      of antigen-induced LT-dependent bronchoconstriction. WY-50,295, having a long
      duration of action, was the only compound that prevented AHR when given once
      before antigen challenge. However, LY-171,883 and MK-886 prevented AHR when a
      second dose was given 4 hr after challenge. Zileuton, having a short duration of
      action, failed to prevent AHR when given before and after challenge. The
      prevention of AHR did not result from functional antagonism (bronchodilation) by
      any compound. In bronchoalveolar lavage studies, neither WY-50,295 nor MK-886
      inhibited the influx of eosinophils into the airways 24 hr after antigen
      challenge. The results provide pharmacological evidence that LTs play an
      important role in the pathogenesis of antigen-induced AHR in guinea pigs.
      Furthermore, the effectiveness of 5-LO inhibitors and LTD4 antagonists in this
      model depends upon a long duration of drug action and appears to result from
      inhibition of a direct airway effect of LTs rather than inhibition of eosinophil
      influx into the airways.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301577
TI  - Pharmacological comparison of two corticotropin-releasing factor antagonists: in
      vivo and in vitro studies.
AB  - The present study compared the effects of two analogs of corticotropin-releasing
      factor (CRF), [D-Phe12,Nle21,38, C alpha MeLeu37]CRF12-41 (D-PheCRF12-41) and
      alpha helical CRF9-41, as antagonists of CRF in in vivo and in vitro assays. In
      halothane-anesthetized rats, intracerebroventricular (i.c.v.) administration of
      both analogs inhibited the activation of locus coeruleus (LC) neuronal discharge
      produced by CRF (3.0 micrograms, i.c.v.). LC activation by hypotensive stress
      elicited by intravenous (i.v.) infusion of nitroprusside was antagonized by the
      same doses of the CRF antagonists that were effective in antagonizing CRF,
      suggesting that the receptors involved in LC activation by CRF and by hypotensive
      stress are similar. However, D-PheCRF12-41 was approximately 100 times more
      potent than alpha helical CRF9-41 when administered i.c.v. The IC50 values for D
      PheCRF12-41 as an antagonist of CRF and of nitroprusside were 0.16 and 0.14
      microgram, i.c.v., respectively. The IC50 values for alpha helical CRF9-41 as an
      antagonist of CRF and of nitroprusside were 18 and 27 micrograms, i.c.v.,
      respectively. In contrast, D-PheCRF12-41 was only slightly more potent than alpha
      helical CRF9-41 in antagonizing CRF-stimulated cyclic AMP production in rat brain
      homogenates, with IC50s of 78 +/- 15 and 260 +/- 30 nM for D-PheCRF12-41 and
      alpha helical CRF9-41, respectively. Moreover, the antagonists had similar
      affinities for CRF binding sites in rat brain homogenates, with Kis of 15.5 +/- 4
      nM and 10.3 +/- 6 nM for D-PheCRF12-41 and alpha helical CRF9-41,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301578
TI  - Effect of an orally active renin inhibitor Cl-992 on blood pressure in
      normotensive and hypertensive monkeys.
AB  - Cl-992, a novel potent inhibitor of primate renin, was tested for blood pressure
      lowering efficacy in sodium-restricted, furosemide-treated conscious normotensive
      cynomolgus monkeys and conscious renal hypertensive monkeys. The hypertensive
      monkey model provided an opportunity to determine the response to a renin
      inhibitor in a pathological nonhuman primate model of hypertension without
      concurrent diuretic treatment or dietary sodium restriction and on repeated oral
      administration. Cl-992 has IC50 values of 0.58 +/- 0.06 (n = 4) and 0.36 +/- 0.03
      nM (n = 8) against human and monkey renin, respectively. In normotensive monkeys,
      oral Cl-992 at doses of 3, 10 and 30 mg/kg reduced mean arterial blood pressure
      (MABP) by 8 +/- 2, 15 +/- 7 and 29 +/- 7 mm Hg (n = 5 animals per dose level, P <
      .05), respectively (base line, 103 +/- 3 mm Hg). Intravenous Cl-992 (0.0001 to
      0.1 mg/kg) also caused dose-dependent decreases in MABP and a maximum reduction
      of 23 +/- 4 mm Hg. The decrease in MABP after Cl-992 was paralleled by an
      inhibition of plasma renin activity (PRA) and a reduction in immunoreactive
      angiotensin II. In renal hypertensive monkeys, oral Cl-992 at doses of 3, 10 and
      30 mg/kg reduced MABP by 6 +/- 2, 18 +/- 6 and 37 +/- 8 mm Hg (n = 3 or 4, P <
      .05), respectively (base line, 134 +/- 4 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301579
TI  - MPP(+)-like neurotoxicity of a pyridinium metabolite derived from haloperidol: in
      vivo microdialysis and in vitro mitochondrial studies.
AB  - Intracerebral (intrastriatal, intranigral and intracortical) microdialysis
      studies were conducted in conscious rats to investigate the comparative
      dopaminergic and serotonergic neurotoxic potential of the pyridinium metabolite 4
      (4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium (HPP+), derived from
      the extensively used neuroleptic agent haloperidol and 1-methyl-4
      phenylpyridinium (MPP+), the pyridinium metabolite derived from the parkinsonian
      inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Although HPP+
      was less potent than MPP+ on the dopaminergic system, the two compounds displayed
      comparable toxic effects on the serotonergic system. HPP+ also proved to be a
      weaker inhibitor of mitochondrial respiration than MPP+ in vivo as measured by
      increases in extracellular lactate levels. On the other hand, HPP+ was a more
      potent inhibitor of mitochondrial respiration in vitro than MPP+, with IC50
      values of 12 microM (HPP+) and 160 microM (MPP+). Quantitative estimations
      established that the concentrations of the more hydrophobic HPP+ in the brain
      tissues surrounding the microdialysis probe were less than those of MPP+ after
      comparable perfusions. Consequently, the inherent toxicity of HPP+ relative to
      MPP+ may be greater than suggested by the results observed in the microdialysis
      experiments. These data support previous speculations that HPP+ may contribute to
      some of the persistent extrapyramidal side effects associated with chronic
      haloperidol treatment.

PMID- 8301580
TI  - Properties of the LP-805-induced potassium currents in cultured bovine pulmonary
      artery endothelial cells.
AB  - The actions of 8-tert-butyl-6,7-dihydropyrolo[3,2-e]-5- methylpyrazolo[1,5
      a]pyrimidine-3-carbonitrile (LP-805) on membrane K+ currents in cultured bovine
      pulmonary artery endothelial cells were investigated using the patch-clamp
      technique. In the whole-cell voltage clamp experiments, with 11 mM ethylene
      glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) in the
      pipette, membrane currents revealed only an inwardly rectifying K+ current, and
      no outward current could be observed at depolarized potentials. Using a pipette
      solution containing 0.3 mM EGTA, outward K+ current was present in response to
      depolarizing voltage steps from a holding potential of -60 mV. LP-805 (1-10
      microM) significantly increased outward K+ currents in a concentration-dependent
      manner. The increase of this K+ current was inhibited by 5 mM tetraethylammonium
      and 5 mM tetrabutylammonium to a level less than the control. Partial recovery
      occurred on washout. However, the increase of outward K+ current by 10 microM LP
      805 was unaffected by 5 mM 4-aminopyridine and 1 microM glibenclamide. LP-805 (1
      10 microM) significantly decreased the inwardly rectifying K+ current in a
      concentration-dependent manner. In cell-attached patches, inward single K+
      currents were recorded at negative membrane potentials, and single channel
      conductance was 23 +/- 2 pS (n = 5). No outward current could be observed at
      positive potentials. LP-805 (10 microM) inhibited the inwardly rectifying K+
      currents. Thus LP-805 inhibits inwardly rectifying K+ currents but activates
      outward Ca(++)-dependent K+ currents in bovine pulmonary artery endothelial
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301581
TI  - Glycine conjugation activity of benzoic acid and its acinar localization in the
      perfused rat liver.
AB  - Glycine conjugation activity toward benzoic acid (BA) was studied in the single
      pass perfused rat liver preparation. The steady-state hepatic extraction ratio
      for the portal vein (PV) perfused liver (at 10 ml/min) was maximal (0.6) at input
      concentrations < 40 microM among perfusions varying from tracer to 700 microM.
      Glycine conjugation was the predominant pathway; the kinetic parameters estimated
      after appropriately correcting for plasma protein binding (KA = 8.37 x 10(3) M-1
      and 1.9 sites) revealed a low Km (12 microM) and a moderately high Vmax (101
      nmol.min-1.g-1 liver) system. Biliary excretion of BA and its glycine-conjugated
      metabolite, hippuric acid, was minimal. Under first-order conditions (input
      concentration < 2 microM), the method of HAPV and HAHV perfusion (trace
      [14C]benzoate delivered via the hepatic artery (HA) at 2 ml/min and blank
      perfusate via the portal vein (PV) or hepatic vein (HV) at 10 ml/min) was used to
      examine the localization of glycine conjugation activity toward BA. During steady
      state, a multiple indicator dose of 51Cr-labeled red blood cells (vascular
      marker), [58Co]EDTA (interstitial space marker, which behaves similar to labeled
      tracer sucrose) and 3H2O (cellular marker) was injected as a bolus into the HA.
      Values of the extraction ratio of BA for HAPV perfusion (0.59 +/- 0.09) were
      dramatically reduced during HAHV perfusion (0.061 +/- 0.033, P < .01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301582
TI  - Expression and pharmacological characterization of the human D3 dopamine
      receptor.
AB  - Binding of dopamine receptor ligands to human D2 and D3 receptors was
      characterized in Chinese hamster ovary (CHO) cells using the dopamine D2 receptor
      antagonist [125I] iodosulpiride. Only limited binding selectivity was observed
      for known dopamine D2 receptor antagonists from a variety of chemical classes,
      which included haloperidol, chlorpromazine, sulpiride, pimozide and cis
      flupenthixol. The most selective compound from this group were (+)butaclamol and
      domperidone which showed 5-fold D3 selectivity. A number of high affinity
      dopamine receptor agonists, including apomorphine and bromocriptine, also failed
      to demonstrate selectivity. In contrast, the natural ligand dopamine and the
      efficacious synthetic agonists quinpirole, (+)4-propyl-9-hydroxynapthoxazine
      (PHNO), 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN), 7-OH DPAT
      and N-0434 showed marked apparent human dopamine D3 (hD3) receptor selectivity.
      In the aminotetralin series, this selectivity was observed preferentially with
      analogs of the 6,7-rotamer compared with compounds from the 5,6-rotamer series.
      Functional coupling of the hD3 receptor was investigated in a number of cell
      lines in which the hD3 receptor was stably expressed, including CHO cells, the
      neuroblastoma-glioma hybrid cell line NG108-15 and a rat 1 fibroblast cell line.
      There was no evidence of functional coupling of the hD3 receptor to adenylate
      cyclase, arachidonic acid release, phospholipase C activation, K+ currents or
      calcium mobilization in any of the cell lines examined. Furthermore, guanine
      nucleotides failed to inhibit the binding of [3H] N-0437 to hD3 receptors in any
      of the three cell lines. There may be a number of explanations for these results.
      These cell lines may not have the appropriate G-protein or secondary messenger
      systems that are coupled to the hD3 receptor in situ. Alternatively, this
      receptor may couple by a mechanism that is as yet undefined. The finding that a
      wide range of structurally diverse human dopamine D2 (hD2) receptor agonists have
      an apparent hD3 selectivity may imply that the hD3 receptor exists predominantly
      in a high affinity state.

PMID- 8301583
TI  - Cyclophosphamide-induced lung toxicity: mechanism of endothelial cell injury.
AB  - Cyclophosphamide (CP) is associated with significant pulmonary toxicity; however,
      the mechanism of toxicity is unknown. An in vitro endothelial model of injury was
      developed to assess the direct toxic effects of CP, CP derivatives and CP
      metabolites on cultured endothelial cells. Injury to 51Cr-labeled bovine artery
      pulmonary endothelial (BPAE) cells was quantified by the release of 51Cr from
      BPAE cells incubated for 18 h with injury expressed as a cytotoxic index. Because
      CP activation and metabolism occurs primarily in liver, assays assessing CP
      effects were conducted in the presence of an hepatic microsomal enzyme system.
      Upon activation, CP produces 4-hydroxycyclophosphamide, acrolein (ACR) and the
      alkylating metabolite, phosphoramide mustard. Nonactivated CP demonstrated no
      toxicity to BPAE cells within 18 h; whereas, activated CP induced significant
      BPAE cell injury in a concentration-dependent manner. Specific metabolites of CP
      4-hydroxycyclophosphamide and ACR were markedly more toxic to BPAE cells than
      phosphoramide mustard. Sulfhydryl-rich compounds, S-2-(3
      aminopropylamino)ethylphosphoric acid (WR-2721) and N-acetylcysteine,
      significantly reduced 4-hydroxycyclophosphamide- and ACR-induced injury but had
      no significant protective effect against phosphoramide mustard-induced toxicity.
      These studies suggest 1) CP is not metabolized within pulmonary artery
      endothelial cells, 2) ACR may be the principal CP metabolite involved in
      mediating direct injury to pulmonary artery endothelial cells and 3) sulfhydryl
      rich agents may be effective in reducing CP-induced damage to critical
      endothelial cell barriers.

PMID- 8301584
TI  - Characterization of antihypertensive activity of ABBOTT-81988, a nonpeptide
      angiotensin II antagonist in the renal hypertensive rat.
AB  - 2-(N-Propyl-N[(2'-[1H-tetrazol-5-yl]biphenyl-4yl)methyl]amin o) pyridine-3
      carboxylic acid (ABBOTT-81988), a novel nonpeptide angiotensin II (AII)
      antagonist, was evaluated to characterize its antihypertensive activity in the
      conscious renal hypertensive rat. Oral or i.v. administration of ABBOTT-81988 at
      0.03 to 0.3 mg/kg produced a dose-dependent, sustained decrease in mean arterial
      pressure (MAP; control 162-173 mm Hg, n = 27) of approximately 20 to 70 mm Hg. At
      a dose of 0.3 mg/kg p.o., ABBOTT-81988 lowered MAP to a normotensive level for
      more than 24 hr and did not change heart rate. During its antihypertensive effect
      (delta MAP, -28% approximately -35%), ABBOTT-81988 (0.1-03 mg/kg i.v.) decreased
      total peripheral resistance (delta resistance, -31% approximately -43%), and
      cardiac output remained either unchanged or slightly elevated. ABBOTT-81988 (0.3
      mg/kg i.v.) produced an additional antihypertensive effect (delta MAP, -12 +/-
      2%, n = 5) in captopril-pretreated (10 mg/kg i.v.) hypertensive rats, but
      captopril (10 mg/kg i.v.) had no effect in ABBOTT-81988-pretreated (0.3 mg/kg
      i.v.) rats. In the normotensive rat, ABBOTT-81988 (0.3 mg/kg p.o.) had no effect
      on basal MAP, but it inhibited the AII-induced (0.1 microgram/kg i.v.) pressor
      response by 51% to 91% for 24 hr, whereas the responses to norepinephrine (0.3
      microgram/kg i.v.), vasopressin (0.03 IU/kg i.v.) and bradykinin (3 micrograms/kg
      i.v.) were not affected. It is concluded that ABBOTT-81988 is a safe and
      efficacious AII antagonist that may have use in the treatment of human
      hypertension.

PMID- 8301586
TI  - Characterization of the serotonin1A receptor antagonist activity of WAY-100135
      and spiperone.
AB  - The effects of the putative serotonin (5-HT)1A receptor antagonists WAY-100135
      (WAY) and spiperone on the neuronal activity recorded from medullary and dorsal
      raphe 5-HT neurons and the inferior cardiac sympathetic nerve were investigated
      in chloralose anesthetized cats. We also determined the effectiveness of WAY and
      spiperone to antagonize the sympathoinhibitory effects of the 5-HT1A agonist 8
      hydroxy-(2-di-n-propylamino)tetralin (8-OH DPAT). Intravenous administration of
      both WAY and spiperone produced a dose-related inhibition of the firing of
      medullary 5-HT neurons. WAY also inhibited firing of serotonergic neurons in the
      dorsal raphe nucleus. WAY treatment had no significant effect on inferior cardiac
      sympathetic nerve discharge (SND), whereas spiperone treatment caused a small,
      but significant, increase in SND. WAY treatment did not significantly affect 8-OH
      DPAT-induced inhibition of unit firing. Spiperone, however, did display
      antagonist activity at the presynaptic autoreceptor site. WAY and spiperone
      pretreatments resulted in significant rightward shifts in the 8-OH DPAT
      inhibition of SND dose-response curves and reversed the depressant effects of 8
      OH DPAT. These results suggest that WAY and spiperone act as 5-HT1A antagonists
      postsynaptically, but WAY appears to have more potent agonist efficacy at the 5
      HT1A presynaptic autoreceptor site in the cat. However, because all drugs were
      administered intravenously, conclusions regarding direct effects of WAY and
      spiperone on 5-HT1A receptors must be made cautiously.

PMID- 8301585
TI  - Synergistic effect of nisoldipine and nitroglycerin on human internal mammary
      artery.
AB  - Perioperative spasm of the internal mammary artery (IMA) can be a problem in
      coronary artery bypass surgery, which may be prevented by vasodilator drugs. The
      relaxing effect of a new calcium antagonist nisoldipine used alone or in
      combination with nitroglycerin (NTG) was studied in human isolated IMA in organ
      chambers. The results showed that nisoldipine exhibited a potent relaxing effect
      on IMA precontracted by membrane depolarization (K+ induced) with an EC50 of 7.58
      +/- 0.08 (-log M). Nisoldipine was about 10 times more potent than was nifedipine
      (EC50, 6.72 +/- 0.10). However, both calcium antagonists showed much less
      relaxing effect on IMA precontracted with the thromboxane mimetic U46619. When
      IMA was pretreated with nisoldipine, this drug (range, 10-300 nM) inhibited
      contraction induced by either K+ or U46619 in a concentration-dependent manner.
      The relaxing effect of nisoldipine was long lasting and extremely hard to wash
      out (more than 3 hr). NTG showed a rapid and short-lasting relaxing effect on IMA
      precontracted with either K+ or U46619. Pretreatment of IMA with NTG had little
      effect for prevention of contraction to K+ or U46619. Combining nisoldipine with
      NTG at low concentrations (1-30 nM) produced a synergistic effect in the
      prevention of IMA contraction to K+ or U46619 and in relaxation of IMA
      precontracted with these agents. These studies reveal that combining nisoldipine
      with NTG combines the advantages of both and provide a scientific basis for a
      future clinical trial using combined nisoldipine and NTG at low concentrations
      for the preparation of IMA (pretreatment) to prevent IMA spasm during coronary
      artery bypass grafting.

PMID- 8301588
TI  - Orally administered glycolipid derivative LIGA20 reduces infarct volume and
      behavioral impairment after focal cerebral ischemia.
AB  - The efficacy of p.o. semisynthetic glycolipid LIGA20 (II3Neu5-AcGgOse4-2-d
      erythro-1,3-dihydroxy-2-dichloro-aceta mide-4-trans- octadecene) treatment in
      stroke was studied in a permanent left middle cerebral artery occlusion model in
      the rat. A dose-dependent increase of plasma LIGA20 and its presence in the brain
      were documented after p.o. drug application. Oral administration of 50 to 200
      mg/kg of LIGA20, initiated 24 hr before middle cerebral artery occlusion and
      continued for 7 days, reduced the motor and cognitive impairment after the
      stroke, measured by the rotarod and the passive avoidance test, respectively. The
      10-mg/kg dose was effective when given i.v. but not p.o. Oral treatment with 100
      mg/kg of LIGA20 reduced the infarct size in the cortex but not in the ischemic
      core (the striatum). No biochemical or behavioral adverse effects of LIGA20
      treatment were observed. Further studies are needed to evaluate the full
      therapeutic potential of this compound.

PMID- 8301587
TI  - NGF and anti-transferrin receptor antibody conjugate: short and long-term effects
      on survival of cholinergic neurons in intraocular septal transplants.
AB  - We describe a new molecular carrier system that allows for the transport of nerve
      growth factor (NGF) across the blood-brain barrier (BBB), as assessed by trophic
      effects on intraocular forebrain transplants that contain central cholinergic
      neurons. The carrier system involves monoclonal antibodies (OX-26) directed
      against the transferrin receptor, to which NGF molecules are covalently linked.
      Transferrin receptors are highly concentrated on brain blood vessels and
      participate in the transport of iron across the BBB. Host rats with septal
      transplants were divided into four groups, which received OX-26-NGF, OX-26, NGF
      or saline intravenously at 2, 4, 6 and 8 weeks after grafting. Half of the
      animals were killed directly after the final injection, whereas the other half
      were allowed to survive for an additional 5 months. Control experiments revealed
      that blood vessels in mature brain grafts in oculo contained large amounts of
      transferrin receptors. Covalent binding of NGF to the OX-26 antibodies did not
      impede OX-26 binding to CNS transferrin receptors, nor did conjugation affect the
      bioactivity of NGF. A time-dependent increase in host brain NGF levels was found
      after injection of OX-26-NGF into the tail vein. Host serum contained some NGF
      antibodies in the short-term OX-26-NGF group that had disappeared in the long
      term group; host adrenals showed no differences in wet weight or norepinephrine
      or epinephrine whole tissue levels in any of the groups. As previously reported,
      the overall growth of intraocular septal transplants was approximately twice as
      great in the OX-26-NGF group relative to all other groups. This difference in
      final size persisted unabated for at least 5 months after the last injection.
      Furthermore, the significantly higher numbers of choline acetyl transferase
      immunoreactive neurons in transplants of OX-26-NGF-treated hosts also persisted
      during the 5-month postinjection interval. Taken together, the data suggest that
      the OX-26 conjugate may be a unique approach to permit passage of neurotrophin
      peptides into the brain in a biologically active form.

PMID- 8301589
TI  - Comparison of kappa opioids in rhesus monkeys: behavioral effects and receptor
      binding affinities.
AB  - Bremazocine, [5R-(5,7,8 beta)]-N-methyl-N-[7-(1-pyrrolidinyl)1-oxaspiro [4,5]dec
      8-yl]-4-benzofuranacetamide (Cl-977), (+-)-trans-3,4-dichloro-N- methyl-(2
      (pyrrolidin-1-yl)-5-methoxy-1,2,3,4-tetrahydronapth++ +-1-yl benzeneacetamide
      methanesulfonate (DUP 747), ethylketocyclazocine (EKC), nalorphine, (+/-)-trans-N
      methyl-N-[2-(1- pyrrolidnyl)-cyclohexyl]benzo[b]thiophene-4-acetamide (PD117302),
      trans-(+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-
      cyclohexyl]benzeneacetamide (U-50,488), (5,7,8 beta)-N-methyl-N[2-(1-
      pyrrolidinyl), 1-oxaspiro[4,5]dec-8-yl benzeneacetamide (U-69,593) and
      spiradoline were compared in rhesus monkeys for their discriminative stimulus,
      analgesic and respiratory effects. Selected compounds also were studied for their
      binding affinities at mu [[3H](D-Ala2-Me-Phe4,Glyol5)enkephalin], kappa ([3H]U
      69,593) and delta [[3H](D-Pen2-D-Pen5) enkephalin], opioid receptors in monkey
      brain membranes. All compounds substituted completely (> or = 90%) for EKC in
      monkeys discriminating between EKC and saline, with the exception that DUP 747
      produced a maximum of 74% EKC responding. None of the compounds reversed
      naltrexone responding in morphine-abstinent monkeys; all of the compounds
      substituted for naltrexone in morphine-treated monkeys discriminating between
      naltrexone and saline, with the exception that spiradoline produced a maximum of
      68% naltrexone responding. Eight compounds produced maximum analgesic effects in
      a tail withdrawal procedure and quadazocine antagonized these effects; nalorphine
      did not have analgesic effects, but it antagonized analgesic effects of several
      other compounds. U-50,488 did not decrease respiratory function, whereas U-69,593
      decreased frequency of respiration and volume of respiration to less than 40% of
      control values; Cl-977, DUP 747, PD117302 and spiradoline had limited effects on
      respiratory function. Larger doses of each compound increased both respiration
      and motor activity.

PMID- 8301590
TI  - Effects of 17-octadecynoic acid, a suicide-substrate inhibitor of cytochrome P450
      fatty acid omega-hydroxylase, on renal function in rats.
AB  - This study evaluated the ability of 17-octadecynoic acid (17-ODYA) to inhibit the
      metabolism of arachidonic acid by cytochrome P450 in renal cortical microsomes of
      rats, and characterized the effects of intrarenal infusion of this substance on
      renal hemodynamics and the excretion of water and electrolytes. 17-ODYA was a
      potent inhibitor (IC50 < 100 nM) of the formation of 20-hydroxyeicosatetraenoic
      acid, epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids by rat renal
      cortical microsomes incubated with arachidonic acid. Infusion of 17-ODYA (16.5
      nmol/min; n = 8) directly into the renal cortical interstitium of rats produced a
      diuresis and a natriuresis which were associated with an increase in renal
      papillary blood flow in the absence of changes in renal blood flow, cortical
      blood flow or glomerular filtration rate. 17-ODYA inhibited the omega
      hydroxylation of arachidonic acid by microsomes prepared from the infused kidney
      by 61.3 +/- 9.2% (n = 7) relative to that observed in the contralateral kidney,
      whereas infusion of vehicle (n = 6) or palmitate (n = 4) had no effect on renal
      metabolism of arachidonic acid by cytochrome P450. Infusion of 17-ODYA (33
      nmol/min) into the renal artery of rats also increased urine flow and sodium
      excretion, whereas renal blood flow and glomerular filtration rate were not
      significantly altered. Papillary blood flow increased 36% during infusion of 17
      ODYA into the renal artery, and renal interstitial hydrostatic pressure increased
      from 8.7 +/- 1.1 to 13.8 +/- 1.5 mm Hg. These results suggest that endogenous
      cytochrome P450 metabolites of arachidonic acid influence renal medullary
      hemodynamics and the excretion of water and electrolytes.

PMID- 8301591
TI  - Regulation of cytochrome P-4501A and cytochrome P-4502E induction in the rat
      during the production of interferon alpha/beta.
AB  - The down regulation of constitutive hepatic microsomal cytochromes P-450 (P450)
      by interferons has been well described in experimental animals and humans,
      however the down regulation of induced forms of P450 has not been documented
      clearly. Differential down regulation of constitutive and induced P450 could
      alter the proportions of P450 enzymes and, hence, the relative
      bioactivation/detoxification of xenobiotics. We investigated the effects of
      polyinosinic acid-polycytidylic acid, a potent stimulator of interferon
      alpha/beta production on CYP1A and CYP2E induction in the rat. Polyinosinic acid
      polycytidylic acid down regulated the constitutive and pyridine-induced
      expression of CYP2E1 and the pyridine- and beta-naphthoflavone-induced expression
      of CYP1A1 as demonstrated by metabolic activity and immunoblot analyses.
      Depression of CYP2E1 and CYP1A1 protein expression by polyinosinic acid
      polycytidylic acid was accompanied by a corresponding decrease in mRNA encoding
      these proteins. Induction of CYP1A2 mRNA also was depressed. Therefore,
      interferon alpha/beta down regulated induction of members of the CYP1A and CYP2E
      subfamilies at a pretranslational level independent of the mechanism of
      induction. Induction of the CYP1A and CYP2E subfamilies did not confer resistance
      to down regulation by interferon, although the magnitude of down regulation by
      interferon appeared to be influenced by the magnitude of P450 induction. The
      potential significance of down regulation of induced P450 in the clearance of
      certain therapeutic agents and in xenobiotic bioactivation and detoxification is
      discussed.

PMID- 8301592
TI  - Pharmacological and functional characterization of D2, D3 and D4 dopamine
      receptors in fibroblast and dopaminergic cell lines.
AB  - In order to study the properties of the D2-like dopamine receptors, D2, D3 and D4
      clones were transfected into mouse Ltk- fibroblasts, CCL1.3, and a neuronal
      mesencephalic cell line, MN9D. Most of the derived antagonist and agonist
      inhibition constants were the same for a given receptor in either cell line as
      determined by saturation and competition binding experiments. The rank order
      potencies for antagonists are: eticlopride, D2 > D3 > D4; YM-09151-2, D2 = D4 >
      D3; spiperone, D2 = D3 > D4; (+)-butaclamol, D2 > D3 > D4; clozapine, D4 > D2 >
      D3; and for agonists, quinpirole, D3 = D4 > D2; 7-hydroxy-2-(di-n-propyl)
      aminotetralin, D3 > D2 = D4. Functionally, D2 stimulation increases inositol
      phosphate levels in CCL1.3 cells but not in MN9D, whereas D2 activation inhibits
      forskolin-stimulated cyclic AMP levels in both cell lines. D4 stimulation has no
      effect on inositol phosphate metabolism in either cell type, but inhibits
      adenylate cyclase in MN9D cells. Both the D2 and D4 mediated decreases in cyclic
      AMP can be blocked by preincubation with pertussis toxin. D3 does not couple to
      these pathways in either cell line. Reverse transcription/polymerase chain
      reaction techniques were used to determine the availability of cellular
      signalling systems. Both CCL1.3 and MN9D cells have high levels of G alpha i2
      expression, whereas neither cell expresses G alpha i1 or G alpha i3. These data
      imply that the D2 receptor couples to the G alpha i2 subtype in both cell lines,
      whereas D4 does not.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301593
TI  - Administration of high doses of human recombinant interleukin-2 decreases the
      expression of several cytochromes P-450 in the rat.
AB  - Human recombinant interleukin-2 (IL-2) administration is being tested in patients
      with advanced cancer. Its effects on the expression of cytochromes P-450 were
      determined in rats. IL-2 administration (1-25 x 10(6) U/kg i.v. twice daily for 1
      to 4 days) resulted in a time- and dose-dependent decrease in cytochrome P-450
      measured by the absorbance of its Fe(++)-CO complex. After 25 x 10(6) U/kg twice
      daily for 4 days, cytochrome P-450 decreased 44%; immunoreactive cytochrome P-450
      1A1 decreased nonsignificantly (22%); but cytochrome P-450 1A2 decreased 68%;
      2B1/2, 50%; 2C11, 75%; 2D1, 36%; and 3A, 70%. Aminopyrine N-demethylase activity
      decreased 53%, ethoxycoumarin O-deethylase 64%, benzo(a)pyrene hydroxylase 71%,
      ethoxyresorufin O-deethylase 42%, pentoxyresorufin O-dealkylase 81% and
      erythromycin N-demethylase 56%. In rats treated with 3-methylcholanthrene for 4
      days, IL-2 coadministration (25 x 10(6) U/kg i.v. twice daily for 4 days) did not
      decrease significantly immunoreactive cytochrome P-450 1A1 and 1A2, whereas
      cytochromes P-450 2B1/2, 2C11 and 3A decreased 39, 54 and 67%, respectively. In
      rats treated with phenobarbital for 4 days, IL-2 coadministration decreased
      immunoreactive cytochromes P-450 2B1/2 29%, whereas cytochromes P-450 1A2, 2C11
      and 3A decreased 38, 63 and 67%, respectively. We conclude that administration of
      high doses of IL-2 decreases the expression of several cytochromes P-450 in rats.
      Microsomal enzyme inducers appear to limit the effects of IL-2 on the induced
      forms of cytochromes P-450. Because much lower doses are used in humans, their
      potential effects on drug metabolism cannot be assessed from present results.

PMID- 8301594
TI  - Neural and endocrine mechanisms of cocaine-induced 70-kDa heat shock protein
      expression in aorta and adrenal gland.
AB  - Cocaine has properties of a physiologic stressor that are reflected by its
      ability to activate both the hypothalamic-pituitary-adrenal axis and the
      sympathetic nervous system. We have previously reported that activation of the
      hypothalamic-pituitary-adrenal axis and sympathetic nervous system by restraint
      and pharmacologic agents induces expression of a set of highly conserved cellular
      stress response proteins (heat shock proteins, HSP) in the adrenal gland and
      aorta. In the adrenal gland, HSP expression appears to be mediated by stress
      induced increases in adrenocorticotropic hormone whereas expression in the aorta
      involves noradrenergic neurotransmission. In this report we capitalize on the
      ability of cocaine to stimulate physiologic stress responses to define further
      mechanisms regulating HSP70 expression in these tissues. We report the novel
      observation that cocaine administration induces both adrenal and vascular HSP70
      mRNA expression. Elevated HSP70 mRNA was preceded by activation of factors
      capable of binding to the heat shock transcriptional control element and was
      followed by an elevation in HSP70 protein. Cocaine significantly increased plasma
      adrenocorticotrophic hormone whereas hypophysectomy eliminated cocaine-induced
      expression in the adrenal gland suggesting that in this tissue, the effect of
      cocaine on HSP70 expression is also mediated via adrenocorticotrophic hormone. In
      the aorta, depletion of catecholamines by reserpine pretreatment paradoxically
      augmented cocaine-induced HSP70 expression. Based on these results, it appears
      that HSP70 expression in the aorta occurs through direct actions of cocaine on
      vascular cells that are ultimately transduced to activation of the HSP70 gene
      rather than indirectly through alterations in catecholamine reuptake and
      release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301595
TI  - Multiple transport systems for organic anions across the bile canalicular
      membrane.
AB  - Multiplicity for the transport of organic anions across the bile canalicular
      membrane was studied in vivo and in vitro using dibromosulfophthalein (DBSP),
      [14C]cefodizime, [3H]leukotriene C4 (LTC4) and indocyanine green (ICG) as model
      compounds in rats. A high concentration of DBSP in plasma reduced the biliary
      excretion of cefodizime and leukotriene radioactivity to about 15 and 35% of
      their control values, respectively, but did not affect the excretion of ICG. A
      high plasma concentration of ICG reduced the excretion of cefodizime to about 60%
      of the control value, but exerted minimal effect on the excretion of leukotriene
      radio-activity and DBSP. In vitro, ATP-dependent uptake of LTC4 into the
      canalicular membrane vesicles was reduced by DBSP, cefodizime and ICG in a dose
      dependent manner, with approximate IC50 values of 0.1 microM, 10 microM, and 1
      microM, respectively. The hepatic unbound concentration of DBSP sufficient to
      reduce the excretion of cefodizime, leukotriene radioactivity and DBSP itself in
      vivo was calculated to be approximately 10 microM, a concentration which was also
      sufficient to reduce the transport of LTC4 in vitro. In contrast, the hepatic
      unbound concentration of ICG that saturated the excretion of ICG in vivo was
      calculated to be less than 0.1 microM, which was more than ten times smaller than
      the IC50 of ICG for the transport of LTC4 in vitro. These results suggest the
      presence of multiple systems for the transport of organic anions across the bile
      canalicular membrane: one is the predominant transport system for DBSP and
      cefodizime, which also accepts LTC4 as a substrate; the other is the primary
      transport system for ICG, which is distinct from that for DBSP, cefodizime and
      LTC4, although some overlap in the substrate specificity may be observed between
      the two systems.

PMID- 8301596
TI  - Delta-1 opioid receptor dependence of acute hypoxic adaptation.
AB  - Previously an acute adaptation to hypoxia was induced by intermittent, severe
      hypoxia and this conditioned increase in survival time during subsequent hypoxia
      was blocked by naloxone. The current study further defined the opioid nature and
      the receptor type(s) involved in hypoxic adaptation by the use of (+)-naloxone
      (inactive isomer) and selective opioid antagonists. (+)-Naloxone failed to change
      significantly the survival times of hypoxic or sham conditioned mice during
      subsequent hypoxia. The selective opioid antagonists, 7-benzylidenenaltrexone,
      naltrindole, beta-funaltrexamine and norbinaltorphimine were administered
      subcutaneously before hypoxic or sham conditioning. The delta-1 and delta-2
      selective antagonists, 7-benzylidenenaltrexone and naltrindole respectively,
      blocked the hypoxic conditioning-induced increase in survival time. The lowest
      effective 7-benzylidenenaltrexone dose was 3000-fold lower than the lowest
      effective naltrindole dose indicating that the acute adaptation to hypoxia was
      predominantly sensitive to delta-1 blockade. Neither the mu antagonist, beta
      funaltrexamine, nor the kappa antagonist, norbinaltorphimine, significantly
      changed survival time in sham or hypoxic conditioned mice. These results support
      a delta-1 receptor mediated mechanism of acute adaptation to hypoxia.

PMID- 8301597
TI  - Dose- and time-dependent cardiovascular responses induced by ethanol.
AB  - Four groups of male Sprague-Dawley rats (10/group) were instrumented to permit
      access to venous and arterial blood and comprehensive cardiovascular measurements
      for 4 h after intragastric administrations of water or 2, 4 or 6 g/kg of ethanol.
      Maximum blood concentrations for each increasing dose occurred within 45 min
      after ethanol attaining peaks of 63 +/- 8, 103 +/- 11 and 221 +/- 33 mg/d,
      respectively. Cardiac outputs were significantly lower than the control group
      beginning at 15 min for 4 and 6 g/kg and at 120 mins for 2 g/kg with similar
      effects on stroke volume for the three doses. Systemic vascular resistance and
      heart rate were consistently increased throughout the 4 h for the 6 g/kg group.
      There was a delayed mean arterial blood pressure decrease in the 6 g/kg group
      beginning at 120 min after ethanol with significant effects in the 4 g/kg group
      at 60 and 120 min. Decreased central venous pressure and respiration rate
      prevailed during the 4 h after 6 g/kg. Blood glucose concentrations were elevated
      at 60 min after 6 g/kg and at 240 min for all doses. However, blood temperatures
      were consistently lower than the control group after all three doses beginning 45
      min after the drug. These data demonstrate that ethanol evokes cardiovascular,
      respiratory and metabolic changes that are both dose- and time-dependent. Cardiac
      output and systemic vascular resistance are significantly affected suggesting a
      marked alteration of peripheral blood flow.

PMID- 8301598
TI  - Inhibition by capsazepine of resiniferatoxin- and capsaicin-induced contractions
      of guinea pig trachea.
AB  - The site of action of resiniferatoxin (RTX) and capsaicin and the pharmacological
      consequences of the resultant tachykinin release were examined in the guinea pig
      trachea. RTX and capsaicin were both potent and efficacious contractors of
      isolated tracheal smooth muscle. RTX was about 20-fold more potent than
      capsaicin, with -log (M) EC50 values of 8.88 +/- 0.09 (n = 14) and 7.55 +/- 0.07
      (n = 14), respectively. The putative capsaicin receptor antagonist capsazepine
      (10 microM) effectively inhibited responses to both RTX and capsaicin in a
      competitive fashion. The -log (M) pKB values for capsazepine against
      resiniferatoxin and capsaicin were 6.28 +/- 0.25 and 6.04 +/- 0.13, respectively.
      Contractile responses to RTX and capsaicin were unaffected by the NK-1 antagonist
      CP 96345 (0.3 microM), partially inhibited by the NK-2 antagonist SR 48968 (0.3
      microM) but nearly abolished by a combination of the antagonists. Capsaicin and
      RTX desensitized tissues to subsequent additions of either capsaicin (1 microM)
      or RTX (0.1 microM). Capsaicin showed maximal desensitization at 1 microM, and
      RTX at 0.1 microM. This study shows that RTX is a potent activator of capsaicin
      sensitive tachykinin-containing nerves in the airways. The site of action of RTX
      and capsaicin appears to be a receptor sensitive to capsazepine. Moreover, RTX
      and capsaicin both release tachykinins that act on both NK-1 and NK-2 receptor
      subtypes.

PMID- 8301599
TI  - The cardioprotective effects of R 75231 and lidoflazine are not caused by
      adenosine A1 receptor activation.
AB  - The goal of this study was to determine the cardioprotective profile for the
      nucleoside transport inhibitor 2-(aminocarboxyl)-N-(4-amino-2,6-dichlorophenyl)-4
      [5,5-bis(4- fluorophenyl)pentyl]-1-piperazinylacetamide trihydrochloride-2,5
      hydrate (R 75231) in isolated rat hearts and whether its protective effects are
      caused by adenosine A1 activation. R 75231 increased time to contracture during
      global ischemia in a concentration-dependent manner (EC25 = 2.6 microM) that was
      comparable to the structurally related compound lidoflazine (EC25 = 1.2 microM).
      R 75231 caused only modest improvements in reperfusion contractile function,
      whereas it profoundly reduced LDH release. The cardioprotective effects of R
      75231 were accompanied by preischemic negative inotropy with modest bradycardic
      effects. Adenosine also increased time to contracture, although it was not very
      potent (EC25 > 300 microM), and this effect was accompanied by significant
      preischemic bradycardia without measurable negative inotropic activity. Both the
      preischemia bradycardia and increase in ischemic time to contracture with
      adenosine were abolished completely by the A1 blocker 8-cyclopentyl-1,3
      dipropylxanthine. The adenosine-induced increase in time to contracture was
      reversed partially by glybenclamide. Neither the pre- nor postischemic effects of
      R 75231 were abolished by 8-cyclopentyl-1,3-dipropylxanthine or glybenclamide,
      except for the preischemic bradycardia. Similar results were observed for
      lidoflazine. Thus, the cardioprotective effects of R 75231 are not mediated by
      adenosine A1 receptor activation and, thus, probably are not caused by its
      activity as a nucleoside transport inhibitor. It may be acting as a calcium
      antagonist in this model.

PMID- 8301600
TI  - Coronary vascular effects of cocaine in rats.
AB  - It has been suggested that ischemia secondary to coronary vasoconstriction is
      responsible for adverse cardiovascular effects of cocaine. However, the reported
      coronary vascular effects of cocaine vary considerably. We sought to determine
      the effects of cocaine on the coronary vasculature in anesthetized and conscious
      rats. Rats anesthetized with chloralose were instrumented for estimation of
      ascending aortic and coronary blood flows using pulsed Doppler velocitometry.
      Cocaine administration resulted in bradycardia and a biphasic mean arterial
      pressure response. Cocaine elicited highly variable increases in coronary
      vascular resistance and decreases in cardiac output. Decreases in coronary blood
      flow and rate-pressure product were directly correlated. Prazosin significantly
      attenuated the cardiac output but not the coronary vascular responses to cocaine.
      Propranolol, on the other hand, significantly shortened the duration of both
      responses. Conscious rats, instrumented for coronary blood flow determination,
      also exhibited cocaine-induced increases in coronary vascular resistance, yet the
      changes in coronary blood flow were not correlated with the rate-pressure
      product. These results provide the first evidence that cocaine produces
      equivalent increases in coronary vascular resistance in conscious and
      anesthetized rats. However, because the relationship between coronary blood flow
      and rate-pressure is different between the two preparations, as are other
      cardiovascular responses, we suggest that anesthesia alters the mechanism(s) by
      which cocaine affects the rat coronary vasculature.

PMID- 8301601
TI  - Proceedings of the Physiological Society meetings of 30 June-2 July and 27-29
      September 1993.

PMID- 8301602
TI  - Metastases to the oral mucosa: analysis of 157 cases.
AB  - A review of the English-language literature revealed 157 well-documented cases of
      metastatic lesions to the oral mucosa. Most (64%) were diagnosed in patients in
      their fifth to seventh decade. The frequency of the primary site differed between
      genders: for men it was the lung (35.5%) followed by the kidney (16%) and skin
      (15%); for women it was the breast (24%) followed by the genital organs (17%).
      The most common oral site was the gingiva and alveolar mucosa (54.8%) followed by
      the tongue (27.4%), and with much less frequency by the tonsil, palate, lip,
      buccal mucosa and floor of the mouth. Of the dentulous patients, 79% exhibited
      the metastatic tumor in the attached gingiva. The clinical appearance of the
      metastatic oral lesion in most cases resembled hyperplastic or reactive lesions.

PMID- 8301603
TI  - Acyclovir: is it an effective virostatic agent for orofacial infections?
AB  - Oral and intravenous acyclovir formulations provide effective virostasis against
      many herpes viruses infections, especially severe herpes simplex or varicella
      zoster infections in ambulatory and immunocompromised patients. The therapeutic
      virostatic efficacy of topical acyclovir formulations requires further
      development, however, especially for orolabial herpetic infections.

PMID- 8301604
TI  - Giant cell lesions of the jaws: evaluation of nucleolar organizer regions in
      lesions of varying behavior.
AB  - To examine whether giant cell lesions of the jaws (GCL) of varying behavior could
      be separated histologically, a number of GCL were studied using the AgNOR
      staining technique for nucleolar organizer regions. The mean AgNOR count of
      mononuclear cells from recurrent lesions (1.73 +/- 0.15) was slightly higher than
      that of the aggressive lesions (1.54 +/- 0.21) and much higher than that of the
      non-aggressive/non-recurrent lesions (1.33 +/- 0.14). Similarly, the mean AgNOR
      count of the multinucleate giant cells of the recurrent lesions (1.52 +/- 0.14)
      was slightly higher than that of aggressive lesions (1.34 +/- 0.092) and much
      higher than that of non-aggressive/non-recurrent lesions (1.26 +/- 0.05).
      Statistical analysis showed a significant difference between the mean number of
      AgNORS of recurrent lesions and non-recurrent/non-aggressive ones in both the
      mononuclear and multinuclear population (p < 0.05).

PMID- 8301605
TI  - Immunohistochemical localization of bone morphogenetic protein (BMP) in
      calcifying fibrous epulis.
AB  - Immunohistochemical detection of bone morphogenetic protein (BMP) in calcifying
      fibrous epulis was performed to elucidate the biological process of ossification
      and cemento-ossification. In a total 25 cases, 15 (60%) showed positive BMP
      staining in bone forming areas. Histopathological features of developing hard
      tissues were varied, consisting of structures such as woven bone and cemento
      osseous formations. BMP immunostaining was limited to osteoblasts and fibrous
      connective tissue surrounding the bone matrix. BMP was concentrated in the
      periodontal fibres and in dense fibrous structures in the cemento-osseous masses.
      On the basis of histopathological and immunohistochemical features, the
      histogenesis of ossifying and cemento-ossifying processes appear to be of two
      possible origins; the excessive proliferation of periodontal ligament and a
      metaplastic process occurring in the connective tissue fibres (non-periodontal in
      origin), with the former being more common.

PMID- 8301606
TI  - Ultrastructure of wound healing following direct pulp capping with calcium-beta
      glycerophosphate (Ca-BGP).
AB  - Tissue changes in rat incisors after direct pulp capping with calcium-beta
      glycerophosphate (Ca-BGP) have been studied using light and electron microscopy.
      Immediately after pulp capping, Ca-BGP was converted to hydroxyapatite (HAP) at
      the cavity floor. At Day 1, the exposure site was covered with Ca-BGP-mediated
      mineralized tissue. Osteodentine had developed below this mineralized tissue at
      Day 3. Matrix vesicles (MV) were observed in the extracellular matrix between
      large cells and osteodentine. At Day 5, tubular dentine was observed below the
      osteodentine. Three days after the application of Ca(OH)2 in a control
      experiment, osteodentine had formed below the necrotic zone; however, tubular
      dentine was not observed at Day 5. These findings suggest that the applied Ca-BGP
      might be the source of Ca and inorganic phosphate (Pi) through hydrolysis by
      alkaline phosphatase (ALP), and that Ca-BGP-mediated mineralized tissue induces
      the early formation of tubular dentine.

PMID- 8301607
TI  - The prevalence of oral candidiasis in HIV-infected individuals and dental
      attenders in Edinburgh.
AB  - This study prospectively assessed the prevalence of oral candidal carriage and
      oral candidiasis in known HIV-seropositive individuals (n = 121) and other dental
      attenders in Edinburgh (n = 614). Candida species were isolated from 57.4% of
      dental attenders and 93.4% of HIV-seropositive subjects. Clinical evidence of
      oral candidiasis was observed in 6% and 52% of these groups respectively,
      erythematous forms of candidiasis being the commonest in both groups.

PMID- 8301608
TI  - Oral cancer development in patients with oral lichen planus.
AB  - There has been considerable controversy as to whether oral lichen planus (LP) has
      a premalignant potential. This study retrospectively examined the records of 241
      British patients with histologically confirmed LP seen during the 10-year period
      1982-92. Nine patients (3.7%) were known to have developed well-differentiated
      invasive carcinoma or carcinoma in situ in an area of LP. Most carcinomas at
      presentation were in areas of atrophic and/or erosive LP, 6 were in patients
      older than 65 years, and 6 were on the tongue. The results support a small but
      clinically important premalignant potential for LP.

PMID- 8301609
TI  - Inhibition of human oral squamous carcinoma cell (SCC-25) proliferation by
      prostaglandin E2 and vitamin E succinate.
AB  - The primary objective of this investigation was to study the effect of D-alpha
      tocopherol acid succinate (vitamin E succinate) and prostaglandin E2 (PGE2),
      individually and in combination, on the proliferation of human tongue squamous
      carcinoma cells (SCC-25) in vitro. Test compounds in varying concentrations were
      incubated with cells in serum-free Dulbecco's Modified Eagle's Medium-Ham's F-12
      Medium (50:50), supplemented with 0.1% albumin for sixteen hours. Cell
      proliferation was measured by the incorporation of [3H] thymidine in acid
      insoluble material (i.e. DNA). Prostaglandin E2 and vitamin E succinate,
      individually at 10(-9)-10(-6) M, caused significant dose-dependent inhibition in
      DNA synthesis. A combined dose of each compound at 10(-5) M resulted in
      significant additive inhibition which averaged 43.53% (p < 0.005). Addition of
      indomethacin (INDO) to cell cultures induced significant dose-dependent
      stimulation in DNA synthesis. Hence, we might suggest that the overall potential
      of vitamin E in controlling malignant cell proliferation in vivo could be due to
      its own effect combined with that of endogenous PGs which are normally produced
      in excessive amounts by malignant cells.

PMID- 8301610
TI  - Ultrastructural finding of vascular degeneration in myositis ossificans
      circumscripta (fibrodysplasia ossificans).
AB  - A case of myositis ossificans circumscripta (fibrodysplasia ossificans) of the
      masseter muscle has been studied ultrastructurally. It showed atrophy of muscle
      fibres with deranged myofilaments, adjacent to dense fibrous tissue, osteoid and
      bone. A large number of the cells found in the dense fibrous tissue showed
      vacuolation and separation of membrane bound vesicles similar to matrix vesicles
      released by chondroblasts and osteoblasts during calcification. It is possible
      that, as in normal calcification of bone, these vesicles are responsible for
      initiating calcification in the ectopic bone found in the present condition. It
      was also shown that most of the blood vessel found in the blocks examined
      exhibited various degrees of degenerative changes. The finding of arterial
      occlusion together with capillary degeneration suggests that the main changes in
      myositis ossificans circumscripta may be those affecting blood vessels leading to
      ischaemic muscle atrophy. The fibrosis and ossification that follow are probably
      secondary changes.

PMID- 8301611
TI  - [Cardiovascular adaptation in micro-gravity environment].

PMID- 8301612
TI  - [The EEG pattern in the growing Japanese black calves].
AB  - Developmental EEG examination was performed in ten Japanese Black calves aged
      from 1 week to 10 weeks. The EEG was markedly influenced by the level of
      consciousness. In the alert wakefulness, the EEG was high frequency, low voltage
      pattern. In the wakefulness, the dominant activity was low frequency, and low
      voltage, high frequency activity was superimposed. In the drowsiness, the EEG was
      high voltage, low frequency activity pattern. In the sleep, markedly high
      voltage, low frequency activity was dominant. These four EEG patterns observed
      from the 1st week to the 10th week. During the course of the examination, high
      frequency, low voltage activity increased, so the EEG pattern gradually developed
      to the 10th week of age. In the wakefulness, theta wave and alpha wave dominant
      pattern was observed in seven calves. This pattern was observed after the 2nd
      week of age, thereafter incidence of this pattern increased to the 5th or 6th
      week. The frequency of theta wave and alpha wave dominant pattern increased from
      6.0-7.5 Hz at the 3rd week to 7.5-9.0 Hz at the 10th week. As described above,
      the development of the central nervous system has attained the considerable level
      in the newborn calves, and thereafter continue to develop.

PMID- 8301613
TI  - [Visual evoked potentials (VEPs) by leadings on scalp and dura in rabbits].
AB  - Visual evoked potentials (VEPs) were obtained from five rabbits. Responses to the
      photic stimulation were recorded by leading on scalp and dura. Stimulating
      conditions were changed in order of binocular, monocular (left and right) and
      screened binocular. The VEP waveforms leading on scalp and dura were composed of
      five positive and four negative peaks. The amplitude of the VEP leading on dura
      was about five times larger than that of the VEP leading on scalp. The VEP evoked
      by the monocular stimulation was characterized by the decreased amplitude in the
      ipsilateral hemisphere to the stimulated eye. It is furthermore characteristic in
      the dural recording that the major negative peaks in the early component
      disappeared in the same side as the stimulated eye. These differences in the VEP
      evoked by the monocular stimulation might reflect that the most projection of
      optic nerve cross at the optic chiasm in rabbits.

PMID- 8301614
TI  - Adolescents' cognitions and attributions for academic cheating: a cross-national
      study.
AB  - We examined perceptions about academic cheating in comparable 11th-grade students
      from Costa Rica, Germany, and the United States to assess the similarities and
      differences associated with the different societies, with achievement status, and
      with gender. German students generally differed substantially from both Costa
      Rican and U.S. students in perceptions of the problem, critical attributes of
      cheating, causes of cheating, and beliefs about effective ways to control
      cheating in the school. We did find some important similarities across all three
      samples, however. Achievement and gender effects were less substantial but were
      uniform across the three groups.

PMID- 8301615
TI  - Effects of HIV/AIDS information on attitudes toward AIDS: a cross-ethnic
      comparison of college students.
AB  - College students (N = 274) from five ethnic groups were administered an AIDS
      information questionnaire and the Attitudes Toward AIDS Scale (ATAS; Goh, in
      press) to determine the effects of AIDS information on attitudes toward AIDS. A
      series of chi-squares and multivariate analyses of variance indicated significant
      differences among ethnic groups on the usage of HIV/AIDS information, the self
      reported degree of knowledge about HIV/AIDS, measured knowledge about HIV/AIDS,
      and HIV/AIDS-related attitudes. Besides ethnicity, access to HIV/AIDS information
      and self-reported degree of knowledge about AIDS had significant effects on a
      person's measured knowledge of and attitudes toward HIV/AIDS.

PMID- 8301616
TI  - First names and perceptions of physical attractiveness.
AB  - I examined the impact of first names on ratings of physical attractiveness as
      judged by British undergraduate subjects using male and female full-face pictures
      presented on photographic slides. The photographs were identified with attractive
      names, unattractive names, or without any name indicated. Subjects rated the
      stimulus figures for physical attractiveness. Names accounted for approximately
      6% of the variance in subjects' ratings of physical attractiveness. This effect
      was highly significant for pictures of women (p < .001), but nonsignificant for
      pictures of men (p > .05).

PMID- 8301617
TI  - Being female and less deviant: the direct and indirect effects of gender on
      alcohol abuse and tobacco smoking.
AB  - We explored the deviance gender gap in relation to alcohol abuse and tobacco
      smoking with a national sample of adults. Sex role theory inspired the hypotheses
      that much of the influence of gender on deviance is conveyed through the
      relationship of gender to social bonds and to the experience of physical violence
      in childhood. Our results indicated that being female was positively associated
      with belief and attachment bonds that inhibited alcohol abuse and smoking and
      negatively associated with the experience of physical violence as a child, which
      promoted alcohol abuse and smoking.

PMID- 8301618
TI  - Relationship of childhood sexual abuse to borderline personality disorder,
      posttraumatic stress disorder, and multiple personality disorder.
AB  - In this article, I have reviewed recent research into the relationship between
      childhood sexual abuse and borderline personality disorder, posttraumatic stress
      disorder, and multiple personality disorder. Evidence that such a relationship
      exists appears convincing.

PMID- 8301619
TI  - Effects of gender on the physical attractiveness stereotype.

PMID- 8301620
TI  - The effect of major railway accidents on the psychological health of train
      drivers--I. Acute psychological responses to accident.
AB  - The acute psychological reactions of 101 train drivers to on-the-track accidents
      were studied by means of clinical interviews and questionnaires (Impact of Event
      Scale, GHQ-20 and a questionnaire addressing stress symptoms, pre-accident
      expectancies and worries). More than half of the train drivers reported moderate
      to high intrusive distress (mean 11.3) within hours to days after the accident
      but only 1/3 reported symptoms of acute psychophysiological arousal. Intrusive
      symptoms related to visual impressions were most frequently reported. Avoidance
      was less prevalent (mean 8.8). Clinical interviews, relationship between pre
      accident worries and severity of the acute responses and positive correlation
      between GHQ-scores relating to the fortnight preceding the accident and IES
      intrusion scores, suggest that premorbid variables may influence the stress
      response. Involvement in more than two previous accidents invoked a feeling of
      vulnerability and produced stronger acute responses. Post-accident experiences
      involving various personal contacts did not correlate with the stress responses
      in this study and only a few drivers experienced such events in a negative way.
      Denial of the possibility of being involved in accidents was not associated with
      increased risk of strong acute responses, indicating that denial does not predict
      poor outcome in healthy persons exposed to situations where possibility of
      avoiding the event is outside the control of the person.

PMID- 8301621
TI  - The effect of major railway accidents on the psychological health of train
      drivers--II. A longitudinal study of the one-year outcome after the accident.
AB  - The psychological impact on 101 train drivers of accidents causing major injuries
      or death to persons was studied by means of clinical interviews and
      questionnaires (Impact of Event Scale, General Health Questionnaire and a
      questionnaire addressing stress symptoms plus past and pre accident expectancies
      of being involved in accidents). The drivers were examined within hours to a few
      days after the accident and later at 1 month and 1 year. One month after the
      accident the symptoms of distress were significantly reduced and most so among
      the drivers with no preaccident risk experience according to self reports during
      the acute phase. A minor further reduction of distress was found at 1 year.
      Drivers with two or more previous accident experiences and those who had worried
      about being involved in accidents showed highest symptoms of distress at follow
      up. Eleven out of 101 drivers reported sick leave more of than 1 week after the
      accident and this was related to higher intrusion scores. The few drivers who
      report longterm psychological distress are best predicted by a combination of
      acute high IES scores, experience of previous accidents and risk expectancy prior
      to the current accident. The study suggests that premorbid and non-accident
      related variables are more important for the 1 year psychological outcome of
      healthy drivers after on-the-track accidents than the stress event itself.

PMID- 8301622
TI  - Neuropsychiatric aspects of HIV-1 infection in gay men: controlled investigation
      of psychiatric, neuropsychological and neurological status.
AB  - The aim of this study was to determine whether HIV infection is associated with
      psychiatric morbidity or neuropsychological impairment in asymptomatic and early
      symptomatic stages of disease in gay men. The subjects were 100 gay men (68 HIV
      ve, 32 HIV+ve, 6 being CDC IV). All subjects were recruited at the time of
      requesting their first HIV test and the assessment was double-blind to HIV
      serostatus. There were no differences in psychiatric status or neuropsychological
      performance between the HIV-ve and HIV+ve groups. Multiple regression analysis
      and logistic regression were used to identify factors associated with psychiatric
      morbidity, neuropsychological impairment and subjective reporting of memory
      problems and physical symptoms for all 100 subjects. Previous psychiatric history
      and current illegal (non-dependent) drug use were associated with psychiatric
      morbidity, poor education was associated with neuropsychological impairment and
      psychiatric status (score on HAD and PSE) was associated with subjective
      reporting of memory problems and physical symptoms.

PMID- 8301623
TI  - Hormonal and blood glucose responsiveness as an indicator of specific emotional
      arousal in type 1 diabetics.
AB  - The aim of the present study was to examine, whether individual emotional arousal
      induced by a specific stress interview may effect growth hormone (GH), cortisol,
      catecholamine and blood glucose levels in diabetes patients. To test the validity
      of this hypothesis we subjected 18 Type 1 diabetics and 18 healthy controls to a
      life event interview which produces individual arousal. During this stress
      interview catecholamines and plasma cortisol levels showed no significant
      increase, whereas there was a significant increase of GH over time in both group
      (p < 0.04), with a trend in diabetics to have a more marked GH response than
      controls (p < 0.10). Blood glucose levels remained unaffected by the interview.
      Depressed diabetics showed significantly higher cortisol increases (p < 0.004)
      than non-depressed diabetics, whereas there was no difference among depressed and
      non-depressed controls. Depression was not associated with an increase of other
      hormones or blood glucose levels in both groups. The results of our study confirm
      specific pathways in which individual emotional arousal and depression may lead
      to chronic metabolic disturbances as a result of GH and cortisol hypersecretion.

PMID- 8301624
TI  - Stress-induced reactivation of latent herpes simplex virus infection in rat
      lumbar dorsal root ganglia.
AB  - Clinical reports suggest that stress precipitates recurrent cutaneous Herpes
      simplex virus (HSV) infection, presumably by reactivating latent infection in
      sensory ganglia with subsequent centrifugal axonal spread to the skin. As an
      initial test of this hypothesis, rats with latent HSV, type-1, (HSV-1) infection
      in lumbar dorsal root ganglia (DRG) were exposed to a well-characterized acute
      stressor that produced gastric ulcers (U) and elevated plasma corticosterone (CS)
      concentrations. Stress-induced reactivation of latent HSV infection was suggested
      by the earlier appearance of cytopathic effect (CPE) in human foreskin fibroblast
      monolayers co-cultivated with ganglia from stressed rats than from nonstressed
      ones (4.5 +/- 0.2 and 6.4 +/- 0.4 [mean +/- SEM] days respectively; p < 0.001).
      No CPE was detected in monolayers co-cultivated with ganglia from non-infected
      rats. These initial results suggest that acute stress reactivates latent HSV-1
      ganglionic infection.

PMID- 8301625
TI  - Does a highly diluted homoeopathic drug act as a placebo in healthy volunteers?
      Experimental study of Belladonna 30C in double-blind crossover design--a pilot
      study.
AB  - A basic tenet of homoeopathy is that remedies which do not contain active
      molecules can have effects on the healthy human organism, by virtue of the
      specific preparation process of stepwise dilution and succussion, called
      potentization. The claim that a so called high 'potency' of a homoepathic remedy,
      Belladonna C30, could produce effects different from placebo, was investigated in
      a pilot study. In a double-blind crossover trial, 4 weeks of Belladonna C30 were
      compared to 4 weeks of placebo in 47 healthy volunteers. Data were collected
      daily. The number and types of changes were recorded into a predefined category
      system. Single-case evaluation showed differences between the two experimental
      phases for 21 subjects. Group evaluation showed no clearcut differences. The
      claim that homoeopathic potencies can produce symptoms other than placebo in
      healthy subjects should be put to further scrutiny.

PMID- 8301626
TI  - Rationality, emotional expression and control: psychometric characteristics of a
      questionnaire for research in psycho-oncology.
AB  - In some studies rationality, anti-emotionality and the control of (negative)
      emotions were found to be psychological risk factors for cancer. In the present
      study instruments were developed in order to cross-validate the role of the
      'rationality/anti-emotionality (RAE)'-concept and the 'emotional expression and
      control (EEC)'-concept. The psychometric characteristics of a RAE-scale and EEC
      scales were investigated in 4302 healthy women attending a breast cancer
      screening programme in The Netherlands. Principal components analysis revealed
      three factors for the RAE-scale: (1) Rationality; (2) Emotionality; and (3)
      Understanding. The EEC-scales consist of three factors that indicate: (1)
      expression of emotions to oneself; (2) expression of emotions towards others; and
      (3) control of emotions. These RAE and EEC scales can be of importance in psycho
      oncological research, especially when: (1) the more refined subscales are used;
      and (2) age of the subjects is taken into account.

PMID- 8301627
TI  - Sexual abuse as a factor in anorexia nervosa: evidence from two separate case
      series.
AB  - Evidence of a link between reported sexual abuse and specific eating behaviours
      was considered in 100 anorexic women. The women were assessed as part of case
      series from two separate clinics. There was a strong association between reported
      unwanted sexual experiences and purging behaviours (vomiting and/or abusing
      laxatives). Anorexics who did not purge had lower reported rates of abuse. The
      pattern and prevalence rate of reported abuse were similar in the two clinics,
      suggesting that the association was not a product of a specific method of
      eliciting disclosure. Implications for treatment and possible causal mechanisms
      behind this relationship are discussed.

PMID- 8301628
TI  - Management of chronic achilles tendon infection with musculotendinous gracilis
      interposition free-flap coverage.
AB  - Management of infected Achilles tendon repair poses a significant reconstructive
      problem. Thorough debridement is most important and resection of non-viable
      tendon substance is required. Reconstruction of such tendon defects requires
      vascularized soft-tissue coverage that is stable and that offers the possibility
      of functional restoration. Gracilis free-tissue transfer is an effective means of
      providing stable, durable, well-vascularized, soft-tissue coverage in an infected
      Achilles tendon repair. The microsurgical anastomoses are technically
      straightforward. Cybex II dynomometer measurements, performed 6 months following
      free-tissue transplantation, revealed strength (torque) and power, at an angular
      velocity of 45 degrees per second, of: 59 percent and 52 percent, respectively,
      compared to the uninjured side. Endurance was assessed at an angular velocity of
      120 degrees per second over a 15-second test interval, and was noted to be 81
      percent, compared to the normal ankle. Excellent functional results and
      acceptable soft-tissue contour can be expected with this technique.

PMID- 8301629
TI  - Successful upper labial replantation after 17 hours of ischemia: case report.
AB  - This report presents successful replantation of the upper lip after 17 hours of
      ischemia. In spite of successful venous anastomoses, the postoperative use of
      leeches was necessary because of severe congestion. However, sensory and
      functional recovery was excellent.

PMID- 8301630
TI  - Surgical tattooing as an aesthetic improvement in facial reconstruction with a
      free radial forearm flap.
AB  - Free flaps are usually needed for the reconstruction of extensive facial burns,
      but the final result is often a poor texture and color match. The authors report
      a burn case managed with a radial forearm free flap. The aesthetic result was
      improved by surgical tattooing of the flap, including the appearance of a beard.

PMID- 8301631
TI  - Clinical applications of acute intraoperative arterial elongation.
AB  - This study reports four clinical cases in which acute intraoperative,
      extraluminal, arterial elongation was utilized. This technique was developed to
      facilitate end-to-end anastomoses across vascular defects traditionally bridged
      with vein grafts. In the reported cases, arterial defects, ranging from 17 to 25
      mm, were closed primarily following the application of this technique. Follow-up,
      ranging from 3 to 34 months, has demonstrated patency in all cases. The authors
      believe this technique can be used clinically as a reliable alternative to vein
      grafting for the reconstruction of certain arterial defects.

PMID- 8301632
TI  - Sciatic nerve regeneration across gaps within collagen chambers: the influence of
      epidermal growth factor.
AB  - The effects of Epidermal Growth Factor (EGF) on axonal regeneration of a
      sectioned sciatic nerve within collagen tubes were investigated in 15 rats.
      Following baseline electrophysiologic assessment, bilateral 7-mm nerve gaps were
      created and repaired by interposition of collagen tubes, into which EGF (left
      side) or type I collagen (right side) was instilled. After 4 or 8 weeks, axonal
      regeneration, measured by electrophysiologic and histologic means, was identical
      for the EGF and control legs. The conclusion is that EGF does not influence nerve
      regeneration within a collagen chamber.

PMID- 8301633
TI  - Peripheral nerve regeneration across 14-mm gaps: a comparison of autograft and
      entubulation repair methods in the rat.
AB  - A study was conducted to compare the regeneration across 1.4-cm peroneal nerve
      gaps in rats, repaired with sutured autografts or with artificial nerve grafts.
      The artificial models were composed of a biodegradable passive conduit made of
      glycolide trimethylene carbonate, filled with either phosphate-buffered saline or
      a collagen extracellular matrix. Functional recovery was evaluated by walking
      track analysis throughout the experiment. After 9 months, the nerves were
      analyzed by electrophysiology and by qualitative and quantitative histology.
      Walking track analysis demonstrated the three repair methods to provide
      statistically equivalent recovery, except at day 195 post-engraftment, when the
      collagen-filled conduit was superior to the saline-filled conduit.
      Electrophysiologically, the autograft was superior to the collagen-filled
      conduit, while the collagen- and saline-filled conduits were equivalent.
      Quantitative histology demonstrated that normal intact nerve had larger mean
      myelinated axonal diameters but an equal number of axons to the three repair
      methods, and that the repair methods were statistically equivalent. While the
      repair methods had similar histologic and functional outcomes, combined
      standardized scoring demonstrated that the autograft was superior to the
      statistically-equivalent entubulation repairs. A collagen gel may serve as an
      ideal matrix in which to suspend neurotrop(h)ic factors or cells.

PMID- 8301634
TI  - Effects of lidocaine and calcitonin gene-related peptide (CGRP) on isolated human
      radial arteries.
AB  - Vasoconstriction during and after microsurgery may cause hypoperfusion and result
      in flap necrosis. This study investigated the vascular effects of two known
      vasodilators: lidocaine and the naturally-occurring substance, calcitonin gene
      related peptide (CGRP). Experiments were performed in vitro on 47 human radial
      arterial rings from 18 patients undergoing reconstruction after head and neck
      tumor surgery with free radial forearm flaps. Lidocaine produced a biphasic dose
      response curve, with contraction at low concentrations (1.5 x 10(-5) to 1.5 x 10(
      3) M) and relaxation at higher concentrations (4.5 x 10(-3) to 1.5 x 10(-2) M).
      It caused significantly stronger contractions in arteries with mechanically
      removed endothelium, compared with arteries with intact endothelium. Prolonged
      rebound contraction occurred when the lidocaine concentration was decreased.
      Lidocaine also potentiated noradrenaline-induced contraction. CGRP produced only
      dose-dependent relaxation of constricted radial arteries at low concentrations (3
      x 10(-10) to 10(-7) M). The contractile effects of lidocaine should be considered
      when a vasodilative substance is required.

PMID- 8301635
TI  - A comparison of immune response to nerve and skin allografts.
AB  - Research in limb reconstruction using peripheral nerve tissue has been hampered
      by tissue rejection. Not all tissues express major histocompatibility class I and
      class II antigens to the same extent. Allogenic and isogenic peripheral nerve
      grafts and split-thickness skin grafts were performed using C57BL/6 and Balb/c
      mice, which are inbred strains that differ at both major histocompatibility (MHC)
      class I and class II antigens. The cellular and humoral immune responses of the
      nerve transplants were compared with studies of skin transplants. Skin allografts
      represent a "gold standard": they are clearly rejected, with a tissue failure
      that is easily observed and closely correlated with cellular and humoral
      projection responses. A significant cellular immune response was noted following
      both the nerve (p < .04) and skin (p < .03) allografts. The peak response
      occurred by day 14 following the transplantation. The humoral response with
      rising antibody titers followed a similar pattern, with peak response at 14 and
      21 days post-transplantation. Isogenic transplants did not produce a cellular or
      humoral immune responses. There was no significant difference between the immune
      responses produced by the skin transplants, compared to the nerve transplants.
      Because of the difficulty in producing accurate models of animal function
      following nerve transplantation, quantitative studies of host immune response to
      transplantation have not correlated well with the recipient's final functional
      result. A comparison of the immune responses between clearly rejected skin
      allografts and nerve allografts suggests that the immune response resulting from
      nerve allografts could decrease the functional performance of the nerve
      grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301636
TI  - Experimental study of prefabricated flaps using vein grafts.
AB  - Prefabrication of a flap may represent a new alternative, not limited by natural
      vascular territories, for creating donor sites. Experimental procedures in which
      an A-V shunt results in sufficient flap neovascularization have been reported.
      This study was undertaken to investigate how neovascularization from the
      recipient bed affects survival of this type of flap. An 8-cm x 10-cm
      prefabricated skin flap, nourished by the left epigastric vein, was constructed
      in a rabbit abdomen. In half the models, a silicone sheet was placed under the
      flap, to impede neovascularization from the bed. The flaps of both experimental
      groups showed excellent viability, and no statistically significant difference in
      survival rate was recognized. This flap was found to be independent of the
      vascularity of the underlying bed.

PMID- 8301637
TI  - A simple arteriotomy method for microsurgical end-to-side anastomoses: technical
      aspects of use in training and laboratory applications.
AB  - An experiment was carried out to show the patency rates of microsurgical carotid
      artery bypasses with femoral artery grafts, using a single-cut arteriotomy in
      rats. A bypass was done on 127 Sprague-Dawley rats. Of these, 125 were patent
      after 20 min, and all of these were patent after the animals were sacrificed at 3
      days, for a 98 percent patency rate. The method of performing the arteriotomies,
      as well as the bypass itself, is described. The benefits of using the end-to-side
      anastomosis are explained. The authors conclude that the single-cut arteriotomy
      is convenient and easy to perform. The end-to-side anastomosis is a worthwhile
      technique and should encourage the proficiency of every student of microsurgery.

PMID- 8301638
TI  - Can genetic markers contribute to the classification of juvenile rheumatoid
      arthritis?

PMID- 8301639
TI  - What's in a name: the nomenclature of juvenile arthritis.

PMID- 8301640
TI  - What's in a name? Nomenclature of juvenile arthritis. A North American view.

PMID- 8301641
TI  - What's in a name? Nomenclature of juvenile arthritis. A European view.

PMID- 8301642
TI  - The glucocerebrosidase locus in Gaucher's disease: molecular analysis of a
      lysosomal enzyme.

PMID- 8301643
TI  - Development and validation of laboratory procedures for preimplantation diagnosis
      of Duchenne muscular dystrophy.
AB  - In order to develop and validate methods for the preimplantation diagnosis of
      Duchenne muscular dystrophy (DMD), we have established and evaluated PCR assays
      for the analysis of four loci within the DMD gene and for two Y chromosome
      sequences in single cells. A model system using buccal cells picked from
      mouthwash samples has been used for an extensive evaluation of the sensitivity
      and specificity of the assays, and each assay has been tested in samples
      containing single cells, two cells, and three cells per tube. The four DMD and
      two Y assays have been combined in duplex and triplex reactions to enable
      simultaneous diagnosis of DMD and of fetal sex. One of the DMD markers is a
      highly polymorphic simple tandem repeat locus which produces a basic DNA profile,
      and provides a control for contamination by foreign DNA. Amplification of DMD or
      Y sequences was observed in 78 to 92% of single male cells, rising to 96% and 97%
      in tubes containing two or three male cells respectively. Coamplification of both
      a DMD and a Y sequence together occurred with a mean success of 74% in single
      male cells, increasing to 93% with two, and 95% with three cells per tube. With
      appropriate precautions, we believe that it is now possible to proceed to
      clinical application of these procedures.

PMID- 8301644
TI  - Evidence for genetic homogeneity in autosomal recessive generalised myotonia
      (Becker).
AB  - Generalised myotonia Becker (GM) is an autosomal recessively inherited muscle
      disorder. Affected subjects exhibit myotonic muscle stiffness in all skeletal
      muscles with marked hypertrophy in the legs. A transient muscle weakness is
      particularly pronounced in the arms and hands and is a typical symptom of the
      disorder. Recently, we showed complete linkage of the disorder GM to the gene
      (CLCN1) coding for the skeletal muscle chloride channel CLC-1 and the TCRB gene
      on chromosome 7 in German families. In the study presented here we performed
      linkage analysis on 14 new GM families. The GM locus was again completely linked
      to both the CLCN1 and the TCRB gene in all families with a combined lod score of
      Z = 9.26 at a recombination fraction of theta = 0.00. This confirms our previous
      data and supports the hypothesis that GM is a genetically homogeneous disorder.
      The previously detected T to G missense mutation is found on 15% of the 66 GM
      chromosomes counted so far.

PMID- 8301646
TI  - Genetic mapping of the Kallmann syndrome and X linked ocular albinism gene loci.
AB  - The X linked form of Kallmann syndrome (KAL) and X linked ocular albinism (OA1)
      have both been mapped to Xp22.3. We have used a dinucleotide repeat polymorphism
      at the Kallmann locus to type 17 X linked ocular albinism families which had
      previously been typed for the Xg blood group (XG) and the DNA markers DXS237
      (GMGX9), DXS143 (dic56), and DXS85 (782). Close linkage was found between KAL and
      OA1 with a maximum lod score (Zmax) of 30.14 at a recombination fraction (theta
      max) of 0.06 (confidence interval for theta: 0.03-0.10). KAL was also closely
      linked to DXS237 (Zmax = 15.32; theta max = 0.05; CI 0.02-0.12) and DXS143 (Zmax
      = 14.57; theta max = 0.05; CI 0.02-0.13). There was looser linkage to the Xg
      blood group (XG) and to DXS85 (782). Multipoint linkage analysis gave the map:
      Xpter-XG-0.13-DXS237-0.025-KAL-0.025-DXS143-0.01 5-OA1-0.09-DXS85-Xcen. Placement
      of OA1 proximal to DXS143 was supported by odds of 2300:1 compared to other
      orders. This confirms our previous localisation of OA1 and improves the genetic
      mapping of both disease loci.

PMID- 8301645
TI  - Chromosomal localisation of a gene(s) for Turner stigmata on Yp.
AB  - Although recent cytogenetic and molecular studies in patients with Turner
      stigmata are consistent with a gene(s) for Turner stigmata being present on both
      Xp and Yp, the precise location has not been determined. In this report, we
      describe a phenotypically female infant with Turner stigmata and a partial Yp
      deletion and review genotype-phenotype correlations of the putative Turner
      gene(s) in non-mosaic patients with Y chromosome rearrangements resulting from
      chromosomal breakage at Yp or Yc (pericentromeric region). The results indicate
      that the putative Turner gene(s) on Yp is located in the Y specific region from
      interval 1A1A to interval 2B. In addition, assessment of ZFX/ZFY and RPS4X/RPS4Y
      in the context of the Turner gene(s) suggests that ZFX/ZFY rather than
      RPS4X/RPS4Y could be a candidate gene for the Turner stigmata.

PMID- 8301647
TI  - Types, stability, and phenotypic consequences of chromosome rearrangements
      leading to interstitial telomeric sequences.
AB  - Using in situ hybridisation, we identified interstitial telomeric sequences in
      seven chromosomal translocations present in normal and in syndromic subjects.
      Telomeric sequences were also found at the centromeric ends of a 4p and a 4q
      caused by centric fission of one chromosome 4. We found that rearrangements
      leading to interstitial telomeric sequences were of three types: (1) termino
      terminal rearrangements with fusion of the telomeres of two chromosomes, of which
      we report one case; (2) rearrangements in which an acentric fragment of one
      chromosome fuses to the telomere of another chromosome. We describe four cases of
      Prader-Willi syndrome with the 15q1-qter transposed to the telomeric repeats of
      different recipient chromosomes; (3) telomere-centromere rearrangements in which
      telomeric sequences of one chromosome fuse with the centromere of another
      chromosome. We describe two examples of these rearrangements in which not only
      telomeric sequences but also remnants of alphoid sequences were found at the
      fusion point. Instability at the fusion point of the derivative chromosome was
      found in the Prader-Willi translocations but we were unable to correlate this
      instability with culture conditions. The two subjects with the termino-terminal
      rearrangement and the centric fission respectively have normal phenotypes. The
      two patients with telomere-centromere fusions were unbalanced for the short arm
      of an acrocentric chromosome and had failure to thrive; one of them also had
      dysmorphic facies. We postulate that these phenotypes could be the result of
      uniparental disomy.

PMID- 8301648
TI  - Diagnostic criteria and genetics of the PEHO syndrome.
AB  - The PEHO syndrome (progressive encephalopathy with oedema, hypsarrhythmia, and
      optic atrophy) is a recently recognised disorder of unknown biochemical
      background. Diagnostic features have been found in neuroradiological and
      neuropathological studies, which show characteristic severe cerebellar atrophy.
      In combined neuroradiological and ophthalmological studies, 10 out of 21 possible
      PEHO patients fulfilled the criteria for true PEHO syndrome. All were abnormal at
      birth showing hypotonia, drowsiness, or poor feeding. Head circumference was
      normal, but usually dropped to 2 SD below average during the first year of life.
      Visual fixation was either absent from birth or lost during the first months of
      life. Nine patients had peripheral oedema in early childhood. The mean age of
      onset of infantile spasms was 4.9 months. All patients were extremely hypotonic
      and no motor milestones were reached. Patellar reflexes were brisk. Brain stem
      and somatosensory evoked potentials were abnormal in each case studied, cortical
      responses of somatosensory evoked potentials could not be elicited, and motor
      conduction velocities became delayed with age. Altogether 19 PEHO patients were
      found in 14 Finnish families. Autosomal recessive inheritance is likely.

PMID- 8301650
TI  - Neural tube defects: a survey of lesion descriptions made by different European
      pathologists.
AB  - Recent epidemiological interest has focused on separation of neural tube defects
      (NTD) into subgroups which may differ pathogenetically and aetiologically, for
      example, 'upper' and 'lower' spina bifida. In order to validate the use of
      pathologists' lesion descriptions by epidemiologists and others, a postal survey
      of 18 European perinatal pathologists, identified by EUROCAT registries, was
      conducted. Pathologists were asked, anonymously, to describe and identify the
      lesions in 15 photographs of midtrimester termination fetuses. There was a 50%
      response rate. Even taking into consideration the limitations of dealing with
      photographs rather than the fetuses themselves, there was often marked variation
      in the descriptions. Standardisation of terminology and international consensus
      about the type of detail recorded for NTD are urgently needed.

PMID- 8301649
TI  - Lethal short rib-polydactyly syndromes: further evidence for their overlapping in
      a continuous spectrum.
AB  - We report two new unrelated infants with short rib-polydactyly syndrome (SRPS)
      whose clinical and radiological features overlap the four established forms of
      lethal SRPS, so that it is difficult to classify them into any one particular
      type. One of the babies had one of the most radiologically severe SRPS ever
      published. The patients presented here support the previously reported hypothesis
      that this group of disorders might be a continuous spectrum rather than separate
      entities.

PMID- 8301651
TI  - Evidence of genetic and phenotypic heterogeneity in the Romano-Ward syndrome.
AB  - We report two families with phenotypically different forms of Romano-Ward
      syndrome. In one family, only five of 18 affected subjects are symptomatic,
      whereas in the other the proportion is three out of five. The families show
      distinct ECG morphologies, in addition to QT prolongation. Previous reports have
      shown genetic linkage either to the HLA locus on chromosome 6 or the Harvey-ras
      oncogene on chromosome 11. No linkage was found to either locus in the families
      reported here. The implications of phenotypic and genotypic heterogeneity in
      Romano-Ward syndrome are discussed in relation to the neurogenic and intrinsic
      models of pathogenesis.

PMID- 8301652
TI  - Non-isotopic analysis of single strand conformation polymorphism (SSCP) in the
      exon 13 region of the human dystrophin gene.
AB  - More than 30% of Duchenne and Becker muscular dystrophy (DMD/BMD) patients have
      no gross DNA rearrangements like deletions or duplications. The large size of the
      coding sequence of the dystrophin gene (11 kilobases) complicates systematic
      identification of point mutations. Recently reported approaches based on genomic
      DNA or mRNA show that chemical cleavage of mismatches is an effective but time
      consuming and technically demanding method for the identification of point
      mutations in the human dystrophin gene. We have used a fast and convenient system
      consisting of PCR amplification of genomic DNA, non-isotopic SSCP analysis, and
      direct sequencing of PCR products for the detection of mutations in exon 13 and
      adjacent intron sequences. Sixty-eight DMD patients without detectable deletions
      or duplications were analysed, resulting in the identification of a point
      mutation in the coding sequence and two polymorphisms in the 5' flanking intron.
      The C to T change of the first nucleotide in the third triplet leads to a stop
      codon and seems to be the cause of the functional deficiency of the gene product
      in this patient.

PMID- 8301654
TI  - Sex dependent transmission of Beckwith-Wiedemann syndrome associated with a
      reciprocal translocation t(9;11)(p11.2;p15.5).
AB  - Beckwith-Wiedemann syndrome (BWS), a disorder associated with neonatal
      hypoglycaemia, increased growth potential, and predisposition to Wilms's tumour
      (WT) and other malignancies, has been mapped to 11p15. The association with 11p15
      duplications of paternal origin, of balanced translocations and inversions with
      breakpoints within 11p15.4-p15.5 of maternal origin, and the demonstration of
      uniparental paternal 11p15 isodisomy in some sporadic cases point towards the
      involvement of genomic imprinting. In agreement with this, we show the paternal
      origin of a de novo 9;11 translocation in a phenotypically normal mother, whose
      carrier daughter developed BWS. This supports the fact that BWS associated with
      balanced chromosome mutations is transmitted in the same sex dependent pattern as
      non-cytogenetic forms of familial BWS.

PMID- 8301653
TI  - Dystrophin analysis in idiopathic dilated cardiomyopathy.
AB  - Idiopathic dilated cardiomyopathy (DCM) is characterised by ventricular
      dilatation and impaired systolic function resulting in congestive heart failure
      and frequently death. A dilated cardiomyopathy is common in patients with
      symptomatic Duchenne/Becker muscular dystrophy, a disease caused by dystrophin
      gene defects. However, cardiomyopathy is rarely the predominant clinical feature
      of this form of muscular dystrophy. To determine whether dystrophin gene defects
      might account for a significant number of patients with apparently isolated
      idiopathic DCM, we performed dystrophin gene analysis in 27 DCM patients, who
      were ascertained as part of a prospective study on idiopathic DCM. No dystrophin
      gene defects were found in our patients, whose average age was 50 years. These
      data suggest that dystrophin defects are not a common cause of idiopathic DCM in
      this age group in the absence of skeletal muscle cramps or weakness.

PMID- 8301655
TI  - Epidermal naevi and bullous aplasia cutis congenita in a neonate.
AB  - The case of a neonate with cutaneous lesions consistent with epidermal naevi is
      presented. In addition to typical epidermal naevi, this baby had an unusual,
      bullous form of aplasia cutis congenita. Although aplasia cutis has been
      described as bullous and has been found in association with the epidermal naevus
      syndrome, both of these occurrences are rare in medical publications. This case
      illustrates an unusual presentation of epidermal naevi with bullous aplasia cutis
      congenita and raises difficult diagnostic and counselling issues.

PMID- 8301656
TI  - Transmission of a ring chromosome 18 from a mother with 46,XX/47,XX, + r(18)
      mosaicism to her daughter, resulting in a 46,XX,r(18) karyotype.
AB  - A 6 month old patient is reported with a ring chromosome 18 confirmed by
      cytogenetic studies and in situ hybridisation. Her clinical features were similar
      to previous cases of ring chromosome 18 syndrome. The ring chromosome was
      inherited from the phenotypically and mentally normal mother with a mos
      46,XX/47,XX, + r(18) karyotype.

PMID- 8301657
TI  - 46,XX/69,XXX diploid-triploid mixoploidy with hypothyroidism and precocious
      puberty.
AB  - We report a 20 month old female patient with diploid-triploid mixoploidy
      (46,XX/69,XXX) syndrome with hypothyroidism and precocious puberty. The triploid
      cell line was only expressed in the fibroblast culture and comprised the majority
      (95%) of the cells. Chromosome analysis of the fetal blood sample and peripheral
      blood sample were normal. The patient shows typical features of full triploidy
      (growth and severe mental retardation, cranial and facial dysmorphism, complete
      syndactyly of fingers 3/4, partial syndactyly of toes 2/3) and facial but no body
      asymmetry. At the age of 5 months central hypothyroidism and precocious puberty
      were diagnosed. Thin pigmented streaks were visible on the wrists and legs of the
      patient at the age of 16 months. This is the first patient reported so far with
      46,XX/69,XXX mixoploidy suffering from hypothyroidism and precocious puberty.

PMID- 8301658
TI  - X linked recessive thrombocytopenia.
AB  - A Saudi Arab boy presented in early childhood with thrombocytopenia,
      morphologically large and normal sized platelets, increased mean platelet volume,
      and a hypermegakaryocytic bone marrow. There was no clinical and laboratory
      evidence of any significant immunological abnormalities. Similar findings in two
      other brothers suggested strongly that they were all suffering from an X linked
      recessive thrombocytopenic disorder. Results of DNA analysis with the probe M27
      beta are consistent with X linkage and indicate also that the locus of the
      relevant gene lies close to or is identical to the locus of the gene for the
      Wiskott-Aldrich syndrome (WAS). Because of various features which include the
      presence of large and normal sized platelets (rather than small platelets) and
      freedom from significant immune deficiencies, it is likely that the X linked
      recessive thrombocytopenia in this family is an isolated entity quite distinct
      from the classical WAS phenotype. However, a modified expression of the WAS gene
      producing a mild phenotypic variant cannot be excluded entirely.

PMID- 8301659
TI  - Pseudotrisomy 13 and autosomal recessive holoprosencephaly.
AB  - Two sibs, diagnosed prenatally, had holoprosencephaly, midface hypoplasia, and
      normal chromosomes. The first fetus also had polydactyly. This sibship may
      represent an example of autosomal recessive pseudotrisomy 13.

PMID- 8301660
TI  - A report on CF carrier frequency among men with infertility owing to congenital
      absence of the vas deferens.

PMID- 8301662
TI  - Vertical integration, clinic without walls, physician-hospital organizations:
      what it means and is it right for you?

PMID- 8301661
TI  - Skeletal malformations and polycystic kidney disease.

PMID- 8301663
TI  - A house that "love built".

PMID- 8301664
TI  - The autonomic nervous system, myocardial infarct size and ventricular
      fibrillation.

PMID- 8301665
TI  - Evidence that myocardial pertussis toxin substrates are uniquely altered in acute
      murine Chagas' disease in a manner unrelated to myocardial dysfunction.
AB  - In an effort to correlate biochemical characteristics of the beta-adrenergic
      receptor complex with myocardial function, mouse myocardial GTP-binding proteins,
      specifically substrates for pertussis toxin (PT), were analysed with regard to
      the influence of infection with Trypanosoma cruzi, the causative agent of Chagas'
      cardiomyopathy. Infection was found to decrease in a non-uniform manner the
      magnitude of ADP-ribosylation in the PT substrates. High detergent concentrations
      attenuated the infection-associated decrease in PT-dependent ADP-ribosylation.
      Infection also altered the kinetics of the PT-dependent ADP-ribosylation reaction
      from a time course wherein maximal PT-dependent ADP-ribosylation occurred after
      12 h incubation in control animals to one in which maximal PT-dependent ADP
      ribosylation occurred after 3 h incubation and thereafter declined.
      Immunochemical analysis of the PT-substrates revealed an infection-associated
      decrease in alpha i1, alpha o, an increase in alpha i2 and no change in alpha i3.
      Verapamil treatment, which prevents the clinical consequences of infection, did
      not influence any of the infection-associated changes in PT-dependent ADP
      ribosylation of GTP-binding protein substrates or their immunochemical
      properties. Complementary studies using isolated rat neonatal cardiocytes
      infected with the parasite further substantiated the finding that the infection
      associated decrease in PT-dependent ADP-ribosylation and the associated change in
      the kinetics of the reaction were properties uniquely associated with the
      presence of the parasite.

PMID- 8301666
TI  - Atrial natriuretic factor blocks the high-threshold Ca2+ current and increases K+
      current in fetal single ventricular cells.
AB  - The effect of atriopeptin III (ANF) was studied on K+, Ca2+ and Na+ currents of
      single heart cells of 10-day-old chick embryos and 17- to 20-week old human
      fetuses. ANF III (2 x 10(-9) M) greatly decreased the basal and cAMP
      prestimulated high-threshold (IL) Ca2+ current without affecting the low
      threshold Ca2+ current (IT) or the TTX-sensitive fast inward Na+ current. ANF III
      was also found to increase the delayed outward K+ currents (IK) in a dose
      dependent fashion (10(-10) to 10(-7) M). The effects of ANF III on IK and IL were
      reversible upon washout of this hormone. Increasing intracellular guanosine 3',5'
      cyclic monophosphate (cGMP) blocked IL but had no effect on IK. These results
      suggested that ANF regulated one type of Ca2+ current and the delayed outward K+
      current in single heart cells. The effects of ANF on IL (but not on IK) could be
      due in part to the increased [cGMP]i levels or to an unknown signal transduction
      that is stimulated by this hormone.

PMID- 8301667
TI  - Role of calcium current and sarcoplasmic reticulum calcium release in control of
      myocardial contraction in rat and rabbit myocytes.
AB  - The relative importance of calcium current and sarcoplasmic reticulum in
      supplying contraction-related calcium was investigated in isolated rat and rabbit
      cardiac ventricular myocytes using patch-clamp and video techniques. Calcium
      current and contractile response were manipulated via variation of [Ca2+]o
      between 0.25 and 8.0 mM. Sarcolemmal calcium influx was derived from integration
      of the calcium current. An increase in [Ca2+]o from 0.25 to 8 mM augmented the
      amplitude of contractile shortening from 7 to 375% of control (amplitude at 1.0
      mM) in rat but only from 36.5 to 177.6% in rabbit. Upon variation in [Ca2+]o from
      0.5 to 8.0 mM calcium current increased from 67 to 175% of control in rat and
      from 65 to 150% in rabbit. Sarcolemmal calcium influx in rat was, however, only
      about half of that in rabbit for the entire range of [Ca2+]o and saturated at
      [Ca2+]o over 2.0 mM in both species. Application of 1 microM ryanodine increased
      calcium current and slowed its inactivation time course in the rat, but in the
      rabbit a slight decrease in current was observed and the inactivation time course
      was not obviously affected. The sarcoplasmic reticulum calcium
      release:transsarcolemmal calcium flux ratio is at least four-fold greater in the
      rat than in the rabbit. The results from this study further explain the well
      known marked differences in contractile control in the two species.

PMID- 8301668
TI  - Intracellular Ca2+, force and activation heat in rabbit papillary muscle: effects
      of 2,3-butanedione monoxime.
AB  - We have investigated the effects of 2,3-butanedione monoxime (BDM) and mannitol
      on Ca2+ metabolism in rabbit cardiac muscle. Simultaneous measurements of force
      and intracellular Ca2+ were made in right ventricular papillary muscles loaded
      with the fluorescent Ca2+ indicator fura-2. At a BDM concentration of 2 mM, peak
      isometric force was only 52% of control values and this was reduced to 18% at a
      concentration of 5 mM. The peak of the Ca2+ transient decreased by 8% at 2 mM BDM
      and by 18% at the higher concentration. In the presence of 362 mM mannitol peak
      isometric force decreased by 78% and there was a tendency for the peak of the
      Ca2+ transient to increase. A combination of 362 mM mannitol with 5 mM BDM
      completely inhibited force production despite peak Ca2+ levels that were no
      different from control values. In myothermic experiments under similar conditions
      the latency release protocol of Gibbs et al. (1988) and the BDM protocol of
      Alpert et al. (1989) were used to derive independent estimates of tension
      independent (activation) heat in the same muscle. For both protocols the heat
      stress relationship was well fitted by first-order linear regression. The
      activation heat estimate was significantly higher when measured with the latency
      release technique (2.31 mJ/g) compared with the BDM protocol (1.24 mJ/g). Our
      results confirm that in rabbit cardiac muscle low concentrations of BDM (2 mM)
      cause a marked inhibition of force development with little apparent effect on
      peak Ca2+ levels. Therefore, the lower activation heat estimates under these
      conditions may not be due to a reduced intracellular Ca2+ concentration. It is
      possible that the higher activation heat values obtained with protocols not
      involving chemical interventions may include the energy usage contributed by
      cellular processes that presumably do not occur in the presence of BDM and
      mannitol.

PMID- 8301669
TI  - Angiotensin II receptor subtypes and biological responses in the rat heart.
AB  - The distribution and function of AII receptor subtypes was evaluated in different
      preparations of rat hearts. Autoradiographic experiments and binding experiments
      on isolated membranes showed a large expression of [125I]Sar1,Ile8-AII binding
      sites in the atria of neonatal Wistar Kyoto rats which were predominantly of the
      AT2 subtype. Atrial and ventricular cells, isolated from neonatal rat hearts and
      maintained for 3 days in culture demonstrated primarily AT1 binding sites.
      Stimulation of cultured atrial cells with AII resulted in an increase in inositol
      phosphate turnover and in intracellular calcium. The latter action was completely
      abolished by Losartan. Finally, in atria isolated from 2-month-old rats, AII
      produced a 17-19% increase in contractile force that was completely abolished by
      Losartan but not by PD 123319, thus indicating the presence of functional AT1
      receptors.

PMID- 8301670
TI  - Contribution of cardiac renin-angiotensin system to ventricular remodelling in
      myocardial-infarcted rats.
AB  - To investigate the contribution of the cardiac renin-angiotensin system to
      ventricular dilatation after myocardial infarction, we examined the effects of 3
      week treatments with an angiotensin converting enzyme inhibitor, delapril, and a
      selective angiotensin II type 1 (AT1) receptor antagonist, TCV-116, on
      haemodynamics and ventricular angiotensin II contents in myocardial-infarcted
      rats. TCV-116 reduced mean aortic pressure, and prevented the increase of right
      and left ventricular weight, left ventricular end-diastolic pressure and volume
      of myocardial-infarcted rats, to a similar extent to delapril. Thus, AT1 receptor
      mediated action of angiotensin II plays a central role in the development of
      ventricular dilatation. Angiotensin II contents in the right and non-infarcted
      left ventricles (6.0 +/- 1.0 and 5.9 +/- 0.7 pg/g tissue, respectively, mean +/-
      S.E.M.) of myocardial-infarcted rats were not different from those of sham
      operated rats. However, angiotensin II contents in the infarcted scar (21.7 +/-
      3.5 pg/g) of myocardial-infarcted rats were 4.2-fold higher than those in the
      left ventricle of sham-operated rats. Delapril reduced angiotensin II contents in
      the right and non-infarcted left ventricles, and the scar by 48, 81 and 60%,
      respectively, but did not reduce plasma angiotensin II in myocardial-infarcted
      rats. TCV-116 also decreased angiotensin II in the right and non-infarcted left
      ventricles by 57 and 56%, respectively, while increased plasma angiotensin II by
      4.3-fold. Thus, the prevention of ventricular dilatation by these two agents was
      associated with the decrease in ventricular angiotensin II contents. These
      observations suggest that the cardiac renin-angiotensin system rather than the
      circulating system may play an important role in ventricular dilatation after
      myocardial infarction.

PMID- 8301671
TI  - Summer infections: where do they come from?

PMID- 8301672
TI  - Cataract in adults: management of functional impairment--a patient's guide. US
      Department of Health and Human Services, Public Health Service, Agency for Health
      Care Policy and Research.
AB  - 1. A regular eye exam is all that is needed to find a cataract. 2. A cataract
      does not have to be removed right away. 3. Talk with your doctor about how your
      cataract affects your vision and your life. 4. After talking with your doctor,
      decide whether surgery is right for you.

PMID- 8301673
TI  - Ocular fixation using a baseball catcher's mask for postoperative prone
      positioning.
AB  - 1. The optimal ocular position after vitreoretinal surgery with intravitreous gas
      tamponade is with the axis of the eye pointed downward. 2. Careless prone
      fixation may cause accidents of eyeball depression. 3. To help patients keep the
      proper prone facial and ocular positions, a modified catcher's mask was developed
      for use as a facial support.

PMID- 8301674
TI  - Refractive errors and automated perimetry: discussion and case studies.
AB  - 1. The effects of refractive error on automated perimetry were studied. The
      results of the study showed that an error of as little as 1 diopter can
      significantly influence the visual field to as much as 30 degrees from fixation.
      2. In the case of automated visual field testing when only the central 30 degrees
      of visual field are tested, refractive error can cause a generalized depression.
      Because generalized depression can have several different causes, distinguishing
      between a true depression and one due to refractive error can be important. 3.
      Because a generalized depression from refractive error can mimic a depression due
      to true pathology, it is critical that the most recent refraction combined with
      the correct add for perimetry be used on each patient every time the patient
      undergoes a visual field examination.

PMID- 8301675
TI  - Multifocal intraocular lens technology and clinical applications.
AB  - 1. Some of the newest intraocular lens (IOL) implant technology involves a
      diffractive multifocal IOL. 2. Sixty-three percent of multifocal IOL cases need
      to spectacle correction. 3. Patients must have realistic expectations. They
      should have a desire for reduced dependency on eye glasses.

PMID- 8301676
TI  - Ocular toxoplasmosis.
AB  - 1. Women with no immunity to Toxoplasma organisms acquire toxoplasmosis during
      pregnancy; the infection spreads to the fetus by transplacental transmission. 2.
      Blurred vision, floaters, photopsia, pain, and redness are common complaints of
      the active retinochoroiditis. 3. The diagnosis of ocular toxoplasmosis can be
      confirmed by blood tests, the most common being the indirect fluorescent antibody
      (IFA) and the enzyme-linked immunosorbent assay (ELISA).

PMID- 8301677
TI  - The parents of a 9-month-old black girl discovered a yellow pupil in her right
      eye. Retinoblastoma.

PMID- 8301678
TI  - Dealing with the dry-eyed patient.

PMID- 8301679
TI  - Hidden sugars.

PMID- 8301680
TI  - Ocular manifestations in bone marrow transplantation.
AB  - 1. Primary and relapsed acute leukemia is increasingly being treated by bone
      marrow transplantation. Graft-versus-host disease (GVHD) is a major complication
      of bone marrow transplantation, occurring in 50% to 70% of cases. 2. Ocular
      complications of bone marrow transplantation are divided in those involving
      either the anterior or posterior segment. Because of associated total body
      irradiation with different forms of chemotherapy, these patients should be
      routinely watched by an ophthalmologist. 3. There is a high incidence of dry eye
      syndrome, viral keratitis, and trophic disturbances of the cornea. The presence
      of GVHD increases ocular involvement and its severity. 4. A study by Lopez and
      colleagues indicated that 62% of patients who survived at least 6 months after
      bone marrow transplantation for acute leukemia developed occlusive microvascular
      retinopathy.

PMID- 8301681
TI  - Follow-up of day-surgery cataract patients.
AB  - 1. Cataract patients received widely differing amounts of information about their
      surgery and their pre- and postoperative courses. Although most received some
      information, no patient received what could be considered complete information.
      2. Most patients would have liked more specific information about what they could
      expect and what they could do to take care of themselves after surgery. Some
      patients were surprised that they could not see perfectly after surgery. Such
      feelings led to uncertainty and concern about the success of the procedure. 3.
      The cataract patients had a relatively uneventful postoperative course,
      complaining little about nausea, vomiting, fatigue, and difficulty moving and
      sleeping. Although pain generally was rated as low, 15% of patients complained of
      severe pain on the 1st postoperative day.

PMID- 8301682
TI  - Eradication of vitamin A deficiency with 5 cents and a vegetable garden.
AB  - 1. It is estimated that 10 million children are vitamin A deficient. Of these
      children, over 1 million needlessly die, go blind, or suffer lesser degrees of
      visual impairment every year. This problem--along with all forms of malnutrition-
      is likely to be seriously magnified by the year 2000. The scope of the problem is
      immense, and the need to address it is urgent. 2. Interventions for the
      prevention of vitamin A deficiency and its consequences are considered to be some
      of the most cost-effective and health-productive in the Third World--and yet the
      problem remains immense, representing one of the greatest failures in global
      public health planning. 3. As ophthalmic professionals, we are at the center of
      this urgent public health concern. We have an important responsibility in the
      initiation and development of sustainable programs for health promotion and
      disease prevention.

PMID- 8301683
TI  - Unusual ocular manifestation: ophthalmomyiasis.
AB  - 1. Ocular myiasis is an extremely rare condition. 2. Clinical features depend on
      the location of the larvae: ophthalmomyiasis anterior produces an exudative
      iridocyclitis; ophthalmomyiasis posterior results in a violent exudative
      posterior uveitis. 3. Visual prognosis for this condition is extremely poor.

PMID- 8301684
TI  - Troubleshooting ophthalmic nursing problems in the geriatric clinic population.
AB  - 1. Future problems of the ophthalmic geriatric patient may be avoided by
      including in the complete history all medical problems, medications, as well as
      present and past ocular conditions. 2. Each visit should include corrected and
      uncorrected visual acuity, both distance and near and pinhole when indicated.
      Tonometry also should be included. 3. Producing reliable visual fields requires
      time and patient teaching. 4. Family and friends can be helpful in the care of
      the eye patient and become an important part of their postoperative care.

PMID- 8301685
TI  - A salmon-colored mass seen subconjunctivally on the left eye. Lymphoma.

PMID- 8301686
TI  - Aspherics come of age.

PMID- 8301687
TI  - Progression and prognosis of destructive periodontal disease.

PMID- 8301688
TI  - Guided tissue regeneration and the role of the integrin family of cell surface
      adhesion receptors.

PMID- 8301689
TI  - How much should you pay your hygienist? How does the American scene apply to New
      Zealand?

PMID- 8301690
TI  - The diagnosis and management of oral-facial allergic responses in clinical
      practice.

PMID- 8301691
TI  - Melkersson-Rosenthal syndrome oro-facial granulomatosis.

PMID- 8301692
TI  - Oral squamous cell carcinoma.

PMID- 8301693
TI  - Two cases of herpes simplex infection.

PMID- 8301694
TI  - Guidelines for employing a hygienist in practice. Department of Periodontology,
      School of Dentistry, University of Otago.

PMID- 8301695
TI  - Significant demise of plaque and smoking in the Republic of Vanuatu.

PMID- 8301696
TI  - Aluminum chelation: chemistry, clinical, and experimental studies and the search
      for alternatives to desferrioxamine.
AB  - This review focuses on aluminum (Al) chelation, its chemistry and biology. The
      toxicology and biology of Al in mammalian organisms are briefly reviewed to
      introduce the problems associated with excessive Al exposure and accumulation and
      the challenges facing an effective Al chelator. The basics of Al chelation
      chemistry are considered to help the reader understand the Al chelation chemical
      literature. The chemical properties of Al enable prediction of effective
      functional groups for Al chelation. A compilation of distribution coefficients
      between octanol and aqueous phases (Do/a) for chelators and their complexes with
      Al shows the effect of complexation on lipophilicity. A compilation of stability
      constants for Al.chelator complexes illustrates the role of oxygen in ligands
      that form stable complexes. The history of clinical Al chelation therapy is
      reviewed, with emphasis on desferrioxamine (DFO), which has been extensively used
      since 1980. The beneficial and adverse effects and limitations of DFO use in end
      stage renal-diseased patients, in patients with neurodegenerative disorders,
      including Alzheimer's disease, and in animal models of Al intoxication are
      presented. The methods to evaluate potential Al chelators in vitro, in vivo, and
      using computer modeling are discussed. The Al chelation literature is reviewed by
      the chemical class of chelators, including fluoride, carboxylic acids, amino
      acids, catechols, polyamino carboxylic acids, phenyl carboxylic acids, the
      hydroxypyridinones, and hydroxamic acids.

PMID- 8301697
TI  - Inhibition of adenylate cyclase in perfusion mouse palate by secalonic acid D.
AB  - Glucocorticoids (GC) induce cleft palate (CP) in the offspring of exposed
      pregnant mice. Glucocorticoids induce prostaglandin (PG) synthesis inhibition via
      reduced arachidonic acid (AA) release from membranes, and this results from
      inhibition of phospholipase A2. This metabolic event is associated with reduced
      palatal cAMP levels in the prefusion stages (d 13 of gestation). The mycotoxin
      secalonic acid D (SAD) induces CP in the offspring born to treated mothers,
      elevates maternal plasma corticosterone levels, and reduces prefusion palatal
      cAMP levels. In addition, an increase in cAMP was noted in the postfusion period
      (d 15 of gestation). Since exogenous AA given simultaneously to GC-exposed
      mothers may protect against GC-induced CP in the offspring, such a possibility
      was tested for SAD. Pregnant CD1 mice given a teratogenic dose of SAD (30 mg/kg,
      ip, on gestational d 11) were simultaneously treated with maximal tolerated doses
      of AA (200 mg/kg, sc, on gestational d 11, 12, and 13). At term, no significant
      reduction in SAD-induced CP was seen as a result of AA treatment. To evaluate if
      SAD-induced alterations in palatal cAMP are due to reduced palatal membrane
      associated adenylate cyclase (AC) activity during pre- and postfusion periods,
      SAD-treated mothers were sacrificed at 12-h intervals between gestational d 13.5
      and 15.5, palate shelves were collected from the fetuses, and AC activity (cAMP
      formed/mg protein/min) was assayed in the presence or absence of the enzyme
      stimulator, sodium fluoride (NaF). Although SAD did not alter unstimulated AC
      activity, it significantly reduced the NaF-induced stimulation of enzyme activity
      in the prefusion period. This inhibition could not be reversed by excess GTP in
      the incubation mixture. Since NaF stimulation of AC indicates post-receptor-site
      function involving GTP-binding and catalytic units, and since addition of GTP
      failed to correct SAD-induced alteration of NaF stimulation of the enzyme, it is
      suggested that SAD may inhibit the AC sensitivity to stimuli by its effect on the
      catalytic unit in a manner that does not affect enzymic basal activity.

PMID- 8301698
TI  - Hyperthyroidism increases covalent binding and biliary excretion of 1,1
      dichloroethylene in rats.
AB  - Distribution, covalent binding, and biliary excretion of 1,1-dichloroethylene
      (DCE) were examined in euthyroid (EuT) and hyperthyroid (HyperT) rats, which are
      more vulnerable to DCE hepatotoxicity. Male Sprague-Dawley rats were made
      hyperthyroid by 3 sc injections of thyroxine at 48-h intervals prior to
      experiments; euthyroid controls received vehicle injections. A time course study
      monitored the circulation and excretion of 14C-DCE label for 24 h after
      administration of 14C-labeled DCE (50 mg/kg in mineral oil) in serial blood and
      urine samples. At 24 h, total and covalently bound 14C-label were measured in
      liver, kidney, and lung. Hepatotoxicity of DCE was enhanced in the HyperT rats,
      as evidenced by elevated serum activities of aminotransferase and histopathology,
      and was associated with increases in circulating metabolite, and in metabolite
      bound to red blood cells and liver but not to kidney or lung. Hyperthyroidism had
      little effect on in vitro capacity of hepatic microsomes to convert DCE to
      reactive intermediates as reflected by covalent binding. A biliary excretion
      study in pentobarbital-anesthetized rats showed a striking, but transient,
      increase in toxicant metabolite excretion in bile of HyperT rats during the first
      2 h after toxicant administration (14C-DCE, 100 mg/kg). During the next 2 h,
      biliary metabolite excretion by HyperT rats decreased while there was a rise in
      circulating amounts of total and bound 14C-label. Thus, although hyperthyroidism
      had little effect on the total extent of DCE metabolized, this hormonal
      disturbance may have transiently enhanced metabolite formation and definitely was
      associated with a lesser ability to detoxify reactive DCE metabolites capable of
      injuring hepatic cell constituents by covalent binding reactions.

PMID- 8301699
TI  - Heavy metals in avian eggshells: another excretion method.
AB  - Birds can rid their bodies of heavy metals through both excretion and deposition
      in feathers, and females can also eliminate heavy metals in the contents of their
      eggs. In this paper the levels of heavy metals (lead, cadmium, mercury, selenium,
      manganese, chromium) in the contents and shells of eggs of roseate terns (Sterna
      dougallii) and herring gulls (Larus argentatus) nesting at Cedar Beach, Long
      Island, are reported. For both species, metal concentrations were significantly
      higher in the contents compared to the shells for lead, mercury, selenium, and
      chromium. For herring gulls, metal levels were higher in the shells for cadmium
      and manganese. Levels of cadmium, mercury, and selenium were significantly higher
      in roseate tern egg contents than for herring gulls. In eggshells, lead, cadmium,
      mercury, and selenium were significantly higher in roseate terns compared to
      herring gulls. For both species, eggshells account for about 7-8% of the egg by
      weight, but less than 1% of the egg burden for mercury, 1-5% for lead, selenium,
      and chromium, and 7-11% for manganese. For cadmium, shells account for only 5% of
      the egg burden for roseate terns, but 29% for herring gulls. These data suggest
      that, except for mercury, eggshells provide another method of excretion of metals
      in these two species of birds.

PMID- 8301700
TI  - Concomitant exposure to carbon black particulates enhances ozone-induced lung
      inflammation and suppression of alveolar macrophage phagocytosis.
AB  - The goal of this study was to investigate whether coexposures to carbon black and
      O3 result in a toxicologic interaction in the lungs as quantitated by the
      inflammatory response and alveolar macrophage (AM) phagocytosis. This aim was
      accomplished through inhalation coexposures of Swiss mice for 4 h to target
      concentrations of 10 mg/m3 of carbon black and 1.5 ppm O3, or exposure to either
      agent alone. As a control for the coexposure experiments, mice were also exposed
      for 4 h to carbon black, followed immediately thereafter by exposure for 4 h to
      O3, or vice versa. At 24 h after exposure, the lungs of the animals were lavaged
      for quantitation of total and differential cell counts and assessment of AM Fc
      receptor-mediated phagocytosis. Exposure to carbon black did not result in an
      inflammatory response, nor had it any effect on AM phagocytosis. Ozone exposure
      resulted in an inflammatory response in the lungs and suppression of AM
      phagocytosis. Both biologic parameters were significantly enhanced following
      combined exposure to the particle and the gas. Carbon black exposure either
      before or after O3 had no significant effect on AM phagocytosis as compared to O3
      exposure alone. These data demonstrate the toxicologic interaction of coexposures
      to an inert particle and O3 on well-accepted biologic markers pulmonary toxicity.
      The mechanism for the enhanced biologic effect may be that the carbon black
      particle acts as a carrier mechanism for O3 to areas in the distal lung not
      accessible to O3 in the gaseous phase or that O3 alters the physicochemistry of
      the particulate from a nontoxic to a toxic form.

PMID- 8301701
TI  - Enhanced metallothionein gene expression is associated with protection from
      cadmium-induced genotoxicity in cultured rat liver cells.
AB  - Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins that
      appear to play an important role in the cellular defense system against cadmium
      toxicity. Although substantial evidence exists demonstrating a reduction in
      cadmium toxicity concomitant with MT induction, little is known about the
      possible effects of stimulation of MT synthesis on cadmium-induced genotoxicity.
      Thus, the alkaline elution technique was used to assess single-strand DNA damage
      (SSD) in TRL-1215 cells, a liver-derived cell line shown to have inducible MT
      gene expression. The SSD accumulated over a 2-h time period in a time-dependent
      manner following exposure to 500 microM CdCl2. Low-concentration cadmium
      pretreatment (10 microM CdCl2, 24 h) provided protection against the genotoxicity
      of high-concentration cadmium (500 microM CdCl2, 2 h). A 2-h exposure to 500
      microM CdCl2 had no effect on viability, as assessed using a tetrazolium-dye
      based assay, in cells from either the pretreated or nonpretreated group.
      Metallothionein was induced in a time-dependent manner by low-concentration
      cadmium pretreatment: Exposure for 24 and 48 h resulted in 3.3- and 6.4-fold
      increases, respectively. In addition, a 24-h exposure to low-concentration
      cadmium resulted in an increase in MT-I gene expression. Cadmium accumulation was
      2.6-fold greater in low-concentration cadmium-pretreated cells as compared to
      nonpretreated cells. These data demonstrate that low-concentration cadmium
      pretreatment provides protection against cadmium-induced single-strand DNA damage
      and support the hypothesis that this protection is due to stimulation of MT gene
      expression.

PMID- 8301702
TI  - Biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and
      biphenyls in double-crested cormorant chicks (Phalacrocorax auritus).
AB  - The present project assessed the effect of environmental contamination with
      polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls
      (PCBs) on hepatic microsomal ethoxyresorufin O-deethylase (EROD) activities and
      morphological parameters in matched double-crested cormorant (Phalacrocorax
      auritus) hatchlings from egg clutches chosen for chemical analysis. Double
      crested cormorant eggs were collected from five colonies across Canada, with
      differing levels of contamination. Levels of contamination expressed in sum of
      2,3,7,8-tetrachlorodibenzo-p-dioxin-toxic equivalents (TCDD-toxic equivalents or
      TEQ, ng/kg egg; mean +/- SEM) were: Saskatchewan, 250 +/- 50; Chain Islands, 672
      +/- 73; Christy Islet, 276 +/- 14; Crofton, 131, n = 1; and Lake Ontario, 1606 +/
      118. In the hatchlings, hepatic EROD activities (pmol/min/mg protein; mean +/-
      SEM) were: Saskatchewan, 283 +/- 42; Chain Islands, 516 +/- 98; Christy Islet,
      564 +/- 91; Crofton, 391 +/- 52; and Lake Ontario, 2250 +/- 156. Hepatic
      microsomal EROD activity (pmol/min/mg protein) regressed positively on TEQ (r2 =
      .69; p < .00005; n = 25). Yolk weight (g) regressed negatively on TEQ (r2 = .44;
      p = .00005). Wing length (mm) regressed negatively on PCB-169 (r2 = .28; p =
      .007). Monospecific antibodies raised against rat cytochrome P-450 1A1 recognized
      a protein in the hepatic microsomes of the double-crested cormorant, and also in
      those of the great blue heron (Ardea herodias), using immunoblotting. The
      intensity of the stained band increased with increased EROD activity, supporting
      the assumption that ethoxyresorufin is a suitable substrate for avian cytochrome
      P-450 1A1. These results validate the use of avian hepatic microsomal EROD
      activity as an index of cytochrome P-450 1A1 induction by environmental levels of
      polychlorinated aromatic hydrocarbons and as a useful screening tool to determine
      the extent of exposure to such chemicals. Furthermore, the induction of
      cytochrome P-450 1A1 observed in the cormorant indicates that the Ah receptor
      mediated process, by which TCDD and related chemicals exert many of their
      toxicities, has been activated.

PMID- 8301703
TI  - Comment on 'ventilation and blood lactate increase exponentially during
      incremental exercise'.
AB  - A recent paper in this journal has examined the ventilatory compensation for
      metabolic acidosis with increasing oxygen uptake, making extensive use of
      mathematical and statistical techniques. The authors conclude that
      '...respiratory compensation for metabolic acidosis during incremental exercise
      is a continuous process...'. While this may indeed be so, the following major
      aspects of the paper render the evidence at best dubious, surely inconclusive and
      perhaps even worthless: (1) The mathematical and statistical methodology is
      sloppy, incomplete and, at times, flawed. (2) No discontinuous model is presented
      for comparative purposes, only three continuous ones. (3) The authors ignore the
      fact that some threshold models produce smooth continuous data, and as a
      consequence, a good fit of a smooth continuous model cannot exclude the presence
      of a threshold. (4) The data in Table 5 show the amplitude parameter A of the
      preferred model to be not significantly different from zero. This paper draws
      these matters to the attention of readers of this journal, reviewers of
      manuscripts and other researchers, with comment and suggestion. This is done in
      the hope that all those concerned with mathematical and statistical methodologies
      will become more aware of their proper use.

PMID- 8301704
TI  - Electromyography and the study of sports movements: a review.
AB  - Within electromyography (EMG), a particular specialty has been developed wherein
      the aim is to use EMG for the study of muscular function and co-ordination. This
      area of research is usually called kinesiological EMG. The general aims of
      kinesiological EMG are to analyse the function and co-ordination of muscles in
      different movements and postures, in healthy subjects as well as in the disabled,
      in skilled actions as well as during training, in humans as well as in animals,
      under laboratory conditions as well as during daily or vocational activities.
      This is often done by a combination of electromyographical and kinesiological or
      biomechanical measurement techniques. Because there are over 400 skeletal muscles
      in the human body and both irregular and complex involvement of the muscles may
      occur in neuromuscular diseases and in voluntary occupational or sports
      movements, it is impossible to sample all of the muscles of the entire body
      during the performance of complex motor skills. In addition, the measurement of
      kinesiological EMG in sport and specific field circumstances, such as the track
      and/or soccer field, the alpine ski slope, the swimming pool and the ice rink,
      demands a specific technological and methodological approach, adaptable to both
      the field and the sport circumstances. Sport movement techniques and skills,
      training approaches and methods, ergonomic verification of the human-machine
      interaction have, amongst others, a highly specialized muscular activity in
      common. The knowledge of such muscular action in all its aspects, its evaluation
      and its feedback should allow for the optimization of movement, of sports
      materials, of training possibilities and, in the end, of sports performance.
      Drawing conclusions from a review of the EMG research of 32 sports, covering over
      100 different complex skills, including methodological approaches, is an
      impossible task. We have attempted to set standards concerning the EMG
      methodology at the beginning of this review. Electromyography and sports is a
      vast area and a complete review is impossible, as information will be found
      scattered in many different journals, including those on the sports sciences,
      ergonomics, biomechanics, applied physiology, in different congress proceedings,
      and so on. Consequently, many important aspects and possibly important
      publications may have been omitted from this review.

PMID- 8301705
TI  - Deformation characteristics of the heel region of the shod foot during a
      simulated heel strike: the effect of varying midsole hardness.
AB  - Impact tests using a pendulum were performed on the shod heel region of nine
      subjects. Both soft- and hard-soled shoes were used. The deformations involved
      were calculated from the registered decelerations during impact. Thus, load
      deformation cycles were recorded for various impact velocities. In contrast to in
      vivo force-platform recordings, peak loadings for the soft- and hard-soled
      conditions differed significantly (614 +/- 29 N vs 864 +/- 49 N, respectively),
      thus challenging the evidence for compensation at the level of the heel pad.
      Moreover, computation of the compression of the heel pad in the shoe showed an
      unexpected inverse relationship between shoe midsole hardness and degree of heel
      pad compression: the harder the midsole, the smaller the compression (soft shoe
      7.6 +/- 0.9 mm; hard shoe 6.7 +/- 0.9 mm). This can be explained by assuming a
      loading rate dependent stiffness of the heel pad in the shod condition (stiffness
      in N.m-1 = 51.25x (loading rate in N.s-1)0.76; R2 = 0.90), determined by the
      visco-elastic nature of the heel pad and the spatial confinement of the heel
      counter of the shoe.

PMID- 8301706
TI  - Effects of modelling and observer's ego involvement on warm-up decrement.
AB  - Warm-up decrement (WUD), a phenomenon associated with motor behaviour, is the
      temporary decrement that occurs when performance resumes after a period of
      inactivity. The purpose of this study was to examine the extent to which
      observing a model while concerned about one's own subsequent performance (e.g. a
      substitute about to enter the sport contest) influences WUD. The subjects were
      randomly assigned to one of four conditions: (1) observing an ego-involved model
      demonstrate the criterion skill, (2) observing a model while not ego-involved,
      (3) ego involvement without modelling and (4) resting (control). Performance
      outcome (accuracy) and arousal (cognitive and somatic) were assessed. The results
      of the study indicated that only the combined ego involvement plus modelling
      condition eliminated WUD. Positive rather than negative emotions and heart rate
      increased significantly for these subjects after rest. In contrast, the other
      conditions each exhibited WUD. Heart rate was significantly higher in the 'model
      and ego' and 'ego only' groups as opposed to 'modelling only' and rest.
      Implications for using cognitive strategies while observing competitors just
      prior to entering the contest on reducing WUD are discussed.

PMID- 8301707
TI  - Variability of hepatic vein Doppler tracings in normal subjects.
AB  - A prospective study was undertaken to determine the variability of hepatic vein
      Doppler waveforms in normal subjects. Seventy-five patients without liver or
      heart disease underwent Doppler examination of the middle hepatic vein. Normal
      triphasic tracings were observed in 68 subjects, while flattened tracings were
      observed in seven subjects. In addition, in four of the seven subjects with
      flattened tracings, an increase in pulsatility was seen during prolonged
      inspiration. We conclude that there is variability of hepatic vein tracings in
      normal subjects and that respiratory maneuvers can alter these tracings.

PMID- 8301708
TI  - Conventional and color Doppler transvaginal sonography of pelvic masses: a
      comparison of relative histologic specificities.
AB  - The relative specificity of CDS versus conventional TVS was assessed in 96 women
      with surgically excised and pathologically examined pelvic masses. In general,
      CDS was more specific than TVS in 43% of cases, both were equally specific in
      41%, neither was more specific in 10%, and TVS was more specific than CDS in 6%.
      In particular, CDS seemed to be most specific in detecting ovarian malignancies,
      ovarian torsion, and ectopic pregnancy. The positive and negative predictive
      values of CDS were higher in postmenopausal women than in premenopausal women.
      The use of CDS as an adjunct to TVS is supported by the data from this study.

PMID- 8301709
TI  - Diagnosis of subclavian steal in infants with coarctation of the aorta and
      interruption of the aortic arch by color-coded Doppler sonography.
AB  - We report the noninvasive diagnosis of subclavian steal by color-coded Doppler
      ultrasonography in nine infants with congenital heart disease. The underlying
      cardiovascular malformations included coarctation of the aorta in four infants,
      interrupted aortic arch type B in three patients, truncus arteriosus communis
      type A4 (one patient), and isolation of the right subclavian artery (one
      patient). In all patients both vertebral arteries could be displayed through the
      anterior fontanel in coronal sections. Normally the flow in both vertebral
      arteries, as well as the flow in the basilar artery, is displayed in red. In
      eight patients with angiographically proved unilateral subclavian steal, an
      antegrade (red) flow could be shown in one vertebral artery, whereas the
      contralateral vertebral artery was displayed blue, indicating reverse flow. In
      one infant with interrupted aortic arch type B and associated aberrant right
      subclavian artery, both vertebral arteries and the basilar artery were displayed
      blue, indicating bilateral subclavian steal. Color-coded Doppler sonography seems
      to be a sensitive, noninvasive method for diagnosing congenital subclavian steal,
      especially in infants with obstruction of the aortic arch.

PMID- 8301710
TI  - Reference ranges and ultrasonographic exposure conditions for pulsed Doppler
      sonographic studies of the fetal internal carotid artery.
AB  - We describe the 5th to 95th percentiles for the resistive index from the fetal
      internal carotid artery and measurements of (1) scanning time and (2) axial
      distance between transducer face and the fetal skull during pulsed Doppler
      examinations. Cerebral resistance peaks at 30 weeks' gestation and declines
      thereafter. The median duration of pulsed Doppler exposure was 31 seconds (range,
      4-80 seconds), and the median transducer-skull distance was 2.2 cm (range, 1.3
      6.2 cm). Our data provide reference ranges covering the entire period of fetal
      viability and help define ultrasonographic exposure conditions during pulsed
      Doppler examinations of fetal intracranial vessels.

PMID- 8301711
TI  - Ultrasonography of the sublingual space.
AB  - Fifty-three patients were evaluated by ultrasonographic visualization of the
      sublingual space as part of routine neck sonography. Delineation of the
      sublingual gland was good or fair in 93% of the cases. The normal gland was 32.06
      mm long in the sagittal plane. The submandibular duct was identified in 53% of
      the cases and measured less than 2.5 mm in diameter. The sublingual vessels were
      detected in 93% of the cases and had almost the same mean diameter as the duct.
      Four cases of frequent pathologies in this region were also examined.
      Ultrasonography is the examination to use for diseases of the sublingual space.

PMID- 8301712
TI  - A longitudinal study describing confidence limits of normal fetal cardiac,
      thoracic, and pulmonary dimensions from 20 to 40 weeks' gestation.
AB  - The current prospective, longitudinal study was designed to define the confidence
      limits and characteristics of growth for fetal cardiac, thoracic, and pulmonary
      dimensions from 20 to 40 weeks' gestation. We tested the hypotheses that (1)
      CC/TC, (2) CC/AC, (3) TC/HC, and (4) TC/AC ratios remain constant throughout this
      period of gestation. The four-chamber view of the fetal heart in diastole, in the
      absence of fetal breathing, was used as a standard reference for sonographic
      measurement of cardiac, thoracic, and left and right pulmonary dimensions in a
      longitudinal study of 45 uncomplicated pregnancies. Cardiac growth is best fit by
      a quadratic function: -8.147 + 0.900 (GA) - 0.0078 (GA)2. Similarly, thoracic
      growth is best fit by a quadratic function: -14.072 + 1.757 (GA) - 0.018 (GA)2.
      The characteristics of growth of the left and right lungs are best described by
      linear growth equations: -1.71 + 0.426 (GA) and -1.62 + 0.539 (GA), respectively.
      Each of the CC/TC, CC/AC, TC/HC, and TC/AC ratios changed significantly over
      time.

PMID- 8301713
TI  - Endometrial and myometrial thickness and uterine blood flow in postmenopausal
      women: the influence of hormonal replacement therapy and age.
AB  - The aim of our study was to assess the age and hormonal influence on endometrial
      and myometrial thickness and uterine blood flow in postmenopausal women. One
      hundred and nine healthy postmenopausal women were examined by transvaginal
      ultrasonography and color Doppler ultrasonography. Twenty women (18.4%) were
      under continuous HRT for at least 1 year. In all patients, full thickness of the
      endometrium and half thickness of the myometrium was measured. Pulsed Doppler
      waveforms were used to calculate the RI for the left and right uterine arteries.
      Endometrium thickness in the groups without HRT did not change as the years of
      postmenopause progressed. This was also true for myometrial thickness. The
      resistance to blood flow in the uterine arteries remained the same as the
      postmenopause progressed, but with each 5 year analysis, the ability to see the
      uterine arteries decreased. The duration of the therapy did not affect the
      measured parameters. The thickness of the endometrium was larger in the groups
      with HRT in comparison with all groups without HRT (P < 0.01). Myometrial
      thickness and uterine blood flow are not affected and did not show any
      significant influence from HRT. In conclusion, continuous HRT significantly
      influences the thickness of the postmenopausal endometrium but not of the
      myometrium or the uterine artery blood flow.

PMID- 8301714
TI  - Significance of peritoneal fluid identified by ultrasonographic examination in
      children with acute abdominal pain.
AB  - The purpose of this study is to evaluate the prevalence of free peritoneal fluid
      in children with abdominal pain, identify conditions associated with this
      finding, and determine the ability of ultrasonography to detect associated
      abnormalities. Two hundred and fifty children with acute abdominal pain and a
      reference group of 50 asymptomatic children were evaluated for the presence of
      free peritoneal fluid. Free peritoneal fluid was noted in 72 (29%) symptomatic
      and three (6%) asymptomatic children. A specific diagnosis was established in 39
      (54%) symptomatic children. The discharge diagnosis in the remaining 33 (46%)
      children was abdominal pain or gastroenteritis of unknown origin. Ultrasonography
      suggested the correct diagnosis in 29 out of 39 (74%) symptomatic children in
      whom a specific diagnosis was established at the time of discharge from the
      hospital. The presence of free peritoneal fluid detected by an ultrasonographic
      examination in children who have abdominal pain represents a nonspecific finding.
      Fluid is noted in association with a variety of abdominal and pelvic disorders.
      In approximately one half of symptomatic children with free peritoneal fluid, the
      final diagnosis is abdominal pain or gastroenteritis of unknown etiology. In the
      remainder, ultrasonography aids in the determination of a specific diagnosis.

PMID- 8301715
TI  - Auditory phenomena during transcranial Doppler insonation of the basilar artery.
AB  - During transcranial Doppler insonation of the basilar artery, 15 normal subjects
      heard high-frequency tones similar to tinnitus. The pitch of the tones equated
      with the PRF, and intensity equated with loudness. Alteration of pulse length did
      not change the tones heard, and the effect was highly dependent on probe position
      and direction. This is an example of ultrasonography acting as a sensory
      stimulus. The exact mechanism and implications of this effect will need to be
      clarified by further investigation. Although this phenomenon is not proved to be
      harmful, it would seem prudent to use the minimum transmitted power necessary to
      obtain a satisfactory signal from the basilar artery.

PMID- 8301716
TI  - Adjusted resistive index: a method to estimate rapidly renal blood flow:
      preliminary validation in hypertensives.
AB  - The Doppler RI, measured in a blinded fashion, was correlated with RBF, RVR, and
      GFR calculated by simultaneous clearance measurements. Nine hypertensive patients
      were studied weekly while receiving increasing doses of the vasodilator
      minoxidil. In 36 studies, RI was significantly correlated with RBF (r = -0.42)
      but not with RVR or GFR. When RI values were adjusted for ERV, correlations
      strikingly improved and were further improved by adjustment for pulse pressure.
      The ARI allowed semiquantitative predictions of RBF and RVR more accurately than
      blood urea nitrogen or serum creatinine levels. Correlation with GFR was weak.

PMID- 8301717
TI  - Spectrum of clinical presentation in fetal cystic renal disease: a case report.

PMID- 8301718
TI  - Prenatal diagnosis of congenital megalourethra.

PMID- 8301719
TI  - Infundibulopelvic stenosis: a sonographic diagnostic dilemma.

PMID- 8301720
TI  - Gartner's duct cyst with a single vaginal ectopic ureter and associated renal
      dysplasia or agenesis.
AB  - Two cases of Gartner's duct cyst with vaginal ectopic ureter and associated renal
      anomalies are reported. This unusual wolffian duct anomaly may be more common
      than previously suspected, especially in Asian patients. The radiologist and
      ultrasonographer should be aware of this anomaly and should perform a pelvic
      sonogram in any patient in whom there appears to be an absent or dysplastic
      kidney. Care should be taken to try and identify the Gartner's duct cyst
      extending caudally posterior to the base of the urinary bladder.

PMID- 8301721
TI  - An unusual neck mass in a fetus with Klippel-Trenaunay-Weber syndrome.

PMID- 8301722
TI  - Sonographic osseous manifestations of fetal syphilis: a case report.

PMID- 8301723
TI  - Aberrant subclavian artery: surgical treatment in thirty-three adult patients.
AB  - PURPOSE: Because of the scarcity of large series in the literature, our
      experience with surgery for aberrant subclavian arteries (aSA) in adults was
      reviewed. METHODS: During the last 16 years we have surgically treated 33 adult
      patients with aSA. Twenty-eight patients had a left-sided aortic arch with a
      right aSA whereas five had a right-sided aortic arch with a left aSA. Eleven
      patients (group 1) had dysphagia caused by esophageal compression by a
      nonaneurysmal aSA; five patients (group 2) had ischemic symptoms caused by
      occlusive disease of a nonaneurysmal aSA; 10 patients (group 3) had aneurysms of
      the aSA with or without symptoms caused by esophageal compression or arterial
      thromboembolism; and seven patients (group 4) had an aSA arising from a diseased
      (usually aneurysmal) thoracic aorta. In all cases the divided aSA was
      revascularized, most often by direct transposition into the ipsilateral common
      carotid artery. Nine of the 16 patients in groups 1 and 2 underwent operation
      with a cervical approach alone. In the remaining seven, the cervical approach was
      combined with a median sternotomy (six cases) or a left thoracotomy (one case).
      In the 17 patients in groups 3 and 4, either a cervical approach (two cases), a
      median sternotomy (four cases), or a two-staged approach combining a
      supraclavicular incision on the side of the aSA with a posterolateral thoracotomy
      on the side of the aortic arch (11 cases) was used. Aortic cross-clamping was
      required in 12 of these patients to perform the transaortic closure of the origin
      of the aSA with patch angioplasty (three cases), or prosthetic replacement of the
      descending thoracic aorta (nine cases). Cardiopulmonary bypass was used in six
      patients (including three with hypothermic circulatory arrest). RESULTS: Four
      patients, all in groups 3 and 4, died after operation: two of multiorgan failure,
      one of heart failure, and one of esophageal rupture. Satisfactory clinical and
      anatomic results were obtained in the remaining 29 patients. CONCLUSIONS: The
      surgical approach to aSA must be flexible and adapted to the anatomic conditions
      found. We recommend routine reconstruction of the aSA to avoid ischemic
      complications in the vertebrobasilar territory or upper extremity. Provision
      should be made for cardiopulmonary bypass in patients with aneurysm of aSA or
      associated aortic aneurysm.

PMID- 8301724
TI  - An assessment of the positive predictive value and cost-effectiveness of
      dipyridamole myocardial scintigraphy in patients undergoing vascular surgery.
AB  - PURPOSE: The approach to cardiac risk stratification of patients undergoing
      vascular surgery continues to be controversial. The success of algorithms that
      use clinical risk factors to determine cardiac risk have been inconsistent.
      Dipyridamole myocardial scintigraphy (DMS) has been accepted as a sensitive,
      noninvasive approach to risk stratification with excellent negative predictive
      value. Low positive predictive value (PPV) of abnormal DMS scans is a shortcoming
      that contributes to extensive preoperative cardiac evaluation and intervention
      with associated morbidity, mortality, and cost in most patients who undergo
      uncomplicated vascular procedures, regardless of DMS results. METHODS: Over 6
      years, 237 patients underwent DMS before surgical management of infrarenal aortic
      aneurysm, aortoiliac, or infrainguinal occlusive disease. The value of multiple
      clinical factors and DMS were assessed retrospectively for the prediction of
      perioperative myocardial infarction (MI), heart-related death, or preoperative
      selection for myocardial revascularization. Only congestive heart failure and two
      or more reversible defects on DMS were statistically significant on logistic
      regression analysis. RESULTS: The PPV of DMS was 19% for all patients with
      reversible defects, 12% for patients with one reversible defect, and 36.7% for
      patients with two or more reversible defects. The rates of cardiac death and MI
      were 1.3% and 5.9%, respectively. Perioperative echocardiography revealed
      unchanged postinfarction ejection fraction in most patients who experienced MI.
      Cost-effectiveness of DMS screening was evaluated. CONCLUSIONS: The costs per MI
      and cardiac death averted suggest a decline in cost-effectiveness of screening
      with DMS over time, assuming improving cardioprotective strategies of patient
      care. Clinical risk factors were minimally useful in the prediction of
      perioperative MI, heart-related death, or need for myocardial revascularization.
      The PPV of DMS is low, and the majority of MIs may be clinically insignificant.
      The cost-effectiveness of cardiac screening with DMS may not be justifiable given
      current trends of health care reform.

PMID- 8301725
TI  - Ischemic nephropathy and concomitant aortic disease: a ten-year experience.
AB  - PURPOSE: The durability of renal preservation after surgical intervention has not
      been well defined, particularly in patients with associated aortic disease. A
      review of all patients at the Emory University Hospital with renal insufficiency
      (creatinine level > or = 1.8) and concomitant atherosclerotic aortic and
      renovascular disease was undertaken. METHODS: Fifty patients underwent both renal
      revascularization (71 kidneys) and the repair of aneurysmal or symptomatic aortic
      occlusive disease between 1982 and 1992. Hypertension was present in 96% of
      patients and diabetes was present in 10%. The preoperative estimated glomerular
      filtration rate (EGFR) was 25.18 +/- 8.29 ml/min (creatinine level 3.1 +/- 1.5
      mg/dl). Operative management included bilateral renal artery repair (n = 21),
      unilateral repair alone (n = 17), and unilateral repair with contralateral
      nephrectomy (n = 12). The relative percent change in the postoperative EGFR (> or
      = 7 days after operation) increased by at least 20% in 42% of the patients, had
      decreased by 20% or more in only 4%, and was otherwise categorized as unchanged
      in the remaining 54% of the study group. RESULTS: The 30-day operative mortality
      rate was 2.0% (1 of 50). Forty-five of the surviving 49 patients (91.8%) were
      available for follow-up (median 49 months). During this period nine patients
      (18.4%) eventually required dialysis, four within 6 months of operation, and 19
      patients died. Neither subgroup experienced a retrieval of renal function after
      operation. Five-year survival rate was 61%, and a trend was noted between the
      risk of death and the relative change in EGFR after operation (p = 0.13). The
      likelihood of eventually requiring long-term dialysis was highest among those
      patients with low preoperative functional renal reserve as measured by
      preoperative creatinine level of 3 mg/dl or greater (p < 0.0001), or preoperative
      EGFR less than 20 ml/min (p = 0.0001). Blood pressure was cured or improved in
      50% at late follow-up. CONCLUSIONS: Early improvement of renal function may be
      observed in nearly one half of patients subjected to combined aortic and renal
      revascularization. Nonetheless, renal preservation may not be sustainable in
      patients with compromised preoperative function. Intervention before marked
      functional decline remains the best option for minimizing the risk of eventual
      dialysis.

PMID- 8301726
TI  - Performance of the vascular physical examination by residents and medical
      students.
AB  - PURPOSE: This study uses an objective structured clinical examination to evaluate
      the performance and interpretation of the vascular physical examination by
      interns and medical students. METHODS: A patient with lower extremity arterial
      occlusive disease findings was examined by 20 third-year students (M3), 23
      physicians entering surgical internship (PGY1), and 7 individuals completing
      internship (PGY2). The test consisted of two sections: part A evaluated the
      individuals' ability to perform a pulse examination (data gathering); part B
      evaluated the interpretation of the physical examination findings (data
      interpretation). National Board of Medical Examiners Part II examination results
      were obtained for 84% of participants. RESULTS: All groups performed poorly, with
      overall correct percent scores being 43% (M3), 39% (PGY1), and 62% (PGY2). PGY2s
      performed significantly better than M3s or PGY1s (p = 0.0002). No statistical
      difference was noted between M3 and PGY1 scores. Overall, data gathering skills
      were significantly better than data interpretation skills (51% vs 37%, p =
      0.0001). National Board of Medical Examiners Part II scores did not vary
      substantially among groups. CONCLUSIONS: Interns and medical students
      demonstrated considerable inaccuracy in both data gathering and data
      interpretation. A modest improvement was observed in individuals tested at the
      end of the internship year. This study suggests that increased attention should
      be directed toward instructing surgical residents and students how to perform an
      accurate peripheral vascular physical examination and how to interpret its
      significance.

PMID- 8301727
TI  - Saphenous vein patch versus primary closure for carotid endarterectomy: long-term
      assessment of a randomized prospective study.
AB  - PURPOSE: This study examines the long-term results of a randomized prospective
      study comparing primary versus saphenous vein patch (VP) closure after carotid
      endarterectomy (CEA). METHODS: One-hundred thirty-six patients undergoing 163
      CEAs over a 46-month period were prospectively randomized to VP, or primary
      closure. Patients with internal carotid artery diameters less than 5 mm and those
      requiring complex CEAs underwent obligatory vein patch (OVP). Patients were
      monitored with duplex scanning every 3 months for 1 year and every 6 months
      thereafter. All patients received aspirin. RESULTS: There were three
      perioperative strokes (one in the primary group, two in the OVP group) and no
      perioperative deaths. Two perioperative revisions were performed within 30 days
      of the original CEA for residual disease. During a mean follow-up of 59 +/- 4
      months, nine ipsilateral neurologic events have occurred, including two strokes
      and seven transient ischemic attacks. Sixteen patients had duplex evidence of
      recurrent stenosis, and one was associated with a stroke 36 months after CEA.
      Recurrence rates were similar in all groups (cumulative recurrence at 5 years:
      primary 7.8%, VP 14.3%, OVP 5.3%). Of the 136 patients (163 procedures), 72 (53%)
      (88 procedures) are alive and well, 16 (11.7%) (19 procedures) have been lost to
      follow-up, and 48 patients (35.3%) (56 procedures) have died. The cumulative
      stroke-free survival rate at 84 months was 71% for VP, 74% for OVP, and 60% for
      the primary group. CONCLUSIONS: These results demonstrate that CEA is a durable
      procedure. The use of VP closure did not produce superior long-term results
      compared with the use of primary closure in this select group of patients.

PMID- 8301728
TI  - Hemosuccus pancreaticus from intraductal rupture of a primary splenic artery
      aneurysm.
AB  - Hemosuccus pancreaticus--blood entering the gastrointestinal tract through the
      pancreatic duct--is a rare and elusive form of gastrointestinal bleeding. The
      most common cause is a splenic artery pseudoaneurysm caused by acute or chronic
      inflammation of the pancreas. We report the case of an 86-year-old woman who had
      recurrent gastrointestinal bleeding from erosion of an aneurysm of the splenic
      artery into the pancreatic duct. The lack of associated symptoms, equivocal
      endoscopic findings, and the rarity of this entity resulted in a delay in
      diagnosis. Nonresective treatment by ligation of the splenic artery proximal and
      distal to the aneurysm prevented any additional bleeding. Postoperative
      technetium sulfur colloid scanning demonstrated normal perfusion of the spleen.
      Only 16 cases of hemosuccus pancreaticus from primary splenic artery disease have
      previously been reported in the English-language literature (15 primary
      aneurysms, one medial disruption without an aneurysm). In contrast to cases
      caused by inflammatory pseudoaneurysms, splenic artery-pancreatic duct fistulas
      caused by primary aneurysms of the splenic artery should be treated without
      pancreatic or splenic resection, either with surgery or by embolization. In
      elderly patients with recurrent gastrointestinal bleeding of obscure source, the
      differential diagnosis should include the possibility of a ruptured aneurysm
      communicating with a viscus.

PMID- 8301729
TI  - Coxiella burnetii infection of pseudoaneurysm of an aortic bypass graft with
      contiguous vertebral osteomyelitis.
AB  - We report the case of a 67-year-old man who had an infection of a pseudoaneurysm
      of an aortic graft with contiguous vertebral osteomyelitis. The infectious
      organism was identified as Coxiella burnetii, a strict intracellular pathogen
      causing Q fever infection in humans. The patient was treated successfully with
      removal of the infected material in conjunction with extraanatomic bypass and
      specific antibiotic therapy. He is doing well after more than 3 years, with no
      evidence of recurrent periaortic infection on successive computed tomographic
      scans. We suspect that C. burnetii vascular graft infections could be
      underdiagnosed, because this cause is not frequently evoked. We suggest that
      extending the etiologic search to C. burnetii could decrease the number of
      undocumented vascular graft infections.

PMID- 8301730
TI  - Prosthetic replacement of the inferior vena cava after resection of a
      pheochromocytoma.
AB  - A 52-year-old man had an extensive right adrenal pheochromocytoma with invasion
      of the pararenal inferior vena cava (IVC). Tumor resection required en bloc
      resection of the infrahepatic IVC. The right kidney was not involved with tumor.
      Reconstruction of the IVC was performed with an externally supported, expanded
      polytetrafluoroethylene graft with reimplantation of the right renal veins into
      the prosthesis. Postoperative patency of the IVC graft and renal veins was
      confirmed by venacavography and color-flow duplex scanning. This latter technique
      has been used to document interval patency of the IVC graft 3, 6, and 12 months
      after surgery.

PMID- 8301731
TI  - An act of plagiarism.

PMID- 8301732
TI  - An act of plagiarism.

PMID- 8301733
TI  - An act of plagiarism.

PMID- 8301734
TI  - An act of plagiarism.

PMID- 8301735
TI  - Carotid endarterectomy when the distal internal carotid artery is small or poorly
      visualized.
AB  - PURPOSE: This is a report of the operative findings and results of carotid
      endarterectomy (CEA) when the conventional arteriogram demonstrates an internal
      carotid artery with a high-grade origin stenosis and a small or poorly visualized
      distal extracranial segment with an apparent diameter of 2 mm or less. METHODS:
      Eighteen CEA were performed on 17 patients with this preoperative finding and
      patent common and external carotid arteries. The indications for CEA were
      transient ischemia in seven patients, completed minor stroke in five and
      amaurosis fugax in four patients. One patient had bilateral findings and global
      cerebral ischemic symptoms. RESULTS: At CEA 16 internal carotid arteries had
      atherosclerotic very high-grade origin stenosis, and two had chronic occlusion.
      Ten of the 16 open arteries had true external diameters of 4 mm or more. Of
      these, seven were normal above the stenosis, two had a long, trailing
      intraluminal thrombus that was removed, and one had high-grade distal stenosis.
      Of the six arteries with true diameters of 3 mm or less (hypoplastic), two had a
      thick fibrotic wall. The carotid stump back pressure for the 16 open internal
      carotid arteries was 56 +/- 15 mm Hg (mean +/- SD). This was significantly higher
      than the 39 +/- 14 mm Hg back pressure measured in 1016 arteries without a string
      sign (p < 0.001). There was one 30-day postoperative death after a stroke. There
      was no systemic or neurologic morbidity. Post-CEA duplex scans demonstrated eight
      normal, five mildly stenotic, and five occluded internal carotid arteries. Two of
      the occlusions were found at CEA and the other three occluded arteries had low
      flow after CEA, two of which were hypoplastic and the other had a distal
      stenosis. CONCLUSIONS: Patients with symptoms with these findings on arteriograms
      should undergo CEA. However, the success of CEA in this setting depends on the
      internal carotid artery anatomy and disease, which is difficult to determine
      before CEA. Patients with a truly normal extracranial internal carotid artery
      have an excellent probability of a successful CEA, but this is not the case when
      the artery is small or fibrotic. Low internal carotid artery flow after a
      technically satisfactory CEA is a harbinger of thrombosis and should be managed
      by internal carotid artery ligation and external CEA.

PMID- 8301736
TI  - Carotid endarterectomy for unstable and compelling neurologic conditions: do
      results justify an aggressive approach?
AB  - PURPOSE: In a retrospective study the outcome of 70 carotid endarterectomies
      (CEA) in 68 patients with neurologically unstable conditions or anatomically
      compelling findings on carotid angiography was examined to more accurately
      identify patients who might benefit from CEA in this setting. METHODS: Out of a
      total of 1734 CEAs performed from 1978 to 1992, five groups of patients were
      selected: group A, stroke in evolution with tight stenosis (n = 5); group C,
      crescendo transient ischemic attacks (CTIA) continuing despite heparin (n = 14);
      group D, CTIA (above criteria) ceasing with heparin (n = 21); and group E,
      anatomically compelling situation on carotid angiography (n = 13). Data collected
      included preoperative and postoperative Neurologic Event Severity Score (NESS),
      CHAT classification, arteriosclerosis risk factors, demographics, and long-term
      overall and transient ischemic attack/stroke-free survival rates. RESULTS: Risk
      factors and demographics were similar in all groups. By NESS criteria the
      conditions of 97.3% of patients in the neurologically unstable groups A to C were
      improved or stabilized after operation, with one deterioration (2.7%). All
      patients in group B either stabilized or improved. In group D, one patient's NESS
      deteriorated, resulting in 3.5% overall morbidity rate and no deaths for groups A
      to D. Follow-up showed an overall survival rate by Kaplan-Meier analysis
      equivalent to a matched control population, with 85% alive at 5 years. The
      cumulative TIA/stroke-free survival rate at 5 years was 75%. CONCLUSIONS: In this
      retrospective series, CEA performed for compelling or unstable neurologic
      findings carried low morbidity and mortality rates. Early aggressive surgical
      therapy of neurologically unstable patients may be warranted because our results
      improved on the anticipated natural history of the conditions studied. Further
      clarification of proper patient selection is necessary before this principle can
      be applied broadly.

PMID- 8301737
TI  - Femorofemoral versus aortobifemoral bypass: outcome and hemodynamic results.
AB  - PURPOSE: Femorofemoral bypass (FFB) is used in selected patients when
      aortobifemoral bypass (AFB) is believed to be inappropriate because of high
      operative risk or predominantly unilateral iliac artery occlusive disease. We
      examined concurrent patients who underwent either FFB or AFB to better understand
      the appropriate use of FFB. METHODS: The characteristics and outcomes of patients
      who underwent FFB and AFB during 1986 to 1991 at our institution were
      retrospectively reviewed. Primary measures of outcome included patient survival,
      graft patency, limb salvage, and hemodynamic performance of FFB and AFB. Further
      analysis was performed after substratification for low versus high risk and
      claudication versus limb threat as the indication for surgery. RESULTS: FFB was
      performed in older patients with more medical comorbidities when compared with
      AFB. Long-term graft patency was inferior after FFB compared with AFB (60% vs 85%
      at 3 years, p < 0.01). However, both FFB and AFB achieved limb salvage in more
      than 85% of patients at 3 years. When patients at low risk undergoing
      nonemergency AFB were compared with patients at low risk who underwent FFB and
      who had no contraindication to AFB, FFB proved inferior to AFB as measured by
      graft patency (primary patency 61% vs 87% at 3 years, p < 0.03) and hemodynamic
      performance (predicted ankle-brachial index with perfect outflow 0.82 after FFB
      vs 1.03 after AFB). On the basis of a detailed analysis of patient and graft risk
      factors, we could not explain the inferior patency rate of FFB, although our
      analysis suggested that inadequate inflow may contribute. CONCLUSIONS: FFB is
      inferior to AFB as measured by patency and hemodynamic function. This inferior
      performance is independent of indications for FFB. AFB should remain the standard
      therapy for patients at low risk with iliac occlusive disease, but FFB provides
      adequate function and limb salvage in patients at high risk.

PMID- 8301738
TI  - A prospective, in vivo study of the relationship between blood flow hemodynamics
      and atherosclerosis in a hyperlipidemic swine model.
AB  - PURPOSE: This is the first prospective evaluation of the relationship between
      shear stress and atherosclerotic plaque formation in a pulsatile, in vivo model.
      METHODS: A 50% aortic stenosis was created in six Yucatan micropigs by placing a
      suture line across the left half of the aorta. A specially modified 20 MHz
      Doppler ultrasound probe mounted at a 45 degree angle on a micromanipulator was
      used to measure blood flow velocity along the lateral aspects of the aorta. Shear
      stress at these locations was calculated with linear regression. The pigs were
      then fed a specially formulated hyperlipidemic diet for 7 months, after which
      their aortas were harvested. Plaque thickness was measured and correlated with
      mean, maximum, and minimum shear stress at each site and side on or away from the
      aortic plication and distance from the level of the aortic plication with general
      linear modeling. RESULTS: Plaque thickness was negatively correlated with the
      mean shear stress during the cardiac cycle (correlation coefficient -0.3972 p =
      0.0164) and with the maximum shear stress during the cardiac cycle (correlation
      coefficient -0.4581 p = 0.0050). Plaque thickness was correlated with a
      multivariate model of mean shear stress, maximum shear stress, and their
      interactive effects with other parameters in the model with a correlation
      coefficient of 0.6733, (p = 0.0048). CONCLUSIONS: This is the first prospective,
      in vivo study with a pulsatile, hyperlipidemic model, which clearly demonstrates
      that low shear stress is associated with plaque formation.

PMID- 8301739
TI  - Farewell to surgery.

PMID- 8301740
TI  - Popliteal artery aneurysms: current management and outcome.
AB  - PURPOSE: Thrombosis of popliteal artery aneurysms can produce limb-threatening
      ischemia. In this setting we have found preoperative thrombolytic therapy to be
      beneficial. METHODS: Thirty-three patients with 54 popliteal artery aneurysms
      were studied (mean follow-up 62 months). Twenty-one patients (62%) had bilateral
      popliteal artery aneurysms, and 20 patients (61%) had extrapopliteal arterial
      aneurysms. Thirty-three (61%) aneurysms had symptoms of compression or ischemia,
      and 21 (39%) aneurysms had thrombosis. A trend toward thrombosis for larger
      aneurysms was noted (p < 0.068). RESULTS: Forty-five aneurysms were treated with
      bypass grafting. Five-year graft patency and limb salvage rates were 71% and 90%,
      respectively. Factors favoring graft patency and limb salvage included presence
      of two- or three-vessel runoff compared with patients with single- or no-vessel
      runoff (p < 0.025 graft patency; p < 0.003 limb salvage) and presence of a patent
      aneurysm (p < 0.005 graft patency and limb salvage). Seven patients diagnosed
      with thrombosis of their aneurysm and all runoff vessels were treated with
      preoperative thrombolytic therapy. Complete clearing of thrombus from these
      arteries was achieved in six of these patients (and from two of these runoff
      vessels in the remaining patient). These patients had better graft patency (p <
      0.005) and limb salvage (p < 0.01) than comparable patients treated with
      emergency operations. Six amputations were performed in the follow-up interval,
      none of which were performed in patients having undergone thrombolytic therapy.
      CONCLUSIONS: It is concluded that popliteal aneurysms are managed best by
      elective repair of patent aneurysms with good runoff. In that difficult situation
      of the thrombosed popliteal artery aneurysm associated with acute leg ischemia,
      thrombolytic therapy safely and effectively provides patients with a more
      favorable alternative than emergency surgery.

PMID- 8301741
TI  - The posterior approach to popliteal-crural bypass.
AB  - PURPOSE: An evaluation of the posterior approach to popliteal-crural bypass was
      performed to assess the feasibility and results of this technique. METHODS: A
      posterior approach to the popliteal and crural vessels was performed in 21
      patients in the prone position over a 24-month period, with use of lesser
      saphenous vein and a novel exposure of the crural arteries through the vein
      harvest incision. RESULTS: Diabetes mellitus was present in 17 (81%) patients,
      and all had limb-threatening ischemia with rest pain (15 patients, 71%),
      ulceration (7 patients, 33%), and gangrene (8 patients, 38%). The inflow site was
      the supragenicular popliteal artery in four patients (19%) and the infragenicular
      popliteal artery in 17 patients (81%). The outflow sites were the tibioperoneal
      trunk in six patients (29%), the peroneal artery in nine patients (43%), the
      posterior tibial artery in four patients (19%), and the anterior tibial artery in
      two patients (10%). The distal anastomosis was performed in the proximal one
      third of the crural artery in 16 (76%) of the patients, with a mean lesser
      saphenous vein graft length of 11.2 +/- 1.7 cm. The toe-brachial pressure indexes
      rose from 0.20 +/- 0.07 to 0.77 +/- 0.16 (p = 0.001), all wounds healed without
      complication, and 19 patients (90%) were discharged with open bypass grafts and
      salvaged extremities. The 6-, 12-, and 18-month primary graft patency rates were
      88%, 88%, and 83%, respectively (Kaplan-Meier methods). CONCLUSIONS: Thus the
      posterior approach to infragenicular occlusive disease represents a durable
      alternative to traditional approaches; sparing the greater saphenous vein,
      facilitating exposure of the proximal crural arteries, and minimizing the wound
      healing problems commonly experienced with standard techniques.

PMID- 8301742
TI  - Vascular complications from intraaortic balloons: risk analysis.
AB  - PURPOSE: The purpose of this study was to assess the incidence of and predictors
      for vascular complications in patients who required perioperative intraaortic
      balloon pump (IABP) support. METHODS: Data from 580 patients collected with a
      retrospective review were statistically analyzed with 25 perioperative
      parameters, and significant variables were evaluated with multivariate analysis.
      These data were also statistically compared with data from a 1983 study from our
      institution. RESULTS: Vascular complications occurred in 72 patients (12.4%). The
      three aortic perforations were fatal. Ipsilateral leg ischemia occurred in 69
      patients. Of these, ischemia was resolved in 82% of patients by IABP removal
      (21), thrombectomy (21), vascular repair (13), fasciotomy (2), or without
      intervention (2). Six patients died with the intraaortic balloon in place. Four
      patients required amputation for ischemia, but all survived. CONCLUSIONS:
      Vascular complications were not predictive of operative death (p = 0.26). Risk
      analyses with 25 perioperative parameters revealed that history of peripheral
      vascular disease, female sex, history of smoking, and postoperative insertion
      were independent predictors of vascular complications. However, most risk for
      vascular complications cannot be explained by these factors because of a low R2
      value. Compared with the results of our 1983 study, the incidence of IABP-related
      complications has not changed, but the severity of complications has decreased
      significantly, and IABP-induced death has decreased significantly.

PMID- 8301744
TI  - A piece of my mind. Family medicine to the fore.

PMID- 8301743
TI  - Penetrating atherosclerotic ulcers of the aorta.
AB  - PURPOSE: This study investigates the natural history and optimal imaging modality
      of penetrating atherosclerotic ulcers of the aorta. METHODS: We reviewed our
      experience with 29 penetrating ulcers in 18 patients. Computed tomography (17
      patients), magnetic resonance imaging (nine patients), and aortography (five
      patients) were used for diagnosis and follow-up. Patients were typically elderly
      (average age 74 years) and had hypertension and coronary artery disease. Ulcers
      were most common in the distal descending thoracic aorta (31%) and were
      characterized by a discrete ulcer crater (100%) and thickened aortic wall (89%).
      Modes of presentation included chest or back pain in four patients, distal
      embolization in two patients, and abnormal chest radiography results in one; the
      remaining were incidental findings. RESULTS: Follow-up was available in ten
      patients with 17 ulcers from 1 to 7 years. Recurrent pain occurred in two
      patients, recurrent embolization occurred in one patient, and seven patients
      remained symptom free. Progression to saccular pseudoaneurysm occurred in five
      ulcers, and fusiform aneurysm occurred in two ulcers. Two ulcers were associated
      with an increase in aortic diameter, and nine ulcers did not change. There were
      no cases of aortic dissection or rupture in the follow-up period. There were no
      deaths and only one patient underwent resection. CONCLUSION: The natural history
      of penetrating atherosclerotic ulcers is one of progressive aortic enlargement,
      with saccular and fusiform aneurysms the result if follow-up is sufficient.
      Aortic dissection, aortic rupture, and embolization can also occur but are less
      common. Contrast-enhanced computed tomography is the primary imaging modality.

PMID- 8301745
TI  - New guidelines encourage primary care for patients with early HIV infection.

PMID- 8301746
TI  - Use of antiretroviral drugs in HIV disease declines following preliminary results
      from Concorde trial.

PMID- 8301747
TI  - Massachusetts' new child abuse and neglect felony law repeals religious
      exemption.

PMID- 8301748
TI  - Military medicine takes late Gulf War hits; aeromedical evacuation improves as
      result.

PMID- 8301749
TI  - From the Agency for Health Care Policy and Research.

PMID- 8301750
TI  - From the Food and Drug Administration.

PMID- 8301751
TI  - From the Centers for Disease Control and Prevention. Deaths resulting from
      firearm- and motor-vehicle-related injuries--United States, 1968-1991.

PMID- 8301752
TI  - From the Centers for Disease Control and Prevention. Abortion surveillance:
      preliminary data--United States, 1991.

PMID- 8301753
TI  - From the Centers for Disease Control and Prevention. Hantavirus pulmonary
      syndrome, United States 1993.

PMID- 8301754
TI  - Increased cholecystectomy rate after introduction of laparoscopic
      cholecystectomy.

PMID- 8301755
TI  - Increased cholecystectomy rate after introduction of laparoscopic
      cholecystectomy.

PMID- 8301756
TI  - Does this patient have sinusitis?

PMID- 8301757
TI  - Does this patient have sinusitis?

PMID- 8301758
TI  - Does this patient have sinusitis?

PMID- 8301759
TI  - The right choice.

PMID- 8301760
TI  - The right choice.

PMID- 8301761
TI  - Do the poor sue more?

PMID- 8301762
TI  - Do the poor sue more?

PMID- 8301763
TI  - Gifts from industry: laundering money or supporting education?

PMID- 8301764
TI  - Molecular predictors of cognitive involvement in female carriers of fragile X
      syndrome.
AB  - OBJECTIVE: Fragile X syndrome is caused by a mutation involving expansion of a
      CGG trinucleotide repeat segment in the fragile X mental retardation-1 (FMR1)
      gene on the long arm of the X chromosome. This study was undertaken to determine
      the relative impact of three molecular characteristics of the FMR1 mutation-
      number of CGG repeats, methylation status, and X inactivation ratio--on the
      cognitive involvement of female carriers of fragile X syndrome. DESIGN:
      Retrospective study with new DNA analysis of known female carriers of fragile X
      syndrome. SETTING: Molecular studies were conducted in a university-based DNA
      diagnostic laboratory. Patients were originally ascertained through a regional
      fragile X clinic in a university-affiliated pediatric hospital. PATIENTS: Forty
      eight female carriers of fragile X syndrome were studied, including 22 with a
      premutation (a small expansion to approximately 50 to 200 CGG repeats), 23 with a
      full mutation (a full expansion to > 200 CGG repeats), and three with both types
      of mutations (mosaics). RESULTS: Median IQ score was significantly lower for
      females with a full mutation than for females with a premutation. No significant
      relationship was found between IQ score and number of CGG repeats or percentage
      methylation of the mutant allele within each mutation category. In addition, no
      significant relationship was found between IQ score and the proportion of normal
      FMR1 alleles on the active X chromosome in the carrier female group as a whole or
      in either mutation subgroup. Comparisons of leukocytes and saliva-borne
      epithelial cells in certain full-mutation carriers revealed striking differences
      in FMR1 mutation sizes. CONCLUSIONS: Mutation category remains the most important
      predictor of affectedness in female carriers of fragile X syndrome. Our data do
      not support use of the proportion of normal FMR1 alleles on the active X
      chromosome as a predictor of cognitive involvement in female carriers with full
      mutations. Individual tissue-specific differences exist in the heterogeneous
      sizes of full mutations and in the presence of premutation/full-mutation
      mosaicism.

PMID- 8301765
TI  - HIV infection and risk behaviors among heterosexuals in alcohol treatment
      programs.
AB  - OBJECTIVE: To measure the prevalence of human immunodeficiency virus (HIV)
      infection and high-risk behaviors among heterosexuals in alcohol treatment.
      DESIGN: Cross-sectional survey. SETTING: Five public alcohol treatment centers.
      SUBJECTS: Consecutive sample of 888 heterosexual clients entering treatment
      between October 1990 and December 1991. Respondents were 51% black, 10% Hispanic,
      33% white, and 76% male. The overall response rate was 68%. MEASUREMENTS:
      Structured interview and serotesting for HIV antibodies. RESULTS: The overall
      seroprevalence of HIV infection was 5% (95% confidence interval, 3% to 6%). There
      were no significant differences in rates of infection by age, gender, or race.
      The prevalence of infection in heterosexual respondents without a history of
      injection drug use was 3% in men and 4% in women, several times higher than
      published estimates from a similar community-based heterosexual sample. Unsafe
      sexual practices were common: 54% of respondents reported multiple sexual
      partners in the previous year, 97% of nonmonogamous respondents did not use
      condoms during all sexual encounters, and few respondents consistently asked new
      sexual partners about previous high-risk behaviors. CONCLUSIONS: There is a
      substantial prevalence of HIV infection among heterosexual clients in San
      Francisco (Calif) alcohol treatment programs, much of which is not associated
      with injection drug use. Because of this and the high prevalence of unsafe sexual
      behaviors, there is a relatively high likelihood of heterosexual spread of HIV
      among the large population of clients seeking treatment for alcohol dependency.
      Interventions to prevent HIV spread should become a standard part of alcohol
      treatment programs.

PMID- 8301766
TI  - A randomized trial of physical rehabilitation for very frail nursing home
      residents.
AB  - BACKGROUND: Past studies suggest multidisciplinary interventions that include
      physical therapy (PT) can improve function of nursing home residents. This trial
      specifically evaluates effects of PT for frail long-stay nursing home residents.
      DESIGN: Randomized, controlled trial. SETTING: One academic nursing home and
      eight community nursing homes. PATIENTS: A total of 194 elderly nursing home
      residents dependent in at least two activities of daily living residing in the
      nursing home for at least 3 months. INTERVENTIONS: Patients were randomized to
      individually tailored one-on-one PT sessions or friendly visits (FVs) three times
      a week for 4 months. Physical therapy included range-of-motion, strength,
      balance, transfer, and mobility exercises. MAIN OUTCOME MEASURES: Performance
      based physical function assessed by the Physical Disability Index; self-perceived
      health status assessed with the Sickness Impact Profile; observer-reported
      activities of daily living; and falls. RESULTS: Eighty-nine percent and 92% of PT
      and FV sessions, respectively, were attended; 5% and 9% of subjects dropped out
      in the PT group and FV group, respectively. Compared with the FV group, the PT
      group experienced no significant improvements in overall Physical Disability
      Index, Sickness Impact Profile, or activities of daily living scores. A 15.5%
      improvement in the mobility subscale of the Physical Disability Index was seen
      (95% confidence interval [CI], 6.4% to 24.7%); no benefits in range-of-motion,
      strength, or balance subscales were found. Compared with the FV group, the PT
      group used assistive devices for bed mobility tasks less often (P = .06) and were
      less likely to use assistive devices and wheelchairs for locomotion (P < .005).
      There were 79 falls in the PT group vs 60 falls in the FV group (P = .11). Charge
      for the 4-month PT program was $1220 per subject (95% CI, $412 to $1832).
      CONCLUSION: This standardized physical therapy program provided modest mobility
      benefits for very frail long-stay nursing home residents with physical disability
      due to multiple comorbid conditions.

PMID- 8301767
TI  - Immunization status of children of employees in a large corporation.
AB  - OBJECTIVE: To assess immunization levels for children of employees of a large
      corporation. DESIGN: A mail survey of a random sample of employees on the
      immunization history of one child per family. SETTING: US employees of Johnson &
      Johnson. PARTICIPANTS: 1500 employees with children born between 1984 and 1991.
      MAIN OUTCOME MEASURES: Coverage rates for recommended vaccines at different ages
      up to 6 years. MAIN RESULTS: Only 45.2% and 55.3% of the study children at ages 2
      and 6 years were current for all recommended immunizations (65.1% and 70.3%,
      respectively, excluding the Haemophilus influenzae type b vaccine). Using the
      minimum standard required by many states for school entry, the coverage level at
      age 6 years was 90.4%. Factors associated with higher immunization rates at age 2
      years were the corporate health plan (choices), higher pay level, greater
      parental formal education, white race, and knowing when to initiate immunization.
      Lower immunization rates at age 2 years were associated with delayed receipt of
      the first dose of diphtheria, tetanus, and pertussis vaccine, use of city or
      county clinics, employee-reported barriers of difficulty leaving work, and
      provider access problems, but not cost of services. After adjusting for the
      effects of other variables through logistic regression, race, pay level, and plan
      choice were no longer significant. Modeling with the remaining variables
      predicted rates of adequate immunization at age 2 years from 15% to 81%.
      CONCLUSION: Even in this relatively affluent group with good insurance (including
      immunizations), preschool immunization rates did not reach public health goals.
      Changing modifiable factors, such as knowing when to initiate immunization,
      enabling parents to leave work more easily, and improving provider access, might
      improve preschool immunization rates.

PMID- 8301768
TI  - Rochalimaea henselae infection. A new zoonosis with the domestic cat as
      reservoir.
AB  - OBJECTIVE: To determine the reservoir and vector(s) for Rochalimaea henselae, a
      causative agent of bacillary angiomatosis (BA) and cat scratch disease, and to
      estimate the percentage of domestic cats with R henselae bacteremia in the
      Greater San Francisco Bay Region of Northern California. DESIGN: Hospital-based
      survey of patients diagnosed with BA who also had significant exposure to at
      least one pet cat, as well as a convenience sampling of pet or impounded cats for
      prevalence of Rochalimaea bacteremia. SETTING: Community and university hospitals
      and clinics; veterinary clinics treating privately owned or impounded cats.
      PATIENTS: Patients with or without human immunodeficiency virus infection, with
      biopsy-confirmed BA, who had prolonged exposure to pet cats prior to developing
      BA. MAIN OUTCOME MEASURES: Cultures and laboratory studies were performed on
      blood drawn from pet cats associated with patients with BA. The Rochalimaea
      species infecting pet cats and fleas and causing the BA lesions in human contacts
      of these cats was identified by culture, polymerase chain reaction-restriction
      fragment length polymorphism analysis, and DNA sequencing. The presence of R
      henselae bacteremia in pet cats was documented, and predictor variables for
      culture positivity were evaluated. RESULTS: Four patients diagnosed with BA who
      had prolonged contact with seven pet cats were identified. The Rochalimaea
      species causing BA lesions in these patients was determined to be R henselae. The
      seven pet cats were found to be bacteremic with R henselae; this bacterium was
      also detected in fleas taken from an infected cat by both direct culture and
      polymerase chain reaction. Blood samples were cultured from pet and impounded
      cats (N = 61) in the Greater San Francisco Bay Region, and R henselae was
      isolated from 41% (25/61) of these cats. CONCLUSION: We have documented that the
      domestic cat serves as a major persistent reservoir for R henselae, with
      prolonged, asymptomatic bacteremia from which humans, especially the
      immunocompromised, may acquire potentially serious infections. Antibiotic
      treatment of infected cats and control of flea infestation are potential
      strategies for decreasing human exposure to R henselae.

PMID- 8301769
TI  - Advances in molecular analysis of fragile X syndrome.
AB  - Fragile X syndrome is a common cause of mental retardation that is inherited as
      an X-linked dominant disorder with reduced penetrance. Fragile X syndrome has
      been shown to be caused by an unstable CGG repeat within the fragile X mental
      retardation-1 (FMR1) gene. The repeat is normally polymorphic with six to 52
      repeats, while affected males and females exhibit a massive expansion resulting
      in 230 to more than 1000 repeats. Such expansions, called "full mutations," are
      associated with abnormal methylation of the FMR1 gene leading to transcriptional
      suppression. The resulting absence of the encoded protein, FMRP, a cytosolic RNA
      binding protein, is believed to result in the phenotype. Nonpenetrant male
      carriers and many female carriers exhibit premutation alleles of intermediate
      length (50 to 230 repeats), which are normally expressed. Male carriers transmit
      only unstable premutations while female premutation carriers can have carrier
      offspring with premutations or affected children with full mutations. The risk of
      having an affected child is directly related to the number of maternal repeats,
      with sequentially increasing probabilities of these alleles converting to full
      mutations as they are transmitted to subsequent generations. Advances have led to
      highly accurate laboratory diagnoses of both carrier and affected individuals as
      well as markedly improved prenatal diagnosis. In addition, a previously
      unrecognized class of mutation, later found responsible for several other
      important genetic diseases, has emerged.

PMID- 8301770
TI  - Familial hypercholesterolemia. What the zebra can teach us about the horse.

PMID- 8301771
TI  - Conflict of interest dilemmas in biomedical research.

PMID- 8301772
TI  - Fragile X syndrome. Improving understanding and diagnosis.

PMID- 8301773
TI  - Rochalimaea infections. Are they zoonoses?

PMID- 8301774
TI  - Antihypertensive therapy in a patient with gout and asthma.

PMID- 8301775
TI  - More magazines forgo tobacco ads, some by choice, many by chance.

PMID- 8301776
TI  - Smoking cigarettes may do developing fetus more harm than ingesting cocaine, some
      experts say.

PMID- 8301777
TI  - Legal challenge to medically correct smoking bans.

PMID- 8301778
TI  - Health experts to youth: don't give tobacco a start.

PMID- 8301779
TI  - Sports, medical officials call 'spit' tobacco 'out'.

PMID- 8301780
TI  - Tobacco use out of step with US Armed Forces.

PMID- 8301781
TI  - Smoke and letters.

PMID- 8301782
TI  - The hazards of involuntary smoking in the restaurant workplace.

PMID- 8301783
TI  - Nicotine don't get no respect.

PMID- 8301784
TI  - Nicotine dependence.

PMID- 8301785
TI  - Percutaneous mitral balloon valvotomy.

PMID- 8301786
TI  - Nicaragua: the role of USAID.

PMID- 8301787
TI  - Managed care, mental health, and the marketplace.

PMID- 8301788
TI  - Managed care, mental health, and the marketplace.

PMID- 8301789
TI  - Managed care, mental health, and the marketplace.

PMID- 8301790
TI  - Predicting smoking cessation. Who will quit with and without the nicotine patch.
AB  - OBJECTIVE: To identify predictors of smoking cessation success or failure with
      and without transdermal nicotine patch treatment. DESIGN: Two independent
      randomized, double-blind, placebo-controlled studies using the nicotine patch
      assessing outcome at the end of treatment and at 6-month follow-up; each study
      used a different mode of adjuvant counseling. PATIENTS: Subjects were daily
      smokers (> or = 15 cigarettes per day), aged 21 to 65 years with expired air
      carbon monoxide levels of at least 10 ppm, and motivated to quit. Eighty-eight
      subjects participated in study 1, and 112 subjects participated in study 2.
      INTERVENTION: Study 1 consisted of 8 weeks of 22-mg nicotine patch therapy with
      intensive group counseling. Study 2 consisted of 4 weeks of 22-mg nicotine patch
      therapy and 2 weeks of 11-mg nicotine patch therapy with brief individual
      counseling. MAIN OUTCOME MEASURES: The prediction of smoking cessation (at end of
      treatment and after 6 months) based on pretreatment and intratreatment measures
      in smokers using active or placebo nicotine patches. RESULTS: Pretreatment
      markers, such as the Fagerstrom Tolerance Questionnaire score, number of
      cigarettes smoked per day, years smoked, expired air carbon monoxide level, or
      baseline blood nicotine and cotinine levels, showed no consistent relationship
      with successful smoking cessation across both studies. Of the intratreatment
      markers examined, withdrawal severity and nicotine replacement levels also were
      not consistently predictive of cessation success. However, any smoking during the
      second week of treatment was a consistent and powerful predictor of failure at
      the end of treatment and after 6 months. Among active nicotine patch patients who
      smoked at all during week 2 after quitting, 83% and 97% (studies 1 and 2,
      respectively) were smoking at 6-month follow-up. Conversely, abstinence during
      the second week of treatment predicted successful smoking cessation. Among active
      nicotine patch patients who were totally abstinent during week 2 after quitting,
      46% and 41% (studies 1 and 2, respectively) were abstinent at 6-month follow-up.
      Of all nicotine patch patients in both studies who were smoking at 6-month follow
      up, 74% began smoking during week 1 or 2. Among all placebo patch patients who
      were smoking at 6-month follow-up, 86% began smoking during week 1 or 2.
      CONCLUSIONS: Smoking status (abstinent or smoking) during the first 2 weeks of
      nicotine patch therapy, particularly week 2, was highly correlated with clinical
      outcome and can serve as a powerful predictor of smoking cessation. Early smoking
      behavior also predicted outcome among placebo patch users. Traditional measures
      of dependence are not consistently predictive of cessation success. Clinicians
      are advised to emphasize the importance of total abstinence after a quit attempt
      and to follow-up with patients within the first 2 weeks of quitting; smoking
      during this critical time should be assessed and treatment may be altered as
      appropriate.

PMID- 8301791
TI  - Nicotine patch therapy for smoking cessation combined with physician advice and
      nurse follow-up. One-year outcome and percentage of nicotine replacement.
AB  - OBJECTIVE: To determine the efficacy of a 22-mg nicotine patch combined with the
      National Cancer Institute program for physician advice and nurse follow-up in
      providing withdrawal symptom relief, 1-year smoking cessation outcome, and
      percentage of nicotine replacement. DESIGN: Randomized, double-blind, placebo
      controlled trial. SUBJECTS: Two-hundred forty healthy volunteers who were smoking
      at least 20 cigarettes per day. INTERVENTIONS: Based on the National Cancer
      Institute program, subjects received smoking cessation advice from a physician.
      Follow-up and relapse prevention were provided by a study nurse during individual
      counseling sessions. Subjects were randomly assigned to 8 weeks of a 22-mg
      nicotine or placebo patch. MAIN OUTCOME MEASURES: Abstinence from smoking was
      verified by expired air carbon monoxide levels. Withdrawal symptoms were recorded
      during patch therapy, and the percentage of nicotine replacement was calculated
      by dividing serum nicotine and cotinine levels at week 8 of patch therapy by
      levels obtained while smoking. RESULTS: Higher smoking cessation rates were
      observed in the active nicotine patch group at 8 weeks (46.7% vs 20%) (P < .001)
      and at 1 year (27.5% vs 14.2%) (P = .011). Higher smoking cessation rates were
      also observed in subjects assigned to the active patch who had lower serum levels
      of nicotine and cotinine at baseline, and withdrawal symptom relief was better in
      the active patch group compared with placebo. CONCLUSIONS: Clinically significant
      smoking cessation can be achieved using nicotine patch therapy combined with
      physician intervention, nurse counseling, follow-up, and relapse prevention.
      Smokers with lower baseline nicotine and cotinine levels had better cessation
      rates, which provides indirect evidence that they had more adequate nicotine
      replacement with this fixed dose of transdermal nicotine than those smokers with
      higher baseline levels.

PMID- 8301792
TI  - Use of transdermal nicotine in a state-level prescription plan for the elderly. A
      first look at 'real-world' patch users.
AB  - OBJECTIVE: To assess transdermal nicotine use patterns and outcomes in a
      population of low-income older smokers. DESIGN: A 6-month telephone follow-up
      survey of smokers filling prescriptions for transdermal nicotine in the first 3
      months of 1992. SETTING: Pennsylvania's Pharmaceutical Assistance Plan for the
      Elderly, the nation's largest state-level prescription plan for the elderly.
      POPULATION: A total of 1070 noninstitutionalized male and female smokers aged 65
      through 74 years. MAIN OUTCOME MEASURES: Self-reported physician/pharmacist
      advice and adjunctive treatments, concomitant smoking, and 6-month smoking
      abstinence. RESULTS: Respondents were predominantly long-term heavy smokers. They
      used nicotine patches for an average of 5 weeks, with few reporting use beyond 3
      months or recalling bothersome side effects. Most of those with previous quit
      attempts rated quitting with the patch "easier." The 29% self-reported 6-month
      quit rate observed is encouraging. However, compliance with patch use guidelines
      was far from ideal in this high-risk population: only 54% of respondents received
      any initial advice or materials from their physicians or pharmacists, fewer than
      2% took part in a formal clinic or one-to-one treatment program, and almost half
      (47%) smoked while using the patch, including 20% who smoked every day.
      Concomitant smoking was strongly associated with failure to achieve abstinence (P
      < .001). More frequent contact with physicians and/or pharmacists was associated
      with less concomitant smoking (P < .001) and higher quit rates (P = .005).
      CONCLUSIONS: This survey offers an important first look at problems and prospects
      for nicotine patch therapy in older adults, with implications for other groups as
      well. Prospective studies are needed to clarify optimal treatment regimens and
      adjuncts.

PMID- 8301793
TI  - Smoking initiation by adolescent girls, 1944 through 1988. An association with
      targeted advertising.
AB  - OBJECTIVE: To identify trends in smoking initiation among persons aged 10 to 20
      years that might reflect the impact of specific targeting of tobacco advertising
      to women. DESIGN: Data from the National Health Interview Surveys on age of
      initiation of smoking (survey years 1970, 1978, 1979, 1980, 1987, and 1988) were
      used to construct age-specific rates of smoking initiation for males and females
      aged 10 to 20 years from 1944 through the middle 1980s. The raw rates were
      smoothed to allow trends to be more easily identified. PARTICIPANTS: Information
      from 102,626 respondents was used. RESULTS: In 18- to 20-year-old women,
      initiation rates peaked in the early 1960s and steadily declined thereafter. In
      girls younger than 18 years, smoking initiation increased abruptly around 1967,
      when tobacco advertising aimed at selling specific brands to women was
      introduced. This increase was particularly marked in those females who never
      attended college (1.7-fold higher). Initiation rates for females younger than 18
      years peaked around 1973, at about the same time sales of these brands peaked.
      After a steep postwar (1944 to 1949) decline, initiation rates in 18- to 20-year
      old men did not decrease until the middle to late 1960s. Initiation rates for
      boys younger than 16 years showed little change during the entire study period.
      CONCLUSIONS: The tobacco advertising campaigns targeting women, which were
      launched in 1967, were associated with a major increase in smoking uptake that
      was specific to females younger than the legal age for purchasing cigarettes.

PMID- 8301794
TI  - Sponsored symposia on environmental tobacco smoke.
AB  - OBJECTIVE--To test the hypothesis that symposia on environmental tobacco smoke
      (ETS) are more likely to present unbalanced data and be authored by tobacco
      industry-affiliated individuals than journal articles on ETS. To compare the
      publication records and affiliations of authors of symposia with the authors of
      scientific consensus documents on ETS. DESIGN--Content analysis of articles;
      computerized literature searches of English-language publications (except for one
      symposium) supplemented with additional sources. PARTICIPANTS (ARTICLES)--All 297
      symposium articles on ETS and a random sample of 100 journal articles on ETS
      published between January 1, 1965, and March 31, 1993; the 1986 Surgeon General's
      report on ETS; and the 1986 National Research Council's report on ETS. MAIN
      OUTCOME MEASURES--For each article, regardless of whether it had a methods
      section, agreement with the tobacco industry position that ETS is not harmful;
      topic; funding source(s); affiliation(s) of author; and publication records of
      authors. RESULTS--Of the symposium articles 41% were reviews, compared with 10%
      of journal articles. A total of 83% of original symposium articles and 100% of
      journal articles contained methods sections (P = .0001). Symposium articles were
      more likely to agree with the tobacco industry position (46% vs 20%), less likely
      to assess the health effects of ETS (22% vs 49%), less likely to disclose their
      source of funding (22% vs 60%), and more likely to be written by tobacco industry
      affiliated authors (35% vs 6%) than journal articles (P = .0001). Symposium
      authors published a lower proportion of peer-reviewed articles (71% vs 81%) (P =
      .0001) and were more likely to be affiliated with the tobacco industry (50% vs
      0%) than consensus document authors (P = .0004). CONCLUSIONS--Symposium articles
      on ETS differ from journal articles and consensus documents in ways that suggest
      that symposia are not balanced.

PMID- 8301795
TI  - The problem and sociocultural context of single-cigarette sales.
AB  - OBJECTIVE: To provide data on the sale of single cigarettes to adults and minors
      and to examine the sociocultural context in which these sales occur. DESIGN: A
      naturalistic observation study using repeated measures. Two hundred six stores in
      a convenience sample were visited by one minor and one adult who each attempted
      to purchase a single cigarette. MAIN OUTCOME MEASURES: Single-cigarette sales to
      an adult and/or minor. Data were obtained on type of store and, if a sale
      occurred, on the price, brand, and packaging of the cigarette. The ethnic
      composition of the neighborhood surrounding each store was determined. RESULTS:
      One hundred one (49.1%) of the stores sold single cigarettes. Singles were sold
      significantly more often to minors than to adults, and when both could make a
      purchase, minors paid more for these singles than did adults. Singles were least
      likely to be sold in white neighborhoods, more likely to be sold in integrated
      neighborhoods, and most likely to be sold in minority neighborhoods. Minors were
      able to purchase single cigarettes during 34.4% of the visits to white
      neighborhoods but could do so during 71.2% of the visits to minority
      neighborhoods; adults were able to make similar purchases during 24% of the
      visits to white neighborhoods and 37.3% of the visits to minority neighborhoods.
      CONCLUSIONS: The illegal sale of single cigarettes involves complex sociocultural
      factors heretofore unexamined. An understanding of such factors may be useful in
      planning merchant education programs and drafting policy to control illegal
      sales.

PMID- 8301796
TI  - Hair concentrations of nicotine and cotinine in women and their newborn infants.
AB  - BACKGROUND: To date, no biological markers have been identified that can predict
      the extent of fetal exposure to the toxic constituents of cigarette smoke. A
      variety of xenobiotic agents have been shown to accumulate in growing hair.
      PATIENTS AND METHODS: We measured maternal and neonatal hair concentrations of
      nicotine and cotinine in 94 mother-infant pairs. Mothers who were active smokers,
      nonsmokers, and passive smokers and their infants were included. RESULTS: Mothers
      who were active smokers (n = 36) had mean (SEM) hair concentrations of 19.2 (4.9)
      ng/mg for nicotine and 6.3 (4.0) ng/mg for cotinine, significantly higher than
      concentrations in nonsmokers (n = 35) (1.2 [0.4] ng/mg for nicotine and 0.3
      [0.06] ng/mg for cotinine, P < .0001). Infants of smokers had mean hair
      concentrations of 2.4 (0.9) ng/mg for nicotine (range, 0 to 27.3 ng/mg) and 2.8
      (0.8) ng/mg for cotinine (range, 0 to 12.2 ng/mg), significantly higher than
      concentrations in infants of nonsmokers (0.4 [0.09] ng/mg for nicotine and 0.26
      [0.04] ng/mg for cotinine, P < .01). Mothers with passive smoke exposure and
      their infants (n = 23) had significantly higher hair concentrations of nicotine
      (3.2 [0.8] ng/mg for mothers and 0.28 [0.05] ng/mg for infants) and cotinine (0.9
      [0.3] ng/mg for mothers and 0.6 [0.15] ng/mg for infants) than nonsmoking mothers
      and their infants (P < .01). There was a significant correlation between maternal
      and neonatal hair concentrations of nicotine (r = .49, P < .001) or cotinine (r =
      .85, P = .0001). CONCLUSIONS: This is the first biochemical evidence that infants
      of passive smokers are at risk of measurable exposure to cigarette smoke. Hair
      accumulation of cigarette smoke constituents reflects long-term systemic exposure
      to these toxins and therefore may be well correlated with perinatal risks.

PMID- 8301797
TI  - A missed opportunity. Teaching medical students to help their patients
      successfully quit smoking.

PMID- 8301798
TI  - The paradox of tobacco control.

PMID- 8301799
TI  - Smoking and young women. The physician's role in stopping an equal opportunity
      killer.

PMID- 8301800
TI  - Harry M. Vars Research Award. Influence of fasting on glutamine transport in rat
      liver.
AB  - During starvation, the liver switches from an organ of net glutamine uptake to an
      organ of net glutamine release to help maintain blood glutamine levels. We
      hypothesized that this shift in hepatic glutamine exchange was regulated at the
      level of the hepatocyte plasma membrane by adaptive changes in glutamine
      transport. To test this hypothesis, adult rats (200 g) were allowed to consume
      regular rat food ad libitum (fed, n = 8) or were fasted for 72 hours (fasted, n =
      8, access to water allowed). Livers were excised and hepatocyte plasma membrane
      vesicles were prepared by differential and Percoll density gradient
      centrifugation. Vesicle purity and functionality were assessed by marker enzyme
      measurements, classic "overshoots," and time courses, which showed similar
      vesicle size. Uptake of 3H-glutamine by hepatocyte plasma membrane vesicles in
      the presence and absence of sodium was assayed by a rapid mixing/filtration
      method, which reflects actual transport across the hepatocyte cell membrane in
      vivo. Fasted rats lost 15 +/- 2% of body weight; fed rats gained weight. Na(+)
      dependent glutamine transport (system "N," mediates uptake into the hepatocyte)
      fell by 22% in the starved group, indicating a diminished rate of glutamine
      transport into the hepatocyte. In contrast, carrier-mediated Na(+)-independent
      glutamine transport (system "n," mediates the release of glutamine out of the
      cell) doubled in the starved animals. Diffusion of glutamine across the vesicle
      membrane was unchanged by starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301801
TI  - Quality of life in long-term total parenteral nutrition patients and their family
      caregivers.
AB  - The purpose of this study was to identify individual and family variables
      associated with patient and caregiver quality of life. Perceived quality of life
      has been associated with improved outcomes and compliance. Methods included
      telephone interviews of 178 families, randomly selected from academic, hospital,
      and infusion agencies across the United States, with 116 follow-up questionnaires
      returned. Patients had varied bowel disorders requiring total parenteral
      nutrition for an average of 4.6 years. Patients were an average of 52.0 years
      old; caregivers averaged 52.5 years of age. Coded interview data indicated that
      caregivers assist patients daily (for a mean of 4.2 hours) and provide emotional
      support. Problems such as loss of friends, loss of employment, and depression
      were reported in two thirds of the families. Overall low quality of life was
      associated with length of time on total parenteral nutrition, fewer family coping
      skills, and inability to get along on income, whereas higher quality of life was
      associated with higher self-esteem and quality in the relationship. Preparing
      families for potential social problems or situations related to depression while
      also enhancing financial assistance, self-esteem, quality in the relationship,
      and coping skills may increase both patient and caregiver quality of life.

PMID- 8301803
TI  - Parenteral nutrition in cancer patients receiving chemotherapy: effects on
      toxicity and nutritional status.
AB  - The role of total parenteral nutrition (TPN) in reducing toxicity related to
      cancer chemotherapy (CT) is presently a controversial issue. To evaluate the
      effectiveness of TPN in reducing CT-associated toxicity and correcting and
      preventing CT-related impairments of nutritional status, a prospective crossover
      controlled study was performed in 43 cancer patients (19 normally nourished and
      24 malnourished) randomly divided into two groups (A and B). Group A patients
      received TPN concomitantly with the first course of chemotherapy, and the second
      course was administered 21 to 28 days later without TPN support; group B patients
      were treated in the opposite sequence. The rates of myelotoxicities and
      gastrointestinal toxicities after CT courses with or without TPN were essentially
      similar in normally nourished and malnourished patients. No changes in
      nutritional indexes were detected in normally nourished subjects after each
      course. Conversely, in undernourished subjects, prealbumin, retinol-binding
      protein, and nitrogen balance increased in CT+TPN courses (p < .02). In CT-only
      courses, undernourished subjects showed a decrease in prealbumin and nitrogen
      balance. Significant changes of nitrogen balance in CT vs CT+TPN courses were
      detected in malnourished subjects. TPN appears to be unable to reduce CT
      associated toxicity. CT administration does not result in any impairment of the
      nutritional status in normally nourished cancer patients. From our study, it
      appears that TPN should be limited to severely malnourished neoplastic patients
      undergoing CT, because of its ability to prevent further impairment of
      nutritional status and to improve the nitrogen balance and the levels of fast
      turnover visceral proteins.

PMID- 8301802
TI  - The role of the imino transporter protein in sepsis-impaired intestinal proline
      absorption.
AB  - Recently, sepsis has been shown to impair intestinal amino acid absorption in
      addition to gut metabolic and barrier functions. We investigated intestinal
      proline absorption in a rabbit model of sepsis. Twelve hours after
      intraperitoneal injection of lipopolysaccharide, proline uptake by everted
      jejunal sacs prepared from septic animals (480.4 +/- 67.4 nmol per sac per hour)
      was significantly reduced compared with controls (846.8 +/- 73.5 nmol per sac per
      hour) (p < .001 by t test). We next investigated whether reduced expression of
      transporter proteins contributed to the impaired intestinal proline uptake during
      sepsis. The proline (imino) carrier of rabbit jejunum is covalently bound by
      fluorescein isothiocyanate (FITC) and/or phenylisothiocyanate with irreversible
      inhibition of proline uptake. This binding and inhibition is prevented by sodium
      chloride and L-proline. Single-cell suspensions of rabbit enterocytes were
      prepared 12 hours after intraperitoneal injection of lipopolysaccharide/saline or
      saline alone. Enterocytes were incubated for 30 minutes in
      tris(hydroxymethyl)aminomethane/ethylenediaminetetraacetate (Tris/EDTA) buffer;
      buffer with 1 mM phenylisothiocyanate; or buffer with 10 mM proline, 100 mM
      sodium chloride, and 1 mM phenylisothiocyanate. After incubation with 10 microM
      FITC in Tris/EDTA buffer for 15 minutes, the percent positivity and fluorescent
      intensity of FITC binding to enterocytes were determined by using flow cytometry.
      Sepsis significantly reduced the percentage of enterocytes binding FITC and the
      fluorescent intensity of FITC binding of proline/sodium chloride-pretreated or
      untreated cells. This suggests that sepsis depresses the expression of imino
      transporters by rabbit enterocytes, which may explain the reduced intestinal
      proline absorption.

PMID- 8301804
TI  - Detrimental effects of an omega-3 fatty acid-enriched diet on wound healing.
AB  - The omega-3 fatty acids contained in fish oils have anti-inflammatory effects
      with potential beneficial clinical applications. However, these same effects may
      alter wound healing, a process dependent upon an adequate inflammatory response.
      The hypothesis that a diet enriched with omega-3 fatty acids could be detrimental
      to wound healing was tested in male rats fed complete diets differing only in
      their fat composition (17% menhaden oil + 3% corn oil vs 20% corn oil by weight)
      for 21 days before wounding and for 10 or 30 days after wounding (n = 16 per
      group). The wounding protocol included a dorsal 5-cm skin incision used for
      mechanical testing and a 2-cm incision used for subcutaneous polyvinyl alcohol
      sponge implantation. At 10 or 30 days postinjury, the 5-cm skin wounds were
      harvested and mechanically tested. The sponges were removed at 30 days and
      analyzed for collagen content. Food consumption and weight gain were the same in
      the two dietary groups. No differences in the mechanical properties of the wounds
      were detectable 10 days after injury. At 30 days, however, wounds harvested from
      rats fed the menhaden oil diet were significantly weaker than those from corn oil
      fed animals. This difference in tensile strength was not explained by
      differential collagen accumulation, inasmuch as the collagen content of the
      sponges at 30 days was the same in both groups. Dietary consumption of a diet
      rich in omega-3 fatty acids may conspire against the quality of wounds by
      altering the fibroplastic or maturational phases of the healing response.

PMID- 8301805
TI  - Odd-numbered medium-chain triglycerides (trinonanoin) in total parenteral
      nutrition: effects on parameters of fat metabolism in rabbits.
AB  - Odd-numbered medium-chain triglycerides (MCTs) might combine the advantages of
      "usual" MCTs applied in clinical nutrition with lower ketogenic action and the
      release of three carbon units. To test subacute toxicity, trinonanoin/long-chain
      triglyceride (LCT) (7/3 wt/wt) fat emulsions were given to rabbits (n = 8) for 11
      days (7 h/d) within a total parenteral nutrition regimen at a dose of 46.5% of
      total daily energy. Comparisons were made with rabbits receiving equicaloric
      amounts of MCT/LCT (7/3, wt/wt) or pure LCT fat emulsions, as well as with orally
      fed controls. The trinonanoin/LCT emulsion was well tolerated by all animals.
      Body weight changes showed no statistically significant differences between
      groups. The enzymatic determination of triglycerides, non-esterified fatty acids,
      and free glycerol concentrations in plasma samples revealed similar results for
      both MCT groups. However, ketone body concentrations (3-hydroxybutyrate) were
      significantly lower after trinonanoin/LCT emulsion administration. In the
      trinonanoin/LCT group, the plasma concentrations of propionic acid as well as of
      other short-chain fatty acids continuously increased; on days 10 and 11, elevated
      amounts of propionic acid were also detected in the urine. The histologic
      examination of the gut mucosa revealed no distinct differences between groups. On
      the basis of the presented data, the trinonanoin/LCT emulsion showed no
      inferiority to "usual" MCT/LCT emulsions. The lower ketogenic effect as well as
      the marked increase in plasma short-chain fatty acid concentrations may encourage
      further testing of this substrate for total parenteral nutrition.

PMID- 8301806
TI  - Urinary ammonia plus urinary urea nitrogen as an estimate of total urinary
      nitrogen in patients receiving parenteral nutrition support.
AB  - Nitrogen balance has historically been estimated by using urinary urea nitrogen
      (UUN) multiplied by a factor of 1.25 to account for nonurea nitrogen present in
      the urine. Recently, the reliability of UUN as an estimate of nitrogen losses has
      been questioned and the use of total urinary nitrogen (TUN) has been proposed as
      a more accurate measure of urinary nitrogen losses. However, analysis of TUN
      losses is not readily available in many hospital laboratories. Because ammonia is
      the major fluctuating component of urinary nonurea nitrogen and equipment to
      measure urinary ammonia is available in most hospitals, this study was undertaken
      to determine whether urinary ammonia plus UUN provides a clinically useful
      approximation of TUN. Twenty-four-hour urine samples acidified with boric acid
      during collection from 20 patients (a total of 42 samples) receiving total
      parenteral nutrition were analyzed for UUN, ammonia, and TUN. The UUN values
      ranged from 4.9 to 42.4 g/24 h. The mean difference between TUN and UUN was 1.99
      +/- 0.27 g/24 h. The mean difference between TUN and UUN plus ammonia was 0.78 +/
      0.27 g/24 h. Thus, UUN alone accounted for 90% and the combination of UUN plus
      urinary ammonia accounted for 96% of TUN. These data suggest that UUN plus
      ammonia does provide a greater level of reliability as an estimate of TUN than
      UUN alone.

PMID- 8301807
TI  - Supplemental arginine and ornithine do not affect splenocyte proliferation in
      surgically treated rats.
AB  - The present study was designed to determine whether arginine or ornithine
      supplementation enhanced immune responsiveness in surgically stressed rats. Young
      rats (130 to 150 g; n = 72) were fed one of three nonpurified diets: control,
      arginine-supplemented (30 g/kg of diet), or supplemented with ornithine on an
      equimolar basis to supplemental arginine. Control and ornithine-supplemented
      diets were made isonitrogenous to the arginine-supplemented diet with alanine.
      Food intake and body weight were monitored throughout the experimental period.
      Eight days after initiation of dietary treatments, 36 rats were given dorsal skin
      wounds. Rats were killed 7 days later. Blood was collected, spleen and thymus
      were weighed, and splenocytes were isolated to measure proliferation in response
      to mitogens and interleukin-2 production. Food intake, body weight gain, and
      thymus weight were lower in rats subjected to surgery than in controls rats (p <
      .01). Neither supplemental dietary arginine nor ornithine affected food intake,
      body weight gain, thymus weight, splenocyte proliferation, or splenocyte
      interleukin-2 production in any treatment group (p < .1). These data suggest that
      low-level dietary supplementation of arginine and ornithine did not ameliorate
      detrimental effects of minor surgery in rats.

PMID- 8301808
TI  - Meconium passage in very-low-birth-weight infants.
AB  - The timing of the first meconium stool has been considered a marker for proper
      gastrointestinal functioning in the term infant. There is limited information on
      the meconium passage patterns of very-low-birth-weight infants of less than 32
      weeks' gestation. It is unknown whether feeding practices influence the timing of
      the first stool in these infants. We retrospectively studied 47 very-low-birth
      weight infants with birth weights of 1250 g or less who were previously enrolled
      in a study of gastrointestinal (GI) priming. Infants whose mothers desired to
      breast feed (n = 7) were given GI priming with their own mother's milk. The
      remaining infants had been randomly assigned to receive total parenteral
      nutrition alone (n = 21) or GI priming with infant formula (n = 19) during the
      first 14 days of life. We attempted to advance all infants to full enteral
      nutrition by 21 days of age. There was no statistically significant difference in
      timing of the first stool among the three groups. The overall median age at first
      stool was 43 hours, and the 75th percentile was 10 days. The range was 1/2 hour
      to 27 days. There was no concordance between time of first stool and birth weight
      within the range studied. There was no concordance between time of first stool
      and necrotizing enterocolitis, although there was little statistical power to
      detect this. There was also very little concordance with feeding tolerance. Other
      than necrotizing enterocolitis, no significant GI disease developed in any of the
      infants studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301809
TI  - Nutritional parameters observed during 28-day infusion of recombinant human tumor
      necrosis factor-alpha.
AB  - In conjunction with a Phase I investigation of the antineoplastic activity of
      recombinant human tumor necrosis factor-alpha (TNF-alpha), administered as a 28
      day continuous infusion, selected nutritional parameters were evaluated to
      identify any effect that might be attributed to the TNF infusion. Seven
      clinically stable men with a variety of tumor types were studied. None had
      clinical or laboratory evidence of significant malnutrition before entry into the
      study. Five patients received 10 micrograms of recombinant human TNF-alpha per
      square meter per day and two patients received 25 micrograms/m2 per day. Indirect
      calorimetry assessment of resting energy expenditure, body weight, serum TNF
      concentration, and laboratory analysis of common nutritional markers (albumin,
      prealbumin, and triglycerides) were performed at baseline, day 14, day 28, and 2
      weeks (day 42) after completion of the infusion. There were no statistically
      significant differences by analysis of variance observed in any parameter during
      the study period compared with baseline values and values on day 42. Also, there
      were no differences between any parameters when stratified by dose administered,
      although the number of patients studied was small. Measured serum TNF
      concentrations ranged from 0.02 to 1.56 ng/mL and did not correlate with study
      day or dose of TNF infused. No correlation was observed between serum TNF
      concentrations and resting energy expenditure. Although others have reported
      significant metabolic changes associated with acute administration of TNF in
      humans and animals, our experience does not support a hypermetabolic state in
      patients receiving low daily dose, long-term (28-day) continuous infusion of
      recombinant human TNF-alpha, a state that may be consistent with many neoplastic
      conditions.

PMID- 8301810
TI  - Limitations of percutaneous endoscopic jejunostomy.
AB  - Thirty-six patients at the University of Kentucky Medical Center underwent
      percutaneous endoscopic jejunostomy placement between January 1 and December 31,
      1989. We retrospectively reviewed their charts for indications and complications
      of the procedure. Experience and outcome with the initial placement of the
      percutaneous jejunostomy tube was evaluated. Primary diagnoses at the time of
      insertion included central nervous system disorders (28), ventilator dependence
      (5), cancer (2), and gastroparesis (1). The follow-up period ranged from 2 to 131
      days (median 16 days). Tube dysfunction or dislodgment occurred in 31% of
      patients. Other complications included pulmonary aspiration (11%) and bleeding at
      the insertion site (3%). The 30-day mortality rate was 19% with all but one death
      caused by the severity of the underlying primary illness. It is concluded that
      problems with the currently performed technique of percutaneous endoscopic
      jejunostomy, along with tube-related problems, seriously limit the usefulness of
      this technique. Improvements in technology, along with routine postprocedure
      radiographs to allow early detection of malpositioned jejunostomy tubes, may
      improve the outcome of this procedure. Newer techniques that have a higher
      success of distal small intestinal placement need to be evaluated.

PMID- 8301811
TI  - Amino acid loss and plasma concentration during continuous hemodiafiltration.
AB  - Amino acid loss, plasma concentration, and the relationship between amino acid
      intake and balance during continuous hemodiafiltration (CHD) were investigated in
      a prospective, nonrandomized study of trauma patients exhibiting the systemic
      inflammatory response with acute renal failure. Data were compared with those
      from a group of similar patients who had maintained renal function (control).
      Both groups received similar amounts of nonprotein calories (3015 +/- 753
      nonprotein calories per day in the control group vs 3077 +/- 1018 nonprotein
      calories per day in the CHD group) and amino acids (2.24 +/- 0.36 g/kg per day in
      the control group vs 2.19 +/- 0.48 g/kg per day in the CHD group) via the
      parenteral route. Amino acid solutions were either 19% or 45% branched-chain
      amino acid enriched. Studies were performed every 12 hours for a maximum of 6
      days. Amino acid loss was 2.5 +/- 2.3 g/12 h in the control group vs 6.6 +/- 2.4
      g/12 h in the CHD group (p < .0001). Increasing the dialysate rate from 15 to 30
      mL/min increased amino acid loss from 5.7 +/- 1.7 to 7.9 +/- 2.6 g/12 h (p <
      .0001). Amino acid loss was unrelated to amino acid intake but was directly
      related to plasma amino acid concentration, CHD effluent volume, and the
      efficiency of filtration as measured by the ratio of filtered urea nitrogen to
      blood urea nitrogen (R2 = .69). A linear relationship was found between amino
      acid intake and balance (R2 = .991). The patterns of plasma amino acid
      concentrations were consistent with metabolic changes wrought by a combination of
      sepsis and multiple organ dysfunction and type of amino acid intake but seemed
      unaffected by increased amino acid loss in CHD effluent. Amino acid losses were 2
      to 3 times greater from CHD than from normal kidney. However, CHD amino acid
      losses may not be clinically significant unless amino acid intake is restricted
      to levels used typically in traditional hemodialysis.

PMID- 8301812
TI  - Nasointestinal tube placement with a pH sensor feeding tube.
AB  - Radiographic confirmation of enteral feeding tube placement is a common practice
      representing considerable expense and causing delay in the initiation of enteral
      nutrition therapy. We evaluated an enteral feeding tube with a pH sensor, which
      allows immediate verification of the location of the tube by assessment of the pH
      upon insertion. Insertion pHs were obtained for 24 intensive care unit patients
      requiring feeding tube placement. Placement was verified radiographically and
      compared with expected location on the basis of the pH profile. The radiograph
      and the insertion pH profile were in agreement in 87.5% (21 of 24) of the cases.
      Concomitant use of histamine blockers did not affect the ability of the pH sensor
      to detect placement accurately (Fisher's Exact Test, p 5.71) Use of these pH
      measurements eliminates the need for radiographic documentation of placement,
      provides a savings for the patient, and may be beneficial in promoting enteral
      feedings in critically ill patients.

PMID- 8301813
TI  - Staphylococcus saprophyticus sepsis related to total parenteral nutrition
      admixtures contamination.
AB  - The aim of this study was to report an outbreak of sepsis related to
      contamination of total parenteral nutrition (TPN) admixtures with Staphylococcus
      saprophyticus. A total of four patients developed fever after administration of
      contaminated TPN. Results of cultures of blood, catheter hubs and tips, and TPN
      admixtures are presented. The strain responsible for the outbreak was able to
      grow in vitro in two common TPN formulations.

PMID- 8301815
TI  - Exit site purse-string suture to secure long-term venous catheters.
AB  - A new method for the prevention of accidental dislodgment of long-term venous
      catheters involves the use of an exit site purse-string suture that holds the
      catheter cuff in place before the ingrowth of fibrous tissue. This method is
      safe, reliable, easily reproduced, and does not require any additional incisions
      or anchoring devices. In our clinical practice, it has drastically reduced the
      number of accidental dislodgments.

PMID- 8301814
TI  - Pulmonary embolism as a complication of long-term total parenteral nutrition.
AB  - Although much has been written concerning the complications of long-term total
      parenteral nutrition, little or no mention of pulmonary embolism is made in the
      literature. We present two patients maintained on home total parenteral nutrition
      who suffered pulmonary emboli, one while receiving standard heparin therapy. No
      potential source other than their indwelling total parenteral nutrition catheter
      was identified. Studies have revealed catheter-related thrombosis in up to 50% of
      patients with indwelling central venous catheters. Although early surgical
      literature suggested that upper extremity deep vein thromboses rarely embolize,
      more recent investigations have proven this false. In fact, the risk of pulmonary
      emboli appeared to be greatest in those thrombi that were catheter related.
      Because of this risk, we suggest a hypercoaguable work-up in any patient with a
      history of recurrent thrombosis. Heparin is central to the current preventive
      regimens; however, further study is needed to determine the most efficacious
      dose. Future development of less thrombogenic catheters will also be of
      assistance. Thrombolytic agents currently have an expanding role in the treatment
      of thrombotic complications. Whether they will have a future role in prevention
      remains unknown.

PMID- 8301816
TI  - Prevalence of malnutrition in alcoholic and nonalcoholic medical inpatients: a
      comparative anthropometric study.

PMID- 8301817
TI  - Peripheral and parenteral nutrition: preliminary report on its efficacy and
      safety.

PMID- 8301818
TI  - [Clinical study on total intravenous anesthesia with droperidol, fentanyl and
      ketamine--20. Summary of three thousand cases and the future of this anesthetic
      method].
AB  - Total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK) was
      given to over three thousand patients during four years from April 1989 through
      March 1993. The patients ranged in age from three months to eighty seven years.
      They underwent surgical, orthopedic, gynecological, thoracic, plastic and
      otolaryngeal surgeries, but patients who underwent craniotomy and obstetric
      operations were excluded. None of them developed any serious complications
      primarily due to DFK. DFK has many advantages such as the broad safety margin for
      three agents employed in DFK, no accident by N2O, no air pollution, empty bowels,
      no increase in middle ear pressure etc, while this has disadvantages such as high
      blood pressure, slow awakening from anesthesia and unpleasant dreams. Calcium
      channel blockers are very effective for antagonizing high blood pressure, and
      rapid recovery from anesthesia can be easily obtained by reducing ketamine dose
      given and also by application of epidural block. Intraoperative dreams may be
      avoided by concomitant use of benzodiazepines. Thus we are convinced that DFK can
      be a good as well as convenient anesthetic method for clinical anesthesia.

PMID- 8301819
TI  - [Rapid induction of anesthesia with inhalation of sevoflurane].
AB  - Induction of anesthesia with inhalation of sevoflurane was evaluated in 45
      patients. Inhalation anesthesia was induced by a single vital capacity breath
      followed by spontaneous breathing. The compositions of anesthetic gases were as
      follows: 5% sevoflurane in oxygen, 5% sevoflurane in 67% nitrous oxide and
      oxygen, and 7% sevoflurane in 67% nitrous oxide and oxygen. The time (mean +/-
      SEM) necessary for the loss of consciousness was 85 +/- 6, 56 +/- 4, and 42 +/- 3
      seconds, and breathing frequency was 8 +/- 1, 5 +/- 0.6, 1.4 +/- 0.2, in each
      composition of anesthetic gasses, respectively. Changes in blood pressure and
      heart rate were relatively small. The technique was found to be acceptable to all
      of the patients studied. We conclude that the technique of single breath
      induction with sevoflurane is a safe and acceptable alternative to intravenous
      induction in cooperative adult patients.

PMID- 8301820
TI  - [Effects of sevoflurane on hemodynamics during the induction of anesthesia
      compared with those of isoflurane, enflurane and halothane].
AB  - The effects of sevoflurane (S), isoflurane (I), enflurane (E) and halothane (H)
      on hemodynamics were studied in 50 patients during the inhalation of 1.5 MAC of
      each anesthetic before the surgery. Mean arterial pressure (MAP), heart rate
      (HR), cardiac index (CI), systemic vascular resistance index (SVRI) and stroke
      volume index (SVI) were measured noninvasively using the automatic blood pressure
      manometer and the ultrasonic Doppler method (Accucom). There were significant
      differences between E and H in MAP, CI, SVRI and SVI. The values of CI, SVRI, SVI
      with S, as well as with I, were between those of E and H. These results indicate
      that sevoflurane causes the depression of blood pressure mostly by decreasing
      afterload during the induction of anesthesia, although the decrement with
      sevoflurane, as well as that with isoflurane, is less than that with enflurane.

PMID- 8301821
TI  - [Effects of different concentrations of an inhaled anesthetic agent, sevoflurane
      on sympatho-adrenal medullary functions in rats].
AB  - Effects of different inspiratory concentrations of an inhaled anesthetic agent,
      sevoflurane on efferent activities of the adrenal sympathetic nerve and adrenal
      catecholamine secretion were examined using rats either under the resting
      condition or during noxious mechanical stimulation of a hindpaw. Under the
      resting condition, an increase in the inspiratory concentration of sevoflurane
      from 2.1% to 4.2% caused a gradual decrease in the adrenal nerve activity and the
      catecholamine secretion. When noxious mechanical stimulation was applied to a
      hindpaw by pinching, both the adrenal nerve activity and adrenaline secretion
      increased, and the responses were attenuated dose-dependently by sevoflurane
      concentration of between 2.1% and 4.2%. Noradrenaline secretion was unchanged
      during the pinching stimulation throughout the administration of sevoflurane 2.1
      4. 2%.

PMID- 8301822
TI  - [Comparison of buprenorphine and fentanyl for postoperative pain relief by
      continuous epidural infusion].
AB  - This study examined analgesic efficacy and adverse effects of buprenorphine and
      fentanyl for the postoperative pain relief by continuous epidural infusion. Fifty
      patients after upper or lower abdominal surgeries were assigned to two groups and
      buprenorphine and fentanyl were epidurally administered postoperatively.
      Buprenorphine (B) group received bolus injection of B 0.1mg + saline 8 ml and
      continuous infusion of B 0.8 mg+saline 92 ml (2 ml.h-1). Fentanyl group received
      bolus injection of F 0.1 mg+saline 6 ml and continuous infusion of F 0.6
      mg+saline 84 ml (2 ml.h-1). There was no significant difference between the two
      groups in the analgesic efficacy, which became lower from 2 to 12 hours
      postoperatively. However, compared with buprenorphine group, the incidence of
      nausea or vomiting and dizziness was significantly less in the fentanyl group (11
      vs. 4 cases and 7 vs. 1 cases). These results imply that the major site of action
      of epidurally administered fentanyl is the spinal cord. In contrast, analgesic
      effect of epidural buprenorphine appears to be enhanced by the supraspinal
      action. We conclude that fentanyl is superior to buprenorphine for postoperative
      pain relief by continuous epidural infusion.

PMID- 8301823
TI  - [Postoperative pain therapy: a survey of patient attitudes to postoperative pain
      relief].
AB  - We surveyed the attitudes of general surgical patients to the management of their
      postoperative pain relief. Elective surgical patients (n = 232) were asked
      postoperatively about their experienced pain which was expressed according to
      verbal pain scale, the duration of experienced pain, satisfaction with pain
      relief and medication, and expectations of pain on the 5th to 7th postoperative
      day. Thirteen percent of the patients had no pain, 47% of whom had no rest pain
      but pain on moving or coughing, 32% of whom had rest and moving pain, and 0.4% of
      whom experienced horrible and excruciating pain. Duration of postoperative pain
      was 2.5 +/- 1.9 days, and 76% of the patients experienced pain only for 3
      postoperative days. Results of the interviews indicated that 80% of these
      patients were satisfied with their postoperative pain relief. Although 80%
      expressed satisfaction, 39% of whom did have rest pain. In the patients with
      continuous epidural infusion of buprenorphine and 0.25% bupivacaine, incidence of
      complained rest pain was significantly low compared with those with intermittent
      i.v. and/or im injection of analgesics on demands of patients. Lag between
      patient's demand and nurse's response concerning medication correlated
      significantly to the satisfaction. There was no relation between satisfaction and
      age, the nature of operation or sex. Fifty-two percent of the patients reported
      that degree of experienced pain had been less than expected preoperatively. In
      conclusion, 80% of the patients were satisfied, but our postoperative pain
      therapy was still insufficient because 39% of them had rest pain.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301824
TI  - [The effects of hyperventilation upon the spinal pain modulating system].
AB  - The purpose of this study is to investigate the effects of hyperventilation on
      the wide dynamic range (WDR) cell of the dorsal horn of the feline lumbar spinal
      cord. Cats received midcollicular decerebration and lumbar laminectomy. The
      spinal cord was transected at T12-L1. WDR cells were sampled with microelectrode
      at the depth of 2,000 microns from the cord dorsum. Following the control period
      with PaCO2 of 35-45 mmHg, respiratory rate and tidal volume were adjusted to make
      a level of hypocapnia as low as 20-25 mmHg. The recovery of cell activity was
      followed when normocapnia was restored. Hypocapnia with PaCO2 of 25-30 mmHg and
      20-25 mmHg suppressed the activity of WDR cell significantly. At PaCO2 of 25-30
      mmHg, the spontaneous activity was suppressed for about 20% and evoked activity
      for 27%. At PaCO2 of 20-25 mmHg, the spontaneous activity was suppressed for
      about 50% and evoked activity for 33%. The results suggest that the
      hyperventilation has suppressive effects on single-unit activity of WDR cell.

PMID- 8301825
TI  - [The effect of PaO2 on apneic threshold PCO2 (PATCO2)].
AB  - Recovery from posthyperventilation apnea accompanies a rise in PaCO2, and
      ventilation starts only when the PaCO2 attains the apneic threshold PCO2
      (PATCO2). In the present study, we evaluated the effect of decreasing PaO2 on
      PATCO2 under light enflurane anesthesia in 17 female patients undergoing elective
      surgery. The apnea was produced by hyperventilating the lungs under two different
      conditions [with 1.3% (end-tidal) enflurane in 100% O2 or with 1.3% enflurane in
      30% O2]. The initiation of ventilation after apnea was identified by the first
      expiratory act observed in capnogram, at which time an arterial blood sample was
      taken to determine PATCO2. The values of PaO2 at the initiation of ventilation
      with 1.3% enflurane in 100% O2 and 1.3% enflurane in 30% O2 were 394.7 +/- 65.0
      mmHg (mean +/- SD), and 51.9 +/- 18.2 mmHg, respectively. There was a significant
      difference between the two values (P < 0.001). The values of PATCO2 with 1.3%
      enflurane in 100% O2 and 1.3% enflurane in 30% O2 were 48.3 +/- 4.9 mmHg and 47.2
      +/- 3.9 mmHg, respectively, and no significant difference was observed between
      the two values. Our results indicate that a decrease in PaO2 exerts no effect on
      PATCO2 at 0.7 MAC of enflurane anesthesia. This suggests that hypoxic stimulation
      does not play an important role in initiation of ventilation following
      posthyperventilation apnea at a light level of anesthesia.

PMID- 8301826
TI  - [Changes in plasma and urinary calcium levels during cardiopulmonary bypass].
AB  - Plasma total protein, total calcium, ionized calcium and urinary calcium were
      measured in six patients scheduled for open heart surgery, and the effect of the
      administration of calcium during and after cardiopulmonary bypass (CPB) was
      studied. After the initiation of CPB, plasma total protein decreased
      significantly from 5.47 +/- 0.50 g.dl-1 to 2.55 +/- 0.23 g.dl-1 (P < 0.01). Total
      calcium also decreased from 2.14 +/- 0.29 mmol.l-1 to 1.38 +/- 0.07 mmol.l-1 (P <
      0.01), and remained depressed during CPB. However, ionized calcium was not
      decreased and showed normal value during CPB because total protein concentration
      was decreased by hemodilution. Urinary calcium excretion increased gradually
      during CPB from 0.18 +/- 0.17 mmol.h-1 to 0.87 +/- 0.38 mmol.h-1 (P < 0.01) and
      the increase continued after CPB. Fractional excretion of filtered calcium
      increased from 0.85 +/- 0.63% to 54.16 +/- 36.52% (P < 0.05) accompanied with
      hypothermia. From these findings, reabsorption of the calcium in the kidney was
      thought to be inhibited by the influence of hypothermia at the early phases after
      weaning from CPB. When total protein returned to normal value after weaning from
      CPB, percentage of ionized calcium is predicted to diminish. We conclude that
      after weaning from CPB, administration of calcium is required because of the
      prolonged increase of urinary calcium excretion, particularly if blood containing
      citrate is given.

PMID- 8301827
TI  - [P50, 2,3-diphosphoglycerate and sodium as well as potassium in red blood cells
      in the perioperative period after hemodilutional autotransfusion].
AB  - The changes of the P50, 2,3-DPG and sodium as well as potassium of red blood
      cells in perioperative period were studied in 12 patients who underwent
      hemodilutional autotransfusion (HAT). P50 and 2, 3-DPG did not show remarkable
      changes before the third day after operation, but increased significantly on 5th
      and 7th day. There was a positive correlation between P50 and 2,3-DPG. Potassium
      of red blood cell increased significantly except on the first day. But sodium of
      red blood cell showed no remarkable change. In conclusion, our data demonstrate
      that the tissue oxygen supply from the red blood cell is maintained, because P50
      did not decrease. Sodium in the red blood cell does not show remarkable changes,
      and therefore the membrane function of the red blood cell should be kept intact.

PMID- 8301828
TI  - [Serum nitroglycerin concentrations during extracorporeal circulation with a
      membrane oxygenator incorporated with a cardiopulmonary bypass circuit].
AB  - The effect of a cardiopulmonary bypass circuit (CPB) on serum nitroglycerin (TNG)
      concentrations was studied in eight patients scheduled for cardiac surgery. The
      CPB consisted of polyvinyl chloride tubes and polypropyrene membrane oxygenator.
      TNG was administered intravenously at a rate of 1 microgram.kg-1.min-1 after
      induction of anesthesia. Blood samples were obtained from the radial artery,
      central vein, venous inlet of the CPB, and arterial outlet of the CPB. No
      significant difference in serum TNG concentration was found between the venous
      inlet of the CPB and arterial outlet of the CPB. Serum TNG concentration tended
      to increase during complete extracorporeal circulation. This suggests that the
      hypothermic inhibition of TNG metabolism may be greater than the adsorption of
      TNG by the CPB.

PMID- 8301830
TI  - [Changes in the blood flow in celiac artery and superior mesenteric artery after
      stellate ganglion block].
AB  - We evaluated the effect of stellate ganglion block (SGB) on the blood flow of
      celiac artery (CA) and superior mesenteric artery (SMA) by using the ultrasonic
      pulse Doppler technique. The subjects were 15 healthy volunteers (14 males, one
      female; average 26 years old; 22-38). Right C7-SGB was performed using 5 ml of 1%
      mepivacaine at the 7th cervical process. Blood pressure, heart rate, mean blood
      flow velocity and diameter in CA and SMA, were measured after 5 minute rest,
      before and after SGB. To measure the flow velocity and the diameter of vessels,
      ultrasonic diagnostic equipment SSA-270A or SSA-260A (Thoshiba CO, Ltd.) with
      convex electric-phased 3.75 MHz, probe was used. Doppler shiftgrams of the CA and
      SMA were recorded. Then, we calculated their flow volume and sectional area of
      vessels. In CA mean blood flow velocity tended to decrease (P < 0.05) and both
      flow volume and sectional area of vessels tended to increase (P < 0.001). In SMA,
      mean flow velocity tended to decrease (P < 0.05) and sectional area increased (P
      < 0.001). But flow volume did not show significant change. Our results indicate
      that right C7-SGB leads to an increase in the blood flow of CA.

PMID- 8301829
TI  - [Clinical study on intraoperative hyperketonemia in non-diabetic surgical
      patients under general anesthesia].
AB  - We measured plasma 3-hydroxybutyrate (3-OHBA) concentrations in 925 non-diabetic
      surgical patients who underwent various surgical procedures under various types
      of general anesthesia. Lactated Ringer's solution only was used as an
      intraoperative fluid. Among them, 46 patients (4.9%) developed high 3-OHBA levels
      of over 500 microM.l-1 during surgery. The causes of observed hyperketonemia
      would be surgical stress and preoperative fasting irrespective of 8 types of
      general anesthesia. Blood glucose, lactic acid, base excess and pH were not
      influenced by hyperketonemia. Prolonged recovery from anesthesia was not observed
      in any patients with hyperketonemia. Without any specific treatments, plasma 3
      OHBA levels were unchanged or rather decreased in 70% of the patients whose 3
      OHBA levels were over 500 microM. The results suggest that hyperketonemia below
      500 microM.l-1 is not always disadvantageous in nondiabetic patients under
      general anesthesia.

PMID- 8301831
TI  - [Resuscitation from experimentally induced hemorrhagic shock with hypertonic
      saline (effects on thoracic duct lymph flow and tissue oxygen tension)].
AB  - We compared the effect of hypertonic salt solution (7.2%, HS) with that of normal
      saline (NS) and lactated Ringer's solution (LR) for the treatment of hemorrhagic
      shock. We monitored hemodynamic parameters, thoracic duct lymph flow, and tissue
      oxygen tension over 3 hours after hemorrhage. Twenty-seven anesthetized mongrel
      dogs (0.5% halothane) were bled to an aortic pressure of 60 mmHg for 90 min
      following 40 mmHg for 30 min and then they were resuscitated with each solution.
      In NS group, the volume transfused was twice the bled volume, and in other two
      groups, each solution was transfused providing equal amounts of sodium as NS
      group. We found that hemodynamics were restored in HS group as well as in other
      two groups. On the other hand, thoracic duct lymph flow and tissue oxygen tension
      of renal cortex and liver increased significantly over other two groups. We
      conclude that small volume resuscitation with 7.2% NaCl may be effective in the
      initial treatment of hemorrhagic shock from the view of tissue circulation in
      vital organs.

PMID- 8301832
TI  - [In vitro effects of anesthetics on hydrogen peroxide generating system of the
      thyroid gland].
AB  - Effects of anesthetics on thyroidal hydrogen peroxide generating system was
      studied using porcine thyroid follicles. This system is indispensable in thyroid
      hormone synthesis and seems also to play an important role in regulation of
      thyroid hormone release. The results indicated that H2O2 generation was
      controlled by Ca2+ ion mobilization and protein kinase-C linked signal
      transduction system. It was also demonstrated that thiopental, halothane, and
      enflurane had inhibitory effects on H2O2 generation system in thyroid follicle
      cells, and 50% inhibitory concentrations (IC50) of each anesthetic drug were 60
      microM, 2.5% and 4.0%, respectively. Other anesthetic agents, such as local
      anesthetics and major tranquilizers did not show any inhibitory effects on
      porcine thyroid peroxidase activity as well as on the regulation of thyroid
      hormone release. Other than inhaled anesthetic agents, thiopental only is thought
      to have an antithyroid effects in clinical situation.

PMID- 8301833
TI  - [Changes in hemodynamics and mixed venous oxygen saturation during intraoperative
      harvest of autologous platelet-rich plasma].
AB  - Intraoperative harvest and transfusion back of platelet-rich plasma (PRP) are an
      effective procedure to decrease the requirement of blood transfusion. We selected
      the right atrium as the site for collection and transfusion back of the blood for
      the harvest of PRP. We studied changes of the hemodynamics and mixed venous
      oxygen saturation (SvO2 during the intraoperative harvest of autologous PRP in
      two patients who were undergoing cardiopulmonary bypass (CPB) surgery. The whole
      blood was collected, processed and the red blood cells were transfused
      immediately back to the patients using the Plasma Collection System (Haemonetics
      Model 50). The procedure was accomplished prior to starting CPB. The PRP product
      was transfused back into the patients at the completion of CPB. The arterial
      blood pressure, cardiac output, and SvO2 decreased during the collecting phase
      and immediately returned to the baseline values during the returning phase. No
      change was observed in the heart rate and arterial oxygen saturation. We conclude
      that the usage of right atrium as the site for collection and transfusion back of
      the blood to harvest PRP is effective and useful, and the continuous monitoring
      of SvO2 is mandatory for detecting the decline of the cardiac output.

PMID- 8301834
TI  - [Nonspecific anaphylactoid reaction in low IgE patients].
AB  - We reported two cases of anaphylactoid reaction caused by ranitidine and
      alprostadil. We suggest that these anaphylactoid reactions are nonspecific
      reactions which are observed in low IgE patients, because plasma IgE was still
      low 6 weeks after allergic reaction and these drugs have not been given to them
      before and eosinophilic and basophilic cells showed no change at all. We have to
      consider that there is a high risk of allergic reaction during general
      anesthesia, because many drugs are injected intravenously during general
      anesthesia.

PMID- 8301835
TI  - [Echocardiographic observation of intraoperative circulatory collapse in a
      patient with hypertrophic obstructive cardiomyopathy].
AB  - Two-dimensional Doppler echocardiography was used as an intraoperative cardiac
      function monitor in anesthetic management of a 79-year-old male with hypertrophic
      obstructive cardiomyopathy (HOCM) who underwent pulmonary lobectomy for lung
      cancer. Circulatory collapse occurred after thoracic epidural anesthesia (TEA),
      and was aggravated with following induction of general anesthesia. The collapse
      did not improve with phenylephrine nor atropine and necessitated ethylephrine and
      dopamine. During the above course, left ventricular outflow tract pressure
      gradient measured with continuous wave Doppler method was almost in proportion to
      cardiac output measured with thermo-dilution method. This means that TEA and the
      administration of inotropics did not worsen the left ventricular outflow tract
      obstruction. Left ventricular filling property estimated by trans-mitral flow
      velocity spectra improved when hemodynamics was stabilized with continuous
      infusion of dopamine, while it had been impaired during preoperative period and
      at the beginning of anesthesia. Our observation suggests that TEA for HOCM
      patient is a relative indication because it may exert negative inotropic effect,
      and that careful titration with inotropics is not contraindicated when undesired
      cardiac depression is proved by echocardiography.

PMID- 8301836
TI  - [Anesthetic management for cesarean section in two parturients with quintuplet
      gestation].
AB  - Two parturients with quintuplet pregnancy underwent urgent or elective cesarean
      section under general anesthesia at 30 and 29 week gestational ages respectively.
      Since multiple gestation pregnancy requires enough medical staffs and instruments
      for preterm newborn resuscitation, emergency cesarean delivery was avoided. For
      cesarean delivery, the operation was started immediately after crash induction
      and intubation, and less than 1% isoflurane balanced with 60% nitrous oxide was
      used before birth in attempt to maintain uterine relaxation and sufficient utero
      placental perfusion. After the delivery, aggressive maneuvers with PGE1 infusion,
      intravenous ergometrine and oxytocin, and interruption of volatile anesthetic
      inhalation (replaced by buprenorphine) were employed for decreasing the blood
      loss. The anesthesia and postoperative course of two patients and their babies
      were uneventful. Thus, anesthetic considerations may include; 1) high risk
      pregnancy related with huge pregnant uterus, 2) preterm labor, 3) preparation of
      sufficient man-power and instruments, 4) to avoid uterine contraction before
      delivery for fetal oxygenation, and 5) the puerperal promotion of uterine
      contraction to decrease blood loss.

PMID- 8301837
TI  - [Anesthetic management of a patient with acute intermittent porphyria].
AB  - A 40-y-o female was scheduled for modified radical hysterectomy and pelvic
      lymphadenotomy for malignant ovarian tumor. Her past history revealed frequent
      episodes of reddish discoloration of her urine after physical strain. Her blood
      and urine samples were submitted for chemical analysis of metabolites of
      hemoglobin and porphyrin on suspicion of acute intermittent porphyria (AIP).
      Since these examinations took some days, the patient had to undergo the operation
      before the results arrived. To prevent an acute exacerbation of possible AIP,
      some anesthetic drugs had to be avoided. After premedication with atropine 0.5 mg
      IM, the patient had an epidural catheter placed for later use. General anesthesia
      was induced with intravenous fentanyl 0.3 mg IV, and inhalation of sevoflurane
      (0.5-4%) in nitrous oxide and oxygen by mask to eliminate psychological stress
      during the operation. Then, 0.5% bupivacaine was used through the epidural
      catheter to block the afferent physical stimulation from the lower half the body.
      Special attention was paid to stabilize the cardiovascular system. Color of the
      urine was carefully monitored with a densitometer to find out any early sign of a
      relapse of AIP during the operation. After the operation, reddish urine and rapid
      respiration suggested a possible exacerbation of AIP. Fluid therapy with glucose,
      sedation with chlorpromazine IV and an epidural infusion of buprenorphine (0.5
      mg) were performed. The urine became clear several days after the operation and
      the postoperative course was uneventful. Anesthetic management of patients with
      AIP is discussed along with the introduction of pertinent literatures.

PMID- 8301838
TI  - [Anesthetic management of a patient with juvenile hyaline fibromatosis: a case
      report].
AB  - Juvenile hyaline fibromatosis (JHF) is a rare disease of autosomal recessive
      heredity characterized by multiple subcutaneous nodules, hypertrophy of the
      gingiva, and flexural contracture of the joints including those of the cervical
      vertebrae and the mandibula. It has been pointed out that the clinical features
      render tracheal intubation profoundly difficult. We present a case of 6-year-old
      girl diagnosed as JHF and anesthetized for tumor resection and reconstruction of
      the naso-oral region. She was significantly small for her age weight 12.3 kg and
      lived on a wheel-chair because of flexion contracture of the extremities.
      However, the cervical spinal joints were not involved and the neck could be
      extended in our case. With extreme care and preparation, anesthetic induction and
      tracheal intubation were smoothly done although a tooth was damaged by the
      surgeon when gauze-packing was attempted into the pharynx before the operation.
      Anesthesia was maintained uneventfully and satisfactorily during the surgery
      under anesthesia with nitrous oxide, oxygen, sevoflurane, fentanyl and
      vecuronium. There was no prolongation of nor abnormal reaction to the effect of
      vecuronium observed in this patient.

PMID- 8301839
TI  - [A new departure of an incorporated round visits; anesthesiologists and
      pharmacists ].
AB  - We commenced a new trial of an incorporated round visit. Members of round visit
      are 4 anesthesiologists and 2 pharmaceutists. This new trial gives us the
      following advantages; 1. We can get the newest drug informations at bed side
      during the round visit. 2. We can select a more reasonable therapy for patients
      through discussions. 3. Cooperative development of clinical studies concerning a
      new model or style of drugs may be possible. This new style of round visit is
      also of benefit for patients because it leads to administration of more pertinent
      drugs. We recommend to have a chance of cooperation between anesthesiologists and
      pharmaceutists in other hospitals.

PMID- 8301840
TI  - Long-term prognosis in 990 medically treated Japanese patients with coronary
      artery disease.
AB  - We performed a retrospective analysis of the fate of 990 medically treated
      Japanese patients with coronary artery disease. Patients were enrolled in this
      study between September 1973 and February 1984. They were confirmed to have
      significant coronary artery disease by coronary angiography. There were 924 males
      and 66 females with a mean age of 54.4 years. The mean duration of follow-up was
      9.4 years with a range of 6.5 to 17.0 years. The 5-year and 10-year survival
      rates for the entire population were 92.1% and 84.4%. The 5-year and 10-year
      survival rates in patients with single- (SVD), double- (DVD), and triple-vessel
      disease (TVD) and left main trunk (LMT) disease were as follows: 96.0% and 91.9%
      for SVD, 93.8% and 87.5% for DVD, 83.2% and 68.3% for TVD, and 89.3% and 84.6%
      for LMT disease. This was the first large follow-up study of coronary artery
      disease in Japan. Its results suggest that the prognosis of Japanese patients
      with coronary artery disease is more favorable than that of patients in Western
      countries. In addition, the findings should provide a control data base for
      future studies in Japan and the West.

PMID- 8301841
TI  - Glutathione peroxidase activity in serum during acute myocardial infarction and
      unstable angina pectoris.
AB  - We studied GSH-Px enzyme activity in serum after acute myocardial infarction
      (AMI) and unstable angina pectoris (UAP). The study included 15 patients with AMI
      and 9 patients with UAP. Serum GSH-Px activity in the AMI group (0.992 +/- 0.071)
      (IU/ml) was higher than that of the UAP group. Serum GSH-Px activity was
      established as 0.683 +/- 0.110 (IU/ml) in UAP and 1.012 +/- 0.121 (IU/ml) in 10
      healthy subjects (p < 0.0005). We suggest that measurement of serum GSH-Px
      activity together with other enzyme tests such as CK-MB, LDH, GOT, etc. can be
      helpful in the differentiation of AMI from UAP.

PMID- 8301842
TI  - Safety and efficacy of amlodipine. A new once-daily calcium antagonist in non
      hypertensive patients with coronary artery disease.
AB  - To analyze the effects of the treatment of 5 mg amlodipine on blood pressure and
      heart rate with a 24-hour ambulatory blood pressure monitoring device and to
      evaluate its antiischemic efficacy using treadmill exercise testing, 7 non
      hypertensive patients with coronary artery disease were studied. The systolic and
      diastolic blood pressure and heart rate recorded over the entire day and during
      daytime did not change significantly after the treatment. On the other hand, the
      systolic blood pressure decreased significantly at night (122 +/- 19-->113 +/- 17
      mmHg, p < 0.05) after treatment, but the change can be considered to be within
      the physiological range. Exercise duration increased significantly after the
      administration of amlodipine (9.7 +/- 4.8-->11.1 +/- 4.9 min, p < 0.05). Systolic
      blood pressure, heart rate and rate-pressure product decreased significantly and
      in addition, ST segment depression was significantly less marked (-0.25 +/- 0.09-
      >-0.21 +/- 0.09 mV, p < 0.05) after treatment, when compared at the same level of
      work load. Therefore, the new once-daily calcium antagonist amlodipine is safe
      and efficacious in non-hypertensive patients with coronary artery disease.

PMID- 8301843
TI  - Mortality in relation to Minnesota code items in elderly subjects. Sex-related
      differences in a cardiovascular study in the elderly.
AB  - The prognostic value of electrocardiographic abnormalities has not been widely
      studied in the elderly. We examined the Minnesota code ECG items in 2254 elderly
      subjects of the Cardiovascular Study in the Elderly (CASTEL), performed on an
      Italian general population. In our experience, codes for ischaemia, 1st-degree
      atrio-ventricular block, bundle branch blocks, myocardial infarction, atrial
      fibrillation or sinus tachycardia were predictors of overall mortality in
      females, while only the former three items were predictors in men. Although
      ischaemia, left bundle branch block and atrial fibrillation were predictors of
      cardiovascular mortality in both sexes, right bundle branch block,
      supraventricular arrhythmias and left ventricular hypertrophy were predictors
      only in men, and 1st-degree atrio-ventricular block were predictors only in
      women. Surprisingly, left anterior haemiblock and bifascicular blocks were not
      predictive of mortality.

PMID- 8301844
TI  - Assessment of left ventricular diastolic function and potential by quantitative
      analysis of left ventricular filling curves in patients with atrial fibrillation.
      A new algorithm for Doppler echocardiographic study.
AB  - To evaluate left ventricular (LV) diastolic function and potential, LV filling
      curves for 18 patients with atrial fibrillation (Af) were constructed and their
      positions and appearance were evaluated quantitatively by analysis of 95% maximal
      filling volume points and maximal curvature alteration points. The LV filling
      curves of group A (Af only) lay left superiorly, while those of group B (impaired
      LV diastolic function) were situated right inferiorly, all bending steeply. The
      LV filling curves of group C (mitral stenosis) bent slightly. The lowest normal
      filling volume points and compensation areas were calculated to evaluate LV
      diastolic function and were demonstrated to be very different in groups A and B.
      The lowest normal filling volume points of group C were similar to those of group
      A, but compensation areas were smaller, indicating a lower LV diastolic
      potential. It is concluded that the 95% maximal filling volume point, maximal
      curvature alteration point, lowest normal filling volume point and compensation
      area are effective indices for evaluating not only LV diastolic function but also
      the diastolic potential.

PMID- 8301845
TI  - Effects of diabetes on lipid peroxidation and scavenger activity in
      ischemia/reperfusion injury.
AB  - This study examined the effects of ischemia/reperfusion on cardiac function and
      diabetes-associated lipid peroxidation and scavenger induction in isolated
      working hearts. Cardiac function in diabetic rats was depressed in proportion to
      the duration of diabetes. Plasma levels of malondialdehyde (MDA) were increased
      significantly after diabetes of 1-week duration (1wD). MDA levels in the
      myocardium were increased significantly after 4-weeks (4wD) and tissue superoxide
      dismutase (SOD) activity was also elevated significantly in 8-week diabetic rats
      (8wD) as compared to control values. In both controls and diabetics, tissue MDA
      concentrations increased significantly during the first 3 min of reperfusion
      following 20 min of ischemia, compared with preischemia levels. At the end of
      reperfusion, tissue MDA levels decreased in controls and 1wD hearts, but remained
      elevated in the 4wD and 8wD cases. The SOD activity in 8wD hearts decreased
      significantly after 20 min of global ischemia followed by 30 min reperfusion,
      compared with preischemia levels. By contrast, there were no significant
      differences between preischemic and after-reperfusion data for parameters of
      cardiac function in 8wD rats. Thus, lipid peroxidation appears to have little
      influence on cardiac function during ischemia/reperfusion in rats with chronic
      diabetes.

PMID- 8301846
TI  - Ca2+ sensitivity of contractile machinery and Ca2+ handling energy. Simulation.
AB  - Myocardial Ca2+ handling during excitation-contraction coupling has been modelled
      mathematically to gain a better insight into the expectation that Ca2+
      sensitization of contractile machinery may save myocardial energy utilization for
      Ca2+ handling. The basic model of myocardial Ca2+ kinetics and mechanoenergetics
      involved the sarcoplasmic reticulum (SR), sarcoplasm, troponin C (Tn) and
      crossbridges (CB). The relations among the released Ca2+ ions from the SR, peak
      concentrations of sarcoplasmic free Ca2+ ([Ca2+]i) and Ca(2+)-bound troponin
      ([TnCa]) and peak contractile force were computed, based upon the assumptions
      that the released Ca2+ ions diffuse as free Ca2+ in sarcoplasm, bind kinetically
      with Tn with an association rate constant of k1, dissociate from TnCa with a
      dissociation rate constant of k2, and are sequestered into the SR with
      consumption of ATP. TnCa was associated with CB cycling to develop force with a
      set of given on and off rate constants. The association constant Ka (= k1/k2) of
      TnCa as an index of Ca2+ sensitivity of Tn was varied 32-fold from 0.25 to
      8/microM. Results showed that Ca2+ sensitization from a lower Ka level could most
      sharply decrease the total Ca2+ release required to develop the same contractile
      force. Thus, it would reduce the total Ca2+ handling energy that the SR uses to
      maintain the same contractility.

PMID- 8301848
TI  - Coronary spasm as a cause of coronary thrombosis and myocardial infarction.
AB  - A 63-year-old man with an acute anterior myocardial infarction demonstrated an
      intracoronary nonocclusive thrombus distal to the organic stenosis of the left
      anterior descending coronary artery. One month after the infarction the thrombus
      was completely dissolved, and spontaneous and provoked spasm occurred overlying
      the organic stenosis of the coronary artery. Thus coronary spasm superimposed on
      the atherosclerotic stenosis was suggested as a cause of the thrombus formation
      that led to myocardial infarction.

PMID- 8301847
TI  - Correlation between metabolic and histopathological changes in the myocardium of
      the KK mouse. Effect of diltiazem on the diabetic heart.
AB  - Serial changes in myocardial parameters related to non-insulin-dependent diabetes
      mellitus were investigated in DDY mice (control), untreated KK mice, and KK mice
      treated with diltiazem (150 micrograms/kg body weight, KKd1: or 300 micrograms/kg
      body weight diltiazem, KKd2). The isozyme ratio of lactate dehydrogenase (LDH)
      [(LDH1+LDH2)/(LDH4+LDH5)] was used as an index of aerobic metabolism of
      myocardial tissue. Mean blood sugar levels did not vary between 5 weeks and 30
      weeks of age, ranging from 108 (range 60-198) mg/dl in DDY mice to 170 (range 110
      282) mg/dl in KK mice. The ratio of heart weight to body weight was larger in KK
      mice than in DDY mice at 20 weeks of age, but was unaffected by diltiazem
      treatment. The LDH isozyme ratio showed that DDY mice were in an aerobic state at
      15 and 20 weeks of age, while KK mice were in an anaerobic state at 10 and 15
      weeks of age. The KKd1 and KKd2 groups exhibited the same LDH isozyme ratios as
      untreated KK mice; diltiazem had no effect on the LDH isozyme ratio at 20 and 30
      weeks of age. The mean diameter of myocytes was increased in KK mice but
      diltiazem had no effect on this parameter. Interstitial fibrotic changes appeared
      at 15 weeks in untreated KK mice and progressed with age. These changes were
      completely suppressed in KK mice treated with diltiazem. These results suggest
      that hyperglycemia induces an anaerobic state in heart muscle, leading to muscle
      hypertrophy, degeneration, and fibrosis and that calcium antagonists may suppress
      these pathological changes.

PMID- 8301849
TI  - Coronary perforation to the left ventricular cavity by a guide wire during
      coronary angioplasty.
AB  - We describe a case in which the guide wire penetrated through the left anterior
      descending artery into the left ventricular cavity during percutaneous
      transluminal coronary angioplasty. This complication of coronary angioplasty
      which had not been previously reported was suspected because of the
      characteristic motion of the guide wire on the X-ray image and was confirmed by
      echocardiography.

PMID- 8301850
TI  - Spontaneous left anterior descending coronary artery dissection. Case report
      presentation and review of the relevant literature.
AB  - Spontaneous coronary artery dissection is a rare incident occurring usually in
      young patients, predominantly in females. It is usually fatal and found
      postmortem. We present the case of a middle aged man with spontaneous left
      anterior descending coronary artery dissection found angiographically which
      caused an anterior wall myocardial infarction. We also briefly review the
      relevant literature.

PMID- 8301851
TI  - Williams syndrome. A middle-aged case of markedly delayed diagnosis.
AB  - A rare case of Williams syndrome diagnosed at the age of 41 is documented. The
      first subjective symptom was chest pain and the patient displayed many other
      features in addition to severe supravalvular aortic stenosis with a systolic
      gradient of 60 mmHg. The stenotic lesion had an area of 0.5 cm2, and was
      associated with dilated and tortuous coronary arteries. Extended aortoplasty was
      successfully performed and the postoperative course has been excellent without
      any cardiac symptoms. In spite of the severe cardiac lesions, this case had been
      largely asymptomatic and presented unusual features related to the diagnosis and
      management of this syndrome in an adult. The pattern of abnormalities found in
      this case suggested problems in relation to the calcitonin/calcitonin gene
      related peptide (CGRP) and the elastin gene occurring in embryonic organogenesis.

PMID- 8301852
TI  - A case of idiopathic ventricular fibrillation with incomplete right bundle branch
      block and persistent ST segment elevation.
AB  - We report the case of a 42-year-old male who suffered from ventricular
      fibrillation (VF) without obvious QT prolongation. His electrocardiogram showed
      incomplete right bundle branch block (IRBBB) and persistent ST segment elevation
      in the right precordial leads during sinus rhythm. Cardiac catheterization
      revealed no overt heart disease except moderate endocardial and subendocardial
      fibrosis in the left ventricle. Mental stress seemed to trigger VF, and ST
      elevation became prominent just before VF. Propranolol and mexiletine have been
      effective in preventing VF for over 3 years.

PMID- 8301853
TI  - Primary angiosarcoma of the heart. Report of a case and review of the literature.
AB  - We report on a 44-year-old male with primary cardiac angiosarcoma who died 11
      months after onset of nonspecific symptoms (thoracic pain and general fatigue) of
      intracerebral metastases. A right atrial tumor mass and a pericardial effusion
      could be demonstrated by transthoracic and transesophageal echocardiography.
      Cardiac angiography showed a right atrial hemangioma, fed by the right coronary
      artery. In a review of 108 cases of primary cardiac angiosarcoma we summarize
      clinical features, diagnostic means, therapeutic approaches and life expectancy
      of this rare disease.

PMID- 8301854
TI  - [Reliability and validity of a Japanese version of the Dementia Behavior
      Disturbance Scale].
AB  - Since behavioral disturbance among patients with dementia is a great burden for
      their caregivers, quantification of behavioral disturbance is essential in
      determining disease severity and assessing the impact of the disease on
      caregivers. However, the method of its quantification for objective assessment is
      not established yet. We studied the reliability and validity of a Japanese
      version of the Dementia Behavior Disturbance Scale (DBD Scale) which was
      originally developed by Baumgarten et al. We also studied the relationship
      between DBD scores and the degree of burden felt by caregivers. Our subjects
      consisted of 27 cases with dementia (mean age 77.7 years), and 17 cases of
      patients with neurological disorders without dementia (76.8 years), and 10
      institutionalized patients with dementia (82.3 years). The test-retest
      reliability, internal consistency, and inter-rater reliability were very good;
      the coefficient of correlation between DBD scores at the two interviews was 0.96,
      the coefficient of internal consistency was 0.95, and the intraclass correlation
      coefficient was 0.71 +/- 0.10. DBD scores correlated significantly with SPMSQ
      errors and caregivers' burden; r = 0.54 and 0.53, respectively. Our results
      indicate that the DBD Scale is highly reliable, and may be useful for objective
      assessment of behavioral disturbance and caregivers' burden.

PMID- 8301855
TI  - [The relation between blood pressure variation and daily physical activity in
      early morning surge in blood pressure].
AB  - Morning rise in blood pressure (morning surge; MS) has been shown to be
      associated with the occurrence of myocardial ischemic events and stroke. This
      study aimed to elucidate the incidence and the mechanism of MS in hypertensive
      patients (HT). We monitored ambulatory blood pressure (BP) and physical activity
      in 68 untreated HTs using TM2421 (A & D Co. Ltd.) and ACTIVETRACER (GMS Ltd.) for
      detection of MS. MS was defined as a rise in BP > 50 mmHg (90% tile of 35
      normotensives) during early morning (4:00 to 9:00 A.M.) compared with the lowest
      basal BP at night. MS was seen in 41 patients (52.6%) and was classified into two
      groups; MS1: BP rose steeply after waking up (27 patients) and MS2: BP started to
      rise gradually during sleep (14 patients). The mean age of MS1 was significantly
      higher than that of MS2 (72 vs. 62 years, p < 0.01). BP reached its basal value
      earlier in MS2 than in MS1 at night though the basal BP values were comparable
      between the two groups. Mean 24-hour BP and physical activity were similar
      between the two groups, though significantly higher incidence of cases with a
      correlation between SBP and activity was seen in MS1. In conclusion, there are
      two types of MS, the mechanisms of which may differ. MS occurring immediately
      after waking up was more common in older HTs, and possibly was related to
      augmented arousal response in BP, while MS beginning gradually during sleep was
      more common in younger HTs and was characterized by reaching basal BP earlier at
      night.

PMID- 8301856
TI  - [Natural history and URSO dissolution therapy of gallbladder stones in the
      elderly].
AB  - To determine how to treat silent gallstones in the elderly, 1771 autopsied cases
      65 years of age or older were studied retrospectively, and 121 cases with
      asymptomatic gallbladder stones were followed for over 3 years. Of these, 47
      cases treated with ursodeoxycholic acid (UDC) for over 3 years were investigated
      to determine the efficacy of UDC therapy. In the autopsied cases, the incidence
      of gallbladder stones was 16%, and increased with age. The ratio of males to
      females was 1:1.2. Only 3.2% of people with silent gallstones developed symptoms.
      Autopsy studies showed that the majority of people with gallstones died of
      unrelated causes such as benign respiratory and circulatory diseases. Only 1.8%
      of patients with gallstones died of acute cholecystitis or gallbladder carcinoma.
      UDC treatment was effective in 55.9% of patients with radiolucent stones. The
      percentage of patients requiring surgery due to becoming symptomatic was much
      lower (6.4%) in UDC-treated patients. The visualization of the gallbladder on
      cholecystogram improved in cases treated with UDC. These results indicate that
      elderly patients with silent gallstones generally develop neither symptoms nor
      carcinoma. Therefore, follow-up management by ultrasonography and
      cholecystography can be allowed. We also emphasized that a satisfactory response
      was obtained with long term UDC therapy.

PMID- 8301857
TI  - [Abnormality of bone mineral metabolism in elderly female patients with
      dementia].
AB  - In order to clarify the relationship between dementia and osteoporosis, bone
      mineral metabolism was studied in elderly female patients with dementia. We
      measured bone mineral densities of the vertebral body and the femoral neck using
      DEXA, and evaluated Ca-related factors in 22 patients with dementia of the
      Alzheimer type (DAT), 23 patients with vascular dementia (VD), and 22 age-matched
      controls (C). Activity of daily living was significantly poorer in VD patients
      than controls, but no difference was shown between DAT and C groups. Bone mineral
      density values of the vertebral body and the femoral neck were significantly
      decreased in both DAT and VD groups when compared to C group. DAT patients showed
      significant decreases in serum Ca and Ca2+ ion, increase in serum parathyroid
      hormone, and decrease in serum 1,25-dihydroxyvitamin D, a tendency towards
      decrease in serum calcitonin, and a tendency towards increase in urinary Ca.
      However, VD patients showed only significant increase in urinary Ca and a
      tendency towards decrease in serum 1,2-dihydroxyvitamin D, without showing other
      changes of Ca-regulating hormones. These results suggest that patients with
      dementia are more often associated with osteoporosis, and that in DAT several
      abnormalities of Ca-regulating factors play an important role in the development
      of osteoporosis, while in VD limited physical activities contribute to bone
      mineral loss.

PMID- 8301859
TI  - [Gastric ulcer and patterns of distribution of intestinal metaplasia in the
      elderly].
AB  - Gastric ulcer was studied with regard to the relationship with patterns of
      distribution of intestinal metaplasia (IM). 882 stomachs of elderly patients,
      obtained from autopsies from 1987 to 1991 were examined histopathologically.
      There were 74 open gastric ulcers and 88 ulcer scars. Distribution of IM was
      classified into 7 types. Open ulcers and scars were found more often in type O
      (IM found in the entire lesser curvature which is the most common type in the
      elderly) than in other types. Open ulcers in type O were mostly shallow and
      located in the IM area. Many open ulcers in type A (IM involving the antrum) and
      type B (IM involving both the antrum and cardia) were deep and on the boundary
      zone between the IM area and the proper gastric mucosa area. Most of the deep
      scars that did occur in type O were in the IM area but in types B and A most of
      them were located on the boundary zone. Scars in type O probably developed on the
      boundary zone when they were open ulcers and removed in the IM area because of
      progression of the IM area. In some cases ulcers were at the boundary zone of IM
      involving the cardia and this finding was characteristic of elderly cases.

PMID- 8301858
TI  - [Long-term follow-up study after permanent pacemaker implantation in patients
      aged 60 years or over with sick sinus syndrome].
AB  - Ninety-five patients aged 60 years or over with a permanent pacemaker implanted
      for sick sinus syndrome were divided into two groups: 32 patients with
      physiological pacing (group P) and 63 patients with ventricular pacing (group V).
      The mean follow-up period was 45.0 +/- 36.6 months in group P and 50.3 +/- 37.8
      months in group V. Paroxysmal atrial fibrillation (Af) occurred in 28% of group P
      and 71% of group V (p < 0.05). The incidence of stable Af was also lower in group
      P than in group V (9% vs. 30%, p < 0.05). None of group P with only
      bradyarrhythmia had stable Af. However, 6 of 21 patients (29%) in group V with
      bradyarrhythmia showed stable Af. There was no significant difference in stable
      Af between group P with bradycardia-tachycardia syndrome (BTS) and group V with
      BTS (19% vs. 31%). A lower incidence of embolic events was also observed in group
      P (3% vs. 25%, p < 0.05). Nine of 16 patients with embolic events in group V died
      of complications following embolism (8 patients; cerebral embolism, one patients:
      renal and superior mesenteric arterial embolism). The survival rates at 5 and 10
      years were 80% and 69%, respectively, for group P and 56% and 33% for group V (p
      < 0.01). Thus, with regard to permanent pacing for patients with sick sinus
      syndrome, physiological pacing should be selected for control of morbidity and
      total mortality.

PMID- 8301860
TI  - [A neuropathological study on axonal dystrophy in the gracile nucleus of an old
      Japanese monkey].
AB  - Ageing axonal dystrophy was studied electron microscopically in the gracile
      nucleus of a very old Japanese monkey (28 years of age) from the standpoint of
      comparative neuropathology. It was revealed that the Japanese monkey has
      characteristics different from albino rats concerning the ultrastructure of the
      dystrophic axonal spheroids. Spheroids in the former animal contained no traces
      of so-called layered loops of membrane nor coiled tubular rings etc. which have
      been interpreted in cases of albino rats and other animal species as
      morphological expression of secondary metamorphosis of primarily accumulated
      normal axoplasmic organelles at the presynaptic boutons. Instead, spheroids in
      the Japanese monkey contained dense homogeneous osmiophilic granules and
      screwnail-like filament crystalloids, which have not been found in other animal
      species including albino rats. These abnormal substructures were already present
      in the early stage of axonal dystrophy and tended to occupy a large volumetric
      proportion of gigantic spheroids. It was concluded that these substructures
      constitute essential components of formed spheroids in combination with smooth
      axoplasmic reticulum, and that they represent primary products of axonal
      dystrophy and not the secondary products of metamorphosis like coiled tubular
      rings or layered loops of membrane described above. The enormous accumulation of
      smooth axoplasmic reticulum in other animal species including albino rats is
      characterized by the formation of a dense tridimensional reticular network. In
      the Japanese monkey, this process is characterized by massive dense parallel
      aggregation of straightened tubules of apparently smooth axoplasmic reticular
      origin rather than by formation of tridimensional network.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8301861
TI  - [MRI study of the brain in aged volunteers: T2 high signal intensity lesions and
      high cortical function].
AB  - In order to characterize age-related and chronological changes of the brain,
      longitudinal studies of aged volunteers were conducted using computed tomography
      since 1982. The present paper discusses correlations between brain function and
      findings of MR images which were obtained a using 1.5 T superconductive MR
      instrument since 1989. A total of 118 volunteers aged 60 to 88 years old with a
      mean age of 75.0 +/- 6.7 participated in the study, which consisted of MRI, EEG
      recording, the Benton Visual Retention Test and a medical interview. Subjects
      with a past history or clinical evidence of CVD, head trauma or dementia were
      excluded from the study. Incidence of T2 high signal intensity lesions increased
      with age. Some showing T1 low signal intensity in the same lesion were considered
      to be lacunar infarction, over all incidence of which was 24.6%. Numbers of
      correct responses on the BVRT showed a negative correlation with numbers of T2
      high signal intensity lesions. Although the aged volunteers in the present study
      could achieve all activity of daily living without any trouble, high cortical
      function evaluated by visuoperceptual performance of BVRT was somewhat disturbed
      in participants with multiple T2 high signal intensity lesions. Brain atrophy
      seems to be more advanced in groups with T2 hyper intensity lesions than in the
      group without them. These findings may support the notion that T2 high signal
      intensity lesions are not merely an index of ageing but pathologic lesions
      accompanied with senescence, although further studies including
      clinicopathological correlation are necessary to establish this concept.

PMID- 8301862
TI  - Chronic depression of monopolar, endogenous type: with special reference to the
      premorbid personality, "Typus melancholicus".
AB  - We retrospectively examined 70 depressives, who first visited our outpatient
      clinic in 1989, agreed to our examination and met the criteria of major
      depression and melancholic type in DSM-III-R. Forty-nine recovered and 21 had a
      chronic course of a 2-year duration. Of the items examined in the multivariate
      analysis, a high total LE score, a long duration prior to entry and a high degree
      of "Typus melancholicus" greatly contributed to the chronicity in this order of
      magnitude. Age, severity at entry and sex contributed to it in relatively small
      degrees and familial loading of depression had almost no effect on the course.
      The relationship between the degree of "Typus melancholicus" and course of
      depression was discussed based on data.

PMID- 8301864
TI  - Depression and quality of life in the elderly in a special nursing home.
AB  - Using a Japanese version of the Self-Rating Depression Scale by Zung (SDS) and
      the Quality of Life (QOL) rating scale designed by Iida et al. (QOL scale), we
      compared the QOL and depressive state of special nursing home residents and the
      elderly in the general community. The QOL scale has four categories: physical
      functioning, emotional adjustment, interpersonal relationships and attitudes
      toward life. High scores in either examination indicate a greater impairment. The
      SDS scores of the residents in the special nursing home were significantly lower
      than those of the elderly in the community, but the scores in 3 categories and
      the total score, except for those of physical functioning of the QOL, were
      significantly higher in the nursing home residents. In the nondepressed elderly
      rated by the SDS, the physical functioning score of the elderly in the community
      significantly exceeded that of the special nursing home residents. In the
      depressed elderly, all the scores including the total score were significantly
      higher than those in the special nursing home residents. Our results suggest that
      while the QOL of the depressed elderly in a special nursing home was poorer than
      that of the elderly in the community, their depression could be treated. However,
      the QOL cannot be improved by treatment alone.

PMID- 8301863
TI  - Hebephrenia as the most prevalent subtype of schizophrenia in Japan.
AB  - The author reviewed the frequency of the hebephrenic subtype compared to the
      paranoid subtype diagnosis of schizophrenia in Japan, using research papers and
      statistical reports that have been published during this century. It was found
      that the reported rates for the hebephrenic subtype ranged from a low of 23% to a
      high of 68% with the majority falling between 30% and 50%. These rates had not
      varied significantly over a long period of time or across wide geographical
      areas. It was discussed that Japanese psychiatrists were so sensitive to the
      negative symptoms of schizophrenia that they had a broader concept of hebephrenia
      as compared to other Kraepelian subtypes in schizophrenia.

PMID- 8301865
TI  - Perceived rearing attitudes and minor psychiatric morbidity among Japanese
      adolescents.
AB  - The relationship between perceived rearing experiences and minor psychiatric
      morbidity was studied in a sample of Japanese adolescents. Their perceived
      rearing experiences were measured by the Parental Bonding Instrument (PBI) and
      minor psychiatric morbidity by the General Health Questionnaire (GHQ). The total
      GHQ score was slightly but significantly higher (r = 0.28) among those recording
      high maternal protection than among those with low maternal protection, but of
      the subscale scores of the GHQ, only the anxiety and insomnia subscale retained
      this same relationship with perceived rearing experiences. The parental age,
      educational career, and sibship position showed no correlation with the PBI
      scores.

PMID- 8301866
TI  - The application of WPSI to epilepsy patients.
AB  - Eighty-five epilepsy patients were questioned using the Washington Psychosocial
      Seizure Inventory (WPSI). It was confirmed that uncontrollable epilepsy patients
      had more severe psychosocial problems than other patients. WPSI was also useful
      in clinical work.

PMID- 8301867
TI  - Frontal lobe tumor associated with late-onset seizure and psychosis: a case
      report.
AB  - This is a report of a 55-year-old woman with a 6-year history of uncontrollable
      complex partial seizure and severe delusion. A computed tomography (CT) brain
      scan showed a nonenhanced low density area with an ill-defined mass located at
      the right frontal lobe. Magnetic resonance imaging (MRI) demonstrated an area of
      hyperintensity on T2-weighted images. After a tumorectomy, the patient gradually
      recovered from the seizures and delusion. A histological diagnosis showed a mixed
      oligoastrocytoma or dysembryoplastic neuroepithelial tumor (DNT). The clinical
      and pathological features of the tumor as well as its relation to psychosis were
      discussed.

PMID- 8301868
TI  - Characteristics of those who refuse to attend school in Fukuoka City: an analysis
      based on teachers' reports.
AB  - In 1988, we investigated the characteristics of children who refused to attend
      elementary and junior high schools in Fukuoka City, mainly from the viewpoint of
      their present status. The main results were as follows: Prevalence of school
      refusers in elementary schools (0.13%) was much higher in Fukuoka City than in
      all Japan, but almost similar in junior high schools (0.47%). About one-third of
      the school refusers didn't mind their absence so much, and more school refusers
      in junior high schools could not understand the significance of school
      attendance. These results suggest that school refusers, who may have a borderline
      personality organization, are likely to prevail.

PMID- 8301869
TI  - Object images of eating disorder patients.
AB  - The authors investigated images held by eating disorder patients toward selected
      stimulus words using the semantic differential method. The concept "object image"
      was introduced here to designate the images which any person has about the
      mother, the father, etc. A comparison was made between 22 eating disorder
      patients with concurrent borderline personality disorder, 20 patients without
      borderline pathology, and 48 controls. The eating disorder patients were found to
      have a "weaker" image of "motherliness" and "womanliness" compared to the control
      group. Another characteristic of eating disorder patients was their unfavorable
      image of children. The authors also studied the images held by fathers and
      mothers. In the families with borderline patients, the discrepancies between what
      we term "object images" held by fathers, mothers, and daughters were conspicuous.
      The importance of a tripartite (daughter-mother-father) relationship in the
      psychopathology of eating disorder is discussed.

PMID- 8301870
TI  - Long-term course of adult patients with delayed sleep phase syndrome.
AB  - A response to treatment and long-term course of 14 adults with delayed sleep
      phase syndrome were investigated with the use of their hospital records and
      mailed questionnaires. Six patients treated with chronotherapy showed full
      recovery just after the treatment. In three of them the delay of sleep phase
      relapsed one year afterwards. Four of five patients treated with pharmacotherapy
      alone showed partial recovery. Six of nine patients followed for periods of
      longer than three years after treatment showed good prognoses, though all of them
      still had a mild phase delay and had to shorten their sleep time in order to work
      full-time. The three others had poor prognoses and one of them was under
      psychiatric treatment for affective instability. These findings suggest that a
      long-term follow-up is needed to judge the effect of the treatment.

PMID- 8301871
TI  - Psychiatric liaison referral of elderly inpatient in a medical school hospital.
AB  - A retrospective study of elderly inpatient referral was carried out at Saga
      Medical School Hospital in order to assess the effectiveness of consultation
      liaison service. A total of 51 patients aged 65 and over were referred to the
      Psychiatric Department. Their referral rate, clinical characteristic, diagnosis
      and psychiatric recommendation were reviewed from the records. A comparison of
      various aspects concerning the referral for the periods before and after the
      installation of an effective psychiatric consultation-liaison service showed a
      mild change. The striking finding was that the referral rate increased
      significantly for male patients under 75 years of age.

PMID- 8301872
TI  - Difference of the 28-item general health questionnaire scores between Japanese
      high school and university students.
AB  - The General Health Questionnaire (GHQ) with 28 items was tested in Nagasaki city
      on 138 senior students in a prefectural high school and 685 freshmen in a
      national university to evaluate the degree of students' mental stress due to the
      highly competitive entrance examination for university. The average GHQ score
      tested on high school students was 5.33 for males and 7.07 for females, and 3.99
      for males and 4.42 for females on university students. It showed that high school
      students were under greater pressure than university students and female students
      were in a higher tension compared with male students. The factor analysis showed
      that the primary and secondary factor of high school students were "severe
      depression" and "anxiety and insomnia," while "somatic symptoms" were the primary
      factor causing stress in university students.

PMID- 8301873
TI  - Clinicopathological correlations of visual depth perception in patients with
      cerebrovascular disease.
AB  - Visual depth perception in 100 patients with cerebrovascular disease was
      evaluated using the Titumus stereotest. Twelve patients showed depth perception
      impairment. CT scans revealed that the lesion was located on the right hemisphere
      in 6 patients and on the left hemisphere in 3 patients, and that the remaining 3
      patients had multiple infarctions. 123I SPECT was performed in 7 patients with
      moderate to severe depth perception impairment, of whom 6 patients showed a
      reduced blood flow in the posterior half of both the right and left cerebral
      hemispheres. Moderate to severe impairment of depth perception was more
      frequently observed in patients with a lesion in the right hemisphere or in the
      posterior half of either hemisphere.

PMID- 8301874
TI  - Micturitional disturbance in multiple system atrophy.
AB  - Detailed micturitional histories and urodynamic studies were conducted to
      investigate the micturitional disturbance in multiple system atrophy (MSA).
      Eighty-six patients with MSA comprised of 14 with striatonigral degeneration
      (SND), 42 with olivopontocerebellar atrophy (OPCA) and 30 with Shy-Drager
      syndrome (SDS). The results were as follows. Micturitional symptoms were noted in
      over 90% of patients with each type of MSA. Dominant symptoms were irritative
      ones in SND and OPCA, and a combination of irritative and obstructive ones in
      SDS. Micturitional symptoms in SDS appeared earlier than those in SND or OPCA.
      The degree of micturitional disturbance was severer in SDS than in SND or OPCA.
      Micturitional disturbance tended to become worse as the disease progressed. The
      responsible sites of lesions of micturitional disturbance seemed to be supra- as
      well as infranuclear lesions of the pelvic and pudendal nerves in MSA.
      Infranuclear lesions were more prominent in SDS than in SND or OPCA. Follow-up
      studies of some of the patients with SDS and OPCA suggested that the responsible
      sites of pelvic nerve lesions changed from supra- to infranuclear lesions during
      the course of disease.

PMID- 8301875
TI  - Three-dimensional surface display using 123I-IMP in a case of motor neuron
      disease with dementia.
AB  - A case of motor neuron disease with dementia is presented. A brain CT showed
      atrophic changes mainly in the left frontal cortex, and 123I-IMP SPECT disclosed
      a decrease in 123I-IMP uptake in the frontal regions. To distinguish a subregion
      related to dementia from that related to motor system disorders, a three
      dimensional surface display with 123I-IMP was reconstructed. The imaging method
      clearly demonstrated cortical hypoperfusion in the inferomedial frontal cortex
      and the motor-sensory cortex. These findings suggest that dementia may be due to
      the former lesion and motor system disorders due to the latter lesion,
      respectively.

PMID- 8301876
TI  - Effects of TJ-960 on Sternberg's paradigm results in epileptic patients.
AB  - OBJECTIVES: This study is aimed at investigating the effects of TJ-960 on
      cognitive function in epileptic patients. Sternberg's paradigm was used to
      examine the change in cognitive function, especially short-term memory, resulting
      from administration of TJ-960, along with the effects of the drug on seizures.
      SUBJECTS: The subjects of this investigation were 26 epileptic outpatients (14
      males and 12 females; average age: 35 +/- 11 years old) of the Saitama Medical
      School Hospital, the Tokyo Medical and Dental University Hospital and the Tokyo
      University Hospital. The controls were 17 other epileptic outpatients (12 males
      and 5 females; average age: 40 +/- 12 years old) of the same hospitals. METHODS:
      The subjects were administered 7.5 g of TJ-960 per day for 8 weeks in addition to
      their previous medications. Immediately before the beginning of drug
      administration, and again after 8 weeks of administration, they were examined,
      using Sternberg's paradigm. The controls were examined at intervals of 8 weeks in
      the same manner as the subjects (i.e., no change in regimen). RESULTS: After 8
      weeks of treatment with TJ-960, 8 of the subjects exhibited a greater than 25%
      decrease in the number of seizures. Seventeen cases showed no change, and one
      case showed exacerbation. The correct reaction times for Sternberg's paradigm in
      the group administered TJ-960 were 955 +/- 307 ms at the time of the first
      examination and 881 +/- 277 ms at the time of the second, and those of the
      control group were 845 +/- 288 ms for the first examination and 829 +/- 269 ms
      for the second. As these figures show, the correct reaction time was
      significantly shortened between the first and second examinations in the TJ-960
      group. No change was exhibited in the sample reaction time between the first and
      second examination in either group. The difference in alpha wave power of the
      occipital region before and after the TJ-960 administration was significantly
      greater in the patients who showed improvement in Sternberg's paradigm as
      compared to the patients who remained unchanged in Sternberg's paradigm. In
      addition, the results for the theta wave power were opposite to those of alpha
      waves. As mentioned above, TJ-960 was presumed to have the effect of improving
      the cognitive function in epileptic patients.

PMID- 8301877
TI  - Myoclonus and seizures in a patient with parkinsonism: induction by levodopa and
      its confirmation on SEPs.
AB  - A 68-year-old woman with parkinsonism showed cortical myoclonus and seizures
      under antiparkinsonian medication. Myoclonus was induced and enhanced by L-dopa,
      developing into generalized seizures. EEG was abnormal and somatosensory-evoked
      potentials (SEPs) showed giant SEPs, transcortical reflex (C reflex) and jerk
      locked potentials. Myoclonus and seizures disappeared after discontinuation of L
      dopa and the introduction of valproate sodium (VPA). We described the occurrence
      of L-dopa-induced myoclonus and seizures in a case of parkinsonism with its SEPs
      findings.

PMID- 8301878
TI  - Effective clinical response at low plasma levels of haloperidol in Japanese
      schizophrenics with acute psychotic state.

PMID- 8301879
TI  - Concentration of neural thread protein in cerebrospinal fluid from progressive
      supranuclear palsy and Parkinson's disease.
AB  - We measured the concentration of neural thread protein (NTP) in cerebrospinal
      fluid (CSF) by an automatized microparticle enzyme immunoassay from 11
      progressive supranuclear palsy (PSP) patients and 11 Parkinson's disease (PD)
      patients and 7 patients with cervical spondylosis as controls. The mean levels
      did not differ significantly among the groups. In the PSP group, however, the
      levels correlated significantly with the severity of motor symptoms, signs and
      functional disability but not with dementia, while the opposite was true in the
      PD group. The elevated levels in PSP cases may reflect an increase with
      progression of the disease in such pathological structures as neurofibrillary
      tangles or neuropil threads, while in PD such levels may indicate associated
      Alzheimer-type pathology.

PMID- 8301880
TI  - MELAS without ragged red fibers or lactic acidosis diagnosed by mitochondrial DNA
      testing.
AB  - A case of mitochondrial encephalomyopathy with lactic acidosis, a stroke-like
      episode (MELAS) without ragged red fiber, diagnosed by mitochondrial DNA testing,
      is reported. A 37-year-old woman experienced a sudden and recurrent headache with
      vomiting and stroke-like episodes. Brain CT and MRI showed multiple infarction in
      the temporal lobes, not corresponding to artery distribution. However, the plasma
      levels of lactate and pyruvate were normal, and showed no increased after aerobic
      exercise. Biopsied muscle showed no evidence of ragged red fibers and deficient
      activity of mitochondrial enzymes in the respiratory chain. The final diagnosis
      was made by mitochondrial DNA testing. A southern blot analysis after Apa I
      digestion revealed the A-to-G mutation in the tRNA(Leu(UUR)), which is specific
      to MELAS.

PMID- 8301881
TI  - Effect of pravastatin on human sleep.
AB  - To evaluate the effect of pravastatin, an HMG-CoA reductase inhibitor, on sleep,
      the drug or a placebo was administered to 5 healthy adults for 16 days by the
      double-blind method. Pravastatin caused no changes in sleep parameters. This
      indicates that it had no effect on human sleep for the following possible
      reasons: Being hydrophilic, the drug does not readily cross the blood-brain
      barrier. It does not inhibit prostaglandin D2 synthase, a possible sleep-inducing
      substance. It was thought that a decrease in the total cholesterol level in the
      blood has no effect on sleep in healthy adults.

PMID- 8301882
TI  - Transient unilateral catalepsy and right parietal damage.
AB  - We describe the appearance of transient catalepsy of the left upper extremity in
      a patient without previous psychiatric illness after a right parietal subcortical
      hemorrhage. This case, and five other available cases in the relevant literature,
      demonstrates that catalepsy can be produced by right parietal damage.

PMID- 8301883
TI  - An autopsy case of coexisting portal systemic encephalopathy and senile dementia
      of the Alzheimer type.
AB  - An autopsy case of portal systemic encephalopathy and senile dementia of the
      Alzheimer type coexisting in a 77-year-old man is described. The patient had
      suffered recurrent episodes of delirium after a subtotal gastrectomy for gastric
      carcinoma. He died of DIC 45 months after the gastrectomy. A pathological
      examination revealed a vascular plexus around the liver which might have served
      as collateral circulation. Neuropathologically, spongy necrosis and Alzheimer
      type II changes of astrocytes were found in the basal ganglia and fronto
      occipital cortices. In the same anatomical regions, only immunohistological
      staining using antibody against amyloid beta-protein and the periodic-acid
      methenamine silver method revealed abundant neuriticplaques, cerebral amyloid
      angiopathy and diffuse plaques. We discussed the clinicopathological findings in
      this case.

PMID- 8301884
TI  - Classification of senile plaques by three-dimensional analysis.
AB  - We evaluated the number of each senile plaque subtype in Alzheimer's brain by the
      usual two-dimensional analysis using a single, methenamine silver stained section
      and three-dimensional analysis using serial section reconstruction. The number of
      classic plaques was underestimated due to a lack of precision in the usual
      evaluating procedures (two-dimensional analysis), while that of stellate deposits
      was overestimated. From these results, it was suggested that the three
      dimensional analysis by gapless serial sections was indispensable to examine and
      subclassify senile plaques.

PMID- 8301885
TI  - Effects of haloperidol on the methamphetamine sensitization: assessment by
      ambulatory activity in mice.
AB  - Haloperidol (HPD: 0.0063, 0.025, 0.1 and 0.4 mg/kg, s.c.) reduced dose
      dependently the ambulation-increasing effect of methamphetamine (MAP: 2 mg/kg,
      s.c.) in mice. The repeated administration of MAP elicited a sensitization to its
      ambulation-increasing effect, and the development of sensitization was inhibited
      when MAP was administered in combination with HPD in the repeated administration
      schedule. However, any dose of HPD could not ameliorate the established MAP
      sensitization. Whereas, the mice experienced the repeated treatment with HPD 0.4
      mg/kg showed an increase in the MAP sensitivity. The present results suggest that
      HPD, at comparatively higher doses, produces a denervation supersensitivity of
      postsynaptic dopamine receptors, and shows protective action on the development
      of MAP sensitization. However, it is also suggested that the established MAP
      sensitization is irreversible even after the treatment with HPD.

PMID- 8301886
TI  - Paradoxical GABAergic facilitation on seizure development observed from
      bicuculline-induced effects on visual cortical kindling at short interstimulus
      intervals in chronically prepared rabbits.
AB  - To investigate the influence of GABAergic function on seizure development, the
      effects of bicuculline, a GABAa receptor antagonist, on visual cortical and
      hippocampal kindling were examined in chronically prepared rabbits. Kindling
      inducing stimulations were repeated at 5-min intervals. The changes in
      afterdischarge (AD) durations were compared before and 30 min after a low (2
      mg/kg) and high dose (5 mg/kg) i.p. injection of bicuculline solution. In the
      visual cortical kindling group, the AD durations were markedly shortened after
      the low dose bicuculline injection, while bicuculline produced a prolongation of
      the AD durations in the visual cortical with the high dose injection and
      hippocampal kindling groups. The low dose bicuculline-induced inhibition of
      visual cortical kindling suggests facilitative GABAergic action on seizure
      development, while the drug-induced enhancement in the other groups reflects the
      well-known inhibitory GABAergic action.

PMID- 8301887
TI  - A study on gamma-aminobutyric acid (GABA) and its analogues by using molecular
      orbital methods: on epileptogenicity of new quinolones.
AB  - Using the molecular orbital methods, we examined molecular structure, electron
      density distribution, electrostatic potential field and receptor structure of
      gamma-aminobutyric acid (GABA), and its analogues. The following findings were
      obtained: a comparison of the biological activity and the morphology
      electrostatic potentials of GABA analogues disclosed that the active site is the
      amino group, and the biological activity correlates closely with the
      electrostatic potential structure around the amino group. The active sites were
      compared between the receptor-binding molecules and the GABA uptake inhibitory
      molecules, and the results suggested that the receptor structure differed between
      the two groups of molecules and that the GABA A receptors had two subtypes. On
      these results, the epileptogenicity of new quinolones was studied using this
      method. These results suggested that the new quinolones blockaded the GABA
      receptor-binding system and that the important active site of the new quinolones
      for GABA receptor-binding was the the piperazyl amino group. These results
      suggested that the concentration of zwitterion type of the new quinolones was
      very important clinically.

PMID- 8301888
TI  - Proceedings of the 15th Annual Meeting of the Japanese Society of Biological
      Psychiatry. Tokyo, March 17-19, 1993. Abstracts.

PMID- 8301889
TI  - [The relation between the attitude toward humor, aggression and altruism].
AB  - This study investigated the attitude towards humor and the relationship among the
      attitude, aggression and altruism. Four hundred and seven subjects answered the
      questionnaires consisting of (1) items about attitude toward humor, (2) items
      about aggression and altruism, and (3) items about humorous statements,
      frequently heared in negative situations. Factor analysis revealed that the
      attitude toward humor consists of two factors; (a) preference for aggressive
      humor and (b) preference for playful humor. The former is related to aggression
      and altruism, while the latter is related to altruism only. The items about
      humorous statements frequently heard in negative situations suggested that
      preference for aggressive humor is related to aggressive behavior, while
      preference for playful humor is related to moderation of the atmosphere.

PMID- 8301890
TI  - [The influence of face on person perception].
AB  - The purpose is to examine the influence of three factors on person perception,
      (a) the degree of facial attractiveness, (b) the order of presentation of the
      faces and the verbal information of the same stimulus person and (c) the sex of
      the perceivers. Seventy-one male undergraduates and 89 female undergraduates were
      asked to rate the personalities of the two positive and two negative stimulus
      persons of the opposite sex, who were selected by each subject in preliminary
      experiment, and asked to choose what kind of relation they would have with them.
      Positive or negative face was presented either before or after verbal
      information. The main results were as follows. (a) Generally, positive faces
      exerted greater influence than negative faces. (b) Faces presented after verbal
      information were more influential than those presented before it (recency
      effect). (c) The influence of face on male subjects was greater than that on
      female subjects.

PMID- 8301891
TI  - [The relation of ideal self to perception of self and others].
AB  - One hundred and twelve (112) junior high school students made ratings of their
      ideal and actual selves, and of other persons of same sex whom they liked or
      disliked, using uni-polar scales of 42 positive and 42 negative traits words.
      Positive and negative ideal-self rating scores correlated with those for actual
      self and others. At the same time, rating scores on important traits for each
      subject which gained the highest score in ideal-self rating differed among the
      actual self and the liked other and disliked other--the liked other was rated
      more positively than the disliked other, though self-esteem affected relative
      positiveness of actual self to liked or disliked others. However, no such
      differences were found on unimportant traits which gained lower scores in ideal
      self rating. These results seem to indicate that both positive and negative ideal
      selves provide cognitive framework for perception of self and others.

PMID- 8301892
TI  - [Differences of booklet administration from the computer form of MINI personality
      inventory].
AB  - The computer and booklet versions of MINI personality inventories, which
      contained 250 items, shortened and revised version of MMPI-1, were administered
      to 81 university students simultaneously. The results of t-test (corresponding
      sample) showed the significant difference for the raw scores of D, Pd, and Si.
      The booklet administered MINI gave slightly higher scores than the computerized
      MINI, however, the correlation analyses showed the salient coefficients between
      both versions. The analyses of response frequencies for each item showed no
      significant difference. Results suggested that the slight change in norms was
      needed for booklet version, because the MINI was standardized by computer form.

PMID- 8301893
TI  - [Analysis of clinical cases adopting three-mode factor analysis].
AB  - The purpose of the present study was to examine sequentially the evaluations of
      the self and others in psychotherapy using the Rating Grid Method, one of the
      Repertory Grid Techniques. A construct system of Subject A was composed of
      "pleasant-painful", "steady-hopeless", "stable-anxious", "comfortable-irritable",
      "feeling of freedom-feeling of pressure", "specific-vague", "strong-week", and
      "refreshing-gloomy". That of Subject B consisted of "fearful-not fearful",
      "composed-restless", "pleasant-painful", "dignified-undignified", "eager-lazy",
      "realistic-mysterious", "perfectionism-slipshod", and "decisive-irresolute". The
      evaluations of the two subjects in the Rating Grid Method were analyzed using
      three-mode factor analysis. These results were then compared with diagnoses
      obtained through psychotherapy.

PMID- 8301894
TI  - [Influence of articulatory suppression and memory updating on phonological
      similarity effect].
AB  - Two experiments were conducted to investigate whether articulatory suppression
      and memory updating affect phonological similarity effect. In the first
      experiment, 24 subjects were tested for immediate serial recall of visually
      presented letter sequences in which letters were either phonologically similar or
      dissimilar within each sequence. Each block of the letter sequences was to be
      remembered under silent reading or articulatory suppression conditions. The
      results showed the advantage of the dissimilar condition over the similar
      condition in the silent reading condition. On the other hand, this phonological
      similarity effect was not shown in the articulatory suppression condition. Twelve
      subjects participated in the second experiment on the effect of memory updating.
      Memory updating reduced the recall performance, but it did not affect the
      phonological similarity effect. These results were interpreted in terms of the
      working memory model.

PMID- 8301895
TI  - [Trend in person-situation controversy about personality research].
AB  - The purpose is to review the trend in "person-situation controversy", and to
      comment on recent literature and their implications. "Person-situation
      controversy" is related to whether people do or do not have consistent
      personality traits. Although the topic is not at all new, it aroused a great deal
      of interest since the publication of Mischel's (1968) "personality and
      assessment". Here, we began with Mischel's criticism against the trait approach,
      then, we discussed two opposite viewpoints of situationism and interactionism.
      Situationism is the idea that situational variables influence more on the
      behavior of people than personality traits, while interactionism is the idea that
      personality traits and situations interact with each other to influence behavior.
      Furthermore, this article focussed on three conceptual issues, such as
      consistency, prediction, and meaning of traits. Finally, the reconsideration and
      evaluation of the two viewpoints were presented from a viewpoint of personality
      psychology.

PMID- 8301896
TI  - [Usefulness of mixed venous oxygen saturation as a monitor of hemodynamic state
      during pulmonary resection].
AB  - We studied the relation between SVO2 and other hemodynamic parameter during lung
      resection in 28 patients. SVO2, SaO2, CI, Hb and VO2 were measured using a
      fiberoptic pulmonary artery catheter. SaO2 decreased significantly after collapse
      of a nondependent lung because of shunt effect, whereas SVO2 remained stable. VO2
      and CI increased remarkably and SVO2 decreased gradually after restoration of two
      lung ventilation suggesting imbalance of auto-regulatory mechanism. SVO2 remained
      significantly low after extubation in patients whose blood loss of more than
      1,000 ml was replaced by stored blood transfusion. We think that the constant
      number 1.38 in Fick equation should be reset below 1.38 according to the volume
      of transfused blood, if blood loss was replaced by stored blood.

PMID- 8301898
TI  - [A case of early hilar lung cancer combined with intralobar pulmonary
      sequestration, both of which were treated by limited lung resection].
AB  - A 59-year-old man complained of fever due to infection in the intralobar
      pulmonary sequestration. On bronchoscopic examination, squamous cell carcinoma
      was found out at orifice of the left upper division bronchus. His pre-operative
      pulmonary function test showed low pulmonary reserve because of myelopathy. He
      underwent left S1 + 2 + S3 sleeve segmentectomy and S9 + 10 segmentectomy for
      intralobar pulmonary sequestration. He is well without any evidence of recurrence
      10 months after surgery.

PMID- 8301897
TI  - [Emergency coronary artery bypass grafting with warm blood cardioplegia for a
      patient with acute myocardial infarction and severe left ventricular
      dysfunction].
AB  - Emergency coronary artery bypass grafting was performed in a 61 year old man who
      developed acute severe cardiac and respiratory dysfunction after myocardial
      infarction. At operation cardiac arrest was obtained by warm blood cardioplegia
      in antegrade intermittent fashion. The left anterior descending artery, diagonal
      branch, and right coronary artery were revascularized by saphenous vein (SVG).
      After declamping the aorta, spontaneous heart beating was obtained and
      postoperative course was uneventful. Postoperative examination showed patent all
      SVGs and improved cardiac function. Although the delivery of the warm blood
      cardioplegia was controversial, our recent study revealed that the intermittent
      antegrade delivery of warm blood cardioplegia showed no ischemic changes of the
      heart during the procedure.

PMID- 8301899
TI  - [A case underwent separate operation for AAE, AR and TAA using elephant trunk
      method].
AB  - A 20-year-old man with Marfan syndrome was recommended emergency operation for
      impending rupture of TAA. Because he was in the state of acute heart failure due
      to coexisting AAE and AR, so the simultaneous operations for AAE, AR and TAA were
      needed. He underwent Bentall, arch replacement and elephant trunk operation
      utilizing separate extracorporeal circulation and circulatory arrest. Chest CT,
      taken after 5 months postoperatively, revealed only a small amount of thrombus in
      TAA. Anticoagulation therapy stood in the way of aneurysmal thrombo-exclusion.
      The second operation, grafting of descending thoracic aorta, was performed 6
      months later and elephant trunk made the second operation easier. Now 12 months
      passed after the second operation, he is in good health.

PMID- 8301900
TI  - [Combined operations of coronary artery bypass grafting using the right gastro
      epiploic artery and other abdominal operation].
AB  - We carried out combined operation of coronary artery bypass grafting using the
      right gastro-epiploic artery (GEA) and other abdominal operation in four
      patients. The abdominal operation were one total gastrectomy for double early
      gastric cancer, one bypass with Y-shaped graft for arteriosclerosis obliterans in
      iliac region and two peritoneal dialysis for chronic renal failure. There were no
      early death. The postoperative course was uneventful without any mediastinitis or
      other infectious events. Doing careful maneuver, we can use the GEA for grafts in
      such cases.

PMID- 8301901
TI  - [Successful patch angioplasty for the right coronary artery dissection following
      selective coronary perfusion].
AB  - A case of successful patch angioplasty for the right coronary artery (RCA)
      orifice dissection following selective coronary perfusion is reported. A 56-year
      old woman who had mitral restenosis, aortic stenosis, and atrial fibrillation
      with bradycardia-tachycardia syndrome was referred to our hospital for operation.
      The operation, which contained aortic valve replacement and mitral
      commissurotomy, was performed with hypothermic cardiopulmonary bypass and
      crystalloid cardioplegic arrest. The ascending aorta was opened, and selective
      coronary perfusion was performed. The right coronary cannula was difficult to
      insert and dislodged several times. At the second infusion of the cardioplegic
      solution, the right coronary orifice and ascending aortic wall was dissected. The
      dissection extended to the proximal RCA. The aortotomy was extended into the RCA
      beyond its orifice. The Xenomedica pericardial patch was used to enlarge the
      diameter of the RCA with closing the dissected cavity. Then the patch was brought
      onto the side of the aorta and the aortotomy was closed in the usual manner. Post
      operative coronary angiography revealed widely patent RCA orifice and good
      runoff. Two years after operation the patient is free of angina with unlimited
      physical activity.

PMID- 8301902
TI  - [Late cardiac tamponade after open heart surgery].
AB  - 59 cases of late cardiac tamponade following open heart surgery were studied. The
      incidence was 2.1%. Postoperative prolonged heart failure, anticoagulants, and
      blood in the pericardium left undrained may play a role in its pathogenesis.
      Echocardiography was the sure method of diagnosis. Insertion of a drainage tube
      into the pericardium through the subxiphoid approach was effective with minimal
      invasion and a treatment of choice.

PMID- 8301903
TI  - [Successful treatment by Konno's operation for congenital aortic stenosis
      associated with hypoplastic valve ring].
AB  - A 47-year-old woman with congenital aortic stenosis associated with hypoplastic
      aortic valve ring underwent aortic valve replacement by Konno method. We have to
      be careful preventing residual VSD because the left ventricular muscle was weak
      in the aged with congenital aortic stenosis. In early postoperative period, we
      also have to do a careful treatment in case by Konno's operation, particularly in
      the patient of advanced age. However, she made a satisfactory recovery with
      adequate size of aortic valve replacement.

PMID- 8301904
TI  - [A case of unroofed coronary sinus with persistent left superior vena cava].
AB  - A 44-year-old female with left to right shunt and persistent left superior vena
      cava (PLSVC) suspected of unroofed coronary sinus defect with patent right SVC
      and innominate vein was treated surgically. PLSVC was ligated and coronary sinus
      ostium was closed with a EPTFE patch. Roof defect of coronary sinus was left open
      and allowed the coronary venous blood to drain into the left atrium. Patient
      recovered well and post-operative cardiac catheterization revealed no significant
      right to left shunt nor desaturation of arterial blood. In the correction of
      unroofed coronary sinus defect and PLSVC and no other intra-cardiac defect,
      ligation of PLSVC and closure of coronary sinus ostium was simple and effective,
      although it was not anatomically corrected.

PMID- 8301905
TI  - [A case report of cervical aortic arch complicated with succiform aneurysm].
AB  - Left-sided cervical aortic arch in 30-year-old woman complicated with succiform
      arch aneurysm was reported. Aneurysm was successfully removed and arch was
      reconstructed by end to end anastomosis. Histological examination of aneurysm
      revealed atherosclerotic change and calcification.

PMID- 8301906
TI  - [Symbas's operation in a case of congenital fistula of the right coronary artery
      to left ventricle].
AB  - Congenital fistula between a coronary artery and the left cardiac ventricle are
      extremely rare. Since Blakeway (1918) first described this type of anomaly, only
      72 cases have been reported up to the present, within our knowledge. A surgical
      correction of congenital fistula of the right coronary artery to left ventricle
      in a 36 year-old woman who suffered from easy fatigability is reported. This
      lesion was deduced after echocardiography identified a dilated right coronary
      artery and fluttering of the posterior cusp of the mitral valve throughout the
      diastole, the diagnosis was confirmed by retrograde aortography and coronary
      angiography. The fistula was closed by Symbas's operation under cardiopulmonary
      bypass with cardiac arrest and mild hypothermia. Postoperative recovery was
      uneventful. Coronary angiography one month after the operation revealed that the
      right coronary artery was still dilated with thrombus; there were no signs of
      myocardial ischemia or infarction. This diagnosis and successful treatment were
      based on careful study of the documentation of the 72 previously reported cases.

PMID- 8301907
TI  - [A case of malignant localized chest wall mesothelioma accompanying with
      abdominal aortic aneurysm].
AB  - The patient was a 78-year-old man with a history of large painful left lower
      lateral chest wall tumor that was fist sized, while he had large abdominal aortic
      aneurysm. Because of high age, two staged operation was done. Initially chest
      wall tumor was resected. The defect was 11 x 11 cm in sized. The reconstruction
      of the defect was made with Marlex mesh. The microscopical findings was biphasic
      malignant mesothelioma. Fourty one days later abdominal aortic aneurysm was
      excised and the aorta was reconstructed using a Y shaped artificial graft. Post
      operative course was uneventful.

PMID- 8301908
TI  - [A case of foreign body granuloma].
AB  - A 45-year-old man referred to our hospital complaining of dry cough. Chest X-ray
      and CT scan film indicated tumor shadow in the right anterior mediastinum.
      Although preoperative diagnosis was teratoma, the specimen extirpated by
      thoracotomy revealed macroscopically and microscopically foreign body granuloma
      originated from gauzes. He had undergone segmentectomy of right upper lobe for
      tuberculosis 28 years ago, so the gauzes were thought to be left in right
      thoracic cavity at the operation. The foreign body granuloma originated from
      gauzes are iatrogenic and few cases were reported previously, however, whirl like
      pattern demonstrated by MRI is retrospectively considered to be an important
      diagnostic finding in this case.

PMID- 8301909
TI  - [A surgical case of achalasia with empyema].
AB  - A 57-year-old man who had been complicated with achalasia for thirty years was
      admitted because of back pain and low grade fever. Chest X-p and Chest CT showed
      consolidation in the left lower lung field. His respiratory condition was
      diagnosed as lung abscess preoperatively. After systemic chemotherapy, surgical
      management was done for both achalasia and this inflammatory respiratory disease.
      In the operation by left thoracotomy, it was revealed that this case had empyema,
      not lung abscess. Thus decortication of left lung and esophagomyotomy were
      performed simultaneously. In the treatment of achalasia, respiratory
      complications due to aspiration may appear. In addition, it is sometimes
      difficult to distinguish empyema from lung abscess preoperatively. Therefore much
      care should be taken during operation in order to treat these respiratory
      diseases.

PMID- 8301910
TI  - [Experience with a operated cervico-mediastinal neuroblastoma in infant].
AB  - Cervical neuroblastoma is relatively rare and shows very good prognosis. We
      reported a case of surgically resected cervico-mediastinal neuroblastoma. A 7
      month-old boy was pointed out to have Horner syndrome (right ptosis and
      anhidrosis) and an abnormal shadow at right cervico-mediastinum on chest X-ray
      film during his stay in another hospital because of acute bronchitis. On
      examination after admission in our hospital, 3 x 4 cm size mass was palpated at
      the right neck and urine VMA and HVA level were elevated. The close examination
      demonstrated no sign of tumor in any other organ and tissue, which suggested that
      the tumor was cervical origin. 9 x 5, 5 x 3 cm tumor was almost removed and
      patient received chemotherapy. He is now free from disease at 1 year after
      operation.

PMID- 8301911
TI  - [A case of mediastinal cystic lymphangioma: with special reference to
      ultrasonographic findings].
AB  - We reported a rare case of mediastinal cystic lymphangioma, which happened to be
      discovered on chest X-ray. CT density level of the mediastinal tumor was 20 HU
      and the tumor was homogeneous cystic lesion. Multilocularity of the cyst and the
      relationship to the adjacent inferior vena cava were clarified by pre-operative
      transesophageal and intraoperative ultrasonographic examination, and the tumor
      was successfully excised without mishap.

PMID- 8301912
TI  - [A case of intrathoracic meningocele associated with neurofibromatosis].
AB  - A rare case of intrathoracic meningocele associated with neurofibromatosis was
      reported. A 47-year-old female was admitted to our institute because of an
      abnormal shadow on chest X-ray. The chest X-ray film showed homogenous opacity
      with a well defined margin in the right apex. Chest CT showed an enlarged
      intervertebral foramen and defect of the vertebral arch around the tumor. There
      was no scoliosis. Though preoperative diagnosis was dumbbell type neurinoma, the
      tumor was found to be a protrusion of dura mater with spinal fluid out of the
      spinal canal, covered by thickening tumorous tissue. Part of the wall was excised
      and the residual opening was carefully repaired and wrapped by the pedicled
      parietal pleura. Retrospectively, MRI showed characteristic findings of
      intrathoracic meningocele. The tumorous part of it was diagnosed as neurofibroma
      on histological examination.

PMID- 8301913
TI  - [Use of inferior epigastric artery for coronary artery bypass grafting].
AB  - Between 3/91 and 3/93 twenty-nine patients (pts.) with a mean age of 55 years (30
      68) underwent CABG (including 3 reoperation) using inferior epigastric artery
      (IEA) in addition to internal thoracic artery and saphenous vein graft. IEAs were
      harvested as pedicles with a mean length of 12.2 cm (7.5-17). Overall distal
      anastomoses were performed 3.2 per patients. And a mean of 2.3 anastomoses were
      completed as an arterial graft. IEA grafts were applied to left anterior
      descending artery in 10, diagonal branch in 15, in marginal branches in 2 and
      right coronary artery in 2. Mean cardiopulmonary bypass time amounted to 103
      minutes and operation procedures were completed in 258 minutes (mean). Aortic
      cross clamp time of 48 minutes were required. One patient was died of cerebral
      accident 23 days postoperatively. Except for two abdominal wall infection no
      wound healing problems occurred. One reexploration for bleeding were necessary.
      Postoperative angiography revealed patent IEA grafts in 12 of 13 patients (92%).
      We concluded that the application of IEAs for CABG is available as a third
      arterial graft and with respect to intraoperative management and perioperative
      complications use of IEA combined with ITAs appears suited or superior to the use
      of the right gastroepiploic artery.

PMID- 8301914
TI  - [Surgical treatment of atherosclerotic vascular diseases associated with coronary
      artery disease].
AB  - Selective coronary angiography to determine the incidence of coronary artery
      disease (CAD) has been performed in the 38 patients with atherosclerotic vascular
      disease. significant CAD was demonstrated in 17 of 23 (73.8%) patients with
      angina pectoris or previous myocardial infarction, in 4/15 (26.7%) patients who
      had no clinical evidence of CAD. There were no early and late postoperative death
      in the 9 patients who underwent simultaneous coronary artery bypass graft and
      vascular operations or percutaneous coronary angioplasty, on the other hand,
      there were one early and four late death in the 11 patients who underwent only
      vascular procedure.

PMID- 8301915
TI  - [Results of initial bacteriology of pulmonary tuberculosis among male NTT
      employees in the Tokyo area--annual transition and influence of fiberoptic
      bronchoscopy].
AB  - A study was made on the annual changes in the positive rate for acid-fast bacilli
      (AFB) at the initial bacteriological examination of newly detected pulmonary
      tuberculosis among male NTT (Nippon Telegraph and Telephone Corporation)
      employees in the Tokyo area during a period of 32 years from 1960 through 1991.
      The influence on the changes of recent introduction of fiberoptic bronchoscopy
      for obtaining the specimen was also analyzed, and the following results were
      obtained. 1. Results obtained by the conventional bacteriological method using
      expectorated sputum or aspirated gastric juice as the specimens. (1) The annual
      incidence of bacteriologically positive (smear and/or culture positive) cases
      constantly decreased and reached the lowest in 1981, then ceased to decline and
      remained at the level of 1981. (2) The annual ratio of AFB positive by smear and
      the ratio of smear and/or culture positive cases to the newly detected cases of
      pulmonary tuberculosis were constant during the entire observation period. (3)
      The ratio of AFB positive by smear to the newly detected cases annually increased
      but did not increase when the observation period was limited to within 1976 to
      1991. 2. Results obtained by fiberoptic bronchoscopy in combination with
      conventional bacteriological methods. (1) Both the annual incidence of smear
      and/or culture positive cases and the ratio of these cases to the newly detected
      cases of pulmonary tuberculosis showed a tendency to increase in both the 80's
      and 90's.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301916
TI  - [Investigation of tracheo-bronchial tuberculosis cases].
AB  - A total of 1397 patients were admitted to our hospital between 1986 and 1992. Of
      those patients, 68 were diagnosed as having tracheo-bronchial tuberculosis, when
      examined using a bronchofiberscope. We investigated the cases of 50 patients who
      were examined during the early stages of the diagnosed them as having pulmonary
      tuberculosis. The number of women in the group was larger than men, and young
      patients made up 30% of the group. Upon admission to the hospital, all of the
      patient's sputum examinations were tested positive, but their chest
      roentgenograms did not show a progressive stage. After treatment, patient
      roentgenograms showed improvement, however there was no improvement in tracheo or
      bronchial conditions. It was therefore believed that therapy was impeded by
      tracheobronchial tuberculosis, but only one patient was treated surgically. It
      was deemed that the delay of patients seeking treatment was not long, however,
      the delay for doctors in beginning therapy was very long. Many of the patients
      with tracheo-bronchial tuberculosis complained of coughing and sputum, therefore
      diagnosis and therapy should be performed as soon as possible.

PMID- 8301917
TI  - [Therapeutic efficacy of a benzoxazinorifamycin, KRM-1648, combined with a
      immunopotentiator, LC9018, in Mycobacterium intracellulare infection induced in
      beige mice].
AB  - A study was performed on the therapeutic efficacy of KRM-1648 combined with
      LC9018 in beige mice infected with Mycobacterium intracellulare. Each mouse was
      intravenously infected with 3.9 x 10(6) CFU, and then given 0.2 mg of KRM-1648
      emulsified in 2.5% gum arabic-0.2% Tween 80 by gavage once a day, six times per
      week, beginning 24 h after infection for up to eight weeks. A sc injection of 0.1
      mg LC9018 in saline was given once or twice per week, beginning two weeks before
      infection to the end of experiment. An evaluation of the therapeutic efficacy of
      these drugs against the infection was performed on the basis of incidence and
      degree of gross lung lesions and bacterial loads in the lungs and spleen. Lung
      lesions were not observed in all experimental groups at four weeks after
      infection. However, at eight weeks after infection, although lung lesions were
      observed in all experimental groups, the degree of lesions was much milder in
      those mice receiving KRM-1648 than in the control mice. The degree of lesions in
      the mice receiving LC9018 was much the same as that in the control mice.
      Moreover, the degree of lung lesions in mice treated with KRM-1648 alone. The
      CFUs of organisms in the lungs and spleen of the mice treated with KRM-1648 were
      considerably lower than those of the control mice (P < 0.05), but the CFUs in the
      mice treated with KRM-1648 and LC9018 were nearly the same as those mice treated
      with KRM-1648.

PMID- 8301918
TI  - [A case of local reactivation of tuberculous peritonitis with suspected gastric
      submucosal tumors after laparotomy].
AB  - After complaining of right hypochondrial pain, a 36-year old man was diagnosed as
      having a gastric submucosal tumor at a nearby hospital and admitted to Chiba
      Cancer Center Hospital. On admission, a hard and immobile mass was palpable on
      the right upper quadrant. Laboratory findings were within normal limits. A chest
      X-ray revealed bilateral pleural adhesions and streaking shadows in the bilateral
      lung area. These findings were assumed to be due to a prior tuberculous
      infection. Upper gastrointestinal series and endoscopic examination showed a
      protruding lesion on the stomach body. An abdominal CT showed another lesion
      adjacent to the stomach antrum. A resection was carried out under the presumptive
      diagnosis of multiple gastric submucosal tumors. Exploration of the abdomen
      revealed widespread fibrous adhesion suspected to be due to prior old tuberculous
      peritonitis. Two tumors were located here. One was adjacent to the stomach body,
      and the other was adjacent to the liver and abdominal wall. Pathologically, both
      were caseated necrotizing granulomas composed of mature epithelioid cells and
      Langhans giant cells. A close examination revealed that one originated from the
      serosa of the stomach and the other from the peritoneum. Both were believed to be
      relatively new lesions. Pus obtained from the tumors tested positive for acid
      fast bacilli. A post-operative tuberculin skin test was given and checked highly
      positive. From these findings, this case was diagnosed as local reactivation of
      old tuberculous peritonitis. After antituberculous chemotherapy at our hospital,
      the patient was discharged and sent home without any symptoms. The reason for the
      local reactivation was unknown.

PMID- 8301919
TI  - [An autopsy case of atypical mycobacteriosis accompanied with chest wall
      deformity].
AB  - An autopsy case of 63-year old male of atypical mycobacteriosis with severe
      scoliosis was reported. He was diagnosed as atypical mycobacteriosis in 1981 and
      controlled by antimycobacterial treatment. But since 1989, dyspnea and sputum
      have been increasing, new abnormal shadow in company with progression of
      curvature of the scoliosis was revealed on the chest roentgenogram. In spite of
      various treatments for mycobacteriosis, he died of respiratory failure. The
      aggravation of this mycobacteriosis brought on advancement of malnutrition and
      impairment of cell mediated immunity. Findings of autopsy showed the remarkable
      chest wall deformity and tuberculous change of the lung parenchyma. In this case,
      chest deformity was thought as the major risk factor of onset of mycobacterial
      mycobacteriosis.

PMID- 8301920
TI  - [Commemorative lecture of receiving Imamura Memorial Prize. Characterization of
      immunosuppressive macrophages induced in mice infected with Mycobacterium
      intracellulare].
AB  - Functional changes in T lymphocytes and macrophages (M phi s) in host mice during
      the course of Mycobacterium intracellulare infection were studied. In both
      strains of mice, BALB/c or C57BL/6 (susceptible to M. avium complex) and CBA/JN
      or C3H/He (resistant to M. avium complex), the smooth, opaque and dome-shaped
      colonial (SmD) variants of M. intracellulare were easily eliminated from the
      sites after week 2 of infection. In contrast, the smooth, transparent and
      irregularly shaped colonial (SmT) variants showed steady growth in the former
      strains of mice and persisted for long time even in the latter strains of mice.
      No difference was found between persistence of the organisms in euthymic (+/+)
      and athymic (nu/nu) BALB/c mice during the first 4 weeks after infection.
      Thereafter, more rapid growth was seen in the spleens and lungs of nu/nu mice.
      Thus, matured T cells may be important for the prevention of the progression of
      M. intracellulare infection to the terminal state. Next, the profiles of
      generation and characteristics of splenic M phi s which suppress the Con A
      mitogenic response of splenic T cells in host CBA/JN or BALB/c mice during the
      course of M. intracellulare infection were investigated. In M. intracellulare-
      infected mice, reduction in some cellular functions of host splenic T cells, such
      as the Con A mitogenic response and mixed leucocyte reaction, were seen around 2
      weeks after infection, and this was accompanied by appearance of
      immunosuppressive M phi s in spleen cells (SPCs).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8301921
TI  - A molecular approach to inherited kidney disorders.

PMID- 8301922
TI  - Role of endothelin and prostaglandins in radiocontrast-induced renal artery
      constriction.
AB  - Infusion of radiocontrast agents in vivo results in renal artery constriction and
      subsequent renal hypoperfusion. To examine the role of endothelin and of
      prostaglandins in radiocontrast-mediated renal vasoconstriction, rats were
      treated with an endothelin receptor antagonist, CP170687, and with indomethacin.
      The dose of CP170687 utilized was sufficient to reverse endothelin1-mediated
      constriction of isolated aortic rings and of renal blood flow in intact rats. In
      normal rats there was a transient drop in renal blood flow to 80% of baseline
      following sodium iothalamate injection, an effect which was not prevented by
      CP170687. In rats first given indomethacin, the drop in renal blood flow was more
      pronounced (to 63% of baseline) and was sustained. In this instance, CP170687
      fully reversed the sustained decrease of renal perfusion. CP170687 also
      diminished the rise in systemic blood pressure seen following iothalamate
      injection. In the absence of indomethacin, iothalamate increased urinary
      prostaglandin E2 to a maximum of sevenfold above baseline values. In summary,
      injection of radiocontrast results in an immediate decrease in renal blood flow
      that is counteracted by an increase in renal prostaglandin formation. When
      prostaglandin synthesis is inhibited, prolonged endothelin-mediated renal
      vasoconstriction is observed that is reversed by an endothelin receptor
      antagonist.

PMID- 8301923
TI  - Effect of metabolic acidosis on the expression of insulin-like growth factor and
      growth hormone receptor.
AB  - To further our understanding of the growth failure in metabolic acidosis, we
      examined the insulin-like growth factor (IGF-I and IGF-II), the IGF binding
      protein-3 (IGFBP-3), and the hepatic IGF mRNA and growth hormone receptor mRNA in
      control, pair-fed and acidotic rats. The rats in the last group were made
      acidotic by using ammonium chloride (1.5%) as their sole fluid intake for eight
      days. Metabolic acidosis was confirmed by a blood pH of 7.11 +/- 0.10 (mean +/-
      SD). The mean starting weights for all rats were 167.1 +/- 3.4 grams. Growth
      impairment was observed in the acidotic rats after one week of ammonium chloride
      intake. The body weights of the acidotic rats compared to those of the control
      rats were 155.5 +/- 18.9 g versus 222.8 +/- 9.7 g, P < 0.001; the pair-fed rats
      weighed 156.8 +/- 19.6 grams. All rats were bled and sacrificed on day 8. Sera
      and tissue were analyzed with the following results: compared to the ad libitum
      controls, the same IGF-I concentrations were significantly decreased in the
      acidotic animals (P < 0.02) as well as pair-fed controls (P < 0.005). The serum
      IGF-II and IGF-binding protein-3 concentrations were unchanged by acidosis or
      food restriction. The hepatic IGF-I mRNA was significantly reduced by acidosis (P
      < 0.01) and pair-feeding (P < 0.01). Compared to control, the mean hepatic IGF
      mRNA in acidosis was significantly lower (P < 0.01). However, there was no
      significant difference between the acidotic and the pair-fed groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301924
TI  - Evidence suggesting that iron and calcium are interrelated in oxidant-induced DNA
      damage.
AB  - The effect of iron chelators and agents that buffer cytosolic-free calcium
      ([Ca2+]i) on hydrogen peroxide-induced DNA strand breaks in LLC-PK1 cells has not
      been previously examined. In addition, the interrelationship between iron and
      calcium in the pathogenesis of DNA damage has not been studied in any model of
      tissue injury. Exposure of LLC-PK1 cells to 1 mM hydrogen peroxide resulted in
      marked DNA damage, as measured by the alkaline unwinding assay (residual intact
      double stranded DNA at 10 min, control: 88 +/- 1%; hydrogen peroxide-treated
      cells: 17 +/- 3%, N = 8). The iron chelators, 1,10-phenanthroline and
      deferoxamine, and agents which buffer [Ca2+]i, BAPTA and quin-2, provided highly
      significant protection against hydrogen peroxide-induced DNA strand breaks. We
      then examined the effect of iron chelators on hydrogen peroxide-induced rise in
      [Ca2+]i in LLC-PK1 cells. Both 1,10-phenanthroline and deferoxamine prevented the
      marked and sustained rise in [Ca2+]i induced by exposure of LLC-PK1 cells to 1 mM
      hydrogen peroxide ([Ca2+]i at 15 min, control 100 +/- 3 nM; hydrogen peroxide 195
      +/- 14 nM; 1,10-phenanthroline + hydrogen peroxide 100 +/- 4 nM; deferoxamine +
      hydrogen peroxide 106 +/- 4 nM; N = 4). We excluded the possibility that the iron
      chelators were directly chelating calcium by performing experiments using a cell
      free system. We also confirmed that BAPTA and quin-2, in concentrations used in
      our study, chelate calcium but not iron or copper.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8301925
TI  - Changes in pH affect Cl- removal and AVP action in collecting tubules.
AB  - We examined what mechanisms are involved in the alteration by chloride (Cl-)
      removal of arginine vasopressin (AVP)-induced cellular cAMP production, and
      cellular free calcium ([Ca2+]i) mobilization in rat renal papillary collecting
      tubule cells in culture, using two buffer systems: bicarbonate and non
      bicarbonate buffers. The first study was performed in the bicarbonate
      supplemented buffer. Removal of Cl-, which was replaced by methylsulfonate or
      gluconate, increased cellular pH (pHi) from 7.19 to 7.26. AVP increased cellular
      cAMP production in a dose-dependent manner; 1 x 10(-9) and 1 x 10(-7) M AVP
      induced increases in cellular cAMP production were significantly enhanced by the
      Cl- removal. Also, 1 x 10(-7) M AVP-mobilized [Ca2+]i was augmented by the Cl-
      removal (181.3 vs. 224.5 nM, P < 0.05). The second study was carried out with the
      Krebs-Ringer buffered saline (KRB). Removal of Cl- lowered pHi from 7.20 to 7.09.
      AVP-induced increases in cellular cAMP production were significantly reduced in
      the Cl(-)-free KRB compared to those in the KRB. The reduction was obtained with
      KRB containing less than 25 mM Cl-. Similar results were obtained with 2 x 10(-8)
      M forskolin, a diterpene activator of adenylate cyclase. 1 x 10(-7) M AVP
      mobilized [Ca2+]i was also diminished by the Cl(-)-free KRB. These results
      indicate that Cl- depletion affects the cellular response to AVP mediated via the
      changes in pHi in renal papillary collecting tubule cells.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8301926
TI  - Distribution and relevance of insulin-like growth factor-I receptor in
      metanephric development.
AB  - During embryogenesis, various ligand-receptor interactions take place to modulate
      the development and growth of various mammalian organs. During these
      interactions, a critical concentration of a given receptor is needed to elicit a
      ligand-induced biologic response at a defined gestational stage of the fetus. In
      this study, the distribution and the relevance of insulin-like growth factor-I
      receptor (IGF-IR) in metanephric development was investigated. Kidneys were
      harvested from mouse embryos at days 13 to 19 of fetal gestation, and maintained
      in a metanephric culture system. Immunofluorescence studies, using anti-IGF-IR,
      revealed a high expression of IGF-IR at day 13, which declined during the later
      stages of gestation through neonatal life. To study the relevance of IGF-IR
      expression in metanephric development, antisense-oligodeoxynucleotide (ODN)
      experiments were carried out. Antisense-ODN 43 mer probes were synthesized
      utilizing rat IGF-IR cDNA selected nucleotide sequences which are highly
      conserved in other mammalian species. Southern blot analyses of various
      restriction fragments of the rat and mice genomic DNA yielded similar bands when
      hybridized with the antisense-ODN or rat IGF-IR cDNA, suggesting a high degree of
      homology in the region of the gene selected for the synthesis of antisense-ODN.
      Also, the antisense-ODN hybridized with the appropriate murine fetal kidney mRNA
      species, as ascertained by S1 nuclease protection assay. Inclusion of antisense
      ODN in the culture medium resulted in an inhibition of the growth of the kidney,
      reduction in the population of the nephrons and disorganization of the ureteric
      bud branches.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301927
TI  - Intermittent versus continuous administration of 1,25-dihydroxyvitamin D3 in
      experimental renal hyperparathyroidism.
AB  - Conflicting results have been reported regarding the efficacy of intermittent
      versus continuous administration of 1,25(OH)2D3 in renal secondary
      hyperparathyroidism. To address this issue we examined sham-operated control rats
      and hyperparathyroid rats with subtotal (5/6) nephrectomy (Nx). The Nx animals
      (20 to 22 animals per group) were subjected to three treatment protocols: (i)
      solvent treatment (Nx-solvent); (ii) two i.p. injections of 35 pmol 1,25(OH)2D3
      on days 0 and 4 (Nx-bolus); and (iii) continuous infusion of 70 pmol 1,25(OH)2D3
      over six days via osmotic minipump (Nx-infusion). All measurements were performed
      six days after start of treatment. As compared to sham-operated controls, the pre
      pro-PTH/beta-actin mRNA ratio was 2.04-fold higher in Nx-solvent. Both modes of
      administration of 1,25(OH)2D3 resulted in inhibition of PTH mRNA concentrations
      relative to Nx-solvent. The pre-pro-PTH/beta-actin mRNA ratio was, however,
      significantly lower (P < 0.05) in Nx-bolus than in Nx-infusion (Nx-bolus 1.26
      higher than sham-operated controls; Nx-infusion 1.65 higher than sham-operated
      controls). Aminoterminal PTH (N-PTH) serum concentrations were higher in Nx
      solvent (52 +/- 4 pg/ml) than in sham-operated controls (32 +/- 3 pg/ml, P <
      0.01). N-PTH concentrations in Nx-bolus (38 +/- 4 pg/ml) were significantly lower
      than in Nx-solvent (P < 0.01) and in Nx-infusion (46 +/- 4 pg/ml, P < 0.05).
      Parathyroid gland weight (microgram/g body wt) was higher in Nx-solvent (1.30 +/-
      0.08 pg/ml) than in sham-operated controls (0.79 +/- 0.04 pg/ml, P <
      0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301928
TI  - Captopril inhibits the 72 kDa and 92 kDa matrix metalloproteinases.
AB  - Gelatinases are metalloproteinases in the kidney which can cleave type IV
      collagen as well as gelatin. We partially purified the 72 kDa and 92 kDa
      gelatinases. The gelatinolytic activity was measured by zymography and a
      quantitative biotin-avidin assay. By zymography, captopril in concentrations of
      20 mM and 40 mM added to the incubation buffer reduced the gelatinolytic activity
      in a dose-dependent manner. The addition of zinc in a concentration of 50 to 100
      microM reversed most of the inhibitory effect of captopril. By the biotin-avidin
      assay, captopril in a concentration of 30 to 50 nM reduced half of either the 72
      kDa or 92 kDa gelatinolytic activity. Zinc in a concentration of 50 microM
      completely reversed the inhibitory effect of 1 microM captopril on both
      gelatinases. Lisinopril, a non-sulfhydryl ACE inhibitor, similarly inhibited the
      gelatinases, but a 100-fold higher concentration of the drug was needed. These
      findings suggest that captopril reversibly inhibits the 72 kDa and 92 kDa
      metalloproteinases by interacting with the zinc ion at their active sites. This
      inhibitory effect is observed with captopril levels comparable to the
      concentrations needed to inhibit the angiotensin converting enzyme in vivo and
      may at least partially explain some of the renoprotective effects seen with this
      drug.

PMID- 8301929
TI  - Expression of endothelin-3 mRNA along rat nephron segments using polymerase chain
      reaction.
AB  - Endothelin (ET) is now known to be a family of three distinct peptides. Although
      many reports have studied the renal action of ET-1, comparatively little is known
      concerning ET-3. We previously reported that ET-1 mRNA is expressed in glomerulus
      (Glm) and inner medullary collecting duct (IMCD). In this study,
      microlocalization of mRNA coding ET-3 was carried out in the rat kidney using a
      reverse transcription and polymerase chain reaction (RT-PCR) assay of individual
      microdissected renal tubule segments along the nephron, Glm, vasa recta bundle,
      and arcuate arteries. Large signals for ET-3 PCR product were detected in
      proximal convoluted and straight tubules, cortical collecting duct, and outer
      medullary collecting duct. Glm, IMCD, and vasa recta bundle also expressed
      relatively large amounts of ET-3 mRNA. Small signals were found in medullary
      thick ascending limb, inner medullary thin limb, and arcuate artery. We detected
      ET-3 protein in tubule suspensions from cortex, outer medulla, and inner medulla
      of rat kidney. Furthermore, incubation with TGF-beta did not change ET-3 PCR
      signal, whereas ET-1 PCR signal was increased significantly by exposure to TGF
      beta in Glm and IMCD. Thus, ET-3 and ET-1 are distributed differently along the
      nephron and are regulated in different manners. This suggests that ET-3 and ET-1
      may affect kidney functions in different ways.

PMID- 8301930
TI  - Recombinant human growth hormone exacerbates chronic puromycin aminonucleoside
      nephropathy in rats.
AB  - Growth failure is a cardinal feature of chronic renal failure in children.
      Administration of recombinant human growth hormone (rhGH) ameliorates this
      problem but may adversely affect the kidney and hasten the progression to end
      stage renal disease. We conducted experiments to examine the impact of rhGH on
      the severity of chronic puromycin aminonucleoside (PAMN) nephropathy in rats. The
      glomerulopathy was induced by serial injections of PAMN over a 12 week period.
      Experimental animals (N = 6) received rhGH, 0.5 mg per dose, three times weekly,
      while control rats (N = 6) received hormone vehicle. rhGH had no effect on weight
      gain, hematocrit, or blood pressure in rats with the experimental renal disease.
      Urinary protein excretion increased approximately 50% in rhGH-treated rats with
      chronic PAMN nephropathy compared to untreated animals between four to eight
      weeks of the observation period. After 12 weeks, the inulin clearance was
      significantly lower in rhGH-treated rats, 0.26 +/- 0.05 versus 0.50 +/- 0.06
      ml/min/100 g body wt in control PAMN animals, P < 0.05. Compared to untreated
      rats with PAMN nephropathy, administration of rhGH increased the extent of
      segmental glomerulosclerosis from 11 +/- 3 to 46 +/- 9% (P < 0.005) and elevated
      the tubulointerstitial injury score from 0.5 +/- 0.1 to 1.4 +/- 0.4 (P < 0.05).
      Furthermore, glomerular hypertrophy was enhanced in animals with chronic PAMN
      nephropathy given rhGH, as evidenced by a larger glomerular planar area, 9.2 +/-
      0.3 x 10(-3) versus 11.9 +/- 0.5 x 10(-3) mm2, P < 0.005.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8301931
TI  - Detection of abnormal peripheral blood mononuclear cell cytokine networks in
      human IgA nephropathy.
AB  - Dysregulated cytokine expression has been implicated in the pathogenesis of IgA
      nephropathy, but the mechanisms and selectivity of this response are poorly
      understood. In this study we have examined the expression of a range of
      immunoregulatory cytokine mRNAs by peripheral blood mononuclear cells (PBMNCs)
      from 45 patients with IgA nephropathy stratified empirically according to urinary
      red cell excretion: 10 in remission, and 35 with active disease (21 mild, 14
      moderate), and 17 normal, and 15 disease, controls. We used a semi-quantitative
      polymerase chain reaction (PCR) technique. None of the patients had experienced
      recent episodes of macroscopic hematuria. Simultaneous analysis of monocyte class
      II antigen (DR) expression was also performed by two-color immunoflow cytometry.
      TGF-beta 1 mRNA was detected in 68% (24 of 35) of patients with active, and 70%
      (7 of 10) inactive IgA nephropathy, but in only 18% (3 of 17) normal (P < 0.005),
      and 27% (4 of 15) disease controls. IL-6 transcripts were identified in 37% (13
      of 35) of patients with active IgA nephropathy, compared with 6% (1 of 17) normal
      controls (P = 0.015), with no significant increase in IgA remission, or disease
      control groups. TNF-alpha mRNA was detected in 29% (5 of 17) of normal and 53% (8
      of 15) disease controls, but in only 7% (3 of 35) of patients with IgA
      nephropathy (P = 0.015). There was no significant change in TGF-beta 2, gamma
      IFN, IL-2, IL-4, IL-1 alpha or IL-1 beta detection between groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8301932
TI  - Cardiovascular consequences of correction of the anemia of renal failure with
      erythropoietin.
AB  - The purpose of this study was to define the physiologic responses of the heart
      and peripheral circulation to chronic anemia using noninvasive measurements while
      eliminating confounding biochemical, pharmacologic and physiologic variables.
      Stable chronic hemodialysis patients were studied at the University Hospital
      based chronic dialysis unit and echocardiography laboratory before and after
      therapy with human recombinant erythropoietin (rHuEPO). Subjects included
      maintenance hemodialysis patients free of left ventricular regional wall motion
      abnormalities discernible by echocardiography, rhythm disturbance, significant
      valvular or ischemic heart disease. Two-dimensional echocardiograms and
      simultaneous targeted M-mode echocardiograms, phonocardiograms and externally
      acquired subclavian artery pulse tracings were used to measure whole blood
      viscosity, arterial blood gases and ionized calcium, complete blood count,
      electrolytes, creatinine, blood urea nitrogen (BUN), and inorganic phosphate. All
      measurements were made immediately post-dialysis before and after therapy with
      rHuEPO. The interval between pre- and post-rHuEPO studies was 8.3 +/- 2.3 months.
      We found that post-dialysis hematocrit rose from 24.7 +/- 0.9 to 36.4 +/- 0.9%,
      hemoglobin from 83 +/- 3 to 121 +/- 3 g/liter and whole blood viscosity from 2.87
      +/- 0.11 to 3.71 +/- 0.18 centipoise (all, P < 0.001 after therapy with rHuEPO).
      The remaining biochemical measurements did not change. Heart rate fell from 83 +/
      3 to 77 +/- 3 beats/min (P = 0.013). Left ventricular preload and afterload were
      not statistically different before and after rHuEPO. Total vascular resistance
      rose from 1313 +/- 84 to 1568 +/- 129 dynes.sec.cm-5, P = 0.029. Cardiac output
      and cardiac index fell by 12 and 15% (P = 0.024 and 0.030),
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8301933
TI  - Differential splicing of COL4A5 mRNA in kidney and white blood cells: a complex
      mutation in the COL4A5 gene of an Alport patient deletes the NC1 domain.
AB  - PCR conditions were optimized to amplify the COL4A5 cDNA from lymphoblasts and
      kidney tissue. Sequencing of the COL4A5 mRNA isolated from the kidney of an
      Alport syndrome patient revealed two differences with the published sequence. One
      divergence, the insertion of an 18 bp sequence between exon 11 and 10 of the
      COL4A5 mRNA added two Gly-X-Y triplets to the COL4A5 sequence and was
      subsequently found in the mRNA of four normal kidney mRNA samples. This sequence
      was absent in all white blood cell RNA samples sequenced by us, indicating tissue
      specific splicing with the presence of an additional exon in kidney COL4A5 mRNA.
      This finding of differential splicing of COL4A5 mRNA in kidney and white blood
      cells might affect the use of white blood cell mRNA for the analysis of Alport
      mutations. Second, a complex mutation was detected in the mRNA from the AS
      patient introducing a premature stop codon in the message, deleting part of the
      triple helical domain and the complete NC domain. The mother of the patient was
      shown to be heterozygous for this mutation.

PMID- 8301934
TI  - HIV-associated immune-mediated renal disease.
AB  - Although focal glomerulosclerosis is the most common renal disease, other
      proliferative glomerulonephritides are encountered in HIV-infected patients. We
      studied four HIV-infected patients with renal insufficiency, proteinuria, and
      proliferative glomerulonephritis, consistent with immune-mediated disease, to
      investigate the role of the virus and immune complexes in the pathogenesis of the
      nephropathy. Circulating immune complexes (CICs) and HIV-reactive antibodies were
      measured and characterized in each patient. Renal biopsy tissue was acid eluted,
      and the eluate analyzed. DNA extracted from biopsies was subjected to the
      polymerase chain reaction (PCR) to detect HIV genome. CICs were detected in each
      patient: an IgA-p24 HIV antigen complex and an IgG antibody-gp 120 HIV antigen
      complex in two patients; two patients had an IgG-p24 HIV antigen complex.
      Identical complexes were eluted from renal tissue in the first three patients;
      p24 HIV antigen, and complement from the fourth. The eluted antibodies reacted
      with the HIV antigens from the isolated CICs. Direct immunofluorescence for viral
      antigen in the eluted glomerular tissue revealed HIV antigens; PCR confirmed the
      presence of gag genome in all four biopsies. We conclude both circulating and in
      situ HIV antigen-specific immune complexes may be associated with
      glomerulonephritis in HIV infected patients. Viral incorporation into renal
      tissue may be important in the pathogenesis of HIV-associated renal disease.

PMID- 8301935
TI  - Receptor-mediated uptake of IDL and LDL from nephrotic patients by glomerular
      epithelial cells.
AB  - Although hyperlipidemia is a well-recognized complication of the nephrotic
      syndrome, the precise interaction of human glomerular cells and human
      lipoproteins, abnormal in lipid and protein composition, has not been clearly
      defined. This study examines receptor mediated binding, internalization and
      degradation as well as intracellular cholesterol metabolism of apoB-100
      containing LDL and apoB,E containing IDL, isolated from patients with the
      nephrotic syndrome (N = 6), in human glomerular epithelial cells and skin
      fibroblasts. In the patients, serum LDL cholesterol level was increased threefold
      and IDL elevenfold as compared to healthy subjects. IDL of nephrotic patients
      contained 72% more cholesterol than IDL of healthy controls. No difference in
      lipid/protein composition was found in the LDL density range. Therefore,
      nephrotic and control LDL showed identical affinities for receptor mediated
      binding, internalization and degradation. Furthermore, inhibition of
      intracellular sterol synthesis and cholesteryl ester formation after incubation
      with LDL was comparable. In contrast, cholesterol-rich IDL of nephrotic patients
      was taken up by glomerular epithelial cells with higher affinity than LDL and
      control IDL, as well as intracellular sterol synthesis was suppressed more
      effectively than by control IDL. The cholesterol esterification rate of IDL from
      patients was enhanced 3.5-fold as compared to control IDL. In comparison to
      fibroblasts, glomerular epithelial cells showed about 15% of the maximal capacity
      for LDL uptake, but 31% for IDL from nephrotic patients. The data indicate that
      hypercholesterolemia of nephrotic origin cannot be explained by reduced ligand
      binding for LDL. ApoE containing IDL, which accumulate in nephrotic patients,
      were avidly taken up by glomerular epithelial cells via receptor dependent
      pathway. These lipoproteins could therefore play the predominant role in
      glomerular lipid accumulation and development of glomerulosclerosis.

PMID- 8301936
TI  - Hypertriglyceridemia and lowered apolipoprotein C-II/C-III ratio in uremia:
      effect of a fibric acid, clinofibrate.
AB  - We examined the effects of a fibric acid, clinofibrate, on lipoprotein metabolism
      in 12 hyperlipidemic patients with uremia treated on continuous ambulatory
      peritoneal dialysis during a 24 week treatment. Daily dose of clinofibrate was
      200 mg for the initial four weeks, 400 mg for the second four weeks, and 600 mg
      for the subsequent 16 weeks. Serum and very-low density lipoprotein (VLDL)
      triglyceride were decreased by 36% and 48%, respectively. Neither total
      cholesterol nor apolipoprotein B changed significantly, whereas cholesterol was
      decreased in VLDL and increased in low (LDL) and high density lipoprotein (HDL)
      fractions. Post-heparin plasma lipoprotein lipase (LPL) before treatment was not
      lower than the normal value, and we found no change in LPL activity following
      clinofibrate. Hepatic triglyceride lipase also did not change. Apolipoprotein
      (apo) C-II/C-III ratio was low as compared to the normal value before treatment,
      and the ratio was increased by 38% after the treatment. Decrease in VLDL
      triglyceride was associated with increase in apo C-II/C-III ratio in all the
      cases. Abnormal enrichment with triglyceride of LDL and HDL fractions was
      improved by clinofibrate. Although one patient had a transient and asymptomatic
      elevation of serum creatine phosphokinase, no patient had muscle pain. There was
      no accumulation of the drug in the 24 week trial. These results suggest that
      clinofibrate is an effective and safe approach to the management of dyslipidemia
      in CAPD patients.

PMID- 8301937
TI  - Free and protein-bound tryptophan in serum of untreated patients with chronic
      renal failure.
AB  - In fasting sera from 46 untreated patients with chronic renal failure and in 22
      normal subjects, non-protein-bound tryptophan, F, was separated by pH-controlled
      equilibrium dialysis. Total tryptophan, T, and F were measured by HPLC. Results
      in patients were related to gender, severity of chronic renal failure (as
      measured by radioisotopic glomerular filtration rate), protein intake (as
      measured by 24-hr urinary urea N excretion), and protein nutrition (as measured
      by serum concentrations of albumin and transferrin). T was subnormal in 59% of
      the patients. In seven hypoalbuminemic patients, F/T was markedly increased
      (approaching unity) but F was normal. In 39 non-hypoalbuminemic patients, F was
      again normal but F/T was often increased at glomerular filtration rates below 30
      ml/min/3 m2 of height2, especially in females. T was significantly correlated
      with estimated protein intake (r = 0.54, P = 0.0004), even though neither F nor
      serum protein levels were correlated with it. We conclude that the serum level of
      free tryptophan is well-maintained in chronic renal failure, being uninfluenced
      by severity of renal insufficiency, voluntary protein intake, or serum protein
      concentrations. On the other hand, protein-bound tryptophan varies with protein
      intake, decreases markedly in hypoalbuminemic patients, and also decreases in
      many nonhypoalbuminemic patients (especially females) when the glomerular
      filtration rate falls below approximately 30 ml/min/3 m2 of height2.

PMID- 8301938
TI  - In situ hybridization and localization of mRNA for the rabbit prostaglandin EP3
      receptor.
AB  - The physiological effects of PGE2 appear to be mediated by at least three
      different "E-prostanoid" receptors designated EP1,EP2, and EP3. These receptors
      are differentially activated by structural PGE analogs (such as misoprostol) and
      each couples to a different signal transduction mechanism. Studies demonstrating
      that inhibition of water absorption in the collecting duct is mediated by a Gi
      coupled mechanism, suggests that an EP3 receptor is involved the renal effects of
      PGE2. We used in situ hybridization to determine the tissue distribution of the
      rabbit EP3 receptor. [alpha-35S] UTP labeled antisense RNA, comprising
      transmembrane domains IV through VII, was hybridized to tissue sections. Specific
      labeling of kidney, stomach and adrenal was observed. In the kidney, medullary
      thick ascending limb and cortical and medullary collecting ducts were intensely
      labeled, while no labeling of glomeruli, proximal tubules, or cortical thick
      ascending limbs was observed. The adrenal gland labeled exclusively in the
      medulla. In the stomach the gastric epithelial crypts were the predominant site
      of hybridization, without evidence of labeling of the smooth muscle. These
      results suggest an important role for the EP3 receptor in mediating PGE2 effects
      in these tissues.

PMID- 8301939
TI  - Use of angiotensin-converting-enzyme inhibitors for diagnosing renovascular
      hypertension.

PMID- 8301940
TI  - [Long-term results of the surgical treatment of stomach ulcer].
AB  - The results of surgical treatment of 384 patients with gastric ulcer disease
      within the follow-up period of 1 to 10 and more years have been analysed. Two
      hundred and fifty patients underwent gastric resection, 85--organ-preserving
      operation with vagotomy, 49--closure of a perforative ulcer. On the basis of data
      of clinico-functional investigations, the advantages and disadvantages of the
      methods of surgical treatment used have been studied.

PMID- 8301941
TI  - [Surgical treatment of patients with complicated duodenal ulcer and duodenal
      stasis].
AB  - On the basis of analysis of the results of surgical treatment of 488 patients
      with a perforative ulcer, 314--with a bleeding one, and 118--with penetrating
      pyloroduodenal ulcer, impairment in motor-evacuatory duodenal function was
      established in 12.8% of cases. A conclusion was made about the necessity to
      correct this disorders, indications for the operation for duodenostasis in
      complicated ulcer disease were substantiated.

PMID- 8301942
TI  - [Curative enterocutaneous fistula in emergency abdominal surgery].
AB  - Results of the use of a curative enterocutaneous fistula in 87 patients with
      acute ileus and diffuse forms of peritonitis have been analysed. In 66 (79%)
      patients, the formation of fistula was performed in addition to the main stage of
      the operation, in 17 (21%)--as an independent intervention. In 4 patients, a
      fistula was intended for enteral feeding, in 66--for temporal unloading of the
      intestine, in 14--for total exclusion of passage of the intestinal content and
      permanent decompression of the intestine.

PMID- 8301943
TI  - [Surgical treatment of elderly patients with acute cholecystitis].
AB  - The experience with surgical treatment of 136 elderly and senile patients with
      acute cholecystitis has been summarized. In presence of pronounced concomitant
      pathology and reduced adaptation-compensatory resources of an organism, the
      authors consider microcholecystostomy to be a method of choice. The use of this
      method permits to improve the results of surgical treatment and decrease the
      postoperative lethality.

PMID- 8301944
TI  - [Surgical treatment of patients with cholestatic hepatitis].
AB  - The experience with treatment of 86 patients with cholestatic form of hepatitis
      has been summarized. The operative intervention included drainage of the
      extrahepatic bile ducts, denervation of the hepatoduodenal ligament, marginal
      hepatic resection. In ineffective conservative therapy, the patients should be
      operated on at the early period. When establishing the indications for the
      operation, the functional state of hepatocytes should be considered.

PMID- 8301945
TI  - [Blunt and penetrating injuries of gallbladder and extrahepatic bile ducts].
AB  - The authors observed 23 sufferers with closed and open injuries to the
      gallbladder and extrahepatic bile ducts. Trauma to the gallbladder was revealed
      in 20, that to the common bile duct--in 3, associated injuries--in 18 sufferers.
      In injury to the gallbladder, cholecystectomy was performed. The organ-preserving
      operation is justified only in presence of a small cut wound without disturbance
      of blood circulation of the organ. In trauma to the common bile duct, the end-to
      end biliobiliary anastomosis was created over a removable transhepatic drain
      (RTHD), and when it's creation was unfeasible, hepaticojejunostomy over RTHD was
      performed.

PMID- 8301946
TI  - ["Siphon" structure of the digestive system and a method for "siphon" one-stage
      terminal lateral small-to-large intestine anastomosis with invagination].
AB  - The authors have suggested a hypothesis according to which the alimentary canal
      consists of the separate autonomous S-shaped functional structures possessing the
      antireflux and sphincter-like properties. The principle mentioned was used in 9
      patients who had a "siphon" one-story invagination small-to-large intestinal
      anastomosis been created.

PMID- 8301947
TI  - [Prophylaxis of surgical wound suppuration in patients with acute intraabdominal
      diseases].
AB  - The experience with treatment of 2512 patients with acute diseases of the
      abdominal organs permitted the authors to draw a conclusion that the local
      measures are of primary importance in prevention of suppuration of an operative
      wound. Of these measures, the main ones are the following: observance of the
      surgical technique, differential draining the wound with the use of a drainage
      tube of original construction, dynamic control of a state of the wound after the
      operation. The use of the measures mentioned permitted to reduce the incidence of
      suppuration of an operative wound from 8.2 to 4.8%.

PMID- 8301948
TI  - [Early diagnosis of acute postoperative renal insufficiency].
AB  - A method for diagnosis of the initial manifestations of acute renal failure based
      on the principle of mathematic modelling of medical diagnosis has been developed.
      The effectiveness of the method is 98%.

PMID- 8301949
TI  - [Combined selective proximal vagotomy in the surgical treatment of duodenal
      ulcer].
AB  - Preservation of adequate blood supply to a gastric wall and resistance of mucosa
      of the gastroduodenal region with simultaneous full-value parasympathetic
      denervation of its acid-producing zone in performance of selective proximal
      vagotomy contributes to decrease in incidence and pronouncement of ischemic
      disorders in motor-evacuatory function of the stomach at the early postoperative
      period, effective and stable reduction in acid production, shortening of duration
      of the postoperative treatment and rehabilitation of the patients, prophylaxis of
      ulcer recurrences.

PMID- 8301950
TI  - [New radiocontrast media].
AB  - On the basis of the use of anomal effects of X-radiation interaction with the
      media containing ultradispersed particles of some metals and their oxides with
      the sizes under 1 mm, the authors have suggested radiopaque material.

PMID- 8301951
TI  - [Postoperative electromyographic monitoring of small intestine function in
      patients with peritonitis and acute intestinal obstruction].
AB  - In 49 patients with general peritonitis and acute ileus, the authors used the
      method of direct electromyography. On the basis of analysis of the results, the
      functional state of the intestine, dynamics of its motor activity, effectiveness
      of the treatment performed were assessed and outcome of the disease was
      predicted.

PMID- 8301952
TI  - [Effect of some drugs on the intensity of lipid peroxidation in surrounding
      tissues in the local treatment of suppuration].
AB  - The effect of some drugs in their local use for treatment of purulent wounds on
      the intensity of peroxide oxidation of lipids in the perifocal tissues of an
      experimental suppurative focus was studied. The increased antioxidant and
      antiinflammatory effect in use of lyposomal form of gentamycin with the
      ectericide-modified membranes versus ectericide solution as well as more
      pronounced antioxidant and antiinflammatory effect of ferecterisole vs. cimesole
      was revealed. The results obtained indicate that the use of ferecterisole and
      lyposomal forms of some antibiotics for local treatment of purulent wounds has
      good prospects.

PMID- 8301953
TI  - [Immediate results of surgical treatment of gastric stump cancer].
AB  - An immediate result of surgical treatment of gastric stump cancer in 68 patients
      is presented. The resectability rate was 23.5%. Lethality after radical
      operations was 18.7%, after symptomatic operations and exploratory laparotomy
      9.6%. Gastric resection was performed, using the method developed in the clinic
      with wrapping the anastomosis, or gastric stump by a loop of the afferent
      intestine. In development of gastric stump cancer, local spreading of a tumor is
      not a reason to discard performance of radical operation.

PMID- 8301954
TI  - [Methodologic errors in subtotal stomach resection for gastric cancer].
AB  - In 395 patients with gastric cancer, the subtotal distal resection of the stomach
      was performed at the oncologic dispensary. In 47.6% of cases, a blunder in
      ablasticity of operation was committed. Distal resection of the stomach was
      unreasonably performed in patients with involvement of the middle gastric portion
      and in infiltrative tumour growth.

PMID- 8301956
TI  - [Osteotomy of the humerus in the operative treatment of children with
      complications of obstetrical Duchenne-Erb paralysis].
AB  - From 1987 to 1991, 33 children with sequelae to Duchenne--Erb type obstetrical
      paralysis of an upper extremity were operated on in the clinic. In 20 patients,
      the operations were performed on the tendinomuscular apparatus of the humeral
      articulation, in 13--on the humerus. The technique for performance of detorsive
      osteotomy of the humerus is described. Indications for the given method of
      operative rehabilitation are substantiated.

PMID- 8301955
TI  - [Radiography as a criterion for evaluation of treatment results in chronic
      hematogenic osteomyelitis of the long bones].
AB  - The findings of roentgenologic observation of the patients for 4 years after
      plasty of the residual cavity of dura mater of the brain are presented. A good
      long-term result was noted in 85.7% of the patients.

PMID- 8301957
TI  - [Repair of posttraumatic hand defects in children].
AB  - The experience with the use of a method of distraction for reconstruction of 98
      digits in 37 patients with amputation defects has been summarized. Lengthening of
      the digits by 3-7 cm was achieved. This permitted to improve considerably the
      function and cosmetic appearance of a damaged hand.

PMID- 8301958
TI  - [Comparative assessment of methods in early diagnosis of acute hematogenic
      osteomyelitis in children].
AB  - The results of early diagnosis of acute hematogenous osteomyelitis in 329
      children were analysed, causes of diagnostic errors and late hospitalization
      studied. A comparative assessment of diagnostic potentialities of liquid crystal
      termography (142 cases), osteotonometry and cytologic of a punctate of medullar
      cavity (89), osteomedullography (65), intraosseous thermometry (75) and
      roentgenography of the bones. Use of liquid crystal thermography permitted to
      establish location and spreading of the inflammatory process in a bone at the
      first day of the disease, to control the effectiveness of treatment, to predict
      its course and outcome.

PMID- 8301959
TI  - [Changes of hemodynamics and microcirculation in ultraviolet blood irradiation
      for experimental peritonitis].
AB  - It was established that resulting form ultra-violet irradiation of the blood in
      peritonitis, the pulse increased, diastolic and systolic arterial pressure didn't
      decreased. The intensity of tissue blood flow increased, especially in the
      mesentery. This was caused by considerable increase in volumetric blood flow rate
      in the mesenteric artery.

PMID- 8301960
TI  - [The concept of standard for pathologic state (exemplified in peritonitis)].

PMID- 8301961
TI  - [Venous blood circulation disorders of the abdominal organs].

PMID- 8301962
TI  - [Clinical pharmacology of aminoglycosides and their role in the prophylaxis and
      treatment of surgical infection].

PMID- 8301963
TI  - [Endolymphatic therapy in acute appendicitis].

PMID- 8301965
TI  - [Antibiotics in abdominal surgery].

PMID- 8301964
TI  - [Recurrence of uncomplicated duodenal ulcer after surgical treatment].
AB  - A 10-year result of surgical treatment of 187 patients with an uncomplicated
      duodenal ulcer has been analysed. Gastric resection was performed in 92 patients,
      the different types of vagotomy--in 95. After gastric resection, a peptic ulcer
      of gastroenteroanastomosis occurred in 1 patient, after vagotomy--in 28. The
      author considers vagotomy to be insufficiently effective in the treatment of an
      uncomplicated duodenal ulcer. It is not expedient to extend the indications for
      surgical treatment of the patients with uncomplicated duodenal ulcer.

PMID- 8301966
TI  - [Agenesis of the gallbladder complicated with choledocholithiasis].

PMID- 8301967
TI  - [Diagnosis of the torsion of colonic omental processes].

PMID- 8301968
TI  - [Torsion of the epiploic process of the sigmoid colon].

PMID- 8301969
TI  - [Local use of a drug combination consisting of fluorouracil, cyclophosphamide and
      silicone sorbent in patients with colonic cancer].

PMID- 8301970
TI  - [Thromboembolism in a child with severe burns].

PMID- 8301971
TI  - [Preservation of an upper extremity in a patient with severe late complications
      of reconstructive surgery for shoulder trauma with major artery injury].

PMID- 8301972
TI  - [Foreign body in the soft tissues of the neck].

PMID- 8301973
TI  - [A case of esophageal papilloma located in a diverticulum].

PMID- 8301974
TI  - [Combined gunshot injury of the abdominal cavity and vertebral column with a
      locksmith drill].

PMID- 8301975
TI  - [Factors of natural resistance in the surgical treatment of gastric and duodenal
      ulcer].
AB  - In examination of 42 patients with gastric and duodenal ulcer disease, the
      disorders in cellular and humoral immunity were revealed. The immunologic indices
      didn't normalize under the influence of the operative treatment. This is
      indicative of the necessity to perform the immunocorrigative therapy before the
      operation.

PMID- 8301976
TI  - [False "acute abdomen" and acute gastric hemorrhage in diabetes mellitus].

PMID- 8301977
TI  - [Graft-versus-host disease].

PMID- 8301978
TI  - [Blood levels of 6-keto-prostaglandin F1alpha, thromboxane and prostaglandin
      F2alpha in patients with bronchial asthma].
AB  - The study revealed the relation of bronchial asthma (bacterial variant) clinical
      pattern to plasma levels of PGF2 alpha, 6-keto-PGF1 alpha and TxB2. In remission
      of the disease the above indices are lower. Severe asthma remission is
      characterized by higher levels of 6-keto-PGF1 alpha and TxB2 than moderate asthma
      one, demonstrates a tendency to growing PGF2 alpha levels. A rise in PGF2 alpha
      and TxB2 in manifest asthma points to their participation in bronchospasm
      formation suggesting an active role of these bronchoconstrictors in asthma
      pathogenesis. Higher levels of 6-keto-PGF1 alpha are of a compensary nature in
      the pathogenesis of PGF2 alpha and TxB2 bronchoconstrictory action, and of
      damaging nature contributing to the formation of bronchial mucosa edema and
      bronchial gland hypersecretion.

PMID- 8301979
TI  - [Treatment of simultaneous episodes of angina and respiration disorders].

PMID- 8301980
TI  - [Treatment of patients with stable angina by combination of trinitrolong and
      propranolol].
AB  - Trinitrolong (TNL), a long-acting nitroglycerin for application on the gingiva,
      was comparatively assessed for effect on stable angina pectoris in monotherapy
      and in combination with beta-adrenoblocker propranolol. A total of 11 anginal
      patients received the combination the efficacy of which was verified by paired
      bicycle ergometry. A high antianginal effect of TNL was established. However, its
      combination with propranolol entails neither higher exercise tolerance nor less
      frequent anginal attacks. An increment in the effect was not seen either when the
      combination was used in single and course doses in one-third of the patients.

PMID- 8301981
TI  - ["Innocent" heart murmurs].
AB  - The paper presents the review of the literature data and the results of the
      authors' own experience in the aspects of the origin and clinical interpretation
      of "innocent" cardiac murmurs (ICM). It was suggested that ICM were a regular
      phenomenon in the majority of the young people. Contradictions in current views
      on the problem of ICM appearance were discussed from the point of view of the
      leading importance of disproportion in the development of the major vessels and
      cardiac cavities, systolic regurgitation at atrioventricular valvular
      dysfunction, hyperkinetic cardiac effects. The paper presents the data which
      permit one to consider morphofunctional features of intracardiac structures
      violating the uniformity and equality in the cardiac release tracts as leading
      causes of ICM appearance. Pathogenetic unity of ICM and organic murmurs was
      distinguished as the manifestation of murmuring turbulent flows. Principle
      difference between the leading mechanisms of these murmurs occurrence was
      discussed as well.

PMID- 8301982
TI  - [Structural and functional characteristics of thrombocytes in chronic ischemic
      heart disease].
AB  - Platelets from 103 patients with chronic coronary heart disease were studied
      electron microscopically, cytochemically, fluorescence microscopically and with
      radionuclides. The platelets showed polymorphism indicated by diverse sizes,
      various content of alpha-granules in platelets, emergence of degenerative
      hyperosmiophilic forms. Shorter life cycle of the platelets was observed in line
      with a compensatory increase in the number of their immature forms. Abundance of
      reversibly and irreversibly activated and degranulated cells impaired platelet
      aggregation. These changes entailed rearrangement of platelet glycocalyx. The
      findings evidence noticeable structural shifts in platelets which diminish their
      resistance to factors stimulating atherogenesis and underlying aggravations of
      coronary heart disease.

PMID- 8301983
TI  - [Current chronotherapy].

PMID- 8301984
TI  - [A method of intensive therapy for atrial flutter].
AB  - The authors propose a new stepwise method of intensive therapy of atrial flutter
      (AF) based on atrial transesophageal pacing (ATEP) the efficacy of which was
      raised by previous digitalization. Patients of group 1 (n = 25) were scheduled to
      have ATEP, in its inefficacy ATEP was to be followed by antiarrhythmic drugs and
      on-demand cardioversion. In patients of group 2 (n = 27) ATEP was preceded by
      digitalization. ATEP and antiarrhythmic chemotherapy resulted in restoration of
      the sinus rhythm in 48% of the cases, cardioversion was performed in 11 patients
      of group 1. In group 2 normal rhythm was reestablished in 88% of the patients, 2
      patients experienced cardioversion. The proposed variant of treatment is
      advocated as an alternative to cardioversion.

PMID- 8301985
TI  - [Effectiveness of low-energy laser treatment of patients with recurrent chronic
      gastrointestinal erosions].

PMID- 8301986
TI  - [Anemic syndrome in chronic hepatitis and liver cirrhosis].
AB  - Regularities in the development of anemia in patients with chronic hepatitis or
      hepato-cirrhosis were studied with regard to the pattern and stage of the
      affection of the liver. The impact of inefficient erythropoiesis on anemia
      development in patients with chronic diffuse diseases of the liver was
      demonstrated. Reasons of the red cells imperfection that caused their rapid
      hemolysis were indicated. In the bone marrow of chronically ill patients there
      were lower levels of early precursors of erythropoiesis with their proliferative
      activity reduced. On the basis of the data obtained the authors gave practical
      recommendations for anemia treatment.

PMID- 8301987
TI  - [Plasmapheresis in the combined treatment of rheumatoid arthritis, complicated
      with anemia and blood coagulation disorders].
AB  - Time course of changes in hemostasis were investigated in 68 rheumatoid arthritis
      (RA) patients. DIC syndrome and anemia were recorded in 23 and 20 patients,
      respectively. Three RA sufferers were free of anemia. A course of plasma-pheresis
      proved effective against DIC syndrome in 12 anemic and 2 nonanemic patients.
      Alleviation of DIC syndrome occurred in association with improvement in the red
      cell count and inhibition of rheumatoid process activity. In persistent DIC
      syndrome a trend to normalization of the above parameters was insignificant.

PMID- 8301988
TI  - [Reaferon ++ and antioxidants effectiveness in chronic salmonellosis and bacteria
      carrier state].

PMID- 8301989
TI  - [Longevity, atherosclerosis and cellular immunity].

PMID- 8301990
TI  - [Lymphangiosarcoma in postmastectomy arm lymphostasis of the arm (Stewart-Treves
      syndrome)].

PMID- 8301991
TI  - [Neurosyphilis complicated with craniocerebral nerve disorders].

PMID- 8301992
TI  - [Use of erythrocyte mass in clinical practice].

PMID- 8301993
TI  - [Various mushroom poisonings].

PMID- 8301994
TI  - [Anemia: diagnostic algorithm].

PMID- 8301995
TI  - [Is the current level of gastroenterologic diagnosis satisfactory?].

PMID- 8301996
TI  - [Doctor Diadkovsky and Lermontov, the poet].

PMID- 8301997
TI  - [Role of the clinical departments in the establishment of the pathoanatomy
      department in the Moscow University].

PMID- 8301998
TI  - [Interdisciplinary practice. Necessity and difficulties].

PMID- 8302000
TI  - [Migration and maternity. Resonances of exile].

PMID- 8301999
TI  - [Reviewing the structures of maternity wards. For the care of mother-father
      children].

PMID- 8302001
TI  - [Preventing unemployment of nurses, counsel the jobless patient: looking for the
      1. job].

PMID- 8302002
TI  - [Clarification of the concepts of health and disease for health care. After all,
      what is health?].

PMID- 8302003
TI  - [Project report on the topic of nursing relations. How relations could be
      improved].

PMID- 8302004
TI  - [Computers coming to the bedside].

PMID- 8302005
TI  - [The DW project at the Zurich University HospitaL. Collective guidance, decision
      sharing of the team].

PMID- 8302006
TI  - [Is there solidarity among women?].

PMID- 8302007
TI  - [A study of the situation of nursing teachers in practice: nursing coach,
      clinical teacher or tutor?].

PMID- 8302008
TI  - [My workplace. Diagnosis: drunk].

PMID- 8302009
TI  - [Kinesthetics--an efficient method. Tridimensional movement--complete cure].

PMID- 8302010
TI  - [Treatment and rehabilitation centers. Quality before everything].

PMID- 8302011
TI  - Are the nonmitochondrial peripheral benzodiazepine receptors on leukocytes a
      novel intermediary of brain, behavior, and immunity?

PMID- 8302012
TI  - Increased expression of neprilysin (neutral endopeptidase 24.11) in rat and human
      hepatocellular carcinomas.
AB  - BACKGROUND: Neprilysin (EC 3.4.24.11) (NEP), a membrane metallopeptidase, is
      identical with common acute lymphoblastic leukemia antigen or cluster
      differentiation antigen 10. This antigen is present in blast cells in acute
      lymphoblastic leukemias and is implicated in differentiation of B lymphocytes.
      NEP cleaves a variety of peptides including bradykinin, substance P, bombesin,
      enkephalins, and atrial natriuretic peptide. We investigated its expression in
      several variants of rat hepatomas and a human hepatocellular carcinoma cell line.
      Normal rat and human livers were used as controls. EXPERIMENTAL DESIGN: The
      expression of NEP (common acute lymphoblastic leukemia antigen) was determined
      with: (a) enzyme assays; (b) high performance liquid chromatography analysis of
      bradykinin metabolism; (c) immunoprecipitation; and (d) mRNA characterization.
      RESULTS: NEP activity increased by 2 to 3 orders of magnitude in all rat
      hepatomas and in the human SK-HEP1 cell line, compared with normal tissues.
      Antiserum against rat NEP precipitated 93% of endopeptidase activity in rat
      hepatomas, whereas monoclonal antibody to common acute lymphoblastic leukemia
      antigen immunoprecipitated 99% of that in human hepatocarcinoma cells.
      Solubilized rat hepatoma membranes cleaved bradykinin to a hepta- and dipeptide;
      the reaction was inhibited by an NEP inhibitor. Activity of three other membrane
      peptidases did not increase in rat hepatomas. Northern hybridization revealed the
      presence of NEP mRNA in rat hepatoma, but not in normal liver. Reverse
      transcriptase-polymerase chain reaction showed that hepatomas have higher amounts
      of NEP mRNA than normal liver of the same strain. CONCLUSIONS: Rat hepatomas and
      a human hepatocarcinoma cell line express high amounts of NEP, in contrast to
      normal rat and human livers, which have very little. The increase in NEP activity
      could be due to increased transcription by tumor cells and may signal malignant
      transformation of liver cells.

PMID- 8302013
TI  - Immunohistochemical and genetic characterization of the M Cagliari alpha-1
      antitrypsin molecule (M-like alpha-1-antitrypsin deficiency).
AB  - BACKGROUND: Genetic alpha-1-antitrypsin (AAT) deficiency may be due to defective
      secretion, intracellular degradation, or lack of synthesis. Defective secretion
      results in hepatocytic storage and liver disease. These two events occur only
      with the common deficiency variant, Z AAT, and with a few rare deficiency
      variants, called M-like. Hepatocytic storage of AAT (either Z or M-like) can be
      demonstrated in tissue sections by specific immunostaining with a polyclonal anti
      AAT antibody, that recognizes all variants of AAT. A monoclonal antibody capable
      of selectively and exclusively reacting with Z AAT has been generated and
      successfully used in both serum and tissue studies. EXPERIMENTAL DESIGN: To
      determine whether a new M-like variant, M Cagliari, carries a mutation different
      from Z AAT, we have compared antigenic properties and DNA sequences of the two
      variants. Liver tissue sections from PiZ and PiM Cagliari patients were stained
      with both polyclonal anti-AAT and monoclonal anti-Z AAT antibodies. DNAs were
      polymerase chain reaction-amplified with AAT-specific primers and sequenced.
      RESULTS: Liver tissue sections from PiZ livers were positively stained with
      either the polyclonal or the monoclonal antibody. The PiM Cagliari liver sections
      reacted with the polyclonal antibody, but not with the monoclonal anti-Z AAT,
      thus indicating a difference in antigenicity from Z AAT. Accordingly, DNA
      analysis ruled out a Z mutation and revealed a microdeletion in exon II,
      identical with M Malton. CONCLUSIONS: A simple immunohistochemical assay based
      upon the application of both polyclonal and monoclonal antibodies represents a
      reliable test to distinguish Z and nonZ AAT deficiencies, thus assisting in the
      selection of cases worthy of more time-consuming analyses such as DNA sequencing.
      The same approach may be used for the characterization of as yet undefined PiM
      cases with AAT liver storage.

PMID- 8302014
TI  - Advances in flow cytometry for diagnostic pathology.

PMID- 8302015
TI  - Subcellular localization of peripheral benzodiazepine receptors on human
      leukocytes.
AB  - BACKGROUND: The peripheral-type benzodiazepine receptor (PBR) was initially
      identified in many peripheral tissues and in some blood cells. Drugs that bind
      with high affinity to PBRs have previously been described as having
      immunomodulating properties. The number of PBRs varies according to the cell
      population considered. The aim of this study was to study the localization of
      PBRs in two human leukocyte populations, T4-lymphocytes, and monocytes.
      EXPERIMENTAL DESIGN: Both cell populations were purified by negative
      immunoselection in order to keep only the physiologically accessible sites on the
      viable cells. Mitochondria were quantified by electron microscopy and flow
      cytometric analysis. Subcellular localization was then studied after PBR
      photoaffinity labeling using electron microscopic ultrastructural
      autoradiography. RESULTS: We have shown that monocytes contain twice as many
      mitochondria as lymphocytes. We have also shown that the global labeling of
      monocytes by ultrastructural autoradiography is actually higher than that of
      lymphocytes and the labeling of monocyte mitochondria is higher than that of
      lymphocyte mitochondria. In addition, the distribution of subcellular labeling
      indicates that there are different populations of mitochondria in one cell, i.e.,
      labeled and unlabeled, and that the percentage of labeled mitochondria is greater
      in monocytes. These results are consistent with those obtained in previous
      binding studies. Finally, over 50% of receptors are localized in cell
      compartments devoid of visible mitochondria. CONCLUSIONS: The subcellular
      distribution of the PBR shows that this receptor could have other physiologic
      functions towards immune cells than a function associated with mitochondria.

PMID- 8302016
TI  - Lithium chloride suppresses the synthesis of messenger RNA for infected cell
      protein-4 and viral deoxyribonucleic acid polymerase in herpes simplex virus-1
      infected endothelial cells.
AB  - BACKGROUND: Patients treated with lithium salts for manic depression had a lower
      incidence of herpes simplex infections. Initial studies in our laboratory
      demonstrated that addition of LiCl in cultures of human endothelial cells
      infected with herpes simplex virus suppressed viral replication and allowed
      synthesis of host proteins. EXPERIMENTAL DESIGN: Based on the above observations,
      we decided to study the optimal condition for the lithium effect and determine
      the process of inhibition of viral replication. Endothelial cell cultures
      infected with herpes simplex virus-1 were exposed to LiCl at various times
      postinfection. The levels of host and viral mRNAs were measured by Northern and
      slot blot hybridization. The pattern of protein synthesis was analyzed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot and replication
      was assessed by plaque assay. RESULTS: LiCl inhibited virus replication in a dose
      and time-dependent manner as was reflected in the sharp decrease or absence of
      infectious virus production. The condition for optimal effects of LiCl were the
      addition of the salt between 0-3 hours postinfection, and at a concentration of
      30 mM. LiCl suppressed the synthesis of viral polypeptides, whereas the synthesis
      of host proteins was maintained. Similar results were observed with
      phosphonoacetic acid, an inhibitor of viral DNA polymerase. NaCl, at the same
      concentration as LiCl, did not prevent the virus-induced inhibition of host cell
      protein synthesis. The level of host mRNA for fibronectin, thrombospondin,
      collagen type IV, actin, and plasminogen activator inhibitor-1 were maintained in
      the presence of LiCl. mRNAs for viral proteins, ICP-4 and DNA polymerase were
      nearly undetectable when LiCl was added with the virus (0 time postinfection).
      CONCLUSIONS: The data indicate that LiCl treatment results in suppression of
      herpes virus mRNAs, i.e., mRNAs for ICP-4 and DNA polymerase, thereby inhibiting
      replication. On the other hand, the levels of host mRNAs are maintained to
      varying degrees depending on the message. The data suggest that a very early step
      in the process of viral replication is affected by LiCl, since the drug is
      maximally effective when added with the virus.

PMID- 8302017
TI  - The blood-retinal barrier in experimental autoimmune uveoretinitis. Leukocyte
      interactions and functional damage.
AB  - BACKGROUND: In posterior uveitis the blood-retinal barrier (BRB) plays an
      important role in the pathogenesis of the disease. However, the morphologic
      correlate of BRB breakdown and the route of leukocyte migration remain poorly
      defined. EXPERIMENTAL DESIGN: Using an experimental model of autoimmune
      uveoretinitis in the rat, we have examined the ultrastructural alterations and
      leukocyte interactions occurring at the BRB. By employing electron-dense tracers,
      the development of BRB breakdown, and the route of extravasation were
      investigated. RESULTS: No increase in BRB permeability was found before
      lymphocytic infiltration. At day 10 postimmunization with retinal-soluble antigen
      and beyond, inflammatory cells could be seen within the retina that was quickly
      followed by an extensive increase in the permeability of the retinal vasculature
      to lanthanum and horseradish peroxidase. Occasionally, horseradish peroxidase
      reaction product could be seen extending throughout the 'tight junctions' of the
      retinal endothelia, but not those of the retinal pigment epithelia. Inflammatory
      cells, particularly mononuclear cells, were seen forming perivascular cuffs and
      extending posteriorly towards the outer retina. Retinal damage was initially
      restricted to the outer nuclear and photoreceptor layers that were in close
      proximity to these vessels. Leukocytes could be seen adhering to the retinal
      vessels and penetrating the endothelial cell cytoplasm close to tight junctions,
      but were never seen probing the junctions directly. At the retinal pigment
      epithelium, however, there was little evidence of migration into the retina
      during the early stages of the disease, even though the choroid often became
      packed with inflammatory cells. At later stages, occasional inflammatory cells
      could be seen between, and apparently within, retinal pigment epithelium cells in
      areas overlying sites of severe choroidal infiltration. CONCLUSIONS: The prime
      site of leukocyte infiltration and damage to the BRB in autoimmune uveoretinitis
      occurred at the level of the vascular endothelia and that diapedesis takes place
      primarily via an intraendothelial process.

PMID- 8302018
TI  - Activated neutrophils from rat injured isolated hepatocytes.
AB  - BACKGROUND: Activated neutrophils (PMNs) release cytotoxic agents that can damage
      surrounding tissue. These studies were performed to determine whether activated
      PMNs from rat could injure isolated, rat hepatic parenchymal cells (HCs) in
      vitro. EXPERIMENTAL DESIGN: HCs were cocultured with unstimulated rat PMNs or
      with PMNs activated with either f-met-leu-phe (FMLP) or phorbol myristate acetate
      (PMA), that stimulate predominantly degranulation or superoxide production,
      respectively. Toxicity to HCs was evaluated from release of alanine
      aminotransferase into the medium. RESULTS: Alanine aminotransferase release was
      greater in HCs cocultured with FMLP- or PMA-stimulated PMNs compared with
      unstimulated PMNs. Toxicity was observed by 16 hours after stimulation of PMNs.
      To test the possible involvement of a soluble mediator released by activated
      PMNs, HCs were incubated with conditioned medium from PMNs. Compared with
      unstimulated PMNs, toxicity to HCs was greater in the presence of conditioned
      medium from FMLP-stimulated PMNs, but not conditioned medium from PMA-activated
      PMNs. Reactive oxygen species do not appear to be involved in the mechanism by
      which activated PMNs damage HCs since superoxide dismutase, catalase, superoxide
      dismutase+catalase, or desferrioxamine failed to prevent the injury. Furthermore,
      less superoxide anion was detected in PMA-stimulated PMNs when either HCs or HC
      conditioned medium was present. Proteolytic enzymes released by stimulated PMNs
      may play a role in HC damage since an inhibitor of proteases diminished injury
      due to PMNs activated by either FMLP or PMA. CONCLUSIONS: These results indicate
      that activated, rat PMNs damage HCs in culture. The data suggest that reactive
      oxygen species are not involved in the mechanism, but that release of proteolytic
      enzymes may play a role in the toxic response.

PMID- 8302019
TI  - Maturation arrest of stem cell differentiation is a common pathway for the
      cellular origin of teratocarcinomas and epithelial cancers.
AB  - Analysis of the cellular origin of carcinomas of different organs indicates that
      there is in each instance, a determined stem cell required for tissue renewal
      that is the cell of origin for carcinomas. The normal tissue-determined stem
      cells are the result of differentiation in the embryo and are little changed, if
      at all, from the embryonic cells. Malignant stem cells are derived from these
      normal stem cells of adult tissues. The resultant tumors are caricatures of the
      normal process of tissue renewal with many stem cells and imperfect
      differentiation (14). This imparts an undifferentiated appearance to the tumors,
      not a dedifferentiated one. Study of the regulation of normal stem cells in the
      embryo should lead to rational therapies for malignant ones, and conversely,
      study of secretions and regulation of malignant stem cells will provide insights
      into normal regulation. The cancer-derived differentiated cells are benign (12,
      74) if not normal (39, 53) leading to the conclusion that attempts to direct
      normal differentiation of malignant stem cells might serve as an alternative to
      cytotoxic therapy. Attempts to develop such therapies are currently underway
      (208). The degree of differentiation of a carcinoma depends on the proportion of
      undifferentiated tumor stem cells, the stage of maturation arrest of the majority
      of cells in the tumor, and on the ability of some cells to escape arrest and to
      differentiate (Fig. 1). These concepts of the stem cell contribution to tumors
      originated largely from studies of teratocarcinoma (209) and were not widely
      accepted because many considered the lessons learned were unique to
      teratocarcinomas and would not apply to other tissues. On the basis of the
      concepts covered in this review, it is clear that teratocarcinomas are unique
      only in the potential of their stem cells. Other stem cells have more limited
      potential. The balance of expression of the differentiated histiotype of the
      tumor cell lineage and the undifferentiated phenotype of the tumor stem cells
      determine the morphology of the tumor. Normal tissue renewal of epithelial organs
      is also from stem cells or their differentiating progeny. The cellular events
      during liver development and regeneration and the changes that precede the
      development of liver cancer during hepatocarcinogenesis are similar to the
      cellular response in pancreas, prostate, breast, lung, and gut. In liver, as in
      the leukopoietic system, the primitive tissue-specific stem cell is not primarily
      involved in renewal because that would be too slow a process; individuals would
      die before generation of sufficient replacement cells.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8302020
TI  - Relationships between glycation and oxidation related fluorescences in rat
      collagen during aging. An in vivo and in vitro study.
AB  - BACKGROUND: Glycation and oxidation are spontaneous chemical modifications of
      body proteins. Usually these reactions have been studied separately by assessing
      their fluorescent final products. Glycation of protein and its related
      fluorescence increases during aging, whereas the level of the fluorescence
      related to protein adducts from lipoperoxidation side products is unknown.
      Moreover, no data on the fluorescence, at different wavelengths, connected to the
      two reactions in the same sample are available. Nevertheless recent in vitro
      studies support the possibility of an interaction between the two spontaneous
      reactions. EXPERIMENTAL DESIGN: In this study, we evaluated the modification of
      proteins due to glycation and to lipoperoxidation side products, by measuring
      their specific fluorescence levels in the collagen of 65 healthy Wistar rats
      during the aging process. The relationships among the fluorescence at different
      wavelengths were also reported. The fluorescence pattern of insoluble collagen
      was characterized by a tridimensional study after the incubation of insoluble
      collagen with probable precursors of protein glycation (ribose) and oxidation
      (malondialdehyde and hydroxynonenal); the maximum peaks of fluorescence were
      recognized and compared. RESULTS: An increase of all fluorescence intensities was
      observed in rat collagen during aging: the glycation-related ones (y370/440 =
      28.3 e0.08x, r = 0.808, p < 0.01; y335/385 = 66.7 e0.06x, r = 0.798, p < 0.01)
      and the hydroxynonenal adduct-related (y356/460 = 44.3 e0.06x, r = 0.810, p <
      0.01) were exponential, whereas that derived from MDA-adduct was almost linear
      (y390/460 = 17.7 + 4.1x, r = 0.661, p < 0.01). A different accumulation rate
      might explain this result. Significant correlation coefficients were found within
      the age-adjusted fluorescence intensities of both reactions, suggesting a close
      relationship between glycation and oxidation, besides a mutual influence due to
      the broad spectrum area. The in vitro study confirmed a good specificity of
      collagen fluorescence after incubation with a reducing sugar (ribose 0.5 M for 6
      hours) for protein glycation, and after incubation with malondialdehyde (0.1 mM
      for 3 hours) for lipoperoxidation adducts; surprisingly enough hydroxynonenal
      (0.5 mM for 3 hours) significantly increased the fluorescence related to
      pentosidine-like products (335 nm excitation/385 nm emission) suggesting that
      this compound might be the precursor of products with a fluorescence similar to
      pentosidine or of pentosidine itself. CONCLUSIONS: The in vivo results of this
      study confirm that nonenzymatic reactions, glycation and oxidation, significantly
      modify collagen fluorescence during aging and can play a role in tissue damage
      related to age. The close relationships among fluorescences may be due to a
      reciprocal interconnection rather than to a parallel increase of both reactions
      during aging; this hypothesis is supported by the in vitro findings of this
      study.

PMID- 8302021
TI  - Experimental IgA nephropathy secondary to hepatocellular injury induced by
      dietary deficiencies and heavy alcohol intake.
AB  - BACKGROUND: In humans, alcoholic liver disease is frequently associated with IgA
      mesangial deposits, microscopic hematuria and a small amount of proteinuria,
      identifying a secondary form of IgA nephropathy. Alcoholic liver disease is
      almost always associated with nutritional deficiencies. EXPERIMENTAL DESIGN: In
      order to examine the relationship between alcohol intake and/or inadequate diet
      and IgA nephropathy, groups of 4 week-old-male Lewis rats were maintained on a
      lipotrope-deficient (LD) diet (N = 20), intragastric infusions of a commercial
      whiskey (1.5 ml/100 gm body weight) three times a week, and regular chow (N = 23)
      or both intragastric whiskey infusion and an LD diet (N = 17). A fourth control
      group (N = 19) was given no whiskey and normal chow. RESULTS: All rats given the
      LD diet had marked steatosis and elevated "liver" enzymes. Changes were more
      severe, and with early bridging fibrosis and nodule formation in those also given
      whiskey, associated with increased hepatic content of mRNA encoding transforming
      growth factor-beta. A moderate steatosis without alteration in serum enzymes or
      transforming growth factor-beta expression was found in rats given whiskey (all p
      < 0.0001) compared with controls. IgA accumulated in hepatic sinusoids instead of
      in canaliculi and bile ducts, suggesting impaired transport of IgA and IgA immune
      complexes from blood to bile, in rats given an LD diet and/or whiskey infusion. A
      moderate increase in mesangial matrix was observed only in rats given both
      whiskey and an LD diet. Bright granular IgA and mild granular C3 mesangial
      deposits and electron-dense deposits were evident in 63 to 70% of experimental
      rats (all p < 0.001) versus only trace deposits in 5 to 11% of controls. Moderate
      IgG codeposits were present in 34 to 55% of rats given the LD diet and/or whiskey
      (all p < 0.02), versus trace deposits in 10% of controls. Significant hematuria
      and proteinuria were observed in rats given the LD diet and/or whiskey (p <
      0.0001) versus controls. Intestinal permeability measured by xylose absorption
      was significantly increased relative to controls only in rats given both whiskey
      and the LD diet (p < 0.001). Serum IgA specific for selected alimentary antigens
      was increased relative to controls in 75 to 100% of the experimental rats.
      CONCLUSIONS: The combination of LD diet and alcohol intake, which mimics the
      human alcoholic condition, promotes hepatic and renal changes, leading to
      hepatocellular injury and a secondary form of IgA nephropathy.

PMID- 8302022
TI  - Pathogenesis of cerebral infarction and hemorrhage induced by a murine leukemia
      virus.
AB  - BACKGROUND: Inoculation of neonatal BALB/c mice with the Friend murine leukemia
      virus TR1.3 uniformly induces cerebral infarctions and hemorrhages within 18
      days. The primary target of TR1.3 infection are endothelial cells of capillaries
      and small vessels. Preliminary post-mortem histologic analysis revealed
      multifocal endothelial cell pathology associated with the presence of thrombi and
      extravasation of red blood cells into the brain parenchyma. The consequences of
      viral infection on endothelial cell integrity and its relevance to hemorrhagic
      and ischemic lesions are unclear. EXPERIMENTAL DESIGN: Neonatal BALB/c mice were
      infected with TR1.3 murine leukemia virus and were monitored daily for symptoms
      of tremor, seizure and paralysis. Diseased mice were killed and the brains
      prepared for histopathologic analysis and electron microscopy studies. RESULTS:
      Hematoxylin and eosin-stained sections revealed widespread areas of infarction
      throughout white and grey matter with numerous scattered thrombi. Endothelial
      cell pathology was widespread and pronounced. This included enlarged cytoplasm,
      intracytoplasmic clefts, separation of tight junctions, swollen mitochondria,
      changes to the basal lamina and in many instances the formation of syncytia.
      Ultrastructural studies identified numerous viral particles within the
      endothelial cell cytoplasm and budding from the abluminal and luminal cell
      surfaces. CONCLUSIONS: These data confirm that TR1.3 virus replicates within
      endothelial cells and provides the first direct evidence of retrovirus-induced
      endothelial cell pathology. These results suggest that hemorrhage may be a direct
      consequence of this endothelial cell pathology, and that endothelial cell damage
      initiates the formation of thrombi and vessel occlusion that results in multiple
      cerebral infarctions.

PMID- 8302023
TI  - Developmental analysis of bone tumors in polyomavirus transgenic mice.
AB  - BACKGROUND: Transgenic mice carrying the polyoma (Py) early region gene develop
      both vascular and bone tumors that express the transgene (R. Wang and V. L.
      Bautch, J. Virol. 65:5174-5183, 1991). To determine the correlation between bone
      tumor formation and transgene expression, mice of two lines that showed
      differences in tumor pattern were analyzed. EXPERIMENTAL DESIGN: Py DNA encoding
      the early region gene was inserted into B6D2F1 mouse embryos. Transgenic mice
      were sacrificed at appropriate times in development, and the histopathology of
      the skulls and genotype analyses were performed independently. Py transgene
      expression was assayed in individual skulls or small groups of skulls. RESULTS:
      In mice of the Py-4 line, Py oncogene expression was detectable in skulls from
      14.5 days of development. These mice had normal skulls at birth, and they
      developed lesions histologically resembling osteosarcoma synchronously 1 to 2
      weeks after birth. Mice of the Py-3 line did not express detectable levels of
      transgene at 3 weeks of age, and they did not develop detectable skull pathology
      at this age. Less than 20% of adult Py-3 mice developed calvarial osteosarcoma
      like lesions, and a similar number of these mice expressed the transgene in the
      skull. CONCLUSIONS: These data show that Py transgene expression in bone of the
      skull is differentially regulated in mice of the two lines, and they indicate
      that epigenetic changes may be sufficient to complement expression of the Py
      oncogene in neoplastic bone formation during development.

PMID- 8302024
TI  - In vitro and in vivo growth of clonal sublines of human small cell lung carcinoma
      is modulated by polysialic acid of the neural cell adhesion molecule.
AB  - BACKGROUND: Polysialic acid (poly Sia) of the neural cell adhesion molecule (N
      CAM) is an oncodevelopmental antigen and is found in small cell lung carcinomas
      (SCLC) as well as cell lines derived from these tumors. EXPERIMENTAL DESIGN: Cell
      heterogeneity in poly Sia expression was observed in primary SCLC and cell
      cultures of SCLC by immunostaining using a directly gold-labeled monoclonal
      antibody against poly Sia (MAb 735) and antibodies against N-CAM. Clonal sublines
      of the N-CAM-positive SCLC cell line, NCI-H69 were established to study the basis
      of this heterogeneity. The resulting sublines were examined for the proportion of
      cells expressing poly Sia, the stability of poly Sia expression, and the possible
      involvement of DNA methylation. Two of the sublines that expressed poly Sia on 0
      and 95% of the cells were used in three independent in vitro assays to
      investigate the importance of poly Sia in cell-cell aggregation, disaggregation
      and cell to substrate adherence. Finally, clonogenic growth of these sublines was
      studied in soft agar and in the nude mouse. RESULTS: The proportion of cells
      immunoreactive for poly Sia was stable in serial subculture in these clones and
      was not affected by reducing DNA methylation. In aggregation and disaggregation
      assays, poly Sia was shown to modulate both calcium-dependent and independent
      cell-cell adhesion. No measurable differences in the attachment rates to various
      substrates (collagen type IV, laminin, heparan sulfate, and poly-L-lysine) were
      detected between the sublines. Cells from the poly Sia-positive clonal subline
      formed significantly more colonies in semisolid media and more intracutaneous
      metastasis in the nude mouse. CONCLUSIONS: Poly Sia does not occur on all N-CAM
      immunoreactive cells of SCLC. Poly Sia on SCLC cells is a clonable trait and high
      poly Sia expression correlates with reduced cell-cell adherence, a greater
      clonogenic ability in semisolid media, and a significantly higher incidence of
      intracutaneous metastases in nude mice.

PMID- 8302025
TI  - Remodeling of the constitutive equation while a blood vessel remodels itself
      under stress.
AB  - Changes in the mechanical properties of a blood vessel when it remodels itself
      under stress are reviewed. One of the recent findings about blood vessels is the
      rapidity of tissue remodeling when the blood pressure is changed. When the tissue
      structure and material composition remodel, the zero-stress state of the vessel
      changes. The mechanical properties change also in the remodeling process. If the
      elastic behavior is expressed in terms of a pseudo-elastic strain-energy
      function, then the constants in the function will change in the course of the
      remodeling. With all these changes taking place, the scope of constitutive
      equations broadens: it should now include a mass-and-structure growth-stress
      relationship as well as a stress-strain-relationship. To obtain the mass-and
      structure growth-stress relationship, one must be able to determine the
      mechanical properties of the different layers of the vessel wall, as well as the
      chemical composition and morphology. For the blood vessels, new methods of
      mechanical testing must be introduced. A key thought is to use bending of the
      blood vessel wall. By bending, different layers of the vessel wall are subjected
      to different stresses, leading to equations that can be used to solve the inverse
      problem of determining the stress-strain law from measured stress and strain. In
      vitro and in vivo experiments and theoretical prospectives are presented.

PMID- 8302026
TI  - Biomechanics of diarthrodial joints: a review of twenty years of progress.
AB  - A survey of some of the advances made over the past twenty years in understanding
      diarthrodial joint biomechanics is presented. Topics covered in this review
      include: biotribology (i.e., friction, lubrication and wear of diarthrodial
      joints); contact area determinations; stereophotogrammetric rendering of
      articular surfaces; deformational field analysis using canonical problems; and
      finite element formulations for both infinitesimal and finite deformations of
      biphasic materials and precise anatomic surfaces. Suggestions are made for future
      research directions as well.

PMID- 8302028
TI  - Constitutive modeling of articular cartilage and biomacromolecular solutions.

PMID- 8302027
TI  - Mathematical modeling of ligaments and tendons.
AB  - Ligaments and tendons serve a variety of important functions in maintaining the
      structure of the human body. Although abundant literature exists describing
      experimental investigations of these tissues, mathematical modeling of ligaments
      and tendons also contributes significantly to understanding their behavior. This
      paper presents a survey of developments in mathematical modeling of ligaments and
      tendons over the past 20 years. Mathematical descriptions of ligaments and
      tendons are identified as either elastic or viscoelastic, and are discussed in
      chronological order. Elastic models assume that ligaments and tendons do not
      display time dependent behavior and thus, they focus on describing the nonlinear
      aspects of their mechanical response. On the other hand, viscoelastic models
      incorporate time dependent effects into their mathematical description. In
      particular, two viscoelastic models are discussed in detail; quasi-linear
      viscoelasticity (QLV), which has been widely used in the past 20 years, and the
      recently proposed single integral finite strain (SIFS) model.

PMID- 8302029
TI  - Experimental approaches on measuring the mechanical properties and constitutive
      laws of arterial walls.
AB  - Studies on the elastic properties of arterial walls which have been done for the
      past two decades are surveyed briefly. After several in vitro and in vivo
      experimental methods and clinical techniques for the measurements of the
      mechanical behavior of arterial walls have been reviewed, data obtained of the
      basic characteristics of the arterial wall, including wall incompressibility and
      anisotropy, are discussed. The author then reviews constitutive laws proposed for
      the description of stress-strain relationships of arterial walls and methods for
      the parametric expression of pressure-diameter data, and shows data on the
      effects of aging and vascular diseases on arterial mechanics. Finally, residual
      stress in the arterial wall is discussed.

PMID- 8302030
TI  - Finite element models for arterial wall mechanics.
AB  - Arterial wall mechanics has been studied for nearly 200 years. This subject is of
      importance if we are to gain a fundamental understanding of this complex
      biological structure, as well as information needed to design prosthetics.
      Biomechanical arterial models continue to play an important role in the study of
      atherosclerosis, a disease of the arterial wall that is the chief cause of
      mortality and morbidity in the United States and the Western World. Over the past
      20 years, the finite element model (FEM) has been used in a variety of ways to
      simulate the structural response of large arteries. Our purpose is to summarize
      the uses of FEMs in arterial mechanics. We will also indicate directions for
      future research in this area. A specialized FEM was described in the literature
      for the study of transport in the arterial wall, however the convection was not
      directly linked to arterial wall mechanics. In this paper special attention will
      be given to the development of FEMs based on the poroelastic view of arterial
      tissues which couple wall deformation, free tissue fluid motion, and associated
      transport phenomena in the arterial wall. In the future such models should
      provide fundamental quantitative information relating arterial wall mechanics and
      transport which may lead to a better understanding of both normal arterial
      physiology and atherogenesis.

PMID- 8302031
TI  - Nonhomogeneous ventricular wall strain: analysis of errors and accuracy.
AB  - Nonhomogeneous distributions of strains are simulated and utilized to determine
      two potential errors in the measurement of cardiac strains. First, the error
      associated with the use of single-plane imaging of myocardial markers is
      examined. We found that this error ranges from small to large values depending on
      the assumed variation in stretch. If variations in stretch are not accompanied by
      substantial regional changes in ventricular radius, the associated error tends to
      be quite small. However, if the nonuniform stretch field is a result of
      substantial variations in local curvature from their reference values, large
      errors in stretch and strain occur. For canine hearts with circumferential radii
      of 2 to 4 cm, these errors in stretch may be as great as 30 percent or more.
      Moreover, gradients in stretch may be over- or underestimated by as much as 100
      percent. In the second part of this analysis, the influence of random measurement
      errors in the coordinate positions of markers on strains computed from them is
      studied. Arrays of markers covering about 16 cm2 of ventricular epicardium are
      assumed and nonuniform stretches imposed. The reference and deformed positions of
      the markers are perturbed with Gaussian noise with a standard deviation of 0.1
      mm, and then strains are computed using either homogeneous strain theory or a
      nonhomogeneous finite element method. For the strain distributions prescribed, it
      is found that the finite element method reduces the error resulting from noise by
      about 50 percent over most of the region. Accurate measurements of cardiac strain
      distributions are needed for correlation with and validation of realistic three
      dimensional stress analyses of the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302032
TI  - Active motion of polymorphonuclear leukocytes in response to chemoattractant in a
      micropipette.
AB  - A novel experimental method of producing and observing the active motion of
      polymorphonuclear leukocytes (PMNs) using a micropipette technique has been
      recently developed (Usami et al., 1992). The present paper develops a
      quantitative theory for the chemoattractant gradients and cell locomotion
      observed in these experiments. In previous experimental methods (e.g., the Boyden
      chamber, the Zygmond chamber and the Dunn chamber) for study chemotaxis of
      leukocytes, fibroblasts, and PMNs, the exact nature of the concentration gradient
      of the chemoattractant is unknown. The cells may themselves modify the local
      gradient of the chemoattractant. In experiments using the micropipette, an
      internal source of chemoattractant provides well-defined boundary and initial
      conditions which allow the computation of the chemoattractant concentration
      gradient during the active locomotion of the PMNs. Since the cell completely
      fills the pipette lumen, convection is limited to the motion of the cells
      themselves. In coordinates moving with cell, it is assumed that diffusion is the
      only mechanism of mass transport of the chemoattractant (fMLP). Computations of
      the fMLP concentration during locomotion of the cell were carried out for a range
      of rates of fMLP binding by the receptors expressed on the front face of the cell
      membrane. The results show that the front face of the cell is subjected to
      increasing fMLP concentration during the cell motion. The sequence of events
      involve receptor binding of fMLP, signal transduction, polymerization of the cell
      cytoskeleton at the membrane of the front face, spatially dependent adhesion to
      the pipette wall, and localized contraction of the cytoskeleton. This sequence of
      events leads to the steady locomotion of the leukocytes in the micropipette. The
      computation of the distribution of the fMLP concentration during cell locomotion
      with constant velocity in micropipette experiments shows that the cell is exposed
      to increasing concentration of fMLP. This suggests that chemotaxis maybe induced
      by temporal gradient of an attractant.

PMID- 8302033
TI  - Hemodynamics and the vascular endothelium.
AB  - The endothelium, once thought to be a passive, non-thrombogenic barrier, is now
      recognized as being a dynamic participant in vascular biology and pathobiology.
      Part of its dynamic nature is due to the influence of the mechanical environment
      imposed by the hemodynamics of the vascular system. Over the past two decades
      much has been learned about the influence of hemodynamics on the vascular
      endothelium. This has been in part through in vivo experiments; however, in the
      past 15 years a number of laboratories have turned to the application of in vitro
      cell culture systems to investigate the influence of flow and cyclic stretch on
      the biology of vascular endothelium. Taken together these studies demonstrate
      that flow and the associated shear stress modulate both endothelial cell
      structure and function. Cell culture studies employing cyclic stretch provide
      similar evidence. Furthermore, these effects of mechanical environment extend to
      the gene expression level, with there being a differential regulation of mRNA. A
      critical question is how does an endothelial cell recognize the mechanical
      environment in which it resides and, having done so, how is this transduced into
      the changes in structure and function observed? Although our knowledge of the
      recognition events remains limited, studies on signal transduction in response to
      a mechanical stimulus indicate that many of the second messengers known to be
      triggered by chemical agonists also are involved in transducing a mechanical
      signal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302034
TI  - Measuring the mechanical properties of individual human blood cells.
AB  - The largest human blood cells--the red cells (erythrocytes) and white cells
      (leukocytes)--must undergo a significant amount of deformation as they squeeze
      through the smallest vessels of the circulation and the small openings between
      bone, vessel and tissue. This ability to deform in response to external forces
      shows that cells exhibit material behavior and behave as either elastic solids or
      viscous liquids. The question then is "how can we measure the deformation and
      flow of something as small as a blood cell and what kinds of constitutive
      equations describe cellular deformation"? In this paper the use of the micropipet
      to measure red cell and white cell, especially neutrophil, deformation will be
      described and the viscoelastic models used to describe the deformation behavior
      of red cell membrane and neutrophil cytoplasm will be discussed. Values for the
      elasticities of a red cell membrane subjected to shear, area expansion and
      bending will be given. The viscosity of red cell membrane in shear will also be
      discussed. Finally, the cortical tension of the neutrophil and the Newtonian and
      Maxwell models used to characterize its apparent viscosity will be discussed even
      though neither is wholly successful in describing the viscous behavior of the
      neutrophil. Thus, alternate models will be suggested.

PMID- 8302035
TI  - From structure to process, from organ to cell: recent developments of FE-analysis
      in orthopaedic biomechanics.
AB  - The introduction of finite element analysis (FEA) into orthopaedic biomechanics
      allowed continuum structural analysis of bone and bone-implant composites of
      complicated shapes (Huiskes and Chao, J. Biomechanics, Vol. 16, 1983, pp. 385
      409). However, besides having complicated shapes, musculoskeletal tissues are
      hierarchical composites with multiple structural levels that adapt to their
      mechanical environment. Mechanical adaptation influences the success of many
      orthopaedic treatments, especially total joint replacements. Recent advances in
      FEA applications have begun to address questions concerning the optimality of
      bone structure, the processes of bone remodeling, the mechanics of soft hydrated
      tissues, and the mechanics of tissues down to the microstructural and cell
      levels. Advances in each of these areas, which have brought FEA from a continuum
      stress analysis tool to a tool which plays an ever-increasing role in the
      scientific understanding of tissue structure, adaptation, and the optimal design
      of orthopaedic implants, are reviewed.

PMID- 8302037
TI  - A 20-year perspective on the mechanical properties of trabecular bone.
AB  - We have reviewed highlights of the research in trabecular bone biomechanics
      performed over the past 20 years. Results from numerous studies have shown that
      trabecular bone is an extremely heterogeneous material--modulus can vary 100-fold
      even within the same metaphysis--with varying degrees of anisotropy. Strictly
      speaking, descriptions of the mechanical properties of trabecular bone should
      therefore be accompanied by specification of factors such as anatomic site,
      loading direction, and age. Research efforts have also been focused on the
      measurement of mechanical properties for individual trabeculae, improvement of
      methods for mechanical testing at the continuum level, quantification of the
      three-dimensional architecture of trabecular bone, and formulation of equations
      to relate the microstructural and continuum-level mechanical properties. As
      analysis techniques become more sophisticated, there is now evidence that factors
      such as anisotropy and heterogeneity of individual trabeculae might also have a
      significant effect on the continuum-level properties, suggesting new directions
      for future research. Other areas requiring further research are the time
      dependent and multiaxial failure properties at the continuum level, and the
      stiffness and failure properties at the lamellar level. Continued research in
      these areas should enhance our understanding of issues such as age-related bone
      fracture, prosthesis loosening, and bone remodeling.

PMID- 8302036
TI  - Bone stress adaptation models.
AB  - The basic concepts employed in formulating models of the process of stress
      adaptation in living bone tissue are reviewed. A purpose of this review is to
      define and separate issues in the formulation of bone remodeling theories. After
      discussing the rationale and objective of these models, the concepts and
      techniques involved in the modeling process are reviewed one by one. It is
      concluded that some techniques will be more successful than others in achieving
      the goals of computational bone remodeling. In particular, rationale is given for
      the preference of surface bone remodeling approaches over internal bone
      remodeling approaches, and for interactive multi-scale level, rather than mono
      scale level, computational strategies.

PMID- 8302038
TI  - Scanning acoustic microscope studies of the elastic properties of osteons and
      osteon lamellae.
AB  - Scanning acoustic microscopy (SAM) provides the means for studying the elastic
      properties of a material at a comparable level of resolution to that obtained by
      optical microscopy for structural studies. SAM is nondestructive and permits
      observation of properties in the interior of materials which are optically
      opaque. Two modes of ultrasonic signals have been used in a Model UH3 Scanning
      Acoustic Microscope (Olympus Co., Tokyo, Japan) as part of a continuing study of
      the microstructural properties of bone. The pulse mode, using a single narrow
      pulse in the range of 30 MHz to 100 MHz, has been used to survey the surface and
      interior of specimens of human and canine femoral compact cortical bone at
      resolutions down to approximately 30 microns. To obtain more detailed information
      at significantly higher resolution, the burst mode, comprised of tens of
      sinusoids, has been used at frequencies from 200 MHz to 600 MHz. This has
      provided details of both human and canine single osteons (or haversion systems)
      and ostenoic lamellae at resolutions down to approximately 1.7 microns, well
      within the thickness of a lamella as viewed in a specimen cut transverse to the
      femoral axis.

PMID- 8302039
TI  - Fracture mechanics of bone.
AB  - This paper reviews the progress that has been made in applying the principles of
      fracture mechanics to the topic of fracture of long bones. Prediction of loading
      conditions which result in the propagation of fractures in bones has been of
      interest to the field of trauma biomechanics and orthopedics for over one hundred
      years. Independent verifications, by various investigators, of bone fracture
      mechanics parameters are reviewed and investigations of the effects of bone
      density and specimen thickness on the critical fracture mechanics parameters and
      of other factors such as critical crack length and plastic zone size in bovine
      femoral bone, and the effects of crack velocity on fracture mechanics parameters
      in bovine tibial bone are discussed. It took over ten years for the techniques of
      bone fracture mechanics to be applied to human compact bone, due primarily to
      geometric constraints from the smaller size of human bones. That work will be
      reviewed along with other continuing work to define the orientation dependence of
      the fracture mechanics parameters in bone and to refine the experimental
      techniques needed to overcome the geometric constraints of specimen size. A
      discussion is included of work still needed to determine fracture mechanics
      parameters for transverse and longitudinal crack propagation in human bone and to
      establish the effects of age on those parameters. Finally, a discussion will be
      given of how this knowledge needs to be extended to allow prediction of whole
      bone fracture from external loading to aid in the design of protective systems.

PMID- 8302040
TI  - The artificial heart: history and current status.
AB  - Twenty-years ago groups from California to Massachusetts were actively involved
      in the development of an artificial heart. From biomaterials development to
      biomedical power sources, the supporting industry and spin-off benefit was broad
      indeed. Young people were seeking careers in biomedical engineering and science.
      The National Institutes of Health was supporting artificial heart research at $10
      to $12 million dollar levels. Groups at Andros, Inc. (now Baxter Novacor) and
      Stanford, Thoratec, Penn State and the Hershey Medical Center, Cleveland Clinic
      and the Division of Artificial Organs, the University of Utah, the Texas Heart
      Institute and the Baylor College of Medicine, Thermal Electron Corporation, and
      many more were the source of research and breakthrough development of pumps and
      systems for artificial hearts. We reported on performance criteria for an
      artificial heart pump at the First Biomechanics Symposium in 1973 [1]. By the
      beginning of the decade of the 90's, thousands of presentations had been made and
      manuscripts written reporting significant progress in the development of
      artificial heart pumps and systems. The Heart, Lung and Blood Institute of the
      National Institutes of Health was supporting an artificial heart contract
      research and development program at a level of $6 million dollars in 1991 [2].
      Broad basic research grant activity also continues. The National Institutes of
      Health's artificial heart program received renewed support from the Institute of
      Medicine's special review in 1991 [3]. In December of 1992, the 16th Annual
      Cardiovascular Science and Technology Conference attracted over 500 attendees.
      This annual conference has provided a continuing forum for an update on progress
      in artificial heart development.

PMID- 8302041
TI  - The coronary circulation.
AB  - Dramatic advances have been made in the last two decades in the diagnosis and
      treatment of coronary artery disease. The development of open heart surgical
      techniques for bypassing occluded arteries made quantitative diagnostic
      techniques more important. Computer enhanced angiographic methods, together with
      measurements using tomography, ultrasound and magnetic resonance imaging have
      greatly improved the precision of the diagnosis. A more complete understanding of
      coronary mechanics and control has enabled physicians to better interpret the
      significance of geometric information and to supplement this information with
      functional assessment of stenosed arteries. Finally, traditional bypass surgery
      is now supplemented with closed-chest techniques such as balloon angioplasty.
      Biomedical engineers have been involved in all of these developments. This paper
      will review these developments and attempt to identify remaining questions.

PMID- 8302042
TI  - Simulation and animation of musculoskeletal joint system.
AB  - This paper describes the development of computer-based software for three
      dimensional geometric data base of the human musculoskeletal system. Using a
      computer graphics workstation, a user of the software will interactively display
      detailed information about the muscles, tendons, ligaments, bone, and joint
      anatomy. This software will enable a wide range of health care workers to
      visualize complex physiological data. In addition to geometric and visual
      realism, this software will include kinematic relationships which allow the
      calculation and display of the motion and forces of the joints, muscles, and
      tendons. This will permit a user to interactively move joints or tendons and
      display the resulting motion of the surrounding tissues, as well as internal
      reactive forces and joint pressure distribution. A two-dimensional version of
      this software is currently being used for knee and hip osteotomy preoperative
      planning, total joint replacement prosthesis design and dimensional selection,
      and osteochondral allograft sizing and reconstruction using radiographic data.

PMID- 8302043
TI  - Spinal biomechanics.
AB  - The lumbar spine is a source of disability due to low back pain (LBP), yet the
      precise diagnosis is unknown in 80-90 percent of patients. The lifetime
      prevalence is 75 percent with a cost to the U.S. economy as high as 80 billion
      dollars. The problem is partly caused by mechanical overloading of the tissues
      and thus, there is some potential for both primary and secondary prevention.
      Biomechanical techniques have been effective in improving our understanding of
      the loading conditions leading to LBP, and in developing techniques for improved
      diagnosis and more effectual methods of treatment. Much progress has been made
      through the use of biomechanical models. Most models assume that the external
      moments are balanced by trunk musculature. Multiple muscle system models,
      employing agonist and antagonists, now are available to define 3D spine reaction
      forces. The static indeterminacy is taken care of either by simplification of the
      model or by linear or nonlinear optimization. Dynamic analysis has shown that
      vibrational and impact conditions (such as vehicle driving) can excite the
      natural frequency of the spine and lead to high spinal loadings. In vivo
      measurements have shown the resonant frequency of the lumbar spine to be 4-5 Hz
      and many vehicles excite those frequencies. New biomechanical techniques
      employing electromyography can estimate muscle load and muscle fatigue. Stereo
      photogrammetric techniques for establishing segmental kinematics have great
      potential for improving the diagnosis of spinal problems. These techniques are
      solidly based on prior in-vitro measurements of spinal kinematics. Mechanical
      fixation techniques, such as pedicle fixation, show great promise in improving
      the treatment of spinal problems. These have been extensively analyzed by both
      finite element techniques and in-vitro simulation so as to improve design as well
      as surgical technique.

PMID- 8302044
TI  - Functional analysis of pre and post-knee surgery: total knee arthroplasty and ACL
      reconstruction.
AB  - This paper examines the biomechanics of total knee arthroplasty as a treatment
      for arthritis and anterior cruciate ligament (ACL) reconstruction for repair of
      torn anterior cruciate ligaments of the knee. These are two of the most frequent
      reconstructive procedures for the knee joint. Functional testing of patients
      while performing various activities of daily living was used to study the
      relationship between the intrinsic biomechanics of the knee and function. The
      results of the study of patients following total knee replacement demonstrated a
      dynamic interaction between the posterior cruciate ligament and quadriceps
      function during stairclimbing. The study of patients with ACL-deficient knees
      demonstrated that loss of the anterior cruciate ligament can cause the avoidance
      of quadriceps contraction during activities when the knee is near full extension.
      Other studies demonstrated a relationship between tibiofemoral joint mechanics
      and patellofemoral mechanics. In addition, the importance of combined ligamentous
      laxity with higher than normal adduction moments during gait was examined in
      relationship to progressive degenerative changes to the medial compartment of the
      knee. In summary, functional testing such as gait analysis has proven to be an
      important basic research tool as well as extremely effective for clinical testing
      of new procedures and devices.

PMID- 8302045
TI  - Progress of research on impact biomechanics.
AB  - Impact biomechanics is an area of research primarily associated with the
      protection of vehicular occupants. It is also concerned with the prevention of
      sports-related injuries and with injuries due to falls. It deals mainly with
      loads that have high rates of onset and with durations that are considerably less
      than one second. The objectives of impact biomechanics are to understand how a
      body region is injured in an impact and to seek means to minimize injury through
      environmental modifications. A secondary objective is to ensure that such
      environmental modifications do not become a secondary source of injury. Impact
      biomechanics can be broadly categorized into four areas. They are Mechanisms of
      Injury, Human Response to Impact, Human Tolerance to Impact, and Development of
      Human Surrogates for Impact Simulation. Each area plays a role in the design of
      automotive restraint systems and interior structures and in the understanding of
      how injury is caused so that effective countermeasures can be taken to minimize
      the injury. This paper describes advances made in all four areas of impact
      biomechanics over the last two decades. Areas of current research interest are
      also discussed. They point to the need for new data and further research work in
      impact biomechanics.

PMID- 8302046
TI  - The role of fluid mechanics in the localization and detection of atherosclerosis.
AB  - Fluid dynamics research over the past twenty years has contributed immensely to
      our knowledge of atherosclerosis. The ability to detect localized atherosclerotic
      plaques using noninvasive ultrasonic methods was advanced significantly by
      investigations into the nature and occurrence of velocity disturbances created by
      arterial stenoses, and diagnosis of carotid bifurcation disease using a
      combination of ultrasonic imaging and Doppler measurement of blood velocity is
      now quite routine. Since atherosclerotic plaques tend to be localized at sites of
      branching and artery curvature and since these locations would be expected to
      harbor complex flow patterns, investigators postulated that fluid dynamics might
      play an initiating role in atherogenesis. Several fluid dynamic variables were
      proposed as initiating factors. Investigations were undertaken during the 1980s
      in which fluid dynamic model experiments with physiologic geometries and flow
      conditions were employed to simulate arterial flows and in which morphometric
      mapping of intimal thickness was performed in human arteries. Correlations
      between fluid dynamic variables and intimal thickness revealed that
      atherosclerotic plaques tended to occur at sites of low and oscillating wall
      shear stress; and these observations were reinforced by studies in a monkey model
      of atherosclerosis. Concomitantly, it was realized that arteries adapt their
      diameters so as to maintain wall shear stress in a narrow range of values around
      15 dynes/cm2, findings which were based both on observations of normal arteries
      and on animal studies in which flow rates were manipulated and arterial diameter
      adaptation was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302047
TI  - Arteriosclerosis research using vascular flow models: from 2-D branches to
      compliant replicas.
AB  - A large body of evidence implicates fluid dynamic forces in the genesis and
      progression of atherosclerosis, the leading cause of death in the United States.
      To understand the mechanism by which hemodynamics influences the disease process,
      and to identify the specific flow variable(s) responsible for its localization,
      it is essential to know the distribution of hemodynamic variables in susceptible
      regions of the vasculature. Vascular flow models have been used more than any
      other means to gain insight into the details of arterial hemodynamics. The first
      flow models were not very realistic. Our first attempt, reported at an early
      Biomechanics Symposium, was probably the most unrealistic of all: a "2-D branch"
      that was constructed to validate a 2-D computed flow field. Most of the first
      models were made of cylindrical tubes, and their geometry too only approximated
      that of real arteries. Much was learned about the fluid dynamics in branches and
      bends using such models, but measurements in them could be related only generally
      to the fluid dynamics in living vessels. Accordingly, we began to make flow field
      measurements in replicas prepared from human arteries. Others challenged their
      glassblowers and shops to make models more representative of real vessels. These
      flow-through casts and fabricated models were initially rigid and perfused with
      Newtonian fluids. Using these more realistic systems, we and others were able to
      demonstrate relationships between specific hemodynamic variables and localized
      arterial pathology. The fidelity of flow simulations today exceeds that of only a
      few years ago. We now perfuse compliant replicas as small as coronary diagonal
      branches with fluids whose rheology mimics blood.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8302048
TI  - Lipid transport aspects of atherogenesis.
AB  - In this review we shall examine the current understanding of events that lead to
      the incipient formation of the early foam cell lesion in atherogenesis and its
      localization. Particular emphasis will be placed on the intimal transport
      mechanisms that lead to the growth of extracellular lipid liposomes in the
      intima, since there is now substantial evidence that this growth is the
      triggering event in the complex sequence of processes that leads to the
      recruitment of blood borne monocytes into the subendothelial intima and their
      subsequent conversion to macrophages. The role of the endothelium, intimal
      proteoglycans and internal elastic lamina (IEL) in modulating the transport of
      low density lipoproteins (LDL) in the subendothelial space will be analyzed and a
      new hypothesis for the co-localization of liposome formation, cellular level
      endothelial leakage and monocyte entry described. The possible modifications of
      LDL in the liposomes that facilitate the conversion of monocytes into foam cells
      is summarized. We also discuss the fluid dynamic aspects of intimal transport and
      the relationship of fluid shear stress to the localization of cellular level
      endothelial leakage of LDL. The effect of fluid shear on other endothelial cell
      functions has been recently reviewed in [1].

PMID- 8302049
TI  - Flow dynamics in the human aorta.
AB  - The aorta is the major blood vessel transporting blood pumped by the left
      ventricle to the systemic circulation. The tricuspid aortic value at the root of
      the aorta provides a centralized flow with nearly uniform velocity profile into
      the ascending aorta. The aorta consisting of the ascending limb, the aortic arch,
      and the descending segment is a vessel of complex geometry including curvature in
      multiple planes, branches and bifurcation as well as taper. The understanding of
      the development of blood flow in this distensible vessel has been the subject of
      several theoretical as well as experimental investigations. Flow development in
      the aorta and in the branch vessels has been of interest in delineating the role
      of wall shear stresses on the etiology of atherosclerosis. In this paper, a
      review of the current status on our understanding of the complex flow dynamics in
      the aorta is presented. With the advent of transesophageal echocardiography and
      magnetic resonance velocity mapping, further evidence of the presence of
      secondary flows even in the descending aorta has been reported. The importance of
      the effect of secondary flow in the descending aorta on the perfusion of distal
      blood vessels (such as superior mesenteric and renal arterial branches) as well
      as in the iliac bifurcation is also included in the discussion.

PMID- 8302050
TI  - Thermal (heat) shock biothermomechanical viewpoint.
AB  - Thermal (or heat) shock phenomena have been observed in all organisms at the
      cellular level. They cause an acceleration in the rate of expression of specific
      genes (heat shock genes), resulting in an increase and accumulation of heat shock
      proteins in cells. The purpose of this study is to investigate the mechanisms of
      thermal shock from two different viewpoints: biothermal and biothermomechanical
      aspects. The former predicts more severe consequences on cells that the latter,
      whose thermal wave fronts are smoothed due to the coupling effects of
      thermoelasticity. In conclusion, it is the thermal wave propagation (the so
      called "second sound" effect) which triggers a perturbation of normal gene
      expression. Thermotolerance is found to be inherited in the heat flux equation of
      the thermal wave model. The information obtained from this study can also be
      useful to therapeutical hyperthermia, preservation of organs and tissues, and
      laser and cryogenic surgery.

PMID- 8302051
TI  - If I were king.

PMID- 8302052
TI  - Result of biventricular repair for double-outlet right ventricle.
AB  - The choice of optimal repair for many patients with double-outlet right ventricle
      continues to challenge the heart surgeon. We present the results of a 10-year
      surgical experience with the biventricular repair for double-outlet right
      ventricle with situs solitus and atrioventricular concordance. Preoperative
      anatomic findings within this population of 73 patients are detailed. These
      morphologic features are correlated with type of anatomic repair and clinical
      outcome. Patients were classified by ventricular septal defect location. Normal
      coronary anatomy was found in the majority of patients with subaortic and doubly
      committed ventricular septal defects. Patients with subpulmonary and noncommitted
      ventricular septal defects had a wide variety of coronary anatomy. Patients with
      subpulmonary and noncommitted ventricular septal defects also had a considerably
      higher prevalence of aortic arch obstruction. A tricuspid-to-pulmonary annular
      distance equal to or greater than the diameter of the aortic annulus was found to
      indicate the possibility of achieving a conventional ventricular septal defect-to
      aorta intraventricular tunnel repair. Tricuspid-to-pulmonary annular distance
      sufficient for intraventricular tunnel repair predominates in those patients with
      a right posterior or right side-by-side aorta. Five types of repair were used
      during the study period: intraventricular tunnel repair, arterial switch with
      ventricular septal defect-to-pulmonary artery baffle, Rastelli-type extracardiac
      conduit repair, Damus-Kaye-Stansel repair, and atrial inversion with ventricular
      septal defect-to-pulmonary artery baffle. Overall actuarial survival estimate at
      8 years is 81%. The presence of multiple ventricular septal defects and patient
      weight lower than the median were nearly significant risk factors for early
      mortality (p < 0.06). Nineteen patients (26%) required 24 reoperations. Patients
      with subaortic ventricular septal defects were significantly reoperation free (p
      < 0.05). Patients with noncommitted ventricular septal defects were at
      significantly higher risk for reoperation during the study period (p < 0.05). The
      prevalence of late right or left ventricular outflow obstruction in the
      nonsubaortic groups is concerning. The median age at repair in this series was
      0.76 years, and there was a nonsignificant trend (p = 0.13) for early mortality
      in patients younger than 1 year of age. These patients tended to have other
      serious cardiac anomalies associated with double-outlet right ventricle that
      necessitated early operation. On the basis of these data, we favor early repair
      for double-outlet right ventricle if possible.

PMID- 8302053
TI  - Double switch operation in cardiac anomalies with atrioventricular and
      ventriculoarterial discordance.
AB  - Since June 1987, 10 of 19 consecutive patients with atrioventricular and
      ventriculoarterial discordance (average age 4 +/- 2 years) had undergone a double
      switch operation with the morphologically left ventricle used as a systemic
      ventricle. There were two combinations of procedures. Atrial switch combined with
      arterial switch was used in two patients who had a normal pulmonary valve. Atrial
      switch combined with ventriculoarterial switch by Rastelli's procedure was used
      in eight patients with pulmonary stenosis or atresia and a large ventricular
      septal defect. One early death and two late deaths have occurred in a
      postoperative follow-up period of up to 4 years. Subsequent problems were mainly
      related to the results of atrial switch procedures in patients who had a small
      atrium because of low pulmonary flow, especially in patients with apicocaval
      juxtaposition. Our experience suggested that the double switch operation would
      open a new era of definitive surgical treatment in half of the patients with
      atrioventricular and ventriculoarterial discordance.

PMID- 8302054
TI  - Outcome measures for the neonatal management of pulmonary atresia with intact
      ventricular septum.
AB  - The outcome in 135 patients with pulmonary atresia with intact ventricular septum
      was reviewed in terms of actuarial survival and "suitability" for eventual
      definitive repair (defined as having a tricuspid valve diameter larger than 2.4
      standard deviations below the mean normal beyond the neonatal period). Of
      patients who underwent an initial closed valvotomy, 50% were dead, 22% were alive
      and suitable, and the remaining 28% were alive but unsuitable for definitive
      repair at 5 years. None of 66 patients who underwent primary shunt alone achieved
      suitability and 52% were dead at 5 years. No mode of neonatal closed valvotomy
      was consistently satisfactory: in only 10 of 26 survivors with serial
      measurements did the neonatal valvotomy alone achieve decompression to
      subsystemic pressures. Only half of the decompressed ventricles achieved growth
      of the tricuspid valve disproportionate to somatic growth as a result of the
      neonatal procedure. Strategies for the neonatal treatment of pulmonary atresia
      with intact ventricular septum should not rely on closed operations on the
      pulmonary valve to optimized right ventricular growth.

PMID- 8302055
TI  - Aortic root replacement with pulmonary autograft in children.
AB  - Between September 1988 and February 1993, 14 patients whose ages ranged from 3
      months to 16 years (mean 11.1 +/- 4.3 years) underwent replacement of the aortic
      root with the autologous pulmonary root for aortic valve disease. The follow-up
      was 4 years (cumulative total of 25.2 patient-years). There was no early
      mortality. Late mortality (one patient) was 7.1% (95% confidence limits 0% to
      21%). This patient had juvenile rheumatoid arthritis and died of consequent
      congestive heart failure with autograft failure 6 months after operation. Event
      free survival after 4 years was 78.6% (95% confidence limits 50% to 95%). One
      patient was reoperated on because of autograft failure caused by a relapse of
      rheumatic fever. One patient operated on for critical neonatal aortic stenosis
      has subnormal exercise tolerance because of restrictive cardiomyopathy and
      pulmonary homograft regurgitation. The other 12 patients were in New York Heart
      Association functional class I at the end of follow-up. There was no prevalence
      of bacterial endocarditis. There were no signs of primary structural degeneration
      of the pulmonary autograft. During follow-up, in eight patients, increased anulus
      diameter of the pulmonary autograft could be demonstrated by precordial two
      dimensional echocardiography, suggesting growth of the autograft. Our experience
      shows that aortic root replacement with the pulmonary autograft can be done with
      low mortality and morbidity in children with aortic valve disease. The operation
      seems to be contraindicated in children with juvenile rheumatoid arthritis
      because of the risk of recurrence of rheumatic disease in the autograft. The
      pulmonary autograft has also been shown to be susceptible to recurrence of
      rheumatic inflammation in children with a history of acute rheumatic fever.
      Despite pulmonary autograft replacement of the aortic valve in infants with
      critical valvular aortic stenosis and endocardial fibroelastosis, clinical
      results may be poor. Growth of the autograft is suggested by echocardiographic
      follow-up. We consider aortic root replacement with the pulmonary autograft the
      procedure of choice in children who require aortic valve replacement.

PMID- 8302056
TI  - Energy expenditure in children with congenital heart disease, before and after
      cardiac surgery.
AB  - Failure to thrive is a common feature of children with congenital heart disease.
      Whether this is the result of poor nutrition or an abnormally high basal
      metabolic rate is unknown, yet the state of nutrition has a profound effect on
      the metabolic response to injury and strongly influences the outcome of surgical
      treatment. The aim of this study was therefore to measure the preoperative and
      postoperative energy requirements of children with congenital heart disease.
      Eighteen children (aged 4 to 33 months) were given two oral doses of doubly
      labeled water (H2(18)O and 2H2O), the first 1 week before operation and the
      second 6 hours after the end of cardiac surgery. By measuring the relative loss
      of each isotope from the body water pool, we were able to calculate the rate of
      carbon dioxide production and therefore total energy expenditure. In five
      patients, energy expenditure was clearly elevated, suggesting that a raised basal
      metabolic rate is an important factor in the observed failure to thrive in at
      least a proportion of such children. Postoperatively, energy expenditure fell to
      values below normal for healthy children (not having an operation), which
      suggests that the stress of surgery leads to smaller energy requirements than
      have previously been thought.

PMID- 8302057
TI  - Determinants of reoperation after 960 valve replacements with Carpentier-Edwards
      prostheses.
AB  - During the period of 1977 to 1990, 960 Carpentier-Edwards standard prostheses
      (Baxter Healthcare Corp., Santa Ana, Calif.) were placed in 875 operations.
      Freedom from reoperation at 10 years was 57% +/- 4%, 76% +/- 3%, and 95% +/- 5%
      for mitral, aortic, and tricuspid valve replacement, respectively. Age was the
      only independent determinant of reoperation for both aortic and mitral valves.
      Likelihood of reoperation decreased with age, with freedom from reoperation after
      10 years in patients aged less than 60 years versus 60 or more years being 65% +/
      5% versus 90% +/- 4% after aortic valve replacement and 48% +/- 5% versus 75% +/
      6% after mitral valve replacement. For mitral valve replacement, larger valve
      size made reoperation more likely, with freedom from reoperation at 10 years
      being 71% +/- 6% for sizes median less than 31 mm and 57% +/- 5% for sizes 31 mm
      or larger. For aortic valve replacement, prior median sternotomy reduced freedom
      from reoperation at 10 years from 80% +/- 3% to 25% +/- 5%. The low prevalence of
      reoperation affirms the suitability of the Carpentier-Edwards prosthesis for
      selected elderly patients and for tricuspid valve replacement. Because of their
      influence on the probability of reoperation, valve size and prior cardiac
      procedures also merit consideration in the choice of valvular prosthesis.

PMID- 8302058
TI  - Early and late-phase events after valve replacement with the St. Jude Medical
      prosthesis in 1200 patients.
AB  - From May 1982 to August 1991, 1200 patients underwent valve replacement with the
      St. Jude Medical (St. Jude Medical, Inc., St. Paul, Minn.) valve: 615 men (51%)
      and 585 women, mean age 58 years. Preoperatively, 830 patients (69%) were in
      functional class III or IV. A total of 611 patients (51%) had the aortic valve
      replaced, 490 (41%) the mitral valve, 2 (0.2%) the tricuspid valve, and 97 (8%)
      multiple valves. There were 81 hospital deaths (6.8%). Risk factors included
      older age (p = 0.0001), female gender (p = 0.02), higher preoperative left
      ventricular end-diastolic pressure (p = 0.05), previous cardiac operation (p =
      0.003), longer aortic crossclamp time (p = 0.0001), and longer cardiopulmonary
      bypass time (p = 0.0001). Follow-up was 98% complete (3153 patient-years). There
      were 152 late deaths; 32 (21%) were considered valve-related: six
      thromboembolism, four valve thrombosis, five anticoagulant-related hemorrhage,
      eight prosthetic valve endocarditis, one paravalvular leak, and seven sudden
      death. The 5-year actuarial survival was 75%. Risk factors for late death
      included older age (p = 0.03), lower preoperative ejection fraction (p = 0.005),
      longer aortic crossclamp time (p = 0.001), longer cardiopulmonary bypass time (p
      = 0.0001), previous cardiac operation (p = 0.02), and higher preoperative
      functional class (p = 0.0001). Actuarial freedom at 5 years from major
      thromboembolic events and anticoagulant-related hemorrhage was 97% and 95%,
      respectively. This value for valve thrombosis was 99%, for reoperation 96%, for
      prosthetic valve endocarditis 98%, and for paravalvular leak 96%. Actuarial
      freedom from all valve-related events and valve-related death at 5 years was 74%
      and 94%, respectively. We conclude that the low incidence of valve-related events
      and low mortality supports the continued use of the St. Jude Medical valve.

PMID- 8302059
TI  - Outcome of mitral valve repair in patients with preoperative atrial fibrillation.
      Should the maze procedure be combined with mitral valvuloplasty?
AB  - To examine late outcome of mitral valve repair in patients with preoperative
      atrial fibrillation, we reviewed the cases of 323 consecutive patients who
      underwent mitral valvuloplasty for mitral regurgitation from 1980 to 1991;
      average age of 215 men and 108 women was 64 years (range 14 to 88 years), and 224
      patients (70%) were in New York Heart Association class III or IV before
      operation. The main indications for operation were severe mitral regurgitation
      (76%), coronary artery disease with associated mitral regurgitation (15%), and
      aortic valve disease (6%). At the time of mitral valve repair, coronary artery
      bypass grafting was done in 35% of patients, aortic valve replacement was done in
      7%, and multiple other procedures were done in 10%. For all patients, the 30-day
      mortality rate was 2.5% (70% confidence limits 1.6% to 3.4%) and survivorships at
      3 and 5 years were 81% and 76%, respectively. Before operation, 216 patients were
      in sinus rhythm and 97 patients had atrial fibrillation; in the latter group, 11
      had recent onset of atrial fibrillation within 3 months preceding mitral valve
      repair. Comparing patients with preoperative atrial fibrillation to those with
      sinus rhythm, we found no significant difference in operative mortality (3%
      versus 1.9%) or 5-year survivorship (74.3% +/- 6.3% versus 76.9% +/- 4.0%). At
      late follow-up, atrial fibrillation was present in 5% of patients with
      preoperative sinus rhythm, 80% of patients with preoperative chronic atrial
      fibrillation, and 0% of patients with preoperative recent onset atrial
      fibrillation (p < 0.01). The left atrial size by echocardiography was larger in
      patients with preoperative atrial fibrillation compared with that in those with
      sinus rhythm (59 +/- 1.4 mm versus 50.9 +/- 0.7 mm; p < 0.05). There was,
      however, only a weak correlation between preoperative left atrial size and late
      atrial fibrillation. Further, age, gender, and associated coronary artery disease
      did not correlate with presence of atrial fibrillation at late follow-up.
      Prevalence of late thromboembolic events was similar in patients with
      preoperative sinus rhythm compared with that in those with atrial fibrillation.
      These data suggest that mitral valve repair should be done before or soon after
      the onset of atrial fibrillation to maximize the chance of postoperative sinus
      rhythm and avoid long-term anticoagulation with warfarin. However, the early and
      late results of mitral valve repair in patients with chronic atrial fibrillation
      are good, and concomitant operation for supraventricular arrhythmia must have
      negligible morbidity and no adverse effect on operative mortality.

PMID- 8302060
TI  - The effects of complete versus incomplete mitral valve repair in experimental
      mitral regurgitation.
AB  - Severe mitral regurgitation (regurgitant fraction 0.75 +/- 0.02) was created in
      eight dogs by our closed-chest chordal rupture technique. After 3 months of
      chronic mitral regurgitation all indices of contractile function were depressed.
      Mitral valve repair was then attempted. Postoperative regurgitant fraction was
      reduced compared with the preoperative value in all eight dogs. Concomitantly,
      forward cardiac output increased in all dogs and pulmonary capillary wedge
      pressure fell in all dogs. However, in some dogs, significant regurgitation
      persisted despite repair. Postoperative regurgitant fraction ranged from 0% to
      60%. Postoperative residual regurgitant fraction was related significantly to
      postoperative cardiac output (r = 0.99), pulmonary capillary wedge pressure (r =
      0.77), ejection fraction (r = 0.75), and two indices of contractile function--the
      mass-corrected end-systolic stress volume relationship (r = 0.87) and end
      systolic stiffness (r = 0.93). In general, these parameters returned to their
      normal values before mitral regurgitation when postoperative regurgitant fraction
      was less than 30%. Myocytes isolated from the ventricles at the end of study also
      demonstrated normal contractile function when regurgitant fraction was less than
      30%.

PMID- 8302061
TI  - Aortic valve replacement with pulmonary homografts. Early experience.
AB  - The increasing use of the aortic homograft as aortic valve substitute and the
      limited availability of donor valves prompted us to consider the pulmonary
      homograft as an alternative substitute for aortic valve replacement. The aim of
      our study is to compare the ultrastructural and biomechanical properties of
      pulmonary homograft leaflets with those of their aortic counterpart and to
      present the early results of using the pulmonary homograft for aortic valve
      replacement. Light and transmission electron microscopy have shown that pulmonary
      homograft leaflets are thinner than the aortic with a lesser content of elastic
      tissue in the ventricularis layer. However there were no substantial differences
      in the ultrastructure. Uniaxial tensile tests were done on 69 cusps from human
      pulmonary and aortic valves using an Instron testing machine. The strain at 200
      KPa was found to be similar for both pulmonary and aortic leaflets (8.20% +/-
      2.87% versus 8.98% +/- 1.90%) cut circumferentially. Radial strips appear to be
      more extensible in pulmonary leaflets than in aortic (32.6% +/- 7.5% and 28.6% +/
      11.1%, respectively). The ultimate tensile strength for circumferential strips
      was found to be similar for both aortic and pulmonary valves (1460 +/- 857 kPa
      versus 1450 +/- 689 kPa), but there was relatively little difference between the
      radial strips (295 +/- 95 kPa versus 252 +/- 104 kPa). A total of 123 patients
      whose ages ranged between 13 and 78 years received either fresh antibiotic
      sterilized or cryopreserved pulmonary homografts for aortic valve replacement.
      The pulmonary homograft was inserted in place of the patient's diseased aortic
      valve by using one of two different techniques: freehand in the subcoronary
      position or as a "short cylinder" inside the aortic root. There was three
      hospital deaths (2.43%; 70% confidence limits = 1.08% to 4.83%). Cumulative
      follow-up was 184 patient-years (range 1 to 39 months). All surviving patients
      have been followed up with serial color flow Doppler echocardiography. There were
      no late deaths. Actuarial late survival was 97.5% (70% confidence limits = 95.7%
      to 98.6%) at 3 years. Four patients (2.2%/pt-yr) underwent reoperation because of
      severe aortic regurgitation (1, 4, 12, and 15 months after the operation) because
      of technical problems (mismatch in size between the pulmonary homograft and
      aortic anulus) in three patients and probably because of graft rejection in one
      patient. At 3 years the actuarial rate of freedom from reoperation was 95.5% (70%
      confidence limits = 92.7% to 97.3%). Mild aortic regurgitation has been detected
      in three patients (2.6%). No patients incurred thromboembolic episodes or
      infective endocarditis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8302062
TI  - Turbulent stresses downstream of three mechanical aortic valve prostheses in
      human beings.
AB  - High levels of turbulent stresses resulting from disturbed blood flow may cause
      damage to red blood cells and platelets. The purpose of this study was to
      evaluate the spatial distribution and temporal development of turbulent stresses
      downstream of three mechanical aortic valve prostheses in human subjects: the St.
      Jude Medical, the CarboMedics, and the Starr-Edwards silicone rubber ball. Blood
      velocity measurements were taken at 17 measuring points in the cross-sectional
      area of the ascending aorta 5 to 6 cm downstream of the aortic anulus with the
      use of a perivascular pulsed Doppler ultrasound system. Turbulence analysis was
      done for each of the 17 measuring points by calculating the radial Reynolds
      normal stresses within 50 msec overlapping time windows during systole. By
      coordinating the calculated Reynolds normal stress values for each time window
      and for all measuring points, computerized two-dimensional color-coded mapping of
      the turbulent stress distribution during systole was done. For the St. Jude
      Medical valves the highest Reynolds normal stress (27 to 63 N/m2) were found
      along the central slit near the vessel walls. The temporal development and
      spatial distribution of Reynolds normal stresses for the CarboMedics valves were
      quite similar to those of the St. Jude Medical valves with maximum Reynolds
      normal stress values ranging from 19 to 72 N/m2. The typical Reynolds normal
      stress distribution for the Starr-Edwards silicone rubber ball valves was
      asymmetric, revealing the highest Reynolds normal stresses (11 to 56 N/m2) at
      various locations in the annular region between the ball and the vessel wall. The
      spatial distribution and temporal development of turbulent stresses downstream of
      the three investigated mechanical aortic valve prostheses correlated well with
      the superstructure of the valves. The maximum Reynolds normal stresses for the
      three valve types were in the same order of magnitude with exposure times
      sufficient to cause sublethal damage to red blood cells and platelets.

PMID- 8302063
TI  - Proximal bypass to anomalous circumflex coronary artery.
AB  - A technique for coronary artery bypass to the proximal segment of an anomalous
      circumflex coronary artery is described. This technique has been used in four
      patients. It is suggested that in some situations this would be the preferable
      approach for bypassing an anomalous circumflex coronary artery obstruction.

PMID- 8302064
TI  - Retransplantation in heart-lung recipients with obliterative bronchiolitis.
AB  - Obliterative bronchiolitis remains the leading cause of morbidity and mortality
      in long-term survivors after heart-lung transplantation. Despite enhanced
      immunosuppressive therapy, a significant number of patients progress to end-stage
      respiratory failure, leaving retransplantation as the only potential therapeutic
      option. Between October 1986 and August 1990, 25 heart-lung recipients (mean age
      22 +/- 2 years) underwent repeat heart-lung transplantation at an average of 21
      months after their first procedure. Twenty-one patients (83%) were ventilator
      dependent at the time of retransplantation. The Kaplan-Meier survival at 1, 6,
      12, and 24 months was 52%, 33%, 25%, and 25%, respectively. Postoperative
      complications included bleeding, multisystem organ failure, and infection.
      Obliterative bronchiolitis resulted in death or graft failure in three patients
      between 12 and 36 months after the second transplantation. Five patients were
      currently alive at the time this article was written, with a median follow-up of
      54 months. Three were in New York Heart Association class I, and two had
      obliterative bronchiolitis with class III symptoms. Recently, we investigated the
      role of single lung retransplantation in nine heart-lung recipients (mean age 23
      +/- 3 years). The mean interval between procedures was 36 months, and eight
      patients (88%) were ventilator dependent. The Kaplan-Meier survival at 1, 6, 12,
      and 24 months was 89%, 67%, 67%, and 50%, respectively. We observed significantly
      less perioperative morbidity in this group. Five patients were alive (median
      follow-up 20 months); four were in New York Heart Association class I or II, and
      one was in New York Heart Association class III with recurrent obliterative
      bronchiolitis. We did not have enough patients to perform multivariate survival
      analysis. Survival curve comparisons with the use of the Wilcoxon test did show
      that the absence of performed antibodies in the recipient (panel reactive
      antibody frequency less than 10%) was associated with significantly improved
      survival after retransplantation. We also noted trends for improved survival in
      patients who had retransplantation at least 18 months after their original
      transplantation and in patients with negative preoperative sputum cultures.
      Retransplantation is a high-risk procedure that can result in rehabilitation in
      otherwise incapacitated patients. Single lung retransplantation appears to be the
      preferred option in carefully selected patients.

PMID- 8302065
TI  - Results of single and bilateral lung transplantation in 131 consecutive
      recipients. Washington University Lung Transplant Group.
AB  - We reviewed results of the first 131 recipients who received a single or
      bilateral sequential lung transplant at Barnes Hospital between July 1, 1988, and
      July 31, 1992. Follow-up data were complete as of January 1, 1993, for a minimum
      of 5 months' follow-up for all surviving recipients. There were 11 hospital
      deaths for an overall 92% hospital survival. Thirteen late deaths occurred and
      107 (81%) recipients remain alive with a median follow-up period of 19 months.
      One hundred nineteen recipients survived at least 3 months after transplantation,
      and for this group factors that might influence long-term results were evaluated.
      The prevalence of pathologically proved bronchiolitis obliterans was 18.5%.
      Functional deterioration, which may not correlate with pathologic findings, was
      evaluated with a recently developed bronchiolitis obliterans syndrome staging
      system. Factors not influencing long-term outcome included the number of early
      rejection episodes, matching donor and recipient cytomegalovirus antibody status,
      or underlying diagnosis. Patients undergoing single lung transplantation for
      primary pulmonary hypertension or Eisenmenger's syndrome had results similar to
      those of other diagnostic groups. Furthermore, the hemodynamic improvement
      previously reported for this group of patients after single lung transplantation
      has been maintained at long-term follow-up. The shortage of donor organs and the
      need for improved methods for diagnosis and management of chronic rejection
      remain the most challenging problems in lung transplantation.

PMID- 8302066
TI  - Eight years' experience with bridging to cardiac transplantation.
AB  - Although bridging to cardiac transplantation has become a therapeutic option for
      transplant candidates whose condition deteriorates while they are awaiting a
      donor heart, short-term efficacy has not been proved and long-term survival has
      not been reported. We retrospectively reviewed data on 44 patients who had
      circulatory assist devices placed as a bridge to transplantation between May 1985
      and April 1993. The 35 male and nine female patients ranged in age from 12 to 65
      years (mean 43.8 years). Thirty-one patients were supported with 32 Thoratec (18
      left ventricular, 14 biventricular), 11 Novacor, and two Jarvik J-7-70 devices.
      The duration of device support was from 4 hours to 440 days (mean 45.5 days).
      Fifteen patients did not receive a donor organ because of infection (ten
      patients), renal failure (five patients), bleeding (nine patients),
      cerebrovascular accident (three patients), ventricular fibrillation (one
      patient), and right heart failure (one patient), and all died. Two patients were
      weaned from support and survived without transplantation. Twenty-seven patients
      underwent transplantation, and 26 survived (96%). Overall survival was 64%
      (28/44). Duration of survival ranged from 2 to 96 months (mean 35 months). Among
      the 28 hospital survivors, there were four late deaths (all transplant
      recipients) at 3, 6, 14, and 68 months. Posttransplantation actuarial survivals
      at 1, 5, and 8 years are 88%, 83%, and 66%. Twenty-three of the 24 patients
      presently alive are in New York Heart Association functional class I. These data
      demonstrate the short- and long-term efficacy of bridging to transplantation with
      circulatory support devices. The excellent survival and full functional recovery
      of patients undergoing transplantation ensure that donor organs are not being
      "wasted" on the sickest patients.

PMID- 8302067
TI  - Purine efflux from transplanted human cardiac allografts. Correlation with graft
      function.
AB  - Purine efflux from transplanted human cardiac allografts was investigated as a
      potential biochemical correlate to graft preservation and eventual function.
      Coronary sinus effluent from 14 allografts was sampled at 1, 5, 10, 15, 20, and
      25 minutes after reperfusion. The plasma fraction from each sample was analyzed
      for hypoxanthine, xanthine, urate, inosine, and adenosine by high-performance
      liquid chromatography. Total organ preservation time, aortic crossclamp and
      bypass times, and initial cardiac index off bypass were recorded. An inotropic
      score was calculated from the dosages of inotropic agents each recipient required
      immediately after transplantation. Inosine and adenosine were not detectable in
      the coronary sinus effluent at any time during reperfusion. Hypoxanthine
      concentration rose sevenfold (p < 0.001) 1 minute after reperfusion. Xanthine
      concentration peaked later at 5 minutes after reperfusion, a twofold increase (p
      < 0.02). As reperfusion continued, hypoxanthine and xanthine concentrations
      returned toward baseline levels. The rise in coronary sinus xanthine
      concentration provides evidence for hypoxanthine degradation by xanthine oxidase
      during the immediate reperfusion period. The extent of hypoxanthine efflux
      correlated with total graft ischemic time (p < 0.05), inotropic score (p <
      0.005), and the time from crossclamp release to cessation of bypass (p < 0.01).
      Hypoxanthine efflux can be used as a sensitive and objective biochemical
      indicator of graft preservation and immediate function.

PMID- 8302068
TI  - Clinically relevant diaphragmatic dysfunction after cardiac operations.
AB  - Phrenic nerve injury and diaphragmatic dysfunction can be induced by cardiac
      operation. The clinical consequences are not well-established. We evaluated 13
      consecutive patients over a 2-year period with unexplained and prolonged
      difficulties in weaning from mechanical ventilation. The mean time of measurement
      from the operation day was 31 +/- 19 days (range 8 to 78). With the same
      technique we also evaluated 12 control patients: four patients at day 1 after
      cardiac operation while they were still intubated; four normally convalescing
      patients at day 7 or 8 after cardiac operation; and four patients who required
      prolonged mechanical ventilation because of another identified cause after
      cardiac operation. Diaphragmatic function was evaluated at the bedside from
      esophageal and gastric pressure measurements. A low or negative ratio of gastric
      pressure swing to transdiaphragmatic pressure swing, indicative of diaphragm
      dysfunction, was found in all 13 patients (mean -0.39 +/- 0.64). The difference
      between the 13 patients and all control groups was found to be highly
      significant. Transdiaphragmatic pressure measured during a maximal voluntary
      inspiratory effort and transdiaphragmatic pressure measured during a short, sharp
      sniff were markedly diminished (28 +/- 18 cm H2O and 13 +/- 15 cm H2O,
      respectively) in the 13 patients, significantly different from values in the four
      control patients studied at day 7 or 8. Transdiaphragmatic pressure measured
      after magnetic stimulation in four patients was also markedly reduced (7 +/- 5 cm
      H2O) as compared with normal theoretic values. Aminophylline infusion had no
      effect on any of these parameters. In one of two patients evaluated a second
      time, about 5 weeks later, a marked improvement was observed. Estimating the
      prevalence of clinically relevant diaphragmatic dysfunction, we found it to be
      0.5% when no topical cooling was used and 2.1% when iced slush with no insulation
      pad was added for myocardial protection (p < 0.005). The most striking finding
      was that the clinical course of the 13 patients was marked by severe intercurrent
      events, including cardiorespiratory arrest after early tracheal extubation in 5
      patients, nosocomial pneumonia in 11, prolonged mechanical ventilation in all (58
      +/- 41 days), and a fatal outcome in 3. We conclude that prolonged postoperative
      diaphragmatic dysfunction may cause severe life-threatening complications after
      cardiac operation and can be limited to some extent by avoiding the use of iced
      slush topical cooling of the heart.

PMID- 8302069
TI  - Inhomogeneous and complementary antegrade and retrograde delivery of cardioplegic
      solution in the absence of coronary artery obstruction.
AB  - Inhomogeneous delivery of cardioplegic solution may result in postischemic
      myocardial injury. This study compares the distribution of warm blood antegrade
      and retrograde cardioplegia to multiple discrete left ventricular myocardial
      regions in pigs with unobstructed coronary arteries. Cardioplegic solution was
      delivered antegradely and retrogradely at 150 ml/min, and flows to 1152
      individual myocardial regions were determined twice for each route with four
      different radiolabeled microspheres. The antegrade system delivered greater flow
      to each gram of myocardium than did the retrograde system (1.37 +/- 0.31 versus
      0.39 +/- 0.09 ml/gm per minute, p < 0.001). Flow to individual myocardial regions
      was significantly inhomogeneous for both antegrade and retrograde cardioplegia,
      but much more so for retrograde cardioplegia (coefficient of variation was 48% +/
      17% for antegrade cardioplegia and 106% +/- 16% for retrograde cardioplegia; p <
      0.001). The pattern of flow to individual myocardial regions was highly
      reproducible for a given route of delivery as confirmed by repeated measurements
      with different radioactive microsphere isotopes (correlation coefficients 0.88 +/
      0.12 for AC1-AC2 and 0.84 +/- 0.10 RC1-RC2), but antegrade cardioplegia and
      retrograde cardioplegia patterns were significantly different and therefore
      complementary (correlation coefficients 0.03 +/- 0.04, p < 0.001). These findings
      support the routine combined use of antegrade cardioplegia and retrograde
      cardioplegia to enhance delivery of cardioplegic solution to all regions of the
      heart and minimize the potential risk of postischemic myocardial dysfunction.

PMID- 8302070
TI  - Oxygen radical-mediated vascular injury selectively inhibits receptor-dependent
      release of nitric oxide from canine coronary arteries.
AB  - Reperfusion after global cardiac ischemia may injure coronary artery endothelium
      and lead to vasospasm and thrombosis. Oxygen-derived radicals have been
      implicated as mediators of this process, but the precise mechanism of injury is
      unknown. We hypothesized that oxygen-derived radicals impair coronary endothelial
      production of nitric oxide, a potent endogenous vasodilator and inhibitor of
      platelet adhesion. To test this theory, we developed an in vitro model of
      reperfusion injury in which segments of epicardial canine coronary artery were
      suspended in organ chambers (physiologic salt solution, 37 degrees C, 95% oxygen
      and 5% carbon dioxide) and exposed to oxygen-derived radicals (generated by
      adding xanthine [10(-4) mol/L] and xanthine oxidase [100 mU/ml] to the bathing
      solution for 70 minutes). After exposure to oxygen-derived radicals, epicardial
      coronary artery smooth muscle exhibited normal contraction to potassium ions (20
      mmol/L) and prostaglandin F2 (4 x 10(-6) mol/L); also, the rings relaxed normally
      on exposure to isoproterenol and sodium nitroprusside (10(-9) to 10(-4) mol/L) (n
      = 6). In contrast, endothelium-dependent vasodilatation to receptor-dependent
      agonists acetylcholine and adenosine diphosphate (10(-9) to 10(-4) mol/L) was
      impaired as compared with the reaction of control vessels not exposed to oxygen
      derived radicals (n = 18, P < 0.001, and n = 10, P < 0.002, respectively).
      Importantly, receptor-independent, endothelium-dependent relaxation to the
      calcium ionophore A23187 was normal (n = 6). Further, endothelium-dependent
      vasodilatation to receptor-dependent agonist bradykinin (non-nitric oxide
      pathway) was normal after exposure to oxygen-derived radicals. This is the first
      study to demonstrate that oxygen-derived radicals selectively impair receptor
      dependent nitric oxide production by the coronary endothelium. Diminished nitric
      oxide production is a likely mechanism of vasospasm and thrombosis after
      reperfusion of the ischemic heart.

PMID- 8302071
TI  - Optimal flow rates for retrograde warm cardioplegia.
AB  - Retrograde delivery of warm blood cardioplegia may improve nutrient cardioplegic
      flow beyond coronary obstructions, but may not adequately perfuse the right
      ventricle and the posterior left ventricle. To determine the optimal flow rate
      for warm retrograde cardioplegia, we assessed 62 patients undergoing elective
      coronary artery bypass in two studies. In the low flow study, administration of
      50 ml/min (n = 9), 75 ml/min (n = 11), or 100 ml/min (n = 7) was associated with
      high lactate production and oxygen extraction during cardioplegic administration.
      At 50 minutes of cardioplegic arrest, the coronary venous effluent pH was low in
      all groups. In the high flow study, 30 patients all received flow rates of 100,
      200, and 300 ml/min in randomized order during the crossclamp period. In
      addition, five patients received cardioplegia at a rate of 500 ml/min for the
      duration of the crossclamp period. Administration of 200 ml/min or higher
      minimized lactate production and maintained coronary venous pH within the
      physiologic range, but flows of 300 ml/min or higher did not increase oxygen use
      or reduce lactate or acid production. Patients in the low flow groups had
      significantly greater myocardial lactate release during cardioplegic infusion and
      after removal of the crossclamp than the high flow group. Warm retrograde
      cardioplegia should be delivered at flow rates of at least 200 ml/min during
      elective coronary artery bypass operations.

PMID- 8302072
TI  - Developmental differences in myocardial protection in response to 5'-nucleotidase
      inhibition.
AB  - Age-related differences in the activity of 5'-nucleotidase, an enzyme responsible
      for conversion of high-energy phosphates to their the diffusible precursors, may
      help to explain age-related differences in tolerance of global myocardial
      ischemia. Postischemic function and high-energy phosphate content were measured
      in the hearts of rabbits 7 to 10 days old (neonate), 30 to 40 days old (1 month),
      and 6 to 12 months old (adult). Hearts in each age group were subjected to 60
      minutes of ischemia at 34 degrees C either with no cardioplegia, with unmodified
      St. Thomas' Hospital cardioplegic solution, or with St. Thomas' Hospital
      cardioplegic solution with pentoxifylline, a 5'-nucleotidase inhibitor. These
      groups were compared with one another and with control hearts that were
      continuously perfused for 1 hour. In adults, addition of pentoxifylline to St.
      Thomas' Hospital cardioplegic solution restored adenosine triphosphate and total
      nondiffusible nucleotide levels to control values and improved recovery of
      cardiac output and developed pressure compared with results with unmodified St.
      Thomas' Hospital cardioplegic solution. In contrast, biochemical and functional
      parameters in neonatal hearts were not affected by either unmodified St. Thomas'
      Hospital cardioplegic solution cardioplegia or St. Thomas' Hospital cardioplegic
      solution with pentoxifylline. Functional recovery in neonatal hearts subjected to
      unprotected ischemia was superior to that in the older age groups. In 1-month-old
      hearts, St. Thomas' Hospital cardioplegia improved recovery compared with
      recovery after unprotected ischemia, but no incremental improvement in function
      or high-energy stores was seen with addition of pentoxifylline. The lack of
      effect of pentoxifylline on neonatal hearts suggest that there is a relative
      deficiency of 5'-nucleotidase in this age group. This may contribute to the
      improved functional recovery observed in unprotected hearts. Furthermore,
      addition of pentoxifylline to adult hearts appears to confer the benefits of low
      5'-nucleotidase activity occurring naturally in the neonate.

PMID- 8302073
TI  - Effects of cardioplegic arrest on left ventricular systolic and diastolic
      function of the intact neonatal heart.
AB  - The effects of cardiopulmonary bypass and cardioplegic arrest on left ventricular
      systolic and diastolic function were studied in 20 intact neonatal lambs
      instrumented with ultrasonic dimension transducers and micromanometers for
      collection of left ventricular pressure-dimension data. Group I lambs underwent 2
      hours of hypothermic cardiopulmonary bypass (25 degrees C) alone; group II lambs
      underwent 2 hours of hypothermic cardiopulmonary bypass (25 degrees C) with 1
      hour of multidose, cold, crystalloid cardioplegic arrest (St. Thomas' Hospital
      No. 2 solution). The control neonatal lamb left ventricle was found to be
      relatively stiff, with the limit of diastolic filling reached at physiologic left
      ventricular filling pressures, resulting in apparent descending limbs of left
      ventricular function. After cardiopulmonary bypass, identical results were
      obtained in groups I and II. A significant loss of left ventricular compliance
      limited left ventricular performance via two mechanisms. First, left ventricular
      preload was significantly decreased, with a concomitant diminution in left
      ventricular stroke work; afterload (pressure work) was maintained at the expense
      of volume work (flow), which declined significantly. Second, preload behaved as
      though fixed, resulting in a loss of impedance matching (afterload mismatch).
      Although contractility as assessed by the end-systolic pressure-dimension
      relationship was significantly increased (because of increased levels of
      circulating catecholamines), global systolic performance as quantified by the
      stroke work/end-diastolic length relationship remained unchanged, reflecting the
      afterload sensitivity of the latter parameter in the face of fixed preload. We
      conclude that cardiopulmonary bypass in the intact neonate results in a loss of
      compliance and impedance matching rather than a loss of contractility; however,
      the addition of 1 hour of cold, crystalloid cardioplegic arrest results in no
      dysfunction beyond that attributable to cardiopulmonary bypass alone.

PMID- 8302074
TI  - Complete prevention of postischemic spinal cord injury by means of regional
      infusion with hypothermic saline and adenosine.
AB  - Spinal cord injury after operations on the descending thoracic and
      thoracoabdominal aorta remains a persistent clinical problem. Previous attempts
      to decrease the risk of this devastating complication by lowering the rate of
      metabolism of the spinal cord have met with varying success. We hypothesized that
      the tolerance of the spinal cord to an ischemic insult could be improved by means
      of adenosine. Twenty New Zealand white rabbits underwent 40 minutes of isolated
      infrarenal aortic occlusion after heparin anticoagulation. Clamps were placed
      both below the left renal vein and above the aortic bifurcation. In 10 rabbits
      (group A), a bolus of adenosine (100 mg) was infused into the isolated aortic
      segment immediately after crossclamping and this bolus was followed by a flush of
      hypothermic saline (8 degrees C, 30 ml/kg) over the first 10 minutes of ischemia.
      In one control group of five animals (group B), the descending infrarenal aorta
      was crossclamped without infusion of adenosine or saline. In another control
      group of five animals (group C), the aortic segment was flushed with normothermic
      saline (37 degrees C) in a fashion identical to that of the study group. The
      aortic clamps were removed after 40 minutes, the abdomen was closed, and the
      animals were allowed to recover from anesthesia. Spinal cord function was
      assessed 12, 24, 48, 72, and 96 hours after operation by the Tarlov scale. All
      animals were put to death at 96 hours after operation and spinal cords were
      harvested for histologic analysis. The spinal cord function of all group A
      animals was fully intact with Tarlov scores of 5; group B and group C animals
      were all paraplegic with Tarlov scores of 0 (p < 0.001, general linear models
      analysis of variance). Histologic examination of spinal cords from group A
      rabbits revealed no evidence of cord injury, whereas spinal cords from groups B
      and C had evidence of extensive cord injury with central gray necrosis, axonal
      swelling, dissolution of Nissl substance, and astrocyte and macrophage
      infiltration. Regional infusion of the crossclamped infrarenal rabbit aorta with
      hypothermic saline and adenosine completely prevented paraplegia in our model
      despite a 40-minute ischemic insult.

PMID- 8302075
TI  - Thrombin regulation in congenital heart disease after cardiopulmonary bypass
      operations.
AB  - Children with cyanotic congenital heart disease who undergo operation with
      cardiopulmonary bypass are at increased risk of thromboembolic or hemorrhagic
      complications, or both. Regulation of thrombin, a key enzyme in coagulation, is
      essential in preventing these complications. We therefore examined the in vitro
      capacity of plasma from 15 children with cyanotic congenital heart disease to
      generate thrombin and to inhibit 125I-thrombin before and after cardiopulmonary
      bypass. We also assessed whether thrombin had been generated in vivo by assaying
      levels of fibrinogen, thrombin-antithrombin III complexes, and D-dimer. Plasma
      levels of the thrombin inhibitors, antithrombin III, alpha-2-macroglobulin, and
      heparin cofactor II were also measured. Thrombin regulation was normal before
      operation. After cardiopulmonary bypass, the in vitro capacity to generate
      thrombin decreased by 50%, and this was primarily a result of hemodilution (31%).
      Similar postoperative decreases were noted in the levels of antithrombin III,
      heparin cofactor II, and alpha-2-macroglobulin (26% to 45%). However, the total
      in vitro plasma thrombin inhibitory capacity decreased by only 13%. Levels of
      thrombin-antithrombin III and D-dimer increased after operation, indicating that
      thrombin had been generated and inhibited in vivo. Clinically, there were no
      thromboembolic complications although six patients required replacement therapy
      for excessive small-vessel bleeding. In conclusion, thrombin regulation is
      significantly altered after cardiopulmonary bypass. Although thrombin is
      generated in vivo, the total residual capacity to do so is impaired because of
      hemodilution. Despite a concomitant decrease in thrombin inhibitor levels, the
      total residual in vitro capacity of plasma to inhibit thrombin is relatively
      spared. This suggests that after cardiopulmonary bypass the risk of hemorrhagic
      complications after an additional hemostatic challenge is relatively greater than
      the risk of thrombotic complications. This might be reflected in the predominance
      of hemorrhagic complications in our patients.

PMID- 8302076
TI  - Evaluation of the pulsatility of a new pulsatile left ventricular assist device-
      the integrated cardioassist catheter--in dogs.
AB  - A new pulsatile left ventricle-femoral artery bypass system (integrated
      cardioassist catheter system) has been developed for rapid, percutaneous
      insertion as a left ventricular assist device. Previous experiments revealed its
      superiority over the intraaortic balloon pump system in maintaining the
      peripheral circulation and in improving myocardial blood flow and afterload. Our
      objective was to determine whether the pulsatility of left ventricular bypass of
      this system would be preferable for maintaining the peripheral circulation and
      managing the ischemic myocardium as compared with nonpulsatile left ventricular
      bypass. Ten dogs with profound heart failure were supported by this system. Their
      hemodynamic status and myocardial blood flow were measured under control,
      nonpulsatile left ventricular bypass, or synchronous pulsatile left ventricular
      bypass. Significant differences between the nonpulsatile bypass group and the
      pulsatile bypass group were observed in the mean increase in aortic pressure
      (3.5% versus 22.2%, respectively; p < 0.001), total cardiac output (13.0% versus
      21.7%; p = 0.004), and myocardial blood flow (9.5% versus 21.8%; p < 0.001). No
      differences were found between groups in the decrease in left atrial pressure (
      20.2% versus -20.2%; p > 0.05). The ratio of diastolic time index/tension time
      index was shown to be improved significantly in the pulsatile bypass group
      compared with that of control and nonpulsatile bypass groups (p < 0.001). Thus,
      the pulsatility of the integrated cardioassist catheter system may support the
      peripheral circulation and improve the myocardial blood flow and oxygen
      supply/demand ratio.

PMID- 8302077
TI  - Survival related to nodal status after sleeve resection for lung cancer.
AB  - Sleeve lobectomy is a lung-saving procedure indicated for central tumors for
      which the alternative is a pneumonectomy. The relation between survival and nodal
      status is controversial because, in most series, the presence of N1 disease
      adversely affects the prognosis with few or no long-term survivors. During the
      period 1972 to 1992, 142 patients underwent sleeve resection for lung cancer at
      our institution. Mean age (+/- standard deviation) was 60.7 +/- 9.1 years (range
      11 to 78 years), and indications for operation were a central tumor in 112
      patients (79%), a peripheral tumor in 18 patients (13%), and compromised
      pulmonary function in 12 patients (8%). Histologic type was predominantly
      squamous (72.5%) followed by nonsquamous (24.6%) and carcinoid tumors (2.8%).
      Resection was complete in 124 patients (87%) and incomplete in 18 (13%), and the
      operative mortality was 2.1% (n = 3). Follow-up was complete for the 139
      remaining patients. Including operative deaths, survivals at 5 and 10 years for
      all patients were 46% (95% confidence intervals 38% to 55%) and 33% (95%
      confidence intervals 24% to 42%), respectively. For patients with N0 status (n =
      73), 5- and 10-year survivals were 57% (95% confidence intervals 45% to 69%) and
      46% (95% confidence intervals 32% to 60%); for patients with N1 status (n = 55),
      these rates were 46% (95% confidence intervals 32% to 60%) and 27% (95%
      confidence intervals 14% to 40%) (p = 0.13). No patient with N2 status (n = 14)
      survived 5 years. Local recurrences occurred in 23% of cases, but the prevalence
      was not statistically different between patients with N0 disease (16.6%) and N1
      disease (23.1%) (p = 0.43). These data suggest that sleeve resection is an
      adequate operation for patients with resectable lung cancer and N0 N1 status. The
      presence of N2 disease significantly worsens the prognosis and may contraindicate
      the use of the procedure.

PMID- 8302078
TI  - Prospective evaluation of unilateral adrenal masses in patients with operable non
      small-cell lung cancer. Impact of magnetic resonance imaging.
AB  - We designed a prospective study to evaluate the accuracy of magnetic resonance
      imaging in distinguishing a benign from a malignant adrenal mass in patients with
      otherwise operable non-small-cell lung cancer. METHODS: Potentially operable non
      small-cell lung cancer was prospectively staged. If a unilateral adrenal mass was
      found by computed tomographic scanning, respiratory compensated and cardiac gated
      thin section magnetic resonance imaging of the adrenal glands was done. One
      radiologist interpreted the magnetic resonance imaging scan blinded and, on the
      basis of the relative signal strengths of the T1- and T2-weighted images, judged
      whether the adrenal mass was benign or malignant. The patients then underwent a
      percutaneous needle biopsy of the adrenal mass, if technically feasible. If the
      result of the needle biopsy was nondiagnostic or if the biopsy was not feasible,
      an adrenalectomy through a posterior approach was performed. RESULTS: Twenty
      seven patients with a unilateral adrenal mass entered the study-11 men and 16
      women whose ages ranged from 42 to 75 years (median 58 years). Four patients had
      epidermoid and 23 adenocarcinoma of the lung. The clinical locoregional stage was
      I in 9, II in 1, IIIA in 16, and IIIB in 1. Twenty-five completed the magnetic
      resonance imaging procedure. Five adrenal masses (19%) were metastatic non-small
      cell lung cancer (adenocarcinoma = 4, epidermoid = 1); 22 masses (81%) were
      benign (adenoma = 20, hyperplasia = 2). There were no significant differences in
      age, sex, histologic type, or locoregional stage between those with a benign
      versus a malignant mass. However, the malignant masses were significantly larger
      (3.8 +/- 1.9 cm; range 2.5 to 7.1; median 3.1) than the benign masses (2.0 +/-
      0.4 cm, range 1.2 to 2.8; median 2.0) (p < 0.001). Among those having magnetic
      resonance imaging (n = 25), the technique correctly predicted a malignant mass in
      the four patients with a histologically confirmed metastasis from non-small-cell
      lung cancer. However, among the 21 histologically benign masses, the magnetic
      resonance imaging was interpreted as benign in 5, malignant in 14, and
      indeterminate in 2. Therefore, although the false-negative rate was 0%, the false
      positive rate was 67%. CONCLUSION: Most adrenal masses in patients with otherwise
      operable non-small-cell lung cancer are benign. Currently available magnetic
      resonance imaging methods cannot replace biopsy.

PMID- 8302079
TI  - Safety of absorbable suture for sternal closure after pulmonary or mediastinal
      resection.
AB  - The reliability of polyglyconate monofilament (Maxon) suture for sternal closure
      was tested on 216 consecutive sternotomies, performed on 208 patients in our
      department from January 1986 to December 1990. The reason of sternotomy was
      primary lung cancer in 34 cases (16%), lung metastases in 127 (59%), and
      disorders of the thymus in 55 (25%). Mean age was 38 years (range 3 to 78 years);
      multiple lung resections were performed in 102 patients (average 7 lesions, range
      2 to 30); maximum extent of the operation was pneumonectomy in 2 cases, lobectomy
      in 53, segmentectomy in 27, and wedge resection in 74. Prior chemotherapy had
      been administered in 75 cases (35%). A second sternotomy was performed in 8
      cases. No cases of sternal dehiscence, sternal infection, or empyema were
      observed, after a median follow-up of 27 months. Overall perioperative mortality
      was 0.9% (2/216). Our series demonstrates the safety of polyglyconate
      monofilament (Maxon) suture for sternal closure. Absorbable sutures appear to be
      a safe alternative to steel wire closure in patients undergoing extended
      pulmonary or mediastinal resection.

PMID- 8302080
TI  - Temporary and permanent restoration of airway continuity with the tracheal T
      tube.
AB  - The advantages of the tracheal T-tube compared with a regular tracheostomy tube
      are a physiologic direction of air flow, preservation of laryngeal phonation, and
      superior patient acceptance. Between 1968 and 1991, 140 patients aged 7 months to
      95 years underwent placement of T-, TY- (n = 7), or a modified extended T-tube (n
      = 4). Primary diagnosis was postintubation stenosis in 86 patients, burn injury
      in 13 patients, malignant airway tumors in 12 patients, and various disorders in
      29 patients. Stenting with a silicone rubber tube was temporary in 31 patients
      and 14 underwent later operative reconstruction. Definitive permanent insertion
      was performed in 49 patients. A modified tube was used in 4 patients with left
      main bronchial stenosis with effective long-term palliation in 3. Postoperative
      airway obstruction prompted placement in 32 patients. Positioning of the T-tube
      above the vocal cords in 12 patients for subglottic stenosis was effective in 10.
      The T-tube was not tolerated in 28 patients (20%) because of obstruction of the
      upper limb or aspiration. Five of 10 patients under the age of 10 years had
      airway obstruction necessitating tube removal. Long-term intubation in 112
      patients exceeded 1 year in 49 patients and 5 years in 12 patients. Only 5
      patients required tube removal for obstructive problems more than 2 months after
      placement. The tracheal T-tube restores airway patency reliably with excellent
      long-term results and represents the preferred management of chronic airway
      obstruction not amenable to surgical reconstruction.

PMID- 8302081
TI  - Lung resection after high doses of mediastinal radiotherapy (sixty grays or
      more). Reinforcement of bronchial healing with thoracic muscle flaps in nine
      cases.
AB  - Mediastinal radiotherapy of more than 60 Gy highly compromises bronchial and
      wound healing after lung resection. Nine patients with primary lung cancers
      underwent radical resection after high radiation doses. Eight patients had
      primary lung cancer previously treated by radiotherapy alone (n = 2) or
      associated with chemotherapy (n = 6). One patient had a tracheal cancer involving
      the carina that was previously treated by radiotherapy. Seven patients underwent
      pneumonectomy and one patient underwent lobectomy with reinforcement of bronchial
      stump closure with use of the serratus anterior muscle. One patient underwent a
      sleeve lobectomy with bronchial reconstruction wrapped with an intercostal
      pedicle flap. Five patients had no postoperative complications and four patients
      had empyema, one associated with a small bronchial fistula. All except one
      patient were successfully treated by thoracostomy and immediate or secondary
      transposition of the pectoralis major muscle and the omentum to fill the cavity.
      These results show that lung resections can be done after high doses of
      radiotherapy without a high rate of bronchial fistula by using thoracic muscle
      flaps to reinforce bronchial stumps and anastomoses. In this procedure, surgical
      dissection is more time-consuming and increases the postoperative empyema rate
      (4/9). However, the higher long-term survival may justify this choice in selected
      cases.

PMID- 8302082
TI  - Pulmonary hamartoma and malignancy.
AB  - Sixty-five patients, aged 15 to 65 years, including 48 men (73.8%), were operated
      on for pulmonary (60) or endobronchial (5) hamartoma: there were 36 enucleations,
      17 lobectomies (1 sleeve resection), 7 wedge resections, 4 segmentectomies, and 1
      pneumonectomy. The average tumor diameter was between 2 and 4 cm; 15 were
      calcified. All were benign. Two were parts of an incomplete Carney's triad. Eight
      were associated with carcinomas, and three of these were bronchial carcinomas.
      Concerning these latter three tumors, a study of the incidence tables for
      northern France and of the standardized mortality ratio showed that the risk of
      bronchial cancer developing in patients with hamartoma, after a sufficient follow
      up (61 patients), was multiplied by 6.66, and the chi 2 test showed a significant
      difference of incidence compared with that in the general population (p < 0.001).
      It is concluded that patients with hamartoma should be submitted to a complete
      evaluation and to a regular follow-up.

PMID- 8302083
TI  - Thymic carcinoma. Ten years' experience in twenty patients.
AB  - Thymic carcinoma is a rare neoplasm with extremely poor prognosis. To evaluate
      the outcome of treatment in thymic carcinoma, we reviewed a 10-year (1982 to
      1992) experience with 20 consecutive patients in Taichung Veterans General
      Hospital. There were 9 men and 11 women: ages ranged from 34 to 70 years old
      (mean 51.4 years). None of these patients had concomitant myasthenia gravis. All
      of the patients received surgical intervention, and the diagnosis was made by
      pathologic study. Postoperative staging was made according to the modified
      Masaoka staging system. None of our patients were in stage I. One patient (5%)
      had stage II disease, 12 (60%) stage III, and 7 (35%) stage IV. The pathologic
      subtypes of thymic carcinoma included eight squamous cell carcinomas, seven
      undifferentiated carcinomas, one lymphoepithelioma-like carcinoma, one clear-cell
      carcinoma, 1 mucoepidermoid carcinoma, and two carcinoid tumors. Curative
      resection could be done in seven patients (35%). The overall cumulative survival
      was 45.9% at 3 years and 34.4% at 5 years. The median survival times for patients
      with complete and incomplete resection were 39.0 months and 14.3 months,
      respectively (p = 0.1752). The median survival times of patients with
      postoperative radiotherapy and without postoperative radiotherapy were 39.3
      months and 15.0 months, respectively (p = 0.0738). The median survival times of
      patients with squamous cell carcinoma and undifferentiated carcinoma were 25.4
      months and 11.3 months, respectively (p = 0.1464). Our data show that complete
      resection, postoperative radiotherapy, and squamous cell carcinoma do not
      indicate a significantly favorable result, even though they result in longer
      median survival times. Yet a positive trend of favorable outcome in patients who
      received postoperative radiotherapy is ambiguously shown.

PMID- 8302084
TI  - Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary
      bypass.

PMID- 8302085
TI  - Routine dexamethasone therapy for cardiac operations?

PMID- 8302086
TI  - Combined treatment of mitral stenosis and atrial fibrillation with valvuloplasty
      and a left atrial maze procedure.

PMID- 8302087
TI  - Immunosuppressive treatment of venous allografts in dogs.

PMID- 8302088
TI  - Direct enlargement of isolated coronary artery ostial stenosis.

PMID- 8302089
TI  - Antiadhesive membranes for cardiac reoperations.

PMID- 8302090
TI  - Clinical evaluation of the omniscience cardiac valve prosthesis (J Thorac
      Cardiovasc Surg 1992; 103:259-66)

PMID- 8302091
TI  - Bronchopleural fistula: the use of tissue glue.

PMID- 8302092
TI  - Coronary compression after arterial switch procedure.

PMID- 8302093
TI  - A simple method for intraoperative visualization of the repaired aortic valve.

PMID- 8302094
TI  - Severe calcification of a parietal pericardial patch used in an aortic root
      enlargement: case report.

PMID- 8302095
TI  - Grafting of chordae tendineae: a new technique for the repair of mitral
      insufficiency caused by ruptured chordae of the anterior leaflet.

PMID- 8302096
TI  - Transesophageal echocardiography for the diagnosis of traumatic injury of the
      thoracic aorta.

PMID- 8302097
TI  - Ascending aortic aneurysm eroding the chest wall: repair avoiding a median
      sternotomy.

PMID- 8302098
TI  - The balloon inflation technique to confirm good placement of the retroplegia
      cannula.

PMID- 8302099
TI  - Does flow character of cardiopulmonary bypass make a difference?

PMID- 8302100
TI  - Reactivity of gastroepiploic and internal mammary arteries.

PMID- 8302101
TI  - Simultaneous norepinephrine-prostacyclin biatrial infusion for right ventricular
      failure after transplantation.

PMID- 8302102
TI  - The endocardial versus the epicardial approach: still a controversy?

PMID- 8302103
TI  - Physician and practice characteristics associated with judgments about breast
      cancer treatment.
AB  - Since most cancer is treated in the local community, the judgments of primary
      care physicians about treatment of breast cancer are important. This study
      examined physician and practice characteristics associated with physician
      judgments about the treatment of Stage I and Stage II breast cancer. Data are
      combined from samples of 3,436 physicians: physicians affiliated with hospitals
      participating in the Community Clinical Oncology Program (CCOP) and a national
      sample of non-CCOP physicians. This study focused on 1,460 physicians who had
      seen breast cancer patients and participated in treatment decision-making.
      Judgments were elicited using brief vignettes. Judgments were more variable for
      Stage I than for Stage II treatments. Judgments consistent with the NIH Consensus
      Conferences on breast cancer were more likely from surgeons, physicians who
      participated in information networks focused on cancer, and those with more
      breast cancer patients. Concurrence with the consensus conference positions was
      less likely in older physicians and those in solo practice. These findings point
      to structures that reinforce quality of care, particularly those that enhance
      communication, such as group practice or the activities of hospital staffs,
      information networks, and organized continuing education.

PMID- 8302104
TI  - Strategies to increase mammography utilization.
AB  - This study compared the effects of theoretically driven interventions on
      compliance with mammography utilization. A 2 x 2 factorial design yielded four
      groups: a control group, a belief intervention group, an informational
      intervention group, and a belief/informational intervention group. A probability
      sample of 301 women, age 35 and older, without a history of breast cancer were
      randomly assigned to groups. Subjects in the intervention groups received
      individually tailored messages to alter beliefs or provider information related
      to mammography screening. Belief messages were developed from Health Belief Model
      constructs. Belief interventions significantly influenced all belief variables
      except perceived susceptibility in the desired direction. Women in the
      belief/informational intervention group were almost four times more likely than
      those in the control group to comply with mammography recommendations in the year
      following intervention (odds ratio = 3.75). In addition, belief variables and
      intervention significantly predicted mammography compliance 1 year
      postintervention.

PMID- 8302105
TI  - The relationship of provider organizational status and erythropoietin dosing in
      end stage renal disease patients.
AB  - Controversy exists as to whether provider organizational characteristics such as
      profit status and setting are associated with the content of medical care or
      efficiency with which care is rendered. Following FDA approval of human
      recombinant erythropoietin (EPO) for use in clinical practice, Medicare approved
      coverage for beneficiaries in its end stage renal disease program and established
      a fixed payment per dose. Because cost of EPO administration varied positively
      with dose, providers could realize larger profit with prescription of smaller
      doses. We used Medicare claims data to assess EPO use by renal dialysis providers
      one year after FDA approval (June 1990) as a function of provider ownership (for
      profit, not-for-profit, government agency) and setting (hospital-based, free
      standing). Mean dose of EPO was 236 units greater (P = 0.0001) for not-for-profit
      freestanding facilities, 593 units greater (P = 0.0001) for government
      facilities, and 555 units greater for not-for-profit hospitals (P = 0.0001) than
      among for-profit freestanding providers. With fixed payment per dose of EPO, for
      profit, freestanding providers prescribed EPO more often and administered smaller
      doses than not-for-profit or government providers, behavior that is consistent
      with profit maximization.

PMID- 8302106
TI  - Emigrant physicians evaluate the health care system of the former Soviet Union.
AB  - This study is a retrospective evaluation of the Soviet health care system by
      1,100 Jewish physicians who immigrated to Israel in 1990, but were professionally
      active in the former Soviet Union before and during the Gorbachev era. Medical
      education and the process of specialization; gender differences within the
      medical profession; sources of work satisfaction and dissatisfaction; self
      evaluations of professional behavior; and assessments of patient behavior are
      included in this empirical study. Although high levels of dissatisfaction were
      found regarding instrumental aspects of work, the physicians reported high levels
      of satisfaction with their relationships with colleagues and patients. The recent
      emigrants assessed their own role behavior and that of their patients more
      critically than did physicians who left the Soviet Union in 1972, and who
      answered identical questions in 1975. Among the recent emigrants, men, older
      physicians, and those with higher status within the profession tended to be more
      satisfied with their work and less critical about their own and their patients'
      behavior than their female, younger and lower status colleagues. The subjective
      perceptions of former "insiders," which complement the reports that have appeared
      in recent years in the medical literature, are discussed in terms of the impact
      of glasnost and perestroika on reporting behavior and on the real deterioration
      that occurred in the health care system of the former Soviet Union.

PMID- 8302107
TI  - In search of power and significance: issues in the design and analysis of
      stochastic cost-effectiveness studies in health care.
AB  - Application of techniques such as cost-effectiveness analysis (CEA) is growing
      rapidly in health care. There are two general approaches to analysis:
      deterministic models based upon assumptions and secondary analysis of
      retrospective data, and prospective stochastic analyses in which the design of a
      clinical experiment such as randomised controlled trial is adapted to collect
      patient-specific data on costs and effects. An important methodological
      difference between these two approaches is in the quantification and analysis of
      uncertainty. Whereas the traditional CEA model utilizes sensitivity analysis, the
      mean-variance data on costs and effects from a prospective trial presents the
      opportunity to analyze cost-effectiveness using conventional inferential
      statistical methods. In this study we explored some of the implications of moving
      economic appraisal away from deterministic models and toward the experimental
      paradigm. Our specific focus was on the feasibility and desirability of
      constructing statistical tests of economic hypotheses and estimation of cost
      effectiveness ratios with associated 95% confidence intervals. We show how
      relevant variances can be estimated for this task and discuss the implications
      for the design and analysis of prospective economic studies.

PMID- 8302108
TI  - Ownership of clinical laboratories by referring physicians: effects on
      utilization, charges, and profitability.

PMID- 8302109
TI  - The relationships between the dimensions of health care quality and price: the
      case of eye care.

PMID- 8302110
TI  - Stability and responsiveness of utility measures.

PMID- 8302111
TI  - Advance directives: can patients' stated treatment choices be used to infer
      unstated choices?
AB  - Advance directives have been widely endorsed as a method to match medical
      interventions to patients' preferences. However, applying advance directives to
      unspecified future decisions may be problematic. We wondered how well scenario
      based treatment choices in advance directives can be used to infer other choices
      specified by the same patients. We asked 495 out-patients from the Massachusetts
      General Hospital to state 11 treatment choices in each of four illness scenarios.
      We calculated likelihood ratios (LRs) to see how well one choice could predict
      another. Predictions within a given scenario were strong and followed a pattern
      that reflected the invasiveness of the treatment. Thus, decline of antibiotics
      predicted decline of major surgery, in the same scenario (LR 36.0-108.3).
      Requests for major surgery strongly predicted requests for antibiotics (LR 90.4
      244.1). Requests for major surgery and decline of antibiotics were the two most
      predictive preferences; more traditionally considered decisions about
      cardiopulmonary resuscitation and mechanical ventilation ranged from the third to
      ninth most predictive among the 11 interventions. Predictions between scenarios
      were weaker, but still potentially useful, and followed a pattern that reflected
      the prognoses of the scenarios. Declining treatment in the best prognosis
      scenario (coma-with-a-chance) predicted declining the same treatment in other
      scenarios with LRs of 2.5-6.1. Requests for treatment in the worst prognosis
      scenario (dementia-with-terminal-illness) predicted the same request in the other
      scenarios with LRs of 5.2-30.5. These data suggest that patients' advance
      scenario-based treatment choices can provide potentially useful information to
      apply to unspecified decisions if inferences follow considerations of prognosis
      and treatment invasiveness. For maximal predictive power, treatment directives
      should use a range of illness scenarios and include choices, among several
      others, on antibiotic use and major surgery.

PMID- 8302112
TI  - Mucosal melanoma of the head and neck: the impact of local control on survival.
AB  - The management for mucosal melanoma of the head and neck is controversial in view
      of the poor prognosis. Thirty-five patients seen from 1955 to 1991 were analyzed
      retrospectively. Almost all (34/35) presented with localized disease. Primary
      treatments included radical surgery (15), local resection (11), radiation therapy
      (6), or systemic treatment (2). While the rate of local recurrence was high
      (27/34), only 5 patients developed distant disease before local relapse.
      Furthermore, only 5/21 achieved successful local salvage. Patients with their
      disease controlled locally had significantly longer survival than those with
      persistent local disease (P = .0001). The 5-year disease-specific survival was
      45%. The authors conclude that mucosal melanoma of the head and neck is not
      necessarily incurable. When local control is achieved, survival rate is
      significantly improved. Aggressive local treatments should be initiated at
      presentation of this disease.

PMID- 8302113
TI  - Cloning and sequencing of genomic DNA extracted from archival human temporal bone
      sections.
AB  - Cloning techniques allow the engineering and production of highly purified DNA.
      Further advances in molecular biology have provided the means to identify DNA
      sequences in a rapid fashion. Sequencing methods can identify mutations,
      deletions, polymorphisms, or confirm a known genetic sequence. The use of these
      techniques in clinical medicine has made it possible to accurately diagnose
      infectious diseases and determine the molecular etiology of many genetic
      disorders and malignancies. In this study, DNA extracted from archival, celloidin
      embedded temporal bone sections has been cloned and sequenced using these
      techniques. We amplified, cloned, and sequenced varicella-zoster viral DNA
      extracted from archival temporal bone sections from patients who had herpes
      zoster oticus. The application of cloning and sequencing techniques to DNA
      extracted from archival temporal bones provides the methodology to study temporal
      bone pathology at the molecular level.

PMID- 8302114
TI  - Juxtaposition lipoma to the mastoid seventh nerve.
AB  - The precise embryological source for fat in juxtaposition to the vertical portion
      of the seventh nerve in the mastoid is unknown. Seventeen percent of 240 temporal
      bones disclosed various amounts of fat adjacent to this portion of the nerve.
      Shiny areas of fat granules are occasionally seen around, and perhaps at first
      glance mistaken for, the seventh nerve during mastoid surgery. The radiographic
      appearance of fat in this area has not been described. Bilateral 1-cm ovoid
      images were interpreted in a 16-year-old girl as seventh nerve neuromas or
      perhaps hemangiomas, but were surgically proven to be a lipoma in the only ear
      operated on. Lipoma should be considered in the differential diagnosis for a mass
      in this location which demonstrates increased T1 signal, progressive decreased
      signal on T2-weighted images, and has signal intensity isodense with that of fat.

PMID- 8302115
TI  - The horizontal vestibulo-ocular reflex gain during active and passive high
      frequency head movements.
AB  - Patients with bilateral peripheral vestibular loss complain of varying degrees of
      oscillopsia and balance difficulties. Some are able to engage in sporting
      activities while others are completely disabled. An assumption that other inputs
      are available to the vestibulo-ocular reflex (VOR) enabling it to achieve some
      degree of visual stability during high-frequency head movement is reasonable. In
      this study, the gain of the horizontal vestibulo-ocular reflex in 10 healthy
      subjects was examined during active high-frequency head-on-body rotation (head
      free), and compared to high-frequency passive whole-body rotation (head fixed). A
      statistical difference in the gain (P < .002) was noted for all frequencies
      between the two groups. In those individuals undergoing passive whole-body high
      frequency movements, the gain was observed to rise (above unity) with increasing
      frequency of rotation, while the gain during active head-on-body rotation
      remained close to 1.

PMID- 8302116
TI  - Laryngeal verrucous carcinoma: a clinicopathologic study and detection of human
      papillomavirus using polymerase chain reaction.
AB  - Laryngeal verrucous carcinoma (LVC) is a rare, well-differentiated variant of
      squamous carcinoma with a low malignant potential. Human papillomavirus (HPV)-16
      DNA has been identified in a small number of LVC and an etiologic relationship
      has been suggested. A correlative clinical and molecular pathological study was
      performed in order to determine the prevalence and typing of HPV DNA in LVC.
      Possible associations between patient and tumor subsets, and the presence of HPV
      DNA were also investigated. Formalin-fixed, paraffin-embedded tissue samples from
      29 patients with LVC were examined by polymerase chain reaction (PCR) using DNA
      primers specific for HPV types 6b/11, 16, and 18. Overall, HPV DNA was detected
      in 13 (45%) of the cases. Of these, HPV-16 DNA, HPV-18 DNA, and both HPV-16 DNA
      and HPV-18 DNA were detected in 4 (14% overall; 31% of positive cases), 4, and 5
      (17% overall; 38% of positive cases), respectively. HPV-6b/11 DNA was not
      detected in any LVCs. In 16 cases, no HPV DNA was detected. There was a trend
      toward HPV DNA detection in higher stage tumors. HPV DNA detection was unrelated
      to patient age, tumor site, or radiotherapeutic responsiveness. The detection of
      HPV DNA in 45% of LVCs suggests an association between the presence of HPV-16 DNA
      and HPV-18 DNA, and some LVCs.

PMID- 8302117
TI  - The turbulent noise ratio: an estimation of noise power of the breathy voice
      using PARCOR analysis.
AB  - The degree of turbulent noise in the breathy voice of 25 patients with incomplete
      glottal closure was determined by PARCOR (PARtial autoCORrelation) analysis. From
      10,000 acoustic data points, 44 PARCOR coefficients were calculated to form the
      residue wave which is representative of the glottal source. The power difference
      between the residue wave and the original acoustic wave was calculated in order
      to define a new measurement of acoustic power termed the turbulent noise ratio
      (TNR). The 25 patients were studied before and after Isshiki thyroplasty type I
      (IttI). The TNR became smaller in 24 of these patients following IttI, and
      corresponded closely with acoustic (Fukazawa's Br-Index), aerodynamic (Isshiki's
      AC/DC ratio), mean airflow rate during phonation, and videolaryngostroboscopic
      findings. Data affirm that the TNR accurately reflects the degree of turbulent
      noise at the glottal source.

PMID- 8302118
TI  - The radiographic incidence of chronic sinus disease in the pediatric population.
AB  - The otolaryngologist is frequently consulted for paranasal sinus disease which
      has been identified as an incidental finding on computed tomography (CT) in
      children. The significance of such a finding is difficult to interpret without
      prior knowledge of the actual incidence of chronic sinus mucosal hypertrophy in
      the general pediatric population. In this study of pediatric CT scans from busy
      otolaryngology and ophthalmology clinics, the radiographic incidence of sinus
      disease in the general pediatric population is estimated. One hundred forty-two
      CT scans of the orbits and temporal bones obtained over an 18-month period were
      reviewed. Fifty-eight (41%) scans showed some mucosal thickening or opacification
      in at least one sinus. When patients were stratified by age, or by the presence
      or absence of chronic otitis media or respiratory tract disease, exclusive of
      clinical sinusitis, there was no statistical difference between groups. The
      authors conclude that the asymptomatic child with an incidental paranasal sinus
      finding on CT scan need not be worked up further unless clinical symptoms and
      signs are elicited.

PMID- 8302119
TI  - Cochlear implantation in young children: histological studies on head growth,
      leadwire design, and electrode fixation in the monkey model.
AB  - For safe cochlear implantation in children under 2 years of age, the implant
      assembly must not adversely affect adjacent tissues or compromise head growth.
      Furthermore, growth changes and tissue responses should not impair the function
      of the device. Dummy receiver-stimulators, interconnect plugs, and leadwire
      lengthening systems were implanted for periods of 36 months in the young monkey
      to effectively model the implantation of the young child. The results show that
      implanting a receiver-stimulator package has no adverse effects on skull growth
      or the underlying central nervous system. The system for fixing the electrode at
      the fossa incudis proved effective. There was marked osteoneogenesis in the
      mastoid cavity, resulting in the fixation of the leadwire outside the cochlea.
      This study provides evidence for the safety of cochlear implantation in young
      subjects.

PMID- 8302120
TI  - Sensorineural hearing loss from quinolinic acid: a neurotoxin in middle ear
      effusions.
AB  - Quinolinic acid (QUIN) is an endogenous metabolite that exerts a neurotoxic
      effect by binding to specific neuronal receptors. Studies involving a broad
      spectrum of infectious and inflammatory central nervous system diseases have
      suggested a role for QUIN in causing neuronal injury. Since there is evidence for
      presence of the QUIN receptor in mammalian cochleas, QUIN was measured in middle
      ear effusions (MEEs). Gas chromatography/mass spectrometry detected QUIN in each
      of 65 diluted human MEEs, with a mean of 482 +/- 75 (SEM) nmol/L and a range from
      15 to 2667 nmol/L. QUIN was also detected in each of 197 chinchilla MEEs from
      five different models of otitis media, with a mean of 10.6 +/- 1.3 (SEM) mumol/L
      and a range from 0.23 to 146.0 mumol/L (corrected for dilution). To determine
      whether QUIN causes sensorineural hearing loss (SNHL), QUIN solutions were placed
      on round window membranes (RWM) for 20 to 240 minutes, in 20 chinchillas. SNHL
      was detected by electrocochleography in QUIN-exposed animals, but not in saline
      controls. We conclude that QUIN is present in MEEs and that QUIN in the middle
      ear has the potential to cross the RWM and cause sensorineural hearing loss,
      possibly by binding to specific neuronal receptors in mammalian cochleas.

PMID- 8302121
TI  - Auditory evoked potentials at 40 Hz (SSR40Hz) in post-trauma coma patients.
AB  - The authors evaluated auditory evoked steady state rest potentials at 40 Hz
      (SSR40Hz) in 21 post-trauma coma patients and compared their predictive value for
      prognosis of survival and quality of life with the results of the
      electroencephalogram (EEG), the computed tomography (CT) scan, and the Glasgow
      Coma Scale. SSR40Hz potentials recorded immediately after trauma had a maximum
      (100%) sensibility and specificity for a fetal prognosis and a high value for
      life prognosis. Consequently they appear to be a useful parameter for deciding on
      organ explant procedures. The EEG was more reliable in predicting a quality of
      life prognosis.

PMID- 8302122
TI  - Pathogenesis of peritonsillar abscess.
AB  - The pathogenesis of peritonsillar abscess is described in textbooks as being a
      direct communication and progression of acute exudative tonsillitis. Little study
      has been done on the true etiology and pathogenesis of peritonsillar abscess.
      This paper focuses on the pathogenesis of peritonsillar abscess. A group of
      salivary glands (Weber's glands) proven to be located in the supratonsillar space
      have been shown to be implicated in the pathogenesis of peritonsillar abscess. A
      review of peritonsillar abscess has been undertaken, and evidence has been
      presented to support the premise that the true cause for peritonsillar abscess is
      not necessarily an extension of an acute exudative tonsillitis, but an abscess
      formation of Weber's salivary glands in the supratonsillar fossa.

PMID- 8302123
TI  - Cytokines in experimental otitis media with effusion.
AB  - Studies in the authors' laboratory have recently demonstrated the presence of
      potent inflammatory cytokines such as interleukin-1 beta (IL-1 beta), interleukin
      6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) in human middle ear
      effusions. The clinical significance of this finding has not been fully
      elucidated because of the limitations of human studies. We hypothesized that the
      chinchilla model of otitis media may be an appropriate system with which to study
      the role of cytokines in otitis media with effusion. To begin to investigate this
      possibility, 30 chinchillas underwent surgical blockage of the eustachian tube
      (ET) to promote effusion development. After 2 weeks, examination by otoscopy
      demonstrated 27 ears to have developed an effusion. Next, all middle ear clefts,
      in random manner, were either injected with heat-killed Streptococcus pneumoniae
      1 x 10(6) in 0.1 mL normal saline, injected with 0.1 mL normal saline alone, or
      received no injection at all. Middle ear effusions were obtained and analyzed for
      IL-1 beta and TNF alpha by enzyme-linked immunosorbent assay (ELISA). This study
      demonstrated a significant correlation between IL-1 beta and the presence of an
      effusion (P < .001). Additionally, increased TNF alpha levels correlated with
      bacterial component presence (P < .001), i.e., mean TNF alpha level was 108,
      10.8, and 0 pg/mL in bacteria, normal saline, and noninjected ears, respectively.
      These findings would suggest that cytokine expression may relate to specific
      pathological conditions and that the chinchilla model for otitis media with
      effusion (OME) could be used to further explore the role of cytokines in OME.

PMID- 8302124
TI  - Reserpine inhibits the NaK ATPase activity of the stria vascularis in the
      cochlea.
AB  - The function of the stria vascularis in the cochlea is believed to be the
      production of endolymph. The mechanisms that maintain or control the function of
      the stria vascularis, however, remain unclear. In the present study, the effects
      of one-shot reserpine administration on the NaK ATPase activity of the stria
      vascularis in guinea pigs were investigated. NaK ATPase activity was shown to be
      completely inhibited 3 to 20 days after reserpinization, and was detectable again
      60 days after reserpinization. As reserpine is an adrenergic neuron blocker,
      these results suggest that catecholamines may play an essential role in the
      maintenance or control of NaK ATPase activity, and that the stria vascularis may
      be one of the target organs of catecholamines.

PMID- 8302125
TI  - Testing biomechanical strength of repairs for the mandibular angle fracture.
AB  - A biomechanical model using polystyrene mandibles with simple angle fractures was
      developed to evaluate the structural strength of a variety of commonly used plate
      repairs. The model standardized the fracture location, load site, plate location,
      and site of deformation measurement. The only variables in the study were the
      nine different reconstruction types tested. Precise measurements of the
      deformation under load demonstrated statistically significant intra-group
      reproducibility for each repair. Data support previous clinical and experimental
      studies demonstrating the superiority of a two-plate system applied to the
      tension and compression regions of the mandible when compared to single-plate
      repairs using either noncompression (bridging) or eccentric dynamic compression
      plates.

PMID- 8302126
TI  - Reflex laryngospasm induced by stimulation of distal esophageal afferents.
AB  - Distal esophageal sensory nerves were stimulated in 17 anesthetized dogs divided
      into three age groups to determine the laryngeal, cardiovascular, and respiratory
      effects. Group I puppies were 5 to 6 weeks of age, group II puppies were 8 to 19
      weeks of age, and group III animals were adult dogs. Marked laryngeal adductor
      activity and laryngospasm were observed in group II puppies, while no or minimal
      laryngeal adduction was seen in younger puppies and adult dogs. Mean arterial
      pressure and heart rate increased significantly in groups II and III (P < .005)
      but remained unchanged in group I animals (P > .4). This response is distinctly
      different from the laryngeal chemoreflex because central apnea, hypotension, and
      bradycardia were absent. The afferent limb of the response is mediated by the
      vagus nerve as bilateral transthoracic truncal vagotomy eliminated the reflex.
      The laryngeal response observed following stimulation of distal esophageal
      afferent fibers may be important in the mechanism of apparent life-threatening
      events (ALTEs) and the sudden infant death syndrome (SIDS) associated with
      gastroesophageal reflux disease.

PMID- 8302127
TI  - Tongue reinnervation by hypoglossal-lingual nerve transfer.
AB  - The morbidity associated with total glossectomy for treatment of base of tongue
      carcinomas provides the impetus to investigate techniques to salvage the
      uninvolved normal anterior tongue. This report describes a method of
      reinnervation of the anterior tongue using a hypoglossal-lingual transfer. In
      Cynomolgus monkeys, unilateral transfers with and without a subsequent muscle
      fillet resulted in reinnervation from the base to the tip of the tongue. It is
      proposed that hypoglossal-lingual nerve transfers be considered to allow sparing
      and return of function to the anterior tongue in conjunction with a resection of
      the tongue base. Additional experiments confirmed that the base of the tongue,
      like other midline muscles, has bilateral and separate innervation. The presence
      of a physiological lingual-hypoglossal reflex in the normal animal was
      documented.

PMID- 8302128
TI  - High relative risk of a second pulmonary cancer in patients affected by laryngeal
      cancer: differences by specific site of occurrence and lung cancer histotype.
AB  - The frequency of a second primary lung tumor in patients affected by laryngeal
      cancer has been evaluated on the basis of 128,532 biopsies and 27,753 autopsies
      carried out from January 1, 1979 through December 31, 1988. Among these cases,
      432 laryngeal cancers and 44 synchronous or metachronous pulmonary cancers have
      been detected (7 during life, 37 at autopsy). The highest risk of developing a
      lung tumor has been evidenced in patients affected by supraglottic cancer during
      the first 2 years of follow-up (relative risk [RR]: 32.56 for supraglottic
      patients versus 5.55 for glottic patients). This is particularly true of patients
      affected by multicentric supraglottic tumors (RR: 62.5). A significant
      hyperfrequency of undifferentiated lung cancers also has been noted in
      supraglottic patients (RR: 45.45 for supraglottic versus 14.28 for glottic
      patients). The information provided by autopsy allows for a more realistic and
      detailed outlining of the issue of tumor multiplicity, stressing the importance
      of strict preventive and follow-up protocols.

PMID- 8302129
TI  - Ventilation by metal suction catheter during tracheal laser surgery performed on
      a premature infant.

PMID- 8302130
TI  - Intraoperative monitoring of the facial nerve: an aid in the management of
      parotid gland recurrent pleomorphic adenomas.

PMID- 8302131
TI  - A new method for tracheoesophageal puncture under topical anesthesia.

PMID- 8302132
TI  - [Reference values for FVC, FEV1 and FEF25-75% in school children].
AB  - Reference values for FVC, FEV1 and FEF25-75% have been developed on a sample of
      2500 healthy school-children (nonsmokers) from Split, ranging in age from 6 to 18
      years. We measured respiratory parameters (FVC, FEV1 and FEF25-75%) in a standing
      position, statistically analysed the results and presented them tabularly with
      regard to age, standing and sitting height and body weight. The results revealed
      a high correlation between FVC and FEV1 with respect to age, standing and sitting
      height and body weight. There was no significant difference between respiratory
      parameters and the two measured positions (standing and sitting positions). A
      statistically significant difference was noted in the ventilatory parameters of
      the children (FVC, FEV1) between the boys and girls. Regression analysis was
      performed for all three respiratory parameters (FVC, FEV1 and FEF25-75%) vs age
      and height, separately for boys and girls. Nomograms for predicting respiratory
      parameters for boys and girls from the Dalmatian region were also constructed in
      order to enable better future epidemiologic studies for early detection of
      ventilatory impairment in school-children.

PMID- 8302134
TI  - [Auditory evoked potentials in alcoholics].
AB  - In this paper, auditory brain stem potentials in the group of 26 alcoholics were
      studied and a significantly delayed latencies of the peaks II through V as
      compared to the healthy control subjects were found. In addition, a statistically
      significant prolongation of brain stem transmission time (BTT) in alcoholics was
      observed. The study also suggests the possibility of monitoring the level of
      pathohistological changes of the central auditory pathway caused by excessive
      alcohol consumption.

PMID- 8302133
TI  - [The combined immunoenzyme test: anti-HIV-1 and -2 and anti-HTLV-1 in the
      detection of donors with retrovirus infections].
AB  - Serums of whole blood donors, plasma donors, hemophiliacs, persons with risks
      behavior and normal population simultaneously were tested for markers of
      infectious diseases, anti-HIV-1 with Plivazim and anti-HIV-1/2 and anti-HTLV-1/2
      with Roche Retrovirus EIA. The positive results were confirmed by
      immunofluorescence assay and Western blot. Nonspecific reactive serums were
      detected by Roche Retrovirus EIA and by Plivazim EIA, but there was no
      significant difference in the frequence of reactive results. Roche Retrovirus EIA
      test had specificity of 99.16% and sensibility of 97.56% as compared to Plivazim.
      Simultaneous testing of donors with a combined test for anti-HIV-1/2 and anti
      HTLV-1 is equally reliable as testing with only anti-HIV-1.

PMID- 8302135
TI  - [Personal experience in the care of open fractures using external fixation during
      the hostilities in Osijek and surrounding region].
AB  - In the period of aggression of the Federal Army and Serbian paramilitary forces
      on the City of Osijek and its surrounding, beginning in the summer of 1991, 4036
      wounded were treated at the Department of Surgery, Osijek General Hospital.
      Extremity injuries were documented in 3889 patients, including 959 bone
      fractures. The majority of patients had wounds caused by highly destructive
      explosives filled with metal fragments of different shapes and dimensions, and
      having sharp and uneven edges. One hundred and forty wounded were treated by
      external fixators. In 102 patients this mode of fixation was applied for gun- and
      explosive-related long bone fractures of the lower extremities. External fixator
      for the upper and forearm fractures was used in 38 cases. During this period,
      different types of external fixators were used and experience in this work has
      been gained. Stability of both open and unstable bone fractures of the
      extremities, caused by explosive devices, has been obtained by the external
      fixation mostly in one plane, regardless of the type of external fixator used.
      The advantages of use of external fixators of the types Instrumentarija Zagreb 1
      and 2 for the treatment of long bone fractures has been emphasized as well as the
      possibility of the subsequent corrections owing to the technical construction of
      the bone spike. The usefulness of the longitudinal bar of the AO/ASIF fixator for
      the healing of fractures of the upper leg with subsequent callus formation is
      also stressed. The same stability has been achieved by the CMC fixator. The
      external fixators of a type Zagreb 2 have been a satisfactory treatment for
      forearm fractures as well.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302136
TI  - [Acute renal failure in heart transplantation].
AB  - In this study the incidence and the development of acute renal failure (ARF) in
      heart transplant recipients is presented. Among the thirteen heart transplant
      recipients eight of them developed oliguric or nonoliguric ARF. Besides the known
      factors such as actual condition of the patient, kidney function, peri and post
      operative compromised circulation, our results demonstrate the significance of
      postoperative cyclosporin concentration in combination with the use of other
      drugs. The results also show the importance of the way cyclosporin has been
      administrated. The parenteral route of appliance is connected with the greater
      risk of higher drug concentration in the plasma than the peroral one. In
      connection with this is the higher incidence of adverse reactions to cyclosporin
      given parenterally. In addition to ranitidine and captopril, which have been
      mentioned earlier, the findings of our study indicate that greater attention has
      to be paid to the treatment with ketoconazol given in combination with
      cyclosporin, since it results in decreased cyclosporin clearance. Other
      nephrotoxic drugs like amphotericin also increase the possibility of renal
      lesions. The incidence of acute renal failure in this group of patients is high.
      Our data suggest that the reasons for the development of ARF are multifactorial.
      These data further suggest that a reasonable way to solve nonoliguric form of
      acute renal failure is to maintain the "internal balance" and that it is not
      necessary to perform extracorporeal elimination of nitrogen substances, if there
      are no additional complications (i.e. gastrointestinal bleeding).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8302137
TI  - [How much do we understand about pharmacotherapy of cardiac arrhythmias?].
AB  - By an anonymous, multiple-choice questionnaire assessed was the knowledge of
      cardiac electrophysiology and mechanism of action of some antiarrhythmic drugs
      among the staff members of a department of medicine from a large regional
      hospital. The overall results were disappointing (over 55 per cent of inaccurate
      answers), but improved after 3 months (less than 30 per cent). It is concluded
      that such a polling increases the level of awareness about target problem
      (cardiac arrhythmia management in the actual case) and improves the performance
      of health professionals.

PMID- 8302138
TI  - [Direct communication of the pulmonary artery with the left atrium].
AB  - A rare communication between the right pulmonary artery and the left atrium in a
      3.5-year-old girl is described. Cyanosis of a central type and a continuous
      murmur over the heart were presenting symptoms. Echocardiography revealed only
      excessive pulsations of the pulmonary artery, while catheterization pointed to an
      abnormal aneurysmal communication between the right pulmonary artery and the left
      atrium. At this point the O2 saturation was at the level of the left atrium. The
      communication was clinically classified as a type IV according to Nelson. After
      an unsuccessful attempt through a right thoracotomy, the ligature of this fistula
      has been performed in the second attempt through a median sternotomy and under
      complete extracorporeal circulation. Clinical course and review of literature of
      this rare anomaly of the heart are being presented.

PMID- 8302139
TI  - [Trichorhinophalangeal syndrome].
AB  - A girl with tricho-rhino-phalangeal syndrome is described. Besides clinical and
      radiologic symptoms of type I of this syndrome (short stature, pear-shaped nose,
      prominent and elongated philtrum, small carious teeth, thin and sparse hair,
      badly shaped laterally protruding ears, deep voice, cone-shaped phalangeal
      epiphyses as well as shortening of metacarpal and metatarsal bones) the patient
      exhibits a group of abnormalities characteristic for type II (broad nasal bridge,
      thicker septum, laterally postured nostrils, heavier eyebrows, mild deafness and
      epilepsy). The girl also has the symptoms of primary hypothyroidism because of
      the ectopic thyroid gland, the first recorded instance up to now, so it is
      probably a coincidence.

PMID- 8302140
TI  - [The laryngeal mask--news in orthopedic anesthesia].
AB  - The laryngeal mask airway (LMA) was first used at the Department of Orthopedics,
      School of Medicine, University of Zagreb on May 8, 1991. Two hundred and three
      patients were undergoing elective orthopedic surgery during the first year of the
      LMA use. A size-3 mask was used for women and children weighing over 25 kg (55
      lbs) and a size-4 mask for men. Research has been undertaken in 12 patients aged
      between 30-73 years scheduled for total hip replacement. Blood pressure, heart
      rate and hemoglobin oxygen saturation were continuously monitored with a
      noninvasive method. No signs of cardiovascular disorders were noticed 1-min
      before and 3-min after insertion. Only 2 (16.6%) patients, who suffered no
      complications, had ventilating pressure higher than 20 cm H2O. The LMA proved to
      be very useful in anesthesia where endotracheal intubation was difficult or
      almost impossible. Of 12 examinees, 3 with severe rheumatoid arthritis and 2 with
      ankylosing spondylitis were successfully anesthetized with the LMA. Awakening
      from anesthesia was very pleasant. There were no serious complications in terms
      of laryngo- or bronchospasm, aspiration or insufflation of the stomach. The LMA
      has been found to be very helpful in solving problems of anesthesia in orthopedic
      patients. A set of laryngeal mask airways should be an integral part of every
      anesthetic equipment.

PMID- 8302142
TI  - [Passive smoking--(un)recognized effects on the respiratory system].
AB  - Passive smokers are exposed to a quantitatively smaller but qualitatively
      different smoke than active smokers. Clinical and epidemiological investigations
      indicate that allergic and nonallergic subjects are susceptible to tobacco smoke.
      The most frequent symptoms are eye irritation and blinking, nasal and throat
      irritation, nausea and headache. Acute effects on respiratory system are
      manifested by increase of airway resistance and decrease of airway specific
      conductance. Chronic effects include deterioration of pulmonary function,
      exacerbation of allergy, chronic pulmonary diseases, angina pectoris and increase
      of relative risk of lung cancer. Children are sensitive to tobacco smoke even
      before birth and exposure during the first year of life increases the risk of
      respiratory disease. Passive smoking at workplace is recognized as a cause of
      occupational respiratory diseases and the tollerable concentration of cigarette
      smoke is suggested for 8-hour exposure of healthy workers.

PMID- 8302141
TI  - [Thrombolytic therapy in acute myocardial infarct in 1992].
AB  - The management of acute myocardial infarction has dramatically changed in the
      last decade. The conservative approach with bed rest, oxygen therapy, pain relief
      and prevention of complications--the former cornerstones of the treatment of
      acute myocardial infarction--are now being replaced with new, more aggressive
      forms of therapy, including early administration of thrombolytic agents. With the
      more than 100,000 patients studied in various clinical trials in the different
      parts of the world, the use of thrombolytic therapy is probably the most
      thoroughly studied medical intervention in human medical history. The results of
      these trials undoubtedly showed that thrombolytic therapy had a major impact on
      reducing mortality and preserving left ventricular function in patients with
      acute myocardial infarction. The purpose of this article is to review current new
      information on thrombogenesis and thrombolysis, the indications and
      contraindications of thrombolytic therapy, comparisons between different
      thrombolytic agents and the role of adjuvant antithrombotic therapy.

PMID- 8302143
TI  - [Does one-fifth of our population really die from smoking?].
AB  - Scientific research has confined the causal connection between tobacco smoking,
      i. e. inhaling of tobacco smoke and malignant and other disease. As reported by
      WHO experts, tobacco smoke is one of the main causes of death from lung cancer in
      90-95% cases, in other types of cancer in 45-50%, lung obstructive diseases,
      chronic bronchitis and emphysema in 75-80% and cardiovascular diseases in 20-25%.
      According to the above given percentage, in the Republic of Croatia average of
      over 10,000 persons die yearly as a consequence of tobacco smoking out of which
      3,000 on the territory of Zagreb, or 20% of the total number of dead. The
      Committee for deliberating Zagreb from smoking has initiated the intersection
      approach to the control of smoking as a part of the "Healthy City" Movement. As a
      conclusion, all health institutions and professional associations of health
      workers are called to make public assessment of the harm smoking can do to the
      health of our citizens and take necessary legal measures for its control.

PMID- 8302144
TI  - [Automatic reprocessing and multiple reuse of dialyzers--experience at the
      Dialysis Center at the Sestre Milosrdnice Clinical Hospital in Zagreb].

PMID- 8302146
TI  - [The hemodynamic and ventilatory effects between Trendelenburg and reverse
      Trendelenburg position during laparoscopy with CO2-insufflation].
AB  - Thirty ASA class I female patients underwent gynecologic pelvioscopy and
      laparoscopic cholecystectomy were included in this study. All of them received
      general anesthesia and certain volume of CO2 pneumoperitoneum. We evaluated the
      effect of positioning (Trendelenburg as group I and reverse Trendelenburg as
      group II) on hemodynamic parameters and ventilation. The hemodynamic parameters,
      ventilation, and arterial blood gas were determined at the following stages: (1)
      after 10 minutes of normoventilation and before CO2 pneumoperitoneum (as
      control), (2) 5 minutes after CO2 pneumoperitoneum and positioning, (3) 25
      minutes after positioning, (4) 50 minutes after positioning, (5) 10 minutes after
      resumption of supine position and decompression of abdomen. Arterial blood
      pressure, heart rate, minute volume, end-tidal CO2, oxygen saturation and blood
      gas analysis were taken during normoventilation. We found that there was no
      statistical difference between either group in respect to hemodynamic parameters.
      For the ventilation, both groups had appropriate SpO2 during the period of CO2
      pneumoperitoneum, but PaCO2 was significantly increased in group I 25 min after
      CO2 pneumoperitoneum and Trendelenburg positioning. Nonetheless, end-tidal CO2
      was not significantly increased. pH value and PaCO2 did respectively decrease and
      increase significantly in group I 50 min after Trendelenburg position. However,
      no change was found in end-tidal CO2. All data were not significantly different
      after resumption of supine position and decompression of abdomen. Conclusively,
      except that pH and PaCO2 had changed after a period of Trendelenburg positioning
      with CO2 pneumoperitoneum, the patients who underwent laparoscopic surgery with
      normoventilation have no hemodynamic and respiratory change.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8302145
TI  - Preliminary experience of using fixed dose of intravenous labetalol in surgical
      resection of pheochromocytoma.
AB  - Seven patients scheduled for resection of pheochromocytoma with loose
      preoperative control of their blood pressure were selected in our study. All the
      cases are impressed of pheochromocytoma that predominantly excrete
      norepinephrine. Anesthesia was induced with fentanyl, 2.5% sodium thiopental,
      valium and atracurium. Labetalol was used as antihypertensive agent and was given
      in repeated bolus (up to total dose of 2 mg/kg) intravenously before skin
      incision and no supplemental dosage was given later on. The anesthesia was
      maintained with nitrous oxide, oxygen, isoflurane and atracurium. Blood pressure,
      heart rate and arterial blood gas analysis were recorded. After giving
      intravenous labetalol, mean systolic blood pressure and heart rate declined by
      26.2% and 29.76% respectively when compared to preanesthetic values. Although
      bradycardia was noted after administration of labetalol, it seemed acceptable
      except for one patient who needed atropine right after receiving labetalol and
      another patient who needed levophed infusion after tumor removal. During tumor
      removal, the blood pressure of all patients was stable except one patient who
      needed sodium nitroprusside infusion together with labetalol to help control the
      elevated blood pressure. All the patients in our study had no sequela
      postoperatively. We concluded that total dose of labetalol (2 mg/kg) administered
      intravenously at the beginning of anesthesia was possible to control blood
      pressure during the resection of pheochromocytoma under general anesthesia even
      in the case of poor preoperative blood pressure control.

PMID- 8302147
TI  - [Comparison of intravenous alfentanil, fentanyl and epidural lidocaine for
      extracorporeal shock wave lithotripsy].
AB  - Due to the development of newer generation of lithotriptor, the anesthesia for
      extracorporeal shock wave lithotripsy (ESWL) was variable recently. To compare
      opioid analgesia with epidural lidocaine for their efficacy in pain control,
      hemodynamic changes, side effects and patient acceptance during ESWL, sixty
      unpremedicated patients undergoing elective ESWL for upper urinary calculi with
      second generation Dornier MFL 5000 nonimmersion lithotriptor were randomly
      assigned equally into one of the following managements: Group E: 1% epidural
      lidocaine with 1:200000 epinephrine; Group A: 15 micrograms/kg alfentanil
      initially and 7 micrograms/kg on demand intravenously; Group F: 4 micrograms/kg
      fentanyl initially and 2 micrograms/kg on demand intravenously. Significant
      hypotension and bradycardia occurred in Gp.E as compared to baseline value (p <
      0.05). Early respiratory depression was observed in both Gp. A and Gp. F, but Gp.
      A showed significantly shorter period (2 to 5 minutes) as compared to Gp.F (2 to
      15 minutes). Under the insufflation of oxygen by nasal cannula, mean PaCO2
      increased maximally to 50 mmHg, but no arterial oxygen desaturation (< 90%) was
      noted in Gp.A and Gp.F. The incidence of post-ESWL nausea was higher in Gp.F (p <
      0.05), shivering and delayed recovery time were the main disturbing problems in
      Gp.E (p < 0.01). Although five-point verbal pain scale was significantly higher
      in Gp.A and Gp.F (at 30 to 45 minutes during ESWL) as compared to Gp.E,
      acceptance among patients was high throughout the course. We conclude that
      different anesthetic plans should be determined on different lithotriptors
      settings and patient's physical condition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302148
TI  - The effect of high dose intravenous labetalol on plasma glucose during surgery.
AB  - As high dose intravenous labetalol was always used in performing deliberate
      hypotensive anesthesia and it was reported that small dose of intravenous
      labetalol would decrease the hyperglycemic response under surgical stress, high
      dose intravenous labetalol may theoretically causes more pronounced reduction in
      plasma glucose. 14 female cervical cancer patients (ASA physical status I-II)
      undergoing radical total hysterectomy were selected and randomly assigned into
      two groups (group A and group B). The anesthesia was induced with 2.5% sodium
      thiopental 4 mg/kg, atropine 0.3 mg, succinylcholine 1.5 mg/kg and fentanyl 3
      micrograms/kg intravenously. The anesthesia was maintained with isoflurane,
      nitrous oxide, oxygen and vecuronium under artificial controlled ventilation.
      Radial artery was cannulated for continuous blood pressure monitoring and blood
      sampling. The first sample was taken after intubation and before skin incision
      and the second sample was taken 5 minutes after skin incision in group A and
      after giving total dose of labetalol in group B, other blood samples were taken
      every 30 minutes thereafter. No labetalol was given in group A patients. In group
      B, labetalol (1.0-1.5 mg/Kg) was administrated intravenously in repeated bolus
      (10 mg/bolus) to achieve a mean blood pressure around 60 torr after skin
      incision. All the fluid administered intraoperatively was free of glucose. Any
      patients with blood loss greater than 1000 ml or having blood transfusion before
      the 5th samples (S5) were excluded because stored blood was rich of glucose. The
      result revealed that plasma glucose rose significantly in both groups but the
      rise occurred later in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302149
TI  - [Midazolam and Meperidine for colonoscopy].
AB  - We studied the sedative, analgesic and amnesic effects of intravenous midazolam
      and meperidine for colonoscopy, and also compared patient's satisfaction, changes
      of vital signs, safety and complications with intramuscular meperidine during the
      colonoscopy. Two hundred and ninety-nine patients undergoing physical check-up
      were randomized to receive intramuscular meperidine 50 mg and Hyoscine-N
      Butylbromide (buscopan) 20 mg (Group IM-MB, n = 57) or intravenous midazolam 0.05
      mg/kg, meperidine 1 mg/kg and buscopan 20 mg (Group IV-MMB, n = 242) before
      colonoscopy. All patients were closely observed and arterial oxygen saturations
      (SaO2) were monitored with pulse oximeter in Group IV-MMB. The demographic data
      of both groups were similar. There were significantly more severe pain responses
      (grimacing, moaning, shouting for pain, abdominal rigidity and body moving during
      colonoscopy) in Group IM-MB (51%) than in Group IV-MMB (13%) (p < 0.01). In
      immediate procedure recall after recovery from medications, 39% of Group IM-MB
      remembered severe pain during colonoscopy and only 3% of Group IV-MMB did (p <
      0.01). 92% of Group IV-MMB who felt satisfactory with the medications were
      significantly higher than 21% in Group IM-MB (p < 0.01). Both groups
      significantly increased in heart rate after the injection of medications (p <
      0.01). Group IM-MB increased 15 +/- 18% and Group IV-MMB 61 +/- 28% with
      significant difference between groups (p < 0.01). This might be caused by
      meperidine, buscopan, and relative hypovolemia of patients. There were
      significant decreases in SaO2 in Group IV-MMB, mean 4.5 +/- 1.7% (p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302150
TI  - Influence of epinephrine as an adjuvant to epidural morphine for postoperative
      analgesia.
AB  - The influence of the addition of epinephrine to epidural morphine on
      postoperative analgesia were investigated in 60 ASA physical status I or II
      patients aged average 45 yr. The treatments were given following lower extremity
      operation under epidural anesthesia with 2% Xylocaine solution in 20 mL. The
      subjects were randomly divided into 2 groups. Group A (n = 30) received 2 mg
      epidural morphine in 10 mL normal saline without epinephrine. Group B (n = 30)
      received 2 mg epidural morphine in 10 mL normal saline with epinephrine 0.1 mg
      (1:100,000, 10 micrograms/mL). Patients were assessed for quality and duration of
      postoperative analgesia, as well as the incidence and severity of side effects
      after epidural morphine administration. The addition of epinephrine to epidural
      morphine had significantly increased the quality and duration of analgesia. The
      side effects of pruritus, nausea, vomiting, and urinary retention were more
      intense after epinephrine-morphine administration. However, respiratory
      depression was not observed in both groups.

PMID- 8302151
TI  - Prolonged fasting in pediatric outpatients does not cause hypoglycemia.
AB  - Two hundred and thirty healthy children scheduled for receiving elective minor
      surgery were assigned into 4 different groups. Group I (small infant group)
      included 27 infants of age from 1 to 3 months (2.0 +/- 0.6 months), Group II
      (infant group) included 42 infants age from 3 to 12 months (7.4 +/- 2.8 months),
      Group III (pre-school children group) included 122 patients of age from 1 to 6
      years (3.1 +/- 1.4 years). The remained 39 cases of age older than 6-years-old
      (8.0 +/- 1.5 years) were collected in group IV (old children group). All studied
      children were starved for at least 4, 6, or 8 hours in infants, pre-school
      children, and old children group, respectively, pre-operatively. The fasting time
      and fasting blood glucose levels of the 4 groups were 6.7 +/- 1.4 hours and 109.0
      +/- 22.9 mg% in group I, 7.7 +/- 2.3 hours and 98.6 +/- 18.0 mg% in group II,
      10.4 +/- 2.9 hours and 96.9 +/- 24.7 mg% in group III, and 12.6 +/- 2.6 hours and
      95.7 +/- 20.5 mg% in group IV, respectively. No one in the 230 children had blood
      glucose less than 40 mg% even in 5 infants who were starved for 12 hours or more.
      Therefore, we concluded that preoperative starvation is well tolerated than the
      originally expected in the infants and children. The fasting time before
      anesthesia can be executed safely even though the operation schedule may not be
      right on time.

PMID- 8302152
TI  - Continuous succinylcholine infusion and phase II block in short surgical
      procedures.
AB  - The study was designed to observe continuous succinylcholine infusion and phase
      II block in short surgical procedures (duration < 90 min). The characteristics of
      neuromuscular blockade produced by continuous succinylcholine infusion were
      observed in 15 adult patients anesthetized with nitrous-oxide-isoflurane (0.7%
      end tidal concentration) and fentanyl, and were compared with the single-dose
      technique (n = 13) in recovery time. Ulnar nerve was stimulated supramaximally
      with repeated train-of-four (interval = 10 sec, frequency = 2 Hz) via surface
      electrodes at the wrist using an electromyographic monitor (Datex, Relaxograph,
      Finland). The infusion rate was adjusted to maintain the height of the first
      twitch (T1) in each train of four at 5-10% of control twitch height. The mean
      duration of infusion was 50.74 +/- 18.06 minutes. The steady state infusion rate
      required to maintain 90% to 95% twitch depression was 83.5 +/- 21.4
      micrograms/kg/min. Five patients developed phase II block (T4/T1 < 0.5)
      designated as IB. The other ten did not develop phase II block as IA. Recovery
      times (T1 = 10.50%, 10-100%) between IA and IB were not statistically
      significantly different. The recovery time of train-of-four fade (T1 = 10% to T1
      = 100% and train of four > 75%) was 5.73 +/- 0.43 minutes. However, recovery
      times between continuous infusion group and single dose group were significantly
      different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302153
TI  - [Pheochromocytoma].
AB  - Pheochromocytoma is a rare tumor which develops in chromaffin cells and secrets
      excessive catecholamine. Unless patients harboring this uncommon tumor are
      exactly diagnosed preoperatively, well prepared, and protected from the effects
      of excessive catecholamine release, they are greatly at risk when undergoing any
      surgical procedures. This brief review contains the clinical symptoms, signs and
      syndromes associated with pheochromocytoma, the diagnostic methods which may
      identify and localize the lesion, the regimens of preoperative preparation and
      pharmacological control, the anesthetic management which has proved safe and
      effective in many patients, the anesthetic agents which may be contraindicated in
      some patients, and the postoperative management.

PMID- 8302154
TI  - [Anesthetic management of intraoperatively diagnosed pheochromocytoma--a case
      report].
AB  - Pheochromocytoma is a catecholamine secreting tumor originating from the adrenal
      medulla (up to 90%), or from the chromaffin tissue along the paravertebral
      sympathetic chain. The hallmark of pheochromocytoma is paroxysmal hypertension
      associated with diaphoresis, headache, tremulousness, and palpitations. The triad
      of diaphoresis, tachycardia, and headache in hypertensive patients is highly
      suggestive of pheochromocytoma. Other symptoms like flushing, nausea, vomiting,
      personality changes, and visual disturbances may however cast doubt on the
      diagnosis of pheochromocytoma. Death resulting from pheochromocytoma is usually
      due to congestive heart failure, myocardial infarction, or intracerebral
      hemorrhage. Although less than 0.1 percent of patients with hypertension have a
      pheochromocytoma, nearly 50 percent of the mortality with unsuspected
      pheochromocytoma occurred during anesthesia and surgery or parturition. Patients
      of unsuspected pheochromocytoma have higher risk for surgery, because some
      mandatory pre-op medical treatments might have been ignored. It is also a
      challenge to anesthesiologists to handle unsuspected hypertensive crisis during
      anesthesia and surgery. We presented such a case of unexpected Pheochromocytoma
      which was mis-diagnosed by the surgeon and was treated as an ordinary adrenal
      gland tumor and was scheduled for surgical operation. When the patient was
      undergoing excision of the tumor, manipulations of the tumor initiated an
      tremendous elevation of the blood pressure. Upon reviewing her history of
      normotension with visual disturbance, nausea and restlessness, she was immediate
      treated as with a pheochromocytoma. Appropriate managements were applied to
      control her abnormally high fluctuating blood pressure with success and with no
      complications or adverse effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302155
TI  - [Postoperative hypoglycemia after pheochromocytoma resection].
AB  - A case of severe hypoglycemia (30 mg/dL) after resection of unilateral
      pheochromocytoma is reported. Consciousness regained after 20 gm dextrose water
      was given intravenously. Rebound insulin storm is highly suspected as the main
      mechanism for the development of post-operative hypoglycemia. Administration of
      alpha and beta adrenergic blockers may also contribute to the severity of the
      hypoglycemia. Closely monitoring blood sugar level during the perioperative
      period is the only way to prevent the occurrence of such a catastrophe.

PMID- 8302157
TI  - gamma-Aminobutyric acidA receptor regulation by a chloride-dependent kinase and a
      sodium-dependent phosphatase.
AB  - gamma-Aminobutyric acidA (GABAA) receptors are linked to ion channels which
      mediate many aspects of neural inhibition. Although the effects of
      phosphorylation on GABAA receptor function have been widely studied, the actual
      role of phosphorylation in the regulation of these receptors still remains
      controversial. In recent reports, we have described the effects of
      phosphorylating/dephosphorylating enzymes on the regulation of GABAA receptors in
      a rat cortical slice preparation (Shaw et al., Mol. Neuropharmacol., 2 (1992) 297
      302; Shaw and Lanius, Dev. Brain Res., 70 (1992) 153-161; Pasqualotto et al.,
      Neuroreport, 4 (1993) 447-450) and predicted that ionic co-factors are involved
      in mediating the regulation of GABAA receptors by kinases and phosphatases. In
      the present report, the effects of chloride, sodium, potassium, and calcium were
      examined alone and in the presence of cAMP-dependent protein kinase (protein
      kinase A) or alkaline phosphatase. The results showed a decrease in [3H]SR 95531
      (GABAA receptor antagonist) binding after incubation with chloride alone; this
      decrease was further enhanced in the presence of protein kinase A. Both effects
      could be blocked by a protein kinase A inhibitor. Conversely, an increase in
      [3H]SR 95531 binding was observed after incubation with sodium alone; this
      increase was further enhanced in the presence of alkaline phosphatase. In both
      cases these increases in binding could be blocked by sodium orthovanadate, a
      phosphatase inhibitor. Potassium was ineffective under all conditions; calcium
      showed enzyme-independent effects at low concentrations only. These results
      suggest the existence of a novel chloride-dependent protein kinase which may have
      significant sequence homology to protein kinase A, and a novel sodium-dependent
      phosphatase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302156
TI  - Glial cell-specific expression of the serotonin 2 receptor gene: selective
      reactivation of a repressed promoter.
AB  - The 5' flanking region of the 5-HT2 receptor gene has been cloned, sequenced and
      its transcriptional regulatory functions analyzed. The promoter lacks an
      identifiable TATA motif, and utilizes at least 11 clustered start sites. Promoter
      function was analyzed by transient assays in rat C6 glioma cells, which were
      shown to express the endogenous 5-HT2 receptor gene, as well as in rat CREF and
      human HeLa cells which do not express the endogenous gene. The basal promoter
      functioned equally well in all three cell lines; and a repression domain, located
      upstream of the basal promoter, inhibited activity of the promoter in all three
      cell lines. A far upstream cell specific activator domain restored promoter
      activity in C6 glioma cells, but did not reactivate the silenced promoter in CREF
      or HeLa cells. The upstream activator domain, repressor domain and basal promoter
      functioned in concert to achieve cell type specific expression. The activator
      domain did not direct C6 glioma cell specific expression in the absence of the
      repressor domain or in constructs carrying a heterologous basal promoter. These
      results indicate that glial cell expression of the 5-HT2 receptor gene is
      achieved through a cell type specific reactivation of a repressed promoter.

PMID- 8302158
TI  - Cell type-specific negative regulatory element in low-affinity nerve growth
      factor receptor gene.
AB  - Developmental changes in the expression pattern of the low-affinity nerve growth
      factor receptor (LNGFR) gene suggest a complex mechanism of gene regulation. We
      demonstrate the presence of a negative regulatory element (NRE) localized to a 40
      base pair (bp) segment, -1731 to -1690 bp upstream from the translation start
      site in the LNGFR gene. The NRE possesses two tandemly arranged sequences with
      similarity to immunoglobulin gene enhancer E-boxes. The NRE is active in neurons
      and neuronal cell lines but not in astrocytes. Electrophoretic mobility shift
      analysis (EMSA) demonstrates changing expression pattern of proteins binding to
      the NRE in developing nervous system. Since the specific binding of the proteins
      to the NRE is competed with oligonucleotides containing E-box sequences we
      suggest that factor(s) responsible for down regulation of LNGFR gene include
      members of the helix-loop-helix class of transcription factors.

PMID- 8302159
TI  - Human tau isoforms confer distinct morphological and functional properties to
      stably transfected fibroblasts.
AB  - Tau protein is a neuronal microtubule-associated protein that promotes the
      assembly and stability of microtubules. To evaluate the biological significance
      of tau isoform diversity, NIH-3T3 cells were stably transfected with cDNAs
      encoding each of the six isoforms present in human brain. Cells expressing
      different isoforms developed distinct morphologies. Cell lines expressing 3
      repeat tau isoforms developed large flat cell bodies while cells expressing 4
      repeat isoforms had small, round cell bodies. All transfected cell lines, except
      those expressing the shortest tau isoform, displayed very long thin neurite-like
      processes. Tau colocalized with microtubules in both the cell body and the long
      processes in all of the tau-transfected cells. Tau also displayed a diffuse
      amorphous staining pattern that was concentrated around the cell nucleus.
      Microtubule bundling was not enhanced in any of the transfected cells as compared
      to untransfected controls. The transfected cells showed increased resistance to
      colchicine treatment. Thus, different tau isoforms can confer unique cellular
      morphologies to 3T3 cells and can alter the susceptibility of these cells to a
      microtubule depolymerizing agent.

PMID- 8302160
TI  - Phosphorylation of tau protein in tau-transfected 3T3 cells.
AB  - The tau protein of Alzheimer paired helical filaments (PHFs) is aberrantly
      phosphorylated, as evidenced by its reactivity with several phosphate-dependent
      antibodies. We sought to identify whether this unusual phosphorylation state
      exists in tau expressed by transfected NIH 3T3 fibroblasts. Immunoblot analysis
      of cell clones transfected with constructs for either the 3-repeat or 4-repeat
      isoforms of tau revealed two tau bands, with the lower band migrating with
      unmodified tau in each case. Antibodies T3P and tau-1 were used to probe these
      bands, as they also react with PHF-tau in a phosphate-dependent manner. The
      epitopes for both antibodies were phosphorylated in both tau isoforms. Only the
      upper band was phosphorylated at the T3P site whereas phosphorylation at the tau
      1 site was not always associated with a shift of tau mobility on gels. Tau in
      both bands was soluble, in contrast to PHF-tau, and was competent to bind to
      exogenously added bovine microtubules. Colchicine treatment of the cells resulted
      in an inhibition of phosphorylation at both sites, through an unknown mechanism.
      In conclusion human tau expressed in 3T3 cells was phosphorylated at the T3P and
      tau-1 sites as is PHF-tau, although no PHFs formed and the phosphorylated tau was
      competent to bind to microtubules.

PMID- 8302161
TI  - Quantitative measurement of calretinin and beta-actin mRNA [correction of mRNAIN]
      in rat brain micropunches without prior isolation of RNA.
AB  - A microdissection technique for quantitation of neurochemicals in discrete brain
      nuclei has been applied to quantitative measurement of mRNA. The method permits
      quantitation of low abundance mRNA from submilligram amounts of tissue (10-500
      micrograms protein). Discrete nuclei and other regions of the brain are
      solubilized in concentrated guanidine thiocyanate solution, mRNA is directly
      hybridized with riboprobes, and detected with a ribonuclease protection assay.
      This method eliminates the necessity for RNA isolation from solid tissue. No
      assumptions regarding RNA recovery are necessary since tissue specimens are
      solubilized, hybridized and treated with ribonuclease in a single tube. We have
      determined the mRNA levels of calretinin, a predominantly neuron-specific calcium
      binding protein in microdissected nuclei and other regions of rat brain. For
      interassay comparison, measurement of sample protein and beta-actin mRNA permits
      normalization and quantitation in terms of these internal controls. The quantity
      of calretinin mRNA ranged from 281 +/- 35 fg/micrograms protein in the thalamic
      paraventricular nucleus to 2.3 +/- 0.5 fg/micrograms protein for the cerebral
      cortex. The calretinin/beta-actin ratios ranged from 79.9 +/- 9.3% to 1.3 +/-
      0.1%, respectively. The combination of microdissection techniques with a lysate
      RNase protection assay: (1) establishes this technique as quantitative for
      detection of high and low abundance mRNAs from microdissected brain specimens;
      (2) bypasses the inefficiencies and uncertainties associated with isolating RNA;
      and (3) enables large numbers of determinations from discrete brain nuclei to be
      analyzed in 2 to 3 days.

PMID- 8302162
TI  - Glutamic acid decarboxylase gene expression in thalamic reticular neurons
      transplanted as a cell suspension in the adult thalamus.
AB  - The goal of the present study was to determine whether alterations in neuronal
      morphology and connections in thalamic grafts were accompanied by changes in the
      expression of mRNA encoding glutamic acid decarboxylase (GAD), the key enzyme in
      the synthesis of GABA, the normal neurotransmitter of neurons of the thalamic
      reticular nucleus. Cell suspensions of rat fetal tissue containing both thalamic
      reticular nucleus and ventrobasal primordia were transplanted into the
      excitotoxically lesioned somatosensory thalamus of adult rats. Levels of
      messenger RNA (mRNA) encoding GAD (Mr 67,000; GAD67) were measured 7 days to 4
      months following transplantation via quantitative in situ hybridization with 35S
      radiolabeled antisense RNAs. Expression of GAD67 mRNA in the thalamic reticular
      nucleus was analyzed in parallel in rat pups between 0 and 30 days postnatally,
      and in adult animals. As already observed with immunohistochemistry, transplanted
      neurons of the thalamic reticular nucleus did not group in specific clusters but
      rather mingled with unlabeled (putatively ventrobasal) neurons. Levels of
      labelling for GAD67 mRNA per neuron increased over time and reached adult levels
      during the third week post-grafting, i.e. 2 weeks after the theoretical birthdate
      of the neurons (grafted at embryonic days 15-16). Similar values were observed
      and a plateau was reached at similar time points during normal ontogeny. The
      results suggest that, in contrast to morphology and size of the neuronal cell
      bodies, gene expression of GAD67 develops normally despite the ectopic location
      of neurons of the thalamic reticular nucleus in the somatosensory thalamus, the
      abnormal connectivity and the lack of segregation from non-GABAergic
      neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302163
TI  - Developmental and environmental changes in GAP-43 gene expression in cat visual
      cortex.
AB  - Northern/slot blot analysis was used to determine postnatal developmental and
      environmentally induced changes in the level of expression of GAP-43 mRNA in
      visual and frontal cortex. Both structures showed a precipitous decline during
      the first 5 weeks and a slight further decline to adult levels. Dark rearing
      resulted in a significant elevation of GAP-43 mRNA which was eliminated by brief
      visual experience. This effect was specific to visual cortex and did not occur in
      frontal cortex. The effect also did not occur in normal adult cats placed in
      prolonged darkness, indicating that GAP-43 mRNA levels are not simply activity
      dependent and are altered by visual input only during early postnatal life. These
      results are consistent with a role for GAP-43 in the state of visual cortical
      plasticity.

PMID- 8302164
TI  - Vasoactive intestinal polypeptide precursor mRNA exhibits diurnal variation in
      the rat suprachiasmatic nuclei.
AB  - Vasoactive intestinal polypeptide (VIP), which is synthesized in the
      ventrolateral subdivision of the suprachiasmatic nucleus (SCN), the circadian
      pacemaker in the mammalian brain, is suggested to mediate information on
      environmental light. Diurnal rhythms of VIP precursor mRNA in the SCN was
      determined in the present study by Northern blot hybridization with an antisense
      RNA probe in rats kept under light-dark conditions. VIP precursor mRNA was found
      most abundant during the dark phase, as light exposure suppressed VIP precursor
      mRNA. This suppression, however, did not last throughout the light phase and VIP
      precursor mRNA returned to the level before the onset of light after 8 h in
      light, suggesting that VIP mRNA responds to photic cues and not to light per se.
      This is in contrast to the sustained suppression of VIP peptide level in the SCN.
      It indicates that VIP mRNA is acting at a stage of light information processing
      upstream to VIP peptide in the circadian pacemaker.

PMID- 8302165
TI  - Differential immunocytochemical localization of GABAA receptor gamma 1 and gamma
      2 subunits in the rat brain.
AB  - Subunit-specific polyclonal antisera against the GABAA receptor gamma 1 and gamma
      2 subunits were raised in rabbits and used for immunoblotting and
      immunocytochemistry of the rat brain. Each subunit protein was differentially
      distributed even in the region like cerebellar cortex where mRNAs of both
      subunits were distributed in the same manner. This may indicate that GABAA
      receptor gamma 1 and gamma 2 subunit proteins are subject to a subunit-specific
      subcellular sorting mechanism.

PMID- 8302166
TI  - Abnormal distribution of retinal clusterin in retinitis pigmentosa.
AB  - Increased expression of clusterin mRNA is associated with neurodegenerative
      states, including retinas affected by retinitis pigmentosa (RP). We have
      investigated the distribution of immunoreactive clusterin in normal and RP
      affected retinas. Reactivity at the inner limiting membrane, plexiform layers,
      and photoreceptors in normal retina accords well with clusterin's postulated role
      as a membrane protective agent. In RP-affected retina the organized distribution
      is lost and overall reactivity appears decreased. The changes in this case may
      reflect increased turnover or removal of clusterin, perhaps via interaction with
      components of the immune system.

PMID- 8302167
TI  - Comparison of clusterin gene expression in normal and dystrophic human retinas.
AB  - To gain insight into the mechanisms underlying altered clusterin expression in
      retinal degeneration, the cellular distribution of clusterin mRNA in normal and
      in retinitis pigmentosa-affected retinas was compared using in situ
      hybridization. In contrast to the normal retina, where clusterin mRNA is
      localized in the inner nuclear and ganglion cell layers, a clustered distribution
      is observed throughout the dystrophic retina. The results indicate an expression
      of clusterin gene in normal retinal neurons and suggest that its altered
      regulation in neurodegeneration is not purely a glial cell phenomenon.

PMID- 8302168
TI  - [Piezoelectric vibration blood coagulography as a method for assessing the
      functional state of the hemostatic system].

PMID- 8302169
TI  - [A solid-state reference sample of iodine radionuclide activity for checking
      radiometers and a method for its production].
AB  - This development relates to nuclear engineering, concerns the sources of ionizing
      radiation of iodine radionuclides and the ways of their manufacture. The iodine
      radionuclides are used for calibration of radiometers that measure the specific
      activity of iodine radionuclide in biological specimens, in particular for their
      use to identify noncancer diseases. The purpose of the paper is to design a
      routine activity sample for iodine radionuclide in the solid-state source for
      transfer of an iodine radionuclide activity unit from the reference iodine
      radionuclide activity unit to an operating meter with a simultaneous decrease in
      testing errors and an increase, in terms of iodine radionuclide half-life, in the
      life of the reference sample by stabilizing the activity unit of iodine
      radionuclide (in terms of its half-life) by eliminating the process of
      sublimation of iodine radionuclide from the working surface of the source. The
      objective is achieved by the fact that the radionuclide is replaced on the lower
      internal build-up part of the container, fixed with the upper internal build-up
      part, then kept for at least 10-12 hours at least at 18-20 degrees C, packed into
      a hollow container and sealed with epoxide resin. According to the proposed
      technical design, reference activity samples of iodine radionuclide in the solid
      state radiometric source with a preset activity value have been prepared. The
      testing error for iodine radionuclide activity is minimal and equal to 1.0-3.0%
      at a 0.95 confidence.

PMID- 8302170
TI  - [The prospects for creating phototherapy sources of luminescent monochromatic
      radiation].
AB  - The author shows that new prospects in the design of phototherapeutic light
      sources are opened up by the active fibers containing luminescent contaminations.
      The sources of luminescence monochromatized incoherent radiation, lumbar, can
      provide a possibility of selecting a light band, a continuous or impulse
      radiation and other advantages.

PMID- 8302171
TI  - [The choice of the dimensions of the blanks for medical instruments in order to
      obtain the optimal layout of the sheet material].
AB  - The proposed system of the location and spacing of blanks will optimize the
      cutting of sheet material in an automatic mode by using the parametric
      rearrangement of a drawing of a medical instrument blank. The routine drawing
      "Autocad" in the DXF format is used as a parametric drawing in the system. The
      system has no limitations on the complexity of a rearranged drawing and in all it
      will provide one- and two-row location and spacing of the blanks, as well as
      location and spacing of blanks with rotation and revolution of a band and give a
      table of values required for designing the working parts of blanking dies.

PMID- 8302172
TI  - [A system for the automatic design and control of dental drills and for the
      preparation of control programs for their fabrication on tool grinders].
AB  - The paper deals with the automatic designing control system for dental drills,
      the procedure of designing in the system. It also contains data on the minimum
      pattern of hardware components.

PMID- 8302173
TI  - [A system for modelling the process of the molding of ring-shaped medical
      instruments during grinding and the automated preparation of the control programs
      for machine tools with numerical-program control].

PMID- 8302174
TI  - [A generalized model of a biotechnical system].
AB  - The author proposed a generalized model which determines the structural
      properties of the system (relationships between its elements) invariantly to the
      type of these elements and to their functional application. To reflect the
      interactions in the system to distribute, transport, generate, and accumulate the
      functional environments, the author has used only four elementary monoprocessors
      (a distributor, a generator, a transmitter, and an accumulator) which are united
      into diprocessors (communication channels, transmitters, and receivers),
      communication systems and polyprocessors. The whole system is presented as
      polyprocessors interconnected with transport channels.

PMID- 8302175
TI  - [The organization of the automated creation and storage of the technical
      documentation for medical instruments in the electronic archive of an
      enterprise].

PMID- 8302176
TI  - [A unit complex for the automated creation, control and archiving of technical
      documentation for medical instruments].

PMID- 8302177
TI  - [Medical instruments and the market].

PMID- 8302178
TI  - [The physicochemical properties and biological characteristics of metals for
      medical instruments].
AB  - The metals having antimicrobial properties are of great interest in reducing
      pyoseptic complications in patients operated on when implants and medical
      instruments which contact with the body long are manufactured. The paper gives
      brief information on the physicochemical, antimicrobial, and toxic properties of
      a number of metals, on the mechanism of their toxic action.

PMID- 8302179
TI  - [Single-channel and multichannel micropipettes with a regulatable dosage volume].

PMID- 8302180
TI  - [Sintered diamond heads for the machining of metal-ceramic dentures].

PMID- 8302181
TI  - [Basic trends in the design of medical instruments].

PMID- 8302182
TI  - [A set of instruments for the diagnosis and treatment of uterine diseases].

PMID- 8302183
TI  - [Medical instruments for laser operations on the parenchymatous organs of the
      abdominal cavity].

PMID- 8302184
TI  - [Hemostatic clamps with improved functional properties].

PMID- 8302185
TI  - [The antimicrobial properties of metals and coatings for medical articles].
AB  - The in vitro experimental studies have shown that samples coated with vacuum
      technology-made materials, such as titanium mixtures with chromium, hafnium,
      zirconium, and copper have antimicrobial properties against staphylococci,
      Escherichia coli, Proteus, Pseudomonas aeruginosa. The impact of the coatings on
      bacterial cells is selective and ambiguous.

PMID- 8302186
TI  - [The aseptic instability of joint implants].

PMID- 8302187
TI  - [Psychiatric emergency: between outer and inner world].
AB  - After a brief premise on social change factors of our contemporary society and on
      their impact on the affections and relationships of individuals, psychiatric
      emergency is considered as it relates to institutional response. "Maternal" and
      "paternal" roles of the hospital as it assists those who request help and some
      defensive modalities for decompensated patients are proposed. The article ends by
      hoping for a greater readiness to listen: this approach would favour the capacity
      of the mind to avoid defensive acting-out.

PMID- 8302188
TI  - [Diagnosis-specific psychotherapy].
AB  - The paper outline the fundamental features of a psychotherapeutic method which
      combined and integrates a psychosocial approach with a biological one. The basic
      concepts which justify an integrated approach are illustrated and the main stages
      of the technique are described. The treatment focuses on the definition of a
      diagnosis in line with the criteria of DSM-III-R; based on the diagnosis the
      therapist tries to identify the possible interactions between the symptomatic
      characteristics of the mental illness and its implications in a psychosocial
      context, before analysing them together with the patient. The method can be
      combined with all major traditional models of psychotherapy and does not rule out
      more in-depth analysis.

PMID- 8302189
TI  - [The father's role and dysorexia].
AB  - Of all eating disorders it is widely acknowledged that dysrexia has increased;
      this syndrome appears most frequently to affect the more affluent socio-economic
      classes. This paper focuses on a single case from which more general conclusions
      are then drawn. After an earlier episode of bulimia, a girl suffering from
      anorexia was found to live in a family context in which the father provided a
      weak psychological reference point. He was often away on work during the girl's
      childhood and only takes part in the family life as the provider of material
      wellbeing without playing a direct affective or pedagogical role. A situation of
      this type represents a way of fulfilling family roles in today's society where
      ensuring the family's comfortable lifestyle acts as a substitute for the
      affective role which the parent is not able to sustain due to unresolved neurotic
      nuclei. Society can now augment certain forms of defence in view of efficiency
      and productivity which detract from a genuine personal evolution. This leads to
      the development of neuroses in the younger generation which the mental health
      services must identify and correct using new psychopedagogic proposals.

PMID- 8302190
TI  - [Clinical and therapeutic aspects of alcohol withdrawal syndrome].
AB  - In this review the authors describe the symptomatology, and the etiopathogenetic
      hypothesis of alcohol withdrawal syndrome. Many drugs are used in the treatment
      of alcohol withdrawal syndrome: carbamazepine, clonidine, chlormethiazole,
      phenytoin and other compounds; actually benzodiazepines are the most important
      drugs for symptomatic relief to prevent major withdrawal syndrome. Particularly
      attention is recommended to the period of suspension with the aim of reducing
      alcohol consumption and correcting alcohol-related psychosocial problems.

PMID- 8302191
TI  - [Clinical consistency in the diagnostic approach to the patient. Notes relating
      to the use of psychometric procedures in clinical psychiatry].
AB  - The authors underline the difficulties of the introduction and use of the
      psychometric approach in psychiatry. The use of protocols for the standardised
      evaluation and measurement of psychopathological phenomena is soon revealed to be
      open to criticism regarding the objective character of the object of the inquiry
      in psychiatry; at the same time there is an equally legitimate need not only for
      "forms" but also clinical "contents" without which the doctor's role loses its
      traditional target.

PMID- 8302192
TI  - [Foreseeable and possible developments of Law 180 and its impact on various forms
      of psychotherapy. Brief notes on the relationship between psychoanalysis and
      politics].
AB  - The author points out that the law of reform of mental health has had a strong
      influence above all upon the pharmacological field. Finally he makes a few
      remarks about the connections between the practice of psychiatry and political
      ideologies.

PMID- 8302193
TI  - [Treatment of insomnia related to depressive disorders. Effects of zolpidem
      versus flunitrazepam administration and withdrawal evaluated in a double-blind
      study].
AB  - The effects of a 15 day treatment with zolpidem (10 mg) and with flunitrazepam (1
      mg) on Insomnia Disorders Related to Depressive Disorders (DSM-III-R) have been
      evaluated on 30 depressive in-patients (mean age 42.3 +/- 9.8). The trial has
      been carried out on double blind condition after 5 days of single blind placebo
      administration. Withdrawal effects have been evaluated in single blind condition
      on a 10 day period after drugs discontinuation. Patient's diagnosis was Major
      Depression or Dysthymia according to DSM-III-R; inclusion criteria were insomnia
      (total sleep time < or = 6 h, sleep latency > or = 30 min, wake after sleep onset
      > or = 30 min, No of awakenings > or = 3) refractory to clomipramine
      administration at constant dose (75-150 mg/day among patients). Both drugs have
      been followed by a rapid, significant diminution of insomnia as demonstrated by
      significant changes at Stanford Sleepiness Scale and Saint Mary Hospital Sleep
      Questionnaire and by a significant reduction of HDRS total scores. No clinical
      phenomena of rebound insomnia were detected after zolpidem and flunitrazepam
      withdrawal. Drug discontinuation however was followed by the slow increase of the
      score on insomnia items, approximating basal values at the end of the 10 day
      period after zolpidem and flunitrazepam withdrawal. A parallel increase of HDRS
      total score was also detected; HDRS changes were mainly due to the increase of
      the items anxiety somatic, general somatic symptoms, gastrointestinal somatic
      symptoms, hypochondriasis. The study confirms the therapeutic efficacy of
      zolpidem and of flunitrazepam in the treatment of insomnia resistant to
      antidepressant drugs in depressed patients. They also suggest that early drug
      discontinuation is frequently associated with clinical relapse of insomnia and of
      several other symptoms correlated with the affective pathology.

PMID- 8302194
TI  - [Atypical depression and cognitive psychotherapy: treatment in a mental hospital
      for prisoners. Case report].
AB  - The authors report the case of a patient suffering for atypical depression.
      During hospitalization in criminal mental hospital, the presuppositions to
      reinstate the patient in his original environment are created by the use of
      cognitive and ludo-ergo-therapy.

PMID- 8302195
TI  - Carbohydrate enriched diets and bacterial glycosidases in rat faeces.
AB  - The expression of some faecal hydrolytic enzymes in rats fed for 4 months on
      sucrose or starch enriched diets was compared with a standard diet. The assay
      reliability was confirmed for animal and experimental variability. The beta-D
      glucuronidase and beta-D-glucosidase activities were always higher in rats fed on
      starch than on other diets. N-acetyl-beta-D-glucosaminidase and N-acetyl-beta-D
      galactosaminidase showed decreased activity when passing from a standard to a
      sucrose, and from a sucrose to a starch diet. There was little modification in
      the levels of faecal alpha-D-glucosidase, sulphatase and protease with the
      various experimental diets.

PMID- 8302196
TI  - Differentiation of thermophilic species of Campylobacter, in particular C. coli
      and C. jejuni, with atypical characteristics, by analysis of protein-banding
      profiles on non-denaturing polyacrylamide gels.
AB  - The protein-banding patterns after electrophoresis of 23 strains of thermophilic
      Campylobacter, including 17 strains of C. coli and C. jejuni which had atypical
      characteristics with respect to the hydrolysis of hippurate and susceptibility to
      nalidixic acid, were characterized. Of the atypical strains of C. coli and C.
      jejuni 16 out of 17 gave protein-banding patterns which were essentially
      identical to those of typical strains, and distinct patterns were obtained from
      strains of two other species. The banding patterns of soluble proteins on non
      denaturing polyacrylamide gels after electrophoresis appear to be useful for the
      differentiation of atypical strains of C. coli and C. jejuni. Strain 11791 which
      was originally identified as C. coli was identified as C. lari from its protein
      banding profile.

PMID- 8302197
TI  - Characterization of a plasmid codifying the synthesis of a beta-lactamase
      produced by Shigella flexneri.
AB  - The resistance to beta-lactam antibiotics shown by a strain of Shigella flexneri
      was plasmid-coded. This plasmid, pMAM-1, when transferred to Escherichia coli K
      12 by conjugation, presented the same molecular weight (100 kbp) and conferred
      the same high level of resistance to ampicillin in the transconjugant as in the
      wild type strains (MIC, 2048-4096). Restriction analysis of the plasmid in
      transconjugants revealed various restrictive sites to some endonucleases (i.e.
      Bam HI, Eco RI, Pst I, Nco I, Cla I, Sf I and Sau 3AI, Nhe and Hin dIII), and no
      restrictive sites at all for other endonucleases (such as Xho I, Dra I, Kpn I,
      and Sal I). Some restricted DNA fragments were appropriate for cloning and
      isolation of the beta-lactamase gene present in Shigella flexneri UCSF 129. This
      work provides the first step in this direction.

PMID- 8302198
TI  - Effect of five irreversible inhibitors on beta-lactamase from Shigella flexneri
      UCSF-129.
AB  - The effect of five irreversible inhibitors on purified enzyme from Shigella
      flexneri USCF-129 and also in vitro, was investigated. The I50 was 0.091, 0.30,
      0.40 and 0.87 microgram/ml for 6 beta-iodopenicillanic, clavulanic, olivanic and
      6 beta-bromopenicillanic acids, respectively, and 255 micrograms/ml for
      sulbactam. The synergic responses of these inhibitors (10 micrograms/ml) were
      studied with ampicillin and cephradin on S. flexneri. The MIC of ampicillin was
      reduced by 128 times using 6 beta-iodopenicillanic, 6 beta-bromopenicillanic and
      clavulanic acids. This indicates that the beta-lactamase of S. flexneri is a
      penicillinase. Since these inhibitors have a strong action against the beta
      lactamase and last for at least 6 h, further work is expected to reveal their
      medical value.

PMID- 8302199
TI  - Supplementation of male inhibitory material to lipid A activated human
      mononuclear cell supernatants contributes to the suppression of polymorphonuclear
      cell phagocytosis.
AB  - Human normal peripheral blood mononuclear cells were stimulated with lipid A
      (LA), the biologically active moiety of bacterial lipopolysaccharides. LA
      activated supernatants were able to suppress polymorphonuclear cell (PMN)
      phagocytosis of Candida albicans. This inhibitory activity was enhanced by the
      supplementation of male inhibitory material (MIM) to active supernatants. The
      addition of a recombinant human anti-interleukin-1 beta monoclonal antibody to
      activated supernatants in the absence or presence of MIM diminished or abrogated,
      respectively, the suppressive effect on PMN function. The mechanisms and the
      significance of MIM-mediated inhibition of phagocytosis under these circumstances
      are discussed.

PMID- 8302200
TI  - The role of O-antigen in susceptibility of Serratia marcescens to non-immune
      serum.
AB  - Selection of phage-resistant strains to three different phages, kappa, FSB3 and
      FSB55, whose primary receptor was lipopolysaccharide, enabled several spontaneous
      O-defective mutants to be isolated and characterized. Strains ATCC 274 (0:14),
      2170 (0:14) and NIMA (0:6) showed serum resistance, whereas their O-side chain
      defective mutants exhibited high serum susceptibility. Both alternate and
      classical activation pathways were involved in serum killing activity in Serratia
      marcescens.

PMID- 8302201
TI  - Detection of antiviral and antitumoral fractions of Chenopodium amaranticolor
      leaf extract.
AB  - Based on the fact that Chenopodium amaranticolor extracts showed inhibitory
      activity against tobacco mosaic virus (TMV) and Ehrlich tumour (EA), tests were
      carried out to investigate whether the antiviral and antitumoral activity were
      caused by the same compounds. When the extract was purified by CM Sephadex C-25
      column, after precipitation with 90% ammonium sulphate, twenty active fractions
      against TMV and two pools of fractions active against EA were obtained. Only one
      fraction with high absorbance values at 260 and 280 nm was able to inhibit both
      TMV and EA. When the extract was purified by Bio Gel P-60 column two active
      fractions against TMV and EA were obtained, suggesting that they were contained
      in the 0.01 M fraction of the CM Sephadex column. It is suggested that C.
      amaranticolor leaf extract contained at least two protein-like substances
      manifesting antiviral and antitumoral activity.

PMID- 8302202
TI  - Observations on listerias at dysgenesic concentrations of NaCl.
AB  - Interesting morphological and Gram-stain changes of listerias in relationship to
      the concentration of NaCl were observed. When incubated at 23 degrees C at a
      concentration of 6% (w/v) the listerias tended to form chains, and in
      concentrations of 10-11% NaCl they presented aberrant forms as long filaments,
      some of them forming circles, and they lose affinity for Gram stain. Similar
      changes were observed, but at different concentrations of NaCl, when incubation
      was at 37 degrees C.

PMID- 8302203
TI  - Use of beta-lactam/beta-lactamase-inhibitor combinations as antimycobacterial
      agents.
AB  - Mycobacterium tuberculosis and Mycobacterium leprae develop resistance against
      the drugs used to treat tuberculosis and leprosy, respectively. Now multidrug
      resistant tuberculosis is spreading in many countries, especially with the
      emergence of AIDS. Multidrug treatment is being promoted at present to eradicate
      leprosy. Since M. leprae may also become multidrug-resistant, new approaches have
      to be adopted for controlling mycobacterial diseases. Mycobacteria usually
      synthesize beta-lactamase and are insensitive to beta-lactam antibiotics. M.
      tuberculosis contains a constitutive beta-lactamase; de-repression of beta
      lactamase has been reported in M. leprae. Three different beta-lactam/beta
      lactamase-inhibitor combinations (ampicillin/sulbactam, amoxicillin/clavulanate
      and piperacillin/tazobactam) were used to suppress the growth of several strains
      of mycobacteria (including M. tuberculosis H37Rv) in vitro. Ampicillin/sulbactam
      is a potent bactericidal agent against M. leprae multiplying in mouse foot pads.
      In the present work, ampicillin/sulbactam showed higher activity than the other
      drug combinations. The beta-lactam/beta-lactamase inhibitors are likely to be
      effective as rational therapeutic agents against mycobacterial infections.

PMID- 8302204
TI  - Microwave sterilization of enterobacteria.
AB  - A new method is described which makes it possible to treat metal materials with
      microwaves. In consequence scalpel blades as well as cover glasses contaminated
      with four species of bacteria (Salmonella typhi, Proteus mirabilis, Escherichia
      coli and Pseudomonas aeruginosa) were sterilized. With this method sterilization
      can be achieved quite rapidly (1.5-2 min). Scanning electron microscopy revealed
      a progressive alteration in the morphology of micro-organisms and this proved
      proportional to the microwave exposure time. Only in Proteus mirabilis were no
      modifications found, even after long periods of microwave exposure.

PMID- 8302205
TI  - Rural hospital RNs implement practice-relevant research.

PMID- 8302206
TI  - [Metal resistance of gram-negative bacteria isolated from soil and waste waters
      of industrial regions].
AB  - Metals resistance of 112 strains of gram-negative bacteria isolated from soil and
      wastes around Nizniy Novgorod plants were investigated. MIC of metals varied in
      range between 1-10 mM Ni2+, Co2+, 1-6 mM Zn2+, 1-4 mM Cd2+, CrO4(2-), and 0.1-0.3
      mM TeO3(2-). Bacteria with phenotypes NiCo and NiZnTe are revealed most frequent
      (25.6 and 6.4% accordingly). Plasmid DNAs with size between 2-70 kbp were found
      in 50% isolated strains. It was shown that resistance to cobalt of unidentified
      gram-negative bacterium is determined by plasmid genes. Recombinant plasmid
      contained fragment DNA controlling resistance to cadmium and zinc from
      Pseudomonas spp. strain was constructed by using helper plasmid pULB113.

PMID- 8302207
TI  - [Oxidative dehalogenation of 2-chloro- and 2,4-dichlorobenzoates by Pseudomonas
      aeruginosa].
AB  - The strain Pseudomonas aeruginosa 142 isolated from the utilising PSBs bacterial
      association was capable of growth on 2-chloro- and 2,4-dichlorobenzoates as sole
      carbon sources, but it did not utilize 3-Cl, 4-Cl, 3,5-diCl- and 2,6
      dichlorobenzoates. P. aeruginosa 142 dehalogenated 2-Cl-, 2,4-diCl- and 2,5
      dichlorobenzoates in aerobic conditions. The release of chloride was not observed
      in microaerophilic and anaerobic conditions. The activities of catechol-1,2
      dioxygenase and 4-chlorocatechol-1,2-dioxygenase were found in cell extracts
      after growth of this strain on 2,4-dichlorobenzoate. The presented results
      suggested that oxidative release of chloride in ortho-position is the first step
      of metabolism of 2-Cl-, 2,4-diCl- and 2,5-dichlorobenzoates. The further
      splitting of corresponding catechols is carried out by ortho-pathway.

PMID- 8302208
TI  - Systemic antifungal drugs.

PMID- 8302209
TI  - Mammography instrumentation: recent developments.
AB  - Mammography instrumentation has evolved dramatically in recent years. New, more
      consistent and reliable X-ray generators have been introduced. X-ray tubes with
      sharper imaging capabilities, higher X-ray outputs, and photon spectra tailored
      for breasts of different compositions and thicknesses are available. High
      resolution image receptors which require lower patient dose are in routine use.
      Scatter reduction mechanisms allow images with higher contrast to be produced.
      The consistency of mammographic diagnosis has been improved by the introduction
      of stringent quality control programs which utilize simple phantoms for image
      evaluation and require that the patient dose be kept low. New developments in
      breast diagnosis include the use of digital image receptors and stereotactic
      needle positioning systems. In addition, computer aided diagnostic techniques are
      being developed. With currently available technology, high resolution, high
      contrast, and low dose images can be routinely acquired to aid in the early
      diagnosis of breast disease.

PMID- 8302210
TI  - Direct digital mammography using a scanned-slot CCD imaging system.
AB  - In this paper, the rationale for digital mammography is presented in terms of the
      limitations of conventional mammography. Various approaches to digital image
      acquisition are discussed and the design of a scanned-slot digital mammography
      system currently under development is described. Preliminary results including an
      image of an anthropomorphic breast phantom are presented.

PMID- 8302211
TI  - Anthropomorphic radiological phantoms for mammography.
AB  - Anthropomorphic radiological phantoms are useful in evaluating image quality in
      mammography by providing realistic detection tasks to the observer. Methods for
      creating such phantoms, based on original patient mammograms, are described.
      Photochemical enhancement techniques and application of fractal interpolation
      methods for improving the fine detail information contained in such phantoms are
      discussed. Approaches to incorporating additional calibrated test targets within
      the phantom are also described.

PMID- 8302212
TI  - Technological improvements in mammography over the past 20 years.
AB  - During the past twenty years many significant technological improvements in
      mammographic X-ray equipment and screen-film-processing systems have occurred.
      Today it is possible to obtain mammograms with higher image quality at a
      significantly lower radiation dose compared to mammograms dating back about 20
      years. In this review article, X-ray spectra, limiting geometric resolution,
      characteristic (H & D) curves, modulation transfer function (MTF) and noise power
      spectra (NPS) are used to demonstrate technological improvements in mammographic
      screen-film image quality.

PMID- 8302213
TI  - On-line image verification in radiation therapy: an early USA experience.
AB  - The intense effort in the past 5 to 10 years to develop on-line image
      verification (OLIV) systems is made partly in anticipation of the increased
      verification demands of complex 3-dimensional (3D) conformal radiation therapy,
      and partly to improve on the current practice of weekly treatment verification.
      These systems allow convenient acquisition of daily portal images or many images
      during one treatment session. Systems based on fluoroscopic and scanning
      approaches can now be purchased from various vendors and are being evaluated at
      several radiation therapy centers. The performances of these systems vary, but
      all appear to be adequate for clinical use. At the Mallinckrodt Institute of
      Radiology, we have been conducting clinical on-line imaging for the past 3 years
      using a fiber-optic fluoroscopic system. Daily operation of the system requires
      coordinated participation of the physics and radiation therapy technology staff.
      The major consideration is in the management and evaluation of the large amount
      of verification images about each individual patient. At present, it is not clear
      whether the technology would be cost-effective in the clinical setting. However,
      it is clear that OLIV provides a powerful tool in enhancing our knowledge of
      treatment variation. The information will be invaluable in the development of
      improved treatment techniques. It is also likely that these systems will play a
      important part in the verification of 3D conformal radiation therapy.

PMID- 8302214
TI  - Analysis of stability of human upright posture based upon the measurement of the
      head sway.
AB  - The paper is dealing with the description of a simple and inexpensive technique
      for recording and measuring of the head sway during upright stance. In particular
      the recording system and the evaluation of the body sway data are highlighted.
      The objectives of the head sway signal analysis are the determination of sway
      components in the side-to-side (lateral) direction and forward-backward
      (anteroposterior) direction. It is anticipated that it will be possible to
      extract from the digitized data some information about the transfer
      characteristic and stability margin of the neuromuscular control system concerned
      with the maintenance of equilibrium. Additional information of potential clinical
      significance could be obtained by correlating the measured sway data with
      electromyographically determined changes in the activity of the main postural
      muscles. The information obtained is comparable to that gathered by more
      sophisticated, and more expensive conventional devices. A special feature is the
      easy portability of the system which permits collection of stabilometric data
      even in remote locations, while the analysis on which the diagnostic assessment
      is based can be performed at a later date in a central facility equipped with the
      necessary instrumentation.

PMID- 8302215
TI  - Scanning slit mammography.
AB  - The importance of scatter in mammography and the performance of conventional
      mammographic grids are reviewed. Without scatter control image contrast is
      significantly degraded. Conventional mammography grids improve the situation;
      however, their performance is limited. As a result for 5 to 8 cm thick breasts, a
      more ideal method of scatter control could result in a 25 to 45% improvement in
      contrast over that possible with conventional grids. One such approach is
      scanning slit mammography. The principles of this approach are presented along
      with the design and geometrical specifications of a prototype multiple scanning
      slit unit. The unit has a measured primary transmission of 91% and scatter
      transmission of 3%. Similarly measured performance values for a commonly used
      grid are 62% and 19%, respectively. Compared are images of a 6 cm breast phantom
      obtained with the scanning slit unit and a conventional grid. The scanning slit
      unit achieved noticeably greater image contrast with 30% less radiation. Also
      discussed are the limitations and engineering challenges of the technology.

PMID- 8302218
TI  - Kingdom protozoa and its 18 phyla.
AB  - The demarcation of protist kingdoms is reviewed, a complete revised
      classification down to the level of subclass is provided for the kingdoms
      Protozoa, Archezoa, and Chromista, and the phylogenetic basis of the revised
      classification is outlined. Removal of Archezoa because of their ancestral
      absence of mitochondria, peroxisomes, and Golgi dictyosomes makes the kingdom
      Protozoa much more homogeneous: they all either have mitochondria and peroxisomes
      or have secondarily lost them. Predominantly phagotrophic, Protozoa are
      distinguished from the mainly photosynthetic kingdom Chromista
      (Chlorarachniophyta, Cryptista, Heterokonta, and Haptophyta) by the absence of
      epiciliary retronemes (rigid thrust-reversing tubular ciliary hairs) and by the
      lack of two additional membranes outside their chloroplast envelopes. The kingdom
      Protozoa has two subkingdoms: Adictyozoa, without Golgi dictyosomes, containing
      only the phylum Percolozoa (flagellates and amoeboflagellates); and Dictyozoa,
      made up of 17 phyla with Golgi dictyosomes. Dictyozoa are divided into two
      branches: (i) Parabasalia, a single phylum with hydrogenosomes and 70S ribosomes
      but no mitochondria, Golgi dictyosomes associated with striated roots, and a
      kinetid of four or five cilia; and (ii) Bikonta (16 unicellular or plasmodial
      phyla with mitochondria and bikinetids and in which Golgi dictyosomes are not
      associated with striated ciliary roots), which are divided into two
      infrakingdoms: Euglenozoa (flagellates with discoid mitochondrial cristae and
      trans-splicing of miniexons for all nuclear genes) and Neozoa (15 phyla of more
      advanced protozoa with tubular or flat [usually nondiscoid] mitochondrial cristae
      and cis-spliced spliceosomal introns). Neozoa are divided into seven
      parvkingdoms: (i) Ciliomyxa (three predominantly ciliated phyla with tubular
      mitochondrial cristae but no cortical alveoli, i.e., Opalozoa [flagellates with
      tubular cristae], Mycetozoa [slime molds], and Choanozoa [choanoflagellates, with
      flattened cristae]); (ii) Alveolata (three phyla with cortical alveoli and
      tubular mitochondrial cristae, i.e., Dinozoa [Dinoflagellata and Protalveolata],
      Apicomplexa, and Ciliophora); (iii) Neosarcodina (phyla Rhizopoda [lobose and
      filose amoebae] and Reticulosa [foraminifera; reticulopodial amoebae], usually
      with tubular cristae); (iv) Actinopoda (two phyla with axopodia: Heliozoa and
      Radiozoa [Radiolaria, Acantharia]); (v) Entamoebia (a single phylum of amoebae
      with no mitochondria, peroxisomes, hydrogenosomes, or cilia and with transient
      intranuclear centrosomes); (vi) Myxozoa (three endoparasitic phyla with
      multicellular spores, mitochondria, and no cilia: Myxosporidia, Haplosporidia,
      and Paramyxia); and (vii) Mesozoa (multicells with tubular mitochondrial cristae,
      included in Protozoa because, unlike animals, they lack collagenous connective
      tissue).

PMID- 8302220
TI  - [New horizons in pediatric cardiology].

PMID- 8302217
TI  - Bacterial extracellular zinc-containing metalloproteases.
AB  - Extracellular zinc-containing metalloproteases are widely distributed in the
      bacterial world. The most extensively studied are those which are associated with
      pathogenic bacteria or bacteria which have industrial significance. They are
      found practically wherever they are sought in both gram-negative and gram
      positive microorganisms, be they aerobic or anaerobic. This ubiquity in itself
      implies that these enzymes serve important functions for the organisms which
      produce them. Because of the importance of zinc to enzymatic activity, it is not
      surprising that there is a pervasive amino acid sequence homology in the primary
      structure of this family of enzymes regardless of their source. The evidence
      suggests that both convergent and divergent evolutionary forces are at work.
      Within the large family of bacterial zinc-containing metalloendopeptidases,
      smaller family units are observed, such as thermolysin-like, elastase-like, and
      Serratia protease-like metalloproteases from various bacterial species. While
      this review was in the process of construction, a new function for zinc
      containing metalloproteases was discovered: the neurotoxins of Clostridium tetani
      and Clostridium botulinum type B have been shown to be zinc metalloproteases with
      specificity for synaptobrevin, an integral membrane protein of small synaptic
      vesicles which is involved in neurotransmission. Additional understanding of the
      mode of action of proteases which contribute to pathogenicity could lead to the
      development of inhibitors, such as chelators, surrogate substrates, or
      antibodies, which could prevent or interrupt the disease process. Further studies
      of this broad family of metalloproteases will provide important additional
      insights into the pathogenesis and structure-function relationships of enzymes
      and will lead to the development of products, including "designer proteins,"
      which might be industrially and/or therapeutically useful.

PMID- 8302222
TI  - [Prevalence of lactose malabsorption in Roman school children. A H2 breath test
      study using a cow's milk].
AB  - The aim of this study was to evaluate the prevalence of lactose malabsorption in
      a population of 75 (43 males, 32 females) apparently healthy school-children
      using the H2 breath test with cow's milk. The children, ranging in age from 8
      years and 6 months to 15 years and 2 months (mean: 11 years, 7 months) were
      divided into 2 age groups: Group I (no. = 26): age < 11 years and Group II (no. =
      49): age > 11 years. After on overnight fasting, lasting at least 8 hours,
      samples of expired air were collected at 0 time and at 30-min intervals following
      the administration of 250 ml cow's milk for a total time of 3 hours. The H2
      breath concentration was then measured by gas chromatography (Micro-Lyzer
      Quintron Instruments Company mod. 12). A net rise of more than 20 ppm H2 was
      considered as lactose malabsorption. Subjects with symptoms such as excessive
      flatulence, abdominal pain, or diarrhoea, were considered as lactose intolerant.
      Two-hundred and 50 ml of cow's milk (12 g of lactose) was considered a more
      physiological vehicle than the traditional lactose aqueous solution. The examined
      children, all on free diet, showed a fasting alveolar from 0 to 43 ppm (mean +/-
      SD = 7.9 +/- 7.6). Sixty-six children out of 70 (93.3%), who completed the test
      had a total absorption of lactose. Two out of 4 children with lactose
      malabsorption originated from areas (East Africa and Central America), where a
      high incidence of this metabolic disorder is a characteristic findings.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8302221
TI  - [Determinants of body fat in prepubertal age].
AB  - In order to evaluate the factors affecting body fat excess and distribution, we
      have studied children attending the 4th grade of a primary school randomly
      selected in Naples. 52 girls, 58 boys; mean age = 9.6 years (SE +/- 0.1) were
      examined. Among the familial factors assessed, a correlation between parental BMI
      and child's anthropometry was found. Among congenital factors, sex correlates
      with the children's waist/hip ratio ("t" = -2.07; p = 0.05). Moreover the girl's
      percent body fat was higher. These two findings suggest the expression of sexual
      characters in prepubertal age. Systolic blood pressure showed a positive
      correlation with children's percent body fat ("t" = 2.43; p = 0.016) and
      subscapular skinfold thickness ("t" = 1.19; p = 0.05), suggesting an influence of
      these factors on blood pressure level since this age. No correlation was found
      between children's BMI and weight at birth, family history of diabetes,
      hypertension or hyperlipidemia. Among environmental factors, only the mothers
      weight gain during pregnancy ("t" = -2.21; p = 0.03) and breast feeding ("t" = 
      2.07; p = 0.05) correlated with the children's BMI. The correlation between
      children's BMI and waist/hip ratio ("t" = 4.64; p = 0.0001), was not confirmed in
      children who exercise, suggesting a beneficial action of physical activity on
      body fat distribution. The identification in different populations of factors
      associated with childhood obesity is important for prevention planning.

PMID- 8302223
TI  - [Validity of self-assessment of pubertal maturation in early adolescents].
AB  - Self-assessment measures of sexual maturation continue to be used to classify
      pubertal development even though their reliability remains in question. This
      study examined the accuracy of self-assessment measures by early adolescents in
      one setting, during a day hospital. Standardized figure drawings depicting
      Tanner's sexual maturation stages were shown to early adolescents, and subjects
      were asked to rate their own pubertal development. Physical examination by
      physicians was used to corroborate sexual maturation. Participating in this study
      were 50 males (10-17 age) and 50 females (9-16 age). A small concordance rate
      between physical examination and self-assessment has been reported: 14% in males,
      16% in females. There was a tendency for subjects males (48%) to overestimate
      their sexual development at later stages. A great part of the females (40%)
      answered exactly, with a shift to underestimation (36%) for breast stage and
      (54%) for pubic hair stage. So, in our experience, the small concordance between
      physical examination and self-assessment of pubertal maturation can't be used
      like a not controlled test.

PMID- 8302224
TI  - [Child abuse by intoxication].
AB  - Child abuse by toxic substances is not easy to identify due to both the lack of
      signs of physical violence and the high incidence of accidental poisonings.
      Twelve cases of documented abuse, out of 6175 poisonings in children aged 0-13
      years, were registered during 1975-1990 at Genova, Torino and Trieste Children
      Hospitals. In other 139 children the suspicion of abuse couldn't be confirmed. An
      early suspicion of abuse, is needed to prevent abuse and help the child and his
      family.

PMID- 8302216
TI  - Expression of virus-encoded proteinases: functional and structural similarities
      with cellular enzymes.
AB  - Many viruses express their genome, or part of their genome, initially as a
      polyprotein precursor that undergoes proteolytic processing. Molecular genetic
      analyses of viral gene expression have revealed that many of these processing
      events are mediated by virus-encoded proteinases. Biochemical activity studies
      and structural analyses of these viral enzymes reveal that they have remarkable
      similarities to cellular proteinases. However, the viral proteinases have evolved
      unique features that permit them to function in a cellular environment. In this
      article, the current status of plant and animal virus proteinases is described
      along with their role in the viral replication cycle. The reactions catalyzed by
      viral proteinases are not simple enzyme-substrate interactions; rather, the
      processing steps are highly regulated, are coordinated with other viral
      processes, and frequently involve the participation of other factors.

PMID- 8302225
TI  - [Diencephalic syndrome. Case report and review of literature].
AB  - We report the case of a twenty-three month old, normally eating child, affected
      by organic macies and severe dystrophy. After the negative response of blood and
      laboratory examinations let us exclude a malabsorption syndrome, only the
      performance of neuro-radiologic exams showed evidence of a subthalamic tumor as
      the cause of a "Diencephalic syndrome". Diencephalic syndrome or Russel's
      syndrome is a diencephalic tumor induced disease, which sets in the first three
      years of life. The disease clinical markers are a severe emaciation with appetite
      preservation and absence or very scarce evidence of any telltale neurological
      sign. the tumoral histo-pathology most frequently shows a low grade of malignancy
      astrocytoma, whose eradication is very often difficult because of the particular
      anatomic site. Choice treatment includes an excisional biopsy associated to
      chemotherapy and to radiotherapy.

PMID- 8302226
TI  - [Melkersson-Rosenthal syndrome. A case report].
AB  - The Melkersson-Rosenthal syndrome is a rare disease of unknown pathogenesis.
      Classical signs include recurrent facial palsy, lingua plicata and orofacial
      edema. The diagnosis is often difficult when all features are not present at the
      same time: in the literature complete triads occurred in 25-30% of the patients.
      We report a case of Melkersson-Rosenthal syndrome with classical triad of signs
      in a 13 year old boy. The pathology, clinical features and management of this
      disease are discussed: the possible role of food allergy or additives intolerance
      is also examined.

PMID- 8302227
TI  - [Neonatal listeriosis. A case report].
AB  - The author describes a case of early neonatal listeriosis following by a positive
      outcome. The severity of this infection is underlined as well as the need to
      examine carefully the role of listeria monocytogenes as a cause of similar
      influenza-type syndromes in pregnant women.

PMID- 8302219
TI  - ABC transporters: bacterial exporters.
AB  - The ABC transporters (also called traffic ATPases) make up a large superfamily of
      proteins which share a common function and a common ATP-binding domain. ABC
      transporters are classified into three major groups: bacterial importers (the
      periplasmic permeases), eukaryotic transporters, and bacterial exporters. We
      present a comprehensive review of the bacterial ABC exporter group, which
      currently includes over 40 systems. The bacterial ABC exporter systems are
      functionally subdivided on the basis of the type of substrate that each
      translocates. We describe three main groups: protein exporters, peptide
      exporters, and systems that transport nonprotein substrates. Prototype exporters
      from each group are described in detail to illustrate our current understanding
      of this protein family. The prototype systems include the alpha-hemolysin,
      colicin V, and capsular polysaccharide exporters from Escherichia coli, the
      protease exporter from Erwinia chrysanthemi, and the glucan exporters from
      Agrobacterium tumefaciens and Rhizobium meliloti. Phylogenetic analysis of the
      ATP-binding domains from 29 bacterial ABC exporters indicates that the bacterial
      ABC exporters can be divided into two primary branches. One branch contains the
      transport systems where the ATP-binding domain and the membrane-spanning domain
      are present on the same polypeptide, and the other branch contains the systems
      where these domains are found on separate polypeptides. Differences in substrate
      specificity do not correlate with evolutionary relatedness. A complete survey of
      the known and putative bacterial ABC exporters is included at the end of the
      review.

PMID- 8302228
TI  - [Pediatric oncology: results and future therapeutic perspectives].

PMID- 8302229
TI  - [Condyloma acuminatum in children: etiopathogenesis and a review of the
      literature].
AB  - The authors review the literature on the subject of the questions raised by the
      finding of condyloma acuminatum in children. These questions concern its
      epidemiology, the methods of transmission, the existence or otherwise of sexual
      abuse and predisposing conditions, its relationship with various viral serotypes
      and with the onset of neoplasia in adulthood. The most appropriate modes of
      behaviour in relation to individual cases are also discussed and the authors make
      a few comments regarding prevention.

PMID- 8302230
TI  - [Nosologic evaluation of Noonan syndrome and description of nine cases].
AB  - Noonan syndrome was first described over 20 years ago by Noonan and Ehmke. They
      defined a specific group of nine patients with valvular pulmonary stenosis who,
      in addition, had short stature, mild mental retardation, hypertelorism and
      unusual facies. The incidence of Noonan syndrome has been estimated to be between
      1 in 1000 and 1 in 2500 live births. The primary biochemical defect in Noonan's
      syndrome is unknown. We analyzed 9 patients (5 males and 4 females) in an age
      range of 6 months to 10 years and 3 months with Noonan syndrome. Patients were
      diagnosed as having the syndrome if they had characteristic facies and a normal
      karyotype, plus one of the following signs: cardiac defects, short stature or
      undescended testes. All patients have ocular anomalies (epicanthal folds, ptosis
      of eyelids, hypertelorism, downslanting palpebral fissures and ocular proptosis).
      Congenital heart malformations are present in 8 patients and the more frequent
      cardiopath is pulmonary valve stenosis due to a dysplastic or thickened valve.
      Short stature is present in 6 patients and 3 of them are actually on treatment
      with rhGH. A moderate-mild mental retardation is present in 6 patients. Case n. 9
      had a syringomyelia and tethered cord. These malformations are rarely reported in
      Noonan's syndrome.

PMID- 8302231
TI  - [Importance of antigliadin antibodies determination during the follow-up of
      childhood coeliac disease].
AB  - Since their introduction in clinical practice, antigliadin antibodies (AGA) have
      simplified the diagnostic iter of coeliac disease. In addition they have allowed
      us to recognize an even high number of new cases and also to identify new
      clinical forms. While AGA are widely used in the diagnostic phase, their
      determination during follow-up of the disease has been always limited. With the
      present work we observe the behaviour of AGA during the various phases of coeliac
      disease. The study was carried out on 288 coeliac children divided as follows: 96
      at diagnosis, 136 on gluten-free-diet (75 diet adherent and 61 non adherent) and
      56 on gluten-challenge. 145 healthy children were also studied as a control
      group. In all children AGA (IgA and IgG) were determined, with a micro-ELISA
      method, every two months in the children on gluten-free-diet and monthly in the
      children on gluten-challenge. Data obtained showed AGA behaviour strictly related
      to the diet. In fact while children with good compliance to the diet had AGA
      normalization within the 2nd and 6th month, respectively for IgA and IgG,
      children with poor adherence to diet had constantly positive AGA. Noteworthy was
      the AGA behaviour during challenge. Gluten introduction determined a rapid
      increase of IgA and a slow increase of IgG. Our results confirm the usefulness of
      AGA determination during the follow-up of coeliac children giving us the
      possibility to avoid one or more biopsies included in the ESPGAN protocol.

PMID- 8302232
TI  - [Hypersecretive congenital hydrocephalus due to choroid plexus villous
      hypertrophy associated with controlateral papilloma].
AB  - The authors present a case of a nine month-old baby with hypersecretive
      congenital hydrocephalus. The CSF overproduction was the result of a rare
      abnormality of the choroid plexus, a villous hypertrophy of the right ventricular
      choroid plexus and a left ventricular plexus papilloma. Surgical removal of the
      plexus papilloma and the plexectomy of the hypertrophic ventricular structure did
      not ameliorate the hydrocephalus, which has been controlled after a biventricular
      peritoneal shunt. The physiopathological relationship between hydrocephalus and
      choroid plexus abnormalities are reported. The importance of an early diagnosis
      and treatment is stressed. Both hydrocephalus and choroid plexus pathology may
      represent a cause of psychomotor delay, for the little patient the effects of
      which is investigated in this paper.

PMID- 8302233
TI  - [Pyridoxine administration in acute isoniazid intoxication].

PMID- 8302234
TI  - [Performance and utility of a quick immunological method for the measurement of
      HbAlc in a pediatric diabetes unit].
AB  - This study compares the results of a new immunoassay method (DCA2000, Ames) used
      to measure HbAlc concentration in 9 min using 1-microliter capillary blood sample
      with those obtained with an ion exchange traditional method (HPLC, DIAMAT,
      Biorad) in both a non-diabetic and a diabetic pediatric population. All HbAlc
      values were measured in the two methods on the same whole-blood venous aliquot
      after we had excluded differences in HbAlc values measured by DCA2000 on venous
      and capillary blood samples (8.5 +/- 1.4 vs 8.6 +/- 1.4%). Data analysis shows an
      excellent correspondence between the two assays (r = 0.97; p < 0.0001). HbAlc
      values obtained by DCA2000 method in diabetic patients are related to the mean
      value of the blood glucose levels collected at home in the last two months (r =
      0.74; p < 0.003). The percentile distribution of the HbAlc values is similar both
      in DCA2000 (3-- = 4.4; 50-- = 5.3; 97-- = 6.0%) and in HPLC method (3-- = 4; 50--
      = 5; 97-- = 5.9%). Within-run precision for DCA2000 ranges from 3.7 to 1.9% and
      between-run precision from 4.5 to 0.9%. The new immunoassay method gives accurate
      and reliable HbA1c values and compared with HPLC methodology has at least three
      advantages: it does not require venipuncture, provides HbA1c value within 9 miy
      and allows both physician and patient to verify in virtually' real time the
      degree of blood glucose control.

PMID- 8302235
TI  - Altered adult sexual behavior in the male rat following chronic prenatal hypoxia.
AB  - The last week of gestation is a critical period for the sexual differentiation of
      the brain in the rat. Exposure to prenatal stress during this period has been
      shown to demasculinize and/or feminize adult male sexual behavior. Many of the
      neurochemical and endocrine responses to hypoxia are similar to that observed
      under stressful conditions such as restraint stress. Therefore, we examined the
      postnatal consequences on reproductive and nonreproductive sexually dimorphic
      behaviors in male offspring of dams exposed to chronic hypoxia during the last
      week of gestation. In addition, we examined sensorimotor development in offspring
      of both sexes. Pregnant Sprague-Dawley dams were exposed to continuous hypoxia
      (10.5% O2 from gestational day 15 to 21). Offspring were weaned at 22 days of age
      and group housed. Behavioral tests were conducted with littermate
      representatives. In adulthood, male rats prenatally exposed to hypoxia had
      significantly delayed initiation latencies of masculine sexual behavior and
      decreased number of ejaculations, but did not display a significant increase in
      feminine sex behavior potentials. Developmentally, animals exposed to prenatal
      hypoxia did not differ significantly from controls with respect to day of eye or
      ear opening, or the in times of righting reflex, negative geotaxis or cliff
      avoidance. Wire hanging latencies in hypoxic exposed animals were significantly
      greater than controls around the time of eye opening, but did not differ at
      earlier or later ages. A significant effect of hypoxia was detected on stride
      length at 95 days of age, but other aspects of gait patterns were similar to
      controls. No group differences in gait patterns were observed at 17 or 45 days of
      age. In addition, no significant differences were observed in open field
      activity, circadian locomotor activity, saccharin preference, or Morris water
      maze test. This hypoxia regimen did not influence the occurrence of the prenatal
      or postnatal surge of plasma testosterone. Overall, these results provide some
      evidence that, in males, mild, chronic prenatal hypoxia may result in incomplete
      masculinization of adult reproductive behavior in the absence of overt changes in
      perinatal testosterone surges.

PMID- 8302236
TI  - TCDD alters pituitary-adrenal function. I: Adrenal responsiveness to exogenous
      ACTH.
AB  - Plasma ACTH concentrations in 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)
      treated rats (50 micrograms/kg; single, oral dose) were 2.1-, 2.1-, 2.9-, 1.7-,
      1.5-, 2.0- and 3.0-fold greater than control values, respectively, at days 1, 3,
      5, 7, 10, and 14. At days 1 and 5 plasma corticosterone concentrations were
      increased 5.1- and 8.0-fold, respectively; whereas, at days 10 and 14 they were
      depressed to values of 50% and 39% of controls, respectively. Adrenal glands were
      excised from rats treated with TCDD and corticosterone production was assessed.
      Basal corticosterone concentrations produced by treated adrenals were depressed
      to 81%, 72%, and 71% of control values at days 5, 7, and 14, respectively.
      Corticosterone secretion by ACTH stimulated adrenals was equivalent to controls.
      These findings suggest that TCDD exposure decreases the bioactivity of the ACTH
      secreted by the anterior pituitary.

PMID- 8302237
TI  - TCDD alters pituitary-adrenal function. II: Evidence for decreased bioactivity of
      ACTH.
AB  - The present study assessed the ability of primary cultures of rat anterior
      pituitary cells to secrete bioactive ACTH in the presence of 2, 3, 7, 8
      tetrachlorodibenzo-p-dioxin (TCDD). The bioactivity of the secreted pituitary
      cell ACTH was determined by its ability to stimulate secretion of corticosterone
      from primary cultures of rat adrenal cells. ACTH from basal or CRH stimulated
      pituitary cells treated with TCDD was found to be less capable of stimulating
      corticosterone secretion from primary rat adrenal cell cultures than equimolar
      concentrations of ACTH purchased from a commercial supplier. Corticosterone
      secretion from adrenal cell cultures treated with ACTH from basal or CRH
      stimulated pituitary cell cultures exposed to TCDD was decreased by 60 and 70%,
      respectively. The decreased ability to stimulate corticosterone secretion can be
      overcome when extracts of ACTH from pituitary cell cultures treated with TCDD are
      supplemented with commercial ACTH. These findings indicate that TCDD may alter
      the bioactivity of secreted ACTH from the anterior pituitary gland.

PMID- 8302238
TI  - Prenatal exposure to diazepam causes sex-dependent changes of the sympathetic
      control of rat spleen.
AB  - Prenatal exposure to low doses of benzodiazepines has been found to affect immune
      functions (25,26). Because the immune system is controlled by the autonomic
      nervous system, we investigated the sympathetic activity in the spleen for a
      possible contribution to impaired immune function. Twenty-eight-day-old offspring
      of prenatally diazepam- or vehicle-treated Long-Evans rats (diazepam 1.25
      mg/kg/day SC, gestational day 14-20) were injected IP with sheep red blood cells
      (SRBC) to evoke an immune reaction. Baseline splenic noradrenaline (NA) turnover
      was higher in females than in males. Prenatal diazepam treatment resulted in
      reduced NA turnover in the spleen of SRBC-stimulated female, but not male,
      offspring. beta-Adrenergic binding sites in spleen membrane fractions, studied
      with 3H-dihydroalprenolol, showed no differences, indicating that changes in NA
      turnover were not compensated by changes in receptor expression. Sex-specific
      developmental effects of diazepam have been described earlier, e.g., in selective
      effects on perinatal corticosterone levels in female offspring (26).

PMID- 8302239
TI  - Chronic oxytocin treatment during late gestation and lactation impairs
      development of rat offspring.
AB  - The nonapeptide oxytocin (OT) plays an important role in timing and course of
      parturition, and in milk ejection during lactation. Exogenously enhanced OT
      levels were reported to impair body development of rat offspring at birth and
      during postnatal stages. In the present study, this effect was further
      investigated by giving pregnant rats of postcoital day 17 a SC implant that
      delivers small amounts of OT for 2 months (approximately threefold enhancement of
      OT levels), and by introducing a crossfostering protocol for the offspring. A
      slightly reduced body weight of 5 to 7% was again observed in pups born to OT
      implanted dams. When reared postnatally by OT-treated mothers, pups lost weight
      gain (-7 to -10%). During the weaning period, however, body size caught up with
      that of control animals. When nursed by an untreated mother, this recovery took
      place before that period. Growth of control offspring was also hampered when
      placed with OT-treated mothers, but these pups failed to recover from low body
      weights which lasted up to at least 70 days of age (-7%). Daily urine production
      of the pups born of and reared by the OT-treated mothers was reduced at 1 month
      of age, but this effect was only transient and had disappeared at 70 days of age.
      Notwithstanding, the recovery of body growth, brain sizes, and cerebellar DNA,
      i.e., cell content was reduced in the pups born and reared by OT-treated mothers,
      indicative of a lasting effect on brain development.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8302240
TI  - Behavioural effects of prenatal metallic mercury inhalation exposure in rats.
AB  - The effects of administration by inhalation of metallic mercury vapour (Hg0) to
      pregnant rats, approximately corresponding to doses of 0.2 mg Hg0/kg/day (high
      dose) or 0.07 mg Hg0/kg/day (low dose), on the developmental and behavioural
      repertoire of the offspring were studied. Exposure occurred during days 11-14
      plus 17-20 of gestation. The dose levels were selected so as not to induce
      maternal toxicity. Maturation variables such as surface righting, negative
      geotaxis, pinna unfolding, and tooth eruption revealed no differences between Hg0
      treated offspring and controls. Tests of spontaneous motor activity showed that
      the Hg0-treated offspring were hypoactive at 3 months of age but hyperactive at
      14 months. In spatial learning tasks the prenatally exposed offspring showed
      retarded acquisition in the radial arm maze but no differences in circular swim
      maze. A simple test of learning, habituation to a novel environment (activity
      chambers), indicated a reduced ability to adapt. These data suggest that prenatal
      exposure to Hg0 vapour results in similar behaviour changes in the offspring as
      reported for methylmercury.

PMID- 8302241
TI  - Behavioral effects of exposure to organic solvents in Dutch painters.
AB  - The report describes the results of a cross-sectional study of solvent-exposed
      young and older Dutch painters and two age-matched control groups. Both
      traditional and computerized neurobehavioral tests were applied. The study did
      not detect any major differences between the two groups of painters and their two
      age-matched control groups. It is argued that this absence of differences is
      probably not due to a lack of sensitivity of the tests applied or the size of the
      groups studied. The level of exposure was estimated to be within a range at which
      previous authors have reported solvent-induced CNS effects.

PMID- 8302242
TI  - Mid-frequency hearing loss and reduction of acoustic startle responding in rats
      following trichloroethylene exposure.
AB  - Modification of auditory evoked startle responding using prepulse inhibition was
      used to examine the effects of trichloroethylene (TCE) exposure on auditory
      thresholds. Rats were exposed by inhalation to 0, 1500, or 3000 ppm TCE for 18
      hours per day, 5 days a week for 3 weeks. Auditory thresholds for 5 and 20 kHz
      tones were measured before exposure and at 1, 3, and 6 weeks postexposure. In
      addition, hearing thresholds for 5 and 35 kHz tones were examined at a 5-week
      postexposure time-point. Results indicated that hearing thresholds for 20 kHz but
      not for 5 or 35 kHz prepulses were significantly increased in rats exposed to
      3000 ppm TCE. These findings demonstrate a selective hearing loss in the 20 kHz
      range by short-term, high-level TCE exposure. With respect to effects on startle
      responding per se, the present study also found that compared to controls, TCE
      exposed rats failed to show an increase in baseline startle with repeated
      testing. This difference could not be attributed to differences in body weight
      and was persistent throughout the postexposure period.

PMID- 8302243
TI  - Mid-frequency hearing loss in rats following inhalation exposure to
      trichloroethylene: evidence from reflex modification audiometry.
AB  - The present experiments were undertaken to characterize the hearing loss
      associated with 1,1,2-trichloroethylene (TCE) exposure. Adult male Long-Evans
      (LE) rats were exposed to TCE via inhalation (whole body) for 6 h/day for 5 days.
      The concentration-effect function (0-4000 ppm) was determined 3 weeks post
      exposure. Animals were tested for auditory thresholds to 4, 8, 16, 24, 32, and 40
      kHz tones using reflex modification audiometry. In a separate experiment, the
      time course of effects was determined by monitoring 16-kHz thresholds prior to, 1
      h following each of the 5 exposure days, and 5 days, 1, 2, 4, 8, and 12 weeks
      post-exposure. At 14 weeks, these same animals were tested for thresholds to 0.5,
      1, 2, 4, 8, 16, 24, 32, and 40-kHz tones. Results indicate elevated thresholds
      (hearing loss) for the 4000 ppm group at 8 and 16 kHz of approximately 18 and 30
      dB, respectively. Time-course data demonstrated a rapid onset, a 20-dB loss at 16
      kHz after the fifth exposure day, and a 40-dB loss by 2 weeks that persisted up
      to 14 weeks post-exposure. These data demonstrate an atypical and persistent, mid
      frequency hearing loss in rats following inhalation exposure to TCE.

PMID- 8302244
TI  - Prenatal cocaine exposure increases the behavioral sensitivity of neonatal rat
      pups to ligands active at opiate receptors.
AB  - Offspring of dams given 40 mg/kg cocaine HCl (C40) from gestational day 8-20 (E8
      E20), pair-fed dams injected daily with saline (PF), nutritional control dams
      placed on a 40% cellulose based diet and injected with saline daily (NC), and
      untreated dams (LC) were examined. Offspring were given morphine (0.0, 0.1, or
      0.5 mg/kg SC) on postnatal day 10-11 (P10-11) in Experiment 1, and isolation
      induced ultrasonic vocalizations were measured. Planned comparisons indicated
      that both C40 and NC offspring exhibited a greater sensitivity to the morphine
      related decrease in isolation-induced ultrasounds than LC controls. However, the
      presence of an anesthetized littermate suppressed isolation-induced ultrasounds
      equally across all groups, with all groups of offspring spending equal amounts of
      time in physical contact with the littermate. A tail-flick measure of analgesia
      indicated that PF animals were hyperalgesic relative to the other prenatal
      treatment groups; however, no differences in sensitivity to morphine were seen
      across the prenatal groups. In Experiment 2, animals were given the selective
      delta, [D-Pen2,D-Pen5]-enkephalin (DPDPE), and mu, [D-Ala2-NMe-Phe4Gly ol]
      enkephalin (DAMGO) agonists ICV and ultrasonic vocalizations were recorded.
      Results indicated that both C40 and NC offspring were more sensitive to the low
      dose of DAMGO; however, because of the profound suppression of vocalizations seen
      at both doses of DPDPE, potential differences among the prenatal treatment groups
      in responsiveness to the delta agonist were difficult to detect.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8302245
TI  - Effect of prenatal ultrasound exposure on adult behavior in mice.
AB  - Pregnant Swiss mice were exposed to diagnostic levels of ultrasound (3.5 MHz,
      Maximum acoustic output: ISPTP = 1 W/cm2 and ISATA = 240 mW/cm2, acoustic power =
      65 mW) for 10 min on days 11.5 or 14.5 postcoitus (PC). At 3 and 6 months
      postpartum, offspring were subjected to the following behavioral tests: bright
      and dark arena test for locomotor/exploratory activity and passive avoidance test
      for learning and memory. Anxiolytic activity and latency in learning were noticed
      in the ultrasound-treated animals. The effect was more pronounced in the 14.5
      days PC group than in the 11.5 days PC group. But memory was not affected in the
      ultrasound-exposed animals. There was a nonsignificant decrease in the total
      locomotor activity at 6 months of age in all the exposed animals. Thus, the
      present data demonstrate that exposure to diagnostic ultrasound during late
      organogenesis period or early fetal period in mice may cause changes in postnatal
      behavior as evidence by selected adult offspring behavioral tests. However, any
      conclusive statement in this regard should await results from more detailed
      investigations.

PMID- 8302246
TI  - Distribution of neuronal heterotopiae following prenatal exposure to
      methylazoxymethanol.
AB  - The three-dimensional distribution of neuronal heterotopiae induced in rat brains
      by prenatal exposure to the cytotoxic drug, methylazoxymethanol acetate, has been
      examined by computer reconstruction techniques. Three types of heterotopiae may
      be identified in mature rat brains exposed between E11 and E16: Layer I
      heterotopiae, periventricular heterotopiae, and hippocampal heterotopiae. The
      distributions of Layer I heterotopiae and periventricular heterotopiae show clear
      temporospatial gradients; such that with subsequent age of exposure, Layer I
      heterotopiae are situated progressively more medially, dorsally, and rostrally,
      and periventricular heteotopiae are situated progressively more rostrally.
      Periventricular heterotopiae are most extensive following exposure to the agent
      on E14. For both of these heterotopiae there is a characteristic pattern of
      distribution for each gestational age of exposure to the agent. By contrast,
      hippocampal heterotopiae, consisting of misplaced pyramidal neurons in subfields
      CA1 and CA2 of Ammon's horn, did not show significant changes in distribution
      with different ages of exposure to the drug. The significance of these
      temporospatial gradients for mechanisms underlying the production of the
      heterotopiae is discussed.

PMID- 8302247
TI  - Paternal alcohol exposure and hyperactivity in rat offspring: effects of
      amphetamine.
AB  - Locomotor activity of rat offspring sired by fathers treated with 0, 2 or 3 g/kg
      of alcohol twice daily was assessed at 21, 42 and 90 days of age. Fathers treated
      with the two lower doses were pair-fed to those treated with the highest dose.
      Offspring of nontreated ad-lib fed fathers were also evaluated to determine the
      possible role of paternal stress associated with intubation and pair-feeding. The
      behavioral response to amphetamine was also examined in 90-day-old male
      offspring. Paternal alcohol treatment resulted in increased activity at each age
      for 3 g/kg offspring compared to pair-fed controls. Ad-lib offspring did not
      differ from 0 g/kg controls at 21 and 42 days of age. The significant effect of
      paternal alcohol treatment on offspring activity at 90 days, including a
      significant linear paternal effect, occurred when all amphetamine-treated groups
      were pooled. The alcohol x amphetamine interaction was not significant, but a
      significant linear paternal alcohol x linear amphetamine interaction indicated
      that the paternal alcohol effect on activity was differentially responsive to
      amphetamine. Subsequent analysis of this interaction indicated a significant
      linear paternal alcohol trend only at the high dose of amphetamine. These results
      corroborate a previous report of increased activity on the part of offspring
      sired by fathers treated with alcohol. The presence of a differential effect of
      amphetamine suggests that the paternal effect on activity may be mediated by
      catecholaminergic activity. The absence of significant differences between ad lib
      and 0 g/kg pair-fed controls indicates that paternal stress/undernutrition does
      not significantly affect offspring activity.

PMID- 8302248
TI  - Nurses as "winners" for the President's health care reform package.

PMID- 8302249
TI  - Computer integration into nursing education: the role of the nurse consultant.

PMID- 8302250
TI  - Ethical issues: who decides?

PMID- 8302251
TI  - Nutrition support through the life cycle.

PMID- 8302252
TI  - Pediatric nutrition support.
AB  - Pediatric patients now survive and thrive because of advancements made in
      nutrition support. Growth and development is of paramount importance in this
      population and adequate nutrition is necessary. Growth of premature infants
      receiving nutrition support mirrors intrauterine rates. Survival without
      nutrition support is not always assured because of inadequate nutrient stores.
      Institution of nutrition support in children with chronic illnesses also promotes
      growth and development. Enteral nutrition is preferred because of immunologic
      benefits, lower cost, and less frequent infectious complications. Parenteral
      nutrition should be considered when enteral nutrition fails or is
      contraindicated. Successful nutrition rehabilitation can result if both enteral
      and parenteral nutrition are initiated slowly and advanced as tolerated. Ongoing
      monitoring is essential while promoting "normal" growth and development.

PMID- 8302253
TI  - Nutrition support for the elderly.
AB  - The increasing size and longevity of the geriatric patient population dictates
      that all health care practitioners become more cognizant of the unique
      requirements for nutritional assessment and support of the elderly. This review
      summarizes recent advances in the understanding of the nutrition support needs of
      the old and oldest-old patients requiring enteral or parenteral feeding. When a
      nutrition support formula individualized for the geriatric patient is being
      developed, there is a fine line between excess and deficit, requiring the
      involvement of the entire support team in monitoring the success of feeding.
      Indications for choosing enteral or parenteral feeding are considered excessively
      invasive by some and necessarily "heroic" by others. The patient and his or her
      family should be part of the decision-making process.

PMID- 8302254
TI  - Team treatment of eating disorders.
AB  - The treatment of eating disorders requires the expertise of a multidisciplinary
      team. This case presents the psychologic and physiologic challenges observed in
      managing these patients. Attention must be directed toward the use of techniques
      to obtain a commitment from patients to meet a therapeutic goal. Care must be
      taken to avoid overaggressive feeding of patients with eating disorders to avoid
      the refeeding syndrome.

PMID- 8302255
TI  - Nutrient needs of the preterm infant.
AB  - Preterm infants exhibit special nutrient needs that differ substantially from
      other patient populations. Special characteristics include increased energy and
      protein requirements that must be addressed to prevent tissue catabolism and
      support growth. The immaturity of some organ systems may also complicate the
      administration of nutrition support. This article describes important
      characteristics of enteral and parenteral nutrition as it applies to the preterm
      infant.

PMID- 8302256
TI  - Drug use evaluation approach to monitoring use of total parenteral nutrition: a
      review of criteria for use in cancer patients.
AB  - Monitoring of total parenteral nutrition (TPN) by drug use evaluation appears to
      be a reasonable approach to characterizing use of parenteral nutrition within an
      institution. Development of specific criteria for use of TPN may be difficult
      because of the broad nature of published guidelines. Criteria for use of TPN in
      tumor-bearing patients is controversial. Results from recent investigations
      conflict with previous generally accepted guidelines for providing TPN in cancer
      patients. This article reviews published guidelines for use of TPN as well as
      application of these guidelines for drug use evaluation. Criteria for use of TPN
      and results of a subsequent drug use evaluation in a cancer institution are
      presented.

PMID- 8302257
TI  - How much of what should I order?

PMID- 8302258
TI  - Trace elements in clinical nutrition.
AB  - Although the nearly 20 essential trace elements in humans constitute a small
      fraction of total body weight (less than 4%), the effect of their presence on
      well-being is enormous. Enteral nutrition, whether oral or by tube, is fraught
      with problems that influence nutrient absorption, distribution, metabolism, and
      ultimately, excretion. Parenteral nutrition, although delivered to the
      intravascular milieu, carries with it no guarantee that the trace mineral will
      indeed reach the target site for action. With the questionable nature of dietary
      histories and their unavailability in the setting of relatively emergent
      nutrition therapy, it behooves the clinician to begin complete nutrition and to
      include recommended trace elements early on. The clinician must also be ever
      vigilant about delivering sufficient full-strength commercially available enteral
      formula to provide the recommended dietary allowances of trace minerals.

PMID- 8302259
TI  - Superior mesenteric artery syndrome in a burn patient.
AB  - Weight loss resulting from the hypermetabolic response to burn injury is not
      unusual and is often unavoidable. The loss of retroperitoneal fat has been
      postulated as a major factor in the cause of the uncommon complication of
      superior mesenteric artery syndrome. This syndrome is frequently treated
      nonoperatively with aggressive nutrition support. Nasojejunal feeding past the
      point of obstruction should be considered as the primary method of nutrition
      support. Alternatively, total parenteral nutrition or a combination of enteral
      and parenteral feeding may be necessary to meet nutritional needs until the
      duodenal obstruction resolves. This case study describes the nutrition management
      of a burn patient who developed superior mesenteric artery syndrome.

PMID- 8302260
TI  - Micronutrition in dialysis.
AB  - A variety of dialysis methods are currently used in the treatment of renal
      failure. Nutrition support modalities are also frequently used for patients with
      renal failure who are malnourished or at risk of becoming malnourished. The
      effects of various dialysis methods on certain micronutrient levels and needs
      have generally not been extensively studied, however, this article reviews
      information that has been published regarding carnitine, water soluble vitamin,
      fat soluble vitamin, and trace element levels during dialysis. Recommendations
      for provision of micronutrients during dialysis are provided.

PMID- 8302261
TI  - Molybdenum: an essential trace element.
AB  - Molybdenum is found in most foods, with legumes, dairy products, and meats being
      the richest sources. This metal is considered essential because it is part of a
      complex called molybdenum cofactor that is required for the three mammalian
      enzymes xanthine oxidase (XO), aldehyde oxidase (AO), and sulfite oxidase (SO).
      XO participates in the metabolism of purines, AO catalyzes the conversion of
      aldehydes to acids, and SO is involved in the metabolism of sulfur-containing
      amino acids. Molybdenum deficiency is not found in free-living humans, but
      deficiency is reported in a patient receiving prolonged total parenteral
      nutrition with clinical signs characterized by tachycardia, headache, mental
      disturbances, and coma. The biochemical abnormalities in this acquired molybdenum
      deficiency include very low levels of uric acid in serum and urine (low XO
      activity) and low inorganic sulfate levels in urine (low SO activity). Inborn
      errors of isolated deficiencies of XO, SO, and molybdenum cofactor are described.
      Although XO deficiency is relatively benign, patients with isolated deficiencies
      of SO or molybdenum cofactor exhibit mental retardation, neurologic problems, and
      ocular lens dislocation. These abnormalities seem to be caused by the toxicity of
      sulfite and/or inadequate amounts of inorganic sulfate available for the
      formation of sulfated compounds present in the brain. XO and AO may also
      participate in the inactivation of some toxic substances, inasmuch as studies
      suggest that molybdenum deficiency is a factor in the higher incidence of
      esophageal cancer in populations consuming food grown in molybdenum-poor soil.

PMID- 8302262
TI  - Clinical rounds with nutrition support services. From the Cleveland Clinic. The
      patient is a 55-year-old woman who was admitted September 14, 1989, with
      peritonitis and small-bowel fistulas.

PMID- 8302263
TI  - Receipt of well-baby care--Maine, 1988-1992.
AB  - Routine well-baby care (i.e., nonillness-related visits to a health-care
      professional during infancy) provides important opportunities to promote health
      in infants through timely receipt of recommended vaccinations, detection and
      treatment of diseases, and identification of potential developmental or
      psychosocial disorders.* In Maine, although well-baby services are provided as a
      component of the state's maternal and child health programs, the extent to which
      parents in Maine use public and private sources of such services and adhere to
      American Academy of Pediatrics guidelines has not been well characterized. This
      report uses data from Maine's Pregnancy Risk Assessment Monitoring System (PRAMS)
      to characterize the levels of well-baby care in Maine during 1988-1992.

PMID- 8302264
TI  - Human rabies--Texas and California, 1993.
AB  - During November 1993, two persons, a resident of Texas and a visitor to
      California, died from rabies. This report summarizes epidemiologic and clinical
      information about these cases.

PMID- 8302265
TI  - Imported dengue--United States, 1992.
AB  - Dengue is a mosquito-transmitted acute disease caused by any of four virus
      serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) and characterized by the sudden onset
      of fever, headache, myalgia, rash, nausea, and vomiting. The disease is endemic
      in most tropical areas of the world and can occur in U.S. residents returning
      from international travel. Serum samples from 68 persons with suspected imported
      dengue with onset in 1992 (1) were submitted to CDC from 23 states (Table 1). Of
      these, 17 (25%) cases (from 10 states) were serologically or virologically
      diagnosed as dengue. This report summarizes information about these 17 cases.

PMID- 8302266
TI  - Newly identified hantavirus--Florida, 1994.

PMID- 8302267
TI  - Differential pharmacology of cloned human and mouse B2 bradykinin receptors.
AB  - The pharmacology of cloned B2 bradykinin receptors heterologously expressed in
      cell lines lacking any endogenous bradykinin receptors was analyzed. The
      possibility of B2 bradykinin receptor heterogeneity had been proposed on the
      basis of numerous studies in various tissue preparations. The results reported
      here permit a direct evaluation of some of these hypotheses by examining the
      pharmacological properties of cloned bradykinin receptors. A cloned human B2
      bradykinin receptor was stably transfected into Chinese hamster ovary cells. The
      data suggest that in response to bradykinin (BK), the cloned receptor activates
      both phosphatidylinositol hydrolysis and arachidonic acid release by independent
      pathways. Thus, the activation of these two second messenger pathways does not
      require the existence of two B2 bradykinin receptor subtypes. A mouse gene
      encoding the B2 bradykinin receptor was isolated, and the coding region was
      expressed in COS-7 cells. This murine receptor exhibited the pharmacological
      properties of a "classical" B2 bradykinin receptor. A comparison of the
      pharmacological profiles of cloned human and murine homologs of the B2 bradykinin
      receptor indicates that both receptors bind agonists with similar properties.
      However, the two receptors differ dramatically in their affinity for some peptide
      antagonists. The mouse receptor has a 60- to 80-fold higher affinity for [D
      Arg0Hyp3, Thi5,8,D-Phe7]BK and [D-Arg0,Hyp3,D-Phe7]BK than its human homolog.
      Thus, the species of a bradykinin receptor can have a significant effect on its
      pharmacology. The cloning, expression, and pharmacological comparison of human
      and mouse B2 bradykinin receptor genes indicate that some of the previous reports
      of B2 receptor subtypes can be explained by species differences in a single B2
      bradykinin receptor gene.

PMID- 8302268
TI  - Ethanol stabilizes the open channel state of the Torpedo nicotinic acetylcholine
      receptor.
AB  - Ethanol is known to cause a leftward shift of the acetylcholine concentration
      response curve for channel opening of the nicotinic acetylcholine receptor
      (nAcChoR). However, it remains uncertain whether the mechanism underlying
      ethanol's effect is an increase in the binding affinity of the agonist to the
      receptor or an increase in the open/closed equilibrium for those receptors
      occupied by agonist. In the present study, this question was resolved by
      measuring the efflux of 86Rb+ over 9 msec from Torpedo vesicles after rapid
      mixing with the partial agonist suberyldicholine with or without ethanol as
      appropriate. Suberyldicholine's concentration-response curve is bell-shaped. Two
      actions underlie this bell-shaped curve, namely activation at low concentration
      (apparent dissociation constant for activation, Ka = 38 microM) and self
      inhibition at higher concentration (apparent dissociation constant for
      inhibition, Kb = 9 mM), but the overlap of these two actions only reduces the
      maximum observable flux by 20%. Increasing ethanol concentration from 0 to 0.9 M
      causes: a linear increase in the maximum response of the nAcChoR to
      suberyldicholine from 5 to 80% of the maximum induced by acetylcholine, a
      moderate increase in Ka, and no change in Kb. Analysis of our results using the
      sequential two-site binding model revealed that the main action of ethanol on
      nAcChoR was to increase the fraction of occupied receptors that open. The
      equilibrium constant describing this effect changed by 8-fold at anesthetic
      concentrations. Ethanol also decreased the affinity of suberyldicholine for its
      self-inhibition site by a comparable amount, suggesting that its main action is
      to stabilize the open state. In addition, ethanol caused a small increase in
      suberyldicholine's affinity for the agonist site.

PMID- 8302269
TI  - A G protein-activated K+ current in bovine adrenal chromaffin cells: possible
      regulatory role in exocytosis.
AB  - Guanine nucleotide binding proteins (G proteins) act as signal transducers
      between membrane receptors and ion channels. In the present study, the whole-cell
      arrangement of the patch clamp technique was used to examine the effect of G
      proteins on K+ channels in cultured bovine adrenal chromaffin cells. Internal
      dialysis of chromaffin cells with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma
      S) or external application of AIF-4, to stimulate G proteins, resulted in a
      voltage-dependent increase in the amplitude of the outward K+ currents. The half
      maximal voltage required for activation of the currents was shifted by -16 mV in
      the presence of GTP gamma S. The augmentation in the K+ currents was accompanied
      by the appearance of a fast component of current activation measured at
      potentials positive to 0 mV. The GTP gamma S-sensitive current could not be
      detected when internal K+ was replaced with Cs+ and was reversibly inhibited by
      tetraethylammonium (IC50, 2 mM). In contrast, the scorpion venom charybdotoxin
      (50 nM) and the bee venom apamin (250 nM) only slightly reduced the K+ currents
      during stimulation by GTP gamma S and did not alter the activation kinetics. In
      addition, the GTP gamma S-sensitive K+ current could be activated in the absence
      of internal Ca2+ and when the inward Ca2+ current was inhibited with CdCl2.
      Treatment of the chromaffin cells with fluoride decreased nicotine-evoked
      secretion of catecholamines in a concentration-dependent manner. Thus, bovine
      chromaffin cells contain a G protein-stimulated K+ channel that may play a
      regulatory role in secretagogue-mediated exocytosis.

PMID- 8302270
TI  - Hydrophobic interactions of n-alkyl diamines with the N-methyl-D-aspartate
      receptor: voltage-dependent and -independent blocking sites.
AB  - We examined the block of N-methyl-D-aspartate (NMDA) receptors by n-alkyl
      (straight chain) diamines and related monoamines and triamines using whole-cell
      voltage clamp recording of NMDA receptor currents in cultured rat hippocampal
      neurons and [3H] dizocilpine binding to rat forebrain homogenates. At -60 mV, the
      diamines (carbon chain lengths 3-12) produced a concentration-dependent
      inhibition of NMDA receptor current (IC50 values, 6128-7.3 microM). For diamines
      of carbon chain lengths greater than 6, the inhibition was partially, but not
      completely, relieved by depolarization, indicating that the block occurs at
      distinct voltage-dependent and voltage-independent sites. The block produced by
      short-chain diamines (carbon chain lengths 3-6) was completely relieved by
      depolarization, indicating little or no interaction with the voltage-independent
      site. In comparison with the corresponding diamines, homologous monoamines
      exhibited very low potency, whereas homologous triamines were of equal or lower
      potency. For long-chain diamines, inhibitory potency at both the voltage
      dependent and voltage-independent sites was correlated with carbon chain length
      (binding energy increasing 600-700 cal/mol-CH2), suggesting that binding to each
      of the sites is stabilized by a hydrophobic interaction. Affinities for the
      voltage-dependent blocking site (transformed to 0 mV) and for the voltage
      independent blocking site were similar. These values were also similar to the
      inhibitory potencies of the diamines in the [3H]dizocilpine binding assay.
      Analysis of the voltage-dependence of block at the voltage-dependent site yielded
      z delta values for diamines of intermediate length (carbon chain lengths 7-9)
      that decreased with increasing length from 0.91 to 0.63 [approaching the z delta
      values of monovalent blockers (approximately 0.54) and one-half of the z delta
      values of shorter diamines (approximately 1.1)], suggesting that the intermediate
      length diamines block in a linear, extended chain conformation with one of the
      charges having incomplete access to a deep binding site. Longer chain diamines
      (carbon chain lengths 10 and 12) exhibited larger z delta values (0.78 and 0.98,
      respectively), presumably because enhanced conformational flexibility permitted a
      folded-over conformation. From the interchange distances of the intermediate
      length diamines in their lowest energy conformation, we estimated that the total
      voltage drop within the NMDA receptor channel occurs over a distance of
      approximately 20 A. The putative polyamine facilitatory site antagonist
      diethylenetriamine inhibited NMDA-induced currents at the voltage-dependent site
      (IC50, 654 microM; -60 mV).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8302271
TI  - Pharmacological heterogeneity of the cloned and native human dopamine
      transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding.
AB  - Controversy exists as to whether the functional state of the dopamine (DA)
      transporter is identical to sites mediating the specific binding of selective DA
      transporter radioligands. Therefore, we compared the pharmacological profile of
      numerous dopamine transport substrates and inhibitors on [3H]DA uptake with the
      binding of [3H]WIN 35,428 and [3H]GBR 12,935 to COS-7 cells transiently
      expressing the cloned human DA transporter. [3H]DA uptake and [3H]WIN 35,428
      binding was specific, saturable, and to a single class of binding sites with an
      estimated Km/Vmax of approximately 2 microM and 6 pmol/min/10(5) cells for DA
      uptake and Kd/Bmax values of approximately 10 nM and 113 fmol/10(5) cells for
      [3H]WIN 35,428. [3H]DA uptake was inhibited in a concentration-dependent and
      uniphasic manner by dopaminergic agents with an appropriate rank order of potency
      for the DA transporter. Although most uptake blockers inhibited [3H]WIN 35,428
      binding in a uniphasic manner, WIN 35,428, Lu 19,005, D-amphetamine, and DA
      clearly displayed the presence of both high and low affinity components.
      Comparison of the Ki values for the inhibition of [3H]DA uptake with [3H]WIN
      35,428 binding reveals that, for uptake blockers and D-amphetamine, it is the
      high affinity component that shares pharmacological identity with effects on DA
      uptake (r = 0.9985), whereas for DA it is the low affinity site. In striking
      contrast, however, [3H]GBR 12,935 binding to COS-7 cells could not be made to
      exhibit a pharmacological profile indicative of the DA transporter and suggests
      that the site regulating functional [3H]DA uptake may not be identical with sites
      labeled by [3H]GBR 12,935 in these cells. Moreover, these sites appear unrelated
      to those previously described in native membranes as "piperazine acceptor" or
      P450 proteins. Comparison of Ki values and rank order of potency for the
      inhibition of [3H]WIN 35,428 or [3H]GBR 12,935 binding to human caudate membranes
      reveals pharmacological homology, but not identity, with that of the cloned DA
      uptake process. Taken together, these data suggest that 1) [3H]WIN 35,428
      recognizes two sites of the DA transporter, of which only one appears to
      represent the functional state of the protein, and 2) [3H]WIN 35,428 and [3H]GBR
      12,935 do not appear to bind the same functional form/state of the DA
      transporter. Whether the nonidentity of binding sites is a manifestation of some
      post-translational regulatory event (e.g., phosphorylation/accessory binding
      protein) or caused by the existence of multiple molecular forms of the DA
      transporter is currently unknown.

PMID- 8302272
TI  - Active and inactive enantiomers of 2 beta-carbomethoxy-3 beta-(4
      iodophenyl)tropane: comparison using homogenate binding and single photon
      emission computed tomographic imaging.
AB  - 2 beta-Carbomethoxy-3 beta-(4-iodophenyl)tropane (beta-CIT; also designated RTI
      55) is an analog of cocaine that has been developed as a single photon emission
      computed tomography radiotracer that labels dopamine and serotonin transporters.
      We have prepared the 125I- and 123I-labeled ([1R] "active" and [1S] "inactive")
      enantiomers of beta-CIT. Total homogenate binding of the 125I-labeled inactive
      isomer to baboon caudate and cortex was approximately equal to nonspecific
      binding of the active isomer in cortex and much lower than total binding of the
      active isomer in caudate. However, inactive isomer homogenate binding in caudate
      was somewhat higher than in cortex, and during single photon emission computed
      tomography scanning in vivo striatal (1S)-[123I]beta-CIT uptake was also slightly
      greater than in cortex. Following intravenous administration of the 123I-labeled
      enantiomers, the plasma clearances of the active and inactive enantiomers were
      not significantly different. Single photon emission computed tomography imaging
      demonstrated that a bolus dose of nonradioactive (1R)-beta-CIT rapidly displaced
      the uptake of (1R)-[123I]beta-CIT. In contrast, the brain uptake of (1S)
      [123I]beta-CIT was not displaced by nonradioactive (1R)-beta-CIT using either a
      bolus ("kinetic") or bolus plus constant infusion ("equilibrium") paradigm for
      administration of the radiotracer. In scans with bolus administration of
      radiotracer, peak striatal uptake of the active isomer was approximately twice
      that of the inactive isomer. In comparison to the 123I-labeled active tracer, the
      inactive tracer showed earlier times to peak activity and faster washouts of
      activity in all brain regions. These studies demonstrate beta-CIT
      stereoselectivity using both homogenate binding and in vivo imaging and suggest
      that the inactive enantiomer may be a useful measure of the kinetics of both
      blood-brain barrier transport and nonspecific binding.

PMID- 8302273
TI  - Partial agonist properties of cytisine on neuronal nicotinic receptors containing
      the beta 2 subunit.
AB  - As previously reported by Luetje and Patrick [J. Neurosci. 11:837-845 (1991)],
      the nicotine-like alkaloid cytisine is relatively ineffective in evoking current
      responses from nicotinic receptors containing the beta 2 subunit. In our
      experiments, the responses of alpha 4 beta 2- and alpha 3 beta 2-injected oocytes
      to the application of 1 mM cytisine were only 14.7 +/- 4% and 2.5 +/- 0.8% of the
      responses to 1 mM acetylcholine (ACh), respectively. Concentration-response
      relationships for ACh were examined in the presence and absence of cytisine.
      Although cytisine was relatively ineffective in stimulating current, the
      coapplication of cytisine and ACh reduced the responses to ACh. For alpha 4 beta
      2 receptors, 3 microM cytisine shifted the dose-response curve for ACh to the
      right, resulting in a 60-fold increase in the apparent EC50 for ACh. For alpha 3
      beta 2 receptors, 30 microM cytisine shifted the apparent EC50 for ACh from
      approximately 150 microM to 1 mM. Although the efficacy of cytisine for alpha 3
      beta 2 receptors was very low, cytisine could effectively inhibit the responses
      of these receptors, with an IC50 of approximately 10 microM. The efficacy of
      cytisine for alpha 4 beta 2 receptors was greater than that for alpha 3 beta 2
      receptors, and it was possible to evaluate the partial agonist properties of
      cytisine for these receptors. Although the EC50 of cytisine for stimulating
      current through alpha 4 beta 2 receptors was about 1 microM, concentrations of
      cytisine as low as 20 nM were able to inhibit 50% of the response to 1 microM
      ACh. The inhibitory effects of cytisine were reversible over a period of 5 min.
      Our analysis suggests that cytisine is a true partial agonist for beta 2
      containing ACh receptors and as such can inhibit the response of these receptors
      to ACh through a competitive mechanism. In the case of alpha 4 beta 2 receptors
      cytisine binds with high apparent affinity and low efficacy to a site shared with
      ACh, and for alpha 3 beta 2 receptors both the apparent affinity and efficacy of
      cytisine are relatively low.

PMID- 8302274
TI  - Generation of reactive oxygen intermediates by human liver microsomes in the
      presence of NADPH or NADH.
AB  - Studies were carried out to evaluate the ability of human liver microsomes to
      generate superoxide radical and hydrogen peroxide, and to interact with ferric
      chelates to produce more potent oxidizing species such as the hydroxyl radical
      (.OH). In the presence of either NADPH or NADH, human liver microsomes produced
      superoxide and H2O2 at rates about 20 to 30% of that found with rat liver
      microsomes. These lower rates are caused, in part, by the 3-fold lower content of
      total cytochrome P450 in the human liver microsomes. NADH-dependent rates were
      about 25 to 30% of the NADPH-dependent rates. In the presence of appropriate
      ferric complexes, human liver microsomes generated .OH, promoted cleavage of
      vicinal diols, and underwent lipid peroxidation. In contrast to results with rat
      liver microsomes, NADH-dependent rates of .OH production or lipid peroxidation by
      human liver microsomes were similar to the NADPH-dependent rates. Human liver
      microsomes reduced ferric ATP or ferric EDTA at nearly comparable rates with
      NADPH and NADH. Sensitivity of the various iron-dependent reactions to
      antioxidants was found to be characteristic of the particular system. These
      results suggest the possibility that human liver microsomes are an important
      source of reactive oxygen intermediates, especially under conditions of increased
      NADH or NADPH availability and elevated iron concentration.

PMID- 8302275
TI  - Flunarizine and cinnarizine inhibit mitochondrial complexes I and II: possible
      implication for parkinsonism.
AB  - Cinnarizine and flunarizine are piperazine derivatives with calcium antagonist
      and anticonvulsant properties and are used widely in the treatment of vertigo and
      circulatory disorders. They have been implicated recently in the aggravation, or
      even the induction, of parkinsonism in elderly patients. Because the aetiology of
      parkinsonism has been suggested as having a mitochondrial component, we have
      investigated the effects of both compounds on mitochondrial respiration and on
      the activities of the individual respiratory chain complexes. In intact
      mitochondria from rat liver, both drugs inhibited respiration rates, with
      substrates entering at Complex I (glutamate/malate) and Complex II (succinate).
      These effects could be explained by potent inhibitions (Ki 3-10 microM) of both
      complexes. Complex I is inhibited at a site near the ubiquinone-binding site,
      which is not competitive with respect to ubiquinone, whereas the inhibition of
      Complex II is apparently caused by competition with ubiquinone. Furthermore, the
      inhibition of NADH oxidation by flunarizine in submitochondrial particles caused
      an NADH-dependent generation of superoxide. These inhibitory properties of both
      compounds could be significant factors in the aggravation or induction of
      parkinsonism in elderly patients, in whom mitochondrial function already may be
      impaired.

PMID- 8302277
TI  - Neurites induced by staurosporine in PC12 cells are resistant to colchicine and
      express high levels of tau proteins.
AB  - Staurosporine, a protein kinase inhibitor, induces neurite outgrowth in
      pheochromocytoma cells and, therefore, may serve as a potential prototype for
      neurotropic drugs. The principal aim of the present study was to characterize the
      cytoskeletal properties of neurites induced in pheochromocytoma cells by
      staurosporine, in comparison to those induced by nerve growth factor, with
      emphasis on tubulin and tau proteins. Two major findings are described: a)
      staurosporine rapidly induces outgrowth of neurites that are resistant to
      colchicine treatment; and b) staurosporine treatment causes a rapid increase in
      tau protein levels, with a time course similar to the initiation of its
      neurotropic effects. The following observations exclude tubulin as the cellular
      target for staurosporine action: a) the level, cellular distribution, and
      assembly properties of tubulin are not affected by staurosporine treatment; and
      b) colchicine uptake, its binding to tubulin, and its interference with tubulin
      polymerization are not changed by staurosporine. On the other hand, staurosporine
      treatment causes a transient, dose-dependent increase in tau protein levels. This
      increase, which is already evident after 1 hr, reaches a maximum of 2 to 3 fold
      after 5 hr of treatment and declines to basal level within the next 10 to 15 hr.
      The rapid, transient increase of tau protein levels induced by staurosporine is
      reminiscent of its neurotropic properties. Here we characterize and compare the
      cytoskeletal properties of neurites induced by treatment with staurosporine and
      with nerve growth factor, and we offer a mechanistic explanation for the rapid
      stabilization of staurosporine induced neurites.

PMID- 8302276
TI  - The cloning and expression of an OK cell cDNA encoding a 5-hydroxytryptamine1B
      receptor.
AB  - Serotonin (5-hydroxytryptamine or 5-HT) is an important biogenic amine that
      functions as both a neurotransmitter and a hormone in the central nervous system
      (CNS) and the periphery. We report here the isolation of a cDNA from the OK cell
      that encodes a serotonin receptor (OKc1). When expressed in cultured cells, it
      displayed the pharmacological profile and negative coupling with adenylyl cyclase
      characteristic of a 5-HT1B receptor subtype. Similar to the cloned rodent 5-HT1B
      receptors, it had high affinity for the beta-adrenergic ligand
      [125I]iodocyanopindolol, because of the presence of an asparagine instead of a
      threonine residue in the seventh transmembrane region. The ligands used displayed
      the following rank order of potencies: cyanopindolol > RU24969 > methiothepin >
      serotonin > sumatriptan > methysergide > 8-OH-DPAT > isoproterenol. This profile
      correlates well (r = 0.97) with the native OK cell 5-HT1B receptor. When OKc1 is
      compared to the rat, mouse, and human 5-HT1B receptors, it has an amino acid
      sequence identity of 82%, but it is only 54% identical to the human 5-HT1D
      receptor.

PMID- 8302278
TI  - Heat shock response and cytotoxicity in C6 rat glioma cells: structure-activity
      relationship of different alcohols.
AB  - In C6 rat glioma cells, the n-alcohols methanol, ethanol, propanol, and butanol
      and the aromatic alcohol phenol all induce heat shock proteins (HSPs) of high
      molecular mass (68, 70, 90, and 110 kDa) when applied for 1 hr. The lowest
      alcohol concentrations that induce HSP synthesis cause about 20% cell death, as
      determined by neutral red assay. HSP induction thus occurs at alcohol
      concentrations close to the highest tolerable dose. The cytotoxicity and the
      potential of alcohols to induce the synthesis of HSPs increase with chain length
      and are correlated with the lipophilicity of the alcohols. A clear structure
      activity relationship is observed for both parameters. A calculation of the
      putative membrane concentrations of these alcohols reveals that cytotoxic effects
      (50% cell death) occur at nearly the same membrane concentration (approximately
      0.2 M). This also holds true for the lowest HSP 68-inducing alcohol
      concentrations, but at a lower concentration (approximately 0.12 M). The
      activities of major proteinases are affected by both heat shock and alcohols. The
      effects of alcohols also depend on the lipophilicity of the alcohols. Effective
      concentrations again are close to the highest tolerable dose. The stress
      reactions measured in terms of significant changes in HSP synthesis and
      proteinase activity provide information about the mechanisms by which toxic
      agents act on the cell.

PMID- 8302279
TI  - A recombinant phenobarbital-inducible rat liver UDP-glucuronosyltransferase (UDP
      glucuronosyltransferase 2B1) stably expressed in V79 cells catalyzes the
      glucuronidation of morphine, phenols, and carboxylic acids.
AB  - V79 (Chinese hamster lung fibroblast) cell lines expressing a functional
      recombinant phenobarbital-inducible rat liver UDP-glucuronosyltransferase (UGT),
      i.e., UGT2B1, were established. Western blot analysis of positive colonies, using
      anti-rat liver UGT antibodies, revealed the presence of an immunoreactive
      polypeptide of the expected molecular mass of 52 kDa. The substrate specificity
      of the recombinant enzyme toward > 100 compounds was determined. Phenolic and
      alcoholic substrates included 4-methylumbelliferone, 4-hydroxybiphenyl,
      chloramphenicol, and testosterone, but a range of carboxylic acids of both
      endogenous (medium-chain saturated fatty acids, long-chain polyunsaturated fatty
      acids, and bile acids) and exogenous (profen nonsteroidal anti-inflammatory
      drugs, fibrate hypolipidemic agents, and sodium valproate) origin were also
      accepted, indicating that the enzyme was capable of forming both ether- and ester
      type glucuronides from various structurally unrelated compounds. Determination of
      apparent kinetic constants for the glucuronidation by UGT2B1 of selected
      aglycones revealed a high maximal velocity toward the 3-position of morphine
      (49.3 +/- 2.2 nmol/min/mg of protein), compared with other known substrates such
      as 4-methylumbelliferone (2.67 +/- 0.11 nmol/min/mg of protein) or clofibric acid
      (0.06 +/- 0.02 nmol/min/mg of protein). To gain a better insight into the
      mechanisms underlying the apparently wide substrate specificity of UGT2B1, series
      of structurally related compounds were tested as potential substrates. The rate
      of glucuronidation of unbranched saturated fatty acids and omega,omega,omega
      triphenylalkanoic acids increased progressively with increasing alkyl chain
      length and then declined, with the best substrates in these two homologous series
      being decanoic acid and 4,4,4-triphenylbutanoic acid, respectively.
      Glucuronidation of para-substituted phenols always proceeded at a higher rate
      than that of the corresponding para-substituted benzoic acids. This could mean
      that the aglycon hydroxyl group was better positioned in the enzyme active site
      in the case of phenols. Alternatively, if the initial interaction with the enzyme
      required the aglycon to be in the protonated uncharged form, then the observation
      could be explained by the difference in ionization between phenols and benzoic
      acids at the incubation pH used. The introduction of a bulky alkyl group into the
      para-position led to increases of up to 300-fold in the rate of glucuronidation,
      probably as a result of the increased aglycon lipophilicity. Finally, the enzyme
      showed a degree of stereo- and regiospecificity, preferring (S)-ibuprofen to the
      R-enantiomer (Vmax/Km, 3.06 and 1.10 microliters/min/mg of protein, respectively)
      and glucuronidating lithocholic acid but not hyodeoxycholic acid, which differs
      by only a single hydroxyl group.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8302280
TI  - Activation of heterologously expressed D3 dopamine receptors: comparison with D2
      dopamine receptors.
AB  - Recombinant rat D3 dopamine receptors heterologously expressed in Chinese hamster
      ovary (CHO) cells are functionally coupled to endogenous G proteins. The affinity
      of the receptors for agonists is regulated by guanine nucleotides in the same
      manner as that of other G protein-linked receptors. The magnitude of the change
      in affinity induced by GTP is much less, however, than what is observed for
      recombinant rat D2 receptors expressed in CHO cells at similar densities. The
      striking difference is that the low affinity state (uncoupled D3 receptors) has a
      much higher affinity for agonists than does the low affinity state (uncoupled) of
      D2 receptors. Both receptors in the high affinity state (G protein coupled) have
      similar affinities for dopamine. Three functional responses result from
      activation of D3 or D2 receptors expressed in CHO cells. Both receptor subtypes
      mediate inhibition of adenylyl cyclase activity, increases in extracellular
      acidification rates that are prevented by removal of external Na+ and by
      amiloride analogs, and stimulation of cell division. However, these three
      functional results of D3 and D2 receptor activation are both quantitatively and
      qualitatively different. Dopamine activation of D3 receptors is always 2-5-fold
      less efficacious than dopamine activation of D2 receptors, despite similar
      densities of receptors. Both D3 and D2 receptor-mediated increases in
      extracellular acidification rates are blocked by pertussis toxin; however, the D3
      response and not the D2 response is partially attenuated by membrane-soluble cAMP
      analogs. D3 and D2 receptor-mediated stimulation of mitogenesis is blocked by
      pertussis toxin and unaffected by cAMP analogs. The results show that D2 and D3
      dopamine receptors mediate similar signaling events and are additional examples
      of G protein-linked receptors that can activate more than one pathway. Having
      functionally coupled D2 and D3 receptors expressed in the same cell type enabled
      determinations of agonist potencies at both D2 and D3 receptors. Comparison of
      the potencies at the two receptors reveals that none of the agonists is as
      selective for D3 receptors as was previously thought based on radioligand binding
      data.

PMID- 8302281
TI  - Intramolecular interactions in muscarinic acetylcholine receptors studied with
      chimeric m2/m5 receptors.
AB  - Current models of the three-dimensional structures of muscarinic acetylcholine
      receptors and other G protein-coupled receptors are based primarily on high
      resolution electron diffraction data obtained with bacteriorhodopsin, the
      molecular structure of which is characterized by the presence of seven alpha
      helical transmembrane domains (TM I-VII). However, bacteriorhodopsin does not
      couple to G proteins and its primary sequence lacks a series of amino acids that
      are conserved among virtually all G protein-coupled receptors. Therefore, it
      remains to be shown experimentally whether the molecular structures of these
      functionally different proteins are in fact identical. To address this question,
      we have analyzed the pharmacological properties of a series of hybrid human m2/m5
      muscarinic receptors. Initially, we identified several chimeric constructs that,
      upon transient expression in COS-7 cells, were unable to bind significant amounts
      of the muscarinic antagonists N-[3H]methylscopolamine and [3H]quinuclidinyl
      benzilate. A common structural feature of these constructs was the presence of m2
      receptor sequence in TM VII and of m5 receptor sequence in TM I. The ligand
      binding activity of these "pharmacologically inactive" hybrid receptors could be
      restored by replacing TM I (consisting of m5 receptor sequence) with the
      corresponding m2 receptor domain. These data provide the first direct
      experimental evidence that the molecular architecture of muscarinic receptors
      (and, most likely, that of other G protein-coupled receptors) resembles that of
      bacteriorhodopsin, in that the seven TM helices are arranged in a ring-like
      fashion such that TM I lies directly adjacent to TM VII.

PMID- 8302282
TI  - Continuous spectrofluorometric analysis of formyl peptide receptor ternary
      complex interactions.
AB  - Fluorescent formyl peptides have made it possible to study ligand-receptor-G
      protein (ternary complex) dynamics in real-time, but limitations to sample mixing
      and delivery in flow cytometry have interfered with continuous observation. We
      have taken advantage of the quenching of a fluoresceinated N-formyl pentapeptide
      upon binding to its receptor on permeabilized neutrophils to extend the analysis
      of the ternary complex dynamics to the second time scale. The association and
      dissociation of ligand in the presence and absence of saturating concentrations
      of GTP[S] were examined continuously and the results were found to be in
      agreement with results predicted previously from flow cytometry. We observe
      comparable initial rates for the formation of ligand-receptor (LR) binary
      complexes and ligand-receptor guanine nucleotide binding protein (LRG) ternary
      complexes, dissociation rates differing by two orders of magnitude, and slow
      interconversions between LR and LRG in the absence of guanine nucleotide. When
      fit by the ternary complex model, at least three sides of the model are required
      and the fit is improved if a significant fraction of receptors (RG) are allowed
      to be precoupled to G protein. One of the limitations of the analysis is that
      data fits are insensitive to additional parameters in the calculation which would
      permit analysis of all four sides of the ternary complex model. Experiments
      performed with subsaturating GTP[S] identified coexisting classes of LR and LRG
      and allowed analysis of the altered distribution between coupled and uncoupled
      receptors. At saturating nucleotide levels, the binding of GTP[S] and the breakup
      of the ternary complex occur on a subsecond time frame. This result is consistent
      with the idea that inside a neutrophil where GTP levels are several hundred
      microM, once ternary complex forms, ternary complex decomposition is rapid. Taken
      together, the observed rapid assembly and disassembly of ternary complex account
      for subsecond cell responses to ligand.

PMID- 8302284
TI  - Inhibition of P-type and N-type calcium channels by dopamine receptor
      antagonists.
AB  - P-type Ca2+ channels in cerebellar Purkinje neurons and N-type Ca2+ channels in
      sympathetic neurons were found to be inhibited by D2 dopamine receptor
      antagonists with diverse structures, including phenothiazines (chlorpromazine and
      thioridazine), diphenylbutylpiperidines (fluspirilene and pimozide),
      butyrophenones (haloperidol and spiperone), and a piperazine (fluphenazine).
      Dopamine and quinpirole had no effect on P-type Ca2+ channels. In all cases,
      inhibition was characterized by slow onset and offset. The effects of P-type and
      N-type channels were very similar. Fluspirilene was the most potent of the drugs,
      with EC50 values of 6 microM for P-type current and 2 microM for N-type current.
      Block of P-type channels by fluspirilene was voltage dependent, being enhanced by
      depolarized holding potentials, and use dependent, being enhanced by higher
      stimulation frequencies. The effect of fluspirilene on the P-type Ca2+ channel
      current was not prevented by simultaneous exposure to the peptide toxin omega
      agatoxin IVA, indicating that fluspirilene binds to a distinct site on the
      channel. The results suggest that N-type and P-type Ca2+ channels possess similar
      binding sites for dopamine receptor antagonists and that block of N-type and P
      type channels is relatively weak, compared with that of some T-type and L-type
      Ca2+ channels.

PMID- 8302283
TI  - Conformers of acetylcholinesterase: a mechanism of allosteric control.
AB  - Rate control in acetylcholinesterase (AChE) involves a single anionic site whose
      anionic center controls rate-related biochemical and conformational changes in
      the E (free enzyme) and EA (acylated enzyme) conformers. Change in conformer
      structure and biochemistry affect binding, acylation, and hydrolysis. It is
      significant that the anionic-esteratic intersite distance is not altered during
      conformer change as E is converted to EA. In this enzyme system, cationic
      acetylcholine and anionic AChE are true structural, functional, and biochemical
      counterparts. The anionic center in the E conformer lies at the bottom of a
      sterically restricted, hydrophobic cleft < 8 A wide at the top and > 3 A wide at
      the bottom, while the anionic center in the EA conformer is relatively open. It
      is characterized by a decrease in the relative binding of hydrophobic cations and
      by an ability to bind large organic cations. Binding of acetylcholine, H+, or
      organic cations at the anionic site controls k2(acylation) in the E conformer and
      k3(hydrolysis) in the EA conformer. Acetylcholine binding forms the ES complex in
      which the cation maximizes k2. In the EAS complex, the cation reduces k3 and
      provides allosteric control. Anionic site structure and biochemistry and the
      effect of pH on k2 and k3 differentiates AChE from butyrylcholinesterase. This
      comprehensive study of kinetic and thermodynamic processes in AChE was made
      possible by the synthesis and/or use of families of over 30 cationic and
      acylation probes of known stereochemistry. They act as rulers of the E and EA
      conformers of AChE and provide comparative data on kinetic-based and
      thermodynamic-based constants. Cationic inhibitors affect decarbamylation rates
      in AChE and provide an additional set of comparative data related to the
      mechanism of substrate hydrolysis by AChE. Acridine araphanes are unique neural
      receptor and cholinergic enzyme probes. Their parallel plane and coplanar
      conformations are related to bridge length. Two parallel plane acridine araphanes
      are pure uncompetitive inhibitors of AChE. Scatchard plots of the binding of
      methylacridinium and 9-aminoacridine with the E conformer and 9-aminoacridine
      with the EA conformer indicate binding at a single anionic site. No ternary
      complex (EII or EAII) from two-site binding was detected. In AChE, nonspecific,
      low-level binding at surface ionic and hydrophobic areas is ubiquitous. Binding
      affinity differences greater than two orders of magnitude distinguish binding at
      the anionic site from low level binding at surface moieties. Surface binding
      provides environmental and stability changes in the enzyme but does not modify
      the fundamental biochemistry of the E and EA conformers.

PMID- 8302285
TI  - Isolation and pharmacological characterization of a hamster urinary bladder
      neurokinin A receptor cDNA.
AB  - Functional cDNA clones for hamster neurokinin-2 receptor (NK-2R) were isolated
      from hamster urinary bladder using a polymerase chain reaction-based methodology.
      The hamster NK-2R consists of 384 amino acids with a relative molecular weight of
      43,418. Hamster NK-2R shares significant amino acid sequence homology with other
      tachykinin receptors, particularly with rat, bovine, and human NK-2R (94.3, 84.4,
      and 86.5%, respectively). To examine the pharmacology of cloned hamster NK-2R, we
      transfected mouse erythroleukemia cells with this receptor, prepared high speed
      membranes, and studied the receptor properties utilizing the ligand [4,5-3H
      Leu9]NKA in a receptor-binding assay. For pharmacological comparison, we also
      transfected the human NK-2R into mouse erythroleukemia cells. [3H]NKA bound to
      hamster NK-2R receptor in a protein-dependent, high affinity (Kd1 = 4.14 +/- 0.31
      nM), saturable (Bmax1 = 679 +/- 26 fmol/mg of protein), and highly specific
      manner (89 +/- 2%). A smaller population (10% density) of lower affinity
      receptors (Kd2 = 150 +/- 92 nM), was also observed in competition experiments.
      [3H]NKA bound to the human receptor with significantly higher affinity and
      overall greater receptor density (Kd1 = 0.37 +/- 0.11 nM, Bmax1 = 234 +/- 175
      fmol/mg of protein; Kd2 = 9.0 +/- 2 nM, Bmax2 = 1989 + 990 fmol/mg of protein).
      [3H]NKA binding to both hamster and human receptors was enhanced greatly by
      divalent cations, whereas GTP analogs weakly inhibited binding to hamster
      receptor, but potently inhibited binding to the human receptor. Competition
      experiments with agonists demonstrated binding to high and low affinity states of
      NK-2 receptors, with identical order of potency in hamster or human NK-2R; NKA >
      [Nle10]NKA(4-10) > [beta-Ala8]NKA(4-10) >> substance P >>> Senktide. However,
      remarkable differences were observed in studies with selective NK-2 antagonists
      (hamster, SR48,968 > L659,877 > R396 >> MEN10,376 versus human, SR48,968 >
      MEN10,376 > L659,877 > R396). The rank order of antagonist affinity is consistent
      with the observations of NK-2 receptor pharmacology in the native tissues.

PMID- 8302286
TI  - Conformational and biological studies of neuropeptide Y analogs containing
      structural alterations.
AB  - We evaluated the alpha-helix content, the biological activities and the
      affinities of a series of neuropeptide Y (NPY) analogs containing structural
      alterations, mainly in the central portion of the molecule for which a putative
      alpha-helix arrangement has been proposed. First, we investigated the
      conformational and pharmacological characteristics of derivatives containing the
      N-terminal tetrapeptide linked to C-terminal peptide-amide segments of various
      lengths. In some of these, the missing portion was replaced with epsilon
      aminocaproic acid, a flexible arm-linker. Data revealed that (1-4)-Aca-(18-36)NPY
      is a discontinuous analog almost as potent as the native peptide in a
      pharmacological preparation enriched in Y2 receptors (rat vas deferens), whereas
      it is about 5 times less potent in a Y1 bioassay (rabbit saphenous vein). This
      analog showed a similar profile in [125I]PYY binding assays performed in rat
      frontoparietal cortex (Y1) and hippocampus (Y2) membrane preparations. In a
      series of truncated derivatives obtained with the successive removal of the 5-13
      to 5-17 segments of the NPY molecule, no apparent correlation was observed
      between the affinity or potency in bioassays and the alpha-helix content, as
      measured by circular dichroism spectroscopy. Other truncated analogs, obtained by
      linking the C-terminal 31-36 fragment to various N-terminal tetrapeptides were
      also investigated. None showed any affinity in brain membrane preparations
      (frontoparietal cortex and hippocampus) or activity in the rat vas deferens
      bioassay. However, a weak short-lasting contraction was measured with some of
      these analogs in the rabbit saphenous vein, thus suggesting that the 1-4 and 31
      36 segments of the molecule contains pharmacophores recognized by the Y1 receptor
      subtype. The contribution of the arginine residues also was evaluated in relation
      with the alpha-helix. Their successive substitution with lysine, an excellent
      helix-promoter, showed that the replacement of Arg-19 or Arg-25, two residues
      found in the putative alpha-helix, gave active analogs. Furthermore, the
      substitution of Arg-19 with lysine increased the activity in the rat vas deferens
      as well as the affinity in the brain membrane binding assays. On the other hand,
      the substitution of Arg-33 produced a weak agonist, whereas the replacement of
      Arg-35 generated an inactive analog in the Y2-pharmacological preparation and a
      very weak competitor in the CNS binding assays. Interestingly, this latter analog
      was still active in the rabbit saphenous vein, thus identifying the position 35
      as an additional potential target for the development of Y1 versus Y2 specific
      molecules.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8302287
TI  - Phosphatidylserine synthesis in rat cerebral cortex: effects of hypoxia,
      hypocapnia and development.
AB  - Phosphatidylserine, which is necessary for protein kinase C activity, is
      synthesized in mammalian tissues by the Ca(2+)-dependent base exchange enzyme.
      The synthesis of phosphatidylserine is greater in slices or homogenates of rat
      cerebral cortex subjected to hypoxia by N2 treatment when compared with O2 plus
      5% CO2. An intermediate effect was observed when the treatment was done with N2
      plus 5% CO2. Incorporation rates were dependent on Ca2+ in Krebs-Henseleit Ringer
      bicarbonate medium, being greater with 2 mM Ca2+ than with the same medium
      prepared without Ca2+. The increase of phosphatidylserine synthesis, due to
      hypoxia, was, on the contrary, more evident in the medium lacking added Ca2+.
      Similar results were obtained with the homogenates. This suggests that elevation
      of intracellular Ca2+, caused by hypocapnia and hypoxia, may be responsible for
      the greater incorporation of serine into phosphatidylserine. In both
      cerebrocortical slices and homogenate, [14C]serine incorporation decreased with
      development both in O2 plus 5% CO2 and N2-treated preparations. However, in
      younger rats (14-18 days) hypoxia induced a lesser increase of phosphatidylserine
      than in 40 day old animals. We suggest that a regulatory mechanism for
      phosphatidylserine synthesis is established during development and that N2
      treatment can increase phosphatidylserine synthesis by interfering with this
      regulatory mechanism.

PMID- 8302288
TI  - Accumulation of unsulphated precursors in Dictyostelium discoideum during
      selenate inhibition of growth.
AB  - Incubation of Dictyostelium discoideum cells with selenate is known to inhibit
      vegetative growth. In this paper we show that in the presence of selenate
      macromolecules accumulate which can be converted to sulphated products once the
      selenate is removed. The presence of cycloheximide, an inhibitor of protein
      synthesis, during the subsequent incubation does not prevent this conversion but
      tunicamycin, an inhibitor of glycosylation does. It is concluded that, in the
      presence of selenate, precursors accumulate as unglycosylated proteins,
      suggesting that feedback inhibition of glycosylation may be operated.

PMID- 8302289
TI  - Altered topoisomerase activities may be involved in the regulation of DNA
      supercoiling in aerobic-anaerobic transitions in Escherichia coli.
AB  - This study uncovers a new mechanism of regulation of DNA supercoiling operative
      in vivo upon an aerobic-anaerobic transition in Escherichia coli. Exponentially
      growing aerobic batch cultures were subjected to a shift to anaerobic conditions.
      The ratio [ATP]/[ADP] remained essentially constant at 8.5 in the aerobic culture
      and after a transition to anaerobiosis while DNA supercoiling increased
      noticeably upon anaerobiosis. This result indicated that the mechanism of
      regulation of DNA supercoiling by the [ATP]/[ADP] ratio was not operative. The
      increase in DNA supercoiling was followed by a large decrease in the DNA-relaxing
      activity of topoisomerase I while gyrase activity remained relatively constant.
      This decrease in the activity of topoisomerase I is likely to be responsible for
      the increase in DNA supercoiling.

PMID- 8302290
TI  - Purification and characterization of catalase from goat (Capra capra) lung.
AB  - Catalase plays a major role in the protection of tissues from toxic effects of
      H2O2 and partially reduced oxygen species. In the present study catalase was
      extracted and purified 330-fold from goat lung by acetone fractionation and
      successive chromatographies on DEAE-cellulose, Sephadex G-200, Blue Sepharose CL
      6B and Ultrogel AcA-34. The purified enzyme was almost homogeneous as judged by
      polyacrylamide gel electrophoresis and FPLC. The molecular weight and Stokes'
      radius of the purified enzyme were 339 kDa and 127 +/- 2 A. The enzyme had 11
      sulfhydryl groups and 15 tryptophan groups per mol of the enzyme. A broad pH
      optimum in the range 5.2 to 7.8 was obtained. Sulfhydryl group binding agents,
      thiol reagents and N-Bromosuccinimide inhibited the enzyme activity. The kinetic
      data show no cooperativity between the substrate binding sites. Tryptophan,
      indole acetic acid, cysteine, formaldehyde and sodium azide inhibited the enzyme
      non-competitively with Ki values of 1.5, 1.6, 6.7, 0.55 and 0.0017 mM,
      respectively.

PMID- 8302291
TI  - Features of insulin receptor interaction in placenta from normal, overt and
      poorly controlled gestational diabetic patients.
AB  - Features of insulin binding to trophoblast plasma membranes were studied in six
      normal pregnant women (NP), six overt diabetes (ODP) and six poorly controlled
      glycemic gestational patients (PCDP) i.e. women who did not strictly follow the
      management of diabetes mellitus during pregnancy. A decreased maximum specific
      insulin receptor binding per 0.1 mg membrane protein in placenta from PCDP (12%)
      was found comparing with that from ODP or NP (17.5% and 36.2%, respectively, P <
      0.01), The insulin binding in PCDP declined at a faster rate until it reached
      minimum when studied at a higher temperature (25-37 degrees C). The binding
      equilibrium was likewise attained faster at this temperature than that at lower
      temperature of 4 degrees C for all studied groups. The insulin receptor binding
      in all studied groups was pH dependent. The maximum binding in ODP and PCDP
      groups was attained at pH 7.8 while for NP maximum binding was at pH 7.4. The
      competitive binding assay was carried out with 14 concentrations of unlabelled
      insulin and the half maximal displacement of 125I-insulin was at 8 x 10(-9) M, 6
      x 10(-9) M and 4 x 10(-9) M for NP, ODP and PCDP, respectively (P < 0.05)
      suggesting the differences in the effect of glycemic control on the insulin
      binding. Furthermore the binding yielded curvilinear Scatchard plots with the
      apparent affinity of the receptors being affected in the ODP and PCDP
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302292
TI  - Involvement of carboxyl groups in the divalent cation permeability of rat parotid
      gland basolateral plasma membrane.
AB  - Divalent cation permeability of rat parotid gland basolateral plasma membranes
      was examined in dispersed parotid acini (by Ca2+ or Mn2+ entry) and in isolated
      basolateral plasma membrane vesicles (BLMV, by 45Ca2+ influx). Mn2+ entry (fura2
      quenching) was about 1.6 fold higher in internal Ca2+ pool-depleted acini (Ca(2+)
      depl acini) than in unstimulated cells. Mn2+ entry into Ca(2+)-depl acini was
      increased at external pH > 7.4 and decreased at pH < 7.4. Pretreatment of Ca(2+)
      depl acini with the relatively hydrophobic carboxylic group reagent, N,N'
      dicyclohexylcarbodiimide (DCCD, 50 microM for 30 min) resulted in the inhibition
      of Mn2+ entry into Ca(2+)-depl acini to unstimulated levels. Another hydrophobic
      carboxyl group reagent, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) and
      the relatively hydrophilic carboxyl group reagents, 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC) and 1-cyclohexyl-3-(2
      morpholinoethyl)carbodiimide (CMCD) did not affect Mn2+ entry. Similar to the
      effects in intact acini, Ca2+ influx into BLMV was decreased when the external pH
      was lowered below 7.4. Also DCCD (5 mM, 30 min), but not EEDQ, decreased (40%)
      Ca2+ influx in BLMV. However, unlike in acini, the hydrophilic reagents, EDC,
      EAC, and CMCD decreased Ca2+ permeability in BLMV and the effects were
      nonadditive with the decrease induced by DCCD. The aggregate effects of carboxyl
      group reagents on the Ca2+ and Mn2+ permeability in BLMV and intact acini,
      respectively, suggest that a critical carboxyl group (most likely accessible from
      the cytoplasmic side of the plasma membrane) is involved in divalent cation flux
      in rat parotid acinar cells.

PMID- 8302293
TI  - Studies on the effect of mevinolin (lovastatin) and mevastatin (compactin) on the
      fusion of L6 myoblasts.
AB  - The effect of mevastatin and mevinolin on the fusion of L6 myoblasts was studied.
      Both compounds were present inhibitors of myoblast fusion at concentrations as
      low as 0.25 microM, but fusion was restored when the inhibitors were removed.
      Both compounds resulted in decreased binding of conA and WGA to cell surface
      oligosaccharides showing they were causing a reduction in N-linked cell surface
      glycoproteins. There was a reduction in creatine phosphokinase activities in the
      presence of both compounds showing that they were affecting biochemical
      differentiation. The presence of both compounds inhibited the incorporation of
      labeled mannose from GDP-mannose into lipid-sugar and N-linked glycoprotein, but
      the inhibition was reversed by addition of exogenous dolichol phosphate to the
      incorporation mixture. The main conclusion from these studies is that mevinolin
      and mevastatin are inhibiting myoblast fusion by affecting the synthesis of
      fusogenic cell surface N-linked glycoproteins probably by affecting the synthesis
      of dolichol phosphate containing oligosaccharides that are required as
      intermediates in N-linked glycoprotein biosynthesis.

PMID- 8302295
TI  - Sequence features that correlate with MHC restriction.
AB  - Identification of common sequence motifs in antigenic peptides restricted to a
      specific class II molecule has not been easy due to the large variation in length
      and sequence that is observed in these peptides. The goal of this study is to
      develop an automated computerized method for the identification of sequence
      features and structural determinants that play a role in the MHC restriction of
      helper T-cell antigenic peptides. For this, we compiled an extended database of
      helper T-cell sites, including the information on MHC restriction, when
      available. Two groups of peptides are assigned to each MHC type: (1) peptides
      that bind to that MHC molecule to elicit a T-cell response, and (2) peptides that
      were shown experimentally either not to bind to or not to elicit a T-cell
      proliferative response in association with that MHC molecule. We search for
      common motifs in the group of binding peptides, and identify significant motifs
      that are frequent among these peptides but almost absent in the group of non
      binding peptides. A motif consists of physical-chemical and structural properties
      that may be responsible for binding specificity and can be extracted from
      sequence data, such as, hydrophobicity, charge, hydrogen bonding capability, etc.
      The first search is performed on the non-aligned binding peptides. Next, the
      sequences are aligned according to an identified motif and a search for
      additional, conserved, properties is performed. The statistical significance of
      the motifs is evaluated as well as their compatibility with published
      experimental results on substitution effects. Here we demonstrate the general
      scheme of the analysis and results for I-Ek and I-Ak associated peptides.

PMID- 8302294
TI  - Acetylcholinesterase inhibition by 1-methyl-4-phenylpyridinium ion, a
      bioactivated metabolite of MPTP.
AB  - The effect of the neurotoxicant, 1-methyl-4-phenylpyridinium ion (MPP+) on
      acetylcholinesterase (AchE) activity was investigated. The MPP+ was found to
      inactivate the enzyme in a dose dependent manner. The kinetic parameter, Km for
      the substrate (acetylthiocholine), was found to be 0.216 mM and Ki for MPP+ for
      the inactivation of AChE was found to be 0.197 mM. It was found that MPP+ is
      neither a substrate of AChE nor the time-dependent inactivator. The studies of
      reaction kinetics indicate the inactivation of AChE to be a linear mixed-type
      inhibition. The inactivation of AChE by MPP+ was partially recovered by either
      dilution or gel exclusion chromatography. These data suggest that once MPP+
      enters the basal ganglia of the brain, it can inactivate the AChE and thereby
      increase the acetylcholine level in the basal ganglia, leading to potential cell
      dysfunction. It appears likely that the nigrostriatal toxicity by MPP+ leading to
      Parkinson's disease-like syndrome may, in part, be mediated via the AChE
      inactivation.

PMID- 8302297
TI  - Glycosylation site of the major allergen from olive tree pollen. Allergenic
      implications of the carbohydrate moiety.
AB  - The electrophoretic analysis of purified Ole e I, the major allergen from Olea
      europaea pollen, reveals the presence of two main variants, glycosylated (20.0
      kDa) and non-glycosylated (18.5 kDa) components. The glycosylated variant has
      been identified as a concanavalin A-binding glycoprotein. Its carbohydrate moiety
      has a molecular mass of about 1.3 kDa (5% weight of the glycosylated allergen),
      based on mass spectrometry analysis. Enzymatic treatment of native Ole e I with
      the specific glycosidase PNGase F accounts for an oligosaccharide N-linked to the
      polypeptide chain. This treatment does not sensibly modify the secondary
      structure of the protein but diminishes the affinity of the allergen for specific
      IgE antibodies. Tryptic digestion of Ole e I reveals the presence of a single
      carbohydrate-containing peptide. This peptide was recognized by the sera of
      hypersensitive individuals. The amino acid sequence of this peptide is Phe-Lys
      Leu-Asn-Thr-Val-Asn-Gly-Thr-Thr-Arg, asparagine at the seventh being the
      carbohydrate attaching site. The obtained data are discussed in terms of the
      potential role of the sugar moiety in the allergenic activity of Ole e I.

PMID- 8302296
TI  - Induction of phosphatidylinositol turnover and EGR-1 mRNA expression by
      crosslinking of surface IgM and IgD in the human B cell line B104.
AB  - We have previously shown that a human B lymphoma cell line, B104, expressed
      surface IgM (sIgM) and surface IgD (sIgD), and that crosslinking of sIgM and sIgD
      by anti-IgM antibody (Ab) and anti-IgD Ab, respectively, induced Ca2+ influx to
      almost the same degree, whereas only sIgM-crosslinking caused B104 cell death.
      Here, we investigated the accumulation of cyclic AMP (cAMP), the hydrolysis of
      inositol phosphates, protein kinase C (PKC) activity and the induction of Egr-1
      and c-fos mRNA expression by sIgM- and sIgD-crosslinking to examine differences
      in the signals mediated through sIgM and sIgD in B104 cells. Both sIgM- and sIgD
      crosslinking with antibodies induced elevation of cAMP levels,
      phosphatidylinositol turnover, PKC activation and expression of Egr-1 and c-fos
      mRNA, although sIgM-crosslinking was more effective than sIgD-crosslinking,
      presumably due to the higher expression of sIgM than of sIgD. Egr-1 mRNA
      expression induced by sIgM- and sIgD-crosslinking was inhibited by H7, erbstatin
      and genistein, but not by HA1004. Erbstatin and genistein inhibited the sIg
      crosslinking-induced Egr-1 mRNA expression in a dose-dependent manner parallel to
      that observed in the inhibition of sIg-crosslinking-induced protein tyrosine
      phosphorylation. Phorbol myristate acetate induced Egr-1 mRNA expression but
      forskolin and dibutyryl cyclic AMP did not. These findings suggest that the Egr-1
      mRNA activating signals through sIgM and sIgD are protein tyrosine kinase- and
      PKC-dependent, but protein kinase A-independent. Cyclosporin A (CsA) and FK506
      rescued B104 cells from death induced by anti-IgM Ab, but did not affect the
      expression of Egr-1 and c-fos mRNA, showing that CsA and FK506 affect signal
      transducers differently from or downstream to these molecules. The difference in
      signals transduced through sIgM and sIgD in B104 cells is discussed.

PMID- 8302298
TI  - Functional expression of human CD28 in murine T cell hybridomas.
AB  - CD28 is a 44 kDa Ig superfamily cell surface molecule expressed on most mature T
      cells. Through its interaction with the recently identified B7/BB1 counter
      receptor, it is believed to play an important role as a co-stimulator of T cells
      along with the TCR-CD3 complex. Activation of T cells with CD28 mAbs synergizes
      with TCR-CD3 and CD2 stimulation, resulting in long term T cell proliferation,
      differentiation of cytotoxic T cells and production of large amounts of
      cytokines. In order to further delineate the role of CD28 in signal transduction
      and T cell activation, human CD28 was transfected into CD3+ murine T cell
      hybridomas. High levels of cell surface CD28 expression was achieved by
      protoplast fusion. The transfected molecule retained all the native CD28 mAb
      epitopes found on human T cells. In these transfectants, CD28 mAbs, similarly to
      CD3 mAbs, were able to induce Ca2+ mobilization, IL-2 promoter induction
      (measured as beta-galactosidase activity in T cells hybridomas pre-transfected
      with the IL-2-lac Z reporter gene), IL-2 secretion, TNF alpha production and
      apoptosis (observed as growth arrest and genome fragmentation). The parental host
      cells, or cells transfected with vector alone, responded only to mAbs to CD3. IL
      2 secretion in the transfectants was obtained using either an IgM mAb to CD28 or
      IgG mAbs presented on the surface of IgG-FcR+ B lymphoma cells. Optimal
      activation via CD28 was inhibited by suboptimal concentrations of soluble CD3
      mAb, suggesting an interaction between the two pathways. The immunosuppressive
      drugs Cyclosporin A and FK506 completely blocked CD28 and CD3 mediated IL-2
      production in these transfectants whereas rapamycin had only a partial inhibitory
      effect. Finally, since the transfected human CD28 molecule confers full
      functional responsiveness to the murine T cell hybridomas without the need for
      costimulators such as PMA, this model is ideal for studying the structure
      function relationships of the CD28 molecule as well as the transmembrane and
      cytoplasmic associations implied in CD28 signaling.

PMID- 8302299
TI  - Generation of HLA-B55 restricted T lymphocyte mediated cytotoxicity against
      autologous LCL.
AB  - The lymphocytes of one HLA-A11 positive individual (A1, A11, B49, B55) were
      stimulated in vitro with the autologous EBV transformed lymphoblastoid cell line
      (LCL). The culture contained HLA-A1, A11 and B55 restricted, LCL selective
      cytotoxic T cells (CTLs). In the T cell culture stimulated four times, the lysis
      of A11 and B55 carrying targets suggested that the subsets of the two latter CTL
      types had similar size. After further stimulations the B55 restricted CTLs were
      enriched in the culture. Earlier results suggested that in HLA-A11 positive
      individuals the A11-restricted LCL-selective CTL subset dominates. The
      sensitivity of a target panel including Burkitt lymphoma (BL) lines suggested
      that the peptide presented by the B55 molecule differs in A and B type EBV strain
      carrying cells.

PMID- 8302300
TI  - Characterization of a deletion in the P3 myeloma heavy chain V region sequence in
      the non-secreting cell line NS1.

PMID- 8302301
TI  - Nucleotide sequences of three new members of the mouse V alpha 2 gene family.

PMID- 8302302
TI  - A rationale for monoamine oxidase inhibition as neuroprotective therapy for
      Parkinson's disease.
AB  - Neurons in the substantia nigra may be vulnerable to oxidant stress because (a)
      the metabolism of dopamine generates peroxides, which, in the presence of iron,
      can lead to the formation of the highly reactive hydroxyl free radical; and (b)
      neuromelanin within nigral neurons can bind metals such as iron and aluminum and
      thereby promote the site-specific formation of free radicals. Postmortem studies
      show increased iron, decreased glutathione, and increased lipid peroxidation in
      the substantia nigra of patients with Parkinson's disease (PD). Recent studies
      also report iron and aluminum accumulation within neuromelanin granules of
      patients with PD. These findings suggest that the substantia nigra in the patient
      with PD is in a state of oxidant stress and that antioxidant therapy might
      protect residual dopamine neurons and slow the natural progression of PD.
      Selective inhibitors of monoamine oxidase type B (MAO-B) have been chosen for
      study because of their capacity to interfere with the oxidative metabolism of
      dopamine and so diminish the likelihood that free radicals will be formed.
      Initial studies demonstrate that the MAO-B inhibitor L-deprenyl (selegiline)
      delays the development of disability in otherwise untreated patients with early
      Parkinson's disease. Although the mechanism responsible for these observations
      remains unclear, these results are consistent with the possibility that L
      deprenyl provides neuroprotective effects.

PMID- 8302303
TI  - Neurotoxins and monoamine oxidase inhibition: new aspects.
AB  - Recent clinical studies suggest that selegiline (L-deprenyl) is useful in
      retarding the progress of Parkinson's disease, an effect that may be related to
      its inhibition of monoamine oxidase type B (MAO-B). Selegiline is also reported
      to prevent the toxic effects of the noradrenergic neurotoxin, N-(2-chloroethyl)-N
      ethyl-2-bromobenzylamine (DSP-4). This article reviews recent studies on the role
      of MAO-B and its inhibition in this neuroprotective action of selegiline. Male
      C57Bl/6 mice were given DSP-4 (50 mg/kg) 1 h, 24 h, or 4 days after the
      administration of selegiline (10 mg/kg) or the selective MAO-B inhibitor MDL
      72974 (1.25 mg/kg) and then killed 1 week later for the assay of norepinephrine
      in the hippocampus. The MAO-B-inhibiting effects of selegiline or MDL 72974 were
      also determined after these same intervals. Selegiline and MDL 72974 produced
      comparable degrees of enzyme inhibition 1 h (> 95%), 24 h (> 90%), or 4 days (>
      70%) after their administration. Given 1 h before, selegiline totally blocked the
      norepinephrine-depleting effects of DSP-4, but this protection declined sharply
      when 24 h or 4 days was allowed to elapse between selegiline and DSP-4
      administration. MDL 72974 failed to protect at any time point. In vitro, no
      activity was observed when DSP-4 was used as a substrate for MAO. All of these
      findings suggest that the ability of selegiline to protect against DSP-4-induced
      neuronal degeneration does not depend on its inhibition of MAO-B.

PMID- 8302304
TI  - Selegiline can mediate neuronal rescue rather than neuronal protection.
AB  - Selegiline [(-)-deprenyl] has been reported to slow the progression of disabling
      deficits in Parkinson's disease (PD) and cognitive decline in Alzheimer disease
      (AD). The apparent slowing has been proposed to be based on either symptomatic
      improvement due to increased dopaminergic neurotransmission or alternately on
      protection of neurons from damage caused by toxic oxidative radicals. Both
      mechanisms are hypothesized to result from the inhibition of monoamine oxidase
      type B (MAO-B) activity. Our experiments in two animal models have shown that
      selegiline has a second, previously unsuspected action. That is, selegiline can
      rescue neurons after they have sustained lethal damage and the rescue is
      independent of MAO-B inhibition. It was previously shown that the
      coadministration of selegiline with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) could protect dopaminergic substantia nigra neurons (dSNns) from damage by
      blocking conversion of MPTP to its active radical N-methyl-4-phenylpyridinium
      (MPP+) by inhibiting MAO-B. In the first model, we treated C57BL mice with MPTP
      but delayed selegiline treatment for 72 h after the MPTP treatment to allow for
      complete conversion of MPTP to MPP+ and for maximal dSNn damage by MPP+. The
      delayed selegiline treatment rescued approximately 69% of the dSNns that had not
      died by the time the treatment began but were found to die with saline treatment.
      Selegiline doses that were too small to cause inhibition of MAO-B substrate
      oxidation rescued the MPTP-damaged dSNns. The second model was based on previous
      work showing that immature (14-day-old) rat facial motoneurons die after axotomy
      because of a loss of trophic support from the muscle they innervate. Selegiline
      treatment increased the number of motoneurons surviving axotomy from 24 to 52%,
      showing that selegiline can rescue neurons by partially compensating for the loss
      of target-derived trophic support. This "trophic-like" action of selegiline might
      account for the reported slowing of the progression of PD and AD and suggests
      that selegiline therapy may be of value with acute nervous system damage,
      particularly damage caused by trauma.

PMID- 8302305
TI  - Nigral degeneration in Parkinson's disease.
AB  - Neuronal loss in the substantia nigra of patients with Parkinson's disease (PD)
      does not occur evenly throughout the nucleus: the ventrolateral part of the
      substantia nigra degenerates more severely, whereas the medial part is relatively
      preserved. This pattern of nigral neuronal loss is compatible with the uneven
      loss of dopamine in the striatum (the putamen more affected than the caudate
      nucleus). The predominant loss of ventrolateral nigrostriatal projections in PD,
      leading to substantial loss of dopamine especially in the putamen, is thought to
      contribute to the motor symptoms of the patients. On the other hand, the more
      medial nigral projections may be involved in the cognitive symptoms of patients.
      Selegiline (L-deprenyl) has been shown to delay the need to initiate levodopa
      therapy in early PD, and selegiline has also been suggested to increase the
      survival of PD patients. These observations have led to the proposal of
      selegiline's neuron-saving effect in PD. There is some pathological evidence
      supporting the better survival of nigral neurons in PD patients treated with
      selegiline as compared with those without such treatment. Further studies are,
      however, needed to elucidate this question more clearly.

PMID- 8302306
TI  - Symptomatic effect of selegiline in de novo Parkinsonian patients. The French
      Selegiline Multicenter Trial.
AB  - The French Selegiline Multicenter Trial was carried out in 1990 to investigate
      whether the disability of de novo patients with parkinsonism could be improved
      during the first 3 months by monotherapy with selegiline (10 mg/day). A double
      blind, randomized, placebo-controlled clinical trial was conducted over 3 months
      with 93 patients from 13 centers. Symptomatology was assessed on various disease
      rating scales, including Hoehn and Yahr, Hamilton Depression Rating Scale,
      Unified Parkinson's Disease rating scale, and Schwab and England scores, as well
      as self-assessment. Biological and clinical parameters were measured for
      tolerability, and efficacy was investigated with special reference to the point
      at which therapy with L-dopa had to be started. Selegiline was significantly
      superior to placebo on the various motor rating scores, and depressive scores
      were significantly improved at the end of 3 months. Adverse effects were rare and
      minor. Therefore, selegiline could be the therapy of choice for the treatment of
      de novo parkinsonian patients.

PMID- 8302307
TI  - Selegiline in de novo parkinsonian patients: the Finnish study.
AB  - Selegiline (L-deprenyl) has been recommended as an antiparkinsonian drug to be
      used as an adjunct to therapy with L-dopa, if and when L-dopa starts to lose its
      effect. However, initial selegiline monotherapy followed by L-dopa may be both
      effective and safe. A double-blind, placebo-controlled trial was carried out in
      previously untreated patients with Parkinson's disease randomized to receive
      selegiline (10 mg/day; 27 patients) or placebo (25 patients) until L-dopa
      treatment became imperative. Three rating scales were used for assessment. The
      study design continues to be double-blind even after L-dopa is introduced. L-Dopa
      was needed after 545 +/- 90 days in the selegiline group. This was significantly
      later (p = 0.03) than after placebo (372 +/- 28 days). Disability was less severe
      in the selegiline group, and there were no serious adverse effects. A nearly
      twofold dose of L-dopa was needed in the placebo group to achieve a sufficient
      therapeutic effect during long-term treatment. These results show that selegiline
      is safe and effective as monotherapy in early parkinsonism. It delays the need
      for L-dopa treatment and reduces the amount of daily L-dopa required. This could
      be explained by either a symptomatic effect or neuroprotective efficacy or, more
      likely, a combination of both.

PMID- 8302308
TI  - The relevance of glial monoamine oxidase-B and polyamines to the action of
      selegiline in Parkinson's disease.
AB  - Dopamine and 2-phenylethylamine levels in striatal tissue are known to be
      increased after administration of selegiline (L-deprenyl), but it is still
      difficult to explain why this treatment induces longevity or dopaminergic
      neuroprotection in Parkinson's disease. In the absence of significant polyamine
      or diamine oxidase activities in human brain, polyamines and histamine are
      detoxified by N-acetylation and methylation, respectively. Methylhistamine as
      well as N-acetylated polyamine derivatives are selective substrates for monoamine
      oxidase type B (MAO-B). Theoretically at least, MAO-B inhibition by selegiline
      could result in the increase in the levels of polyamines and their N-acetyl
      derivatives. This could have significance for the action of selegiline in
      Parkinson's disease, as overactive corticostriatal glutaminergic function has
      been implicated in the degeneration of nigrostriatal dopamine neurons, and
      polyamines are potent modulators of the excitotoxic NMDA (N-methyl-D-aspartate)
      glutamate subtype receptor.

PMID- 8302309
TI  - [Lipids from the African swine fever virus].
AB  - The lipids of highly purified african swine fever virus (ASFV) propagated in
      porcine bone marrow cells were observed to contain 25.6% phospholipids, 9.7%
      monoglycerides, 14.1% cholesterol, 17.8% free fatty acids, 14.4% diglycerides,
      13.6% triglycerides, and 6.7% cholesterol ethers. Diethyl ether extracts mono-,
      di-, triglycerides, free fatty acids, 50% of cholesterol and cholesterol ethers,
      and 25% of phospholipids from the virus. Analysis of the 14C-sodiumacetate
      incorporation into viral, cellular and plasmatic membrane lipids has shown that
      (a) different strains of ATV ASFV have identical composition; (b) viral lipid
      composition is determined by lipid composition of the infected cells plasmatic
      membrane; (c) the viral lipid composition is influenced by cells used for
      propagation of the ASFV.

PMID- 8302311
TI  - [High plasmid pBR322 multimerization in Escherichia coli B].
AB  - In bacteria E. coli B (wild) plasmid pBR322 is present as a set of circular
      supercoiled multimers formed of up to 20 head-to-tail linked monomers. The
      highest degree of plasmid multimerization was achieved when the bacteria were
      grown in a mineral-glucose medium based on 0.15 M phosphate buffer (pH 7.5). In
      E. coli K12 grown under similar conditions, plasmid pBR322 was mainly present as
      monomers. A kinetic experiment (initially only monomeric plasmids were present in
      the cells) has shown that multimerization of plasmids occurs step by step, that
      is, by means of interplasmid recombinations. Therefore, in E. coli B the
      efficiency of interplasmid recombinations is higher in comparison with E. coli
      K12. This result reflects some differences between basic systems of genetic
      recombination operating in these two lines of E. coli.

PMID- 8302310
TI  - [A possible mechanism for the endemicity of modern cholera (the role of
      noncultivated forms of Vibrio cholerae 01)].
AB  - The surface water sources of some CIS territories have been screened for cholera
      toxin genes by the polymerase chain reaction. The vct-genes have been found in
      the majority of water samples indicating the presence of noncultivated vibrio
      cholerae cells of an epidemiologic significance. The bacteriological methods
      failed to isolate the active causative agent of cholera. Additional criteria are
      proposed for epidemiological typing of territories for cholera. The absence of
      long deletions or insertions in the vct-genes of noncultivated cholera vibrios
      has been shown in comparison with analogous gene of the active causative agent of
      cholera.

PMID- 8302312
TI  - Quantitation of Bacillus anthracis by using of soybean agglutinin conjugates.
AB  - We examine the possibility of using the soybean agglutinin (SBA) marked by
      peroxidase (HRP), biotin, FITC, or gold in order to determine the number of
      Bacillus anthracis cells of vaccine strain STI. It was shown that the technique
      based on interaction between the lectin and microbial cell walls likely are not
      inferior in sensitivity to traditional ELISA variants. The sensitivities of
      methods were 10(4) cells/ml in the case of SBA-biotin, 10(5) cells/ml in the case
      of SBA-HRP, or 10(6) cells/ml in the cases of SBA-gold and SBA-FITC.

PMID- 8302313
TI  - Multiple hybridization analysis. A simultaneous use of two or three non
      radioactive labels for DNA-probes: biotin, digoxigenin and trans
      diamminedichlorplatinum.

PMID- 8302314
TI  - [Subtractive hybridization--a technique for extracting DNA sequences,
      discriminating between two closely-related genomes].
AB  - This review deals with an analysis of the current status of genomic DNA
      subtraction. The theoretical calculations of kinetics of different ways of
      hybridization are implemented. The main conclusion is that the most preferable
      strategy for such a subtraction is hybridization of single stranded tracer with
      single-stranded driver DNA.

PMID- 8302315
TI  - [Restriction analysis of chromosomal DNA from strains of Salmonella enteritidis].
AB  - Restriction analysis of the chromosomal DNA from 17 Salmonella enteritidis
      strains isolated in Moscow and Novomoskovsk (Tula region) during epidemics and
      sporadically has been undertaken. Restriction profiles of the studied strains
      divide them into five groups differing in physical structure of chromosomal DNA
      which is expressed in the presence of supplementary and more intensively stained
      DNA fragments, possibly, amplified. Restriction analysis is hindered by the
      presence of plasmids in the strains and demands a parallel analysis of the
      plasmid DNA carried by the strain. Lack of coincidence of strain groups obtained
      by different methods demands further investigation to define the real
      significance of the different methods for Salmonella enteritidis typing.

PMID- 8302316
TI  - [Is there a similarity in mechanisms of forming "noncultivated forms" of gram
      negative bacteria and spores in bacilli?].

PMID- 8302317
TI  - Resistance to activated protein C as a basis for venous thrombosis.
AB  - BACKGROUND: In three families with various forms of venous thrombosis, we
      observed an apparently inherited poor response to the anticoagulant activated
      protein C (APC). The condition was due to a deficiency in a previously
      unrecognized anticoagulant factor that functioned as a cofactor to activated
      protein C. METHODS: We conducted the present study to determine the prevalence of
      resistance to APC in patients with venous thrombosis. We compared 104 consecutive
      patients with venous thrombosis confirmed by objective tests with 130 controls.
      In addition, 211 members of 34 families of persons with resistance to APC were
      studied. The anticoagulant response to APC was measured with a modified version
      of the activated partial-thromboplastin time test; the results were expressed as
      APC ratios. RESULTS: Forty-five percent of patients had a family history of
      thrombosis. A significant (P < 0.001) difference in APC ratios was observed
      between the controls and the patients with thrombosis. For 33 percent of
      patients, the APC ratio was below the 5th percentile of the control values,
      although the results of the family studies suggested that the prevalence of APC
      resistance may be even higher (approximately 40 percent) in the patients with
      thrombosis. The inherited nature of the defect was confirmed in a majority of
      cases, and the family studies suggested the mode of inheritance to be autosomal
      dominant. The thrombosis-free survival of APC-resistant family members was
      significantly less than that of non-APC-resistant family members. CONCLUSIONS:
      There was a high prevalence of APC resistance among young persons with a history
      of venous thrombosis, and this resistance appeared to be inherited as an
      autosomal dominant trait.

PMID- 8302318
TI  - Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader
      Willi syndrome plus albinism.
AB  - BACKGROUND: Type II (tyrosinase-positive) oculocutaneous albinism is an autosomal
      recessive disorder that has recently been mapped to chromosome segment 15q11-q13.
      The frequency of this disorder is greatly increased in patients with Prader-Willi
      or Angelman syndrome, both of which involve deletions of chromosome 15q. The P
      protein is a transmembrane polypeptide that may transport small molecules such as
      tyrosine, the precursor of melanin. The P gene is located in chromosome segment
      15q11-q13. METHODS: We studied the tyrosinase and P genes in three patients with
      type II oculocutaneous albinism, one of whom also had Prader-Willi syndrome, and
      in one patient with a milder syndrome known as autosomal recessive ocular
      albinism. Individual exons of these genes were amplified from the DNA of each
      patient by the polymerase chain reaction and screened for mutations by
      simultaneous analyses of single-stranded conformation polymorphisms and
      heteroduplexes and subsequent DNA sequencing. RESULTS: Mutations of the P gene
      were identified in all four patients. These included one frame shift, three
      missense mutations that result in amino acid substitutions, and one mutation that
      affects RNA splicing. The patient with Prader-Willi syndrome plus albinism had a
      typical deletion of the paternal chromosome 15, rendering him hemizygous for a
      maternally inherited mutant allele of the P gene. The child with ocular albinism
      was heterozygous for two different mutations in the P gene. CONCLUSIONS:
      Abnormalities of the P gene are associated with a wide range of clinical
      phenotypes, including type II oculocutaneous albinism, albinism associated with
      the Prader-Willi syndrome, and at least some cases of autosomal recessive ocular
      albinism.

PMID- 8302319
TI  - Brief report: clonal proliferation of type 2 helper T cells in a man with the
      hypereosinophilic syndrome.

PMID- 8302320
TI  - Images in clinical medicine. Coronary atherectomy.

PMID- 8302321
TI  - The economics of dying. The illusion of cost savings at the end of life.

PMID- 8302322
TI  - The influence of the probability of survival on patients' preferences regarding
      cardiopulmonary resuscitation.
AB  - BACKGROUND: Studies suggest that a majority of elderly patients would want to
      undergo cardiopulmonary resuscitation (CPR) if they had a cardiac arrest. Yet few
      studies have examined their preferences after clinicians have informed them about
      the outcomes of CPR. METHODS: To study older patients' preferences regarding CPR,
      we interviewed as many ambulatory patients as possible in one geriatrics practice
      in Denver from August 1, 1991, through July 31, 1992. RESULTS: A total of 371
      patients at least 60 years of age were eligible; 287 completed the interview
      (mean age, 77 years; range, 60 to 99). When asked about their wishes if they had
      cardiac arrest during an acute illness, 41 percent opted for CPR before learning
      the probability of survival to discharge. After learning the probability of
      survival (10 to 17 percent), 22 percent opted for CPR. Only 6 percent of patients
      86 years of age or older opted for CPR under these conditions. When asked about a
      chronic illness in which the life expectancy was less than one year, 11 percent
      of the 287 patients opted for CPR before learning the probability of survival to
      discharge. After learning the probability of survival (0 to 5 percent), 5 percent
      said they would want CPR. CONCLUSIONS: Older patients readily understand
      prognostic information, which influences their preferences with respect to CPR.
      Most do not want to undergo CPR once a clinician explains the probability of
      survival after the procedure.

PMID- 8302323
TI  - Chronic spinal cord injury.
AB  - Spinal cord injuries predispose patients to numerous complications. The care of
      such patients requires attention to multiple bodily systems, sensitivity to the
      effects of interventions on function and lifestyle, and a special vigilance
      because of the tendency of spinal cord injuries to mask problems. Improved
      clinical care, however, has increased the life expectancy of people with spinal
      cord injuries and therefore the prevalence of such injuries. The Americans with
      Disabilities Act should make people with spinal injuries more visible, as they
      participate in and contribute to society in greater numbers. Maintenance of
      health brings greater opportunities for self-care and mobility through
      rehabilitation and may allow people with spinal cord injuries to take advantage
      of future opportunities for neurologic improvement or cure.

PMID- 8302324
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 8-1994. An 84-year-old woman with lymphoma, fever, and pulmonary
      infiltrates.

PMID- 8302325
TI  - Hypercoagulability--a new cofactor in the protein C anticoagulant pathway.

PMID- 8302326
TI  - Prenatal ultrasound screening and perinatal outcome.

PMID- 8302327
TI  - Prenatal ultrasound screening and perinatal outcome.

PMID- 8302328
TI  - Prenatal ultrasound screening and perinatal outcome.

PMID- 8302329
TI  - Deletion and uniparental disomy involving the same maternal chromosome 15.

PMID- 8302330
TI  - Predictors of mortality in patients undergoing hemodialysis.

PMID- 8302331
TI  - A predictive model for non-Hodgkin's lymphoma.

PMID- 8302332
TI  - A predictive model for non-Hodgkin's lymphoma.

PMID- 8302333
TI  - Vena caval obstruction by tumor.

PMID- 8302334
TI  - Vena caval obstruction by tumor.

PMID- 8302336
TI  - Bilateral anterior uveitis: a feature of streptokinase-induced serum sickness.

PMID- 8302335
TI  - Treatment of presumed cerebral toxoplasmosis with azithromycin.

PMID- 8302337
TI  - False positive tests for urinary ketones.

PMID- 8302338
TI  - The prospective payment system and discharge diagnoses for coronary heart
      disease.

PMID- 8302339
TI  - The prospective payment system and discharge diagnoses for coronary heart
      disease.

PMID- 8302340
TI  - A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole
      Study Group.
AB  - BACKGROUND: Amyotrophic lateral sclerosis is a progressive motor neuron disease
      for which there is no adequate treatment. Some research suggests that the
      excitatory amino acid neurotransmitter glutamate may be involved in the
      pathogenesis. METHODS: To evaluate the efficacy and safety of the antiglutamate
      agent riluzole, we conducted a prospective, double-blind, placebo-controlled
      trial in 155 outpatients with amyotrophic lateral sclerosis. The dose of riluzole
      was 100 mg per day. Randomization was stratified according to the site of disease
      onset (the bulbar region or the limbs). The primary end points were survival and
      rates of change in functional status. The main secondary end point was change in
      muscle strength. Analyses were undertaken after 12 months of treatment and at the
      end of the placebo-controlled period (median follow-up, 573 days). RESULTS: After
      12 months, 45 of 78 patients (58 percent) in the placebo group were still alive,
      as compared with 57 of 77 patients (74 percent) in the riluzole group (P =
      0.014). For patients with bulbar-onset disease, one-year survival rates were 35
      percent (6 of 17) with placebo and 73 percent (11 of 15) with riluzole (P =
      0.014), whereas for those with limb-onset disease one-year survival was 64
      percent and 74 percent, respectively (P = 0.17). The survival advantage with
      riluzole was smaller (37 percent [29 of 78] with placebo vs. 49 percent [38 of
      77] with riluzole) at the end of the placebo-controlled period, but it remained
      significant in the overall population (P = 0.046) as well as in the patients with
      bulbar-onset disease (18 percent [3 of 17] vs. 53 percent [8 of 15], P = 0.013).
      The deterioration of muscle strength was significantly slower in the riluzole
      group than in the placebo group (P = 0.028). Adverse reactions to riluzole
      included asthenia, spasticity, and mild elevations in aminotransferase levels.
      Twenty-seven patients in the riluzole group withdrew from the study, as compared
      with 17 in the placebo group. CONCLUSIONS: The antiglutamate agent riluzole
      appears to slow the progression of amyotrophic lateral sclerosis, and it may
      improve survival in patients with disease of bulbar onset.

PMID- 8302341
TI  - Loss of the normal NF1 allele from the bone marrow of children with type 1
      neurofibromatosis and malignant myeloid disorders.
AB  - BACKGROUND: Children with type 1 neurofibromatosis (NF-1) are at increased risk
      for malignant myeloid disorders. Analysis of the NF-1 gene (NF1) suggests that
      the function of its product, neurofibromin, is reduced in affected persons and
      that NF1 belongs to the tumor-suppressor class of recessive cancer genes. This
      model is consistent with evidence that neurofibromin accelerates the intrinsic
      guanosine triphosphate-hydrolyzing activity of the Ras family of regulatory
      proteins. Loss of constitutional heterozygosity has not been reported in the
      benign tumors associated with NF-1, however, and has only been detected in a few
      malignant neural-crest tumors and in some tumor-derived cell lines. METHODS: We
      studied DNA extracted from the bone marrow of 11 children with NF-1 in whom
      malignant myeloid disorders developed and from parental leukocytes. We used a
      series of polymorphic markers within and near NF1 to determine whether
      leukemogenesis was associated with structural alterations of the gene. RESULTS:
      Bone marrow samples from five patients showed loss of heterozygosity. In each
      case, the NF1 allele was inherited from a parent with NF-1 and the normal allele
      was deleted. CONCLUSIONS: These data provide evidence of NF1 may function as a
      tumor-suppressor allele in malignant myeloid diseases in children with NF-1 and
      that neurofibromin is a regulator of ras in early myelopoiesis.

PMID- 8302342
TI  - Brief report: alleviation of systemic manifestations of Castleman's disease by
      monoclonal anti-interleukin-6 antibody.

PMID- 8302343
TI  - Images in clinical medicine. Situs inversus.

PMID- 8302344
TI  - Physician profiling. An analysis of inpatient practice patterns in Florida and
      Oregon.
AB  - BACKGROUND: Physician profiling is a method of cost control that focuses on
      patterns of care instead of on specific clinical decisions. It is one cost
      control method that takes into account physicians' desire to curb the intrusion
      of administrative mechanisms into the clinical encounter. To provide a concrete
      example of profiling, we analyzed the inpatient practice patterns of physicians
      in Florida and Oregon. METHODS: Data for 1991 from Medicare's National Claims
      History File were used to profile 12,720 attending physicians in Florida and 2589
      in Oregon. For each attending physician, we determined the total relative value
      of all physicians' services delivered during each patient's hospital stay.
      Relative value was measured in relative-value units (RVUs), according to the
      resource-based relative-value scale used by Medicare in determining payments to
      physicians. The mean number of RVUs per admission was then adjusted for the
      physician's case mix according to the patients' assigned diagnosis-related
      groups. The influence of the physician's specialty and of selected types of
      services (such as imaging and endoscopy) was also examined. RESULTS: Florida
      physicians used markedly more resources, on average, than their colleagues in
      Oregon (46 vs. 30 case-mix-adjusted RVUs per admission). The difference was
      apparent for all specialties and all types of service. To illustrate the
      profiling data potentially available to the medical staffs of individual
      hospitals, we examined specific data on individual attending physicians and for
      various types of service for three hospitals' staffs. Despite similar overall
      profiles that fell below the national mean, each staff had a different practice
      pattern and would require different efforts to improve efficiency. CONCLUSIONS:
      In an effort to encourage further debate, we have described one method of
      physician profiling. Profiling data help identify and characterize differences in
      practice style to which individual physicians or hospital staffs can respond.
      Because profiling is not based on rigid rules, it is a cost-containment strategy
      that can easily accommodate legitimate exceptions; it is therefore preferable to
      methods in which the appropriateness of each clinical decision is judged
      separately.

PMID- 8302345
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 9-1994. 80-year-old woman with persistent gastrointestinal
      bleeding after right colectomy.

PMID- 8302346
TI  - The use and abuse of practice profiles.

PMID- 8302347
TI  - Riluzole for the treatment of amyotrophic lateral sclerosis--too soon to tell?

PMID- 8302348
TI  - The NF1 gene in myelopoiesis and childhood myelodysplastic syndromes.

PMID- 8302349
TI  - Managed competition and the patient-physician relationship.

PMID- 8302350
TI  - Managed competition and the patient-physician relationship.

PMID- 8302351
TI  - Managed competition and the patient-physician relationship.

PMID- 8302352
TI  - The effect of intensive treatment of diabetes mellitus.

PMID- 8302353
TI  - The effect of intensive treatment of diabetes mellitus.

PMID- 8302354
TI  - The effect of intensive treatment of diabetes mellitus.

PMID- 8302355
TI  - Fat embolism syndrome.

PMID- 8302356
TI  - Fat embolism syndrome.

PMID- 8302357
TI  - Treatment of Parkinson's disease.

PMID- 8302358
TI  - Clinical problem-solving: the pursuit of certainty.

PMID- 8302359
TI  - Donor-type microchimerism associated with graft rejection eight years after liver
      transplantation.

PMID- 8302360
TI  - Social and economic consequences of overweight in adolescence.

PMID- 8302361
TI  - Agarose gel immunodiffusion tests with the addition of PEG (polyethylene glycol
      6000) for the diagnosis and serological follow up of paracoccidioidomycosis
      infection.
AB  - By using PEG (polyethylen glycol 6000) in the gel immunodiffusion tests (ID), the
      precipitin lines were increased in 25.5% of the 192 sera reactions and the titers
      were increased from one to four serial dilutions in 44.6% of the 139 serum
      samples. Owing to its sensitivity, easy interpretation of the results and low
      cost, the use of 2% PEG incorporated into the gel in ID tests is recommended for
      the diagnosis and serological follow-up of paracoccidioidomycosis infections.

PMID- 8302362
TI  - Comparative efficacy of amphotericin B, clotrimazole and itraconazole against
      Aspergillus spp. An in vitro study.
AB  - The susceptibilities of two isolates of Aspergillus flavus, one from a human case
      of recalcitrant mycotic keratitis, and an environmental isolate of A. fumigatus,
      to itraconazole, clotrimazole and amphotericin B were measured. Observations of
      macroscopic growth and microscopic evaluations of conidia germination both
      indicated that the two isolates of A. flavus were markedly more resistant to
      amphotericin B than to itraconazole and clotrimazole. Itraconazole was more
      effective than clotrimazole for all isolates. Our in vitro susceptibility results
      suggest the use of itraconazole should be a primary consideration in the
      treatment of Aspergillus keratitis.

PMID- 8302363
TI  - Modulation of I-A and I-E expression in macrophages by T-suppressor cells induced
      in Cryptococcus neoformans infected rats.
AB  - When the I-A and I-E expressions were assessed in peritoneal macrophages from
      Cryptococcus neoformans infected animals, a significant decrease in the former
      was observed when compared with normal macrophages (p < 0.001) whereas a
      significant increase in the I-E expression was observed when compared with
      controls (p < 0.005). On the other hand, when studying the in vitro action of Ts
      cells on the macrophages, it was observed that the I-A expression was
      significantly reduced in macrophages upon contact with Ts cells. Similar results
      were obtained when Ts cells were replaced by a soluble factor. In contrast, the I
      E expression was significantly increased by in vitro action of the Ts cell or its
      soluble factor. Indomethacin partially restored I-A and I-E expression in the
      macrophages to control levels.

PMID- 8302364
TI  - An experimental model of ascending pyelonephritis due to Candida albicans in
      rats.
AB  - We developed a new experimental model of ascending Candida pyelonephritis in
      female rats with leukopenia and vesicoureteral reflux. Rats were treated
      transperitoneally with cyclophosphamide (200 mg/kg) to induce leukopenia 3 days
      before and transurethrally with diluted acetic acid solution to induce
      vesicoureteral reflux 1 day before inoculation of Candida albicans strain, ATCC
      10259 (containing 10(7) cells). Microscopy revealed acute pyelonephritis in which
      Candida cells invaded from the fornix and/or papilla into the medulla within 3
      days after inoculation. Between 7 and 28 days after inoculation, chronic
      pyelonephritis reached the cortex. The incidence of pyelonephritis increased
      gradually and was approximately 80% after 7 days. Candida colony counts of
      bladder urine specimens obtained by direct puncture were significantly greater in
      rats with pyelonephritis extending into the parenchyma than in those with
      pyelonephritis located along the pelvis (p < 0.01). These results suggest that
      this rat model shows the characteristic feature of ascending pyelonephritis due
      to C. albicans and that the severity of Candida pyelonephritis can be estimated
      from Candida counts of bladder urine.

PMID- 8302365
TI  - A potent specific inhibitor of 6-phosphogluconate dehydrogenase of Cryptococcus
      neoformans and of certain other fungal enzymes.
AB  - A particular lot of the zwitterionic buffer, 2(N-morpholino) ethane sulfonic acid
      (MES), contained a contaminant that inhibited a number of fungal NADP-dependent
      dehydrogenases. Enzymes that were particularly sensitive include 6
      phosphogluconate dehydrogenases from Cryptococcus neoformans and Schizophyllum
      commune and glucose-6-phosphate dehydrogenase from Schizophyllum commune. A
      number of NADP-dependent dehydrogenases of animal origin were tested and all were
      completely insensitive to inhibition except for rat liver 6-phosphogluconate
      dehydrogenase, which was 10-fold less sensitive than the Cryptococcal enzyme. The
      pattern of inhibition in all cases was linear competitive versus NADP. The
      inhibitor has been purified and identified as an ethylenesulfonic acid oligomer.
      This inhibitor holds promise as a model compound for the development of a
      specific antifungal agent.

PMID- 8302366
TI  - Mortality in broiler chicks on feed amended with Fusarium proliferatum culture
      material or with purified fumonisin B1 and moniliformin.
AB  - Two hundred twenty-eight male chicks (Columbia x New Hampshire) were given feed
      amended with autoclaved culture material (CM) of Fusarium proliferatum Containing
      fumonisin B1 (FB1), fumonisin B2 (FB2) and moniliformin in 3 separate feeding
      trials. Purified FB1 and moniliformin were given separately and in combination in
      a fourth feeding trial. Birds were given amended rations at day 1 (Trial 1 and
      4), day 7 (Trial 2), and day 21 (Trial 3) and their respective ration was given
      for 28 days (Trial 1), 21 days (Trial 2), 7 days (Trial 3), and 14 days (Trial
      4). FB1 concentrations were 546, 193, and 61 ppm; FB2 were 98, 38 and 14 ppm; and
      moniliformin were 367, 193, and 66 ppm in the first 3 feeding trial regimens.
      Chicks in Trial 4 were given dietary concentrations of purified FB1 at 274 and
      125 ppm, and moniliformin at 154 and 27 ppm. FB1 and moniliformin, both alone and
      in combination, produced dose-responsive clinical signs, reduced weight gains and
      mortality in chicks. Age of birds given amended feeds had little difference in
      the clinical response; however, those given the rations from days 7 or 21 were
      slightly less susceptible than those given rations beginning at 1 day of age.
      Additive effects were noted when the toxins were given in combination. When
      toxins were given separately, adverse effects took longer to occur. A system to
      monitor pattern and rate of defecation (RD) was developed for assessing the
      chicks' approach to feed, water and heat source as illness progressed. Our
      results indicate that chicks fed corn heavily infected with F. proliferatum under
      field conditions could suffer acute death similar to that described for 'spiking
      mortality syndrome' during the first 3 weeks of age.

PMID- 8302367
TI  - Embryopathic and embryocidal effects of purified fumonisin B1 or Fusarium
      proliferatum culture material extract on chicken embryos.
AB  - One hundred eight fertile eggs (Columbia x New Hampshire) were assigned to 10
      groups of 10 eggs each (2 control groups had 14 eggs each). Five groups of eggs
      were inoculated on day 1 of incubation, while the other 5 groups were inoculated
      on day 10. The inoculum of the 4 treatment groups on both day 1 and 10 consisted
      of 1,10, or 100 microM purified fumonisin B1 (FB1) or a culture material extract
      (CME) of Fusarium proliferatum, having known amounts of FB1, FB2 and moniliformin
      (FB1 20 microM; FB2 4 microM and moniliformin 7 microM). Inoculum consisted of
      the respective toxin(s) dissolved in 100 microliters double distilled, autoclaved
      water (diluent). Control eggs were inoculated with diluent only. Mortality was
      both dose- and time-responsive in all treatments. Eggs inoculated on day 1 with 1
      microM FB1 had 50% mortality; 10 microM FB1 had 70% mortality; 100 microM FB1 had
      100% mortality; and CME had 100% mortality. Eggs inoculated on day 10 with 1,10
      or 100 microM FB1 or CME had 30, 60, 90 and 80% mortality, respectively. Normal
      chicks were hatched from all control eggs. The median death times (MDT50) were
      inversely dose-responsive in all treatments, ranging from 3.0 to 7.4 days in
      embryos exposed on day 1 and from 3.2 to 9.0 days in those exposed on day 10.
      Early embryonic changes in exposed embryos included hydrocephalus, enlarged beaks
      and elongated necks. Pathologic changes were noted in liver, kidneys, heart,
      lungs, musculoskeletal system, intestines, testes and brain toxin-exposed
      embryos.

PMID- 8302369
TI  - Polymer-supported enrichment for the determination of plutonium applied to
      natural waters from the Chernobyl area.

PMID- 8302370
TI  - Doctors vs. lawyers: the debate continues.

PMID- 8302368
TI  - Atherogenesis and fibrinogen: historical perspective and current status.
AB  - A review of 117 research publications describes a deficiency in fatty acid
      transport into intracellular oxidative energy metabolism which causes increased
      fibrinogen synthesis and turnover into fibrin. The increased production of
      fibrin, coupled with depressed activation of plasminogen, increases the
      fibrin/plasmin ratio causing thrombosis-induced atherogenesis. This discovery
      unifies the two schools of atherogenesis based on blood lipid or fibrin
      deposition theories.

PMID- 8302371
TI  - Read me!

PMID- 8302372
TI  - Gold, frankincense, myrrh, and medicine.

PMID- 8302373
TI  - Review of informal interviews and disciplinary actions by the North Carolina
      Board of Medical Examiners, 1988-1991.

PMID- 8302374
TI  - Screening for colon cancer. Is it worth the expense?

PMID- 8302375
TI  - Hospice. Care for the terminally ill.

PMID- 8302376
TI  - Gene Stead looks at doctoring.

PMID- 8302377
TI  - Physicians with good communication skills are made, not born.

PMID- 8302378
TI  - Concurrence of occlusive arteriosclerosis of the lower extremities and coronary
      artery disease. And how a surgeon and son have shared quality time.

PMID- 8302379
TI  - Accessible primary care for Nebraska.

PMID- 8302380
TI  - U.S. Cadet Nurse Corps, 1943-1948, the Nebraska experience.

PMID- 8302381
TI  - A report to the NNA: implementation of the PSDA in Nebraska hospitals.

PMID- 8302382
TI  - If change means opportunity, why do I feel so uneasy?

PMID- 8302383
TI  - The after effects of incest and sexual abuse.

PMID- 8302384
TI  - The Nebraska Rural Nursing Incentive Program--1993.

PMID- 8302386
TI  - Health care reform and the Clinton plan: nursing's perspective.

PMID- 8302385
TI  - "Putting it together: piece by piece, bit by bit". Interview by Sue Bristol.

PMID- 8302387
TI  - RN care is key component to hospital competitiveness.

PMID- 8302388
TI  - Reproducibility of ambulatory intragastric pH monitoring.
AB  - Ambulatory 24-hour intragastric pH monitoring is nowadays the standard technique
      for assessing intragastric acidity. For (patho)physiological and pharmacological
      studies the method has to be sensitive and reproducible. Intragastric acidity was
      measured continuously by means of intragastric electrodes in the gastric corpus.
      In order to assess the reproducibility of the test, we repeated it test twice on
      separate days under standardized conditions in 8 healthy subjects. Subjects were
      fully ambulatory and no medication was administered. We found no significant
      difference between 24-hour median pH values during both study days [1.45 (range
      1.20-1.90) and 1.40 (1.20-2.00), day 1 and 2, respectively]. There was a
      significant overall correlation between consecutive 30-min median pH values
      during 24 hours (r = 0.97, p < 0.0001). Over 24 hours and during the day the
      technique was able to detect consistent pH changes of > 0.1 pH units, but during
      the night only changes of > 0.3 pH units could be detected, due to nocturnal pH
      fluctuations in two subjects. This study shows that ambulatory 24-hour
      intragastric pH monitoring is reproducible and is able to detect small changes in
      gastric acidity.

PMID- 8302389
TI  - The inflammatory abdominal aortic aneurysm. Prevalence, clinical features and
      diagnostic evaluation.
AB  - Eight patients with an inflammatory abdominal aortic aneurysm are described. They
      constituted 3.1% of all aortic aneurysms operated in the period 1981-1990. All
      presented with abdominal complaints and/or backache, and an elevated erythrocyte
      sedimentation rate (ESR); 3 had significant weight loss. The discovery of the
      aneurysm was considered a non-related finding except for 2 patients for whom the
      correct diagnosis was suggested by CT scan. Except for the aortic dilatation, the
      clinical and histopathological features of the inflammatory aneurysm resembled
      those of idiopathic retroperitoneal fibrosis with obstruction of the ureters and
      involvement of the duodenum by extensive perianeurysmal inflammation with
      infiltrates of mononuclear leukocytes and varying degrees of fibrosis. Although
      the triad of abdominal complaints and/or backache, an elevated ESR and weight
      loss has been proposed to suggest the diagnosis, the positive predictive value of
      these parameters was at best 22%. Additional studies, including CT scan, have to
      be performed to exclude, among other factors, vasculitis. Treatment should aim at
      repair of the aneurysm. Resolution of the inflammatory process after operation is
      frequently observed. Immunosuppressive therapy should only be used with caution,
      considering the possible increased risk of rupture.

PMID- 8302390
TI  - Obstructive jejunal adenocarcinoma in the Muir-Torre syndrome.
AB  - A young male patient was referred for endoscopic resection of a recto-sigmoid
      polyp and abdominal complaints. His medical history revealed a sebaceous adenoma
      resection from his back and a tubular adenoma excision from his right upper
      eyelid. After disclosure of a jejunal tumour on a small bowel enema and given the
      remarkable family history characterized by the frequent occurrence of bowel
      cancer, the diagnosis of Muir-Torre syndrome was established. This syndrome
      pertains to the combination of sebaceous gland tumours/adenomas in combination
      with gastrointestinal or genitourinary tract tumours. Inheritance takes place in
      an autosomal dominant manner. It usually occurs in males at an early age. Given
      its low malignancy potential, early detection of the syndrome renders a
      favourable prognosis. Careful examination and follow-up also involving the small
      intestine are mandatory for patients and relatives.

PMID- 8302391
TI  - Necrotizing bronchial aspergillosis in a patient with acute myelocytic leukaemia:
      a case report.
AB  - This case report describes a patient with acute myelocytic leukaemia, who
      developed a necrotizing bronchial aspergillosis. This is an uncommon, new form of
      invasive aspergillosis, which is mainly seen in the heart-lung transplantation
      setting and has only been reported once in another patient with leukaemia.
      Neither amphotericin B nor liposomal amphotericin (AmBisome) was effective. Only
      after the immune system had recovered did the infection disappear.

PMID- 8302392
TI  - Pathophysiology and therapy of heart failure, new insights and developments. Part
      II. Cardiac and peripheral alterations during progressive heart failure.
AB  - The initial phase of heart failure is characterized by peripheral mechanisms such
      as sympathetic stimulation and neuroendocrine activation, which attempt to
      compensate for the decline in cardiac pump function and tissue underperfusion.
      However, the resulting vasoconstriction and sodium and water retention lead to a
      vicious circle wherein the subsequent increase in afterload and in circulating
      volume eventually leads to a further decline in cardiac output, blood pressure
      and tissue perfusion on the one hand, and to systemic and pulmonary congestion on
      the other. Intrinsic cardiac alterations during progressive failure preclude
      efficient cardiac compensation. These alterations include downregulation of the
      beta-receptor, upregulation of its inhibitor subunit (Gi), changes in adenylate
      cyclase and phosphodiesterase activity, depletion of catecholamine stores,
      overexpression of abnormal contractile proteins and inherent changes in ATP-ase
      activity, a derangement of calcium cycling by the sarcoplasmic reticulum, and
      abnormalities in myocardial energy production and transfer. These multiple
      changes underline the importance of the heart per se in heart failure. However,
      it should be realized that the heart failure syndrome depends to a large extent
      on various intrinsic alterations in peripheral tissue function. Renal impairment,
      baroreceptor dysfunction, neuroendocrine activation, abnormalities in skeletal
      muscle metabolism and in vascular control, and electrolyte disturbances all add
      to the overall clinical picture. Both cardiac and peripheral alterations in heart
      failure will markedly affect future diagnostic and therapeutic approaches to this
      syndrome.

PMID- 8302393
TI  - Paracentesis. The importance of optimal ascitic fluid analysis.
AB  - An accumulation of peritoneal fluid can result from a variety of conditions,
      cirrhosis of the liver being responsible for about 75% of all patients with
      ascites. Malignancy accounts for 10-12% and cardiac failure for about 5%. The
      remaining 8-10% of ascites cases have a variety of causes, including
      tuberculosis, pancreatic disease and kidney disease. An early and accurate
      diagnosis often depends on an appropriate ascitic fluid analysis. Patients with
      known liver cirrhosis and clinical deterioration also need to have a
      paracentesis, with a determination of the ascitic fluid leukocyte and neutrophil
      count and adequate bacteriological cultures of their ascitic fluid. The
      diagnostic value of different ascitic fluid parameters and their ability to
      distinguish between several aetiologies and their complications, is discussed.

PMID- 8302394
TI  - The two phases of ischaemic heart disease--when to intervene?

PMID- 8302395
TI  - Effect of cilazapril on glucose tolerance and lipid profile in hypertensive
      patients with non-insulin-dependent diabetes mellitus.
AB  - Hypertension frequently complicates diabetes mellitus and is associated with an
      increased incidence of cardiovascular and microvascular complications.
      Angiotensin-I converting enzyme (ACE) inhibitors are effective antihypertensive
      agents and it has been suggested that they may improve glucose tolerance. We
      performed a double-blind, randomized study comparing treatment for 8 weeks with
      cilazapril, a new ACE inhibitor, or placebo on metabolic variables in 22
      hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients. At week 8
      no significant changes in fasting plasma glucose, fasting plasma insulin,
      haemoglobin A1 and plasma lipids had occurred. The areas under the glucose
      [placebo (mean +/- SD): 10.7 +/- 3.27 and 10.6 +/- 2.53; cilazapril: 11.9 +/-
      3.23 and 12.1 +/- 2.9 mmol/l per 180 min at 0 and 8 weeks, respectively] and
      insulin curve [placebo (median and range): 47.4 (31.4-165.1) and 65.3 (16.8
      190.8); cilazapril: 51.1 (23.8-132.0) and 57.6 (29.0-150.1) mU/l per 180 min at 0
      and 8 weeks, respectively] after a standardized oral liquid test meal were
      unaltered. A significant decrease in mean arterial blood pressure was observed
      after cilazapril (122 +/- 8.6 and 106 +/- 8.3 mmHg at 0 and 8 weeks,
      respectively), in contrast to placebo (122 +/- 6.7 and 120 +/- 6.9 mmHg at 0 and
      8 weeks, respectively). In conclusion, cilazapril does not affect metabolic
      control in hypertensive NIDDM patients, whereas it effectively reduces blood
      pressure.

PMID- 8302396
TI  - Prothrombin fragment 1.2 in both treated and untreated hypertensive patients.
AB  - The coagulation parameters factor VII, fibrin monomers, thrombin-antithrombin III
      (TAT) complexes and fragment 1.2 (F 1.2) were studied in 43 treated and 11
      untreated patients (27 males, 27 females age range 19-70 years) with hypertension
      of moderate severity. The patients included in this study who were treated with
      antihypertensive drugs were still hypertensive in spite of their treatment. The
      median F 1.2 concentrations (interquartile range) in the hypertensive patients
      were more than double those of the reference group: 1.47 (0.79) nmol/l as against
      0.74 (0.49) nmol/l (p < 0.0001). Median concentrations of TAT complexes 2.9 (1.7)
      micrograms/l versus 2.6 (1.6) micrograms/l (p < 0.02) as well as those of fibrin
      monomers 14.2 (4.6) nmol/l as against 10.6 (2.0) nmol/l (p < 0.01) also were
      significantly elevated in the hypertensive patients, but to a lesser extent. For
      factor VII a significant difference was found between males and females. The
      median factor VII value in the male patients was 137% (32%) compared with 100%
      (33%) in the male reference group (p < 0.001). In the hypertensive female
      patients this median value was 147% (36%) in comparison with 139% (60%) in the
      female reference group (p < 0.01). By the Spearman rank test, no correlations
      were found between the coagulation parameters and systolic or diastolic blood
      pressure, age or duration of hypertension. F 1.2 values were correlated with
      fibrin monomers (r = 0.33, p < 0.03) but not with the other coagulation
      parameters studied. The elevated F 1.2 values, together with elevated
      concentrations of TAT complexes and fibrin monomers, are signs of an activated
      coagulation system in these hypertensive patients.

PMID- 8302397
TI  - Erysipelas: not always innocent.
AB  - The case histories of two patients with the "toxic-strep" syndrome are presented.
      This syndrome consists of a Streptococcus pyogenes group A infection, complicated
      by multi-organ failure. In our patients renal failure necessitating haemodialysis
      was present. General characteristics of the syndrome and long-term follow-up are
      presented.

PMID- 8302398
TI  - Lipoid pneumonitis complicating treatment of Hodgkin's disease.
AB  - The development of lipoid pneumonitis (LP) is associated with exposure to
      mineral, animal or vegetable oils through inhalation or local application. We
      report here on a 34-year-old patient with lipoid pneumonitis complicating the
      treatment of Hodgkin's disease. A review of the relevant literature on the
      pathophysiology and diagnosis of LP is provided with emphasis on possible
      mechanisms of development of LP in Hodgkin's disease.

PMID- 8302400
TI  - Diagnosis of pneumonia in mechanically ventilated patients: clinical judgement or
      bronchoscopy?

PMID- 8302399
TI  - Type 2 diabetes mellitus. Aspects of complications and treatment.
AB  - Non-insulin-dependent or type 2 diabetes is a heterogeneous disorder,
      characterized by defects in insulin secretion as well as in insulin action; these
      defects are worsened by the developing hyperglycaemia. Diabetes is an independent
      risk factor for the development of cardiovascular disease. In addition to
      hypertension, which is encountered in almost 50% of patients, lipid
      abnormalities, comprising elevations of both LDL-cholesterol and VLDL
      triglycerides, as well as decreases in the levels of HDL-cholesterol, contribute
      to the high prevalence of vascular disease. Elevated levels of serum
      lipoprotein(a) may add to this increased risk. Considering the apparent
      clustering of risk factors such as poor metabolic control, obesity, hypertension
      and dyslipidaemia, the attainment of optimal blood glucose control forms only one
      of the aims of treatment to prevent the neurological and vascular complications,
      which severely affect the quality of life. Dietary advice comprises the adoption
      of healthy eating habits and reducing the intake of refined sugars and saturated
      fat. The long-term metabolic effects of intensive dietary therapy, however, have
      been disappointing. This necessitates early pharmacological treatment in a
      considerable number of patients. With mild hyperglycaemia, the metabolic effects
      of sulphonylurea and insulin treatment were comparable, but insulin is superior
      to sulphonylurea in patients who are more hyperglycaemic (fasting blood glucose >
      11 mmol/l). In addition to its effects on blood glucose control, insulin therapy
      favourably affects dyslipidaemia. Treatment can be safely instituted on an
      outpatient basis, and hypoglycaemic side-effects are infrequent. Combination
      therapy of insulin and sulphonylurea results in similar metabolic improvement
      when compared with insulin treatment alone, but with a lower dose of insulin and
      the need for only one injection in two-thirds of patients. Drugs such as ACE
      inhibitors, which have no metabolic side-effects, have become the therapy of
      choice when treating hypertension in diabetic patients.

PMID- 8302401
TI  - Relationship between hematocrit and blood pressure: implications for primary
      hypertension.

PMID- 8302402
TI  - Microalbuminuria in insulin-dependent diabetes--strategies to prevent diabetic
      nephropathy.

PMID- 8302403
TI  - Effects of erythropoietin administration on prolactin secretion in normal
      subjects.
AB  - To evaluate the acute effect of human erythropoietin (r-HuEPO) on basal and
      stimulated prolactin (PRL) secretion, 18 normal subjects (12 females, 6 males)
      were studied. The PRL response to thyrotropin-releasing hormone (TRH; 200
      micrograms intravenously, n = 7), metoclopramide (MCP, 20 mg intravenously, n =
      5) and fenfluramine (FF, 60 mg os, n = 6) was tested in presence of saline or r
      HuEPO (30 U/kg intravenously). The drug neither modified basal PRL levels nor
      affected the normal PRL release to TRH, MCP and FF. Our results indicate that, in
      normal subjects, the acute administration of therapeutic doses of r-HuEPO does
      not interfere with PRL secretion both after a direct pituitary stimulus and after
      stimuli involving dopaminergic and serotoninergic pathways.

PMID- 8302404
TI  - Influence of the renin-angiotensin system stimulation on erythropoietin
      production in patients with various forms of arterial hypertension.
AB  - Recent studies suggest the existence of a relationship between the renin
      angiotensin system and erythropoietin (EPO) secretion. It has been studied
      whether patients with various forms of arterial hypertension (essential, renal,
      renovascular, in the course of arteritis) differ with respect to EPO secretion
      and whether EPO serum levels are related to renin response induced by dietary
      sodium restriction to 10-20 mmol Na/24 h for 3 days and upright body position for
      3 h. Patients with different forms of hypertension and normal renal excretory
      function and healthy subjects did not differ in hematocrit value, markers of iron
      metabolism, and EPO secretion except for patients with arteritis who had higher
      ferritin values. In these patients a positive correlation between EPO levels and
      hematocrit values suggests the existence of an altered regulation of EPO
      secretion. In essential hypertension a negative correlation found between changes
      in EPO and PRA levels in response to sodium restriction and upright body position
      may also reflect an altered regulation of both EPO and renin production.

PMID- 8302405
TI  - Erythropoietin treatment and amino acid metabolism in hemodialysis patients.
AB  - A previous report suggests that treatment with recombinant human erythropoietin
      (rH-EPO) significantly improves many abnormalities in circulating amino acids
      (AA) in hemodialysis patients. We evaluated the effects of a 12-month treatment
      with rH-EPO (150-250 U/kg/week) on blood AA levels in 10 patients with chronic
      renal failure under regular dialytic treatment. During treatment, hemoglobin
      levels increased from 7.0 +/- 0.3 to 10.1 +/- 0.3 g/dl at 3 months remaining
      steady thereafter. Before the treatment, patients showed reduced levels of
      essential AA (EAA), mainly valine, leucine and threonine (p < 0.05-0.01); among
      non-EAA (NEAA), aspartate and serine were reduced, whereas glycine, alanine,
      proline, citrulline and cyst(e)ine were increased (p < 0.05-0.001). Val/Gly,
      Ser/Gly and Tyr/Phe ratios were low (p < 0.05-0.01). Total EAA and total NEAA
      (619 +/- 21 and 1,382 +/- 75 mumol/l, respectively, before the study) were
      unchanged (639 +/- 22 and 1,410 +/- 89 mumol/l, respectively) at 12 months.
      Abnormalities in AA levels observed before the treatment persisted throughout the
      study. Only serine increased at the end of the study (p < 0.05). In conclusion,
      contrary to what has been reported, treatment with rH-EPO is not associated with
      an amelioration of AA metabolism in hemodialysis patients.

PMID- 8302406
TI  - Value of urinary endothelin-1 in patients with primary vesicoureteral reflux.
AB  - By using a radioimmunoassay specific for endothelin-1 (ET-1), we measured urinary
      excretion of ET-1-like immunoreactivity (LI) in 63 spot urine samples of 48
      patients with primary vesicoureteral reflux (VUR). And also, urinary excretion of
      N-acetyl-beta-D-glucosaminidase (NAG), beta 2-microglobulin (beta-2-MG),
      microalbumin (Alb) and creatinine (Cr) were measured. There was no significant
      correlation in any of the pairs ET-1 and NAG, ET-1 and beta 2-MG, and ET-1 and
      Alb. Comparing the grade of reflux according to the International Classification
      with urinary ET-1, urinary ET-1/Cr levels in patients with grade 2, 3 and 4 VUR
      were higher than normal, and the ratio of more than normal urinary ET-1/Cr
      increased in proportion to the grade of reflux, but it conversely decreased in
      grade 5. In conclusion, urinary ET-1 may be an indicator of renal tubular injury
      in patients with primary VUR, and its meaning may be different from conventional
      urinary parameters.

PMID- 8302407
TI  - Influence of donor age on cadaver kidney graft function and survival: univariate
      and multivariate analyses.
AB  - The influence of donor age on the outcome of kidney transplantation (TX) was
      evaluated in 169 patients who received a primary cadaver kidney transplant at our
      center between September 16, 1984, and December 31, 1990. All the patients
      received cyclosporin A as part of the immunosuppressive protocol. Patients were
      grouped according to donor age: low donor age (LDA; donor age range 12-25 years),
      medium donor age (MDA; range 26-50 years) and higher donor age (HDA; range 51-66
      years). There were no differences between groups in graft and patient survival,
      and multivariate analysis did not show any effect of donor age on those
      parameters. Proteinuria/day and number of rejection episodes did not differ
      between groups either. Immediate diuresis was more frequent in group LDA than in
      the other two groups (73.8, 54.7 and 57.1%, respectively; p < 0.05) and immediate
      diuresis resulted as a weak positive prognostic factor for graft outcome at
      multivariate analysis (p = 0.05). At both univariate and multivariate analyses,
      donor age resulted inversely correlated with creatinine clearance (CCr) at every
      period after TX but the 5th year, with r2 from 0.12 to 0.23 (p < 0.01). The LDA
      group had significantly better CCr than the HDA group at every period after TX
      but for the 5th year (the MDA group behaved intermediately).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8302408
TI  - Computer algorithm offers a comprehensive view of quantitative bacteriuria.
AB  - Using improved microscopy of urine sediment, the consistent finding of bacteria,
      usually gram-positive cocci at low counts, free or even in casts, in the sediment
      of carefully collected urines from patients with systemic illnesses has led to
      the need to reconsider their exclusion by the customary criteria for
      'significance' of bacteria in urine. Since 'significance' is currently based upon
      mathematical assumptions limited to high counts (> 10(5) colony-forming units/ml)
      for the prediction of clinical pyelonephritis alone, a digital computer program
      was created to predict the full spectrum of the expected concentration of
      bacteria in bladder urine versus time for a very wide range of possible bacterial
      division times, bladder kinetics and urine flow rates. Curves generated resulted
      in the discovery of very simple rules based on an easily calculated discriminant,
      the host's critical division time (CDT) for any bacterial species in his urine.
      (1) If the division time in the urine of a species entering the urinary tract is
      shorter than the CDT, the bacteria will proliferate to > 10(5) cfu/ml. Published
      data on growth in human urine show that very few bacterial species can divide so
      fast in urine, and those are the ones currently considered 'significant'. Except
      for some enterococci, streptococci cannot. (2) With a division time only
      marginally longer than the CDT, any bacterium would wash out unless continuously
      supplemented via the kidney or from the bladder wall. (3) With a continued
      supplement and the longer division time, the concentration would fall to a low
      plateau, and that plateau is diagnostic of a continued supplement. The cocci
      observed by microscopy are fastidious or dead. They grow poorly if at all in
      urine, and thus are not likely to ascend the urinary tract. Their appearance
      corresponds to the earlier studies of bacteriuria and to the known excretion of
      blood-borne bacteria in natural disease, whether or not there are anatomical
      changes in the kidney. It is suggested that the low-level coccal bacteriuria
      found is a marker for scent bacteremia in many systemic diseases for which a
      bacterial provocation has been sought.

PMID- 8302409
TI  - Dialysis-associated arthropathy: secondary ion mass spectrometry evidence of
      aluminum silicate in beta 2-microglobulin amyloid synovial tissue and articular
      cartilage.
AB  - The role of aluminum accumulation in articular tissues of patients affected by
      dialysis-associated arthropathy (DAA) is questioned. The aim of this work is to
      identify the nature of these aluminum accumulations by the use of secondary ion
      mass spectrometry (SIMS). Al/Si ratios of about 1, measured by SIMS, strongly
      suggest for the first time the presence of aluminum silicates and possibly
      aluminum hydroxides in amyloid synovial tissue and articular cartilage of 1
      patient with DAA and aluminum intoxication. This is thermodynamically consistent
      with the total dissolved Al and Si contents and pH measured in the synovial
      fluids. These results are similar to the abnormal Al distribution recently found
      by SIMS in the forebrain of chronic renal dialysis patients and to the amorphous
      aluminum silicates identified in the core of senile plaques in Alzheimer's
      disease.

PMID- 8302410
TI  - Urinary glycosaminoglycans in different phases of Balkan endemic nephropathy.
AB  - The relationship between glycosaminoglycans and beta 2-microglobulin,
      glycosaminoglycans and N-acetyl-beta-D-glucosaminidase as well as the
      relationship between the chondroitin sulfate/heparan sulfate ratio and SDS
      electrophoresis in the urine of subjects from the endemic area of Balkan
      nephropathy was studied in order to establish a method for early detection of
      this disease. The results show an unquestionable increase in urinary excretion of
      total glycosaminoglycans in subjects with or suspected of having Balkan endemic
      nephropathy while the chondroitin sulfate/heparan sulfate ratio was not
      statistically different between the groups studied. Thus, the chondroitin
      sulfate/heparan sulfate ratio cannot be used as a cheap and quick
      semiquantitative method for the diagnosis of early tubular damage in Balkan
      endemic nephropathy. However, the determination of total glycosaminoglycans in
      the urine of subjects from endemic areas proved to be valuable additional
      information helping with the diagnosis of Balkan endemic nephropathy.

PMID- 8302411
TI  - Assessment of the thyroid function of patients undergoing regular haemodialysis.
AB  - Thyroid function has been assessed in 36 clinically euthyroid patients undergoing
      regular haemodialysis. The influence of erythropoietin administration on the
      thyroid function tests has been determined. Thyroid-stimulating hormone (TSH) has
      been found to be elevated in 8% of the patients. Free tri-iodothyronine was below
      the normal range in 67% of the population. Free thyroxine (FT4) was low in 67% of
      the patients when tested by an analogue method. FT4 tested by a 2-stage method in
      a subgroup of 22 patients was abnormally low in only 23% of the patients.
      Erythropoietin did not seem to improve these thyroid abnormalities despite a
      partial correction of the anaemia. A rise in FT4 was also observed after
      haemodialysis without a concomitant change in TSH concentration. This FT4
      elevation was attributed to the effect of heparin.

PMID- 8302412
TI  - Effect of high-flux hemodialysis on cardiac structure and function among patients
      with end-stage renal failure.
AB  - The effect of high flux hemodialysis on left ventricular function in ESRD
      patients was evaluated in a double blind, single cross-over, study comparing
      conventional to high flux hemodialysis. The subjects were 21 stable chronic
      hemodialysis patients. Ten were randomly allocated to the conventional-high flux
      sequence and 11 to the reverse sequence. The conventional membrane was the CD
      3,500 or 4,000; the high flux membrane was the Duoflux (Althin Medical Inc.,
      Miami Lakes, Fla.). Both were cellulose acetate and both were sterilized with
      ethylene oxide. The dialysate bicarbonate and sodium were held constant for the
      study. The ultrafiltration rates were 3.5-5.0 ml/h/mm Hg transmembrane pressure
      for the conventional and 15 ml/h/mm for the high flux membrane. The beta-2
      microglobulin sieving coefficient was 0 for conventional and 0.27 for the high
      flux membrane. The modest improvements in estimates of systolic function suggest
      a cardiac advantage in high-flux dialysis, the clinical impact of which requires
      further study.

PMID- 8302413
TI  - Renal hypouricemia due to enhanced tubular secretion of urate associated with
      urolithiasis: successful treatment of urolithiasis by alkalization of urine K+,
      Na(+)-citrate.
AB  - We encountered a case of hypouricemia with increases both in urate clearance
      (Cur) and in the ratio of Cur to creatinine clearance (Cur/Ccr), the normal daily
      urinary excretion of urate, and urolithiasis. Pyrazinamide markedly decreased Cur
      and Cur/Ccr, and both probenecid and benzbromarone markedly increased Cur and
      Cur/Ccr, however, benzbromarone did not increase either Cur or Cur/Ccr under
      pretreatment with pyrazinamide in the patient. Thus, the diagnosis was made of
      renal hypouricemia due to enhanced tubular secretion of urate. The urinary pH of
      the patient tended to be acidic. Three months after the start of alkalization of
      the patient's urine by K+, Na(+)-citrate, both urolithiasis and the symptoms
      related to urolithiasis disappeared. These results suggest that renal
      hypouricemia due to enhanced tubular secretion of urate can result in
      urolithiasis and the alkalization of urine may be an effective treatment for uric
      acid stones.

PMID- 8302414
TI  - Pharmacoeconomic comparison of cyclosporine oral solution and capsules after
      kidney transplantation.
AB  - We studied 20 kidney transplant recipients who had received Sandimmune
      cyclosporine A (CSA) capsules for an average of 7.9 months at a mean dose of 312
      mg/day. They were switched to CSA liquid in the same dosage for an average of
      15.5 months. There was no significant difference between the means for the
      monthly values of either serum creatinine or whole blood CSA when the periods on
      capsules and liquid were compared. Fourteen bottles from 4 batches with volume
      stated as 50 ml CSA actually contained an average of 53.7 ml. Comparison of the
      amount of capsules and liquid CSA prescribed and the amount dispensed by the
      pharmacy showed that the amount neglected (prescribed > dispensed) was similar
      for patients on liquid and capsules. Wastage (prescribed < dispensed) was about
      5% greater when on liquid, and as our cost for liquid was 18% less than for
      capsules, we saved about 13% by use of the liquid.

PMID- 8302415
TI  - Study of glomerular permselectivity for proteins of the glomerular basement
      membrane using a dialyzer model.
AB  - The glomerular basement membrane (GBM) is considered to regulate glomerular
      permselectivity for proteins by acting as both size barrier and charge barrier.
      Since heparan sulfate-proteoglycan (HS-PG), which forms the charge barrier of
      GBM, contains a sulfonic acid, we made membranes with various degrees of negative
      charge models of GBM by addition of sulfonic acid to ethylene vinyl alcohol
      (EVAL) membranes. A high-resolution scanning electron-microscopic study revealed
      no ultrastructural alterations after adding sulfonic acid to EVAL membranes. Both
      neutrally and negatively charged membranes had porous structures in the inner
      surface of the membranes. The interrelation between the two actions of size and
      charge of GBM was studied using special dialyzers with various degrees of
      negative charge and different pore sizes. The negatively charged membranes
      adsorbed proteins with positive charge and repulsed proteins with negative
      charge. The degrees of adsorption and repulsion were weaker in membranes with
      larger pores and were stronger for proteins with larger molecular weights. The
      permselectivity for proteins of a charged membrane depends largely upon the
      interrelation between the pore size of the membrane and the size of the proteins.
      It is, therefore, suggested that the presence of a size barrier in GBM is
      necessary for the charge barrier to effectively exert glomerular permselectivity
      for proteins. Our study may lead to the development of a dialyzer with higher
      permselectivity by adding sulfonic acid rather than conventional dialyzers.

PMID- 8302416
TI  - Inhibitory effect of tannin in green tea on the proliferation of mesangial cells.
AB  - The effect of green tea tannin on the proliferation of mesangial cells was
      determined in terms of [3H]thymidine uptake. When green tea tannin was added to
      the medium of mesangial cell cultures, it suppressed the proliferation of
      mesangial cells markedly. In particular, (-)-epigallocatechin 3-O-gallate, the
      predominant component of the green tea tannin mixture, exerted an inhibitory
      effect at a relatively low concentration, suggesting a direct corroboration of
      the renal effects.

PMID- 8302417
TI  - Erythropoietin increases blood pressure in normotensive and hypertensive rats.
AB  - Treatment with recombinant human erythropoietin (rHuEPO) successfully reverses
      anemia in uremic patients. Of major concern, however, are blood pressure
      increases during rHuEPO therapy, observed particularly in patients with a history
      of hypertension. The present study was designed to determine whether high-dose
      rHuEPO elevates blood pressure in nonuremic rats, and if so, whether preexisting
      hypertension enhances this response. We examined blood pressure responses to high
      (100 IU/kg) and very high (200 IU/kg) doses of rHuEPO or placebo, given
      subcutaneously every other day for 3 weeks to male spontaneously hypertensive
      rats (SHR) and their normotensive genetic controls (Wistar-Kyoto rats, WKY). The
      high and very high doses of rHuEPO stimulated equivalent increases in hematocrit,
      and this increase was always larger in SHR than in WKY. In contrast to the
      pattern of hematocrit changes, blood pressure did not change following high-dose
      rHuEPO but was elevated in both strains after the very high dose of the drug.
      Although the rise in blood pressure tended to be greater in SHR than in WKY, this
      difference was not significant. The data indicate that very high-dose rHuEPO
      raises blood pressure comparably in normotensive and hypertensive rats and this
      increase is relatively independent of the increase in hematocrit.

PMID- 8302418
TI  - Study on impaired metabolism of guanidinoacetic acid in chronic renal failure
      rabbits with special reference to impaired conversion of arginine to
      guanidinoacetic acid.
AB  - Most chronic renal failure (CRF) patients show low serum concentrations of
      guanidinoacetic acid (GAA). In this study, the author investigated the impaired
      metabolism of GAA in CRF focusing on the transformation of arginine (Arg) to GAA
      by analyzing CRF rabbits using 14C-Arg. The CRF group which consisted of 6 CRF
      rabbits, was compared with 6 normal rabbits (normal group). Blood samples were
      obtained from each abdominal aorta after a bolus injection of 30 mu Ci of 14C-Arg
      into an ear vein of each rabbit. After the last sampling, the left kidney was
      obtained for measurement of renal glycine amidinotransferase (GAT) activity. In
      each blood sample, the concentrations of blood urea nitrogen (BUN), serum
      creatinine (Cr), GAA and Arg were measured. The radioactivity of serum 14C-GAA
      was measured with a liquid scintillation system. delta 14C-GAA was calculated as
      the difference between the 14C-GAA count and the 14C-background count. Serum
      concentrations of GAA and renal GAT activity were significantly lower in the CRF
      group as compared with the normal group. Significant negative correlations were
      found between the two groups for the following comparisons: serum concentrations
      of Cr and GAA, concentrations of BUN and renal GAT activity, and serum
      concentrations of Cr and renal GAT activity. There was a significant positive
      correlation in the two groups, between renal GAT activity and serum
      concentrations of GAA. The fact that the concentrations of neither GAA nor Arg
      changed significantly after the injection of 14C-Arg in either group suggested
      that the dosage of injected Arg is not sufficient to affect the transformation of
      Arg to GAA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302419
TI  - Increase in renal and urinary low and high molecular weight kininogens during
      chromate-induced acute renal failure in the rat: evidence for renal kininogen
      production.
AB  - In the present study, we investigated the plasma, urinary and intrarenal
      concentrations of low and high molecular weight kininogens during sodium chromate
      (25 mg/kg body weight)-induced acute renal failure (ARF) in the rat. Urinary
      kininogen underwent a transient increase with a maximum on day 7 (78 +/- 22
      versus 4.2 +/- 1.6 ng bradykinin/mg creatinine) whereas plasma kininogen did not
      and glomerular filtration rate decreased (92 +/- 8 versus 895 +/- 70
      microliters/min). The tissue level of kininogen was enhanced both in the cortex
      (1,319 +/- 123 versus 86 +/- 8 pg bradykinin Eq/mg protein) and in the medulla
      (1,673 +/- 138 versus 44 +/- 9 pg bradykinin Eq/mg protein) but more in the
      medulla (36 +/- 4- versus 15 +/- 3-fold). As plasma kininogen level was unchanged
      and glomerular filtration rate decreased, the increase in both renal
      concentration and urinary excretion of kininogen probably reflects stimulated
      renal production of kininogen in this model of ARF. Whether the evoked renal
      production of kininogen results from a local inflammatory response only or may
      subserve another physiological purpose remains to be elucidated.

PMID- 8302420
TI  - Chronic caffeine ingestion exacerbates 2-kidney, 1-clip hypertension and
      ameliorates deoxycorticosterone acetate-salt hypertension in rats.
AB  - The present study was aimed to determine the effect of caffeine on the
      development of renal hypertension. Two-kidney, 1-clip (2K1C) hypertension and
      deoxycorticosterone acetate (DOCA, 200 mg/kg, subcutaneous implantation)-salt
      (0.9% NaCl drinking) hypertension were instituted in Sprague-Dawley rats. They
      were then grouped into two groups each: one was supplemented with caffeine (0.1%)
      in their drinking solution and the other was not. Systolic blood pressure was
      measured up to 24 days. Caffeine exacerbated the development of 2K1C hypertension
      in association with a higher plasma renin concentration (PRC). Caffeine
      ingestion, however, did not exacerbate but ameliorated DOCA-salt hypertension in
      which PRC was comparable between the caffeine-ingested and control groups.
      Concentrations of plasma atrial natriuretic peptide (pANP) were significantly
      different between the caffeine-ingested and control groups neither in 2K1C nor in
      DOCA-salt rats, suggesting that ANP was not responsible for the modified blood
      pressure. Acute caffeine infusion (350 micrograms/min, 30 min) in anesthetized
      normotensive rats caused increases in urinary excretion (volume and sodium) and
      in PRC without significantly affecting the blood pressure and pANP. These results
      suggest that caffeine specifically exacerbates 2K1C hypertension through
      increasing renin release whereas it ameliorates DOCA-salt hypertension possibly
      through increasing renal excretion.

PMID- 8302421
TI  - Mechanism of polyuria after cisplatin therapy.
AB  - Cisplatin is an antineoplastic agent. Several nephrotoxic effects are associated
      with its use including chronic and acute renal failure, renal magnesium wasting,
      and polyuria. We have investigated polyuria in groups of rats treated with
      cisplatin at doses of 2.5 and 5 mg/kg body weight given once weekly for 3 weeks
      to determine possible mechanisms of this impairment. After cisplatin
      administration, glomerular filtration rate was reduced and significant increases
      in sodium and water loss were also seen. These changes were associated with
      decreases in urinary cAMP. Inner medullary collecting duct (IMCD) cells were
      removed from these animals and were stimulated with graded doses of vasopressin.
      Cells from cisplatin-treated rats showed an impaired response in cAMP generation
      to vasopressin stimulation as compared to cells from normal animals. To determine
      more precisely the site of impairment, the adenylate cyclase complex of the IMCD
      cells was further studied with forskolin and NaF. Forskolin was used to probe the
      catalytic unit activating adenylate cyclase, and NaF the guanine nucleotide
      regulatory protein (G protein). In response to forskolin, cells from cisplatin
      treated rats and normal rats responded similarly in generating cAMP. However,
      following NaF, the cAMP response was blunted in the cells from the cisplatin
      rats. These results suggested that the catalytic unit was not injured by
      cisplatin (forskolin study) but the G protein was (NaF). In conclusion, the
      present study suggests that the polyuria seen following cisplatin administration
      is associated with an end-organ resistance to vasopressin manifested by reduced
      cAMP generation, secondary in part or whole to a defect at the level of the G
      protein.

PMID- 8302422
TI  - Resolution of membranoproliferative glomerulonephritis complicating
      angiofollicular lymph node hyperplasia (Castleman's disease).
AB  - A novel renal complication was reported in a patient with angiofollicular lymph
      node hyperplasia (Castleman's Disease), who developed acute renal failure due to
      membranoproliferative glomerulonephritis. Renal biopsy showed marked mesangial
      hyperplasia, basement membrane thickening with subendothelial electron-dense
      deposits, interstitial plasma cell infiltration, and glomerular deposition of IgM
      and complement components. A resolution of systemic manifestations and an
      improvement in renal function followed prednisolone and azathioprine therapy.
      Disease relapse, with increasing proteinuria and the development of factor 8
      inhibitor, occurred 3 months later. Sustained remission was achieved with
      prednisolone and cyclophosphamide therapy, which were given for 42 and 12 months,
      respectively. Renal biopsy during remission showed significant resolution of the
      mesangial hyperplasia and disappearance of interstitial plasmacytic infiltration
      as well as subendothelial electron-dense deposits.

PMID- 8302423
TI  - Spontaneous bacterial peritonitis in a hemodialysis patient with systemic lupus
      erythematosus.
AB  - Spontaneous bacterial peritonitis (SBP) is defined as infection of preexisting
      ascites without evidence for any intraabdominal source for secondary infection.
      SBP is now recognized with rising frequency and has mainly been reported in
      patients with alcohol-induced cirrhosis of the liver. We report SBP in a female
      dialysis patient whose ascites was not due to liver disease, but was possibly due
      to lupus erythematosus or represented 'nephrogenic ascites'. The patient had
      severe abdominal pain and a positive rebound phenomenon, fever and an elevated
      peripheral white cell count of 21,000 cells/microliters. Ascitic fluid analysis
      revealed an exudate with a protein concentration of 5.2 g/dl, 13,000 white
      cells/microliters with 94% neutrophils and positive cultures for Streptococcus
      morbillorum. Because of the dramatic clinical features the patient underwent
      laparotomy which did not reveal a source for secondary infection and in
      retrospect was unnecessary. The patient responded well to antibiotic therapy.
      This case report draws attention to SBP as a cause of acute abdomen in patients
      on chronic hemodialysis.

PMID- 8302424
TI  - Anaphylactic reaction to recombinant human erythropoietin.

PMID- 8302425
TI  - Urinary tract infection requiring nephrectomy in a patient with autosomal
      dominant polycystic kidney disease despite ciprofloxacin therapy.

PMID- 8302426
TI  - Prolonged elevation of plasma atrial natriuretic factor does not increase
      erythropoietin levels in patients with chronic renal failure.

PMID- 8302427
TI  - Is the association between crescentic glomerulonephritis and renal cell carcinoma
      coincidental?

PMID- 8302428
TI  - Lipoprotein (a) in chronic renal failure patients undergoing hemodialysis: does
      it have an independent role in the development of further cardiovascular
      complications?

PMID- 8302429
TI  - Disseminated cryptococcosis presenting with a pleural effusion in a kidney
      transplant recipient: early diagnosis by pleural biopsy and successful treatment
      with oral fluconazole.

PMID- 8302430
TI  - Rhabdomyolysis and acute renal failure due to honeybee stings as an uncommon
      cause.

PMID- 8302431
TI  - Relapse of minimal change disease associated with alpha-interferon therapy.

PMID- 8302432
TI  - Volume changes in autosomal dominant polycystic kidneys after the initiation of
      hemodialysis.

PMID- 8302433
TI  - Ultrasonically guided percutaneous ethanol injection to parathyroid autografts
      for recurrent hyperparathyroidism.

PMID- 8302434
TI  - Dysuria as presenting symptom of necrotizing glomerulonephritis.

PMID- 8302435
TI  - Hypomagnesemic hypocalcemia: a brief report.

PMID- 8302436
TI  - Focal segmental glomerulosclerosis associated with pulmonary sarcoidosis.

PMID- 8302437
TI  - ["Heart transplantation program" in Piedmont. Results of a 3-year activity].
AB  - Since 1990 the "Heart Transplant Program" has been instituted in the Piemonte
      Region. Until now the program had regular development according to the number of
      transplantations and the high quality of clinical results. Sixty heart
      transplantations has been performed with a 36 month survival close to 80%. Our
      data demonstrate that after heart transplantation prognosis of end-stage cardiac
      disease is highly improved either for life expectancy and for quality of life.
      Our program includes several aspects of scientific research from physiology to
      clinic, from biochemistry to immunology, from infectivology to pathology, from
      intensive care to surgery. Several very positive multi disciplinary
      investigations have been activated.

PMID- 8302439
TI  - [Non-invasive evaluation of central venous pressure derived from respiratory
      variations in the diameter of the inferior vena cava].
AB  - To evaluate non invasive means of estimating central venous pressure, the
      respiratory motion of the inferior vena cava (IVC) was analysed by
      echocardiography in 65 patients. The caval index was measured in subcostal views
      within 2 cm of the right atrium origin of IVC. Parameters were correlated with
      simultaneous measured central venous pressure (CVP) by catheter positioned in the
      internal jugular vein. Patients were classified in 3 groups: A) 45 patients with
      caval index > or = 20% and normal CVP; B) 6 patients with caval index > 20% and
      elevated value of CVP; C) 14 patients with caval index < 20% elevated value of
      CVP. Group A and B had no sign of cardiac failure, on reverse group C. Caval
      index was inversely related to mean CVP. A caval index > or = 20% indicate normal
      CVP, a caval index < 20% is related to an elevated value of CVP. This method
      appears to be useful for noninvasive estimation of mean CVP.

PMID- 8302438
TI  - [Thallium-201 myocardial perfusion imaging after aortocoronary bypass in patients
      treated with sulodexide or ASA-dipyridamole].
AB  - The aim of this investigation was to compare the preventive effect of sulodexide,
      a glycosaminoglycan drug, tested versus ASA-dipyridamole association, on the
      occlusion of venous aortocoronary bypass. A group A of 23 patients, for a total
      of 22 anastomosis with internal mammary artery and 46 venous bypass, was treated
      with sulodexide 500 USL/day. A group B of 18 patients for a total of 19
      anastomosis with internal mammary artery and 33 venous bypass, was treated with
      ASA-dipyridamole 300 mg + 400 mg/day. Three and 9 months after surgery, all
      patients underwent thallium-201 myocardial perfusion imaging, associated with
      ergometric test. At the first control after 3 months, reversible perfusion defect
      in one or more myocardial segments was observed in 8 patients of group A and 3
      patients of group B (2 A patients and 1 B patient in non revascularized
      myocardial segments); after 9 months, reversible perfusion defects were observed
      in 4 A patients and in 4 B patients. After 3 months, non reversible perfusion
      defect imaging in non infarcted myocardial segments was observed in 2 A patients
      and in 1 B patient; after 9 months, in 1 patient of both groups. This research
      shows higher incidence, at first control after 3 months, of ischemic reversible
      perfusion defects in patients treated with sulodexide, with an evident
      improvement in some patients recontrolled after 9 months. At the last control
      after 9 months, the scintigraphic findings showed similar evidence of perfusion
      defects in both groups treated with sulodexide or ASA-dipyridamole, with
      concordant angiographic findings (78.6%). Our preliminary results are encouraging
      and suggest further widespread studies on sulodexide therapy.

PMID- 8302440
TI  - [The role of the echo-dipyridamole test in the differential diagnosis of chest
      pain].
AB  - We have verified the utility of echo-dipyridamole test in the diagnosis of chest
      pain of unsure origin, especially in patients who cannot be quickly submitted to
      exercise stress test because of permanent abnormalities at basal ECG or because
      of clinical reasons. 17 patients with chest pain, abnormalities at basal ECG not
      evolutive and insignificant for myocardial ischemia, absence of enzymatic curve,
      were admitted to our hospital from September 1988 to January 1990. All these
      patients were submitted before the ninth and fifteenth day of hospitalization to
      the echo-dipyridamole test. Drugs were discontinued 3 days before the test.
      Dipyridamole was administered intravenously in 4 minutes at dosage of 0.56 mg/kg
      during ECG and echocardiographic monitoring. If no ECG or echocardiographic
      changes were observed, a second intravenous bolus of dipyridamole at a dosage of
      0.28 mg/kg in 2 minutes was made. After the end of infusion continuous ECG and
      echocardiographic monitoring was performed for 20 minutes at least. Blood
      pressure was controlled every 3 minutes. Only the major changes in segmental wall
      motion were considered for analysis to minimize possible errors. Moreover a
      second physician not present during the test, revised in following the wall
      motion changes of all the tests. The test was positive in 5 patients (29%)
      (positive group) and negative in 12 (71%) (negative group). The changes in the
      heart rate and blood pressure observed during the test were not significantly
      different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302441
TI  - [Hypotension following maximum physical exercise. Evaluation of hemodynamic and
      humoral mechanisms].
AB  - The period after exercise has received little attention although there are rapid
      and arge changes in the loading conditions of the heart and circulation which may
      precipitate hypotension or arrhythmias. Little is known of the time course of the
      recovery of cardiac output and humoral changes occurring during this periods.
      After a single bout of prolonged muscular exercise, systolic and diastolic blood
      pressure decrease, sometimes for several hours. In a recent controlled study for
      the possible effects of the expecting of the exercise, a reduction in diastolic
      blood pressure was observed particularly in the first 10 min and lasting to 60
      min. The mechanisms of the acute hypotensive effect of upright dynamic exercise
      have not yet been clarified. Little is known of the time course of the recovery
      of cardiac output, humoral and autonomic changes occurring during this period.
      Conflicting data are presented by different authors. The aim of the present study
      was to study the role of the haemodynamic and humoral changes in the
      modifications in blood pressure occurring in the hour of recovery after maximal
      exercise in normal subjects. Nine normal male volunteers (age: 28:34 years) have
      been studied on 2 separate days. Subjects were studied on a non-exercise
      (control) day (the subjects maintained the upright position for 30 min, followed
      by 60 min supine) and an exercise day (maximal upright bicycle exercise followed
      by supine rest for 60 min), in a random order. The following data have been
      recorded before the test and serially during 60 minute supine: systolic and
      diastolic blood pressure, heart rate, haemodynamic changes (by suprasternal
      aortic Doppler), and humoral changes (renin).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302442
TI  - [Slow-release nicardipine in the treatment of arterial hypertension: comparative
      study vs. an ACE inhibitor].
AB  - The anti-hypertensive activity and influence on some forms of stress of slow
      release Nicardipoine and Captopril were compared using a randomized 2:1 protocol.
      Thirty-six patients, mean age 55.9 years, suffering from slight or moderate
      arterial hypertension were treated with either 40 mg of Nicardipine retard twice
      a day (b.i.d.), or Captopril in a dose of 25 mg (b.i.d.) for 8 weeks. A
      significant reduction was observed in arterial pressure, both in orthostatism and
      clinostatism, following both treatments in comparison to the placebo period, but
      the group treated with slow-release Nicardipine showed a greater and
      statistically significant reduction in arterial pressure. No significant change
      in heart rate was reported using either drug. Non-invasive out-patient monitoring
      of arterial pressure, performed using Spacelabs 5300, showed a significant
      reduction in arterial pressure using both drugs and the conservation of the
      normal circadian rhythm of arterial pressure. The pressure response to the cold
      pressor test (CPT), mental arithmetic test (MAS), and to dynamic and isometric
      effort was positive with both drugs, thus revealing a degree of protection
      offered by treatment using these two substances. In overall terms, the two drugs
      were well tolerated.

PMID- 8302443
TI  - [Effect of calciparine in the mid-term treatment of peripheral arteriopathy of
      the lower extremities].
AB  - The authors examine a series of 20 patients suffering from AOCP (?) at Fontaine's
      2nd stage treated with calciparine s.c. in a single daily dose of 12500 IU for
      three months. The parameters of clinical assessment of claudicatio intermittens
      show statistically significant increases of ILR and ILA which were not correlated
      to marked variations of the Windsor index. The extremely positive results in
      terms of the clinical trend of the disease are encouraging with a view to a more
      extensive application of this therapeutic approach in peripheral arterial disease
      of the lower limbs.

PMID- 8302444
TI  - [Pathologic anatomy of the medical-scientific papers].

PMID- 8302445
TI  - [Respiratory mechanics and gas exchange in anesthesia for laparoscopic
      cholecystectomy].
AB  - OBJECTIVE: To evaluate the influence of endoabdominal CO2 insufflation during
      anaesthesia for laparoscopic cholecystectomy on airway pressure, gas exchange and
      their relationships. DESIGN: Perspective; clinical investigation. SETTING:
      Operating room at a central general hospital. PATIENTS: 14 patients (3 males and
      11 females) ASA 1-2, non smokers, without lung disease, scheduled for elective
      laparoscopic cholecystectomy. INTERVENTIONS: During balanced anaesthesia (N2O/O2,
      Fentanyl, Isoflurane), with fixed minute ventilation, endoperitoneal insufflation
      of CO2 held at constant pressure (21 cm H2O). MEASUREMENTS: Serial measurements
      of: Airway pressure, near-static compliance, ETCO2, CO2 minute production, blood
      gas analysis and derived data: P(a-A)O2, P(a-ET)CO2, Vd/Vt. MAIN RESULTS: During
      insufflation peak and pause pressures increased by 6 cm H2O and mean pressure; by
      3 cm H2O; Compliance was reduced by 48%; PaO2 decreased evenly with time (p >
      0.05) irrespective of the airway pressure. PaCO2, PECO2, VCO2 and Vd/Vt after a
      sharp increase stabilized at 30% (mean value) over the baseline. P(a-ET)CO2 and
      Vd/Vt fluctuate in the physiological range except for two short but significant
      changes (p > 0.05) at insufflation and desufflation time. CONCLUSIONS:
      Laparoscopic technique for cholecystectomy, at least in healthy patients,
      produces relevant changes in airway pressures but only minor modifications of gas
      exchange, similar to those seen during general anaesthesia. This technique can be
      safely used for routine operation with standard monitoring equipment.

PMID- 8302446
TI  - [Computerized recording of physiologic parameters monitored during anesthesia].
AB  - STUDY OBJECTIVE: The aim of the study is to describe a multifunctional anesthesia
      record system PC-based, for use in operating room, and to verify the possibility
      of statistical analysis of some of the signals registered. DESIGN: Anesthesia
      records with data entered automatically were performed in 650 patients undergoing
      anesthesia for abdominal or thoracic surgery. A randomized trial in patients
      allocated into two groups was performed too. The first group was ventilated with
      non rebreathing system, the second group was ventilated with circle system.
      SETTING: Inpatient surgery clinic at a medical center. PATIENTS: 24 patients ASA
      I undergoing general anesthesia for laparoscopic cholecystectomy. INTERVENTIONS:
      The first group was ventilated with O2 = 4 1/min-1 and N2O = 6 1/min-1; the
      second group was ventilated with O2 = 350 ml/min-1 and N2O = 250 ml/min-1,
      reducing the N2O flow in order to keep FIO2 = 0.4. MEASUREMENTS: Esophageal
      temperature was registered every 90 sec and automatically copied on a Microsoft
      Excel spread sheet for statistical analysis. RESULTS: The automated anesthesia
      record was easy to use and different information about anesthesia and surgery
      were recorded. The automated analysis of the signals can be performed if no
      artifacts exist. With this method we found a statistical difference in the
      esophageal temperature between the two groups after 45 min of anesthesia.
      CONCLUSIONS: Computerized records capture many more data than handwritten records
      and give the possibility to give a rationale in their customs.

PMID- 8302447
TI  - [Ambulatory pediatric anesthesia. Personal experience].
AB  - The authors critically examine the preoperative management, the various
      anaesthetic techniques, the perioperative undesired effects in eighty six ASA I
      II paediatric patients (age 6 months-11 years) submitted to ambulatorial
      anaesthesia for minor surgery or endoscopy. The importance of the psychological
      approach to patients and parents is enhanced. The preoperative screening included
      physical examination, ECG and simple laboratory tests. Various anaesthetic
      techniques (tracheal intubation and muscle relaxation with mechanical ventilation
      or spontaneous breathing) and many variously combined anaesthetic drugs (propofol
      2 mg/kg, ketamine 1.5 mg/kg, diazepam 0.15 mg/kg, thiopental 3-4 mg/kg, halothane
      1-2 MAC, fentanyl 1 microgram/kg) were employed depending on the quality of the
      surgical procedure and the conditions and the age of the patient. The results
      show that arousal was always rapid and smooth. The residual analgesia was
      sufficient in 74 cases; the other patients received rectal paracetamol 250 mg. No
      major complication was observed and only 6 patients were discharged 1 day later
      on account of vomiting or low Steward score. In conclusion outpatient paediatric
      anaesthesia has no contraindication for ASA I-II patients, shows no major
      complication and is well accepted by the patients and their patients.

PMID- 8302448
TI  - [Brain death: physiopathology and current diagnostic approach].
AB  - The concept of death has undergone many changes in the centuries depending on
      ages and social contexts. However death has always been identified by heart and
      respiratory irreversible arrest. In the last 30 years this concept has been
      suddenly and deeply modified by cardiocirculatory and respiratory support
      techniques. The real boundary between life and death is cerebral activity. When
      this latter causes the subject can be considered dead. In the large majority of
      cases the clinical and this strumental neurological findings are sufficient for
      the diagnosis of brain death. However in many other cases this diagnosis may be
      difficult because of problems in the ascertainment of the complete and
      irreversible lack of cerebral activities. In these cases many an strumental
      techniques (evoked potentials, Doppler and nuclear medicine studies) can help in
      the diagnosis.

PMID- 8302449
TI  - [Reliability of sedation in MRI].
AB  - In our work we have an enumeration of 1527 sedation cases to carry out RM exams
      with non co-operating patients, most of them in pediatric age. During the
      examination the patients were monitored using oximeter and observed by closed
      circuit camera. The meaningless complications head us to think that deep sedation
      is a reliable procedure which allows us to work out RM exams during a day
      hospital regime.

PMID- 8302450
TI  - [Postoperative intravenous analgesia].
AB  - The authors report the results of two clinical studies on postoperative pain
      relief with PCA. In the first clinical study 44 patients, undergoing gynecologic
      surgery, were assigned at random to two groups. The first was treated by PCA
      (infusor Baxter) with morphine i.v. (basal bolus 0.05 mg/kg, loading doses 1 mg
      every 6-15'), the second with 10 mg morphine i.m. at the end of surgery and then
      on demand with a lock-out of 6h at least. In the 2nd clinical study, 40 elder
      patients submitted to orthopedic surgery, were assigned at random to two groups
      treated with PCA (morphine i.v., basal bolus 0.07 mg/kg, bolus PCA 0.007 mg/kg
      lock-out 15') and with continuous infusion (i.c.) (basal bolus 0.07 mg/kg, i.c.
      0.02 mg/kg/h). Our data were analyzed with Student's "t" unpaired test and showed
      lower doses of the drug in the groups PCA (1st study PCA 25.98 mg/48h, i.m. 45.45
      mg/48h, 2nd study PCA 0.155 mg/kg/12h, i.c. 0.311 mg/kg/12h) and lower rate of
      side effects in the same groups. Side effects were well controlled using
      symptomatic drugs. We proposed to our patients, at the end of observation, a
      questionnaire about general conditions, sleep, pain evaluation using a
      descriptive scale and retrospective evaluation. Patients and nurses agree PCA.
      Nursing staff expressed a positive opinion and patients said they benefitted from
      PCA. As reported, PCA appears from our results, valid and safe in postoperative
      pain relief.

PMID- 8302451
TI  - [Evaluation of the effectiveness of NSAIDs in the prevention of postoperative
      pain. Comparison between pre- and postoperative administration of sodium naproxen
      in orthopedic surgery].
AB  - The aim of the study was to assess the efficacy of the preoperative sodium
      Naproxen administration to reduce analgesic requirements in the postoperative
      period. 75 patients (ASA I-II), 50 male and 25 female, aged between 25 and 70
      years and weighed between 50 and 90 kg, undergoing lumbar laminectomy were
      subjected to the same anesthetic technique. Patients were allocated randomly to
      one of three groups. Group I received intravenous sodium naproxen (550 mg)
      immediately after induction of anesthesia. Group II received intravenous sodium
      Naproxen (550 mg) at the end of surgery. Group III received intravenous normal
      saline immediately after induction of anesthesia. Postoperative every patient was
      given by request intramuscular Buprenorphine (0.3 mg) for pain relief (at 6 h
      intervals). Buprenorphine requirements in the group I were significantly lower
      than in either of the other groups (p < 0.01 and p < 0.0001 respectively), while
      significant differences were not observed between group II and III. Moreover the
      54% of patients in the group I did not require analgesic drugs in the
      postoperative period in opposition to the 20% of pts. in the group II and the 12%
      of pts. in the group III (p < 0.05 and p < 0.01 respectively). We conclude that
      NSAIDs when given before tissue damage may prevent nociceptor sensitisation and
      probably reduce hyperexcitability of the spinal cord. Preoperative administration
      of NSAIDs provides better protection against peripheral nerve sensitisation than
      postoperative administration.

PMID- 8302452
TI  - [Use of a new type of permanent caval filter in a case of recurrent pulmonary
      embolism].
AB  - We describe a case of postoperative recurrent pulmonary embolism, treated with a
      percutaneous caval filter ("Double hooks DF 06-Filcard"), that was useful for
      stemming the tide of venous thromboembolism starting from right leg deep venous
      thrombosis. We discuss diagnostic protocols, current indications to caval
      filtration, and the characteristic of an ideal caval filter.

PMID- 8302453
TI  - [Acute carbamazepine poisoning treated with plasmapheresis. Description of a
      clinical case].
AB  - A case of severe Carbamazepine poisoning initially misdiagnosed is reported.
      Treatment consisted in plasmapheresis (3.5 liters exchanged) repeated for 3
      consecutive days, in conjunction with activated charcoal and advanced life
      support. It was obtained a rapid decay in Carbamazepine plasmatic level (with
      rebound phenomenon only after first treatment day) and a contemporary improvement
      in clinical conditions. The patient was discharged without complications after 6
      days stay in ICU. Taking pharmacokinetic characteristics into account, it is
      suggested that plasmapheresis may be useful in this kind of poisoning.

PMID- 8302454
TI  - Low-antigen-content diet in the treatment of patients with IgA nephropathy.
AB  - Since dietary macromolecular antigens can be involved in the pathogenesis of IgA
      nephropathy (IgAN), the effect of a low-antigen-content diet was evaluated in 21
      patients (10 women, 11 men, mean age 27.7 +/- 10 years) with immunohistochemical
      findings of active IgAN. The diet was followed for a 14-24-week period (mean 18.8
      +/- 6); in all cases the effects of the treatment were evaluated by clinical and
      serological parameters, and in 11 patients also by repeat renal biopsy. After
      dietetic therapy a significant reduction of urinary proteins was recorded (P <
      0.001); in particular, heavy proteinuria (> 1 g/day), present in 12 cases during
      the 6 months preceding the treatment, was markedly reduced or disappeared in 11.
      At post-treatment control biopsy mesangial and parietal deposits of
      immunoglobulins, complement C5 fraction and fibrinogen were significantly
      reduced. The improvement of the objective parameters such as heavy proteinuria, a
      strong predictor of a poor prognosis, and of immunohistochemical alterations
      indicate that a low-antigen diet can positively affect patients with IgAN. These
      results could be ascribed to a reduction of nephritogenic food antigen input and
      to a putative functional restoration of the mononuclear phagocytic system.

PMID- 8302455
TI  - Contrasting renal haemodynamic effects of protein in normal subjects and
      glomerulonephritic patients with impaired renal function.
AB  - The effects of a protein load on renal haemodynamics in patients with renal
      failure are controversial. We measured insulin clearance (Cin) and PAH clearance
      (CPAH) by constant infusion technique in six healthy subjects and 13 patients
      with biopsy-confirmed glomerulonephritis and chronic renal failure. The subjects
      were pre-equilibrated on their usual diet and studied before and 2 h after 1 g
      protein/kg as cooked red meat. In healthy subjects this caused a significant
      increase of Cin (from 136 +/- 7.2 (SD) to 148 +/- 7.9 ml/min/1.73 m2) and of CPAH
      (from 547 +/- 142 to 639 +/- 89). In contrast Cin decreased from 72.7 +/- 7.7 to
      60.3 +/- 8.4 in patients with chronic renal failure, whereas CPAH showed no
      significant change (from 275 +/- 67.8 to 278 +/- 72.7). A similar decrease of Cin
      was also seen with acute infusion of amino acids (AA). The change in Cin was not
      related to changes of PRA or concentrations of plasma amino acids. While absolute
      and fractional Na excretion increased in controls, they decreased in patients in
      parallel with the decrease of Cin. The decrease of Cin after infusion of AA was
      amplified by pre-equilibration on low-sodium diet (20 mmol Na/day). The effect of
      meat ingestion on Cin was not obliterated, however, by pretreatment with
      captopril (25 mg b.i.d. for 7 days). In conclusion, in patients with chronic
      renal failure, a paradoxical decrease in Cin is seen both after oral protein and
      after amino-acid infusion.

PMID- 8302456
TI  - Characterization of a non-Goodpasture autoantibody to type IV collagen.
AB  - Goodpasture's syndrome is a very severe and aggressive autoimmune kidney disease.
      The patients' autoantibodies, which are pathogenic, are restricted to the C
      terminal region of the alpha 3-chain of type IV collagen. In this paper we
      characterize an anti-type IV collagen antibody from a patient with a non
      progressive form of glomerulonephritis. ELISA and immunoblotting were used to
      study the specificity of this patient's antibodies. The patient had high titres
      of antibodies restricted to the C-terminal region of the alpha 1-chain of type IV
      collagen. The antibody recognized an epitope hidden in the NC1 molecule which was
      fully exposed after denaturation or reduction. It was an IgG3 antibody composed
      of only lambda light chains, indicating that it has a potential to induce
      inflammatory damage and that it is probably monoclonal. This patient also had MPO
      ANCA which were of IgG1 subclass. Our patient had no disease progression during
      the 5 years of treatment. Even though the anti-alpha 1 (IV) antibodies react with
      the same domain, but of a different chain of type IV collagen compared to the
      Goodpasture's antibodies, they do not induce any severe damage. It is thus
      uncertain if the anti-alpha 1 (IV) antibodies have any pathogenic role; the
      kidney damage might have been caused by the MPO-ANCA. The findings support the
      theory that the anti-alpha 3 (IV) antibody causes disease in Goodpasture's
      syndrome and that antibodies restricted to other subunits of the C-terminal
      region of type IV collagen are less harmful.

PMID- 8302457
TI  - CR1 activity on erythrocytes and renal glomeruli in patients with renal
      disorders.
AB  - Complement receptors for C3b/C4b (CRI) on erythrocytes (ERC1) and renal glomeruli
      (GCR1) were examined in patients with different types of renal disorders. Normal
      ECR1 activity was found on erythrocytes from patients with IgA
      glomerulonephritis, benign nephrosclerosis and other types of renal diseases. In
      patients with systemic lupus erythematosus (SLE) and glomerulonephritis ECR1
      activity was low or absent in 75% of the patients. The GCR1 activity, however,
      was normal except in areas with complement deposits where GCR1 activity was
      abolished. During treatment with corticosteroids and azathioprine of patients
      with SLE the clinical response was followed by increased functional ECR1
      activity. In those patients who did not respond the ECR1 activity was
      persistently low. Three patients with renal transplant all showed increased ECR1
      activity.

PMID- 8302458
TI  - Does erythropoietin cause hormonal changes in haemodialysis patients?
AB  - In 10 female and 10 male haemodialysis patients plasma FSH, LH, testosterone,
      prolactin, and somatotropin (STH) were estimated during erythropoietin (rHuEpo)
      treatment for 6 months. All but one patient responded with an increase in
      haemoglobin. The patients experienced improved sexual function according to the
      answers given in a self-administered questionnaire. Of the 90% who answered
      before the study 22% could not perform sexual activities whether they wanted to
      or not. During and at the end of the study 80 and 60% respectively answered, and
      none had these problems. In contrast, serum values of the sexual hormones (FSH,
      LH, testosterone and prolactin) were not significantly changed during rHuEpo
      therapy, and neither was the basal plasma STH.

PMID- 8302459
TI  - Increased red cell 2,3-diphosphoglycerate levels in haemodialysis patients
      treated with erythropoietin.
AB  - The efficacy of recombinant human erythropoietin (rHuEpo) for the treatment of
      renal anaemia is well established. To assess the effect of rHuEpo treatment on
      physical performance we evaluated physical working capacity, oxygen uptake and
      red cell 2,3-diphosphoglycerate (DPG) values at rest and during and after
      exercise on a bicycle spiroergometer in eight chronically haemodialysed patients.
      Follow-up examination was carried out after a mean of 14 weeks (range 9-19
      weeks), when mean haemoglobin had increased from 7.8 to a stable value of 13.0
      g/dl in response to rHuEpo treatment (P < 0.001). Physical working capacity and
      oxygen uptake at the anaerobic threshold (4 mmol/l blood lactate concentration)
      increased from 68 +/- 12 to 80 +/- 16 watts and 0.95 +/- 0.14 to 1.10 +/- 0.20
      l/min, respectively (P < 0.01). DPG, which determines oxygen affinity to
      haemoglobin in red cells, increased by 13% from 13.7 +/- 1.5 to 15.5 +/- 2.2
      mumol/g Hb (P < 0.05). With maximal exercise mean DPG values significantly
      decreased to a much lower level without rHuEpo treatment than after correction of
      anaemia. Therefore rHuEpo treatment results both in better oxygen transport
      capacity and reduced intraerythrocytic oxygen affinity, which is followed by
      improved oxygen delivery to tissues per unit of haemoglobin. These effects may
      explain the improvement of exercise capacity observed in dialysis patients after
      rHuEpo treatment.

PMID- 8302460
TI  - Adherence of human monocytes to haemodialysis membranes.
AB  - In the present study we evaluated spontaneous and stimulated adherence of human
      monocytes to regenerated cellulose and polyacrylonitrile (AN69) membranes.
      Spontaneous adherence at 60 min was significantly higher for regenerated
      cellulose (28 +/- 2%, P < 0.001) than for AN69 (11 +/- 2) membranes. Stimuli such
      as bacterial lipopolysaccharide, TNF alpha, interleukin-1 and -6 as well as
      platelet-activating factor, but not IL-4, significantly enhanced adherence at 60
      min to AN69 (28 to 30%). In contrast, adherence was not further inducible in the
      presence of regenerated cellulose. Both spontaneous and cytokine/bacterial
      lipopolysaccharide-stimulated adherence were significantly reduced by SDZ-63072,
      a specific platelet-activating factor receptor antagonist. This difference in
      sensitivity of monocyte adherence reflects probably the intrinsic ability of
      regenerated cellulose to provide maximal spontaneous monocyte adhesion. These
      data suggest that PAF may act as an adherence mediator. This is in line with the
      ability of regenerated cellulose to directly stimulate monocytes to synthesize
      platelet-activating factor and with the ability of cytokines and bacterial
      lipopolysaccharide to stimulate its synthesis. Although AN69 has a low adherence
      potential, bacterial lipopolysaccharide or cytokines may blunt the
      biocompatibility of this membrane.

PMID- 8302462
TI  - Calcium mass transfer in CAPD: the role of convective transport.
AB  - One hundred and fifty calcium (Ca) balance studies were performed in 50 patients
      treated with CAPD using dialysate with a 1.75 mmol/l (7 mg/dl) Ca content, in
      order to calculate the peritoneal balance of Ca by measuring the Ca in all the
      effluent for a 24-h period, and looking at the influence of serum ionized Ca and
      the ultrafiltration rate in the calcium balance. Of the 150 balance studies, 77
      were made using four exchanges of dialysate per day and 73 using three exchanges
      per day. The serum ionized Ca was 1.17 +/- 0.09 mmol/l, the ultrafiltration 844
      +/- 723 ml/day and the peritoneal Ca transfer 39 +/- 46 m/day. The net Ca
      abortion with four exchanges was less than that with three exchanges per day.
      There was a strong negative correlation between the peritoneal Ca absorption and
      the ultrafiltration (r = -0.7, P < 0.00001) and with the ionized Ca (r = -0.49, P
      < 0.0001). Thirty-three peritoneal balance studies showed a negative Ca balance
      and in all 33 cases ultrafiltration was greater than 350 ml/day. We conclude that
      the peritoneal balance of Ca depends not only on the serum ionized Ca, but also
      on ultrafiltration. The lesser Ca gain observed with four dialysis exchanges per
      day is due to greater ultrafiltration rates present in this setting.

PMID- 8302461
TI  - Citrate versus heparin anticoagulation in chronic haemodialysis patients.
AB  - Anticoagulation with citrate at a rate of 0.68 mM/min in combination with a
      calcium and magnesium-free dialysate and i.v. supplementation of calcium and
      magnesium at rates of 0.18 mM/min and 0.08 mM/min respectively, was compared with
      low-dose heparin. The heparin dose was a loading dose of 2500 IU and a sustaining
      infusion of 750-1250 IU/h; or a loading dose of 1250 IU and a sustaining infusion
      of 500-750 IU/h until 1 h before the end of the dialysis if the patient was
      taking concomitantly coumarin anticoagulation for a Goretex shunt. Six chronic
      haemodialysis patients changed from heparin to citrate anticoagulation because
      they reported bleeding between dialyses. Heparin, after 2 h dialysis, induced a
      significant 10% prolongation of each patient's whole-blood activated clotting
      time (WBACT) as compared to the predialysis value; while the WBACT at the
      dialyser outlet was less than 3% prolonged as compared to the patient's WBACT.
      However, after 2 h citrate the patient's WBACT was not prolonged but the WBACT at
      the dialyser outlet was 20-100% longer, indicating a better anticoagulation of
      the extracorporeal system without systemic effects. With heparin the shunt
      pressure time (SPT), i.e. the time needed to stop bleeding from the puncture
      sites of the Goretex shunts, was 12 of 28 times 20 min or more. Citrate reduced
      these episodes by 75%. Thus citrate should be considered for chronic
      haemodialysis patients who are at risk of bleeding because of the concomitant use
      of anticoagulants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302463
TI  - Major reduction of CAPD peritonitis after the introduction of the twin-bag
      system.
AB  - In recent years an impressive decrease in the incidence of CAPD-related
      peritonitis was observed in our centre, from 1.4 in the mid-eighties to 0.4 per
      patient year in 1991. In order to analyse which factors were most responsible for
      this decline, the present study was performed. From the start of our CAPD
      programme in 1982 until September 1991, 100 patients were enrolled. For each
      patient, time elapsed from catheter insertion until first peritonitis episode was
      recorded. Outcome was measured as the peritonitis-free interval in days. The
      following variables have been evaluated: age, gender, type of catheter, type of
      system, presence of diabetes mellitus, leakage, break-in period, presence of an
      exit-site infection, and performing surgeon. Data were analysed first by Kaplan
      Meier product-limit estimate of survival (peritonitis-free interval). Thereafter
      Cox proportional hazard analysis was applied to the data, providing a conditional
      probability of peritonitis at each moment during follow-up, given a certain
      combination of risk factors. Our results show that the system, in conjunction
      with the type of catheter, was a decisive factor in the decline of the
      peritonitis rate in our centre. Patients on the twin-bag system (twin-bag group)
      showed a significant increase in the peritonitis-free interval in comparison with
      patients using other systems (non-twin bag group). Among the other variables
      analysed, only diabetes mellitus appeared to be relatively important. Episodes of
      culture negative peritonitis were more frequently observed in the twin-bag group,
      compared to the non-twin bag group. In absolute numbers Staph. non-aureus was the
      micro-organism most effectively reduced.

PMID- 8302464
TI  - An analysis of adequacy of dialysis in a selected population on CAPD for over 3
      years: the influence of urea and creatinine kinetics.
AB  - Adequacy of dialysis is addressed to minimize the negative consequences of
      underdialysis. The results of the NCSD demonstrated that urea kinetic modelling
      (UKM) is a useful tool in the measurement of adequacy of dialysis: Kt/V values of
      1 are considered adequate to prevent complications when daily protein intake is
      appropriate. For CAPD no similar prospective studies exist, and consequently
      there is no information comparable to that for haemodialysis. Preliminary data
      have communicated controversial results about the usefulness of UKM for CAPD
      prescription. On the other hand creatinine kinetics has been proposed as an
      alternative to UKM to define adequacy of dialysis on CAPD. However, these results
      should be considered preliminary because of the small size of the series and the
      short observation period. The objective of this paper is to study the role of
      these two kinetic models in defining adequacy of dialysis in a long-term,
      selected CAPD population. We have studied 56 patients treated for at least 3
      years on CAPD (3-11 years; mean observation period 5 years; 3996 patient-months).
      Urea kinetic model (UKM) (urea weekly (W) Kt/V and NPCR) and creatinine kinetics
      (Efficacy number (EN) and K) were determined annually. According to the present
      data we can conclude that Kt/V is an appropriate tool for defining adequacy in
      patients on CAPD. Values of weekly Kt/V greater than 1.7-1.8, with NPCR more than
      1 g/kg/day, assure an adequate clinical outcome. Conversely, values on the Kt/V
      scale less than 1.7 entail a greater rate of complications. Our data also confirm
      that maintaining a serum albumin > 536-551 mumol/l (3.7-3.8 g/dl) is related to
      lower morbidity and mortality, and should be a major objective for CAPD patients.
      Consequently a relationship between dose of dialysis in terms of urea mass
      balance and protein nutrition can be established. After 5 years on CAPD, when all
      residual renal function is generally lost, Kt/V values in excess of 1.9 are
      difficult to achieve. Based on currently available information, we do agree with
      the interest of performing a prospective study on adequacy of dialysis based on
      the urea kinetic model in CAPD, which definitely defines its role. On the other
      hand, creatinine kinetics did not show sufficient discriminative capacity in
      terms of adequacy of dialysis. EN and Kt of creatinine values in the lower range
      (4.5-6 and less than 45-50 1/week respectively) were not necessarily associated
      with a poorer clinical outcome.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8302465
TI  - Gingival overgrowth among renal transplant recipients and uraemic patients.
AB  - No detailed data exist on an association between combined cyclosporin (CsA) and
      dihydropyridine (DHP) medication and gingival overgrowth among renal patients.
      Thirty-five renal transplant recipients treated with CsA and 28 uraemic patients
      participated in this research. Fourteen of the recipients and 14 of the uraemic
      patients were receiving DHP. The examination included determination of the
      duration of the CsA and DHP treatment protocols, the mean daily oral dose of DHP,
      and periodontal status. Gingival overgrowth was classified into four categories
      according to the clinical changes: score 0 = no gingival overgrowth, score 1 =
      mild gingival overgrowth, score 2 = moderate gingival overgrowth, and score 3 =
      severe gingival overgrowth. The prevalence of clinically obvious gingival
      overgrowth (scores 2 and 3) was 35% in those treated with CsA and DHP, 24% with
      CsA and 21% with DHP. The concomitant administration of CsA and DHP resulted in a
      significantly increased percentage of scores 2 and 3 overgrown gingival units as
      compared with DHP alone (P < 0.05). Gingival overgrowth (scores 1, 2, 3) did not
      correlate with either the daily oral dose of DHP or the duration of DHP
      treatment. Combined treatment with CsA and DHP did not significantly increase the
      prevalence of gingival overgrowth, but it did increase the severity of it among
      susceptible patients.

PMID- 8302466
TI  - Low-dose cyclosporin nephrotoxicity in the rat.
AB  - The nephrotoxicity of cyclosporin (CsA) continues to be a clinical problem that
      detracts from its obvious benefits as an immunosuppressive agent. Animal models
      designed to study the problem have generally relied either on chronic
      administration of high doses of the drug or acute administration of single i.v.
      doses. The present study establishes a model of CsA nephrotoxicity using doses of
      the drug comparable to those used in man administered over a time period
      sufficient for haemodynamic and structural changes to become evident. The
      technique used measures glomerular filtration rate (GFR) and effective renal
      plasma flow (ERPF) by the plasma clearance of chromium EDTA and iodohippuran
      respectively. This has the advantage of allowing sequential measurements in
      individual animals. Significant impairment of GFR was seen in animals treated
      intraperitoneally with doses of CsA as low as 5 mg/kg/day. CsA 7.5 mg/kg/day
      caused a significant reduction in ERPF, and at 10 mg/kg/day and greater
      filtration fraction also declined significantly. Detailed histological
      examination of the kidneys from these animals also revealed significant tubular
      dilatation at 10 mg/kg/day and above. This model of CsA toxicity circumvents many
      of the problems associated with other models. The animals can be studied
      longitudinally and the period of administration has relevance to clinic practice.
      This work provides the basis for further studies which can closely mimic the
      clinical situation using doses similar to those used for human maintenance
      immunosuppression.

PMID- 8302467
TI  - Erythropoietin-induced hypertension without raising haematocrit.

PMID- 8302468
TI  - Goodpasture's syndrome with asymptomatic renal involvement. Disappearance of
      antiglomerular basement membrane antibodies deposits after treatment.

PMID- 8302469
TI  - Tumoral calcinosis in haemodialysis patients without severe hyperparathyroidism.

PMID- 8302470
TI  - Antiphospholipid syndrome and glomerular thrombosis in the absence of overt lupus
      nephritis.

PMID- 8302471
TI  - Renal vascular disease in patients with primary antiphospholipid antibodies.

PMID- 8302472
TI  - Antithrombin III supplementation allowed haemodialysis without heparin after
      kidney transplantation.

PMID- 8302474
TI  - Erythropoietin does not increase whole-blood platelet aggregation in vitro.

PMID- 8302473
TI  - Successful treatment of acute D-lactate encephalopathy by haemodialysis.

PMID- 8302475
TI  - Manual reprocessing of haemodialysers using peracetic acid.

PMID- 8302476
TI  - Sperm body in the urinary sediment.

PMID- 8302477
TI  - Removal of complement factor D by adsorption on polymethylmethacrylate dialysis
      membranes.

PMID- 8302478
TI  - OKT3: a therapeutic alternative in recurrence of focal glomerulosclerosis in the
      transplanted kidney?

PMID- 8302479
TI  - Correction of hyperlipidaemia in a nephrotic patient during an episode of anuria.

PMID- 8302480
TI  - Interaction between alpha-interferon and erythropoietin in antiviral and
      antineoplastic therapy in uraemic patients on haemodialysis.

PMID- 8302481
TI  - Renal abscess in a young woman after delivery.

PMID- 8302482
TI  - Acquired factor VIII autoantibody (AAb) in the course of lipoid nephrosis.

PMID- 8302483
TI  - Update on phosphate binders.

PMID- 8302484
TI  - Essential trace metals: new definitions based on new paradigms.
AB  - This article will concentrate on the nutritional and physiological aspects of
      modern trace metal research. It will try to establish meaningful relations among
      the research activities of the past 50 years, and to summarize the present state
      of knowledge as a basis for future endeavors. The discussion will address the
      gradual emergence during the past decades of three paradigms that can be expected
      to determine the directions of future research.

PMID- 8302485
TI  - Diet and exercise in obese subjects: self-report versus controlled measurements.
AB  - Past decades have witnessed a continuing discussion on the relative role of food
      intake in the pathogenesis of obesity. Some observers argue that overeating is
      paramount; others claim that the obese are metabolically more efficient in energy
      utilization, and thus may not need as much food. There is a considerable amount
      of evidence that big people do need more food than those who are smaller and
      thinner. However, a recent study using advanced techniques has revealed a clear
      discrepancy between self-reported and actual energy intake and self-reported and
      actual physical activity in obese subjects, especially those who had great
      difficulty in losing weight by dietary means.

PMID- 8302486
TI  - Ascorbic acid bioavailability in foods and supplements.
AB  - The bioavailability of ascorbic acid from food has been assumed to be high, but
      little quantitative information has been available to substantiate this
      assumption because of the limited precision and low statistical power of previous
      studies. A recent depletion-repletion study with a more effective experimental
      design has shown clearly that ascorbic acid bioavailability is equivalent in
      ascorbic acid tablets (with and without iron), orange juice, whole orange
      sections, and cooked broccoli. The bioavailability of ascorbic acid in raw
      broccoli was 20% lower, although this difference would probably have little
      nutritional significance in typical mixed diets.

PMID- 8302487
TI  - Nuclear signaling pathways for 1,25-dihydroxyvitamin D3 are controlled by the
      vitamin A metabolite, 9-cis-retinoic acid.

PMID- 8302489
TI  - Interleukin-2 production is altered by copper deficiency.
AB  - Copper is an essential nutrient for optimal function of the immune system;
      deficiency results in impairment of both humoral and cell-mediated components.
      Copper deficiency in rodents results in decreased numbers of CD4+ (helper) and
      total T cells. This defect has been traced to impaired production of interleukin
      2, a cytokine essential for T-cell division and differentiation. Impairment of
      quiescent cell proliferation is reversed by both in vivo and in vitro copper
      supplementation.

PMID- 8302488
TI  - Hypercholesterolemia of copper deficiency is linked to glutathione metabolism and
      regulation of hepatic HMG-CoA reductase.
AB  - Copper deficiency in rats causes hypercholesterolemia and increases in hepatic
      glutathione concentration and HMG-CoA reductase activity. Prevention of the
      increase in hepatic glutathione abolished the other changes.

PMID- 8302490
TI  - Dietary supplements: rationale for regulation.

PMID- 8302491
TI  - Vitamin B6 and immune competence.
AB  - Animal and human studies suggest that vitamin B6 deficiency affects both humoral
      and cell-mediated immune responses. Lymphocyte differentiation and maturation are
      altered by deficiency, delayed-type hypersensitivity responses are reduced, and
      antibody production may be indirectly impaired. Although repletion of the vitamin
      restores these functions, megadoses do not produce benefits beyond those observed
      with moderate supplementation. Additional human studies indicate that vitamin B6
      status may influence tumor growth and disease processes. Deficiency of the
      vitamin has been associated with immunological changes observed in the elderly,
      persons infected with human immunodeficiency virus (HIV), and those with uremia
      or rheumatoid arthritis. Future research efforts should focus on establishing the
      mechanism underlying the effects of vitamin B6 on immunity and should attempt to
      establish safe intake levels that optimize immune response.

PMID- 8302492
TI  - Interactions between nutrition and infection with human immunodeficiency virus.
AB  - Nutritional status is severely compromised in persons infected with the human
      immunodeficiency virus (HIV). One or a combination of several disease-related
      factors can contribute to substantial weight loss and malnutrition, accelerating
      the downhill course of the disease. Efforts to prevent weight loss should include
      early intervention aimed at appetite stimulation, nutritional supplementation
      with high-calorie, high-protein oral supplements, and diagnosis and treatment of
      underlying infections and malabsorption. Although enteral or parenteral feedings
      may be warranted, these forms of nutritional support pose special problems in HIV
      infected persons, and the ultimate benefits of these measures are not yet clear.
      The recent use of pharmacologic agents to stimulate appetite or improve body
      composition shows promise, but more research is needed before these drugs can be
      widely recommended as adjuncts to therapy. In general, unproven remedies should
      be avoided, as their risks may well outweigh their benefits.

PMID- 8302493
TI  - Menkes' disease: perspective and update on a fatal copper disorder.
AB  - Although the causes of the abnormal copper utilization seen in Menkes' disease
      remain unknown, a candidate gene reported by three laboratories has narrowed the
      search for the defective or missing factor. These genetic studies also suggest
      that a copper ATPase may be important in normal copper metabolism.

PMID- 8302494
TI  - Cerebral cortex docosahexaenoic acid is lower in formula-fed than in breast-fed
      infants.
AB  - Docosahexaenoic acid (22:6n-3) is abundant in the brain and retina and may be
      important for optimal nervous system development. Although current infant
      formulas available in the United States do not contain this fatty acid, it is
      found in human milk. In a recent study, the concentration of 22:6n-3 in cerebral
      cortex phospholipids was lower in full-term formula-fed infants than in infants
      who were breast-fed.

PMID- 8302495
TI  - Fish-oil supplementation reduces intestinal hyperproliferation in persons at risk
      for colon cancer.
AB  - Hyperproliferation in the upper compartments of colonic crypts is associated with
      an increased risk for colon cancer. A recent short-term, double-blind, placebo
      controlled study found that fish-oil supplementation (8 g/day) reduced the rate
      of proliferation in the upper crypt cells of patients with a history of colonic
      polyps.

PMID- 8302496
TI  - Mutations in the copper- and zinc-containing superoxide dismutase gene are
      associated with "Lou Gehrig's disease".
AB  - Recent genetic analyses of patients with a familial, chromosome 21-linked form of
      amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrig's disease,
      suggest that mutations in the cytosolic copper/zinc superoxide dismutase (SOD1)
      gene may be involved in development of the disease. Although no functional
      disturbance of SOD1 activity has yet been identified, altered free radical
      protection may contribute to the destruction of motor neurons. The role of
      antioxidant status needs to be investigated as a possible preventive and
      therapeutic intervention for ALS.

PMID- 8302497
TI  - New recommendations for the diagnosis and treatment of plasma lipid
      abnormalities.
AB  - Elevated total blood cholesterol levels (at or above 240 mg/dL) due to increased
      low density lipoprotein (LDL) cholesterol values (at or above 160 mg/dL) have
      been associated with an increased risk of coronary heart disease (CHD). It has
      been shown in controlled prospective studies that when LDL cholesterol is lowered
      with diet or diet and drug treatment, subsequent risk of CHD morbidity and, in
      some cases, mortality can be reduced. New guidelines have recently been released
      by the Adult Treatment Panel (ATP II) of the National Cholesterol Education
      Program (NCEP). Risk factors for CHD in addition to elevated LDL cholesterol now
      include: 1) male 45 years or older; 2) female 55 or older, or with premature
      menopause and not on estrogen replacement; 3) high density lipoprotein (HDL)
      cholesterol less than 35 mg/dL; 4) hypertension; 5) cigarette smoking; 6)
      diabetes mellitus; and 7) a family history of premature CHD. After screening with
      total cholesterol and HDL cholesterol measurements, patients with total
      cholesterol values at or above 200 mg/dL, HDL cholesterol below 35 mg/dL, and/or
      CHD should have a fasting cholesterol, triglyceride, and HDL cholesterol
      measurement. Candidates for diet therapy are those with LDL cholesterol values at
      or above 1) 160 mg/dL; 2) 130 mg/dL in the presence of two or more CHD risk
      factors; or 3) 100 mg/dL in the presence of CHD. Candidates for drug therapy
      after diet treatment are those with LDL cholesterol values at or above 1) 190
      mg/dL; 2) 160 mg/dL in the presence of two or more CHD risk factors; or 3) 130
      mg/dL in the presence of CHD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302498
TI  - An audit and international comparison of asthma management in the emergency
      department.
AB  - AIMS: 1. To perform an audit of asthma management in the Christchurch Hospital
      emergency department during the period March 1987 to August 1988. 2. To compare
      management of asthma in Christchurch with other centres in New Zealand and the
      United Kingdom. 3. To compare markers of asthma severity on admission with other
      centres. METHODS: Details of all attendances by adults to the Christchurch
      Hospital emergency department with acute asthma during the above period were
      recorded on specially designed asthma treatment sheets. This data was compared
      with similar studies performed in Wellington (NZ) and Southampton and Leicester
      (UK). RESULTS: 759 cases were analysed. Most subjects were in the 15-25 year age
      group. 47% were taking inhaled corticosteroids at presentation. History taking
      was satisfactory according to guidelines operative at that time. Peak flow rate
      measurement at presentation was performed in 79% of cases, and in 67% of cases
      following treatment. Nebulised bronchodilators were given in 88% of cases and
      parenteral steroids given in 22%. 46% of cases were discharged home and of these
      28% received a course of oral prednisone. All management decisions, except the
      decision to give oral steroids on discharge, showed a relationship to objective
      indices of asthma severity. CONCLUSION: Comparison with other centres shows that
      the treatment of acute asthma in Christchurch was of a similar standard. Severity
      of asthma on presentation, as measured by peak flow and pulse rates showed no
      difference between Christchurch and Southampton.

PMID- 8302499
TI  - Huntington's disease and predictive testing.

PMID- 8302500
TI  - A survey of wasp sting injuries in urban Auckland from December to April in
      1991/2 and 1992/3.
AB  - AIM: To determine the numbers and the seasonal variations in patients seeking
      medical consultation for wasp sting injuries in urban Auckland. METHOD: A monthly
      record of the number of people seeking treatment for wasp stings was kept by 50
      general practitioners from 18 medical centres and accident and emergency
      departments from three hospitals in urban Auckland. RESULTS: From December to
      April, 47 people in 1991/2 and 49 in 1992/3 received treatment for wasp sting
      injuries from the family practitioners surveyed. In addition, 27 people and 35
      people received treatment at the three accident and emergency clinics over the
      same time period in 1991/2 and 1992/3 respectively. Paper wasps were found to be
      responsible for the majority of the sting injuries reported. CONCLUSION: Our data
      indicates that wasp stings have a significant impact on the health of the
      Auckland population and indicates the urgent need for more detailed studies in
      other parts of New Zealand.

PMID- 8302501
TI  - Case finding in the elderly: a postal questionnaire.
AB  - AIMS: To evaluate a postal questionnaire designed to identify elderly persons in
      need of geriatric evaluation and intervention in the community. METHODS: A sample
      of elderly persons, over 75 years, was randomly selected from the age-sex
      register of four general practices in the Auckland area. All respondents filled
      out postal questionnaires and a blinded assessment was made in their own homes
      using validated geriatric assessment tools (the reference test). Objective
      evaluations were compared to self report questionnaire results and sensitivity,
      specificity, positive and negative predictive values were calculated. RESULTS:
      Sixty-four persons aged 75-93 were evaluated. Thirty-nine subjects (61%) answered
      the questionnaire in a way which indicated they had one or more unmet needs.
      Reference test evaluations showed that 23 persons (36%) had problems in one or
      more areas. Sensitivity for the questionnaire was 0.78 (18/23 correctly
      identified) and specificity was 0.49. Positive and negative predictive values
      were 46% and 80% respectively. CONCLUSIONS: A postal questionnaire may be a
      useful adjunct to health surveillance of the elderly in general practice in New
      Zealand.

PMID- 8302502
TI  - A survey of urban and rural participants in the Otago-Southland pilot breast
      cancer screening programme.
AB  - AIMS: By surveying participants in a pilot breast cancer screening programme, to
      measure satisfaction with the screening service, to provide feedback for
      programme staff, to obtain an indication of future participation, and to collect
      information about costs to women. METHODS: A self administered questionnaire was
      posted to representative samples of urban and rural women (total 474) who had
      participated in the Otago-Southland pilot breast cancer screening programme in
      its first year of operation. RESULTS: There was a 93% response rate to the
      survey, after one reminder letter. Although some demographic characteristics of
      urban and rural women differed, their opinions about the screening programme were
      similar. Satisfaction with the service is extremely high, with 94% of respondents
      planning to participate again in two years. CONCLUSIONS: The Otago-Southland
      pilot programme provides a service which is regarded as satisfactory by the great
      majority of participants.

PMID- 8302504
TI  - The crime of failing to record instructions.

PMID- 8302503
TI  - Exercise classes in rest homes: effect on physical function.
AB  - AIM: To determine if regular exercise classes, planned and supervised by a
      physiotherapist, improved physical function in a sample of frail
      institutionalised elderly. METHOD: Weekly one hour and twice weekly 10 minute
      exercise classes were given by a physiotherapist, to a group of 34 residents who
      consented from randomly selected rest homes. The study took place over a period
      of one year. At entry, 4, 9 and 12 months the physical function was compared with
      the matched control group who received regular rest home activities, without
      physiotherapy input. The study used a sit stand test to measure change in
      physical function. This was indicated by recording (a) the time taken and (b) the
      hand assistance required to stand up. RESULTS: Compared with the control group,
      the study group showed statistically significant improvement (p < 0.05) in
      physical function as measured by sit stand time. The sit stand hand assistance
      test was found to be too insensitive to measure improvement or to differentiate
      between the two groups. The programme was enjoyable and had no health
      complications. CONCLUSION: Regular exercise classes planned and supervised by a
      physiotherapist are safe and improve the physical functioning and daily activity
      levels of the frail, institutionalised elderly. They are a cost effective use of
      the physiotherapist's limited time.

PMID- 8302505
TI  - Hookworms presenting in New Zealand.

PMID- 8302506
TI  - Hormone replacement therapy.

PMID- 8302507
TI  - Streptococcal sore throat.

PMID- 8302508
TI  - An unusual case of lead poisoning.

PMID- 8302509
TI  - The demise of public health in New Zealand?

PMID- 8302510
TI  - Seller beware.

PMID- 8302511
TI  - Phantom tooth pain: differential diagnosis and treatment.

PMID- 8302512
TI  - Phantom tooth diagnosis and an anamnestic focus on headache.
AB  - The cause of atypical odontalgia has been related to many factors, including
      psychological ones. Animal experiments indicate that tooth pulp extirpation
      provokes a deafferentation, which may or may not induce pain, depending on
      unknown factors. The research described here showed that human tooth avulsion
      induces atypical odontalgia when it is carried out in migraine and cluster
      headache sufferers. Conversely, no sensation is reported by personally and
      familiarly headache-exempt subjects who underwent the same type of tooth
      extraction.

PMID- 8302513
TI  - Orofacial pain management: clinical and medicolegal problems.

PMID- 8302514
TI  - Determining factors of the phantom tooth.
AB  - Painful and painless phantom tooth phenomena can often be understood only by
      means of extensive inquiry. The presence of the phenomena appears to be
      influenced by demographic factors such as age. Other factors include an advance
      of the circadian phase position from an ergotropic state of the central nervous
      system and personality dispositions such as introversion.

PMID- 8302515
TI  - Atypical odontalgia. Its aetiology and prognosis.
AB  - Atypical odontalgia is a chronic pain disorder in which persistent pain develops
      in clinically normal teeth. Its possible aetiology and long-term prognosis are
      discussed. Suggested management regimes are reviewed.

PMID- 8302516
TI  - A philosophy for the profession of dentistry.

PMID- 8302517
TI  - Season's greetings! Come what may.

PMID- 8302518
TI  - A valuable lesson.

PMID- 8302519
TI  - From Task Force on Issues Related to AIDS. I don't need those anymore!

PMID- 8302520
TI  - Public health issues also essential to health care reform. Nursing in the
      community.

PMID- 8302521
TI  - Daylight, diet, and age-related cataract.
AB  - Blindness due to cataract continues to take a heavy toll on economic, social, and
      personal resources. Research into factors that may cause or prevent cataracts is
      of the highest priority. In this paper, the epidemiological evidence is
      summarized on the role of sunlight exposure and antioxidants for cataract. To
      date, there are consistent findings linking ultraviolet B (UV-B) radiation to
      cataract, particularly cortical and posterior subcapsular opacities. Antioxidants
      are likely to exert a protective effect against oxidative stress in the lens, but
      the current epidemiologic data present less coherent support for this hypothesis.
      Difficulties in summarizing these data include different methods for assessing
      antioxidant status, widely varying populations, and different research designs.
      Nevertheless, most studies have found some measure of antioxidant status to be
      associated with some type of cataract. Future research directions are described.

PMID- 8302522
TI  - Phase separation inhibitors and lens transparency.
AB  - A phase separation inhibitor, WR77913 [S-3(amino-2-hydroxypropyl)
      phosphorothioate], was tested for its effects on lens opacification in the
      radiation (RAD), selenite (SEL), galactose (GAL), streptozotocin (STZ), and Royal
      College of Surgeons (RCS) models for cataract. A single i.p. injection of
      WR77913, approximately 15 min before induction of cataract formation by RAD, SEL,
      STZ delayed or inhibited opacification. Repeated administration was necessary to
      delay or inhibit opacification in the GAL or RCS models for cataracts. The
      results suggest that phase separation inhibitors such as WR77913 have the
      potential to delay or inhibit lens opacification resulting from a variety of
      physiological or biochemical mechanisms.

PMID- 8302523
TI  - Considerations in the subjective assessment of cataract.
AB  - The subjective classification of lens opacities is a fundamental component in
      both the clinical evaluation of the individual patient and in large-scale
      clinical trials. This procedure has been improved substantially by the
      implementation of standardized photographic systems depicting various levels of
      nuclear opacity and color, cortical, and posterior-subcapsular cataract.
      Comparison can also be made with recently developed objective measurements of
      opacity and color. Further improvements in reliability and sensitivity to change
      can be achieved by modifying traditional integer scaling systems by interpolating
      between photographic standards.

PMID- 8302524
TI  - Quantitating cataract and nuclear brunescence, the Harvard and LOCS systems.
AB  - Subjective and objective systems are used to quantify cataract at The Center for
      Clinical Cataract Research. We have described each system and its use, presented
      data on reproducibility and validity, and for objective systems, demonstrated the
      correlation to the subjective grade of the cataract as defined by the Lens
      Opacities Classification Systems, Versions II and III (LOCS II and III). The
      subjective systems are used to classify nuclear color, nuclear opalescence,
      cortical cataract, and posterior subcapsular cataract. Reported kappa scores for
      LOCS II range from 0.85 to 1.0. Intraclass correlation coefficients for LOCS III
      (r1) range from 0.67 to 0.94. The computerized objective system are: (1) fast
      spectral scanning colorimetry (FSSC) for assessment of nuclear color (r1 = 0.96
      to 0.98); (2) nuclear mean density (NMD) for assessment of nuclear opalescence
      (r1 = 0.97); and (3) percent area opacity (anterior = a; posterior = p) (OPAC-a
      and OPAC-p) for assessment of cortical and posterior subcapsular cataract (r1 =
      0.92 to 0.96).

PMID- 8302525
TI  - Evaluating visual function in cataract.
AB  - This paper reviews recent research on the evaluation of visual function in
      cataract. Visual impairment in cataract is principally caused by increased
      intraocular forward light scatter. It is assumed that visual acuity (VA)
      measurements assess the impact of narrow angle light scatter. This also makes the
      measurement of high spatial frequency contrast sensitivity (CS) unnecessary.
      However, VA measurements alone are an inadequate assessment of visual impairment
      in some patients with cataract. In addition, it is suggested that a measurement
      of wide-angle light scatter is required. This can be evaluated directly using the
      van den Berg Straylightmeter, or indirectly using low spatial frequency CS or
      disability glare (DG) tests. The following are discussed: (1) the relative
      usefulness of these tests; (2) how they can be incorporated into the decision as
      to when to extract a cataract; and (3) the importance of considering binocular
      visual function.

PMID- 8302526
TI  - Assessing vision behind cataract--a review of methods.
AB  - The clinician involved in cataract assessment is often faced with a deterioration
      in visual performance which may or may not be totally attributable to the
      cataract. Neural changes may occur concurrently and contribute toward the reduced
      performance. This paper reviews the methods which attempt to discriminate between
      changes due to cataract development and changes produced by neural degeneration.
      New techniques have been developed with more emphasis on quantitative rather than
      qualitative assessment. These techniques are discussed critically with particular
      reference to their ability to distinguish between the contributions of optical
      and neural change. This has particular application in predicting the visual
      outcome after cataract surgery.

PMID- 8302527
TI  - Contrast detection in noise: a new method for assessing the visual function in
      cataract.
AB  - The detectability of a signal decreases in the presence of externally added
      visual noise. A linear relation exists between the energy of a signal at
      threshold and the spectral density of the added visual noise. This relation,
      represented by contrast detection in noise function, allows a given loss in
      contrast sensitivity (CS) to be attributed to an increase in the internal
      intrinsic noise and/or a decrease in the detection efficiency of the observer.
      Intrinsic noise gives a measure of the random background noise within the visual
      system, whereas detection efficiency is a measure of how effectively the observer
      utilizes the available stimulus information. Recent work shows that neural
      dysfunction produces a decrease in the detection efficiency, whereas optical
      deficits produce a change in the intrinsic noise only. We investigated whether
      the CS loss in cataract can be attributed to either a change in intrinsic noise,
      in detection efficiency, or both. Contrast detection in noise functions was
      measured for 10 uniocular cataract patients. Comparison between the two eyes
      showed no significant difference in detection efficiency, although the intrinsic
      noise increased significantly in the cataractous eye. The data suggest that
      detection efficiency may provide a measure of neural visual function behind a
      cataract and, conversely, that intrinsic noise provides a measure of the visual
      effect of the cataract itself. We discuss the implications of intrinsic noise as
      a measure of cataract for both clinical assessment and research.

PMID- 8302528
TI  - Evaluation of lens opacities classification system III applied at the slitlamp.
AB  - The Lens Opacities Classification Systems (LOCS III) was developed and
      standardized using photograding. The purpose of this study was to assess the
      validity of LOCS III at the slitlamp and to compare slitlamp with photograding.
      To do so, two independent observers graded cataract at the slitlamp and in
      photographs from two sets of patients; the first set consisted of 205 eyes (193
      acceptable photographs) and the second set of 51 eyes (51 photographs). The 95%
      tolerance limits (TL) for grading at the slitlamp ranged from 0.9 to 1.8 for the
      first set and 0.6 to 1.2 for the second (intraclass correlation coefficients 0.79
      to 0.91 vs. 0.70 to 0.97, respectively). Specifically, there was a significant
      decrease in 95% TL for cortical and nuclear color. For the first set of
      photograding, the 95% TL were 0.3 to 0.6 between the two observers and 0.6 to 0.8
      for the same observer at two different sessions. Similar results were found for
      photograding the second set. The 95% TL for comparing slitlamp and photograding
      were generally > 1.0. The results suggest that (1) LOCS III at the slitlamp has
      95% TL only slightly worse than those for LOCS III photogradings; (2) LOCS III
      slitlamp grading for cortical and nuclear color improves with practice; and (3)
      the slitlamp and photographic gradings cannot be used interchangeably.

PMID- 8302529
TI  - Classification and protein distribution in a series of intracapsular cataracts.
AB  - The crystallin profiles of the cortices and nuclei of intracapsular cataractous
      lenses were studied by high pressure liquid chromatography (HPLC), polyacrylamide
      gel electrophoresis (PAGE), and dot blotting. The complete personal and medical
      history of 381 patients and the Cooperative Cataract Research Group (CCRG)
      classification of each were obtained. Few statistically significant associations
      between patient personal history and cataract types were found. Protein profiles
      of selected cataracts which had specifically located opacities (i.e., nuclear
      only, cortical only, etc.) were studied in detail. Sodium dodecyl sulphate-PAGE
      revealed few differences in lens-soluble proteins between cataractous and normal
      cortices or nuclei. By HPLC, the proteins of cataractous cortices and their
      nuclei differed very little from age-matched controls. The cortical proteins of
      nuclear cataracts appeared normal. However, two major alterations of proteins
      were observed in the nuclei of dense nuclear cataracts. Increased high molecular
      weight protein and increased components with molecular weights < 20,000 Da were
      found in cataractous nuclei as compared with normal age-matched control lens
      nuclei. Dot blot (immunological) analyses identified the crystallins of normal
      lenses that eluted from the HPLC column more efficiently than those of
      cataractous lenses. Cortical protein HPLC samples had the most specificity.
      Nuclear protein HPLC samples of older normal and cataractous lenses had little if
      any alpha crystallin specificity in the void volume peak. A relation between the
      presence of opacities and changes in molecular weight distribution of crystallins
      was found in the opaque nuclei but not in the opaque cortices.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8302530
TI  - Lovastatin and the human lens; results of a two year study. The MSDRL Study
      Group.
AB  - Lovastatin has been associated with development of subcapsular cataract in dogs
      given high doses. To test the cataractogenic potential of lovastatin in humans,
      192 patients were divided into 2 groups, A (N = 94) and B (N = 98), 1 taking 40
      mg/day of lovastatin and 1 taking placebo. Both groups were enrolled for 2 years
      in this double-blind, randomized study and were followed with eye examinations
      including assessment of visual function, Lens Opacities Classification System II
      (LOCS II) cataract and nuclear color classification, and computerized lens image
      analysis. There were no statistically significant differences in visual function
      between the two groups. Similarly, cataract progression, assessed by LOCS II
      measurement and by computerized measurements of cataract, showed no important
      differences between the treatment groups. These data show no cataractogenic
      effect of lovastatin in humans.

PMID- 8302531
TI  - A noninvasive video-based method for measuring lens transmission properties of
      the human eye.
AB  - The Lens Absorption Monitor (LAM) is an automated video-based system for
      obtaining rapid objective noninvasive measurements of the spectral transmission
      properties of the human lens. The technique is based on intensity measurements of
      the 4th Purkinje image for different wavelengths, and incorporates several
      features that overcome some of the difficulties associated with previous studies
      using this approach. LAM transmission measures for the visible spectrum can be
      obtained in approximately 2 s, and in most instances can be obtained without
      having to dilate the subject's eye. This paper describes the technique and
      presents our initial findings for 40 normal observers between the ages of 24 and
      77 years. Results of the LAM technique show that it is able to measure the
      wavelength-dependent properties of the lens accurately and to identify age
      related changes in "yellowing" of the lens. Test-retest reliability of the LAM is
      better than for psychophysical estimates of ocular media transmission. LAM and
      psychophysical measures in the same subjects were found to be correlated,
      although LAM measures produced consistently lower values of lens density than the
      psychophysical determinations. There was only moderate agreement between LAM and
      psychophysical measures of lens density. Possible explanations for these
      differences are discussed. Future research will determine whether this technique
      is able to detect and quantify early cataract development.

PMID- 8302532
TI  - Objective line spread function measurements, Snellen acuity, and LOCS II
      classification in patients with cataract.
AB  - We tested an instrument to measure the line spread function (LSF) of the eye in
      order to assess objectively retinal image degradation due to cataract. Optical
      aberrations from 62 eyes with early to moderate cataract were assessed by
      measuring the extent of blurring of a best-focused fine line image (LSF)
      projected onto a subject's retina. The instrument consisted of a slitlamp
      equipped with a Hruby lens to project the line and a computer-coupled CCD camera
      to record and measure the blurred image. We hypothesized that the width of the
      blurred line image (called WSCAT) due to light scattering in the cataractous lens
      would be affected most by nuclear and subcapsular cataracts. The WSCAT results
      were compared to the data from two other tests: (1) Snellen acuity and (2) LOCS
      II cataract classification. Grouping eyes by Snellen acuity we found that WSCAT
      from the group with 6/4.5 (20/15) or 6/6 (20/20) acuity was distinguishable from
      the group with 6/9 (20/30) or worse acuity (95% confidence interval). Data also
      were analyzed using a regression model which corrects for the intraclass
      correlation between the two eyes of an individual. Results show a significant
      association between WSCAT and minimum angular resolution (MAR) derived from
      Snellen visual acuity (regression coefficient of 5.45, p = 0.008). WSCAT also is
      correlated with both LOCS II nuclear opalescence (NO) and posterior subcapsular
      (P) categories with regression coefficients of 3.03 (p = 0.004) and 2.07 (p =
      0.054), respectively. Results from measurement of LSF indicate the potential for
      this instrument to assess retinal image degradation associated with nuclear and
      posterior subcapsular cataract objectively.

PMID- 8302533
TI  - Light scatter in the normal young, elderly, and cataractous eye demonstrates
      little wavelength dependency.
AB  - The purpose of the study was to investigate whether light scatter in normal
      young, elderly, and cataractous eyes exhibits significant wavelength dependency.
      Straylight was quantified by calculating light scatter factors (LSF's) based upon
      the reduction in contrast sensitivity produced by a glare source. The angle of
      the glare source relative to fixation was varied (3.25 to 26 degrees), as was its
      wavelength (460 to 660 nm). LSF's increased as a function of age an especially in
      the presence of media opacities. However, the relation between LSF and glare
      angle remained approximately the same for each group. Our results suggest that
      wavelength dependency in normal young, elderly, or cataractous eyes is rather
      unimportant relative to other factors.

PMID- 8302534
TI  - Measurement of glare susceptibility using low-contrast letter charts.
AB  - The Committee on Ophthalmic Procedures Assessment of the American Academy of
      Ophthalmology suggested either contrast sensitivity or low-contrast visual acuity
      (VA) measured before and after adding a glare source as a test for assessing
      overall visual disability from immature cataracts. We have developed a test that
      follows the Committee's three principles of design, and we report that the effect
      of glare on VA is considerably greater for recognizing low-contrast letters than
      for recognizing high-contrast letters. The effect of glare on VA increases
      progressively as letter contrast is reduced from 96% through 50%, 25%, 11%, and
      4%. The 25% chart (and possibly the 11% chart) gives the most suitable
      sensitivity for eyes with immature cataracts. Neither age-related brunescence and
      aging itself nor even the presence of a distinct opacity necessarily produces
      high sensitivity to glare. The test is sensitive enough to detect an ageing
      effect even before the age of 45 to 55 years and to reveal large intersubject
      differences among normally sighted 19- to 25-year-old subjects.

PMID- 8302535
TI  - Controlling unwanted sources of threshold change in disability glare studies: a
      prototype apparatus and procedure.
AB  - One of the main purposes of cataract surgery is to reduce the debilitating
      effects of light scatter by the lens. An important effect of this intraocular
      forward scatter is to produce a veiling retinal illuminance from a glare source.
      The retinal contrast of the stimulus is thus reduced, and a quantifiable
      "disability glare" effect may be measured. A complication is introduced by the
      fact that intraocular scatter arises from other sources in addition to the lens.
      All present tests of glare disability fail to eliminate or control for these
      factors, nor do they control for the light adaptation effect of the glare source.
      The effects of lens removal may not be predicted accurately by such tests, and
      patients may report little improvement in visual function after surgery. The goal
      of this research is to provide the background for developing a method of
      measuring disability glare due only to light scatter in the lens. Thirty-seven
      patients with mild to moderate cortical cataracts served as subjects. A
      disability glare effect (DG) was measured with a Maxwellian-view system that
      eliminates or controls scatter from the iris, sclera, and retina, and which
      controls for light-adaptation effects from the glare source. DG with this method
      showed a significant correlation with objective measures of lens light back
      scatter. Suggestions were made for improvements in the apparatus and procedures
      for future clinical studies.

PMID- 8302536
TI  - Visual performance and objectively measured grades of cataract. A correlation of
      methods designed for use in longitudinal trials.
AB  - Objective quantification of cataract and subjective assessment of visual
      performance are essential features of anticataract or cataractogenic drug trials.
      The constrains of a longitudinal trial require a compromise in contrast
      sensitivity measurement between sensitivity and speed. Such a system has been
      developed for use in longitudinal anticataract trials. An objective cataract
      assessment system has also been developed for these trials. Visual performance
      parameters and objectively measured grades of cataract using these systems were
      correlated in a group of patients with early lens opacities. Overall the
      correlation was poor in all three morphological types of cataract. Possible
      reasons for this and implications for future anticataract trials are discussed.

PMID- 8302537
TI  - Cataract: a critical problem in the developing world.
AB  - Cataract blindness is a major public health problem worldwide. Unlike other
      leading causes of blindness, cataract can be treated effectively with surgery.
      Demographic, social, and economic factors are important determinants of surgical
      treatment of this disorder in the developing world, resulting in the accumulation
      of very large numbers of unoperated cases. Because of many factors, the problem
      is really out of hand. In this paper, we try to raise awareness among
      optometrists of this major challenge. At the same time, because many individuals
      do not achieve good vision after surgery and because in most developing countries
      only one eye is operated upon, we emphasize the use of improved prognostic
      techniques to make the surgical outcome more predictable, avoiding nonproductive
      surgery and resultant disappointment on the part of all concerned. We feel
      optometry can play important roles in diagnosis, visual correction, and
      management of these patients, hopefully in cooperation with ophthalmic surgeons.

PMID- 8302538
TI  - Hemorrhagic macular cysts.

PMID- 8302539
TI  - Extraocular muscle sarcoid.

PMID- 8302540
TI  - National outcomes of cataract extraction. Retinal detachment and endophthalmitis
      after outpatient cataract surgery. Cataract Patient Outcomes Research Team.
AB  - BACKGROUND: A near-total shift to cataract extraction on an outpatient basis
      occurred as a result of an administrative ruling by the Health Care Financing
      Administration. No national study has been conducted to assess the possible
      effects of that decision on clinical outcomes of surgery. The authors compared
      the rates of retinal detachment (RD) repair and hospitalization for
      endophthalmitis after extracapsular cataract extraction (ECCE) (including
      phacoemulsification) in 1986 and 1987 with those following inpatient cataract
      extraction in 1984. METHODS: Using the 5% random sample of Medicare
      beneficiaries, we analyzed the claims of all individuals 66 years of age or older
      who underwent ECCE by nuclear expression or phacoemulsification in 1986 and 1987.
      A total of 57,103 patients were identified and followed to the end of 1988.
      Cumulative probability of RD repair and hospitalization for endophthalmitis was
      calculated by standard lifetable methods. These findings were compared with the
      cumulative probability of the same complications in a cohort of 330,000 patients
      who underwent cataract extraction on an inpatient basis in 1984. RESULTS: In the
      1986-to-1987 cohort, the cumulative probability of RD within 3 years after
      cataract surgery was 0.81% and the cumulative probability of endophthalmitis
      within 1 year was 0.08%. The rate of RD is similar to that which we previously
      reported for 330,000 patients who underwent inpatient surgery in 1984, but the
      rate of endophthalmitis is significantly lower in the 1986-to-1987 outpatient
      cohort (0.08% versus 0.12%; z = 2.42; P = 0.01). CONCLUSIONS: The shift to
      outpatient cataract surgery was accompanied by no significant increase in the
      probability of RD repair and possibly a significant decrease in the rate of
      hospitalization for endophthalmitis.

PMID- 8302541
TI  - Clear lensectomy and implantation of low-power posterior chamber intraocular lens
      for the correction of high myopia.
AB  - BACKGROUND: Although a variety of surgical procedures to treat high myopia have
      been studied, no consensus exists on the optimum procedure. Clear lensectomy with
      implantation of a posterior chamber intraocular lens has been regarded as risky,
      due to the higher incidence of retinal detachment in highly myopic eyes. METHODS:
      The authors performed surgery and evaluation over 1 year in 52 eyes in which
      prophylactic retinal treatment, clear lensectomy, and posterior chamber
      intraocular lens implantation were used to treat high myopia of 12 diopters (D)
      or greater. RESULTS: Before lens extraction, 31 eyes underwent argon laser
      photocoagulation. Over the 1-year period, three additional eyes were treated, and
      six eyes that had been treated preoperatively received additional treatment. No
      cystoid macular edema, retinal detachment, or persistent corneal edema was
      observed in this series. At 1 year, 88.5% of the group achieved corrected visual
      acuity of 20/40 or better, compared with 75% preoperatively. Uncorrected visual
      acuity of 20/100 or better was achieved by 84.6% of the group. The mean
      postoperative spherical equivalent was -0.86 +/- 0.84 D. CONCLUSION: The
      refractive objectives were achieved. Complications reported previously with clear
      lensectomy were not experienced in this group. The low incidence of complications
      can be attributed to the short follow-up and probably in part to the prophylactic
      retinal treatment, combined with the phacoemulsification procedure for lens
      extraction. Longer follow-up is needed to fully assess the complications.
      Properly randomized prospective clinical trials will be able to fully assess the
      benefits and risks of prophylactic retinal treatment and clear lens extraction
      with posterior intraocular lens implantation. This series can help in evaluating
      this surgical procedure.

PMID- 8302542
TI  - Cataract formation and cataract extraction after penetrating keratoplasty.
AB  - PURPOSE: This retrospective study was done to identify risk factors for cataract
      formation and cataract extraction after penetrating keratoplasty to determine
      whether a combined procedure (simultaneous cataract extraction with keratoplasty)
      or penetrating keratoplasty alone should be performed. METHODS: Variables from
      342 phakic eyes having undergone penetrating keratoplasties were studied with
      univariate and multivariate analyses, including diagnosis, race, sex, age,
      preoperative lens opacities, preoperative vision, and length of follow-up.
      RESULTS: For cataract formation, age was the only independent risk factor found
      by multivariate analysis (P = 0.0001). For cataract extraction after penetrating
      keratoplasty, independent risk factors included age, sex, diagnosis, and
      preoperative lens opacities (P < or = 0.03). For example, the probability of a 65
      year-old patient with Fuchs dystrophy requiring a cataract extraction within 5
      years of keratoplasty is 81%. CONCLUSION: The likelihood of cataract formation
      and cataract extraction subsequent to penetrating keratoplasty increases greatly
      after 50 years of age, regardless of the diagnosis leading to the need for
      keratoplasty. The need for cataract extraction also is increased for female
      patients, for patients with Fuchs dystrophy, and for those with early
      preoperative lens opacity.

PMID- 8302543
TI  - Macular dystrophy associated with mutations at codon 172 in the human retinal
      degeneration slow gene.
AB  - BACKGROUND: Recently, mutations in the retinal degeneration slow (rds) gene which
      codes for peripherin-rds have been implicated as a cause of autosomal dominant
      retinitis pigmentosa. Because this gene is expressed in both rods and cones,
      mutations in the rds gene might be expected to cause degeneration affecting
      either the scotopic or photopic systems. Mutations at codon 172 of the rds gene
      have been identified in three families with autosomal dominantly inherited,
      progressive macular dystrophy. METHODS: Affected individuals underwent ophthalmic
      examination, scotopic perimetry, dark adaptometry, measurement of color-contrast
      sensitivity, and electroretinography to characterize the photoreceptor
      dysfunction. RESULTS: In all but one affected member, symptoms of progressive
      central visual loss developed in the third or fourth decade of life accompanied
      by central scotoma and well-demarcated atrophy of the retinal pigment epithelium
      and choriocapillaris of the macula. In general, cone and rod thresholds were
      elevated, and color-contrast sensitivity was absent in the central visual field.
      Peripherally, the scotopic sensitivities were normal, as was the recovery from
      bleach. Cone electroretinograms were diminished in amplitude, and delayed in all
      affected adults except one. Rod electroretinograms were normal or near normal in
      amplitude, and had normal implicit times. Affected asymptomatic children had
      macular changes, abnormal color-contrast sensitivity, and reduced pattern and
      cone electroretinograms. CONCLUSION: These results indicate that mutations in the
      rds gene can be expressed as a macular dystrophy, with evidence of primary cone
      dysfunction and preservation of peripheral rod function.

PMID- 8302544
TI  - Corneal graft survival and visual outcome. A multicenter Study. Corneal
      Transplant Follow-up Study Collaborators.
AB  - PURPOSE: The Corneal Transplant Follow-up Study has followed 2385 corneal
      transplants performed in the United Kingdom and the Republic of Ireland for up to
      450 days to quantify factors influencing corneal graft survival and visual
      outcome 3 and 12 months postoperatively. METHODS: Multifactorial analyses of
      grafts registered by United Kingdom Transplant Support Service from July 1987 to
      June 1990 were used. Corrected visual acuity of functioning grafts was assessed
      at 3 and 12 months. RESULTS: Of 2385 corneal transplants followed, 214 failures
      were observed: graft survival was 95% at 3 months and 89% at 1 year. Similar
      factors affected outcome at each time. Decreased risk of failure was associated
      with surgeons reporting most grafts, and increased risk was associated with
      regrafts, patients younger than 10 years of age, nonvisual reasons for grafting,
      endothelial failure, and deep vascularization. Visual outcome was worse in older
      patients and was associated with cosmetic reasons for grafting, superficial
      vascularization preoperatively, and secondary endothelial failure. Visual acuity
      was better when the other eye had been grafted previously, or when the diagnosis
      was keratoconus or stromal dystrophy. CONCLUSIONS: Primary endothelial failure
      was associated with high failure rates but good visual results when functioning.
      Most other factors had similar effects on both outcome measures. Improved outcome
      under highest-reporting surgeons was slight, and indicated possible differences
      in postoperative care.

PMID- 8302545
TI  - Systemic cyclosporine in high-risk keratoplasty. Short- versus long-term therapy.
AB  - BACKGROUND: In high-risk keratoplasty, the failure rate from rejection is high,
      especially in the early postoperative period. If rejection could be prevented
      during this period, then ultimately a degree of immunologic privilege may be re
      established, resulting in long-term graft survival. Cyclosporine (CSA) given
      systemically prevents graft rejection, but because of the potential side effects
      and cost, the duration of treatment is an important factor. The author examines
      the effectiveness of short- and long-term CSA regimens in preventing irreversible
      graft rejection. METHODS: Forty-three patients with high-risk corneas
      (vascularization in 3 or 4 quadrants and > 16 stromal vessels) received corneal
      grafts and systemic CSA. Fourteen patients received the drug for 12 months and 29
      for a shorter period of 4 to 6 months. A similar high-risk group of 37 patients
      received no systemic medication. RESULTS: In the control group, 23 grafts (62.2%)
      irreversibly rejected, compared with 9 (31.0%) and 1 (7.1%) in the short- and
      long-term CSA groups, respectively. The grafts of patients receiving CSA had a
      significantly better survival rate (P = 0.0005) than those in the control group.
      If time of CSA treatment also was considered, significance increased (P =
      0.00008). CONCLUSIONS: Systemic CSA significantly reduces failure from
      irreversible rejection in high-risk keratoplasty, but for maximal effect, a 12
      month period of treatment is necessary.

PMID- 8302546
TI  - A piggyback contact lens for the correction of irregular astigmatism in
      keratoconus.
AB  - PURPOSE: Although the combination of a hard contact lens "piggybacked" on a soft
      lens base for the correction of severe astigmatism in keratoconus has existed for
      two decades, little is known about its effect on the corneal epithelium and
      endothelium. This study involves two parts: the measure of oxygen pressure in
      rabbits, and the long-term effects on patients with keratoconus wearing these
      hybrid lenses. METHODS: A polarographic sensor was used to measure the oxygen
      pressure on rabbit corneas under two types of piggyback lenses: oxygen-permeable
      hard lenses on high water-content soft lenses, and polymethylmethacrylate (PMMA)
      lenses on low water-content soft lenses. In the clinical evaluation, 11 patients
      with keratoconus (8 men, 3 women; 25.1 +/- 4.9 years of age) who could not wear
      hard contact lenses due to constant pain or inadequate lens fitting were given
      oxygen-permeable piggyback contact lenses and were observed for at least 9
      months. RESULTS: In the animal study, the oxygen pressure under piggybacked
      oxygen-permeable hard contact lenses was 95 +/- 14 mmHg after 5 minutes wear, but
      it was only 34 +/- 14 mmHg when PMMA and low water-content lenses were used. Ten
      of 11 patients were successfully treated using this technique, whereas one
      patient had persistent contact lens loss, requiring penetrating keratoplasty.
      Specular microscopic observation of the corneal epithelium and endothelium did
      not show any changes during the follow-up period. CONCLUSIONS: These results
      suggest the efficacy and safety of the piggyback combination of oxygen-permeable
      hard and soft contact lenses for the correction of astigmatism in patients with
      keratoconus.

PMID- 8302547
TI  - Epithelial and corneal thickness measurements by high-frequency ultrasound
      digital signal processing.
AB  - PURPOSE: The authors determine the mean central corneal and epithelial thickness
      in a group of normal human subjects using a new high-frequency ultrasound
      technique, incorporating digital signal processing. METHOD: Both eyes of ten
      volunteers (age range, 23-44 years) were scanned through a normal saline
      standoff. Digitized ultrasonic echo data were mathematically transformed to
      produce a plot, the I-scan, which optimally localizes acoustic interfaces to
      provide improved measurement precision. System precision was determined by
      analysis of variance of repeated measures. Central epithelial thickness was
      obtained by averaging multiple measurements. Central corneal thickness was
      determined by fitting measurements of apparent corneal thickness in consecutive
      parallel B-scans to a mathematically modeled cornea. A speed of sound of 1640
      m/second was used. RESULTS: Epithelial pachymetric precision using A-scan and I
      scan was 4.8 and 2.0 microns (standard deviation), respectively. The mean
      epithelial thicknesses for the right and left eyes were 50.7 +/- 3.7 microns and
      50.3 +/- 3.4 microns, respectively. The mean corneal thicknesses in the right and
      left eyes were 514.6 +/- 38.4 microns and 516.2 +/- 37.8 microns, respectively.
      The root mean-square differences in epithelial and corneal thickness between the
      left and right eyes of each subject were 1.3 and 7.7 microns, respectively
      (neither was statistically significant). CONCLUSION: This system provides a
      pachymetric precision superior to current optical and ultrasound methods.
      Epithelial and corneal pachymetry is obtained noninvasively by a method that is
      not limited to optically clear media.

PMID- 8302548
TI  - Screening for corneal topographic abnormalities before refractive surgery.
AB  - PURPOSE: The purpose of this prospective study is to evaluate the corneal
      topography of patients who sought an opinion regarding refractive surgery for the
      correction of myopia. METHODS: Both eyes of 53 patients were evaluated with a
      topographic modeling system. Forty-two patients wore contact lenses (84 eyes: 36
      rigid contact lenses and 48 soft contact lenses). Ten patients (20 eyes) wore
      glasses alone and one patient (2 eyes) wore neither glasses nor contact lenses
      for correction of myopia. RESULTS: Thirty-five (33%) of 106 eyes were found to
      have abnormal corneal topography. Of the 42 patients (84 eyes) who wore contact
      lenses, 32 eyes (38%) had irregular astigmatism, loss of radial symmetry, or
      absence of the normal progressive flattening from the center to the periphery of
      the cornea, consistent with contact lens-induced corneal warpage. Alterations
      were more frequent and severe in rigid contact lens wearers. Three patients
      (5.7%) received a diagnosis of definite keratoconus, a higher incidence than has
      been reported in the general population. Topographic abnormalities in most, if
      not all, of the eyes would not have been detected by visual inspection of the
      photokeratoscopic images alone. CONCLUSIONS: Appropriate preoperative detection
      and management of corneal topographic abnormalities are essential steps in every
      refractive surgical procedure. The overall efficacy and safety of procedures such
      as radial keratotomy and photorefractive keratectomy likely will be improved once
      the unpredictable variables of contact lens-induced warpage and occult ectatic
      disease are eliminated by topographic screening before surgery. Patients with
      keratoconus may be over-represented in the refractive surgery population due to
      self-selection.

PMID- 8302549
TI  - Complications of myopic photorefractive keratectomy with the excimer laser.
AB  - BACKGROUND: Although many thousands of myopic eyes have been operated on by
      excimer laser photorefractive keratectomy (PRK), the safety of this procedure is
      still a concern. METHODS: The results and complications of PRK have been studied
      for up to 2 years in a prospective trial including 193 eyes in 146 patients. In
      addition, specific complications of PRK are described that occurred in patients
      outside the prospective study. RESULTS: Two eyes (1.2%) lost two lines of best
      spectacle-corrected visual acuity 1 year after surgery, but at 2 years one of
      these eyes had regained baseline visual acuity. At 1 year, 12 eyes (7.1%) had
      lost more than two lines of visual acuity under glare conditions. Significant
      complications such as manifest scarring, overcorrection, undercorrection, and
      continued regression are dependent on attempted refraction. Eccentric ablations
      with resultant induced astigmatism are rare and the incidence is dependent on the
      experience of the surgeon. Progressive hyperopia did not occur. CONCLUSION:
      Except in corrections greater than 6 diopters, complications after PRK are rare.
      Assuming an appropriate patient selection, PRK may be considered a relatively
      safe procedure compared with other refractive procedures.

PMID- 8302550
TI  - Detection of cellular adhesion molecules in inflamed human corneas.
AB  - PURPOSE: The expression of cellular adhesion molecules in 31 penetrating
      keratoplasty specimens from a broad range of corneal inflammatory diseases was
      studied using monoclonal antibodies and an immunoperoxidase technique. METHODS:
      Corneas were divided into noninflamed, mild to moderately inflamed, and severely
      inflamed groups based on histologic findings. The panel of adhesion molecules
      studied included HLA-ABC, HLA-DR, CD3, LFA-1, MAC-1, ICAM-1, PECAM-1, VCAM-1, and
      E-selectin-1. RESULTS: The adhesion molecules ICAM-1, HLA-DR, PECAM-1, CD3, VCAM
      1, LFA-1, and MAC-1 were selectively expressed in areas of corneal inflammation.
      In general, HLA-DR and intercellular adhesion molecule ICAM-1 were co-expressed
      in similar regions. PECAM-1 was restricted to zones of marked inflammation and
      vascularization. E-selectin-1 was detected only in the stroma of a graft melt in
      a patient with active ocular cicatricial pemphigoid, and may reflect a primary
      regulatory dysfunction in this disorder. The ICAM-1 ligand was, in general, more
      diffusely distributed than its receptor LFA-1, a beta-2 integrin found on
      leukocyte cell membranes. The localization of the integrin MAC-1, present on
      macrophages, neutrophils, and some lymphocytes, did not always parallel the
      staining pattern of ICAM-1, suggesting promiscuity in its binding to other
      ligands besides ICAM-1. CONCLUSIONS: Adhesion molecules are detected readily at
      sites of corneal inflammation and may play a critical role in facilitating the
      recruitment of immune regulatory cells to these areas. Future efforts to block or
      modulate the expression of intercellular adhesion molecules may provide new
      therapeutic options in the treatment of corneal inflammatory diseases.

PMID- 8302551
TI  - Sliding conjunctival flap for the treatment of primary pterygium.
AB  - BACKGROUND: The major problems after pterygium removal are recurrence and
      complications of the therapy. The authors investigated a simple surgical
      treatment without adjunctive therapy for primary pterygium. METHODS: Patients
      eligible to be included in the study were identified from a pterygium treatment
      log. They represent consecutive cases over a 6 1/2-year period, all of whom had
      been treated by one surgeon using a superior, sliding, conjunctival flap to cover
      the pterygium defect. An attempt was made to obtain follow-up of at least 1 year
      for each patient. RESULTS: Two hundred fifty-eight eyes in 236 patients were
      included in the study. Two hundred twenty-two eyes (86%) were able to be followed
      by either record review or re-examination. Seven pterygia (3.2%) recurred, all
      identified by record review, with no recurrences identified by re-examination.
      Recurrences were more likely after early postoperative flap retraction (5 of 7
      recurrences) and recurrence occurred at a mean interval of 4.3 months (range, 1.5
      11 months) after surgery. Symptomatically, the patients were comfortable, and the
      cosmetic result was good. CONCLUSION: This study indicates that this simple
      surgical procedure for the treatment of primary pterygium should be evaluated
      further by controlled clinical trials.

PMID- 8302552
TI  - Histopathologic features of the floppy eyelid syndrome. Involvement of tarsal
      elastin.
AB  - PURPOSE: Patients with the floppy eyelid syndrome have chronic papillary
      conjunctivitis with easily everted upper eyelids and a soft, pliant upper tarsus.
      The purpose of this study is to describe the clinical features and the
      histopathologic correlate in a group of patients with floppy eyelid syndrome.
      METHODS: The authors examined eight patients with floppy eyelid syndrome, four of
      whom underwent surgical management with horizontal eyelid shortening. Eyelid
      tissue from these patients was examined using light microscopy, electron
      microscopy, and immunohistochemistry and compared with controls with unrelated
      eyelid or orbital disorders. RESULTS: Clinical findings included obesity or eye
      rubbing, lash ptosis, and, less commonly, blepharoptosis. Two patients had
      documented sleep apnea with abnormal sleep electroencephalogram. Light microscopy
      of the surgical specimens showed chronic conjunctival inflammation, papillary
      conjunctivitis, and meibomian gland abnormalities, including granuloma formation.
      Verhoeff's modified elastin stain demonstrated a marked decrease in the amount of
      elastin fibers in tarsus from patients with floppy eyelid syndrome compared with
      controls. Immunohistochemical staining for elastin also showed a marked decrease
      of tarsal elastin in floppy eyelid patients compared with controls. In contrast,
      immunohistochemical stains showed that the distribution of collagen types I and
      III was similar between patients with floppy eyelid syndrome and controls.
      Electron microscopy demonstrated that tarsal collagen was comparable in patients
      and controls, and that there was a reduced amount of tarsal elastin in floppy
      eyelid syndrome compared with controls. CONCLUSIONS: These findings demonstrate
      that tarsal elastin is decreased in the floppy eyelid syndrome, which may
      contribute to the laxity of the tarsus in this disorder.

PMID- 8302553
TI  - Absorption of fluorescein given under the upper lid.
AB  - BACKGROUND: The need for a more efficacious approach to administer topical ocular
      medications prompted the authors to consider applying conventional eye drops
      under the upper lid rather than beneath the lower lid. Preliminary observations
      on patients with glaucoma using a beta-blocker beneath the upper lid suggested a
      drop in intraocular pressure into the normal range in some previously refractory
      patients being treated with the same medications. To test this clinical
      observation, the authors observed if there were any physiologic differences in
      topical fluorescein absorption into the anterior chamber when given beneath the
      upper lid versus the lower lid. METHODS: A 5-microliters drop of fluorescein
      solution was placed under the upper-lid fornix of one eye and under the lower-lid
      fornix of the other eye in human volunteers, and absorption into the anterior
      chamber was measured at hourly intervals, for a total of 3 hours. RESULTS:
      Hotelling T2 multivariate analysis for all 3 hours demonstrates that upper-lid
      administration of fluorescein results in significantly higher absorption of
      fluorescein into the anterior chamber than does lower-lid administration (P =
      0.0088; for hours 2 and 3, the statistical differences is even more dramatic: P <
      0.0044). CONCLUSION: Using conventional eye drops beneath the upper lid, the
      authors observed increased absorption of fluorescein into the anterior chamber
      when compared with lower-lid administration. Profuse tearing, especially by
      younger subjects, significantly and rapidly diminished anterior chamber
      absorption of fluorescein. It is reasonable to consider further clinical studies
      to test this new approach to drug delivery.

PMID- 8302554
TI  - Intraoperative adjustable suture surgery for bilateral superior oblique palsy.
AB  - BACKGROUND: The modified Harada-Ito procedure has been reported to be an
      effective treatment for correction of cyclotorsion in bilateral superior oblique
      palsy. However, there are no reports regarding its use in intraoperative
      adjustable suture surgery. METHODS: The authors performed a retrospective study
      of 12 patients with traumatic bilateral superior oblique palsy who were
      classified as having either symmetric or asymmetric palsy according to the
      symmetry of the alternate hyperdeviation on side gazes. Cyclotorsion and vertical
      and horizontal deviation in the nine diagnostic positions were measured
      preoperatively and postoperatively. RESULTS: Of the 12 patients, 6 were
      determined to have symmetric palsy and 6 asymmetric palsy. Intraoperative
      adjustable suture surgery with the modified Harada-Ito procedure was performed
      bilaterally in the six patients with symmetric palsy and unilaterally in those
      with asymmetric palsy. The median measured value of extorsion in the primary
      position was reduced from 14.5 degrees to 2.5 degrees in patients with symmetric
      palsy and from 9.5 degrees to 2.0 degrees in those with asymmetric palsy. In
      downgaze, some degree of residual extorsion remained, and there was no
      significant change in esodeviation after surgery. In five patients with symmetric
      palsy and in all of those with asymmetric palsy, normal single binocular vision
      in the primary position but did not that in downgaze was restored after surgery.
      CONCLUSION: Intraoperative adjustable suture surgery is an effective treatment in
      correcting torsion, but may not be as effective for esodeviation in downgaze.

PMID- 8302555
TI  - New directions for the Ophthalmic Knowledge Assessment Program (OKAP)
      examination.
AB  - BACKGROUND: The Ophthalmic Knowledge Assessment Program (OKAP) Task Force of the
      American Academy of Ophthalmology has reviewed the present OKAP examination and
      addressed the goals of this resident-in-training examination. Simultaneously, the
      American Board of Ophthalmology has been assessing its Written Qualifying
      Examination (WQE) as a certifying tool. METHOD: The history of the OKAP
      examination is chronicled along with a discussion of the goals of this
      examination as a stimulus for resident education. CONCLUSION: The new OKAP
      examination is structured specifically for residents-in-training and is now
      administered separately from the WQE. The OKAP examination is moving in the
      direction of a criterion referenced examination based on a defined content
      outline. Twelve subtest areas are tested. Future goals are to improve subtest
      reliability and increase feedback to residents and program directors.

PMID- 8302556
TI  - The Eye Care Technology Forum. Impacting eye care cost and effectiveness.

PMID- 8302557
TI  - Ab- and ad- vs en- and ex-duction.

PMID- 8302558
TI  - Scleral buckling for retinopathy of prematurity.
AB  - PURPOSE: This study was undertaken to determine the anatomic effectiveness of
      scleral buckling on eyes with stages 4A, 4B, and 5 retinopathy of prematurity.
      METHODS: Seventy eyes of 44 infants had scleral buckling performed by one surgeon
      and were followed for at least 6 months. All except one child had previous
      bilateral peripheral ablation (cryo/laser). RESULTS: Twelve (70%) of 17 stage 4A
      eyes, 29 (67%) of 43 stage 4B eyes, and 4 (40%) of 10 stage 5 eyes had complete
      retinal reattachment or dry folds attached at their last follow-up visit. All
      eyes referred as stage 5 retinopathy of prematurity that reattached had a
      rhegmatogenous component. CONCLUSION: Scleral buckling appears to play a role in
      reducing progression from stage 4 to stage 5 retinopathy of prematurity.

PMID- 8302559
TI  - The pattern visual-evoked potential in former preterm infants with retinopathy of
      prematurity.
AB  - PURPOSE: Flash and pattern visual-evoked potentials (VEPs) were recorded in 89
      former preterm infants (< or = 1500 g birth weight), in whom retinopathy of
      prematurity (ROP) developed that spontaneously regressed without macular
      detachment (stages 2-4a). METHODS: Linear and stepwise regression analyses were
      performed to determine the correlations between transient pattern-reversal P1 VEP
      latency (n = 154 eyes) at a mean of 7.2 years (median, 6.9 years) postnatal age
      using a check size nominally equivalent to 20/100 (30 minutes) and the following
      nine parameters: three immaturity parameters (gestational age at birth, birth
      weight, and ROP zone at 1 month postnatal age); one postnatal insults parameter
      (worst ROP stage); two structural outcome parameters (macular ectopia and vessel
      traction); one functional outcome parameter (visual acuity); and two
      methodological parameters (postnatal age at VEP testing and VEP amplitude).
      RESULTS: Linear regression analyses, with P1 VEP latency as a dependent variable,
      identified the worst ROP stage (r = +0.42; P < 0.0001), macular ectopia (r =
      +0.42; P < 0.0001), visual acuity (r = -0.40; P < 0.0001), and vessel traction (r
      = +0.35; P < 0.0001) as significant correlates. Stepwise regression analysis
      demonstrated that worst ROP stage and macular ectopia accounted for 18% and 4% of
      the cumulative variance, respectively. CONCLUSIONS: P1 VEP latency correlates
      with postnatal insults, structural outcome, and functional outcome parameters in
      former preterms in whom ROP developed that spontaneously regressed without
      macular detachment. A permanent arrest in the development of the macula and/or
      prolonged traction on the incompletely developed macula may alter VEPs.

PMID- 8302560
TI  - Implications of health system reform for eye departments and ophthalmic
      education: the need for a new perspective.

PMID- 8302561
TI  - Retinal detachment with severe proliferative vitreoretinopathy in Terson
      syndrome.
AB  - BACKGROUND: In several reports, early vitrectomy has been proposed for eyes with
      vitreous hemorrhage due to Terson syndrome as a means to hasten visual recovery.
      But the development of nuclear sclerosis and the neurologic problems arising from
      this disease encourage surgeons to wait for spontaneous resorption, especially
      with young patients. Although the formation of epiretinal membranes has been
      described, to the authors' knowledge retinal detachment with proliferative
      vitreoretinopathy in Terson syndrome never has been observed. METHODS: The
      authors report five eyes from four patients with Terson syndrome due to
      spontaneous aneurysm rupture, in whom retinal detachment with proliferative
      vitreoretinopathy developed. RESULTS: The early onset and the severe clinical
      course of proliferative vitreoretinopathy in these eyes showed parallels to
      traumatic proliferative vitreoretinopathy. The retina in all eyes could be
      reattached. CONCLUSION: The authors point out the necessity for accurate and
      close follow-up and early, extensive surgical treatment in Terson syndrome,
      especially in patients with a reduced general state of health.

PMID- 8302562
TI  - Pathology of hereditary retinal degeneration associated with
      hypobetalipoproteinemia.
AB  - BACKGROUND: The clinical features and previously unreported ocular pathology in a
      case of heterozygous hypobetalipoproteinemia (HBL) associated with a pigment
      epitheliopathy are documented. Night blindness developed in a white woman with
      familial heterozygous HBL (cholesterol and low-density lipoprotein levels < 5% of
      normal) at 51 years of age. Ophthalmoscopy showed bilateral symmetric
      depigmentation at the posterior pole with pigment clumping and pavingstone
      configuration in the periphery. By the time the patient died, at 75 years of age,
      vision had deteriorated to hand motions. METHODS: One eye was removed 2 hours
      postmortem for light and electron microscopic study. RESULTS: The photoreceptors
      were absent, and the outer nuclear layer was replaced by glial cells throughout
      most of the retina, but there was some focal photoreceptor preservation in
      isolated regions. The outstanding feature was a massive deposition of basal
      linear deposit which was calcified in segments and which contained macrophages
      and the processes of glial cells: trilaminar bodies and melanin granules were
      identified in the macrophages. The remaining retinal pigment epithelial cells
      contained melanin but very little lipofuscin: intraretinal migration was minimal.
      CONCLUSIONS: The authors postulate that the pigment epitheliopathy associated
      with HBL is an abiotrophy in which photoreceptor discs are unable to regenerate
      due to locally disordered metabolism resulting from or acting in concert with the
      pigment epitheliopathy.

PMID- 8302563
TI  - A masked prospective evaluation of outcome parameters for cytomegalovirus-related
      retinal detachment surgery in patients with acquired immune deficiency syndrome.
AB  - PURPOSE: The management of cytomegalovirus (CMV)-related rhegmatogenous retinal
      detachments in patients with acquired immune deficiency syndrome (AIDS) has been
      the subject of recent attention and controversy because of the high degree of
      variability in visual outcome, as well as significant differences in the reported
      incidence of profound postoperative optic atrophy. This study was designed to
      evaluate the various parameters affecting postoperative visual outcome, and to
      quantitate the degree of postoperative optic disc pallor. METHODS: The results of
      65 consecutive surgeries for CMV-related retinal detachments in 51 patients with
      AIDS were prospectively studied. Postoperative vision, survival, optic disc
      pallor, and retinitis extent were analyzed. Serial photographs of optic discs
      underwent masked evaluation. RESULTS: Mean postoperative survival was 30 weeks
      (range, 2-146 weeks). Mean best postoperative visual acuity was 20/66 (range,
      20/20-2/200) and mean final postoperative visual acuity was 20/100 (range, 20/25
      no light perception). Analysis of visual outcome for eyes with no macular or
      papillo-macular retinitis showed a best postoperative visual acuity of 20/60
      (range, 20/25-2/200) and mean final postoperative visual acuity of 20/80 (range,
      20/25-no light perception). Postoperative vision was not affected by the presence
      of a preoperative macular detachment, with both groups (macula on or off
      detachments), achieving a best postoperative visual acuity of 20/60 in the
      absence of macular retinitis. Mild postoperative optic disc pallor was observed
      in 30% of surgical eyes at the final postoperative visit, and moderate pallor was
      noted in 13%. The mean degree of optic disc pallor was not different from the
      degree of optic disc pallor seen in fellow, nonsurgical eyes with CMV retinitis
      (surgical versus fellow nonsurgical eyes, 29% +/- 23% versus 26% +/- 30%; P =
      0.64). CONCLUSION: In this largest reported series of reattachment surgery for
      CMV-related retinal detachments, patients are experiencing increased
      postoperative survival, good vision, and relative optic nerve health.

PMID- 8302564
TI  - A prospective natural history study and kinetic ultrasound evaluation of
      idiopathic macular holes.
AB  - BACKGROUND: The role of vitreoretinal traction in the macular region as a
      causative factor for the development of idiopathic macular holes is widely
      accepted. The purpose of this study is to provide a prospective evaluation of
      patients with idiopathic macular holes to determine the risk of hole formation in
      the fellow eye. METHODS: The authors performed a prospective study of 50 patients
      with unilateral idiopathic macular holes combining complete ocular examination,
      including slit-lamp biomicroscopy, with kinetic B-scan ultrasound evaluation of
      the status of the vitreoretinal interface. Natural history data were obtained by
      follow-up examinations performed at 3-month intervals throughout the course of
      the study. RESULTS: During a median follow-up of 33 months, a full-thickness
      macular hole developed in 1 (2%) of 46 normal fellow eyes. Full-thickness holes
      also developed in three (75%) of the four eyes that had premacular hole changes
      (stages 1A and 1B) in the fellow eye on initial examination. All macular holes in
      fellow eyes occurred within 24 months of entry into the study. Kinetic ultrasound
      evaluation determined that fellow eyes with separation of the posterior hyaloid
      membrane in the foveal region were protected from future macular hole
      development. Those patients with attachment of the posterior hyaloid membrane in
      both eyes were at highest risk of holes forming in the fellow eye. Patients with
      posterior hyaloid membrane separation in the macular hole eye only, with an
      attached vitreous in the fellow eye, were at intermediate risk. CONCLUSION: The
      authors suggest that fellow eyes in patients with unilateral idiopathic macular
      holes have a relatively favorable natural history and that kinetic ultrasound
      examination may help determine which of these fellow eyes is at highest risk for
      full-thickness macular holes developing.

PMID- 8302565
TI  - Vitrectomy for diabetic macular heterotopia.
AB  - PURPOSE: The authors performed 15 vitrectomies for diabetic macular heterotopia,
      and then compared visual prognoses and postoperative complications with those of
      88 macular detachments to determine the role of, and indications for, vitrectomy
      for diabetic macular heterotopia. METHODS: Fifteen patients with diabetic macular
      heterotopia and 88 with traction macular detachment, in which the vitreous
      cavities were sufficiently clear for posterior poles to be observed, underwent
      vitrectomies. Preoperative and postoperative visual acuity and postoperative
      complications were assessed and documented retrospectively. RESULTS: There was no
      statistically significant difference between the two groups in terms of eyes
      showing improvement in visual acuity postoperatively. However, a final
      postoperative visual acuity better than 20/20 was documented in 93% of patients
      with macular heterotopia and 48% of patients with macular detachment (P < 0.002),
      whereas 47% of the former and 10% of the latter had visual acuities better than
      20/40 (P < 0.001). Postoperative neovascular glaucoma and retinal detachment
      developed in 10% and 13%, respectively, of patients with macular detachments.
      None of the patients with macular heterotopia experienced these complications.
      CONCLUSION: Based on the above results, the authors conclude that diabetic
      macular heterotopia is a very good indication for early vitrectomy.

PMID- 8302566
TI  - The relation of socioeconomic factors to the incidence of proliferative diabetic
      retinopathy and loss of vision.
AB  - PURPOSE: To investigate the relations between socioeconomic factors and the
      incidence of proliferative retinopathy and loss of vision. METHODS: A population
      based sample of younger-onset persons with diabetes 25 years of age or older (n =
      334) and older-onset persons with diabetes (n = 906) was followed over a 4-year
      period. Education, occupational status, employment status, and marital status
      were measured at baseline and follow-up. Main outcome measures were incidence of
      proliferative retinopathy and loss of vision measured using standard protocols.
      RESULTS: Proliferative retinopathy was more likely to develop in younger-onset
      women with less education than in those with more education; no relation was
      found in the older-onset group. Education was associated inversely with incidence
      of loss of vision in younger-onset women and older-onset men. CONCLUSION: These
      data suggest that education is associated with the development of loss of vision,
      independent of other risk factors. The associations vary between men and women
      and between younger-onset and older-onset people with diabetes. Further
      understanding of these relationships may lead to interventions to prevent loss of
      vision in people with diabetes.

PMID- 8302567
TI  - Ocular factors in the incidence and progression of diabetic retinopathy.
AB  - PURPOSE: To investigate the association of intraocular pressure (IOP), ocular
      perfusion pressure, and myopia with the incidence and progression of diabetic
      retinopathy. METHODS: The design is a cohort study of a population-based sample
      (n = 1210) of persons with younger-onset diabetes (diagnosis was made before 30
      years of age, and subjects were taking insulin) and a random sample (n = 1780) of
      persons with older-onset diabetes (diagnosis made after 30 years of age).
      Baseline and 4-year follow-up examinations were completed by 891 younger-onset
      and 987 older-onset persons. Retinopathy was graded from stereoscopic fundus
      photographs. Endpoints were incidence of retinopathy, progression of retinopathy,
      and progression to proliferative diabetic retinopathy (PDR). Ocular perfusion
      pressure was calculated from IOP and blood pressure. Myopia was a refractive
      error of -2 diopters or less. RESULTS: In univariate analyses, ocular perfusion
      pressure was associated with incidence of retinopathy (P < 0.005), progression of
      retinopathy (P = 0.07), and progression to PDR (P < 0.001) in the younger-onset
      group but not in older-onset subjects taking or not taking insulin. Intraocular
      pressure and myopia were not associated with any endpoint in any group. Using
      logistic regression to control for covariates, ocular perfusion pressure was
      significantly associated only with incidence of retinopathy in younger-onset
      persons. The odds ratio for a 10-mmHg increase in ocular perfusion pressure was
      2.13 (95% confidence interval, 1.30-3.50). Also, myopia was protective for
      progression to PDR in younger-onset persons with an odds ratio of 0.40 (95%
      confidence interval, 0.18-0.86). CONCLUSIONS: These results suggest that pressure
      phenomena may be related to the development of retinopathy in younger-onset
      persons. This would have implications for treatments affecting both IOP and blood
      pressure.

PMID- 8302568
TI  - Optical treatment of residual vision in diabetic retinopathy.
AB  - PURPOSE: The purposes of this study of diabetic retinopathy are to classify
      degree of vision impairment, determine the percentage of patients for whom vision
      can be improved by an accurate refraction, identify the most useful magnifying
      devices, and arrive at the success rate for the magnifiers. METHODS: Study of 101
      consecutive subjects. RESULTS: Visual acuity was 20/200 (6/60) or better in 71%
      of subjects. Spectacle correction improved vision for 29%. High-add bifocal
      magnifiers improved vision for 30% of patients; half-eye spectacle magnifiers
      improved vision for 45%; and hand-held magnifiers improved vision for 11% of
      patients. Visolett magnifiers improved vision for 44%, and combination spectacle
      magnifiers and Visolett improved vision for 24% of patients. Multiple optical
      aids for 63% of patients resulted in a success rate of 68%. CONCLUSIONS: The
      ophthalmologist is obligated to ensure that eyes are refracted and appropriate
      magnifying devices are provided as part of treatment for diabetic retinopathy.

PMID- 8302569
TI  - Photodynamic therapy of experimental choroidal melanoma using lipoprotein
      delivered benzoporphyrin.
AB  - BACKGROUND: Benzoporphyrin derivative monoacid (BPD) is a new photosensitizer
      currently undergoing clinical trial for cutaneous malignancies. Compared with the
      clinically most frequently used sensitizer, Photofrin, BPD may offer higher tumor
      phototoxicity, better tissue penetration, and absence of significant skin
      sensitization. Low-density lipoprotein (LDL) carriers heighten efficiency and
      selectivity of BPD because neovascular and tumor cells express an increased
      number of LDL receptors. Hence, in addition to the vaso-occlusive effects similar
      to most other photosensitizers, LDL-BPD also has been shown to cause direct tumor
      cell damage. METHODS: Benzoporphyrin derivative monoacid was complexed with human
      LDL and used in photodynamic treatment of choroidal melanomas experimentally
      induced in eight albino rabbits. Five rabbits served as controls. Three hours
      after intravenous injection of 2 mg/kg body weight of LDL-BPD, eight tumors were
      irradiated at 692 nm and 100 J/cm2 via an argon-pumped dye laser coupled into a
      slit lamp. RESULTS: Angiography and histologic findings showed immediate
      photothrombosis after disintegration of endothelial membranes. After complete
      necrosis of tumor cells within 24 hours, a small fibrotic scar slowly developed.
      No tumor regrowth was noted up to 6 weeks when animals were killed. CONCLUSION:
      These data suggest that photodynamic treatment with LDL-BPD may be a promising
      modality for multiple clinical applications, including tumors and
      neovascularizations II.

PMID- 8302570
TI  - Overexpression of wild-type p53 interferes with normal development in Xenopus
      laevis embryos.
AB  - We have cloned and sequenced a Xenopus p53 homologue which differs by one amino
      acid deletion from a previously published Xenopus sequence (Soussi et al., 1987).
      Transcription analysis revealed that this gene is activated during early
      oogenesis and that zygotic transcription initiates after midblastula transition.
      Transcripts are also present in all tested tissues of adult animals. Whole mount
      in situ hybridization with Xenopus oocytes and embryos revealed, that transcripts
      are ubiquitously distributed although some accumulation is observed in certain
      tissues. Microinjection of p53 mRNA into early cleavage stages effectively
      resulted in overexpression of p53 protein and interfered with normal development.
      Lethal defects until and during gastrulation and aberrant phenotypes of surviving
      embryos were probably caused by cleavage arrest or cleavage delay of injected
      cells with subsequent distortions of cell movements, induction processes and
      tissue differentiations.

PMID- 8302571
TI  - Comparison of the expression and function of the transcription factor PU.1 (Spi-1
      proto-oncogene) between murine macrophages and B lymphocytes.
AB  - The expression of mRNA encoding the DNA-binding protein PU.1 (Spi-1) is
      restricted to B lymphocytes and macrophages. The role of PU.1 in tissue-specific
      transcriptional regulation in the two cell types was examined by co-transfection
      of a PU.1 expression plasmid with vectors containing B cell (IgH enhancer) or
      macrophage-specific (c-fms) transcription control elements. Cotransfection of the
      PU.1 expression plasmid in MOPC31C B cells trans-repressed the IgH enhancer but
      trans-activated the c-fms promoter. The latter was insufficient to overcome a
      block to transcription elongation that determines macrophage-specific c-fms gene
      expression. In the macrophage line RAW264, PU.1 had no effect on the c-fms
      promoter, but trans-repressed the activity of a c-fms reporter plasmid containing
      the transcription attenuator. The effects of PU.1 in both cell types were
      distinct from those of c-ets-2, a related factor, which trans-activated the c-fms
      promoter in both B cells and macrophages but also repressed the IgH enhancer.
      PU.1 was shown to be one of several nuclear proteins that bound a critical cis
      acting element of the IgH enhancer, microB, but analysis of nuclear extracts of a
      wide range of B cell and macrophage lines demonstrated a strong correlation
      between macrophage phenotype and nuclear PU.1 expression. The data suggest that
      differences in nuclear PU.1 expression and function between macrophages and B
      cells may play a role in lineage divergence.

PMID- 8302572
TI  - The viral and cellular Rel oncoproteins induce the differentiation of P19
      embryonal carcinoma cells.
AB  - Rel proteins have been implicated in the differentiation and transformation of
      lymphoid cells. Despite their significant sequence homology to the Drosophila
      Dorsal morphogen, a functional role for Rel proteins in early development has yet
      to be established. Here we show that expression of the v- or c-rel genes in P19
      embryonal carcinoma (EC) cells leads to drastic morphological changes accompanied
      by the expression of several differentiation-specific antigens. In contrast, v
      Rel mutants defective for DNA-binding as well as those lacking the F9 cell
      specific transcription activation region of v-Rel were equally unable to promote
      P19 cell differentiation. Our results demonstrate that transcriptional activation
      by Rel proteins correlates with Rel-induced differentiation of EC cells, and
      raise the intriguing possibility that Rel proteins may play an important role in
      early developmental processes.

PMID- 8302573
TI  - The SH2-like Akt homology (AH) domain of c-akt is present in multiple copies in
      the genome of vertebrate and invertebrate eucaryotes. Cloning and
      characterization of the Drosophila melanogaster c-akt homolog Dakt1.
AB  - The Akt proto-oncogene encodes a serine-threonine protein kinase whose
      carboxyterminal catalytic domain is closely related to the catalytic domains of
      all the known members of the protein kinase C (PKC) family. Akt, however, differs
      from PKC in its N-terminal region which contains a domain related distantly to
      the SH2 domain of cytoplasmic tyrosine kinases and other signalling proteins,
      which we have named Akt homology (AH) domain. Low stringency hybridization of a c
      akt AH probe to a panel of genomic DNAs from vertebrate and invertebrate
      eucaryotes detected multiple DNA bands (perhaps multiple genes) in all tested
      species. Drosophila DNA contains at least three hybridizing DNA bands. One of
      them was cloned, and found by sequence analysis, to define an Akt related gene
      (Dakt1). Comparison between the coding regions of c-akt and Dakt1 revealed 64.6%
      identity at the nucleotide level and 76.5% similarity at the amino acid level.
      The highest degree of homology was detected in the AH domain (68.3% similarity at
      the amino acid level) and the catalytic domain (83.3% similarity). Additional
      sequence comparisons revealed that the amino acid similarity between the
      catalytic domains of Dkt1 and the three known members of the Drosophila protein
      kinase C (PKC) family, Dpkc1, Dpkc2 and Dpkc3, is 68%, 63.6% and 67.1%,
      respectively. Dakt1 was mapped to Drosophila chromosome 3R 89BC. Its expression
      is subject to developmental regulation with the highest levels detected within
      the fourth hour of embryonic development. These results confirm that the AH
      domain of Akt defines new protein families in both vertebrate and invertebrate
      eucaryotes. The high degree of homology between the catalytic domains of Dkt1 and
      the three known members of the Drosophila PKC family suggests an evolutionarily
      conserved functional relationship between the members of the two families.

PMID- 8302574
TI  - Use of a temperature-sensitive mutant to define the biological effects of the
      p210BCR-ABL tyrosine kinase on proliferation of a factor-dependent murine myeloid
      cell line.
AB  - The Philadelphia chromosome, detected in virtually all cases of chronic
      myelogenous leukemia, is formed by a reciprocal translocation between chromosomes
      9 and 22 that fuses BCR encoded sequences upstream of exon 2 of c-ABL. This
      oncogene produces a fusion protein, p210BCR-ABL, in which the ABL tyrosine kinase
      activity is elevated. This elevated kinase activity is essential for
      transformation, but the mechanisms involved are unknown. To investigate p210BCR
      ABL function we constructed a model system in which the tyrosine kinase activity
      of p210BCR-ABL was inducible. Two amino acid substitutions, Arg to His at amino
      acid 457 and Tyr to His at amino acid 469 of c-abl, modeled on mutations known to
      render v-src temperature-sensitive for tyrosine kinase activity, were introduced
      into p210BCR-ABL. This mutant was characterized in an IL-3 growth factor
      dependent murine myeloid cell line, 32Dc13. Cell lines expressing the temperature
      sensitive mutant remained factor dependent at the non-permissive temperature, but
      at the permissive temperature displayed a marked reduction in cell death in the
      absence of growth factor and an exaggerated proliferative response to low levels
      of IL-3. Both the kinase activity of the mutant and the levels of tyrosine
      phosphorylated proteins are increased in the temperature-sensitive mutant at the
      permissive temperature. Further, tyrosine phosphorylation of potential substrates
      of the p210BCR-ABL tyrosine kinase, p120 rasGAP and its associated proteins of
      p190 and p62, only occurs at the permissive temperature in cells expressing the
      temperature-sensitive mutant.

PMID- 8302575
TI  - Overexpression of PDGF-B in murine hematopoietic cells induces a lethal
      myeloproliferative syndrome in vivo.
AB  - Although PDGF is not a primary hematopoietic cytokine, effects in hematopoietic
      cell cultures have been reported. We recently described responses of multilineage
      hematopoietic precursors to PDGF. The effects were shown to be neutralized by
      antibody to IL-1 beta and mediated by marrow macrophages that expressed PDGF
      receptor RNA and responded to PDGF by upregulation of IL-1 RNA. The present study
      was performed to determine whether constitutive expression of PDGF by
      hematopoietic cells would have hematopoietic consequences in vivo. Retroviral
      vectors containing a PDGF-B gene were constructed and infected into normal marrow
      cells. Irradiated mice reconstituted with infected cells consistently developed a
      lethal myeloproliferative syndrome with anemia, neutrophilia and monocytosis,
      declining hematopoiesis in marrow with shift to the spleen, and extensive
      infiltration of immature hematopoietic cells into the parenchymal organs and
      connective tissues. In addition to PDGF, the retroviral constructs expressed a
      neo resistance marker. Phenotypic expression patterns in fibroblasts and in
      hematopoietic colony-forming cells in vitro were consistent with a significant
      degree of interaction between the two expressed inserts. Moreover, selection of
      infected cells for G418 resistance significantly reduced not only the number of
      infected reconstituting cells but also the intensity of the evoked syndrome in
      vivo. The observations have important implications for projected gene therapy
      protocols, and identify a novel potential pathway to myeloproliferative disease.

PMID- 8302577
TI  - DNA synthesis-associated nuclear exclusion of p53 in normal human breast
      epithelial cells in culture.
AB  - Immunohistochemical staining using three monoclonal antibodies to p53 revealed
      that most normal human breast epithelial cells (HBEC) in the exponential growth
      phase, have p53 located in the nucleus but that some cells have the protein in
      the cytoplasm. Cytoplasmic staining of p53 with the monoclonal antibody PAb240
      was inhibited by the specific oligopeptide, NTFRHSVVVP, that corresponds to the
      amino acids between 210 and 219 in p53 and which includes the epitope domain for
      PAb240. It was not inhibited by the control oligopeptide SPFVTVHNVR. Growth
      arrest of HBEC achieved by EGF depletion resulted in predominant nuclear location
      of p53 and stimulation of arrested cells with EGF induced transient nuclear
      exclusion of the protein when the induced DNA synthesis level was maximal. These
      observations suggest that p53 in normal HBEC becomes inactivated by nuclear
      exclusion during cellular DNA synthesis.

PMID- 8302576
TI  - Highly conserved amino acids in the SH2 and catalytic domains of v-src are
      altered in naturally occurring, transformation-defective alleles.
AB  - We have identified 11 novel point mutations that abolish the transforming
      capacity of the oncogene v-src. These transformation-defective alleles were
      originally identified in morphologically flat subclones of rat cells transformed
      by wild type v-src. Nine of the mutations affect amino acid residues that are
      highly conserved in the catalytic domain of pp60v-src and completely abolish
      kinase activity. The other 2 mutations alter conserved residues in the SH2 domain
      (Phe-172 replaced with Val in one case [F172V] and Leu-186 replaced with Phe in
      the other [L186F]), drastically reducing, but not eliminating, kinase activity.
      The enzymatic and transforming functions of one of the SH2 mutants, L186F are
      host dependent; the mutant protein is active in chicken cells, but inactive in
      rat cells, as previously observed for some other SH2 mutants. These results are
      interpreted in relation to the recently described three-dimensional structures of
      SH2 domains and of the catalytic domain of a protein kinase. In addition, they
      support a role for the SH2 domain in the regulation of kinase activity.

PMID- 8302578
TI  - Examination of human tumors for rhoA mutations.
AB  - rhoA encodes a ras-related GTP-binding protein that is thought to play a role in
      cytoskeletal organization. Recent evidence has suggested both that rhoA could act
      either as a dominant oncogene, since transfection of both normal and activated
      rho genes confer a transformed phenotype on fibroblast cells in culture, or as a
      recessive tumor suppressor gene, by virtue, in part, of its chromosomal location
      at 3p21, a site deleted in many human malignancies. In either case, a role for
      rhoA in the oncogenesis of human tumors would be supported by the finding of rhoA
      mutations in tumors. We therefore examined human tumors and cell lines for
      mutations in the protein coding regions of rhoA by RNAase protection analysis. We
      first examined the expression of rhoA in renal cell carcinoma cell lines in which
      3p21 was heterozygously deleted or retained. We found no evidence for rhoA
      mutations in these specimens. We also examined RNA from lung, breast, colon or
      ovarian tumors and also found no evidence of activating rhoA mutations.
      Furthermore, there was no relation between the level of rhoA mRNA expression and
      the presence or absence of 3p21 deletions in the renal cell carcinoma specimens.
      Thus, although rhoA has transforming potential in vitro, there is no evidence
      that it is activated by mutation in human malignancies, or that it could act as a
      tumor suppressor gene in tumors in which 3p21 is deleted.

PMID- 8302579
TI  - Shb is a ubiquitously expressed Src homology 2 protein.
AB  - To identify serum-inducible genes in the insulin-producing cell line beta TC-1, a
      library subtraction screening procedure was performed on serum-deprived (G0) and
      serum-restimulated (G1) insulin-producing beta TC-1 cells. A cDNA containing a
      motif with strong homology to Src homology 2 (SH2) domains was found using this
      procedure and called Shb. The Shb cDNA contains two methionine codons in its N
      terminus and thus may code for two proteins of 67 and 56 kDa, each with one SH2
      domain in its C-terminus. No other structural similarity to proteins with
      catalytic activity could be detected, suggesting that Shb is a so called adaptor.
      Shb contains the proline-rich sequence PPPGPGR between the two proposed initiator
      methionines which resembles a sequence for binding to Src homology 3 (SH3)
      domains. A second proline-rich sequence was detected after the second methionine
      codon. The Shb cDNA hybridized to a similar or identical mRNA of 3.1 kb expressed
      in mouse brain, liver, kidney, heart, NIH3T3 fibroblasts and beta TC-1 cells.
      Western blot analysis of the same tissues using an antiserum directed against a
      synthetic peptide corresponding to a part of the SH2 domain of Shb, revealed
      reactivity with two proteins of 56 and 67 kDa. In addition, a third reactive
      component of 40 kDa was detected in most tissues. Transfection and transient
      expression of the Shb cDNA in COS-1 cells yielded increased expression of the 67,
      56 and 40 kDa proteins. Transfection and stable expression of the Shb cDNA in pig
      aortic endothelial cells showed increased expression primarily of the 67 kDa
      protein. A fusion protein consisting of the SH2 domain of Shb linked to
      glutathione S-transferase showed increased binding to glycoproteins of cells
      stimulated with platelet-derived growth factor (PDGF-BB). Furthermore, the
      autophosphorylated PDGF beta-receptor but not the autophosphorylated epidermal
      growth factor (EGF) receptor bound specifically to immobilized fusion protein. It
      is concluded that Shb is a novel SH2-containing protein with proline-rich domains
      and therefore probably involved in the signal-transduction of some ligand
      activated tyrosine kinase receptors.

PMID- 8302580
TI  - p53 overexpression is frequent in European hepatocellular carcinoma and largely
      independent of the codon 249 hot spot mutation.
AB  - Mutations in the p53 tumour suppressor gene have been recently described in
      hepatocellular carcinomas (HCC) from high risk areas such as China and South
      Africa. Our study was designed to assess the importance of p53 aberrations in
      HCCs from Europe, where the major risk factors in hepatocarcinogenesis, aflatoxin
      exposure and chronic hepatitis B virus (HBV) infection, do not play a dominant
      role. We investigated 22 HCCs and, as controls, their corresponding tumour-free
      liver tissues, seven livers with primary biliary cirrhosis and four
      morphologically normal livers. p53 overexpression, which is usually associated
      with point mutations of the p53 gene, was detected in 10 of the 22 HCCs by
      immunoblotting and immunohistochemistry. p53 expression was restricted to the
      nucleus in the positive cells, while all cells in the control tissues were
      negative. There was no obvious etiological preference in the p53 positive
      tumours. Particularly, underlying chronic HBV infection did not appear to be
      associated with an increased rate of p53 overexpression in European HCCs. SSCP
      and sequence analysis of exons 5-8 of the p53 gene revealed point mutations in
      six out of eight tumours with increased steady state levels of p53. In
      conclusion, our study demonstrates increased p53 levels due to point mutations in
      a significant proportion of European HCCs. The codon 249 mutation, which was
      detected in one of the cases, is not predominant in these tumours.

PMID- 8302581
TI  - p53 mutations in HPV-negative cervical carcinoma.
AB  - Human papillomavirus (HPV) infection has been strongly linked to the development
      of cervical carcinoma. Two viral oncoproteins, E6 and E7, produced by HPV, have
      been shown to immortalize primary human genital epithelial cells by interacting
      with the protein products of cellular tumor suppressor genes p53 and Rb,
      respectively. E6 binds to the cellular p53 protein promoting p53 degradation and
      inactivity. This mechanism has been suggested to contribute to the oncogenesis of
      HPV-positive anogenital cancers. In HPV-negative cervical carcinoma, p53 mutation
      is thought to be the possible mechanism of oncogenesis. We have studied 257
      cervical carcinoma specimens for HPV infection by Southern blot analysis and
      polymerase chain reaction (PCR). Of 257 samples, 39 were HPV-negative. We have
      further studied 21 HPV-negative specimens for p53 mutations utilizing PCR
      amplification of genomic DNA followed by single-stranded conformation
      polymorphism (SSCP) analysis and DNA sequencing. We found only two missense point
      mutations of p53 gene. In summary, although inactivation of p53 mediated either
      by E6 or by mutations may be an important key step in the development of cervical
      carcinoma, our study suggests that other mechanisms may also be involved in
      development of cervical cancer.

PMID- 8302582
TI  - Identification and chromosomal mapping of a receptor tyrosine kinase with a
      putative phospholipid binding sequence in its ectodomain.
AB  - We have cloned a novel receptor tyrosine kinase that has an unusual ectodomain.
      The extracellular sequence consists of 416 amino acids and has none of the
      structural motifs that have been found in other receptor tyrosine kinases. The
      150 amino acids in the amino terminus of the receptor is homologous to a putative
      phospholipid-binding sequence that is found also in other cell adhesion molecules
      such as the neuronal A5 antigen and coagulation factors V and VIII. The kinase
      domain has a short cytoplasmic tail and contains a short insert between
      subdomains I and II. The structure of this receptor kinase suggests that it
      belongs to a new family of receptors involved in cell-cell interactions. The cell
      adhesion kinase (Cak) is expressed at low levels in most adult tissues and
      expression is highest in the brain and lung. Using fluorescence in situ
      hybridization and interspecific backcross mapping, the Cak gene was localized to
      human chromosome 6 and mouse chromosome 17.

PMID- 8302584
TI  - Identification of a second promoter in the human c-myb proto-oncogene.
AB  - We have previously described an alternatively spliced cDNA clone of the human c
      myb proto-oncogene which has been shown to enhance the differentiation of Friend
      murine erythroleukemia cells. This clone, pMbm-2, contains unique 5' sequences
      which replace exon 1. The human c-myb intron 1 was sequenced to determine the
      exact position of this unique sequence and to further characterize the role of
      intron 1 in the regulation of the human c-myb gene. Here we report that intron 1
      of c-myb is highly conserved between human and mouse throughout the intron, while
      only those sequences directly adjacent to exons 1 and 2 are conserved between
      human and chicken. The unique sequence of pMbm-2 was located directly adjacent to
      exon 2, suggesting that it arose as a product of alternative transcription
      initiation within intron 1. RNAase protection analysis was used to map a cluster
      of transcription start sites at the 5' end of exon 2. Levels of messages
      utilizing these start sites are proportional to those arising from the primary
      promoter. Functional characterization of this region revealed that this region
      can function as a promoter. Deletion studies have revealed the presence of
      negative and positive regulatory elements within this region which are utilized
      with different efficiencies in different cell lines. These studies suggest that
      cis or trans factors acting in this region may serve a dual function in both
      attenuation and transcription initiation.

PMID- 8302583
TI  - Epithelial tumours induced by a herpesvirus oncogene in transgenic mice.
AB  - To investigate the role of herpesviral genes in tumourigenesis, transgenic mice
      were generated expressing STP-C, a transformation associated protein of the
      lymphoma inducing herpesvirus saimiri. Epithelial tumours developed in the
      salivary gland, pancreas, thymus and liver of transgenic mice within the first
      weeks of life. Thus, the target cells for tumour formation in the transgenic mice
      were surprisingly different from those of the herpesvirus from which the oncogene
      was derived. Our results identify STP-C as a herpesvirus oncogene sufficient for
      tumour induction without the cooperation of other viral gene products.
      Furthermore, the results demonstrate pleiotropic transforming capabilities of the
      STP-C oncogene and suggest that the specificity of lymphoma induction by the
      virus is determined by factors other than the oncogene itself.

PMID- 8302585
TI  - c-Myb prevents TPA-induced differentiation and cell death in v-Myb transformed
      monoblasts.
AB  - Myelomonocytic cells transformed by v-Myb or altered forms of c-Myb do not
      contain the full-length c-Myb protein found in most immature hematopoietic cells.
      To determine if c-Myb was a dominant inhibitor of v-Myb, we have induced the
      synthesis of full-length c-Myb in monoblasts transformed by v-Myb. We found that
      although some morphological changes occurred, the presence of both c-Myb and v
      Myb was compatible with cell growth. However, the response to phorbol ester (TPA)
      was significantly altered by c-Myb. Monoblasts transformed by v-Myb can be
      induced to differentiate into macrophages by treatment with TPA. This process is
      accompanied by a significant amount of cell death. However, when c-Myb was made
      TPA-inducible in these cells, TPA-induced differentiation into macrophages was
      blocked and cell death was prevented. These results demonstrate a significant
      difference in the biological effects of v-Myb and c-Myb in transformed
      myelomonocytic cells.

PMID- 8302586
TI  - A novel c-myc-activating reciprocal T(12;15) chromosomal translocation juxtaposes
      S alpha to Pvt-1 in a mouse plasmacytoma.
AB  - Oil-induced murine plasmacytomas typically carry c-myc-activating non-random
      reciprocal chromosomal translocations that take the form of either a T(12;15)
      that fuses the c-myc proto-oncogene to an immunoglobulin heavy chain switch
      region or a T(6;15) that juxtaposes the Pvt-1 locus, located 220 kb 3' of c-myc,
      to the immunoglobulin light china locus, C kappa. In this report we show that the
      plasmacytoma ABPC 60 harbors a novel c-myc-activating T(12;15) in which the
      chromosome 15 breakpoint occurs in the Pvt-1 region, resulting in the head-to
      tail juxtaposition of the Pvt-1 major breakpoint cluster to the IgA switch
      region. Restriction mapping and nucleotide sequencing of this atypical
      translocation indicate that a paracentric inversion in chromosome 12 must have
      preceeded the translocation. This is the first example of a T(12;15) with a break
      3' of the c-myc gene. The rearrangement places the 3' C alpha enhancer (3' alpha
      E) greater than 200 kb downstream of the c-myc promoters, however c-myc mRNA
      levels are similar to those observed in plasmacytomas with typical T(12;15)s that
      translocate 3' alpha E much closer (15-25 kb) and upstream of c-myc. The up
      regulation of c-myc that results from this rearrangement is thought to be brought
      about by the interaction of the c-myc promoters with the IgA enhancer element
      that has been strategically relocated into the Pvt-1 region.

PMID- 8302587
TI  - Microcell-mediated transfer of chromosome 6 into metastatic human C8161 melanoma
      cells suppresses metastasis but does not inhibit tumorigenicity.
AB  - Structural alterations of chromosome 6, including del(6q), are often associated
      with metastatic melanoma; therefore, we hypothesized that a metastasis-suppressor
      gene could be coded on human chromosome 6. Highly metastatic C8161 human
      malignant melanoma cells exhibit chromosomal changes typical of late-stage
      melanomas. Using microcell-mediated chromosome transfer, a copy of a normal human
      chromosome 6 was introduced into C8161. Three randomly selected hybrid clones
      (neo6/C8161.1, neo6/C8161.2 and neo6/C8161.3) were assayed for metastasis in
      athymic nude mice. All controls - parental C8161 cells, randomly-selected single
      cell clones, neo-transfected cell clones, neo11/C8161.2 and neo11/C8161.3 - were
      tumorigenic (270/272 mice) and metastatic (208/272 mice). neo6/C8161 hybrid cells
      were still tumorigenic (91/93 mice) but were not metastatic (0/195 mice). The
      presence of the added chromosomes was verified in cultured and tumor cells by
      amplification of polymorphic (CA)n markers using PCR-RFLP. The neo6/C8161 hybrids
      display growth and morphological patterns of more differentiated cells than
      C8161. In Northern blot analysis an inverse relationship between metastatic
      ability and metastasis-suppressor gene, nm23-H1, expression is observed - with
      clone neo6/C8161.1 expressing the highest level of nm23 transcripts, neo6/C8161.2
      and neo6/C8161.3 expressing intermediate levels, and barely detectable levels are
      seen in C8161. Collectively, these results suggest that a malignant melanoma
      metastasis-regulatory gene may be located on human chromosome 6. These results
      further demonstrate that tumorigenicity and metastatic ability are distinct
      phenotypes.

PMID- 8302588
TI  - Directional selection associated with clonal expansion of p53 mutant cells during
      neoplastic development of carcinogen-treated rat embryo lung epithelial cells.
AB  - In this study, rat embryo lung organ cultures were exposed to benzo[a]pyrene
      (B[a]P). After carcinogen-treatment the cells were dissociated and an epithelial
      cell line (BP) was developed from the primary cell culture derived from the
      carcinogen-treated explants. Investigations were performed on the sequential
      changes occurring in the course of neoplastic progression of BP cells and in the
      tumor cells that arose in vivo from implanted BP cells. During the neoplastic
      progression a mutation was shown to occur in p53 gene at codon 130 (AAG > AGG;
      Lys > Arg) in a single cell which expanded and gave rise to a predominant
      subpopulation. This mutational event was already detected at passage 14 but was
      probably not a direct consequence of a specific alteration caused by the
      carcinogen in the target cell. This mutation was retained through the subsequent
      progressional steps first as a heterozygous mutation, then converted to a
      homozygous state. From passage 18 on, it was possible in BP cell cultures to
      detect foci of larger morphologically distinct cells emerging on a background of
      cells maintaining the original morphology. These foci were shown to derive from a
      single cell carrying the p53 mutation in a homozygous state. During the
      neoplastic progression the mutant p53 allele frequency steadily increased and
      this mutant allele eventually came to predominate completely in the late stages
      of the neoplastic progression, including in the transplantation-induced tumors.
      The pattern of a directional selection for mutant p53 gene towards fixation is
      probably applicable to a wide range of human malignancies and may reflect the
      particular importance of this gene for tumorigenesis.

PMID- 8302589
TI  - Involvement of Rho p21 small GTP-binding protein and its regulator in the HGF
      induced cell motility.
AB  - Hepatocyte growth factor (HGF) induced motility of cultured mouse keratinocytes
      (308R cells). This HGF-induced cell motility was inhibited by microinjection of
      either rho GDI, an inhibitory GDP/GTP exchange protein for rho p21 small GTP
      binding protein, or a botulinum exoenzyme C3 which is known to selectively impair
      the function of rho p21 by ADP-ribosylating its effector domain. The rho GDI
      action was prevented by comicroinjection with the guanosine 5'-(3-0
      thio)triphosphate (GTP gamma S)-bound active form of rhoA p21, and the C3 action
      was prevented by comicroinjection with a rhoA p21 mutant (rhoAIle41 p21) which is
      resistant to the C3 action. The HGF-induced cell motility was not inhibited by
      microinjection of a dominant negative rac1 p21 mutant (rac1Asn17 p21) or a
      dominant negative Ki-ras p21 mutant (Ki-rasAsn17 p21). Microinjection of the GTP
      gamma S-bound form of rac1 p21 or a dominant active Ki-ras p21 mutant (Ki
      rasVal12 p21) did not induce cell motility. These results indicate that both rho
      p21 and rho GDI, but neither rac p21 nor ras p21, are involved in the HGF-induced
      cell motility. However, microinjection of the GTP gamma S-bound form of rhoA p21
      alone did not induce cell motility in the absence of HGF, suggesting that
      activation of rho p21 is necessary but not sufficient for the HGF-induced cell
      motility. The HGF-induced cell motility was mimicked by 12-0-tetradecanoyl
      phorbol-13-acetate, a protein kinase C-activating phorbol ester, but not by Ca2+
      ionophore. The phorbol ester-induced cell motility was also inhibited by
      microinjection of rho GDI or C3. These results indicate that both rho p21 and rho
      GDI are also involved in the phorbol ester-induced cell motility.

PMID- 8302590
TI  - In vitro reconstruction of tumour initiation in a human epithelium.
AB  - Knowledge of tumour initiation in human epithelia is limited by sample
      availability and difficulty in experimental manipulation of human cells. The
      thyroid is a useful model since, in addition to multiple tumour stages, it
      presents two distinct 'pathways' of tumorigenesis: 'follicular' tumours, in which
      ras oncogene mutations occur at high frequency and 'papillary' tumours,
      associated with ret (or trk) activation. We have used these observations to
      reconstruct early thyroid tumorigenesis, using amphotropic retroviral vectors.
      When introduced into normal thyroid epithelial cells, mutant ras induces self
      limiting growth of well-demarcated, differentiated colonies--a phenotype
      consistent with follicular adenoma. Activated ret on the other hand induces
      smaller, poorly-demarcated colonies with a morphology consistent with early
      papillary tumours. Mutant p53--which occurs only in the latest stages of thyroid
      cancer--was without effect. Our results provide the first direct experimental
      evidence in a human epithelium for alternative initiating oncogenes and their
      determination of the subsequent 'direction' of tumour development.

PMID- 8302591
TI  - Microsatellite instability occurs frequently in human gastric carcinoma.
AB  - Microsatellites are short repeated oligonucleotide sequences found throughout the
      human genome. Microsatellite instability has been reported in hereditary and
      sporadic colorectal carcinomas. Since gastric carcinoma shares numerous molecular
      abnormalities with colon cancer, we evaluated 52 gastric adenocarcinomas and
      adjacent dysplastic tissues for microsatellite instability at five chromosomal
      loci. Instability at one or more loci was observed in 16 (31%) of the 52 tumors,
      but in only two dysplastic tissues adjacent to their respective tumors. These
      results demonstrate that microsatellite instability is not limited to colorectal
      carcinoma, but also occurs frequently in another cancer, that of the stomach. It
      is probably a late event, developing only rarely in premalignant dysplastic
      lesions.

PMID- 8302592
TI  - Inhibition of CRIPTO expression and tumorigenicity in human colon cancer cells by
      antisense RNA and oligodeoxynucleotides.
AB  - CRIPTO is an epidermal growth factor-related gene expressed in a majority of
      human colorectal tumors. To assess the role of CRIPTO in the growth control of
      human colon cancer, we have treated human colon carcinoma GEO and CBS cells, that
      possess high levels of CRIPTO, and WIDR colon cancer cells, that are negative for
      CRIPTO expression, with two antisense phosphorothioate oligodeoxynucleotides
      complementary to the 5' end of the human CRIPTO mRNA. Both antisense
      oligodeoxynucleotides significantly reduced endogenous CRIPTO protein levels and
      inhibited GEO and CBS cell growth in monolayer and in semisolid medium, whereas
      they did not affect WIDR cell growth. In addition, GEO, CBS and WIDR cells were
      infected with a recombinant retroviral vector containing the hygromycin
      resistance gene and a 900 bp EcoRI-EcoRI coding fragment of the human CRIPTO cDNA
      oriented in the 3' to 5' direction. GEO and CBS CRIPTO antisense infectants
      exhibited a 60 to 70% reduction in CRIPTO protein expression, in monolayer growth
      and in soft agar cloning efficiency as compared to parental noninfected cells. In
      contrast, infection of WIDR cells with the CRIPTO antisense retrovirus did not
      alter their growth. Finally, GEO CRIPTO antisense infectants formed tumors in
      nude mice that were significantly smaller and had a larger latency period as
      compared to noninfected GEO cells.

PMID- 8302593
TI  - Analysis of p53 quaternary structure in relation to sequence-specific DNA
      binding.
AB  - Quaternary interactions of p53 influence its tertiary structure which, in turn,
      is critical for sequence-specific DNA binding and tumour suppressor function.
      Given its regulatory potential we have sought to define the quaternary structure
      of p53 involved in sequence-specific DNA binding. Double stranded DNA [5'
      GGACATGCCCGGGCATGTCC-3'; Funk et al. (1992) Mol. Cell. Biol., 12, 2866-2871] was
      used to test p53 binding capacity in vitro. The p53 protein was translated in
      vitro and size fractionated prior to the DNA binding reaction. Two independent
      DNA binding assays were employed. The first detected electromobility shift of 32P
      labelled DNA and was carried out in the presence of PAb421, which stabilises and
      supershifts p53-DNA complexes. The second detected 35S-labelled p53 bound to
      biotinylated target DNA in the absence of PAb421. Sequence-specific DNA binding
      was found to be a property of full length, oligomeric p53. Greatest binding
      activity involved tetramers and/or higher molecular weight forms of p53, minimal
      binding was observed for dimers. This size profile was unaffected by PAb421 and
      it therefore seems unlikely that PAb421 dissociates high molecular weight forms
      of p53 into dimers. We conclude that high molecular weight forms of p53 are the
      most effective structures for sequence-specific DNA binding in vitro; these
      structures may represent tetramers and/or heterogeneous complexes of p53 with
      other proteins.

PMID- 8302594
TI  - Detection of proteins that bind to the leucine zipper motif of c-Myb.
AB  - The product of the c-myb proto-oncogene, c-Myb, binds DNA and can enhance
      transcription of genes bearing copies of the DNA sequence it recognises. Deletion
      or disruption of a negative regulatory domain (NRD) in the carboxyl portion of c
      Myb results in enhanced transactivating capacity and in parallel, leads to
      activation of its ability to transform haemopoietic cells. Since mutational
      analysis has shown that one critical element within the NRD is a leucine zipper
      motif, we have sought to identify cellular proteins that can interact with the c
      Myb leucine zipper. Using fusion proteins containing this region as an affinity
      reagent, we have identified two nuclear proteins, p67 and p160, that bind to the
      wild-type, but not to a mutated c-Myb leucine zipper. These two proteins were
      shown to be related by comparison of peptides generated by partial digestion.
      While p160 was found to be ubiquitous amongst different murine haemopoietic cell
      lines, and was also present in NIH3T3 fibroblasts, p67 was detected in a
      restricted set of immature myeloid cells. Intriguingly p160, but not p67, could
      also bind to the c-Jun leucine zipper.

PMID- 8302595
TI  - Identification and biochemical characterization of secreted Wnt-1 protein from
      P19 embryonal carcinoma cells induced to differentiate along the neuroectodermal
      lineage.
AB  - Previous studies have described Wnt-1 protein synthesized by cell lines
      transfected with Wnt-1 cDNA. This report presents the first identification and
      biochemical characterization of native Wnt-1 protein, from P19 embryonal
      carcinoma cells undergoing neuroectodermal differentiation. The data demonstrate
      that P19 cells efficiently process and secrete glycosylated Wnt-1 protein species
      of 40 kD and 42 kD. Similar to recombinant Wnt-1 proteins, native Wnt-1 proteins
      are associated with the cell surface upon secretion and can be released by
      suramin treatment of the cells. Non-reducing gel analysis showed that Wnt-1
      proteins are secreted as monomers.

PMID- 8302596
TI  - Transcellular activation of the HTLV promoter by human hematopoietic cells.
AB  - We examined the ability of hematopoietic cells to transactivate the HTLV promoter
      by a transcellular mechanism. HeLa cells containing a CAT reporter gene driven by
      the HTLV-2 promoter were cocultivated with hematopoietic cells of the B-(Raji), T
      (HuT78, Jurkat) and monocyte/promyelocytic (THP-1, U937 and HL60) lineages.
      Cocultivation with U937 and HuT78 cells constitutively and significantly
      transactivated the HTLV-2 promoter, while no effect was observed with the other
      lines. However, activation of other T-cell lines (CEM, Jurkat, Molt-3 and MT-4)
      with a combination of phorbolester and phytohemagglutinin also resulted in potent
      transactivation. Supernatant from HuT78 cells exhibited detectable
      transactivating activity, suggesting that the activation is mediated by a
      secreted factor(s). This factor also transactivates the HTLV-1 promoter. We used
      a panel of HTLV-1 LTR deletion mutants to map the responsive elements to this
      factor(s). Unlike the response element to the HTLV transactivator protein, Tax,
      which can be mapped to a small region in the enhancer, maximal transactivation by
      the cellular factor(s) required the complete U3 sequence. Transcellular
      activation of the HTLV promoter by activated T-cells may play a role in the
      development of leukemia in HTLV infected individuals.

PMID- 8302597
TI  - Oncogenic activity of cyclin D1 revealed through cooperation with Ha-ras: link
      between cell cycle control and malignant transformation.
AB  - Circumstantial evidence implicates the putative cell cycle regulator cyclin D1 in
      the process of malignant transformation. Overexpression of cyclin D1 is observed
      in mammary carcinomas as a result of gene amplification and in parathyroid
      adenomas and centrocytic B-cell lymphomas as a consequence of chromosomal
      rearrangements and juxtaposition of the cyclin D1 gene to strong transcriptional
      control elements. These findings suggest that deregulation of cyclin D1
      expression may contribute to malignant transformation in these tumours. To date,
      however, an oncogenic potential of cyclin D1 has not been demonstrated and the
      mechanism of its oncogenic activation remains obscure although overexpression of
      the wild-type protein is likely. We report here that the overexpression of cyclin
      D1 induces transformation in primary rat embryo fibroblasts in cooperation with
      activated Ha-ras. Cyclin D1/Ha-ras transformed cells are immortalized, show
      anchorage independence and give rise to fibrosarcomas in nude mice. Our data
      directly demonstrate that cyclin D1 is a proto-oncogene that can be activated by
      transcriptional deregulation. Its previously demonstrated ability to interact
      with putative cell cycle regulators suggests that cyclin D1 defines a new class
      of proto-oncogenes.

PMID- 8302598
TI  - Polymorphism at codon 36 of the p53 gene.
AB  - A polymorphism at codon 36 in exon 4 of the p53 gene was identified by single
      strand conformation polymorphism (SSCP) analysis and direct sequencing of genomic
      DNA PCR products. The polymorphic allele, present in the heterozygous state in
      genomic DNAs of four of 100 individuals (4%), changes the codon 36 CCG to CCA,
      eliminates a FinI restriction site and creates a BccI site. Including this
      polymorphism there are four known polymorphisms in the p53 coding sequence.

PMID- 8302599
TI  - p130gag-fps disrupts gap junctional communication and induces phosphorylation of
      connexin43 in a manner similar to that of pp60v-src.
AB  - The pp60v-src tyrosine kinase disrupts gap junctional communication in
      transformed fibroblasts and induces the phosphorylation of the gap junction
      protein, connexin43, on tyrosine. We report here that the p130gag-fps tyrosine
      kinase also profoundly disrupted gap junctional communication and markedly
      increased the phosphorylation of connexin43 which appeared to result from an
      accumulation of phosphotyrosine and phosphoserine. The disruption of gap
      junctional communication by pp60v-src and p130gag-fps did not appear to result
      from the gross alteration of gap junction plaques. Furthermore, two-dimensional
      phosphotryptic peptide mapping showed that the v-Src and V-Fps kinases stimulated
      the phosphorylation of multiple connexin43 peptides which contained
      phosphotyrosine and/or phosphoserine. Phosphotyrosine was detected in two
      connexin43 phosphotryptic peptides from v-src-tranformed cells which suggested
      that more than one connexin43 tyrosine site may be recognized by pp60v-src in
      fibroblasts. The apparent higher levels of phosphoserine-containing connexin43
      peptides in the oncogene-transformed cells pointed to the possibility that pp60v
      src and p130gag-fps may also modulate connexin43 function through mechanism(s)
      involving the activation of signaling serine kinases. Taken together, these
      results suggested that connexin43 is a common target of the v-Src and v-Fps
      tyrosine kinase oncoproteins.

PMID- 8302600
TI  - Analysis of a variant Max sequence expressed in Xenopus laevis.
AB  - Max is a small helix-loop-helix protein which forms heterodimers with members of
      the Myc protein family. Myc/Max heterodimers exhibit sequence-specific DNA
      binding with much greater affinity than Myc homodimers. The Xenopus laevis
      homologue of Max, XMax, is shorter than the equivalent mammalian protein. This
      difference results from the deletion of a 24 amino acid sequence located near the
      C-terminus of the protein. Xenopus max transcripts undergo alternative splicing.
      In addition to the 27 base alternatively spliced sequence (exon A) previously
      detected in mice and humans, some Xmax transcripts also contain an 81 base
      sequence (exon B) at a second site within the coding sequence. Although exon B
      insertion alters part of the leucine zipper protein/protein interaction domain,
      the resulting XMax protein retains the ability to form stable heterodimers with
      both c-Myc and N-Myc. Xmax mRNA is present at approximately constant levels
      during early development. This contrasts with the rapidly changing levels of c
      myc and N-myc mRNA in the embryo and has implications for regulation of gene
      expression during differentiation. All four alternatively spliced forms of Xmax
      mRNA are present during development and in all adult tissue examined.

PMID- 8302601
TI  - Two distinct regions form a functional activation domain of the HTLV-1 trans
      activator Tax1.
AB  - Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is an enigmatic viral
      transactivator that regulates expression of the viral gene and also several
      cellular genes normally controlled by various mitogenic signals. However,
      previous studies have failed to define the functional domains of Tax1 for
      enhancer specificities and for transcriptional activation (95% of the protein
      portion was indispensable for the activation function). This complexity has
      hampered understanding of the molecular basis of Tax1 action. In this study, we
      analysed the activation function of a Tax1 fused to the heterologous DNA-binding
      domain of the yeast transcription factor GAL4 and dissected the domain required
      for the activation function by using derivatives of a Tax1 mutant with an
      insertion between amino acids (a.a.) 170 and 171. Analysis of the derivatives of
      the mutant fusion protein having various partial overlaps encompassing the
      interrupted site suggested that two contiguous stretches, AD-I (2-255 a.a.) and
      AD-II (227-337 a.a.), should be both intact for the activation function of Tax1
      and that they form a functional activation domain.

PMID- 8302602
TI  - DNA aberrations at the retinoblastoma gene locus in human squamous cell
      carcinomas of the lung.
AB  - We detected DNA aberrations at the RB locus in surgical specimens of human
      primary non-small cell lung carcinoma by single-strand conformation polymorphism
      analysis of polymerase chain reaction products amplified from regions of exons 2
      to 27 including parts of the flanking intron sequences. Detection of nucleotide
      sequence polymorphism revealed loss of heterozygosity in six of eight informative
      cases among 13 squamous cell carcinomas analysed. In two of the six cases,
      mutations in the remaining allele were detected. In 25 adenocarcinomas analysed,
      no loss of heterozygosity was observed in 16 informative cases and a point
      mutation was detected in one of the uninformative cases. In one of three
      adenosquamous carcinomas analysed, a point mutation was detected and one adenoid
      cystic carcinoma analysed showed allelic loss of the RB gene. Our results
      indicated that loss of heterozygosity at the RB locus is frequent in squamous
      cell carcinomas of the lung, but not in adenocarcinomas. In the squamous cell
      carcinomas with allelic loss, mutations of the RB gene in the remaining alleles
      were found in one third of the tumors.

PMID- 8302603
TI  - Tyrosines1234-1235 are critical for activation of the tyrosine kinase encoded by
      the MET proto-oncogene (HGF receptor).
AB  - The tyrosine kinase encoded by the MET proto-oncogene (p190MET) is the receptor
      for Hepatocyte Growth Factor/Scatter Factor (HGF/SF). Previous work has shown
      that autophosphorylation of p190MET enhances its enzymatic activity and that the
      major phosphorylation site is Tyr1235, located in the catalytic domain. This
      residue is part of a 'three tyrosine' motif, including Tyr1230, Tyr1234, and
      Tyr1235, conserved in several other receptor kinases. We studied the role of
      these tyrosines in the positive regulation of the p190MET kinase by site-directed
      mutagenesis. Substitution of either Tyr1235 or Tyr1234 with phenylalanine
      severely reduced the in vitro kinase activity toward exogenous substrates.
      Kinetic experiments showed that the residual activity of these mutants could
      still be enhanced by autophosphorylation. Phosphopeptide mapping indicated that,
      in the absence of Tyr1235, Tyr1234 is phosphorylated. Only the replacement of
      both Tyr1234 and Tyr1235 yielded a mutant which completely lost the ability to be
      activated by autophosphorylation. In stable transfectants expressing the HGF/SF
      receptor with single substitution of either Tyr1234 or Tyr1235 the response to
      HGF/SF was impaired. The ligand did not induce tyrosine phosphorylation of the
      receptor nor stimulated chemotaxis. These data show that Tyr1234 and Tyr1235 are
      critical for the activation of the HGF/SF receptor kinase both in vitro and in
      response to the ligand in intact cells.

PMID- 8302604
TI  - Site-specific modulation of c-Myc cotransformation by residues phosphorylated in
      vivo.
AB  - c-Myc is a nuclear phosphoprotein which binds DNA as a heterodimer with Max. We
      have identified two in vivo phosphorylation sites, Thr58 and Ser62, within a
      domain highly conserved among all Myc family members. Thr58 is mutated in several
      viral forms of the protein and constitutes a mutational hot-spot in Burkitt's
      lymphoma. Members of the GSK-3 and MAP kinase families, but not CKII,
      specifically phosphorylated these sites in vitro. The effect of these
      phosphorylation sites on Myc function was assessed by cotransformation of primary
      rat embryo fibroblasts with Ras. Mutagenesis of Thr58 to alanine potentiated
      focus formation, whereas substitution of Ser62 severely inhibited transformation.
      Mutation of both residues restored wild-type activity. These data suggest acute,
      post-translational modulation of Myc via phosphorylation of a conserved region
      previously implicated in transactivation, transformation and autorepression.

PMID- 8302605
TI  - CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent
      kinases that associate with cyclin D1.
AB  - Deregulated expression of cyclin D1 is a feature of several neoplastic and
      proliferative disorders, but its normal role in the cell cycle remains unclear.
      Here we show that in a squamous carcinoma cell line with 11-fold amplification of
      the CCND1 gene, cyclin D1 associates specifically with p33cdk4 (PSK-J3) and
      p38cdk6 (PLSTIRE), two closely related members of the cyclin-dependent kinase
      (CDK) family. In these tumour cells, there is little evidence for an association
      between cyclin D1 and other CDKs, but in diploid human fibroblasts both CDK2 and
      CDK5 can be co-precipitated with cyclin D1, as well as CDK4. The data suggest
      that D-type cyclins participate in multiple interactions with CDKs but that the
      nature or stoichiometry of these associations may differ in different types of
      cell.

PMID- 8302606
TI  - Insertional activation of mevalonate kinase by hepatitis B virus DNA in a human
      hepatoma cell line.
AB  - Insertional mutagenesis of growth related genes by hepatitis B virus (HBV) DNA is
      presumed to play a role in hepatocarcinogenesis. Here, we report on insertional
      activation of the mevalonate kinase (MK) gene in the human hepatoma cell line
      PLC/PRF/5. Integration of HBV DNA dissociated the promoter and upstream
      regulatory elements of the gene from its coding sequences. This led to the over
      expression of hybrid transcripts arising from an HBV promoter and the consequent
      over-production of functionally active mevalonate kinase. MK phosphorylates
      mevalonate, a major intermediate in the branched cholesterol/isoprenoid
      biosynthetic pathway. Isoprenylation is crucial to the functions of cellular
      proteins related to growth control, including the proto-oncogene ras. As the
      enzymes of these biosynthetic pathways are regulated at multiple points by
      negative feedback, both transcriptionally and at the protein level, the results
      discussed here support the idea that aberrant growth could result from
      deregulated overexpression of MK and, perhaps, other enzymes in the cholesterol
      pathway. These results invoke novel mechanisms by which cell transformation might
      occur.

PMID- 8302607
TI  - Cell cycle dependent regulation of the protein kinase TTK.
AB  - TTK is a novel protein kinase detectable in all proliferating human cells and
      tissues. Expression of the TTK gene is markedly reduced or absent in resting
      cells and in tissues with a low proliferative index. In view of the apparent
      association between TTK gene expression and cell proliferation, we examined the
      regulation of this protein kinase during transit of the cell cycle. We found very
      low levels of TTK mRNA and protein in starved cells. When cells are induced to
      enter the cell cycle, levels of TTK mRNA, protein and kinase activity increase at
      the G1/S phase of the cell cycle and peak in G2/M. TTK mRNA levels, as well as
      kinase activity, drop sharply in early G1, whereas protein levels are largely
      maintained. TTK may play a role in cell cycle control.

PMID- 8302608
TI  - Splice-site mutation of the p53 gene in a family with hereditary breast-ovarian
      cancer.
AB  - Germline mutations within evolutionary conserved exons of the p53 gene predispose
      to tumor development in several familial cancer syndromes. We now report
      identification of a novel p53 mutation affecting the splice acceptor site of exon
      6 in the germline DNA of a family with hereditary breast-ovarian cancer. This
      splice-site mutation, which results in omission of exon 6 and creates a frame
      shift and premature stop codon in transcripts from the mutant allele, was found
      in seven family members--four of whom have developed breast, ovarian or choroid
      plexus tumors before age 35. Our finding suggests the need to examine the entire
      p53 gene for splice-site, frame-shift, and nonsense (as well as missense)
      mutations in families with early-onset hereditary breast and breast-ovarian
      cancers not linked to the BRCA1 gene on chromosome 17q. We propose that the term
      'p53 familial cancer syndrome' be applied to clusters of tumors in families with
      documented germline p53 mutations, regardless of the histopathologic findings or
      pattern of tumor development.

PMID- 8302609
TI  - Should a bachelor's degree in nursing be required for OCN certification?

PMID- 8302610
TI  - Reinventing government with nursing: an urban-academic public-private
      partnership.

PMID- 8302611
TI  - Why male attendants quit nursing.

PMID- 8302612
TI  - Advanced nurse practitioner seizes opportunities.

PMID- 8302613
TI  - Take N.O.T.E.S.--a business and education partnership.

PMID- 8302614
TI  - Knowing your legal rights under the Family and Medical Leave Act.

PMID- 8302615
TI  - Advantages of insulin pumps: a personal story.

PMID- 8302616
TI  - Caring for the elderly Italian patient.

PMID- 8302617
TI  - Cort ordered support for higher education expenses--it's back.

PMID- 8302618
TI  - [Sex education from the historical and mental health viewpoint].

PMID- 8302619
TI  - [Vomiting--reflux].
AB  - Gastroesophageal reflux (GER) is a common cause of vomiting in childhood. The
      prevalence of troublesome GER disease is 5-8% in adults as well as in children.
      Many factors contribute to competency of the gastroesophageal sphincter and
      development of symptoms. In this article we describe possible mechanisms and
      clinical symptoms of gastroesophageal reflux. Methods of investigation and
      management of GER will be discussed.

PMID- 8302620
TI  - [Sports and nutrition--an ambulatory care program for obese children (long-term
      experiences)].
AB  - Sports activity (three times per week), dietary changes and modification of
      behavior are the basic tenets of an outpatient program run for 9- to 12-year-old
      adipose children since 1987. The following goals are to be attained: increase in
      physical performance capacity and body awareness, long-lasting change in eating
      habits, weight loss to less than 20% overweight compared to the age-normal, and
      understanding of the permanence of body weight problems. Individual dietary
      consultation is offered in addition to the initial examination consisting of
      physical examination, skin fat-fold measurement, blood chemical parameters,
      spiroergometry and a detailed discussion with parents and children. The eating
      habits of the children are recorded in a dietary history (three-day dietary
      protocol, questionnaire) and discussed in individual consultations with the
      parents and children. Moreover, the nutritional program includes regular
      nutritional consultations and parents' meetings every month. Cooking instructions
      provide practical knowledge of food preparation to preserve nutrients in an
      energy-reduced, tasty diet, as well as theoretical basics of nutrition. The
      control examinations show improvement in body-weight related performance capacity
      and laboratory parameters (lipid metabolism) as well as individual weight loss or
      stability (reference weight). Aware and controlled nutritional habits were
      learned especially by the children of parents who, for their part, tried to
      tailor their diets to be better balanced, whole-some and more need-oriented.
      Overall the nutritional composition improved with less energy intake. The intake
      of complex carbohydrates increased especially through consumption of ballast-rich
      musli, as well as whole wheat bread, vegetables and fruits.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8302621
TI  - [Congenital, generalized cytomegalovirus infection. Follow-up and therapeutic
      strategy with ganciclovir].
AB  - We report on a severe, generalized cytomegaly-virus-infection of a neonate with
      typical clinical symptoms and features. An attempt to treat with the antiviral
      drug Ganciclovir, an acyclic nucleoside analogue of guanine is described.

PMID- 8302623
TI  - Condoms: effective protection against HIV?

PMID- 8302622
TI  - [Intracellular measurement of anthracyclines with flow cytometry].
AB  - The intracellular drug uptake of anthracycline antibiotics, including the
      anthrachinone analogue mitoxantrone, was investigated. Measurement of drug uptake
      for each of the white cell subpopulations is possible by Flow cytometry (FCM).
      Cell separation was carried out by two different methods, using Lysing solution
      and Ficoll. Ficoll was found to be the best for further investigations in cell
      kinetics. Stock solutions of each drug, ranging from 0.5-3 micrograms/ml, were
      incubated with cell suspensions of healthy donors. In the case of doxorubicin,
      daunorubicin and epirubicin a linear correlation between drug concentration in
      the incubation medium and intracellular drug level was found. In further studies
      drug concentration was constant (1 microgram/ml or 3 micrograms/ml) and the
      intracellular drug uptake was measured at various incubation times. Examinations
      were carried out with the two different cell separation methods, mentioned above.
      In healthy donors the reproducibility of FCM measurement was examined. In
      conclusions of the results observed in experiments, FCM seems to be a suitable,
      reproducible technique for determination of cellular anthracycline concentrations
      with the exclusion of aclacinomycin A and mitoxantrone because of their physical
      properties.

PMID- 8302624
TI  - Profiles of the newly licensed nurse: historical trends and future implications.

PMID- 8302626
TI  - Transfer trauma.

PMID- 8302625
TI  - Sex and drugs and rock'n'roll.

PMID- 8302628
TI  - Pain control. No gain?

PMID- 8302627
TI  - Helpful liaisons.

PMID- 8302629
TI  - Settling David.

PMID- 8302630
TI  - Mental health: strategic thinking.

PMID- 8302631
TI  - Making sense of hip arthroscopy.

PMID- 8302632
TI  - Reflexology.

PMID- 8302633
TI  - Midwifery: mother knows best. Interview by Keren Williams.

PMID- 8302634
TI  - Whose life is it, anyway?

PMID- 8302635
TI  - Nursing abroad. Pilgrims' progress.

PMID- 8302636
TI  - Accidents: trouble in store.

PMID- 8302637
TI  - In at the deep end.

PMID- 8302638
TI  - Ageing matters. Barriers to health.

PMID- 8302639
TI  - Ageing matters. Negative perceptions.

PMID- 8302640
TI  - Joining forces.

PMID- 8302642
TI  - Global warning.

PMID- 8302641
TI  - Joint efforts.

PMID- 8302643
TI  - Fear of OH unwarranted.

PMID- 8302644
TI  - Mixed-sex wards. Mixed responses.

PMID- 8302645
TI  - Mixed-sex wards. Living together.

PMID- 8302646
TI  - Public outbreak.

PMID- 8302647
TI  - Shifting time.

PMID- 8302648
TI  - Systems of life. The ear and hearing 3.

PMID- 8302649
TI  - Visual impact. Interview by Jane Cassidy.

PMID- 8302650
TI  - A fairer deal.

PMID- 8302651
TI  - Diabetes mellitus. A significant risk.

PMID- 8302653
TI  - Students. Home truths.

PMID- 8302652
TI  - Diabetes mellitus. Test measures.

PMID- 8302654
TI  - Students. Nice work.

PMID- 8302656
TI  - Said another way. What is the language of nursing?
AB  - Nursing is multidimensional, interactive, interdisciplinary, and complex. Almost
      anything that can be said about nursing can be said another way. Some things
      worth being said and heard will not follow the norms of journal presentation. A
      forum accommodates the emerging voice, the new format, the innovative approach.
      Nursing Forum, in an effort to honor the "independent voice" in nursing, presents
      here the voice who elects to enter the dialogue, but who does so "in another
      way."

PMID- 8302655
TI  - Invest in yourself. Coping with multiple roles: mother/wife/nurse.
AB  - As we rush around attending to the essentials of our lives (family, friends,
      clients, employers), what is left? Nursing Forum invites readers to engage in
      thoughts and activities that may awaken an untouched place. We hope these
      writings will kindle your personal involvement in something that was previously
      avoided--because of bias, fear, or uneasiness--in order to stretch your mind and
      spirit.

PMID- 8302657
TI  - The index to current nursing periodical literature in the United States. L. Miles
      Raisig. 1964.

PMID- 8302658
TI  - A nurse in the family.

PMID- 8302659
TI  - Unbelievable abuse.

PMID- 8302660
TI  - When your clients are in jail.
AB  - Nursing in jails has been present for a long time and yet is still an emerging
      practice field. Often nurses are isolated in their practice arena and may be
      confused by the culture of the setting. The author examines the culture of
      correctional health care in an attempt to assist jail nurses in developing a
      framework for practice. Elements of a correctional culture are examined and
      contrasted with a nursing culture.

PMID- 8302661
TI  - Humor won, humor too: a model to incorporate humor into the healthcare setting.
AB  - The benefits of using humor in health care include stress reduction and improved
      psychological well-being for patients and the nursing staff. The authors discuss
      model to incorporate humor into a specific health-care setting, and include a
      detailed description of two humor programs: the Chuckle Wagon and Nursing Humor
      Resource Center.

PMID- 8302662
TI  - [The killer disease 'AIDS'].

PMID- 8302663
TI  - Biofeedback: a technique for controlling physiological responses.

PMID- 8302664
TI  - Handling emotions for better health: the role of a nurse.

PMID- 8302665
TI  - Caries confusion confounds.

PMID- 8302666
TI  - Intentional sealing of occlusal dentin caries: a controversial issue.

PMID- 8302667
TI  - Relationship between malocclusion and craniomandibular dysfunction in children
      and adolescents: a review.
AB  - Review of the literature on the relationship between malocclusion and
      craniomandibular dysfunction is presented. The results were interpreted by
      applying the epidemiologic approach of "necessary and sufficient," which implies
      that there must be a one-to-one relationship between a factor and a disease. If
      the correlation between malocclusion and craniomandibular dysfunction were a one
      to-one relationship, one would expect to see significant correlations reported
      consistently. Some of the studies found such significant correlations, however
      most of the correlations were weak. The lack of consistency and strength of the
      reported correlations does not support causality. On the basis of the evidence
      provided by the reviewed studies, malocclusion cannot be considered a necessary
      and/or sufficient etiologic factor of craniomandibular dysfunction. Therefore,
      early treatment of occlusal conditions to prevent the development of
      craniomandibular dysfunction is not justified scientifically.

PMID- 8302668
TI  - Association of generalized joint hypermobility with history, signs, and symptoms
      of temporomandibular joint dysfunction in children.
AB  - This study determined the prevalence of signs and symptoms of temporomandibular
      joint dysfunction (TMD) in children with and without generalized joint
      hypermobility (GJH). Twenty children with GJH, ages 4-19, and 20 age- and sex
      matched control children completed a TMD signs/symptoms history and underwent an
      examination consisting of palpation of the joints and associated musculature for
      tenderness, clicking, or crepitation. Children with historical or clinical
      findings were designated positive for TMD signs/symptoms. Maximum vertical
      opening, expressed as a percentage of lower facial height, and maximum mandibular
      lateral excursion (in mm) were recorded. Fifteen (75%) of the GJH participants
      and ten (50%) of the controls were positive for TMD findings. There were
      statistically significant differences between the groups for the presence of
      total positive findings (P < 0.001) and for responses to palpation of muscle or
      joint (P = 0.03). There were no significant differences in positive responses to
      the history alone, joint palpation alone, or muscle palpation alone. There were
      no significant differences between the groups in jaw excursions. This study
      suggests that children with GJH may be more likely to demonstrate some signs and
      symptoms of TMD than children with normal joint mobility.

PMID- 8302669
TI  - Osseointegrated dental implants as alternative therapy to bridge construction or
      orthodontics in young patients: seven years of clinical experience.
AB  - Young patients often require fixed bridgework or orthodontic therapy in cases of
      traumatic tooth loss or congenitally missing teeth. Dental implants represent an
      alternative to the more conventional treatment methods. We report positive
      experience over a seven-year period with 42 titanium Ha-Ti implants in 34
      patients aged 9 to 18 years. Fourteen implants were placed into prepared tooth
      sockets immediately after traumatic luxation of anterior teeth in 12 patients
      aged 9 to 18 years (median age 16). An additional 22 patients (median age 15.5,
      range 11 to 18) also received implants (N = 28), but these were placed only after
      healing of extraction sites, or as substitutes for congenitally missing teeth.
      Implants remained in situ for an average of 7.7 months before loading. During the
      healing period, three implants were lost due to additional trauma and one became
      infected. The 38 remaining implants osseointegrated and since have been loaded
      for five to 79 months in successful function. There was no difference between
      immediate and delayed implants in clinical success. These experiences demonstrate
      that appropriate, versatile, osseointegrated implants can provide a successful
      treatment method for young patients, without damaging adjacent teeth.

PMID- 8302670
TI  - Long-term followup of traumatized incisors treated by partial pulpotomy.
AB  - The purpose of this study was to assess the long-term success of partial
      pulpotomy in traumatized permanent incisors. Seven years before this examination,
      63 teeth that had been treated by partial pulpotomy six months to four years
      earlier were examined. At that stage, four teeth had pulp necrosis. The remaining
      59 cases were recalled for re-examination. Of these, 40 were available for
      assessment 7.5 to 11 years after the partial pulpotomy treatment. Thirty-five of
      these teeth were successful, while the remaining five had root canal fillings,
      and three of them were restored by post and crowns. Of these, two were root
      treated in consequence of new trauma, and the other two for esthetic purposes.
      The fifth tooth has probably been root treated for similar reasons, as the
      patient reported not having had any pain or problem with the tooth. The high
      frequency of long-term success justifies recommending partial pulpotomy as the
      treatment of choice for traumatic pulp exposures in crown-fractured permanent
      incisors.

PMID- 8302671
TI  - The effect of glutaraldehyde pulpotomy treatment on pulpal enzymes.
AB  - The enzymes lactate dehydrogenase (LD), succinate dehydrogenase (SD), alkaline
      phosphatase (AP), and glucose-6-phosphate dehydrogenase (G-6-PD) were evaluated
      at specific locations in pulp tissue following glutaraldehyde pulpotomies.
      Pulpotomies were performed on maxillary first molars in 40 rats after sacrifice
      at times 0, 24 hr, seven days, or one month, and experimental teeth were treated
      with 6% buffered glutaraldehyde. Teeth were prepared for frozen sectioning and
      the sections were subjected to incubation media to detect each enzyme.
      Significant differences were found regarding the location of staining and the
      time intervals at which stain was present or absent. Staining for LD and AP was
      the most intense throughout the four observation time periods, though staining
      for these enzymes as well as for G-6-PD had begun to diminish by day seven in the
      coronal thirds. Staining was completely absent in the coronal thirds at one month
      but remained in the middle and apical thirds throughout one month. SD was the
      only enzyme that was totally absent in the coronal third at seven days and
      totally absent in the middle third at one month. These findings suggest that LD,
      AP, and the biochemical mechanisms that they represent remain active longer than
      SD and G-6-PD following exposure to glutaraldehyde. This information is important
      in identifying mechanisms that are important for repair, healing, and recovery
      following pulpal injury.

PMID- 8302672
TI  - Facial electromyography and chloral hydrate in the young dental patient.
AB  - The purpose of this report is to describe facial electromyography (EMG) as a
      monitoring technique and to demonstrate the relationship of EMG amplitude to
      rated patient behavior during sedative trials using variable doses of chloral
      hydrate (CH) [25, 50, and 70 mg/kg]. Twenty healthy, uncooperative children (mean
      age = 30.7 +/- 4.8 months) participated in this institutionally approved double
      blind, repeated-measures study. Following baseline vital signs, administration of
      CH, and a 45-min period, the children were secured in a Papoose Board (Olympic
      Medical Group, Seattle, WA) with electronic monitors attached including the EMG.
      EMG amplitude was recorded continuously by computer and each visit was videotaped
      for later analysis of behavior using the Ohio State University Behavior Rating
      Scale (OSUBRS). Statistical analysis using SPSS/PC+ V2.0 (SPSS Inc., Chicago, IL)
      included descriptive statistics of the study sample, one-way ANOVA, and Pearson
      Product-Moment Correlation Coefficient to determine differences in EMG amplitude
      as a function of CH dose and associations between per cent of rated behavioral
      categories of the OSUBRS to EMG amplitude, respectively. The results indicated a
      significant difference in EMG amplitude, per cent crying and quietness as a
      function of dose (F = 3.87, P < 0.03; F = 4.64, P < 0.01; F = 3.38, P < 0.04,
      respectively). Scheffe post-hoc analysis indicated that the difference was
      between 25 and 70 mg/kg doses. Significant correlations were noted between EMG
      amplitude and per cent crying and quietness (R = 0.640, P < 0.001; R = -0.664, P
      < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302673
TI  - Temperament as a predictor of behavior for conscious sedation in dentistry.
AB  - Temperament can be defined as the behavioral style of a child or the manner in
      which a child interacts with the environment. Nine temperament categories have
      been identified: activity level, biological rhythmicity, initial
      approach/withdrawal, adaptability, intensity, mood, persistence/attention span,
      distractibility, and sensory threshold. Temperament categories can be quantified
      using the Toddler Temperament Scale (TTS), a written questionnaire completed by
      the caretaker. For this study, 29 healthy children, 14 males and 15 females, aged
      18 to 36 months (mean age 30 = 6.2 months) and a mean weight of 13.8 kg = 2.1 kg
      were sedated with 2 mg/kg hydroxyzine pamoate (p.o.) and 2 mg/kg body weight of
      meperidine (submucosal). Parents completed the TTS during dental treatment in an
      adjoining room. The recording of baseline vital statistics, the mirror and
      explorer examination, and the entire operative procedure were videotaped. The
      Ohio State University Behavior Rating Scale was used to rate the videotapes of
      each child's behavior according to the following discrete categories: quiet
      behavior, crying without struggling, and struggling movement with or without
      crying. For data analysis, all negative behavior (struggling and for crying) was
      summed. Using a stepwise linear regression, approach/withdrawal tendency
      (multiple R = 0.38, r2 = 0.15, and P = 0.0015) and adaptability (multiple R =
      0.58, r2 = 0.34, and P = 0.009) were found to predict the total percentage of
      struggling behavior, and approach/withdrawal also approached significance in
      predicting the percentage of all negative behavior (multiple R = 0.35, r2 = 0.12,
      and P = 0.055).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302674
TI  - A comparative study of pumice versus hydrogen peroxide as pretreatments for acid
      etching for resin bonding.

PMID- 8302675
TI  - Trichodentoosseous (TDO) syndrome: case report and literature review.
AB  - Trichodentoosseous (TDO) syndrome is an autosomal dominant condition
      characterized by dysplastic nails, curly hair, bone sclerosis of the long bones
      and calvarium, taurodontism, and enamel hypoplasia that occurs with
      hypomaturation/hypocalcification defects. To date, nine previous case reports of
      TDO in the dental literature have shown that while taurodontism and enamel
      defects are consistently present in TDO, the changes in the nails, hair, and
      bones may be variably expressed and occasionally not noted. Because of this, a
      few previous cases of TDO syndrome had been diagnosed simply as amelogenesis
      imperfecta. This case report highlights the typical clinical findings, diagnostic
      problems, and the clues to diagnosing this interesting condition. Clinical
      management of TDO is centered on preventing dental abscesses with stainless steel
      crowns and improving appearance with esthetic restorations.

PMID- 8302677
TI  - Comments by the American Board of Pediatric Dentistry following the External
      Review Panel's report and recommendations.

PMID- 8302676
TI  - Latex allergy in patients with spina bifida.
AB  - Latex recently has been associated with severe intraoperative IgE-mediated
      anaphylactic reactions. Pediatric patients with meningomyelocele (spina bifida)
      appear to be specifically at risk for this type of reaction. This article
      provides background information on the etiology of latex allergies, identifies
      some commonly used dental products containing latex, recommends some alternatives
      to use, and suggests precautions the dental practitioner should take when
      treating high-risk individuals such as spina bifida patients.

PMID- 8302678
TI  - Neglected pathogens: bacterial infections in persons with human immunodeficiency
      virus infection. A review of the literature (2).

PMID- 8302679
TI  - Immunomodulation with intravenous immunoglobulin.
AB  - Since its introduction over a decade ago for the treatment of primary
      immunodeficiencies, intravenous immunoglobulin (IVIG) has demonstrated activity
      in a variety of autoimmune disorders. An understanding of IVIG's immunomodulatory
      effects provides the rationale for its potential application in the management of
      autoimmune disorders. The agent has exhibited the ability to block fragment
      crystallizable receptors on phagocytes, interact with the idiotype-anti-idiotype
      network, and modulate T lymphocyte, B lymphocyte, and natural killer cell
      populations, as well as complement activity. Its immunomodulatory effects have
      been demonstrated in a variety of disorders such as idiopathic thrombocytopenic
      purpura, Guillain-Barre syndrome, Kawasaki disease. Numerous case reports and
      small studies revealed IVIG's activity in a variety of other autoimmune
      disorders, but controlled clinical trials are necessary to clarify these initial
      observations.

PMID- 8302680
TI  - The antioxidant vitamins: impact on atherosclerosis.
AB  - Atherosclerosis, the great killer of Western society, probably is initiated when
      the balance of subendothelial lipoproteins and oxidation potential is upset.
      Oxidation products, especially oxidized low-density lipoprotein, set into motion
      the cascading of numerous pathways, culminating in the fibrous atherosclerotic
      plaque. The natural antioxidant system includes enzymes and vitamins A, E, and C.
      The lipophilic vitamins A and E protect the fatty acid components of lipoproteins
      and membranes, and vitamin C functions in the aqueous phase both directly and by
      regenerating oxidized vitamin E. In animal models, the antioxidant vitamins
      protect lipids and prevent atherosclerosis. Population studies suggest an inverse
      relationship between atherosclerosis and vitamin levels. Several observational
      studies and some clinical trials have demonstrated that antioxidant vitamin
      supplements may prevent atherosclerosis. Although approximately 20% of the United
      States population regularly consumes vitamin supplements, often in high doses,
      the antiatherogenic benefits of antioxidant vitamins remain unproved by clinical
      trials, and the long-term effects of mega-dose vitamins are yet undefined.

PMID- 8302681
TI  - Prescription drugs and health care reform.

PMID- 8302683
TI  - Reassessing the therapeutic range for theophylline on laboratory report forms:
      another viewpoint.

PMID- 8302682
TI  - Reassessing the therapeutic range for theophylline on laboratory report forms:
      the importance of 5-15 micrograms/ml.
AB  - The therapeutic status of theophylline has changed dramatically over the last
      decade. As part of this change, a different view of the most appropriate
      therapeutic range for serum theophylline concentration (STC) has emerged. The
      National Institutes of Health Expert Panel Report, "Guidelines for the Diagnosis
      and Management of Asthma," suggests a conservative approach of aiming for STC of
      5-15 micrograms/ml. This truly landmark document along with several studies in
      the literature, recently prompted us to change our hospital's laboratory report
      form for the medical record to read that the therapeutic range for STC is 5-15
      micrograms/ml. We encourage hospital laboratories or other clinical laboratories
      who have not already made this change to do so.

PMID- 8302684
TI  - Reassessing the therapeutic range for theophylline: another perspective.

PMID- 8302685
TI  - Trimethoprim-sulfamethoxazole pharmacokinetics in trauma patients.
AB  - STUDY OBJECTIVES: To characterize the pharmacokinetic profile of trimethoprim
      sulfamethoxazole (TMP-SMX) in trauma patients and to compare these parameter
      estimates with those obtained in nontrauma patients. DESIGN: Open-label,
      multidose, pharmacokinetic study. SETTING: Trauma intensive care unit of a level
      1 trauma center located within a regional medical center. PATIENTS: Fifteen adult
      trauma patients with serious gram-negative infections. All patients were studied
      on day 1 of treatment, nine on day 3, three on day 5, and two on day 7. One
      patient was discontinued from the study because of a possible drug-induced rash.
      INTERVENTIONS: Study patients received TMP 4 mg/kg and SMX 20 mg/kg intravenously
      every 12 hours. Serial blood sampling was performed up to 4 times per patient
      between treatment days 1 and 7. Serum was assayed for TMP-SMX using high
      performance liquid chromatography. A one-compartment model was fit to the data
      using maximum likelihood estimation. MEASUREMENTS AND MAIN RESULTS: Mean (SD)
      baseline parameter estimates for TMP were volume 2.1 (0.65) L/kg, half-life 9.7
      (3.0) hours, and clearance 2.6 (0.80) ml/min/kg. Estimates for SMX were volume
      0.51 (0.10) L/kg, half-life 7.8 (2.0) hours, and clearance 0.80 (0.29) ml/min/kg.
      Both volume (p < 0.01) and clearance (p < 0.001) for SMX were significantly
      higher and half-life (p < 0.05) significantly shorter than previously reported
      estimates in nontrauma patients. No significant differences in TMP parameter
      estimates were found. Neither TMP nor SMX clearance was significantly correlated
      with estimated creatinine clearance (p > 0.05). CONCLUSION: The results indicate
      that the pharmacokinetics of SMX in trauma patients differ significantly from
      nontrauma patients, which may result in lower than expected concentrations using
      standard dosing guidelines.

PMID- 8302686
TI  - Comparison of the pharmacokinetic and pharmacodynamic activity of piperacillin
      and mezlocillin.
AB  - STUDY OBJECTIVE: To compare serum bactericidal activity over time and
      pharmacokinetics resulting from single doses of piperacillin (PIP) and a single
      dose of mezlocillin (MEZ). DESIGN: Open-label, randomized, three-way crossover
      study. SETTING: Hartford Hospital Clinical Research Center. PATIENTS: Nine
      healthy volunteers. INTERVENTIONS: Subjects received single doses of PIP 3 and 4
      g/70 kg, and a single dose of MEZ 5 g/70 kg. MEASUREMENTS AND MAIN RESULTS: Test
      organisms were two clinical isolates of Pseudomonas aeruginosa. Pharmacodynamic
      analysis revealed that PIP 4 g had 2- to 3-fold higher peak serum bactericidal
      activity at the end of infusion and 4- to 5-fold higher activity at 0.5 hour than
      did MEZ 5 g, and also provided approximately 1 hour additional activity over MEZ
      5 g. Pharmacokinetic analysis revealed that serum concentrations resulting from
      PIP 4 g remained above the minimum inhibitory concentration of our test strains
      almost twice as long as MEZ 5 g. CONCLUSION: Since mezlocillin 5 g every 8 hours
      is currently proving to be effective at many institutions, and since piperacillin
      4 g demonstrates superior pharmacokinetic and pharmacodynamic activity, we
      believe that piperacillin 4 g every 8 hours could be used instead, with resulting
      cost savings.

PMID- 8302687
TI  - Bioequivalence of soft gelatin capsules and oral solution of a new cyclosporine
      formulation.
AB  - STUDY OBJECTIVE: To compare the bioavailability of cyclosporine from two oral
      dosage forms of a new microemulsion formulation. DESIGN: Open, randomized, three
      treatment, three-period crossover investigation. SETTING: University-affiliated
      clinical pharmacology research unit. PATIENTS: Twenty-four healthy male
      volunteers. INTERVENTIONS: Single oral administrations of cyclosporine 180 mg
      given as a soft gelatin capsule (reference), an oral solution under fasting
      conditions, and the oral solution mixed with orange juice. MEASUREMENTS AND MAIN
      RESULTS: Serial venous blood samples were obtained over 48 hours after each
      administration to measure cyclosporine in whole blood by a specific monoclonal
      radioimmunoassay. For all three treatments, the mean maximum blood concentration
      (Cmax) of approximately 1100 ng/ml was reached at about 1.3 hours (tmax) after
      administration; the area under the blood concentration-time curve (AUC) was, on
      average, 4700 ng.hr/ml. Bioequivalence was conclusively demonstrated for both the
      absorption rate (Cmax and tmax) and extent (AUC) of cyclosporine among the
      treatments inasmuch as the point estimates and 90% confidence intervals were
      within the respective equivalence ranges. CONCLUSIONS: When administered in
      conjunction with routine concentration monitoring, the two oral dosage forms of
      the new microemulsion formulation of cyclosporine can be interchanged without
      need for dosage adjustments. In addition, the oral solution can be mixed with
      fruit juice without affecting the rate or extent of cyclosporine absorption.

PMID- 8302688
TI  - Ambulatory pharmacy services affiliated with acute care hospitals.
AB  - The extent to which hospital-based pharmacists provide ambulatory clinical
      pharmacy services in the United States is unknown. We evaluated pharmacists'
      activities in hospital-affiliated ambulatory clinics and home health services. A
      questionnaire was mailed to directors of pharmacy in one-half of the United
      States acute care general medical-surgical hospitals with 50 or more licensed
      beds. The survey response rate was 56% (n = 1174). In 19% of hospitals,
      pharmacists provided patient care (nondispensing activities) in ambulatory
      clinics. The most common clinics with pharmacist involvement were diabetes (10%
      of hospitals), oncology (9%), cardiology (6%), and geriatrics, infectious
      disease, and pain (4% each). Nondispensing roles varied by clinic type;
      prescribing by protocol was performed in 57% of anticoagulation clinics and 7% of
      diabetes clinics. Home health care services, with pharmacists' activity extending
      beyond providing drugs, were offered by 28% of the hospitals. Thirty-six percent
      of the hospitals operated one or more outpatient pharmacies. A statistically
      significant association was observed between hospitals' inpatient clinical
      pharmacy services (as assessed by the pharmaceutical care index) and the
      involvement of pharmacists in both ambulatory clinics and home health care
      services.

PMID- 8302689
TI  - Pharmacotherapy of infectious complications in patients with acquired
      immunodeficiency syndrome.

PMID- 8302690
TI  - Mycobacterial infections.
AB  - Infection due to Mycobacterium tuberculosis continues to plague humanity. In the
      United States, conditions have taken a decided turn for the worse, with an
      increasing frequency of infection and the spread of multiple-drug-resistant
      strains. A number of strategies are available to improve the management of this
      epidemic. Mycobacterium avium is now recognized as a significant cause of
      morbidity and mortality in patients with the acquired immunodeficiency syndrome.
      Therapy is limited due to relative drug resistance, drug intolerance, and drug
      malabsorption; however, potentially useful regimens are being developed.

PMID- 8302691
TI  - Pneumocystis carinii pneumonia in human immunodeficiency virus-infected infants
      and children.
AB  - Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection
      in adults and children infected with the human immunodeficiency virus (HIV).
      Without prophylaxis, half of all these children will develop PCP at sometime
      during their illness. The disease is associated with high mortality and a poor
      prognosis for long-term survival in this patient population. In infants and young
      children, PCP may be a primary infection, compared with reactivation of a latent
      infection that is usually the case in older children and adults. Clinical
      features, radiographic findings and diagnostic strategies are similar in children
      and adults. Although alternative agents are being investigated,
      trimethoprimsulfamethoxazole (TMP-SMX) and pentamidine remain the standard
      therapeutic agents. Insufficient data are available to recommend routine
      adjunctive corticosteroids in children with acquired immunodeficiency syndrome
      (AIDS), PCP, and significant respiratory disease. Prophylaxis against PCP
      occurrence or recurrence is indicated for HIV-infected children and infants under
      1 year of age, children with less than 20% T4 helper lymphocytes, those meeting
      age-related Centers for Disease Control (CDC) guidelines for prophylaxis, and
      those with a history of suspected or documented PCP. The CDC recommends
      intermittent TMP-SMX for PCP prophylaxis in children with AIDS.

PMID- 8302692
TI  - Anaphylactoid reaction with suramin.
AB  - Suramin, a drug used to treat parasitic diseases, is currently being investigated
      as a treatment for metastatic prostate cancer. A 73-year-old man had an
      anaphylactoid reaction following the first dose of suramin. It was treated
      successfully with epinephrine, diphenhydramine, and hydrocortisone. Investigators
      should be aware of the possibility of such a reaction with parenteral
      administration of this drug.

PMID- 8302693
TI  - Eight days of cyclosporine overdose: a case report.
AB  - A 25-year-old woman was admitted to the hospital because of rising trough
      cyclosporine concentrations thought to be due to self-administration of 4 times
      the normal dosage of the drug for 8 days. Her symptoms included colicky central
      abdominal pains and urinary retention; her serum creatinine concentrations were
      elevated. Whole blood cyclosporine and metabolite concentrations were measured by
      high-performance liquid chromatography and monoclonal radioimmunoassays. The
      highest reported trough cyclosporine concentration was 5877 ng/ml, and AM1 (M17)
      concentration was 3425 ng/ml. A cyclosporine half-life of 91 hours was
      calculated. Nine days after the agent was discontinued the patient's serum
      creatinine concentration had returned to normal and her symptoms resolved. Due to
      the availability of three sizes of cyclosporine capsules, and the need for
      frequent dosage changes, continued vigilance is necessary to ensure that patients
      understand their drug regimen.

PMID- 8302694
TI  - Template for the evaluation of a clinical pharmacist. American College of
      Clinical Pharmacy.
AB  - Pharmacists are expected to deliver pharmaceutical care, that is, to accept
      responsibility for patients' well-being by ensuring optimum outcomes of drug
      therapy. Therefore, their performance must be evaluated based on this
      expectation. The template should be a useful tool for assessing the extent to
      which clinical pharmacists' performance meets predefined practice standards. Its
      adaptability will allow it to meet site- and pharmacist-specific requirements for
      performance appraisal. The evaluator and clinical pharmacist should work together
      to establish a priori percentage standards.

PMID- 8302695
TI  - Evaluating the performance of clinical pharmacy faculty: putting the ACCP
      template to use.
AB  - The responsibilities of clinical faculty members are often multifaceted and may
      include direct patient care, didactic and experiential teaching, research, and
      administrative duties. Specialization, poorly defined standards of care, and lack
      of direct supervision have traditionally made performance evaluation difficult.
      We implemented a method to evaluate clinical faculty as they carried out patient
      care activities using a revised template for the evaluation of a clinical
      pharmacist developed by the American College of Clinical Pharmacy Clinical
      Practice Affairs Committee. In addition, it allows individuals to report and
      evaluate their own performance in the areas of patient care, instructional
      activity, university and public service, research and scholarly activities, and
      administrative duties. Teaching evaluations from clerkship students and residents
      are also submitted and assessed during the annual interview. To determine the
      usefulness of the evaluation, including the template, we surveyed the opinions of
      clinical faculty (nontenured) at four primary practice sites (response rate 92%).
      Mean scores for responses suggested agreement with statements as to the merits of
      the evaluation system; however, there was some variation among practice sites.
      Incorporating the template into a broad evaluation system was effective in
      facilitating improved job performance and career development. Adaptation of the
      template may be practice site dependent and should be coordinated by a
      participative approach. Additional assessment may be facilitated by physician,
      nurse, or peer evaluation.

PMID- 8302696
TI  - Emergency medical services preparedness for pediatric emergencies.
AB  - The study objective was to examine emergency medical services (EMS) equipment and
      training preparedness for pediatric emergencies in Oklahoma. The participants
      were 202 administrators of licensed EMS agencies in the state of Oklahoma. A
      mailed questionnaire was used to obtain data from EMS agencies regarding
      emergency ambulance run characteristics, medical control, equipment, and
      personnel training. There were 130 questionnaires returned (response rate, 64%).
      Overall, 4% of EMS emergency runs were for children under 12 years. Family
      medicine and emergency medicine were the most frequent specialties of medical
      directors. Fewer services allow personnel to perform endotracheal intubation on
      children (35 services) than on adults (45 services). Fewer services allow
      personnel to start intravenous lines on children (40 services) than on adults (47
      services). Equipment for pediatric care routinely stocked on ambulances was
      tabulated. Most services provided intraagency continuing education, but only 71
      (54%) included pediatric topics in continuing education. Deficiencies in
      equipment and training for pediatric emergencies are a common problem for EMS
      agencies in Oklahoma. Barriers to preparedness include: 1) relative infrequency
      of pediatric runs and difficulty with maintenance of technical skills, 2) costs
      associated with increased equipment and training, and 3) hesitancy to allow
      personnel to perform advanced life support procedures on children.

PMID- 8302697
TI  - Pulmonary edema associated with upper airway obstruction in dogs.
AB  - In order to evaluate the effect of acute upper airway obstruction upon pulmonary
      edema (PE) formation, we studied seven dogs that were subjected to inspiratory
      obstruction for three hours. Hypoxia was avoided by the administration of
      supplemental oxygen during the study period. Six dogs developed pulmonary
      vascular congestion, and four developed histologic findings of PE. Inspiratory
      intrapleural pressure decreased to -28 +/- 4 mmHg in dogs that developed PE and
      to -23 +/- 2 mmHg in dogs that did not. Transmural pulmonary artery pressure and
      pulmonary artery wedge pressure did not increase significantly. Central venous
      pressure during inspiration (CVPi) increased in all dogs, and CVP at end
      expiration (CVPe) was significantly higher in dogs with PE. Dogs that developed
      PE experienced a decrease in cardiac output and an increase in systemic vascular
      resistance. Furthermore, alveolar ventilation declined in dogs with PE,
      ultimately resulting in ventilatory failure. Pulmonary edema formation was not
      preceded by an increase in pulmonary vascular pressures but was associated with
      higher CVP, pulmonary vascular congestion, and hypercarbia.

PMID- 8302698
TI  - A two-year retrospective study of accidental pediatric albuterol ingestions.
AB  - A two-year retrospective review of accidental albuterol ingestions in children
      less than 12 years old was performed to assess overdose toxicity and to
      investigate a dose-effect relationship. One hundred twelve exposures were
      located. Seventeen cases were excluded owing to coingestants, leaving 95 cases
      for evaluation. Twenty-nine children (30%) remained at home without intervention
      or telephone followup because of an ingestion of less than 0.6 mg/kg. Twenty
      eight patients (30%) were followed at home by telephone (12 of whom received
      ipecac). Dosages ranged from 1 to 27 mg, with dose/weight ratios of 0.1 to 1.9
      mg/kg. Two children experienced transient mild symptoms (irritability, brief
      nausea, and vomiting). The remaining 26 children were asymptomatic. Thirty eight
      cases (40%) were treated in an emergency department. Ingestions ranged from 2 to
      96 mg, with dose/weight ratios of 0.3 to 6.3 mg/kg. Ages ranged from one to 11
      years. Transient restlessness or irritability was observed in 16 patients,
      tachycardia in 15, tremors in six, and a widened pulse pressure in one. No
      serious events occurred in this series, and no patient required treatment beyond
      gastrointestinal decontamination. For ingestions of 0.6 mg/kg or less, treatment
      at home with observation may be sufficient. For larger ingestions, eg, greater
      than 0.6 mg/kg, consideration should be given to direct medical evaluation and
      gastrointestinal decontamination.

PMID- 8302699
TI  - Vaginal discharge as an indicator of gonorrhea and Chlamydia infection in girls
      under 12 years old.
AB  - Cultures for sexually transmitted diseases (STDs) are frequently obtained as part
      of an evaluation for alleged sexual abuse, but the prevalence of STDs in abused
      children is very low. Furthermore, STDs in children may not be identified if the
      clinician does not maintain a high index of suspicion in the symptomatic child. A
      retrospective review was done to study the symptoms and presenting complaints of
      girls under 12 with gonorrhea and chlamydia infections and to examine the
      prevalence of STDs in asymptomatic girls. The charts of 622 patients were
      reviewed. All patients were females under 12, Tanner I or II, who were initially
      seen for evaluation of sexual abuse or who were diagnosed with an STD. During the
      study period, 28 girls were found to have STDs. Twenty-two of these girls had
      vaginal gonorrhea; vaginal chlamydia was diagnosed in eight. Twenty-three of the
      28 girls (82%) with an STD were initially seen and cultured for a chief complaint
      of vaginal discharge. Of the 581 patients who were cultured for evaluation of
      abuse, only five STDs were diagnosed (0.7%). All 22 girls with gonorrhea had a
      vaginal discharge on examination. Of the eight girls with chlamydia, two also had
      vaginal gonorrhea. Of the six who had chlamydia without gonorrhea, asymptomatic
      infection was common; four gave histories of discharge but only one had a
      discharge on examination. Our review indicates that girls under 12 who present
      for evaluation of vaginal discharge may have an STD and should be cultured for
      gonorrhea and chlamydia whether or not sexual abuse is suspected.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8302701
TI  - Scrotal masses in children and adolescents: a review for the emergency physician.

PMID- 8302700
TI  - Empiric therapy of perianal lesions in a sexually abused child: medical and
      forensic implications.
AB  - A two-year, eight-month-old boy was diagnosed clinically with perianal warts and
      treated with topical 5-Fluorouracil, with subsequent resolution of the lesions.
      The child disclosed sexual abuse, and subsequent physical abuse was also
      documented. Attempts to identify the perpetrator have been hampered by the
      child's young age and resolution of the skin lesions. The forensic implications
      of this case are discussed.

PMID- 8302702
TI  - Glucose analyzers.

PMID- 8302703
TI  - Baby not breathing.

PMID- 8302704
TI  - Flu-like symptoms in a child.

PMID- 8302705
TI  - Case 05-1993: a sleepy child from same-day surgery.

PMID- 8302706
TI  - Proliferation, basement membrane changes, metastasis and vascularization patterns
      in human breast cancer.
AB  - Tumour cell proliferation shows a heterogeneous intratumour distribution. By
      comparison with the infiltrating component of breast cancers, the intraductal
      component has a significantly lower proliferation index. The cells at the
      periphery of infiltrating tumour strands have a higher proliferation activity
      than the cells in the core. A variable turn-over of basement membrane material is
      reported in infiltrating cancers. Increased amounts of type IV collagen are
      demonstrated in areas of periductal elastosis and of interstitial elastosis in
      breast cancer. Important parallels are found between metastatic tumour cells and
      the macrophages acting in the process of inflammation. We found evidence that
      displacements of tumour cells and macrophages are similar. Studies of
      vascularization in transplanted tumours cannot be extrapolated to man. A striking
      heterogeneity in the organization of vessels and in the expression of some
      markers is observed in human breast cancer.

PMID- 8302707
TI  - Immunohistochemical determination of estrogen and progesterone receptor content
      in human breast cancer. Computer-assisted image analysis (QIC score) vs.
      subjective grading (IRS).
AB  - Immunohistochemistry of Estrogen Receptor (ER) and Progesterone Receptor (PR) has
      been performed in 687 cases of human breast cancer. The staining results have
      been compared by (1) computer-assisted image analysis (QIC Score) and (2)
      subjective grading of the cryostat sections ("German" IRS). Tumors without or
      with only weak ER or PR content may be distinguished by both methods from tumors
      with a high receptor content. The QIC Score values belonging to the intermediate
      IRS grades are distributed over a wide range, but no negative cases were found in
      these categories. It is concluded from our results that subjective grading of the
      slides is a simple, rapid and useful method for the determination of the tissue
      receptor content and must not be replaced by the expensive and time-consuming
      computer-assisted image analysis in daily practice.

PMID- 8302708
TI  - Immunohistologic analysis of invasive phenotype in breast carcinoma. A
      clinicopathologic study.
AB  - Acetone-fixed, cryostat sections of 81 snap-frozen invasive breast carcinomas
      were immunostained with monoclonal antibodies to Cathepsin D (CD), a protease
      believed to mediate extracellular matrix dissolution, and Type IV collagen, a
      constituent of basal lamina (BL). Most cases (48/81, 53%) exhibited focal, patchy
      BL distribution (1+) around tumor cell nests, although subsets with diffuse
      continuous (2+) peritumoral sheets (15/81, 19%) or near complete absence (0+,
      23/81, 28%) were also observed. Elaboration of BL was correlated with favorable
      morphologic differentiation (0+ BL-57% poorly differentiated vs. 2+ BL-13% poorly
      differentiated, p = .01), absence of nodal or systemic metastases (0+ BL-78%
      metastatic vs. 2+ BL-40% metastatic, p = .02), and improved disease-free survival
      (0+ BL-63% recurred vs. 2+ BL-20% recurred, p = .05). In addition, neoplastic
      cells expressed CD more frequently in tumors which lacked detectable BL synthesis
      (0+ BL-91% CD+ vs. 2+ BL-57% CD+, p = .03). The observed relationships between
      morphologic growth pattern, BL synthesis and CD expression imply conventional
      grading in large parts reflects activity or extent of host tissue invasion by a
      given neoplasm. Widespread but heterogeneous distribution of BL in breast tumors
      also suggests partial equilibrium between neoplastic and host tissues in most
      cases.

PMID- 8302709
TI  - Mucinous lesions of the breast. A pathological continuum.
AB  - Mucocele-like tumor and invasive mucinous carcinoma of the breast may represent
      the two ends of the pathological spectrum of mucinous lesions of the breast,
      respectively. Little data exists on mucinous lesions that may be considered
      intermediate between mucocele-like tumor and invasive mucinous carcinoma. We
      studied 23 consecutive cases of invasive mucinous carcinoma of the breast and
      observed the following associated intermediate mucinous lesions: mucin-filled
      ducts (MFD) with unremarkable epithelium in 15 cases (65%), MFD with typical
      ductal hyperplasia in 9 cases (39%), MFD with atypical ductal hyperplasia in 5
      cases (22%), and MFD with intraductal carcinoma in 13 cases (57%; micropapillary
      or cribriform types). Eighteen cases (78%) contained MFD with one of these four
      lesions and five cases (22%) contained all four lesions. Twenty-three consecutive
      cases of infiltrating ductal carcinoma-not otherwise specified (IDC-NOS), 21
      cases of intraductal carcinoma, and 50 consecutive cases of surgically-excised
      breast tissue with fibrocystic change (FC), were similarly reviewed. Only one
      case (4%) of IDC-NOS, 1 case of intraductal carcinoma, and two cases (4%) of FC,
      contained small foci of MFD with intraductal carcinoma, intraductal carcinoma,
      and unremarkable epithelium, respectively. Our findings suggest the presence of a
      spectrum of mucinous lesions of the breast which represents a pathological
      continuum.

PMID- 8302710
TI  - The prognostic significance of AgNOR counts in lymph node deposits of breast
      carcinomas.
AB  - Low AgNOR counts in metastatic lymph node deposits confer a longer 5-year
      survival rate in patients with breast carcinoma compared with those having high
      AgNOR counts. This was demonstrated in a series of 30 axillary lymph nodes from
      an equal number of patients with malignant breast disease. The beneficial effect
      of the low AgNOR status was independent of tumour differentiation, tumour size
      and the patients' age using univariate analysis, but it was related to the number
      of lymph nodes with metastatic disease. It is thought that AgNOR counts in
      axillary lymph node metastases may be an additional prognostic variable in
      assessing breast tumour behaviour.

PMID- 8302711
TI  - Modification of standard proteinase K/phenol method for extraction of DNA from
      small tumour biopsies.
AB  - The standard proteinase K/phenol DNA isolation method was found to produce
      unsatisfactory yields of DNA from small tissue biopsies (less than 50 mg). The
      influences of the volume of cell lysis buffer and the amount of proteinase K on
      the final DNA yield and quality were studied, and an improved method was devised
      and compared with both the standard procedure and a phenol-free protocol. The
      optimal volume of cell lysis buffer was found to be 200 microliters per mg of
      tissue while the optimal amount of proteinase K was 60 micrograms per mg of
      tissue. A mean yield of 12 mu/mg tissue of pure, high molecular weight DNA was
      achieved from 50 frozen samples prepared by crushing. Yields from 20 microns
      thick cryostat sections reached 30 micrograms/mg.

PMID- 8302712
TI  - Extracerebral toxoplasmosis in the acquired immunodeficiency syndrome (AIDS).
AB  - Although Toxoplasma gondii frequently causes lesions of the central nervous
      system in AIDS, the exact incidence of extracerebral toxoplasmosis in these
      immunodepressed patients remains difficult to determine. Isolation of the
      parasite outside the central nervous system is rarely performed ante mortem, and
      most diagnoses of extracerebral toxoplasmosis are made post mortem. This article
      describes 23 cases of extracerebral toxoplasmosis diagnosed between 1987 and 1991
      in an autopsy series of 170 patients infected with the human immunodeficiency
      virus (HIV). Ante mortem diagnosis of extracerebral involvement was affirmed in 4
      of these 23 patients by identification of trophozoites in bronchoalveolar lavage
      fluid (2 cases), a surgical pulmonary biopsy specimen, and a bladder biopsy.
      Clinical and paraclinical findings suggested cardiac involvement in 4 other
      patients. Post mortem examination demonstrated disseminated toxoplasmosis in 18
      cases and extracerebral monovisceral involvement in 5 cases. Extracerebral
      toxoplasmosis was directly responsible for the death of 6 patients. The most
      frequent extracerebral sites of Toxoplasma gondii involvement were the heart
      (21/23 cases; 91%), the lungs (14/23 cases; 61%) and the pancreas (6/23 cases;
      26%). The tissular consequences of toxoplasmic involvement varied considerably,
      from formation of pseudocysts or cysts without any surrounding inflammatory
      reaction to necrotic lesions rich in neutrophilic polynuclear cells containing
      numerous free parasites. Immunoperoxidase study using antitoxoplasmic antibodies
      contributed to the diagnosis of 8 extracerebral localizations. Electron
      microscopy examination of a surgical lung biopsy and myocardial specimens (2
      cases) demonstrated the ultrastructural characteristics of Toxoplasma gondii
      trophozoites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302713
TI  - Motor neuron disease/amyotrophic lateral sclerosis--lessons from ubiquitin.
AB  - Ubiquitin is a stress protein implicated in the degradation of short-lived and
      abnormal proteins. In a neuropathological study of 43 cases with motor neuron
      disease/amyotrophic lateral sclerosis (MND/ALS) and 44 control cases the
      distribution and specificity of Bunina bodies and ubiquitin-reactive inclusions
      (UBRI) were investigated. The primary motor area showed nerve cell loss in 67%,
      Bunina bodies in Betz cells (10%) and UBRI in small pyramidal cells (17%).
      Degeneration of anterior horn cells in all cases coincided with Bunina bodies
      (84%) and UBRI (98%) in the same location; the motor nuclei of the caudal brain
      stem were also involved almost to the same degree. More resistant nuclei like the
      oculomotor nuclei or the Onuf's nucleus showed no degeneration but UBRI in 11%
      and 18% of cases, respectively. Like the degenerative process, the formation of
      UBRI was not confined to motor nuclei but also involved the brain stem reticular
      formation, substantia nigra, and Clarke's nucleus showing that MND/ALS is a
      multiple system degeneration. UBRI were found in only one control case in the
      anterior horn cells and in one case in the hypoglossal nucleus showing that UBRI,
      although not being absolutely specific for MND/ALS, have practical value for the
      neuropathological diagnosis of that disease. The pathogenetical implications of
      UBRI in MND/ALS are discussed.

PMID- 8302714
TI  - Common acute lymphoblastic leukemia antigen expression on visceral epithelial
      cells in several types of glomerulonephritis.
AB  - The distribution of a group of glomerular antigens and the composition of
      deposits was examined by immunoelectron microscopy in patients with idiopathic
      membranous nephropathy (MN), focal segmental glomerulosclerosis (FSG) and
      membranoproliferative glomerulonephritis (MPGN). The decrease in expression of
      common acute lymphoblastic leukemia antigen (CALLA) on glomerular visceral
      epithelial cells was found in MN and FSG. The loss of CALLA on visceral
      epithelial cells was typical for immature glomerulus and for this cell culture.
      On the strength of these results we can suppose that the dedifferentiation of
      visceral epithelial cells takes place in MN and FSG. It leads to changes in the
      synthesis of the glomerular basement membrane components.

PMID- 8302715
TI  - Primary mucinous carcinoma of the renal pelvis.
AB  - A case of primary mucinous carcinoma originating in the renal pelvis associated
      with renal lithiasis is reported. The left kidney removed was mostly occupied by
      mucinous carcinoma with areas of signet ring cell carcinoma. The epithelium
      covering the pelvis consisted of a single layer of columnar epithelium with
      scattered goblet cells and mucous glands. A series of careful examinations of the
      abdominal viscera failed to disclose any other primary lesion. The patient died
      with multiple peritoneal tumor disseminations eight months after the operation
      despite additional chemotherapy.

PMID- 8302716
TI  - Mixed renal tumor with carcinomatous and fibroleiomyomatous components,
      associated with angiomyolipoma in the same kidney.
AB  - A 54-year-old woman, without the stigmas of tuberous sclerosis, underwent radical
      nephrectomy for simultaneous occurrence of an Angiomyolipoma (AML) and a
      carcinomatous and fibroleiomyomatous mixed tumor in the same kidney, diagnosed by
      computerized tomography, selective renal arteriography and anatomopathological
      examination. The peculiar findings of the mixed neoplasia, characterized by a
      mixture of carcinomatous and fibroleiomuscular components are stressed. The
      latter component is considered to be a proliferative element interacting with the
      carcinomatous one. After review of the pertinent literature, this is the first
      example of an association of AML and renal cell carcinoma (RCC) in which the RCC
      is constituted by a mixture of carcinomatous and fibroleiomyomatous cells.

PMID- 8302717
TI  - Polycystic tumor of the atrioventricular nodal region in a man with Emery
      Dreifuss muscular dystrophy.
AB  - Benign polycystic tumor of the atrioventricular nodal region is a lesion
      associated with cardiac conduction defects with atrioventricular block and sudden
      death. We present the clinical and light microscopical, immunohistochemical and
      ultrastructural findings of such a lesion in a young man with X-linked recessive
      Emery-Dreifuss muscular dystrophy who died suddenly. The tumor has not previously
      been described in this group of patients, who frequently suffers from cardiac
      electric instability and sudden death. Possible mechanisms by which the tumor may
      cause arrhythmia are discussed and the presence of neuroendocrine cells in the
      lesion is emphasized.

PMID- 8302718
TI  - Multiple primary tumours.

PMID- 8302719
TI  - Reproducibility of subjective immunohistochemical estrogen- and progesterone
      receptor determination in human endometrium.
AB  - To obtain a reliable scoring system for semi-quantitation of estrogen- (ER) and
      progesterone receptors (PgR) in human endometrial tissue, we investigated the
      reproducibility of subjective immunohistochemical ER and PgR determination.
      Specimens of frozen endometrial tissue were stained once (n = 129) or twice (n =
      22) using the ER-ICA and PgR-ICA kits from Abbott. The semi-quantitative approach
      we used included subjective estimates of the overall staining intensity (I) and
      of the fraction of stained cells (%). Scoring was performed twice by the same
      observer and once by another observer (n = 87). Intra- and inter-observer
      agreement were evaluated using Kappa statistics. We found that more comprehensive
      scorings of I and % could not be agreed upon by the observers. Only simplified
      estimates of the fraction of cells stained and overall staining intensity were
      reproducible. Subjective estimates obtained by this method agreed with estimates
      obtained by counting (n = 38). Simplified H-scores, which were obtained by
      multiplication of the simplified estimates of % and I, were reproducible, too. In
      addition, semi-quantitation of ER and PgR by immunohistology was significantly
      correlated to quantitation by enzyme-immunoassay (n = 39). Thus, it was possible
      to reproducibly semi-quantitate ER and PgR only by employing a very simple
      immunohistochemical scoring of ER and PgR.

PMID- 8302720
TI  - Multicentric papillomavirus infection of the female genital tract. A study of
      morphologic pattern, possible risk factors and viral prevalence.
AB  - We have investigated 103 biopsy specimens obtained from 50 women (average 28.1
      years, range 16-66) with multicentric condylomatosis of the genital tract,
      including the uterine cervix (48 samples), the vagina (23), and the vulva (32).
      Each patient had at least 2 biopsies. A positive in situ hybridization for a
      Human Papilloma Virus (HPV) cocktail was observed in samples from 38 patients: in
      these multiplicity of lesions regarded the cervix and vulva (22 cases), cervix
      and vagina (12), vulva and vagina (1), cervix, vulva and vagina (3). Viral types
      6,11 were more prevalent in simple condylomata. Both low- and high grade lesions
      of cervix, vagina, and vulva showed prevalence of types 16, 18 and 31, 33, 35.
      Signaling for more than one probe cocktail was detected in 14 (13.6%) samples.
      Partner's condylomatosis was referred to by a sizeable minority of patients. It
      is concluded that the spectrum of HPV infection in the female genital tract
      reflects a multiplicity of factors, including involved viral type and site,
      immunitary reaction of the host, perpetration or reactivation of latent
      infections.

PMID- 8302721
TI  - Nucleolar organizer regions in myofibroblasts in breast cancer. Relation to
      cancer cell morphometry, flow cytometry, sex steroid receptor content, tumour
      histology and prognosis.
AB  - The number of silver-stained nucleolar organizer regions (Ag-NORs) was counted in
      stromal myofibroblasts in 125 cases of breast cancer. The mean (S.E.) of Ag-NORs
      in stromal myofibroblasts was 4.4 (0.1). The number of Ag-NORs in myofibroblasts
      was related to histological grade (p = 0.028), histological type (p = 0.013),
      tumour necrosis (p = 0.026), mitotic frequency (p = 0.091) and S-phase fraction
      (p = 0.032). The number of Ag-NORs in stromal myofibroblasts predicted survival
      with a borderline significance (x2 = 3.4, p = 0.052) and also in axillary lymph
      node negative tumours (X2 = 2.8, p = 0.095). The recurrence-free survival in the
      entire cohort (X2 = 7.1, p = 0.0075) and in axillary lymph node negative tumours
      (X2 = 7.1, p = 0.0078) could be predicted on the basis of the number of Ag-NORs
      in stromal myofibroblasts. In axillary lymph node positive tumours the number of
      Ag-NORs in stromal myofibroblasts had no prognostic value. In multivariate
      analysis the number of Ag-NORs in stromal myofibroblasts had no independent
      prognostic value. The results suggest a close interaction between stromal
      myofibroblasts and epithelial cancer cells in breast cancer, and stromal changes
      are clearly a subject for further analyses.

PMID- 8302722
TI  - Immunohistochemical detection of S-100, S-100 alpha, S-100 beta proteins, glial
      fibrillary acidic protein, and neuron specific enolase in the prenatal and adult
      human salivary glands.
AB  - Developing human fetal salivary glands of gestational age from 10 to 40 weeks (n
      = 100) and normal adult glands (n = 10) were examined for immunoreactivity to S
      100 protein and its subunits S-100 alpha, S-100 beta, glial fibrillary acidic
      protein (GFAP) and neuron specific enolase (NSE). In the early intermediate
      developmental stage (19-32 weeks) some acinar basal cells showed immunoreactivity
      to S-100 protein which rapidly disappeared in the late developmental stage (33-40
      weeks). Adult salivary glands were negative for S-100 protein. The S-100 alpha
      subunit was strongly positive in the glandular ducts and acini of both fetal and
      adult glands. The S-100 beta, although present in some acini and ductal cells
      during the late intermediate developmental stage, was rarely seen in the adult
      glands. GFAP and NSE was positive at the developing salivary epithelium in the
      early developmental stage (15-18 weeks). The above findings indicated that the
      developing salivary epithelia showed transient appearance of the neuronal
      phenotype during active cytodifferentiation stage of glandular acini and ducts.
      Therefore, after evaluation of normal developmental and neoplastic transformation
      of the salivary glands a suggestion that neuronal differentiation of ductal
      reserve cells is responsible for the production of modified myoepithelial cells
      in both normal developmental salivary gland and neoplastic transformation is
      made.

PMID- 8302723
TI  - Effects of octreotide on morphology of pituitary adenomas in acromegaly.
AB  - We studied the effects of the long-acting somatostatin analogue octreotide (SMS
      201-995, Sandoz, Basel, Switzerland) on the morphology of pituitary adenomas in
      acromegaly. Of the 29 adenomas examined by light microscopy, 16 had been treated
      pre-operatively with octreotide. The treated adenomas were compared with the
      untreated adenomas. 14 adenomas were also studied by electron microscopy. In 23
      cases we performed in-situ-hybridization for GH-mRNA. Under light microscopy, we
      found a decrease in amyloid deposits and a higher amount of cell necroses and
      fibroses after treatment, mainly in the tumors with shrinkage. Tumor shrinkage
      was diagnosed when the maximal diameter of the adenoma decreased for at least 1/3
      during octreotide treatment in NMR examination. Immunohistochemical examinations
      showed that treated adenomas, especially those with tumor shrinkage, possessed
      more GH immunoreactive cells, and after in-situ-hybridization we found a higher
      content of GH-mRNA. On the ultrastructural level, rough endoplasmic reticulum
      appeared to be increased in treated adenomas. The increase of GH-mRNA and of
      rough endoplasmic reticulum suggests the likelihood of an increased secretory
      activity due to a rebound effect after short-term pre-operative omission of
      octreotide. Other findings are discussed.

PMID- 8302725
TI  - Pulmonary embolism and heart disease. An autopsy study.
AB  - The frequency of pulmonary embolism in patients with myocardial infarction (MI)
      and chronic rheumatic heart disease (RHE) has been investigated in an autopsy
      series. The series comprised 21530 hospital autopsies from 1960 to 1984.
      Altogether 5351 patients with MI and 289 patients with RHE as underlying death
      cause were selected for this study. Patients with RHE or old myocardial
      infarction (OMI) had a significantly higher frequency of pulmonary embolism than
      patients with acute myocardial infarction (AMI) or acute and old myocardial
      infarction combined (AOMI). This was true irrespective of duration of stay in the
      hospital during last admission. The frequency of pulmonary embolism decreased in
      patients with OMI or RHE from 1960 to 1984 suggestive of better therapy of
      chronic heart failure. A similar trend was seen in patients with AMI during a
      period with consistent anticoagulation treatment.

PMID- 8302724
TI  - Localization by in situ hybridization of mRNAs encoding stromelysin 3 and tissue
      inhibitors of metallo-proteinases TIMP-1 and TIMP-2 in human head and neck
      carcinomas.
AB  - The presence and distribution of mRNAs encoding a matrix metalloproteinase (MMP)
      stromelysin 3 and two tissue inhibitors of MMP, TIMP1 and TIMP-2 have been
      studied by in situ hybridization of 18 human epidermoid head and neck carcinomas
      and four normal tissues. We found that in 16 tumors out of 18, stromelysin 3
      mRNAs were only expressed by fibroblasts which were in close contact to invasive
      cancer cells. Tumor cells and normal tissues were not labeled. TIMP-1 mRNAs were
      detected in well differentiated cancer cells and in endothelial cells in all the
      cancers. In 13 out of the 18 carcinomas, TIMP-2 mRNAs were localized in only a
      few stromal cells near well differentiated invasive cancer cells and in
      endothelial cells. The significant expression of TIMP-1 and TIMP-2 mRNAS may lead
      to less aggressive MMPs, especially in the case of stromelysin 3, in the invasive
      process of the stroma.

PMID- 8302726
TI  - In-situ carcinoma adjacent to recurrent nasopharyngeal carcinoma. Evidence of a
      new growth?
AB  - Eighty biopsies from 74 patients with recurrent nasopharyngeal carcinoma
      diagnosed in the years 1988 to 1990 inculsive were reviewed. The overlying
      epithelium was assessed for the presence of in-situ malignant change using a
      Gomori reticulin stain in addition to the routine haematoxylin and eosin stain.
      In-situ change was seen in the overlying epithelium or adjacent epithelium in 11
      of these biopsies from 10 patients (13.5%). These changes were extensive and
      where normal epithelium was seen there was an abrupt transition from the normal
      to abnormal epithelium. As patients treated for NPC sustain such a high risk of
      developing another new growth, close and careful follow up of these patients will
      allow a good opportunity for research into the carcinogenesis of this tumor.

PMID- 8302728
TI  - Granulocytic sarcoma of the larynx preceding chronic myeloid leukemia.
AB  - The authors report one case of granulocytic sarcoma infiltrating the larynx and
      cervical lymph nodes in a 50-year-old smoking patient. At the time of diagnosis
      there was no clinical and laboratory evidence of acute myeloid leukemia or
      chronic myeloproliferative disease. Four months after diagnosis, bone marrow
      morphology was consistent with chronic myeloid leukemia, accelerated phase.
      Cytogenetic abnormalities (Ph 1 chromosome, t(1; 12) (p36; p13), and trisomy of
      chromosome 20) were also found in hemopoetic cells. Granulocytic sarcoma
      preceding installation of chronic myeloid leukemia, as described here, seems to
      be a rare clinical event.

PMID- 8302727
TI  - CEA reactivity in amelanotic malignant melanoma of the anal canal.
AB  - Amelanotic malignant melanoma can present a diagnostic problem in histopathology,
      especially when it presents in an extracutaneous location. In such cases electron
      microscopy and/or immunohistochemistry are invaluable for diagnosis. A 63-year
      old women with rectal bleeding was found to have an amelanotic malignant melanoma
      of the anal canal, with compatible clinical and gross pathology and light and
      electron microscopic findings. Tumor cells showed positive staining with
      antibodies to vimentin, S 100 protein, and HMB-45 (melanoma-specific antibody),
      but also with polyclonal antibody to carcinoembryonic antigen (CEA). Tumor cells
      failed to stain with monoclonal antibody to CEA. The nature and significance of
      CEA reactivity in malignant melanoma are discussed.

PMID- 8302729
TI  - Lipid-rich adenoma of the thyroid.
AB  - A case of clear cell adenoma of the thyroid associated with an anaplastic spindle
      cell carcinoma is reported. Histochemical and ultrastructural examination showed
      abundant cytoplasmic lipid inclusions and frequent cytoplasmic vesicles, which
      both may have contributed to the clear cell change. The follicular cell origin
      was demonstrated by thyroglobulin positivity using immunohistochemistry. We
      believe that this adenomatous lesion shows close similarities with the lipid-rich
      cell adenoma first described by Schroder et al. in 1984.

PMID- 8302730
TI  - Immunohistochemical analysis of E-cadherin expression in human colorectal
      tumours.
AB  - The homotypic homophilic cell-cell adhesion molecule E-cadherin is crucial in the
      organization and maintenance of most epithelia. The expression of E-cadherin was
      studied immunohistochemically in various human colorectal tumours. Therefore we
      stained 1 tubular adenoma with low grade dysplasia, 18 adenocarcinomas with
      different histologic degrees of differentiation and invasion, and 1 metastasis
      using a modified peroxidase-anti-peroxidase technique. In the adenoma as well as
      in all well differentiated adenocarcinomas we found E-cadherin immunopositivity
      at the cell membrane of almost all cancer cells. The immunopositivity of E
      cadherin was clearly weaker and sometimes even absent in isolated neoplastic
      cells and glands of less differentiated adenocarcinomas. The moderately
      differentiated adenocarcinomas showed an intermediate staining pattern. These
      findings are in line with experimental evidence that downregulation of E-cadherin
      favours invasion, eventually leading to metastasis.

PMID- 8302731
TI  - Expression of cytochrome b558 on B cell- and CD 30 positive-lymphomas.
AB  - Expression of cytochrome b558, an essential constituent of the superoxide
      generating system in phagocytes, was demonstrated in B-lymphocytes. To determine
      its expression in malignant lymphoma (ML), 103 non-Hodgkin's MLs and 18 Hodgkin's
      (HD) MLs, together with non-tumorous lymphoid tissues were immunohistochemically
      analyzed, using two antibodies specific for the cytochrome. In non-tumorous
      tonsils and lymph nodes, B-lymphocytes, especially in the mantle zones, and
      histiocytes stained heavily, while T-lymphocytes failed to stain. Among the 55 B
      MLs, all follicular lymphomas (9/9) and 18/46 of the diffuse lymphomas were found
      to express cytochrome b558. Among 48 T-MLs, 46 were unstained by antibodies
      against the cytochrome. The two cytochrome b558-positive cases were CD 30
      positive anaplastic large cell lymphomas. Sixteen of 18 HD patients had CD 30
      positive Reed-Sternberg cells which also stained with antibody alpha LC (an
      anticytochrome b558 antibody). Thus, cytochrome b558, represents a new lymphocyte
      differentiation antigen.

PMID- 8302732
TI  - Detection of the lymphokine migration inhibitory factor in normal and disease
      affected lung by antibody and by its major binding protein, the interferon
      antagonist sarcolectin.
AB  - Human migration inhibitory factor (MIF) is suggested to play a notable role in
      regulation of macrophage functions in host defense. A major binding component for
      the lymphokine in human tissue is the interferon antagonist sarcolectin. This
      high-affinity interaction gives access to MIF by affinity chromatography on
      immobilized sarcolectin and may be of significance for in situ activity of MIF.
      Localization of MIF is one step towards answering this question. Labelled
      sarcolectin and MIF-specific antibodies can be employed to analyze the expression
      of the factor. Surgical specimens of 74 patients, who underwent lobe/lung
      resection or diagnostic biopsy, were fixed with buffered formalin and embedded in
      paraffin. The material consisted of 36 cases of morphologically normal lung
      parenchyma of patients, suffering from bronchial carcinoma, of 16 cases with
      sarcoidosis, of 15 cases with tuberculosis and of 7 cases with idiopathic
      interstitial pneumonitis. The two types of probe to visualize presence of MIF
      invariably showed the same level of reactivity, underscoring the potential
      physiological significance of sarcolectin-MIF interaction. In detail, all cases
      with pneumonitis, most tuberculosis-affected as well as normal cases and 44% of
      the cases with sarcoidosis were positive. All positive cases with sarcoidosis and
      some cases from the other groups revealed accessible binding sites for
      biotinylated MIF.

PMID- 8302733
TI  - Prognostic value of p53 protein expression in breast carcinomas.
AB  - A group of 196 ductal infiltrating carcinomas of the breast was examined
      immunohistochemically for p53. The purpose of this study was to show whether
      frozen and fixed tissues are equally adequate for detection of p53 and which
      antibodies should be used to have a prognostic value. Detection was superior on
      frozen to that on formalin-fixed tissues. It was not possible with any method to
      improve results on fixed tissues. Detection of p53 was different for each
      antibody: M 1801 detected 41 cases on frozen tissues, M-240 52 cases, M-421 28
      cases. Using all the antisera, and the rabbit antiserum CM1, it was possible to
      detect 71 cases (36%). The percentage was the same in infiltrating lobular
      carcinomas but higher (94%) in medullary carcinomas. p53 was associated with high
      grade and ER-tumours. In formalin-fixed tissues, p53 had no prognostic value. In
      frozen tissues p53 was not an independent factor of prognosis. However, it was
      important in sorting out cases with bad prognosis in the ER-carcinomas and in the
      carcinomas without metastases. The prognostic value was different for each
      monoclonal antiserum. Positivity with M421 associated with negativity for M240,
      and positivity only for M1801 sorted out cases with a poor prognosis (67% and 50%
      deaths at 5 years).

PMID- 8302734
TI  - The current management of vascular birthmarks.
AB  - Two vascular birthmarks are hemangiomas and vascular malformations. Hemangiomas
      grow by cellular proliferation. Their hallmark is rapid neonatal growth.
      Spontaneous regression begins when the infant is 6 to 10 months old, but it may
      continue until 8 to 10 years of age. Hemangiomas are infrequently life
      threatening. Pharmacologic treatment is indispensible; unsightly sequelae require
      surgical treatment. Vascular malformations consist of dysplastic vessels and are
      present on a lifelong basis. They are either slow-flow (capillary, venous,
      lymphatic) or fast-flow anomalies with arteriovenous shunting. Complex combined
      vascular malformations are observed as well. Ten years ago angiographic studies
      clearly demonstrated the differences among the various lesions. Today a
      noninvasive diagnostic approach is recommended, particularly in children.
      Ultrasonography, Doppler flow imaging, and magnetic resonance imaging are the
      most informative techniques, revealing the extent of tissue involvement and
      differentiating fast-flow from slow-flow anomalies. Risks and management differ
      depending on the type of vascular malformation.

PMID- 8302735
TI  - Severe skin erosions and scalp infections in AEC syndrome.
AB  - Hay-Wells syndrome is an autosomal dominant condition characterized by
      ankyloblepharon filiforme adnatum, ectodermal dysplasia, and cleft palate with or
      without associated cleft lip (AEC syndrome). Although several reported patients
      had eroded skin at birth and recurrent scalp infections, these are not generally
      regarded as major features of the disorder. In our experience, denuded skin at
      birth and chronic scalp erosions complicated by infection are common features of
      this syndrome. Aggressive wound care in conjunction with early administration of
      topical or systemic antibiotics is suggested.

PMID- 8302736
TI  - Congenital hemangioma of eccrine sweat glands.
AB  - We present six patients with congenital hemangioma of eccrine sweat glands. In
      every one the lesion was congenital, clinically angiomatous, painless, and
      nonsweating, with progressive involution over months. Histologically all
      specimens showed many dilated capillaries with prominent endothelial cells
      associated with the eccrine sweat gland coils.

PMID- 8302737
TI  - An X-linked reticulate pigmentary disorder with systemic manifestations: report
      of a second family.
AB  - Another family manifesting an X-linked, reticulate, pigmentary dermatosis,
      previously familial cutaneous amyloidosis, has been observed. The disorder is
      characterized in males in this family by onset in the first year of recurrent
      episodes of respiratory illness including pneumonia, a progressive reticulate
      pigmentation of the skin, hypohidrosis, and photophobia. The absence of amyloid
      deposits in the skin in both the mother and sons confirms that less emphasis
      should be given to the word "amyloidosis" in naming the disorder.

PMID- 8302738
TI  - Cutaneous amebiasis in children.
AB  - A 7-month-old girl developed cutaneous amebiasis of the perianal and genital
      areas in association with amebic dysentery. The diagnosis was based on the
      identification of Entamoeba histolytica by skin biopsy. She was treated with
      dehydroemetine and metronidazole with excellent results. This is only the eighth
      reported case of this disease in a child.

PMID- 8302740
TI  - Onychodystrophy in lichen striatus.
AB  - Lichen striatus is a common childhood eruption, but only rare reports link
      cutaneous manifestations and onychodystrophy. We report a case of lichen striatus
      and onychodystrophy in a 12-year-old girl, only the eighth such patient in the
      dermatologic literature. Nail changes may precede the rash of lichen striatus and
      should be considered in the differential diagnosis of isolated nail dystrophy in
      children.

PMID- 8302739
TI  - Dermatosis papulosa nigra in a young child.
AB  - Dermatosis papulosa nigra was diagnosed in a 3-year-old black boy. This
      follicular nevoid condition, which is common in adult blacks, is seldom diagnosed
      in prepubescent children. The diagnosis was confirmed by the biopsy specimen that
      showed features of epidermal acanthosis and papillomatosis, similar to seborrheic
      keratosis.

PMID- 8302741
TI  - Dyskeratosis congenita or chronic graft-versus-host disease? A diagnostic dilemma
      in a child eight years after bone marrow transplantation for aplastic anemia.
AB  - A 12-year-old boy had striking reticulate hyperpigmentation of the neck and upper
      chest, dystrophic nails, patchy alopecia, and a white streak on the buccal
      mucosa. He was diagnosed as having chronic graft-versus-host disease (GVHD) based
      on clinical findings, skin biopsy findings, and his history of a bone marrow
      transplantation for aplastic anemia eight years earlier. Dyskeratosis congenita
      (DC) was not a diagnostic consideration, although the clinical findings and
      history of aplastic anemia made it a compelling possibility. This case highlights
      the clinical similarities between DC and chronic GVHD and the difficulty in
      arriving at an unequivocal diagnosis.

PMID- 8302742
TI  - Streptococcal vulvovaginitis in girls.
AB  - Group A beta-hemolytic Streptococcus (GAHS) was isolated from 18% of swabs
      submitted to a district microbiology laboratory from girls with vulvovaginitis, a
      figure similar to that from a contemporary British study. This suggests that
      vulvovaginitis is more commonly associated with GAHS than reported previously.
      This could represent either an increase in frequency of the condition or better
      recognition of it.

PMID- 8302743
TI  - Diaper dermatitis due to Trichophyton verrucosum.

PMID- 8302745
TI  - Partial improvement of Olmsted syndrome with etretinate.
AB  - An 11-year-old Japanese boy with Olmsted syndrome was seen at our clinic. He had
      a sharply marginated, painful keratoderma with a red border on his palms and
      soles. Flexion contractures of the fingers were also observed. Hyperkeratotic
      plaques were present below the lower lip, on the elbows and knees, and in the
      sacral area. Localized alopecia, leukokeratosis on the tongue, shortness of
      stature, and laxity of the large joints corresponded to the clinical features of
      Olmsted syndrome. Treatment with etretinate was effective for the palms and
      fingers, but resulted in no improvement of the keratoderma of the soles. Because
      of periosteal thickening of the tibia, presumably caused by etretinate, therapy
      was terminated one year after it began.

PMID- 8302744
TI  - Topical lidocaine for anesthesia in patients undergoing pulsed dye laser
      treatment for vascular malformations.
AB  - Pulsed dye laser treatment of vascular malformations is moderately painful.
      Twenty-five percent lidocaine in 70% dimethyl sulfoxide-ethanol was used to
      achieve anesthesia in patients undergoing the procedure. Thirteen of 14 patients
      had some degree of anesthesia (average of 51%) ranging from 10% to 100%, with 8
      of them experiencing good results (> 50% anesthesia). Diminishment of pain was
      assessed by comparison of laser therapy on lidocaine-treated versus untreated
      sites within the vascular malformation using verbal and visual analog scales. In
      vitro permeation demonstrated good absorption of lidocaine, peaking at one hour.
      Permeation of lidocaine was significantly greater then that observed from acid
      mantle cream or EMLA. Topical lidocaine at 25% concentration in dimethyl
      sulfoxide 70% was well tolerated and had no side effects except transient mild
      erythema.

PMID- 8302747
TI  - What syndrome is this? Trichorhinophalangeal syndrome.

PMID- 8302746
TI  - Centrofacial milia-like eruption.

PMID- 8302748
TI  - Acute guttate psoriasis after streptococcal scarlet fever.

PMID- 8302750
TI  - Alopecia.

PMID- 8302749
TI  - Scrotal hair growth in infancy.

PMID- 8302751
TI  - Waardenburg syndrome associated with congenital melanocytic nevus.

PMID- 8302752
TI  - Trichonodosis.

PMID- 8302753
TI  - Bullous lichen planus.

PMID- 8302754
TI  - Transport of ionic species in skin: contribution of pores to the overall skin
      conductance.
AB  - Two methods are reported that allow visualization of high conductance paths in
      skin at current densities typically used during clinical iontophoretic drug
      delivery (10-200 microA/cm2). In the first method, the counter-directional
      iontophoretic transport of Fe(CN)6(4-) and Fe3+ across skin results in the
      precipitation of colloidal prussian blue, Fe4[Fe(CN)6]3, at sites of high
      iontophoretic flux. The appearance of localized deposits of Fe4[Fe(CN)6]3 is
      recorded by video microscopy and used to document the activation of low
      resistance paths. In the second method, the ionic flux of Fe(CN)6(4-) through
      pores is directly imaged by scanning electrochemical microscopy (SECM). Both
      methods demonstrate that the iontophoretic flux across skin is highly localized.
      Activation of low-resistance pores in hairless mouse skin is shown to occur
      during iontophoresis. The spatial density of current carrying pores increases
      from 0 to 100-600 pores/cm2 during the first 30-60 min of iontophoresis. At
      longer times, the active pore density approaches a quasi-steady-state value that
      is proportional to the applied current density. The total conductance of the skin
      is proportional to the number of pores, consistent with a model of conduction in
      skin that is comprised of low-resistivity pores in parallel with a high
      resistivity bulk phase. The contribution of pores to the total skin conductance
      during iontophoresis increases from an initial value of 0-5% to a quasi-steady
      state value of 50-95%.

PMID- 8302755
TI  - A correlation between the permeability characteristics of a series of peptides
      using an in vitro cell culture model (Caco-2) and those using an in situ perfused
      rat ileum model of the intestinal mucosa.
AB  - In an attempt to establish an in vitro/in situ correlation of intestinal
      permeability data, the permeability coefficients (Papp) for a series of model
      peptides, which were determined using an in situ perfused rat ileum model, were
      compared to the permeability coefficients (Pmono) determined using an in vitro
      cell culture model (Caco-2). The model peptides, which were all blocked on the N
      terminal (acetyl, Ac) and the C-terminal (amide, NH2) ends, consisted of D
      phenylalanine (F) residues (e.g., AcFNH2, AcFFNH2, AcFFFNH2). To alter the degree
      of hydrogen bonding potential, the nitrogens of the amide bonds were sequentially
      methylated [e.g., AcFF(Me)FNH2, AcF(Me)F(Me)FNH2, Ac(Me)F(Me)FNH2,
      Ac(Me)F(Me)F(Me)]. These peptides were shown not to be metabolized in the in situ
      perfused rat ileum system. The results of the transport experiments showed that
      there were poor correlations between the apparent permeability coefficients
      (Papp) determined in an in situ perfused rat ileum model and the octanol-water
      partition coefficients (r = 0.60) or the hydrogen bonding numbers (r = 0.63) of
      these peptides. However, good correlations were observed between the in situ Papp
      values for these peptides and their partition coefficients in heptane-ethylene
      glycol (r = 0.96) and the differences in their partition coefficients between
      octanol-water and isooctane-water (r = 0.86). These results suggest that
      lipophilicity may not be the major factor in determining the intestinal
      permeability of these peptides and that hydrogen bonding potential may be a major
      contributing factor. These results suggest that lipophilicity may not be the
      major factor in determining the intestinal permeability of these peptides and
      that hydrogen bonding potential may be a major contributing factor.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8302756
TI  - Interleukin-2-containing liposomes: interaction of interleukin-2 with liposomal
      bilayers and preliminary studies on application in cancer vaccines.
AB  - Interleukin-2 (IL-2) incorporation in liposomes was studied under different
      conditions. Information was obtained on the mechanism of interaction of
      glycosylated recombinant IL-2 with liposomal bilayers. This information was
      utilized to formulate liposomes with high levels of incorporated IL-2.
      Multilamellar vesicles were prepared by hydration of a lipid film with an IL-2
      solution. The incorporation efficiency, measured with a bioassay after forced
      release of IL-2 from the vesicles, was strongly dependent on the charge of the
      liposomes and the pH and ionic strength of the hydration medium. Negatively
      charged liposomes composed of phosphatidylcholine/phosphatidylglycerol (9:1) and
      prepared with IL-2 dissolved in 10 mM NaAc/270 mM glycerol, 0.1% BSA, pH 5,
      showed the highest incorporation efficiency (81%) among the investigated
      preparations. This type of liposome was selected for further study.
      Electrostatics play a crucial role in the process of IL-2 association with this
      type of liposome. Initial studies concerning induction of protective tumor
      immunity by immunization with reconstituted membranes with muramyl tripeptide
      phosphatidylethanolamine indicate that coinjection of IL-2-containing liposomes
      provided a significant enhancement of the immune response.

PMID- 8302758
TI  - Phonophoresis of methyl nicotinate: a preliminary study to elucidate the
      mechanism of action.
AB  - The skin penetration enhancement effect of ultrasound (phonophoresis) on methyl
      nicotinate was investigated in 10 healthy volunteers in a double-blind, placebo
      controlled, crossover clinical trial. Each treatment consisted of the application
      of ultrasound massage (3.0 MHz, 1.0 W/cm2 continuous output) or placebo massage
      (0 MHz) for 5 min to the forearms of the volunteers, followed by a standardized
      application of methyl nicotinate at intervals of 15 sec, 1 min, and 2 min post
      massage. Percutaneous absorption of methyl nicotinate was monitored using laser
      Doppler velocimetry. Ultrasound treatment applied prior to methyl nicotinate led
      to enhanced percutaneous absorption of the drug, for example, ultrasound
      treatment data versus control data at 2 min showed significant increases (P <
      0.05; analysis of variance) in the peak blood flow (125.8 +/- 12.0 vs 75.3 +/-
      10.4% flux) and in the area under the curve for blood flow (2630.3 +/- 387.5 vs
      1567.6 +/- 183.5% flux.min). The results of this study suggest that ultrasound
      affects the skin structure to provide skin penetration enhancement. This finding
      is consistent with the proposed hypothesis that phonophoresis acts by disordering
      the structured lipids in the stratum corneum.

PMID- 8302757
TI  - Mechanism of intestinal absorption of ranitidine and ondansetron: transport
      across Caco-2 cell monolayers.
AB  - We have investigated the transport of ranitidine and ondansetron across the Caco
      2 cell monolayers. The apparent permeability co-efficients (Papp) were unchanged
      throughout the concentration range studied, indicating a passive diffusion
      pathway across intestinal mucosa. No metabolism was observed for ranitidine and
      ondansetron during the incubation with Caco-2 cell monolayers. Papp values for
      ranitidine and ondansetron (bioavailability of 50 and approximately 100% in
      humans, respectively) were 1.03 +/- 0.17 x 10(-7) and 1.83 +/- 0.055 x 10(-5)
      cm/sec, respectively. The Papp value for ranitidine was increased by 15- to 20
      fold in a calcium-free medium or in the transport medium containing EDTA, whereas
      no significant change occurred with ondansetron, indicating that paracellular
      passive diffusion is not rate determining for ondansetron. Uptake of ondansetron
      by Caco-2 cell monolayers was 20- and 5-fold higher than that of ranitidine when
      the uptake study was carried out under sink conditions and at steady state. These
      results suggest that ranitidine and ondansetron are transported across Caco-2
      cell monolayers predominantly via paracellular and transcellular pathways,
      respectively.

PMID- 8302759
TI  - Site-specific drug delivery to pilosebaceous structures using polymeric
      microspheres.
AB  - In order to improve the therapeutic index of adapalene, a new drug under
      development for the treatment of acne, site-specific delivery to the hair
      follicles using 50:50 poly(DL-lactic-co-glycolic acid) microspheres as
      particulate carriers was investigated in vitro and in vivo. The percutaneous
      penetration pathway of the microspheres was shown to be dependent on their mean
      diameter. Thus, after topical application onto hairless rat or human skin,
      adapalene-loaded microspheres (5-microns diameter) were specifically targeted to
      the follicular ducts and did not penetrate via the stratum corneum. The in vitro
      release of adapalene from the microspheres into artificial sebum at 37 degrees C
      was controlled and faster than the in vivo sebum excretion in humans. Aiming to
      reduce either the applied dose of drug or the frequency of administration,
      different formulations of adapalene-loaded microspheres were evaluated in vivo in
      the rhino mouse model. A dose-related comedolytic activity of topical
      formulations of adapalene-loaded microspheres was observed in this model.
      Furthermore, by applying a site-specific drug delivery system (0.1% adapalene)
      every other day or by administering a 10-fold less concentrated targeted
      formulation (0.01%) every day, a pharmacological activity equivalent to a daily
      application of an aqueous gel containing drug crystals (0.1% adapalene) was
      observed. Since an aqueous gel containing 10% adapalene-loaded microspheres was
      not irritating in a rabbit skin irritancy test, this formulation was applied onto
      forearms of human volunteers. Site-specific drug delivery was further evidenced
      by follicular biopsy. Since an aqueous gel containing 10% adapalene-loaded
      microspheres was not irritating in a rabbit skin irritancy test, this formulation
      was applied onto forearms of human volunteers. Site-specific drug delivery was
      further evidenced by follicular biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302760
TI  - Disparity of in vitro and in vivo oleic acid-enhanced beta-estradiol percutaneous
      absorption across human skin.
AB  - The permeation enhancing property of 5% oleic acid in ethanol on beta-estradiol
      was investigated in vitro and in vivo using symmetrical and asymmetrical side-by
      side diffusion cells and the human skin sandwich flap, respectively. beta
      Estradiol permeability in vitro and in vivo was similar in 75% ethanol (ETOH).
      Oleic acid (5%) did not alter beta-estradiol permeability in vivo but increased
      permeability six-fold in vitro in symmetrical diffusion cells. beta-Estradiol
      permeability in oleic acid was not different from that in ETOH, however, using
      asymmetrical diffusion cells. Stratum corneum-to-vehicle partition coefficients
      of beta-estradiol in the vehicles were similar, yet fourfold more steroid was
      detected in skin biopsies from the in vitro symmetrical diffusion cells. Thus,
      oleic acid increased beta-estradiol permeability in vitro only when skin was
      equilibrated with fatty acid. Attention to in vitro diffusion cell design and its
      relevance in vivo is critical to defining the mechanisms of enhanced solute
      permeation.

PMID- 8302761
TI  - Reverse iontophoresis: development of a noninvasive approach for glucose
      monitoring.
AB  - Solvent flow generated during iontophoresis can be used to convect neutral
      molecules through the skin, thereby greatly enhancing their flux. This concept
      was exploited to realize noninvasive glucose measurement by its iontophoretic
      extraction from the subcutaneous tissue. The hypothesis was tested in vitro using
      hairless mouse skin. The dermal surface was bathed with a glucose solution;
      chambers on the epidermal surface housed the current delivery electrodes.
      Iontophoresis (at 0.36 mA/cm2) was performed for 2 hr, at the end of which the
      solutions in contact with the electrodes were analyzed. The amount extracted was
      proportional to the glucose solution concentration bathing the dermis. Higher
      radioactivity levels were found at the anode than at the cathode, possibly
      because of glucose metabolism during its outward transport across the skin.
      Glucose biotransformation results in negatively charged metabolites which migrate
      to the anode. Two sensitive glucose sensors were developed; one was selective for
      glucose, the other for glucose and related compounds. Both sensors indicated the
      presence of glucose at the cathode but an abnormally high value was also recorded
      at the anode. This signal, however, was not due to glucose but rather to
      electroactive ascorbate withdrawn from the skin. Finally, a system has been
      developed with which glucose can be extracted noninvasively from the subcutaneous
      tissue and unambiguously measured. Whether iontophoretic glucose sampling in vivo
      will be equally successful remains to be answered.

PMID- 8302762
TI  - Influence of skin irritants on percutaneous absorption.
AB  - The effects of the application of skin irritants on the in vitro percutaneous
      absorption of three model compounds of diverse physico-chemical properties,
      caffeine, indomethacin, and hydrocortisone, were investigated. Norephedrine and
      imipramine, basic drugs with a known skin irritation potential, were employed to
      damage the skin. Treatment with norephedrine increased the permeation of caffeine
      and hydrocortisone by two- to fourfold, while absorption of indomethacin declined
      an order of magnitude. A similar result was obtained for the effect of treatment
      with imipramine on transport of caffeine. Pretreatment with imipramine promoted
      hydrocortisone absorption 10-fold but, unlike norephedrine, did not alter
      indomethacin permeation. While both treatments in vivo caused an increase
      (norephedrine > imipramine) in the pH on the surface of skin and after tape
      stripping the skin, only norephedrine caused changes in transepidermal water loss
      in vivo in man. Since imipramine was the more severe irritant as judged by
      erythema, alterations by irritants of barrier function appeared rather complex.

PMID- 8302763
TI  - Dose proportionality and population characteristics of oral fadrozole
      hydrochloride, an aromatase inhibitor, in postmenopausal women.
AB  - The dose proportionality of the pharmacokinetics of fadrozole was investigated in
      18 healthy postmenopausal women. Fadrozole hydrochloride was administered as 0.3
      , 1.0-, and 2.0-mg oral doses continuously every 12 hr for 5 days each in a Latin
      square design. At steady state, the dose-normalized pharmacokinetic parameters
      AUC and Cmax were found to be independent of the dose. In addition, no
      statistically significant differences in tmax were detected. It was concluded
      that the pharmacokinetics of fadrozole were dose proportional in the projected
      therapeutic dose range. The relationship between oral clearance and the
      demographic factors, age, weight, and height, was assessed. Oral clearance was
      related to total body weight but not age or height. Prospective estimates of the
      population components of variance showed that intersubject variance accounted for
      91.7% of the total random variance. Weight variance accounted for 36.1% of the
      intersubject variance.

PMID- 8302764
TI  - Assessment of valproic acid serum-cerebrospinal fluid transport by microdialysis.
AB  - The systemic disposition and serum-cerebrospinal fluid (CSF) translocation of
      valproic acid (VPA) were examined in rats after administration of VPA as a bolus,
      as a continuous infusion, or with probenecid. VPA in CSF was monitored
      continuously by in vivo microdialysis. Both prolonged VPA infusion and probenecid
      pretreatment increased the Km for saturable VPA elimination and decreased
      intrinsic hepatic clearance, perhaps due to competition of probenecid or
      accumulated VPA metabolites for glucuronidation or depletion of hepatic UDP
      glucuronic acid. The CSF/serum VPA ratio increased rapidly initially, then
      decreased with time throughout the remainder of the experiment in all three
      groups. This time- and/or concentration-dependent behavior suggested that the
      rate of CSF penetration increased disproportionately with increasing serum VPA
      and could be described by a kinetic model incorporating a concentration-dependent
      first-order rate constant for VPA influx into CSF. Under all experimental
      conditions, the VPA efflux from CSF appeared to be saturable; an increase in the
      Michaelis constant for efflux was observed following probenecid pretreatment and
      during VPA infusion, suggesting competitive inhibition of transport by probenecid
      and derived metabolites of VPA, respectively. The mechanisms responsible for
      asymmetric VPA transport between serum and CSF, in particular the apparent
      concentration-dependent change in the rate constant governing CSF penetration,
      remain to be elucidated.

PMID- 8302766
TI  - Identification and isolation of chlorhexidine digluconate impurities.
AB  - We report the identification of 11 impurities in variously stressed chlorhexidine
      digluconate (CHG) solutions. The structural assignment of each CHG impurity
      involved tentative identification from HPLC-MS data followed by synthesis of the
      appropriate standard, isolation of the impurity from the CHG solution by flash
      chromatography, and comparison of HPLC-MS, HPLC-UV, and NMR data of the impurity
      with the standard. Six of the synthetic impurity standards represent new
      compounds. Degradation studies of CHG solutions systematically stressed by heat,
      light, and low pH are reported with identification and approximate quantification
      of resulting impurities. Degradation mechanisms were proposed for each set of
      stress conditions applied to CHG solutions. Parallels were noted between the way
      CHG degrades in the thermospray interface of the HPLC-MS and the way CHG degrades
      with shelf time. Similarities were noted in the synthetic starting materials of
      CHG and the final degradation products.

PMID- 8302765
TI  - The qualitative and quantitative analysis of chlorpropamide polymorphic mixtures
      by near-infrared Fourier transform Raman spectroscopy.
AB  - We analyzed binary mixtures of polymorphs A and B of chlorpropamide ((1-[4
      chlorobenzenesulphonyl]-3-propyl urea)) by near-infrared Fourier transform Raman
      spectroscopy (FTRS). The individual polymorphs were prepared and characterized by
      differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR)
      microscopy, and physical appearance. The FTR spectra of the two polymorphs showed
      distinct differences which result from "crystal splitting" effects. A series of
      13 different mixtures of polymorph A and B was prepared by geometric mixing and
      their FTR spectra statistically analysed by factor analysis programming.
      Predictions of the A/B polymorphic composition of mixtures were made and compared
      with the theoretical values. The results demonstrate that FTRS combined with
      factor analysis programming may be successfully applied to the in situ monitoring
      of the A/B polymorphic nature of a chlorpropamide sample.

PMID- 8302767
TI  - In vitro/in vivo models for peptide oral absorption: comparison of Caco-2 cell
      permeability with rat intestinal absorption of renin inhibitory peptides.

PMID- 8302768
TI  - Thermal analysis and solution calorimetry studies on losartan polymorphs.

PMID- 8302769
TI  - Binding and transport of some bioadhesive plant lectins across Caco-2 cell
      monolayers.

PMID- 8302770
TI  - Scaleup of oral extended-release dosage forms.

PMID- 8302771
TI  - Neuromelanin: a key to Parkinson's disease.

PMID- 8302772
TI  - From the crest to the periphery: control of pigment cell migration and lineage
      segregation.
AB  - Pigment cells are one of many cell types derived from the neural crest. This
      review focuses on the mechanisms that control the timing and pathways of
      migration of pigment cells into the epidermis and determinants that control the
      differentiation of pigment cells. Several factors may control the timing and
      pattern of pigment cell migration in the dorsolateral space including the loss of
      inhibitory molecules in the pathway, the appearance of chemotactic molecules
      emanating from the dispersing dermatome, and the differentiation of pigment
      cells, which may be the only neural crest derivative capable of utilizing the
      substratum found in the dorsolateral path. Control of pigment cell
      differentiation remains controversial. A working model presented in this review
      suggests that multipotent neural crest cells that disperse ventrally upon
      separation from the neural tube preserve neurogenic ability and lose melanogenic
      ability, whereas those cells that are arrested at the entrance to the
      dorsolateral path lose neurogenic ability so that the population becomes
      primarily melanogenic. During the time that the latter population is arrested in
      migration it is speculated that the neural crest cells are exposed to an
      environment comprised of specific extracellular matrix molecules and/or growth
      factors that enhance pigment cell differentiation.

PMID- 8302773
TI  - Role of melanin as a scavenger of active oxygen species.
AB  - The protective role of melanin, either synthetic or derived from a metastatic
      lung melanoma nodule, was studied in terms of its ability to interact with active
      oxygen species (O2., H2O2, RO., ROO., etc.). Both melanins showed the ability to
      react with O2.. The superoxide dismutase-like activity corresponds to 21 and 10
      U/mg for synthetic and tumor melanin, respectively. The latter value accounts for
      about 8% of the superoxide dismutase activity of cultured melanoma cells. Neither
      type of melanin showed catalase-like or glutathione peroxidase-like activity.
      Both types of melanin reacted with RO. and ROO. radicals as determined by
      inhibition of the lipid peroxidation reaction of rat liver homogenates. The
      spontaneous lipid peroxidation of rat liver homogenate was inhibited up to 90%
      and 80% by synthetic and tumor melanin with half-maximal effects at 2.5 and 5.5
      micrograms melanin/ml, respectively. The 2,2-azo-bis-(2 amidino propane) (AAPH)
      initiated lipid peroxidation of rat liver homogenate was inhibited up to 30% and
      20% by synthetic and tumor melanin, with half maximal effect at 120 and 500
      micrograms melanin/ml, respectively. Both types of melanin were able to protect
      the in vitro inactivation of glucose oxidase, which occurs in the presence of
      AAPH-generated radicals.

PMID- 8302774
TI  - Antimelanoma activity of chloroquine, an antimalarial agent with high affinity
      for melanin.
AB  - The antimalarial agent chloroquine is known for high affinity for melanin. This 4
      aminoquinoline derivative was examined for anti-melanoma activity and uptake into
      melanoma cells. Chloroquine inhibited growth of cultured melanoma cells; the
      effect was much greater to a moderately pigmented cell line HMV-II than to a
      nonpigmented HMV-I. Treatment with chloroquine at a dose of 62 mg/kg i.p. for 12
      days prolonged by 71% the life span of mice bearing B16 melanoma, while 24-day
      treatment at 31 mg/kg resulted in a 81% increase in life span. HMV-II cells
      showed a two-fold increase in uptake of chloroquine as compared with HMV-I cells.
      Chloroquine, 24 hr after administration to mice implanted s.c. with B16 melanoma,
      was selectively accumulated in the pigmented tissues, melanoma and eyes. Other
      nonpigmented tissues such as the liver, lung, and kidney showed rapid uptake
      (within 1 hr) and release. These results suggest that chloroquine is toxic to
      pigmented melanoma cells, the process being partly mediated by binding to
      melanin.

PMID- 8302775
TI  - Actin and tubulin arrays in cultured Xenopus melanophores responding to
      melatonin.
AB  - Melatonin induces pigment granule aggregation in amphibian melanophores. In the
      studies reported here, we have used fluorescence microscopic techniques to test
      the hypothesis that such melatonin-induced pigment movement is correlated with
      alterations in either the actin or tubulin cytoskeletal patterns of cultured
      Xenopus melanophores. In general, the cytoplasmic domains of the cultured
      melanophores were flat and thin except in the perinuclear region (especially when
      the pigment was aggregated). The microtubules and microfilaments were usually
      found in the same focal plane; however, on occasion, microfilaments were closer
      to the substratum. Microtubules were arranged in arrays radiating from what are
      presumed to be cytocenters. A small percentage of the melanophores were very
      large, had actin-rich circular perimeters and did not respond as rapidly to
      melatonin treatment as did the other melanophores. Melanophores with either
      aggregated or dispersed melanosomes had low intensity rhodamine-phalloidin
      staining of actin filaments compared to nonpigmented cells, whereas the FITC anti
      tubulin intensities were comparable in magnitude to that seen in nonpigmented
      cells. When cells were fixed prior to complete melatonin-induced pigment granule
      aggregation there was no abrupt diminution in either the tubulin or actin
      staining at the boundary between pigment granule-rich and pigment granule-poor
      cytoplasmic domains. Nor could the actin and tubulin patterns in cells with
      partially aggregated melanosomes be reliably distinguished from those in
      melanophores in which the melanosomes were either completely dispersed or
      completely aggregated. These data argue against the hypothesis that melatonin
      causes consistent large-scale rearrangements of tubulin and actin polymers as it
      induces pigment aggregation in Xenopus melanophores.

PMID- 8302776
TI  - [The child and tuberculosis].

PMID- 8302778
TI  - [Gastroesophageal reflux after percutaneous endoscopic gastrostomy. Scintigraphic
      study in 51 patients].
AB  - Gastro-oesophageal reflux and pneumonia are complications of enteral feeding. We
      report our experience of a scintigraphic technique in 51 patients fed by
      percutaneous endoscopic gastrostomy. The technique was very well tolerated; only
      one patient (2 percent) had vagal discomfort. A quantitative isotopic study using
      Tc 99 m labelled enteral infusion demonstrated episodes of reflux in 26 patients
      (51 percent). The reflux was greater than 6 percent of recording time in 15
      patients. All patients with pneumonia had positive scintigraphy. Our study
      suggests that reflux is frequent after percutaneous endoscopic gastrostomy and
      constant in patients with pneumonia.

PMID- 8302777
TI  - [Acute pyelonephritis in women. Short-term hospitalization].
AB  - One-hundred women suffering from acute pyelonephritis were hospitalized for less
      than 4 days on average, in order to make a diagnosis based on bacteriology and
      computerized tomography (CT) and to bring fever down with a 21-day antibiotic
      therapy. In cases of acute pyelonephritis due to a urinary tract obstacle,
      endoscopic uereteral drainage was added to the antibiotic treatment. In the
      absence of obstacle, medical treatment was sufficient to obtain apyrexia.
      Fluoroquinolone therapy made it possible to reduce the hospital stay to 2 or 3
      days, depending on whether the lesions observed at CT were triangular or round.

PMID- 8302779
TI  - [Risk of systematic celioscopic treatment of ovarian diseases. 2 cases].
AB  - We report 2 cases of malignant ovarian tumours. These tumours had been missed at
      a first laparoscopic examination, and a second examination detected the presence
      of cancer cells disseminated in the peritoneum and the abdominal wall. The risk
      of propagation of an overlooked cancer makes it necessary to carry out a
      preoperative thorough evaluation based on clinical and ultrasonographic data
      before any attempt at laparoscopic surgery. If a laparoscopic treatment is
      decided, it must be performed under strict conditions and include meticulous
      exploration of the abdominal cavity, systematic peritoneal cytology, needle
      cytology of the cyst, emptying of the cyst in a water-tight manner,
      extemporaneous biopsy in case of doubt, peritoneal cleansing, and extraction of
      the cyst or the ovary in a bag. If malignancy is suspected, laparotomy must be
      performed immediately.

PMID- 8302780
TI  - [Female pseudohermaphroditism].
AB  - Contrary to what is observed in true hermaphroditism and in male pseudo
      hermaphroditism, there is no erroneous transmission of the genetic gonadal
      differentiation programme in female pseudohermaphroditism. All that has happened
      is virilization of the urogenital sinus and external genitalia in a foetus
      exposed to exo- or endogenous androgens. In the absence of testis there is no
      production of anti-mullerian hormone, and for these reasons the uterus, the
      fallopian tubes and the vagina develop normally, whilst the wollfian ducts are
      regressed and there is no trace of male deep spermatic pathway. On the basis of
      recent acquisitions in biochemistry, endocrinology and embryogenesis, the authors
      compare the various degrees of virilization with the biochemical abnormalities.

PMID- 8302781
TI  - [Intravenous immunoglobulins in neurology].
AB  - Immunoglobulins, used at first empirically in the treatment of thrombocytopenic
      purpura, occupy a prominent place not only in the treatment of antibody
      deficiencies, but also in that of antoimmune diseases. Their indications in
      neurology are ever extending; they include myasthenia, chronic inflammatory
      polyneuropathies with or without monoclonal gammopathy, polymyositis,
      dermatomyositis and, more recently, disseminated sclerosis and Guillain-Barre
      syndrome. Even the therapeutic priority of plasmapheresis in this syndrome is
      disputed by some authors. Immunoglobulins are costly, but they are well tolerated
      and easy to use. Their effectiveness must be confirmed by controlled, double
      blind trials. In neurology such trials are still rare, but those recently
      published are devoid of methodological errors. Once the effectiveness of
      immunoglobulins is confirmed, their dosage must be established, and attempts
      should be made at a better understanding of their mechanisms of action.

PMID- 8302782
TI  - [Functional accessory adrenal gland in the course of Cushing's disease].

PMID- 8302783
TI  - [Fulminant cardiac and neurological complications in hypereosinophilic syndrome].

PMID- 8302784
TI  - ["Gloves and socks" papular purpura associated with antiphospholipid antibodies].

PMID- 8302785
TI  - [Hematomyelia under the effect of anticoagulants].

PMID- 8302786
TI  - [Congenital asplenia, a differential diagnosis of essential thrombocythemia].

PMID- 8302787
TI  - [Orthostatic hypotension revealing HIV infection].

PMID- 8302788
TI  - Lymph node involvement and pancreatic resection: correlation with prognosis and
      local disease control in a clinical trial.
AB  - In a prospectively randomized trial evaluating pancreatic resection with adjuvant
      radiotherapy (intraoperative radiotherapy [IORT] vs. external beam radiotherapy
      [EBRT]), lymph nodal involvement was examined and correlated with outcome. Twenty
      six patients underwent pancreatic resection and received either IORT or EBRT
      (Stages II-IV). Patients who were stage I received surgery alone. Regional nodal
      metastases were present in 15 of 26 (57%) patients. Seven patients suffered
      treatment-related mortality. Survival, mortality, and morbidity were unaffected
      by the type of radiotherapy. The survival of patients with negative nodes (median
      survival 24 months, range 10 to > 109) appeared superior to the survival of
      patients with nodal involvement (median survival 11.5 months; range 4-39). Even
      in patients with locally advanced disease extending into extrapancreatic tissues,
      two node-negative patients appeared to survive longer (12 and 53 months) than 10
      node-positive patients with similarly extensive local disease (median survival
      11.5 months; range 4-39). Local disease control, however, appeared to be
      independent of nodal involvement, with eventual local recurrences in 6 of 8 node
      negative patients and in 4 of 7 node-positive patients who were evaluable for
      local disease control by autopsy or by antemortem laparotomy.

PMID- 8302789
TI  - Low-dose octreotide treatment is not effective in patients with advanced
      pancreatic cancer.
AB  - Octreotide (SMS 201-995), a long-acting somatostatin analogue, has been shown to
      decelerate growth of human pancreatic cancer in vitro and in vivo. We analyzed
      the efficacy of octreotide treatment in 22 patients (14 men, 8 women) with
      histologically verified ductal pancreatic cancer. All patients had advanced tumor
      stages (stage III: 13 patients; stage IV: 9 patients). Octreotide was given by
      self-administered subcutaneous injection (3 x 100 micrograms/day). When there was
      evidence of tumor progression, the dose of octreotide was increased to 3 x 200
      micrograms/day. A monthly follow-up, including clinical status, CT scan or
      ultrasonography, and tumor marker carcinoembryonic antigen (CEA) and carbohydrate
      antigen (CA) 19-9 determination was carried out. There were no severe side
      effects apart from slight burning sensation at the injection site. No partial or
      complete remission was seen. Eighteen patients showed tumor progression with a
      median survival time of 17 weeks (range 3-42 weeks). In three patients a "no
      change" evaluation with a median survival time of 46 weeks (range 40-68 weeks)
      was registered. In these three patients the serum tumor markers CA 19-9 and CEA
      did not show an increase to more than twice the baseline value during this time.
      One patient discontinued the octreotide treatment because of tumor progression.
      The results of the analysis indicate that low-dose octreotide treatment is not
      effective in patient suffering from advanced tumor stages of pancreatic cancer.

PMID- 8302790
TI  - Comparative study of antibacterial activity of pancreatic juice in six mammalian
      species.
AB  - A comparative study of antibacterial activity of pancreatic juice was conducted
      on six mammalian species. Pancreatic juice collections were conducted as acute
      (rabbit, guinea pig, rat) and chronic (pig, sheep, cattle) experiments, in the
      former before and after stimulation [cholecystokinin (CCK) and secretin] and in
      the latter under basal conditions alone. Antibacterial activity was tested on
      Micrococcus pyogenes and compared with that of neomycin. The samples were tested
      under normal conditions and after heating and dilution. The pancreatic juice of
      rat showed no activity against Micrococcus pyogenes. The antibacterial activity
      of rabbit and guinea pig pancreatic juice under basal conditions was similar
      within the group but significantly higher than that of pig, sheep and cattle
      which also did not differ significantly within the group. On stimulation with CCK
      and secretin, no significant change could be observed in the potency of
      antimicrobial activity of pancreatic juice in the rabbit and guinea pig. The
      antibacterial activity remained unchanged after heating to 65 degrees C and upon
      dilution to 1:10.

PMID- 8302791
TI  - Bacterial translocation: a potential source for infection in acute pancreatitis.
AB  - Infections from enteric bacteria are a major cause of morbidity and mortality
      during acute pancreatitis (AP), but the pathways by which these organisms reach
      distant organs remains speculative. Experiments were conducted to determine if
      bacterial translocation could be a mechanism for infection during this disease.
      AP was induced in Lewis rats by i.v. infusion of caerulein (experiment I) or
      ligation of the head of the pancreas (experiment II). In a third experiment, rats
      were gavaged with 1 x 10(8) 14C-radiolabeled Escherichia coli and pancreatitis
      was induced with caerulein. Results in all three experiments showed that AP
      increased the number of viable bacteria recovered in peritoneal fluid, mesenteric
      lymph nodes (MLN), liver, lungs, and pancreas. Radionuclide counting indicated
      that AP enhanced the gut permeability to 14C E. coli. To estimate the impact of
      AP on the magnitude of translocation and on the ability of the host to clear
      bacteria, the nuclide and colony-forming units (CFU) ratios were calculated
      between animals with and without AP. Blood, peritoneal fluid, and MLN had the
      highest nuclide ratio. During AP, these tissues may be the principal routes for
      bacterial spreading from the gut lumen. Peritoneal fluid, pancreas, and lung were
      the tissues with the highest CFU ratio. Bacterial killing ability of these
      tissues is likely impaired during AP.

PMID- 8302792
TI  - Effect of treatment on the jejunal and colonic bacterial flora of dogs with
      exocrine pancreatic insufficiency.
AB  - The bacterial flora from the jejunum and colon of 19 dogs with naturally
      occurring exocrine pancreatic insufficiency (EPI) was examined. In six dogs with
      EPI that did not receive any treatment the bacterial count in the small intestine
      was > 10(6) colony-forming units (CFU)/g. This was consistent with bacterial
      overgrowth (BOG) (control dogs: < 10(5) CFU/g). Six dogs with EPI that received
      pancreatic enzyme supplementation and were in good condition had bacterial counts
      (> 10(6) CFU/g) that were nonsignificantly different from the untreated group.
      The remaining seven dogs with EPI that received both pancreatic enzyme
      supplementation and oral antibiotic therapy (tylosin), had bacterial flora counts
      that were significantly lower than the values in the other two groups of EPI
      dogs, and did not differ significantly from those of the control group. There
      were no statistical differences between the number of bacteria in the colon among
      the different groups of dogs with EPI and the control dogs. We conclude that the
      prevalence of BOG in dogs with EPI is high. Pancreatic enzyme supplementation did
      not affect the microflora of dogs with naturally occurring EPI. Oral antibiotic
      therapy with tylosin, however, effectively decreased BOG in these dogs.

PMID- 8302793
TI  - Symptomatic duodenal stenosis in chronic pancreatitis: a study of 17 cases in a
      medical-surgical series of 306 patients.
AB  - The aim of this study was to assess the prevalence, presentation, cause, and
      location of symptomatic duodenal stenosis, and its relation to the natural course
      of chronic pancreatitis in a medical-surgical series of 306 patients (86%
      alcoholics). Mean follow-up of the series was 7.9 years. Symptomatic duodenal
      stenosis occurred in 17 patients (5.6%). Diagnosis was confirmed by a barium
      series. The cause of stenosis was compression by the pancreatic head in all
      patients, associated with a pancreatic abscess in two. No pseudocysts were found
      at the time of diagnosis. The location was the 1st and 2nd part of the duodenum
      or the entire duodenal loop in 4, 6, and 7 patients, respectively. Cholestasis
      due to common bile duct stenosis occurred in association with duodenal stenosis
      in 9 patients. Fifteen patients were treated surgically; 11 for
      gastroenterostomy, and 4 for duodenopancreatectomy. Two patients were not treated
      surgically. We conclude that during the course of chronic pancreatitis,
      symptomatic duodenal stenosis occurred in 5.6% of patients, mainly during the
      first years of the clinical course of chronic pancreatitis, was due to pancreatic
      head compression and not pseudocysts, usually involved the 2nd part of the
      duodenum and, was associated with biliary stenosis in half of the cases. Since
      these two complications require surgery, common bile duct stenosis should be
      investigated when symptomatic duodenal stenosis is diagnosed.

PMID- 8302794
TI  - Smoking and alcoholic pancreatitis.
AB  - Only a small minority of alcoholics develop clinical evidence of pancreatitis.
      The reasons for this variation in individual susceptibility have not yet been
      defined. Recent studies have suggested that smoking may be a risk factor for the
      development of pancreatitis. However, there have been methodological problems
      with these studies regarding choice of controls and assessment of tobacco
      consumption. The present study was designed to determine whether smoking is a
      risk factor for pancreatitis in alcoholics. Tobacco consumption in alcoholics
      with pancreatitis was compared to that of alcoholics without pancreatitis
      (controls). Of 52 subjects with alcoholic pancreatitis, 86.5% were smokers
      compared with 87.2% of 47 alcoholic controls. Both daily and lifetime tobacco
      consumption in subjects with pancreatitis were less than those of alcoholic
      controls. Thus, there was no association between smoking and pancreatitis in this
      study. The previously described association between smoking and pancreatitis may
      be related to the high prevalence of smoking among alcoholics.

PMID- 8302795
TI  - Effect of sodium butyrate on glucose transport and glucose-phosphorylating
      enzymes in RIN-m5F cells.
AB  - Sodium butyrate is widely used to differentiate insulinoma cell lines. However,
      sodium has been shown to decrease glucose phosphorylation in the liver and heart
      and decrease the expression of glucose transporter. Since these mechanisms are
      essential for glucose-induced insulin secretion, the ultimate function of the
      pancreatic beta-cell, we investigated the effect of sodium butyrate on both
      glucose-phosphorylating enzymes as well as glucose transport in the pancreatic
      cell line RIN-m5F. Treatment of RIN-m5F cells with 2.5 mM sodium butyrate for 72
      h increased by twofold both hexokinase and glucokinase (GK) activities, as well
      as the gene expression of GK. Sodium butyrate treatment had no effect on GLUT-1
      mRNA levels but increased the GLUT-2 mRNA 3.7-fold. Kinetic analysis of 2
      deoxyglucose transport displayed a single curve with Km = 1.2 mM and Vmax = 10.9
      pmol/micrograms protein/min in the untreated cells, values similar to the low Km
      glucose transport reported in the pancreatic beta-cells. This low Km transport
      component markedly decreased with sodium butyrate treatment, and interestingly a
      second component with a higher Km appeared, consistent with the increase in GLUT
      2 mRNA. We conclude that the differentiating action of sodium butyrate involves
      increases in GK and GLUT-2 gene expression, which characterizes the
      differentiated state of the pancreatic beta-cell. However, the inhibitory effect
      of sodium butyrate on low Km glucose transport needs to be considered in the use
      of this compound to promote differentiation.

PMID- 8302797
TI  - Distribution of pancreatic macrophages preceding and during early insulitis in
      young NOD mice.
AB  - Indirect evidence suggests there may be early influx of beta-cell-directed
      macrophages into the islets of NOD mice, and before the onset of T-cell
      insulitis. We have therefore examined immunohistochemically the pancreas of young
      female NOD mice with monoclonal antibody F4/80 for the presence of macrophages in
      intraislet, peri-islet, exocrine, and perivascular regions preceding insulitis
      (days 18 and 22) and during early insulitis (days 30 and 40) and compared their
      distribution in age-matched normal Swiss mouse pancreas. In the absence of
      insulitis (day 18 and day 22) and during very early insulitis (day 30) macrophage
      positive cells had a predominantly exocrine and perivascular distribution with
      reduced numbers in the peri-islet area. Intraislet macrophages usually occurred
      singly and were sparse. At day 40, an enhanced influx of the immune cells was
      observed in intra- and peri-islet locations and in parallel with increased
      numbers in the exocrine areas. At this age, higher numbers of macrophages were
      observed within the islet, distributed among the T-cell infiltrate and also
      scattered among the endocrine cells. During the study period, the number of
      macrophages in the peri-, intraislet, and exocrine regions was significantly
      higher among NOD mice than in the Swiss mouse group (p = 0.003, p = 0.005, and p
      = 0.0009, respectively). In the absence of insulitis (days 18 and 22), although
      the number of positive cells tended to be higher in NOD mice, this difference
      reached statistical significance in the peri-islet area (p = 0.004).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8302796
TI  - Lithostathine, an inhibitor of CaCO3 crystal growth in pancreatic juice, induces
      bacterial aggregation.
AB  - Lithostathine is a pancreatic secretory protein which controls CaCO3 crystal
      growth in pancreatic juice. Trypsin hydrolysis of the molecule generates two
      fragments of 11 and 133 amino acids. The N-terminal undecapeptide bears the
      inhibitory activity for crystal growth. We demonstrate that the C-terminal part
      of the molecule, which is structurally related to Ca(2+)-dependent lectins, can
      induce bacterial aggregation. Ca(2+)- and pH-dependent aggregation was obtained
      for Escherichia coli strain KH 802 and 9 of 19 strains isolated from the
      predominant flora of human feces. Aggregation of E. coli could be reversed by
      dilution and bacteria could resume normal growth. Lithostathine is apparently the
      only component of normal pancreatic juice displaying such activity. Lithostathine
      is therefore a bifunctional protein which might be involved in the control of the
      bacterial ecosystem in the intestine.

PMID- 8302798
TI  - Effect of pancreatic denervation and atropine on the pancreatic response to
      secretin.
AB  - To study the influence of extrapancreatic nerves and intrapancreatic cholinergic
      activity on the pancreatic response to secretin, six dogs underwent
      extrapancreatic denervation and creation of pancreatic fistulae. A second group
      of six dogs had pancreatic fistulae created without pancreatic denervation. The
      pancreatic exocrine response to graded doses of secretin (16-500 ng/kg/h) was
      determined, both alone and during a background infusion of cholecystokinin
      octapeptide (CCK8, 50 ng/kg/h). All studies were replicated during administration
      of atropine (10 micrograms/kg/h). Secretin-induced bicarbonate output was
      significantly inhibited by atropine in both the innervated and denervated groups.
      Combined secretin and CCK8 elicited a dose-dependent increase in bicarbonate
      output and a sustained increase in protein output in both groups, regardless of
      atropine. In addition, potentiation of secretin-induced bicarbonate output by
      CCK8 was observed despite both extrinsic pancreatic denervation and
      administration of atropine. We conclude that endogenous intrapancreatic
      cholinergic activity influences the pancreatic response to secretin. Potentiation
      of secretin-induced bicarbonate output by CCK, however, is not dependent on
      neural mediation.

PMID- 8302799
TI  - Temporal expression of the gastrin (CCK-B) receptor during azaserine-induced
      pancreatic carcinogenesis.
AB  - Cholecystokinin (CCK-A) and gastrin (CCK-B) receptors have been demonstrated in
      the azaserine-induced rat pancreatic carcinoma DSL-6. In order to determine at
      what stage in azaserine-induced pancreatic carcinogenesis gastrin (CCK-B)
      receptors are first expressed, we examined the binding of [125I]gastrin-I to
      normal rat pancreas, azaserine-induced premalignant pancreatic nodules, grossly
      normal internodular pancreas, and DSL-6 carcinoma. We observed that specific
      gastrin binding was absent in normal pancreas, premalignant nodules, and
      internodular pancreas, and also reconfirmed our previous report of marked
      overexpression of gastrin (CCK-B) receptors in the DSL-6 carcinoma. Specific
      cholecystokinin (CCK) binding was present in all pancreatic tissue types tested.
      Therefore, we conclude that the presence of gastrin (CCK-B) receptors in the
      azaserine-induced pancreatic carcinoma DSL-6, in contrast to their absence in
      premalignant nodules, suggests that the expression of the gastrin (CCK-B)
      receptor may be important in the transformation from premalignant nodules to
      pancreatic cancer.

PMID- 8302800
TI  - Pancreatic function tests in the rat model of chronic pancreatic insufficiency.
AB  - It has recently been shown that the infusion of oleic acid into the rat
      pancreaticobiliary duct causes a reproducible and long-lasting atrophy of the
      exocrine pancreas. The effects of this pancreatic atrophy on non-invasive
      pancreatic function tests have not been fully characterized. This study was
      undertaken to determine which pancreatic function test was most useful in
      determining pancreatic insufficiency in this model. Pancreatic insufficiency (PI)
      was induced in male Wistar rats by oleic acid infusion and three pancreatic
      function tests were compared in these animals and saline controls. The
      coefficient of fat absorption on a 5 or 45% fat diet and bentiromide testing
      could not differentiate animals with or without PI, but fecal chymotrypsin levels
      were excellent discriminators. All animals with PI had fecal chymotrypsin levels
      below 67 U/g feces whereas all saline controls were above this level. We conclude
      that, in this model of PI, the fecal chymotrypsin concentration is the best non
      invasive test to determine pancreatic insufficiency.

PMID- 8302801
TI  - Feedback regulation of exocrine pancreatic secretion in dogs.
AB  - Important basic physiological mechanisms of exocrine pancreas secretion were
      delineated in a canine model. However, dogs have been considered unsuitable for
      the study of the controversial feedback regulation of exocrine pancreas
      secretion. The present study reveals a marked modification of pancreas secretion
      following the intraduodenal instillation of lipase: The postprandial lipase
      secretion decreases from 2,421 U x 180 min-1 to 1,490 U x 180 min-1, but
      simultaneously determined cholecystokinin (CCK) concentrations in plasma do not
      increase under these circumstances. The intraduodenal application of a protease
      inhibitor (800 mg camostate) significantly stimulates the secretion of the
      exocrine pancreas in the fasting dog: After 15 min the protein release increased
      to 133 +/- 30 mg. Intravenous atropine blocks this increase. The plasma
      concentrations of CCK are not significantly influenced. These results in our
      canine model show that the secretory activity of the exocrine pancreas depends on
      the intraduodenal enzyme content. CCK is irrelevant in this context.

PMID- 8302802
TI  - Primary mesenteric leiomyosarcoma masquerading as a pancreatic pseudocyst.

PMID- 8302803
TI  - Xanthogranulomatous change appearing in the pancreas cyst wall.

PMID- 8302804
TI  - Fibrous thickening of the main pancreatic duct wall showing localized stenosis on
      endoscopic retrograde cholangiopancreatography.

PMID- 8302805
TI  - Anti-cardiolipin antibody associated with acute hemorrhagic pancreatitis.

PMID- 8302806
TI  - Thrombotic cerebral arteriopathy in patients with the antiphospholipid syndrome.
AB  - OBJECTIVE: A distinctive type of chronic cerebral vasculopathy was identified in
      the small leptomeningeal arteries of patients with high levels of serum
      antiphospholipid antibodies. This study characterizes the vascular lesions and
      investigates their pathogenesis. DESIGN: A comparative study of cerebrovascular
      disease in patients dying of systemic lupus erythematosus (SLE) and the
      antiphospholipid syndrome. PATIENTS: Cerebrovascular disease observed in
      autopsies on a patient with primary antiphospholipid syndrome and a patient with
      SLE and antiphospholipid syndrome was compared with findings on two SLE patients
      who did not have serum antiphospholipid antibodies and with findings on 15
      patients having diseases in which pathological changes of meningeal arteries
      might be anticipated or are known to occur (six patients with hypertensive
      cerebrovascular disease, one patient with thrombotic thrombocytopenic purpura,
      seven patients with marantic or bacterial endocarditis, and one patient with a
      left ventricular mural thrombus). Multiple blocks of brain tissue were studied by
      serial histologic sections and histochemical and immunohistochemical methods.
      Immunofluorescent and electron microscopic (EM) studies were performed on kidneys
      and EM studies on brain and choroid plexus in each case of antiphospholipid
      syndrome. RESULTS: Leptomeningeal arteries of antiphospholipid syndrome patients
      disclosed fibrin thrombi and widespread obstruction by a proliferation of intimal
      fibrous tissue or myointimal cells. The fibrous and cellular segments of
      obstructed arteries frequently contained fibrin thrombi and displayed varying
      stages of recanalization. In late stages of organization, fibrous webs were
      formed across arterial lumens. Obstructed arteries were traced to small infarcts
      localized to an underlying column of cortical gray matter. None of the tissues
      from antiphospholipid syndrome patients showed evidence of an active or healed
      inflammatory vasculitis or of vascular immune complex deposits. Recanalized
      thrombi, fibrous and cellular occlusions, and fibrous webs were not found in the
      leptomeningeal arteries of patients who did not have the antiphospholipid
      syndrome. CONCLUSIONS: The cerebrovascular changes of the antiphospholipid
      syndrome are derived from a chronic thrombotic microangiopathy. The findings
      support the hypothesis that antiphospholipid antibodies can cause recurring
      episodes of intravascular thrombosis.

PMID- 8302807
TI  - Invasive micropapillary carcinoma of the breast.
AB  - Nine examples of a rare variant of invasive breast carcinoma characterized by the
      formation of micropapillae within clear spaces separated by a fibrocollagenous or
      delicate fibrovascular stroma are presented. Designated as invasive
      micropapillary carcinoma, the unusual morphology of this tumor requires its
      distinction from metastatic ovarian serous papillary carcinoma and extensive
      vascular/lymphatic invasion by either a primary or metastatic breast carcinoma.
      The micropapillary pattern is retained in metastatic foci and areas of
      recurrence. This pattern also occurs admixed with regular infiltrating duct
      carcinoma either in the primary mammary tumor or when it recurs.

PMID- 8302808
TI  - Detection of human papillomavirus DNA in oral verrucous carcinoma by polymerase
      chain reaction.
AB  - Archival tissue biopsies of 17 cases of oral verrucous carcinoma were tested for
      human papillomaviruses by polymerase chain reaction followed by DNA slot-blot
      hybridization. Sections of the biopsies were also tested by in situ DNA
      hybridization with biotin-labeled probes for human papillomavirus types 6/11,
      6/18, and 31/33/35. Using polymerase chain reaction, human papillomavirus DNA was
      detected in seven of 17 cases (41%). Slot-blot hybridization of the amplification
      products identified human papillomavirus type 6 in two cases, type 11 in four
      cases, and both types 6 and 11 in one case of oral verrucous carcinoma. In situ
      hybridization confirmed the presence of human papillomavirus type 6/11 DNA in
      tumor cell nuclei for each of the cases which tested positive by polymerase chain
      reaction and was negative in the remaining 10 cases. We conclude that human
      papillomavirus types 6 and 11 are frequently present in cases of oral verrucous
      carcinoma.

PMID- 8302809
TI  - Diabetic patients with IgA nephropathy and diabetic glomerulosclerosis.
AB  - Eleven diabetic patients with biopsy-proven IgA nephropathy were studied. Seven
      exhibited coexistence of both IgA nephropathy and diabetic glomerulosclerosis and
      the remaining four patients had IgA nephropathy without diabetic lesion. The
      clinicopathological features and follow-up of those patients with IgA nephropathy
      surperimposed on diabetic glomerulosclerosis were compared with a similar group
      of patients with diabetic glomerulosclerosis alone. Our observation suggests that
      the occurrence of both glomerulopathies was fortuitous with IgA nephropathy
      coexisting with or preceding diabetic glomerulosclerosis. There was no apparent
      causal relationship between the two glomerulopathies. The renal outcome is poor
      in both groups of patients and is possibly related to diabetic
      glomerulosclerosis.

PMID- 8302810
TI  - The significance of the grooved nucleus in thyroid lesions.
AB  - Nuclear grooving has recently been accepted as a useful diagnostic criterion for
      papillary thyroid carcinoma. In order to determine whether this feature can serve
      as a reliable cytomorphologic marker of papillary carcinoma we studied, by light
      microscope, the surgical specimens of 80 nonpapillary thyroid lesions including
      35 follicular adenomas, 8 follicular carcinomas, 5 Hurthle cell adenomas, 4
      Hurthle cell carcinomas, 4 medullary carcinomas, 2 undifferentiated carcinomas, 5
      cases of Hashimoto's thyroiditis, 5 diffuse hyperplasias, 2 adenomatous
      hyperplasias, and 10 nodular goiters. In each case, 10 random high-power fields
      (HPF) per slide were reviewed and the frequency of grooved nuclei per microscopic
      field examined and recorded. Nuclear grooves were found in all but 11 cases (one
      case of adenomatous hyperplasia and 10 cases of nodular goiter). Overall, 40% of
      the nonpapillary thyroid lesions contained nuclear grooves in more than 9 HPFs,
      42% in 5 to 8 HPFs and 18% in less than 4 HPFs. Twenty four percent of the
      nonpapillary neoplastic lesions had eight or more grooved nuclei per HPF and 76%
      had six or less. The latter frequency was recorded for the 50% of the
      nonneoplastic thyroid conditions. Occasional intranuclear inclusions were seen in
      two cases of follicular tumors and in one case of Hurthle cell carcinoma. It is
      apparent from this study that nuclear grooving is not necessarily restricted to
      papillary thyroid cancer, and that it can be present in a variety of other
      thyroid lesions.

PMID- 8302811
TI  - Marrow mast cell hyperplasia in hairy cell leukemia.
AB  - Marrow mast cells, frequently elevated in chronic B-lymphoproliferative
      disorders, were counted per high magnification field (HMF) on toluidine blue
      stained marrow biopsies from 34 patients diagnosed with hairy cell leukemia
      (HCL); similar counts were performed on splenic sections from nine of these
      patients. Biopsies from 28 normal marrow transplant donors and 10 normal spleens
      served as controls. Mast cells were distributed irregularly throughout normal and
      HCL marrows, but tended to be more concentrated about the hairy cells in cases
      focally involved by HCL. HCL marrows averaged 12.7 mast cells/HMF compared to 1.1
      for controls. Although most normal marrows (86%) averaged < 2 mast cells/HMF, 88%
      of HCL cases averaged > or = 2 mast cells/HMF. Splenic mast cells averaged <
      1/HMF for both HCL and control cases. By electron microscopy, marrow mast cells
      in HCL demonstrated normal substructure with numerous granules. The cell surfaces
      of mast cells showed filopodia that often came in contact with those of hairy
      cells. These results indicate most HCL marrows, but not spleens, are associated
      with varying degrees of mast cell hyperplasia. Furthermore, this study suggests a
      biologic interaction between mast cells and hairy cells. The significance of
      marrow mast cell hyperplasia in HCL is unknown, but these mast cells may
      contribute to the increased reticulin fiber network observed in HCL marrows.

PMID- 8302812
TI  - Hyperplasia of pulmonary arterial media in infantile familial pulmonary
      hypertension associated with severe metabolic acidosis.
AB  - Two female siblings, offspring of consanguinous parents, died at 10 and 12 wk of
      age following short illnesses characterized clinically by hypoxia and severe
      metabolic acidosis. Cardiac catheterization confirmed severe pulmonary
      hypertension in the second infant, who survived 6 wk after onset of symptoms and
      4 wk after admission to hospital; extensive investigations failed to identify any
      inborn metabolic error. At autopsy, small pulmonary arteries/arterioles in both
      cases showed marked medial thickening due to smooth muscle hyperplasia;
      concentric intimal fibrosis was present focally in the older infant. Compared
      morphometrically with small pulmonary arteries in 20 infantile controls who died
      of Reye's syndrome (n = 8), a Reye's-like illness (n = 5) or an identified
      metabolic error associated with metabolic acidosis (n = 7), intraacinar pulmonary
      arteries in both cases, were significantly more numerous and had a significantly
      greater relative medial thickness. We suggest that an autosomal recessive gene
      caused or potentiated the pulmonary medial hyperplasia. The latter finding,
      compared with medial hypertrophy, is rarely described as the morphologic basis of
      pulmonary hypertension, and its occurrence may be restricted to early infancy. In
      this family, the relationship between hypertensive pulmonary arteriopathy and
      severe metabolic acidosis remains speculative.

PMID- 8302813
TI  - Osteoblastoma-like osteosarcoma. The Rizzoli Institute experience.
AB  - A series of 11 osteosarcomas that histologically resembles osteoblastoma was
      reviewed. The ages of the seven males and four females ranged from 19 to 47 yr
      (average 29). In six patients the roentgenograms showed cortical destruction and
      poorly defined borders on the lesion; this roentgenographic presentation was
      suggestive of malignancy. Histologically, the tumor permeation of the surrounding
      host tissue allowed us to differentiate osteoblastoma-like osteosarcoma from
      osteoblastoma. The differential diagnosis can be very difficult or even
      impossible on a small biopsy. The first diagnosis was considered benign in nine
      of our cases. Osteoblastoma-like osteosarcoma is a rare variety of osteosarcoma
      (1.1% of all osteosarcoma). It is a low-grade malignant lesion in which
      recurrence is the rule when adequate surgical margins were not achieved (five
      patients). Two of these patients died from tumors after inadequate surgical
      treatment of the primary tumor as well as of the recurrences. The six patients
      who were treated with wide surgical margins were alive without recurrence. One of
      them had lung metastasis, twice, treated with wide-wedge resection. Osteoblastoma
      like osteosarcoma is a low-grade variety of osteosarcoma with characteristic
      histopathologic features. It needs to be recognized by the pathologist to achieve
      the right treatment which is wide surgical procedure.

PMID- 8302814
TI  - The occurrence of monocytoid B-lymphocytes in the spleen in gastric cancer.
AB  - Occurrence of monocytoid B-lymphocytes (MBL) in spleens of 34 patients with
      gastric cancer was examined. Histologic findings of gastric cancer including
      classification, depth of invasion, and stage of disease were defined based on the
      General Rules for the Gastric Cancer Study (Japan). MBL were defined
      morphologically as having abundant pale cytoplasm with distinct cell borders and
      small nucleus often with reniform shape. Immunohistochemically, these cells were
      B-cell in nature, i.e., CD15-, CD43-, CD45RA+, CD45Ro-, CD68-, CD74+, CDw75+, Mx
      PanB(L26)+, MBI+, EMA-, PG-MI-. Clusters of MBL were found in 14 of 34 (41%)
      patients: they were found to be directly adjoining to the periarterial sheath or
      apart from the white pulp. In the cases without MBL, zonation of mantle zone and
      marginal zone was apparent with distinct secondary follicles in 72% of cases.
      Meanwhile, in spleens with MBL, the mantle zone showed atrophy in a half of
      cases, resulting in indistinct zonation of the mantle zone and marginal zone.
      Secondary follicles were distinct in less than 30% of cases. Correlation of the
      occurrence of MBL, evaluated by Spearman's correlation coefficient, revealed that
      the age was the most important factor (R = -0.4852, P = 0.00364): the median age
      of patients with and without MBL was 75.7 and 61.7 yr, respectively. The MBL were
      increased in gastric cancer as compared with other cancers (P < 0.03) and with
      noncancer spleens (P < 0.1). The age of gastric cancer patients with MBL was
      older than those in other cancers and noncancer patients. Therefore occurrence of
      MBL in spleen might be a function of aging.

PMID- 8302815
TI  - Medullary carcinoma of the breast. Identification of lymphocyte subpopulations
      and their significance.
AB  - Fifty-two infiltrating breast carcinomas with medullary features (BCMF) were
      studied immunohistochemically to determine the immunophenotype of the mononuclear
      tumor inflammatory cells (MTIC) in formalin-fixed, paraffin-embedded material.
      The neoplasms were also examined for Epstein-Barr virus (EBV) DNA by the
      polymerase chain reaction (PCR). BCMF were independently classified as medullary
      carcinoma (MC) or infiltrating ductal carcinoma (IDC) by six observers according
      to the criteria of Pedersen et al. DNA from 35 BCMF was successfully amplified
      using PCR, but all were negative for EBV DNA. These included, by 4/6 consensus
      diagnosis, 16 MC, 18 IDC, and one BCMF which failed to achieve consensus
      diagnosis. MTIC were present to a mild degree in 19 BCMF (37%) and to moderate to
      severe degrees in 33 (63%). MTIC were predominantly (> or = 75%) lymphocytic in
      31 BCMF (13 MC, 16 IDC, two without consensus diagnostic agreement), and
      plasmacytic in 10 (six MC, four IDC); equal proportions of lymphocytes and plasma
      cells occurred in 11 (six MC, five IDC). Lymphocytic MTIC were mostly
      CD45RO+/CD3+ T-cells in nearly all cases, and showed a predominant CD3+/CD4+ and
      CD3+/CD4- immunophenotype in 36% and 64% of cases, respectively. Natural killer
      cells (CD57+) and histiocytes (MAC 387+) were virtually absent. The number, cell
      type, and T-cell subsets of the MTIC were unrelated to consensus diagnosis,
      axillary lymph node status, or overall survival. EBV is unassociated with MC,
      despite the histologic similarities of MC to EBV-associated lymphoepithelial
      lesions of other organs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8302816
TI  - Epstein-Barr virus distribution in nonneoplastic lymph nodes.
AB  - Epstein-Barr virus (EBV) has been associated with a wide variety of neoplastic
      conditions including nasopharyngeal carcinoma, gastric carcinoma,
      lymphoproliferative disorders in immunocompromised hosts, Hodgkin's disease, and
      non-Hodgkin's lymphomas of either B or T-cell phenotype. Although the presence of
      EBV in neoplastic lymph nodes has been well studied, very few studies have
      examined the distribution of EBV in normal or reactive lymph nodes. We studied
      normal or reactive lymph nodes from patients in Peru, a geographical region with
      a relatively high prevalence of EBV infection as compared with the United States
      or Europe. EBV DNA-RNA in situ hybridization was performed using a 30-base
      biotinylated oligonucleotide complementary to the EBER1 gene of EBV. Ten cases
      showed the presence of EBV RNA in scattered cells (less than 50 per section) and
      were utilized in the study. Most of the cells labeling for EBV RNA were small
      lymphocytes although some large lymphocytes also labeled. These cases were then
      subjected to double-labeling immunohistochemical/in situ hybridization studies
      using monoclonal antibodies L26(CD20), Leu22(CD43), Leu7(CD57), and the
      polyclonal antibody CD3. In their respective sections, of those cells that showed
      positive labeling for EBV RNA, 44% double labeled for L26, 24% double labeled for
      CD3, and 23% double labeled for Leu22. No cells double labeled for Leu7. This
      study shows that EBV RNA is expressed in both B and T-cells in nonneoplastic
      lymph nodes. These findings are compatible with other studies that have shown the
      presence of EBV in both B and T-cell non-Hodgkin's lymphomas.

PMID- 8302817
TI  - In consultation. Interstitial cystitis.

PMID- 8302818
TI  - The usefulness of the lactate dehydrogenase macroreaction in autopsy practice.
AB  - The detection of recent myocardial damage by means of the macroscopic lactate
      dehydrogenase reaction (LDHr) linked to nicotinamide adenine dinucleotide
      diaphorase (NADHd), conducted in a liquid medium is greatly insensitive to
      postmortal autolysis. In 10 heart cones (i.e., cardiac ventricles severed
      underneath the coronary sulcus) stored at 6 degrees C for up to 114 h after
      death, no autolytic artifacts appeared on freshly cut apical surfaces of
      transverse myocardial slices. In 10 cones kept at room temperature for up to 95 h
      after death, no artifacts appeared in eight cases; in two cases the LDHr was
      impaired by postmortal bacterial spread and decomposition of the myocardium.
      Intravital perfusion of injured myocardium increases the sensitivity of the LDHr.
      Postmortal stand-still of circulation is decisive in preserving dehydrogenase
      activities in undamaged myocardium. An artificial decrease in enzyme activity
      always appeared on the nonrecent, basally facing cut surfaces of slices exposed
      to air and fluid oozing out of the myocardium for long periods, even if the
      exposed surface of the cone was kept at 6 degrees C and wrapped in plastic. In
      normal practice, when bodies are stored in a refrigerating unit, the LDHr may
      still indicate myocardial damage more than 114 h after death.

PMID- 8302819
TI  - Metallothionein as an epithelial proliferative compartment marker for DNA flow
      cytometry.
AB  - The antibody to the metal-binding low molecular weight protein metallothionein
      (MT) stains preferentially the proliferative edge of epithelial tumors in
      paraffin sections. The present report demonstrates its usefulness as an
      epithelial cell marker in DNA flow cytometry of archival specimens. Nine control
      breast (mammoplasty) specimens, 10 control colonic specimens (resection edges),
      12 adenocarcinomas of breast, and 13 adenocarcinomas of colon were analyzed by
      DNA flow cytometry after MT and DNA staining. The average percentage of cells
      stained by MT ranged from 12% to 27% in these groups of specimens, which contain
      epithelial as well as stromal and inflammatory cells. Comparing cell turnover,
      measured as S-phase fraction (SPF) in unstained and MT-stained preparations, it
      was 10% and 20%, respectively, in control tissues and 10% and 30%, respectively,
      in adenocarcinomas. The SPF is lower in unstained preparations because of
      dilution by noncycling inflammatory and stromal cells. Immunohistochemical
      staining of various tissues for MT showed specific staining of epithelial cells.
      Evaluation of aneuploid malignant epithelial cells detected in six breast and
      eight colonic adenocarcinomas showed that on average, 47% of cells were stained
      with MT and that their SPF increased by about 50% when MT staining was compared
      with the unstained preparations. The results suggest that MT stains epithelial
      cells adequately for ploidy and cell cycle evaluation and that it may stain
      preferentially the proliferating cell compartment, which is considered to be an
      index of malignancy.

PMID- 8302820
TI  - Scanning electron microscopic distinction of pleural mesotheliomas from
      adenocarcinomas.
AB  - Cases of mesothelioma and adenocarcinoma involving pleura were examined by light
      and scanning electron microscopy utilizing H & E stained slides of paraffin
      embedded material. Areas of interest were identified and isolated, and the
      coverslips were removed. The slide fragments were mounted on scanning electron
      microscopy stubs and coated with gold for 45 sec. Cases were examined in a
      blinded manner. Microvilli were readily identified by scanning electron
      microscopy with preservation of morphologic detail through the processing and
      staining steps required for light microscopy. The length and diameter of 20
      microvilli were measured from each tumor. The mean length:diameter ratio for the
      mesotheliomas (n = 7) was 19.7:1 (range 13.7-23.5:1), and for the adenocarcinomas
      (n = 7), 2.5:1 (range 1.3-4.1) (P < 0.0005). Correlative transmission electron
      microscopy was performed on "scanned" specimens, and length:diameter ratios were
      generated. This technique has utility in distinguishing mesothelioma from
      adenocarcinoma. It is especially useful when glutaraldehyde-fixed, plastic
      embedded tissue is not available for transmission electron microscopy.
      Additionally, scanning electron microscopy allows more extensive examination than
      transmission electron microscopy and is far less limited by section thickness and
      tangential sectioning artifact.

PMID- 8302821
TI  - Administering the clinical laboratory: how directors relate to their laboratory
      innovators and managers.

PMID- 8302822
TI  - Multicentric Castleman's disease in a child with prominent thymic involvement: a
      case report and brief review of the literature.
AB  - A fatal case of multicentric Castleman's disease (giant lymph node hyperplasia)
      with prominent thymic involvement in a 12-yr-old girl is presented. Multicentric
      Castleman's disease is a poorly understood lymphoproliferative disorder generally
      occurring in elderly individuals. To our knowledge, this is the first case in the
      English literature of multicentric Castleman's disease in a child. Thymic
      involvement has not been described previously in the multicentric variant or in a
      child. Besides the characteristic findings of Castleman's disease (CD), such as
      hyaline-vascular follicles and a prominent plasmacytic infiltrate, the thymus was
      also marked by prominent epithelial hyperplasia in the medulla. The clinical and
      pathologic findings are presented with a review of the literature, particularly
      thymic involvement in CD and CD in the pediatric population.

PMID- 8302823
TI  - Perforation of the ileum secondary to Enterobius vermicularis report of a rare
      case.
AB  - An isolated ileal perforation is presented in a 12-yr-old patient. Microscopic
      examination revealed granulomatous inflammation due to Enterobius vermicularis
      (pinworm). This is only the third documented report of intestinal perforation
      involving pinworms. Although infestation with this parasite is generally
      considered to be relatively harmless, on rare occasions, it can be a significant
      cause of morbidity due to its potential ability to invade the tissues.

PMID- 8302824
TI  - Identification of the MAGE-1 gene product by monoclonal and polyclonal
      antibodies.
AB  - The human MAGE-1 gene encodes a melanoma peptide antigen recognized by autologous
      cytotoxic T lymphocytes. To produce antibodies against the MAGE-1 gene product,
      several approaches were taken. Three oligopeptides were synthesized based on
      predicted MAGE-1 amino acid sequences and were used to generate rabbit anti
      peptide anti-sera. In addition, a truncated MAGE-1 cDNA was cloned into an
      Escherichia coli expression vector, and recombinant protein was produced and
      purified. All three rabbit anti-peptide antisera showed reactivity against the
      immunizing peptide, and one reacted with the recombinant MAGE-1 protein by
      immunoblotting, but none reacted with cell lysates from MAGE-1 mRNA-positive
      cells. The recombinant MAGE-1 protein was then used for the generation of mouse
      monoclonal and rabbit polyclonal antibodies. One IgG1 monoclonal antibody, MA454,
      as well as rabbit polyclonal antisera recognized a 46-kDa protein in extracts of
      MAGE-1 mRNA-positive melanoma cell lines. The antibodies showed no apparent cross
      reactivity with products of the closely related MAGE-2 and MAGE-3 genes.
      Serological typing of normal and tumor cell lysates was in full agreement with
      mRNA analysis, showing expression of MAGE-1 protein in MAGE-1 mRNA-positive
      testis and a subset of melanomas but not in MAGE-1 mRNA-negative normal or tumor
      tissues. Transfection of the MAGE-1 gene into a MAGE-1 mRNA-negative melanoma
      cell line resulted in the expression of the 46-kDa protein, confirming the
      identity of this protein as the MAGE-1 gene product.

PMID- 8302825
TI  - Critical roles of the S3 segment and S3-S4 linker of repeat I in activation of L
      type calcium channels.
AB  - Each of the four repeats (or motifs) of voltage-gated ion channels is thought to
      contain six transmembrane segments (S1-S6). Mutational analyses indicate that S4
      functions as a voltage sensor and that the S5, S6, and S5-S6 linker contribute to
      formation of the ion pore. However, little information exists regarding the
      functional role(s) of the amino-terminal portion (S1-S3-S4 linker) of the
      repeats. Here we report that the amino acid composition of the S3 segment of
      repeat I and the linker connecting S3 and S4 segments of repeat I is critical for
      the difference in activation kinetics between cardiac and skeletal muscle L-type
      calcium channels. Mutant dihydropyridine receptors that have the skeletal muscle
      dihydropyridine receptor sequence in this region activated relatively slowly with
      the time constant of current activation (tau act) > 5 ms, whereas mutants that
      have the cardiac counterpart there activated relatively rapidly with tau act < 5
      ms. Comparison of these two mutant groups indicates that a total of 11
      conservative and 10 nonconservative amino acid changes from skeletal muscle to
      cardiac dihydropyridine receptor sequence are sufficient to convert activation
      from slow to fast. These data demonstrate a functional role for this region of
      voltage-gated ion channels.

PMID- 8302826
TI  - Effect of ethanol on cytochrome P450 in the rat brain.
AB  - After a single dose of ethanol (0.8 ml/kg) administered intraperitoneally, the
      P450 content of the rat brain increased from 62 +/- 19 to 230 +/- 97 pmol/g (wet
      weight) of tissue (mean +/- SD, n = 5). Most of this increase could be accounted
      for by a 10- to 20-fold increase in the olfactory lobes and hypothalamic preoptic
      area. The P450s were identified by Western blot analysis and by microsequencing
      of the N-terminal ends after resolution of the proteins on SDS gels. They were
      identified as P450 2C7, 2C11, 2E1, 4A3, 4A8, and a member of the P450 2D family.
      In P450 extracted from the brains of control rats, P450 2C and 4A were also
      detectable but at a much lower concentration. P450 1A1, 2A1, 2B1, or 3A was not
      detected in the brains of either control or ethanol-treated rats. Oral
      administration of the same dose of ethanol resulted in a similar increase in the
      whole brain but smaller effects in the olfactory lobes. This effect of ethanol on
      the P450 in the brain has implications for the mechanism of toxicity and the
      development of tolerance to ethanol and for the effects of other drugs and
      environmental pollutants that act on the central nervous system.

PMID- 8302828
TI  - Cellular epigenetics: control of the size, shape, and spatial distribution of
      transformed foci by interactions between the transformed and nontransformed
      cells.
AB  - NIH 3T3 cells that are passaged frequently at low density in high (10%) calf
      serum lose their original capacity to produce transformed foci on a monolayer of
      nontransformed cells. They can then be used to form a monolayered background for
      the assay of the number of focus-forming cells from a transformed population.
      Continuation of the low-density passages for many weeks gives rise to a
      population that can suppress the full development of foci by a transformed line.
      The suppression appears to occur only after the background cells have become
      confluent and contact inhibited. It can also cause the disappearance of light
      foci that had developed before suppression began. Another subline of cells that
      were passaged at cloning density only once a week lose their focus-forming
      capacity more slowly than those passaged thrice weekly. When used as a background
      for the assay of a transformed line, they permit continuous expansion of the
      foci, with no sign of suppression. Not only the number and size of foci but also
      their detailed morphology is influenced by the background on which they are
      formed. A suppressive background can also determine the spatial distribution of
      foci, presumably as a result of gradients in local cell density of the
      background. The permissiveness of a nontransformed cell population for focus
      formation by transformed cells appears to be related to the capacity of the
      nontransformed population itself to undergo transformation when exposed to the
      constraints used to induce transformation. These findings indicate there are many
      degrees of capacity to suppress focus formation and to overcome suppression. They
      have significance for tumor development and for the epigenetic interactions of
      normal development.

PMID- 8302827
TI  - All four known cyclic adducts formed in DNA by the vinyl chloride metabolite
      chloroacetaldehyde are released by a human DNA glycosylase.
AB  - We have previously reported that human cells and tissues contain a 1,N6
      ethenoadenine (epsilon A) binding protein, which, through glycosylase activity,
      releases both 3-methyladenine (m3A) and epsilon A from DNA treated with
      methylating agents or the vinyl chloride metabolite chloroacetaldehyde,
      respectively. We now find that both the partially purified human epsilon A
      binding protein and cell-free extracts containing the cloned human m3A-DNA
      glycosylase release all four cyclic etheno adducts--namely epsilon A, 3,N4
      ethenocytosine (epsilon C), N2,3-ethenoguanine (N2,3-epsilon G), and 1,N2
      ethenoguanine (1,N2-epsilon G). Base release was both time and protein
      concentration dependent. Both epsilon A and epsilon C were excised at similar
      rates, while 1,N2-epsilon G and N2,3-epsilon G were released much more slowly
      under identical conditions. The cleavage of glycosyl bonds of several
      heterocyclic adducts as well as those of simple methylated adducts by the same
      human glycosylase appears unusual in enzymology. This raises the question of how
      such a multiple, divergent activity evolved in humans and what may be its primary
      substrate.

PMID- 8302829
TI  - Superoxide and peroxynitrite in atherosclerosis.
AB  - The role of reactive oxygen species in the vascular pathology associated with
      atherosclerosis was examined by testing the hypothesis that impaired vascular
      reactivity results from the reaction of nitric oxide (.NO) with superoxide (O2-),
      yielding the oxidant peroxynitrite (ONOO-). Contractility studies were performed
      on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol
      feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired
      the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn
      superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to
      critical sites of .NO reaction with O2-. Intravenously injected liposomes (3000
      units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed
      group to a greater extent than in controls. Quantitative immunocytochemistry
      demonstrated enhanced distribution of SOD in both endothelial and vascular smooth
      muscle cells as well as in the extracellular matrix. SOD activity in vessel
      homogenates of liposome-treated rabbits was also increased. Incubation of beta
      very low density lipoprotein with ONOO- resulted in the rapid formation of
      conjugated dienes and thiobarbituric acid-reactive substances. Our results
      suggest that the reaction of O2- with .NO is involved in the development of
      atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation,
      as well as by limiting .NO stimulation of vascular smooth muscle guanylate
      cyclase activity.

PMID- 8302830
TI  - An analogue of the DnaJ molecular chaperone in Escherichia coli.
AB  - Escherichia coli DnaJ functions as a typical molecular chaperone in coordination
      with other heat shock proteins such as DnaK and GrpE in a variety of cellular
      processes. In this study, it was found that E. coli possesses an analogue of
      DnaJ, as judged from not only its primary structure but also its possible
      function. This protein, named CbpA (for curved DNA-binding protein), was first
      identified as a DNA-binding protein that preferentially recognizes a curved DNA
      sequence. Cloning and nucleotide sequencing of the gene encoding CbpA revealed
      that the predicted product is very similar to DnaJ in amino acid sequence:
      overall identity is 39%. The cbpA gene functions as a multicopy suppressor for
      dnaJ mutations. The mutational lesions characteristic of a dnaJ null mutant-
      namely, temperature sensitivity for growth and defects in lambda phage and mini-F
      DNA replication--were all restored upon introduction of the cbpA gene on a
      multicopy plasmid. An insertional mutant of cbpA was also isolated, which showed
      no noticeable phenotype, particularly with regard to temperature sensitivity for
      growth. However, when this cbpA::kan allele was combined with the dnaJ null
      allele, the resultant strain was unable to grow at 37 degrees C, at which strains
      carrying each mutation alone could grow normally. These genetic results are
      interpreted as meaning that the function(s) of CbpA in E. coli is closely related
      to that of DnaJ.

PMID- 8302831
TI  - Hidden Markov models of biological primary sequence information.
AB  - Hidden Markov model (HMM) techniques are used to model families of biological
      sequences. A smooth and convergent algorithm is introduced to iteratively adapt
      the transition and emission parameters of the models from the examples in a given
      family. The HMM approach is applied to three protein families: globins,
      immunoglobulins, and kinases. In all cases, the models derived capture the
      important statistical characteristics of the family and can be used for a number
      of tasks, including multiple alignments, motif detection, and classification. For
      K sequences of average length N, this approach yields an effective multiple
      alignment algorithm which requires O(KN2) operations, linear in the number of
      sequences.

PMID- 8302832
TI  - Distinct isoforms of neuregulin are expressed in mesenchymal and neuronal cells
      during mouse development.
AB  - Neuregulin, the putative ligand of the c-neu receptor tyrosine kinase, can induce
      differentiation or growth of epithelia and other cells. To gain insight into the
      biological role of this factor, we have analyzed the expression of neuregulin
      during mouse embryogenesis and in the perinatal animal by a combination of in
      situ hybridization and RNase protection experiments. We identify sites of
      expression that correspond to mesenchymal cells of various parenchymal organs.
      Our finding implies a function of neuregulin as a mesenchymal factor that acts on
      epithelia. The mesenchymal expression of neuregulin could thus provide a
      molecular basis for the biological phenomenon of mesenchymal-epithelial
      interactions. It also has implications on the molecular mechanism by which
      amplification of c-neu can affect tumor progression of carcinomas. In addition,
      neuregulin expression is found in neuronal cells during development. We show by
      RNase protection experiments that distinct isoforms of neuregulin are expressed
      in the brain. Therefore, our data indicate in vivo a dual role for neuregulin as
      mesenchymal and neuronal factor.

PMID- 8302833
TI  - Lysophosphatidylcholine upregulates the level of heparin-binding epidermal growth
      factor-like growth factor mRNA in human monocytes.
AB  - Lysophosphatidylcholine is increased in the plasma of hypercholesterolemic
      patients, is a component of oxidatively modified low-density lipoprotein, and, as
      such, may play an important role in atherosclerosis. Here we demonstrate that in
      human monocytes, lysophosphatidylcholine increases the level of mRNA encoding the
      heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent
      smooth muscle mitogen. Lysophosphatidylcholine treatment also enhances the
      release of heparin-binding mitogenic activity by these cells in culture. The anti
      inflammatory glucocorticoid dexamethasone inhibits the upregulation of HB-EGF
      mRNA induced by either lysophosphatidylcholine or bacterial lipopolysaccharide in
      cultured monocytes. However, the responses induced by lysophosphatidylcholine and
      by lipopolysaccharide differ in their kinetics. In addition, the response to
      lysophosphatidylcholine is resistant to the action of cycloheximide, whereas the
      response to lipopolysaccharide is not, suggesting that the activation mechanisms
      induced by these two stimuli are different. Since a nuclear run-on assay showed
      no effect of lysophosphatidylcholine on the transcription of the HB-EGF gene, we
      speculate that lysophosphatidylcholine may increase the level of HB-EGF mRNA by
      altering the processing or degradation of primary or mature transcripts.
      Lysophosphatidylcholine enhancement of monocyte production of HB-EGF may
      represent an important result of the interactions among oxidized low-density
      lipoprotein and monocyte-derived macrophages and may play a role in initiation of
      smooth muscle proliferation in atherogenesis.

PMID- 8302834
TI  - Keratinocyte growth factor functions in epithelial induction during seminal
      vesicle development.
AB  - Development of the seminal vesicle (SV) is elicited by androgens and is dependent
      on epithelial-mesenchymal interactions. Androgenic signal transmission from the
      androgen-receptor-positive mesenchyme to the epithelium has been postulated to
      involve paracrine factors. Keratinocyte growth factor (KGF), a member of the
      fibroblast growth factor family, is produced by stromal/mesenchymal cells and
      acts specifically on epithelial cells. The KGF transcript was detected by reverse
      transcription-polymerase chain reaction in newborn mouse SVs and by Northern blot
      analysis of RNA from cultured neonatal SV mesenchymal cells. Newborn SVs placed
      in organ culture undergo androgen-dependent growth and differentiation. Addition
      of a KGF-neutralizing monoclonal antibody to this system caused striking
      inhibition of both SV growth and branching morphogenesis. This inhibition was due
      to a decline in epithelial proliferation and differentiation, as the mesenchymal
      layer was not affected by anti-KGF treatment. When KGF (100 ng/ml) was
      substituted for testosterone in the culture medium, SV growth was approximately
      50% that observed with an optimal dose of testosterone (10(-7) M). All of these
      findings suggest that KGF is present during a time of active SV morphogenesis and
      functions as an important mediator of androgen-dependent development.

PMID- 8302835
TI  - Evolution of recombination among multiple selected loci: a generalized reduction
      principle.
AB  - Conditions for invasion by a new allele that controls the recombination pattern
      among an arbitrary number of genes under viability selection are studied. The
      recombination pattern may include interference. The new allele increases if its
      appropriately averaged marginal fitness is greater than the mean fitness prior to
      its introduction. Under weak additive-by-additive epistatic selection, this
      condition involves a weighted average of the changes in pairwise recombination
      rates relative to those prior to the introduction of the modifier. The weights
      here are positive functions of the epistatic selection components. In particular,
      the modifier allele may succeed even if it increases recombination among some
      pairs of loci, provided the overall average effect is one of reduction.

PMID- 8302836
TI  - Crystal structure of a disulfide-linked "trefoil" motif found in a large family
      of putative growth factors.
AB  - Porcine pancreatic spasmolytic polypeptide (PSP) belongs to a large family of
      homologous growth factor-like polypeptides characterized by a disulfide-linked
      "trefoil motif," duplicated and conserved in various family members. PSP contains
      two trefoil motifs, has several pharmacological actions on the gut, and has
      growth factor properties on epithelial cells in vitro. The human PSP analogue,
      human spasmolytic polypeptide, appears to be involved in many regenerative
      situations and, especially, in healing gastrointestinal ulcers. One member of the
      trefoil family, pS2, is secreted in approximately 50% of estrogen-dependent human
      breast carcinomas, which has led to its use as a tumor prognostic marker. Both
      pS2 and human spasmolytic polypeptide are also widely expressed in chronic
      gastrointestinal ulcerative conditions such as Crohn disease. Here we report the
      three-dimensional structure at 2.6-A resolution of a trefoil-containing protein,
      namely PSP, purified from porcine pancreas. The structure shows two homologous
      domains that share a supersecondary structure and disulfide bond pattern. The two
      domains pack asymmetrically giving rise to a number of protruding loops, exposed
      clefts, and an unusual electrostatic surface potential. Knowledge of the
      structure of PSP should allow the design of mutants to investigate further the
      function of PSP and other trefoil-containing peptides.

PMID- 8302837
TI  - Bound water molecules and conformational stabilization help mediate an antigen
      antibody association.
AB  - We report the three-dimensional structures, at 1.8-A resolution, of the Fv
      fragment of the anti-hen egg white lysozyme antibody D1.3 in its free and antigen
      bound forms. These structures reveal a role for solvent molecules in stabilizing
      the complex and provide a molecular basis for understanding the thermodynamic
      forces which drive the association reaction. Four water molecules are buried and
      others form a hydrogen-bonded network around the interface, bridging antigen and
      antibody. Comparison of the structures of free and bound Fv fragment of D1.3
      reveals that several of the ordered water molecules in the free antibody
      combining site are retained and that additional water molecules link antigen and
      antibody upon complex formation. This solvation of the complex should weaken the
      hydrophobic effect, and the resulting large number of solvent-mediated hydrogen
      bonds, in conjunction with direct protein-protein interactions, should generate a
      significant enthalpic component. Furthermore, a stabilization of the relative
      mobilities of the antibody heavy- and light-chain variable domains and of that of
      the third complementarity-determining loop of the heavy chain seen in the complex
      should generate a negative entropic contribution opposing the enthalpic and the
      hydrophobic (solvent entropy) effects. This structural analysis is consistent
      with measurements of enthalpy and entropy changes by titration calorimetry, which
      show that enthalpy drives the antigen-antibody reaction. Thus, the main forces
      stabilizing the complex arise from antigen-antibody hydrogen bonding, van der
      Waals interactions, enthalpy of hydration, and conformational stabilization
      rather than solvent entropy (hydrophobic) effects.

PMID- 8302838
TI  - Identification of T-cell receptor alpha-chain genes in the chicken.
AB  - T-cell receptor (TCR) alpha-chain (TCR alpha) and beta-chain (TCR beta) genes are
      well characterized in mammals, while only TCR beta genes have been identified in
      other vertebrates. To identify avian TCR alpha genes, we used monoclonal anti-CD3
      antibodies to isolate chicken TCR alpha for peptide sequence analysis. Degenerate
      oligonucleotide probes were then used to isolate a candidate TCR alpha cDNA clone
      that hybridized with a 1.7-kb mRNA species present only in alpha beta T cells and
      in tissues populated by these cells. Southern blot analysis revealed gene
      rearrangement in thymocytes and alpha beta T-cell lines. The TCR alpha cDNA
      candidate encoded an open reading frame of 275 amino acids, the predicted
      variable (V)-, joining (J)-, and constant (C)-region amino acid sequences of
      which shared approximately 40%, 60%, and 25% homology with corresponding
      mammalian sequences. A single C alpha gene and approximately 25 V alpha genes
      were identified by using region-specific probes. The V alpha cDNA probe isolated
      from a V beta 1+ cell line reacted with transcripts from one of five V beta 2+
      cell lines, suggesting shared use of V alpha genes by V beta 1+ and V beta 2+ T
      cells and the existence of other V alpha gene families. A genomic V alpha
      sequence was flanked by classical recombination signal sequences but, unlike
      previously defined V genes, the leader and V alpha region were encoded by a
      single exon. The data indicate evolutionary conservation of the basic TCR alpha
      gene structure in birds and mammals.

PMID- 8302839
TI  - Stimulation of endogenous ADP-ribosylation by brefeldin A.
AB  - Brefeldin A (BFA) is a fungal metabolite that exerts profound and generally
      inhibitory actions on membrane transport. At least some of the BFA effects are
      due to inhibition of the GDP-GTP exchange on the ADP-ribosylation factor (ARF)
      catalyzed by membrane protein(s). ARF activation is likely to be a key event in
      the association of non-clathrin coat components, including ARF itself, onto
      transport organelles. ARF, in addition to participating in membrane transport, is
      known to function as a cofactor in the enzymatic activity of cholera toxin, a
      bacterial ADP-ribosyltransferase. In this study we have examined whether BFA, in
      addition to inhibiting membrane transport, might affect endogenous ADP
      ribosylation in eukaryotic cells. Two cytosolic proteins of 38 and 50 kDa were
      enzymatically ADP-ribosylated in the presence of BFA in cellular extracts. The 38
      kDa substrate was tentatively identified as the glycolytic enzyme glyceraldehyde
      3-phosphate dehydrogenase. The BFA-binding components mediating inhibition of
      membrane traffic and stimulation of ADP-ribosylation appear to have the same
      ligand specificity. These data demonstrate the existence of a BFA-sensitive
      mono(ADP-ribosyl)transferase that may play a role in membrane movements.

PMID- 8302840
TI  - Proliferative responses and binding properties of hematopoietic cells transfected
      with low-affinity receptors for leukemia inhibitory factor, oncostatin M, and
      ciliary neurotrophic factor.
AB  - Specific low-affinity receptors for leukemia inhibitory factor (LIF), oncostatin
      M (OSM; gp130), and ciliary neurotrophic factor (CNTF; receptor alpha, CNTFR
      alpha) may be utilized in various combinations to generate high-affinity binding
      sites and signal transduction. We have tested the ability of combinations of
      these receptors to transduce a proliferative signal in BAF-B03 cells.
      Coexpression of the LIF receptor and gp130 in these cells conferred high-affinity
      LIF and OSM binding and responsiveness to LIF and OSM. These cells also responded
      to CNTF in the absence of detectable binding. The further addition of CNTFR alpha
      conferred high-affinity CNTF binding and enhanced responsiveness to CNTF but did
      not modify responses to LIF or OSM. Coexpression of LIF receptor and CNTFR alpha
      resulted in a nonfunctional high-affinity binding site. These data are consistent
      with a role for the CNTFR alpha in enhancing CNTF action but the CNTFR alpha is
      not absolutely required for CNTF action and suggest a wider range of targets for
      CNTF.

PMID- 8302841
TI  - Phylogenetic subtypes of human T-lymphotropic virus type I and their relations to
      the anthropological background.
AB  - Isolates of human T-lymphotropic virus type I (HTLV-I) were phylogenetically
      analyzed from native inhabitants in India and South America (Colombia and Chile)
      and from Ainu (regarded as pure Japanese descendants from the preagricultural
      "Jomon" period). Their genomes were partially sequenced together with isolates
      from Gabon in central Africa and from Ghana in West Africa. The phylogenetic tree
      was constructed from the sequence data obtained and those of previously reported
      HTLV-I isolates and simian T-lymphotropic virus type I (STLV-I) isolates. The
      heterogeneity of HTLV-I was recently recognized, and one major type, generally
      called the "cosmopolitan" type, contained Japanese, Caribbean, and West African
      isolates. The phylogenetic tree constructed in the present study has shown that
      this cosmopolitan type can be further grouped into three lineages (subtypes A, B,
      and C). Subtype A consists of some Caribbean, two South American, and some
      Japanese isolates, including that from the Ainu, in addition to an Indian
      isolate, and subtype B consists of other Japanese isolates in addition to another
      Indian isolate, suggesting that there might be at least two ancestral lineages of
      the Japanese HTLV-I. Subtype A implies a close connection of the Caribbean and
      South American natives with the Japanese and thereby a possible migration of the
      lineage to the American continent via Beringia in the Paleolithic era. Subtype C
      consists of the West African and other Caribbean isolates, indicating that not
      all but part of the Caribbean strains directly originated from West Africa
      probably during the period of slave trade. The tree also has shown that the HTLV
      I isolate from Gabon in central Africa forms a cluster with STLV-I from a
      chimpanzee, suggesting a possible interspecies transmission between man and the
      chimpanzee in the past. No specific clustering was observed in the tree in
      relation to manifestations of the disease such as adult T-cell leukemia and HTLV
      I-related neurological disorders. Thus, the topology of the phylogenetic tree
      reflects the movement of people carrying the virus in the past.

PMID- 8302842
TI  - Intracellular pH and the control of multidrug resistance.
AB  - Many anticancer drugs are classified as either weak bases or molecules whose
      binding to cellular structures is pH dependent. Accumulation of these drugs
      within tumor cells should be affected by transmembrane pH gradients. Indeed,
      development of multidrug resistance (MDR) in tumor cells has been correlated with
      an alkaline shift of cytosolic pH. To examine the role of pH in drug
      partitioning, the distribution of two drugs, doxorubicin and daunomycin, was
      monitored in fibroblasts and myeloma cells. In both cell types the drugs rapidly
      accumulated within the cells. The highest concentrations were measured in the
      most acidic compartments--e.g., lysosomes. Modifying the cellular pH in drug
      sensitive cells to mimic reported shifts in MDR caused an immediate change in the
      cellular drug concentration. Drug accumulation was enhanced by acidic shifts and
      reversed by alkaline shifts. All of these effects were rapid and reversible.
      These results demonstrate that the alkaline shift observed in MDR is sufficient
      to prevent the accumulation of chemotherapeutic drugs independent of active drug
      efflux.

PMID- 8302843
TI  - Exogenous Mtv-7 superantigen transgene expression in major histocompatibility
      complex class II I-E- mice reconstituted with embryonic stem cell-derived
      hematopoietic stem cells.
AB  - Direct genetic manipulation of hematopoietic cells is limited by the lack of an
      established hematopoietic stem cell line. It has been demonstrated that embryonic
      stem (ES) cell<-->tetraploid embryos are completely ES cell-derived and that
      fetal liver (FL) cells from these embryos support hematopoiesis in lethally
      irradiated recipients. In this report, we demonstrate that FL cells from ES cell<
      ->tetraploid embryos support normal lymphopoiesis and T-cell repertoire
      development. Moreover, the introduction of the Mtv-7 superantigen transgene
      coding for minor lymphocyte stimulatory antigen 1 into murine hematopoietic cells
      via reconstitution with ES cell<-->tetraploid FL cells demonstrates that this
      method can effectively confer stable genetic changes into the hematopoietic
      tissues without going through the germ line. Long-term and secondary
      reconstitution with ES cell<-->tetraploid FL cells expressing the Mtv-7
      superantigen transgene clonally deleted minor lymphocyte stimulatory antigen 1
      reactive T-cell receptor V beta 6+, -8.1+, and -9+ T cells, but not V beta 7+ T
      cells, in H-2b (I-E-) mice. This model system will be extremely important for
      analyzing structure-function relationships of molecules involved in
      proliferation, differentiation, and selection of hematopoietic cells in vivo and
      for examining hematopoiesis-specific effects of mutations that are lethal during
      embryogenesis.

PMID- 8302844
TI  - Selection for mefloquine resistance in Plasmodium falciparum is linked to
      amplification of the pfmdr1 gene and cross-resistance to halofantrine and
      quinine.
AB  - Two chloroquine-resistant cloned isolates of Plasmodium falciparum were subjected
      to mefloquine selection to test if this resulted in alterations in chloroquine
      sensitivity and amplification of the pfmdr1 gene. The mefloquine-resistant lines
      derived by this selection were shown to have amplified and overexpressed the
      pfmdr1 gene and its protein product (Pgh1). Macrorestriction maps of chromosome
      5, where pfmdr1 is encoded, showed that this chromosome has increased in size in
      response to mefloquine selection, indicating the presence of a gene(s) in this
      area of the genome that confers a selective advantage in the presence of
      mefloquine. Concomitant with the increase in mefloquine resistance was a
      corresponding increase in the level of resistance to halofantrine and quinine,
      suggesting a true multidrug-resistance phenotype. The mefloquine-selected
      parasite lines also showed an inverse relationship between the level of
      chloroquine resistance and increased pfmdr1 gene copy number. These results have
      important implications for the derivation of amplified copies of the pfmdr1 gene
      in field isolates, as they suggest that quinine pressure may be involved.

PMID- 8302845
TI  - Intra- and extracellular calcium modulates stereocilia stiffness on chick
      cochlear hair cells.
AB  - Segments of the chick basilar papilla were isolated and maintained in culture
      medium. The sensory hair bundle of individual hair cells was observed with light
      microscopy and stimulated with a water microjet at 600 Hz. Hair bundle motion was
      slowed by illuminating the microscope with stroboscopic light, and water jet
      intensity was systematically varied in decibel (dB) steps until a visual
      detection level (VDL) threshold of hair bundle motion was achieved. The VDL
      threshold of many hair cells was measured in each isolated papilla. However, only
      one of eight extracellular calcium concentrations (0.0, 0.0001, 0.001, 0.01, 0.1,
      1.25, 6.0, and 12.0 mM) was used with each papilla. In a second series, a calcium
      ionophore (ionomycin) was added to the culture medium, and VDL thresholds were
      again measured at seven of these extracellular calcium concentrations. With
      extracellular calcium alone, the stimulus level needed to achieve threshold was
      reduced by 2.73 dB between 0.1 and 0.01 mM. This change in threshold represented
      a 1.37-fold decrease in hair bundle stiffness. When ionomycin was added to the
      culture medium, a progressively greater stimulus intensity was needed to achieve
      threshold as calcium concentration increased. The 11.7-dB increase in threshold,
      with the addition of ionomycin, between 0.0001 and 6.0 mM extracellular calcium
      was equivalent to a 3.85-fold increase in bundle stiffness. These large changes
      in hair-bundle stiffness, as a function of the extra- or intracellular calcium
      environment, may play an important role in the micromechanical behavior of the
      hair cell during sound simulation.

PMID- 8302846
TI  - Mitochondrial DNA "clock" for the Amerinds and its implications for timing their
      entry into North America.
AB  - Students of the time of entry of the ancestors of the Amerinds into the New World
      are divided into two camps, one favoring an "early" entry [more than
      approximately 30,000 years before the present (YBP)], the other favoring a "late"
      entry (less than approximately 13,000 YBP). An "intermediate" date is unlikely
      for geological reasons. The correlation of the appropriate data on mtDNA
      variation in Amerinds with linguistic, archaeological, and genetic data offers
      the possibility of establishing a time frame for mtDNA evolution in Amerinds. In
      this paper, we estimate that the separation of the Chibcha-speaking tribes of
      Central America from other linguistic groups/nascent tribes began approximately
      8000-10,000 YBP. Characterization of the mtDNA of 110 Chibcha speakers with 14
      restriction enzymes leads on the basis of their time depth to an estimated mtDNA
      nucleotide substitution rate for Amerinds of 0.022-0.029% per 10,000 years. As a
      first application of this rate, we consider the mtDNA variation observed in 18
      Amerind tribes widely dispersed throughout the Americas and studied by ourselves
      with the same techniques, and we estimate that if the Amerinds entered the New
      World as a single group, that entry occurred approximately 22,000-29,000 YBP.
      This estimate carries a large but indeterminate error. The mtDNA data are thus at
      present equivocal with respect to the most likely times of entry of the Amerind
      into the New World mentioned above but favor the "early" entry hypothesis.

PMID- 8302847
TI  - Autophosphorylation and phosphotransfer in the Bordetella pertussis BvgAS signal
      transduction cascade.
AB  - Expression of adhesins, toxins, and other virulence factors of Bordetella
      pertussis is under control of the BvgA and BvgS proteins, members of a bacterial
      two-component signal transduction family. BvgA bears sequence similarity to
      regulator components, whereas BvgS shows similarity to both sensor and regulator
      components. BvgA and the cytoplasmic portion of BvgS ('BvgS) were overexpressed
      and purified. 'BvgS autophosphorylated with the gamma-phosphate from [gamma
      32P]ATP and phosphorylated BvgA. Kinetic analysis indicated that BvgA receives
      its phosphate from 'BvgS. Mutations in the transmitter, receiver, and C-terminal
      domains of BvgS were tested for activation of a BvgAS-dependent fhaB::lacZ
      reporter fusion in vivo and for autophosphorylation and phosphotransfer to BvgA
      in vitro. All mutations abolished activation of the fhaB::lacZ fusion. A point
      mutation in the transmitter (H729Q) prevented autophosphorylation of 'BvgS. In
      contrast to other characterized sensor proteins, autophosphorylation also
      required sequences in the 'BvgS receiver and C-terminal domains. A 'BvgS receiver
      point mutation (D1023N) had the novel phenotype of being able to
      autophosphorylate but unable to transfer the phosphate to BvgA.
      Autophosphorylation activity of the D1023N mutant protein was kinetically and
      chemically indistinguishable from wild-type 'BvgS despite an uncoupling of
      phosphotransfer from autophosphorylation. 'BvgS was shown to contain primarily
      amidyl phosphate and BvgA an acyl phosphate linkage. We present a model for a
      phosphorelay controlling virulence gene expression in B. pertussis.

PMID- 8302848
TI  - A human amphotropic retrovirus receptor is a second member of the gibbon ape
      leukemia virus receptor family.
AB  - Retrovirus infection is initiated by binding of the viral envelope glycoprotein
      to a cell-surface receptor. The envelope proteins of type C retroviruses of
      mammals demonstrate similarities in structural organization and protein sequence.
      These similarities suggest the possibility that retroviruses from different
      interference groups might use related proteins as receptors, despite the absence
      of any relationship between retrovirus receptors isolated to date. To investigate
      this possibility, we have identified a human cDNA clone encoding a protein
      closely related to the receptor for gibbon ape leukemia virus and have found that
      it functions as the receptor for the amphotropic group of murine retroviruses.
      Expression of this protein (GLVR-2) is likely to be a requirement for infection
      of human cells by amphotropic retroviral vectors for purposes of gene therapy.

PMID- 8302849
TI  - DNA double-strand break repair: genetic determinants of flanking crossing-over.
AB  - Whether or not homologous interaction of two DNA molecules results in crossing
      over of the flanking sequences is an important decision in view of genome
      organization. Several homologous recombination models, including the double
      strand break repair models, explain this decision as choice between two
      alternative modes of resolution of Holliday-type intermediates. We have
      demonstrated that a double-strand gap can be repaired through gene conversion
      copying a homologous duplex, as predicted by the double-strand break repair
      models, in the RecE pathway of Escherichia coli. This gap repair is often
      accompanied by crossing-over of the flanking sequences. Mutations in ruvC and
      recG, whose products interact with Holliday structures in vitro, do not block
      double-strand gap repair or its association with flanking crossing-over. However,
      two mutations in the recJ gene, which encodes a single-strand 5'-->3'
      exonuclease, severely decrease association of flanking crossing-over. Two
      mutations in the recQ gene, which encodes a helicase, moderately decrease
      association of flanking crossing-over by themselves and suppress the severe
      effect of a recJ mutation. Similar relationships of recJ and recQ mutations are
      observed in cell survival after ultraviolet light irradiation, gamma-ray
      irradiation, and H2O2 treatment. We discuss how cooperation of the recQ gene
      product and the recJ gene product brings about double-strand break repair
      accompanied by flanking crossing-over. We also discuss how this reaction is
      related to repair of chromosome damages.

PMID- 8302850
TI  - PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21)
      translocation in acute promyelocytic leukemia inhibit ligand-dependent
      transactivation of wild-type retinoic acid receptors.
AB  - Recently, we described a recurrent variant translocation, t(11;17)(q23;q21), in
      acute promyelocytic leukemia (APL) which juxtaposes PLZF, a gene encoding a zinc
      finger protein, to RARA, encoding retinoic acid receptor alpha (RAR alpha). We
      have now cloned cDNAs encoding PLZF-RAR alpha chimeric proteins and studied their
      transactivating activities. In transient-expression assays, both the PLZF(A)-RAR
      alpha and PLZF(B)-RAR alpha fusion proteins like the PML-RAR alpha protein
      resulting from the well-known t(15;17) translocation in APL, antagonized
      endogenous and transfected wild-type RAR alpha in the presence of retinoic acid.
      Cotransfection assays showed that a significant repression of RAR alpha
      transactivation activity was obtained even with a very low PLZF-RAR alpha
      expressing plasmid concentration. A "dominant negative" effect was observed when
      PLZF-RAR alpha fusion proteins were cotransfected with vectors expressing RAR
      alpha and retinoid X receptor alpha (RXR alpha). These abnormal transactivation
      properties observed in retinoic acid-sensitive myeloid cells strongly implicate
      the PLZF-RAR alpha fusion proteins in the molecular pathogenesis of APL.

PMID- 8302851
TI  - Oxidative susceptibility of low density lipoprotein subfractions is related to
      their ubiquinol-10 and alpha-tocopherol content.
AB  - The conjugated polyene fatty acid parinaric acid (PnA) undergoes a stoichiometric
      loss in fluorescence upon oxidation and can be used to directly monitor
      peroxidative stress within lipid environments. We evaluated the course of
      potentially atherogenic oxidative changes in low density lipoproteins (LDL) by
      monitoring the oxidation of PnA following its incorporation into buoyant (p =
      1.026-1.032 g/ml) and dense (p = 1.040-1.054 g/ml) LDL subfractions. Copper
      induced oxidation of LDL-associated PnA exhibited an initial lag phase followed
      by an increased rate of loss until depletion. Increased PnA oxidation occurred
      immediately after the antioxidants ubiquinol-10 and alpha-tocopherol were
      consumed but before there were marked elevations in conjugated dienes. Despite
      differences in sensitivity to early oxidation events, PnA oxidation and
      conjugated diene lag times were correlated (r = 0.582; P = 0.03), and both
      indicated a greater susceptibility of dense than buoyant LDL in accordance with
      previous reports. The greater susceptibility of PnA in dense LDL was attributed
      to reduced levels of ubiquinol-10 and alpha-tocopherol, which were approximately
      50% lower than in buoyant LDL (mol of antioxidant/mol of LDL) and together
      accounted for 80% of the variation in PnA oxidation lag times. These results
      suggest that PnA is a useful probe of LDL oxidative susceptibility and may be
      superior to conjugated dienes for monitoring the initial stages of LDL lipid
      peroxidation. Differences in oxidative susceptibility among LDL density
      subfractions are detected by the PnA assay and are due in large part to
      differences in their antioxidant content.

PMID- 8302852
TI  - A cocaine-sensitive Drosophila serotonin transporter: cloning, expression, and
      electrophysiological characterization.
AB  - A cocaine-sensitive, high-affinity Drosophila serotonin (5-hydroxytryptamine;
      5HT) transporter cDNA, denoted dSERT1, was isolated and characterized in oocytes.
      dSERT1 shows little transport of other monoamines and is Na+ and Cl- dependent.
      Sequence analysis indicates 12 putative transmembrane domains and strong
      homologies (approximately 50%) among dSERT1 and mammalian 5HT, norepinephrine,
      and dopamine transporters. Interestingly, the pharmacological properties of
      dSERT1, including sensitivity to antidepressants, are more similar to those of
      mammalian catecholamine transporters than to mammalian 5HT transporters. Two
      electrode voltage-clamp analysis demonstrated 5HT-induced, voltage-dependent
      currents. Cloning and characterization of dSERT1 adds significantly to our
      knowledge of the diversity of 5HT transporters with regard to primary sequence,
      pharmacological profile, and permeation properties.

PMID- 8302853
TI  - The delta-opioid receptor: isolation of a cDNA by expression cloning and
      pharmacological characterization.

PMID- 8302854
TI  - Cloning of an intracellular receptor for protein kinase C: a homolog of the beta
      subunit of G proteins.
AB  - Protein kinase C (PKC) translocates from the soluble to the cell particulate
      fraction on activation. Intracellular receptors that bind activated PKC in the
      particulate fraction have been implicated by a number of studies. Previous work
      identified 30- to 36-kDa proteins in the particulate fraction of heart and brain
      that bound activated PKC in a specific and saturable manner. These proteins were
      termed receptors for activated C-kinase, or RACKs. In the following study, we
      describe the cloning of a cDNA encoding a 36-kDa protein (RACK1) that fulfills
      the criteria for RACKs. (i) RACK1 bound PKC in the presence of PKC activators,
      but not in their absence. (ii) PKC binding to the recombinant RACK1 was not
      inhibited by a pseudosubstrate peptide or by a substrate peptide derived from the
      pseudosubstrate sequence, indicating that the binding did not reflect simply PKC
      association with its substrate. (iii) Binding of PKC to RACK1 was saturable and
      specific; two other protein kinases did not bind to RACK1. (iv) RACK1 contains
      two short sequences homologous to a PKC binding sequence previously identified in
      annexin I and in the brain PKC inhibitor KCIP. Peptides derived from these
      sequences inhibited PKC binding to RACK1. Finally, RACK1 is a homolog of the beta
      subunit of G proteins, which were recently implicated in membrane anchorage of
      the beta-adrenergic receptor kinase [Pitcher, J., Inglese, L., Higgins, J. B.,
      Arriza, J. A., Casey, P. J., Kim, C., Benovic, J. L., Kwatra, M. M., Caron, M. G.
      & Lefkowitz, R. J. (1992) Science 257, 1264-1267]. Our in vitro data suggest a
      role for RACK1 in PKC-mediated signaling.

PMID- 8302855
TI  - Identification of active-site residues of the adenovirus endopeptidase.
AB  - Multiple sequence alignment of the 12 adenovirus endopeptidases known to date
      identified a number of conserved residues which might be important for enzyme
      activity. Eleven mutants were created in the cloned gene by site-directed
      mutagenesis to identify the active site of this thiol endopeptidase. Analysis of
      the proteolytic activity in a crude system using viral precursor proteins, as
      well as in a purified system with activated proteinases using a new chromophoric
      octapeptide substrate, yielded results consistent with Cys-104 and His-54 being
      two members of the active site. This result was confirmed by the
      carboxymethylation of the reactive Cys-104 and its prevention by the active-thiol
      specific agent E64. Although Cys-122 and Cys-126 were also reactive cysteines,
      mutation of these residues did not affect enzyme activity. Replacement of the
      active-site Cys-104 by serine converted the enzyme into a serine-like proteinase,
      sensitive to serine proteinase inhibitors. The absence of homology to other
      proteinases, particularly at the active-site cysteine, coupled with the
      requirement for activation by a substrate cleavage fragment, indicates that the
      adenovirus endoproteinase may represent a new subclass of cysteine proteinases.

PMID- 8302856
TI  - Liver fatty acid-binding protein: specific mediator of the mitogenesis induced by
      two classes of carcinogenic peroxisome proliferators.
AB  - Peroxisome proliferators (PP) are a diverse group of chemicals that induce
      dramatic increases in peroxisomes in rodent hepatocytes, followed by hypertrophy,
      hepatomegaly, alterations in lipid metabolism, mitogenesis, and finally
      hepatocarcinomas. Termed nongenotoxic carcinogens, they do not interact with DNA,
      are not mutagenic in bacterial assays, and fail to elicit many of the phenotypes
      associated with classic genotoxic carcinogens. We report here that the
      mitogenesis induced by the major PP class, the amphipathic carboxylates, and by
      the tetrazole-substituted acetophenones specifically requires liver fatty acid
      binding protein (L-FABP) in cultured rat hepatoma cells transfected with the
      sense cDNA of L-FABP, in contrast to L-FABP-nonexpressing cells transfected with
      its antisense cDNA. The mitogenic actions of L-FABP were protein-specific,
      inasmuch as no other protein in the nonexpressing cells could act like L-FABP. L
      FABP was previously shown not only (i) to interact covalently with metabolites of
      the two genotoxic carcinogens 2-acetylaminofluorene and aminoazo dyes during
      liver carcinogenesis, but also (ii) to bind noncovalently the two classes of PP
      in vitro with avidities that correlate with their abilities to elicit peroxisomal
      enzymatic responses, and (iii) together with unsaturated fatty acids, especially
      linoleic acid, to promote multiplication of the transfected hepatoma cells in
      culture. The convergence of the two types of genotoxic carcinogens with the two
      classes of PP nongenotoxic carcinogens, and also with unsaturated fatty acids, at
      L-FABP actions in inducing mitogenesis allows the following hypothesis. During
      tumor promotion of carcinogenesis in vivo, these groups of genotoxic and
      nongenotoxic carcinogens act on the normal process by which L-FABP, functioning
      as a specific receptor of unsaturated fatty acids or their metabolites, promotes
      hepatocyte proliferation.

PMID- 8302857
TI  - Association of a cellular myosin II with anionic phospholipids and the neuronal
      plasma membrane.
AB  - Myosin II has been observed in close proximity to the neuronal plasma membrane,
      suggesting the possibility that at least one isoform of neuronal myosin II may be
      capable of direct association. Here, we demonstrate that a significant fraction
      (> 30%, saturable around 90%) of brain myosin II, but not myosins from skeletal
      or cardiac muscle, can bind to lipid vesicles composed of the anionic
      phospholipid L-alpha-phosphatidyl-L-serine but not with vesicles made from the
      neutral phospholipid L-alpha-phosphatidylcholine. Binding to lipid vesicles made
      from L-alpha-phosphatidyl-L-serine is enhanced in the presence of millimolar
      amounts of free calcium. ATPase activity remains unimpaired after vesicle
      association. Myosin II was also shown to remain in tight association with
      purified plasma membranes, even after depletion of actin. The above observations
      suggest that mechanisms involving membrane-bound myosin II are required to
      facilitate metazoan cell motility.

PMID- 8302858
TI  - DNA class organization on maize Adh1 yeast artificial chromosomes.
AB  - The organization of higher plant genomes is poorly understood. These genomes are
      typified by their large size and extensive repetitive DNA component. To further
      our understanding of the composition and arrangement of genomic DNA sequences, we
      have performed a detailed analysis of a contiguous interval of 280 kb surrounding
      the Adh1 locus of maize. A series of overlapping lambda subclones was isolated,
      and individual fragments were characterized with respect to their genomic copy
      number. Cross-hybridization analyses were used to define a minimum of 37
      repetitive DNA classes within the 280-kb interval. Hybridizations with highly
      repetitive DNAs cloned from other regions of the maize genome suggested that >
      50% of all highly repetitive elements in maize are represented on this single
      yeast artificial chromosome. These repeated sequences were found in an
      organizational pattern not previously observed; individual repetitive elements
      are interspersed with one another in an apparently random fashion and are
      spatially separate from single copy number sequences. Extensive tandem arrays
      were not found. Sequences from one end of the 280-kb interval were used to
      isolate overlapping yeast artificial chromosome clones, representing the first
      step in a chromosome walk.

PMID- 8302859
TI  - Molecular cloning and expression of the Saccharomyces cerevisiae RFC3 gene, an
      essential component of replication factor C.
AB  - Yeast replication factor C (RF-C) is a multi-polypeptide complex required for
      processive DNA replication by DNA polymerases delta and epsilon. The gene
      encoding the 40-kDa subunit of the Saccharomyces cerevisiae RF-C (RFC3) has been
      cloned. The RFC3 gene is required for yeast cell growth and has been mapped to
      the left arm of chromosome XIV. The deduced amino acid sequence of the RFC3 gene
      shows a high homology to the 36-, 37-, and 40-kDa subunits of human RF-C (also
      called activator 1), with the highest homology to the 36-kDa subunit. Among the
      conserved regions are the A motif of ATP binding proteins; the "DEAD box," common
      to DNA helicases and other ATPases; and the "RFC box," an approximately 15-amino
      acid domain virtually identical in the yeast and human RF-C subunits. Limited
      homology to the functional homologs of the Escherichia coli replication apparatus
      was also observed. The steady-state mRNA levels of RFC3 do not change
      significantly during the mitotic cell cycle of yeast. The intact form of the RFC3
      gene product (Rfc3p) has been overproduced in E. coli and purified to
      homogeneity. Purified Rfc3p has an ATPase activity that is markedly stimulated by
      single-stranded DNA but not by double-stranded DNA or RNA.

PMID- 8302860
TI  - Calcicludine, a venom peptide of the Kunitz-type protease inhibitor family, is a
      potent blocker of high-threshold Ca2+ channels with a high affinity for L-type
      channels in cerebellar granule neurons.
AB  - Calcicludine (CaC) is a 60-amino acid polypeptide from the venom of Dendroaspis
      angusticeps. It is structurally homologous to the Kunitz-type protease inhibitor,
      to dendrotoxins, which block K+ channels, and to the protease inhibitor domain of
      the amyloid beta protein that accumulates in Alzheimer disease. Voltage-clamp
      experiments on a variety of excitable cells have shown that CaC specifically
      blocks most of the high-threshold Ca2+ channels (L-, N-, or P-type) in the 10-100
      nM range. Particularly high densities of specific 125I-labeled CaC binding sites
      were found in the olfactory bulb, in the molecular layer of the dentate gyrus and
      the stratum oriens of CA3 field in the hippocampal formation, and in the granular
      layer of the cerebellum. 125I-labeled CaC binds with a high affinity (Kd = 15 pM)
      to a single class of noninteracting sites in rat olfactory bulb microsomes. The
      distribution of CaC binding sites in cerebella of three mutant mice (Weaver,
      Reeler, and Purkinje cell degeneration) clearly shows that the specific high
      affinity labeling is associated with granule cells. Electrophysiological
      experiments on rat cerebellar granule neurons in primary culture have shown that
      CaC potently blocks the L-type component of the Ca2+ current (K0.5 = 0.2 nM).
      Then CaC, in the nanomolar range, appears to be a highly potent blocker of an L
      subtype of neuronal Ca2+ channels.

PMID- 8302861
TI  - Molecular model of the specificity pocket of the hepatitis C virus protease:
      implications for substrate recognition.
AB  - We have built a model of the specificity pocket of the protease of hepatitis C
      virus on the basis of the known structures of trypsin-like serine proteases and
      of the conservation pattern of the protease sequences among various hepatitis C
      strains. The model allowed us to predict that the substrate of this protease
      should have a cysteine residue in position P1. This hypothesis was subsequently
      proved by N-terminal sequencing of two products of the protease. The success of
      this "blind" test increases our confidence in the overall correctness of our
      proposed alignment of the enzyme sequence with those of other proteases of known
      structure and constitutes a first step in the construction of a complete model of
      the viral protease domain.

PMID- 8302863
TI  - Identification of a vitamin D-response element in the rat calcidiol (25
      hydroxyvitamin D3) 24-hydroxylase gene.
AB  - The calcidiol (25-hydroxyvitamin D3) 24-hydroxylase is one of the key enzymes in
      the metabolism of vitamin D. This enzyme acts on both calcidiol and calcitriol
      (1,25-dihydroxyvitamin D3) to initiate degradation of these potent vitamin D
      metabolites and is tightly regulated. Calcitriol itself induces this enzyme and
      acts at the transcriptional level. Transcriptional regulation of genes by
      calcitriol has been shown to occur via the vitamin D-receptor binding to a
      vitamin D-response element located upstream of the transcription start site. We
      now report a vitamin D-response element located between nt -262 and nt -238 of
      the rat calcidiol 24-hydroxylase gene. This sequence binds the calcitriol
      receptor and confers vitamin D-dependent transactivation of transcription to its
      own, as well as heterologous, promoter.

PMID- 8302862
TI  - A simpler sort of antibody.
AB  - The monoclonal antibody NEMO is directed against a molecule expressed by human
      cells of the melanocytic lineage. Although obtained by conventional immunization
      and fusion procedures, NEMO consists solely of kappa light chain. SDS/PAGE
      analysis indicates that the kappa chains are present as both monomers and dimers.
      When these two forms were separated by gel filtration, only the monomeric form
      bound antigen. As kappa light chains from the myeloma MOPC-41 and the hybridoma
      MORK do not bind to the melanocytic cells, we conclude that the binding
      specificity of NEMO resides in the variable region.

PMID- 8302864
TI  - Splicing function of mammalian U6 small nuclear RNA: conserved positions in
      central domain and helix I are essential during the first and second step of pre
      mRNA splicing.
AB  - On the basis of mutational analyses in yeast, the highly conserved ACAGAGA
      sequence of U6 small nuclear RNA (snRNA) and the adjacent U6-U2 helix I have been
      proposed to be part of the active center of the spliceosome. We report here a
      detailed analysis of the human U6 snRNA sequence requirements during the first
      and second step of splicing, using a mammalian in vitro splicing-complementation
      system and a mutational approach. Positions A53G54C55 (helix Ib) were identified
      as important specifically for the first step, but not for spliceosome assembly.
      A45 of the ACAGAGA sequence and U52 of helix Ia function during the second step;
      in addition, the bulge separating helices Ia and Ib appears critical for the
      second step. In contrast, no splicing-essential sequences could be identified in
      the central domain upstream of the ACAGAGA sequence. In sum, our data demonstrate
      for the mammalian splicing system that discrete positions within the ACAGAGA
      sequence and helix I of U6 snRNA function during the first and second step of
      splicing, suggesting that these two sequence elements are closely associated with
      the catalytic center of the spliceosome. Comparison with previous results in
      yeast indicates a fundamental conservation of the U6 snRNA function in the pre
      mRNA splicing mechanism.

PMID- 8302865
TI  - Evidence for a non-alpha-helical DNA-binding motif in the Rel homology region.
AB  - The Rel family of transcription factors serve as terminal messengers in a variety
      of developmental and receptor-mediated signaling pathways. These proteins are
      related by a domain of approximately 280 amino acids, the Rel homology region,
      which mediates dimerization and sequence-specific binding to DNA. Here we report
      the use of photocrosslinking and site-directed mutagenesis to identify specific
      contact partners in a Rel protein-DNA interface. Within the Rel homology region
      of NF-kappa B p50 (also known as KBF1), two amino acid residues were identified
      by photocrosslinking to adjacent bases in a beta-interferon regulatory element.
      Secondary structure analysis suggests that the DNA-binding motif of the Rel
      homology region comprises a beta-turn-beta structure, in contrast to the alpha
      helical motifs so commonly observed in transcription factors.

PMID- 8302866
TI  - Role of N-linked oligosaccharide recognition, glucose trimming, and calnexin in
      glycoprotein folding and quality control.
AB  - Using a pulse-chase approach combined with immunoprecipitation, we showed that
      newly synthesized influenza virus hemagglutinin (HA) and vesicular stomatitis
      virus G protein associate transiently during their folding with calnexin, a
      membrane-bound endoplasmic reticulum (ER) chaperone. Inhibitors of N-linked
      glycosylation (tunicamycin) and glucosidases I and II (castanospermine and 1
      deoxynojirimycin) prevented the association, whereas inhibitors of ER alpha
      mannosidases did not. Our results indicated that binding of these viral
      glycoproteins to calnexin correlated closely with the composition of their N
      linked oligosaccharide side chains. Proteins with monoglucosylated
      oligosaccharides were the most likely binding species. On the basis of our data
      and existing information concerning the role of monoglucosylated oligosaccharides
      on glycoproteins, we propose that the ER contains a unique folding and quality
      control machinery in which calnexin acts as a chaperone that binds proteins with
      partially glucose-trimmed carbohydrate side chains. In this model glucosidases I
      and II serve as signal modifiers and UDP-glucose:glycoprotein
      glucosyltransferase, as a folding sensor.

PMID- 8302867
TI  - Phylogenetic analysis of RNA editing: a primitive genetic phenomenon.
AB  - RNA editing by extensive uridine addition and deletion creates over 90% of the
      amino acid codons in the cytochrome-c oxidase subunit III (COIII) transcript in
      Trypanosoma brucei and Herpetomonas, whereas editing of the COIII transcripts in
      Leishmania tarentolae and Crithidia fasciculata generates only 6% of the amino
      acid codons and is limited to the 5' ends. Is extensive RNA editing a primitive
      or derived character? We constructed a phylogenetic tree based on nuclear small
      subunit and mitochondrial large- and small-subunit ribosomal RNA sequences for
      nine species of kinetoplastid protozoa. Our results suggest that extensive
      editing is a primitive genetic phenomenon that has disappeared in recent
      evolutionary time and also that there have been multiple losses of the digenetic
      lifestyle by loss of the vertebrate host in parasite evolution.

PMID- 8302868
TI  - Candida albicans estrogen-binding protein gene encodes an oxidoreductase that is
      inhibited by estradiol.
AB  - Candida albicans, the most common fungal pathogen of humans, possesses an
      estrogen-binding protein (EBP) that binds mammalian estrogens with high affinity.
      We report here the cloning and complete nucleotide sequence of a gene encoding a
      C. albicans EBP. Amino acid sequences obtained from cyanogen bromide fragments of
      purified EBP were used to design oligonucleotide primers for PCR. An 800-bp
      product was amplified and used to screen a C. albicans genomic library. A clone
      was isolated containing an insert with an open reading frame of 1221 nt capable
      of encoding a protein with 407 amino acids and having a calculated molecular mass
      of 46,073 Da, the estimated size of EBP. The cloned gene, expressed in
      Escherichia coli as a lacZ fusion protein, demonstrated high-affinity binding for
      estradiol and a competition profile comparable to C. albicans wild-type EBP.
      Northern blots of C. albicans RNA revealed a single transcript of approximately
      1600 nt, whereas Southern blots identified three hybridizing fragments. Computer
      searches of data bases showed that EBP shares a 46% amino acid identity with the
      old yellow enzyme, an oxidoreductase from Saccharomyces cerevisiae, but was
      unrelated to the human estrogen receptor as previously speculated. In addition, a
      51-amino acid region of EBP is highly conserved among a group of flavoproteins
      including old yellow enzyme. Expressed EBP was shown to exhibit oxidoreductase
      activity that could be inhibited by 17 beta-estradiol in vitro. In conclusion,
      the EBP from C. albicans has no evident homology to the mammalian steroid
      receptor superfamily but appears to be a member of a recently identified family
      of flavoproteins.

PMID- 8302869
TI  - Arabidopsis thaliana contains two differentially expressed 3-hydroxy-3
      methylglutaryl-CoA reductase genes, which encode microsomal forms of the enzyme.
AB  - The enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR; EC 1.1.1.34) catalyzes
      the first rate-limiting step in plant isoprenoid biosynthesis. Arabidopsis
      thaliana contains two genes, HMG1 and HMG2, that encode HMGR. We have cloned
      these two genes and analyzed their structure and expression. HMG1 and HMG2
      consist of four exons and three small introns that interrupt the coding sequence
      at equivalent positions. The two genes share sequence similarity in the coding
      regions but not in the 5'- or 3'-flanking regions. HMG1 mRNA is detected in all
      tissues, whereas the presence of HMG2 mRNA is restricted to young seedlings,
      roots, and inflorescences. The similarity between the two encoded proteins (HMGR1
      and HMGR2) is restricted to the regions corresponding to the membrane and the
      catalytic domains. Arabidopsis HMGR2 represents a divergent form of the enzyme
      that has no counterpart among plant HMGRs characterized so far. By using a
      coupled in vitro transcription-translation assay, we show that both HMGR1 and
      HMGR2 are cotranslationally inserted into endoplasmic reticulum-derived
      microsomal membranes. Our results suggest that the endoplasmic reticulum is the
      only cell compartment for the targeting of HMGR in Arabidopsis and support the
      hypothesis that in higher plants the formation of mevalonate occurs solely in the
      cytosol.

PMID- 8302870
TI  - Several mRNAs with variable 3' untranslated regions and different stability
      encode the human PR264/SC35 splicing factor.
AB  - We have recently established that several mRNAs encode the PR264/SC35 splicing
      factor and that their expression is related to that of c-Myb in human
      hematopoietic cells. We now report that the various PR264 mRNAs whose expression
      is transactivated by c-Myb proteins encode an identical PR264/SC35 polypeptide.
      These mRNAs differ only in their 3' untranslated sequences and exhibit
      significantly different half-lives. We also show that there is a direct
      correlation between the length of the 3' untranslated region and the stability of
      the mRNA species. Given that 5' and 3' splice site selection mediated by the
      PR264/SC35 splicing factor is concentration-dependent, we postulate that
      alternative splicing of the 3' untranslated sequences might represent another key
      element in regulating the levels of PR264/SC35 expression during hematopoietic
      differentiation.

PMID- 8302871
TI  - Determination of spin-label orientation within the myosin head.
AB  - Current methods of analyzing EPR spectra of spin-labeled muscle fibers allow the
      determination of spin-label orientation within the fiber, rather than the
      orientation of the myosin head itself. In order to describe the orientational
      distribution of spin labeled myosin heads within the muscle fibers, the
      orientation of the spin label within the myosin head must be known. The
      iodoacetamide label orientation in the myosin head was determined to be (16.8
      degrees, 28.3 degrees, 4.2 degrees) or (16.6 degrees, 72.0 degrees, 4.3 degrees).
      These Eulerian angles were obtained from the analysis of EPR spectra of fibers
      decorated with labeled myosin heads in the absence of ATP, with the assumption
      that the head's tilt angle is 40 degrees, as observed in a recent EM study
      [Pollard, T., Bhandari, D., Maupin, P., Wachsstock, D., Weeds, A. & Zot, H.
      (1993) Biophys. J. 64, 454-471]. Knowledge of spin-label orientation will allow
      for quantitative determination of myosin head orientation in the various states
      of the contractile cycle.

PMID- 8302872
TI  - A proposed superfamily of transposase genes: transposon-like elements in ciliated
      protozoa and a common "D35E" motif.
AB  - The transposon-like elements TBE1, Tec1, and Tec2 of hypotrichous ciliated
      protozoa appear to encode a protein that belongs to the IS630-Tc1 family of
      transposases. The Anabaena IS895 transposase also is placed in this family. We
      note that most family members transpose into the dinucleotide target, TA, and
      that members with eukaryotic hosts have a tendency for somatic excision that is
      carried to an extreme by the ciliate elements. Alignments including the
      additional members, and also mariner elements, show that transposases of this
      family share strongly conserved residues in a large C-terminal portion, including
      a fully conserved dipeptide, Asp-Glu (DE), and a block consisting of a fully
      conserved Asp and highly conserved Glu, separated by 34 or 35 residues (D35E).
      This D35E motif likely is homologous to the previously characterized D35E motif
      of the family of retroviral-retrotransposon integrases and IS3-like transposases.
      Because it is known that the IS3-retroposon D35E region is a critical portion of
      a domain capable of various in vitro transposition-related reactions, the results
      suggest that the two families share homologous catalytic transposase domains and
      that members of both families may share a common transposition mechanism.

PMID- 8302873
TI  - Cytoplasmic sequences of the growth hormone receptor necessary for signal
      transduction.
AB  - To study structure-function relationships of the growth hormone (GH) receptor
      (GHR), two functional systems have been developed. CHO cells were transiently
      cotransfected with the cDNA encoding the full-length rat GHR and with a construct
      consisting of the 5' flanking region of one of two GH-dependent genes encoding
      ovine beta-lactoglobulin or serine protease inhibitor 2.1 (Spi 2.1, formerly
      Spi.1; the corresponding rat gene has recently been redesignated Spin2a) coupled
      to the bacterial reporter gene encoding chloramphenicol acetyltransferase (CAT).
      Transfected cells were grown in the absence and presence of human GH and
      dexamethasone for the Spi 2.1 gene construct. GH was able to activate each
      promoter (with approximately 4-fold induction of CAT activity) in a dose
      dependent manner. For both tests, the maximal effect was observed at 20 nM human
      GH. These tests have been used to identify functional domains of the GHR. Two
      truncated (T) GHRs, lacking most or part of the cytoplasmic domain [called T276
      (ending at residue 276) and T436 (ending at residue 436)], were unable to
      stimulate CAT activity. The GHR contains a proline-rich region, called "Box I,"
      conserved in the cytokine/GH/prolactin receptor family. Alanine substitutions for
      the four prolines of GHR Box I were introduced. Single proline-to-alanine
      mutations did not affect the functional activity of the GHR. However,
      modification of the four prolines together or deletion of the Box I (15 amino
      acids between positions 279 and 293) resulted in the complete absence of GH
      stimulation. Thus, the proline-rich region, shown to be important for other
      members of this receptor superfamily, is also critical for GH signal
      transduction.

PMID- 8302874
TI  - Supramolecular organization of the mammalian translation system.
AB  - Although evidence suggests that the protein synthetic machinery is organized
      within cells, this point has been difficult to prove because any organization
      that might exist is lost upon preparation of the cell-free systems usually used
      to study translation in vitro. To examine this process under conditions more
      representative of the intact cell, we have developed an active protein
      synthesizing system using Chinese hamster ovary (CHO) cells permeabilized with
      the plant glycoside saponin. This procedure renders cells permeable to trypan
      blue and exogenous tRNA, but there is little release of endogenous
      macromolecules. Protein synthesis in this system proceeds at the same rate as
      that in intact cells and is about 40-fold faster than that in a cell-free system
      prepared from the same cells. Active protein synthesis in this system requires
      the addition of only Mg2+, K+, and creatine phosphate, with a small further
      stimulation by ATP and an amino acid mixture; no exogenous macromolecules are
      necessary. The proteins synthesized in this system are indistinguishable from
      those made by the intact cell, and the channeling of aminoacyl-tRNA observed in
      vivo is maintained. Our data suggest that the permeabilized cell system retains
      the protein-synthesizing capabilities of the intact cell and presumably its
      internal structure as well. Studies with this system demonstrate that the protein
      synthesizing apparatus is highly organized and that its macromolecular components
      are not freely diffusible in mammalian cells.

PMID- 8302875
TI  - Humanization of murine monoclonal antibodies through variable domain resurfacing.
AB  - Two murine monoclonal antibodies, N901 (anti-CD56) and anti-B4 (anti-CD19), were
      humanized by a process we call "resurfacing." A systematic analysis of known
      antibody structures has been used to determine the relative solvent accessibility
      distributions of amino acid residues in murine and human antibody variable (Fv)
      regions and has shown that the sequence alignment positions of surface amino
      acids for human and murine variable region heavy (VH) and light (VL) chains are
      conserved with 98% fidelity across species. While the amino acid usage at these
      surface positions creates surface residue patterns that are conserved within
      species, there are no identical patterns across species. However, surprisingly
      few amino acid changes need to be made to convert a murine Fv surface pattern to
      that characteristic of a human surface. Resurfacing was used to change the
      patterns of surface accessible residues in the Fv regions of the N901 and anti-B4
      antibodies to resemble those found on the Fv regions of human antibody sequences.
      Two different procedures for selecting a human sequence were compared. For anti
      B4, a data base of clonally derived human VL-VH sequence pairs was used, while
      for N901, sequences for VL and VH were independently selected from the Kabat et
      al. data base [Kabat, E. A., Wu, T. T., Reid-Miller, M., Perry, H. M. &
      Gottesman, K. S. (1991) Sequences of Proteins of Immunological Interest (DHHS,
      Washington, DC), 5th Ed.]. Resurfaced N901 and anti-B4 antibodies had apparent
      affinities for their cell surface ligands that were identical to those of their
      respective parent murine antibodies. These data provide evidence that, despite
      the differences in the surfaces of mouse and human Fv regions, it is possible to
      substitute one for the other while retaining full antigen binding affinity.

PMID- 8302876
TI  - Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a group of inherited human diseases in which
      photoreceptor degeneration leads to visual loss and eventually to blindness.
      Although mutations in the rhodopsin, peripherin, and cGMP phosphodiesterase genes
      have been identified in some forms of RP, it remains to be determined whether
      these mutations lead to photoreceptor cell death through necrotic or apoptotic
      mechanisms. In this paper, we report a test of the hypothesis that photoreceptor
      cell death occurs by an apoptotic mechanism in three mouse models of RP: retinal
      degeneration slow (rds) caused by a peripherin mutation, retinal degeneration
      (rd) caused by a defect in cGMP phosphodiesterase, and transgenic mice carrying a
      rhodopsin Q344ter mutation responsible for autosomal dominant RP. Two
      complementary techniques were used to detect apoptosis-specific internucleosomal
      DNA fragmentation: agarose gel electrophoresis and in situ labeling of apoptotic
      cells by terminal dUTP nick end labeling. Both methods showed extensive apoptosis
      of photoreceptors in all three mouse models of retinal degeneration. We also show
      that apoptotic death occurs in the retina during normal development, suggesting
      that different mechanisms can cause photoreceptor death by activating an
      intrinsic death program in these cells. These findings raise the possibility that
      retinal degenerations may be slowed by interfering with the apoptotic mechanism
      itself.

PMID- 8302877
TI  - Multiple forms of poly(A) polymerases in human cells.
AB  - We have cloned human poly(A) polymerase (PAP) mRNA as cDNA in Escherichia coli.
      The primary structure of the mRNA was determined and compared to the bovine PAP
      mRNA sequence. The two sequences were 97% identical at the nucleotide level,
      which translated into 99% similarity at the amino acid level. Polypeptides
      representing recombinant PAP were expressed in E. coli, purified, and used as
      antigens to generate monoclonal antibodies. Western blot analysis using these
      monoclonal antibodies as probes revealed three PAPs, having estimated molecular
      masses of 90, 100, and 106 kDa in HeLa cell extracts. Fractionation of HeLa cells
      showed that the 90-kDa polypeptide was nuclear while the 100- and 106-kDa species
      were present in both nuclear and cytoplasmic fractions. The 106-kDa PAP was most
      likely a phosphorylated derivative of the 100-kDa species. PAP activity was
      recovered in vitro by using purified recombinant human PAP. Subsequent mutational
      analysis revealed that both the N- and C-terminal regions of PAP were important
      for activity and suggested that cleavage and polyadenylylation specificity factor
      (CPSF) interacted with the C-terminal region of PAP. Interestingly, tentative
      phosphorylation sites have been identified in this region, suggesting that
      phosphorylation/dephosphorylation may regulate the interaction between the two
      polyadenylylation factors PAP and CPSF.

PMID- 8302880
TI  - R. A. McCance (9 December 1898-5 March 1993).

PMID- 8302879
TI  - Concerted evolution at the population level: pupfish HindIII satellite DNA
      sequences.
AB  - The canonical monomers (approximately 170 bp) of an abundant (1.9 x 10(6) copies
      per diploid genome) satellite DNA sequence family in the genome of Cyprinodon
      variegatus, a "pupfish" that ranges along the Atlantic coast from Cape Cod to
      central Mexico, are divergent in base sequence in 10 of 12 samples collected from
      natural populations. The divergence involves substitutions, deletions, and
      insertions, is marked in scope (mean pairwise sequence similarity = 61.6%; range
      = 35-95.9%), is largely confined to the 3' half of the monomer, and is not
      correlated with the distance among collecting sites. Repetitive cloning and
      direct genomic sequencing experiments failed to detect intrapopulation and
      intraindividual variation, suggesting high levels of sequence homogeneity within
      populations. The satellite sequence has therefore undergone "concerted
      evolution," at the level of the local population. Concerted evolution has
      previously almost always been discussed in terms of the divergence of species or
      higher taxa; its intraspecific occurrence apparently has not been reported
      previously. The generality of the observation is difficult to evaluate, for
      although satellite DNAs from a large number of organisms have been studied in
      detail, there appear to be little or no other data on their sequence variation in
      natural populations. The relationship (if any) between concerted, population
      level, satellite DNA divergence and the extent of gene flow/genetic isolation
      among conspecific natural populations remains to be established.

PMID- 8302881
TI  - The Sir David Cuthbertson Medal Lecture 1992. The immunological and metabolic
      effects of L-arginine in human cancer.

PMID- 8302878
TI  - High-affinity binding sites for related fibroblast growth factor ligands reside
      within different receptor immunoglobulin-like domains.
AB  - Growth factors of the fibroblast growth factor (FGF) family bind receptors whose
      external domains are organized in a series of immunoglobulin-like loops. We
      engineered expression constructs in which cDNAs encoding individual
      immunoglobulin-like domains of the keratinocyte growth factor (KGF/FGF-7)
      receptor were fused to the mouse immunoglobulin heavy chain Fc domain (HFc). Each
      chimera was efficiently secreted from NIH 3T3 transfectants and migrated at the
      predicted molecular mass after SDS/PAGE. Scatchard analysis revealed that the
      chimera containing immunoglobulin-like domains 2 (D2) and 3 (D3) bound KGF and
      acidic FGF at high affinities comparable to the native receptor. However,
      individual immunoglobulin-like domain chimeras demonstrated marked specificity in
      their ligand interactions. D2-HFc bound acidic FGF at high affinity, whereas it
      did not detectably interact with KGF. Conversely, D3-HFc bound KGF at high
      affinity but exhibited no detectable interaction with acidic FGF. Their selective
      ligand binding properties were confirmed by the specific neutralization of acidic
      FGF or KGF mitogenic activity using D2 or D3 HFc, respectively. All of these
      findings establish that the major binding sites for related FGF ligands are
      localized to distinct receptor immunoglobulin-like domains.

PMID- 8302882
TI  - Some aspects of the biology of feeding and growth in fish.

PMID- 8302883
TI  - Nutritional requirements of fish.

PMID- 8302884
TI  - Variation in individual food consumption rates of fish and its implications for
      the study of fish nutrition and physiology.

PMID- 8302885
TI  - Epidemiological aspects of fish in the diet.

PMID- 8302886
TI  - Variability of the composition of fish oils: significance for the diet.

PMID- 8302887
TI  - Marine oils: metabolic effects and role in human nutrition.

PMID- 8302888
TI  - Lessons from extra digits.

PMID- 8302889
TI  - In vivo experimental induction of interdigital tissue chondrogenesis in the avian
      limb bud results in the formation of extradigits. Effects of local microinjection
      of staurosporine, zinc chloride and growth factors.
AB  - In previous studies we had found that at late stages of development, when the
      early patterning control mechanism have ceased to act, the chick limb bud is able
      to form fully differentiated extradigits by subjecting the interdigital spaces to
      ectoderm removal. In this study we attempted to mimic this phenomenon by using
      local microinjections of substances which presumably have a biological action on
      the interdigital mesenchyme. Microinjection of staurosporine results in the
      formation of fully differentiated extradigits. The action of this drug appears to
      be due to the induction of chondrogenesis after the inhibition of the protein
      kinase C. Zinc chloride administration also causes ectopic chondrogenesis but it
      seems to act by arresting the interdigital cell death program through
      endonuclease inhibition. A clear differentiation of the zinc-induced cartilages
      into extradigits was no detected. This can be explained by the accompanying
      damage caused by zinc in the growing limb mesenchyme as deduced by the high
      incidence of hypophalangy in the normal digits. Both TGF beta 1 and TGF beta 2
      have a weak effect as inducers of interdigital chondrogenesis; presumably they
      act by inducing chondrogenetic differentiation. Neither FGF nor EGF has any
      effect when administered by local microinjection. These results show that ectopic
      interdigital chondrogenesis induced by drug administration results in the
      differentiation of extradigits. This suggests that once a cartilage is formed in
      the autopodium it triggers a new signalling stage which leads to the
      morphogenesis of a digit. This morphogenetic process involves the patterning of
      skeleton, joints and tendons. In accordance with these observations, it can be
      proposed that early patterning of the limb results in the establishment of an
      autopodium with a defined but still plastic skeletal distribution pattern, while
      morphogenesis of each autopodial element would take place at a second stage by
      the activation of new signalling processes.

PMID- 8302890
TI  - Effects of ectoderm co-culture and conditioned medium on the limb mesoderm in
      vitro.
AB  - Undissociated mesoderm placed onto collagen gels forms three subpopulations of
      mesenchyme which differentiate along myogenic, chondrogenic and fibrogenic
      phenotypes. Co-culture with ectoderm appears to inhibit the formation of distinct
      cartilage elements and myotubes by interfering with the differentiation of
      chondrogenic and fibrogenic progenitors. Addition of CCM enriched in ES antigens
      enhances the effects of the ectoderm on chondrogenesis. Culture in the presence
      of CCM alone retards chondrogenesis and almost completely inhibits myogenesis.
      These results suggest that the primary effect of ectoderm or CCM in our culture
      system is on myogenic and chondrogenic differentiation, and ES antigens, if
      responsible for these effects, appear to have no role in pattern formation.

PMID- 8302891
TI  - Gli3 expression is affected in the morphogenetic mouse mutants add and Xt.
AB  - We investigated the relation between the recessive mutation add caused by
      insertional mutagenesis of a transgene and the dominant mutation extra-toes (Xt)
      which display similar effects on limb morphogenesis. The transgene insertion in
      add mapped close to the 5' end of the zinc finger gene Gli3 and 5'sequences of
      Gli3 were deleted in Xt. Expression analysis revealed a reduction of the Gli3 RNA
      level in both add and Xt mice. Thus, it is very likely that add and Xt are
      alleles of the Gli3 gene.

PMID- 8302892
TI  - The pattern of skeletal malformations in Dh/+ and Dh/Dh day 18 fetuses.

PMID- 8302893
TI  - Analysis of the mutant axolotl short toes.

PMID- 8302894
TI  - Development and regeneration of limbs in the short toes axolotl mutant.

PMID- 8302895
TI  - Transfection of adult newt limb blastema cells in vivo: increased efficiency with
      direct injection of plasmid DNA.

PMID- 8302896
TI  - Affinophoresis as a test of axolotl accessory limbs.

PMID- 8302897
TI  - Effect of cyclophosphamide on limb regeneration in stages of Bufo regularis
      reuss.
AB  - Pre-amputation treatment in both stages (53 and 56) caused a profound decline in
      limb regeneration abilities and gave heteromorphic regenerates with smaller
      number of toes in the early stage, while in the later one, it suppressed
      completely the regeneration of toes or toe protuberances; otherwise partial or
      complete restoration of the shank. CY treatment concomitant with amputation
      caused intensive enhancement of regeneration in the early stage, while in the
      later one it activated regeneration to a lesser degree.

PMID- 8302898
TI  - Phosphoprotein phosphatase activity in regenerating forelimbs of adult newts,
      Notophthalmus viridescens.
AB  - Traditional signal transduction pathways appear to be operating during amphibian
      forelimb regeneration, as in other developing systems. A consistent picture
      appears to be developing that suggests that growth factors promoting
      proliferation during regeneration act through cAMP-independent mechanisms while
      factors that modulate differentiation and morphogenesis include signaling
      pathways in which cAMP participates. Although our understanding of these pathways
      is far from complete, it is becoming increasingly evident that further
      characterization of signal transduction events will facilitate (a) identifying
      major signaling substances, (b) determining the cellular events in regeneration
      that they modulate, and (c) defining the mechanisms through which they act. The
      present study demonstrates that PPtases, and in particular PTPases, can be
      studied in regenerating newt limbs. More importantly, this investigation
      demonstrates that there are progressive and significant increases in PPtase
      activity during regeneration. Moreover, the observed patterns of PPtase activity
      during regeneration conform to an emerging picture that ligands acting through
      receptors possessing intrinsic tyrosine kinase activity promote proliferation
      within the regeneration blastema. However, the substrates used in this study
      precluded acquiring insights about modulating effects of serine/threonine kinases
      (e.g., PKA and PKC). Nevertheless, these data suggest that activation of PPtases
      contribute to the orchestration of the diverse cellular activities required to
      regenerate a vertebrate appendage.

PMID- 8302899
TI  - Phalangeal regrowth in rodents: postamputational bone regrowth depends upon the
      level of amputation.
AB  - Conflicting reports of distal phalangeal regrowth prompted a reexamination of
      bone growth following phalangeal amputation in mammals. Digits of neonatal and
      adult mice and rats were amputated at various levels. The short-term response was
      examined on histological sections, and long-term growth was documented by
      alizarin red-staining of KOH-digested digits. Three patterns of response were
      seen to correspond to three general levels of amputation. Complete bone
      regeneration occurred frequently by five weeks following amputation through the
      distal one-quarter of the distal phalanx. Amputation through the central region
      of the distal phalanx yielded substantial bone growth, but the form of the
      regrowth was imperfect even three months after amputation. Amputation through
      more proximal levels of the digit yielded no significant elongation. To
      investigate why the response varies in relation to the level of amputation, we
      are conducting both in vivo and in vitro experiments. We have learned that simple
      avulsion of the nail plate provokes substantial remodeling of the distal phalanx.
      We are further exploring the trophic influence of nail organ on bone structure
      and growth in vivo. We have also recently determined that entire digits may be
      kept alive in vitro when cultured in DMEM:F-12:BGJb medium supplemented with
      insulin, EGF and FGF. This system sufficiently replicates in vivo conditions such
      that osteogenesis occurs both endosteally and distal to the amputation plane in
      vitro. The effects of growth factors, retinoic acid, and the presence or absence
      of nail organ components on amputational bone growth at all three levels are
      currently being studied in vitro. The goal of these studies is to determine why
      bone fails to grow, undergoes hyperplasia, or regenerates following amputation at
      different levels in mammals.

PMID- 8302900
TI  - The regenerative capacity of the limb region in rat embryos following the removal
      of the fore-limb bud.

PMID- 8302901
TI  - Monoclonal antibody WE6 identifies an antigen that is up-regulated in the wound
      epithelium of newts and frogs.

PMID- 8302902
TI  - Scanning electron microscopy of the early innervation of the wound epithelium of
      the amputated forelimb in the adult newt Notophthalmus viridescens.

PMID- 8302903
TI  - MPLB-2: a posterior signaling cell line derived from the mouse limb bud.

PMID- 8302904
TI  - Development of immortalized cells derived from 13DPC mouse limb buds as a system
      to study the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2)
      on limb bud cell differentiation.

PMID- 8302905
TI  - Axial and paraxial influences on the origin of the chick embryo limb.

PMID- 8302906
TI  - Endothelial cell differentiation in the chick limb.

PMID- 8302907
TI  - Cells of the apical ectodermal ridge in quail limb buds are coupled to one
      another but are isolated from subjacent mesoderm.

PMID- 8302908
TI  - Morphogenetic potential of leg bud mesoderm to express limb-like characteristics
      in vitro.

PMID- 8302909
TI  - In vitro maintenance of posterior (ZPA) signaling in mouse limb bud cells.

PMID- 8302910
TI  - Estimation of intracellular pH by computer assisted imaging in the developing
      mouse forelimb bud exposed to acetazolamide.

PMID- 8302911
TI  - Chorionic villus sampling and limb defects.

PMID- 8302912
TI  - Most human lower limb malformations appear to result from postspecification
      insults.

PMID- 8302914
TI  - Monthly prostaglandin bibliography prepared by University of Sheffield Biomedical
      Information Service.

PMID- 8302913
TI  - Making the connection: exploring classical concepts in normal and abnormal limb
      development using contemporary approaches.
AB  - Classical studies of the vertebrate limb have provided a firm foundation for
      recent investigations into the molecular control of mechanisms governing limb
      patterning. The early studies revealed the importance of inductive tissue
      interactions in developing systems, the spatiotemporal restrictions of these
      interactions, and the conservation of inductive signals between different tissues
      and even different species. They incorporated a number of different experimental
      approaches, including: homologous and heterologous tissue grafting and
      recombination, the investigation of several limb mutations, and examination of
      the response of normal limb tissue to a variety of teratogenic treatments. While
      some of the mutations studied only affected the limbs, most were highly
      pleiotropic, producing complex syndromes that altered the development of several
      embryonic structures in addition to the limbs. Some of these syndromes could be
      partially or completely phenocopied (mimicked) by specific chemical or physical
      treatments. One such gene-phenocopy pairing that we have studied is that of the
      mutation wingless-2 and the syndrome produced by treatment with retinoic acid.
      Another aspect of abnormal pattern formation we explored is the interaction
      between wingless-2 and eudiplopodia.

PMID- 8302915
TI  - Eicosanoids and ovulation.
AB  - PGs and probably other eicosanoids play a fundamental role in the process of
      ovulation, more specifically in the mechanism of follicle wall rupture. Although
      the nature of this role has yet to be established a number of plausible theories
      exist. It seems likely that altered PG metabolism is responsible for some cases
      of human female subfertility. The potential for fertility control by PG
      inhibition is an exciting possibility for the future.

PMID- 8302916
TI  - Short chain fatty acid-induced hyperventilation is due to PGF2-alpha.
AB  - While studying the significance of the short chain fatty acids (SCFAs) in the
      pathogenesis of hyperventilation, we have found that experimental rabbits
      injected with SCFA sodium salt (4 mmol/kg b.wt) develop hyperventilation 20 min
      later. This hyperventilation results in a decrease of PCO2 in the arterial blood
      from 32.05 +/- 1.18 to 24.55 +/- 0.83 (p < 0.001). The SCFAs also bring about
      pronounced mixed alkalosis. The prostaglandin F2-alpha (PGF2-alpha) in both the
      arterial and venous blood of rabbits increased significantly after treatment with
      SCFAs salts. If the rabbits are pretreated with indomethacin (10 mg/kg), the
      SCFAs do not cause hyperventilation. Therefore we can conclude, that the SCFAs
      bring about hyperventilation through an increase in the PGF2-alpha synthesis.

PMID- 8302917
TI  - Arachidonic acid inhibits electrically induced intracellular calcium transients
      in neonatal rat cardiomyocytes.

PMID- 8302918
TI  - Prostaglandin E2 antagonizes gingival fibroblast proliferation stimulated by
      interleukin-1 beta.
AB  - Treatment of human gingival fibroblasts with prostaglandin E2 (PGE2) resulted in
      significant concentration-dependent inhibition in deoxyribonucleic acid (DNA)
      synthesis (8.40-37.89%), while indomethacin (INDO) (PG inhibitor), interleukin-1
      beta (IL-1 beta) or IL-1 beta+INDO caused a significant and dose-dependent
      increase in DNA synthesis. Addition of PGE2 to culture media containing IL-1 beta
      and INDO caused a significant concentration-dependent reduction in IL-1 beta- and
      INDO-induced stimulation of DNA synthesis. The findings suggest that IL-1 beta
      and PGE2, which are also produced by fibroblasts, could play an important role in
      regulation of gingival tissue development and wound healing, and their modulation
      may have therapeutic potential.

PMID- 8302919
TI  - Measurements of leukotrienes in human plasma by solid phase extraction and high
      performance liquid chromatography.
AB  - Leukotrienes (LTs) are biologically active compounds derived from lipoxygenase
      catalyzed metabolism of arachidonic acid in mammalian tissues. The present report
      describes a simple method for extraction and isolation of dihydroxy-LTs; LTB4,
      LTB5 and the peptido-LTs; LTC4, LTD4 and LTE4 from human plasma, using a
      pretreatment cartridge which utilizes both hydrophobic and ion-exchange
      interactions. 5 ml acidified plasma or acetate buffer containing commercially
      available LT standards were passed through the cartridges under suction, and the
      absorbed LTs were subsequently eluted in a stepwise manner with acetate buffer
      containing increasing amounts of methanol. The eluted LTs were analyzed by
      reversed-phase high performance liquid chromatography (HPLC) on octadecylsilyl
      (ODS)-silica, using a Waters HPLC unit. Both with plasma and acetate buffer the
      present methodology resulted in good separation of the LTs with a total run-time
      of less than 32 min. Recovery of dihydroxy-LTs was approximately 80% (range 73
      82%) both when the standards were dissolved in plasma and in acetate buffer.
      Recovery of the peptido-LTs was, however somewhat lower (47-50%). It should be
      noted that the present method has the advantage that exposure to chemicals of
      high toxicity is avoided.

PMID- 8302920
TI  - Aqueous extracts of garlic (Allium sativum) inhibit prostaglandin synthesis in
      the ovine ureter.
AB  - The prostaglandins (PGs) synthesized from C14-arachidonic acid by the homogenized
      sheep ureter were identified as being prostacyclin (PGI2), PGF2 alpha and
      thromboxane B2 (TXB2). The radioimmunoassay (RIA) estimation of 6-keto-PGF1
      alpha, a stable metabolite of PGI2, confirms that it was the major metabolite of
      arachidonic acid. Aqueous extracts of fresh garlic (5, 12.5, 25 and 50 mg/ml)
      were shown to inhibit the synthesis of the prostanoids in a dose dependent
      manner. Fresh garlic extracts (1, 2.5, 5 and 10 mg/ml) also dose dependently
      inhibited spontaneous rhythmic contractions of the isolated ureter. Boiled garlic
      (5, 12.5, 25 and 50 mg/ml) had no effect on either ureteral motility or the PG
      synthesizing capacity of the sheep ureter.

PMID- 8302921
TI  - Inhibitory effect of docosahexaenoic acid-containing phospholipids on 5
      lipoxygenase in rat basophilic leukemia cells.
AB  - 5-Lipoxygenase has been recognized to be an important enzyme that catalyzes the
      first step in leukotriene production. In this study we examine whether or not
      phospholipids containing docosahexaenoic acid (DHA) affect 5-lipoxygenase
      activity of a rat basophilic leukemia cell line (RBL-1). Among the synthesized
      phospholipids examined, 1-oleoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (1
      oleoyl-2-DHA-PC) was found to be the most potent inhibitor of 5-lipoxygenase. The
      inhibition was dose-dependent and the ID50 value was 4.0 microM. When the fatty
      acid at the sn-2-position was replaced by other unsaturated fatty acids, the
      inhibitory activity decreased with decreasing numbers of both carbon atoms and
      double bonds in the fatty acids. Substitution at the 1-position of the DHA
      containing PC also affected the inhibitory potency. If oleic acid was substituted
      with palmitic acid, the inhibition activity was completely abolished. Lineweaver
      Burk plot analysis showed that the inhibition of 5-lipoxygenase by 1-oleoyl-2-DHA
      PC was non-competitive. The inhibition by this synthesized phospholipid was very
      specific to 5-lipoxygenase; that is, it did not extend to fatty acid
      cyclooxygenase, 12-lipoxygenase or 15-lipoxygenase. These results suggest that
      endogenously existing DHA-containing phospholipids may affect 5-lipoxygenase
      activity and thus control leukotriene biosynthesis in vivo.

PMID- 8302922
TI  - Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension.
AB  - To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced
      hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured
      using the heat clearance method in 30 patients who underwent postero-lateral
      interbody fusion under isoflurane anaesthesia. An initial dose of 0.1
      microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP
      (15 patients) was administered intravenously after the dural opening and the dose
      was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg.
      The hypotensive drug was discontinued at the completion of the operative
      procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP)
      decreased significantly compared with preinfusion values (P < 0.01), and the
      degree of hypotension due to PGE1 remained constant until 60 min after its
      discontinuation. Heart rate (HR) did not change in either group. EBFF did not
      change during PGE1 infusion whereas in the TMP group, EBF decreased significantly
      at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min.
      30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P
      < 0.05)). These results suggest that PGE1 may be preferable to TMP for
      hypotensive anaesthesia in spinal surgery because TMP decreased EBF.

PMID- 8302923
TI  - Assessment of the graduates of the selected aspects of competency-based B.S.N.
      curriculum.

PMID- 8302925
TI  - Strengthening nursing and midwifery in support of strategies for health for all.

PMID- 8302924
TI  - A conceptual framework for the integration of primary health care in the BSN
      curriculum.

PMID- 8302926
TI  - Evaluation of the performance of colleges of nursing in the Philippines.

PMID- 8302927
TI  - Comparative analysis of the pC194 group of rolling circle plasmids.
AB  - pC194-type plasmids have been isolated from widely divergent species of bacteria:
      Gram positive, Proteobacteria, Spirochaetes and Cyanobacteria. We have examined
      the three essential replication elements of these plasmids, i.e., the Rep
      protein, and the origins of double and single stranded synthesis. Comparative
      analysis of Rep protein sequences from these plasmids indicates that they are
      highly divergent. Those isolated from Gram positive species fall into five
      groups: a Bacillus group, a Lactobacillus group, a Streptococcus group and two
      Staphylococcus aureus groups. The two S. aureus clusters are quite separate,
      suggesting that there has been at least one plasmid transfer between divergent
      Gram positive species. The double stranded origin of replication and the active
      site of the Rep protein display similarities across species indicating that these
      motifs can function in very divergent hosts. In contrast the single stranded
      origin of replication is typical of the host from which the plasmid is isolated.
      This is exemplified by (i) pKYM where the single stranded origins are similar to
      the minus origins found on the single-stranded coliphages, and (ii) pTD1
      (isolated from a Spirochaete), pNostoc, pMA1 and pRF1 (all isolated from
      Cyanobacteria) which have no sequence homology to the minus origins identified in
      Gram positive or Gram negative species. This points to the single stranded origin
      as a feature critical to the determination of the host range of the plasmid.

PMID- 8302928
TI  - Characterization of the pea chloroplast DNA OriA region.
AB  - One of the two origins of replication in pea chloroplast DNA (oriA) maps in the
      rRNA spacer region downstream of the 16S rRNA gene, and further characterization
      of this origin is presented here. End-labeling of nascent DNA strands from in
      vivo replicating ctDNA was used to generate probes for Southern hybridization.
      Hybridization data identified the same region that was previously mapped to
      contain D-loops by electron microscopy. Subclones of the oriA region were tested
      for their ability to support in vitro DNA replication using a partially purified
      pea ctDNA replication system. Two-dimensional agarose gel electrophoresis
      identified replication intermediates for clones from the region just downstream
      of the 16S rRNA gene, with a 450-bp SacI-EcoRI clone showing the strongest
      activity. The experiments presented in this paper identify the 940 base pair
      region in the rRNA spacer between the 3' end of the 16S rRNA gene and the EcoRI
      site as containing oriA. Previous studies by electron microscopy localized the D
      loop in the spacer region just to the right of the BamHI site, but the
      experiments presented here show that sequences to the left of the BamHI site are
      required for replication initiation from oriA. DNA sequence analysis of this
      region of pea ctDNA shows the presence of characteristic elements of DNA
      replication origins, including several direct and inverted repeat sequences, an A
      + T rich region, and dnaA-like binding sites, most of which are unique to the pea
      ctDNA oriA region when compared with published rRNA spacer sequences from other
      chloroplast genomes.

PMID- 8302929
TI  - Sequence analysis of Leuconostoc oenos DNA: organization of pLo13, a cryptic
      plasmid.
AB  - A Leuconostoc oenos plasmid, pLo13, was studied to analyze its genetic
      organization and to define its functions. The nucleotide sequence (3948 bp)
      revealed three major open reading frames. Features commonly found in plasmids
      that replicate via a rolling-circle mechanism were identified within pLo13:
      first, a sequence coding for a protein with an amino acid sequence homologous to
      the plasmid recombination enzymes (Pre), but for which a specific target site
      similar to those previously described was not found; second, a sequence probably
      encoding a replication protein (Rep). The putative pLo13 Rep protein amino acid
      sequence is divergent from the pC194-pUB110 family Rep proteins. However, the
      consensus sequence of the Rep protein active site was found, as well as the Rep
      protein consensus target site. No sequence similar to the previously described
      minus-origins (SSOs) are present in pLo13; nevertheless, a 200-bp sequence rich
      in imperfect palindromes may be involved in the minus-strand replication. These
      overall differences are in agreement with the previously reported important
      phylogenetic distance existing between Ln. oenos and other lactic acid bacteria.

PMID- 8302930
TI  - Resistance to imidazoles and triazoles in Saccharomyces cerevisiae as a new
      dominant marker.
AB  - The imidazole and triazole fungicides inhibit cytochrome P450 14 alpha-lanosterol
      demethylase (P45014DM) implicated in the ergosterol biosynthesis pathway, which
      is specific to fungi and yeasts. Two plasmids were obtained which allow triazole
      and imidazole resistance in Saccharomyces cerevisiae. The low copy number plasmid
      (pFD 383) encodes cytochrome P450 C14 alpha lanosterol demethylase under the
      control of phospho-glycerate-kinase promoter. S. cerevisiae transformed by the
      pFD 383 plasmid are resistant to imidazoles and triazoles. Moreover, this
      transformed strain shows increased levels of P45014DM mRNA and of cytochrome
      P450. A second low copy number plasmid (pFD 384) carries a mutant cytochrome P450
      14 alpha lanosterol demethylase gene, which increases imidazole and triazole
      resistance. These constructions can be used on a dominant selection marker to
      transform wild-type yeasts and to confer imidazole and triazole resistance in
      industrial fermentation.

PMID- 8302931
TI  - Characterization of the left 4 kb of conjugative transposon Tn916: determinants
      involved in excision.
AB  - The rate-limiting step in movement of the conjugative transposon Tn916,
      originally identified in Enterococcus faecalis, is believed to be an excision
      event that generates a non-replicative circular intermediate. When present on a
      plasmid vector in Escherichia coli, Tn916 generally excises at a high frequency.
      It was reported previously that insertion of Tn5 in a region near the left end of
      Tn916 eliminated the ability to excise; and the mutation could be complemented in
      trans. In this communication the nucleotide sequence of 4 kb of Tn916 DNA
      connecting the recently sequenced tet(M) determinant (Su et al., 1992; Burdett,
      1990) with the left end of the transposon. Ten open reading frames (ORFs) were
      deduced, two of which (ORF3 and ORF4) were encoded in-frame within a third
      (ORF2). Mutants with Tn5 insertions in the ORF1 or ORF2 (ORF3 and ORF4) were
      defective in excision, but could be complemented in vivo by a co-resident plasmid
      containing the ORF1 or ORF2 determinant, respectively. The data support the view
      that both ORF1 and ORF2 are essential for excision. ORF1 and ORF2 are essentially
      identical to determinants designated xis-Tn and int-Tn, respectively, in the
      closely related Tn1545. A Tn5 insertion in ORF5 eliminated conjugative transfer
      between E. faecalis strains. Functions for the remaining ORFs (ORF6 through
      ORF10) remain unknown; however, nucleotide sequences within ORF6 and ORF9 had
      significant homology with sequence downstream of other tet(M) determinants.

PMID- 8302932
TI  - Movement of shuttle plasmids from Escherichia coli into yeasts other than
      Saccharomyces cerevisiae using trans-kingdom conjugation.
AB  - Transfer of bacteria/yeast shuttle plasmids from Escherichia coli into the yeast
      species Kluyveromyces lactis, Pichia angusta (Hansenula polymorpha), and
      Pachysolen tannophilus has been accomplished, presumably through inter-kingdom
      conjugal transfer. Plasmid pEK2 was transferred into a K. lactis mutant to
      complement trp auxotrophy, while plasmid YEp13 was mobilized into and
      complemented P. angusta and P. tannophilus Leu- auxotrophs. Plasmid DNA in the
      recipient strains was detected by transformation of E. coli with crude yeast cell
      extracts. Freely replicating plasmids without detectable alterations as well as
      plasmids with rearrangements were recovered from yeast transconjugants.

PMID- 8302933
TI  - Characterization of the small cryptic plasmid, pIMVS1, of Salmonella enterica
      ser. Typhimurium.
AB  - The nucleotide sequence has been determined of a small cryptic plasmid of
      Salmonella Typhimurium, designated pIMVS1, which correlated with an outbreak of
      gastroenteritis. This plasmid has a size of 3357 bp with no known functions. It
      does not encode any protein products but shows homology to several well
      characterized plasmids. The replication system with RNAI and RNAII and the
      replication origin (oriV) is highly similar to that of plasmid p15A. It also has
      a putative mobilisation origin similar to that of ColE1.

PMID- 8302934
TI  - Construction of a shuttle vector for use between Pasteurella multocida and
      Escherichia coli.
AB  - The isolation of a small plasmid from Pasteurella multocida has enabled the
      construction of a shuttle vector for use between P. multocida and Escherichia
      coli. The vector pBAC64 contains the origin of replication from P. multocida, an
      antibiotic resistance gene which functions in P. multocida, and the E. coli
      vector pUC18. The presence of the pUC18 multiple cloning site together with the
      lacZ' gene provides a screening method and allows cloning and manipulation in E.
      coli as well as cloning in P. multocida.

PMID- 8302935
TI  - pClK1 and pClT5--two linear mitochondrial plasmids from unrelated Claviceps
      purpurea strains: a comparison.
AB  - pClT5, a linear mitochondrial (mt) plasmid from Claviceps purpurea, strain T5,
      was sequenced and compared to pClK1, a linear mt plasmid from an unrelated C.
      purpurea strain. Both plasmids have terminal proteins (TPs) at their inverted
      terminal repeats (TlR). The TlRs of both plasmids show short conserved sequences,
      which are probably involved in plasmid transcription and replication. The coding
      capacity of pClT5 and pClK1 is similar: there are two large ORFs (ORF1 and ORF2)
      homologous to the DNA and RNA polymerase ORFs of pClK1 and several small
      hydrophobic ORFs. ORF3 shows homology to a small ORF of the Neurospora crassa mt
      plasmid maranhar and is transcribed. ORF6 of pClT5 is homologous to ORF4 of
      pClK1; both are transcribed and are possible candidates for the TP encoding ORF.

PMID- 8302936
TI  - Physical characterization of plasmid pMQV10 from a steroid biotransforming strain
      of Micrococcus.
AB  - The presence of a single plasmid 8.5 kb in size has been demonstrated in a
      cholesterol biotransforming strain of Micrococcus. A detailed physical map of the
      plasmid has been constructed using various restriction enzymes. Streptomycin
      resistance has been localized on a 1.8-kb fragment of pMQV10.

PMID- 8302937
TI  - Expression of a synthetic DNA region containing a consensus promoter and two lac
      operators in Brevibacterium sp.
AB  - The cat reporter gene was used to assess expression of two promoters, previously
      strongly expressed in Escherichia coli, in Brevibacterium sp. R312 strain. The
      tac promoter (de Boer et al., 1983, Proc. Natl. Acad. Sci. USA 80, 21-25) was
      poorly expressed in Brevibacterium sp. In contrast, the AatII-SalI fragment of
      plasmid pYEJ001 (Pharmacia LKB Biotechnology, Sweden) containing two lac
      operators, a consensus sequence promoter and the cat structural gene clearly
      revealed chloramphenicol acetyltransferase activity and the presence of a 25,600
      kDa protein, corresponding to the monomeric CAT protein, in cell extracts.

PMID- 8302938
TI  - Development of a genetic system for Eikenella corrodens: transfer of plasmids
      pFM739 and pLES2.
AB  - Eikenella corrodens is a Gram-negative microaerophilic rod which is emerging as
      an important human pathogen. Elucidation of the mechanisms by which it causes
      disease require efficient methods for the transfer of DNA to E. corrodens.
      Plasmids pFM739 and pLES2 have been transferred by conjugation from Escherichia
      coli S17-1 to E. corrodens ATCC 23834 at frequencies of 2.5 x 10(-7) and 2.42 x
      10(-7), respectively. In addition, both plasmids could be transferred to four
      additional, clinical strains of E. corrodens at a similar frequency. The use of
      bacteriophage T4 as a counterselecting agent is also described.

PMID- 8302939
TI  - Identification and characterization of a mobilization gene in the streptococcal
      plasmid, pVA380-1.
AB  - The 4.2-kb cryptic streptococcal plasmid, pVA380-1, has a broad host range and
      replicates via a rolling circle mode. The nucleotide base sequence of the 2.5-kb
      basic replicon of this plasmid, containing a plus origin, a minus origin, and a
      rep gene, was reported previously. The completed nucleotide base sequence of
      pVA380-1 revealed the presence of two additional open reading frames, ORF2 and
      ORF3. The protein predicted by ORF2 shared 74% amino acid identity with the Mob
      protein of the Group B streptococcal plasmid, pMV158. The 170 bases immediately
      5' to ORF2 and to mob of pMV158 shared 87% homology and included a putative -10
      region and a RSa site. A derivative of pVA380-1 into which a kanamycin resistance
      gene was inserted outside of the above 170 base region and ORF2 was mobilized by
      the conjugative streptococcal plasmid, pAM beta 1, into Enterococcus faecalis and
      Streptococcus sobrinus. Interruption of ORF2 by the same kanamycin resistance
      gene abolished the mobilizability of pVA380-1.

PMID- 8302940
TI  - Molecular characterization of an aberrant mercury resistance transposable element
      from an environmental Acinetobacter strain.
AB  - We present the complete nucleotide sequence of a mer operon located on a 60-kb
      conjugative plasmid pKLH2 from an environmental bacterium, Acinetobacter
      calcoaceticus, isolated from a mercury mine. The pKLH2 mer operon has essentially
      the same gene organization as that of Tn21 and Tn501 from clinical bacteria. The
      pKLH2 mer operon nucleotide sequence shows 85.5% identity with the Tn501 and
      80.9% identity with the Tn21 sequences. Vestigial sequences have been found at
      the ends of the pKLH2 mer operon, indicating that the pKLH2 mer operon was once a
      part of a Tn21-like transposon, which had committed suicide by an aberrant
      resolution event.

PMID- 8302941
TI  - Restriction map of a virulence-associated plasmid of Rhodococcus equi.
AB  - The restriction cleavage map of a virulence-associated plasmid pREAT701 of
      Rhodococcus equi was constructed with EcoRI and HindIII by means of cloning the
      restriction fragments, cross Southern hybridization with each fragment, and
      hybridization with probes generated by modified inverse PCR. The genetic region
      responsible for expression of virulence-associated 15- to 17-kilodalton antigens
      was determined.

PMID- 8302942
TI  - A useful cloning vector for Bacillus subtilis.
AB  - We have constructed plasmid pDN1050, a new small cloning vector for Bacillus
      subtilis. pDN1050 harbors the origin of replication of Staphylococcus aureus
      plasmid pUB110 and the chloramphenicol resistance gene of S. aureus plasmid
      pC194. The plasmid is segregationally and structurally stable. Plasmid pDN1370, a
      low copy number mutant of pDN1050 was isolated and shown to harbor a mutation in
      the repA gene of the replication protein.

PMID- 8302943
TI  - Abietane acids: sources, biological activities, and therapeutic uses.
AB  - The biological activities of natural abietane acids and their derivatives have
      been reviewed from 1967 to 1992. Antimicrobial, antiulcer, and cardiovascular
      activities are the most representative for this class of diterpenoids, while
      others like allergenic, antiallergic, filmogenic, surfactant, antifeedant, etc.
      activities, which determine several uses of abietane acids, have also been
      reported.

PMID- 8302944
TI  - Metabolism of caffeic acid in the isolated perfused rat liver.
AB  - Caffeic acid as well as its oxidation products exert a spectrum of biological
      effects in in vitro testing. To get an idea of the amount as well as the mode of
      biotransformation, caffeic acid metabolism was investigated by means of the
      isolated perfused rat liver. The first-pass effect was not pronounced: 93.3% of
      caffeic acid dose appeared unchanged after one liver passage. Products of caffeic
      acid oxidation (cyclolignan derivatives) as well as ferulic and isoferulic acid
      as methylation products were found in the perfusion medium. In addition, a
      cyclization product, esculetin, was observed. In the bile, mainly glucuronides as
      well as sulfates of caffeic acid could be determined. Thus, oxidation products
      and other metabolites formed by liver metabolism can be responsible for the
      biological effects in vivo.

PMID- 8302945
TI  - Gastro-protective effects by extracts of Petasites hybridus: the role of
      inhibition of peptido-leukotriene synthesis.
AB  - Extracts from Petasites hybridus are in therapeutic use for more than 2000 years.
      They have been claimed to improve gastrointestinal pain, lung-diseases such as
      asthma and cough, as well as spasms of the urogenital-tract. We have investigated
      these claims in animal models of gastro-intestinal ulcers and confirmed that
      alcoholic extracts of Petasites hybridus block the ethanol-induced gastric damage
      and reduce small intestinal ulcerations induced in rats by indomethacin.
      Searching for a possible mode of action, we found that ethanolic extracts of
      Petasites hybridus inhibit the peptido-leukotriene biosynthesis in mouse
      peritoneal macrophages but leave prostaglandin biosynthesis unimpaired. We
      conclude that the active principle could be useful in the treatment of gastro
      intestinal human diseases and that Petasites hybridus may contribute to the
      inhibition of calcium-dependent processes such as leukotriene biosynthesis.

PMID- 8302946
TI  - Gastroprotection and prostaglandin E2 generation in rats by flavonoids of
      Dittrichia viscosa.
AB  - Investigations were carried out to determine the gastroprotective effects of the
      flavonoid fraction of Dittrichia viscosa (L.) W. Greuter against gastric lesions
      produced by necrotizing agents. The action of the fraction on the production of
      mucus, and the involvement of endogenous PGs in gastric mucosal defensive
      mechanisms were also determined. Gastric ulcers induced by oral administration of
      three necrotic agents (100% ethanol, 0.6 N HCl, 30% NaCl) were markedly reduced
      by pretreatment with the flavonoid extract at doses from 125 to 500 mg/kg p.o.
      and the reduction at the highest dose (500 mg/kg p.o.) was practically complete.
      Flavonoid fraction pretreatment also increased mucus production and glycoprotein
      content. In addition, intraperitoneal administration of indomethacin (10 mg/kg
      i.p.) to animals treated with the extract (500 mg/kg) partially inhibited gastric
      protection but the PGE2 determination did not show an increase in prostanoid
      level. These observations suggest that the gastroprotective effects of the
      flavonoid fraction from D. viscosa could be partly explained through non
      prostaglandin-dependent mechanisms.

PMID- 8302947
TI  - Inhibition of mutagenicity in Salmonella typhimurium by Glycyrrhiza glabra
      extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids.
AB  - The effects of Glycyrrhiza glabra L. extract, glycyrrhizinic acid, 18 alpha- and
      18 beta-glycyrrhetinic acids on the mutagenicity of the ethyl methanesulfonate, N
      methyl-N'-nitro-N-nitrosoguanidine, and ribose-lysine Maillard model systems were
      investigated by using the Salmonella/microsome reversion assay. The protocol used
      allowed us to detect desmutagenic and antimutagenic activity and to avoid false
      positive results due to toxicity. For all the compounds tested, no desmutagenic
      activity was observed against ethyl methanesulfonate and N-methyl-N'-nitro-N
      nitrosoguanidine; only Glycyrrhiza glabra extract showed antimutagenic activity
      against ethyl methanesulfonate. On using the ribose-lysine mutagenic browning
      mixture, the desmutagenic activities of the Glycyrrhiza glabra extract,
      glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids were observed. 18
      beta-Glycyrrhetinic acid was the most active compound. Glycyrrhiza glabra extract
      also exhibited antimutagenic activity against ribose-lysine.

PMID- 8302948
TI  - Antilipolytic action of hesperetin in rat adipocytes.
AB  - Hesperetin was able to inhibit both epinephrine- and theophylline-induced
      lipolysis in rat adipocytes. At concentrations of 125 microM and 250 microM, it
      could augment the inhibitory effect of low insulin concentration (17 microU/2ml)
      on epinephrine-induced lipolysis. The basal cyclic AMP levels and
      phosphodiesterase activities in intact adipocytes were unaltered by hesperetin.
      The antilipolytic action of hesperetin in adenosine deaminase pretreated
      adipocytes was abolished. Hesperetin could only prevent lipolysis but not reverse
      the initial lipolytic activity stimulated through the adenosine deaminase
      pretreatment of the adipocytes. In pertussis or cholera toxin (PT or CT)
      pretreated adipocytes, the antilipolytic action of hesperetin was unaffected.
      From the data obtained it is possible to conclude that the antilipolytic action
      of hesperetin is not mediated through the inhibition of cyclic AMP level nor
      through CT- or PT-sensitive G proteins. However, the involvement of hesperetin in
      preventing the accessibility of cellular receptors to the actions of lipolytic
      agents may be implicated.

PMID- 8302949
TI  - Antitumor activity of Parthenium hysterophorus and its effect in the modulation
      of biotransforming enzymes in transplanted murine leukemia.
AB  - The methanolic flower extract of Parthenium hysterophorus has been found to have
      antitumor effects in host mice bearing transplantable lymphocytic leukemia. The
      effect was more pronounced in terms of tumor size, tumor spread, and survival of
      the host. The potentiating effect of the extract was supported by biochemical
      autopsies relating to markers like glutathione level, cytochrome P-450 content,
      glutathione transferase, and UDP-glucuronyl transferase in liver tissue of the
      host cells. These neoplastic markers showed substantial alteration leading to
      slow development of tumors and increased survival of the host bearing lymphocytic
      leukemia.

PMID- 8302950
TI  - Bioactive compounds from the buds of Platanus orientalis and isolation of a new
      kaempferol glycoside.
AB  - A new compound kaempferol 3-O-alpha-L-(2"-E-p-coumaroyl)-rhamnopyranoside, as
      well as the known flavonoids, kaempferol 3-O-beta-D-(6"-E-p-coumaroyl)
      glucopyranoside, kaempferol 3-O-alpha-L-(2",3"-di-E-p-coumaroyl)
      rhamnopyranoside, and caffeic acid were obtained from the methanolic extract of
      Platanus orientalis L. buds. All the compounds were isolated by column
      chromatography and identified using 1H-NMR, 2D-1H-NMR (COSY), 1H-13C-NMR, and
      CIDMS techniques. Cytotoxic and antimicrobial studies were carried out in vitro
      against human cell lines and against Gram-positive and Gram-negative organisms.

PMID- 8302951
TI  - Inhibition of autochthonous tumor by ethanol insoluble fraction from Panax
      ginseng as an immunomodulator.
AB  - The water extract of Panax ginseng was fractionated by its solubility in ethanol
      and then the ethanol-insoluble fraction was tested for immunomodulatory activity.
      The ethanol-insoluble fraction of ginseng (Fr. 3) proliferated splenocytes and
      generated activated killer cells in vitro. These activated killer cells killed
      both NK cell sensitive and insensitive tumor target cells without MHC
      restriction. Activation of splenocytes by ginseng was mediated through the
      endogenously produced IL-2. To investigate the effects of Fr.3 on the
      autochthonous neoplasm, a single subcutaneous injection of 0.5 mg of
      benzo[a]pyrene (BP) was given within 24 hours after birth of male N: GP(S) mice,
      and Fr.3 was administered in drinking water at a concentration of 2 mg/ml, 1
      mg/ml, or 0.5 mg/ml for 6 weeks after weaning. The treatment with Fr. 3
      significantly inhibited lung tumor incidence (P < 0.05) compared with the BP
      alone group at a concentration of 2 mg/ml or 1 mg/ml in drinking water at the 9th
      week after BP treatment. These results suggest that the ethanol-insoluble
      fraction of ginseng shows antitumor effects as an immunomodulator.

PMID- 8302952
TI  - Inhibitory effect of the water extract of spikes of Miscanthus sinensis on IgE
      formation in mice.
AB  - The effects of four different plant extracts of the spikes of Miscanthus
      sinensis, Phragmites communis, and Imperata cylindrica var. major, and of the
      spikelets of Coix lachryma-jobi on IgE antibody formation were investigated in
      mice. The IgE antibody titer was tested by the passive cutaneous anaphylaxis
      (PCA) method in rats. Of these, the water extract of M. sinensis showed an
      appreciable inhibitory effect on IgE formation. Furthermore, an undialyzable
      fraction of the water extract with a relative molecular mass of more than 50,000
      d, designated as MSIS, showed the most potent inhibitory activity on IgE
      formation. MSIS was also a potent inhibitor of IgE formation when given
      intraperitoneally or intranasally to mice the day before injection of
      dinitrophenyl (DNP)-ovalbumin (OVA) antigen in both the primary and secondary
      immune responses. Moreover, MSIS clearly suppressed on-going IgE antibody
      formation in both primary and secondary immune responses.

PMID- 8302953
TI  - Anti-inflammatory activity of the essential oil of Bupleurum fruticescens.
AB  - The essential oil of Bupleurum fruticescens was investigated qualitatively and
      quantitatively by GC and GC-MS analyses. The anti-inflammatory activity of the
      whole essential oil and its major components was also investigated in the rat
      hindpaw edema model induced by carrageenin or by PGE1. The anti-inflammatory
      activity shown by the essential oil can be attributed to the two major
      components, alpha-pinene and beta-caryophyllene. In order to know the role of the
      adrenal glands in the anti-inflammatory activity exerted by the two major
      components of the essential oil, they were studied against the carrageenin
      induced hindpaw edema in adrenolectomized rats. It is concluded that alpha-pinene
      needs the integrity of the adrenal glands to exert its anti-inflammatory
      activity, as opposed to beta-caryophyllene which was also active in
      adrenolectomized animals.

PMID- 8302954
TI  - Cardiac glycosides in partly submerged shoots of Digitalis lanata.
AB  - Shoot cultures were established from axillary buds (11 strains) or seeds (1
      strain) of individual Digitalis lanata Ehrh. plants and propagated partially
      submerged in liquid medium. Five of these shoot culture strains were
      characterized with regard to their growth and cardenolide content. The cultures
      were observed for more than one year and found to be relatively stable with
      regard to their growth and cardenolide spectrum and yield. The strains examined
      differed in terms of their total cardenolide yield, which ranged from about 30
      nmol g DW-1 to almost 1000 nmol g DW-1. Cardenolide content was correlated with
      leaf size and development. Depending on the strain investigated up to ten
      different cardenolides could be detected by HPLC. The main cardenolides were
      identified by comparing HPLC and TLC results with those of authentic samples and
      chemical degradation as being the mono- and diglycosides glucodigifucoside,
      glucoverodoxin, odorobioside G, and odoroside H; minor amounts of digitalinum
      verum and glucoevatromonoside were also found. In addition, the tetrasaccharides
      lanatoside A and C were present. The shoots were cardenolide-free when cultivated
      in the dark for more than 30 weeks, but regained their characteristic cardenolide
      profile when transferred back to light. For the dark cultivation of chlorophyll
      free cultures a medium containing 3.5% glucose was found to be optimal.

PMID- 8302955
TI  - Five new prenylated p-hydroxybenzoic acid derivatives with antimicrobial and
      molluscicidal activity from Piper aduncum leaves.
AB  - Five new prenylated benzoic acid derivatives, methyl 3-(3,7-dimethyl-2,6
      octadienyl)-4-methoxybenzoate (1), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5
      bis(3-methyl-2-butenyl)-4-hydroxybenzoate (2), 1-(1-methylethyl)-4-methyl-3
      cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (3), methyl 3,5-bis(3
      methyl-2-butenyl)-4-methoxybenzoate (4), and 4-hydroxy-3-(3-methyl-2-butenyl)-5
      (3-methyl-2-butenyl)-benzoic acid (5) were isolated from the dried leaves of
      Piper aduncum L. (Piperaceae). Together with the new metabolites, four known
      prenylated benzoic acid derivatives, 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic
      acid (6), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (nervogenic acid,
      7), methyl 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoate (8), and methyl 4
      hydroxy-3-(3-methyl-2-butenyl)-benzoate (9) as well as, dillapiol (10),
      myristicin, and the three sesquiterpenes humulene, caryophyllene epoxide, and
      humulene epoxide were isolated. Compounds 7, 8, and 9 are reported as natural
      products for the first time. The structures of the isolates were elucidated by
      spectroscopic methods, mainly 1D-and 2D-NMR spectroscopy. Isolates 4-7, 9, and 10
      were molluscicidal while 2, 5-7, and 9 displayed significant antibacterial
      activities.

PMID- 8302956
TI  - Studies on the constituents of Tinospora sinensis; I. Separation and structure of
      the new phenolic glycoside tinosinen.
AB  - A new phenolic glycoside, tinosinen (1), was isolated from the fresh stems of
      Tinospora sinensis Merr. The structure was established on the basis of acid
      hydrolysis and spectral data (IR, NMR, mass) as (E)-1-(3-hydroxy-1-propenyl)-3,5
      dimethoxyphenyl 4-O-beta-D-apiofuranosyl-(1-->3)-beta-D-glucopyranoside.

PMID- 8302957
TI  - Akuammine: an antimalarial indolemonoterpene alkaloid of Picralima nitida seeds.

PMID- 8302958
TI  - Rhazimine from Rhazya stricta: a dual inhibitor of arachidonic acid metabolism
      and platelet activating factor-induced platelet aggregation.

PMID- 8302959
TI  - Isolation of antihypertensive alkaloids from the rhizomes of Veratrum album.

PMID- 8302960
TI  - Blood pressure responses to an extract of Ajuga remota in experimentally
      hypertensive rats.

PMID- 8302961
TI  - [Continuing education and certification system in psychiatry].

PMID- 8302963
TI  - [Point of contact between psychopathology and biological psychiatry].

PMID- 8302962
TI  - [Psychopathology and biological psychiatry].

PMID- 8302964
TI  - [Point of contact between psychopathology and biological psychiatry].

PMID- 8302965
TI  - [A family study of affective disorders].

PMID- 8302966
TI  - [Early infantile autism: from a psychoanalytic point of view in 1993].
AB  - The syndrome of early age autism sets in during the first two years of life.
      Various theories have been developed on the basis of etiological hypotheses
      postulating the occurrence of an accident in the psychic development of the
      infant. According to their personal theoretical orientation, authors have
      formulated the consequences of this accident in terms of a deficit or a
      regression. The author investigates various contexts in which the syndrome
      develops before continuing on its own. Outcomes are also diverse and do not seem
      to be always linked to the initial modes of organization, therefore raising some
      therapeutical questions.

PMID- 8302967
TI  - [Infantile autism, psychoanalytic research and scientific status].
AB  - After emphasizing the very modern aspect of psychoanalytic epistemology, the
      author shows how psychoanalytical research applied to the issue of infantile
      autism concentrates the maximum of difficulties and is therefore vulnerable to
      critics from the "hard" sciences. Some tentative answers are proposed in
      reference to the narrative sciences. The author then suggests various tracks for
      the psychoanalytical research in the field of infantile autism.

PMID- 8302968
TI  - [Dysphonetic dyslexia and semantic path].
AB  - The author formulates the core question of the research in some severe forms
      reading disturbances in children. The aim is to develop a model at the interface
      between the cognitive approach and the affective approach so as to analyze the
      different elements of the global strategy adopted by some children diagnosed as
      "dysphonetic dyslexics" when confronted with written material. The author defines
      the theoretical and methodological prerequisites that are necessary for such a
      clinical investigation focused on a symptom.

PMID- 8302969
TI  - [Linguistic thinking disorders, dysphasia, and quality of life].
AB  - This study focuses on the nature and scope of thought disturbances in dysphasic
      children (age 6 to 10). It is a developmental and clinical study. The dysphasic
      child clearly manifests disturbances in language. These can be understood as
      disturbances of the linguistic "containers of thought". What impact do they have
      on the development of cognitive and affective experiences? A controlled study of
      logical operations involving reversibility and invariates shows some significant
      differences between dysphasic children and a matched group of non patient
      children. Findings, both, quantitative and qualitative, point to some specific
      difficulties in the acquisition of operative (in Piaget sense) structures of
      thought. Often regarded as "practical persons" dysphasic children manifest
      peculiar ways of integrating their affective experiences in a factual mode akin
      to alexithymia. Linguistic anomalies seem to be important elements of some
      complex "noeto linguistic" disturbances. Linguistic difficulties have a global
      impact on the quality of life of dysphasic children and need further
      investigation for developing relevant intervention programs.

PMID- 8302970
TI  - [Interactive capacities of children aged 4 to 7 months with a child of the same
      age].
AB  - In this article we report on the first results of a research on the abilities and
      interactive behaviors of 16 infants aged from 4 to 7 months, with an infant of
      the same age. These infants are studied in dyads from the moment they are seated
      by their mother in two experimental seats. The position and distance of the seats
      are regulated at distance according to a procedure consisting in 8 phases of 3
      minute duration each. The mothers of the two infants are present and can be seen
      by their child during the experimental session. The principal results can be
      summed up as follows: 1. The infant-partner is the first rank target of the gaze
      of the other infant. The frequency and duration of the orientations of the gaze
      in the direction of one or another of its body areas are significantly higher
      than the frequency and duration of the self-centered gazes (very weak) and the
      frequency and duration of the orientations of the gaze in other directions,
      including towards their mothers. These behaviors between the infants do not
      decrease in frequency or duration as long as the infants do not receive an
      object. 2. The face and hands of the infant-partner are the most frequent targets
      of the gaze; they also have the highest cumulated duration. The mutual catching
      of the eyes is also well represented, since this occupy the fifth place among the
      25 items of behavior which were measured. 3. 4 of the 7 best represented items
      are the interactive behaviors with the other infant. 4. The manual behaviors
      already appear well organized, targetted, and visually controlled. In particular:
      the extension of the arm in the direction of the infant-partner, with the hand in
      pronation, lateral, oblique or in supination; the extension of the arm with a
      rotation of the hand from the pronation position to the supination position;
      taking the hand of the other infant. 5. Among the other complex behaviors one can
      observe diverse forms of imitation and modulated vocalizations which are rich in
      phonemes. 6. Most interactive behaviors are influenced by the human context (the
      different positions of the infants with regard to each other) and giving an
      object to each infant (last phase of the protocol). The infants appear,
      therefore, capable of taking into account most behaviors of the other infant in
      the organization of their own behaviors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8302971
TI  - [The stomach speaks: chronicle of a deadly boredom].
AB  - The author describes the evolution of the psychotherapy of an 11 year old child:
      starting with an anonymous depression related to diffuse somatic complaints, it
      evolved into a playful assertion of a self which seems to depart from the family
      destiny. The author describes his counter-transferential feelings of tiredness
      and boredom which were compensated by a constant complicity with his young
      client. The author suggests that it is this very act of supporting the assertion
      and formulation of the subject, and disregarding unconditionally the boredom of
      what is said, which has brought about such a striking and sudden change.

PMID- 8302972
TI  - [The vicissitudes of the therapeutic alliance or going from childhood to
      adolescence during psychotherapy].
AB  - By tracking the modifications of the therapeutic alliance between a pre
      adolescent boy and his therapist, the author attempts 1/to describe the
      differences in terms of techniques and goals between low frequency session
      therapies and intensive therapies, and 2/to outline some of the characteristics
      of the psychic functioning of this age. In this particular case going form the
      first demand to the desire to end therapy, from sessions given on demand to more
      regular sessions, the transference evolved from a narcissic type to an oedipal
      type, heterosexual and homosexual. Some typical conflict of the age has emerged:
      mourning of childhood and anticipation of adolescence in its physical, relational
      and psychic implications. In elaborating this temporal dimension, the child
      develops, with the decline of the Oedipus complex, a cathexis of a personal
      historical space. This cathexis is a crucial process and facilitates the going
      through adolescence.

PMID- 8302973
TI  - [Concerning the notion of the therapeutic alliance during the end of the latency
      period].

PMID- 8302974
TI  - A psychosocial study of albinism in a predominantly Mulatto Caribbean community.
AB  - Psychosocial data collected from 12 albinos in rural and isolated parts of the
      Dominican Republic suggest a stigma is associated with the absence of skin color.
      The general population living in the area has a skin pigmentation of dark brown.
      The purpose of the investigation was to assess whether there were psychosocial
      problems for albinos with white skin and hair. Prior studies imply albinism is a
      negative social characteristic associated with prejudice and apartheid in a
      predominantly mulatto community. This researcher recommends that psychologists
      and health-care providers be familiar with similar sensitive issues among special
      populations.

PMID- 8302975
TI  - Psychometric properties of scales for the measurement of psychosocial variables
      associated with depression in adolescence.
AB  - In preparation for a community-based study of depression in adolescence, several
      point studies were conducted with samples of adolescents. The purpose of these
      studies was to evaluate the reliability and association with depression of
      several instruments when used with older (14- to 18-year-old) adolescents. These
      instruments included measures of cognitions, body image, self-esteem, self
      awareness, social interactions with peers and family, social support, micro- and
      macrostressful life events, anxiety and tension, positive affect, antisocial or
      oppositional behaviour, suicidal ideation, and vocabulary. The internal
      consistency reliability and stability of most of the instruments were
      satisfactory. In addition, most instruments were associated with a measure of
      depression, Radloff's Center for Epidemiological Studies-Depression Scale.
      Several of the scales were successfully abbreviated using techniques based on
      factor analysis and item analysis.

PMID- 8302976
TI  - The nature of stress in child-abusing families: a factor analytic study.
AB  - An instrument for measuring stress (the Family Inventory of Life Events and
      Changes: FILE) was administered to 151 parents of abused children. A factor
      analytic treatment of the results indicated that ten different aspects of stress
      (factors) best explained the data. Several of these factors seemed to be unique
      to the abusing environment while the rest were similar to those found in less
      atypical samples. The results suggest that (a) "local factor analyses" should be
      employed with atypical samples and (b) both measures of types of stress as well
      as general stress may be useful. The ten stress factors identified were (1)
      Trouble with Teenagers, (2) Violence and Separation, (3) Legal Violations, (4)
      Work, (5) Family Loss, (6) Financial Strains, (7) Illness and Family Care
      Strains, (8) Public Assistance, (9) Major Changes in Family Situation, and (10)
      Young Child Management Focus. The "unique" factors that only appeared in our
      child-abusing sample were (1) Trouble with Teenagers, (2) Violence and
      Separation, and (8) Public Assistance.

PMID- 8302977
TI  - Rational behavior training effectiveness for white and nonwhite incarcerated
      felons.
AB  - 45 incarcerated male felons in a medium-security state correctional institution
      participated in a Rational Behavior Training treatment outcome study. 58% of the
      subjects were white, 18% were African-American, 17% were Hispanic, and 7% were
      classified as other. Subjects were selected from an institutional group-therapy
      waiting list and randomly assigned to one of four group facilitators. The Novaco
      Provocation Inventory, Buss-Durkee Hostility Inventory, and Rational Behavior
      Training Concepts Test were administered before and after the 10-wk. treatment
      period. No differences in gain scores (pretest minus posttest) were observed
      although the slightly greater improvement on the concepts test by subjects of
      ethnic minority encourages further study.

PMID- 8302978
TI  - Simple regression-based procedures for taxometric investigations.
AB  - Certain theories of psychopathology postulate the existence of distinct latent
      populations of individuals. By analogy with biology, we call such latent
      populations "taxa" and we call the statistical testing of such theories
      "taxometrics." Taxometric procedures are robust; they do not make restrictive
      distributional assumptions. However, they have two disadvantages for
      nonstatistician users: (1) they are developed via algebra hard for many
      nonstatistician users intuitively to accept; and (2) computational software is
      not widely available. We address these problems by presenting a simple taxometric
      procedure, MAXSLOPE, based on regression plots for pairs of variables. This
      procedure is easily implemented using commonly available software and is
      intuitively rather easy to understand. We apply it to two artificial datasets.
      One dataset, used to explain the graphs, shows clear-cut evidence of taxa. The
      other example shows less clear grouping structure and is used to show that the
      proposed graphical procedure works even in nonideal cases. Comparisons are made
      with currently used procedures of cluster analysis and multivariate normal
      mixture analysis.

PMID- 8302979
TI  - Self-defeating personality: is there a secondary gain?

PMID- 8302980
TI  - Cluster analysis of MMPI scales of patients involuntarily committed for chemical
      dependency treatment.
AB  - This study investigated empirical clusters of MMPI scale T scores for 186 men and
      112 women involuntarily committed to a chemical dependency unit of a state
      psychiatric hospital. Ward's method of cluster analysis produced six clusters
      which were similar to those reported in other cluster-analytic studies of
      alcoholics but with a prominent increase in Scale 6 elevations. Average profiles
      for the six clusters were Spike 6, 6-2-8-4, within normal limits (Clusters 3 and
      4), and 2-6-8-3-4-1-9. Results are discussed in terms of treatment planning for
      this population.

PMID- 8302981
TI  - Anxiety, cognitive interference, and school performance of Italian children.
AB  - The relationship between test-anxiety and school performance is thought to be
      mediated by stress of cognitive appraisal and interference. Worry appears to be
      the critical component of test-anxiety which affects task performance done in the
      USA. The present goal was to investigate relationships among cognitive
      interference, test-anxiety, and school performance of Italian children, 11 to 13
      years old (150 boys, 150 girls). The results show that prior findings are
      applicable to the Italian youngsters, namely, that cognitive interference is
      positively related to test-anxiety and both are related to school performance.

PMID- 8302982
TI  - Nicotine fading and smokeholding methods to smoking cessation.
AB  - We tested a multicomponent behavioural package to stop smoking that contained
      nicotine fading and smokeholding techniques. 73 smokers were randomly assigned to
      one of five treatment programmes: (1) nicotine fading and cigarette fading, (2)
      nicotine fading and concurrent smokeholding, (3) nicotine fading and subsequent
      smokeholding, (4) a nonintensive smokeholding programme, and (5) an intensive
      smokeholding programme (daily sessions). Common components of the programmes were
      self-monitoring, information on smoking, stimulus control, CO feedback, and
      strategies to avoid withdrawal symptoms. Each treatment was carried out during a
      total of 10 sessions over 4 weeks (Treatments 1-4) or 2 weeks (Treatment 5). End
      of-treatment quit rates ranged from 85% to 91%. At 12-mo. follow-up, the most
      effective package proved to have been nicotine fading and cigarette fading, with
      an abstinence rate of 57% as against 25 to 37% for the other treatments.

PMID- 8302983
TI  - Undergraduate adjustment to college, drinking behavior, and fraternity
      membership.
AB  - This study examined the relationship between adjustment to college as measured by
      Baker and Siryk's 1986 Student Adaptation to College Questionnaire, drinking
      patterns, and various aspects of student life (e.g., fraternity or sorority
      membership). A total of 114 students participated. Pearson product-moment
      correlations indicated several significant relationships.

PMID- 8302984
TI  - Psychophysiological activation, reactivity, and recovery in Type A and Type B
      scorers when in a stressful laboratory situation.
AB  - 21 university students participated in a study to assess intergroup differences
      in psychophysiological activation, reactivity, and recovery. Findings support the
      hypothesis that 12 Type A scorers showed a greater activation and reactivity than
      the 9 Type B scorers. Type A scorers needed more time to recover normal
      psychophysiological levels than Type B scorers. We propose that the "fast
      activation-slow recovery" profile is characteristic of Type A scorers. The "fast
      activation-fast recovery" profile is characteristic of Type B-scoring college
      students.

PMID- 8302985
TI  - Sexual abuse prevention programs for preschool children: what do parents prefer?
AB  - Using structured interviews, 21 parents of preschool children at a suburban day
      care center were introduced to the problem of child sexual abuse and to three
      different techniques currently used in preventing it. Parental support for
      teaching preschool children personal safety skills was unanimous and the school
      based videotaped role-play program, which explicitly demonstrates personal safety
      skills, was the first choice of 57% of the parents.

PMID- 8302986
TI  - Effects of pretrial publicity on male and female jurors and judges in a mock rape
      trial.
AB  - A study explored influence of pretrial publicity and gender identity on verdicts
      and severity of sentence in a mock rape trial. Mock jurors and judges were
      exposed to four pretrial publicity conditions before watching a simulated rape
      trial. After viewing the trial, jurors rendered a verdict (guilty or not guilty)
      and judges prescribed a sentence. The Bem Sex-role Inventory was used to analyze
      gender identity and its relation to verdict and sentencing. Verdicts were not
      influenced by pretrial publicity, but sentencing was more severe following
      exposure of mock judges to pretrial publicity about a mistaken acquittal and less
      severe following exposure of these judges to pretrial publicity about a mistaken
      conviction. Subjects classified by the Bem inventory as feminine or androgynous
      rendered a verdict of "guilty" more often than subjects classified as masculine
      or undifferentiated. Men who rendered verdicts of "guilty" had less confidence in
      their judgments than men who found the defendant "not guilty." Conversely, women
      who found the defendant "not guilty" expressed less confidence than women who
      found the defendant "guilty." The findings are compared and contrasted with
      similar studies and discussed in regards to gender identity, subjects'
      characteristics, and mode of presentation.

PMID- 8302987
TI  - Management of death and grief in obituary and in memoriam pages of Nigerian
      newspapers.
AB  - This analysis of obituaries and in memoriam advertisements in Nigerian newspapers
      provides the identification of dimensions of content used to manage death and
      grief. Ten dimensions of content were abstracted: pictorial representation is a
      widespread practice, immediacy of announcement following death is an appropriate
      etiquette in the management of death, funeral arrangements are included as open
      invitation to a community of mourners, advertisements indicate direct contact and
      communication with the deceased, contents suggest the belief in personal
      immortality of the soul, religion is a pervasive and dominating force in
      advertisements, there are similarities in choice of words used in death
      advertisements, there is recognition of the temporal nature of life, mourning
      seems to be an ongoing process, and often the deceased is perceived as resting in
      peace. Never do obituaries and in memoriam statements include the flaws of the
      deceased. Clearly, the dimensions of content in the obituaries and in memoriam
      advertisements of Nigerian newspapers are a specific cultural behavior of people
      who exhibit similarity in the management of death and grief. These advertisements
      serve as an unbroken link between the deceased and the bereaved. This study also
      suggests that openness to death is the appropriate etiquette in the management of
      death and grief in Nigeria.

PMID- 8302988
TI  - Self-focus, other-focus, and interpersonal needs as correlates of loneliness.
AB  - Residential college students (44 men, 51 women) participated in a questionnaire
      study to clarify the relationship between loneliness, self- or other-focus, and
      interpersonal needs. Contrary to predictions, loneliness was unrelated to self
      focus, other-focus, or the ability to elicit disclosure from others. However, sex
      differences were found on interpersonal needs. Specifically, loneliness in men
      was predicted by a lack of expressed inclusion and a desire for control from
      others, while loneliness in women was predicted by a lack of expressed affection.
      These findings suggest that lonely men and women may benefit from different
      intervention strategies. Outcome studies are needed to ensure that such
      interventions actually reduce loneliness.

PMID- 8302989
TI  - WAIS--R scatter with psychiatric inpatients: II. Intersubtest scatter.
AB  - Intersubtest scatter values for the Full, Verbal, and Performance Scales of the
      WAIS--R were estimated for a sample of 163 psychiatric inpatients and compared
      with those reported for the WAIS--R standardization group using the normal
      deviate (z) test. Intersubtest scatter was assessed using the range and the
      Profile Variability Index. Results were surprising and conflicted with what was
      expected based on the clinical literature. First, in comparison to the
      standardization group, the psychiatric inpatients showed significantly more
      intersubtest scatter on the Verbal Scale only, while Performance Scale values
      were comparable. Second, the psychiatric inpatient sample, as a group, showed
      identical amounts of scatter on the Verbal and Performance Scales. Results
      suggest that the interpretation of intersubtest scatter as a sign of
      psychopathology should be avoided.

PMID- 8302990
TI  - Multidimensional perfectionism and academic procrastination: relationships with
      depression in university students.
AB  - Depression in university students is associated with numerous problematic
      outcomes. Unidimensional perfectionism and academic procrastination have each
      independently been related with depression and with one another in university
      students. Multidimensional perfectionism, consisting of self and social
      dimensions, and academic procrastination have not been simultaneously examined
      for their interrelationships with one another and with depression. Measures of
      multidimensional perfectionism, academic procrastination, and depression were
      administered to 150 undergraduate and graduate students. Analyses showed that
      only one dimension of perfectionism was correlated with procrastination, although
      both perfectionism and procrastination were important in accounting for
      depression in these students. Findings are discussed as they relate to the
      treatment of university students for the symptoms of depression.

PMID- 8302991
TI  - Neuropsychiatric update of the crime "profile" and "signature" in single or
      serial homicides: rule out limbic psychotic trigger reaction.
AB  - A neuropsychiatric and -psychological update of the crime "profile" and
      "signature" is a necessary addition to the traditional sociopsychological model
      likely to miss limbic system dysfunctioning. Thus, occurrence of a brief (c. 20
      minutes) limbic seizure has been proposed based on behaviors of 12 white male
      homicidal loners, who showed a dozen symptoms and signs: Limbic Psychotic Trigger
      Reaction. Readily overlooked can be (a) a transient psychosis (hallucinations
      and/or delusions), (b) autonomic hyperactivation (e.g., loss of bladder control,
      nausea, ejaculation), (c) motiveless, out-of-character, unplanned, and well
      remembered homicidal acts, (d) committed with a flat affect (not emotionally or
      impulsively provoked), (e) typically involving a stranger who happened to provide
      an objectively harmless and only subjectively important stimulus. (f) Such an
      individualized stimulus triggered the memory revival of mild to moderate but
      repeatedly experienced hurts. Such a specific sequence of events implicates the
      specific mechanism of limbic seizure, "kindling," which does not necessarily
      involve motor convulsions. Repetition of such limbic episodes with "criminal
      acts" is conceivable under specific circumstances including cases in which the
      triggering stimulus is associated with pleasurable delusions (e.g., of grandiose
      power or wealth) or constitutes a specific aspect of a basic drive motive. For
      example, eating or sexual activities might be planned but degenerate into a
      limbic episode with a specific core symptomatology.

PMID- 8302992
TI  - Clinical note on MMPI Posttraumatic Stress Disorder Scale (PK).
AB  - An MMPI scale for the detection of Posttraumatic Stress Disorder has been altered
      in MMPI-2. The entire scale, not readily retrievable, is presented for the MMPI
      group form.

PMID- 8302993
TI  - Diagnosis of disruptive behavior disorders using the Millon Adolescent
      Personality Inventory.
AB  - Millon Adolescent Personality Inventory differential diagnosis of disruptive
      behavior disorder vs no behavior disorder was investigated. Results were twice
      cross-validated. Millon adolescent Scales 4, 5, 6, G, SS, and TT were closely
      related to diagnosis of behavior disorder. Two psychometric rules averaged 70%
      hits and 35% false positives over three samples, Rule 1 of > 2 elevations
      (baserate score > 63) among Scales 6-G-SS-TT and Rule 2 of Scale 4 elevated with
      Scale 5 or with one of 6-G-SS-TT. An ancillary rule was highly specific to
      behavior disorder (90%). Two broad dimensions or factors appeared to be
      represented in the key scales; Scales 4 and 5 exemplified a histrionic
      narcissistic factor, while the 6-G-SS-TT combination typified behavioral conflict
      and instability.

PMID- 8302994
TI  - Effectiveness of career-development courses for nontraditional premedical
      students: improving professional identity.
AB  - The purposes of this study were to examine the effects of three career
      development courses on the professional identities of participating students as
      measured by My Vocational Situation and to investigate the effect of gender on
      students' responses to the scale. A total of 64 students enrolled in a special
      premedical program took the scale as a pretest and again as a posttest after the
      completion of three career-development courses. Analysis yielded significant
      differences between pre- and posttest scores for the three subscales of
      Vocational Identity, Occupational Information, and Barriers. No significant
      gender differences were observed at pre- or posttest. Implications for further
      research designed to evaluate the effectiveness of intervention strategies in
      career development are discussed.

PMID- 8302995
TI  - Psychology of computer use: XXIX. Measuring computer users' stress: the Computer
      Hassles Scale.
AB  - Measurement of computer users' stress was based on the Computer Hassles Scale. 65
      questionnaires were returned from 113 mailed to users of accounting information
      systems who worked for manufacturing companies. Correlations were calculated for
      the total sample and subsamples divided by gender. The analysis indicated that
      persons with college degrees experienced greater computer users' stress than
      those who were without. Those persons who reported more computer hassles
      experienced more somatic complaints which indicated that the computer hassles
      were stressful. There were no significant mean differences between women and men
      on computer hassles or somatic complaints. The correlations of computer hassles
      with somatic complaints differed by gender. Women's computer hassles were
      significantly correlated .61 with somatic complaints, but men's computer hassles
      were not significantly correlated (r = .18) with somatic complaints. The gender
      differences suggest that there is a complex relationship between stressors
      (computer hassles) and stress reactions (somatic complaints).

PMID- 8302996
TI  - Effects of UCS intensity and duration of exposure of nonreinforced CS on
      conditioned electrodermal responses: an experimental analysis of the incubation
      theory of anxiety.
AB  - Eysenck's incubation theory of fear or anxiety was examined in a human Pavlovian
      conditioning experiment with skin-conductance responses as the dependent
      variable. The conditioned stimuli (CSs) were fear-relevant slides (snakes and
      spiders) and the unconditioned stimuli (UCSs) were aversive tones. Different
      groups of subjects were presented two tone intensities during the acquisition
      phase and three durations of nonreinforced CS (extinction phase) in a delay
      differential conditioning paradigm. Resistance to extinction of conditioned skin
      conductance responses (conditioned fear responses) exhibited was largest for high
      intensity of tone and short presentations of the nonreinforced CS (CS+presented
      alone). The result tends to support Eysenck's incubation theory of anxiety.

PMID- 8302997
TI  - The body type/temperament mismatch and self-actualization.
AB  - The Catell and Metzner (1993) finding of higher self-actualization among people
      with body type/temperament mismatch is important and could be viewed as support
      for a link of creativity with deviance. Also, there is an error in one of their
      statements, which is corrected here.

PMID- 8302998
TI  - Prediction of cancer and coronary heart disease as a function of method of
      questionnaire administration.
AB  - We have tested the hypothesis in this study that different methods of
      administering a questionnaire produce differential approximations to truthful
      admission of undesirable personality traits and behaviours. Four different
      methods of administration produced different levels of trust and understanding,
      using the current prediction among healthy subjects of death by cancer or
      coronary heart disease 13 years later as the criterion. There were significant
      differences in the accuracy of the predictions, depending crucially on the method
      of administration of the questionnaires. Best predictions were achieved for
      subjects when both trust and understanding had been increased by interviewers'
      suitable participation; worst results were achieved for subjects when no special
      effort was made to increase either. Intermediate results were found for
      procedures which increased either trust or understanding. It is argued that the
      success or failure of studies investigating the influence of personality and
      stress on diseases like cancer and coronary heart disease may depend crucially on
      the adopted method of interrogation.

PMID- 8302999
TI  - Personal vs social motivations of undergraduates for using alcohol.
AB  - The personal vs social motivations for using alcohol were assessed for 109
      undergraduates attending a midwestern technical university. Analysis indicated
      that alcohol was consumed more for social than for personal reasons and that men
      used alcohol more than women for the social reasons of meeting new people and
      meeting members of the opposite sex and for the personal reason of feeling better
      about themselves. Use was also associated with being a member of a fraternity or
      sorority and the total number of campus organizations in which students were
      involved. These results suggest that alcohol education programs should take into
      account the motivations on a particular campus for alcohol use.

PMID- 8303000
TI  - Obesity as a characterological stigma: the issue of responsibility and judgments
      of task performance.
AB  - A study was conducted to investigate whether beliefs about the cause of a
      person's obesity would influence attributions made about that person's task
      performance. 168 high school girls were shown a videotape of an obese or normal
      weight confederate playing a game and performing either above or below average.
      Half of the subjects seeing the obese girl were led to believe that her obesity
      was due to a glandular disorder beyond her control. Subjects rated the obese
      target as more self-indulgent and less self-disciplined than the normal-weight
      target, except when her obesity was said to have resulted from a glandular
      disorder. However, subjects did not differentially attribute the confederate's
      task performance as a function of her weight or her perceived responsibility for
      it. Corroborating the results of earlier studies, no evidence was found that
      these high school girls subscribe to the stereotype of the "jolly" fat person.

PMID- 8303001
TI  - MMPI-2 schizophrenia spectrum profiles among schizotypal college students and
      college students who seek psychological treatment.
AB  - The MMPI-2 schizophrenia spectrum profiles of 25 college students with extreme
      scores on the Perceptual Aberration and Magical Ideation Scales were compared to
      those of 27 students who requested psychological treatment at a university
      psychology clinic. Moldin, Gottesman, and Erlenmeyer-Kimling's 1987
      classification strategy for schizophrenia spectrum disorders identified 66% of
      the students who did not seek psychological treatment and had high scores on the
      Perceptual Aberration and Magical Ideation Scales as having an 8-6, 8-9, or a 9-8
      MMPI-2 profile. Of the students who requested psychological treatment, 25%
      produced MMPI-2 schizophrenia spectrum profiles. Of these, 63% produced a 2-7-8
      code profile. Additional analyses showed that only some of the students who
      requested psychological treatment and produced a 2-7-8 MMPI-2 profile exhibited
      schizotypal features and that this group stayed in therapy longer than students
      without schizophrenia spectrum profiles. These results suggest that only a subset
      of the students with high scores on the Perceptual Aberration and Magical
      Ideation Scales produce schizophrenia spectrum MMPI-2 profiles and that these
      profiles are substantially different from those produced by students with high
      scores on the Revised Social Anhedonia Scale and from schizotypal college
      students who seek psychological treatment.

PMID- 8303002
TI  - Epidemiology in public health in the era of health care reform.

PMID- 8303003
TI  - A nurse-delivered intervention to reduce barriers to breast and cervical cancer
      screening in Chicago inner city clinics.
AB  - An 18-month intervention was implemented to increase breast and cervical cancer
      screening among poor African-American women in Chicago. Breast and cervical
      cancer screening programs were set up in two public clinics, one community-based
      and the other hospital-based. Nurse clinicians and public health workers were
      used in these programs to recruit women in the clinics and in targeted community
      institutions to receive free breast and cervical cancer screening. The following
      barriers were specifically addressed by the intervention: accessibility of
      screening, knowledge about breast and cervical cancers, access to followup
      screening examinations, and access to treatment. A computerized followup system
      was specifically designed to track patients. During the 18 months of the
      intervention, 10,829 visits were made by 7,654 low-income women. A total of 84
      cases of breast cancer and 9 cases of cervical cancer were detected. Awareness of
      the program, as measured by a survey after the completion of the intervention,
      increased in both clinics compared with baseline results. Knowledge about breast
      and cervical cancers also increased, as measured by scores on tests given before
      and after a class on breast and cervical cancers. Followup rates were 86 percent
      for women attending the programs. More than 90 percent of the women referred for
      evaluation of breast abnormalities kept an appointment. In summary, the
      intervention was successful in reducing barriers to breast and cervical cancer
      detection and in attracting a high-risk group of women.

PMID- 8303004
TI  - Survey of state health agencies' staff who practice the epidemiology of
      noninfectious diseases and conditions.
AB  - The primary causes of mortality in the United States are noninfectious diseases
      and conditions. Epidemiologic and intervention activities related to most of
      these diseases and conditions have increased in most State health agencies over
      the past decade. Because little was known of the practice of noninfectious
      disease epidemiology in State health agencies, a mail survey was undertaken in
      1991. Persons working in State health agencies who responded to the survey had a
      graduate degree in epidemiology, biostatistics, or related fields and actively
      participated in the epidemiology of noninfectious diseases or conditions.
      Respondents were from 48 States, predominantly male (56 percent) and white (92
      percent). On an average, respondents spent roughly half of their time actually
      doing epidemiology. The focus of noninfectious disease epidemiology has been
      categorized by risk factors (environment, occupation, nutrition, tobacco, and
      substance abuse), diseases (diabetes, cancer, and cardiovascular disease), and
      health conditions (injury, birth defects, and other reproductive conditions). The
      percentage of respondents who reported epidemiologic activity in any risk factor,
      disease, or condition varied from 55 percent for environmental epidemiology to 9
      percent in nutritional epidemiology. Respondents from 41 States reported activity
      in environmental epidemiology, those from 18 States reported activity in
      substance-abuse epidemiology, and those from 13 States reported activity in
      nutritional epidemiology. Although the practice of noninfectious disease
      epidemiology appears to be considered important in the majority of States, the
      extent of practice varies markedly. Those risk factors, diseases, and conditions
      that are most frequently associated with morbidity and mortality are the least
      addressed epidemiologically in State health agencies. In addition,when events
      such as environmental disasters occur, appropriate surveillance systems
      frequently are not in place to monitor the most important health outcomes. As a
      result, public health planning and intervention programs may not be driven by
      solid epidemiologic data.

PMID- 8303005
TI  - The EPIGRAM computer program for analyzing mortality and population data sets.
AB  - EPIGRAM is a computer program designed to improve access to State-level
      underlying cause mortality data. The program produces results for population,
      deaths, death rate, age-adjusted death rate, years of potential life lost (YPLL),
      YPLL rate, and confidence intervals. Results can be compared variously among age
      groups, counties, causes of death, races, regions, and years. The program's menu
      driven interface facilitates the selection or modification of analysis
      parameters. Current selections are retained so the user can modify one parameter
      at a time. Based on the parameters that the user selects, the program produces a
      series of tables, one for each instance of a particular parameter. Each output
      table has columns for male, female, and both sexes combined, and an indefinite
      number of user-defined rows for age groups, causes of death, counties, races,
      regions, or years. EPIGRAM has major advantages over other methods for analyzing
      mortality and population data. The program uses relatively small amounts of
      memory and disk space, executes rapidly, is flexible, can be used by
      inexperienced computer users, provides online help screens and tutorials, and
      runs under DOS or UNIX without modification. The program currently is used to
      analyze mortality and population data for Texas. Although it is not currently
      available for distribution, support is being sought for its evaluation and
      possible implementation in State health departments to analyze data for other
      States, or other data sets, such as hospital discharge data or cancer incidence
      data.

PMID- 8303006
TI  - Public attitudes about cigarette smoking: results from the 1990 Smoking Activity
      Volunteer Executed Survey.
AB  - The 1990 Smoking Activity Volunteer Executed Survey collected information on a
      wide range of policy-relevant issues concerning public attitudes about cigarette
      smoking. These issues include cigarette taxes, advertising restrictions, minors'
      access to tobacco products, school-based prevention, and exposure to
      environmental tobacco smoke in workplaces and public areas. Survey data were
      collected during the spring and summer months of 1990 from random samples of
      adults from Arizona, Michigan, Pennsylvania, and Texas. Telephone interviews were
      conducted by trained American Cancer Society volunteers using standardized
      questionnaires. Cluster sampling techniques, interviewer training and
      supervision, and data collection procedures were designed in conformity with the
      methodology of the Behavioral Risk Factor Surveillance System of the Centers for
      Disease Control and Prevention. Smoking prevalence ranged from a low of
      approximately 20 percent in Texas to a high of 31 percent in Michigan. Between 60
      and 69 percent of the respondents in the four States, including between 44 and 71
      percent of current smokers, believe tobacco should be classified as a drug.
      Around 65 percent of the respondents would support an extra tax on tobacco to
      finance public campaigns against smoking, and between 61 percent and 69 percent
      favor banning cigarette advertising in the print media and on billboards. More
      than 82 percent of the respondents believe that stronger laws should be enacted
      to prevent the sale of tobacco products to minors, and more than 86 percent
      believe that existing laws should be better enforced. Current smokers were only
      slightly less likely than were former and never smokers to indicate support of
      policy changes to prevent minors'access to tobacco products; the two groups had
      somewhat more disagreement in the amount of support for the other smoking control
      policies.Finally, although between 62 and 88 percent of working respondents
      reported the presence of smoking restrictions at their workplace, between 26 and
      48 percent still reported being bothered by smoking at work.These study findings
      suggest that existing smoking control policies are not restrictive enough or are
      inadequately enforced. The study documents strong public concern in the four
      States about the in adequacy of current policies and support for the enactment of
      stronger legislation to control smoking behavior.

PMID- 8303008
TI  - HRSA approves HIV-AIDS grants for adolescents, Native Americans.

PMID- 8303007
TI  - A community view of smoking cessation counseling in the practices of physicians
      and dentists.
AB  - The practice norms of community physicians and dentists in the Lehigh Valley of
      Pennsylvania for counseling about smoking cessation were surveyed. In addition,
      1,373 residents in the valley were interviewed by telephone about the smoking
      counseling behaviors of their dentists and physicians. These activities were
      conducted as part of the planning for an intervention by the Coalition for a
      Smoke-Free Valley, a coalition of 100 persons and organizations in the area. The
      survey response rate for 172 physicians was 77 percent, and for 103 dentists, it
      was 76 percent. More physicians than dentists advised patients to quit, counseled
      patients, provided materials, and helped the patient to set a quit date. However,
      there was a clear discrepancy between what physicians say they do and what
      smokers say they hear.

PMID- 8303009
TI  - WHO AIDS program director calls for revamping of medical education.

PMID- 8303010
TI  - Issues regarding data on race and ethnicity: the Census Bureau experience.
AB  - In this paper, the authors describe some of the complexities of collecting and
      presenting data on race and ethnicity based on the experiences of the Bureau of
      the Census. Different methods of data collection, different content and format of
      questions, and different definitions make it difficult to collect consistent race
      and ethnic data across data systems. The Bureau of the Census experiences have
      shown that changing ethnic self-identity and concepts, intent of the question,
      consistency of reporting, and the classification of persons of mixed racial
      parentage affect the quality of the data. These are some of the issues that must
      be addressed as statistical agencies and researchers seek to provide comparable
      race and ethnic data.

PMID- 8303012
TI  - The use of race and ethnicity in public health surveillance.

PMID- 8303011
TI  - The concept of race and health status in America.
AB  - Race is an unscientific, societally constructed taxonomy that is based on an
      ideology that views some human population groups as inherently superior to others
      on the basis of external physical characteristics or geographic origin. The
      concept of race is socially meaningful but of limited biological significance.
      Racial or ethnic variations in health status result primarily from variations
      among races in exposure or vulnerability to behavioral, psychosocial, material,
      and environmental risk factors and resources. Additional data that capture the
      specific factors that contribute to group differences in disease must be
      collected. However, reductions in racial disparities in health will ultimately
      require change in the larger societal institutions and structures that determine
      exposure to pathogenic conditions. More attention needs to be given to the ways
      that racism, in its multiple forms, affects health status. Socio-economic status
      is a central determinant of health status, overlaps the concept of race, but is
      not equivalent to race. Inadequate attention has been given to the range of
      variation in social, cultural, and health characteristics within and between
      racial or ethnic minority populations. There is a growing emphasis, both within
      and without the Federal Government, on the collection of racial or ethnic
      identifiers in health data systems, but noncoverage of the Asian and Pacific
      Islander population, Native Americans, and subgroups of the Hispanic population
      is still a major problem. However, for all racial or ethnic groups, we need not
      only more data but better data. We must be more active in directly measuring the
      health-related aspects of belonging to these social categories.

PMID- 8303013
TI  - A private sector view of health, surveillance, and communities of color.
AB  - The U.S. population is fast evolving into a patchwork of health behaviors,
      incomes, and ethnic backgrounds. Simple cultural labeling will not do. A growing
      number of Americans, now numbering about 10 million, cannot or will not describe
      their race in any one of the Census Bureau's standard categories--white, black,
      American Indian, Eskimo, Aleut, Asian Pacific, or Hispanic. They group themselves
      as a multicultural population rather than a single racial or ethnic category. To
      guide health interventions, the private sector now relies more on statistical
      clusters based on geography, lifestyle, behavior, financial status, and attitudes
      instead of on race. In marketing, the challenge is to reach diverse markets
      without stereotyping the product as one designed for only a certain ethnic group.
      The emphasis on athletics instead of on race is one example of how some marketers
      solve this problem of reaching minorities without giving the impression that
      specific products are only for blacks, or Hispanics, or Asians. Surveillance
      professionals can expand the way data are collected and publicized. Blacks,
      Hispanics, Asians, and Native Americans should not be categorized simply by race;
      other variables of health, such as income and age, should be given careful
      attention.

PMID- 8303014
TI  - A case study in the use of race and ethnicity in public health surveillance.
AB  - Increased attention has been focused on the use of racial and ethnic categories
      in public health research and surveillance in recent years. This attention,
      however, has done more to increase the collective awareness of the difficulties
      inherent in these classification schemes than to resolve either the theoretical
      or practical problems. It has been recognized for many years that health outcomes
      for a particular ethnic population must be seen as an interaction between
      genetically determined factors and socially mediated exposures. The operational
      meaning of these concepts remains poorly defined, however. Although the general
      biologic construct of race and ethnicity appears straightforward, appearance is
      deceiving and the technical requirements that allow formulation of a rigorous and
      objective working definition have never been fully developed. The social factors
      that influence ethnic health differentials are perhaps better understood in
      practical terms; measurement of many of the relevant variables remains difficult,
      however. In this article an attempt is made to outline the implications of the
      new developments in molecular biology for the concept of race, and to provide an
      illustrative example of the continued evolution of the social determinants of
      ethnicity.

PMID- 8303015
TI  - Guidelines for designing rapid assessment surveys of HIV seroprevalence among
      hospitalized patients. Centers for Disease Control and Prevention.
AB  - The Centers for Disease Control and Prevention has developed guidelines for
      determining HIV seroprevalence among patients seeking medical care at acute-care
      hospitals. The guidelines enable hospital staff members to perform a simple,
      rapid, and inexpensive survey to determine seroprevalence among the patient
      population, protecting the anonymity of those who are tested. The guidelines are
      based on national experience with large-scale anonymous, unlinked HIV
      serosurveys. The data from a rapid assessment survey are particularly useful for
      evaluating the need to provide routine, voluntary HIV counseling and testing and
      treatment for HIV infection. Beyond that, such data can be used in targeting
      education efforts, in reinforcing the use of appropriate universal precautions,
      in resource allocation, and in determining the need for further studies of HIV
      infection among the population in the hospital catchment area.

PMID- 8303016
TI  - Foster care of HIV-positive children in the United States.
AB  - A national study regarding the foster care of children identified as human
      immunodeficiency virus-positive (HIV-positive) was conducted in 1991. A survey
      form was sent to the administrators of the State agency responsible for foster
      care in each State, the District of Columbia, and U.S. Territories for a total
      sample size of 55. After followup, all 55 responded for a response rate of 100
      percent. The number of children in foster care was ascertained for the current
      year and cumulatively. In 1991, 1,149 HIV-positive children were reported to be
      in foster care. Most States (49) had a general foster care policy and 21 had
      specific policies regarding care of a foster child who is HIV-positive. Measures
      and criteria used for recruitment were examined. In regard to recruitment
      policies, only seven States mandated recruitment of families specifically for
      children with HIV and acquired immunodeficiency syndrome. The major topics
      covered in training for HIV foster families included confidentiality, behavioral
      management, working with natural families, emotional factors, separation and
      loss, and others. Other issues discussed are foster parent training, supplemental
      services, later adoption possibilities, payments, and the expressed fears and
      doubts of foster parents caring for HIV-positive children. It is recommended that
      a national conference address the issues.

PMID- 8303017
TI  - Prenatal care needs assessment comparing service use and outcomes in Fresno, CA.
AB  - The authors performed a prenatal care needs assessment for Fresno County, CA,
      using data from a sample of 11,878 birth certificates for the county for 1989.
      Birth records, patterns of prenatal care utilization, and low birth weight
      outcomes in the county were compared with those in a random sample of 11,826
      certificates derived from births in the remainder of the State. Bivariate
      techniques were used in calculating care utilization rates. Multivariate logistic
      regression analysis was used in associating rates of prenatal care visits and
      gestational month of initiation of prenatal care with low weight birth outcomes.
      County women entered prenatal care as early as women in the remainder of the
      State, but did not return as often for prenatal care visits. Their rate of return
      for followup visits was 29.9 percent, compared with 24.8 percent for women in all
      other counties (P < 0.001). County women with the lowest rates of visits had 1.4
      to 1.9 times the risk of having a low weight birth than other county women with
      higher rates of visits, and a significantly higher risk than for women of all
      other counties. An intensive visit schedule for high-risk care was provided 28.9
      percent of county women, compared with 33.0 percent of women in all other
      counties (P < 0.001). County women who received a high-risk intensive visit
      schedule were 2.5 times more likely to have a low weight birth than county women
      who did not receive the schedule. For all other women in the State, the
      comparable risk was 2.1 times. Improvements in the number and content of prenatal
      care visits were shown to have a high likelihood of substantially improving birth
      weight outcomes for pregnancies among Fresno County women.

PMID- 8303018
TI  - Race and ethnicity in public health surveillance: criteria for the scientific use
      of social categories.
AB  - Public health surveillance is the cornerstone of public health practice. The uses
      of surveillance include the identification of patterns of health among population
      subgroups. The assessment of race and ethnicity in public health surveillance is
      fundamental to the reduction of preventable excesses in poor health among racial
      and ethnic populations. We review the use of race and ethnic variables in
      national public health surveillance systems in the United States. One barrier to
      the use of race and ethnicity in public health surveillance is the lack of
      scientific consensus on the nature of race and ethnicity and the measurement of
      these variables. Differences in terminology, data collection procedures,
      perceptions of group identity, and changing demographics of the U.S. population
      present particular challenges for surveillance. We propose criteria for any
      useful variables collected through surveillance. Application of these criteria to
      race and ethnicity suggests that race as assessed in surveillance is not
      primarily associated with biological characteristics, but it is more like
      ethnicity--a matter of self-perceived membership in population groups. Regular
      evaluation of surveillance systems will contribute to the usefulness of
      information on race and ethnicity in the improvement of the health of minority
      populations.

PMID- 8303019
TI  - Increasing the pool of qualified minority medical school applicants: premedical
      training at historically black colleges and universities.
AB  - Historically black colleges and universities have educated significant numbers of
      black students preparing for careers in medicine. These institutions have the
      potential to make even greater contributions to the pool of black medical school
      applicants and ultimately to the supply of black physicians. The Division of
      Disadvantaged Assistance, Bureau of Health Professions, Health Resources and
      Services Administration within the Public Health Service, commissioned a study of
      the curriculums and other factors related to premedical education. The study was
      conducted at the historically black colleges and universities that graduate a
      large number of students who gain admission to medical school, and the
      historically black colleges and universities whose students are less successful
      in gaining admission to medical school. Nine historically black colleges and
      universities participated in a self-assessment of their undergraduate premedical
      curriculums. The findings from schools with higher acceptance rates were compared
      with those of schools with lower acceptance rates to identify factors
      contributing to the production of significant numbers of successful medical
      school applicants. Comparisons of data on these schools revealed several
      important factors that may be related to differences in acceptance rates: Those
      schools that devoted greater effort to premedical training (for example, advising
      students about how to prepare for medical school, curriculum development,
      maintaining premedical or pre-health professions offices and clubs--the staff of
      these offices provide students with information on medical or other health
      professions schools--to identify and recruit students) tended to have higher
      acceptance rates. * Schools with higher acceptance rates had larger proportions
      of biology and chemistry majors aspiring to medical and dental careers and
      stronger affiliations with medical schools than schools with lower acceptance
      rates.* Institutions with higher acceptance rates offered a broader range of
      externally sponsored enrichment programs; the highest medical school acceptance
      rates were found among those schools with continuing Health Careers Opportunity
      Program projects that served significant percentages of students interested in
      careers in medicine.* Mean Medical College Admission Test scores were somewhat
      lower for applicants from schools with lower acceptance rates, but the great
      variation in acceptance rates for these schools is not reflected in a comparable
      variation in the Medical College Admission Test scores.

PMID- 8303020
TI  - Materials and strategies that work in low literacy health communication.
AB  - In a Maine Area Health Education Center program some solutions were developed to
      the well-documented problem of health information material that cannot be read or
      comprehended by low literacy adults. Professionals in health education and adult
      education were trained to produce easy-to-read health materials and created
      dozens of low-cost pamphlets on the nation's year 2000 health objectives. The
      pamphlets are easily reproducible on a copy machine. Concurrently, a model for
      teaching oral communication skills to health care providers who deal with low
      literacy adults was developed in partnership with Maine's largest rural health
      center delivery system. The train-the-trainers model reached more than 500 direct
      health care service providers. Participants in the two programs gained skills
      useful in all aspects of public communication that are replicable in other
      cities, States, and regions.

PMID- 8303023
TI  - [Diagnostic imaging of abdominal tumors in children].
AB  - Further technological progress in cross-sectional imaging modalities,
      accumulating experience with increasingly refined hardware and software and
      accumulating specific contrast media allow new algorithms for the assessment of
      abdominal tumors in children. However, ultrasound remains the diagnostic method
      of choice: conventional roentgenology with or without contrast media is
      decreasing, but often reveals further differential diagnostic details. MRI is
      becoming more prominent and is often performed immediately after ultrasound. The
      inauguration of gradient echo sequences and consequent shorter examination times
      combined with the elimination of pulsation and motion artefacts extends the
      diagnostic spectrum of the upper and middle abdomen. The application of oral or
      rectal contrast agents for imaging of the GI tract ameliorates the
      differentiation of pathologic processes. Recently volumetric CT/ultrafast CT has
      been gaining in importance for abdominal examinations in the pediatric age group.
      CT especially is helpful if there are bony structures in the region being
      examined. CT, however, involves ionizing radiation and timely administration of
      oral and intravenous contrast material. Moreover, as pediatric radiologists, we
      must strongly withstand tendencies to perform CT more often because it is less
      expensive, rather than avoiding ionizing radiation by using MRI.

PMID- 8303021
TI  - Cholesterol screening in a community health promotion program: epidemiologic
      results from a biracial population.
AB  - The prevalence and interrelationship of high blood cholesterol levels with other
      cardiovascular disease risk factors were studied in a biracial suburb of New York
      City. Participants in community-based screenings to determine blood cholesterol
      levels have been predominantly white women in older age groups, highly educated
      and nonsmokers. To reach a more representative segment of a local population and
      promote healthy lifestyle behaviors, cholesterol screenings were conducted within
      an ongoing health promotion program in Mount Vernon, NY. Plasma cholesterol
      levels were determined for 5,011 participants, including 2,308 whites and 1,778
      blacks. Of the men, 29 percent had high cholesterol levels; among women, it was
      27 percent. Of the men with high levels, half had levels greater than 200
      milligrams per deciliter, as did 55 percent of the women. After statistical
      adjustments were made for age and other risk factors for high blood cholesterol,
      mean cholesterol levels were higher for whites than blacks. The level for white
      men was 204 milligrams per deciliter; for women, 212. For black men, the level
      was 199 milligrams per deciliter; for women, 208, P < .10. Hispanic men had
      levels of 199, P < .10. The levels for Hispanic women (203 milligrams per
      deciliter) were significantly lower than that of white women. Among whites who
      smoked more than 1 pack of cigarettes per day, mean cholesterol levels were 11
      milligrams per deciliter higher than for those who never smoked or were light
      smokers (0, 1-20 cigarettes per day, P < .10). There were too few who smoked more
      than 1 pack to test this association adequately among blacks. The mean
      cholesterol levels for hypertensive black men were 10 milligrams per deciliter
      greater than for black men with normal blood pressure (P<.10).

PMID- 8303022
TI  - Mammography and Pap smear screening of Yaqui Indian women.
AB  - The Pascua-Yaqui Tribe of Arizona receives its health care services at a local
      neighborhood health center in Tucson and a satellite clinic located on the
      reservation. Using a computerized data base from the health center, the authors
      determined the use rates by Pascua-Yaqui women ages 35-65 of the Papanicolaou
      smear and mammography screening. Among active users of the health center, 31-36
      percent had received a Papanicolaou smear, according to the yearly data bases
      examined from 1986 to 1990, while 65 percent of the women had received at least
      one smear test over the entire 5-year period. Regarding mammography screening, 41
      43 percent of the women ages 50-65 had received a mammogram in the years studied,
      and 51-58 percent of the women ages 40-49 had been screened. In all, 67 percent
      had received at least one mammogram during the 1988-90 period when the center
      offered mammography. This population of 35-65-year-old American Indian women, for
      whom financial access is not a barrier, were receiving Papanicolaou smears and
      mammograms at rates comparable with other segments of the U.S. population but at
      lower rates than those recommended by the American Cancer Society and National
      Cancer Institute. The challenge for the health center is to reach those women who
      are eligible for services but do not use them and to address the nonfinancial
      barriers to care such as language, transportation, and gender-specific issues.

PMID- 8303024
TI  - [Integrative imaging of nephroblastomas and nephroblastomatosis].
AB  - Studies on Wilms' tumor have led to intensive investigation of the relationship
      between nephroblastosis and nephroblastomatosis. Diagnostic strategies have
      changed: excretory urography is no longer recommended since all information
      needed is readily obtained by other imaging modalities. Ultrasound is used for
      the initial examination and confirms the presence and the localization of the
      mass. CT scan reveals perirenal invasion, and MRI allows the determination of
      tumor volume and confirmation or exclusion of vascular involvement.

PMID- 8303025
TI  - [The abdominal neuroblastoma].
AB  - Diagnosis of abdominal neuroblastoma by imaging techniques is demanding, and in
      most cases several complementary modalities are needed for correct staging.
      Ultrasonography is performed first, followed by contrast CT and/or MRI. Both
      skeletal and specific MIBG scintigraphy are essential in most cases. This applies
      not only for the primary diagnosis but also for monitoring the response to
      therapy and for picking up recurrent disease.

PMID- 8303026
TI  - [Liver tumors in children].
AB  - In the evaluation of a hepatic mass lesion, imaging techniques are of
      considerable importance, though the final diagnosis is established by
      histopathological examination. Radical surgery is still the best treatment for a
      primary malignant hepatic neoplasm and the surgeon should supplied in advance
      with all the information needed for planning the operation. Sonography is now the
      first diagnostic procedure performed, quite often followed by MRI as the only
      supplementary modality. Scintigraphy and angiography have been largely
      superseded; they are performed in carefully selected individual cases. CT is an
      alternative to MRI.

PMID- 8303027
TI  - [The use of imaging procedures in gastrointestinal diseases with space-occupying
      lesions in children].
AB  - Sonography is gaining in importance for examination of childhood illnesses of the
      gastrointestinal tract. Disadvantages of ultrasound result from the gaseous
      elements naturally contained in the intestine. Tumors of the digestive tract can
      be best classified on the basis of their relationship to the tract wall and their
      intra- or extraluminal location. The type of echogenicity can also aid diagnosis.
      A differentiation between infectious pseudotumors and neoplasms is thus often
      possible when sonographic images are considered in combination with clinical and
      laboratory data. The systematic use of ultrasound also allows more precise
      application of endoscopy and other imaging techniques.

PMID- 8303028
TI  - [Vascular imaging with spiral-CT. The path to CT-angiography].
AB  - Spiral CT is a technique that allows for high-quality two-dimensional
      angiographic projections and 3D imaging of vascular structures. The authors
      present the technical and methodological principles of the technique, including
      scan parameters and parameters of contrast application for various clinical
      imaging tasks. They present their experience with over 150 clinical cases using
      spiral CT angiography. Suitable applications of this technique include congenital
      anomalies, aneurysms, dissections, stenoses, thrombi and vascular tumor
      involvement. Given a problem-adapted examination technique, pathologic changes in
      vessels of as little as 2 mm can be visualized. In some cases with complex
      vascular anatomy, spiral CT angiography can be superior to arterial angiography.

PMID- 8303029
TI  - [An unclear deglutition disorder].

PMID- 8303030
TI  - "Reasonable accommodations" for disabled nurses.

PMID- 8303031
TI  - Supreme Court lays down law in sexual harassment cases. Case in point: Harris v.
      Forklife Systems, Inc. 114A Ct. 2d 367--TN (1992).

PMID- 8303032
TI  - Legal case briefs for nurses. PA: combative patient strikes nurse's aide:
      "specific loss" of sight comp. claim; LA: nurse allegedly bumps patient with
      door: no documentation by Dr., nurse or hospital.

PMID- 8303033
TI  - "Implementing doctor's orders" is no defense. Case in point: Bremner v. Charles
      859 P. 2d 1148--OR (1993).

PMID- 8303034
TI  - Recent advances in the chemistry and biology of retinoids.

PMID- 8303035
TI  - Approach to the chemotopography of the digitalis recognition matrix in Na+/K(+)
      transporting ATPase as a step in the rational design of new inotropic steroids.

PMID- 8303036
TI  - Inhibitors of enkephalin-degrading enzymes as potential therapeutic agents.
AB  - A limited number of enzymes such as membrane metalloendopeptidase (enkephalinase)
      and angiotensin converting enzyme appear to be involved in deactivation and
      modulation of circulatory regulatory peptides. Peptides such as the enkephalins
      are also involved in a large number of physiological processes. This multiplicity
      of physiological roles has made it difficult to establish the therapeutic role of
      enkephalin-degrading enzyme inhibitors. Other factors such as difficulty in
      quantification and thus measurement of processes involved in pain and mental
      illness have also hindered the process of establishing any therapeutic role of
      enkephalin-degrading enzyme inhibitors in these conditions. However, they have
      proved to be useful pharmacological 'tools'. The most likely therapeutic role at
      present appears to be in the treatment of cardiovascular disorders. As a
      'profile' of pharmacological actions of enkephalin-degrading enzymes emerges, it
      is becoming apparent that bioavailability rather than a high degree of
      specificity or inhibitory potency may be the most important factor. This may be
      used to an advantage in future developments by the use of less specific or
      combined inhibitors in the form of prodrugs, designed to be active at specific
      sites such as the central nervous system.

PMID- 8303037
TI  - Semi-synthetic derivatives of erythromycin.
AB  - Semi-synthetic derivatives of erythromycin have played an important role in
      antimicrobial chemotherapy. First generation derivatives such as 2'-esters and
      acid-addition salts significantly improved the chemical stability and oral
      bioavailability of erythromycin. A second generation of erythronolide-modified
      derivatives: roxithromycin, clarithromycin, azithromycin, dirithromycin and
      flurithromycin, have been synthesized and have exhibited significant improvements
      in pharmacokinetic and/or microbiological features. In addition, erythromycin
      itself has expanded its utility as an effective antibiotic against a variety of
      newly emerged pathogens. As a result of these developments, macrolide antibiotics
      have enjoyed a resurgence in clinical interest and use during the past half-dozen
      years, and semi-synthetic derivatives of erythromycin should continue to be
      important contributors to this macrolide renaissance. Despite these recent
      successes, other useful niches for macrolide antibiotics will remain unfilled.
      Consequently, the search for new semi-synthetic derivatives of erythromycin
      possessing even better antimicrobial properties should be pursued.

PMID- 8303038
TI  - [Trends in the study on microtubules].

PMID- 8303039
TI  - [Targets and background of nanobiology: a biology with highest resolution].

PMID- 8303040
TI  - [Analytical ultracentrifugation: why now?].

PMID- 8303041
TI  - [The new future of analytical ultracentrifugation].

PMID- 8303042
TI  - [Regulation of Src family tyrosine-kinases by Csk].

PMID- 8303043
TI  - [Recent progress in enzymology and molecular biology of enzymes involved in
      calcium homeostasis].

PMID- 8303044
TI  - Evoking the permission schema: the impact of explicit negation and a violation
      checking context.
AB  - Cheng and Holyoak (1985) proposed that realistic reasoning in deontic contexts is
      based on pragmatic schemas such as those for assessing compliance with or
      violation of permission and obligation rules, and that the evocation of these
      schemas can facilitate performance in Wason's (1966) selection task. The
      inferential rules in such schemas are intermediate in generality between the
      content-independent rules proposed by logicians and specific cases stored in
      memory. In one test of their theory, Cheng and Holyoak demonstrated that
      facilitation could be obtained even for an abstract permission rule that is
      devoid of concrete thematic content. Jackson and Griggs (1990) argued on the
      basis of several experiments that such facilitation is not due to evocation of a
      permission schema, but, rather, results from a combination of presentation
      factors: the presence of explicit negatives in the statement of cases and the
      presence of a violation-checking context. Their conclusion calls into question
      both the generality of content effects in reasoning and the explanation of these
      effects. We note that Jackson and Griggs did not test whether the same
      combination of presentation factors would produce facilitation for an arbitrary
      rule that does not involve deontic concepts, as their proposal would predict. The
      present study tested this prediction. Moreover, we extended Jackson and Griggs'
      comparisons between performance with an abstract permission rule versus an
      arbitrary rule, introducing clarifications in the statement of each. No
      facilitation was observed for an arbitrary rule even when explicit negatives and
      a violation-checking context were used, whereas strong facilitation was found for
      the abstract permission rule under the same conditions. Performance on the
      arbitrary rule was not improved even when the instructions indicated that the
      rule was conditional rather than biconditional. In contrast, a small but reliable
      degree of facilitation was obtained for the abstract permission rule, with
      violation-checking content even in the absence of explicit negatives. The theory
      of pragmatic reasoning schemas can account for both the present findings and
      those reported by Jackson and Griggs.

PMID- 8303045
TI  - Balantidium coli (Vestibuliferida: Balantidiidae): the persistence of an old
      problem.

PMID- 8303046
TI  - [Pathogenicity of equine influenza viruses in chickens].
AB  - In the present paper the pathogenicity of equine subtype A/equi 1 (H7N7) and
      A/equi 2 (H3N8) for chicks was studied. Strains previously isolated in Brazil,
      representatives of both subtypes, were used. Eight experiments were performed for
      A/equi 2, using 89 chicks (4 to 18-day old). Six hundred thirty three samples of
      cloacal material were collected from 01 to 15 days pos-infection (p.i.) and
      inoculated in 11-day old chick embryos for recuperation of virus. Twelve samples
      showed positive results. The recuperated viruses were identified with specific
      antiserum in hemagglutination inhibition test (HI). Blood samples of all chicks
      collected prior to infection showed no antibodies to both subtypes. Chicks
      inoculated with A/equi 2 virus were bled 18 to 21 days p.i. Out of 89, seventy
      one (79.8%) serums showed different levels of antibodies at HI tests. Seventy
      chicks were inoculated with A/equi 1 subtype. Five hundred forty three samples of
      cloacal material were harvested and inoculated in embryonated chick eggs. No
      recuperation of virus occurred. However, all the inoculated chickens showed
      seroconversion. Chicks infected with A/equi 2 may shed virus in feces. No signs
      of disease were noted in the inoculated chicks.

PMID- 8303047
TI  - [Coronary angioplasty and coronary surgery: the socioeconomic considerations].

PMID- 8303048
TI  - [Coronary angioplasty: the old and new indications].

PMID- 8303049
TI  - [Balloon angioplasty in the nineties: the lessons of a decade and the future
      prospects].

PMID- 8303050
TI  - [The angiographic assessment of the stenosis in coronary angioplasty: the
      usefulness of quantitative analysis systems].

PMID- 8303051
TI  - [Nonangiographic technics for assessing coronary stenosis. Intravascular
      echography and intracoronary Doppler].

PMID- 8303052
TI  - [Directional coronary atherectomy: the implications of a different modality of
      percutaneous revascularization].

PMID- 8303053
TI  - [The immediate and long-term utility of rotational atherotomes: extraction
      atherectomy and rotational ablation atherectomy].

PMID- 8303054
TI  - [Coronary angioplasty: balloon laser catheters and autoperfusion].

PMID- 8303055
TI  - [Thermal coronary angioplasty via radiofrequency catheter].

PMID- 8303056
TI  - [Percutaneous coronary angioscopy].

PMID- 8303057
TI  - [Coronary restenosis. An unresolved problem of percutaneous transluminal coronary
      angioplasty].

PMID- 8303058
TI  - [The treatment of acute coronary occlusion and of the post-coronary angioplasty
      "threat of occlusion" by the implant of an intracoronary prosthesis or stent].

PMID- 8303059
TI  - Effects of thymus humoral factor gamma-2 (THF gamma 2) on lymphohaematopoietic
      progenitor cells: an in vitro study.
AB  - Thymus humoral factor gamma-2 (THF gamma 2), an immunomodulatory factor, was
      previously shown to exert a regulatory effect upon human haematopoietic
      development. In the present study, we were primarily interested in determining
      whether THF gamma 2 has an immunorestorative effect after HIV infection. Although
      no inhibition of viral production by T-cluster-forming cells and their mature
      progeny was observed, this thymus-derived compound prevented the dramatic
      decrease in CD4+ cells observed in cultures of immature T cells from normal bone
      marrow infected with HIV 1.

PMID- 8303060
TI  - Squirrel monkey (Saimiri sciureus) B lymphocytes: secretion of IgG directed to
      Plasmodium falciparum antigens, by primed blood B lymphocytes restimulated in
      vitro with parasitized red blood cells.
AB  - Blood B lymphocytes obtained from Plasmodium falciparum-immune Saimiri monkeys
      were assayed for their in vitro differentiation in immunoglobulin-secreting cells
      upon restimulation with P. falciparum-parasitized Saimiri red blood cells.
      Selected culture conditions enabled appropriately stimulated blood B cells to
      secrete 3F11/G10+ IgG, detected in the supernatants by means of a dot
      immunobinding assay. Primed blood B lymphocytes from P. falciparum-immune Saimiri
      monkeys were thus able to secrete IgG when restimulated by parasitized red blood
      cells in the presence of T cell- and monocyte-derived cytokines (recombinant
      human cytokines). These primed blood B cells, which were able to differentiate,
      were shown to secrete antibodies reactive with P. falciparum-infected red blood
      cells, as detected by means of an indirect immunofluorescence assay, and reactive
      with P. falciparum-infected red blood cell extracts, as detected by means of
      Western blot analysis. Furthermore, due to the possibility of discriminating
      between IgG subtypes in the squirrel monkey (3F11/G10+::3A2/G6+ IgG [associated
      with protection against the blood stages of P. falciparum] vs. 3F11/G10+::3E4/H8+
      IgG [usually not functionally associated with protection]), we have attempted to
      estimate the respective proportions of each IgG subtype. In defined culture
      conditions, Saimiri monkey blood B cells preferentially secrete
      3F11/G10+::3E4/H8+ IgG in response to parasitized red blood cells. We therefore
      discuss the conditions that would render this assay suitable for the selection,
      among P. falciparum blood stage antigens, of those that have major B-cell
      epitopes.

PMID- 8303061
TI  - A theory of the ontogeny of the chicken humoral immune system: the consequences
      of diversification by gene hyperconversion and its extension to rabbit.
AB  - The immune system's repertoire is generated in two stages: Stage I results in a
      small size high copy number repertoire that is diversified by "mutation" to
      result in a large size low copy number repertoire referred to as Stage II. The
      Stage I or high copy number repertoire is derived from information stored
      directly in the genome by two mechanisms. (a) The copy-cassette mechanism: the Ig
      locus has one rearrangeable V gene segment which acts as recipient for controlled
      gene conversion in cis from a set of donor V gene segments that results in a
      family of subunits, L and H. This is illustrated by the avian systems. (b) The
      cassette-exchange mechanism: the Ig-locus has many rearrangeable V gene segments
      which are fused into transcription units, the products of which are a family of L
      and H subunits identical in function to those resulting from the copy-cassette
      mechanism. This is illustrated by the murine or human systems. It is possible for
      a species to use both mechanisms, copy-cassette at one Ig locus and cassette
      exchange at the other Ig locus. This seems to obtain in the rabbit system.
      Further, it is possible to encode the high copy number repertoire directly in the
      genome as tandemly repeated rearranged transcription units as one sees in shark
      (a genomic analogue of the cassette-exchange mechanism). We have discussed here
      and elsewhere (Cohn and Langman, 1990) the consequences of these mechanisms for
      haplotype exclusion and functional responsiveness to antigen. The Stage I or high
      copy number repertoire generated by any of the above mechanisms is now a
      substrate for "mutation" which generates the low copy number or Stage II
      repertoire. These three species are compared in table V. The high copy number
      repertoire is small but the response to any antigen that it recognizes is rapid.
      The low copy number repertoire is large but responsiveness to any antigen it
      recognizes is slow. Cooperativity between the two repertoires optimizes the
      overall responsiveness with respect to rapidity of response and range of
      responsiveness. The use of a copy-cassette mechanism requires that the phi B cell
      undergoing gene conversion have a single rearranged L- and H-chain haplotype
      (L+/oH+/o). The reason is that conversion can correct an aberrantly rearranged
      transcription unit and generate an unacceptable level of doubles. In order to
      have one chromosome functionally rearranged and the homologue in the germline
      configuration, a selection mechanism is required.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8303062
TI  - A bursal secretory dendritic cell and its contributions to the microenvironment
      of the developing bursal follicle.

PMID- 8303063
TI  - What is the function of germline-encoded VLVH specificity?

PMID- 8303064
TI  - Ligation of cell surface immunoglobulin in the chicken bursa of Fabricius.

PMID- 8303065
TI  - Five questions on the ontogeny of the chicken humoral immune system.

PMID- 8303066
TI  - Preimmune diversification creates a repertoire while somatic hypermutation fine
      tunes affinity--implications for the processes of mutation.

PMID- 8303067
TI  - A few comments about the Cohn and Langman theory of the ontogeny of the chicken
      humoral immune system.

PMID- 8303068
TI  - Special features of the development of the chicken humoral immune system.

PMID- 8303069
TI  - Rabbit facts and diversification of VH sequences by gene conversion: comments on
      "A theory of the ontogeny of the chicken humoral immune system: the consequences
      of diversification by gene hyperconversion and its extension to rabbit".

PMID- 8303070
TI  - An expanded view of the ontogeny of the rabbit humoral immune system.

PMID- 8303071
TI  - What in the dickens is with these chickens? An only slightly silly response to
      the first draft of Langman and Cohn.

PMID- 8303072
TI  - The role of the FDC-retained immune complex network and its dynamics in the
      activity of germinal centres.

PMID- 8303074
TI  - The structure of the IL4 gene and regulation of its expression.

PMID- 8303073
TI  - Trypanosoma cruzi glutathione-binding proteins (TcGBP): protection induced by
      native proteins in an experimental model and analysis of the antibody response.
AB  - Three Trypanosoma cruzi glutathione-binding proteins (TcGBP) of 45, 30 and 25 kDa
      presenting glutathione S transferase activity were characterized from T. cruzi
      epimastigotes. We show here that immunization of mice using TcGBP and complete
      Freund's adjuvant (CFA) did not protect the animals against a challenge with
      bloodstream trypomastigotes. In contrast, immunization of mice using TcGBP in
      association with Bordetella pertussis plus alum (BpAI) resulted in greatly
      diminished parasitaemia and significantly protected the animals from lethal
      infection. Using TcGBP mixed with BpAI and a lower challenge dose, we obtained
      strongly diminished parasitaemia and 100% protection in terms of survival. Only
      sera from mice immunized with TcGBP plus BpAI were able to kill trypomastigotes
      by complement-mediated lysis, whereas sera from mice immunized with TcGBP plus
      CFA did not. Interestingly, sera from mice immunized with TcGBP plus BpAI showed
      significant levels of specific IgE, IgG2a and IgG2b antibodies, whereas these
      isotypes were not detected in sera from mice immunized with TcGBP in CFA. All
      these levels were increased in sera of protected animals. These results
      demonstrate that TcGBP antigens can confer resistance to T. cruzi acute infection
      in mice, and suggest a possible functional role for both IgE and IgG2 isotypes in
      the induction of protective immunity.

PMID- 8303075
TI  - Current understanding of IL4 gene regulation in T cells.

PMID- 8303076
TI  - Interleukin 4 targeting of immunoglobulin heavy chain class-switch recombination.

PMID- 8303077
TI  - Structure of the IL4 receptor and signal transduction mechanism of IL4.

PMID- 8303078
TI  - Characterization of the interleukin 4 receptor. Structure and signal transduction
      pathways.

PMID- 8303079
TI  - Production of IL4 by human T cells and regulation of differentiation of T-cell
      subsets by IL4.

PMID- 8303080
TI  - Regulatory role of IL4 and other cytokines in T helper cell development in an
      alpha beta TCR transgenic mouse system.

PMID- 8303081
TI  - The anti-tumour and proinflammatory actions of IL4.

PMID- 8303082
TI  - Interleukin-4-deficient mice.

PMID- 8303083
TI  - Regulatory and immunopathological roles of IL4 in experimental schistosomiasis.

PMID- 8303084
TI  - In vitro and in vivo effects of quinidine on the kidneys in Fischer-344 rats.
AB  - Quinidine in vitro significantly reduced accumulation of TEA (tetraethyl
      ammonium) and PAH (p-amino hippurate) and inhibited oxygen consumption in renal
      cortical slices. Mitochondrial respiratory control index (RCI) and ADP/O ratio
      were decreased. Intraperitoneal administration of quinidine at 75 mg/kg twice a
      day for four days inhibited TEA transport in renal cortical slices and decreased
      oxygen consumption. Mitochondria showed a reduction in ADP/O ratio but no change
      in RCI. Serum biochemical measurements indicated a significant elevation in serum
      creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST).

PMID- 8303085
TI  - Antioxidant and pro-oxidant assay for a new drug GEPC: detected by ESR
      spectrometry and by protective effects on lipid peroxidation and biomolecule
      degradation.
AB  - L-Ascorbic acid 2-(20 beta-11-oxo-olean-12-en-29-oic acid ethylester-3-beta-yl
      hydrogen phosphate) sodium salt (GEPC) is a newly synthesized compound
      representing a phosphate diester linkage of glycyrrhetic acid ethylester and
      ascorbic acid. In the present study, we found that GEPC effectively inhibited
      Fe(III)-ADP/NADPH-induced peroxidation of liver microsomes. The inhibitory effect
      was much greater than that of glycyrrhetic acid (GA), and contrasted with the
      stimulatory effect of ascorbic acid. An ESR study showed that GEPC appeared to
      have a great loss of the DPPH and superoxide radical scavenging effects of
      ascorbic acid. However, GEPC, like ascorbic acid, inhibited hydroxyl radicals
      generation in both Fe(II)-H2 O2 and Cr(VI)-H2 O2 systems. GEPC, unlike ascorbic
      acid, showed no pro-oxidant effect and acted as an effective iron-chelating agent
      in the ESR study or in the iron-induced deoxyribose and DNA degradation assays.
      The hydroxyl radical scavenging effect of GEPC was further demonstrated by its
      protective effect on the hydroxyl radical- induced degradation of certain
      biomolecules, i.e., carbohydrates, amino acids, and DNA. These results
      demonstrate that beside its protective effect on ascorbic acid autoxidation and
      increasing water solubility of GA, GEPC is also an antioxidant though not so
      powerful as ascorbic acid but more powerful than GA.

PMID- 8303086
TI  - TMB-8 and thapsigargin modulate purine release from dissociated primary cultures
      of rat brain astrocytes.
AB  - In our previous studies, the evoked purine outflow from rat brain cultured
      astrocytes was reported to be Na+ independent and K+ and [Ca2+]e partially
      dependent. Thus, the eventual [Ca2+]i influence on purine astrocyte release was
      investigated in an attempt to better characterize the ionic requirements of this
      mechanism in cells which serve many complex and still partly unknown functions
      within the CNS. TMB-8 and Thapsigargin (drugs described as able to inhibit and
      increase the ion efflux from its internal stores respectively) and BAPTA/AM (able
      to chelate the cytoplasmic free Ca2+), were used. TMB-8 and BAPTA/AM decreased,
      whereas Thapsigargin enhanced glial purine outflow. These findings suggest a
      significant [Ca2+]i dependence of the electrically evoked purine efflux from
      cultured astrocytes even though further investigations using fluorescent probes
      are needed.

PMID- 8303087
TI  - The inhibitory effects of salmon calcitonin on intrathecally-injected N-methyl-D
      aspartate-induced aversive behavior in mice.
AB  - The effects of salmon calcitonin (SCT) on intrathecally-injected N-methyl-D
      aspartate (NMDA)-induced aversive behavior were investigated to clarify the
      involvement of the NMDA receptor/ionophore complex on the analgesic effects of
      SCT. Intracerebroventricular (i.c.v.) injection of SCT significantly inhibited
      acetic acid-induced writhing. Intrathecal (i.t.) injection of NMDA (0.25-1.0
      nmol/mouse) dose-dependently induced aversive behavior such as scratching and
      tail biting. SCT at the doses of 0.01 and 0.1 IU/mouse (i.c.v.) significantly
      inhibited the NMDA-induced aversive behavior. This inhibitory effects of SCT on
      NMDA (i.t.)-induced aversive behavior were neither potentiated nor antagonized by
      i.c.v. injection of MK-801 and NMDA, respectively. Further, MK-801 (i.c.v.) and
      NMDA (i.c.v.) themselves did not affect the NMDA (i.t.)-induced aversive
      behavior. These results suggest that the NMDA receptor/ionophore complex in the
      brain is not directly involved in the antinociceptive effects of intracerebrally
      injected SCT.

PMID- 8303088
TI  - Improvement of the energy status of hypoxic hepatocytes by calcium channel
      blockers.
AB  - Isolated hepatocytes from rat liver in primary culture rapidly lost viability
      under hypoxic conditions. Hypoxic injury was significantly decreased by the
      calcium channel blockers nifedipine (5 microM) and diltiazem (10 microM). The
      concentrations of the inhibitors which afforded maximum protection also produced
      the maximum increase in the energy level of the hypoxic hepatocytes, as evidenced
      by their ATP, ADP, AMP, and total adenine nucleotide content and by their energy
      charge. The increased hypoxic energy level caused by these calcium channel
      blocking agents was not due to an increased rate of anaerobic glycolysis;
      nifedipine did not have any effect on lactate production while diltiazem slightly
      decreased its rate. During the first 2 h under hypoxic conditions the cytosolic
      Ca2+ concentration remained constant around 100 nM, subsequently increasing to
      400 nM first slowly and later more rapidly. The calcium channel blockers delayed
      the Ca2+ increase by about 1 h but were without any effect on the rate of this
      increase. The results suggest that the well-known beneficial effects of calcium
      channel blockers on hypoxic liver injury are due in large measure to an improved
      energetic situation of the hepatocytes rather than to the increase in the
      cytosolic Ca2+ concentration being blocked.

PMID- 8303089
TI  - Changes in hepatic copper distribution leading to hepatitis in LEC rats.
AB  - Copper (Cu) accumulating in the liver of LEC (Long-Evans with a cinnamon-like
      coat color) rats due to a hereditary metabolic disorder is assumed to cause acute
      hepatitis with severe jaundice or chronic hepatitis leading to cancer. Changes in
      concentrations and distributions of Cu, zinc and iron in the liver of LEC rats
      were determined to find the relationship between the chemical forms and the
      toxicity. Female rats after delivery were used because of high susceptibility to
      acute hepatitis. They were divided into four stages according to the development
      of jaundice. Cu concentrations in the whole liver and the supernatant decreased
      with development of jaundice. Distribution profiles of Cu, zinc, iron and sulfur
      on a gel filtration column by HPLC-ICP showed that Cu in the liver supernatant
      was mostly bound to metallothionein (MT) before jaundice (stage 1), high
      molecular weight proteins and MT at the beginning of jaundice (stages 2 and 3),
      and then mostly to MT at severe jaundice (stage 4) though the concentration of Cu
      at this stage was decreased to about 50% of stage 1. The results suggest that Cu
      accumulating as MT in the liver is liberated drastically after exceeding the
      capacity of MT synthesis, and the liberated Cu causes acute hepatitis.

PMID- 8303090
TI  - Changes in copper distribution in the plasma and kidneys of LEC rats following
      acute hepatitis.
AB  - Copper (Cu) accumulating bound to metallothionein (MT) in the liver of LEC (Long
      Evans with cinnamon-like coat color) rats due to a hereditary metabolic disorder
      is assumed to lead to acute hepatitis with severe jaundice. The metal was shown
      to be present in the liver in a form not bound to MT at the beginning of
      hepatitis after first delivery and lactation. Following this change in the
      distribution of Cu from MT-bound to non-MT bound form in the liver, changes in
      the concentrations and distributions of Cu, zinc (Zn) and iron in the plasma and
      kidneys of LEC rats were also observed. Cu plasma distribution on a gel
      filtration column by HPLC-ICP revealed that the holo-form of ceruloplasmin (Cp)
      was present before hepatitis and increased with its development, indicating the
      availability of Cu for Cp by hepatitis. Cu-binding proteins migrating at the same
      retention times as those of hepatic Cu-MT and Cu,Zn-superoxide dismutase (SOD)
      were detected in plasma during hepatitis. Albumin was largely present in the form
      of nonmercaptoalbumin, reflecting that the bloodstream was under oxidative
      stress. A sudden increase in the concentration of Cu in the kidneys occurred with
      hepatitis, and the metal came to be distributed more to high molecular weight
      proteins with its development.

PMID- 8303091
TI  - Carbon tetrachloride promoted malondialdehyde formation in liver microsomal and
      nuclear preparations from Sprague Dawley or Osborne Mendel male rats.
AB  - CCl4 is a hepatic carcinogen in male Osborne-Mendel (OM) but not in Sprague
      Dawley (SD) male rats. We demonstrate the occurrence of NADPH-dependent CCl4
      promoted lipid peroxidation processes (LP) leading to malondialdehyde (MDA)
      formation in liver microsomal and nuclear preparations from OM and SD rats which
      do not correlate with the cancer susceptibility of both strains. Our results
      suggest that MDA production might not be a rate determining step in the
      carcinogenic process. However, the formation of this reactive aldehyde proximal
      to DNA and nuclear proteins might play a role that remains to be elucidated.

PMID- 8303092
TI  - Protective effect of dantrolene sodium on carbon tetrachloride induced liver
      injury in the rat.
AB  - The effect of dantrolene sodium on liver injury induced by CCl4 was investigated
      in the rat. Liver microsomal P-450 and b5 levels, serum triiodothyronine levels
      (T3), and alanine aminotransferase activity (ALT) were measured over 4 to 16 h
      after CCl4 (0.2 ml/kg, s.c.) administration. Serum ALT rose following CCl4
      administration, while liver cytochrome P-450 and b5 levels and serum T3 which
      reflects the liver microsomal thyroxine-5'-deiodinase activity (1) fell.
      Intraperitoneal administration of dantrolene sodium (5 mg/kg), 1 h before CCl4
      s.c., suppressed CCl4-induced elevation of the serum ALT significantly. However,
      levels of P-450, b5, and serum T3 were not significantly different between
      dantrolene-treated and untreated groups. These results suggest that dantrolene
      sodium has a protective effect on CCl4-induced liver injury through a mechanism
      unrelated to these liver microsomal functions.

PMID- 8303093
TI  - Urinary proteoglycans after cadmium exposure.
AB  - The excretion of urinary glycosaminoglycans by five occupationally exposed men
      with urinary cadmium levels of 1 to 6.5 micrograms/g creatinine did not differ
      significantly from that of six age-matched non-exposed controls (2.8 +/- 1.8
      mg/mmol creatinine vs. 2.3 +/- 1.6 mg/mmol creatinine, +/- S.D.) as analyzed in
      random urine samples. However, there was a cadmium concentration-dependent
      increase in the excretion of 50 kD proteoglycan as analyzed by polyacrylamide
      electrophoresis of the isolated proteoglycan fraction in the same urine samples.
      This may represent the early dose-dependent effect of cadmium on renal tubules
      which leads to decrease in the renal cell sialic acid content and protein
      excretion at higher exposure levels.

PMID- 8303094
TI  - Active oxygen formation in alveolar macrophage and pulmonary tumorigenesis.
AB  - Glycerol enhances pulmonary tumorigenesis in mice treated with 4-nitroquinoline 1
      oxide (4NQO). In order to evaluate factors that contribute to the enhancing
      effect of glycerol on 4NQO-induced pulmonary tumorigenesis, we selected alveolar
      macrophage (AM) as a source of active oxygen formation in the lung and
      investigated the effects of glycerol on active oxygen formation in AMs treated
      with 4NQO. AMs were stimulated with opsonized zymosan, and active oxygen
      formation in AMs was examined after stimulation. Continuous glycerol treatment
      within 4 weeks after 4NQO injection has no influence on the capacity of active
      oxygen generation in AMs (expressed as maximum count of chemiluminescence) and
      the total amount of active oxygen generation in AMs (expressed as total count of
      chemiluminescence). These results suggest that active oxygen formation in AMs
      does not contribute to enhance 4NQO-induced pulmonary tumorigenesis in mice
      treated with glycerol.

PMID- 8303095
TI  - Immunoreactive hepatocyte growth factor is present in tissue extracts from human
      breast cancer but not in conditioned medium of human breast cancer cell lines.
AB  - Hepatocyte growth factor (HGF) is a novel mitogen for mature hepatocytes. In the
      present study, we have measured immunoreactive (ir)-HGF concentration in tumor
      extracts of 82 primary human breast cancers using an enzyme-linked immunosorbent
      assay (ELISA). Ir-HGF was detectable in all tissue extracts, the concentration
      ranging from 1.4 to 306.5 ng/100 mg protein (median value: 11.2 ng/100 mg
      protein). Correlation analyses between ir-HGF concentration and
      clinicopathological factors showed that the ir-HGF level was significantly higher
      in tumors with sizes of more than 5.0 cm compared with those less than 5.0 cm. In
      contrast, no detectable amount of ir-HGF was secreted into culture medium of two
      breast cancer cell lines, MCF-7 and ZR-75-1, suggesting that the cancer cell
      itself has no ability to produce ir-HGF.

PMID- 8303096
TI  - Melatonin receptors in purified cell nuclei of liver.
AB  - Specific binding of [125I]iodomelatonin to homogenates from purified rat liver
      nuclei was characterized. The binding is rapid, reversible, saturable and of high
      affinity. Specific binding seems to be found in the nuclear protein fraction,
      since after precipitation of the proteins with trichloroacetic acid, the specific
      binding disappeared. The Kd (180 +/- 20 pM) and Bmax (9.1 +/- 0.03 fmol/mg
      protein) values (mean +/- S.E.M.) agree with the melatonin concentration in
      nuclei and may imply a physiological locus for melatonin action.

PMID- 8303098
TI  - Incisional versus excisional biopsy.

PMID- 8303097
TI  - Advantages and disadvantages of cytology and histopathology for the diagnosis of
      cancer.
AB  - Histopathology and cytology are both valuable diagnostic tools. An appreciation
      of the virtues and the limits of each technique is essential if the user is to
      avoid mistakes in interpretation. It is also important to take full advantage of
      the many additional techniques that can be applied to cytology smears and
      histopathology tissue sections to gain maximum clinical information.

PMID- 8303099
TI  - Biopsies of the skin and mucous membranes.
AB  - A skin or mucous membrane biopsy is an important diagnostic technique in
      veterinary dermatology. Careful thought must be given in the selection of which
      animal patients to biopsy and what lesions to biopsy. Care must be taken in
      performing the biopsy to avoid traumatic artifacts that make interpretation
      difficult for the pathologist. Finally, histological findings are just one
      assessment and must be coupled with a thorough history, physical examination, and
      other laboratory findings before a definitive diagnosis is offered.

PMID- 8303100
TI  - Gastrointestinal endoscopic biopsy techniques.

PMID- 8303101
TI  - Bone biopsy.
AB  - Neoplasia is the most common cause of bone lesions in small animals. A definitive
      diagnosis is required to determine an accurate prognosis and to formulate
      effective treatment options. Each lesion should be characterized as accurately as
      possible by evaluation of patient history, signalment, laboratory findings, and
      the radiographic appearance and location of the lesion. A bone biopsy is
      recommended for lesions that require histological characterization or culture and
      susceptibility testing. The biopsy technique of choice should be properly planned
      to provide accurate sampling of the lesion, to produce the least morbidity
      possible, and to avoid interferences with future surgical treatment.
      Approximately 94% of lesions can be definitively diagnosed on the first biopsy
      attempt if the center of the lesion and the transitional zone between the lesion
      and normal bone are accurately sampled. Use of a guide wire and prebiopsy
      radiographs help ensure accurate sampling. A diagnosis of reactive bone is
      usually an indication for a second biopsy or for close clinical and radiographic
      monitoring of the lesion.

PMID- 8303103
TI  - Image-guided percutaneous needle biopsy: ultrasound, computed tomography, and
      magnetic resonance imaging.

PMID- 8303102
TI  - Biopsy and cytological sampling of the respiratory tract.

PMID- 8303104
TI  - Marking margins of tumorectomies and excisional biopsies to facilitate
      histological assessment of excision completeness.
AB  - Assessment of tumor margins for completeness of excision is important for local
      control of neoplastic masses, particularly those that are potentially curable
      with surgery. Of the margin-marking techniques available, India inking seems to
      be the most practical way for veterinary clinicians to help pathologists
      accurately distinguish between surgical margins and margins created during sample
      processing. India inking prevents misinterpretation of contaminated processing
      margins as inadequate surgical excisions; however, a strongly definitive decision
      that an excision is complete cannot be made with any margin-marking technique
      because it is impossible to examine the entire surface of every margin.

PMID- 8303105
TI  - Biopsies from the pathologist's point of view.

PMID- 8303106
TI  - Interpreting the pathologist's report.
AB  - It is imperative that the clinician/practitioner and diagnostic pathologist
      communicate. Both individuals practice their profession with innate professional
      biases based on training and experience. Like clinical medicine, pathology is a
      professional art and is subject to interpretative variance. When the clinician
      receives a pathological report that does not agree with the clinical
      presentation, there is an obligation to communicate the concern to the
      pathologist and request a second opinion or agree on the need for submission of
      additional biopsy material.

PMID- 8303107
TI  - Dental operatory design and equipment.

PMID- 8303108
TI  - [Prevention of digestive hemorrhage recurrence in hepatic cirrhosis with
      propranolol. A 4 years' follow-up study].
AB  - The aim of this study was to assess the effect of propranolol treatment on the
      recurrence of variceal bleeding and mortality in patients with hepatic cirrhosis.
      Fifty seven patients were studied; they were recruited within 15 days of an
      episode of variceal bleeding, assigned randomly to receive propranolol (n = 29)
      placebo (n = 28) and followed during 4 years. Three patients were lost from
      follow up and in 3 propranolol was discontinued due to secondary effects.
      Bleeding recurrence was less frequent in the treated patients (Kaplan Meier
      analysis p < 0.01). Ten patients on placebo and 1 receiving the active drug died.
      Life table analysis showed a significantly better survival in the group of
      patients treated with propranolol. It is concluded that propranolol decreases the
      recurrence of variceal bleeding and improves survival in patients with hepatic
      cirrhosis.

PMID- 8303109
TI  - [Morphology of the myenteric plexus of the small intestine in patients with liver
      cirrhosis].
AB  - BACKGROUND: Patients with liver cirrhosis develop small bowel dysmotility of
      unknown etiology. Morphological features in the enteric nervous system and the
      intestinal smooth muscle may shed light on pathophysiology of the gut motility
      disturbances in this disease. AIM: To investigate the morphology of the myenteric
      plexuses and smooth muscle layers of the small intestine in patients with liver
      cirrhosis. PATIENTS AND METHODS: Full thickness biopsies of duodenum, jejunum and
      ileum from seven cirrhotic patients and seven controls were stained with several
      techniques, including silver impregnation. Neuronal counting and light microscopy
      studies were stained performed. RESULTS: The neuronal count was not significantly
      different in patients with cirrhosis compared to controls in duodenal samples
      (1.6 +/- 0.4 cel/mm vs 1.6 +/- 0.2 cel/mm), jejunal tissue (1.2 +/- 0.3 cel/mm vs
      1.4 +/- 0.2 cel/mm), and in ileal specimens (0.8 +/- 0.3 cel/mm vs 0.9 +/- 0.2
      cel/mm). In both groups, evidence of fibrosis or inflammation in myenteric
      plexuses and in smooth muscle was not found. Also, intestinal neuronal dysplasia
      was absent in cirrhotic patients as in controls. CONCLUSION: These results
      suggest that small bowel dysmotility in patients with liver cirrhosis is not
      related to structural changes in myenteric plexuses or in intestinal smooth
      muscle noted by light microscopy.

PMID- 8303110
TI  - [Soft tissue sarcoma. Combined treatment of drug therapy, radiotherapy and
      conservative surgery].
AB  - The preliminary results of a prospective and cooperative protocol for the
      treatment of soft tissue sarcomas of trunk and extremities, stages IB-IIIB are
      presented. Thirty one patients (17 males, 22 with a tumor larger than 5 cm) aged
      16 to 68 years, were treated with one dose of epirubicin 70 mg/m2 i.v. and
      radiotherapy (3000 rads in 10 fractions) Two or three weeks later an ample
      surgical complications occurred in 6 patients and were all of infectious origin.
      The median follow up period has been of 26 months. During this period 5 patients
      presented late surgical complications (edema in 4 and a pathological fracture in
      1), 2 patients had a local tumor recurrence and distant metastases appeared in 7.
      Actuarial survival was 60% at 48 months. Ninety six percent of surviving patients
      conserved their extremity. It is concluded that with this treatment modality
      local recurrence is acceptable, morbidity is low and that the majority of
      patients do not require amputations or crippling resection.

PMID- 8303111
TI  - [Systemic lupus erythematosus: valvular regurgitation and its relation to
      anticardiolipin antibodies].
AB  - The aim of this study was to assess the relationship between the incidence and
      severity of valvular regurgitation and the presence of high levels of
      anticardiolipin antibodies in a group of patients with systemic lupus
      erythematosus. Fifty patients aged 35.5 +/- 13.4 years and 84 healthy age and sex
      matched controls were studied with two dimensional echocardiography with color
      flow imaging. IgG and IgM anticardiolipin antibodies were measured in all
      patients within a week of the echocardiographic study. Patients had a similar
      incidence of aortic, tricuspid and pulmonic regurgitation than normals. However
      there was a greater incidence of mitral regurgitation among patients (56 vs 21% p
      < 0.001). The seven patients with moderate or severe mitral regurgitation had
      Libman Sacks vegetations of the valve. Twenty five of 28 patients with mitral
      regurgitation had increased anticardiolipin antibodies; moreover, these levels
      were significantly higher among patients with mitral regurgitation and thickened
      mitral valves than those with normal valves. Patients with increased
      anticardiolipin antibodies had a higher incidence of Libman Sacks vegetations. No
      association between the presence of these antibodies and the severity of aortic,
      pulmonic or tricuspid regurgitation was observed. It is concluded that the
      incidence of mitral valve regurgitation is increased in systemic lupus
      erythematosus and related to raised anticardiolipin antibodies.

PMID- 8303112
TI  - [Crohn's disease: clinical presentation and results of surgical treatment].
AB  - Surgery has an important role in the treatment of Crohn's disease (CD). The
      objective of this communication is to assess the results of surgical treatment in
      CD, trying to identify recurrence risk factors. A retrospective review of the
      charts of 120 patients with CD seen between 1963 and 1990 was made. One third of
      these patients required surgical treatment. The series was divided in two groups.
      Group A comprised patients treated from 1963 to 1977. Of these, 30% had ileal
      localization of the disease and 20 patients were submitted to 20 surgical
      procedures. The major surgical indication was intestinal obstruction and
      resection was performed in 85% of patients. Morbidity was 20% and mortality 10%.
      Group B comprised patients treated from 1978 to 1990. Nineteen patients were
      submitted to 22 surgical procedures. The disease was localized in the ileon in
      50% of these patients. Twenty one surgical procedures were resective with a 9%
      complication rate and no surgical mortality. Eighty percent of patients in this
      group has a complete follow up. In 47% the disease recurred 37 months (as a mean)
      after surgery. No effect of age, sex or localization of the disease on the risk
      of recurrence was observed. It is concluded that morbidity and mortality of
      surgical treatment for Crohn's disease has decreased and a prolonged control of
      symptoms has been achieved. No recurrence risk factors were identified in this
      study.

PMID- 8303113
TI  - [Yield of myocardial perfusion study with Thallium 201 in coronary artery
      disease: planar analysis].
AB  - The yield of exercise thallium-201 scintigram was studied in a group of 101
      patients with suspected coronary artery disease or with a history of an old acute
      myocardial infarction. The thallium perfusion imaging was performed with planar
      technology and was interpreted visually. Its results were compared with
      conventional exercise testing and the results of a coronary arteriography
      performed within 30 days. Global sensitivity for conventional exercise testing
      was 60.4%, which increased to 78.2% with the thallium study. Specificity was
      raised from 47.2 to 84.8%. In patients with one, two or three vessel disease,
      thallium scintigram was abnormal in 95.1%, 96.6% and 100% respectively (NS).

PMID- 8303114
TI  - [Amenorrhea, insulin resistance and acanthosis nigricans. A hyperandrogenic and a
      normoandrogenic clinical forms].
AB  - Two cases of HAIR-AN syndrome (hyperandrogenism, insulin resistance and
      acanthosis nigricans) are presented. The first case corresponds to a female with
      a systemic lupus erythematosus and acanthosis nigricans in which an insulin
      resistance was documented; the patient was in amenorrhea with severe
      hypoestrogenism, although she did not have clinical signs of hyperandrogenism and
      serum androgen levels were normal. This case corresponds to a HAIR-AN syndrome
      associated to autoimmune diseases or type A of Kahn. The second case is a young
      female with clinical signs of hyperandrogenism associated to high testosterone
      levels; she had acanthosis nigricans and fasting and postprandial
      hyperinsulinemia. Probably, this case corresponds to a type A or C HAIR-AN
      syndrome in which there is a decrease in the number of insulin receptors or a
      post receptor defect in insulin action.

PMID- 8303115
TI  - [Neuroacanthocytosis: report of 3 cases].
AB  - Neuroacanthocytosis is a syndrome characterized by extrapyramidal neurologic
      manifestations such as chorea, dystonia, parkinsonism or tics and acanthocytosis
      in the blood smear. It is often associated with self aggression (lips and tongue
      bites) and arreflectic amyotrophy of the extremities. Three adult patients with
      the characteristic neurologic manifestations of the syndrome, acanthocytosis in
      the blood smear and normal plasma lipoproteins are presented. Kell antigen was
      negative in all the patients. Two patients presented as a Gilles de la Tourette
      syndrome and one as a familiar Chorea. The diagnosis must be suspected in adult
      patients with extrapyramidal manifestations and in whom the blood smear shows the
      presence of acanthocytosis. This is the first report of neuroacathocytosis in
      Chile and the second in a group of patients of hispanic origin.

PMID- 8303116
TI  - [Ethical principles to investigate the human genome].
AB  - The scientific community is becoming aware that mankind has started to directly
      manipulate the mechanisms that transmit life and guide our species evolution.
      These facts are overflowing the traditional concepts about humanism and medical
      ethics, with an unpredictable scope. Presently we are conscious that there is an
      universal and biological order that rules life in our planet. At the molecular
      level there is an hereditary order and scientists have established the "central
      dogmas" of molecular biology and "genetic creed" of Mendelian theory in
      population genetics. The biotechnological revolution of the last decades is
      dismantling the normal processes of biological balance through the early
      detection and healing of defects, the manipulation of reproduction and the
      rupture of species boundaries with interspecies hybridization. All these issues
      open debates about the ethical limits of scientific research freedom. As a
      consequence, the dictation of genetic ethical codes has been proposed and
      statements that restrain genic therapy methods, genetic heritage manipulation and
      the patent right for DNA sequences, have been approved. The Valencia Statement
      (1990) on ethics about human genome tries to conciliate and establish a minimal
      consensus among scientists. However it seems that we are tearing down the
      frontiers that keep the sanctuary of biological order closed and damaging the
      twentieth century science dogmas.

PMID- 8303117
TI  - [Insulin resistance: a frequent phenomenon in clinical practice].
AB  - This review is focused on the diagnostic, clinical and therapeutic aspects of
      insulin resistance relevant to the clinician. The observed phenomenon of the wide
      variability of insulin sensitivity in clinically healthy subjects is discussed;
      qualitative and quantitative aspects of the methodologies currently used for the
      assessment of insulin sensitivity in the clinical setting are dealt with, as well
      as their applicability to day-to-day clinical care. The medical consequences of
      hyperinsulinemia, including dyslipidemia, hypertension coronary artery disease
      and ovarian hyperandrogenism are likewise discussed. A panoramic view of the
      various clinical presentations of insulin resistance is also offered, including
      clinical elements for suspicion, as well as an account of the prevalent, less
      prevalent and rare disorders harboring the phenomenon of insulin resistance. The
      final topic of the review is a novel discussion on the therapeutic possibilities
      in insulin resistance disorders, including treatment with hormones and
      antihormones.

PMID- 8303118
TI  - [Insulin resistance].
AB  - Peripheral insulin resistance with normal glucose homeostasis and compensatory
      hyperinsulinemia is a common feature of a series of conditions. It is usually
      present in obesity and initiates the events leading to non insulin dependent
      diabetes. It is also pathogenetically related to hypertension, dyslipidemias and
      clinical atherosclerosis, diseases that are frequently associated between them.
      Although its etiology remains partially unknown, strong evidences suggest that it
      is due to a post receptor defect, involving the intracellular signals that drive
      carbohydrate metabolism. This explains the preservation of other insulin actions
      and the effect of hyperinsulinemia on hypertension, dyslipidemia and
      atherogenesis. In obesity, the increased lipid oxidation and serum free fatty
      acid levels, inhibit enzymes and cofactors involved in carbohydrate metabolism.
      This leads to a reduction in glucose disposal and increases hepatic glucose
      output, outlining a post receptor defect leading to insulin resistance.

PMID- 8303119
TI  - [Purulent meningitis: a long-standing problem].
AB  - Bacterial meningitis is a problem for Public Health that has to be reviewed
      periodically. Most of the infections are due to Meningococcus, Haemophilus
      influenzae or Streptococcus pneumoniae. Seventy per cent of the cases are seen in
      children less than 5 years old; mortality ranges between 5% to 20% of the
      patients. Progress has been made with vaccination for Meningococcus types A and C
      and for H influenzae type B. In Chile, meningococcal meningitis is endemic, with
      epidemic bouts in the north part of the country. Currently, studies are in
      progress in Santiago with vaccination against H influenzae type B, in the hope
      that it can be extended to the rest of the country.

PMID- 8303120
TI  - [University students and sex: what they think, what they know, what they do].
AB  - Using the social survey technique, a random sample of 464 students from the
      Universidad Austral answered a structured questionnaire about behavior and
      attitudes towards sex. Results show that the majority of students have had sexual
      experiences. Men and women differ significantly in motivations and age at the
      start of their sexual activity, stability of their relationships, first sexual
      partner and emotional experiences. Sexual behavior is associated with age, years
      of university studies and geographical origin. On the contrary this behavior is
      weakly influenced by religion or family. Premarital sexual intercourse is
      accepted by the majority of students. Knowledge about sexual physiology and
      contraception is scarce in 30 to 80% of students. It is concluded that, since a
      great number of students have an active sexual life along with little knowledge
      in this topic, the University has to assume an active role in the sexual
      education of students.

PMID- 8303121
TI  - [Epidemiologic and nutritional characteristics of the elderly].
AB  - A sample of 1365 elders of both sexes from rural and urban populations was
      studied. Thirty four percent of the subjects were older that 80 years. 21.6%
      lived alone, 25% were illiterate and 50% did not finish elementary school. Mental
      impairment was found in 5.6% and body mass index was normal in 41.4% of subjects.
      Eighty seven percent did not smoke and 80% were teetotalers. Medical services
      were requested at least every one year by 15.4% and twice a year by 11.9% of
      subjects. These numbers will help to design preventive and interventional
      policies directed to this segment of the population.

PMID- 8303123
TI  - [Non-traditional hospital implementation. Experience of a rural hospital].

PMID- 8303122
TI  - [Cyclosporine, blood transfusions, and renal transplantation].

PMID- 8303124
TI  - [Learning preferences in students of a Children medical school. Longitudinal
      study].
AB  - In a longitudinal study, a sample of 16 first year medical students of
      Universidad de La Frontera medical school was selected initially. The sample was
      stratified in two groups according to the academic results obtained at the end of
      the first semester. The aim of the study was to determine if the exposure to a
      traditional teaching methodology during 5 years causes changes in learning
      preferences that were detected at the beginning of the career. The Rezler self
      report inventory for learning preferences was applied to all the students in two
      opportunities: at the end of the first academic semester and after finishing the
      first five years of undergraduate training. The obtained results show a dynamic
      behavior or students preferences in both groups. At the beginning and end of the
      study a predominance of subcategory "concrete" is seen in both groups. The
      students belonging to the category "interpersonal" at the beginning of the study,
      changed posteriorly to the subcategory "individual", which also finally
      predominated in both groups.

PMID- 8303125
TI  - [Follow-up of a patient].

PMID- 8303126
TI  - [Peroperative anesthesia].

PMID- 8303127
TI  - [Role of the nurse in the removal of brain metastases under stereotaxic
      guidance].

PMID- 8303128
TI  - [Stereotaxic techniques].

PMID- 8303129
TI  - [Imaging of cerebral metastases].

PMID- 8303130
TI  - [Treatment of bone metastases].

PMID- 8303131
TI  - [Postoperative monitoring of a patient operated for a cerebral metastasis].

PMID- 8303132
TI  - [Endoprosthesis of the bile ducts. Taking charge of the patient].

PMID- 8303134
TI  - [The thyroid gland. Basedow's disease].

PMID- 8303133
TI  - [Intracranial anatomy].

PMID- 8303135
TI  - [Monitoring of the intracranial pressure].

PMID- 8303136
TI  - [Epidemiology and biology of cerebral metastases].

PMID- 8303137
TI  - [Taking charge of the patient before the intervention].

PMID- 8303138
TI  - Is walking sufficient exercise for health?

PMID- 8303139
TI  - Physiological responses to deep water running in athletes.

PMID- 8303140
TI  - Nutritional practices of elite athletes. Practical recommendations.
AB  - The nutritional intake of elite athletes is a critical determinant of their
      athletic performance and ability to compete both physically and mentally.
      However, their demanding training and travel schedules in addition to a possible
      lack of nutritional knowledge may prohibit them from maintaining an optimal
      dietary intake. Sound scientific data about the nutritional habits of elite
      athletes are limited and, therefore, it is not clear as to whether elite athletes
      are following nutritional recommendations and maintaining nutritionally sound
      diets. This review takes a comprehensive look at 22 recent dietary intake
      studies, including 50 groups of elite athletes. The time period for food record
      collection ranged from 3 to 7 days except for 2 studies which collected records
      for 21 and 22 days. Energy intakes of > 50 kcal/kg/day for male athletes who
      train for > 90 min/day and 45 to 50 kcal/kg/day for female athletes training for
      > 90 min/day are recommended. Bodyweight should be monitored frequently as a
      check on calorie intake. With a sufficient calorie intake (1.2 to 2.0 kg/kg/day)
      protein supplementation is not necessary. Ingested carbohydrate stored as
      glycogen serves as the primary fuel for muscle performance. Athletes in training
      should consume 70% of total calories as carbohydrate. Athletes on low energy
      diets (< 2200 kcal/day) should have a diet of < 25% fat, and athletes with large
      energy needs should consume 30% fat in their diet. In general, fat intakes should
      be reduced and carbohydrate intakes increased. Athletes should also restrict
      alcohol intake during training and competition periods. Athletes with low calorie
      intakes should consume foods with high contents of iron, calcium, magnesium, zinc
      and vitamin B12. Athletes with high calorie intakes should consume foods that are
      naturally high in or fortified with B-group vitamins. Fluid, electrolyte and
      energy supplementation is desirable to support circulatory, metabolic and
      thermoregulatory functions. There is no special food that will help elite
      athletes perform better; the most important aspect of the diet of elite athletes
      is that it follows the basic guidelines for healthy eating.

PMID- 8303141
TI  - Effect of the different phases of the menstrual cycle and oral contraceptives on
      athletic performance.
AB  - The female athlete, during her reproductive years, has a complex and ever
      changing milieu of female steroid hormones, whether it is the endogenous
      variations in estradiol and progesterone of a regular menstrual cycle, or the
      exogenous synthetic hormones of the oral contraceptives. Both estrogens and
      progestins have individual, interactive and sometimes opposing physiological
      actions with potential implications for the exercising female. In retrospective
      surveys on the menstrual cycle and performance, from 37 to 63% of athletes did
      not report any cycle 'phase' detriment, while 13 to 29% reported an improvement
      during menstruation. The best performances were generally in the immediate
      postmenstrual days, with the worse performances during the premenstrual interval
      and the first few days of menstrual flow. However, this type of study has an
      inherent built-in bias, and is further limited by the lack of substantiation of
      cycle phase. Many of the women studied associated premenstrual symptoms, such as
      fluid retention, weight gain, mood changes, and dysmenorrhoea with performance
      decrement. Such factors have also been causally linked with an increase in
      traumatic musculoskeletal injuries during the premenstrual and menstrual period.
      Neuromuscular coordination, manual dexterity, judgement and reaction time for
      complex tests have been shown to be adversely affected in women with premenstrual
      syndrome or symptoms, but confounding variables may include nutrition status and
      blood sugar levels. In addition, not all women suffer to the same level with
      premenstrual symptoms. Fluctuations in many physiological functions occur
      throughout the normal menstrual cycle. Results of early studies are difficult to
      interpret owing to the small numbers of women studied, wide range of fitness
      levels, and variability in the definitions of cycle phase. Nevertheless,
      investigators did not document any significant changes in measures of athletic
      performance as a function of timing of testing during the menstrual cycle.
      Swimmers have shown a premenstrual worsening of performance times, with
      improvement during the menstrual phase and on the eighth day of the cycle. An
      increase in perceived exertion was noted premenstrually and during the early
      menstrual stage with very intense exercise. In cross-country skiers, the best
      times were recorded in the postovulatory and postmenstrual phases, prompting the
      recommendation that training loads be selected according to cycle phase to
      achieve maximum benefit. Investigations using estradiol and progesterone levels
      as a confirmatory index of ovulation have not generally found significant
      differences across the cycle in either maximal or submaximal exercise responses,
      although a slight decrease in aerobic capacity during the luteal phase has been
      reported.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8303144
TI  - The breast test on trial.

PMID- 8303143
TI  - Patellofemoral stress syndrome. Current concepts.
AB  - Patellofemoral stress syndrome is a condition of peripatellar pain without
      anatomic malalignment, history of trauma, patellar instability or clinical
      evidence of patellofemoral crepitus. These patients demonstrate lateral
      retinacular and iliotibial band tightness. Frequently, the patient's pain occurs
      when sitting for prolonged periods of time with the knee flexed, and most
      commonly with sporting events. A complete history and physical evaluation is
      necessary for an accurate diagnosis. This evaluation should include the following
      radiographs: anterior-posterior, lateral, and most importantly, the tangential
      views. Once diagnosed, patellofemoral stress syndrome is usually treated
      conservatively. Studies indicate that 60 to 80% of knees will respond favourably
      to conservative treatment. The exercise programme should include iliotibial band
      stretching, hamstring stretching, gastrocnemius stretching, progressive
      resistance straight leg raising and hip adduction strengthening. These exercises
      should be performed 2 times/day until symptoms subside and then 3 times/week as
      long as the patient is active in sports. If the conservative programme fails,
      surgical management may be considered. A lateral retinacular release or possibly
      lateral retinacular lengthening are surgical procedures recommended as reliable
      solutions in the majority of patients. These procedures require continuation of
      the exercise programme to be successful.

PMID- 8303145
TI  - Diploma level courses: nurse teachers' initial perceptions.

PMID- 8303142
TI  - Short term effects of exercise on plasma lipids and lipoproteins in humans.
AB  - Lipids and lipoproteins play a major role in the cascade of events leading up to
      the manifestations of atherosclerosis as it relates to coronary heart disease
      (CHD). Exercise-induced changes in the blood lipid profile appear to be
      therapeutic, an observation favouring the integration of exercise in CHD
      prevention and treatment programmes. The specific stimuli needed to produce such
      therapeutic effects are yet to be elucidated; both the repeated, transitory
      effects of single, isolated exercise sessions and exercise training effects are
      likely to be involved. The focus of this article is on the acute or short term
      changes of a single session of exercise on plasma lipids and lipoproteins. The
      short term, exercise-induced changes in plasma lipids and lipoproteins are
      reviewed in the context of the role various lipid classifications play in
      coronary artery disease, the many potentially confounding variables that are ever
      present, and the relative effects of gender, exercise modality, and exercise
      intensity. It is concluded that a single bout of exercise has the potential to
      induce short term, transient increases in the high density lipoproteins HDL and
      HDL2 and decreases in triglycerides in men. For women, more research is needed to
      determine clearly the exercise induced short term changes in plasma lipids and
      lipoproteins. It appears that duration and intensity of exercise are directly
      related to the degree of changes observed: bouts of prolonged, intense exercise
      of sufficient energy expenditure appear to induce decreases in triglycerides and
      increases in HDL, primarily through HDL2, of greater magnitude and duration.
      Exercise induced changes in the plasma lipid profile appear to have returned to
      pre-exercise levels by 48 hours postexercise. Recognising that the underlying
      physiological mechanisms for changes in lipids and lipoproteins remain
      inconclusive, the roles of the lipid-regulatory enzymes lipoprotein lipase,
      lecithin: cholesterol acyltransferase, and hepatic triglyceride lipase are
      discussed. It is clear that well controlled studies are needed to examine the
      effects of exercise on short term changes in the blood lipid profile in women.

PMID- 8303147
TI  - Partners in validation.

PMID- 8303146
TI  - Learning contracts in education.

PMID- 8303148
TI  - A maturing profession.

PMID- 8303149
TI  - The higher award--assessing at the differing levels.

PMID- 8303150
TI  - Student nurse learning styles.

PMID- 8303151
TI  - User-led case management.

PMID- 8303152
TI  - Reflective practice for practise.

PMID- 8303153
TI  - Supporting staff facing job loss.

PMID- 8303154
TI  - Perspectives and policy on mental illness.

PMID- 8303155
TI  - Developing a research and development strategy.

PMID- 8303156
TI  - [Immunology of multiple sclerosis. Recent data and therapeutic perspectives].
AB  - Numerous immune abnormalities have been described in multiple sclerosis,
      including dysfunction of humoral, cellular and non specific immunity. The main
      abnormality probably concerns suppressive T cell function. The decrease of this
      function could explain the breakdown of immunological tolerance towards myelin
      antigens. The primary responsibility of these abnormalities in the triggering of
      the disease has still to be demonstrated. Moreover, the antigenic target of
      immune dysfunction has not yet been determined. A better understanding of T cell
      traffic into the central nervous system and of the mechanisms of interactions
      between the T cells and the antigen on one hand, the T cells and the cells
      presenting antigen on the other hand, offer encouraging therapeutic
      possibilities.

PMID- 8303157
TI  - [Treatment of immune deficient neuropathies with intravenous polyvalent
      immunoglobulins. An open study of 16 cases].
AB  - Between June 1989 and February 1992, in an open controlled study 16 patients with
      various types of polyneuropathy were treated with high-dose intravenous
      immunoglobulins (IgIV). Every month during 3 months, each patient received three
      courses of IgIV in doses of 0.4 g/kg/day during 5 successive days. The trial was
      discontinued in case of no response or if the neuropathy was considered as being
      in remission. In the other cases, at most one course of IgIV was given once a
      month if there was significant improvement (assessed by previously published
      clinical functional scales, electrophysiological examinations and titers of
      specific antibodies), or spaced at intervals which varied according to each
      patient, and sometimes in low doses. RESULTS: 1) A first group of 6 patients had
      chronic demyelinating polyneuropathy with severe motor disability. The first
      infusions of IgIV resulted, in 4/6 cases, in a dramatic improvement which lasted
      under regularly spaced courses in lower doses. 2) Four patients had chronic
      neuropathy associated with monoclonal IgM gammopathy of undetermined significance
      (3 had anti-MAG and anti-SPG antibodies, and 1 had anti-GD1a and GD1b antibodies)
      and had not been improved by the usual immunosuppressive treatments. In 1 case
      the IgIV treatment had to be discontinued because of skin allergy. In the
      remaining 3 patients the clinical disorders (mainly the sensory ones) were
      reduced, but no significant improvement of neurophysiological or immunological
      data was observed. 3) Three patients had a purely multifocal motor neuropathy
      with persistent conduction blocks at EMG and high titers of anti-GM1 antibodies
      in 2/3 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8303158
TI  - [Treatment of Wilson's disease with zinc. 5 cases].
AB  - Zinc treatment of Wilson's disease was introduced by Schouwink en 1961 and is
      still uncommon in France. We evaluated the effectiveness and safety of zinc in 5
      patients with Wilson's disease aged from 19 to 40 years. There were three
      neurological, one hepatic and one asymptomatic cases. Zinc was administered in
      doses of 120 to 272 mg/day, alone in 3 cases and combined with D-penicillamine in
      2 cases. After 1 to 7 years of zinc therapy, our experience is consistent with
      data from recent literature and provides further evidence of zinc effectiveness.
      Zinc may be prescribed as first treatment in most patients, including
      asymptomatic cases. The only exception concerns patients with severe symptoms in
      whom it is recommended to combine zinc with D-penicillamine during the early
      phase of treatment for more rapid effectiveness. Because of its safety, zinc is
      particularly indicated in cases of intolerance to D-penicillamine and trien.

PMID- 8303159
TI  - [Transient involuntary movement disorders and thalamic infarction].
AB  - Stroke-related nonepileptic transient dyskinesias are rare, and the site of
      ischemia remains often undetermined. Five cases out of 47 consecutive thalamic
      infarcts (10.6 per cent) are reported. Patients presented with monochorea (1
      case), hemiballism-hemichorea (2 cases), choreoathetosis (1 case with subsequent
      arm painful dystonia and hand tremor), and asterixis (1 case). Magnetic resonance
      imaging demonstrated that the subthalamic nucleus was spared in all cases.
      Transient dyskinesias occurred at any time in the course of infarction (as a
      warning sign in 1 case, as an associated symptom in 3 cases, or during recovery
      in 1 case). Moreover, this study suggests that: 1) transient dyskinesias are
      mainly related to thalamic ischemic injury, and 2) small vessels disease is the
      main etiology.

PMID- 8303160
TI  - [Cerebral hemorrhage in migraine].
AB  - We report a case of intracerebral hemorrhage which occurred during a migraine in
      a 62 year-old woman who had migraine since the age of 20. The patient was
      normotensive. The angiograms were normal. Cerebral hemorrhage in migraine appears
      to be very rare: we found 6 reported cases that were compared with our own. The
      hypothesis of recirculation in an infarcted tissue and the possible role of
      dissecting aneurysms are examined.

PMID- 8303161
TI  - [Multiple mononeuritis and cerebral meningo-arteritis. Wegener disease or Lyme
      disease?].
AB  - The pathogenic mechanisms underlying Lyme disease remain uncertain but an
      increasing number of reports suggest a vascular inflammatory process. On the
      other hand, the so-called systemic vasculitides, even though they remain of
      pathological definition, have recently been characterized by the presence, in the
      serum, of anti-neutrophil cytoplasmic antibodies (ANCA). We report on a patient,
      finally diagnosed as having neuroborreliosis, who presented initially with
      multiple mononeuropathy, ANCA, vascular lesions at muscle biopsy and lymphocytic
      meningitis. Despite antibiotherapy, he presented with two recurrent strokes, from
      which he completely recovered. He also developed oto-sinusitis. The disease was
      finally clinically and biologically controlled by immunosuppressive therapy. The
      relationship between angiitis and Lyme disease are discussed. It is hypothesized
      that Borrelia burgdorferi infection may cause a systemic vasculitis following its
      own course and requiring its own treatment.

PMID- 8303163
TI  - [Thrombosis of the ending internal carotid artery complicating giant aneurysm].
AB  - A 30-year old man suddenly developed left hemiplegia. CT scan and cerebral
      angiography showed complete thrombosis of a right internal carotid giant
      aneurysm. Anterograde propagation of the thrombus in the parent artery led to
      ipsilateral hemispheric infarction, an exceptional presenting symptom of such
      vascular malformation. The diagnostic and etiopathogenic aspects are briefly
      discussed.

PMID- 8303162
TI  - [Partial epilepsy and corpus callosum involvement].
AB  - We report two cases of partial complex epilepsy associated with a lesion of the
      corpus callosum: a cavernoma in one case and a lesion of undetermined nature in
      the other. Similar cases have already been reported, notably with lipomas or
      agenesis of the corpus callosum, but they remain exceptional. Two mechanisms
      could explain such epilepsies: either the lesion extends to the cingulate gyrus
      whence the epileptic discharge may reach internal temporal structures (our case
      n. 1), or a temporal focus becomes autonomic after interruption of inhibitory
      callosal fibres (our case n. 2).

PMID- 8303164
TI  - [Hemiballismus disclosing cerebral toxoplasmosis and acquired immunodeficiency
      syndrome].
AB  - A 33-year-old Saudi woman presented with right hemiballismus of recent onset.
      Brain CT showed a left thalamo-subthalamic lesion which was thought initially to
      be a metastasis or a tuberculoma. The presence of severe subacute diarrhea,
      multiple lymphadenopathies and lymphopenia suggested an acquired immunodeficiency
      syndrome (AIDS). Tests for HIV-1 infection were positive and, despite the absence
      of antitoxoplasma antibodies in the serum, antitoxoplasmic treatment by
      pyrimethamine and sulfadiazine was given. One and a half month later, both
      abnormal movements and CT images had disappeared. The probable source of HIV
      infection was imported packed red blood cells received by the patient 5 years
      earlier. Toxoplasmic brain abscess associated with AIDS should be considered as a
      possible cause of hemiballismus in young adult even in the regions where AIDS is
      still infrequent.

PMID- 8303165
TI  - [Hemianopsia with preservation of temporal crescent and occipital infarction].
AB  - A 34-year-old man experienced a left homonymous hemianopsia due to an occipital
      infarction, with preservation of the temporal crescent on Goldmann perimetry. The
      cortical representation of the temporal crescent is discussed with regard to the
      location of the lesion imaged by magnetic resonance.

PMID- 8303166
TI  - [Isaacs syndrome: clinical remission after methylprednisolone bolus].

PMID- 8303167
TI  - [Meningoradiculitis disclosing T-lymphocyte leukemia in HTLV-1 infection].
AB  - A case of HILV1-associated adult T cell leukaemia/lymphoma (ATLL) in a 21-year
      olf African woman is reported. The patient presented with lymphomatous
      meningoradiculopathy. The usual clinical features of ATLL were absent. Lumbar MRI
      showed a pial enhancement by DTPA-gadolinium of the conus medullaris which
      extended to the proximal cauda equina. Under systemic chemotherapy coupled with
      intrathecal chemotherapy the patient progressively improved, and at the second
      MRI examination complete disappearance of the lumbar enhancement was observed.
      MRI of the brain using axial and coronal T2-weighted sequences detected
      multifocal lesions of high-intensity signal in the subcortical white matter. ATLL
      is unusual in people of African origin. The ATLL-strongyloides infestation
      association has previously been reported, suggesting that parasitic infestation
      may be an important co-factor leading to the development of ATLL.

PMID- 8303168
TI  - Acute care decisions. Ethics in action.

PMID- 8303169
TI  - No more bed baths.

PMID- 8303170
TI  - HIV vaccines--a report from the front.

PMID- 8303171
TI  - New drug bulletins: loratadine (Clarium); rimantadine (Flumadine).

PMID- 8303172
TI  - Can you spot an alcoholic patient?

PMID- 8303173
TI  - Emergency cardiac care. A quick response to life-threatening arrhythmias.

PMID- 8303174
TI  - The law adds force to your voice.

PMID- 8303175
TI  - Listen to what patients don't say.

PMID- 8303176
TI  - [Practical value of the histopathological diagnosis of malignant lymphomas].
AB  - The term malignant lymphoma (ML) covers several lymphoid tumoral diseases of
      varying aggressiveness. Nowadays, histopathology makes it possible to
      individualize entities corresponding to cellular types well defined by their
      cytology, their selective invasion of certain lymph node compartments, their
      immunophenotype and sometimes their cytogenetic and molecular markers. Some of
      these entities are not yet known to non-specialists. Mantle cell-derived
      malignant lymphoma, monocytoid B-cell lymphoma, low-grade MALT type malignant
      lymphoma, large mediastinal cell malignant lymphoma and large anaplastic cell
      malignant lymphoma are examples of these entities, each of them having its own
      clinical manifestations.

PMID- 8303177
TI  - [How to progress in the histopathological classification of malignant non
      Hodgkin's lymphomas].
AB  - Classifications of malignant lymphomas (ML) are aimed at separating different
      morphological entities that can be recognized by histopathologists and anatomico
      clinical entities that are useful to clinicians. With these classifications,
      entities with different proliferative and disseminating potential can be
      distinguished, and the effects of treatment on the various types of ML can be
      compared. The advances expected in the near future will be due to techniques
      which are already known and will provide information on the proliferative power
      of lymphoma cells, on the significance of chromosomal abnormalities, on
      hyperexpression of certain cytokines or expression of certain adhesion molecules,
      and on the role played by the presence of the genome of some viruses in tumoral
      cells. Yet the most important advances in this field will perhaps be due to
      hitherto unknown techniques or to not yet imaginable new research lines.

PMID- 8303178
TI  - [Histogenesis of malignant lymphomas].
AB  - The strides achieved by immunohistochemical techniques, the development of
      monoclonal antibodies and, more recently, molecular biology have brought deep
      changes in the concept of histogenesis and in the classification of malignant
      lymphomas. After blockage, each of the cells which mark out the transformation of
      B and T may give birth to a malignant lymphoma. In most cases
      lymphoproliferations retain the immunological (differentiation markers) and
      morphological attributes of the normal cells from which they derive. It is on
      this corpus of data that the present histogenesis and classifications are
      resting. However, the complexity of lymphoma histogenesis is related to
      heterogeneous lymphoid populations which are not a mere division into B and T
      cells. There are numerous and not yet clearly individualized subpopulations the
      morphological and antigenic features of which are imperfectly known. On the other
      hand, the development of in situ hybridization techniques and of molecular
      biology (PCR) has provided useful data on the aetiology of malignant lymphomas.
      The latest results obtained suggest that several viruses (Epstein-Barr, HTLV-1,
      HHV-6) might play a predominant oncogenic role.

PMID- 8303179
TI  - [Sites of lymphomas].
AB  - Non-Hodgkin's lymphomas are malignant tumours of lymphotic tissue. They
      predominantly involve the lymph nodes but may affect all organs. The distribution
      of lymphomas is summarized in the Ann Arbor classification into two types of
      extranodal tumours: localized primary lymphomas and secondary lymphomas
      expressing a disseminated disease. The most frequent sites of secondary lymphomas
      are the bone marrow and the liver, while those of primary lymphomas are the
      digestive tract and the E.N.T. region. The diagnosis is complicated by the
      clinical polymorphism of extranodal lymphomas, particularly when the tumour is
      located in regions such as the brain, where histological samples are difficult to
      obtain. The prognosis does not rest on the multiplicity of clinical presentations
      but exclusively on the histology and size of the tumoral mass. Only
      cerebromeningeal and cutaneous lymphomas require special treatments.

PMID- 8303180
TI  - [Prognostic factors in non-Hodgkin's lymphomas. Therapeutic implications].
AB  - This review considers the prognostic factors recently distinguished in malignant
      lymphomas. Whatever the histological type, clinical and biological factors have a
      major role in defining the forms having poor prognosis. These prognostic factors
      are essentially linked to the tumoral mass (stage, number of metastases, and LDH
      and beta-2-microglobulin levels). Age is also an important factor. When treatment
      of lymphoma is considered, whatever the histological type, the presence or
      absence of these prognostic factors must be taken into account in choosing
      treatment.

PMID- 8303181
TI  - [Follicular lymphomas].
AB  - Follicular lymphomas are a subgroup of non-Hodgkin's lymphomas with a low-grade
      malignancy. They are characterized by a frequent chromosome abnormality, a
      translocation between chromosome 14 and chromosome 18. This translocation plays a
      role in the development of this disease. The course of follicular lymphomas is
      slow, usually lasting several years but is ultimately fatal, Their treatment is
      controversial. Recently, an association of chemotherapy and alpha interferon
      appeared promising. Other drugs such as fludarabine or 2' chlorodeoxyadenosine
      are currently tested.

PMID- 8303182
TI  - [Aggressive lymphomas].
AB  - The term "aggressive lymphoma" applies to the intermediate severity and high
      malignancy lymphomas of the international classifications. Despite their
      heterogeneity, the lymphomas of this group should be cured by modern treatments.
      The therapeutic approach depends on the presence or absence of adverse prognostic
      factors. When these factors are absent cure can be obtained in 80 to 90% of the
      cases by chemotherapy or chemo-radiotherapy. The basic treatment rests on
      chemotherapy adjusted to the severity of the disease. In its least severe forms
      the different chemotherapeutic combinations available have about the same
      effectiveness, and it is rational to choose the least toxic of them. Intensive
      treatments are reserved to patients with several factors of poor prognosis. In
      such cases, complete remission rates may be close to 65%, but the percentage of
      long-term survival is only 40%, and new therapeutic approaches are required. At
      present, in addition to intensified conventional therapy made possible by growth 
      factors, the possibility or early intensification with haematopoietic stem cells
      autografts is being studied. Intensive treatments can only be given to young
      subjects. Lymphoblastic and Burkitt's must be approached differently when
      medullary or meningeal tissues are invaded.

PMID- 8303183
TI  - [Low-grade mucosa-associated lymphoid tissue (MALT) lymphomas].
AB  - Lymphomas of mucosa-associated lymphoid tissues (MALT) are localized in organs
      containing lymphoid tissue in normal subjects (lung) or in organs frequently
      involved by inflammatory lesions (stomach, salivary glands, thyroid...). In the
      MALT, lymphoid tissue comprises B and T lymphocytes. Lymphomas of the MALT have
      been well defined in the gut. Isaacson has proposed a classification of these
      primary gut lymphomas, distinguishing between B, the most frequent, and T
      lymphomas, and between low and high grade of malignancy. MALT lymphomas have
      common morphological characteristics and a particular behaviour: they are
      localized in their initial site for a long time. Prognostic factors include low
      histological grade of malignancy and the possibility of a complete surgical
      resection.

PMID- 8303184
TI  - [Lymphomas in immunocompromised hosts].
AB  - Congenital and acquired states of immunodeficiency are associated with an
      increased incidence of ill-defined lymphoproliferations. These are mainly B-cell,
      often extranodal, lymphoproliferations commonly associated with EBV. Their
      incidence is increasing with the rapid development of organ transplantation and
      spreading of the HIV infection. The association with EBV partly explains the
      pathogeny of these affections. This ubiquitous virus immortalizes B lymphocytes
      in vitro and is tumorigenic for new world primates. An EBV-specific cytotoxic T
      cell memory prevents uncontrolled proliferation of infected B cells in normal
      subjects after the primary infection. The X-linked lymphoproliferative syndrome
      is a primary immunodeficiency characterized by an abnormal immune responsiveness
      to EBV, resulting in fatal infectious mononucleosis and malignant lymphoma. The
      severe immunosuppression present in transplanted patients allows EBV infected
      cells to proliferate, giving rise to a spectrum of lymphoproliferations.
      Reduction of immunosuppression alone is, in some cases, sufficient to produce
      tumor regression. The evolution of these affections is difficult to predict and
      requires a combined biological and clinical analysis, in order to evaluate the
      aggressivity of the tumor and the ability of the immune response of the host. HIV
      infected patients have an increased risk of developing Burkitt's lymphomas which
      are associated with EBV in 50% of the cases. Patients with AIDS at an advanced
      stage, present immunoblastic large cell lymphomas associated with EBV, similar to
      the post-transplant lymphomas. Lymphoproliferations in immunodeficiencies
      constitute a model for evaluation of the interaction between EBV and the immune
      system.

PMID- 8303185
TI  - [Non-Hodgkin's lymphomas in children].
AB  - In children, lymphomas are highly malignant and belong to the Burkitt type (B
      cells) or to the non-Burkitt lymphoblastic type (T-cells). Most of the lesions
      are abdominal (gastrointestinal tract, mesentery) and/or mediastinal. The disease
      is often diagnosed on the cytology of an effusion or on a bone marrow
      differential cell count, and if these are negative, on a biopsy of the tumoral
      mass. The patients must be taken care of immediately, in conditions of emergency
      and in a way appropriate to the situation (renal function, prevention or
      treatment of lysis syndrome). Treatment consists of chemotherapy adjusted to the
      histo-immunological type. It currently cures 80% of the children.

PMID- 8303186
TI  - [Treatment of recurrent lymphoma].
AB  - Patients with recurrent lymphoma have a poor prognosis, even when a new remission
      can be obtained. In follicular lymphomas this remission is shorter. In aggressive
      lymphomas less than 10% of the patients survive for 5 years. Salvage treatments
      include drugs that were not administered in the induction of treatment. In
      follicular lymphomas new drugs which interfere with adenosine deaminase are very
      promising. In view of the bad results of rescue treatment and of the good
      sensitivity of lymphomas, even when recurrent, to radiotherapy and chemotherapy,
      intensive treatments combined with allogeneic or autologous graft of
      haematopoietic stem cells have been tested, and the results obtained seem to be
      better than those of conventional treatments. The position of these new
      treatments will be more clearly defined when the results of randomized studies
      are known. However, the prognosis of recurrent lymphoma can be further improved
      by reducing the toxicity of intensive treatments with the use of haematopoietic
      growth factors, by ridding the graft of malignant cells and by stimulating the
      post-graft immune defence to diminish the incidence of recurrences.

PMID- 8303187
TI  - [Surveillance of patients treated for lymphoma].
AB  - The treatment of malignant non-Hodgkin's lymphoma rests on chemotherapy, and the
      main purpose of monitoring is to detect and prevent the side-effects of
      chemotherapy, to ensure that it is administered according to the rules set up in
      the therapeutic protocol and, of course, to check on its effectiveness. Later on,
      the future of the patient will be threatened by the risk of recurring lymphoma
      and by the late side-effects of the therapeutic drugs.

PMID- 8303188
TI  - [Arthroscopy of the shoulder. A diagnostic and therapeutic procedure].

PMID- 8303189
TI  - [Peridural anesthesia and anticoagulants. A difficult marriage of convenience].

PMID- 8303190
TI  - [Treatment of Crohn disease].

PMID- 8303191
TI  - [Medical secret and occupational medicine. The history and texts].

PMID- 8303192
TI  - [Atherosclerosis. Pathological anatomy].

PMID- 8303194
TI  - [Tumors of the bladder. Pathological anatomy].

PMID- 8303193
TI  - [Myocardial infarction. Pathological anatomy].

PMID- 8303195
TI  - [Cancer of the prostate. Pathological anatomy].

PMID- 8303196
TI  - [Cancer of the testis. Pathological anatomy].

PMID- 8303197
TI  - [Kidney cancer in adults. Pathological anatomy].

PMID- 8303198
TI  - [Cancer of the uterine cervix. Pathological anatomy].

PMID- 8303199
TI  - [Tumors of the breast. Pathological anatomy].

PMID- 8303201
TI  - [Epithelial cutaneous cancers. Pathological anatomy].

PMID- 8303200
TI  - [Tumors of the ovarian epithelium. Pathological anatomy].

PMID- 8303202
TI  - [Malignant melanoma. Pathological anatomy].

PMID- 8303203
TI  - Mucosal origin and shedding of an early colonic tumor marker defined by Adnab-9
      monoclonal antibody.
AB  - Recent attention has been drawn to the diagnostic potential of tests based on
      shed colonic tumor markers. Adnab-9 monoclonal antibody raised against
      neoplastic, potentially premalignant colonic adenomas recognizes a marker in
      colonic effluent or tissue which correlates with the presence of tumors or risk
      of colorectal cancer. The origin of this antigen and optimal collection of
      colonic effluent were investigated by enzyme-linked immunosorbent assay and
      Western blotting. Mean Adnab-9 binding in effluent samples from colorectal cancer
      patients even after resection is high as compared with that in normal subjects (P
      < 0.05). Effluent samples are best collected in the morning hours. Antigen
      proteolysis may be significant depending on the site and timing of effluent
      collection, but breakdown products are reactive. Tissue and effluent Adnab-9
      binding at any one anatomic site of collection appear to correlate (r = 0.88, P =
      0.01). The Adnab-9 antigen is constitutively expressed at low levels throughout
      the distal bowel and localized to the deepest regions of the mucosal crypts.
      Other than meconium, no significant levels of binding are found in other body
      fluids. This antigen is specific for the gastrointestinal tract, its binding in
      conveniently collected effluent samples correlates with tissue content, and the
      antigen is constitutively expressed in the crypts of the distal small bowel and
      colonic mucosa.

PMID- 8303204
TI  - Inflammation as a major cause of fluid losses in small-bowel obstruction.
AB  - The importance of inflammation for fluid losses in obstructive ileus was
      investigated in vivo in the rat. Inflammation was quantified by spectrophotometry
      of extravasated Evans blue (Eb)-albumin. Net fluid secretion in the obstructed
      jejunum was measured by a continuous gravimetric technique. The inflammation in
      the obstructed gut wall was significantly more pronounced than that in the gut
      distal to the obstruction and the sham-obstructed gut. The inflammation was
      significantly more pronounced in the serosa and external muscle layer than in the
      mucosa-submucosa. Acid-base balance in obstructed animals showed a significant
      metabolic alkalosis, whereas serum albumin and electrolytes were normal. Lumen
      fluid in obstructed animals showed low levels of albumin and total calcium as
      compared with serum, whereas fluid from the peritoneal cavity of obstructed rats
      showed high contents of albumin. Indomethacin and hydrocortisone given
      intravenously to obstructed animals significantly reduced the degree of
      extravasated Eb-albumin in the obstructed gut wall. Sham-operated animals showed
      net fluid absorption, whereas obstructed rats showed net fluid secretion.
      Secretion in obstructed animals was in all cases reversed into net fluid
      absorption after intravenous administration of indomethacin and hydrocortisone.
      These findings suggest that a pronounced inflammation occurs in the wall of the
      obstructed small intestine and that this inflammation plays an important role in
      the pathogenesis of the profuse fluid losses of obstructive ileus.

PMID- 8303205
TI  - Portal hypertension and esophageal varices in cystic fibrosis. Unreliability of
      echo-Doppler flowmetry.
AB  - To investigate the role of echo-Doppler flowmetry in evaluating patients with
      cystic fibrosis and portal hypertension at risk of esophageal varices, we studied
      26 subjects divided in 3 groups: 9 with portal hypertension and esophageal
      varices, 8 with chronic liver disease without varices, and 9 without chronic
      liver disease. Spleen size, diameter, blood velocity, and flow rate of portal,
      splenic, and superior mesenteric veins were recorded. In patients without chronic
      liver disease Doppler measurements were repeated on 2 different days to assess
      intraobserver variability. Significant differences among the three groups were
      found for mean values of spleen size and diameters of portal, splenic, and
      superior mesenteric veins. Nevertheless, a considerable overlapping of individual
      data was observed. No differences were observed in mean hemodynamic measurements,
      except for blood velocity in portal vein and flow rate in splenic vein. The
      intraobserver variability for repeated Doppler measurements was clinically
      unacceptable for most of the variables studied. Echo-Doppler assessment of
      splanchnic flow seems to be an unreliable tool in the management of cystic
      fibrosis patients with portal hypertension at risk of esophageal varices.

PMID- 8303206
TI  - Effect of wheat fibre supplements on duodenal ulcer recurrence.
AB  - In the present study the prophylactic effect of concentrated wheat fibre on
      duodenal ulcer recurrence was evaluated. Eleven grams of fibre (Fiberform) or
      placebo was added to an ordinary Norwegian diet for 1 year after endoscopic
      healing of duodenal ulcer. The ulcer recurrence rates were 84% (31 of 37
      patients) in the fibre-supplemented group and 85% (30 of 36 patients) in the
      placebo group (NS). The effect on ulcer symptoms was similar in both groups. Side
      effects were infrequently seen. A concentrated wheat fibre supplement seems to
      have no preventive effect when given to duodenal ulcer patients living on a
      traditional Norwegian diet.

PMID- 8303207
TI  - Evaluation of acetic acid-induced gastric ulcers in dogs by endoscopic
      ultrasonography.
AB  - To clarify the ability of endoscopic ultrasonography (EUS) to diagnose gastric
      ulcer, we induced gastric ulcer (19 open ulcers and 11 ulcer scars) by injecting
      acetic acid into the stomach via an endoscope in 15 dogs. The stomachs were
      resected and scanned by EUS in a water bath, and the findings were compared with
      the histologic observations. The ulcer depth was correctly diagnosed in 29 of 30
      instances (96.7%). In active, open ulcers the width and depth of the ulcer crater
      and the thickness of the gastric wall around the crater measured in the
      photographs obtained by EUS corresponded with those observed in histologic
      photographs. In the ulcers disrupting the muscularis propria layer the distance
      between the disrupted muscularis propria layer in EUS also corresponded to the
      histologic observations. In all ulcer lesions the low-echoic area below the ulcer
      in EUS corresponded to the histologic area of granulation or fibrosis. However,
      it was difficult to distinguish granulation from fibrosis by EUS. EUS is thus
      considered useful for evaluating gastric ulcers quantitatively in the clinical
      setting.

PMID- 8303208
TI  - Diagnosis and treatment of acute lower gastrointestinal bleeding.
AB  - Diagnostic sigmoidoscopy and barium enema examinations (n = 214) or colonoscopy
      (n = 52) were performed for acute lower gastrointestinal (GI) bleeding. The cause
      of bleeding was detected in 76% (203 of 266) of the primary examinations, and the
      cause remained unclear after subsequent examinations in 17% of the cases.
      Hemorrhoids were the cause of bleeding in 28% (56 of 203) of the cases, colonic
      diverticular disease in 19% (39 of 203), adenomatous polyps in 11% (23 of 203),
      and colorectal cancer in 10% (20 of 203). The sources of bleeding did not differ
      significantly by sex. An anorectal site of bleeding was most often detected in
      patients less than 50 years of age (p < 0.0001) and a left colonic site in those
      more than 70 years (p < 0.0001). Hemorrhoids significantly more often caused
      rectal bleeding among the youngest patients (p < 0.0001) and colonic diverticular
      disease among the oldest patients (p < 0.0001) and colonic diverticular disease
      among the oldest patients (p < 0.0001) than among the others. Of the 266
      patients, 19% have been operated on for the bleeding lesion. The mortality
      related to lower GI bleeding was 4% (11 of 266). The mean age of the patients who
      died was higher than that of those who survived (p < 0.05).

PMID- 8303209
TI  - Helicobacter pylori infection in a randomly selected population, healthy
      volunteers, and patients with gastric ulcer and gastric adenocarcinoma. A
      seroprevalence study in Taiwan.
AB  - To investigate the association of Helicobacter pylori and gastric ulcer and
      adenocarcinoma, IgG antibodies against H. pylori were examined in 823 randomly
      selected subjects, 92 healthy volunteers, 117 patients with gastric ulcer, and
      148 with gastric adenocarcinomas in Taiwan, where the prevalence of gastric
      adenocarcinoma is high. The seropositivity of this population in Taiwan was
      54.4%. Gastric ulcer patients had a higher seropositivity (83.8%) than healthy
      volunteers (62.0%) and gastric adenocarcinoma patients (62.2%) (P < 0.001).
      Gender difference, blood type, and habit of smoking were not associated with the
      seroprevalence in any study groups. Gastric ulcer coexistent with duodenal ulcer
      had a higher seropositivity (94.7%) (P < 0.05). The seropositivity of H. pylori
      in gastric adenocarcinoma patients was higher than in healthy volunteers only in
      younger age and was not associated with histologic type, invasion, and location
      of major tumors. The results reemphasize the association of H. pylori infection
      with gastric ulcer but not with gastric adenocarcinoma in Taiwan.

PMID- 8303210
TI  - Faecal calprotectin: a novel test for the diagnosis of colorectal cancer?
AB  - Calprotectin, a prominent cytosol protein in neutrophil granulocytes, was present
      in increased concentrations in stools from 50 of 53 patients with colorectal
      cancer, 32 of 40 patients with colorectal polyps, and all of 18 patients with
      gastric cancer. After radical surgery, faecal calprotectin levels reverted to the
      normal range in all but one patient with colorectal cancer. Calprotectin
      determinations are simplified by the stability of this protein in stools.
      Reliable estimates can be obtained in samples of only 5 g. On the basis of data
      from the literature, the test for calprotectin seems better than that for occult
      blood for the detection of gastrointestinal neoplasms.

PMID- 8303211
TI  - A prospective study of first attacks of inflammatory bowel disease and non
      relapsing colitis. Microbiologic findings.
AB  - In 105 patients with a first attack of colitis, thorough microbiologic
      investigations of rectal biopsy, faecal, and serum samples were performed with
      the aims of identifying the colitis-causing agents and shedding light on factors
      that may precipitate or aggravate the onset of inflammatory bowel disease. Sixty
      one patients were found to have inflammatory bowel disease. In 13 (21%) of these
      patients microbial findings were positive. Eight of the 61 patients fell ill
      during or immediately after antibiotic treatment, and 10 while travelling abroad.
      Forty-one of the 105 patients had non-relapsing colitis. In 32 (78%) of these the
      microbial findings were positive. Six of these 41 patients fell ill during or
      immediately after antibiotic treatment, and 14 while travelling abroad.
      Alteration of the intestinal microflora on travelling, gastrointestinal
      infection, or treatment with antibiotics seems to precipitate or aggravate the
      symptoms in latent inflammatory bowel disease. In such patients the mode of onset
      is often changed from insidious to more acute, which may cause difficulty in
      differentiation from non-relapsing colitis.

PMID- 8303212
TI  - Pancreatic atrophy: a new model using serial intra-peritoneal injections of L
      arginine.
AB  - No simple rat model for chronic pancreatitis exists at present. A single dose of
      arginine has recently been shown to induce acute pancreatitis in rats. This study
      was designed to assess whether serial injections of arginine would induce
      reproducible chronic pancreatic damage. Forty rats received an intra-peritoneal
      injection of 500 mg per 100 g body weight of L-arginine followed by three
      injections of 250 mg per 100 g over 10 days. The rats were killed 24 h after each
      injection and at intervals of up to 6 months. Serum amylase levels were increased
      in the acute phase only. Examination of the pancreas at 24 h showed a severe
      oedematous pancreatitis. By day 5 there was up to 90% acinar destruction with
      adipose tissue replacement, although ductal, vascular, and islet cells appeared
      undamaged. These changes were present 6 months after injection. This is proposed
      as a new, simple, and reproducible method of inducing chronic pancreatic damage
      in the rat.

PMID- 8303213
TI  - Effect of stimulation of mucosal HCO3- secretion on acid-induced injury to
      porcine duodenal mucosa.
AB  - The effect of stimulation of duodenal mucosal bicarbonate secretion with
      vasoactive intestinal peptide (VIP) on acid-induced damage to the duodenal mucosa
      was studied in anaesthetized pigs in which bile and pancreatic juice were
      diverted from the duodenum. Mucosal damage was quantitatively assessed
      histologically, and mucosal blood flow was determined by means of radioactively
      labelled microspheres. Compared with placebo, intravenous infusion of VIP (500
      pmol/kg/h) significantly stimulated duodenal mucosal bicarbonate secretion (47 +/
      13 versus 249 +/- 53 mumol/h) without concomitant changes in mucosal blood flow
      (51.5 +/- 7.8 versus 48.5 +/- 9.1 ml/min/100 g) or arterial bicarbonate
      concentration (24.2 +/- 1.1 versus 23.4 +/- 0.9 mM). The same dose of VIP
      increased the acid disappearance rate in the duodenum (2.2 +/- 0.14 versus 3.3 +/
      0.09 mmol/h) and reduced the extent of damage to the duodenal surface (16 +/- 2%
      versus 7 +/- 2%) during duodenal infusion of 0.03 M HCl but not 0.1 M HCl. We
      conclude that the protection offered by VIP against the small dose of acid is
      most likely secondary to the effect of VIP on mucosal bicarbonate secretion.
      Thus, this study suggests that duodenal mucosal bicarbonate secretion,
      independent of mucosal blood flow, is an integral factor in duodenal mucosal
      defence.

PMID- 8303214
TI  - Micronutrient antioxidant status in tropical compared with temperate-zone chronic
      pancreatitis.
AB  - Micronutrient antioxidants interact with glutathione in tissues to facilitate the
      disposal of reactive oxygen species and xenobiotic metabolites derived via
      cytochromes P450. Published evidence linking cytochrome P450I induction with
      chronic pancreatitis therefore led us to compare antioxidant status in patients
      at Manchester in the northwest of England and at Madras in the southeast of
      India. Serum studies in healthy volunteers showed that the biologic
      availabilities of selenium and alpha-tocopherol were equally high in the two
      zones but that the availabilities of beta-carotene and ascorbic acid were lower
      in the tropical area (p < 0.001), where the ratio of ascorbic acid to total
      vitamin C concentration in serum was substantially reduced (p < 0.001). The serum
      antioxidant profiles of the chronic pancreatitis groups reflected these
      indigenous differences: a decrement in selenium and alpha-tocopherol was evident
      in both zones, whereas beta-carotene and ascorbic acid values were subnormal only
      in the Manchester group. The concentration of inorganic sulphate in urine--an
      index of long-term intake of sulphur amino acids for synthesis of glutathione and
      other detoxifiers--was similar in controls and patients from Manchester, but
      levels were lower than in their Madras counterparts (p < 0.02, p < 0.01,
      respectively). The results suggest that culinary practices that erode the
      biologic availabilities of ascorbic acid and beta-carotene may predispose to
      pancreatic oxidative stress and thereby to the changes leading to chronic
      pancreatitis at an early age in south India. These findings have implications for
      treatment and prophylaxis.

PMID- 8303215
TI  - Gastric lesions induced by concentrated ethanol are associated with a decrease in
      gastric calcitonin gene-related peptide-like immunoreactivity in rats.
AB  - Gastric calcitonin gene-related peptide-like immunoreactivity (CGRP-li) was
      decreased in the gastric corpus of rats treated with 75% or 96% ethanol but not
      with 50% ethanol. The extent of gastric lesions was related to the increasing
      concentrations of ethanol (50-96%). CGRP-li decrease was evident already at 5 min
      after the 96% ethanol challenge, whereas a peptide recovery resulted 10 days
      after, concomitant with the healing of gastric lesions. Ethanol (96%) produced a
      significant decrease of CGRP-li in the whole thickness of the gastric corpus but
      not in the mucosal layers of the same area, indicating that the muscular layer of
      the gastric corpus is the zone involved in this phenomenon. Pretreatment with the
      selective sensory neurotoxin capsaicin induced a gastric CGRP-li decrease in the
      corpus and forestomach. Ethanol (96%) did not further decrease gastric corpus
      CGRP-li in capsaicin-pretreated rats. These findings suggest that 96% ethanol
      induced a decrease of CGRP-li deriving from a capsaicin-sensitive pool and that
      CGRP may play a role in gastric ulcer pathogenesis of haemorrhagic lesions
      induced by concentrated ethanol.

PMID- 8303216
TI  - Comparison between radiologic and endoscopic evaluation of the continent
      ileostomy reservoir.
AB  - The present study was performed to compare the results of radiologic examination
      and endoscopy in 156 patients with continent ileostomy reservoirs. Data from
      clinical follow-up and findings at revisional surgery were used for confirmation
      of diagnosis. One hundred and one patients had the clinical diagnosis nonspecific
      inflammation, 48 had symptoms of valve dysfunction, and 7 were studied because of
      suspected valve-shunting fistulas. For moderate and severe inflammation the
      findings on radiographs and at endoscopy were in accordance, whereas slight
      inflammation was more frequently reported by radiology than endoscopy. Radiology
      overdiagnosed slight inflammation. One disadvantage of endoscopy in patients with
      inflammation was that the afferent ileal segment could be reached in only 56%. By
      radiology 41 of 44 defective valves were identified (93%), whereas endoscopy
      disclosed only 24 defective valves (55%). The combined efforts of radiologic
      examination and endoscopy only managed to diagnose three of the seven patients
      with valve-shunting fistulas (two by radiologic and one by endoscopic
      examination). In conclusion, the retrograde double-contrast examination is a
      valuable complement in the assessment of patients with continent ileostomies and
      appears to be superior to endoscopy in the diagnosis of valve dysfunction and in
      depicting the afferent ileal segment.

PMID- 8303217
TI  - Staphylococcus epidermidis--hospital epidemiology and the detection of
      methicillin resistance.
AB  - Infections in immunocompromised patients and in patients with indwelling
      prosthetic devices are often caused by hospital strains of Staphylococcus
      epidermidis resistant to methicillin. Tests for the detection of methicillin
      resistance, indicating resistance to all beta-lactam antibiotics, were evaluated
      in order to define a suitable screening test. A broth tube breakpoint test with a
      large inoculum, 10(7) colony forming units (cfu), gave the highest recovery of
      resistant strains. False resistance due to hyperproduction of beta-lactamase was
      excluded. The results correlated completely with the detection of the resistance
      gene, mecA, by the polymerase chain reaction. In 2/3 of the resistant strains
      tested the expression of the methicillin resistance was heterogeneous, only one
      cell in 10(2) to 10(4) expressed the resistance within 72 h in both. In broth
      screening tests an inoculum of at least 10(6) cfu therefore was required to
      detect all resistant strains within 24 h. Using agar dilution, 48 h incubation
      must be considered. In disc diffusion tests reliable results were obtained after
      only 16 h of incubation when discs containing cephradine 5 and 30 micrograms,
      oxacillin 1 microgram or cephalexin 30 micrograms were used, and the first disc
      is recommended for routine work. The epidemiology of S. epidermidis strains
      resistant to ciprofloxacin and/or gentamicin was studied in an isolation unit for
      patients undergoing bone marrow transplantation. Antibiograms and plasmids were
      used for typing and 31 such strains were found. Of 54 staff members 10 were
      colonized in the nares only, two in the nares and perineum and one in the nares
      and stool. In ambient air and on the clothes of staff a few of the strains
      predominated quantitatively. These strains colonized the skin of some of the
      patients who seemed to be the main dispersers. Possible routes of cross-infection
      were indirect contact transfer via the hands and clothes of staff (82% of the
      clothes were contaminated), and direct as well as indirect airborne transmission.
      To study the effects of chlorhexidine on skin bacteria, ten nurses washed one arm
      with chlorhexidine-detergent every morning for 3 weeks; the other arm served as
      control. The depression of the normal skin flora did not lead to a colonization
      with more antibiotic-resistant hospital strains. During the wash period the
      counts of antibiotic-resistant S. epidermidis on the treated arms were
      significantly reduced compared with the control arms, as also were the number of
      different strains.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8303218
TI  - The manifestations of schizophrenia in late life: a dearth of data.
AB  - Published data about the course of schizophrenia in late life are very limited.
      Overall, elderly patients with schizophrenia appear to suffer less from active or
      positive symptoms and more from residual or negative symptoms than they did when
      they were younger; therefore, older patients usually require a different type of
      management. There exists strong evidence that deterioration in schizophrenia
      generally occurs earlier rather than later in the disorder's natural history and
      is typically not relentlessly progressive. Nonetheless, schizophrenia remains a
      severe disorder that can be chronic and, in a proportion of patients, unremitting
      throughout life. Few studies have outlined which factors are associated with a
      more positive outcome.

PMID- 8303219
TI  - Late-life schizophrenia: editor's introduction.
AB  - Until recently, most of the research on schizophrenia has focused on young
      adults. With increasing longevity, the number of older schizophrenia patients in
      the population is expected to grow. Late-life schizophrenia patients fall into
      two groups: those who developed schizophrenia for the first time in later
      adulthood (late-onset schizophrenia) and those who developed the illness earlier
      in life and are presently middle-aged or elderly. There is a scarcity of
      published studies on late-life schizophrenia. The available data tend to
      challenge the commonly held view of schizophrenia as a disorder with onset
      restricted to the first half of life and a progressively deteriorating course.
      Further work on this important but long-neglected patient population is urgently
      needed for clinical as well as research purposes.

PMID- 8303220
TI  - The epidemiology of late-onset schizophrenia.
AB  - We report an analysis of a large catchment area sample of patients with
      nonaffective functional psychoses presenting across all ages at onset. The
      male:female ratio was 1.56:1 in the 16-25-year age group; it reached unity around
      30 years of age and declined to 0.38:1 in the 66-75-year group. Contrary to
      expectation, a higher proportion of patients with onset of illness after 45 years
      than of younger onset patients fulfilled DSM-III-R criteria for schizophrenia
      (52% vs. 38%). The distribution by age at onset was much the same irrespective of
      stringency of diagnosis. The highest rates were in the 16-25-year age group, with
      a slight second peak in the 46-55-year group, and a third (more emphatic) peak in
      the over-65 group. A closer analysis of demographic and phenomenologic variables
      revealed distinct differences between patients with early and late (after 44
      years) onset of illness.

PMID- 8303221
TI  - Clinical characteristics of late-onset schizophrenia and delusional disorder.
AB  - We compared 20 patients with late-onset schizophrenia, 7 with delusional disorder
      with hallucinations (paraphrenia), and 13 with delusional disorder without
      hallucinations (late-onset paranoia). We found that these three categories could
      be distinguished from each other on some clinical parameters. Late-onset
      schizophrenia was characterized by bizarre delusions; auditory hallucinations; to
      a lesser degree, first-rank and negative symptoms; and premorbid personality of
      the paranoid or schizoid type. Paraphrenia was associated with predominantly
      nonbizarre delusions, auditory hallucinations, earlier onset of symptoms, and
      paranoid or schizoid personality. Paranoia (late-onset) was characterized by late
      onset of symptoms, nonbizarre delusions, relatively intact premorbid personality,
      and an underlying physical stratum.

PMID- 8303222
TI  - Schizophrenia in late life: elderly patients admitted to an acute care
      psychiatric hospital.
AB  - Although a considerable body of biological and clinical data has been accumulated
      on the mood disorders and organic disorders of late life, only a handful of
      studies have focused on aging schizophrenia patients. Using the results of a
      comprehensive evaluation of all elderly patients admitted over a 30-month period
      to a 26-bed acute care geriatric unit, we compared the demographic, social, and
      clinical characteristics of schizophrenia patients, patients with recurrent major
      depression with and without psychotic features, and patients with primary
      degenerative dementia of the Alzheimer's type with and without delusions. The
      main findings of this study are that elderly schizophrenia patients were younger,
      more often African-American, more often single, and poorer than the other groups.
      A concomitant history of substance abuse and institutionalization as an outcome
      were more frequent among schizophrenia patients. Like the older depressed and
      demented patients, schizophrenia patients were predominantly female and commonly
      presented with several medical disorders. The potential significance of these
      findings is discussed in the context of the literature on the long-term outcome
      of schizophrenia.

PMID- 8303223
TI  - Leukotomy and aging in chronic schizophrenia: a followup study 40 years after
      psychosurgery.
AB  - Many followup studies have found that frontal leukotomy does not lead to marked
      changes in behavioral or cognitive functions in patients with chronic
      schizophrenia. However, these studies left open the issue of whether aging
      interacts with frontal lobe lesions in some way. This study examined 24 elderly
      schizophrenia patients who had experienced a bifrontal leukotomy and 48 subjects
      who were similar to the leukotomized patients in age, gender, chronicity, and
      overall severity of cognitive impairment. Clinical ratings of schizophrenic
      symptoms and cognitive deficits were obtained, as was a neuropsychological
      evaluation. Very few cognitive effects of leukotomy were noted, although
      clinically rated deficits in self-care were more severe in the leukotomized
      sample. These findings again suggest that the cognitive effects of frontal
      leukotomy procedures are limited and imply that aging does not interact
      substantially with leukotomy in patients with chronic schizophrenia.

PMID- 8303224
TI  - Sensory gating and inhibitory function in late-life schizophrenia.
AB  - Although similarities between the cognitive deficits observed in schizophrenia
      and those observed in aging have been recognized for over 50 years, little work
      has been done to directly examine these similarities or their implications for
      late-life schizophrenia. We review studies of prepulse inhibition, habituation,
      latent inhibition, and negative priming that indicate marked similarities in the
      patterns of deficits observed in schizophrenia and in aging. We also present new
      data from preliminary studies of prepulse inhibition and negative priming in
      which we compare young normal controls, older adult normal controls, and late
      life schizophrenia patients. For both measures, both schizophrenia patients and
      older adults showed an inhibitory deficit relative to young controls. In the case
      of negative priming, older schizophrenia patients showed evidence of greater
      inhibitory dysfunction than did normal older adults, suggesting that older
      schizophrenia patients suffer a deficit resulting from the combined effects of
      schizophrenia and aging. The implications of these results and directions for
      future research are discussed.

PMID- 8303225
TI  - Sensory impairment in late-life schizophrenia.
AB  - We reviewed 27 published studies examining a possible association between sensory
      (visual or hearing) impairment and late-life psychosis with paranoid features. A
      majority of these investigations supported the postulated association between
      hearing impairment and late-onset schizophrenia or paranoid disorder. Many of the
      published studies, however, had important methodological limitations. In a case
      control study, we assessed visual and hearing impairments in 87 middle-aged and
      elderly subjects (16 with late-onset schizophrenia, 25 with early-onset
      schizophrenia, 20 with mood disorder, and 26 normal comparison subjects). Visual
      and hearing impairments were assessed in a blind manner by means of standardized
      quantitative assessments. Compared with normal subjects, both of the
      schizophrenia groups and the mood disorder group had greater impairment in most
      variables of corrected visual acuity and in self-reported hearing deficit, but
      not in uncorrected (constitutional) visual acuity or on pure-tone audiometry. Our
      results suggest that the observed relationship between sensory impairment and
      late-life psychosis may be due, at least in part, to a suboptimal correction of
      sensory deficits in older psychiatric patients.

PMID- 8303226
TI  - Brain imaging in late-life schizophrenia and related psychoses.
AB  - Despite disagreements about nomenclature, patients who develop schizophrenic or
      schizophrenia-like symptoms in later life are often seen in clinical practice.
      Questions about the etiology of late-life psychotic disorders and about their
      similarities or differences from early-onset disorders remain unanswered. Neuro
      imaging techniques have been used to study patients with late onset of psychosis,
      and in substantial subgroups of patients (from 25% to 100% in various studies)
      compared with age-matched control subjects, structural and functional
      abnormalities have been found. We review the literature on imaging in late-life
      schizophrenia and related psychotic disorders, and we present data from our own
      investigations of patients with these disorders. We discuss the potential
      usefulness of imaging evaluations in patients with late-onset disorders, and we
      offer suggestions for future investigations.

PMID- 8303227
TI  - Quantitative D2 dopamine receptor PET and structural MRI changes in late-onset
      schizophrenia.
AB  - Late-onset schizophrenia (LOS) is likely a syndrome of diverse etiology. In a
      series of related studies, we compared LOS patients with normal controls, elderly
      patients with early-onset schizophrenia (EOS), and Alzheimer's disease patients,
      using magnetic resonance imaging (MRI) and neuroreceptor positron emission
      tomography measures, which had previously been reported to be abnormal in EOS.
      EOS and LOS patients showed similar MRI changes. LOS drug-naive patients had
      elevated Bmax (receptor density) values for dopamine D2 receptors compared with
      age and gender norms, a phenomenon previously reported by our group in young
      schizophrenia patients.

PMID- 8303228
TI  - Course of schizophrenia: neuropsychological evidence for a static encephalopathy.
AB  - The course of cognitive function in schizophrenia has often been debated. In one
      view, it is thought to be akin to that of a progressive dementia with relentless
      cognitive decline. In another view, the deficits are thought to remain relatively
      stable, analogous to those of a static encephalopathy. Review of longitudinal and
      cross-sectional studies strongly supports the latter interpretation. In
      particular, we present data from a recent cross-sectional study in which cohorts
      of patients in their third, fourth, fifth, sixth, and seventh decades of life
      were administered a battery of tests known to be sensitive to progressive
      dementing diseases. All patients were carefully screened to exclude those with
      neurologic, systemic, or psychiatric comorbid conditions, and cohorts were
      matched on estimated premorbid intellectual capacity. Although scores on most
      tests were impaired, no evidence of decline across groups was observed. These
      results are also consistent with neuroimaging and neuropathological studies in
      that no evidence for an active degenerative process has been discovered.

PMID- 8303229
TI  - Alzheimer-type neuropathology in elderly schizophrenia patients.
AB  - Traditionally, schizophrenia has been studied in early adulthood. Its course and
      outcome during senescence are largely unknown and subject to controversy. We
      reviewed the consecutive neuropathologic records of 1,046 patients who were
      chronically hospitalized in New York State mental institutions, and we selected
      for analysis all 802 patients who died after age 50 with a clinical antemortem
      diagnosis, as recorded in the autopsy notes, of schizophrenia (n = 544) or
      dementia (n = 258). The prevalence of neuropathologic diagnoses consistent with
      Alzheimer's disease (AD) was 51 percent in the dementia group and 28 percent in
      the schizophrenia sample. This prevalence rate in the schizophrenia sample (mean
      age = 77) was considerably higher than that estimated for the general population.
      When evaluated against age of death, AD findings in demented patients were age
      invariant, whereas the rate of such findings in schizophrenia patients rose
      monotonously from under 5 percent below age 60 to 50 percent at age 90 and over.
      The age-relative rate of AD diagnosis in schizophrenia patients was similar to a
      curve postulated for first-degree relatives of familial AD patients and was
      markedly higher than population estimates. These findings as a basis for
      comparison with other retrospective studies of pathological records are
      presented. Our own study, as well as others, suffers from three intrinsic
      limitations. The clinical diagnoses are taken from death notes and have no formal
      verification. Likewise, neuropathologic diagnoses were based upon informal
      criteria in use at the time; since that time, formal diagnostic criteria have
      been evolving, and new staining methods have become available. Finally, it is not
      possible to determine from this material whether these patients are
      representative of all elderly schizophrenia patients or even of those who are
      institutionalized. Therefore, despite the large sample size on which our current
      findings are based, a new study has begun to address these weaknesses by complete
      review and rediagnosis of medical records and neuropathological material, using
      current methods, standardized criteria, and quantitative measures of degenerative
      changes. Specifically, the new ongoing study examines whether autopsied patients
      are representative by performing detailed diagnostic reviews of a control sample
      of nonautopsied patients from the same institutions. These results, if confirmed
      in the new study, demonstrate substantially greater vulnerability of chronic
      schizophrenia patients to the development of AD (or, at least, to histological
      changes typical of this disease). Possible association with chronic neuroleptic
      treatment and pathophysiological mechanisms remains to be elucidated.

PMID- 8303230
TI  - Schizophrenia with onset in adolescence: an 11-year followup.
AB  - This study examined the course of illness and factors affecting it in
      schizophrenias with onset between the ages of 14 and 18. Noteworthy in comparison
      to findings from other followup studies is the higher proportion of chronic
      courses of illness, about 50 percent. In addition, the type of course of illness
      corresponds in general with the treatment status. A possible explanation for this
      observation is the early age of onset, at which point the patient has not yet
      developed a sufficient degree of social and emotional independence and maturity
      before developing a schizophrenic psychosis. The age of onset is also shown to be
      an important predictor for the overall course of illness, as in other studies.

PMID- 8303232
TI  - First person account: How do I let go?

PMID- 8303231
TI  - Who should receive high-cost mental health treatment and for how long?
AB  - The use of some recently developed and promising mental health treatments is
      likely to be restricted by their high cost. Cost-effectiveness studies, however,
      suggest that high treatment costs may be offset by associated reductions in
      inpatient service use. In view of the considerable variation in the cost of
      inpatient treatment for the mentally ill, it may be cost-efficient to use high
      cost treatments for frequent hospital users but not for others. To illustrate
      this principle, we examine 9-year trends in inpatient costs incurred by
      schizophrenia patients discharged from Department of Veterans' Affairs medical
      centers across the country in fiscal year (FY) 1982. Even in the absence of
      specific intervention, average inpatient costs in this sample fell 49 percent,
      from $7,368 per patient in FY 1983 to $3,770 per patient in FY 1990, reducing the
      potential for inpatient cost offsets over time. Sensitivity analyses of potential
      inpatient cost offsets were conducted using a range estimate both for the cost of
      treatment and for resulting reductions in inpatient expense. Assuming
      effectiveness in a middle range, high-cost intervention was projected to be cost
      neutral for the 25 percent of the sample with the highest rates of baseline
      hospital use for a duration of 1-3 years. Although our specific model had low
      predictive power, the projection of cost offsets in large mental health systems
      deserves further examination and may prove to be one useful criterion, in
      addition to clinical effectiveness, for selecting patients to receive expensive
      treatment.

PMID- 8303233
TI  - Effects of thematic and lexical priming on readers' eye movements.
AB  - The study was inspired by Ehrlich & Rayner (1981). In the study semantic context
      effects were investigated during on-line discourse processing. Readers' eye
      movements were registered to see whether words that were semantically closely
      related to the global theme of the text were read faster than words that did not
      have any apparent semantic link to the discourse theme. In addition, lexical
      priming was examined by presenting an identity prime earlier in the text. The
      results showed that non-thematic words were regressed to more often than thematic
      words. Regressions were typically initiated after reaching a clause or sentence
      boundary. Regressions were thus assumed to be made in order to integrate non
      thematic words into the previous context. Modest negative correlations were found
      between word's fixation time and its relative predictability. No effects of
      lexical priming were observed. It was concluded that moderately constraining
      discourse contexts produce negligible effects on word recognition.

PMID- 8303234
TI  - Conditioned nausea after cancer chemotherapy and autonomic nervous system
      conditionability.
AB  - There are marked individual differences in conditioned nausea after cancer
      chemotherapy. To examine if part of this variation is associated with individual
      differences in autonomic nervous system conditionability, the present study
      addressed whether patients with conditioned nausea acquired conditioned heart
      rate and electrodermal responses at a different rate than patients without
      conditioned nausea. Of 28 relapse-free patients who had completed cisplatinum
      treatment for testicular cancer between 1981 and 1986, 10 reported persistent
      conditioned nausea, 8 extinguished conditioned nausea and 10 no conditioned
      nausea. These three groups were subjected to a differential conditioning paradigm
      with 8 sec pictorial stimuli (circles and triangles) serving as conditioned
      stimuli for an unconditioned electric shock while heart rate and electrodermal
      activity was monitored. There were 4 habituation, 8 acquisition and 8 extinction
      trials with each of the two cues. Analyses of variance using nausea status as the
      independent variable and physiological responses as the dependent lended some
      support to the notion that conditioned heart rate deceleration developed in
      response to the reinforced compared to the nonreinforced cue during acquisition
      in the two groups with persistent or extinguished conditioned nausea but not in
      the group with no conditioned nausea. In addition, patients that displayed good,
      as compared to poor heart rate conditionability during acquisition, were more
      likely to have persistent conditioned nausea, whereas those who showed poor heart
      rate conditioning mostly were those without conditioned nausea. Electrodermal
      variables revealed no systematic differences between groups. This tentatively
      supports that individual differences in parasympathetic but not sympathetic
      nervous system conditionability may be associated with individual differences in
      conditioned nausea resulting from cancer chemotherapy.

PMID- 8303235
TI  - Cerebral asymmetry in autonomic conditioning to facial expressions: sex
      differences.
AB  - In the present experiment, sex differences in hemispheric asymmetry during
      classical conditioning to emotional stimuli are reported. 125 subjects (62
      females and 63 males) were shown a slide of a happy face in the right (or left)
      visual half field (VHF), and simultaneously a slide of an angry face in the left
      (or right) VHF. Eight groups were formed by the combination of male and female
      subjects; left and right VHF positions of the angry/happy faces; and the
      administration/omission of the shock unconditioned stimulus (UCS). Dependent
      measures were skin conductance responses recorded from both hands. The results
      during extinction showed a significant larger SCR magnitude to the shock compared
      to the no-shock groups only for the female subjects. CS position during
      conditioning was also important in revealing differential responding to either
      the happy or angry faces. A right hemisphere effect was found for the angry face
      CS for both the male and female subjects, however with a greater difference for
      the females.

PMID- 8303236
TI  - Cardiovascular and neuroendocrine activity in preschool children: comparison
      between day-care and home levels.
AB  - Thirty boys and 30 girls at nine day-care centers were examined at the mean age
      of 3.5 and 5.5 with regard to systolic and diastolic blood pressure, heart rate
      and neuroendocrine activity (urinary catecholamines and cortisol) during a day at
      their day-care center and in their home, respectively. Compared to home levels,
      day-care was associated with increased heart rate, epinephrine and norepinephrine
      excretion and decreased cortisol levels. Systolic blood pressure decreased at the
      day-care centers at the age of 3.5 and increased at the age of 5.5. No
      significant sex differences were found. The possible role of mental and physical
      arousal and the dissociation between the sympathetic-adrenal medullary and the
      pituitary-adrenal cortical responses are discussed.

PMID- 8303237
TI  - Coronary-prone behavior may be declining in Danish men and women.
AB  - Four hundred males and four hundred females were randomly selected from the
      Danish population and received the Jenkins Activity Survey (JAS) on two
      occasions, once in 1988 and again in 1992. The JAS was rated by the standard
      procedure, providing a measure of the degree of time urgency and ambitiousness
      (Factor A), speed and impatience (Factor S), hard-driving and competitiveness
      (Factor H) and job involvement (Factor J) shown by the subjects. The scores
      obtained for all four factors tended to be lower in 1992 than in 1988, and the
      differences were significant for Factor H. In addition, gender differences were
      observed for Factors A, S and J, with higher scores being obtained by males than
      by females. Age-related differences were observed for Factors A and J. The
      findings indicate that Type A behaviors have declined during the past four years
      in the Danish adult population and that different strategies may be required for
      encouraging health behaviors in men and women.

PMID- 8303238
TI  - [Europe remains current].

PMID- 8303239
TI  - [Scotchbond from 1983 to 1992. The history of a market setter reflected in the
      literature. A review of the literature].
AB  - In this critical literature review 140 [correction of 136] publications dealing
      with Scotchbond were chronologically compiled since 1983 when Scotchbond was
      introduced to the dental market. The publications dealing with dentinal bonding
      were analyzed. Critical statements were predominant in the in-vivo- as well as in
      the in-vitro-studies. The literature reviewed for a period of ten years clearly
      demonstrated that the expectations created by the manufacturer and some initial
      studies concerning dentinal bonding did not become true. Long before private
      practitioners realized that Scotchbond didn't live up to the standards promised
      by the manufacturer, independent scientists had doubted the efficiency of the
      product. The conflict between market orientated and objective information for the
      private practitioners becomes obvious in this literature review.

PMID- 8303240
TI  - [Chemical and traumatic irritation of a canine premolar tooth germ].
AB  - The arrest of a premolar bud was observed in an animal experiment that was
      designed to study the influence of endodontic treatment in dogs' temporary teeth
      on the eruption of their permanent successors. A chemical irritation was induced
      by the burst of ZOE (zinc oxide and eugenol) into the dental follicle. Moreover,
      a mechanical trauma on the temporary molar was promoted by the dog's biting on
      its cage metallic bars. The devitalization effects were studied in thick
      undecalcified ground sections which were subjected to microradiographic analysis,
      to UV light microscopy in order to detect the fluorescent indicators of
      calcification, and finally to methylene blue staining. The arrest of the bud
      development was noted in fluorescent microscopic examination. Cellular cementum
      was formed on the pulpal surface of the dentine, while cementum, chondroid
      tissue, woven bone and lamellar bone developed in the pulpal tissue. These
      observations advise caution during root canal therapy of temporary teeth,
      especially those that are exposed to mechanical trauma. Such as the upper
      incisors.

PMID- 8303241
TI  - [Facial pains and disorders of the masticatory function. A retrospective analysis
      of the first 2 years of the activities of a multidisciplinary group at the
      University of Geneva].

PMID- 8303242
TI  - [The laser in periodontal therapy. A critical review].

PMID- 8303244
TI  - [The influence of the organs of the European Community on the activities of
      dentists].

PMID- 8303243
TI  - [European Community rights].

PMID- 8303245
TI  - [The migration of dentists in Europe].

PMID- 8303246
TI  - [Without Europe it will not work].

PMID- 8303247
TI  - [The growing number of older people in our society is becoming even more marked].

PMID- 8303248
TI  - [Pronation from the viewpoint of the transfer of movement between the calcaneus
      and the tibia].
AB  - Excessive foot eversion and abnormal tibial rotation have been associated with
      knee injuries. Why and whether or not overpronation in athletes leads to overuse
      injuries at the knee joint, however, is still not understood. It could be that
      this is related to the mechanical coupling at the ankle joint complex. The
      purpose of this study was to quantify the movement transferred from calcaneal
      eversion-inversion into tibial rotation, and vice-versa from tibial rotation into
      calcaneal eversion-inversion. Fourteen foot-leg specimens were used for
      investigation. A holding device with six degrees of freedom was constructed which
      allowed to rotate the calcaneus and to determine the resulting tibial rotation,
      and vice-versa. The movement transfer between calcaneus and tibia varied
      substantially, and it was not the same for both input modes. In the case of
      applied internal tibial rotation no calcaneal eversion was found. Apparently, the
      movement transfer depends from the individual mechanical coupling at the ankle
      joint complex. Excessive calcaneal eversion does only result in excessive
      rotational loading of the knee joint when coupled with a high movement transfer
      at the ankle joint complex. Finally, the results imply that, during gait,
      pronation results from ground reaction forces acting on the calcaneus, since
      internal tibial rotation is not transferred into calcaneal eversion.

PMID- 8303249
TI  - [Static deviations in high-performance athletes].

PMID- 8303250
TI  - [Methodological studies on estimating the loss of sodium, potassium, calcium and
      magnesium exemplified by a 10-km run].
AB  - An estimation of the electrolytic losses through the skin was evaluated in a run
      over a distance of 10 km on a 400 m track. Na, K, Ca and Mg excreted by the skin
      were collected in standardised clothes and thereafter washed out. The remaining
      electrolytes on the skin were collected by washing the body with deionized water.
      In addition the concentrations of hormones and metabolites in blood before and
      after the race were measured. Mean ambient temperature and relative humidity
      amounted to 21 degrees C and 35%, respectively. The mean performance was 40.5
      min. and the average body weight loss was 1.45 kg (1.95% of body weight). The
      only significant changes in the serum concentrations were the increases of free
      fatty acids and glycerol. This can be explained, together with a slight increase
      of glucose and a decrease of insulin, by a higher sympathoadrenergic activity. In
      the mean 20 mg calcium, 5 mg magnesium, 200 mg potassium and 800 mg sodium were
      lost by the skin per kg body weight loss. These values compared well with
      corresponding data found in literature. The described method can therefore be
      proposed for further experiments.

PMID- 8303251
TI  - [Normobaric oxygenation as a first-aid measure in decompression sickness].
AB  - Most divers and diving medicine specialists know that application of normobaric
      oxygen as first aid after a bubble disease incident is highly effective. However,
      as yet technical difficulties acted as a deterrent to using normobaric oxygen at
      the diving site. This can now be overcome by a newer technique. To be efficient,
      any therapy of bubble disease should follow three main principles: maximal
      partial pressure of inhaled oxygen (i.e. 100 kpa in normobaric, and 280 kpa in
      hyperbaric conditions); minimal partial pressure of inhaled nitrogen, which
      should ideally be near zero; immediate start of therapy, if possible at the
      diving site, but not later than 2 hours after the onset of the first symptoms.
      However, it has to be borne in mind that for an efficient normobaric oxygenation
      (100%), the standard apparatus design without oxygen reservoir is obsolete, for
      it offers at most 40% oxygen to the lungs. Currently the following technical
      approaches for an efficient normobaric oxygenation are available: open one-way
      systems with tightly fitting mask and oxygen reservoir bag (type Ambu or Leardal,
      etc.); open systems with on-demand regulation and tightly fitting mouth piece
      (type SCUBA, or Bird-respirator); closed systems with CO2 absorber (type oxygen
      rebreathing diving gear). The closed system is a genuine technical advance,
      because it needs 15 times less oxygen than open systems (about 90 liters oxygen
      for a 3-hours oxygenation run). Such an apparatus is thus of light weight, far
      less cumbersome, and nevertheless highly efficient. The therapy should start
      immediately at the site of the mishap and be maintained during the transport to
      the next HBO-unit (usually 3 to 6 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8303252
TI  - [Preliminary diagnostic measures for performing hyperbaric oxygen therapy in a
      diving accident].
AB  - A diving accident may occur during working and leisure time, scientific or
      archaeological investigations, even during police duty. It is therefore necessary
      to carry out several preventive measures. The therapeutic treatment based on
      oxyhyperbaric recompression, is a medical therapy that needs a precise diagnosis
      and an evaluation of contingent associated pathologies. The following elements
      have to be checked on the diving place: the anamnestic data, the diving outline
      and the symptomatology, together with the usual clinical tests. The clinical
      survey will be completed in hospital, including electrocardiogram, thorax x-ray
      and laboratory tests. CT-scan, NMR and Evoked Potentials may be considered
      complementary actions to be taken, according to perceived needs.

PMID- 8303253
TI  - Orf virus infection in pregnancy.
AB  - Orf virus infection is endemic among sheep and goats, and can occur in humans who
      handle these animals. Orf virus infection in humans causes a characteristic skin
      lesion, and systemic symptoms can occur. Very little is known about Orf virus
      infection in human pregnancy. A case of Orf virus infection, with onset at 33
      weeks gestation, is presented. There were no pathological findings in the infant
      born at term, or in the placenta.

PMID- 8303254
TI  - It's kind of hard to explain in court.

PMID- 8303255
TI  - Noncompliance: a modern disease with only symptomatic treatment.

PMID- 8303256
TI  - A brief history of medical diagnosis.

PMID- 8303257
TI  - Reflections on the environment.

PMID- 8303258
TI  - ORI and misconduct investigations.

PMID- 8303259
TI  - Bringing science back to the neighborhood.

PMID- 8303260
TI  - Triple repeat DNA as a highly mutable regulatory mechanism.

PMID- 8303261
TI  - New fight over fetal tissue grafts.

PMID- 8303262
TI  - Fetal tissue research on the rebound.

PMID- 8303263
TI  - National Institutes of Health. New law brings affirmative action to clinical
      research.

PMID- 8303264
TI  - National Institutes of Health. Panel proposes guidelines for industry.

PMID- 8303265
TI  - A costly settlement ends whistle-blower suit.

PMID- 8303266
TI  - New tool for predicting AIDS onset?

PMID- 8303267
TI  - Embryology. Watching new developments--live.

PMID- 8303268
TI  - Ex-defense scientists come in from the cold.

PMID- 8303269
TI  - Remodeling schemes of intracellular pathogens.

PMID- 8303270
TI  - DNA replication origins in animal cells: a question of context?

PMID- 8303271
TI  - Routes to catalysis: structure of a catalytic antibody and comparison with its
      natural counterpart.
AB  - The three-dimensional structure of a catalytic antibody (1F7) with chorismate
      mutase activity has been determined to 3.0 A resolution as a complex with a
      transition state analog. The structural data suggest that the antibody stabilizes
      the same conformationally restricted pericyclic transition state as occurs in the
      uncatalyzed reaction. Overall shape and charge complementarity between the
      combining site and the transition state analog dictate preferential binding of
      the correct substrate enantiomer in a conformation appropriate for reaction.
      Comparison with the structure of a chorismate mutase enzyme indicates an overall
      similarity between the catalytic mechanism employed by the two proteins.
      Differences in the number of specific interactions available for restricting the
      rotational degrees of freedom in the transition state, and the lack of multiple
      electrostatic interactions that might stabilize charge separation in this highly
      polarized metastable species, are likely to account for the observed 10(4) times
      lower activity of the antibody relative to that of the natural enzymes that
      catalyze this reaction. The structure of the 1F7 Fab'-hapten complex provides
      confirmation that the properties of an antibody catalyst faithfully reflect the
      design of the transition state analog.

PMID- 8303272
TI  - Electric field-induced concentration gradients in lipid monolayers.
AB  - Externally applied electric field gradients gave rise to lateral concentration
      gradients in monolayers of certain binary lipid mixtures. For binary mixtures of
      dihydrocholesterol and dimyristoylphosphatidylcholine, the application of an
      electric field gradient at pressures below the critical pressure produced a
      liquid-liquid phase separation in a monolayer that is otherwise homogenous. At
      pressures slightly above the critical pressure, a field gradient produced a large
      concentration gradient without phase separation. The lipid concentration
      gradients can be described by equilibrium thermodynamic chemical potentials. The
      observed effects appear to be relevant to the structure and composition of
      biological membranes.

PMID- 8303273
TI  - Mortality rates in a genetically heterogeneous population of Caenorhabditis
      elegans.
AB  - Age-specific mortality rates in isogenic populations of the nematode
      Caenorhabditis elegans increase exponentially throughout life. In genetically
      heterogeneous populations, age-specific mortality increases exponentially until
      about 17 days and then remains constant until the last death occurs at about 60
      days. This period of constant age-specific mortality results from genetic
      heterogeneity. Subpopulations differ in mean life-span, but they all exhibit near
      exponential, albeit different, rates of increase in age-specific mortality. Thus,
      much of the observed heterogeneity in mortality rates later in life could result
      from genetic heterogeneity and not from an inherent effect of aging.

PMID- 8303274
TI  - Zinc finger phage: affinity selection of fingers with new DNA-binding
      specificities.
AB  - A phage display system was developed and used to select zinc finger proteins with
      altered DNA-binding specificities. The three zinc fingers of the Zif268 protein
      were expressed on the surface of filamentous phage, and a library of variants was
      prepared by randomizing critical amino acids in the first zinc finger. Affinity
      selections, using DNA sites with base changes in the region recognized by the
      first finger, yielded Zif268 variants that bound tightly and specifically to the
      new sites. This phage system provides a tool for the study of protein-DNA
      interactions and may offer a general method for selecting zinc finger proteins
      that recognize desired target sites on double-stranded DNA.

PMID- 8303275
TI  - Levels of peripheral T cell tolerance induced by different doses of tolerogen.
AB  - Antigen-specific immunosuppression requires an understanding of the parameters
      that control peripheral T cell tolerance. A liver-specific inducible promoter was
      used to drive the expression of the major histocompatibility complex antigen Kb
      in transgenic mice. Minute amounts of Kb, expressed exclusively on hepatocytes,
      induced tolerance by partial down-regulation of the T cell receptor (TCR) on the
      self-reactive CD8+ cells. Contact of these tolerant T cells with high
      concentrations of Kb after induction led to complete down-regulation of TCR.
      Thus, tolerant T cells are susceptible to further tolerogenic signals and reach
      different levels of tolerance depending on antigen dose.

PMID- 8303276
TI  - Natural vertical transmission of western equine encephalomyelitis virus in
      mosquitoes.
AB  - The mechanism by which western equine encephalomyelitis (WEE) virus and other
      mosquito-borne alphaviruses (Togaviridae) survive during periods of vector
      inactivity is unknown. Recently, three strains of WEE virus were isolated from
      adult Aedes dorsalis collected as larvae from a salt marsh in a coastal region of
      California. This provides evidence of vertical transmission of WEE virus in
      mosquitoes in nature. Vertical transmission in Ae. dorsalis and closely related
      mosquito species may be an important mechanism for the maintenance of WEE virus
      in temperate regions in North America where horizontal transmission of the virus
      is seasonal.

PMID- 8303277
TI  - Lack of acidification in Mycobacterium phagosomes produced by exclusion of the
      vesicular proton-ATPase.
AB  - The success of Mycobacterium species as pathogens depends on their ability to
      maintain an infection inside the phagocytic vacuole of the macrophage. Although
      the bacteria are reported to modulate maturation of their intracellular vacuoles,
      the nature of such modifications is unknown. In this study, vacuoles formed
      around Mycobacterium avium failed to acidify below pH 6.3 to 6.5. Immunoelectron
      microscopy of infected macrophages and immunoblotting of isolated phagosomes
      showed that Mycobacterium vacuoles acquire the lysosomal membrane protein LAMP-1,
      but not the vesicular proton-adenosine triphosphatase (ATPase) responsible for
      phagosomal acidification. This suggests either a selective inhibition of fusion
      with proton-ATPase-containing vesicles or a rapid removal of the complex from
      Mycobacterium phagosomes.

PMID- 8303278
TI  - Disruption of PDGF receptor trafficking by mutation of its PI-3 kinase binding
      sites.
AB  - Human platelet-derived growth factor receptors (PDGFRs) expressed in human Hep G2
      cells internalized and concentrated in a juxtanuclear region near the Golgi
      network within 10 minutes after the cells were treated with PDGF. A PDGFR mutant
      (F5) that lacks high-affinity binding sites for the Src homology 2 domain
      containing proteins phosphatidylinositol-3 kinase (PI-3 kinase), Ras guanosine
      triphosphatase activating protein, phospholipase C-gamma, and a phosphotyrosine
      phosphatase (Syp) remained at the cell periphery. Restoration of the PI-3 kinase
      binding sites on F5 completely restored the ability of the receptor to
      concentrate intracellularly. A PDGFR mutant lacking only PI-3 kinase binding
      sites failed to concentrate intracellularly. Thus, PI-3 kinase binding sites
      appear both necessary and sufficient for the normal endocytic trafficking of the
      activated PDGFR.

PMID- 8303280
TI  - Associative odor learning in Drosophila abolished by chemical ablation of
      mushroom bodies.
AB  - The corpora pedunculata, or mushroom bodies (MBs), in the brain of Drosophila
      melanogaster adults consist of approximately 2500 parallel Kenyon cell fibers
      derived from four MB neuroblasts. Hydroxyurea fed to newly hatched larvae
      selectively deletes these cells, resulting in complete, precise MB albation.
      Adult flies developing without MBs behave normally in most respects, but are
      unable to perform in a classical conditioning paradigm that tests associative
      learning of odor cues and electric shock. This deficit cannot be attributed to
      reductions in olfactory sensitivity, shock reactivity, or locomotor behavior. The
      results demonstrate that MBs mediate associative odor learning in flies.

PMID- 8303281
TI  - NIH neural transplantation funding.

PMID- 8303279
TI  - Adenosine inhibition of mesopontine cholinergic neurons: implications for EEG
      arousal.
AB  - Increased discharge activity of mesopontine cholinergic neurons participates in
      the production of electroencephalographic (EEG) arousal; such arousal diminishes
      as a function of the duration of prior wakefulness or of brain hyperthermia.
      Whole-cell and extracellular recordings in a brainstem slice show that
      mesopontine cholinergic neurons are under the tonic inhibitory control of
      endogenous adenosine, a neuromodulator released during brain metabolism. This
      inhibitory tone is mediated postsynaptically by an inwardly rectifying potassium
      conductance and by an inhibition of the hyperpolarization-activated current.
      These data provide a coupling mechanism linking neuronal control of EEG arousal
      with the effects of prior wakefulness, brain hyperthermia, and the use of the
      adenosine receptor blockers caffeine and theophylline.

PMID- 8303283
TI  - AIDS institute in turmoil.

PMID- 8303282
TI  - Alloimmunization to prevent AIDS?

PMID- 8303284
TI  - R&D budget: growth in hard times.

PMID- 8303285
TI  - Hughes to add 49 new investigators.

PMID- 8303286
TI  - Academy warns against slipping ethics.

PMID- 8303287
TI  - Genetic engineering. Safety concerns halt U.K. study.

PMID- 8303288
TI  - Chernobyl explosion. Inside look confirms more radiation.

PMID- 8303289
TI  - U.S. research forum fails to find a common front.

PMID- 8303290
TI  - Cell suicide: by ICE, not fire.

PMID- 8303291
TI  - Will molecular data set the stage for a synthesis?

PMID- 8303292
TI  - Protein-DNA recognition: new perspectives and underlying themes.

PMID- 8303293
TI  - Population policy options in the developing world.
AB  - The population of the developing world is currently expanding at the
      unprecedented rate of more than 800 million per decade, and despite anticipated
      reductions in growth during the 21st century, its size is expected to increase
      from 4.3 billion today to 10.2 billion in 2100. Past efforts to curb this growth
      have almost exclusively focused on the implementation of family planning programs
      to provide contraceptive information, services, and supplies. These programs have
      been partially successful in reducing birth rates. Further investments in them
      will have an additional but limited impact on population growth; therefore, other
      policy options, in particular measures to reduce high demand for births and limit
      population momentum, are needed.

PMID- 8303294
TI  - Coupling of local folding to site-specific binding of proteins to DNA.
AB  - Thermodynamic studies have demonstrated the central importance of a large
      negative heat capacity change (delta C degree assoc) in site-specific protein-DNA
      recognition. Dissection of the large negative delta C degree assoc and the
      entropy change of protein-ligand and protein-DNA complexation provide a
      thermodynamic signature identifying processes in which local folding is coupled
      to binding. Estimates of the number of residues that fold on binding obtained
      from this analysis agree with structural data. Structural comparisons indicate
      that these local folding transitions create key parts of the protein-DNA
      interface. The energetic implications of this "induced fit" model for DNA site
      recognition are considered.

PMID- 8303295
TI  - Green fluorescent protein as a marker for gene expression.
AB  - A complementary DNA for the Aequorea victoria green fluorescent protein (GFP)
      produces a fluorescent product when expressed in prokaryotic (Escherichia coli)
      or eukaryotic (Caenorhabditis elegans) cells. Because exogenous substrates and
      cofactors are not required for this fluorescence, GFP expression can be used to
      monitor gene expression and protein localization in living organisms.

PMID- 8303296
TI  - RNA polymerase II initiation factor interactions and transcription start site
      selection.
AB  - An RNA polymerase II transcription system was resolved and reconstituted from
      extracts of Schizosaccharomyces pombe. Exchange with components of a
      Saccharomyces cerevisiae system was undertaken to reveal the factor or factors
      responsible for the difference in location of the transcription start site, about
      30 base pairs and 40 to 120 base pairs downstream of the TATA box in S. pombe and
      S. cerevisiae, respectively. Two components, counterparts of human transcription
      factor IIF (TFIIF) and TFIIH, could be exchanged individually between systems
      without effect on the start site. Three components, counterparts of human TFIIB,
      TFIIE, and RNA polymerase II, could not be exchanged individually but could be
      swapped in the pairs TFIIE-TFIIH and TFIIB-RNA polymerase II, which demonstrates
      that there are functional interactions between these components. Moreover,
      exchange of the latter pair shifted the starting position, which shows that TFIIB
      and RNA polymerase II are solely responsible for determining the start site of
      transcription.

PMID- 8303297
TI  - Transcriptional activation modulated by homopolymeric glutamine and proline
      stretches.
AB  - Many transcription factors contain proline- or glutamine-rich activation domains.
      Here it is shown that simple homopolymeric stretches of these amino acids can
      activate transcription when fused to the DNA binding domain of GAL4 factor. In
      vitro, activity increased with polymer length, whereas in cell transfection
      assays maximal activity was achieved by 10 to 30 glutamines or about 10 prolines.
      Similar results were obtained when glutamine stretches were placed within a
      [GAL4]-VP16 chimeric protein. Because these stretches are encoded by rapidly
      evolving triplet repeats (microsatellites), they may be the main cause for
      modulation of transcription factor activity and thus result in subtle or overt
      genomic effects.

PMID- 8303298
TI  - Promoter-selective transcriptional defect in cell cycle mutant ts13 rescued by
      hTAFII250.
AB  - The TAFII250 subunit of the human transcription factor IID (TFIID) rescues the
      temperature-sensitive hamster cell line ts13 and overcomes a G1 arrest.
      Investigation of the transcriptional properties of ts13 nuclear extracts in vitro
      showed that activation by the site-specific regulators Sp1 and Gal4VP16 is
      temperature sensitive in ts13 extracts, whereas basal transcription remains
      unaffected. This transcriptional defect can be rescued by purified human TFIID or
      by expression of wild-type TAFII250 in ts13 cells. Expression from the cyclin A
      but not c-fos promoter is temperature sensitive in these mutant cells. Thus, the
      mutation in TAFII250 appears to have gene-specific effects that may lead to the
      ts13 cell cycle phenotype.

PMID- 8303299
TI  - Mapping the lectin-like activity of tumor necrosis factor.
AB  - Tumor necrosis factor (TNF), but not lymphotoxin (LT), is directly trypanolytic
      for salivarian trypanosomes. This activity was not blocked by soluble 55
      kilodalton and 75-kilodalton TNF receptors, but was potently inhibited by N,N'
      diacetylchitobiose, an oligosaccharide that binds TNF. Comparative sequence
      analysis of TNF and LT localized the trypanocidal region, and synthetic peptides
      were trypanolytic. TNF molecules in which the trypanocidal region was mutated or
      deleted retained tumoricidal activity. Thus, trypanosome-TNF interactions occur
      via a TNF domain, probably with lectin-like affinity, which is functionally and
      spatially distinct from the mammalian TNF receptor binding sites.

PMID- 8303300
TI  - Neuronal activity during different behaviors in Aplysia: a distributed
      organization?
AB  - The active neuronal populations in the Aplysia abdominal ganglion during
      spontaneous and evoked behaviors were compared with the use of multineuronal
      optical measurements. In some preparations, more than 90 percent of the neurons
      activated during the reflex withdrawal of the gill also were activated during
      respiratory pumping and during small spontaneous gill contractions. Although the
      same neurons made action potentials in all three behaviors, the activity patterns
      were different. There was a substantial interaction between the neural substrates
      underlying evoked and spontaneous behaviors when they were made to occur
      together. If a gill withdrawal reflex was elicited a few seconds after a
      respiratory pumping episode, the evoked neuronal activity in most neurons was
      clearly altered. These results suggest that a distributed organization involving
      a large number of neurons may be responsible for generating the two behaviors.
      Different behaviors appear to be generated by altered activities of a single,
      large distributed network rather than by small dedicated circuits.

PMID- 8303301
TI  - Prevention of vertebrate neuronal death by the crmA gene.
AB  - Interleukin-1 beta converting enzyme (ICE) is a mammalian homolog of CED-3, a
      protein required for programmed cell death in the nematode Caenorhabditis
      elegans. The activity of ICE can be specifically inhibited by the product of
      crmA, a cytokine response modifier gene encoded by cowpox virus. Microinjection
      of the crmA gene into chicken dorsal root ganglion neurons was found to prevent
      cell death induced by deprivation of nerve growth factor. Thus, ICE is likely to
      participate in neuronal death in vertebrates.

PMID- 8303302
TI  - Recent advances in vaccine development and delivery, adhesion molecules in the
      immune response, and bone marrow transplantation. Proceedings of a symposium.
      January 8-9, 1993, Palm Beach, Florida.

PMID- 8303303
TI  - Donor and host influences in bone marrow transplantation for immunodeficiency
      disease and leukemia.
AB  - Bone marrow transplantation is an effective form of therapy for lethal
      immunodeficiency diseases and leukemia. Patients who are treated by bone marrow
      transplantation for these diseases have an improved outcome if treated early
      after diagnosis, before they have developed secondary complications. Recent
      advances in transplantation have allowed choices between several donor types.
      These alternative donor types are the subject of this analysis from the
      University of Minnesota. In these diseases, matched sibling donor bone marrow
      transplantation is the standard for comparison. In individuals with lethal
      immunodeficiencies (severe combined immune deficiency [SCID], Wiskott-Aldrich
      syndrome [WAS], Chediak-Higashi syndrome [CHS]) who lack a sibling donor,
      unrelated transplantation has produced results that are almost equal to those of
      matched sibling transplants. Patients with high-risk acute lymphoblastic leukemia
      (ALL) who have received sibling or unrelated transplants have results that are
      superior to autologous donor transplants. In ALL, there is a need to use new
      therapies, eg, immunotoxins, to decrease the currently high relapse rate. In
      patients with acute myelogenous leukemia (AML) in first complete remission,
      results are excellent and comparable using related and autologous donors. Results
      in non-first-remission AML are inferior and do not differ if related, unrelated,
      or autologous transplants are used. In chronic myelogenous leukemia (CML), early
      survival results are superior using autologous and related transplants as
      compared with unrelated transplants.

PMID- 8303304
TI  - Graft-versus-host disease: host and donor views.
AB  - Major histocompatibility complex (MHC) antigens, termed HLA in man, provide the
      major barrier to transplantation. Clinical manifestations of the host-versus
      graft reaction are generally referred to as rejection and those of the graft
      versus-host (GVH) reaction as graft-versus-host disease (GVHD). GVHD can occur
      after transplantation of marrow or solid organs or transfusion of blood products.
      GVHD involves antigen-presenting cells, which are recognized by T lymphocytes via
      the T-cell receptor. CD4 and CD8 serve as accessory molecules. This interaction
      results in T-cell activation, expression of interleukin-2 receptors (IL-2R) and
      the production of IL-2 followed, generally, by clonal proliferation and
      differentiation associated with lymphokine secretion and dysregulation that may
      involve interferon-gamma; tumor necrosis factor-alpha; IL-2, -3, -4, -5, -6, and 
      9; granulocyte macrophage colony-stimulating factor (GM-CSF); and other factors.
      Effector cells such as cytotoxic T cells, natural killer (NK) cells, and
      macrophages become activated, mostly by bone marrow-derived lymphohemopoietic
      cells, and contribute to cell and tissue death. Many of the cytokines also alter
      vascular endothelium; conceivably these changes also affect homing of cells and
      allogeneic interactions. Another factor is the administration of in vivo GVHD
      prophylaxis, which may modify both undesirable (GVHD-inducing) and desirable
      (tolerance-inducing) mechanisms. Exogenous hematopoietic growth factors and
      cytokines recently introduced into clinical trials may interfere with endogenous
      feedback loops in a positive or negative fashion. Adverse reactions have been
      observed with IL-2 and with interferon. Potentially beneficial effects have been
      reported with the use of soluble IL-1R or IL-1R-antagonist.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8303305
TI  - The gene therapy of cancer: transgenic immunotherapy.
AB  - Gene therapy can be defined as the insertion of functional genes into cells to
      treat a disease. Cellular augmentation, whereby gene transfer confers a novel
      function to the cell, has proved to be useful in designing strategies for the
      treatment of cancer. In particular, a variety of cell types may be transduced
      with immune response genes that are intended to elicit a more effective immune
      attack against tumor cells. This process has been termed transgenic
      immunotherapy. Preclinical studies involving the transduction of tumor cells,
      stromal cells, and lymphocytes with a number of immune response genes have
      demonstrated potent cytotoxic lymphocyte responses against tumor cells, and in
      some cases the induction of long-lasting immunity against tumor rechallenge. It
      is hoped that this form of cancer immunotherapy will permit the development of
      vaccines effective in eradicating minimal residual disease and immunizing
      individuals at risk for cancer.

PMID- 8303306
TI  - New advances in vaccine delivery systems.
AB  - Successful application of the next generation of vaccines will require that
      protection be induced with a minimal number of administrations, and that a
      practical approach to inducing immunity at mucosal surfaces be developed. For
      these reasons, vaccine-containing microspheres were formulated from the
      biodegradable and biocompatible copolymer poly(DL-lactide-co-glycolide) [DL-PLG].
      Subcutaneous immunization of mice with 1- to 10-microns microspheres containing a
      toxoid vaccine of staphylococcal enterotoxin B (SEB) induced a 500-fold
      potentiation of the circulating antitoxin response. Strong adjuvant activity was
      dependent on the microspheres being no more than 10 microns in diameter and
      required that the antigen was within the particles. The rate of DL-PLG
      biodegradation is a function of the ratio of lactide to glycolide, and the co
      injection of SEB toxoid microspheres formulated with two different DL-PLG ratios
      stimulated both a primary and an anamnestic secondary antitoxin response. When it
      was administered by the oral or intratracheal (IT) route, microencapsulated SEB
      toxoid was found to be effective in the induction of concurrent circulating and
      disseminated mucosal antibody responses. Female rhesus macaques immunized with a
      microencapsulated simian immunodeficiency virus (SIV) vaccine produced high
      levels of circulating anti-SIV antibodies, and following oral or IT boosting,
      specific antibodies were found in vaginal wash fluids. Vaginal challenge with
      viable homologous SIV resulted in the infection of three out of four nonimmunized
      but only one out of seven microsphere-immunized macaques. Thus, DL-PLG
      microspheres are a promising approach to the delivery of vaccines, combining
      adjuvant activity with controlled release and effective presentation to mucosally
      associated lymphoid tissues (MALT).

PMID- 8303307
TI  - Antigen processing: a critical factor in rational vaccine design.
AB  - T lymphocytes play a critical role in host immunity, autoimmunity, and tissue
      rejection. There has been tremendous progress in understanding the molecular
      basis of T-cell recognition of foreign and self antigens. It is now well
      established that the major histocompatibility complex (MHC)-restricted nature of
      T-cell recognition is due to the interaction of the T-cell antigen receptor with
      MHC class I or II molecules bearing short peptides derived from antigenic
      proteins. In this report, we review recent progress in understanding antigen
      processing, ie, the mechanism by which antigenic peptides are generated in
      antigen-presenting cells and delivered to the appropriate MHC molecule in the
      appropriate intracellular compartment.

PMID- 8303308
TI  - New perspectives in mucosal immunity with emphasis on vaccine development.
AB  - In this review, we have purposely focused on five areas that are currently
      receiving extensive research attention and will be of major importance for
      development of mucosal and systemic immunity to oral vaccines. These five areas
      include the following: (1) helper T-cell (Th) subsets and cytokines for mucosal
      IgA responses; (2) Th1- and Th2-type subsets in regulation of mucosal IgA
      responses; (3) antigen uptake and presentation in the mucosal immune system; (4)
      the importance of memory in mucosal immunity to vaccines; and (5) the
      determination of whether oral immunization alone induces immunity in all mucosal
      effector tissues. It is now established that the mucosal immune system can be
      divided into discrete mucosal inductive sites where vaccines/antigens are
      encountered and taken up, processed, and presented to B and T cells, and separate
      areas where immune cells actually function (mucosal effector tissues). Further,
      through the help provided by Th cells and cytokines, the B cells respond to
      antigen and undergo expansion including memory cell formation. Following the
      migration of memory B cells to mucosal effector tissues, the cells rapidly
      develop into IgA plasma cells, and the prevalence of the latter cell type
      represents a major characteristic of mucosal effector tissues. It also appears
      that antigen-specific Th cells and perhaps even CD8+ cytotoxic T lymphocytes can
      make this circular journey (along with memory/activated B cells) from inductive
      to mucosal effector sites, and this is termed the common mucosal immune system
      (CMIS). The major implications of the CMIS for development of vaccines would
      include each of the five components that are discussed.

PMID- 8303309
TI  - Vaccinia virus: a novel approach for molecular engineering of peptide vaccines.
AB  - One of the more promising new approaches for producing prophylactic vaccines
      involves the genetic engineering of vaccinia virus (VV) strains to express a
      single protein, a portion of a protein, or a single epitope from a heterologous
      pathogen. As an example, the application of this approach to the prevention of
      streptococcal-related diseases is considered. Experiments are described in which
      several generations of VV-based recombinant vaccines were constructed that
      expressed various derivatives of the M protein gene from Streptococcus pyogenes
      (serotype 6). These recombinants were used to demonstrate the high-level
      expression, stability, and antigen authenticity of the bacterial proteins
      expressed in infected tissue culture cells. When tested in a mouse model system,
      immunization with the VV recombinants expressing specific subdomains of the M
      protein conferred protection to challenge from both homologous and heterologous
      serotypes of pathogenic streptococci.

PMID- 8303311
TI  - Regulation of T-cell adhesion to endothelium.

PMID- 8303310
TI  - Leukocyte-endothelial cell interactions.
AB  - Mechanisms that support migration of leukocytes have been studied extensively in
      vitro. The adhesion of neutrophils under conditions of flow at venous shear rates
      primarily involves members of the selectin family. E-selectin is upregulated by
      cytokine stimulation of endothelial cells (ECs); P-selectin is upregulated by
      stimulation of ECs with agents such as thrombin and histamine; and L-selectin is
      resident on the surface of unstimulated neutrophils. Each selectin allows
      neutrophils to roll under conditions of flow. Rolling neutrophils often stop on
      the EC surface and then rapidly transmigrate. The stationary adhesions and
      migration are heavily dependent on two members of the CD18 (beta 2) integrin
      family, CD11a/CD18 and CD11b/CD18, on the neutrophil surface, intercellular
      adhesion molecule-1 (ICAM-1) on ECs, and endothelial-derived chemoattractants
      such as interleukin-8 (IL-8). Chemokinetic activation of neutrophils at the
      endothelial surface induces a transition from selectin-dependent adhesion to
      CD18/ICAM-1-dependent transmigration that is most clearly evidenced by the
      shedding of L-selectin from the neutrophil surface and upregulation of CD11b/CD18
      to the neutrophil surface.

PMID- 8303312
TI  - Discovery of the leukocyte adherence defect--a historical perspective.
AB  - Leukocyte adherence deficiency (LAD) is characterized by bacterial infections at
      peripheral tissue sites whose defense requires exit of neutrophils from the
      vasculature. LAD is unique in that one of the basic and common cell properties,
      adherence, is involved in this defect in host defense. The molecular
      understanding of LAD catalyzed a continuing revolution in the investigation and
      understanding of cell adherence phenomena inside and outside of the immune
      system. The explosive gain of knowledge directly attributable to the recognition
      of LAD may make this disease the most important inborn error of host defense yet
      recognized. The recognition of this defect through the interaction of a number of
      investigators is explored in this report. An attempt is made to reveal the
      background events that made the discovery of this defect possible. The
      relationship between the understanding of the physiology of this disease and the
      rapid understanding of the molecular defect is examined. Finally, the
      significance of this disease and its understanding in relation to biologic
      discovery in general are discussed.

PMID- 8303313
TI  - The role of adhesion molecules in the regulation of antibody responses.
AB  - We used the T-cell-dependent antigen, bacteriophage (phage) phi X174, to study
      antibody synthesis in patients, guinea pigs, and dogs with complement component
      deficiencies (C2, C4, C3, C7); in patients with adhesion molecule deficiencies
      (CD11/CD18 or sialylated Lewisx); and in patients with the hyper IgM (HIM)
      syndrome (absence of functional gp39 expression by activated T cells). Patients
      and guinea pigs deficient in early complement components, patients deficient in
      CD11/CD18, and patients lacking functional gp39 on activated T cells responded to
      repeated phage immunizations with depressed antibody titers, lack of or
      inadequate amplification, and failure to switch from IgM to IgG, suggesting that
      defective T-cell-B-cell interaction is the cause of the antibody deficiency
      observed in these patients.

PMID- 8303314
TI  - The pruritus of cholestasis.

PMID- 8303315
TI  - Refractory ascites.
AB  - The first step in the approach to the ascites patient, after the history and
      physical examination, is to perform a diagnostic abdominal paracentesis for SAAG
      to determine whether portal hypertension is present (SAAG 1.1 g/dl or higher) or
      not (SAAG less than 1.1 gm/dl) (Table 1). Patients without portal hypertension
      probably do not have liver disease as the cause of their ascites formation and
      probably should not be treated with dietary sodium restriction and diuretics.
      Patients with portal hypertension-related ascites usually have chronic
      parenchymal liver disease and usually require hospitalization for diet education,
      diuretic treatment, and evaluation of the underlying liver disease. Approximately
      90% of patients with ascites due to chronic parenchymal liver disease respond to
      dietary sodium restriction and diuretics. Because of the poor prognosis
      associated with ascites, patients who are good candidates for transplantation
      should be considered for listing when they develop this complication of their
      underlying liver disease. The 10% of patients with cirrhosis whose ascites is
      refractory to routine medical treatment must be offered alternative therapy.
      Transplant candidates should be listed, in my opinion, once they are documented
      to have diuretic-resistant ascites. Fortunately, alcoholics (who are usually not
      good candidates for transplantation) who abstain from alcohol may revert from
      diuretic-resistant to diuretic-sensitive ascites over a period of months. Chronic
      outpatient therapeutic paracentesis is the most popular short-term treatment for
      patients with diuretic-resistant ascites. Paracentesis can be used as a "bridge"
      to alternative therapies or can be continued indefinitely.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8303316
TI  - The Budd-Chiari syndrome: a therapeutic Gordian knot?

PMID- 8303318
TI  - Management of osteopenia of liver disease with special emphasis on primary
      biliary cirrhosis.
AB  - Bone disease occurring in the setting of chronic liver disease is being
      recognized increasingly often. The osteopenia may be an important cause of
      morbidity in these patients, particularly as effective treatments become
      available for the liver diseases and especially if these treatments actually
      worsen the coexistent bone disease. Although no specific treatments are of proven
      benefit for the bone disease in most instances, adequate exercise and calcium
      intake as well as vitamin D supplementation when deficiencies are present are
      recommended for all patients. Information is lacking about specific treatment for
      patients with PSC, hemochromatosis, and alcoholic liver disease. For patients
      with PBC, other than the above general measures, preliminary information suggests
      that supplemental estrogens in postmenopausal women and the use of calcitonin may
      offer promise; both measures are deserving of further study in this group of
      patients.

PMID- 8303317
TI  - Antiviral therapy of the Asian patient with chronic hepatitis B.

PMID- 8303319
TI  - Hepatocellular carcinoma in cirrhotics.

PMID- 8303320
TI  - Treatment of alcoholic hepatitis.

PMID- 8303321
TI  - Difficult management problems in fulminant hepatic failure.
AB  - The management of each FHF patient offers valuable opportunities to learn about
      the disease process, but the severity of this illness leaves little room for
      mishaps or omissions. FHF is a true medical emergency, like cardiogenic shock or
      acute renal failure. Hepatologists and transplant surgeons should train and teach
      their team, including ICU staff and house officers, in the basic aspects of FHF
      management. Furthermore, we strongly favor the creation of "FHF groups" in
      transplantation centers frequently caring for FHF patients. This group brings
      together hepatologists, transplant surgeons, ICU staff, nurses, neurologists,
      transplant coordinators, social workers, and others to design an FHF management
      protocol, periodically update and refine it, and develop a local consensus on the
      management of the many issues surrounding the care of the patient with FHF.

PMID- 8303322
TI  - Clinical management of hepatopulmonary syndrome.

PMID- 8303323
TI  - Approach to a liver mass.

PMID- 8303324
TI  - Ethnography.

PMID- 8303325
TI  - Gender differences in occupational mobility and structure of employment in the
      British Civil Service.
AB  - In all industrialized societies health status in adults has been found to vary
      with social position. Attempts to explain this are usually grouped under headings
      of artefact, material, lifestyle and selective mobility of the healthiest. Such
      attempts have to date been unsuccessful in fully accounting for this
      relationship, and whilst they have merit have left unconsidered the effects of
      the process whereby social stratification occurs. The present study is a prelude
      to subsequent studies that will endeavour to distinguish between three separate
      influences on health--the effects of current social position, the long term
      effects stemming from one's initial class position, and the effects of the
      processes governing mobility. The purpose of our present investigation is to
      describe patterns of occupational mobility, that will enable us to identify
      possible predictors of subsequent mobility and therefore to indicate to what
      extent mobility might be a process governed by social rules. The work presented
      in this paper comprises part of the Whitehall II study of occupational, social
      and lifestyle influences upon health in a Civil Service population. Using
      multiple regression techniques almost half the variation in mobility is modelled
      in terms of educational level, fathers' social class, gender, marital status, age
      on entry into the Civil Service, length of time in Civil Service employment and
      grade of entry into the Civil Service. Using estimates derived from this model it
      is suggested that a number of sub-groups within the Civil Service suffer adverse
      mobility (mobility appears particularly restricted for women and for those
      entering the Civil Service above 30 years of age). The results obtained suggest
      that the issue of obstructed opportunity at the workplace could become a focus
      for fruitful investigation, linking issues of personal autonomy, expectations and
      control to health. A number of methodological problems in this kind of work are
      considered together with discussion of how the model can be used to increase our
      understanding of mobility.

PMID- 8303326
TI  - Judging clinical research questions: what criteria are used?
AB  - The research question is a crucial aspect of every study. Criteria for the
      evaluation of the merit of the study question or hypothesis have received
      surprisingly little attention. A set of non-methodological criteria derived from
      interviews with 40 researchers (clinical investigators and laboratory scientists)
      is presented. For both types of researcher, the terms that best described the
      nature of the criteria included potential impact, justification, feasibility,
      track record, innovation, intuitive response, aesthetics and politics. The latter
      three criteria are notably subjective; however all the criteria have an element
      of non-objectivity. There may well be a reluctance to openly acknowledge that
      crucial choices about what scientific questions should be explored involve
      criteria which are themselves not 'objective', and indeed, not even 'scientific'.

PMID- 8303327
TI  - Estimating hospital admission patterns using Medicare data.
AB  - It is often necessary in health services research and strategic planning to
      simultaneously describe the geographic pattern of admissions to multiple
      hospitals. Obtaining the data necessary to accomplish this can often be
      problematic. In some states discharge abstract data on all admissions to all
      hospitals in the state are compiled and maintained by a government agency, but in
      23 states these data are not available. Furthermore, problems arise when a
      substantial fraction of admissions cross state borders, such that data from more
      than one state is required for description of 'patient flows'. Individual
      hospitals typically maintain data on the geographic source of their own
      admissions, but are not likely to have access to such data regarding other
      hospitals in their area. Patient flow data on Medicare admissions are available
      for all states and are readily accessible, but heretofore it has not been known
      how closely the admission patterns of Medicare patients approximate those of
      other types of patients. We examine the accuracy of using data on Medicare
      admissions to estimate, at the hospital level, the admission patterns of other
      types of patients. Using zip code-to-hospital patient flow data for all non
      federal hospitals in California, we calculated the correlation between Medicare
      admission patterns and those of three other groups of patients (other adults,
      pediatrics and obstetrics) for each hospital. For the majority of hospitals,
      Medicare data predict the admissions of other adults quite well, and the
      admissions of pediatric and obstetric admissions moderately well.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8303328
TI  - Applications of O.R. in health in developing countries: a review.
AB  - In this paper, the applications of O.R. in Health in the developing countries are
      reviewed from 286 published articles spread over more than 70 periodicals,
      journals and research reports over the last two decades. The sub-areas included
      are: (a) Health Planning, (b) Disease Control, (c) Location/Allocation, (d)
      Health Administration, (e) Public Health, (f) Family Planning and (g) Nutrition
      Planning. The object of this review is to examine the extent to which O.R.
      applications in these areas are relevant to development problems of the Third
      World countries and the suitability of the existing techniques and methodologies
      for tackling such problems.

PMID- 8303329
TI  - Physician uncertainty and the art of persuasion.
AB  - Incomplete information is a chronic feature of medica markets. Much attention has
      focused on information asymmetries between physicians and their patients. In
      contrast, physician uncertainty has received far less attention. This is a
      significant omission. Physician uncertainty may be an even more important reason
      than consumer uncertainty for the high cost of health care. This paper reviews
      and evaluates major approaches for managing physician uncertainty. We argue that
      quantitative approaches alone, such as scientific advancement and the application
      of decision analysis to clinical reasoning, are insufficient for dealing with
      uncertainty. Qualitative approaches, such as forging consensus through expert
      panels, and teaching physicians to accept and cope with uncertainty, will play a
      valuable role in promoting more effective clinical decision-making under
      conditions of uncertainty. The current tensions between those who would eradicate
      physician uncertainty through quantitative approaches and those who favor
      qualitative methods has parallels in many other fields, including economics and
      mathematics. These tensions are unfortunate, since the most promising initiative
      to promote better clinical decision-making will likely need to draw upon both
      approaches. The recent initiative to implement medical practice guidelines is one
      example of a broad-based approach to improve clinical decision-making. Guidelines
      draw upon available scientific evidence, but typically involve consensus-building
      as well. They seek to persuade and educate physicians about appropriate
      treatments, without mandating changes in physician treatment patterns. Given the
      persistent uncertainties physicians will undoubtedly confront regarding
      appropriate clinical decision-making, this flexible approach may be the best way
      to mitigate market failures resulting from inappropriate clinical
      decisions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8303330
TI  - Dental care utilization over time.
AB  - Between 1950 and 1978, per capita real dental expenditures in the U.S. grew at an
      average annual rate of 3.33%. Between 1978 and 1989 there was virtually no net
      growth in this measure of dental care utilization. This sharp curtailment of
      utilization growth has promoted debate about the sources of this change. Possible
      explanations include, among others, a reduction in dental disease due to
      increased exposure to fluoridation, the substitution of noncaloric sweeteners for
      refined sugar, preventive dentistry, , improved oral health habits, an increase
      in the net price of dental services, and the cost-containment efforts of insurers
      and employers. Changes have occurred in all of these variables, but little has
      done to isolate and quantify the individual effects. This decomposition is
      difficult, in part, because of the lack of an established model for time-series
      analysis of dental care utilization. A model of dental care demand, incorporating
      economic factors (out-of-pocket or net dental prices, per capita income, and
      nondental prices) as well as dietary factors (refined sugar consumption,
      noncaloric sweeteners, and exposure to fluoridated water), is combined with a
      simple model of dental care supply within an equilibrium framework. A two-stage
      estimation procedure is applied, using U.S. aggregate time-series data for the
      period 1950-89. Results show that economic and dietary factors are significantly
      related to changes in utilization. Net price and income elasticities of demand
      exhibit the expected signs and are compatible with estimates from cross-sectional
      studies. Decreases in cane and beet sugar consumption, facilitated by the
      increase in the use of noncaloric sweeteners, are associated with reductions in
      utilization. Fluoridation appears to be weakly but positively related to
      utilization. There also appears to have been a significant structural shift in
      demand since 1978. Overall goodness-of-fit is strong and the model accurately
      tracks the 1978-89 flattening of per capita real dental expenditures. Analysis of
      the relative contribution of each independent variable suggests that economic,
      dietary, and structural shift factors have contributed to this curtailment of
      growth.

PMID- 8303332
TI  - Coping with the Gulf war: subculture differences among ischemic heart disease
      patients in Israel.
AB  - The purpose of this study was to assess short term effects of the Gulf war on
      ischemic heart disease patients of different ethnic origin. Three dimensions of
      patients' reactions to the war situation were studied: psychological, physical
      and behavioral. The study first focused on changes in patients' responses on
      these dimensions over three stages of the war, differentiated according to degree
      of threat. Second, differences stemming from ethnic origin were examined among
      patients who live in the same geographical region, use the same health services
      and were exposed to the same threatening life event. One hundred ischemic heart
      disease patients were interviewed while waiting in outpatient hospital clinics
      for a regular examination at the end of the war. The results of intrapersonal
      comparisons showed that the intensity of responses, as expected, increased
      significantly on the three dimensions from the week before the war started to the
      first week of the war, which was the most stressful period for Israelis. During
      the last week of the war, however, when stress was significantly reduced, the
      expected change was found primarily with regard to psychologic responses. That
      is, worries were significantly reduced, but no significant reduction in frequency
      of anginal pain and in drug consumption followed, indicating differences in the
      adjustment process on the psychologic and physical levels. Subcultural
      differences were found in the studied responses: Patients of Asian or North
      African countries of origin reported having more frequent anginal pains, and
      consuming more drugs than patients from Western countries.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8303331
TI  - Formulating selection policies for assisted reproduction.
AB  - This paper addresses one of the most important problems in the area of assisted
      reproduction, namely the selection policies used by the providers of the
      services. Some of the difficulties involved in formulating policies in this area
      are outlined. The paper concludes that public involvement in decision making in
      this area is vital, and that to facilitate this the issues must be opened up to
      public scrutiny and debate. Such a debate would be a significant first step
      towards the implementation of policies which reflect the opinion of the entire
      community rather than just the professionals who provide the service, or
      sectional groups who manage to influence the professionals.

PMID- 8303333
TI  - International migration and control of communicable diseases.
AB  - The epidemiology and policy implications of communicable disease (CD)
      transmission associated with international migration have received little
      systematic study. This is a review of clinical and epidemiological reports in
      search of strategies to assess and manage the impact of international migration
      on the transmission of CDs. The economics and demography of migration from less
      developed to industrialized nations is considered. Migration-related transmission
      should differentiate between actual transmission as opposed to geographic
      relocation of disease. Limitations of current screening and disease prevention
      strategies are discussed. Social and ecological processes through which migration
      can contribute to increased CD transmission are described, including placement in
      refugee camps, unclear legal status of migrants in recipient nations, and
      temporary return migration. Strategies for non-discriminatory and non-punitive
      control of migration-related CDs, needed changes in clinical practice, and
      complexities presented by CDs of long latency (such as HIV infection) are
      reviewed.

PMID- 8303334
TI  - Accessibility of dental services according to family income in a non-insured
      population.
AB  - The aim of this study was to examine the effect of family income on accessibility
      to dental services among adults in Norway. The analysis was performed on a set of
      national data collected in 1989, which was representative of the non
      institutionalized Norwegian population aged 20 years and above. The sample size
      was 1200 individuals. The data were analyzed according to a two-part model. The
      first part determined the probability of whether the consumer had demanded the
      services or not during the last year according to family income. The second part
      estimated how the amount of services utilized depended on family income, for
      those with demand. The elasticity of the odds of having demanded the services
      with respect to family income was 0.48. Family income had no effect on the amount
      of services utilized. Additional analyses also showed that there was no effect of
      family income on the probability of having received a filling or a crown when
      visiting the dentist. In Norway, almost all costs for dental services are paid by
      the consumer. It is not possible from the data alone to say whether subsidized
      dental care is an effective way of reducing the inequalities in demand.

PMID- 8303335
TI  - A comparison of social support and social networks of black parents and white
      parents with chronically ill children.
AB  - Characteristics of social networks and provision of support were examined for two
      groups of parents of chronically ill children, one group black and one group
      white. Black and white parents both reported similarities in the experience of
      parenting a child with a chronic illness. Both sets of parents relied primarily
      on family networks to provide much needed support. White networks were twice as
      large as black networks, although black parents perceived the individuals in
      their networks as being more supportive. For both groups, the networks were of
      long duration. Network members were geographically closer to blacks. White
      parents discussed support mostly in terms of affect. Black parents described
      support as instrumental actions. Differences in income levels between blacks and
      whites might account for differing descriptions of support. The experience of
      having a chronically ill child appears to override racism in the health care
      system. Black parents did not perceive any problems, based on race, that affected
      receiving medical care for their children.

PMID- 8303336
TI  - The Ray Alexander Workers Clinic--a model for worker-based health services in
      South Africa?
AB  - During the period of current political transition, concern for the future of
      South Africa's health services have led to increased interest in different models
      for the provision and financing of health care. These debates have included an
      examination of the concept of Managed Care and the ideas of Health Maintainance
      Organization. Progressive trade unions, particularly, have been faced with the
      prospect of promoting private sector health care if they are directly to meet
      their members health needs, while at the same time seeking an equitable health
      care system for a future democratic South Africa. The Ray Alexander Workers
      Clinic is presented as a model of a worker-based health service which attempts to
      address this contradiction. Important lessons for a future National Health
      Service may be learnt. The role of worker control and cost containment are
      emphasized and implications for integration into State Services and relationships
      to social services for the broader community are explored. An argument is made
      that worker-based health services offer excellent possibilities for integration
      in a future National Health Service in South Africa that is centred on a Primary
      Health Care approach.

PMID- 8303337
TI  - Development and consequences of group living in Sweden. A new mode of care for
      the demented elderly.
AB  - The process of developing a new mode of care for the demented elderly, group
      living (GL), is evaluated and the consequences discussed. The increasing
      proportion of very old persons in Sweden means a higher prevalence of dementia.
      The majority of patients in traditional institutional long term care show
      cognitive deterioration. An insufficient caring situation, both in quantity and
      quality has long been observed. This, and a better knowledge and understanding of
      dementing diseases, their symptoms and consequences, has been the impetus to
      develop an alternative care model, group living (GL), for well defined groups of
      demented elderly. The concept of GL discussed here means a setting strictly
      adapted to the abilities and psychosocial needs of moderately diseased Alzheimer
      and vascular demented patients. Security, integrity promoting therapy and
      activation are specially stressed. The importance of informing and educating
      different kinds of actors simultaneously to structural changes in social and
      physical patterns within the implementation of the new concept is illustrated.

PMID- 8303338
TI  - Evaluation of AIDS prevention among homosexual and bisexual men in Switzerland.
AB  - Attitudinal and behavioural change among gay men in Switzerland was measured
      between 1987 and 1990 to evaluate the effectiveness of AIDS prevention
      activities. The methodology used included a self-administered questionnaire
      published in Swiss gay magazines and distributed by gay organizations (N = 795 in
      1987, N = 720 in 1990) and in-depth interviews with men recruited through
      advertisements and through the questionnaire (N = 42 in 1987, N = 24 in 1990).
      The two independent sampling procedures yielded similar samples with regard to
      socio-demographic characteristics, allowing comparisons to be made between the
      1987 and 1990 data. Personal confrontation with AIDS (knowing someone who is HIV
      positive, or who is ill or dead from AIDS) increased significantly during the
      period but more adequate ways of coping developed. Behavioural change towards
      safer sex began well before the first study. The majority of responding
      homosexuals have adapted their sexual behaviour to the new situation created by
      AIDS and generally maintain a protective behaviour. However, "exceptions" (condom
      rupture or episodes of non-protection) are not infrequent and should deserve more
      attention. Three indicators of sexual behaviour (number of sexual partners, anal
      sex and use of condom and oral sex with ejaculation), reported for the last 3
      months before each study, exhibit few changes between 1987 and 1990: number of
      partners remained stable, unprotected oral sex decreased. Anal sex slightly
      increased, the use of condoms remaining stable. Sixty-seven percent of the sample
      knew their serostatus in 1990 (57% in 1987), and 13% of these stated that they
      were HIV+ (14% in 1987).

PMID- 8303339
TI  - Life events, chronic difficulties and vulnerability factors preceding breast
      cancer.
AB  - This study deals with the association between life events, family history of
      mammary carcinoma and breast cancer. It was guided by a model consisting of
      events, family disposition and age at the side of the independent variables. In
      addition to these factors 'lack of social support' was introduced. The latter is
      conceptualized as a vulnerability factor capable of aggravating the impact of
      events without having an independent effect. There was no hypothesis on chronic
      difficulties, so this is exploratory. This research was conducted as a so-called
      'limited prospective' design. Women with a suspicious breast lump were
      interviewed before surgery. After having confirmed the outcome of the surgery the
      sample was divided into a group with cancer and cases with a benign diagnosis.
      Women with gall stones were introduced as another control group. The interviews
      were performed along a semi-structured schedule, tape recorded and analyzed by
      using Brown and Harris' Life Events and Difficulties Scale. The analyses were
      made with 33 women with cancer, 59 with a benign tumor and 20 with gall stones.
      In the 'malignant' group the severest events was four times as high as in
      controls. All other degrees of threat were equally distributed over the groups.
      Chronic difficulties of the highest degree of severity also occur more often in
      the cancer group. They are not independent from events so that analyzing them
      separately is not useful. The rate of family history of breast cancer does not
      differ between the tumor groups, but is much lower in the gall stone patients. In
      the cancer group there is an association between this possibly hereditary factor
      and severe events, in the 'benign' group both are uncorrelated. The life event
      effect is explained in context of a higher illness susceptibility due to a
      hereditary disposition. For events occurring without it an explanation remains
      unclear.

PMID- 8303340
TI  - Not worth the risk? Attitudes of adults with learning difficulties, and their
      informal and formal carers to the hazards of everyday life.
AB  - Twenty adults with learning difficulties (adults) living at home with informal
      carers, mostly parents, and attending Adult Training Centres (ATCs) were
      interviewed about their everyday lives and information was also obtained from
      informal and formal carers. The problem of dealing with the hazards of everyday
      life emerged as an important theme. The thinking of adults and informal carers
      could be understood in terms of the moral dimension of hazards, through the
      distinction between risks, to be calculated, and dangers, to be avoided. Adults
      and informal carers within families largely agreed in their categorization of
      hazards but differences were found. In families where the head of the household
      had had a professional or skilled manual occupation, adults and informal carers
      were most likely to agree that hazards for the adult were dangers to be avoided.
      In families which had a history of unemployment or unskilled occupations, adults
      and informal carers were most likely to treat certain hazards as risks to be
      taken. The latter families were also less likely to have 2 informal carers.
      Adults from more risk-tolerant families appeared to be achieving more of their
      potential in everyday living skills. Formal carers at ATCs were more accepting of
      risks for adults with learning difficulties than informal carers and there was
      misunderstanding and conflict between formal and informal carers as a result.

PMID- 8303342
TI  - Community health promotion programs.

PMID- 8303341
TI  - Growth monitoring and the promotion of breastfeeding.
AB  - Recent studies evaluating the efficacy of growth monitoring programs have
      scrutinized their educational and preventive capabilities. Advocates claim that
      growth monitoring can be effective if communities and mothers are more actively
      involved in the process of weighing and measuring, and if the technology is
      understood by all as an aid for disease prevention and health promotion rather
      than as a 'curative' procedure. Others have argued that this theory is rarely
      possible to implement. The ways in which preventive growth monitoring can be made
      possible are still under exploration, given that the reasons for such deeply
      imbedded 'curative' expectations of growth monitoring are not fully understood.
      Any such understanding requires an analysis of growth monitoring within the
      context of the GOBI (growth monitoring, oral rehydration therapy, breastfeeding
      and immunization) child survival framework. To attain this type of understanding,
      a series of qualitative methodological techniques were used in a population of 50
      mothers and several health care facilities in Pelotas, RS, Brazil, as a
      complement to pre-existing epidemiological data from the Center for Epidemiology
      at the Federal University of Pelotas. With a subsample of 15 mothers, intensive
      interviews and observations were specifically focused on: (1) mothers'
      understanding of growth monitoring, (2) breastfeeding practices and beliefs, (3)
      doctor-patient communication. Findings from this study suggest that, even in a
      program with widespread attendance and a relatively 'interactive' growth
      monitoring approach, the use of growth charts do little to promote duration or
      frequency of breastfeeding, and may even pay a role in the factors which deter
      women from choosing to breastfeed for longer durations or with greater frequency.
      We found that mothers' personal interpretations of the charts were representative
      of the larger socio-cultural and economic issues that affected their lives on a
      daily basis. Growth charts thus served as one of the many tangible domains onto
      which mothers could project their worries and measure their personal 'successes'
      and 'failures'.

PMID- 8303343
TI  - Primary mental health care in Nicaragua five years later.

PMID- 8303344
TI  - [Evaluation of pain in a cancer patient].

PMID- 8303345
TI  - [Postoperative pain and analgesic techniques in the adult].

PMID- 8303346
TI  - [Painful chronic syndrome and depression].

PMID- 8303347
TI  - [Pain at home].

PMID- 8303348
TI  - [Pain at night in oncologic surgery].

PMID- 8303349
TI  - [Pain and kinesitherapy].

PMID- 8303350
TI  - [Pain in danger].

PMID- 8303352
TI  - [Relaxation].

PMID- 8303351
TI  - [Pain treatment and dietetics].

PMID- 8303353
TI  - [Plan for the education of a patient, treated with oral morphine].

PMID- 8303354
TI  - [Physiology of pain].

PMID- 8303355
TI  - [Around Christmas 1989].

PMID- 8303356
TI  - [Chantal Clout-Billard, industrial health counselor. Interview by Francoise
      Henin].

PMID- 8303357
TI  - [Second edition of the International Nursing Film Festival].

PMID- 8303358
TI  - [Quinidine].

PMID- 8303359
TI  - [Placing a gastric probe].

PMID- 8303360
TI  - [Nursing of comatose patients].

PMID- 8303362
TI  - [Elimination].

PMID- 8303361
TI  - [Feeding of unconscious patients and of patients about to awaken].

PMID- 8303363
TI  - [Tracheotomy].

PMID- 8303364
TI  - [Relations with the patient during coma and in the phase of awakening].

PMID- 8303365
TI  - [Spiritual charge of patients with head injuries].

PMID- 8303366
TI  - [The work load in a unit of patients in a chronically vegetative state].

PMID- 8303367
TI  - [Therapeutic monitoring].

PMID- 8303369
TI  - [Movement therapy].

PMID- 8303368
TI  - [Relationships with the families].

PMID- 8303370
TI  - [Coma and the vegetative states].

PMID- 8303371
TI  - [Rehabilitation of brain-damaged patients. Ergotherapy].

PMID- 8303372
TI  - [Caring for aphasic, brain-damaged patients].

PMID- 8303373
TI  - [Psychological intervention].

PMID- 8303374
TI  - [Legal protection of patients in coma].

PMID- 8303375
TI  - [Institutionalization of brain-damaged patients].

PMID- 8303376
TI  - [The return home].

PMID- 8303377
TI  - [Professional rehabilitation of patients with brain injuries].

PMID- 8303378
TI  - [The Regional Hospital and University Center of Caen and the history of
      hospitalization in Caen].

PMID- 8303379
TI  - [Taking charge of psychiatric emergencies].

PMID- 8303380
TI  - [Modalities in the admission of patients with mental disorders].

PMID- 8303381
TI  - [Organization of the taking-over of patients in Paris psychiatric emergency
      services].

PMID- 8303382
TI  - [Suicide].

PMID- 8303383
TI  - [Mental confusion].

PMID- 8303384
TI  - [Liaison psychiatry and diabetology].

PMID- 8303385
TI  - [Psychiatric emergency drugs].

PMID- 8303386
TI  - [Nursing observation and monitoring].

PMID- 8303387
TI  - [Blowing on the crisis].

PMID- 8303388
TI  - [Functions of the social worker in the psychiatry service].

PMID- 8303389
TI  - [After the crisis or emergency period].

PMID- 8303390
TI  - [The place of psychiatry in forensic emergencies at Hotel-Dieu].

PMID- 8303391
TI  - [Nursing care at Salle Cusco].

PMID- 8303392
TI  - [Oxygen therapy].

PMID- 8303393
TI  - [Germs responsible for nosocomial infections].

PMID- 8303394
TI  - [Monitoring nosocomial infections].

PMID- 8303395
TI  - [Practical organization of the fight against nosocomial infections].

PMID- 8303396
TI  - [Suggestion for a method of following-up nosocomial infections and results of a
      study of their incidence].

PMID- 8303397
TI  - [The impact of cytotoxic chemotherapy from the viewpoint of patients, specialists
      and nurses].

PMID- 8303398
TI  - [Did you say hygiene?].

PMID- 8303399
TI  - [Behavioral interventions and psychological aspects of care during chemotherapy].

PMID- 8303400
TI  - [The Hotel-Dieu in Paris. From its founding to the middle of the 20th century].

PMID- 8303401
TI  - [Nursing diagnosis: its realities].

PMID- 8303402
TI  - [Good day, pain].

PMID- 8303403
TI  - [Important reforms].

PMID- 8303404
TI  - [Administration of insulin].

PMID- 8303405
TI  - [Sympathomimetic amines].

PMID- 8303406
TI  - [Nosocomial infections. Definitions and epidemiological aspects].

PMID- 8303407
TI  - [Parkinson disease: therapy].

PMID- 8303408
TI  - [Parkinson disease: unusual treatments and perspectives].

PMID- 8303409
TI  - [Parkinson disease: nursing care].

PMID- 8303410
TI  - [Injections of apomorphine: educational projects].

PMID- 8303411
TI  - [Functional rehabilitation in Parkinson disease].

PMID- 8303412
TI  - [Parkinson's disease: principal signs and natural development].

PMID- 8303413
TI  - [Living with Parkinson disease].

PMID- 8303414
TI  - [The French Parkinson Association].

PMID- 8303415
TI  - [Nicole Benevise: the eyes on care].

PMID- 8303416
TI  - [Health in the comic strips].

PMID- 8303417
TI  - [How to make mental disease better known, understood and accepted].

PMID- 8303419
TI  - [Electrocardiography: how to get a good recording].

PMID- 8303418
TI  - [Inhibitors of the proton pump].

PMID- 8303420
TI  - [Parkinson's disease: modern evolution].

PMID- 8303421
TI  - [Epidemiology, prevention and organization of care].

PMID- 8303422
TI  - [Taking emergency charge of a burn patient].

PMID- 8303423
TI  - [Everyday life of a nurse in a center for the severely burned].

PMID- 8303424
TI  - [Follow-up of burns in outside consultation].

PMID- 8303425
TI  - [Burns: general aspects, principles of treatment].

PMID- 8303426
TI  - [The rehabilitation of the burn patient: from cicatrization to rehabilitation].

PMID- 8303427
TI  - [Taking charge of burn patients. Some psychological aspects].

PMID- 8303429
TI  - [The patient and his nutrition during bone marrow transplantation].

PMID- 8303428
TI  - [Role of the social service in a burn center].

PMID- 8303430
TI  - [Taking charge of cancer patients. The role of information].

PMID- 8303431
TI  - [The painful act of puncture in pediatric hemato-oncology. Nursing experience of
      introducing an analgesic protocol].

PMID- 8303432
TI  - [In memory of Simone Chaze 1 October 1940-1 June 1993].

PMID- 8303433
TI  - [The tetracyclines].

PMID- 8303434
TI  - [Capillary blood collection for blood gas analysis].

PMID- 8303435
TI  - Cervical spine surgery in rheumatoid arthritis: improvement of neurologic deficit
      after cervical spine fusion.
AB  - Ninety of 110 consecutive patients with rheumatoid deformities of the cervical
      spine surgically treated had associated neurologic deficits. Fifty-five patients
      had atlantoaxial subluxation. In this group, there were 16 Ranawat Class I
      patients (normal), 21 Class II (weakness, hyperreflexia, dysesthesia), 13 Class
      IIIA (paresis and long-tract findings but can ambulate), and five Class IIIB
      (quadriparesis and inability to ambulate). After C1-C2 stabilization, 94.8%
      improved at least one class. Twenty-two patients had AAS-SMO (atlanto-axial
      subluxation and superior migration of the odontoid) only one before surgery was
      Class I, five Class II, eight Class IIIA, and eight Class IIIB. Seventy-six
      percent improved at least one class after surgery. Nineteen had isolated subaxial
      subluxation (SAS). Three were Class I, two Class II, nine Class IIIA, and five
      were Class IIIB. After surgery, 94% improved at least one class, and all were
      ambulating. Fourteen had combined AAS-SMO-SAS deformities. There were no Class I
      patients, only four Class II, four Class IIIA, and six Class IIIB. After surgery,
      71% improved. The four deaths that occurred in the immediate postoperative period
      were Class IIIB. Fifteen patients had worsening or recurrence of their symptoms.
      Thirteen of these were related to the later development of subaxial subluxation.
      Neurologic symptoms and recovery were related to severity of the deformity. Those
      with SMO had greater neurologic deficits and worse results. In general,
      neurologic recovery is encouraging even in the IIIB patient. Earlier surgery
      should be done, however, particularly before SMO develops, if possible.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8303436
TI  - The outcome of pseudarthrosis after cervical anterior fusion.
AB  - This article reviews the outcome of 23 consecutive patients who developed
      pseudarthrosis after anterior cervical fusion surgery. Sixteen of the 23 patients
      failed to achieve significant relief of their symptoms (69.6%). These 16 had a
      second fusion procedure. Thirteen of this same 16 obtained a fusion, and 9 of
      these (69.2%) converted to an excellent or good result. These findings support
      the thesis that solid arthrodesis is important to a successful outcome of
      anterior cervical fusion procedures.

PMID- 8303437
TI  - A comparative study of fixation techniques for type II fractures of the odontoid
      process.
AB  - Primary screw fixation of a Type II odontoid fracture or non-union is an
      attractive alternative to posterior atlanto-axial arthrodesis in that normal
      cervical motion can be maintained. Eight cervical cadaver spines, ranging in age
      from 17-90 years, were used for study. Type II fractures of the dens were created
      using an osteotome. Simulated fractures were fixed using one or two 3.5-mm bone
      screws. After testing each screw fixation technique, the screws were removed and
      a posterior C1-C2 brooks sublaminar wiring was performed using four 18-gauge
      wires with wooden blocks to simulate bone graft. No significant differences were
      found between bending and torsional stiffnesses for the one-screw and two-screw
      specimens. No significant differences were found between one- and two-screw
      fixation when compared with primary C1-C2 wiring in torsion. One- or two-screw
      fixation was as stiff as primary C1-C2 wiring in bending. One or two screws
      offers similar stability for fixation for a dens fracture. One- and two-screw
      fixation is at least as stiff as primary C1-C2 wiring in torsion and one- or two
      screw fixation is stiffer than primary C1-C2 wiring in bending.

PMID- 8303438
TI  - Three-dimensional motion analysis of the upper cervical spine during axial
      rotation.
AB  - Rotational motion of the normal upper cervical spine was analyzed in 20 men using
      biplanar roentgenograms, a system digitizer, and a personal computer. To detect
      the bony landmarks of the atlas, the subjects' heads were fixed and their trunks
      rotated in the reference frame while these biplanar studies were obtained.
      Coupling motions observed included 10 degrees extension at C0-C1, with 11 degrees
      of lateral bending between C1-C2. Almost all (80%) cervical axial rotation took
      place at C1-C2, whereas only 4 degrees of rotation occurred at C0-C1.
      Furthermore, as C1-C2 axial rotation increased, so did rotation in the opposite
      direction at C0-C1 while less rotation was noted below C2. The instantaneous axis
      of rotation was located anterior to the foramen magnum at the C0-C1 level, in the
      central portion of the dens at C1-C2.

PMID- 8303439
TI  - Interspace distraction and graft subsidence after anterior lumbar fusion with
      femoral strut allograft.
AB  - The authors performed a retrospective review of 32 patients who had undergone a
      single-level anterior lumbar fusion with femoral strut allograft as an isolated
      procedure. The goal of the study was to use clinical radiographs to measure
      interspace distraction, graft subsidence, interspace collapse, the nature of
      allograft incorporation, and to correlate these results with successful
      arthrodesis. Results were categorized according to plain radiographic appearance
      and flexion/extension stability. Sixty-six percent of the group exhibited
      radiographic union with flexion/extension stability. Twenty-two percent exhibited
      stability on the flexion-extension analysis but less than complete arthrodesis
      was present. Twelve percent exhibited radiographic non-union and flexion
      extension instability. Interspace distraction of 11 mm was obtained initially
      with a follow-up distraction of 5.5 mm. Graft subsidence was noted posteriorly in
      27 patients with an average subsidence of 4 mm. The authors' conclusions were: 1)
      Interspace distraction can be achieved with anterior lumbar fusion if appropriate
      interbody grafts are used. 2) Despite a solid arthrodesis rate of only 66%,
      "functional arthrodesis" was achieved in 88%. In a retrospective review of
      patients who underwent anterior lumbar fusion with femoral strut allograft,
      interspace distraction, graft subsidence, and incorporation and arthrodesis
      status were measured. A solid arthrodesis was achieved in 66% of the patients,
      and functional arthrodesis in another 22%. Interspace distraction was maintained
      in 59% of cases.

PMID- 8303441
TI  - Morphologic variation of lumbar posterior longitudinal ligament and the modality
      of disc herniation.
AB  - The authors investigated the relationship between the type of lumbar disc
      herniation (471 discs) and the gross anatomy of the posterior longitudinal
      ligament (PLL) in the lumbar region of 10 cadavers. The size of PLL diminished
      significantly as the disc level became lower (P < 0.00001), and there are loose
      attachment of the central area of rhomboidal expansion of PLL. In the upper
      lumbar region, central or central-lateral herniation with an intact PLL was
      predominant. The type of disc herniation appeared to be influenced by the width
      and development of the PLL with a loosely connected central area. In the lower
      lumbar region, posterior-lateral extrusion with a ruptured PLL was predominant.
      This may be related to the small or poorly developed PLL in lower
      lumbar/lumbosacral region. It is suggested that the type of disc herniation (PLL
      intact or ruptured) is related to the morphologic variation of PLL.

PMID- 8303440
TI  - The use of dermatomal evoked responses during surgical procedures that use
      intrapedicular fixation of the lumbosacral spine.
AB  - Monitoring of electrophysiologic function during intrapedicular fixation of the
      lumbosacral spine can be useful because this fixation technique has been
      associated with a significant number of postoperative radicular complications.
      Somatosensory evoked potentials (SEPs) traditionally have been used to monitor
      neurologic function during spinal instrumentation procedures. A case is presented
      of an intrapedicular fixation procedure that was monitored with SEPs and that
      resulted in false-negative SEP findings. This result suggests that SEPs may not
      be a sensitive enough monitoring tool for detecting compromise of single root
      function, and as a result, other monitoring techniques should be used. Dermatomal
      somatosensory evoked potentials (DSEPs) have been reported to be useful in this
      regard. To test their usefulness, 81 lumbosacral intrapedicular fixation
      procedures were monitored with DSEPs. Repeatable responses were obtained from all
      but one of the patients. The responses were sensitive to the compromise of root
      function. Predictions of postoperative outcome were dependent only on the
      responses at closing and not on changes that occurred during surgery.

PMID- 8303442
TI  - Clinical effectiveness of behavioral signs for screening chronic low-back pain
      patients in a work-oriented physical rehabilitation program.
AB  - This prospective study investigated the relationship between behavioral sign
      scores (from Waddell) and the return to work status of chronic low-back pain
      patients who completed a work-oriented physical rehabilitation program without
      formal facility-related psychologic or social services. Further, the authors
      monitored the effect of this program on changing these scores. The program
      consisted of physical reconditioning through resistive exercises, flexibility and
      aerobic training, posture and body mechanics education, and progressive work
      simulation tasks and activities of daily living. One hundred eighty-three
      nonworking or partially disabled low-back pain patients with an average duration
      of 8.7 months' disability were included in the study. The presence of each of
      eight behavioral signs was tested for on entry and again on completion of the
      program. Analysis showed a significant drop in behavioral sign scores for
      patients who successfully returned to work. There was no significant reduction in
      scores for patients who did not return to work. The results suggest these signs
      may predict the effectiveness of treating chronic low-back pain patients in a
      return-to-work physical rehabilitation program. Conversely, screening for
      behavioral signs may identify low-back pain patients who would benefit from
      intensive behavioral and psychiatric testing and intervention efforts.

PMID- 8303443
TI  - Diabetic lumbar radiculopathy: sciatica without disc herniation.
AB  - Three patients with diabetic radiculopathy (DR) are presented. The clinical
      aspects of DR, its management, and differential diagnosis are reviewed. Diabetic
      radiculopathy commonly presents with severe unilateral pain of sudden onset that
      is usually located in the lower extremity, frequently in the proximal segments.
      Occasionally, bilateral asymmetric pain may be observed. The pain is severe and
      may require narcotic medications. Sphincteric involvement is rare. Weakness of
      hip or thigh muscles, decreased sensation and hypo- or areflexia are commonly
      observed. The clinical picture can resemble that of high lumbar disc herniation.
      Electrodiagnostic and radiological studies may help differentiate between the two
      conditions.

PMID- 8303444
TI  - Effects of anterior vertebral grafting on the traumatized lumbar spine after
      pedicle screw-plate fixation.
AB  - This study was conducted to determine the effects of corpectomy and anterior
      strut grafting on the biomechanics of traumatized lumbar spine after pedicle
      screw-plate fixation. Eight lumbar spines were loaded until fracture (initial
      cycle) and then reloaded to the same deformation (injury cycle). After
      transpedicular fixation, spines were again loaded (fixation cycle). Partial
      corpectomy of the fractured body and anterior strut grafting were accomplished;
      the spine reloaded (strut cycle). Spine angles were measured and biomechanical
      strength and kinematic parameters analyzed. Load-deformation relationships were
      similar for fixation and strut cycles until maximum load; at failure, loads were
      higher for the former (P < 0.05), however. Alignment was improved by
      stabilization or stabilization plus anterior grafting (P < 0.05). Vertebral
      height was best maintained by grafting as an adjunct to pedicle fixation (P <
      0.05). Kinematics were largely unaffected by grafting, except for reduced motion
      at the posterior vertebral targets between the fixated levels (P < 0.05). The
      strength of the fixated spine is relatively unchanged by corpectomy and anterior
      grafting; alignment may be improved in the latter group.

PMID- 8303445
TI  - Functional radiographs of acute thoracolumbar burst fractures. A biomechanical
      study.
AB  - The geometric changes of acute thoracolumbar burst fractures under extension and
      traction loadings were analyzed using functional radiographs. The injuries were
      produced in an in vitro high-speed impact model. The changes in nine geometric
      parameters (three angular and six linear) were analyzed from neutral posture to
      extension and traction positions. In the extended position, all parameters,
      except the posterior vertebral height and vertebral diameter, were significantly
      different from the neutral posture values. Also in extension, the posterior
      vertebral height, vertebral diameter, and posterior unit height were
      significantly different from their intact values. In the traction position, all
      nine geometric parameters changed significantly from the neutral posture, whereas
      only the vertebral diameter remained significantly different from its intact
      value. These findings demonstrated the treatment advantages of applying traction
      force to acute burst fractures in contrast to extension moments. Further, changes
      in the angular parameters due to motion from neutral to extension posture
      demonstrated that the acute flexibility of the three-vertebrae segment was
      contributed almost equally by the upper disc (35%), lower disc (27%), and
      fractured vertebra (38%).

PMID- 8303446
TI  - Caudo-cephalad loading of pedicle screws: mechanisms of loosening and methods of
      augmentation.
AB  - The mechanism of failure and the effect of augmentation of single pedicle screws
      subjected to caudo-cephalad loads applied at the screw head were investigated. In
      each of 10 lumbar vertebrae, Steffee pedicle screws of appropriate diameter were
      placed in one pedicle. The cancellous bone of the contralateral pedicle was
      removed by curettage, a custom fabricated bushing was pressed by hand into the
      space, and a Steffee screw was inserted through the bushing and into the
      vertebral body. This arrangement was designed to transfer load directly from the
      pedicle screw to cortex, bypassing the cancellous bone of the pedicle. In a
      second experiment, a custom plate was mounted to the posterior surfaces of the
      articular facets allowing load transfer from the head of the screw directly to
      cortex. Caudo-cephalad loads were applied by a materials tester and toggle
      displacement (defined as the total caudo-cephalad movement of the screw under
      minimal load after loading through a complete cycle) was measured. Under peak
      loads of +199 N (caudal) and -224 N (cephalad), mean toggle at the screw head was
      4.93 mm (standard deviation [SD] = 3.60 mm) for the screw alone and 4.96 mm (SD =
      4.42 mm) for the screw augmented by the bushing. Screws without augmentation
      showed a characteristic pattern of loosening with the base of the pedicle acting
      as a fulcrum and a butterfly-shape void occurring in the vertebra and the pedicle
      where cancellous bone had been crushed. Problems with the bushing included poor
      fit, back-out, and split pedicles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8303447
TI  - Surgical and clinical results of scoliosis surgery using Zielke instrumentation.
AB  - All patients with idiopathic thoracolumbar or lumbar scoliosis treated by a
      single surgeon with a single-stage fusion with Zielke instrumentation and a
      minimum 2-year follow-up were reviewed. Thirty-two patients were reviewed (94%
      follow-up), 13 adolescents and 19 adults. All patients were evaluated clinically
      and radiographically, as well as psychosocially. There were no major
      complications. The average curve correction was 73%. The instrumentation was
      kyphogenic, but this did not affect the overall sagittal contour or the clinical
      results. Back pain was significantly improved, as was cosmesis. The Zielke device
      was found to be an effective device for the correction of thoracolumbar and
      lumbar curves in selected adolescents and adults.

PMID- 8303448
TI  - The use of Texas Scottish-Rite instrumentation in idiopathic scoliosis. A
      preliminary report.
AB  - The Texas Scottish-Rite instrumentation (TSRH) is a new system for the correction
      of spinal deformities that uses smooth rods and hooks stabilized to the rod with
      a three-point interference fit. This obviates the need for the break-off hex
      bolts and should make for easier removal and/or revision. Twenty-three patients
      with TSRH instrumentation were followed for an average of 18 months after
      surgery. The major scoliotic curve was corrected an average of 49% with the
      compensatory curve averaging 37% correction. Loss of thoracic kyphosis was less
      than 9 degrees although it increased on average 8 degrees in those patients where
      kyphosis was improved. There were no acute complications, but late complications
      included four cases of hook pull-out. Results are comparable to those found with
      the CD instrumentation. The TSRH instrumentation is an attractive alternative in
      scoliosis surgery, particularly because of the relative ease in which revision
      surgery may be performed.

PMID- 8303449
TI  - Three-dimensional simulation of Harrington distraction instrumentation for
      surgical correction of scoliosis.
AB  - Harrington distraction rod surgery on six female patients with idiopathic
      scoliosis was simulated in three-dimensional osseoligamentous finite element
      models with individual geometry taken from preoperative stereo roentgenographic
      reconstructions of the spine and ribcage and compared with the measured outcome.
      Boundary conditions at the ends of the spine were used to maintain pelvis and
      head alignment. Published material and flexibility properties were used. The
      amount of hook distraction was calculated from measured changes in the distance
      between the hook sites (range, 13-27 mm). Initial simulations underestimated the
      Cobb angle correction by an average 6%. They underestimated the spinal elongation
      by 36% and predicted an average 12 degrees increase in kyphosis angle compared
      with an actual 10 degrees average decrease. Agreement for sagittal plane changes
      improved in five cases when the beams representing the motion segments were
      displaced posteriorly. In the sixth case (with the rod applied over a lordotic
      spinal region), agreement was improved with the motion segment beams displaced
      anteriorly. The amount of the beam displacement that gave the best agreement was
      variable, and we were not able to predict it for each individual. Both measured
      and simulated changes in vertebral transverse plane rotations and in rib
      angulations were small. The greatest source of errors in these simulations
      appeared to be inadequate representation of in vivo motion segment behavior by in
      vitro measured stiffness properties.

PMID- 8303450
TI  - Sacral screw loads in lumbosacral fixation for spinal deformity.
AB  - Fixation to the sacrum and pelvis is a problem in the operative treatment of
      spinal deformity. Previous testing of pedicle screws address axial pull-out
      strength, yet how screws are loaded in vivo remains unknown. The goals of this
      study were to determine the loads experienced by sacral screws when loaded as
      part of Cotrel-Dubousset (CD) sacral instrumentation and whether different
      anterior grafting methods would effect screw loads. Sacral screws were modified
      to become transducers capable of measuring axial and bending loads. The screw
      transducers were incorporated into the sacral fixation of CD instrumentation in
      seven calf spines. Specimens were loaded to simulate flexion. The sacral screws
      carried axial loads (1.1 N/[Nm of load]) and bending moments (1.1 Nm/[Nm of
      load]). The results suggest bending of the sacral screws may be important in
      their failure, and screw loading was not dependent on graft types used.

PMID- 8303451
TI  - The effects of immobilization of long segments of the spine on the adjacent and
      distal facet force and lumbosacral motion.
AB  - Long levels of spinal instrumentation and fusion are common in surgery for spinal
      deformity. The effect on the remaining mobile segments is not well understood.
      The changes in lumbar facet loading and lumbosacral motion were evaluated as the
      number of immobilized levels increased. Four fresh canine cadaveric spines from
      T6 to sacrum were used. Lumbosacral motion was measured with an instrumented
      spatial linkage device, and facet loads were measured at L1, L4, and L7 using a
      strain gauge technique. Lumbosacral motion and facet loading were significantly
      increased (P < 0.05) after immobilization of proximal segments, and the amount of
      the increase was dependent on the number of immobilized segments (P < 0.05). This
      indicates that immobilization of long segments of the spine influences the
      remaining mobile segments by increasing the load and motion not only at the
      immediately adjacent segment but also at the distal segments.

PMID- 8303452
TI  - Isometric maximal and submaximal trunk extension at different flexed positions in
      standing. Triaxial torque output and EMG.
AB  - Thirty-one healthy men were tested for the effects of trunk-flexion positions (0
      degrees, 15 degrees, and 35 degrees) in standing on triaxial torques and
      electromyogram of 10 trunk muscles during voluntary maximal and submaximal
      isometric trunk extension. At a more flexed position, both erector spinae and
      latissimus dorsi showed significantly higher RMS-EMG. The abdominal obliques were
      coactivated only during 100% maximum voluntary exertion at each posture. In all
      tests, the rectus abdomini were quiet. Mean maximum extension torque increased
      significantly at 15 degrees and 35 degrees of trunk flexion. The ratio of
      extension torque over RMS-EMG of the trunk extensor muscles, called the
      neuromuscular efficiency ratio (NMER), also increased in the more flexed posture.
      However, NMER has to be interpreted with caution because it is affected both by
      posture and exertion levels. The effects of posture on the torque generation
      capability of the trunk question the validity of the current lifting
      recommendations.

PMID- 8303453
TI  - Isokinetic trunk strength and lifting strength measures. Differences and
      similarities between low-back-injured and noninjured workers.
AB  - Fifty-eight back pain patients and 21 entry-level Postal Service workers without
      low-back pain were evaluated using a variety of lumbar function measures.
      Isolated trunk strength and full lifting strength were gauged with isokinetic and
      isometric methods. Lumbar range-of-motion was computed using toe-touch and
      goniometers. Conventional clinical techniques such as toe touch and straight leg
      raise were effective in distinguishing back-injured from normal subjects.
      Isometric and isokinetic peak force and torque tests failed to show significant
      differences between low-back pain and job applicant groups. When compared with
      published norms, our job applicant group was significantly deconditioned. Our
      data suggest that asymptomatic, deconditioned subjects could be mistaken for back
      impaired patients or symptom magnifiers.

PMID- 8303454
TI  - Sacral insufficiency fractures presenting as acute low-back pain. Biomechanical
      aspects.
AB  - Sacral insufficiency fractures are an often unsuspected cause of low-back pain in
      elderly women with osteopenia who have sustained unknown or only minimal trauma.
      The authors describe 10 cases of spontaneous sacral insufficiency fractures,
      confirmed by computed tomography, characterized by the onset of acute low-back
      pain. Differential clinical and radiographic diagnosis of these fractures is
      often difficult. Recognition of the characteristic scintigraphic patterns in
      sacral fractures, which are frequent in osteopenic patients, could avoid mistaken
      diagnoses and unnecessary tests or treatment. One of the striking feature of
      these sacral fractures is their invariable location. The fractures extend
      vertically in the sacral alae, parallel to the sacroiliac joints. They are
      located just lateral to the margins of the lumbar spine. This distribution
      suggests that such fractures could be partially caused by weight-bearing
      transmitted through the spine.

PMID- 8303455
TI  - Insufficiency fractures of the sacrum. Twenty cases and review of the literature.
AB  - Over the past 10 years, 231 insufficiency fractures of the sacrum have been
      reported in the literature. These fractures, which are due to osteopenia, form a
      distinct subgroup of pathologic fractures. In 1.8% (n = 20) of the older-than-55
      years female patients (total = 1,015) admitted to the authors' Rheumatology
      department between 1989 and 1991, a fracture of the sacrum was diagnosed. In all
      cases the diagnosis was confirmed with computed tomography. Frequency, age, sex,
      diagnosis, underlying diseases, and associated fractures of the 20 cases of
      insufficiency fractures of the sacrum are described and compared with those
      previously reported. Insufficiency sacral fracture as a cause of low-back pain in
      women older than 55 years of age is concluded to be a clinical entity.

PMID- 8303456
TI  - Bone mineral density of the radius in patients with ossification of the cervical
      posterior longitudinal ligament. A longitudinal study.
AB  - Radial bone mineral density (BMD) in the distal one sixth and distal one third of
      the left radius was measured by single-photon absorptiometry (SPA) in patients
      with ossification of the cervical posterior longitudinal ligament (OPLL). Twenty
      three OPLL patients (15 men and 8 women) with mean initial age of 60.1 years were
      studied longitudinally for mean follow-up period of 3.9 years. Based on
      roentgenologic findings, the patients were divided into two groups, those with
      advancing OPLL and those with non-advancing OPLL. The final value of distal 1/6th
      BMD in the advancing group was significantly lower than its initial value, but no
      change of the value of the distal 1/3rd BMD was observed in either group. The
      final value of distal 1/6th BMD/distal 1/3rd BMD ratio in the advancing group was
      significantly decreased compared with its initial value. These results suggest
      that, in the advancing OPLL group, trabecular bone mass decreased while cortical
      bone mass remained unchanged.

PMID- 8303457
TI  - Transpedicular decancellation closed wedge vertebral osteotomy for treatment of
      fixed flexion deformity of spine in ankylosing spondylitis.
AB  - Limitation of movement of the back, pelvis, chest wall, and other joints are the
      consequences of ankylosing spondylitis. The most serious problem is severe
      kyphosis leading to disturbance of the activities of daily living and failure of
      the respiratory system. Transpedicular decancellation closing wedge vertebral
      osteotomy, using the posterior approach followed by segmental spinal
      instrumentation, is a safe and easy technique for correction of the deformity.
      The authors report the results of this technique in six patients, five men and
      one woman, who had undergone the operation. The average age of the patients was
      29.8 years (range 21-38). Three patients had thoracolumbar kyphosis averaging 104
      degrees (range, 80-120), while the others had lumbar kyphosis averaging 46.7
      degrees (range, 35-60). The angles of correction in all cases average 33 degrees.
      Only one case in this report had dura tear due to adhesion between the dura and
      the ossified ligamentum flavum, which required exploration and repairing with
      myofascial graft. No case had any neurologic complication. At an average of 24
      months' follow-up, all cases had improvement of their general appearance,
      posture, respiratory and gastrointestinal functions, and had good bony union.

PMID- 8303458
TI  - Herpes zoster radiculopathy.
AB  - Herpes zoster-related radiculopathy usually can be easily diagnosed in the
      presence of cutaneous lesions. Before development of the skin rash, the diagnosis
      may be in doubt, particularly if motor symptoms and signs are a major clinical
      feature. We report a patient with herpes zoster-related radiculopathy whose
      clinical features mimicked other spinal disorders.

PMID- 8303460
TI  - Gas-containing "ganglion" cyst of lumbar posterior longitudinal ligament at L3.
      Case report.
AB  - A case of "ganglion" cyst was found to originate from the L3 lumbar posterior
      longitudinal ligament at the pedicular level. The patient had moderate lumbar
      degenerative scoliosis. The cyst had no connection with the intervertebral disc,
      dural sac, facet joint or nerve root. Instead of mucous or myxoid material, it
      contained gas. Pathology showed a thick collagenous fibrous wall with no
      particular linings. No synovial component could be found by immunohistochemical
      stains. Pathologic findings including hemosiderin deposition, chronic
      inflammatory cell infiltration, and calcified spots supported a chronic process
      of cystic degeneration of the ligament.

PMID- 8303459
TI  - Nonrheumatoid cranial settling.
AB  - Cranial settling is a condition in which erosive changes of the atlantal lateral
      masses result in downward telescoping of the atlas onto the axis body, anterior
      displacement of the atlantal posterior arch, and subsequent ventral and dorsal
      cervicomedullary compression. Cranial settling is described in conjunction with
      rheumatoid basilar invagination and atlanto-axial instability, possibly
      representing the most life-threatening abnormality associated with rheumatoid
      arthritis. The authors describe a case of symptomatic cranial settling in a
      nonrheumatoid patient with chronic, severe, spasmodic torticollis resulting in
      erosive changes in the occipito-atlanto-axial complex.

PMID- 8303461
TI  - Gas-containing lumbar disc herniation. A case report and review of the
      literature.
AB  - The finding of gas into the intervertebral disc space ("vacuum phenomenon") is
      relatively common, whereas gas-containing cervical or lumbar disc herniations are
      rarely observed. A case of a patient with bilateral leg pain, provoked by a
      computed tomography scan and surgically documented L4-L5 gas-containing disc
      herniation is reported and the cases previously described in detail are reviewed,
      to define the pathophysiologic and diagnostic aspects of this rare phenomenon
      associated with a herniated disc fragment.

PMID- 8303462
TI  - Lumbar facet stress fracture in a ballet dancer.
AB  - A frequent cause of back pain in athletes and dancers is stress injury to the
      posterior vertebral elements. Stress fractures affect the pars interarticularis
      and, rarely, other vertebral regions. The authors present their experience with
      the diagnosis and treatment of a fourth lumbar inferior articular facet stress
      fracture in a ballerina in this brief report and discuss the literature
      concerning posterior element stress fractures.

PMID- 8303463
TI  - Bilateral facet dislocation at the lumbosacral joint. A report of a case and
      review of literature.
AB  - Traumatic facet dislocation of the lumbosacral joint is uncommon. This report of
      a bilateral L5-S1 facet dislocation is compared with prior reported unilateral
      and bilateral cases with respect to mechanism of injury, neurologic injury,
      surgical reduction and fixation, and clinical outcome. Attention to the disk
      injury is recognized as essential to prevent cauda equina or root compression
      after reduction and fixation of the dislocation.

PMID- 8303464
TI  - Progressive scoliosis associated with lateral gaze palsy.
AB  - Two cases with progressive scoliosis and lateral gaze palsy were reported. The
      preoculomotor centers, which are connected by the fasciculus longitudinalis
      medialis in the brain stem, are deemed to be the common focus for progressive
      scoliosis and associated visual dysfunction.

PMID- 8303465
TI  - Postoperative Clostridium difficile pseudomembranous colitis in idiopathic
      scoliosis. A brief clinical report.
AB  - The authors report two healthy young patients with progressive idiopathic
      scoliosis, both without allergies or histories of gastrointestinal disorders, who
      received perioperative preventive cephalosporin antibiotics, and developed
      explosive diarrhea postoperatively, confirmed as Clostridium difficile
      pseudomembranous colitis by stool toxin assay. Both patients had initially
      recovered uneventfully after posterior fusion and Cotrel-Dubousset
      instrumentation. Their youth, health, diagnosis, and lack of nosocomial factors
      made colitis unexpected. The two cases were sporadic, occurring 2 years apart
      over a 12-year observation period. Symptoms and signs of colitis for the two
      patients were markedly varied as to time of onset, order of appearance, and
      severity. Unexplained fever before onset of diarrhea led to renewed cephalosporin
      administration, potentially exacerbating the colitis. Initial symptoms and signs
      were nonspecific; appropriate treatment had to begin before diagnosis could be
      confirmed by stool toxin asay, which requires 2 days.

PMID- 8303466
TI  - Atypical mycobacterial vertebral osteomyelitis in a steroid-dependent adolescent.
      A case report.
AB  - Atypical mycobacterial infections are uncommon, particularly in the spine. The
      authors present the case of a patient with vertebral osteomyelitis secondary to
      Mycobacterium chelonae subspecies abscessus that was successfully treated with
      surgical debridement and stabilization, followed by chemotherapy.

PMID- 8303467
TI  - Multiple spinal intradural schwannomas in the absence of von Recklinghausen's
      disease.
AB  - A case of multiple spinal schwannomas is reported without any evidence of other
      manifestations of neurofibromatosis. Although cases of multiple schwannomas have
      been described in the setting of "Schwannomatosis," this case is unique in that
      all tumors were within the spinal canal. The presence of a schwannoma should
      prompt a complete investigation for other tumors of the nervous system preferably
      with magnetic resonance imaging.

PMID- 8303468
TI  - [Screening mammography in British Columbia].

PMID- 8303469
TI  - [Adjuvant therapy of breast cancer: present status and the significance of new
      prognostic factors].

PMID- 8303470
TI  - [Classical prognostic factors in breast cancer].

PMID- 8303471
TI  - [Magnetic resonance imaging control studies following semitendinous cruciate
      ligament plasty].

PMID- 8303472
TI  - [The importance of magnetic resonance tomography in the detection of a thymus
      cancer. A case report].

PMID- 8303473
TI  - [Radical cystectomy in the therapy of bladder tumors].
AB  - Between January 1970 and December 1992, 100 patients (95 males and 5 females)
      underwent radical cystectomy for bladder cancer. Their mean age was 54.9 years
      (range, 34-74 years). Indications for radical surgery were multiple superficial
      tumors (pTa, pT1) in 24 patients and muscle invasive bladder cancer (pT2, pT3b)
      in 76 patients. Patients with invasive bladder cancer had received elective pre
      operative radiotherapy (40 Gy in 20 pts, 20 Gy in 18 pts). Seven patients had
      undergone salvage cystectomy after full-dose irradiation (60 Gy); 20 pts received
      pre-operative (neo-adjuvant) chemotherapy (M-VAC or CMV combination) and 11 pts
      had had no therapy before cystectomy. In 5 pts urinary diversion was performed in
      advance; in 95 pts cystectomy and urinary diversion were done at the same time.
      The following methods of urinary diversion were used: ureteroileostomy (Wallace's
      modification) in 80 pts, Mainz pouch I (ileal conduit with intermittent
      catheterization) in 6 pts, Mainz pouch with ileourethral anastomosis in 3 pts,
      ureterosigmoidostomy in 5 pts and Mainz pouch II (continent rectosigmoidal
      reservoir) in 6 pts. Post-cystectomy mortality was 8.0%. Long-term survival
      (Kaplan-Meier) following cystectomy was 15-20% of pts with invasive bladder
      cancer and 30-40% of pts with superficial bladder cancer.

PMID- 8303474
TI  - [Conn's syndrome in tumors of the adrenal cortex].
AB  - During the period from Jan. 1 1989 to June 30 1992 at the Urological Clinic in
      Hradec Kralove three women with cortical adenomas were treated, the tumour being
      the cause of primary hyperaldosteronism. The age of the patients was 25-40 years,
      in one woman the tumour was on the right side, in two on the left side. All
      patients complained of marked muscular weakness, fatigue, one woman developed
      cramps of the hands when working and another patient was repeatedly hospitalized
      at the neurological department on account of attacks of weakness. In one patient
      the interval from the onset of complaints to assessment of the diagnosis was 23
      years. All patients had complete examinations at specialized departments before
      operation, in all the diagnosis was established by biochemical examinations and
      CT. In all instances minor tumours--diameter 2-3 cm--were involved which were
      easily removed by surgery. The postoperative course in all patients was without
      complications.

PMID- 8303475
TI  - [Extra-adrenal pheochromocytoma].
AB  - In the course of 35 years at the Urological Clinic in Hradec Hralove 44
      pheochromocytomas were operated incl. 16 extraadrenal ones (36%). Eight men and 7
      women were operated. In five men and seven women a primary extraadrenal tumour
      was involved. In three men and the woman a relapse of an extraadrenal
      pheochromocytoma was operated. The mean age of the whole group of 12 patients
      operated on account of a relapse of a paraganglioma was 44 years. The time
      interval after the primary tumour was 3-16 years. Surgically six paragangliomas
      on the right side and 10 on the left side were operated. The paragangliomas on
      the right side were at the following sites: three behind the inferior vena cava,
      one tumour was a multiple one and two tumours were in front of the inferior vena
      cava. On the left side were two tumours above the bifurcation of the aorta, five
      were paraaortal and one tumour was on the aorta at the insertion of two renal
      arteries. Three tumours were in the hilus of the left kidney.

PMID- 8303476
TI  - [Tumor thrombosis of the inferior vena cava--personal experience with surgical
      therapy].
AB  - Patients treated at the Urological Clinic in Hradec Kralove on account of
      carcinoma of the kidney are systematically followed up since 1962. In the
      submitted paper the authors evaluate patients treated during 1985-1991. During
      the mentioned period at the Urological Clinic in Hradec Kralove 365 patients with
      carcinoma of the kidney were treated. In 55 (15%) invasion into the renal or
      inferior vena cava was proved (in 43 men and 12 women). In 38 patients the tumour
      with a thrombus of the inferior vena cava was on the right side, in 17 a tumour
      of the left kidney was removed. The right to left ratio is 2.2:1. Surgery of
      tumourous thrombosis depends on the level of the upper margin of the tumourous
      thrombus. A tumourous thrombus in the subhepatic part of the inferior vena cava
      can be treated either by massaging into the renal vein after obliteration of the
      artery or by parietal resection of the inferior vena cava. In 18 patients the
      authors were able to remove the thrombus by massaging into the renal vein. In 32
      patients the inferior vena cava was resected. In five the tumourous invasion was
      not resolved, either because of extensive secondaries (in the liver and lungs) or
      because of direct tumourous infiltration of the wall of the inferior vena
      cava.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8303477
TI  - [Prevention of hematoma and edema after scrotal surgery].
AB  - Postoperative hematoma and edema are the most frequent complications of scrotal
      surgery. The authors refer their own experience with a simple, reliable method
      for prevention of postoperative hematoma and edema described by Oesterling.

PMID- 8303478
TI  - [Flexible cystoscopy in clinical and ambulatory practice].
AB  - The author describes his own experience with more than 500 examinations with
      flexible cystoscope. General technical parameters, differences in manipulation
      and various problems in evaluation of findings are mentioned. In spite of much
      higher price as compared with rigid instruments, the use of flexible cystoscopes
      has been advocated because of their medical advantages and patient's comfort.

PMID- 8303479
TI  - [Congenital epispadias with urinary incontinence: long-term results of
      reconstructive therapy].
AB  - The author investigated the long-term results after reconstruction operations in
      epispadias with total urinary incontinence in 16 pediatric patients-4 girls and
      12 boys. The patients were operated in 1961-1981 at the Department of pediatric
      surgery of the University Hospital in Hradec Kralove. The operations were made
      most frequently between the age of 3 and 4 years. Straightening of the penis was
      achieved by exstirpation of the dorsal chorda and by V-Y plasty. To lengthen the
      penis it proved useful to separate the greater portion of the crura from the bony
      rami. To achieve functional continence plastic operations were made of the
      posterior urethra and of the bladder neck in patients of both sexes. The Young
      Dees procedure proved best. The overall continence rate was achieved in 70% of
      operated boys and in 60% of girls. The functional failure of reconstruction was
      treated by secondary diversion in 2 cases, in one by ureterosigmoideostomy and in
      one by ileal conduit. The associated VUR reflux was corrected by Politano
      Leadbetter's UCN or by the Cohen procedure. From the social aspect the patients
      are well adapted, they completed their training for a job. Of 12 patients where
      an inquiry for further information was made, with the exception of one patient,
      all are active in their sexual life. Seven patients are married, five men
      fathered 7 children and two female patients were delivered of three healthy
      children.

PMID- 8303480
TI  - [Use of the Convatec Wound Manager and Stomahesive flanges in local treatment of
      external gastrointestinal fistulas].
AB  - The authors used in 1989-1992 for local treatment of postoperative external
      gastrointestinal fistulas the Wound Manager of Convatec Co. This aid ensures
      perfect protection of the skin, a good access to the fistula and dehiscent wound
      and accurate removal and measuring of the secretion. The authors used as an
      alternative method Stomahesive Convatec flanges with permanent suction. In this
      way during the above mentioned period 16 patients were treated at the Surgical
      Clinic of the Institute for Postgraduate Medical Training, Faculty Hospital
      Bulovka in Prague. Thirteen patients were treated by conservative methods only,
      but also in the remaining three prolonged conservative treatment made the
      operation possible. The total lethality was 25%. The authors recommend these aids
      as an integral part of comprehensive treatment of postoperative enterocutaneous
      fistulas.

PMID- 8303481
TI  - [Ischemic colitis].
AB  - Based on experience with 12 patients with ischaemic colitis observed in 1968-1992
      the following conclusions can be drawn: ischaemic colitis is not as rare as
      assumed and its rising incidence must be foreseen. The clinical picture is not
      typical, but when suitable diagnostic methods are used, it can be diagnosed in a
      large number of cases. In non-complicated cases the prospects of conservative
      treatment are good. Surgery is associated, with regard to the age of the majority
      of patients, with a considerable risk. Therefore decisions on surgery should be
      made by the surgeon in cooperation with the gastroenterologist.

PMID- 8303482
TI  - [Perianal pyoderma].
AB  - Perianal pyoderma (hidradenitis suppurativa-acne conglobata) is a chronic disease
      which in its progressive form cannot be treated by conservative methods.
      Extensive suppurative foci must be radically excised incl. all systems of
      fistulas right down to the fascia and the defects which develop are allowed to
      heal per secundam or after several weeks they can at a different period of time
      be covered by a skin transplant. The authors present their 30-year experience
      with surgical treatment of 39 patients. Treatment was in all instances successful
      after radical surgical excision. All these patients have fully recovered as
      regards work capacity as well as social aspects.

PMID- 8303483
TI  - [Laparostomy as a part of intensive surgical care].
AB  - The presented paper is based on an analysis of 24 cases where as part of
      comprehensive surgical care the laparostomic procedure was used. In nine patients
      advanced diffuse peritonitis was involved, nine times the method was applied in
      patients with haemorrhagic necrotizing pancreatitis, four times in intestinal
      ischaemia and twice as a temporary closure of an extensive defect of the
      abdominal wall. In all instances a zipper of Ethicon Co. was used. Eight patients
      died i.e. lethality was 33%. The main contribution of the method is according to
      the authors the possibility of easy repetition of the surgical intervention in
      the abdominal cavity with elimination of septic foci and effective decompression
      of the abdominal cavity which has a positive impact on ventilation.

PMID- 8303484
TI  - [Professor Karel Neuwirt, (1893-1970) a founder of Czech and Slovak urology].

PMID- 8303485
TI  - Women workers: international issues.
AB  - Disparities in women's working conditions, health care, and general treatment
      between developed and developing countries will continue to grow unless the
      status of women in developing countries receives priority attention. Government
      attempts in Third-World countries to improve the status of women are hampered by
      socioeconomic factors, explosive population growth, and a deepening world
      economic crisis. Health care in the developing world is almost nonexistent. In
      developing countries, health care facilities are not within walking distance of
      85% of the population. Women not only are subject to many of the same health
      problems as men, but also face discrimination on the basis of sex, lower
      socioeconomic status and the physical demands of childbearing and family care.
      Improvement in women's health and status is basic to the development of society.
      Developing countries cannot achieve their economic goals unless they recognize
      that the health of all citizens is of primary importance and that women must be
      permitted to be part of the development process equally with men.

PMID- 8303486
TI  - Sex, gender, biology, and work.
AB  - Women are entering the paid workforce in increasing numbers and breaking into
      traditionally male occupations, causing a demographic shift in the work force.
      Moreover, because women have attained greater reproductive freedom with birth
      control, they are no longer tied by biologic necessity to reproduction and child
      care. As a result, some of the underlying assumptions about women and work have
      been challenged. This chapter explores the biologic differences between men and
      women and how these differences may affect job capacity and compatibility. It
      also reviews the controversy over gender roles and resulting occupational
      segregation and pay disparity.

PMID- 8303487
TI  - Women, occupation, and risk of cardiovascular morbidity and mortality.
AB  - Despite the many investigations of male workers, little is known about
      cardiovascular risk attributable to occupational class or occupational exposures
      among women. Results from a previous investigation suggest that the relationship
      between these factors may be different in women, for whom lack of workplace
      social support may be important in cardiovascular morbidity. The finding that
      women in blue-collar occupations had over three times the rate of coronary heart
      disease compared with their white-collar equivalents is intriguing. Modest and
      inconclusive data about the relationship between occupational stress and health
      status in women suggest that class and level of control may be of importance in
      women's experience of occupational stress.

PMID- 8303488
TI  - Women and ergonomics.
AB  - The significant rise in the number of women and minorities in the work force and
      their economic importance necessitate a different approach to human factors and
      ergonomics. This approach requires research to develop anthropometric and
      biomechanic data describing the reality of the current and projected work force
      and application of the data to all aspects of the worksite, from tool and
      furniture design to sophisticated information-processing equipment such as voice
      activated computers. Failure to do so will perpetuate the rising rate of injuries
      due to ergonomic hazards.

PMID- 8303489
TI  - Occupational reproductive health risks.
AB  - The potentially harmful effects on women of certain workplace exposures are
      widely appreciated, and steps to control these have included legislative efforts
      such as right-to-know laws of well as corporate policies mandating selective
      restriction of fertile women, which are illegal under federal civil rights laws.
      This chapter reviews the various occupational health risks reproductive women
      face in the workplace but also considers the effects of other genetic, medical,
      social, infectious, and environmental factors which may be of even greater
      concern than most occupational factors.

PMID- 8303490
TI  - Reproductive hazards: a model protection policy for the chemical industry.
AB  - This chapter is based on research sponsored by the chemical industry to develop
      practical guidelines for protecting employees exposed to reproductive hazards in
      worksites for which reduction in exposure levels to safe limits is not possible.
      Because relatively little information is available to permit the establishment of
      acceptable exposures, a related section of the research was done by toxicologists
      to address the issue of identifying reproductively hazardous sites. The policy
      was designed to be implemented in the context of high uncertainty as to what
      risks actually exist.

PMID- 8303491
TI  - Depression, women, and the workplace.
AB  - Depression is a highly prevalent disorder that causes much personal distress and
      difficulties in functioning at home and in the workplace. In the workplace, as
      elsewhere, depression can manifest as a variation in normal mood, as a symptom,
      as a disorder, or as a disease. Occupational health professionals are more
      concerned with clinical depression, a term used to signify any type of depression
      that causes significant personal distress and/or problems in functioning.
      Clinical depression is manifest in the workplace and adversely affects the
      employee's work satisfaction and performance. For most types of depression, women
      are at a higher risk than men. A number of events and variables related to women
      and depression were reviewed. Although the effects of some of these events, such
      as menopause, can be manifest in the workplace, they are not associated with an
      increased incidence of clinical depression. Other events, such as victimization
      (e.g., childhood sexual abuse or battering by an intimate partner), are
      associated with higher risks of depression in women. Women derive substantial
      satisfaction from interpersonal relationships but also are at greater risk for
      depression when strains and conflicts in these relationships occur. In the
      workplace women who have no difficulty in arranging for child care and whose
      spouses share in the care of children show lower rates of depression. When
      marriages are unhappy, women are three times as likely as men to be depressed.
      These findings speak to the importance of relationships to women. In the
      workplace, when women are depressed, problems with relationships are likely to be
      involved. Clinically depressed women are not difficult to identify in work
      settings. Dejected mood and loss of interest in usual activities are noticeable,
      along with numerous other symptoms that accompany depression. The effective
      treatment of depression depends on careful diagnosis and assessment. Both drug
      therapy and the more structured psychotherapies, such as cognitive-behavioral and
      interpersonal therapy, have demonstrated effectiveness in treating depression.
      For mild depression, pharmacotherapy is likely to be the treatment of choice. In
      cases in which the depressive symptomatology is moderate to severe, a combination
      of drug therapy and psychotherapy is likely to be the most effective treatment
      and to provide the best prophylaxis. Drug therapy seems particularly effective in
      promoting rapid reduction of vegetative and physical symptoms. Psychotherapy
      enhances coping skills at home and at work and also focuses on problem-solving,
      relationship difficulties, and dealing with stressors. In the area of prevention,
      occupational health practitioners currently can have the greatest impact in
      secondary prevention.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8303492
TI  - Social and psychological aspects of illness--past and present.
AB  - As industrialization and automation spread in the workplace in the 19th century
      and economic needs shifted, one major cultural response was to redefine the
      nature of women as fragile physically, intellectually inferior, and too
      emotionally unstable to stand the rigors of the workplace. These views persist
      today, as women are back in the workforce in numbers higher than ever. The
      elements in society, home, and workplace that contribute to absenteeism, poor or
      inconsistent performance, and depression among women are reviewed. This chapter
      reviews the historical events in the saga of women in the workplace and analyzes
      the contemporary status of those who are striving toward better work environments
      and greater occupational health for women workers.

PMID- 8303493
TI  - Effects of sexual harassment on women and organizations.
AB  - This chapter focuses on the consequences of sexual harassment of women, including
      the effects on the victim's work and health and the organization for which she
      works as well as the woman's attempts to cope with harassment when confronted
      with it. The responses of victims are influenced by the amount of support and
      understanding they receive from significant others and employers. The extent of
      emotional, physical, and psychological damage depends on the responsiveness of
      other people and the organization for which the woman works.

PMID- 8303494
TI  - Combining work and home.
AB  - The health consequences for women of combining work outside the home with
      domestic responsibilities are reviewed. The chapter evaluates role stress as a
      function of multiple roles and concludes that such juggling promotes women's
      health by offering increased variety of functions performed as well as increased
      emotional buffering. The chapter also concludes that women's working outside the
      home has a positive effect likewise on children and spouses.

PMID- 8303495
TI  - Women's and men's responses to sex-segregated work.
AB  - Research on the consequences of sex segregation at work has focused mainly on
      economic consequences rather than affective outcomes. This chapter discusses how
      the sex composition of women's and men's work settings affects their
      psychological well-being and job satisfaction. Research discussed here shows that
      sex composition can affect satisfaction directly rather than simply serving as a
      proxy for rewards and working conditions.

PMID- 8303496
TI  - Gender, disability, and employment.
AB  - This chapter traces the employment picture for women with disabilities over the
      last two decades. It shows that supply-based explanations, such as medical need
      or willingness to work, do not explain the proportion of persons with
      disabilities in the workforce as well as general labor-market trends do. The
      growth of the service industry has provided more opportunities for women with
      disabilities to join the labor force over the last two decades, but often in
      roles of part-time work, less job security, lower pay, and little or no benefits.

PMID- 8303497
TI  - Working women: economic and social considerations.
AB  - The social, political, and economic forces that have drawn women into the labor
      force are complex and interrelated. This chapter presents four major concerns of
      working women: gender wage differentials, working hours and flexible schedules,
      nonwage compensation, and working conditions. Women are a relatively recent
      phenomenon in the work-for-wages market, and their specific economic concerns are
      not well understood by society. As their numbers increase in the workplace, these
      concerns will assume greater importance.

PMID- 8303498
TI  - Women and agricultural work.
AB  - Women farm workers are exposed to a multitude of biologic, chemical, physical,
      and mechanical hazards. High rates of machinery-related accidents and respiratory
      occupational illnesses are seen among agricultural workers. Many occupational
      diseases in women go undiagnosed if the "farmer's wife" is not asked what she
      does on the farm or if the physician is unfamiliar with occupational disease.

PMID- 8303499
TI  - Current operating statistics: list of tables.

PMID- 8303500
TI  - Earnings of couples: a cohort analysis.
AB  - This article looks at Social Security covered earnings of wives relative to their
      own husbands, using interview responses from the 1990 Survey of Income and
      Program Participation linked to Social Security Administration records of covered
      earnings. It examines earnings at ages 22-31, 22-41, and 22-51 for birth cohorts
      of wives born in the 1930's, 1940's and 1950's. More recent cohorts of wives had
      more years of earnings and higher levels of indexed earnings. As expected,
      differences in earnings of wives relative to their husbands declined among more
      recent cohorts. Nevertheless, if these earnings patterns continue through
      retirement age, the majority of wives born in the 1930's and 1940's and two
      fifths of those born in the 1950's can expect to receive spouse benefits, and, if
      widowed, most can expect to receive widow benefits based on their husband's
      covered earnings. The article explores which characteristics are significantly
      associated with wives having low earnings relative to their husbands.

PMID- 8303501
TI  - Pension vesting and preretirement lump sums among full-time private sector
      employees.
AB  - Vesting among full-time private sector employees has increased dramatically over
      the past two decades. With further increases expected, it seems likely that
      almost all workers covered by a pension plan will eventually receive some kind of
      benefit. Coverage, however, remains a problem. According to the most recently
      available data, only 46 percent of full-time private employees in 1988 were
      covered by a pension plan on their current jobs, 35 percent were vested, and an
      additional 4 percent were vested from a previous job. Vesting rates would have
      been higher if some workers had not cashed out their retirement benefits when
      they left previous jobs, but the impact is slight; most lump-sum recipients were
      also vested or covered on their current jobs. Vesting is higher among older
      workers and among men, though the gender gap has narrowed appreciably over time.
      Based on trends in vesting and 1988 rates for all types of workers aged 50-59,
      the analysis suggests that pension receipt rates among the elderly will continue
      to increase over the next decade.

PMID- 8303502
TI  - Women's employment and the Social Security system.
AB  - The rapid rise in women's labor-force participation and the great increase in
      diversity of family and household structures raise serious questions about the
      equity and adequacy of a Social Security system developed primarily to meet the
      needs of traditional families with male wage earners and female homemakers. This
      article examines the changes in women's roles in the home and in the labor
      market, then goes on to consider possible reforms in the Social Security system
      that might help it to better meet the requirements of this profoundly altered
      society.

PMID- 8303503
TI  - Treatment of women in the U.S. Social Security system, 1970-88.
AB  - This article, a reprint of a paper presented in 1988 to the International Social
      Security Association, traces the debate from 1970 through 1988 over treatment of
      women in the Social Security system. It traces issues relating to working women,
      couples with two earners, homemakers, widows, and divorced women. It describes
      the debate that led to widespread support for the concept of earnings sharing. It
      then addresses the paradox that despite continued widespread support for earnings
      sharing, despite continuation of the factors underlying its proposal, by 1988 no
      comprehensive legislation related to the treatment of women under Social Security
      had been enacted nor was being generally contemplated. This is still true in
      1993. The article argues that apparently insoluble, inherent conflicts among the
      objectives underlying earnings sharing ultimately doomed its enactment. Cost
      considerations, the realization of unintended side effects, and issues relating
      to transition to a very different Social Security system also helped remove
      earnings sharing from the legislative agenda. The article also describes the role
      policy analysis played in the debate over this proposed reform.

PMID- 8303504
TI  - Workers' compensation: coverage, benefits, and costs, 1990-91.
AB  - Workers' compensation programs provide protection to workers and their families.
      The programs compensate for lost wages and medical expenses incurred as a result
      of work-related injuries or illnesses. Survivor benefits are also provided when
      the disabilities result in death. In 1991, about $16.8 billion in medical
      benefits and $25.3 billion in wage-loss compensation was paid in settlement of
      claims filed for disabled or deceased workers. These benefits were paid by
      private carriers, by State funds, or by self-insuring companies as determined by
      laws in each State. The employer's cost of providing workers' compensation
      coverage generally varies according to risk, industrial classification, and
      experience rating. Nationally, such costs were approximately 2.4 percent of
      payroll or about $590 for each of the 93.6 million protected employees. This
      article examines the recent changes in coverage, in benefit levels, and in
      employer costs and the factors influencing such changes. Over the past decade,
      workers' compensation benefits have increased by 157 percent and employer costs
      by 143 percent. In the same period, the number of covered employees has risen 22
      percent and the amount of covered wage and salary payroll, 77 percent.

PMID- 8303505
TI  - Sampling variance estimates for SSA program recipients from the 1990 Survey of
      Income and Program Participation.
AB  - Since 1987 the Social Security Administration (SSA) has published a special set
      of tabulations on SSA program recipients in the Annual Statistical Supplement to
      the Social Security Bulletin using data derived from the Census Bureau's Survey
      of Income and Program Participation (SIPP). Estimates of sampling errors
      pertaining to these tabulations were derived from the 1984 SIPP panel. This
      article provides updated sampling error estimates for the 1990 SIPP panel to be
      used in conjunction with the SIPP-based tabulations provided in the Annual
      Statistical Supplement for 1992 and 1993. The computational approach is
      essentially the same as that used in the earlier analysis. Sampling variances are
      estimated by half-sample replication using the pseudo stratum and half-sample
      codes available on SIPP public use data files. Generalized tables of standard
      errors are provided for all SSA program participants. An appendix provides
      detailed specifications about the calculations. In order that it be self
      contained, this article repeats much of the methodological exposition in the
      previous article that appeared in the October 1988 issue of the Social Security
      Bulletin.

PMID- 8303506
TI  - Statistical notes from the New Beneficiary Data System.
AB  - The New Beneficiary Data System (NBDS), developed by the Social Security
      Administration (SSA) over the past decade, is an increasingly important source of
      information on the changing circumstances of aged and disabled beneficiaries.
      Based initially on a survey of new beneficiaries conducted in 1982, the data set
      was subsequently enhanced with information from administrative records, and, in
      1991, through followup interviews with survivors from the original survey. All
      data, of course, meet rigorous standards for the protection of individuals'
      privacy and confidentiality. Beginning with this issue of the Social Security
      Bulletin, we will be presenting brief statistical reports from the New
      Beneficiary Data System, with special emphasis on the results of the New
      Beneficiary Followup survey; more extensive analyses will follow.

PMID- 8303507
TI  - Dental fear treatment outcomes for substance use disorder patients.
AB  - In order to examine the clinical treatment outcome for dental fears, we compared
      the records of 18 phobics who had co-morbid substance use disorder (SUD) with
      those of 27 subjects who were phobic without concomitant SUD. Outcomes were
      determined by calculation of changes in the Dental Fear Survey (DFS) score.
      Subjects were classified by the Structured Clinical Interview for DSM-III-R. All
      subjects received exposure-based behavioral therapy with or without
      pharmacological adjuncts. All 27 subjects in the non-SUD group and 15 of 18
      (83.3%) of subjects in the SUD group improved. Non-SUD subjects improved more
      than SUD's on the avoidance and specific fear, but not on the physiological
      upset, dimensions of the DFS.

PMID- 8303508
TI  - Computer-based education for evaluation of oral lesions.
AB  - This paper describes the development of a computer-based educational module for
      dental students, dental hygiene students, and dental practitioners and instructs
      the user in screening activities for oral lesions associated with cancer or the
      HIV virus.

PMID- 8303509
TI  - The utilization of a multi-layer prosthesis to treat recurrent antral carcinoma:
      a case report and review of the literature.
AB  - This paper reviews the use of an intracavitary mold in the radiotherapeutic
      management of recurrent sub-orbital carcinoma of the maxillary sinus. An overview
      of the clinical features of antral carcinomas and the concept of brachytherapy in
      the management of these lesions is presented. Brachytherapy is usually reserved
      for relatively accessible lesions. Post-surgical and radiation-induced trismus
      can be a complicating factor, as in the case presented, where the inter-incisal
      distance was less than three millimeters. To circumvent the problem, a multi
      layer antral plug was utilized as a carrier for the radioactive sources, and its
      construction is described.

PMID- 8303510
TI  - Management of orofacial manifestations of Parkinson's disease with splint
      therapy: a case report.
AB  - Patients with Parkinson's Disease display a number of orofacial manifestations.
      These manifestations are secondary to motor and sensory deficits, resulting in
      bradykinesia, muscle rigidity and tremor, and difficulties with speech,
      swallowing, proprioception, tactile sensitivity, and hard- and soft-tissue
      trauma. This case describes the use of a bruxism splint which benefited a PD
      patient by diminishing the occurrence of orofacial pain secondary to muscle
      tremor and rigidity while reducing the cumulative damage to the oral structures
      common with the disease. The impact of therapy on sleep, speech, and swallowing
      difficulties is also discussed.

PMID- 8303511
TI  - Late effects of head and neck radiation therapy and patient/dentist compliance
      with recommended dental care.
AB  - Head and neck radiation therapy patients have permanent damage to their salivary
      glands, tissue, and bone. This damage may result in late effects such as:
      xerostomia, rampant dental caries, demineralization, trismus, and
      osteoradionecrosis. Therefore, a pretherapy dental evaluation and treatment and
      compliance with a long-term oral care regimen are necessary. This retrospective
      study was designed to assess the late effects of radiation therapy and compliance
      with long-term care recommendations of patients seen in the Oncology Dental
      Support Clinic at the University of Missouri-Kansas City School of Dentistry
      during 1981 to 1989. Telephone interviews of patients and their dentists were
      conducted, and a written questionnaire to the dentists provided further data.
      Late effects were consistent with those reported in the literature. A compliance
      rate of approximately 50% was reported. Several measures have been implemented in
      an attempt to increase compliance.

PMID- 8303512
TI  - Nasopharyngeal carcinoma: a 15-year retrospective study.
AB  - Malignancy in the nasopharynx, although uncommon, is potentially devastating
      because of the anatomy of the region and benign early symptoms, which result in
      infrequent early diagnosis. High-dose radiation therapy, with fields including
      the oral structures, is the treatment of choice and may result in significant
      oral complications. This paper reviews 39 cases of nasopharyngeal carcinoma
      diagnosed at the University of North Carolina Hospitals over a 15-year period.
      Patient demographics, histopathology, presenting signs and symptoms, stage at
      diagnosis, possible risk factors, treatment modalities, survival, side-effects of
      therapy, and dental intervention are reported.

PMID- 8303513
TI  - Use of medications with potential oral adverse drug reactions in community
      dwelling elderly.
AB  - Prevalence and indicators of medication use with potential oral health
      implications among 4,163 people from the Duke Established Populations for
      Epidemiologic Studies of the Elderly were studied. Medications were grouped into
      seven potential oral adverse drug reaction (POADR) categories. Eighty percent of
      participants were taking at least one medication from any of the seven
      categories. Drugs with the potential to cause xerostomia were taken by 56.1%,
      abnormal hemostasis by 51.7%, soft tissue reactions by 23.4%, taste changes by
      11.0%, alteration in host resistance by 8.7%, gingival overgrowth by 5.0%, and
      movement disorders by 2.4% of participants. Race-stratified analyses revealed
      that medication use with any POADR was significantly associated (p < 0.001) with
      being female for both races. Among nonblacks, being > or = 75 years old was
      associated with higher POADR use. Blacks who had a dental visit in the previous
      six months were more likely to take medications with POADR than those who did
      not. POADR medication use was not related to place of residence. Elderly often
      take medications with potential oral health impact.

PMID- 8303514
TI  - Evaluation of advanced general dentistry education.

PMID- 8303516
TI  - Small-diameter prosthetic H-graft portacaval shunt.

PMID- 8303515
TI  - Cytokines, sepsis, and the surgeon: a perspective.

PMID- 8303517
TI  - In situ vein bypass for peripheral vascular disease: laboratory and clinical
      observations.

PMID- 8303518
TI  - The role of renal revascularization in ischemic nephropathy.

PMID- 8303519
TI  - Clinical use of assisted circulation.

PMID- 8303520
TI  - Advances in fetal surgery.

PMID- 8303521
TI  - Advances in the surgical treatment of disorders of the shoulder.

PMID- 8303522
TI  - The use of greater omentum in reconstructive surgery.

PMID- 8303523
TI  - Recent advances in anorectal physiology.

PMID- 8303524
TI  - An approach to the treatment of encopresis.

PMID- 8303525
TI  - Surveillance in patients with stage I nonseminomatous testicular tumors.

PMID- 8303526
TI  - [Medically assisted procreation. Techniques and results].

PMID- 8303527
TI  - [The place of the laboratory in medically assisted procreation].

PMID- 8303528
TI  - [Medically assisted procreation. Medical viewpoint].

PMID- 8303529
TI  - [Medically assisted procreations: what about ethics].

PMID- 8303530
TI  - [Multiple pregnancies in medically assisted procreation. Information and informed
      consent].

PMID- 8303531
TI  - [Such a long course ...].

PMID- 8303532
TI  - [Fever and pregnancy].

PMID- 8303533
TI  - [Treatment of genital prolapse].

PMID- 8303534
TI  - [Urinary stress incontinence associated with a prolapse. Preoperative
      rehabilitation].

PMID- 8303536
TI  - [Clinical assessment in nursing].

PMID- 8303535
TI  - [Taking charge of patients who were operated for prolapse].

PMID- 8303537
TI  - [Birth control and abortion in Europe].

PMID- 8303538
TI  - [Development of a pedagogical project: nursing of children in pain].

PMID- 8303539
TI  - [Important reforms].

PMID- 8303540
TI  - [Child and adolescent nutrition].

PMID- 8303541
TI  - [Anatomical description of genital prolapse].

PMID- 8303542
TI  - [Fever convulsions].

PMID- 8303543
TI  - [Demand for voluntary interruption of pregnancy].

PMID- 8303544
TI  - [Symptoms and paraclinical investigations of prolapse].

PMID- 8303546
TI  - [Nursing service and the demand for care. Equipes soignantes].

PMID- 8303545
TI  - [Biological diagnosis of HIV infections in children].

PMID- 8303547
TI  - [Jean-Baptiste].

PMID- 8303548
TI  - [Ronald].

PMID- 8303549
TI  - [Julie].

PMID- 8303550
TI  - [AIDS and hygiene. Nursing care teams].

PMID- 8303551
TI  - [Psychological approach to AIDS].

PMID- 8303552
TI  - [The pediatric and rehabilitation center at Bullion, a place to stay for
      children].

PMID- 8303553
TI  - [Social service at the Pediatric and Rehabilitation Center].

PMID- 8303554
TI  - [History of 2 children under family placement].

PMID- 8303555
TI  - [Education and courses of study for children with HIV infection in long-term
      care].

PMID- 8303556
TI  - [Helping a dying infant to live].

PMID- 8303557
TI  - [Dietetics in acute infant diarrhea without severe dehydration].

PMID- 8303559
TI  - [Gloves].

PMID- 8303558
TI  - [Concentrate of potassium chloride].

PMID- 8303560
TI  - [Treatments of allergy].

PMID- 8303561
TI  - [The nurse's role in taking care of allergies].

PMID- 8303562
TI  - [The allergic child in school. Equipe du Service de promotion de la sante en
      faveur des eleves].

PMID- 8303563
TI  - [Speaking of allergy].

PMID- 8303564
TI  - [The role of the school nurse. Equipe de medecine scolaire].

PMID- 8303565
TI  - [Identifying asthma in the field. Health promotion team for students].

PMID- 8303566
TI  - [Asthma explained to the teachers. School medical team].

PMID- 8303567
TI  - [Dealing with pain in a neonatal rehabilitation center].

PMID- 8303568
TI  - [The allergens of children's environment. Their sensitizing role].

PMID- 8303569
TI  - [Nutrition for the pregnant woman].

PMID- 8303570
TI  - [A pathological cervico-vaginal smear].

PMID- 8303571
TI  - [Clinical forms of allergies and their diagnoses].

PMID- 8303572
TI  - Therapeutic effects of low radiation doses.
AB  - PURPOSE: This editorial explores the scientific basis of radiotherapy with doses
      of < 1 Gy for various non-malignant conditions, in particular dose-effect
      relationships, risk-benefit considerations and biological mechanisms. METHODS: A
      review of the literature, particularly clinical and experimental reports
      published more than 50 years ago was conducted to clarify the following problems.
      1. The dose-response relationships for the therapeutic effects on three groups of
      conditions: non-malignant skin disease, arthrosis and other painful degenerative
      joint disorders and anti-inflammatory radiotherapy; 2. risks after radiotherapy
      and after the best alternative treatments; 3. the biological mechanisms of the
      different therapeutic effects. RESULTS: Radiotherapy is very effective in all
      three groups of disease. Few dose-finding studies have been performed, all
      demonstrating that the optimal doses are considerable lower than the generally
      recommended doses, yet few of these studies meet the required standard. In
      different conditions, risk-benefit analysis of radiotherapy versus the best
      alternative treatment yields very different results: whereas radiotherapy for
      acute postpartum mastitis may not be justified any more, the risk-benefit ratio
      of radiotherapy of other conditions and particularly so in dermatology and some
      anti-inflammatory radiotherapy appears to be more favourable than the risk
      benefit ratio of the best alternative treatments. CONCLUSIONS: Radiotherapy can
      be very effective treatment for various non-malignant conditions such as eczema,
      psoriasis, periarthritis humeroscapularis, epicondylitis, knee arthrosis,
      hydradenitis, parotitis and panaritium and probably be associated with less acute
      and long-term side effects than similarly effective other treatments. Randomized
      clinical studies are required to find the optimal dosage which, at present, may
      be unnecessarily high. Since no adequate experimental studies have been performed
      nothing is known about the mechanisms of these therapeutic radiation effects.
      Good experimental models are now available which should be used to investigate
      the cellular and molecular mechanisms involved.

PMID- 8303573
TI  - Prognostic value of S-phase fraction in head and neck squamous cell carcinomas
      and nodal negative breast carcinomas.
AB  - PURPOSE: The prognostic value of proliferative activity (percentage of S-phase
      cells = SPF) was determined in head and neck and nodal negative breast carcinomas
      and correlated with treatment outcome and analysis of recurrence. METHODS AND
      MATERIAL: SPF of 171 primary squamous cell carcinomas of the head and neck and
      183 nodal negative breast carcinomas was determined by one-dimensional flow
      cytometry. RESULTS: For the whole population of head and neck carcinomas slowly
      proliferating tumors (SPF < median) had a better five-year survival rate (28%)
      than fast proliferating tumors (S-phase > median; 20% p < 0.05). Failure analysis
      revealed that the better survival of slowly proliferating tumors was due to the
      higher loco-regional control rate (62%) compared to fast proliferating tumors
      (43%; p < 0.05). Stepwise multivariate analysis revealed treatment modality (p =
      0.107), SPF (p = 0.026) and UICC stage (p = 0.044) as independent prognostic
      factors for loco-regional recurrences and SPF (p = 0.0143) for three-year overall
      survival. In nodal negative breast cancer slowly proliferating tumors (SPF <
      median) had a better NED survival (92%) compared to fast proliferating tumors
      (SPF > median; NED survival 63%). The analysis of recurrence revealed a higher
      rate of distant metastases (15.7%) and of loco-regional recurrences (21%) for
      fast proliferating tumors as compared to slowly proliferating tumors (distant
      metastases: 1.1%; loco-regional recurrences 4.5%). Stepwise multivariate analysis
      showed that SPF (p = 0.001) was the only independent prognostic factor for NED
      survival; grading (p = 0.022), age (p = 0.003) and SPF (p = 0.007) for freedom
      from distant metastases; SPF (p = 0.0039), grading (p = 0.0956) and method of
      surgical treatment (p = 0.0715) for loco-regional recurrences. CONCLUSIONS: SPF
      has a relevant prognostic power for squamous cell head and neck cancer and nodal
      negative breast cancer.

PMID- 8303574
TI  - [A critical consideration of the combined radiochemotherapy of head and neck
      tumors].
AB  - PURPOSE: Advanced tumors of the head and neck are often treated with combined
      radiochemotherapy. The chemotherapeutic agents used should be active in this
      tumor type and its adverse effects should not overlap with those of the radiation
      treatment. METHODS: Published studies were reviewed and discussed on the basis of
      these principles. RESULTS: Initially, single agents such as 5-fluorouracil (5-FU)
      and methotrexate were used in combination with radiotherapy. These combinations
      caused an improved local tumor control but also an increased mucosal reaction.
      For mitomycin C it has been shown in a randomized trial that local tumor control
      was improved without concomitant increased normal tissue toxicity. Also cisplatin
      and carboplatin were studied in combination with radiotherapy. Unfortunately,
      there are no results of randomized studies available but these agents do not seem
      to increase mucosal toxicity. The standard chemotherapy of squamous cell
      carcinomas of the head and neck is cisplatin and 5-FU. Many studies have been
      conducted with this chemotherapy in combination with radiotherapy. To this day it
      has not been shown that the results of an effective radiation treatment or an
      effective chemotherapy can be improved by these experiments. The explanation for
      that is that either the chemotherapy or the radiotherapy cannot be given at full
      dose because the regimen would become too toxic. CONCLUSION: 5-FU containing
      polychemotherapy regimens should not be combined with radiation any more because
      it is known that 5-FU increases the mucosal reaction. Agents that could be
      studied in the future either alone or in combination with cisplatin or
      carboplatin are etoposide and taxol.

PMID- 8303575
TI  - Linear quadratic model compared with TDF and TSD concepts for malignancy of
      cervix uteri treated with twice daily fractionated schedules.
AB  - PURPOSE: Various types of fractionation schemes have been tried in recent year
      with the objective of improving tumor control rate because conventional
      fractionation schedules do not always produce optimum results. To compare the
      radiobiological effectiveness and the gain in the therapeutic ratio due to
      various fractionation schemes, empirical formulae such as NSD, TDF, CRE and TSD
      were introduced and used despite of many short comings. Recent linear quadratic
      (LQ) model is claimed to be able to predict the radiobiological responses of
      tumor as well as normal tissues more accurately. In the present study various
      empirical models are compared. PATIENTS AND METHOD: We treated malignancy of
      cervix uteri by twice daily fractionation schedules of 1.2 Gy/fraction, 1.4
      Gy/fraction and 1.6 Gy/fraction with interfraction interval of four to six hours.
      The percentage tumor regression was estimated from weekly clinical observations
      and the TDFt, TSD and ERDt concepts were applied to the data and the predictions
      are compared. RESULTS: It was observed that TDFt and TSD concepts predicts
      equally well (within +/- 3%) the probable tumor regression as predicted by LQ
      concept. CONCLUSIONS: Till precise values of various parameters of LQ model are
      known, the TDF and TSD models can be used to predict probable tumor control rates
      within reasonable accuracy.

PMID- 8303576
TI  - A time-saving system for irradiations of experimental tumors.
AB  - PURPOSE: Experimental in vivo radiotherapy frequently aims at the imitation of
      clinically applied fractionation schedules. However, the reliability of the
      anesthetic procedure and limited access to the treatment machines in clinical
      departments are major factors complicating the practical realisation of the
      experiment. Therefore, a reliable and time saving system for irradiations of
      xenografted tumors has been developed, which allows repeated irradiations, even
      in relatively short intervals available for experimental irradiations. MATERIAL
      AND METHODS: The system presented here consists of an acrylic distributor for an
      anesthetic gas mixture employing enflurane (Ethrane) in the center of the set-up.
      Ten mice are positioned radially around the midpoint of the set-up so that they
      can be irradiated simultaneously. The xenotransplanted tumors growing on the
      right hind leg of mice are placed in a predefined position, which was found to be
      of advantage in order to position the tumors for fractionated treatments in
      identical setting. Tumor-bearing mice are irradiated with 15 MeV photons
      generated by a linear accelerator at a dose rate of 2.5 Gy/min. One of the
      significant feature of the setup is the ability to irradiate in acute hypoxia
      which is obtained by use of an integrated tourniquet. The dose modifying effects
      of different gases can be investigated by simply using them as carrier for the
      enflurane. RESULTS: With the use of the set-up several different experiments were
      performed so far. At most ten fractions were given, one fraction per day. Even
      after these repeated treatment the loss of animals due to narcosis was less than
      2%. The dose variation within the treatment field was found to be less than 4% as
      measured with TLD dosimetry. The remaining body of the mice is shielded
      effectively from the direct beam as the whole body dose of mice is 8% of the
      total tumor absorbed dose. The efficacy of the tourniquet technique for acute
      hypoxic irradiations was illustrated with the use of 99mTc-labelled albumin
      showing a complete stop of blood flow in the clamped leg. The steep dose-response
      curve obtained for single dose irradiation of a neurogenic sarcoma is based on
      the physical and experimental precision which can be reached with the technique
      suggested here. CONCLUSION: Due to the high dose rate and the possibility to
      irradiate ten animals simultaneously the set-up introduced here is greatly time
      saving. The versatile applicability makes the new set-up a valuable tool for
      tumor radiobiology.

PMID- 8303577
TI  - [An auxiliary system for optimizing the simulation and percutaneous irradiation
      of cranial-caudal contiguous head-neck-mediastinal fields].
AB  - PURPOSE: Percutaneous irradiation in the head and neck region via opposing
      lateral fields with caudally contiguous ventral and/or dorsal fields makes very
      high demands on simulation, instrument adjustment and documentation. At the outer
      boundaries of the irradiation volumes, there is always the danger of overdosage
      or underdosage with the familiar consequences. METHODS AND MATERIALS: Four
      targeting systems in one plane were inserted in a perspex frame each consisting
      of two concentric rings and two orthogonal crossbars. Under simulation
      conditions, the lateral radiation fields take up one half of the targeting
      systems and the ventro-dorsal fields occupy the remaining half. The corresponding
      targeting systems project exactly on or into each other with compensation of the
      beam divergence. RESULTS: A definitively exact irradiation via cranio-caudally
      contiguous fields with different incident beam direction is possible by using the
      four targeting systems in one plane. Compensation of divergence is aimed for by
      rotation of the table and gantry angle modification, errors of compensation can
      already be checked optically from 0.5 degree. Deviations of 5 mm in the simulated
      longitudinal arrangement of the contiguous fields can be imaged on the
      documentation film made with therapy activity. CONCLUSION: On the one hand, the
      auxiliary system presented allows both recognition of undesired field overlap and
      gaps in contiguous fields with different incident beam direction. On the other
      hand, it can be unequivocally documented whether the therapy is correct.
      Treatment errors can thus be minimized.

PMID- 8303579
TI  - [Protracted infusion versus bolus administration of 5-FU in adjuvant
      radiochemotherapy of rectal cancer].

PMID- 8303578
TI  - [Dosimetric studies using glass fibers].
AB  - PURPOSE: Ionizing radiation may cause discolouring of glasses by creation of
      colour centers. So radiation induced optical loss is a measure of absorbed dose.
      With a doped glass fiber a small volume optical dosimeter is developed for
      clinical purposes providing real time dosimetry with high spatial resolution.
      MATERIALS AND METHODS: Discolouring of glass by ionizing radiation is dose
      dependent and can be measured as light attenuation at a fixed wavelength. Light
      power of usual light emitting diodes (LED) is sufficient for this purpose. The
      readout light is conducted through a transmission fiber of arbitrary length.
      Concurrent measurements were performed at several wavelengths (660 to 850 nm)
      using a time multiplexing technique. We investigated the radiation induced light
      attenuation of a lead doped silica fiber with 60 Wt-% PbO2, diameter < 0.5 mm,
      and length < 0.1 m. The fiber was exposed to high energy photons of cesium-137,
      cobalt-60, 12-MV-photons, and 18-MV-photons generated by a linear accelerator,
      respectively. The influence of various temperatures, doses, and dose rates was
      tested. When sensor fiber is termed by a mirror reflected light can be detected
      with one transmission fiber and optical pathway is doubled. RESULTS: In a wide
      dose range (0 to 112 Gy) radiation induced loss represents absorbed dose in a
      linear manner without saturation effects. Optical loss is diminished by partial
      recovery of radiation damage depending on time and temperature. In order to
      compensate fading a phenomenological model was fitted to experimental data.
      Temperature dependence may be corrected by measurements with several readout
      wavelengths. Above 1 MeV there is merely a slight dependence on photon energy. At
      a size of the glass fiber reflection sensor of L = 2 cm doses of 0.04 Gy may be
      detected. The reproducibility at 1 Gy is about 4%. CONCLUSION: Lead doped silica
      fiber is suitable for radiation dosimetry in a dose range interesting for
      clinical practice. Fading may be compensated during irradiation using a
      phenomenological model. The size of a reflection sensor is comparable to
      thermoluminescence dosimeters. In contrast to TLD glass fiber provides real time
      dose measurements. By this means optical glass fiber dosimeter may be appropriate
      for in-vivo dosimetry in radiation therapy.

PMID- 8303580
TI  - [The negative effect of prolonging the total treatment time in cervix cancer].

PMID- 8303581
TI  - [The value of radiochemotherapy in marginally resectable non-small-cell lung
      carcinoma].

PMID- 8303582
TI  - Assessment of the risks associated with the breast-conserving treatment of ductal
      in situ carcinoma.

PMID- 8303583
TI  - [Combined radiochemotherapy of head and neck tumors].

PMID- 8303584
TI  - [On the choice of publications under the rubric "Comments on the literature"].

PMID- 8303585
TI  - [Curative therapy in the presence of distant metastases. On the paper by H.
      Hawighorst et al. Cure in a patient with multiple osseus metastases in non-small
      cell lung cancer: a case report].

PMID- 8303586
TI  - [Painless ischemia in the acute period of myocardial infarct].
AB  - The examination of 119 patients with primary acute macrofocal myocardial
      infarction included 24-hour monitoring to detect episodes of painful or painless
      ischemia. Three groups of patients were identified: 55 subjects with both painful
      and painless ischemia, 39 subjects with painless ischemia and 25 patients without
      ischemia. Diastolic and systolic functions of the left ventricle were assessed at
      Doppler echocardiography in all the patients who were followed up for 1 year. It
      was found that painless ischemia revealed early in myocardial infarction affects
      negatively left ventricular systolic and diastolic functions thus strongly
      suggesting an unfavorable short-term prognosis.

PMID- 8303587
TI  - [The detection of preventive hypofibronectinemia in diagnosing the development of
      disseminated intravascular coagulation in patients with myocardial infarction at
      the hospital rehabilitation stage].
AB  - Postmyocardial infarction patients on hospital rehabilitation in case of no
      complications were examined for time course changes in the levels of fibrinogen
      degradation products (FDP), free hemoglobin (fHg) and fibronectin (Fn) using
      enzyme immunoassay. As shown by FDP and fHg values, the patients had DIC syndrome
      with its maximum on observation days 6-12 and 22-24. Fn fall occurred on the
      disease day 2-4 preceding maximum hemostasis activation up to 6-12th day. Less
      marked Fn reduction on the disease day 15-17 predicted a rise in hemocoagulation
      on day 22-24. It is recommended to determine FDP, fHg and Fn levels in blood of
      postmyocardial infarction patients to detect DIC syndrome and prevent hemostasis
      activation.

PMID- 8303588
TI  - [Left ventricular function in patients with arterial hypertension and myocardial
      hypertrophy based on the data of multiphasic ventriculography].
AB  - The study included 39 hypertensive subjects with clinical echocardiographic
      evidence of left ventricular hypertrophy. All the patients were subjected to
      coronary angiography and transvenous multiple-phase left ventriculography. Early
      subclinical signs of left ventricular dysfunction in hypertensive patients have
      been defined. They concern energetic efficacy of the cardiac cycle, left
      ventricular diastolic function, myocardial asynchronism. It is noted that the
      above dysfunction was recorded in cases where standard two-image analysis
      provides normal values.

PMID- 8303590
TI  - [Preventing cardiovascular diseases--one of the most pressing problem in Russian
      medicine].

PMID- 8303589
TI  - [Evaluation of the effect of Isoptin-Retard on central hemodynamics and
      parameters of diastolic ventricular function in patients with hypertension].
AB  - A short treatment course (2-3 weeks) of calcium antagonist isoptin-retard has
      been tried in 20 patients with stable essential hypertension stage II-III. The
      treatment achieved: clinical response in the majority of the patients in the
      presence of minor prolongation of the atrioventricular conduction, a clear
      tendency to reduction of systolic, mean arterial and resting diastolic pressures.
      Stroke volume increased both at rest and under loading, peripheral resistance of
      the vessels diminished, maximum filling rate for the left ventricle increased,
      its peak was reached more rapidly, hemodynamic contribution of the first third
      diastole to left ventricular filling rose against less contribution of the left
      atrial systole. Thus, it is shown that isoptin-retard in a mean dose 420 mg/day
      demonstrates hypotensive activity and beneficial hemodynamic effects without
      pronounced increase in atrial-ventricular conduction in hypertensive subjects
      with the disease stage II-III.

PMID- 8303591
TI  - [Evaluation of the efficacy and tolerance of the new delayed-action angiotensin
      converting enzyme inhibitor cilazapril in patients with hypertension (preliminary
      report)].
AB  - Cilazapril [correction of Silazapril], a new inhibitor of long-acting angiotensin
      converting enzyme, was given to 39 hypertensive subjects aged 24-68 with initial
      diastolic pressure 95-120 mm Hg. Of them 16 were females and 23 were males. The
      course of the treatment lasted 8 weeks, the drug being taken daily in a single
      dose 2.5 mg in the morning. Checkups, measurements of arterial pressure (AP),
      blood counts, urinalyses were made before the treatment, on the treatment week 4
      and 8. In one patient the drug was discontinued 4 weeks after the treatment start
      because the AP fall to 110/63, in 23 patients the dose was raised to 5 mg, the
      rest continued on 2.5 mg/day. The treatment ended in the systolic pressure
      decrease by 14.9% (from 161.0 +/- 2.9 to 137.8 +/- 2.8 mm Hg, p < 0.0001) and
      diastolic pressure fall by 13.5% (from 104.5 +/- 1.4 to 90.1 +/- 1.7 mm Hg, p <
      0.005). No side effects causing the drug withdrawal were registered. It is
      concluded that the drug is effective in essential hypertension stage IIA-IIB as
      monotherapy.

PMID- 8303592
TI  - [The problem of tolerance to nitrates and the means to resolve it in patients
      with exertional stenocardia].
AB  - The problem of nitrates tolerance and resistance has been studied for 10 years in
      a number of clinical pharmacological cross-over studies in patients with stable
      angina of effort by specially devised pharmacodynamic and pharmacokinetic
      methods. Both single doses in different medicinal forms and long-term course
      intake of nitrates were investigated. The results led the authors to the
      following conclusions: 1) tolerance to isosorbide dinitrate arises in 58% of the
      patients for 6-12 weeks under regular administration of the drug; 2) transdermal
      nitroglycerin (nitroderm) and in a less degree oral sustak under long-term
      treatment regimens become tolerable, whereas a buccal form (trinitrolong) secures
      a prolonged stable effect; 3) tolerance develops in 2-month administration of
      oral isosorbide-5-mononitrate; 4) donors of SH-group (methionine) and inhibitors
      of angiotensin-converting enzyme with SH-group and without it (captopril and
      perindopril, respectively) in single doses potentiate an antianginal effect of
      isosorbide dinitrate (even in initial resistance to nitrate), being ineffective
      in its absence; 5) molsidomine is promising in long-term regimens as an
      antianginal drug alternative to nitrates.

PMID- 8303593
TI  - [Debatable questions in chronic heart failure].

PMID- 8303594
TI  - [Incidence and pathomorphological characteristics of the development of sudden
      coronary death in coal miners].
AB  - The authors studied autopsy protocols, microscopic and histochemical data on the
      heart for miners who had died suddenly. No positive trend in the sudden coronary
      death incidence in miners was reported. A great number of sudden deaths were
      registered in mines. The deaths are attributed to severe atherosclerosis
      responsible for irreversible changes in the myocardium, coronary vascular spasms,
      emergence of pathological agitation triggering lethal ischemia.

PMID- 8303595
TI  - [Effect of long-term monotherapy with propranolol and nifedipine on the quality
      of life and psychological status of patients with hypertension].
AB  - WHO criteria of quality of life and psychological status were employed in a
      randomized placebo-controlled cross-over trial of relevant effects induced by
      propranolol and nifedipine. Forty patients with essential hypertension (EH) stage
      I-II aged 35-60, males with diastolic pressure 96-114 mm Hg, entered the trial.
      Monotherapy with calcium antagonist nifedipine produced a beneficial effect on EH
      patients' quality of life, they became more sociable and active. Propranolol,
      beta-adrenoblocker, given for 4 weeks resulted in psychosocial dysadaptation,
      hypochondriasis, depressions. It is concluded that an antihypertensive effect of
      the above drugs was related to the EH patients' initial status: one can predict
      psychological benefit of nifedipine in patients without neurotic symptoms, while
      propranolol is more effective in neurotic EH subjects.

PMID- 8303596
TI  - [Hypotensive effect and characteristics of the effect on the central hemodynamics
      of the delayed-action form of diltiazem (Dilren) in patients with hypertension].
AB  - Calcium antagonist dilren in a short course was given to 11 hypertensive subjects
      (AH stage II). A clinical response in the majority of the patients was associated
      with a decline in systolic, mean arterial and resting diastolic pressure (by 8.1,
      7.8 and 11.5%, respectively). In orthostasis and under isometric loading dynamic
      values of arterial pressure tended to lowering, especially diastolic (by 6.7 and
      8.3%, respectively). Reduced pressure resulted from a significant reduction in
      the total peripheral resistance (by 19.8% at rest, in orthostasis by 10%, in
      isometric load by 26.1%). Minute blood volume increased because of a rise in
      stroke output. Dilren is recommended in a standard dose 300 mg/day in mild
      hypertension and in an individual dose 600 mg/day in moderate disease.

PMID- 8303597
TI  - [Isoptin-Retard 240 mg in the treatment of mild and moderate arterial
      hypertension].
AB  - To elucidate a hypotensive effect of isoptin-retard in a dose 240 mg/day, 17
      males with mild and moderate hypertension receiving the drug underwent 24-h
      monitoring by SpaceLabs 5300 and pressure loading. A significant lowering of both
      mean systolic and diastolic pressure was found both in daytime and at night. A
      hypotensive effect persisted for 2 months. No case of serious cardiovascular
      complications, of noticeable shifts in blood biochemistry was reported.

PMID- 8303598
TI  - [Clinical and blood rheologic effects of ticlid in patients with cerebrovascular
      diseases].
AB  - Clinical efficacy of tiklid in a dose 500 mg/day and its action on platelet
      vascular hemostasis were evaluated in 24 patients with cerebrovascular diseases.
      A 15-day tiklid course promoted a regress in some subjective symptoms (headache,
      vertigo, walking instability, photopsias, etc.), the objective neurological
      status being unchanged. Tiklid had a positive influence on some rheological
      parameters and platelet vascular hemostasis. ADP-induced platelet aggregation,
      blood fibrinogen levels got reduced. The platelets sensitivity to antiaggregation
      agent PgI2 in vitro arose. Antiaggregation potential of the vascular wall
      returned to normal in 33% of patients with initially low or inverse response.

PMID- 8303599
TI  - [Reperfusion arrhythmias: mechanisms of development and means of correction].

PMID- 8303600
TI  - [Infectious endocarditis in middle-aged and elderly patients].
AB  - The analysis is presented of clinical picture, running, therapy and prognosis of
      infectious endocarditis in 67 patients over 60. They appeared to develop
      progressive cardiac failure, frequent thromboembolism of the cerebral vessels.
      The disease is often associated with other age-related disorders, proved
      difficult for differential diagnosis. Elderly patients show resistance to
      antibacterial therapy more frequently and have worse prognosis for endocarditis
      outcome.

PMID- 8303601
TI  - [Evaluation of the severity of aortic stenosis using 2-dimensional Doppler
      echocardiography].
AB  - Hemodynamic evaluation of aortic ostial stenosis (AOS) was made in 89 patients at
      Doppler echocardiography. Maximal circulation rate (MCR) through the aortic valve
      averaged 3.47 +/- 0.073 m/s, maximal transaortic pressure gradient (TPG) made up
      49.97 +/- 2.11 mm Hg, the aortic ostium area (AOA) amounted to 0.85 +/- 0.031
      sm2. It was established that AOA evaluation is most reasonable, as MCR and TPG
      vary with cardiac output. Especially desirable this measurement is believed in
      patients with TPG under 64 mm Hg and small left ventricular ejection. Mitral
      regurgitation is a frequent finding in AOS patients. Unless calcinosis of the
      mitral ring, mitral valve affection would be absent. In mitral regurgitation the
      disease took a more severe course, the patients having reduced AOA and left
      ventricular ejection, though larger end-diastolic diameter and end-diastolic
      volume. The emergence of mitral regurgitation in AOS is a result of left
      ventricular hypertrophy and dilatation suggesting a low compensatory reserve of
      the myocardium.

PMID- 8303602
TI  - [Experience with the use of standardized inference in Doppler echocardiographic
      study].
AB  - The authors propose a scheme for the inference on the results of ultrasonic
      cardiovascular investigation in cardiological patients. The scheme for putting
      into the computer has been developed in the A. N. Bakulev Institute for
      Cardiovascular Surgery. Its introduction improved the diagnosis, allowed
      monitoring of the follow-up examinations with comparison of the results in
      different patients as well as statistical processing of the findings and making
      diverse calculations. The programs designed imply the work of an operator whom
      should be a specially trained physician in the department of ultrasonic
      diagnosis.

PMID- 8303603
TI  - [Problems in the classification of chronic heart failure].

PMID- 8303604
TI  - [Adaptive and non-adaptive reactions of central hemodynamics to conditions of
      heat discomfort].
AB  - Chest rheography was used to study central hemodynamics in 134 healthy males aged
      18-28 in comfortable weather conditions and discomfortable ones, that is at
      equivalent-effective temperature 17-24 degrees C and above 27-30 degrees C,
      respectively. In trained subjects from native and non-native population under
      comfortable weather conditions heart rate (HR) proved to be significantly reduced
      as compared to untrained subjects (57.6 +/- 1.1 and 56.2 +/- 1.2 against 73.9 +/-
      1.7 and 70.4 +/- 0.9), whereas stroke volume in trained males was significantly
      larger (by 14.2 and 14.0%, respectively). Minute blood volume (MBV), cardiac and
      stroke indices, systolic and diastolic pressure showed no significant
      differences. Heat discomfort gave rise to a slow-pulse trend in trained subjects
      from both native and non-native populations, in untrained subjects, especially
      non-natives heart rate accelerated. MBV increased in trained native and non
      native examinees by 11.0 and 11.1%, respectively, while in untrained natives the
      rise reached 17.2%. This was secured by stroke volume elevation by 14.3, 10.7 and
      11.2%, respectively (p < 0.05), in non-natives by acceleration of heart rate by
      11.2%. A trend to lowering of arterial pressure was more marked in untrained
      examinees of both populations. It is evident that in conditions of arid zone heat
      discomfort trained subjects from both native and non-native populations exhibited
      adequate hemodynamic responses, whereas strain was observed in circulatory system
      functioning when it adapted to heat discomfort in untrained non-natives.

PMID- 8303605
TI  - [Clinical aspects of amlodipine pharmacokinetics].

PMID- 8303606
TI  - [Results of using Aredia for hypercalcemia in oncology patients].

PMID- 8303607
TI  - [Hydroxyurea in the treatment of erythremia].

PMID- 8303608
TI  - [Aleksandr Leonidovich Miasnikov (fragments of reminiscences)].

PMID- 8303609
TI  - Surprising statement is made that the causes of coarctation of the aorta are
      almost entirely unknown.

PMID- 8303610
TI  - Effect of in utero exposure to diagnostic ultrasound on the postnatal survival
      and growth of mouse.
AB  - Pregnant Swiss albino mice were exposed to 3.5 MHz diagnostic ultrasound for 10
      min (upper limit for ISPTP = 1 W/cm2 and for ISATA = 240 mW/cm2, acoustic power =
      approximately 65 mW) on day 3.5 (preimplantation period), 6.5 (early
      organogenesis period), 11.5 (late organogenesis period), or 14.5 (early fetal
      period) of gestation. The offspring were observed for changes in litter size at
      birth, and sex ratio at 4 weeks of age, and postnatal mortality and growth
      retardation up to 6 weeks of age. No significant difference from control in
      litter size or sex ratio was observed in the offspring exposed to ultrasound on
      any of the gestation days studied. Exposure at the early organogenesis period
      produced a marginally significant increase in the postnatal mortality. A
      significant number of ultrasound exposed animals showed lesser body weights than
      the control group. However this growth retardation was transient and the normal
      growth pattern was restored by 6 weeks of age. It is concluded that the early
      stages in mouse gestation may be sensitive to the lethal effects of ultrasound
      than the later stages of pregnancy. Even though a small increase in the postnatal
      mortality was observed in the ultrasound exposed animals, the normal growth was
      not affected in the surviving animals except for a transient growth retardation.
      Low birth weight may be a characteristic effect of exposure only at the
      preimplantation period.

PMID- 8303611
TI  - Facial features of infants exposed prenatally to cocaine.
AB  - Thirty two infants referred for in-patient genetics evaluation at the University
      of California at San Francisco, 1987-1992, were found to have a history of
      maternal cocaine use. Genetics reports and medical records were reviewed on all
      these infants to identify features distinctive for cocaine exposure. Among these
      32 cases, 14 infants were exposed only to cocaine; 18 were exposed to alcohol and
      cocaine. The infants evaluated displayed a distinctive phenotype, consisting of
      neurologic irritability, large fontanels, prominent glabella, marked periorbital
      and eyelid edema, low nasal bridge with transverse crease, short nose, lateral
      soft tissue nasal buildup, and small toenails. Features consistent with the fetal
      alcohol syndrome appeared distinct and coexistent with the other described facial
      findings. Other severe abnormalities included cleft lip/palate, atypical facial
      cleft, abnormal BSER, intraventricular hemorrhages, arthrogryposes, and
      genitourinary abnormalities. Forty percent of the infants were born prematurely;
      28% were small for gestational age; 43% showed head circumference values less
      than the 10th percentile. We conclude that these findings may be distinctive for
      a diagnosis of fetal cocaine syndrome; such findings should be further
      established by a future blinded prospective study of mothers and neonates.

PMID- 8303612
TI  - In vitro embryotoxicity of N-methyl-N-(7-propoxynaphthalene-2-ethyl)hydroxylamine
      (QAB): evidence for N-dehydroxylated metabolite as a proximate dysmorphogen.
AB  - The rat conceptus biotransforms N-methyl-N-(7-propoxynaphthalene-2
      ethyl)hydroxylamine (QAB) in vitro to 7-propoxynaphthalen-2-ylacetic acid (QAA)
      and six more (M1 to M6) metabolites. Thus far, M4 has been identified as N
      demethyl-QAB and M6 as N-desoxy-QAB. We investigated which of these two
      metabolites might be involved in QAB-embryotoxicity in vitro. Conceptuses were
      cultured from day 9.5 to 11.5 post-coitum, and were exposed to N-demethyl-QAB or
      N-desoxy-QAB either in the culture medium or by microinjection directly into the
      amniotic cavity. When added to the culture medium, N-demethyl-QAB (No Observed
      Adverse Effect Level, NOAEL, for growth 122 microM and for differentiation 41
      microM) was less active than QAB itself (NOAEL for growth and differentiation 12
      microM). N-desoxy-QAB caused severe growth retardation and an impairment of
      differentiation at a concentration of 11 microM (NOAEL 3.6 microM). As regards
      causing anomalies, the NOAEL of N-demethyl-QAB (41 microM) was 10-fold higher
      than that of QAB (NOAEL 3.9 microM) and that of N-desoxy-QAB (NOAEL 3.6 microM).
      At an intraamniotic concentration of 0.7 mM, N-demethyl-QAB caused no effects on
      growth and differentiation and no increase of anomalies was observed, whereas QAB
      and N-desoxy-QAB each elicited an increase in dysmorphogenic embryos at equimolar
      concentrations without affecting growth and differentiation. It is, therefore,
      concluded that N-desoxy-QAB, but not N-demethyl-QAB, could be a proximate
      dysmorphogen responsible for the embryotoxicity/teratogenicity of QAB in vitro.

PMID- 8303613
TI  - Descriptive epidemiology of small intestinal atresia, Atlanta, Georgia.
AB  - To describe the epidemiology of small intestinal atresia (SIA) in Atlanta,
      Georgia, from 1968 through 1989, we used the Metropolitan Atlanta Congenital
      Defects Program, an active, population-based surveillance system for birth
      defects diagnosed during the first year of life. We identified 176 infants with
      SIA, a prevalence of 2.8 per 10,000 livebirths. Among black infants, the
      prevalence was 3.7 per 10,000 livebirths, significantly higher than the
      prevalence of 2.4 per 10,000 among white infants [relative risk (RR) = 1.6, 95%
      confidence interval (CI) = 1.1,2.1]. Nine infants were each one member of a
      unique pair of twins. The prevalence among twin infants was 7.3 per 10,000,
      significantly higher than the prevalence of 2.8 per 10,000 among singletons (RR =
      2.7, 95% CI = 1.4,5.2). Forty-nine percent of the infants had duodenal atresia,
      36% had jejunal atresia, and 14% had ileal atresia. Two infants (1%) had atresia
      at an unspecified site in the small intestine. We grouped the infants by anatomic
      location of SIA into four categories: isolated SIA (53%), SIA with multiple
      unrelated defects (21%), sequences (16%), and syndromes (10%). We then compared
      the isolated and multiple unrelated defects groups by gender, race, maternal age,
      birth weight and one-year mortality for each location of SIA. Among black infants
      the prevalence of isolated jejunal atresia was 1.4 per 10,000, significantly
      higher than the prevalence of 0.2 per 10,000 among white infants (RR = 6.3, 95%
      CI = 2.9, 13.5). The increased prevalence of these defects among twins was a
      particularly interesting finding.

PMID- 8303614
TI  - Effects of low level prenatal 60Co gamma-irradiation on postnatal growth and
      behavior in mice.
AB  - Pregnant Kun Ming strain mice were exposed to a total dose of 0, 0.1, 0.2, or 0.4
      Gy from 60Co gamma-rays from the 13th to the 18th days of gestation. An overall
      delay of the appearance of two physiologic markers (pinna detachment, eye
      opening) and the age of acquisition of four reflexes (surface righting, air
      righting, auditory startle, visual placing) was observed in offspring exposed to
      0.2 or 0.4 Gy in utero. Postnatal growth retardation, shortened length of hanging
      time, inhibited exploratory activity in the hole board test (decreased number of
      head-dipping), and hyperactivity in the open field test (shortened latency to
      leave the center area and increased number of squares entered) were also found
      among the offspring exposed to 0.2 Gy or more in utero. The results indicate that
      0.1-0.2 Gy may represent a threshold range in mice for certain physiologic and
      behavioral effects resulting from continuous exposure to 60Co gamma-rays on the
      13th-18th days of gestation.

PMID- 8303615
TI  - Histological study of the cranial neural folds of mice genetically liable to
      exencephaly.
AB  - The SELH/Bc (SELH) inbred stock of mice has a high liability to the neural tube
      closure defect, exencephaly. All SELH embryos close their cranial neural tubes by
      an abnormal mechanism, lacking elevation and initiation of fusion in the
      posterior prosencephalon/anterior mesencephalon region. Most embryos complete
      closure of the cranial neural tube by extension of a more rostral site of fusion,
      but in 10-20% this process fails, and the embryos are subsequently exencephalic.
      In this study, transverse histological sections of the cranial neural folds of
      SELH embryos at the 3-5, 6-8, and 9-11 somite stages were compared to those of
      two strains with normal neural tube closure, ICR/Bc and LM/Bc. At all stages,
      consistent morphological differences were observed between SELH and the two
      normal strains. In 3-5 somite SELH embryos, the divergence of the folds from the
      neural groove is more angular, the folds are flatter, and their lateral tips
      appear "hooked" downward. In 6-8 somite SELH embryos, the lateral tips of the
      folds appear more elongated and in the prosencephalon they are less elevated than
      in the normal strains. The boundary between neuroepithelium and mesenchyme or
      surface ectoderm tends to be less clear than normal in SELH lateral tips. In 9-11
      somite SELH embryos, divergence of the folds from the neural groove continues to
      be angular and the lateral folds are splayed horizontally. In addition, the
      lateral surface ectoderm is abnormally indented and the neuroepithelium/surface
      ectoderm boundary is more ventral and lateral in SELH than in ICR/Bc and LM/Bc.
      The hypothesis that the defect in SELH cranial neural folds might involve the
      cytoskeleton was tested using a fluorescent probe for filamentous actin in 7
      somite SELH and ICR/Bc embryos. The actin staining pattern in SELH embryos was
      like that of normal ICR/Bc embryos, with a strongly staining apical concentration
      in the neuroepithelium. This suggests that there is no gross cytological
      abnormality within the neuroepithelium, but does not rule out more subtle
      defects, such as those involving cytoskeletal function.

PMID- 8303616
TI  - 33rd Annual Meeting of the Japanese Teratology Society. Nagoya, Japan, July 21
      23, 1993. Abstracts.

PMID- 8303617
TI  - What a nurse should know about layoffs and workplace redesign.

PMID- 8303618
TI  - Legal issues for nurses. Liability issues for nurse educators.

PMID- 8303619
TI  - Texas AIDS facts.

PMID- 8303620
TI  - Leukotrienes and aspirin induced asthma.

PMID- 8303621
TI  - HIV in the lung: guilty or not guilty?

PMID- 8303622
TI  - Vasodilators in pulmonary hypertension.

PMID- 8303623
TI  - Out of the mouths of babes and sucklings: lessons from early childhood asthma.

PMID- 8303624
TI  - Effect of the leukotriene receptor antagonist MK-0679 on baseline pulmonary
      function in aspirin sensitive asthmatic subjects.
AB  - BACKGROUND: The cysteinyl leukotrienes (LTC4, LTD4, and LTE4) have been shown to
      mediate airway obstruction evoked by several factors which trigger asthmatic
      reactions--for example, allergen and exercise. Accordingly, drugs which block the
      action or formation of these leukotrienes are being evaluated as a new treatment
      of asthma. Elevated production of leukotrienes has been reported in asthmatic
      subjects who are intolerant to aspirin and related nonsteroidal anti-inflammatory
      drugs. In this study the influence of the specific leukotriene receptor
      antagonist MK-0679 was tested on basal airway function in asthmatic patients with
      documented aspirin intolerance. METHODS: The eight subjects in the study had a
      mean baseline FEV1 of 78% predicted (range 58-99%) and six required treatment
      with inhaled glucocorticosteroids (400-1200 micrograms budesonide/beclomethasone
      daily). On two separate days the subjects received either 825 mg MK-0679 or
      placebo, orally in a double blind, randomised, crossover design. RESULTS: The
      leukotriene antagonist MK-0679 caused bronchodilation which lasted for at least
      nine hours. The average peak improvement in FEV1 was 18% above the predrug
      baseline, but the bronchodilator response varied between 34% and 5% and was found
      to correlate strongly with the severity of asthma and aspirin sensitivity.
      CONCLUSIONS: The findings indicate that ongoing leukotriene production may be one
      cause of persistent airway obstruction in aspirin sensitive asthmatic subjects
      and that they may benefit from treatment with a leukotriene receptor antagonist.

PMID- 8303625
TI  - How many times per day should peak expiratory flow rates be assessed when
      investigating occupational asthma?
AB  - BACKGROUND: Serial peak expiratory flow rate (PEF) recording has been advocated
      as a sensitive and specific means of confirming work related asthma. The optimum
      number of recordings per day to achieve the best between-reader and within-reader
      reproducibility and sensitivity/specificity ratio compared with the final
      diagnosis determined by specific inhalation challenges is unknown. METHODS: PEF
      recording was carried out every two hours in 74 subjects referred for possible
      occupational asthma. Specific inhalation challenges performed in a hospital
      laboratory or at the workplace (positive in 33 subjects and negative in 41) were
      considered the gold standard. The duration of monitoring at work and away from
      work was at least two weeks each. Graphs of PEF recordings were generated in four
      different ways: every two hours, four times/day, three times/day, and every
      morning and evening. The graphs were assessed by three readers in three different
      centres in a blind manner. Furthermore, one third of each type of graph was read
      blind by the same reader one week after the initial interpretation. RESULTS:
      Agreement between the three readers was a little more frequent (82%) in the case
      of the every two hour readings than for the other types of readings (70% v 77%).
      Agreement between at least two of the three readers occurred in 73% of positive
      challenges (sensitivity) and in 78% of negative challenges (specificity) for
      every two hour readings. The figures varied from 61% to 70% for positive
      challenges and from 78% to 88% for negative challenges for the other types of
      readings. Within-subject reproducibility from one reading to the next (one week
      apart) was excellent (83% to 100%). CONCLUSIONS: Recording PEF every two hours
      results in a slightly more satisfactory agreement between readers and in
      concordance in terms of sensitivity/specificity than less frequent PEF readings,
      although the four times a day assessment is almost as satisfactory.

PMID- 8303626
TI  - Is exercise testing useful in a community based asthma survey?
AB  - BACKGROUND: In hospital clinics exercise challenge is used as a simple, non
      invasive, non-pharmacological test for asthma in childhood. Little is known of
      its value in a community setting. An exercise test was therefore evaluated as an
      adjunct to a respiratory questionnaire in the course of an asthma survey.
      METHODS: From a cohort of 4003 primary school children, 607 of 799 with
      respiratory symptoms answered a detailed respiratory questionnaire. From the same
      cohort 135 of 229 randomly selected asymptomatic children were also interviewed.
      A stratified selection of one in four of the children interviewed was then
      invited to take part in a six minute cold air enhanced exercise challenge test;
      128 symptomatic and 26 asymptomatic children attended. RESULTS: Bronchial
      hyperreactivity, a fall of FEV1 > or = 10% at five, 10, or 15 minutes following
      the exercise challenge, was identified in 15 of 128 symptomatic children and in
      one of 26 asymptomatic children. Bronchial hyperreactivity was found in only one
      of three children with frequent shortness of breath and one of five with frequent
      wheeze. It was found in 13 of 58 children whose parents were aware of the
      diagnosis of asthma; in 10 of 26 children who were on regular prophylactic
      treatment; in only 11 of 70 children with a history of exercise induced symptoms;
      and seldom in children with mild symptoms. Gestational age and ventilator support
      in the neonatal period were significant predictors of bronchial hyperreactivity.
      CONCLUSIONS: Exercise testing enhanced by cold air adds very little to a well
      designed respiratory questionnaire in community studies of asthma in childhood.

PMID- 8303627
TI  - Relation of HIV-I in bronchoalveolar lavage cells to abnormalities of lung
      function and to the presence of Pneumocystis pneumonia in HIV-I seropositive
      patients.
AB  - BACKGROUND: HIV is present in bronchoalveolar lavage cells of some but not all
      HIV seropositive patients. Abnormalities of lung function have been described in
      such patients in the absence of clinically overt pneumonia or other respiratory
      infections. It is possible that the presence of HIV in alveolar macrophages could
      account for these abnormalities. It is also possible that the presence of HIV in
      alveolar macrophages contributes to immunosuppression and an increased incidence
      of opportunistic infections. METHODS: This was a prospective study of 157 HIV
      seropositive patients requiring diagnostic bronchoscopy for investigation of new
      respiratory symptoms, chest radiograph abnormality, or pneumonic illness.
      Presence of HIV in bronchoalveolar lavage cells obtained at diagnostic
      bronchoscopy was determined by polymerase chain reaction to detect proviral DNA
      and in vitro cocultivation to detect productive virus infection. With these two
      techniques the presence or absence of HIV in bronchoalveolar lavage was compared
      with the presence of abnormalities of lung function or presence of Pneumocystis
      pneumonia. RESULTS: HIV was detected in bronchoalveolar lavage cells in 65% of
      patients by means of the polymerase chain reaction and 59% with cocultivation.
      With both methods of detection there was no association between the presence or
      absence of HIV and the presence of Pneumocystis pneumonia; nor was there a
      relation between the presence of HIV and abnormalities of lung function.
      CONCLUSION: The presence of HIV in bronchoalveolar lavage cells does not
      predispose to an increased incidence of Pneumocystis pneumonia; nor does it
      contribute to abnormalities of lung function.

PMID- 8303628
TI  - Value of bacterial antigen detection in the diagnostic yield of transthoracic
      needle aspiration in severe community acquired pneumonia.
AB  - BACKGROUND: Transthoracic needle aspiration (TNA) with an ultrathin needle is a
      safe and highly specific procedure for obtaining a diagnosis in bacterial
      pneumonias, but its sensitivity is at best 70%. A study was performed to assess
      whether Streptococcus pneumoniae and Haemophilus influenzae type b antigen
      detection by latex agglutination from the TNA sample enhanced the diagnostic
      yield. METHODS: Blood cultures, TNA with an ultrathin needle (culture, Gram
      stain, and latex agglutination), serological tests, and pneumococcal antigen
      detection in the urine by counterimmunoelectrophoresis were performed in samples
      from 18 of 23 consecutive patients with severe community acquired pneumonia.
      RESULTS: The causative organism was identified in 16 cases (88%): S pneumoniae
      (10 cases), S pneumoniae plus H influenzae (two cases), Legionella pneumophila
      (three cases), and Mycoplasma pneumoniae (one case). The investigation of
      antigens by latex agglutination in the pulmonary aspirate increased the
      diagnostic yield of TNA from 50% to 78% and provided a rapid diagnosis (in less
      than two hours) with therapeutic implications in seven cases. Its effectiveness
      was not modified by prior antibiotic therapy. CONCLUSIONS: A latex agglutination
      test on the pulmonary aspirate enhances the diagnostic yield of TNA in severe
      community acquired pneumonia.

PMID- 8303629
TI  - Correlation of GM-CSF mRNA in bronchoalveolar fluid with indices of clinical
      activity in sarcoidosis.
AB  - BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) has several
      proinflammatory effects, some of which potentially favour granuloma formation.
      Its mRNA expression by the inflammatory cells recovered from lungs of patients
      with pulmonary sarcoidosis has been previously reported. In this study an
      association between GM-CSF expression and manifestations of the disease was
      explored. METHODS: GM-CSF mRNA was detected by reverse transcription polymerase
      chain reaction in the cells of bronchoalveolar lavage (BAL) fluid of 20 patients
      with pulmonary sarcoidosis. RESULTS: GM-CSF mRNA expression was positive in 15 of
      20 patients with sarcoidosis. Fourteen of the 15 patients with positive mRNA
      expression had worsening or unchanged disease during the year preceding this
      study, on the basis of radiographic or physical findings, or both, whereas all
      five "negative" patients were judged to be improving. Similarly, serum levels of
      angiotensin converting enzyme, the proportion of lymphocytes in BAL fluid, and
      the CD4+/CD8+ ratio of lymphocytes in BAL fluid were significantly higher in the
      positive patients. CONCLUSIONS: There was an association between the presence of
      GM-CSF mRNA in the cells in BAL fluid and other indices of disease activity in
      sarcoidosis.

PMID- 8303630
TI  - Kinetics and cellular localisation of putrescine uptake in human lung tissue.
AB  - BACKGROUND: The polyamines (putrescine, spermidine, and spermine) are involved in
      cellular growth, proliferation, and differentiation. In the lungs of various
      species, polyamines are accumulated by an active uptake system which also
      mediates the uptake of cystamine and paraquat. In the rat lung putrescine uptake
      has been shown to be cell-specific, occurring predominantly in the alveolar
      epithelium. The aim of this study was to characterise the uptake of putrescine in
      human lung. METHODS: Lung tissue was obtained from 31 patients undergoing surgery
      for lung cancer. Slices (0.7 mm thick) from non-tumour containing lung parenchyma
      were incubated for 15-60 minutes in Krebs-Ringer phosphate buffer with various
      concentrations of putrescine (2.5 to 80 mumol/l) containing 0.1 microCi [1,4-14C]
      putrescine. Uptake was assessed from tissue radioactivity. For autoradiographic
      imaging, slices were incubated for 30 minutes with 2.5 mumol/l putrescine
      containing 2.5 mCi [1,4n-3H]-putrescine. RESULTS: The accumulation of [14C]
      putrescine into slices was time-dependent and energy-dependent, and obeyed
      saturation kinetics, with mean calculated values for Vmax (maximal rate of
      uptake) of 414 nmol/g/hour and for Km (medium concentration at which the rate of
      uptake is half Vmax) of 7.2 mumol/l, with a large interindividual variation.
      Competitive inhibition was observed on incubation with cystamine, which appears
      to have a high affinity for the uptake system since its calculated Ki
      (concentration of inhibitor at which the Km is doubled) was 3.2 mumol/l.
      Ultrastructural autoradiography showed labelling over both type I and type II
      cells of the alveolar epithelium, but not over the endothelium or any cells of
      the interstitium. Alveolar macrophages were also devoid of label. CONCLUSIONS:
      These results show that the human lung possesses an active uptake system for
      putrescine, and probably also cystamine, which is located in both cell types of
      the alveolar epithelium. These findings may be used to develop tests for the
      assessment of the alveolar epithelium.

PMID- 8303631
TI  - Identification of sleep disruption and sleep disordered breathing from the
      systolic blood pressure profile.
AB  - BACKGROUND: Respiratory sleep studies are frequently performed to identify sleep
      disruption resulting from upper airway obstruction. Traditional polysomnographic
      studies may not detect brief recurrent sleep disruption and thus fail to
      recognise a significant problem when apnoea, hypopnoea, or arterial desaturation
      are not present. Arousal from sleep causes a transient blood pressure rise, and
      each inspiration causes a transient blood pressure fall. This study assesses
      whether these blood pressure changes are a useful indirect marker of disturbed
      sleep, obstructed sleep apnoea, and snoring related sleep disturbance. METHODS:
      Computer algorithms were developed to identify blood pressure falls caused by
      inspiration and rises related to arousal from 286 sleeping blood pressure samples
      of a consistent respiratory state drawn from 51 polysomnographic studies. From
      these samples, normal ranges for the number of arousal related systolic rises and
      the average size of the inspiratory falls were established. These were then
      applied prospectively to all night unedited blood pressure recordings from a
      further 20 subjects. RESULTS: The size of the inspiratory falls in blood pressure
      progressively increased from normal sleep, through snoring, to frank obstructive
      sleep apnoea. The 95th centile of normal was 12.5 mm Hg. The number of arousal
      related blood pressure rises also increased during obstructive sleep apnoea and
      periods of snoring with associated arousals, compared with normal undisturbed
      sleep, and all these periods of disturbed sleep included more than 30 such rises
      per hour. When these blood pressure features were examined in the 20 subjects
      studied prospectively, the six with a sleep related breathing disorder could all
      have been identified from their systolic blood pressure profile alone.
      CONCLUSIONS: The systolic blood pressure profile may be helpful in identifying
      patients with obstructive sleep apnoea, snoring with arousals, or other sleep
      disruption syndromes.

PMID- 8303632
TI  - Investigation and management of pulmonary infiltrates following bone marrow
      transplantation: an eight year review.
AB  - BACKGROUND: Although pulmonary infiltrates are common in bone marrow transplant
      recipients and add significantly to the morbidity and mortality of this group of
      patients, there is uncertainty as to the most appropriate investigation and a
      lack of information on the effects of investigations on management and outcome.
      METHODS: All bone marrow transplant recipients from one institution referred for
      respiratory investigation between 1982 and 1990 were reviewed. RESULTS: Of 204
      bone marrow transplant recipients 27 developed pulmonary infiltrates which failed
      to respond to broad spectrum antibiotics. All were examined by bronchoscopy and
      bronchoalveolar lavage. A specific diagnosis was made in 20 cases, 17 with an
      infective cause and three with a non-infective aetiology. In 17 of the 27
      episodes these investigations led to a positive change in treatment, but in only
      five did these changes result in patient survival beyond one month. Eighteen of
      the 20 deaths were due to progressive respiratory failure of an infective
      aetiology in 14 and non-infective in four. CONCLUSIONS: Bronchoscopy and
      bronchoalveolar lavage are effective in establishing a diagnosis, but the impact
      on overall survival is disappointingly poor.

PMID- 8303633
TI  - Endocrine cells in diffuse pulmonary fibrosis.
AB  - BACKGROUND: There is evidence to suggest, particularly from studies in animals,
      that the products of pulmonary endocrine cells, especially gastrin releasing
      peptide, may have a role in the pathogenesis of fibrosis in the lung. This study
      was carried out to examine the morphology, number, distribution, and content of
      pulmonary endocrine cells in tissue from 49 patients with diffuse pulmonary
      fibrosis. METHODS: Twenty patients with interstitial pneumonitis, 17 with early
      fibrosis, and 12 with frank honeycombing were studied, together with five age
      matched controls without pulmonary disease. Endocrine cells were immunolabeled by
      the avidin-biotin complex method for two general markers (protein gene product
      9.5 and neuron specific enolase) and a range of normal and aberrant secretory
      products. RESULTS: In the early stages, characterised by vigorous pneumonitis,
      endocrine cells were normal in appearance and distribution but very few in
      number. They contained only those secretory products normally found in such cells
      in health; inappropriate substances were not seen. By the time of early fibrosis
      endocrine cells were even fewer. None were identifiable in the lungs affected by
      honeycombing, despite the fact that all contained intact, well preserved
      epithelium. CONCLUSIONS: It seems unlikely that the products of pulmonary
      endocrine cells can have any role in the pathogenesis of diffuse pulmonary
      fibrosis in man, the diminution in their number with advancing fibrosis probably
      reflecting their loss simply as a consequence of generalised epithelial damage.

PMID- 8303634
TI  - Tuberculin testing in residential homes for the elderly.
AB  - BACKGROUND: Evidence from the United States has shown that tuberculin sensitivity
      increases with length of stay among residents in homes for the elderly, implying
      an increasing risk of infection. There is no evidence as to whether or not
      residents in homes in the United Kingdom have a similar risk. METHODS: A study
      was undertaken to determine whether residence in a home for the elderly increases
      the risk of tuberculosis infection. Over a six month period all residents in
      homes for the elderly in Liverpool received a tuberculin test. A health
      questionnaire was completed by the field team for each resident. A total of 2665
      residents in homes for the elderly were surveyed. RESULTS: Heaf test grade
      positivity declined with age, the odds ratio being 0.71 for each 10 year period.
      Adjusting for age, there was no change in Heaf test grade with length of stay in
      the home. Heaf test positivity was stronger in smokers (odds ratio 1.59) than ex
      smokers (odds ratio 1.20) and non-smokers. Heaf test grade positivity was
      directly related to pack years. Allowing for age and smoking, the odds ratio for
      men compared with women for a positive test was 1.62 (95% confidence interval
      1.32 to 1.99). CONCLUSIONS: Heaf test positivity declines with age. Residence in
      a home for the elderly is not associated with increased rate of tuberculosis
      sensitivity. Smoking and male gender is associated with increased Heaf test
      positivity.

PMID- 8303635
TI  - Chlamydia pneumoniae seroprevalence in immunocompetent and immunocompromised
      populations in Milan.
AB  - BACKGROUND: Chlamydia pneumoniae is drawing increasing attention as an agent of
      respiratory tract infection. Specific antibody prevalence in western countries is
      low in preschool children and reaches more than 50% in adults. However, little is
      known about the prevalence of this infection in immunocompromised subjects such
      as HIV-I infected patients. The aim of this study was to evaluate the
      seroprevalence of Chl pneumoniae in immunocompetent and immunocompromised (HIV-1
      infected) paediatric and adult populations. METHODS: Between March 1991 and
      September 1992 764 healthy subjects (421 men and 343 women, age range six months
      81 years), 96 HIV-I infected (73 men and 23 women, age range 18-35 years) and 126
      HIV-I negative intravenous drug users (92 men and 34 women, age range 18-37
      years), and 50 children (23 boys and 27 girls, age range 8-123 months) with
      vertically transmitted HIV-I infection were studied. For each subject an HIV-I
      test (ELISA and Western blot) was performed, together with a
      microimmunofluorescence test for IgG and IgM antibodies to Chl pneumoniae
      specific antigen (TW-183). RESULTS: In the healthy population a low prevalence
      (11%) was observed in children under 10 years of age, which increased
      progressively to 58% in adults over 70 years. In the HIV-I infected population
      Chl pneumoniae seroprevalence was higher than in immunocompetent controls
      (children, 26% v 11%; drug users, 60% v 40%). Moreover, in drug users this
      difference was also observed in comparison with HIV-1 negative intravenous drug
      users (60% v 33%). CONCLUSIONS: Our data on Chl pneumoniae seroprevalence in a
      healthy population are consistent with those reported by others in western
      countries. Moreover, HIV-I infected subjects seem to be at higher risk of
      developing Chl pneumoniae infections.

PMID- 8303636
TI  - Pulmonary rehabilitation in chronic respiratory insufficiency. 5. Home mechanical
      ventilation.

PMID- 8303637
TI  - Respiratory gas exchange using a triaxial alveolar gas diagram.
AB  - A triaxial alveolar gas diagram to depict fractional concentration of oxygen,
      carbon dioxide and nitrogen is described, in which the R = 1 line is always
      implicit. Although it is not claimed that this representation leads to new
      insights into respiratory physiology, a method of plotting on a triaxial
      coordinate system has been found to be well suited to many applications when a
      direct display of fractional nitrogen concentration is required.

PMID- 8303638
TI  - Long term survival in non-encapsulated primary liposarcoma of the mediastinum.
AB  - An elderly woman presented with dyspnoea secondary to extensive mediastinal
      invasion by a primary well differentiated liposarcoma of the mediastinum. Five
      years after partial resection and postoperative radiotherapy (45 Gy) she is alive
      and well. To our knowledge, long term survival has not previously been reported
      for a non-encapsulated mediastinal liposarcoma treated by incomplete resection
      and subsequent radiation therapy.

PMID- 8303639
TI  - Gastropleural fistula following pulmonary resection.
AB  - A 77 year old man with an eight month history of polymyalgia rheumatica treated
      by steroids underwent left lower lobectomy for a non-small cell carcinoma.
      Following discharge he developed a pneumothorax, empyema, septicaemia, and acute
      renal failure. Reinvestigation and reoperation showed this to be caused by a non
      malignant non-traumatic direct gastropleural fistula.

PMID- 8303640
TI  - Use of continuous positive airway pressure in the management of community
      acquired pneumonia.
AB  - Three cases of severe community acquired pneumonia requiring ventilatory support
      are presented. Continuous positive airway pressure (CPAP) applied via a tightly
      fitting face mask was used and was successful in two cases; the third required
      intermittent positive pressure ventilation. More extensive use of CPAP in these
      circumstances should be considered.

PMID- 8303641
TI  - Endobronchial nocardial infection.
AB  - The rare presentation of nocardial infection as an endobronchial "tumour" is
      reported. Haematogenous dissemination occurred after fibreoptic bronchoscopy and
      biopsy, a phenomenon not previously described in nocardial infections. This case
      highlights the difficulties in diagnosing pulmonary nocardial infection and the
      potential for invasive procedures to disseminate the disease.

PMID- 8303642
TI  - Mycobacterial contamination of fibreoptic bronchoscopes.
AB  - Contamination of bronchoalveolar lavage specimens by environmental mycobacteria
      in hospital water supplies may lead to diagnostic confusion, particularly in
      immunocompromised patients. Mycobacteria may become concentrated in the tubing of
      bronchoscope disinfecting machines. It is very difficult to eradicate these
      organisms once contamination has occurred.

PMID- 8303643
TI  - Unilateral wheeze caused by pseudomembranous aspergillus tracheobronchitis in the
      immunocompromised patient.
AB  - Unilateral wheeze in the immunocompromised patient with unremitting fever may be
      the first localising sign of aspergillus tracheobronchitis. Two such cases are
      presented.

PMID- 8303644
TI  - Pulmonary nodules due to reactive systemic amyloidosis (AA) in Crohn's disease.
AB  - Multiple nodules of AA (reactive systemic) amyloid were identified at necropsy in
      the lungs of a patient with Crohn's disease. No other organs were involved.
      Nodular pulmonary amyloidosis is usually caused by deposition of AL (primary)
      amyloid.

PMID- 8303645
TI  - Accuracy of the typical computed tomographic appearances of fibrosing alveolitis.

PMID- 8303646
TI  - Diagnostic rigid and flexible oesophagoscopy in carcinoma of the oesophagus: a
      comparison.

PMID- 8303647
TI  - Respiratory symptoms questionnaire for asthma epidemiology: validity and
      reproducibility.

PMID- 8303648
TI  - beta 2-Glycoprotein I-dependent and-independent anticardiolipin antibody in
      patients with end-stage renal disease.
AB  - We investigated whether anticardiolipin antibody (aCL), which is common in
      patients with end-stage renal disease (ESRD), was dependent on beta 2
      glycoprotein I (GPI), a cofactor of aCL. Lupus anticoagulant (LA) was identified
      in 13/39 hemodialysis (HD) patients. GPI-independent aCL was positive in 12/39 of
      this group, five of whom had both GPI-independent aCL and LA. Three of the 20
      patients on symptomatic and supportive treatment other than HD had LA, but none
      of them were aCL positive. When GPI was added to the assay system to allow for
      GPI-dependent aCL measurement, the optical density (OD) readings of 10/12 HD
      patients decreased, thus proving that they were negative for aCL. In contrast,
      the OD readings of 6 control patients with systemic lupus erythematosus (SLE)
      increased markedly (3/6) or decreased slightly to moderately (3/6), however,
      within the limits of positive range, indicating GPI-dependent cCL positivity.
      These results suggested that LA and GPI-independent aCL were produced in ESRD
      patients, especially those on HD, possibly through mechanisms related to the
      hemodialysis membrane. However, the significance of GPI-independent aCL in this
      clinical setting, which may differ from the GPI-dependent aCL detected in SLE
      patients, as well as the possible participation of serum GPI in the production of
      aCL remain to be clarified.

PMID- 8303649
TI  - Red blood cell aggregation and primary hyperlipoproteinemia.
AB  - Erythrocyte aggregation (EA) was determined in a Myrenne aggregometer at stasis
      (EAMo) and low shear (EAM1) in 102 patients suffering from primary
      hyperlipoproteinemia (PHLP)-46 with familial hypercholesterolemia (FH); 28 with
      familial combined hyperlipemia (FCHL); 28 with primary hypertriglyceridemia
      (PHTG)-and in a control group (CG) of healthy matched subjects. EA was also
      determined in FH after the autologous plasma had been replaced by a control
      plasma. The following parameters were also measured: fibrinogen (Fbg), plasmatic
      lipids, apolipoproteins, glucose, HbA1 c and membrane erythrocyte lipids:
      cholesterol (C) and phospholipids (PL). An increase in both EAMo and EAM1 was
      observed in all the studied groups of patients. When erythrocytes of FH were
      resuspended in control plasma, EA normalized, but only in 75% of them. Fbg was
      elevated only in FH and FCHL. Membrane C was increased mainly in FH and FCHL. EA
      correlates with both Fbg and apolipoproteins. In FH, EA also correlates with
      membrane C/PL. In addition, a high significant correlation exists between EA and
      HbA1 c in FCHL. The results obtained suggest that not only Fbg and
      apolipoproteins but also possible changes in erythrocyte membrane could encourage
      EA in PHLP.

PMID- 8303650
TI  - Aggregation of human and canine platelets: modulation by purine nucleotides.
AB  - This study compared the responses of canine and human platelets to various
      aggregating agonists in the presence or absence of extracellular ATP and ATP
      analogues. Canine and human platelets were approximately equally reactive with
      ADP or collagen while the canine platelets were about 10 fold more sensitive to
      thrombin. Canine platelets were insensitive to the thromboxane mimetic U46619 but
      were synergistically aggregated by a mixture of ADP and U46619. Human platelets
      were very sensitive to U46619. Aggregations of human platelets with all of the
      above agonists were inhibited by extracellular ATP; beta, gamma methylene ATP
      (beta gamma ATP) and benzoyl ATP (BzATP) with a rank order suggestive of an
      interaction with P2x-like purinoceptors which support our previous findings. The
      comparable aggregations of canine platelets were likewise inhibited by ATP and
      its analogues but with a rank order suggestive of an interaction with P2y-like
      purinoceptors. ATP inhibited U46619- and ADP-induced aggregation of human
      platelets and ADP-induced aggregation of canine platelets, presumably, in part,
      due to competition for the ADP P2T receptor. However, when U46619 was added to
      either ATP or ATP analogue-inhibited ADP-treated canine platelets, the inhibition
      was nullified. Furthermore, we demonstrated, for the first time, that the canine
      thromboxane receptor becomes reactive to U46619 alone after incubation at room
      temperature for 3.5-5 hrs while human platelets become inactive under similar
      conditions. The implication of these studies is that there are significant
      differences in the canine and human platelet thromboxane and purine receptors.
      The future characterization of these differences and the mechanism by which they
      function should further our understanding of the impact of extracellular ATP on
      hemostasis and thrombosis.

PMID- 8303651
TI  - Evidence for sustained platelet activation in patients with early postinfarction
      angina.
AB  - Excretion of 2,3-dinor-thromboxane B2 released from activated platelets has been
      found elevated in patients with acute myocardial infarction and unstable angina.
      To investigate the role of thrombotic activity in postinfarction angina we
      measured urinary concentrations of 2,3-dinorthromboxane B2 in 20 patients over 10
      days after myocardial infarction. Compared with 11 patients recovering pain-free,
      excretion of 2,3-dinorthromboxane B2 was found elevated in 9 patients who
      developed postinfarction angina. Accordingly, early postinfarction angina appears
      to be associated with ongoing thrombotic activity.

PMID- 8303652
TI  - A primary platelet disorder of consanguineous simmental cattle.
AB  - A severe hereditary hemorrhagic diathesis in Simmental cattle has been identified
      in North America. Platelet numbers and coagulation profiles of affected cattle
      are normal. We have further characterized the severe dysfunction of platelet
      aggregation. All agonists tested elicited normal shape change. Aggregations in
      response to ADP, A23187, and collagen were absent. Aggregations were decreased or
      required more time for completion in response to PAF and thrombin. No
      ultrastructural abnormalities were observed in transmission electron micrographs.
      Dense granule release of ATP in response to PAF was normal. Thrombin-induced
      aggregation was dependent upon external calcium concentration in normal but not
      affected animals. Clot retraction in the blood from affected animals was
      abnormal. The data implicate a defect of Ca++ mobilization or utilization.

PMID- 8303653
TI  - Synthesis of tissue factor messenger RNA and procoagulant activity in breast
      cancer cells in response to serum stimulation.
AB  - The procoagulant activity observed in many types of tissue and cultured cells is
      due to tissue factor, a 30 kd transmembrane protein. The mRNA for tissue factor
      is a 2.2-kb species, which in some non-cancer cells can be up-regulated or
      induced by cytokines or by serum stimulation. In this study, induction of
      procoagulant activity in cancer cells was evaluated using the breast cancer cell
      line, MCF-7, and an adriamycin resistant subline, AdrRMCF-7, which has increased
      tumorigenicity in nude mice compared to the parental cell line. Procoagulant
      activity was factor VIIa dependent and was inhibited by an anti-tissue factor
      antibody. MCF-7 cells had minimal tissue factor activity, while AdrRMCF-7 cells
      had an 10-fold increase compared to the parental line. This increase was not
      observed in MCF-7 cells transfected with the multi-drug resistant gene, which is
      associated with adriamycin resistance. Serum stimulation of quiescent MCF-7 cells
      increased tissue factor activity 5-fold over baseline level, but did not increase
      activity in cells grown in serum-replete medium. Tissue factor activity of
      AdrRMCF-7 quiescent cells and AdrMCF-7 cells grown in serum-replete medium was
      enhanced 2-fold by serum stimulation. The predominant tissue factor mRNA species
      in MCF-7 cells was a 3.2 to 3.4-kb band, which increased in response to serum
      stimulation of cells grown in serum-replete medium. The mature 2.2-kb tissue
      factor mRNA band was detected in quiescent MCF-7 cells within six hours of serum
      stimulation and remained present 24 hours after stimulation. Synthesis of the 2.2
      kb tissue factor mRNA species in MCF-7 and AdrRMCF-7 cells correlated with
      appearance of procoagulant activity. Thus, while procoagulant activity correlates
      with the level of the 2.2-kb tissue factor mRNA species in these cancer cells,
      there are inherent differences in tissue factor activity, antigen, and mRNA
      levels, as well as in regulation of its synthesis between these cells.

PMID- 8303654
TI  - A memorial to Sol Sherry, M.D. (1916-1993).

PMID- 8303655
TI  - Phase I--study with aprosulate, a new synthetic anticoagulant.
AB  - This paper describes the first human study with aprosulate, a new chemically
      synthesized anticoagulant with a defined molecular structure and a molecular
      weight of 2388. Twelve healthy male volunteers received subcutaneous injections
      of placebo on the first day followed by ascending doses of aprosulate in the
      range of 0.25 mg/kg to 2.0 mg/kg body weight on alternate days. Anticoagulant,
      pharmacokinetic and safety parameters were assessed for 48 hours after each
      injection. The activated partial thromboplastin time and the Heptest showed a
      dose-dependent increase for up to ten hours after each application. A trend
      towards prolongation of the bleeding time was indicated with higher doses. In
      general, the tolerance was good. Plasma transaminase concentrations were raised
      in some volunteers but returned spontaneously to normal during or after the
      study.

PMID- 8303656
TI  - Aspirin fails to inhibit platelet aggregation in sheep.
AB  - This is the first report in which aspirin (ASA) has failed to inhibit aggregation
      of mammalian platelets. Preincubation of citrated sheep platelet rich plasma with
      a final concentration of 500 microM ASA for 3 minutes at 37 degrees C did not
      inhibit aggregation induced by either arachidonic acid (AA; 1.6 mM), ADP (2.5
      microM), collagen (5.6 micrograms/ml) or thrombin (0.04U). Instead, ASA
      potentiated the aggregation response produced by these agents except AA. Platelet
      aggregation that was reversible with ADP became irreversible after adding ASA.
      The inhibitory properties of ASA was confirmed with human platelets, challenged
      with AA, ADP, adrenalin and collagen. These findings suggest that sheep platelets
      have an ASA resistant cyclo oxygenase and may be able to aggregate by a pathway
      that is independent of arachidonic acid.

PMID- 8303657
TI  - Specificity of the sequence in Phe-Gln-Val-Val-Cys (-3-nitro-2-pyridinesulfenyl)
      Gly-NH2--a selective inhibitor of thrombin-induced platelet aggregation.
AB  - Thrombin-induced platelet aggregation is mediated in part by the intracellularly
      activated calpain expressed onto the external side of the membrane. We have
      previously shown that P1, Phe-Gln-Val-Val-Cys(Npys)-Gly-NH2 [Npys = 3-nitro-2
      pyridinesulfenyl], an affinity analog corresponding to the highly conserved
      sequence Gln-Val-Val-Ala-Gly-NH2, present in domains 2 and 3 of human kininogens,
      was an irreversible inhibitor of platelet calpain (second-order rate constant =
      5.85 mM-1 s-1). P1 also selectively blocked thrombin-induced platelet
      aggregation. We have now synthesized twenty-three other peptides, analogous to
      P1, and evaluated them to define the specificity of the amino acid sequence in P1
      to selectively block thrombin-induced platelet aggregation. We find that
      replacement by Leu of Val and by Tyr of Phe adjacent to Gln is minimally
      tolerated and the resulting peptides are partially effective in selectively
      blocking thrombin-induced platelet aggregation. The presence of valine adjacent
      to cysteine in P1 is essential for the inhibitor to selectively block thrombin
      induced platelet aggregation. The presence of valine adjacent to cysteine in P1
      is essential for the inhibitor to selectively block thrombin-induced platelet
      aggregation. Extensions of the N-terminal sequence in P1 did not improve its
      selectivity. Ac-Ala-Gln-Val-Val-Ala-Gly-NH2 (Ac, acetyl), a peptide containing
      the conserved sequence but lacking the Npys function, neither inhibited platelet
      calpain nor platelet aggregation induced by thrombin. Presence of the peptide
      sequence and Npys function are both required in P1 for its selective action in
      inhibiting platelet aggregation induced by thrombin.

PMID- 8303658
TI  - Antithrombin III producing hepatocellular carcinoma.
AB  - A case of primary hepatocellular carcinoma with an abnormal increase in the
      antigenic quantity and activity of Antithrombin III (AT-III) is reported. The
      patient was a 53-year-old man. The liver was palpated for a five fingerbreadths,
      but no jaundice or ascites was noted. Computed tomogram (CT) revealed the
      presence of many nodules of various sizes in the right hepatic lobe. Both viral
      markers of HBV and HCV were negative. For tumor markers, PIVKA-II was high (27.7
      AU/ml) but AFP was normal. Among coagulation and fibrinolytic factors, the
      activity and antigenic levels of AT-III were abnormally high (290% and 81.6
      mg/dl). An US guided needle biopsy of the tumor revealed hepatocellular
      carcinoma, Edmondson I. The cellularity was high and the tumor cells were small,
      well differentiated. The tumor cells were positively stained in
      immunohistochemical staining using the anti-AT-III antibody. It was believed that
      AT-III produced by the tumor cells was responsible for this exaggerated level.

PMID- 8303659
TI  - Coagulation in vivo microcirculation and in vitro caused by endothelin-1.
AB  - This study was designed to elucidate the participation of endothelin-1(ET-1) in
      vivo and in vitro coagulation. The microvascular hemodynamic changes in terms of
      intravascular thrombus formation in rat mesentery induced by the superfusion of
      ET-1 (0.5, 1 and 2 pmol) were visualized by an intravital microscope system
      assisted by television-video tape recorder system. In addition to
      vasoconstriction we observed the blockade of circulation by clumps resembling
      thrombus in a dose dependent fashion by ET-1. Thrombus formation could be
      attenuated by pretreatment with superfusion of 3.8% Na citrate solution but not
      by the prior superfusion of 1 to 3 ng of nitroglycerine. Thrombus formation was
      found after the administration of 10 microliters of CaCl2 (100 nM) solution in Na
      citrate (3.8%, 20 microliters) and ET-1 treated field. In vitro study, a dose
      dependent increase in TAT (thrombin-antithrombin complexes) and decrease in AT
      III (antithrombin III) (%) activity, the prolongation of PT (prothrombin time)
      and APTT (activated partial thromboplastin time) was found by administering ET-1
      immediately in native (unanticoagulated) blood in silicon coated test tubes (p <
      0.05; n = 6). However in citrated blood, TAT complexes, AT III (%) activity, PT
      and APTT were not significantly changed after administration of the same doses of
      ET-1 (p > 0.05; n = 6). Therefore, this study suggested that endothelin-1 caused
      intravascular thrombosis and enhanced intra test tube coagulation which could be
      attenuated by blocking ionic calcium.

PMID- 8303660
TI  - Impaired fibrinolysis in patients with Blackfoot disease.
AB  - Blackfoot disease is a unique endemic and chronic progressive arteriosclerotic
      vascular disease in southwest area of Taiwan. In this study, we determined the
      plasma levels of tissue plasminogen activator (tPA), plasminogen activator
      inhibitor (PAI), urokinase plasminogen activator (uPA), and von Willebrand factor
      (vWF) antigen in Blackfoot disease patients, in comparison with normal controls
      from non-endemic areas and the endemic area, Putai. Blackfoot disease patients
      had mean tPA antigen level of 7.9 ng/ml (n = 27) which was significantly lower (p
      < 0.05) than both the normal controls with 11.0 ng/ml (n = 20) and the Putai
      normal controls with 9.7 ng/ml (n = 39). However, the mean PAI-1 antigen level in
      the patient group was 41.2 ng/ml (n = 28) which was significantly higher (p =
      0.0001) than both the normal controls with 19.7 ng/ml (n = 23) and the Putai
      normal controls with 21.3 ng/ml (n = 40). Furthermore, in the patient group, a
      significantly lower (p < 0.005) mean uPA antigen level (2.3 ng/ml, n = 18) was
      noted as compared with that in the normal controls (3.2 ng/ml, n = 14). No
      significant difference was observed in vWF antigen level between patients and
      normal controls. This study suggests that a reduced capacity for fibrinolysis is
      associated with Blackfoot disease.

PMID- 8303661
TI  - Effects of dipyridamole, pentoxifylline or dipyridamole plus pentoxifylline on
      platelet reactivity in patients with ischemic cerebrovascular insufficiency.
AB  - Platelet activation and the subsequent platelet recruitment induced by activated
      platelets released products constitute the initial events of platelet thrombus
      formation. We have evaluated the recruiting activity of collagen-stimulated whole
      blood in patients with ischemic cerebrovascular insufficiency. This was done
      using an experimental approach that allows independent evaluation of platelet
      activation and recruitment. The effects of of treating the patients with
      dipyridamole (DIP) (300 mg/day), pentoxifylline (POX) (1200 mg/day) or a
      combination of the two drugs at the same doses was also evaluated before and
      after 7, 15, and 45 days of treatment. DIP decreased the recruiting activity in a
      time-dependent manner, while POX did not show any effect. However, the combined
      treatment with DIP+POX was more effective than DIP alone in reducing platelet
      recruitment, which was abolished after 45 days of treatment. Studies using the
      drugs in vitro indicated a greater inhibitory activity of the drug association
      than either drug individually. The effects of the drug association in vitro, even
      at high concentrations, was lower than those observed ex vivo after 45 days of
      treatment. This suggests that DIP+POX in vivo may have effects that condition a
      reduced platelet response.

PMID- 8303662
TI  - Improved potency and specificity of Arg-Gly-Asp (RGD) containing peptides as
      fibrinogen receptor blocking drugs.
AB  - A range of cyclic RGD based peptides have been developed to mimic the
      conformation of RGD within fibrinogen. These peptides, as well as echistatin
      (IC50 = 0.05 microM) and GRGDS (IC50 = 25 microM) fully inhibited adenosine
      diphosphate (ADP) (10 microM)-induced platelet aggregation of human gel-filtered
      platelets (GFP). RGDF was the most potent linear peptide in inhibiting ADP
      induced aggregation (IC50 = 8 microM) but cyclisation, using a 6,5 bicyclic
      coupling group to produce GR83895, led to an approximately 10-fold increase in
      potency (IC50 = 0.9 microM). In GFP, ADP-induced 125I-fibrinogen binding was
      inhibited (> 80%) by echistatin, GRGDS or GR83895 at concentrations (IC50 values
      0.05 microM, 25 microM and 1.4 microM respectively) similar to those needed to
      inhibit aggregation. All three compounds also completely inhibited ADP- and
      U46619-induced aggregation in both platelet rich plasma (PRP) and whole blood. In
      contrast to platelet aggregation, U-46619-induced 14C-5HT secretion in PRP was
      not inhibited by GR83895 or echistatin, indicating that agonist-induced signal
      transduction is not affected by either agent, a profile consistent with that
      predicted for a specific fibrinogen receptor blocking drug. To test specificity
      of action, echistatin, GR83895 and GRGDS were also examined for their ability to
      detach cultured human umbilical vein endothelial cells attached to plastic
      through a vitronectin receptor dependent process. GR83895 only caused detachment
      at concentrations 100-fold greater than those required to inhibit platelet
      aggregation, in contrast to GRGDS and echistatin which caused cell detachment at
      concentrations similar to those inhibiting aggregation. In summary, cyclisation
      of RGD-containing peptides has led to both improved potency and specificity of
      action. Such specificity of action may prove to be an important consideration for
      the successful development of a fibrinogen receptor blocking drug as an anti
      thrombotic drug.

PMID- 8303663
TI  - Preparation of oversulfated fucoidan fragments and evaluation of their
      antithrombotic activities.
AB  - Oversulfated fucoidan fragments (20-40 and 40-60 kDa) were prepared, and their
      fibrinolytic and anticoagulant activities were compared with those of
      oversulfated fucoidan (100-130 kDa) reported previously [Soeda et al., Biochem.
      Pharmacol. 43, 1853-1858, 1992]. The results of these experiments indicated that
      the in vitro abilities of oversulfated fucoidan to stimulate tissue plasminogen
      activator (t-PA)-catalyzed plasminogen activation and to potentiate thrombin
      inhibition by antithrombin III or heparin cofactor II decreased with a decrease
      in its molecular size. However, the preventive effects of both fucoidan fragments
      on endotoxin-induced hepatic vein thrombosis in hyperlipemic rats were almost the
      same as that of oversulfated fucoidan (100-130 kDa). We also found that, unlike
      heparin treatment, the concentrations of serum and vascular endothelium t-PA in
      rats treated with oversulfated fucoidan or its fragments (1 mg each/kg/week) were
      maintained at normal levels. The 20-40 and 40-60 kDa fragments had an ability to
      decrease the elevated levels of serum cholesterol in hyperlipemic rats, whereas
      the 100-130 kDa fucoidan derivative did not. These results suggest that
      oversulfated fucoidan and its fragments have another function(s), besides the
      regulation of blood coagulation and fibrinolysis, and are of therapeutic benefit
      for the prevention of thrombus formation in hyperlipemia.

PMID- 8303664
TI  - The effect of N-3 fatty acids and nifedipine on platelet function in hypertensive
      males.

PMID- 8303665
TI  - Mast cell lysate induces a procoagulant effect on endothelial cells.

PMID- 8303666
TI  - Compared activity of human, rat and rabbit plasma tissue factor pathway
      inhibitors.

PMID- 8303667
TI  - Immunoelectrophoresis and ELISA techniques for assay of plasma beta 2
      glycoprotein-1 and the influence of plasma lipids.
AB  - Beta 2 glycoprotein-1 (beta 2GP1) has been identified as a cofactor for the
      binding of some antiphospholipid antibodies to anionic phospholipids and has been
      demonstrated to possess anticoagulant properties in vitro. We have investigated
      Laurell rocket immunoelectrophoresis (IEP) and ELISA techniques for measurement
      of beta 2GP1. Western blotting and crossed immunoelectrophoresis (CIE) of plasma
      demonstrated free beta 2GP1 and beta 2GP1 complexed with unidentified plasma
      constituents. The free and complexed forms were not distinguished in
      immunoelectrophoresis assays, allowing measurement of total beta 2GP1. Standard
      and detergent modified IEP and ELISA techniques were compared: significant
      correlation was demonstrated between unmodified and detergent modified IEP,
      detergent modified IEP and ELISA and unmodified IEP and ELISA. The intra-assay co
      efficients of variation (CVs) of the unmodified and modified IEPs and ELISA were
      7.5, 3.7 and 7.9%. Inter-assay CVs determined for the modified IEP and ELISA were
      5.8 and 9.1% respectively. The purified beta 2GP1 used to standardise the assays
      was shown to have subfraction selectivity and different calibration values were
      obtained for pooled normal plasma by the unmodified IEP (242 mg/l) and modified
      IEP and ELISA (201 mg/l). We have also investigated the influence of some pre
      test variables on beta 2GP1 levels and shown that heparin, citrate or EDTA plasma
      and serum samples are suitable for assay of this glycoprotein and that levels are
      unaffected by repeated freeze/thawing. The influence of plasma lipids on beta
      2GP1 measurement was also examined and we demonstrated no significant differences
      between pre and postprandial samples, which suggests that fasting status is not
      an important consideration for assay of beta 2GP1 in healthy subjects.

PMID- 8303668
TI  - Choice of standard plasma for diagnosis and quantitation of lupus anticoagulants.
AB  - We have recently developed a computer-assisted, semi-automated test for lupus
      anticoagulants (LA), based on the Activated Partial Thromboplastin Time (APTT)
      and the Russell's Viper Venom Time (RVVT). In this test, plasma samples mixed 1:1
      with pooled normal plasma are tested at one low (screening procedure) and one
      high (confirming procedure) cephalin concentration, using an automated clot
      timer. The ratio of these two clotting times, divided by the corresponding ratio
      for normal plasma, was defined as the Lupus Ratio (LR). Based on the LR of
      several dilutions of a strong LA positive plasma, a standard curve was
      constructed for LA quantitation in both the APTT and the RVVT system. In the
      present article, we discuss the use of different LA positive plasma as standards
      for the identification as well as quantitation of LA. Due to the heterogeneity of
      LA, the shape and slope of the standard curves as well as the cut-off points
      between "normal" and "pathological" values varied from one plasma to another.
      Thus, the result of LA quantitation of a given plasma varied considerably,
      according to the choice of standard plasma. A strong LA plasma should be chosen
      as a standard, since any standard plasma only allows the quantitation of plasmas
      with a lower LR than its own. A pool of several plasmas is also suitable as a
      standard. In addition to LA quantitation, such a standard could be used to define
      the cut-off between "normal" and "abnormal" results in each assay, as a certain
      dilution of the standard plasma. The present study also confirms the greater
      sensitivity of the APTT as compared to the RVVT for LA detection.

PMID- 8303669
TI  - Elevated platelet microparticles in transient ischemic attacks, lacunar infarcts,
      and multiinfarct dementias.
AB  - Platelets release microparticles (PMP) upon activation. Elevated levels of PMP
      were observed in patients with immune thrombocytopenic purpura (ITP), sometimes
      associated with a syndrome resembling transient ischemic attack (TIA), suggesting
      a thrombogenic potential for PMP. To determine if this association applies to TIA
      and other cerebrovascular accidents (CVA) without ITP, we studied PMP profiles in
      71 patients with ischemic CVA: 28 with small vessel CVA (SCVA), either lacunar
      infarcts or TIA; 24 with large vessel CVA (LCVA); 19 with multiinfarct dementia
      (MID); 12 with Alzheimer's dementia (AD); and 31 healthy controls. The mean PMP
      values were: MID = 3.71 +/- 0.51; SCVA = 3.48 +/- 0.63; LCVA = 1.97 +/- 0.28; AD
      = 1.19 +/- 0.27; controls = 0.88 +/- 0.09, (all units x 10(7)/mL). PMP values in
      all groups except AD were significantly above normal (p < 0.01). However, the
      elevation in SCVA was more marked than in LCVA (p < 0.01). Administration of the
      calcium channel blocker, nifedipine, to 11 TIA patients reduced PMP
      significantly.

PMID- 8303670
TI  - Thrombin treated plasma employed as a standard for determination of soluble
      fibrin.
AB  - The Coa-set Fibrin Monomer test (CFM-test) is a quantitative method for
      determination of soluble fibrin in plasma. The fibrin standard of the CFM-test is
      produced by bathroxobin conversion of purified fibrinogen to fibrin. Plasma
      treated with minute amounts of thrombin may be considered as a more physiological
      way of preparing fibrin monomers. Therefore, we have employed such thrombin
      treated plasma (TTP) as an alternative fibrin standard for the CFM-test. The
      fibrin concentration of the TTP was determined indirectly by quantitation of
      released fibrinopeptide A. The TTP was stable during freezing, thawing and
      storage for 3 months at -70 degrees C. The standard curve obtained using TTP as a
      standard was linear in the range of 0-275 nmol/l fibrin in plasma, but the slope
      of the line was less steep than the original standard curve. This difference was
      probably due to the greater plasminogen activating effect of bathroxobin digested
      fibrinogen compared to soluble fibrin generated in plasma by thrombin, as
      observed in a previous study. Because of the less steep slope of the alternative
      standard curve, fibrin levels in plasma samples from 20 healthy volunteers and 25
      patients were found to be higher employing TTP as a standard. Preparation of a
      fibrin standard by incubation of plasma with minute amounts of thrombin will to
      some extent mimic the process of fibrin generation in vivo. Since we have found a
      satisfactory stability of such a standard during freezing, thawing and storage,
      we think the TTP standard might be useful for quantitation of soluble fibrin in
      plasma.

PMID- 8303671
TI  - Endothelial cells release casein kinase II--like activity capable of
      phosphorylating fibrinogen in response to thrombin.
AB  - Rat liver endothelial cells cultivated in the absence of serum and activated with
      thrombin released up to 10% of the total protein kinase activity into the cell
      medium using casein or fibrinogen as the phosphate acceptor protein. The activity
      was partly inhibited by heparin, indicating that it was of the casein kinase II
      type. The release of kinase started directly after the addition of thrombin (2
      NIH U/ml) to the media with two maxima; one after about 10 min and the second
      after around 30 min. The phosphorylating activity of media from cells incubated
      for longer times was less dependent on thrombin-induction which probably
      indicated the start of destruction of the cells. The results reported suggest
      that phosphorylation of fibrinogen could occur in the blood under acute phase
      conditions.

PMID- 8303672
TI  - Possible involvement of oxygen-derived free radicals in abnormal hemostasis
      induced by SART stress (repeated cold stress) in laboratory animals.
AB  - Abnormal hemostatic profiles indicating hemorrhagic tendency have been reported
      in rodents exposed to prolonged fluctuation in ambient temperature, known as SART
      (specific alternation of rhythm in temperature)-stressed animals. In this study,
      investigation was made of possible involvement of oxygen-derived free radicals in
      the development of stress-induced hemostatic alteration. SART-stressed rats and
      mice exhibited marked decrease in platelet count, fibrinogen level and factor
      VIII:C activity. Superoxide dismutase, when administered s.c. twice a day to mice
      for 7 days of stress exposure, inhibited the above alterations. Catalase given in
      the same manner, had essentially the same effect, though to a lesser extent.
      Allopurinol administered orally once daily during stress reduced stress-induced
      thrombocytopenia, but caused considerable increase in fibrinogen and factor
      VIII:C activity in stressed and unstressed mice. Lipid peroxide significantly
      increased in the heart but not in the plasma following stress exposure in rats
      and mice. Active oxygens would thus appear to be, at least partially, involved in
      the development of abnormal hemostasis induced by SART stress.

PMID- 8303673
TI  - Cathepsin G activates human factor V in vitro.

PMID- 8303674
TI  - Platelets and the permeability of fibrin network developed in human plasma.

PMID- 8303675
TI  - Thrombi formation parameters in mesenteric arterioles and venules in rats.

PMID- 8303676
TI  - Changes of von Willebrand factor and antithrombin III levels in acute stroke:
      difference between thrombotic and haemorrhagic stroke.

PMID- 8303677
TI  - Venous occlusion test for the release of heparan sulfate from endothelium.

PMID- 8303678
TI  - Plasma levels of tissue factor pathway inhibitor in thrombophilic patients.

PMID- 8303679
TI  - Platelet aggregation by a collagen-like synthetic peptide.

PMID- 8303680
TI  - Lack of effect of isradipine on in vitro platelet activation.

PMID- 8303681
TI  - Shear dependence of the fibrin coagulation kinetics in vitro.
AB  - Fibrin thrombus formation, in vivo and in vitro, preferentially occurs in regions
      of retarded, recirculating flow which promote local variations of the
      distribution of blood components, e.g. thrombin, and shear rates. To better
      understand the effects of shear forces on the thrombin induced fibrin coagulation
      process the time course of fibrin formation in a fibrinogen/thrombin solution was
      studied for different shear rates gamma (0 s-1 < or = gamma < or = 500 s-1) and
      thrombin concentrations cthr (0.1 units/ml < or = cthr < or = 1.0 units/ml). The
      clotting curves at zero shear and the shear induced alterations of these curves
      could essentially be described in terms of a reaction kinetics defined by two
      rate coefficients k1, k2 which can be attributed to fibrinogen cleavage by
      thrombin and fibrin polymerisation, respectively. For cthr > approximately 0.5
      units/ml and gamma > approximately 15 s-1 an additional mechanism, presumably
      fibrin breakage, had to be assumed. The rate coefficient k2 was markedly more
      affected by cthr and shear forces then was k1. The results fit well to the growth
      kinetics of fibrin thrombi formed in glass models of an arterial branching.

PMID- 8303682
TI  - Tetrafibricin: a nonpeptidic fibrinogen receptor inhibitor from Streptomyces
      neyagawaensis (I). Its GPIIb/IIIa blockage on solid phase binding assay.
AB  - Tetrafibricin is a novel nonpeptidic fibrinogen receptor inhibitor isolated from
      Streptomyces neyagawaensis NR0577. Its competitive and selective fibrinogen
      receptor blockage was demonstrated in this study. Tetrafibricin competitively
      inhibited (Ki = 9.9 nM) the binding of biotinylated fibrinogen to purified active
      glycoprotein (GP) IIb/IIIa immobilized on plastic plate. When RGDS and
      tetrafibricin were added in combination, the inhibition was additive. The binding
      of other RGD-containing proteins, fibronectin and von Willebrand factor, to
      active GPIIb/IIIa were also completely inhibited by tetrafibricin. The fact that
      tetrafibricin did not inhibit the binding of von Willebrand factor to GPIb/IX
      indicates the specific blockage of tetrafibricin for GPIIb/IIIa. Fibrinogen
      receptor inhibition of tetrafibricin was also confirmed by its ability to inhibit
      125I-fibrinogen binding to platelets stimulated with ADP. Because of its
      competitiveness and specificity, tetrafibricin can be used in a new structural
      model for the design of fibrinogen receptor inhibitors.

PMID- 8303683
TI  - Tetrafibricin: a nonpeptidic fibrinogen receptor inhibitor from Streptomyces
      neyagawaensis. (II). Its antiplatelet activities.
AB  - Tetrafibricin; a nonpeptidic fibrinogen inhibitor from microbial origin, showed
      potent antiaggregation activities on human platelet aggregation induced by either
      ADP, thrombin or collagen (IC50s = 5.6, 7.6 and 11 microM, respectively) in
      platelet rich plasma. The ability to inhibit aggregation in platelets treated
      with chymotrypsin confirmed the GPIIb/IIIa blockage of tetrafibricin.
      Tetrafibricin blocked the release of serotonin induced by ADP but it did not
      block the release reaction induced by thrombin. When added to platelets formerly
      aggregated with ADP, tetrafibricin caused rapid and complete deaggregation. As
      for the selectivity among other Arg-Gly-Asp -dependent integrins, tetrafibricin
      seems to be more specific for glycoprotein (GP) IIb/IIIa than RGDS is. This is
      because it had no effect on adhesion of bovine aortic endothelial cells to RGD
      containing proteins. Tetrafibricin is the first nonpeptidic fibrinogen receptor
      inhibitor that may be valuable for the study on platelet aggregation inhibitors.

PMID- 8303684
TI  - Attenuation of thrombolysis by release of plasminogen activator inhibitor type-1
      from platelets.
AB  - Although platelets contain approximately 90% of the total amount of plasminogen
      activator inhibitor type-1 (PAI-1) present in blood, the functional significance
      of PAI-1 in platelets has been controversial. Most assessments of platelet PAI-1
      have been performed with platelet lysates in which the PAI-1 derived from
      platelets may have been inactivated during the course of lysis. This study was
      performed to determine whether elaboration of PAI-1 from platelets activated
      physiologically by thrombolysis of pre-formed clots inhibits activation of
      plasminogen by tissue-type plasminogen activator (t-PA). Human whole blood clots
      were formed in Chandler tubes, and release of PAI-1 from platelets was quantified
      during and after clot formation. Subsequently, clots were placed in different
      Chandler tubes, and the effects of platelet PAI-1 on lysis induced by t-PA were
      characterized. Both the activity and concentrations of PAI-1 elaborated from
      platelets peaked approximately 15 min after induction of clotting. Induction of
      clot lysis with t-PA, 1,000 to 5,000 ng/ml, was inhibited by platelet-rich
      compared with platelet-poor plasma. Platelets inhibited lysis of preformed clots
      by t-PA and plasminogen in buffer solutions as well. Both the inhibition of clot
      lysis and accumulation of PAI-1 released from platelets were prevented by
      attenuation of thrombin-mediated activation of platelets with hirudin.
      Furthermore, the PAI-1 mediated inhibition was obviated by blockade of PAI-1
      activity with a neutralizing monoclonal antibody to PAI-1. These results indicate
      that platelets inhibit clot lysis induced by t-PA by releasing functionally
      active PAI-1.

PMID- 8303685
TI  - Purification of anticardiolipin and lupus anticoagulant activities by using
      cardiolipin immobilized on agarose beads.
AB  - We describe a novel method for the purification of aPL, in which pure CL is
      immobilized on octyl-sepharose beads by hydrophobic interaction. No lipid
      contamination was present in eluates, and the system could be reutilized three
      times without loosing extracting capacity. Four patients with antiphospholipid
      syndrome were studied. A marked decrease in aCL and LA activities was found in
      all patient plasmas after the passage through a CL-octyl-sepharose column. Both
      activities were recovered in eluates which contained beta 2-GP-I and IgGs. beta 2
      GP-I was also present in normal plasma eluates, which showed no aCL and slight LA
      activity. This method represents an improvement in the purification of aPL, and
      could be useful in explaining the mechanism of action of antibodies that are
      obtained using pure phospholipid as extracting matrix.

PMID- 8303686
TI  - The impact of static work on fibrinolysis and platelet function.
AB  - Brief stress such as dynamic work protects against thrombosis by enhancing blood
      fluidity. The effect of isometric work on blood fluidity, however, is not known.
      The aim of the present study therefore was to test the effect of isometric work
      on heart rate (HR), blood pressure (BP), platelet function and fibrinolytic
      activity. Twelve healthy male volunteers were tested before and after isometric
      work. Isometric work resulted in an increase in HR from 62.4 to 110.0 beats/min
      and in systolic BP from 118.3 to 134.5 mmHg (p < 0.01). No significant change
      occurred in platelet release estimated as plasma levels of B-TG and PF-4, or
      platelet aggregation induced by ADP. Fibrinolytic activity increased, as
      evidenced by a decrease in ECLT from 136.7 + 10.5 to 72.3 + 9.8 min) (p < 0.01)
      and an increase in t-PA of 400%. No significant change was observed in PAI. The
      present data suggest that isometric work increases fibrinolytic activity
      significantly, but leaves platelet function unchanged.

PMID- 8303687
TI  - Platelets in essential hypertension.
AB  - The ultrastructure and adenosine diphosphate induced aggregatory response of
      platelets of 39 patients with essential hypertension have been studied. Both,
      transmission and scanning electron microscopy showed the co-existence of various
      morphological forms of platelets suggestive of activation. The hypertensive
      platelets also exhibited increased sensitivity to ADP induced aggregation
      confirming the activated state of platelets; the degree of activation correlated
      well with the levels of diastolic blood pressure.

PMID- 8303688
TI  - Plasma thrombomodulin levels are dependent on renal function.

PMID- 8303689
TI  - Euglobulin clot lysis induced by tissue type plasminogen activator in subjects
      with increased levels and different isoforms of lipoprotein (a).

PMID- 8303690
TI  - Tissue factor pathway inhibitor (TFPI) and its response to heparin in patients
      with spontaneous deep vein thrombosis.

PMID- 8303691
TI  - Detection of anticardiolipin antibodies in heat-inactivated normal human sera is
      not influenced by beta 2-glycoprotein-I.

PMID- 8303692
TI  - Warm heart surgery: a step backwards.

PMID- 8303693
TI  - Coronary artery resistance and oxygen uptake during reperfusion: is there any
      difference between warm and cold cardioplegia?
AB  - To evaluate the effects of warm continuous versus cold intermittent blood
      cardioplegia on coronary blood flow patterns after prolonged cardioplegic arrest,
      nine pigs underwent cardiopulmonary bypass with 210 minutes of aortic cross
      clamping. Antegrade blood cardioplegia was administered either cold intermittent
      (n = 4) or warm continuous (n = 5). During the first 30 minutes of reperfusion,
      there was decreased coronary blood flow with higher coronary vascular resistance
      in the cold group (mean +/- standard error; warm vs. cold: 30 min: flow: left
      anterior descending artery (LAD): 66 +/- 6 vs 36 +/- 4 ml/min, right coronary
      artery (RCA): 88 +/- 2 vs 61 +/- 4, p < 0.05, resistance: LAD: 33 +/- 3 vs 69 +/-
      5 dyn.s.cm-5 x 10(3), RCA: 41 +/- 3 vs 58 +/- 8, p < 0.05). After one hour of
      reperfusion there were no differences between groups. Arterio-venous oxygen
      difference was higher in the cold group after 15 min (3.1 +/- 0.5 vs 4.8 +/- 0.3
      ml O2/100 ml, p < 0.05) and 30 min (4.2 +/- 0.5 vs 6.2 +/- 0.7, p < 0.05) with
      equal values after 1 hour. During reperfusion there is reduced myocardial blood
      flow after cold intermittent blood cardioplegia. This may reflect superior
      myocardial protection with warm continuous cardioplegia.

PMID- 8303694
TI  - Protection of the ischemic immature heart--effect of perfusate reinfusion and
      composition.
AB  - We determined the influence of perfusate composition and reinfusion during
      ischemia upon myocardial protection in the immature rabbit heart. Isolated
      "working" hearts (n = 6 per group) from 7-10-day-old New Zealand White rabbits
      were perfused with Krebs bicarbonate buffer and function measured. Hearts were
      then arrested with 3 minutes cold (14 degrees C) perfusion with bicarbonate
      buffer (as hypothermia-alone group) or St. Thomas' II cardioplegic solution (as
      hypothermia-plus-cardioplegia group). Hearts were then subjected to hypothermic
      (14 degrees C) global ischemia for 2 or 6 hours, with and without multiple
      reinfusion of the coronary vasculature. Following 2 hours ischemia impaired
      recovery of aortic flow occurred after multiple reinfusion in comparison with a
      single infusion with the cardioplegic solution (64 +/- 3% versus 72 +/- 4%) but
      not with bicarbonate buffer (79 +/- 3% versus 83 +/- 4%). However after 6 hours
      ischemia impaired recovery of function occurred after multiple reinfusion in
      comparison with single infusion both with the cardioplegic solution (60 +/- 3%
      versus 68 +/- 3%) and with bicarbonate buffer (57 +/- 4% versus 75 +/- 5%). There
      were no differences in post-ischemic creatine kinase leakage or myocardial water
      content between groups. These results suggest (i) that reinfusion itself,
      regardless of the composition of the perfusate, caused decreased recovery of
      function after an extended period of ischemia, and (ii) protection of the
      ischemic immature heart with St. Thomas' II solution remains inadequate and
      requires improvement.

PMID- 8303695
TI  - Warm blood cardioplegia for patients undergoing revascularization for left main
      coronary artery disease.
AB  - Between February 1991 and June 1992, 62 patients (50 males) underwent coronary
      artery bypass (CAB) operation for significant left main coronary artery disease.
      Age varied between 47 and 81 years. 53 patients had unstable angina, 16 had
      recent myocardial infarction, and 16 had heart failure. 22 patients were in
      functional capacity class IV (Canadian Heart Association) and 2 patients were in
      unstable hemodynamical condition before the operation. Intraaortic balloon pump
      was inserted before the operation in 3 patients. Six patients had previous CAB
      surgery. All the patients were operated using myocardial protection with warm
      blood cardioplegia, given antegradely and retrogradely in 58 and only antegradely
      in 4 patients. Body temperature was maintained at 30 +/- 1.8 degrees C. Number of
      distal anastomoses averaged 4.3 +/- 0.9. One patient underwent additional
      resection of a left atrial myxoma and another aortic valve replacement. LIMA
      (left internal mammary artery) was used to bypass the LAD in 58 (94%) patients.
      Early mortality was 3 cases (4.8%). Major and minor postoperative complications
      occurred in 17 patients. These data suggest that warm blood cardioplegia provides
      superior myocardial protection in patients with left main coronary artery
      disease.

PMID- 8303696
TI  - Is continuous normothermic blood cardioplegia really a practical way of
      myocardial preservation? Comparison with intermittent cold crystalloid
      cardioplegia.
AB  - Commencing in September 1991, 30 consecutive patients who underwent coronary
      artery bypass grafting were operated on employing continuous normothermic blood
      cardioplegia (Group 1). 2.83 +/- 0.81 distal anastomoses per patient were
      performed. The next 30 consecutive patients were operated on employing
      intermittent cold crystalloid cardioplegia (Group 2). 2.72 +/- 0.95 distal
      anastomoses per patient were performed in this group. Cross clamping and
      cardiopulmonary bypass times were similar in both groups. Electromechanical
      activity beginning time (69.00 +/- 94.04 sec. versus 101.50 +/- 78.26 sec., p <
      0.001) and QRS recovery time (10.92 +/- 8.35 min. verus 19.60 +/- 33.65 min., p <
      0.05) were significantly shorter in Group 1 than in Group 2. Maximal potassium
      levels during cardiopulmonary bypass and in the postoperative period did not
      significantly differ between the groups. Postoperative serum CPK-MB values were
      similar. Three patients in Group 1 and four in Group 2 needed IABP support in the
      early postoperative period. In Group 1, one and in Group 2 three patients
      suffered perioperative myocardial infarction (difference not significant).
      Postoperative cardiac index augmentation was significantly higher in Group 1 than
      in Group 2 (from 2.40 +/- 0.57 L/min/m2 to 3.04 +/- 0.60 L/min/m2 in Gr I, from
      2.39 +/- 0.64 L/min/m2 to 2.86 +/- 0.49 L/min/m2 in Gr II, p < 0.01). Coronary
      sinus oxygen saturations during aortic cross-clamping were significantly higher
      in Group 1 (53.32 +/- 12.18% versus 17.82 +/- 2.75%, p < 0.001). There were no
      rhythm disturbances in Group 1 (0%) but atrial fibrillation occurred in 5
      (16.66%) cases of the hypothermic group in the postoperative period. In Group 1,
      two patients, and in Group 2, three patients (difference is not significant) were
      lost in the early postoperative period. We can say that continuous normothermic
      blood cardioplegia is a safe alternative way of myocardial protection with good
      clinical results despite its discomfortable and complicated delivery technique.

PMID- 8303697
TI  - Short-term biventricular circulatory support in the regionally stunned pig
      myocardium.
AB  - Mechanical circulatory support is only meaningful when reversible myocardial
      damage exists. Prompt biventricular assistance during reperfusion for six hours
      was tried in the regionally sublethally injured pig myocardium which has
      perspective for recovery. Postmortem tissue was examined with a quickly performed
      histochemical technique for tissue viability. Animals underwent five coronary
      occlusions (5 min occlusion/10 min reperfusion). Postischemic systolic wall
      thickening, observed by direct echocardiography, fell about 50% (p < 0.05 vs base
      line) before treatment which paralleled cardiac inosine and lactate efflux.
      Biventricular unloading (n = 5) resulted in contractile recovery to 94 +/- 19% (p
      < 0.05 vs stunning), untreated pigs remained depressed (33 +/- 12%, n = 5).
      During circulatory support the arterial lactate levels rose three-fold,
      concomitant with a drop in pH of 0.2 units (p < 0.05). Post-mortem histochemistry
      showed scattered areas with decreased activities of cytoplasmic lactate
      dehydrogenase and mitochondrial beta-hydroxybutyrate dehydrogenase, irrespective
      of treatment. Transmission electron microscopy revealed irreversible damage to
      mitochondria in depleted areas in contrast to areas where enzyme activity was
      present. We conclude that prompt volume unloading during reperfusion accelerated
      contractile recovery of sublethally postischemic myocardium.

PMID- 8303698
TI  - Antidiuretic hormone and cardiovascular responses during and after coronary
      artery bypass surgery.
AB  - In order to evaluate correlations in changes of postoperative plasma antidiuretic
      hormone (ADH) concentrations and hemodynamic parameters, 23 patients undergoing
      coronary artery bypass surgery were observed. 6 patients required intraaortic
      balloon pumping (IABP) (group I), 8 patients did not require IABP or inotropic
      agent (group II), and 9 patients required inotropic agent (group III) for weaning
      from cardiopulmonary bypass (CPB). Soon after CPB mean arterial and pulse
      pressures were significantly less in group I compared to other groups. Plasma ADH
      concentrations were significantly higher in group I than in group II, and showed
      significant negative correlation with hemodynamic parameters. On the 2nd
      postoperative day, plasma ADH concentrations in group I were significantly higher
      than in the other two groups, but were not correlated with hemodynamic
      parameters. Thus, early after surgery high plasma ADH concentrations in the IABP
      group directly reflected hemodynamic derangement, while at later times ADH
      secretion was influenced mainly by postsurgical stress.

PMID- 8303699
TI  - Time relationships in the diagnosis and treatment of left-atrial myxoma.
AB  - The records of 40 patients, 28 females and 12 males with a median age of 49 years
      (range 13-80 years), undergoing excision of left-atrial myxoma at 3 London
      hospitals during a 21-year period were reviewed. The urgency of treatment is
      discussed, and the interval between the onset of symptoms and diagnosis (median
      38 weeks), and also between diagnosis and surgery (< 48 hours) is considered.

PMID- 8303700
TI  - Preparation of in-vivo rat lung model for ischemia-reperfusion injury.
AB  - An in-vivo rat lung model for ischemia-reperfusion injury was prepared. The left
      lung was collapsed after hilar stripping, and the left main pulmonary artery and
      bronchus were clamped. After the determined period of clamping the left main
      pulmonary artery and bronchus were declamped and the right main pulmonary artery
      was clamped. Arterial gas analyses were performed, 1, 10, and 20 minutes after
      reperfusion. The wet/dry lung eight ratio was calculated and lungs were
      histologically examined. Before clamping, PaO2 was 102-155 mmHg in all animals.
      The experimental animals were divided into 4 groups; Group I: temperature 19
      degrees C, humidity 55% and duration of clamping 120 minutes (n = 2); Group II:
      23 degrees C, 55% and 120 minutes (n = 4); Group III: 23 degrees C, 55% and 90
      minutes (n = 5); Group IV: 23 degrees C, 65% and 75 minutes (n = 9). In Group IV,
      PaO2 decreased significantly in all 9 animals immediately after reperfusion, and
      at 1, 10, and 20 minutes it was 53.2 +/- 6.1 mmHg, 53.4 +/- 10.2 mmHg, and 67.0
      +/- 10.2 mmHg, respectively. Pulmonary edema was observed histologically in 7 of
      the 9 animals. In-vivo rat lung models for ischemia-reperfusion injury are
      affected by the surrounding conditions. We established a stable model by setting
      ischemic time, temperature, and humidity at 75 minutes, 23 degrees C, and 65%,
      respectively.

PMID- 8303701
TI  - Tumor presence at resection boundaries and lymph-node metastasis in bronchial
      carcinoma patients.
AB  - A prospective study was performed analyzing the bronchial resection boundaries of
      120 patients operated on for lung carcinoma. The resection boundary, maximum
      tumor diameter, distance between tumor and resection boundary, and lymph-node
      stage were analyzed by serial sections of the surgical specimens (lobes and
      lungs). The following results were obtained: 20/120 cases (17%) displayed
      microscopic tumor invasion of the resection boundary (R1 status), most frequently
      adenocarcinoma (21%). The R1 status was closely associated with the distance
      between tumor and resection boundary and postsurgical lymph-node state (pN
      stage): all 8 tumors excised at distance 1 mm or less from the bronchial
      resection boundary revealed bronchial submucous tumor growth, whereas none of the
      tumors located more than 20 mm from the resection boundary was found to display
      tumor invasion of the bronchial boundary. Curative resection was noted in all 40
      tumors operated at pNO stage and in only 11 cases (69%) of tumors with distant
      lymph-node metastases (pN3 stage). No relationship between tumor infiltration of
      the resection boundary and type of resection was seen. The data indicate that a)
      intra-operative control of bronchial resection boundaries is necessary in all
      lung-carcinoma patients with central tumor localization less than 20 mm from the
      proposed resection boundary; b) a "safety distance" between resection boundary
      and tumor boundary is of specific importance in bronchial carcinoma with lymph
      node metastases.

PMID- 8303702
TI  - Carcinosarcomas of the lung. Three case reports and literature review.
AB  - Therapy and course of pulmonary manifestations of carcinosarcomas in three
      patients are described. For this rare mixed tumor there is a prevalence among men
      between the ages of forty and seventy. Operative therapy should be employed
      whenever possible, because of the poor results achieved thus far using
      radiotherapy or chemotherapy. Carcinosarcomas were thought to have a worse
      prognosis than other non-small-cell bronchial carcinomas but an increasing number
      of reports indicate a similar clinical course and prognosis. Pneumonectomy was
      required for two of our patients and lobectomy was performed in the third. The
      period of observation extended over two years. One patient, tumor stage T4N0M0
      died of his disease after seven months. The two other patients, tumor stages
      T3N0M0 and T2N1M0, were operated on thirty-three and thirty-five months ago
      respectively and are clinically disease-free and in good health.

PMID- 8303703
TI  - Angiosarcoma of the chest wall with a gastric metastasis.
AB  - A rare case of chest-wall angiosarcoma with high tendency of local recurrence and
      with a solitary gastric metastasis is reported. The patient was an 84-year-old
      man who had a left lateral thoracic mass with a colic pain. The histological
      diagnosis of a biopsied specimen suggested an angiosarcoma. The first resection
      was performed, the resected specimen consisted of the 8th, 9th and 10th ribs
      including the tumor. However the tumor recurred around the primary site and the
      second resection was undertaken eight months after the first resection. Only
      three months after the second resection a second chest-wall recurrence together
      with a solitary gastric metastasis was found. Progressive emaciation, anemia and
      thrombocytopenia became evident, and the patient died the 40th day after the
      gastrectomy. Primarily a wide resection of the chest wall beyond the
      pathologically negative region around the tumor is thought to be necessary.

PMID- 8303704
TI  - Polyostotic coexisting fibrous dysplasia and aneurysmal bone cyst of the chest
      wall.
AB  - A case of a 39-year-old woman with a palpable mass in the right hemithorax is
      presented. The mass had been growing during the last 16 years. Radiographs and
      computed tomography showed two lesions in the right thoracic wall: the greater
      was in the anterior and lateral portion of the 7th rib, the minor lesion in the
      6th rib costovertebral joint. Both lesions were surgically removed. Histological
      examination demonstrated the association of fibrous dysplasia and aneurysmal bone
      cyst in the two lesions. The coexistence of these two lesions supports the theory
      that aneurysmal bone cyst may represent a secondary change due to haemodynamic
      alterations of the vascular bed caused by fibrous dysplasia.

PMID- 8303705
TI  - Highly acute course of ruptured papillary muscle of the tricuspid valve in a case
      of blunt chest trauma.
AB  - The sudden onset of tricuspid insufficiency following a blunt chest trauma is
      extremely rare. We operated on a young woman in a state of severe shock following
      a riding accident, in whom complete severing of the papillary muscle of the
      posterior tricuspid leaflet had occurred. The valvuloplasty operation itself and
      the postoperative course ran smoothly, apart from a late pericardial tamponade
      which required surgical revision. In accordance with other reported cases we
      believe that traumatic tricuspid insufficiency is still a very underestimated
      pathological occurrence. Echocardiographic examination should therefore be
      regarded as an essential standard procedure in all cases of blunt chest injury.

PMID- 8303706
TI  - Effect of vitamin B12 on performance and tissue selenium content in rats fed sub
      toxic levels of selenite.
AB  - The effects of vitamin B12 status on growth and tissue selenium distribution were
      studied in Sprague-Dawley rats chronically exposed to subtoxic levels of
      selenite. Vitamin B12 status was monitored by urinary methylmalonic acid
      excretion and by liver and plasma vitamin B12 levels. Selenite absorption was
      unaffected by dietary level of vitamin B12. A significant (P < 0.05) interaction
      of vitamin B12 and selenium was found on growth of rats fed vitamin B12 deficient
      or control diets. In vitamin B12 depleted rats, there were significant histologic
      changes in the liver that were characterized by micronodules and regeneration,
      bile duct reduplication, mild cirrhosis, necrosis of individual hepatocytes and
      other minor histologic changes. There was no gross or histologic evidence of
      liver toxicity in rats supplemented with vitamin B12. Rats pair-fed 9 mg/kg
      selenium with vitamin B12 had significantly lower liver and kidney selenium
      levels and significantly higher blood selenium levels compared to rats fed the
      diet without vitamin B12. These results are consistent with the hypothesis that
      vitamin B12 deficiency limits selenium methylation and excretion, resulting in
      higher tissue selenium levels and subsequent toxicity.

PMID- 8303707
TI  - Lack of alachlor induced DNA damage as assayed in rodent liver by the alkaline
      elution test.
AB  - Alachlor was studied in vivo for its capability to induce DNA damage, as
      evaluated by the alkaline elution test. The experiments were performed in mouse
      and rat liver after acute or subacute intraperitoneal or per os administrations
      of the chemical at sublethal dosages. Rat liver was also studied for DNA damage
      after administration of 2,6-diethylaniline, one of alachlor's major metabolites.
      Eluted DNA from treated animals was indistinguishable from control DNA. The
      results show that neither alachlor nor its metabolite cause DNA damage as
      determined by the number of single strand breaks.

PMID- 8303708
TI  - Immunosuppressive effects of highly chlorinated biphenyls and diphenyl ethers on
      T-cell dependent and independent antigens in mice.
AB  - The dose-dependent effects of 2,2',3,3',4,4',5,5',6-nonachlorobiphenyl (nonaCB),
      2,2',3,3',4,4',5,6,6'-nonaCB, 2,2',3,3',4,5,5',6,6'-nonaCB and decaCB on the
      suppression of the splenic plaque-forming cell (PFC) response to the T-cell
      dependent antigen, sheep red blood cells (SRBCs) and the T-cell-independent
      antigen, trinitrophenyl-lipopolysaccharide (TNP-LPS), were determined in
      genetically inbred mice. In addition, the induction of hepatic microsomal
      ethoxyresorufin O-deethylase (EROD) activity was also measured. The highly
      chlorinated biphenyls suppressed the splenic PFC response to SRBCs in C57BL/6 and
      DBA/2 mice and were relatively more active in the former strain. The C57BL/6 mice
      are more responsive to aryl hydrocarbon (Ah) receptor agonists than DBA/2 mice
      and these data support a possible role for the Ah receptor in mediating this
      response. However, previous studies with polychlorinated biphenyls (PCBs)
      indicate that congeners with 3 or 4 ortho-chloro substituents are inactive as Ah
      receptor agonists and this was consistent with the minimal induction of hepatic
      microsomal EROD activity by the highly chlorinated biphenyls in both strains of
      mice. Thus, the results suggest that the inhibition of the splenic PFC response
      to SRBCs observed in this study was primarily an Ah receptor-independent
      response. Some of the highly chlorinated diphyenyl ethers namely
      decachlorodiphenyl ether and 2,2',3,3',4,4',5,6,6'-nonachlorodiphenyl ether,
      inhibited the antigenic response to TNP-LPS in C57 BL/6 mice. The results
      indicate that the suppression of the TNP-LPS-mediated immune response may be a
      more reliable indicator of the Ah receptor-dependent immunotoxicity of
      halogenated hydrocarbons.

PMID- 8303709
TI  - Angiotensin I converting enzyme activity in adriamycin induced nephrosis in rats.
AB  - Activity of the dipeptidyl hydrolase angiotensin converting enzyme (ACE) has been
      observed to be altered by treatment with adriamycin (ADR). We used an animal
      model of ADR nephrotoxicity to study the effects on ACE in serum, urine and
      tissues on days 5, 10, 15, 20, 25 and 30 after ADR administration. Both
      glomerular and tubular injury occurred as evidenced by heavy proteinuria,
      albuminuria and increased urine N-acetyl glucosaminidase (NAG) excretion. Serum
      ACE was significantly elevated on days 20, 25 and 30. Of great interest was the
      excretion of ACE in urine of treated rats which ran parallel with the total
      protein excretion above the barely detectable levels found in controls. ACE
      activity increased in kidney, adrenal gland and liver on days 15, 20, 25 and 30.
      Heart and brain ACE levels increased on days 25 and 30. Increased ACE activity in
      aorta and lungs occurred on days 20, 25 and 30. ACE activity decreased in kidney,
      aorta, heart and brain on days 5 and 10. These observations strongly suggest a
      contribution of various tissues to elevate the serum ACE level. Urinary ACE may
      be of potential use as an index for renal glomerular and tubular damage.

PMID- 8303710
TI  - Teratogenic effects of various di-n-butyltins with different anions and butyl(3
      hydroxybutyl)tin dilaurate in rats.
AB  - In our previous study, di-n-butyltin diacetate has been shown to cause
      malformations such as cleft mandible, ankyloglossia, fused ribs, etc. in rat
      fetuses after oral treatment of maternal rats on day 8 of gestation. In this
      study, teratogenic effects of five di-n-butyltin compounds with different anions
      and also butyl(3-hydroxybutyl)tin dilaurate (3-OHDBTL) were examined in Wistar
      rats. Anion groups of these compounds were as follows: diacetate (DBTA),
      dichloride (DBTC), maleate (DBTM), oxide (DBTO) and dilaurate (DBTL). On day 8 of
      gestation, pregnant rats were treated orally with these compounds at 80 mumol/kg,
      or with 3-OHDBTL at 80 or 160 mumol/kg. Cesarean sections were performed on day
      20 of gestation and fetuses were examined for their external and skeletal
      anomalies. Types of the observed malformations were similar to those in the
      previous study with DBTA except 3-OHDBTL, though the incidence of fetuses with
      malformations was different. In the DBTC-treated group, skeletal anomalies were
      predominant to external ones, especially with the higher incidence of fused ribs
      than in the other groups. In the 3-OHDBTL-treated group, no external and skeletal
      anomalies were observed at 80 mumol/kg and cleft lower lip and ankyloglossia were
      observed in only one fetus, but peaked mandible (the tip of lower jaw with acute
      angle) was specific at 160 mumol/kg. From these results, the di-n-butyl group
      rather than anionic group was found to be important in the teratogenicity of di-n
      butyltin compounds as well as in the other kinds of toxicities and 3-OHDBTL, one
      of the main metabolites of DBTL, is not the critical substance of teratogenicity
      because of a very low teratogenic potency.

PMID- 8303711
TI  - Immunomodulatory activities of extracellular metallothionein. I. Metallothionein
      effects on antibody production.
AB  - Extracellular metallothionein (Zn,Cd-MT) has previously been shown to be a potent
      inducer of lymphocyte proliferation and to synergize with polyclonal activators
      in proliferation assays. In this report, the effects of metallothionein on the
      development of humoral responsiveness are examined. In vivo, the specific anti
      ovalbumin (OVA) IgG response was diminished by co-injection of Zn, Cd-MT, while
      total IgG levels remained unchanged. A similar reduction was also observed when
      Zn,Cd-MT was administered during the development of an anti-sheep red blood cell
      (sRBC) humoral response. When amounts of Zn and Cd equimolar to that associated
      with the Zn, Cd-MT were co-injected with OVA, humoral responsiveness was
      enhanced, in contrast to the suppression seen with Zn, Cd-MT. Apothionein lacking
      the available thiols associated with native Zn, Cd-MT had no effect on the
      development of humoral immunity. These results point to the thiols associated
      with the protein as the important determinants in the observed immunosuppression
      and this is supported by the capacity of UC1MT, a new monoclonal anti-MT
      antibody, to reverse MT mediated immunosuppression. No evidence was found to
      suggest that Zn,Cd-MT was interacting directly with OVA. Finally, in vitro
      experiments with LPS-stimulated splenocyte production of IgM correlated with the
      in vivo observations of Zn,Cd-MT. These data provide evidence for a significant
      role for MT in the development of metal-mediated immunomodulation and suggest
      that MT may also possess immunomodulatory functions under circumstances where MT
      is synthesized in the absence of heavy metal stress. Furthermore, it may be
      possible to take advantage of this system to exogenously manipulate the
      development of the immune response.

PMID- 8303712
TI  - Evaluation of the developmental toxicity of citrinin using Hydra attenuata and
      postimplantation rat whole embryo culture.
AB  - Citrinin (a mycotoxin produced as a frequent contaminant of food and feed by
      numerous species of Aspergillus and Penicillium fungi) is embryo/fetotoxic and
      embryocidal in mice and rats. The present study was designed to examine whether
      the in vivo observed developmental toxicity of citrinin could be recapitulated
      using the Hydra attenuata (HA) bioassay and then be confirmed in rat whole embryo
      culture (WEC). Results from the HA assay indicated that the minimal affective
      concentrations of citrinin required to elicit a toxic response in the adult hydra
      (MACA) and in the regenerating hydra (MACD) were 30 mg/l and 20 mg/l,
      respectively. The Hydra developmental hazard index (A/D ratio) was equal to 1.5,
      classifying citrinin as a coaffective developmental toxin. In WEC, rat embryos
      were cultured in homologous (rat) serum containing citrinin at various
      concentrations ranging from 0.0 and 300 micrograms/ml for a period of 45 h. The
      results indicated a concentration-dependent reduction in yolk sac diameter, crown
      rump length, somite number, protein and DNA contents. No embryonic
      dysmorphogenesis was observed in any treatment group. Histological examination
      revealed severe diffuse mesodermal and ectodermal necrosis in embryos treated
      with 250 micrograms/ml citrinin. At lower concentrations of citrinin, embryos
      were neither grossly nor histologically different from controls. Both the HA and
      WEC bioassays demonstrated that citrinin is not a primary developmental toxin.
      The use of HA and WEC bioassays in tandem may facilitate the rapid detection and
      ranking of the developmental hazards of food and feedborne mycotoxins.

PMID- 8303713
TI  - Drug-induced lysosomal storage of sulfated glycosaminoglycans. Studies on the
      underlying structure-activity relationships.
AB  - Some immunomodulatory drugs have previously been shown to induce lysosomal
      storage of sulfated glycosaminoglycans (sGAG) in intact organisms and cultured
      cells. These compounds consist of a planary aromatic ring system and two
      symmetric side chains each carrying a protonizable nitrogen. The purpose of this
      study was to test a larger collection of such compounds for their potencies to
      induce lysosomal storage of sGAG in cultured fibroblasts of rat cornea. The cells
      were exposed (72 h) to various compounds differing with respect to the aromatic
      ring system or the side chains. Lysosomal sGAG-storage was demonstrated by
      selective cytochemical staining with cuprolinic blue. The threshold
      concentration, i.e., the concentration necessary to induce cuprolinic blue
      positive cytoplasmic inclusions in at least 1% of the cells, was determined for
      each compound. The threshold concentrations were distributed over a range of 0.3
      30 microM. It should be emphasized that the threshold concentration of a given
      compound is not a constant, but depends on the volume of cell culture medium per
      surface area of cell monolayer, since the lysosomal accumulation lowers the
      initial drug concentration in the medium. If the ratio of medium volume:cell
      monolayer surface is increased as compared with standard cell culture conditions,
      the threshold concentration will be lowered. The compounds were ranked according
      to their threshold concentrations as determined under standard conditions. The
      following conclusions can be drawn from the ranking: the type of the central
      aromatic ring system and the distance between the ring system and the
      protonizable nitrogen atoms of the side chains influence the potency to induce
      lysosomal sGAG-storage. Regarding the ring system, the potency decreases as
      follows: acridine approximately anthrachinone > fenfluorenone approximately
      fenfluorene > xanthenone; xanthene > dibenzofuran approximately dibenzothiophene.
      In intact organisms, these structure-activity relationships may be superimposed
      by drug metabolism and pharmacokinetic factors.

PMID- 8303714
TI  - Effect of L-ascorbic acid pretreatment on cadmium toxicity in the male Fischer
      (F344/NCr) rat.
AB  - Some studies have indicated that cadmium-induced lethality and selective
      injurious effects to specific tissues, such as testes or liver, can be prevented
      by pretreatment with the antioxidant L-ascorbic acid (ascorbic acid). However,
      the basis of this tolerance is unclear. We examined the effects of ascorbic acid
      pretreatment on cadmium toxicity in male Fischer (F344/NCr) rats. Cadmium
      treatment alone (25 mumol CdCl2/kg, s.c.) proved lethal, causing a 93% mortality
      within 72 h, but in rats pretreated with ascorbic acid (2 g/kg, s.c. 24, 12 and 1
      h) cadmium-induced lethality was nearly prevented. Hepatic lesions, including
      hepatocellular necrosis, induced by cadmium were at least partially ameliorated
      by ascorbic acid pretreatment. Ascorbic acid pretreatment had no effect on
      cadmium-induced testicular lesions nor on cadmium content in testes, liver,
      kidney and urine. Ascorbic acid alone modestly increased hepatic metallothionein
      (MT), but not renal MT and had no effect on induction of hepatic or renal MT by
      cadmium. In contrast to liver and kidney, testicular cadmium-binding protein
      (TCBP) in rats exposed to cadmium alone decreased markedly. Moreover, the level
      of TCBP decreased unexpectedly in ascorbic acid pretreated rats as compared with
      control. These results indicate that ascorbic acid pretreatment decreases the
      toxicity of cadmium in the rat without markedly modifying its toxicokinetics or
      markedly stimulating MT synthesis.

PMID- 8303715
TI  - Purification of a capillary permeability-increasing enzyme-2 from the venom of
      Agkistrodon caliginosus (Kankoku-Mamushi).
AB  - A capillary permeability-increasing enzyme-2 was purified from the venom of A.
      caliginosus by ion-exchange chromatography and gel filtration on Sephadex G-100.
      By this procedure, 3.1 mg of purified enzyme was obtained from 4 g of the venom.
      The mol. wt of the purified enzyme was estimated to be approximately 44,000 by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme hydrolyzed
      N-alpha-tosyl-L-arginine methylester with a specific activity of 56.5 units/mg of
      protein, and did not show any caseinolytic, clotting or bradykinin-releasing
      activity. When 13.9 micrograms of the enzyme was injected into the depilated skin
      on the back of a rabbit, capillary permeability was increased.

PMID- 8303716
TI  - Some properties of a capillary permeability-increasing enzyme-2 from the venom of
      Agkistrodon caliginosus (Kankoku-Mamushi).
AB  - Capillary permeability-increasing enzyme-2 (CPI-enzyme-2) consists of a single
      polypeptide chain with an isoelectric point of pH 3.5. The enzyme is composed of
      369 amino acid residues, based on a mol. wt of 44,000, and contains 20.3%
      carbohydrate. Both arginine ester hydrolytic and capillary permeability
      increasing activities of the enzyme were inhibited by treatment with
      diisopropylfluorophosphate, indicating that the enzyme is a serine proteinase.
      The N-terminal amino acid sequence shows homology with that of CPI-enzyme-1 and
      similarity to those of batroxobin or kallikrein-like enzyme from other snake
      venoms.

PMID- 8303717
TI  - Effects of different antagonists on depolarization of cultured chick myotubes by
      cobra venom cardiotoxins and Pyrularia thionin from the plant Pyrularia pubera.
AB  - Cardiotoxins (3.12 and 3.12.1) purified from cobra venom (Naja naja siamensis)
      are basic single-chain polypeptides of about 60 residues. Although they
      depolarize nerve and muscle cells and have cytolytic effects, their mechanism of
      action is still unknown. Pyrularia thionin (P-thionin) isolated from nuts of the
      parasitic plant Pyrularia pubera is a strongly basic, single-chain polypeptide
      containing 47 residues. It is known to be haemolytic and cytotoxic, and to
      depolarize muscle cells, but its mechanism of action is unclear. The present
      studies explored the possible similarities between P-thionin and cobra venom
      cardiotoxins by comparing their effects on depolarization of cultured chick
      skeletal muscle cells in the presence and absence of possible antagonists.
      Cardiotoxins and P-thionin depolarized cultured chick skeletal muscle cells, but
      with P-thionin showing a steeper concentration-dependence. Ca2+ was more
      effective at reducing cardiotoxin action than P-thionin, while the Ca(2+)-channel
      blockers Ni2+ (100 microM) and verapamil (100 microM) had no blocking effects on
      the toxins. Ca2+ may block the binding of both toxins. Indomethacin (100 microM,
      an inhibitor of cyclooxygenase), quinacrine and dexamethasone (100 microM,
      inhibitors of phospholipase A2) did not block the effects of the toxins, implying
      that the actions on cultured chick skeletal muscle cells are not due to
      activation of endogenous phospholipase A2.

PMID- 8303718
TI  - Effect of Bothrops insularis venom on the mouse and chick nerve-muscle
      preparation.
AB  - The effects of Bothrops insularis venom were examined in vivo in mice and chicks
      and in vitro using the mouse phrenic nerve diaphragm and chick biventer cervicis
      muscle preparations. Incubation of the indirectly or directly stimulated mouse
      preparation with B. insularis venom (20-80 micrograms/ml) produced an initial
      increase in twitch tension followed by irreversible blockade. With direct
      stimulation in the presence of D-tubocurarine, no increase in twitch tension was
      observed prior to the onset of blockade. A venom-induced effect on presynaptic
      activity was suggested by the marked increase in the frequency of the mepps
      recorded in vitro 5-15 min after venom addition. A direct muscular effect was
      shown by the dose- and time-dependent reduction in the resting membrane potential
      of the diaphragm. Chick preparations were more sensitive than those of the mouse.
      In the isolated chick biventer cervicis muscle preparation, B. insularis venom
      induced a contracture and a dose-dependent block of responses to indirect
      stimulation. At low venom concentrations (1-5 micrograms/ml), no significant
      release of creatine kinase (CK) was observed from this preparation. However, a
      dose-dependent release of CK was detected at higher doses (10-80 micrograms/ml).
      For morphological studies, B. insularis venom was injected into the chick left
      pectoralis muscle. At low doses (0.4 microgram), only an inflammatory reaction
      was present, while at high doses (20-80 micrograms) increasing numbers of
      necrotic fibers were observed as well as occlusive thrombosis and hemorrhage. The
      muscular effect, also observed on the incubated muscle, points to a direct
      myolytic action of the whole venom.

PMID- 8303719
TI  - Evidence of mammalian Ca2+ channel inhibitors in venom of the spider Plectreurys
      tristis.
AB  - Plectreurys tristis venom inhibited K(+)-stimulated Ca2+ influx in a
      concentration-dependent manner in rat (0.5-4.0 micrograms venom protein/ml) and
      chicken (1.0-64.0 micrograms venom protein/ml) brain synaptosomes. In contrast to
      Hololena curta venom or omega conotoxin GVlA which both show selectivity for
      avian synaptosomes, inhibition of Ca2+ influx by the venom appeared to be
      relatively selective for rat synaptosomes. Plectreurys tristis venom also
      inhibited K(+)-evoked release of [3H](-)-noradrenaline from labeled rat cortical
      synaptosomes. Responses to electric field stimulation of the sympathetically
      innervated rat vas deferens in vitro were inhibited by Plectreurys tristis venom
      at dilutions similar to those which inhibited Ca2+ influx in synaptosomes.
      Inhibition persisted following washout of the venom. K(+)-evoked contractions of
      rat aortic rings were relaxed by the dihydropyridine antagonist (-)-202-791, but
      not by Plectreurys tristis venom, thus precluding an effect on K(+)-depolarized
      smooth muscle L-type channels. Contractions to exogenous (-)-noradrenaline in rat
      aorta were not inhibited by Plectreurys tristis venom, ruling out an effect on
      alpha 1-adrenergic receptors, and further suggesting a prejunctional site of
      action. The results suggest that this venom inhibits N-type Ca2+ channels, as
      well as unclassified Ca2+ channels, which are neither N- nor L-type.

PMID- 8303720
TI  - Analgesic effect evoked by low molecular weight substances extracted from
      Crotalus durissus terrificus venom.
AB  - Crude venom obtained from Crotalus durissus terrificus (Cdt) was tested for its
      possible analgesic effect in mice. Subcutaneous (s.c.), intraperitoneal (i.p.) or
      oral (p.o.) administration of the venom caused an antinociceptive effect in mice
      as measured by the acetic acid-induced writhing method and the hot plate test.
      The antinociceptive activity was dose and time dependent and persisted after
      neutralization of the venom with a specific antivenin. It was demonstrated that
      the factor(s) has an apparent mol. wt of less than 3000 and that its
      antinociceptive effect is abolished by trypsin treatment. The demonstration that
      morphine enhances the analgesic effect of Cdt venom and naloxone antagonizes this
      effect suggests an endorphin-like activity for the factor(s) herein described.

PMID- 8303721
TI  - Effects of myonecrotic snake venom phospholipase A2 toxins on cultured muscle
      cells.
AB  - We have attempted to establish a cell culture model suitable for molecular
      mechanism of action studies of necrotic phospholipases A2 (PLA2). Three
      myonecrotic PLA2 were purified, one basic PLA2 from Naja nigricollis venom and
      two basic PLA2 (VRV-PL-V and VRV-PL-VIIIa) from Vipera russelli venom. The
      effects of these PLA2 on several established muscle cell lines were evaluated. As
      judged by light microscopy, some, but not all, cell lines detached from the
      culture plate in a time- and concentration-related fashion. Naja nigricollis PLA2
      was the most potent at eliciting this effect, followed by VRV-PL-V and VRV-PL
      VIIIa. The two most sensitive cell lines, 1447 and 1456, were chosen for further
      study using N. nigricollis PLA2. Cellular protein and nucleic acid syntheses were
      inhibited by the toxin in a time- and dose-related manner. However, it appeared
      that most, if not all, of the inhibition was due to toxin-induced reduction of
      precursor uptake, suggesting effects at the plasma membrane level. The putative
      membrane effects were specific, in that uptake of calcium, choline or glucose was
      not inhibited by the toxin. Moreover, treating the cells with toxin failed to
      significantly increase lactate dehydrogenase release into the medium. Polyclonal
      antiserum prepared against N. nigricollis basic PLA2 neutralized the toxicity
      completely with 1456 cells, but only partially with the 1447 cell line. Both the
      1447 and 1456 lines appear to be suitable as cell culture models for necrotizing
      PLA2 molecular mechanism of action studies.

PMID- 8303722
TI  - Purification and activation of phospholipase A2 isoforms from Naja mossambica
      mossambica (spitting cobra) venom.
AB  - Isoforms of phospholipase A2 (PLA2) from the venom of Naja mossambica mossambica
      (the spitting cobra) were purified by a combination of gel filtration on Bio-gel
      P-30 and ion exchange chromatography on DE-52 Cellulose and the purification
      followed by three types of polyacrylamide gel electrophoresis. SDS PAGE failed to
      resolve the active band into separate isoforms. Acid/urea PAGE, resolved the
      peptides and major protein components of the venom and was able to separate two
      PLA2 bands in the whole venom. Alkali/urea PAGE resolved four PLA2 bands in whole
      venom, but could resolve six distinct purified PLA2 species. Of the known
      isoforms, the acidic form (CM-1) was purified to homogeneity. The basic non-toxic
      isoform (CM-II) was shown to migrate as a close doublet of PLA2 isoforms. A novel
      minor purified isoform was identified with mobility intermediate between CM-I and
      the basic non-toxic isoform CM-II. CM-III was shown to contain a minor PLA2
      contaminant. The analysis was facilitated by the fact that all of the isoforms
      could be eluted from the gels with > 60% recovery of activity. The venom
      therefore contains at least six isoforms of PLA2 which differ largely by their
      content of acidic acids. Oleoyl imidazolide treatment increased the haemolytic
      activity of all but the toxic PLA2 isoform in Naja mossambica mossambica, but
      partially inhibited the catalytic activity of acidic, toxic and newly purified
      isoforms whilst partially activating the non-toxic isoform.

PMID- 8303723
TI  - Characteristics of the peptidase activity contained in Taiwan cobra (Naja naja
      atra) venom.
AB  - Cobra venoms (Naja species) contain a little-understood peptidase activity which
      shows specificity towards small peptides containing glycine and non-polar
      aromatic/aliphatic residues. We have examined the ability of whole cobra venom to
      degrade several types of peptide with emphasis on the action of Taiwan cobra
      (Naja naja atra) venom on L-alanylglycylglycine and glycylglycyl-L-phenylalanine.
      These are competing substrates, and it proved possible to generate inhibitors of
      the degradation of glycylglycyl-L-phenylalanine by synthesizing L
      alanylglycylglycine analogues in which the peptide bond between the second and
      third residues had been replaced by different linkages. These analogues were
      themselves resistant to hydrolysis. The peptidase activity can also be inhibited
      by bestatin, captopril and chloromethyl ketones. Kinetic analyses suggested that
      even the best substrate discovered was of poor efficacy, so the natural peptide
      substrate remains to be identified. In unsuccessful attempts to devise a reliable
      chromogenic assay, it was found that the venom had activity against N-blocked
      amino acid p-nitrophenol esters, but not against leucine p-nitroanilide or ester
      substrates for trypsin-like and chymotrypsin-like enzymes.

PMID- 8303724
TI  - The black scorpion Heterometrus longimanus: pharmacological and biochemical
      investigation of the venom.
AB  - Documentation on the biological activity (including the lethality) of the venom
      (BSV) from the black scorpion Heterometrus longimanus is lacking. We have
      investigated the effects of BSV on adrenergic transmission using the rat isolated
      anococcygeus muscle (Acm), since the venom from several species of scorpions
      causes peripheral sympathetic nerve stimulation with enhanced adrenergic
      responses. The catecholamine content in BSV was also measured by HPLC. The
      effects of phentolamine (5 microM), guanethidine (5 microM), desipramine (1.5
      microM), tetrodotoxin (2 microM) and reserpine pretreatment in vivo (5 mg/kg s.c.
      x 24 hr and 5 mg/kg i.p. x 3 hr) on contractile responses of the rat Acm to field
      stimulation, crude BSV (2-10 microliters in 6 ml bath), noradrenaline (3 microM),
      tyramine (10-15 microM), carbachol (2-3 microM) and potassium chloride (50-75 mM)
      were investigated. BSV mimicked the agonist actions of noradrenaline (NA) by
      acting directly on postjunctional alpha-adrenoceptors in the anococcygeus muscle.
      The LD50 of crude BSV injected i.v. into mice was 0.13 ml per kg mouse.
      Sequential ultrafiltration of the crude BSV revealed the presence of a substance
      of low mol. wt which mediates the postjunctional alpha-agonist actions of BSV.
      HPLC measurements confirmed the presence of noradrenaline (NA; mean concentration
      of 1.8 +/- 0.3 mM) in BSV; the dopamine concentration (mean of 31 +/- 4 microM)
      was 60-fold lower than that of NA, whereas adrenaline was not detected in all the
      15 samples investigated. Thus, the presence of NA in BSV can account for the
      postjunctional alpha-agonist actions of the venom in the Acm.

PMID- 8303725
TI  - Chemical and biological evidence links microcystins to salmon 'netpen liver
      disease'.
AB  - Evidence is presented that links microcystins to a severe liver disease that
      occurs in Atlantic salmon that are netpen-reared in coastal British Columbia.
      Liquid chromatography-linked protein phosphatase bioassay analysis of extracts of
      liver tissue taken from Atlantic salmon afflicted with netpen liver disease
      showed the presence of an inhibitor of protein phosphatase that was
      chromatographically indistinguishable from microcystin-LR. Analysis of liver
      tissue from healthy control fish showed a complete absence of microcystin-LR.
      Intraperitoneal injection of microcystin-LR into healthy Atlantic salmon re
      created the pathologic changes of netpen liver disease, including diffuse
      necrosis and hepatic megalocytosis.

PMID- 8303726
TI  - A modification of the ELISA-double sandwich method for estimating the
      concentration of habutobin.
AB  - A monoclonal antibody to the thrombin-like enzyme, habutobin, was produced. An
      ELISA-double sandwich method employing this monoclonal antibody was devised as a
      method for determining the habutobin concentration in vitro. However, the
      absorbance of the control sample in such an ELISA-double sandwich procedure was
      too high to estimate low levels of the enzyme. The present study therefore
      attempted to establish a reliable ELISA-double sandwich method in which the
      absorbance of the control sample was lower than previously, and which had a high
      sensitivity, in order to determine the habutobin concentration in vitro and in
      vivo. The modification of the ELISA-double sandwich technique employing the
      monoclonal antibody against habutobin, the purified rat IgG against habutobin and
      POD-mouse anti-rat IgG2a, provided a reliable means of determining the habutobin
      levels in the circulating blood of rabbits.

PMID- 8303727
TI  - Effect of toxins 544 and 514 from Karwinskia humboldtiana (buckthorn) plant upon
      fetal development of the mouse.
AB  - The teratogenic effect of toxins 544 and 514 from K. humboldtiana upon the mouse
      embryo was evaluated. One half of the LD50 dose for the mouse was administered at
      day 8 of gestation. At the end of pregnancy, reproduction and fetal data were
      recorded. Dams treated with toxin 544, but not with toxin 514, showed a higher
      incidence of reabsorptions, malformations, as well as lower fetal length compared
      to the control group.

PMID- 8303728
TI  - Recovery of ciguatoxin from fish flesh.
AB  - A mouse bioassay, validated for the quantification of ciguatoxin in up to 20 mg
      of ether extract from fish flesh, revealed that 63 +/- 14% of spiked ciguatoxin
      was recovered using a standard extraction procedure. Except for extracts from the
      least toxic of ciguateric fish (0.1-0.5 nmol ciguatoxin-1/kg fish), signs in mice
      of intoxication by ciguatoxin (hypothermia to below 33 degrees C as well as at
      least severe diarrhoea or lachrymation or hypersalivation) could be distinguished
      from the toxic reaction that follows administration of ciguatoxin-free ether
      extracts. Ciguatoxin recovery was similar for four variants of the ether-water
      partition, with the 2 M NaC1/ether partition extracting half the contaminants.
      The method described is selective for ciguatoxin and could be used to quantify
      natural levels ciguatoxin in the flesh of fish in the absence of a validated in
      vitro test.

PMID- 8303729
TI  - Solubility and stability of sterigmatocystin in different organic solvents.
AB  - In the present work we studied the solubility of sterigmatocystin (ST) in
      different organic solvents and the stability of these solutions during cold and
      frozen storage. ST was more soluble in chloroform and in pyridine. In cold
      storage ST was more stable in chloroform after both 7 and 30 days. In pyridine,
      ST was stable on day 7 but not on day 30. In frozen storage, 90% recovery was
      achieved only in chloroform. We conclude that chloroform is the most suitable
      organic solvent of those studied to solubilize and store standard solutions of
      ST.

PMID- 8303730
TI  - Failure of aspirin treatment after stroke.
AB  - BACKGROUND AND PURPOSE: Despite its low efficacy, aspirin is the most widely used
      drug for secondary stroke prevention. The reasons why stroke recurs while
      patients are on aspirin are unknown. We have analyzed a series of patients who
      had recurrent strokes while on aspirin. METHODS: Out of 2231 consecutive patients
      who were admitted to the Tel Aviv Medical Center from May 1988 through December
      1992 with the diagnosis of ischemic stroke, 129 admissions were due to recurrent
      ischemic strokes while the patients were already on aspirin, and these were
      defined as aspirin failures. The clinical characteristics of those patients in
      whom aspirin treatment failed were compared with three control groups, each
      comprising 129 patients who had had only a single ischemic stroke and were then
      taking aspirin. One control group was matched for aspirin dose and date of first
      stroke; another control group was matched for age, sex, and date of first stroke;
      and a third control group was matched for age, sex, date of first stroke, and
      aspirin dose. Statistical analysis was carried out by two-tailed Student's t test
      and chi 2 test. RESULTS: The average period until stroke was longer for patients
      on higher aspirin doses. Patients matched for aspirin dose and date of first
      stroke did not differ significantly in age (72.4 years in aspirin failures versus
      74.2 years in the first control group) and sex (89 versus 94 men, respectively).
      Matching for age, sex, and date of first stroke but not for aspirin dose
      demonstrated a trend toward high frequency of aspirin failure in patients taking
      lower doses of aspirin (chi 2 test for trend = 3.5; P = .06). Comparison of
      aspirin-failure patients with a control group matched for age, sex, date of first
      ischemic stroke, and aspirin dose demonstrated that these patients more commonly
      had statistically significant hyperlipidemia (odds ratio, 2.6; 95% confidence
      interval, 1.0 to 6.8; P = .04) and ischemic heart disease (odds ratio, 2.3; 95%
      confidence interval, 1.3 to 3.9; P = .002). CONCLUSIONS: We conclude that age and
      sex do not influence the efficacy of aspirin. Lower aspirin dose in patients with
      stroke recurrence suggests that aspirin doses of 500 mg daily or more should be
      used in secondary stroke prevention. Hyperlipidemia and ischemic heart disease
      are risk factors for stroke recurrence despite aspirin treatment, which requires
      further clinical and laboratory evaluation.

PMID- 8303731
TI  - Evidence for episodic platelet activation in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Enhanced thromboxane biosynthesis has previously been
      reported in patients with acute ischemic stroke. In this study we examined the
      time course of thromboxane biosynthesis after the onset of symptoms in 13
      patients with acute cerebral infarction. METHODS: We obtained five to eight
      consecutive 6-hour urine samples from each of these 13 patients within the first
      48 hours after onset of symptoms to study the dynamics of platelet activation in
      this setting. The urinary excretion of the major enzymatic metabolite of
      thromboxane B2, 11-dehydro-thromboxane B2, was measured by a previously validated
      radioimmunoassay. The excretion rate was compared with that of 20 control
      patients with nonvascular neurological diseases. RESULTS: Eleven patients (85%)
      had at least one value exceeding 2 SD of the control mean (251 pmol/mmol
      creatinine). The proportion of samples with an elevated 11-dehydro-thromboxane B2
      level was markedly similar in each of the eight 6-hour collection periods (mean,
      52 +/- 8%; range, 40% to 67%). In 4 patients (31%) the excretion rate was
      elevated in all measurements obtained. In the 11 patients with enhanced
      thromboxane biosynthesis, no uniform pattern of changes over time in metabolite
      excretion emerged, with 3 patients having peak values at 0 to 12 hours, 3 at 12
      to 24 hours, 3 at 24 to 36 hours, and 2 at 36 to 48 hours. The level and dynamics
      of 11-dehydro-thromboxane B2 excretion were related neither to the neurological
      symptoms nor to the type or site of the cerebral ischemia. CONCLUSIONS: We
      conclude that episodes of platelet activation occur repeatedly during the first
      48 hours after the onset of symptoms of an acute ischemic stroke. Given its
      apparent dynamic nature, this ongoing process may be amenable to pharmacologic
      modulation.

PMID- 8303732
TI  - Hemostatic markers in acute transient ischemic attacks.
AB  - BACKGROUND AND PURPOSE: Hemostatic abnormalities have been shown previously in
      stroke patients. The purpose of this study was to assess the activity of selected
      parameters of the coagulation system in acute reversible cerebral ischemia.
      METHODS: We measured fibrinopeptide A, thrombin-antithrombin III, and D-dimer in
      36 patients in both the acute (< 7 days) and postacute stage (1 and 3 months)
      after a transient ischemic attack (TIA). The results were compared with those of
      20 asymptomatic patients with a history of remote TIA and 65 age- and sex-matched
      controls. RESULTS: Mean fibrinopeptide A and thrombin-antithrombin III values
      were elevated in the acute stage after a TIA (P < .02) compared with levels at 1
      month. In contrast, D-dimer was significantly increased at all three times points
      after the event when compared with remote TIA (P < .05) or control subjects (P <
      .001). No association could be found between marker levels and clinical outcome
      or the degree of cervical atherosclerosis as assessed by duplex ultrasonography.
      CONCLUSIONS: These findings suggest that after acute reversible cerebral
      ischemia, there is early transient activation of thrombogenesis and ongoing
      fibrinolysis.

PMID- 8303733
TI  - Prothrombotic states in young people with idiopathic stroke. A prospective study.
AB  - BACKGROUND AND PURPOSE: Although 4% of cerebral infarcts in the young can be
      attributed to hematologic disturbances that predispose to thrombosis, the
      frequency of cerebral infarcts caused by prothrombotic states is not known.
      Recently, the association between cerebral infarction and deficiencies of
      elements of the natural anticoagulant system has been recognized. METHODS: Thirty
      six consecutive patients under 40 years of age with cerebral infarction of
      undetermined cause were prospectively studied. Quantitation of natural
      anticoagulants was done at least 3 months after the cerebral infarction. The
      following activity tests were performed, all by the chromogenic method:
      antithrombin III, protein C, plasminogen, tissue plasminogen activator, and
      inhibitor of tissue plasminogen activator. Protein S was quantified by the
      Laurell rocket method. All patients underwent a complete cardiological
      examination, including two-dimensional echocardiography, as well as four-vessel
      cerebral angiography. Some patients were also studied by transesophageal
      echocardiography. RESULTS: Of 36 patients, 17 were male, with a mean age of 28
      years. Mean age for women was 25 years. Nine patients (25%; 5 women, 4 men) had a
      deficiency of one natural anticoagulant and constituted group I. In these
      patients, isolated protein S deficiency was detected in five cases (13.8%); in
      one case, we observed the association between protein S deficiency and
      antiphospholipid antibodies; and deficiency of protein C was seen in one case
      (2.7%), of antithrombin III in one case (2.7%), and of plasminogen in one case
      (2.7%). Instances of cerebral infarction without natural anticoagulant deficiency
      (group II) included 12 women and 15 men. There were no differences in clinical
      and radiological findings between the two groups. CONCLUSIONS: Considering the
      importance of prothrombotic state, especially caused by deficiency of protein S,
      in the development of cerebral infarcts, we suggest that it should be looked for
      in every young patient affected by this pathological entity and in whom no
      etiologic factors can be determined.

PMID- 8303734
TI  - Factors related to intracranial hematoma formation in patients receiving tissue
      type plasminogen activator for acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Several studies are currently evaluating tissue-type
      plasminogen activator (TPA) as a potential therapy in acute ischemic stroke. The
      possibility of inducing intracranial hematomas, however, introduces an important
      concern into ultimate evaluation of risk and benefit. This retrospective analysis
      sought to identify factors associated with intracranial hematoma formation in a
      pilot phase 1 study of TPA for stroke. METHODS: Ninety-four patients received TPA
      within 3 hours of the onset of an acute ischemic stroke. Five of these patients
      developed a symptomatic intracerebral hematoma: 3 of 74 (4%) among patients
      treated within 90 minutes of stroke onset and 2 of 20 (10%) among those treated
      at 91 to 180 minutes. Three of the 5 died within 2 weeks. The analysis
      investigated associations between clinical factors and intracerebral hematomas.
      RESULTS: Factors significantly related to the development of an intracerebral
      hematoma were TPA dose and diastolic hypertension. Intracerebral hematomas
      developed in 4 (18%) of 22 patients given a TPA dose of at least 0.90 mg/kg
      versus only 1 hematoma in the remaining 72 patients (1%; P < .02, Fisher's exact
      test). Four (18%) of 22 patients who had initial diastolic blood pressures of at
      least 100 mm Hg suffered an intracerebral hematoma versus only 1 (1%) of 72
      patients (P < .02) with lower initial diastolic pressures. CONCLUSIONS: Since the
      study was not designed to test specific safety hypotheses, results must not be
      overinterpreted. Nonetheless, these data emphasize the need for caution in both
      patient and dose selection for further studies of thrombolytic agents in stroke.

PMID- 8303735
TI  - Evaluation of risk of hemorrhagic transformation in local intra-arterial
      thrombolysis in acute ischemic stroke by initial SPECT.
AB  - BACKGROUND AND PURPOSE: Thrombolytic therapy was carried out on patients with
      acute ischemic stroke, and the risk of hemorrhagic transformation was evaluated
      from the residual cerebral blood flow (CBF) by pretherapeutic single-photon
      emission-computed tomography (SPECT). METHODS: Local intra-arterial thrombolytic
      therapy was carried out using urokinase or recombinant tissue plasminogen
      activator (rt-PA) within 6 hours from the onset in 34 patients in whom no
      hypodensity areas were observed on the initial computed tomography examination.
      In the 20 patients with carotid territory occlusion who underwent 99mTc-labeled
      hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT, the residual CBF of the
      ischemic region was evaluated semiquantitatively by calculating two parameters:
      the ischemic regional activity to cerebellar activity ratio (R/CE ratio) and
      asymmetry index (AI). RESULTS: The occluded vessels could be recanalized in 22
      (92%) of the 24 patients in the urokinase group and in all 10 of the patients in
      the rt-PA group. Hemorrhagic transformation appeared in 4 patients in the
      urokinase group and 3 patients in the rt-PA group. Among the 20 patients who
      underwent SPECT before the treatment, the residual CBF was lower in the 5
      patients who developed hemorrhagic transformation than in the 15 who did not (P <
      .05). Hemorrhagic transformation occurred in all patients with R/CE ratio of less
      than 0.35 and AI of more than 1.5. CONCLUSIONS: The risk of hemorrhagic
      transformation after recanalization of occluded vessels by local intra-arterial
      thrombolytic therapy was considered to be high when the pretherapeutic residual
      CBF was markedly reduced.

PMID- 8303736
TI  - Significance of plaque ulceration in symptomatic patients with high-grade carotid
      stenosis. North American Symptomatic Carotid Endarterectomy Trial.
AB  - BACKGROUND AND PURPOSE: The importance of carotid plaque ulceration as a cause of
      cerebral ischemic symptoms remains uncertain. Moreover, its prominence in
      symptomatic patients with severe carotid stenosis is unknown. METHODS: The
      association between angiographically defined plaque ulceration and risk of
      subsequent stroke was assessed using Cox proportional hazards regression in 659
      patients with severe (70% to 99%) carotid stenosis from the North American
      Symptomatic Carotid Endarterectomy Trial. RESULTS: Treatment assignment (medical
      versus surgical) and degree of ipsilateral stenosis were identified as having a
      significant influence on the results. The risk of ipsilateral stroke at 24 months
      for medically treated patients with ulcerated plaques increased incrementally
      from 26.3% to 73.2% as the degree of stenosis increased from 75% to 95%. For
      patients with no ulcer, the risk of stroke remained constant at 21.3% for all
      degrees of stenosis. The net result yielded relative risks of stroke (ulcer
      versus no ulcer) ranging from 1.24 (95% confidence interval, 0.61 to 2.52) to
      3.43 (95% confidence interval, 1.49 to 7.88). Conversely, for surgically treated
      patients with antecedent presence of an ulcerated plaque, the risk of stroke
      increased slightly at the highest degrees of stenosis. Overall, carotid
      endarterectomy reduced the risk of ipsilateral stroke at 24 months by at least
      50%. Similar results were obtained for risk of major ipsilateral stroke and risk
      of all strokes and death. CONCLUSIONS: The presence of angiographically defined
      ulceration for medically treated symptomatic patients is associated with an
      increased risk of stroke. The risk of stroke more than doubles at higher degrees
      of stenosis. Carotid endarterectomy is beneficial in substantially reducing the
      risk of stroke, regardless of plaque ulceration and degree of severe carotid
      stenosis.

PMID- 8303737
TI  - Relation of cerebral blood flow to motor and cognitive functions in chronic
      stroke patients.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to examine the levels of
      cerebral blood flow in relation to motor and cognitive functions in 300 chronic
      unilateral stroke patients (age, 64 +/- 12 years; mean +/- SD). METHODS: Cerebral
      blood flow was measured by the 133Xe inhalation method, adjusted for age, sex,
      and PCO2 level. Motor function was scored according to Brunnstrom hemiplegic
      staging and cognitive function according to the Hasegawa dementia rating scale
      tested in Japanese. RESULTS: Asymmetries of blood flow between affected and
      nonaffected hemispheres increased with lesion size and were highest in 11 embolic
      strokes (20 +/- 9%) and higher in 80 nonembolic cortical infarctions (11 +/- 11%)
      and 76 hemorrhages (9 +/- 7%) than in the group of 133 subcortical infarctions (2
      +/- 6%) or 16 control subjects (1 +/- 2%). Severity of hemiparesis correlated
      with decreased cerebral blood flow in the affected hemisphere (P < .01) and
      increased hemispheric asymmetries of blood flow (P < 001). Cognitive impairments,
      after adjusting for age, correlated with decreased cerebral blood flow in the
      nonaffected hemisphere (P < .0001), left hemispheric lesions (P < .0005), and
      embolic stroke (P < .005) but not with asymmetries of blood flow. Among 67
      patients having bilateral reductions of cerebral blood flow, 25 patients with
      left hemispheric lesions showed more severe cognitive impairments than among 42
      patients with right hemispheric lesions (P < .05). CONCLUSIONS: We confirmed that
      severity of hemiparesis correlated with the degree of asymmetries of cerebral
      blood flow, reflecting the extent and location of the lesions. Bilateral
      reductions of cerebral blood flow in patients with left hemispheric lesions may
      in part contribute to cognitive impairments, indicating reductions of global
      neuronal activities in the contralateral hemisphere or diffuse cerebrovascular
      changes. Further studies of cerebral metabolism and follow-up of cerebral
      circulation are required to reveal the pathophysiology and clinical consequences.

PMID- 8303738
TI  - Magnetic resonance abnormalities and cardiovascular disease in older adults. The
      Cardiovascular Health Study.
AB  - BACKGROUND AND PURPOSE: Cerebral magnetic resonance imaging often detects
      abnormalities whose significance is unknown. The prevalence and correlates of
      findings such as ventricular enlargement, sulcal widening, and increased white
      matter signal intensity were examined in 303 men and women aged 65 to 95 years
      participating in a multicenter study of cardiovascular disease. METHODS: Cerebral
      magnetic resonance imaging was performed and interpreted according to a standard
      protocol, and findings were correlated with measures of cardiovascular disease
      and its risk factors. RESULTS: Measures of cerebral atrophy increased with age
      and were greater in men than in women (each P < .01). Ventricular enlargement and
      sulcal widening were associated with prior stroke, hypertension, diabetes, and
      white race (each P < .03). Extent of white matter hyperintensity was associated
      with age, prior stroke, hypertension, and use of diuretics (each P < .004). On
      multivariate analysis, age, male gender, white race, and prior stroke retained
      strong associations with increased ventricular and sulcal scores. After
      adjustment for age, prior stroke, and other risk factors, white matter
      hyperintensity was associated with atherosclerosis as measured by increased
      internal carotid artery thickness on ultrasound. CONCLUSIONS: Cerebral atrophy
      and white matter hyperintensity are common in the elderly and are associated with
      age, prior stroke, and known cardiovascular risk factors. Though these findings
      have been suggested to represent normal aging, their wide variability and
      associations with cardiovascular disease argue against their inevitability with
      advancing age and support the need to identify modifiable risk factors for these
      abnormalities.

PMID- 8303739
TI  - Fish consumption and risk of stroke. The Zutphen Study.
AB  - BACKGROUND AND PURPOSE: A low-to-moderate average daily fish consumption has been
      reported to convey protection against coronary heart disease incidence and
      mortality. Currently there is no information about its effect on stroke risk.
      METHODS: In 1960, 1965, and 1970 cross-check dietary histories were obtained in
      552 men aged 50 to 69 years in 1970 in the town of Zutphen, The Netherlands. The
      association between fish consumption and stroke incidence in the period 1970 to
      1985 was assessed by Cox proportional hazards models. Adjustments were made for
      confounding by age, systolic blood pressure, cigarette smoking, serum total
      cholesterol, energy intake, alcohol consumption, and prescribed diet. RESULTS:
      The mean fish consumption in 1970 was 17.9 g/d. Men who consumed more than 20 g
      of fish per day in 1970 had a reduced risk of stroke compared with those who
      consumed less fish. The hazard ratio (HR) amounted to 0.49 (95% confidence
      interval [CI], 0.24 to 0.99), and did not change after adjustment for potential
      confounders. Fewer strokes occurred among the 301 men who always reported fish
      consumption between 1960 and 1970 than among the men who changed fish consumption
      habits between 1960 and 1970 or did not consume fish at all (HR, 0.63; 95% CI,
      0.34 to 1.16). CONCLUSIONS: These results suggest that consumption of at least
      one portion of fish per week may be associated with a reduced stroke incidence.

PMID- 8303740
TI  - Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire
      Community Stroke Project.
AB  - BACKGROUND AND PURPOSE: There have been few community-based studies of long-term
      prognosis after acute stroke. This study aims to provide precise estimates of the
      absolute and relative risks of stroke recurrence in an unselected cohort of
      patients with a first-ever stroke. METHODS: Six hundred seventy-five patients
      were registered in a community-based stroke register (the Oxfordshire Community
      Stroke Project) and prospectively followed for up to 6.5 years. Their relative
      risk of recurrent stroke was calculated using age- and sex-specific incidence
      rates for first stroke in Oxfordshire. RESULTS: One hundred eighty recurrent
      episodes of stroke were identified, of which 135 were first recurrences. Given
      survival, the actuarial risk of suffering a recurrence was 30% (95% confidence
      interval, 20% to 39%) by 5 years, about nine times the risk of stroke in the
      general population. The risk was highest early after the first stroke: 13% (95%
      confidence interval, 10% to 16%) by 1 year, 15 times the risk in the general
      population. After the first year the average annual risk was about 4%. The risk
      of stroke recurrence did not appear to be related to age or pathological type of
      stroke. CONCLUSIONS: The absolute and relative risks of recurrent stroke are
      highest early after the first stroke but remain elevated for several years
      thereafter. Efforts at secondary prevention should be initiated as soon as
      possible and continued for several years to gain greatest benefit.

PMID- 8303741
TI  - Association of occurrence of aneurysmal bleeding with meteorologic variations in
      the north of France.
AB  - BACKGROUND AND PURPOSE: Previous reports have established that the incidence of
      stroke may be influenced by meteorologic variations. However, no significant
      correlation was clearly demonstrated concerning aneurysmal bleeding. METHODS:
      From January 1, 1989, to December 31, 1991, 238 patients with angiographically
      confirmed diagnoses of subarachnoid hemorrhage were registered in the North of
      France region. For each day, the weather variables were provided by the national
      meteorologic office (Meteo France). We compared the meteorologic variables of
      days when subarachnoid hemorrhage occurred with the variables of days without
      subarachnoid hemorrhage in a multivariate model. RESULTS: We observed a seasonal
      pattern in the occurrence of subarachnoid hemorrhage, with a low frequency of
      rupture in June and July and maximum frequency in April and September (P < .05).
      The days of occurrence were associated with short duration of sunshine (P <
      .00006), low minimal level of hygrometry (P < .0002), low maximal temperature (P
      < .005), and low atmospheric pressure the day before the event (P < .05).
      CONCLUSIONS: Aneurysmal bleeding was significantly associated with weather
      variables. Cold-induced hypertension may explain these fluctuations in the
      occurrence of aneurysmal bleeding.

PMID- 8303742
TI  - A prospective reevaluation of transient ischemic attacks as a risk factor for
      death and fatal or nonfatal cardiovascular events.
AB  - BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) is generally considered a
      risk factor for death and cardiovascular events. This assumption is based on
      comparisons of the survival of the TIA population with that of the general
      population. Such comparisons may provide biased estimates of the risk associated
      with TIA because the general population is usually more healthy than TIA
      patients. METHODS: Using a prospective case-control study design, we report the
      comparison of a TIA population (n = 280) and a control group (n = 399) with a
      comparable cardiovascular risk factor burden. Proportional hazards analysis was
      used to compare survival time and time to fatal or nonfatal stroke and/or
      myocardial infarction for the two study groups. Comparisons were made without
      adjustment for risk factors and after adjustment for age, race, sex, and major
      cardiovascular risk factors. RESULTS: Before adjustment for age-race-sex or risk
      factors, TIA proved to be a risk factor for early mortality, stroke, and
      myocardial infarction (P < .05). Adjustment for age-race-sex disparities between
      the case and control groups explained much of the differences in mortality, as
      the hazard ratio was reduced from 2.2 to 1.4. However, adjustment for age-race
      sex or age-race-sex and risk factors did not markedly reduce the role of TIA as a
      risk factor for stroke or myocardial infarction. CONCLUSIONS: Although TIA proved
      to be a risk factor for stroke or myocardial infarction, it apparently plays a
      smaller role in the risk of death.

PMID- 8303743
TI  - Does age affect benefits of stroke unit rehabilitation?
AB  - BACKGROUND AND PURPOSE: The influence of age on benefits of stroke unit
      rehabilitation is largely unknown. METHODS: A prospective controlled study was
      undertaken in 245 stroke survivors randomized to a stroke unit or to general
      wards 2 weeks after stroke. Patients were divided into older (75 years and over)
      and younger (under 75 years) age groups, and their characteristics, prognosis,
      duration, and type of therapy input and outcome were compared in different
      settings. RESULTS: Younger (n = 101) and older (n = 144) stroke patients were
      comparable for neurological and functional deficits and were distributed equally
      between the stroke unit and general wards. The duration of therapy input was
      similar in younger patients in either setting. Older patients received more
      occupational therapy in both settings (10.7 +/- 2.4 versus 7.9 +/- 04.1) and more
      physiotherapy (18.4 +/- 9.6 versus 15.2 +/- 7.8) on general wards. Younger
      patients on the stroke unit showed better outcome compared with those on general
      wards (discharge home, 83% versus 60%; median Barthel score, 17 versus 13; median
      length of hospital stay, 27 versus 56 days) and with older patients on the stroke
      unit (discharge home, 83% versus 65%; median Barthel score, 17 versus 14).
      Outcome in older stroke patients was similar in both settings except for a
      shorter median length of hospital stay on the stroke unit (36 versus 84 days).
      Outcome in younger patients managed on general wards was worse than that in older
      patients with similar prognostic expectations (discharge home, 41% versus 61%;
      median Barthel score, 11 versus 13). CONCLUSIONS: Younger stroke patients
      benefited more by stroke unit rehabilitation compared with older patients, not
      only because of their age but also because of differences in the
      multidisciplinary input available for elderly patients outside the stroke unit.

PMID- 8303744
TI  - Predicting the disability of first-time stroke sufferers at 1 year. 12-month
      follow-up of a population-based cohort in southeast England.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to predict the functional
      outcome at 1 year of first-time stroke patients aged younger than 75 years in
      relation to the severity of stroke and demographic characteristics. METHODS:
      Population registers in three districts of southeast England were established in
      August 1989, with notification by stroke registry field-workers, general
      practitioners, and rehabilitation practitioners. Assessments were made using the
      Barthel index for activities of daily living at the time of maximum impairment
      and at 3 and 12 months after the stroke. RESULTS: Of 639 registered stroke
      patients, 392 without previous disability survived and were assessed for
      disability at 3 months, of whom 34 (9%) were severely disabled and 60 (15%)
      moderately disabled. Initial incontinence was the best single predictor of
      disability with a sensitivity of 60% and a specificity of 78%. Two hundred twenty
      five patients (35%) were eligible for 12-month follow-up; 11% had moderate or
      severe disability, for which initial incontinence was the best predictor.
      CONCLUSIONS: There is no evidence from this study of an association between
      demographic characteristics and the disability status of stroke survivors in the
      medium term. Multivariable predictors of disability had little advantage over
      incontinence within 24 hours of the stroke. The estimates of the prevalence of
      disability from this large population-based study are relevant when assessing the
      medium-term needs of stroke patients.

PMID- 8303745
TI  - Medical and neurological complications during inpatient stroke rehabilitation.
AB  - BACKGROUND AND PURPOSE: We sought to assess the type, frequency, and clinical
      predictors of neuromedical complications occurring during inpatient
      rehabilitation after stroke. METHODS: One hundred consecutive patient records
      were reviewed. All medical and neurological complications requiring a physician's
      order for further evaluation or treatment were recorded. RESULTS: Complications
      were urinary tract infection (44 cases), depression (33), musculoskeletal pain
      (31), urinary retention (25), falls (25), fungal dermatitis (24), hypotension
      (19), diabetes mellitus (16), hypertension (15), and other neuromedical problem
      (194). The mean +/- SD numbers of medical and neurological complications per
      patient were 3.6 +/- 2 and 0.6 +/- 0.8, respectively. Complications were
      independently related to both the severity of functional disability as judged by
      Barthel score (r = -.42, P < .001) and length of rehabilitation hospital stay (r
      = .54, P < .001). Cardiac complications were predicted by New York Heart
      Association class 3 or 4 symptomatology on admission (P < .05). The age, sex,
      interval from stroke to rehabilitation hospital admission, and ischemic versus
      hemorrhagic etiology of the stroke were unrelated to the number of complications
      observed. Thirteen patients required transfer back to an acute-care hospital, one
      of whom died within 24 hours of transfer. There were no deaths on the
      rehabilitation unit. CONCLUSIONS: We have defined the type and frequency of
      neuromedical complications during inpatient rehabilitation after stroke. Their
      frequency varies with the severity of stroke, cardiovascular comorbidity, and
      length of stay.

PMID- 8303746
TI  - Serial assessment of acute stroke using the NIH Stroke Scale.
AB  - BACKGROUND AND PURPOSE: The National Institutes of Health (NIH) Stroke Scale has
      been used in clinical trials to assess neurological outcome after investigational
      therapy for acute stroke. We used the NIH Stroke Scale to study the degree and
      time course of recovery in patients with acute stroke who were treated with
      conventional therapy. METHODS: We serially assessed 50 patients with ischemic
      stroke who presented within 24 hours of onset of symptoms. Patients were grouped
      by stroke subtype. Major neurological improvement was defined as a decrease in
      the stroke score by 4 points or more. RESULTS: The mean NIH stroke score for all
      patients improved significantly by 7 to 10 days and at last follow-up (average,
      44 days). Major neurological improvement was seen in 5 of 41 patients (12%; 95%
      confidence interval [CI], 2% to 22%) by 24 hours, 11 of 40 patients (28%; 95% CI,
      14% to 41%) by 48 hours, and 19 of 37 patients (51%; 95% CI, 35% to 67%) by
      follow-up. The subgroup of patients with middle cerebral artery territory
      embolism showed a similar pattern of improvement; in contrast, patients with
      lacunar infarcts did not show significant change in scores during the study
      period. The score on admission did not correlate with the degree of subsequent
      improvement or deterioration. CONCLUSIONS: A significant percentage of patients
      with acute ischemic stroke treated with conventional therapy show early
      improvement as assessed by the NIH Stroke Scale. The degree and time course of
      recovery may be influenced by stroke type.

PMID- 8303747
TI  - Feeding dependence and nutritional status after acute stroke.
AB  - BACKGROUND AND PURPOSE: We assessed the nutritional status of patients with acute
      stroke and evaluated it in relation to the patients' dependence on assistance
      with feeding. METHODS: Fifty patients aged 70 years or older, admitted from their
      homes, were included. Weight index, triceps skinfold thickness, arm muscle
      circumference, serum proteins, delayed hypersensitivity, body composition
      measured by bioelectric impedance, and functional condition were determined on
      admission and 2 and 9 weeks after admission. Food and fluid consumption were also
      recorded. RESULTS: On admission, four patients were regarded as protein-energy
      malnourished. Those who required assistance with feeding after admission (n = 18,
      36%) had lower serum albumin (P < .05), lower body cell mass (P < .01), and were
      more anergic than the independent patients (P < .01) on admission. The mean food
      consumption was 72% of the food served without significant difference between
      dependent and independent patients. Nine weeks after the onset of stroke
      symptoms, the patients who were dependent on assisted feeding showed a decrease
      in body cell mass. The loss of body cell mass was related to their activity and
      feeding dependence. CONCLUSIONS: Low serum albumin and anergy commonly occur in
      elderly patients with acute stroke, and they occur more prevalently among those
      with a severely impaired functional condition. During the recovery period, the
      patients use body fat to compensate for energy needs, and immobility leads to
      loss of body cell mass.

PMID- 8303748
TI  - Space-occupying cerebellar infarction. Clinical course and prognosis.
AB  - BACKGROUND AND PURPOSE: Because the timing and strategy of surgical intervention
      in massive cerebellar infarction remains controversial, we report our experience
      with the management of 52 such patients. METHODS: Case records, computed
      tomographic scans, surgical reports, and angiograms of 52 patients with space
      occupying cerebellar infarction defined by computed tomographic criteria were
      reevaluated with regard to clinical course, etiology, therapeutic management,
      mortality, and functional outcome. RESULTS: In most cases clinical deterioration
      started on the third day after stroke, and a comatose state was reached within 24
      hours. Sixteen patients were treated medically, and 30 by suboccipital
      craniectomy (22 plus ventriculostomy, 12 plus tonsillectomy). Ten patients
      primarily had ventriculostomy, which in 4 patients was supplemented by craniotomy
      because of continuing deterioration. Twenty-nine patients made a good recovery,
      15 remained disabled, and 8 died. Even comatose patients had a 38% chance of a
      good recovery with decompressive surgery. Age older than 60 years (P = .0043) and
      probably initial brain stem signs (P = .0816) and a late clinical stage (P =
      .0893) were linked with a fatal or disabling outcome. CONCLUSIONS: Decompressive
      surgery should be the treatment of choice for massive cerebellar infarction
      causing progressive brain stem signs or impairment of consciousness.

PMID- 8303749
TI  - Decreased cerebrovascular dilatory capacity in subjects with asymptomatic
      periventricular hyperintensities.
AB  - BACKGROUND AND PURPOSE: The clinical significance of the periventricular
      hyperintensity incidentally found on magnetic resonance images of the brain is
      questionable. We evaluated resting cerebral blood flow and cerebrovascular
      dilatory capacity of subjects with asymptomatic periventricular hyperintensities
      to study their cerebral hemodynamics. METHODS: Magnetic resonance imaging of the
      brain was performed in 28 asymptomatic subjects with cerebrovascular risk factors
      to determine the severity of periventricular hyperintensity. Mean gray matter
      flow was computed by a 133Xe-clearance technique in subjects at rest and after
      the administration of 1 g acetazolamide. Flow values were correlated with the
      scores for periventricular hyperintensity. RESULTS: Resting gray matter flow was
      not significantly correlated with the severity of periventricular hyperintensity
      for the whole brain (rs = -.364), whereas flow after acetazolamide loading (rs = 
      .783, P < .001) and the absolute value of increased flow (rs = -.567, P < .01)
      were significantly and negatively correlated with the severity of periventricular
      hyperintensity. CONCLUSIONS: A decrease in vasodilatory capacity and compensatory
      vasodilation occur in the cerebral cortex of subjects with asymptomatic
      periventricular lesions and maintain cerebral blood flow.

PMID- 8303750
TI  - Usefulness of an intravenous contrast medium in the characterization of high
      grade internal carotid stenosis with color Doppler-assisted duplex imaging.
AB  - BACKGROUND AND PURPOSE: The remaining limitations of ultrasonographic imaging in
      accurately quantifying internal carotid stenosis or diagnosing internal carotid
      occlusion may be overcome by enhancing the echogenicity of flowing arterial blood
      with contrast agents. This study assessed the usefulness of the intravenous
      (transpulmonary) contrast medium SH U 508 A in improving the characterization and
      quantification of severe internal carotid stenosis. METHODS: We examined 32
      patients (30 had vessels with a stenosis of greater than 70% luminal narrowing
      and 2 had vessel occlusions) using a 7.5-MHz linear-array transducer for color
      Doppler-assisted duplex imaging before and after injection of the contrast
      medium. RESULTS: The SH U 508 A-induced increase in carotid blood echogenicity
      began 11 +/- 2 (mean +/- SD) seconds after the start of the bolus injection,
      peaked at 21 +/- 2 dB, and showed a half-life of 75 seconds. Quantitative
      vascular measurements (cross-sectional luminal area reduction and plaque length,
      respectively) obtained before and after contrast application were highly
      correlated (r > .90). Visualization of the entire length of the intrastenotic
      residual flow lumen, however, was significantly improved by contrast enhancement
      (52% versus 83%, P = .01). CONCLUSIONS: This pilot study on patients with
      extracranial carotid artery disease suggested that ultrasonic contrast media may
      be most useful in improving the ultrasonography-based diagnosis of internal
      carotid occlusion.

PMID- 8303751
TI  - Noninvasive detection of intracranial vascular lesions by recording blood flow
      sounds.
AB  - BACKGROUND AND PURPOSE: Transorbital blood flow sound recordings have the
      potential to be used for noninvasive detection of cerebral aneurysms and
      arteriovenous malformations. We describe our system and experience in detecting
      intracranial cerebrovascular disease. METHODS: We investigated the noninvasive
      detection of intracranial vascular lesions by recording and analyzing the
      intracranial blood flow sounds. A new small transducer was placed on the
      unilateral eyelid to record the intracranial blood flow sounds, which were
      amplified and converted to digital data at a sampling frequency of 2000 Hz to
      provide a spectral analysis. RESULTS: No spectral peaks were recorded in 30
      healthy adults. Sharp peaks were recorded in 12 of 15 patients with unclipped
      aneurysms, and broad peaks were recorded in two patients with vasospasm after
      aneurysmal clipping and in all patients with severe intracranial internal carotid
      artery stenosis. CONCLUSIONS: This noninvasive technique has the potential to be
      very useful in the detection of intracranial cerebrovascular disease, including
      aneurysm and arterial stenosis, and could be used in mass screening examinations.

PMID- 8303752
TI  - Changes in blood flow velocity in the middle cerebral artery during nonpulsatile
      hypothermic cardiopulmonary bypass.
AB  - BACKGROUND AND PURPOSE: We evaluated the utility of blood flow velocity
      measurements by transcranial Doppler ultrasonography as a tool to indirectly
      measure cerebral perfusion during cardiopulmonary bypass. METHODS: We
      simultaneously measured blood flow velocity in the middle cerebral artery and
      physiological variables in 18 patients undergoing cardiac surgery under
      hypothermic cardiopulmonary bypass in which pH and PaCO2 were managed with the
      alpha-stat acid-base strategy. We expressed blood flow velocity as a relative
      value of control obtained under normothermia and normocarbia before bypass. We
      also developed an original index, modified cerebral metabolic rate for oxygen, to
      estimate cerebral metabolic rate for oxygen. RESULTS: Relative velocity was
      significantly (P < .01) reduced during stable aortic cross-clamp compared with
      before bypass and was significantly (P < .01) increased during rewarming compared
      with at aortic cross-clamp. Modified cerebral metabolic rate for oxygen
      significantly correlated with nasopharyngeal temperature during cooling, aortic
      cross-clamp, and rewarming (r = .756, P < .0001; r = .4, P < .01; r = .725, P <
      .0005, respectively). Calculated temperature coefficient for modified cerebral
      metabolic rate of oxygen was 2.7 +/- 1.4 (mean +/- SD, n = 10) during cooling.
      Only nasopharyngeal temperature and PaCO2 were significant determinants of
      relative velocity during aortic cross-clamp. CONCLUSIONS: We can monitor cerebral
      perfusion and metabolism by measurements of relative velocity and modified
      cerebral metabolic rate for oxygen during hypothermic cardiopulmonary bypass.

PMID- 8303753
TI  - Comparison of magnetic resonance volume flow rates, angiography, and carotid
      Dopplers. Preliminary results.
AB  - BACKGROUND AND PURPOSE: We compared the results of conventional angiography,
      carotid Doppler, and magnetic resonance angiography volume flow rates to
      determine the clinical utility of volume flow rate assessment of blood flow to
      the anterior circulation in patients with carotid occlusive disease. METHODS:
      From 11 symptomatic patients, a total of 22 extracranial carotid arteries were
      studied with all three techniques. The studies were independently read, and
      regression analysis was used to compare the measurements. RESULTS: Carotid
      Doppler measurements of the distal extracranial carotid arteries were
      proportional to the inverse of the extracranial carotid volume flow rate (r =
      .53, R2 = 29%, P < .01), volume flow rates were proportional to the inverse of
      measured percent stenosis on angiography (r = .84, R2 = 71%, P < .01), and
      Dopplers were proportional to angiography (r = .94, R2 = 90%, P < .01).
      Symptomatic Doppler systolic velocity was significantly higher (P < .002),
      symptomatic measured stenosis was significantly higher (P < .002), and
      symptomatic volume flow rate was significantly lower (P < .01) than their
      respective asymptomatic-side values. These preliminary observations, however, may
      well change once a large data set, especially one in which more patients with
      high-grade carotid stenosis are included, is studied. CONCLUSIONS: Assessment of
      carotid volume flow rates by magnetic resonance angiography quantifies flow
      reduction secondary to atherosclerotic occlusive disease. The easily obtained
      flow data add both documentation of arterial flow characteristics related to
      internal carotid stenosis and information regarding the adequacy of collateral
      pathways.

PMID- 8303754
TI  - Safety study of tirilazad mesylate in patients with acute ischemic stroke
      (STIPAS).
AB  - BACKGROUND AND PURPOSE: Tirilazad mesylate, a 21-amino-steroid, is a potent
      membrane lipid peroxidation inhibitor and free radical scavenger that has shown
      promise in animal models of focal cerebral ischemia. Safety in patients with
      acute ischemic stroke has not yet been established. METHODS: The study comprised
      a randomized (three drugs to one vehicle), vehicle-controlled, double-blind,
      sequential dose-escalation trial at five centers. Treatment was begun within 12
      hours of stroke onset and was continued intravenously for 3 days. RESULTS: One
      hundred eleven patients (mean +/- SD age, 66 +/- 13 years; 56% male) were
      enrolled in three successive dosage tiers: 36 at 0.6 mg/kg per day, 35 at 2.0
      mg/kg per day, and 40 at 6.0 mg/kg per day. Median time from stroke onset to
      treatment was 8.5 (range, 3 to 12) hours and was not significantly different
      among the groups. Tirilazad was well tolerated at all three doses, except for
      mild-to-moderate injection site irritation that occurred in both the tirilazad-
      and vehicle-treated groups. No significant differences in measures of either
      cardiac or hepatic toxicity were observed in this small sample. Imbalances in
      baseline medical and neurological condition made comparisons of outcome
      difficult. Although no evidence suggestive of tirilazad efficacy was apparent in
      this study, the trial was not designed to test for differences in outcome.
      CONCLUSIONS: These observations suggest that intravenous tirilazad at doses of up
      to 6.0 mg/kg per day for 3 days is well tolerated in this population of
      predominantly elderly stroke patients. Larger studies with earlier treatment will
      be needed to demonstrate efficacy.

PMID- 8303755
TI  - Gamma irradiation inhibits neointimal hyperplasia in rats after arterial injury.
AB  - BACKGROUND AND PURPOSE: Restenosis complicates a significant proportion of
      endovascular and open vascular procedures such as carotid endarterectomy. In
      contrast to the primary atheroma, restenosis is characterized by intimal
      hyperplasia of vascular smooth muscle cells. We hypothesized that gamma radiation
      would reduce restenosis by limiting intimal hyperplasia after arterial injury.
      METHODS: To demonstrate the effect of gamma radiation on smooth muscle
      hyperplasia in vivo, a standardized bilateral carotid balloon catheter arterial
      injury was produced in 37 rats. A single dose of 750, 1500, or 2250 cGy (1cGy = 1
      rad) gamma radiation was delivered to the right carotid artery at either 1 or 2
      days after injury; the shielded contralateral carotid artery served as matched
      control. At 21 days after injury, vessels were perfusion-fixed in situ, and cross
      sectional area of neointima was determined from axial sections using image
      analysis. RESULTS: Marked reductions in neointimal cross-sectional area were
      demonstrated in vessels subjected to 1500- and 2250-cGy radiation at both 1 and 2
      days after injury. A less prominent effect was noted for 750 cGy, reaching
      statistical significance only at 2 days after injury. By two-way ANOVA, radiation
      dose (P = .0002), timing of radiation delivery (P = .003), and an interaction
      between timing and dose (P = .0278) were significantly associated with reduction
      in neointimal cross-sectional area. At 1500 cGy, delivery of radiation 1 day
      after injury inhibited neointimal hyperplasia more prominently than the same dose
      2 days after injury; a dose-response relation was evident at 1 day. CONCLUSIONS:
      Radiation may be an important adjunctive therapy for reducing the incidence of
      restenosis after angioplasty or endarterectomy.

PMID- 8303756
TI  - Tissue-type plasminogen activator improves neurological functions in a rat model
      of thromboembolic stroke.
AB  - BACKGROUND AND PURPOSE: The capacity of an intravenous infusion of double
      stranded tissue-type plasminogen activator to salvage neurological functions in a
      rat model of thromboembolic stroke was studied. METHODS: The model of
      thromboembolic stroke was induced by the intracarotid injection of 2-hour-old
      homologous blood clots to rats. Neurological functions were scored on a 5-point
      scale 48 hours after the injection of the clots. Infarction size was determined
      by triphenyltetrazolium chloride staining, and cerebral hemorrhage was examined
      macroscopically. RESULTS: Intravenous infusion of tissue-type plasminogen
      activator (1 or 5 x 10(5) IU/kg) within 3 hours after embolization significantly
      improved neurological functions (P < .01) and reduced infarction size (P < .05).
      Tissue-type plasminogen activator treatment 6 hours after embolization failed to
      attenuate the neurological status score. Treatment with tissue-type plasminogen
      activator did not increase the incidence of intracerebral hemorrhage and was not
      associated with a systemic fibrinolytic state. In comparison with tissue-type
      plasminogen activator treatment, although urokinase treatment (5 x 10(5) IU/kg)
      improved neurological functions, it was associated with a systemic fibrinolytic
      state and a tendency to increase the incidence of intracerebral hemorrhage.
      CONCLUSIONS: These findings in this model suggest that tissue-type plasminogen
      activator should be given early after the onset of ischemic symptoms to
      effectively prevent or limit pathological infarction and improve neurological
      functions without an increase in the incidence of cerebral hemorrhage.

PMID- 8303757
TI  - Delayed protection by MK-801 and tetrodotoxin in a rat organotypic hippocampal
      culture model of ischemia.
AB  - BACKGROUND AND PURPOSE: The hippocampus demonstrates a regional pattern of
      vulnerability to ischemic injury that depends on its characteristic
      differentiation and intrinsic connections. We now describe a model of ischemic
      injury using organotypic hippocampal culture, which preserves the anatomic
      differentiation of the hippocampus in long-term tissue culture. METHODS: Ischemic
      conditions were modeled by metabolic inhibition. Cultures were briefly exposed to
      potassium cyanide to block oxidative phosphorylation and 2-deoxyglucose to block
      glycolysis. The fluorescent dye propidium iodide was used to observe membrane
      damage in living cultures during recovery. RESULTS: 2-Deoxyglucose/potassium
      cyanide incubation resulted in dose-dependent, regionally selective neuronal
      injury in CA1 and the dentate hilus, which began slowly after 2 to 6 hours of
      recovery. Subsequent histological examination of cultures after 1 to 7 days of
      recovery demonstrated neuronal pyknosis that was correlated with the early,
      direct observation of membrane damage with propidium. Both propidium staining and
      histological degeneration were prevented by the noncompetitive N-methyl-D
      aspartate (NMDA) receptor antagonist MK-801 when administered 30 minutes after
      the end of the exposure to 2-deoxyglucose and potassium cyanide. Tetrodotoxin,
      which blocks voltage-dependent sodium channels, had protective effects that were
      greatest during the period of 2-deoxyglucose and potassium cyanide incubation but
      also produced protection against the mildest conditions of metabolic inhibition
      when administered after 30 minutes of recovery. CONCLUSIONS: This in vitro model
      reproduced elements of the time course, regional vulnerability, and pharmacologic
      sensitivities of in vivo ischemic hippocampal injury. Inhibition of metabolism in
      organotypic culture provides a rapid, easily controlled injury and reproduces the
      in vitro pattern of hippocampal regional vulnerability to ischemia. It is the
      first in vitro model of ischemia to exhibit complete protection by delayed
      administration of an NMDA receptor antagonist during recovery from a brief
      insult. The protective effects of tetrodotoxin suggest that an early period of
      sodium entry into cells during and after ATP depletion may be responsible for the
      more prolonged period of toxic NMDA receptor activation.

PMID- 8303758
TI  - Calcium/calmodulin-dependent protein kinase II activity in focal ischemia with
      reperfusion in rats.
AB  - BACKGROUND AND PURPOSE: Evidence linking changes in calcium/calmodulin-dependent
      protein kinase II activity with ischemic cell death has been reported in animal
      models of global ischemia. The purpose of this study was to delineate the course
      of these changes after focal ischemia and to clarify the relation of changes in
      activity of calcium/calmodulin-dependent protein kinase II to the process of
      ischemic cell death. METHODS: Change in calcium/calmodulin-dependent protein
      kinase II activity was evaluated in a rat model of focal ischemia after 5
      minutes, 30 minutes, and 1 hour of tandem middle cerebral artery and common
      carotid artery occlusion both with and without reperfusion. RESULTS:
      Calcium/calmodulin-dependent protein kinase II activity was significantly
      decreased after all three durations of ischemia followed by immediate
      decapitation compared with sham-operated animals, in both ischemic core and
      border-zone regions (P < .05 for all groups). Depression of activity occurred in
      a regionally graded fashion, with the most severe decrease in infarct core and
      progressively smaller decreases in samples moving out from the center,
      corresponding to the severity of histological injury later detected in infarct
      core and border-zone regions. There were only minor differences between the three
      durations of ischemia in the degree of enzyme depression noted in the more
      peripheral regions, indicating that the initial decrease in calcium/calmodulin
      dependent protein kinase II activity is an early, sensitive marker for an
      ischemic insult. After reperfusion, the differences between the 5-minute group
      and longer periods of ischemia widened because of an increase toward baseline in
      the 5-minute group and a trend toward further decrease in the 30- and 60-minute
      groups. CONCLUSIONS: The extreme sensitivity of calcium/calmodulin-dependent
      protein kinase II to focal ischemia and the parallel temporal and regional
      changes in its activity to those of more delayed cell injury point to a potential
      role for this enzyme in the process of excitotoxic injury.

PMID- 8303759
TI  - Effects of clentiazem on cerebral ischemia induced by carotid artery occlusion in
      stroke-prone spontaneously hypertensive rats.
AB  - BACKGROUND AND PURPOSE: We examined metabolic and functional changes when
      forebrain ischemia was induced in stroke-prone spontaneously hypertensive rats by
      bilateral carotid artery occlusion. In addition, the protective effect of
      clentiazem was evaluated in this model. METHODS: Rats were anesthetized with
      urethane. Cerebral blood flow was measured with a laser Doppler flowmeter.
      Cerebral high-energy phosphates and intracellular pH were measured by phosphorus
      magnetic resonance spectroscopy. Electroencephalographic activity was evaluated
      as the summation of its amplitude. These parameters were monitored during a 30
      minute period of ischemia and recirculation. Clentiazem was given orally as
      pretreatment (10 mg/kg twice a day for 3.5 days). RESULTS: Bilateral carotid
      occlusion caused a decrease in cerebral blood flow to approximately 5% of the
      preischemic level and the disappearance of electroencephalographic activity.
      Occlusion also caused a decrease in ATP and phosphocreatine (to 48.7 +/- 4.3% and
      23.7 +/- 2.2% of preischemic levels, respectively) as well as intracellular pH
      (from 7.3 +/- 0.1 to 6.0 +/- 0.1). During recirculation the reversal of these
      changes was variable: high-energy phosphates were partially restored, but
      electroencephalographic activity and intracellular pH showed little improvement.
      Hypoperfusion (55.7 +/- 11.5% of the preischemic flow) developed after reactive
      hyperemia. Pretreatment with clentiazem lessened the decrease in cerebral blood
      flow (control, 4.8 +/- 1.4%; clentiazem, 14.1 +/- 4.1% of the preischemic level;
      P < .05) and prevented the disappearance of electroencephalographic activity in
      some rats during ischemia. Clentiazem also prevented postischemic hypoperfusion
      and accelerated the restoration of high-energy phosphates, intracellular pH, and
      electroencephalographic activity during recirculation. CONCLUSIONS: Carotid
      artery occlusion induced stable forebrain ischemia in stroke-prone spontaneously
      hypertensive rats. Clentiazem improved the metabolic and functional disturbances
      that occurred in this ischemic model, and its beneficial effect appeared to be
      due mainly to the relative preservation of cerebral blood flow during carotid
      occlusion.

PMID- 8303760
TI  - The effect of ritanserin, a 5-HT2 receptor antagonist, on ischemic cerebral blood
      flow and infarct volume in rat middle cerebral artery occlusion.
AB  - BACKGROUND AND PURPOSE: In a previous study from our laboratory, ritanserin, a
      specific 5-HT2 serotonin receptor antagonist, reduced ischemic damage in the
      setting of transient global ischemia. In this study, we examined the effect of
      ritanserin on ischemic cerebral blood flow, systemic blood pressure, and infarct
      volume in the model of permanent focal ischemia with brain temperature controlled
      at 35.0 degrees C to 36.0 degrees C. METHODS: Thirty-seven male Sprague-Dawley
      rats were used. The right middle cerebral artery was permanently occluded.
      Ritanserin (8 mg/kg) or vehicle was continuously administered intravenously for
      90 minutes starting 10 minutes after middle cerebral artery occlusion. Cerebral
      blood flow was monitored by laser Doppler flowmetry in the ischemic cortex before
      and for 2 hours after arterial occlusion. Brains were perfusion-fixed 3 days
      later, and infarct volumes were measured. RESULTS: Mean arterial blood pressure
      was not affected by treatment. In the vehicle and ritanserin groups, mean
      ischemic cerebral blood flow (percent of preischemic values) was 34.6 +/- 14.7%
      (mean +/- SD) and 26.6 +/- 15.0%, respectively. Hemispheric infarct volumes were
      119.3 +/- 49.4 mm3 and 136.6 +/- 49.6 mm3, respectively. No significant
      differences were recognized. CONCLUSIONS: Intravenous administration of
      ritanserin did not affect mean arterial blood pressure or cerebral blood flow in
      the ischemic region during the acute phase of ischemia. No protective effect of
      ritanserin was apparent in the setting of permanent focal ischemia when treatment
      was begun shortly after the onset of ischemia.

PMID- 8303761
TI  - Efficacious experimental stroke treatment with high-dose methylprednisolone.
AB  - BACKGROUND AND PURPOSE: Recent studies reveal success in treating spinal cord
      trauma with early, high-dose methylprednisolone. As in spinal cord research,
      failure to find therapeutic effects with steroids in studies of acute stroke
      treatment may reflect institution of treatment too late and at too low dosage. We
      presently test the efficacy of stroke treatment with methylprednisolone
      administered early and at high doses using a cat temporary middle cerebral artery
      occlusion model. METHODS: We occluded the middle cerebral artery for 4 hours in
      24 pentobarbital-anesthetized cats. To enhance the probability of brain injury,
      we maintained the cats' serum glucose concentrations at high levels both during
      occlusion and for 6 hours afterward. Using a blinded, randomized study design, we
      treated 12 cats with methylprednisolone (30 mg/kg IV infused over 15 minutes
      starting 30 minutes after occlusion followed by 5.4 mg.kg-1.h-1 IV for the next
      23 hours) and 12 control cats with vehicle. During and for 8 hours after
      occlusion, we monitored cerebral blood flow, brain and rectal temperatures, and
      multiple cardiovascular and blood compositional parameters. We assessed brain
      pathological outcome after animal survival for 4 days or after acute death from
      hemispheric edema. RESULTS: Experimental and control animals showed similar early
      mortality rates (treated, 3/12; controls, 4/12). However, surviving
      methylprednisolone-treated cats (n = 9) showed a mean infarct size more than six
      times smaller than in the control animals (n = 8) (mean +/- SEM, 2.4 +/- 0.7%
      versus 15.6 +/- 6.2% of the ischemic territory, respectively; P < .05). The
      methylprednisolone-treated animals also showed less marked reduction in cerebral
      blood flow during ischemia than did the controls (mean +/- SEM, 58 +/- 5% versus
      74 +/- 4%; P < .005). CONCLUSIONS: Administering methylprednisolone at high doses
      early after onset of ischemia significantly reduces tissue injury in cats that
      survive 4 days of temporary middle cerebral artery occlusion. This improvement in
      outcome occurs in the setting of significant increases in ischemic cerebral blood
      flow. However, methylprednisolone treatment did not reduce hemispheric edema in
      animals that died early after temporary middle cerebral artery occlusion.

PMID- 8303762
TI  - Diffusion nuclear magnetic resonance imaging in experimental stroke. Correlation
      with cerebral metabolites.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted nuclear magnetic resonance imaging has
      been shown to detect early ischemia-related alterations in experimental stroke.
      This raises the question of whether the observed increase in signal intensity is
      correlated with changes in cerebral metabolism. After middle cerebral artery
      occlusion, nuclear magnetic resonance diffusion images were recorded and compared
      with the regional concentration of cerebral metabolites and with histology of
      identical planes. METHODS: Seven anesthetized Fischer rats were subjected to
      permanent occlusion of the middle cerebral artery. T1, T2, and diffusion images
      (b factors ranging from 0 to 1500 s/mm2) were measured in three to five planes
      after 7 hours. Thereafter, brains were frozen in situ for histology and
      quantitative bioluminescence imaging of ATP, glucose, lactate, and for
      fluorescence imaging of tissue pH. RESULTS: Seven hours after middle cerebral
      artery occlusion, the apparent diffusion coefficient was reduced from 615 +/- 97
      x 10(-6).mm2.s-1 (contralateral brain) to 359 +/- 42 x 10(-6).mm2.s-1 (ischemic
      brain; mean +/- SD, P < .01). A precise topical coincidence was demonstrated
      between changes in nuclear magnetic resonance diffusion images, pattern of
      histological damage, ATP-depleted areas, and local tissue acidosis, the lesion
      area amounting to between 24.1% and 27.6% of the hemisphere at the level of the
      caudate-putamen. The area of elevated brain lactate clearly exceeded the acidic
      core of the infarct and included the slightly alkaline border zone. CONCLUSIONS:
      The data demonstrate that after 7-hour middle cerebral artery occlusion, the
      reduction of the apparent diffusion coefficient in nuclear magnetic resonance
      diffusion images reflects precisely the region of histological injury, breakdown
      of energy metabolism, and tissue acidosis.

PMID- 8303763
TI  - Variations in the anatomy of the rabbit cervical carotid artery.
AB  - BACKGROUND AND PURPOSE: A model for cerebral ischemia that requires injection of
      emboli into the internal carotid artery of the rabbit is commonly used. However,
      in our experience we have found the anatomy of the cervical carotid to be highly
      variable. If not appreciated, this may result in unexpectedly high variability in
      the severity of ischemic injury. We undertook this experimental protocol to
      determine whether it was possible to characterize the anatomy of the rabbit
      cervical carotid artery. METHODS: We examined and recorded the architecture of
      the cervical carotid arteries of 105 consecutive rabbits involved in experimental
      protocols to evaluate the role of tissue-type plasminogen activator during
      embolic stroke. RESULTS: Two basic patterns of origin of the internal carotid
      artery were identified: lateral origin, classified as type I, and dorsomedial
      origin, classified as type II. In addition, there were three subsequent
      variations in the origin and morphology of the occipital artery in relation to
      the internal carotid artery: origin from the external carotid artery (subtype A);
      origin proximal on the internal carotid artery (subtype B); and origin distal on
      the internal carotid artery (subtype C). CONCLUSIONS: The classification of the
      anatomy of the cervical carotid artery of the rabbit into these easily recognized
      types will assist those attempting to use this embolization model. Failure to
      recognize the origin of the occipital artery from the internal carotid artery can
      result in the misdirection of embolic material into the occipital artery and
      significantly reduce the effectiveness of this stroke model.

PMID- 8303764
TI  - Draining vein pressure increases and hemorrhage in patients with arteriovenous
      malformation.
AB  - BACKGROUND: Recent radiological studies have shown that arteriovenous
      malformations with impaired venous drainage may be susceptible to hemorrhage. To
      evaluate this hypothesis using a hemodynamic approach, we measured intravascular
      pressure during surgery in three patients with arteriovenous malformation.
      SUMMARY OF REPORT: In three patients we measured intravascular pressures in the
      draining venous system and the feeding arteries simultaneously before removal of
      arteriovenous malformations with marked segmental stenotic or occlusive draining
      veins and evidence of hemorrhage. The draining vein pressures at prestenotic (or
      preocclusive) sites in the three patients were 38, 25, and 40 mm Hg,
      respectively, all significantly above the normal cortical venous pressure,
      whereas pressure measurements in poststenotic sites and the sagittal sinus
      pressure in the venous drainage system approached normal values. The feeding
      artery pressures in the patients were lower than normal cortical artery pressure
      because of the arteriovenous shunt. CONCLUSIONS: Intraoperative vascular pressure
      measurements support the hypothesis that arteriovenous malformations with
      impaired venous drainage may be associated with a local increase in venous
      pressure and thus may be susceptible to hemorrhage.

PMID- 8303765
TI  - Congenital deficiency of factor VII in subarachnoid hemorrhage.
AB  - BACKGROUND: Factor VII is essential for coagulation activation by the extrinsic
      pathway. Hemorrhages of the central nervous system in patients with congenital
      factor VII deficiency seem to have a higher incidence compared with other
      congenital coagulopathies. The purpose of this paper is to report two rare cases
      of subarachnoid hemorrhage and factor VII deficiency. CASE DESCRIPTION: Two cases
      of women affected by a congenital deficiency of factor VII and subarachnoid
      hemorrhage are reported. Diagnosis was obtained by cerebral computer tomography;
      cerebral pan-angiography was normal. Complete coagulation studies were performed
      showing prothrombin time prolongation and factor VII deficiency. In one patient,
      family studies revealed the existence of a similar coagulation disorder.
      CONCLUSIONS: We suggest routine coagulation studies in all patients with
      subarachnoid hemorrhage. Determination of factor VII activity might be performed
      in patients with normal activated partial thromboplastin time and prolonged
      prothrombin time.

PMID- 8303766
TI  - Cerebral ischemic attack caused by postprandial hypotension.
AB  - BACKGROUND: Food ingestion sometimes induces systemic hypotension (postprandial
      hypotension). Although the possibility of stroke occurring postprandially has
      been suggested, no cases have been reported until now. CASE DESCRIPTION: A 78
      year-old man experienced repeated transient ischemic attacks after almost every
      ingestion of food and showed orthostatic and postprandial hypotension. An
      angiogram revealed occlusion of his left carotid artery and stenosis of his right
      middle cerebral artery. CONCLUSIONS: Postprandial as well as orthostatic
      hypotension can be a risk factor for stroke in patients with severe occlusive
      cerebrovascular disease.

PMID- 8303767
TI  - Motor recovery after early brain damage. A case of brain plasticity.
AB  - BACKGROUND: Motor recovery is remarkable when the brain is damaged early in life.
      We describe a case of early damage to the right hemisphere with remarkable
      reorganization and plastic functional changes, studied by computed neuroimaging.
      CASE DESCRIPTION: A 31-year-old man had a left-sided hemiplegia at the age of 12,
      followed by good motor recovery despite a large right cortical-subcortical
      lesion. Single-photon emission computed tomography with motor activation study
      showed cerebral blood flow increase in the left premotor and sensorimotor
      cortices irrespective of the hand he was moving, without flow changes in the
      right hemisphere. CONCLUSIONS: A remarkable reorganization and plastic brain
      functional changes occurred in a patient after early diffuse damage of the right
      hemisphere. The study points to a potential role of ipsilateral cortical efferent
      pathways in subserving hand movements after early cerebral damage.

PMID- 8303768
TI  - Malignant brain stem hyperthermia caused by brain stem hemorrhage.
AB  - BACKGROUND: We report two cases of brain stem hemorrhage characterized by severe
      hyperthermia, rhabdomyolysis, acute renal failure, and a rapidly fatal course.
      METHODS: A 55-year-old man and a 65-year-old man were admitted with coma
      producing brain stem hemorrhage accompanied by hyperthermia. Both underwent
      ventricular drainage. RESULTS: Within 1 day of onset, both patients developed
      hyperthermia of over 41 degrees C, increased serum creatine phosphokinase (CPK)
      level indicating rhabdomyolysis, and acute renal failure. One patient died on the
      second day and the other on the third day after onset despite supportive
      treatment. CONCLUSIONS: These cases of brain stem hemorrhage with fulminant
      hyperthermia should be distinguished from those with simple hyperthermia. They
      may represent a kind of malignant hyperthermia, in which case dantrolene sodium
      might be beneficial. Monitoring serum CPK levels would be of help in making the
      diagnosis early in the course.

PMID- 8303769
TI  - Apolipoprotein E polymorphism and ischemic cerebrovascular disease.

PMID- 8303770
TI  - Handling of anger and ischemic stroke in women.

PMID- 8303771
TI  - Controversies in stroke: past and present.

PMID- 8303772
TI  - Pharmacologically induced hypothermia for cerebral protection in humans.

PMID- 8303773
TI  - Hyperglycemia in the acute phase of stroke and stress response.

PMID- 8303774
TI  - Nailfold capillary microscopy in lacunar infarction.

PMID- 8303775
TI  - Cervicocephalic arterial dissections related to skiing.

PMID- 8303776
TI  - Ultrastructural study of macrophages of the rat thymus after cyclosporin
      treatment.
AB  - Young adult male Wistar rats were given 30 mg per kg of cyclosporin (CS) for 21
      consecutive days. After CS treatment thymic medulla virtually disappears and the
      thymus is almost entirely composed of cortical tissue. Macrophages are scattered
      throughout the thymic cortex. These cells are very large, rounded, with
      inconspicuous prolongations and euchromatic nucleus with prominent nucleoli.
      These cells are loaded with lipid bodies and vacuolar cytoplasmic inclusions of
      different size and diverse content, but very rarely contain phagocytosed
      lymphocyte remnants. The cytoplasm between inclusions has very active aspect with
      abundance of polyribosomes, granular endoplasmic reticulum and vesicles. Mitoses
      of lymphocytes in the vicinity of macrophages are frequently seen. We discuss the
      morphological similarity between cortical macrophages of CS-treated thymus and
      macrophages of cortico-medullary zone (CMZ) of the normal rat thymus, as well as
      functional significance of described morphological characteristics of this type
      of thymic macrophages, which probably reflect the metabolism of arachidonic acid.

PMID- 8303777
TI  - IL-1 mRNA expression detected by in situ hybridization and polymerase chain
      reaction in human thymus and thymoma. Correlation with late T-cell maturation in
      normal versus neoplastic thymus.
AB  - Interleukin-1 has long been suggested to participate in the development of T
      cells in the thymus. To determine whether IL-1 was produced in the human thymus,
      we used the technique of in situ hybridization and PCR amplification of mRNA.
      High levels of IL-1 mRNA were detected in cells at the cortico-medullary border,
      which separates immature from mature T-cells, suggesting a role for IL-1 in a
      late stage in T-cell maturation. IL-1 transcripts were detectable by a single
      step PCR reaction in these samples. We examined a series thymomas (human thymic
      epithelial tumors) that induce partial T-cell maturation: In this group of
      thymomas T-cells develop to the cortical stage but not beyond. We failed to
      detect high levels of IL-1 mRNA expression in these tumors by in-situ
      hybridization, IL-1 mRNA was detected only in one of these samples by a single
      step PCR amplification. However, all of the samples were positive, when analyzed
      with a more sensitive, two step amplification of IL-1 mRNA by the use of nested
      primers. These results are consistent with the hypothesis that higher level of IL
      1 expression is either the consequence of, or required for late T-cell
      maturation.

PMID- 8303779
TI  - [When medicine conceives its proper ingenuity... Interview by Robert Henry].

PMID- 8303778
TI  - Membrane translocation and relationship with MHC class I of a human thymic
      neurophysin-like protein.
AB  - Thymic epithelial and nurse cells (TEC/TNC) synthesize an oxytocin (OT)-like
      peptide in association with a neurophysin (NP)-related protein in a way similar
      to in the hypothalamo-neurohypophysial (NHP) system. The central T-cell tolerance
      of the NHP neuroendocrine functions have been proposed to be mediated through
      these thymic NHP-related peptides due to their close homology with the NHP
      neurohormones OT and vasopressin (VP). In order to investigate their putative
      presentation by proteins of the major histocompatibility complex (MHC), human
      thymic membranes were purified and passed through an immunoaffinity column using
      mAb B9.12 directed to the monomorphic determinant of human MHC class I proteins.
      This methodology provided the following observations: (1) a NP-like protein is
      translocated in human thymic membranes and is retained by B9.12 on the column;
      (2) the MW of this NP-like material (50-55 kD) is quite different from the MW of
      hypothalamic NP proteins (10 kD), and (3) this thymic NP-like protein could be
      identified on Western blots with mAb B9.12. The precise extent of this
      relationship between the thymic NP-like protein and the Ig/MHC superfamily is
      actually investigated through the characterization of the genetic mechanisms
      responsible for the thymic expression of NHP-related peptides. Given the
      physiological importance of OT and of its binding to NP for transport along the
      axonal processes of the NHP tract, we postulate that, somewhat analogously, the
      thymic NP-/MHC class I-related protein could be involved in the presentation of
      the OT-like peptide to immature T-cells.

PMID- 8303780
TI  - [Muscular weakness in a young woman].

PMID- 8303781
TI  - [1992 update on the periodic medical examination. 4. Prophylaxis of gonococcal
      and Chlamydia ophthalmia in the newborn. Canadian study group on the periodic
      medical examination].

PMID- 8303782
TI  - [Research in psychiatry].
AB  - The department of psychiatry of the Universite de Montreal has now organized a
      well structured research network in the area of child, adult and forensic
      psychiatry. The authors summarize the scientific approach according to research
      in these different sectors and believe that, although research in psychiatry now
      tends to promote diagnostic and treatment methods based more and more on neuro
      sciences, it does not neglect the contribution of psychosocial and clinical
      aspects without which the human dimensions of mental illness and the objective of
      improvement of care to patients would be rapidly forgotten on behalf of
      disembodied research projects completely deprived of the relation with patients.

PMID- 8303784
TI  - [Hyperactivity in children: a valid diagnosis?].
AB  - Research has documented differences between hyperactive and normal children.
      However, to be valid, a diagnostic entity must differ in etiology, course,
      characteristics, or treatment response from other behavior problems as well as
      from normality. In order to demonstrate the validity of this syndrome, the
      research has followed three lines: the search for a biological marker, the study
      of symptoms and the evaluation of the suspected cognitives deficits. No final
      answers have been obtained yet but understanding of this clinical entity is still
      progressing.

PMID- 8303783
TI  - [Heterogeneity of cognitive profiles in dementias of the Alzheimer type:
      theoretical aspects and clinical consequences].
AB  - Presently, Alzheimer's disease can only be diagnosed with the coexistence of
      clinical symptoms and the presence of neuropathological alterations. Thus, in the
      absence of pre mortem biological markers, cognitive deficits form the starting
      point and the basis of inclusion criteria on which the clinician relies in order
      to make a putative diagnose of dementia of the Alzheimer type (DTA). Cognitive
      deficits should thus be accurately described through neuropsychological testing
      since it is essential to identify the cognitive deterioration patterns of the
      patients--in terms of selective impairment of cognitive functions--as well as the
      evolution of these patterns. Regarding this issue, the classical teaching of the
      Geneva school has proposed a homogeneous deterioration of the aphasic
      apraxicagnosic syndrome into four stages. However, recent work does not support
      this hypothesis. On the contrary, these studies tend to show the presence of
      heterogeneity in neuropsychological manifestations of the disease. The aim of the
      present paper is to provide a critical review of this topic through a brief
      survey of the classical work and research that have recently been conducted. An
      analysis of the possible candidates responsible for the existence of this
      heterogeneity of cognitive profiles is presented. Finally, theoretical
      implications and clinical repercussions are discussed.

PMID- 8303785
TI  - [Pathologies of the musculo-skeletal system in musicians].
AB  - Musculoskeletal problems are very frequent amongst musicians. The most frequent
      ones are tendinitis, professional cramps and dystonias, thoracic outlet syndrome,
      carpal tunnel syndrome, overuse syndrome and back pain. Preventive measures
      should included information to students about potential problems, body awareness,
      good physical condition, proper technique and early management of arising
      problems. In many cases, musicians consult only at an advance stage of their
      disease and a prolonged rest of the instrument is then mandatory but not easily
      accepted.

PMID- 8303786
TI  - [Oncology at the Hotel-Dieu in Montreal].
AB  - A review of various historical events in oncology at l'Hotel-Dieu de Montreal is
      presented as well as a description of the services offered and the structural
      organization of the oncology center. The surgical and medical oncology
      subspecialties are very active in clinical research. Their contribution to
      various protocols is noted and a highlight of their conclusions is given. The
      research unit in epidemiology has expertise in the nutritional evaluation of
      patients with cancer. They have also published two atlas on the mortality and
      incidence of cancer by regions in the Province of Quebec. The hospital has also a
      molecular pathology laboratory which helps physicians in pursuing the diagnosis
      and to understand the biology of cancers.

PMID- 8303787
TI  - [Chemoprevention of lung cancer].
AB  - Chemoprevention, or pharmacological intervention in healthy individuals at risk
      of developing cancer, is attracting attention as a potential tool in cancer
      prevention. Lung cancer, with its high incidence and poor prognosis, is a
      particularly interesting disease for these studies. The retinoids are a promising
      group of chemopreventive agents, since they are involved in growth control and
      are a necessary cofactor for proper activity of a protein receptor which we have
      shown to be a lung cancer suppressor. Nevertheless, the toxic side effects of
      retinoids at pharmacological dose present difficulties and current studies are
      aimed at determining the efficacy of various forms of retinoids and
      chemoprevention protocols in the target populations.

PMID- 8303788
TI  - [Profile of Chlamydia test utilization by the physicians of Laval].
AB  - Before recommending systematic screening for Chlamydia trachomatis in young
      sexually-active women in its population, the Laval Community Health Department
      set out to document current practices in chlamydia testing. The objective of the
      study was to determine for whom these tests were prescribed, by whom and why.
      Data were obtained from a representative sample of 413 medical records. The
      greatest proportion of tests were prescribed for young women between the ages of
      15-24 years. More than 85% of the tests were ordered by general practitioners,
      most of whom practiced in both hospital setting and private clinics. More than
      half of the tests were administered to obtain a diagnosis; approximately 42% were
      done for screening purposes. The study revealed a failure to document the sexual
      history of patients. It was estimated that between 30 and 40% of Chlamydia tests
      were not justified in being prescribed (according to the recommendations in the
      literature). It is possible that the criteria in the medical literature are too
      complex for use in everyday practice. The authors recommend the creation of
      specific tools adapted to physicians' needs, and the development of a screening
      program based on a systematic, step-by-step approach to determine whether or not
      a test is warranted.

PMID- 8303789
TI  - [Renal transplantations: current reality and future challenges].
AB  - Kidney transplantation is a well recognized form of treatment for end-stage renal
      failure patients. Transplanted patients can hope for a prolonged and productive
      life. Many factors are responsible for the improvement of kidney transplantation
      over the last years. Despite its progress and success, many limitations still
      exist: shortage of kidney, humoral hypersensitivity or recipients, side effects
      of immunosuppressive medication and chronic rejection. Will the induction of
      specific tolerance to xenograft, with the help of transgenic biology, be the
      solution of tomorrow?

PMID- 8303790
TI  - [New treatment strategies in coronary disease].
AB  - The mortality associated with coronary atherosclerosis has decreased by 30% to
      40% in the last few decades. This reduction has followed major pharmacological
      and biotechnological advances and can possibly be attributed to better management
      of risk factors for coronary atherosclerosis and to more effective therapy of its
      late manifestations. Nevertheless, the coronary artery disease remains a major
      public health problem. It is responsible for 40% to 45% of deaths in our
      population and, although it becomes manifest later than previously, its incidence
      and prevalence may not have declined significantly. Recent studies suggest that
      progression of coronary atherosclerosis can be delayed, that regression can also
      occur, and that this can lead to a reduction in morbidity and mortality. Several
      types of interventions have been performed in these studies. Some of them such as
      a drastic modification in lifestyle, the administration of one or several
      hypocholesterolemic agents or partial ileal bypass have achieved these results by
      markedly lowering LDL or raising HDL cholesterol. Other manipulations of plasma
      lipoproteins are also possible, such as the administration of specific protein or
      enzyme inhibitors, anti-oxidants and omega-3 fatty acids. Calcium antagonists and
      possibly angiotensin converting-enzyme inhibitors slow the progression of early
      coronary lesions and prevent the appearance of new lesions. These interventions,
      in addition to influencing the size of the atherosclerotic plaque, can have other
      important effects. They can contribute to the preservation of integrity and
      function of endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8303791
TI  - [The treatment of Cushing's disease].
AB  - The differential diagnosis of Cushing's disease remains difficult to establish.
      The selective transsphenoidal adenomectomy is the initial treatment of choice. In
      a group of 65 patients, 50 (77%) initially responded to surgery with correction
      of their hypercortisolism. Forty-three out of 51 (84%) patients with small
      pituitary tumors responded favourably to surgery, but recurrency occurred in 10%
      of the cases. Medical treatment with steroids inhibitors or antagonists is only
      an adjuvant treatment. In case of surgery failure or recurrency, bilateral
      adrenalectomy is usually performed. Conventional radiotherapy may be used after
      surgery in presence of macroadenomas or invasive adenomas. Correction of the
      hypercortisolism, after a second surgery, was achieved in 50% of the cases and
      was always associated with a panhypopituitarism.

PMID- 8303793
TI  - Familial subarachnoid haemorrhage.
AB  - Over the nineteen years 1974 to 1992 twenty-four families have been identified in
      whom more than one member have had a subarachnoid haemorrhage, usually due to
      rupture of an intracranial aneurysm. These cases usually occurred at an age
      younger than average, and multiple aneurysms were commonly found on
      investigation. This series strongly suggests that a congenital arterial defect
      may predispose to early rupture of these aneurysms.

PMID- 8303792
TI  - [The treatment of acromegaly].
AB  - Acromegaly is a rare disease which can significantly reduce life expectancy.
      Clinical features are diverse and the patient may consult a variety of medical
      and surgical specialists before the diagnosis is suspected. However, the disease
      is easily confirmed by the appropriate laboratory tests, namely GH and IGF1
      measurements. In most cases, acromegaly is secondary to a micro or
      macrosomatotrope pituitary adenoma. Those lesions are easily visualized by a
      pituitary CT Scan or Magnetic Resonance Imaging. Visual fields have to be
      evaluated by a neuro-ophthalmologist, and a thorough evaluation of other
      pituitary functions have to be performed. Selective removal of the adenoma by the
      transsphenoidal route is the treatment of choice for acromegaly. When performed
      by an experienced neurosurgeon, normalization of GH secretion can be expected in
      approximately 75% of cases. The surgical outcome is modulated by the volume, the
      extension of the tumor and the preoperative GH level. Octreotide, radiotherapy or
      bromocriptine are indicated whenever the patient remains with an elevated level
      of GH with persistency of symptoms.

PMID- 8303794
TI  - Are the birds feeding you Campylobacter?
AB  - During May and June 1992 there was a marked increase in reports of campylobacter
      infections compared with other years. Several affected patients mentioned they
      had been drinking milk from bottles previously pecked by birds. A case control
      study was initiated to investigate whether there was any significant association.
      It was concluded that drinking milk pecked by birds was associated significantly
      with subsequent campylobacter infection.

PMID- 8303795
TI  - The artificial urinary sphincter. A new solution for incontinent patients.
AB  - Treatment of urinary incontinence with the artificial urinary sphincter has been
      available in centres such as London and Liverpool for a number of years. This
      service is now available in the department of urology of the Belfast City
      Hospital. Twelve patients have had successful implantation of an artificial
      urinary sphincter for urinary incontinence, and ten are now fully continent. One
      patient with Wegener's granulomatosis developed active disease in his urethra
      which has precluded activation of the device. One patient has had the device
      removed because of erosion into the urethra.

PMID- 8303796
TI  - Childhood accidental deaths on farms in Northern Ireland.
AB  - Deaths to children on farms in Northern Ireland over a five year period are
      reviewed. There were seventeen such deaths, the majority of which involved farm
      machinery. The circumstances of the accidents are described in order to highlight
      the preventable aspects of these accidents.

PMID- 8303797
TI  - Huntington disease in County Donegal: epidemiological trends over four decades.
AB  - The prevalence rate of Huntington disease in County Donegal between 1961 and 1991
      showed a decrease from 4.4 to 1.6 per 100,000 population. Emigration and
      reduction in family size probably account for the progressive decline in
      prevalence. Over the same time period in the rest of Europe, prevalence has
      declined only gradually, or has remained static.

PMID- 8303798
TI  - A memoir of Dr Norman Joseph Ainley (1924-1962), and a last look at smallpox and
      vaccination.

PMID- 8303799
TI  - The Royal Group of Hospitals Arts and Environment Project.

PMID- 8303800
TI  - Peritoneal mesothelioma.

PMID- 8303801
TI  - Postsplenectomy sepsis: a lifelong risk.

PMID- 8303802
TI  - Myocardial infarction in association with misuse of anabolic steroids.

PMID- 8303804
TI  - Intravenous mercury: a three year follow-up.

PMID- 8303803
TI  - Odontoid peg metastasis from an oesophageal adenocarcinoma.

PMID- 8303805
TI  - MONICA/ECTIM meeting report: heart attacks in France and Northern Ireland. 23-24
      April 1993. Abstracts.

PMID- 8303806
TI  - Angiostrongylus vasorum infection in seven dogs.
AB  - Angiostrongylus vasorum infection was diagnosed in six dogs by the identification
      of larvae in sputum or faeces, or by the identification of adult worms post
      mortem. In another dog strong evidence of the condition was obtained but no
      parasites were identified. In four cases the main clinical signs were coughing
      and dyspnoea, but one dog had exercise intolerance and no history of coughing.
      One dog in which larvae were found in the faeces had no clinical signs that were
      related to the infection. Another dog had flaccid hindlimb paralysis and forelimb
      hypermetria-clinical signs of the disease which have not been reported
      previously. Four of the cases came from south Wales, one of them being the first
      case of the infection to be reported from this area.

PMID- 8303807
TI  - A comparison of evening primrose oil and sunflower oil for the management of
      papulocrustous dermatitis in cats.
AB  - Eleven cats with papulocrustous dermatitis were randomly assigned to one of two
      groups and supplemented with either evening primrose oil or sunflower oil for 12
      weeks. Clinical scores were assessed at intervals of three weeks and blood
      samples were taken for the analysis of plasma and erythrocyte fatty acid
      concentrations. The cats in both groups improved during the period of treatment
      and the concentration of linoleic acid in erythrocyte phospholipid increased in
      the cats fed evening primrose oil. Six weeks after the supplement was withdrawn
      the cats fed evening primrose oil had deteriorated less than those fed sunflower
      oil.

PMID- 8303808
TI  - Termination of early pregnancy in sheep with dinoprost or cloprostenol:
      comparison of two commercial preparations.
AB  - The response of the ovine corpus luteum of pregnancy to the luteolytic effect of
      prostaglandin F2 alpha (dinoprost) and its analogue, cloprostenol, was tested in
      both superovulated and untreated ewes by monitoring plasma progesterone
      concentrations at the time of 'material recognition' and beyond (days 13 to 30).
      On days 13, 16 and 28, the majority of the superovulated ewes were refractory to
      10 mg of dinoprost. The luteolytic efficacy of 250 micrograms of cloprostenol was
      compared with 10 mg of dinoprost on day 20 of pregnancy in superovulated and
      untreated animals and the two prostaglandins were also compared on days 26 and 30
      in animals previously unresponsive to dinoprost. Generally, cloprostenol was more
      effective than dinoprost because there was less refractoriness on day 20 and no
      refractoriness on days 26 and 30 to this prostaglandin. No difference in the
      sensitivity to this drug was found between the superovulated and untreated groups
      on days 20 and 26.

PMID- 8303809
TI  - Cryptosporidium infection in farm cats in the Glasgow area.

PMID- 8303810
TI  - Calfhood vaccination for dictyocaulosis.

PMID- 8303811
TI  - Accidents in practice.

PMID- 8303812
TI  - EHV-1 infection in twin equine fetuses.

PMID- 8303813
TI  - Urethral obstruction in a cat.

PMID- 8303814
TI  - Constraints on the enhancement of elimination of drugs with activated charcoal.
AB  - Both extracorporeal hemoperfusion through charcoal-containing columns and
      repeated oral administration of charcoal can accelerate clearance of some drugs
      or toxins from the systemic circulation. The efficacy of these 2 interventions is
      limited by a variety of factors, and the complex kinetic equations describing
      charcoal-induced clearance provide little practical clinical guidance about the
      potential efficacy of charcoal in accelerating clearance of a specific drug or
      toxin without previous empiric data. We derive here simple rules that place an
      upper limit on the maximal fraction of an absorbed dose of drug that can be
      removed (FRmax) by charcoal in terms of the volume of distribution (Vd), a
      parameter which is known for most drugs. For 4 h of hemoperfusion, a theoretical
      upper limit of FRmax is (1/Vd), where Vd is expressed in L/kg of body weight, and
      actual fractional removal (FR) will not exceed [1/(2 x Vd)]. Drug removal by 24 h
      of repeated po administration of charcoal exhibits similar relationships between
      FRmax and Vd, when charcoal-induced clearance derives primarily from removal of
      drug from blood perfusing in gastrointestinal mucosa. These relationships offer a
      simple means to evaluate the potential efficacy of acceleration of drug clearance
      by activated charcoal for drugs with a known value for Vd, and the relationships
      indicate that such interventions are impractical for drugs with very large values
      for Vd, such as tricyclic antidepressants.

PMID- 8303815
TI  - Oral vanadate and Tiron in treatment of diabetes mellitus in rats: improvement of
      glucose homeostasis and negative side-effects.
AB  - It has been shown that improvement of glucose homeostasis by oral vanadate or
      vanadyl treatment in streptozotocin-induced diabetic rats is accompanied by
      severe negative side effects (some deaths, decreased weight gain, alteration in
      renal function as well as tissue vanadium accumulation) which argue against the
      use of vanadium compounds in diabetes treatment. The present study was undertaken
      to assess the effectiveness in alleviating some signs of diabetes in
      streptozotocin-treated rats with oral therapy with sodium metavanadate (NaVO3)
      and sodium 4,5 dihydroxybenzene-1,3-disulfonate (Tiron), a chelating agent
      effective in mobilizing vanadium. In a preliminary experiment, diabetic rats were
      given aqueous solutions of 0.20 mg NaVO3/ml for 4 days. Vanadium-treated rats
      which showed blood glucose levels significantly lower (p < 0.001) than vanadate
      untreated diabetic rats were selected for subsequent experiments. These animals
      were given 0.20 mg NaVO3/ml in drinking water and 0, 125.6, 314 or 628 mg
      Tiron/kg/d by gavage for 2 w. Although most of the animals did not become
      normoglycemic, several characteristic signs of diabetes (hyperglycemia,
      hyperphagia and polydipsia) were alleviated by the NaVO3 treatment. The
      administration of 314 mg Tiron/kg/d (approximately 1 NaVO3: 5 Tiron, mole ratio)
      did not diminish the ameliorative effects of NaVO3 with respect to diabetes, but
      significantly decreased the level of vanadium accumulation in target organs.
      These results show that some of the beneficial effects of NaVO3 are maintained in
      diabetic animals given Tiron, while the administration of the chelator results in
      a significant decrease in tissue vanadium accumulation. Accordingly, this would
      diminish the possibility of toxic side effects derived from prolonged oral
      vanadium administration.

PMID- 8303816
TI  - Effect of experimental lead toxicity on cardiovascular function in calves.
AB  - The effect of lead was studied on cardiovascular function in calves given oral
      doses of 5 mg lead acetate/kg body weight daily till the appearance of clinical
      signs of toxicity. Arterial blood pressure and electrocardiogram were recorded
      before (day 0) and on days 30 and 60 of lead administration. There was a
      significant increase in arterial blood pressure in lead-intoxicated calves on day
      30 (124.8 +/- 1.0 mm Hg) with the peak values noted on day 60 (150.8 +/- 4.3 mm
      Hg). ECG in lead 11 showed marked increases in P wave duration and amplitude and
      duration of P-R interval. Duration of Q-T interval was decreased and T wave was
      inverted after 30 days of continuous lead exposure. Histopathological examination
      showed degeneration of cardiac musculature, mononuclear cell infiltration and
      swelling of Purkinjee fibers in calves sacrificed after the onset of irreversible
      signs of lead toxicity.

PMID- 8303817
TI  - Enhanced activated charcoal delivery through small-bore tubing.
AB  - Activated charcoal is often given through small-bore tubing for pediatric
      patients or in attempts to bypass the stomach in patients who are vomiting. The
      viscosity makes activated charcoal difficult to administer through small-bore
      tubing. This in vitro study examined several interventions to facilitate flow of
      aqueous suspension activated charcoal through the small-bore tubing. Aqueous
      suspension activated charcoal with or without sorbitol had similar flow rates.
      Precoating the tubing with mineral oil gave only minimal increases in flow rate.
      A 10% dilution decreased the time to administer 240 ccs of aqueous suspension
      activated charcoal by 2/3. An additional 10% dilution reduced the time to
      administer the same dose a further 50%. Minimal dilution of aqueous suspension
      activated charcoal with tap water greatly increased flow rate through small-bore
      tubes.

PMID- 8303818
TI  - Hepato-renal toxicosis characterized in sheep dosed intraruminally with snakeweed
      foliage (Gutierrezia spp).
AB  - To investigate the acute effects of snakeweed foliage (SW, Gutierrezia spp), 6
      ruminally fistulated wethers (avg BW 78.6 kg) were dosed intraruminally (2/dose)
      with 454 g ground SW foliage, 227 g SW + 227 g alfalfa, or 454 g alfalfa daily
      for 5 d. Rumen fluid and blood samples were collected daily before SW dosage, and
      on day 6 the animals were euthanized and examined. At d 5, SW increased direct
      and indirect bilirubin indicating impaired hepatocyte function with biliary
      involvement and cholestasis. Gamma-glutamyl transpeptidase concentrations were
      elevated, and pale yellowish enlarged livers were observed in SW-dosed animals.
      Serum creatinine concentrations were increased 2-fold by SW, suggesting renal
      impairment. Rumens from dosed animals were compacted with hemorrhagic and
      necrotic mucosa suggesting SW-impaired rumen motility and microbial fermentation.
      One wether dosed with 454 g SW died after SW dosage for 2 d.

PMID- 8303819
TI  - Permeability changes in the blood-brain barrier of neonate and adult rats after
      thiobencarb exposure.
AB  - Thiobencarb, an organocarbamate herbicide, induces toxic neuropathies in neonates
      and adults. Permeability changes in the blood brain barrier under thiobencarb
      stress in neonate and adult rats were assessed using the dye, trypan blue. Acute
      and subacute doses of thiobencarb increased the dye concentrations in the brains
      of both neonates and adults in a time dependent manner. Concentrations of the dye
      were found to be greater in neonate rat brains when compared to adult brains.

PMID- 8303820
TI  - A fungicide containing iminoctadine causes circulatory failure in acute oral
      poisoning.
AB  - We report a case of a 27-year-old man who ingested a fungicide containing
      iminoctadine with suicidal intent. He developed acute and severe circulatory
      failure which responded well to noradrenaline.

PMID- 8303821
TI  - Acute poisoning by pesticides: a prospective epidemiological study in a Spanish
      emergency service.
AB  - Our results were obtained from patients aged 15 y and above treated for pesticide
      poisoning at the Emergency Service of Elche General Hospital in south Alicante
      province during 1989. Among other epidemiological parameters, we evaluated the
      hospital prevalence of this type of poisoning and obtained a prevalence rate of
      0.17% of the total number of emergencies treated. The most frequent age group was
      between the ages of 45 and 54 y, the male to female ratio was 4:1 and there was a
      prevalence of married people. Professional accidental etiology was most common,
      and the lethal cases 5.1% were due to self-poisoning.

PMID- 8303822
TI  - The effects of nitrate, nitrite and N-nitroso compounds on human health: a
      review.
AB  - The effects of nitrate, nitrite, and N-nitroso compounds on human health are
      reviewed. Special emphasis has been placed on the role of these compounds on
      infant methemoglobinemia and gastric cancer. The discussion on methemoglobinemia
      includes the source of nitrate or nitrite, diagnosis, treatment, prevention and
      the contributions of age, gastric pH, gastrointestinal illness, and ingestion of
      vitamin C to this illness. The maternal transfer of these compounds and the
      potential effect on fetal death and malformation are also described. The etiology
      and development of gastric cancer is reviewed as well as the roles of nitrate,
      nitrite, and N-nitroso compounds in this disease. Endogenous nitrosation and the
      experimental and epidemiologic evidence linking these compounds to gastric cancer
      is examined. Other sections include adult methemoglobinemia and acute toxicity,
      hypo- and hypertension, Balkan nephropathy, slowing of motor reflexes in
      children, nitrate esters dependence. Sources of nitrate, nitrite, and N-nitroso
      compounds are detailed. Future areas of research are given.

PMID- 8303824
TI  - Attempt to develop a national poison control center movement.

PMID- 8303823
TI  - Intoxication due to Crotalaria retusa and C spectabilis in chickens and geese.

PMID- 8303825
TI  - On the hazards of being politically incorrect.

PMID- 8303826
TI  - Contribution of extrastriate area V4 to the surface-recorded flash VEP in the
      awake macaque.
AB  - This study compared striate and extrastriate contributions to the surface
      recorded flash VEP. Laminar visual evoked potential, current source density and
      multiunit activity profiles were obtained with multicontact electrodes from areas
      V1 and V4 in three awake macaques. As found earlier, the major striate
      contribution is to early (N40, P55-80) components. Major contributions to the
      later (N95, P120, Late Negativity) components arise from V4. Early, afferent
      triggered inhibition in V4 also produces a small contribution to N40. Response
      latencies in V4 vs V1 suggest an input to V4, bypassing V1, emphasizing a
      parallel processing component of visual system organization.

PMID- 8303827
TI  - Extrinsic current and flash sensitivity in turtle cones.
AB  - The effects of hyperpolarizing current and background light on intracellular
      responses of red cones in turtle were compared. Even though a background light
      always reduced response amplitude, hyperpolarizing current did so in only 25% of
      the cells studied. When hyperpolarizing current reduced response amplitude it
      also produced changes in response kinetics and the intensity-response
      relationships, but these changes differed from those produced by background
      light. Considerably greater hyperpolarization was required with current than with
      light to produce equivalent reductions in amplitude. The results suggest that
      current reduces amplitude by activating a membrane conductance, while background
      light acts through a different mechanism.

PMID- 8303828
TI  - Spatial phase discrimination in monkeys with experimental strabismus.
AB  - Human strabismus amblyopes show deficits in spatial vision that are revealed in a
      variety of visual tasks. In particular, they show severe deficits in their
      ability to encode the relative spatial phase of the sinusoidal components in a
      compound grating. To investigate the neural basis of strabismic amblyopia we
      tested the ability of monkeys with experimentally induced strabismus to encode
      spatial phase relationships. First, we trained them to discriminate between
      compound gratings (made of a fundamental sinusoid and its third harmonic) that
      differed only in the relative phase of their components. These monkeys exhibited
      a pattern of severe deficits that resemble those described in the human
      population of strabismic amblyopes. We conclude that these animals represent a
      valid model of strabismic amblyopia. Second, we show that a model that had been
      used to account for the performance of normal human subjects and of humans with
      anisometropic amblyopia fails to predict the performance of monkeys with
      strabismic amblyopia.

PMID- 8303829
TI  - The memorability and discriminability of primitive perceptual units in infancy.
AB  - Three-month-olds were operantly trained to kick to move a block mobile that
      displayed a horizontal and a vertical line ("textons") arranged as L, T, or + on
      each side. Delayed recognition was tested either 0, 1, 3, 5, 7, or 9 days later
      with either the same or a different display. Infants failed to discriminate
      between Ls and Ts after delays longer than 1 hr but discriminated both from +s,
      which contains an additional texton (the line crossing), after delays as long as
      7 days but not 9. Also, they remembered +s longer than Ls and Ts. These data
      indicate that the same primitive perceptual units that mediate adult texture
      segregation are differentially discriminated and differentially memorable in
      early infancy.

PMID- 8303830
TI  - Temporal integration of random dot apparent motion information in human central
      vision.
AB  - Human motion perception is assumed to be functionally described by an array of bi
      local detectors feeding later, higher order computational stages. Using this
      model as a guide, improvement of spatio-temporal displacement sensitivity by
      temporal integration (summation) was measured in human central vision using
      random dot pattern apparent-motion stimuli. Our results agree with previous
      experiments with regard to improvement of maximum perceivable spatial
      displacement but show that contrary to previous results the minimum perceivable
      spatial displacement can be improved in a similar manner. Furthermore, stimulus
      duration is a more accurate predictor of sensitivity than the number of frames in
      the stimulus over a wide range of stimulus parameter values. Finally, our results
      indicate that temporal tuning of motion detectors is inversely related to the
      size of the spatial pattern displacement.

PMID- 8303831
TI  - Ganglion cell pathways for rod vision.
AB  - Measurements of the acuity of rod vision made by two different techniques show it
      to vary only slightly with eccentricity. At eccentricities beyond 15 deg acuity
      is well predicted from the sampling properties of the mosaic of the P-class of
      ganglion cells. With decreasing eccentricity acuity falls progressively below the
      sampling limit of P-cells, but even at the lowest eccentricity examined (5 deg)
      does not reach the limit imposed by the sampling properties of the mosaic of M
      cells. At an eccentricity of 5 deg rod vision could be supported by as few as 20%
      of P-cells.

PMID- 8303832
TI  - Binocular mechanisms for detecting motion-in-depth.
AB  - There are in principle at least two binocular sources of information that could
      be used to determine the motion of an object towards or away from an observer:
      such motion produces changes in binocular disparities over time and also
      generates different image velocities in the two eyes. Existing psychophysical and
      physiological evidence is reviewed. It is concluded that these data are
      inconclusive concerning whether one or both of these sources of information are
      used in primate vision. Thresholds were measured for disparity modulations in
      dynamic (temporally uncorrelated) random dot stereograms (RDS), and for RDS in
      which the same random dot pattern was used throughout (temporally correlated).
      Although the first stimulus contains no consistent inter-ocular velocity
      differences, thresholds were generally slightly lower for this stimulus than for
      temporally correlated stimuli. Sensitivity to the temporal derivative of
      disparity is therefore adequate to account for human stereomotion detection. A
      stimulus was devised in which monocular motion was clearly visible to each eye
      (with opposite velocities) but in which all disparity changes were beyond the
      temporal resolution of stereopsis. This produced no sensation of motion-in-depth.
      Similarly, stimuli beyond the spatial resolution of stereopsis did not support
      stereomotion detection. These data strongly suggest that stereomotion is
      primarily detected by means of temporal changes in binocular disparity. We argue
      that there is no experimental evidence that supports the existence of a mechanism
      sensitive to inter-ocular velocity differences.

PMID- 8303833
TI  - Line intensity affects perceived shape.
AB  - A method for measuring the variation of one stimulus parameter with respect to
      another is applied to show how line intensity affects the perceived tilt of
      lines, internal angle of chevrons, and curvature of circular arcs. Perceived
      curvature increased with increasing line intensity, but analogous effects were
      found only for obtuse chevrons, not for acute ones, suggesting a limit to the
      range of orientations which contribute to the processing of curvature. The
      absence of a clear trend for tilted lines and acute angles highlights the
      specificity of the curvature findings. Explanations based on a computer model and
      other psychophysical and single-unit studies are examined.

PMID- 8303834
TI  - Active vision in honeybees: task-oriented suppression of an innate behaviour.
AB  - In a pattern discrimination task, bees tend to fly along the contours contained
      in the patterns, as revealed by an earlier study. As opposed to this, in a task
      involving the detection of an edge between two striped surfaces placed at two
      different ranges, the bees avoid contour-following, as revealed by the present
      study. The study shows that, in the latter task, the bees learn to suppress the
      otherwise innate contour-following behaviour and adopt a flight strategy that
      provides them with the motion parallax cues necessary to cope with this task.
      Thus, the animal's active behaviour determines the type of visual information to
      be extracted from the environment.

PMID- 8303835
TI  - Retinal eccentricity and the latency of eye saccades.
AB  - The latency-eccentricity function, for the first saccade towards a small green or
      red target on the horizontal hemi-retinal meridian, is bowl-shaped with a central
      latency peak, a minimum plateau from 0.75 to 12 degrees, and a gradual increase
      in latency towards the periphery. The function is highly reproducible and the
      central peak is a robust finding. For our step sizes and criteria its height is
      around 35-75 msec. Manipulations of target intensity and colour, or the state of
      adaptation by a retinal bleach, show that sensory contributions to the central
      peak are generally small (5-15 msec) for adequately suprathreshold targets.
      Beyond 35 degrees in the temporal retina (nasal visual field) latencies become
      erratic, even for bright green targets, and there are direction errors. Frequent
      direction errors occur over a much wider range of eccentricities for red targets
      that are 1 log above the foveal threshold for perception.

PMID- 8303836
TI  - Eye torsion elicited by oscillating gratings: effects of orientation, wavelength
      and stationary contours.
AB  - We studied binocular cyclorotatory (torsional) eye movements in response to
      gratings that oscillated sinusoidally in a frontal plane. The square-wave
      gratings viewed by the right and left eye were presented and controlled
      separately to induce cycloversion and cyclovergence by oscillation in phase and
      out of phase. Eye movements were recorded with scleral induction coils. Stimulus
      oscillation frequency ranged from 0.125 to 1 Hz and the wavelength of the
      gratings ranged from 0.92 to 25.75 deg of visual angle. Cycloversion and
      cyclovergence gain were, on average, comparable in magnitude and decreased with
      increasing oscillation frequency. There was no consistent effect of the
      wavelength on the magnitude of the responses. In general, responses were
      considerably higher to gratings that were oriented horizontally than to those
      oriented vertically. This anisotropy was present both in cycloversion and
      cyclovergence. It was enhanced in a larger sized stimulus and by presenting
      stationary, orthogonal contours (mimicking a "shear" movement), but it was not
      consistently influenced by wavelength. Cyclovergence showed a phase lag, which
      increased with oscillation frequency but which was independent of wavelength. In
      contrast, cycloversion showed a slight phase lead which was independent of both
      oscillation frequency and wavelength.

PMID- 8303837
TI  - Discrimination of changes in the second-order statistics of natural and synthetic
      images.
AB  - It has been suggested that the second-order statistics of different natural
      images are all remarkably similar and that neurones and channels in the visual
      system may exploit this similarity. We have measured the ability of human
      observers to discriminate changes in these statistics using different natural and
      synthetic stimulus images and have found that the dependence of their
      discrimination thresholds upon the reference second-order statistics is similar
      in form, for both kinds of stimuli. However, there is some variety in the
      magnitudes of the thresholds for the natural stimulus images; in fact, the second
      order statistics of different natural images are more diverse than previously
      suggested. The discrimination task can be modelled as the discrimination of
      changes in local contrast within restricted spatial frequency bands and is
      similar to the discrimination of blur.

PMID- 8303838
TI  - The Cardiff acuity test used for measuring visual acuity development in toddlers.
AB  - The Cardiff acuity test was used in estimating the binocular and monocular visual
      acuity norms of 231 toddlers between 12 and 36 months. Mean binocular acuity
      increased from 4.5 to 1.2 min arc and monocular acuity from 4.5 to 1.4 min arc
      over the age range. Interocular acuity difference was not significant and for 99%
      of the children, the difference in acuity estimate was < or = 1/3 octave. Success
      rates ranged from 96 to 100% for binocular tests but fell to a range of 41-91%
      for monocular testing. Acuity assessment was fast and the intraobserver
      reliability was high. Age norms of visual acuity useful in clinical settings are
      presented for toddlers between the ages of 12 and 36 months.

PMID- 8303839
TI  - Comparability of the death certificate and the 1986 National Mortality Followback
      Survey.

PMID- 8303841
TI  - [The basic statistical indices of the work of military dental polyclinics].

PMID- 8303842
TI  - [The bureaucratic approach to a study of the health of servicemen].

PMID- 8303840
TI  - [The deposition of scientific papers by military physicians].

PMID- 8303843
TI  - [A methodology for studying the health of military servicemen].

PMID- 8303844
TI  - [Current methods for the diagnosis and correction of valve failure in varicose
      veins and its recurrence].

PMID- 8303845
TI  - [Reconstructive operations on the arteries].
AB  - The article gathers the results of 714 complicated reparative operations on
      aorta, as well as iliac, femoral, and tibial arteries. The author formulated the
      principles of emergency angiosurgical care. Recommendations concerning surgical
      tactics in concomitant and multiple injuries are enclosed. The article proves the
      necessity to use various methods of revascularization of ischemic segments for
      simultaneous or consecutive treatment during a single hospitalization. The number
      of lethal cases came down to 5.8%, and postoperative complications--to 12.4%.

PMID- 8303846
TI  - [Specialized medical care in diffuse peritonitis].
AB  - The authors present a report concerning the system of operational and medico
      evacuation measures during the treatment of 168 patients with generalized
      peritonitis. During hospitalization the reactive phase was marked in 37 patients
      (22.1%), toxic and terminal--in 95 (56.5%) and 36 (21.4%) patients
      correspondingly. As a result of an adequate surgical and anesthetic intervention
      and complex therapy for generalized peritonitis the number of complications was
      diminished by 2.5 times (p 0.001), and lethal cases by 4.5 times (p 0.1).
      Realization of the principle of immediate specialized care is possible only in
      combination of adequate organizational and medical measures.

PMID- 8303847
TI  - [The radionuclide diagnosis of post-gastric resection disorders].
AB  - The article studies the possibilities of radionuclide method in disclosing the
      basic postgastroresectional syndromes: dumping syndrome, duodenogastric reflux
      and afferent loop syndrome. After resection of stomach 92 patients were examined
      throughout a period from 1 to 10 years. During dynamic scintigraphy of liver
      characteristic changes were disclosed in biliary secretory system which could
      have diagnostic significance. This method gives the possibility to determine the
      frequency, duration and volume of duodenogastric reflux. It was found out that
      Roux's [correction of Rue's] method of resection have resulted in minimal number
      of duodenogastric refluxes. Dynamic scintigraphy of stomach is useful for
      studying evacuative function of the resected stomach and for afferent loop
      syndrome diagnosis, which sometimes is more informative than a wide-spread barium
      sulfate roentgenological method.

PMID- 8303848
TI  - [The characteristics of the clinical picture, immunological indices and treatment
      of patients with acute pneumonia in sensitization of the body].
AB  - The peculiarities of the clinical picture in acute pneumonia in patients with
      sensibilization of an organism (pronounced rhino-conjunctival syndrome and more
      prolonged hyperthermic reaction in acute period, frequent aggravations of
      allergic process) require application of antiallergic therapy. Depending on the
      character of immunopathological reactions the complex treatment can be provided
      using administration of desensibilizing drugs, medications of non-specific
      desensibilization, natrium chromoglicate, corticosteroids, and sometimes
      plasmapheresis and hemosorption.

PMID- 8303849
TI  - [Errors and complications in computed tomography-guided biopsies].
AB  - The article analyses the results of 104 biopsies which were carried out in 84
      patients with different diseases of the organs of thoracic (50) or abdominal (16)
      cavities, postperitoneal space (32), bones and soft tissues (6). Positive results
      were obtained in 67 cases, negative--in 26, false-negative--in 11. The
      specificity was 70.3%, sensitivity--100%, authenticity--64.4%. The authors make a
      conclusion that the results and authenticity of biopsies depend on such factors
      as the proper organ to be punctured, character and structure of the affection,
      its location, volume and spreading, as well as the type of needles to be used.

PMID- 8303850
TI  - [The use of Navoban for managing nausea and vomiting during the aggressive
      chemotherapy of malignant neoplasms].

PMID- 8303851
TI  - [The diagnostic and treatment characteristics of diphtheria in troop units and
      military medical institutions].
AB  - Medical records of 876 servicemen of a young age who have suffered various forms
      of clinical diphtheria were analysed. (Lethal cases were marked in 52 cases-
      5.9%). A true clinical symptom complex for the diagnosis of diphtheria at pre
      hospital period is as following: fever, intoxication and febrinous tonsillitis.
      The main cause of unfavourable outcome of the disease depends on the affection of
      cardiovascular, central and peripheral nerve systems by diphtheritic exotoxin.
      The most frequent limitations during medical care were the following: error
      diagnosis of angina (41%), late hospitalization and late specific treatment,
      insufficient doses of antidiphtheric serum, inopportune diagnosis of severe
      aggravations (infectious toxic shock, pneumonia).

PMID- 8303852
TI  - [Methods for preparing and conducting special tactical briefings with medical
      service officers].
AB  - Tactico-special briefing is one of the effective forms of individual practical
      training of medical service officers in field conditions, on maps or terrain
      models. Depending on its instructional goals briefings are subdivided into
      training and control. During briefing all the trainees undertake a role of the
      same officer in command. The basic method of briefing is training with further
      analysis of their work as a commanding officer. Making the plot of training it is
      necessary to take into account that the tactico-special situation must correspond
      to the modern combat requirements and principle of medical support.

PMID- 8303853
TI  - [The importance of body phenotypic characteristics in assessing the sequelae of
      exposure to low doses of irradiation].

PMID- 8303854
TI  - [The effect of low doses of ionizing radiation on the human immune system].

PMID- 8303855
TI  - [The prospects for using foodstuffs for enhancing the body's radioresistance].

PMID- 8303856
TI  - [The clinico-functional status of the organs and systems in pilots who
      participated in the cleanup of the aftereffects of the accident at the Chernobyl
      Atomic Electric Power Station].

PMID- 8303858
TI  - [Ia. V. Villie--the officer in charge of organizing the medical support for the
      Russian Army in the War of 1812].

PMID- 8303859
TI  - [The 50th anniversary of the creation of the organs of military forensic
      expertise].

PMID- 8303857
TI  - [The current trends in improving the system of delivering medical care to light
      casualties and those with mild illness in the navy in wartime].

PMID- 8303860
TI  - [The characteristics of medical supplies under current conditions].
AB  - The present situation requires that medical supply system could make it possible
      to assure an adequate ratio in distribution of the resources, using stable
      economic links between all the subjects on the basis of objective economic laws.
      As the world experience shows the best form for this matter is wholesale trade of
      medications and medical technique. Nevertheless, it is impossible to implement
      this form of supply without detailed and complex researches in the field of
      economics for military medicine and pharmacy, and reconstructing on this basis
      the system of training of commanding officers for military medical supply.

PMID- 8303861
TI  - [The connection between insulin-dependent biosynthesis of cell membrane signal
      ATP with amiloride-sensitive Na+/H+-metabolism in human erythrocytes].
AB  - Plasma membrane signal ATP (psATP) was synthesized in response to the effect
      insulin (0.4 microgram/ml) in erythrocyte membranes, washed in 0.25 M sucrose and
      maintained in the mixture containing all the components required for aerobic
      phosphorylation. Biosynthesis of psATP was completely inhibited by amiloride at a
      concentration of 2 x 10(-3) M. Ouabain (0.5 x 10(-6) M) inhibited the
      triphosphate synthesis by 95%. Monensin (0.3 x 10(-6) M) activated ATP formation
      2-fold approximately in erythrocyte membranes both stimulated by insulin and free
      of the hormone effect. Monensin, added into the incubation mixture simultaneously
      with ouabain, abolished its inhibitory effect on psATP synthesis. In absence of
      Na+ the psATP biosynthesis was not detected. Protonophore FCCP stimulated the
      biosynthesis at various concentrations from 10(-7) to 10(-3) M. These data
      indicated that biosynthesis of psATP is related to Na+/H+ metabolism in plasma
      membranes of human erythrocytes.

PMID- 8303863
TI  - [Disorders in metabolism of superoxide radicals in tumor-bearing mice during
      development of Ehrlich ascites carcinoma and their normalization under the effect
      of ruboxyl].
AB  - Activity of the systems involved in generation and utilization of superoxide
      radicals was studied in microsomes, mitochondria and nuclei of liver tissue from
      intact mice, mice with developed Ehrlich ascites carcinoma and of the animals
      treated with antitumoral drug ruboxyl. The ratio between the rate of superoxide
      radicals formation and activity of superoxide dismutase (SOD) served as specific
      characteristic of the O2(-)-SOD system in the corresponding compartments. During
      tumoral development, the pattern studied was altered in all the subcellular
      organelles used, thus demonstrating an impairment of free radical oxidation
      status in liver tissue of tumor-bearing animals. Administration of ruboxyl into
      healthy animals led to distinct increase in this ratio in mitochondria, while the
      drug normalized patterns of the O-(-)-SOD system in all the cell compartments
      studied in tumor-bearing animals. Ruboxyl appears to exhibit regulating effect on
      free radical oxidation.

PMID- 8303862
TI  - [Level of fructose-2,6-bisphosphate and activity of fructose-1,6-bisphosphatase
      in hepatocyte suspensions in streptozotocin diabetes].
AB  - Content of fructose-2,6-bisphosphate was drastically decreased (about 5-fold) in
      hepatocyte suspension obtained from rats with streptozotocin-induced diabetes, as
      compared with that of control animals. At the same time, activity of fructose-1,6
      bisphosphatase was increased 2-fold in these hepatocytes. Incubation mixture of
      the hepatocytes from the diabetes impaired animals contained only low amounts of
      lactate.

PMID- 8303864
TI  - [The role of free radical reactions in the effect of ethanol on the central
      nervous system].

PMID- 8303865
TI  - [Lipid spectra of various zones of the myocardium, damaged by infarct, as a
      reflection of its metabolic and functional activity in the period preceding the
      lethal outcome of the illness].
AB  - Lipid composition was studied in various zones of the myocardium impaired with
      infarction. Content of phospholipids was decreased, while lysophospholipids and
      free fatty acids were increased in the necrosis-impaired sites. In the
      overinfarction-impaired tissues content of total lipids, triglycerides,
      cholesterol and its esters and free fatty acids was elevated but some
      phospholipids were decreased (cardiolipins, phosphatidyl ethanolamine and
      sphingomyelins). Alterations in lipid composition observed in necrosis impaired
      myocardial tissues appear to occur due to destruction of cardiomyocytes, to the
      following liberation of enzymes from the cells and their irregular effects on
      lipid metabolism. There were apparently three types of reactions in the
      overinfarction-impaired sites: hydrolysis of lipids, decrease in the rate of
      fatty acids oxidation and increase--in synthesis of individual lipid classes. All
      the alterations detected were related to deficiency in oxygen, accumulation of
      NADH2, NADPH2 and factate. This suggests that activation of biosynthesis of free
      fatty acids and lipids, directed to neutralization of the dehydrogenase coenzymes
      and to continuation of glycolysis, may be involved in positive compensation
      adaptive reactions during definite steps of the disease development. However,
      during the further steps of the disease increase in content of free fatty acids
      and other lipids in blood and tissues, as in the case of lactate, may aggravate
      the pathological state, acquired dysfunction and increased the necrosis-impaired
      zone. The data obtained suggest that analysis of lipid spectrum in various
      myocardial tissues may exhibit the rate of hypoxic and ischemic alterations,
      demonstrated the reserves of metabolic activity as well as showed the risk of
      necrosis enlargement during the prelethal period of the disease.

PMID- 8303866
TI  - [The role of disruption of lipid metabolism in mechanisms of the hepatotoxic
      effects of cisplatin].
AB  - Distinct alterations in the metabolism of lipids and phospholipids as well as
      activation of lipid peroxidation in liver tissue were detected in mice after
      administration of a new antitumoral drug cisplatin at a dose of LD50 (13.5 mg/kg)
      or after the course treatment within 5 days using 1/5 LD50. Content of malonic
      dialdehyde, diene conjugates and Schiff bases was increased, while the
      phospholipid composition was altered and concentration of membrane-toxic
      ingredients was increased. When the effects of cisplatin, administered at a dose
      of LD50 and during the course treatment, were analyzed more pronounced
      impairments of lipid metabolism were found during 7-15 days in mice treated with
      the drug at LD50. However, the drug toxic effect was manifested earlier during
      the course of treatment and in some cases it maintained for a long time (up to 30
      days of the experiment). The data obtained suggest that correction of the
      cytostatic-induced impairments in liver tissue functions may be carried out by
      means of the anti-radical drugs.

PMID- 8303867
TI  - [The effect of Ca2+ and Mg2+ on the superprecipitation reaction and activity of
      actomyosin ATPase in the myometrium].

PMID- 8303868
TI  - [Rat brain lipid peroxidation system under conditions of emotional-pain stress of
      varying duration].
AB  - Neurotization of rats, developed after long-term emotional-painful stress,
      resulted in activation of lipid peroxidation in brain both within 2 days and 8
      days of stress interruption. Compensative activation of the antioxidative
      protective system in response to increase in lipid peroxidation rate was not
      observed especially in synaptosomes. Activation of glutathione peroxidase, which
      is involved in adaptation, was accompanied by inhibition of superoxide dismutase
      and glutathione transferase. Thus, the balance was impaired between the rate of
      lipid peroxidation and the mechanisms of antioxidative protection.

PMID- 8303869
TI  - [Features of metabolism of the human myocardium during alcoholic intoxication].
AB  - Systems of alcohol oxidation, malate-aspartate shunt, content of total and alpha
      cholesterols in heart muscle and blood as well as morphometry of aorta were
      studied. The tissues investigated were obtained post mortem in lethal traumatic
      injury accompanied by increased content of ethanol in blood. The potentiating
      effect of alcoholization on atherogenesis was not found.

PMID- 8303870
TI  - [The effect of hypoxia on membrane status and lipid peroxidation in rat lungs and
      blood].
AB  - A state of lysosomal membranes and lipid peroxidation were studied in rat lungs
      under hypoxic conditions at the height 9,000 m, 3 hrs. Under these condition
      content of protein in lungs was decreased by 12% but free activity of lysosomal
      peptide hydrolases was simultaneously increased by 66%, indicating the lysosomal
      membranes labilization. At the same time, content of lipid peroxidation products-
      diene conjugates and Schiff bases, was decreased in lung synchronously with
      activation of the antioxidant enzymes catalase and superoxide anion dismutase.
      The lung tissue appears to have more powerful mechanisms of adaptation to
      deficiency of oxygen as compared with other tissues. Under hypoxic conditions
      content of protein in blood serum was similar to that of control values, while
      activity of lysosomal enzymes was increased by 26%, which occurred apparently due
      to an increase in the rate of lipid peroxidation. Actually, amount of lipid
      peroxidation products was increased in erythrocyte membranes but activity of SOD
      was not altered and the activity of catalase--tended to decrease. Thus, one of
      possible reasons of lipid peroxidation product accumulation in blood may be a
      lowered activity of the antioxidative enzymes.

PMID- 8303871
TI  - [The use of sodium gamma-oxybutyrate and gutimine for decreasing metabolic
      disorders in the heart, caused by exotoxic shock in acetic acid poisoning].
AB  - Exotoxic shock was simulated in non-linear rat males anesthetized with barbital
      after intragastric administration of 70% acetic acid at a dose of 4 ml/kg using a
      gastric tube. Energy metabolism and the rate of lipid peroxidation were studied
      in heart muscle during the decompensated and terminal periods of exotoxic shock.
      Sodium hydroxybutyrate (200 mg/kg) and gutimine (75 mg/kg), administered alone
      within 30 min after the poisoning, prolonged the period before manifestation of
      the decompensated and terminal steps of the shock; these drugs decreased the rate
      of metabolic impairments in the myocardium by decreasing the rates of adenine
      nucleotide catabolism, of glycolysis, lipolysis and lipid peroxidation.

PMID- 8303872
TI  - [Level of peptides in blood serum in experimental traumatic illness].
AB  - A procedure, developed for quantitative estimation of peptides in protein free
      blood serum, involved registration of products formed after reaction of peptide
      amino groups with o-phthalic aldehyde. The procedure developed was 50-100-fold
      more sensitive than spectrophotometry. Content of peptides in blood was altered
      depending on the steps of traumatic disease development. The concentration of
      peptides correlated with the composition of proteins in the serum.

PMID- 8303873
TI  - [Disruption of chemomechanical coupling in cardiomyocyte myofibrils in L-tyroxine
      toxicosis and athyreosis].
AB  - Skin assay of dog myocardial fibers showed alterations in free energy of ATP
      hydrolysis correlated distinctly with the rate of activity generated by the fiber
      (r = 0.87; P < 0.01). Impairment of chemomechanical coupling occurred in the
      system of myocardial contractile proteins under conditions of athyreosis and L
      thyroxin-induced toxicosis, which is responsible for qualitative and quantitative
      deteriorations of energy transformation in cardiomyocyte myofibrils. The sites of
      energy generation and liberation appear to be spatially disconnected in the
      active actomyosin complex and their coupling and uncoupling is related to
      properties of actin.

PMID- 8303874
TI  - [The effect of stretching on mechanical chemical characteristics of tissues from
      elongated extremities].
AB  - A number of biochemical patterns of blood serum were used as markers of the major
      components of cartilage and muscle tissues, which exhibited adequately the
      property of responses occurred in these tissues during elongation of an extremity
      by the Ilizarov's procedure. The content of these components was shown to
      correlate in dog blood serum and tissues. At the same time, the rate of
      hydration, concentration of proteoglycans and elastic properties of the joint
      cartilage were studied.

PMID- 8303875
TI  - [Immunoenzyme analysis of chorionic prealbumin in blood serum from donors and
      pregnant women].
AB  - Two-point ELISA was developed for determination of human chorionic prealbumin
      (hCPA). The sensitivity of this method was equal to 5 ng/ml. Content of hCPA was
      determined in blood of donors and women with normal pregnancy. Possible elevation
      in sensitivity and specificity of the ELISA in hCPA estimation is discussed.

PMID- 8303876
TI  - [Detection of combined forms of hemoglobino- and enzymopathies in newborns].
AB  - In order to develop a rational and early detection of combined forms of
      hemoglobin and enzymopathies, 1500 samples of neonatal cord blood were tested for
      alpha- and beta-thalassemia, of abnormal hemoglobins S and C, of
      methemoglobinemia and for hereditary persistence of fetal hemoglobin as well as
      428 samples were examined for glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and
      glutathione reductase (EC 1.6.4.2) deficiencies. For this purpose,
      isoelectrofocusing in Multiphor-2117 polyacrylamide-ampholine plates (LKB,
      Sweden) at pN 3.5-9.5 and pH 5.5-8.5 was carried out with subsequent laser
      densitometry of gels (Densitometer 2202, LKB). The data obtained were analyzed
      simultaneously in biochemical, hematological and genealogical studies. Hereditary
      impairments detected were evidenced by genealogical analysis.

PMID- 8303877
TI  - [Isoprotein composition of alpha 1-antitrypsin, haptoglobin, transferrin, and
      lipid peroxidation in the blood in inflammatory lung diseases in children].
AB  - Relationship was studied between the polymorphism of alpha 1-antitrypsin (Pi),
      haptoglobin (Hp) and transferrin and the development of chronic unspecific
      impairment of children lungs. Combination of protein isoforms PiM3M3 and Hp 1-1
      was found to increase the risk of the lungs unspecific impairments in persons
      with lingering pneumonia and caused more severe development of the disease.
      Relatively low activity of the isoform PiM3M3, as compared with other forms of
      the PiMM system, and more intensive and nonadequate rate of lipid peroxidation in
      patients containing HP 1-1 appear to be responsible for aggravation of these
      impairments.

PMID- 8303878
TI  - [Activity of the xenobiotic metabolism system under the effect of chemical
      pollution of the atmosphere and water].
AB  - Functional state of the system involved in biotransformation of xenobiotics in
      animal liver tissue was studied under conditions of combined chemical
      contamination of atmospheric air and water simulating the typical real loading.
      The model loading studied caused in some cases an induction of the microsomal
      monooxygenases without activation of UDP-glucuronosyl transferase, but
      simultaneously with accumulation of malonic dialdehyde; this suggests that
      metabolic alterations observed may be involved in development of pathology.

PMID- 8303879
TI  - [Anphen and energy status of the animal body].
AB  - Energy status of rats was altered after administration of anphen [2,4-(hydroxy
      3,5-ditretbutyl phenyl)-2-aminomalonic acid] at a dose of 40 mg/kg. Within 30 min
      after administration, maximal rates of NAD-dependent substrates and succinate
      oxidation were detected in liver mitochondria, which appears to occur due to
      activation of the mitochondrogenesis. The rate of electron transport in
      respiratory chain of mitochondria was decreased 1.3-1.6-fold within 1-1.5 hr,
      whereas within 3 hrs the patterns of oxidation and energetic coupling in liver
      mitochondria were reduced to control values. The similar alterations were
      observed in activities of lymphocyte alpha-glycerophosphate- and succinate
      dehydrogenases. Shifts in the pool of lipid peroxidation products in biological
      membranes was apparently responsible for alterations in activity of the energy
      metabolizing enzymes in lymphocytes and liver mitochondria.

PMID- 8303880
TI  - [Regulation of lipid metabolism in blood of weaving shop workers (noise level of
      about 90 dB A) by alpha-tocopherol acetate].
AB  - alpha-Tocopherol acetate, used for repeated treatment within a year of weavers
      working under highly uncomfortable conditions (the level of noise up to 90 dB),
      was shown to exhibit the regulating effect on the rate of lipid peroxidation and
      on content of alpha-tocopherol and cholesterol in blood plasma and erythrocyte
      membranes as well as on the ratios alpha-tocopherol acetate/total lipids, alpha
      tocopherol acetate/cholesterol in blood plasma and cholesterol/alpha-tocopherol
      acetate in erythrocyte membranes. The vitamin decreased distinctly the
      atherogenicity coefficient; these data suggest that treatment with tocopherol is
      essential for prophylaxis of noise-produced impairments.

PMID- 8303881
TI  - [The immunization of elderly people against influenza].

PMID- 8303882
TI  - [Approaches to modelling the prognosis of enterovirus infectious morbidity].

PMID- 8303883
TI  - [The isolation and characteristics of monoclonal antibodies to recombinant
      proteins of HIV-1 and HIV-2--the env and gag gene products].
AB  - Ten hybridomas secreting monoclonal antibodies (Mab) against recombinant HIV-1
      and HIV-2 antigens were produced (3 Mab anti-gag protein, 2 anti-env1, and 5 anti
      env2). In the immunoblotting assay all the anti-gag Mabs reacted with HIV capsid
      protein p24, whereas one of them reacted also with p55 protein and with 7 other
      polypeptides. Another anti-gag Mab cross-reacted with the antigen of
      subpopulation of human peripheral blood lymphocytes. The third one interacted
      with the antigen of both HIV-1 and HIV-2. All the 10 Mabs interacted with natural
      HIV antigens and can be used for identification and differentiation of HIV-1 and
      HIV-2.

PMID- 8303884
TI  - [Antibodies to the structural proteins of the measles virus studied in some
      chronic diseases].
AB  - The qualitative and quantitative analysis of antibodies to measles virus (MV)
      structural proteins (SP) in sera from patients with chronic glomerulonephritis
      (CGN), chronic active hepatitis (CAH), and liver cirrhosis (LC) was done. The
      patients were shown to have neutralizing antibody titres (NAT) higher than those
      in healthy subjects. An analysis of antibodies to SP was carried out by the
      radioimmunoprecipitation assay. Antibodies were detected to hemagglutinin,
      nucleoprotein (NP), fusion protein and to matrix protein (M) both in sera from
      the patients with these chronic diseases, healthy subjects, and patients with
      active measles. (The two latter groups were selected for comparison). However,
      some patients with CAH and LC had no antibodies to M protein in spite of very
      high NAT. The quantitative analysis of MV antibodies to SP was done only for NP
      because this antibody had the least individual variations. The quantity of anti
      NP antibodies was higher in most sera from patients with chronic diseases than in
      those from healthy subjects, and reached the level of that in patients with
      active measles. The presence of MV genome in the peripheral blood lymphocytes
      from patients CAH, CGN, and LC had been shown earlier. So it is assumed that MV
      persists in lymphoid tissue where the expression of all SP genes is realized.

PMID- 8303885
TI  - [The risk factors for the transmission of HIV infection among intravenous
      narcotic users in Russia].
AB  - Blood sera (316,281 specimens) from registered drug and toxic substance addicts
      were examined revealing no subjects seropositive to HIV. A special
      epidemiological questionnaire was developed and used for questioning of 86 drug
      addicts using drugs prepared domestically by the intravenous route. The group
      included 56 men and 30 women varying in age from 17 to 33 years. Lack of
      registered cases of HIV infection among drug addicts in Russia was explained by
      some peculiar features of using drugs. Intravenous inoculation of drugs with the
      same syringe and needle without sterilization, and large numbers of sexual
      contacts without the use of condoms suggest that as soon as HIV gets into this
      environment it will spread very rapidly.

PMID- 8303886
TI  - [The determination of the genotype of laboratory reassortants of the influenza A
      virus by competitive dot hybridization].
AB  - The genotype of laboratory reassortants produced by co-cultivation of virulent
      A/USSR/2/85 (H3N2) virus and multi-passaged attenuation donor A/Leningrad/9/46
      virus (H1N1) was determined by two different methods: a method of competitive dot
      hybridization (CDH) and polyacrylamide gel electrophoresis (PAGE) with virion
      RNAs urea. The results of the two methods were shown to be completely identical
      which confirmed the potential of using CDH method for genetic typing of influenza
      A virus reassortant strains.

PMID- 8303887
TI  - [An analysis of the potential areas of recombination in the hemagglutinin genes
      of animal influenza viruses in relation to their adaptation to a new host--man].
AB  - The authors tried to decode the mechanism of influenza viruses species adaptation
      in the process of host changing. The functionally important replacement in the
      surface pocket domains were revealed, particularly in the conservative region 221
      241, involving fibronectin-like part. Close replacements were revealed in the
      region 141-161. The method of construction of heteroduplexes between
      hemagglutinin RNA of duck, pig, and human viruses was used. The method showed
      that all heteroduplexes formed recombinogene structures. An unexpected effect of
      directional recombination was elicited for hemagglutinin RNA heteroduplexes in
      cases of duck-pig and human-pig viruses. During the directional recombination the
      following processes took place: the receptor-binding site of animal type was
      transmitted to the duck virus, while the human receptor-binding site was
      transmitted to the pig virus. According to the experimental data, a new
      hypothesis is formulated: the cascade mechanism of directional recombination for
      duck, animal and human viruses makes it possible for the recombinant viruses to
      overcome interspecies barriers.

PMID- 8303888
TI  - [The genomic variability of adenovirus serotype 3].
AB  - Genetic heterogeneity and evolutionary relationships among selected strains of
      adenovirus type 3 (Ad3) isolated in the former USSR (1976-1988) were examined
      using the restriction endonuclease Cfr131 with a 4-base recognition cleavage
      site. The population of adenovirus type 3 showed significant genetic instability.
      Evolution of genomic variants of Ad3 was found to have regional localization
      associated with definite periods of adenovirus circulation.

PMID- 8303889
TI  - [The isolation and in-vitro cultivation of a virulent strain of the porcine
      transmissible gastroenteritis virus].

PMID- 8303890
TI  - [The use of immunostimulants for enhancing the immunogenicity of a herpes
      vaccine].
AB  - National immunostimulators and interferon inducers (poludan, ridostin, larifan,
      myelopide, vegetan) in combination with a commercial herpes vaccine (HV) were
      used for experimental immunization of mice. A 3-fold or greater rise of specific
      antibody titres was observed after a single immunization of intact BALB/c mice.
      In experiments in chronically infected animals a single inoculation of HV
      resulted in a 3-fold rise of specific antibody titres at 6 days postimmunization
      but not in later periods (20, 30 days). Administration of larifan, an interferon
      inducer, but not the immunostimulator myelopide, induced a synergic effect in
      these experiments. Activation of alpha-interferon production was observed early
      after combined use of HV and immunostimulators. It is concluded that combined
      experimental use of HV and immunostimulators activated both specific antibody
      production and interferon production.

PMID- 8303892
TI  - [The etiological structure of acute respiratory infectious morbidity based on the
      data from a rapid diagnosis in Minsk].
AB  - Examination of 60,792 residents of Minsk in different seasons of 1977-1989 by
      indirect immunofluorescence showed this method to be able of recoding not only
      mono- but also polyetiological epidemics. The epidemic threshold for influenza A
      is 15% of positive findings, for influenza B is 7-8%, for polyetiological
      epidemics (influenza A and B) is 15-16% and 9-10%, respectively. The criterion of
      the epidemic situation in the city is a twofold increase (or higher) in the level
      of influenza A and B virus antigen findings in rhinocytological preparations as
      compared with the previous week.

PMID- 8303891
TI  - [A trial to produce an inactivated Lassa fever vaccine].
AB  - A single and double immunization of Papio hamadryas monkeys with an inactivated
      concentrated purified adsorbed preparation of Lassa virus in doses of 0.5-1.0 and
      1.1-2.1 mg by protein, respectively, protected the animals against the
      development of the disease and occurrence of viremia after an intramuscular
      challenge with 0.4 PFU dose. Upon aerogenic infection of monkeys protection of
      50% of the animals was achieved by a single immunization with the inactivated
      preparation in a dose 1.1 mg by protein.

PMID- 8303893
TI  - [A rapid solid-phase immunoenzyme method in the diagnosis of viral infections].
AB  - An accelerated solid-phase enzyme-immunoassay has been developed which permits
      identification of antigens and antibodies to them within 30-40 min, even directly
      at the site of specimen collection. The method was tested on the models of foot
      and-mouth disease virus, vesicular disease of swine, vesicular exanthema of
      swine, Aujeszky's disease, leukemia, and coronavirus infection of cattle.

PMID- 8303894
TI  - The shift toward healthier dining: a war in the trenches.

PMID- 8303895
TI  - Prevalence of daily and experimental smoking among University of Wisconsin
      Madison undergraduates, 1989-1993.
AB  - Limited information is available on smoking among college students. This study
      surveyed smoking prevalence and frequency among University of Wisconsin-Madison
      undergraduates aged 17 to 22 (n = 6,069) during the years 1989 through 1993.
      Sampling was conducted before and after the implementation of a smoke-free campus
      policy. Daily smoking remained constant across the 5 years at just under 10% of
      the sample; males showed a trend toward increased daily smoking (7.8% to 11.7%),
      while females showed a declining trend (10.2% to 8.4%). Additionally, 27% engaged
      in experimental smoking (smoking every few days, weeks, or months), resulting in
      a disturbing overall rate of tobacco use: about 37% of all students. These data
      indicate a need for more directed efforts to help university students overcome
      the threat of tobacco addiction.

PMID- 8303896
TI  - Smoking cessation among pregnant women in an urban setting.
AB  - This paper examines a study of a brief contact smoking cessation program among 57
      pregnant women at two urban clinics. All subjects were administered either a
      specially created videotape or a booklet on the topic of smoking. Subjects were
      then randomly assigned to receive either a nurse counseling message or to receive
      their usual care at the clinic. There was no statistically significant difference
      in smoking status among those who received either type of media or nurse
      counseling intervention. However, smoking cessation at one month after entry in
      the study was reported by 12% (N = 7) of subjects, by 18% (N = 10) of subjects in
      the ninth month of pregnancy, and by 9% (N = 5) of subjects at one month post
      partum. Over half of the patients attempted to quit smoking in the first month
      and 68% (39/57) made at least one quit attempt during the entire study period.
      Our results suggest that future smoking cessation programs and methods need to
      consider more intensive nursing interventions and supportive measures to produce
      lasting changes in smoking prevalence.

PMID- 8303897
TI  - The effect of maternal cigarette smoking on low birth weight and preterm birth in
      Wisconsin, 1991.
AB  - Cigarette smoking is one of the most preventable causes of low birth weight in
      the United States. This paper presents new data on the relationship between low
      birth weight and maternal cigarette smoking in Wisconsin based on an analysis of
      1991 birth certificates. In Wisconsin in 1991, 22.5% of mothers reported smoking
      cigarettes during pregnancy. Mothers who smoked cigarettes were twice as likely
      to bear low birth weight infants as were non-smokers. Low birth weight accounted
      for 49% of newborn hospital charges totaling $60.7 million. A 50% reduction in
      maternal smoking could potentially save $5 million in newborn hospital costs. A
      women is more likely to quit smoking during pregnancy. Physicians are in a unique
      position to encourage positive behavior change that will reduce the risk for low
      birth weight and have long term benefits for her and her family.

PMID- 8303898
TI  - Recent trends in cigarette smoking and per capita sales in Wisconsin.

PMID- 8303899
TI  - A new public health strategy to control the hazards of tobacco use.

PMID- 8303901
TI  - Wisconsin's experience with the national nicotine patch giveaway.

PMID- 8303900
TI  - Availability of cigarettes to under-age youth in Fond du Lac, Wisconsin.
AB  - Ninety-three percent of surveyed Fond du Lac School District students reported
      cigarettes as being "fairly easy" to "easy" to obtain. Easy access to cigarettes
      from retail outlets may be instrumental in the inordinately high local prevalence
      of under-age smoking. Fourteen-year-old youths were trained to attempt purchases
      of cigarettes from all cigarette outlets in the city of Fond du Lac. Information
      relating to the purchase attempts was recorded and analyzed. Our 60% purchase
      success rate stems from purchases at 77% of vending machines and 43% of over-the
      counter outlets. Sales from taverns accounted for approximately 25% of the
      totals. Our results are consistent with other studies and argue for retailer
      education and systematic enforcement of policies that address underage purchase
      of cigarettes from licensed outlets including those that otherwise proscribe
      minors from entering.

PMID- 8303902
TI  - Physicians are not alone: anti-smoking materials are available from the Tri
      Agency Coalition on Smoking.

PMID- 8303903
TI  - Cardiovascular diseases in India.
AB  - India is undergoing an epidemiological transition and is on the threshold of an
      epidemic of cardiovascular disease. Cause-specific mortality data indicate that
      cardiovascular disease is already an important contributor to mortality.
      Demographic projections suggest a major increase in cardiovascular disease
      mortality as life expectancy increases and the age structure of the growing
      population changes. Surveys in urban areas suggest that coronary risk factors are
      already widespread and that urgent action is needed to prevent a further rise as
      socioeconomic development proceeds. It is vital to obtain epidemiological data
      from several regions in order to plan, initiate and monitor public health action.

PMID- 8303904
TI  - The cardiovascular disease situation in Seychelles.
AB  - A rising frequency of cardiovascular diseases and related risk factors has been
      documented in Seychelles. This epidemiological transition to chronic diseases is
      believed to result from the aging of the population and from changes in lifestyle
      associated with a rapidly improving standard of living. Since 1990 a long-term
      national collaborative programme has been established for the prevention and
      control of cardiovascular diseases. It has been designed with a view to
      implementing a combination of population-based and specific, high-risk target
      group strategies. Objectives have been formulated, and culturally acceptable
      multisectoral activities have been devised, along with plans for the monitoring
      of cardiovascular diseases and risk factors and for the evaluation of the
      programme as it proceeds.

PMID- 8303905
TI  - The changing pattern of cardiovascular diseases in China.
AB  - In China, morbidity and mortality attributable to cardiovascular disease
      increased rapidly from the 1950s to the 1980s due to an increased life expectancy
      and changes in lifestyle. Cardiovascular disease has become the leading cause of
      death in the country. There is a high incidence of stroke, which is the commonest
      or second commonest cause of death. Hypertension, the main risk factor for stroke
      and an important risk factor for coronary heart disease, is the most prevalent
      cardiovascular disease, and should be given first priority in control programmes.
      Smoking, a common habit in males, is to be a principal focus of preventive
      activities over the next few years. Between 1970 and 1990, several community
      programmes for the prevention and control of cardiovascular diseases were
      established. The WHO MONICA Project has developed standardized methodologies that
      are used to establish systems for monitoring and evaluating control programmes.
      There is an urgent need to develop a long-term national strategy for the
      management and control of cardiovascular diseases.

PMID- 8303906
TI  - The pattern of cardiovascular disease in Indonesia.
AB  - As its socioeconomic situation is improving, Indonesia is now in epidemiological
      transition, having the double burden of infectious diseases and emerging
      noncommunicable, especially cardiovascular, diseases. A review of the data from
      recent community surveys indicates an increase in cardiovascular diseases,
      particularly ischaemic heart disease and hypertension and its sequelae, as causes
      of morbidity and mortality, most markedly among the elderly, while rheumatic
      heart disease and congenital heart disease continue to have much lower
      incidences. In response to this situation, Indonesia has joined the WHO MONICA
      Project as an associate member. The first population screening, completed in 1988
      on 2,073 randomly selected subjects, disclosed important risk factors including
      hypertension, smoking and physical inactivity. Lipid values are low compared with
      Western figures but higher than Japanese values. The prevalence of hypertension
      ranged from 5 to 15% in all adults but reached over 20% in those aged 50 years
      and over. Primary and primordial prevention programmes are to receive higher
      priority, and health education is to be given special attention at all levels. It
      will be necessary for the government to work closely with nongovernmental
      organizations in order to accomplish the tasks in hand.

PMID- 8303907
TI  - Cardiovascular disorders in Africa.
AB  - The availability of basic and reliable data on cardiovascular problems in
      Africans is limited and this hinders the presentation of a comprehensive review
      of the subject. Nevertheless, there is a strong suggestion that the spectrum and
      pattern of cardiovascular disorders in Africa is rapidly becoming
      indistinguishable from that observed in developed countries. The classic risk
      factors appear to be on the rise and smoking may attain levels equal to or
      exceeding those in many developed countries. Infectious and inflammatory
      cardiovascular conditions may still be the most common, although limitations in
      the technology available for accurate diagnosis make this difficult to verify.
      Rheumatic fever and rheumatic heart disease remain common, and the potential for
      educational and other preventive strategies is being realized in many countries.
      Hypertension at frequencies exceeding 5-10% in most rural areas and 12% in most
      urban areas, together with complications such as stroke, heart failure and renal
      failure, are leading causes of morbidity and mortality. Hypertension is the major
      public health problem in most African countries. The cardiomyopathies are a
      common problem, and the limited availability of specific diagnostic procedures is
      matched by limited therapeutic options for most Africans. The prevalence of
      atherosclerosis and coronary artery disease and its complications, such as
      myocardial infarction and other degenerative disorders, remains low, but the
      situation is rapidly changing, especially in urban areas where appropriate
      diagnostic capabilities exist. It is thought that changes or modifications in
      lifestyle, risk-prone behaviour, diet, cultural attitudes and certain other
      consequences of rapid urbanization and demographic tendencies largely explain the
      observed trends.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8303908
TI  - The decline in cardiovascular health in developing countries.

PMID- 8303909
TI  - Assessing the burden of mortality from cardiovascular diseases.
AB  - The present estimate of global mortality caused by cardiovascular diseases is
      accompanied by a considerable degree of uncertainty, which, in so far as
      monitoring their emergence in developing countries is concerned, undoubtedly
      represents one of the major obstacles to effective public health interventions
      for their control. In much of the developing world, vital registration data are
      lacking and it would be unreasonable to expect rapid progress in the recording of
      causes of death because resources are so limited. The most promising avenue is
      that of the progressive implementation of clearly defined mortality surveillance
      systems that cover all deaths and permit the attribution of probable causes via
      lay reporting. The reliability of the data largely depends on the specificity and
      clarity of the verbal autopsy algorithm employed and on the availability of
      medically trained personnel to validate the returns.

PMID- 8303910
TI  - Cardiovascular diseases in the eastern Mediterranean region.
AB  - Rapid socioeconomic development, urbanization and improved survival have given
      rise to a progressive increase in the occurrence of noncommunicable diseases in
      the Eastern Mediterranean Region. Cardiovascular diseases have emerged as a
      leading cause of morbidity and mortality in many countries. The prevalence of
      hypertension is already high in many countries of the Region and the number of
      hypertensives is likely to increase further in the coming years. Although the
      influence of geographical, ethnic and socioeconomic factors has not been studied
      adequately, it seems that the epidemiological and clinical patterns of
      hypertension do not differ markedly from those in developed countries. The
      growing impact of cardiovascular disease is already understood in most countries.
      The human and economic costs are enormous, there is a growing demand for medical
      services, and the need to take action is increasingly acknowledged. Most
      countries have either initiated or indicated the need to establish programmes in
      collaboration with WHO on the prevention and control of cardiovascular disease
      during 1992 and 1993. In view of the scarcity of precise epidemiological
      information, data collection and the assessment of risk factors for coronary
      heart disease are expected to form the basis of preliminary activities.

PMID- 8303911
TI  - Alpha omega alpha election and medical school thesis publication: relationship to
      subsequent publication rate over a twenty-year period.
AB  - To determine the importance of academic and research success during medical
      school upon subsequent academic activity, a computerized literature search was
      performed using the names of the 79 surviving members of the Yale Medical School
      Class of 1970. Individuals elected to Alpha Omega Alpha (AOA) during the third
      year of school had significantly more publications (mean 101.7 +/- 69.6) between
      1970 and 1990 than those elected during the fourth year (mean 28.3 +/- 48.0, p =
      0.01). Both had significantly more publications than non-AOA members (mean 11.1
      +/- 19.4, p = 0.02). Publication of the student's medical school thesis was also
      associated with a greater number of publications than thesis non-publication
      (mean 22.1 +/- 37.5 vs 14.4 +/- 30.0, p = 0.005). These studies demonstrate that,
      at least at the institution studied, election to AOA and publication of the
      results of a research project were associated with increased publication rates in
      the medical field over the 20-year period following medical school graduation.

PMID- 8303913
TI  - The Department of Obstetrics and Gynecology at Yale: the first one hundred fifty
      years, from Nathan Smith to Lee Buxton.
AB  - The persons who directed the academic teaching of women's health at Yale Medical
      School are presented by biographical sketches recounting their achievements and
      some of the difficulties they encountered. Three who provided particular
      catalysis were Nathan Smith, Herbert Thoms, and Lee Buxton.

PMID- 8303914
TI  - [16th Symposium for Attorneys and Physicians. 22-23 January 1993. Legal and
      medical problems at the beginning of life].

PMID- 8303915
TI  - [When human life begins from the medical viewpoint].

PMID- 8303912
TI  - Cocaine effects on neonatal heart rate dynamics: preliminary findings and
      methodological problems.
AB  - Cocaine use by pregnant women has been reported to cause fetal and neonatal
      morbidity and mortality. We hypothesized that human neonates exposed to cocaine
      via maternal use during pregnancy might manifest changes in beat-to-beat heart
      rate variability, similar to those described in experimental animals. In this
      preliminary report, we present findings from the first systematic analysis of
      heart rate dynamics in a small group of (n = 5) neonates exposed in utero to
      cocaine compared to gestationally age matched controls (n = 6) without known drug
      exposure. Overall heart rate spectral power during ten minute periods of
      quiescent sleep was significantly reduced (p < 0.01) in the cocaine-exposed
      group, reminiscent of the changes recently reported in an animal model. In two
      other cocaine-exposed newborns, a quiescent sleep period could not be found. We
      discuss the special methodological problems associated with collection and
      interpretation of such data.

PMID- 8303916
TI  - [When does human life begin from the bioethical viewpoint?].

PMID- 8303917
TI  - [Ethical problems at the beginning of human life].

PMID- 8303918
TI  - [When does human life begin? Legal considerations].

PMID- 8303919
TI  - [Intentions and effects of the embryo protection regulation from the legal
      viewpoint: goals of the embryo protection regulation].

PMID- 8303920
TI  - [Intentions and effects of the embryo protection regulation from the physician's
      viewpoint].

PMID- 8303921
TI  - [Intentions and effects of the embryo protection regulation--sequelae for the
      public health service physician].

PMID- 8303922
TI  - [Research with human embryos: the scientific and legal status in countries
      outside of Germany].

PMID- 8303923
TI  - [Theoretical medical considerations with reference to fetal and maternal rights
      in pregnancy termination].

PMID- 8303924
TI  - [Pregnancy termination for so-called "fetal" indications].

PMID- 8303925
TI  - [Fetocide in multiple pregnancy].

PMID- 8303926
TI  - [Survival of the fetus in maternal brain death].

PMID- 8303927
TI  - [Rights of the embryo/rights of the mother in the embryonal and fetal phase from
      the legal viewpoint].

PMID- 8303928
TI  - [Responsibility to treat premature and newborn infants from the obstetric
      viewpoint].

PMID- 8303929
TI  - [Limits of responsibility to treat premature and newborn infants].

PMID- 8303930
TI  - [Responsibility to treat premature and newborn infants from the pediatric surgery
      viewpoint].

PMID- 8303931
TI  - [Responsibility to treat premature and newborn infants from the legal viewpoint].

PMID- 8303932
TI  - [Organ donation of moribund newborn infants from the viewpoint of transplantation
      surgery].

PMID- 8303933
TI  - [Organ donation of moribund newborn infants--from the legal viewpoint].

PMID- 8303934
TI  - ["Methods for harmonizing legal rights"].

PMID- 8303935
TI  - Production and in vivo use of recombinant ovine IL-1 beta as an immunological
      adjuvant.
AB  - To determine the potential of ovine interleukin 1 (IL-1) as a vaccine adjuvant in
      sheep, we have expressed and purified recombinant ovine IL-1 beta (rovIL-1 beta)
      from bacterial cultures using a modified form of the ovine IL-1 beta cDNA.
      Adjuvant trials using the model protein avidin demonstrated that rovIL-1 beta
      when administered in association with a compound providing a slow-release
      mechanism, resulted in significant enhancement of specific serum antibody levels
      in both mice and sheep. In a dose-response experiment in sheep, intradermal
      immunization with avidin plus either 10 or 100 micrograms of rovIL-1 beta in
      aluminium hydroxide resulted in antibody levels four- to eightfold higher than
      immunizations without rovIL-1 beta. The addition of rovIL-1 beta also resulted in
      a more severe DTH response to avidin indicating that rovIL-1 beta is able to
      enhance both humoral and cell-mediated responses to avidin. The highest antibody
      titres were observed when sheep received rovIL-1 beta in both the primary and
      secondary immunizations although the addition of rovIL-1 beta in only one of the
      immunizations still resulted in a significant increase in antibody levels.
      Additional experiments showed that rovIL-1 beta and avidin must be administered
      in a site drained by the same lymph node for the adjuvant effect of rovIL-1 beta
      to be observed.

PMID- 8303936
TI  - Interference between cold-adapted (ca) influenza A and B vaccine reassortants or
      between ca reassortants and wild-type strains in eggs and mice.
AB  - Interference between pairs of cold-adapted (ca) influenza A and B vaccine
      reassortant viruses and between ca influenza B reassortant viruses and wild-type
      influenza strain A/PR/8/34 was studied in embryonated eggs and/or in the
      respiratory tract of three strains of mice. Interference in eggs between ca A and
      B reassortants occurred after 2 days but was masked by later cycles of growth.
      When doses of 10(6) EID50 of the reassortant viruses B/60/32/R and A/47/6/R were
      administered to outbred mice, interference with the growth of A/47/6/R occurred
      in the turbinates; interference with the growth of B/60/32/R did not occur.
      However, interference with the growth of B/60/32/R was noted in the lungs of
      Balb/c mice after co-infection with 10(6) EID50 of both A/PR/8/34 and B/60/32/R.
      Interference did not occur when the dose of B/60/32/R was increased to 10(7)
      EID50 per mouse. When CBA mice were co-infected with 10(6) EID50 of both
      B/60/32/R and the influenza A ca reassortant R/34, or 10(6) EID50 of
      B/60/32/R,R/34 and A/Leningrad/134/57, interference did not occur. Interference
      could not be detected in mice following dual infection from serum responses to
      individual viruses.

PMID- 8303937
TI  - Acellular pertussis vaccines in infants: evaluation of single component and two
      component products.
AB  - Two acellular pertussis vaccines, one containing only LPF toxoid (25 micrograms)
      and the other containing LPF toxoid (25 micrograms) and FHA (25 micrograms) and
      each combined with diphtheria and tetanus toxoids, were evaluated in two groups
      of 25 infants. A third group of 25 infants served as controls and received a DTP
      whole-cell pertussis vaccine. Infants given either acellular pertussis vaccine
      had significantly fewer local and systemic reactions than infants given whole
      cell vaccine. Among the three vaccine groups, infants given the LPF vaccine
      (single component) had the highest concentration of antibody to LPF after three
      immunizations. Infants receiving the LPF/FHA vaccine (two-component) had the
      highest concentration of antibody to FHA after three immunizations. Infants
      vaccinated with the two-component vaccine had a significantly lower serological
      response to LPF than infants given the single component vaccine, as measured by
      either enzyme-linked immunosorbent assay or CHO cell assay. Further studies are
      necessary to determine why differences in immunogenicity of the two
      investigational vaccines occurred.

PMID- 8303938
TI  - Immunogenicity and antigenicity of a Plasmodium falciparum protein fraction (90
      110 kDa) able to protect squirrel monkeys against asexual blood stages.
AB  - A monkey vaccination trial using a Plasmodium falciparum protein fraction
      containing antigens of 90-110 kDa is reported. The fraction was obtained by
      electroelution from preparative polyacrylamide gels. Three monkeys out of five
      resisted a heavy challenge dose of highly virulent parasites. Using specific
      antisera, several components of the fraction were identified, namely heat shock
      protein 90 (hsp90), Ag44/RhopH3, ABRA, 96tR/GBP130 and Pf96 protease. The
      fraction did not contain KAHRP, nor the SERP antigen. The antibody response of
      the monkeys was studied on these individual antigens purified by preparative
      immunoprecipitation. Surprisingly, hsp90 was found in the immunoprecipitates
      obtained with SERP antisera. Interestingly, the response to hsp90 correlated with
      protection, high antibody titres being found only in the protected monkeys. In
      contrast, no correlation with protection could be found for the response to the
      other antigens.

PMID- 8303939
TI  - Long-term follow-up study of rubella antibodies in naturally immune and
      vaccinated young adults.
AB  - Selective rubella vaccination of 12-year-old schoolgirls was introduced in Sweden
      in 1973 and at the same time a long-term follow-up cohort study was initiated. In
      1982, a two-dose programme with a combined vaccine against measles, mumps and
      rubella (MMR) was introduced and vaccinations were given at the ages of 18 months
      and 12 years to both boys and girls. The cohort initially comprised 486 girls. It
      was followed for between 8 and 16 years. All the girls enrolled were seronegative
      before vaccination and had seroconverted to a haemagglutination-inhibition (HAI)
      titre of at least 1:16. On the last test occasion 16 years later, 22% had titre
      values below 1:16, and 6% lacked detectable antibodies against rubella (< 1:8). A
      fourfold or greater rise in titre was seen in 36% of the girls during the first 8
      years of observation, whereas during the following 8 years only 1% showed a
      significant increase of titre values. The geometric mean titre declined from
      1:110 to 1:34 during the first 8 years and further to 1:18 during the following 8
      years. From 1982 to 1990, the seroimmunity to rubella of 18-year-old girls and
      boys was studied yearly. The number studied was 3308 18-year-old schoolgirls and
      6347 18-year-old recruits born between 1964 and 1972. The recruits were divided
      into two groups, 4610 unvaccinated and born in 1964-1969 and 1737 vaccinated and
      born in 1970-1972. Seropositive recruits in the first group were thus naturally
      immune only, while the second group had a mixture of natural and vaccine-induced
      immunity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8303940
TI  - Primary in vitro sensitization of human T-helper lymphocytes by peptides derived
      from the V3 loop of human immunodeficiency virus type 1 (HIV-1) envelope
      glycoprotein.
AB  - To generate CD4+ T-helper cell lines, lymphocytes from HIV-seronegative subjects
      were primed in vitro with peptides derived from the V3 loop of HIV-1 gp120.
      Antigen-specific reactivity was inhibited by an anti-DR monoclonal antibody,
      indicating HLA-class II dependency, but peptides could be recognized in different
      HLA-class II contexts. Three sites on V3LAI and two on V3MN were identified as
      targets of the respective V3LAI- and V3MN-specific lines. Recognition of V3
      peptides was isolate-specific. The lines did not react against whole gp160, which
      suggests that V3 may be differently presented when used as such rather than as
      part of the entire glycoprotein. Similar results were obtained in chimpanzees
      immunized in vivo against V3LAI.

PMID- 8303941
TI  - Potential of polymer microencapsulation technology for vaccine innovation.
AB  - Biodegradable polymer microspheres or microcapsules developed over the past
      decade for reliable, preprogrammed release of contraceptive steroids have
      significant potential for adaptation to antigen release for immunization. In
      addition, polymeric encapsulation of antigens could prevent the acid and
      enzymatic degradation that has been a barrier to the development of oral
      vaccines. This review summarizes the published experience with microencapsulated
      hormones and antigens, describes the process of microsphere production, discusses
      the strengths and weaknesses of this approach to immunization, and outlines the
      gaps in knowledge. Microsphere technology has the potential benefits of reducing
      the number of inoculations, enhancing the immune response via both parenteral and
      oral vaccination routes, and in reducing the total antigen dose required to
      achieve immune protection.

PMID- 8303942
TI  - Expression of the merozoite surface protein gp195 in vaccinia virus.
AB  - The DNA sequence coding for the merozoite protein gp195 was inserted into the
      vaccinia virus expression plasmid pvHAX31. This recombinant plasmid was used to
      integrate the gp195 DNA into the vaccinia virus genome by homologous
      recombination. The resulting chimeric virus was tested for gp195 expression in CV
      1 cells by Western blotting. The virus that gave positive results was then grown
      on a large scale and used to infect rabbits. The animal antibody response towards
      gp195 was analysed in detail. The possibility of using gp195 as a component in a
      multivalent malaria vaccine is discussed.

PMID- 8303943
TI  - Characterization of the circulating T-cell response after oral immunization of
      human volunteers with cholera toxin B subunit.
AB  - The kinetics and phenotypic characterization of the in vitro cell proliferative
      response to the B subunit of cholera toxin were studied using peripheral blood
      mononuclear cells taken from human volunteers at frequent time points after
      primary and booster oral immunizations. The cells induced to proliferate by oral
      immunization secreted IL-3, and lipopolysaccharide depletion and depletion of B
      cells did not affect proliferation. Flow cytometry demonstrated that activated
      cells were CD3- and CD4-positive. These findings indicate primed T cells
      proliferating specifically to the B subunit. The kinetics of the response
      suggested trafficking in the peripheral circulation of primed T cells from the
      gut, with a peak stimulation index of between 7 and 93 after first immunization,
      and a precursor frequency of primed cells of between 1 in 25,400 and 1 in 72,390.
      There was close correlation between the serum antitoxin IgA antibody levels and
      observed proliferation.

PMID- 8303944
TI  - Vaccination with immunodominant peptides encapsulated in Quil A-containing
      liposomes induces peptide-specific primary CD8+ cytotoxic T cells.
AB  - Immunostimulating complexes (ISCOMs), containing lipids, the saponin Quil A, and
      proteinaceous antigens, have been proven to vaccinate effectively CD8+ cytolytic
      T cells in vivo. However, conventional ISCOM technology is restricted to
      hydrophobic proteins or fatty acid-derivatized proteins or peptides. We therefore
      analysed whether Quil A-containing liposomes are an effective vehicle to shuttle
      hydrophilic proteins or peptides into the MHC class I pathway of antigen
      presentation resulting in the in vivo induction of antigen-specific cytolytic T
      cells (CTL). Liposomes were formed by a lipid dry-down method followed by
      resuspension with an aqueous solution containing protein/peptide and Quil A and
      then an extrusion step. Quil A-containing liposomes are an effective means to
      elicit a CD8+ CTL response to peptide antigen in vivo. CTL could be raised in
      C57B1/6 mice against ovalbumin (OVA) peptide 257-264 and vesicular stomatitis
      virus nucleoprotein 52-59, as well as in Balb/c mice against listeriolysin
      peptide 91-99 and cytomegalovirus pp89 168-176, demonstrating the versatility of
      this approach. The elicited response was peptide-specific, peptide dose-dependent
      and Quil A was necessary. Vaccination with liposomes entrapping the whole
      ovalbumin molecule or an extended (OVA) peptide 254-276 also yielded a CTL
      responsive to the immunodominant OVA peptide 256-264, implying cellular
      internalization and correct processing. Thus Quil A-containing liposomes appear
      to be a versatile vehicle to vaccinate CD8+ T cells in vivo; in addition, they
      could rapidly enhance the understanding of subunit vaccines and rules of antigen
      processing and peptide-MHC class I binding.

PMID- 8303945
TI  - Comparative study of Lederle/Takeda acellular and Lederle whole-cell pertussis
      component diphtheria-tetanus-pertussis vaccines in infants in Germany.
AB  - In preparation for a large efficacy trial in Germany, a pilot study was initiated
      in December 1990. In this study 149 infants were enrolled; with double-blind
      randomization 75 received Lederle/Takeda acellular pertussis component diphtheria
      tetanus-pertussis vaccine (APDT) and 74 received Lederle whole-cell pertussis
      component diphtheria-tetanus-pertussis vaccine (DTP). The mean age at first dose
      was 3.5 months, and the second and third doses followed at 6-week intervals.
      Reactions were relatively mild with both vaccines; in general they were less
      frequent following APDT. The IgG antibody responses to lymphocytosis promoting
      factor (LPF) and fimbriae-2 were similar in both groups whereas the responses to
      pertactin and filamentous haemagglutinin (FHA) were greater in APDT recipients.
      DTP recipients had greater responses to tetanus and diphtheria toxoids. When age
      of first dose was examined (8-12 weeks versus 16-20 weeks), it was found that
      young age had a suppressive effect on antibody responses in DTP but not APDT
      recipients to LPF toxoid, pertactin, fimbriae-2, and tetanus and diphtheria
      toxoids. High values of transplacentally acquired antibody lessened the response
      to LPF toxoid and tetanus toxoid in DTP recipients and to tetanus toxoid in APDT
      vaccinees. The IgG immune response to LPF toxoid, FHA and fimbriae-2 was found to
      be more uniform in APDT recipients than in DTP vaccinees. An IgA antibody
      response to fimbriae-2 was noted in 13% of DTP recipients but in no APDT
      vaccinees. The broad immunogenicity and mild reactogenicity of this APDT vaccine
      justifies its use in the German efficacy trial.

PMID- 8303947
TI  - The International Community of Yeast genetics and Molecular Biology. Directory.

PMID- 8303946
TI  - Immunization of hospital personnel with low-dose intradermal hepatitis B vaccine.
AB  - Hepatitis B (HB) is an occupational hazard among health care workers. The only
      hope of control is by the use of vaccines. We evaluated the efficacy of HB
      vaccine, given intradermally to 304 hospital staff members. Two plasma-derived
      vaccines were used (Merck, Sharpe & Dohme (MSD), USA; Cheil Sugar & Co., South
      Korea). Both vaccines gave comparable, satisfactory results, the MSD vaccine
      inducing anti-HBs in 83% of those vaccinated and Cheil Sugar vaccine inducing
      anti-HBs in 86%. More than 50% developed anti-HBs titres in excess of 1000 mIU ml
      1. The vaccines were well tolerated and there were no serious side effects. A
      good immune response was found when the vaccine was comparatively fresh but there
      was tapering of response when the vaccine neared the expiry date. The 0.1 ml dose
      by the intradermal route is safe, cost-effective and suitable for immunization of
      health care workers in developing countries such as India.

PMID- 8303948
TI  - Analysis of sensory and physicochemical data on commercial tomato puree with
      pattern recognition techniques.
AB  - The correlations between analytical parameters and some typical sensory
      attributes of commercial tomato puree (8-14 degrees Brix) were studied. In order
      to ensure the widest possible variance multivariate analyses was used. A model
      was obtained that could describe the different contribution of the analytical
      variables to the sensory attributes examined. Cluster analysis revealed the
      existence of two distinct sub-groups; traditional by tomato puree and organically
      produced tomato puree.

PMID- 8303949
TI  - Ascorbic acid and dehydroascorbic acid content of blanched sweet green pepper
      during chilled storage in modified atmospheres.
AB  - Sweet green pepper (Capsicum annuum L.) cut into pieces was analysed for ascorbic
      acid (AA) and dehydroascorbic acid (DHAA) content before and after blanching,
      after 1, 4 and 7 days of chilled storage in modified atmosphere, and after
      reheating. No difference in retention of AA was noted between storage in 2 and 4%
      O2 atmospheres, whereas retention during storage in air was significantly lower.
      Production of DHAA during storage increased with increased O2 content in the
      atmosphere. After 7 days of storage, DHAA contributed 10-35% of the total AA, and
      DHAA contributed 12-25% after reheating, depending on the O2 content in the
      atmosphere. Since the vitamin activity of DHAA is considered to be the same as
      that of AA, it is concluded that the content of DHAA in processed green pepper is
      of importance and should be measured together with AA.

PMID- 8303950
TI  - Determination of PCBs in fatty tissues by means of several detection techniques.
AB  - Difficulties with harmonization of analytical procedures and consequently poor
      comparability of generated data represent in the Czech Republic the main reason
      for the delay in issuing of updated legislation for polychlorobiphenyls (PCBs) in
      foodstuffs. This study draws attention to possible errors (overestimations) that
      can occur during routine determination of these residues in the fat portion of
      biotic matrices. We demonstrate the gas chromatographic (GC) conditions under
      which interfering contaminants such as phthalates and/or chlorinated pesticides
      can be separated from analytes. Discussion is focused on the advantages and
      drawbacks of GC with an electron capture detector, GC mass spectrometry and GC
      with an atomic emission detector. Various approaches used for calculation of PCBs
      contents are compared.

PMID- 8303951
TI  - [Arsenic, lead and cadmium in the customary homemade fruit and vegetable
      preserves from earlier decades. 1. Cherries from the harvest year 1911 on].
AB  - Levels of arsenic, lead and cadmium in cherries of harvest years 1911 to 1986,
      home-sterilized in glass jars, were determined by atomic absorption spectrometry.
      Concentrations of arsenic showed a decreasing trend during that period,
      presumably reflecting the discontinuation of the use of arsenic-containing
      pesticides. Unexpectedly, some of the older samples also contained more lead or
      more cadmium than more recent samples.

PMID- 8303952
TI  - [Determination of the folic acid content of grain, cereal products, baked goods
      and legumes using high-performance liquid chromatography (HPLC)].
AB  - The folic acid content of grain, cereal products (including beer), bakery
      products and legumes was determined by means of high-performance liquid
      chromatography (HPLC). Free folate (monoglutamate forms) and total folate
      (monoglutamate + polyglutamate forms) were differentiated. Of the grain analysed,
      rye, with a mean value of 143 micrograms/100 g, contained more total folate than
      wheat (mean = 91 micrograms/100 g). The total folate content of bakery products
      ranged from 14 micrograms/100 g (whole grain rye bread) to 88 micrograms/100 g
      (crispbread). Beer had a very low total folate content (mean = 3 micrograms/100
      ml). The mean of the free folate portion was 76.5% in grain and cereal products
      and 65.6% in bakery products. Of the legumes analysed, beans (mean = 128
      micrograms/100 g) had the highest content of total folate, followed by lentils
      (103 micrograms/100 g) and peas (57 micrograms/100 g). The mean value of the free
      folate portion in legumes (73.1%) was comparable with the values of grain, cereal
      products and bakery products. In addition to tetrahydrofolic acid (THF), 5-methyl
      THF and 5-formyl-THF, pteroylglutamic acid (PteGlu) and 10-formyl-PteGlu were
      determined in all products (except beer). Their proportion (PteGlu + 10-formyl
      PteGlu) of the total folate content ranged from 23.5% to 44.4%.

PMID- 8303953
TI  - Mucor thermophilus spec. nov. and other Mucorales from India.
AB  - Ninety-five isolates belonging to the order Mucorales were collected from the
      vicinity of Delhi. These were derived as pure sporulating forms from various
      substances viz., dung, soil and compost. In all, twenty-one different species of
      Absidia, Cunninghamella, Mucor and Rhizopus were identified with the help of
      available literature (Hesseltine and Ellis 1964, 1966, Inui et al. 1965, Schipper
      1978, 1984, Baijal and Mehrotra 1980 and Schipper and Stalpers 1984). Out of
      these, five fungi were new to India. A new species of Mucor and Rhizopus
      microsporus var. pseudochinensis comb. nov. is described.

PMID- 8303954
TI  - Inhibitory effect of spice oils on lipase and mycotoxin production.
AB  - Five spice oils were tested for their inhibitory activity towards the growth,
      respiration, lipase and mycotoxin productions by Aspergillus parasiticus var.
      globosus IMI 120920 and A. fumigatus. Cumin, onion, garlic and clove oils
      completely inhibited sterigmatocystin production. Cumin, onion and clove oils
      significantly suppressed aflatoxin production. Most of tested oils exhibited
      considerable inhibition on mycelial growth. Incorporation of these oils in basal
      medium suppressed lipase production with variable degrees. Onion oil was the most
      effective one. All spice oils significantly reduced or completely suppressed CO2
      evolution of A. fumigatus, whereas CO2 evolution of A. parasiticus was slightly
      enhanced by these oils except with cumin and clove. Our results suggest that the
      use of spice oils may offer some advantage in the prevention of mycotoxin
      production.

PMID- 8303955
TI  - Effect of four pesticides on aflatoxin production by Aspergillus flavus IMI
      89717.
AB  - The effect of three fungicides (Vitavax-Captan, Rizolex-T and Sumisclex) and one
      insecticide (Actellic), when incorporated into liquid medium or applied to corn
      grains and sunflower seeds, on the production of aflatoxin by A. flavus IMI 89717
      was tested. In liquid medium, aflatoxin production was inhibited by 27%, 82%,
      100% and 100% when Vitavax-Captan was added at 10, 25, 50 and 100 ppm,
      respectively. Sumisclex reduced to some extent the production of total aflatoxin,
      while Rizolex-T and Actellic did not affect quantitatively the mycotoxin
      production. Rizolex-T proved to be the most effective pesticides tested on
      aflatoxin production on both corn-grains and sunflower seeds, while Vitavax
      Captan was the second most effective pesticide. Both Sumisclex and Actellic did
      not inhibit aflatoxin production on either corn grains or sunflower seeds at the
      levels tested.

PMID- 8303956
TI  - [Osteomyelitis today--diagnostic imaging and therapy].
AB  - Plain radiography, bone scan and especially in infants sonography belong to the
      primary imaging methods for posttraumatic osteomyelitis. For further diagnostic
      check up of osteomyelitis CT, MRI and leukocyte scintigraphy are excellent
      methods. Treatment of posttraumatic osteomyelitis is today a combination of
      operation, local and systemic antibiotic therapy.

PMID- 8303957
TI  - [Surgical limb lengthening--experiences and results].
AB  - This paper describes the experiences and results in 172 operative lengthening
      procedures on 134 patients, performed in the Orthopaedic Department of Charite
      Hospital in Berlin. The bone length increase was on an average 8.5 cm (min.: 1
      cm, max.: 20 cm), this gives altogether a bone increase of over 14 meters.
      Patients are differentiated in groups of age, indication, localization, mode of
      procedure (callus-distraction, epiphysealdistraction) and in regard to the used
      external fixation devices. Authors present their own model of wire fixed external
      fixateur (so called "Berlin type-external fixateur"), a modification of the
      original Ilizarov-device. Importance of procedure-planning and time-balance as
      well as the high rates of complications (146 complications = 84.8%) are
      discussed.

PMID- 8303958
TI  - [Surgical treatment of trochanteric femoral fractures with G. Kuntscher Y
      nailing].
AB  - For the treatment of trochanteric fractures different osteosynthetic devices are
      available. One of these is Kuntscher's y-nail, which has been already developed
      in 1939, but is nowadays rarely used. We have evaluated data on 632 patients,
      treated between 1975 and 1985 with this method. In this high aged (78 years
      average) multimorbid group of patients the postoperative mortality reached 20.9%.
      Complications of osteosynthesis appeared only in 5.8%, poor functional results
      were noticed in even less than 1%. The full weight stability immediately after
      the operation independently from the type of fracture was considered as a main
      advantage of the method. Compared to other osteosynthetic devices the y-nailing
      represents an at least equivalent method, which is able to stabilize all types of
      trochanteric fractures of the elderly people with simple technique and good
      results.

PMID- 8303960
TI  - [Angiodysplasia of the intestine--rational diagnosis and therapy].
AB  - Vascular ectasias of the gastrointestinal tract are local changes in the
      development of blood vessels, frequently associated with an arteriovenous shunt.
      The reported rates of such angiodysplasias have been increased in the past years
      due to improved diagnostic procedures as well as a general increase in the age of
      the population. The majority of these changes is found in the right colon. It is
      often difficult to localize the bleeding. We treat our patients according to the
      following diagnostic regimen: esophagogastroduodenoscopy, proctorectoscopy,
      colonoscopy, angiography, erythrocyte scintigram and diagnostic laparotomy.
      Therapeutic approaches include the surgical resection of the bleeding area as
      well as interventional endoscopy. To further reduce the high mortality rate
      associated with this disease, an early diagnosis and treatment are essential.

PMID- 8303959
TI  - [Peripheral neurogenic tumors--surgical therapy of nerve sheath tumors. Review
      and personal results].
AB  - Nerve sheath tumors are rare tumors originating from the Schwann's cover cells.
      Neurinomas, neurofibromas and schwannomas can be separated due to a diverse
      growth behavior. 24 patients with neurinomas and 13 patients with neurofibromas
      were operated on from January 1, 1987 to December 31, 1992 at the Department of
      Surgery, University Cologne. A total of 10 patients received treatment during the
      last ten years because of schwannoma. The concepts of treatment and
      differentiation of the various tumors are demonstrated and compared based on the
      patients records and on a review of the literature.

PMID- 8303961
TI  - [Primary hyperparathyroidism in intrathyroid parathyroid cancer].
AB  - Parathyroid carcinoma is a rare cause of hyperparathyroidism. Histological
      differentiation from parathyroid adenoma may be difficult and is rarely achieved
      intraoperatively. Parathyroid carcinomas are sometimes localized heterotopically.
      We report a case of parathyroid cancer in the left thyroid lobe. Surgical therapy
      should include en bloc resection of the tumor, the thyroid lobe and the
      parathyroid tissue.

PMID- 8303962
TI  - [Initial experience with the NOVACOR left heart assist system in transition for
      heart transplantation at the Grosshadern Clinic].
AB  - We recently used an electrically powered left ventricular assist device (NOVACOR
      Corp., Oakland, Calif.) to support the circulation of a 17-year-old man with
      profound circulatory impairment. He had been regularly listed for cardiac
      transplantation previously because of dilated cardiomyopathy, and decompensated
      acutely with severe biventricular failure before a suitable donor heart became
      available. Isolated left ventricular support with the NOVACOR system provided
      adequate haemodynamics and recovery of right ventricular, hepatic and renal
      function. After 2 days of support, orthotopic heart transplantation could be
      performed successfully. Five days after transplantation he developed a massive
      cerebral haemorrhage during a hypertensive crisis of which he recovered
      completely after neurosurgery without any residuals. He ist currently doing
      extremely well some 14 months after transplantation.

PMID- 8303963
TI  - Role of leukocytes in the initial hepatic microvascular response to endotoxemia.
AB  - INTRODUCTION: Accumulation and adherence of leukocytes within the hepatic
      microvasculature have been emphasized to play a major role in the pathogenesis of
      endotoxin/lipopolysaccharide (LPS)-induced liver injury. However, there is no
      information on their interrelation with hepatic microvascular perfusion failure,
      hepatocellular damage and liver dysfunction following LPS exposure. AIM AND
      METHODS: Therefore, we quantitatively assessed the initial LPS-induced hepatic
      microvascular response, including leukocyte-endothelium interaction and their
      interrelation with sinusoidal perfusion, hepatocellular integrity (serum AST/ALT
      activity) and excretory function (bile flow). After infusion of LPS (E. coli
      0128:B12; 10 mg.kg-1 i.v.) intravital fluorescence microscopy was applied to
      livers of Sprague-Dawley rats. RESULTS: 1 h after LPS exposure deterioration of
      hepatic microcirculation was hallmarked by significant accumulation of
      leukocytes, stagnant within sinusoids and adherent to the endothelial lining of
      postsinusoidal venules. This was accompanied by a progressive increase of the
      number of non-perfused sinusoids (20 +/- 4%). During the 1 h period after LPS
      exposure, bile flow was found significantly (p < 0.05) reduced, while serum
      AST/ALT activities remained unchanged. Leukocytes appear to contribute to
      sinusoidal perfusion failure, since the number of non-perfused sinusoids
      significantly (p < 0.01) correlated with the number of leukocytes stagnant within
      the sinusoids. In addition, the inverse correlation (p < 0.01) of bile flow with
      the number of both, leukocytes stagnant within the sinusoids and non-perfused
      sinusoids indicates that microvascular injury initiates hepatic dysfunction.
      CONCLUSION: Inasmuch as LPS exposure initially induces only microcirculatory
      disturbances without substantial loss of hepatocellular integrity, we propose
      that therapeutic strategies during early endotoxemia should focus on attenuation
      of microvascular injury to prevent manifestation of hepatocellular damage.

PMID- 8303964
TI  - [Bio-artificial organ replacement of the liver].

PMID- 8303965
TI  - [Study of the pancreas and its inflammatory diseases from the 16th-19th century].
AB  - The author describes the development of medical research since the 16th century
      based on a literary review of the study of the anatomy, physiology and pathology
      of the pancreas. The anatomical basis was first created in the 17th century when
      the pancreatic duct was discovered (J.C. Wirsung 1642) and the duodenal papilla
      was described (J.K. Brunner 1683, C.B. Holdefreund 1713 and A. Vater 1750). The
      physiological function of the pancreas as a secretary gland was first
      experimentally investigated by R. Graaf (1671). A few decades later the enzymatic
      breakdown of nutrients by pancreatic juice was demonstrated in animal experiments
      (G. Valentin 1844, Cl. Bernard 1849). The earliest case reports of patients dying
      of suppurative inflammation or tumours of the pancreas were presented by S.
      Alberti (1578), J. Schenck (1600), and N. Tulp (1641). The presence of fatty
      necrosis in acute pancreatitis was first indicated by W. Balser (1882), and the
      autodigestive genesis was suspected by H. Chiari (1896). The discovery in the
      19th century that diabetes mellitus occurs in dogs following total pancreatectomy
      (J. von Mering and O. Minkowski 1890) and the first operation on a pancreatic
      cyst by "marsupialisation" (C. Gussenbauer 1883) as well as the emergence of the
      connection between cholelithiasis and acute pancreatitis (E.L. Opie and W. St.
      Halsted 1901) laid the foundation for 20th century research.

PMID- 8303966
TI  - On a mathematical theory of embolism.
AB  - A theory of embolism based on an optimization model of blood flow is proposed and
      used to explain the topographic distribution of emboli in arterial trees.

PMID- 8303967
TI  - Biological individuality and disease. From Garrod's Chemical Individuality to HLA
      associated diseases.
AB  - The concept of "predisposition" in medicine is ancient, and the term "diathesis"
      was used to express it since the days of Hippocrates and, especially, of Galen.
      The concept of diathesis was enormously popular throughout the nineteenth
      century, despite the vagueness of its actual meaning. It was clarified only in
      the early years of the twentieth century (1902), when it was however losing its
      clinical relevance, by a replacement of the concept of chemical individuality by
      A.E. Garrod, followed thirty years later by the concept of inborn factors in
      disease (1931). "Molecular" knowledge of the biological individuality of human
      beings, highlighted particularly by the discovery of the MHC (Major
      Histocompatibility Complex) during the last 30-35 years, and substantially HLA
      (Human Leukocyte Antigens), has offered a new and better understanding of the
      relationship between the self and the not-self, as well as of various diseases,
      especially if they are favored by some immune dyshomeostatis. Extensive knowledge
      of transplants--their "immune" fate of take or rejection, possibly of GVHD--have
      allowed mankind to consider each human being as a biological Ego, unique in his
      antigenic-molecular structure. But most of all, the demonstration of the fact
      that certain HLA antigens can be significantly associated with a greater
      predisposition, on the part of individuals bearing these antigens, toward
      contracting certain diseases, reconsiders in precise molecular terms the concept
      of "predisposition" and therefore, perhaps, in a new light, even the concept of
      "diathesis", providing an actual logical basis for it.

PMID- 8303968
TI  - Evaluation of the importance of Chlamydia T. and/or Mycoplasma H. and/or
      Ureaplasma U. genital infections and of antisperm antibodies in couples affected
      by muco-semen incompatibility and in couples with unexplained infertility.
AB  - Both the male and female partners of 28 couples with muco-semen incompatibility
      and of 8 couples with unexplained infertility were examined for the presence of
      genital infections by Chlamydia T. and/or Mycoplasma H. and/or Ureaplasma U. (CMU
      infections), and for topical and serum antisperm antibodies (AS-abs). The
      presence of other common genital infections, and for Candida A. and Trichomonas
      had previously been excluded in all the subjects; all the female partners
      presented normal hysterosalpingographs, regular ovulatory function and cervical
      score > or = 10. The main cause of the muco-semen incompatibility was dysspermia
      (35.7%), either associated or not with male CMU infections, followed by female
      CMU infections (21.4%), male CMU infections without dysspermia (3.6%), and the
      presence of AS-abs in the mucus (3.6%) and in the semen (3.6%); in 32.6% of the
      cases no plausible explanation was found for muco-semen incompatibility. In 42.8%
      CMU infections were implicated in the muco-semen incompatibility; furthermore,
      there was associated dysspermia in 50% of the cases. AS-abs were found in the
      mucus or in the serum of 70% of the patients with CMU infections, while this
      figure went down to 34.6% in subjects not affected by such infections. None of
      the patients with CMU infections showed AS-abs either in the semen and/or in the
      serum. AS-abs were found in the serum of 25% of the female patients with so
      called "unexplained" infertility. CMU infections are important for the
      determination of muco-semen incompatibility, both with and without
      dyspermia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8303969
TI  - Purified FSH as a treatment for a cervical hostility.
AB  - Abnormal cervical mucus (CM) quality and quantity is considered one of the causes
      of infertility which occurs in only 2 to 8 per cent of infertile couples. The
      periovulatory mucus with its specific properties is necessary to determine a
      correct Post Coital Test (PCT). Twenty patients, with infertility for over 18
      months and with a baseline negative PCT (repeated at least three times) for
      abnormal CM, were treated with pFSH. Our results show that the pFSH improves the
      quality and quantity of CM in all for our patients including an improvement of
      penetration and motility spermatozoa in 55 per cent of our cases. Therefore we
      suggest the routine pFSH use in case of cervical hostility and recurrent negative
      PCT.

PMID- 8303970
TI  - Exogenous gonadotropin therapy in combined anovulatory and male factor
      infertility.
AB  - This retrospective study evaluated conception rates in 18 women with refractory
      anovulatory infertility undergoing hMG ovulation induction in the presence of
      persistent mild to moderate semen abnormalities. Logistic regression analysis
      showed no relationship between conception (9.6% cycle) and the age of either
      partner, primary versus secondary infertility, or lowest sperm count, motility or
      morphology. In summary, this study demonstrates that a coexisting mild to
      moderate male factor does not preclude pregnancy during hMG therapy for
      anovulation. While semen abnormalities should not be ignored, aggressive
      treatment of concomitant ovulatory disorders and the resulting timed ovulation of
      several oocytes may minimize the effects of semen abnormalities.

PMID- 8303971
TI  - Transcutaneous minoxidil in the treatment of erectile dysfunctions in spinal cord
      injured men.
AB  - We have tested the erectile effect of a topical applied drug (Minoxidil) in 15
      spinal cord injured men. Minoxidil exerts a direct relaxant effect on arterial
      smooth muscles. This topical vasodilatory agent (1 ml of a 2% solution) was
      applied on the skin of the penile shaft. Increases in diameter and rigidity were
      measured with the RigiScan device (Dacomed Minneapolis, Minnesota). A total of 4
      paraplegic men with a complete dorsal level lesion reported a positive erectile
      response. 3 of these 4 patients preferred to continue with this noninvasive
      treatment compared to prostaglandin E1 intracavernous injections. In our study no
      side effects were emerged and minoxidil proved to be well tolerated at the
      cutaneous level of the penis. Our results indicate that this treatment should be
      tested in spinal cord injured men before a invasive therapy is initiated.

PMID- 8303972
TI  - Evaluation of the morphological and functional damage to human sperm subjected to
      freezing at -196 degrees C and to refrigeration at +4 degrees C.
AB  - A study was carried out on five healthy, fertile donors to evaluate refrigeration
      at +4 C compared to cryopreservation at -196 degrees C. These donors had produced
      more than two pregnancies in different women with their cryopreserved semen in an
      AID program. The following parameters for evaluation and comparison were used:
      (i) the percentage of forward sperm motility, (ii) the percentage of swollen
      sperm after hypoosmotic stress (swelling test) and (iii) the sperm morphology
      observed both with a light microscope after staining and with an electron
      microscope. After 48 hours of refrigeration the result obtained were comparable
      with those observed after one week of cryopreservation. After 72 hours of
      refrigeration, a sharp and significant decrease of these values was noted. Our
      data underlined the fact that there is an individual variability in subject
      response to the method of preservation employed. Our findings show the
      possibility of using sperm refrigerated for up to 48 hours in AIH programs.

PMID- 8303973
TI  - Uterine receptivity for egg-implantation and scanning electron microscopy.

PMID- 8303974
TI  - Assisted fertilization with epididymal spermatozoa.
AB  - In vitro fertilization is used for several years as a technique for resolving
      infertility problems due to moderate or severe oligospermia. More recently,
      techniques of micro-insemination of oocytes have also become available for cases
      of extremely severe oligospermia which cannot be resolved by classical I.V.F.
      Nevertheless, although these particular techniques have already led to results
      which have gone far beyond initial hopes, they are not able to resolve all cases
      of male sterility. There are indeed many situations of excretory azoospermia
      associated with normal spermatogenesis; the spermatozoa remain trapped in a more
      or less extensive part of the epididymis because its passage is blocked, either
      because of post-infectious sclerosis, or of agenesis of a variably extensive area
      of the Wolffian duct. Post-inflammatory occlusions can be treated by micro
      surgery, whereas in cases of agenesis, attempts to collect spermatozoa by means
      of an artificial spermatocele have led to far too many failures, and this
      technique has now been abandoned, in spite of some successful pregnancies. The
      extraordinary development of in vitro fertilization techniques has led to the
      logical idea that it might be possible to collect epididymal spermatozoa for
      oocyte fertilization.

PMID- 8303975
TI  - [Mechanism of platelet fibrinogen receptor function and its role in platelet
      hemostasis].

PMID- 8303976
TI  - [Interleukin 2 (IL-2) and its receptor (IL-2R) in healthy individuals and with
      various disease states].
AB  - IL-2 is a cytokine that plays a central role in immune response. It stimulates
      cellular as well as humoral reactivity. The effect of IL-2 depends on the
      interaction with its receptor. Recent reports have documented that high affinity
      interleukin-2 receptors consist of two distinct IL-2 binding proteins, one being
      alpha chain (p55) and the other being IL-2 beta chain (p75). Expression of the
      alpha chain or the beta chain alone allows for low affinity or intermediate
      affinity IL-2 binding, respectively. Alpha receptor is present on activated
      cells, beta chain is present on resting cells. Decreased production of IL-2 and
      decreased expression of IL-2 receptor (IL-2R) after stimulation was found in
      primary and secondary immune deficiencies. Leukemic cells in adult T cell
      leukemia and hairy cell leukemia express markedly large numbers of IL-2
      receptors. Since IL-2 receptors are present on malignant cells but not on normal
      resting cells, clinical trials have been initiated in which patients with adult T
      cell leukemia are treated with monoclonal antibody that binds to IL-2 receptor.

PMID- 8303977
TI  - [Clinical pharmacology of idarubicin].
AB  - Idarubicin (IDA,4-demethoxydaunorubicin) is a new antineoplastic agent that is
      structurally related to daunorubicin (DNR) and has the same mechanism of action
      as DNR and doxorubicin (ADR). Unlike the other currently available
      anthracyclines, IDA has significant oral bioavailability (about 30%). Animal
      tumor studies have shown that it has greater antitumor activity at lower drug
      concentration than DNR. IDA is an effective agent for the management of acute
      myelogenous leukemia (AML). It has achieved greater response rates than the
      standard anthracycline, DNR, when it is administered with cytarabine in newly
      diagnosed patients. IDA is also an effective agent in acute lymphoblastic
      leukemia, lymphomas, breast cancer and some other tumors. Adverse effects are
      similar to those seen with other anthracyclines, although IDA may be associated
      with less cardiotoxicity than ADR or DNR.

PMID- 8303978
TI  - [Effect of human recombinant erythropoietin (rhuEPO) on platelet phospholipids in
      chronically hemodialysed].
AB  - An important role in the formation of haemostasis defects in haemodialysed
      patients play phospholipids. The disturbances of platelet activity play an
      essential part in platelet structure and function. In uraemic patients changed
      plasma lipid pattern is observed, as well as positive influence of human
      recombinant erythropoietin (rhuEPO) on some plasma lipid disorders in these
      patients. The aim of this study was to investigate rhuEPO influence on platelet
      phospholipid composition in haemodialysed patients. RhuEPO was applied
      subcutaneously, 2000j twice a week. Before rhuEPO treatment significant decrease
      of phosphatidylethanolamine (PE), phosphatidylinositol (PI) and
      phosphatidylcholine (PC) contents was observed, as compared with control group.
      After rhuEPO treatment a significant increase of PE and PC contents was noted.
      The obtained results suggest that rhuEPO partially normalizes changed platelet
      phospholipids composition, but detailed mechanism of this influence is unclear.

PMID- 8303979
TI  - [Production of activity stimulating an increase of clonal granulocytic precursors
      by normal B lymphocytes under the influence of various mitogens].
AB  - The effect of mitogen-stimulated (concanavalin A, Con A; phytohemagglutinin, PHA;
      pokeweed mitogen, PWM; Staphylococcus aureus Cowan I, SAC I) normal B lymphocytes
      on the clonal proliferation of granulocytic progenitors from marrow of healthy
      subjects (CFU-dG) was studied in diffusion chamber culture. PWM-, SAC- and Con A
      stimulated B lymphocytes produced an humoral activity that increased the CFU-dG
      derived colony formation. The highest growth-stimulating effect was induced by
      SAC I-preincubated B lymphocytes and to a lesser degree by PWM- or Con A
      stimulated B cells. In contrast, PHA-preincubated and unstimulated B lymphocytes
      revealed no effect on the CFU-dG proliferation.

PMID- 8303980
TI  - [In vitro studies directed at inducing differentiation of leukemic B
      lymphocytes].
AB  - Lipopolysaccharide (LPS) and phorbol esters (TPA) stimulate lymphocytes
      proliferation in two different ways. While LPS primary function is specific
      receptor binding, TPA directly activate cellular protein kinase C. The
      stimulation of human leukaemic lymphocytes (from chronic lymphocytic leukaemia
      patients) with LPS and TPA results in two different types of response: to both
      stimulators, and to LPS only. Therefore the supposed defect of cellular receptors
      can not explain all the observed effects. The existence of TPA independent second
      messengers and changes in signal transduction pathways downstream of PKC can be
      considered.

PMID- 8303981
TI  - [The study of platelet count and phagocytic activity in experimental hemorrhagic
      shock. I. Comparison of platelet count in blood of left and right heart
      ventricles].
AB  - The evaluation of the number of blood platelets in the left and right heart
      ventricle observed during haemorrhagic shock has been carried out. It has been
      stated that the number of blood platelets of the left ventricle outnumber that of
      the right heart ventricle. The difference is more intense with the prolongation
      of the time of the survival in the state of shock.

PMID- 8303982
TI  - [Study of platelet count and phagocytic activity in experimental hemorrhagic
      shock. II. Evaluation of phagocytic activity of platelets].
AB  - The platelets phagocytic activity has been measured in rats during experimental
      haemorrhagic shock determining the per cent of phagocytic platelets and
      phagocytic index. The authors have the decrease of phagocytic activity of
      platelets during haemorrhagic shock. Disturbances of phagocytic activity of
      platelets have been accompanied by changes of their shape and formation platelet
      aggregates.

PMID- 8303983
TI  - [Evaluation of cell cycle in acute leukemias and non-Hodgkin's lymphomas in
      children].
AB  - The DNA profile of blast cells was assayed in 61 children with acute leukemias
      (51 patients) and non-Hodgkins lymphomas (NHL--10 patients). The value of S phase
      (synthesis of DNA) and G2M phase (mitotic stage) was compared between the
      subtypes of acute leukemia and lymphoma based on blast cell phenotype. In acute
      lymphoblastic leukemia (ALL) the lowest S phase of blast cells was seen in null
      ALL subtype, the highest in T-ALL. In non-lymphoblastic leukemia (ANLL) the value
      of S phase was below S phase observed in ALL. B cell NHL showed higher S phase as
      compared to T-lymphocyte derived NHL cells. Aneuploidy was noted as hyperdiploidy
      (8 cases), hypodiploidy (4 cases) and two leukemia cell lines (3 ALL patients).
      The DNA profile as marker of proliferative activity of blastic cells provides an
      important information associated with the prognosis of patient.

PMID- 8303984
TI  - [Evaluation of the microplate enzyme-linked assay with isolation of glycoprotein
      IIb/IIIa from platelet membranes: comparison with immunofluorescent tests and
      monoclonal antibodies].
AB  - The enzyme test with GPIIb/IIIa has been used to detect antibodies in 500 sera
      from patients with thrombocytopenia and mothers of infants with thrombocytopenia.
      The results were compared with antibody detection in the platelet suspension
      immunofluorescence test (PIFT) and in the monoclonal antibody immobilization of
      platelet antigens (MAIPA). Platelet antibodies were detected in 125 sera (25%).
      In 46.2% the results were positive in all three tests. However, in 38.4% the
      ELISA was negative while the PIFT and MAIPA were positive. On the other hand, in
      14.4% the ELISA was positive while the PIFT and/or the MAIPA were negative. The
      ELISA appears to be useful in the detection of anti-HPA-1a antibodies, which are
      the main cause of AIMN and PTP. This test, however, seems to be less useful in
      the detection of autoantibodies. The significance of the ELISA in the detection
      of platelet alloantibodies responsible for refractoriness to platelet
      transfusions is not clear yet and requires further investigations.

PMID- 8303985
TI  - Late relapse after presumed cure of childhood acute lymphoblastic leukemia.

PMID- 8303986
TI  - [Report of the XII-th International Meeting of the Hematologic Society (European
      and African Division)].

PMID- 8303987
TI  - Using a conceptual model for practice in a nursing wellness centre for seniors.
AB  - The use of a conceptual model to guide practice is critical to the maturation of
      the profession. Distinguishing between nursing and other health care professions
      rests, in part, on nursing's ability to articulate what it offers to clients. The
      nursing paradigm, comprising the essential components of the individual (client),
      health, environment, and nursing, provides general rules of thumb for the
      profession (Fawcett, 1984). Selecting a nursing model for a practice setting
      contributes to theory development: clinical questions generated from the model
      can be formulated as testable hypotheses. The Wellness Centre offers a unique
      opportunity for use of a conceptual model in a nurse-managed practice setting
      serving seniors. If conceptual models are to be useful, they need to be tested in
      the settings where nurses practise and for the roles that comprise nursing. Use
      of the crisis model, in this setting provides reality testing of the model which
      has evolved to a higher level of internal consistency and external validity as a
      direct result of practice.

PMID- 8303988
TI  - The patient information board, alias the "pictogram".

PMID- 8303990
TI  - Searching for care solutions: the ill elderly.

PMID- 8303989
TI  - Building a professional image: a caring program for gerontological nurses.

PMID- 8303991
TI  - So you're mad--now what?

PMID- 8303992
TI  - Nursing and pastoral care working together during the holiday season.

PMID- 8303993
TI  - The advanced practice nurse: searching for a definition.

PMID- 8303994
TI  - Nursing the family: care and knowledge in action. Interview by Patricia Marck.

PMID- 8303996
TI  - Report on "Nursing Ethics in the 90's" conference.

PMID- 8303995
TI  - Travel or contract nursing (USA).

PMID- 8303997
TI  - Choose your response to being let go.

PMID- 8303998
TI  - Financial planning: meat and potatoes style.

PMID- 8303999
TI  - International conference: community health nursing research.

PMID- 8304001
TI  - Healthcare cuts hurt women most.

PMID- 8304000
TI  - Male nursing students in obstetrics.

PMID- 8304002
TI  - Nursing practice issues as revealed by nursing practice consultants telephone
      consultations.

PMID- 8304003
TI  - Politically active--we can make a difference.

PMID- 8304004
TI  - Detection and epidemiological typing of Listeria strains--diagnostic methods for
      Listeria infections (a review).

PMID- 8304005
TI  - Response of the cyanobacterium Anabaena doliolum to endosulfan toxicity.
AB  - Anabaena doliolum Bhar. survived up to 3 mg/litre endosulfan on agar plates.
      Inhibition was visible from the beginning of growth at all tested concentrations;
      the LC50 was 2.15 +/- 0.07 mg/l (p = 0.05). Though the growth and pigment
      inhibition at concentrations < 1.0 mg/l was not significant, these were severe at
      all other tested concentrations (> or = 1.0 mg/l). The pesticide was detoxified
      by A. doliolum at concentrations of 1.5, 2.5, and 3.0 mg/l. The growth rates were
      more than 90% of the control at 2.5 and 3.0 mg/l, while growth acceleration was
      observed at 1.5 mg/l after the third inoculation. The initial cell density was
      also found to be an influential factor in regulating the toxicity of the
      pesticide, the toxicity being inversely related to the cell density.

PMID- 8304006
TI  - Water soluble complex of palmitic acid in media for cultivation of leprosy
      derived psychrophilic mycobacteria from Mycobacterium leprae infected tissues.
AB  - Palmitic acid and palmitates were transformed into water soluble complexes with
      crystalline heptakis-2,6-di-0-methyl-beta-cyclodextrin. This formulation was
      incorporated into liquid and solid chemically well-defined media. The fatty acid
      served as C and energy source, ammonium thioglycolate as the sole source of N
      with the SH group as further source of energy. Minute amount of dimethyl
      sulfoxide added was used for its known effect on cell membrane permeability. The
      media were inoculated with host grown Mycobacterium leprae cells isolated from
      human, armadillo and Nu mice foot pad lepromata. No growth occurred in the liquid
      medium at 22 or 32 degrees C, but cultures and subcultures of acid fast rods were
      grown at 10 degrees C. Bacilli in the cultures were solid, strongly acid fast
      rods, growing in clumps like globi. Growth on the semisolid media was visible as
      smooth round colonies, of white to ivory in colour, slowly expanding flatly at
      the periphery of the colony on the agar surface. Colonies developed within 2-3
      weeks and reached maximum size at 50-80 days depending on the size of inoculum.
      Subcultures grow faster and more abundantly with adaptation to the media. No
      growth was seen without the water soluble complexes of palmitic acid or
      palmitates in the media. The free fatty acid or its salts had an equal growth
      supporting effect. Identical psychrophilic cultures were obtained from 7 out of 9
      armadillo, 12 out of 12 Nu mice and 1 out of 2 human lepromata. None of the
      cultures grow on Loewenstein, Dubos or 7H9 media at 10 degrees C, 20 degrees C or
      32 degrees C, respectively. The tested 4th to 7th subcultures of the strains were
      strongly positive for phenolic glycolipid-1. Heat killed suspensions of up to 7th
      subcultures gave negative late skin reaction in all of 16 LL cases. In 19 I, B
      and T cases the late skin reactions were all similar to that obtained with
      authentic human lepromin.

PMID- 8304007
TI  - Sensitivity of detection of enterotoxigenic Escherichia coli from stool sample by
      DNA probe.
AB  - An attempt has been made to detect the minimum counts of enterotoxigenic
      Escherichia coli (ETEC) in stool sample under simulated clinical condition.
      Thermostable (ST-la) enterotoxin-producing ETEC culture was mixed with stool
      sample and normal saline, centrifuged, then the supernatant was further diluted
      with saline and different volumes were spotted on nitrocellulose paper.
      Hybridization with 32P labelled pDAS-101 DNA and viable count of original culture
      on MacConkey agar plates with ampicillin revealed that minimum 8 cells of ETEC
      (ST) could be detected. The method of labelling used was sequential harnessing of
      the catalytic and synthetic activity of the large Klenow fragment of DNA
      polymerase-I. Linearizing of the DNA was dispensed with as the nicked circular
      DNA was excised with the gel and used for labelling directly.

PMID- 8304008
TI  - Mutagenic effect of cadmium on Trichoderma viride.
AB  - The effect of cadmium ion on growth and differentiation of the filamentous fungus
      Trichoderma viride was studied. Cd++ at a concentration of 10 mM strongly
      retarded growth and caused morphological changes. From cultures treated with
      cadmium, two white mutants and one yellow mutant were isolated. The white mutants
      formed no conidiophores and one of them produced colourless crystals in the
      cultivation medium. The yellow mutant differed from the parental strain mainly by
      the production of differently coloured conidia and by a slower growth rate.

PMID- 8304009
TI  - Isoelectric focusing isozyme profiles and taxonomic distances among Fusarium
      species of the sections Arthrosporiella and Sporotrichiella.
AB  - Isozymes from 18 isolates representing seven species of the Fusarium sections
      Arthrosporiella and Sporotrichiella were compared by isoelectric focusing in
      polyacrylamide gels. Of the six enzyme systems tested esterase and malate
      dehydrogenase showed the largest variation. A numerical analysis of the pI values
      determined for acid phosphatase, esterase, glucose-6-phosphate dehydrogenase,
      malate dehydrogenase, phosphoglucose isomerase and phosphoglucomutase resulted in
      a dendrogam demonstrating the taxonomical relationships of the seven species.
      Fusarium avenaceum and Fusarium pallidoroseum were the two most closely related
      species. The high degree of isoenzyme dissimilarity among Fusarium
      chlamydosporum, Fusarium poae, Fusarium tricinctum, the fungi that produce
      pyriform or citriform microconidia, suggests that they are distinct species and
      their reduction to a variety level is not reasonable. The taxonomical
      distinctness of Fusarium camptoceras, a lesser known and rarely occurring fungus
      was also proven.

PMID- 8304010
TI  - On functional strain in fixed and removable partial dentures. An experimental in
      vivo study.
AB  - Three rosette strain gauges were attached to a fixed bilateral cantilevered
      crossarch maxillary bridge and one linear strain gauge to an attachment-retained
      removable partial denture (RPD), to study the functional deformation pattern in
      this combined reconstruction. The deformation under clinical conditions at
      maximum habitual biting and at maximum unilateral loading was very complex, with
      both elongation and contraction in different parts of the fixed reconstruction.
      Even though this complexity in the functional deformation was found both with and
      without the RPD incorporated, the RPD seemed to provide a more even and favorable
      distribution of the masticatory forces in the fixed reconstruction.

PMID- 8304011
TI  - Psychometrics in temporomandibular disorders. An overview.
AB  - The purpose of this paper is to review the methods and results of psychometric
      testings in temporomandibular disorders (TMD) during the past decade. Assessments
      of psychologic and behavioral factors have been performed for various reasons.
      The results are often ambiguous and comparisons troublesome. No encompassing
      psychologic TMD profile has been identified, but small elevations in anxiety,
      depression, somatization, and stress are often reported; they may be cause or
      effect. Subcategorization of the patients into diagnostic subgroups suggests that
      psychologic differences exist but may be small; myogenic patients may have more
      psychologic difficulties than 'joint' patients. More distinct, robust psychologic
      subsets of patients, unrelated to the structural diagnosis, have been identified
      by means of clustering techniques. Irrespective of clinical signs, a certain
      proportion of the patients are psychologically distressed, whereas others easily
      adapt to the pain and dysfunction. No single variable has been identified that
      can predict outcome or compliance. Several psychometric instruments are
      described.

PMID- 8304012
TI  - Crystal precipitation on dentin by poly(acrylic acid) solutions containing SO4(2
      ) ions.
AB  - The ability of four different 40% poly(acrylic acid) (PAA) solutions, containing
      4 or 6 wt-% of either Na2SO4 or (NH4)2SO4, to cause precipitation of CaSO4 on
      dentin surfaces was investigated. Each treatment consisted of exposing the dentin
      to one of the four solutions for either 1 or 2 min and was followed by a water
      rinse (1 min) and air drying (30 sec). The treated dentin surfaces were then
      evaluated in a scanning electron microscope (SEM), which showed that crystals
      precipitated on the dentin with these solutions. Of the four investigated PAAs,
      one performed better than the others with regard to crystal precipitation and
      blockage of the tubules. This solution was selected for additional studies of the
      effects of different PAA concentrations (10%, 20%, 30%, 40%, and 50%). In these
      solutions, 4 and 6 wt-% of either Na2SO4 or (NH4)2SO4 were dissolved. Additional
      dentin surfaces were then treated with these solutions as described earlier and
      evaluated in an SEM. This evaluation showed that solutions containing 30-50% PAA
      resulted in optimized crystal formation for all the different sulfate solutions
      and that the optimization occurred within 1 min. Besides optimizing crystal
      precipitation, these mixtures also minimized the frequency of open dentinal
      tubules.

PMID- 8304013
TI  - Evaluation of damage to removable dentures in two cities in Finland.
AB  - The number of damaged dentures and type of damage to removable dentures repaired
      in dental laboratories was investigated using a questionnaire sent to 24 dental
      laboratories in Finland. Eight variables were examined for each damaged denture.
      The results showed that the type of dentures most commonly needing repair was the
      complete upper denture (49%). The most frequent type of damage was breakdown of
      the acrylic base and loosening of an artificial tooth. The chi-square test
      established a statistical dependence (p < 0.005) between damaged dentures and
      their age. Damaged upper partial dentures most frequently had natural teeth or
      fixed prostheses as antagonist teeth. Damaged lower skeletal dentures and acrylic
      partial dentures had a complete denture as the antagonist (p < 0.05). Removable
      dentures made of acrylic resin material seemed to break despite strengtheners,
      such as clasp wire.

PMID- 8304014
TI  - An analysis of primary and contributing reasons for extraction of permanent teeth
      given by the dentist.
AB  - The aim of the present study was to collect information about primary, secondary,
      and tertiary reasons that dentists gave for extracting permanent teeth and to
      determine whether and how dentist-associated characteristics might influence the
      relative emphasis on clinical diagnosis versus non-disease considerations given
      as reasons. A national random sample of Norwegian dentists (n = 500) recorded
      reasons for tooth extraction during a period of 2 weeks in 1988 (response rate,
      70%). Nine hundred and eight-five teeth were extracted from 692 patients. Disease
      /condition-related diagnoses topped the list for primary and secondary reasons
      for extraction, whereas patients' wishes, economy, and esthetics came to the
      forefront among tertiary reasons. Logistic regression analysis showed that the
      choice between clinical diagnosis and non-disease considerations as primary and
      secondary reasons for extraction was significantly but moderately influenced by
      variables associated with the dentist.

PMID- 8304015
TI  - Plaque pH and oral retention after consumption of starchy snack products at
      normal and low salivary secretion rate.
AB  - The effect of plain potato chips, sugar-free cheese doodles, and sweetened
      crackers on plaque pH and oral retention was tested in 10 volunteers and compared
      with 5% starch and 5% sucrose, during both normal and low salivary secretion
      rate. The first 30 min 5% sucrose gave the most and 5% starch the least
      attenuated pH drop, but the three snack products reached or even passed the level
      seen by sucrose during the second 30-min phase. All products resulted in greater
      pH falls and remained at a low level for a longer period during low secretion
      rate. There were no differences in concentration of carbohydrates in saliva after
      consumption of potato chips, cheese doodles, and a cracker. However, low
      secretion rate increased the oral retention for all three products. To conclude,
      this study showed that low salivary secretion rate accentuated the pH decrease in
      dental plaque and prolonged the oral retention of carbohydrates.

PMID- 8304016
TI  - Per- and post-operative variables of mandibular third-molar surgery by four
      general practitioners and one oral surgeon.
AB  - Per- and post-operative indicators in 25 patients who had lower third-molar
      surgery performed by 4 general practitioners (GP) in their own practices were
      compared with those of a control group of 25 patients operated on by an oral
      surgeon. The preoperative variables age; sex; general health; use of medications,
      alcohol, and tobacco; and depth, position, and presence of infection of the third
      molar were considered in individual matching of the patients. The operations
      performed by the GPs lasted 17.9 min (p = 0.0001) longer than those of the oral
      surgeon. Increased rates of postoperative alveolitis (p = 0.03) and secondary
      healing (p = 0.0005) were found in the GP patient group, as was a tendency for
      increased postoperative pain and consumption of strong analgesics. The number of
      days unable to work was 1.9 in the GP group, compared with 0.6 in the surgeon
      group (p = 0.0012). No differences in swelling and trismus were found.

PMID- 8304017
TI  - Atrial natriuretic peptide, blood volume, aldosterone, and sodium excretion
      during twin pregnancy.
AB  - BACKGROUND: The reports on plasma concentrations and physiological function of
      atrial natriuretic peptide (ANP) during pregnancy are conflicting. In a recent
      prospective study, including 40 healthy primigravidae, we found a highly
      significant decrease in the plasma concentration of ANP (p-ANP) during the third
      trimester and the results indicated that ANP takes part in regulation of blood
      volume and renal function during pregnancy as in the nonpregnant state. In order
      to test these results, a study was performed in primigravidae with twin pregnancy
      to test if the accentuated physiological changes here were followed by a
      corresponding greater decrease in p-ANP. METHODS: Ten healthy primigravidae with
      twin pregnancy were examined four times during pregnancy plus 12 weeks after
      delivery. Each time the following were measured: p-ANP, aldosterone, renin, blood
      volume (carbon monoxide), cardiac output (Doppler), blood pressure and sodium
      excretion. Interdependence of the changes in ANP and in the other parameters was
      tested using Spearman's rank correlation test on the delta (delta)-values (the
      differences in measurements between investigations). The results were compared to
      the results obtained during singleton pregnancy using the Mann-Whitney rank sum
      test. RESULTS: All pregnant values of p-ANP during twin pregnancy were lower than
      12 weeks after delivery, p < 0.01. In the 20th, 28th, and 32nd week p-ANP was
      lower in twin pregnancy than in singleton pregnancy, p < 0.05. There was a
      negative correlation between changes in p-ANP and changes in: a) blood volume, R
      = -0.8, p < 0.0001, b) aldosterone, R = -0.66, p < 0.0001, c) renin, R = -0.52, p
      < 0.01, d) cardiac output, R = -0.68, p < 0.0001. There was a positive
      correlation between changes in p-ANP and changes in: a) fractional excretion of
      sodium, R = 0.73, p < 0.0001, and b) total peripheral resistance, R = 0.61, p <
      0.0001. CONCLUSION: The results suggest that the competitive relationship between
      ANP and the renin-aldosterone system in regulating sodium balance and fluid
      volume is preserved during pregnancy. The vasodilation during pregnancy is not
      mediated by ANP.

PMID- 8304018
TI  - Endothelin-1,2 levels in umbilical vein serum of intra-uterine growth retarded
      fetuses as detected by cordocentesis.
AB  - INTRODUCTION: The objective of this study was to determine whether the
      circulatory levels of endothelins, potent vasoconstrictor polypeptides produced
      mainly by endothelial cells, are increased in growth-retarded fetuses. STUDY
      DESIGN: Fetal venous serum samples, withdrawn by ultrasound-guided cordocentesis
      from 11 growth-retarded fetuses and 10 normally-growing fetuses who underwent the
      procedure because of other unrelated indications, were examined for
      immunoreactive endothelin-1,2 by radioimmunoassay. RESULTS: Higher mean
      endothelin-1,2 levels were found in the sera of growth-retarded fetuses than in
      controls (16.8 +/- 4.2 versus 10.9 +/- 4.3 fmol/ml, p = 0.008). Within the growth
      retarded group, there were no differences in endothelin-1,2 levels in the
      presence of either abnormal umbilical Doppler, asymmetry of growth-retardation,
      maternal signs of preeclampsia, or fetal acidosis. CONCLUSION: High levels of
      endothelin-1,2 in the fetoplacental circulation may be pathophysiologically
      important in fetal growth retardation. However, the clinical significance of
      these elevated levels is yet to be determined.

PMID- 8304019
TI  - Outcome for fetuses with abdominal wall defects detected by routine second
      trimester ultrasound.
AB  - The outcome for 70 fetuses with abdominal wall defects detected by routine second
      trimester ultrasound during the years 1983-90 was investigated. In 65 of the 70
      cases the prenatal diagnoses were correct. Thirty-two women had their pregnancies
      terminated by legal abortions. Thirty-eight pregnancies continued. Six of these
      ended with spontaneous abortion or intrauterine fetal death. Thirty-two infants
      were born alive. Nearly all cases with associated malformations and all cases
      with chromosomal defects were in the omphalocele group. The neonatal survival for
      infants with gastroschisis and infants with omphalocele without associated
      malformations or chromosomal defects was high (96%).

PMID- 8304020
TI  - Modern treatment of unruptured ectopic pregnancy.

PMID- 8304021
TI  - Objectively measured tobacco exposure among pregnant women in Finland in 1986 and
      1990.
AB  - OBJECTIVE: First, to study tobacco exposure among pregnant Finnish women in 1986
      and 1990. Second, to study the objectively measured exposure in different
      socioeconomic classes and in different geographical regions. Third, to assess the
      value of serum thiocyanate concentrations in estimating fetal tobacco exposure.
      DESIGN: Tobacco exposure was measured from maternal and umbilical serum samples
      by measuring the concentration of nicotine metabolite, cotinine. In addition, the
      concentrations of thiocyanate were measured from umbilical serum samples. The
      occupations of the mothers were obtained from the Finnish Birth Registry, and the
      area of residence from laboratory records. SETTING: Finland. SUBJECTS: 1323
      infants born in late February-early March in 1991, 1263 mothers of these infants
      during antenatal visits in Autumn 1990, and 976 pregnant mothers during antenatal
      visits in Autumn 1986. The mothers and infants studied represented all newborn
      infants and their mothers during one week in one country. MEASUREMENTS AND MAIN
      RESULTS: In 1986, 21.3% of Finnish mothers and in 1990 21.2% were exposed to
      tobacco. In 1986, exposed mothers were on average 1.4 (95% confidence interval
      0.9-1.8) years younger than nonexposed mothers, and in 1990, exposed mothers were
      on average 1.6 years (95% confidence interval 1.1-2.3) younger than nonexposed
      mothers. 28.5% of mothers classified as unskilled workers were exposed, but only
      9.1% of those classified as upper white-collar. There were no significant
      geographical differences in exposure. Although umbilical serum thiocyanate levels
      were always elevated in exposed infants, high serum thiocyanate concentrations
      were detected in infants not exposed to tobacco. CONCLUSIONS: More than 20% of
      pregnant Finnish mothers and their fetuses were exposed to tobacco in 1986 and
      1990. Young women and women in low socioeconomic classes were the most seriously
      exposed. Measurement of serum thiocyanate concentrations did not yield reliable
      estimates of exposure.

PMID- 8304022
TI  - Cervical incompetence and cerclage in Denmark 1980-1990. A register based
      epidemiological survey.
AB  - OBJECTIVE: To assess the incidence rate of cervical incompetence diagnoses in
      Denmark 1980-1990 according to maternal age, to analyse regional variations, to
      investigate how often cerclage is applied, and finally to estimate abortion rates
      among women with cervical incompetence with and without cerclage. DESIGN: A
      register-based retrospective cross section study. SETTING: All Danish
      gynecological departments. MATERIAL AND METHODS: Since 1977, all hospitalized
      patients in Denmark have been centrally recorded by diagnosis according to the
      ICD classification and by operation codes in The National Patient Register. From
      this database, all women with cervical incompetence (CI) and cerclage in the
      period 1980-1990 were identified. From the same database all cases of spontaneous
      abortions were registered. RESULTS: A total of 2756 cases of cervical
      incompetence were registered in the period 1980-1990, corresponding to an
      incidence rate of 4.6/1000 births. The risk of cervical incompetence increased
      from 2/1000 births among women 15-19 years old to 7.5/1000 births among women 35
      39 years old. The incidence rate of the CI-diagnosis fell 44% from 1980 to 1990.
      The incidence rates in different counties ranged from 1.7/1000 births to
      10.0/1000 births. The average length of stay in hospital among patients with
      cervical incompetence was three weeks. Among patients with cervical incompetence,
      61% were treated with cerclage. This per cent increased from 29% among women 15
      19 years old to 68% among women 35-39 years old. 13.5% of women with CI
      experienced spontaneous abortion. This percentage increased from 12% for women 15
      19 years old to 17% among women 40-44 years old (p < 0.01). Among women with CI
      and cerclage, the abortion rate was 17.6%. CONCLUSION: In the period 1980-1990
      the incidence rate of cervical incompetence in Denmark was on the average
      4.6/1000 births. The incidence rate of the CI-diagnoses has fallen significantly
      during the last decade, and it increases four-fold with increasing age. Six out
      of ten patients with cervical incompetence were treated with cerclage.

PMID- 8304023
TI  - Is fetal heart rate variability a good predictor of fetal outcome?
AB  - OBJECTIVE: The purpose of this study was to investigate, in a prospective manner,
      whether fetal heart rate (FHR) variability serves as a reliable single predictor
      of fetal outcome. METHODS: We undertook a prospective study of 2,200 consecutive
      deliveries. Preterms < 37 weeks, twins, stillbirths and fetal malformations were
      excluded from the study. FHR tracings were analyzed for variability in every
      delivery. Three windows were evaluated: 1) early in labor (30 min); 2) in the
      active phase of labor - 1 h prior to complete cervical dilatation (30 min); and
      3) throughout the second stage of delivery, in segments of 30 min. Using the
      tracings taken at admission and prior to delivery, FHR variability was scored
      according to five previously used evaluative methods, and was correlated to the
      following three fetal outcome parameters: a) arterial cord blood pH < 7.2, > 7.2;
      b) 5-min Apgar >6, < 7; and c) immediate outcome ('good' defined as newborn going
      home after 2-5 days, with no neonatal intensive care unit (NICU) admission).
      RESULTS: 1. The majority of cases with adverse fetal outcome exhibited good FHR
      variability (mean, 80%). 2. Low FHR variability is not common in newborns with
      adverse general outcome (mean, 11.5%). 3. The predictability of FHR variability
      (using the five most common scoring methods) for evaluating adverse fetal outcome
      revealed low sensitivity (mean, 20.3%) and low predictive value (mean, 11.6%).
      CONCLUSION: FHR variability by itself cannot serve as the only indicator of fetal
      wellbeing. The presence of low variability should alert the physician; however,
      good FHR variability should not be interpreted as reassuring.

PMID- 8304024
TI  - Persistent occiput posterior presentation--a clinical problem.
AB  - In order to find out how often labor is complicated by persistent occiput
      posterior position, (OPP), and how it affects the course and outcome of labor,
      the records of 3648 deliveries were reviewed, a frequency of 4.7% was found.
      Also, the amount of operative deliveries was surprisingly high, less than half of
      these cases were delivered without operative intervention. Total duration of
      labor, stage II of labor were both significantly longer in the OPP group. The
      children in the OPP group also were significantly heavier (79 g) than the average
      birthweight in the whole material.

PMID- 8304025
TI  - Choice of contraceptive modality by women in Norway.
AB  - STUDY OBJECTIVE: To investigate the use of contraception in a representative
      sample of Norwegian women. OUTCOME MEASURES: Frequency distribution of
      contraceptive methods by age, marital status and partly strata. MATERIAL: A
      sample of 4,933 women were selected at random from the Central Population
      Register as participants in the second Norwegian fertility study (1988). The
      response rate was 81% (n = 4,019) and personal interviews of contraceptive use
      were carried out among 2,782 women who were fecund, sexually active and not
      pregnant. These women comprise the study population. RESULTS: 2,782 women were
      sexually active during the last month prior to the interview and thus in
      potential need of contraception. More than 50% of the women used either oral
      contraceptives (21%) or IUDs (30%). The use of oral contraceptives decreased
      linearly with age from a user rate of 60% among women 20-24 years old to 1.5%
      among women 40-44 years of age. The use of IUDs increased from 6% in the youngest
      age group to nearly 40% among women aged 30-39 years of age. Oral contraceptives
      were preferentially used by childless women or those with only one child, while
      IUDs were most often used by women with two or more children. The sterilisation
      rate increased by age and in the 40-44 age group one out of every three women was
      sterilised. Non-use was most frequent among the subgroups of women who planned
      children in the future. Use of condoms and other coitus-dependent contraceptives
      varied less with age, marital status and parity than did the use of OC, IUDs or
      sterilisation. CONCLUSION: The user pattern concerning different contraceptive
      methods reflects the general guidelines for contraceptives in Norway. The fact
      that nearly 70% of the women were in one of the three categories--OC or IUD
      users, or one of the partners was sterilised--reveals that the awareness and
      knowledge of modern contraception is high in Norwegian society.

PMID- 8304026
TI  - Cerebral palsy trends. Implications for perinatal care.

PMID- 8304027
TI  - Tubal patency studied by ultrasonography. A pilot study.
AB  - Transvaginal hysterosalpingoultrasonography (HSUG) was performed using a uterine
      cannula and Ringer's solution (Kabi Baxter) as a contrast agent in 14 women
      consulting for infertility. The results were compared with those of
      chromopertubation at laparoscopy/laparotomy. With HSUG, the uterine cavity was
      always well visualized, though it was more difficult to evaluate tubal status. As
      compared with those of the other methods, HSUG findings manifested total
      agreement in 50% of cases, total disagreement in 22%, and partial agreement in
      the remaining 28%. The method was well tolerated by the women studied, and six
      out of nine women who had previously undergone hysterosalpingography (HSG) found
      HSUG to cause less discomfort. Thus, the findings suggest that HSUG might prove
      useful as a means of ascertaining tubal status at an early stage in infertility
      evaluations.

PMID- 8304028
TI  - Relief of dysmenorrhea associated with septate uteri after abdominal or
      hysteroscopic metroplasty.
AB  - We analyzed the postoperative modifications of dysmenorrhea in 90 patients with
      septate or subseptate uterus, but no other genital or pelvic disorders, who
      underwent metroplasty according to Tompkins (n = 28) or hysteroscopic metroplasty
      (n = 62). The frequency of dysmenorrhea fell from 50% to 32.1% after the
      Tompkins' procedure and from 54.8% to 17.7% after hysteroscopic metroplasty. The
      severity of dysmenorrhea evaluated with two scales, one linear and one
      multidimensional, showed a significant postoperative decrease in both the groups.
      In view of the limited cost and low risks of hysteroscopic metroplasty, primary
      dysmenorrhea associated with septate or subseptate uterus may be considered an
      indication for this intervention.

PMID- 8304029
TI  - Endometriosis in monozygotic twins.
AB  - OBJECTIVE: To study the reproductive and medical history of monozygotic twin
      sisters and mothers of patients with endometriosis. MATERIAL AND METHODS: Among
      515 patients with endometriosis, eight had a monozygotic twin sister all of whom
      had had a gynecological laparoscopy or laparotomy. In addition, five of their
      mothers had had a laparotomy. Details about these 13 relatives were obtained
      either from medical records (ten cases) or by unmistakable reports from the
      proband (three cases). RESULT: Six of the monozygotic twin sisters (75%) also had
      symptomatic endometriosis compared with 3.8% among other types of sisters (p <
      0.0005). Three of the mothers (38%) had either endometriosis or adenomyosis.
      CONCLUSION: This study gives support to the assumption that endometriosis has a
      genetic trait.

PMID- 8304030
TI  - Screening voided urine for Chlamydia trachomatis in asymptomatic adolescent
      females.
AB  - First catch urine (FCU) from 751 asymptomatic adolescent female high school
      students, with sexual debut, were screened for the presence of Chlamydia
      trachomatis (Group A). The prevalence of C. trachomatis infection in Group A was
      2.1% (16/751). In Group B, 619 asymptomatic adolescent females attending a youth
      and a family planning clinic were screened for C. trachomatis by testing FCU and
      cervical specimens. An enzyme immunoassay (IDEIA-III) was used to detect C.
      trachomatis verified by fluorescein isothiocyanate-conjugated (FITC) monoclonal
      antibodies. Only samples positive in both tests were regarded as true positive.
      The cervical samples from the women in Group B were positive in 7.8% (48/619),
      while the FCU were positive in 6.0% (37/619). Detection of C. trachomatis by EIA
      in FCU samples was found useful for screening females for genital chlamydial
      infection. The prevalence of C. trachomatis in an unselected asymptomatic
      population was found to be lower than in age-matched individuals seeking medical
      advice in the same coherent area.

PMID- 8304031
TI  - The role of ultrasound scan in childhood ovarian tumors.
AB  - Seven cases with childhood ovarian tumors are presented. All underwent an
      ultrasound scan which gave the the preliminary diagnosis of ovarian tumor.
      Treatment differs according to the status of the child and whether malignity is
      involved. The numerous differential diagnoses must be kept in mind. The
      management of children with an unexplained abdominal mass should include an
      ultrasound scan.

PMID- 8304032
TI  - Synergistic effects of carboxymethylcellulose and low molecular weight heparin in
      reducing adhesion formation in the rat uterine horn model.
AB  - OBJECTIVE: To investigate the effect of sodium carboxymethylcellulose (SCMC) and
      the combination of low molecular weight heparin (LMWH) with SCMC in the
      prevention of intraperitoneal adhesion. DESIGN: Thirty-eight rats underwent
      bilateral surgical injury to the uterine horn and the parietal peritoneum. In 13
      rats, a solution of SCMC was instilled at laparotomy. In 11 rats, LMWH was
      delivered on to serosal and peritoneal defects, and SCMC was instilled. As a
      control group 14 rats were included in the study. SETTING: Surgical Research
      Laboratory, Erciyes University. PARTICIPANTS: Female Wistar-Albino rats, weighing
      200 to 250 g each. MAIN OUTCOME MEASURES: Adhesions between the uterine horn and
      the abdominal sidewall were scored for extent and severity two weeks after the
      initial surgery. RESULTS: Although the mean adhesion score both in the SCMC group
      (2.8, s.d. 1.15) and in the SCMC with LMWH group (1.6, s.d 1.18) was found to be
      significantly lower than in the control group (3.4, s.d. 0.89) (p < 0.05 and p <
      0.001, respectively), more favorable adhesion prophylaxis was achieved in the
      SCMC with LMWH group in comparison with the SCMC treatment group without any
      hemorrhagic complications (p < 0.001). CONCLUSION: We conclude that SCMC with
      LMWH are highly effective in reducing postoperative adhesions in this animal
      model. SCMC with LMWH appears promising in adhesion prophylaxis.

PMID- 8304033
TI  - Antithrombin III in fetuses and newborn children.
AB  - Antithrombin III (AT III) was measured in plasma of healthy fetuses between 20-29
      weeks of gestation, in plasma of suspected growth retarded or malformed fetuses
      between 30-39 weeks of gestation, in healthy newborn infants after delivery, and
      in healthy infants during the first year of life. Measurements were performed
      with an AT III assay (Orion Diagnostica, Espoo, Finland Turbox) on nephalometer
      Turbox. The results were expressed as a percentage of the mean adult value (300
      mg/l) and statistically analysed with the non-parametric Kruskal-Walles test. AT
      III levels in fetuses were low but increasing. They continued to increase after
      birth (F = 34.53 p < 0.001) and reached adult values in the age between the tenth
      and twelfth month of life.

PMID- 8304034
TI  - Bilateral virilizing hilus (Leydig) cell tumors of the ovary.
AB  - A 72-year-old postmenopausal woman with high plasma testosterone levels and
      virilization, as demonstrated by hirsutism and balding, is presented. Urinary 17
      ketosteroids and 17-hydroxycorticosteroids, as well as computed axial tomography
      scan of the adrenal glands were normal. Although no pelvic mass was detected by
      ultrasonography or pelvis examination, the patient was found to have small
      bilateral hilus cell tumors of the ovary. Following bilateral salpingo
      oophorectomy the plasma testosterone dropped to normal level. This is the third
      case of bilateral hilus cell tumors of the ovary to be reported.

PMID- 8304035
TI  - Multiple leiomyomata of the urinary bladder in a hysterectomized woman.
AB  - A 47 year-old previously hysterectomized para 0 gravida 0 presented with
      hematuria, abdominal pain and a palpable pelvic mass. Cystoscopy was normal. An
      ovarian tumor was suspected. At operation three leiomyomata originating from the
      bladder wall were found. This is a rare disease with only about 160 cases
      hitherto reported in the literature. The present case represents, as far as I
      know, the first case of multiple bladder leiomyoma reported in a woman. Bladder
      leiomyomata are a very rare differential diagnosis to ovarian tumors.

PMID- 8304036
TI  - Leiomyomatosis peritonealis disseminata.
AB  - Leiomyomatosis peritonealis disseminata is a very rare disorder. The number of
      cases documented in the literature is only 44. Of these cases, only one was in
      the postmenopausal period. We report a new case of leiomyomatosis peritonealis
      disseminata in a postmenopausal woman.

PMID- 8304037
TI  - Outcome of pregnancy and childbirth following laryngectomy.
AB  - OBJECTS: Pregnancy and delivery in two laryngectomized women. RESULTS: One woman
      had a pregnancy complicated by hypothyroidism and stenosis of the tracheostoma,
      she was delivered by cesarean section. The other had an uneventful pregnancy and
      a spontaneous vaginal delivery. CONCLUSIONS: Individualized handling of the
      delivery. By modifying the technique of bearing down spontaneous vaginal delivery
      is possible.

PMID- 8304038
TI  - [Functional surgery of the larynx: the state of the art: a discussion].

PMID- 8304039
TI  - [A comparison between the "bithermal caloric test" and the "hot monothermal with
      simultaneous cold test"].
AB  - Hot (44) and cold (30) caloric test are the most common tool to investigate canal
      activity. Many authors, otherwise, have pointed out that this method is very long
      needing about five minutes of interval among the irrigations and that it is often
      troublesome for the patient that is exposed four times to a vertigo. To
      investigate vestibular function some of these authors tried to use the hot
      monothermal test alone but results were poor. The aim of this study was to
      propose a shorter and a less troublesome method of investigation and to introduce
      a new diagnostic possibility not pointed out with traditional caloric test. We
      have tried to determine some new reliable diagnostic criteria modifying
      confidential value of the hot monothermal test and considering the eventual
      presence of the nystagmus and its direction during the cold simultaneous test; on
      the basis of this results we are able to distinguish a normal vestibular function
      from a labyrinthine preponderance or a directional preponderance or an aspecific
      disfunction. When the vestibular function is normal or when there is a
      labyrinthine preponderance our results are in total accord with those achieved
      with the traditional bithermal test. Therefore we suggest to use always the hot
      monothermal test associated with the cold simultaneous test, performing the two
      cold irrigations in additions, only in the case of a directional preponderance or
      an aspecific disfunction.

PMID- 8304040
TI  - [Empirical Italian chirugeons and the performance of rhinoplasty in the 15th
      century].

PMID- 8304041
TI  - Osteopenia and bone-remodeling abnormalities in warfarin-treated lambs.
AB  - The physiologic role of osteocalcin (OC), a vitamin K-dependent protein specific
      to bone, remains elusive. It has been shown that rats maintained on chronic
      treatment with vitamin K1 and its antagonist warfarin exhibit a marked decrease
      in bone osteocalcin because noncarboxylated osteocalcin does not bind to bone
      hydroxyapatite. To assess the role of OC in bone remodeling, we applied the
      warfarin model to growing lambs. We analyzed the bone changes after 3 months of
      concurrent warfarin and vitamin K1 treatment. Four groups of four lambs were
      constituted at birth and received daily a saline solution (control group, CT), 4
      mg/kd/day of vitamin K1 (vitamin K group), 4 mg/kg/day of vitamin K1 + 75 or 150
      mg/kg/day of warfarin (W75 and W150 group, respectively). In warfarin-treated
      animals, bone osteocalcin levels were decreased, both in the metaphysis (9%
      compared to controls) and the diaphysis (30% compared to controls) of the
      metacarpals. The fraction of noncarboxylated osteocalcin measured every month in
      the serum was significantly higher in warfarin-treated lambs than in controls at
      each timing point (37.6 +/- 2.6% in W75 and 48.7 +/- 5.2% in W150 versus 14.4 +/-
      3.8% in controls at 3 months). Compared to non-warfarin-treated animals (NW), the
      main histomorphometric parameters measured on the iliac crest after tetracycline
      double labeling were significantly reduced in the warfarin-treated lambs: 12.2 +/
      5.2 versus 18.6 +/- 4.7% in NW (p < 0.03) for the cancellous bone area, which
      reflects the trabecular bone density; 14.7 +/- 6.1 versus 21.0 +/- 3.6% in NW (p
      < 0.03) for the eroded perimeter, and 0.315 +/- 0.064 versus 0.561 +/- 0.23
      microns 3/microns 2/day in NW (p < 0.02) for the tetracycline-based bone
      formation rate. In conclusion, the depletion of osteocalcin in the bone of lambs
      induced within 3 months a marked osteopenia that resulted from a decrease in
      resorption and a more pronounced decrease in bone formation. Our data suggest
      that the presence of osteocalcin, the major gla-containing protein of bone, may
      be important for the maintenance of a normal bone mass and remodeling of
      trabecular bone.

PMID- 8304042
TI  - A 5-year longitudinal study of forearm bone mass in 307 postmenopausal women.
AB  - We measured forearm bone mineral content at the beginning and end of a 5 year
      period in 307 untreated postmenopausal volunteers. We also measured height,
      weight, and a number of biochemical variables in plasma and urine after an
      overnight fast. The initial mean age of the subjects was 59.0 years (range 39
      72), and the mean years since menopause was 10.0 (range 1-37). The mean forearm
      BMC fell from 1034 +/- 9.6 (SEM) to 982 +/- 9.3 mg/cm (P < 0.001). The
      coefficient of correlation between the first and second measurements was 0.96.
      The mean rate of change was -1.0% per annum (with a 99% range of -4 to 1% per
      annum), which agreed well with previous estimates from cross-sectional data.
      There was a significant negative correlation between rate of change in bone mass
      and initial value (r = -0.23; P < 0.001), which was eliminated by expressing
      change as a percentage of initial bone mass. Of the other variables measured, the
      one that was most significantly related to the percentage change in bone mass was
      the urinary hydroxyproline/creatinine ratio (r = -0.35; P < 0.001), which we
      regard as a marker only. By stepwise regression, the only significant
      determinants of the rate of change in bone mass were body weight (positive, P <
      0.001), years since menopause (positive, P < 0.005), urine calcium (negative, P <
      0.01), and serum estrone (positive, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304043
TI  - Changes in markers of bone formation and resorption in a bed rest model of
      weightlessness.
AB  - To study the mechanism of bone loss in physical unloading, we examined indices of
      bone formation and bone resorption in the serum and urine of eight healthy men
      during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of
      resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline
      (Hyp)/g creatinine--during the first few days of inactivity were paralleled by
      tartrate-resistant acid phosphatase (TRAP) with significant increases in all
      these markers by day 4 of bed rest. An index of formation, skeletal alkaline
      phosphatase (SALP), did not change during bed rest and showed a moderate 15%
      increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC)
      began increasing the day preceding the increase in Hyp, remained elevated for the
      duration of the bed rest, and returned to pre-bed rest values within 5 days of
      reambulation. Similarly, DPD increased significantly at the onset of bed rest,
      remained elevated for the duration of bed rest, and returned to pre-bed rest
      levels upon reambulation. On the other hand, the other three indices of
      resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation.
      The most sensitive indices of the levels of physical activity proved to be the
      noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest
      values of both these markers were significantly elevated compared to both the pre
      bed rest values and the post-bed rest values. The sequence of changes in the
      circulating markers of bone metabolism indicated that increases in serum OC are
      the earliest responses of bone to head-down tilt bed rest.

PMID- 8304044
TI  - Relationship between quadriceps strength and bone mineral density of the proximal
      tibia and distal forearm in women.
AB  - It is well known that there is a relationship between muscle strength and bone
      density, but it is uncertain whether this relationship is site specific. The aim
      of this study was to assess the relationship of quadriceps strength to site
      specific bone mineral density (BMD) of the tibia and to BMD of the forearm. In 66
      healthy women, aged 21-78 years, BMD was measured in the proximal tibia and the
      distal forearm by dual-photon absorptiometry. Isometric and isokinetic strength
      of the quadriceps was measured using an isokinetic dynamometer (Cybex II). Highly
      significant correlations between BMD of the proximal tibia and quadriceps
      strength were found (RS ranging from 0.79 to 0.84, p < 0.0001). Also, BMD of the
      distal forearm was correlated with quadriceps strength (RS ranging from 0.59 to
      0.62, p < 0.0001). In a stepwise multiple regression analysis, quadriceps
      strength was a better predictor of tibial BMD than age, body height, or weight.
      However, age, height, and weight were more predictive of forearm BMD than
      quadriceps strength. When studying the pre- and postmenopausal women separately,
      quadriceps strength was correlated with BMD of the proximal tibia but not to
      forearm BMD. In conclusion, the study provides support for a site-specific
      relationship between muscle and bone.

PMID- 8304045
TI  - Effects of high calcium concentration on the functions and interactions of
      osteoblastic cells and monocytes and on the formation of osteoclast-like cells.
AB  - The present study was performed to clarify the role of high calcium concentration
      and the appearance of mononuclear cells at the resorptive site in bone
      remodeling. Our recent study revealed that the high concentration of
      extracellular calcium ([Ca2+]e) stimulated DNA synthesis in osteoblastic MC3T3-E1
      cells not only directly but also indirectly via monocytes. Human monocyte
      conditioned medium (CM) significantly stimulated DNA synthesis and inhibited
      alkaline phosphatase (ALP) activity. In contrast, when monocytes were cultured at
      high [Ca2+]e concentrations (more than 3 mM), CM from these monocytes
      significantly stimulated ALP activity in MC3T3-E1 cells. Such stimulatory effect
      of CM was not observed at a high magnesium concentration (Mg2+, 5 mM). Treatment
      of monocytes with the calcium ionophore A23187 did not affect the CM-induced
      effect on DNA synthesis and ALP activity in these cells. To determine the
      migration potency of MC3T3-E1 cells and monocytes toward the high [Ca2+]e,
      chemotaxis assay was performed. The increasing [Ca2+]e (more than 3 mM) induced a
      chemotactic response of MC3T3-E1 cells as well as monocytes, but the high
      concentration of Mg2+ (5 mM) did not induce it. On the other hand, treatment with
      high [Ca2+]e (more than 3 mM) or CM significantly inhibited the 1,25-(OH)2D3
      induced formation of tartrate-resistant acid phosphatase (TRAP)-positive
      multinucleated cells (MNC) from their precursors derived from mouse spleen
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304046
TI  - 1,25-dihydroxyvitamin D3 potentiates fluoride-stimulated collagen type I
      production in cultures of human bone marrow stromal osteoblast-like cells.
AB  - In this study we tested the effects of sodium fluoride (NaF) in serum-free
      cultures of human marrow stromal osteoblast-like [hMS(OB)] cells. NaF (10(-5) M)
      stimulated hMS(OB) cell proliferation up to 220% of control cultures. NaF alone
      did not increase type I collagen production, but in the presence of 1,25
      dihydroxyvitamin D3 [1,25-(OH)2D3] (10(-9) M), NaF enhanced type I collagen
      production in a dose-dependent way to 300% of 1,25-(OH)2D3-treated control
      cultures. The production of alkaline phosphatase (ALP) and osteocalcin (bone gla
      protein, BGP) was also enhanced in the presence of 1,25-(OH)2D3 to 170 and 200%,
      respectively, of 1,25-(OH)2D3-treated controls. Our results suggest that 1,25
      (OH)2D3 potentiates fluoride-mediated anabolism in hMS(OB) cell cultures and
      suggest that osteoblast precursors in bone marrow are targets for fluoride
      action.

PMID- 8304047
TI  - Intranasal calcitonin suppresses increased bone resorption during short-term
      immobilization: a double-blind study of the effects of intranasal calcitonin on
      biochemical parameters of bone turnover.
AB  - Immobilization is associated with increased bone resorption and decreased bone
      formation. We evaluated in a double-blind trial the effect of intranasal
      administration of salmon calcitonin on biochemical parameters of bone turnover in
      32 patients immobilized for a prolapsed intervertebral disk. Calcitonin in a dose
      of two times 200 IU/day partially inhibited the increase in the fasting 2 h
      urinary hydroxyproline/creatinine ratio (OHPr/Cr) and calcium/creatinine ratio
      (Ca/Cr). The increase in OHPr/Cr was 40% less in the calcitonin group compared to
      the placebo group (P = 0.01), and the increase in Ca/Cr was 80% less in the
      calcitonin group (P = 0.04). Calcitonin also partially inhibited the increase in
      serum cross-linked carboxyl-terminal telopeptide of collagen type I (P < 0.05).
      The decrease in serum 1,25-dihydroxyvitamin D after 10 days of immobilization was
      significantly less in the calcitonin-treated group than in the placebo group (14
      versus 29%, respectively; P < 0.05). Intranasal calcitonin did not influence the
      pain scores as measured with a visual analog scale (VAS). The tolerability of the
      nasal calcitonin preparation was excellent. We conclude that nasal salmon
      calcitonin counteracts the early increase in bone resorption induced by
      immobilization.

PMID- 8304048
TI  - Determinants of remission of Paget's disease of bone.
AB  - Bisphosphonates are a safe and effective treatment for Paget's disease of bone,
      but little information is available about the factors influencing the duration of
      remission so obtained. We assessed 60 patients with Paget's disease treated with
      disodium pamidronate (APD). The mean duration of remission was 9.5 months (range
      3-25). The major influences were the initial pretreatment alkaline phosphatase
      (ALP; r = -4.6, p < 0.0001), minimum posttreatment ALP (r = -0.51, p < 0.0001),
      and the rate of response of bone turnover to the first dose of APD (r = 0.61, p <
      0.0001). Multiple linear regression showed that the initial response to treatment
      was the most significant influence. Also, despite a minimum ALP within the normal
      range, the duration of remission varied considerably (4-25 months). This may be
      due to the difficulties in applying a population-based normal range to
      individuals.

PMID- 8304049
TI  - Thyroid hormones increase insulin-like growth factor I content in the medium of
      rat bone tissue.
AB  - The mechanism of action of thyroid hormones on bone is still not clear. At low
      concentrations, they stimulate bone formation; at high concentrations, they
      elicit bone resorption in vitro and in vivo. In the present study we investigated
      the effect of T3 and T4 as well as their active and inactive analogs (TRIAC, SKF
      L-94901, rT3, and DIT) on the IGF-I and TNF-alpha content in the medium of UMR
      106 rat osteoblastic cells and fetal rat limb bones. In the dose-response
      studies, a biphasic increase in medium IGF-I was observed in both cells and limb
      bones, with peak stimulatory concentrations of 10(-8) M for T3 and 10(-7) M for
      T4 in both systems. At higher concentrations, at which thyroid hormones elicit
      bone resorption, the stimulatory effect diminished and finally was no longer
      detectable. The active analogs TRIAC and SKF L-94901 also enhanced IGF-I release
      in UMR-106 cells. The inactive compounds rT3 and DIT failed to increase IGF-I in
      these cultures. The protein content of the cell culture wells exposed to high
      concentrations of thyroid hormones was similar to those containing low
      concentrations, indicating that the decrease in IGF-I content at high doses was
      not due to toxic effects. This was also confirmed by trypan blue exclusion. Time
      course studies with UMR-106 cells revealed a significant increase in medium IGF-I
      after 2 days of incubation. No significant further increase was observed after
      this up to 5 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304050
TI  - Effect of 1,25,28-trihydroxyvitamin D2 and 1,24,25-trihydroxyvitamin D3 on
      intestinal calbindin-D9K mRNA and protein: is there a correlation with intestinal
      calcium transport?
AB  - Although analogs and metabolites of vitamin D have been tested for their
      calciotropic activity, very little information has been available concerning the
      effects of these compounds on gene expression. In this study one analog of
      vitamin D, 1,25,28-trihydroxyvitamin D2 [1,25,28-(OH)3D2], and one metabolite,
      1,24,25-trihydroxyvitamin D3 [1,24,25-(OH)3D3], were tested for their effect on
      intestinal calbindin-D9K mRNA and protein as well as for their effect on
      intestinal calcium absorption and bone calcium mobilization. These compounds were
      also evaluated for their ability to compete for rat intestinal 1,25-(OH)2D3
      receptor sites and to induce differentiation of human leukemia (HL-60) cells as
      indicated by reduction of nitro blue tetrazolium. In vivo studies involved
      intrajugular injection of 12.5 ng 1,25-(OH)2D3 or test compound to vitamin D
      deficient rats and sacrifice after 18 h. 1,25,28-Trihydroxyvitamin D2 had no
      effect on intestinal calcium absorption, bone calcium mobilization, or intestinal
      calbindin-D9K protein and mRNA. Competitive binding to 1,25-(OH)2D3 receptors was
      0.8% of that observed using 1,25-(OH)2D3. However, 20- and 40-fold higher doses
      of 1,25,28-(OH)3D2 (250 and 500 ng) resulted in significant inductions in
      calbindin-D9K protein and mRNA (3.5 to 7.4-fold), although doses as high as 800
      ng were found to have no effect on intestinal calcium absorption or bone calcium
      mobilization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304051
TI  - Effects of the bisphosphonate tiludronate on bone resorption, calcium balance,
      and bone mineral density.
AB  - Bone resorption inhibitors, such as bisphosphonates, are potentially useful in
      treatments aimed at increasing bone mass. Among bisphosphonates, tiludronate has
      proven efficacious in preventing bone loss in postmenopausal women. However, it
      is not clearly established whether bisphosphonates are more potent when given
      intermittently or continuously. We investigated the effects of tiludronate on (1)
      retinoid-stimulated bone resorption in thyroparathyroidectomized rats, (2)
      calcium balance in intact rats, and (3) bone mineral density (BMD) as measured by
      dual-energy x-ray absorptiometry at the levels of the lumbar spine, tail, and
      tibia in 6-month-old rats made osteoporotic by ovariectomy (OVX), in which an
      intermittent cyclic schedule of treatment was compared to continuous
      administration. Tiludronate induced a dose-dependent decrease in retinoid
      stimulated bone resorption. It increased the intestinal absorption and body
      retention of calcium. In OVX rats it caused a time- and dose-dependent increase
      in BMD at the level of the three investigated sites, the effects being maintained
      for at least 8 weeks after the end of therapy. Continuous and intermittent cyclic
      regimens appeared to induce similar increases in BMD. These results indicate that
      tiludronate is efficacious in decreasing bone resorption and increasing calcium
      balance and bone mineral density in rats.

PMID- 8304052
TI  - Evidence that a non-RGD domain in rat osteopontin is involved in cell attachment.
AB  - The bone sialoprotein osteopontin (OPN) promotes cell attachment and spreading
      through its RGD (Arg-Gly-Asp) sequence. To study additional regions of OPN
      involved in cell attachment, peptides of rat OPN were evaluated for their
      capacity to mediate cell binding to wells in vitro. Human gingival fibroblasts
      were incubated on microtiter plates coated with either OPN or OPN peptides. A
      peptide of M(r) 28 kD, obtained after digestion with endoproteinase Arg-C and
      isolated by reversed-phase HPLC, enhanced cell attachment to a similar degree as
      OPN. Sequence analysis showed that the amino terminus of the 28 kD peptide starts
      at Ser142 and therefore does not contain the RGD cell attachment sequence
      (residues 128-130). Cell attachment mediated through both OPN and the 28 kD
      peptide was blocked by the addition of GRGDSPA peptides or LM-609, a monoclonal
      antibody to the integrin alpha V beta 3, a receptor for vitronectin. A variant
      peptide, GRG-ESPA, did not alter cell attachment. Based on these observations, we
      conclude that (1) binding of OPN and the 28 kD peptide to fibroblasts involves
      binding to alpha V beta 3, (2) a site other than the RGD sequence on OPN is also
      involved in binding to integrins, and (3) the binding of this second site to
      alpha V beta 3 is inhibited by RGD-containing peptides.

PMID- 8304053
TI  - Macrophage colony-stimulating factor release and receptor expression in bone
      cells.
AB  - Colony-stimulating factors (CSF) may play a role in bone resorption. To examine
      whether osteoblasts secrete colony-stimulating activity (CSA) in response to
      parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP),
      conditioned medium (CM) from ROS 17/2.8 cells and primary rat osteoblasts were
      examined for induction of clonal growth of cultured rat bone marrow cells.
      Untreated cells constitutively secreted CSA, which increased with PTH and PTHrP
      treatment. The colonies formed were principally comprised of macrophages, and
      preincubation of CM with antiserum to murine macrophage colony-stimulating factor
      (M-CSF) neutralized most of the CSA, suggesting that the osteoblast-derived CSA
      was predominantly due to M-CSF. PTHrP treatment upregulated steady-state M-CSF
      mRNA levels. To investigate a paracrine role for M-CSF in bone we examined bone
      tissue and cells for the M-CSF receptor c-fms using immunohistochemical
      techniques and demonstrated staining of mature osteoclasts both in situ and after
      isolation. We conclude that M-CSF is responsible for the majority of the CSA
      released by PTH- and PTHrP-treated rat osteoblasts. In addition we identified CSF
      1 receptor expression in mature osteoclasts. These data suggest that M-CSF is a
      mediator of osteoblast-osteoclast interaction in PTH- and PTHrP-induced bone
      resorption.

PMID- 8304054
TI  - Parathyroid hormone-related peptide may increase mammary blood flow.
AB  - Amino-terminal fragments of PTHrP were previously shown to increase regional
      blood flow in laboratory animals. Since PTHrP is produced in the lactating
      mammary gland and associated nutrient vessels, we examined the effects of peptide
      fragments of PTHrP on the hemodynamics of the mammary gland of dried sheep. The
      left arterial mammary blood flow measured using ultrasonic flow probes in four
      dried Lacaune ewes was 233 +/- 11 ml/minute. It was significantly increased when
      synthetic human PTHrP-(1-34) or (1-86) fragments were injected into the mammary
      artery. The effect was dose dependent for PTHrP-(1-34), varying between 0.0075
      and 0.3 nmol/kg body weight. PTHrP-(140-173) fragment lacked any vasorelaxant
      activity. Synthetic human endothelin (ET1) decreased arterial blood flow in a
      dose-dependent manner. This decrease was inhibited by PTHrP-(1-34), and this
      inhibition was PTHrP dose related. When ET1 (10 pmol/kg body weight) was injected
      together with PTHrP-(1-86) (100 pmol/kg body weight), only a significant increase
      in mammary blood flow was observed. Thus, PTHrP produced by the lactating mammary
      gland may be involved in the regulation of mammary blood flow.

PMID- 8304055
TI  - Spondylectomy, microsurgical decompression and osteosynthesis in the treatment of
      complex disorders of the cervical spine.
AB  - In 44 patients with complex degenerative, traumatic, neoplastic and infectious
      disorders of the cervical spine an aggressive surgical approach was used,
      consisting of spondylectomy, radical microsurgical decompression and
      osteosynthesis. The patient group consisted of 23 patients with multisegmental
      cervical spondylosis, 9 patients with primary or metastatic malignant tumour
      disease spread along the cervical spine, 6 patients with complex cervical trauma
      and 6 patients with infection affecting one or more cervical segments.
      Considering the heterogeneity of the group of patients treated, a multitude of
      neurological symptoms and signs were present. Excruciating pain was the
      predominant symptom in 84% of the patients, followed by sensory and motor signs
      of varying degrees in 77% and 65% respectively. Involvement of the long tracts
      was present in 51%, gait disturbance in 49% and bladder disfunction in 28%.
      Considering the nature of the underlying disease, in the group with
      multisegmental cervical spondylosis (MSCS), advanced cervical myelopathy was the
      predominant clinical symptom, whereas in those patients with trauma, tumour or
      infection, pain was the leading symptom, followed by disturbed motor and/or
      sensory function. Altogether 59 vertebrae have been removed in the 44 patients.
      In 28 patients spondylectomy was performed at one level, in 15 patients at two
      levels and in one female tumour patient at three levels. In 34 patients an iliac
      crest bone graft was used and in 10 patients bone cement. Within the observation
      period, solid fusion was achieved in all patients. In one tumour patient screw
      loosening was demonstrable at follow-up, but the fusion remained stable. 2
      patients with infectious disease required re-operation due to significant
      loosening of screws and plates. However, after re-stabilization solid fusion was
      achieved. Considering amelioration of specific pre-operative symptoms and signs,
      excruciating pain responded best to the stabilizing procedure, with improvement
      in over 90% of the patients, followed by improvement of sensory and motor
      deficits in 85% and 82% respectively. Improvement in pre-operative gait
      disturbance could be achieved in 81% of the patients, while disturbance of
      bladder function is less likely to improve after surgery with a positive response
      in only 58%. None of the patients became neurologically worse after surgery. With
      regard to the underlying disease, patients with MSCS and tumour had the best
      results with overall improvement in 62% and 75% respectively. While in patients
      with infection improvement could be achieved in 58%, improvement in trauma
      patients was demonstrable in only 34% while in 66% the pre-operative clinical
      status remained unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8304056
TI  - The effect of indomethacin upon cerebral blood flow in healthy volunteers. The
      influence of moderate hypoxia and hypercapnia.
AB  - In a randomized study of healthy volunteers indomethacin bolus injection followed
      by continuous infusion decreased CBF from normal levels ranging from 45 to 80
      ml/100 g/min to levels ranging from 24 to 57 ml/100 g/min. These low levels were
      sustained during a six hour infusion period. Periods of hypoxia during inhalation
      of 17% oxygen and hypercapnia during inhalation of 2-4% CO2 normalized CBF.

PMID- 8304058
TI  - The effect of acetylcholinesterase inhibitor (SDZ ENA 713) for r-CBF and focal
      cerebral ischaemia.
AB  - The purpose of the present study was to examine the effect of
      Acetylcholinesterase inhibitor (AChEI) on r-CBF (group A) and its protecting
      effect on focal ischaemic cell damage (group B). The pial arterial diameter and
      the r-CBF were measured with a width analyzer and with a laser Doppler flowmeter
      through a cat cranial window on the ectosylvian gyrus. The ischaemic area was
      measured histologically. We used intravenous injection of AChEI([-])(S)-N-ethyl-3
      [(1-dimethyl- amino)ethyl]-N-methyl-phenylcarbamate, SDZENA 713, Sands Pharmacy)
      to block AChE. Twenty minutes after injection AChEI (0.6 mg/kg) the pial
      arteriole dilated 108.5 +/- 1.8% and the r-CBF increased 115.4 +/- 2.6%. The pial
      arteriole dilated maximally to 137.6 +/- 6.5% at 120 minutes after injection and
      the r-CBF increased maximally to 137.1 +/- 19.5% at 60 minutes after injection.
      The protecting effect was evaluated using cats and 1 hour of occlusion of the
      middle cerebral artery (MCA). Twenty minutes after injection of AChEI, the pial
      arteriole dilated to 116.7 +/- 2.4% and the r-CBF increased to 111.9 +/- 2.6%
      significantly. During MCA occlusion the r-CBF decreased to 24.7-41.4% in group B
      and 25.1-32.6% in sham group (group C). The pial arteriole dilated 145.0-184.0%
      in group C and 150.7-171.6% in group B during MCA occlusion and 30 minutes after
      reperfusion the pial arteriole returned to 120.0 +/- 3.3% in group C and 123.4 +/
      11.3% in group B. There were no significant changes in the r-CBF and the vessel
      diameter between group B and C during the 2 hours after reperfusion.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8304057
TI  - Experimental study of venous circulatory disturbance by dural sinus occlusion.
AB  - Using a newly devised model of dural sinus occlusion, we investigated the
      pathophysiology of venous haemorrhage as well as venous circulatory disturbance.
      The superior sagittal sinus (SSS) and diploic veins (DV) were occluded in 16
      cats. Intracranial pressure (ICP), cerebral blood volume (CBV) and regional
      cerebral blood flow (rCBF) were measured for 12 hours after the occlusion. At the
      end of the experiment, cerebral water content was estimated. In another 8 cats
      additional occlusions of cortical veins were carried out. In both groups, the
      blood-brain barrier permeability was evaluated with Evans blue or horseradish
      peroxidase. The SSS and DV occlusion produced a significant increase in ICP and
      CBV concomitant with a significant decrease in rCBF. Cerebral water content also
      increased significantly. However, there was no transition of Evans blue and
      horseradish peroxidase through the cerebral vessels, and no haemorrhages could be
      observed. In contrast, the additional occlusion of cortical veins produced
      haemorrhagic infarctions with Evans blue extravasation in 6 out of the 8 cats.
      These data suggest that dural sinus occlusion may lead to an increase in CBV and
      cerebral water content resulting in intracranial hypertension and decreased rCBF.
      The brain oedema in this model seemed to be mainly hydrostatic oedema, and might
      also be contributed by cytotoxic oedema. The additional occlusion of cortical
      veins might be essential in the development of haemorrhage in this model, and the
      blood-brain barrier was also disrupted in these areas.

PMID- 8304059
TI  - Computer assisted quantification of vasospasm on angiograms.
AB  - We describe a new computer-based, automated method for the assessment of in vivo
      cerebral vasospasm. Arterial diameter measurements were performed on post
      processed digital substraction angiographic images, using "pixel" as the unit.
      Vasospasm which was difficult to detect by visual inspection could be measured by
      the "stenosis quantification" program. A computer-assisted method such as we
      describe might decrease the risk of subjective errors.

PMID- 8304060
TI  - Evidence for the participation of vascular endothelium originated humoral factors
      to cerebral vasospasm.
AB  - Vascular endothelium synthesizes mediators which either cause vasorelaxation or
      vasoconstriction. The purpose of this study is to investigate the role of these
      mediators in the pathogenesis of cerebral vasospasm. An inhibitor of endothelium
      derived relaxing factor is haemoglobin; endothelium removal by triton X-100 and
      endothelin-1 caused narrowing in the diameter of basilar artery of the rabbit.
      The pathological, ultrastructural investigations and computerized tomography
      images are in accordance with this finding. These results indicate that not only
      an increase in vasoconstrictor mediator level but also the lack of endothelium
      derived relaxing mediators are responsible of the spasm of the basilar artery.

PMID- 8304061
TI  - Biomechanics of the pons-cord tract and its enveloping structures: an overview.

PMID- 8304063
TI  - The role of humanities and arts in medical education with special reference to
      neurosurgery. Introduction: humanities, art, and the neurosurgeon.

PMID- 8304062
TI  - Vertebral arteriovenous fistula caused by angiography catheter: case report.
AB  - A case of vertebral arteriovenous fistula (VAF) caused by an angiographic
      catheter during coronary angiography in a 30-year-old female is presented. The
      patient complained about a roaring noise in her left ear. Preoperative and
      postoperative angiographic verification of the lesion is presented. The patient
      was treated by a direct surgical trapping of the vertebral artery (VA) proximal
      and distal to the fistula.

PMID- 8304064
TI  - The role of humanities and arts in medical education with special reference to
      neurosurgery. The Hopkins experiment.

PMID- 8304065
TI  - The role of humanities and arts in medical education with special reference to
      neurosurgery. Poetry and the neurosurgeon.

PMID- 8304066
TI  - The role of humanities and arts in medical education with special reference to
      neurosurgery. The importance of visual arts in the life of a neurosurgeon.

PMID- 8304067
TI  - The role of humanities and arts in medical education with special reference to
      neurosurgery. The contributions of neurosurgeons to medical history.

PMID- 8304068
TI  - The role of humanities and arts in medical education with special reference to
      neurosurgery. Parallels between three-dimensional thinking in neurosurgery and
      the development of perspective in art.

PMID- 8304069
TI  - The role of humanities and arts in medical education with special reference to
      neurosurgery. Human face of neurosurgery: possibilities and problems.
AB  - The avenues of development, successes and failures of modern neurosurgery taking
      into account the factors of its humanisation and dehumanisation are analysed. A
      new model of humanisation of neurosurgery to give it a human face for the future
      is outlined. Suggestions are made to prepare the neurosurgeons for 21st century.
      The main pre-condition for the humanisation of neurosurgery in the 21st century
      are that neurosurgeon must not only be Homo Sapiens, but also Homo Moralis.

PMID- 8304070
TI  - The eye, the brain and the camera.

PMID- 8304071
TI  - Cranio-facial approaches for tumours involving the anterior half of the skull
      base.
AB  - Teamwork between neurosurgeons and head and neck surgeons has increased the
      possibility of managing tumours involving the skull base. The authors distinguish
      the anterior half of the skull base into a median and two lateral portions and
      describe the surgical approaches utilized to expose it. The authors present their
      clinical experience in 27 patients with extensive lesions of the anterior half of
      the skull base and their results.

PMID- 8304072
TI  - Multiple intracranial aneurysms: surgical treatment and outcome.
AB  - We report a series of 41 patients with multiple intracranial aneurysms, analyzing
      them by type of surgical treatment and prognosis. We compare our findings with
      those of the largest published series and draw conclusions regarding the most
      appropriate treatment. The upshot would seem to be that morbidity and mortality
      depend chiefly on whether the aneurysms are bilateral or unilateral and on the
      patient's pre-operative status.

PMID- 8304073
TI  - Unruptured aneurysms associated with ischaemic cerebrovascular diseases. Surgical
      indication.
AB  - Out of 3435 patients with ischaemic cerebrovascular disease 2540 cases were
      investigated using cerebral angiography. In 127 of them (5%) aneurysms were
      found, but without clinical evidence of subarachnoid haemorrhage (SAH). 45 cases
      were operated upon and 82 were treated conservatively. Five of these 82 cases
      (6%) suffered from SAH 3 months to 10 years (mean interval 5.6 years) after the
      angiographic diagnosis. Four of these 5 patients with SAH died. Among the 45
      surgical cases follow-up was uneventful in 29 (64%). The other 16 cases
      postoperatively showed neurological deterioration (36%), which was transient in 6
      but with only minor improvement in 10. Of these 10 cases 2 died from cerebral
      infarction related to intra-operative temporary vascular occlusion respectively
      myocardial infarction. Thus surgical mortality was 4% and permanent morbidity
      18%. Causes of postoperative neurological deterioration were partly related to
      general arteriosclerotic changes and special fragility of the ischaemic brain,
      and partly to operative technique (excessive brain retraction, damage to cortical
      veins, occlusion of major vessels or damage to perforators, temporary artery
      occlusion). Apparently in cases with ischaemic cerebrovascular diseases operative
      procedures, which in other cases as a rule are well tolerated, may produce
      harmful effects. Therefore, in these cases, the indication for operative
      treatment of so far silent aneurysms should be restricted to patients who are in
      good general condition with longer life expectancy as far as the vascular disease
      is concerned, and without major neurological deficit. Furthermore, the operative
      technique should be especially gentle and atraumatic.

PMID- 8304074
TI  - How often is a perimesencephalic subarachnoid haemorrhage CT pattern caused by
      ruptured aneurysms?
AB  - BACKGROUND: Angiography is usually recommended in perimesencephalic subarachnoid
      haemorrhage (PM SAH) to rule out a basilar artery aneurysm. However it is not
      known how often aneurysms are found among patients with a CT pattern of PM
      haemorrhage or the frequency of this CT pattern after rupture of posterior
      circulation aneurysms. METHOD: CTs of all SAH caused by posterior circulation
      aneurysms admitted from 1/85 to 12/92 where reviewed by two examiners. Late (>
      72h) examinations were excluded. The remaining CTs were classified in
      perimesencephalic (PM) or non PM. RESULTS: 81 posterior circulation aneurysms
      were collected. Only one PM-like CT pattern was found, due to ruptured posterior
      communicating artery aneurysm (1.3%; 95% Cl (confidence intervals) = .03-6.7%).
      During the same period 37 PM SAH with negative angiographic results were
      admitted. The likelihood of finding an aneurysm in a patient with an early CT
      showing a PM distribution of haematic densities was 2.7% (95% Cl = .07-.14%).
      CONCLUSIONS: Although the probability of finding an aneurysm in a SAH patient
      with a PM CT pattern is low, a complete 4-vessel angiogram must be obtained.

PMID- 8304075
TI  - Surgical treatment of "hindbrain related" syringomyelia: new data for
      pathogenesis.
AB  - 52 patients with "hindbrain related" syringomyelia underwent surgical treatment.
      All patients underwent primary reconstructive surgery at the craniovertebral
      junction. Terminal ventriculostomy was performed as the secondary operation in 2
      cases. The surgical treatment arrested progression of signs in 33 (63.5%),
      stabilized disease in 9 (17%) cases. Postoperative deterioration occurred in 8
      (15%) cases. Mortality was 4% (2 patients). Percutaneous or intra-operative
      injection of myodil and gas into the syrinx, as well as CT, revealed the
      existence of communication with the 4th ventricle in 14 patients. Investigation
      of cerebrospinal and syrinx fluid revealed increased level of IgG, IgM or IgA in
      the syrinx fluid in 16 out of 22 patients. Immunohistological examination of pia
      mater revealed specific staining for IgG. Thus, syrinx formation may be due to
      synergic action of hydrodynamic and immunopathological mechanisms. Results
      indicate that early surgical treatment is preferable to patients with hindbrain
      anomalies and hydromyelia. We consider primary reconstructive operation at the
      posterior fossa as the preferred surgical management of "hindbrain related"
      syringomyelia.

PMID- 8304076
TI  - Reversibility of severe brain stem dysfunction in children.
AB  - The very popular concept of brain death can lead to a defeatist attitude when
      confronted by a patient with severe brain stem dysfunction. This problem is
      compounded by the constant controversy surrounding the establishing of criteria
      to determine brain death. Many young doctors tend to accept the precondition of
      irreversibility as being any condition that is not explicitly listed in the
      examples of potentially reversible conditions. In children, however, with
      compressive brain stem dysfunction, decompressive surgery can lead to a reversal
      of the dysfunction. In the last three years, we have had the opportunity to
      observe 5 children who were deeply comatose and apnoeic. All were suffering from
      compression of the brain stem and experienced dramatic return of brain stem
      function following emergency decompression. The implications of these findings on
      the therapeutic attitude towards compressive brain stem lesions in children are
      exposed. In children with severe brain stem dysfunction, and no evidence of brain
      stem destruction, decompressive surgery should be undertaken before a diagnosis
      of brain death is considered.

PMID- 8304077
TI  - Abnormal response from the sternocleidomastoid muscle in patients with spasmodic
      torticollis: observations during microvascular decompression operations.
AB  - Electromyographic (EMG) recordings from patients undergoing microvascular
      decompression (MVD) operations to relieve spasmodic torticollis were studied.
      When EMG potentials were recorded from the sternocleidomastoid muscle in response
      to electrical stimulation of the spinal accessory nerve (SAN) at the neck, an
      abnormal (delayed) response was seen in 9 of 12 patients who had unilateral
      symptoms. In 5 patients with bilateral symptoms, no such delayed response was
      seen. We assume that this abnormal muscle response depends on an abnormal cross
      transmission. Neural conduction time measurements, using electrical stimulation
      of the intracranial portion of the SAN, indicated that the location of this cross
      transmission was more central than the vascular compression of the SAN. We
      hypothesize that this location might be in the motonucleus of the SAN.
      Similarities between these abnormal EMG findings in patients with spasmodic
      torticollis and those reported earlier in patients with hemifacial spasm (HFS)
      are presented.

PMID- 8304079
TI  - Correlations between abnormalities on brain SPECT scan and interictal EEG-foci in
      children with 'intractable' partial epilepsy.
AB  - SPECT scanning with Tc99mHM-PAO was performed on 40 children with 'intractable'
      partial epilepsy; 27 patients had abnormalities on SPECT images consisting of
      areas of decreased cerebral blood flow. In 18 of these 27 subjects there was a
      good correlation between site of the abnormalities on SPECT scan and interictal
      EEG foci. 12 patients with regionally decreased CBF had also neuroimaging (C.T.
      and/or R.M.I.) abnormalities. The brain SPECT provides more precise detection of
      epileptogenic foci, when used to complement EEG, also in childhood-onset
      epilepsy.

PMID- 8304078
TI  - Ependymoma of the filum terminale: treatment and prognostic factors in a series
      of 28 cases.
AB  - A series of 28 ependymomas arising in the filum terminale was divided into two
      groups based on the presence/absence of connections with the conus medullaris
      and/or roots of the cauda equina. Group A comprised ependymomas having no
      connections with the contiguous structures and group B those either infiltrating
      or adhering to such structures. Factors having a positive influence on the
      prognosis (risk of recurrence) were: 1) clinical history under one year (p <
      0.01); 2) confinement of tumour to the filum terminale (p < 0.01); 3) total
      tumour removal (p < 0.05). Postoperative radiotherapy had no appreciable effect
      on outcome. The combination of significant factors was in turn significantly
      influenced by the mode of tumour growth, which proved to be the cardinal factor
      in prognosis. This point is examined in the light of the published work.

PMID- 8304080
TI  - Presence of papova-like viral particles in cerebrospinal fluid of AIDS patients
      with progressive multifocal leukoencephalopathy. An additional test for "in vivo"
      diagnosis.
AB  - An "in vivo" diagnosis of progressive multifocal leukoencephalopathy (PML), a
      neurological opportunistic viral infection in AIDS patients, can be made only by
      brain biopsy. In order to identify viral particles, we examined the cerebrospinal
      fluid (CSF) of 15 AIDS patients with focal neurological signs by electron
      microscopy using negative staining technique. In 2 out of 3 patients with
      clinical and neuroradiological presumptive diagnosis of PML, the CSF examination
      revealed papova-like viral particles. Our results support the hypothesis that the
      severe cell-mediated immunodeficiency reactivates papovavirus from a latent state
      in the brain, leading to PML. Therefore, the CSF study by negative staining might
      be a useful test for an "in vivo" diagnosis of PML.

PMID- 8304081
TI  - Acute primary meningoencephalitis from entamoeba Naegleria Fowleri. Report of a
      clinical case with a favourable outcome.
AB  - The Authors describe a primary amoebic acute meningoencephalitis case from
      Naegleria Fowleri, where the parasite was found in the cerebrospinal fluid and in
      culture. The case had a favorable outcome after treatment with amphotericin B.

PMID- 8304082
TI  - Acute meningitis from Cryptococcus neoformans (Filobasidiella neoformans) in a
      patient suffering from AIDS. Report of a clinical case with a favourable outcome.
AB  - The Authors describe a case of acute meningitis from Cryptococcus neoformans,
      with the finding of the fungus in the cerebrospinal fluid and in culture in a
      young subject with AIDS. The case had a favourable outcome after fluconazole
      treatment.

PMID- 8304083
TI  - A prevalence study of carotid atherosclerotic disease in patients aged above 60.
AB  - The results of Doppler sonography and the echotomographic evaluation of
      extracranial arteries performed on 139 asymptomatic patients aged above 60 are
      presented. Atheromatous lesions were found in 54 (38.85%) of the subjects, though
      most had no hemodynamic effects. Statistical analysis showed an increase in both
      number and gravity of lesions with advancing age in females alone. No significant
      association was found between risk factors and atheromatous lesions, except for
      smoking in males.

PMID- 8304084
TI  - Altered EEG pattern in aromatic hydrocarbon intoxication. A case report.
AB  - A case of acute intoxication after both cutaneous and inhalatory absorption of a
      mixture of organic solvents (toluene and benzene) is reported. The peculiarity of
      this case is represented by the abnormal EEG findings: paroxysmal slow waves at
      the beginning of the intoxication, persisting, although attenuated, days after
      the patient's complete recovery. Moreover, the fact that other investigations
      were normal gives further support to the significance of routine EEG recording in
      monitoring the involvement of CNS in cases of acute exposure to aromatic organic
      solvents.

PMID- 8304085
TI  - Role of viruses in the etiopathogenesis of multiple sclerosis.
AB  - Epidemiological studies performed to identify the possible cause of Multiple
      Sclerosis (MS) suggest that an environmental agent could be involved in its
      etiopathogenesis. For a long time it has been hypothesized that this agent was a
      virus, but until now no virus specific to MS has been consistently identified.
      Animal models indicate that the demyelination of the central nervous system can
      be induced by certain families of viruses, but the implication of this in the
      etiopathogenesis of MS has not been clearly demonstrated. Morbilliviruses were
      the most studied. Research on this subject arose from the observation of the
      similarity between the brain lesions occurring in MS and encephalitis caused by
      the measles virus (Subacute Sclerosing Panencephalitis). Antimeasles,
      antirubella, antiherpes zoster antibodies have been found in the blood and the
      cerebrospinal fluid of MS patients, but the relationship between this finding and
      the disease is not clear. It has recently been proposed that the pathogenetic
      immune response in the brain of MS patients might be directed predominantly
      towards antigens of a DNA virus, such as JCV. This preferentially infects glial
      cells and causes a demyelinating syndrome in immunodeficient subjects, called
      Progressive Multifocal Leucoencephalopathy. The target JC viral antigens in MS
      could be synthesized during transient viral reactivation. A recent hypothesis is
      that retroviruses may intervene in the etiopathogenesis of MS. Strong interest
      has been taken in HTLV-I after its identification in Tropical Spastic
      Paraparesis, a disease with certain similarities to MS. Serologic and polymerase
      chain reaction findings from various authors have suggested an association
      between this human retrovirus and MS. However more recent data are not consistent
      with this. Current experiments aimed at detecting retroviral particles in long
      term cultured peripheral blood monocytes and cerebrospinal fluid mononuclear
      cells in MS could clarify whether these cells provide a reservoir for such
      viruses, with a latency of many years without expression at brain level.

PMID- 8304086
TI  - [Biological and structural basis of the central nervous system plasticity].

PMID- 8304087
TI  - Gowland Hopkins Lectureship. Wolfgang Pfleiderer.

PMID- 8304088
TI  - Gowland Hopkins Lectureship. Edward C. Taylor.

PMID- 8304089
TI  - Natural pteridines--a chemical hobby.

PMID- 8304091
TI  - Progress in the study of biosynthesis and role of 7-substituted pterins: function
      of pterin-4a-carbinolamine dehydratase.

PMID- 8304090
TI  - Molecular cloning and recombinant expression of the human liver phenylalanine
      hydroxylase stimulating factor revealed structural and functional identity to the
      dimerization cofactor for the nuclear transcription factor HNF-1 alpha.

PMID- 8304092
TI  - Spectroscopic characterization of human liver pterin 4a-carbinolamine
      dehydratase.

PMID- 8304093
TI  - Is dihydropteridine reductase an anomalous dihydrofolate reductase, a flavin-like
      enzyme, or a short-chain dehydrogenase?

PMID- 8304094
TI  - Two crystal structures of rat liver dihydropteridine reductase.

PMID- 8304095
TI  - New inhibitors of dihydropteridine reductase (human brain).

PMID- 8304097
TI  - The spectrum of mutations in dihydropteridine reductase deficiency.

PMID- 8304096
TI  - cys-->ser mutations in ch-human dihydropteridine reductase.

PMID- 8304098
TI  - Drosophila GTP cyclohydrodrolase: multiple isoform products of a single gene
      derive from alternate transcripts that are developmentally regulated and
      functionally specific.

PMID- 8304099
TI  - Studies on GTP cyclohydrolase I of Escherichia coli.

PMID- 8304100
TI  - Partial purification and characterization of GTP cyclohydrolase I from spinach
      leaves.

PMID- 8304101
TI  - Detection and quantification of GTP cyclohydrolase I mRNA.

PMID- 8304102
TI  - Properties and reactions of pteridines carrying functionalised side chains at the
      3-position.

PMID- 8304103
TI  - Localization of GTP cyclohydrolase I (GTPCH) mRNA in the rat brain by in situ
      hybridization.

PMID- 8304104
TI  - Expression of GTP cyclohydrolase I (GTPCH) mRNA in the rat: tissue distribution
      and effect of reserpine.

PMID- 8304105
TI  - Regulation of tetrahydrobiopterin biosynthesis in cultured hypothalamic and
      mesencephalic neurons by cyclic AMP dependent GTP cyclohydrolase I gene
      expression.

PMID- 8304106
TI  - Mycophenolic acid simultaneously reduces intracellular GTP and
      tetrahydrobiopterin levels in neuro-2A cells.

PMID- 8304107
TI  - Human liver 6-pyruvoyl-tetrahydropterin synthase: expression of the cDNA,
      purification and preliminary characterization of the recombinant protein.

PMID- 8304108
TI  - Enzymatic properties of 6-pyruvoyl tetrahydropterin synthase purified from fat
      bodies of silkworm larvae.

PMID- 8304109
TI  - Northern blot analysis of sepiapterin reductase mRNA in mammalian cell lines and
      tissues.

PMID- 8304110
TI  - Purification and properties of human sepiapterin reductase from placenta.

PMID- 8304111
TI  - Stimulation of tetrahydrobiopterin synthesis by cytokines in human and in murine
      cells.

PMID- 8304112
TI  - N2-(N,N-Dimethylaminomethylene)-O4-(2-p-nitrophenylethyl)-biopterin: a versatile
      intermediate for a glycosidation reaction.

PMID- 8304113
TI  - Differential metabolism of tetrahydrobiopterin in monoamine neurons: a hypothesis
      based upon clinical and basic research.
AB  - This chapter has attempted to describe and integrate some of the clinical and
      basic research that support our hypothesis that the metabolism of BH4 is normally
      heterogeneous across different populations of monoamine-containing neurons. Based
      upon this hypothesis, there may now be reason to support the idea that certain
      neuropsychiatric illnesses, which are though to be the result (at least in part)
      of altered monoamine metabolism, might find their roots in an abnormal metabolism
      of BH4 within specific monoaminergic cell groups. Such a specific dysfunction
      might not be apparent in the rest of the brain or peripheral nervous system,
      thereby being difficult to detect. Perhaps the application of molecular
      biological techniques to studies of BH4 metabolism in man will shed new light on
      these problems.

PMID- 8304114
TI  - Tissue distribution of tetrahydrobiopterin generating enzymes.

PMID- 8304115
TI  - Long-term treatment of PC12 pheochromocytoma with dibutyryl cyclic AMP increases
      biopterin content in the cells but decreases that in the medium.

PMID- 8304116
TI  - Inter-relationships between pterins and cytokines produced during allogeneic
      immune reactions and possible use as early markers of immune activation.
AB  - The pterins neopterin and xanthopterin have been measured together with the
      cytokines IFN-gamma, TNF-alpha and TNF-beta in the supernatants of 20 allogeneic
      mixed lymphocyte reactions. We have calculated rank correlation coefficients
      between these analytes and the immune response. Our findings confirm that
      neopterin is a sensitive early marker of immune activation and show that another
      pterin, xanthopterin could be used likewise. Cytokine production was also
      proportional to immune activation but none could be used consistently as early
      markers of immune activation.

PMID- 8304117
TI  - An example of the detection of an esophageal carcinoma in its very early stage by
      urinary xanthopterin determination.

PMID- 8304118
TI  - Neopterin in subacute sclerosing panencephalitis.

PMID- 8304119
TI  - The synthesis of fluorine-containing pterins.

PMID- 8304120
TI  - The 7-deazaguanine derivative, queuine, regulates mammalian cell proliferation
      depending on the metabolic state.

PMID- 8304121
TI  - Tetrahydrobiopterin deficiency and an international database of patients.

PMID- 8304122
TI  - A microtitre plate method for measuring biopterin with cryopreserved Crithidia
      fasciculata.
AB  - The assay of biopterin derivatives in dried blood spots is used by us in initial
      screening for inherited defects in tetrahydrobiopterin synthesis. The previously
      described method (1) required aseptic technique and microbiological facilities.
      The modification detailed here has the advantages of antibiotic cover, which
      overcomes these needs and microtitre plate technology allowing the incubation
      time to be halved with precision and accuracy retained. Data reduction facilities
      may be applied.

PMID- 8304123
TI  - Oral administration of liposomally entrapped tetrahydrobiopterin.

PMID- 8304124
TI  - Experimental research on a fetal treatment for tetrahydrobiopterin deficiency.

PMID- 8304125
TI  - Experimental research on a new treatment for maternal phenylketonuria(PKU).

PMID- 8304126
TI  - Role of tetrahydrobiopterin in cytokine-stimulated metabolism of tryptophan and
      hydroxylation of arginine.

PMID- 8304127
TI  - Formation of FeIII or FeII complexes with acetylacetonate and 5,6,7,8
      tetrahydropterin as ligands and their activation of oxygen.

PMID- 8304128
TI  - 6R-L-erythro-5,6,7,8-tetrahydrobiopterin: a regulator of neurotransmitter
      release.

PMID- 8304129
TI  - Positron emission tomography studies on some neurotransmitter receptor systems
      with 6R-tetrahydrobiopterin pretreatment.

PMID- 8304130
TI  - Positron emission tomography (PET) study: the effects of 6R-L-erythro-5,6,7,8
      tetrahydrobiopterin (R-THBP, SUN 0588) on the central dopamine D1, D2 and D3
      receptors in rhesus monkey.

PMID- 8304131
TI  - Stereoelectronic effects in the autoxidative destruction of reduced folate
      derivatives.

PMID- 8304132
TI  - 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP, SUN 0588) acts on the brain
      muscarinic and nicotinic cholinergic receptors as evaluated by positron emission
      tomography (PET) in rhesus monkey.

PMID- 8304133
TI  - Effect of 6R-tetrahydrobiopterin on the central muscarinic cholinergic receptor
      as evaluated by positron emission tomography studies using rhesus monkey.

PMID- 8304134
TI  - Increase of tetrahydropterins in cell-free retinal extracts in response to light
      exposure.

PMID- 8304135
TI  - Effect of triamterene on the electroretinogram of Long Evans rats.

PMID- 8304136
TI  - Immunoenzymatic labeling of biopterin and neopterin in the pigment epithelium of
      bovine retina.

PMID- 8304137
TI  - Reduced pterins as scavengers for reactive oxygen species.

PMID- 8304138
TI  - Chemistry and biology of the molybdenum cofactors.

PMID- 8304139
TI  - Studies on the molybdenum cofactor. Synthesis of (+/-)-form B (dephospho).

PMID- 8304140
TI  - Molybdenum-pterin complexes: a functional and structural model for the binding
      site in the enzyme dimethyl sulfoxide reductase.

PMID- 8304142
TI  - Molybdopterin biosynthesis in man. Properties of the converting factor in liver
      tissue from a molybdenum cofactor deficient patient.

PMID- 8304141
TI  - Human molybdenum cofactor deficiency.

PMID- 8304143
TI  - Cloning of a eukaryotic molybdenum cofactor gene.

PMID- 8304144
TI  - Design and synthesis of inhibitors of folate-dependent enzymes as antitumor
      agents.

PMID- 8304145
TI  - Mindo/3 molecular-orbital calculations on the 6R-BH4 molecule and its metabolic
      precursors: conformation and activity.

PMID- 8304146
TI  - Synthesis and antitumor activity of LY288601, the 5,6-dihydro analog of LY231514.

PMID- 8304147
TI  - Synthesis and preliminary biological evaluation of analogues of 5,8
      dideazaisofolic acid and its 2-desamino-2-methyl derivative containing fluorine
      at position five.

PMID- 8304148
TI  - Synthesis and biological evaluation of analogues of 5,8-dideazaisofolic acid
      (IAHQ) modified at positions 2, 4 and 9.

PMID- 8304149
TI  - New thiophene substituted 10-deazaaminopterins: synthesis and biological
      evaluation.
AB  - Analogues of 10-deazaaminopterin (10-DAM) and 4-amino-4-deoxy-10-deazapteroyl
      gamma-methylene glutamic acid (MDAM) in which the benzene ring was replaced with
      a thiophene ring have been synthesized and evaluated for their antitumor
      activity. These analogues were N-([5-(2,4-diamino-6-pteridinyl)ethyl]-2-thenoyl)
      L- glutamic acid (1) and N-([5-(2,4-diamino-6-pteridinyl)ethyl]-2-thenoyl)-gamma
      meth ylene glutamic acid (2).

PMID- 8304150
TI  - Evaluation of the anti-arthritic activity and an alternate synthesis of a
      thiophene-substituted 10-deazaaminopterin.

PMID- 8304151
TI  - Lipophilic antifolates as candidates against opportunistic infections.

PMID- 8304152
TI  - Identification, stereoconfiguration, chromatographic and fluorescence properties
      of natural pterins.

PMID- 8304153
TI  - Analogues of classical antifolates bearing naphthoyl in place of benzoyl.

PMID- 8304154
TI  - Synthesis and biological activity of tricyclic, conformationally restricted
      analogs of lipophilic pyrido[2,3-d]-pyrimidine antifolates.

PMID- 8304155
TI  - Novel 2,4-diamino-5-substituted furo[2,3-d]-pyrimidines as potential antifolates.

PMID- 8304156
TI  - Bicyclic conformationally restricted analogs of nonclassical pyrido[2,3-d]
      pyrimidines as potential inhibitors of dihydrofolate reductases.

PMID- 8304157
TI  - Synthesis, structural and biochemical characterization of cytostatic methotrexate
      gamma-glutamyl-glutathione conjugates.

PMID- 8304158
TI  - Effect of a novel antifolate, N alpha-(4-amino-4-deoxypteroyl)-N delta
      hemiphthaloyl-L-ornithine (PT523), on growth of H35 rat hepatoma and HEPG2 human
      hepatoma cells.

PMID- 8304159
TI  - Tubulin binding properties of two chiral isomers with 1-deaza-7,8
      dihydropteridine structure.

PMID- 8304160
TI  - Effects of folic acid on pyrimethamine teratogenesis in rats.

PMID- 8304161
TI  - The mechanism of cofactor regeneration during phenylalanine hydroxylation.

PMID- 8304162
TI  - Mutations of human dihydrofolate reductase causing decreased inhibition by
      methotrexate.

PMID- 8304163
TI  - Conformational analysis of human dihydrofolate reductase inhibitor complexes:
      crystal structure determination of wild type and F31 mutant binary and ternary
      inhibitor complexes.
AB  - These structural studies reveal unusual intermolecular interactions for the
      binding of inhibitors and cofactor in ternary complexes with both wild type and
      F31 mutant recombinant human DHFR and show that these inhibitors have flexibility
      in occupying the active site. These studies also possibly indicate the first
      structural data for a ternary complex with a folate inhibitor and a polyglutamate
      side chain. However, further refinement of this data is necessary before this can
      be confirmed. In contrast to the ternary complexes of folate and MTX, the
      lipophilic antifolate PTX binds with its methoxybenzoyl ring oriented toward the
      cofactor nicotinamide ring, while that of TMQ it is bound closer to the Phe-31
      position. Furthermore, the nicotinamide ring makes a close contact to the N10
      amine of TMQ, significantly different from its binding site interactions in MTX
      complexes. These data also reveal that the conserved contacts between the
      cofactor carboxyamide with the enzyme backbone residues Ala-9 and Ile-16 are
      dictated by the enzyme and that changes in the orientation of the structural
      elements requires only subtle changes in the secondary structural units in which
      they are contained. Therefore, only by careful analysis of a series of enzyme
      complexes can the mechanisms of binding action be delineated.

PMID- 8304164
TI  - Computer-aided design of mechanism-based pterin analogues and MD/FEP simulations
      of their binding to dihydrofolate reductase.
AB  - Using a combined theoretical and experimental approach we have been able to
      predict several chemical properties and the contributions of the many factors
      which determine the macroscopic binding behaviour of these new mechanism-based
      compounds with DHFR, and also analyse experimental data to develop structure
      activity relationships.

PMID- 8304165
TI  - Does R67 dihydrofolate reductase possess a proton donor?

PMID- 8304166
TI  - Laser-sensitized tautomers in dihydrofolate reductase.

PMID- 8304167
TI  - Methotrexate-insensitive mutants of human dihydrofolate reductase (hDHFR)
      constructed by site-directed mutagenesis at phenylalanine 34.

PMID- 8304168
TI  - Kinetic investigation of methotrexate resistant human dihydrofolate reductase
      (hDHFR) mutants at Phe31.

PMID- 8304169
TI  - The effect of codon 31 on the relative affinities for the binding of designed 8
      alkyl-pterins to dihydrofolate reductase: a statistical perturbation theory and
      molecular dynamics simulation study.

PMID- 8304170
TI  - Effect of codon 22 mutations on substrate and inhibitor binding for human
      dihydrofolate reductase.

PMID- 8304171
TI  - Thermodynamic study of folate analogue binding to dihydrofolate reductases from
      different species.

PMID- 8304172
TI  - Comparison of binding and activity of 8-alkyl-pterins and 8-alkyl-N5-deaza
      pterins with dihydrofolate reductase.

PMID- 8304173
TI  - Development of a spectrofluorimetric method for determining the pKa of pterin
      analogue ligands bound to DHFR.

PMID- 8304174
TI  - Selective inhibition of dihydrofolate reductase from problem human pathogens.

PMID- 8304175
TI  - Translational regulation of the synthesis of dihydrofolate reductase.

PMID- 8304176
TI  - Expression of the trimethoprim resistant dihydrofolate reductase encoded by
      transposon TN4003 in a soluble form and its subsequent purification to
      homogeneity.
AB  - A high level expression in E. coli of the Tmpr type S1 DHFR was achieved by: (1)
      elimination of an internal start of translation within the RNA, and (2)
      optimization of gene expression by replacing nucleotides at the 5' end of the
      gene by nucleotides present in the highly expressible gene for SaDHFR. In
      addition, by replacing amino acids supposed to be on the surface of the protein,
      the mutein S1 DHFR[N48E,N130D] was constructed, which can be expressed in E. coli
      to high levels in a soluble and active form. The mutein S1 DHFR[N48E,N130D] was
      purified nearly to homogeneity. The enzyme is highly active and remains soluble
      even at a protein concentration of 10 mg/ml.

PMID- 8304177
TI  - Effect of genomic position on amplification of the DFR1 gene in Saccharomyces
      cerevisiae.

PMID- 8304178
TI  - Dihydrofolate reductase is not the target of trimethoprim in Saccharomyces
      cerevisiae.

PMID- 8304179
TI  - Point mutations in the dihydropteroate synthase gene causing sulfonamide
      resistance.

PMID- 8304180
TI  - Frequent amplification of a short chain dehydrogenase gene in methotrexate
      resistant Leishmania.

PMID- 8304181
TI  - Enzyme interactions involving T4 phage-coded thymidylate synthase and
      deoxycytidylate hydroxymethylase.

PMID- 8304182
TI  - Isolation of cDNAs encoding thymidylate synthase from soybean seedlings and
      expression of the protein in E. coli.

PMID- 8304183
TI  - Use of 10-propargyl-5,8-dideazafolate and directed mutagenesis to probe the
      catalytic mechanism of thymidylate synthase.

PMID- 8304184
TI  - Gamma-linked dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-
      dideazafolate as antitumour agents.
AB  - Our search for water-soluble quinazoline TS inhibitors that are transported into
      cells via the RFC, but are not substrates for FPGS, led us to the synthesis of
      dipeptide analogues of ICI 198583 diglutamate. Although a number of dipeptide
      analogues were active against isolated TS and L1210 cells in vitro, lack of in
      vivo stability was a problem. This was circumvented by the synthesis of modified
      dipeptides where either the alpha-carboxyl of the second amino acid was removed
      (alpha'-COOH) e.g. -L-glu-GABA or where the second amino acid was the unnatural D
      enantiomer e.g.-L-glu-D-glu. Further studies were performed with the -L-glu-D-glu
      and its 7-CH3, 2'F modified analogue, demonstrating that they use the RFC for
      cell entry but are not active through polyglutamate formation. The latter
      compound was tested against experimental tumour models and found to have good
      activity.

PMID- 8304185
TI  - Substituted-2-desamino-2-methyl-quinazolinones. A series of novel antitumour
      agents.

PMID- 8304186
TI  - Use of murine L5178Y lymphoma thymidine kinase mutants for in vitro and in vivo
      antitumour efficacy evaluation of novel thymidylate synthase inhibitors.

PMID- 8304187
TI  - Expression of wild type and mutant forms of human phenylalanine hydroxylase in E.
      coli.

PMID- 8304189
TI  - The duration of the inhibition of thymidylate synthase in intact L1210 cells
      exposed to two different classes of quinazoline analogues.

PMID- 8304188
TI  - Quinazoline antifolates inhibiting thymidylate synthase: synthesis of gamma
      linked peptide and amide analogues of 2-desamino-2-methyl-N10-propargyl- 5,8
      dideazafolic acid (ICI 198583).

PMID- 8304190
TI  - The toxicity of ICI D1694 in man and mouse.

PMID- 8304191
TI  - The interval between methotrexate and leucovorin determines the efficacy of 5
      fluorouracil modulation in vitro and in vivo.

PMID- 8304192
TI  - Potentiation of 5-fluorouracil induced inhibition of thymidylate synthase in
      human colon tumors by leucovorin is dose dependent.

PMID- 8304193
TI  - Interaction with 2(4)-thio-5-fluoro-dUMP of thymidylate synthases with differing
      sensitivities to 5-fluoro-dUMP.

PMID- 8304194
TI  - Mechanism of thymidylate synthase inhibition by N4-hydroxy-(N4-hydroxy-5- fluoro)
      dCMP in view of the structure and conformation of N4-hydroxy-(N4-hydroxy-5
      fluoro)-cytosine calculated by the AB initio quantum mechanical methods.

PMID- 8304195
TI  - Sulphonamide antifolates inhibiting thymidylate synthase: synthesis, enzyme
      inhibition and cytotoxicity.

PMID- 8304196
TI  - Folylpoly-gamma-glutamate synthetase.

PMID- 8304197
TI  - A re-examination of the metal requirement of Chromobacterium violaceum
      phenylalanine hydroxylase.

PMID- 8304198
TI  - Polyglutamate product formation by Lactobacillus casei folylpolyglutamate
      synthetase in vitro and in vivo in recombinant Escherichia coli.

PMID- 8304199
TI  - Development of a simple folylpolyglutamate synthetase assay in tissues and cell
      lines.

PMID- 8304200
TI  - Two novel HPLC methods which rapidly detect the substrates and cleavage products
      of gamma-glutamyl hydrolase.

PMID- 8304201
TI  - Purification and general properties of human folylpolyglutamate synthetase.

PMID- 8304202
TI  - Antitumor efficacy of classical non-polyglutamylatable antifolates that inhibit
      dihydrofolate reductase.

PMID- 8304203
TI  - Studies on the cross resistance of folylpolyglutamate synthetase-deficient,
      methotrexate-resistant CCRF-CEM human leukemia sublines.

PMID- 8304204
TI  - Histidines 138 and 143 are copper binding ligands in Chromobacterium violaceum
      phenylalanine hydroxylase.

PMID- 8304205
TI  - Variable pharmacodynamics of antifolates in squamous cell carcinoma of the head
      and neck.

PMID- 8304206
TI  - Evidence that 5-formyltetrahydropteroylglutamate has a metabolic role in one
      carbon metabolism.

PMID- 8304207
TI  - Cobalamin-dependent and cobalamin-independent methionine synthases in Escherichia
      coli: two solutions to the same chemical problem.

PMID- 8304208
TI  - Folate metabolites as modulators of antitumor drug activity.

PMID- 8304209
TI  - MTX does not affect enhanced biosynthesis and metabolism of S-adenosylmethionine
      in testosterone-induced hypertrophic mouse kidney.

PMID- 8304210
TI  - Thermolability of residual methylene-tetrahydrofolate reductase (MR) activity,
      methionine synthase activity and methyl-cobalamin levels in cultured fibroblasts
      from patients with MR deficiency.

PMID- 8304211
TI  - Enzymes for synthesis of 10-formyltetrahydrofolate in plants. Characterization of
      a monofunctional 10-formyltetrahydrofolate synthetase and copurification of 5,10
      methylenetetrahydrofolate dehydrogenase and 5,10-methenyltetrahydrofolate
      cyclohydrolase activities.

PMID- 8304212
TI  - Cloning of the genes encoding the serine hydroxymethyltransferases from
      Saccharomyces cerevisiae.

PMID- 8304213
TI  - Serine hydroxymethyltransferase: role of the active site lysine in the mechanism
      of the enzyme.

PMID- 8304214
TI  - Purification of Neurospora crassa cytosolic serine hydroxymethyltransferase.

PMID- 8304215
TI  - Purification and properties of rabbit liver 5,10-methenyltetrahydrofolate
      synthetase.

PMID- 8304216
TI  - Folate metabolism in pregnancy.

PMID- 8304217
TI  - Influence of gestation and lactation on the levels of plasma folates in sows.

PMID- 8304218
TI  - Identification of endogenous tetrahydrofolate and 10-formyltetrahydrofolate as
      major folates in rat bile.

PMID- 8304219
TI  - Development of a sensitive assay for detection of uracil in DNA.

PMID- 8304220
TI  - 5-methyltetrahydrofolate urinary excretion: modeling by cultured human kidney
      cells.
AB  - Initial attempts to model urinary folate reabsorption using cultures of HPT cells
      on porous filter inserts produced disappointing results in that large amounts of
      5M were transported across the epithelial monolayer in a nonspecific manner.
      Since the impermeable molecule inulin was also transported, there apparently
      existed a significant leakage pathway in the way that the cultured cells were
      used for transport studies. 5M was bound to the AP membrane and taken up into the
      HPT cell by specific processes, while inulin was excluded, suggesting that the
      HPT cells were nevertheless operating functionally. TER values from cultured HPT
      cells plateaued at a high level when cells became confluent, suggesting an
      epithelial layer with functional tight junctions. However, when growth media were
      removed and replaced with transport buffers, there was an immediate loss of TER
      that fully recovered if the transport buffers were preincubated for 60 min. Under
      these conditions, transport studies showed the expected results--no movement of
      inulin through the cell layer and much reduced transfer of folate through the
      paracellular pathway. These results suggest that a transient opening of tight
      junctions occurs when growth media are replaced with biological buffers (or with
      fresh growth media), but that recovery of tight junction function occurs with
      time.

PMID- 8304221
TI  - Contribution of plasma protein binding to the stability of tetrahydrofolate in
      pig plasma.

PMID- 8304222
TI  - Ligand induced conformation change in folate binding protein.

PMID- 8304223
TI  - The high-affinity folate binding protein in normal and malignant mammary gland
      tissue.

PMID- 8304224
TI  - Detergent-insolubility during the biosynthesis of membrane folate receptor-2.

PMID- 8304225
TI  - The reduced folate/methotrexate carrier and a membrane-associated folate binding
      protein as transport routes for novel antifolates: structure-activity
      relationships.

PMID- 8304226
TI  - Identification of a reduced folate/methotrexate carrier in human KB-cells
      expressing high levels of membrane associated folate binding protein.

PMID- 8304227
TI  - Altered transport of folic acid and antifolates through the carrier mediated
      reduced folate transport system in a human leukemia cell line resistant to (6R)
      5,10-dideazatetrahydrofolic acid (DDATHF).

PMID- 8304228
TI  - Transformation of an L-cell line with the DNA coding for the reduced
      folate/methotrexate transporter protein from a CCRF-CEM human leukemia cell line.

PMID- 8304229
TI  - Determinants of the disparate antitumor effects of (6R)5,10-dideaza-5,6,7,8-
      tetrahydrofolate and methotrexate toward methotrexate resistant CCRF-CEM cells,
      characterized by severely impaired antifolate membrane transport.

PMID- 8304230
TI  - Up-regulated transport of methotrexate and 5-methyl-tetrahydrofolate in a human
      breast cancer cell line.

PMID- 8304231
TI  - Glyceryl ether monooxygenase [EC 1.14.16.5]: stoichiometry and inhibition.

PMID- 8304232
TI  - The isolation and characterization of clones of 4a-hydroxytetrahydrobiopterin
      dehydratase.

PMID- 8304233
TI  - Receptors for transforming growth factor-beta.

PMID- 8304234
TI  - Biochemistry of B lymphocyte activation.
AB  - The activation of B lymphocytes from resting cells proceeds from the events of
      early activation to clonal proliferation to final differentiation into either an
      antibody-secreting plasma cell or a memory B cell. This is a complex activation
      process marked by several alternative pathways, depending on the nature of the
      initial antigenic stimulus. Over the past 5-10 years, there has been an explosion
      of studies examining the biochemical nature of various steps in these pathways.
      Some of that progress is reviewed here. In particular, we have described in
      detail what is known about the structure and function of the AgR, as this
      molecule plays a pivotal role in B cell responses of various types. We have also
      reviewed recent progress in understanding the mechanism of action of contact
      dependent T cell help and of the cytokine receptors, particularly the receptors
      for IL-2, IL-4, and IL-6. Clearly, all of these areas represent active areas of
      investigation and great progress can be anticipated in the next few years.

PMID- 8304235
TI  - MHC class I-deficient mice.
AB  - A great deal has already been learned from the analysis of beta 2m-mutant mice,
      but it is clear that a great deal remains to be learned. A significant (though
      unanticipated) problem with this model system is that it is functionally leaky:
      residual functional class I expression can be detected in beta 2m- mice, and
      small numbers of functional CD8+ lymphocytes are present in the animals. In many
      cases, this has frustrated the initial attempts at obtaining immediate definitive
      resolution of important questions regarding the function of class I molecules.
      This has occurred primarily in instances in which the class I-deficient mice fail
      to express an expected phenotype--for example, in studies showing that beta 2m-
      mice make adequate protective immune responses against certain intracellular
      pathogens, and are able to reject some allogeneic tissues with a relatively
      normal pace. On the other hand, it appears that combining the use of beta 2m-
      mice with other methods (for example, antibody-mediated depletion of CD8+ T
      cells) is usually adequate to circumvent these difficulties. It remains to be
      seen whether other better class I deficiencies can be engineered--for example,
      large deletions of class I genes or mutations in transcription factors essential
      for class I gene expression. The extent of immunocompetence of beta 2m- mice was
      somewhat surprising. It was widely expected that class I-deficient mice would be
      exquisitely sensitive to many viral infections, though the results indicate that
      sensitivity varies dramatically with the virus and conditions of infection.
      However, it appears that in lieu of one major arm of the immune system,
      compensatory immune mechanisms are in many cases able to deal with infection.
      Similar conclusions are developing from the analysis of several other recently
      generated mutant mice. Nevertheless, the results indicate a very important role
      for class I-directed responses in clearing infections mediated by various viral
      and parasitic agents, particularly in the case of more severe conditions of
      infection. Although the class I-deficient mice were initially considered
      primarily a vehicle for analysis of the role of CD8+ T cells, evidence is
      accumulating that they manifest deficiencies in several other types of
      lymphocytes, including NK cells, TCR alpha beta+CD4-CD8- cells, and a subset of
      TCR gamma delta+ cells. This has been a boon for analysis of the development of
      these cells, but at the same time it has created difficulties in assigning a
      biological effect of the mutation to a specific lymphocyte deficiency.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8304236
TI  - Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.

PMID- 8304237
TI  - Inflammatory responses induced by poly-L-arginine in rat lungs in vivo.
AB  - The inflammatory responses induced by the synthetic polycation poly-L-arginine
      injected either into the pleural cavity or into the trachea in rats have been
      investigated. Poly-L-arginine (4-40 nmol/rat) injected intrapleurally induced
      exudate formation and leucocyte migration (mainly polymorphonuclear cells). The
      exudate formation (but not cell migration) was dependent on the molecular weight
      of the poly-L-arginine used (24 and 115 kD). The poly-L-arginine-induced pleurisy
      was mainly dependent on activation of mast cells since it was significantly
      reduced either in rats depleted of their stores of histamine and serotonin or in
      rats previously treated with the serotonin receptor antagonist methysergide. The
      polyanions heparin and dermatan sulphate when administered intrapleurally with
      the polycation markedly reduced the exudate formation. Poly-L-arginine (115 kD,
      8.5 nmol/rat) injected intratracheally caused lung oedema, increased leucocyte
      number and protein content of bronchoalveolar lavage, respiratory insufficiency
      and 60% mortality in 6 h. Depletion of histamine and serotonin stores or of
      circulating neutrophils decreased the leucocytes in bronchoalveolar lavage but
      did not increase survival rate, whereas the polyanion dermatan sulphate prevented
      the mortality completely. These results suggest that the inflammatory changes
      caused by poly-L-arginine are dependent on mast cell activation but that the
      lethality after intratracheal administration is due to electrostatic interactions
      of the polycation with anionic surfaces present in the pulmonary epithelium.

PMID- 8304238
TI  - Role played by NK2 receptor and cyclooxygenase activation in bradykinin B2
      receptor mediated-airway effects in guinea pigs.
AB  - We have investigated the effects of SR-48968, an NK2 receptor antagonist, and
      indomethacin, a cyclooxygenase inhibitor, against bronchoconstriction and airway
      microvascular leakage induced by bradykinin (BK) in anesthetized guinea pigs. In
      addition, we have determined whether these effects were mediated via bradykinin
      B2 receptor activation, using a B2 receptor antagonist HOE 140. Lung resistance
      (RL) and extravasation of Evans blue dye into airway tissues were used as indexes
      of airway caliber and microvascular leakage, respectively. BK (15 nmol/kg i.v.)
      induced a significant increase in RL and leakage of dye at all airway levels,
      responses which were completely abolished by HOE 140 (0.13 mg/kg i.v.). SR-48968
      (1.5 mg/kg i.v.) had no effect against BK-induced airway effects. Indomethacin (5
      mg/kg i.v.) completely blocked the increase in RL and significantly inhibited the
      leakage of dye in peripheral intrapulmonary airway. In conclusion,
      bronchoconstriction induced by i.v. BK is mediated by release of cyclooxygenase
      products but not by stimulation of NK2 receptors, while the airway microvascular
      leakage only partly involves cyclooxygenase activation. Cyclooxygenase activation
      may occur following bradykinin B2 receptor stimulation.

PMID- 8304239
TI  - Differential effects of interleukin-1 alpha and beta on the arachidonic acid
      cascade in human synovial cells and chondrocytes in culture.
AB  - The effects of interleukin-1 alpha and beta were tested on the [3H]-arachidonic
      acid release and the prostaglandin synthesis by human cultured synovial cells and
      chondrocytes. Both forms of interleukin-1 stimulated the arachidonic acid release
      but interleukin-1 beta was more potent than IL-1 alpha. Human synovial cells and
      chondrocytes synthesized three types of prostaglandins upon stimulation with
      interleukin-1 alpha or beta: prostaglandin E2, F2 alpha and 6-keto-prostaglandin
      F1 alpha. Regarding the synthesis of these prostaglandins, IL-1 beta was again
      more potent than IL-1 alpha. A comparison between interleukin-1-stimulated
      synovial cells and chondrocytes revealed neither significant quantitative nor
      qualitative differences in both the arachidonic acid release and the
      prostaglandin synthesis.

PMID- 8304240
TI  - Involvement of protein kinase C in the control of microvascular permeability to
      colloidal carbon.
AB  - The vasculature of the rat small intestine and attached mesentery was perfused in
      vitro with a gelatin-containing physiological salt solution (GPSS). The inclusion
      of colloidal carbon (CC) in the perfusate towards the end of the experimental
      period enabled the "leakiness" of microvessels in the villi to be determined,
      since "leaky" vessels trap CC in their walls. Addition to the perfusate of the
      inflammatory agonists platelet-activating factor (PAF, 5 x 10(-6) M) or 5
      hydroxytryptamine (5-HT, 1 x 10(-4) M), or the microtubule-disrupting agents
      podophyllotoxin (5 x 10(-5) M), or colcemid (5 x 10(-5) M), or the protein kinase
      C (PKC) activator phorbol 12, 13-dibutyrate (PDB, 1 x 10(-6) M), caused
      significantly increased microvascular "blackening" as assessed by image analysis.
      4 alpha-phorbol 12, 13-didecanoate (PDD, 1 x 10(-6) M) had no effect.
      Pretreatment with the PKC inhibitor Ro 31-8220 [corrected] (1 x 10(-6) M)
      significantly reduced the effects of PAF, 5-HT and PDB, but not those of
      podophyllotoxin or colcemid. These results suggest, therefore, that PKC is
      involved in the permeability-enhancing effects of PAF, 5-HT and PDB. Pretreatment
      with indomethacin (1 x 10(-6) M) as a cyclooxygenase inhibitor did not reduce the
      response to PDB, indicating that prostaglandin release is of minor importance in
      the PDB-induced increase in microvascular permeability.

PMID- 8304241
TI  - A new assay for antiphlogistic activity: zymosan-induced mouse ear inflammation.
AB  - A new model of local inflammation has been developed: intradermal zymosan-induced
      mouse ear edema. The symptoms of inflammation induced by injecting zymosan into
      one of the ears were followed up for 72 h. The ear edema and the local
      accumulation of polymorphonuclear leukocytes' (PMN) marker enzyme,
      myeloperoxidase (MPO), were determined. Edema peaked at 4-6 h, while MPO activity
      peaked at 24 h after zymosan application. The correlation between inflammatory
      response and concentration of zymosan was also tested. Of the various
      concentrations tested, 1% suspension has been found optimal. Anti-inflammatory
      drugs and mediator antagonists were examined in order to establish the
      selectivity and sensitivity of the assay. A glucocorticoid (dexamethasone), two
      cyclooxygenase inhibitors (indomethacin, piroxicam) and an interleukin-1 (IL-1)
      release inhibitor (IX 207-887, Sandoz) all reduced edema and MPO activity as
      well. However, a lipoxygenase inhibitor (phenidone), a serotonin receptor
      antagonist (methysergide) and H1 and H2 receptor antagonists (clemastine and
      cimetidine, respectively) all failed to inhibit the reaction.

PMID- 8304242
TI  - Reduction of myocardial leukocyte accumulation and myocardial infarct size
      following administration of BAY u3405, a thromboxane A2 receptor antagonist, in
      myocardial ischaemia-reperfusion injury.
AB  - We investigated the effect of BAY u3405, a thromboxane A2 receptor antagonist in
      pentobarbital anaesthetized rats subjected to left main coronary artery ligation
      (1 h) followed by reperfusion (1 h; MI/R). Sham operated rats were used as
      controls (Sham MI/R). Survival rate, myocardial necrosis, myocardial
      myeloperoxidase activity (investigated as an index of leukocyte adhesion and
      accumulation) and serum creatine phosphokinase activity were studied. Ischaemia
      reperfusion injury significantly reduced the survival rate (45%), caused a marked
      myocardial necrosis, increased serum creatine phosphokinase activity (Sham MI/R =
      26 +/- 10.2 U/ml; MI/R = 213 +/- 19 U/ml) and produced a rise in myocardial
      myeloperoxidase activity in the area-at-risk and in the necrotic area (6.1 +/-
      0.4 U x 10(-3)/g tissue and 6.7 +/- 0.9 U x 10(-3)/g of tissue, respectively).
      The administration of BAY u3405 (30 and 60 mg/kg/i.v., 30 min before occlusion)
      significantly increased survival rate, lowered the area of myocardial necrosis,
      blunted the increase in serum creatine phosphokinase activity and reduced the
      increase in myeloperoxidase activity in both the area-at-risk and the necrotic
      area. Furthermore, the protective effect of BAY u3405 was dose-dependent. These
      data are consistent with an involvement of TXA2 in myocardial ischaemia
      reperfusion injury and suggest that BAY u3405 may represent a novel therapeutic
      approach to the treatment of acute ischaemia-reperfusion injury.

PMID- 8304244
TI  - Alterations in interleukin-6 production by LPS- and Con A-stimulated mixed
      splenocytes, spleen macrophages and lymphocytes in prenatally diazepam-exposed
      rats.
AB  - Prenatal exposure to diazepam leads to a suppression of mitogen or allogen
      induced lymphocyte proliferation as well as to a reduced production of tumour
      necrosis factor (TNF)-alpha from rat splenocytes during postnatal development of
      rats. We analysed the secretion of interleukin (IL)-6 which occurs at a later
      stage of the cytokine cascade. Splenocytes of male offspring from Long Evans
      rats, treated with a daily dose of diazepam (1.25 mg/kg) from gestational day 14
      to 20, were stimulated with lipopolysaccharide (LPS) and concanavalin A (Con A).
      In response to LPS, IL-6 liberation was significantly lower in mixed splenocytes
      and spleen macrophages of 2 and 8 week old prenatally diazepam-treated rats than
      in controls. Spleen lymphocyte preparations of prenatally treated animals
      exhibited a reduction of IL-6 release at 12 h and an increase at 24 h of
      incubation. At 2 weeks of age, Con A-induced IL-6 production could only be
      detected in mixed splenocytes; prenatally treated rats were releasing
      significantly less IL-6 than controls. In 8 week old rats, IL-6 liberation from
      mixed splenocytes and spleen macrophages was significantly lower in prenatally
      treated animals than in controls. Spleen lymphocytes presented a complex response
      picture depending upon incubation conditions. Our data indicate that in
      prenatally diazepam-exposed rats, the disturbance of cytokine release also
      extends to cytokines which play an important role in the later phases of immune
      responses.

PMID- 8304243
TI  - Ampiroxicam, an anti-inflammatory agent which is a prodrug of piroxicam.
AB  - Ampiroxicam is a nonacidic ether carbonate prodrug of piroxicam. Our results
      demonstrate that, in contrast to piroxicam, ampiroxicam does not possess
      detectable prostaglandin synthesis inhibitory activity in vitro. Ampiroxicam,
      however, has similar in vivo potency to piroxicam in suppressing paw swelling in
      rat adjuvant arthritis. In an acute model of paw inflammation in rats,
      ampiroxicam is less potent than piroxicam itself: the ED50's of ampiroxicam are 9
      and 3.5-fold higher than those of piroxicam following a single or multiple (5)
      daily oral doses, respectively. Using the phenylbenzoquinone stretching test as a
      method of evaluating acute analgetic activity, the ED50 for ampiroxicam is about
      3-fold higher than that of piroxicam. These tests of activity share the property
      of being partially prostaglandin-dependent. Ampiroxicam itself is not observed in
      plasma after oral dosing to man, nor in the rat, dog, and monkey as reported
      here. Bioavailability studies show that conversion to piroxicam is about 100%,
      90%, 70%, and 50% in these four species, respectively. These results indicate
      that ampiroxicam's anti-inflammatory activity is produced in vivo by conversion
      to piroxicam and support its credentials as an efficacious prodrug of piroxicam.

PMID- 8304245
TI  - Development of specific antibody and in vivo response to antigen in different rat
      strains: effect of dexamethasone and importance of endogenous corticosteroids.
AB  - Endogenous glucocorticoids undoubtedly play a role in the control of immune
      responses: their contribution to inter-strain variation is unknown. The
      development of specific IgG and IgE was measured following inoculation with
      ovalbumin in Lewis, Fischer, Wistar and Brown Norway rats. The Lewis gives a
      smaller IgG and IgE response than the other strains and the response in vivo to
      antigen injected into the paw correlates with the titre of specific antibody.
      Treatment with the steroid receptor antagonist RU486 (mifepristone) following
      inoculation reveals that in the Lewis, and to a lesser extent in the Brown
      Norway, the development of a specific IgG response is limited by endogenous
      corticosteroids. The IgG response in different strains is differently sensitive
      to treatment with the synthetic glucocorticoid dexamethasone, the Lewis being
      particularly resistant. The importance of control by endogenous corticosteroids
      should not be overlooked in contributing to strain differences in immune
      response.

PMID- 8304246
TI  - Inhibition of metalloproteinase activity of rheumatoid arthritis synovial cells
      by a new inhibitor [BE16627B; L-N-(N-hydroxy-2-isobutylsuccinamoyl)-seryl-L
      valine].
AB  - The effect of a new metalloproteinase (MP) inhibitor [BE16627B; L-N-(N-hydroxy-2
      isobutylsuccinamoyl)-seryl-L-valine, MW: 375.2] isolated from Streptomyces sp.
      was evaluated by using primary cultures of synovial cells from rheumatoid
      arthritis patients. BE16627B selectively inhibited MPs such as human stromelysin
      and 92 kD gelatinase. After the cells were cultured with BE16627B for 5 days,
      BE16627B inhibited MP activity in the primary culture supernatants from synovial
      cells in a dose-dependent fashion without showing apparent cytotoxicity or
      affecting the production and secretion of MPs. Its IC50 for active collagenolysis
      before activation by trypsin was 25 microM.

PMID- 8304247
TI  - Effect of etodolac on type-II collagen-induced arthritis in mice.
AB  - We tested the effect of etodolac on the development of type-II collagen-induced
      arthritis in DBA/1J mice. It was administered orally once daily for 35 days after
      the primary immunization with type-II collagen. Etodolac (10 mg/kg) significantly
      inhibited the development of signs of arthritis on day 28 to day 35. Indomethacin
      (1 mg/kg) also significantly inhibited it on day 29 to day 34. Radiographic
      examination showed that etodolac (10 mg/kg) significantly prevented the
      development of osteopenia, bone erosion and new bone formation of the joints on
      day 35, while indomethacin (1 mg/kg) significantly prevented only the development
      of bone erosion. Histopathological examination showed that both etodolac (10
      mg/kg) and indomethacin (1 mg/kg) significantly prevented the development of
      synovitis, erosion of cartilage of the joints and bone destruction of the limbs
      on day 35. Etodolac and indomethacin did not affect the serum level of anti-type
      II collagen antibodies. These results suggest that etodolac and indomethacin
      suppress type-II collagen-induced arthritis without affecting humoral immune
      responses.

PMID- 8304250
TI  - Autoimmune diseases: immunogenetic mechanisms and strategies for therapy.

PMID- 8304249
TI  - Is copper pro- or anti-inflammatory? A reconciling view and a novel approach for
      the use of copper in the control of inflammation.
AB  - The anti-inflammatory role of copper is well-known although still largely
      unexplained. On the other hand, the capacity of copper to induce the formation of
      damaging .OH radicals in vivo is no longer debated. These two aspects of the
      physiological activity of copper have been considered to be paradoxical.
      Arguments developed here show that they may actually derive from a single
      chemical process, the type of physiological effect observed depending on the
      ligand bound to the copper ions involved in Fenton chemistry. Both iron and
      copper are Fenton catalysts. Given its intrinsic coordination properties,
      however, copper induces more site-specific .OH damage to the ligands bound to it.
      It, therefore, appears that copper complexes with specific .OH-inactivating
      ligands (OILs) can be used as "lures" for the Fenton reaction, .OH radicals
      preferentially formed on these being immediately inactivated. The hypothesis is
      thus put forward here that copper-OIL complexes acting as effective Fenton
      catalysts are potential "catalase-like" anti-inflammatory drugs.

PMID- 8304251
TI  - AAFP establishes an HIV 'warm line' to assist physicians.

PMID- 8304252
TI  - Preventing group B streptococcal sepsis in the newborn.

PMID- 8304248
TI  - Copper and zinc body levels in inflammation: an overview of the data obtained
      from animal and human studies.
AB  - The development of acute and chronic inflammatory processes induces, in the
      laboratory animal, a net accumulation of both copper and zinc in many body
      compartments, the inflamed area included. In rheumatoid arthritis, as well as in
      animal models, only plasma zinc concentration seems to be significantly
      correlated with disease severity, while the increase in total plasma copper could
      be described as an "all or nothing" phenomenon. Moreover, in rheumatoid
      arthritis, it appears that the disease develops and progresses without being
      linked to either copper or zinc deficiency conditions. Thus, it seems reasonable
      to suggest that a rationale for the use of copper and/or zinc in the treatment of
      inflammatory disorders can only be drawn from the intrinsic pharmacological
      properties of such trace elements, rather than from the need for their repletion.

PMID- 8304253
TI  - Prevention in clinical practice.

PMID- 8304254
TI  - The family physician's role in keeping parents involved in their adolescents'
      lives.

PMID- 8304255
TI  - Use of a hair pick to stabilize rolling veins.

PMID- 8304256
TI  - High suicide rate in elderly white men.

PMID- 8304257
TI  - Improved criteria for selecting physicians for HMOs and PPOs.

PMID- 8304258
TI  - Family-centered birthing.

PMID- 8304259
TI  - The fusiform excision.
AB  - The fusiform excision of a skin lesion is a common procedure in outpatient care.
      The appearance of the final scar is improved by orienting the excision parallel
      to resting skin tension lines with at least a 3:1 length-to-width ratio,
      undermining the lateral wound edges and using absorbable subcuticular sutures. A
      properly designed fusiform excision can be closed primarily and infrequently
      results in the formation of excessive mounds of tissue at the wound ends, known
      as "dog-ears."

PMID- 8304260
TI  - Sleep apnea.
AB  - The diagnosis of sleep apnea should be considered when a patient complains of
      snoring and excessive daytime somnolence. Middle-aged obese men are at particular
      risk, although apnea can occur in women and the elderly, as well as in persons
      who are not obese. An overnight polysomnographic sleep study can reveal the
      degree and type of apnea. Effective medical therapy can provide prompt clinical
      improvement. General treatment measures include weight loss and, in mild cases,
      training the patient to sleep in a side-lying position. Continuous positive
      airway pressure administered by masks worn at night is especially effective.
      Surgical treatment can help properly selected patients.
      Uvulopalatopharyngoplasty, which increases the volume of the oropharynx, requires
      follow-up polysomnographic studies. Tracheostomy is extremely effective and can
      be lifesaving in severe obstructive apnea. Effective therapeutic options make
      early recognition and treatment of this disorder vital and successful.

PMID- 8304261
TI  - Management of chronic constipation in infants and toddlers.
AB  - Infants and toddlers with constipation usually have a history of infrequent, hard
      and painful bowel movements, often accompanied by screaming and stool-holding
      maneuvers. Encopresis, the intermittent and involuntary passage of formed-to
      liquid feces, is common. Although constipation most often has a functional cause,
      the history and physical examination should rule out anatomic, endocrinologic,
      metabolic or neurologic causes. Hirschsprung's disease--aganglionic megacolon--is
      a congenital cause of severe constipation that occurs in one of every 5,000
      births. Treatment consists of fecal disimpaction, laxatives to prevent future
      impaction, promotion of regular bowel habits and, finally, toilet training.
      Parents should be reassured that although this disorder is not life-threatening,
      several months to years of supportive intervention may be required for effective
      treatment.

PMID- 8304262
TI  - Mucocutaneous manifestations of chancroid, lymphogranuloma venereum and granuloma
      inguinale.
AB  - The sexually transmitted diseases chancroid, lymphogranuloma venereum and
      granuloma inguinale should be familiar to physicians who care for patients at
      risk. The mucocutaneous manifestations of these three diseases must be
      distinguished from the lesions of other venereal diseases, such as primary
      syphilis and genital herpes simplex. Human immunodeficiency virus (HIV) infection
      should always be considered in patients with any venereal disease, since sexually
      transmitted diseases often occur together. Furthermore, the genital erosions that
      occur in patients with these three disorders may predispose them to HIV
      infection.

PMID- 8304263
TI  - Malignant external otitis: a case report and review.
AB  - Malignant external otitis is an unusual but serious and potentially fatal
      condition that has only recently been described. It is an invasive pseudomonal
      infection of the external auditory canal and deep periauricular tissues that
      characteristically involves the bone and adjacent cartilaginous structures, and
      it may lead to osteomyelitis of the base of the skull. It typically occurs in
      elderly diabetic patients. Malignant external otitis can cause severe pain,
      necrosis of the external auditory canal and progressive palsies of the facial and
      cranial nerves. Treatment consists of debridement of external auditory canal
      granulation tissue and long-term therapy with an antipseudomonal cephalosporin or
      an antipseudomonal penicillin plus an aminoglycoside.

PMID- 8304264
TI  - Group B streptococcal disease in the perinatal period.
AB  - Group B streptococcus is the major cause of neonatal sepsis in the United States.
      It is estimated that 2,000 infants die annually of syndromes related to group B
      streptococcus infection. In the early-onset syndrome, transmission is from mother
      to child, either in utero or during birth. Pneumonia is the most common
      presentation in infants who develop symptoms during the first seven days of life.
      The principal manifestation of late-onset infection is meningitis, which occurs
      in 85 percent of this group. Although group B streptococcus infection is normally
      remediable with penicillin therapy, rapid diagnosis and treatment are necessary
      to prevent the serious consequences of the disease. A vaccine is under
      development, although the cost-effectiveness of a widespread immunization program
      for a disease with such a low frequency is still unknown. The potentially serious
      outcomes of this infection, however, make it a major problem for physicians
      involved in neonatal care.

PMID- 8304265
TI  - Evaluation of a breast complaint: is it cancer?
AB  - The most common breast complaints are nipple discharge, breast pain and a breast
      mass. These problems can be evaluated in a step-wise manner to determine whether
      the etiology is cancer. A breast mass is the most common symptom of cancer, but
      breast pain and nipple discharge also must be evaluated carefully. The history
      and physical examination, needle aspiration, mammography, ultrasound examination
      and biopsy are useful in determining the underlying cause of the problem.

PMID- 8304266
TI  - ACIP releases recommendations on the combined DTP and Hib vaccine. Advisory
      Committee on Immunization Practices.

PMID- 8304267
TI  - Incidence of HIV infection.

PMID- 8304268
TI  - A new treatment for multiple sclerosis.

PMID- 8304269
TI  - Pharmaceutical care in an ambulatory care center.

PMID- 8304270
TI  - Pharmacists' role in preventing and treating HIV infection.

PMID- 8304271
TI  - Why I like the Coordinated Care Network idea.

PMID- 8304272
TI  - Case study: keeping confidences.

PMID- 8304273
TI  - Barriers to providing cognitive services.
AB  - Seventy-three pharmacists were surveyed to evaluate their perceptions of barriers
      to performing cognitive services in community pharmacy; 64 responded. Perceived
      barriers to counseling patients were excessive workload, lack of privacy, patient
      attitudes, and store layout. Perceived barriers to interacting with physicians
      were difficulties contacting them, negative physician attitudes toward
      pharmacists' recommendations, excessive workload, and inadequate patient
      information. Rates of interaction with prescribers correlated with greater job
      satisfaction; rates of patient counseling did not. Methods to address these
      barriers include structuring reimbursement and workload around cognitive services
      rather than drug product dispensing, redesigning pharmacies to provide counseling
      areas, changing attitudes and abilities through pharmacist education, and using
      technology to promote information transfer between pharmacies and health care
      facilities.

PMID- 8304274
TI  - Drugs do not cause infections.

PMID- 8304275
TI  - The effect of evaporative cooling of respiratory protective devices on skin
      temperature, thermal sensation, and comfort.
AB  - High skin temperature of the face is a major source of discomfort while wearing
      respiratory protective devices. In this paper theoretical considerations of
      thermal exchange between the face and the environment with and without a mask are
      discussed to elucidate factors that may improve the design of masks to increase
      their acceptability. Comfort thresholds have been related to skin temperature for
      both resting and exercising subjects. Skin temperature below 34.5 degrees C at
      rest, and 31 degrees C during exercise, is rated as comfortable. In a previous
      study it was determined that evaporative cooling could reduce skin temperature
      and decrease discomfort in a dummy mask. In the present study evaporative cooling
      of a more sophisticated dummy mask and a modified Scott model 66 twin-cartridge
      respirator was tested in resting and exercising subjects. Skin temperature was
      significantly reduced when wet felt covered the surface of both masks and at rest
      the masks were rated as significantly more comfortable than with dry felt on the
      outer surface. It is concluded that evaporative cooling of an existing face mask
      can reduce skin temperature to the comfort threshold in resting subjects. Data
      suggest that similar results are attainable for exercising subjects.

PMID- 8304276
TI  - The effect of respirator dead space and lung retention on exposure estimates.
AB  - This paper develops, tests, and applies equations that predict the magnitude of
      the effect of lung retention and respirator dead space on average inhalation
      concentration and other related quantities. The equations were validated by
      numerical simulation and experimental measurement with a respirator on a
      mannequin connected to a breathing machine. Experimental data are presented
      verifying the applicability of the equations. The authors present applications of
      the equations and procedures to various types of respirator performance
      measurements and to a predictive respirator performance model. Graphs are
      presented giving correction factors. In all cases the correction factors are less
      than 2. Under typical conditions of workplace protection factor measurement with
      half-mask respirators, average inhalation concentration will be 105% to 125% of
      full-cycle average concentration.

PMID- 8304277
TI  - A proposal for improving the role of exposure modeling in risk assessment.
AB  - This paper explores the adequacy of using currently available exposure assessment
      models for indoor air inhalation exposures in the context of the uncertainty that
      exists in both the dose-response assessment and the exposure assessment. A tiered
      system is proposed for implementing exposure assessments. Each tier involves
      additional research, but also would lead to reductions in uncertainty. The
      authors discuss a possible comprehensive research program that will permit the
      building of well-validated models for indoor air inhalation exposures among
      classes of chemicals, building types, and exposure scenarios. The authors believe
      that until such a research program is undertaken, modeling of exposures (and
      therefore risks) using the current, unvalidated modeling approaches provides
      little more than worst-case estimates that are useful primarily for making
      screening decisions about risks.

PMID- 8304278
TI  - Evaluation and control of worker exposure to fungi in a beet sugar refinery.
AB  - A study of worker exposure to airborne fungi was undertaken in a sugar beet
      refinery to evaluate the level of exposure and to determine if controls could be
      implemented that would lower these exposures. A previous study at this refinery
      identified one worker who reacted on challenge testing to the moldy but not the
      fresh sugar beet pulp, had specific Immunoglobulin G to Aspergillus niger, and
      specific Immunoglobulin E to Aspergillus. Also, two employees were diagnosed with
      occupational asthma. In the study reported here, two field surveys were
      conducted, the first during the sugar production campaign (January) and the
      second during postproduction cleanup and maintenance (June). Approximately 65
      personal and area air samples were collected on polycarbonate filters and the
      culturable fungal spores were identified and enumerated. This study showed high
      exposure of pellet loaders and pellet silo workers to various species of
      Aspergillus. Other fungal species that might pose a health hazard were detected.
      Exposures to fungi during the postproduction cleanup and maintenance phase were
      much higher than those measured during the production campaign. Engineering
      controls that would reduce employee exposure are discussed.

PMID- 8304279
TI  - Respirator mask design modules and their interactions.
AB  - The respirator performance rating table (PRT) scheme has been offered as a way to
      organize physiological information to be useful for mask design. Designers do not
      usually deal exclusively with one kind or another of mask physiological effect.
      This paper presents normal mask design modules and how they relate to mask
      physiological effects as given in the PRT.

PMID- 8304280
TI  - Abdominal belts in industry: a position paper on their assets, liabilities and
      use.

PMID- 8304281
TI  - Energy metabolism during pregnancy: influence of maternal energy status.
AB  - Additional energy requirements for term pregnancies are traditionally estimated
      as 1200 kJ/d or 325 MJ. These estimates approximate measured energy costs for
      well-nourished women, but non-Western populations subsisting on limited diets
      have much lower expenditures. Based on recent studies of energy expenditure
      during pregnancy, this paper reviews the 1) association between gestational
      weight gain and fat gain, 2) the influence of maternal energy status on basal
      metabolic energy expenditure in late pregnancy, and 3) potential energy
      metabolism adaptations available to pregnant women and how adaptations vary with
      energy status. Available data suggest that additional energy requirements during
      pregnancy vary from 0 to 500 MJ and depend on maternal energy status. If energy
      supplies are limited, adaptations spare energy for fetal growth; if energy is
      abundant, energy balance may be achieved in different ways depending on
      individual behavioral changes in food intake or activity patterns and on
      adjustments in basal metabolism or fat deposition.

PMID- 8304282
TI  - Effects of dieting and physical activity on pregnancy and lactation.
AB  - Concerns regarding weight control and fitness during the reproductive years have
      prompted questions about dieting and physical activity among pregnant and
      lactating women. Dieting to lose weight is never recommended during pregnancy,
      even among obese women. Once lactation is established, moderate energy
      restriction to achieve a weight loss of < or = 2 kg/mo is probably safe for women
      who are overweight initially. There are several potential risks and benefits of
      exercise during pregnancy and lactation. The data available indicate that
      moderate aerobic exercise is safe and beneficial for most women, if appropriate
      guidelines are followed.

PMID- 8304283
TI  - Benefits and risks of modifying maternal fat intake in pregnancy and lactation.
AB  - The National Cholesterol Education Program recommends that healthy Americans aged
      > 2 y reduce energy intake to maintain ideal body weight, saturated fat to 10% of
      energy, fat intake to 30% of energy, and cholesterol consumption to < 300 mg/d.
      Although these guidelines exclude pregnant or lactating women, nursing infants,
      and very young children, women with gestational diabetes, preeclampsia, and
      familial hyperlipidemias may benefit from them. In a normal pregnancy, serum
      cholesterol and triglycerides rise 25-40% and 200-400%, respectively. Multiparous
      middle-aged women may have an increased incidence of angina and cholesterol
      gallstones from the hypercholesterolemia of pregnancy. Few studies support the
      safety of maternal low-fat diets for the developing fetus or demonstrate benefits
      to the mother. Polyunsaturated fatty acids lower serum lipids, and n-3 fatty
      acids may improve some obstetric complications. Arachidonic acid (20:4) and
      docosahexaenoic acid (22:6) may benefit the psychomotor and visual development of
      children.

PMID- 8304284
TI  - Nutritional consequences of chronic maternal conditions during pregnancy and
      lactation: lupus and diabetes.
AB  - Few treated chronic conditions preclude the ability of a mother to conceive.
      However, consequences of the condition may undermine the pregnancy or aggravate
      maternal disease. Most chronic conditions require nutritional intervention beyond
      the normal needs of pregnancy. Insulin-dependent diabetes mellitus (IDDM) and
      systemic lupus erythematosus (SLE) are two common autoimmune disorders that
      affect women of childbearing age. Little has been published about the long-term
      consequences of current medication regimens for SLE and their interactions with
      either nutrient metabolism or requirements. More information is available on
      macronutrient dietary needs and metabolism during pregnancy and lactation in
      women with IDDM, but little is published about the metabolism of other nutrients
      in this condition. Thus, the nutritional consequences of treating these diseases
      during pregnancy and lactation must be evaluated continually.

PMID- 8304285
TI  - Maternal calcium requirements during pregnancy and lactation.
AB  - Recommendations for calcium intakes during pregnancy and lactation differ around
      the world, reflecting the inadequacy of knowledge about calcium requirements in
      human reproduction. In theory, insufficient calcium supply during pregnancy and
      lactation could result in maternal bone loss, reduced breast-milk calcium
      secretion or impaired infant bone development. However, although calcium intakes
      vary widely, no specific problems associated with dietary calcium deficiency have
      been identified. Alterations in absorption, metabolism, and excretion may
      conserve calcium when requirements increase. Bone changes have been observed in
      pregnancy and lactation, but the relationship with diet is unknown. Similarly,
      the effects of maternal calcium intake on breast-milk calcium and infant bone
      growth are not understood. Calcium salts (1-2 g Ca/d) may reduce hypertensive
      disorders in pregnancy, but the role of dietary calcium needs exploration. More
      research is required before we can be confident about advising women to increase
      their calcium intakes during pregnancy and lactation.

PMID- 8304286
TI  - Do North American women need supplemental vitamin D during pregnancy or
      lactation?
AB  - Studies in European and other countries have shown that vitamin D deficiency
      during pregnancy may adversely affect fetal growth, bone ossification, tooth
      enamel formation, and neonatal calcium homeostasis. Whether effects of vitamin D
      deficiency on pregnant or lactating mothers differ from effects observed in
      nonpregnant or nonlactating women is not clear. Poor maternal vitamin D status
      during lactation results in low breast-milk vitamin D. However, human milk
      usually contains small vitamin D amounts and, under normal circumstances, the
      sunshine exposure of human-milk--fed infants is the major factor affecting their
      vitamin D status. Mothers at risk of vitamin D deficiency are those who avoid
      dairy products, which are routinely vitamin D fortified, and live in more
      northern latitudes. Dark-skinned women also are theoretically at risk of vitamin
      D deficiency. Sunshine exposure is a major vitamin D source, and given adequate
      exposure, supplemental vitamin D is not necessary. However, defining adequate
      sunshine exposure is difficult.

PMID- 8304287
TI  - Anemia and iron-deficiency anemia: compilation of data on pregnancy outcome.
AB  - Anemia diagnosed early in pregnancy is associated with increased risks of low
      birth weight and preterm delivery. In several studies, the association between
      anemia and outcomes reversed direction during the third trimester; maternal
      anemia was no longer a risk factor for poor pregnancy outcomes. Camden study data
      were used to examine the probable cause of this observation. Maternal iron
      deficiency anemia, diagnosed at entry to prenatal care, was associated with low
      dietary energy and iron, inadequate gestational gain, and twofold or greater
      increases in the risks of preterm delivery and low birth weight. During the third
      trimester, these associations (except with inadequate gestational gain) were no
      longer present. This reversal of risk status may be attributable to the poor
      predictive value of anemia and iron deficiency tests during the third trimester.
      However, the relationship between poor diet (with inadequate iron intake) and
      increased likelihood of preterm delivery persisted during the third trimester.

PMID- 8304288
TI  - Iron deficiency: assessment during pregnancy and its importance in pregnant
      adolescents.
AB  - The assessment of iron deficiency in pregnancy requires the accurate
      determination of indicators that have significant within-subject variability. For
      instance, serum ferritin concentrations may vary by as much as 25% from one day
      to the next. Added to this uncertainty about biological variability is the
      influence of plasma volume expansion on concentration-dependent indexes such as
      ferritin, plasma iron, and hemoglobin. Multiple measurements of iron status are
      suggested, and, if this is not possible, within-subject variability needs to be
      included in the confidence of assigning individuals to iron-status groups. An
      example of this former approach is shown for a group of pregnant adolescents with
      a very high prevalence of iron deficiency. Although the assessment of iron status
      in human populations is advanced compared with that of other nutrients, there is
      still a large uncertainty about absolute diagnosis during pregnancy.

PMID- 8304289
TI  - Periconceptional folate and neural tube defect.
AB  - The US Public Health Service recommends that all women in the United States who
      might possibly become pregnant should consume 0.4 mg folic acid/d to lower the
      incidence of neural tube defect (NTD). This paper reviews the bases for this
      recommendation: controlled trials of periconceptional folate, observational
      studies of folate supplementation, studies relating dietary folate to NTD, a
      trial of dietary education aimed at lowering the rate of NTD, and studies of the
      relationship to NTD of serum and red blood cell folate concentrations. It remains
      unclear that trials to prevent recurrent NTD apply directly to occurrent NTD, and
      the minimum necessary dose of folate is unknown. Given the potential dangers of
      high levels of folate in the general diet, particularly the masking of the
      hematologic effects of vitamin B-12 deficiency in elderly persons, with the
      consequent possibility of vitamin B-12 deficiency presenting as severe,
      irreversible neurologic disease, it is suggested that, until the impact of
      increasing the general folate level of the diet is better understood, tablet
      supplementation of folate to women of child-bearing age is preferable as an
      interim measure to increased food fortification.

PMID- 8304290
TI  - Maternal vitamin A status and its importance in infancy and early childhood.
AB  - Early fetal vitamin A supplies must be regulated to avoid teratogenic
      consequences from too little or too much. Late in gestation, adequate maternal
      vitamin A status is important for newborn reserves and for sustaining adequate
      breast-milk concentrations. Vitamin A supplements are not needed for most
      pregnant women in Western countries who consume the recommended dietary allowance
      during their reproductive years. Increased consumption of vitamin A-rich foods
      can meet increased needs during lactation. Women in developing countries whose
      habitual intakes are near basal needs should receive an additional 100 micrograms
      retinol equivalents (RE) during pregnancy and 300 micrograms RE during lactation.
      Supplements not above 3000 micrograms RE (10,000 IU) daily are safe for fertile
      women where circumstances preclude obtaining the needed increment through diet.
      The first postpartum month is the only safe period during which to provide
      deficient lactating women with a single high-dose supplement to benefit the
      mother and breast-feeding infant for several months.

PMID- 8304291
TI  - Promoting positive nutritional practices during pregnancy and lactation.
AB  - This paper describes three key elements for promoting positive nutrition
      practices among women during pregnancy and lactation: 1) increasing access to
      prenatal care; 2) redirecting the content of prenatal care to include a greater
      emphasis on screening and intervention for behavioral risk factors, including
      poor nutritional practices; and 3) delivering nutritional care based on recent
      Institute of Medicine guidelines. These guidelines advise the practitioner to
      determine prepregnancy body mass index (BMI) and to recommend different weight
      gains during pregnancy according to BMI category, to assess dietary and lifestyle
      factors to determine the need for nutrient supplements and to base the supplement
      composition on the nature of the nutritional need identified, to provide routine
      supplementation of only 30 mg iron beginning in the second trimester of
      pregnancy, and to base the diagnosis of anemia on different cutoff values by
      stage of pregnancy and smoking status.

PMID- 8304293
TI  - A new classification system for acute pancreatitis.

PMID- 8304292
TI  - Should vitamin-mineral supplements be recommended for all women with childbearing
      potential?
AB  - Interest in maternal nutritional status as a critical factor for prenatal
      development has increased. When supplemented before conception, iodine prevents
      cretinism and folic acid reduces neural tube defect risks. Other nutrient
      supplements may also reduce pregnancy complications. Thus, should supplements be
      advocated for all women with childbearing potential? Potential supplementation
      benefits include 1) improved nutritional status, 2) reduced risk of some
      developmental defects, 3) improved antioxidant and immune defense systems, 4)
      lower incidence and/or slower progression of some diseases, and 5) harmonization
      of government and health care professionals' dietary recommendations for optimal
      health. Potential questions are, will the supplement reduce a woman's motivation
      to maintain and/or improve dietary quality? Will the supplement result in
      excessive nutrient intakes and/or adverse nutrient-nutrient interactions? Will
      supplement use encourage the perception that all women are, by definition, well
      nourished? These issues should be clarified before widespread supplementation
      programs are implemented.

PMID- 8304294
TI  - Meconium ileus equivalent in children and adults.

PMID- 8304295
TI  - Biofeedback as a treatment approach to gastrointestinal tract disorders.

PMID- 8304296
TI  - Barrett's esophagus after cardiomyotomy for esophageal achalasia.
AB  - Heller's myotomy for esophageal achalasia was performed on 64 patients in the 24
      yr up to 1988. After follow-up averaging 13 yr, 46 patients were reexamined with
      endoscopy, biopsy, and manometry. Barrett's metaplasia of the distal esophagus
      was found in four patients 6, 13, 20, and 23 yr after the myotomy. These four
      also underwent ambulatory 24-h pH monitoring. They had the lowest distal
      esophageal sphincter pressures (1-5 mm Hg), and all four had symptoms of
      gastroesophageal reflux and pathologic pH values (< 4 in the distal esophagus for
      32-62% of the total recording time). Because of heightened risk for the
      development of Barrett's metaplasia following cardiomyotomy for esophageal
      achalasia, with increased liability to carcinoma of the esophagus, regular
      endoscopic surveillance of these patients is advisable.

PMID- 8304297
TI  - Analysis of hepatic vein waveform by Doppler ultrasonography in 100 patients with
      portal hypertension.
AB  - OBJECTIVES: We classified the Doppler waveform seen in patients with portal
      hypertension and examined the associations of the waveform type with the
      diagnosis of Budd-Chiari syndrome and severity of the liver cirrhosis. METHODS:
      The Doppler pattern of right and left hepatic veins in 100 consecutive Japanese
      patients with portal hypertension and esophagogastric varices was classified into
      six types: I, triphasic waveform; II, biphasic waveform without reversed flow;
      III, decreased amplitude of phasic oscillations; IV, flat waveform with
      fluttering; V, completely flat waveform with fluttering; VI, no waveform. All
      patients underwent computed tomography and magnetic resonance imaging. Patients
      in whom hepatic vein waveform showed type IV, type V, or type VI, positively
      underwent hepatic venography and inferior vena cavography. RESULTS: Type I was
      seen in 31 of 100 patients, type II in 35, type III in 17, type IV in eight, type
      V in four, and type VI in five. Types I-IV waveform indicated no lesion in
      hepatic veins and inferior vena cava, type V indicated stenosis of hepatic veins
      or occlusion of inferior vena cava, and type VI, occlusion of hepatic veins. For
      one patient with type V hepatic veins, balloon angioplasty was done, and the
      waveform changed from type V to type II. Examining the relationship between
      hepatic vein waveform and the Child-Pugh score, liver function of type IV cases
      was worse than that of type I cases in 66 cirrhotic patients without
      hepatocellular carcinoma (p < 0.05). There was no clear relationship between
      hepatic vein waveform and portal venous perfusion, as based on Nordlinger's
      grade. CONCLUSIONS: Our classification of hepatic vein waveform in Doppler
      ultrasonography is useful in diagnosing Budd-Chiari syndrome, in judging the
      efficiency of treatment for hepatic vein lesions, and in assessing severe liver
      function in cirrhotic patients.

PMID- 8304298
TI  - Evaluation of patients who meet clinical criteria for irritable bowel syndrome.
AB  - OBJECTIVE: To determine which test would yield the most useful clinical data in
      evaluation of irritable bowel syndrome (IBS). METHODS: One hundred ninety-six
      patients who met the International Congress of Gastroenterology criteria for
      irritable bowel syndrome were prospectively evaluated with hematological,
      biochemical, and metabolic laboratory testing, as well as a structural evaluation
      of the colon. RESULTS: complete blood count, sedimentation rate (ESR), serum
      chemistries, thyroid profile, and urinalysis were normal or yielded no useful
      clinical information. Stool examinations for parasites were also normal.
      Structural evaluations (barium enema, x-ray, and flexible sigmoidoscopy or
      colonoscopy) revealed abnormalities, including colon cancer (1), polyps (9),
      colitis (1), melanosis coli (2), diverticulosis (17), and hemorrhoids (11). Forty
      eight subjects (25.8%) had lactose maldigestion confirmed by H2 breath lactose
      testing. Prior to formal testing, 25 (52%) of these subjects were unaware of the
      relationship between lactose-containing foods and their symptoms. CONCLUSIONS: 1)
      ESR, thyroid profiles, and parasite examinations had no diagnostic yield in this
      study and, without specific clinical indication from history and physical
      examination, should not be part of the "routine" IBS evaluation. 2) Lactose
      hydrogen breath testing is encouraged for patients with and without milk
      intolerance who present with IBS.

PMID- 8304299
TI  - Treatment of refractory ulcerative proctosigmoiditis with butyrate enemas.
AB  - BACKGROUND: It is well established that the colonic mucosa is highly dependent
      upon the luminal presentation of nutrients. This dependence is most marked in the
      distal colon. The major luminal nutrients are short chain fatty acids (SCFA) that
      are produced as a by-product of colonic fermentation of carbohydrates. Butyrate
      appears to be the SCFA that is most avidly metabolized by the colonic mucosa. It
      has been suggested that ulcerative colitis (UC) is, at least in part, related to
      an energy deficiency state of the colonic mucosa which may be secondary to
      impaired SCFA production, uptake, or utilization. OBJECTIVE: To determine if
      butyrate enemas are safe and effective in refractory distal UC. METHODS: Ten
      patients with distal UC, refractory to all other available forms of rectal
      therapy and to oral sulfasalazine or mesalamine (5-ASA), were treated with
      nightly butyrate enemas in an open-label study. Enemas consisted of 60 ml of 80
      mM sodium butyrate titrated to a pH of 7.0. Patients were assessed clinically and
      endoscopically at baseline and at 3- to 6-wk intervals, and a disease activity
      score from 0 to 12 was determined. Response to therapy was determined by changes
      in the activity score. RESULTS: Six of 10 patients responded to therapy. Four of
      these six had complete responses. The mean disease activity score of all 10
      patients fell from 8.0 +/- 2.4 (mean +/- SD) to 4.3 +/- 4.1 at the end of follow
      up. Response to therapy could not be predicted based on any of the baseline
      characteristics analyzed. CONCLUSIONS: In this open-label study, patients with
      distal UC who were refractory to all previous therapy had a 40% complete response
      rate and an overall 60% response rate. Controlled studies of this promising
      therapy are indicated.

PMID- 8304300
TI  - Intrahepatic arteriovenous shunting due to hepatocellular carcinoma and
      cirrhosis, and its change by transcatheter arterial embolization.
AB  - OBJECTIVES: To investigate intrahepatic arteriovenous shunt rate due to cirrhosis
      and hepatocellular carcinoma (HCC), complicated by cirrhosis, and its change
      after transcatheter arterial embolization. METHODS: The shunt rate was measured
      by hepatic artery infusion of labeled macroaggregated albumin. Counts were taken
      over the liver and both lungs for calculation of the shunt rate: cpm in lungs
      divided by (cpm in liver and lungs) x 100%. RESULTS: The intrahepatic
      arteriovenous shunt rate of cirrhosis ranged from 6.8% to 16.6% (12.6% +/- 3.4%,
      mean +/- SD). In HCC, it ranged from 7.2% to 27.1% (16.0% +/- 4.9%, mean +/- SD).
      The difference between the groups was statistically significant (p < 0.05). When
      the liver was more than 20% replaced by tumor, the intrahepatic arteriovenous
      shunt rate was higher than when less than 20% occupied (n = 6, 20.1% +/- 4.8% vs.
      n = 15, 14.4% +/- 4.0%; p < 0.05). Although the former was significantly
      different from liver cirrhosis, the latter was not significantly different from
      the shunt rate observed in liver cirrhosis without HCC. After transcatheter
      arterial embolization, excluding one patient who developed a visible hepatofugal
      arterioportal shunt, the mean change in shunt rate between the effective
      treatment group (n = 9, -2.1% +/- 2.8%, mean +/- SD) and the ineffective
      treatment group (n = 5, 3.0% +/- 3.3%, mean +/- SD) was statistically significant
      (p < 0.05). CONCLUSIONS: We found that intrahepatic arteriovenous shunt rate more
      sensitively detects intrahepatic arteriovenous shunting due to HCC than does
      angiography alone. Measuring intrahepatic arteriovenous stunt rate may provide
      useful information regarding response to treatment.

PMID- 8304301
TI  - Investigation of resected multinodular hepatocellular carcinoma: assessment of
      unicentric or multicentric genesis from histological and prognostic viewpoint.
AB  - OBJECTIVES: Multicentricity of hepatocellular carcinoma (HCC) is attracting a
      great deal of attention at present. However, few studies have focused on the
      prognostic comparison between unicentric and multicentric multinodular HCCs. The
      aim of this study is the reevaluation of histologic criteria of multicentric HCC
      and a prognostic comparison between the two groups mentioned above. METHODS:
      Forty-nine cases with intrahepatic multiple nodules of HCC, by gross examination,
      among 184 consecutive resected HCCs were examined clinicopathologically. These
      cases were divided into three groups: group A, cases suggestive of multicentric
      genesis; group B, unicentric cases; and group C, indeterminate cases.
      Histopathological characteristics and the cumulative survival rates were compared
      among these groups. RESULTS: Five cases were categorized as group A, 36 cases as
      group B, and eight cases as group C. Nodules in group A were smaller than 2 cm in
      diameter, situated discretely and well differentiated, and with neither vascular
      nor capsular invasion. Most of the nodules lacked a tumor capsule and had an
      irregular border. In the 36 cases of group B, all main tumors had vascular and/or
      capsular invasion. The cellularity index was almost the same in all groups. The
      cumulative survival rate of group A was better than that of group B or group C.
      CONCLUSIONS: Small multiple nodules of well-differentiated hepatocellular
      carcinoma without vascular and capsular invasion might be multicentric, and these
      early detections and operations could result in a fairly good prognosis, despite
      the multiple HCC nodules.

PMID- 8304302
TI  - The effect of percutaneous ethanol injection therapy on small solitary
      hepatocellular carcinoma is comparable to that of hepatectomy.
AB  - OBJECTIVES: Forty patients with solitary hepatocellular carcinoma (HCC) smaller
      than 20 mm in diameter were admitted to our hospitals from March 1986 to December
      1989. Of that 40 patients, 17 were treated with hepatectomy, 12 with percutaneous
      ethanol injection therapy, and 11 with the combination of percutaneous ethanol
      injection therapy and transcatheter arterial embolization. METHOD: Following up
      the patients after their first treatment for 2 months to 6 yr, as of April 30,
      1993, we evaluated the effects of hepatectomy, percutaneous ethanol injection
      therapy, and the combination of percutaneous ethanol injection therapy and
      transcatheter arterial embolization. RESULTS: Of the 23 patients who did not
      undergo surgery, eight died from recurrence of HCC and one died from ruptured
      varices. Of the 14 surviving patients, 10 experienced recurrences during the
      follow-up period. Of the 17 patients who underwent surgery, one died in hospital
      and four died from recurrence of carcinoma. Of the remaining 12 patients, nine
      experienced recurrences. The cumulative survival and recurrence rates were
      similar in operated and nonoperated patients. There was no significant difference
      in these rates in patients treated with versus without transcatheter arterial
      embolization. CONCLUSION: Our results showed that the efficacy of hepatectomy and
      the efficacy percutaneous ethanol injection therapy for small solitary HCC were
      similar. However, percutaneous ethanol injection therapy was safer and less
      expensive than hepatectomy.

PMID- 8304303
TI  - One-year follow-up of duodenal ulcers after 1-wk triple therapy for Helicobacter
      pylori.
AB  - OBJECTIVE: to study the ulcer recurrence rate of Helicobacter pylori-positive
      duodenal ulcers at 1 yr after eradication of the bacteria by triple therapy.
      METHOD: Patients with H. pylori-positive duodenal ulcers were randomized to
      receive either triple therapy for 1 wk plus omeprazole for 4 wk (Triple+OMP) (n =
      78), or omeprazole alone (OMP) for 4 wk (N = 77). Patients were followed up every
      3 months for symptom enquiry. At 1 yr, all asymptomatic patients were invited to
      attend for gastroscopy. RESULTS: At 8 wk, 16 patients in the OMP group and four
      in the Triple+OMP group had an ulcer. During the 1-yr period, 12 patients in the
      OMP group and no patient in the Triple+OMP group developed symptomatic ulcers. At
      follow-up endoscopy at 1 yr, another 10 ulcers were detected in the OMP group and
      two in the Triple+OMP group. Fifteen patients in the OMP group and 13 in the
      Triple+OMP group were lost to follow-up. In total, ulcers were detected in 39 of
      61 (64%) assessable patients in the OMP group, and in six of 65 (9%) assessable
      patients in the Triple+OMP group after 1 yr (chi 2 test: p < 0.001). Of the
      patients whose H. pylori were successfully eradicated by Triple+OMP at 8 wk, 90%
      remained H. pylori negative at 1 yr. CONCLUSION: Triple therapy for 1 wk
      eradicates H. pylori infection and significantly reduces duodenal ulcer relapses.

PMID- 8304304
TI  - Helicobacter pylori infection and development of gastric or duodenal ulcer in
      arthritic patients receiving chronic NSAID therapy. The Misoprostol Study Group.
AB  - OBJECTIVES: Helicobacter pylori infection and nonsteroidal anti-inflammatory drug
      use are both common causes of peptic ulcer. It remains unclear whether H.
      pylori/NSAID interactions occur, and if they do, with what result(s). METHODS: We
      prospectively evaluated development of gastric or duodenal ulcers in 181
      arthritics followed for up to 3 months while receiving an NSAID chronically and
      with no active anti-ulcer medications. H. pylori status was determined with a
      sensitive, specific ELISA for anti-H. pylori IgG. RESULTS: H. pylori infection
      was present in 51%; peptic ulcers developed in 24. H. pylori infection was
      present in only 36% of those who developed a duodenal ulcer. Stepwise logistic
      regression analysis indicated none of the variable factors of age, gender,
      alcohol consumption, type of arthritis, or H. pylori status were significantly
      associated with development of peptic ulceration. CONCLUSIONS: These data suggest
      that H. pylori does not confer increased risk of ulceration in arthritics
      receiving NSAIDs chronically.

PMID- 8304305
TI  - Establishment of a small animal model for human Helicobacter pylori infection
      using germ-free mouse.
AB  - OBJECTIVE: To understand why oral inoculation of Helicobacter pylori resulted in
      continuous colonization of the stomach in germ-free athymic mice, but only
      temporary colonization in mice that were not germ-free. METHODS: We inoculated
      germ-free and "not-germ-free" euthymic mice with H. pylori and studied the
      resulting colonization of the stomach, comparing it against the germ-free athymic
      mouse model. In addition, we investigated Lactobacillus in the above-described
      three mouse groups. RESULTS: H. pylori were detected in all germ-free athymic
      mice and all germ-free euthymic mice continuously. However, in all euthymic mice
      that were not germ-free, H. pylori was detected only temporarily after
      inoculation. Lactobacilli were detected only in the not-germ-free mouse group.
      The number of H. pylori in the germ-free euthymic mice was significantly lower
      than in the germ-free athymic mice during the period of this study after
      inoculation. CONCLUSIONS: We therefore suggest that the growth of H. pylori may
      be suppressed by the immunological system and eradicated by Lactobacilli
      previously inhabiting the stomach.

PMID- 8304306
TI  - Comparison of the effects of single morning and single bedtime doses of
      famotidine on intragastric acidity in patients with gastric ulcer.
AB  - The effects of single morning and single bedtime doses of famotidine on
      intragastric acidity were studied by 24-h intragastric pH monitoring in 16
      patients with gastric ulcer. The patients were randomly allocated to the
      following regimen: one group (n = 8) received 40 mg famotidine at 8:30 AM and
      another group (n = 8) received the same dose at 10 PM. The morning group showed
      significant inhibition of gastric acidity during the 24-h and daytime
      measurements, compared to those of the bedtime group (p < 0.05 in 24 h, p < 0.01
      in daytime). Conversely, the bedtime group showed a significant inhibition of
      gastric acidity during the nocturnal period compared to the morning group (p <
      0.01). These results indicate that the relative importance of suppression of
      gastric acidity on the gastric ulcer healing process should be evaluated in a
      clinical trial.

PMID- 8304307
TI  - Flow cytometry and in vitro tritiated thymidine labeling in normal rectal mucosa
      of patients at high risk of colorectal cancer.
AB  - OBJECTIVES: To compare two different methods to evaluate rectal epithelial cell
      proliferation as a biomarker of risk of developing colon cancer. METHODS: Samples
      of normal rectal mucosa from 26 patients at increased risk for colorectal cancer
      (22 patients with adenoma, three with adenocarcinoma of the large bowel, and one
      with longstanding ulcerative colitis) were examined by means of in vitro labeling
      with tritiated thymidine and flow cytometry. RESULTS: We found a significant
      correlation between thymidine-labeling index and the percentage of cells in S
      phase, measured by flow cytometry both in formalin-fixed, paraffin-embedded
      specimens and in frozen specimens (respectively, r = 0.7647, p < 0.001, and r =
      0.4503, p < 0.01). However, using flow cytometry, the percentage of cells in S
      phase was significantly higher than the thymidine-labeling index in both fixed
      embedded and frozen specimens (p < 0.01). Proliferative parameters were not
      higher in patients with colon carcinoma, and were not related to the degree of
      dysplasia, the number of adenomas, or familial occurrence of colorectal cancer.
      Two specimens taken from normal rectal mucosa of two patients with adenomas
      showed aneuploidy. No aneuploidy was found in normal rectal specimens of patients
      with adenocarcinoma. CONCLUSIONS: These results show that the calculation of
      cells in S-phase with in vitro tritiated thymidine labeling or by flow cytometry
      produces different results. However, the significant correlation between
      corresponding parameters obtained with these techniques support the use of either
      method as "intermediate biomarkers" of colorectal cancer risk and prognosis.

PMID- 8304308
TI  - Gallbladder emptying to endogenous and exogenous stimulation in chronic
      pancreatitis patients.
AB  - OBJECTIVES: The present study was designed to analyze the underlying mechanism of
      gallbladder motor disturbance in chronic pancreatitis patients. METHODS:
      Gallbladder emptying to endogenous (oral test meal, Daiyan 13 g) and exogenous
      stimulation (iv cerulein, 30 ng/kg for 5 min) was examined by real-time
      ultrasonography in 12 patients with chronic pancreatitis and 10 normal subjects
      (controls). Plasma cholecystokinin levels during the endogenous stimulation were
      measured by bioassay. RESULTS: In chronic pancreatitis patients compared with
      controls, the fasting gallbladder volume was significantly increased (29.5 +/-
      2.2 vs. 21.5 +/- 2.8 ml), whereas the gallbladder emptying (percent change of the
      basal volume) to oral test meal was significantly decreased. Neither
      cholecystokinin secretion induced by the test meal, nor the gallbladder emptying
      response to intravenous cerulein, differed significantly between the two groups.
      However, when chronic pancreatitis patients were divided according to
      pathogenesis, it became clear that gallbladder emptying to intravenous cerulein
      was significantly greater in patients with alcoholic chronic pancreatitis than in
      patients with idiopathic pancreatitis. CONCLUSIONS: Gallbladder emptying during
      the intestinal phase is generally reduced in patients with chronic pancreatitis,
      but gallbladder responsiveness to exogenous stimulation might be heterogeneous
      according to the pathogenesis.

PMID- 8304309
TI  - Sulglycotide effect on the proteolytic and lipolytic activities of Helicobacter
      pylori toward gastric mucus.
AB  - OBJECTIVES: Infection with Helicobacter pylori is now recognized as a major
      factor in the etiology of gastric disease, and among the detrimental effects this
      bacterium exerts on the mucosal integrity is the elaboration of extracellular
      protease and lipase enzymes capable of mucus protein and lipids degradation. We
      present here evidence that the activities of these enzymes are inhibited by an
      gastroprotective agent, sulglycotide. METHODS: The grown colonies of bacterium
      were washed with saline, filtered through sterilization filter, and the filtrate
      used as the enzyme source. RESULTS: In the absence of sulglycotide, the H. pylori
      protease caused extensive degradation of human gastric mucus, while free fatty
      acids, glycerol monooleate and lysophosphatidylcholine were produced by the
      action of H. pylori lipase and phospholipase A enzymes. Introduction of
      sulglycotide to the incubation systems led to the reduction in the rate of mucus
      protein and lipid degradation. The rate of proteolysis inhibition was
      proportional to sulglycotide concentration up to 45 micrograms/ml, at which point
      a 43% reduction in mucus degradation was attained, whereas the maximum inhibition
      of lipase (39%) and phospholipase A (98%) activities occurred at a sulglycotide
      concentration of 100 micrograms/ml. CONCLUSIONS: This study indicates that
      sulglycotide is capable of counteracting the mucolytic activity of H. pylori, and
      thus may be of value in the therapy of H. pylori-associated gastric diseases.

PMID- 8304310
TI  - Impairment of salivary epidermal growth factor secretory response to esophageal
      mechanical and chemical stimulation in patients with reflux esophagitis.
AB  - OBJECTIVES: It has been demonstrated recently that salivary epidermal growth
      factor (sEGF) output in healthy individuals is strongly and significantly
      influenced by esophageal intraluminal mechanical and chemical stimuli. Therefore,
      we have studied the impact of intraesophageal mechanical and chemical stressors
      on the rate of secretion of sEGF in 14 patients with reflux esophagitis (RE), and
      compared these results with corresponding parameters measured in 14 sex- and age
      matched controls. METHODS: EGF was assessed in saliva collected during basal
      conditions, chewing of parafilm, placement of esophageal tubing, inflation of
      intraesophageal balloons, and perfusion with NaCl, HCl, and HCl/pepsin solutions.
      The concentration of sEGF was measured with an RIA kit from Amersham (Arlington
      Heights, IL). RESULTS: The concentrations of sEGF were (mean +/- SEM) 2.50 +/-
      0.32 ng/ml and 2.00 +/- 0.37 ng/ml in basal saliva and during stimulation by
      chewing the parafilm, respectively. Basal sEGF value appeared to be significantly
      higher than in controls (2.50 +/- 0.32 vs. 1.90 +/- 0.22 ng/ml, p < 0.05, in one
      tailed t test). Placement of intraesophageal tubing resulted in a significant
      decline of sEGF concentration, compared with parafilm-stimulated conditions (1.25
      +/- 0.12 vs. 2.00 +/- 0.37 ng/ml, p < 0.0001) and corresponding tubing-stimulated
      sEGF value in controls (1.25 +/- 0.12 vs. 1.52 +/- 0.16 ng/ml, p < 0.05). sEGF
      concentrations after inflation of intraesophageal balloons and subsequent
      perfusion with initial saline, HCl, HCl/pepsin, and ending saline were also
      highly significantly lower (1.05 +/- 0.18 ng/ml, p < 0.001; 1.10 +/- 0.20 ng/ml,
      p < 0.001; 1.10 +/- 0.18 ng/ml, p < 0.001; 1.10 +/- 0.19 ng/ml, p < 0.001; and
      1.05 +/- 0.18 ng/ml, p < 0.001, respectively) than sEGF concentration recorded
      during stimulation with parafilm. Concentrations of sEGF during esophageal
      perfusion with HCl, HCl/pepsin, and ending saline were also significantly lower
      than corresponding values in controls (1.10 +/- 0.18 vs. 1.49 +/- 0.11 ng/ml, p <
      0.05; 1.10 +/- 0.19 vs. 1.59 +/- 0.11 ng/ml, p < 0.05; and 1.05 +/- 0.18 vs. 1.65
      +/- 0.13 ng/ml, p < 0.01, respectively). The rate of sEGF output, which was 1.30
      +/- 0.24 ng/min during basal conditions, increased significantly during
      stimulation with parafilm (2.30 +/- 0.38 ng/min, p < 0.05). Both basal and
      parafilm-stimulated sEGF outputs were somewhat higher, although nonsignificantly,
      than corresponding values recorded in healthy individuals. Mechanical and
      chemical stimulation (initial NaCl, HCl, and ending NaCl) failed to evoke a
      significant increase in sEGF output over the value observed during parafilm
      stimulation in patients with RE, although such a significant increase was clearly
      demonstrated in healthy individuals. Therefore, sEGF output in patients with RE
      remained significantly lower than corresponding values recorded in controls
      during an entire mechanical stimulation (2.65 +/- 0.35 vs. 4.60 +/- 0.85 ng/min,
      p < 0.001, after placement of intraesophageal tubing and 2.80 +/- 0.54 vs. 5.15
      +/- 0.70 ng/min, p < 0.001, after inflation of balloons). sEGF output in patients
      with RE remained also significantly lower than adequate control values during
      chemical stimulation (3.65 +/- 0.64 vs. 5.20 +/- 0.60 ng/min, p < 0.05, during
      perfusion with initial saline; 3.70 +/- 0.70 vs. 5.20 +/- 0.60 ng/min, p < 0.05,
      during perfusion with HCl; 3.70 +/- 0.52 vs. 5.55 +/- 0.72 ng/min, p < 0.01,
      during perfusion with HCl/pepsin, and 3.30 +/- 0.56 vs. 5.80 +/- 0.86 ng/min, p <
      0.001, during ending saline). CONCLUSION: Impairment in sEGF secretion during
      mechanical and chemical intraesophageal stimulation, mimicking the natural
      scenario occurring during gastroesophageal reflux, may facilitate the development
      of esophageal mucosal pathology and delay the healing of already developed
      mucosal injury.

PMID- 8304311
TI  - Squamous cell papilloma of the esophagus: a clinicopathologic and follow-up study
      of 25 cases.
AB  - OBJECTIVES: The aim of this study was to correlate clinical and pathologic
      features of squamous cell papillomas of the human esophagus and investigate their
      pathogenesis and malignant potential. METHODS: Clinical and pathologic data on 25
      patients were studied. RESULTS: All patients in whom the race was known were
      white, and the majority of lesions occurred in the distal esophagus. There were
      multiple lesions in five cases. Many cases showed endoscopic evidence of hiatus
      hernia, gastroesophageal reflux, or esophagitis. No examples of Barrett esophagus
      were found. No esophageal malignancies occurred, and no dysplasia was seen
      histologically. Evidence of recurrence was found in only two patients, but
      several synchronous or metachronous carcinomas of the oro-respiratory tract
      occurred. CONCLUSIONS: Although our findings do not exclude a viral etiology,
      they suggest a role for mucosal injury and regeneration in the pathogenesis of
      these lesions. The association with other malignancies may be significant.

PMID- 8304312
TI  - Radiological study of idiopathic Budd-Chiari syndrome complicated by
      hepatocellular carcinoma. A report of four cases.
AB  - During an 11-yr period (1979-1989), we have experienced five patients with
      idiopathic Budd-Chiari syndrome (BCS), four (80%) of whom had associated
      hepatocellular carcinoma (HCC). In contrast, the incidence of BCS complicated by
      HCC was 0.7% of a total of 556 patients who underwent surgery for HCC or were
      autopsied. Hepatitis B virus-related antigen or antibody was positive in one
      patient each. Four of our five patients were asymptomatic and were initially
      diagnosed by ultrasonography (n = 3) or computed tomography (n = 1). The hepatic
      parenchyma histopathological findings were cirrhosis and fibrosis in one each.
      Infection of hepatitis B virus rather than BCS was speculated as a causative
      factor for HCC in two patients. Membranous obstruction with spotty calcification,
      intrahepatic bizarre communicating vessels, and the dilated anterior longitudinal
      veins in  spinal canal were recognized in three patients. Three patients had two
      HCCs which were similar in size and arose from the right and left hepatic lobe,
      separately, suggesting multicentricity of HCC. Both percutaneous transluminal
      angioplasty with Gruntzig balloon catheters for the obstruction of the inferior
      vena cava and hepatic arterial embolization for HCC(s) were performed in three
      patients. These patients survived 29.3 months on average after the diagnosis of
      BCS complicated by HCC(s). The opened IVC was confirmed to be patent on an
      average of 26.3 months after the first angioplasty.

PMID- 8304313
TI  - Colon adenocarcinoma in HIV infection: a case report and review.
AB  - Gastrointestinal adenocarcinoma is a disease seen uncommonly in HIV-infected
      patients. The present case is that of a 25-yr-old black male who was HIV positive
      and developed right-sided colon adenocarcinoma. This case is an example of the
      growing number of adenocarcinomas of the gastrointestinal tract being reported in
      HIV patients. Cases of gastric, pancreatic, and colonic adenocarcinoma in HIV
      patients are reviewed herein. It seems possible that HIV may play an etiologic
      role in the increased chance of developing gastrointestinal adenocarcinoma.

PMID- 8304314
TI  - Clinical evaluation of four cases of acute viral hepatitis complicated by pure
      red cell aplasia.
AB  - Four patients with acute viral hepatitis complicated by pure red cell aplasia
      were clinically evaluated. Two patients with hepatitis type A, one with hepatitis
      type B, and one with posttransfusion non-A non-B hepatitis had pure red cell
      aplasia. Only the patient with posttransfusion hepatitis was female, and the mean
      age of the four patients was 37.8 yr (31-51 yr.) The mean interval from the onset
      of hepatitis to the appearance of pure red cell aplasia was 30.5 days (27-37
      days), and the development of hematopoietic disorders coincided with decreases in
      transaminase levels. Laboratory findings included peak serum glutamate pyruvate
      transaminase levels of 1305-3160 KU and decreases in the prothrombin time to
      about 50% in the two patients with hepatitis type A. Pure red cell aplasia was
      successfully treated by prednisolone or transfusion in all patients.

PMID- 8304315
TI  - Endoscopic ultrasound-guided fine needle aspiration of pancreatic carcinoma.
AB  - Endoscopic ultrasound (EUS) is reported to be the single best modality for
      visualizing small pancreatic carcinomas. Whereas tissue diagnosis by fine needle
      aspiration (FNA) can be performed with computed tomography (CT) or transabdominal
      ultrasound guidance, the diagnostic accuracy is limited by the ability of these
      modalities to visualize the lesion. Real time EUS-guided fine needle aspiration
      has recently been reported as a new diagnostic modality. The application of EUS
      guided FNA in the diagnosis of small pancreatic carcinoma has not been reported.
      We present a case in which transduodenal EUS-guided FNA was successful in
      establishing a definitive tissue diagnosis of pancreatic carcinoma in a 1.6-cm
      lesion in the head of the pancreas. This case along with a review of the
      literature highlights the great potential of this new modality in the diagnosis
      of pancreatic carcinoma.

PMID- 8304316
TI  - Glomus tumor of the stomach: endoscopic ultrasonographic findings.

PMID- 8304317
TI  - Leishmania esophagitis in an AIDS patient: an unusual form of visceral
      leishmaniasis.
AB  - Esophageal disease is a common cause of morbidity in patients infected by human
      immunodeficiency virus (HIV). Although gastrointestinal involvement of
      leishmaniasis has been previously reported, we believed that we describe the
      first case of leishmania esophagitis. Clinical data and the endoscopic and
      histologic hallmarks are described.

PMID- 8304318
TI  - The endosonographic appearance of a Dieulafoy's lesion.

PMID- 8304319
TI  - Strangulated obturator hernia: a rare cause of small bowel obstruction.

PMID- 8304320
TI  - Severe cholestasis associated with ticlopidine.

PMID- 8304321
TI  - Colon trek: the next generation?

PMID- 8304322
TI  - Banding together to treat esophageal varices.

PMID- 8304323
TI  - Re: Current treatment modalities for symptomatic gallstones.

PMID- 8304324
TI  - Gastric carcinoid associated with ranitidine and renal failure.

PMID- 8304325
TI  - Barrett's esophagus: an unlikely diagnosis in infants and young children.

PMID- 8304326
TI  - Ketorolac-associated upper gastrointestinal hemorrhage.

PMID- 8304327
TI  - Esophageal metastases from breast cancer detected by hematemesis.

PMID- 8304328
TI  - Severe pancytopenia after cimetidine therapy.

PMID- 8304329
TI  - Aeromonas sobria spontaneous bacterial peritonitis and bacteremia.

PMID- 8304330
TI  - Bicycle racing, Raynaud's phenomenon, and gastrointestinal bleeding.

PMID- 8304331
TI  - Mallory Weiss tears due to colonoscopy preps.

PMID- 8304332
TI  - Sex ratio of Helicobacter pylori infection in childhood.

PMID- 8304333
TI  - An interdisciplinary approach to identifying a bronchoesophageal fistula.

PMID- 8304334
TI  - Aspiration of small bowel contents.

PMID- 8304335
TI  - Of mice and men: heritable skeletal disorders.

PMID- 8304336
TI  - Amino acid substitutions of conserved residues in the carboxyl-terminal domain of
      the alpha 1(X) chain of type X collagen occur in two unrelated families with
      metaphyseal chondrodysplasia type Schmid.
AB  - Type X collagen is a homotrimeric, short-chain, nonfibrillar extracellular-matrix
      component that is specifically and transiently synthesized by hypertrophic
      chondrocytes at the sites of endochondral ossification. The precise function of
      type X collagen is not known, but its specific pattern of expression suggests
      that mutations within the encoding gene (COL10A1) that alter the structure or
      synthesis of the protein may cause heritable forms of chondrodysplasia. We used
      the PCR and the SSCP techniques to analyze the coding and upstream promoter
      regions of the COL10A1 gene in a number of individuals with forms of
      chondrodysplasia. Using this approach, we identified two individuals with
      metaphyseal chondrodysplasia type Schmid (MCDS) with SSCP changes in the region
      of the gene encoding the carboxyl-terminal domain. Sequence analysis demonstrated
      that the individuals were heterozygous for two unique single-base-pair
      transitions that led to the substitution of the highly conserved amino acid
      residue tyrosine at position 598 by aspartic acid in one person and of leucine at
      position 614 by proline in the other. The substitution at residue 598 segregated
      with the phenotype in a family of eight (five affected and three unaffected)
      related persons. The substitution at residue 614 occurred in a sporadically
      affected individual but not in her unaffected mother and brother. Additional
      members of this family were not available for further study. These results
      suggest that certain amino acid substitutions within the carboxyl-terminal domain
      of the chains of the type X collagen molecule cause MCDS. These amino acid
      substitutions are likely to alter either chain recognition or assembly of the
      type X collagen molecule, thereby depleting the amount of normal type X collagen
      deposited in the extracellular matrix, with consequent aberrations in bone growth
      and development.

PMID- 8304337
TI  - Clinical heterogeneity within xeroderma pigmentosum associated with mutations in
      the DNA repair and transcription gene ERCC3.
AB  - The human DNA excision repair gene ERCC3 specifically corrects the nucleotide
      excision repair (NER) defect of xeroderma pigmentosum (XP) complementation group
      B. In addition to its function in NER, the ERCC3 DNA helicase was recently
      identified as one of the components of the human BTF2/TFIIH transcription factor
      complex, which is required for initiation of transcription of class II genes. To
      date, a single patient (XP11BE) has been assigned to this XP group B (XP-B), with
      ther remarkable conjunction of two autosomal recessive DNA repair deficiency
      disorders: XP and Cockayne syndrome (CS). The intriguing involvement of the ERCC3
      protein in the vital process of transcription may provide an explanation for the
      rarity, severity, and wide spectrum of clinical features in this complementation
      group. Here we report the identification of two new XP-B patients: XPCS1BA and
      XPCS2BA (siblings), by microneedle injection of the cloned ERCC3 repair gene as
      well as by cell hybridization. Molecular analysis of the ERCC3 gene in both
      patients revealed a single base substitution causing a missense mutation in a
      region that is completely conserved in yeast, Drosophila, mouse, and human ERCC3.
      As in patient XP11BE, the expression of only one allele (paternal) is detected.
      The mutation causes a virtually complete inactivation of the NER function of the
      protein. Despite this severe NER defect, both patients display a late onset of
      neurologic impairment, mild cutaneous symptoms, and a striking absence of skin
      tumors even at an age of > 40 years. Analysis of the frequency of hprt- mutant T
      lymphocytes in blood samples suggests a relatively low in vivo mutation frequency
      in these patients. Factors in addition to NER deficiency may be required for the
      development of cutaneous tumors.

PMID- 8304338
TI  - The rates and patterns of deletions in the human factor IX gene.
AB  - Deletions are commonly observed in genes with either segments of highly
      homologous sequences or excessive gene length. However, in the factor IX gene and
      in most genes, deletions (of > or = 21 bp) are uncommon. We have analyzed DNA
      from 290 families with hemophilia B (203 independent mutations) and have found 12
      deletions > 20 bp. Eleven of these are > 2 kb (range > 3-163 kb), and one is 1.1
      kb. The junctions of the four deletions that are completely contained within the
      factor IX gene have been determined. A novel mutation occurred in patient HB128:
      the data suggest that a 26.8-kb deletion occurred between two segments of
      alternating purines and pyrimidines and that a 2.3-kb sense strand segment
      derived from the deleted region was inserted. For our sample of 203 independent
      mutations, we estimate the "baseline" rates of deletional mutation per base pair
      per generation as a function of size. The rate for large (> 2 kb) deletions is
      exceedingly low. For every mutational event in which a given base is at the
      junction of a large deletion, there are an estimated 58 microdeletions (< 20 bp)
      and 985 single-base substitutions at that base. Analysis of the nine reported
      deletion junctions in the factor IX gene literature reveals that (i) five are
      associated with inversions, orphan sequences, or sense strand insertions; (ii)
      four are simple deletions that display an excess of short direct repeats at their
      junctions; (iii) there is no dramatic clustering of junctions within the gene;
      and (iv) with the exception of alternating purines and pyrimidines, deletion
      junctions are not preferentially associated with repetitive DNA.

PMID- 8304339
TI  - Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy.
AB  - Genetic linkage studies were conducted in four multigenerational families with X
      linked Charcot-Marie-Tooth disease (CMTX), using 12 highly polymorphic short
      tandem-repeat markers for the pericentromeric region of the X chromosome.
      Pairwise linkage analysis with individual markers confirmed tight linkage of CMTX
      to the pericentromeric region in each family. Multipoint analyses strongly
      support the order DXS337-CMTX-DXS441-(DXS56,PGK1).

PMID- 8304340
TI  - Genetic heterogeneity in X-linked hydrocephalus: linkage to markers within
      Xq27.3.
AB  - X-linked hydrocephalus is a well-defined disorder which accounts for > or = 7% of
      hydrocephalus in males. Pathologically, the condition is characterized by
      stenosis or obliteration of the aqueduct of Sylvius. Previous genetic linkage
      studies have suggested the likelihood of genetic homogeneity for this condition,
      with close linkage to the DXS52 and F8C markers in Xq28. We have investigated a
      family with typical X-linked aqueductal stenosis, in which no linkage to these
      markers was present. In this family, close linkage was established to the DXS548
      and FRAXA loci in Xq27.3. Our findings demonstrate that X-linked aqueductal
      stenosis may result from mutations at two different loci on the X chromosome.
      Caution is indicated in using linkage for the prenatal diagnosis of X-linked
      hydrocephalus.

PMID- 8304341
TI  - Isolation of novel non-HLA gene fragments from the hemochromatosis region
      (6p21.3) by cDNA hybridization selection.
AB  - It has previously been shown that cDNA hybridization selection can identify and
      recover novel genes from large cloned genomic DNA such as cosmids or YACs. In an
      effort to identify candidate genes for hemochromatosis, this technique was
      applied to a 320-kb YAC containing the HLA-A gene. A short fragment cDNA library
      derived from human duodenum was selected with the YAC DNA. Ten novel gene
      fragments were isolated, characterized, and localized on the physical map of the
      YAC.

PMID- 8304342
TI  - Anonymous marker loci within 400 kb of HLA-A generate haplotypes in linkage
      disequilibrium with the hemochromatosis gene (HFE)
AB  - The hemochromatosis gene (HFE) maps to 6p21.3 and is less than 1 cM from the HLA
      class I genes; however, the precise physical location of the gene has remained
      elusive and controversial. The unambiguous identification of a crossover event
      within hemochromatosis families is very difficult; it is particularly hampered by
      the variability of the phenotypic expression as well as by the sex- and age
      related penetrance of the disease. For these practical considerations,
      traditional linkage analysis could prove of limited value in further refining the
      extrapolated physical position of HFE. We therefore embarked upon a linkage
      disequilibrium analysis of HFE and normal chromosomes from the Brittany
      population. In the present report, 66 hemochromatosis families yielding 151
      hemochromatosis chromosomes and 182 normal chromosomes were RFLP-typed with a
      battery of probes, including two newly derived polymorphic markers from the 6.7
      and HLA-F loci located 150 and 250 kb telomeric to HLA-A, respectively. The
      results suggest a strong peak of existing linkage disequilibrium focused within
      the i82-to-6.7 interval (approximately 250 kb). The zone of linkage
      disequilibrium is flanked by the i97 locus, positioned 30 kb proximal to i82, and
      the HLA-F gene, found 250 kb distal to HLA-A, markers of which display no
      significant association with HFE. These data support the possibility that HFE
      resides within the 400-kb expanse of DNA between i97 and HLA-F. Alternatively,
      the very tight association of HLA-A3 and allele 1 of the 6.7 locus, both of which
      are comprised by the major ancestral or founder HFE haplotype in Brittany,
      supports the possibility that the disease gene may reside immediately telomeric
      to the 6.7 locus within the linkage-disequilibrium zone. Additionally,
      hemochromatosis haplotypes possessing HLA-A11 and the low-frequency HLA-F
      polymorphism (allele 2) are supportive of a separate founder chromosome
      containing a second, independently arising mutant allele. Overall, the
      establishment of a likely "hemochromatosis critical region" centromeric boundary
      and the identification of a linkage-disequilibrium zone both significantly
      contribute to a reduction in the amount of DNA required to be searched for novel
      coding sequences constituting the HFE defect.

PMID- 8304343
TI  - The genetics of retinoblastoma, revisited.
AB  - Our epidemiological and genetic analyses of sporadic and familial retinoblastoma
      indicate that an X-chromosome-linked gene is involved in the genesis of a
      significant fraction of new bilateral cases of the disease. The activity of this
      gene results in sex-ratio distortion in favor of males among patients with
      bilateral sporadic disease. Among the offspring of these males, both sex-ratio
      distortion in favor of males and transmission-ratio distortion in favor of
      affecteds are observed. We propose that these phenomena are due to the inability
      of these males to erase the genome imprint established on the half of the genome
      inherited from their mothers.

PMID- 8304344
TI  - Concordance between parental origin of chromosome 13q loss and chromosome 6p
      duplication in sporadic retinoblastoma.
AB  - Two hypotheses are capable of explaining nonrandom loss of one parent's alleles
      at tumor suppressor loci in sporadic cases of several pediatric cancers,
      including retinoblastoma--namely, preferential germ-line mutation or chromosome
      imprinting. We have examined 74 cases of sporadic retinoblastoma for tumors in
      which at least two genetic events--loss of heterozygosity for chromosome 13q
      markers and formation of an isochromosome 6p--have occurred. Sixteen cases were
      found to contain both events. In 13 of 16 such tumors, the chromosomes 13q that
      were lost and chromosomes 6p that were duplicated are derived from the same
      parent. These data may be explained within the framework of the genome imprinting
      model but are not predicted by preferential germ-line mutation.

PMID- 8304345
TI  - Uniparental disomy occurs infrequently in Wilms tumor patients.
AB  - Wilms tumors commonly exhibit loss of heterozygosity for polymorphic DNA markers
      located on the short arm of chromosome 11 at band p15. In some instances, the
      deleted region does not include 11p13, the location of the WT1 gene, suggesting
      the existence of a second Wilms tumor gene on 11p. Both the exclusive loss of the
      maternally derived allele in Wilms tumors and the recent description of
      constitutional paternal isodisomy for this region in patients with either the
      Beckwith-Wiedemann syndrome (BWS) or isolated hemihypertrophy have suggested that
      this second locus is subject to sex-specific genomic imprinting. Given that one
      of these isodisomic patients had minimal congenital anomalies (hemihypertrophy),
      we hypothesized that a proportion of Wilms tumors which had not lost
      heterozygosity for 11p markers (about 60% of all cases) might have arisen
      consequent to 11p paternal heterodisomy and that patients constitutionally
      homozygous at 11p15 might harbor paternal isodisomy. We have analyzed 40 Wilms
      tumor cases to determine the parental origin of the child's 11p15 alleles.
      Paternal heterodisomy could be excluded in all 28 unilateral and 8/9 bilateral
      potential candidates. It is intriguing that somatic mosaicism for 11p paternal
      isodisomy was detected in one child with bilateral Wilms tumor and macroglossia.
      Isodisomy could only be excluded in one of the three possible cases. Thus, 11p
      paternal hetero- and isodisomy appear to be uncommon causes of non-anomaly
      associated Wilms tumors but may be more frequent in Wilms tumor patients with BWS
      associated anomalies.

PMID- 8304346
TI  - A somatic origin of homologous Robertsonian translocations and isochromosomes.
AB  - One t(14q14q), three t(15q15q), two t(21q21q), and two t(22q22q) nonmosaic,
      apparently balanced, de novo Robertsonian translocation cases were investigated
      with polymorphic markers to establish the origin of the translocated chromosomes.
      Four cases had results indicative of an isochromosome: one t(14q14q) case with
      mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14,
      one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically
      normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal
      t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity
      throughout the involved chromosome, which is supportive of a postmeiotic origin.
      In the remaining four cases, maternal and paternal inheritance of the involved
      chromosome was found, which unambiguously implies a somatic origin. One t(15q15q)
      female had a child with a ring chromosome 15, which was also of probable
      postmeiotic origin as recombination between grandparental haplotypes had occurred
      prior to ring formation. UPD might be expected to result from de novo
      Robertsonian translocations of meiotic origin; however, all de novo homologous
      translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22
      have been isochromosomes. These data provide the first direct evidence that
      nonmosaic Robertsonian translocations, as well as isochromosomes, are commonly
      the result of a mitotic exchange.

PMID- 8304347
TI  - mtDNA and Y-chromosome polymorphisms in four Native American populations from
      southern Mexico.
AB  - mtDNA sequence variation was examined in 60 Native Americans (Mixtecs from the
      Alta, Mixtecs from the Baja, Valley Zapotecs, and Highland Mixe) from southern
      Mexico by PCR amplification and high-resolution restriction endonuclease
      analysis. Four groups of mtDNA haplotypes (haplogroups A, B, C, and D)
      characterize Amerind populations, but only three (haplogroups A, B, and C) were
      observed in these Mexican populations. The comparison of their mtDNA variation
      with that observed in other populations from Mexico and Central America permits a
      clear distinction among the different Middle American tribes and raises questions
      about some of their linguistic affiliations. The males of these population
      samples were also analyzed for Y-chromosome RFLPs with the probes 49a, 49f, and
      12f2. This analysis suggests that certain Y-chromosome haplotypes were brought
      from Asia during the colonization of the Americas, and a differential gene flow
      was introduced into Native American populations from European males and females.

PMID- 8304348
TI  - The Y Alu polymorphism in southern African populations and its relationship to
      other Y-specific polymorphisms.
AB  - Y-linked polymorphisms were studied in a number of African populations. The
      frequency of the alleles of a Y-specific Alu insertion polymorphism, termed the
      "Y Alu polymorphism," was determined in 889 individuals from 23 different African
      population groups. A trend in frequency was observed, with the insert largely
      absent in Caucasoid populations, at intermediate frequency in the Khoisan, and at
      high frequency in Negroids. The insert predates diversification of Homo sapiens,
      since it occurs in all groups. The Alu insertion is believed to result from a
      unique mutation event, and comparisons between this and several other Y-linked
      polymorphisms were carried out in an attempt to validate their usefulness in
      population and evolutionary studies. The p21A1/TaqI and pDP31/EcoRI polymorphisms
      and 49a/TaqI alleles were all shown to have arisen on more than one occasion, and
      evidence exists for a preraciation crossover event between the Y-linked
      pseudoautosomal XY275 locus and the Y chromosome pseudoautosomal boundary.

PMID- 8304349
TI  - PCR/oligonucleotide probe typing of HLA class II alleles in a Filipino population
      reveals an unusual distribution of HLA haplotypes.
AB  - We have analyzed the distribution of HLA class II alleles and haplotypes in a
      Filipino population by PCR amplification of the DRB1, DQB1, and DPB1 second-exon
      sequences from buccal swabs obtained from 124 family members and 53 unrelated
      individuals. The amplified DNA was typed by using nonradioactive sequence
      specific oligonucleotide probes. Twenty-two different DRB1 alleles, including the
      novel Filipino *1105, and 46 different DRB1/DQB1 haplotypes, including the
      unusual DRB1*0405-DQB1*0503, were identified. An unusually high frequency (f =
      .383) of DPB1*0101, a rare allele in other Asian populations, was also observed.
      In addition, an unusual distribution of DRB1 alleles and haplotypes was seen in
      this population, with DR2 (f = .415) and DRB1*1502-DQB1*0502 (f = .233) present
      at high frequencies. This distribution of DRB1 alleles differs from the typical
      HLA population distribution, in which the allele frequencies are more evenly
      balanced. The distribution of HLA class II alleles and haplotypes in this
      Filipino population is different from that of other Asian and Pacific groups: of
      those populations studied to date; the Indonesian population is the most similar.
      DRB1*1502-DQB1*0502 was in strong linkage disequilibrium (D' = .41) with
      DPB1*0101 (f = .126, for the extended haplotype), which is consistent with
      selection for this DR, DQ, DP haplotype being responsible for the high frequency
      of these three class II alleles in this population.

PMID- 8304350
TI  - Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not
      triglyceride concentrations.
AB  - To quantify the effect of the apolipoprotein (apo) E polymorphism on the
      magnitude of postprandial lipemia, we have defined its role in determining the
      response to a single high-fat meal in a large sample of (N = 474) individuals
      taking part in the biethnic Atherosclerosis Risk in Communities Study. The
      profile of postprandial response in plasma was monitored over 8 h by
      triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B
      100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was
      determined by DNA amplification and digestion. The frequency of the apo E alleles
      and their effects on fasting lipid levels in this sample were similar to those
      reported elsewhere. Postprandial plasma retinyl palmitate response to a high-fat
      meal with vitamin A was significantly different among apo E genotypes, with
      delayed clearance in individuals with an epsilon 2 allele, compared with epsilon
      3/3 and epsilon 3/4 individuals. In the sample of 397 Caucasians, average retinyl
      palmitate response was 1,489 micrograms/dl in epsilon 2/3 individuals, compared
      with 1,037 micrograms/dl in epsilon 3/3 individuals and 1,108 micrograms/dl in
      epsilon 3/4 individuals. The apo E polymorphism accounted for 7.1% of the
      interindividual variation in postprandial retinyl palmitate response, a
      contribution proportionally greater than its well-known effect on fasting LDL
      cholesterol. However, despite this effect on postprandial retinyl palmitate, the
      profile of postprandial triglyceride response was not significantly different
      among apo E genotypes. The profile of postprandial response was consistent
      between the sample of Caucasians and a smaller sample of black subjects. While
      these data indicate that the removal of remnant particles from circulation is
      delayed in subjects with the epsilon 2/3 genotype, there is no reported evidence
      that the epsilon 2 allele predisposes to coronary artery disease (CAD). The
      results of this study provide not only a reliable estimate of the magnitude of
      the effect of the apo E polymorphism on various measurements commonly used to
      characterize postprandial lipemia, but also provide mechanistic insight into the
      effects of the apo E gene polymorphism on postprandial lipemia and CAD.

PMID- 8304351
TI  - The contribution of pleiotropy to blood pressure and body-mass index variation:
      the Gubbio Study.
AB  - Blood pressure (BP), body-mass index (BMI), and quantitative phenotypes thought
      to influence BP (e.g., lithium-sodium countertransport activity) were studied in
      2,184 households comprising 5,376 people in Gubbio, Italy. Variance-components
      models were used to partition the variation of these phenotypes into components
      characterizing the effects of age-related, measured environmental, additive
      genetic, pleiotropic, unmeasured shared-household, and individual-specific (or
      random) factors. The goal of the investigation was to estimate the contribution
      of pleiotropy to variation in BP and BMI in population-based samples. Although
      our results suggest that numerous significant bivariate genetic correlations
      exist between BP and some of the traits investigated, they ultimately lead us to
      reject a prominent role for any individual bivariate pleiotropic system
      influencing the natural variation of BP. However, because we found evidence that
      many traits enter into small-impact pleiotropic relationships with BP, we cannot
      rule out the possibility that pleiotropic genes, when considered collectively,
      may contribute to BP variation at the population level. Similar results were
      obtained when BMI was taken as the primary variable of interest. We argue that
      the small but significant portion of BP variation explained by individual genes
      displaying bivariate pleiotropic effects is intuitive, in light of the relatively
      low heritabilities associated with quantitative cardiovascular phenotypes and the
      low phenotypic correlations between BP, BMI, and many other physiologically
      linked measures of cardiovascular function. Our results not only bear directly on
      both the nature of the multifactorial determinants of BP and the maintenance of
      BP variation in the population at large, but also emphasize the utility of
      variance-components models in epidemiologic and population genetics research. We
      discuss the implications of our results for genetic epidemiologists and medical
      researchers studying hypertension, as well as the limitations of our study and
      areas for future research.

PMID- 8304352
TI  - Estimating the probability for major gene Alzheimer disease.
AB  - Alzheimer disease (AD) is neuropsychiatric illness caused by multiple etiologies.
      Prediction of whether AD is genetically based in a given family is problematic
      because of censoring bias among unaffected relatives as a consequence of the late
      onset of the disorder, diagnostic uncertainties, heterogeneity, and limited
      information in a single family. We have developed a method based on Bayesian
      probability to compute values for a continuous variable that ranks AD families as
      having a major gene form of AD (MGAD). In addition, we have compared the Bayesian
      method with a maximum-likelihood approach. These methods incorporate sex- and age
      adjusted risk estimates and allow for phenocopies and familial clustering of age
      at onset. Agreement is high between the two approaches for ranking families as
      MGAD (Spearman rank [r] = .92). When either method is used, the numerical
      outcomes are sensitive to assumptions of the gene frequency and cumulative
      incidence of the disease in the population. Consequently, risk estimates should
      be used cautiously for counseling purposes; however, there are numerous valid
      applications of these procedures in genetic and epidemiological studies.

PMID- 8304353
TI  - mtDNA: Pathogenic or nonpathogenic sequence changes.

PMID- 8304354
TI  - Anticipation in mental illness.

PMID- 8304355
TI  - Lupus and antiphospholipid antibody syndrome: either, neither, or both.

PMID- 8304356
TI  - Renal artery stenosis: a common and important problem in patients with peripheral
      vascular disease.
AB  - OBJECTIVE: To study the prevalence, severity, vascular risk factors, and clinical
      implications of renal artery stenosis in patients with peripheral vascular
      disease. DESIGN: Cross-sectional study of consecutive patients who were
      electively referred from the department of vascular surgery for lower limb
      digital subtraction angiography. SETTING: St. George's Hospital, London, United
      Kingdom. SUBJECTS: One hundred twenty-seven patients presenting with intermittent
      claudication or lower limb ischemic ulceration. MAIN OUTCOME MEASURES: Prevalence
      and clinical importance of renal artery stenosis in patients with peripheral
      vascular disease adjusted for the confounding effects of age and hypertension.
      RESULTS: Of the 127 patients, 57 (44.9%) had renal artery disease, of whom 22
      (17.3%) had mild disease, 20 (15.7%) had severe disease, and 15 (11.8%) had
      bilateral renal artery stenosis. There was a significant positive relationship
      between the presence of renal artery stenosis and the severity of peripheral
      vascular disease (p = 0.00015). The risk of having renal artery stenosis was
      nearly four times greater in those with three to four vessels affected and nearly
      seven times greater in those with five or more vessels affected as compared with
      those with a milder degree of peripheral vascular disease (one or two vessels
      affected). This association persisted when the confounding effect of age and
      hypertension was accounted for. Six patients (31.6%) with renal artery stenosis
      who underwent revascularization for peripheral vascular disease died during the
      early postoperative period of cardiac or renal complications. None of the
      patients with normal renal arteries who had similar surgery developed
      postoperative complications (p = 0.005). CONCLUSIONS: Renal artery stenosis is a
      common independent feature in patients with peripheral vascular disease, and its
      prevalence increases with the increasing severity of the peripheral vascular
      disease. The postoperative risk following revascularization for peripheral
      vascular disease appears to be greater in those patients with renal artery
      stenosis. All patients studied with digital subtraction angiography for
      peripheral vascular disease should have an aortic flush performed to image the
      renal arteries. This information may be used to identify those patients likely to
      develop postoperative complications during peripheral revascularization.

PMID- 8304357
TI  - Short- and long-term prognosis of patients with a first acute myocardial
      infarction with concomitant peripheral vascular disease. SPRINT Study Group.
AB  - PURPOSE: The aim of the study was to assess the prevalence and the prognostic
      impact of concomitant peripheral vascular disease (PVD) in patients developing
      acute myocardial infarction (AMI). PATIENTS AND METHODS: Four thousand two
      hundred fifty-eight consecutive patients with a first AMI hospitalized in 13 of
      21 operating coronary care units in Israel were screened. Anamnestic,
      demographic, and medical data were collected from hospitalization charts, and all
      patients were followed clinically 1 year after discharge and up to 7 years (mean:
      5.5 years) for mortality. RESULTS: The prevalence of clinically diagnosed PVD in
      patients with a first AMI was 6.3% (269 of 4,258), with no difference between men
      and women. Patients with PVD were older (66.2 years) and included more
      hypertensive subjects (47.2%), diabetic persons (26.4%), and individuals with a
      previous history of cerebrovascular accident (CVA) (11.5%) in comparison to
      counterparts without PVD (61.7 years; 39.4%, 19.9%, and 3.3%, respectively; p <
      0.01 for each). On admission to the coronary care units, 36.5% of patients with
      PVD were in Killip class II, III, or IV versus only 18.0% in the reference group
      (p < 0.001). During hospitalization, patients with PVD exhibited a significantly
      higher rate of paroxysmal atrial fibrillation (17.5%), advanced atrioventricular
      block (15.2%), and cardiogenic shock (11.9%) in comparison to patients without
      PVD (11.9%, 10.2%, and 5.3%, respectively; p < 0.01 for each). After adjustment
      for age, gender, hypertension, history of angina, diabetes mellitus, history of
      CVA, site of infarction, and congestive heart failure on admission, the odds
      ratio for in-hospital mortality associated with PVD was 1.37 (90% confidence
      interval 1.01 to 1.83). There was no independent contribution of PVD to long-term
      (mean: 5.5 years) postdischarge mortality; the odds ratio was 1.02. CONCLUSION:
      PVD in patients with a first AMI independently increases the risk of in-hospital
      death but does not affect long-term mortality in survivors.

PMID- 8304358
TI  - Walking is related to bone density and rates of bone loss.
AB  - PURPOSE: To determine if walking, independently of other types of physical
      activity, influences bone density and rates of bone loss from the lumbar spine
      and whole body. PATIENTS AND METHODS: Healthy, white, postmenopausal women (n =
      239) participating in a 1-year, placebo-controlled trial of vitamin D
      supplementation were studied. Bone densities of the lumbar spine and whole body
      were measured semiannually by dual-energy x-ray absorptiometry. Current and
      historical participation in outdoor walking and other leisure-time physical
      activities was assessed by questionnaire. RESULTS: Women who walk more than 7.5
      miles per week had higher mean bone density of the whole body and of the legs and
      trunk regions of the body than women who walk less than 1 mile per week. The
      current level of walking activity was reflective of lifelong walking habits. The
      number of miles walked per week was also correlated with longitudinal rates of
      change in bone density at the legs (rp = 0.16, p = 0.03). CONCLUSIONS: Healthy
      postmenopausal women who walk approximately 1 mile each day have higher whole
      body bone density than women who walk shorter distances. Walking is also
      effective in slowing the rate of bone loss from the legs. These results strongly
      support the widely held belief that walking is a beneficial form of physical
      activity for maintaining skeletal integrity.

PMID- 8304359
TI  - Osteopenia in adults with cystic fibrosis.
AB  - PURPOSE: To examine the frequency and severity of osteopenia in adults with
      cystic fibrosis and the clinical variables associated with reduced bone mineral.
      PATIENTS AND METHODS: The bone mineral status of 22 white adults (14 women) with
      cystic fibrosis was compared with normative data from healthy white control
      subjects in a university medical center. Lumbar spine, femoral neck, and whole
      body bone mineral was determined by dual energy x-ray absorptiometry and
      expressed as bone mineral content (g), bone mineral density (g/cm2), and bone
      mineral apparent density (g/cm3). Bone mass was related to age, body mass,
      gonadal function, pulmonary status, and glucocorticoid exposure to identify
      variables associated with reduced bone mineral in cystic fibrosis. RESULTS: Bone
      mineral in adults with cystic fibrosis was significantly below expected values
      for age and sex at all sites using all expressions of bone mass. The mean Z-score
      was -2.8 for the lumbar spine bone density, -2.5 for the femoral neck, and -2.0
      for the whole body. Bone mineral apparent density (a term that minimizes the
      influence of bone dimensions) was also significantly reduced in patients at the
      lumbar spine (p < 0.0001) and femoral neck (p < 0.001 to p < 0.0001), indicating
      that the bone mineral deficit seen in adults with cystic fibrosis could not be
      attributed to differences in bone size. Age, weight, height, and body mass index
      were significantly correlated with bone mineral. Pulmonary status, glucocorticoid
      use, and gonadal function failed to predict bone mineral status. CONCLUSIONS:
      Osteopenia and osteoporosis occur commonly in young adults with cystic fibrosis.
      Age and body mass are predictive of bone mineral, although the pathogenesis of
      this bone mineral deficit is likely multifactorial.

PMID- 8304360
TI  - Comparison of the primary and secondary antiphospholipid syndrome: a European
      Multicenter Study of 114 patients.
AB  - PURPOSE: To determine whether the features of the antiphospholipid syndrome (APS)
      are in any way influenced by the presence or absence of systemic lupus
      erythematosus (SLE). We followed up patients with 'primary' APS (PAPS) and APS
      secondary to SLE (APS plus SLE) with the objective of comparing laboratory and
      clinical events and of determining whether patients with PAPS would have
      evolution to SLE. PATIENTS AND METHODS: A total of 114 patients from 3 European
      referral centers were included in this study. Fifty-six had APS plus SLE and 58
      had PAPS. Laboratory and clinical data were collected during an average 2-year
      period. RESULTS: Patients with PAPS and patients with APS plus SLE had similar
      clinical and laboratory profiles, with the exceptions of autoimmune hemolytic
      anemia, endocardial valve disease, neutropenia, and low C4 levels, all of which
      occurred more frequently in patients with APS plus SLE (p values: < 0.05, <
      0.005, < 0.01, and < 0.001, respectively). On follow-up, 10 thrombotic episodes
      occurred in 10 patients, 8 of whom were receiving anticoagulant therapy. No
      patient with PAPS had either anti-DNA or anti-extractable nuclear antigen
      antibodies, and these patients had a significantly lower prevalence of
      antinuclear antibodies (41%) than patients with APS plus SLE (89%). CONCLUSIONS:
      Patients with APS plus SLE and PAPS have similar clinical profiles, although
      heart valve disease, hemolytic anemia, low C4 levels, and neutropenia seem to be
      more common in patients with APS plus SLE. Patients with APS may develop further
      thrombotic events despite anticoagulation therapy.

PMID- 8304361
TI  - Osteoporosis and bone morbidity in cardiac transplant recipients.
AB  - PURPOSE: To evaluate the incidence and etiology of osteopenia and pathologic
      fractures in cardiac transplant recipients. PATIENTS: Thirty-one adult male
      cardiac transplant recipients and 14 adult men with congestive heart failure
      (CHF) awaiting cardiac transplantation. METHODS: Assessment of indices of bone
      and mineral metabolism and of bone mineral density (BMD) by dual-energy x-ray
      absorptiometry. RESULTS: BMD in the proximal femur was below normal in both
      groups compared to that in age-matched control subjects, whereas BMD in the
      lumbar spine was normal. There was no significant difference in BMD at any site
      between the two groups. No clinical parameter predicted BMD. In all patients,
      laboratory indices of bone mineral metabolism, except parathyroid hormone (PTH)
      levels, were normal and not statistically different between the two groups. CHF
      patients had a trend toward elevations of PTH, 1,25-dihydroxyvitamin D, and
      urinary calcium excretion compared to transplant patients. Eight of 31 transplant
      patients and 2 of 14 CHF patients had vertebral compression fractures (c2 = 11.8,
      p < 0.0006). Transplant recipients with fractures had twice as many rejection
      episodes as did transplant patients without fractures, but did not differ in
      cumulative dose of steroids. Two patients developed avascular necrosis of the
      femoral head following transplantation. CONCLUSIONS: Cardiac transplant
      recipients and patients with CHF awaiting transplantation had decreased hip BMD,
      but normal spine BMD. Although immunosuppressive therapy did not appear to
      influence bone mass, loop diuretics prior to transplantation may have stimulated
      a mild secondary increase in PTH that could have differentially caused loss of
      bone density at the hip in both groups. Pulse corticosteroids used in treating
      rejection may have contributed to the increased incidence of vertebral fractures
      in transplant patients. These data suggest that severe CHF with its associated
      diuretic use and decreased activity are primary contributors to osteopenia in
      these patients.

PMID- 8304362
TI  - Absence of prolonged immunosilent infection with human immunodeficiency virus in
      individuals with high-risk behaviors.
AB  - PURPOSE: The presence in some individuals of a prolonged phase of infection with
      human immunodeficiency virus type 1 (HIV-1) before seroconversion remains
      controversial. This study was undertaken to determine with a sensitive in vitro
      amplification technique, the polymerase chain reaction (PCR), whether
      seronegative individuals with high-risk behaviors could harbor HIV-1 sequences in
      their peripheral blood mononuclear cells (PBMCs) and remain seronegative for more
      than 6 months. PATIENTS AND METHODS: Seronegative individuals who engaged in
      unprotected anogenital intercourse with HIV-1-infected partners or with more than
      10 individuals per year, and seronegative individuals who shared needles with
      seropositive partners, were recruited prospectively over 18 months. HIV-1 DNA and
      RNA sequences were detected in PBMCs of these individuals with three PCR assays
      using SK38/SK39, SK145/SK431, and SK68/SK69. Seronegative but PCR-positive
      patients were also evaluated with p24 antigen capture assay,
      radioimmunoprecipitation assay, and Western blot. The latter patients were
      followed prospectively to reproduce PCR-positive results and monitor serologic
      responses. RESULTS: Sixty-one men and 18 women, with an average age of 34.1 +/-
      7.6 years, were recruited: 56 were homosexual men, 18 were heterosexual women,
      and 5 were heterosexual men. Amplification reactions for HIV-1 of 104 PBMC
      specimens from 79 patients with negative or indeterminate serologies revealed
      that 4 patients (5.1%) were positive with PCR for HIV-1 DNA and RNA at the time
      of enrollment. Positive amplification reactions could not be reproduced in
      prospective samples for one patient. The analysis of a variable human genomic
      locus in this patient's PBMCs demonstrated that the first PCR-positive sample and
      following PCR-negative samples originated from different patients, suggesting a
      specimen mix-up. Two of the three PCR-positive seronegative patients had symptoms
      suggestive of acute retroviral disease. Sera from all three patients contained
      p24 antigen. Two patients seroconverted within 1 month whereas one patient could
      not be followed prospectively. CONCLUSION: Prolonged infection with HIV-1 without
      seroconversion was not found in our population of patients at very high risk for
      HIV-1 infection. All PCR-positive patients seroconverted in less than 1 month.

PMID- 8304363
TI  - Changes of lipoprotein profile in familial dysbetalipoproteinemia with
      gemfibrozil.
AB  - PURPOSE: This prospective study was undertaken to evaluate the effects of
      gemfibrozil on the lipoprotein profile of patients with familial
      dysbetalipoproteinemia (type III hyperlipoproteinemia). PATIENTS AND METHODS:
      Eight patients with well-defined familial dysbetalipoproteinemia associated with
      the apolipoprotein (apo) E2/2 phenotype were treated with gemfibrozil (Lopid) at
      a dose of 600 mg twice daily for a period of 10 months. Blood samples were taken
      at baseline, after 4 and 5 weeks, after 3 months, and after 10 months. The
      separation of serum lipoprotein (sub)fractions was performed by a recently
      developed density gradient ultracentrifugation technique. RESULTS: After 4 weeks
      of gemfibrozil therapy, the concentrations of serum total cholesterol and serum
      total triglyceride had decreased by 45% (from 11.87 to 6.51 mmol/L, p < 0.01) and
      by 63% (from 6.08 to 2.23 mmol/L, p < 0.001), respectively. The cholesterol
      concentrations of very-low-density lipoprotein-1 (VLDL1) (large VLDL), VLDL2
      (small VLDL), and intermediate-density lipoprotein (IDL) had decreased
      significantly by 73%, 74%, and 34%, respectively. The low-density lipoprotein
      (LDL)-cholesterol level remained unchanged, whereas the particle size of LDL
      showed a small but significant increase (from 24.09 nm to 24.43 nm, p < 0.01).
      The concentrations of high-density lipoprotein (HDL)-cholesterol, apo A-I, and
      apo A-II had increased significantly by 23%, 13%, and 29%, respectively. Only
      minor changes in the composition of the lipoprotein (sub)fractions were observed.
      After 3 months of treatment with gemfibrozil, the concentrations of serum total
      cholesterol and serum total triglyceride were 5.95 mmol/L and 2.06 mmol/L,
      respectively, and after 10 months of treatment with gemfibrozil, the
      concentrations of serum total cholesterol and serum total triglyceride were 6.19
      mmol/L and 2.27 mmol/L, respectively. CONCLUSION: Gemfibrozil treatment in
      patients with familial dysbetalipoproteinemia resulted in a marked reduction of
      the concentrations of large VLDL, small VLDL, and IDL, and an increase in the
      levels of HDL, apo A-I, and apo A-II. These changes are considered to exert an
      antiatherosclerotic effect in these patients.

PMID- 8304364
TI  - Use of the alveolar-arterial oxygen gradient in the diagnosis of pulmonary
      embolism.
AB  - BACKGROUND: Arterial blood gas (ABG) values and the alveolar-arterial oxygen (A
      a) gradient are sensitive indicators of pulmonary pathology. Alone, they are not
      diagnostic of pulmonary embolism (PE), but they may be useful in excluding the
      diagnosis of PE if their values fall within the normal range. The purpose of this
      study was to determine the diagnostic value of a normal A-a gradient in ruling
      out PE. PATIENTS AND METHODS: The Derivation Set came from the records of all
      patients at Cleveland MetroHealth Medical Center who received a
      ventilation/perfusion (V/Q) scan for suspected PE in 1988 or 1989. Demographic
      and clinical data were obtained that included risk factors, symptoms, signs, and
      laboratory tests. A-a gradients were calculated using a standard equation; a
      normal gradient was defined as less than or equal to (age/4 + 4). The A-a
      gradient was examined before and after controlling for PE risk factors. The
      Validation Set was comprised of patients who had V/Q scans in 1987 and 1990.
      RESULTS: Among the 873 patients in the Derivation Set, 540 had simultaneous room
      air ABG determinations. Of these patients, 109 (20%) had a discharge diagnosis of
      PE. Only 1 of 57 (1.8%; 95% confidence interval [CI]: 0.9%-10.7%) patients
      without a history of PE or deep venous thrombosis (DVT) and with a normal A-a
      gradient had PE. Among the 805 V/Q patients in the Validation Set, 489 had
      simultaneous room air/ABG determinations. Of these, 75 (15%) had PE. Only 1 of 54
      (1.9%; 95% CI: 0.1%-11.2%) patients without a history of PE or DVT and with a
      normal A-a gradient had PE. CONCLUSIONS: A normal A-a gradient among patients
      without a history of PE or DVT makes the diagnosis of PE unlikely. Further
      diagnostic evaluation may be unnecessary in this subgroup of patients.

PMID- 8304365
TI  - Magnesium and its therapeutic uses: a review.
AB  - Magnesium has been reported as an effective medical therapy in an expanding array
      of conditions. Evidence investigating magnesium's use is presented, with a number
      of studies suggesting it should be seriously considered in such conditions as
      ischemic heart disease, cardiac arrhythmias, and asthma. Magnesium balance and
      metabolism are briefly reviewed, and then various hypotheses are presented that
      may explain magnesium's physiologic mechanisms of action, most likely involving
      calcium and potassium flux across cellular membranes in smooth muscle. In a
      number of the conditions to be discussed, it has been uncertain whether magnesium
      administration serves the purpose of merely correcting an underlying deficiency
      state or of utilizing a specific pharmacologic effect of magnesium. Magnesium
      deficiency is a relatively common condition, and predisposing factors as well as
      recent methods for assessing total body stores of magnesium are discussed.
      Physicians should be familiar with the numerous conditions and therapeutics that
      are risk factors for an underlying magnesium deficiency and in which empiric
      magnesium replacement should be considered. Guidelines for administration of
      parenteral magnesium are presented with specific focus on the low risk of adverse
      effects, as suggested by the large and rapid dosing regimens used in many of the
      clinical studies discussed here.

PMID- 8304367
TI  - Frozen shoulder triggered by cardiac catheterization via the brachial artery.

PMID- 8304366
TI  - Efficacy and safety of atenolol, enalapril, and isradipine in elderly
      hypertensive women.
AB  - PURPOSE: This trial was designed to evaluate the efficacy and safety of three
      different classes of antihypertensive agents in elderly women. PATIENTS AND
      METHODS: The trial had three phases: 4 to 8 weeks of placebo, 6 weeks of
      titration, and 16 weeks of maintenance. White women between 60 and 80 years old
      with sitting diastolic blood pressures (DBPs) from 95 through 114 mm Hg treated
      with placebo were evaluated by history, physical examination, laboratory studies,
      and quality-of-life interview. After double-blind randomization with low-dose
      atenolol, enalapril, or isradipine, the dose was increased stepwise and
      hydrochlorothiazide added as needed to achieve goal DBP (less than 90 mm Hg and
      greater than 10 mm Hg below baseline). During maintenance, patients not at goal
      were "stepped up," and patients with uncontrolled DBP at maximum dosage were
      removed from the study. The pretreatment (baseline) blood pressure of the 315
      randomized participants averaged 161/100 mm Hg; 92% had been treated previously
      for hypertension, 15% had diabetes mellitus, 11% smoked, and 38% consumed
      alcohol. RESULTS: For 245 patients completing the trial, the average decrease in
      blood pressure during treatment was 18.2/15.6 mm Hg. Antihypertensive efficacy
      was similar for the monotherapy drug regimens, with 84%, 71%, and 80% of patients
      receiving atenolol, enalapril, and isradipine, respectively, achieving DBP goal.
      Of the 70 patients who did not complete the trial, 42 left because of symptoms
      and 19 because of uncontrolled DBP. No important, unexpected drug-induced changes
      in symptoms or blood chemistries were noted. Symptom frequency differed little
      among the three dosage levels, becoming maximal by the second visit at the same
      dosage level. CONCLUSION: All three drugs lowered DBP comparably, and none
      produced alarming effects. Thirteen percent of patients left the study because of
      symptoms.

PMID- 8304368
TI  - Graded venesection in the management of erythrocytosis: a clinicophysiologic
      study.

PMID- 8304369
TI  - Congenital afibrinogenemia and splenic rupture.

PMID- 8304370
TI  - Clostridium difficile colitis associated with trimethoprim-sulfamethoxazole given
      as prophylaxis for Pneumocystis carinii pneumonia.

PMID- 8304372
TI  - Support urged for needle exchange programs.

PMID- 8304371
TI  - Pyrimethamine alone as long-term suppressive therapy in cerebral toxoplasmosis.

PMID- 8304373
TI  - Beware of labels.

PMID- 8304374
TI  - Dialysis can raise BP.

PMID- 8304375
TI  - Measure of potency.

PMID- 8304376
TI  - Minims aren't units.

PMID- 8304377
TI  - Misinterpreting written orders.

PMID- 8304379
TI  - Caring for the family left behind.

PMID- 8304378
TI  - Acute SCI. How to minimize the damage.

PMID- 8304380
TI  - Digoxin toxicity. Ventricular dysrhythmias to watch for.

PMID- 8304381
TI  - Two legs to stand on.

PMID- 8304382
TI  - Reversing pulmonary edema.

PMID- 8304383
TI  - Giving and taking criticism.

PMID- 8304384
TI  - Why not let staff nurses defibrillate?

PMID- 8304385
TI  - Worthy of Robert's gift.

PMID- 8304386
TI  - Antibiotic gets FDA nod for MAC treatment.

PMID- 8304387
TI  - Diagnostic tests for abdominal trauma.

PMID- 8304388
TI  - MRI madness.

PMID- 8304389
TI  - A well-informed patient is a valuable asset.

PMID- 8304390
TI  - More patient education tips.

PMID- 8304391
TI  - 10 commonly asked questions about diabetes.

PMID- 8304392
TI  - The right tool for the job.

PMID- 8304393
TI  - Giving fentanyl for pain outside the OR.

PMID- 8304394
TI  - The truth-tellers. How hospice nurses help patients confront death.

PMID- 8304395
TI  - Letters from Carol.

PMID- 8304396
TI  - Understanding prophylactic therapy for HIV infections.

PMID- 8304397
TI  - How to manage patients with a Roux-en-Y jejunostomy.

PMID- 8304398
TI  - Test your knowledge of tracheostomy tubes.

PMID- 8304399
TI  - Fast action for splenic rupture.

PMID- 8304400
TI  - I deal with life.

PMID- 8304401
TI  - Taking orders from a CNM.

PMID- 8304402
TI  - Trouble teaching TPN.

PMID- 8304403
TI  - Concealing a med error.

PMID- 8304404
TI  - Rehabilitation nursing: a client-centered philosophy.

PMID- 8304405
TI  - Deferring to the dying.

PMID- 8304406
TI  - Personal hardiness: your buffer against burnout.

PMID- 8304407
TI  - The ultimate price.

PMID- 8304408
TI  - Biological applications of atomic force microscopy.
AB  - The newly developed atomic force microscope (AFM) provides a unique window to the
      microworld of cells, subcellular structures, and biomolecules. The AFM can image
      the three-dimensional structure of biological specimens in a physiological
      environment. This enables real-time biochemical and physiological processes to be
      monitored at a resolution similar to that obtained for the electron microscope.
      The process of image acquisition is such that the AFM can also measure forces at
      the molecular level. In addition, the AFM can interact with the sample, thereby
      manipulating the molecules in a defined manner--nanomanipulation! The AFM has
      been used to image living cells and the underlying cytoskeleton, chromatin and
      plasmids, ion channels, and a variety of membranes. Dynamic processes such as
      crystal growth and the polymerization of fibrinogen and physicochemical
      properties such as elasticity and viscosity in living cells have been studied.
      Nanomanipulations, including dissection of DNA, plasma membranes, and cells, and
      transfer of synthetic structures have been achieved. This review describes the
      operating principles, accomplishments, and the future promise of the AFM.

PMID- 8304409
TI  - Na(+)-H+ antiporter activity in relation to membrane fatty acid composition and
      cell proliferation.
AB  - Na(+)-H+ exchange activity was studied in a human breast cancer cell line. At
      steady state, the intracellular pH (pHi) of the cells was 7.23 +/- 0.01, and
      intracellular buffering capacity (beta i) was 44 +/- 4 mM/pH unit. pHi was
      controlled by a Na(+)-H+ antiporter that was reversible, electroneutral,
      inhibited by 5-(N-methyl-N-isobutyl)amiloride, and dependent on extracellular
      Na+. The exchanger function depended on internal H+ concentration, according to
      an allosteric activation mechanism obeying the model of Hill. The exchanger was
      inactive at pHi > or = 7.22, and its maximal activity was reached at pHi < 6.60.
      The exchanger was stimulated by osmotic shrinking but was unaffected by growth
      factors (epidermal growth factor, insulin-like growth factor I) or by serum. When
      cells were grown in a medium supplemented with linoleic or alpha-linolenic acids,
      large quantities of the additional fatty acid accumulated in membranes, saturated
      fatty acids increased, and monounsaturated fatty acids decreased. These changes
      reduced cell proliferation but had no effect on the steady-state value of pHi, on
      beta i, or on the kinetic parameters of the Na(+)-H+ exchanger. Therefore, in
      this system, cell proliferation is not directly related to the activation of the
      Na(+)-H+ exchanger.

PMID- 8304410
TI  - Permeability properties of rat renal lysosomes.
AB  - Although lysosomes maintain large pH gradients and may be subjected to
      significant osmotic gradients in vivo, little is known about their passive
      permeability properties. In recent studies, vacuolar H(+)-adenosine
      triphosphatases (ATPases), such as those found in lysosomes, have been suggested
      to act as water channels. In addition, the erythrocyte and proximal tubule water
      channel CHIP28 is present on the plasma membrane of proximal tubule cells and may
      undergo endocytosis so that it is incorporated in lysosomes. We therefore
      examined water, proton, and small nonelectrolyte permeabilities in freshly
      purified lysosomes from rat renal proximal tubule. Lysosomes were purified by
      differential and Percoll gradient centrifugation. The preparation contained only
      lysosomes when examined by electron microscopy. Moreover, analysis by flow
      cytometry showed virtually all particles to be positive for acid phosphatase and
      cathepsin B activities. Permeabilities were measured on a stopped-flow
      fluorimeter by monitoring the self-quenching or pH-sensitive quenching of
      entrapped fluorescein derivatives. Osmotic water permeability (Pf) averaged 0.011
      +/- 0.003 cm/s (n = 6), a value similar to that of biological membranes
      containing water channels. However, Pf was insensitive to the organic mercurial
      reagent p-chloromercuribenzene-sulfonate and to HgCl2 and exhibited an activation
      energy of 10.8 +/- 0.8 kcal/mol. These results indicate that water flux in
      lysosomes occurred via the lipid bilayer, and not via water channels. Addition of
      ATP led to lysosomal acidification (proton flux = 4.6 +/- 0.8 x 10(-11) mmol H+.s
      1.cm-2), which was completely inhibited by 0.1 microM bafilomycin. Pf was
      insensitive to this agent as was the passive proton permeability (0.36 +/- 0.18
      cm/s, n = 4). Permeabilities to small nonelectrolytes varied in proportion to the
      oil-water partition coefficient, confirming the applicability of Overton's rule
      to lysosomes. We conclude that proximal tubular lysosomes exhibit high Pf, which
      occurs via the lipid bilayer and not via vacuolar H(+)-ATPase.

PMID- 8304411
TI  - Involvement of protein kinase C in macrophage activation by poly(I.C).
AB  - The expression of cytocidal activity is initiated by the interaction of
      macrophages with priming [e.g., interferon (IFN)] and triggering stimuli
      (polyinosinic-polycytidylic acid). We have shown that the triggering step can be
      initiated in a Ca(2+)-dependent fashion and hypothesized that protein kinase C
      (PKC) may couple the Ca2+ signal to the expression of a gene product, Bf, that
      accompanies the expression of macrophage cytocidal activity. Exposure of IFN
      primed macrophages to polyinosinic-polycytidylic acid in the presence of the PKC
      inhibitors H-7 or sphingosine or after downregulation of PKC with phorbol
      myristate acetate markedly inhibited Bf synthesis. Western blots of macrophage
      lysates revealed the presence of the alpha-, delta-, and zeta-isozymes of PKC,
      and all were found to be downregulated by phorbol myristate acetate. Inhibition
      of PKC also prevented the increase in IFN-beta mRNA levels and partially blocked
      the response to IFN-beta. These data suggest that the alpha-, delta-, and zeta
      isozymes of PKC are involved in signaling leading to Bf expression and that the
      level of involvement is restricted to the induction and response to IFN-beta.

PMID- 8304412
TI  - Polyadenylation of Na(+)-K(+)-ATPase beta 1-subunit during early development of
      Xenopus laevis.
AB  - In fully grown Xenopus oocytes, the synthesis of beta-subunits is limiting for
      the formation of functional Na(+)-K(+)-adenosinetriphosphatase alpha/beta
      complexes (Geering, K. FEBS Lett. 285: 189-193, 1991). In the present study, we
      show that during oocyte growth (from stage I to stage VI) alpha 1-, but not beta
      1- or beta 3-isoform, mRNAs accumulate. In addition, beta-mRNAs are apparently
      sequestered in an untranslated pool in fully grown oocytes (stage VI). From
      fertilization to morulation, the total pools of alpha 1-, beta 1-, or beta 3
      mRNAs vary little. Whereas polyadenylated [poly(A)+] alpha 1- and beta 3-isoform
      mRNAs did not change significantly, poly(A)+ beta 1-mRNA abundance increased
      three- to fourfold at morulation, accompanied by a parallel increase in beta 1
      protein synthesis. After midblastula transition (i.e., at early gastrula) and
      during neurulation, poly(A)+ alpha 1- and beta 3-mRNAs accumulated rapidly,
      whereas poly(A)+ beta 1-mRNA accumulation was delayed by approximately 2 h,
      beginning only at early neurula. Our results indicate that 1) the abundance of
      poly(A)+ beta 1-mRNA is rate limiting during embryonic development for the
      assembly of alpha 1/beta 1-heterodimers, shown to be involved in the vectorial
      transport of sodium in kidney cells, and 2) the polyadenylation of beta 1-mRNA is
      a rate-limiting factor during morulation for the synthesis and assembly of new
      sodium pumps at the time of blastocoel fluid formation. The 3'-untranslated
      region of beta 1-mRNA (but not of alpha 1-mRNA) expresses cytoplasmic
      polyadenylation elements (CPEs) with the consensus sequence AXX
      AUUUU(A/U)(A/U)(A/U). A role of CPE in the differential polyadenylation of alpha
      1- and beta 1-mRNA is proposed.

PMID- 8304413
TI  - Regulatory volume decrease in cultured astrocytes. I. Potassium- and chloride
      activated permeability.
AB  - Regulatory volume decrease (RVD) in detached cerebellar astrocytes in culture
      after acute exposure to hyposmolarity was characterized in this and the
      accompanying paper [H. Pasantes-Morales, R. A. Murray, R. Sanches-Olea, and J.
      Moran. Am. J. Physiol. 266 (Cell Physiol. 35): C172-C178, 1994]. RVD was
      independent of extracellular calcium, was accelerated at pH 8-9 and retarded at
      pH 6, and was reduced at temperatures < 18 degrees C. The cationic pathway
      activated by hyposmolarity was specific for K+ and Rb+, since RVD was abolished
      and secondary swelling occurred when these ions replaced Na+. However, Li+,
      choline, tris(hydroxymethyl)aminomethane, and glucosamine, all as Cl- salts, did
      not affect RVD. The anion pathway was unselective, since RVD was inhibited when
      NaCl was replaced by anion K+ salts with a permeability rank of SCN- = I- > NO3-
      > Cl- > benzoate > acetate >> SO3- > gluconate. RVD was unaffected by bumetanide
      (50 microM) and weakly inhibited by furosemide (2 mM). Quinidine but not other K+
      channel blockers inhibited RVD, and its effect was reversed by gramicidin. RVD
      was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and
      dipyridamole but not by diphenylamine-2-carboxylate or anthracene-9-carboxylate.
      These results suggest that diffusion possibly via channels rather than
      cotransporters is involved in the swelling-activated K+ and Cl- fluxes.
      Gramicidin did not change astrocyte volume in isosmotic conditions, but greatly
      accelerated RVD, suggesting that low Cl- permeability in isosmotic conditions
      markedly increases by swelling, thus making K+ permeability the rate-limiting
      step for RVD.

PMID- 8304414
TI  - Regulatory volume decrease in cultured astrocytes. II. Permeability pathway to
      amino acids and polyols.
AB  - The permeability of the hyposmolarity-activated pathway to amino acids and
      polyols in cultured astrocytes was examined following the change in rate and
      direction of regulatory volume decrease (RVD) when the extracellular
      concentration of the osmolytes was increased to reverse their intracellular
      extracellular concentration gradient. Activation of the pathway by swelling would
      allow those permeable osmolytes to enter the cell and inhibit RVD. The pathway
      was found to be permeable to neutral amino acids, with beta-amino acids (beta
      alanine = taurine > gamma-aminobutyric acid) more permeable than alpha-amino
      acids. Glycine, alanine, threonine, phenylalanine, and asparagine, but not
      glutamine, were permeable through this pathway. Aspartate was more permeable than
      glutamate, and K+ and not Na+ must be the accompanying cation. Basic amino acids
      were excluded. The dimension of the amino acid pore activated by hyposmolarity
      seems to be at the limit of glutamate-glutamine size. Influx rather than efflux
      of amino acids was observed when extracellular concentration was greater than
      intracellular concentration, with differences in the amount accumulated by cells
      correlating with their efficiency as RVD blockers. Influx of taurine (as
      representative of permeable amino acids) was inhibited by the Cl- channel
      blockers/exchangers 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (40%) and
      dipyridamole (85%) , and it is suggested that amino acids permeate through an
      anion channel. Sorbitol and mannitol, but not inositol, exhibited a small
      inhibitory effect on the later phase of RVD, whereas inositol slightly
      accelerated RVD.

PMID- 8304415
TI  - Hydroperoxide-induced oxidative stress impairs heart muscle cell carbohydrate
      metabolism.
AB  - Hydrogen peroxide (H2O2) may incite cardiac ischemia-reperfusion injury. We
      evaluate herein the influence of H2O2-induced oxidative stress on heart muscle
      hexose metabolism in cultured neonatal rat cardiomyocytes, which have a substrate
      preference for carbohydrate. Cardiomyocyte exposure to 50 microM-1.0 mM bolus
      H2O2 transiently activated the pentose phosphate cycle and thereafter inhibited
      cellular glucose oxidation and glycolysis. These metabolic derangements were
      nonperoxidative in nature (as assessed in alpha-tocopherol-loaded cells) and
      occurred without acute change in cardiomyocyte hexose transport or
      glucose/glycogen reserves. Glycolytic inhibition was supported by the rapid,
      specific inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The
      degree of GAPDH inhibition correlated directly with the magnitude of the
      oxidative insult and was independent of both metal-catalyzed H2O2 reduction to
      free radicals and lipid peroxidation. Severe GAPDH inhibition was required for a
      rate-limiting effect on glycolytic flux. Cardiomyocyte pyruvate dehydrogenase was
      also inhibited by H2O2 overload, but to a lesser degree than GAPDH such that
      entry of hexose-derived acetyl units into the tricarboxylic acid cycle was not as
      restrictive as GAPDH inactivation to glycolytic ATP production. An increase in
      phosphofructokinase activity accompanied GAPDH inactivation, leading to the
      production and accumulation of glycolytic sugar phosphates at the expense of ATP
      equivalents. Cardiomyocyte treatment with iodoacetate or 2-deoxyglucose indicated
      that GAPDH inactivation/glycolytic blockade could account for approximately 50%
      of the maximal ATP loss following H2O2 overload. Partial restoration of GAPDH
      activity after a brief H2O2 "pulse" afforded some ATP recovery. These data
      establish that specific aspects of heart muscle hexose catabolism are H2O2
      sensitive injury targets. The biochemical pathology of H2O2 overload on
      cardiomyocyte carbohydrate metabolism has implications for post-ischemic cardiac
      bioenergetics and function.

PMID- 8304416
TI  - Inhibition of Na(+)-K(+)-ATPase activates Na(+)-K(+)-2Cl- cotransporter activity
      in cultured ciliary epithelium.
AB  - Inhibition of Na(+)-K(+)-ATPase activates Na(+)-K(+)-2Cl- cotransporter activity
      in cultured ciliary epithelium. Am. J. Physiol. 266 (Cell Physiol. 35): C198
      C205, 1994.--86Rb uptake experiments were conducted to measure Na(+)-K(+)-ATPase
      activity and Na(+)-K(+)-2Cl- cotransporter activity in a cell line derived from
      rabbit nonpigmented ciliary epithelium. The presence of a Na(+)-K(+)-2Cl-
      cotransporter was supported by the observation of a bumetanide-sensitive 86Rb
      uptake component that was dependent on the extracellular concentration of both
      sodium and chloride. Potassium influx mediated by the Na(+)-K(+)-2Cl-
      cotransporter and Na(+)-K(+)-ATPase accounted for approximately 46 and 33% of
      total potassium uptake, respectively, whereas both ouabain- and bumetanide
      resistant uptake accounted for 9%. Inhibition of the Na(+)-K(+)-ATPase had a
      stimulatory effect on Na(+)-K(+)-2Cl- cotransporter activity, which was dependent
      on the extent and duration of Na(+)-K(+)-ATPase inhibition. Ouabain treatment
      stimulated the potassium (86Rb) efflux rate and reduced intracellular potassium
      ([K]i). Potassium channel blockers suppressed the ouabain-activated potassium
      efflux and inhibited the ouabain-induced activation of the Na(+)-K(+)-2Cl-
      cotransporter. We conclude that Na(+)-K(+)-ATPase inhibition leads to the opening
      of potassium channels, which exacerbates the depletion of cellular potassium;
      Na(+)-K(+)-2Cl- cotransporter stimulation caused by the fall of [K]i overrides
      the tendency of increased cellular sodium to inhibit the cotransporter.

PMID- 8304417
TI  - Basic FGF activates phospholipase D in endothelial cells in the absence of
      inositol-lipid hydrolysis.
AB  - In the absence of inositol-lipid hydrolysis, mitogenic concentrations of basic
      fibroblast growth factor (bFGF) stimulated phosphatidylbutanol formation in the
      presence of butan-1-ol in [3H]myristate-labeled human umbilical vascular
      endothelial (HUVE) cells, indicating that the fibroblast growth factor receptor
      was able to couple to the activation of phospholipase D (PLD). The ability of
      bFGF and 12-O-tetradecanoylphorbol-13-acetate (TPA) to stimulate PLD activity was
      completely abolished in cells pretreated with 400 nM TPA for 48 h to downregulate
      protein kinase C (PKC). bFGF-stimulated PLD activity was inhibited by genistein
      (5 microM; P < 0.02) and the PKC inhibitor 1-(5-isoquinolinylsulfonyl)-2
      methylpiperazine (H-7, 5 microM; P < 0.001) as well as by the removal of calcium
      from extracellular environment. bFGF induced DNA synthesis in a dose-dependent
      manner, and pretreatment of cells with H-7 inhibited the mitogenic activity of
      bFGF. These results indicate that activation of PKC is responsible for bFGF
      induced PLD activation and the mitogenic activity of bFGF in HUVE cells. A
      coupled PLD/3-sn-phosphatidate phosphohydrolase pathway may play a role in the
      regulation of endothelial cell proliferation.

PMID- 8304418
TI  - Regulation of intracellular free Mg2+ and contraction in single adult mammalian
      cardiac myocytes.
AB  - Studies in isolated cardiac myocytes have increased our understanding of
      intracellular Ca2+ regulation. Because less is known about Mg2+ regulation, adult
      rat ventricular myocytes were loaded with the Mg(2+)-sensitive fluorescent probe
      mag-indo 1, and changes in intracellular Mg2+ concentration ([Mg2+]i) and cell
      length were examined under a variety of conditions. The fluorescent signal was
      calibrated intracellularly and found to differ slightly from that for the probe
      in solution. Roughly 40% of the signal was intramitochondrial; the remainder was
      localized in the cytosol. Basal [Mg2+]i averaged 1.02 +/- 0.03 mM (n = 53 cells).
      No change in [Mg2+]i was observed during a single electrically stimulated
      contraction, and only a minor increase was seen during rapid electrical
      stimulation, which was expected to raise intracellular Ca2+ concentration
      ([Ca2+]i) to approximately 1 microM. An acid shift in intracellular pH of
      approximately 1 pH unit was accompanied by a small change in [Mg2+]i (0.34 +/-
      0.03 mM, n = 6, P < 0.05). No change in [Mg2+]i was observed when cells were
      superfused with 15 mM Mg2+, despite marked changes in contraction. [Mg2+]i more
      than doubled when cells were depleted of ATP by exposure to hypoxia or metabolic
      inhibitors. The increase in [Mg2+]i was abrupt and occurred at the time of the
      failure of contraction, plateauing as rigor contracture developed. Reoxygenation
      was accompanied by a gradual fall in [Mg2+]i in cells that recovered mechanical
      function, and in a subset of cells that underwent hypercontracture. Studies in
      cell suspensions confirmed that rapid cellular energy depletion was accompanied
      by increases in [Mg2+]i and parallel decreases in ATP. Thus [Mg2+]i was largely
      insensitive to changes in [Ca2+]i or pHi and extracellular [Mg2+] but was rapidly
      altered by changes in energy state in a manner that was related to specific
      changes in cell morphology and contractile function.

PMID- 8304419
TI  - Na(+)-Ca2+ exchanger in arteries: identification by immunoblotting and
      immunofluorescence microscopy.
AB  - Antibodies raised against dog cardiac Na(+)-Ca2+ exchanger were employed to
      determine the presence and distribution of the exchanger in arterial smooth
      muscle (ASM) cells. The antiserum cross-reacted with protein bands of
      approximately 70, 120, and 150-160 kDa from the membranes of ASM cells, as well
      as heart sarcolemma. A cardiac Na(+)-Ca2+ exchanger cDNA probe hybridized to 7
      kilobase (kb) mRNA from myocytes of the mesenteric artery. Thus ASM cells possess
      a "cardiac type" Na(+)-Ca2+ exchanger. The relative amounts of 7-kb mRNA and
      antigen detected on Northern and Western blots, respectively, however, indicate
      that vascular myocytes contain much less of this transporter than do cardiac
      myocytes. Immunofluorescence studies on cultured arterial myocytes suggest that
      the exchanger molecules are organized in reticular patterns over the cell
      surfaces. A similar pattern is observed when cells are stained for sarcoplasmic
      reticulum (SR) Ca(2+)-ATPase. This raises the possibility that the exchanger in
      the plasmalemma of arterial myocytes may be associated, perhaps functionally as
      well as structurally, with the underlying SR. The antiserum also cross-reacted
      with endothelial cell membranes, but labeling was lighter and more diffuse than
      in the myocytes.

PMID- 8304420
TI  - Epidermis contains platelet-type 12-lipoxygenase that is overexpressed in
      germinal layer keratinocytes in psoriasis.
AB  - Human epidermal cells exhibited none of the cytosolic lipoxygenase activity that
      is prominent in mucosal epithelial cells, but instead contained a microsomal
      activity that converted arachidonic acid to 12-hydroxyeicosatetraenoic acid (12
      HETE). Identification of the extractable 12-HETE-forming activity as a 12
      lipoxygenase (distinct from cytochrome P-450) included (S)-12-stereospecificity
      of product formation, trapping of 12-hydroperoxyeicosatetraenoic acid as an
      intermediate reaction product, and lack of NADPH dependence for activity.
      Epidermal cell poly(A)+ RNA contained high levels of a 2.3-kb mRNA that
      selectively hybridized with human platelet 12-lipoxygenase cDNA, and partial cDNA
      sequence of this mRNA indicated identity to platelet 12-lipoxygenase. The
      epidermal 12-lipoxygenase was not recognized by antibodies against the leukocyte
      type 12- and 15-lipoxygenases (found in leukocytes, reticulocytes, and mucosal
      epithelial cells) but was detected by an antiplatelet 12-lipoxygenase antibody.
      The epidermal 12-lipoxygenase antigen was selectively expressed in germinal layer
      keratinocytes in healthy and psoriatic skin, and these layers exhibited
      hyperplasia and increased immunostaining in inflamed psoriatic skin. Together
      with previous results, these observations indicate that 1) epidermis generates 12
      HETE by either cytochrome P-450 or lipoxygenase-based mechanisms depending on
      reaction conditions, and 2) 12-lipoxygenases (originally described in
      hematopoietic cell types) may be expressed in at least two distinct isoforms in
      epithelial barriers in humans, and in the case of the skin, a microsomal
      (platelet-type) 12-lipoxygenase is selectively overexpressed in germinal layer
      keratinocytes during psoriatic inflammation.

PMID- 8304421
TI  - PGE2: a mediator of corneal endothelial wound repair in vitro.
AB  - Maintenance of the integrity of the corneal endothelial monolayer is essential
      for corneal clarity. Aging, trauma, inflammation, and diseases, such as diabetes,
      can compromise monolayer integrity, resulting in corneal edema and loss of visual
      acuity. In adult humans, repair of the monolayer occurs mainly by two forms of
      cell movement: "migration," in which individual cells move from the wound edge to
      repopulate the defect, and "spreading," in which cells enlarge and flatten,
      causing movement of the monolayer as a sheet to cover the defect. Previous
      studies from this laboratory have shown that these two forms of movement can be
      pharmacologically separated. In the current studies, an established tissue
      culture model was used to determine the effect of prostaglandin E2 (PGE2) and of
      mediators of the adenosine 3',5'-cyclic monophosphate (cAMP) pathway on
      individual cell migration. Indomethacin, an inhibitor of prostaglandin synthesis,
      significantly decreased individual cell migration below levels obtained when
      wounds were exposed to culture medium alone. PGE2, but not PGF2 alpha, restored
      this response in a dose-dependent manner. In the presence of indomethacin,
      forskolin, a direct adenylate cyclase activator, stimulated individual cell
      migration. 2',5'-Dideoxyadenosine, an adenylate cyclase inhibitor, reversed the
      stimulatory effects of both forskolin and PGE2. Dibutyryl cAMP (DBcAMP) also
      stimulated individual cell migration in the presence of indomethacin, whereas,
      H89, a protein kinase A inhibitor, reversed both the DBcAMP and PGE2-induced
      effects. These results provide evidence that stimulation of the cAMP pathway
      enhances individual cell migration and that PGE2, acting via this pathway, may be
      an endogenous stimulator of this response during corneal endothelial wound
      repair.

PMID- 8304422
TI  - Ca2+ stores in smooth muscle cells: Ca2+ buffering and coupling to AVP-evoked
      inositol phosphate synthesis.
AB  - Cytosolic Ca2+ concentrations ([Ca2+]cyt) and [3H]inositol phosphates ([3H]InsP)
      were correlated while decreasing the Ca2+ content of sarcoplasmic reticulum (SR)
      stores in cultured A7r5 cells at rest and after activation with 8-arginine
      vasopressin (AVP). Decreasing Ca2+ influx by reducing extracellular Ca2+ or by
      treatment with verapamil had no effect on resting [Ca2+]cyt but significantly
      inhibited the AVP-evoked Ca2+ transients (delta Ca2+). Neither treatment affected
      basal [3H]InsP, but both treatments increased AVP-evoked synthesis of [3H]InsP.
      Likewise, basal [3H]InsP were unaffected by brief (10-30 s) exposures to
      thapsigargin (TG), while AVP-induced [3H]InsP synthesis was significantly
      augmented. Similar treatment with TG rapidly increased resting [Ca2+]cyt and
      decreased SR Ca2+ by 9-25% as manifested by decreased delta Ca2+. By contrast,
      ryanodine induced slow increases in [Ca2+]cyt that stabilized within 30 min;
      subsequent AVP-induced delta Ca2+ were attenuated by 50%. Ryanodine had no effect
      on either basal or stimulated [3H]InsP levels. Agents that elevate adenosine
      3',5'-cyclic monophosphate (cAMP) such as caffeine, 8-bromo-cAMP, and forskolin
      inhibited AVP-evoked [3H]InsP formation. These observations provide further
      characterization of a communication pathway between the AVP-sensitive Ca2+ stores
      in the SR and the plasmalemmal enzyme system involved in the synthesis of
      inositol 1,4,5-trisphosphate. This pathway is manifested by an inverse
      relationship between the Ca2+ content of an AVP-sensitive, ryanodine-insensitive
      SR Ca2+ store and evoked [3H]InsP synthesis and may represent an important
      component in the tonic regulation of resting [Ca2+]cyt and vasoconstrictor- and
      hormone-evoked SR Ca2+ release.

PMID- 8304423
TI  - Characterization of the endogenous Na(+)-K(+)-2Cl- cotransporter in Xenopus
      oocytes.
AB  - Over time, Xenopus laevis changed from producing stage V and VI oocytes with
      little native Na(+)-K(+)-2Cl- cotransport activity to those with substantial
      activity. In oocytes with high endogenous activity, K+ uptake, using the tracer
      86Rb+ was approximately 20 pmol.min-1.oocyte-1 in the presence of blockers of
      Na(+)-K(+)-ATPase and conductive K+ transport. Bumetanide (10 microM) inhibited >
      90% of this uptake, suggesting involvement of Na(+)-K(+)-2Cl- cotransport. This
      was confirmed by two observations that are found in this cotransporter in other
      tissues: 1) The related diuretics, thiobenzmetanide [50% inhibitory concentration
      (IC50), 2 x 10(-11) M] > bumetanide (IC50, 7 x 10(-8) M) > furosemide (IC50, 2.5
      x 10(-6) M) inhibited the cotransporter in a dose-dependent manner. 2) There was
      little uptake of K+ in the absence of extracellular Na+ or Cl-. Halving medium
      osmolarity to 92 mosM decreased bumetanide-sensitive K+ uptake by approximately
      75%, whereas a doubling of medium osmolarity increased it by approximately 50%.
      The cotransport activity was increased fourfold by the phosphatase inhibitor
      calyculin A (200 nM) but was unaffected by 8-(4-chlorophenylthio)adenosine 3',5'
      cyclic monophosphate, 8-bromoguanosine 3',5'-cyclic monophosphate, ATP,
      ionomycin, or okadaic acid. Both the photoaffinity bumetanide analogue, 4
      [3H]benzoyl-5-sulfamoyl-3-(3-thenyloxy)benzoic acid, and an antiserum raised
      against Ehrlich ascites cell cotransporter specifically labeled an approximately
      140-kDa oocyte membrane protein. These results demonstrated that, in addition to
      the Na+ pump and K+ channels, K+ uptake in Xenopus oocytes occurs via a loop
      diuretic-sensitive Na(+)-K(+)-2Cl- cotransporter.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8304424
TI  - Impaired cardiac function in rats with healed myocardial infarction: cellular vs.
      myocardial mechanisms.
AB  - The inotropic responsiveness of isolated perfused rat hearts and single left
      ventricular (LV) myocytes to extracellular Ca2+ ([Ca2+]o) was examined 3 wk after
      ligation of left main coronary artery. Myocytes isolated from myocardial
      infarcted (MI) hearts were 10% longer. At [Ca2+]o of 1.1 mM, cell shortening as
      well as intracellular Ca2+ concentration dynamics were similar between MI and
      sham LV myocytes. At [Ca2+]o of 4.9 mM, maximal extent of cell shortening was
      significantly less in MI myocytes (16 +/- 1 vs. 22 +/- 1%), and peak
      intracellular Ca2+ concentration was also substantially lower. Thus, under
      conditions of high [Ca2+]o, decreased sarcolemmal Ca2+ influx and Ca2+ release
      during excitation-contraction may contribute to systolic dysfunction in MI
      hearts. Perfused working hearts and isovolumic heart preparations with infarcted
      LV displayed depressed maximal systolic pressure and decreased sensitivity to the
      inotropic effects of [Ca2+]o. Our data also indicate that, in addition to
      possible abnormalities in the contractile response of single myocytes, global
      factors such as loss of functional myocardium, altered chamber geometry, tissue
      fibrosis, and/or subendocardial ischemia contributed to depressed LV function in
      post-MI hearts perfused at physiological [Ca2+]o.

PMID- 8304425
TI  - A model for the propagation of intercellular calcium waves.
AB  - In response to mechanical stimulation of a single cell, intercellular Ca2+ waves
      propagate through airway epithelial and glial cell cultures, providing a
      mechanism for intercellular communication. Experiments indicate that
      intercellular propagation of the Ca2+ wave is mediated by the movement of
      inositol 1,4,5-trisphosphate (IP3) through gap junctions. To explore the validity
      of this hypothesis, we have constructed and solved a system of partial
      differential equations that models the Ca2+ changes induced by the movement of
      IP3 between cells. The model is in good qualitative agreement with experimental
      data, including the behavior of the wave in the absence of extracellular Ca2+,
      the shape of the subsequent asynchronous Ca2+ oscillations, and the passage of a
      wave through a cell exhibiting Ca2+ oscillations. However, the concentration of
      IP3 that is required in each cell to propagate the wave may not be achieved by
      passive diffusion of IP3 through gap junctions from the stimulated cell. We
      therefore suggest that Ca(2+)-independent regenerative production of IP3 might be
      necessary for the propagation of intercellular Ca2+ waves.

PMID- 8304426
TI  - A confocal laser scanning microscope designed for indicators with ultraviolet
      excitation wavelengths.
AB  - In this paper we describe the modifications necessary to upgrade, at affordable
      cost, a commercially available confocal laser scanning microscope for use with
      ultraviolet (UV) excitation. The optical problems associated with these
      modifications are described in detail, and easy solutions to solve them are
      suggested. The optical resolution of the instrument was tested with fluorescent
      beads and was found to be close to diffraction limited. The light losses due to
      lateral chromatic aberration were assessed in a thick fluorescent specimen and
      were found to be comparable to those usually observed with visible light. For a
      more visual example of the resolution of this instrument, isolated ventricular
      heart muscle cells were loaded with the fluorescent Ca2+ indicator indo 1. This
      allowed us to visualize subcellular structural detail and to illustrate the
      optical sectioning capability of the UV confocal microscope when recording indo 1
      emission. Dual-emission line scans were used to perform ratiometric time-resolved
      detection of Ca2+ transients in voltage-clamped heart muscle cells loaded with
      the salt form of indo 1. The system presented in this paper should significantly
      broaden the range of fluorescent indicators that can be used in confocal
      microscopy.

PMID- 8304427
TI  - Increased intracellular Na+ augments mobilization of Ca2+ from SR in vascular
      smooth muscle cells.
AB  - The effect of a rise in intracellular Na+ concentration ([Na+]cyt) on the amount
      of Ca2+ in intracellular stores was studied in vascular smooth muscle cells from
      the A7r5 line. The relative amount of stored Ca2+ was estimated in fura 2-loaded
      cells by the rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) evoked by Ca2+
      release from the sarcoplasmic reticulum (SR). To improve the detection of
      released Ca2+, extrusion of Ca2+ from the cytosol was minimized by using
      nominally Na+/Ca(2+)-free medium containing 0.5 mM La3+ [for vasoconstrictor
      experiments, the medium contained 0.5 mM ethylene glycol-bis(beta-aminoethyl
      ether)-N,N,N',N'-tetraacetic acid and no La3+]. Ca2+ release was triggered by
      thapsigargin (TG), an SR Ca(2+)-ATPase inhibitor, and by the vasoconstrictors
      arginine vasopressin (AVP) and serotonin (5-HT). Incubation with 1-3 mM ouabain
      for 20 min, which raises [Na+]cyt from 4.4 to 9.0 mM, increased "resting"
      [Ca2+]cyt only slightly (from 87 to 122 nM). However, ouabain greatly augmented
      the release of Ca2+ evoked by TG [from 639 nM (control) to 1,021 nM], by AVP
      (from 993 to 1,597 nM), and by 5-HT (from 559 to 1,486 nM). Ouabain-induced
      augmentation of TG-evoked Ca2+ release was not affected by 10 microM verapamil;
      this implies that the effect of ouabain was not due to Ca2+ entry through voltage
      gated Ca2+ channels. The response to TG was not augmented when ouabain was
      applied for 20 min in Na(+)-free medium (Na+ replaced by equimolar N-methyl-D
      glucamine) to prevent [Na+]cyt from rising.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304428
TI  - Effect of Napip on K0 activation of the Na-K pump in adult rat cardiac myocytes.
AB  - To determine if environmental factors influence the external K (K0) dependence of
      Na-K pump current (Ip), we systematically varied internal (pipette) Na (Napip)
      and Na-K pump activity while measuring the K0 dependence in adult rat cardiac
      myocytes. For each Napip, reactivation of Ip by K0 was dose dependent. The
      maximal Ip (Ipmax) and apparent affinity for K0 binding to the Na-K pump (K0.5)
      increased as Napip increased. The results of making an equimolar substitution of
      tetramethylammonium for K and Cs, and partial Ip inhibition with ouabain, also
      showed that Ipmax and K0.5 increased as Napip increased. We simulated pump
      activity as a function of intracellular Na (Nai) and K0 using a cyclic model of
      the Na-K pump and found that the model predicts K0.5 for K0 binding increases as
      Na increases, even when the conditions are adjusted by removing pipette K and
      partial pump inhibition with ouabain.

PMID- 8304429
TI  - Choline chloride activates time-dependent and time-independent K+ currents in dog
      atrial myocytes.
AB  - Using the whole cell configuration of the patch-clamp technique, we studied the
      effect of isotonic replacement of bath sodium chloride (NaCl) by choline chloride
      (ChCl) in dog atrial myocytes. Our results show that ChCl triggered 1) activation
      of a time-independent background current, characterized by a shift of the holding
      current in the outward direction at potentials positive to the K+ equilibrium
      potential (EK), and 2) activation of a time- and voltage-dependent outward
      current, following depolarizing voltage steps positive to EK. Because the choline
      induced current obtained by depolarizing steps exhibited properties similar to
      the delayed rectifier K+ current (IK), we named it IKCh. The amplitude of IKCh
      was determined by extracellular ChCl concentration, and this current was
      generally undetectable in the absence of ChCl. IKCh was not activated by
      acetylcholine (0.001-1.0 mM) or carbachol (10 microM) and could not be recorded
      in the absence of ChCl or when external NaCl was replaced by sucrose or
      tetramethylammonium chloride. IKCh was inhibited by atropine (0.01-1.0 microM)
      but not by the M1 antagonist pirenzepine (up to 10 microM). This current was
      carried mainly by K+ and was inhibited by CsCl (120 mM, in the pipette) or barium
      (1 mM, in the bath). We conclude that in dog atrial myocytes, ChCl activates a
      background conductance comparable to ACh-dependent K+ current, together with a
      time-dependent K+ current showing properties similar to IK.

PMID- 8304430
TI  - Apically and basolaterally internalized aminoglycosides colocalize in LLC-PK1
      lysosomes and alter cell function.
AB  - Aminoglycosides bind to apical and basolateral (BL) membranes of renal epithelial
      cells. However, little is known regarding differential uptake and intracellular
      processing after internalization across these distinct surface membrane domains.
      To examine these processes independently, LLC-PK1 cells were grown on porous
      filters, which allow selective access to both domains. Apical and BL membrane
      uptakes of gentamicin (0.5 mM), quantified using [3H]gentamicin, were linear from
      2 to 24 h (r = 0.99). The 4-h apical gentamicin uptake was 667 +/- 59 pmol/mg
      protein, the BL 748 +/- 26 pmol/mg protein, and concurrent apical and BL uptake
      1,389 +/- 22 pmol/mg protein. Aminoglycoside uptake, documented using indirect
      immunogold techniques, occurred via the apical and BL endocytic systems and
      colocalized with cationic ferritin. Aminoglycosides internalized via the apical
      (gentamicin) and BL (tobramycin) membrane converged at the lysosomal level.
      Gentamicin incorporated via either domain significantly decreased lysosomal N
      acetylglucosaminidase below control values (P < 0.05). We conclude that, after
      binding, aminoglycosides are internalized equally across apical and BL membranes
      of LLC-PK1 cells via receptor-mediated endocytosis, colocalize within the
      lysosomal compartment, and alter cellular function similarly.

PMID- 8304431
TI  - Characteristics and regulation of a muscarinically activated K current in HSG-PA
      cells.
AB  - Whole cell currents were measured in HSG-PA cells (a proposed model for salivary
      gland duct cells) after muscarinic receptor activation or exposure to known
      signaling agents. Exposure to carbachol or oxotremorine M produced large and
      often oscillatory increases in outward current whose reversal potentials
      indicated a K current. The current was sensitive to extracellular atropine,
      charybdotoxin, and quinine, but not apamin, and to 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid in the pipette. The response was prolonged or
      increased by guanosine 5'-O-(3-thiotriphosphate) and mimicked by D-myo-inositol
      1,4,5-trisphosphate (IP3) or heparin in the pipette and by extracellular Ca
      ionophores. Tetraethylammonium indirectly inhibited the response via the
      muscarinic receptor. Fura 2 in cell suspensions showed that muscarinic agonists
      increased cytosolic Ca ion concentration ([Ca2+]i) five- to sevenfold, and
      measurements with indo 1 in individual cells showed that the oscillatory changes
      in outward current were tightly correlated with parallel changes in [Ca2+]i. The
      results indicate that muscarinic receptor stimulation of HSG-PA cells activates
      Ca(2+)-activated K channels through a signaling pathway involving a G protein,
      IP3 production, and increased [Ca2+]i levels. These findings are similar to those
      in salivary gland acinar cells.

PMID- 8304432
TI  - pH, morphology, and diffusion in lateral intercellular spaces of epithelial cell
      monolayers.
AB  - The lateral intercellular spaces (LIS) of reabsorptive epithelia are the site of
      the proposed local osmotic gradient responsible for transepithelial transport. We
      developed techniques for loading the LIS of living cultured renal cells (MDCK and
      LLC-PK1) with the fluorescent dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein
      (BCECF), visualizing LIS geometry, measuring pH, and determining the BCECF
      diffusion coefficient within the LIS. The LIS pH was remarkably constant and
      differed substantially from that of the superfusate in both the presence and
      absence of HCO3 or CO2. The LIS of MDCK cells had a pH of 7.66 +/- 0.04 in
      bicarbonate-free solutions of pH 7.0, 7.4, or 7.8. In bicarbonate-containing
      solutions, MDCK LIS pH was acidic to the superfusate by 0.3-0.4 units. In the
      absence of bicarbonate, the LIS of LLC-PK1 cells was markedly acidic (6.83 +/-
      0.05), becoming alkaline by approximately 0.25 units in the presence of
      bicarbonate. Gradients in pH or dye concentration were not detected within the
      LIS. The diffusion coefficient of BCECF within the LIS was approximately equal to
      that seen in free solution.

PMID- 8304433
TI  - Acidification of three types of liver endocytic vesicles: similarities and
      differences.
AB  - Endocytosed ligands move through a series of progressively more acidic vesicles.
      These differences in pH (pHi) could reflect differences in ion transport
      mechanisms. Vesicles representing three stages of endocytosis, compartment for
      uncoupling of receptor and ligand (CURL), multivesicular bodies (MVB), and
      receptor recycling compartment (RRC), were studied, and all exhibited ATP
      dependent electrogenic acidification that was a saturable function of medium
      chloride. Initial rates of acidification differed (RRC > CURL > MVB), and proton
      influx was similar for CURL and RRC but slower for MVB. Steady-state ATP
      dependent pHi in the three vesicles was more similar. Vesicle membrane potential
      was substantial (+41 to +69 mV) in low-chloride medium and greatest for RRC but
      was low (-6 to +6 mV) in 140 mM KCl. These vesicles also exhibited -22 to -37 mV
      Donnan potentials. Steady-state pump-generated proton electrochemical gradients
      (delta mu H+) ranged from 114 to 175 mV and were greater for CURL and RRC than
      for MVB; however, delta mu H+ changed little over a 140-fold difference in
      chloride concentration. Proton leak rates were faster in CURL and RRC than in
      MVB, but proton efflux was similar. Finally, proton fluxes and permeabilities,
      calculated with regard to surface area, differed in the opposite direction (MVB >
      CURL > RRC). Thus, for the endocytic vesicles studied, intrinsic differences in
      proton flux and in vesicle geometry could be demonstrated that contributed to
      differences in pre-steady-state vesicle pHi.

PMID- 8304434
TI  - K-Cl cotransport, pH, and role of Mg in volume-clamped low-K sheep erythrocytes:
      three equilibrium states.
AB  - Ouabain-resistant K efflux and Rb influx in Cl and NO3 media were studied in
      volume-clamped low-K (LK) sheep red blood cells (SRBC) with normal and
      experimentally reduced cytoplasmic Mg (Mgi) levels as function of pH and at 37
      degrees C. Sucrose was added to solutions with constant ionic strength and
      variable pH to maintain normal cell volume. Cl-dependent ouabain-resistant K(Rb)
      fluxes (K-Cl cotransport) at unity relative cell volume exhibited a maximum at pH
      approximately 7 in normal-Mgi LK cells consistent with the apparent acid pH
      activation reported for human erythrocytes. However, in LK SRBC with Mgi lowered
      by A-23187 and an external Mg chelator, K(Rb)-Cl cotransport was reversibly
      activated as the pH was raised from 6.5 to 9. The alkaline pH effect on Cl
      dependent Rb influx in low-Mgi LK SRBC was due to a 10-fold rise in the maximum
      velocity values without a major change in the Km values. The pH dependence of the
      experimental flux reversal point, i.e., the extracellular Rb concentration at
      which no net K-Cl cotransport occurs, approximately paralleled that of the flux
      reversal point predicted from the ratio of the ion products, in both control and
      low-Mgi LK cells, albeit with a small displacement to higher extracellular Rb
      concentration at all pH values. The kinetic data can be explained by a general
      minimum three-state equilibrium in which deprotonation recruits transporters from
      a resting R state into the active A state modified by Mgi to an inactive I
      state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304435
TI  - Experimental approaches in muscle metabolism: hindlimb perfusion and isolated
      muscle incubations.
AB  - The perfusion of rat hindlimb muscles and the isolated in vitro muscle
      preparation are usually the preferred methods for investigating muscle
      metabolism. In light of recent concerns about the incubated muscle preparation,
      we have examined the problems, the advantages, and the viability of these two
      experimental techniques, with focus on glucose metabolism. A major advantage of
      the hindlimb perfusion system is that it maintains its metabolic viability very
      well, and perfusions in resting muscles can be achieved successfully with cell
      free media. However, variations in the perfused rat hindlimb procedures result in
      considerable differences in perfusate flow among muscles, making quantitative
      comparisons among perfusion procedures difficult. Metabolic viability has been
      identified as a problem in some isolated in vitro muscle preparations. We have
      provided criteria to avoid muscle hypoxia. Minimum levels of insulin seem to be a
      key requirement to maintaining the muscle's viability, and essential amino acids
      are required to retard an increase in the basal rate of glucose and amino acid
      uptake. Under such conditions metabolic viability can be maintained during
      prolonged incubations (9-30 h). Both the isolated in vitro muscle preparation and
      the hindlimb perfusion preparation are viable models for the study of muscle
      metabolism.

PMID- 8304436
TI  - Endothelial cells stimulate aldosterone release from bovine adrenal zona
      glomerulosa cells.
AB  - Intra-adrenal factors promote basal as well as adrenocorticotropic hormone (ACTH)
      , angiotensin-, and flow-induced steroid secretion. Because endothelial cells
      respond to changes in flow and are in a close anatomical relationship to
      steroidogenic cells, we examined the effect of endothelial cells on the secretion
      of aldosterone from zona glomerulosa (ZG) cells. Endothelial cells and
      endothelial cell-conditioned medium (EC-CM) stimulated the release of aldosterone
      from ZG cells. The stimulatory effect was related to the concentration of
      endothelial cells or EC-CM. The maximal stimulatory effect was 60-70% of the
      maximal effect of ACTH. Endothelial cells alone did not produce aldosterone.
      Human fibroblasts were ineffective in promoting aldosterone release. Endothelial
      cells and EC-CM failed to stimulate cortisol release from zona fasciculata cells.
      Treatment of the EC-CM with trypsin and pronase abolished the activity,
      indicating that a protein mediated the effect. However, the EC-CM activity could
      be distinguished from angiotensin, endothelin-1, and bradykinin. The factor
      stimulated the formation of pregnenolone but not the conversion of corticosterone
      to aldosterone. This endothelium-derived steroidogenic factor appeared to be a
      novel stimulus to aldosterone secretion. This study represents the first
      demonstration that endothelial cells alter endocrine function in vitro.

PMID- 8304437
TI  - Differential glucocorticoid effects on catecholamine responses to stress.
AB  - There have been relatively few studies of the relationships between
      glucocorticoid and catecholamine responses to stress. We have therefore
      determined plasma levels of adrenocorticotropic hormone (ACTH), cortisol (F),
      norepinephrine (NE), and epinephrine (Epi) in four intact sheep treated with
      cortisol, dexamethasone (DM), or saline (S) and subjected to both audiovisual
      (barking dog) and insulin-induced hypoglycemic stress. In control sheep, exposure
      to both stressors resulted in acute rises in ACTH, F, Epi, and NE, with the rises
      after insulin being greater than those after dog stress. Pretreatment with DM
      blocked the ACTH and F responses to stress. Both DM and F markedly attenuated the
      Epi response to hypoglycemia, whereas the rises in NE after each stress and those
      of Epi after dog stress were unaffected by steroid treatment. In a second
      experiment with six sheep treated with S or DM only and subjected to the same
      stressors in reverse order, the same results were obtained, excluding a
      confounding effect of prior stress. We conclude that 1) the poststress release of
      NE, presumably primarily from extra-adrenal sources, is largely steroid
      independent; 2) the mechanism of release of Epi from the adrenal medulla in
      response to audiovisual stress is different from that after hypoglycemia; and 3)
      this may reflect different inputs from central glucocorticoid receptors to
      splanchnic outflow in the two situations.

PMID- 8304438
TI  - Ten days of exercise training reduces glucose production and utilization during
      moderate-intensity exercise.
AB  - We have previously shown that 12 wk of endurance training reduces the rate of
      glucose appearance (Ra) during submaximal exercise (Coggan, A. R., W. M. Kohrt,
      R. J. Spina, D. M. Bier, and J. O. Holloszy. J. Appl. Physiol. 68: 990-996,
      1990). The purpose of the present study was to examine the time course of and
      relationship between training-induced alterations in glucose kinetics and
      endocrine responses during prolonged exercise. Accordingly, seven men were
      studied during 2 h of cycle ergometer exercise at approximately 60% of
      pretraining peak oxygen uptake on three occasions: before, after 10 days, and
      after 12 wk of endurance training. Ra was determined using a primed, continuous
      infusion of [6,6-2H]glucose. Ten days of training reduced mean Ra during exercise
      from 36.9 +/- 3.3 (SE) to 28.5 +/- 3.4 mumol.min-1.kg-1 (P < 0.001). Exercise
      induced changes in insulin, C-peptide, glucagon, norepinephrine, and epinephrine
      were also significantly blunted. After 12 wk of training, Ra during exercise was
      further reduced to 21.5 +/- 3.1 mumol.min-1.kg-1 (P < 0.001 vs. 10 days), but
      hormone concentrations were not significantly different from 10-day values. The
      lower glucose Ra during exercise after short-term (10 days) training is
      accompanied by, and may be due to, altered plasma concentrations of the major
      glucoregulatory hormones. However, other adaptations must be responsible for the
      further reduction in Ra with more prolonged training.

PMID- 8304439
TI  - Advances in kinetic analysis of insulin-stimulated GLUT-4 translocation in
      adipose cells.
AB  - GLUT-4 is the major insulin-sensitive glucose transporter in muscle and adipose
      tissue. Regulation of GLUT-4 is an important component of whole body glucose
      homeostasis. Abnormalities in the regulation of insulin-stimulated reversible
      translocation of glucose transporters have been observed in various pathological
      states, including diabetes. Recently, the development of specific photolabels for
      glucose transporters and the availability of antibodies against the various
      transporter isoforms have presented the opportunity for detailed kinetic analysis
      of GLUT-4 regulation. A kinetic analysis of some of the most recent data is
      presented to demonstrate how this approach can advance the understanding of GLUT
      4 regulation. Some areas in which the currently available data limit the ability
      to resolve certain mechanistic questions are noted. Using a two-compartment
      model, we show that the mechanism of insulin-stimulated GLUT-4 translocation is
      likely to involve a large increase in the exocytosis rate of GLUT-4 with a
      minimal decrease in the endocytosis rate. Mathematical models based on these
      kinetic analyses are helpful for testing hypotheses and designing experiments to
      elucidate the molecular and cellular mechanisms of GLUT-4 regulation under normal
      and pathological conditions. This type of approach may be useful for evaluating
      the contribution of GLUT-4 regulation to the pathogenesis of diabetes.

PMID- 8304440
TI  - Importance of transcapillary insulin transport to dynamics of insulin action
      after intravenous glucose.
AB  - Insulin action in vivo is determined by both transendothelial insulin transport
      (TET) across the capillary and subsequent insulin binding and postreceptor
      events. To examine TET under non-steady-state conditions, we performed
      intravenous glucose tolerance tests (IVGTT; 0.3 g/kg; n = 7) on conscious dogs.
      At basal, insulin in lymph was only 53 +/- 7% of plasma insulin (P < 0.001),
      whereas lymph glucose exceeded plasma levels (109 +/- 4 vs. 104 +/- 4 mg/dl,
      respectively; P < 0.02). On injection, dynamics of glucose in plasma and lymph
      were similar, suggesting rapid equilibration of glucose between compartments. In
      contrast, insulin appearance in lymph was delayed relative to plasma (5.1 +/- 1.3
      vs. 2 +/- 0 min), peaked later (21 +/- 2 vs. 8 +/- 2 min), attained peak value of
      only 52 +/- 6% of plasma insulin (range, 35-76%), and remained lower than plasma
      insulin throughout the IVGTT (P < 0.05 or better). Minimal model-derived insulin
      sensitivity (SI) averaged 3.55 +/- 0.75 x 10(-4) min-1/(microU/ml). There was a
      strong linear relationship between lymph insulin and its effect on glucose
      disappearance [X(t), r = 0.95 +/- 0.01]. Determination of the relative
      contributions of TET and post-TET insulin-sensitive processes to overall SI
      revealed that cellular sensitivity to interstitial insulin dominated (r2 = 0.55),
      but was not the exclusive determinant of, overall SI, as insulin transport was
      also important (r2 = 0.21). TET is a previously unrecognized contributor to SI in
      vivo.

PMID- 8304441
TI  - Low-density lipoprotein receptors in rat adipocytes: regulation with fasting.
AB  - Adipose tissue metabolism is exquisitely sensitive to caloric intake. With
      increasing adiposity more triglyceride and cholesterol are stored within
      increasingly large adipocytes, whereas less triglyceride and cholesterol are
      stored as the size of the fat cell decreases. A portion of the uptake of
      cholesterol by adipocytes is mediated by low-density lipoprotein (LDL) receptors.
      The present studies addressed whether LDL receptors are differentially regulated
      in adipose tissue and the liver during fasting in the rat. Two days of fasting
      caused a reduction in body weight with an approximately 40% decrease in the
      epididymal fat depot and fat cell size. No changes in serum cholesterol were
      noted, but serum triglycerides fell approximately 55% with fasting. LDL receptors
      detected by immunoblotting decreased progressively with fasting to levels that
      were 95% below controls in adipocytes isolated from epididymal fat pads by 2-3
      days. In contrast, hepatic LDL receptor expression was unaltered by fasting.
      After 2 days of fasting, the rate of synthesis of LDL receptors in isolated
      adipose cells was decreased approximately 35%, whereas levels of LDL receptor
      mRNA were diminished approximately 55%. It is concluded that the expression of
      LDL receptors in rat adipocytes is markedly downregulated during fasting through
      transcriptional and posttranscriptional mechanisms. Furthermore, LDL receptor
      expression is differentially regulated in adipose tissue and liver during fasting
      in the rat.

PMID- 8304442
TI  - Phosphate transport by osteoblasts from X-linked hypophosphatemic mice.
AB  - Hypophosphatemic vitamin D-resistant rickets is characterized by impaired renal
      reabsorption of Pi. The underlying mechanism of this abnormality remains unknown.
      Because the osteoblast is likely a target for the HYP mutation, we investigated
      the Pi transport activity in osteoblasts isolated from the murine homologue for
      the human disease, the Hyp mouse. Kinetic analysis of sodium-dependent Pi uptake
      in quiescent normal and Hyp osteoblasts indicated no significant differences in
      apparent maximal capacity (Vmax) and apparent affinity (Km) of the carrier for
      Pi. In rapidly growing cells, higher levels of Pi uptake were observed in mutants
      cells associated with a 1.4- to 1.7-fold increase in Vmax and no change in Km for
      Pi. This increase in Pi uptake seemed related to changes in the sodium
      electrochemical gradient inasmuch as a similar increase was observed in alanine
      uptake. The adaptive response of sodium-dependent Pi transport to Pi deprivation
      was not altered in mutant cells relative to normal cells. To test whether the
      expression of a Pi transport defect was dependent on a humoral factor for its
      expression, we evaluated the activity of the serum from Hyp mice on Pi transport
      in osteoblasts from both genotypes. No difference in activity was observed
      between sera from normal and mutant mice. In summary, cultured osteoblasts
      derived from Hyp mice did not express impaired sodium-dependent Pi transport when
      compared with cells from normal mice.

PMID- 8304443
TI  - Rat Prl and TSH secretion are regulated differently by K(+)-channel blockers.
AB  - All four different K(+)-channel blockers [tetraethylammonium (TEA), a
      nonselective K(+)-channel blocker; tolbutamide, an ATP-sensitive K(+)-channel
      blocker; quinine and 4-aminopyridine, both primarily voltage-dependent K(+)
      channel blockers] stimulated prolactin (Prl) secretion by acutely dispersed
      anterior pituitary cells but had no effect on thyroid-stimulating hormone (TSH)
      secretion. TEA stimulated Prl secretion in a dose-dependent manner between 1
      microM and 20 mM, but even as high as 20 mM, TEA did not induce TSH secretion.
      Valinomycin (2 microM), a K+ ionophore, inhibited both basal and TEA-induced Prl
      secretion. TEA-stimulated Prl secretion was abolished by using a Ca(2+)-depleted
      medium or adding 10 microM dopamine. TEA did not reverse the inhibitory effect of
      dopamine on thyrotropin-releasing hormone-induced Prl secretion. Our data
      indicate that K+ channels may play a role in the secretion of adenohypophysial
      hormones that is idiosyncratic for each hormone. Differences in the role of K+
      channels may reflect differences between the various pituitary cell types in
      plasma membrane ion channel composition, membrane potential, or the mechanism of
      exocytosis.

PMID- 8304444
TI  - Different effects of amiodarone on transport of T4 and T3 into the perfused rat
      liver.
AB  - Uptake and metabolism of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were
      studied in isolated perfused livers of control and amiodarone-treated rats (40
      mg.kg body wt-1.day-1, 22 days). With the use of this perfusion system and a two
      pool model describing thyroid hormone kinetics, total uptake was evaluated by the
      half-time (t1/2) of the fast component of the biphasic thyroid hormone
      disappearance from the medium and by the fractional influx rate constant (k21).
      Metabolism was assessed by the t1/2 of the slow component, by determination of
      breakdown products in medium and bile, and by thyroid hormone disposal according
      to the two-pool model. Disposal was corrected for differences in mass transfer
      into the metabolizing pool. In amiodarone-treated rats, both uptake and
      metabolism of T4 were decreased. Furthermore, it was shown that only transport
      into the metabolizing liver compartment and not uptake into the nonmetabolizing
      liver compartment was decreased. Both uptake and total metabolism of T3 were
      unaffected by amiodarone. The results showed that the different transport systems
      for T4 and T3 described in isolated rat hepatocytes may also be operative in the
      intact rat liver. Furthermore, it can be concluded that the low-T3 syndrome,
      caused by treatment with amiodarone, may be due to both impaired transport and
      impaired 5'-deiodination.

PMID- 8304445
TI  - Prostaglandin F2 alpha releases calcium from a thapsigargin-sensitive pool in
      ovine large luteal cells.
AB  - Thapsigargin (TG) and A23187 were used to examine the regulation of cytosolic
      free calcium (Cai2+) in ovine large and small luteal cells. Thapsigargin (50 nM)
      induced a sustained increase of Cai2+ in fura 2-acetoxymethyl ester (AM)-loaded
      cells (large = 1.32 +/- 0.07-fold, small = 1.45 +/- 0.07-fold, P < 0.05). A23187
      (1 microM) induced a rapid transient increase of Cai2+ (large = 1.37 +/- 0.07
      fold, small = 1.46 +/- 0.10-fold, P < 0.05). In large cells, 0.5 microM
      prostaglandin F2 alpha (PGF2 alpha) increased Cai2+ 1.54 +/- 0.11-fold.
      Pretreatment with 50 nM TG abolished the PGF2 alpha-induced calcium response.
      Pretreatment with PGF2 alpha attenuated (P < 0.05) the TG-induced Cai2+ increase.
      Progesterone secretion was significantly (P < 0.05) inhibited by incubation with
      50 nM TG, 1 microM A23187, and 0.5 microM PGF2 alpha in large but not small
      cells. These data suggest that PGF2 alpha releases calcium from a TG-sensitive
      intracellular calcium pool in ovine large luteal cells.

PMID- 8304446
TI  - Amino acid uptake by the fetal ovine hindlimb under normal and euglycemic
      hyperinsulinemic states.
AB  - As part of an effort to establish the contribution of different fetal organs to
      fetal amino acid metabolism, we measured in nine sheep fetuses the uptake of 27
      amino acids by the hindlimb under normal conditions and conditions by euglycemic
      hyperinsulinemia. The fetal hindlimb is representative of nonvisceral tissues,
      which in the mature fetus account for approximately 70% of fetal weight and 30%
      of fetal O2 consumption. In the normal condition, there was a significant uptake
      of 21 amino acids for a net total nitrogen uptake of 132 +/- 21 mg N.day-1 x 100
      g-1. The amino acids taken up by the fetal limb included alanine and glutamine.
      In addition, the fetal limb had significant glutamate and serine uptakes. Because
      glutamate flows from fetus to placenta and there is no fetal uptake of maternal
      serine, this indicates production and interorgan transport of these amino acids
      within the fetus. Insulin infusion significantly decreased the arterial
      concentration of every amino acid with the exception of cystathionine and
      significantly increased limb blood flow and glucose uptake. It significantly
      increased the limb uptake of alanine, asparagine, glycine, isoleucine,
      methionine, and tyrosine, decreased the uptake of aspartate, and produced no
      significant change in the net total nitrogen uptake, which remained similar to
      control (137 +/- 16 mg N.day-1 x 100 g-1).

PMID- 8304447
TI  - In vivo regulation of rat muscle glycogen resynthesis after intense exercise.
AB  - Time courses of the glycogen synthesis rate and of the glucose 6-phosphate (G-6
      P) concentration after an electrically induced exercise were followed in the
      anesthetized rat gastrocnemius by in vivo 13C and 31P nuclear magnetic resonance
      (NMR) spectroscopy, respectively. The ratio of glycogen synthase I to glycogen
      synthase I and D (I/I+D) and allosteric activation by G-6-P were also studied in
      vitro on muscles sampled at rest and 10 min (early recovery) and 100 min (late
      recovery) after exercise. From early recovery to late recovery, the in vivo
      glycogen synthesis rate dropped from 0.46 +/- 0.06 to 0.11 +/- 0.04 mmol.kg wet
      tissue-1.min-1, the G-6-P concentration from 0.83 +/- 0.08 to 0.32 +/- 0.05
      mmol/kg wet tissue, and I/I+D from 83 +/- 4 to 47 +/- 1%. The combination of the
      changes in G-6-P concentration and in I/I+D quantitatively describes the fourfold
      decrease in glycogen synthesis rate from early to late recovery. These results
      demonstrate that phosphorylation, determining glycogen synthase I/I+D, and
      allosteric control of glycogen synthase by G-6-P contribute approximately equally
      to the regulation of the postexercise in vivo glycogen synthesis rate.

PMID- 8304448
TI  - Pre- and posttranslational upregulation of muscle-specific glycogen synthase in
      athletes.
AB  - Expression of muscle-specific glycogen synthase (GS) and phosphofructokinase
      (PFK) was analyzed in seven athletes and eight control subjects who were
      characterized using the euglycemic, hyperinsulinemic (2 mU.kg-1.min-1) clamp
      technique in combination with indirect calorimetry and biopsy sampling of vastus
      lateralis muscle. In the basal state, total GS activity and half-maximal GS
      activation by glucose 6-phosphate (G-6-P) were respectively 34% (P < 0.03) and
      50% (P < 0.005) higher in athletes than in control subjects. In parallel, GS
      mRNA/microgram total RNA in athletes was 40% (P < 0.005) higher. No difference in
      GS immunoreactive protein abundance was found between the groups. PFK activity
      and protein levels were respectively 15% (P < 0.05) and 20% (P < 0.02) lower in
      athletes, whereas no differences was found in the level of PFK mRNA. After 4 h of
      hyperinsulinemia, total glucose disposal rate (P < 0.005) and both nonoxidative
      (P < 0.02) and oxidative (P < 0.03) glucose metabolism were significantly higher
      in athletes. In parallel, after hyperinsulinemia, the relative activation of GS
      by G-6-P was significantly higher in athletes, whereas total activity and gene
      expression of both GS and PFK were unaffected by insulin. We conclude that
      athletes have increased whole body insulin-stimulated nonoxidative glucose
      metabolism associated with both pretranslational (mRNA) and posttranslational
      (enzyme activity) upregulation of GS. However, the immunoreactive mass of GS is
      normal, emphasizing that posttranslational regulation of the GS protein activity
      is important for the increased glycogen synthesis rate of muscle in endurance
      trained individuals.

PMID- 8304449
TI  - Low molecular weight GTP-binding proteins: molecular switches regulating diverse
      cellular functions.
AB  - Low molecular weight GTP-binding proteins (LMWG proteins) form a family of
      proteins that shows homology with Ras, are 18-30 kDa in mass, and bind and
      hydrolyze GTP. They act as molecular switches, being active when binding GTP.
      Their activity is regulated by other proteins that influence the dissociation of
      GDP and the rate of GTP hydrolysis. Roles are emerging for these proteins in
      regulation of membrane fusion and cytoskeletal organization and growth. In the
      gastrointestinal tract, the best studied physiological processes that may be
      regulated by LMWG proteins are digestive enzyme and gastric acid secretion.

PMID- 8304450
TI  - Endocrine and amino acid regulation of liver macroautophagy and proteolytic
      function.
AB  - Regulation of liver macroautophagy and protein degradation by hormones and direct
      regulatory amino acids were studied in male 2-mo-old Sprague-Dawley albino rats
      with the use of the antilipolytic agent 3,5'-dimethylpyrazole (DMP; 12 mg/kg body
      wt ip) as a stimulatory agent. Injection of DMP decreased glutamine plasma levels
      and glutamine release from the perfused liver. Autophagic vacuoles were observed
      in the pericanalicular area of liver cells after 30 min. Levels and release of
      other regulatory amino acids did not exhibit any significant decrease but
      subsequently increased. Intraperitoneal administration of glutamine inhibited the
      proteolytic response. In conclusion, these studies demonstrate that in vivo
      induction and control of liver macroautophagy and protein degradation by the
      physiological mechanism (i.e., by shortage of nutrients) involve unbalanced and
      asynchronous changes in the levels of selected direct regulatory amino acids
      (i.e., a decrease in glutamine and a subsequent increase in leucine and tyrosine
      levels).

PMID- 8304451
TI  - Role of nitric oxide in esophageal peristalsis.
AB  - In vitro studies have suggested that NO may be a nonadrenergic, noncholinergic
      inhibitory mediator in the esophageal body. We examined the role of NO in
      physiological peristalsis in anesthetized opossums by assessing the effect of the
      NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on
      esophageal contractions induced by swallows, prolonged vagal efferent nerve
      stimulation, and midesophageal balloon distension. A perfused manometry system
      measured intraluminal pressures 1 and 5 cm orad to the lower esophagus, and
      suction electrodes monitored membrane potential changes at the same locations. NO
      synthase inhibition 1) decreased swallow-induced contraction amplitude in the
      distal esophagus and, when combined with atropine, abolished these contractions;
      2) diminished swallow-induced contraction latencies, predominantly in the distal
      esophagus, thereby decreasing the latency gradient and increasing the peristaltic
      velocity; 3) abolished vagal-stimulation-induced, end-of-stimulus "B"
      contractions and either unmasked or increased the amplitude of intrastimulus "A"
      contractions; 4) abolished the contractions occurring at the end of balloon
      distension; and 5) inhibited the membrane hyperpolarization and the subsequent
      nonadrenergic, noncholinergic depolarization induced by all three stimuli. These
      data support the hypothesis that NO is a mediator of nonadrenergic,
      noncholinergic neurotransmission in the opossum esophagus. Furthermore, the data
      suggest that esophageal peristalsis is mediated by a "blended" activation of
      cholinergic and nonadrenergic, noncholinergic (via NO) neurons.

PMID- 8304452
TI  - Effects of the inflammatory mediator prostaglandin D2 on submucosal neurons and
      secretion in guinea pig colon.
AB  - Conventional flux chamber and intracellular recording methods were used to
      investigate the mode of action of prostaglandin D2 (PGD2) on ion transport in
      muscle-stripped segments of guinea pig colon and on colonic submucosal ganglion
      cells. Application of PGD2 resulted in a dose-dependent increase in short-circuit
      current that was reduced by serosal addition of bumetanide, tetrodotoxin,
      atropine, or piroxicam, but not hexamethonium. Application of PGD2 to submucosal
      neurons evoked a depolarization of the membrane potential that was associated
      with an enhanced spike discharge. In AH/type 2 neurons, postspike
      afterhyperpolarizations were reduced in amplitude and duration. The depolarizing
      responses to PGD2 were not affected by tetrodotoxin, indicative of a direct
      effect of PGD2 on the impaled neurons. Whereas fast excitatory postsynaptic
      potentials (EPSPs) were not affected by PGD2, slow EPSPs were reduced by a
      presynaptic effect, indicating presynaptic suppression of noncholinergic
      neurotransmitter release. The study demonstrates that PGD2 acts as a
      neuromodulator to evoke nerve-mediated chloride secretion, predominantly through
      activation of cholinergic submucosal neurons. The results further indicate that
      PGD2 released from lamina propria immune cells during antigenic stimulation may
      influence mucosal function by altering electrical behavior of submucosal neurons.

PMID- 8304453
TI  - Regenerative potential of abdominal vagal nerves in rats.
AB  - After truncal vagotomy, impaired gastric emptying may represent a serious
      complication. This led us to study the feasibility of a reinnervation of the
      antrum by microsurgical vagorrhaphy and vagoplasty. Sixty-four rats were randomly
      assigned to undergo either 1) no operation (control), 2) laparotomy and vagal
      dissection (sham operation), 3) truncal abdominal vagotomy with nerve segment
      resection, 4) truncal vagotomy followed by vagorrhaphy, or 5) vagal resection
      extending to the nerve of Latarjet followed by grafting of the gap using the
      resected vagal segment (vagoplasty). Six months after surgery, vagal regeneration
      was assessed by morphometry of the anterior vagus and the antral wall and by
      recording the gastric emptying of a radiolabeled meal, the contractile response
      to electrical stimulation of the cervical vagi, and basal and insulin-stimulated
      acid secretion. After truncal vagotomy, there was a marked degeneration of vagal
      fibers and no evidence of spontaneous reinnervation. After vagorrhaphy, a
      recovery of gastric secretory and motor functions as well as morphological data
      indicated vagal regeneration. After vagoplasty, a partial recovery of gastric
      motor functions and the morphological appearance suggested a partial vagal
      reinnervation.

PMID- 8304454
TI  - Identification and characterization of the esophagoglottal closure reflex in a
      feline model.
AB  - To identify a suitable animal model and to delineate the neural pathway and
      target organs of the esophagoglottal closure reflex we studied three species.
      Study showed the existence of an esophagoglottal closure reflex in cats. The
      presence of this reflex could not be documented in the opossum. In monkeys,
      because of the inadequacy of the available recording devices, its presence could
      not be ascertained. In the feline model, the closure response of the vocal folds
      to the abrupt generalized and segmental distension of the esophagus was similar
      to that of the humans. Study findings indicate that among glottal adductor
      muscles at least interarytenoid and lateral cricoarytenoid muscles are involved
      as target organs of the esophagoglottal closure reflex. Decerebration did not
      change the frequency of glottal closure response to esophageal distension,
      supporting the notion that this reflex is completely under brain stem control.
      Bilateral cervical vagotomy abolished the glottal closure induced by esophageal
      distension indicating that this reflex is mediated by the vagus nerve. Upper
      esophageal sphincter (UES) pressure response to esophageal distension by air was
      variable, suggesting that glottal and UES response to esophageal distension,
      although closely coordinated, are not dependent on one another. In summary, an
      esophagoglottal closure reflex exists in feline species, and many similarities in
      the elicitation and mediation of this reflex have been found with that of humans.
      This model could be used for further physiological studies.

PMID- 8304455
TI  - Mechanism of riboflavine uptake by Caco-2 human intestinal epithelial cells.
AB  - The cellular and molecular regulation of intestinal absorption of the water
      soluble vitamin riboflavine (RF) is poorly understood. The availability of a
      suitable in vitro cultured system that possesses the transport characteristics of
      the native intestinal absorptive cells would provide a powerful means to address
      this issue. In this study, we examined RF uptake by the human-derived cultured
      Caco-2 intestinal epithelial cells. RF uptake was Na+ and pH independent and
      occurred without metabolic alterations of the transported RF. Initial rate of RF
      uptake was temperature dependent and saturable as a function of concentration at
      37 degrees C but not at 4 degrees C (apparent Michaelis constant = 0.30 +/- 0.03
      microM, maximal velocity = 209.90 +/- 24.40 pmol.mg protein-1.3 min-1). Unlabeled
      RF, lumiflavine, 8-amino-riboflavine, isoriboflavine, and lumichrome in the
      incubation solution caused significant inhibition of RF uptake. RF uptake was
      also energy dependent and was sensitive to the inhibitory effect of sulfhydryl
      group reagents. The membrane transport inhibitor amiloride, but not 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid, 4-acetamide-4'-isothiocyanostilbene
      2,2'-disulfonic acid, furosemide, or probenecid, inhibited RF uptake in a
      competitive (inhibitory constant = 0.48 mM) and reversible manner. Growing Caco-2
      monolayers in a RF-deficient and oversupplemented media caused significant up-
      and downregulation of RF uptake, respectively. These results demonstrate the
      existence of a carrier-mediated system for RF uptake by Caco-2 cells and provide
      new information regarding amiloride sensitivity, involvement of sulfhydryl
      groups, and up- and downregulation by the substrate level and clarify the
      controversy regarding the role of Na+ in the uptake process.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8304456
TI  - Role of nitric oxide-related inhibition in intestinal function: relation to
      vasoactive intestinal polypeptide.
AB  - This study examined the role of nitric oxide (NO) in tonic inhibition of motor
      activity in isolated, perfused canine ileal segments. Brief addition of N omega
      nitro-L-arginine methyl ester (L-NAME) to the perfusate caused, after a delay, a
      concentration-dependent persistent increase in tonic and phasic activity of
      circular muscle. This increased motor activity was prevented or reversed by
      addition of L- but not D-arginine to the perfusate. Removal of Ca2+ or addition
      of 10(-7) M omega-conotoxin (GVIA) to the perfusate markedly reduced this
      response. The motor activity induced by L-NAME was accompanied by loss of distal
      inhibition and enhanced excitation to low-frequency field stimulation. L-NAME
      infusion significantly reduced tonic vasoactive intestinal polypeptide (VIP)
      output, sodium nitroprusside increased VIP output, but L-arginine infusion did
      not restore VIP output. Atropine (10(-7) M) and/or hexamethonium (10(-4) M)
      reduced the motor response to L-NAME by 75%. Atropine reduced and hexamethonium
      nearly abolished VIP output. We conclude that there is tonic Ca(2+)-dependent NO
      output from perfused intestinal segments dependent on nerves with N-Ca channels,
      that NO acts to inhibit muscle directly and by inhibiting release of excitatory
      mediators, and that this output is the primary inhibitory determinant of
      contractile activity.

PMID- 8304457
TI  - Polymorphonuclear leukocyte infiltration into gastric mucosa after ischemia
      reperfusion.
AB  - Polymorphonuclear leukocytes (PMN) have been implicated in the pathogenesis of
      ischemia-reperfusion injury. The objective of this study was to investigate PMN
      infiltration and distribution within the gastric mucosa of rats subjected to 30
      min gastric ischemia followed by reperfusion. Sections of mucosa were stained for
      PMN using an immunoperoxidase technique, and injury was assessed by quantitative
      histology. In control animals, there were 4 +/- 2 PMN/mm2 in the superficial and
      9 +/- 4 PMN/mm2 in the deep mucosa. This increased significantly to 67 +/- 9
      PMN/mm2 (P < 0.05) and 160 +/- 53 PMN/mm2 (P < 0.01) respectively at 15 min of
      reperfusion. The percentage of these PMN which were extravasated was 83 +/- 4% in
      the superficial mucosa and 82 +/- 4% in the deep mucosa (P < 0.001 compared with
      control levels of 0% in superficial and 10% in deep mucosa). Significant PMN
      infiltration occurred before full expression of mucosal injury and treatment of
      rats with anti-PMN antisera blocked reperfusion injury (treated 10.7 +/- 1.4%
      mucosa damaged, controls 33.5 +/- 2.4%; P < 0.001). Treatment with allopurinol
      (100 mg/kg) significantly reduced the number of infiltrating PMN (superficial 7
      +/- 1/mm2, deep 16 +/- 2/mm2; P < 0.01) and the percentage of extravasating PMN
      (superficial 40 +/- 10%, deep 30 +/- 15%; P < 0.01) while also significantly
      reducing tissue injury (21.9 +/- 1.9% mucosa damaged, P < 0.01 compared with
      controls). We conclude that the immunoperoxidase staining provides a simple means
      of identifying PMN in histological sections. Furthermore, our results support a
      role for PMN in gastric ischemia-reperfusion injury.

PMID- 8304458
TI  - Histamine is not involved in pentagastrin-induced gastric mucosal vasodilation in
      the rat.
AB  - The effects of histamine and its role in the gastric mucosal vascular response to
      pentagastrin were studied in anesthetized rats. Blood flow was measured with
      laser-Doppler flowmetry (LDF) and with red blood cell velocity measurements in
      the superficial mucosal microcirculation. Acid secretion was determined by
      titration of the saline covering 0.8 cm2 of the fundic mucosa. Pentagastrin (40
      micrograms.kg-1 x h-1 i.v. induced a blood flow increase (+40%), which was not
      significantly altered by ranitidine (H2-receptor antagonist, 2 mg/kg iv bolus),
      whereas the stimulated acid output was abolished. In experiments in which the H1
      receptor antagonist pyrilamine (2.5 mg/kg i.v. bolus) was administered before
      pentagastrin stimulation, pentagastrin still increased blood flow by
      approximately 60%. Intravenous histamine (4 mg.kg-1 x h-1) induced a blood flow
      reduction in parallel with the reduction in blood pressure (vascular resistance
      unchanged). Even during intra-arterial (thoracic aorta) infusion of histamine (1
      or 4 mg.kg-1 x h-1), gastric vascular resistance was unchanged. In animals
      pretreated with pyrilamine, histamine (4 mg.kg-1 x h-1 i.v.) left the gastric
      blood flow and blood pressure unchanged. These results indicate that the
      pentagastrin-induced increase in the rat gastric blood flow is not dependent on
      histamine.

PMID- 8304459
TI  - Pancreas growth, tyrosine kinase, PtdIns 3-kinase, and PLD involve high-affinity
      CCK-receptor occupation.
AB  - Cholecystokinin (CCK), CCK octapeptide (CCK-8), and caerulein (Cae) are the most
      potent trophic factors in the pancreas when given exogenously or released from
      the intestine. Recent studies have suggested that this growth-promoting effect of
      CCK was initiated through the occupation of the CCKA receptor. This study was
      then undertaken to determine whether occupation of the high- or low-affinity CCKA
      receptor is involved in the growth process and to establish which transduction
      signals have been selectively activated. As an answer to the first question, rats
      were infused with CCK JMV-180, a CCKA high-affinity agonist, at doses of 50, 100,
      150, and 300 micrograms.kg-1.h-1, or Cae (0.25 micrograms.kg-1.h-1) for 4 days.
      After rats were killed, their pancreatic weight and contents of protein, DNA,
      RNA, amylase, and chymotrypsinogen were estimated. To investigate the
      transduction signals, rats were infused for 30 min to 4 h with 300 micrograms.kg
      1.h-1 JMV-180, or pancreatic acini were exposed in vitro to 1 microM JMV-180 for
      5 or 30 min. After rats were killed, pancreases were used to monitor tyrosine
      kinase, phosphatidylinositol (PtdIns) 3-kinase, and phospholipase D (PLD)
      activities. The first set of experiments indicates that JMV-180 caused a dose
      dependent effect on pancreas growth, with the 300 micrograms.kg-1 x h-1 dose
      giving the maximal effect comparable to that of Cae. Furthermore, JMV-180 induced
      concomitant early increases in tyrosine kinase and PLD activities both in vivo
      and in vitro and PtdIns 3-kinase in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304460
TI  - Aldosterone-induced apical Na+ and K+ conductances are located predominantly in
      surface cells in rat distal colon.
AB  - Aldosterone is a major regulator of Na(+)-absorptive and K(+)-secretory processes
      in the distal segment of mammalian colon. In this study, the distribution of
      aldosterone-sensitive cell types in isolated rat distal colon was determined
      using site-directed intracellular microelectrodes, specific Na(+)- and K(+)
      channel blockers, and aldosterone-receptor binding techniques.
      Electrophysiological data indicated that aldosterone induced parallel apical
      membrane Na+ and K+ conductances, mainly in surface cells and to a significantly
      lesser degree in crypt cells. Scatchard analyses of aldosterone-receptor binding
      in cytosolic fractions revealed the maximum number of specific binding sites in
      whole mucosal homogenate and in the upper one-third and lower two-thirds of
      isolated crypt units to be 74.9 +/- 2.0, 59.8 +/- 2.4, and 59.3 +/- 3.2 fmol/mg
      protein, respectively, indicating the presence of aldosterone receptors in the
      crypt cell population. We conclude that in rat distal colon aldosterone-induced
      Na+ and K+ conductances (and by inference, electrogenic Na(+)-absorptive and K(+)
      secretory processes) are located predominantly in the surface cell population and
      to a lesser extent in crypt cells, which also contain aldosterone receptors. This
      spectrum of aldosterone-induced Na+ and K+ conductances may reflect varying
      stages of differentiation along the surface cell-crypt cell axis.

PMID- 8304461
TI  - Temporal pattern of rat small intestinal gene expression with refeeding.
AB  - Studies were carried out to elucidate the molecular mechanisms underlying small
      intestinal epithelial growth. Adult rats were fasted for 4 days and then refed a
      chow diet for up to 48 h. Histological examination confirmed the sequential
      occurrence of mucosal atrophy and hyperplasia. Northern blot analyses of RNA
      derived from small intestinal mucosal scrapings revealed a striking pattern of
      alterations in the expression of two different categories of genes. There were
      very early increases in the expression of c-fos and c-jun, reflecting the
      mitogenic response to refeeding that occurs within the crypt compartment. Studies
      using the protein synthesis inhibitor cycloheximide suggest that c-fos and c-jun
      are part of the "immediate-early" response of the small intestine. At later time
      points after the refeeding stimulus, differential changes occurred in the
      expression of the brush-border enzymes, lactase, and intestinal alkaline
      phosphatase (IAP). Refeeding caused a decrease in lactase gene expression and an
      increase in the expression of the 3.0-kb IAP mRNA species, reflecting a return of
      the villus phenotype to the normal fed state. Thus we have demonstrated a complex
      and temporally related pattern of gene expression within the small intestinal
      epithelium upon refeeding. The results provide insight into the relationship
      between the processes of intestinal growth and differentiation.

PMID- 8304462
TI  - Serosal and cutaneous recordings of gastric myoelectrical activity in patients
      with gastroparesis.
AB  - The aims of this study were to 1) investigate gastric myoelectrical activity in
      patients with gastroparesis, 2) validate the cutaneous electrogastrogram (EGG) in
      tracking the frequency change of the gastric slow wave, and 3) investigate the
      effect of electrical stimulation on gastric myoelectrical activity. Gastric
      myoelectrical activity was recorded in 12 patients with documented gastroparesis
      using serosal electrodes for > 200 min in each subject. All recordings were made
      at least 4 days after surgery. Each session consisted of a 30-min recording in
      the fasting state and a 30-min recording after a test meal. The test meal (liquid
      or mixed) was selected according to patient's tolerance. Electrical stimulation
      was performed in three subjects via the serosal electrodes at a frequency of 3
      cycles/min. Gastric myoelectrical activity was recorded using serosal electrodes
      in each session. The serosal recording showed slow waves of 2.5 to 4.0 cycles/min
      in all 12 subjects. Absence of spikes was noted in 11 of the 12 subjects. The
      simultaneous serosal and cutaneous recording of gastric myoelectrical activity
      showed that the frequency of the EGG was exactly the same as that of the serosal
      recording. Liquid meals resulted in a significant decrease in slow-wave frequency
      (Student's t test, P = 0.006), and the EGG accurately reflected this change.
      Electrical stimulation had no effect on the frequency of the gastric slow wave
      and did not induce spikes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304463
TI  - Glycogenolytic effect of adenosine involves ATP from hepatocytes and eicosanoids
      from Kupffer cells.
AB  - In the perfused liver, infusion of adenosine (50 microM) caused an increase in
      portal pressure and glucose output as well as a brief increase in oxygen uptake
      followed by a transient decrease within 1 min. Half-maximal glycogenolytic effect
      was observed with approximately 20 microM adenosine, and the stimulation was
      maximal at concentrations > 50 microM. The effect of adenosine was blocked when
      Kupffer cells were destroyed with gadolinium chloride treatment (10 mg/kg iv),
      supporting the hypothesis that eicosanoid release from Kupffer cells participates
      in the effect of adenosine in the liver. Although adenosine has been reported to
      increase eicosanoid release from perfused liver (S. vom Dahl, M. Wettstein, W.
      Gerok, and D. Hussinger, Biochem. J. 270: 39-44, 1990), in this study adenosine
      failed to stimulate prostaglandin release from cultured Kupffer cells at
      concentrations ranging from 1 microM to 1 mM, casting doubt on the hypothesis
      that Kupffer cells are totally responsible for the effect of adenosine. In
      contrast, adenosine increased ATP transiently from 4 to 15 nM in effluent from
      perfused livers concomitant with a transient increase in carbohydrate output and
      portal pressure. To assess which type of hepatic cells released ATP after
      addition of adenosine, parenchymal, Kupffer, and endothelial cells were isolated
      and incubated with adenosine. Adenosine increased ATP concentrations in culture
      media of parenchymal cells but not from Kupffer or endothelial cells.
      Furthermore, ATP stimulated prostaglandin release from cultured Kupffer cells,
      whereas ATP (10 microM) infusion caused glucose release with kinetics similar to
      adenosine in perfused livers, an effect that was blocked by destroying Kupffer
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304464
TI  - Comments on "Mucins: structure, function, and role in pulmonary disease".

PMID- 8304465
TI  - Growth factors alter neonatal type II alveolar epithelial cell proliferation.
AB  - The type II alveolar epithelial cell plays a critical role in the repair of lung
      injury by repopulating the entire damaged alveolar epithelium. We report our
      studies of the effects of known growth factors on the in vitro proliferation of
      isolated neonatal rabbit type II cells. Transforming growth factor-alpha (TGF
      alpha) and epidermal growth factor (EGF) increased [3H]thymidine incorporation,
      cell number, and labeling index above control. Transforming growth factor-beta
      (TGF-beta) decreased [3H]thymidine incorporation, cell number, and labeling index
      compared with control. When added simultaneously, TGF-beta blocked the
      stimulatory effect of TGF-alpha or EGF. If TGF-alpha is added before TGF-beta,
      the ability of TGF-beta to block the mitogenic effect of TGF-alpha was diminished
      the later in time TGF-beta was added. If TGF-beta was added first, later addition
      of TGF-alpha had no effect. The current work demonstrates that specific growth
      factors, including some known to be produced by other lung cells, alter the
      proliferation in vitro of isolated neonatal rabbit type II alveolar epithelial
      cells.

PMID- 8304466
TI  - Interleukin-1-induced lung neutrophil accumulation and oxygen metabolite-mediated
      lung leak in rats.
AB  - We found that intratracheal administration of recombinant interleukin-1 alpha (IL
      1) into rats rapidly (< 5 h) increased neutrophils in lung lavages and caused an
      acute edematous lung injury which was reflected by lung albumin accumulation
      (lung leak) and histological abnormalities (perivascular cuffing). These IL-1
      dependent processes were inhibited by prior administration of recombinant IL-1
      receptor antagonist and did not occur following administration of heated IL-1.
      Several lines of evidence suggested that neutrophil-derived oxygen metabolites
      contributed to lung leak. First, lung leak did not occur in rats rendered
      neutropenic by vinblastine treatment 4 days before IL-1 administration but did
      occur in neutrophil-replete rats given vinblastine 1 day before IL-1
      administration and control rats given IL-1. Second, treatment with a hydroxyl
      radical scavenger, dimethyl sulfoxide (DMSO) or a superoxide anion scavenger,
      manganese superoxide dismutase, decreased lung leak, lung lavage neutrophils, and
      histological abnormalities in rats given IL-1 intratracheally. Third,
      intratracheal IL-1 administration increased lung oxidized glutathione (GSSG)
      levels and expired H2O2 concentrations, and these two indices of oxidative stress
      were decreased by dimethyl sulfoxide or manganese superoxide dismutase treatment.
      We conclude that intratracheal administration of IL-1 increases neutrophils in
      the lung and causes a neutrophil and oxygen metabolite-dependent acute edematous
      lung injury.

PMID- 8304467
TI  - Upregulation of sodium conductive pathways in alveolar type II cells in sublethal
      hyperoxia.
AB  - We investigated whether exposure of rats to sublethal hyperoxia (85% O2 for 7
      days) raises the levels of proteins antigenically related to Na+ channels in
      alveolar type II (ATII) cells and, if so, whether this rise was accompanied by an
      increase in conductive Na+ transport in vitro. ATII cells were isolated from the
      lungs of these rats at the end of the exposure period. In Western blot studies, a
      polyclonal antibody raised against Na+ channel protein (NaAb), recognized in a
      specific manner a 135 +/- 10 kDa polypeptide in plasma membrane vesicles of ATII
      cells from both control and oxygen-exposed rats. However, higher levels of
      immunoreactivity were seen in ATII cells from oxygen-exposed rats. When ATII
      cells were patched in the whole cell mode using symmetrical solutions (150 mM
      Na(+)-glutamate), outward rectified Na+ currents were observed. When corrected
      for cell capacitance, both inward and outward currents of ATII cells from rats
      exposed to hyperoxia were significantly higher than control. Addition of either 1
      microM amiloride or 1 microM 5-(N-ethyl-N-isopropyl)-2'-4'-amiloride in the bath
      solution decreased the magnitude of outward currents of both control and
      hyperoxic ATII cells by approximately 50%. Taken together, these results indicate
      that exposure of rats to sublethal hyperoxia results in upregulation of ATII cell
      conductive pathways with low affinity to amiloride and increased Na+ transport.
      This may be an early adaptive response that limits the degree of alveolar edema
      in injured lungs.

PMID- 8304468
TI  - Protection against oxygen toxicity by tracheal insufflation of endotoxin: role of
      Mn SOD and alveolar macrophages.
AB  - Endotoxin and the cytokines, tumor necrosis factor and interleukin-1, are known
      to protect adult rats against O2 toxicity. However, whether the effect of
      endotoxin is mediated through its direct effect on lung cells or through
      cytokines is not clear. In this study, we demonstrated that endotoxin at a dosage
      of 5 micrograms/rat (14-20 micrograms/kg) attenuated O2-induced pulmonary injury
      and markedly prolonged the survival of rats exposed to 100% O2. Endotoxin was
      more protective when given by intratracheal insufflation or intravenous injection
      than by intraperitoneal injection. The endotoxin-induced O2 tolerance was
      associated with a selective enhancement of pulmonary manganese superoxide
      dismutase, but not Cu,Zn SOD, mRNA. In addition, depletion of 84% rat alveolar
      macrophages by liposome-encapsulated dichloromethylene diphosphonate, resulted in
      a marked reduction (86%) of endotoxin-induced release of tumor necrosis factor
      into the alveolar space. However, endotoxin was still protective in these
      alveolar macrophage-depleted animals.

PMID- 8304469
TI  - Serotonin produces both hyperplasia and hypertrophy of bovine pulmonary artery
      smooth muscle cells in culture.
AB  - Serotonin [5-hydroxytryptamine (5-HT)] has a dual effect on bovine pulmonary
      artery smooth muscle cells (SMC) in culture (S.-L. Lee, W. W. Wang, B. J. Moore,
      and B. L. Fanburg. Circ. Res. 68: 1362-1368, 1991.). Cellular internalization of
      5-HT stimulates DNA synthesis and cellular proliferation, whereas the action of 5
      HT on a cell surface receptor elevates adenosine 3',5'-cyclic monophosphate and
      inhibits proliferation. The present study shows that 5-HT causes proliferation of
      both pulmonary artery and aortic SMC but not of endothelial cells or fibroblasts.
      Furthermore, c-myc and alpha- and beta-actin gene expressions of pulmonary artery
      SMC were elevated after 2-h incubation with 5-HT, before stimulation of
      [3H]thymidine incorporation. Actinomycin D (0.05 micrograms/ml) but not
      cycloheximide (1 microgram/ml) inhibited the gene expression produced by 5-HT.
      Growth-arrested SMC progressed from a G0 quiescent state through a normal cell
      cycle when subjected to 5-HT, 5-HT plus 25 ng/ml insulin-like growth factor, or 5
      HT plus 0.5 ng/ml fibroblast growth factor. Cell number increased by 20-40% at 40
      h and 50-140% at 7 days. Protein content of cells treated with 5-HT was elevated
      by 20-40% at 7 days, whereas the rate of protein synthesis, measured by
      [35S]methionine incorporation, increased by 50-70% at 24 h. In the presence of 1
      microM 5-HT, cells enlarged by 70 and 100-200% at 40 h and 7 days,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304470
TI  - Regulation of serotonin-induced DNA synthesis of bovine pulmonary artery smooth
      muscle cells.
AB  - We have previously reported that serotonin [5-hydroxytryptamine (5-HT)]
      stimulates DNA synthesis of bovine pulmonary artery smooth muscle cells (SMC) by
      its high-affinity uptake. Uptake inhibitors, but not selective 5-HT receptor
      antagonists, prevented the stimulatory effect (S.-L. Lee and B. L. Fanburg. J.
      Cell. Physiol. 150:396-405, 1992). We have now further evaluated the mechanism by
      which 5-HT enhances SMC DNA synthesis. Although some serotonergic agonists
      mimicked this stimulation, selective 5-HT receptor agonists produced no or only
      minor and variable stimulatory effects. The action of 5-HT was not inhibited by
      inhibitors of phospholipases C and A2, the protein kinase C (PKC) inhibitors
      dihydrosphingosine and 1-(-isoquinolinylsulfonyl)-2 methylpiperazine (H-7), or
      down-regulation of PKC with phorbol 12,13-dibutyrate. Staurosporine, a reputed
      PKC and tyrosine kinase (TK) inhibitor, and genistein, a selective TK inhibitor,
      reversed the stimulatory effect of 5-HT in a dose-dependent manner. Before
      stimulation of thymidine incorporation into cellular DNA, 5-HT elevated c-myc and
      actin mRNAs. Imipramine, fluoxetine, staurosporine, and cholera toxin inhibited
      the stimulations of both DNA synthesis and c-myc and actin mRNA expressions by 5
      HT. Thus the data support a concept that 5-HT-induced thymidine incorporation by
      SMC involves membrane transport of 5-HT that initiates tyrosine phosphorylation.

PMID- 8304471
TI  - Contrasting effects of alveolar macrophages and neutrophils on asbestos-induced
      pulmonary epithelial cell injury.
AB  - Pulmonary toxicity from asbestos may be due in part to oxidant-mediated
      mechanisms. The purpose of this study was to determine whether alveolar
      macrophages (AM) contribute to asbestos-induced alveolar epithelial cell injury
      by oxidant-dependent mechanisms similar to that previously described for
      polymorphonuclear leukocytes (PMN). We assessed 51Cr release from cultured rat
      alveolar epithelial cells (RAEC) and transformed human pulmonary epithelial-like
      cell lines (rat L2 and human WI-26: HPEC). Amosite asbestos caused dose-dependent
      injury to both RAEC and L2 cells after an 18-h incubation period. Rat PMN
      increased asbestos-induced injury to RAEC (11 vs. 20% 51Cr release). In contrast,
      rat AM diminished asbestos-induced injury to RAEC and L2 cells by 60-80%. Human
      monocytes cultured for 72 h also attenuated asbestos-induced HPEC damage.
      Asbestos stimulated more H2O2 release from PMN than from AM isolated from the
      same rats (5.3 +/- 0.6 vs. 0.3 +/- 0.1 nmol x 10(6) cells-1 x 2h-1). The
      protective effect of rat AM, as opposed to PMN, was not due to differences in
      asbestos-induced toxicity to each cell type, since > 90% of AM and PMN were
      nonviable after 18 h. Transmission electron microscopy demonstrated comparable
      uptake of asbestos by AM and PMN after a 2-h incubation period. However, after an
      18-h exposure period, the PMN were completely lysed, whereas over 90% of the AM
      contained fibers, despite morphologic evidence of cytotoxicity. These results
      demonstrate that AM, unlike PMN, can reduce alveolar epithelial cell injury in
      this model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304472
TI  - Changes in cytosolic cGMP and calcium in airway smooth muscle relaxed by 3
      morpholinosydnonimine.
AB  - Nitrovasodilators relax airway smooth muscle by both guanosine 3',5'-cyclic
      monophosphate (cGMP)-dependent and cGMP-independent mechanisms and by mechanisms
      that reduce cytosolic calcium concentration ([Ca2+]i). This study was conducted
      to determine the relative importance of these mechanisms in relaxation of canine
      tracheal smooth muscle (CTSM) induced by 3-morpholinosydnonimine (SIN-1). We
      measured 1) the effect of SIN-1 on force, [cGMP]i, and [Ca2+]i, and 2) the
      ability of methylene blue (MB) to antagonize SIN-1-induced relaxation and cGMP
      accumulation. The ratio of fura 2 emission fluorescence intensities due to
      excitation at 340- and 380-nm wavelengths (F340/F380) was used as an index of
      [Ca2+]i. In strips contracted with 0.3 microM acetylcholine (ACh, n = 8) or 24 mM
      KCl (n = 8), SIN-1 (1-100 microM) caused a concentration-dependent decrease in
      force which was correlated with a concentration-dependent increase in [cGMP]i. MB
      (10 microM) proportionally attenuated both relaxation and cGMP accumulation. In
      fura 2-loaded strips contracted with 0.3 microM ACh (n = 7) or 30 mM KCl (n = 7),
      reductions in force induced by SIN-1 (1-100 microM) were accompanied by decreases
      in F340/F380. These findings suggest that in CTSM contracted with ACh or KCl, SIN
      1 causes relaxation which appears to be mediated by cGMP-dependent mechanisms
      that reduce [Ca2+]i.

PMID- 8304473
TI  - Effect of cigarette smoke and its condensates on alveolar epithelial cell injury
      in vitro.
AB  - The oxidant-antioxidant balance in the airspaces of the lungs may be critical in
      protecting the lungs from the effects of cigarette smoke. We studied the effect
      of cigarette smoke and its condensates on the detachment, attachment, and
      proliferation of the A549 human alveolar epithelial cell line, in an in vitro
      model of cell injury and regeneration and the protective effects of antioxidants.
      Whole and vapor phase cigarette smoke decreased 51Cr-labeled A549 cell
      attachment, increased cell detachment, and decreased cell proliferation, as
      assessed by [3H]thymidine uptake. Freshly isolated rat type II alveolar
      epithelial cells showed an enhanced susceptibility to smoke-induced cell lysis
      when compared with the A549 cell line. Reduced glutathione (GSH) (400 microM)
      protected against the effects of cigarette smoke exposure on cell attachment,
      proliferation, and detachment. Depletion of intracellular GSH with buthionine
      sulfoxamine enhanced the epithelial cell detachment injury produced by smoke
      condensates. We conclude that cigarette smoke and its condensates cause an
      oxidant-induced injury to A549 human type II alveolar epithelial cells. Both
      intra- and extracellular GSH have important roles in protecting epithelial cells
      from the injurious effects of cigarette smoke.

PMID- 8304474
TI  - Structural determinants of glomerular hydraulic permeability.
AB  - To elucidate which structures determine the resistance to water movement, we used
      a computational fluid dynamics approach to determine velocity and pressure fields
      within the glomerular capillary wall. The model included representations of the
      endothelial fenestrae, basement membrane, and epithelial filtration slits with
      slit diaphragms. The input data included dimensions of the various structures
      from previous electron microscopy studies, as well as the hydraulic permeability
      recently measured for isolated films of glomerular basement membrane in vitro.
      The hydraulic resistance of the endothelium was predicted to be small, whereas
      the basement membrane and filtration slits were each found to contribute roughly
      one-half of the total hydraulic resistance of the capillary wall. It was
      calculated that, for a given filtrate flux, the pressure drop within basement
      membrane in vivo is roughly twice that of "bare" or isolated basement membrane,
      because of the small fraction of basement membrane area exposed. The dominant
      resistance in the filtration slit was found to be the slit diaphragm. Predicted
      values for the overall hydraulic permeability of the capillary wall were within
      the experimental range derived from micropuncture measurements in normal rats.
      The model should be a useful tool for analyzing the effects of various structural
      changes on glomerular hydraulic permeability. This is illustrated by applying the
      model to recent physiological and morphometric data in nephrotic rats.

PMID- 8304475
TI  - Insulin-like growth factor I produces renal hyperfiltration by a kinin-mediated
      mechanism.
AB  - Insulin-like growth factor-I (IGF-I) infusion into rats and humans reduces renal
      vascular resistance and raises glomerular filtration rate (GFR) and renal plasma
      flow (RPF). To investigate whether kinins mediate the renal vasodilatory effects
      of IGF-I, we infused rats with IGF-I alone or in the presence of a B2 kinin
      receptor antagonist. Left kidney GFR, RPF, and kinin excretion were measured
      during infusion of vehicle and subsequently during 60-min infusion of IGF-I or
      IGF-I plus kinin antagonist. IGF-I was given as a bolus (150 micrograms/kg body
      wt), followed by infusion at a rate of 8.3 micrograms.kg-1 x min-1 for 60 min.
      The kinin antagonist was infused at a dose of 1 microgram.kg-1 x min-1 for 60 min
      before the start of IGF-I infusion. GFR and RPF increased significantly after IGF
      I infusion was begun, from baseline levels of 1.70 +/- 0.12 and 6.21 +/- 0.34 to
      2.12 +/- 0.11 and 7.91 +/- 0.29 ml/min, respectively, at 20 min (P < 0.001). This
      effect was maintained throughout 60 min of infusion. The increase in GFR and RPF
      was associated with a marked rise in urinary kinin excretion, from a baseline of
      8.51 +/- 6.7 to 24.7 +/- 6.7 pg/min at 20 min and 40.3 +/- 10.4 pg/min at 40 min
      (P < 0.001). Pretreatment with the kinin receptor antagonist blocked the rise in
      GFR and RPF in response to IGF-I. These data suggest that the renal vasodilatory
      effect of IGF-I is mediated by kinins.

PMID- 8304476
TI  - Natriuretic response to renal interstitial hydrostatic pressure during
      angiotensin II blockade.
AB  - Increases in renal interstitial hydrostatic pressure (RIHP) increase urinary
      sodium excretion (UNaV). Experimentally increasing RIHP by direct renal
      interstitial volume expansion (DRIVE) has been shown to decrease proximal tubule
      sodium reabsorption. The purpose of the present study was to investigate whether
      the renin-angiotensin system modulates the natriuretic response to DRIVE.
      Unilateral nephrectomy and implantation of two polyethylene matrices were
      performed 3 wk before the acute experiment. Fractional sodium excretion (FENa),
      RIHP, and glomerular filtration rate (GFR) were measured before and after DRIVE
      in control rats (n = 9) and in rats receiving the angiotensin II (ANG II)
      receptor antagonist, losartan potassium (10 mg/kg i.v.; n = 10). DRIVE was
      achieved by infusing 100 microliters of 2.5% albumin solution directly into the
      renal interstitium. GFR remained unchanged by DRIVE in both groups. In control
      animals, DRIVE significantly increased both RIHP (delta 3.8 +/- 0.5 mmHg) and
      FENa (delta 0.92 +/- 0.19%). In the losartan-treated group, RIHP (delta 2.8 +/-
      0.4 mmHg) and FENa (delta 1.93 +/- 0.41%) also significantly increased. The
      natriuretic response to DRIVE was significantly enhanced during ANG II receptor
      blockade compared with control animals (delta UNaV/delta RIHP = 2.01 +/- 0.67 vs.
      0.44 +/- 0.17 mu eq.min-1 x mmHg-1, respectively; P < 0.05). These results
      suggest that the blockade of angiotensin enhances the natriuretic response to
      increased RIHP during DRIVE.

PMID- 8304477
TI  - Augmentation of intrarenal angiotensin II levels by chronic angiotensin II
      infusion.
AB  - The objective of this study was to investigate the singular role of elevated
      angiotensin II (ANG II) levels in the development of two-kidney, one-clip (2K1C)
      Goldblatt hypertension in the rat and specifically in the altered intrarenal ANG
      II levels that occur in the nonclipped kidney. As a substitute for the clipped
      kidney, chronic delivery of ANG II (40 ng/min) via an osmotic minipump implanted
      subcutaneously was used to mimic plasma ANG II levels observed in 2K1C rats
      during the developmental phase of hypertension. Arterial pressure increased
      gradually over a period of 14 days, and a pressure profile similar in magnitude
      and temporal pattern to that of the 2K1C rats was observed. Systemic ANG II was
      elevated to similar levels in the 2K1C (60 +/- 13 fmol/ml) and ANG II-infused
      rats (72 +/- 15 fmol/ml) compared with intact two-kidney control animals (31 +/-
      6 fmol/ml; P < 0.05) or uninephrectomized rats (13 +/- 1 fmol/ml; P < 0.05).
      Although renin content was markedly suppressed (80%), intrarenal ANG II content
      of the contralateral kidneys of the 2K1C groups (86 +/- 12 fmol/g) and the ANG II
      infused group (150 +/- 17 fmol/g) was greater than that of the two-kidney control
      (53 +/- 7 fmol/g; P < 0.05) and uninephrectomized control animals (42 +/- 5
      fmol/g; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304478
TI  - Hepatocyte growth factor accelerates recovery from acute ischemic renal injury in
      rats.
AB  - Effects of hepatocyte growth factor (HGF) administration were examined in a model
      of acute ischemic renal injury induced by bilateral renal artery occlusion in
      rats. Compared with rats administered vehicle, rats administered 20 micrograms
      HGF subcutaneously 30 min postischemia had significantly lower serum creatinine
      and blood urea nitrogen levels over the course of 7 days postocclusion, enhanced
      insulin clearances measured on day 2 postocclusion, reduced mortality, and much
      less injury evident by examination of kidney histologies 7 days postinjury. The
      tubular regeneration that occurred postischemic injury was reflected by increased
      incorporation of 5-bromo-2'-deoxyuridine (BrdU) in cortical tubular epithelium
      compared with incorporation in kidneys from noninjured rats. HGF enhanced BrdU
      incorporation compared with vehicle, indicating enhanced mitogenesis. The weight
      loss that occurs postischemic injury was not ameliorated by the dose of HGF we
      employed. We conclude that administration of HGF postischemic injury to rats
      stimulates the recovery of normal kidney function and the regeneration of
      proximal tubular epithelium.

PMID- 8304479
TI  - Calcium and free radicals in hypoxia/reoxygenation injury of renal epithelial
      cells.
AB  - Hypoxia and reoxygenation (H/R) generate oxygen free radicals that result in
      renal cell injury. We tested the roles of calcium and calmodulin in mediating
      xanthine oxidase-derived oxygen free radical production during H/R. Lowering
      extracellular Ca2+ attenuated lethal cell injury. H/R increased superoxide
      radical production over basal levels, whereas removing extracellular Ca2+ before
      hypoxia decreased superoxide radical production to basal levels. Pretreatment
      with either 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride or
      thapsigargin, to inhibit release or deplete stores of intracellular Ca2+, did not
      affect injury following H/R. Ionomycin increased lactate dehydrogenase release
      during H/R but did not increase superoxide radical to levels greater than that
      observed for H/R alone. The calmodulin inhibitors trifluoperazine, calmidazolium,
      or N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide decreased cell injury to
      varying degrees. Trifluoperazine also decreased superoxide radical production
      during H/R and was shown to inhibit the conversion of xanthine dehydrogenase to
      xanthine oxidase. Cell injury and superoxide radical production correlated with
      cytosolic free Ca2+ during H/R as determined with the Ca(2+)-sensitive
      fluoroprobe indo 1. Cytosolic free Ca2+ increased slightly during hypoxia and
      showed a dramatic increase as soon as cells were reoxygenated. Cells incubated in
      a Ca(2+)-free medium actually showed a small decrease in intracellular Ca2+
      despite H/R. In summary, Ca2+ derived from extracellular sources promoted
      superoxide radical production and renal cell injury by a calmodulin-dependent
      conversion of xanthine dehydrogenase to xanthine oxidase, a major source of
      oxygen free radicals during H/R.

PMID- 8304480
TI  - Effect of an endothelin-receptor antagonist on ischemic acute renal failure.
AB  - In the isolated perfused rat kidney, endothelin (ET) added to the perfusate at
      concentrations ranging from 50 to 500 pmol/l resulted in a dose-dependent
      reduction in renal perfusate flow (RPF) and inulin clearance (CIn). The decrease
      in RPF (17 +/- 3 vs. 34 +/- 3 ml.min-1 x g-1; P < 0.01 compared with control) and
      CIn (89 +/- 13 vs. 317 +/- 19 microliters.min-1 x g-1; P < 0.01 compared with
      control) by ET (500 pmol/l) was prevented by the ET antagonist BQ-123 (10
      microM), with full recovery of RPF [36 +/- 2 vs. 34 +/- 3 ml.min-1 x g-1; not
      significant (NS) compared with control] and CIn (299 +/- 51 vs. 317 +/- 19
      microliters.min-1 x g-1; NS compared with control). In the absence of ET,
      perfusion of the kidney with a similar concentration of BQ-123 (10 microM) did
      not induce any changes in RPF (36 +/- 5 vs. 34 +/- 3 ml.min-1 x g-1; NS compared
      with control) or CIn (320 +/- 14 vs. 317 +/- 19 microliters.min-1 x g-1; NS
      compared with control). After 60 min of arterial clamping, BQ-123 (10 microM)
      given before the onset of ischemia and during reflow improved CIn (88 +/- 4 vs.
      19 +/- 3 microliters.min-1 x g-1; n = 6, P < 0.01) and net tubular sodium
      reabsorption (TNa) compared with no treatment. On the other hand, the same dose
      (10 microM) of BQ-123 given only during the reperfusion period was not effective
      in preventing the decreases in either CIn or TNa.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8304481
TI  - Functional and cytoskeletal changes induced by sublethal injury in proximal
      tubular epithelial cells.
AB  - Mouse proximal tubular (MPT) cells in culture were subjected to ATP depletion by
      incubating them with cyanide in the absence of dextrose for 1 h. This insult
      resulted in marked alterations in the actin cytoskeleton. These changes were not
      associated with a decrease in cell viability and thus reflected sublethal injury.
      The effect of sublethal injury on the functional integrity of the intercellular
      tight junction (TJ) was then examined in MPT cell monolayers grown on permeable
      supports. During chemical anoxia, monolayer permeability to the paracellular
      marker mannitol progressively increased to 297 +/- 62% of baseline after 1 h.
      Chemical anoxia also caused a reversible loss in cell-substrate adhesion when MPT
      cells were studied as confluent monolayers or as single cells. Thus disruption of
      the actin cytoskeleton in nonlethally injured cells results in important
      reversible alterations in renal epithelial function characterized by impairment
      of the "gate" function of the TJ as well as impaired cell-substrate adhesion. We
      hypothesize that sublethal epithelial cell injury without accompanying necrosis
      may contribute to the decrement in renal function characteristic of ischemic
      renal injury.

PMID- 8304482
TI  - Effect of dietary sodium chloride on insulin receptor number and mRNA levels in
      rat kidney.
AB  - Insulin has been postulated to play a role in the pathophysiology of essential
      hypertension via an antinatriuretic action. To further explain the sodium insulin
      interaction in the kidney, we studied effects of different salt intakes on
      insulin receptor binding and mRNA levels in tissues from rats maintained on
      0.07%, 0.3%, or 7.5% NaCl for 14 days. Scatchard analysis of competition data
      from in situ autoradiography studies resulted in curvilinear profiles, indicating
      the presence of either two classes of receptors or a single class of receptors
      with a negative cooperative hormone-receptor interaction. When data were analyzed
      using the two-site model, binding capacity of the high-affinity receptor site was
      significantly less in high-salt-fed rats. No significant differences between
      dietary groups were observed in apparent dissociation constants of the two
      receptor sites or in maximal binding capacity of the low-affinity, high-capacity
      site. Analysis of insulin binding to glomeruli, cortex, outer medulla, and inner
      medulla indicated that the high-salt diet was associated with decreased receptor
      density in all regions studied. Insulin receptor mRNA, as quantified by Northern
      and slot blot analysis, was inversely related to salt intake in absence of a
      change in plasma glucose, insulin, and corticosterone levels. Both 7.2- and 9.4
      kb transcripts were similarly affected by dietary sodium content. Plasma renin
      concentration and renal renin mRNA levels were decreased but blood pressure was
      not affected by high-salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304483
TI  - Regulation of prostaglandin endoperoxide synthase gene expression in rat
      mesangial cells by interleukin-1 beta.
AB  - In primary cultures of rat mesangial cells from passage 3 to 6, interleukin-1
      beta (IL-1) induced a time-dependent increase in prostaglandin E2 (PGE2)
      formation and release into the extracellular medium. This increase was associated
      with a dramatic upregulation of the steady-state levels of mRNA for the
      prostaglandin endoperoxide synthetase (PES)-2 gene transcript as demonstrated by
      Northern analysis. In contrast, there did not appear to be a significant increase
      in the mRNA levels for a 2.8-kb transcript for the PES-1 gene. At 18 h of
      exposure to IL-1, the steady-state level of message for PES-2 remained elevated
      at 50% of the 2-h time point. Culturing the cells in the presence of
      cycloheximide and IL-1 demonstrated a superinduction of the PES-2 message without
      any change in PES-1 message. The tumor-promoting phorbol ester, phorbol myristate
      acetate (PMA), was also associated with an upregulation of the message for the
      PES-2 gene and did not influence the levels of the message for the PES-1 gene as
      demonstrated by Northern analysis. Dexamethasone (Dex) inhibited to control
      levels the induction by PMA, but the induction of the message by IL-1 was only
      inhibited 30%. Despite 70% of the message being present by 2 h of induction, Dex
      was capable of totally inhibiting the inductive effect of IL-1 with respect to
      PGE2 biosynthesis. Immunocytochemical studies demonstrated a dramatic induction
      of PES-2 protein by IL-1, which was inhibited by Dex. The data suggest that Dex
      inhibits the translation of the PES-2 protein.

PMID- 8304485
TI  - Postnatal maturation of potassium transport in rabbit cortical collecting duct.
AB  - Clearance studies in newborns demonstrate low rates of urinary excretion of
      potassium, suggesting that the neonatal kidney contributes to the conservation of
      potassium necessary for growth. Because the cortical collecting duct (CCD) is a
      primary site for potassium secretion in the adult, we sought to examine the
      transport capacity of this segment for potassium during postnatal maturation.
      CCDs isolated from rabbits of various ages (5-6 animals/age group) were
      microperfused in vitro with solutions simulating plasma. The concentrations of
      potassium in samples of collected fluid, measured by helium glow photometry, were
      used to calculate net transport. At a flow rate of approximately 1.6 nl.min-1 x
      mm-1 net potassium secretion was absent at birth, first became evident at 4 wk of
      age (-11.08 +/- 2.39 pmol.min-1 x mm-1), and increased sharply thereafter to
      reach mature rates (-23.08 +/- 3.47 pmol.min-1 x mm-1; P < 0.05) by 6 wk of age.
      To determine whether low distal tubular flow rates limit net potassium secretion
      in the neonate, we perfused CCDs at two or more flow rates in the 0.5-5 nl.min-1
      x mm-1 range. In CCDs taken from animals > or = 6 wk of age, potassium secretion
      showed a significant linear correlation with flow rate (y = -10.0x - 7.45; r =
      0.87; n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304484
TI  - Mechanism of endothelin activation of phospholipase A2 in rat renal medullary
      interstitial cells.
AB  - Previous studies from this laboratory have demonstrated that endothelin-1 (ET)
      stimulates phosphatidylinositol (PI) hydrolysis, activates dihydropyridine
      insensitive Ca2+ channels, and promotes prostaglandin E2 (PGE2) accumulation in
      cultured rat renal medullary interstitial cells (RMIC). The mechanism whereby ET
      augments PGE2 production was explored in the current study. ET-evoked PGE2
      accumulation proceeded independent of large increments in cytosolic free Ca2+
      concentration ([Ca2+]i), derived from either extracellular or intracellular
      sources. Chelation of intracellular Ca2+ with 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid eliminated ET-evoked PGE2 production, indicating that
      eicosanoid production was nonetheless a Ca(2+)-requiring process. Nanomolar
      concentrations of phorbol 12-myristate 13-acetate (PMA) alone did not stimulate
      PGE2 production, nor did PMA alter ET-stimulated PGE2 accumulation. Furthermore,
      downregulation of protein kinase C (PKC) by prolonged exposure of cells to PMA
      did not mitigate ET-mediated PGE2 production, demonstrating that PKC stimulation
      was not required for PGE2 production. ET stimulated PGE2 accumulation despite PI
      specific phospholipase C (PI-PLC) inhibition by nanomolar concentrations of PMA,
      indicating that eicosanoid production was not a downstream event of PI
      hydrolysis. ET stimulated arachidonic acid metabolite release in parallel with a
      loss of label from membrane phospholipids. Phosphatidylethanolamine was the
      preferred substrate for ET-mediated activation of phospholipase A2 (PLA2).
      Immunocytochemical studies including immunostaining, immunoblotting, and
      immunoprecipitation confirmed the presence of cytosolic PLA2 (cPLA2) in RMIC. In
      summary, ET stimulation of PGE2 production in RMIC is mediated via agonist
      activation of cPLA2 independent of activation of PI-PLC, suggesting direct
      coupling to the ET receptor. Constitutive levels of [Ca2+]i rather than abrupt
      increments in [Ca2+]i are sufficient for activation of this receptor-effector
      system, with no obligatory requirement for PKC.

PMID- 8304486
TI  - Minealocorticoid receptors and 11 beta-steroid dehydrogenase activity in renal
      principal and intercalated cells.
AB  - Aldosterone exerts complex effects on the cortical collecting duct (CCD): it
      increases Na+ and K+ transport, and it also influences H+ and HCO3 transport.
      Whether these latter effects represent direct action of aldosterone on
      intercalated cells (ICC) or are secondary to changes in the transport of other
      electrolytes is unclear. Because the presence of specific receptors is the
      prerequisite of a direct steroid action, and mineralocorticoid receptors (MR)
      have not yet been demonstrated in ICC, in this study we determined the density of
      MR directly in isolated principal cells (PC) and beta-ICC. Purified populations
      of these two cell types were obtained from rabbit renal cortex by
      immunodissection and fluorescence-activated cell sorting. We found that both PC
      and beta-ICC contained a significant number of MR, although receptor density was
      higher in PC than in beta-ICC (6,704 +/- 912 vs. 2,181 +/- 388 MR sites/cell; P <
      0.001). 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD), an enzyme that is
      present predominantly in mineralocorticoid target cells, exhibited a distribution
      similar to that of MR in the two cell types. 11 beta-OHSD activity, determined by
      measuring the rate of conversion of [3H]corticosterone to 11
      dehydrocorticosterone, was 1.08 +/- 0.14 and 0.34 +/- 0.08 fmol.min-1 x 1,000
      cells-1 (P < 0.001) in intact PC and beta-ICC, respectively. 11 beta-OHSD in both
      cell types utilized NAD as cofactor. These results suggest that beta-ICC are
      potential direct targets of aldosterone and that MR in both PC and beta-ICC are
      protected by 11 beta-OHSD.

PMID- 8304487
TI  - Glomerular endothelial cells in culture express and secrete vascular endothelial
      growth factor.
AB  - Vascular endothelial growth factor (VEGF) is a specific growth factor for
      endothelial cells, and its abundant expression has been reported in kidney
      glomeruli. In this study, we focused on glomerular endothelial cells (GEN) as a
      possible source of VEGF secretion and sought to uncover a potential autocrine
      role of VEGF for GEN. Ribonuclease protection assay demonstrated VEGF mRNA
      expression in cultured GEN, and 46-kDa VEGF protein was detected in the
      conditioned medium by immunoblot analysis using polyclonal antibody raised
      against the NH2-terminal portion of VEGF. Removal of fetal bovine serum (FBS)
      from the culture medium for 2 h decreased VEGF mRNA abundance, which was restored
      by the readdition of FBS (10%) within 2 h. The effect of FBS was completely
      abolished by protein kinase inhibitor H-7 (10 microM), suggesting that FBS
      stimulated VEGF mRNA induction involves activation of protein kinases. The
      treatment of GEN with 10(-7) M 12-O-tetradecanoylphorbol-13-acetate (TPA)
      increased the VEGF mRNA abundance fivefold, supporting the idea that VEGF
      expression is regulated by protein kinase C. [3H]thymidine incorporation into GEN
      treated with TPA (10(-7) M) was inhibited by neutralizing antibody for VEGF. Thus
      VEGF was identified as an autocrine growth factor for GEN in vitro. Its
      physiological role might be the regulation of GEN proliferation, and the
      induction of VEGF expression by FBS and TPA suggests its involvement in the
      response of glomerular capillary endothelial cells to injury in certain
      pathophysiological states.

PMID- 8304488
TI  - Angiotensin II suppression is a major factor permitting excretion of an acute
      sodium load in humans.
AB  - We examined the role of circulating angiotensin II (ANG II) in the excretion of
      an acute Na+ load in eight healthy subjects given 2 liters 0.9% saline in a
      placebo-controlled crossover study. On the control day, plasma ANG II decreased
      to 40-60% of basal values and 35 +/- 9 (SE) mmol of Na+ was excreted in the 5 h
      after the start of saline infusion. When ANG II was infused to maintain plasma
      ANG II levels at around basal values (6.6 +/- 1.6 pmol/l), only 7 +/- 8 mmol of
      Na+ was excreted in the same period (P < 0.05). In a previous similar study in
      which the fall in aldosterone was prevented by infusion of aldosterone, 16 +/- 16
      mmol of Na+ was excreted vs. 36 +/- 16 mmol on the control day in comparable 5-h
      periods. Suppression of ANG II is one of the major factors permitting the acute
      increase in Na+ excretion after an intravenous Na+ load. ANG II has direct
      actions on Na+ excretion in addition to its effects on aldosterone.

PMID- 8304489
TI  - Intracellular modulation of acid secretion in rat inner medullary collecting duct
      cells.
AB  - In this study we defined some of the important elements in the acidification
      process of rat inner medullary collecting duct (IMCD) cells in culture. After
      cell acidification, i.e., cell pH (pHi) = 6.51 +/- 0.02, pHi increased 0.046 +/-
      0.003 units/min. N-ethylmaleimide, N,N'-cyclohexylcarbodiimide, and bafilomycin
      reduced this rate by over 85%. In contrast, omeprazole and Sch-28080 had no
      effect. 1,2-Bis(2-aminophenoxy)ethane-N,N,N,N'-tetraacetic acid, which prevents a
      rise in cell Ca2+ concentration ([Ca2+]i) reduced the rate of pHi recovery to
      0.013 +/- 0.002 units/min. Calmodulin inhibitors or disruption of cytoskeletal
      elements with cytochalasin B and colchicine also reduced pHi recovery
      significantly. In addition, these cells contain acidic vesicles and undergo pHi
      regulated endocytosis and exocytosis, which are inhibited by disrupting the
      cytoskeleton. We conclude that, in our cultured line of rat IMCD cells, proton
      secretion is mediated by an H(+)-adenosinetriphosphatase. Changes in pHi produce
      alterations in acid secretion through a signal cascade that requires changes in
      [Ca2+]i, activation of calmodulin, an intact cytoskeleton, and alteration in the
      rate of exocytosis and endocytosis.

PMID- 8304490
TI  - New experiments on shear modulus of elasticity of arteries.
AB  - Although the mechanical properties of blood vessels have been studied
      extensively, the shear modulus of the blood vessel wall is still unknown. New
      data on the shear modulus of elasticity of rat arteries and its variation with
      axial stretch and blood pressure are presented. The data were obtained from a new
      instrument designed and constructed by us to perform simultaneous torsion,
      inflation, and longitudinal stretching tests. It was found under physiological
      conditions (pressure = 120 mmHg or 16 kPa; longitudinal stretch = 1.2 relative to
      zero-stress state), the shear modulus of normal rat thoracic aorta is G = 137 +/-
      18 kPa. The difference of shear modulus at body temperature (37 degrees C) and
      room temperature (25 degrees C) is within 10%. The shear modulus varies
      significantly with changing longitudinal and circumferential strains in
      proportion to the strain energy due to these strains. A constitutive equation
      based on a pseudo strain energy function is proposed. The vessel wall is not
      transversely isotropic in the incremental sense. When the rat was subjected to
      high blood pressure due to constriction of its aorta, the shear modulus does not
      vary significantly with the length of time the animal was subjected to
      hypertension.

PMID- 8304491
TI  - Tyrosine kinase inhibitors impair fibroblast growth factor signaling in coronary
      endothelial cells.
AB  - We examined the effect of various tyrosine kinase inhibitors on basic fibroblast
      growth factor (bFGF)-induced cell signaling and DNA synthesis in coronary venular
      endothelial cells (CVEC). Two tyrosine kinase inhibitors, genistein and methyl
      2,5-dihydroxycinnamate, showed reversible, dose-dependent inhibition of bFGF
      stimulated DNA synthesis in CVEC with half-maximal inhibitory concentrations of
      12 and 3 microM, respectively. Both compounds exhibited preferential inhibition
      of bFGF vs. serum-induced DNA synthesis. bFGF stimulated increased tyrosine
      phosphorylation of CVEC cellular proteins, including the FGF receptor, which were
      visible within 1 min of treatment. Concomitant with their effect on DNA
      synthesis, both compounds exhibited dose-dependent inhibition of tyrosine
      phosphorylation of intracellular substrates induced by bFGF. A 2-h pretreatment
      of quiescent CVEC with genistein blocked nuclear translocation but not
      cytoplasmic internalization of bFGF, whereas the same treatment with methyl 2,5
      dihydroxycinnamate inhibited both processes. These results suggest that
      activation of bFGF receptor tyrosine kinase activity plays a role in nuclear
      translocation of bFGF and initiation of DNA synthesis in endothelial cells.

PMID- 8304492
TI  - Hydrogen peroxide cytotoxicity in cultured cardiac myocytes is iron dependent.
AB  - Because of its potential importance in injury during myocardial ischemia and
      reperfusion, we assessed mechanisms of hydrogen peroxide (H2O2) cytotoxicity in
      cultured chick embryo cardiac myocytes. Injury was quantitated by release of
      lactate dehydrogenase (LDH) or 51Cr, both of which correlated with loss of cell
      viability assessed by trypan blue exclusion. The iron chelator deferoxamine (0.25
      2 mM), but not equimolar iron-loaded deferoxamine, markedly reduced LDH and 51Cr
      release. Injury was also prevented or attenuated by the diffusible reactive
      oxygen metabolite scavengers dimethylthiourea (10-20 mM) and N-(2
      mercaptopropionyl)-glycine (20 mM). The hydroxyl radical scavenger, dimethyl
      sulfoxide (200-400 mM), also reduced injury. Other scavengers that probably
      remained extracellular, superoxide dismutase and mannitol, were ineffective.
      Thus, with exposure of cardiac myocytes to H2O2, cytotoxicity requires reactions
      catalyzed by intracellular iron.

PMID- 8304493
TI  - Isolated cardiac myocytes are sensitized by hypoxia-reoxygenation to neutrophil
      released mediators.
AB  - We exposed isolated rat cardiac myocytes to 20 min of hypoxia followed by 20 min
      of reoxygenation and observed the effect of supernatants of stimulated
      neutrophils [polymorphonuclear leukocytes (PMNs)] given at the beginning of
      reoxygenation. PMN supernatants induced cardiac myocyte injury, which was
      characterized by a significant (P < 0.01) reduction in cell viability to 53 +/-
      3%, vs. 84 +/- 3% in rat myocytes subjected to hypoxia-reoxygenation (H/R) alone.
      The PMN supernatants also resulted in elevated creatine kinase (CK) activities in
      the myocyte medium. To examine specific PMN-released mediators that may
      contribute to this cell death, we studied the effects of hydrogen peroxide
      (H2O2), elastase, and platelet-activating factor on H/R cardiac myocytes.
      Incubation of myocytes after hypoxia with 10, 50, and 100 microM H2O2 decreased
      viability in a concentration-dependent manner (from 83 +/- 2 to 37 +/- 2%; P <
      0.01). CK release of H/R myocytes was also significantly increased by 100 microM
      H2O2 (to 28 +/- 5 from 12 +/- 1% for H/R alone; P < 0.01). Similarly, elastase (5
      micrograms/ml) given after hypoxia significantly reduced cardiac myocyte
      viability during reoxygenation (viability 58 +/- 1 vs. 85 +/- 1% H/R alone; P <
      0.05) and increased CK release (to 29 +/- 3 from 11 +/- 1% for H/R alone; P <
      0.01), an effect that was abolished by L-680,833, an elastase inhibitor. Unlike
      H2O2 and elastase, platelet-activating factor had no significant effect on
      myocyte viability or CK release after H/R.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304494
TI  - Stretch preconditions canine myocardium.
AB  - Preconditioning is believed to be directly triggered by brief ischemia
      reperfusion. However, brief ischemia results in transient dilation (or
      stretching) of the heart. We therefore sought to determine whether stretch per
      se, induced by rapid volume overload instead of brief coronary occlusion, could
      precondition the heart via stretch-activated ion channels. Forty-two anesthetized
      dogs underwent 1 h of coronary artery occlusion followed by 4.5 h of reperfusion.
      Before this, each dog underwent either no intervention (control) or acute volume
      overload. In three additional groups, Gd3+, a potent blocker of stretch-activated
      channels was injected as a bolus into the left atrium of each dog at the onset of
      the treatment period. Then the dogs underwent either acute volume overload, a 5
      min episode of coronary occlusion followed by 10 min of reperfusion, or no
      intervention. Myocardial stretch significantly reduced infarct size after a
      subsequent 60-min ischemic insult. Protection afforded by stretch was completely
      prevented by Gd3+. Reduction in infarct size afforded by ischemic preconditioning
      was partially reversed by Gd3+. Gd3+ per se did not, however, alter the extent of
      necrosis. The present study suggests that myocardial stretch per se can
      precondition the canine heart, probably by activation of stretch-activated ion
      channels.

PMID- 8304495
TI  - Enhanced resistance artery sensitivity to agonists under isobaric compared with
      isometric conditions.
AB  - We have compared the responsiveness of rabbit mesenteric resistance arteries with
      agonists under isometric and isobaric conditions. When pressurized (60 mmHg),
      arteries spontaneously reduced their diameter by 18.1%. An equivalent isometric
      stress did not generate force in a "wire" myograph. Subsequently, much higher
      concentrations of norepinephrine (NE) and histamine were required to cause
      isometric contractions than were needed to reduce vascular diameter of
      pressurized vessels, whereas angiotensin II produced a maintained response only
      in pressurized arteries. Reducing transmural pressure to 20 mmHg abolished
      pressure-induced myogenic tone and decreased arterial sensitivity to NE. Under
      isometric conditions, partial depolarization with KCl increased sensitivity to NE
      and histamine to within the concentration range effective in pressurized vessels
      and also "revealed" responses to angiotensin II. The membrane potential of the
      vascular smooth muscle cells under partially depolarized conditions was similar
      to that found in vivo and in vessels studied isobarically. These observations
      demonstrate a fundamental interaction between pressure-induced myogenic tone and
      the sensitivity of resistance arteries to vasoactive stimuli. This influence was
      mimicked in isometrically mounted vessels by partial depolarization, indicating a
      possible pivotal role for membrane potential in determining the reactivity of the
      resistance vasculature.

PMID- 8304496
TI  - Substantial reductions in blood pressure after bilateral nephrectomy in fetal
      sheep.
AB  - The role of the kidneys in the maintenance of arterial blood pressure was
      examined in fetal sheep. Surgery was performed on 11 pregnant sheep (8 twin
      pregnancies) at approximately 125 days. All 19 fetuses were instrumented with
      hindlimb arterial and venous catheters. Eleven of the fetuses (but only 1 of each
      twin) were also bilaterally nephrectomized. Fetal arterial blood pressure was
      measured several times between 2 and 14 days after surgery. Arterial blood
      pressure in the intact fetuses increased from 44 +/- 1 to 47 +/- 1 mmHg (SE) but
      gradually decreased from 37 +/- 4 to 25 +/- 3 mmHg in the nephrectomized group.
      Whereas the arterial blood pressures measured on the first day of the experiment
      were not statistically significantly different between the two groups, by the
      final day of the experiment the arterial blood pressure of the intact fetuses was
      much higher than that of the nephrectomized fetuses. Venous blood pressure was
      similar in the two groups. We conclude that bilateral nephrectomy in fetal sheep
      not only stops the normal gestational increase in arterial blood pressure but
      also leads to a progressive decline.

PMID- 8304497
TI  - Platelets do not modulate leukocyte-mediated coronary microvascular damage during
      early reperfusion.
AB  - Several studies indicate that leukocytes and platelets exacerbate the compromise
      of myocardial function that occurs after ischemia-reperfusion (I/R). However, it
      is unclear whether both leukocytes and platelets must be present to mediate
      coronary microvascular damage early during reperfusion after ischemia. To examine
      the effects of leukocytes and platelets on microvascular damage after I/R, we
      measured transcoronary albumin extravasation (O/I), perfused coronary capillary
      density (Caps), and transcoronary albumin extravasation per perfused capillary
      [(O/I)/Caps] in isolated rat hearts perfused with a Krebs-albumin-red blood cell
      solution [K(2)RBC], whole rat blood diluted with Krebs buffer (DWB), leukocyte
      free, platelet-rich DWB (LFB), or leukocyte-rich, platelet-free DWB (LRB) before
      and after a 30-min period of global, no-flow ischemia. We found that in isolated
      hearts perfused with K(2)RBC before ischemia, O/I values were significantly
      increased (+68%, P < 0.01) and Caps values were significantly decreased (-25%, P
      < 0.05) after 25 min of reperfusion. A similar pattern of O/I values (+72%, P <
      0.01) and Caps values (-40%, P < 0.05) was observed in hearts perfused with LFB.
      These effects were exacerbated in hearts perfused with DWB or LRB. O/I values
      were increased 90% (P < 0.01), and Caps values were decreased 62% (P < 0.01) in
      the DWB-perfused hearts. Similar increases in O/I values (+82%, P < 0.01) and
      decreases in Caps values (-65%, P < 0.01) were measured in the LRB-perfused
      hearts. Additionally, (O/I)/Caps values were significantly increased in the
      hearts perfused with DWB (+93%, P < 0.01) and LRB (+84%, P < 0.01) compared with
      the hearts perfused with K(2)RBC or LFB. These results suggest that interactions
      between leukocytes and platelets are not requisite for the development of
      coronary microvascular damage early during reperfusion after ischemia.

PMID- 8304498
TI  - Inhibition of metabolism abolishes transient outward current in rabbit atrial
      myocytes.
AB  - Outward currents were measured in single rabbit atrial myocytes using the whole
      cell configuration of the patch-clamp technique in the presence of tetrodotoxin
      (5-10 microM) and MnCl2 (2 mM) to block inward currents. Depolarizing voltage
      clamp steps from a holding potential of -80 mV elicited a predominant 4
      aminopyridine (4-AP)-sensitive transient outward current (Ito). Inhibitors of
      oxidative metabolism, 2,4-dinitrophenol (DNP; 100 microM) and cyanide (3 mM)
      abolished Ito and caused a large increase in the steady-state outward current.
      This steady-state outward current was inhibited by glibenclamide (5 microM), a
      blocker of the ATP-regulated potassium current (IKATP). In the presence of DNP,
      glibenclamide (5 microM) not only inhibited IKATP but also partially restored
      Ito. Absence of ATP from the pipette produced effects on outward currents similar
      to those induced by DNP or cyanide. We conclude that metabolic inhibition
      abolishes Ito in rabbit atrial myocytes and suggest that ATP may be required for
      the activation of the channel.

PMID- 8304499
TI  - Effect of bacterial lipopolysaccharide on function of rat small femoral arteries.
AB  - The effects of endotoxin on endothelial and smooth muscle function were
      investigated in small femoral arteries removed from rats 4 h after
      intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS; 20 mg/kg)
      or solvent. In the absence of L-arginine in the organ bath, the sensitivity of
      the arteries to norepinephrine (NE) was decreased only slightly, and the relaxing
      effects of neither 3-morpholinosydonimine-N-ethyl-carbamide (SIN-1), a nitric
      oxide (NO) donor, nor acetylcholine (ACh) were modified by LPS treatment despite
      morphological damage to the endothelium seen with scanning electron microscopy.
      However, L-arginine (30 microM to 1 mM), which had no effect on control vessels,
      caused a rapid and stereospecific relaxation of arteries from LPS-treated rats
      that was abolished by both NG-nitro-L-arginine methyl ester (1 mM), a NO synthase
      inhibitor, and methylene blue, an inhibitor of the activation of guanylyl cyclase
      by NO. The relaxing effect of L-arginine was observed in the absence of
      endothelium, although it was significantly greater in its presence. In addition,
      a 30-min exposure to extracellular L-arginine (100 microM) moderately but
      significantly decreased the sensitivity to ACh and SIN-1 of vessels from LPS
      treated but not from control rats. These results indicate that LPS treatment
      induced a NO synthase activity in smooth muscle cells of rat small femoral
      arteries and that the resulting relaxation was dependent on extracellular L
      arginine in these resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304500
TI  - Short-term cardiovascular responses to a step decrease in peripheral conductance
      in humans.
AB  - A step decrease in total peripheral conductance (TPC) was introduced in 10
      healthy volunteers by rapid inflation to suprasystolic pressure of bilateral
      thigh cuffs. This provoked a sudden statistically significant increase in mean
      arterial blood pressure (MAP) of 5 mmHg during supine rest and of 8 mmHg during
      moderate supine exercise by the quadriceps muscles. Central venous pressure was
      not changed by cuff inflation. The increase in MAP was blunted by a rapid but
      transient decrease in both heart rate (HR) and cardiac stroke volume. At rest, a
      gradual increase in TPC, starting after 4 s, nearly fully restored MAP to its
      original value at 10 s. During exercise, MAP was halfway corrected at 10 s but
      then started to increase again, probably as a result of an ischaemic muscle
      pressor response. After cholinergic blockade by atropine, the immediate HR
      response was eliminated, but HR decreased gradually after a delay of 3 s. The
      time development of the slow increase in TPC was not changed by atropine. In
      conclusion, the regulatory correction of a sudden increase in arterial pressure
      in supine unanesthetized healthy humans is achieved through an immediate
      transient parasympathetic bradycardia during the first few seconds and a more
      gradual sympathetic peripheral vasodilation after 4 s. After cholinergic
      blockade, a slow presumably sympathetic HR response was observed.

PMID- 8304501
TI  - Relation between baroreflex sensitivity and cardiac vagal tone in humans.
AB  - The extent of dependence of cardiac vagal tone on arterial baroreceptor input has
      been studied in 12 healthy, young adult subjects. Cardiac vagal tone was defined
      as the chang in R-R interval after complete cholinergic blockade by atropine.
      Baroreflex sensitivity was determined with the "Oxford-method": R-R interval was
      regressed against systolic pressure. The interindividual correlation between
      cardiac vagal tone and baroreflex sensitivity for falling pressures was found to
      be significant, but not close (R = 0.81, P = 0.002). In each subject, the
      baroreflex regression line for falling pressures was extrapolated to the post
      atropine R-R interval level; 50 mmHg was considered as minimum and 80 mmHg as
      maximum threshold level for the integrated baroreflex. From the relation between
      the individual regression lines and the minimum and maximum threshold levels, it
      was concluded that cardiac vagal tone could be generated by both baroreflex
      dependent and -independent mechanisms, the ratio of which varies in different
      individuals, with the baroreflex-dependent mechanism being the dominant factor.

PMID- 8304502
TI  - Interstitial exclusion of IgG in rat tissues estimated by continuous infusion.
AB  - Interstitial exclusion, defined as the fraction of interstitial fluid volume
      inaccessible to a solute, was evaluated for immunoglobulin G (IgG) in selected
      tissues of rats by a method previously applied to serum albumin (29). IgG
      distribution volumes were also measured for intestine. 125I-labeled rat IgG was
      infused for 5 or 7 days (n = 4 rats each) with an implanted osmotic pump (Alzet).
      At the termination of infusion, the rat was anesthetized, nephrectomized, and
      injected with 51Cr-labeled EDTA (4 h) to label total extracellular fluid volume
      and 131I-labeled bovine IgG (5 min) to label plasma volume. Samples of skin,
      muscle, and tendon were assayed for total and extractable tracer activity.
      Interstitial fluid from these tissues was sampled postmortem with nylon wicks for
      assay of 125I-labeled IgG and endogenous albumin and IgG. Exclusion of IgG was
      calculated from the difference between extravascular 125I-labeled IgG and 51Cr
      labeled EDTA distribution volumes. In contrast to our previous experience with
      tracer albumin, 125I-labeled IgG was not fully extractable from minced skin,
      muscle, or tendon by isotonic saline; only 71-83% was recovered under conditions
      that eluted 92-96% of tracer albumin and 94-99% of tracer EDTA. We conclude that
      approximately 20% of extravascular 125I-labeled IgG in these tissues is
      sequestered or bound in the interstitium. Calculation of IgG fractional exclusion
      from extractable tracer yielded the following values (means +/- SE, n = 8 rats):
      leg muscles 0.37 +/- 0.09, leg skin 0.44 +/- 0.03, back skin 0.36 +/- 0.04, tail
      skin 0.40 +/- 0.08, and tail tendon 0.55 +/- 0.04.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8304503
TI  - Ventricular interaction is described by three coupling coefficients.
AB  - Previous studies of ventricular interaction have quantified interaction by making
      small pressure or volume changes in one ventricle and measuring the resulting
      pressure or volume changes in the opposite ventricle. The ratios between the
      pressure and volume changes in opposite ventricles have been used as coupling
      coefficients or measures of ventricular interaction. This method of calculating
      coupling coefficients implicitly uses mathematical relationships that have useful
      features not generally appreciated. Starting from the definition of coupling
      coefficients we show that, without making any assumptions about ventricular
      interaction, all 24 possible coupling coefficients can be derived from a smaller
      set of four coupling coefficients. Furthermore, by making the single assumption
      that the ventricles behave elastically, we show that the set of four coefficients
      can be reduced to a set of three. Thus only three indexes are required to
      describe interaction, but these may vary with changes in ventricular volumes and
      pressures around which the indexes are measured. Furthermore, when comparisons
      between experimental studies are made, it is necessary to normalize the indexes
      with respect to ventricular volume.

PMID- 8304504
TI  - Baroreflex dysfunction in diabetes mellitus. I. Selective impairment of
      parasympathetic control of heart rate.
AB  - The purpose of this study was to determine the effect of diabetes mellitus on
      baroreflex control of heart rate. Diabetes (blood glucose = 378 +/- 21 mg/dl) was
      induced in rabbits by alloxan (n = 9). Alloxan-treated rabbits that remained
      normoglycemic (n = 9) and rabbits given saline instead of alloxan (n = 5) served
      as controls. Baroreflex control of heart rate was evaluated in conscious rabbits
      by measuring changes in heart rate during phenylephrine-induced increases and
      nitroglycerin-induced decreases in arterial pressure. In diabetic rabbits, the
      gain of the baroreflex-mediated bradycardia in response to increased pressure
      decreased significantly from -1.8 +/- 0.3 beats.min-1 x mmHg-1 before alloxan (n
      = 9) to -0.9 +/- 0.1 and -0.9 +/- 0.3 beats.min-1 x mmHg-1 after 12 and 24 wk of
      diabetes, respectively (n = 8; P < 0.05). There was no significant change in
      baroreflex gain in either alloxan-treated or saline-treated normoglycemic
      rabbits. Baroreflex-mediated bradycardia was not influenced significantly after
      beta-adrenergic blockade with propranolol (1 mg/kg) and was still impaired in
      diabetic vs. control rabbits after propranolol. The gain of the baroreflex
      mediated tachycardia in response to decreased pressure was not altered in any of
      the three groups. Propranolol significantly decreased but did not abolish
      baroreflex-mediated tachycardia. Neither the vagal nor the sympathetic component
      of the tachycardia was altered significantly by diabetes.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8304505
TI  - Baroreflex dysfunction in diabetes mellitus. II. Site of baroreflex impairment in
      diabetic rabbits.
AB  - In our companion paper [T. S. McDowell, M. W. Chapleau, G. Hajduczok, and F. M.
      Abboud, Am. J. Physiol. 266 (Heart Circ. Physiol. 35): H235-H243, 1994] we report
      that baroreflex-mediated bradycardia is impaired in diabetic rabbits. The purpose
      of the present study was to identify the site of impairment. Diabetes was induced
      in rabbits by alloxan (90-100 mg/kg iv; n = 7). Alloxan-treated rabbits that
      remained normoglycemic (n = 8) and rabbits given saline instead of alloxan (n =
      4) served as controls. Twenty-four weeks after administration of alloxan or
      saline, rabbits were anesthetized with alpha-chloralose. Aortic baroreceptor and
      renal sympathetic nerve activity (RSNA) were recorded during phenylephrine- and
      nitroglycerin-induced changes in arterial pressure. The slope of the baroreceptor
      pressure-activity relation was not significantly different in diabetic rabbits
      (1.3 +/- 0.3%/mmHg, n = 7) compared with either alloxan-treated (1.3 +/-
      0.1%/mmHg) or saline-treated normoglycemic rabbits (1.2 +/- 0.2%/mmHg). The slope
      of the arterial pressure-RSNA relation was not significantly different in
      diabetic rabbits (-3.5 +/- 0.3%/mmHg, n = 7) compared with the alloxan-treated
      normoglycemic rabbits (-3.0 +/- 0.4%/mmHg, n = 8) and was greater than that in
      saline-treated normoglycemic rabbits (-1.9 +/- 0.3%/mmHg, n = 4; P < 0.05). The
      decreases in heart rate in response to electrical stimulation (10 V, 2 ms, 0.5-16
      Hz) of the cut peripheral end of the right cervical vagus were similar in
      diabetic and alloxan-treated normoglycemic rabbits.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8304506
TI  - Circulatory and metabolic effects of anemia in hyperinsulinemic ovine fetuses.
AB  - Infants born to women with poorly controlled diabetes mellitus have an increased
      incidence of perinatal asphyxia, cardiovascular abnormalities, elevated
      catecholamines, and sudden fetal death. Although hyperinsulinemic fetuses of
      diabetic women often exhibit polycythemia, they may also develop anemia because
      of pregnancy- and/or delivery-related complications. Experimental fetal
      hyperinsulinemia results in cardiovascular changes and a surge in catecholamines.
      We hypothesized that reductions in fetal O2 availability via anemic hypoxia
      limits O2 transport and compromises the hemodynamically and metabolically
      stressed but compensated hyperinsulinemic fetus. Chronically catheterized fetuses
      receiving insulin (n = 9) or placebo (n = 5) for 48 h were rendered anemic by an
      isovolemic exchange transfusion. In the hyperinsulinemic state, anemic-hypoxia
      augmented the insulin-mediated surge in norepinephrine concentration and
      increases in blood flow to brain, heart, and adrenal glands. Insulin-related
      increase in the combined ventricular output was sustained during anemia. O2
      delivery to the fetus decreased, extraction increased, and O2 uptake did not
      change. Regional O2 delivery to the brain, kidney, gastrointestinal tract,
      muscle, fat, pancreas, spleen, and carcass decreased. Hyperinsulinemic ovine
      fetus exposed to anemic hypoxia demonstrated an accentuated surge in
      norepinephrine, a sustained increase in the combined ventricular output,
      preservation of systemic O2 uptake, and compromised regional O2 delivery to
      certain vascular regions. We conclude that the hyperinsulinemic fetus was able to
      compensate for anemic hypoxia by increased or sustained regional vascular
      perfusion.

PMID- 8304508
TI  - Dysfunction and safety factor strength-duration curves for biphasic defibrillator
      waveforms.
AB  - Newly developed biphasic waveforms significantly lower defibrillation threshold
      in animal and clinical models. However, underlying mechanisms and optimum
      waveform shape are unknown. Defibrillation shocks produce dysfunction; safety
      factor, the ratio of shock intensity inducing dysfunction to that producing
      stimulation of partially refractory cells, is an important parameter for
      defibrillator waveforms. We determined dysfunction and safety factor strength
      duration curves for symmetric and asymmetric (50% undershoot) monophasic and
      biphasic rectangular (0%-tilt) waveforms. Dysfunction threshold, defined as the
      voltage producing a 4-s postshock contractile arrest, was determined for
      waveforms with total durations from 1 to 40 ms. For all waveforms, dysfunction
      threshold decreased with waveform duration. At all durations, dysfunction
      threshold was similar for symmetric monophasic and biphasic waveforms with the
      same total duration. In contrast, asymmetric biphasic waveforms increased
      dysfunction threshold 14 +/- 3% (P < 0.005) compared with monophasic control
      waveforms. Because long-duration, low-tilt, biphasic waveforms improve excitation
      threshold for refractory cells, they should improve defibrillation threshold.
      Asymmetric waveforms have the additional advantage of improving safety factor by
      reducing postshock dysfunction.

PMID- 8304507
TI  - Moderate hyperglycemia affects ischemic brain ATP levels but not intracellular
      pH.
AB  - We used 31P nuclear magnetic resonance (NMR) spectroscopy to study the effect of
      moderate hyperglycemia on brain ATP and intracellular pH in a model of severe
      incomplete forebrain ischemia. Plasma glucose in the hyperglycemic rats was 277
      +/- 9 mg/100 ml compared with 115 +/- 10 mg/100 ml in the normoglycemic rats at
      the onset of ischemia. After 15 min of ischemia, brain ATP levels decreased to 31
      +/- 8% in normoglycemic rats vs. 63 +/- 11% in hyperglycemic rats (P < 0.05).
      Phosphocreatine levels were 31 +/- 9 and 55 +/- 8% for normoglycemic and
      hyperglycemic rats, respectively. Intracellular pH decreased to the same level
      (approximately 6.5) in both normoglycemic and hyperglycemic animals after 15 min
      of ischemia. In summary, we found that moderate hyperglycemia during severe
      incomplete forebrain ischemia significantly increases ischemic brain ATP levels
      but does not have a significant effect on intracellular pH. These results support
      the hypothesis that alterations in brain ATP and adenosine concentrations may be
      important in the pathogenesis of ischemic tissue injury under moderate
      hyperglycemic conditions, whereas alterations in tissue pH may be less important.

PMID- 8304509
TI  - Does a general alteration in nitric oxide synthesis system occur in spontaneously
      hypertensive rats?
AB  - Immune dysfunction has been reported in spontaneously hypertensive rats (SHR).
      The current study investigated interactions between macrophages or vascular
      smooth muscle cells (VSMC) and lymphocytes in SHR and examined the role of nitric
      oxide (NO) in this interaction. SHR macrophages significantly inhibited the
      proliferation of lymphocytes from SHR and the genetic control, Wistar-Kyoto rats
      (WKY). This inhibition was reversed by a NO synthase inhibitor, NG-monomethyl-L
      arginine (L-NMMA). SHR VSMC also significantly inhibited the proliferation
      responses of lymphocytes from SHR and WKY. The inhibition was cell density
      dependent. In addition, L-NMMA fully reversed the inhibition by SHR VSMC. Upon
      stimulation, the macrophages and VSMC from SHR produced a significantly higher
      amount of NO compared with those from WKY. These results suggest that the
      overproduction of NO was involved in the interaction between macrophages or VSMC
      and lymphocytes in SHR. Increased NO synthase activity in macrophages and VSMC
      may indicate a general activation of the NO synthesis system in SHR. The
      alteration of the NO synthesis system may be an important factor contributing to
      the lymphocyte depression in hypertension.

PMID- 8304510
TI  - Sulfhydryl compounds, captopril, and MPG inhibit complement-mediated myocardial
      injury.
AB  - Factors including complement activation, neutrophil infiltration, and oxygen
      derived free radicals have been implicated in the pathogenesis of myocardial
      tissue injury during ischemia and reperfusion. Certain sulfhydryl-containing
      compounds have been shown to inhibit complement activation. The sulfhydryl
      compounds captopril and N-(2-mercaptopropionyl)-glycine (MPG) are antioxidant
      compounds that previously have been shown to protect the myocardium from ischemia
      and reperfusion-induced damage. In this study, captopril (an angiotensin
      converting-enzyme inhibitor; ACEI) and MPG, and the non-sulfhydryl compound
      enalaprilat (also an ACEI) were tested for their ability to protect the isolated
      perfused rabbit heart against complement-induced injury. Both captopril and MPG
      protected hearts against complement-mediated increases in left ventricular end
      diastolic pressure and increases in coronary arterial perfusion pressure in a
      concentration-dependent manner, whereas enalaprilat was not protective. The
      ability of these compounds to inhibit complement activation also was tested using
      an in vitro complement-mediated red blood cell hemolysis assay. These findings
      offer additional insight as to the mechanism whereby captopril, MPG, and possibly
      other sulfhydryl compounds, may be acting to provide cytoprotection during
      myocardial ischemia and reperfusion.

PMID- 8304511
TI  - Interactions of nitroglycerin and sulfhydryl-donating compounds in coronary
      microvessels.
AB  - Previous studies have shown the effect of nitroglycerin on coronary microvessels
      < 100 microns in diameter is markedly enhanced by L-cysteine. These studies were
      performed to examine the mechanisms responsible for this effect. Under control
      conditions, nitroglycerin caused potent dilations of large (> 200 microns diam)
      coronary microvessels while having minimal effects on small (< 100 microns diam)
      coronary microvessels [peak relaxations 85 +/- 4 vs. 23 +/- 3% (mean +/- SE) of
      endothelin-1-constricted vessels, respectively]. L-Cysteine (100 microM) and N
      acetylcysteine (100 microM) markedly enhanced nitroglycerin-induced relaxations
      of small coronary microvessels (peak relaxation 84 +/- 6 and 87 +/- 12%,
      respectively) while having no effect on relaxations of vessels > 100 microns. In
      contrast, neither L-methionine (100 microM) nor glutathione (100 microM) enhanced
      nitroglycerin's vasodilation of small coronary microvessels. The effects of L
      cysteine and N-acetylcysteine on the augmentation of nitroglycerin vasodilatation
      in smaller coronary microvessels was abolished in the presence of buthionine
      sulfoximine (100 microM), a potent inhibitor of intracellular glutathione
      synthesis. Buthionine sulfoximine had no effect on the vasodilatation produced by
      nitroprusside. These data demonstrate that, in smaller coronary microvessels, L
      cysteine and N-acetylcysteine enhance nitroglycerin-induced vasodilatation by
      increasing intracellular glutathione concentrations. Intracellular glutathione,
      formed from either L-cysteine or N-acetylcysteine, may participate in the
      formation of an intermediate of nitroglycerin biotransformation or may maintain a
      redox potential within coronary microvessels that favors enzymatic bioconversion
      of nitroglycerin.

PMID- 8304513
TI  - Pressure-flow characteristics of the coronary collaterals: a model study.
AB  - The pressure-flow relationship of the coronary collaterals is investigated by
      using an electrical analog model that combines the coronary epicardial arteries
      with the nonlinear characteristics of the intramyocardial circulation. The study
      aims to examine some controversial issues concerning the collateral circulation,
      including the transmural distribution of the collaterals, the distensibility of
      the collateral vessels (whether rigid or complaint), the effects of
      microcirculatory embolization, the collateral zero-flow pressure, and the
      nonlinearity of the collateral pressure-flow relationship. The study is carried
      out by simulating and comparing two basic experimental set-ups in which a
      coronary artery is ligated and the retrograde flow serves as an index of
      collateral flow. In the first "free-flow" setup, flow is allowed to bleed
      retrogradely against atmospheric pressure while perfusion pressure to the rest of
      the coronary arteries is varied over a wide range. In the second "back-pressure"
      setup, the coronary perfusion pressure is maintained at the control levels while
      the back pressure to the retrograde flow in the excised artery is varied.
      According to the analysis, the nonlinear pressure-flow relationships depend
      heavily on the experimental setup and are a function of the distensibility of the
      collaterals, which are distributed mainly on the epicardial surface, and the
      nonlinear contraction characteristics of the myocardium. The measured retrograde
      flow tends to underestimate the total collateral flow for the back-pressure setup
      because of antegrade flow escape.

PMID- 8304512
TI  - Mathematical model of acetylcholine kinetics in neuroeffector junctions.
AB  - Acetylcholine (ACh) kinetics in neuroeffector junctions (NEJ) of the sinus node
      plays a key role in vagal control of heart rate. Prior studies have shown that
      the concentration of ACh ([ACh]) in NEJ appears to follow first-order linear
      kinetics. To find out the reason why, we examine mathematically diffusion,
      degradation, and receptor binding of ACh in NEJ. We identify seven conditions
      that potentially influence ACh kinetics. Because these conditions are satisfied
      for NEJ in the sinus node, 1) the nonlinearity of ACh binding to muscarinic
      receptors has little effect on [ACh]; 2) [ACh] does not depend on the
      distribution of acetylcholinesterase between the interstitial space and the
      pacemaker cells; 3) the interval from trough to subsequent peak [ACh] at the
      pacemaker cells is negligible; 4) the mean [ACh] at the pacemaker cells is
      proportional to the frequency of vagal activity multiplied by the amount of ACh
      released per vagal stimulus and divided by the rate coefficient of ACh
      degradation; and 5) [ACh] at pacemaker cells nearly follows first-order linear
      kinetics but does not at other sites in the NEJ. We conclude that earlier studies
      showed that [ACh] follows first-order linear kinetics, because they predicted
      [ACh] only at pacemaker cells. ACh kinetics at other sites in the NEJ, such as at
      nerve endings, is different.

PMID- 8304514
TI  - Mechanical equilibrium determines the fractal fiber architecture of aortic heart
      valve leaflets.
AB  - In this work, the structure of the aortic valve is derived from its function,
      which (in the closed-valve configuration) is to support a uniform pressure load.
      It is assumed that this load is transferred to the aortic wall by a one-parameter
      family of fibers under tension. The equation of equilibrium for this fiber
      structure turns out to be equivalent to the equation of motion of vortex lines in
      the self-induction approximation. The method of Buttke (J. Comput. Phys. 76:301
      326, 1988) is used to solve these equations and, hence, to determine the fiber
      architecture of the aortic leaflets. Because of a singularity at the center of
      the aortic valve, the computed fiber architecture has a fractal character with
      increasing complexity at progressively smaller scales. The computed fiber
      architecture resembles the branching braided structure of the collagen fibers
      that support the real aortic valve.

PMID- 8304515
TI  - Measurement of left ventricular volume in normal and volume-overloaded canine
      hearts.
AB  - Serial studies of adaptation to aortic regurgitation (AR) were undertaken to
      determine whether sonomicrometry and echocardiography could be combined to
      measure changes in left ventricular (LV) cavitary volume (Vlv) and wall mass
      using the geometric formula [Vlv = K pi b2 alpha--wall volume], where K is a
      constant depending on the geometric model and a and be are epicardial major- and
      minor-axis diameters, respectively. Postmortem studies were performed in six
      normal dogs and in nine with AR; ultrasonic ventricular dimensions were measured
      as Vlv was varied with an intracavitary balloon. Three models were tested: 1)
      ellipsoid (model I; K = 1/6), 2) cylinder-ellipsoid (model II; K = 5/24), and 3)
      cylinder (model III; K = 1/4). The slope of the relationship between calculated
      Vlv and balloon volume varied between models (I, 0.71 +/- 0.11; II, 0.89 +/-
      0.14; III, 1.07 +/- 0.17), and empiric determination of K to produce a slope of
      1.0 resulted in a value of 0.26 +/- 0.04, not significantly different from the
      cylindrical model. Serial measurements of LV dimensions in 10 chronically
      instrumented conscious dogs revealed no significant change in end-diastolic or
      end-ejection LV shape after up to 16 wk of AR. Sonomicrometry and
      echocardiography can be integrated using a cylindrical geometric model to
      accurately estimate changes in end-diastolic or end-ejection Vlv during chronic
      volume overload.

PMID- 8304516
TI  - Continual electric field stimulation preserves contractile function of adult
      ventricular myocytes in primary culture.
AB  - To model with greater fidelity the electromechanical function of freshly isolated
      heart muscle cells in primary culture, we describe a technique for the continual
      electrical stimulation of adult myocytes at physiological frequencies for several
      days. A reusable plastic cover was constructed to fit standard, disposable 175
      cm2 tissue culture flasks and to hold parallel graphite electrodes along the long
      axis of each flask, which treated a uniform electric field that resulted in a
      capture efficiency of ventricular myocytes of 75-80%. Computer-controlled
      amplifiers were designed to be capable of driving a number of flasks
      concurrently, each containing up to 4 x 10(6) myocytes, over a range of
      stimulation frequencies (from 0.1 to 7.0 Hz) with reversal of electrode polarity
      after each stimulus to prevent the development of pH gradients around each
      electrode. Unlike quiescent, unstimulated myocytes, the amplitude of contraction,
      and velocities of shortening and relaxation did not change in myocytes paced at 3
      5 Hz for up to 72 h. The maintenance of normal contractile function in paced
      myocytes required mechanical contraction per se, since paced myocytes that
      remained quiescent due to the inclusion of 2.5 microM verapamil in the culture
      medium for 48 h also exhibited a decline in contractility when paced after
      verapamil removal. Similarly, pacing increased peak calcium current compared with
      quiescent cells that had not been paced. Thus myocyte contraction at
      physiological frequencies induced by continual uniform electric field stimulation
      in short-term primary culture in defining medium maintains some biophysical
      parameters of myocyte phenotype that are similar to those observed in freshly
      isolated adult ventricular myocytes.

PMID- 8304517
TI  - Rat vascular tissues express all three alpha-isoforms of Na(+)-K(+)-ATPase.
AB  - The catalytic alpha- and smaller glycosylated beta-subunits of the membrane
      transport enzyme Na(+)-K(+)-adenosinetriphosphatase (ATPase) occur in different
      molecular forms, alpha 1, alpha 2, alpha 3, beta 1, and beta 2. The catalytic
      alpha 1-, alpha 2-, and alpha 3-subunits of the enzyme have varying affinities
      for digitalis and exist in different tissues with unique distribution patterns.
      In this report we document for the first time the existence of alpha 1-, alpha 2
      , alpha 3-subunit proteins (all approximately 97.5 kDa) in cultured rat aortic
      smooth muscle cells and rat tail arteries. In addition to the three molecular
      forms of the alpha-protein we detected a minor band at approximately 68-kDa
      position in aortic smooth muscle cells, which may correspond to the truncated
      alpha 1-protein reported earlier.

PMID- 8304518
TI  - Regional differences in LV collagen accumulation and mature cross-linking after
      myocardial infarction in rats.
AB  - To determine the extent of and any regional differences in remodeling response of
      the extracellular matrix (ECM) to myocardial infarction (MI), moderate-to-large
      transmural infarcts were surgically produced in left ventricular (LV) free wall
      of rats. Animals were killed 13 wk after surgery. In comparison to age-matched
      controls, infarction was associated with an overall increase in heart weight,
      which included hypertrophy of both the right ventricle and LV. Although the
      remaining viable myocardium in LV free wall was significantly reduced, the
      interventricular septum was hypertrophied some 30% compared with control tissues
      (247 +/- 9 vs. 189 +/- 8 mg). Collagen concentration more than doubled in
      remaining viable free wall (8.92 +/- 0.59 vs. 3.95 +/- 0.25 mg/100 mg, P <
      0.0001), and a smaller but still highly significant 27% increase occurred (P <
      0.01) in the more remote septum. Degree of covalent cross-linking of collagen
      fibrils as assessed by hydroxylysylpyridinoline (HP) concentration also revealed
      regional differences in response of the ECM to infarction. Although HP
      concentration was increased 60% in viable free wall (P < 0.05) post-MI, it was
      unchanged in the septum. With respect to collagen characteristics of the
      transmural infarct per se, the scar exhibited still further increases in both
      collagen and HP concentrations compared with the already elevated values for
      these two parameters in viable free wall. The results indicate that any
      evaluation of the remodeling response of viable myocardium post-MI must include
      not only the myocyte but also the ECM, the principal component of which is
      collagen.

PMID- 8304519
TI  - Transfer function analysis from arterial baroreceptor afferent activity to renal
      nerve activity in rabbits.
AB  - In vagotomized and anesthetized rabbits, aortic pressure (AP), aortic depressor
      nerve activity (ANA), and renal sympathetic nerve activity (RNA) were
      simultaneously measured while perturbing AP randomly. To quantitatively
      characterize the role of the arterial baroreflex system in generating RNA, we
      determined the transfer function (TF) of the central baroreflex arc from ANA to
      RNA in the frequency domain (0.02-5 Hz). The magnitude of squared coherence was >
      0.5, the phase was close to -180 degrees, and the gain of TF was flat over 0.02
      0.3 Hz, indicating that changes in RNA were linearly and instantaneously but
      inversely related to changes in ANA over this frequency range. Above 0.3 Hz, the
      coherence was low, suggesting that RNA unrelated to ANA existed in the frequency
      range. In animals without AP perturbations, power spectrum of RNA resided over
      0.2-5 Hz with a broad peak at 1 Hz, which may represent central activity. Our
      results suggest that over 0.02-0.3 Hz the relationship between arterial
      baroreceptor afferent nerve activity and RNA is linear and instantaneous but
      above 0.3 Hz it is not linear possibly due to an interaction between central
      activity and arterial baroreflex.

PMID- 8304520
TI  - Ouabain in plasma from spontaneously hypertensive rats.
AB  - Ouabain has recently been identified in mammalian plasma with an apparent
      adrenocortical origin. The objectives of the present study were to determine
      whether boiled plasma supernatants (BPS) from spontaneously hypertensive rats
      (SHR) contained elevated levels of material able to inhibit 86Rb uptake, an
      indicator of sodium pump activity, compared with Wistar-Kyoto rats (WKY).
      Furthermore, the effect of increasing dietary calcium content from 1 to 3% on
      86Rb-uptake inhibitory activity in plasma was examined. BPS from SHR and WKY
      consuming 1% calcium contained sodium pump inhibitory activity equivalent to
      16.43 +/- 0.23 and 5.08 +/- 0.10 ng ouabain/ml, respectively (P < 0.0001).
      Increasing dietary calcium intake to 3% reduced plasma ouabain-like activity
      (OLA) to 9.97 +/- 0.20 ng/ml (P < 0.0001) in SHR but was without effect in WKY
      (5.39 +/- 0.05; not significant). It was then determined whether the plasma 86Rb
      uptake inhibition could be attributed to authentic ouabain. In WKY plasma pools
      the percentage of OLA attributable to authentic ouabain was 38.0% by
      radioimmunoassay and 56.7% by 86Rb-uptake assay. In SHR these values were 3.8%
      and < 7.1%, respectively. Whereas the data in the present study provide
      confirmation of the presence of ouabain in rat plasma, ouabain does not account
      for the elevated OLA in SHR plasma reported here and elsewhere. This
      hypertensinogenic cardiotonic steroid appears to be appropriately downregulated
      in SHR rats.

PMID- 8304521
TI  - Chronic hypoxia is associated with reduced delayed rectifier K+ current in rat
      pulmonary artery muscle cells.
AB  - Pulmonary hypertension due to long-term hypoxia occurs as a result of both
      chronic obstructive pulmonary disease and habitation at high altitudes. Studies
      in animal models of chronic hypoxia have demonstrated the development of a
      persistent depolarization of pulmonary artery (PA) smooth muscle cells (SMCs). In
      seeking to explain this effect, we compared under normoxic conditions the K+
      currents in SMCs isolated from small PA of chronically hypoxic and normoxic rats.
      Chronic hypoxia was associated with a marked (40-50%) reduction in amplitude of a
      K+ current, which had the pharmacological and kinetic characteristics of a
      delayed rectifier. The resting potential of the isolated PA cells from
      chronically hypoxic animals was significantly more positive (-43.5 +/- 2 mV) than
      that of cells from normoxic animals (-54.3 +/- 2 mV), and this depolarization
      could be approximately mimicked in the cells from normoxic animals by application
      of 1 mM 4-aminopyridine, a blocker of the delayed rectifier K+ current.
      Glibenclamide (1 microM), a blocker of ATP-sensitive K+ (KATP) channels, also
      caused a substantial (14.5 +/- 2.2 mV) depolarization of the membrane. These
      results suggest that both delayed rectifier and ATP-dependent K+ currents
      contribute to setting the membrane potential in these cells and are consistent
      with the possibility that downregulation of the delayed rectifier K+ current
      contributes to the depolarization and altered responsiveness to vasoactive agents
      of PAs that occurs during long-term hypoxia.

PMID- 8304522
TI  - Effects of potassium channel blockers on basal vascular tone and reactive
      hyperemia of canine diaphragm.
AB  - Glibenclamide, iberiotoxin, and apamin (blockers of ATP-sensitive, large
      conductance, and small-conductance Ca(2+)-activated potassium channels,
      respectively) were infused into the diaphragmatic vasculature of anesthetized
      dogs to assess the contribution of these channels in the regulation of basal tone
      and the response to brief occlusions of the left phrenic artery (reactive
      hyperemia). Baseline phrenic flow (Qphr), peak postocclusive flow, and reactive
      hyperemia duration in response to 10-, 30-, 60-, and 120-s arterial occlusions
      were measured before (control) and after the infusion of K+ channel blockers in
      three groups of animals. Glibenclamide at 5 x 10(-6), 1 x 10(-5), and 8 x 10(-5)
      M increased baseline phrenic resistance to 140, 204, and 192% of control values,
      respectively. Peak postocclusive Qphr and duration of hyperemia in response to
      all occlusion durations were significantly attenuated after glibenclamide
      infusion. Iberiotoxin infusion at 1 x 10(-8), 3 x 10(-8), and 1 x 10(-7) M
      increased phrenic resistance to 141, 133, and 146% of control values,
      respectively. By comparison, baseline phrenic resistance rose to 159 and 145% of
      control in response to 1 x 10(-7) and 1 x 10(-6) M apamin, respectively.
      Iberiotoxin and apamin reduced peak postocclusive flow and duration of hyperemia
      only in response to 10- and 30-s occlusions. We infused K+ channel blockers along
      with lemakalim into the diaphragm during constant flow perfusion in separate
      groups of animals. When infused alone, lemakalim reduced phrenic resistance by 60
      70%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304523
TI  - Role of endogenous ANG II on resetting arterial baroreflex during development.
AB  - Angiotensin II (ANG II) has been shown in adults to modulate baroreflex responses
      in heart rate (HR) and sympathetic outflow. To test the hypothesis that high
      circulating levels of ANG II in the newborn period contribute to the resetting of
      the arterial baroreflex observed postnatally, we studied baroreflex-mediated
      changes in HR and renal sympathetic nerve activity (RSNA) before and after
      angiotensin-converting enzyme (ACE) inhibition in fetal and newborn sheep. In the
      newborn, administration of the ACE inhibitor enalaprilat produced significant (P
      < 0.05) decreases in baseline RSNA (69 +/- 5 vs. 47 +/- 7% maximum) and HR (81 +/
      3 vs. 59 +/- 4% max), as well as in the baroreflex curve midpoints for RSNA (93
      +/- 4 vs. 87 +/- 3 mmHg) and HR (95 +/- 4 vs. 81 +/- 5 mmHg); no change in the
      sensitivities (gains) of the baroreflex responses were seen. In contrast, no
      significant changes in baseline RSNA, HR, baroreflex curve midpoint, or
      sensitivity were demonstrated in the fetus. Infusion of ANG II in newborn lambs
      reversed the effects of ACE inhibition on the baroreflex responses. Additional
      experiments evaluating the effects of ACE inhibition in vagotomized newborns
      again showed resetting of the baroreflex, demonstrating that vagally mediated
      mechanisms are not involved in regulating the changes in sympathetic outflow
      during the neonatal period. These results suggest that endogenous ANG II
      contributes to the resetting of the baroreflex observed postnatally.

PMID- 8304524
TI  - Tumor necrosis factor-alpha increases myocardial microvascular transport in vivo.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a primary mediator in the pathogenesis
      of tissue injury, and high circulating levels of TNF-alpha are found in a variety
      of pathological conditions. In open-chest anesthetized dogs, the effects of
      intracoronary recombinant human TNF-alpha (rTNF-alpha; 100 ng/kg for 60 min) on
      myocardial microvascular transport of a small hydrophilic indicator was examined
      by the single-injection, residue-detection method. Intracoronary infusion of rTNF
      alpha increased myocardial microvascular transport after 120 min. This increase
      was preceded by a sustained decline in cardiac output and was associated with the
      appearance of areas with myocardial necrosis in the regional left ventricular
      wall. The myocardial plasma flow rate and maximum plasma flow rate in response to
      a 30-s coronary occlusion were not influenced by rTNF-alpha, although a decrease
      in the myocardial plasma flow rate was observed after 180 min. Circulating
      neutrophil counts were increased by rTNF-alpha, but the increase in myocardial
      capillary permeability could not be ascribed to regional neutrophil infiltration.
      We conclude that picomolar levels of rTNF-alpha can influence the movement of
      small hydrophilic molecules across the myocardial microvascular barrier in vivo
      and induce a prolonged decrease in cardiac performance. These effects may be
      important elements in myocardial pathophysiology.

PMID- 8304525
TI  - Role of sarcoplasmic reticulum in loss of load-sensitive relaxation in pressure
      overload cardiac hypertrophy.
AB  - The loss of load-sensitive relaxation observed in the pressure-overloaded heart
      may reflect a strategy of slowed cytosolic Ca2+ uptake to yield a prolongation of
      the active state of the muscle and a decrease in cellular energy expenditure. A
      decrease in the potential of the sarcoplasmic reticulum (SR) to resequester
      cytosolic Ca2+ during diastole could contribute to this attenuated load
      sensitivity. To test this hypothesis, both in vitro mechanical function of
      anterior papillary muscles and the SR Ca2+ sequestration potential of female
      guinea pig left ventricle were compared in cardiac hypertrophy (Hyp) and sham
      operated (Sham) groups. Twenty-one days of pressure overload induced by
      coarctation of the suprarenal, subdiaphragmatic aorta resulted in a 36% increase
      in left ventricular mass in the Hyp. Peak isometric tension, the rate of
      isometric tension development, and the maximal rates of isometric and isotonic
      relaxation were significantly reduced in Hyp. Load-sensitive relaxation were
      significantly reduced in Hyp. Load-sensitive relaxation quantified by the ratio
      of a rapid loading to unloading force step in isotonically contracting papillary
      muscle was reduced 50% in Hyp muscles. Maximum activity of SR Ca(2+)
      adenosinetriphosphatase (ATPase) measured under optimal conditions (37 degrees C;
      saturating Ca2+) was unaltered, but at low free Ca2+ concentrations (0.65
      microM), it was decreased by 43% of the Sham response. Bivariate regression
      analysis revealed a significant (r = 0.84; P = 0.009) relationship between the
      decrease in SR Ca(2+)-ATPase activity and the loss of load-sensitive relaxation
      after aortic coarctation. Stimulation of the SR Ca(2+)-ATPase by the catalytic
      subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase resulted
      in a 2.6-fold increase for Sham but only a 1.6-fold increase for Hyp.
      Semiquantitative Western blot radioimmunoassays revealed that the changes in SR
      Ca(2+)-ATPase activity were not due to decreases in the content of the Ca(2+)
      ATPase protein or phospholamban. Our data directly implicate a role for decreased
      SR function in attenuated load sensitivity. A purposeful downregulation of SR
      Ca2+ uptake likely results from a qualitative rather than a quantitative change
      in the ATPase and possibly one of its key regulators, phospholamban.

PMID- 8304526
TI  - Modulation of sympathetic nerve activity during posthandgrip muscle ischemia in
      humans.
AB  - To evaluate modulation of muscle sympathetic nerve activity (MSNA) during
      posthandgrip muscle ischemia (PHGMI), subjects performed 2 min of isometric
      handgrip at 33% of maximal voluntary contraction (MVC) followed by 2 min of PHGMI
      produced by forearm vascular occlusion. The response to PHGMI was studied in the
      absence and again during the addition of contralateral rhythmic handgrip (RHG; 40
      times/min) at 15% (n = 6) and 30% (n = 10) MVC during the second minute of the
      PHGMI. Additionally, to isolate the effect of central command, response to PHGMI
      was studied during attempted RHG after sensory nerve blockade (n = 5). RHG for 2
      min at 15 and 30% MVC and attempted RHG for 2 min did not increase MSNA.
      Isometric handgrip elicited an 130 +/- 48% increase in MSNA (P < 0.05), which was
      maintained during PHGMI. RHG at 15 and 30% MVC elicited an attenuation of MSNA (
      10 +/- 7% and -14 +/- 6%, respectively) when performed during the second minute
      of PHGMI (P < 0.05). In contrast, attempted RHG did not significantly affect MSNA
      during PHGMI. The findings demonstrate modulation of MSNA during activation of
      the muscle metaboreflex. The attenuation of metaboreceptor-mediated increases in
      MSNA appear to be the result of mechanosensitive muscle afferents and not central
      command.

PMID- 8304527
TI  - Peptidases modulate bradykinin-induced arteriolar dilation in the hamster cheek
      pouch.
AB  - The purpose of this study was to investigate whether angiotensin-converting
      enzyme (ACE; EC 3.4.15.1) and neutral endopeptidase (NEP; EC 3.4.24.11), two
      membrane-bound metalloenzymes that are widely distributed in the peripheral
      microcirculation and degrade kinins very effectively, modulate bradykinin-induced
      arteriolar dilation in vivo. Using intravital microscopy, we measured diameter of
      second-order arterioles in the hamster cheek pouch during suffusion of bradykinin
      (0.1-10.0 microM) before and after topical application of captopril (10.0 microM)
      and phosphoramidon (10.0 nM). We found that each inhibitor significantly
      potentiated bradykinin-induced increase in arteriolar diameter (P < 0.05).
      Suffusion of other proteinase inhibitors (excluding ACE and NEP inhibitors) had
      no significant effect on bradykinin-induced responses. Captopril and
      phosphoramidon did not potentiate isoproterenol (0.1 microM)-induced arteriolar
      dilation in the cheek pouch. Collectively, these data indicate that ACE and NEP
      each plays an important role in regulating bradykinin-induced vasorelaxation in
      the peripheral microcirculation in vivo.

PMID- 8304528
TI  - L-NAME antagonizes vasopressin V2-induced vasodilatation in dogs.
AB  - Experiments were performed in conscious chronically instrumented dogs to study
      the mechanism of hemodynamic effects mediated by selective vasopressin V2
      agonists. In one group of dogs (n = 5) instrumented for the measurement of
      arterial pressure and cardiac output (electromagnetic flowmeter), the infusion of
      NG-nitro-L-arginine methyl ester (L-NAME; 20 or 40 micrograms.kg-1 x min-1)
      prevented or significantly inhibited the increase in cardiac output, heart rate
      and systemic conductance induced by injections of 1-desamino-8-D-arginine
      vasopressin (DDAVP, desmopressin) and 4-valine-8-D-arginine vasopressin (VDAVP),
      two selective V2 agonists. L-NAME infusion did not modify the aortic adenosine
      3',5'-cyclic monophosphate increase induced by DDAVP infusion. In a second group
      of dogs similarly prepared (n = 4), the administration of L-arginine (10 mg.kg-1
      x min-1) at the same time as that of L-NAME (20 micrograms.kg-1 x min-1)
      completely prevented the hemodynamic effects of L-NAME and restored the response
      to DDAVP administration. In a third group of dogs (n = 4), the infusion of a
      bradykinin B2 antagonist, at a rate that significantly inhibited the cardiac
      output, heart rate, and blood pressure responses to bradykinin, did not modify
      the hemodynamic response to DDAVP infusion. We conclude that the hemodynamic
      effects of selective V2 agonists in dogs are not mediated by bradykinin release
      but instead via a V2-like receptor on endothelial cells that triggers the release
      of nitric oxide.

PMID- 8304529
TI  - Hypothermia to endotoxin involves reduced thermogenesis, macrophage-dependent
      mechanisms, and prostaglandins.
AB  - At a subthermoneutral ambient temperature of 24 degrees C, intravenous
      administration of bacterial endotoxin (lipopolysaccharide, LPS) to rats resulted
      in hypothermia associated with a fall in oxygen consumption followed by fever. At
      the thermoneutral ambient temperature of 30 degrees C, animals only responded to
      LPS with fever. The hypothermia and reduction in oxygen consumption were
      attenuated in rats with eliminated peripheral macrophages. By contrast,
      macrophage elimination did not affect the febrile response to LPS. Both the
      hypothermia and the febrile response to LPS were prevented by peripheral
      administration of the cyclooxygenase inhibitor indomethacin. We conclude that
      hypothermia in response to LPS is caused by reduced thermogenesis, involves
      antipyretic products released from peripheral macrophages, and is mediated by
      prostaglandins. In addition, the febrile response likewise involves
      prostaglandins, but in contrast to the hypothermia appears to be independent of
      pyrogens released from peripheral macrophages. Previously, we reported the
      induction of the pyrogen interleukin-1 in the brain during the time course of the
      febrile response to LPS (34). The latter observations support the hypothesis that
      the second phase of biphasic fever is mediated by synthesis and action of
      pyrogens inside the blood-brain barrier.

PMID- 8304530
TI  - Roles of skeletal muscle morphology and activity in determining Na(+)-K(+)-ATPase
      concentration in young pigs.
AB  - It has been demonstrated previously that the Na(+)-K(+)-adenosinetriphosphatase
      (Na(+)-K(+)-ATPase) concentration (total concentration of [3H]ouabain-binding
      sites = maximal [3H]ouabain-binding capacity, Bmax) in longissimus dorsi muscle
      is higher in young pigs living in a cold than in a warm environment, with the
      effect being even greater in those on a low rather than a high energy intake in
      the cold. The importance of thyroid status, myofiber type and size, and muscular
      activity in determining the concentration of Na(+)-K(+)-ATPase has therefore been
      assessed in longissimus dorsi, semitendinosus, and soleus muscles from 8-wk-old
      littermate pigs, which had been living 35 or 10 degrees C on either a high or a
      low energy intake for 3-4 wk. Changes in neither plasma thyroid hormone
      concentrations nor myofiber type could account for the greater Bmax at 10 vs. 35
      degrees C observed in all three muscles; instead, it was possibly related to the
      greater muscular activity associated with shivering in the cold. More than 50% of
      the increase in Bmax on the low compared with the high intake in the cold could
      be attributed to the smaller fiber size and hence greater membrane area in
      animals on the low intake, and it is concluded that membrane surface area must be
      assessed in studies of membrane-bound enzymes.

PMID- 8304531
TI  - Hepatic phosphate trapping, decreased ATP, and increased feeding after 2,5
      anhydro-D-mannitol.
AB  - The mechanism by which the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM)
      elicits feeding behavior was investigated by studying its metabolism and
      biochemical effects in liver. Thin-layer chromatography of liver extracts from
      rats given 2,5-AM containing 14C-labeled 2,5-AM showed that the analogue is
      phosphorylated in vivo with a time course that parallels the eating response. In
      vivo 31P nuclear magnetic resonance spectroscopy of rat liver during intravenous
      infusion of 2,5-AM and high-resolution nuclear magnetic resonance analyses of
      liver extracts showed that 2,5-AM is rapidly phosphorylated in liver, trapping
      hepatic phosphate and decreasing ATP, inorganic phosphate, and phosphate
      diesters. These changes occurred in a time frame in which the feeding response is
      elicited in conscious animals given the same dose of 2,5-AM by the same route.
      During an interval in which 2,5-AM increased eating, it also increased urinary
      uric acid excretion, implicating enhanced adenosine degradation in the reduction
      in hepatic ATP. These results provide the first direct evidence that changes in a
      high-energy phosphate-carrying compound in liver may provide a signal to initiate
      eating behavior.

PMID- 8304532
TI  - Factors associated with vasopressin release in exercising swine.
AB  - This study examined the effect of dynamic exercise on vasopressin release in the
      miniswine and factors that may elicit this response (n = 15). Thus lysine
      vasopressin (LVP), the catecholamines epinephrine and norepinephrine (EPI and
      NE), plasma renin activity (PRA), and plasma volume, Na+, and osmolality were
      measured before and during treadmill running at work intensities of 60, 80, and
      100% of each swine's maximal heart rate reserve (HRR). LVP increased in a
      progressive manner similar to that of humans, ranging from 5.9 +/- 0.4 pg/ml
      before exercise to 30.1 +/- 4.5 pg/ml during maximal exercise. EPI, NE, and PRA
      [an index of angiotensin II (ANG II) activity] demonstrated a pattern of response
      comparable to LVP. Although these hormones can influence the release of LVP, only
      PRA displayed a strong correlation with LVP (r = 0.84). When ANG II synthesis was
      blocked (captopril, 1-3 mg/kg, intra-atrial injection) during exercise (80% HRR),
      plasma LVP was reduced from 9.9 +/- 0.6 to 7.5 +/- 0.6 pg/ml (P < 0.05). In
      addition, moderate-to-strong correlations were found between plasma
      concentrations of LVP and plasma osmolality (r = 0.79) and body temperature (r =
      0.78). Plasma LVP also correlated with decreases in plasma volume (r = 0.84).
      These data suggest that the miniswine model is a good one for studying
      vasopressin effects during exercise and that ANG II appears to be a particularly
      strong stimulus for the release of this hormone.

PMID- 8304533
TI  - Lipopolysaccharide induces fever and depresses locomotor activity in unrestrained
      mice.
AB  - The purpose of this study was to characterize the basic biology of fever to
      lipopolysaccharide (LPS) in unrestrained mice. Although LPS has been shown to
      induce fevers in many laboratory animals (e.g., rats, guinea pigs, rabbits),
      there is some question of whether LPS causes a fall or rise in body temperature
      (Tb) in mice. Tb was measured by biotelemetry in unrestrained mice maintained at
      an ambient temperature of 30 degrees C. Intraperitoneal injections of LPS at
      doses of 1.0, 2.5, and 3.0 mg/kg induced dose-independent prompt decreases of Tb
      for 5.7 h. After this postinjection reduction, Tb increased and reached a peak at
      approximately 24 h postinjection. The peak rises in Tb were dose dependent.
      Changes in Tb due to LPS were accompanied by suppression of locomotor activity.
      Indomethacin, at a dose that did not affect normal Tb, enhanced the temperature
      lowering effect of LPS as well as inhibited the febrile rise of Tb after LPS.
      Indomethacin did not modify the reduction in activity caused by the injections of
      LPS. Food intake of the mice was decreased by LPS in a dose-dependent manner, and
      tolerance developed to a second injection of LPS. We conclude that freely moving
      mice can develop pronounced and reproducible fevers in response to LPS, which is
      different in time course, dose-dependent profile, induction of pyrogenic
      tolerance profile, and mode of inhibition by indomethacin from those responses
      that have been observed in other species studied so far.

PMID- 8304534
TI  - Pontine cholinergic reticular mechanisms cause state-dependent changes in the
      discharge of parabrachial neurons.
AB  - The present study examined the hypothesis that cholinoceptive reticular
      mechanisms in the gigantocellular tegmental field (FTG) of the medial pontine
      reticular formation cause state-dependent changes in the discharge of
      parabrachial neurons. In chronically implanted, unanesthetized cats,
      extracellular recordings were made from nonrespiratory and respiratory neurons in
      the parabrachial nuclear complex (PBNC) during the natural sleep-wake cycle and
      during the rapid eye movement (REM) sleeplike state caused by FTG microinjection
      of carbachol or neostigmine. PBNC cells that increased discharge during natural
      REM sleep (REM-on cells) revealed similar increased discharge during the
      carbachol-induced REM sleeplike state (DCarb). Cells that decreased discharge in
      natural REM sleep (REM-off cells) displayed decreased discharge during both DCarb
      and the neostigmine-induced REM sleeplike states. The limited sample of
      parabrachial respiratory neurons revealed significantly diminished discharge
      during the cholinergically induced REM sleeplike state. Thus cholinoceptive
      mechanisms localized to specific regions of the pontine reticular formation can
      cause state-dependent changes in the firing rates of respiratory and
      nonrespiratory neurons in the PBNC.

PMID- 8304535
TI  - Increased venous PCO2 enhances dynamic responses of avian intrapulmonary
      chemoreceptors.
AB  - We quantified the neural discharge of intrapulmonary chemoreceptors (IPC)
      innervating the left lungs of anesthetized Pekin ducks. Right and left lungs were
      separately unidirectionally ventilated. Alternating steps in CO2 concentration (0
      6%, 11-s period) were delivered to the left lung under control conditions [mixed
      venous PCO2, (PVCO2) 43 +/- 4 Torr] and under venous CO2 load conditions (PVCO2
      79 +/- 6 Torr). During venous CO2 loading the right lung was ventilated with 10
      20% CO2, while the left lung was ventilated with a sufficient flow of gas
      containing 0% CO2 to maintain normal expired PCO2 (indicated by constant IPC
      discharge rate). Venous loading increased the peak-to-peak amplitude of the
      oscillation in IPC discharge by 4.3 +/- 1.8 s-1 (n = 11, P < 0.05), left lung
      ventilation was increased 2.6-fold, and the IPC step response became more prompt.
      The mean IPC discharge rate during the CO2 stepping cycle was not significantly
      affected (11.8 +/- 1.4 during control vs. 10.3 +/- 1.3 s-1 during venous
      loading). Increased IPC discharge oscillations were due to enhancement of the
      dynamic overshoot in receptor discharge after the 6-0% downstep in inspired CO2
      and to a depression of discharge during 6% inspired CO2. We propose that the
      phasic enhancement of IPC discharge oscillations during venous CO2 loading may
      cause feedback inhibition of ventilatory drive.

PMID- 8304536
TI  - Inhibition of nitric oxide synthesis suppresses sleep in rabbits.
AB  - The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of
      nitric oxide synthesis, on spontaneous and interleukin-1 (IL-1)-induced sleep
      were examined in rabbits. Animals were injected intracerebroventricularly or
      intravenously during the light phase with vehicle, L-NAME, IL-1, or the
      combination of L-NAME and IL-1. Injection of L-NAME (5 mg icv and 100 mg/kg iv)
      suppressed both non-rapid eye movement sleep (NREMS) and rapid eye movement sleep
      (REMS) for 4-6 h. The sleep-suppressive effects are unlikely due to pressor
      responses to L-NAME because administration of L-NAME (5 mg icv) produced only a
      transient (3-4 min) slight increase in systemic blood pressure. Injection of IL-1
      (20 ng icv) elicited fever, suppressed REMS, and increased NREMS for 6 h. NREMS
      was suppressed for 3 h after the combined intracerebroventricular injections of 5
      mg L-NAME and 20 ng IL-1 and was elevated during postinjection hours 4-6.
      Administration of IL-1 (30 ng/kg iv) increased NREMS and brain temperature for 2
      h. After the combined injection of IL-1 and L-NAME (100 mg/kg), NREMS was
      significantly suppressed during postinjection hours 1-5. It is not known whether
      the interactions between the sleep-suppressive effects of L-NAME and the NREMS
      promoting effects of IL-1 are specific, being mediated via a common mechanism, or
      whether they are additive, being mediated via independent mechanisms. The
      pyrogenic and REMS-suppressive actions of either intracerebroventricularly or
      intravenously injected IL-1 were not affected by L-NAME.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8304537
TI  - Role of excitatory amino acids in regulation of rat pial microvasculature.
AB  - Recently, attention has been drawn to the possibility that excitatory amino acids
      (EAAs) may play an important role in the pathogenesis of hypoxic-ischemic
      neuronal injury. Exaggerated release of EAAs and excessive stimulation of N
      methyl-D-aspartate (NMDA) receptors and other EAA receptors have been suggested
      to contribute to neuronal death in ischemia and anoxia. A number of in vitro and
      in vivo experimental studies have shown that EAA-receptor antagonists exert a
      protective effect on the brain after cerebral ischemia. Because neurons are in
      close apposition to small intracerebral vessels, synaptically released EAAs might
      also regulate small blood vessel function. With the use of quantitative
      television microscopic observations, in vivo studies were undertaken on pial
      arterioles of rats. Perivascular administration of cumulative doses (10(-7)-10(
      2) M) of L-glycine, L-glutamate, L-aspartate, and NMDA on the pial microvessels
      resulted in concentration-dependent constriction of pial arterioles (5-30%
      decreases in diameter) and cerebrovasospasm; the relative order of potency was
      aspartate > NMDA > glycine > glutamate. High concentrations of EAAs often
      resulted in rupture of postcapillary venules. No amine or opiate antagonist or
      cyclooxygenase inhibitor prevented or attenuated the effects of these putative
      EAAs. EAA-induced constriction and spasm of pial arterioles as well as rupture of
      venules could, however, be blocked by the noncompetitive NMDA-receptor antagonist
      MK-801 and by Mg2+. MK-801 also produced a concentration-dependent relaxation on
      normal pial arterioles. These results are compatible with the idea that a
      specific NMDA-receptor complex (RC) exists in rat cortical microvessels, which
      subserves vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304538
TI  - Validation in sheep of the doubly labeled water method for estimating CO2
      production.
AB  - Carbon dioxide production (rCO2) was estimated in four sheep over a period of 10
      days using doubly labeled water (2H and 18O) and was compared with simultaneous
      respiration chamber measurements of CO2. The excess 2H and 18O measurements were
      corrected for the empirically determined effects of isotope rebreathing within
      the confines of the chambers. A weighted monoexponential curve was then fitted to
      the data from which isotope flux rates and ultimately rCO2 and water turnover
      (rH2O) estimates were made. The curve fits were weighted assuming a Poisson
      model. Selection of this weighting policy did not bias the results, and curvature
      in the data also appeared to have little effect on the rCO2 estimates.
      Fractionated evaporative water loss expressed as a fraction of rH2O (X) was
      estimated from water balance and breath water production estimates; the mean X
      was 0.145 and ranged from 0.108 to 0.183. Corrections for 2H loss in fecal solids
      reduced the mean rH2O (4,746 g/day) by 35.5 g/day and increased the mean rCO2
      (332.3 l/day) by 21.2 l/day. Further corrections to account for 2H loss in
      methane (mean production rate 27.2 l/day) reduced rH2O by 33.8 g/day and
      increased rCO2 by 20.3 l/day. The final isotopic estimates of rH2O were 14.6 +/-
      6.59% (n = 4) lower than direct measurements and the mean rCO2 was 3.5 +/- 14.48%
      (n = 4) lower than the chamber measured rCO2. However, in one of the animals
      studied the rCO2 deviated markedly from the chamber-derived value, and this
      discrepancy has yet to be explained. When this animal was excluded from the
      comparisons, the standard deviation was greatly reduced (+/- 3.6, n = 3) and the
      mean overall error on rCO2 was +3.6%.

PMID- 8304539
TI  - Corticotropin responses to hypoglycemia and hypotension during ovine pregnancy.
AB  - The adrenocorticotropic hormone (ACTH) responses to hypoglycemia and to
      hypotension were compared in pregnant and nonpregnant ewes. In the first study
      pregnant and nonpregnant ewes were each subjected to hypoglycemia induced by
      injection of 0.05, 0.10, or 0.25 U regular insulin/kg body wt or to saline
      infused as a control. In the second study pregnant and nonpregnant ewes were
      subjected to hypotension induced by the infusion of 2.5, 5.0, or 10.0 micrograms
      nitroprusside.kg-1.min-1 or to dextrose infused as a control. ACTH responses to
      hypoglycemia were significantly increased in the pregnant ewes, and the relation
      between plasma glucose and plasma ACTH was shifted to the right, indicating
      greater ACTH responses for a given level of hypoglycemia in the pregnant state.
      The mean ACTH response to infusion of nitroprusside was reduced during pregnancy,
      despite significantly lower mean arterial blood pressure in the pregnant ewes.
      When the relation between mean arterial pressure and ACTH was compared in the two
      groups of ewes, the relation was significantly shifted to the left in the
      pregnant ewes, indicating lower ACTH responses to a given level of pressure
      during pregnancy. The results suggest that pregnancy does not uniformly alter
      ACTH responses to stimuli, suggesting multiple, stimulus-specific effects of
      pregnancy on the hypothalamo-pituitary-adrenal axis.

PMID- 8304540
TI  - Vasopressin response to hyperosmolality and hypotension during ovine pregnancy.
AB  - The arginine vasopressin (AVP) responses to hyperosmolality and to hypotension
      were compared in pregnant and nonpregnant ewes. When the responses to infusion of
      normal or hypertonic saline were compared, plasma AVP and Na+ concentrations were
      lower in pregnant ewes than nonpregnant ewes, but the relation between plasma AVP
      and Na+ concentrations was not altered in the pregnant state. In a second study
      the AVP response to hypotension, induced by the infusion of 2.5, 5.0, or 10.0
      micrograms nitroprusside.kg-1.min-1, was compared in pregnant and nonpregnant
      ewes. Despite significantly lower mean arterial blood pressures in the pregnant
      ewes, the mean plasma AVP concentration after infusion of nitroprusside was not
      increased during pregnancy. Therefore, the relation between mean arterial
      pressure and AVP was significantly shifted to the left in the pregnant ewes,
      indicating lower AVP concentrations for a given level of arterial pressure during
      pregnancy. The results suggest that pregnancy alters the regulation of AVP by
      arterial pressure but does not affect the regulation of AVP by plasma sodium
      concentration in the ewe.

PMID- 8304541
TI  - ANF-C-receptor-mediated inhibition of aortic smooth muscle cell proliferation and
      thymidine kinase activity.
AB  - We have investigated the inhibition of DNA synthesis and cell proliferation by
      rat atrial natriuretic factor [rANF-(99-126)] and several synthetic peptides that
      bind selectively to the ANF-C-type clearance receptors in subcultured aortic
      smooth muscle cells. These peptides decreased serum-induced 1) [3H]thymidine
      incorporation, 2) cell proliferation, and 3) thymidine kinase activity without
      altering basal or elevated cAMP or cGMP levels. In contrast, another ANF-C
      receptor-binding peptide, des[Gln116,Ser117,Gly118,Leu119,Gly120] rANF-(102-121)
      NH2 (cANF), failed to decrease serum-induced mitogenesis, yet 100 nM cANF
      reversed the inhibition of DNA synthesis and cell proliferation and the decrease
      of thymidine kinase activity elicited by other C receptor-binding peptides,
      including rANF-(99-126), rANF-(103-125), and porcine C-type natriuretic peptide
      [pCNP-(1-22)]. Delayed addition experiments indicated that atrial peptides
      influence a relatively late event (or events) during the G1 phase of the cell
      cycle. The inhibition of DNA synthesis by C-receptor-binding atrial peptides
      appeared to be selective for aortic smooth muscle cells, inasmuch as a potent
      inhibitory agonist peptide, Cys116-rANF-(102-116), was without significant
      influence on the incorporation of thymidine in cultured rat mesangial cells or
      bovine pulmonary artery endothelial cells. These results indicate that atrial
      natriuretic peptide analogues decrease vascular smooth muscle cell mitogenesis
      and proliferation by a cyclic nucleotide-independent mechanism involving the C
      type receptor. Moreover the inhibition of DNA synthesis by rANF-(99-126) and the
      neuropeptide pCNP-(1-22) appears to be mediated by the ANF-C-type receptor and is
      associated with inhibition of thymidine kinase activity.

PMID- 8304542
TI  - Calcium channel antagonists prevent urinary bladder growth and neuroplasticity
      following mechanical stress.
AB  - Cytosolic Ca2+ has been postulated to regulate smooth muscle hypertrophy and
      growth factor production. Consistent with this hypothesis we report that the Ca2+
      channel antagonists verapamil and diltiazem prevent bladder and neuronal growth
      in rats in response to 3 wk of urethral obstruction. Ca2+ channel blockers
      prevented 30-45% of the increase in bladder weight, protein, and DNA content
      found in obstructed animals. Similarly, these drugs produced a 15-27% reduction
      in area profiles for retrogradely labeled (Fluoro-Gold) motoneurons in the major
      pelvic ganglia and afferents in the L6-S1 dorsal root ganglia after obstruction.
      The reduced growth in neuronal areas was attributed, in part, to less nerve
      growth factor (NGF) in bladders of obstructed rats receiving verapamil (8.5
      pg/bladder) or diltiazem (14.5 pg/bladder) compared with obstructed animals not
      given these drugs (58.2 pg/bladder). The alpha 1-adrenergic antagonist, prazosin,
      while decreasing voiding frequency in obstructed rats, had no significant impact
      on bladder weight or neuronal size. These reductions in the increase in bladder
      hypertrophy and NGF content may be due to altered handling of Ca2+.

PMID- 8304543
TI  - Spontaneous waves of cerebral blood flow associated with a pattern of
      electrocortical activity.
AB  - We examined the relationship between spontaneous changes in regional cerebral
      blood flow and electrocortical (ECoG) activity in spinalized rats anesthetized
      with 1.5% isoflurane. Regional cerebral blood flow, measured by laser-Doppler
      flowmetry, and ECoG activity were measured bilaterally in frontal and parietal
      cortex. Spontaneous cerebrovascular waves (SCWs) were seen in all (n = 80) rats
      and consisted of sawtoothed waves with an average amplitude of 20.1 +/- 0.78%, a
      duration of 11.7 +/- 0.6 s, and a frequency of 6.3 +/- 0.2 min-1. SCWs were
      always preceded by a high-amplitude burst of ECoG activity (averaging 752.0 +/-
      41.8 microV at 5.6 +/- 0.2 Hz) and comparable to the well-recognized burst
      suppression/barbiturate-spindle patterns of ECoG activity. The latency between
      bursts and SCWs averaged 1.71 +/- 0.05 s. The frequency of bursts and SCWs was
      highly correlated within and between cortical areas bilaterally (r > 0.9) and
      appeared synchronously across brain. Deepening anesthesia (to 1.75% isoflurane)
      reduced the frequency of bursts and SCWs by > 30% but not their correlation (r >
      0.9) and minimally increased burst-SCW latency. SCWs differed from an uncommon
      sinusoidal oscillation regional cerebral blood flow triggered by changes in
      arterial pressure and independent of the ECoG. Bursts and SCWs were not affected
      by inhibition of nitric oxide synthase. The results indicate that a population of
      local cortical neurons, probably driven from subcortical pacemakers, when
      excited, elicits local cerebrovascular vasodilation.

PMID- 8304544
TI  - Adenosine mediates hypoxic release of arginine vasopressin in fetal sheep.
AB  - The effects of adenosine on plasma arginine vasopressin (AVP) concentrations were
      determined in chronically catheterized fetal sheep (> 0.8 term). Infusion of
      adenosine [0.35 +/- 0.01 (SE) mg.min-1.kg-1] into the inferior vena cava of six
      fetuses caused a transient fall in arterial PO2 (by approximately 3 Torr), a
      slight reduction in arterial pH, and a 5- to 6-mmHg decrease in diastolic
      pressure without significantly affecting systolic or mean arterial values. A
      lower rate of infusion (0.19 +/- 0.01 mg.min-1 x kg-1) in five fetuses had
      virtually no effect on arterial blood gases, pH, or arterial pressures. Both the
      low- and high-dose adenosine infusions significantly increased fetal plasma AVP
      concentrations (1.7 +/- 0.2 to 25 +/- 7 pg/ml and 1.6 +/- 0.1 to 54 +/- 8 pg/ml,
      respectively). Intravenous infusion of papaverine lowered fetal diastolic and
      mean arterial pressures by approximately 8 mmHg but had no significant effect on
      plasma levels of AVP. During an hour of isocapnic hypoxia (arterial PO2 12-13
      Torr), fetal plasma AVP levels increased from 1.7 +/- 0.2 to 40 +/- 6 pg/ml.
      Intra-arterial infusion of the adenosine receptor antagonist 8-(p-sulfophenyl)
      theophylline significantly blunted the hypoxia-induced rise in plasma AVP
      concentrations to a maximum mean level of 11 +/- 6 pg/ml. These results indicate
      that 1) adenosine causes a dose-dependent increase in plasma AVP concentrations
      and 2) a hypoxia-induced rise in fetal adenosine levels triggers vasopressin
      release.

PMID- 8304545
TI  - Modulation of rate at which serotonin-induced contraction decays in guinea pig
      trachea.
AB  - Stimulation of the type 2 serotonin (5-HT2) receptor in guinea pig trachea with 5
      HT results in a contraction that decays in the continued presence of 5-HT. The
      decay of the 5-HT contraction has been proposed to be dependent on 5-HT2 receptor
      activation and to reflect desensitization of the receptor. The characteristics of
      the decay of the 5-HT contraction may also be dependent on other properties of
      the tissue. The effects of modulation of biochemical pathways implicated in
      airway smooth muscle contraction on the 5-HT contraction in isolated guinea pig
      trachea were determined with the use of a kinetic approach we developed
      previously. Decay of the 5-HT contraction was inhibited by cooling, increased by
      forskolin, 3-isobutylmethyl-1-xanthine, and 8-bromoadenosine 3',5'-cyclic
      monophosphate, and unaffected by staurosporine, H-7, H-8, phorbol 12,13
      dibutyrate, and by inhibitors of the three major pathways of arachidonic
      metabolism. The results suggest that decay of the 5-HT contraction in guinea pig
      trachea is dependent on both the receptor and the biochemical state of the
      tissue.

PMID- 8304546
TI  - Pontine reticular neurons provide tonic excitation to neurons in rostral
      ventrolateral medulla in rats.
AB  - To determine whether the pontine reticular formation (PRF) is a source of tonic
      activity for cardiovascular neurons in the rostral ventrolateral medulla (RVLM),
      the discharge of PRF neurons was inhibited by unilateral microinjections of
      glycine (1.0 M; 60 nl) while recording the discharge of single neurons in the
      RVLM in 14 Saffan-anesthetized rats. RVLM units were characterized as
      cardiovascular if their spontaneous activity was changed by baroreceptor
      activation and was synchronized to the cardiac cycle. Glycine injection into the
      ipsilateral PRF eliminated the ongoing activity of six cardiovascular units and
      reduced the activity of four (mean decrease -91 +/- 4%). Inhibition of these
      units lasted 20-115 s (mean 59 +/- 9 s). Glycine injection into the PRF had no
      effect on the discharge of five cardiovascular units. Activity of six
      noncardiovascular units did not respond to PRF blockade. Glycine injection into
      the PRF caused decreases in arterial pressure (-28 +/- 5 mmHg), heart rate (-23
      +/- 3 beats/min), and renal nerve activity (-42 +/- 7%) that also returned to
      control values between 25 and 120 s (mean 55 +/- 5 s). These results indicate
      that PRF neurons provide tonic excitatory drive to some cardiovascular neurons
      located in the RVLM.

PMID- 8304548
TI  - Processing of splanchnic and somatic input in thoracic spinal cord of the rat.
AB  - To better understand the spinal transmission of visceral afferent information, we
      conducted neurophysiological studies of single spinal neurons that receive input
      from the greater splanchnic nerve (GSN). Extracellular single-neuron recordings
      were made in the thoracic spinal cord of chloralose-anesthetized, paralyzed, and
      artificially ventilated rats, some of which had undergone acute spinal
      transection at C1. Neurons were divided into four classes according to their
      responses to GSN stimulation: one-burst excitatory, two-burst excitatory,
      biphasic, and inhibited. We then studied the characteristics of the convergent
      somatic input to each class of neurons using either natural somatic stimuli or
      electrical stimulation of the iliohypogastric nerve (IHN). Most splanchnic input
      was mediated by unmyelinated fibers, whereas somatic input was mediated by both
      unmyelinated and small myelinated fibers. Most of the neurons exhibited somatic
      receptive fields, and the majority responded to both innocuous and noxious
      somatic stimuli. However, a small number could be excited only by GSN
      stimulation. Although a careful analysis of response characteristics indicated
      that there was a tendency for neurons to exhibit similar responses to electrical
      stimulation of the GSN and the IHN, we observed many combinations of somatic and
      visceral responses. We suggest that visceral afferent activity, in addition to
      being processed via convergent somatovisceral pathways, may be processed by
      neurons that convey only visceral information or by neurons in which visceral and
      somatic information is differentially coded.

PMID- 8304547
TI  - Hypoxia selectively excites vasomotor neurons of rostral ventrolateral medulla in
      rats.
AB  - Systemic hypoxia [PaO2 27.3 +/- 1.8 (SE) mmHg] in anesthetized paralyzed rats
      reversibly increased within seconds the arterial pressure and activities of the
      sympathetic nerves and the reticulospinal vasomotor neurons of the rostral
      ventrolateral medulla (RVL). After peripheral chemodenervation, hypoxia also
      increased activity of the sympathetic nerves and doubled discharges of the
      vasomotor neurons while inhibiting a majority of the RVL respiratory neurons.
      Systemic hypercapnia was not effective in eliciting sympathoexcitatory responses.
      Iontophoresis of sodium cyanide stimulated the vasomotor and inhibited the
      respiratory neurons. In contrast, iontophoreses of H+, HCO3-, and lactate were
      without effects on activity of the vasomotor neurons. We conclude 1) hypoxia
      excites the vasomotor neurons by activating the arterial chemoreceptors and by
      activating intrinsic cellular mechanisms probably unrelated to accumulation of
      metabolic byproducts; 2) hypoxia may be the adequate stimulus exciting the RVL
      spinal vasomotor and inhibiting the respiratory neurons during the cerebral
      ischemic response; and 3) these vasomotor neurons may be central oxygen
      detectors.

PMID- 8304549
TI  - Splanchnic and somatic afferent convergence on cervical spinal neurons of the
      rat.
AB  - The rostral cervical spinal cord is increasingly being considered the source of
      important propriospinal regulation. To better understand the substrate for this
      function, we investigated the effects of stimulation of the greater splanchnic
      nerve (GSN) and both thoracic and cervical somatic afferents on the activity of
      cervical spinal neurons. Extracellular single-neuron recordings were made in the
      C2-C5 spinal segments of chloralose-anesthetized, paralyzed, and artificially
      ventilated rats. Neurons were classified according to their responses to GSN
      stimulation. Neurons were inhibited by this stimulation as frequently as they
      were excited. We then studied the characteristics of cervical and thoracic
      convergent somatic input to each class of neurons. Although all cervical neurons
      that responded to GSN stimulation responded to electrical stimulation of the
      iliohypogastric nerve (IHN), only the few neurons that exhibited whole body
      receptive fields (RF) responded to natural thoracic somatic stimuli. Responses to
      electrical stimulation of the GSN and IHN were similar for most neurons; most
      exhibited nociceptive cutaneous RFs in cervical dermatomes. These data indicate
      that input from cervical somatic afferents and from both thoracic visceral and
      thoracic somatic afferents converge on individual splanchnic-receptive cervical
      neurons. Although these neurons exhibited the predicted cervical somatic RFs,
      responses from thoracic levels did not exhibit discrete RFs, requiring instead
      more synchronous or more spatially convergent input.

PMID- 8304550
TI  - Reflex regulation of renal nerve activity in cardiac failure.
AB  - Efferent renal sympathetic nerve activity (ERSNA) is increased in the rat with
      low-cardiac-output congestive heart failure (CHF; myocardial infarction).
      Arterial and cardiopulmonary baroreflex control of ERSNA in CHF and control rats
      was examined. Cardiac index and arterial pressure were lower and total peripheral
      resistance index, left ventricular end-diastolic pressure, and heart-to-body
      weight ratio were higher in CHF than in control rats. Increases in left
      ventricular end diastolic pressure produced by intravenous volume loading failed
      to increase cardiac index in CHF rats as it did in control rats. Single-unit
      analysis of aortic baroreceptor nerve activity showed that CHF rats had higher
      pressure threshold, lower frequency at pressure threshold, and lower gain than
      control rats. Arterial baroreflex control of ERSNA was attenuated; this was due
      to diminished gain of the afferent limb while the gain of the central portion of
      the reflex was normal. Single-unit analysis of vagal nerve activity showed that
      CHF rats had higher pressure threshold, lower frequency at saturation, and lower
      gain than control rats. Cardiopulmonary baroreflex control of ERSNA was
      attenuated; this was due to diminished gain of the afferent limb while the gain
      of the central portion of the reflex was normal. In the CHF rat, arterial and
      cardiopulmonary baroreflex control of ERSNA is markedly attenuated because of
      abnormalities in the periphery at the level of the aortic and cardiopulmonary
      receptors, respectively, and not in the central nervous system.

PMID- 8304551
TI  - Identification and characterization of CCK-B/gastrin receptors in human
      pancreatic cancer cell lines.
AB  - The gastrointestinal peptide cholecystokinin (CCK) is known to stimulate growth
      of human pancreatic cancer in a receptor-mediated fashion. The purpose of this
      study was to characterize the receptor responsible for the trophic effects of CCK
      in cancer cells. With the use of homogenates of PANC-1 human pancreatic cancer
      cells grown in vitro, the binding characteristics and optimal conditions of
      radiolabeled selective CCK-receptor antagonists ([3H]L-365,260 and [3H]L-364,718)
      were examined. Specific and saturable binding was detected with [3H]L-365,260,
      and Scatchard analysis revealed that the data were consistent for a single site
      of binding with a binding affinity of 4.3 +/- 0.6 nM and a binding capacity
      (Bmax) of 283 +/- 68 fmol/mg protein in log phase cells. Binding was dependent on
      protein concentration, time, temperature, and pH and was sensitive to Na+, K+,
      Mg2+, and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid.
      In contrast to log phase cells, Bmax decreased by 80 and 92% in confluent and
      postconfluent cultures, respectively. Subcellular fractionation studies revealed
      that binding was in the membrane fraction. Competition experiments indicated that
      L-365,260 and gastrin were more effective at displacing the radiolabeled L
      365,260 than CCK. No binding was detected with the CCK-A antagonist [3H]L
      364,718. Assays performed with [3H]L-365,260 on five additional human pancreatic
      cancer cell lines in vitro and tumor tissue from xenografts in nude mice also
      revealed specific and saturable binding. These results provide the first
      identification of a CCK-B/gastrin receptor in human pancreatic cancer cells and
      tumors and explain the effects of CCK on the growth of this malignancy.

PMID- 8304552
TI  - Serotonin contracts the isolated rat pylorus via a 5-HT2-like receptor.
AB  - Serotonin (5-HT) produced concentration-dependent contractions of the isolated
      rat pylorus in vitro. Serotonergic contractions were antagonized by the calcium L
      channel blocker, diltiazem, but not by tetrodotoxin or atropine. Three drugs that
      block 5-HT2 receptors, ketanserin, xylamidine, and methysergide, unsurmountably
      inhibited contractions to 5-HT. In contrast, antagonists of 5-HT3, 5-HT1A/1B,
      beta-adrenergic, or alpha 1-adrenergic receptors did not alter the response to 5
      HT. Devazepide, an antagonist of cholecystokinin (CCK) type-A receptors, blocked
      contraction produced by CCK-8 but not by 5-HT. Conversely, the 5-HT2 antagonists
      did not affect CCK-stimulated contraction. These results suggest that 5-HT
      contracts the pylorus by a 5-HT2-like receptor on muscle and that this response
      occurs independently of CCKergic receptor mechanisms. Furthermore, the parallel
      between the overall pharmacological profile for serotonergic contraction of the
      pylorus and that observed previously for the anorectic action of peripheral 5-HT
      makes the pylorus a logical candidate for peripheral serotonergic control of
      feeding.

PMID- 8304553
TI  - High-flow microinfusion: tissue penetration and pharmacodynamics.
AB  - High-flow microinfusion provides a means for delivering macromolecules to large
      volumes of brain in easily obtainable time intervals. Slowly degraded
      approximately 180-kDa macromolecules, delivered at a constant volumetric flow
      rate of 3 microliters/min into homogeneous brain tissue (e.g., gray matter),
      would penetrate to a 1.5-cm radius in 12 h. The predicted concentration profile
      is relatively flat until it declines precipitously at the flow front. Hence,
      tissues are dosed rather uniformly, providing control over the undesired toxicity
      that may occur with alternative methods that depend on large concentration
      gradients for tissue transport. The penetration advantage of high-flow
      (convective) over low-flow (diffusive) microinfusion has been assessed at fixed
      pharmacodynamic effect. A 12-h high-flow microinfusion of a macromolecule
      degraded with a characteristic time of 33.5 h would provide 5- to 10-fold
      increases in volume over low-flow infusion and total treatment volumes > 10 cm3.
      Slower degradation rates would result in larger treatment volumes; more rapid
      degradation rates would reduce the volume but still favor convective over
      diffusive administration. This technique may be applicable to a variety of
      diagnostic and therapeutic agents such as radioimmunoconjugates, immunotoxins,
      enzymes, growth factors, and oligonucleotides.

PMID- 8304555
TI  - What does changing the temperature do to the melatonin rhythm in cultured chick
      pineal cells?
AB  - Chick pineal cells in static culture display a persistent, photosensitive
      circadian rhythm of melatonin production and release. We previously described the
      effects of light, the major physiological regulator of circadian rhythms, on the
      amplitude, period, and phase of the melatonin rhythm. Here we describe the
      effects of temperature, another physiological regulator of circadian rhythms, on
      the amplitude, period, and phase of this rhythm. Maintaining cells at 40.0-43.3
      degrees C (104-110 degrees F) instead of 36.7 degrees C (98 degrees F) doubled
      the amplitude of the melatonin rhythm. In contrast, amplitude was reduced by
      about half at 33.3 degrees C (92 degrees F), and at 46.7 degrees C (116 degrees
      F) melatonin production was stopped within a few hours. Although temperatures of
      40.0-43.3 degrees C raised melatonin output (unlike light, which suppresses it),
      they lengthened the period of the rhythm (as does constant light). Exposure of
      cells to 8-h pulses of these temperatures (40.0-43.3 degrees C) induced both
      phase delays and phase advances of the rhythm in subsequent cycles, with a phase
      dependence similar to that for the phase shifts induced by light pulses. Pulses
      of 40.0-43.3 degrees C were, however, weaker in their phase-shifting effects than
      light pulses. Pulses at still higher temperatures (46.7 degrees C) markedly
      inhibited melatonin output and delayed or disrupted the rhythm. The relationships
      (physiological and mechanistic) between the effects of temperature and light on
      the melatonin rhythm remain to be determined.

PMID- 8304554
TI  - Nitric oxide actions in paraventricular nucleus: cardiovascular and neurochemical
      implications.
AB  - We have examined potential functions of nitric oxide (NO) within the
      paraventricular nucleus (PVN) in urethan-anesthetized male Sprague-Dawley rats.
      Initial experiments demonstrated microinjection of 50 pmol of the NO donor,
      sodium nitroprusside (SNP), directly into the PVN resulted in significant
      decreases in mean blood pressure (BP) (-3,312 +/- 1,189 mmHg/s over 300-s
      response time; P < 0.05). To determine whether such effects were attributable to
      SNP-induced NO release, NO was administered into PVN directly by bilateral
      microdialysis of NO-containing artificial cerebrospinal fluid (NO-aCSF), a
      process that results in delivery of approximately 50 pmol NO.PVN-1 x min-1. Such
      microdialysis resulted in significant decreases in BP (-5,121 +/- 817 mmHg/s over
      1,200-s response time; P < 0.005), while aCSF microdialysis was without effect
      (1,298 +/- 1,071 mmHg/s over 1,200-s response time; P > 0.1). Amino acid
      concentrations were measured in dialysates collected during perfusion of the same
      PVN sites with either aCSF or NO-aCSF by high-performance liquid chromatography
      (HPLC) analysis. NO-aCSF induced significant increases in aspartate (aCSF 31 +/-
      7 pmol/30 min; NO-aCSF 134 +/- 33 pmol/30 min; P < 0.05), glutamate (aCSF 36 +/-
      5 pmol/30 min; NO-aCSF 417 +/- 108 pmol/30 min; P < 0.02), gamma-aminobutyric
      acid (aCSF 4.1 +/- 0.7 pmol/30 min; NO-aCSF 104 +/- 29 pmol/30 min; P < 0.02),
      and taurine (aCSF 34 +/- 3 pmol/30 min; NO-aCSF 117 +/- 24 pmol/30 min; P < 0.01)
      concentrations, while alanine, glutamine, and serine concentrations were
      unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304556
TI  - Weight loss in rats following intraventricular transplants of pancreatic islets.
AB  - Because of the body's resistance to permanent weight change, obesity remains a
      major health problem in modern society. It is hypothesized that the regulatory
      system defending body weight utilizes pancreatic insulin as an indicator of
      adiposity to the brain. To take advantage of this negative feedback system, we
      transplanted neonatal (experiment 1) or adult (experiment 2) pancreatic islets
      containing insulin-secreting cells into the 3rd ventricle of syngeneic Lewis
      rats. This resulted in an elevation of the insulin signal within the brain and a
      significant long-term reduction of body weight. Changes in food intake were
      consistent with the changes of body weight. The implantation of more islets
      resulted in a greater reduction of body weight, and changes in weight were
      inversely correlated with the level of insulin achieved in the cerebrospinal
      fluid. After the two studies were completed, histological examination revealed
      the presence of insulin-containing cells within the 3rd ventricle and adjacent
      hypothalamus. These studies suggest that transplanted insulin-secreting cells may
      provide a potential therapeutic strategy for maintenance of weight loss.

PMID- 8304557
TI  - Band 3 modulation and hypotonic-stimulated taurine efflux in skate erythrocytes.
AB  - Previous studies have shown that exposure of skate erythrocytes to hypotonic
      medium or isosmotic medium with permeant solutes such as ethylene glycol or
      ammonium chloride increases cell volume. Initial swelling is followed by a
      regulatory volume decrease accomplished by efflux of cell solutes, including the
      beta-amino acid taurine. Taurine efflux, as well as the cell volume recovery, is
      inhibited by stilbene disulfonates and other anion exchange inhibitors,
      suggesting involvement of the erythrocyte anion exchanger band 3. In the present
      study we show that binding of the stilbene dihydro 4,4'-diisothiocyanostilbene
      2,2'-disulfonic acid (H2DIDS) to intact cells doubles after exposure to one-half
      hypotonic medium. Binding also increases after exposure of erythrocytes to medium
      of one-third hypotonic medium and ethylene glycol medium, but DIDS binding is not
      significantly elevated in ammonium chloride medium. To investigate possible
      mechanisms for modulation of band 3, cells were labeled with 32PO4 and levels of
      protein phosphorylation determined. Phosphorylation of three proteins of
      molecular masses of 99, 65, and 32 kDa increases with hypotonic stress. Because
      the anion exchanger migrates with molecular mass near 100 kDa, the anion
      exchanger was immunoprecipitated. Hypotonic stress induces a rapid and persistent
      increase in the 32PO4 phosphorylation of the exchanger. This modification may be
      responsible for the increased DIDS binding and could be related to stimulated
      taurine efflux.

PMID- 8304558
TI  - Chronic stress affects immunologic but not cardiovascular responsiveness to acute
      psychological stress in humans.
AB  - This study deals with the effect of chronic stress on physiological
      responsiveness to an acute psychological stressor in male high school teachers.
      Chronic stress was operationalized as the self-reported number of everyday
      problems. Twenty-seven subjects reporting extremely low or high numbers of
      everyday problems were exposed to an acute psychological stressor, and changes in
      immunologic, endocrine, and cardiovascular parameters were monitored. The
      stressor included a learning process followed by a teaching session in which a
      confederate to the researchers was involved. Twenty subjects served as controls.
      The stressor had no effect on the endocrine variables measured but induced
      increases in heart rate and blood pressure, which were similar in both chronic
      stress groups. Analysis of subsets of blood lymphocytes revealed differences in
      natural killer (NK) and T cell responses in the low and the high stress groups.
      It is concluded that 1) immunologic responsiveness to an acute psychological
      stressor is related to problems experienced in daily life, and that 2) chronic
      stress differentially modifies the sensitivity of biological systems to mild
      acute stressors.

PMID- 8304559
TI  - Exchange of purines in human liver and skeletal muscle with short-term exhaustive
      exercise.
AB  - The exchange of purines in liver and active skeletal muscle with short-term
      exhaustive exercise was investigated. Eight male subjects performed two similar
      10-min bouts of exhaustive supine cycling, separated by 75 min of rest.
      Immediately after termination of the second bout, a tourniquet was applied to the
      upper part of the thigh for 10 min. After the first bout, the arterial
      concentration of hypoxanthine and uric acid increased from 4.1 +/- 0.3 (SE) to a
      peak value of 36.3 +/- 7.9 mumol/l (P < 0.05) and from 335 +/- 23 to a peak value
      of 421 +/- 28 mumol/l (P < 0.05), respectively. There was a net release of
      hypoxanthine from the muscle at 12 and 45 min postexercise and an uptake of
      hypoxanthine and inosine in the liver at 7 and 42 min postexercise. Uric acid was
      released from the liver at 7 and 42 min after exercise. Before the second
      exercise bout and at 2 and 10 min after the release of the tourniquet, there was
      a significant net uptake of uric acid by the muscle. The present study
      demonstrates that, after strenuous short-term exercise, the main source of plasma
      hypoxanthine is the muscle, with no net contribution of this purine from the
      liver. Hypoxanthine in the blood is taken up by the liver where most of it is
      converted to uric acid. After exercise and a short period of ischemia, uric acid
      is taken up by the muscle.

PMID- 8304560
TI  - Hypothermia to endotoxin involves the cytokine tumor necrosis factor and the
      neuropeptide vasopressin in rats.
AB  - Previously, we have reported that intravenous administration of bacterial
      endotoxin (lipopolysaccharide, LPS) in rats kept at a subthermoneutral ambient
      temperature of 24 degrees C results in a fall in colonic temperature that
      involved the release of antipyretic products by peripheral macrophages. Here, we
      demonstrate that treatment of rats with a biologically active antiserum to tumor
      necrosis factor (TNF) markedly attenuates the hypothermia in response to
      administration of LPS (0.5 mg/kg). Moreover, this hypothermia was prevented by
      central injection of a selective antagonist of V1 vasopressin receptors,
      dPTyr(Me) arginine vasopressin (AVP; 2 micrograms icv). AVP is thought to act as
      an antipyretic in the ventral septal area (VSA) of the brain. Because the AVP
      content of this area has been shown to be eliminated after long-term castration,
      we have tested the hypothesis that castration would attenuate the hypothermia in
      response to administration of LPS. Castrated rats displayed a markedly less
      hypothermic response than age-matched controls in response to administration of
      LPS. We conclude that hypothermia in response to intravenous injection of LPS
      involves the release of TNF from peripheral macrophages. Moreover, our results
      are consistent with the possibility that androgen-dependent vasopressinergic
      neurons in the VSA are mediating the hypothermia in response to intravenous
      administration of LPS.

PMID- 8304562
TI  - In memoriam Paul Chester Beaver, Ph.D. ASTMH member, 1944-1993.

PMID- 8304563
TI  - "Targeted research": an oxymoron that needs to be discussed.

PMID- 8304561
TI  - High-fat diet reduces glucose transporter responses to both insulin and exercise.
AB  - High-fat diet (HFD) induces skeletal muscle insulin resistance. To investigate
      associated changes in the plasma membrane glucose transporter, male Sprague
      Dawley rats were fed either chow [high-carbohydrate diet (HCD)] or HFD for 3 wk.
      Plasma membrane vesicles were prepared from hindlimb muscle of control, insulin
      stimulated (Ins), and acutely exercised (Ex) rats. Maximal vesicle glucose
      transport activity (Vmax) increased threefold with Ins and Ex treatment compared
      with controls in HCD rats; in HFD rats, increases were less than twofold.
      Transporter numbers (measured by cytochalasin B binding, CB) approximately
      doubled with Ins and Ex in both diet groups. Intrinsic activity (carrier
      turnover, Vmax/CB) increased significantly with stimulation in HCD but not HFD
      rats. Therefore, vesicles from HFD rats showed resistance to both exercise and
      insulin stimulation of muscle glucose transport. Transporter number increased
      normally, but intrinsic activity in HFD rats did not respond. Two conclusions are
      discussed: 1) translocation and activation are distinct, separable steps in
      transporter stimulation and 2) HFD produces effects that resemble the insulin
      resistance of starvation.

PMID- 8304564
TI  - In vivo sensitivity of Plasmodium falciparum to halofantrine hydrochloride in
      Burkina Faso.
AB  - Plasmodium falciparum susceptibility to halofantrine hydrochloride was
      investigated in a small village near Ouagadougou, Burkina Faso, where the
      parasite was known to be chloroquine resistant. An in vivo test was carried out
      in July 1992 at the beginning of the rainy season in children ranging in age from
      two to eight years with P. falciparum monospecific infections, asexual
      parasitemia greater than 800/microliters of blood, and a negative result on a
      Bergqvist urine test for 4-aminoquinolines. Among 206 children screened, 74 were
      selected for study. Blood samples were collected on days 0, 2, 4, 7 and 14, and
      100 microscopic fields of thick and thin blood smears were examined for parasite
      density and species identification. Halofantrine hydrochloride was administered
      under supervision at the standard dose of 24 mg/kg as 8 mg/kg given three times
      at 6-hr intervals with an observation period of 1 hr after each 8-mg/kg dose.
      Parasitemias cleared in all 74 cases by day 7, but there was a recurrence of
      parasitemia in six subjects (8.1%) on day 14. A second course of therapy with
      halofantrine resulted in prompt clearance of parasitemias in all of these
      children. The drug was well-tolerated and the hematologic and biochemical indices
      were not adversely affected by treatment.

PMID- 8304565
TI  - Successful treatment of Colombian cutaneous leishmaniasis with four injections of
      pentamidine.
AB  - We previously found that 2 mg of pentamidine isethionate/kg, administered every
      other day in seven injections, was 95% curative for Colombian cutaneous
      leishmaniasis. However, 17% of the patients had to prematurely terminate therapy
      due to drug toxicity and another 30% had mild-to-moderate toxic clinical
      reactions. In this report, we show that the same daily dose of drug, 2 mg/kg, but
      administered in only four every-other-day injections, resulted in an 84% cure
      rate in 38 patients. Twenty-one patients (55%) experienced side effects, three of
      which were moderate to severe. A higher daily dose of drug, 3 mg/kg, administered
      in four every-other-day injections, resulted in a 96% cure rate in 51 evaluable
      patients. Thirty-six of the treated patients (64%) experienced side effects, five
      of which were moderate to severe. Although hypotension and hypoglycemia were
      looked for in all patients, only one patient experienced hypoglycemia and it had
      normalized by follow-up. We propose that the regimen of 3 mg of pentamidine/kg
      every other day in four injections is optimal for Colombian cutaneous
      leishmaniasis and competitive with standard Glucantime therapy, in terms of cure
      rate, toxicity, length of time the patient has to be under medical supervision,
      and cost of drug plus medical attention. We suggest that such a short course of
      injectable agent be studied for the treatment of patients with cutaneous
      leishmaniasis from other endemic areas.

PMID- 8304566
TI  - Treatment of murine cryptosporidiosis with anticryptosporidial immune rat bile.
AB  - Persistent cryptosporidiosis was established in nu/nu BALB/c mice by oral
      inoculation with Cryptosporidium parvum oocysts. The model was used to determine
      the impact of anticryptosporidial immune rat bile on the resolution of the
      disease. Presence of C. parvum-specific IgA in the immune rat bile was determined
      by enzyme-linked immunosorbent assay. Infection of mice was verified by stool
      analysis for oocytes and by hematoxylin and eosin-stained intestinal sections
      from control mice (infected but untreated). Efficacy of treatment was determined
      in control and treated mice by analysis of identical, hematoxylin and eosin
      stained sections of the small intestine and cecum. Semi-quantitative comparisons
      were made by determining the percent of crypts infected with Cryptosporidium
      organisms. The scores of treated mice were significantly lower then controls.
      Microscopic analysis of intestinal sections showed less villus atrophy, crypt
      hyperplasia, and fewer organisms per crypt in the immune bile-treated mice than
      in controls. These results support a role for humoral immunity in the eradication
      of cryptosporidiosis.

PMID- 8304567
TI  - Enhanced larval cyst growth of Echinococcus multilocularis in praziquantel
      treated jirds (Meriones unguiculatus).
AB  - Jirds (Meriones unguiculatus) inoculated intraperitoneally with cystic material
      of Echinococcus multilocularis were given daily oral treatments of praziquantel
      at 300 mg/kg of body weight (bw) or dimethyl sulfoxide vehicle for five-day
      treatment regimens starting at 29 days postinoculation (PI) up to 69 days PI. At
      39 or 49 days PI, the growth of the larval cystic mass (LCM) in jirds following a
      single or two five-day treatment regimens was significantly enhanced (P < 0.05)
      by 129.0% (2.3-fold) or 102.9% (2.0-fold), respectively. At 59 or 69 days PI
      following three or four five-day treatments with praziquantel, LCM growth was
      enhanced by 47.8% (1.5-fold) and 44.1% (1.4-fold), respectively, but was no
      longer significantly different than that in control jirds. A single five-day
      treatment on 29-33 days PI (with necropsy at 69 days PI) significantly enhanced
      the growth of the LCM by 87.6% (1.9-fold). Parasites from praziquantel treatment
      regimens examined ultrastructurally showed consistent damage to the germinal
      membrane evidenced by vacuolization and rupture of syncytial cytoplasm, rupture
      and coalescence of the electron-lucent vesicles just below the microvilli of the
      tegumental surface, and swelling and rounding of mitochondria. At 39 days PI,
      increased blebbing of the germinal membrane into the lumen of the LCM in
      praziquantel-treated animals was observed by scanning electron microscopy. The
      treatment-induced blebs were identified as nucleated germinal cells by
      transmission electron microscopy and appeared to be responsible for metastasis
      and enhanced growth of the LCM. Although praziquantel damaged the ultrastructural
      integrity of the LCM, treatment failed to inhibit larval cyst growth or
      protoscolex development.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304568
TI  - Identification of Trypanosoma brucei gambiense group I by a specific kinetoplast
      DNA probe.
AB  - A set of 26 Trypanosoma brucei stocks from various African countries, previously
      characterized by multilocus enzyme electrophoresis (MLEE) for 18 polymorphic
      loci, have been selected to be representative of the three T. brucei classic
      subspecies. The kinetoplast DNA minicircle variable regions from these stocks
      have been amplified using the polymerase chain reaction (PCR) technique, and
      hybridized with the amplified variable regions of three T. brucei reference
      stocks, previously identified as T. brucei brucei, T. brucei gambiense, and T.
      brucei rhodesiense, respectively. Both T. b. brucei and T. b. rhodesiense probes
      hybridized only with their own stocks, but the T. b. gambiense probe specifically
      hybridized with a group of 12 stocks that represented most of the human stocks
      from West and Central Africa in our sample. These stocks, which appeared as a
      clearly separable cluster based on previous MLEE analysis, probably correspond to
      T. brucei gambiense group I. No other stock hybridized with this amplified
      fragment. Since the T. b. gambiense probe obtained is specific for many isolates
      that are pathogenic for humans in Central and West Africa, it appears to be a
      promising tool for epidemiologic and medical surveys.

PMID- 8304569
TI  - Mortality of Leishmania major in Phlebotomus papatasi caused by plant feeding of
      the sand flies.
AB  - The plant feeding of Phlebotomus papatasi and the effects of plant diets on the
      Leishmania major infections were investigated. Plant-fed flies had small free
      particles and membranous shreds in their gut that were stained by calcofluor as
      cellulosic plant tissues. They were found in 34.0% of the female and 14.3% of the
      male sand flies following feeding on the caper plant (Capparis spinosa). No plant
      residues were found in 54 females that had been fed on plant-derived honeydew
      secretions of Aphis craccivora offered on a branch of the host plant. Calcofluor
      stained particles were also absent from the gut lumen of unfed flies. The
      proportion of sugar feeding, regardless of the intake of plant tissue, in the
      series that had been offered caper plant or honeydew was estimated by testing for
      the presence of fructose in the gut. The proportion of fructose-positive flies in
      each series, among both males and females, was 45%. Plant feeding in the field
      was demonstrated by finding tissue residues in the gut of 32.8% of female and
      10.3% of male P. papatasi from the Jordan Valley. Feeding on specific plants was
      demonstrated using baits of branches suffused with food dye and finding the dye
      marker in wild-caught P. papatasi. The influence of plant diets on L. major
      infections in P. papatasi was as follows: Malva nicaeensis and the honeydew of
      Icerya purchasi produced thriving parasitemias; however, feeding on Ricinus
      communis, Capparis spinosa, and Solanum luteum caused > 50% mortality and
      deformation of parasites in 88%, 55%, and 46% of the infections,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304570
TI  - The China I/CDC strain of Plasmodium malariae in Aotus monkeys and chimpanzees.
AB  - Five Aotus monkeys and two chimpanzees were infected with Plasmodium malariae
      isolated from a patient who acquired her infection approximately 50 years ago.
      All animals were splenectomized. The chimpanzees supported the highest parasite
      densities of 22,271/microliters and 18,544/microliters. Three Aotus monkeys with
      a previous history of infection with P. vivax had maximum parasite counts of from
      1,818/microliters to 2,909/microliters, whereas two monkeys not previously
      infected had maximum parasite counts of 6,908/microliters. The establishment of
      new isolates in these animals aides the development of diagnostic probes and the
      identification of areas of antigenic variation within the species.

PMID- 8304571
TI  - A study of polymorphism in the circumsporozoite protein of human malaria
      parasites.
AB  - We have characterized the circumsporozoite (CS) gene sequences of Plasmodium
      malariae China-1 CDC, isolated recently from a person who was infected 50 years
      ago in China, and P. vivax Chesson, isolated 48 years ago from a patient who had
      returned from New Guinea. These protein sequences were compared with the CS
      protein sequences of recently isolated P. vivax and P. malariae parasites. In a
      similar manner, we compared the previously characterized CS protein gene of P.
      falciparum clone 7G8, derived from a Brazilian isolate collected in 1980, with
      the CS protein genes of recent P. falciparum field isolates. In the case of the
      P. malariae CS protein gene, with the exception of an additional copy of major
      (NAAG) and minor (NDAG) repeat sequences and the presence of one copy of NDEG
      sequence, the China-1 CDC P. malariae parasite is similar to the Uganda-1 CDC
      isolate of 1982. In the nonrepeat region, changes were noted in two amino acid
      residues, one of which is also seen in a closely related monkey malaria parasite,
      P. brasilianum. In the case of P. vivax CS proteins, the nonrepeat region of the
      protein in Chesson strain shares identity with nearly 71% of the CS clones
      characterized from field isolates. In the P. falciparum CS proteins, the 7G8 CS
      protein sequence is identical to 75% of the genes of recent field isolates in the
      Th1R-N1 region. In the Th2R and Th3R regions, 34% and 55% of the CS clones
      analyzed, respectively, had changes at two amino acid residues.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8304572
TI  - Identification of the antigenic constituents of Ehrlichia chaffeensis.
AB  - Ehrlichia chaffeensis, the novel etiologic agent of human ehrlichiosis in the
      United States, was first isolated in 1990 and reported in 1991. To analyze the
      antigenic components of E. chaffeensis, we cultivated these obligate
      intracellular bacteria in DH82 cells, purified the ehrlichiae by renografin
      density gradient centrifugation, and examined the antigens by Western
      immunoblotting. Rabbit and human antisera to E. chaffeensis revealed more than 20
      bands ranging from 20 to 200 kD. The distinct 22-kD protein was heat labile. The
      rest of the major immunoreactive components were heat stable. The immunoblots of
      E. chaffeensis were highly similar when probed with antisera to E. chaffeensis,
      E. canis, and E. ewingii, indicating the close antigenic relationships among the
      three species. The 22-kD protein cross-reacted only with anti-E. canis serum. The
      antibody against E. sennetsu reacted strongly with the 66-, 64-, 55-, and 44-kD
      antigens of E. chaffeensis. The E. risticii antisera reacted strongly with the 55
      and 44-kD bands but only faintly with the 66-kD band. The major immunoreactive
      antigens of E. chaffeensis (66, 55, and 44 kD) showed cross-reactions with all
      the different antisera tested. The results indicated that E. chaffeensis is
      antigenically most closely related to E. canis, is less closely related to E.
      ewingii, and is only distantly related to E. sennetsu and E. risticii.

PMID- 8304573
TI  - The use of a polymerase chain reaction as a diagnostic test for Rocky Mountain
      spotted fever.
AB  - A polymerase chain reaction (PCR) for amplifying ribosomal DNA of Rickettsia
      rickettsii was performed on blood clots and urine samples from 10 patients with
      suspected Rocky Mountain spotted fever (RMSF) and five controls with
      nonrickettsial diseases. The results of this PCR-based procedure were positive in
      four of the five patients with probable RMSF, but reamplification was required in
      three patients. Rickettsia rickettsii was grown from the blood of two of these
      four patients. The urine from one patient was also PCR-positive. These results
      confirm earlier findings that the PCR can detect R. rickettsii, but the need for
      reamplification indicates that the lack of sensitivity is a serious limitation in
      the usefulness of the PCR as a clinical diagnostic test.

PMID- 8304574
TI  - Diagnosis of human hydatidosis: comparison between imagery and six serologic
      techniques.
AB  - Echography and/or chest radiograph in association with six serologic
      (immunologic) methods were tested for their ability to diagnose human
      hydatidosis. The immunologic techniques used were latex agglutination, counter
      immunoelectrophoresis, enzyme-linked immunosorbent assay (ELISA) with whole
      hydatid fluid and with antigen 5, a thermobabile lipoprotein that elicits the arc
      5 precipitin line in immunoelectrophoresis. In this report, the results of
      examinations of 273 patients are presented. Of these, 243 cases were surgically
      proven to have hydatidosis, whereas 30 of the 273 that were strongly suspected of
      having hydatid cysts by radiology were shown to have other pathologies. The ELISA
      was more sensitive than the other methods, with 204 of 243 sera shown to be
      positive. The remaining 39 sera that gave false-negative results were tested
      using two recently developed methods, enzyme-linked immunoelectrodiffusion assay
      (ELIEDA) and immunoblotting (electrophoretic migration of hydatid fluid antigens
      under denaturing but nonreducing conditions, blotting, and immunoenzymatic
      assay). Immunoblotting, using our experimental conditions, had a greater
      sensitivity than the ELIEDA with this technique. Four of 37 sera showed one to
      three bands of 65, 12, and 8 kD. The sensitivity of the ELISA did not increase
      with either the size or type of cyst. Comparison of radiology with serology
      confirmed a good correlation between the two methods. Nevertheless, serology is
      more specific but less sensitive than imagery.

PMID- 8304575
TI  - Immunologic incrimination of Ancylostoma caninum as a human enteric pathogen.
AB  - In northeastern Australia, the incidence of human eosinophilic enteritis (EE) and
      unexplained abdominal pain with peripheral blood eosinophilia (PE) appear to be
      exceptionally high. Because adults of the common dog hookworm, Ancylostoma
      caninum, were found in situ in several cases, we compared specific antibody
      responses in patients with EE or PE with those of individuals from various
      control groups. Sera were obtained from three patients with confirmed dog
      hookworm infection, 25 patients with EE/PE, 42 with other diagnosed
      gastrointestinal disorders, eight with human hookworm infection, 27 with other
      diagnosed parasitic infections, and 100 blood donors from the State of Tasmania,
      where A. caninum does not occur. They were analyzed by enzyme-linked
      immunosorbent assay (ELISA) and Western blot for IgG and IgE antibodies to
      excretory-secretory (ES) antigens from adult A. caninum. In the ELISA, sera from
      88% of EE/PE patients were positive for IgG and IgE antibodies to ES antigen. All
      eight patients infected with human hookworm (identified as A. duodenale in three)
      were also seropositive, while most of those with other parasitic infections, as
      well the blood donors, those with diagnosed gastrointestinal diseases, and the
      control subjects, were seronegative. In Western blots, sera from 92% of EE/PE
      patients demonstrated IgG and IgE antibodies to a component of ES antigen with a
      molecular weight of approximately 68 kD (Ac68), as did all sera from cases
      infected with human hookworms. Among the patients with other gastrointestinal
      disorders and parasitic infections, four of 42 (10%) and three of 27 (11%),
      respectively, reacted positively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304576
TI  - Studies on the prevalence of leishmanin skin test positivity in the Baringo
      District, Rift Valley, Kenya.
AB  - The leishmanin skin test (LST) was applied in 26 clusters of an average of 97
      individuals in Baringo District, Kenya. These clusters were centered around
      recent cases of visceral leishmaniasis (VL). Of 2,411 individuals tested, 254
      (10.5%, 155 males and 99 females) had a positive reaction. Among cured VL
      patients, the frequency was approximately 30% and no sex difference was observed.
      In the population as a whole, LST positivity increased with age to a stable level
      from approximately 15 years of age, reflecting an endemic situation. The level of
      LST positivity was 25-30% and 10-15% in males and females, respectively.
      Uninfected household contacts of VL cases had a higher frequency of LST
      reactivity than the rest of the population. This relationship was significant
      only in females and children, the prevalence ratio being 2.3 (95% confidence
      interval 1.3-4.1), 1.9 (1.1-3.5), and 1.4 (0.8-2.5) for females, children, and
      males, respectively. The frequency of LST positivity was higher individuals
      living in wood houses than in individuals living in house with mud or stone
      walls. Again, this difference was significant only in females and children (P =
      0.02 and P = 0.04), but not in males (P = 0.7). The results suggest that children
      and women are exposed to the parasite in or around their houses, whereas adult
      males are, in addition, exposed elsewhere.

PMID- 8304577
TI  - Community participation in malaria surveillance and treatment. III. An evaluation
      of modifications in the Volunteer Collaborator Network of Guatemala.
AB  - In most rural areas of Latin America, malaria surveillance and treatment is
      carried out by a network of unpaid village malaria workers, known as Volunteer
      Collaborators, who are trained and supervised by the National Malaria Service. To
      identify ways in which the performance of these volunteer workers could be
      improved and to test changes that would make the Volunteer Collaborator Networks
      (VCNs) a more attractive model for community participation in malaria case
      detection and treatment in other regions, we tested a series of modifications in
      the VCN of Guatemala. These modifications included improved methods for
      selecting, supervising, and evaluating the volunteer workers and for collecting
      blood smears and reporting results, and the use of volunteer workers, known as
      Volunteer Medicators, who administered presumptive antimalarial therapy without
      taking a blood smear. A cost-effectiveness analysis of the modified VCN was also
      carried out. Two years after the modifications were introduced, Volunteer
      Collaborators identified nearly twice as high a percentage (33% versus 17%) of
      patients with suspected malaria in their villages. Delays in examining blood
      smears were reduced from 23 days to 11 days and delays from blood smear
      examination to curative treatment were reduced from 21 days to 7 days. The
      Volunteer Medicators identified and treated only a slightly higher percentage of
      patients than the Volunteer Collaborators (36% versus 33%). However, the cost of
      maintaining a network of Volunteer Medicators ($0.61 per patient treated) was
      much lower than the traditional VCN ($2.45) or the modified VCN ($1.85). Thus,
      with a few, simple and relatively inexpensive modifications, the efficiency and
      cost-effectiveness of Volunteer Collaborators can be markedly improved.
      Additionally, the VCN can be modified to make it a more suitable model for
      community-based malaria control and surveillance networks in other malarious
      areas of the world, which differ in terms of their level of endemicity, the goals
      of the malaria program, or the available health care infrastructure.

PMID- 8304579
TI  - [Disconnections in the breathing system].
AB  - Modern anaesthesia is considered as relatively safe. Nevertheless, incidents
      happen which result in harm for the patient. Incidents which cause hypoxia are
      especially grave. One of the most frequent incidents in anaesthesia and intensive
      care is of this nature: disconnection in the ventilatory apparatus. DEFINITION.
      Unintentional separation--partial or complete--of two manually connected
      components in a ventilatory apparatus. INCIDENCE. About 5% of incidents during
      narcosis are likely to be caused by disconnections in the ventilatory apparatus.
      CAUSES. Axially directed force of as little as 15 N may cause disconnection. It
      may result from active or passive movements of the patient, high pressure in the
      apparatus or unintentional traction on the breathing hoses. Conically moulded
      couplings are mostly used for connections. The stability of these so-called taper
      fit connections is decisively determined by the effort and technique of the user
      when coupling the two components. On the other hand the use of unsuitable
      materials may lead to an inadequate connection. Another possibility is damage by
      mechanical, chemical or thermal influences. Additionally, differences from the
      standard specifications of the components may occur. MOST COMMON SITES.
      Disconnections are found predominantly (in around 70% of cases) at the connection
      between the tube connector and the adapter or Y-piece. This joint represents a
      weak point, especially during surgical treatment in the head and neck region,
      when it cannot be controlled and in most cases is not accessible by hand because
      it is covered. CONSEQUENCES. The consequences of disconnection depend on
      different factors: relaxation of the patient, depth of narcosis, duration and
      localization of the disconnection, constitution and current oxygenation of the
      patient. An undetected disconnection may lead to hypoxia within a few minutes and
      then to irreversible brain damage and finally death. Serious incidents have been
      decreased in number in recent years by the application of improved monitoring
      procedures. DETECTION. Measurements of airway pressure, minute volume and
      expiratory CO2 by capnography ensure rapid detection of disconnections using
      appropriate adjustments of alarm limits. A disconnection may not be detected by
      pulse oximetry before a latent period, i.e. after a significant decrease of the
      oxygenation saturation of the patient. PREVENTION. Standardized specifications
      exist for technical dimensions of connectors, but "reliability" of connectors has
      not yet been defined in terms of technical requirements. Disconnection is
      currently prevented by application of various mechanical methods and devices, not
      all of which fulfil the conditions required of an ideal system: (1) Simple and
      fast connection ("single-handed operation"); (2) connection independent of the
      torsional angle between the two parts; (3)safe connection which cannot be
      detached unintentionally; (4) 360 degrees torsion possible after connection; (5)
      tight connection; (6) fast and easy deliberate disconnection; (7) intentional
      disconnection possible independent of the torsional angle between the two parts;
      (8) compatibility with conventional systems; (9) user's comfort and convenience
      (when ventilating with mask, etc.) as good as with conventional systems.
      DISCONNECTION OR EXTUBATION? There is a heated debate on the theme
      "disconnection". Some authors suspect that the development of reliable locking
      connections could lead to an increased frequency of unwanted extubations. To
      prevent unwanted extubations with consequent harm to patients, some developers
      propose a mechanical fuse, i.e. a defined site of fracture with an additional
      adequate monitoring device for reliable detection of disconnections. CONCLUSIONS.
      There are many approaches to the "disconnection" problem. In principle the
      problem requires a fundamental decision for each connection in the breathing
      system: safe prevention of disconnection (lock connection) or reliable mechanical
      f

PMID- 8304578
TI  - Sherlock Holmes and tropical medicine: a centennial appraisal.
AB  - Sir Arthur Conan Doyle incorporated an unidentified tropical disease as a murder
      weapon in the Sherlock Holmes story, "The Dying Detective," written in 1913.
      Documentary and circumstantial evidence suggests that the disease mentioned was
      melioidosis. The description of the newly identified disease occurred shortly
      before Doyle's death. Doyle's other works at the time reflect a consistent
      interest in tropical disease.

PMID- 8304580
TI  - [Quality control of platelet concentrates. Functional assessment of stored
      platelets in vitro].
AB  - Platelet concentrates transfused for correction of thrombocytopenia or reduced
      platelet function do not consistently improve primary haemostasis in the
      recipient. Insufficient therapeutic effects may be caused by impaired donor
      platelet function and by unfavourable donation and storage conditions, as well as
      by immunological interactions with the recipient blood. The present study was
      designed to investigate whether the effect of platelet transfusion on recipient
      platelet function can be predicted by in vitro methods. METHODS. Blood samples
      were taken from 12 thrombocytopenic patients before (20 ml, P0) and after (10 ml,
      P(vivo)) transfusion of one unit of platelets previously stored for 24-120 h in
      acid citrate dextrose. An additional sample was taken from the platelet
      concentrate (TK) immediately before transfusion. P0 was divided into two
      specimens and TK platelets were added to one of them (P(vitro) in order to obtain
      a platelet count similar to that in P(vivo). Bleeding time (BT) and bleeding
      volume (BV) of the samples P0, P(vivo) and P(vitro) were measured using the
      method of Kratzer and Born (Fig. 2); mean values were calculated for each sample
      from six measurements. Aggregability of TK platelets was determined in addition
      by aggregometry. In contrast to previous studies, physiological Ca2+
      concentrations were restored and secondary haemostasis was inhibited by low
      molecular-weight heparin (Fragmin P, Pfrimmer Kabi GmbH und Co. KG, Erlangen) in
      the platelet-rich plasma used for aggregometry. RESULTS. Platelet counts
      increased in all patients after transfusion (P(vivo) vs P0, Table 1) and were
      nearly identical in P(vitro) and P(vivo) (r = 0.94, P < 0.001; Fig. 3).
      Parameters of primary haemostasis were significantly improved by addition of
      platelets to P0 in vitro (BT P < 0.05, BV P < 0.01) as well as by platelet
      transfusion (BT P < 0.05, BV P < 0.01). Direct comparison of P(vitro) and P(vivo)
      yielded a very close correlation of BT (r = 0.88, P < 0.001) and BV (r = 0.89, P
      < 0.01) in both samples. Although aggregometry revealed decreasing platelet
      function with increased storage time, aggregability was considerably higher
      compared to previous studies of platelet concentrates stored for 2-5 days.
      CONCLUSION. A new technique has been developed which allows reliable prediction
      of the effect of platelet concentrates on primary haemostasis of the recipient by
      in vitro measurement of bleeding time and bleeding volume prior to transfusion
      using the method of Kratzer and Born.

PMID- 8304581
TI  - [Perioperative enzyme therapy. A significant supplement to postoperative pain
      therapy?].
AB  - METHODS: Following ethics committee approval and with written informed consent,
      80 patients (61 female, 19 male) were randomly allocated in this double-blind,
      placebo-controlled, parallel group study to two groups of 40 patients each. The
      treatment group received a compound of proteolytic, glycolytic, and lipolytic
      enzymes and rutoside (Wobenzym), while the control-group received placebo.
      Efficacy and tolerance of the study medication was examined before and after day
      case surgery for the carpal tunnel syndrome. Medication was given 10 tabs t.i.d.
      for 15 days, starting 7 days before surgery. Pain intensity (visual analogue
      scale), intake of analgesics, and tolerance of the study medication were recorded
      daily and treatment differences between the two groups were statistically
      evaluated. RESULTS: Comparison of demographic data of all enrolled patients
      showed no significant difference between the two groups. In the enzyme group,
      pain scores were lower on the day of operation and for the following 5 days but
      did not differ significantly from the control group; however, patients of the
      enzyme group took significantly less analgesics and experienced significantly
      earlier pain relief than those of the control group, thus demonstrating a pain
      reducing effect of the enzyme compound. Only few side effects were reported in
      both groups, none of them serious. CONCLUSION: Enzyme therapy is an effective and
      safe adjuvant treatment for the control of postoperative pain.

PMID- 8304582
TI  - [Much ado about the lesser circulation].

PMID- 8304583
TI  - [Anesthesia equipment and respirators. Fundamentals].
AB  - The decrease of functional residual capacity during anaesthesia makes mechanical
      ventilation mandatory. Volume- and pressure-controlled modes should both be
      possible. Ventilator-assisted spontaneous respiration is rarely indicated during
      general anaesthesia, and this mode is therefore unnecessary for anaesthesia
      machines. From ecological and economical points of view, modern anaesthesia
      machines should be equipped with a circle system enabling administration of
      anaesthesia under rebreathing conditions with reduced fresh gas flow. Basic
      requirements are low gas leakage of the system, precise gas-flow dosage,
      especially at low flow rates, and integrated monitoring of in- and expiratory
      gases. In principle, older machines may also comply with these requirements if
      they are appropriately upgraded and properly maintained. There is reasonable
      doubt whether a further reduction of flow to less than 1 l/min fresh gas is of
      any benefit. To maintain patient safety without compromising practicability, a
      tremendous surplus of technical efforts is necessary. For easier management,
      fresh-gas-flow-compensated circle systems facilitating adjustment of tidal volume
      after changes of fresh gas flow are desirable. Precautions aimed at the
      prevention of ventilation with hypoxic gas mixtures are still insufficient: the
      oxygen failure devices (nitrous oxide flow shutoff valve) are only effective if
      oxygen pressure from the gas supply is low. Distinct improvements have been
      achieved with oxygen ratio systems, preventing the administration of hypoxic gas
      mixtures at fresh gas flows higher than 1 l/min.

PMID- 8304584
TI  - Functional morphology of the nictitating membrane in the domestic cat.
AB  - Morphological differences between the corneal and palpebral surfaces of the
      nictitating membrane of the domestic cat were examined using histology,
      histochemistry and the scanning electron microscope. Both surfaces are covered by
      one or two layers of epithelial cells. The epithelium contains numerous goblet
      cells, particularly on the palpebral side. These cells revealed binding sites for
      six lectins as well as positive PAS reactivity, and alcianophilia at both pH 2.5
      and pH 3.5. Numerous lymph follicles located on the corneal side make the
      epithelium look like lymphoepithelial tissue. Accumulations of lymphatic tissue
      may also be found on the palpebral side. Scanning electron micrographs showed
      microvilli on the epithelial surfaces. The function of the cat nictitating
      membrane is discussed on the basis of our findings and those of other authors.
      Movements of the nictitating membrane alternate between active and passive phases
      of gliding. The membrane as a whole effectively protects the nasal portion of the
      bulb from dust, dehydration and pathogens.

PMID- 8304585
TI  - Reinvestigation of the transitional epithelium (urothelium) of the human ureter.
AB  - The transitional epithelia (urothelia) of the ureters of 30 patients of different
      ages were studied by means of light and electron microscopical, histochemical and
      immunocytochemical methods. A great variability of the normal structural
      appearance of the urothelium was established. Structural features and the uptake
      of exogenous peroxidase by the surface epithelial cells provided high endocytotic
      activity. Urothelial cells take up many low and high molecular weight substances
      from the urine and further metabolize and transport these toward the
      subepithelial connective tissue. Lymphocytes, macrophages, monocytes, plasma
      cells and rarely polymorphonuclear leukocytes are distributed intra- and
      extraepithelially and are involved in the immunological response to agents which
      enter the intercellular spaces of the epithelium. These cells are also
      responsible for the elimination of aged and degenerating superficial squamous
      cells. The present investigation establishes the existence of immunological
      defence mechanisms in the adult human urothelium. The results obtained suggest
      that the human ureter contains three functional barriers directed against
      aggressive components of the urine: the first represented by structures of the
      superficial squamous cells, the second by the upper cells of the ureteric
      intermediate layer and the third comprising epithelial and immunological cells
      involved in immune defence mechanisms.

PMID- 8304586
TI  - [GFAP immunoreactivity in newly formed ileal mucosa in a serosal patch in dog
      colon].
AB  - A Short bowel was induced in 8 beagle bitches by resecting 85% of the small
      intestine. Following resection, a tangential fixation was performed in
      antiperistaltic direction between the ileum and the proximal colon. A 15 cm
      segment of the remaining ileum was incised opposite to its mesenterial attachment
      and sewn onto the serosa of the neighboring segment of colon (Serosa patching).
      After 20 weeks of observation, segments of the ileum, the colon and the
      anastomosed intestinal segment were removed. The neomucosa covering the patch
      surface was investigated using immunohistochemical methods in order to
      demonstrate the presence of nerve fibers. The immunofluorescence reaction using
      anti-GFAP (glial fibrillary acidic protein) clearly demonstrated immunoreactivity
      in the formed neomucosa and in the underlying granulation tissue. The
      immunoreactive fibers were comparable with fibers demonstrated in the original
      mucosa. This finding is an indication that the neomucosa of a serosa patch may be
      functionally intact because the presence of nerves suggests that mucosal
      functions, e.g. resorption and secretion, are under nervous regulation.

PMID- 8304587
TI  - Localization of uteroglobin mRNA by nonradioactive in situ hybridization in the
      pregnant rabbit endometrium.
AB  - The distribution of uteroglobin mRNA has been investigated in the endometrial
      compartments of the rabbit uterus during early pregnancy (day 0.5 p.c.--day 12
      p.c.) using nonradioactive in situ hybridization. Digoxigenin-dUTP labeled
      oligodesoxy-nucleotide-probes (24mer) and an anti-digoxigenin-antibody conjugated
      with alkaline phosphatase were developed and used. It could be shown, that
      uteroglobin mRNA localization is restricted to the endometrial epithelium. There
      are differences in the extent of uteroglobin mRNA expression within the
      epithelial cells, which is in accord with our interpretation on the existence of
      different epithelial cell populations. From day 0.5 p.c. to day 9 p.c. the cells
      of the basal glands express uteroglobin mRNA continuously, whereas the
      proliferating surface epithelium shows a remarkable fluctuating pattern of
      uteroglobin mRNA expression. On day 2 p.c. the whole surface epithelium starts to
      express the uteroglobin message, and up to day 5 p.c. all these cells show a high
      level of uteroglobin mRNA expression, which drops significantly on day 6 p.c.,
      when significant changes in the cyto-morphology of the surface epithelium for
      implantation occur. On day 7 p.c., there is no more uteroglobin mRNA expression
      in the surface epithelium, however remaining expression in the basal glands. The
      latter is evident up to day 9 p.c. From day 10 p.c. onwards, neither the luminal
      nor the deep glandular epithelium express any uteroglobin mRNA. Our observations
      on the cellular level have been continued in parallel studies on endometrial
      homogenates by Northern Blot analysis of uteroglobin mRNA (600 bases). Finally,
      it is discussed whether Uteroglobin mRNA may be an useful marker for the
      differentiation of various endometrial epithelial cell populations.

PMID- 8304588
TI  - Experimentally induced lipidosis in uterine and vaginal epithelium of rats.
AB  - The purpose of this study was to investigate the effects of two lipidosis
      inducing drugs (the anorectic drug chlorphentermine and the tricyclic
      antidepressant-imipramine) upon the estrous cycle of rats and upon the morphology
      of the vaginal and uterine epithelia. After two weeks of continuous
      administration of high daily drug doses, the estrous cycle became stagnant.
      Ultrastructurally, the vaginal and uterine epithelia contained storage lysosomes
      which were filled with undigested polar lipids appearing as multilamellated
      material. The uterine luminal epithelium was most severely affected. The estrous
      cycle was abolished also by treatment with the anorexigenic drug phentermine,
      although this compound does not cause lipidosis. Therefore, the cessation of the
      estrous cycle cannot be attributed to the lipidosis as induced by
      chlorphentermine and imipramine; probably it is a consequence of the main actions
      of these psychotropic drugs. The biological basis for the exceedingly severe
      lipidosis in the uterine luminal epithelium is suggested to be the heavy load of
      polar lipids physiologically delivered to the lysosomal apparatus as long as the
      cycle-dependent apoptotic and autophagic processes were going on during the early
      period of drug treatment.

PMID- 8304589
TI  - HOE-BAY 946 has distinct effects on spontaneous and FGF induced proliferation of
      epithelial and neuroblastoma cell lines.
AB  - We have studied in vitro the effects of HOE-BAY 946, a specific inhibitor of
      tyrosine kinase C, on spontaneous and basic FGF-induced proliferation of the
      epithelial cell lines A549 and HELA as well as the neuroblastoma cell line SY5Y
      using a fully automated colorimetric assay for determinations of cell numbers.
      HOE-BAY suppressed spontaneous proliferation of the epithelial lines, but not the
      neuroblastoma line, both in the presence and absence of serum. In contrast, the
      drug completely abolished the mitogenic effect of basic FGF on all cell lines.
      This suggests an involvement of a tyrosine kinase C activity in the transduction
      of the FGF signal both in the epithelial and neuroblastoma lines. Since the
      action of FGF on non-transformed neuronal cells is accompanied by a down
      regulation of kinase C, and kinase C activation blocks the FGF effects, our data
      indicate that differentiative and mitogenic effects of FGF on neuronal cells may
      employ different transduction mechanisms.

PMID- 8304590
TI  - Aging of nucleolar organizer region in rat basal forebrain neurons related to
      learning and memory.
AB  - The nucleolar organizer of rat basal forebrain neurons was studied with
      histochemical and morphometrical techniques, in order to analyze quantitatively
      the morphological correlate of activity as it changes during learning and aging
      of the brain. The learning abilities of adult (2 months) and senile (30 months)
      rats were tested with a conditioned response learning paradigm. Four groups of
      rats were defined: one group consisted of untrained adults, a second group
      consisted of trained adults, and the senile rats were subdivided into one group,
      which was able to learn and another group which was not able to perform the test.
      Frozen sections through the basal nucleus were silver stained to visualize the
      nucleolar organizer and the area of its profile was measured. The data showed
      that the nucleolar organizer in both the trained adult and the senile rats who
      were able to learn, was much larger than that in the untrained adults and the
      senile rats who were not able to learn. In the latter groups the nucleolar
      organizers were of equal size. An additional finding was, that the senile rats
      who could not be trained, showed a lower neuronal density in the basal nucleus
      compared with that of the trainable senile and adult rats. The changes in the
      size of the nucleolar organizer are interpreted as a morphological sign of
      learning-induced increases in transcription and synthesis of ribosomal RNA.

PMID- 8304591
TI  - Blood monocytes and spleen macrophages differentiate into microglia-like cells
      when cultured on astrocytes.
AB  - Microglial cells are resident immunoeffector cells of the central nervous system.
      They differ from most other resident macrophages by their ramified shape, their
      capacity to proliferate, and by a distinct pattern of ion channels. They have
      therefore been proposed to be a subpopulation of macrophages that arise from a
      distinct pool of myelomonocytes by early determination of their lineage within
      the bone marrow. Here we present data which show that distinct properties of the
      microglial cells are not intrinsic to this subpopulation of macrophages, but are
      acquired subsequent to their interaction with astroglial cells, since similar
      properties can be induced in both blood monocytes and spleen macrophages, when
      these are cultured on astrocytes. These findings add further evidence to the
      proposition that microglial cells are derived from the myelomonocytic lineage,
      and also indicate that the properties of resident macrophages are largely
      determined by tissue components of the host organ.

PMID- 8304592
TI  - Endometrial receptivity: cell biological aspects of an unusual epithelium. A
      review.

PMID- 8304593
TI  - The influence of altered occlusion on the condylar cartilage of the mandible and
      on the growth of the entire skull.
AB  - The effect of the loss of the suspensory zones of the upper jaw on the cartilage
      of the mandibular condyles and on the growth of both the viscerocranium and the
      neurocranium was examined after tooth crowns had been reduced in Wistar rats. We
      measured the thickness of the individual layers of the condylar cartilage and its
      total thickness. Alterations in the developmental processes involving the
      condylar cartilage expressed themselves as accelerated maturation, particularly
      in the centrally compressed areas of the cartilage. Alterations in occlusion
      influenced the development of the viscerocranium, whereas no influence on the
      growth of the neurocranium was detected.

PMID- 8304594
TI  - Post-embedding immunocytochemistry for adhesive proteins and clathrin in LR White
      and LR Gold-embedded human platelets.
AB  - Two hydrophilic acrylic resins, LR White and LR Gold, were tested for their
      suitability for post-embedding immunocytochemistry on human platelets. Both
      resins gave satisfying results with regard to ultrastructural preservation and
      retention of antigenicity for von Willebrand factor, fibrinogen, fibronectin and
      clathrin. Embedding in LR White and polymerization at 50 degrees C without
      accelerator proved to be the best method because it provided clear negative
      membrane contrast, good immunocytochemical localization of antigens and the
      entire procedure required a comparatively short time. Label for von Willebrand
      factor was found in typically eccentric location in alpha-granules, but also in
      the form of small caps directly outside the granule membranes, beneath the outer
      plasma membrane and in the cytoplasm. With the exception of the eccentric
      location within granules, labelling for fibrinogen and fibronectin revealed very
      similar results. Label for clathrin appeared in the form of small gold clusters
      attached to alpha-granules, in the cytoplasm and beneath membranes of the open
      canalicular system. Together with the appearance of coated vesicles attached to
      granules and to the membranes of the open canalicular system in araldite-embedded
      material, these results further strengthen the concept that adhesive proteins are
      taken up from the plasma and stored in granules. Moreover, the persistence of the
      clathrin coat on vesicles attached to storage granules may also indicate that
      receptors for adhesive proteins are recycled.

PMID- 8304595
TI  - The structure and vascularization of the biceps brachii long head tendon.
AB  - In the present study we examined the structure and the blood supply of the long
      biceps tendon as well as the surface of the intertubercular sulcus, using tissue
      samples from children and adults. The applied methods were light and electron
      microscopy, immunohistochemistry, and arterial injection techniques. The tendon
      represents a sliding tendon with the intertubercular sulcus and humeral head as
      hypomochlion. The parts facing the humerus show some ultrastructural features of
      fibrous cartilage, the ovoid chondrocyte-like cells of the tendon lying within
      felt-like matrix. In the opposite part adjacent to the capsule, the tendon
      resembles a traction tendon. The intertubercular sulcus is covered by fibrous
      cartilage. The tendon is supplied with arteries from three different sources. The
      density of intratendinous vessels in the traction zone is comparable to that of
      other tendons, while in the sliding zone it is markably decreased. The immediate
      vicinity of the sliding surface is avascular. Our findings show that the long
      biceps tendon is structurally adapted to both its functions as sliding and
      traction tendon. The blood supply seems to be related to the metabolic
      requirements of the different parts of the tendon.

PMID- 8304596
TI  - An anatomical study of the healthy human heart by echocardiography with special
      reference to physiological valvular regurgitation.
AB  - 110 healthy subjects (45 men and 65 women ranging in age between 24 and 60 years)
      were studied by 2-dimensional echocardiography. In each subject the diameters of
      the cardiac chambers, the thickness of the intraventricular septum and posterior
      wall of the left ventricle in diastole, as well as the diameters and
      circumferences of the aortic and mitral rings were measured. Moreover, in each
      subject color doppler echocardiography was performed. Pulmonary valve
      regurgitation was observed in 47 subjects (42.7%). This finding was not
      correlated in a statistically significant manner to either age, sex, body weight,
      or height. The incidence of pulmonary regurgitation, however, tended to decrease
      with age. In 37 subjects (33.6%), tricuspid regurgitation was detected without
      any correlation to the above parameters. In 11 cases (10%), mitral regurgitation
      was observed; its correlation to age was statistically significant (p < 0.05).
      Aortic regurgitation was noted in 9 (8.2%) cases; its incidence was directly
      correlated to age (p < 0.01). The observed regurgitations were defined as
      "physiological" and precise characteristics were chosen so as to distinguish such
      "physiological" from "pathological" regurgitations.

PMID- 8304597
TI  - Tubular networks in soleus muscle fibers of the rat following tenotomy. I.
      Spatial organization.
AB  - Complex systems of tubules, 30-40 nm in diameter, were observed in myofibers of
      the soleus muscle of Wistar rats following experimental transection of the
      Achilles tendon. The appearance of these systems varied remarkably, depending
      upon the plane of sectioning. The spacial arrangement of the tubules was
      reconstructed by comparing several sections through individual systems. Such
      reconstructions revealed that they are networks of tubular elements arranged in
      an hexagonal pattern. A three-dimensional wire model was prepared, illustrating
      the spatial organization of the tubular systems. The model consists of four
      groups of lattices with a honeycomb-like arrangement. The lattices of each group
      are parallel to one another, and intersect those of the other groups at an
      inclination of 60 degrees.

PMID- 8304598
TI  - pH-induced denaturation of spectrin changes the interaction of membrane proteins
      in erythrocyte ghosts. Biochemical and electron microscopic evidence.
AB  - The influence of different buffer pH values on the properties of spectrin in
      erythrocyte ghosts and on isolated spectrin was investigated. Ultrastructural
      findings and the results of biochemical studies show that denaturation and
      aggregation of spectrin molecules rather than disulfide crosslinking are
      responsible for the precipitation of spectrin in acidic buffer. Since hemolysis
      in hypotonic buffer at pH 6.0 yields ghosts with spicules and microvesicles, the
      structure of spectrin in intact cells might also be changed and lead to the
      clustering of transmembrane proteins and the aggregation of components of the
      cytoplasmic network.

PMID- 8304599
TI  - Emergency department analgesic use in pediatric trauma victims with fractures.
AB  - STUDY OBJECTIVE: To investigate the frequency of emergency department analgesic
      use in children with presumably painful fractures who are also at risk for
      associated multiple injuries and to determine whether there are specific factors
      that distinguish those who are prescribed analgesics from those who are not.
      DESIGN: Descriptive, retrospective review of a computerized trauma registry.
      SETTING: Regional pediatric ED and trauma center. PARTICIPANTS: Four hundred
      thirty-three injured children met trauma team activation criteria from January 1,
      1991 through June 30, 1992. Of these 433, we selected the 121 children who had
      fractures of the pelvis, long bones, ankle, wrist, or clavicle. Of these 121, we
      excluded the 22 children who underwent endotracheal intubation. Trauma registry
      data from the prehospital and ED phases of care from the remaining 99 children
      were reviewed for this study. INTERVENTIONS: None. MAIN RESULTS: Of the study
      group, 53% (52 of 99) received analgesics, all narcotics. Excluding the 46
      children with multi-system injuries, only 62% (33 of 53) received analgesics.
      Patients in both the analgesic (52) and no-analgesic groups (47) were mildly to
      moderately injured based on initial ED trauma scores and vital signs. No
      statistical or clinical significant differences were found between the analgesic
      group and the no-analgesic group when comparing age, sex, race, mechanism of
      injury, vehicle speed, height of fall, time elapsed from injury until arrival at
      the ED, transport method, prehospital analgesic use, mortality, Injury Severity
      Score, and initial ED vital signs, Glasgow Coma Scale, Trauma Score, and
      Pediatric Trauma Score. Fifty-nine percent (ten of 17) of the children with
      associated internal injuries limited to the chest or abdomen received analgesics
      compared with 62% (33 of 53) in those with isolated fracture (P = .8). Those with
      an associated head injury (31%, nine of 29) received analgesics less frequently
      than those with isolated fracture (62%, 33 of 53) (P = .01). CONCLUSION: Our
      results suggest that ED analgesic use was low in these mildly to moderately
      injured children with presumably painful fractures who are also at risk for
      associated multiple injuries. Head injury was associated with especially low
      analgesic use. We did not identify other specific factors that distinguished
      those who received analgesics from those who did not. Further investigation is
      required to determine if after the initial evaluation, a larger proportion of
      mildly to moderately injured trauma victims with fractures are appropriate
      candidates for ED analgesic use.

PMID- 8304600
TI  - Neutral cervical spine positioning in children.
AB  - STUDY OBJECTIVES: To determine the height of back elevation required to place the
      cervical spine of children less than 8 years old in neutral position and whether
      agreement on the height required for neutral position could be reached by two
      independent observers. STUDY DESIGN: Prospective. SETTING: Pediatric emergency
      department and outpatient clinics. TYPE OF PARTICIPANTS: Convenience sample of
      children less than 8 years old. INTERVENTIONS: Independent placement of children
      in neutral position by two observers using standard sized padding with or without
      shims to raise the back off a backboard. MEASUREMENTS AND RESULTS: All children
      required elevation of the back for correct neutral position (mean height, 25.4 +/
      6.7 mm; range, 5 to 41 mm). Children less than 4 years old required more
      elevation than those > or = 4 years old (27 +/- 7.2 vs 22 +/- 4.2 mm, P < .05).
      Independent observer measurements were similar (mean, 25 +/- 8.0 vs 25.7 +/- 6.8
      mm; interobserver kappa = .56). CONCLUSION: Children less than 8 years old
      require back elevation to achieve neutral position while lying supine on a
      backboard. Also, independent observers can agree on what constitutes neutral
      position in most children.

PMID- 8304601
TI  - The routine use of radiography and arterial blood gases in the evaluation of
      blunt trauma in children.
AB  - STUDY OBJECTIVE: To evaluate the usefulness of routine radiographs and arterial
      blood gases in children with blunt trauma. DESIGN: Retrospective chart review.
      TYPE OF PARTICIPANTS: Ninety patients who met triage criteria for our trauma team
      evaluation and who were less than 15 years old were evaluated. Patients with a
      Glasgow Coma Scale score (GCS) of 15 (lie, mild to moderately injured children)
      were the focus of this study. METHODS: Children seen from May 1991 through August
      1992 had charts reviewed systematically and within 24 hours of emergency
      department evaluation. Standard radiologic evaluation, including cervical-spine,
      chest, and pelvic radiographs, as well as arterial blood gas analysis, were
      obtained. The severity of injury was graded according to the Modified Injury
      Severity Scale. RESULTS: The mean age of patients was 6.4 years, and the injuries
      observed were exclusively extremity fractures. The correlation between physical
      examination findings and radiologic evaluation was assessed. Forty-three patients
      had an abnormal physical examination (ie, gross deformity, limitation of motion,
      or pain), and 26 had a fracture identified on radiograph. Forty-seven patients
      had a normal physical examination and none had a fracture identified on
      radiograph (P < .001; sensitivity of positive signs and symptoms, 100%; false
      negative findings, 0%). Four patients with abnormal blood gases are described. No
      patient had any vascular or solid organ injury identified. CONCLUSION: In
      children with a GCS score of 15, selected radiologic and laboratory tests based
      on clinical findings are recommended. Careful observation and repeat examinations
      by trained clinicians can select a group of children at low risk for occult
      injury.

PMID- 8304602
TI  - Rectal diazepam for prehospital pediatric status epilepticus.
AB  - STUDY OBJECTIVES: To compare the feasibility, effectiveness, and safety of rectal
      diazepam and intravenous diazepam in the treatment of pediatric prehospital
      status epilepticus. DESIGN AND SETTING: Retrospective analysis of a 30-month
      consecutive sample of ambulance-transported children in a large urban emergency
      medical service region. TYPE OF PARTICIPANTS: Study group included 324 patients
      with seizure who were less than 18 years of age; 36 had status epilepticus, of
      whom 16 received rectal diazepam and 15 received IV diazepam. INTERVENTIONS: For
      children with status epilepticus, paramedics administered the 5-mg/mL IV solution
      of diazepam by one of two routes: rectally either through a 5F feeding tube with
      an attached syringe or by lubricated tuberculin syringe inserted 4 to 5 cm into
      the rectum at a one-time dose of 0.2 to 0.5 mg/kg or intravenously using a one
      time dose of 0.1 to 0.3 mg/kg. Cardiopulmonary status was carefully monitored in
      the field and emergency department. MEASUREMENTS AND MAIN RESULTS: Thirteen of 16
      children (81%) who received rectal diazepam stopped seizing after a single dose
      ranging from 0.16 to 0.57 mg/kg. Convulsions recurred before arrival at the ED in
      four of the 13 (30.8%). All of three patients who did not respond to rectal
      diazepam initially were 3 to 5 years old and had serious underlying comorbidity;
      two required endotracheal intubation in the ED and multiple anticonvulsants to
      terminate the seizure. No child treated with rectal diazepam required prehospital
      endotracheal intubation. All children who received IV diazepam stopped seizing
      after one dose ranging from 0.04 to 0.33 mg/kg. Convulsions recurred before
      arrival at the ED in nine of 15 children (60%); two required prehospital
      endotracheal intubation for profound respiratory depression. CONCLUSION: Rectal
      diazepam is a simple, effective, and safe method of prehospital management of
      pediatric status epilepticus. Compared with IV diazepam, rectal diazepam is
      easier to administer, especially in infants and toddlers; is equally efficacious;
      and is less likely to produce respiratory depression. Although respiratory
      depression is rare with rectal diazepam, prehospital personnel must be prepared
      to provide definitive respiratory support. Short duration of action is an
      important limitation of both treatments.

PMID- 8304603
TI  - Suprapubic bladder aspiration versus urethral catheterization in ill infants:
      success, efficiency and complication rates.
AB  - STUDY OBJECTIVE: To compare success rates, complications, and efficiency of
      suprapubic bladder aspiration with urethral catheterization in ill infants.
      DESIGN: Prospective, randomized clinical study. SETTING: The pediatric emergency
      department at the University of Mississippi Medical Center in Jackson.
      PARTICIPANTS: Convenience sample of infants under 6 months of age requiring an
      uncontaminated urine specimen for the evaluation of febrile illness, suspected
      urinary tract infection, or sepsis. Infants with wet diapers were excluded.
      INTERVENTIONS: Patients were randomized to undergo timed suprapubic bladder
      aspiration (performed by a physician and a nurse) or urethral catheterization
      (performed by two nurses). If suprapubic bladder aspiration was unsuccessful,
      urethral catheterization was performed immediately and the bladder was drained;
      emptying volume was recorded. All patients had a next-void "bag" urinalysis
      performed for post-procedure hematuria. RESULTS: Fifty patients underwent primary
      suprapubic bladder aspiration. The success rate (defined by obtaining at least 2
      mL of urine) was 46%. Mean +/- SD time per successful suprapubic bladder
      aspiration was 16.73 +/- 7.73 seconds. Fifty patients underwent primary urethral
      catheterization. The success rate was 100%; the mean time required was 80.70 +/-
      46.52 seconds. After failed suprapubic bladder aspiration, urethral
      catheterization was 100% successful, with a mean draining volume of 2.95 +/- 2.38
      mL. No immediate problems were identified among any instrumented patients; later
      complications (next-void hematuria after either procedure, other visceral injury
      with suprapubic bladder aspiration) were not detected. CONCLUSION: Both
      suprapubic bladder aspiration and urethral catheterization afford the emergency
      physician low-risk access to uncontaminated urine in ill infants. Suprapubic
      bladder aspiration is less efficient in that it requires physician participation
      and failure rates are higher. These data suggest that successful suprapubic
      bladder aspiration is primarily dependent on the volume of urine in the bladder;
      thus, in the ill or febrile ED infant who may be dehydrated, the likelihood of
      success decreases. The authors recommend that ED nursing and physician staff
      become comfortable with performing urethral catheterization on infants.

PMID- 8304604
TI  - Fatal childhood injury patterns in an urban setting.
AB  - STUDY OBJECTIVE: To describe fatal childhood injury patterns in an urban county
      and evaluate the use of the emergency medical services system. DESIGN:
      Retrospective chart review of medical examiner files, prehospital and hospital
      records, and police and fire personnel reports. SETTING: Milwaukee County,
      Wisconsin, an urban county with a population of approximately 1 million.
      PARTICIPANTS: All children 15 years old or younger who sustained a fatal injury
      in 1989 or 1990 (70). RESULTS: House fires were the leading cause of death by
      injury (34%), followed by firearms (19%), and drowning (11%). Motor vehicle
      occupant deaths occurred less frequently (7%). One-third of deaths were homicides
      (48% firearms and 30% assault). Twenty-four percent of deaths were pronounced at
      the scene, 12% were dead-on-arrival (no emergency department resuscitative
      efforts), and 37% were dead-on arrival ED resuscitations. Only 27% of victims
      survived to become inpatients (84% died within 72 hours). Mean scene time (16.1
      +/- 7.9 minutes), transport time (9.5 +/- 5.1 minutes), and success rates for
      prehospital peripheral IV insertion (72%), endotracheal intubation (91%), and
      intraosseous line (86%) were not significantly different among those who were
      dead-on-arrival, dead-on-arrival failed resuscitations, or eventual inpatients.
      CONCLUSION: Fatal childhood injury patterns in this urban setting differed from
      reported national injury patterns. This study found a higher percentage of deaths
      from fire, gunshot wounds, and homicides but a lower percentage of motor vehicle
      related deaths. Prevention strategies need to address the injury patterns of a
      particular community. Only a small percentage of victims survived to receive
      inpatient care following their injuries, suggesting that primary prevention of
      injury may be the most effective intervention.

PMID- 8304605
TI  - Pediatric analgesia and sedation.
AB  - Sedation and analgesia are essential components of the ED management of pediatric
      patients. Used appropriately, there are a number of medications and techniques
      that can be used safely in the emergency care of infants and children. Emergency
      physicians should be competent in the use of multiple sedatives and analgesics.
      Adequate equipment and monitoring, staff training, discharge instructions and
      continuous quality management should be an integral part of the ED use of these
      agents.

PMID- 8304607
TI  - Effects of combined treatment with glycopyrrolate and albuterol in acute
      exacerbation of asthma.
AB  - STUDY OBJECTIVE: Recent reports suggest that glycopyrrolate is as effective as
      metaproterenol in the treatment of acute bronchospasm. The purpose of this study
      was to investigate whether the addition of a single aerosolized dose of
      glycopyrrolate to an albuterol regimen results in a greater improvement in
      pulmonary function than treatment with an albuterol regimen alone in patients
      with acute asthma. DESIGN: Prospective, randomized, double-blinded, controlled
      study. All patients received a total of three aerosol treatments and 60 mg
      solumedrol IV push. Patients were randomized to receive 2 mg aerosolized
      glycopyrrolate (combination therapy) or aerosolized placebo (control) in addition
      to their first 2.5 mg albuterol aerosol treatment. Both groups received 2.5 mg
      aerosolized albuterol alone for the next two treatments. SETTING: An urban
      teaching hospital emergency department. PARTICIPANTS: One hundred twenty-five
      patients with acute exacerbation of asthma were entered into the study. MAIN
      RESULTS: There was no difference in pretreatment forced expiratory volume (one
      second) (FEV1) between the control group and the glycopyrrolate group. Asthmatic
      patients receiving combination therapy had less of a change in FEV1 (52%) than
      did control patients (82%, P < .05). CONCLUSION: The combination of
      glycopyrrolate and albuterol does not appear to be beneficial over albuterol
      alone in treating patients with acute exacerbation of asthma.

PMID- 8304606
TI  - Indomethacin suppositories versus intravenously titrated morphine for the
      treatment of ureteral colic.
AB  - STUDY OBJECTIVES: To develop a protocol for the blinded IV titration of morphine
      and to compare the analgesic efficacy and side effect profile of indomethacin
      suppositories versus IV morphine in the treatment of acute ureteral colic.
      DESIGN: Randomized, double-blind, double-dummy, two-period crossover study.
      SETTING: Emergency department of a central-city, teaching hospital. PARTICIPANTS:
      Patients 18 to 75 years of age with pain suggestive of ureteral colic. Exclusions
      included pregnancy, adverse reactions to the study drugs, chronic nonsteroidal
      anti-inflammatory drug (NSAID) therapy, or any pain medicine taken within four
      hours of ED admission. INTERVENTIONS: Patients were randomized to one of two
      groups: indomethacin 100-mg rectal suppository or morphine by IV titration (5-mg
      loading dose and up to two additional 2.5-mg doses if needed). At the end of 30
      minutes, if adequate pain relief had not been obtained, treatment was crossed
      over. MEASUREMENTS: Verbal analog scale (initial pain) and visual analog pain
      relief scale. MAIN RESULTS: Seventy-five patients were entered into the study.
      Only data from those patients with stone presence confirmed by IV pyelogram or
      stone passage were analyzed. Twenty-four could not be evaluated (23 who did not
      meet criteria for stone presence and one whose pain resolved spontaneously before
      study medications could be administered). Of the remaining 51 patients, 31
      received indomethacin first and 20 received morphine first. Morphine recipients
      reported more pain relief at ten minutes (P = .02), but at 20 and 30 minutes, no
      significant difference (P = .17 and .74, respectively) existed between the two
      groups. CONCLUSION: IV morphine produced more rapid analgesia than rectally
      administered indomethacin. There were no significant differences in vital sign
      changes or number of side effects between the two treatment groups. This study is
      the first to compare an NSAID with morphine administered by IV titration,
      considered by many to be the "gold standard" for relief of acute, severe pain.
      Future studies could evaluate the simultaneous administration of an opioid
      combined with an NSAID or compare an IV titrated opioid with an IV NSAID.

PMID- 8304608
TI  - Routine admission electrocardiography in emergency department patients.
AB  - STUDY OBJECTIVES: To determine whether routine performance of an ECG could have
      been safely avoided in a subset of emergency department patients admitted to a
      university hospital. DESIGN: Retrospective consecutive case series. SETTING:
      University teaching hospital. TYPE OF PARTICIPANTS: All ED patients admitted to
      the medical service of the study hospital during a three-month period. METHODS
      AND INTERVENTIONS: Acceptable indications for an admission ECG were prospectively
      developed. Charts of all patients were reviewed to determine whether any of these
      indications were present, whether an admission ECG was performed, and whether an
      admission ECG resulted in a change in patient management or outcome. An ECG was
      classified as routine when performed in the absence of documentation of any of
      these indications. No interventions were performed. MEASUREMENTS AND MAIN
      RESULTS: There were 636 ED admissions to the medical service during the study
      period. Of the 631 patients whose chart could be located, 384 (61%) had at least
      one indication for an ECG and all but one had an ECG performed. No indications
      for an admission ECG were identified in the remaining 247 patients; of these, 202
      (82%) had an ECG performed and 45 (18%) did not. Among the 202 who had a routine
      admission ECG, the test resulted in a change in management in only three (1.5%)
      (95% confidence interval [CI], 0.3% to 4.3%) and affected patient outcome in none
      (95% CI, 0% to 1.5%). Among the 45 without indications who did not have a routine
      admission ECG, none experienced an identifiable adverse consequence during
      hospitalization (95% CI, 0% to 6.7%). CONCLUSION: The admission ECG could have
      been avoided in an identifiable subset of ED patients admitted to the medical
      service of our hospital, with no adverse effect on patient outcome. This finding,
      if corroborated in other patient populations, suggests the potential for
      significant cost savings for the US health care system as a whole.

PMID- 8304609
TI  - Circadian variation of cardiopulmonary disease onset in the general population:
      an emergency care system perspective from Berlin.
AB  - STUDY HYPOTHESIS: The objective of the present study was to determine the
      circadian pattern of onset of acute pulmonary emergencies in the general
      population and to analyze the influence of age and sex on these patterns.
      METHODS: Analysis of all 47,082 emergency calls during the years 1987 and 1988 of
      the Berlin emergency medical system. Analysis of circadian variation in incidence
      of subgroups with the leading symptom of respiratory distress, chest pain, or
      sudden unconsciousness. All cases of nontraumatic sudden death were analyzed. All
      missions were evaluated with regard to sex and age dependence. RESULTS: There is
      a circadian variation in acute cardiopulmonary emergencies with the highest
      incidence between 6 AM and noon. This applies to subpopulations of chest pain
      (9,068), respiratory distress (13,732), sudden unconsciousness (7,829),
      resuscitation attempts (4,787), and persons found dead without resuscitation
      attempts (4,780). Cases of chest pain, respiratory distress, and resuscitations
      show a second evening peak. Patients 65 years old or less have the highest rates
      in the afternoon, whereas those aged over 65 show a single morning peak (P <
      .0001). These relations are independent of sex and presenting complaint.
      CONCLUSION: Unselected populations show circadian variations in the incidence of
      cardiopulmonary emergencies. Age-related differences suggest different
      pathophysiological age-dependent mechanisms, eg, hormonal factors or lifestyle
      dependent trigger mechanisms. Emergency medical systems should adjust the
      availability of emergency services to the distinct circadian differences of life
      threatening cardiovascular and pulmonary diseases.

PMID- 8304610
TI  - Refusing care to emergency department of patients: evaluation of published triage
      guidelines.
AB  - STUDY OBJECTIVE: To determine whether a set of published triage guidelines
      identifies patients who can safely be refused emergency department care. DESIGN:
      Historical cohort study. SETTING: A public hospital ED. TYPE OF PARTICIPANTS: All
      patients triaged during a one-week period who were not in the most acute triage
      category. MEASUREMENTS: Two ED nurses, blinded to the study hypothesis, reviewed
      each triage sheet to determine whether the case met the published guidelines for
      refusing care. In addition, each ED record was reviewed for appropriateness; a
      visit was considered appropriate only if predetermined, explicit criteria were
      met and an emergency physician agreed that a 24-hour delay in care might have
      worsened the patient's outcome. MAIN RESULTS: Of the 106 patients who would have
      been refused care according to the triage guidelines, 35 (33%) had appropriate
      visits. Four were hospitalized. CONCLUSION: When tested in our patient
      population, the triage guidelines were not sufficiently sensitive to identify
      patients who needed ED care. Broad application of these guidelines may jeopardize
      the health of some patients.

PMID- 8304611
TI  - Patients who leave emergency departments without being seen by a physician:
      magnitude of the problem in Los Angeles County.
AB  - STUDY OBJECTIVES: To determine the hospital characteristics associated with
      patients leaving emergency departments prior to physician evaluation. DESIGN:
      Cross-sectional design with data collection by mail and telephone survey.
      SETTING: Los Angeles County, California. TYPE OF PARTICIPANTS: Convenience sample
      of four public and 26 private hospital EDs with a combined monthly volume of
      92,570. INTERVENTIONS: None. RESULTS: Questionnaires were returned from 83% of
      EDs surveyed. During 1990, 4.2% of patients at these EDs left without being seen
      by a physician. In all, 7.3% of public hospital patients left without being seen,
      and 2.4% of private hospital patients left without being seen (P < .001). The
      percentage of patients who left without being seen was significantly higher at
      EDs with longer waiting times, higher fraction of uninsured patients, and at
      hospitals with accredited residency training programs (P < .001 for each
      comparison). A logistic regression model, used to simultaneously evaluate the
      effects of multiple correlated factors, revealed that waiting time, fraction of
      patients uninsured, and teaching status had independent positive associations
      with patients who left without being seen. CONCLUSION: More than 4% of patients
      who seek care at EDs in Los Angeles County leave without being seen by a
      physician. A greater proportion of patients leave without medical evaluation from
      EDs with long waiting times for ambulatory patients and from those that serve
      uninsured populations. These findings should be interpreted in light of existing
      data on the health consequences faced by patients who leave hospital EDs without
      treatment.

PMID- 8304613
TI  - Emergency department: rapid identification and treatment of patients with acute
      myocardial infarction. National Heart Attack Alert Program Coordinating
      Committee, 60 Minutes to Treatment Working Group.

PMID- 8304612
TI  - Time series forecasts of emergency department patient volume, length of stay, and
      acuity.
AB  - STUDY HYPOTHESIS: Time series analysis can provide accurate predictions of
      emergency department volume, length of stay, and acuity. DESIGN: Prospective
      stochastic time series modeling. SETTING: A university teaching hospital.
      INTERVENTIONS: All patients seen during two sequential years had time of arrival,
      discharge, and acuity recorded in a computer database. Time series variables were
      formed for patients arriving per hour, length of stay, and acuity. Prediction
      models were developed from the year 1 data and included five types: raw
      observations, moving averages, mean values with moving averages, seasonal
      indicators with moving averages, and autoregressive integrated moving averages.
      Forecasts from each model were compared with observations from the first 25 weeks
      of year 2. Model accuracy was tested on residuals by autocorrelation functions,
      periodograms, linear regression, and confidence intervals of the variance.
      RESULTS: There were 42,428 patients seen in year 1 and 44,926 in year 2. Large
      periodic variations in patient volume with time of day were found (P < .00001).
      The models based on arithmetic means or seasonal indices with a single moving
      average term gave the most accurate forecasts and explained up to 42% of the
      variation present in the year 2 test series. No time series model explained more
      that 1% of the variation in length of stay or acuity. CONCLUSION: Time series
      analysis can provide powerful, accurate short-range forecasts of future ED
      volume. Simpler models performed best in this study. Time series forecasts of
      length of stay and patient acuity are not likely to contribute additional useful
      information for staffing and resource allocation decisions.

PMID- 8304614
TI  - The Oregon Health Plan: a process for reform.

PMID- 8304615
TI  - The chest pain emergency department and the outpatient chest pain evaluation
      center: revolution or evolution?
AB  - STUDY OBJECTIVE: To define the chest pain emergency department and the outpatient
      chest pain evaluation center, and to critically analyze the costs and benefits of
      modifying or replacing the current system of hospital-based evaluation of chest
      pain patients with these new systems. DATA SOURCES: Peer-reviewed articles,
      published letters, book chapters, national health statistics, and personal
      communications were used. Sources were limited to those describing experiences in
      the United States. STUDY SELECTION: Relevant sources from the United States were
      reviewed. DATA SYNTHESIS: The widespread adoption of the chest pain ED as
      currently configured would result in increased health care expenditures of
      between $389 million and $3.9 billion. It is estimated that this expenditure
      might save a maximum of 1,029 additional lives per year, at a cost of between
      $378,000 and $3.78 million per life saved. CONCLUSION: Current hospital-based
      systems for evaluating patients presenting with symptoms suggestive of acute
      ischemic heart disease need improvement. Modification of the system of initial
      patient evaluation should occur as an evolutionary change to the current ED
      system. Adoption of a formal system of chest pain EDs represents an inefficient
      use of resources. Design and implementation of patient education programs about
      ischemic heart disease should be a public sector responsibility. More research is
      needed before the proper role of the outpatient chest pain evaluation center can
      be evaluated.

PMID- 8304616
TI  - A cutaneous infection with Mycobacterium fortuitum.
AB  - We report the case of a 24-year-old man with a cutaneous Mycobacterium fortuitum
      infection. The investigation and management of this patient are discussed, and
      literature pertaining to this organism is reviewed. The importance of considering
      mycobacteria in the pathogenesis of chronic cutaneous disease is stressed.

PMID- 8304617
TI  - Emergency department use of an eye magnet for the removal of soft tissue foreign
      bodies.
AB  - We used a Ralks eye magnet (no longer manufactured) to remove magnetic foreign
      bodies in four consecutive patients with metallic soft tissue foreign bodies. In
      all four cases, the foreign body was quickly located, requiring minimal soft
      tissue exploration, time, and radiography.

PMID- 8304618
TI  - Primary mesenteric venous thrombosis: an unusual cause of abdominal pain in a
      young, healthy woman.
AB  - A 24-year-old woman presented to the emergency department with acute abdominal
      pain and a physical examination consistent with acute pelvic inflammatory
      disease. She was treated and released only to return several hours later with
      worsening of her condition and unstable vital signs. Laparotomy revealed acute
      mesenteric venous thrombosis with patent mesenteric arteries. This is an unusual
      case of mesenteric thrombosis in a young, healthy woman.

PMID- 8304619
TI  - Traumatic laceration of the ascending aorta detected by transesophageal
      echocardiography.
AB  - The diagnosis of aortic injury after blunt chest trauma is of utmost importance
      to emergency physicians. We present a case in which transesophageal
      echocardiography was successful in diagnosing a transectional intimal tear on the
      posterior wall of the ascending aorta. Potential usefulness of transesophageal
      echocardiography is discussed.

PMID- 8304620
TI  - Atraumatic rupture of utero-ovarian vessels during pregnancy: a lethal
      presentation of maternal shock.
AB  - Spontaneous rupture of utero-ovarian vessels during pregnancy is a rare cause of
      maternal and fetal loss. We report the case of a 30-year-old woman who presented
      to the emergency department in her third trimester with frank maternal shock. The
      prompt recognition of shock, correction of hypovolemia, and rapid surgical
      intervention by her obstetrician led to a favorable outcome for both mother and
      child.

PMID- 8304621
TI  - Intraosseous extravasation complication reports.
AB  - We report two cases of severe complications from intraosseous infusions. One
      child was a sudden infant death syndrome patient who developed severe tissue
      necrosis after intraosseous placement. The second child was a near drowning who
      developed a compartment syndrome requiring fasciotomy. Extravasation is a
      potentially major complication that resulted in these limb-threatening events.
      Intraosseous infusion remains an important resuscitation modality, but great care
      must be taken to avoid these results. Strategies for avoiding extravasation are
      discussed.

PMID- 8304622
TI  - Romancing the (kidney) stone.

PMID- 8304623
TI  - The emergency department and triage of nonurgent patients.

PMID- 8304624
TI  - The community as the ultimate coronary care unit.

PMID- 8304625
TI  - Evaluating patients with chest pain in the ED: improving speed, efficiency, and
      cost-effectiveness, or teaching an old dog new tricks.

PMID- 8304626
TI  - Use of fentanyl in head-injured patients.

PMID- 8304627
TI  - How to describe bullet holes.

PMID- 8304628
TI  - Spontaneous miscarriage in the ED.

PMID- 8304630
TI  - Health care leaders meet to design immunization campaign.

PMID- 8304629
TI  - HIV and bloodborne infections in emergency medicine. American College of
      Emergency Physicians.

PMID- 8304632
TI  - Defining patient comfort.

PMID- 8304631
TI  - ANA expresses disappointment over AMA opposition to APN autonomy. Interview by
      Joan Meehan.

PMID- 8304633
TI  - Understanding the primary care link to treating substance abuse.

PMID- 8304634
TI  - "I didn't really know you well enough".

PMID- 8304635
TI  - End-of-life decisions affect health care providers.

PMID- 8304636
TI  - Is primary care the answer? Nurses respond.

PMID- 8304637
TI  - AAN conference emphasizes federal measures to curb violence.

PMID- 8304638
TI  - Scientific session emphasizes impact of nursing research.

PMID- 8304639
TI  - Percutaneous transluminal angioplasty for subclavian artery stenosis.
AB  - Treatment of brachiocephalic arterial lesions by percutaneous transluminal
      angioplasty (PTA) has only recently been performed with sufficient frequency to
      allow full assessment of its value. In this series, we report our results with
      PTA of 36 symptomatic subclavian stenoses in 33 patients seen from February 1981
      through February 1992. Initial success rate was 94 per cent. There were no deaths
      and no CNS complications. Five minor complications occurred. Review of published
      surgical series suggests a similar early success rate but a significantly higher
      morbidity. These excellent early results of PTA and long-term results from other
      studies confirm that PTA of subclavian artery stenoses is a safe, highly
      effective procedure and should be considered the treatment of choice for
      symptomatic subclavian artery stenoses.

PMID- 8304640
TI  - Fungal sepsis: multisite colonization versus fungemia.
AB  - The indications for therapy and the best treatment regimens for systemic fungal
      infections are not well defined. The purpose of this study was to evaluate
      retrospectively patient management and outcome in critically ill patients with
      multiple sites of fungal colonization and/or fungemia. Medical records of 36
      fungemic patients and 76 patients without fungemia who had two or more anatomic
      sites colonized with fungal organisms were reviewed. There were 53 males and 59
      females, with a mean age of 58 years (range 15-86). Eighty-four patients (74%)
      underwent 238 operations (41% elective, 59% emergent). Gastrointestinal (37%),
      thoracic (15%), and orthopedic (13%) procedures were most common. Concomitant,
      nonfungal bacteremia was present in 56 patients (50%). Seventy-one patients (63%)
      received systemic antifungal therapy. Mortality differences between patients with
      fungemia (17/36; 47%) and fungus-colonized patients (31/76; 41%) were not
      statistically significant. Amphotericin B treatment of fungemia reduced mortality
      overall (26% vs 71%, P < 0.05) and compared with fungemic patients receiving
      other antifungals (26% vs 50%, P < 0.05). Among fungus-colonized patients,
      mortality was higher with amphotericin B than without (70% vs 36%, P < 0.05) and
      was not changed by treatment with other antifungals (37% vs 34%). Increased
      gastrointestinal operations, wound infections, and intraperitoneal fungi and
      bacteria in fungus-colonized patients receiving amphotericin B suggest that these
      patients were the most critically ill. The mortality of multisite fungal
      colonization is as high as that of fungemia. Only amphotericin B improves
      survival in fungemia. The best treatment for multisite colonization is not clear
      from the data.

PMID- 8304641
TI  - Intrahepatic vascular shunting for portal hypertension: early experience with the
      transjugular intrahepatic porto-systemic shunt.
AB  - The treatment of patients with portal hypertension and hemorrhaging varices
      remains an enigma within the surgeon's world. Many procedures have been
      described, which suggests that no general consensus exists regarding the proper
      care for these individuals. Also, these procedures usually lead to massive blood
      use and exposure to patients who have had multiple blood transfusions, thus
      posing an extreme infectious risk to the surgical team. Eight patients refractory
      to repeated esophageal sclerotherapy with advanced portal hypertension underwent
      the transjugular intrahepatic portosystemic shunt (TIPS) procedure. One other
      patient with altered anatomy underwent transjugular porto-caval shunt (TPCS)
      procedure via the caudate lobe of the liver. All procedures were successful in
      stopping esophageal hemorrhage within 6 hours of shunting. The portal-hepatic
      vein pressure gradient pre-shunt averaged 20 mm Hg, and post-shunt averaged 11 mm
      Hg. Two patients developed encephalopathy, which was controlled with medication
      and/or diet modifications. Three patients classified as Child's C-plus died
      within 1 week of their shunting procedure, and one patient, who had received
      greater than 60 units of blood, within 10 days pre-shunt, died 45 days post-shunt
      of multi-system organ failure. Four of the original nine patients are now
      classified as Child's A with active lives, eligible for transplantation without
      altered abdominal anatomy. The follow-up period is from 5 to 11 months. TIPS and
      TPCS are methods that should be considered the front-line invasive management
      techniques for patients with portal hypertension who have failed esophageal
      sclerotherapy.

PMID- 8304642
TI  - Pediatric liver transplantation in Georgia: a paradigm for the health care crisis
      in the United States?
AB  - The United States health care system, felt by many to be the most technologically
      advanced program in the world, has many critics. Two indisputable facts that
      drive such criticism are 1) inequitable access and 2) rising costs out of
      proportion to other countries. Although Georgia is a poor state and ranks
      nationally near the bottom in most measures of child and adolescent care, we
      decided to start a pediatric liver transplant program at Egleston Children's
      Hospital at Emory, Atlanta. Over the past 2 1/2 years, 18 transplants have been
      performed in 14 patients; 10 children are presently surviving. Looking carefully
      at the expenses of the first 10 patients, the average cost of orthotopic liver
      transplantation for the eight survivors was $206,375. The hospital costs for
      providing care to these 10 children were over $2 million. In a state that ranks
      49th out of 50 states in infant mortality and with nearly one-third of its pre
      school children not immunized against preventable diseases, is this a fair and
      equitable distribution of our resources?

PMID- 8304643
TI  - The role of emergent arteriography in penetrating limb trauma.
AB  - Routine arteriographic evaluation of patients with penetrating trauma in
      proximity to major limb arteries has been declining in popularity. Although some
      controversy still exists, management based on clinical examination alone has been
      advocated for those without overt signs of vascular injury. To better identify
      the need for invasive radiologic intervention, 453 limbs (394 patients)
      sustaining gunshot, shotgun, and stab wounds (331, 28, and 94, respectively) in
      proximity to a major artery underwent angiography from 1984 through 1990. An
      arterial injury was demonstrated in 37 (9.4%) of 394 limbs, with a normal
      vascular examination, but only eight (2.0%) were deemed to require operative
      intervention. By comparison, 45 (76%) of 59 patients with an abnormal vascular
      examination (diminished/absent peripheral pulses or decreased Doppler-derived
      limb blood pressures) had an arterial injury demonstrated by arteriography, with
      33 (55.9%) undergoing operative repair. The presence of an associated long bone
      fracture increased the incidence of angiographically demonstrated vascular
      injury, but operative intervention was only increased for those with an abnormal
      vascular exam. A detailed physical examination including Doppler-derived limb
      blood pressures is essential. In the presence of a normal vascular exam, routine
      arteriography for proximity of injury is unnecessary. Arteriography should be
      reserved to identify those few patients with an abnormal vascular examination and
      an unclear injury who may require vascular repair.

PMID- 8304644
TI  - Dynamic cardiomyoplasty: left ventricular diastolic compliance at different
      skeletal muscle tensions.
AB  - The possible limitation of left ventricular (LV) relaxation during diastole is a
      concern for clinicians and researchers utilizing dynamic cardiomyoplasty. This
      study was designed to evaluate the LV compliance at three different skeletal
      muscle tensions, in a normal heart and in a failing heart, created by propranolol
      infusion (11.6 mg/kg). A biventricular latissimus dorsi muscle (LDM) wrap was
      performed in 10 dogs. The LV pressure (Millar) and two minor axis dimensions
      (endocardial crystals) were measured. LV pressure-volume loops were constructed,
      and LV diastolic compliance was calculated. The measurements were obtained before
      wrap and after wrap at different LDM tensions with 0, 5, and 10 volts stimulation
      each time. These measurements were repeated after propranolol treatment. The
      results showed that LV diastolic compliance (dV/dP) was 1.79 before wrap and
      about 0.7 after wrap, and after propranolol, at various tensions and
      stimulations. LDM wrap decreased LV compliance significantly. LV compliance was
      not significantly affected by changing tension or voltage of stimulation in
      either the failing or the non-failing heart. The reduction in compliance may be
      an indication that LDM wrap causes a limitation of LV relaxation, which is one of
      wrap's deleterious effects.

PMID- 8304645
TI  - A prospective evaluation of surgically treated groin complications following
      percutaneous cardiac procedures.
AB  - During an 18-month study period, 100 noncardiac surgical complications of a
      percutaneous cardiac interventional procedure were treated at Emory University
      Hospital. These were predominantly pseudoaneurysms (61.2%), groin hematomas
      (11.2%) arteriovenous fistulae (10.2%), and external bleeding (6.1%). Less common
      complications included retroperitoneal hematomas (5.1%), arterial thromboses
      (3.1%), groin abscess (2.0%), and a mycotic pseudoaneurysm (1.0%). The
      complication rate following diagnostic catheterization was 0.6 per cent, after
      percutaneous transluminal angioplasty, 1.5 per cent, atherectomy 2.2 per cent,
      and after stent placement 16 per cent (P < 0.0001). The arterial puncture site
      was other than the common femoral artery in 34 per cent of cases. Risk factors
      for the development of complications were postprocedure anticoagulation (P <
      0.0001), female gender (P < 0.005), increased age (P < 0.0001), and small stature
      (P < 0.0001). Duplex scanning had 98 per cent accuracy in diagnosis of suspected
      groin complications, and clinical diagnostic accuracy was 77 per cent. We
      describe our technique for repair of pseudoaneurysms and arteriovenous fistula
      and discuss the possible future role of ultrasound guided compression. Mean
      hospital stay after the procedure was 3.2 days. Morbidity of surgical repair was
      21 per cent and mortality was 2.1 per cent. Groin complications following
      percutaneous cardiac procedures are related to the type of procedure performed,
      female gender, and periprocedure anticoagulation.

PMID- 8304646
TI  - Outcome of isolated pulmonary contusion in blunt trauma patients.
AB  - To determine outcome in young, healthy blunt trauma patients with isolated
      pulmonary contusion, and to identify factors associated with poor outcome, we
      reviewed 6012 consecutive adult (aged 16-49) blunt trauma admissions. Ninety-four
      (7.9%) presented with an isolated pulmonary contusion defined by chest radiograph
      and Injury Severity Score < 25; they compromise the study group. Poor outcome was
      defined as death, prolonged hospitalization (> 7 days), or a severe complication
      (pneumonia, empyema, atelectasis requiring bronchoscopy, or bronchopleural
      fistula). None of the 94 study patients died. Admission chest radiograph
      demonstrated no contusion in 34 patients (36%). Fifteen patients (16%) required
      intubation, but 13 were extubated within 48 hours. Forty-one patients (44%)
      required insertion of a chest tube, and 20 patients (21%) had a PaO2/FiO2 ratio
      of < 250 on admission. Post-injury atelectasis (n = 17), pneumothorax (n = 17),
      effusion (n = 8), pneumonia (n = 2), empyema (n = 1), and Staphylococcal
      bacteremia (n = 1) complicated hospitalizations. The following clinical factors
      were identified as predisposing to poor outcome by univariate analysis: 1)
      Pulmonary contusion on admission chest radiograph (P = 0.035); 2) Three or more
      rib fractures (P = 0.002); 3) chest tube insertion (P = 0.010) and drainage (P =
      0.020); and 4) hypoxia on admission (PO2 < 70 torr [P = .021], PaO2/FiO2 < 250 [P
      < 0.001]). Only PaO2/FiO2 < 250 on admission was an independent predictor of poor
      outcome in a multivariate analysis (P = 0.040). Our conclusion was that isolated
      pulmonary contusion in young, healthy patients is not associated with
      mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304647
TI  - Recurrent aortic occlusion.
AB  - In a review of 134 aortic occlusions in 123 patients, there were 10 patients that
      suffered recurrent aortic occlusions (RAO). These patients developed RAO after
      revascularization for primary aortic occlusion and presented with signs and
      symptoms of acute lower extremity ischemia. The recurrent occlusions occurred in
      one native aorta and in 10 aortobifemoral grafts. The etiology of the primary
      aortic occlusion included chronic aortic occlusion in eight patients and acute
      aortic occlusion and aortic graft occlusion in one patient each. Original primary
      operations performed included aortoiliac thromboendarterectomy with Dacron patch
      aortoplasty (1 patient), AF bypass (8 patients), and aortofemoral graft
      thrombectomy (1 patient). All of the grafts had end-to-end proximal anastomoses,
      the diameter of which ranged from 12 to 16 mm. Secondary operations performed for
      RAO included six axillofemoral bypasses, four redo aortobifemoral bypasses, and
      one graft thrombectomy. All patients were managed with immediate anticoagulation,
      expeditious arteriography, and revascularization. There were no perioperative
      deaths, and no limbs were lost. No patient was lost to follow-up (mean 10 years).
      Extra-anatomic bypass has proved durable. Redo aortobifemoral bypass is useful in
      selected patients with surgically correctable lesions.

PMID- 8304648
TI  - Analysis of blunt and penetrating injury of the innominate and subclavian
      arteries.
AB  - Injury to the innominate or subclavian artery is an uncommon but difficult
      management problem. Review of trauma admissions from August 1983 to August 1992
      revealed 21 patients who sustained injury to the innominate or subclavian artery.
      Eight patients sustained blunt trauma, while 13 patients sustained penetrating
      injuries. The mechanism of injury was variable, and associated injuries were
      common in both blunt and penetrating trauma. Injuries involved the right
      innominate or subclavian artery in 10 patients and the left subclavian artery in
      11 patients. Twenty patients were managed operatively. Primary repair was
      preferred for penetrating injuries, whereas a bypass graft was more common for
      blunt injuries (P = 0.41). Patients with penetrating injury were more unstable at
      presentation (admission systolic blood pressure 73 mm Hg vs 119 mm Hg, P = 0.006;
      preoperative evaluation time 66 min vs 319 min, P = 0.002) and required more
      blood transfusions (5 units vs 26 units, P = 0.007) than patients with blunt
      injuries. Mortality for the entire series was 24 per cent (0% blunt vs 38%
      penetrating, P = 0.047). Hospital days (28 vs 48) and ICU days (8 vs 14) were
      longer for survivors of penetrating injuries (P = NS). Complications were common
      in both groups. Innominate/subclavian artery injury remains a significant cause
      of mortality and morbidity.

PMID- 8304649
TI  - Crawford Williamson Long and the use of ether anesthesia.

PMID- 8304650
TI  - Calciphylaxis: early recognition and management.
AB  - Calciphylaxis, a syndrome of disseminated calcification found in chronic renal
      failure patients with secondary hyperparathyroidism, results in soft tissue
      calcification and vascular medial calcinosis leading to subsequent ischemic
      tissue necrosis. It is a rarely occurring condition in which patients present
      with painful, violaceous, mottled lesions of the extremities and/or trunk that
      progress to skin and subcutaneous tissue necrosis, non-healing ulcers, and
      gangrene. We reviewed the clinical course of seven patients (aged 24-69) with
      calciphylaxis treated at our institution over a 4-year period (October 1988-June
      1992). All seven patients underwent parathyroidectomy, with a mean time of 8
      weeks (range 3-20 weeks) between the onset of calciphylactic symptoms and
      parathyroidectomy. Four patients died, three secondary to wound-related sepsis.
      Of the three survivors, two healed soft tissue lesions primarily. The other
      required extremity amputation and wound excision before healing. Neither
      anatomical location of the soft tissue lesions nor post-parathyroidectomy serum
      calcium and phosphorus levels had any bearing on wound healing or mortality.
      Lesion severity at the time of parathyroidectomy appeared to best correlate with
      clinical course. Although treatment with phosphate-binding antacids, total or
      subtotal parathyroidectomy, and avoidance of challengers such as Vitamin D or
      local tissue trauma remain the mainstays of therapy, the uniform cure for
      calciphylaxis remains elusive. Prognosis for patients with calciphylaxis is
      dismal, even following late surgical intervention. Earlier recognition of the
      signs and symptoms of calciphylaxis should lead to timely parathyroidectomy in
      the hopes of ameliorating the symptoms and preventing or retarding its
      progressive sequelae.

PMID- 8304651
TI  - Laparoscopic Nissen fundoplication for the treatment of gastroesophageal reflux
      disease.
AB  - The Nissen fundoplication is the most common operative approach to the correction
      of gastroesophageal reflux disease (GERD) in the United States. This report
      describes our success in performing this anti-reflux procedure laparoscopically
      in 28 patients with symptomatic GERD refractory to conventional medical therapy.
      Our laparoscopic technique does not differ significantly from the traditional,
      open Nissen fundoplication. After surgery, all patients reported symptomatic
      relief, and none required medication for the control of reflux symptoms. Oral
      feedings were begun on the first postoperative day, and patients were typically
      discharged on the second day after surgery. All but two patients resumed normal
      eating within an average of 26 days. Two patients experienced longer term
      postoperative dysphagia, including one who had undergone a highly selective
      vagotomy concurrent with the antireflux surgery.

PMID- 8304652
TI  - Single lung transplantation: a temporal look at rejection, infection, and
      survival.
AB  - Single lung transplantation (SLT) has emerged as routine therapy for selected
      patients with end-stage lung disease. This study examines the incidence of
      rejection, infection, and survival during the first posttransplant year. Twenty
      one patients (12 male, 9 female; mean age 46 +/- 13 years) underwent 23 SLT
      procedures (12 left, 11 right lung). Indications were pulmonary fibrosis in six,
      emphysema in seven, primary pulmonary hypertension in three, Eisenmenger's
      syndrome in one, pulmonary veno-occlusive disease in one, a-1 antitrypsin
      deficiency in two, CREST syndrome in one, and retransplantation (graft failure
      and bronchiolitis obliterans) in two. All were maintained on triple
      immunotherapy. Survival at 1 year was 100%. The five patients with preoperative
      pulmonary hypertension had normal hemodynamics at follow up. Freedom from event
      at 1 year was rejection 23 per cent, all infections 6 per cent, viral 40 per
      cent, bacterial 55 per cent, fungal 74 per cent. At 1 year, cumulative incidence
      (events/patient-year) was rejection 1.61, all infections 2.18, viral 0.78,
      bacterial 1.12, fungal 0.28. Two of 21 patients have developed bronchiolitis
      obliterans at 1 and 2 years posttransplant. SLT provided safe, effective
      treatment for a wide variety of end-stage lung diseases. Rejection and infection,
      although common, may be safely treated with resolution.

PMID- 8304653
TI  - Human enteric infection with canine hookworms.
AB  - OBJECTIVE: To describe a zoonotic ancylostomiasis (canine), acquired from
      domestic pets by patients living in developed, urban communities. DESIGN: An 8
      year, retrospective case study. SETTING: A clinical gastroenterologic practice in
      Townsville and a university parasitology department in Brisbane, Australia.
      PATIENTS: Nine patients, each with enteric hookworm infection diagnosed by
      finding a single organism in situ; five were treated by us, and the rest were
      referred to us for parasite identification. MEASUREMENTS: Clinical and
      demographic data, complete blood examinations, total serum immunoglobulin E
      assay, and serologic testing with enzyme-linked immunosorbent assay and Western
      blot using excretory-secretory antigens of Ancylostoma caninum. Gut biopsy
      specimens were examined histologically, and hookworms were identified using
      morphologic criteria. RESULTS: The infections in three of the patients were
      diagnosed during the initial 6 years and six in the last 2 years. All owned a dog
      and described activity potentially exposing them to infection with canine
      hookworm larvae. Three patients had a laparotomy for acute abdominal pain, and
      six had colonoscopies (five with pain and one without symptoms). Six of the nine
      had blood eosinophilia (mean, 0.97 x 10(9)/L), and five of eight had elevated
      immunoglobulin E levels (mean level, 756 micrograms/L); six of eight had
      eosinophilic inflammation of the gut. In six patients, the worm was identified as
      A. caninum, whereas in three, damage to the specimen did not allow specific
      identification; however, they were unlikely to be human parasite species.
      Although all parasites were in the adult stage, none were sexually mature.
      Positive serologic findings in seven of the eight patients tested confirmed
      presence of antibody to the parasite. CONCLUSIONS: Human enteric infections with
      A. caninum are being diagnosed more frequently in northeastern Australia.
      Although infection may be subclinical, the chief symptom is abdominal pain,
      sometimes sudden and severe. The pathologic finding is focal or diffuse
      eosinophilic inflammation caused by a type 1 hypersensitivity response to
      secreted antigens. Infection by sexually immature worms is scant and nonpatent,
      indicating poor adaptation to the human host. Serologic testing assists in
      identification of occult infection. Advanced hygiene and sanitation afford little
      protection because the parasite reservoir is a large and growing pool of infected
      domestic pets.

PMID- 8304654
TI  - High-dose acyclovir compared with short-course preemptive ganciclovir therapy to
      prevent cytomegalovirus disease in liver transplant recipients. A randomized
      trial.
AB  - OBJECTIVE: To assess the efficacy of high-dose oral acyclovir therapy compared
      with preemptive, short-course ganciclovir therapy (administered only if
      cytomegalovirus [CMV] shedding occurred) to prevent CMV disease in liver
      transplant recipients. DESIGN: A randomized controlled trial. SETTING: Liver
      transplant center at a university-affiliated Veterans Affairs Medical Center.
      PATIENTS: 47 consecutive patients having liver transplantation. INTERVENTION:
      Patients were stratified by their CMV antibody status and the CMV antibody status
      of the donor and were randomly assigned to one of two treatment groups.
      Surveillance cultures for CMV (buffy coat and urine) were done every 2 to 4 weeks
      for 24 weeks in all patients. One group received high-dose oral acyclovir (800 mg
      four times daily). The experimental group received no acyclovir, but if
      surveillance cultures were positive, ganciclovir (5 mg/kg intravenously twice
      daily) was administered for 7 days. MEASUREMENTS: Cytomegalovirus shedding and
      CMV disease were measured in the two groups. RESULTS: Cytomegalovirus shedding
      before the onset of CMV disease occurred in 25% (6 of 24) of patients in the
      acyclovir group compared with 22% (5 of 23) in the experimental group.
      Cytomegalovirus disease developed in 29% (7 of 24) of the acyclovir group and in
      4% (1 of 23) of the experimental group (P < 0.05). No hematologic toxicity
      occurred with ganciclovir. CONCLUSION: Oral acyclovir is ineffective prophylaxis
      against CMV in liver transplant recipients. Preemptive, short-course ganciclovir
      therapy in patients with CMV shedding was well tolerated and provided effective
      prophylaxis against subsequent CMV disease; this protocol targets the patients at
      risk for CMV disease and minimizes toxicity and expense.

PMID- 8304655
TI  - Sleep apnea and hypertension. A population-based study.
AB  - OBJECTIVE: To measure the independent association of sleep-disordered breathing
      (sleep apnea and habitual snoring) and hypertension in a healthy adult
      population. DESIGN: A cross-sectional study of blood pressure during wakefulness
      and sleep among participants with and without sleep-disordered breathing.
      SETTING: Community-based study. PARTICIPANTS: 147 men and women, aged 30 to 60
      years, selected from Wisconsin State employees enrolled in the Wisconsin Sleep
      Cohort Study, an ongoing, prospective, epidemiologic study of sleep-disordered
      breathing. MEASUREMENTS: Sleep and medical history interview, nocturnal
      polysomnography, and 24-hour ambulatory blood pressure monitoring in all
      participants. RESULTS: Mean blood pressures were significantly higher among
      participants with sleep apnea (> or = 5 apneas or hypopneas per hour of sleep)
      compared with those without (131/80 +/- 1.7/1.1 mm Hg compared with 122/75 +/-
      1.9/1.2 mm Hg during wakefulness and 113/66 +/- 1.8/1.1 mm Hg compared with
      104/62 +/- 2/1.3 mm Hg during sleep, respectively; P < 0.05). The variability of
      the blood pressure during sleep was significantly greater in participants with
      sleep apnea or a history of snoring compared with those without (P < 0.05). After
      controlling for obesity, age, and sex, sleep apnea was significantly associated
      with hypertension in a dose-response fashion, with odds ratios ranging from 2.0
      for 5 apneic or hypopneic episodes per hour of sleep to 5.0 for 25 apneic or
      hypopneic episodes. CONCLUSIONS: Our data indicate an association between
      hypertension and sleep apnea independent of obesity, age, and sex in a
      nonselected, community-based adult population.

PMID- 8304656
TI  - Utility of selective digestive decontamination in mechanically ventilated
      patients.
AB  - OBJECTIVE: To assess selective digestive decontamination for preventing
      nosocomial pneumonia and mortality in mechanically ventilated patients. DESIGN:
      Prospective, randomized, placebo-controlled, double-blind study. SETTING:
      Respiratory intensive care unit of a 1000-bed teaching hospital. PATIENTS: 80
      patients receiving mechanical ventilation for more than 72 hours. INTERVENTIONS:
      Patients received selective digestive decontamination using polymyxin E,
      tobramycin, and amphotericin B through a nasogastric tube and also topically in
      the oropharynx; control patients received placebo. All patients received
      intravenous cefotaxime for 4 days or other systemic antibiotics if required.
      MEASUREMENTS: Bacteriologic surveillance (three times a week) was done by
      quantitatively culturing tracheal aspirates, pharyngeal swabs, and gastric juice.
      The diagnosis of pneumonia was based on quantitative cultures of protected
      specimen brush samples (> or = 10(3) CFU/mL [colony forming units/mL]) or
      bronchoalveolar lavage fluid (> or = 10(4) CFU/mL) and autopsy findings. RESULTS:
      Bronchial, oropharyngeal, and gastric colonization by gram-negative bacilli and
      Candida species was lower in the selective digestive decontamination group
      compared with the placebo group. Nonsignificant differences were found in the
      incidence of nosocomial infections (28% compared with 37%; odds ratio, 0.66; 95%
      CI, 0.35 to 1.25) and nosocomial pneumonia (18% compared with 24%; odds ratio,
      0.7; CI, 0.33 to 1.46) and in the crude mortality rate (31% compared with 27%;
      odds ratio, 1.21; CI, 0.63 to 2.34) when comparing digestive decontamination with
      placebo, respectively. CONCLUSIONS: Selective digestive decontamination in our
      mechanically ventilated patients significantly decreased the colonization rate of
      gram-negative bacilli and of Candida species but not of Staphylococcus aureus. It
      did not decrease the incidence of nosocomial pneumonia, mortality, length of
      stay, or the duration of mechanical ventilation.

PMID- 8304657
TI  - Membranous nephropathy and formaldehyde exposure.

PMID- 8304658
TI  - Hepatitis A virus-associated cholecystitis.

PMID- 8304659
TI  - The academic physician-investigator: a crisis not to be ignored.
AB  - The academic physician-investigator faces many challenges. Obtaining funding to
      support research is the greatest impediment. The National Institutes of Health,
      the single largest source of grants for the academic physician-investigator,
      approved only 14.2% of new investigator grant applications in 1990, compared with
      40% in 1965 and 1975. Physicians submitted 25% of all applications, and they have
      priority scores similar to those applications submitted by investigators with PhD
      degrees. The 14.2% funding rate for new investigator-initiated grants is
      considerably less than the 56% success rate of amended renewal investigator
      initiated grants. These trends in funding can be discouraging to the new
      physician-investigator. In addition, more emphasis is placed on clinical practice
      to generate money to support the new academic physician. These two facts, reduced
      probability of obtaining a grant and the perceived need to see more patients for
      salary support, may jeopardize retention of young faculty members. Moreover,
      training to prepare physicians for academic careers has been poor, with no
      attention given to the projected needs of the academic centers or the nation.
      This article describes the dilemma facing young physician-investigators and
      provides recommendations for improvement to the leaders of American medicine.

PMID- 8304660
TI  - The long-term therapeutic management of epilepsy.
AB  - OBJECTIVE: To provide a rational strategy for the evaluation and long-term
      management of epilepsy. DATA SOURCES: Articles written between 1964 and 1993,
      obtained from a MEDLINE search on epilepsy-related topics as well as from the
      author's personal files, major reference books on antiepileptic drugs, and
      references identified from these books. STUDY SELECTION: Articles were selected
      if they contained well-documented information comparing anti-epileptic drugs,
      represented controlled clinical trials, or were considered "key" articles of
      clinical relevance. DATA SYNTHESIS: Epilepsy is a chronic condition requiring
      careful long-term management. The treatment is complex, involving classification
      and diagnosis, selection and monitoring of the appropriate antiepileptic agent,
      and evaluation of the chosen drug's side effects and drug interactions. Because
      these side effects increase when drugs are combined, monotherapy is recommended.
      Long-term management issues and optimal drug selection differ from patient to
      patient. If seizures are not controlled by medication, the patient may have been
      misdiagnosed or misclassified. Noncompliance, a major cause of apparent
      unresponsiveness to treatment, should also be ruled out. Recognizing that current
      therapy is not ideal for many patients, new pharmacologic and surgical therapies
      are briefly discussed. CONCLUSIONS: Physicians can pursue a rational strategy for
      the management of epilepsy if they understand the risks and benefits of various
      pharmacologic and therapeutic options and if they maintain open lines of
      communication with the patient.

PMID- 8304661
TI  - The oversight of medical care: a proposal for reform. American College of
      Physicians.
AB  - The oversight of medical care, in the form of peer review, has traditionally been
      used to ensure that the highest standards of care are maintained. What is
      relatively new is the external oversight of medical practice carried out by a
      growing number of independent entities (government, third-party payers, for
      profit firms, for example), overseeing care in uncoordinated ways. Tensions arise
      when reviews of utilization and reviews of quality are conducted by different
      organizations with conflicting goals. The review instruments are still crude and
      have neither been adequately tested nor validated. Future attention to developing
      reliable and valid measures of efficiency and quality is essential. Evidence
      suggests that the principal process of review, the case-by-case review, may not
      be cost-effective and may not be conducive to improving quality. It should be
      replaced by profiles of practice patterns at institutional, regional, or national
      levels. We propose a model of oversight that emphasizes the appropriate balance
      between internal mechanisms of quality improvement and external accountability.
      In this model, internal and external reviews have specific, complementary roles
      that promote efficiency and quality. Detailed monitoring of quality and problem
      solving are left to providers who are intimately involved with care. In return,
      they become accountable to payers and the public through the surveillance of
      patterns of practice.

PMID- 8304662
TI  - When a heart stops.

PMID- 8304663
TI  - Hookworms: pets to humans.

PMID- 8304664
TI  - Hyperkalemia in elderly patients receiving standard doses of trimethoprim
      sulfamethoxazole.

PMID- 8304665
TI  - Hyperkalemia in elderly patients receiving standard doses of trimethoprim
      sulfamethoxazole.

PMID- 8304666
TI  - Hyperkalemia in elderly patients receiving standard doses of trimethoprim
      sulfamethoxazole.

PMID- 8304667
TI  - Weaning patients from mechanical ventilation using gastric pH.

PMID- 8304668
TI  - Nocturnal home oximetry in detecting the sleep apnea-hypopnea syndrome and in
      working up hypersomnolence.

PMID- 8304669
TI  - Special problems in treating tuberculosis.

PMID- 8304670
TI  - Special problems in treating tuberculosis.

PMID- 8304671
TI  - Hazard of sauna use after strenuous exercise.

PMID- 8304672
TI  - Cardiac tamponade and severe ventricular dysfunction.

PMID- 8304673
TI  - Fixed drug eruption and pseudoephedrine.

PMID- 8304674
TI  - Recapturing immediacy in morning report.

PMID- 8304675
TI  - Questions patients should ask about laparoscopic cholecystectomy.

PMID- 8304676
TI  - [Left-sidedness and functional somatic symptoms].
AB  - Since Paul Briquet's Traite Clinique et Therapeutique de l'Hysterie (1859),
      functional somatic symptoms, especially of "hysterical" nature, are said to be
      more frequent on the left side of the body. More recent studies seem to confirm
      this mostly unexplained phenomenon. Anthropology shows in numerous cultures the
      pejorative symbolism of the left. Neuropsychology suggests that the right
      cerebral hemisphere is more involved in emotions than the left hemisphere. These
      two levels of explanation must be considered together, when functional somatic
      symptoms are conceived as bodily metaphors.

PMID- 8304677
TI  - [Crisis intervention and psychiatric mortality].
AB  - Since mortality and suicide were found markedly increased in hospitalized
      psychiatric patients and may be predicted by treatment assignment, we developed a
      prospective investigation of treatment choice/mortality and suicide relationships
      in a well-assessed sample of these subjects. The overall psychiatric patients
      calling for inpatient care in a Geneva (Switzerland) 115,000 inhabitants
      catchment area within 2 months (N = 78) entered the study. During the second
      follow-up year, we found high Standardized Mortality Ratio (SMR respectively 10.5
      for overall deaths and 257.7 for suicides). Increased number and crude rates of
      suicide were associated to emergency intervention only assignment at intake.
      Suicide risk was underestimated in subjects with acute psychiatric illness, and
      should be better investigated in the future.

PMID- 8304678
TI  - [The occidental model of madness. A critical approach to the concept of
      ethnopsychiatry].
AB  - In this article the author draws out the main characteristics of the model of
      madness in the Western world. This process hinges on an approach of the
      psychopathological phenomenon within the viewpoint of cultural anthropology. The
      different cultural expressions and hermeneutic approaches to mental troubles have
      been brought out by transcultural studies, more particularly concerning
      depressions. The western model of madness lies within the history of medicine,
      this is not always the case in other cultural contexts. The question of organic
      causes has long been debated. The etiologic viewpoint of personal responsibility-
      accompanied by the notions of endogeny on the one hand and of intrapsychic
      conflict on the other--is based on the individualism which characterizes the
      Western personality and probably forms part of the make-up of guilt. The notion
      of ethnopsychiatry should therefore not be applied solely to non-Western
      practices: psychiatry as a whole should--and must--be considered as an
      ethnopsychiatry, ie a clinical and hermeneutic approach of mental trouble taking
      the culture of reference of the patient into account.

PMID- 8304679
TI  - [Self concept: toward a cognitive approach to identity disorders].
AB  - The development of the concept of self is one of the prominent facts of 20th
      century psychology; its conceptualizations are diverse. Within the field of
      cognitive psychology, concurrent with growing interest in comprehensive theories
      of personality has been the recent emergence of the self-concept. The self
      concept is viewed as the cognitive structure comprised of mental representations
      of oneself, and responsible for their integration and processing; it appears as
      the cornerstone of personality. The cognitive modelling of the self-concept
      currently opens new directions in the approach to identity processes and their
      psychopathologic disturbances.

PMID- 8304680
TI  - [Non-psychotic impairment and neurotic impairment (thoughts on the place of this
      pathology in the long-term outcome of civil servants)].
AB  - The purpose of the authors was an attempt to draw a frame of non psychotic
      patients in a invalidating process. METHOD: they analysed a population of 144
      employees from the city of Paris who had been put out of work for a long period
      of time on the basis of psychiatric impairement criteria were sociological,
      professional, life events and medical. RESULTS: the profile of this type of
      patient is likely to be a women rather than a man, she is in her forties, comes
      from a below average background, has been working for about fifteen years; the
      illness has been going on for some five years has been off work for two years,
      two out of three cases the reason is depressive pathology. The authors concluded
      neurosis invalidated more through secondary depression than through neurosis
      mechanisms.

PMID- 8304681
TI  - Detection of warble tones in wideband noise with and without hearing protection
      devices.
AB  - Noise attenuation by linear hearing protection devices (HPDs) is considered to be
      independent of the environmental noise level. Linearity of HPDs is one of the
      basic assumptions underlying the Real Ear Attenuation at the Threshold (REAT)
      method of HPD testing, which utilizes quiet conditions. However, non-linear
      growth of masking at high intensity levels may result in the effects of HPDs on
      detection of speech and warning signals being different from those at high noise
      levels. The purpose of this study was to determine if the non-linear growth of
      masking can affect detection of warble signals by persons using HPDs in wideband
      noise presented at the 100 dB(A) level. Audiometric thresholds of hearing of 10
      listeners were measured under four experimental conditions: (1) noise off, HPDs
      off (condition C1); (2) noise off, HPDs on (condition C2); (3) noise on, HPDs on
      (condition C3); and (4) noise on, HPDs off (condition C4). The results of this
      study indicate that detection of signals by persons using HPDs in noise < 100
      dB(A) can be well predicted from noise attenuation characteristics of HPDs
      measured in quiet without the need for a correction factor accommodating non
      linear growth of masking. This finding has implications for predicting the
      audibility of warning signals in noise by persons wearing HPDs.

PMID- 8304682
TI  - An evaluation of ergonomic improvements in the woodworking industry.
AB  - A survey was conducted among operators in the woodworking industry to study the
      effect of machine characteristics on exposure to mechanical load. The 28 subjects
      worked in five small factories and operated four-sided planing machines. Work
      postures and external load were analysed with the Ovako working posture analysis
      system. Among the operators awkward postures regularly occurred, such as a bent
      or twisted back (25%), outstretched arms (25%) and a twisted head (28%). The
      average percentage of time spent with lifting and carrying wooden boards and
      planks was 41%. The statistical analysis indicated that beneficial effects on
      postural load were achieved by various ergonomic improvements, such as rising
      platforms and roller paths. Work time with external load was reduced by 10% as a
      result of the presence of rising platforms and tables. The type of analysis
      presented may guide towards the improvement of work conditions of operators of
      planing machines by reducing mechanical load on the body.

PMID- 8304683
TI  - Levels of cadmium, lead and zinc protoporphyrin absorption in different risk
      groups.
AB  - We studied groups of workers, of pregnant women and of neonates exposed and
      unexposed to cadmium and lead at their place of work or in the environment. A
      total of 118 exposed and 28 unexposed workers were studied, together with 90
      exposed and 100 unexposed pregnant women and neonates. Concentrations of cadmium
      and lead in the blood were determined by atomic absorption spectrophotometry.
      There were significant differences in cadmium concentrations between workers and
      neonates, and significant differences in lead concentrations between workers and
      pregnant women. We believe these differences are due mainly to high levels of
      pollution in the area studied.

PMID- 8304684
TI  - Relevance of occupational skin exposure.
AB  - Dermal exposure gains in significance by the same token as permissible
      occupational inhalation exposures are lowered. The contribution of dermal
      absorption to the total dose absorbed during occupational exposure is apparent
      when dermal and pulmonary uptake rates are compared. Development of an
      experimental data base for evaluation and control of dermal exposure is hindered
      by: lack of suitable methods for measurement of dermal absorption in humans;
      interspecies differences in skin permeability; regional differences in absorption
      rates due to non-homogeneity of skin composition and perfusion rates over the
      body; possible skin damage induced by the chemical or dispersant; and exposure
      conditions in the workplace. In the absence of sufficient human data, theoretical
      models can provide satisfactory information on dermal absorption. It is advocated
      that the current practice of using acute dermal toxicity (LD50) as a criterion
      for warning on the potential of significant dermal absorption be replaced by a
      criterion based on comparison of the dermal penetration rate with the pulmonary
      uptake rate at inhalation exposures permissible in the workplace.

PMID- 8304685
TI  - Dermal exposure assessment techniques.
AB  - Exposure of the skin to chemical substances can contribute significantly to total
      dose in many workplace situations, and its relative importance will increase when
      airborne occupational exposure limits are reduced, unless steps to reduce skin
      exposure are undertaken simultaneously. Its assessment employs personal sampling
      techniques to measure skin loading rates, and combines these measurements with
      models of percutaneous absorption to estimate absorbed dose. Knowledge of dermal
      exposure pathways is in many cases fundamental to hazard evaluation and control.
      When the skin is the primary contributor to absorbed dose, dermal exposure
      measurements and biological monitoring play complementary roles in defining
      occupational exposures. Exposure normally occurs by one of three pathways: (i)
      immersion (direct contact with a liquid or solid chemical substance); (ii)
      deposition of aerosol or uptake of vapour through the skin; or (iii) surface
      contact (residue transfer from contaminated surfaces). Sampling methods fall into
      three categories: surrogate skin; chemical removal; and fluorescent tracers.
      Surface sampling represents a supplementary approach, providing an estimate of
      dermal exposure potential. Surrogate skin techniques involve placing a chemical
      collection medium on the skin. Whole-body garment samplers do not require
      assumptions relating to distribution, an inherent limitation of patch sampling.
      The validity of these techniques rests on the ability of the sampling medium to
      capture and retain chemicals in a manner similar to skin. Removal techniques
      include skin washing and wiping, but these measure only what can be removed from
      the skin, not exposure: laboratory removal efficiency studies are required for
      proper interpretation of data. Fluorescent tracer techniques exploit the visual
      properties of fluorescent compounds, and combined with video imaging make
      quantification of dermal exposure patterns possible, but the need to introduce a
      chemical substance (tracer) into production processes represents an important
      limitation of this approach. Surface sampling techniques provide a measure of
      workplace chemical contamination. Wipe sampling has been used extensively, but is
      susceptible to high variability. Surface sampling requires definition of dermal
      transfer coefficients for specific work activities. A preliminary dermal exposure
      sampling strategy which addresses such issues as sampling method,
      representativeness and sample duration is proposed. Despite the limitations of
      current assessment techniques, it appears feasible to consider developing dermal
      occupational exposure limits (DOELs) for selected workplaces and chemical agents.
      Initial development of DOELs would be most practical where dermal exposure is
      from surface contact primarily, and where the work closely follows a routine.
      Improvement in the techniques of dermal exposure assessment is an important goal
      for occupational hygiene research, and is likely to lead to better health for
      worker populations.

PMID- 8304686
TI  - Spatial modulation transfer function of vision by pattern visual-evoked
      potentials in patients with early glaucoma.
AB  - We applied subjective and psychophysical methods and pattern visual-evoked
      potential (VEP) P100peak latency as an objective index to measure spatial
      modulation transfer function (MTF) in normal subjects and patients with early
      primary open-angle glaucoma (POAG) in an effort to detect impairment of the
      spatial MTF of vision. To estimate spatial MTF objectively, the peak latency of
      the P100 component of pattern VEP was investigated. The mean contrast sensitivity
      in normal subjects derived from the pattern VEP peak latency was found to be
      maximum at the check size of 14.4 minutes of arc (i.e., 2.08 cycles per degree of
      spatial frequency), and the objective spatial MTF curve coincided well with that
      of the subjective one at all spatial frequencies examined. A statistically
      significant positive correlation was found between the objective (VEP) contrast
      threshold and the subjective one. Deterioration of the objective contrast
      sensitivity derived from the VEP peak latency was found to be much prominent that
      of the subjective one in patients with early glaucoma.

PMID- 8304687
TI  - Postkeratoplasty myopia treated by keratomileusis.
AB  - High myopia and astigmatism may both complicate penetrating keratoplasty and
      cause difficult problems in the visual rehabilitation of the transplanted eye.
      There are several treatment options besides contact lens fitting for high
      postkeratoplasty myopic anisometropia, including radial keratotomy,
      epikeratoplasty, minus-power anterior chamber lenses, keratomileusis, and excimer
      laser keratectomy. We present the results of keratomileusis in two patients with
      postkeratoplasty myopia. This procedure has been proved to yield favorable
      results with regard to graft clarity, refraction, and final uncorrected and
      corrected visual acuity.

PMID- 8304688
TI  - Delayed onset of bilateral acute retinal necrosis syndrome: a 34-year interval.
AB  - The case is described of a male patient who had a history of acute retinal
      necrosis (ARN) OS at age 13 years. The eye subsequently had an inoperable retinal
      detachment with residual light perception visual acuity. After a 34-year disease
      free interval, ARN developed OD that responded to medical treatment. This case
      represents the longest reported interval of ARN quiescence with eventual
      bilateral involvement and illustrates the importance of long-term patient follow
      up.

PMID- 8304689
TI  - Fluoroangiographic findings in hemodialyzed patients.
AB  - After having highlighted the main possible ocular abnormalities in patients
      affected by chronic renal failure treated with hemodialysis, we describe our
      observations in 12 hemodialyzed patients. Evaluation of the examined
      fluoroangiographic patterns was interesting because, in seven patients (58.4%),
      focal choroidal perfusion defects were found, mainly localized in the posterior
      pole and nasal portion. Similar fluoroangiographic findings have been observed in
      patients with hypertension and diabetes mellitus and anatomic and histologic
      studies have proved the existence of diabetic choroidopathy; therefore, we
      suggest that the onset of choroidopathy in hemodialyzed patients depends on an
      early arteriolar atherosclerosis of the choroidal membrane, probably secondary to
      chronic renal failure rather than to extracorporeal dialysis.

PMID- 8304690
TI  - Management of pseudophakic retinal detachment with various intraocular lens
      types.
AB  - In the last five years, 25 cases of retinal detachment (RD) after intraocular
      lens implantation were treated in the University Eye Clinic of Thessaloniki. The
      incidence of RD was lower with posterior chamber intraocular lens (PC-IOL, 0.46%)
      implantation than in the cases with anterior chamber IOL (AC-IOL, 2.6%)
      implantation. The successful reattachment rate was higher with PC-IOL (100%) than
      in cases with AC-IOL where the low success (87%) rate was caused by proliferative
      vitreoretinopathy. Therefore, the eyes with AC-IOL required reoperation more
      frequently, and the ultimate failure rate (despite multiple operations) was
      higher in the AC-IOL group. Conventional surgical techniques were used in the
      first procedure. In the reoperated cases, the most advanced techniques were used,
      such as vitrectomy combined with gas or silicone oil injection.

PMID- 8304692
TI  - Relapsing polychondritis, another cause for a "salmon patch".
AB  - We present the case of a patient with long-standing relapsing polychondritis and,
      first, an orbital mass and, then, a "salmon patch" conjunctival mass. The
      histologic pathologic findings were similar on both occasions, showing an
      inflammatory process with reactive lymphoid hyperplasia. In both situations, the
      masses responded to a short course of systemic corticosteroids. Although ocular
      inflammatory changes from relapsing polychondritis have been well described, to
      our knowledge, there have been no previous reports of conjunctival changes in the
      form of a salmon patch lesion, as described here. Relapsing polychondritis may be
      added to the differential diagnosis of a conjunctival salmon patch lesion.

PMID- 8304691
TI  - Hydroxychloroquine toxicity despite normal dose therapy.
AB  - The risk of retinopathy associated with the use of hydroxychloroquine is said to
      be nullified if the dosage recommendations are followed strictly. In this case
      report, we describe an elderly patient with rheumatoid arthritis who had
      bilateral maculopathy, presumably secondary to hydroxychloroquine therapy,
      despite a dosing regimen within therapeutic guidelines. We believe special
      attention should be given to elderly patients who are being treated with
      hydroxychloroquine because their retinal pigment epithelium may be more
      susceptible to the toxic effects of this drug.

PMID- 8304693
TI  - Retrocorneal ridges after anterior posterior radial keratotomy (Sato's operation)
      in a patient with retinitis pigmentosa.
AB  - A 51-year-old man with bilateral cataracts and retinitis pigmentosa had decreased
      visual acuity. He also had retrocorneal ridges OU. The patient had undergone
      anterior posterior radial keratotomy (Sato's operation) OU at age 14 years. We
      believe that the retrocorneal ridges in our patient, which were found after
      Sato's operation, may be rare.

PMID- 8304694
TI  - Retinal vein occlusion in Saudi Arabia: possible role of dehydration.
AB  - The medical records of 90 patients with a clinical diagnosis of retinal vein
      occlusion (RVO) who were seen at two referral hospitals in Saudi Arabia were
      reviewed. Sixty-eight (75.6%) were men. Central RVO was present in 50 patients
      (55.6%); branch RVO, in 35 patients (38.9%); and hemiretinal occlusion, in five
      patients (5.6%). Arterial hypertension was present in 43 patients (47.8%);
      diabetes mellitus, in 28 patients (31%); and preexisting glaucoma, in 26 patients
      (28.9%). The date of onset of RVO was available in 61 patients. Eighteen attacks
      (29.5%) had occurred during the month of Ramadan. The Student's t test of paired
      samples indicated that the incidence of RVO during the month of Ramadan was
      significantly higher than that of the other months of the Gregorian year. These
      findings suggest that dehydration may play a role in the pathogenesis of RVO.

PMID- 8304695
TI  - [Deafness caused by malformation of the inner ear. Current contribution of x-ray
      computed tomography].
AB  - Hearing loss due to malformations of the auditory system may involve morphologic
      abnormalities of the external canal, the middle ear, or the inner ear. Various
      combined malformations are possible. Audiologic assessment and computed
      tomography make it possible to perform a precise diagnostic evaluation of inner
      ear malformations. In a series of 71 children with congenital sensorineural
      hearing loss, 31 had computed tomographic evidence of malformations. Since 19
      children had bilateral lesions, a total of 50 ears were studied. The
      cochleovestibular abnormalities were typed and correlated to the severity and
      progression of hearing impairment. The 3 most frequently encountered
      malformations were: 1) isolated large cochlear aqueduct (n = 12), 2) large
      vestibular aqueduct (n = 8) and 3) the Mondini malformation (n = 7). The most
      severe hearing losses were associated with cochlear hypoplasia and incomplete
      cochlear segmentation. The severity of hearing impairment decreased with the
      following abnormalities in the order given: 1) large cochlear aqueduct, 2)
      Mondini malformation and 3) large vestibular aqueduct. Among the 15 patients with
      progressive hearing loss, 13 had large cochlear aqueducts either isolated or
      concomitant with other lesions. While certain evident abnormalities, such as
      cochlear aplasia or Mondini malformation, are relatively easy to diagnose, other
      more subtle morphologic changes, such as large cochlear aqueduct, still need to
      be better defined according to precise criteria for radiographic evaluation.

PMID- 8304696
TI  - [Cholesteatoma of the middle ear with closed tympanic membrane in children.
      Apropos of 8 cases].
AB  - Among 30 children with cholesteatoma undergoing surgery at the Bicetre Hospital
      between 1985 and 1990, 8 had intact tympanic membranes. Since this represents a
      larger portion of the patient population than would be expected from previously
      published data, we under-look a critical analysis of the clinical findings. Among
      these 8 cases, 2 corresponded to the criteria of congenital cholesteatoma with no
      history of otitis or trauma and 3 corresponded to acquired types with histories
      of ventilatory intubation, myringoplasty and accidental trauma. Finally, 3 cases
      were possibly of mixed origin with lesions typical of congenital epithelial rests
      and a history of commonplace era infections. Based on these observations, the
      authors review the clinical characteristics and pathogenesis of congenital
      cholesteatoma and evoke the etiologic impact of trauma, particularly iatrogenic
      events such as myringoplasty and ventilatory intubation.

PMID- 8304697
TI  - [Evoked acoustic oto-emissions in patients with diabetes mellitus].
AB  - The purpose of this study was to evaluate the cochlear function in patients with
      diabetes mellitus by analysis of evoked otoacoustic emissions (EOAE). EOAE were
      studied in 20 diabetic patients with normal hearing. The parameters used for
      analysis were the EOAE intensity and amplitude measured per 100 Hz frequency
      bands between 700 and 4000 Hz These data were compared to the data obtained in a
      group of non-diabetic control subjects with normal hearing using a Student's t
      test. The mean EOAE intensity and amplitude by 100 Hz frequency band was
      significantly lower in diabetic patients than in the control group. This seems to
      indicate the existence of an alteration in cochlear micromechanics in diabetic
      patients possibly due to changes in the functioning of the hair cells.

PMID- 8304698
TI  - [Contribution of endoscopy of the cerebellopontine angle by retrosigmoid
      approach. Neuroma and vasculo-nervous compression].
AB  - An endoscopic approach to the cerebellopontine angle has been suggested by
      several authors over the last 20 years but it is only recently that the technical
      and operative conditions for successful endoscopy could be met. The retrosigmoid
      approach provides simple and direct access to the cerebellopontine zone. The
      endoscope, with its distal light source, provides excellent illumination of a
      wide visual field within an anatomical site particularly rich in neurovascular
      structures. Endoscopic and microsurgical techniques may be combined for the
      surgical management of acoustic neuroma with the advantage of assuring better
      exposure of structures adjacent to the tumor and better control of the quality of
      dissection of the fundus of the internal auditory canal. The addition of
      endoscopic techniques, during surgery for trigeminal neuralgia or unilateral
      facial spasm, makes it possible to accurately locate the site of neurovascular
      compression without either retraction of the cerebellum or unnecessary
      dissection.

PMID- 8304700
TI  - [Mega-dolicho carotid arteries. Role of non-invasive imaging. Apropos of 3
      clinical cases].
AB  - Three cases of aberrant (elongated and tortuous) carotid arteries of the neck are
      reported. In 2 patients the carotid artery abnormalities were discovered at
      diagnostic work-up for: 1) sudden deafness, 2) persistent pharyngeal discomfort.
      Both patients presented a pulsating bulge in a pharyngeal wall with no lesion of
      the mucosa. In the third patient, the arterial abnormality was a peroperative
      discovery. All patients presented factors of risk for vascular disease. In the 2
      symptomatic patients, Doppler U.S. and magnetic resonance imaging made it
      possible to confirm the diagnosis and to eliminate other vascular or tumoral
      disorders. The indications and limitations of the various available diagnosis
      imaging procedures are assessed.

PMID- 8304699
TI  - [Cysts of the lacrimal tracts in the newborn infant].
AB  - At birth, a thin membrane often remains at the distal end of the nasolacrimal
      duct in the inferior meatus. The rupture is spontaneous during the first month of
      life. Sometimes this impatency can lead to a symptomatology usually limited to an
      uni or bilateral dacryocystitis. Exceptionally a cyst can develop in the
      nasolacrimal passageways. The authors describe three cases of intranasal
      occurrences, two of which brought about an obstructive dyspnea. Twelve cases have
      been described in the literature. This affliction predominantly occurs in young
      girls. Whenever the nasal obstruction is isolated, it is important to eliminate
      any other cause of intranasal tumor, especially an encephalocele, before any
      surgical intervention. Computerized tomographic scan is indispensable in order to
      eliminate any connection with the intracranial space. Magnetic resonance imaging
      appears promising. For the authors, the treatment must be surgical and must be
      kept simple. It consists in a cyst excision.

PMID- 8304701
TI  - [Aspergillosis of the sphenoid sinus. Apropos of 4 cases].
AB  - Aspergillosis of the sphenoid sinus is a rare entity. The authors report four
      cases of non invasive aspergillosis sinusitis, three isolated cases and one with
      nasal polyps. All cases were treated by functional endoscopic surgery. Good
      results were noted with a mean follow-up of 18 months. Frequency, clinical
      features, treatment, and etiopathogenesis of sphenoidal aspergillosis are
      discussed.

PMID- 8304702
TI  - [Malignant transformation of juvenile-type laryngeal papillomatosis].
AB  - Juvenile laryngeal papillomatosis is characterized by benign budding tumors,
      developing from the endolaryngeal epithelium. Because the evolution of these
      tumors is unpredictable, choice of the best therapy is difficult. We report two
      cases where invasive juvenile laryngeal papillomatosis, progressively colonized
      the trachea and bronchi. Malignant transformation occurred without carcinoma
      predisposing factors. In both cases patients died after pulmonary dissemination.
      We discuss the role of the human papilloma virus and the high interest of viral
      typing, for an early diagnosis of possible degeneration. The choice of the best
      therapy, chemotherapy, CO2 laser, alpha interferon or auto-vaccination will
      depend on the type on the papilloma virus.

PMID- 8304703
TI  - [Lingual rhabdomyosarcoma in an adult patient].
AB  - A case of rhabdomyosarcoma of the tongue in an adult male is reported. The
      diagnosis of this rare lesion is difficult and should be considered in every
      growing mass of the head and neck region. It is based on the pathologic
      examination of tissue samples guided by immunohistological methods. In this case
      the examination revealed an embryonal type. The tumoral progression is rapidly
      fatal unless an aggressive therapeutic regimen including surgery and radiotherapy
      is instituted. In this manner dramatic improvement in survival rate has been
      achieved in recent years.

PMID- 8304704
TI  - [Acute mountain sickness and Meniere disease].
AB  - A professional mountain guide experienced an attack of vertigo at high altitude
      (4,000 m). Clinical data and the results of functional tests, were consistent
      with an attack of Meniere's disease. The physiopathological changes noted at high
      altitudes, and known as acute mountain sickness, are described. A hypothesis is
      suggested concerning the mechanism triggering this attack of Meniere's disease at
      high altitude.

PMID- 8304705
TI  - [How to do direct laryngoscopy].

PMID- 8304706
TI  - [New pathology or new diseases? Is clinical research handicapped?].

PMID- 8304707
TI  - [Methylprednisolone versus prednisolone methylsulfobenzoate in pemphigoid: a
      comparative multicenter study].
AB  - Bullous pemphigoid is a bullous skin disease associated with basal membrane
      antibodies. At present, the first treatment of these lesions is with
      corticosteroids. In this randomized study we compared the clinical results
      obtained with methylprednisolone (MePr) in 28 patients and with prednisolone
      methylsulfobenzoate (MsPr) in 29 patients. Both drugs were administered orally in
      daily doses of 1 to 1.5 mg/kg bodyweight. Three clinical data were examined: the
      number of bullous lesions, the intensity of pruritus and the extent of erythema
      after 5 then 10 days of treatment. After 10 days, the number of bullous lesions
      had decreased by 83 p. 100 with MePr and by 78 p. 100 with MsPr, and the decrease
      of pruritus had been significantly more pronounced in the MePr group than in the
      Ms group (p < 0.05). There had been no difference between treatments in the
      regression of erythema. Altogether, good results were obtained in 22/28 patients
      under MsPr (78.6 p. 100) and 18/29 patients under MePr (62.1 p. 100). This raises
      the question of the value of pharmacokinetic studies not only with these two
      corticosteroids, but also with prednisone which seems to be better absorbed.

PMID- 8304708
TI  - [Paget disease of the vulva. 36 cases].
AB  - Thirty six patients with Paget's disease of the vulva were reviewed. The median
      age of the patients at diagnosis was 67 years (range: 45-91 years). One patient
      had a history of previous mammary adenocarcinoma. Screening for malignancy
      revealed two colonic tumours. Two patients with negative screening at
      presentation developed, 12 and 18 months respectively after vulvectomy, an
      ovarian carcinoma stage IIc and a cervical and urethral adenocarcinoma. All
      patients were treated by surgery based on extent of the disease. The operations
      performed included total vulvectomy (n = 11), partial vulvectomy (n = 14) and
      wide local excision (n = 4). Out of the 36 patients, 29 were available to follow
      up. The median follow-up period was 74 months (range 2-204 months). Three
      patients died of metastatic disease due to vulval adenocarcinoma and breast
      carcinoma, or of liver metastases from an unknown adenocarcinoma. Eighteen of the
      29 patients followed up remained free of disease. Five out of the 16 patients
      with positive margins recurred, as did 5 out of 9 patients with negative margins.
      Treatment of Paget's disease of the vulva is surgical. In order to prevent
      recurrence, some authors have proposed surgical excision extending beyond the
      visible clinical lesions with intraoperative frozen sections. The data we
      recorded show that free margins do not seem to correlate with recurrence, so that
      large excision beyond the clinical lesion is not useful.

PMID- 8304709
TI  - [Interleukin-2 immunotherapy and cutaneous manifestations].
AB  - The cutaneous manifestations which follow the administration of recombinant
      interleukin-2 (rIL-2) are well known, but their nature and severity have not yet
      been fully studied. The authors report the dermatological changes observed in 12
      patients treated with rIL-2 for renal cancer. The predominant lesion was
      generalized erythema followed by desquamation.

PMID- 8304710
TI  - [Loose anagen hair syndrome].
AB  - A typical case of loose anagen hair syndrome in a 4-year old girl is reported
      here. The key signs of this disease are the absence of hair cut since infancy, an
      easy and painless uprooting of the hairs and a 100 p. 100 anageneity of the hairs
      with distorted bulbs on trichograms. There is no known treatment of this anomaly.
      Cosmetically, the course of the disease is usually favourable, but abnormal
      trichograms and fragility of the hairs persist in adulthood. A brief review of
      the literature concerning this probably underestimated condition is presented.

PMID- 8304711
TI  - [Costa acro-kerato-elastoidosis].
AB  - We report 2 cases of acrokeratoelastoidosis of Costa observed in two sisters born
      of unaffected first cousins. The lesions were lenticular papules, either white or
      of normal skin colour, which were isolated or arranged in groups of plaques
      crossed by the natural furrows and located on the thenar eminences, the lateral
      edges of the hands and fingers and the back of the interphalangeal joints. On the
      feet, the lesions, located on the lateral edges, the plantar arch and the heel,
      were much more keratotic and appeared to be translucent. Hyperhidrosis was noted
      in only one of the two patients. Histological examination showed, beneath an
      acanthotic and hyperkeratotic epidermis, a reduced elastic network with shorter
      and thinner fibres in the middle dermis. These are two typical but rough cases of
      acrokeratoelastoidosis of Costa. The mode of transmission of this disease
      (autosomal recessive?) seems to be unusual compared with the data found in the
      literature (dominant, or sporadic cases).

PMID- 8304712
TI  - [Cutis verticis gyrata: reduction surgical treatment].
AB  - Cutis verticis gyrata (CVG) is a rare cause of acquired scalp thickening; in its
      primary form, the disease does not show any bone involvement. A 19-year old man
      had noticed a moderate thickening of the scalp at the age of 15. He progressively
      developed ridges and furrows in the occipital and parietal areas: after a four
      year period, there were ten sagittal and irregularly parallel folds. There was
      neither pain nor pruritus, and the hair had a normal appearance. Complete
      neurological examination was unremarkable and the patient was of normal
      intelligence. All biological investigations, including STH and TSH levels, were
      normal. X-ray examination and tomodensitometry did not show any bone involvement.
      Our patient was treated by surgical reduction of the scalp areas involved under
      general anesthesia, with a very good result. This is a typical case of primary
      CVG. Differential diagnosis of primary cutis verticis gyrata comprises
      pachydermoperiostosis, cerebriform intradermal nevus and many secondary
      conditions associated with hypertrophy and folding of the scalp. A relatively
      simple surgical treatment results in a major reduction of the scalp thickening,
      and avoids maceration.

PMID- 8304713
TI  - [Spontaneous ecchymosis disclosing acquired factor VIII inhibitor].
AB  - An 81-year old woman suddenly developed extensive ecchymosis. A factor VIII:c
      inhibitor was detected. She received porcine factor VIII, corticosteroids,
      intravenous immunoglobulins and cyclophosphamide. Normalization of factor VIII
      level was achieved in 1 month. The patient died, 3 months later, of congestive
      heart failure. Spontaneous development of factor VIII inhibitors is an extremely
      rare event which usually occurs in dramatic bleeding. Many associated diseases
      have been reported. Patients with serious bleeding should be given porcine factor
      VIII. Immunosuppressive therapy consists of corticosteroids, cyclophosphamide and
      intravenous immunoglobulins.

PMID- 8304714
TI  - [Fenofibrate photoallergy].
AB  - Photosensitization to lipid-lowering fibric acid derivatives are rare. We report
      a case of photoallergy induced by fenofibrate, proved by a positive UVA photo
      patch-test. Evolution towards persistent photosensitization is probable, since
      photobiological abnormalities persisted during four months after fenofibrate was
      discontinued. The fact that patch-tests to various benzophenones were negative is
      not in favour of the benzophenone group being responsible for the
      photosensitization reaction.

PMID- 8304715
TI  - [Focal epithelial hyperplasia. An unusual clinical aspect].
AB  - We report a case of focal epithelial hyperplasia in a child born in France of
      Algerian parents. The clinical appearance was unusual in that certain lesions
      were verrucous and pediculate. A virological study revealed the presence of
      papillomavirus 32, one of the two types of HPV specifically associated with this
      entity.

PMID- 8304716
TI  - [A case for diagnosis: cutaneous metastasis of breast carcinoma].

PMID- 8304717
TI  - [Capsaicin in dermatology].

PMID- 8304718
TI  - [Treatment of cutaneous ancylostoma larva migrans].

PMID- 8304719
TI  - [Prevention of cutaneous carcinoma with retinoids. Question of the month].

PMID- 8304720
TI  - Assessing test accuracy and its clinical consequences: a primer for receiver
      operating characteristic curve analysis.

PMID- 8304721
TI  - Urinary growth hormone measurements in children with renal insufficiency.
AB  - It has been reported that intrinsic renal factors could affect urinary growth
      hormone (UGH) measurements. We compared UGH excretion in 21 children aged 4-16
      years, with various degrees of renal insufficiency, with that in 10 control
      subjects aged 5-13 years. We found 100- to 1000-fold elevations in UGH in
      children with plasma creatinine concentrations > 120 mumol/L (Group A) compared
      with patients with plasma creatinine concentrations < 120 mumol/L (Group B) and
      control subjects. UGH excretion (microU) in the three groups was as follows:
      group A 804-8556 (median 2649); group B 1.0-85 (median 7.5); and controls 2.6-7.3
      (median 4.0). Elevated urinary beta 2-microglobulin levels (microgram) were also
      observed in group A patients: 875-15,400 (median 11,637) as compared with group
      B, 1.0-104 (median 32) and controls, 3-18.7 (median 8.0). There was no
      significant difference in albumin excretion between groups A and B through six
      patients in group B with nephrotic syndrome (NS) excreted significantly more
      albumin (P < 0.05) than the other 15 patients investigated. Our data show that
      abnormalities of renal function have a profound effect on growth hormone
      excretion and we suggest proximal tubular dysfunction as the causative factor. We
      conclude that UGH measurements do not provide a reliable means of assessment of
      hypothalamo-pituitary function in patients with renal insufficiency.

PMID- 8304722
TI  - Serum ultrafiltrable copper, total copper and caeruloplasmin concentrations in
      gynaecological carcinomas.
AB  - Serum copper and caeruloplasmin concentrations are elevated in various
      carcinomas, but it is not known whether the rise in serum copper is due to
      elevation of caeruloplasmin alone or whether it is also due to the elevation of
      'free' copper. We therefore determined ultrafiltrable copper to answer this
      question. Serum ultrafiltrate was prepared using the Amicon micropartition system
      and ultrafiltrable (free) copper was determined by flameless atomic absorption
      spectrophotometry. Serum total copper was determined by flame atomic absorption
      spectrometry and caeruloplasmin by rate nephelometry. There was no significant
      difference in the ultrafiltrable copper concentration between patients with
      gynaecological tumours and control subjects. However, total copper and
      caeruloplasmin concentrations were significantly elevated in cancer patients
      compared with control subjects. In contrast to total copper and caeruloplasmin
      concentrations, ultrafiltrable copper concentrations showed no significant
      increase with increase in the stage of the cancer.

PMID- 8304723
TI  - Clinical associations of an increased transthyretin band in routine serum and
      urine protein electrophoresis.
AB  - The 9697 electrophoretograms performed over an 8 year period were reviewed to
      identify the frequency and clinical associations of the finding of a prominent
      transthyretin band in serum or urine, the concentration of which was equal to or
      greater than a 64 mg/dL protein calibrator. All samples were electrophoresed at a
      constant 90 V using agarose gels with a barbital buffer pH 8.6 and Ponceau S
      staining. Reference calibrators were used as standards to identify increased
      transthyretin bands and the patients' clinical records were subsequently
      reviewed. High values were found in 46 patients' sera and a further nine
      patients' urines representing 0.57% of the total workload. Renal impairment was
      present in 58% of cases including those with chronic renal failure, the nephrotic
      syndrome and paraproteinaemia. The high levels were not persistent in three
      myeloma cases where there was a recovery in renal function following
      chemotherapy. In some nephrotics, a high urine transthyretin may be secondary to
      a general hepatic albumin and transport protein synthesis response to severe
      proteinuria. Why the serum transthyretin was elevated in many other cases remains
      unclear.

PMID- 8304724
TI  - Reducing the cost of phenytoin assays with in-house TDx reagents.
AB  - The Abbott TDx is frequently used for therapeutic drug monitoring of phenytoin
      concentrations, but reagent costs are high. In an attempt to reduce these costs,
      we investigated the preparation of in-house reagents. A commercial antiserum was
      available at reasonable cost and the fluorescent tracer was easily prepared. We
      describe the preparation of these reagents and their application to the TDx
      system. Substantially reduced costs were obtained using the in-house reagents.

PMID- 8304725
TI  - Proteolytic activity and free amino acid concentrations in polymorphonuclear
      leucocytes.
AB  - Polymorphonuclear granulocytes (PMN) are valuable tools for evaluating amino acid
      (AA) metabolism in nucleated cells, although variations of free amino acid
      concentrations due to the methods used for the separation of the cells and the
      procedures used for lysis have been reported. Furthermore, analytical variations
      in PMN AA concentration may be induced by protease activation during preparation,
      so that free AA detected in cells could originate from proteolysis other than
      from the physiological metabolic pathways and transport systems. To study this
      possibility we measured granulocyte protease activity and AA concentrations in
      cell suspensions processed with and without the addition of antiproteolytic
      agents. Granulocyte AA concentrations and protease activity in samples treated
      with antiproteolytics were 8-15 times lower than in samples processed without
      antiproteolytics. The use of protease inhibitors throughout the sample
      preparation is necessary for reliable estimation of free AA in granulocytes.

PMID- 8304726
TI  - Avidin-biotin based electrochemical immunoassay for thyrotropin.
AB  - A two site electrochemical enzyme immunoassay for thyrotropin (TSH) has been
      developed. This assay is based on the use of an immobilized capture antibody and
      a biotinylated second antibody. Detection is achieved via avidin labelled with
      alkaline phosphatase. The substrate 1-naphthyl phosphate was used and the product
      1-naphthol was detected at disposable screen-printed carbon 8-electrode combs
      using specially designed instrumentation.

PMID- 8304727
TI  - Immunoturbidimetric measurement of low concentrations of apolipoprotein B in
      lipaemic samples.

PMID- 8304728
TI  - Reduced bioavailability of cyclosporin A capsules in a renal transplant patient
      with partial gastrectomy and ileal resection.

PMID- 8304729
TI  - Glycated haemoglobin.

PMID- 8304730
TI  - Is it necessary to alkalinize urine samples for measurement of retinol binding
      protein?

PMID- 8304731
TI  - Index of individuality and utility of population based reference range.

PMID- 8304732
TI  - [Meaning of the form and facial dysmorphism].
AB  - Face morphogenesis and its troubles disturb always the patient and its family.
      Why? Among the ways of research about these problems the Catastrophe Theory of R.
      Thom is helpful. In another way the terms and words used to explain the lesions
      and the troubles of self-perception are examined.

PMID- 8304733
TI  - [Historical cases of facial hypertrophy of various etiologies].

PMID- 8304734
TI  - [Esthetic reconstruction of the face in burnt patients].
AB  - All reconstruction should be aesthetic but in burned patient, everything combines
      to make a cosmetically satisfactory result more difficult to achieve. However the
      burns patients, deformed and disfigured has to confront the gaze of others in
      daily life. Three points are discussed by authors: skin quality can be improved
      or replaced by a full thickness pressure graft; surgical modification of the
      underlying structures; repair of peri-orificial areas and free edges.

PMID- 8304735
TI  - [Which diagnosis? Apropos of hemifacial hypertrophy].

PMID- 8304736
TI  - [Extra-periosteal mask-lift. Technical note].
AB  - Based on the work by Caix and Goin, it seemed logical to perform mask-lift by
      extra-periosteal dissection, as it is the adipose and cutaneous planes which are
      affected by age, while the periosteum is not distended. It is much more logical
      to directly displace the planes concerned by the operation rather than operating
      underneath the periosteum, a relatively poorly extensible barrier. Apart from the
      dangerous zone of the middle third of the zygoma, the frontal branch of the
      facial nerve is at no greater risk than during a forehead facelift. Extra
      periosteal dissection does not raise any particular problems in the malomaxillary
      region.

PMID- 8304737
TI  - [Titanium plates for mandibular reconstruction and radiotherapy].
AB  - Mandibular reconstruction plates are now used after cancer surgery in particular
      patients. This study assesses the irradiation of Titanium mandibular
      reconstruction plates in terms of both dosimetry and mid-term tolerance. Twenty
      patients with mandibular plates underwent radiotherapy (mean dose 60 Gy). The
      radiation dose on the patient itself was calculated with 3-dimensional treatment
      planning. A clinical and radiological evaluation of tolerance was made 6 months
      after the end of the treatment: intraoral and cutaneous healing and possible
      osteomyelitis. Mid-term tolerance was very satisfactory with only two failures at
      6 months. When using parallel opposing fields, the overdosage into tissues was
      reduced to approximately 5 p. cent; and radiotherapy has probably no effect on
      titanium plate tolerance.

PMID- 8304738
TI  - [Lingual schwannoma. Apropos of 2 clinical cases].
AB  - In the light of two cases of benign schwannomas of the tongue, including one
      particularly large tumour, the authors review the clinical and histological
      features and natural history of these tumours. Their rarity may explain the
      limited knowledge concerning these tumours and the long interval prior to
      treatment, resulting in technical difficulties due to their volume. Surgical
      enucleation is generally easy to perform. The prognosis is excellent after
      resection, as malignant transformation is exceptional.

PMID- 8304739
TI  - [Resectable tumors of the peripheral nerves. Apropos of 73 nerve tumors in 53
      patients].
AB  - The authors report on a study of 53 patients suffering from resectable nerve
      tumors of the peripheral nerves, representing a total of 73 tumors. This concerns
      a round, hard swelling, with slight transversal movement, located along the
      course of a nerve. This swelling was painful and percussion led to lancinating
      pains along the course of the nerve. The same surgeon operated on all of these
      patients. The surgical treatment of the 46 patients undergoing surgery for the
      first time always consisted in a simple enucleation after opening of the
      epineurium with good results. Seven cases were seen in the stage of sequelae and
      five were clearly improved by a second operation. The principal surgical
      procedures are given. The maximum time of follow-up was 14 years and the minimum
      12 months, with an average of 52 months. Our study included 34 women and 19 men
      suffering from one or more nerve tumors. The average age was 50.7 years, ranging
      from 17 years to 88 years. 39 patients had schwannomas, 1 lymphoma of the sciatic
      nerve, 2 hemangiomas of the sheath of Schwann, 6 intraneural cysts and 5
      fibrolipomas. The authors analyse the diagnosis difficulties, the additional
      examinations and particularly RMI which has been perform on 7 patients and
      revealed to be very sensitive and of a great liability.

PMID- 8304740
TI  - [Surgical classification of the upper limb in tetraplegic patients].
AB  - The authors report the classification which they use in functional surgery of the
      upper limb in tetraplegics. They have adopted an international surgical
      classification and have added minor modifications which they justify. High,
      intermediate and low tetraplegias must be distinguished. They form homogeneous
      groups requiring different surgical modalities. They authors emphasise the
      schematic nature of this classification which can only be used as a guide for
      surgical indications, as each case must be assessed individually.

PMID- 8304741
TI  - [Musculocutaneous flap of latissimus dorsi in breast reconstruction. Results of a
      series of 163 cases].
AB  - One-hundred and sixty-three consecutive latissimus dorsi myocutaneous flap breast
      reconstructions performed after modified radical mastectomy between 1982 and 1991
      were reviewed. Patients were followed for an average of 4.7 years after
      reconstruction. Satisfactory result was obtained in the majority of cases.
      Surgery of the opposite breast was performed on 1/3 patients of the initial
      group. Peri-operative and long term complications, of which capsular contracture,
      are reviewed and appeared infrequent. Latissimus dorsi myocutaneous flap breast
      reconstruction usually mit patient expectations, with a minimum of procedures and
      low morbidity.

PMID- 8304742
TI  - [Reduction mammaplasty according to McKissock's technique. A review of 312
      cases].
AB  - 312 cases of reduction mammaplasty performed over a period of 12 years according
      to McKissock's technique are reviewed. This technique is characterised by a pre
      established drawing, a vertical nipple-bearing bipedicle flap, and perfectly
      defined cutaneo-glandular resection according to three blocks. it is indicated in
      almost 70% of women between the ages of 20 and 50 years with an equal
      distribution by 10-year age-groups. The remaining 30% are equally divided between
      women under the age of 20 years and women over the age of 60 years. Reduction
      mammaplasty is performed after menopause in 30% of cases. Maintenance of the
      results at two years and projection of the ANC are perfectly satisfactory. On the
      basis of these cases, secondary ptosis does not appear to be more severe with
      this technique and secondary glandular resorption is also unlikely. No necrosis
      of the ANC was observed in this series. In conclusion, this technique achieves
      aesthetic symmetrical breasts with long scars under very good conditions of
      safety. Shortening of the scars could only be achieved to the detriment of the
      shape of the breasts.

PMID- 8304743
TI  - [Contribution of polyurethane dressing in mammary reconstructive surgery].
AB  - The authors report the use of a new polyurethane dressing, studied in 20 patients
      undergoing breast surgery. Based on objective criteria, this study analyses the
      contribution of this dressing in the postoperative course.

PMID- 8304744
TI  - [Principles of palliative motor surgery of paralysis of the hand].
AB  - The purpose of surgical restoration of the paralysed hand is to use or to
      reconstruct the physiological tenodesis effects which are linked on to flexion
      extension motions of the wrist. Active movements of interphalangeal (IP) flexion
      and metacarpo-phalangeal (MP) extension of the fingers are made by extrinsic
      muscles coming from the forearm. The intrinsic muscles of the fingers produce MP
      flexion and IP extension. A claw deformity occurs when they are completely
      paralysed in a finger whose joints are flexible, and whose extrinsic muscles
      remains functional or are restored. When Bouvier's maneuver is positive, the claw
      is said simple, and its treatment is either MP capsuloplasty when there is no
      motors, or an active palliative procedure with proximal (or MP) effect when
      motors exist: lasso and/or direct interosseous activation. Indications of the
      classical active palliative procedures with distal (or IP) effect remain rare,
      only in a few complicated claw deformities. Circumduction of the thumb may be
      decomposed into three elementary movements: reposition, antepulsion, and
      adduction, which are respectively controlled by the radial, median, and ulnar
      nerves. Each of these movements may be restored by a specific tendinous transfer.
      In the total paralysis of the thumb as we observe in high tetraplegia, a key-grip
      may be restored by joint stabilization of the thumb, associated with activation
      of the Flexor Pollicis Longus and Extensor Pollicis Longus by means of tenodesis
      or tendinous transfers.

PMID- 8304745
TI  - [Urodynamics of the lower tract. Introduction].

PMID- 8304746
TI  - [Techniques of urodynamic diagnosis. Measurement--pressure--flow].
AB  - The urodynamic techniques useful for the diagnostic assessment of
      vesicosphincteric disorders are uroflowmetry, measurement of abdominal, urethral
      and vesical pressure and electromyography. Uroflowmetry is a very widely used
      screening examination, as it is atraumatic. Other techniques are more invasive,
      but provide more pathophysiological information. The methodology is recalled for
      each of these examinations. The parameters to be analysed are described in
      detail. The value and limitations of these modalities are emphasised. Combined
      examinations allow a better understanding of vesicosphincteric equilibria and
      disequilibria and reveal the concepts of compliance, detrusor pressure, isometric
      detrusor contractions, hyper and hypoactivity, and pressure transmission.

PMID- 8304747
TI  - [Uroradiology].
AB  - Radiology of the urinary tract has a great place in evaluating voiding
      dysfunction. The role of the radiologist is not limited to diagnosis of the
      sequelae of voiding dysfunction but he must provide information about causes,
      mechanisms and helps to provide a more accurate diagnosis. Projectional
      radiography (excretory urography, voiding cysto-urethrography) is still the best
      method of evaluation in spite of development of new imaging techniques
      (ultrasonography, computerized axial tomography, magnetic resonance imaging).
      Radiodynamic examination of the lower urinary tract is the best method of choice
      to study the complex functional problems involving those structures.

PMID- 8304748
TI  - [Electrodiagnosis in urinary pathology].

PMID- 8304749
TI  - [Infravesical obstruction].
AB  - Infravesical obstruction presents clinically in the form of dysuria. Urodynamic
      studies play an important role to distinguish between a disorder of detrusor
      contractility and a functional or organic obstruction. The value of uroflowmetry,
      static and voiding urethral pressure profiles, cystometry and electromyography is
      discussed. The instantaneous voiding profile appears to be the most useful test:
      it allows calculation of urethral resistance, which is the ratio between bladder
      voiding pressure and the square of flow. Bladder neck obstruction is present in
      more than 80% of cases with a value greater than 0.5. Obstacles are more easily
      identified clinically in women, but the same tests can be applied with a poorer
      reliability for urethral resistance.

PMID- 8304750
TI  - [Factors of female urinary incontinence].
AB  - The history, physical examination and complementary investigations must be
      directed towards analysis of the multiple factors responsible for urinary
      incontinence, whose relative roles differ from one patient to another. Treatment
      is primarily directed towards factors which are the easiest to correct. Urethral
      and vesical factors are summarised in this brief introductory article.

PMID- 8304751
TI  - [Evaluation of factors of female urinary incontinence and therapeutic
      indications].
AB  - A good understanding of the factors involved in female urinary incontinence is
      essential for the therapeutic management of incontinent women. Urinary stress
      incontinence involves three variables which participate in the pressure
      equilibrium during effort: mobility of the urethrovesical junction, urethral
      resistance and the intensity of effort. The most appropriate treatment for each
      patient can only be selected by investigating all three of these factors and by
      determining their respective roles in incontinence. Urge incontinence is also
      multifactorial, but, very often, no cause can be found on the aetiological
      assessment, leading to the diagnosis of idiopathic instability. The factors of
      detrusor motor instability are discussed and their aetiological treatment is
      proposed.

PMID- 8304752
TI  - [Treatment of male incontinence].
AB  - Male urinary incontinence may be due to a variety of pathophysiological
      mechanisms: detrusor hyper- or hypoactivity, lower obstruction and, most
      frequently, sphincter incompetence, generally secondary to surgery. As far as
      possible, treatment should be aetiopathogenic, with the use of drugs for detrusor
      dysfunction. The treatment of sphincter incompetence primarily consists of
      prophylaxis and education of urologists. When a lesion does not resolve with
      time, i.e. after more than one year of physiotherapy or drugs, the artificial
      sphincter may be indicated with good results in more than 90% of cases.

PMID- 8304753
TI  - Paracrystalline surface layers of dairy propionibacteria.
AB  - We examined 70 dairy propionibacteria and detected a crystalline surface layer (S
      layer) in only 2 organisms (Propionibacterium freudenreichii CNRZ 722 and
      Propionibacterium jensenii CNRZ 87) by freeze-etching and sodium dodecyl sulfate
      polyacrylamide electrophoresis (SDS-PAGE). Both S-layers exhibited oblique (p2)
      symmetry (a = 9.9 nm; b = 5.4 nm; gamma = 80 degrees) and completely covered the
      cell surface. Treatment for 15 min at the ambient temperature with 5 M guanidine
      hydrochloride or acidic conditions (250 mM ammonium acetate, pH 2.7) efficiently
      extracted the S-layer protein from intact cells of strain CNRZ 722, whereas
      treatment with 5 M guanidine hydrochloride at 100 degrees C for 15 min was
      necessary to isolate the S-layer protein of strain CNRZ 87. The precipitates
      obtained after dialysis of the extracting agents produced no regular patterns.
      The molecular masses of the two S-layer proteins, as estimated by SDS-PAGE, were
      58.5 kDa for the strain CNRZ 722 and 67.3 kDa for the strain CNRZ 87. Mass
      spectrometry of the isolated S-layer protein of strain CNRZ 722 gave a molecular
      mass value close to the expected value (56,533 Da). The N-terminal sequences of
      the two purified S-layer proteins differed, as did their amino acid compositions,
      except that the same high hydrophobic amino acid content (52%) was observed.

PMID- 8304754
TI  - The labial-ala transposition flap.

PMID- 8304755
TI  - Are dermatologists greedy?
AB  - Are dermatologists greedy? A better question: are doctors greedy? The most
      relevant question is this: why is the subject of physician greed ignored by
      organized medicine? Certainly, the public talks about physician greed. "Fraud and
      Abuse Are Milking Medicare" runs the headline in a recent magazine article that
      featured the subtitle, "Dermatologists Removes a Simple Growth and Bills for
      Multiple Growths." The question remains: why, despite the present uproar over
      escalating medical care costs, does the medical profession fail to engage the
      issue of inappropriate reimbursement? This article explores some of the reasons
      and possible remedies for our diffidence.

PMID- 8304756
TI  - p53 oncoprotein expression and proliferation index in keratoacanthoma and
      squamous cell carcinoma.
AB  - BACKGROUND AND DESIGN: Whether solitary keratoacanthoma (KA) is a malignant
      neoplasm despite its self-limited clinical behavior, and the distinction between
      KA and squamous cell carcinoma (SCC) are related aspects of a long-standing
      debate among dermatopathologists. Recent advances toward understanding the
      molecular basis of malignant transformation may allow this issue to be resolved.
      Mutant p53 tumor-suppressor protein has been shown to accumulate in cutaneous SCC
      and other tumors, and may be a relatively specific marker of malignancy. We
      studied 20SCCs, 20KAs, and an additional 10 regressing KAs (rKA) by
      immunohistochemistry for the expression of p53 protein. Since p53 is believed to
      play a pivotal role in the regulation of cell division, we also quantitated
      proliferation in the tumors by examining Ki-67 antigen expression. RESULTS:
      Sixteen (80%) of the KAs showed nuclear staining with anti-p53 antibody,
      distributed along the outermost layers of the aggregates of neoplastic cells,
      while 12 (60%) of the SCCs were p53 positive. Eight (80%) of the rKAs also showed
      p53 positivity. Mean Ki-67 proliferation fraction was higher for KA than for SCC
      (55% vs 46%), but this difference was not statistically significant. p53
      Expression did not correlate with the grade of SCC. CONCLUSIONS: A majority of
      KA, rKA, and SCC contain stainable quantities of p53 protein, supporting the view
      that KA is a type of regressing SCC.

PMID- 8304757
TI  - Overexpression of p53 tumor suppressor protein in porokeratosis.
AB  - BACKGROUND: p53 is a tumor suppressor nucleoprotein. Mutations of the p53 gene
      have been found in a variety of malignant neoplasms. Wild-type p53 has a short
      half-life, possibly only 20 to 30 minutes, and is not present in the nucleus at
      levels that are detectable with routine immunohistochemical techniques. Mutant
      p53 has a longer half-life, and is readily detectable with immunoperoxidase
      staining. RESULTS: We studied 17 specimens from patients with either
      porokeratosis of Mibelli or actinic porokeratosis, using immunoperoxidase
      staining with an antibody directed against the p53. There was staining of
      lesional keratinocyte nuclei in 16 of 17 specimens, limited in most cases to the
      zone between cornoid lamellae. Staining for proliferating cell nuclear antigen
      was increased above background levels in only six of 13 specimens. CONCLUSIONS:
      The finding of p53 immunoperoxidase staining in porokeratosis suggests genetic
      mutation, as occurs in other cutaneous keratinocytic neoplasms, and the lack of
      corresponding proliferating cell nuclear antigen expression in many specimens
      indicates that p53 overexpression is not simply a reflection of increased
      cellular proliferation.

PMID- 8304758
TI  - Profound deficiency in normal circulating T cells in erythrodermic cutaneous T
      cell lymphoma.
AB  - BACKGROUND AND DESIGN: To accurately assess tumor burden in cutaneous T-cell
      lymphoma as well as to determine the number of residual normal circulating T
      cells, it is necessary to accurately distinguish malignant cells. Because
      cutaneous T-cell lymphoma cells regularly display many normal phenotypic markers
      of T cells (CD2+, CD3+, CD4+) these surface proteins have been of limited value.
      We have used a set of monoclonal antibodies with specificity for those T-cell
      receptor proteins containing variable regions on the beta chain to distinguish
      normal from malignant T cells in patients with cutaneous T-cell lymphoma.
      RESULTS: The results revealed an unanticipated and profound expansion of the
      malignant cell populations (59% to 87% of blood T cells) in six patients with
      total T-cell counts in the normal or near normal range. By subtracting the
      percentages of malignant T cells, identified in this manner, from the total T
      cell counts, we found that the residual normal T-cell compartments were small (0
      to 0.155 x 10(9)/L) in four of the six patients. Sezary cell counts by peripheral
      blood smear analysis by routine light microscopy underestimated the number of
      malignant T cells. Markedly elevated CD4/CD8 ratios (10 to 90) occurred in all
      cases, reflecting expansion of the CD4+ malignant population and parallel
      reduction of the normal residual CD8+ subset. CONCLUSIONS: Patients with
      erythrodermic cutaneous T-cell lymphoma often have markedly depressed levels of
      normal blood T cells, to the range seen in advanced acquired immunodeficiency
      syndrome, and absolute numbers of malignant cells substantially exceed those
      recognized with less sensitive techniques.

PMID- 8304759
TI  - Bowen's disease of the nail bed and periungual area. A clinicopathologic analysis
      of seven cases.
AB  - BACKGROUND: This article describes the clinical and histologic features of seven
      cases of Bowen's disease (BD) of the nail bed, evaluates the role of human
      papillomavirus in the bowenoid change, and discusses optimal therapy.
      OBSERVATION: The patients presented with the clinical features of verruca
      vulgaris (n = 3), nail dystrophy and onycholysis (n = 2), paronychia (n = 1), and
      acral melanoma (n = 1). Histologically, the lesions demonstrated acanthosis,
      hyperkeratosis, and anaplasia, involving the full thickness of the epithelium. In
      four cases, human papillomavirus type 16 was demonstrated by in situ
      hybridization. Six lesions were treated by Mohs micrographic surgery, and one
      case was treated with topical 5% fluorouracil. In two cases, lesions recurred 1
      and 2 years following surgery. In the case treated with topical 5% fluorouracil,
      residual BD was found 6 weeks after therapy. This case was then treated by Mohs
      surgery. CONCLUSIONS: Bowen's disease of the nail bed and periungual area may
      present clinically as various inflammatory and neoplastic conditions. An
      important clinical finding in differentiating BD of the nail bed from verruca is
      the presence of scaling and onycholysis that are out of proportion to the
      verrucous changes. Human papillomavirus type 16 may be etiologically related to
      BD of the nail bed and periungual area. Mohs micrographic surgery is recommended
      for adequate excision and maximal preservation of normal tissue and function.

PMID- 8304760
TI  - Transcriptional control and cell type specificity of HPV gene expression.
AB  - BACKGROUND: Papillomaviruses are of great medical interest as they are causally
      associated with benign and malignant neoplasia of mucosal and cutaneous
      epithelia. The viral genome can be viewed as a control unit that releases signals
      in form of transforming proteins in infected epithelial cells. These proteins
      create a molecular environment favorable for papillomavirus biology and an
      expanded cell population for multiplication of the virus. On the other side, the
      genome receives signals through cellular transcription factors. OBSERVATIONS:
      Cellular transcription factors help the virus to identify the epithelial target
      cell, and they provide information about mitotic and physiologic signals to the
      epithelium and its differentiation state. Present research concentrates on the
      question how these distinct functions are brought about by factors that are
      ubiquitous rather than cell-type specific, such as NFI/CTF, TEF-1, AP-1, oct-1,
      and the progesterone receptor. Papillomaviruses have the additional capability to
      generate positive and negative feedback loops of gene expression through the
      virally encoded E2 proteins, a necessary tool to achieve long-term persistence.
      CONCLUSIONS: An intricate interplay between cellular and viral transcription
      factors is a prerequisite for epithelial specificity, physiologic responses, and
      persistence of papillomavirus infections.

PMID- 8304761
TI  - The genetics of psoriasis.
AB  - BACKGROUND AND DESIGN: Psoriasis is a member of a class of common, HLA-associated
      conditions in which disease susceptibility appears to be heritable. However, the
      mode of inheritance of these diseases has been difficult to define in simple
      mendelian terms. Psoriasis displays one of the strongest HLA associations of this
      class of diseases. However, only a small fraction of those who carry the
      implicated HLA susceptibility alleles develop disease, and it has proven
      difficult to demonstrate that the HLA associations observed are due to formal
      genetic linkage between the disease and the HLA locus. Although the role of
      environmental factors in psoriasis and these other diseases cannot be denied, the
      participation of additional genes, not necessarily linked to HLA, has long been
      suspected. OBSERVATIONS: Epidemiologic and immunogenetic data are reviewed and
      analyzed, which demonstrate that a predisposition to psoriasis is heritable, and
      which implicate genes of the HLA locus as necessary but not sufficient
      determinants of psoriasis. Recent developments in human genome research are
      described, which make possible a systematic search for additional genetic
      determinants of psoriasis, including those unlinked to HLA. CONCLUSIONS: As one
      of the most common, most heritable, and most highly HLA-associated examples of
      this class of HLA-associated diseases, psoriasis represents an ideal target for
      the application of this emerging genomic technology.

PMID- 8304762
TI  - Abnormalities of p53 protein expression in cutaneous disorders.
AB  - Abnormalities in the p53 gene and in expression of its protein product are among
      the most frequent changes demonstrated in a variety of human cancers. p53 Is a
      nuclear phosphoprotein that in the natural form or "wild-type" can bind to DNA
      and prevent cells from entering into the S phase of the cell cycle. There is an
      increase in wild-type p53 after exposure of the skin to UV light, which allows
      for DNA repair before replication that would make DNA damage permanent. A loss of
      this protective influence destabilizes the genome. Mutation of the p53 gene
      commonly causes a defective protein that is degraded more slowly and accumulates
      in the cell to the extent that it becomes detectable by routine
      immunocytochemistry. These abnormalities precede the development of cancer in
      some examples. Studies of precursor lesions have used mainly immunohistochemical
      techniques that show p53 protein overexpression. The relationship between such
      overexpression and actual mutation of the p53 gene is controversial because
      overexpression of "wild-type" p53 protein also can occur. Mutations in the p53
      gene have been observed in many actinic keratoses, basal cell carcinomas, and
      squamous cell carcinomas, and in a small proportion of malignant melanomas.
      Specific types of pyrimidine transitions have pointed to a role for UV light in
      these mutations. Molecular analysis is needed to determine whether or not
      immunocytochemical staining is truly reflective of mutation or is due to some
      other mechanism that causes an increased expression of wild-type p53.

PMID- 8304763
TI  - Corridor dermatology consultation en passant.

PMID- 8304764
TI  - Significance of human papillomavirus-induced squamous cell carcinoma to
      dermatologists.

PMID- 8304765
TI  - Subcutaneous nodule on the lower leg. Primary neuritic leprosy with nerve
      abscess.

PMID- 8304766
TI  - Ulcerative lesions in a gardener. Cutaneous nocardiosis.

PMID- 8304767
TI  - Cutaneous erythematous nodular lesion in a crab fisherman. Protothecosis.

PMID- 8304768
TI  - Diffuse petechial pustular lesions in a newborn. Disseminated Listeria
      monocytogenes.

PMID- 8304769
TI  - Telogen effluvium.

PMID- 8304770
TI  - Other questions on basaloid follicular hamartoma.

PMID- 8304771
TI  - Fibrillary protein deposits with tubular substructure in a systemic disease
      beginning as cutis laxa.

PMID- 8304772
TI  - The effect of ibuprofen on serum dapsone levels and disease activity in
      dermatitis herpetiformis.

PMID- 8304773
TI  - Cutaneous toxicity of ibuprofen.

PMID- 8304774
TI  - Debilitating edema associated with itraconazole therapy.

PMID- 8304775
TI  - Lomefloxacin photosensitivity.

PMID- 8304776
TI  - Tongue necrosis secondary to ergotamine tartrate in a patient with temporal
      arteritis.

PMID- 8304777
TI  - Lymphocyte infiltration of the skin in transgenic mice carrying the human
      interleukin-2 gene.
AB  - Inflammatory lesions of the skin such as erythema, depigmentation and hair loss
      were observed in C57/BL6(B6) transgenic mice that carried an intact human genomic
      interleukin-2 gene (gIL-2 transgenic mice). Accumulation of T lymphocytes in the
      perivascular and periadnexal areas of the dermis was the first change, followed
      by dermal papillary oedema, which occurred before the development of macroscopic
      skin lesions. In 3- or 4-week-old transgenic mice with slight erythema and
      depigmentation of the skin, there was an increase in the number of perivascular
      lymphocytes accompanied by the diffuse infiltration of neutrophils and monocytes
      in the damaged skin. These morphological skin changes were not observed in non
      transgenic mice, which were bred together with transgenic litter mates. These
      findings suggest that lymphocyte infiltration of the perivascular space of the
      skin is a primary event of exogenously introduced human interleukin-2 gene,
      resulting in secondary cutaneous changes in gIL-2 transgenic mice.

PMID- 8304778
TI  - Growth and differentiation of normal human melanocytes in a TPA-free, cholera
      toxin-free, low-serum medium and influence of keratinocytes.
AB  - Melanocyte cultures were obtained from a modification of the keratinocyte culture
      system MCDB153. Either promelanocytes or mature melanocytes were selected from
      epidermal cell primary cultures. Pure subcultures of actively dividing
      melanocytes of both types were grown in a low-serum medium totally deprived of
      TPA and cholera toxin called melanocyte growth medium (MGM). Early passaged cells
      from MGM primary cocultures were similar to normal adult human melanocytes in
      vivo, exhibiting numerous melanosomes, strong dopa positivity and a high
      dendricity. The ability of MGM to support melanocyte growth was mainly a
      consequence of its basic composition, combined with a low serum concentration.
      Bovine pituitary extract significantly enhanced melanocyte growth. Using complete
      MGM, in the absence of mitogens and keratinocytes, cell growth was maintained,
      but the differentiation of melanocytes decreased. The presence of keratinocytes
      was found to promote melanocyte growth. The coculture system used strongly
      suggests the action of soluble keratinocyte-derived factors. Keratinocyte contact
      was necessary to sustain melanocyte dendricity and melanization. Melanization and
      dendricity behaved mostly as independent features when keratinocyte influence was
      withheld. Our results underline the essential role of keratinocytes in the
      regulation of melanocyte growth and differentiation in a physiological culture
      system.

PMID- 8304779
TI  - Inositol phosphate formation and release of intracellular free calcium by
      bradykinin in HaCaT keratinocytes.
AB  - Phospholipase C-mediated release of inositol trisphosphate, followed by an
      increase in free intracellular calcium, is an important signal transduction
      pathway for several membrane receptors. In the present investigation, the
      coupling of various receptors to phospholipase C was studied in the human
      keratinocyte line HaCaT. Inositol trisphosphate formation was determined by anion
      exchange chromatography, and the release of intracellular calcium was analysed
      with the fluorescence probe Fura-2 AM. Activation of HaCaT keratinocytes with
      bradykinin resulted in a time- and dose-dependent release of inositol
      trisphosphate and intracellular calcium, with an EC50 value of 50 nM for
      bradykinin-induced inositol trisphosphate formation. The mediators and cytokines
      IL-1, IL-4, IL-6, IL-8, EGF and TGF alpha, as well as bombesin, prolactin,
      carbachol, substance P and retinoic acid, did not activate this pathway. The
      inability of the mediators examined to activate phospholipase C may be due to
      lack of the respective cognate receptors or to the use of other signal
      transduction pathways.

PMID- 8304780
TI  - Epithelioid cell melanomas have greater DNA ploidy abnormalities than spindle
      cell melanomas: cytological evidence for a higher malignant potential of the
      former.
AB  - The cellular DNA ploidy of 30 cases of malignant melanoma was measured by 4',6
      diamidino-2-phenylindole-DNA (DAPI-DNA) microfluorometry. DNA histograms and DNA
      index values were compared among melanomas of different cell morphology.
      Epithelioid cell melanomas often showed greater DNA aneuploidy than spindle cell
      melanomas in terms of histographic pattern. DNA index values of the former (mean
      +/- standard error, 1.84 +/- 0.31) were significantly higher than those of the
      latter (1.55 +/- 0.24; P < 0.05). The DNA index values of mixed-type melanomas
      were intermediate. These results indicate that the epithelioid cell melanomas
      have greater DNA ploidy abnormalities which are usually correlated with a greater
      malignant potential in pigmentary neoplasms. Thus our results confirm clinical
      evidence that melanoma patients with the epithelioid type of cells have a poorer
      prognosis than those with the spindle type of cells.

PMID- 8304781
TI  - Age- and sex-dependent change in stratum corneum sphingolipids.
AB  - We measured six stratum corneum sphingolipid species (ceramides 1-6) in 26 males
      and 27 females, and found a significant change in their percentage composition
      only among female subjects of different age groups. There was a significant
      increase in ceramide 1 and 2 with a corresponding decrease in ceramide 3 and 6
      from prepubertal age to adulthood. Thereafter the ratio of ceramide 2 to total
      sphingolipids decreased with age in contrast to ceramide 3 which showed an
      increase. Such a pattern of change in the aging population is different from that
      observed in scaly skin experimentally induced by tape stripping. The present
      results suggest a significant influence of female hormones on the composition of
      stratum corneum sphingolipids. Moreover, the different patterns of change in
      sphingolipid composition of stratum corneum lipids between scales from
      inflammatory skin and those from aged skin also suggest that epidermal
      biosynthesis of sphingolipids is influenced by epidermal proliferative activity.

PMID- 8304782
TI  - Isolation of cysteine proteinase inhibitor, cystatin A, from human nails.
AB  - A cysteine proteinase inhibitor was found in human nail extract treated with 0.01
      M Tris HCl buffer, pH 8.0. It had a 2-fold lower and a 4.5-fold higher activity
      than that of human skin and hair extracts, respectively. From 5.9 g of human
      nail, 0.1 mg of cysteine proteinase inhibitor was obtained. It was purified by
      sequential DE-52 ion exchange and carboxymethyl papain affinity chromatography.
      The purified inhibitor had an apparent molecular mass of 12 kDa as determined by
      sodium dodecyl sulphate polyacrylamide gel electrophoresis. It was more stable
      against heat and pH than most other proteins. Immunologically, it had the same
      antigenicity compared with human epidermal cystatin A. Its N-terminal amino acid
      sequence showed a mixed form comprising a full-length MIPG sequence a truncated
      IPGG sequence. This sequence was identical to human cystatin A consisting of 20%
      of the full-length and 80% of the truncated form. These results showed that human
      nail also contains cystatin A type cysteine proteinase inhibitor. Nails can be
      used as a source of cystatin A.

PMID- 8304783
TI  - Influence of phospholipid liposomes (PLL) on UVB-induced erythema formation.
AB  - Application of liposomal phospholipids (Natipide II) caused a significant
      decrease in erythema induced by UVB (280-312 mm) in patients with skin types II
      and III (n = 31). In accordance with findings in other organs, e.g. liver, the
      present findings suggest that phospholipids are capable of reducing H2O2
      formation and/or increasing glutathione synthesis in human skin, thus reducing
      erythema formation by preventing oxidative stress.

PMID- 8304784
TI  - Anti-inflammatory effects of eicosapentaenoic acid on experimental skin
      inflammation models.
AB  - Anti-inflammatory effects of eicosapentaenoic (EPA) and docosahexaenoic acids
      (DHA) were examined on three models of skin inflammation induced in mice by
      topical application of an arachidonic acid (AA) solution, ultraviolet-B (UVB)
      irradiation, and contact sensitization with dinitrofluorobenzene. Ear oedema
      reactions induced by AA and UVB irradiation were significantly suppressed in mice
      fed a daily dose of 300 mg/kg EPA for 2 weeks. The contact hypersensitivity
      reaction was not impaired by EPA. None of the skin reactions was significantly
      inhibited in mice fed DHA or safflower oil. The results suggest that EPA, but not
      DHA, has anti-inflammatory effects on AA- and UVB-induced acute inflammation
      reactions.

PMID- 8304786
TI  - Expression of smg p21A and ras p21 in epidermal neoplasms.

PMID- 8304785
TI  - gamma delta T-cell receptor-positive cells of human skin. II. Appearance in
      delayed-type hypersensitivity reaction.
AB  - In order to investigate the distribution and involvement of human gamma delta T
      cell receptor-positive (TCR+) cells in delayed-type hypersensitivity reactions of
      the skin, we examined the occurrence and kinetics of gamma delta TCR+ cells
      during skin reactions of allergic contact dermatitis. In normal human skin
      sections, gamma delta TCR+ cells were scarce. In allergic contact dermatitis from
      DNCB, increased gamma delta TCR+ cells were observed both in the epidermis and in
      the dermis from 48 h after the challenge. Most of the gamma delta TCR+ cells were
      TCR delta 1+ delta TCS1- BB3+ Ti gamma A+ (V delta 1- V delta 2+ V gamma 9+). The
      percentage of gamma delta TCR+ cells in the peripheral blood remained unchanged
      and a few gamma delta TCR+ cells in the skin lesions proliferated in situ. It is
      suggested that the gamma delta TCR+ cells in skin lesions of allergic contact
      dermatitis may not be involved in initiation of delayed-type hypersensitivity but
      may have some other roles responding to factors induced in the reaction.

PMID- 8304787
TI  - Epidermotropic neutrophilic granulocytes express MAC-1 (CD11b/CD18) rather than
      LFA-1 (CD11a/CD18).

PMID- 8304788
TI  - [Transrectal echography and prostate cancer. A personal view].

PMID- 8304789
TI  - [A double-blind study of the analgesic efficacy in kidney colic of the
      combination of dipyrone and spasmolytic with ketorolac trometamol].
AB  - We conducted a double-blind study in 34 patients to compare the analgesic
      efficacy in acute renal colic using 2.5 g dipyrone combined with a spasmolytic
      agent and 30 mg ketorolac tromethamine, diluted in 100 ml saline solution and
      injected intravenously. Clinical criteria and the observation of red cells in
      urine were used for the diagnosis. The intensity of the pain and its development
      were measured using visual analogue scales (VAS) and a scale of items showing
      patient improvement. The side effects were spontaneously mentioned by the
      patients and elicited by direct questioning. It can be confirmed with a beta
      error of 0.10 that the analgesic effect obtained by both treatments is similar.
      Nevertheless, the combination of dipyrone and spasmolytic produces more side
      effects, possibly due to the spasmolytic agent.

PMID- 8304790
TI  - [The urological complications of anticoagulant therapy].
AB  - Patients on anticoagulant therapy may develop urologic complications, the most
      common being hematuria. Other less common but more severe complications are
      spontaneous hemorrhage arising from urological structures, as spontaneous
      perirenal hematoma, or from extra-urological structures, such as the iliac psoas
      muscle or the anterior rectus abdominis muscle. We report on four patients on
      anticoagulant therapy for different reasons, with no previous history of trauma,
      who suddenly developed spontaneous bleeding with urologic consequences:
      spontaneous perirenal hematoma (2), hematoma of the iliac muscle (1) and the
      anterior rectus abdominis muscle (1). The diagnostic strategy, the usefulness of
      the different imaging techniques and our approach to these complications are
      discussed.

PMID- 8304791
TI  - [The usefulness of the carbohydrate antigen CA-50 in the prognosis of
      transitional-cell bladder carcinomas].
AB  - The carbohydrate antigen CA 50 is expressed in the epithelial tissue during the
      process of neoplastic transformation; i.e., transitional cell bladder carcinoma.
      The present study evaluated the biological behaviour of the CA 50 antigen in
      malignant superficial, deep localized and disseminated bladder tumors. One
      hundred subjects were entered into the study: 30 carefully selected healthy
      subjects comprised the first group and 70 patients with a diagnosed transitional
      cell bladder carcinoma comprised the second group. The serum CA 50 antigen was
      determined by immunofluorometric assay (Delfia CA 50 kit). Our results indicate
      that the carbohydrate CA 50 antigen can be utilized as a prognostic marker in
      patients with malignant bladder tumors. The serum antigen levels were higher for
      the more undifferentiated tumors and those in the advanced stages.

PMID- 8304792
TI  - [Urethral metastases of prostatic adenocarcinoma].
AB  - Although the penis is highly vascularized, secondary penile tumors are rare and
      28% of these metastasize from prostatic tumors. Urethral metastases are uncommon
      and may be caused by seeding following manipulation of the prostate with
      instruments or spread directly from the adjacent structures. This condition can
      be controlled and treated effectively with first or second line hormone therapy.
      Herein we describe a 65-year-old male with disseminated prostatic adenocarcinoma
      who presented multiple urethral metastases that were successfully treated with
      stramustine phosphate.

PMID- 8304794
TI  - [Kidney transplant with pediatric grafts from donors under a year old. The
      implantation technics].
AB  - Although the number of renal transplants performed in our country is high, it is
      far surpassed by the number of patients with end-stage chronic renal failure
      awaiting transplantation. The foregoing has led to the use of grafts from donors
      aged less than one year. Our series of 6 renal transplants in adults using grafts
      from these donors are presented. Both kidneys were transplanted in all cases, but
      two different techniques were utilized. The kidneys were transplanted "en bloc"
      in 4 cases and sequentially into the right iliac fossa in 2 cases. In 2 of the
      cases submitted to "en bloc" transplantation, the grafts never functioned and
      were lost due to venous thrombosis. The remaining cases (2 "en bloc" and 2
      sequential) are functioning well at 6 to 20 months follow-up, with no vascular or
      urinary complication. In our view, the kidneys from pediatric donors less than
      one year old are an acceptable alternative for transplantation into adult
      patients using the classical "en bloc" or the sequential technique, although in
      certain aspects the latter may offer more advantages over the former.

PMID- 8304793
TI  - [The therapeutic management of the rupture of a kidney graft].
AB  - From a consecutive series of 106 renal transplants, we present our experience on
      spontaneous renal allograft rupture. This complication appeared in 6 patients,
      which accounts for 5.6% of the overall group: four patients (66.6%) had acute
      rejection, two (33.3%) developed thrombosis of the renal vein (one of which
      coincided with rejection), and rupture was attributed to trauma in one patient
      (16.6%). Rupture was diagnosed within the first two weeks after transplant in
      five patients and on day 27 in one patient. The therapeutic approach was
      determined according to the cause of the rupture. In our view, nephrectomy is
      warranted in those cases with venous thrombosis and in acute rejection correction
      of hypovolemia and adequate immunosuppression are essential. Drainage of
      perirenal hematoma is the first step when conservative surgical treatment is
      required. We use three-dimensional renal corsetage with polyglycolic acid mesh
      (PAM) for hemostasis and to prevent expansion and fragmentation of the
      parenchyma. PAM is easy to handle and covers the kidney completely and uniformly.
      Two nephrectomies were carried out and in both cases thrombosis of the renal vein
      was diagnosed. PAM was placed in two cases: one with rejection and the other with
      trauma. The remaining two patients were managed conservatively due to the good
      response of rejection to immunosuppressor therapy and the patients response to
      medical treatment. There were no deaths and complications were observed in only
      one patient (16.6%). All patients with preserved transplant (66.6%) had a good
      course and renal function was preserved.

PMID- 8304795
TI  - [The ovarian vein syndrome. Its treatment by percutaneous embolization and a
      review of the same].
AB  - Since Clark first described the ovarian vein syndrome in 1964, there has been
      much controversy over its existence. We report two cases of ovarian vein syndrome
      whose presenting feature was lumbar pain. Following treatment by percutaneous
      coil embolization of the corresponding ovarian vein, the symptoms rapidly
      improved and the patients are asymptomatic at 8 and 21 months follow up. We
      underscore the importance of symptomatic relief over the radiologic findings. The
      most important aspects and controversies of this syndrome are briefly reviewed.

PMID- 8304796
TI  - [An arteriovenous fistula as a complication of percutaneous nephrostomy].
AB  - Percutaneous nephrostomy has emerged as a substitute for surgical nephrostomy.
      The complication rate is low, hematuria being one of the most common. Treatment
      should be conservative while possible since the clot plays an important role in
      the tamponade of hemorrhage. Arteriovenous fistulas following percutaneous
      nephrostomy are rare. Diagnosis is by arteriography and treatment is by selective
      embolization.

PMID- 8304797
TI  - [Pregnancy via spermatozoa aspirated from the ductus deferens and fertilization
      in vitro].
AB  - The possibility of aspirating sperm from the first segments of the seminal tract
      by microsurgical techniques has permitted in vitro fertilization of the oocytes
      of the partners of men with obstructive azoospermia and ejaculation disorders.
      Sperm can be aspirated from the epididymis by microsurgical techniques in those
      cases with deferent duct agenesis or other obstructive pathologies, or from the
      deferent duct if spermatogenesis is unimpaired and there is no epididymal
      obstruction, but spermatozoa do not reach the ejaculate. We previously reported a
      pregnancy achieved by in vitro fertilization using sperm aspirated from the
      epididymis and the present article reports the first pregnancy achieved in our
      country using sperm aspirated from the deferent duct of the spouse with aspermia
      of psychogenic origin. A micropipette was utilized to obtain the sample, which
      was prepared using the mini-Percoll method. A total of 10 million motile
      spermatozoa were obtained and 6 of the 15 oocytes aspirated from the spouse were
      fertilized. The 3 embryos transferred to the fallopian tube resulted in a twin
      pregnancy that was carried to term.

PMID- 8304798
TI  - [Urethral duplication: apropos a case].
AB  - We report a case of dorsal blind-ending urethral duplicity in a 37-year-old male
      who presented dysuria and occasional mucopurulent discharge. The presumptive
      diagnosis was made on the findings at physical examination and was corroborated
      by retrograde urethrography. The patient was treated conservatively because the
      symptoms were minimal.

PMID- 8304799
TI  - [Fraley's syndrome: a case report].
AB  - A case of Fraley's syndrome is described. Intermittent nephralgia was the
      presenting symptom. The diagnosis was made on the radiologic finding of
      obstruction of the infundibulum arising from vascular compression. The diagnostic
      and therapeutic aspects of this uncommon cause of obstruction of the infundibulum
      are discussed.

PMID- 8304800
TI  - [Testicular malacoplakia].
AB  - A rare case of testicular malacoplakia is described herein. To our knowledge only
      32 cases have been reported up to 1989. The microscopic features are described
      and the literature is briefly reviewed.

PMID- 8304801
TI  - [Right hematocolpos and hematometra with left renal agenesis. A rare association.
      Apropos a case].
AB  - Although this anomaly is seen more frequently, the present case is unique in that
      the genital anomaly (imperforate vagina with the subsequent hematocolpos and
      hematometra) was associated with contralateral renal agenesis, whereas the cases
      reported in the literature have all been ipsilateral. Like most of the cases, the
      presenting symptom was acute urinary retention arising from extrinsic compression
      of the genital mass on the lower urinary tract. The embryological aspects of the
      genitourinary system concerning the present case are discussed, as well as some
      of the hypotheses that have been put forward to explain the etiology of these
      anomalies, although these have been developed on the basis of the associated
      ipsilateral anomalies observed.

PMID- 8304802
TI  - [Double tumor pathology: simultaneous renal oncocytoma and colonic carcinoma].
AB  - We report a case of renal oncocytoma associated with adenocarcinoma of the colon.
      Although the preoperative evaluation had disclosed a mass in the superior pole of
      the left kidney, renal oncocytoma had not been suspected and the foregoing was
      diagnosed pathologically from the intraoperative biopsy. The association of renal
      oncocytoma and other extraurological tumors reported in the literature are
      reviewed and the diagnostic and therapeutic aspects are discussed.

PMID- 8304803
TI  - [Symptomatic renal leiomyoma].
AB  - Symptomatic leiomyoma of the kidney is an uncommon, large, solitary, benign
      mesenchymatous tumor that must be distinguished from renal cell carcinoma.
      However, the diagnostic imaging techniques currently available do not permit
      determining the benign nature of the lesion with precision and radical excision
      of the compromised kidney is warranted, as in the case described herein.

PMID- 8304804
TI  - Common iliac artery-ureteral fistula: a case report and literature review.
AB  - The iliac artery-ureteral fistula is a rare complication that can produce a
      catastrophic situation or even death. Diagnosis is difficult to make
      preoperatively unless it is highly suspected. We report an additional case that
      was successfully resolved by surgery and review the previously published cases.

PMID- 8304805
TI  - [Antioxidative treatment in myocardial reperfusion ischemia].
AB  - Perfusion-induced myocardial ischaemia is observed in several situations: chronic
      coronary insufficiency, unstable angina, myocardial infarction, and during
      coronary angioplasty or bypass surgery. Oxygen-derived free radicals are
      liberated in large quantities during myocardial reperfusion ischaemia. Though
      very toxic in experimental studies, the responsibility of these free radicals in
      myocardial injury remains to be demonstrated clinically. Oxidant stress,
      characterised by an imbalance between the free radical attack and insufficient
      cellular defense seems partially responsible for reperfusion arrhythmias and post
      ischemic stunning. On the other hand, its role is less evident in prolonged
      myocardial ischaemia causing irreversible myocardial lesions such as infarction.
      Antioxidant therapy is under evaluation in clinical trials. There are several
      options: some prevent the formation of free radicals by inhibiting the
      biochemical reactions which may produce them or by limiting the intervention of
      the neutrophils--the "fulcrum" of free radicals formations. Other antioxidant
      therapies inactivate free radicals as they are formed by promoting their
      degradation or their neutralisation. Experimental data is profuse and discordant.
      The models are very different. The first clinical trials are under way using
      either specific antioxidant molecules or molecules having other beneficial
      effects: in the latter case, the benefit of the antioxidant action is more
      difficult to demonstrate. Antioxidant therapy could play a role in surgical
      myocardial protection, especially of transplant organs, in very early forms of
      ischaemia. It could also prevent the pejorative hemodynamic consequences of
      myocardial stunning of the border zones of infarction, so enabling patients to
      survive a difficult period. The results of on-going studies should clarify the
      role of antioxidant therapy in reperfusion-induced myocardial ischaemia.

PMID- 8304806
TI  - [From ischemia to reperfusion lesions].
AB  - It is well established that early reperfusion of ischemic myocardium limits or
      even prevents necrosis. However, sometimes restitution of coronary flow to the
      ischemic myocardium may precipitate a sequence of events that would have occurred
      either later or not at all. To prove the existence of reperfusion-induced injury,
      it is necessary to show that cells, potentially viable before reperfusion, are
      killed by the onset of reperfusion. The consequences of reperfusion are
      reperfusion-induced arrhythmias, myocardial stunning, accelerated necrosis and
      lethal reperfusion injury. The two main theories explaining the development of
      reperfusion injury are formation of free radicals and cellular calcium overload.
      Free radicals produced during early reperfusion may cause oxidant stress to
      membrane lipids and proteins associated with a potassium loss and a temporary
      cytosolic calcium overload. Results of experiments with free radical scavengers
      are contradictory for unknown reasons suggesting that reperfusion injury is a
      complex event innowing endothelial damage, leukocyte-plugged vessels,
      microvascular damage and production of heat-shock proteins.

PMID- 8304807
TI  - [Methods of quantitative electrocardiology proposed to evaluate the extent of
      ischemia and necrosis during the acute phase of myocardial infarction].
AB  - Many clinical reports have been published over the last decade concerning new
      quantitative methods of electrocardiography designed to assess infarct size, to
      monitor the severity of ischaemia, especially during thrombolysis or coronary
      angioplasty, and to analyse prognostic factors. Although very different, these
      methods give concordant results. They have become so reliable that they play an
      important role in the management of acute myocardial infarction.

PMID- 8304808
TI  - Cumulative enzyme release as a measure of infarct size in patients with acute
      myocardial infarction receiving thrombolytic therapy.
AB  - Infarct size can be assessed in patients with myocardial infarction by
      calculating cumulative enzyme release. The two compartment model is used in
      patients who received thrombolytic therapy as well as in patients who were not
      treated with thrombolytic agents. The most practical approach is to calculate
      cumulative release of lactate dehydrogenase (LDH). Blood samples have to be
      obtained twice daily during the first two days, and once daily during day three
      to five. Cumulative LDH release can then be calculated with help of a simple
      computer program, presently available for use on a PC. Cumulative enzyme release
      was calculated from the patients who were included in the study with
      intracoronary streptokinase conducted by the Intervuniversity Cardiology
      Institute of the Netherlands, in the trial conducted by Anderson, in the ISAM
      study, and in the trial with rt-PA versus placebo that was coordinated by the
      European rt-PA study group. In all studies it was demonstrated that thrombolytic
      therapy led to a limitation of infarct size (less cumulative enzyme release) when
      compared to controls. In future trials calculation of cumulative enzyme release
      will have to be incorporated in the design of those trials in which the
      effectiveness of proposed new therapeutic regimens (like acute PTCA) is tested in
      patients with acute myocardial infarction and will be compared to the nowadays
      "standard" therapy with thrombolytic agents.

PMID- 8304810
TI  - [Angiography of the left ventricle].
AB  - Left ventricular angiography in the 30 degree right anterior oblique projection
      is the reference method of calculating volumes and assessing segmental wall
      motion. The calculation of volumes is based on the surface-length or Simpson's
      methods which assume that the ventricle has an ellipsoid shape. The use of both
      the right and left anterior oblique projections only slightly improves the
      accuracy of the method and is not necessary in routine procedures. The global
      parameters of left ventricular function are the end-systolic and end-diastolic
      volumes and the ejection fraction. Segmental wall motion assessment provides a
      more precise analysis of left ventricular function. Many methods have been
      described but only two have been validated clinically: the Stanford method
      proposed by Ingels in which fractional shortening is calculated with respect to a
      point situated at 69% of the length of the axis between the apex and the anterior
      aortic border, and the more complex Rotterdam method reported by Slager. The
      introduction of digitisation of the image has enabled calculation of these
      different parameters in routine investigations.

PMID- 8304809
TI  - [Myosin: a necrosis marker: update and trends].
AB  - Plasma myosin heavy chain fragments are a "quantitative indicator of myocardial
      necrosis" in patients with myocardial infarction. Myosin assay enables:
      retrospective diagnosis of necrosis; assessment of infarct size; evaluation of
      the scarring process and risk of recurrence; analysis of methods of cardioplegia
      in cardiac surgery by detection of perioperative infarction; determination of the
      long-term prognosis of post-infarct patients.

PMID- 8304811
TI  - [Angioscintigraphy in the development of left ventricular dysfunction and
      prognosis of ischemic heart diseases].
AB  - Radionuclide angiography at rest or on effort is one of the most valuable
      diagnostic and prognostic non-invasive methods for investigating left ventricular
      function. This procedure provides perfectly reproducible quantitative
      information; However, its usefulness in detecting myocardial ischaemia is
      debatable: on the other hand, its prognostic value is uncontested and its role in
      therapeutic assessment, especially in myocardial infarction, is growing.

PMID- 8304812
TI  - [How to assess dysfunction of the left ventricle after myocardial infarction with
      Doppler echocardiography].
AB  - Doppler echocardiography is one of the most useful non-invasive methods of
      cardiac imaging in patients who have suffered myocardial infarction because it
      provides important information such as the immediate identification of the
      infarct, its size, possible mechanical complications and an assessment of its
      effects on global ventricular function, all in a single procedure. Several
      mathematical formulae have been proposed to quantify global left ventricular
      function from two-dimensional imaging; the most commonly used are the surface
      length method based on the parasternal short axis view (V = 5/6 A.L) and
      reconstruction by Simpson's method based on two orthogonal apical views.
      Hemodynamic data may be obtained by Doppler studies, especially of the ejection
      phase (transaortic velocities and cardiac output determination) and left
      ventricular filling. The effects of left ventricular dysfunction on the right
      heart may be evaluated when tricuspid regurgitation is present as right
      ventricular and pulmonary artery systolic pressures can be determined. The non
      invasive nature of Doppler echocardiography enables documentation of these
      parameters of ventricular function as often as the patient's clinical status
      requires during follow-up, or to assess the effects of treatment in the post
      infarction period.

PMID- 8304813
TI  - [Evaluation of prognosis and myocardial ischemia using thallium in myocardial
      tomoscintigraphy].
AB  - Thallium scintigraphy holds a unique position amongst the methods available for
      evaluating the prognosis of coronary patients: it enables quantification of
      underperfused myocardium and evaluates already constituted ventricular damage
      (irreversible necrosis) and areas at risk of future coronary events (viable but
      ischemic myocardium). In a series of 1,926 patients who underwent exercise stress
      or dipyridamole Thallium myocardial scintigraphy for angina pectoris and followed
      up fort an average of 34 months, the following features were observed: the long
      term prognosis in patients with normal myocardial scintigraphy (715 patients) was
      identical to that of a normal population of the same age (0.11% cardiovascular
      deaths per year) whereas the cardiovascular mortality was 15 times higher in
      cases with a pathological scintigraphy: finally, the long-term prognosis
      (cardiovascular deaths, infarcts or secondary revascularisation) was directly
      related to the severity of the initial lack of Thallium uptake. This method was
      used to assess the prognosis and evaluate the myocardial ischaemia in 75 patients
      who underwent complete surgical revascularisation fort ischaemia, 50 of whom had
      previous myocardial infarction: all patients had at least one arterial bypass
      graft: 39% of the myocardium was underperfused before revascularisation; this
      procedure reduced by 80% (p < 0.0001) the zones of reversible underperfusion but
      also zones of irreversible underperfusion by 17% (p = 0.04). The results were
      particularly impressive in patients who underwent revascularisation with an
      arterial pedicle (left and right internal mammary, gastroepiploic alone or in
      association) as 91% of the ischemic territories recovered on average 13 days
      after revascularisation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8304814
TI  - [Mediators of the vascular endothelium as markers of myocardial ischemia and
      reperfusion].
AB  - Myocardial ischaemia may occur during spasm or thrombosis of the coronary
      arteries. The vascular endothelium plays an essential role in the lesions
      observed during ischaemia and myocardial reperfusion by the intermediary of the
      numerous endothelium-derived vasoactive factors. These include the "endothelium
      derived relaxing factors" (EDRFs) nitrous oxide, prostacyclin, which are
      vasodilators and platelet antiaggregants ant the "endothelium-derived contracting
      factors" (EDCFs), endothelin, PGH2, oxygen-free radicals which are
      vasoconstrictive. The endothelial cells also produce the platelet activating
      factor and factors essential for coagulation. The metabolism and biological
      properties of these different mediators are reviewed. During the phenomena of
      myocardial ischemia-reperfusion, endothelial regulation is activated by tissue
      hypoxia and reduction of coronary flow and perfusion pressure. This regulation
      also depends on the functional state of the arteries (macroscopically normal or
      pathological). These vasomotor phenomena are associated with the effects of
      platelet aggregation and myocardial accumulation of neutrophil polynuclear blood
      cells. During the second phase of reperfusion cellular lesions are produced by
      the generation of cytotoxic oxygen-free radicals. Assays of mediators present a
      clinical interest when the modalities of sampling have been fixed (systemic blood
      samples or during cardiac catheterisation, sites of sampling, choice of timing of
      sampling with respect to the biological half lives of the mediators). Determining
      a correlation between the in vitro biological effects on those in isolated organs
      and clinical data has become possible with the improvement in techniques of
      sampling and the increasing collaboration between biologists and clinicians.

PMID- 8304815
TI  - [Identification and evaluation of free radicals in the sequence cardiac ischemia
      reperfusion].
AB  - The role of free radicals (FR) has been suggested in the development of ischaemia
      induced myocardial reperfusion. When the equilibrium between the cellular sources
      and defense system is disturbed, FR may react with cellular components and
      produce a number of lesions. In general, the action of FR is shown indirectly by
      studying the effects of substances interfering with the production or the
      elimination of FR or of systems which produce FR on the physiopathological
      consequences of ischaemia and reperfusion. A physico-chemical technique,
      Electronic Paramagnetic Resonance (EPR) has been used in biology. The high
      reactivity and the very short life span of several types of FR pose
      methodological problems. A "stabilisation" of FR may be obtained by spin
      trapping, a technique which consists of adding a diamagnetic substance to the
      reaction which forms covalent bonds with FR and forms a stable, detectable
      radical product. This technique has enabled identification and evaluation of FR
      liberated in the perfusion fluid of isolated perfused rat hearts and to determine
      the importance of the different mechanisms of production.

PMID- 8304816
TI  - [Reperfusion arrhythmia].
AB  - Reperfusion arrhythmias were described from the first trials of intracoronary
      thrombolysis for myocardial infarction. The prevalence of ventricular
      fibrillation during intravenous thrombolysis is low (< 7%) and comparable to that
      observed with classical treatment. Holter recording shows that ventricular
      tachycardia and accelerated idioventricular rhythms occur in over 80% of cases.
      These arrhythmias are generally well tolerated and do not require specific
      therapy. A bradycardia-hypotension syndrome is observed in about a quarter of
      reperfused patients, nearly always in inferior wall infarction. It normally
      resolves spontaneously or after atropine or vascular filling. Reperfusion is
      associated with a clearcut increase in the number of episodes of arrhythmia. Some
      arrhythmias such as sustained ventricular tachycardia, early accelerated
      idioventricular rhythms (occurring in the first 6 hours) or the bradycardia
      hypotension syndrome may be considered as non-invasive criteria of reperfusion.
      More severe ischemia and sudden reperfusion favour the arrhythmogenicity of
      reperfusion in the animal. Recent data suggest that this may be the case in the
      clinical context. In some uncontrolled studies, lidocaine, betablockers and
      aspirin did not affect the prevalence of the arrhythmias. Preliminary trials
      indicate that flunarizine and captopril may reduce the incidence of reperfusion
      arrhythmias in man. Ventricular arrhythmias and myocardial stunning could be the
      result of sa single phenomenon (the extent of the ischemic lesions or reperfusion
      lesions). Studies currently under way should clarify the relationship between the
      incidence of arrhythmias, the severity of stunning and myocardial recovery.
      Protocols evaluating therapeutic interventions on the reperfusate should include
      Holter monitoring.

PMID- 8304817
TI  - [Evolution of the ST segment in myocardial reperfusion].
AB  - Intracoronary thrombolysis showed the chronological order of clinical electric
      and biological changes following the reestablishment of coronary flow. These
      changes make up the reperfusion syndrome; ST segment changes are part of this
      syndrome. They occur in practically all cases at the moment of reperfusion. The
      ST elevation may regress more or less rapidly or, on the contrary, increase
      transiently to a greater or lesser degree. When associated with other criteria of
      reperfusion-enzyme changes, arrhythmias, ST changes contribute to the indirect
      diagnosis of reestablishment of coronary flow. Rapid decrease in ST segment
      elevation is usually associated with a good myocardial outcome. The prognostic
      significance of transient increases in ST elevation--so called "reperfusion
      ischaemia"--is not fully understood, in particular its relationship to myocardial
      reperfusion injury. The myocardial prognosis after reperfusion may be the
      "biological" sum of cellular lesions due to ischaemia and reperfusion.

PMID- 8304818
TI  - [Calcium channel antagonists and myocardial ischemia or ischemia/reperfusion].
AB  - Many theoretical and experimental studies suggest that calcium antagonists drugs
      should be useful in pathological situations of myocardial ischemia or
      ischemia/reperfusion. This therapeutic model was tested in controlled trials of
      angina, post-infarction and cardiac surgery. The authors undertook a meta
      analysis of these trials using the occurrence of myocardial infarction or death
      as criteria of judgement. No long-term benefits seem to be associated with the
      dihydropyridines such as nifedipine and nicardipine in anginal patients. In
      unstable angina, betablockers seem to be more effective but the difference is not
      statistically significant. In the post-infarction period, nifedipine does not
      reduce the risk of recurrence of myocardial infarction and may even increase the
      mortality by 15%, though this was not significant in the 9,055 patients studied
      (p = 0.08). Verapamil and diltiazem globally reduce the risk of recurrent
      infarction by 21% (p = 0.009) but not mortality (p = 0.52). Because of the small
      numbers of patients and the low prevalence of observed events, no useful
      conclusions can be drawn from studies of calcium antagonists in cardiac surgery.
      The results of the validation of the therapeutic model "calcium antagonists in
      pathological situation of myocardial ischemia or ischemia/reperfusion" does not
      justify the labels "anti-ischemics" or "cardio protectors" often applied to the
      calcium antagonists.

PMID- 8304819
TI  - [Action of converting enzyme inhibitors on myocardial ischemia and reperfusion
      injuries].
AB  - During myocardial ischaemia, either in chronic coronary insufficiency or the
      acute phase of myocardial infarction, the renin-angiotensin system is activated
      which, by its deleterious cardiac effects, aggravates the ischaemia. Angiotensin
      Converting Enzyme (ACE) inhibitors, by their indirect effects (improved
      conditions of left ventricular load, negative inotropism, attenuation of
      catecholaminergic stimulation), reduce myocardial oxygen consumption, and by
      their direct coronary vasodilator effect reduce myocardial ischaemia. In
      addition, by attenuating the formation of oxygen-free radicals, by participating
      in the inactivation of some of them and protecting the lysosomal membranes, they
      combat reperfusion injury. In the animal model of acute myocardial infarction,
      they reduce myocardial infarct size and the prevalence of reperfusion
      arrhythmias. In the clinical situation, their effects on the ischemic response to
      effort in anginal patients remain controversial, appear to be more marked in
      abnormalities of the coronary micro-circulation especially in syndrome X and in
      hypertensive heart disease. In ischemic heart disease, long-term treatment may be
      beneficial by their trophic coronary and myocardial effects and two large scale
      trials report a decrease in the recurrence of myocardial infarction with ACE
      inhibitors. In the acute phase of myocardial infarction if their possible actions
      on reducing the infarct size and reperfusion arrhythmias require further
      confirmation, they do limit expansion of the infarct and decrease early left
      ventricular dilatation. However, the appreciation of tolerance is variable and
      the timing of their introduction remains controversial.

PMID- 8304821
TI  - Buffer-stimulated citrate efflux in Penicillium simplicissimum: an alternative
      charge balancing ion flow in case of reduced proton backflow?
AB  - Organic acids excreted by filamentous fungi may be used to win metals from
      industrial secondary raw materials. For a future commercial use a high production
      rate of organic acids is necessary. The conditions under which the commercially
      used fungus Aspergillus niger excretes high amounts of citric acid can not be
      maintained in metal leaching processes. However, Penicillium simplicissimum
      showed an enhanced citric acid efflux in the presence of an industrial filter
      dust containing 50% zinc oxide. Because Good buffers of high molarity were able
      to mimic the effect of zinc oxide, the high buffering capacity of zinc oxide and
      not an effect of the zinc ions was held responsible for the enhanced citric acid
      efflux. The presence of ammonium and trace elements reduced this buffer
      stimulated citric acid efflux, whereas the plant hormone auxine canceled this
      reduction. This citric acid efflux was influenced by a depolarization of the
      membrane: the freely permeable compound tetraphenylphosphoniumbromide decreased
      the citric acid efflux, without decreasing intracellular citric acid or
      consumption of glucose and oxygen. Vanadate, an inhibitor of the plasma membrane
      H(+)-ATPase also reduced the buffer-stimulated citric acid efllux. The role of
      the efflux of citrate anions as an alternative charge balancing ion flow in case
      of impaired backflow of extruded protons because of a high extracellular
      buffering capacity is discussed.

PMID- 8304822
TI  - Biochemical studies on the lethal effects of solar and artificial ultraviolet
      radiation on Staphylococcus aureus.
AB  - The effects of UV-B radiation generated in the laboratory and as a component of
      sunlight on the viability and particular biochemical activities of the bacterium
      Staphylococcus aureus have been examined. UV-B radiation progressively inhibits
      protein synthesis (assayed as 3H-alanine incorporation) and kills cells. Cell
      respiration, and RNA and DNA synthesis (3H-uridine and 3H-thymidine
      incorporation) were not greatly affected by UV-B irradiation. The OH. and 1O2
      free radical scavengers protected cells against killing and inhibition of protein
      synthesis by UV-B, suggesting that such radicals mediate the effects of UV-B on
      this organism. A similar protective effect using a ferric ion chelator suggests
      an important role for metallic ions in UV-B lethality.

PMID- 8304823
TI  - Ambulatory surgery. A more cost-effective treatment strategy?

PMID- 8304820
TI  - Molecular biology of membrane-bound H2 uptake hydrogenases.

PMID- 8304824
TI  - Postoperative pain management.
AB  - OBJECTIVES: To examine the relationship between analgesia and clinical outcome
      and to review new methods of delivering opioid analgesics and new pharmacologic
      analgesic agents. DATA SOURCES: A computer-assisted search of the literature on
      postoperative pain management, and a review of those areas in which new
      approaches have led to a change in clinical practice. RESULTS: Current research
      focuses on the ability of analgesia to decrease perioperative complications.
      Recent advances allow enhanced postoperative analgesia with a low incidence of
      side effects. Administration of opioids via a patient-controlled device or via an
      epidural catheter yields excellent analgesia with a low rate of side effects
      compared with intramuscular opioids. Several non-narcotic, parenteral drugs,
      including ketorolac tromethamine and alpha 2-adrenergic agonists are now
      available. These drugs decrease opioid requirement, and thus the rate of serious
      side effects, including respiratory depression. Moreover, because these drugs act
      at sites other than opioid receptors, they may enhance the quality of analgesia
      at the same time they decrease opioid requirement. CONCLUSIONS: New technology
      and new agents allow more rational management of postoperative pain. Use of these
      techniques results in increased patient satisfaction and may improve clinical
      outcome.

PMID- 8304825
TI  - Antioxidants modulate induction of programmed endothelial cell death (apoptosis)
      by endotoxin.
AB  - OBJECTIVE: To evaluate the potential role of reactive oxygen metabolites as
      signals for endothelial cell apoptosis. DESIGN: A series of antioxidants were
      evaluated for their ability to block apoptosis in cultured porcine aortic
      endothelial cells in vitro. RESULTS: Scavenging of the hydroxyl radical with the
      membrane-permeable scavenger dimethyl sulfoxide or blocking its generation via
      the Fenton reaction by the chelation of iron with o-phenanthroline blocked
      apoptosis, whereas the cell membrane-impermeable scavengers superoxide dismutase
      and catalase did not block apoptosis. Inhibition of xanthine oxidase with enzyme
      inhibitory levels of allopurinol also failed to block apoptosis, whereas high
      levels of allopurinol, which also scavenge the hydroxyl radical in vitro,
      conferred protection. In each case (dimethyl sulfoxide, o-phenanthroline, and
      high-dose allopurinol), hydroxyl radical ablation was only effective when
      administered before the priming step (lipopolysaccharide) and was ineffective
      when administered later, prior to the activation step (heat shock). CONCLUSIONS:
      These findings suggest a novel role for the hydroxyl radical as a nonlethal
      intracellular signal in endothelial cell apoptosis. Moreover, the results support
      a role for programmed cell death in the pathogenesis of multiple organ
      dysfunction syndrome and suggest novel strategies for prophylaxis and therapy of
      the most common cause of death in surgical intensive care units.

PMID- 8304826
TI  - Inhibition of nitric oxide synthesis is detrimental during endotoxemia.
AB  - BACKGROUND: Increased production of nitric oxide has been implicated as a
      mediator during septic shock and sepsis syndrome. Inhibition of nitric oxide
      production could be beneficial during endotoxemia to improve the individual's
      hemodynamic status and possibly outcome. OBJECTIVE: To evaluate the effects of
      nitric oxide inhibition on macrophage function and survival in a murine sepsis
      model. DESIGN: Sixty-eight female Swiss-Webster (ND4) mice were injected with a
      sublethal dose of Escherichia coli lipopolysaccharide (25 mg/kg). INTERVENTION:
      The treated group (n = 34) received 10 mg/kg of NG-nitro-L-arginine methyl ester
      at the time of lipopolysaccharide injection. MAIN OUTCOME MEASURES: Blood samples
      and peritoneal macrophages were obtained at baseline and at 2, 4, and 8 hours
      after injection. Nitrite levels were measured in 36 mice from plasma and
      supernatant samples of cultured peritoneal macrophages stimulated with interferon
      gamma (100 micrograms/mL) for 48 hours. Thirty-two animals were observed for
      survival. RESULTS: Administration of N-nitro-L-arginine methyl ester after
      lipopolysaccharide injection caused significant reductions in macrophage mean
      nitrite production from 13 and 15 mumol/L to 7 and 11 mumol/L (P < .05) and
      reduced mean plasma nitrite concentrations from 100 and 118 mumol/L to 46 and 108
      mumol/L (P < .05) at 2 and 4 hours, respectively. The rate of survival was
      significantly decreased to 0% in the group receiving N-nitro-L-arginine methyl
      ester after septic challenge compared with 87.5% in controls (P < .005).
      CONCLUSIONS: Inhibition of nitric oxide production is detrimental in this murine
      model of endotoxemia.

PMID- 8304827
TI  - Efficacy of inhaled nitric oxide in a porcine model of adult respiratory distress
      syndrome.
AB  - OBJECTIVE: To assess the efficacy of inhaled nitric oxide (NO) in reducing
      pulmonary hypertension in a porcine model of adult respiratory distress syndrome.
      DESIGN: Nonrandomized, controlled experiment without blinding. SETTING: Surgical
      research laboratory. PARTICIPANTS: Twelve pigs, matched equally for body weight.
      INTERVENTION: Acute lung injury was induced by intravenous injection of oleic
      acid. Animals were then divided into either a control group, for monitoring
      without any further intervention, or a NO-treatment group, in which NO was
      administered at concentrations of 10 to 80 ppm, with each step separated by a NO
      free interval to assess duration of effect. MAIN OUTCOME MEASURES: Pulmonary
      artery pressure, systemic blood pressure, PaO2, intrapulmonary shunt fraction,
      and extravascular lung water. Nitrosylated hemoglobin, arterial methemoglobin,
      and plasma nitrite and nitrate concentrations. RESULTS: All animals responded to
      oleic acid injection with rapid development of pulmonary hypertension and
      deterioration of PaO2 and intrapulmonary shunt fraction. Inhaled NO reversed
      these changes in a concentration-dependent manner. Cessation of NO administration
      led to a prompt return of pulmonary hypertension. A small but significant drop in
      systemic blood pressure was observed only at the highest concentration of NO
      administered (80 ppm). Extravascular lung water almost doubled following oleic
      acid injury. This increase was sustained in all animals for the remainder of the
      experiment. Significant increases in circulating methemoglobin and plasma nitrite
      and nitrate concentrations were measured during NO inhalation. CONCLUSION:
      Inhaled NO appears to be a selective pulmonary vasodilator and may prove to be
      useful in improving gas exchange in adult respiratory distress syndrome.

PMID- 8304828
TI  - Inhibition of splenic macrophage tumor necrosis factor alpha secretion in vivo by
      antilipopolysaccharide monoclonal antibodies.
AB  - OBJECTIVE: This study tried to determine whether administration of
      antilipopolysaccharide (LPS) murine monoclonal antibody (mAb) 2A3 to mice was
      associated with (1) protective capacity during experimental gram-negative
      bacterial sepsis, and (2) inhibition of tumor necrosis factor alpha (TNF-alpha)
      secretion in the systemic circulation and at the tissue level during experimental
      infection. DESIGN: Mice received an initial intravenous injection of either
      saline or 100 micrograms of anti-LPS mAb 2A3, and 1 hour later underwent
      intraperitoneal inoculation of viable Escherichia coli 0111:B4. Mortality was
      assessed daily for 7 days. Separate groups of mice were treated similarly and
      plasma TNF-alpha concentrations were determined from blood samples obtained at 1,
      3, 6, 10, and 16 hours after infection by enzyme-linked immunosorbent assay.
      Concurrently, splenocytes harvested from animals 3, 10, and 16 hours after
      infection were incubated in culture ex vivo and supernatant TNF-alpha levels were
      determined. RESULTS: Pretreatment with anti-LPS mAb 2A3 prior to an
      intraperitoneal challenge of live E coli 0111:B4 was associated with the
      following: (1) significant protective capacity (100% vs 0% mortality, P < .001);
      (2) inhibition of plasma TNF-alpha levels 16 hours after infection (1257 +/- 323
      pg/mL vs 292 +/- 254 pg/mL, P < .001); and (3) abrogation of TNF-alpha secretion
      derived from splenic macrophages isolated 16 hours after bacterial challenge (229
      +/- 12 pg/mL vs 107 +/- 48 pg/mL, P < .05). CONCLUSIONS: These results strongly
      support the contention that inhibition of LPS-induced TNF-alpha secretion at both
      the tissue and systemic levels is a key mechanism by which anti-LPS mAbs provide
      protection during gram-negative bacterial peritonitis. We believe that in vivo
      monitoring of macrophage cytokine secretion will be critical for elucidating the
      precise role of a variety of mediators in the pathogenesis of gram-negative
      bacterial sepsis.

PMID- 8304829
TI  - Reduced tumor necrosis factor alpha production in lipopolysaccharide-treated
      whole blood from patients in the intensive care unit.
AB  - OBJECTIVE: To determine the cytokine response to lipopolysaccharide in patients
      in the intensive care unit. PATIENTS: Patients in a mixed medical/surgical
      intensive care unit with fever and a de novo clinical dysfunction of at least one
      organ system. METHODS: Whole blood from patients and from laboratory controls was
      stimulated with 8 ng/mL of lipopolysaccharide (Escherichia coli 0111:B4) at 37
      degrees C, and tumor necrosis factor alpha (TNF-alpha) was measured using enzyme
      linked immunosorbent assay at 4, 8, and 24 hours. The same subjects' purified
      monocytes were cultured with 8 ng/mL of lipopolysaccharide in the presence of
      autologous or pooled control plasma or cocultured with purified autologous
      polymorphonuclear leukocytes at a polymorphonuclear leukocyte-monocyte ratio of
      10:1, and TNF-alpha was measured at 24 hours using the enzyme linked
      immunosorbent assay. RESULTS: We detected high (n = 5) and low (n = 5) TNF-alpha
      responders in whole blood producing a mean (+/- SEM) of 27.2 +/- 6.3 pg/mL per
      1000 monocytes vs 0.0 +/- 2.4 pg/mL per 1000 monocytes, respectively (controls,
      58.0 +/- 13.0 pg/mL per 1000 monocytes). The kinetics of TNF-alpha production in
      both groups were comparable. Purified monocytes from both groups of patients
      cultured with lipopolysaccharide alone produced equivalent TNF-alpha values (42.4
      +/- 10.5 vs 40.8 +/- 12.5 pg/mL per 1000 monocytes). Assayable TNF-alpha was not
      different with autologous vs control serum but was markedly diminished by the
      presence of polymorphonuclear leukocytes in patients as well as in controls; the
      two groups of patients did not differ in this polymorphonuclear leukocyte effect.
      CONCLUSION: Lipopolysaccharide stimulation of monocytes in the whole blood
      results in marked variation of TNF-alpha production. This phenomenon may account
      for the variable septic response to infection in patients in the intensive care
      unit.

PMID- 8304830
TI  - Reconstituted high density lipoprotein inhibits physiologic and tumor necrosis
      factor alpha responses to lipopolysaccharide in rabbits.
AB  - OBJECTIVE: To determine the effect of reconstituted human high density
      lipoprotein (rHDL) on physiologic and cytokine responses to infusion of
      lipopolysaccharide. DESIGN: A blinded, randomized trial of three preparations of
      a purified human rHDL with apolipoprotein A-I-phosphatidyl choline-cholesterol
      molar ratios of 1:100:10, 1:150:10, and 1:200:0 and placebo in a rabbit
      lipopolysaccharide intravenous infusion model. INTERVENTIONS: Groups of six New
      Zealand white rabbits received either placebo or one of the three human rHDL
      preparations above as a single, 75-mg/kg (apolipoprotein A-I equivalent) dose
      intravenously over 10 minutes ending 5 minutes before the start of a 3-hour
      infusion of lipopolysaccharide. MAIN OUTCOME MEASURES: Mean arterial pressure,
      base excess, and plasma tumor necrosis factor alpha (TNF-alpha) production were
      determined. RESULTS: The human rHDL suppressed TNF-alpha production with the
      products having the highest fraction of phosphatidyl choline producing the
      greatest suppression of TNF-alpha production. The human rHDL 1:200:0 group
      maintained a low, near-baseline TNF-alpha concentration and minimal decline in
      mean arterial pressure and base excess throughout the lipopolysaccharide infusion
      in contrast to the placebo group. CONCLUSION: Reconstituted human high density
      lipoprotein appears to be useful in inhibiting the physiologic effects and
      cytokine release associated with endotoxemia and may provide adjunctive treatment
      for patients with gram-negative sepsis.

PMID- 8304831
TI  - Endotoxin disrupts beta-adrenergic signal transduction in the heart.
AB  - BACKGROUND: Nonsurvivors of septic shock demonstrate impaired myocardial function
      refractory to the administration of beta-agonists. METHODS: Using the isolated
      rat heart preparation, the integrity of the beta-adrenergic transduction pathway
      was tested (rate pressure product, rate of contraction, rate of relaxation, and
      cyclic adenosine monophosphate content) using isoproterenol hydrochloride (beta
      receptor agonist) or colforsin (forskolin) (adenylyl cyclase activator)
      stimulation following intracoronary endotoxin infusion. RESULTS: Basal rate
      pressure product, rate of contraction, rate of relaxation, and cyclic adenosine
      monophosphate concentrations were unaffected by endotoxin infusion. Endotoxin
      impaired, increases in rate pressure product, rates of contraction and
      relaxation, and cyclic adenosine monophosphate to isoproterenol (P < .05), but
      the response to colforsin was unaffected by endotoxin. CONCLUSIONS: Endotoxin
      disrupts the myocardial response to direct beta-receptor stimulation but not to
      adenylyl cyclase stimulation in the isolated rat heart. CLINICAL RELEVANCE:
      Alteration of the proximal beta-adrenoreceptor complex by endotoxin suggests that
      therapy of the failing heart during refractory septic shock may be directed to
      intact sites distal in the beta-adrenergic pathway.

PMID- 8304832
TI  - Sequential psychomotor skills development in laparoscopic colon surgery.
AB  - OBJECTIVES: To quantify the complexity of each of three skills used in
      laparoscopic colon surgery and to quantify the relative complexity of seven
      laparoscopic colon procedures on a graduated complexity scale. DESIGN: Five
      surgeons used a scale of 1 through 6 to measure the relative complexity of three
      laparoscopic skills (intracorporeal mobilization, intracorporeal
      devascularization, and intracorporeal anastomosis) to assess the relative
      difficulty of seven laparoscopic procedures (right colon resection, sigmoid colon
      resection, low anterior resection, Hartmann's procedure, left colon resection,
      abdominoperineal resection, and transverse colon resection) using detailed
      evaluation of their first 100 laparoscopic colon resections. SETTING: Three
      private community hospitals. MAIN OUTCOME MEASURES: The complexities of
      intracorporeal mobilization, intracorporeal devascularization, and intracoporeal
      anastomosis were recorded for seven laparoscopic colon procedures. RESULTS: The
      least complex procedure was right colon resection, followed in increasing
      complexity by sigmoid colon, Hartmann's procedure, low anterior resection,
      abdominoperineal resection, left colon resection, and transverse colon resection.
      The addition of each laparoscopic skill increased the complexity during each
      procedure. All three skills were not required for every procedure. CONCLUSIONS:
      Since all procedures do not require all three skills, skills can be learned
      sequentially if patients are chosen judiciously. A sequence of laparoscopic
      procedures performed by surgeons is recommended. The relative complexities for
      each procedure suggest an outline (map) for surgeons to use during laparoscopic
      colon surgery.

PMID- 8304833
TI  - A phase II study to evaluate recombinant platelet-derived growth factor-BB in the
      treatment of stage 3 and 4 pressure ulcers.
AB  - OBJECTIVE: To determine the efficacy of the daily topical application of
      recombinant platelet-derived growth factor-BB (rPDGF-BB), a recognized vulnerary
      agent, in the treatment of deep pressure ulcers. DESIGN: Prospective, randomized,
      double-blind trial. SETTING: Patients were treated in a nursing home or a
      hospital setting before transfer to a nursing home. PATIENTS: Eligibility
      criteria included a clean pressure ulcer that had been adequately debrided and
      the absence of severe cardiac, pulmonary, or renal conditions. The causes of the
      ulcers were not related to a venous or arterial vascular disorder. The patients
      were elderly (mean age, 68 to 74 years). INTERVENTIONS: After randomization,
      patients were given daily topical aqueous rPDGF-BB (dosage, 100 or 300
      micrograms/mL) or placebo and saline gauze dressings were applied daily in
      addition to frequent turning. MAIN OUTCOME MEASURE: Serial volume measurements of
      the healing wounds were taken using alginate molds. RESULTS: The ulcers of 41
      patients were analyzed. At the end of 28 days, median ulcer volumes had decreased
      to 83%, 29%, and 40% of the initial size in the groups receiving placebo, rPDGF
      BB, 100 micrograms/dL, and rPDGF-BB, 300 micrograms/mL, respectively. When
      adjusted for initial volume, ulcer volume after 28 days of treatment was smaller
      in the rPDGF-BB-treated groups compared with the placebo group (analysis of
      covariance, P = .056). Ulcers in the two rPDGF-BB-treated groups were
      significantly smaller in volume compared with those in the placebo group, using a
      linear contrast procedure. CONCLUSIONS: Data from this small trial suggest that
      local application of rPDGF-BB may be of therapeutic benefit in accelerating the
      healing of chronic pressure ulcers.

PMID- 8304834
TI  - Hard to swallow test.

PMID- 8304835
TI  - Stroke rehabilitation outcome studies: selection for meta-analysis.

PMID- 8304836
TI  - Betaseron for multiple sclerosis. Implications for therapeutics.

PMID- 8304837
TI  - Value of magnetic resonance imaging-based measurements of hippocampal formations
      in patients with partial epilepsy.
AB  - OBJECTIVE: To determine the occurrence of magnetic resonance imaging-detected
      hippocampal atrophy (HA) in patients with partial epilepsy (temporal and
      extratemporal, cryptogenic, or symptomatic). Magnetic resonance imaging-detected
      HA has been demonstrated to be both sensitive and specific for hippocampal
      sclerosis in cryptogenic temporal lobe epilepsy. DESIGN: Patients' hippocampal
      formations were measured on a computerized system using T1-weighted, 5-mm
      contiguous magnetic resonance coronal images made perpendicular to the
      hippocampus long axis. Hippocampal atrophy was defined on the basis of a
      normative asymmetry index and correlated with the epileptogenic focus defined by
      clinical, electroencephalographic, and magnetic resonance imaging (apart from HA)
      localizing data. PATIENTS AND CONTROL SUBJECTS: Seventy patients with intractable
      complex partial seizures of temporal, extratemporal, or undefined origin and 21
      healthy control subjects. RESULTS: Hippocampal atrophy was present in 70% of
      patients with cryptogenic temporal lobe epilepsy (TLE) (n = 40), 44% of patients
      with symptomatic TLE (n = 9), 29% of patients with extratemporal epilepsy (n =
      14), and 6% of unclassified patients (n = 16). In the cryptogenic TLE category,
      HA was marked and usually concordant (93%) with electroencephalographic
      lateralization. Hippocampal atrophy was often mild in the extratemporal epilepsy
      category. With the use of a wider confidence interval (+/- 3.1 SD instead of +/-
      2.2 SD), HA specificity for TLE increased to 93%, HA specificity for lateralizing
      cryptogenic TLE reached 96%, and HA sensitivity for cryptogenic TLE stood almost
      unchanged (68%). We found a link between early convulsions and HA occurrence.
      CONCLUSIONS: Hippocampal atrophy is a marker for TLE. Dual pathologic findings
      are detected in 44% of symptomatic TLE cases. Mild HA is rarely associated with
      extratemporal epilepsy. Magnetic resonance imaging-based hippocampal volumetric
      analysis is a useful method to localize the origin of partial complex seizures.

PMID- 8304838
TI  - Asymmetric interictal glucose hypometabolism and cognitive performance in
      epileptic patients.
AB  - OBJECTIVE: To relate hemispheric metabolic asymmetries to cognitive performance
      in patients with unilateral mesial temporal lobe epilepsy. DESIGN: Asymmetrical
      cerebral glucose metabolisms on interictal fludeoxyglucose F 18 positron emission
      tomograms (FDG-PET) were correlated with cognitive measures. Analyses included
      partial correlations that controlled for the correlation between metabolic
      asymmetries of the lateral temporal lobe and other brain regions and the
      correlation of IQ scores with affected cognitive scores. SETTING: A university
      epilepsy surgery center. PATIENTS: Subjects included 13 patients who had
      intractable complex partial seizures originating from a mesial temporal lobe.
      INTERVENTION: Patients underwent FDG-PET scanning as part of their diagnostic
      work-up. Asymmetry indexes for cerebral metabolic rates were determined for whole
      hemisphere, lateral temporal lobe, mesial temporal lobe, frontal lobe, thalamus,
      and parietal lobe. MAIN OUTCOME MEASURES: The following cognitive domains were
      assessed: psychometric intelligence, mental control/attention, language, and
      verbal and nonverbal memory. Neuropsychological measures were obtained within 14
      days of FDG-PET scanning. RESULTS: Relative reductions in glucose metabolism of
      the left hemisphere and left lateral temporal lobe correlated with a lower verbal
      IQ score and a lower score on a verbal memory task, recall of logical prose.
      Relative reduction in metabolism of the left side of the thalamus also correlated
      with lower scores for recall of logical prose. CONCLUSION: Relative
      hypometabolism of the left hemisphere correlates with lower cognitive
      performance. Hypometabolism of the left lateral temporal lobe and thalamus
      independently correlates with the verbal memory difficulties seen in this
      epileptic patient population.

PMID- 8304839
TI  - Neuropathologic changes of the temporal pole in Alzheimer's disease and Pick's
      disease.
AB  - OBJECTIVE: To describe the pattern of neuropathologic changes in temporal polar
      cortex in Alzheimer's disease (AD) in comparison with changes in Pick's disease
      (PD) and normal elderly cytoarchitecture. DESIGN: Examination of degenerative
      changes, neurofibrillary tangles, and senile plaques in the temporal poles of 10
      patients with AD, three patients with PD, and five age-compatible control
      subjects, by means of thionein and thioflavine S stains and Alz-50 and ubiquitin
      immunocytochemistry. SUBJECTS: All patients had a documented history of dementia
      and AD or PD confirmed on neuropathologic examination. Control subjects were
      without a history of cognitive impairment or evident neuropathologic changes.
      OUTCOME MEASURES: Cytoarchitecture, neuronal loss, neurofibrillary tangles,
      senile plaques, and Pick bodies. RESULTS: All patients with AD showed atrophy of
      the temporal pole and marked neuronal loss, especially in layers III and V and,
      to a lesser degree, in layers II and VI. Heavy accumulation of neurofibrillary
      tangles was found in layers II, III, V, and VI. Patients with PD showed extensive
      neuron loss throughout, although this appeared to be most prominent in layer III.
      CONCLUSIONS: Both AD and PD pathologic changes severely affect the layers of the
      temporal pole that mediate widespread reciprocal connections with temporal and
      frontal cortices and limbic cortical and subcortical structures. Neural systems
      that interconnect temporal polar cortex with sensory association areas and memory
      related limbic structures are, therefore, disrupted, and it is likely that these
      lesions play a role in the multifaceted cognitive and behavioral changes of AD
      and PD.

PMID- 8304840
TI  - Adrenal size is increased in multiple sclerosis.
AB  - OBJECTIVE: To determine if adrenal glands are enlarged in multiple sclerosis
      (MS). Patients with MS and major depression are insensitive to glucocorticoid
      feedback regulation. Depressed patients have excessively high glucocorticoid
      levels and enlarged adrenal glands. To our knowledge, this is the first study of
      adrenal size in MS. Chronic high levels of adrenal glucocorticoid in MS may
      downregulate responses to exogenous or endogenous steroids. DESIGN: Retrospective
      postmortem analysis compared adrenal size in MS with that in other neurologic and
      non-neurologic diseases. SETTING: Autopsy cases were obtained from the records of
      a tertiary care hospital. PATIENTS: Ten patients had definite MS; 13, amyotrophic
      lateral sclerosis; and 14, acute myocardial infarction. MAIN OUTCOME MEASURES:
      Adrenal and body weight at autopsy. RESULTS: At postmortem examination, the
      adrenal glands of patients with MS were enlarged in comparison with the adrenal
      glands of patients who died of acute myocardial infarction or amyotrophic lateral
      sclerosis. The adrenal glands of the patients with MS were 36% larger than those
      of the patients with amyotrophic lateral sclerosis who had comparable body
      weights. The adrenal-body weight ratio was 40% greater in patients with MS than
      in patients who died of acute myocardial infarction. CONCLUSIONS: The increased
      adrenal size in patients with MS may allow excessive glucocorticoid secretion in
      response to stress and affect immune regulation.

PMID- 8304841
TI  - Depression in complex partial seizures. Electroencephalography and cerebral
      metabolic correlates.
AB  - OBJECTIVE: We sought to determine whether the frequency of depressive disorders
      among patients with complex partial seizures is associated with the laterality of
      ictal onset or the laterality of interictal cerebral hypometabolism. DESIGN:
      Fifty-three patients with medically intractable complex partial seizures were
      assessed for history of interictal depressive disorders meeting strict Diagnostic
      and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R),
      criteria with use of a modification of the Structured Clinical Interview for DSM
      III-R. All subjects underwent video-electroencephalographic telemetry and
      fludeoxyglucose F18 positron emission tomographic scanning. The main outcome
      measure was the frequency of a history of major depressive episodes (MDEs) in
      subjects with left-sided vs right-sided ictal onset and in subjects with left
      sided vs right-sided temporal lobe hypometabolism. RESULTS: Thirty-three subjects
      (62%) had a history of interictal depressive disorders, 16 (30%) of whom met
      criteria for one or more MDEs. More of those with left-sided ictal onset had a
      history of depression. Thirty-six subjects had definite unilateral temporal lobe
      hypometabolism demonstrated by positron emission tomographic scanning. More of
      those with left temporal lobe hypometabolism had a history of MDEs, and the
      combination of left temporal lobe hypometabolism and high-degree hypometabolism
      was strongly associated with a history of MDEs. Furthermore, among those with
      right temporal lobe hypometabolism, more of those with high-degree hypometabolism
      had a history of MDEs. CONCLUSION: Laterality of ictal onset and degree of
      interictal temporal lobe hypometabolism may be interdependent factors that
      contribute to the risk of depressive disorder in patients with complex partial
      seizures.

PMID- 8304842
TI  - Mood changes after surgery for tumors of the cerebral cortex.
AB  - OBJECTIVE: To identify cortical lesion sites associated with particular mood
      states. DESIGN: A prospective study of patients with tumors affecting the
      cerebral cortex. The patients were examined neuropsychologically 1 to 5 days
      preoperatively and 2 to 10 days, several months, and several years
      postoperatively. Only data from the preoperative and the first postoperative
      examination were considered in this report. SETTING: Neurosurgical department of
      the University of Heidelberg (Germany). PATIENTS AND SUBJECTS: A consecutive
      sample of 141 patients with brain tumors (84 female and 57 male) with cortical
      lesions caused by microsurgical tumor resection; 29 clinical control patients
      (having undergone surgery for slipped disks); and 18 normal control subjects.
      MAIN OUTCOME MEASURE: Preoperative and postoperative mood state as measured with
      an adjective checklist. RESULTS: (1) Patients with lesions of the ventral frontal
      cortex or lesions of the temporoparietal cortex reported postoperatively
      significantly (P < .01) worse mood states (anxiety/depression,
      irritability/anger, fatigue) than did patients in the other lesion and control
      groups. (2) A more detailed lesion analysis revealed that lesions of heteromodal
      frontal or parietal association cortexes, combined with paralimbic lesions, were
      responsible for the negative mood states. Lesions of the sensorimotor cortexes
      ameliorated the negative effects of heteromodal and paralimbic lesions. (3)
      Lesion laterality did not influence the mood states. CONCLUSIONS: Heteromodal
      cortexes may be especially concerned with emotionally relevant operations. A loss
      of these functions deprives limbic structures of one of their main sources of
      input and is therefore likely also to produce changes in feelings, that is,
      emotional states.

PMID- 8304843
TI  - Employment following traumatic head injuries.
AB  - OBJECTIVE: Determine rates of, and factors predictive of, return to work in
      patients with civilian traumatic head injuries. DESIGN: Inception cohort study
      with 1- to 2-year follow-up. SETTING: Hospitalized patients in a level I trauma
      center. PATIENTS: Three hundred sixty-six hospitalized head-injured subjects who
      were workers before injury and 95 comparison subjects participated in
      prospective, longitudinal investigations of employment following head injury.
      Head-injured and comparison subjects were similar on basic demographics and
      preinjury employment status. The comparison subjects consisted of patients who
      sustained traumatic injury to the body but not to the head. MAIN OUTCOME MEASURE:
      Time taken to return to work following head injury. RESULTS: Survival methodology
      was used for analysis. Whether patients returned to work and when related to both
      the characteristics of the injured patients (eg, education, preinjury work
      history), the severity of head injury and associated neuropsychologic problems,
      and severity of other system injuries. More precise predictions were possible
      using the multivariate model. CONCLUSIONS: The present study provides a means of
      assessing employment potential predictively. This can be useful for clinical and
      research purposes. The results should be used cautiously and should stimulate
      discussions of appropriate use of services and resources to meet individual
      patients' needs.

PMID- 8304844
TI  - Pleocytosis after status epilepticus.
AB  - OBJECTIVE: To determine the incidence of pleocytosis in patients experiencing
      status epilepticus (SE), regardless of seizure type or cause. DESIGN: A
      retrospective medical chart review. SETTING: Columbia-Presbyterian Medical
      Center, New York, NY. PATIENTS: Of 217 patients seen by the Neurology Service for
      SE during a 3-year period, 138 had a cerebrospinal fluid (CSF) analysis performed
      and were included in the study. All seizure types and etiologies were included.
      MAIN OUTCOME MEASURES: Status epilepticus was defined as a seizure or a series of
      continuing seizures lasting longer than 30 minutes. An abnormal CSF specimen was
      defined as a white blood cell (WBC) count of 6 x 10(6)/L or greater or one or
      more polymorphonuclear leukocytes present. RESULTS: Overall, 22.5% of patients
      demonstrated abnormal WBC count or morphology. There were 21 patients (15%) with
      a WBC count of 6 x 10(6)/L or greater, and another 10 patients with a normal WBC
      count, who had polymorphonuclear leukocytes present. Among patients with
      illnesses usually associated with pleocytosis (such as meningitis or acute head
      trauma), a large proportion had abnormal CSF WBC counts. Among patients with
      conditions usually associated with normal CSF (including idiopathic epilepsy), a
      small proportion had abnormal CSF WBC counts, and the abnormalities were less
      severe. The highest CSF WBC count in patients with no acute insult was 28 x
      10(6)/L. CONCLUSIONS: The most important influence on the CSF WBC count is the
      underlying cause of the SE. Although minor elevations in WBC count can occur
      after SE of any type, pleocytosis should not be attributed to SE alone unless all
      other causes have been eliminated.

PMID- 8304845
TI  - Immunosuppressive treatment of motor neuron syndromes. Attempts to distinguish a
      treatable disorder.
AB  - OBJECTIVE: To determine if response to immunosuppressive treatment in motor
      neuron syndromes could be predicted on the basis of clinical features, anti-GM1
      antibodies, or conduction block. DESIGN: Prospective, uncontrolled, treatment
      trial using prednisone for 4 months followed by intravenous cyclophosphamide (3
      g/m2) continued orally for 6 months. SETTING: All patients were referred to
      university hospital medical centers. PATIENTS: Sixty-five patients with motor
      neuron syndromes were treated with prednisone; 11 patients had elevated GM1
      antibody titers, and 11 patients had conduction block. Forty-five patients
      received cyclophosphamide, eight of whom had elevated GM1 antibodies and 10 had
      conduction block. RESULTS: One patient responded to prednisone, and five patients
      responded to cyclophosphamide treatment. Only patients with a lower motor neuron
      syndrome and conduction block improved with either treatment. Response to
      treatment did not correlate with GM1 antibodies. CONCLUSIONS: GM1 antibodies did
      not serve as a marker for improvement in patients with motor neuron syndrome
      treated with immunosuppressive drugs. Patients with amyotrophic lateral sclerosis
      failed to improve irrespective of laboratory findings.

PMID- 8304846
TI  - National Institutes of Health Consensus Development Conference Statement on
      Acoustic Neuroma, December 11-13, 1991. The Consensus Development Panel.

PMID- 8304848
TI  - Are we effective communicators?

PMID- 8304847
TI  - Are multiple cerebral infarcts synergistic?
AB  - OBJECTIVE: The goal of this study was to characterize the cumulative effects of
      multiple strokes on cognition. DESIGN: We conducted a prospective, longitudinal
      case study with neuropsychological, neurological, and radiological evaluations.
      SETTING: Research was conducted at the Boston (Mass) Veterans Administration
      Medical Center, Neurology Service, on successive inpatient hospital admissions.
      PATIENT: We followed up a 66-year-old right-handed man with multiple subcortical
      lacunae during a 3.5-year period during which he suffered two additional cortical
      infarctions. MAIN OUTCOME MEASURES: Each evaluation included approximately 3
      hours of neuropsychological testing spanning a range of cognitive domains
      (attention, language, memory, visuospatial functions, response inhibition, and
      mental flexibility), full neurological examination, and computed tomographic
      scan. RESULTS: The patient's stepwise cognitive decline was characterized by
      unexpected exacerbation of "frontal" neurobehavioral features following the
      occurrence of two posterior cortical lesions. At initial evaluation, the computed
      tomographic scan showed bilateral subcortical lacunae in basal ganglia and
      periventricular white matter, and symptoms included dysarthria and perseveration.
      The second evaluation, following a left posterior parietal lesion, revealed a
      range of new frontal features, including impulsivity, pull-to-stimulus, and
      difficulty shifting set. Following a subsequent right occipital infarct, further
      frontal lobe impairments emerged: forced grasp reflex and incontinence.
      CONCLUSIONS: We hypothesize that the cumulative effects of infarcts were
      synergistic. That is, the posterior cortical infarcts elicited frontal features
      that would not be expected from a simple sum of these lesions' effects.

PMID- 8304849
TI  - Diagnosing allergies. The hows and whys.
AB  - Allergies are a common problem dealt with in family practice. This article
      reviews the importance of a proper management approach and details the essential
      features in establishing the diagnosis with special emphasis given to the
      importance of good clinical skills.

PMID- 8304850
TI  - Common allergic skin conditions.
AB  - Skin conditions regarded as having an 'allergic' origin are extremely common.
      Immunologically specific hypersensitivities to food and aeroallergens and
      idiosyncratic reactions to food chemicals play a role in some of the individuals
      suffering from these conditions, but in others intrinsic or unknown factors
      dominate. Rashes are frequently seen in relation to food intolerance and adverse
      drug reactions that share common mechanisms.

PMID- 8304851
TI  - Food allergy in children.
AB  - Food allergy is a common condition among infants. The reactions are usually to
      milk, egg and peanut products. They frequently improve with time. It is important
      for the practitioner to recognise the occurrence of these reactions and to advise
      parents of their significance.

PMID- 8304852
TI  - Asthma and allergy. What is the connection?
AB  - Although asthma is a multi-factorial disorder, allergy (immediate
      hypersensitivity) is the most frequent and important factor in initiating airway
      inflammation in young people and is relevant in 94 per cent of asthmatics with an
      onset before the age of 30. After the age of 60, it is a factor in 30 per cent of
      asthmatics. Allergy to the mite, pollens and moulds has been shown to be a major
      risk factor for: development of asthma; chronic persistent asthma; acute attacks
      of asthma; and respiratory arrests due to asthma. All asthmatics must be
      investigated for the presence of allergy. Assessment on the basis of history is
      not accurate enough. Allergy tests are cheap and easily carried out. The
      demonstration of allergy opens up therapeutic strategies that are otherwise
      inappropriate. The simplest and most rational strategy is allergen avoidance. If
      carried out correctly, it is effective. Immunotherapy is an option in
      specifically and carefully selected cases. Anti-allergy measures should be seen
      as an adjunct, not a replacement, to traditional drug therapy. The anti-allergy
      strategies are largely preventive and are a logical component of asthma treatment
      in those asthmatics with evidence of immediate hypersensitivity. The widely used
      regimen of bronchodilator and anti-inflammatory agents should be continued with,
      but is obviously not having the desired impact on morbidity and mortality rates.
      Rational intervention in asthma should combine the two therapeutic approaches.

PMID- 8304853
TI  - Management of allergic rhinitis.
AB  - Allergic rhinitis constitutes one of the commonest causes for visits to a general
      practitioner. An increased understanding of the pathophysiology of the condition
      has led to a more rational use of the pharmacological agents available to treat
      this troublesome condition. Identification of the offending allergens is
      essential if rational approaches to management are to be employed.

PMID- 8304854
TI  - Allergic to the 20th century.
AB  - Twentieth century allergy has caught the popular imagination. This article looks
      at the nature of the problem and whether it is in fact a true allergy. A
      practical approach to clinical assessment is made and advice as to management is
      offered.

PMID- 8304855
TI  - Facilitation for demonstration practice grant holders.
AB  - Our results indicate that most demonstration practice grant holders in South
      Australia and the Northern Territory accept and regularly access facilitator
      services. Grant holders had little experience with granting body procedures and
      most frequently discussed administrative matters regarding their individual
      projects with the facilitator. Concerns about project progress and evaluation
      issues were other popular topics discussed during grant holder facilitator
      interactions. The present study did not seek to measure the impact of
      facilitation on the success of projects. A further study should be undertaken to
      examine the efficacy and effectiveness of facilitation on project outcome.

PMID- 8304856
TI  - Lessons from interpractice visits. Developing standards.
AB  - The author describes a small series of interpractice visits in Perth, Western
      Australia, motivated by the growing need for quality assurance standards in
      general practice. He reviews the strengths and failures of the experience from
      the point of view of doctors equally inexperienced in such ventures.

PMID- 8304857
TI  - A study of the services provided by the women's health nurses in a Sydney Area
      Health Service.
AB  - OBJECTIVES: To describe the client characteristics and nature of services
      provided by women's health nurses and to examine whether the goals set for the
      service are being met. DESIGN: A retrospective study of women's health nurse
      (WHN) records from 1987 to 1991. SETTING AND SUBJECTS: All women attending the
      women's health nurse in the Southern Sydney Area Health Service, 1987 to 1991.
      Older women and women of non English-speaking background are specific targets for
      this service. OUTCOME MEASURES: Pap test and breast self-examination practices
      were examined in relation to age and ethnic background. Use of general
      practitioner services was examined for all women attending the women's health
      nurse in 1991. RESULTS: Forty-five per cent of clients were aged over 50, and 29
      per cent were from a non English-speaking background. Older women were more
      likely to return for subsequent visits to the women's health nurse. The practice
      of breast self-examination increased significantly between visits among all
      women. Forty-one per cent of women had not had a Pap test for at least three
      years, 93 per cent of these women were screened at their first visit. Eighty
      seven per cent of women on their first visit and 86 per cent of women revisiting
      the women's health nurse had seen their general practitioner within the previous
      year. CONCLUSION: Women's health nurses are meeting the goals set for their
      service in relation to health promotion and the screening of women. Their
      services are perceived by their clients as complementary to those provided by
      their general practitioners.

PMID- 8304858
TI  - The management of postnatal depression.
AB  - The author discusses a common yet underdiagnosed problem of the postpartum
      period. Postnatal depression can be severe, with serious consequences for mother,
      child and family. Often, early diagnosis and prompt treatment can be managed in
      general practice. The modern management of postnatal depression is summarised.

PMID- 8304859
TI  - Beyond opportunistic Pap smears in general practice. Women's views of strategies
      to promote regular screening.
AB  - BACKGROUND: An opportunistic reminder for a Pap smear is effective and acceptable
      in general practice. Women's views of strategies to promote ongoing attendance
      for Pap smears were unknown at the time of this study. OBJECTIVE: To determine
      women's perceptions of strategies to help them attend for their next Pap smear.
      SETTING AND PATIENTS: Randomly selected male general practitioners in urban
      Sydney and 174 of their female patients. RESULTS: Seventy-eight per cent response
      rate to a questionnaire sent after a consultation in which opportunistic
      screening was offered. A reminder letter from the GP was nominated as likely to
      help 'a lot' by at least 50 per cent of respondents. Free Pap smears and child
      minding were nominated by at least 50 per cent of respondents as making 'no
      difference'. CONCLUSION: This survey has explored women's perceptions of
      potential strategies to promote continuing Pap smear screening. Given the
      disappointing results when these strategies have been implemented in individual
      general practices, however, the authors recommend prospective controlled
      evaluation before widespread adoption.

PMID- 8304860
TI  - The elderly agoraphobic: a hidden problem.
AB  - This is a fascinating history of an untreated and undiagnosed patient with
      agoraphobia. The limitations to her lifestyle have been extreme. Improvement has
      been impressive and Mrs B is now enjoying her life considerably. The cognitive
      behavioural strategies have been useful and her improvement maintained at follow
      up. Asking elderly patients routine questions to elicit evidence of anxiety,
      phobias, and panic attacks will enable the physician to detect similar cases.

PMID- 8304861
TI  - Dressings and surgical aids.

PMID- 8304862
TI  - Emergency kit for carrying an injectable drug.

PMID- 8304863
TI  - Pointing the finger.

PMID- 8304864
TI  - Treating possible giardiasis.

PMID- 8304865
TI  - Management of concussion.

PMID- 8304866
TI  - CHECK program sample.

PMID- 8304867
TI  - Vulva examination for melanoma.

PMID- 8304868
TI  - Connective tissue disease: an approach.
AB  - The connective tissue diseases are a poorly defined group of conditions
      characterised by abnormal activity of the immune system. This article will not
      detail the features of any one condition, but rather attempt to provide a system
      for the evaluation and classification overall and thus hopefully enable the
      reader to approach these complex conditions with greater confidence.

PMID- 8304869
TI  - Scleroderma.
AB  - Research into the pathogenesis of scleroderma, which may ultimately yield a cure,
      is continuing. In the meantime much can be done for patients presenting with
      scleroderma today. In mild cases reassurance to allay unjustified fears is one of
      the most important aspects of management. In severe cases, the use of
      penicillamine and some of the other available therapies has improved quality of
      life and chances of survival.

PMID- 8304870
TI  - Systemic lupus erythematosus.
AB  - This condition is composed of a collection of signs and symptoms. The diagnosis
      has been made easier by more sensitive laboratory tests, the most important of
      which is still the antinuclear antibody (ANA) test. Prominence is given in this
      article to clinical features and treatment.

PMID- 8304871
TI  - Vasculitis--an overview.
AB  - The systemic vasculitides are a diverse group of conditions surrounded by a
      degree of mythology. Much of the apparent complexity of these disorders is due to
      application of illogical and rigid classification schemes. This overview has
      focused on the need to understand the terminology used to describe the
      vasculitides and their presenting clinical syndromes. The important role of the
      detection of autoantibodies to neutrophil cytoplasmic antigens (ANCA) in the
      diagnostic assessment of patients suspected of having a systemic vasculitis has
      been highlighted. Finally, the replacement of the dogmatic application of
      purportedly 'disease-specific' therapeutic protocols with a balanced assessment
      of the risk-benefit ratio of therapeutic strategies in an individual patient has
      been encouraged.

PMID- 8304872
TI  - Antiphospholipid syndrome. A clearer understanding of an old problem.
AB  - The concept of the antiphospholipid syndrome has only become possible since the
      development of easy to perform solid phase anticardiolipin assays, leading to a
      clarification of the true relationship of a number of otherwise disparate
      clinical features. This review of a multi-factorial problem pays special
      attention to the immunological markers and their significance.

PMID- 8304873
TI  - Juvenile chronic arthritis--diagnosis and management.
AB  - Juvenile chronic arthritis (JCA) is actually a collection of conditions that
      together constitute the major forms of chronic arthritis in childhood. The author
      outlines the diagnosis and management of this condition, which should be
      considered as a distinct entity from the arthritides of adulthood.

PMID- 8304874
TI  - Unexpected effects of a social drug.
AB  - At medical school we are taught that history is 90 per cent of the diagnosis. In
      general practice, with earlier presentation of illnesses it assumes an even
      greater role. This case illustrates the great importance of the history; to make
      the diagnosis, to reduce the cost of investigations and to increase patient
      rapport.

PMID- 8304875
TI  - Twin trouble.

PMID- 8304876
TI  - Inhaled corticosteroids in childhood asthma.
AB  - Practitioners prescribing inhaled corticosteroids for children need to be aware
      of the potential for systemic side effects, particularly in relation to effects
      on growth, bone metabolism and adrenal function. There is a need for further long
      term studies to assess the risk of side effects especially in younger children.
      Until further data are available, caution is required in transposing current
      safety data from adults and older children to the very young. Precise safety
      thresholds cannot be defined at present. The risk-benefit ratio of
      corticosteroids must be assessed for each patient and reassessed at intervals
      during continuing therapy. Strategies to decrease the dose and minimise the
      potential for systemic side effects should be a routine part of asthma
      management. Concern about potential side effects should not outweigh the need for
      effective symptomatic control. Children with asthma should not be exposed to the
      risks of either under treatment or overtreatment of their asthma.

PMID- 8304877
TI  - Gershwin in December.

PMID- 8304878
TI  - Simple scalpel blade holder.

PMID- 8304879
TI  - Dr Ian L Rowe. Learned author and loyal GP.
AB  - Dr Ian Rowe has served medicine in a number of important fields. He has been a
      general practitioner in one community for more than 40 years, he has gained wide
      recognition for his research writings and he has been deeply committed to the
      Royal Australian College of General Practitioners. And he has found time to pass
      on his knowledge to young doctors involved in the RACGP Training Program.

PMID- 8304880
TI  - Treatment of migraine.

PMID- 8304881
TI  - Provision of a community perinatal service in a developing country.

PMID- 8304882
TI  - Education for the management of obstetric conditions in rural general practice. A
      curriculum statement for a major in obstetric studies in the Rural Training
      Programme of the Faculty of Rural Medicine, Royal Australian College of General
      Practitioners.

PMID- 8304883
TI  - Rural obstetrics in NSW.
AB  - Rural general practitioners are responsible for providing obstetric services to
      the majority of women living in rural communities. This paper reports a
      comparison of 5,950 deliveries conducted by rural GPs in NSW during 1990-1991
      with all 88,275 deliveries during the same period in NSW. No evidence that
      obstetric care in accredited rural GP obstetric units is of less than acceptable
      standards could be found. There is scope to increase the use of rural obstetric
      units for the training of future rural GP obstetricians.

PMID- 8304884
TI  - Low birth-weight in NSW, 1987: a population-based study.
AB  - The New South Wales perinatal data collection was used to examine the association
      between low birth-weight and some of its potential risk factors. The study
      population comprised all recorded singleton births to residents of NSW in 1987.
      Low birth-weight infants were categorized as either small for gestational age
      (SGA) or preterm (less than 37 weeks). Risk factors were analyzed separately for
      these categories. The risk factors examined were primarily demographic or
      reproductive history variables. Univariate analysis and multivariate logistic
      regression were used to evaluate the risk factors. The factors associated with
      SGA birth were mainly demographic (maternal age, parity, marital status,
      socioeconomic status, and ethnic group) while those associated with preterm birth
      had more reproductive history variables (maternal age, parity, marital status,
      prior spontaneous abortion, prior induced abortion, prior stillbirth or neonatal
      death, sex of infant). A first antenatal visit after 12 weeks had a statistically
      significant but small effect on both SGA and preterm birth.

PMID- 8304885
TI  - Determinants of birth-weight in women with established and gestational diabetes.
AB  - Increased birth-weight (macrosomia) can complicate the diabetic pregnancy, but
      many factors other than hyperglycaemia can influence birth-weight, in particular
      maternal obesity. In a mixed population (European, Maori and Pacific Islander)
      with a high prevalence of glucose intolerance and obesity we have examined the
      relative impact of various maternal factors on birth-weight in women with both
      established and gestational diabetes. Mean birth-weight was significantly greater
      in women with established or gestational diabetes than in controls (p < 0.0001),
      but was similar in women with gestational and established diabetes, despite
      glycaemic control being significantly poorer (p < 0.0001) in the latter. Birth
      weight closely paralleled prepregnancy body mass index rather than glycaemic
      control, but in Maori women it was lower than expected, probably because of their
      high prevalence of smoking. Daily cigarette consumption was negatively correlated
      with birth-weight (p < 0.01) despite the smokers having significantly poorer
      glycaemic control (p < 0.001). The most significant variables influencing birth
      weight in the diabetic pregnancy were gestational age at delivery, prepregnancy
      body mass index, maternal height, estimated weight gain during pregnancy, the
      presence of hypertension and cigarette smoking (the latter 2 having negative
      effects on birth-weight). Glycaemic control in the last half of pregnancy was not
      significant in this analysis. We conclude that within the limits of glycaemic
      control which we obtained, birth-weight was largely determined by maternal
      factors other than hyperglycaemia. Birth-weight thus has severe limitations as an
      outcome measure of the diabetic pregnancy.

PMID- 8304886
TI  - Pregnancy complicated by the antiphospholipid syndrome.
AB  - A patient with previously undiagnosed antiphospholipid syndrome (APS) developed
      atypical severe preeclampsia at 31 weeks' gestation. Other complications of
      pregnancy included intrauterine growth retardation, thrombocytopenia and fetal
      distress necessitating urgent delivery of a live infant. There was a prior
      history of unexplained jugular venous thrombosis. Prophylaxis against thrombosis
      was commenced immediately postoperatively and no postpartum complications
      occurred. Recent evidence supports the use of antepartum prophylaxis with low
      dose heparin in patients with APS. The role of low dose aspirin, either alone or
      in combination with heparin, is yet to be determined. Human immunoglobulin may be
      useful in selected cases. Early diagnosis is a key factor in their management.

PMID- 8304887
TI  - Fetal blood sampling and its complications related to the indications for fetal
      blood sampling.
AB  - A prospective study on fetal blood sampling (FBS) was conducted in the
      Fetomaternal Medicine Division of the Department of Obstetrics and Gynaecology at
      the National University Hospital, Singapore. FBS was performed on 159 occasions
      in 156 women between January, 1988 and December, 1991. The aim of this study was
      to identify the factors that were associated with an adverse outcome following
      the procedure. Twenty four abnormal pregnancies were terminated; of the remaining
      132 desired pregnancies the overall pregnancy loss was 44 (33.3%), which included
      those within 2 weeks and those after 2 weeks of the procedure and neonatal
      deaths. Fetal loss occurring within 2 weeks of the procedure is considered a
      procedure-related loss which occurred in 19 (14.3%) of the 132 pregnancies. When
      the fetal loss occurred within 2 weeks of the procedure 89% had a major
      abnormality on ultrasonographic scanning. The conclusion from our study is that
      the risks of FBS were increased in abnormal pregnancies, most likely due to the
      underlying pathology.

PMID- 8304888
TI  - Choroid plexus cysts in the fetal brain.
AB  - Choroid plexus cysts may be detected in the fetal choroid plexus on routine
      second trimester ultrasound scanning. The presence of these cysts is associated
      with trisomy 18 (Edward syndrome) in 3.47% of cases and with trisomy 21 (Down
      syndrome) in 0.46% of cases. The cysts themselves almost always disappear by 23
      weeks and are thought to be a normal developmental variant. The world literature
      experience would indicate that the size of the choroid plexus cyst and the
      presence of bilateral cysts has no bearing on the magnitude of risk of
      chromosomal abnormality; 76% of babies with trisomy 18 also have other dysmorphic
      features which may be detectable by ultrasound. It is strongly advised that
      genetic counselling be undertaken and amniocentesis be considered when choroid
      plexus cysts are identified in the fetus.

PMID- 8304889
TI  - Randomized, double blind, placebo controlled comparison of ritodrine and
      hexoprenaline for tocolysis prior to external cephalic version at term.
AB  - External cephalic versions in the study period were performed in a double blind
      design by 2 experienced practitioners. Sixty-three patients were allocated to
      treatment with either placebo, ritodrine or hexoprenaline. The main outcome
      measure studied was successful completion of external cephalic version.
      Hexoprenaline, but not ritodrine, was statistically more likely to be associated
      with successful version than placebo (p = 0.04 versus p = 0.22).

PMID- 8304890
TI  - Epidural analgesia and fetal heart rate abnormalities.
AB  - Lumbar epidural analgesia is frequently associated with fetal heart rate
      abnormalities. Fluid preloading prior to the procedure significantly reduces the
      incidence of abnormal fetal heart rate patterns (p = 0.02). The mechanisms of
      these changes are discussed and the importance of maternal hypotension is
      evaluated. Fluid preloading and continuous electronic fetal monitoring should be
      considered routine for all women undergoing this procedure.

PMID- 8304891
TI  - Should assessment of amniotic fluid volume form an integral part of antenatal
      fetal surveillance of high risk pregnancy?
AB  - This study was conducted to evaluate the role of the Amniotic Fluid Index (AFI),
      used along with nonstress cardiotocography (NST) and fetal acoustic stimulation
      test (FAST), when required, in prediction of adverse pregnancy outcome. Over a 3
      year period 565 pregnant women had antepartum fetal surveillance due to various
      high risk pregnancy factors and delivered within 7 days of the test. Antepartum
      fetal surveillance included nonstress cardiotocography together with estimation
      of AFI. Need for induction of labour, presence of meconium at rupture of
      membranes, Caesarean section for fetal distress, Apgar score at 5 minutes, need
      for neonatal endotracheal intubation, admission to neonatal special care unit and
      perinatal death were the main outcome measures. Nonreactive nonstress tests and
      Caesarean sections for fetal distress were more common and neonatal outcome was
      significantly poorer in patients with AFI < 5 cm than in those with higher AFI
      values. Of the 4 perinatal deaths in the group with AFI < 5 cm, 3 had a reactive
      NST within 7 days of fetal death. It is concluded that pregnancy outcome is often
      poor in the presence of very low AFI and in these cases a reactive NST loses its
      usual reassuring value. It is suggested that AFI estimation should be included as
      an integral part of antepartum fetal surveillance of high risk pregnancies.

PMID- 8304892
TI  - Autologous predeposit blood donation in pregnancy--a perspective.

PMID- 8304893
TI  - Urinary calcium/creatinine ratio in the prediction of preeclampsia.
AB  - The prediction of preeclampsia by the urinary calcium/creatinine ratio during the
      early third trimester was assessed in 190 primigravidas, aged less than 35 years
      and between 28 and 32 weeks' gestation without pregnancy complications.
      Preeclampsia developed in 6.8% of the patients. The mean maternal age,
      gestational age at entry into the study and at delivery, and the average mean
      arterial blood pressure at entry into the study did not differ significantly
      between the 13 patients with subsequent preeclampsia and the 177 normotensive
      patients. The patients with preeclampsia did not have significantly less
      excretion of calcium than the normotensives.

PMID- 8304894
TI  - Caesarean section anaesthesia and the Apgar score.
AB  - Retrospective comparison of epidural and general anaesthesia by a multivariate
      analysis of 1 and 5 minute Apgar scores did not show that general anaesthesia
      improves operating conditions for Caesarean section or reduces fetal trauma for
      preterm and term infants.

PMID- 8304895
TI  - Cervical ripening induces labour through interleukin 1 beta.
AB  - In order to study the Interleukin 1 beta (IL-1 beta) levels in mechanical
      cervical ripening with Foley catheter, IL-1 beta levels in amniotic fluid of 12
      women before and after cervical ripening were compared with those in 23 women in
      spontaneous active labour. IL-1 beta was present in 81.8% of patients after
      cervical ripening and in none prior to it. In women with spontaneous labour 69.6%
      had immunodetectable IL-1 beta. Women with spontaneous labour and those sampled
      after cervical ripening had similar IL-1 beta levels in the amniotic fluid.
      Cervical ripening with Foley catheter is associated with high levels of IL-1 beta
      and this probably induces labour.

PMID- 8304896
TI  - Efficacy of large loop excision of the transformation zone for cervical
      intraepithelial neoplasia.
AB  - This study showed the efficacy of large loop excision of the transformation zone
      (LLETZ) in the management of cervical intraepithelial neoplasia (CIN). Eighty
      three women with abnormal cervical cytology were recruited. Colposcopic
      examination and directed punch biopsy were performed and the women had LLETZ
      therapy as an outpatient procedure. There were 2 cases of microinvasive cervical
      carcinoma that were missed by directed punch biopsy, the diagnosis being made
      after the patients underwent LLETZ treatment. There was a large disparity in the
      histological analysis between directed punch biopsy and LLETZ specimen. This
      disparity would not have been detected if the women were treated by ablative
      methods. In women with cervical dysplasia, LLETZ procedure is preferred as the
      whole excised lesion can be examined histologically and diagnostic error is
      reduced.

PMID- 8304897
TI  - Laparoscopic hysterectomy--a technique.
AB  - A technique for the performance of laparoscopic hysterectomy (laparoscopic
      assisted vaginal hysterectomy) is described. There are particular advantages to
      the patient in using this technique. There are also social and financial
      advantages. It is envisaged that this technique will become part of the routine
      surgical armamentarium of the gynaecological surgeon, whose personality disposes
      him towards this type of surgery. A prediction is made as to the future use of
      this surgical technique.

PMID- 8304898
TI  - Laparoscopic removal of endometriosis in the pouch of Douglas.
AB  - Twenty-six patients with endometriosis in the pouch of Douglas were treated by
      laparoscopic excisional surgery; previous medical and surgical therapy had failed
      in 24 of them. Endometriosis in the pouch of Douglas occurred infrequently in
      association with bladder or ovarian endometriosis. Coital and rectal pain were
      markedly reduced or cured 6 months after surgery in all except 2 patients.
      Laparoscopic surgical excision of endometriosis is indicated when drug or other
      surgical treatments fail and may avoid the need for hysterectomy in some
      patients.

PMID- 8304899
TI  - Posthysterectomy rectal and vaginal prolapse, a commonly overlooked problem.
AB  - The existence of combined rectal and vaginal prolapse is more common than the
      literature would suggest. This paper outlines a further development in the
      operative management which has been applied to 24 patients with this problem. All
      had had a hysterectomy and most had had in addition one or more vaginal repairs.
      The common mode of presentation was one of pelvic pain (19 patients), sometimes
      severe, crippling and intractable and some form of protrusion (14 patients),
      difficult or unsatisfied defaecation and rectal incontinence (9 patients). The
      vaginal prolapse which always involved the vault and usually involved the lower
      vagina was usually found to be incomplete and the rectal prolapse complete (but
      occult). The operative procedure essentially consists of a Wells type rectopexy
      which has a new modification in which the sling is extended to anchor the vaginal
      vault after correction of the enterocele by the abdominal approach. A vaginal
      repair is subsequently performed at the same operation where anterior or
      posterior vaginal prolapse persists. Important points in the procedure are the
      avoidance of sepsis (the vaginal vault is not opened during the procedure) and
      protection of the ureters by careful assessment of the lateral margins of the
      vaginal vault which is illuminated by transvaginal vault endoscopy. At this early
      stage operative morbidity has been minimal, relief of the pelvic symptoms has
      been most encouraging, but the length of follow-up is short (range 6-30 months,
      average 15.6) and long-term evaluation will be necessary as with all surgery for
      prolapse.

PMID- 8304900
TI  - A comparison of early pregnancy failure and ongoing pregnancy rates between fresh
      and frozen embryo transfer following in vitro fertilization.
AB  - In order to compare pregnancy outcomes following fresh and frozen embryo transfer
      after in vitro fertilization (IVF), a retrospective analysis of data from the
      Royal North Shore IVF Programme was performed. Six hundred and sixty seven embryo
      transfers following routine IVF were performed during 1991 and 1992. Four hundred
      and twenty fresh embryo transfers were performed during that period, resulting in
      a clinical pregnancy rate of 21%. In comparison, 247 frozen transfers, where the
      initial procedure was routine IVF, were performed, resulting in a clinical
      pregnancy rate of 16.6%. This difference was not significant. When varying
      numbers of transferred embryos in the 2 groups were taken into account, there was
      a significant difference in the proportion of ongoing viable fetuses per embryo
      returned for 1991, but not for 1992. Although there were a greater number of
      abortions and ectopic pregnancies in the fresh transfer group, these differences
      did not achieve statistical significance. The implications of improving results
      from frozen embryo transfer are discussed.

PMID- 8304901
TI  - Serial human chorionic gonadotrophin determination in the diagnosis of ectopic
      pregnancy.
AB  - Serial human chorionic gonadotrophin (HCG) determinations were made in 21
      patients with ectopic pregnancy (EUP) and in 29 patients with early intrauterine
      pregnancy (IUP) to examine the increase in HCG values. The median slope of the
      HCG rise for the patients with EUP was 116 IU/1/2 days and 4,220 IU/1/2 days in
      patients with IUP. The slopes were significantly different (p < 0.05). Using a
      discrimination limit of 980 IU/1/2 days, the predictive value of a slope below
      this limit was 90% in EUP compared to the control group of intrauterine
      pregnancies. Determination of the slope of HCG rise may be of value in early
      recognition of ectopic pregnancy in patients with increasing HCG levels below the
      ultrasonographic discriminatory zone. An international agreement on
      discrimination limits and unity of HCG algorithms is suggested.

PMID- 8304902
TI  - Bilateral tubal pregnancies after pronuclear stage embryo tubal transfer to 1
      tube.

PMID- 8304903
TI  - A pregnancy after planned partial endometrial resection.
AB  - A 28-week pregnancy is reported after a planned partial endometrial resection in
      an infertile patient. The fetus died 32 hours after birth because of prematurity
      consequent to premature membrane rupture and premature labour. A partial placenta
      accreta was dealt with at Caesarean section. Complete endometrial resection may
      not be required to cure menorrhagia. It may be possible to control menorrhagia by
      targeting specific areas of endometrium associated with menorrhagia. Fertility
      may be retained by leaving the fundal and peritubal endometrium. The increased
      risks of pregnancy complications following endometrial resection suggest that
      more information is required to design endometrial resection so as to both cure
      menorrhagia and to sustain successful pregnancy.

PMID- 8304904
TI  - Biopsy diagnosis and conservative surgical treatment of adenomyosis.
AB  - Fifteen patients with dysmenorrhoea and menorrhagia refractory to medical
      treatment were referred for surgical treatment. Pre-operative diagnosis of
      adenomyosis was suggested by vaginal ultrasound in 13 patients and was confirmed
      pre-operatively by myometrial biopsy in 5 and by transcervical myometrial biopsy
      at the time of endometrial resection in 7. Conservative surgery included
      endometrial resection (7), myometrial reduction by electrocautery (4), and
      myometrial excision (3). Marked improvement occurred in 4 of 7 patients after
      endometrial resection, 3 of 4 after myometrial reduction, and all of 3 having
      myometrial excision. Diagnosis of adenomyosis is improved by use of vaginal
      ultrasound and percutaneous or transcervical myometrial biopsy. Conservative
      surgical procedures including endometrial resection and myometrial reduction or
      excision may reduce the need for hysterectomy in the presence of adenomyosis.

PMID- 8304905
TI  - Stomas and pregnancy.
AB  - Few obstetricians have much experience of the pregnant patient with a stoma. This
      paper was prompted by the management of 3 such patients in as many months and
      reviews the limited literature on stomas and pregnancy.

PMID- 8304906
TI  - An Australian experience of transdermal oestradiol patches in a subtropical
      climate.
AB  - Tolerability and efficacy of transdermal oestradiol patches were assessed in 121
      menopausal women over a period of 3 months to 2.5 years. Of particular interest,
      in a subtropical climate such as Brisbane, were the problems associated with
      adhesiveness and skin irritation during the summer months. We conducted a
      retrospective study with self-administered questionnaires. All patients had been
      selected for the nonoral route because of side-effects or relative
      contraindications to oral therapy. There was, overall, good efficacy and
      acceptability. The majority of the women found the patch very adequate in
      relieving symptoms of the menopause (vasomotor, genitourinary and
      musculoskeletal). Most preferred the patch to oral therapy. The oestradiol patch
      was well tolerated and few side-effects were reported. Breast tenderness and
      weight gain were 2 minor problems associated with its use. Skin irritation was
      minimal, but adhesiveness was a problem during the summer months, especially with
      swimming or showering. Some practical suggestions were obtained about how to
      overcome site of application problems.

PMID- 8304907
TI  - A case of multicentric glandular tumorigenesis of the female upper genital tract:
      implications for management.

PMID- 8304908
TI  - Family planning practices among Lebanese, Turkish and Vietnamese women in Sydney.

PMID- 8304909
TI  - Risk factors and a risk scoring system for the prediction of malignancy in
      ovarian cysts.

PMID- 8304910
TI  - Another use for the laparoscope and the dangers of using loose swabs at surgery.

PMID- 8304911
TI  - Insulin action and substrate competition.
AB  - An increased supply of FFAs for oxidation leads to a reduced rate of glucose
      oxidation and interferes with the inhibitory action of insulin on hepatic glucose
      production. Available evidence indicates that in humans skeletal muscle is a site
      for such substrate competition, which involves both pyruvate oxidation and
      glycogen synthesis. The insulin resistance of obesity is thought to be mostly of
      metabolic origin, and fully reversible. A reduction in FFA supply by weight
      reduction can, however, reverse this defect. The insulin resistance associated
      with NIDDM is thought to be primary, with a strong genetic basis, and partially
      irreversible. Patients with NIDDM are unable to increase their glucose oxidation
      normally in response to insulin to meet the energy demands of the body. Increased
      oxidation of lipids represents a compensatory phenomenon to meet these demands.
      Therapeutic use of the glucose-FFA cycle to lower blood glucose levels has
      yielded conflicting results. Studies are in progress to develop agents that
      inhibit gluconeogenesis by interfering with FFA oxidation. Nicotinic acid
      derivatives seem to enhance glycogen synthesis acutely by activating glycogen
      synthetase. Whether these or similar agents can be used to restore impaired
      glycogen synthesis, the most characteristic genetic defect in NIDDM, cannot be
      answered until the effect has been proven in chronic studies. The existence of
      substrate competition between amino acids and glucose, and an intrinsic
      hypoaminoacidaemic property of amino acids, makes it possible to expand the
      Randel cycle into a glucose-FFA-amino acid cycle, which integrates control of
      substrate disposition at the whole body level.

PMID- 8304912
TI  - Genetics of insulin action.
AB  - Insulin action is highly likely to be primarily genetically determined (given a
      permissive or facilitative environment, for example sufficient calorie
      availability), as shown by variations in ethnic distribution, evidence for
      familial transmission and genotypic responses to experimentally induced metabolic
      stresses. Further, it is likely that the genetic predisposition to insulin
      resistance is closely linked to (or perhaps synonymous with) the predisposition
      to develop overt NIDDM. Alternatively, in the development of diabetes, the
      genetic basis for insulin resistance may be necessary, but not sufficient,
      requiring a second major gene for beta-cell vulnerability (e.g. exhaustion,
      deterioration of function, amyloid deposition). The future examination of the
      genetics of insulin action depends in large measure on the method of assessment
      of insulin action that is selected and its consistent application to individuals,
      families and populations. The phenomenological approaches currently being used to
      describe and define insulin resistance could be identifying many different
      disorders, all leading to an apparent decrease or impairment of insulin action
      compared with that in 'normals'. Selection of any method for determining the
      presence of insulin resistance, together with selection of the threshold for
      'present versus absent' is, at best, difficult. It is further complicated by the
      frequent association of insulin resistance with a wide range of disturbances,
      including hypertension, dyslipidaemia and glucose intolerance--the insulin
      resistance 'syndrome'. A number of possible loci and candidate genes controlling
      insulin action have been studied, and most have been ruled out as the probable
      underlying cause of the majority of cases of defective insulin action. Among
      those genes that are unlikely to be determinants of insulin resistance (except in
      a few rare cases of mutations) are those for insulin, the insulin receptor,
      glucose transporters and the genes for many specific enzymes. While these are
      unlikely to be responsible for insulin resistance, such potential genetic defects
      cannot be fully excluded using present methods. Direct gene sequencing of
      polymerase-chain-reaction amplified DNA may be the ultimate approach to
      identifying the critical defects underlying insulin resistance. Other candidate
      genes regulating insulin action are likely soon to come forth, such as those
      controlling the generation and function of the intracellular mediators of insulin
      action.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8304913
TI  - Insulin resistance and risk factors for coronary heart disease.
AB  - In this presentation an effort has been made to review the impact of resistance
      to insulin-mediated glucose uptake and/or hyperinsulinaemia on various metabolic
      end-points and clinical syndromes. Insulin resistance is present in the great
      majority of patients with states of glucose intolerance, but frank decompensation
      of glucose homoeostasis does not occur if individuals can maintain a state of
      compensatory hyperinsulinaemia. Although compensatory hyperinsulinaemia may
      prevent the development of NIDDM in insulin-resistant individuals, there is
      substantial evidence that insulin resistance and/or hyperinsulinaemia is
      associated with higher plasma concentrations of triglyceride, uric acid and
      plasminogen activator inhibitor 1 and with lower HDL cholesterol concentrations.
      Obesity, decreased physical activity and possibly cigarette smoking accentuate
      the degree of insulin resistance and its manifestations, and a genetic basis is
      also involved. Resistance to insulin-mediated glucose uptake and/or
      hyperinsulinaemia have been shown to be associated with high blood pressure,
      microvascular angina and CHD. Thus, resistance to insulin-mediated glucose uptake
      is a common phenomenon, which makes a major contribution to the aetiology and
      clinical course of common and serious diseases. Based on the above
      considerations, it is difficult to over-emphasize the health-related implication
      of a defect in insulin-mediated glucose uptake.

PMID- 8304915
TI  - Cellular insulin action and insulin resistance.

PMID- 8304914
TI  - Relationship between insulin resistance and coronary heart disease in diabetes
      mellitus and the general population: a critical appraisal.
AB  - The hypothesis that a causal relationship exists between insulin resistance and
      atherogenesis was first proposed over 23 years ago, and has given rise to a vast
      literature. Biological plausibility has been lent to the hypothesis by studies in
      which insulin has produced some effects in cell and tissue culture, and in vivo
      in arterial tissue, consistent with our understanding of the pathogenesis of
      atherosclerosis. Clinical studies demonstrating a complex interrelationship
      between insulin resistance-hyperinsulinaemia and established risk factors for CHD
      -hypertension, hypertriglyceridaemia, low HDL cholesterol levels and abdominal
      obesity--are reviewed. A review of the studies examining an independent
      association between hyperinsulinaemia and coronary heart disease is presented.
      Cross-sectional studies in both the general population and diabetes support the
      relationship; however, prospective studies in the general population provide
      limited and inconsistent support for this hypothesis and highlight the
      confounding effects of blood pressure, dyslipidaemia and obesity on the effects
      of hyperinsulinaemia. In subjects with NIDDM and impaired glucose tolerance,
      prospective studies have not shown a deleterious effect of insulin treatment per
      se, nor have they consistently shown a significantly increased risk for those
      with higher endogenous insulin levels. The therapeutic implications of the
      evidence to date are less complex and involve weight reduction by diet and
      exercise, the lowering of elevated blood pressure with metabolically neutral
      agents, the judicious use of lipid lowering drugs and, in diabetes, the use of
      insulin where clinically indicated.

PMID- 8304916
TI  - Hepatic glucose metabolism and insulin resistance in NIDDM and obesity.

PMID- 8304917
TI  - Action of insulin on glucose metabolism in vivo.
AB  - Insulin plays a key role in the maintenance of normal glucose tolerance by
      suppressing endogenous glucose production during a meal. Insulin is not, however,
      involved in the regulation of splanchnic glucose uptake. The latter process
      appears, based on studies performed in dogs, to be regulated primarily by the
      arterial-portal glucose gradient and to a smaller extent by glucose mass-action.
      Regarding peripheral glucose utilization, insulin is not needed to maintain a
      normal rate of glucose utilization since this can also be achieved by
      hyperglycaemia and glucose mass-action. Insulin is, however, necessary for the
      maintenance of normal rates of glucose oxidation and storage in insulin-sensitive
      tissues, and for the prevention of excessive gluconeogenic substrate production.

PMID- 8304918
TI  - In vivo glucose transport in human skeletal muscle: tools, problems and
      perspectives.

PMID- 8304919
TI  - Cardiovascular actions of insulin in humans. Implications for insulin sensitivity
      and vascular tone.
AB  - Insulin has a plethora of actions, most of which are initiated after interaction
      with its specific cell surface receptor on classical target tissues. Prominent
      among these actions is its ability to increase cellular permeability to glucose
      in muscle and fat. Heretofore, the cardiovascular actions of insulin in humans
      have received little attention. The effects of insulin on the cardiovascular
      system and, in particular, on skeletal muscle vasculature are physiological,
      specific, co-ordinated and appear to play an integral part in its overall action
      to promote the disposal of glucose and probably other substrates. The vascular
      actions of insulin should be added to the long list of actions initiated by this
      hormone, and are important to consider in the study of in vivo metabolism in
      health and disease.

PMID- 8304920
TI  - Insulin action on protein metabolism.
AB  - On the basis of the preceding observations, the following sequence of events can
      be postulated during insulin deficiency or excess. The main feature of insulin
      deficiency is the disruption of protein balance in muscle that rapidly leads to
      emaciation and wasting. Muscle protein degradation is greatly enhanced while
      increased amino acid availability maintains protein synthesis. In splanchnic
      tissues, both degradation and synthesis are increased but with an altered
      pattern, so that the levels of some proteins are increased (e.g. proteins of the
      acute-phase response), while those of others are decreased (e.g. albumin). As a
      result, intracellular protein content in liver is maintained but secretion of
      plasma proteins is abnormal. In healthy subjects, an acute increase in insulin
      concentration, as occurs after a meal, leads to a rapid suppression of protein
      breakdown in the splanchnic area. If hyperinsulinaemia is not supported by an
      exogenous amino acid supply, as might occur during a protein-free meal or
      experimentally during euglycaemic hyperinsulinaemic clamping, the plasma as well
      as muscle free amino acid concentration drops, owing to reduced splanchnic
      release. With reduced amino acid availability, insulin is not anabolic in muscle.
      If amino acid concentrations are maintained at normal or high levels, e.g.
      following a mixed meal, a net protein deposition in muscle may occur, primarily
      because of a stimulation of synthesis and possibly owing to inhibition of
      breakdown.

PMID- 8304921
TI  - Mechanisms of antimutagenesis and anticarcinogenesis: role in primary prevention.

PMID- 8304922
TI  - Extrapolation of in vitro antimutagenicity to the in vivo situation: the case for
      anthraflavic acid.

PMID- 8304923
TI  - Preventive effect of magnesium hydroxide on carcinogen-induced large bowel
      carcinogenesis in rats.
AB  - Preventive effect of magnesium hydroxide on carcinogen-induced, large bowel
      carcinogenesis was examined in three experiments using F344 rats. Experiment I:
      Rats received dietary administration of magnesium hydroxide at concentrations of
      500 or 1,000 ppm after treatment with methylazoxymethanol (MAM) acetate (25
      mg/kg, 3 times). These rats had a lower incidence of large bowel neoplasms than
      animals given MAM acetate alone. Reduction of the tumor incidence was especially
      significant at a dose of 500 ppm. Experiment II: Rats given magnesium hydroxide
      (250, 500, or 1,000 ppm) together with 1,2-dimethylhydrazine (DMH) (20 mg/kg, 10
      times) showed a lower multiplicity of large bowel tumors than those given DMH
      alone. Experiment III: The labeling indices of the cryptal cells of the large
      bowel (cecum or proximal colon or distal colon) or rates given magnesium
      hydroxide for 4, 6, or 8 weeks after treatment with MAM acetate (25 mg/kg, 3
      times) were smaller than those of animals given MAM acetate alone, indicating
      that magnesium hydroxide suppressed, carcinogen-induced epithelial cell (large
      bowel) proliferation. The results of the three experiments suggest that
      magnesium, one of the essential metals, is a promising chemopreventive agent in
      humans.

PMID- 8304925
TI  - Chemoprotection by inducers of electrophile detoxication enzymes.

PMID- 8304924
TI  - Antimutagenic investigations on commercial yogurt.

PMID- 8304926
TI  - Protective role of glutathione, thiols, and analogues in mutagenesis and
      carcinogenesis.

PMID- 8304927
TI  - Sulfotransferase- and acetyltransferase-mediated activation of carcinogenic N
      hydroxyarylamines in mammals and bacteria, and their modulation by thiols.

PMID- 8304928
TI  - Multiple mechanisms: the example of vitamin A.
AB  - It has become evident that retinoids control differentiation, embryonal
      development, and tumorigenesis. In animal models, skin tumorigenesis has been
      shown to be prevented by retinoids, which in this organ function as antitumor
      promoters in the two-stage system using 7,12-dimethylbenz(a)anthracene (DMBA) as
      the initiator, and 12-tetradecanoyl-phorbol-13-acetate (TPA) as tumor promoter.
      Even though pharmacological doses applied topically appear to inhibit tumor
      formation, we found that papilloma and keratoacanthoma growth required
      physiological concentrations of retinoic acid and that vitamin A deficiency was
      even more effective than excess retinoid in inhibiting SENCAR mouse skin
      tumorigenesis. In human beings, oral administration of retinoic acid after tumor
      resection was effective in inhibiting the appearance of new tumors on the skin of
      four patients with Xeroderma Pigmentosum, and was effective in preventing new
      primary tumor formations in patients treated for head and neck cancer. The newly
      discovered nuclear receptors for retinoic acid function as transcriptional
      activators for several genes. In patients with acute promyelocytic leukemia
      presenting with a reciprocal translocation of chromosome 17 to chromosome 15, the
      breakpoint has been identified in the retinoic acid receptor alpha gene, which
      forms a fusion gene with a new gene termed myl, on chromosome 15. Treatment of
      the patients with retinoic acid causes complete remission of the APL. It also
      appears to generate cells that do not bear the translocation. Therefore,
      retinoids may well function as modulators of carcinogenesis both at the promotion
      level as well as by causing differentiation of neoplastically transformed cells.

PMID- 8304930
TI  - Organ-specific modification of carcinogenesis by antioxidants in rats.

PMID- 8304929
TI  - Induction of rat liver GSH transferases by 1,2-dithiole-3-thione illustrates both
      anticarcinogenic and tumor-promoting properties.

PMID- 8304931
TI  - The modulating effects of antioxidants in rat embryos and Sertoli cells in
      culture.
AB  - The male and female reproductive systems are targets for the toxicity of a wide
      range of compounds. There is a paucity of information regarding the modulating
      effects of antioxidants in such systems. Enzymically generated oxygen radicals
      have been shown to be toxic and/or mutagenic in a variety of in vitro test
      systems. It is known that vitamins C and E can modify responses in such systems.
      Malformations and growth reductions have been observed in whole rat embryo
      cultures in this laboratory after treatment with the oxygen radical generating
      system of xanthine/xanthine oxidase. Groups of 9.5-day-old rat embryos were
      treated with this system with or without vitamin C or E. Vitamin C at the doses
      given totally abolished neural suture defects while vitamin E only partially did
      so. Vitamins C and E administered alone had no effect on the embryos. Germ cell
      detachment has been shown to occur in mixed cultures of Sertoli and germ cells in
      response to some known in vivo testicular toxins. Such cultures were also treated
      with the oxygen radical generating system of xanthine/xanthine oxidase. There was
      an increase in germ cell detachment with this treatment which was reduced by
      vitamin C but not by vitamin E at the doses administered. These findings would
      suggest that vitamin supplementation could protect somatic cells of reproductive
      systems against toxins that act through oxygen radical mechanisms.

PMID- 8304932
TI  - Blocking the plant activation of promutagenic aromatic amines by peroxidase
      inhibitors.

PMID- 8304933
TI  - Chemoprevention of rat liver carcinogenesis by S-adenosyl-L-methionine: is DNA
      methylation involved?

PMID- 8304934
TI  - Molecular control of human papillomavirus RNA expression in neoplasia.

PMID- 8304935
TI  - The two umuDC-like operons, samAB and umuDCST, in Salmonella typhimurium: the
      umuDCST operon may reduce UV-mutagenesis-promoting ability of the samAB operon.

PMID- 8304936
TI  - Formation, inhibition of formation, and repair of oxidative 8-hydroxyguanine DNA
      damage.

PMID- 8304937
TI  - Modulation by retinoic acid of spontaneous and benzo(a)pyrene-induced c-Ha-ras
      expression.
AB  - The effects of retinoic acid on the expression of the Ha-ras gene were studied in
      transformed rat hepatoma cells (H4IIE) and in rat aortic smooth muscle cells
      (ASMC) treated with benzo(a)pyrene (30 microM) in vitro. In H4IIE cells, a dose
      dependent increase in steady state Ha-ras mRNA levels was observed upon exposure
      to retinoic acid for 24 hr. Exposure of ASMC to 10 microM retinoic acid under
      similar experimental conditions was also associated with increased Ha-ras
      expression. In contrast, retinoic acid (1 and 10 microM) inhibited benzo(a)pyrene
      induced expression of Ha-ras in ASMC. These results suggest that retinoic acid
      modulates spontaneous and carcinogen-induced expression of Ha-ras in a
      differential manner.

PMID- 8304938
TI  - Identification of natural antimutagens with modulating effects on DNA repair.
AB  - The results of a study of bioantimutagenesis, with emphasis on natural
      antimutagens from plant extracts with modulating effects on DNA repair in
      Escherichia coli bacteria are presented in this chapter. Comparative screening
      for spontaneous or induced mutagenesis, as well as expression of the SOS gene,
      sfiA was accomplished. Antimutagenic capacity was obtained with nontoxic
      concentrations of the plant extracts; the same plant extract may decrease or
      increase the mutation rate, or even be ineffective, depending on the bacterial
      strain used and the concentration of the extract applied. Since antimutagenic
      effects may be the consequence of either stimulation of error-free repair,
      inhibition of error-prone repair, or involvement of multiple mechanisms, the
      effects of several plant extracts on the level of UV-induced beta-galactosidase
      were screened (to monitor SOS induction in cells). Reduction of the enzyme
      activity induced by UV was observed following addition of St. John's wort
      extract, while there was not reduction after thyme, aloe, camomile, or lime-tree
      and the level of UV-induced enzyme was even higher with sage extract. Our results
      indicate that the antimutagenic effect of St. John's wort is probably due to
      suppression of error-prone repair. Moreover, we assume that an antimutagenic
      effect obtained with thyme, mint, and sage under certain conditions may be due to
      enhanced error-free repair.

PMID- 8304939
TI  - Inhibition of nitrosation.
AB  - Humans are exposed through ingestion or inhalation to preformed N-nitroso
      compounds (NOC) in the environment and through the endogenous nitrosation of
      amino precursors in the body. Activated macrophages and bacterial strains
      isolated from human infections can enzymatically produce nitrosating agents and
      NOC from precursors at neutral pH. As a consequence, endogenous nitrosation may
      occur at various sites of the body, such as the oral cavity, stomach, urinary
      bladder, and at other sites of infection or inflammation. Numerous substances to
      which humans are exposed have been identified and shown to inhibit formation of
      NOC. Such inhibitors include vitamins C and E, certain phenolic compounds, and
      complex mixtures such as fruit and vegetable juices or other plant extracts.
      Nitrosation inhibitors normally destroy the nitrosating agents and, thus, act as
      competitors for the amino compound that serves as substrate for the nitrosating
      species. Independently, epidemiological studies have already established that
      fresh fruits and vegetables that are sources of vitamin C, other vitamins, and
      polyphenols have a protective effect against cancers at various sites and in
      particular gastric cancer. This article briefly reviews (a) the chemistry of NOC
      formation and inhibition; (b) the studies in experimental animals that showed
      that inhibition of endogenous NOC synthesis leads to a reduction of toxic,
      mutagenic, and carcinogenic effects; (c) recent studies in humans where the
      degree of inhibition of endogenous NOC synthesis was directly quantified; and (d)
      the possible contribution of nitrosation inhibitors to human cancer prevention.

PMID- 8304940
TI  - Mechanisms of inhibition of tumor progression.

PMID- 8304941
TI  - Histopathology of human intraepithelial neoplasia with implications for
      chemoprevention strategy.

PMID- 8304942
TI  - Potential mechanisms of antitumorigenesis by protease inhibitors.
AB  - The mechanisms by which protease inhibitors suppress carcinogenesis are unknown.
      From our studies, we believe the first event in carcinogenesis is a high
      frequency epigenetic event and that a later event (presumably genetic) leads to
      the malignant state. Protease inhibitors appear to be capable of reversing the
      "initiating" event in carcinogenesis, even at long times after carcinogen
      exposure. Protease inhibitors are thought to stop an ongoing process begun by
      carcinogen exposure. Effects of protease inhibitors on the following phenomena
      are thought to be related to their anticarcinogenic activity: 1) ability to
      effect the expression of certain oncogenes, and 2) ability to return carcinogen
      increased levels of certain proteolytic activities (e.g., Boc-val-pro-arg-MCA
      hydrolyzing activity) to normal levels. Other effects of anticarcinogenic
      protease inhibitors have also been observed; for example, we have reported that
      they can bring carcinogen-induced, elevated levels of gene amplification to
      nearly normal levels. The mechanism(s) by which protease inhibitors suppress
      carcinogenesis will not be determined with certainty until the mechanisms
      involved in cancer induction are known.

PMID- 8304943
TI  - cDNA cloning of serine/threonine phosphatase catalytic subunits and reversion of
      the malignant phenotype to the normal phenotype by okadaic acid, a protein
      phosphatase inhibitor.

PMID- 8304944
TI  - Mechanisms of action of new antitumor promoters.

PMID- 8304945
TI  - Murine alpha/beta interferons inhibit benzo(a)pyrene activation and mutagenesis
      in mice.
AB  - In addition to their antiviral and immune regulatory properties, interferons
      (IFNs) are known to depress hepatic cytochrome P450-dependent metabolism. As many
      chemical mutagens and carcinogens require bioactivation by the mixed-function
      monooxygenase (MFO) system in order to be genotoxic, a combined genetic and
      biochemical approach was used to establish whether IFNs could inhibit the
      activation of benzo(a)pyrene (BaP) to the ultimate clastogenic metabolite(s) in
      vivo. Treatment of mice with murine IFN-alpha/beta depressed cytochrome P450
      content, as well as ethoxyresorufin O-deethylase activity (EROD), as a probe of
      class IA1 P450 isozymes, for 24 hrs and delayed the attainment of normal levels
      to approximately 30 hrs. After IFNs plus BaP treatment, EROD activity showed a
      reduction up to 70% after 24 hrs with an enhancement in activity at 30 hrs. A
      positive correlation exists between the rate of inhibition of oxidative BaP
      hepatic metabolism and inhibition of clastogenic effects in vivo, as scored in
      the bone marrow chromosome aberration assay.

PMID- 8304946
TI  - Direct interception of mutagens and carcinogens by biomolecules.
AB  - Five points are emphasized: 1. Chemical interception and mere physical exclusion
      of mutagens and carcinogens constitute the major means by which mutations in
      cellular DNA are prevented. DNA repair processes comprise critical, but
      relatively minor, modes of genetic protection. 2. Disruption of a mutagen
      interception defense mechanism can lead to substantial increases in mutagenesis
      and can preordain sites to eventual tumor formation. 3. Quantitation of the
      relative contributions of various blocking molecules is often simplified by the
      fact that protection can be calculated merely through knowledge of the measured
      concentration of the antimutagen and its rate of reaction with specific mutagens
      as measured in straightforward in vitro tests. 4. Two recently recognized
      defensive molecules, carnosine and ergothioneine, are put ++forward as examples
      of interesting chemical interceptor molecules. 5. Essentially all antimutagens
      are in fact "double-edged swords." Situations can be artificially constructed
      that can lead to generation of toxic species from molecules that are normally
      antimutagens; in isolated cases some of these interactions can be pictured as
      having deleterious consequences in vivo. This may be one reason why a number of
      important antimutagens are often sequestered, either in different tissues or by
      binding to dispensable macromolecules.

PMID- 8304948
TI  - Recent results in preclinical and clinical drug development of chemopreventive
      agents at the National Cancer Institute.

PMID- 8304947
TI  - Sphingolipids inhibit multistage carcinogenesis and protein kinase C.

PMID- 8304949
TI  - Dietary inhibitors against mutagenesis and carcinogenesis.

PMID- 8304950
TI  - Oxidants and mitogenesis as causes of mutation and cancer: the influence of diet.
AB  - A very high level oxidative damage to DNA occurs during normal metabolism. In
      each rat cell, the steady-state level of this damage is estimated to be about
      10(6) oxidative adducts, and about 10(5) new adducts are formed daily. This
      endogenous DNA damage appears to be a major contributor to cancer and aging. The
      oxidative damage rate in mammalian species with a high metabolic rate, short life
      span, and high age-specific cancer rate such as in rats is much higher than the
      rate in humans, long-lived mammals with a lower metabolic rate, and a lower age
      specific cancer rate. It is argued that deficiency of micronutrients, that
      protect against oxidative DNA damage, is a major contributor to human cancer.
      Epidemiological studies, a large body of experimental evidence, and theoretical
      work on the mechanisms of carcinogenesis point to mitogenesis as a major
      contributor to cancer. Dividing cells, compared to nondividing cells, are at an
      increased risk for mutations due to: 1.) conversion of DNA adducts to mutations;
      2.) chance of mitotic recombination, gene conversion, and nondisjunction; and,
      3.) increased exposure of DNA to mutagens. Mitogenesis also increases the
      probability of gene amplification and loss of 5-methylcytosine. Dietary
      interventions that lower mitogenesis, such as calorie restriction, decrease
      cancer incidence.

PMID- 8304951
TI  - The growth of preneoplastic lesions by 1,2-dimethylhydrazine in rat colon is
      inhibited by dietary starch.
AB  - The effect of dietary starch and sucrose on colon proliferation and the growth of
      foci of dysplastic crypts in the colon (FDC) were studied in female Sprague
      Dawley rats, treated p.o. with 1,2-dimethylhydrazine (DMH). The animals were fed
      for 30 and 105 days with high fat (23% w/w corn oil) diets in which carbohydrates
      were represented by corn starch (starch diet) or sucrose (sucrose diet) (46%
      w/w). After 105 days of feeding, proliferation was markedly reduced in animals
      fed the starch diet. The number of FDC was not significantly affected by dietary
      treatments. However, after 30 and 105 days the percent of small FDC (formed by
      one-two dysplastic crypts) was higher in the animals fed the starch diet when
      compared to the sucrose diet. In the cecum of the animals fed the starch diet the
      percent of butyrate, propionic, isovaleric, and valeric over total short-chain
      fatty acids (SCFA) was increased, whereas the percent of acetic acid was
      decreased. Cecal pH was also decreased in the animals fed starch. The results
      suggest that starch diets have a protective role against DMH-colon carcinogenesis
      in the rat, mediated by a drop in cecal pH and an increased concentration of some
      SCFA.

PMID- 8304952
TI  - Prevention of genotoxic effects by dietary constituents in various organs of mice
      treated with nitrosamines.

PMID- 8304953
TI  - Protective mechanisms of dietary fibers in nutritional carcinogenesis.
AB  - Fibers in foods are complex carbohydrates. There are several types of fiber, but,
      for the purpose of mechanistic insight into their mode of protective action in
      carcinogenesis, classification into two broad types, soluble and insoluble
      fibers, is warranted. Soluble fibers are present in fruits, vegetables, and
      certain grains like oats. This type of fiber undergoes metabolism in the small
      intestine and especially in the large intestine through bacterial enzymes,
      converting it to products that increase stool size only moderately. But, they
      have appreciable effects in modifying the metabolism of colon carcinogens like
      azoxymethane to yield detoxified products and, thus, reducing colon
      carcinogenesis. In contrast, insoluble fibers present in sizeable amounts in bran
      cereals, like wheat or rice, are not significantly metabolized by enzymes in the
      intestinal flora. Such fibers increase stool size substantially through several
      mechanisms, including higher water retention. The larger bulk dilutes
      carcinogens, especially tumor promoters such as secondary bile acids, resulting
      in lower risk of colon cancer in animals and in humans. Evidence in animal models
      and in humans also indicates that fiber may lower the risk of breast cancer,
      possibly via an endocrine mechanism. Based on these concepts, increased intake of
      total fiber, but especially of wheat bran cereal fiber, to yield a daily stool in
      adults of about 200 grams can significantly reduce the risk of colon cancer and,
      to a lesser but definite extent, of breast cancer. Thus, adequate fiber intake
      from cereals, fruits, and vegetables can help prevent important types of human
      cancer.

PMID- 8304954
TI  - Effect of antioxidant supplementation in an elderly population.

PMID- 8304955
TI  - Spontaneous mutations and fidelogens.

PMID- 8304956
TI  - Extracellular interception of mutagens.
AB  - Extracellular interception of mutagens by excreted enzymes or by chemical agents
      that react with or bind to formed mutagens provides an important means of defense
      against chemical mutagens/carcinogens. Kada and Shimoi have classified molecules
      that function in this manner as "desmutagens," and many of them are natural
      cellular metabolites. Among the specific mechanisms that such agents may employ
      are: prevention of the activation of "promutagens" to mutagens; stimulation of
      enzymes (e.g., glutathione-S-transferase) that catalyze the binding/inactivation
      of damaging electrophiles; direct binding and concomitant inactivation of
      promutagens or mutagens; interference with uptake of mutagens into cells; etc. De
      Flora and Ramel have provided an excellent discussion of the mechanisms of these
      agents and a proposed classification scheme. Drawing on work from our own
      laboratories and other recent examples in the literature, several examples of
      mechanistic approaches to these studies using natural plant-derived materials,
      e.g., humic acid, Glycyrrhiza glabra extract, glutathione, and bioflavonoids, are
      also described. Antioxidants and agents that conjugate electrophiles will be
      among the modes of action described for obtaining the goal of intercepting
      mutagens/carcinogens.

PMID- 8304957
TI  - Proteins as scavengers of nitrite: antimutagenic implications.

PMID- 8304958
TI  - Antimutagenic agents from natural products of terrestrial and marine origin.

PMID- 8304959
TI  - Inhibitory effects of dietary leafy vegetables on mutagens and on active oxygens.

PMID- 8304960
TI  - Antiviral activity of 2',3'-dideoxy-beta-L-5-fluorocytidine (beta-L-FddC) and
      2',3'-dideoxy-beta-L-cytidine (beta-L-ddC) against hepatitis B virus and human
      immunodeficiency virus type 1 in vitro.
AB  - 2',3'-Dideoxy-beta-L-5-fluorocytidine (beta-L-FddC) and 2',3'-dideoxy-beta-L
      cytidine (beta-L-ddC), two nucleosides with "unnatural L-configuration," have
      been synthesized and found to have potent antiviral activity against hepatitis B
      virus (HBV) and human immunodeficiency virus type 1 (HIV-1) in vitro with very
      little toxicity. At 1 microM, both beta-L-ddC and beta-L-FddC inhibited the
      growth of HBV by more than 90%, while at the same concentration the D
      configuration counterparts, 2',3'-dideoxy-beta-D-cytidine (ddC) and 2',3'-dideoxy
      beta-D-5-fluorocytidine (beta-D-FddC), did not show antiviral activity against
      HBV. The order of anti-HIV-1 activity was beta-L-FddC > ddC; beta-D-FddC > beta-L
      ddC. The dose-limiting toxicity of ddC is neuropathy which is believed to be
      caused by the inhibition of the synthesis of mitochondrial DNA. ddC severely
      inhibited the mitochondrial DNA synthesis of CEM cells yielding an IC50 value of
      0.022 microM. Conversely, both beta-L-FddC and beta-L-ddC did not demonstrate any
      inhibition against mitochondrial DNA synthesis up to 100 microM concentration.

PMID- 8304961
TI  - Isoproterenol interacts differently with beta-adrenoceptors in astrocytes and
      neurons isolated from the adult rat brain.
AB  - The interaction of isoproterenol with beta-adrenoceptors has been investigated in
      astroglial and neuronal cells isolated from adult rat cerebral cortices. Using
      the non-selective beta-adrenergic antagonist (3H)CGP-12177 as a ligand, binding
      experiments revealed that both types of cells exhibit beta-adrenoceptors. However
      the analysis of the isoproterenol displacement curve indicated that only neuronal
      cells contained the high affinity conformational state of the beta-adrenoceptor.

PMID- 8304962
TI  - Interpretation and analysis of receptor binding experiments which yield non
      linear Scatchard plots and binding constants dependent upon receptor
      concentration.
AB  - Receptor-binding assays with radiolabelled ligands are widely used to evaluate
      the biological activity of drugs and hormones. The affinity, usually expressed as
      the dissociation constant (Kd), and the capacity (Bmax) of the receptor
      preparation for various ligands are determined in order to compare quantitatively
      various agonists and antagonists. Experiments with the same ligand and receptor,
      however, often yield rather disparate values for these binding parameters. One
      obvious reason for variability in Kd is that straight lines are fitted to data
      that are clearly curved. Another and more serious reason is that a ligand's
      apparent dissociation constant decreases when the receptor preparation is diluted
      and so experiments done at different receptor concentrations do not give
      identical results. We demonstrate that both of these observations, i.e. the
      effect of receptor concentration and the curvature of Scatchard plots, can be
      explained by the presence of a competitive inhibitor in the receptor preparation,
      a possibility which is not normally considered in the analysis and interpretation
      of receptor binding assays. We show that the apparent Kd obtained by the
      conventional one- or two-site analysis may be several orders of magnitude larger
      than the true dissociation constant and the affinity is therefore seriously
      underestimated. Application of a model, which assumes that an inhibitor is
      present in the receptor preparation, will improve the quantitative determination
      of Kd and Bmax significantly. As a simple alternative method we explain how the
      apparent binding parameters obtained by the conventional method should be
      interpreted and how they can be used to estimate the true affinity, provided
      sufficiently low concentration data are available.

PMID- 8304963
TI  - Changes in nuclear chromatin precede internucleosomal DNA cleavage in the
      induction of apoptosis by etoposide.
AB  - Etoposide, a DNA topoisomerase II inhibitor, caused a concentration-dependent
      induction of apoptosis in immature thymocytes. Using a flow cytometric method to
      separate and quantify normal and apoptotic cells, etoposide-induced apoptosis was
      inhibited by cycloheximide and actinomycin D but not by zinc. Etoposide induced a
      marked cleavage of DNA into nucleosomal length fragments or multiples thereof,
      which was completely inhibited if the thymocytes were also incubated in the
      presence of zinc. Etoposide, alone, induced the classical ultrastructural
      features of apoptosis, but in the presence of zinc, the morphological pattern was
      markedly different and dominated by discrete clumps of condensed chromatin
      abutting the nuclear membrane. These latter changes resemble those described as
      the earliest changes in apoptosis. These results support the hypothesis that, in
      the induction of apoptosis, critical alterations in nuclear chromatin occur prior
      to endonuclease cleavage of DNA into nucleosomal fragments.

PMID- 8304964
TI  - Tamoxifen inhibits growth of oestrogen receptor-negative A549 cells.
AB  - The non-steroidal anti-oestrogen tamoxifen inhibits proliferation of the A549
      human lung adenocarcinoma cell line (EC50 congruent to 10 nM) yet there was no
      evidence of oestrogen receptor expression as determined by ligand binding assay
      and northern blotting. 17-beta-Oestradiol had no effect on A549 cell
      proliferation (1 pM-1 microM) and moreover a 100-fold excess failed to reverse
      the effect of 10 nM tamoxifen as did a 100-fold excess of the steroidal anti
      oestrogens ICI 164384 and ICI 182780. However, 4-hydroxytamoxifen which had no
      significant effect on A549 cell growth (1 pM-1 microM) completely antagonized the
      effect of 10 nM tamoxifen when used at a 100-fold excess. In the presence of
      oleic acid and stearic acid (10 microM) the growth inhibitory effect of tamoxifen
      in A549 cells was greatly enhanced, unlike effects mediated by the anti-oestrogen
      binding protein described in other cells where these fatty acids had no effect.
      These results indicate the presence of a unique and highly sensitive mechanism in
      A549 cells whereby concentrations of tamoxifen relevant to classical receptor
      binding can inhibit cell growth in the absence of the oestrogen receptor.

PMID- 8304965
TI  - Differential effects of the pyrimido-pyrimidine derivatives, dipyridamole and
      mopidamol, on platelet and vascular cyclooxygenase activity.
AB  - The chronic administration of 10 mg/kg/day of dipyridamole to rats produced 33.7%
      inhibition of platelet aggregation induced with ADP and a 93% increase in 6-keto
      prostaglandin F1 alpha (6-keto-PGF1 alpha) in vascular samples, versus saline
      treated rats. Mopidamol, 8.3 mg/kg/day, caused 50.6% inhibition of ADP-induced
      platelet aggregation, 37.6% inhibition of aggregation induced with arachidonic
      acid, a 47.6% decrease in serum levels of thromboxane B2 and a 23.7% increase in
      the vascular production of 6-keto-PGF1 alpha, versus saline-treated rats.
      Dipyridamole showed a higher in vitro anti-aggregating effect in whole blood
      (IC50 6.6 microM) than in platelet-rich plasma (PRP) (IC50 210 microM), when ADP
      was used as inducer, and had no effect in the presence of arachidonic acid.
      Mopidamol exerted a similar effect in whole blood (IC50 3.7-20 microM, depending
      on the inducer) and PRP (IC50 11-17.3 microM), and showed a dose-dependent
      inhibition of platelet aggregation and thromboxane B2 synthesis induced with
      arachidonic acid (IC50 16.8-22.3 microM). Mopidamol also inhibited enzymatically
      induced lipid peroxidation) (IC50 89 +/- 5.9 mumol/L) and had no effect on free
      radical-induced lipid peroxidation. The dose-dependent increase in 6-keto-PGF1
      alpha in vascular samples after incubation with dipyridamole showed a negative
      linear correlation with inhibition of lipid peroxidation (r2 = 0.77). It is
      concluded that the phosphodiesterase inhibitors, dipyridamole and mopidamol,
      interfere in a different manner with platelet function. It seems that mopidamol
      may also exert a selective effect on platelet thromboxane synthesis.

PMID- 8304966
TI  - Lipid hydroperoxide induced mitochondrial dysfunction following acute ethanol
      intoxication in rats. The critical role for mitochondrial reduced glutathione.
AB  - It has been found that acute ethanol (EtOH) intoxication of rats caused depletion
      of mitochondrial reduced glutathione (GSH) of approximately 40%. A GSH reduction
      of similar extent was also observed after the administration to rats of
      buthionine sulphoximine (BSO), a specific inhibitor of GSH synthesis. Combined
      treatment with BSO plus EtOH further decreased mitochondrial GSH up to 70% in
      comparison to control. Normal functional efficiency was encountered in BSO
      treated mitochondria, as evaluated by membrane potential measurements during a
      complete cycle of phosphorylation. In contrast a partial loss of coupled
      functions occurred in mitochondria from EtOH- and BSO plus EtOH-treated rats. The
      presence in the incubation system of either GSH methyl monoester (GSH-EE), which
      normalizes GSH levels, or of EGTA, which chelates the available Ca2+, partially
      restores the mitochondrial phosphorylative efficiency. Following EtOH and BSO
      plus EtOH intoxication, the presence of fatty-acid-conjugated diene
      hydroperoxides, such as octadecadienoic acid hydroperoxide (HPODE), was detected
      in the mitochondrial membrane. Exogenous HPODE, when added to BSO-treated
      mitochondria, induced, in a concentration-dependent system, membrane potential
      derangement. The presence of either GSH-EE or EGTA fully prevented a drop in
      membrane potential. The results obtained suggest that fatty acid hydroperoxides,
      endogenously formed during EtOH metabolism, brought about non-specific
      permeability changes in the mitochondrial inner membrane whose extent was
      strictly dependent on the level of mitochondrial GSH.

PMID- 8304967
TI  - Characterization of vasoactive intestinal peptide receptors in canine liver
      membranes.
AB  - The binding characteristics of vasoactive intestinal peptide (VIP) in the liver
      membranes of the dog were examined using radioligand binding assay with 125I-VIP
      and unlabelled peptides and results were compared with those from the rat. The
      binding of VIP to canine liver membranes occurred in a reversible, saturable,
      specific and temperature-dependent manner. Guanine nucleotides dose-dependently
      inhibited VIP binding. The order of potency in competition experiments with
      unlabelled peptide was: VIP > pituitary adenylate cyclase activating peptide
      (PACAP)-27 > PACAP-38 >> peptide histidine isoleucine (PHI) = secretin in the
      dog, and PACAP-27 > PACAP-38 > VIP > PHI > secretin in the rat. PHI and secretin
      were about 5000 times less potent than VIP in the dog, but secretin was about 100
      times less potent than VIP in the rat. The VIP binding sites in canine liver
      membranes have recognition sites for VIP which differ from those in rat liver
      membranes. As most of VIP in the portal vein was removed during its passage
      through the canine liver, the binding sites of canine liver may play a role in
      degradation of VIP.

PMID- 8304968
TI  - Trimethadione metabolism, a useful indicator for assessing hepatic drug-oxidizing
      capacity.
AB  - The metabolism of trimethadione (TMO), a useful indicator of hepatic drug
      oxidizing capacity in rats and humans, was studied using 14 different forms of
      rat cytochrome P450 (CYP1A1, 1A2, 2A1, 2A2, 2B1, 2B2, 2C6, 2C7, 2C11, 2C12, 2C13,
      2E1, 3A2 and 4A2) and three forms of human cytochrome P450 (CYP1A2, 2C and 3A4).
      TMO N-demethylation was increased by treating rats with phenobarbital. CYP2C11
      and 2B1 had high TMO N-demethylase activity, but 1A1 and 1A2 had low activity.
      Antibodies raised to CYP2C11 and 2B1/2 inhibited TMO N-demethylation in hepatic
      microsomes of untreated and phenobarbital-treated rats, respectively. In a
      reconstituted system, human CYP3A4 and 2C produced efficiently dimethadione
      (DMO), but CYP1A2 did not catalyse TMO N-demethylation. Antibodies raised to
      CYP3A2 and 2C11 inhibited TMO N-demethylation in human hepatic microsomes. These
      results indicated that the N-demethylation of TMO is catalysed mainly by CYP2C11
      and 2B1 in rat hepatic microsomes, and that human CYP3A4 and an unspecified
      isoform of the 2C subfamilies contribute to TMO N-demethylation in human liver.

PMID- 8304969
TI  - Antileishmanial activity and modification of hepatic xenobiotic metabolizing
      enzymes in golden hamster by 2(3)-tert-butyl-4-hydroxyanisole following infection
      with Leishmania donovani.
AB  - Butylated hydroxyanisole (BHA) inhibited the growth of Leishmania donovani
      promastigotes (strain AG83) in vitro. The inhibition was dose dependent: the
      concentration of BHA required for 50% inhibition of the rate of growth was 1
      microgram/mL. BHA also prevented growth of L. donovani in vivo in golden hamsters
      infected with L. donovani. In addition, the effect of BHA on several enzymes
      involved in the metabolism of xenobiotics both in uninfected animals and animals
      infected with L. donovani is reported.

PMID- 8304970
TI  - Identification of a multidrug resistance modulator with clinical potential by
      analysis of synergistic activity in vitro, toxicity in vivo and growth delay in a
      solid human tumour xenograft.
AB  - Circumvention of multidrug resistance in vitro by resistance modulators is well
      documented but their clinical use may be limited by effects on normal tissues. We
      have compared four resistance modifiers, both in terms of modulation of
      doxorubicin sensitivity in vitro and toxicity in vivo, in order to determine
      whether it is possible to select agents with clinical potential. Verapamil, D
      verapamil and quinidine are all maximally active in the multidrug resistant cell
      line at about 7 microM and are not cytotoxic at this concentration. The tiapamil
      analogue Ro11-2933 is a highly potent resistance modulator such that at only 2
      microM sensitization is greater than is seen with the other modulators at 7
      microM. Since the ID50 concentration for Ro11-2933 is 17.7 microM (5-12-fold less
      than the other modifiers) we have used isobologram analysis to demonstrate that
      the interaction with doxorubicin is supra-additive and cannot be explained by
      additive toxicity. This method of analysis also revealed that when resistance
      modulation is related to the cytotoxicity of the modulator itself, all four
      modulators show comparable activity. On the other hand, measurement of the acute
      toxicity in mice of the modulators did reveal differences. The LD10 for verapamil
      (51 mg/kg) was about one third of that for quinidine (185 mg/kg) and this is
      consistent with the known maximum tolerated plasma levels in patients.
      Furthermore, whilst epirubicin alone was unable to reduce the growth rate of a
      multidrug resistant human tumour xenograft, the addition of quinidine, but not
      verapamil, at the maximum tolerated dose did do so. D-Verapamil was only about
      half as toxic as racemic verapamil and this too is consistent with clinical
      observations. The LD10 for Ro11-2933 (152 mg/kg) was comparable with that for
      quinidine. In the human tumour xenograft model maximal growth inhibition was
      observed with the combination of epirubicin and Ro11-2933 (45 mg/kg) and this
      degree of growth inhibition was comparable to that obtained with epirubicin alone
      in the drug sensitive xerografts. Ro11-2933 had no measurable effects on the
      plasma or tumour pharmacokinetics of epirubicin. These results suggest that it is
      possible to predict the clinical potential of a resistance modulator.
      Furthermore, Ro11-2933 is a promising agent for use in the clinic since maximal
      resistance modulation in vivo is observed at about one third of the LD10 dose.

PMID- 8304972
TI  - Adrenoceptor-mediated cardiac and vascular responses in hypothyroid rats.
AB  - This study has investigated adrenoceptor-mediated responses and beta
      adrenoceptors in neonatal-onset hypothyroidism in rats. Four groups of adult rats
      were studied: controls, neonatal-onset uncorrected hypothyroidism (continuous
      oral methimazole treatment) and after chronic triiodothyronine (T3) replacement
      of these rats at either 25 or 100 micrograms/kg/day for 8 weeks beginning at 12
      weeks of age. Hypothyroid rats were 61% smaller with an 18% decrease in heart
      rate; food and water intake were reduced to 43% and 52%, respectively; O2
      consumption was reduced to 20% and rectal temperature was 2.9 degrees lower. T3
      administration increased body weight to 60-62% of controls; metabolic changes
      were reversed; but tachycardia and cardiac hypertrophy (60-120% increases)
      resulted. The positive inotropic responses to the selective alpha 1-adrenoceptor
      agonist, phenylephrine, in left ventricular papillary muscles were abolished; the
      beta 1-adrenoceptor agonist, noradrenaline, was significantly less potent as an
      inotropic compound in isolated cardiac tissues from hypothyroid rats. The potency
      of phenylephrine to contract thoracic aortic rings was reduced in hypothyroid
      rats. These changes in alpha- and beta-adrenoceptor mediated responses were
      reversed by T3 administration. Both beta 1- and beta 2-adrenoceptor densities
      were increased in the hypothyroid left ventricle; T3 administration further
      increased beta 1-adrenoceptor density. We conclude that neonatal hypothyroidism
      produces pronounced physiological responses, changes in adrenoceptor-mediated
      responses and an increased ventricular beta 1-adrenoceptor density. T3
      replacement reversed the changes in cardiac responses and metabolic parameters,
      except body weight, but produced cardiac symptoms of hyperthyroidism
      (tachycardia, hypertrophy as well as an increased beta 1-adrenoceptor density).

PMID- 8304971
TI  - The microsomal dealkylation of N,N-dialkylbenzamides.
AB  - The in vitro metabolism of N,N-dialkylamides by phenobarbital-induced rat liver
      microsomes yields an N-alkylamide and the corresponding aldehyde. Although, N
      hydroxymethyl-N-alkylamide intermediates can be detected from N-methyl-N
      alkylamides, no N-hydroxyalkyl-N-alkylamide intermediates are detected from the
      N,N-dialkylamide substrates. Vmax values were independent of amide structure,
      whereas Vmax/Km values were dependent on the lipophilicity of the N,N
      dialkylbenazamide studied. These results suggest that diffusion of substrate into
      the membrane-bound enzyme active site limits the rate of microsomal oxidation of
      the amides. Metabolism of N-alkyl-N-methylamides reveals identical values of Vmax
      for demethylation and dealkylation. Values of Vmax/Km for demethylation depend
      upon the lipophilicity of the N-alkyl group, whereas Vmax/Km values for
      dealkylation appear to be dependent upon the steric bulk of the alkyl group,
      particularly around the alpha-carbon. Moreover, Vmax/Km values for demethylation
      are larger than for dealkylation, implying the reactions are under kinetic
      control. Comparison of the kinetic data with theoretical AM1 semi-empirical
      molecular orbital calculations suggests a mechanism involving formation of a
      carbon-centred radical. Use of an N-cyclopropylmethylbenzamide substrate to trap
      such a radical failed, presumably because oxygen rebound is faster than radical
      rearrangement. An N-cyclopropylamide substrate did not undergo metabolism of the
      cyclopropyl ring, consistent with carbon-centred radical, but not nitrogen
      radical cation, formation.

PMID- 8304973
TI  - Potentiation of adenylyl cyclase in human peripheral blood mononuclear cells by
      cell-activating stimuli.
AB  - The isoprenaline-induced production of cAMP in human peripheral blood mononuclear
      cells (PBMC) was potentiated significantly by incubating PBMC with isoprenaline
      in the presence of phytohaemagglutinin (PHA), Concanavalin A (Con A) or A23187.
      This potentiation, that proved to be dependent on the concentration of PHA, Con A
      or A23187, increased the maximal response but did not cause a change in the
      potency of isoprenaline. Potentiation could not be induced by the phorbol ester
      phorbol-myristate acetate, suggesting that protein kinase C-dependent pathways
      are not likely to be involved in potentiation of adenylyl cyclase. Potentiation
      could be inhibited by chelating extracellular Ca2+ with EGTA and also by N-(6
      aminohexyl)-5-chloro-1-naphthalenesulfonamine, an inhibitor of calmodulin.
      Potentiation could not be induced by preincubation of PBMC with PHA, suggesting
      that transient biochemical changes are involved. It was concluded from these
      results that potentiation in PBMC probably involves the activation of
      Ca2+/calmodulin-dependent adenylyl cyclase subtypes. Potentiation of the adenylyl
      cyclase activity could be an important physiological mechanism in vivo preventing
      cells from becoming "over stimulated".

PMID- 8304975
TI  - Oxidative activity of primaquine metabolites on rat erythrocytes in vitro and in
      vivo.
AB  - The oxidative activities of primaquine [6-methoxy-8-(4-amino-1
      methylbutylamino)quinoline] and its metabolites, the quinone-imine derivatives of
      5-hydroxyprimaquine [5-hydroxy-6-methoxy-8-(4-amino-1-methylbutylamino)quinoline]
      and 5-hydroxydemethylprimaquine [5-hydroxy-6-demethyl-8-(4-amino-1
      methylbutylamino)quinoline], 6-methoxy-8-amino quinoline and hydrogen peroxide,
      were studied on rat erythrocytes in vitro and in vivo. In both cases, the most
      effective metabolites in oxidizing hemoglobin and depleting non-protein
      sulfhydryl groups from erythrocytes were the quinone-imine derivatives of the
      ring-hydroxylated metabolites, 5-hydroxyprimaquine and 5-hydroxydemethyl
      primaquine. The latter quinone-imines were shown by light absorption spectroscopy
      and oxygen consumption studies to be able to oxidize purified rat hemoglobin to
      methemoglobin but to be unable to react directly with reduced glutathione. In
      agreement with these results, no radical adduct was detected by electron
      paramagnetic resonance spectroscopy in incubations of rat erythrocytes with the
      quinone-imines and the spin-trap 5,5-dimethyl-1-pyrroline-N-oxide; metabolite
      derived free radicals were detected instead. Taken together, the results suggest
      that 5-hydroxyprimaquine and 5-hydroxydemethylprimaquine are important
      metabolites in the expression of primaquine hemotoxicity, in contrast to 6
      methoxy-8-aminoquinoline. Additionally, the results indicate that hydrogen
      peroxide is the ultimate oxidant formed from the ring-hydroxylated metabolites by
      redox-cycling of the corresponding quinone-imine derivatives both in vitro and in
      vivo.

PMID- 8304974
TI  - Monoamine oxidase inhibition by novel antidepressant tetrindole.
AB  - The novel antidepressant tetrindole (2,3,3a,4,5,6-hexahydro-8-cyclohexyl-1H[3,2,1
      j,k] carbazole) was found to be a selective inhibitor of monoamine oxidase A (MAO
      A). In vitro it inhibited rat brain mitochondrial MAO A in a competitive manner
      with Ki value of 0.4 microM. A 60 min preincubation did not change the
      competitive mode of interaction between enzyme and tetrindole (Ki value was 0.27
      microM). The inhibition of rat brain mitochondrial MAO B was of mixed type with
      Ki value of 110 microM. Dilution or dialysis of mitochondrial suspension did not
      restore MAO A activity after inhibition by tetrindole both in vitro and in vivo,
      whereas inhibition of MAO B in vitro was completely reversible. Oral
      administration of tetrindole inhibited rat brain and liver mitochondrial MAO A by
      80% within 0.5-1 hr and the onset of recovery of enzyme activity became evident
      after 24 hr. A small inhibition of MAO B (-20-30%) was observed in isolated brain
      and liver mitochondria within 1-6 hr and enzyme activity had completely recovered
      after 16 hr. The data obtained indicate that antidepressant activity of
      tetrindole may be explained by selective inhibition of MAO A, however an apparent
      discrepancy between competitive manner of MAO A inhibition in vitro and poor
      recovery of enzyme activity in vivo does not allow us to decide whether
      tetrindole is a "tight-binding" reversible inhibitor or a selective irreversible
      inhibitor of MAO A.

PMID- 8304976
TI  - Influence of amsacrine (m-AMSA) on bulk and gene-specific DNA damage and c-myc
      expression in MCF-7 breast tumor cells.
AB  - In the MCF-7 human breast tumor cell line, the aminoacridine, m-AMSA, induces
      protein-associated DNA strand breaks consistent with inhibition of topoisomerase
      II. However, neither single-strand nor double-strand breaks in DNA, determined
      using conventional assays, show a consistent relationship with m-AMSA-induced
      inhibition of growth. In contrast, when DNA strand breaks are determined by
      alkaline unwinding under the high salt conditions of the alkaline
      unwinding/Southern blotting (AU/SB) assay, developed by our laboratories, damage
      to DNA corresponds closely with growth inhibition. The AU/SB assay, which is
      capable of assessing breaks within large-scale domains (upwards of 1 megabase)
      surrounding genes of interest, was further utilized to explore the capacity of m
      AMSA to induce damage within specific genomic regions that may regulate cell
      growth. Regions encompassing the transcriptionally active oncogenes, c-myc and c
      fos, were found to be more susceptible to m-AMSA-induced strand breaks than the
      region encompassing the non-transcribed alpha-satellite DNA or the genome as a
      whole (bulk DNA). These findings demonstrate that m-AMSA may produce more
      pronounced damage within specific genomic regions than in bulk DNA, m-AMSA also
      preferentially altered expression of the c-myc oncogene; at an m-AMSA
      concentration where growth was inhibited by between 70 and 80%, steady-state c
      myc mRNA levels declined to approximately 10-15% of control levels within 2-3 hr;
      furthermore, concentration-dependent reductions in c-myc expression appeared to
      coincide with growth inhibition. In addition, inhibition of [3H]thymidine
      incorporation after 2 hr directly paralleled inhibition of growth, suggesting an
      early effect at the level of DNA biosynthesis, possibly related to the down
      regulation of c-myc expression. It is proposed that specific lesions, e.g., in
      regions surrounding the c-myc gene, as well as generalized lesions in DNA may
      lead to growth inhibition mediated by down-regulation of the expression of select
      growth regulatory genes, such as c-myc.

PMID- 8304977
TI  - Heterogeneity of ouabain binding sites in Schistosoma mansoni. First evidence for
      the presence of two (Na+ + K+)-ATPase isoforms in platyhelminths.
AB  - Binding experiments with [3H]ouabain were performed to investigate the presence
      of (Na+ + K+)-ATPase (EC3.6.1.3) isoforms in adult male Schistosoma mansoni, the
      trematode responsible for human schistosomiasis. Non-linear regression analysis
      of equilibrium experiments performed with homogenates in a Mg-Pi medium indicated
      the presence of about 10% (Bmax = 223 +/- 67 fmol/mg protein) high-affinity sites
      (KD = 0.285 +/- 0.045 microM) and 90% (Bmax = 2117 +/- 348 fmol/mg protein) sites
      with a 20-fold lower affinity (KD = 4.9 +/- 1.28 microM). This was confirmed by
      their-exponential decay of [3H]ouabain dissociation. Furthermore, determination
      of association and dissociation rate constants indicated that the two classes of
      binding sites differed by their dissociation rate constants for ouabain (k-1 =
      0.0185 +/- 0.0019 min-1 and 0.0997 +/- 0.0528 min-1 for high- and low-affinity
      sites, respectively). Surprisingly, the association rate constant measured for
      ouabain binding to S. mansoni homogenate (0.038 microM-1.min-1) was lower (25- to
      80-fold) than the one usually observed for mammalian enzymes. This is the first
      direct evidence for the existence of (Na+ + K+)-ATPase isoforms in
      platyhelminths, invertebrates of great importance from the phylogenetic point of
      view.

PMID- 8304978
TI  - Increased expression and characterization of two distinct folate binding proteins
      in murine erythroleukemia cells.
AB  - We previously identified two membrane-bound folate binding proteins, FBP1 and
      FBP2, in murine L1210 leukemia cells. We now report on the development of two
      variant murine erythroleukemia cell lines that were used for direct comparison
      and biochemical characterization of the two murine folate binding proteins. Based
      on the results of northern analysis and the mobilities of affinity-labeled
      proteins on polyacrylamide gels, these cell lines exhibit specific up-regulated
      expression of FBP1 or FBP2. The affinities of the folate binding proteins for
      various (anti)folates were determined based upon the ability of the compounds to
      inhibiting of [3H]folic acid. The two proteins exhibited considerably different
      affinities and stereospecificities and, in general, FBP2 consistently bound each
      test compound with lesser affinity than FBP1. Both proteins displayed greatest
      affinity for folic acid, 5-methyltetrahydrofolate, and the antifolates CB3717 and
      5,10-dideazatetrahydrofolate (DDATHF). Conversely, the proteins exhibited poor
      affinity for the dihydrofolate reductase inhibitors methotrexate and aminopterin.
      For 5-formyltetrahydrofolate, FBP1 had high affinity for the (6S)
      diastereoisomer, whereas FBP2 showed preference for the non-physiologic (6R)
      diasterceoisomer. The binding properties of FBP1 and FBP2 overexpressed in these
      cell lines closely paralleled those of their respective human homologs. These
      lines provide a model system in which to examine the biochemical characteristics
      of the individual folate binding proteins without the potential problems
      associated with expression of proteins in dissimilar cell lines.

PMID- 8304979
TI  - Amplification of the effectiveness of acetylcholinesterase for detoxification of
      organophosphorus compounds by bis-quaternary oximes.
AB  - Pretreatment of rhesus monkeys with fetal bovine serum acetylcholinesterase (FBS
      AChE) provides complete protection against 5 LD50 of organophosphate (OP) without
      any signs of toxicity or performance decrements as measured by serial probe
      recognition tests or primate equilibrium platform performance (Maxwell et al.,
      Toxicol Appl Pharmacol 115: 44-49, 1992; Wolfe et al., Toxicol Appl Pharmacol
      117: 189-193, 1992). Although such use of enzyme as a single pretreatment drug
      for OP toxicity is sufficient to provide complete protection, a relatively large
      (stoichiometric) amount of enzyme was required in vivo to neutralize OP. To
      improve the efficacy of cholinesterases as pretreatment drugs, we have developed
      an approach in which the catalytic activity of OP-inhibited FBS AChE was rapidly
      and continuously restored, thus detoxifying the OP and minimizing enzyme aging by
      having sufficient amounts of appropriate oxime present. The efficacy of FBS AChE
      to detoxify several OPs was amplified by addition of bis-quaternary oximes,
      particularly 1-(2-hydroxyiminomethyl-1-pyridinium)-1-(4-carboxyaminopyridinium) 
      dimethyl ether hydrochloride (HI-6). When mice were pretreated with sufficient
      amounts of FBS AChE and HI-6 and challenged with repeated doses of O-isopropyl
      methylphosphonofluridate (sarin), the OP was continuously detoxified so long as
      the molar concentration of the sarin dose was less than the molar concentration
      of AChE in circulation. The in vitro experiments showed that the stoichiometry of
      sarin:FBS AChE was higher than 3200:1 and in vivo stoichiometry with mice was as
      high as 57:1. Addition of HI-6 to FBS AChE as a pretreatment drug amplified the
      efficacy of enzyme as a scavenger of nerve agents.

PMID- 8304980
TI  - Hypocholesterolemic properties of plant indoles. Inhibition of acyl
      CoA:cholesterol acyltransferase activity and reduction of serum LDL/VLDL
      cholesterol levels by glucobrassicin derivatives.
AB  - Studies were undertaken to investigate the effects of the plant compound indole-3
      carbinol (I3C) and its acid condensation products, which are generated in the
      stomach following ingestion of I3C, on cholesterol homeostasis in mice.
      Individual acid condensation products were synthesized and purified by HPLC. In
      vitro experiments revealed that several of the acid condensation products
      effectively inhibited the enzyme acyl-CoA:cholesterol acyltransferase (ACAT),
      which is responsible for the conversion of free cholesterol to the cholesteryl
      ester, at micromolar concentrations. Since the inhibition of ACAT in vivo should
      reduce serum cholesterol levels, I3C was administered to mice, and the effects on
      serum cholesterol levels were evaluated. Total serum cholesterol levels were
      elevated by 29% in mice provided a 3% cholesterol-supplemented diet, but this
      elevation was attenuated significantly (P < or = 0.05) by approximately 50% when
      I3C (100 mg/kg/day) was added to this diet. This effect of I3C was entirely on
      low density lipoprotein (LDL)/very low density lipoprotein (VLDL) cholesterol,
      which was lowered significantly (P < or = 0.05) by approximately 30%. In summary,
      I3C lowered serum LDL/VLDL cholesterol levels in mice, and this effect was likely
      mediated by the inhibition of ACAT by some of the acid condensation products of
      I3C. These results provide a possible mechanism by which I3C-rich vegetables
      lower serum cholesterol levels.

PMID- 8304981
TI  - 2'-Deoxy-2'-methylene derivatives of adenosine, guanosine, tubercidin, cytidine
      and uridine as inhibitors of L1210 cell growth in culture.
AB  - The 2'-deoxy-2'-methylene derivatives of adenosine (MdAdo), guanosine (MdGuo),
      tubercidin (MdTu), cytidine (MdCyd) and uridine (MdUrd) were synthesized as
      mechanism-based inhibitors directed at ribonucleotide reductase. It was shown
      that MdCyd 5'-diphosphate irreversibly inactivated ribonucleotide reductase from
      Escherichia coli (Baker et al., J Med Chem 34: 1879-1884, 1991). In studies
      reported here, MdAdo/EHNA, MdGuo and MdCyd inhibited L1210 cell growth with IC50
      values of 3.4, 10.6 and 1.4 microM, respectively. Since MdAdo is a substrate for
      adenosine deaminase, the presence of EHNA was required to give maximal growth
      inhibition. 8-Aminoguanosine was not required to maximize the cytotoxic effects
      of MdGuo. The 2'-deoxy-2'-methylene derivatives of tubercidin and uridine did not
      inhibit L1210 cell growth at concentrations as high as 50 microM (MdTu) or 100
      microM (MdUrd). L1210 cell lines resistant to hydroxyurea (directed at the non
      heme iron subunit of ribonucleotide reductase) or deoxyadenosine (directed at the
      effector binding subunit of ribonucleotide reductase) were not resistant to
      MdCyd. An L1210 cell line that was highly resistant to dGuo due to the loss of a
      relatively specific deoxyribonucleoside kinase (Cory et al., J Biol Chem 268: 405
      409, 1993) had a 6.6-fold increase in the IC50 value toward MdCyd, but showed
      only a 2-fold increase in resistance to MdGuo. Another L1210 cell line that was
      markedly deficient in adenosine kinase activity was highly resistant to MdAdo.
      Analysis by flow cytometry showed that MdCyd showed the transit of the cells
      through the G2/M phase of the cell cycle resulting in the buildup of the G2/M
      population. MdAdo, MdGuo and MdCyd inhibited the incorporation of [14C]cytidine
      into DNA without an effect on RNA synthesis or total cellular uptake of
      [14C]cytidine. The conversion of [14C]cytidine to deoxycytidine nucleotides was
      partially inhibited by MdGuo, but not by MdAdo or MdCyd. These data show that the
      2'-deoxy-2'-methylene derivatives of adenosine, guanosine and cytidine are
      activated via specific nucleoside kinases and that the modes of action of these
      compounds are not identical.

PMID- 8304982
TI  - Phorbol regulation of topoisomerases I and II in human leukemia cells. Studies in
      an additional cell pair sensitive or resistant to phorbol-induced
      differentiation.
AB  - We previously reported (Zwelling et al., Cancer Res 50: 7116-7122, 1990) that
      etoposide-induced DNA cleavage and mRNA coding for topoisomerase II are reduced
      in HL-60 cells induced to differentiate by phorbol ester. Reduction of etoposide
      induced cleavage and topoisomerase II message did not occur in the derived cell
      line 1E3 (which is resistant to phorbol-induced differentiation), implying that
      topoisomerase II activity may be related to the state of cell differentiation. We
      have extended these studies using a new phorbol sensitive/resistant cell pair, S
      (sensitive) and PET (phorbol ester tolerant). Phorbol ester exposure not only
      reduced etoposide-induced DNA cleavage and topoisomerase II mRNA in S cells but
      also decreased the amount of immunoreactive topoisomerase II enzyme in whole S
      cells. However, immunoreactive topoisomerase II extracted from the nuclei of
      phorbol-treated S cells was not reduced compared with that from the nuclei of
      untreated S cells. This suggests that topoisomerase II contained in nuclear
      extracts is not always representative of the total cellular enzyme. Dramatic
      decreases in the amount, activity, or gene expression of topoisomerase II were
      not observed after phorbol treatment of the resistant PET cells; this is
      consistent with the potential involvement of topoisomerase II in monocytoid
      differentiation. Levels of topoisomerase I enzyme and mRNA fell in both S and PET
      cells after phorbol treatment; therefore, the genes for topoisomerases I and II
      did not appear to be regulated coordinately.

PMID- 8304983
TI  - alpha-Fluoromethylhistidine-induced inhibition of brain histidine decarboxylase.
      Implications for the CO2-trapping enzymatic method.
AB  - The actions of S-alpha-fluoromethylhistidine (FMH), an irreversible inhibitor of
      the histamine biosynthetic enzyme histidine decarboxylase (HD), were studied on
      rat brain HD, as measured by a recently developed CO2-trapping enzymatic method.
      As expected, FMH induced a virtually complete inhibition of HD in the
      hypothalamus both in vivo and in vitro. In the frontal cortex, however, maximal
      doses of FMH did not maximally inhibit HD, suggesting the existence of an FMH
      resistant form of HD. Careful studies of the conditions under which the assays
      were performed (homogenate dilution, preincubation times, incubation times,
      temperatures), as well as experiments with inhibitors of other decarboxylases,
      were unable to provide an explanation for this. When comparable studies of the
      effects of FMH in these brain regions were performed by alternative methods for
      measuring HD activity, no evidence for the existence of an FMH-resistant form of
      HD could be found. Thus, even though the CO2-trapping method appears to be
      accurate for measuring HD activity in rat hypothalamic homogenates, the present
      results show that this method may not be specific when studying brain regions
      other than the hypothalamus.

PMID- 8304984
TI  - Modulation of human colonic T84 cell secretion by hydrogen peroxide.
AB  - Hydrogen peroxide (H2O2) is a reactive oxygen species that can be produced in the
      digestive tract by inflammatory cells or during reperfusion following ischemia.
      To evaluate a possible direct effect of H2O2 on epithelial secretory cells, well
      differentiated colonic T84 cells were grown to confluence on permeable membranes
      and studied in Ussing chambers. In this model, where the measured short-circuit
      current (Isc) reflects electrogenic secretion, we observed that H2O2 stimulated a
      concentration-dependent and transient secretory response: 5.5 mM H2O2 produced a
      peak Isc of 12.4 microA/cm2 after 4 min, 2.2 mM H2O2 a peak Isc of 7.9 microA/cm2
      after 4 min, and 1.1 mM H2O2 a peak Isc of 5.5 microA/cm2 after 16 min (N = 5).
      When 97 experiments using 5.5 mM H2O2 were reviewed, the mean peak Isc response
      was 8.9 +/- 0.5 microA/cm2. A similar secretory response was elicited whether
      H2O2 was added to the serosal, to the mucosal, or simultaneously to both sides of
      the T84 cell monolayer. This secretory response reflected transcellular chloride
      secretion because it was inhibited by the depletion of chloride in the medium and
      by the suppression of the Na+,K+,2Cl- co-transporter activity necessary for the
      chloride gradient driving chloride secretion. When T84 cell monolayer resistance
      was studied, 5.5 mM H2O2 produced a transient decrease in resistance, reflecting
      transcellular chloride secretion, and a gradual decline in resistance (75% of the
      initial value after 55 min). The secretory response to H2O2 was increased 2-fold
      in T84 cells maximally stimulated with 10 nM vasoactive intestinal peptide (VIP),
      a neuropeptide which acts via cAMP, demonstrating synergism between the two
      agents. In contrast, the secretory responses produced by H2O2 and carbachol,
      which acts through the Ca2+ pathway, were additive. A late inhibitory effect of
      H2O2 was also observed: in cells previously treated with 5.5 mM H2O2, the
      subsequent secretory responses to either VIP or carbachol were partially
      inhibited. These secretory effects were specific for the oxidant properties of
      H2O2 because they were inhibited by 450 U/mL catalase and by 5 mM dithiothreitol,
      but were unaffected by 50 microM deferoxamine B or Fe3+. H2O2 may be a potential
      modulator of intestinal or colonic secretion in certain pathologic conditions
      such as inflammation or ischemia-reperfusion.

PMID- 8304985
TI  - Phospholipase C and phospholipase D are independently activated in rat
      hippocampal slices.
AB  - In order to investigate a possible G-protein-mediated activation of phospholipase
      D (PLD) and its relationship to the activation of phosphoinositide-specific
      phospholipase C (PI-PLC), we measured the effects of aluminium fluoride and
      carbachol on choline release, the PLD-specific transphosphatidylation reaction
      (generation of phosphatidylpropanol) and the formation of inositol phosphates in
      rat hippocampal slices. Aluminium fluoride markedly enhanced the formation of
      choline and phosphatidylpropanol but failed to increase the formation of inositol
      phosphates. In contrast, the muscarinic agonist carbachol strongly stimulated PI
      PLC but failed to activate PLD. We conclude that PLD in hippocampal slices is
      activated by a G-protein independently of phosphoinositide hydrolysis.

PMID- 8304986
TI  - Analysis of free fatty acid effect on methotrexate binding to albumin.
AB  - The binding of methotrexate to human serum albumin and the inhibitory effect of
      serum free fatty acids (FFA) have been studied by equilibrium dialysis with
      radiolabeled methotrexate. Methotrexate was bound to albumin via a single site
      (1.03 +/- 0.02) with a low affinity (1350 +/- 60 M-1). The effect of FFA on
      binding by albumin of methotrexate was analysed according to the classical
      inhibition models with computation of the free inhibitor concentration and was
      ascribed to an uncompetitive type of inhibition. These results were in agreement
      with the observed serum binding of methotrexate (45-50%) and allowed the
      simulation of the effect of various concentrations of FFA on methotrexate albumin
      binding in human serum.

PMID- 8304987
TI  - Antimalarial activity in vitro of the glyoxalase I inhibitor diester, S-p
      bromobenzylglutathione diethyl ester.
AB  - S-p-Bromobenzylglutathione diethyl ester induced toxicity in the malarial
      parasite Plasmodium falciparum in infected human red blood cells in culture. The
      median inhibitory concentration, IC50, was 4.77 +/- 0.12 microM (N = 10) for
      incorporation of [3H]hypoxanthine in nucleotide synthesis and 5.20 +/- 0.1 microM
      (N = 10) for incorporation of [14C]isoleucine into protein. The prospective
      mechanism of action is inhibition of glyoxalase I by the de-esterified
      metabolite, S-p-bromobenzylglutathione, and accumulation of the cytotoxic
      substrate methylglyoxal.

PMID- 8304988
TI  - Inhibition of protein kinase C by melittin: antagonism of binding interactions
      between melittin and the catalytic domain by active-site binding of MgATP.
AB  - Melittin inhibits the lipid cofactor-independent activity of protein kinase C
      (PKC) by directly binding to the catalytic domain in a MgATP-sensitive manner.
      The catalytic domains of certain PKC isozymes have a consensus sequence for a
      second nucleotide binding site outside their active site regions. In this report,
      we show that PKC isozymes containing the second nucleotide binding site motif
      (alpha, beta) and an isozyme lacking the motif (epsilon) all have MgATP-sensitive
      binding interactions with melittin. Our results support a mechanism of PKC
      inhibition by melittin in which active-site binding of MgATP antagonizes binding
      interactions between PKC and melittin.

PMID- 8304989
TI  - Are schizophrenia and affective disorder related? preliminary data from a family
      study.
AB  - OBJECTIVE: Most investigators presume that schizophrenia and affective disorder
      are separate diseases. Others have proposed alternatives to this Kraepelinian
      view. These alternatives were addressed by preliminary analyses of data from a
      family study of psychopathology. METHOD: The authors identified 1,895 first
      degree relatives of 166 patients with DSM-III schizophrenia, 71 patients with
      affective disorder, and 85 medical comparison probands; 949 relatives were
      blindly diagnosed. RESULTS: The risks for schizophrenia and affective disorder
      (unipolar melancholia and bipolar disorder combined) were significantly higher in
      the relatives of the schizophrenic probands and the relatives of the probands
      with affective disorder than in the relatives of the comparison probands. The
      morbid risk for nonmelancholic depressions was not significantly higher. Among
      the relatives of the schizophrenic probands, the risk for affective disorder was
      highest among the relatives of the patients with "core" schizophrenia, who were
      younger at illness onset, had chronic illness, had severe emotional blunting, and
      showed few affective features. CONCLUSIONS: Despite limitations, these
      preliminary analyses, consistent with other studies, suggest some familial
      relationship between schizophrenia and severe forms of affective disorder.

PMID- 8304990
TI  - Application of high-tech three-dimensional imaging and computer-generated models
      in complex facial reconstructions with vascularized bone grafts.
AB  - We present a series of six patients with eight flaps in whom computer-generated
      models were used for fabrication of vascularized bone grafts in complex facial
      restorations. Preoperative CT data, digitalized on tape, were converted by the
      CEMAX (Santa Clara, Calif.) 1500 Integrated Hardware and Software System to a
      three-dimensional visualization of the bone and soft-tissue deficiencies. These
      data were transmitted by direct computer link to a CNC milling machine that
      produced full-size slices "stacked" into a three-dimensional template. The
      acrylic replica aided selection of appropriate donor sites and intraoperative
      "carving" of bone transfers. Reconstructions included three zygomas, two
      maxillae, two mandibles, and one frontal bone. Donor sites were iliac crest,
      scapula, and outer calvarium. Four were free flaps and four island pedicle flaps.
      All healed without infection. Bone resorption was less than 10 percent. One flap
      was lost to thrombosis. Other complications included a transient facial palsy in
      one patient and temporary radial palsy from shoulder traction in another.
      Computer-generated templates for vascularized grafts are expensive and thus are
      not indicated or necessary in every patient. The advantages, however, are
      several. Custom models facilitate preoperative planning, with less guesswork of
      size, contour, and orientation of the graft, which is especially desirable with
      vascularized grafts, since the position of the pedicle is critical. Anesthesia
      time is decreased. Grafts can be fitted exactly, without reshaping and
      "nibbling." Nuances of depth and tapering are directly carved into the bone. By
      merging high-tech imaging and microsurgery, the best chance of optimal results
      can be achieved.

PMID- 8304991
TI  - Programmed instruction: cancer chemotherapy.  Basic principles.

PMID- 8304992
TI  - "Self-referral"--what's at stake?

PMID- 8304993
TI  - Migration of a Kirschner wire from the sternum to the right ventricle. A case
      report.

PMID- 8304994
TI  - Ventilatory support in asthma.
AB  - Mechanical ventilation in acute asthma is associated with significant morbidity
      and mortality, and maximal medical therapy should prevent it being used
      inappropriately. We review current standards of medical therapy in acute asthma,
      the indications for mechanical ventilation and its management.

PMID- 8304995
TI  - Unusual presentation of a chondromyxoid fibroma of the mandible. Report of a case
      and review of the literature.
AB  - Chondromyxoid fibromas are uncommon central bone tumors that are most often found
      at the proximal metaphyses of long bones. Chrondromyxoid fibromas of the jaws are
      very rare with only 18 reported cases in the literature. This article reports on
      a recurrent chondromyxoid fibromas of the mandible in a 10-year-old boy. In
      addition, a literature review of the clinical and histologic features, as well as
      the diagnostic pitfalls and recommended modalities of treatment are presented.

PMID- 8304996
TI  - Carotid endarterectomy with transcranial Doppler and electroencephalographic
      monitoring. A prospective study in 130 operations.
AB  - BACKGROUND AND PURPOSE: We report the results of combined recording of
      hemodynamic and thromboembolic phenomena during carotid endarterectomy by means
      of computerized electroencephalography as well as transcranial Doppler
      ultrasonography. The study focuses on the additional value of transcranial
      Doppler to detect ischemia during surgery. METHODS: Combined monitoring was
      performed in 130 consecutive operations, using standard anesthesiological,
      surgical, and neurophysiological procedures. RESULTS: A reduction of > or = 70%
      of blood flow velocities in the middle cerebral artery during cross-clamping was
      measured in 16 patients. In seven of these cases there were no severe
      electroencephalographic changes and a shunt was not used, but one of the patients
      developed a subcortical infarct with slight disability. In 55 patients, 75
      episodes of embolization were detected by transcranial Doppler. In one of these,
      with massive embolization after release of the clamp, an intraoperative stroke
      occurred without changes on cranial computerized tomography or neurological
      disability on follow-up. In the other 54 patients, intraoperative embolization
      did not cause clinical or neuroradiological symptoms. Electroencephalographic
      changes occurred in only two of the 75 episodes. In addition to the two
      nondisabling strokes during surgery (1.5%), six strokes occurred within 5 days of
      operation, including one hemorrhage. There was no significant relation between
      contralateral carotid occlusion and stroke (p = 0.6). CONCLUSIONS: During carotid
      endarterectomy, transcranial Doppler immediately provides information about
      thromboembolism and hemodynamic changes that are not detected by
      electroencephalography alone. Acoustic feedback from the transcranial Doppler
      monitoring unit has a direct influence on the surgical technique. Transcranial
      Doppler ultrasound may be a useful tool in the study and prevention of
      intraoperative stroke.

PMID- 8304997
TI  - Oncology nurses' attitudes regarding voluntary, physician-assisted dying for
      competent, terminally ill patients.
AB  - Euthanasia and "voluntary dying" are among the most controversial issues involved
      in cancer care. The purpose of this descriptive study was to explore oncology
      nurses' attitudes about physician-assisted death (PAD) for competent, terminally
      ill adults who request this assistance. Questionnaires were sent to 2,000
      randomly selected members of the Oncology Nursing Society. The questionnaires
      included demographic questions, four vignettes describing patient care situations
      and possible responses based on beliefs about PAD, and questions that explored
      awareness of organizations and legislation that promote legalization of PAD. The
      response rate was 61% (1,210). Findings indicate that oncology nurses hold
      diverse views regarding the acceptability of PAD. Although many nurses favored
      PAD, they also expressed a reluctance to administer the medication that would
      cause death. Given that PAD is an ethical and legal issue in the United States
      for terminally ill patients, nurses are encouraged to become informed about the
      concept of PAD and be prepared to actively respond to the policy-making
      ramifications of the assisted-death movement.

PMID- 8304998
TI  - The geographical distribution of psychiatrists in Canada: unmet needs and
      remedial strategies.
AB  - Many efforts are underway to rationalize the process of manpower planning in
      psychiatry. A wide variation in the geographic distribution of psychiatrists
      remains. A multidimensional assessment of the needs of a population is
      recommended, based on the epidemiology of mental disorders, professional and
      institutional needs, consumer estimates, and the requirements of subgroups.
      Counting the number of vacant positions for psychiatrists can be misleading.
      Professional norms for the optimal access of a population to psychiatric services
      and standards for the quantity and/or quality of services provided need to be
      developed. Potential outcome measures are suggested, along with a three-tiered
      system of estimating geographic needs. Deterrent factors to an optimal geographic
      distribution of most professionals are reviewed, along with factors specific to
      our residency training programs. In the short term, the benefits and limitations
      of recruiting foreign-trained psychiatrists are compared with those of recruiting
      Canadian specialists. Complementary long term strategies include the provision of
      financial incentives, optimal working conditions, relevant training and
      maintenance of competence issues, and community support.

PMID- 8304999
TI  - A geriatrician's guide to enteral feeding.

PMID- 8305000
TI  - Lead poisoning among low-income children in Orange County, California. A need for
      regionally differentiated policy.
AB  - OBJECTIVE: To estimate the prevalence of elevated lead levels among children in
      Orange County, California, and to evaluate the appropriateness of a universal
      pediatric blood lead screening policy in this community. DESIGN: Venous blood
      lead testing was conducted and results were analyzed according to seven blood
      lead strata ranging from less than 0.50 mumol/L (10 micrograms/dL) to 3.35
      mumol/L (70 micrograms/dL) or higher. A cost analysis of the lead-testing program
      in Orange County was conducted. SETTING: Children meeting poverty eligibility
      criteria and attending the Child Health and Disability Prevention Program, the
      state's implementation of the federal Early and Periodic Screening, Diagnosis and
      Treatment (EPSDT) services program. PARTICIPANTS: A total of 5115 Orange County
      children between 12 and 72 months of age using EPSDT services from March through
      December 1992. MAIN OUTCOME MEASURES: Blood lead levels and associated costs of
      the testing program stratified by level of blood lead elevation. RESULTS: Blood
      lead levels of 0.50 mumol/L (10 micrograms/dL) or higher were found in 371
      children (7.25%; 95% confidence interval, 6.66% to 7.85%), but only six children
      (0.12%; 95% confidence interval, 0.04% to 0.20%) had elevations greater than 1.20
      mumol/L (25 micrograms/dL). Five children (83.3%) had histories of lead
      consumption unrelated to ingestion of lead-containing paint but related to the
      use of lead-containing folk remedies and cooking utensils. Costs for detection of
      children with blood levels elevated to 0.50 mumol/L (10 micrograms/dL) or higher
      was $310 per child and for levels of 1.20 mumol/L (25 micrograms/dL) or higher
      was $19,139 per child. CONCLUSIONS: These data suggest that lead poisoning is not
      a major public health problem among Orange County children and detection of
      infrequent cases would involve a high cost per child. In jurisdictions with newer
      housing, initial screening for a history of possible lead exposure alone may
      offer reasonable efficacy that is cost-effective. The scope of lead-testing
      programs should be determined according to local needs and conditions.

PMID- 8305001
TI  - Cholesterol reduction and the risk for stroke in men. A meta-analysis of
      randomized, controlled trials.
AB  - OBJECTIVE: Reducing serum cholesterol lowers the risk for ischemic heart disease,
      but its effects on other vascular diseases are unknown. Published trials were
      reviewed to determine the effect of cholesterol-lowering interventions on fatal
      and nonfatal stroke. DESIGN: Meta-analysis of randomized, controlled trials. DATA
      IDENTIFICATION: A literature search of English-language studies examining the
      effect of modified diets or medications on cardiovascular end points from 1965 to
      1992 using MEDLINE and a review of references of five quantitative overviews of
      cholesterol reduction and coronary disease. DATA ANALYSIS: Thirteen studies met
      three eligibility criteria: patients randomized to intervention or control; fatal
      or nonfatal stroke reported separately; and end points assessed without knowledge
      of treatment status. Heterogeneity among studies and overall effects of treatment
      on fatal and nonfatal stroke were estimated using the Mantel-Haenszel-Peto method
      to combine independent study results. The influence of various study designs and
      interventions was explored using subgroup comparisons. RESULTS: For fatal stroke,
      the overall odds ratio associated with cholesterol-lowering interventions in 13
      trials was 1.32 (95% Cl, 0.94 to 1.86), and the odds ratio for the 10 single
      intervention trials was 1.34 (Cl, 0.91 to 1.96). Among eight trials reporting
      nonfatal events, the summary odds ratio for nonfatal stroke for treated
      participants compared with controls was 0.88 (Cl, 0.70 to 1.11), and the odds
      ratio for total strokes was 0.98 (Cl, 0.80 to 1.19). Among three trials using
      clofibrate, treatment significantly increased the risk for fatal stroke (odds
      ratio, 2.64; Cl, 1.42 to 4.92) but not for nonfatal stroke (odds ratio, 0.87; Cl,
      0.61 to 1.26). Regression analysis showed no statistical association between the
      magnitude of cholesterol reduction and the risk for fatal stroke. CONCLUSIONS:
      Lowering serum cholesterol through modified diets or medications does not reduce
      stroke mortality or morbidity in middle-aged men. Clofibrate appears to increase
      the risk for fatal strokes, but the mechanism for this effect is unknown.

PMID- 8305002
TI  - The efficacy of oral vitamin K1: implications for future prophylaxis to prevent
      haemorrhagic disease of the newborn.

PMID- 8305003
TI  - Pneumothorax during laparoscopic dissection of the diaphragmatic hiatus.

PMID- 8305004
TI  - Women in clinical trials of new drugs. A change in Food and Drug Administration
      policy. The Working Group on Women in Clinical Trials.

PMID- 8305005
TI  - What is misconduct in science?

PMID- 8305006
TI  - Should paid organ donation be banned in India? To buy or let die!

PMID- 8305007
TI  - Endoscopic sympathectomy.

PMID- 8305008
TI  - Toxic terror; phantom risks.

PMID- 8305009
TI  - Failure to report drivers' medical problems could have serious legal consequences
      for MDs.

PMID- 8305010
TI  - Osteoarthritis: how to diagnose and treat the painful joint.
AB  - Osteoarthritis (OA) is the most common form of arthritis in older patients,
      causing pain that can significantly reduce function and quality of life. OA is
      classified as either primary or secondary disease, depending on the underlying
      etiology. Causes of secondary OA include trauma, other joint disease, and
      metabolic conditions. Diagnosis is based on patient history, physical
      examination, and radiographic findings. The mainstay of treatment is the use of
      nonsteroidal anti-inflammatory agents; NSAIDs that can be given once or twice
      daily increase patient compliance. Other therapeutic measures include exercise
      programs and--in patients with severe pain and limited function--surgical
      intervention.

PMID- 8305011
TI  - 'Do not resuscitate' orders and end-of-life care planning.

PMID- 8305012
TI  - Former New Zealand health minister offers blunt warning to Canadian doctors,
      politicians.

PMID- 8305013
TI  - Treatment of postherpetic neuralgia with topical piroxicam gel.

PMID- 8305014
TI  - Age, sex, and temporary resident originated prescribing units (ASTRO-PUs): new
      weightings for analysing prescribing of general practices in England.
AB  - OBJECTIVE: To derive demographic weightings to replace the existing system of
      prescribing units used in analysing prescribing by general practitioners in
      England. DESIGN: The prescribing data for one year from a sample of 90 practices
      in 80 family health service authority areas were used to calculate the relative
      frequency with which items were prescribed, for each sex, in nine age bands and
      for temporary residents. Data on the variation in cost per item by age and sex
      then allowed estimates to be made of the relative costs for these groups. Integer
      values for both the item based and cost based weightings were obtained by
      conversion to optimal integer scales. MAIN OUTCOME MEASURES: Item based and cost
      based weightings for each of the 18 age-sex groups and for temporary residents.
      The cost based weightings were considered more appropriate to the context in
      which the new system was to be used. RESULTS: Prescribing costs increased
      noticeably, for both sexes, in the middle years (ages 35-64). Compared with the
      existing system, the cost based weightings (ASTRO-PUs) gave greater weight to
      patients aged 45 and over, especially those in the 55-64 age band, at the expense
      of younger patients. Children under 5 received twice as many items as those aged
      5-14, but the inexpensiveness of their drugs made the cost based weightings of
      the two groups equal. Similarly, women were generally given more items than men,
      but at a lower average cost per item, which reduced differences between the sexes
      in the cost based weightings. Costs for patients aged 75 and over, compared with
      those aged 65-74, were higher only for women. CONCLUSIONS: The cost based
      weightings proposed are believed to reflect the present distribution of
      prescribing costs, in relation to age and sex, in English general practice. They
      are intended for use in analyses at practice level.

PMID- 8305016
TI  - Transmission of HIV in prison. Different aims, different strategies.

PMID- 8305015
TI  - Should purchasers pay for psychotherapy?

PMID- 8305017
TI  - On guns and violence.

PMID- 8305019
TI  - Osteitis pubis.
AB  - BACKGROUND: A 55-year-old woman was seen for pubic symphysis tenderness that
      started 3 weeks after bladder suspension surgery for urinary incontinence. A
      diagnosis of osteitis pubis was made based on the results of the physical,
      radiographic, and laboratory examinations. The paucity of information on this
      topic in primary care textbooks prompted a literature review of the subject.
      METHODS: A computer-assisted literature search of the MEDLINE files from 1966 to
      the present was performed using the terms "osteitis," "osteomyelitis," and "pubic
      symphysis." Older documents and papers of related interest were obtained by cross
      reference of the bibliographies of the articles generated by the search. RESULTS
      AND CONCLUSIONS: Osteitis pubis is an infrequent complication of pelvic surgery,
      parturition, or athletic activities. The diagnosis is made on the basis of the
      typical findings of pubic tenderness and pain on hip abduction that occurs a few
      weeks following the inciting event. Initial treatment consists of rest, physical
      therapy, and oral nonsteroidal or glucocorticoid anti-inflammatory medications.
      The use of intra-articular glucocorticoid injections is controversial. Surgery is
      rarely indicated and should be reserved for patients who have severe pain or
      pubic instability that has not responded to conservative therapy.

PMID- 8305018
TI  - Long-term eradication of Chlamydia trachomatis genital infection after
      antimicrobial therapy. Evidence against persistent infection.
AB  - OBJECTIVE: To determine whether Chlamydia trachomatis urogenital infections
      persist or relapse after antimicrobial therapy by serial measurement of
      chlamydial-specific DNA using the polymerase chain reaction (PCR), cell cultures,
      and serological studies. DESIGN: Prospective evaluation of an inception cohort.
      SETTING: University student health clinic. PARTICIPANTS: Twenty women with
      culture-proven and PCR-proven C trachomatis urogenital infections. MEASUREMENTS:
      Incidence of persistent infection as determined by PCR, culture, and serial
      measurement of local and systemic antibody to C trachomatis for 5 months after
      doxycycline therapy. RESULTS: Prior to therapy, C trachomatis was isolated in
      cell culture from the cervix in 19 of 20 women, from the urethra in 13 women, and
      from the rectum in 13 women. All culture-positive specimens were also PCR
      positive. Immediately after completion of antimicrobial therapy, all women had
      negative cell cultures for chlamydia. Ten of 20 culture-negative cervical
      specimens and two culture-negative urethral specimens had chlamydial DNA present
      immediately after treatment. In addition, three women had detectable DNA from
      cervical specimens 1 week after treatment. The presence of cervicitis (P = .01),
      high inclusion counts (P = .004), and serological evidence of recent infection (P
      = .0004) were each significantly associated with PCR positivity after treatment.
      All 384 subsequent cervical, rectal, and urethral specimens collected over 5
      months were negative by both PCR and culture with the exception of one woman who
      was reinfected. Serum immunoglobulin M (IgM) titers, geometric mean serum
      immunoglobulin G (IgG) titers, and prevalence of local antibody to chlamydia
      progressively declined after treatment. CONCLUSIONS: Standard antimicrobial
      therapy is effective in the long-term microbiologic eradication of uncomplicated
      C trachomatis urogenital infections. The presence of chlamydial DNA after
      antimicrobial therapy is of short duration and reflects excretion of nonviable
      organisms rather than persistent infection.

PMID- 8305020
TI  - C-fms expression in B-cells and response to M-CSF.

PMID- 8305021
TI  - Fibronectin: a predictor of preterm delivery?

PMID- 8305022
TI  - New Zealand and Canadian health care systems.

PMID- 8305023
TI  - Male and female circumcision in Canada.

PMID- 8305024
TI  - Laser surgery of the larynx: the cause for caution.

PMID- 8305025
TI  - Treating cocaine abusers.

PMID- 8305026
TI  - Comments on brucellosis testing.

PMID- 8305027
TI  - Supports approval of bovine somatotropin.

PMID- 8305028
TI  - Uncertain on the effects of tapering.

PMID- 8305029
TI  - Reply to "Question the experts".

PMID- 8305030
TI  - Shouldering the burden.

PMID- 8305031
TI  - Correction of biliary atresia and jejunal atresia in an infant.

PMID- 8305032
TI  - Peribulbar anesthesia.

PMID- 8305033
TI  - Planned Parenthood v Casey.

PMID- 8305034
TI  - Women's health.

PMID- 8305035
TI  - Carotid microendarterectomy.

PMID- 8305036
TI  - Ocular injury from amniocentesis.

PMID- 8305037
TI  - Vascularized bone grafts for facial reconstruction.

PMID- 8305038
TI  - CO2 chemoreception in the pulmonate snail, Helix aspersa.
AB  - We have studied the response of the pneumostome to CO2, O2 and combined CO2 and
      O2 in intact snails. We found that pneumostomal opening increases in response to
      both hypercapnia and mild hypoxia. We determined which neural structures were
      essential for the pneumostomal response to CO2 by eliminating parts of the
      nervous system: the subesophageal ganglia and an intact anal nerve were necessary
      and sufficient elements for the CO2 response. Within the subesophageal ganglia,
      we identified a discrete region on the medial margin of the visceral ganglion
      that was capable of increasing pneumostomal area when focally stimulated with 6%
      CO2. Ion substitution experiments indicated that pneumostomal responses to
      hypercapnia were not mediated by the pneumostomal motor neurons themselves, but
      rather by interneurons connected polysynaptically to the motor neurons
      controlling pneumostomal function. In conclusion, intact H. aspersa have a
      ventilatory response to CO2, and this response is mediated by CO2 sensitive cells
      located in a small area of the central nervous system.

PMID- 8305039
TI  - Environmental hazards: real or exaggerated?

PMID- 8305040
TI  - Serum therapy of a paretic syndrome of ostriches.

PMID- 8305041
TI  - Osteopathic manipulation and tension-type headaches.

PMID- 8305042
TI  - Re: "Magnetic fields of video display terminals and spontaneous abortion".

PMID- 8305043
TI  - Neurobiology of fetal breathing.

PMID- 8305044
TI  - The dangers of legalizing physician-assisted suicide.

PMID- 8305045
TI  - The valid assessment of personality disorders.

PMID- 8305046
TI  - Treatment of necrotizing pancreatitis.

PMID- 8305047
TI  - Inhibition of diamine oxidase is a risk in specific immunotherapy.

PMID- 8305048
TI  - The effect of low dose aspirin on bleeding times.

PMID- 8305049
TI  - Gastrointestinal bleeding after administration of ketorolac.

PMID- 8305050
TI  - Referencing publication of findings affecting pediatric cardiac massage.

PMID- 8305051
TI  - Re: Applications of the posterior thigh flap.

PMID- 8305052
TI  - Preoperative evaluation of patients for liver resection: appropriate CT imaging.

PMID- 8305053
TI  - Current expectations in cardiomyoplasty.

PMID- 8305054
TI  - Device-supported myocardial revascularization.

PMID- 8305055
TI  - p53 protein expression in cutaneous T cell lymphoma.

PMID- 8305056
TI  - Role of accessory spleens in human immunodeficiency virus-related immune
      thrombocytopenic purpura.

PMID- 8305057
TI  - Endoscopic sympathectomy.

PMID- 8305058
TI  - Pneumothorax during laparoscopic dissection of the diaphragmatic hiatus.

PMID- 8305059
TI  - Mandatory bicycle helmets?

PMID- 8305060
TI  - A patient with 21-hydroxylase deficiency who exhibited only maternal major
      histocompatibility complex (MHC) antigens.

PMID- 8305061
TI  - Palsy of the deep peroneal nerve after proximal tibial osteotomy. An anatomical
      study.

PMID- 8305062
TI  - A response to Aviel Goodman's "Sexual addiction: designation and treatment".

PMID- 8305063
TI  - Acute liver failure.

PMID- 8305064
TI  - Irritable bowel syndrome.

PMID- 8305065
TI  - Giant cell containing fibrous lesion of the sacrum.

PMID- 8305066
TI  - Leaking gel implants.

PMID- 8305067
TI  - Bone-graft reconstruction of the monkey orbital floor.

PMID- 8305068
TI  - Unknown radioligand specific activity.

PMID- 8305069
TI  - Comment on bonding systems.

PMID- 8305070
TI  - Nonsteroidal anti-inflammatory drugs and gastrointestinal injury in children.

PMID- 8305071
TI  - Dysutility of screening chest roentgenograms for lung cancer: the Ulysses
      syndrome.

PMID- 8305072
TI  - Xanthogranulomatous pyelonephritis and amyloidosis.

PMID- 8305073
TI  - Assessment of elderly people in hospital. Assessment scales unevaluated.

PMID- 8305074
TI  - Activated charcoal for chloroquine poisoning.

PMID- 8305075
TI  - General practice fundholding: observations on prescribing patterns and costs
      using the defined daily dose method.
AB  - OBJECTIVE: To compare prescribing patterns between a group of fundholding
      practices and a group of non-fundholding practices in north east Scotland using a
      method which provides more accurate statements about volumes prescribed than
      standard NHS statistics. DESIGN: The pharmacy practice division of the National
      Health Service in Scotland provided data for selected British National Formulary
      sections over two years. Each prescription issued was converted using the World
      Health Organisation "defined daily dose" mechanism. SETTING: Six fundholding
      groups (nine practices) in Grampian and Tayside regions and six non-fundholding
      practices in Grampian. RESULTS: During the past two years both fundholding and
      control practices reduced the volume of their prescribing for the classes of drug
      analysed. The unit costs of drugs in some classes, however, rose substantially,
      contributing to higher costs per patient. The unit costs rose more in the control
      practices (24%) than in the fundholding practices (11% in Tayside, 16% in
      Grampian). CONCLUSION: The use of defined daily doses helped identify cost and
      volume trends in specific areas of prescribing in fundholding and control
      practices. The basis on which funds are set needs improving, and defined daily
      doses may prove useful for setting volume targets within drug classes for all
      practices, whether fundholding or not.

PMID- 8305076
TI  - Drug-induced renal insufficiency.

PMID- 8305077
TI  - HeLa cross-contamination of a leukemia cell line.

PMID- 8305078
TI  - A cyclic GMP-stimulated cyclic nucleotide phosphodiesterase gene is highly
      expressed in the limbic system of the rat brain.
AB  - Cyclic AMP and cyclic GMP serve as second messengers in a variety of neural
      cells, modulating their metabolic and electrical activity. The cyclic GMP
      stimulated cyclic nucleotide phosphodiesterase, an enzyme whose hydrolytic
      activity is allosterically regulated by cyclic GMP in peripheral tissues, could
      play an important role in the regulation of cyclic nucleotide levels in the
      brain. To study the presence and distribution of cyclic GMP-stimulated
      phosphodiesterase in the rat brain, we cloned a portion of rat liver cyclic GMP
      stimulated phosphodiesterase complementary DNA by polymerase chain reaction,
      using degenerate phosphodiesterase-specific oligonucleotide primers. Northern
      blot analysis of rat tissues reveals abundant expression of cyclic GMP-stimulated
      phosphodiesterase messenger RNA in the brain. Northern blot analysis of brain
      subregions shows especially strong expression in hippocampus and cortex, modest
      expression in the remainder of the forebrain and in the midbrain, and little
      expression in cerebellum and hindbrain. In situ hybridization studies with cyclic
      GMP-stimulated phosphodiesterase riboprobes confirm these northern blot results,
      and delineate cell groups with high levels of expression. Medial habenular
      nucleus is intensely labeled, as is hippocampus in the vicinity of pyramidal and
      granule cell bodies in areas CA1, CA2, CA3, and dentate gyrus. Other elements of
      the limbic system also contain cyclic GMP-stimulated phosphodiesterase messenger
      RNA, including olfactory and entorhinal cortices, subiculum, and amygdala.
      Additional cortical regions show more diffuse expression of cyclic GMP-stimulated
      phosphodiesterase messenger RNA, as do the basal ganglia. Cerebellum, thalamus,
      and hypothalamus do not show appreciable specific labeling. These studies
      demonstrate the presence of cyclic GMP-stimulated phosphodiesterase messenger RNA
      in specific regions of the rat brain, and suggest that the cyclic GMP-stimulated
      phosphodiesterase might modulate neuronal activity by regulating intracellular
      cyclic AMP levels in response to changes in intracellular cyclic GMP levels.

PMID- 8305079
TI  - Serological correlates of susceptibility to pertussis.

PMID- 8305080
TI  - This wasn't euthanasia.

PMID- 8305081
TI  - Adult criteria for obstructive apnea do not identify children with serious
      obstruction.

PMID- 8305082
TI  - Does tumor hypoxia influence local control of carcinoma of the cervix?

PMID- 8305083
TI  - [Reconsideration of the use of episiotomy in primiparas].

PMID- 8305084
TI  - Thymectomy and severe combined immune-deficient bone marrow transplantation
      eradicates natural antibody of mice to human blood cells.

PMID- 8305085
TI  - Accelerated acute rejection of an A2 renal allograft in an O recipient:
      association with an increase in anti-A2 antibodies.

PMID- 8305087
TI  - Information processing under anaesthesia.

PMID- 8305086
TI  - Inflammatory polyneuropathy after heart transplantation. Its association with
      antibodies to asialo-GM1 and sulfatide.

PMID- 8305088
TI  - Sequence-tagged microsatellite sites as markers in chicken reference and resource
      populations.
AB  - Two chicken genomic libraries were screened for the presence of poly(TG/AC)
      microsatellite tracts. The number of positive clones was low, confirming the low
      frequency of such microsatellites in the chicken genome relative to mammalian
      genomes. Polymorphism of 29 microsatellite tracts, comprising 11 from the library
      screening and 18 obtained from GenBank, was examined in the East Lansing and
      Compton reference families, in a resource population formed by a cross between a
      single White Rock broiler and inbred Leghorn females, and in a panel of birds
      from five layer stocks. Twenty microsatellites, primarily of the poly(TG/AC)
      type, were polymorphic in at least one of the populations. Thirteen of the
      microsatellites were polymorphic in the East Lansing reference family and 13 were
      also polymorphic in the resource population, confirming that the genetic distance
      between White Rock and White Leghorn is about as great as between Jungle fowl and
      White Leghorn. Only six microsatellites were polymorphic in the Compton reference
      family, formed by a cross between two White Leghorn strains. Twelve of the
      microsatellites were mapped in the East Lansing and/or Compton reference
      families. These were well dispersed among the various linkage groups and did not
      show any indications of terminal clustering.

PMID- 8305089
TI  - Neurogenic communication disorders resulting from stroke.

PMID- 8305090
TI  - The emerging field of oral pharmaceuticals.

PMID- 8305091
TI  - Changes in knowledge of HIV/AIDS, sexual behaviour and practice among STD
      patients in Greenland 1990-1992. Monitoring the Stop-AIDS campaign in Greenland.
AB  - Due to a high incidence of STDs Greenland is considered to be a high risk area
      for an AIDS epidemic, and a close monitoring system has been set up to monitor
      the spread of HIV and changes in knowledge and sexual norms. This is the second
      report from surveys of knowledge, sexual behaviour and practice and STD patients
      i Greenland. Data were collected by means of self administered questionnaires in
      1990 to 1992 in Nuuk, Sisimiut and Angmagssalik. The results from Nuuk in 1992
      are compared with results from a similar survey from 1990.

PMID- 8305092
TI  - Growth patterns of Labrador Inuit youth: I. Height and weight.
AB  - The purpose of this study was to describe standing height and body weight
      recorded in 1991 from 32% (n = 100) of the Labrador Inuit youth aged between 5-18
      years living in Nain. The results demonstrated that females are taller than males
      until the age of 13 years. Growth in height seemed to level off at 15 years in
      females and 16 years in males. The greatest increase in height was between the
      ages of 11-13 years for females and 13-15 years for males. The largest increase
      in weight was between 12-16 years for both sexes. The data was compared with
      National Center for Health Statistics Growth Curves of United States youth. For
      this sample, height of the Labrador Inuit lies between the 10th and 50th
      percentiles, and weight lies between the 50th and 75th percentiles, while weight
      for height lies between the 75th and 95th percentiles. These results were similar
      to other studies of Inuit youth from Alaska, Canada and Greenland. In fact, the
      growth pattern of high weight for height demonstrated in Labrador seems to be
      typical of the Inuit population. Comparison of this data with that of stature
      recorded for Labrador Inuit between 1880-1928, although derived from small
      samples, suggests that a secular trend of increase in height with time for both
      sexes has occurred.

PMID- 8305093
TI  - The development of myopia up to the age of twenty and a comparison of refraction
      in parents and children.
AB  - As a part of a longitudinal birth cohort study, refraction was measured at the
      age of 20 years in 236 persons known to have had myopia at the age of 14 years
      and 266 controls (2982 refractions). The earlier the myopia had started, the more
      myopic the eyes were at the age of 20 years. The greatest mean refraction values,
      -4.94 D for males and -6.62 D for females were found when the change to myopia
      had started before the age of 10. The mean progression of myopia (the mean
      progression curves were achieved by calculating the mean refraction values at
      different ages) seems to continue at least to the age of 20. A female child with
      a myopic mother is more likely to develop myopia than a female child with a non
      myopic mother and the same relation holds good between a male child and his
      father. The myopic refractive error seems to be greater in the children than in
      their parents.

PMID- 8305094
TI  - Plasma concentrations of 25-hydroxyvitamin-D3 (calcifediol) as an indicator of
      ultraviolet radiation.
AB  - Vitamin D3 is produced in the skin of animals and humans by the sun's ultraviolet
      rays (UVB region, 290-315 nm). The main metabolite 25-hydroxyvitamin-D3 has a
      seasonal variation, depending on the ultraviolet radiation. In the Antarctic
      preliminary investigations on penguins (Pygoscelis papua), female sea elephants
      (Mirounga leonina), and humans showed that there was an increase in plasma 25
      hydroxyvitamin-D3 concentrations during UV-exposure in all three species. This
      metabolite can therefore be regarded as a molecular indicator of UV radiation.
      The possibility to use this compound in a long term monitoring program, for UV
      radiation, is under investigation.

PMID- 8305095
TI  - Use of a reflectance photometer as a diabetes mellitus screening tool under field
      conditions.
AB  - OBJECTIVE: Investigate the Accu-Chek II and visual Chemstrip bG methods for non
      insulin dependent diabetes mellitus (NIDDM) screening under field conditions with
      the aid of local providers. METHODS: Compare simultaneous random Chemstrip bG,
      Accu-Chek II and plasma glucose levels using a 6.7 mM cut-off, followed by a 75
      gram 2 hour oral glucose tolerance test while screening 1124 people in 15 Alaskan
      villages with the aid of local personnel during winter field conditions. RESULTS:
      The Accu-Chek II and visual Chemstrip bG methods detected 92% and 96%,
      respectively, of those newly diagnosed with NIDDM whose plasma screen was > or =
      6.7 mM. The Accu-Chek II provided correlations of 0.774, 0.850, 0.923, and 0.946
      with random, fasting, 1 and 2 hour plasma glucose. The mean Accu-Chek II,
      Chemstrip bG and plasma levels at which NIDDM was diagnosed were not
      statistically different. Receiver operator characteristic (ROC) curve analysis
      revealed optimum screening cut-off values for subsequent new diagnosis of NIDDM
      to be 8.3, 7.7, and 8.0 mM for visual, Accu-Chek II and hexokinase methods (p =
      NS). CONCLUSION: The Accu-Chek II and Chemstrip bG provided accurate glucose data
      in random NIDDM screening under field conditions with multiple local providers.

PMID- 8305096
TI  - The rotator crescent and rotator cable: an anatomic description of the shoulder's
      "suspension bridge".
AB  - Twenty fresh frozen cadaver shoulders were dissected in order to study the
      rotator cable-crescent complex. The rotator crescent is a term that we have used
      to describe the thin, crescent-shaped sheet of rotator cuff comprising the distal
      portions of the supraspinatus and infraspinatus insertions. The crescent was
      found to be bounded on its proximal margin by a thick bundle of fibers that we
      have called the rotator cable. This cable-crescent configuration was found to
      consistently span the insertions of supraspinatus and infraspinatus tendons. The
      dimensions of the rotator cable and crescent were measured by a digital
      micrometer. The rotator cable was found to be a very substantial structure,
      averaging 2.59 times the thickness of the rotator crescent that it surrounded.
      This anatomic study supports the concepts of stress-shielding of the rotator
      crescent by the stout rotator cable and stress transfer by this loaded cable
      system.

PMID- 8305097
TI  - Lateral patellar instability: treatment with a combined open-arthroscopic
      approach.
AB  - Lateral patellar maltracking, subluxation, and dislocation could arguably be
      grouped together as varying degrees of lateral patellar instability. Besides
      common anatomical etiological factors, such as genu valgum, patella alta, tibial
      rotation, and others, the author has found that many of these patients exhibit
      patellar hypermobility, a seldom mentioned physical finding. Lateral retinacular
      release fails to address the hypermobility, whereas traditional, more extensive
      open operations often carry significant postoperative morbidity and disability.
      This article suggests a surgical approach that combines open medial tethering of
      the patellar tendon with arthroscopic lateral release. The procedure addresses
      both etiological factors of anatomical peculiarity and patellar hypermobility,
      with a relatively benign postoperative course. In a series of 29 cases with
      follow-up of 4-8 years, results appear encouraging so far.

PMID- 8305098
TI  - Comparison of patella tendon versus patella tendon/Kennedy ligament augmentation
      device for anterior cruciate ligament reconstruction: study of results,
      morbidity, and complications.
AB  - In a study designed to evaluate the efficacy of supplementing patellar tendon
      bone-tendon-bone intraarticular anterior cruciate ligament (ACL) reconstructions
      with the polypropylene braid ligament augmentation device (Kennedy LAD; 3M,
      Minneapolis, MN), 75 consecutive patients treated between July 1988 and January
      1990 with isolated ACL disruptions in whom no associated ligament injury was
      present were offered the LAD as part of their preoperative consent. Interference
      screws at both bone plugs were used. Group I was composed of 25 patients (10
      acute, 15 chronic) with ACL disruptions who had the LAD added to their
      reconstruction. Group II was composed of 50 patients (24 acute, 26 chronic) who
      underwent an identical surgical procedure except that the LAD was not used.
      Objective and subjective assessments were made throughout the postoperative
      course, with the longest follow-up an average of 24 months postoperatively.
      Statistical analysis of these findings failed to show any statistically
      significant differences between the groups. Complications that occurred among the
      augmented group included infection, synovitis, effusion, and recurrence of
      instability, intraarticular adhesions, hemarthrosis, and painful hardware. This
      study demonstrates that the LAD added to the morbidity and severity in this
      series. It does not seem to improve results and is therefore not recommended for
      use in this manner.

PMID- 8305099
TI  - Graft-tunnel mismatch in endoscopic anterior cruciate ligament reconstruction: a
      new technique of intraarticular measurement and modified graft harvesting.
AB  - The purpose of this study was to determine the incidence of bitunnel interference
      fixation and accurate femoral insertion site targeting using a modified technique
      of endoscopic anterior cruciate ligament (ACL) reconstruction. Thirty-four
      consecutive central-third bone-patellar tendon-bone autograft modified endoscopic
      ACL reconstructions were prospectively studied. A new technique was used
      intraoperatively to directly measure (a) intraarticular (graft) distance (IAD)
      and (b) patellar tendon graft length, thereby allowing calculation of optimal
      tibial tunnel length for each case. Accuracy of guide pin placement through this
      tibial tunnel into the proposed femoral insertion site was assessed, as was the
      ability to achieve interference fixation in both tunnels (minimum of 20 mm bone
      interference fixation within the tibial tunnel). A new technique for patellar
      tendon-bone harvesting and proximal graft fixation to address graft mismatch is
      described. The average IAD from tibial origin to femoral ACL insertion measured
      26.3 +/- 3.0 mm (range 21-33). The average patellar tendon length (LP) was 48.4
      +/- 6.0 mm (range 40-63). The average calculated tibial tunnel length (TT)
      necessary to achieve bitunnel fixation (TT > or = LP + 20 - IAD) was 42.1 +/- 5.3
      mm (range 36-57). Establishment of the calculated tibial tunnel length was
      achieved in 25 cases (74%) (no graft-tunnel mismatch). Graft-tunnel mismatch, in
      which the tibial tunnel could not be established to the length calculated
      necessary to accommodate a minimum of 20 mm of bone graft, occurred in nine cases
      (26%). Graft-tunnel mismatch occurred more frequently in patients whose patellar
      lengths were > or = 50 mm (p < 0.005), but was not found to correlate
      specifically to IAD. Recession of the graft up into the femoral tunnel allowed
      accommodation of the mismatched graft (bitunnel interference screw fixation) in
      these nine cases, averaging 22.0 +/- 2.98 mm (range 16-29 mm) of available distal
      bone block fixation. Tibial tunnel fixation of > or = 20 mm was achieved in 30
      patients (88%), 18 mm in two, 17 mm in one, and 16 mm in one. Measurement error
      resulted in inadequate distal graft accommodation in four patients in whom error
      averaged 3 mm. Targeting of the femoral insertion site guide pin was achieved
      without requiring any knee manipulation for all cases. Patellar tendon graft
      protrusion through the tibial tunnel and potentially suboptimal graft fixation
      poses a frequent problem during endoscopic ACL reconstruction.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8305100
TI  - Suture anchor failure strength--an in vivo study.
AB  - Suture anchors are increasingly used to secure tendons or ligaments to bone.
      These devices are applicable for arthroscopic shoulder stabilization and rotator
      cuff repair. This study reports the in vivo characteristics of four anchors,
      including one absorbable anchor composed of poly-L-lactic acid. Failure strength
      and method of failure were recorded for these anchors as a function of time.
      Samples of four anchors [Mitek G2, Zimmer Statak, Acufex TAG wedge, and the
      absorbable Arthrex expanding suture plug (ESP)] were implanted into ram femurs
      and harvested at intervals. Each bone-anchor-suture system was stressed to
      failure. The failure force and failure method was recorded. Mitek G2 and Statak
      suture anchors failed consistently at 30 pounds by suture breakage. They had no
      implantation difficulties. The TAG wedge exhibited suture pull-out and implant
      flipping at insertion. The TAG wedge failed by suture cut-out, anchor pull-out,
      and suture breakage. Its average failure strength was initially 16 pounds, but
      increased to 28 pounds at 2 weeks and reached the 30-pound level by 4 weeks. The
      ESP poly-L-lactic acid anchors experienced implantation breakage in 20% because
      of their greater length and composition. At pull-out testing, the ESP failed by
      suture cut-out, anchor pull-out, and suture breakage. Failure strength was
      initially 27 pounds, was 17 pounds at 2 weeks, and increased to 30 pounds by 6
      weeks. The absorbable ESP does not have initial pull-out strength comparable with
      the Mitek and Statak suture anchors but does achieve this strength by 6
      weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305101
TI  - Comparison of ketorolac and opioid analgesics in postoperative ACL reconstruction
      outpatient pain control.
AB  - Pain control is an important postoperative consideration with any surgical
      procedure. Technological and procedural improvements have contributed to the
      reduction in both the degree of surgical difficulty and the postsurgical
      complications associated with intricate surgeries. As a result, certain surgeries
      have potential for being performed on an outpatient basis, dependent upon
      appropriate pain-management regimens and the degree of potential for
      postoperative complications. Arthroscopic anterior cruciate ligament (ACL)
      reconstruction is a common procedure. Because of the reduction in invasiveness
      that arthroscopy provides, outpatient surgery is now routinely employed for ACL
      patients. The arguments against ACL outpatient surgery have included the
      reluctance to use ambulatory, indwelling, intravenous pain-pump delivery systems
      for opioid pain medication. The purpose of this study was to determine the
      efficacy of a ketorolac tromethamine used for the management of the postoperative
      pain produced as a result of outpatient ACL reconstruction. When the ketorolac
      pain management regimen is compared in this setting with meperidine or morphine,
      pain control is as good as, or in some cases better than, either of the opioid
      drugs. Additionally, the adverse side effects associated with opioid drugs are
      significantly reduced at a substantially lower direct cost to the patient.

PMID- 8305102
TI  - Arthroscope-guided surgery versus nonoperative treatment for limited degenerative
      osteoarthritis of the femorotibial joint in patients over 50 years of age: a
      prospective comparative study.
AB  - Thirty-five patients with limited extent of degenerative osteoarthritis of the
      femorotibial joint treated by arthroscope-guided surgery were compared after 1-3
      years with 38 patients with a similar condition treated conservatively. In
      selecting a patient for arthroscope-guided surgery, the most important
      considerations were a normal mechanical axis, a limited extent of the
      degenerative process, and a femorotibial pain of sudden onset or that had been
      present for < 6 months. Clinical evaluation was undertaken using a modification
      of the Hospital for Special Surgery Knee Rating Score. The surgical procedure
      included partial meniscectomy, limited debridement of loose articular cartilage
      and removal of loose bodies. In the operated group, 26 patients (75%) showed
      improvement, five (14%) remained unchanged, and four (11%) were worse than before
      surgery. The average age of patients was 57 years. In the nonoperated group, six
      patients (16%) were improved, 12 (31%) unchanged, and 20 (53%) worse than before
      treatment. The average age of patients was 56 years. Arthroscope-guided surgery
      for limited degenerative osteoarthritis of the femorotibial joint with normal
      limb alignment or for degenerative meniscal tears has proven to be a useful
      technique.

PMID- 8305103
TI  - Arthroscopic use of the Herbert screw in osteochondritis dissecans of the knee.
AB  - This article describes repair of osteochondritis dissecans of the knee by
      arthroscopic Herbert screw fixation and reports the healing response and clinical
      results. Eleven patients were subjected to surgery using arthroscopy and all were
      affected by symptomatic osteochondritis dissecans of the medial femoral condyle.
      Average follow-up time was 16.3 months (13-29). One to four Herbert screws were
      used, either as the only fixation method or in conjunction with absorbable pins
      [poly (p-dioxanone)], depending on size and fragmentation of the injury. The
      patients were non-weight bearing for 10 weeks. The radiographic evidence of
      healing was correlated with the clinical outcome. The results were excellent or
      good in 81.8% of the patients. Arthroscopic Herbert screw fixation is an
      effective and safe method of repair for osteochondritis dissecans of the knee.

PMID- 8305104
TI  - Lesions of the subscapular tendon regarding two cases in arthroscopic surgery.
AB  - Subscapularis tendon lesions in the shoulder are usually difficult to diagnose
      through clinical examination alone. Isolated subscapularis tendon lesions are
      infrequent, and most of these injuries are associated with biceps tendon
      pathology, rotator cuff tears, fractures to the tuberosities, or as a part of an
      instability complex of the shoulder. All of these other diagnoses over-shadow and
      complicate the diagnosis of the subscapularis tendon. Although magnetic resonance
      imaging is frequently effective in evaluating subscapularis tendon tears,
      arthroscopy is certainly more efficient and affords the additional benefit of
      allowing surgical treatment of the lesion. The authors present two clinical cases
      and an update of the literature concerning this unusual lesion.

PMID- 8305105
TI  - Osteochondritis dissecans: a historical review and its treatment with cannulated
      screws.
AB  - The etiology of osteochondritis dissecans and the results of treating the early
      stages with arthroscopic fixation using cannulated screws is discussed.
      Arthroscopic surgery was performed on 14 patients with osteochondritis dissecans,
      and the osteochondral fragment was fixed with one or two screws. A second
      arthroscopic procedure was necessary to assess the lesion and remove the screws.
      Ambulation without weight bearing is allowed during the first 2 months
      postoperatively. Full range of motion is encouraged. The results indicate that
      all patients returned to their previous sport 3-11 months postsurgery. The
      authors conclude that fixation with cannulated screws is the ideal method of
      treating osteochondritis dissecans when the osteochondral fragment is still in
      its bed.

PMID- 8305106
TI  - Stiffness of the knee--mixed arthroscopic and subcutaneous technique: results of
      67 cases.
AB  - This study is an analysis of the treatment for mixed-cause stiffness of the knee:
      intraarticular and extraarticular. We examined 67 patients. The cause of
      stiffness was mostly ligamentous surgery, found in 51 cases (76%). Preoperative
      range of motion was 11 degrees extension and 89 degrees flexion. In 14 cases
      extension was complete. In the remaining 53 cases, extension was limited. Results
      achieved with arthroscopic arthrolysis were generally excellent. The ideal time
      to perform the operation is within the first 9 months after injury. The best
      results were obtained in the 7th month. Results deteriorate notably after 1 year.
      The age of the patient does not seem to affect the end result.

PMID- 8305107
TI  - Arthroscopic lysis in knee arthrofibrosis.
AB  - Arthrofibrosis continues to be a difficult complication in articular surgery on
      the knee. We present our experience in 21 cases of arthroscopic lysis as an
      alternative to mobilization under anesthesia. The technique begins with the
      liberation of the adhesions of the suprapatellar pouch, continues down both
      gutters, and ends with a cleaning of the notch where necessary. When a
      restriction of patellar mobility persists, we make a retinacular release. The
      results obtained are very satisfactory, with an average increase in the arc of
      mobility of 68 degrees. The average gain in mobility at 6 months is significantly
      greater than that achieved in the immediate postoperative period. Longer follow
      up showed no improvement in range of motion after 6 months.

PMID- 8305108
TI  - Osteochondritis dissecans of the anterior tibial spine.
AB  - A 12-year-old boy had a history of pain in the right knee for 2 months, mainly
      pain in extension. He could not recall any trauma to the knee. The radiograph
      suggested osteochondritis dissecans in the anterior spine. An arthroscopy was
      performed and a prominence in the tibial insertion of the anterior cruciate
      ligament in the anterointernal area was observed, and the fragment resected. The
      diagnosis of osteochondritis dissecans was confirmed by pathological study. As
      far as we are aware, this is the first case describing this new location.

PMID- 8305109
TI  - Posterior superior impingement of the rotator cuff on the glenoid rim as a cause
      of shoulder pain in the overhead athlete.
AB  - A case of impingement of the deep surface of the supraspinatus tendon on the
      posterior superior rim of the glenoid and mild anterior laxity has been
      presented. The partial-thickness tear of the undersurface rotator cuff tendon,
      degenerative tear of the posterior superior labrum, and osteochondral impression
      fracture of the humeral head have been documented. The purpose of this case
      report is to present the pathological findings associated with posterior superior
      glenoid rim impingement and emphasize its role as a cause of shoulder pain in the
      overhead athlete. In addition it is important to stress the fact that shoulder
      pain in the overhead athlete may be multifactorial.

PMID- 8305110
TI  - Osgood-Schlatter's disease complicating anterior cruciate ligament
      reconstruction.
AB  - Osgood-Schlatter's disease (OSD) is generally felt to be a benign self-limited
      disorder. In a small number of patients a symptomatic free bone ossicle persists
      at the tibial insertion of the patellar tendon. We report the case of a
      collegiate soccer player with a history of OSD who sustained an acute rupture of
      his anterior cruciate ligament (ACL). The presence of a free bone ossicle in his
      patellar tendon necessitated modification of our routine approach to ACL
      reconstruction. Awareness of the potential for patellar tendon graft problems in
      patients with previous OSD will allow surgeons to plan alternative reconstructive
      techniques based on the specific needs of the patient.

PMID- 8305111
TI  - Magnetic resonance imaging diagnosis of discoid medial meniscus.
AB  - A case of discoid medial meniscus of the massive type diagnosed preoperatively by
      magnetic resonance imaging is presented. Additionally, the preoperative studies
      and arthroscopic findings are presented.

PMID- 8305112
TI  - Arthroscopic diagnosis and treatment of septic arthritis of the hip joint.
AB  - Septic arthritis of the hip joint can be difficult to detect clinically and
      usually requires a formal arthrotomy for adequate drainage and debridement of the
      joint. This case report presents a patient for whom the diagnosis and treatment
      were performed arthroscopically. This technique allows isolation of the organism
      as well as the opportunity to irrigate, lavage, and debride the joint through a
      small puncture wound only.

PMID- 8305113
TI  - Posteromedial ankle impingement.
AB  - We present a case of soft tissue impingement in the posteromedial ankle, which
      has not been previously reported. When a patient presents with chronic
      posteromedial ankle pain and swelling, clinicians should be suspicious of soft
      tissue impingement in the posteromedial ankle. Pertinent history and physical
      examinations are most helpful in the diagnosis of this lesion. Arthroscopic
      debridement of the hypertrophic soft tissue is successful in returning the
      patient to his or her previous activities.

PMID- 8305114
TI  - Arthroscopic placement of the interference screw for anterior cruciate ligament
      reconstruction.
AB  - This article describes a simple technique to check arthroscopically the position
      of the interference screw in bone patellar tendon bone reconstruction of the
      anterior cruciate ligament. With this simple and inexpensive method we can be
      sure that the bone plug in the tunnel has a rigid fixation and that the screw
      does not damage that graft.

PMID- 8305115
TI  - The arthroscopic "impingement test" during anterior cruciate ligament
      reconstruction.
AB  - A primary goal of ACL reconstruction is to avoid graft impingement, which may
      lead to loss of motion and/or an increased incidence of instability. Although
      surgeons are cognizant of this potential problem, the intraoperative correction
      of graft impingement is technically demanding because the graft-notch
      relationship is obscured by the trochlea articulating with the tibial plateau
      during the final 10 degrees of extension. We present a simple impingement test
      that is performed before graft insertion and fixation to help avoid this
      potential pitfall.

PMID- 8305116
TI  - [CT and MRI in tumors of the mouth and oropharynx--comparison of methods with
      reference to fast and ultra-fast MR pulse sequences].
AB  - A total of 488 patients with neoplasms (in 474 cases with malignant tumours) of
      the oropharynx, floor of the mouth and oral cavity, were examined with MRI and
      CT. MRI proved superior to CT, on account of its coronal and sagittal slice
      orientation enabling not only a better demonstration of findings, but also
      improved tumour detection and staging. The diagnostic value of MRI was further
      enhanced with additional fast and ultrafast MR sequences rather than spin echo
      sequences alone, as previously practised.

PMID- 8305117
TI  - [Temporary sagittal mandibulotomy as an approach to the pterygopalatine fossa,
      the parapharyngeal space and the oropharynx].
AB  - Standard procedures for temporary mandibulotomy are medial or the lateral
      osteotomy. Median mandibulotomy is associated with destruction of anatomical
      structures in the floor of the mouth and with lateral osteotomy no preservation
      of the nervus alveolaris inferior is possible. Therefore, a modification of
      mandibulotomy is described with wide-field exposure, minimal functional defects
      and reduction of osteotomy-related complications. The first osteotomy is carried
      out vertically before the foramen mentale on the buccal compacta of the mandible.
      A second vertical osteotomy is placed on the lingual compacta posterior to the
      musculus myohyoideus. Horizontal osteotomies on the alveolar ridge and the basal
      ridge of the mandible are connected with the vertical osteotomies. Using a
      chisel, the lingual and the buccal part of the mandible are split sagittally with
      preservation of the nervus alveolaris inferior located in the buccal fragment of
      the mandible. The two parts of the mandible are divided to provide access to the
      oropharynx. Surgical approach to the fossa pterygopalatina and the parapharyngeal
      space is reached with dissection of the mucosa along the ascending mandible,
      subluxation in the mandibular joint and reflection of the mandible cranially and
      posteriorly. The wide access offers a lot of advantages especially in combination
      with a microvascular flap reconstruction. Fixation of the mandible is carried out
      with two titanium miniplates at the anterior vertical osteotomy. The wide areas
      of the split bone marrow, resulting from sagittal splitting, achieved an exact
      adaptation of the mandibular parts and an easy and sure fixation via miniplates.
      Therefore, post-operative radiation therapy can be started two weeks after the
      operation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305118
TI  - [Differential indications of free and pedicled transplants in reconstructive
      surgery in the head and neck area].
AB  - Since the microvascular tissue transfer has been introduced in the reconstructive
      surgery of the head and neck the question arises repeatedly which free transplant
      should be favoured and which advantages exist to pedicled flaps. Based on our
      experiences in 243 reconstructions we discuss the advantages and disadvantages of
      different operative techniques and their differential indications. Using free as
      well as pedicled flaps, reconstructions can be performed individually and the
      decision for a transplant depends on localisation, size and depth of the defect.
      In contrast to conventional techniques, like the deltopectoral flap, which we
      performed a decade ago, both new principles allow a one-stage procedure, which
      reduces the period of hospitalisation and improves the quality of life for the
      patients. The advantages of free tissue transfer can be seen especially in the
      reconstruction of the upper digestive tract after laryngopharyngectomy. The
      existing form of the jejunum segment like a tube allows an easy one-stage
      reconstruction, as well as better functional and aesthetic results. The radial
      forearm flap is a nearly ideal transplant in the anterior oral cavity because of
      the mechanical stability. In contrast the jejunum patch is more vulnerable and
      less qualified especially when fitting a prosthesis. In the posterior oral cavity
      we prefer the jejunum patch because it allows more mobility of the tongue. Deep
      defects, for instance after glossectomy, should be reconstructed with a free
      latissimus-dorsi-flap or a pedicled myocutaneous pectoralis major flap. In
      contrast to free tissue transfer, pedicled flaps have the advantage that the
      difficult technique of microanastomosis is avoided, which reduces the
      complication rate and the operation time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305119
TI  - [Combined surgical flaps for simultaneous reconstruction of the tongue, mouth
      floor and pharynx in expanded glossectomy within the scope of multi-modal
      treatment of squamous epithelial cancers of UICC stage IV].
AB  - Multimodal approach and improved surgical techniques enable the head and neck
      surgeon to operate even far advanced tumours of the head and neck under curative
      intention. Microanastomosed distant flaps and intestinal grafts expanded the
      operative spectrum while having the disadvantages of being time-consuming and in
      most cases the necessity to call for the specialist (e.g. the abdominal, vascular
      surgeon). In 6 cases of total glossectomy combined with hemipharyngectomy and
      hemimandibulectomy the possibilities of closing large defects by combined
      regional and pedicled flaps in the head and neck area are shown. In all of our
      cases surgical therapy had been placed at the end of therapeutic interventions in
      a multimodal treatment protocol. Treatment started with induction chemotherapy
      with a regimen including cisplatin, bleomycin and vindesin sulfate and was
      followed by a subsequent radiotherapy reaching a total reference dose of 60 to 70
      Gy. After radiotherapy 5 patients received adjuvant chemotherapy of 1-4 cycles.
      Despite the aggressive presurgical treatment, the postoperative complications
      were minor. In a median survival of 37.5 months there were 3 recurrences, 2
      patients died of tumour progression. All of our patients benefited from of the
      "salvage-operation" especially with regard to tumour pain. Quality of the
      patients' life could be improved upon by percutaneous endoscopic gatrostomy (PEG)
      and as well good functional and cosmetic results of the surgical reconstructions.
      The results justify the discussion about a palliative indication of extended
      surgical procedures and reconstructive surgery in far advanced head and neck
      cancer in the course of a multimodal treatment regimen.

PMID- 8305120
TI  - [200 free jejunum transplantations: is the great surgical effort worthwhile?].
AB  - From 1983 to 1992, 216 free jejunal transplants were performed after resection of
      malignant tumours for reconstructing the upper oesophageal tract. In two patients
      reconstruction was performed secondarily and in four cases within the framework
      of recurrence treatment. In 25 cases the jejunal transplant was sewn in tubular
      form to the circular insert of the hypopharynx, whereas in the remaining 188
      cases the jejunum transplant was sewn as patch. A jejunum transplant was most
      frequently employed in the tonsillar region (n = 75). Reconstruction of the body
      of the tongue was performed in 42 cases and of the hypopharynx in 29 cases. Of
      the 213 patients treated, 175 were irradiated postoperatively. The most severe
      complications were in 5 cases death from the sequels of the operating, abdominal
      complications in 15 cases and complete loss of the transplant in 22 cases.
      Protracted inability to swallow occurred in 15 cases and pneumonia in 16
      patients. The five-year survival probability was 39% for the 42 patients
      suffering from carcinomas of the oral cavity, 53% for the 90 patients with
      oropharyngeal carcinoma in stage III and 33% in stage IV, as well as 40% with the
      29 patients suffering from hypopharyngeal carcinomas. An essential advantage of
      the free jejunum transplants were the excellent functional reconstruction
      results. This is demonstrated by examples of various cases. Since the number of
      treated patients is still too low, it is at present not yet possible to compare
      this approach with other therapeutic concepts, such as enoral laser surgery
      resection or radiochemotherapy.

PMID- 8305121
TI  - [Balloon occlusion test of the internal carotid artery for evaluating
      resectability of blood vessel infiltrating cervical metastasis of advanced head
      and neck cancers--Heidelberg experience].
AB  - During the last two years 17 patients of the ENT-Department of the University of
      Heidelberg suffering from squamous-cell carcinomas of the head and neck underwent
      a balloon occlusion test of the internal carotid artery (ICA). The investigation
      was performed because of tumorous infiltration of the large cervical vessels. The
      balloon occlusion of the ICA was accomplished at the Department of Neuroradiology
      of the University of Heidelberg. While stopping bloodflow in the ICA of one side
      for 15-20 min, clinical, electrophysiological and Doppler sonographic monitoring
      was performed, to detect severe cerebral complications. The specific
      electrophysiological monitoring contained the detection of MSSEP's (median nerve
      stimulated somatosensorial evoked potentials) and TCMEP's (transcortical motor
      evoked potentials) during test occlusion. Balloon occlusion was not possible in
      three patients because of severe arteriosclerosis. Test occlusion had to be
      discontinued in three patients because of clinical complications (temporary
      amaurosis, orthostatic complications). Finally, seven patients showed
      contraindications during test occlusion for permanent occlusion of the ICA. Four
      patients had a permanent occlusion of the ICA after tumour resection. In two
      patients the ICA was removed without problems in test occlusion. The third
      patient underwent a permanent carotid occlusion because of bleeding complications
      (in spite of poor clinical tolerance of the test occlusion). In the fourth
      patient, only intraoperative neuromonitoring with MSSEP's was conducted before
      permanent carotid occlusion. All four patients did not show any neurological
      deficits after resection of the ICA. Neurophysiological monitoring played an
      important role in predicting cerebral complications after permanent occlusion of
      the ICA.

PMID- 8305122
TI  - [Further development in TNM classification of laryngeal cancers].
AB  - To prepare an improved TN classification of laryngeal carcinomas, a great number
      of serial sections of laryngeal cancers and neck dissection specimens has been
      investigated and corresponding studies of clinical relevance were performed. Our
      proposals have been accepted in the 1993 supplement of the TNM-UICC
      classification and will be tested within the frame of so-called ramification
      studies. The authors propose that the T-category of laryngeal carcinomas should
      no longer be determined by anatomical areas of different sizes, but by
      millimetres only (up to 15 mm T1, 15-25 mm T2 a, 25 mm and more without impaired
      mobility T2 b, to impaired mobility or fixation of vocal cords T3, or T4 if the
      tumour extends beyond the larynx. The pT categories correspond to the T
      categories. A histological depth of or less than 5 mm is pT 1 or 2. It is
      proposed that the differentiation into glottic and subglottic tumours of the
      larynx should be abandoned. In lymph node metastases, the size, number, level and
      extranodular spread are considered. N1 and N2 are metastases in the upper two
      thirds of the neck without fixation (extranodal spread). N1 are one or two
      ipsilateral metastases of 2 cm or less in diameter, N2 are metastases of more
      than 2 cm diameter or bilateral metastases. N3 are fixed metastases or metastases
      in the lower third of the neck. Our proposals are presented in tables,
      ramification tables, conversion tables and a documentation sheet.

PMID- 8305123
TI  - [Uni- and multivariate analysis of prognostic factors in T3 laryngeal cancers].
AB  - In 511 patients with T3N0-3M0 laryngeal carcinoma, 24 possible prognostic factors
      were analysed retrospectively. The factors were age, sex, mode of treatment,
      duration of several clinical symptoms, the presence of sore throat, otalgia,
      dyspnoea, and dysphagia, previous tracheotomy, tumour extension, lymph node
      status (five items), histologic grading, smoking habits, and alcohol intake. For
      300 patients in whom surgery was part of the primary treatment, pathologic
      staging of the primary tumour and of lymph nodes in neck dissection specimens,
      cartilage invasion, radicality of the operation, differentiation grade, and
      subglottic extension were also evaluated. Univariate analysis revealed prognostic
      significance on survival for tumour extension (limited to the glottic region),
      lymph node status (clinically palpable lymph nodes, cytologically confirmed
      positive lymph nodes), level of lymph node metastasis (high and midjugular site),
      histologic grading (poor differentiation grade), and treatment modality (planned
      combined therapy). In the group that underwent surgery, all factors derived from
      specimens of the larynx and neck dissections had prognostic significance.
      Multivariate analysis revealed that the glottic site of the tumour, the presence
      of cyto- and histopathologically proven metastatic lymph nodes, pretreatment
      tracheotomy, positive resection margins, and planned combined treatment had a
      significant influence on corrected actuarial survival.

PMID- 8305124
TI  - [Manual lymph drainage in the area of the head and neck?].

PMID- 8305125
TI  - Thyroid and adrenal dysfunction in abstinent alcoholic men: locus of disturbance.
AB  - Certain neuroendocrine abnormalities (e.g., blunted plasma adrenocorticotropic
      hormone [ACTH] response to corticotropin-releasing hormone [CRH] administration
      and blunted serum TSH response to thyrotropin-releasing hormone [TRH]
      administration) are common in alcoholic patients. It was the objective of this
      study to evaluate whether they are centrally mediated: that is, whether they are
      secondary to increased activity of CRH and/or TRH neurons. We evaluated the
      nocturnal secretion (2200 hours to 1000 hours, q 15 min) of plasma ACTH, serum
      cortisol, and serum TSH, and their responses to the combined administration of
      CRH and TRH, in 28 acutely abstinent alcoholic (age range: 32 to 57 years; mean:
      42.4 years) and 19 normal men (age range: 21 to 52 years; mean: 32.1 years). To
      assess the validity of administering CRH and TRH simultaneously, we gave 10
      additional abstinent alcoholic men (age range: 36 to 53 years; mean: 45.8 years),
      in random order and at least 4 days apart, either CRH, TRH, placebo, or CRH plus
      TRH. Nocturnal ACTH, cortisol, and TSH secretion, as well as cortisol and TSH
      responses after CRH plus TRH administration, were similar in alcoholic and normal
      men. However, ACTH peak responses to CRH plus TRH were reduced in the alcoholic
      men (p < 0.05). The ACTH, but not cortisol, response was greater after combined
      CRH plus TRH administration than after CRH alone (p < .002). The blunted ACTH
      response does not appear to be the result of increased endogenous CRH activity,
      because all parameters of nocturnal ACTH pulsatility were normal in the
      alcoholics. It rather appears to be secondary to an intrinsic defect in the CRH
      responsiveness of the pituitary corticotroph, possibly due to genetic
      vulnerability or to the toxic effects of prolonged alcohol abuse.

PMID- 8305126
TI  - Evidence that the M1 muscarinic receptor subtype mediates the effects of
      oxotremorine on masculine sexual behavior.
AB  - The cholinergic system participates in the regulation of masculine sexual
      behavior, mainly through the muscarinic system. Recently, muscarinic receptors
      have been subdivided into at least two subtypes, M1 and M2, according to their
      differential affinity for pirenzepine. In this study, we analyzed the possible
      participation of the M1 muscarinic receptor subtype on masculine sexual behavior
      regulation. In the first experiment, trihexyphenidyl, a specific M1 antagonist,
      was administered to experienced adult male rats in a wide range of doses (from
      0.1 to 6.4 mg/kg). No modification was observed in any of the male sexual
      behavior parameters recorded, with the exception of the highest dose at which an
      increase of the intromission frequency and a decrease of the ejaculation
      frequency were observed. In the second experiment, trihexyphenidyl was
      administered in several doses (from 0.2 to 1.6 mg/kg), before the administration
      of oxotremorine, a muscarinic agonist, at a dose that readily facilitates
      masculine sexual behavior. Trihexyphenidyl completely prevented the facilitatory
      effects of oxotremorine even at the smallest dose used. These results strongly
      suggest that the M1 muscarinic receptor subtype participates in the cholinergic
      facilitation of masculine sexual behavior.

PMID- 8305127
TI  - Electrical stimulation of the medial prefrontal cortex increases dopamine release
      in the striatum.
AB  - Exogenous and endogenous glutamate has been shown to evoke dopamine (DA) release
      in the striatum using both in vitro and in vivo techniques. We hypothesized that
      stimulation of the prefrontal cortex (PFC) would phasically enhance striatal DA
      release via the glutamatergic corticostriatal pathway. To test this hypothesis,
      in vivo brain microdialysis was employed to measure extracellular concentrations
      of DA in the striatum during electrical stimulation of the PFC. Five rats were
      implanted with bilateral electrodes located in the medial PFC and dialysis probes
      in the dorsal striatum. Two days later the PFC of these awake, freely moving rats
      was stimulated first at 50 microA and then at 100 microA for 20 minutes at 2-hour
      intervals. Both currents significantly increased DA release. Extracellular DA
      rose rapidly during stimulation, peaked immediately afterward, and then slowly
      returned to baseline values. Dopamine reached 118% of baseline values with 50
      microA stimulation and 138% with 100 microA stimulation. Histologic analysis
      using the fluorescent retrograde dye Fluoro Gold confirmed that cells projecting
      to the vicinity of the striatal dialysis probe originated in the vicinity of the
      PFC electrodes. These results provide direct evidence for phasic, excitatory
      modulation of striatal DA release by the PFC.

PMID- 8305128
TI  - The functional neuroanatomy of Tourette's syndrome: an FDG-PET study. I. Regional
      changes in cerebral glucose metabolism differentiating patients and controls.
AB  - Regional metabolic rates for glucose estimated using [18F]fluorodeoxyglucose
      positron-emission tomography were compared in 16 drug-free patients with
      Tourette's syndrome (TS) and 16 age- and sex-matched normal volunteers.
      Tourette's syndrome patients were characterized by decreased normalized metabolic
      rates in paralimbic and ventral prefrontal cortices, particularly in
      orbitofrontal, inferior insular, and parahippocampal regions. Similar decreases
      were observed in subcortical regions, including the ventral striatum (nucleus
      accumbens/ventromedial caudate) and in the midbrain. These changes were more
      robust and occurred with greater frequency in the left hemisphere. They were
      associated with concomitant bilateral increases in metabolic activity the
      supplementary motor, lateral premotor, and Rolandic cortices. Effects of prior
      exposure to neuroactive drugs did not account for these findings. These results
      suggest that an altered relationship between limbic-related regions of the cortex
      and striatum and cortical regions involved in the initiation of movement may play
      a role in the pathogenesis of this illness.

PMID- 8305129
TI  - Multiple ways to cellular immune tolerance.
AB  - Both central and peripheral pathways leading to T-cell tolerance were discussed
      at a recent meeting. The mechanisms that maintain self tolerance, as well as the
      conditions in which self-reactive T cells launch an autoaggressive attack, were
      specially emphasized.

PMID- 8305130
TI  - Delayed hypersensitivity, immune deviation, antigen processing and T-cell subset
      selection in syphilis pathogenesis and vaccine design.
AB  - T-cell mediated delayed-type hypersensitivity (DTH) is the predominant immune
      mechanism for clearing tissues of infecting organisms in the primary lesion of
      syphilis. Here, Stewart Sell and Pei-Ling Hsu propose a strategy for vaccination
      against syphilis in which selective induction of DTH may be accomplished by using
      BCG vectored vaccines containing selected DNA sequences for T. pallidum antigens.

PMID- 8305131
TI  - Programmed cell death, apoptosis and killer genes.
AB  - A cursory examination of the literature reveals that the study of programmed cell
      death and apoptosis is increasing exponentially. Most contributors to this field
      have come either from developmental biology or immunology and view programmed
      cell death from different perspectives, leading both to confusion and an
      inability to fully appreciate the literature from other disciplines. Here,
      Lawrence Schwartz and Barbara Osborne define the terms and ideas relevant to the
      study of cell death in a way that will be accessible to investigators from all
      fields.

PMID- 8305132
TI  - How alpha beta T-cell receptors 'see' peptide/MHC complexes.
AB  - Recent results have added new information to our understanding of alpha beta T
      cell receptor mediated recognition. In particular, we find that the V(D)J
      junction or 'CDR3' portion of TCR alpha and beta seem most important in
      contacting peptides bound to MHC molecules, consistent with previous predictions.
      Surprisingly, these same CDR3-peptide contacts also appear to have a major
      influence on the TCR-MHC molecule interactions as well.

PMID- 8305133
TI  - Tickling the TCR: selective T-cell functions stimulated by altered peptide
      ligands.
AB  - Recent observations of T-cell responses following T-cell receptor (TCR)
      interaction with altered peptide ligands have highlighted the complexity of this
      signalling system. The indications are that the TCR responds to minor changes in
      ligand with gradations of T-cell activation and effector functions. Brian
      Evavold, Joanne Sloan-Lancaster and Paul Allen review these studies and present a
      model in which partial T-cell activation and TCR antagonism are related events in
      a continuum of signalling through the TCR.

PMID- 8305134
TI  - Many cytokines and interleukins bind to glycosaminoglycans.

PMID- 8305135
TI  - Light organ symbioses in fishes.
AB  - Most bioluminescent fishes are self-luminescent, but a substantial minority of
      bioluminescent teleosts produce light that is due to symbiotic luminous bacteria
      housed in elaborate light organs. The majority of symbiotically bioluminescent
      fishes (ten families in five orders) harbors common free-living species of marine
      luminous bacteria: Photobacterium phosphoreum, P. leiognathi, and P. fischeri (=
      Vibrio fischeri). Others, associated with the beryciform family Anomalopidae and
      nine families in the lophiiform suborder Ceratioidei, have apparently obligate
      symbionts that have recently been identified by small subunit (16S) rRNA analysis
      as new groups within the genus Vibrio. This article summarizes what is currently
      known about relationships between light organ symbionts and their hosts,
      including characteristics of light organ environments, physiology of light organ
      symbionts, and the evolution of light organ symbionts and their associations.

PMID- 8305136
TI  - Petroleum spill bioremediation in marine environments.
AB  - Bioremediation is a promising technology for responding to marine oil spills. A
      majority of molecules in crude oils and refined products are biodegradable, and
      they will eventually leave the environment as they are consumed by microbes.
      Bioremediation aims to stimulate the rate of this process. Successful
      bioremediation efforts have so far focused on applying fertilizers to aerobic
      oiled shorelines to at least partially relieve the nitrogen limitation of
      biodegradation by indigenous microorganisms. Nevertheless, there seems to be room
      for improving the process by developing better fertilizers, developing
      surfactants to stimulate degradation, and perhaps using exogenous bacteria. There
      also is room to extend the application to oiled marshes and other anaerobic
      sediments, and perhaps to floating slicks. This review covers our present
      understanding of hydrocarbon degradation in the marine environment, and discusses
      field trials and field use of bioremediation as an important adjunct to other
      tools for responding to marine oil spills.

PMID- 8305137
TI  - Computed tomography (CT) and magnetic resonance imaging (MRI) of pleural masses.
AB  - Depending on the location, size, and underlying histologic features, pleural
      masses may produce a large spectrum of findings. While a number of imaging
      modalities may be used, plain chest radiographs remain the most common
      examination in the initial assessment of these patients. In this article, we
      review the use of two noninvasive techniques: computed tomography and magnetic
      resonance imaging. For the purpose of this review, localized pleural masses and
      diffuse pleural masses are discussed separately. Among the various pleural
      masses, metastatic disease represents the most frequent neoplasm.

PMID- 8305138
TI  - Analysis of antigenic characteristics of Rickettsia tsutsugamushi Boryong strain
      and antigenic heterogeneity of Rickettsia tsutsugamushi using monoclonal
      antibodies.
AB  - Twenty-four monoclonal antibodies were produced by immunizing BALB/c mice with
      Rickettsia tsutsugamushi Boryong strain and used for the analysis of antigenic
      characteristics of R.tsutsugamushi Boryong strain and antigenic heterogeneity of
      R.tsutsugamushi by indirect immunofluorescent(IF) test. R. tsutsugamushi Kato,
      Karp, Gilliam, TA686, TA716, TA763, TC586, TH1817, and Boryong were used for the
      analysis of antigenic heterogeneity of R.tsutsugamushi. Five monoclonal
      antibodies were reactive with 27-kDa protein, four monoclonal antibodies were
      reactive with 47-kDa protein, and eight monoclonal antibodies were reactive with
      56-kDa protein of R.tsutsugamushi Boryong strain. The reactive protein of seven
      monoclonal antibodies could not be identified by immunoblotting method. All
      monoclonal antibodies to 27-kDa protein and three monoclonal antibodies to 47-kDa
      protein, and five monoclonal antibodies to 56-kDa protein were reactive with
      three to eight strains among nine strains of R. tsutsugamushi tested. One
      monoclonal antibody reactive to 47-kDa protein(KI18) and two monoclonal
      antibodies reactive to 56-kDa protein(KI36, and KI37) reacted with all the
      strains of R. tsutsugamushi tested. Strain-specific monoclonal antibody(KI58)
      could be found among antibodies which were reactive with 56-kDa protein. There
      was no strain which showed same reactivity pattern to these 24 monoclonal
      antibodies among nine strains. From this results, it could be concluded that
      Boryong strain is antigenically different from other strains of R.tsutsugamushi
      and antigenic heterogeneity of R.tsutsugamushi is due to the antigenic diversity
      of several proteins of R. tsutsugamushi including 56-kDa protein.

PMID- 8305139
TI  - Patterns of p53 expression in phyllodes tumors of the breast--an
      immunohistochemical study.
AB  - Authors performed an immunohistochemical analysis using monoclonal antibody to
      p53 protein on 15 cases of benign and malignant phyllodes tumor of the breast
      along with a review of other conventional clinicopathological parameters to
      investigate the meaning of p53 expression. The cases were composed of 8 benign
      and 7 malignant lesions. The pattern of p53 expression showed a statistically
      significant difference between these benign and malignant lesions (p < 0.005).
      None of the benign cases expressed p53 whereas 6 out of 7 malignant cases did.
      Among malignant phyllodes tumors, the pattern of expression was diffuse and
      strong in two cases while granular and relatively weak in the remaining 4 cases.
      p53 expression seemed to be a unique feature of malignant phyllodes tumors,
      thereby, one of the most significant parameters for the differentiation of benign
      and malignant phyllodes tumors of the breast.

PMID- 8305140
TI  - Hallervorden-Spatz syndrome in two siblings diagnosed by the clinical features
      and magnetic resonance imaging (MRI).
AB  - Hallervorden-Spatz syndrome (HSS) is a heredodegenerative disorder characterized
      by both progressive pyramidal and extrapyramidal signs, dysarthric speech, and
      mental deterioration. No diagnostic biochemical test is yet available, and
      diagnosis of HSS can be confirmed only at autopsy by the characteristic
      neuropathology including abnormal iron storage, disordered myelination, and loss
      of brain substance. We present two siblings with clinical features consistent
      with HSS, in whom magnetic resonance imaging (MRI) demonstrated the deposition of
      iron in the globus pallidus and the substantia nigra thus allowing an antemortem
      diagnosis of HSS.

PMID- 8305141
TI  - Botulinum a toxin treatment of hemifacial spasm and blepharospasm.
AB  - We studied the effects of botulinum A toxin in 101 patients with hemifacial spasm
      and 11 patients with blepharospasm in an open trial and double blind manner. All
      patients in the open trial and 6 patients in the double blind trial improved
      after the first injection of botulinum toxin. There was no improvement with
      placebo. The peak effect ranged from one to 6 days after injection and mean peak
      effect was 3.6 days in blepharospasm, and 4 days in hemifacial spasm. Of 144
      treatments, 98.6% had excellent results, (below grade I). The duration of
      beneficial effect ranged 11 to 40 weeks (mean 16.5 weeks) in hemifacial spasm and
      9 to 30 weeks (mean 14.2 weeks) in blepharospasm. Complications were encountered
      in 63.4% in hemifacial spasm and 72.7% in blepharospasm. The common side effects
      were dry eyes, mouth droop, ptosis and lid edema in order of frequency. These
      side effects were mild and resolved spontaneously in 1 to 3 weeks. Botulinum A
      toxin therapy is effective and convenient, and the treatment of choice for
      patients with hemifacial spasm and blepharospasm.

PMID- 8305142
TI  - Spinal congenital dermal sinus--experience of 5 cases over a period of 10 years.
AB  - Spinal congenital dermal sinus (CDS) is a rare entity which supposedly results
      from the failure of the neuroectoderm to separate from the cutaneous ectoderm
      during the process of neurulation. The lesions are most frequent at the
      lumbosacral followed by the occipital region. CDS of the thoracic region is very
      rare. The patients with spinal CDS present with meningitis and/or mass effect
      from the associated inclusion tumor. They are usually dermoid or epidermoid
      cysts. Teratoma is rarely associated. The authors experienced 5 cases of spinal
      CDS over a 10 year period. Of the 5 cases, 2 were at thoracic and 3 were at
      lumbosacral levels. Dermoid cyst, epidermoid cyst and teratoma were associated in
      one case each. Two cases presented with neurological deficit and meningitis while
      an additional case presented with neurological deficit and a history of probable
      meningitis. Pain was present in 2 cases. Magnetic resonance imaging played an
      important role in the diagnosis of the lesion and planning of surgery. All the
      cases showed a good response to surgery even though one patient had persistent
      neurological deficit.

PMID- 8305143
TI  - Flow cytometric DNA analysis of gastric cancer--correlation with histology and
      clinical outcome.
AB  - Nuclear DNA content was analysed by means of flow cytometric measurements in 103
      patients with gastric carcinomas, using paraffin-embedded archival tissue. DNA
      aneuploidy was found in 40 cases (38.8%). The mean DNA index of aneuploid tumors
      was 1.45(range 1.13 to 2.37). No significant association between ploidy and
      either age, sex, tumor location, size, stage, growth pattern, or histologic type
      was found. However, the incidence of aneuploidy was higher in high grade
      carcinomas than in low grade carcinomas; the incidence of aneuploidy was 10%,
      68.8%, and 45.8% for Grade II, III, and IV carcinomas, respectively, as compared
      with Grade I carcinomas which were all diploid. On statistical analysis, Abnormal
      cellular DNA content was significantly correlated with high histologic grade (P <
      0.005). Patients with aneuploid cancer (39.2%) had a poorer prognosis than those
      with diploid cancer (70.0%) based on (P < 0.01). The 2-year survival rate for
      advanced gastric carcinoma. Therefore, DNA ploidy might be a useful prognostic
      factor in cases of advanced gastric cancer.

PMID- 8305144
TI  - Expression of alpha-smooth muscle actin in liver diseases.
AB  - To evaluate the distribution of alpha-smooth muscle actin (alpha-SMA) positive
      cells in various liver diseases, we undertook an immunohistochemical study of
      liver diseases including chronic persistent hepatitis, chronic active hepatitis,
      liver cirrhosis, intrahepatic cholelithiasis and hepatocellular carcinoma. As a
      control, fetal livers (gestational age: 22-26 weeks) showed alpha-SMA positive
      cells along the blood vessels of the portal area, terminal hepatic venules and at
      perisinusoidal spaces. Perisinusoidal alpha-SMA positive cells were bipolar
      shaped and had round nuclei. In chronic persistent hepatitis, a few alpha-SMA
      positive cells were admixed with the inflammatory infiltrates mostly along the
      intact limiting plate. They were also detected multifocally in a linear pattern
      along the dilated sinusoid. In chronic active hepatitis, very strong alpha-SMA
      staining was detected at the site of piecemeal necrosis and adjacent lobules. A
      SMA expression was decreased in some cases after interferon treatment. In cases
      of transplanted liver biopsies, expression of intralobular alpha-SMA was
      diffusely increased but showed no correlation with degree of acute rejection.
      Cirrhotic livers revealed strong alpha-SMA positivity in fibrous septae as well
      as in the perisinusoidal space of intact hepatocytes at the leading edge of
      fibrosis. Interlobular bile ducts were concentrically circumscribed by alpha-SMA
      positive cells in cases of intrahepatic cholelithiasis. In trabecular type
      hepatocellular carcinomas, most sinusoidal lining cells were positive for alpha
      SMA. Most intralobular alpha-SMA positive cells represent, if not all,
      perisinusoidal cells (PSCs) which are involved in intralobular fibrogenesis in
      various liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305145
TI  - Neuromuscular and hemodynamic effects of mivacurium and succinylcholine in adult
      patients during nitrous oxide-propofol-fentanyl anesthesia.
AB  - The neuromuscular and hem+odynamic effects of mivacurium 0.15 mg/kg and
      succinylcholine 1 mg/kg were compared in 26 adult patients (ASA I and II) during
      nitrous oxide-oxygen-propofol-fentanyl anesthesia. Neuromuscular block was
      monitored by recording the compound electromyogram of the hypothenar muscle
      resulting from supramaximal train-of-four stimuli applied to the ulnar nerve.
      Time to onset of over 95% block and duration to 25% recovery of control twitch
      after injection of mivacurium were significantly longer than for succinylcholine
      (201 +/- 37.6 vs 54 +/- 5.2 sec and 13.0 +/- 2.2 vs 8.4 +/- 2.1 min; mean +/-
      SD). Onset of mivacurium with priming technique was shortened (125 +/- 20.7 sec),
      but was also slower than that of succinylcholine. Although the recovery index
      during spontaneous recovery was significantly longer for mivacurium than for
      succinylcholine (6.9 +/- 1.3 vs 5.1 +/- 0.9 min), antagonism with neostigmine at
      25% recovery of twitch height sufficiently facilitated the recovery index of
      mivacurium (4.5 +/- 1.0 min) to a level similar to that of succinylcholine with
      no statistical difference. The hemodynamic effects of mivacurium were few as
      compared to those of succinylcholine. In conclusion, mivacurium is considered to
      have additional advantages for short procedures when succinylcholine is
      undesirable.

PMID- 8305146
TI  - Gonadoblastoma and dysgerminoma associated with 46,XY pure gonadal dysgenesis--a
      case report.
AB  - Gonadoblastoma and dysgerminoma developed in a 24-year-old phenotypic female
      patient with 46,XY pure gonadal dysgenesis. This patient presented with primary
      amenorrhea. Clinical characteristics showed a typical stigmata of gonadal
      dysgenesis: primary amenorrhea, sexual infantilism, a small uterus and bilateral
      streak gonads. A 46,XY karyotype was made by lymphocyte culture. The patient was
      counseled to undergo a prophylactic bilateral gonadectomy, but she refused. Three
      years and three months after the initial diagnosis she felt a growing pelvic
      mass. Bilateral gonadectomy and total hysterectomy were performed. Histological
      examination revealed gonadoblastoma and dysgerminoma on both gonads. After
      surgery the patient received radiation therapy and also was started on hormone
      replacement therapy. Two years and two months after treatment by surgery the
      patient is well and free of recurrence.

PMID- 8305147
TI  - A case of primary hepatic actinomycosis.
AB  - Actinomycosis is a chronic suppurative and granulomatous disease characterized
      histologically by sulfur granules with extensive necrosis, fibrosis and sinus
      formation. Depending on the site of primary infection, actinomycosis is generally
      classified as cervicofacial, thoracic and abdominal type. The liver is known to
      be the primary site of infection in 15% with abdominal actinomycosis. The authors
      have experienced a case of liver abscess in a 24-year-old male. The sono-guided
      aspiration biopsy revealed findings of infiltration of neutrophils and
      characteristics sulfur granules by light microscopy. This case was thought to
      represent an instance of liver actinomycosis. Although there have been a lot of
      reports on actinomycosis of the liver in other countries, only 3 cases were
      reported in Korea.

PMID- 8305148
TI  - Natural course of spontaneously reduced lumbo-sacral fracture-dislocation--a case
      report.
AB  - We present a case of lumbosacral fracture-dislocation, which was spontaneously
      reduced during radiological examination. Such rapid reduction is, however, not
      reliable for long-term stability. We would like to report this case briefly
      because spontaneous reduction of lumbosacral fracture-dislocation has not been
      reported previously.

PMID- 8305150
TI  - Healthcare alternatives.

PMID- 8305149
TI  - Sudden chest pain: where does it come from?

PMID- 8305151
TI  - Capitation and fee for service--can they co-exist in private practice?

PMID- 8305152
TI  - Should your practice be caught dead without a living trust?

PMID- 8305153
TI  - Capitation and fee-for-service can they co-exist in private practice?

PMID- 8305154
TI  - The unconscious airway--can you manage it?

PMID- 8305155
TI  - Non-competition covenants--enforceable or not?

PMID- 8305156
TI  - Patient reception, examination and treatment.

PMID- 8305157
TI  - Roentgen ray anomalies. Pseudo-lesion of the anterior mandible.

PMID- 8305158
TI  - Metabolic disorders and associated emergencies.

PMID- 8305159
TI  - Pharmacologic profiles of primary emergency drugs.

PMID- 8305160
TI  - Independent contractor--to be or not to be?

PMID- 8305161
TI  - Roentgen ray anomalies. The right-angle localization technique.

PMID- 8305162
TI  - The usefulness of the captopril test as a simultaneous screening for primary
      aldosteronism and renovascular hypertension.
AB  - The usefulness of the captopril test as a simultaneous screening method for
      primary aldosteronism (PA) and renovascular hypertension (RVH) was evaluated in
      111 patients with essential hypertension, and in 79 patients with secondary
      hypertension, which included 16 patients with PA and 18 with RVH. Plasma renin
      activity (PRA, ng/mL/h) and plasma aldosterone concentration (PAC, ng/dL) were
      determined before and 90 min after administration of 50 mg of captopril in the
      supine position on a normal NaCl diet. A cutoff point or a discriminant function
      in the screening was determined by discriminant analysis. A quadratic
      discriminant function of PRA and PAC after the captopril test identified patients
      with PA with a false negative rate of 6.3% (1/16), and a false positive rate of
      0.6% (1/174) which was significantly lower than that of 3.4% at the basal state
      (P < .05). In the screening for RVH, the criterion of a postcaptopril PRA of
      greater than 10.6 ng/mL/h had a false negative rate of 5.6% (1/18) and a false
      positive rate of 15.1% (26/172). This false positive rate was also significantly
      lower than that using a criterion for precaptopril PRA of 2.21 ng/mL/h (P < .05).
      Accordingly, the captopril test was a useful method in the simultaneous screening
      for PA and RVH, and it may be particularly applicable in specialized hypertension
      clinics.

PMID- 8305163
TI  - Left ventricular mass and geometry before and after etiologic treatment in
      renovascular hypertension, aldosterone-producing adenoma, and pheochromocytoma.
AB  - To study left ventricular (LV) geometry in secondary hypertension and its
      evolution following etiologic treatment, echocardiography was performed in a
      total of 73 patients: 40 patients with renovascular hypertension (RVH), 21 with
      aldosterone-producing adenoma (APA), and 12 with pheochromocytoma (PH). Repeat
      echocardiography was possible in 43 of these patients, 3-24 months following
      curative renal revascularization or adrenal surgery. Age, sex ratio, and initial
      drug treatment score were comparable in the three etiologic categories, but 24-h
      ambulatory blood pressure and LV mass index were significantly higher in APA and
      RVH than in PH. End-diastolic LV volume was significantly smaller in PH than in
      APA and RVH. After treatment, the greatest reduction in LV mass occurred in APA (
      18%, P < .05) and the lowest in PH (-5%, NS). Both patients with APA and those
      with PH exhibited a significant decrease in LV wall thickness, whereas LV
      diameter tended to decrease in APA patients and to increase in PH patients. No
      significant cardiac changes occurred in RVH patients after treatment. Although LV
      mass index and ambulatory blood pressure were correlated both before and after
      treatment, LV mass index changes did not correlate with changes in ambulatory
      blood pressure or with the known duration of hypertension. Systolic function was
      normal before and following etiologic treatment in the three categories. These
      findings suggest that, in addition to blood pressure, volume and/or humoral
      factors influence the pathogenesis of left ventricular hypertrophy and its
      reversibility.

PMID- 8305164
TI  - Renin, angiotensinogen, and kallikrein gene expression in two-kidney Goldblatt
      hypertensive rats.
AB  - An imbalance in the activity of the vasopressor renin-angiotensin and
      vasodepressor kallikrein-kinin systems may play an important role in the
      pathogenesis of hypertension after unilateral renal artery constriction. To test
      this hypothesis, we examined the expression of the renin, angiotensinogen (Ao),
      and tissue kallikrein genes 7 and 25 days after placement of a 0.25-mm clip on
      the left renal artery of rats. One week after clipping, renin mRNA levels were
      4.6-fold higher in the clipped and 50% lower in the nonclipped kidneys compared
      with kidneys from sham-operated rats. At 25 days, renin mRNA levels in the
      clipped kidneys were not different from sham kidneys, but were suppressed to
      almost undetectable levels in the nonclipped kidneys. Steady-state Ao mRNA levels
      in the clipped kidneys were not different from those of nonclipped or sham
      kidneys at either 7 or 25 days. However, at 25 days, Ao mRNA levels were lower in
      the liver (70%), left ventricle (55%), and aorta (45%) of clipped than sham
      operated rats. The expression of the renal kallikrein gene was unchanged at 7
      days and was suppressed by 50% at 25 days. These results are consistent with the
      notion that activation of the intrarenal renin-angiotensin system occurs during
      the initial phase of the two-kidney, one-clip hypertension model. The renal
      kallikrein gene, in marked contrast to renin, becomes downregulated in the
      chronic phase. The differential regulation of renin-angiotensin and kallikrein
      genes may be an important pathogenetic factor in renovascular
      hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305165
TI  - Effects of magnesium and nifedipine infusions on insulin action, substrate
      oxidation, and blood pressure in aged hypertensive patients.
AB  - Eight aged (70.1 +/- 2.1 years), nonobese (body mass index [BMI] = 26.3 +/- 0.4),
      hypertensive (systolic blood pressure [SBP] = 184 +/- 4.1; diastolic blood
      pressure [DBP] = 105 +/- 2.4 mm Hg) subjects underwent a euglycemic
      hyperinsulinemic (7.1 pmol/kg x min during 240 min) glucose clamp with four
      different infusions: a) 0.9% NaCl; b) 1.0 micrograms/kg x min nifedipine; c) 100
      mumol/min magnesium; d) 1.0 micrograms/kg x min nifedipine plus 100 mumol/min
      magnesium. All tests were performed in random order. Simultaneous D-3-H glucose
      infusion and indirect calorimetry allowed us to determine glucose turnover
      parameters and substrate oxidation. Insulin infusion per se stimulated
      erythrocyte magnesium (1.83 +/- 0.04 v 1.98 +/- 0.03 mmol/L, P < .03) and calcium
      (4.7 +/- 0.3 v 6.2 +/- 0.4 mumol/L, P < .02) accumulation, and enhanced total
      body glucose disposal oxidative and nonoxidative glucose metabolisms. Infusion of
      insulin and nifedipine v insulin alone reduced insulin-mediated increase in
      intracellular calcium (5.4 +/- 0.3 v 6.2 +/- 0.4 mumol/L, P < .02), but
      potentiated the insulin effect upon nonoxidative glucose (15.4 +/- 0.4 v 11.1 +/-
      0.3 mumol/kg lean body mass [LBM] x min, P < .03) metabolism.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8305166
TI  - Comparison of nitrendipine and cilazapril in patients with hypertension and non
      insulin-dependent diabetes mellitus.
AB  - The metabolic and cardiovascular effects of nitrendipine and cilazapril in
      patients who have elevated blood pressure and non-insulin-dependent diabetes
      mellitus (NIDDM) were compared. After at least 6 weeks of a washout period, 20
      NIDDM patients who had diastolic blood pressure in the range of 90-105 mm Hg
      received a single-blind placebo for 4 weeks and then were randomized to receive
      20 mg nitrendipine once daily and 5 mg cilazapril once daily each for 12 weeks
      according to a crossover, double-blind procedure. Nitrendipine and cilazapril
      reduced diastolic blood pressure levels 12% and 13%, left ventricular mass index
      (LVMI) levels 13% and 12%, and raised whole glucose disposal levels 18% and
      19.5%, respectively. Only nitrendipine reduced glucose-stimulated insulin levels.
      Nitrendipine is as effective as cilazapril in lowering diastolic blood pressure
      and LVMI levels and in increasing glucose disposal levels in these patients.

PMID- 8305167
TI  - Augmentation of the renal tubular dopaminergic activity by oral calcium
      supplementation in patients with essential hypertension.
AB  - We studied the effect of oral calcium supplementation on renal tubular
      dopaminergic activity in patients with mild to moderate essential hypertension.
      Fifteen patients aged 45 to 68 years (nine men and six women, mean age 59 +/- 7
      [SD]) participated in the study. We orally administered calcium (1.0 g per day
      for 1 week) during hospitalization. The change in 24-h blood pressure (BP),
      measured by ambulatory BP monitoring, and excretions of electrolytes and
      catecholamines were investigated before and after 1 week of oral calcium
      supplementation. The mean values of 24-h systolic and diastolic BP showed no
      significant changes by calcium loading. Daily urinary excretion of free dopamine,
      sodium clearance (CNa), fractional excretion of sodium (FENa), and urinary volume
      were significantly increased by oral calcium supplementation. Urinary excretions
      of epinephrine and norepinephrine and creatinine clearance showed no significant
      changes by oral calcium treatment. CNa and FENa showed significant correlations
      with urinary excretion of free dopamine. These results suggest that oral calcium
      supplementation induces natriuresis partly through augmentation of renal tubular
      dopaminergic activity.

PMID- 8305168
TI  - Increased platelet cytosolic calcium responses to low density lipoprotein in type
      II diabetes with and without hypertension.
AB  - Non-insulin dependent diabetes mellitus (NIDDM) and hypertension are common
      diseases which are independently associated with insulin
      resistance/hyperinsulinemia, dyslysidemia, abnormalities of platelet function,
      and accelerated atherogenesis. The interaction of these independent risk factors
      is poorly understood. Recently, low density lipoprotein (LDL) receptors have been
      described, in platelets, and LDL elevates [Ca2+]i in these cells. In this study
      we have evaluated platelet [Ca2+]i responsiveness to LDL and arginine vasopressin
      (AVP) in NIDDM patients with (n = 28) and without (n = 13) concomitant
      hypertension, as well as in normal nondiabetic controls (n = 13). Platelet
      [Ca2+]i concentration-response curves to LDL for both NIDDM and hypertensive
      NIDDM were shifted significantly to the left when compared to the normotensive,
      nondiabetic controls. By contrast, no differences were seen in [Ca2+]i responses
      to 10 mumol/L AVP among any of the groups. To determine the possible role of
      hyperinsulinemia in this accentuated [Ca2+]i response to LDL, we measured basal
      and LDL-stimulated [Ca2+]i in platelets of normal volunteers after insulin
      treatment (0-100 mU/mL for 30 and 90 min). Insulin did not alter baseline or LDL
      stimulated (150 mg/mL) platelet [Ca2+]i. Thus, an enhanced platelet [Ca2+]i
      response to LDL is characteristic of diabetes, independently of blood pressure.
      As such, it may also help to explain the enhanced platelet aggregation,
      endothelial dysfunction, and accelerated atherosclerosis of NIDDM.

PMID- 8305169
TI  - Effect of long-term administration of 1,25 (OH)2 vitamin D3 on blood pressure and
      resistance artery contractility in the spontaneously hypertensive rat.
AB  - The effect of long-term daily injection of 1,25 (OH)2 vitamin D3 on blood
      pressure and contractile force generation by subsequently isolated mesenteric
      resistance arteries was examined using the spontaneously hypertensive rat (SHR)
      model of genetic hypertension. Beginning at 6 weeks of age, male SHR were given
      daily intraperitoneal injections of vehicle, or 1,25 (OH)2 vitamin D3 at 20, 30,
      or 40 ng/100 g body weight. Body weight and systolic blood pressure were
      determined weekly. After 9 weeks, serum was prepared for electrolyte analysis and
      mesenteric resistance arteries were isolated for assessment of contractile
      function using a wire myograph. Blood pressure became elevated in the rats
      receiving 20 and 40 ng 1,25 (OH)2 vitamin D3 after 5 weeks and remained elevated
      in the 40 ng group during the sixth week. Between weeks six to nine, blood
      pressure continued to rise but was not different among the groups. In addition,
      during the period between 6 and 9 weeks, there was a decline in the rate of
      weight gain in rats receiving 30 and 40 ng 1,25 (OH)2 vitamin D3. Serum ionized
      Ca2+ was significantly elevated in the three groups treated with 1,25 (OH)2
      vitamin D3 compared with control. The active stress response of resistance
      arteries to norepinephrine and arginine vasopressin was significantly elevated in
      rats that received 30 and 40 ng 1,25 (OH)2 vitamin D3, but no differences in
      apparent sensitivity to these agonists were detected.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8305170
TI  - Quinapril prevents stroke both during and after the treatment period in stroke
      prone spontaneously hypertensive rats.
AB  - The effects of long-term oral administration of quinapril on the occurrence of
      stroke and on mortality were investigated in young salt-loaded stroke-prone
      spontaneously hypertensive rats (SHR-SPs) during the treatment period (8th-34th
      week of age) and up to 6 weeks thereafter. Simultaneously, blood pressure, saline
      intake, diuresis, and proteinuria were investigated at regular intervals, and
      cerebrovascular, renal, and cardiac lesions were assessed after death. Untreated
      SHR-SPs served as controls. Quinapril completely suppressed stroke and mortality,
      afforded only limited protection v blood pressure rise, and prevented any
      increase in saline intake, diuresis, and proteinuria both during and after the
      treatment period. Quinapril long-lastingly prevented vascular fibrinoid necrosis
      development at the cerebral, but also at the renal and cardiac levels. In the
      kidneys, vascular intimal and medial hyperplasia were strongly reduced, as were
      the glomerular and tubulo-interstitial lesions. At the cardiac level, intimal and
      medial hyperplasia were slightly reduced but infarction and fibrosis were hardly
      affected. As the renin-angiotensin system is highly stimulated in SHR-SPs and as
      angiotensin II (AII) is responsible for fibrinoid necrosis formation, vessel
      obstruction, and stroke in these animals, we conclude that the long-lasting
      protection afforded by quinapril v stroke and mortality in SHR-SPs both during
      and after the treatment period is mostly due to the drug-induced interruption of
      the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305172
TI  - Ambulatory blood pressure patterns in youth.
AB  - We examined the influence of sex, race, and age on ambulatory blood pressure (BP)
      patterns in youths. The subjects were 300 normotensive, healthy adolescents
      between the ages of 10 and 18 years, including 160 boys and 140 girls, of whom
      149 were white and 151 were black. The data were divided into periods of activity
      (Period I: 8 AM to 10 PM) and inactivity (Period II: 10 PM to 8 AM). Boys had
      higher systolic BP during both Period I (117 +/- 11 nu 112 +/- 8 mm Hg; P < .05)
      and Period II (109 +/- 11 nu 106 +/- 10 mm Hg; P < .03). Blacks had higher
      systolic (108 +/- 10 nu 106 +/- 10 mm Hg; P < .01) and diastolic BP (63 +/- 8 nu
      60 +/- 7 mm Hg; P < .003) during Period II. Interactions between race and age
      were found for both systolic (P < .005) and diastolic (P < .005) BP during Period
      II. Further analyses indicated associations between age and both systolic (beta =
      1.16; P < .001) and diastolic (beta = 1.04; P < .0001) BP in black but not white
      subjects. An interaction was observed between sex and age for systolic BP during
      Period II (P < .005), with a relationship for boys (beta = 1.47; P < .001) but
      not for girls. These results suggest that the black adolescents showed a
      progressive increase in nocturnal BP with age, a pattern not observed in the
      white youths. This increased BP load may contribute to the early development of
      hypertension and BP-induced target organ damage in blacks.

PMID- 8305171
TI  - Chronic pressure-natriuresis relationship in dogs with inherited essential
      hypertension.
AB  - A genetic model of essential hypertension in the dog was studied to describe the
      phenotypic expression of the arterial pressure, as well as to determine the
      relationship between mean arterial blood pressure (MAP), hormone, and renal
      excretory responses to four different levels of sodium intake (5, 40, 120, 240
      mEq/day) delivered intravenously and isotonically. This model was developed at
      the University of Pennsylvania (U/Penn) and termed Pennsylvania hypertensive dogs
      (PHD). The MAP was recorded beat-by-beat, 24 h/day, in 16 dogs. Water and sodium
      balances were determined daily for 4 days at each level of intake and blood
      samples were collected on the last day of each salt step for analysis of plasma
      renin activity (PRA), atrial natriuretic peptide (ANP), aldosterone (ALDO), and
      vasopressin (AVP). After the study, the dogs were designated as hypertensive (PHD
      HT) when the 24-h average MAP was greater than 110 mm Hg and systolic pressure
      was greater than 160 mm Hg. Dogs that failed to meet both criteria were
      designated as normotensive genetic controls (PHD-NT). Although sodium was
      retained during the first day of each increase of salt intake in both groups, a
      return to balance was observed within the 4 days. There was no apparent change in
      the slope of the chronic renal function curve in either group of PHD studied,
      although the PHD-HT exhibit a curve shifted to a higher level of MAP. Plasma
      hormone levels in both groups of PHD studied responded in a manner similar to
      normal mongrel dogs with reductions of PRA, ALDO, elevations of ANP, and no
      change in AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305173
TI  - International roundtable discussion of national guidelines for the detection,
      evaluation, and treatment of hypertension.

PMID- 8305174
TI  - The posterior tibial muscle explored? Answer--hardly ever!

PMID- 8305175
TI  - Use of goal attainment scaling in brain injury in a rehabilitation hospital.
AB  - We report a study of the measurement properties of goal attainment (GA) scaling
      when used in the rehabilitation of brain injury patients. GA scaling is an
      individualized measurement technique with mathematical properties allowing for
      calculation of summary scores with a normal distribution. The present study
      examined 16 inpatients, 13 of whom had suffered a traumatic brain injury. In
      addition to GA scaling, standardized measures were employed to address issues
      such as content validity and construct validity. GA scaling change scores
      correlated highly (r = 0.81) with clinical judgment of efficacy and modestly with
      standard performance measures. A high level of inter-rater reliability was found
      between admission (r = 0.92) and discharge (r = 0.94) scores. GA scaling seems to
      be a feasible method of evaluating rehabilitation in brain injury patients, with
      promising measurement properties. The goals set are extremely meaningful to the
      patient and rehabilitation team, providing valuable feedback throughout the
      rehabilitation course.

PMID- 8305176
TI  - Electrodiagnosis of upper limb weakness in acute quadriplegia.
AB  - Clinical and neuropathologic observations after cervical spinal cord injury
      suggest varying involvement of gray and white matter. The resulting upper limb
      weakness may reflect varying degrees of upper motoneuron (UMN) and/or lower
      motoneuron (LMN) involvement. This study uses electrophysiologic measures,
      including compound muscle action potential (M response) amplitude, root mean
      square (RMS) of the surface electromyographic activity during voluntary muscle
      contractions and the firing rate of motor units, to distinguish UMN and LMN
      weakness in upper extremities after acute quadriplegia. M response amplitude did
      not correlate with strength; many muscles had large M responses given their
      strength. These muscles manifest: (1) high M/RMS ratios (ratio of electrically
      elicited to voluntarily recruited electromyographic activity) and (2) slow firing
      rates of single motor units during maximal isometric contractions. For muscles
      with normal M amplitudes, M/RMS ratio correlates inversely with strength. For
      muscles with normal M/RMS ratios, M amplitude correlates positively with
      strength. Cluster analysis was used to distinguish UMN, LMN or Mixed types of
      weakness. Distinguishing these different types of weakness in acute quadriplegia
      may allow individualized rehabilitation for the type of weakness present.

PMID- 8305177
TI  - Quantification of attention-related behaviors in individuals with traumatic brain
      injury. A pilot study.
AB  - Clinical disorders of attention are common after traumatic brain injury but
      objective measures of their nature and severity are lacking. We developed a
      standardized independent work task to be performed by patients in a controlled,
      distracting environment. Videotaped records of patient behavior were made and
      coded in 15-s intervals for on-task behavior, presence of distractors and
      presence of extraneous motor behavior. Interrater reliability was good to
      excellent across eleven testing sessions involving four patients. This evaluation
      system revealed clinically important differences in on-task behavior among the
      four patients, as well as different levels of distraction in response to external
      stimuli. It also showed effects of different tasks and repeated sessions. These
      data indicate that this evaluation system and accompanying coding process are
      reliable and provide preliminary evidence that they produce clinically valid
      results.

PMID- 8305178
TI  - Coping with the late effects: differences between depressed and nondepressed
      polio survivors.
AB  - This study examined differences between depressed and nondepressed individuals
      with a history of paralytic poliomyelitis in terms of demographics, health status
      and coping strategies. The prevalence of distress and depression in this group of
      116 polio survivors was determined. Subjects completed the Brief Symptom
      Inventory, the Coping with Disability Inventory and a questionnaire concerning
      their polio histories and self-perceptions of health. Medical assessments were
      performed by physicians. Only 15.8% of the sample had scores indicating
      depression and elevated distress. Depressed/distressed polio survivors were more
      likely to: be living alone, be experiencing further health status deterioration,
      seek professional help, view their health as poor, report greater pain, be less
      satisfied with their occupational status and their lives in general and exhibit
      poorer coping outcome behaviors in relation to their disability. Three factors in
      coping with the late effects of polio were identified through a factor analysis
      of the Coping with Disability Inventory: positive self-acceptance, information
      seeking/sharing about the disability and social activism. Differences between
      depressed/distressed and other polio survivors were found across these three
      factors, with depressed/distressed subjects having significantly lower coping
      scores. These and other results are discussed.

PMID- 8305180
TI  - The "value" of functional independence measure scores.
AB  - Functional independence measure (FIM) scores are frequently used as if the
      various sections are of equal importance and as if the interval between each
      score is equal. We tested this hypothesis by using marketing research techniques
      to assess the value to rehabilitation nurses and therapists of four of the six
      sections. Communication was valued more highly than continence, mobility and self
      care in that order. The interval between the scores is not equal, with difference
      between a FIM 2 and 3 being greater than between a FIM 5 and 6. However, when the
      other difficulties such as interexaminer reliability are considered, these score
      differences are not great. We concluded that for practical purposes FIM scores
      may be used as if they were of equal interval spacing, and the scores of the
      various sections may be added together.

PMID- 8305179
TI  - The vestibulo-ocular reflex and dysequilibrium after hemispheric stroke.
AB  - Patients with hemispheric lesions frequently suffer from equilibrium impairment
      that may be prolonged and may interfere with rehabilitation. In an effort to
      clarify whether this phenomenon is related to vestibular dysfunction, we examined
      the relationship of the horizontal vestibulo-ocular reflex (VOR) with stability
      in 15 patients with unilateral hemispheric stroke. The study included electro
      oculographic recording of the VOR while the patients were rotated in a vestibular
      chair. Stability was scored in accordance with the patients' ability to maintain
      equilibrium in six graded positions. The findings demonstrated relationship
      between VOR gain (eye/head displacement) and equilibrium. It is suggested that
      the "loss of balance" after stroke may be related to an impairment of the
      corticovestibular modulation of the vestibular function.

PMID- 8305181
TI  - Strategic-behavioral intervention in the treatment of chronic nonorganic motor
      disorders.
AB  - Chronic nonorganic motor disorders pose particular difficulties because of a
      combination of diagnostic confusion and intractability to psychotherapeutic or
      behavioral interventions. Three cases are presented, all of whom failed a
      rehabilitation approach that emphasized basic behavioral principles of shaping
      and reinforcement. Despite this initial failure, all three patients showed
      dramatic and rapid improvement after implementation of an intervention combing
      elements of strategic and behavior therapy. The strategic element consisted of
      placing patients in a double bind by telling them full recovery constituted proof
      of an organic etiology and failure to recovery constituted conclusive evidence of
      a nonorganic or psychiatric etiology. These cases also illustrate the difficulty
      in distinguishing between conversion and factitious disorders.

PMID- 8305183
TI  - Priorities and rehabilitation research. Commentary.

PMID- 8305182
TI  - The Uniform Data System for Medical Rehabilitation report of first admissions for
      1992.

PMID- 8305184
TI  - Physical medicine and rehabilitation as a primary care specialty. Commentary.

PMID- 8305185
TI  - Quality-adjusted life years and the ethical values of health care.
AB  - This paper defines the QALY, the quality-adjusted life year, and examines the
      ethical dimensions of its potential uses in health care, with special reference
      to rehabilitation. The implications of QALYs are analyzed with respect to three
      central ethical values in health care: freedom, happiness and fairness. QALYs may
      be useful in expanding patient freedom and in securing greater social happiness
      in the allocation of resources. However, QALYs raise important problems of
      fairness and have a bias toward curative interventions.

PMID- 8305186
TI  - Assessing academic productivity.

PMID- 8305187
TI  - Depression in Alzheimer patients: discrepancies between patient and caregiver
      reports.
AB  - Estimates of the prevalence of depression in dementia patients vary widely. One
      problem in accurate identification of such depression is determining whether to
      rely on demented patients' reports or second-party caregivers' reports of
      symptoms. To further explore this problem, 31 outpatients with probable Alzheimer
      disease and their 31 caregivers were interviewed separately with depressive
      symptom questionnaires. Caregivers reported more depressive symptoms in dementia
      patients than patients reported for themselves. Correlations between caregivers'
      and patients' reports of individual symptoms ranged between -0.23 to 0.76, with
      lowest correlations found for intrapsychic distress, cognitive impairment, and
      hallucinations. Patients' responses were not necessarily affected by stereotypic
      responding or severity of impairment, but patients appeared to under-report
      symptomatology. Caregivers' responses were associated with the extent of contact
      with the patients, familial relationship, and sources of information used to
      determine patients' mood but were not correlated with caregivers' depression or
      ratings of how they would feel if they were "in the patient's shoes."

PMID- 8305188
TI  - Alternative calculation of the global clinical dementia rating.
AB  - The Clinical Dementia Rating (CDR) is a widely used instrument for rating the
      global severity of dementia, with scores in six independently rated categories
      used as a basis for computing a global score. We have found that the algorithms
      currently used to calculate the global score from the six component scores
      produce results that are sometimes inconsistent with the goals of the rating
      scale. We systematically analyzed these incongruities and developed an
      alternative algorithm that eliminates them while retaining the fundamental
      features of the original method.

PMID- 8305189
TI  - Comparison of the severity of neuropathologic changes in familial and sporadic
      Alzheimer's disease.
AB  - We compared the density of neurofibrillary tangles (NT) and neuritic (senile)
      plaques (NP) in 10 cortical areas, the amygdala, the hippocampus, the
      parahippocampal gyrus, and the cerebellum in patients with familial (FAD) and
      sporadic (SAD) Alzheimer's disease with early (< 55 years), intermediate (55-70
      years) and late (> 70 years) ages of onset of dementia and age-matched controls.
      From a total of 199 cases of pathologically confirmed AD in our laboratory, 60
      cases with appropriate brain sections and information as to family history, age
      of onset, duration of dementia, and brain weight were available for
      semiquantitative analysis of the frequency of NT and NP utilizing the Consortium
      to Establish a Registry for Alzheimer's Disease protocol. There were 28 SAD and
      32 FAD (including seven Volga Germans) cases and 16 age-matched controls. In all
      brain regions, cases had more severe changes than controls (p < 0.001). Brain
      weight correlated inversely with duration of disease (p < 0.001). No significant
      differences were found in the severity scores of NT and NP between FAD and SAD.
      There was an inverse correlation between age of onset of dementia and the density
      of NT and NP in all regions in FAD and SAD combined. P values for NT were in the
      frontal (superior-middle and orbital, p < 0.0005; gyrus rectus, p = 0.0029),
      parietal (p = 0.0007), and medial occipital cortex (areas 17 and 18, p < 0.01),
      and for NP were in the superior temporal gyrus (p = 0.0085) and area 17 (p =
      0.0003), and age of onset of dementia. In summary, using these criteria we found
      no compelling evidence that the neuropathologic characteristics of FAD are
      different from those of SAD.

PMID- 8305190
TI  - Longitudinal effects of Alzheimer disease on discourse production.
AB  - As part of a 5-year study of the longitudinal effects of Alzheimer disease (AD)
      on language, discourse samples from three patients diagnosed with AD and three
      matched normal controls were analyzed. A picture-description task was used to
      elicit comparable samples of discourse. Subjects were asked to describe the
      "Easter Morning" picture by Norman Rockwell. Samples were tape recorded,
      transcribed, and scored using eight measures of discourse production. These
      measures successfully quantified the changes in quantity and quality observed in
      the discourse of AD patients over time. Results revealed remarkably similar
      patterns, adding a longitudinal dimension to the growing body of knowledge of the
      effects of AD on discourse production.

PMID- 8305191
TI  - Primary aortoduodenal fistula caused by severe atherosclerosis, not by aneurysm.
AB  - Primary aortoduodenal fistula is an uncommon cause of massive upper
      gastrointestinal hemorrhage usually due to pressure erosion of an abdominal
      aortic aneurysm into the third portion of the duodenum. This report describes a
      case of a 59-year-old man who died of massive gastrointestinal hemorrhage due to
      a primary aortoduodenal fistula. This case is unique in that the fistula formed
      as a result of complex atherosclerotic disease of the abdominal aorta, with
      adventitial chronic inflammation and foreign body reaction against atheromatous
      plaque, and not from an aneurysm. We were unable to identify any other reports of
      aortoduodenal fistulas developing spontaneously in the absence of aneurysmal
      disease of the aorta.

PMID- 8305192
TI  - Mitral valve anomalies associated with Ebstein's malformation of the tricuspid
      valve.
AB  - The original description of Ebstein's anomaly mentioned a mild deformity of the
      mitral valve. Reviews of large series of cases with Ebstein's malformation have,
      however, tended to omit reference to accompanying mitral valve malformations. We
      have compared the mitral valves in 19 specimens with Ebstein's malformation with
      those in 30 age-matched controls in order to determine the prevalence and nature
      of these anomalies. In the Ebstein's group the mitral valve was abnormal in 14
      hearts with orificial anomalies in four, leaflet anomalies in 11, cord anomalies
      in 11 and papillary muscle anomalies in 13. In the control group, five cases
      showed mild shortening of the tendinous cords. Half of the changes found in the
      Ebstein's group were of moderate or significant degree suggesting a primary
      involvement of the mitral valve. In time, dynamic alterations within the left
      ventricle might become superimposed and contribute to the development of
      clinically significant lesions.

PMID- 8305193
TI  - Pathological sequelae of implantation of intracorporeal left ventricular assist
      devices in the calf.
AB  - Thromboembolic complications have previously been a major pathological
      complication of left ventricular assist device (LVAD) insertion and appear to be
      a consequence of the use of smooth polyurethane linings. Textured biomaterial
      surfaces are designed to attract a stable coagulum which becomes organized to
      form a neointima. We describe the pathological changes following experimental
      implantation of textured-surface LVADs in calves. The incidence of systemic
      embolization from such linings appears to be low. Surface modifications with cell
      seeding offer the possibility of further reduction in incidence of this problem.
      However, degradation of prosthetic valves may be a potential source of emboli and
      infection. With these complications minimized, the most significant pathological
      changes observed appear to relate to the device haemodynamics. At present
      renovascular changes associated with systemic hypertension appear to be the
      greatest potential problem for the long-term use of these devices.

PMID- 8305194
TI  - The lining of textured surfaces in implantable left ventricular assist devices.
      An immunocytochemical and electronmicroscopic study.
AB  - OBJECTIVE: The aim was to examine and identify some components of biological
      linings developed upon the textured surfaces of a circulatory assist device. The
      development of biological linings upon a textured surface circulatory assist
      device was evaluated in patients implanted for periods ranging from 84 to 132
      days. METHODS: Explanted devices were examined macroscopically. Light microscopy,
      transmission electron microscopy and immunocytochemistry techniques were employed
      to evaluate the histogenesis of the tissue deposits upon the device surfaces.
      Visible material was essentially limited to focal areas upon the static housing
      and the periphery of the pusher-plate diaphragm (Biomer). RESULTS: Microscopy of
      the linings showed fibrin-rich areas with platelets, monocytes and few spindle
      shaped surface cells. Central areas were composed of multiple layers of spindle
      shaped cells separated, mainly, by collagen. Giant-cell foreign-body reaction to
      Biomer fibrils was seen. CONCLUSION: Transmission electron microscopy and
      immunocytochemistry indicated the presence of at least two cell populations:
      fibroblasts and smooth muscle-like cells, or 'myofibroblasts'. There was no
      evidence of endothelial cell presence.

PMID- 8305195
TI  - Xanthine oxidase/dehydrogenase release following ischemia in isolated rat hearts.
AB  - The release of xanthine oxidase/dehydrogenase XO/XDH (4.99 +/- 1.08 x 10(-12)
      moles/min/g wet wt in aerobic hearts) was not significantly increased following
      30 min of ischemia, but almost doubled following 45 min of ischemia, indicating
      some endothelial cell damage. This release, however, was small compared to the
      release induced by digitonin perfusion (26 fold increase in an equivalent volume
      of effluent) and was nearly 1000 fold less than the enzyme activity measured in
      the tissue homogenate. There was a significant decrease in cardiac function
      (heart rate and systolic pressure) following 30 min of ischemia and no recovery
      of function following 45 min of ischemia and reperfusion. Endothelial cell damage
      determined by XO/XDH release is negligible during times of ischemia that cause
      severe damage to myocardial contractility. Coronary endothelial cells should not
      contribute significantly to circulating XO/XDH levels following ischemia.

PMID- 8305196
TI  - Interstitial myocardial neutrophil accumulation between 3 and 72 h of reperfusion
      does not significantly affect infarct size in porcine hearts.
AB  - The inflammatory response--mediated by activated neutrophils--is assumed to play
      an important role in the pathogenesis of reperfusion injury. This study
      investigated whether extravascular myocardial neutrophil accumulation between 3
      and 72 h of reperfusion affects infarct size in porcine hearts. The left anterior
      descending coronary artery was ligated distally in 24 pigs for 45 min and
      reperfused for 3 h (n = 8), 24 h (n = 8), or 72 h (n = 8). Infarct size and
      extravascular myocardial accumulation of neutrophils was evaluated at the end of
      the experiments. Global hemodynamic characteristics were comparable for the three
      groups both before and during ischemia. Neutrophil count/mm2 reperfused
      myocardium increased substantially from 4 +/- 2 (3 h of reperfusion) to 129 +/-
      70 (24 h of reperfusion, p < 0.001). After 3 d of reperfusion, the neutrophil
      count had decreased to 10 +/- 7. The invasion of neutrophils between 3 and 24 h
      of reperfusion did not significantly affect the extent of myocardial necrosis.
      Infarct sizes after 3 h (62.6 +/- 20%), 24 h (71.8 +/- 13%), and 72 h of
      reperfusion (67.6 +/- 18%) did not differ significantly. This finding does not
      suggest that a significant amount of myocytes are destroyed by extravasated
      neutrophils between 3 and 72 h of reperfusion.

PMID- 8305197
TI  - Enhancement of myocardial damage and alteration of lymphocyte subsets in murine
      model of postpartum myocarditis.
AB  - Acute viral myocarditis is considered to be one of the pathogenetic mechanisms
      for postpartum cardiomyopathy. In this study we examined the severity of viral
      myocarditis in postpartum mice infected 24 h after delivery. Although there were
      no differences in survival rate between postpartum mice and nonpregnant infected
      mice (control), the severities of myocardial damage in the postpartum mice was
      significantly greater than that in control mice (area of cell infiltration; 12.9
      +/- 3.8 vs. 7.3 +/- 4.0%, p < 0.05 and necrosis; 49.7 +/- 10.9 vs. 30.2 +/- 7.1%,
      p < 0.05), and the dilatation of left ventricle was more prominent in postpartum
      mice both on acute and subacute phases. These results show that myocardial damage
      due to viral infection is enhanced in postpartum state when infected soon after
      delivery. Moreover the histopathological features of the myocarditis in the
      subacute phase is similar to that seen with dilated cardiomyopathy. Although
      there was no change in T cell subsets of peripheral blood between two groups, the
      percentages of L3T4+ (helper/inducer) cells and asialo GM1+ (NK) cells in the
      heart were statistically greater in postpartum mice than in control mice (L3T4+
      cells; 8.7 +/- 0.4 vs. 6.1 +/- 2.0, p < 0.05 and asialo GM1+ cells; 7.8 +/- 0.9
      vs. 5.8 +/- 0.9, p < 0.05). However, this increase was obviously smaller than
      amount of the percentage of Lyt2+ (suppressor/inducer) cells. Thus, it is unclear
      whether this change of T cell subsets is associated with the development of
      myocarditis.

PMID- 8305199
TI  - Diastolic dysfunction of stunned myocardium.
AB  - The prolonged regional contractile failure of reperfused myocardium has usually
      been characterized in terms of systolic function, while only few reports on its
      diastolic function are available. None of these studies considered changes in the
      isovolumic diastole and the subsequent filling phase separately. Therefore, in
      the present study, the velocities of wall excursion during systole (Vsys),
      isovolumic diastole (Viso) and filling phase (Vfill) were determined in 12
      anesthetized dogs. Additionally, post-ejection thickening (Pejt), a marker of
      left ventricular asynchrony, was determined. Measurements were performed under
      control conditions, during a 15 minute left circumflex (LCX) coronary artery
      occlusion (CAO) and at 10 minutes, 4 and 8 hours reperfusion. Heart rate, left
      ventricular pressure, and Vsys, Viso, Vfill, and Pejt of the anterior myocardium
      remained unchanged throughout the experiments. During CAO, systolic wall
      thickening of the posterior wall was reversed to systolic wall-thinning. Upon
      reperfusion, Vsys started to recover (2.5 +/- 3.2 mm/s at 10 minutes) and
      gradually improved over 8 hours of reperfusion (4.6 +/- 3.2 mm/s at 4 hours, 6.4
      +/- 1.5 mm/s at 8 hours). Viso became positive during CAO (9.4 +/- 7.1 mm/s vs. 
      5.6 +/- 3.9 mm/s under control conditions) and was unchanged at 10 minutes
      reperfusion (7.9 +/- 5.2 mm/s). After 4 hours and 8 hours of reperfusion, Viso
      recovered to 1.2 +/- 9.2 mm/s and -0.3 +/- 10.7 mm/s, respectively. Vfill also
      became positive during CAO (1.5 +/- 6.2 mm/s vs. -18 +/- 8.7 mm/s under control
      conditions). There was a quick recovery of Vfill (-9.4 +/- 7.5 mm/s) with the
      onset of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305198
TI  - Determination of regional myocardial blood flow using fluorescent microspheres.
AB  - Determination of blood flow in tissues at risk for infarction is necessary for in
      vivo studies of the pathologic effects of vascular occlusion. Such blood flow
      measurements are traditionally carried out using radioactive microspheres. These
      are expensive and may pose a significant hazard to laboratory personnel. In
      addition, disposal of radioactive wastes, especially radioactive carcasses, is an
      increasingly expensive and inconvenient process. To avoid these problems, we have
      developed a modified procedure using fluorescent microspheres. To measure blood
      flow, spheres are injected intravenously and a blood sample is taken. Following
      cardiectomy, appropriate segments of left ventricular myocardium are digested
      with proteases to release the spheres, which are then purified through sucrose
      gradients. The spheres may be counted manually using an epifluorescence
      microscope, or by flow cytometry. Comparison of this method with the traditional
      radioactive microsphere procedure reveals similar results for the two methods.
      Fluorescent microspheres should provide a useful and accurate alternative method
      for measuring blood flow in studies of vascular disease.

PMID- 8305200
TI  - Isolated right-sided endocarditis in Hong Kong Chinese.
AB  - Thirteen histologically-proven cases of endocarditis confined to the right side
      of the heart were found in 9406 consecutive autopsies. Eleven cases involved the
      tricuspid valve and two the atrial endocardium. Nine cases were in males and 4 in
      females. Only one case showed underlying valvular/endocardial disease. Eight
      cases were infective, with Staphylococcus aureus being the predominant organism,
      and 5 non-infective. For the infective cases, intravenous drug abuse was the
      commonest predisposing factor, and malignancy the commonest association for the
      non-infective. The commonest overall complication was lung abscess due to septic
      emboli in the 3 drug addicts, a common association in other reported series.
      These latter cases are particularly important to recognize, being generally more
      responsive to treatment than left-sided infective endocarditis.

PMID- 8305201
TI  - Lipomatous hamartoma of the interatrial septum.
AB  - Four cases of lipomatous hamartoma of the interatrial septum (LHIAS) were
      diagnosed at autopsy, three in elderly women, two of whom were morbidly obese.
      One patient had signs of congestive cardiac failure, without other significant
      cardiopulmonary disease, which was thought to be a result of the interatrial
      lipomatous hamartoma, while in the others, the LHIAS was considered an incidental
      finding. This condition, previously considered a hypertrophic phenomenon, is now
      best described as hamartomatous, and is being recognized more frequently both by
      clinicians and pathologists.

PMID- 8305202
TI  - Sequence, expression, and chromosomal assignment of a human sperm outer dense
      fiber gene.
AB  - Outer dense fibers (ODFs) are located on the outside of the axoneme in the
      midpiece and principal piece of the mammalian sperm tail and may help to maintain
      the passive elastic structures and elastic recoil of the sperm tail. We have
      identified and describe here a human gene that is homologous to the Mst(3)CGP
      gene family of Drosophila melanogaster and encodes an ODF protein of 241 amino
      acids. The transcribed region has a size of approximately 1 kb and contains two
      exons of 416 bp and 406 bp, respectively, not including the 3' untranslated
      region. The gene is expressed in testis but not in human spleen, kidney, or brain
      and resembles in this respect the expression of the Drosophila Mst(3)CGP gene
      family in the male germline. An antiserum raised against a synthetic peptide
      derived from the N-terminus of the encoded sequence identified a protein of
      approximately 32 kDa in an extract of human sperm flagella. By Southern-blot
      analyses and in situ hybridization, the ODF gene was localized to band q22 of
      chromosome 8. The isolation of a human gene encoding a sperm tail protein may
      provide the ability to identify and investigate, on the molecular level, possible
      reasons for human male infertility that are dependent on flagellar disturbances.

PMID- 8305203
TI  - Zinc, iron, and copper contents of Xenopus laevis oocytes and embryos.
AB  - Zinc is essential for vertebrate development; its deficiency results in multiple
      congenital malformations. Knowledge of the zinc biochemistry that underlies
      embryologic development is very limited. This has led us to investigate the zinc,
      iron, and copper contents of Xenopus laevis oocytes and embryos. Stage 1-6
      oocytes, isolated from ovaries, and stage 1-40 embryos, obtained by in vitro
      fertilization techniques, were washed in metal-free water prior to digestion by
      70% ultrapure HNO3. The metal content of the digests was analyzed by atomic
      absorption spectrometry. Stage 6 oocytes contain 65.8 +/- 4, 31.1 +/- 3, and 0.68
      +/- 0.2 ng of zinc, iron and copper, respectively. The corresponding
      concentrations are 1, 0.5, and 0.01 mM in 1 microliter eggs. The metal content
      varies as a function of egg maturation. The zinc content increases from 3-7 to >
      60 ng by stages 3 and 6, respectively. A similar pattern is noted for iron, which
      increases from 2-5 to 30 ng at analogous stages. In contrast, the copper content
      remains virtually unchanged in oocytes undergoing maturation. Importantly, the
      total of all three metals does not vary throughout the first 50 stages of
      development, when all tadpole organs are forming. Hence, the full complement of
      zinc, iron, and copper needed for incorporation into apoproteins during
      development is already present at a time when oocyte maturation is completed. The
      specific metalloproteins that store, donate, and accept these metals during
      induction and organogenesis and the alterations caused by metal deficiency can
      now be identified.

PMID- 8305204
TI  - Derivation and characterization of putative pluripotential embryonic stem cells
      from preimplantation rabbit embryos.
AB  - We have derived putative embryonic stem (ES) cell lines from preimplantation
      rabbit embryos and report here their initial characterization. Two principal cell
      types emerged following serial passage of explanted embryos, and each has
      subsequently given rise to immortalized cell lines. One cell type has morphology
      identical to primary outgrowths of trophectoderm, is strictly feeder-cell
      dependent, and spontaneously forms trophectodermal vesicles at high cell density.
      The second type appears to represent pluripotent ES cells derived from the inner
      cell mass as evidenced by 1) ability to grow in an undifferentiated state on
      feeder layers, 2) maintenance of a predominantly normal karyotype through serial
      passage (over 1 year), and 3) ability to form embryoid bodies, which form
      terminally differentiated cell types representative of ectoderm, mesoderm, and
      endoderm. These ES cells may ultimately be suitable for introduction of germline
      mutations (via homologous recombination). The rabbit's size, reproductive
      capability, and well-characterized physiology make it suitable for a wide range
      of investigations, particularly for development of large animal models of human
      disease.

PMID- 8305205
TI  - Relationships between the completion of first cleavage and the chromosomal
      complement, sex, and developmental rates of bovine embryos generated in vitro.
AB  - One thousand eighty-four two-cell bovine embryos produced from 1,574 oocytes
      matured and fertilized in vitro were cultured as groups separated according to
      the time when they completed their first cleavage (24, 30, 40, 48, or 62 hr
      postinsemination; hpi). At 5 days after insemination, the proportions of each
      group that had progressed to the eight-cell stage or beyond were determined and
      the 350 that had done so were fixed and examined cytogenetically for cell number,
      chromosomal abnormalities, and sex. Embryos in the "early" cleaving (24 and 30
      hpi) and "late" cleaving (40-62 hpi) groups were compared. Early cleaving embryos
      were more likely to have developed to the eight-cell stage or beyond (52.2% vs.
      20%), contained more cells (22 vs. 17), and were more likely to be male (3.6:1
      vs. 0.93:1). It is suggested that these phenotypic differences between the sexes
      begin before the embryonic genome is generally thought to become activated and
      are due either to differential processing of X- and Y-bearing sperm within the
      zygote or to very early differential expression of genes derived from X- and Y
      bearing sperm.

PMID- 8305207
TI  - Video microscopic analysis of ionophore induced acrosome reactions of lobster
      (Homarus americanus) sperm.
AB  - Sperm from the American lobster (Homarus americanus) are normally nonmotile.
      However, during fertilization, the sperm undergo a calcium-dependent acrosome
      reaction that propels them forward about 18 microns. The reaction occurs in two
      phases, eversion and ejection, which take place too quickly to permit analysis by
      direct observation. The purposes of this study were to examine the structural
      changes occurring in sperm during the normal acrosome reaction and to determine
      the rate of the reaction using video microscopy. The reaction was induced in
      vitro by ionophore A23187 and recorded using a video system attached to a Nikon
      Nomarski interference microscope. Videotapes were played back frame by frame (30
      frames/sec), and images of reactions from 10 sperm were analyzed. The acrosome
      reaction, including the eversion of the acrosomal vesicle and ejection of the
      subacrosomal material and nucleus, can be divided into 4 steps: (1) expansion of
      the apical cap followed by expansion of the remainder of the acrosomal cylinder;
      expansion of the cylinder begins at its apical end and proceeds toward its base,
      (2) eversion of the apical half of the acrosomal vesicle and initial contraction
      of the apical cap, (3) eversion of the basal half of the acrosomal vesicle,
      continued contraction of the apical cap, and ejection of the subacrosomal
      material and nucleus, and (4) final contraction of the apical cap and ejection of
      the acrosomal filament. During steps 2, 3, and 4, the mean forward movement of
      sperm is 12.7, 3.9, and 1.1 microns, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8305206
TI  - Identification of receptor tyrosine kinases in the rat testis.
AB  - Evidence of receptor/ligand interactions that regulate testis cell function was
      sought in order to broaden the current understanding of the molecular basis of
      testis cell function. Using reverse transcription and the polymerase chain
      reaction, we have obtained novel evidence for the expression of three mRNAs
      encoding receptor tyrosine kinases in the adult rat testis: the platelet-derived
      growth factor type A receptor (PDGF-RA), the basic fibroblast growth factor
      receptor (flg), and fetal liver kinase 1 (Flk-1). A 6.8 kb transcript encoding
      the PDGF-RA was observed in RNA prepared from testes of rats aged day 5 through
      adult, with a decline in relative abundance with increasing age after day 17.
      Analysis of mRNA from isolated cell preparations (day 21 Sertoli cells, adult
      Leydig cells, round spermatids, and primary spermatocytes) and testes depleted of
      specific cell types [ethane dimethane sulfonate (EDS)-treated and cryptorchid]
      indicated that the Leydig cell was the predominant source of this mRNA in the
      adult testis. The addition of PDGF-BB to cultures of highly purified adult rat
      Leydig cell preparations resulted in a 40% increase in LH-stimulated testosterone
      production, confirming a role for this growth factor in regulation of Leydig cell
      function. These data indicate that the Leydig cell is a principal site of action
      of PDGF in the testis.

PMID- 8305208
TI  - Confocal and fluorescence microscopic study using lectins of the distribution of
      cortical granules during the maturation and fertilization of pig oocytes.
AB  - A study was carried out to determine whether pig cortical granules (CGs) could be
      visualized using fluorescein isothiocyanate (FITC)-labelled lectins. Following
      labelling with FITC-labelled peanut agglutinin (FITC-PNA), fluorescent spots were
      observed that had a distribution during maturation and fertilization entirely
      consistent with that observed by electron microscopy. For the first 18 h of in
      vitro maturation, most of the fluorescent spots of FITC-PNA were distributed
      throughout the cortical cytoplasm. Thereafter, the CGs underwent centrifugal
      migration to form a monolayer next to the plasma membrane. Following penetration
      by sperm, fluorescent spots were extruded into the perivitelline space, where
      they aggregated forming fluorescent clumps, which subsequently formed a
      reticulate structure surrounding the egg. Fluorescence was gradually lost such
      that by 18 h after insemination none could be detected in 70% of the eggs. The
      results indicate that CGs in pig oocytes contain galactosyl-rich glycoconjugates
      and that FITC-PNA is a useful probe for their rapid visualization and
      examination.

PMID- 8305209
TI  - Effect of follicle-stimulating hormone and luteinizing hormone during bovine in
      vitro maturation on development following in vitro fertilization and nuclear
      transfer.
AB  - The effects of luteinizing hormone (LH) (0, 100, 10,000 IU/ml) and follicle
      stimulating hormone (FSH) (20 micrograms/ml) supplementation during in vitro
      maturation of slaughterhouse-derived oocytes on polar body formation and embryo
      development subsequent to in vitro fertilization and nuclear transfer were
      evaluated. Gonadotropin supplementation of maturation medium in the presence of
      serum neither enhanced the proportion of oocytes forming a polar body nor
      significantly affected development following in vitro fertilization or nuclear
      transfer, except at the highest LH concentration. A very high concentration of LH
      (10,000 IU/ml) significantly decreased polar body formation, initial cleavage,
      and blastocyst development (P < 0.05).

PMID- 8305210
TI  - Origin of a sperm motility inhibitor from boar seminal plasma.
AB  - We have investigated the origin of the sperm motility inhibitor (SPMI) from boar
      seminal plasma. SPMI was measured by its capacity to inhibit the motility of
      demembranated spermatozoa and by an enzyme-linked immunosorbent assay (ELISA).
      Among the various reproductive and now reproductive tissues and fluids tested,
      only the seminal vesicle fluid and seminal plasma contained significant amounts
      of SPMI biological activity and SPMI antigen. Like other seminal vesicle fluid
      proteins, SPMI is diluted 6- to 8-fold upon ejaculation. By immunohistochemical
      detection at the light microscope with antibodies obtained from rabbits immunized
      with SPMI purified from boar seminal plasma, SPMI was found in the cytosol and/or
      on the plasma membrane bordering the lumen of the seminal vesicles. At the
      electron microscope level, SPMI appeared to be present only on the surface of the
      secretory cells. The data indicate that SPMI originates from a single tissue, the
      seminal vesicle, and suggest that only the mature form present on the luminal
      surface of the gland can react with the antibody generated from rabbits immunized
      with the secreted form of SPMI.

PMID- 8305211
TI  - Mitogenic and cytogenetic evaluation of transforming growth factor-beta on murine
      preimplantation embryonic development in vitro.
AB  - Slow cleavage rate has been a major contributory factor influencing embryo
      morphology in in vitro fertilization (IVF) programs. The role of transforming
      growth factor-beta (TGF beta 1) in improving this characteristic was evaluated
      using the murine model. Replicate batches of eight-cell compacting embryos from
      superovulated mice were divided into three groups. Group A were treated with 0.3
      ng/ml TGF beta 1 at the initial compacting stage, followed by a second treatment
      of 0.1 ng/mL 22 h later at the cavitating stage; group B received 0.3 ng/ml TGF
      beta 1 at the cavitating stage; group C were controls. The percentages of treated
      embryos reaching fixed embryonic stages, total cell number (TCN), mitotic index,
      and incidence of chromosome anomalies were monitored. The percentage of embryos
      reaching the cavitating, expanded, hatching, and hatched stages in both treatment
      groups were not significantly different from control (96.6% +/- 4.2% to 37.7% +/-
      12.7% vs. 95.3% +/- 7.3% to 47.0% +/- 3.5%; P > 0.05). Values between the two
      treatment groups were also not significantly different. Embryos in groups A and B
      produced significantly greater TCN at expanded blastocyst and hatching stages
      compared to controls (Group A: 107.0 +/- 18.9 vs. 89.9 +/- 17.4, P < 0.05 and
      125.5 +/- 16.4 vs. 113.9 +/- 12.1, P < 0.05; Group B: 107.9 +/- 14.0 vs. 89.9 +/-
      17.4, P < 0.05 and 124.9 +/- 17.4 vs. 113.9 +/- 12.1, P < 0.05). Values, however,
      were not significantly different between treatment groups.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8305212
TI  - Cryogenic protection of oocytes with antifreeze proteins.
AB  - Proteins belonging to a family of compounds known as "antifreeze proteins"
      interact with oocytes and protect the oolemma from damage at cryogenic
      temperatures. Experiments were performed with pig oocytes rapidly cooled to
      cryogenic temperatures in vitrifying solutions with and without antifreeze
      proteins. Four different types of antifreeze polypeptides and glycoproteins were
      tested. The integrity of the oolemma was examined with Fluorescein Diacetate
      (FDA) staining and morphological examinations. Results show that the pig oocyte
      oolemma is a primary site of injury during exposure to low temperatures and that
      all the different proteins have a similar ability to interact with and protect
      the oolemma. Our results may be important in developing solutions for long-term
      preservation of oocytes at cryogenic temperatures (cryopreservation).

PMID- 8305213
TI  - cis-acting DNA elements involved in oocyte-specific expression of mouse sperm
      receptor gene mZP3 are located close to the gene's transcription start site.
AB  - We report that cis-acting DNA elements involved in oocyte-specific expression of
      the mouse sperm receptor gene (mZP3) are located close to the gene's
      transcription start site. Mice bearing a transgene that consists of only 153 nt
      of mZP3 5'-flanking region fused to the firefly luciferase gene (153-ZP3/LUC)
      expressed the reporter gene in ovary not in a wide variety of tissues; although
      two of three lines carrying 153-ZP3/LUC also expressed the transgene in forebrain
      and hypothalamus. Within the ovaries of transgenic mice, luciferase activity was
      restricted to growing oocytes. However, levels of luciferase activity in these
      oocytes were lower than those in oocytes from mice bearing transgenes that
      contain a larger segment of mZP3 5'-flanking region (470-6,500 nt) fused to the
      firefly luciferase gene. Mice bearing a transgene that consists of 470 nt of mZP3
      5'-flanking region and mZP3 intragenic sequences (ZDT) were also analyzed. The
      presence of mZP3 intragenic sequences did not result in significantly increased
      levels of firefly luciferase activity in oocytes of mice carrying the ZDT
      transgene. Overall, these results suggest that as little as 153 nt of mZP3 5'
      flanking region is sufficient to target expression of the firefly luciferase gene
      to mouse oocytes and that the mZP3 intragenic sequences probably do not contain
      enhancer elements. Rather, enhancer elements are probably present between-153 and
      -470 nt of the mZP3 5'-flanking region.

PMID- 8305214
TI  - Protein phosphorylation patterns during in vitro maturation of the goat oocyte.
AB  - Protein phosphorylation patterns were studied by radiolabelling goat cumulus
      oocyte complexes with [32P]orthophosphate for various periods of time. The
      radiolabelled denuded oocytes were assessed for nuclear status and were used
      individually for gel electrophoresis. This study demonstrated that specific
      changes in protein phosphorylations were programmed during goat oocyte
      maturation. One of the most prominent changes was a general increase in the
      phosphorylation rate at germinal vesicle breakdown (GVBD). From 8 hr of culture,
      dominant phosphoprotein bands with apparent molecular weights of 27, 31, 40, and
      50 kD were observed; they remained at this level until the metaphase II stage. In
      the molecular weight range of 65-80 kD, the protein phosphorylation pattern
      exhibited characteristic differences, with a complex series of phosphoproteins
      appearing and disappearing, duration maturation. Addition of 6
      dimethylaminopurine (6-DMAP) at the onset of culture blocked the maturation
      process after GVBD and induced a dramatic condensation of chromatin. When added
      at different times after GVBD, 6-DMAP invariably induced chromosome condensation.
      This inhibition was partly reversible; i.e., after removal of the drug, oocytes
      were able to progress only until metaphase I.

PMID- 8305216
TI  - Recent achievements in the development of radiolabeled monoclonal antibodies for
      diagnosis, therapy and biologic characterization of human tumors.
AB  - Human tumors express antigenic sites that can serve as targets for radiolabeled
      monoclonal antibodies for diagnosis, therapy and biologic characterization of
      human tumors in vivo. Over the last decade, nearly 200 clinical trials have been
      performed which demonstrate that tumors can be detected with excellent
      sensitivity and specificity. Tumors which are otherwise occult, particularly for
      colorectal (anti-CEA and anti-TAG-72 antibodies) and ovarian cancer (anti-TAG-72
      and anti-HMFG), are detected in a significant fraction of problem patients.
      Therapy using radiolabeled antibodies has been effective in lymphomas, leukemias
      and neuroblastomas, and is beginning to show promise in other solid tumors.
      Biologic characterization of tumors is likely to become more and more important
      in the future as monoclonal antibodies against oncogene products, such as her-2
      neu, are developed. Development of new antibody forms through genetic engineering
      techniques, and the continual evolution toward higher resolution imaging
      instruments, such as PET and SPECT, will lead to further clinical improvements in
      cancer detection.

PMID- 8305215
TI  - Evidence for a cannabinoid receptor in sea urchin sperm and its role in blockade
      of the acrosome reaction.
AB  - Delta-9-tetrahydrocannabinol ((-)delta 9 THC), the primary psychoactive
      cannabinoid in marihuana, reduces the fertilizing capacity of sea urchin sperm by
      blocking the acrosome reaction that normally is stimulated by a specific ligand
      in the egg's jelly coat. The bicyclic synthetic cannabinoid [3H]CP-55,940 has
      been used as a ligand to demonstrate the presence of a cannabinoid receptor in
      mammalian brain. We now report that [3H]CP-55,940 binds to live sea urchin
      (Strongylocentrotus purpuratus) sperm in a concentration, sperm density, and time
      dependent manner. Specific binding of [3H]CP-55,940 to sperm, defined as total
      binding displaced by (-)delta 9THC, was saturable: KD 5.16 +/- 1.02 nM; Hill
      coefficient 0.98 +/- 0.004. This suggests a single class of receptor sites and
      the absence of significant cooperative interactions. Sea urchin sperm contain 712
      +/- 122 cannabinoid receptors per cell. Binding of [3H]CP-55,940 to sperm was
      reduced in a dose-dependent manner by increasing concentrations of CP-55,940, (
      )delta 9THC, and (+)delta 9THC. The rank order of potency to inhibit binding of
      [3H]CP-55,940 to sperm and to block the egg jelly stimulated acrosome reaction
      was: CP-55,940 > (-)delta 9THC > (+)delta 9THC. These findings show that sea
      urchin sperm contain a stereospecific cannabinoid receptor that may play a role
      in inhibition of the acrosome reaction. The radioligand binding data obtained
      with live sea urchin sperm are remarkably similar to those previously published
      by other investigators using [3H]CP-55,940 on mammalian brain and nonneural
      tissues. The cannabinoid binding properties of this receptor appear to have been
      highly conserved during evolution. We postulate that the cannabinoid receptor may
      modulate cellular responses to stimulation.

PMID- 8305217
TI  - Radioimmunodetection and radioimmunotherapy of malignant melanoma. A review.
AB  - Radioimmunodetection utilizing monoclonal antibodies to various melanoma
      associated surface antigens has been studied by several investigators during the
      past ten years. In the early trials, antibodies were labeled with 131I or 111In,
      but now 99mTc is almost exclusively used because of its more favorable energy for
      gamma camera imaging. Excellent specificity has been achieved in most studies,
      whereas sensitivity has been less good. In a recent European multicenter study on
      493 patients sensitivity was 79% and specificity 96%. In this largest study on
      melanoma so far performed many previously unknown metastatic deposits were
      identified indicating that radioimmunodetection has a role in the management of
      metastatic disease. The clinical utility of immunoscintigraphy in localization of
      regional lymph node metastases has been documented in several investigations in
      recent years, indicating that this method can be used in the preoperative
      evaluation of patients. Radioimmunodetection has also been successfully used in
      the differential diagnosis of ocular lesions. However, conclusive evidence of
      improved patient outcome resulting from the earlier detection of melanoma lesions
      by immunoscintigraphy is still lacking. Anti-melanoma antibodies labeled with
      alpha- and beta-emitting isotopes are potential therapeutic agents, but so far
      there is little clinical experience with radioimmunotherapy of metastatic
      melanoma.

PMID- 8305218
TI  - Radioimmunodetection of prostate cancer by 111In-labeled monoclonal antibody
      against prostatic acid phosphatase.
AB  - Purified human prostate acid phosphatase (PAP) was used to generate a specific
      monoclonal antibody (FC 3001) for detection of PAP expressed by some prostatic
      carcinomas. DTPA derivatives of MoAb-F(ab')2-fragments were labeled with indium
      111 chloride. This labeled antibody was tested in 15 prostate cancer patients who
      underwent staging pelvic lymphadenectomy; 9 of them received labeled antibody
      alone whereas 6 received simultaneous injections of labeled and unlabeled
      antibody with two dose levels (40 or 80 mg). Biodistribution data obtained by
      direct blood measurements and imaging procedures indicated that simultaneous
      injection of unlabeled antibody reduced both the blood elimination rate and the
      accumulation in the liver. Accumulation of the radionuclide in pelvic lymph node
      metastases was observed in some patients but in a couple of patients accumulation
      was noted also in normal lymph nodes. The method cannot in its present design
      replace staging pelvic lymphadenectomy and further studies are needed for
      elaboration of clinically useful radioimmunodetection methods.

PMID- 8305219
TI  - Radioimmunodetection of ovarian cancer.
AB  - Radioimmunoscintigraphy (RIS) is a potentially valuable method for the detection
      of primary, secondary and recurrent malignant tumours. Antigens that have been
      used for monitoring as well as for RIS of ovarian carcinomas include CA 125,
      PLAP, HMFG, and CA 19-9. Between 70 and 100% of the tumours have been detected at
      RIS when these antigens have been used. Conventional methods, e.g., computerized
      tomography (CT) and ultrasonography (US), demonstrate similar or lower detection
      rate than RIS for tumour diagnosis. RIS gives additional information to
      conventional radiological methods (CT and US) for the detection of occult ovarian
      carcinomas. A review of earlier investigations is given and our own recent
      results using PLAP as a target antigen are presented. The future potential of the
      technology is discussed.

PMID- 8305220
TI  - Radioimmunodetection of head and neck cancer. A review.
AB  - Radiolabeled antibodies can add a dimension in the diagnostic imaging and staging
      of metastatic head and neck malignancies. In the oral cavity, oropharynx and
      larynx the vast majority of malignancies are squamous cell carcinomas. This
      common cellular origin makes it feasible to search these neoplasms for
      appropriate tumor-associated antigens which can be used for
      radioimmunoscintigraphy. The pretherapeutic staging of head and neck
      malignancies, including salivary gland tumors, is based on clinical findings and
      conventional radiology (computerized tomography, magnetic resonance imaging,
      ultrasonography). The routine use of monoclonal antibodies for imaging head and
      neck malignancies was made possible by the production of several monoclonal
      antibodies to tumor-associated membrane antigens. A review of the clinical trials
      reported in the literature, and our own results with 111In-labeled anti
      carcinoembryonic antigen (CEA) antibody in 42 patients are presented.

PMID- 8305221
TI  - Targeted immunotherapy. An update with special emphasis on ovarian cancer.
AB  - An overview of antibody-guided immunotherapy for neoplasia is presented. The
      diversity of the antibody molecule is highlighted, through the many sophisticated
      strategies proposed and employed, to overcome a number of problems impeding
      successful targeting. An update of radioimmunotherapy of ovarian cancer is
      presented and the exciting concepts that are introduced to the field of targeted
      cancer therapy by molecular biology and genetic engineering are addressed.

PMID- 8305222
TI  - A novel technetium-99m labeled monoclonal antibody (174H.64) for staging head and
      neck cancer by immuno-SPECT.
AB  - A novel murine monoclonal antibody (MAb 174H.64) was labeled with 99mTc by a
      direct method. MAb 174H.64 detects a cytokeratin-associated antigen which is
      expressed by over 90% of all squamous cell carcinomas. Panendoscopy, sonography
      and computerized tomography scan were performed in all cases as well as magnetic
      resonance imaging (in selected patients). Pre-operative immunoscintigraphy was
      performed in 21 patients with histologically proven primary carcinomas (18 with
      remaining primary tumors and 3 with lymph node recurrences). Scintigraphic images
      were obtained 4-6 h after injection of 1.1 GBq of the 99mTc-labeled antibody (2
      mg). Late images were acquired 18 to 24 h after injection. Single-Photon-Emission
      Computed Tomography (SPECT) of the head and thorax was performed in all patients.
      The primary tumors were immunoscintigraphically visualized in all 18 patients
      with remaining primary tumor. Fifteen of 18 loco-regional lymph node metastases
      were visualized by immunoscintigraphy (the smallest lesions had a diameter of < 1
      cm), in one patient lymph node metastases were detected by immunoscan only. Two
      metastatically involved lymph nodes were identified by histology only
      (micrometastases). Distant metastases were present in 3 patients, of which two
      were identified by immunoscintigraphy. Immuno-SPECT according to this method was
      a sensitive and specific imaging modality for preoperative staging of patients
      with squamous cell carcinoma of the head and neck and detected lymph node
      metastases with higher accuracy than conventional clinical and imaging
      modalities.

PMID- 8305223
TI  - Bone marrow immunoscintigraphy compared with conventional bone scintigraphy for
      the detection of bone metastases.
AB  - Immunoscintigraphy of haematopoetic bone marrow was compared to conventional bone
      scanning in 141 patients with malignant disease. Forty patients had breast
      cancer, 25 prostatic carcinoma, 14 kidney or bladder cancer, 13 bronchial
      carcinoma, 39 malignant lymphoma and 10 multiple myeloma. A total of 18,800
      skeletal regions were evaluated. Marrow scans showed more metastatic lesions than
      bone scanning in all patient subgroups. Computerized tomography was concordant
      with bone marrow scintigraphy in 83.3% of 323 skeletal sites. Bone marrow scans
      in 30 control patients with fever of unknown origin were abnormal only in 3
      patients and in only 7 out of 2,135 skeletal regions examined. In patients with
      malignant lymphoma, bone marrow histology or aspiration cytology was concordantly
      positive in 14 and concordantly negative in 17 patients. We conclude that
      immunoscintigraphy of haematopoetic bone marrow provides a reliable, sensitive
      and safe novel approach for non-invasive detection of metastatic spread to the
      skeleton.

PMID- 8305224
TI  - Image subtraction analysis with technetium-99M labeled monoclonal antibody and
      colloid for evaluation of liver lesions. Phantom measurements and patient
      studies.
AB  - The ideal radiolabeled monoclonal antibodies (MoAbs) against cancer antigens are
      taken up by liver metastases; the background activity of normal liver, however,
      causes problems for delineation and detectability. In order to study these
      phenomena, a liver phantom containing hot and cold lesions of different sizes
      (diameters 5-32 mm) was constructed. It was placed into an elliptic cylindrical
      container representing a cross section of the abdomen. The specific activities in
      hot lesions varied from 1.85 to 14.8 MBq/ml, whereas liver phantom and cylinder
      activities were kept constant during different measurements. Lesions of size 1.3
      cm3 could be detected without any subtractions, if the signal to background ratio
      was larger than 1.2. Lesions larger than 5 mm in diameter could also be detected
      using subtraction, which gave additional information by a factor 2-9, when the
      lesion sizes varied from 0.3 to 5.3 cm3 and when the specific activity in the
      lesions was at least twice as high as in adjacent liver. This subtraction
      technique was applied in 32 breast and lung cancer patients after injecting about
      1,000 MBq 99mTc-labeled anti-CEA MoAb; 24 h after the antibody injection 75 MBq
      99mTc-phytate was injected. The phytate + residual MoAb image was subtracted from
      the original antibody image. Thirteen patients had liver metastases verified by
      (CT, US), but only four patients had clearly observable abnormal liver uptakes in
      planar MoAb images. In 9 cases, additional information concerning liver
      metastases was obtained by subtraction technique. To judge by our phantom
      measurements the enhanced detectability was not an artefact.

PMID- 8305225
TI  - Radioimmunoimaging of non-small cell lung cancer with 111In- and 99mTc-labeled
      monoclonal anti-CEA-antibodies.
AB  - Radiolabeled monoclonal anti-CEA antibodies were used for radioimmunolocalization
      (RIL) of non-small cell lung cancer; in 30 patients with 111In labeled anti CEA
      F(ab')2 fragment (BW 431/31) and in 16 with 99mTc-labeled intact MoAb (BW
      431/26). RIL results were compared with those of other imaging modalities.
      Paraffin sections from some patients were also studied immunohistochemically
      using anti-CEA antibody. Patients with 111In labeled MoAB were imaged twice 1-4
      days after injection and for image enhancement pulmonary and liver/spleen
      subtraction were performed. Twenty-seven of 28 primary tumors were positive and
      metastases were detected in all patients. The total number of lesions was 78 of
      which 61 (78%) could be detected by RIL. For verification CT was applied to the
      study of 46 lesions detected by RIL. We found 6 unknown lesions subsequently
      verified histologically. Using subtraction techniques we detected 9 lesions in 4
      patients, later verified as pulmonary metastases, not detected in unprocessed
      images. Pleural, mediastinal and pericardial lesions were also better delineated
      in subtracted images than in unprocessed images. Imaging of non-small cell lung
      cancer with 99mTc-labeled MoAB was performed twice 4-24 h after injection. RIL
      results were compared with other imaging methods; CT US, conventional
      radiography, and immunohistochemistry. Twelve out of 16 patients with suspected
      or known lung cancer had positive immunoscintigrams; 19 of 25 lesions could be
      detected by RIL. There were 5 false positive and 2 true negative findings.
      Immunoperoxidase (IP) stainings of paraffin sections of the tumours from 7
      patients were performed using two different anti-CEA antibodies; BW 431/26 and
      ZCEA1. None of the seven tumors examined by immunohistochemistry were negative
      when stained by BW 431/26, which was the antibody used for immunoscintigraphy.

PMID- 8305226
TI  - Evaluation of plasma levels of thymidine kinase and mutated p53 in 81 patients
      with newly diagnosed malignant lymphoma.
AB  - We analysed diagnostic phase plasma levels of thymidine kinase (TK) and mutated
      p53 in 81 patients with malignant lymphoma. Forty-three (53%) patients had
      increased (> 10 U/l) TK activity whereas 30 (37%) were positive for the mutated
      p53 gene product. In general, patients with p53 mutation positive tumors tended
      to have higher TK activity than those without. Furthermore, patients with high
      grade non-Hodgkin's lymphoma (NHL) showed almost a linear correlation (rs = 0.79)
      between plasma levels of mutated p53 and TK. We conclude that the monoclonal
      antibody assisted detection of mutated p53 gene product may prove a useful
      adjunct to the diagnostic procedures of malignant lymphomas.

PMID- 8305227
TI  - Somatostatin receptor scintigraphy of carcinoid tumours using the [111In-DTPA-D
      Phe1]-octreotide.
AB  - Somatostatin-receptor scintigraphy using the 111In-labelled somatostatin-analogue
      octreotide ([111In-DTPA-D-Phe1]-octreotide) was performed in 40 patients with
      carcinoid tumours. In 31/40 patients, this scintigraphy proved positive compared
      with the 33/40 patients whose tumours were disclosed on CT scans. In addition, 18
      previously unidentified lesions were detected with this scintigraphy. Two of
      these lesions represented previously undetectable primary tumours. It is
      concluded that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]
      octreotide has a future role in the staging of patients with carcinoid disease.

PMID- 8305228
TI  - Electron microscopy and computed microtomography studies of in vivo implanted
      mini-TL dosimeters.
AB  - The need for direct methods of measuring the absorbed dose in vivo increases for
      systemic radiation therapy, and in more sophisticated methodologies developed for
      radioimmunotherapy. One method suggested is the use of mini-thermoluminescent
      dosimeters (TLD). Recent reports indicate a marked loss of signal when the
      dosimeters are used in vivo. We investigated the exterior surface of the
      dosimeters with scanning electron microscopy and the interior dosimeter volume
      with computed microtomography. The results show that the dosimeters initially
      have crystals uniformly embedded in the teflon matrix, with some of them directly
      exposed to the environment. After incubation in gel, holes appear in the
      dosimeter matrix where the crystals should have been. The computed
      microtomographic images show that crystals remain in the interior of the matrix,
      producing the remaining signal. We conclude that these dosimeters should be very
      carefully handled, and for practical use of mini-TLDs in vivo the dosimeters
      should be calibrated in equivalent milieus. An alternative solution to the
      problem of decreased TL efficiency, would be to coat the dosimeters with a thin
      layer, of Teflon, or other suitable material.

PMID- 8305229
TI  - Radioimmunotherapy with 90Y-labeled monoclonal antibodies in a nude mouse ovarian
      cancer model.
AB  - Tumor stroma contains much fibrin, and so monoclonal antifibrin antibody can
      accumulate in tumors. We treated nude mice bearing human ovarian carcinoma
      xenografts with 90Y-labeled monoclonal antifibrin antibody Fab fragments
      administered intratumorally. The survival time vs. a control group was
      significantly prolonged and tumor growth rate was decreased. Another group of
      animals was treated with 90Y-labeled OC 125-monoclonal antibody; these mice
      received the antibodies intratumorally, intraperitoneally or intravenously. The
      survival time was longest in the intratumorally treated group. There was no
      significant difference in survival between 90Y-labeled OC 125 and antifibrin in
      the intratumorally treated animal groups. The tissue activity distribution
      studies revealed that bone marrow is the critical organ. Intratumorally injected
      monoclonal 90Y-antifibrin antibodies were retained at least 36 h (up to 50% of
      injected activity per gram tumor tissue) in the xenograft after one treatment,
      causing cell death. Beta-camera imaging and immunohistochemistry were performed
      for studies of the correlation between 90Y activity and fibrin distribution in
      tumor specimens. These results were in concordance. In conclusion, intratumoral
      administration seems suitable for radioimmunotherapy, with an antibody that
      targets stromal structures. The accumulation can be successfully monitored by a
      beta-camera.

PMID- 8305230
TI  - Radioimmunotherapy dosimetry--a review.
AB  - Results from therapeutic trials in systemic radiation therapy with radiolabelled
      monoclonal antibodies are difficult to compare, because of lack of accurate
      dosimetry. This applies macroscopically as well as microscopically for both
      tumours and normal tissues. For treatment planning in radioimmunotherapy both the
      macroscopic and the microscopic absorbed dose distribution must be known. The
      former is based on a proper knowledge of parameters, such as activity
      quantitation techniques in both planar and SPECT imaging, different correction
      techniques, and high activity measurements. Absorbed dose calculations and
      treatment planning techniques are based on analytical or Monte Carlo
      calculations. The PET technique with higher resolution is also suggested for
      radioimmunotherapy planning. Accurate in vivo absorbed dose measurement
      techniques to verify the calculated absorbed doses are needed in treatment
      planning. Monitoring the absorbed rate is desirable to assess radiobiological
      effect. Several ways of enhancing the therapeutic ratio are suggested, especially
      novel technique with extracorporeal immunoadsorption. An important topic is small
      scale dosimetry, which is based on techniques for detailed imaging of activity
      distributions to calculate the absorbed dose distribution.

PMID- 8305231
TI  - Animal models for radiolabeled monoclonal antibodies in cancer research.
AB  - A review of the different animal tumor model systems used for radiolabeled
      monoclonal antibody research is given. Problems within the field of
      radioimmunotargeting are presented, and the tumor models are discussed in
      relation to the types of problems which can be investigated, and the ability of
      the models to answer different questions.

PMID- 8305232
TI  - Positron emission tomography of monoclonal antibodies.
AB  - A review on the use of monoclonal antibodies labeled with positron emitting
      nuclides is presented. Potential radionuclides for labeling are e.g. 18F, 55Co,
      64Cu, 66Ga, 68Ga, 76Br, 89Zr and 124I. Radionuclides with short half-lives may be
      utilized especially by pretargeting approaches. Gallium-isotopes have also been
      coupled to antibodies, using chelation methods. One promising nuclide for
      antibody labeling seems to be 124I (t1/2 = 4.2 d) as radioiodination of
      antibodies is a well-characterized procedure. Some of our own studies using 124I
      labeled monoclonal antibodies in a nude mouse and rat human ovarian cancer
      xenograft are reported.

PMID- 8305233
TI  - Search for new and improved radiolabeling methods for monoclonal antibodies. A
      review of different methods.
AB  - The radiolabeling of monoclonal antibodies for routine clinical applications have
      been intensively researched during the past decade. The traditional radiolabeling
      methods are direct radioiodination using oxidative reagents, such as chloramine
      T, and coupling metals by use of bifunctional chelates like diethylenetriamine
      pentaacetic acid (DTPA). More recently technetium labeling has also been used. In
      this review the selection of different radioisotopes is discussed as well as the
      various traditional or newer methods to introduce the radiolabel into the
      antibody structure. Labeling methods for radiohalogens, for technetium and
      rhenium isotopes, and for 3-valent cation radiometals are reviewed. Some of the
      newer methods offer simplified labeling procedures, but usually the new methods
      are more complicated than the earlier ones. However, new labeling methods are
      available for almost any radioelement group and they may result in better
      preserved original nature of the antibody and lead to better clinical results.

PMID- 8305234
TI  - Alternative technologies to generate monoclonal antibodies.
AB  - Several new technologies to generate and modify established hybridomas that
      produce monoclonal antibodies have recently been presented and further
      development should make them more suitable for diagnostic and therapeutic
      techniques. Different proteolytic procedures have been used for the fragmentation
      of intact antibodies to Fab2' and Fab fragments and recombinant DNA techniques
      have made it possible to obtain chimeric, humanized, Fv fragments and single
      chain Fvs. A review of the new approaches is presented and the future
      implications are discussed.

PMID- 8305235
TI  - Monoclonal antibodies for diagnosis and potential therapy of small cell lung
      cancer--the ganglioside antigen fucosyl-GM1.
AB  - Lung carcinomas represent a highly heterogenous group of tumors, which includes
      small cell lung cancer (SCLC). The ganglioside fucosyl-GM1 (FucGM1) was
      originally identified as a highly selective marker for SCLC. A number of
      monoclonal antibodies against FucGM1 have been produced against the purified
      ganglioside, and their specificity validated. With monoclonal antibodies, FucGM1
      has been detected in tissues as well as in serum samples from SCLC patients. A
      sensitive, quantitative assay method for FucGM1 was developed based on
      scintillation proximity immunoassay (SPA): A specific monoclonal antibody against
      FucGM1 is bound to immunosorbent particles that contain a fluor. When
      radiolabelled FucGM1 binds to these particles, the fluor is excited, and the
      photons emitted can be measured directly in a beta-counter. This sensitive assay
      for FucGM1 has several potential diagnostic applications: differential diagnosis
      of SCLC, development of serum assays for diagnosis and monitoring of disease
      progression, and monitoring of patient response to therapy. The expression of
      FucGM1 in SCLC cells is heterogeneous, and may depend on the differentiated state
      of tumor cells. However, monoclonal antibodies specific for FucGM1 may have
      important future applications for radioimmunoimaging as well as in immunotherapy
      for SCLC.

PMID- 8305236
TI  - Improving radioimmonotargeting of tumors. Variation in the amount of L6 MAb
      administered, combined with an immunoadsorption system (ECIA).
AB  - Extracorporeal immunoadsorption (ECIA) is a new method for the selective removal
      of circulating radiolabeled monoclonal antibodies (MAb) from plasma to increase
      the uptake in tumor versus normal tissues (T/N-ratio). To ascertain whether the
      amount of MAb affects T/N ratios immediately and 24 h after ECIA, we used a rat
      model with two tumor sites--one intramuscular (im) and one below the subrenal
      capsule (SR). Extracorporeal immunoadsorption was done with an avidin-agarose
      column after injection of 125I-labeled biotinylated L6 MAb. The animals received
      10, 50 or 250 micrograms of L6 only (controls), or followed by ECIA. The efficacy
      of the procedure in removing plasma activity was 80-95%. For both tumor sites,
      the highest T/N-ratios were obtained with 10 micrograms L6. All T/N-ratios
      significantly improved for SR tumors by a factor ranging from 3.2 (lung) to 12.6
      (bone marrow). The T/N-ratios were still elevated 24 h after ECIA. Injection of
      larger amounts of MAb, probably causing a higher degree of tumor saturation, will
      not necessarily improve the T/N ratio after ECIA.

PMID- 8305237
TI  - High resolution pinhole SPECT for tumor imaging.
AB  - High-resolution, non-invasive, 3D-imaging techniques would greatly benefit the
      investigation of the localization properties of tumor-specific
      radiopharmaceuticals in laboratory animals. The present study reports how pinhole
      SPECT can be applied to tumor localization studies in small laboratory animals to
      provide high resolution SPECT images in vivo. Pinhole SPECT was performed using a
      rotating scintillation camera, equipped with a pinhole collimator. The
      sensitivity of a 2 mm diameter collimator at 45 mm from the source is 90 cps/MBq
      for 99mTc. The planar spatial resolution at a 45 mm distance is 2.2 mm. The
      transaxial spatial resolution, with a distance of 45 mm between the collimator
      aperture and the axis of rotation, is 3.1 mm. For SPECT imaging, spatial
      linearity is preserved across the usable field-of-view. The major advantage of
      the high resolution properties of pinhole tomography is demonstrated by the
      enhanced lesion-to-normal-brain uptake ratio achieved on tomographic slices as
      compared to planar images. For example, 201Tl tumor-to-normal-brain uptake ratios
      of 1.1 to 1.3 observed on planar images, corresponded to ratios ranging from 3.2
      to 3.7 on the SPECT slices. Examples of the activity distributions of two
      radiopharmaceuticals in tumor and in normal brain for sagittal and coronal images
      are given. In all cases, tumors are clearly delineated on the pinhole SPECT
      slices. The present study shows that pinhole SPECT performed with standard SPECT
      instrumentation can give high spatial resolution images, with a FWHM
      approximately 3 mm and a sensitivity approximately 100 cps/MBq for 99mTc.

PMID- 8305238
TI  - Beta camera low activity tumor imaging.
AB  - A new technique, the beta camera, to complement film autoradiography, with fast
      quantitative imaging of beta particle-emitting radionuclides has been developed.
      It consists of a thin plastic scintillator and a light-sensitive microchannel
      plate detector. The thin tissue sample is mounted on the scintillator. Our first
      system had a high background and a moderate spatial resolution of 900 microns. We
      now report an improved system with a photomultiplier tube mounted on the
      scintillator of the microchannel plate detector. Only events registered by both
      detectors are accepted. A fast coincidence unit processes the signals, and if a
      time overlap exists, an event is generated in the beta camera. In the coincidence
      mode, images with low activity distribution of 201Tl (count rate 1 s-1) in 50
      microns-thick slices of a human glioma tumor could be recorded with a spatial
      resolution of 500 microns.

PMID- 8305239
TI  - Immunoconjugate stability in vivo measured by label release from 125I or 99mTc
      antibody coated cells kept in intraperitoneal diffusion chambers in mice.
AB  - The present work demonstrates how intraperitoneal (i.p.) diffusion chambers (DC)
      can be used to investigate the in vivo stability of the bond between an antibody
      and its radioactive label. A monoclonal antibody (MoAb) was labelled with 125I or
      99mTc. The 125I-labelled preparation showed high stability in vitro, since little
      radioactivity eluted from incubated DC containing 125I-MoAb bound to specific,
      fixed target cells. Similarly, when we evaluated the 125I-MoAb in vivo by using
      the i.p. DC the stability was intact. The 99mTc-MoAb was also stable in vitro,
      with only about 10% of the radioactivity lost after 48 h. However, when tested in
      vivo, about 50% of the 99mTc label was lost after 1 day, increasing to 60% after
      2 days. Hence, by carrying out preclinical in vivo stability testing with i.p. DC
      method we discovered that an immunoconjugate with high stability as tested in
      vitro, in fact was unstable in vivo and probably unsuited for clinical use.

PMID- 8305240
TI  - Radioimmunolocalization of hepatic metastases and subcutaneous xenografts from a
      human colonic cancer in the nude rat. Aspects of tumour implantation site and
      mode of antibody administration.
AB  - Antibody localization was analyzed following intraperitoneal (i.p.) or
      intravenous (i.v.) injection of the 125I-labelled anti-CEA-MAb I-38S1 in 44 nude
      rats, in order to evaluate the influence of tumour implantation site and the
      route of MAb administration. The animals were xenografted with a human colonic
      cancer (LS 174 T), either in the form of hepatic metastases, subcutaneous (s.c.)
      tumours or both. Tissue measurements, 4 days after MAb injection, showed better
      uptake for hepatic than for s.c. tumours, irrespective of the route of antibody
      administration. Antibody accumulation per g liver metastases was not size
      dependent for noduli weighing between 4 and 1,110 mg. MAb excretion evaluated in
      20 animals and blood activity studied in 11 rats were equivalent 24-96 h
      following i.p. and i.v. injection. Dissimilar autoradiographic patterns were seen
      in hepatic metastases with predominantly peripherally located clusters following
      i.p. and more homogeneously distributed grains after i.v. MAb administration. The
      results indicate that tumour implantation site has a quantitative, and the route
      of administration at least a qualitative impact on the tumour accretion of anti
      CEA MAb I-38S1 in the present xenograft model.

PMID- 8305242
TI  - [Assessment of arterial occlusive disease with Duplex sonography. Prospective
      study].
AB  - Occlusive disease involving the renal arteries represent a major cause of curable
      hypertension and improvement of renal dysfunction. Angiography is still the major
      diagnostic procedure. Isotopic methods with Captopril and split-function studies
      have shown high incidence of false-positive and false-negative results. Colour
      flow Duplex-Scan renders possible the visualization of the aorta and renal
      arteries, is noninvasive and combines morphologic and hemodynamic evaluation. To
      assess its efficacy in the diagnosis of renal artery occlusive disease, a
      prospective blind study was undertaken in 24 patients, 48 renal arteries, 15
      women and 9 men, with mean age of 44 years. Scans of the aorta and renal arteries
      at the origin, along its extension and at the renal hilum were obtained using and
      ATL Ultrmark 9 with 3.0 MHZ probe Velocity measurements were obtained at the
      aorta and along the renal arteries. Criteria for a positive examination were:
      focal acceleration with a reduction of the flow velocity at the hilum. Absence of
      flow in a properly visualized renal artery was considered as occlusion. All
      patients had digital subtraction arteriography. In 1 patient the non-invasive
      examination was inadequate. In the remain 23 patients the exam was considered
      adequate. False-positives were 4.8%; false-negatives 8.7%. Sensitivity,
      specificity and accuracy were respectively 91.7%, and 95.7% and 93.5%. These
      results suggest that non-invasive assessment of renal artery occlusive disease is
      feasible and accurate when compared to angiography, thus providing a useful tool
      for screening hypertensive patients.

PMID- 8305241
TI  - Characterization and uptake of radiolabelled meta-iodobenzylguanidine (MIBG) in a
      human neuroblastoma heterotransplant model in athymic rats.
AB  - Cells from an established human neuroblastoma cell line, SH-SY5Y, were
      demonstrated to grow and form solid tumours in nude rats. This cell line, which
      is an adrenergic subclone of the SK-N-SH cell line, has previously been used in
      differentiation model studies. The tumours retained the neuronal phenotype of the
      cultured cells, as evidenced by the expression of neuron-specific enolase (NSE)
      and chromogranin A + B. The transcription factor Isl-1, a protein expressed in
      subsets of neurons and endocrine cells as well as in neuroblastoma cells, was
      also expressed in the transplanted tumours, thus further verifying the retained
      phenotype of the cells under in vivo conditions. At scintigraphy utilizing 123I
      MIBG the optimal tumour/background ratio was obtained 20 h after injection. The
      assessment of tissue/serum ratios showed the highest uptake in the spleen (0.067%
      per gram of inj. activity), neuroblastoma tumours (0.067% per gram of inj.
      activity) and in the adrenals (0.065% per gram of inj. activity).

PMID- 8305243
TI  - Leukocyte count as a predictor of the severity ischaemic heart disease as
      evaluated by coronary angiography.
AB  - Increased white blood cell count has been reported associated with increase risk
      of coronary heart disease. We studied the relationship of white blood cell count
      to the 5 year incidence of coronary heart disease mortality in 152 men, without
      myocardial infarction or infection in the 6 months prior to the study. The
      coronary heart disease was determined by coronary arteriography study in all
      patients. None was treated by revascularization procedures (surgical or
      percutaneous transluminal coronary angioplasty). The severity of coronary heart
      disease was assessed by Gensini's Score and number of main coronary arteries with
      significant stenosis. The white blood cell count showed a positive correlation
      with Gensini's Score (r = 0.45, p < 0.01), and was significantly higher in the
      patients with three vessels disease (one vessel = 7084 +/- 1679 leukocytes/mm3;
      two vessels = 7768 +/- 1860 leukocytes/mm3; three vessels = 8174 +/- 2016
      leukocytes/mm3; p < 0.05). The patients who died differed significantly from the
      survivors as regards total leukocyte count (8309 +/- 2271 against 7548 +/- 1702
      cells/mm3; p < 0.05). Multivariate analysis, using a stepwise logistic
      regression, identified the white blood cell count as the more strong independent
      predictive variable for Gensini's Score (r = 0.42, p < 0.001). We conclude that,
      in our experience, increased white blood cell count may contribute to the
      initiation and progression of the coronary heart disease, and was associated with
      a shorter subsequent survival time.

PMID- 8305244
TI  - ["Severe" congestive heart failure at a medical center].
AB  - Heart failure (HF) is a dynamic clinical syndrome depending on multiple
      hemodynamic and neurohormonal factors. This syndrome concerns not only left
      ventricular systolic dysfunction but also left ventricular diastolic dysfunction
      and right ventricular dysfunction. Clinical features and therapeutic approaches
      are different for each of them. NYHA class IV is just one of the various
      prognostic factors of heart failure; consequently, severe heart failure is not
      synonymous of NYHA class IV. OBJECTIVE: To study hospitalised patients with heart
      failure in NYHA class IV, in order to characterise the predominant dysfunction,
      and analyze evolution and mortality. DESIGN: A retrospective analysis of a
      prospective study. SETTING: Hundred and eight hospitalised patients (1985-89).
      Patients with chronic obstructive pulmonary disease and acute myocardial
      infarction were excluded. PATIENTS: Sixty nine patients: 29 female and 40 male,
      aged 18 to 81 years old (m = 59 +/- 15.5). METHODS: Patients were clinically
      examined and had chest radiographs, electrocardiogram and M + 2D mode
      echocardiogram. Three groups were identified: Group I-patients with predominant
      left ventricular systolic dysfunction; Group II-patients with predominant left
      ventricular diastolic dysfunction; Group III-patients with predominant right
      ventricular dysfunction. RESULTS: 41% of the patients had coronary artery
      disease; 44%, valvular heart disease; 11.8% dilated cardiomyopathy; 8.7%
      hypertrophic cardiomyopathy; 8.7% hypertensive cardiomyopathy. Fifty five percent
      of the patients were in group I and the major aetiology were coronary artery
      disease and valvular heart disease; 25% of the patients were in group II and the
      major aetiology were coronary artery disease and hypertrophic cardiomyopathy; 20%
      of the patients were in group III, all had valvular heart disease. The global
      mortality during the hospitalisation period was 15.9%, mostly group III (29%) and
      II (17%). CONCLUSIONS: Heart failure patients in NYHA class IV formed an
      heterogeneous group, requiring individualised therapeutic approaches. Left
      ventricular systolic dysfunction was the major pathophysiological mechanism,
      however, diastolic dysfunction and right ventricular dysfunction were frequent.
      Coronary artery disease presented as a frequent aetiology of heart failure,
      resulting in diastolic and/or systolic dysfunction. Valvular heart disease can be
      present as left ventricular systolic or diastolic dysfunction or as a right
      ventricular dysfunction, depending on the valvulopathy and the time of evolution.
      Echocardiography, in association with clinical features, has been very useful for
      each patient approach, allowing HF aetiology and pathophysiological mechanisms
      characterisation. The low mortality observed in this study was related certainly
      to the correction of precipitating factors, together with early etiologic
      diagnosis and pathophysiological characterisation, and adequate individualised
      treatment.

PMID- 8305245
TI  - [Blood glucose and insulin in arterial hypertension. The elderly hypertensive
      patient].
AB  - The clinical importance of relationship between insulin resistance,
      hyperinsulinemia and high blood pressure is not yet fully understood. The aim of
      this study was to evaluate the influence of age in the relation between
      hyperglycemia, hyperinsulinemia and hypertension (HT). Two groups of patients
      with moderate to severe essential hypertension, aged < 65 (n = 40) and > or = 65
      (n = 55) were compared with two other groups of normotensive subjects (NT)
      matched for sex (n = 14) and age (n = 18). The radioimmunoassay method and
      glucose oxidase methods were used to evaluate plasma insulin and plasma glucose
      concentrations. The global analysis shows: The plasma glucose level was
      significantly lower (p < 0.02) in NT group (n = 32; glycemia: 67.52 +/- 44 mg/dl)
      than in the HT group (n = 95; glycemia: 86.25 +/- 34.7 mg/dl. Further more the
      plasma insulin level in NT (3.37 +/- 3.18 microU/ml) was also lower than in HT
      (4.29 +/- 3.08 microU/ml) although without statistical significance. The patients
      (HT) aged < 65 years old had higher glycemia (85.76 +/- 26.8 mg/dl) and
      insulinemia (4.92 +/- 3.56) than NT of same age (glycemia: 59.0 +/- 11.8 mg/dl,
      insulinemia: 2.86 +/- 1.86), respectively p < 0.001 and p < 0.05. In HT aged > or
      = 65 the glycemia (82.38 +/- (9.67 mg/dl) was higher than in the NT matched group
      (65.5 +/- 20.36 mg/dl), p < 0.01, but plasma insulin was not different in the two
      groups (3.88 +/- 2.63 and 3.80 +/- 2.27 microU/ml).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8305246
TI  - [Diuretics in the treatment of heart failure].
AB  - Diuretics, together with other drugs and general measures, are of prime
      importance in the medical treatment of most heart failure patients, namely those
      with acute pulmonary oedema and overt congestive heart failure. Their beneficial
      effects result not only from preload and afterload reduction, but also because
      diuretics are able to improve responses to nitrates and ACE-inhibitors. The
      appropriate utilisation of diuretics in heart failure therapy frequently involves
      the use of efficient small doses and drug associations, namely between loop
      diuretics, thiazides, potassium sparing agents and spirolactone. Physicians must
      choose the drug carefully, its dosage, time and route of administration,
      according to the patient's characteristics: heart failure clinical syndrome, age,
      activity level, systolic or diastolic, left or right ventricular dysfunction, and
      associated diseases. The role of diuretics in the treatment asymptomatic systolic
      left ventricular dysfunction and oligosymptomatic diastolic ventricular
      dysfunction is unclear and should remain under investigation; diuretics may be of
      benefit in treating those patients with associated diseases, for example arterial
      hypertension and mild chronic renal failure.

PMID- 8305247
TI  - [Primary tricuspid valve insufficiency. Report of 2 clinical cases].
AB  - Two case reports of primary tricuspid regurgitation are presented which diagnoses
      were made in mean adult life after a long period of few symptoms. The clinical
      outcome of the two cases was uneven in the sense that only one of them could be
      corrected with single surgical procedures. Despite relatively rare, this
      pathology could probably be turned more frequent with a complete and systematic
      echocardiographic approach. In connection with the reported cases, a review is
      made of the main etiologies and of some published reports.

PMID- 8305248
TI  - [Mitral subvalvular aneurysm: report of 3 cases].
AB  - Mitral annular subvalvar Aneurysms are a very uncommon pathology and almost
      restricted to Blacks Africans. The authors present three cases, describing their
      clinical presentation, evolution and complications. The complementary exams are
      also presented and their relevance in the diagnosis is discussed.

PMID- 8305249
TI  - [Mitral subvalvular aneurysm].
AB  - Mitral subvalvar aneurysms are a rare clinical entity and not commonly described
      in the literature. They are almost exclusive of the black population in the
      subsaharian Africa. The authors, in a bibliographic revision, present the
      different etiological theories, the pathology, the pathophysiology, the clinical
      presentation and discuss the relative value of the different diagnostic tools.
      The differential diagnosis is also discussed and the more recent methods of
      medical and surgical treatment presented.

PMID- 8305250
TI  - Kinetics of macromolecular interactions.

PMID- 8305251
TI  - Kinetic measurements of molecular interactions by spectrofluorometry.
AB  - The kinetics of antibody-antigen interactions are reviewed in terms of general
      trends observed in both polyclonal and monoclonal antibody populations. Anti
      fluorescein antibodies are featured in the review as model proteins to explore
      fluorescence-based kinetic measurements. Since the fluorescence of the
      fluorescein ligand is significantly quenched upon interaction with both
      polyclonal and monoclonal anti-fluorescein antibodies, the quenching parameter
      can be advantageously employed in measuring the rates of association (k1) and
      dissociation (k2). The near diffusion-limited k1 rates and the prolonged k2 rates
      are discussed in terms of antibody affinity and mechanisms involved in ligand
      binding. Specific prolongation effects of reagents, such as anti-metatype
      antibodies, on the dissociation rate are discussed in terms of antibody dynamics
      and conformational substates.

PMID- 8305252
TI  - MHC class I/peptide interactions: binding specificity and kinetics.
AB  - Recent developments in the preparation of soluble analogues of the major
      histocompatibility complex (MHC) class I molecules as well as in the application
      of real time biosensor technology have permitted the direct analysis of the
      binding of MHC class I molecules to antigenic peptides. Using synthetic peptide
      analogues with cysteine substitutions at appropriate positions, peptides can be
      immobilized on a dextran-modified gold biosensor surface with a specific spatial
      orientation. A full set of such substituted peptides (known as 'pepsicles', as
      they are peptides on a stick) representing antigenic or self peptides can be used
      in the functional mapping of the MHC class I peptide binding site. Scans of sets
      of peptide analogues reveal that some amino acid side chains of the peptide are
      critical to stable binding to the MHC molecule, while others are not. This is
      consistent with functional experiments using substituted peptides and three
      dimensional molecular models of MHC/peptide complexes. Detailed analysis of the
      kinetic dissociation rates (kd) of the MHC molecules from the specifically
      coupled solid phase peptides reveals that the stability of the complex is a
      function of the particular peptide, its coupling position, and the MHC molecule.
      Measured kd values for antigenic peptide/class I interactions at 25 degrees C are
      in the range of ca 10(-4)-10(-6)/s. Biosensor methodology for the analysis of the
      binding of MHC class I molecules to solid-phase peptides using real time surface
      plasmon resonance offers a rational approach to the general analysis of
      protein/peptide interactions.

PMID- 8305253
TI  - Chymotrypsin inhibitory conformation of dipeptides constructed by side chain-side
      chain hydrophobic interactions.
AB  - A complete series of configurational isomers (L-L, L-D, D-L and D-D) of a
      dipeptide Leu-Phe benzyl ester have been synthesized and assayed for
      chymotrypsin. In the conformational analysis by 400 MHz 1H NMR, the L-D and D-L
      isomers, but not the L-L and D-D isomers, showed fairly large upfield shifts (0.2
      0.4 ppm) of Leu-beta CH2 and gamma CH proton signals, indicating the presence of
      shielding effects from the benzene ring. In addition to distinct signal splitting
      of Phe-beta CH2, the NOE enhancement observed between Leu-delta CH3 and Phe
      phenyl groups revealed that these groups are in close proximity. These data
      indicated that L-D and D-L isomers form a hydrophobic core between side chains of
      adjacent Leu and Phe residues. When the dipeptides were examined for inhibition
      of chymotrypsin using Ac-Tyr-OEt as a substrate, the L-L isomer showed no
      inhibition, itself becoming a substrate. However, the other three isomers
      inhibited chymotrypsin in a competitive manner, and the D-L isomer was strongest
      with Ki of 2.2 x 10(-5) M. It was found that the D-L isomer was only slowly
      hydrolysed but the L(or D)-D isomer was not. H-D-Phe-L-Leu-OBzl with the inverse
      sequence of H-D-Leu-L-Phe-OBzl inhibited chymotrypsin more strongly (Ki = 6.3 x
      10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305254
TI  - [Gastric ulcers caused by post-burning stress: contribution of free radicals].
AB  - The purpose of this study was to analyse the blocking effect of superoxide
      dismutase (S.O.D.) at doses of 15.000 U.I. per kilogram (body weight), on the
      release of oxygen-derived free radicals, experimentally caused in the rat by
      burning 20% of the surface of its body, and its impact over macroscopic and
      microscopic lesions of the gastric mucosa. We used 48 rats divided into 5 groups.
      In groups 3 and 5 we provided S.O.D. i.v. immediately after the burn. All the
      animals had a catheter in their femoral vein for the administration of drugs.
      Morphologic data showed that 2 hours after the burn S.O.D. did not have any
      influence on the gastric injury; 5 hours after the burn, the morphologic damage
      of the gastric mucosa was less severe. The scavenging of the superoxide ion (free
      radical) by the superoxide dismutase may be responsible of the lower tissular
      damage of the gastric mucosa. These results confirm that a period of initial
      ischaemia may be an important etiopathogenic factor in severe lesions of the
      gastric mucosa after burns.

PMID- 8305255
TI  - [Complications of the intragastric balloon prosthesis].
AB  - The intragastric balloon prosthesis (PBIG) is being used as a mechanical
      treatment for obesity; an evaluation of its physiopathological implications,
      efficiency, and complications is still incomplete. In order to investigate in our
      area the incidence of complications of this endoscopic treatment, we have used
      the Danish model "Danish Obesity Treatment" (DOT) (Ballobes) inflated with air,
      in a prospective study in which forty obese patients were treated during three
      months. We draw the attention upon a gastric ulcer, a spontaneous anal extrusion
      migration, and a duodenal ulcer. We establish the safety of the method, the
      literature is reviewed, we discuss the cause and treatment of these lesions, and
      we conclude indicating the low morbidity and the absence of major complications
      such as oesophageal perforation or intestinal obstruction occurring with other
      prosthesis models.

PMID- 8305256
TI  - [Congenital hypertrophy of retinal pigment epithelium in familial colonic
      polyposis. Study of a family].
AB  - In the last years the relationship between congenital hypertrophy of retinal
      pigment epithelium (CHPRE) and familial adenomatous polyposis (FAP) has been
      described. It has been said that ophthalmoscopy would be a good screening method
      for following up the relatives of patients with FAP. We present an
      ophthalmoscopic study of 14 member of a family with FAP. Four members with FAP
      were operated on in our department. Only a six years-old child, to this date
      without FAP, presented CHPRE. We review the relationship between FAP and CHPRE,
      and emphasize the importance of follow-up in FAP specially when CHPRE is present.

PMID- 8305257
TI  - [Value of ultrasonography in the early diagnosis of hepatocellular carcinoma].
AB  - The size and the treatment of 135 hepatocellular carcinomas (HCC) has been
      analyzed, comparing patients diagnosed by a US screening program (group 1) and
      these diagnosed outside this program (group 2) to determine whether US screening
      on patients with chronic liver disease is able to diagnose (HCC) at an early
      stage. alpha-fetoprotein levels above 500 U/ml were considered as diagnostic.
      Twenty (46.5%) out of 43 patients from group 1 showed a HCC < 5 cm. vs. 14/92
      (15.2%) in group 2 (p = 0.001). Only 5.9% of the HCC < 5 cm. showed AFP > 500
      U/ml. vs. 29.7% of the advanced HCC (p = 0.003). 88.3% of patients of group 1 vs.
      63% of group 2 received specific treatment for HCC (p = 0.002). By means of US
      screening it is possible to diagnose HCC of smaller size and more susceptible to
      treatment. AFP is not useful in the early diagnosis of HCC.

PMID- 8305258
TI  - [Anatomopathologic and morphometric study of hepatocarcinoma].
AB  - Because of its great incidence and poor prognosis the hepatocarcinoma (HPC) has
      become a first line clinical challenge. This is the reason we have performed a
      descriptive anatomo-pathological analysis of our own cases and a study of the
      possible prognostic value of nuclear parameters. DESIGN: We have performed a
      retrospective study of 83 cases. We reviewed the clinical records and histologic
      preparations. METHODS: We analysed the following parameters: 1) Tumour site; 2)
      Association to cirrhosis; 3) Microscopic features (cellular type differentiation
      grade, peritumoral lymphocytic infiltration, architecture, mitotic index); 4)
      Metastatic frequency and location; 5) Morphometric nuclear parameters (area,
      perimeter, major diameter, major and minor axis, circle diameter, sphere volume,
      ellipse volume, shape factor. RESULTS: We highlight the following: 1) 50% of HPC
      associated to liver cirrhosis; 2) Ascites was more frequent in the tumours
      located in the right lobe or both lobes than in tumours affecting the left lobe
      (p < 0.005); 3) Macroscopically, the commonest type was the nodular one (47.8%);
      4) Microscopically, the commonest findings were as follows: cellular type (93%);
      differentiation grade type II (61.4%); trabecular architecture (64.9%);
      lymphocytic infiltration grade I (57.9%); 5) Mean mitotic index was 16.3 m./high
      power field. 6) There were distant metastases in 81.1% and portal vein invasion
      in 44.6%. 7) The nuclear morphometric study did not support any influence on
      patients' survival. CONCLUSIONS: 1) This descriptive analysis allows a
      morphological data base that is very useful for subsequent morphological or
      prognostic studies. 2) Our data do not support any influence of nuclear
      parameters on patients' survival, although we cannot exclude some relation in a
      greater series.

PMID- 8305259
TI  - Role of endoscopic retrograde cholangiopancreatography in liver transplantation.
AB  - Biliary tract complications develop in 5-10% of patients undergoing liver
      transplantation. They should be differentiated from other causes of graft
      dysfunction. The role of endoscopic retrograde cholangiopancreatography (ERCP) in
      the diagnosis and treatment of these patients is analyzed in a series of 116
      liver transplant patients. Nine patients (7.8%) were suspected to have biliary
      complications, and only four of them required immediate surgery because of early
      accidental T-tube removal and biliary tract stricture. The remaining five
      patients could be satisfactorily diagnosed and managed by ERCP which showed bile
      casts in the common bile duct in one case, and bile leaks in four cases, all of
      them being successfully resolved after endoscopic papillotomy. There were no
      complications related to the procedure. ERCP and endoscopic papillotomy is the
      technique of choice for diagnosis and treatment of biliary tract complications
      after liver transplantation.

PMID- 8305261
TI  - [AIDS as non-suspected cause of chronic diarrhea and malabsorption].
AB  - We report a case of chronic diarrhoea resulting in malabsorption syndrome in a
      patient with AIDS. Diarrhoea started two years before AIDS was diagnosed. The
      absence of risk factors may have delayed the diagnosis.

PMID- 8305260
TI  - [Non-steroid anti-inflammatory agents and digestive tract lesions].

PMID- 8305262
TI  - [Carcinoid tumor of the Vater's ampulla].
AB  - We report a patient with biliary obstruction of two years evolution. Blood
      chemistry evaluation was compatible with obstructive jaundice. Endoscopy and CT
      were suggestive of ampullary tumor. At laparotomy, the biopsy specimen was
      diagnosed as carcinoid tumor, and was treated by a Whipple's procedure.

PMID- 8305263
TI  - [Hematoma of the anterior rectus abdominis muscle associated with anticoagulant
      therapy].

PMID- 8305264
TI  - Duplex Doppler sonography and angiography in the evaluation for liver
      transplantation.
AB  - Duplex Doppler sonography (DDS) and angiography were performed in a prospective
      study comprising 22 adult patients with hepatic failure. The ability of the 2
      methods to visualize the different splanchnic vessels was compared, as well as
      any abnormality in the liver parenchyma and vessels. The purpose of the study was
      to decide if DDS could replace angiography in the pretransplantation work-up in
      these patients. The portal vein was correctly identified as open in 20 patients
      using DDS and in 21 patients at angiography. Portal vein thrombosis in one
      patient was correctly diagnosed by both methods. The identification of other
      vascular structures in the upper part of the abdomen, e.g., liver arteries and
      splenic vein, was demonstrated in 14 and 16 patients respectively at DDS.
      Hepatoma in one patient was correctly identified by both methods, as well as the
      presence of ascites. Splenic artery aneurysms were found in 4 patients at
      angiography, and in none of these was DDS able to show this abnormality. We
      conclude that abdominal angiography still seems superior to DDS in the evaluation
      of patients with hepatic failure prior to orthotopic liver transplantation,
      especially to demonstrate possible splenic artery aneurysms and detailed mapping
      of the hepatic arteries.

PMID- 8305265
TI  - Reversed diastolic blood flow at duplex Doppler. A sign of poor prognosis in
      renal transplants.
AB  - In 25 renal allografts out of 253 with graft dysfunction a reversed diastolic
      blood flow was observed at duplex ultrasonography during the first post
      transplant month. Eleven grafts were lost and 14 survived. The cause of graft
      loss was arterial thrombosis (n = 1), venous thrombosis or obstruction (n = 4),
      steroid resistant acute rejection (n = 4) and acute tubular necrosis (ATN) (n =
      2). The cause of graft dysfunction in the surviving grafts was ATN (n = 7) and
      acute allograft rejection (n = 7). Grafts with only peak-like or low velocity
      continuous diastolic flow reversal had a better prognosis (3 out of 15 were lost)
      than grafts with any other type of reversed flow pattern (8 out of 10 were lost).
      This difference was statistically significant (p < 0.01).

PMID- 8305266
TI  - Diffuse renal disease. Diagnosis by ultrasound-guided cutting needle biopsy.
AB  - The results of ultrasound (US)-guided renal parenchymal cutting needle biopsies
      in 101 consecutive patients were reviewed. The biopsies were done with the
      automated Biopty device mounted with a 2.0-mm needle. One or 2 needle passes
      yielded sufficient material for histologic analysis in 94% (95/101). Three or
      more passes were required in 6% (6/101) to obtain an adequate specimen.
      Mesangioproliferative glomerulonephritis, IgA-nephropathy, nephrosclerosis,
      diabetic nephropathy, secondary amyloidosis, lupus nephritis, minimal change
      glomerulonephritis and interstitial nephritis accounted for 79% of the final
      histologic diagnoses. The high quality and quantity of the tissue specimens
      yielded a definitive histologic diagnosis in renal parenchymal diseases of
      unknown etiology. Four major complications occurred, but no deaths or loss of
      kidney function were recorded. US proved useful as a guide to suitable biopsy
      site and in the detection of clinically significant complications. Prebiopsy
      screening of coagulation variables did not seem to prevent complications. Special
      attention should be paid to post-biopsy clinical observation.

PMID- 8305267
TI  - Cystic renal cell carcinoma. Imaging findings with pathologic correlation.
AB  - Twenty-seven cystic renal cell carcinomas (RCC) in 23 patients were analyzed
      radiologically and histologically. They were classified into 4 histopathologic
      growth patterns: a) multilocular (n = 15, 9 with macrocystic and 6 with
      microcystic components); b) unilocular (n = 3); c) cystic necrosis (n = 9); and
      d) tumors originating in the wall of a simple cyst (n = 0). Macrocystic
      multilocular RCC showed multiloculated configuration on ultrasound and contrast
      enhanced CT. Angiography revealed neovascularity peripherally or within the tumor
      (7/9 tumors). Microcystic multilocular RCC did not fulfill the criterion for a
      cystic mass on ultrasound: they were irregularly hyperechoic. There was little
      enhancement on postcontrast CT and only slight neovascularity on angiography.
      Unilocular RCC showed a cystic mass with an irregular wall or mural nodules on
      ultrasound and contrast enhanced CT. Necrotic RCC showed various sonographic
      findings from anechoic to irregular echoic. The appearance on CT varied from
      cystic with mural nodules to a multiloculated or irregular architecture.
      Neovascularity was seen in the periphery in 8 of 9 tumors. Clinically, this type
      seemed to be the most aggressive.

PMID- 8305268
TI  - Ultrasonography of thymoma with pathologic correlation.
AB  - Preoperative ultrasonograms of 11 surgically proved thymomas and ex vivo
      ultrasonograms of 3 resected specimens were compared with pathologic findings of
      resected specimens. Among 11 thymomas 7 appeared solid, 3 were solid with several
      cystic regions, and the remaining one was unilocular cystic in appearance. Cystic
      regions on ultrasonograms corresponded to cystic changes on pathologic specimens.
      Six malignant thymomas showed a typical lacy appearance on ultrasonograms, which
      corresponded to the lobulated configuration separated by fibrous septa shown on
      the pathologic specimens.

PMID- 8305269
TI  - Simultaneous videoradiography and computerized pharyngeal manometry-
      videomanometry.
AB  - To obtain more information about muscle function in patients with dysphagia,
      simultaneous barium swallow and computerized pharyngeal manometry with solid
      state pressure transducers was employed for the evaluation of the pharynx and the
      pharyngoesophageal segment (PES) in 30 consecutive patients. The manometry
      catheter was positioned under fluoroscopic control, providing localized
      measurements of the intraluminal pressures in the pharynx. Sixteen patients had a
      normal barium swallow. In 5 (31%) of these the manometry disclosed PES
      dysfunction, i.e. increased resting pressures between swallows in 3 patients
      (mean 120 +/- 13 mm Hg), and increased contraction pressures during peristalsis
      in 2 (mean 297 +/- 21 mm Hg). Barium swallow and manometry are complementary: the
      former reflecting transport through the pharynx and penetration to the airways,
      the latter the intraluminal pressures created by the pharyngeal wall. The
      combination of barium swallow and manometry gives information about pressure in
      relation to bolus transport, which may elucidate pharyngeal dysfunction.

PMID- 8305270
TI  - Diagnosis of ganglions in the hand and wrist by sonography.
AB  - In the practice of hand surgery, imaging of soft tissue structures can provide
      useful information for diagnosis and preoperative planning. Sonography with high
      frequency technique giving high spatial resolution is especially rewarding. In a
      joint project of the Departments of Radiology and Hand Surgery we evaluated the
      diagnostic accuracy and clinical value of sonographic assessment of ganglions of
      the hand and wrist. The material comprises 68 soft tissue lesions clinically
      suspected to be ganglions. Sonography revealed a ganglion in 53 cases, 34 of
      which went to surgery. The diagnosis was confirmed in every case. One collapsed
      ganglion was missed. Nonpalpable ganglions causing clinical symptoms could be
      demonstrated, and a suspected ganglion could sometimes be ruled out in favor of
      other diagnoses. Sonography could delineate the entire ganglion and often its
      connection with the joint space.

PMID- 8305271
TI  - Posttraumatic osteolysis of the pubic bone simulating malignancy.
AB  - Posttraumatic osteolysis (PO) of the os pubis is a diagnostic entity
      characterized at radiography by rapidly progressing destructive changes in
      fractures of the pubic body or rami. Fourteen patients with PO are here reported
      of whom in 8 the radiographic course of the condition was followed. They were all
      post-menopausal women and 7 were predisposed to osteopenia. The primary fractures
      were related to mild trauma in 7 patients and 7 had insufficiency fractures. Four
      patients had bilateral symmetrical PO. All 14 patients had concomitant
      insufficiency fractures of the sacrum observed at radiography, CT, scintigraphy
      or MR, probably due to pelvic instability caused by the PO of the os pubis.
      Symptoms of the sacral fractures usually dominated the clinical condition. Bony
      healing of the PO did not occur in any of the patients, but in all 8 patients
      followed radiographically, the fractures of the sacrum healed clinically and at
      CT. Knowledge about the condition is important to avoid unnecessary biopsy of the
      PO considered a metastatic lesion and/or extensive diagnostic search for a
      primary tumor.

PMID- 8305272
TI  - Dual photon absorptiometry for bone mineral measurements using a gamma camera.
AB  - A gamma camera was equipped with a special collimator and arm assembly for bone
      mineral measurements with dual photon absorptiometry (DPA). The system was
      evaluated in vitro and in vivo and compared both with a rectilinear DPA and a
      dual energy X-ray (DEXA) system. All 3 systems showed a linear response in
      measurements of 4 vials, containing different amounts of hydroxyapatite. Phantom
      measurements with the gamma camera system showed a precision of 1.6% to 2.8%.
      Results obtained in 8 healthy volunteers with rectilinear and gamma camera
      systems were well correlated (R2 = 0.78). With the photon beam directed from
      posterior to anterior, the separation of vertebrae was easy with the gamma camera
      system. We conclude that bone mineral measurements can be made with a gamma
      camera for assessment of fracture risk and in the decision process whether a
      patient needs treatment or not. For follow-up, the precision of DPA with a gamma
      camera is inadequate.

PMID- 8305273
TI  - Distribution and dosimetry of 111In DTPA-D-Phe-octreotide in man assessed by
      whole body scintigraphy.
AB  - The distribution and dosimetry of the somatostatin analog 111In-DTPA-octreotide
      was evaluated in 6 patients. Whole body scintigraphy in anterior and posterior
      projections was performed 0.5, 5, 24 and 48 hours after injection. Region-of
      interest analysis for different organs and the whole body was used to determine
      111In octreotide half-life-corrected uptake in absolute and relative terms. A
      rapid initial uptake was seen in the kidneys (2-7%), the spleen (2-6%) and in the
      liver (4-8%). A lower uptake was seen in the pituitary gland (maximum 0.3%), the
      thyroid (maximum 0.07%), in the female breast (maximum 1.2%), in the urinary
      bladder and in the intestinal tract. The elimination pattern varied between
      different organs. The effective dose equivalent was evaluated to be in the range
      0.08 to 0.13 mSv/MBq (average 0.10 mSv/MBq). The behavior of 111In-DTPA
      octreotide suggests follow-up scintigraphy in a period extending up to at least
      24 hours after injection.

PMID- 8305274
TI  - Sister chromatid exchanges in cultured amniocytes exposed to diagnostic
      ultrasound in vitro.
AB  - An in vitro system has been set up to study the possible genetic effects of
      diagnostic ultrasound (US) on the developing fetus. Amniotic cells were cultured
      by the in situ technique. Well established clones were exposed to US for various
      lengths of time using a linear array transducer within a sound transparent
      apparatus. Cells were then grown in the presence of 5-bromo-2'-deoxyuridine and
      processed for scoring the number of sister chromatid exchanges (SCE) as the
      cytogenetic endpoint. There was no linear relationship between the SCE frequency
      and the duration of US exposure. Variance analysis showed that only
      interindividual variability was a significant component of total variation.
      Neither the main effect of treatment nor the interaction effect were
      statistically significant. The data suggest that US delivered from a diagnostic
      unit to actively growing cultured fetal cells in a system closely mimicking the
      conditions of US exposure during amniocentesis does not induce SCE.

PMID- 8305275
TI  - Ultrasound monitored laser-induced local hyperthermia in the liver. An
      experimental study on pigs.
AB  - Ultrasound (US) was used to monitor the size of tissue necrosis generated by Nd
      YAG laser-induced local interstitial hyperthermia and tissue coagulation in 8
      normal pig livers. Four treatments were done in each liver with 4 different
      energy settings. The size of the tissue necrosis measured on specimens was
      compared to the size measured on US. The laser energy caused a round tissue
      necrosis with some charring in the centre surrounded by a zone of white necrosis
      and a thin border of hyperaemia. A good correlation was found between the true
      and US-measured size of the necrosis diameters. It therefore seems possible to
      safely guide and monitor local laser hyperthermia in the liver with real-time US.
      The water-cooled quartz fibre used in this study has, however, some limitations.

PMID- 8305276
TI  - Contrast radiography in small bowel obstruction. A randomized trial of barium
      sulfate and a nonionic low-osmolar contrast medium.
AB  - Thirty-six adult patients clinically suspected of small bowel obstruction
      underwent small bowel contrast radiography with either barium sulfate or a
      nonionic low-osmolar contrast medium after randomization. Films were taken after
      2, 4, and 8 hours and later when needed. No difference as regards visualization
      and diagnostic quality was found between the 2 media. It is concluded that a
      nonionic low-osmolar contrast medium is an alternative to barium sulfate for
      small bowel contrast radiography where small bowel obstruction is suspected.

PMID- 8305277
TI  - MR imaging of pituitary region lesions with gadodiamide injection.
AB  - Twelve patients with known or suspected pituitary lesions underwent MR imaging
      with gadodiamide injection at a dose of 0.1 (n = 5) or 0.3 (n = 7) mM/kg. Six of
      the patients were also studied with 0.1 mM/kg gadopentetate dimeglumine.
      Consistent with previous reports gadodiamide injection was found to be a safe and
      effective contrast medium for MR imaging of the pituitary region. No additional
      diagnostic information was obtained using 0.3 mM/kg gadodiamide injection
      compared to 0.1 mM/kg gadopentate dimeglumine in the same patients. The high dose
      (0.3 mM/kg) gadodiamide injection in 7 patients did not shorten the T2 value
      sufficiently to overwhelm the T1 shortening and leave pathologic lesions
      hypointense compared to precontrast studies. With the comparable relaxivities of
      gadodiamide injection and gadopentetate dimeglumine, similarities in results have
      to be expected when using these media for MR image enhancement.

PMID- 8305278
TI  - Interaction between beta-blockers and contrast media during intracoronary
      administration in rabbit heart.
AB  - The effects of ionic, meglumine sodium diatrizoate (Urografin 76) and nonionic,
      iohexol contrast media were examined in the absence and presence of propranolol,
      a beta-blocker having nonspecific membrane stabilizing action and atenolol, a
      beta-blocker lacking nonspecific membrane stabilizing action on Langendorff
      perfused rabbit hearts. Contrast medium, 0.7 ml, was injected into the aortic
      root in the absence and presence of 10(-7) and 10(-5) M beta-blocker to observe
      the changes in resting tension, force of contraction, rate of contraction, heart
      rate and PR interval. Beta-blockers and contrast media interact in affecting
      myocardial contractility, heart rate and atrioventricular conduction. The
      interaction is milder when the beta-blocker lacks membrane stabilizing activity
      and the contrast medium is nonionic.

PMID- 8305279
TI  - Cardiac effects of coronary arteriography with electrolyte addition to iohexol. A
      study in dogs with and without heart failure.
AB  - Electrolyte addition to nonionic contrast media has been suggested to further
      reduce the incidence of ventricular fibrillation during coronary arteriography.
      The present study was designed to investigate the effects of adding 30 mM NaCl,
      0.9 mM KCl, 0.15 mM CaCl2 and 0.1 mM MgCl2 to iohexol on cardiac
      electrophysiology and hemodynamics (iohexol+electrolytes = IPE). Contrast media
      were injected into the left main coronary artery in 9 open-chest, anesthetized
      dogs before and after induction of acute ischemic heart failure. IPE increased
      left ventricular inotropy (LV dP/dtmax) with no initial decrease, even during
      heart failure. During heart failure IPE induced the same hemodynamic effects as
      iohexol without electrolyte addition. IPE slightly lengthened epicardial
      monophasic action potential duration before heart failure. We conclude that IPE
      appears to be well tolerated hemodynamically. The electrophysiologic differences
      between IPE and iohexol are small when the injection time is not longer than 5 s.

PMID- 8305280
TI  - Effect of iodinated contrast media on ionic calcium.
AB  - This study was conducted to characterize the alterations in serum ionized calcium
      induced by contrast media (CM) and to determine the cause of the change. Fresh
      human blood samples as well as an electrolyte solution (ES) containing 1.2 mM
      calcium ions were diluted with CM and alterations in ionized calcium were
      measured using an electrometer. The CM tested were diatrizoate, iopamidol,
      iohexol, ioxaglate, isotonic saline, Na2-Ca-EDTA and pure meglumine. When CM were
      mixed with blood, ionic CM produced a greater decrease in ionized calcium than
      nonionic CM or saline. When mixed with ES, a significant reduction of ionized
      calcium was induced by ioxaglate and diatrizoate in comparison with saline. Na2
      Ca-EDTA and meglumine caused no reduction in ionized calcium. Ioxaglate and
      diatrizoate caused calcium binding due to anions; binding induced by the latter
      was more prominent than that by the former. These observations suggest that a
      nonionic CM is more desirable for coronary arteriography of high-risk patients.

PMID- 8305281
TI  - Three-dimensional display of liver, spleen, hepatoma, and blood vessels by MR
      imaging and computer graphics.
AB  - The technique of generating 3-D images from CT and MR data has made progress.
      Manipulation of the images has become simpler, the processing time shorter, and
      the quality better. Clinical application of this technique has been performed for
      images of brain (5, 7, 8) and bone (1, 2, 6), but only a few studies have been
      done of abdominal organs (3, 4).

PMID- 8305282
TI  - Fracture of the occipital condyle as an incidental finding during CT-evaluation
      of a maxillary fracture.
AB  - A 43-year-old male presented with blunt facial trauma after a motor-vehicle
      accident. CT-evaluation revealed a right-sided maxillary fracture and a fracture
      of the left occipital condyle. The fracture of the occipital condyle is
      potentially unstable and fatal cases have been described. Plain radiographs are
      not diagnostic. This occipital condyle fracture was an incidental finding during
      CT-evaluation of a maxillary fracture and is probably the first case with
      coronary CT scans of this type of fracture.

PMID- 8305283
TI  - Commonly used chiral drugs: a survey.
AB  - Initial results of a comparative survey of commonly used chiral drugs are
      presented. The survey considered the differences between drugs used in 1982 with
      those in use in 1991. Two major conclusions were reached: the use of single
      isomer chiral drugs had increased from 31.1% in 1982 to 34.3% in 1991 and the
      proportion of synthetic single isomer chiral drugs available in 1991 was
      considerably greater than in 1982.

PMID- 8305284
TI  - Use of isotopically chiral [4'-13C]famciclovir and 13C NMR to identify the chiral
      monoacetylated intermediates in the conversion of famciclovir to penciclovir by
      human intestinal wall extract.
AB  - Famciclovir is the oral form of the potent antiherpesvirus agent, penciclovir.
      Hydrolysis of one of the acetyl ester groups of famciclovir creates a chiral
      centre leading to the possible formation of (R)- and (S)-enantiomers. During its
      conversion to penciclovir, famciclovir forms two chiral metabolites, namely
      monoacetyl-6-deoxy-penciclovir and monoacetyl-penciclovir. The absolute
      configuration and stereospecificity of the monoacetyl metabolites of famciclovir,
      produced in human intestinal wall extract, were determined using isotopically
      chiral famciclovir and 13C NMR spectroscopy of the isolated metabolites. 13C NMR
      showed that the esterase(s), in human intestinal wall extract, hydrolysed the
      acetyl group preferentially from the pro-(S)-acetoxymethyl group of famciclovir.
      The specificity of esterase action in forming monoacetyl-6-deoxy-penciclovir and
      monoacetyl-penciclovir was about 77 and 72%, respectively.

PMID- 8305285
TI  - Use of isotopically chiral [4'-13C]penciclovir and 13C NMR to determine the
      specificity and absolute configuration of penciclovir phosphate esters formed in
      HSV-1 and HSV-2 infected cells and by HSV-1-encoded thymidine kinase.
AB  - Penciclovir is a potent antiherpesvirus agent which is highly selective due to
      its phosphorylation only in virus infected cells. Phosphorylation of one of the
      hydroxymethyl groups of penciclovir (PCV) creates a chiral centre leading to the
      possible formation of (R)- and (S)-enantiomers. The absolute configuration and
      stereospecificity of the PCV-phosphates produced in cells infected with herpes
      simplex viruses types 1 and 2 (HSV-1 and HSV-2), as well as by HSV-1-encoded
      thymidine kinase, were determined using isotopically chiral [4'-13C]PCV
      precursors and 13C NMR spectroscopy of the isolated metabolites. The absolute
      configuration of penciclovir-triphosphate (PCV-TP) produced in HSV-1 infected
      cells was shown to be S with an enantiomeric purity of greater than 95%. However,
      in contrast fo HSV-1-infected cells in which none of the (R) enantiomer was
      detected, about 10% of (R)-PCV-TP was produced in HSV-2-infected cells.
      Phosphorylation of PCV by HSV-1-encoded thymidine kinase was found to give 75%
      (S)- and 25% (R)-PCV-monophosphate. The proportion of the (S)-isomer appears to
      be amplified in the subsequent phosphorylations leading to the triphosphate.

PMID- 8305286
TI  - Stereoselective cyclooxygenase inhibition in cellular models by the enantiomers
      of ketoprofen.
AB  - The pharmacological activity of rac-ketoprofen and its enantiomers was
      investigated in vitro using different cellular models. The effect of these
      compounds on arachidonic acid metabolism was assessed by measuring the inhibition
      of prostanoid generation under the action of several agonists. Thus, we have
      evaluated the inhibition of (1) thromboxane B2 synthesis in rabbit platelets and
      human polymorphonuclear leukocytes (PMNs), (2) prostaglandin E2 synthesis in
      three cultured cells, namely human umbilical vein endothelial cells (HUVEC),
      human keratinocytes, and mouse macrophage-like P388D1 cells. The IC50 values
      found for (+)-(S)-ketoprofen were in the range between 0.1 nM and 0.8 microM,
      being slightly lower in all models than those found for rac-ketoprofen (0.4 nM-3
      microM). On the other hand (-)-(R)-ketoprofen showed inhibition of cyclooxygenase
      only at concentrations two or three orders of magnitude higher than those
      required for the (+)-(S) enantiomer. These results, obtained with cell types of
      relevance for inflammatory processes and with compounds of high optical purity,
      demonstrate that the prostanoid biosynthesis inhibition caused by the drug rac
      ketoprofen is exclusively due to its dextrorotatory enantiomer.

PMID- 8305287
TI  - Microbial metabolism of 2-arylpropionic acids: chiral inversion of ibuprofen and
      2-phenylpropionic acid.
AB  - The metabolism of (R,S)-ibuprofen has been investigated in 24 microbial cultures.
      Of these Cunninghamella elegans, Mucor hiemalis, and Verticillium lecanii
      catalyzed the oxidation of the drug to 2-[4-(2-hydroxy-2
      methylpropyl)phenyl]propionic acid, a known mammalian metabolite. The extent of
      metabolism was greatest with V. lecanii, with some 47% of the substrate being
      consumed over a 7-day incubation period. Enantiomeric analysis indicated
      stereoselective metabolism of (R)-ibuprofen, the enantiomeric composition of the
      residual substrate being R/S = 0.25. Following a preparative scale incubation of
      (R,S)-ibuprofen with V. lecanii, in which the reaction was allowed to go to
      completion, the metabolite was found to be predominantly of the S-configuration
      (S/R = 2.1), suggesting that chiral inversion of either the drug and/or the
      metabolite had taken place. Analysis of extracts following incubation of (R,S)-,
      (R)-, and (S)-2-phenylpropionic acid with V. lecanii, for 21 days, indicated that
      chiral inversion of the (R)-enantiomer to its optical antipode had taken place.
      The results of these investigations indicate that microorganisms, in addition to
      mammals, are able to mediate the chiral inversion of 2-arylpropionic acids. This
      observation may have implications for the preparation of optically pure 2
      arylpropionic acids.

PMID- 8305288
TI  - Stereoselective sulfate conjugation of isoproterenol in humans: comparison of
      hepatic, intestinal, and platelet activity.
AB  - The stereochemistry of sulfate conjugation of isoproterenol (ISO) was examined
      with human liver, intestine, and platelets as the phenolsulfotransferase (PST)
      enzyme source and PAP35S as the cosubstrate. With the hepatic cytosol, two
      distinct sulfation reactions were identified, a high affinity reaction (Km 5 to
      50 microM) and a low affinity reaction (Km 360 to 2,900 microM). The efficiency
      of sulfation (Vmax/Km) for both reactions was 5-fold higher for (+)- than for (-)
      ISO. When the hepatic PSTs were resolved by ion-exchange chromatography, it could
      be shown that the high affinity reaction was catalyzed by the monoamine (M) form
      and the low affinity reaction by the phenol (P) form of PST. Only the high
      affinity (M form) sulfation was detected in the jejunal cytosol with a Vmax/Km
      value 6.1-fold higher for (+)- than for (-)-ISO. Finally the platelet, as a
      potentially useful model tissue, also demonstrated only the high affinity M form
      reaction with a Vmax/Km value 5.7-fold higher for (+)- than for (-)-ISO. In
      summary, this study has shown that sulfation of ISO by PSTs in various human
      tissues is stereoselective and favors the inactive (+)-enantiomer over the active
      (-)-enantiomer by about 5-fold, a finding which should be considered in the
      therapeutic use of chiral drugs cleared by sulfate conjugation.

PMID- 8305289
TI  - Warfarin metabolites: stereochemical aspects of protein binding and displacement
      by phenylbutazone.
AB  - The in vitro human serum albumin binding characteristics of the enantiomers of
      the major metabolites of warfarin [6-hydroxywarfarin (6-HW), 7-hydroxywarfarin (7
      HW), (S)-warfarin alcohols [(S,S)- and (S,R)-WA], and (R,S)-warfarin alcohol
      [(R,S)-WA]] have been studied, using a stereospecific HPLC assay. Warfarin
      metabolites are less bound both within plasma and a 40 g/liter solution of human
      serum albumin than the enantiomers of warfarin. The reduced warfarin metabolites
      have a lower fraction unbound [1.33% for (S,R)-WA, 2.09% for (S,S)-WA, and 1.04%
      for (R,S)-WA] than hydroxylated metabolites [3.24% for (R)-6-HW, 4.26% (S)-6-HW,
      4.49% for (R)-7-HW and 4.27% for (S)-7-HW] to HSA. Phenylbutazone produced a
      concentration-dependent increase in the unbound fraction of all metabolites. It
      was possible to predict the unbound fraction of warfarin metabolites based on the
      unbound fraction of warfarin enantiomers.

PMID- 8305290
TI  - Mortality profiles based on living conditions: a Venezuelan experience.

PMID- 8305291
TI  - PAHO advisory: Aedes albopictus in the Caribbean.

PMID- 8305292
TI  - Expanded programme on immunization. Elimination of neonatal tetanus.

PMID- 8305293
TI  - Zoonoses. Country report.

PMID- 8305294
TI  - Control of tuberculosis transmission in health care settings. A joint statement
      of the WHO Tuberculosis Programme and the International Union Against
      Tuberculosis and Lung Disease (IUATLD).

PMID- 8305295
TI  - Global programme on AIDS. AIDS surveillance in the WHO Western Pacific Region.

PMID- 8305296
TI  - Malaria chemoprophylaxis regimens for travellers.

PMID- 8305297
TI  - A case of extramammary Paget's disease with depigmented macules as the sole
      manifestation.
AB  - We report a 76-year-old man who had four depigmented macules in the genital area
      as the sole manifestation of extramammary Paget's disease (EMP). Histologically,
      many scattered, dissociated, plump Paget cells, and small intraepidermal nests of
      these cells were seen in all four lesions. The distribution of Paget cells
      extended beyond the margin of the depigmented areas into adjacent normally
      pigmented skin. Fontana-Masson staining revealed a reduction in, or absence of,
      melanin deposition along the basal layer of the depigmented lesions, in contrast
      with an abundance of melanin along the basal layer of the adjacent normal skin.
      Pigment-blockade melanocytes and melanophages were seen within or below the
      affected epidermis. The depigmentation in this case could have been caused by a
      symbiotic disorder between melanocytes and keratinocytes (including melanocyte
      destruction), and by a disorder in melanosome transmission to the keratinocytes.
      This case illustrates that a depigmented macule may be a diagnostic feature of
      EMP. Moreover, depigmentation is probably one of the earliest clinical features
      of EMP, and not a neighbouring secondary change such as occurs in the Sutton's
      halo naevus phenomenon.

PMID- 8305298
TI  - What is segmental neurofibromatosis?
AB  - Two unrelated children with von Recklinghausen's neurofibromatosis (NF1) had
      mothers with cutaneous NF1 lesions in a limited distribution. The cutaneous
      pattern in the mother of case 1 was clearly segmental, and probably represents
      mosaicism for the NF1 mutation which was passed on to the child. In the second
      case the distribution in the mother was less obviously segmental, but may still
      represent mosaicism. It is more difficult to diagnose mosaicism for NF1 in
      individuals with no affected offspring, or with more limited cutaneous
      manifestations. The difficulties in defining segmental NF and assigning a genetic
      risk are discussed.

PMID- 8305299
TI  - Cutaneous manifestations of mycobacterial infection in patients with AIDS.

PMID- 8305300
TI  - Autosomal recessive epidermolysis bullosa simplex. A case report.
AB  - We report a male child with autosomal recessive epidermolysis bullosa simplex
      presenting at birth. The patient subsequently developed cutaneous atrophy, nail
      dystrophy, milia and alopecia. He had growth retardation and anaemia, but there
      were no other associated abnormalities. Electron microscopy showed epidermolytic
      cleavage. The family history indicated an autosomal recessive mode of
      inheritance.

PMID- 8305301
TI  - Cutaneous sarcoid-like granulomas in primary immunodeficiency disorders.
AB  - We report the occurrence of cutaneous sarcoid-like granulomas in one patient with
      common variable immunodeficiency and another with 'thymoma and
      hypogammaglobulinaemia'. To our knowledge, this is the first time that such skin
      lesions have been described in patients with primary immunodeficiency. These
      granulomas may be attributed to a combination of interleukin-2 deficiency and a
      profound CD4 lymphopenia. The lesions are similar to the non-infectious 'papular
      eruption' associated with human immunodeficiency virus infection, and might
      reflect a common pathogenic mechanism.

PMID- 8305302
TI  - Progesterone-induced urticaria: response to buserelin.
AB  - We report a 41-year-old Caucasian woman with polycystic liver and kidney disease,
      and a 9-year history of severe cyclical urticaria related to her menses. The
      urticaria was not adequately controlled by antihistamines or Prempak-C
      (conjugated oestrogens and norgestrel). Intradermal testing with progesterone was
      strongly positive at 30 min and 18 h. Buserelin, administered intranasally at
      doses of up to 800 micrograms daily, controlled the urticaria within 4 weeks, and
      she was completely symptom-free thereafter. She had therapy-induced amenorrhoea
      and occasional hot flushes. Unfortunately, her liver cysts progressively
      enlarged, and a right hepatectomy was performed in June 1992, but she died after
      complications 3 weeks later. Prior to this she had been free of urticaria for 6
      months after starting buserelin. Buserelin, a gonadotrophin-releasing hormone
      analogue, may be useful in the management of progesterone-induced urticaria, in
      patients in whom conjugated oestrogens are contraindicated or unhelpful.

PMID- 8305303
TI  - Juvenile pemphigoid nodularis.

PMID- 8305304
TI  - Darier's sign associated with non-Hodgkin's lymphoma.

PMID- 8305305
TI  - In vitro release of granulocyte/macrophage colony-stimulating factor from
      peripheral blood mononuclear cells of atopic dermatitis patients in response to
      stimulation with dust mite antigen.

PMID- 8305306
TI  - Cytokine profile of patients with bullous pemphigoid.

PMID- 8305307
TI  - Linear IgA dermatosis related to vancomycin.

PMID- 8305308
TI  - Oral lichen planus in childhood.

PMID- 8305309
TI  - Need for histopathological examination of skin cysts.

PMID- 8305310
TI  - Sustained benefit of interferon-alpha therapy and oral hyposensitization in
      severe atopic dermatitis.

PMID- 8305311
TI  - Butchers' warts: no evidence for person to person transmission of HPV7.
AB  - The distribution of warts due to HPV7 in workers in six abattoirs and 103 retail
      and wholesale butcheries has been studied to determine whether the high
      prevalence of HPV7 in the meat trade is the result of enhanced person to person
      transmission, or whether it is a ubiquitous virus which is activated by an
      unknown factor in meat. Warts were detected in 164 of 486 men. Scrapings were
      taken from 156 men, and HPV DNA was found in 112 samples, 74 of which contained
      HPV7. HPV7 was found in 36 workplaces, and there was no evidence of clustering of
      cases, as would be expected if person to person transmission was occurring in the
      workplace. This suggests that HPV7 is widely distributed in the community, but
      only causes clinical disease under specific conditions. We suggest that some
      unknown factor in meat enhances viral replication.

PMID- 8305312
TI  - Quantitative in vitro assessment of N-alkyl sulphate-induced cytotoxicity in
      human keratinocytes (HaCaT). Comparison with in vivo human irritation tests.
AB  - A spontaneously immortalized human keratinocyte line, HaCaT, was used as an in
      vitro model to predict the cutaneous irritation of anionic surfactants. For this
      purpose, a number of sodium salts of N-alkyl sulphates with hydrocarbon chain
      lengths varying between C8 and C16 were studied for possible cytotoxic effects.
      The endpoints used to assess toxicity were uptake of the vital dye neutral red
      (NR) and cell morphology criteria 24 h after dosing. A linear proportionality
      between keratinocyte number and NR uptake was established. All tested surfactants
      had cytotoxic effects as demonstrated by a decreased NR uptake, which showed a
      clear dose-response relationship. Concentrations resulting in 50% inhibition of
      NR uptake (IC-50) ranged from 0.15 mmol (sodium lauryl sulphate, C12) to 1.23
      mmol (sodium octyl sulphate, C8). The in vitro cytotoxicity data were highly
      reproducible when the test was repeated after several weeks. The cytotoxicity
      data from these assays were compared with the irritant responses (as evaluated by
      measurement of erythema and transepidermal water loss) obtained after 24 h
      application of the same compounds (300 microliters of 20 mmol aqueous solution)
      to the volar forearm of human volunteers. There were significant linear
      correlations between the IC-50 values and both barrier damage (transepidermal
      water loss) and erythema (as evaluated by skin colour reflectance measurements).
      For the test substances, however, the sensitivity of the in vitro system was
      between 10 and 100 times higher than that observed in human skin in
      vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305313
TI  - Electrical impedance compared with other non-invasive bioengineering techniques
      and visual scoring for detection of irritation in human skin.
AB  - A new, non-invasive device, which enables local measurements of electrical
      impedance to a controlled depth, has been used to evaluate the degree of
      irritation in human skin. The results have been compared with those obtained
      using other non-invasive techniques, i.e. with transepidermal water loss (TEWL),
      electrical capacitance moist measurement (ECM), laser-Doppler flowmetry (LDF),
      and visual scoring. Sodium lauryl sulphate solutions (0.1-5.0%), and a blank,
      were applied in Finn Chambers for 24 h on the volar forearm of 10 healthy
      volunteers. Values were recorded before application of the test chambers, and at
      1 h, 24 h, 1 week and 2 weeks after removal. Thus, both the degree of initial
      damage and the healing process were monitored. There was close agreement among
      values obtained using electrical impedance, TEWL and visual readings. Results
      obtained using ECM and LDF were not consistent with the other three methods. In
      evaluating irritation of the skin, the practical situation may influence the
      choice of bioengineering tools. In most circumstances, a combination of methods
      would be preferable.

PMID- 8305314
TI  - A comparative study of the frictional properties of emollient bath additives
      using porcine skin.
AB  - The coefficient of friction of 14 prescribable bath emollients was determined
      using porcine skin attached to a loaded plunger placed through a bearing in a
      friction-measuring carriage, held above a reciprocating table powered by a DC
      motor. The carriage was mounted in low-friction rollers, and restrained by a
      piezo-electric force transducer connected to an amplifier and recorder. Friction
      was measured at room temperature, and at 45 degrees C. Emulsifying ointment and
      Bath E45 had the highest coefficients of friction, at room temperature and 45
      degrees C, respectively, and Emmolate and Hydromol had the lowest. Nine of the 14
      emollients had a lower coefficient of friction at 45 degrees C, one had a
      coefficient of friction which was the same at both temperatures, and four had a
      coefficient of friction which was higher at 45 degrees C.

PMID- 8305315
TI  - Contact allergy to corticosteroids: the results of a two-centre study.
AB  - We report a comparative study of the patch-test results obtained with a
      corticosteroid series, added to the standard series, in two centres, one in
      Belgium and the other in the Netherlands. The frequencies of positive reactions
      to the corticosteroids differed considerably between the two centres, and we
      suggest several reasons for this.

PMID- 8305316
TI  - An evaluation of the revised seven-point checklist for the early diagnosis of
      cutaneous malignant melanoma.
AB  - The seven-point checklist has been widely advocated as a sensitive screening test
      for malignant melanoma. A number of groups have questioned the sensitivity of
      this system, especially in the detection of early lesions. We have assessed the
      sensitivity and specificity of the revised seven-point checklist when applied to
      lesions seen in our department over a 26-month period and compared it with the
      American ABCDE evaluation system. All melanomas (n = 65) were detected using the
      revised seven-point checklist and all were found to have at least one of the
      three major criteria defined by that system. Five (7.7%) melanomas were not
      picked up by the ABCDE checklist. Of 100 randomly selected patients who attended
      the clinic during the same period, with clinically diagnosed benign pigmented
      lesions, 63 had at least one major feature of the revised seven-point checklist.
      Forty (62%) of the melanomas, compared with only (4%) of the benign lesions, had
      more than one major feature. This study confirms the sensitivity of the revised
      seven-point checklist in the diagnosis of cutaneous malignant melanoma.

PMID- 8305317
TI  - Reliability of naevus counts in identifying individuals at high risk of malignant
      melanoma.
AB  - The majority of deaths from malignant melanoma could be prevented by regular
      screening of at-risk individuals. However, the feasibility of introducing active
      screening programmes depends on the reliability of criteria for identifying those
      individuals who are at increased risk. Several case-control studies indicate that
      one of the most important risk factors is the number of benign pigmented naevi.
      This criterion might constitute a practical means of identifying individuals
      suitable for inclusion in an active screening programme. The aim of this study
      was to assess the reliability of using naevus counts as an indicator of risk. Two
      possible methods of assessment were compared: assessment by trained interviewers,
      and assessment by experienced dermatologists. The results suggest that this
      criterion may not be as practical or reliable as originally anticipated.
      Interviewer naevus counts correlated poorly with dermatologists' assessments
      (kappa = 0.19). Counts by dermatologists of the number of naevi on the left arm
      differed by up to nine naevi, although most counts were within four naevi of each
      other. There was reasonable correlation between naevus counts on the left arm and
      those on the whole body (r = 0.71). However, the relationship was not perfect.
      Selection of individuals for screening solely based on the number of naevi on the
      left arm may exclude many people with high total body counts but relatively low
      left arm counts.

PMID- 8305318
TI  - Profile of the malignant melanoma excised in general practice.
AB  - An analysis of 27 malignant melanomas diagnosed in a Dutch laboratory
      specializing in the provision of a cytology and pathology service to general
      practitioners is reported. The median age of the patients was 39 years, and was
      lower in women (30 years) than in men (54 years). In the national data the mean
      age was 52 years for both sexes. There were twice as many women as men. There
      were no tumours from the head and neck region. The ratio of tumours on the limbs
      to those on the trunk was 3:2. The melanomas were very small (74% with a diameter
      of < or = 6.0 mm), and they were also very thin (74% with a Breslow thickness <
      or = 1.0 mm), compared with the national data in which 62% were < or = 1.0 mm.
      Not surprisingly, the estimated mean 5-year survival was favourable (95% for
      women and 76% for men). After a period of follow-up ranging from 2 to 32 months,
      none of the patients had any evidence of residual disease. This study
      demonstrates that in skin biopsies performed by general practitioners melanomas
      are mainly detected by chance, and have a very good prognosis.

PMID- 8305319
TI  - Polymorphic light eruption: prevalence in Australia and England.
AB  - The prevalence and clinical characteristics of polymorphic light eruption were
      assessed by a questionnaire survey of 172, 196 and 182 subjects in Perth,
      Ballarat and London, respectively. The prevalence was 5.2% in Perth (latitude 32
      degrees), 3.6% in Ballarat (37.5 degrees) and 14.8% in London (51.5 degrees). The
      age distribution (mostly first three decades) and male:female ratio (1:3) was
      similar for affected individuals in all three areas. Development of tolerance
      during the summer was more common in Perth (66.7%) and Ballarat (71.4%) than in
      London (40.7%).

PMID- 8305320
TI  - Haemorrhagic cellulitis: a syndrome associated with tumour necrosis factor-alpha.
AB  - A newly defined clinical syndrome, haemorrhagic cellulitis, is described in 12
      patients. The syndrome consists of an acute onset of extremely painful erythema
      affecting dependent areas, followed by dermal haemorrhage and sloughing of the
      overlying epidermis, and requiring both antibiotics and systemic corticosteroids
      for complete resolution. The patients usually have demonstrable Gram-negative or
      Gram-positive infection, of non-cutaneous origin, and underlying systemic
      disease. Vacuolopathic necrosis of epidermal keratinocytes, and damaged vascular
      endothelium of the dermal blood vessels can be demonstrated by light and electron
      microscopy, as well as by lectin studies. Immunocytochemical studies reveal the
      presence of activated macrophages and T lymphocytes. We believe the syndrome is
      due to lipopolysaccharide-induced or bacterial mitogen-induced tumour necrosis
      factor-alpha (TNF-alpha), secreted by previously primed activated macrophages in
      a second-set response. TNF-alpha characteristically injures endothelial cells and
      epidermal keratinocytes. It is thought to induce its cytotoxic effects partly via
      neutrophil degranulation, and partly via DNAase activation, with resultant DNA
      fragmentation and cell lysis. Corticosteroids have been shown not only to inhibit
      TNF-alpha secretion by activated macrophages, but also to block its cytotoxicity,
      thus accounting for the extremely rapid clinical response to this drug in
      conjunction with adequate and appropriate antibiotic therapy.

PMID- 8305321
TI  - Cyclosporin A in the treatment of chronic dermatitis of the hands.
AB  - The efficacy of cyclosporin A (CyA) treatment was studied in seven patients with
      chronic dermatitis of the hands. CyA was started at a daily dose of 2.5 mg/kg in
      five patients, and 1.25 mg/kg in two patients. In patients who responded to the
      treatment at 2.5 mg/kg/day, the daily CyA dose was reduced stepwise, to the
      lowest maintenance dose of 1.25 mg/kg. In patients who did not respond, the dose
      was increased, to a maximum of 5 mg/kg/day. The patients were treated for 2-16
      weeks. In six of the seven patients the dermatitis responded to CyA treatment
      within a few weeks. No response was seen with a starting dose of 1.25 mg/kg/day.
      In three of the five patients with a starting dose of 2.5 mg/kg/day, the daily
      CyA dose could be reduced to 1.25-2 mg/kg/day. After stopping CyA treatment, the
      dermatitis recurred during follow-up in three patients, three remained in
      remission, and one patient was not available for study. Treatment-related side
      effects occurred in three patients. CyA treatment had to be stopped in one
      patient due to headache. The present study suggests that CyA could be a useful
      treatment for chronic dermatitis of the hands not responding to conventional
      therapy.

PMID- 8305322
TI  - Calcipotriol improves the response of psoriasis to PUVA.
AB  - Combining PUVA with other therapeutic agents which reduce the UVA dose required
      for clearance of psoriasis may be of benefit by reducing the long-term risk of
      cutaneous malignancy and by increasing the efficacy of treatment. We have
      therefore studied the effect of calcipotriol in 13 patients with plaque-type
      psoriasis who were about to start twice weekly PUVA. In each patient, from the
      start of PUVA treatment, two plaques on symmetrical body sites were selected for
      assessment. Calcipotriol ointment was applied to one twice daily, and placebo to
      the other. Response was assessed weekly for 6 weeks: an investigator, unaware of
      treatment allocation, compared psoriasis severity within each of the plaques, and
      blood flux was measured using a scanning laser-Doppler velocimeter. Of the 11
      patients who completed the study, in nine the calcipotriol-treated plaque either
      cleared before the placebo-treated plaque (n = 7), or was consistently judged to
      be better (n = 2). From the third week of the trial, mean blood flux was
      significantly lower in the calcipotriol-treated plaques than in those treated
      with placebo. In the seven patients whose psoriasis was clear in at least one
      plaque at the end of the study period, there was a median reduction in UVA dose
      of 26.5% for calcipotriol compared with placebo. With the exception of one
      patient, the improved response was not associated with earlier relapse.

PMID- 8305323
TI  - Short-duration therapy with terbinafine 1% cream in dermatophyte skin infections.
AB  - In a multicentre, double-blind, parallel-group study, the efficacy and safety of
      a single application of terbinafine 1% cream was compared with 3, 5 and 7 days'
      once-daily therapy in the treatment of tinea pedis and tinea corporis/cruris.
      Seventy-eight patients with tinea pedis (58 male, 20 female; mean age 36, range
      19-80) and 21 patients with tinea corporis or tinea cruris (16 male, 5 female;
      mean age 37, range 22-72), presenting in general practice, were entered into the
      study. Of these, 65 patients with tinea pedis and 14 with tinea corporis or
      cruris completed the study and were evaluable. Twenty-eight days after commencing
      therapy 78, 83, 82 and 83% of patients with tinea pedis in the 1-, 3-, 5-, and 7
      day treatment groups, respectively, were mycologically cured, and 61, 78, 71 and
      67%, respectively, were 'effectively treated'. There was no statistically
      significant difference between treatment groups. Similarly high cure rates were
      seen in patients with tinea corporis and tinea cruris. Three months after
      commencing therapy there was little evidence of relapse. The study shows that
      there is a significant potential for short-duration therapy with terbinafine 1%
      cream in tinea infections of the skin, emphasized here by the high cure rates
      obtained following a single application.

PMID- 8305324
TI  - Proton radiotherapy of skin carcinomas.
AB  - At the Proton Medical Research Center, University of Tsukuba, we performed a
      pilot study of proton-beam radiotherapy in 12 patients with the following types
      of carcinoma: Bowen's disease (4), oral verrucous carcinoma (5), and squamous
      cell carcinoma (3). They received total doses of 51-99.2 Gy in fractions of 2
      12.5 Gy. All of the tumours responded well to the treatment. All four lesions of
      Bowen's disease, three of the five oral verrucous carcinomas, and the three
      squamous cell carcinomas completely regressed following irradiation. Two squamous
      cell carcinomas recurred during the follow-up period. One recurrent squamous cell
      carcinoma was successfully treated by a salvage surgical operation, and in the
      other case the patient refused further therapy. In two verrucous carcinomas there
      was 90% regression of tumour volume. No severe radiation-related complication
      occurred. As proton radiotherapy produces good local tumour control without
      significant morbidity to the surrounding normal tissues, it may prove to be a
      useful therapeutic modality for the treatment of skin carcinomas.

PMID- 8305325
TI  - Cutaneous warts in butchers.
AB  - Several studies have indicated a high prevalence of hand warts in meat handlers,
      although the reasons for this are not clear. The high prevalence may be partly
      due to HPV7, a virus found almost exclusively in meat handlers, but the source of
      HPV7 is not known. We have carried out a cross-sectional survey of hand warts in
      male meat workers and controls from other occupational groups, to investigate the
      reasons for the high prevalence of warts, and particularly of HPV7, in butchers.
      We studied 240 abattoir workers, 246 retail and wholesale butchers, 308
      engineering fitters and 292 office workers. Each subject was interviewed using a
      standard questionnaire, and his hands were examined by a dermatologist. Scrapings
      from the warts were tested for HPV1, HPV2 and HPV7 by a polymerase chain reaction
      method. The prevalence of hand warts was 33.3% in the abattoir workers, 34.1% in
      the butchers, 19.5% in the engineers and 14.7% in the office workers. Scrapings
      were taken from 247 of 267 subjects with warts, and HPV DNA was detected in 151
      samples. The most common viruses were HPV2 (94 men) and HPV7 (76 men). The excess
      of warts in meat workers was largely due to HPV7, which was found in only two of
      the office workers, and was not found in any of the engineers. Logistic
      regression analysis showed no association between the prevalence of hand warts
      (or HPV2 and HPV7 specifically) and hand trauma, cold and wet working conditions,
      smoking, atopy, or handling any particular kind of meat. We suggest that some
      constituent of animal flesh predisposes to replication of HPV7 in keratinized
      epithelium.

PMID- 8305326
TI  - Cutaneous necrosis associated with the antiphospholipid syndrome and mycosis
      fungoides.
AB  - The development of extensive cutaneous necrosis in a patient with tumour-stage
      mycosis fungoides is described. Skin biopsies showed a lymphomatous infiltrate,
      and thrombosis of dermal blood vessels. Investigation revealed the presence of
      anticardiolipin antibodies, a lupus anticoagulant, and low free protein S, which
      contributed to a prothrombotic state. Antiphospholipid antibodies have been
      detected in non-Hodgkin's lymphoma, but clinical manifestations are uncommon.
      Such autoantibodies may be produced by neoplastic lymphoid cells. The frequency
      with which antiphospholipid antibodies occur in mycosis fungoides is currently
      unknown.

PMID- 8305327
TI  - Rapp-Hodgkin syndrome and AEC syndrome: are they the same entity?
AB  - Rapp-Hodgkin syndrome and AEC syndrome are two disorders in which ectodermal
      dysplasia and clefting are associated. Rapp-Hodgkin syndrome is an autosomal
      dominant condition characterized by cleft lip and palate, peculiar craniofacial
      features, and ectodermal dysplasia, consisting of abnormalities of teeth, hair,
      nails and sweating. AEC syndrome manifests the same defects plus ankyloblepharon
      and a higher frequency of scalp dermatitis. A child affected by ectodermal
      dysplasia associated with clefting, ankyloblepharon, severe scalp dermatitis, and
      the characteristic Rapp-Hodgkin facies is reported. The overlap between Rapp
      Hodgkin syndrome and AEC syndrome is discussed. Critical review of both disorders
      suggest that AEC syndrome and Rapp-Hodgkin syndrome represent the same entity.

PMID- 8305328
TI  - Flow cytometric enumeration and kinetic analysis of inflammatory cell populations
      in breast carcinomas.
AB  - Inflammatory cell populations were quantitated in 76 consecutive mechanically
      dissociated clinical breast carcinoma specimens using multiparameter, two-color
      (PI-cytokeratin/FITC, PI-LCA/FITC) flow cytometric analysis. The percent LCA
      positive events varied from 1.3-62.5% (mean = 11%) and correlated with degree of
      histologic inflammatory cell infiltrate (mild-5.8% LCA+events vs. marked-35.9%
      LCA + events, P < 0.001), abnormal DNA content (diploid range--4.6% LCA + events
      vs. aneuploid--13.3% LCA + events, P = 0.003) and poor tumor differentiation
      (well-moderate-6.5% LCA+events vs. poor--19.9% LCA + events, P = 0.001).
      Synthesis phase fractions in LCA-positive populations were uniformly less than
      the corresponding cytokeratin (CK)-positive cells (mean LCA + SPF = 4.4% vs. mean
      CK + SPF = 15.5%) and varied from 3-11%. Proliferation among inflammatory
      populations did not correlate statistically with the total percent of LCA or CK
      positive events, nor with the SPF in epithelial populations. However,
      proliferative activity of inflammatory components was greater in tumors with
      predominately intratumoral, vs. peritumoral, inflammatory cell distribution (4.6%
      vs. 3.3%, P = 0.03) and in tumors with greater numbers of large, 'transformed'
      lymphocytes (few = 3.25% vs. many = 6.5% LCA + SPF, P = 0.001). We conclude
      multiparameter flow cytometric analysis of mechanically-dissociated breast tumors
      is representative of tumor infiltrating lymphoid populations in breast tumors and
      provides a potentially useful means of studying biologically relevant tumor-host
      interactions.

PMID- 8305329
TI  - Correlation between DNA ploidy and clinical features in smooth muscle tumors of
      the gastrointestinal tract.
AB  - Paraffin-embedded tissue samples from 51 surgically resected, gastrointestinal
      smooth muscle tumors (10 leiomyomas, 5 leiomyoblastomas and 36 leiomyosarcomas)
      were assayed for nuclear DNA content, and the results were examined for
      correlation with clinico-pathological variables (tumor size, cellularity and
      mitosis) and prognosis. Twenty-four (47%) of the 51 tumors, consisting of 3 (30%)
      of the 10 leiomyomas, 2 (40%) of the 5 leiomyoblastomas and 19 (53%) of the 36
      leiomyosarcomas, were identified as aneuploid. A close correlation was found
      between the mitotic index and the tumor size (<cc> = 0.528; P < 0.001). The DNA
      ploidy pattern of the leiomyosarcoma was closely correlated with the patient
      survival periods (P = 0.06). The estimated median survival period was 73 months
      for patients with diploid tumors, and 51 months for those with aneuploid tumors.
      The 10-year survival rate for aneuploid tumors was lower than that for diploid
      tumors (P < 0.001). The measurement of DNA content may provide an index of
      prognostic value in gastrointestinal leiomyosarcomas.

PMID- 8305330
TI  - Caveats in the estimation of DNA-ploidy in paraffin embedded specimens of primary
      prostate cancer and lymph node metastases by flow and image cytometry.
AB  - DNA ploidy assessments of 72 archival paraffin embedded specimens were made
      utilizing flow cytometry (FCM) and image cytometry (ICM). Forty four specimens
      were obtained from primary prostatic tumours and 28 from metastatic lymph nodes.
      Eighteen of 30 FCM diploid range tumours were aneuploid by ICM. Nineteen of 22
      FCM tetraploid range tumours were ICM aneuploid. All FCM non-diploid range
      specimens were non-diploid range by ICM, and all ICM diploid range specimens were
      diploid range by FCM. ICM more easily identifies small numbers of aneuploid cells
      than FCM. Discrepancy between FCM and ICM measurements was particularly high in
      lymph node specimens. FCM diploid range distributions mostly occurred in lymph
      nodes with a small tumour fraction whereas the number of aneuploidy specimens
      increased with larger tumour volume. Lymphocytes are different from solid tumour
      cells since they are not fixed in tissue and will probably be more easily
      dissolved in cell suspension when sections are disintegrated. This may influence
      FCM measurements and has to be considered when DNA ploidy measurements of lymph
      node metastases are made.

PMID- 8305331
TI  - Morphometric and tridimensional studies of tubular cystic degeneration in rat
      kidney following exposure to cisplatin.
AB  - Cisplatin, a widely used chemotherapeutic agent, is characterized by a dose
      limiting renal toxicity. Cystic tubular dilatation is the most typical
      histopathological alteration encountered in cisplatin-treated rats. The purpose
      of the present study was to explore by a morphometric approach the development of
      cystic degeneration and, in particular, to analyse, by computer-assisted
      tridimensional reconstructions, the spatial structure and the tubular origin of
      cisplatin-induced renal cysts. This study was performed on rats given 8 mg/kg
      cisplatin i.p. for four days and sacrificed 4, 7, 14, 21, 50 and 60 days after
      last drug administration. The relative area occupied by cystic tubules increased
      rapidly in the outer stripe of outer medulla (OSOM) and reached a maximum 21 days
      after the end of treatment. Cystic dilatations appeared later in the kidney
      cortex and the inner stripe of outer medulla (ISOM). The tridimensional study of
      cystic tubules located in OSOM confirmed previous reports indicating that they
      arise from proximal straight tubules and showed that cystic degeneration was not
      associated with atrophy or degeneration in more proximal parts of the nephron.
      Moreover, cystic tubules located in ISOM were found to originate from distal
      straight tubules and/or the loop of Henle, an observation which, to our
      knowledge, has not been reported so far in cisplatin-treated rats.

PMID- 8305332
TI  - Clinical trials in cancer: who should pay?

PMID- 8305333
TI  - Need for a common language?

PMID- 8305334
TI  - The Christie Hospital breast conservation trial: an update at 8 years from
      inception.
AB  - In 1990, we published the results of a clinical trial involving 708 patients with
      breast carcinoma of 4 cm or less in diameter, who, following lumpectomy, were
      randomized to have radiotherapy to the tumour bed only (limited field, LF group)
      or to the whole breast and regional nodes (wide field, WF group). No adjuvant
      systemic therapy was prescribed. At the time the median follow-up was 37 months.
      We present the updated results after an extended median follow-up of 65 months.
      The overall survival is 72.7% and 71.2% for the LF and WF groups respectively.
      The actuarial breast recurrence rate (first event) is 15% (LF) versus 11% (WF)
      for infiltrating ductal carcinoma, whereas, for infiltrating lobular carcinoma,
      the recurrence rate was 34% (LF) versus 8% (WF). A high actual recurrence rate of
      21% (LF) and 14% (WF) was also found for extensive ductal carcinoma in situ. It
      was extremely rare for medullary, mucoid or tubular carcinomas to recur. Salvage
      surgery was possible in 86% (LF) and 90% (WF) respectively. The recurrence rate
      in the breast following lumpectomy and wide field irradiation is comparable with
      others reported in the literature. This trial also shows the lumpectomy with
      limited field irradiation is feasible, albeit with a higher breast recurrence
      rate; the latter could be reduced by improved selection and refinement of the
      technique.

PMID- 8305335
TI  - A pilot study of cisplatin based combination chemotherapy in gastric cancer.
AB  - A pilot study evaluating cisplatin in combination with 5-fluorouracil,
      methotrexate and epirubicin in advanced gastric cancer was initiated. Twenty
      patients were treated, eight with locally advanced or recurrent disease, and 12
      with metastatic gastric cancer. The overall response rate was 35% (95% confidence
      interval 14%-56%).

PMID- 8305336
TI  - Weekly cisplatinum concomitant with radical radiotherapy in the treatment of
      advanced head and neck cancer.
AB  - A total of 36 patients with advanced head and neck cancer were treated with
      radical radiotherapy and weekly concomitant cisplatinum chemotherapy. Rapid
      tumour response of both primary tumours and nodes was notable and an initial
      complete response rate of 75% was obtained. The disease free survival was 64% at
      1 year and 52% at 2 years. The protocol proved feasible with little increase in
      toxicity from the addition of chemotherapy. Considering the advanced stage of the
      tumours treated the initial results are promising and this approach would seem to
      warrant further investigation.

PMID- 8305337
TI  - Impaired salivary gland function after radiotherapy compounded by commonly
      prescribed medications.
AB  - Impaired salivary gland function can be a major cause of late morbidity following
      the treatment of head and neck cancer with radiotherapy. A large number of
      commonly prescribed medications can also reduce salivary gland function. We
      report three patients with already impaired salivary gland function following
      successful radiotherapy in whom additional prescribed medication led to an
      increased reduction in salivary flow, thus further impairing the quality of life
      of these patients. Stopping the medication resulted in subjective and objective
      improvement in salivary gland function.

PMID- 8305339
TI  - The 1993 Crookshank Lecture of the Royal College of Radiologists, given by Sir
      Richard Southwood. Risks from radiation: perception and reality.

PMID- 8305338
TI  - External beam radiotherapy for carcinoma of the prostate: a retrospective study.
AB  - Two hundred and thirty-seven consecutive patients receiving radiotherapy for
      primary prostatic carcinoma have been reviewed. The presenting symptoms included
      acute retention (29%), chronic outflow obstruction (78%) and haematuria (12%).
      The diagnosis was confirmed at trans-urethral resection of the prostate (TURP) in
      95%; all but seven patients had adenocarcinoma. The clinical stage at
      presentation was T0 (3%), T1 (9%), T2 (49%), T3 (21%) and T4 (17%). Two hundred
      and six patients (87%) received primary radiotherapy, 38 (16%) had concurrent
      endocrine therapy. Local relapse alone occurred in 38 patients (16%), distant
      relapse alone occurred in 30 (13%), and both local and distant relapse occurred
      in 30 (13%). Median time to local relapse alone was 25 months, distant relapse
      alone 14 months, and local and distant relapse 22 months. Overall survival was
      related to stage and grade at presentation. No influence of endocrine therapy,
      dose or planning technique was seen, but a significant advantage for those
      patients treated using a planned volume compared with parallel opposed fields was
      observed. Acute radiation toxicity affecting the bladder occurred in 42% and the
      bowel in 45%. Late toxicity affecting the bladder occurred in 7% and the bowel in
      2%.

PMID- 8305340
TI  - Prostate cancer: pelvic nodes revisited--sites, incidence and prospects for
      treatment with radiotherapy.

PMID- 8305341
TI  - A patient's viewpoint on current DCIS trials.

PMID- 8305343
TI  - Lung abscesses mimicking multiple pulmonary metastases.
AB  - Five patients receiving chemotherapy for cancer through Hickman central venous
      catheters had lung lesions detected by plain chest radiography or computed
      tomography. In each case these were initially misdiagnosed as metastases,
      although they ultimately proved to be staphylococcal abscesses. Because of the
      grave implications of an erroneous diagnosis of metastatic malignant disease,
      clinicians are urged to consider abscesses in the differential diagnosis of
      radiological chest abnormalities in such patients.

PMID- 8305342
TI  - Multiagent chemotherapy in the salvage cure of ocular lymphoma relapsing after
      radiotherapy.
AB  - The eye has traditionally been regarded as a sanctuary site for drugs, but recent
      publications have shown evidence of penetration by drugs and subsequent clinical
      response of intraocular lymphomas. In this report, a chemotherapy regimen,
      including high dose methotrexate and cytosine arabinoside, was used to re-induce
      remission in a patient with intraocular lymphoma relapsing locally after prior
      radiotherapy. She remains disease free 18 months later.

PMID- 8305344
TI  - Lymphangiography as a staging tool for cervix cancer: limited value after hip
      arthroplasty.
AB  - Lymphangiography (LAG) is often used in the work-up of cervical carcinoma. A
      patient with a history of bilateral hip arthroplasty, who presented with Stage
      IIIB squamous cell carcinoma of the cervix, was sent for lymphangiography. The
      LAG was deemed suboptimal, most likely because of altered lymphatic drainage
      engendered by the previous orthopaedic procedures. As the American population
      ages and hip arthroplasty becomes more common, the value of LAG in such patients
      will need to be reconsidered.

PMID- 8305345
TI  - Spinal cord compression due to metastatic spread from a primary carcinoid tumour
      of the thymus.
AB  - We reported a patient with spinal cord compression due to the metastatic spread
      of a primary carcinoid tumour of the thymus to bone. Prompt surgical
      decompression with local radiotherapy led to good functional recovery and
      survival at 2 years without further recurrence.

PMID- 8305346
TI  - A patient with regressing atypical histiocytosis running a far from benign
      course.
AB  - We describe a case of regressing atypical histiocytosis (RAH) which showed
      evidence of aggressive local disease and systemic involvement. Both the local
      response of this patient to low dose radiotherapy and the systemic response to
      combination chemotherapy were clinically complete and rapidly achieved.

PMID- 8305347
TI  - What do we know concerning fractionation in radiotherapy?

PMID- 8305348
TI  - Hepatocellular carcinoma treated by intralumenal brachytherapy.

PMID- 8305349
TI  - Why do we have to have all these policy documents?

PMID- 8305350
TI  - Implications of overall time in radiotherapy.

PMID- 8305351
TI  - Is time of the essence?

PMID- 8305352
TI  - The long-term outcome after radical radiotherapy for advanced head and neck
      cancer.
AB  - The patterns of local failure, salvage treatment, metastasis, second primary
      tumour and intercurrent disease are observed in 99 patients with advanced head
      and neck tumours, who were entered into a pilot study of CHART. The patients were
      treated between January 1985 and March 1990 and have a median follow-up of 59
      months. All patients presented with squamous cell carcinoma of one of the major
      sites in the head and neck region, with 85% having T3-4 and/or N3 stage disease.
      Complete regression of locoregional disease was achieved in 89% of patients, but
      this fell to 49% at 5 years, 95% of those relapsing did so in the first 24
      months. Using univariant analysis, N-stage influenced local tumour control, with
      N0 disease having a 5-year local tumour control rate of 62% compared with 33% for
      N+ disease. Local tumour control was not influenced by T-stage due to the
      disproportionate number of patients with T1-2 tumours who had nodal disease.
      Three of the 11 patients with residual disease underwent salvage therapy with
      surgery or further radiation; but failed to obtain local tumour control. Of the
      39 patients judged to have recurrent disease two had no histological evidence of
      tumour when surgery was performed. Of the 21 who had salvage surgery 13
      maintained local tumour control to last follow-up or death. Distant metastases
      occurred in 11 patients, all of whom also showed local failure. Thirteen of the
      99 patients developed second primary tumours; these occurred most frequently
      after treatment for oral cavity tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305353
TI  - The long-term outcome after radical radiotherapy for advanced localized non-small
      cell carcinoma of the lung.
AB  - The incidence of locoregional failure, distant metastases and intercurrent
      disease was observed in 76 patients with advanced localized non-small cell lung
      cancer (NSCLC) entered into a pilot study of CHART. Patients were treated between
      January 1985 and March 1990 and have a median follow-up of 62 months. All
      patients had advanced, apparently localized, NSCLC and 76% were considered to
      show mediastinal involvement. Serial computed tomographic (CT) scans were used to
      assess patients' response to treatment, allowing us to determine the contribution
      of locoregional disease to death. Locoregional control was achieved in 32 (42%)
      of the 76 patients, with the figure falling to 23% at 2 years. Metastatic disease
      was demonstrated in 44 patients and, once detected, the median survival time was
      3.8 months. Overall median survival for the group was 12.8 months, with patients
      attaining locoregional control faring better, with a median survival of 27.9
      months compared with 9.9 months for those who did not achieve locoregional
      control. The life-tables show a 52% survival probability at 1 year for the whole
      group, but those attaining locoregional control showed a 75% survival probability
      compared with 39% for patients failing to achieve complete regression; these
      figures fell to 62% and 6% respectively at 2 years. To date, six patients remain
      alive and without evidence of disease at any site, and death has occurred in 12
      without evidence of locoregional disease. The remaining 58 patients died with
      locoregional disease, with 35 also showing evidence of distant
      metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305354
TI  - Idiopathic thrombocytopenic purpura in Hodgkin's disease: a report of eight
      cases.
AB  - Eight patients with idiopathic thrombocytopenic purpura (ITP) in association with
      Hodgkin's disease (HD) are reported from the British National Lymphoma
      Investigation (BNLI) registry. The patients were heterogeneous for initial stage
      of HD, histology and treatment received. The median time from diagnosis of HD to
      diagnosis of ITP was 23 months (range 3-57). Six of eight were in complete
      remission at diagnosis of ITP, one was in relapse, and one was undergoing first
      line chemotherapy. Of those patients developing ITP in remission, only one
      subsequently relapsed. The ITP responded in six of the eight patients to a single
      course of oral prednisolone. Thus the occurrence of ITP in patients with HD
      appears to be independent of the activity of the lymphoma, and responds to
      therapy as for primary ITP. The development of ITP in remission has no prognostic
      significance.

PMID- 8305355
TI  - A prospective randomized double-blind trial comparing ondansetron versus
      prochlorperazine for the prevention of nausea and vomiting in patients undergoing
      fractionated radiotherapy.
AB  - In a multicentre, international double-blind trial, patients undergoing courses
      of five or more daily radiotherapy treatments to the upper abdomen were
      randomized to receive either oral ondansetron 8 mg t.d.s. or oral
      prochlorperazine 10 mg t.d.s. throughout their radiation course in order to try
      to prevent nausea and vomiting. A total of 192 patients were recruited, 135 of
      whom were included in the efficacy analysis; of these, 70 received ondansetron
      and 65 prochlorperazine. Forty-three (61%) of the patients prescribed ondansetron
      and 23 (35%) of those given prochlorperazine had a complete response, with no
      emetic episodes throughout their treatment course (P = 0.002). There was,
      however, no significant difference between the two groups with respect to the
      incidence and severity of nausea. Seventeen (24%) of the patients on ondansetron
      and 19 (29%) of those given prochlorperazine were treatment failures,
      experiencing more than five emetic episodes on their worst day during the study.
      Both drugs were well tolerated, although constipation was seen more commonly with
      ondansetron.

PMID- 8305356
TI  - Short duration radiotherapy in stage I seminoma of the testis: preliminary
      results of a prospective study.
AB  - Ninety-four patients with Stage I seminoma of the testis, treated between
      November 1989 and December 1991, received short duration radiotherapy (2000 cGy
      in 8 fractions) to the para-aortic area only. The treatment was well tolerated
      and, after a median follow-up time of 34 months (minimum 15 months), no patient
      has relapsed in the abdomen. One patient developed an apparently solitary distant
      metastasis from a latent teratoma and is disease free after chemotherapy. This
      form of radiotherapy would appear to be well-tolerated with a low relapse rate.
      It offers the advantage of a simpler and shorter technique compared with
      conventional therapy and avoids the necessity of intensive surveillance to detect
      relapse.

PMID- 8305357
TI  - Liposomal daunorubicin in advanced Kaposi's sarcoma: a phase II study.
AB  - We report a non-randomized Phase II clinical trial to assess the efficacy and
      safety of liposomal daunorubicin (DaunoXome) in the treatment of AIDS related
      Kaposi's sarcoma. Eleven homosexual men with advanced Kaposi's sarcoma were
      entered in the trial. Changes in size, colour and associated oedema of selected
      'target' lesions were measured. Clinical, biochemical and haematological
      toxicities were assessed. Ten subjects were evaluated. A partial response was
      achieved in four, of whom two subsequently relapsed. Stabilization of Kaposi's
      sarcoma occurred in the remaining six, maintained until the end of the trial
      period in four. The drug was generally well tolerated, with few mild symptoms of
      toxicity. The main problem encountered was haematological toxicity, with three
      subjects experiencing severe neutropenia (neutrophil count < 0.5 x 10(9)/l).
      There was no evidence of cardiotoxicity. In this small patient sample, liposomal
      daunorubicin was an effective and well tolerated agent in the treatment of
      Kaposi's sarcoma.

PMID- 8305358
TI  - Liposomal doxorubicin for treatment of AIDS-related Kaposi's sarcoma.
AB  - Sixteen patients with advanced AIDS-related Kaposi's sarcoma received liposomal
      doxorubicin (Doxil, Liposome Technology, Menlo Park, California) at 20 mg/m2
      every 2 or 3 weeks in an open label study, and were evaluated for efficacy and
      toxicity. Eleven patients achieved a partial remission and five had stable
      disease. The median time to achieve a maximum response was two cycles (range 1-3)
      and the median duration of response was 14 weeks (range 6-30). Myelosuppression
      was the commonest adverse event; one patient was withdrawn because of
      neutropenia. Other adverse events were uncommon and mild. Liposomal doxorubicin
      is an effective and safe single agent treatment for advanced AIDs-related
      Kaposi's sarcoma.

PMID- 8305359
TI  - Five case reports of high grade non-Hodgkin's lymphoma in human immunodeficiency
      virus-1 negative homosexual men.
AB  - High grade non-Hodgkin's lymphoma accounts for only 5%-10% of all non-Hodgkin's
      lymphoma. Infection with the human immunodeficiency virus increases the risk of
      developing high grade, usually B-cell, lymphoma, which has been noted to occur
      more commonly in homosexual men. These lymphomas often have unusual clinical
      presentations. We report five cases of high grade non-Hodgkin's lymphoma in HIV
      negative homosexual men who presented to our hospital in a 13-month period. As a
      major centre for the treatment of the acquired immune deficiency syndrome, there
      may be a self-selected homosexual population attending for medical care, and thus
      a bias in the relative incidence of lymphoma seen in this group.

PMID- 8305360
TI  - Double hemibody irradiation (DHBI) in the management of relapsed and primary
      chemoresistant multiple myeloma.
AB  - In view of increasing controversy regarding the role of double hemibody
      irradiation (DHBI) in the treatment of multiple myeloma, we have analysed the use
      of this technique at our institution over a 6-year period. Fifty-five patients
      with multiple myeloma were treated with both upper and lower hemibody irradiation
      between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were
      chemoresistant to initial therapy. Fifteen patients received alpha IFN-2b
      maintenance therapy post-DHBI, at a dose of 3 Mu three times per week, as part of
      a randomized trial. Ninety-five per cent of patients experienced symptomatic
      improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics
      altogether; 63% had a minor biochemical response and 38% had a partial
      biochemical response. The overall survival (OS) and progression free survivals
      (PFS) in all patients were 11 months and 8 months respectively. No significant
      difference was noted in either OS or PFS, according to whether patients were
      chemoresistant or had relapsed post-plateau. alpha IFN did not appear to prolong
      survival (OS or PFS) post-DHBI. Cytopenia was a significant problem, such that
      only 60% of patients had counts adequate enough to be eligible for alpha IFN. We
      conclude that DHBI is an effective treatment in patients with relapsed multiple
      myeloma and in those who are chemoresistant to initial therapy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8305361
TI  - Adjuvant thoracic radiation in small cell lung cancer.

PMID- 8305362
TI  - Cervical cancer, human papillomavirus and vaccines.
AB  - HPV-16 has been strongly implicated in the aetiology of cervical cancer and pre
      malignant cervical intraepithelial neoplasia. Despite current technical
      difficulties it may soon be possible to treat these tumours with anti-HPV-16
      vaccines. A prophylactic vaccine could, in theory, be developed to induce
      neutralizing antibodies to HPV-16 virions in genital secretions, and a
      therapeutic vaccine to elicit cytotoxic T-cell responses against established
      lesions.

PMID- 8305363
TI  - Cartilage: the 'F'-factor fallacy.
AB  - It remains common practice to treat skin lesions overlying cartilage with
      electrons, apparently because of an assumption that radiation absorption
      qualities of non-calcified cartilage are similar to those of bone. We present
      data based on tissue composition and calculated mass absorption coefficients,
      supporting the view that such lesions may safely be treated with superficial X
      rays.

PMID- 8305364
TI  - Acceleration of pubertal development following pituitary radiotherapy for
      Cushing's disease.
AB  - A 7-year-old boy with pituitary dependent Cushing's disease was treated with
      pituitary irradiation following unsuccessful microadenomectomy. This led to
      normalization of the hypercortisolaemia, but was followed by GH deficiency. Two
      years after radiotherapy he had the onset of pubertal development with testicular
      enlargement to 8 ml bilaterally. Pubertal regression was induced using the long
      acting GnRH analogue goserelin. Acceleration of skeletal maturation was also
      arrested, resulting in improvement of final height prediction. Irradiation
      directly to the hypothalamo-pituitary region, as well as whole brain irradiation,
      may thus be associated with accelerated pubertal development.

PMID- 8305365
TI  - Central pontine myelinolysis: report of two occurrences after cisplatin
      containing chemotherapy for nasopharyngeal carcinoma.
AB  - We report two patients with the classical clinical syndrome of central pontine
      myelinolysis following cisplatin based chemotherapy for nasopharyngeal carcinoma.
      The diagnosis was supported by typical features on magnetic resonance imaging.
      Rapid correction of hyponatraemia was the most likely cause. A short course of
      corticosteroids was tried in both patients. Although one patient experienced
      almost complete recovery, the other still suffered from residual motor deficit.
      The importance of careful monitoring of the rate of electrolyte correction is
      emphasized.

PMID- 8305366
TI  - Bone marrow involvement in phenytoin induced 'pseudolymphoma'.
AB  - We report a case of phenytoin induced lymph node enlargement with changes in both
      the lymph nodes and bone marrow suggestive of T-cell non-Hodgkin's lymphoma. The
      condition resolved after phenytoin withdrawal and the patient has no evidence of
      disease on bone marrow biopsy 15 months later.

PMID- 8305367
TI  - Hodgkin's disease: a case of late relapse.
AB  - A case of Stage 1 nodular lymphocytic predominant Hodgkin's Disease relapsing
      after 32 years is described. Recent immunophenotyping suggests that this is a low
      grade B-cell lymphoma.

PMID- 8305368
TI  - Results of endoscopic KTP laser-assisted dacryocystorhinostomy.
AB  - Nineteen consecutive cases of primary endoscopic potassium titanyl phosphate
      (KTP) laser-assisted dacryocystorhinostomy (DCR) were retrospectively studied.
      Follow-up ranged from 10 to 16 months. Patients ranged in age from 18 to 93 years
      (average 65.6 years). Preoperative epiphora was present in all patients, and
      associated with mucopyocele in nine patients. Bicanalicular-nasal silicone tubes
      were placed during surgery in all cases. Timing of tube removal in the office
      ranged from 5 to 15 weeks (average 8.9 weeks). Prolonged patency through the
      follow-up period was achieved in 13 of 19 cases (68.4%). The six cases (31.6%) of
      postoperative failure included three cases with preoperative mucopyocele and
      three cases without. Failures manifested with recurrent epiphora (three cases) or
      recurrent dacryocystitis (three cases); the onset of symptom recurrence varied
      from 7 to 27 weeks postoperatively (average 18.3 weeks). Although success rates
      will vary between surgeons and study populations, patients should be advised that
      the success rate of KTP laser-assisted DCR may be lower than that of standard
      DCR. Generally, indications for choosing laser-assisted DCR include the avoidance
      of a cutaneous incision and reduced potential for mucosal bleeding. The technique
      may be considered for use in selected cases of nasolacrimal obstruction. The
      importance of technical variations remains to be elucidated including rhinostomy
      size and timing of silicone tube removal. Further studies are needed to help
      define the role of endoscopy techniques and lasers in DCR surgery.

PMID- 8305369
TI  - Unilateral ptosis and eye dominance.
AB  - We studied the relationship between eye dominance (Scobee test) and upper lid
      level (MRD) in 54 patients with unilateral ptosis or asymmetric bilateral ptosis
      (> or = 2 mm difference in MRD) using the phenylephrine test. A contralateral lid
      drop was measured in 12/54 patients after instillation of 2.5% phenylephrine in
      the more ptotic eye and occurred in both congenital (3) and acquired (9) ptosis
      cases. A contralateral lid drop was seen in 7/14 (50%) patients whose ptosis was
      greater in the dominant eye and in 5/40 (12.5%) patients whose ptosis was greater
      in the nondominant eye (p = .01). Contralateral lid drops > or = 1 mm were
      present in 7/54 patients, and 6/14 (43%) of them had greater ptosis on the
      dominant side and 1/40 (2.5%) on the non-dominant side (p = .001). There was no
      association between contralateral pseudoretraction and either visual acuity or
      severity of ptosis. These results suggest that levator muscle tone is influenced
      by eye dominance when ptosis is present. The preoperative evaluation of
      unilateral or asymmetrical bilateral ptosis cases should include the Scobee and
      phenylephrine tests to unmask contralateral upper lid pseudoretraction.

PMID- 8305370
TI  - The staged management of ophthalmic complications of facial nerve palsy.
AB  - A six-stage approach to the management of the ophthalmic complications of facial
      palsy was developed to aid the physician in logically organizing therapy and to
      provide patients with reassuring goals. This stepwise approach was applied
      prospectively in 120 consecutive facial palsy patients from 1986 to 1990. The six
      stages included (a) supportive care (with and without tarsorrhaphy), (b) planning
      facial reanimation, (c) lower eyelid and lateral canthal resuspension, (d)
      passive upper eyelid reanimation, (e) dynamic eyelid animation (palpebral
      springs), and (f) soft tissue repositioning including eyebrow lift and
      blepharoplasty. Each stage was considered in order, although action in each stage
      was not appropriate for all patients. All 120 patients received supportive care,
      which was all that was necessary to accomplish the therapeutic goals for 63
      (52.5%). Eight patients received temporary tarsorrhaphies (7%) and 14 (12%)
      permanent. One hundred ten were considered for stage 2. Thirty-five underwent
      stage 3 procedures, 30 received gold weights in stage 4, 5 had palpebral springs
      placed in stage 5, and 6 underwent stage 6 procedures. This staged approach was
      effective in achieving corneal compensation, maintaining vision, and improving
      the quality of life in all patients.

PMID- 8305371
TI  - Variability of mineral density in coralline hydroxyapatite spheres: study by
      quantitative computed tomography.
AB  - Quantitative computed tomography (qCT) can be employed to determine the mineral
      density (MD) of bone or similar mineralized alloplastic materials with high
      precision. Porous spheres made from coralline hydroxyapatite are currently used
      for reconstruction after enucleation procedures. The long-term fate of these
      implants is unknown. Using qCT, MD was determined in hydroxyapatite spheres prior
      to implantation. Intersphere MD varied up to 200% with a near Gaussian
      distribution. Intrasphere MD did not vary significantly when comparing central to
      peripheral sites. The density of coralline hydroxyapatite spheres was
      approximately 400% greater than the density of newly formed endochondral bone.
      This study demonstrates that qCT data were an invaluable tool for MD
      determination, detecting a marked variability in hydroxyapatite MDs. Because the
      long-term fate of these implants is unknown and fibrovascular ingrowth is an
      important event in the integration of these implants, monitoring of MDs of
      coralline hydroxyapatite implants is of interest.

PMID- 8305372
TI  - Repair of the tarsoligamentous sling in New Zealand white rabbits using
      polytetrafluoroethylene graft material.
AB  - Repair of large full-thickness lower lid defects requires reconstruction of the
      tarsoligamentous sling. This may necessitate either a tarsus sharing technique or
      a skin flap with a free cartilage graft. Obtaining tarsus or cartilage in these
      procedures has the disadvantage of requiring a second surgical site, which may
      cause further scarring and deformity. Polytetrafluoroethylene (PTFE) is a
      nonantigenic, inert, highly biocompatible, mechanically strong synthetic material
      that has been successfully utilized as a vascular and soft tissue patch since the
      1970's. PTFE has been used in ophthalmic surgery to wrap orbital implants and as
      an interpositional graft for the correction of lower lid retraction. We evaluated
      the usefulness of PTFE in the reconstruction of the tarsoligamentous sling in 24
      lids of 12 New Zealand white rabbits. PTFE with internodal spacings of 10 and 30
      microns were used initially. Despite a lack of tissue inflammation, the PTFE
      grafts were uniformly extruded by 2 weeks postoperatively. Four additional lids
      were reconstructed using PTFE (30 and 60 microns) coated with a biological
      substrate. This graft material was also extruded. These results suggest that PTFE
      material may not be satisfactory for reconstruction of the tarsoligamentous
      sling.

PMID- 8305373
TI  - Treatment of localized trichiasis with radiosurgery.
AB  - Several treatments exist for trichiasis, a condition in which misdirected lashes
      come in contact with the globe. The treatments can be considered in two groups,
      those that destroy the lash follicle and those that redirect the lashes. No
      technique is without potential complications, and none is 100% effective. The
      Ellman Surgitron FFPF offers a new treatment for trichiasis directed at
      destroying the lash follicle. This instrument utilizes energy at 3.8 MHz in the
      radiofrequency band of the electromagnetic spectrum, hence the term radiosurgery.
      This report presents a prospective, non-masked study of 30 eyelids in 26 patients
      with localized trichiasis treated with the Ellman Surgitron FFPF. Single
      treatment success rate in patient cure was 67%. Complications included lash
      recurrence in 8 patients, eyelid notching in 2, granuloma formation in 1, and
      persistent erythema and tenderness for 1 month in 1 patient. This series
      demonstrates that the instrument can be effectively used to treat localized
      trichiasis. A review of the literature reveals that this technique offers
      potential advantages over some others in use. Further study must determine its
      efficacy in the treatment of diffuse trichiasis and distichiasis.

PMID- 8305374
TI  - Buccal mucous membrane-fat graft in the management of the contracted socket.
AB  - A new surgical technique for reconstructing severely contracted sockets using an
      autogenous buccal mucous membrane-fat graft is presented. The buccal mucosa
      provides replacement of deficient conjunctival surface area; the fat in the
      underlying substantia propria of the buccal mucosa replenishes moderate volume
      deficiency in a single procedure. A custom-designed conformer is used in the
      immediate postoperative period to maintain reconstructed vertical fornices. We
      present four consecutive patients with contracted sockets having both a volume
      deficit and severe conjunctival contracture who were successfully rehabilitated
      using this technique.

PMID- 8305375
TI  - Adnexal findings in AIDS.
AB  - We reviewed the adnexal and orbital findings in a large population with HIV
      infection followed in one medical center. Around 6% of the series had positive
      periocular findings. In 1% of the series, the periocular findings were the first
      manifestation of HIV infection or AIDS. We present the first case of basal cell
      carcinoma in an HIV-infected individual; the carcinoma involved the eyelid.
      Orbital findings included lymphoma, cellulitis, Kaposi's sarcoma, and nonspecific
      inflammatory disease. Adnexal findings included Kaposi's sarcoma, molluscum
      contagiosum, bacterial folliculitis, madarosis, psoriasis, basal cell carcinoma,
      and chalazion. Additional opportunistic infections and tumors involving the
      periocular region are expected to be reported in the future.

PMID- 8305376
TI  - Eccrine adenocarcinoma of the eyelid in a young patient.
AB  - Malignant eccrine adenocarcinoma of the lower eyelids is described in a 16-year
      old girl. This rare tumor has previously been reported only in males, whose
      average age was 64 years. Our patient remains tumor free 7 years after wide
      resection of the eyelid and reconstruction.

PMID- 8305377
TI  - Myositis ossificans masquerading as a recurrent spindle cell lipoma of the orbit.
AB  - A spindle cell lipoma developed in the right orbit of a 43-year-old woman whose
      medical history was only significant for chronic asthma. Sixteen months after
      nearly complete excision of the tumor, the patient presented with eyelid
      swelling, orbital pain, and a calcified apical mass as demonstrated by
      computerized tomography (CT). Recurrent tumor or a second neoplasm was suspected.
      Histologic examination revealed myositis ossificans. To our knowledge, this is
      the first reported case of myositis ossificans in the orbit.

PMID- 8305378
TI  - Pneumomediastinum following blowout fracture of the medial orbital wall: a case
      report.
AB  - An unusual case of cervical emphysema and pneumomediastinum following a blowout
      fracture of the medial orbital wall is presented. Severe pulmonary distress did
      not occur, and the trapped air rapidly absorbed. The source of the emphysema and
      its progression is discussed considering the anatomic relations of the facial and
      cervical subcutaneous space and the mediastinum. To our knowledge, this
      complication is rare and has been documented only once before in an isolated
      blowout fracture of the orbit.

PMID- 8305379
TI  - Massive orbital cyst of the lateral rectus muscle after retinal detachment
      surgery.
AB  - A 73-year-old white man presented with painless proptosis of the right eye 18
      years after retinal detachment surgery on the same eye. Computed tomography (CT)
      showed a mass in the area of the lateral rectus muscle and magnetic resonance
      imaging (MRI) defined the multiloculated cystic mass to be located within the
      lateral rectus muscle. At the time of surgery, a large, thin-walled cystic lesion
      was found within the lateral rectus muscle. Histopathologically, the cystic mass
      was of nonkeratinizing stratified squamous conjunctival epithelium. Massive
      orbital cysts after retinal detachment surgery are rare. The authors review the
      literature and comment on the differential diagnosis and presumed pathogenesis of
      this lesion.

PMID- 8305380
TI  - Pyogenic granuloma after transconjunctival blepharoplasty: a case report.
AB  - This is the first known report of a relatively large postoperative pyogenic
      granuloma developing after a nonsutured transconjunctival blepharoplasty.
      Inflammation and separation or malapposition of the conjunctival wound edges
      probably permitted the lesion to proliferate in the inferior fornix. No foreign
      material could be implicated because no suture was used to close this incision.
      Additionally, Polydek suture material (braided polyester fiber) was associated
      with the complication of a suture tract and granuloma when used for a tarsal
      suspension procedure for ectropion repair in this patient.

PMID- 8305381
TI  - Prevention of lateral migration of silicone tubes in dacryocystorhinostomy:
      selection of suture material.

PMID- 8305382
TI  - The prevalence of lupus anticoagulant and anticardiolipin antibodies in women
      with a history of first trimester miscarriages.
AB  - OBJECTIVE: To determine the prevalence of lupus anticoagulant and raised
      anticardiolipin antibodies in women with a history of two or more miscarriages in
      the first trimester of pregnancy. DESIGN: A prospective study of lupus
      anticoagulant and anticardiolipin antibody levels in unselected women with a
      history of two or more first trimester miscarriages. SETTING: The prepregnancy
      clinic and miscarriage antenatal clinic in a tertiary referral centre. SUBJECTS:
      Two hundred and forty-three women, of whom 113 (47%) had a past history of two
      miscarriages, and 130 (53%) had three or more miscarriages. MAIN OUTCOME
      MEASURES: Quantitative detection of lupus anticoagulant and anticardiolipin
      antibodies; number of miscarriages in women in the normal and the abnormal
      groups. RESULTS: Of the 243 women tested, 41 (16.8%) had an abnormality of lupus
      anticoagulant or anticardiolipin antibodies. This was significantly different
      from the normal population as previously reported. Sixteen women (6.6%) were
      positive for lupus anticoagulant, 20 (8.2%) had elevated anticardiolipin
      antibodies, and five (2%) had both abnormalities. The most frequently positive
      test for lupus anticoagulant was the dilute Russel viper venom time, and IgG was
      the most frequently elevated anticardiolipin antibody. Of the women with a
      history of only two miscarriages, 15% had an abnormality of lupus anticoagulant
      or anticardiolipin antibodies, compared with 18.5% of those with a history of
      three or more miscarriages. This did not reach statistical significance. There
      were 117 (48%) primary miscarriers and 126 (52%) secondary miscarriers. Of the
      primary miscarriers, 17% had an abnormality, compared to 18% of the secondary
      miscarriers. CONCLUSIONS: These findings provide further evidence of an
      association between lupus anticoagulant and anticardiolipin antibodies and early
      pregnancy loss. It is not known if these are the cause of miscarriage, markers
      for miscarriage, or if antiphospholipid antibodies develop as a result of a
      noncontinuing pregnancy. Further studies comparing various treatments are
      required before women with these antibodies can be optimally managed.

PMID- 8305383
TI  - Risk of preterm delivery in pregnant women with group B streptococcal urinary
      infections or urinary antibodies to group B streptococcal and E. coli antigens.
AB  - OBJECTIVE: To establish whether there is an association between preterm delivery
      and either group B streptococcal urinary infection or the presence of urinary
      antibodies to group B streptococcal or E. coli antigens. DESIGN: A prospective
      study with urine culture and antibody measurement performed at the first
      antenatal visit and at 28 weeks gestation. SETTING: Ninewells Hospital, Dundee.
      SUBJECTS: Two thousand and forty-three women registering consecutively at an
      antenatal clinic. MAIN OUTCOME MEASURE: Delivery at less than 37 weeks gestation.
      RESULTS: No increase in preterm delivery was observed in women with positive
      urine cultures for group B streptococci either at booking or at 28 weeks, even
      when confirmed by positive repeat cultures. Preterm delivery was more common in
      women with elevated urinary antibodies to E. coli antigens at booking (relative
      risk 1.81, 95% CI 1.22-2.68, P = 0.005) and at 28 weeks (relative risk 2.36, 95%
      CI 1.60-3.48, P < 0.0001) and to group B streptococcal antigens at 28 weeks
      (relative risk 2.24, 95% CI 1.46-3.43, P = 0.0003). CONCLUSIONS: These data do
      not support previous reports that positive urine cultures for group B
      streptococci are associated with an increased risk of preterm delivery. Our
      report of an association between elevated levels of urinary antibodies and
      preterm delivery is a new finding consistent with the possibility that a local
      inflammatory response to uro-genital infection may be important in stimulating
      the onset of preterm labour. The results suggest that screening for urinary
      antibodies at 28 weeks gestation might help to identify a group of women at
      increased risk of prematurity.

PMID- 8305385
TI  - The effect of neuromuscular blockade on human fetal heart rate and its variation.
AB  - OBJECTIVE: To determine the effect of neuromuscular blockade on fetal heart rate
      and its variation. DESIGN: Case control study. SETTING: Tertiary referral fetal
      medicine unit in a London teaching hospital. SUBJECTS: Forty women with rhesus
      iso-immunisation requiring an intravascular fetal blood transfusion between 28
      and 34 weeks gestation. INTERVENTION: Intravascular injection of pancuronium to
      the fetus prior to fetal blood transfusion in 20 cases. MAIN OUTCOME MEASURES:
      Comparison between the group receiving pancuronium and the control group with
      regard to differences in perceived fetal activity and computer derived numerical
      indices of fetal heart rate and fetal heart rate variation after fetal blood
      transfusion. RESULTS: After transfusion in the control group, there were fewer
      perceived fetal movements, a small reduction in fetal heart rate but no
      differences in number of fetal heart rate accelerations or measures of fetal
      heart rate variation. In the study group, pancuronium produced no change in fetal
      heart rate despite a virtual abolition of perceived fetal movements and fetal
      heart rate accelerations. Measures of fetal heart rate variation were reduced by
      60%. Comparison of the pre- to post-transfusion changes between the two groups
      showed significant differences for all fetal heart rate indices. CONCLUSION:
      Fetal activity accounts for more than half the measured variation of the human
      fetal heart rate.

PMID- 8305384
TI  - The role of Doppler velocimetry in the management of high risk pregnancies.
AB  - OBJECTIVE: To determine whether knowledge of the result of Doppler velocimetry of
      the umbilical artery is beneficial to the management of a high risk pregnancy.
      DESIGN: Randomised controlled trial. The trial was of the management type,
      designed to assess benefit accruing from additional information supplied by
      Doppler velocimetry. SETTING: Tygerberg Hospital, Cape Town, South Africa. The
      hospital serves a population from the lower socio-economic groups. SUBJECTS:
      Women with pregnancies 28 or more weeks gestation with hypertensive diseases
      and/or suspected small for gestational age fetuses were referred for Doppler
      velocimetry. From this population, three subsets were formed: 1. those with
      fetuses with absent end-diastolic velocities (20 fetuses); 2. those with
      hypertension but with fetuses with end-diastolic velocities (89 fetuses); and 3.
      those with fetuses suspected of being small for gestational age but with end
      diastolic velocities (104 fetuses). INTERVENTIONS: Doppler velocimetry on all
      subjects. The study group consisted of 10 cases with absent end-diastolic
      velocities, 47 cases with hypertensive diseases with end-diastolic velocities and
      51 cases with suspected small for gestational age fetuses but with end-diastolic
      velocities in which the result was revealed to the clinician. The control group
      consisted of 10, 42 and 53 cases, respectively, in which the Doppler results were
      not revealed. All other routine investigations (sonar and antenatal fetal heart
      rate monitoring) were available to the clinicians. Standard management protocols
      were followed in all groups. MAIN OUTCOME MEASURES: Perinatal mortality and
      morbidity, antenatal hospitalisation, maternal intervention, admission to the
      neonatal intensive care unit and hospitalisation until discharge from the
      neonatal wards. RESULTS: In the study and control groups the gestational age at
      entry to the study, maternal age, parity and various complications were not
      significantly different. In the subset with absent end-diastolic velocities,
      there was one neonatal death in the study group, but in the control group there
      were six deaths, five intrauterine and one perinatally related infant death (P =
      0.029). Because of this significant finding, the study was stopped. There were no
      differences in outcome in the subset where there was hypertensive disease with
      end-diastolic velocities between the study and control groups. In the subset in
      which small for gestational age fetuses were suspected, but in which end
      diastolic velocities were present, the women in the study group had significantly
      fewer days in hospital before delivery (P < 0.001) and tended to have fewer
      maternal interventions (study group = 27%, control group = 43%; P = 0.07; odds
      ratio (OR) 0.49, 95% confidence limits (CL) 0.2 and 1.25) and caesarean sections
      (study group = 13%, control group = 27%; P = 0.08; OR 0.43, 95% CL 0.14 and
      1.32). The infants of the study group in this subset also spent significantly
      less time in the neonatal wards (P = 0.029).

PMID- 8305386
TI  - Charts of fetal size: 3. Abdominal measurements.
AB  - OBJECTIVE: To construct new size charts for fetal abdominal circumference and
      area. DESIGN: A prospective, cross sectional study. SETTING: The routine
      ultrasound department of a London teaching hospital. SUBJECTS: The fetuses of 663
      women seen in the routine antenatal booking clinic whose ultrasound and menstrual
      dates agreed within 10 days. METHODS: Fetuses were scanned once only for the
      purpose of the study at gestations between 12 and 42 weeks, when up to 20
      dimensions were measured. Separate regression models were fitted to estimate the
      mean and standard deviation as functions of gestational age. Centiles were
      derived by combining these two regression models, assuming that the measurements
      have a Normal distribution at each gestation. RESULTS: A total of 610 fetuses had
      their abdominal circumference measured directly. Abdominal diameters were
      recorded for 425 fetuses and the circumference was also derived from these, as
      was the abdominal area. New charts for abdominal circumference (directly measured
      and derived from diameters) are presented. The directly measured circumferences
      were consistently (by about 3.5%) greater than those derived from measurement of
      the abdominal diameters. The new charts are compared with previously published
      charts that are in wide use. A chart for abdominal area is also presented.
      CONCLUSIONS: We have constructed new size charts for the fetal abdominal
      circumference, both measured directly and derived from abdominal diameters. We
      have demonstrated the difference between the size charts constructed from these
      two sets of values and hence the importance of using the appropriately derived
      chart when assessing the abdominal circumference. The differences between the new
      charts and previous ones may be largely due to methodological differences.

PMID- 8305387
TI  - Charts of fetal size: 4. Femur length.
AB  - OBJECTIVE: To construct a new size chart for fetal femur length. DESIGN: A
      prospective, cross sectional study of fetuses scanned once only for the purpose
      of the study at gestations between 12 and 42 weeks. SETTING: The routine
      ultrasound department of a London teaching hospital. SUBJECTS: The fetuses of 663
      women seen in the routine antenatal booking clinic whose ultrasound and menstrual
      dates agreed within 10 days. RESULTS: Femur length was measured on 649 of the 663
      fetuses. A linear-cubic regression model was fitted to estimate the mean and a
      separate linear regression to estimate the standard deviation. Centiles were
      derived by combining these two regression models, assuming that the measurements
      have a normal distribution at each gestational age. A new chart for femur size is
      presented and compared with previously published data. CONCLUSIONS: We have
      constructed a new size chart for fetal femur length taking into consideration the
      increasing variability with increasing gestational age. We have compared our
      chart with other published data, and believe that the differences seen may be
      largely due to methodological differences.

PMID- 8305388
TI  - Perinatal findings in children born to HIV-infected mothers. The European
      Collaborative Study.
AB  - OBJECTIVE: To explore in children born to HIV-infected women, the association
      between a child's HIV infection status and birthweight, gestational age,
      congenital abnormalities and other perinatal findings. DESIGN: A prospective
      study of children born to women known to be HIV-infected at or before the time of
      delivery enrolled in the European Collaborative Study. SETTING: Nineteen European
      centres. SUBJECTS: A cohort of 853 children with known HIV infection status.
      RESULTS: There was no evidence for an HIV dysmorphic syndrome, and the frequency
      of congenital abnormalities was similar in infected and uninfected children with
      no consistent pattern of defects. Injecting drug use during pregnancy had the
      most marked effect on birthweight and gestational age. Multivariate analysis
      demonstrated a weak association between birthweight and the child's HIV infection
      status, but this could partly be explained by the confounding effect of maternal
      immunological HIV status. HIV infection in the infant was not associated with
      gestational age, and the mean and distribution of gestational age were similar
      for infected and noninfected children. CONCLUSIONS: The finding that HIV-infected
      and noninfected children are of similar birthweight, the absence of a dysmorphic
      syndrome and no evidence of associated congenital abnormalities suggest that a
      substantial proportion of infection occurs late in pregnancy or at the time of
      delivery.

PMID- 8305389
TI  - Intervention debulking surgery in advanced epithelial ovarian cancer.
AB  - OBJECTIVE: To study whether intervention debulking surgery improves survival in
      patients with advanced ovarian cancer who have bulky (> 2 cm) residual disease
      after primary surgery. DESIGN: A prospective multicentre randomised study.
      SETTING: Hospitals in the West Midlands. SUBJECTS: Ovarian cancer patients with
      bulky residual disease after primary surgery who are considered well enough to
      receive cis-platinum based chemotherapy and further surgery. METHODS: Eligible
      patients were randomised to receive combination chemotherapy alone or combined
      with intervention debulking surgery. MAIN OUTCOME MEASURE: Survival was assessed
      using product limit method and log-rank test. RESULTS: Seventy-nine patients were
      entered into the study. Thirty-seven patients were randomised to intervention
      debulking surgery, 25 (67%) of whom underwent intervention debulking surgery,
      which was performed a median of 13 weeks after primary surgery. The median
      survival for the intervention debulking surgery group was 15 months (95% CI 10-20
      mo) and that of those randomised to chemotherapy alone, which was 12 months (95%
      CI 8-16 mo), were not significantly different (hazard ratio = 0.71; 95% CI 0.44
      1.13). CONCLUSION: Intervention debulking surgery may not improve survival in
      patients with advanced ovarian cancer.

PMID- 8305391
TI  - Labour following caesarean section: current practice in the United Kingdom.

PMID- 8305390
TI  - Bowel dysfunction: a pathogenic factor in uterovaginal prolapse and urinary
      stress incontinence.
AB  - OBJECTIVE: To investigate the aetiological importance of bowel dysfunction in
      patients with uterovaginal prolapse and urinary stress incontinence. DESIGN:
      Observational study using a questionnaire about obstetric history and bowel
      function, and anorectal physiological studies. SETTING: Physiology unit and
      gynaecological outpatients departments of two teaching hospitals. SUBJECTS:
      Twenty-three women with uterovaginal prolapse (mean age 57 years), 23 women with
      urinary stress incontinence (mean age 52 years) and 27 control women (mean age 52
      years). RESULTS: There was no statistically significant difference between the
      three groups in their parity, age or birthweight of their children. However,
      straining at stool as a young adult prior to the development of urogynaecological
      symptoms was significantly more common in women with uterovaginal prolapse (61%
      vs 4%, P < 0.001) and women with urinary stress incontinence (30% vs 4%, P <
      0.05), compared with controls. A bowel frequency of less than twice per week as a
      young adult was also more common in women with uterovaginal prolapse than in
      control women (48% vs 8%, P < 0.001). At the time of consultation, 95% of the
      women with uterovaginal prolapse were constipated, compared with only 11% of
      control women. Many of these women also needed to digitate to achieve rectal
      evacuation. Compared with controls, women with uterovaginal prolapse had a
      prolonged pudendal nerve terminal motor latency (1.9 ms vs 2.2 ms, respectively,
      P = 0.003). Women with stress incontinence of urine had a normal pudendal nerve
      latency (2.0 ms). Other tests of anorectal function were normal. CONCLUSIONS:
      Constipation, in addition to obstetric history, appears to be an important factor
      in the pathogenesis of uterovaginal prolapse.

PMID- 8305392
TI  - Rates of pregnancy outcomes in France.

PMID- 8305393
TI  - Endometrial hyperplasia and adenocarcinoma during tibolone (Livial) therapy.

PMID- 8305394
TI  - Primary pulmonary hypertension and pre-eclampsia: a successful pregnancy.

PMID- 8305395
TI  - Fulminant ulcerative colitis and parturition: a need to alter current management?

PMID- 8305396
TI  - Chronic faecal impaction impairing vaginal delivery at term and first trimester
      termination of pregnancy.

PMID- 8305397
TI  - Advanced in the treatment of the menopause and osteoporosis.

PMID- 8305398
TI  - Memory loss during pregnancy.

PMID- 8305399
TI  - Clinical birthweight standards for a total population in the 1980's.

PMID- 8305400
TI  - Cervical contractions: the response of the cervix to oxytocic stimulation in the
      latent phase of labour.

PMID- 8305401
TI  - Ectopic pregnancy: are biochemical tests at all helpful?

PMID- 8305402
TI  - The thyroid and pregnancy.

PMID- 8305403
TI  - Flexibility in training.

PMID- 8305404
TI  - Female genital mutilation (female circumcision)

PMID- 8305405
TI  - The case against ovarian biopsy for the diagnosis of premature menopause.

PMID- 8305406
TI  - Induction of labour confers benefits in prolonged pregnancy.

PMID- 8305407
TI  - George Lyman Duff Memorial Lecture. Arterial imaging and atherosclerosis
      reversal.
AB  - This review explores evidence for the reversibility of atherosclerosis and
      augmentation of angiography with non-invasive arterial wall imaging. Meta
      analysis from coronary angiographic trials demonstrates that regression and
      stabilization are 1.5 to 2 times more common in treated than placebo subjects,
      and progression is reduced by half in treated subjects. Odds ratios for clinical
      coronary events are significantly reduced with treatment. Lesion improvement
      occurs more readily in women than men and more so in women receiving concomitant
      estrogen replacement therapy. Lesions with > or = 50% diameter stenosis (%S) at
      baseline respond more readily to lipid lowering than those < 50% S, whereas
      reduction in coronary events is related to stabilization of lesions < 50% S.
      Lipoproteins have a differential effect on lesion progression according to lesion
      size, and triglyceride-rich lipoproteins play an important role in the
      progression of coronary artery lesions < 50% S. Improved therapeutic regimens to
      alter progression of atherosclerosis may require adjunctive therapy, such as with
      antioxidants or hormone replacement therapy, in concert with low-density
      lipoprotein cholesterol reduction to prevent new lesion formation or early lesion
      progression. Sequential coronary angiographic determination of progression
      evaluated by both quantitative coronary angiography and global change score, a
      visual assessment of overall lesion change, predicts clinical coronary events.
      Only inferences about the state of the arterial wall can be made from
      angiography, because it delineates only the lumen. Therapy testing and study of
      atherosclerosis progression can be improved with noninvasive B-mode
      ultrasonographic imaging of the distal common carotid artery far-wall intima
      media thickness (IMT), a reliable measure of early preintrusive atherosclerosis.
      Measurement of common carotid IMT is useful for the study of coronary artery risk
      factors and can augment studies of coronary artery intrusive lesions, because it
      is associated with coronary artery disease. B-mode measurement of common carotid
      IMT has the potential of serving as a noninvasive surrogate end point for
      clinical coronary events. Screening for peripheral vessel changes indicative of
      high risk for coronary artery disease is possible and cost-effective with the
      noninvasive procedures now available.

PMID- 8305408
TI  - Factor VII coagulant activity and antigen levels in healthy men are determined by
      interaction between factor VII genotype and plasma triglyceride concentration.
AB  - Ischemic heart disease is caused by a combination of and interaction between a
      number of genetic and environmental factors. In a study of a group of healthy men
      from the United Kingdom, such an interaction was identified between the levels of
      plasma triglycerides and genetic variation determining plasma levels of factor
      VII, a clotting factor that is associated with risk of ischemic heart disease. We
      previously reported a common genetic polymorphism of the factor VII gene that
      changes arginine at residue 353 to a glutamine (Arg353-->Gln) and showed that
      healthy men who carry the allele for Gln353 had lower plasma levels of factor VII
      coagulant activity. This association is strongly confirmed in a new sample.
      Compared with 301 men with the allele for Arg353, 63 men with one or two alleles
      for Gln353 had levels of factor VII coagulant activity that were 20% lower (97.8%
      [95% confidence interval (CI), 95.2% to 100.4%] and 78.2% [CI, 73.8% to 82.9%],
      respectively; P < .0001), with similar genotype-associated differences observed
      for levels of factor VII antigen. The 6 men who were homozygous for the Gln353
      allele had mean levels of factor VII coagulant activity and antigen that were
      lower by 40% and 50%, respectively. In an assay using bovine thromboplastin,
      which is specific for the cleaved (activated) form of factor VII, they had levels
      lower by 60%, suggesting that the major effect of the Gln353 substitution is to
      reduce the proportion of the circulating zymogen that is activated.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8305409
TI  - A new in vitro method for the simultaneous evaluation of cholesteryl ester
      exchange and mass transfer between HDL and apoB-containing lipoprotein
      subspecies. Identification of preferential cholesteryl ester acceptors in human
      plasma.
AB  - To date, several methods have been developed to determine the activity of plasma
      lipid transfer proteins. These methods have largely involved the addition of the
      transfer protein in question to labeled substrates, followed by prolonged
      incubation (4 to 18 hours) and subsequent evaluation of the radioactivity
      transferred to precipitated low-density lipoprotein (LDL). While adequate for
      determining the activity of cholesteryl ester transfer protein (CETP), these
      methods generally do not take into account the composition or levels of
      lipoproteins present within a given individual plasma because pools of high
      density lipoprotein (HDL) are labeled and used for the transfer experiments. Both
      the direction and the extent of lipid transfer are dependent on the composition
      and relative abundance of both donor and acceptor particles as well as the
      activity of the lipid transfer protein(s). Here we describe a new method for the
      determination of the capacity of plasma samples to facilitate cholesteryl ester
      transfer from HDL to LDL and very-low-density lipoprotein (VLDL), a method that
      has several advantages. First, the subject's HDL is labeled and used for
      transfer. Second, the labeled HDL, in a quantity equivalent to 1% of the plasma
      HDL mass, is added to the subject's plasma, and therefore the relative abundance
      of both donor and acceptor particles is preserved at their physiological levels.
      Third, both cholesteryl ester mass and radioactivity are determined, allowing the
      net mass transfer of cholesteryl ester and cholesteryl ester exchange to be
      quantified separately.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305410
TI  - Characteristics of 46 heterozygous carriers and 57 unaffected relatives in five
      Danish families with familial defective apolipoprotein B-100.
AB  - Plasma concentrations of cholesterol, high-density lipoprotein (HDL) cholesterol,
      low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) B, and
      lipoprotein(a) (Lp[a]) in 46 persons heterozygous for the apo B-3500 mutation
      causing familial defective apo B-100 (FDB) were compared with those in 57 non-FDB
      relatives. FDB patients had 50% to 70% higher mean concentrations of cholesterol,
      LDL cholesterol, and apo B than non-FDB relatives (P < 10(-4) for all three
      variables). Triglycerides were higher (P = .016) and HDL cholesterol was lower (P
      = .021) in FDB patients. The concentration ranges of these variables were broad
      in each family, and there was no between-family difference in means for
      cholesterol and LDL cholesterol. There was no phenotype-specific difference in
      Lp(a) concentrations between FDB patients and non-FDB relatives. Apo E4 is
      normally associated with higher concentrations of LDL and apo E2 with lower
      concentrations. This relation was partly reversed in FDB patients: apo E4 was
      associated with lower apo B concentrations and apo E2 with higher apo B
      concentrations. Tendon xanthomata were found in members of two of the five
      families. Six of 12 FDB patients > 50 years old had atherosclerotic disease. In
      contrast, all 18 non-FDB relatives > 50 years old were apparently healthy. A
      total of 8 FDB patients with atherosclerotic disease had 36% higher cholesterol
      concentrations, 28% higher apo B concentrations, 50% higher triglyceride
      concentrations, and 120% higher Lp(a) concentrations than FDB patients without
      clinical atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305411
TI  - Dietary fat induces changes in factor VII coagulant activity through effects on
      plasma free stearic acid concentration.
AB  - Previous studies have demonstrated activation of the contact system of
      coagulation and an increase in factor VII coagulant activity (VIIc) when citrated
      plasma is incubated in the presence of micellar stearate. The products of contact
      activation, factors XIIa and IXa, were responsible in this system for the
      activation of factor VII, thereby increasing factor VIIc. To obtain evidence that
      these in vitro interactions also operate in vivo, factor VIIc was examined in
      relation to plasma free fatty acid concentrations in five healthy individuals
      during the consumption of isocaloric high-saturated fat, high-unsaturated fat,
      and low-fat diets, each taken for 4 weeks in random order and separated by
      intervals of 12 weeks. For all but the final 3 days of each phase, subjects
      selected appropriate foods from prepared lists to meet the dietary requirements.
      Experimental diets of predetermined fat content and composition were fed on days
      26 through 28 in each phase. Fat supplied on average 62% of energy in two of the
      experimental diets and less than 20% of energy in the third. On the final day of
      each dietary phase, the concentrations of the various free fatty acids and factor
      VIIc were measured before breakfast and at three 150-minute intervals thereafter.
      Plasma factor VIIc was, respectively, 6.5% and 13.1% of standard higher on the
      unsaturated and saturated fat diets than on the low-fat diet. Furthermore, the
      plasma concentration of stearic acid was strongly associated with factor VIIc (r
      = .58; P < .0001), and this relation remained significant (P = .003) after
      allowance for the plasma concentrations of palmitic, oleic, and linoleic
      acids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305412
TI  - Tissue-factor pathway inhibitor and lipoproteins. Evidence for association with
      and regulation by LDL in human plasma.
AB  - Tissue-factor pathway inhibitor (TFPI) is a potent inhibitor of extrinsic
      coagulation, which is mainly associated with lipoproteins in circulating blood.
      Gel filtration of human plasma confirmed the presence of three peaks in which
      approximately 10%, 70%, and 20% of total TFPI activity was retained.
      Precipitation of very-low-density lipoproteins and low-density lipoproteins
      (LDLs) in plasma by polyethylene glycol almost completely abolished peaks and I
      and II. LDL isolated by ultracentrifugation revealed two peaks of TFPI after gel
      filtration that coeluted with peaks I and II, respectively, from gel filtration
      of total plasma. TFPI activity in peaks I and II was also precipitated by anti
      apolipoprotein B antibodies. Fourteen patients with familial hypercholesterolemia
      had higher plasma TFPI activity than did age- and sex-matched normolipemic
      control subjects (1.45 +/- 0.27 U/mL versus 0.80 +/- 0.09 U/mL, P < .001). Plasma
      TFPI was correlated with LDL cholesterol (r = .73, P < .001) and apolipoprotein B
      (r = .69, P < .001). No association was found with high-density lipoprotein
      cholesterol or apolipoprotein A-I. In a double-blind, placebo-controlled trial
      among the familial hypercholesterolemia patients, lovastatin alone or in
      combination with fish oil concentrate lowered plasma TFPI in parallel with LDL
      cholesterol. Gel filtration of plasma from these patients demonstrated a specific
      drop in apolipoprotein B-TFPI complexes, whereas TFPI not associated with
      lipoproteins was unchanged. This study demonstrated that plasma TFPI was
      associated with and regulated by LDL in plasma from healthy subjects and patients
      with familial hypercholesterolemia.

PMID- 8305413
TI  - Mechanical properties of model atherosclerotic lesion lipid pools.
AB  - Structural analysis of atherosclerotic coronary arteries has suggested that
      stress concentrations are associated with plaque rupture and that these stress
      concentrations are critically dependent on the geometry and mechanical properties
      of the fibrous cap and lipid pool. Recent clinical trials of lipid-lowering
      therapy have shown a significant reduction in cardiac events associated with
      plaque rupture perhaps because of the changing composition of subintimal lipid
      pools. To test the hypothesis that changes in lipid composition can change the
      mechanical properties of lipid pools, we measured the dynamic shear moduli of
      combinations of cholesterol monohydrate crystals, phospholipids, and
      triglycerides similar to those found in atherosclerotic lesions. Increasing the
      cholesterol monohydrate concentration from 0% to 50% increased the real component
      of the dynamic shear modulus (storage modulus or stiffness) by 4.5 times at a
      frequency of 1 Hz (P < .001). All specimens demonstrated an increase in stiffness
      with increasing frequencies of stress ranging from 0.1 to 3 Hz. We conclude that
      the stiffness of model atherosclerotic plaque lipid pools is related to the
      concentration of cholesterol monohydrate crystals. Because the relative
      concentration of cholesterol monohydrate increases during early regression of
      experimental atherosclerosis, the resultant stiffening of the lipid pool may
      reduce stresses in plaque caps. However, the magnitude of the contribution of
      changing lipid stiffness to the reduction of cardiac events seen in clinical
      studies is unclear.

PMID- 8305414
TI  - Overexpression of human lipoprotein lipase enhances uptake of lipoproteins
      containing apolipoprotein B-100 in transfected cells.
AB  - To investigate the role in lipoprotein metabolism of lipoprotein lipase (LPL)
      secreted by tissues, we established two cell lines. Fusion plasmids containing
      either human LPL cDNA or antisense LPL cDNA under control of the cytomegalovirus
      promoter were transfected into Chinese hamster ovary (CHO) cells, designated as
      CHO-LPL and CHO-anti-LPL, respectively. CHO-LPL constitutively produced a high
      level of LPL, whereas CHO-anti-LPL produced a minimal level. When very-low
      density lipoprotein (VLDL) was incubated with CHO-LPL, VLDL triglycerides were
      hydrolyzed, intermediate-density lipoprotein (IDL) was produced, and
      apolipoprotein E contents increased. CHO-LPL took up and degraded 125I-VLDL at 37
      degrees C four times more strongly than did CHO-anti-LPL. Whereas the degradation
      of apolipoprotein E-deficient VLDL was only 12% that of normal VLDL in CHO-LPL,
      structural changes of the lipoprotein, including apolipoprotein E expression on
      the lipoprotein surface, may be important for the cellular uptake of VLDL.
      Furthermore, we found that binding at 4 degrees C of VLDL and LDL to CHO-LPL was
      greater than to CHO-anti-LPL, and this binding difference was abolished by
      washing the cells with heparin. This suggests that cell surface LPL plays a role
      in the binding of lipoproteins to the cells. We conclude that both the
      composition of VLDL particles and their cellular binding are influenced by LPL
      secreted by cells, both of which may enhance the cellular uptake of VLDL.

PMID- 8305415
TI  - Aortic permeability to LDL during estrogen therapy. A study in
      normocholesterolemic rabbits.
AB  - 17 beta-Estradiol has recently been found to inhibit atherogenesis by mechanisms
      that are in part independent of the estrogenic action on plasma lipoprotein
      levels. Since aortic permeability to low-density lipoprotein (LDL) in
      normocholesterolemic rabbits is a strong predictor for subsequent atherosclerosis
      during hypercholesterolemia, the present study investigated a possible influence
      of 17 beta-estradiol on aortic permeability to LDL. Twenty rabbits were initially
      ovariectomized and then fed a nonatherogenic diet for 10 weeks. One group of
      rabbits (n = 10) received 4 mg of 17 beta-estradiol orally per day; the other
      group (n = 10) received placebo. Serum concentrations of very-low-density
      lipoprotein cholesterol and triglycerides increased significantly more in the
      placebo group than in the estrogen group (P < .03), whereas there were no
      statistically significant differences between groups in LDL, high-density
      lipoprotein, or total cholesterol. At the end of the experiment, 125I-LDL was
      injected intravenously into each rabbit. Aortas were removed 3 hours later, and
      the aortic permeability to LDL was calculated from the radioactivity in the
      plasma and the aortic intima/inner media. The aortic permeability to LDL was
      virtually identical in the 17 beta-estradiol (31.6 +/- 7.2 nL.cm-2.h-1) and the
      placebo (36.9 +/- 7.9 nL.cm-2.h-1) groups (mean +/- SEM). The aortic cholesterol
      content was also similar in the two groups. These data suggest that the plasma
      lipid-independent antiatherogenic effect of estradiol is not mediated through an
      effect on aortic permeability to LDL but rather is related to the metabolism of
      the lipoproteins after they have entered the arterial wall.

PMID- 8305416
TI  - Modification of LCAT activity and HDL structure. New links between cigarette
      smoke and coronary heart disease risk.
AB  - The mechanism(s) through which smoking influences the progression of
      atherosclerosis is poorly understood. Recent evidence suggests that oxidants
      present in the gas phase of cigarette smoke are involved. We exposed human plasma
      to the filtered gas phase of cigarette smoke to assess its effects on plasma
      components involved in the antiatherogenic reverse cholesterol transport pathway.
      In our model, freshly isolated plasma (24 mL) was exposed to filtered air or gas
      phase cigarette smoke for up to 6 hours at 37 degrees C. Lecithin-cholesterol
      acyltransferase (LCAT) activity was dramatically inhibited by cigarette smoke. A
      single 15-minute exposure to the smoke from an eighth of a cigarette was
      sufficient to reduce LCAT activity by 7%; additional exposures resulted in
      further decreases in activity. At 6 hours, only 22% of control LCAT activity
      remained in plasma exposed to smoke. Compared with control, gas-phase cigarette
      smoke-exposed plasma possessed high-density lipoprotein (HDL) with increased
      (16%) negative charge and with cross-linked apolipoproteins AI and AII. These
      data demonstrate that gas-phase cigarette smoke can inhibit a key enzyme (LCAT)
      and modify an integral lipid transport particle (HDL) that are essential
      components for the normal function of the reverse cholesterol transport pathway.
      Gas-phase cigarette smoke-induced modification of the reverse cholesterol
      transport pathway may provide a new mechanistic link between cigarette smoke and
      coronary heart disease risk.

PMID- 8305417
TI  - Antithrombin III inhibits thrombin-induced proliferation in human arterial smooth
      muscle cells.
AB  - Thrombin has attracted increasing attention as a possible mitogen for vascular
      smooth muscle cells in lesion development both after vascular injury and in
      atherogenesis. In this study, the ability of antithrombin III to inhibit alpha
      thrombin-induced DNA synthesis and cell proliferation in human arterial smooth
      muscle cells was analyzed. We demonstrate a concentration-dependent initiation of
      DNA synthesis and cell proliferation by alpha-thrombin. This effect was abolished
      when complex formation with antithrombin III was allowed before thrombin was
      added to the cell cultures. Addition of alpha-thrombin and antithrombin III
      simultaneously at the beginning of the incubation period also resulted in an
      inhibition of thrombin-induced DNA synthesis, but to a lower degree. The
      inhibitory activity of antithrombin III was enhanced in the presence of heparin,
      which on its own had no inhibitory effect on thrombin-induced DNA synthesis. In
      contrast, the mitogenic activity of alpha-thrombin could be inhibited by heparin
      in the presence of low concentrations of serum. This inhibition was dependent on
      the presence of antithrombin III in serum, since heparin lacked effect if
      antithrombin III was depleted from serum by immunoaffinity chromatography.
      Analysis of the enzymatic activity of thrombin showed that the influence on
      catalytic activity of thrombin corresponded to the mitogenic activity of thrombin
      in the presence of heparin, antithrombin III, and serum. The results suggest that
      the mitogenic activity of thrombin is regulated by antithrombin III. Therefore,
      antithrombin III may serve dual functions by inhibiting thrombin in the
      coagulation cascade and by neutralizing its growth-promoting effects on vascular
      smooth muscle cells.

PMID- 8305418
TI  - Ultrasound-determined intima-media thickness and atherosclerosis. Direct and
      indirect validation.
AB  - To evaluate ultrasonographically determined intima-media thickness as a measure
      of early atherosclerosis, three studies were performed. Ultrasound measurements
      of intima-media thickness in the carotid artery were directly validated by
      comparing the same thickness measured by light microscopy. The values were
      closely correlated (r = .82, P < .001). Intima-media thickness determined by
      light microscopy was consistently smaller than that determined by ultrasound,
      probably due to shrinkage during histological preparation. As an indirect
      validation, mean intima-media thickness was calculated in three large groups of
      patients with no plaque (n = 224), one plaque (n = 105), and one circumferential
      or two or more plaques (n = 54) in the carotid bifurcation. Intima-media
      thickness increased significantly with increasing plaque score, indicating that
      diffuse intima-media thickening is more pronounced with more severe
      atherosclerosis. The intima-media thickness also increased with increasing
      multifactorial cardiovascular risk, reflecting a positive relation between signs
      of early atherosclerosis and the burden of known risk factors for the disease.
      Our studies support earlier findings that have found that ultrasonographically
      determined intima-media thickness is a valid way to study early atherosclerosis.

PMID- 8305419
TI  - Fluorogenic assay of activated factor VII. Plasma factor VIIa levels in relation
      to arterial cardiovascular diseases in Japanese.
AB  - Factor VII (FVII) plays an important role in initiation of the tissue factor
      induced coagulation pathway. An increase in FVII coagulant activity (FVIIc) has
      been proposed as an independent risk factor for coronary artery disease. However,
      it remains uncertain whether high FVIIc levels are due to an increase in the
      activation of FVII or an increase in the concentration of FVII mass. We developed
      a new fluorogenic assay for plasma activated FVII (FVIIa) that used soluble
      tissue factor. The sensitivity of this assay ranged from 0.2 to 1000 ng FVIIa per
      milliliter of plasma. Plasma FVIIa levels were measured in 110 healthy subjects
      and 93 patients with hypertension, diabetes mellitus, and/or cardiovascular
      disease. The mean plasma FVIIa level in healthy Japanese individuals was 2.5
      ng/mL, which was lower than that in Western subjects. Gel filtration analysis
      showed that most of the circulating FVIIa was in a free form, and binding of
      FVIIa to tissue factor in plasma was not detected. Aging increased both the FVIIa
      level and FVII mass, whereas menopause increased mainly the FVII mass. Elderly
      patients with arterial cardiovascular diseases showed increases in plasma FVIIa
      levels and FVIIa to FVII antigen (FVII:Ag) ratios. Among the elderly, arterial
      cardiovascular disease was more common in a high-FVIIa than a low-FVIIa group.
      Plasma FVIIa levels were not correlated with serum levels of total cholesterol or
      triglycerides. The FVIIa level and the FVIIa-to-FVII:Ag ratio were positively
      correlated with fibrinogen level and negatively correlated with body mass index
      and serum albumin level in the elderly. In conclusion, aging, cardiovascular
      disease, and malnutrition increased plasma FVIIa levels. FVIIa levels were not
      correlated with lipid levels or hepatic synthesis, suggesting that FVIIa may be
      an independent risk factor for cardiovascular disease.

PMID- 8305420
TI  - Effects of hormone replacement therapy on lipoprotein(a) and lipids in
      postmenopausal women.
AB  - High concentrations of lipoprotein(a) [Lp(a)], an independent risk factor for
      atherosclerosis, cannot be managed by the usual lipid-lowering agents. It has
      been suggested that Lp(a) levels are related to female sex hormones. Estrogen
      replacement therapy makes the lipid profiles favorable for delaying
      atherosclerosis in postmenopausal women. The effects of the combination therapy
      of estrogen and progesterone on lipids are controversial. This study was designed
      to evaluate the effect of female sex hormones on the concentration of Lp(a) and
      to clarify the influence of progesterone on the effect of estrogen in
      postmenopausal women. Postmenopausal women (n = 184) were divided into four
      groups: control; 0.625 mg conjugated equine estrogen (CEE) plus 10 mg
      medroxyprogesterone acetate (MPA); 0.625 mg CEE plus 5 mg MPA; and 0.625 mg CEE
      only. Medication for 2 months lowered the concentrations of Lp(a) by 20% in all
      treated groups. The decrease was more pronounced in subjects with a relatively
      higher basal Lp(a) concentration. Estrogen replacement therapy raised the
      concentration of high-density lipoprotein cholesterol and decreased low-density
      lipoprotein cholesterol without changing total cholesterol. The combination
      therapy of estrogen and progesterone abolished the effect of estrogen on high
      density lipoprotein cholesterol. Hormone replacement therapy lowered Lp(a) levels
      in postmenopausal women. The effect was prominent in subjects with high basal
      Lp(a) levels. This decrease may be one of the mechanisms of the cardioprotective
      effects of estrogen. The cardioprotective effect of estrogen cannot be applied to
      the combination therapy due to the adverse effect of progesterone on high-density
      lipoprotein cholesterol.

PMID- 8305421
TI  - Rat C-reactive protein causes a charge modification of LDL and stimulates its
      degradation by macrophages.
AB  - We have previously shown the binding of low-density lipoprotein (LDL) to
      immobilized rat C-reactive protein (CRP) and the formation of a fluid-phase
      complex between these two proteins. In this report we used immunoelectrophoresis
      and agarose gel electrophoresis to show increased anodic migration of the LDL
      particle as a result of the modification of LDL by rat CRP. The degradation of
      the modified 125I-LDL by rat peritoneal macrophages was increased more than
      twofold in the presence of rat CRP. The increase in rat CRP-mediated 125I-LDL
      degradation by macrophages was dependent on the concentrations of 125I-LDL and
      rat CRP. This increased 125I-LDL degradation was inhibited by phosphorylcholine.
      In contrast, the degradation of 125I-acetyl-LDL by macrophages was not affected
      by rat CRP, although acetylated LDL inhibited the rat CRP-stimulated degradation
      of 125I-LDL. Increasing concentrations of LDL did not affect the degradation of
      rat 125I-CRP by the macrophages, which suggested that the rat CRP and the
      modified LDL did not enter the cell as a complex. Our results suggested that the
      increased degradation of 125I-LDL was caused by the charge modification of 125I
      LDL by rat CRP, due to a fluid-phase complex formation between 125I-LDL and rat
      CRP, and that the degradation involved the scavenger receptor present on the
      macrophages.

PMID- 8305422
TI  - Lipoproteins are major and primary mitogens and growth promoters for human
      arterial smooth muscle cells and lung fibroblasts in vitro.
AB  - Smooth muscle proliferation leading to excessive intimal thickening is of prime
      importance in atherosclerosis. Human arterial smooth muscle cells (SMCs) and
      human lung fibroblasts are rather insensitive to mitogens under plasma-free
      conditions in vitro. This prompted us to study the distribution and nature of the
      growth-promoting material in human plasma. SMCs were obtained from explants of
      human aortic media. More than 80% of the growth-promoting activity of plasma was
      present in the lipoprotein (LP) fraction. The growth-promoting capacity of the
      different LPs was determined on fractions isolated with density gradient
      ultracentrifugation. Cytotoxic effects appeared if low-density lipoprotein (LDL)
      was not protected from oxidation and were aggravated with platelet-derived growth
      factor (PDGF)-BB. Very-low-density lipoprotein, LDL, and high-density lipoprotein
      (HDL) stimulated DNA replication and cell growth by themselves. The stimulation
      was considerable and equaled that obtained with PDGF-BB only. It was strongly
      increased in the presence of PDGF-BB. The effect on SMCs was not uniform for
      subfractions of HDL. A light portion inhibited growth in the absence but strongly
      stimulated it in the presence of PDGF-BB. For fibroblasts, HDL subfractions had a
      uniform effect, suggesting a cell type-dependent difference. Addition of
      cholesterol or essential fatty acids did not induce a growth response similar to
      that of LPs. This speaks strongly against mere nutritional supplementation as
      responsible for the mitogenic and growth-promoting effect of LPs and suggests
      that the effect may be more specific. Disordered LP metabolism is strongly
      related to atherosclerosis, and certain LPs have a potential role for the
      deposition of lipids. In addition to this, the distinct mitogenic and growth
      stimulating effect of LPs by themselves, as demonstrated in the present report,
      suggests a mechanism by which intimal thickening, which is a prerequisite for
      atherosclerosis, may be induced. The pronounced amplification of this effect with
      PDGF-BB, a substance that also has been implicated in atherogenesis, might
      promote growth leading to the excessive intimal thickening in the atherosclerotic
      plaque.

PMID- 8305423
TI  - Antiproliferative effect of desferrioxamine on vascular smooth muscle cells in
      vitro and in vivo.
AB  - Vascular smooth muscle cell (VSMC) growth is a primary component of accelerated
      and spontaneous atherosclerosis. Previous studies have shown that iron may be
      involved in the control of enzymatic activities that modulate DNA synthesis in
      human cells. In this study the effects of the iron chelator desferrioxamine on in
      vitro and in vivo VSMC proliferation were tested. Rat VSMCs in culture and a
      rabbit model of carotid artery balloon injury were used. Desferrioxamine showed a
      significant inhibitory effect on [3H]thymidine incorporation in cell cultures
      that was antagonized by iron supplementation. Desferrioxamine also provided
      effective preventive myointimal VSMC proliferation as assessed by
      bromodeoxyuridine labeling and morphometric analysis of endoluminal stenosis.
      These experiments suggested that iron may be involved in the control of VSMC
      proliferation and that desferrioxamine may have a role in preventing VSMC growth
      and myointimal proliferative lesions.

PMID- 8305424
TI  - Structural relation between HDL-binding proteins in porcine liver.
AB  - We have found strong evidence for a relation between three high-density
      lipoprotein (HDL)-binding proteins of 90, 110, and 180 kDa in porcine liver that
      were detected by ligand blotting. Because HDL-binding proteins with identical
      molecular masses were detected in human liver, all subsequent experiments were
      performed with porcine liver proteins. An antiserum raised against a highly
      purified preparation of the 90-kDa HDL-binding protein, designated 90-PC, showed
      cross-immunoreactivity with the 110- and 180-kDa HDL-binding proteins. Purified
      protein preparations of the 90-, 110-, and 180-kDa HDL-binding proteins were
      obtained and analyzed by polyacrylamide gel electrophoresis with sodium dodecyl
      sulfate. Under nonreducing conditions these preparations showed protein bands
      with the expected molecular masses. Reduction of these preparations resulted in
      protein bands of 90 kDa. Ligand blotting experiments with 125I-HDL showed protein
      bands of 90, 110, and 180 kDa under nonreducing conditions and a 90-kDa protein
      band in all three preparations under reducing conditions. Immunoblotting
      experiments with 90-PC antiserum resulted in a similar pattern. The three protein
      preparations were then subjected to cyanogen bromide cleavage and the resulting
      peptides separated on gel. Immunoblotting with the 90-PC antibody revealed a
      pattern of protein bands that was remarkably similar in all three protein
      preparations. Immunohistochemical localization studies with the 90-PC antibody
      showed that the HDL-binding proteins were present both at the borders of the
      sinusoids as well as within the hepatocellular plates.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8305425
TI  - Characterization of sites with elevated LDL permeability at intercostal, celiac,
      and iliac branches of the normal rabbit aorta.
AB  - En face autoradiography of the endothelium was used to quantify the distribution,
      area, and permeability of sites with enhanced permeability to 125I-low-density
      lipoprotein (125I-LDL) around the intercostal and celiac arteries and at the
      iliac bifurcation of normal rabbit aortas. The density of such sites was highest
      in the upper thoracic aorta and around the celiac and superior mesenteric
      branches and was lowest in the lower abdominal aorta. Permeable sites occurred
      more frequently distal to the intercostal branch orifices and both lateral and
      distal to the orifice at the celiac branch. At the intercostal branch orifices,
      these sites were larger, with a lower permeability and higher frequency than
      those away from the branch. At the celiac flow divider, sites of elevated
      autoradiographic grain density were more permeable and larger than at other
      locations in the abdominal aorta. Mean regional permeabilities were obtained by
      weighted area averages of low- and high-permeability sites. Mean regional
      permeabilities around the intercostal branches were 1.5 times higher than values
      away from the intercostal branches. Within 0.25 and 1 mm away from the celiac
      flow divider, mean regional permeability was 3.1 and 1.3 times higher,
      respectively, than those away from the flow divider. Few sites of elevated
      permeability were found distal to the aortoiliac bifurcation, and the
      permeabilities at the medial and lateral walls of the iliac arteries were not
      different. Mitotic cells were associated with 13 +/- 8% of all sites with
      elevated permeability to 125I-LDL. The frequency of mitotic endothelial cells was
      not increased at branch sites, suggesting that mechanisms other than cell
      replication were responsible for increased LDL permeability in the rabbit. These
      results suggest that the permeability and frequency of occurrence of sites with
      elevated permeability around the celiac and intercostal branches may influence
      the distribution and severity of early lesions in rabbits fed a
      hypercholesterolemic diet.

PMID- 8305426
TI  - Characterization of an ancestral type of pyruvate ferredoxin oxidoreductase from
      the hyperthermophilic bacterium, Thermotoga maritima.
AB  - The hyperthermophilic bacterium, Thermotoga maritima, is a strict anaerobe that
      grows up to 90 degrees C by carbohydrate fermentation. We report here on its
      pyruvate ferredoxin oxidoreductase (POR), the enzyme that catalyzes the oxidation
      of pyruvate to acetyl-CoA, the terminal oxidation step in the conversion of
      glucose to acetate. T. maritima POR was purified to electrophoretic homogeneity
      under strictly anaerobic conditions. It has a molecular weight of 113,000 and
      comprises four dissimilar subunits with M(r) values of approximately 43,000,
      34,000, 23,000, and 13,000. It contains thiamine pyrophosphate (TPP) and at least
      two ferredoxin-type [4Fe-4S] clusters per molecule, as determined by iron
      analysis and EPR spectroscopy. CoASH was absolutely required for pyruvate
      oxidation activity, while the addition of TPP was stimulatory. The apparent Km
      values at 80 degrees C for pyruvate, CoASH, and TPP were 14.5, 0.34, and 0.043
      mM, respectively, and the corresponding apparent Vm values ranged from 154 to 170
      mumol of pyruvate oxidized/min/mg (units/mg). The apparent Km and Vm values for
      T. maritima ferredoxin, the proposed physiological electron carrier for POR, were
      26 microM and 280 units/mg, respectively. POR did not use 2-oxoglutarate, phenyl
      pyruvate, or indolyl pyruvate as substrates. The enzyme was extremely
      thermostable: the temperature optimum for pyruvate oxidation was above 90 degrees
      C, and the time for a 50% loss of activity (t50%) at 80 degrees C (under
      anaerobic conditions) was 15 h. The enzyme was also very sensitive to
      inactivation by oxygen, with a t50% in air at 25 degrees C of 70 min.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8305427
TI  - Pyruvate ferredoxin oxidoreductases of the hyperthermophilic archaeon, Pyrococcus
      furiosus, and the hyperthermophilic bacterium, Thermotoga maritima, have
      different catalytic mechanisms.
AB  - Pyruvate ferredoxin oxidoreductase (POR) has been previously purified from two
      hyperthermophiles, the archaeon Pyrococcus furiosus (Pf, Topt = 100 degrees C)
      and the bacterium Thermotoga maritima (Tm, Topt = 80 degrees C). Each catalyzes
      the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2 near the optimal
      growth temperature of the organism and are virtually inactive at 25 degrees C.
      Both PORs contain a thiamine pyrophosphate (TPP) cofactor and at least two [4Fe
      4S] ferredoxin-type clusters. We have now shown, using EPR spectroscopy and metal
      analyses, that PfPOR also contains an unusual copper center that is not present
      in Tm POR. In addition, distinct catalytic intermediates were generated in both
      enzymes by the addition, separately and in combination, of the substrates
      pyruvate and CoASH, and these were examined by EPR spectroscopy. The addition of
      pyruvate to oxidized Pf POR produced an isotropic signal centered at g = 2.01,
      which was measurably broader in the presence of pyruvate-2(13)C. This signal,
      which was assigned to a (hydroxyethyl)thiamine pyrophosphate radical
      intermediate, was not observed in Tm POR under the same experimental conditions.
      Incubation of the oxidized enzymes with CoASH resulted in the partial reduction
      of the copper site in Pf POR and the partial reduction of a novel iron-sulfur
      center in Tm POR, which was not seen in the dithionite-reduced enzyme. The
      addition of both pyruvate and CoASH to the PORs in their oxidized states resulted
      in the reduction of the same iron-sulfur centers that are reduced by sodium
      dithionite.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305428
TI  - Microheterogeneity in glycosylphosphatidylinositol anchor structures of bovine
      liver 5'-nucleotidase.
AB  - In our study, 5'-nucleotidase was released from bovine liver by the treatment
      with Bacillus thuringiensis phosphatidylinositol-specific phospholipase C and
      purified to a homogeneous state by concanavalin A-Sepharose and
      (diethylaminoethyl)-Toyopearl column chromatography and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Purified 5'-nucleotidase were then cleaved by
      cyanogen bromide (CNBr), and then inositol phosphoglycan-containing C-terminal
      peptides (IPG peptides) were separated by C18 reverse-phase liquid chromatography
      and analyzed by peptide sequencer, amino acid analyzer, gas chromatography (GC),
      and GC-mass spectrometry (MS). Ser523 of the amino acid sequence deduced from 5'
      nucleotidase cDNA [Suzuki et al. (1993) J. Biochem. (Tokyo) 113, 607-613] is
      revealed to be the C-terminal amino acid to which a glycosylphosphatidylinositol
      is anchored. Separated peaks of CNBr-cleaved IPG peptides were then analyzed by
      electron spray ionization (ESI)-MS. Eight different molecular weight (MW) species
      of CNBr-cleaved IPG peptides were detected. Three fractions of CNBr-cleaved IPG
      peptides were separately treated by trypsin, and trypsinized IPG peptides were
      purified by C18 reverse-phase liquid chromatography. Finally, five different MW
      species of trypsinized IPG peptides (1629.4, 1752.7, 1791.8, 1832.8, and 1994.5)
      were detected by ESI-MS. Together with sequential exoglycosidase treatment and
      quantitative analysis of sugar moieties by GC and GC-MS, microheterogeneity in
      the structures of these five glycosylphosphatidylinositol (GPI) anchor species
      was determined. The common core structure was ethanolamine phosphate-mannose
      mannose-mannose(-ethanolamine phosphate)-glucosamine-myoinositol phosphate.
      Variations observed in additional mannose, N-acetylhexosamine, and ethanolamine
      phosphate moieties form this heterogeneity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305429
TI  - Control of rhodopsin multiple phosphorylation.
AB  - The inactivation of photolyzed rhodopsin requires phosphorylation of the receptor
      at multiple sites near the C-terminus by rhodopsin kinase and binding of a
      regulatory protein, arrestin. In the present study, the phosphorylation sites
      were examined in a partially reconstituted system under several experimental
      conditions. Initial phosphorylation sites were found to be 338Ser, 343Ser, and
      334Ser based on analysis by mass spectrometry of proteolytic peptides from the C
      terminus. The extent of phosphorylation was found to be limited by two
      mechanisms: (1) binding of arrestin to phosphorylated rhodopsin (one to three
      phosphate groups) appeared to prevent further phosphorylation (arrestin has also
      been observed to promote the initial phosphorylation of rhodopsin at 338Ser in
      rod outer segment homogenates); and (2) reduction of the photolyzed chromophore
      all-trans-retinal to all-trans-retinol prevented phosphorylation at more than
      three sites. We propose that previous observations of higher levels of rhodopsin
      phosphorylation may be the result of the removal of endogenous arrestin, or of
      exceeding the capacity of retinol dehydrogenase activity by intense bleaches
      (e.g., by exhausting endogenous NADPH).

PMID- 8305430
TI  - Hydrogen bonding in proteins as studied by amide hydrogen D/H fractionation
      factors: application to staphylococcal nuclease.
AB  - The D/H fractionation factor (sigma) is the extent to which a hydrogen at a
      particular site becomes enriched in 2H over 1H relative to the solvent. A growing
      body of experimental evidence suggest that there is a correlation between the
      value of the fractionation factor and hydrogen-bond strength, with a lower sigma
      value reflecting a stronger hydrogen bond. Fractionation factors of 60% of the
      individual backbone amide hydrogens in the staphylococcal nuclease V8 variant
      (H124L) have been measured for the enzyme in the presence and absence of bound
      ligands (the activating ion Ca2+ and the inhibitor thymidine 3',5'-bisphosphate).
      The method used employed two-dimensional 1H-15N nuclear magnetic resonance
      analysis of uniformly 15N-labeled protein in mixed H2O/D2O solvents.
      Fractionation factors of individual residues were found to range from 0.3 (T120)
      to 1.5 (L38). The sigma value of 0.3 for the NH of T120, which is the lowest
      fractionation factor reported for any system yet studied, suggests that the
      hydrogen bond between T120 HN and D77 O delta 1 is unusually strong. The results
      of previous site-directed mutagenesis experiments [Hinck, A. P. (1993) Ph.D.
      Thesis, University of Wisconsin-Madison, Madison, WI] support the notion that
      formation of this hydrogen bond is important to maintain the stability and
      conformation of the native state. The sigma value averaged over all residues was
      approximately 0.85 for both the unligated and ligated enzymes. Residues in alpha
      helices displayed a slightly lower average sigma value (0.79), whereas residues
      with solvent-exposed amide hydrogens exhibited a slightly higher average figure
      (0.98).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305431
TI  - Proton pumping activity and visible absorption and resonance Raman spectra of a
      cao-type cytochrome c oxidase isolated from the thermophilic bacterium Bacillus
      PS3.
AB  - Cytochrome c oxidase having heme O in addition to heme C and heme A (cytochrome
      cao) [Sone, N., & Fujiwara, Y. (1991) FEBS Lett. 288, 154-158] was isolated from
      a thermophilic bacterium, Bacillus PS3, grown under slightly air-limited
      conditions. Cytochrome cao could oxidize yeast cytochrome c and N,N,N',N'
      tetramethyl-p-phenylenediamine twice as fast as cytochrome caa3, which this
      organism yielded under normal growing conditions. Cytochrome cao also pumped
      protons upon cytochrome c oxidation in a way similar to cytochrome caa3. Binding
      of cyanide to cytochrome cao caused spin-state conversion of heme O at the
      binuclear center and seriously inhibited its physiological activity. A low Ki
      value (0.4 microM) for cyanide was found to be mainly due to a small "off"
      constant. Resonance Raman spectra of cytochrome cao bore close resemblance to
      those of cytochrome caa3 in both oxidized and reduced states, although the formyl
      stretching (vCH=O) band was absent. The Fe-histidine stretching (vFe-His) and Fe
      CO stretching (vFe-CO) frequencies of cytochrome cao were very close to those
      seen for cytochrome caa3, but were distinct from those of hemoglobin and
      peroxidases, suggesting that the protein structure in the vicinity of heme O
      resembles that of the heme a3 moiety of cytochrome caa3.

PMID- 8305432
TI  - Lipoxin biosynthesis by trout macrophages involves the formation of epoxide
      intermediates.
AB  - Rainbow trout macrophages incubated with calcium ionophore A23187 or zymosan
      synthesize a range of lipoxygenase products, including lipoxins from endogenous
      arachidonic and eicosapentaenoic acids. The profile of products formed was
      consistent with the presence of 5- and 12-lipoxygenase activity in intact cells,
      whereas freeze-thaw disruption of macrophages revealed a further 15-lipoxygenase
      activity. To examine the mechanism of lipoxin biosynthesis in these cells,
      macrophages from the hemopoietic head kidney were incubated with potential
      intermediates and substrates, including 5-hydroxyeicosatetraenoic acid (5-HETE),
      5-hydroperoxyeicosatetraenoic acid (5-HPETE), 15-HETE, 15-HPETE, 5,15
      dihydroperoxyeicosatetraenoic acid (5,15-diHPETE), 5,15-dihydroxyeicosatetraenoic
      acid (5,15-diHETE), and LTA4. Only 5-HPETE caused an increase in LXA4 formation,
      while incubation with 15-HETE resulted in the appearance of LXB4, a product not
      formed from endogenous substrates. Alcohol trapping experiments were conducted to
      evaluate the formation of epoxide-containing intermediates during lipoxin
      biosynthesis. Both 12-O-methoxy and 6-O-methoxy derivatives of LTA4/5 were
      formed, together with three groups of tetraene-containing trapping products, one
      of which co-chromatographed with the methanol trapping products generated from a
      synthetic 5(6)-epoxy tetraene. The time course of the appearance of tetraene and
      triene trapping products was similar. Preliminary results are also consistent
      with the presence of epoxide hydrolase activity in trout macrophages that
      converted the 5(6)-epoxy tetraene to LXA4. The results of this series of
      experiments suggest that lipoxin biosynthesis in trout macrophages involves the
      cooperation of 5- and 12-lipoxygenases to yield an epoxy tetraene-containing
      intermediate, or its equivalent, that is specifically converted to LXA4.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8305433
TI  - Extent and rate of proton release by photosynthetic water oxidation in
      thylakoids: electrostatic relaxation versus chemical production.
AB  - The detailed chemical mechanism of the four steps of photosynthetic oxidation of
      two molecules of water to yield molecular oxygen plus four protons is under
      contention. The observed release of protons is a composite of the chemical
      production and more indirect reactions such as electrostatically induced shifts
      of acid/base equilibria of peripheral amino acids. In thylakoids we studied the
      extent and the rate (at microsecond time resolution) of proton release and uptake
      by each of the four oxidation steps. The pattern of net proton release in
      thylakoids varied drastically (between 0.3 and 2 H+/e-) as a function of pH. It
      differed substantially from the pH-dependent patterns of PSII-enriched membrane
      fragments and core particles, but the stepped progression toward release of
      dioxygen (the Kok parameter triple) was about the same. This implied an
      electrostatic origin of this variation and, within the observed limits, a lack of
      (inhibitory) feedback of the uncompensated charge on the electron transfer from
      the catalytic Mn cluster to TyrZ+. The rate of rapid proton transfer to the
      amphiphilic, surface-adsorbed indicator neutral red was proportional to its
      concentration. The shortest half-transfer time was 12 microseconds, substantially
      shorter than the time for electron transfer from Mn to TyrZ+ at any oxidation
      step. Rapid deprotonation thus occurred at the level of TyrZ+. By rapid
      deprotonation acts the four light-driven oxidation steps S0-->S1-->S2-->S3-->S4
      created between 3.4 (at pH 7.4) and 4.5 (pH 6.3) bases per photosystem
      II.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305434
TI  - The dynamics of proton transfer at the C side of the mitochondrial membrane:
      picosecond and microsecond measurements.
AB  - The excited-state proton emitter, pyranine (8-hydroxypyrene-1,3,6-trisulfonate),
      was introduced into the inner aqueous space of inside-out submitochondrial
      particles (SMP). Upon initiation of respiration, the dye recorded acidification
      of this space. Incorporation of high concentrations of the dye (approximately 100
      nmol/mg of protein) had no effect on the respiratory functions of the vesicles,
      nor on their capacity to execute delta microH(+)-coupled reverse electron
      transfer. The respiratory control ratio (RCR) remained as high as RCR > 4. Pulse
      irradiation of the dye caused photodissociation of the proton from the 8-hydroxy
      position. The release of the proton and its reaction with the matrix of the inner
      space of SMP were monitored at two time intervals: nanosecond fluorimetry
      measured the dissociation of the proton from the excited dye molecule (phi OH*),
      while microsecond spectroscopy followed the reaction between the proton and the
      ground-state anion (phi O-). Numerical integration of the differential rate
      equations describes the diffusion of protons in the perturbed system. The
      nanosecond measurements yield the physical characteristics of the aqueous phase
      that dissolves the dye. The apparent dielectric constant of that space is rather
      low (epsilon = 20). The diffusion coefficient of the proton is 2.3 x 10(-5)
      cm2/s, and the activity of water is aH2O = 0.87. All of these values imply that a
      large fraction of the intervesicular aqueous phase is taken up by the hydration
      layer of the lipids and proteins of the C side of the membrane. The microsecond
      dynamics measurements indicate that the rates of proton binding to the membrane
      surface components reach an equilibrium within 60 microseconds.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8305435
TI  - Protein-ubiquinone interaction: synthesis and biological properties of ethoxy
      ubiquinone derivatives.
AB  - For investigation of the protein-ubiquinone interaction in the succinate
      cytochrome c reductase region of the bovine heart mitochondrial electron
      transport chain, ethoxy-substituted ubiquinone derivatives, 2-ethoxy-3-methoxy-
      or 3-ethoxy-2-methoxy-5-methyl-6-decyl-1,4-benzoquinone (EtOQ0C10) and 2,3
      diethoxy-5-methyl-6-decyl-1,4-benzoquinone [(EtO)2Q0C10], were synthesized and
      characterized. These compounds were synthesized from 2,3-dimethoxy-5-methyl-6
      decyl-1,4-benzoquinone (Q0C10) by reaction with sodium ethoxide/ethanol in hexane
      under anaerobic conditions. The products, EtOQ0C10 and (ETO)2Q0C10, were
      separated by thin-layer chromatography using hexane/ether (3.5:1) as the
      developing solvent. The Rf values for diethoxy and monoethoxy derivatives are 0.7
      and 0.6, respectively. The spectral and redox properties of EtOQ0C10 and
      (ETO)2Q0C10 are very similar to those of Q0C10. The reducibility of these
      derivatives by succinate was measured with succinate-Q reductase (SQR), and their
      oxidizability was measured by ubiquinol-cytochrome c reductase (QCR). Ethoxy
      ubiquinone derivatives exhibit concentration-dependent inhibition of SQR
      activity, with (ETO)2Q0C10 being the more potent inhibitor. These derivatives do
      not inhibit QCR and are reduced by succinate-cytochrome c reductase in an
      antimycin-insensitive manner. When used as substrate for QCR, EtOQ0C10H2 has
      about 55%, and (ETO)2Q0C10H2 about 15%, of the activity of Q0C10H2, but with
      lower apparent Km values. The low efficiency of these compounds as electron
      donors is apparently not due to their weak binding to QCR. These results indicate
      that the binding environment of the benzoquinone ring in succinate-Q reductase is
      very specific and differs from that in ubiquinol-cytochrome c reductase.

PMID- 8305436
TI  - Linkages between the dissociation of alpha beta tubulin into subunits and ligand
      binding: the ground state of tubulin is the GDP conformation.
AB  - The effects of ligands on the dissociation of the alpha beta tubulin dimer into
      the two subunits were investigated using calf brain tubulin. Sedimentation
      equilibrium studies showed a number of linkages. In the absence of magnesium in
      the medium, tubulin-GTP, tubulin-GDP, and tubulin with the exchangeable site
      unoccupied associate with essentially the same strength (K alpha beta = 1 x 10(7)
      M-1). This indicates that the ground state of tubulin (i.e., in the absence of
      magnesium) is not affected by occupancy of the exchangeable nucleotide binding
      site (E site). The alpha beta association is enhanced by magnesium ions. The
      association of tubulin with GDP in the E site is linked to the uptake of twice as
      many magnesium ions as that of tubulin with GTP in the E site. This suggests that
      magnesium binding is linked to an E-site-related conformational change.
      Consideration of the linkages between the binding of magnesium ions, E-site
      occupancy, and tubulin conformation in terms of the model [Howard, W. D., &
      Timasheff, S. N. (1986) Biochemistry 25, 8292-8300] in which the tubulin alpha
      beta dimer exists in an equilibrium between two conformations, a microtubule
      forming ("straight") state favored by GTP and a double-ring-forming ("curved")
      state favored by GDP, leads to the conclusion that the ground state of tubulin is
      the ring-forming or "curved" conformation. Thus, in the absence of magnesium, the
      tubulin heterodimer exists in the ring-forming conformation, whether the E site
      is occupied by GTP or GDP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305437
TI  - Effect of colchicine analogues on the dissociation of alpha beta tubulin into
      subunits: the locus of colchicine binding.
AB  - A combination of ligand binding and sedimentation equilibrium studies was used to
      characterize the thermodynamic linkages between alpha beta tubulin association,
      nucleotide binding, and the interaction of colchicine analogues with dimeric and
      dissociated tubulins. The strength of binding of allocolchicine to the tubulin
      dimer was identical (8 x 10(5) M-1) whether the exchangeable nucleotide site (E
      site) was occupied by GTP or GDP. This drug bound to dimeric (alpha beta) tubulin
      and to one of the monomeric subunits, and the binding affinity for the
      dissociated state was linked to occupancy of the exchangeable nucleotide site.
      When the exchangeable site was occupied by GTP, the drug bound with very similar
      affinities to the dimeric and dissociated states of the protein. For tubulin-GDP,
      the binding of the drug to the dissociated state was significantly weaker (6.3 x
      10(4) M-1) than to the dimeric state, suggesting the existence of an E-site
      related conformational change in the dissociated state. Podophyllotoxin, which
      contains the A-ring portion of colchicine, bound with equal affinity to the
      dimeric and dissociated forms of both tubulin-GTP and tubulin-GDP, indicating
      that it is the C-ring portion of colchicine that is linked to the E-site-related
      conformational change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305438
TI  - Phosphorylation-dependent binding of the chemotaxis signal molecule CheY to its
      phosphatase, CheZ.
AB  - Bacterial chemotaxis is accomplished by regulating the direction of flagellar
      rotation. The primary target of the control appears to be CheY, a diffusible
      clockwise-signal molecule which interacts with the switch at the base of the
      flagellar motor and causes clockwise rotation. The regulatory mechanism appears
      to be phosphorylation/dephosphorylation of CheY. Here we demonstrate that CheZ,
      which accelerates the dephosphorylation of CheY, binds to CheY (immobilized on
      CNBr-activated Sepharose beads), that the binding to phosphorylated CheY is
      higher by over 2 orders of magnitude than the binding to nonphosphorylated CheY,
      and that the binding to both the phosphorylated and nonphosphorylated forms of
      CheY is significantly higher in the presence of Mg2+. We also show that the
      mutant proteins CheY13DK, CheY57DE, and CheY109KR bind CheZ to the same extent as
      wild-type CheY. The extent of the binding of these mutant proteins was not,
      however, increased in the presence of acetyl phosphate, the phosphorylating
      agent. The results indicate that neither a conformation which has a clockwise
      causing activity in vivo nor phosphorylation is sufficient, alone, for maximal
      binding of CheZ to CheY and that Mg2+ is required for the binding of these
      proteins as well as for the phosphorylation and dephosphorylation of CheY.

PMID- 8305439
TI  - Properties of isolated recombinant N and C domains of chicken troponin C.
AB  - The two globular N and C domains of chicken troponin C (TnC) are connected by an
      exposed alpha-helix (designated D/E; residues 86-94). Recombinant N (residues 1
      90) and C (residues 88-162) domains containing either F29 or W29 and F105 or W105
      have been engineered and expressed in Escherichia coli. These termination and
      initiation sites were chosen to minimize disruption of side-chain interactions
      between the D/E helix and other residues. W29 and W105 served as useful spectral
      probes for monitoring Ca(2+)-induced structural transitions of the N and C
      domains, respectively [Pearlstone et al. (1992) Biochemistry 31, 6545-6553; Trigo
      Gonzalez et al. (1992) Biochemistry 31, 7009-7015]. By all criteria tested, the
      properties of the isolated F29W/N domain (1-90) were identical to those of the N
      domain in intact F29W. These included fluorescence emission spectra in the
      absence and presence of Ca2+/Mg2+, far-UV CD spectra, and Ca2+ affinity as
      monitored by fluorescence and ellipticity at 221 nm. Similar but not identical
      properties were observed for isolated F105W/C domain (88-162) and intact F105W. A
      summation of the far-UV CD spectra (+/- Ca2+) of the two domains was virtually
      superimposable on that of the intact protein. Of the total Ca(2+)-induced
      ellipticity change at 221 nm, 27% could be assigned to the N domain and 73% to
      the C domain. The data suggest a significant Ca(2+)-induced transition involving
      secondary structural elements of the N domain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305440
TI  - Site selectivity of daunomycin.
AB  - We have reexamined the binding properties of the antitumor drug daunomycin using
      double-helical oligonucleotides 16 base pairs long that were designed to contain
      preferred binding sites for the drug. The preferred sites are contained in a six
      base pair core which is flanked on the 5' and 3' ends by tracts of adenines. The
      flanking sequences, which augment helix stability and reduce and effects, were
      chosen because daunomycin is known to bind poorly to poly(dA).poly(dT). Four
      major sequences were examined in the six base pair core: CGTACG, TAGCTG, TCATCC,
      and (TA)3 and compared with calf thymus DNA. A randomly generated 16 bp sequence
      containing no A tracts and a sequence containing only tracts of As and Ts were
      also used. Fluorometric, absorption, calorimetric, and stopped-flow techniques
      were used to examine the binding. The affinity of the drug for oligomers
      containing known binding sites was comparable to or enhanced relative to that for
      calf thymus bulk DNA. Association constants ranged from 1.0 x 10(8) to 3.0 x
      10(7) M-1. The strongest core binding site found was CGTACG, but its affinity is
      only 2-fold larger than that of other core sequences. Appreciable binding to the
      flanking A tracts was observed. An oligonucleotide which incorporates the CGTACG
      sequence in a short hairpin helix binds an order of magnitude more weakly.
      Complex lifetimes measured by stopped flow generally increase with equilibrium
      stability; the kinetics confirm the existence of a set of weaker sites. The
      exothermic binding enthalpy for daunomycin with the CGTACG core sequence is more
      than twice as large as for the TATATA sequence. Binding to dA20.dT20 is
      endothermic, and a less exothermic component can be detected in the calorimetric
      binding curve of the oligomers containing flanking A tracts.

PMID- 8305441
TI  - Binding affinity and site selectivity of daunomycin analogues.
AB  - We have tested a series of daunomycin analogues for binding affinity to a group
      of oligonucleotides that contain binding sites specific for daunomycin and that
      were previously screened for relative binding affinity for daunomycin. The series
      of drugs differed from daunomycin in the sugar moiety, including substitution of
      a hydroxyl group for the charged amino group and replacement of the 2'-OH by an
      iodo substituent. Data were analyzed by Scatchard plots and association constants
      were estimated from the gamma-intercept at saturating levels of oligonucleotide.
      Because of the solubility problems associated with these compounds, Scatchard
      plots could not be extended to high levels of binding. A second method of
      analysis of the fluorescence data confirmed the semiquantitative association
      constants obtained from the intercepts of the Scatchard plots. The association
      constants were in the range of 10(5)-10(7) M-1. When compared with daunomycin,
      the compounds with hydroxyl substituted for the amino group in the sugar ring
      generally bound less well to the oligonucleotides, by factors of up to several
      hundred. Much of the binding lost upon removal of the charged amino group was
      restored, however, with compounds containing an iodo substituent on the sugar
      ring. Changing the iodo-substituted sugar from the natural L-form to the D-form
      diminished binding by 6-50-fold, depending on sequence. This result implies a
      stereospecific interaction of the natural sugar with the DNA chain. A positively
      cooperative curve was observed in the Scatchard plot for the D-form
      sugar.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305443
TI  - The N-terminal heptapeptide of mitochondrial creatine kinase is important for
      octamerization.
AB  - Mitochondrial creatine kinase (Mi-CK) isoenzymes, in contrast to cytosolic CKs,
      form octameric molecules composed of four stable dimers. Octamers and dimers are
      interconvertible. Removal of the N-terminal pentapeptide of chicken cardiac Mi-CK
      (Mib-CK) by limited proteolysis drastically destabilized the octamer. The role of
      the charged amino acids within the N-terminal heptapeptide was studied in detail
      by progressively substituting the four charged residues by uncharged ones. In
      these altered proteins, the octamer/dimer ratio at equilibrium conditions was
      shifted toward the dimer. Also, the in vitro dissociation rate of octamers into
      dimers was increased in correlation to the number of charged residues eliminated.
      Point mutant E4Q, with only one positive charged amino acid removed, already
      displayed a 50-fold higher equilibrium constant and a 13-fold increased
      dissociation rate compared to wild-type Mib-CK. Mutant 4-7, having all four
      charged residues in the N-terminal heptapeptide substituted, showed a 100-fold
      higher equilibrium constant and a 146-fold increased dissociation rate. The
      corresponding values for double mutant E4Q/K5L were intermediate between the
      single and quadruple mutants. This strongly suggests that the charged amino acids
      in the N-terminal heptapeptide of Mib-CK, and therefore ionic interactions
      mediated by the N-terminal moiety, play an important role in forming and
      stabilizing the octameric molecule. The role of dimer-octamer interconversion in
      vivo as a possible regulator of contact site formation and of mitochondrial
      oxidative phosphorylation is discussed.

PMID- 8305442
TI  - A novel mechanism for coupling of m4 muscarinic acetylcholine receptors to
      calmodulin-sensitive adenylyl cyclases: crossover from G protein-coupled
      inhibition to stimulation.
AB  - Muscarinic m4 acetylcholine receptors are normally coupled through Gi to
      inhibition of adenylyl cyclases. In the olfactory bulb and some cultured cells,
      however, m4 receptors can couple to stimulation of adenylyl cyclase activity. In
      this study, m4 receptors and specific isozymes of adenylyl cyclases were
      coexpressed in HEK-293 cells to characterize the mechanism(s) for m4 receptor
      stimulation of adenylyl cyclases. The calmodulin-sensitive type I and type III
      adenylyl cyclases were chosen for this study because neither enzyme is stimulated
      by the beta/gamma complex of G coupling proteins. M4 receptors exhibited either
      inhibition or stimulation of type I and III adenylyl cyclases depending upon
      receptor density and agonist concentration. Inhibition of adenylyl cyclase was
      apparently due to M4 coupling through Gi. Adenylyl cyclase stimulation through m4
      receptors was not due to increases in intracellular Ca2+ and stimulation of the
      calmodulin-sensitive enzymes since it was evident in isolated membranes in the
      absence of free Ca2+ and with whole cells preloaded with the Ca2+ chelator
      BAPTA/AM. Stimulation of adenylyl cyclase activities by m4 receptors was
      apparently mediated via Gs since it was GTP-dependent, was insensitive to
      pertussis toxin, and was not due to beta/gamma stimulation. Synthetic peptides
      derived from a G protein activating region of the m4 receptor mimicked the m4
      mediated stimulation of adenylyl cyclase activity. These data demonstrate a novel
      mechanism for muscarinic regulation of adenylyl cyclases that may involve
      crossover from inhibitory to stimulatory G protein coupling.

PMID- 8305444
TI  - Membrane properties of antiviral phospholipids containing heteroatoms in the acyl
      chains.
AB  - Phospholipids containing heteroatoms in the lipid acyl chains, e.g., 1,2-bis(12
      methoxydodecanoyl)-sn-3-phosphocholine (L-AC2), exhibit potent anti-HIV activity
      [Pidgeon, C., Markovich, R. J., Liu, M. D., Holzer, T., Novak, R., & Keyer, K.
      (1993) J. Biol. Chem. 268, 7773-7778]. AC2 is a synthetic chemical analog of the
      long-chain phospholipid, dimyristoylphosphatidylcholine (DMPC). Sonicated AC2
      lipid dispersions would not entrap either Dextran-4000 or Mn2+ used as aqueous
      space markers. The lack of entrapment of aqueous space markers indicates that the
      AC2 structures do not contain an aqueous core that is the characteristic
      morphology of conventional lipid vesicles formed by sonication. Transmission
      electron microscopy (TEM) showed that sonicated AC2 lipid dispersions are small
      homogeneous particles approximately 70-100 A in diameter. 1H NMR experiments
      using Mn2+ as a broadening reagent indicated that Mn2+ was accessible to all of
      the AC2 phospholipid headgroups in the AC2 lipid particles formed by sonication.
      The temperature dependence of 1H spin-lattice (T1) relaxation time measurements
      revealed that the motional activation energies increased from the choline
      headgroup to the end of the acyl chains of AC2 molecules in the AC2 lipid
      particles formed by sonication. Collectively these results demonstrate that AC2
      forms micelles. NOESY experiments showed that the AC2 molecules forming the
      micelle structures have hindered motion compared to conventional short-chain
      phosphatidylcholine micelles. 31P NMR spectroscopy and TEM showed that the AC2
      micelles extensively fuse into giant bilayer liposomes (single-layered) when the
      temperature is reduced from above to below the main phase transition temperature
      of AC2. This micelle-to-liposome transition is an irreversible process;
      increasing the temperature above the Tm does not cause the formation of micelles.
      Thus, a main finding is that AC2 micelles formed by sonication are not
      thermodynamically stable because they fuse into large unilamellar vesicles that
      are stable to further changes in temperature. These unusual membrane properties
      of sonicated AC2 dispersions may be important for the antiviral activity and
      metabolism of the phospholipids.

PMID- 8305445
TI  - DNA recognition by alternate strand triple helix formation: affinities of
      oligonucleotides for a site in the human p53 gene.
AB  - Duplex DNA recognition by oligonucleotide-directed triple helix formation is
      generally limited to homopurine target domains. Various approaches have been
      suggested for the relief of this constraint. Artificial DNA sequences have
      previously been used to show that adjacent homopurine domains on opposite DNA
      strands can be simultaneously recognized by oligonucleotide probes that switch
      triple helix recognition motifs between domains. Using assays of electrophoretic
      mobility and chemical protection, we have explored in detail whether such
      strategies are of benefit in designing high-affinity probes for a natural DNA
      sequence in the human p53 gene. This target site contains three adjacent, purine
      rich domains on opposite DNA strands. Our results show that (i) a modest but
      statistically significant enhancement in affinity can be achieved for this
      sequence by designing an oligonucleotide that simultaneously recognizes all three
      purine domains, (ii) correction of a pyrimidine interruption in one purine domain
      does not dramatically alter this result, (iii) the relative energetic and
      structural contributions attributable to recognition of each purine domain can be
      assessed using probes with combinations of specific and nonspecific nucleotide
      sequences, and (iv) probe affinity is not correlated with the apparent number of
      base triplets for certain complexes. These data suggest that unfavorable free
      energy changes may be associated with alternation between triple helix motifs
      using existing strategies. In contrast to artificial DNA sequences optimized for
      this purpose, a substantial affinity enhancement was not observed using alternate
      strand DNA recognition at this natural target sequence. We therefore conclude
      that such enhancement is sequence dependent.

PMID- 8305446
TI  - A photo-cross-linkable tertiary structure motif found in functionally distinct
      RNA molecules is essential for catalytic function of the hairpin ribozyme.
AB  - We have identified an essential UV-sensitive tertiary structure domain within the
      hairpin ribozyme. Irradiation at 254 nm produces two cross-linked RNA species
      that are resolved from the unmodified structure by denaturing gel
      electrophoresis. One cross-link forms at high efficiency and maps between
      nucleotides G21 and/or A22 and U41, all essential bases located within an
      internal loop joining helices 3 and 4. A second cross-link forms between
      nucleotides A20 and U42 as a result of ribozyme dimerization at concentrations
      greater than 0.5 microM. Both cross-linked species retain cleavage activity and
      so presumably reflect catalytically proficient structures of the ribozyme.
      Formation of the intramolecular cross-link is independent of Mg2+ and substrate
      and is blocked by base substitutions within the reactive domain that inhibit
      catalysis. A 36-nt RNA fragment containing the photoreactive domain but lacking
      the substrate binding domain also cross-links with high efficiency and maps
      between G21 and U41, as observed with the intact molecule. The sequence and cross
      linking sites of the UV-sensitive internal loop are strikingly similar to those
      found in several other RNA molecules, including loop E of 5S rRNA. These results
      suggest that the loop E-like structure may be a common RNA folding domain that is
      utilized in a variety of functionally important RNA molecules.

PMID- 8305447
TI  - The light-harvesting chlorophyll a/b-binding proteins.

PMID- 8305448
TI  - Chlorophyll forms and excitation energy transfer pathways in light-harvesting
      chlorophyll a/b-protein complexes isolated from the siphonous green alga,
      Bryopsis maxima.
AB  - In this study, examination was made of chlorophyll (Chl) forms and energy
      transfer pathways in light-harvesting Chl a/b-protein complex (LHC II) isolated
      from the siphonous green alga, Bryopsis maxima. Three major Chl a forms (Ca664,
      Ca672 and Ca679) and one minor form (Ca688) were resolved at 15 degrees C. Two
      Chl b forms were resolved at 648 and 653 nm. Based on the number of Chl bound to
      an apoprotein, two Chls a were assigned to each of the three major Chl a forms,
      and three and five Chls b, to Cb648 and cb653, respectively. At 15 degrees C,
      fluorescence spectra were identical, irrespective of the excitation conditions of
      Chl a, Chl b and siphonaxanthin. Fluorescence from Chl b was detected in addition
      to that from all Chl a forms. Very efficient energy transfer from siphonaxanthin
      or Chl b to Chl a and even uphill transfer from Chl a to Chl b, were noted by
      measurement of the excitation spectra. At 15 degrees C, the equilibrium of energy
      distribution was established among pigments. However, Chl b was found not to
      mediate energy transfer from siphonaxanthin to Chl a. The partial amino acid
      sequence of Bryopsis LHC II was similar to those of green algae and higher
      plants. The energy transfer pathway between pigments and molecular organization
      of Bryopsis LHC II were compared with LHC II isolated from spinach.

PMID- 8305450
TI  - Nucleotide sequences of two hydrogenase-related genes (hypA and hypB) from
      Bradyrhizobium japonicum, one of which (hypB) encodes an extremely histidine-rich
      region and guanine nucleotide-binding domains.
AB  - Sequencing of a 1359-bp (NruI-AccI) DNA fragment located approximately 5.2 kb
      downstream from the end of the hydrogenase structural genes of Bradyrhizobium
      japonicum revealed two open reading frames designated hypA and hypB, encoding
      polypeptides with predicted molecular masses of 12.3 and 32.8 kDa, respectively.
      Both hypA and hypB showed strong homology with other genes in hydrogenase
      containing bacteria. Two 'C-X-X-C' motifs were contained in the deduced amino
      acid sequence of hypA, a motif that is present in all known products homologous
      to HypA. The deduced product of hypB contains an area remarkably rich in
      histidine residues at the N-terminus (24 histidines within a 39 amino acid
      stretch). The deduced HypB also contains GTP-binding domains. We postulate that
      the product of hypB is involved in nickel binding and accumulation, and may
      utilize energy (GTP) to mobilize nickel for its subsequent incorporation into
      hydrogenase.

PMID- 8305449
TI  - Partitioning of electron flux between the respiratory chains of the yeast Candida
      parapsilosis: parallel working of the two chains.
AB  - Partitioning of the electron flux between the classical and the alternative
      respiratory chains of the yeast Candida parapsilosis, was measured as a function
      of the oxidation rate and of the Q-pool redox poise. At low respiration rate,
      electrons from external NADH travelled preferentially through the alternative
      pathway as indicated by the antimycin A-insensitivity of electron flow.
      Inhibition of the alternative pathway by SHAM restored full antimycin A
      sensitivity to the remaining electro flow. The dependence of the respiratory rate
      on the redox poise of the quinone pool was investigated when the electron flux
      was mediated either by the main respiratory chain (growth in the absence of
      antimycin A) or by the second respiratory chain (growth in the presence of
      antimycin A). In the former case, a linear relationship was found between these
      two parameters. In contrast, in the latter case, the relationship between Q-pool
      reduction level and electron flux was non-linear, but it could be resolved into
      two distinct curves. This second quinone is not reducible in the presence of
      antimycin A but only in the presence of high concentrations of myxothiazol or
      cyanide. Since two quinone species exist in C. parapsilosis, UQ9 and Qx
      (C33H54O4), we hypothesized that these two curves could correspond to the
      functioning of the second quinone engaged during the alternative pathway
      activity. Partitioning of electrons between both respiratory chains could occur
      upstream of complex III with the second chain functioning in parallel to the main
      one, and with the additional possibility of merging into the main one at the
      complex IV level.

PMID- 8305451
TI  - Sequence of a mouse embryo cDNA clone encoding proteolipid subunit 9 (P1) of the
      mitochondrial H(+)-ATP synthase.
AB  - A cDNA clone to an abundantly expressed mRNA in cleavage stage mouse embryos has
      been sequenced and identified as encoding subunit 9 (P1) of the mitochondrial
      H(+)-ATP synthase. The deduced amino acid sequence of the mature subunit 9
      protein differs in a single residue from the corresponding rat, ovine, bovine and
      human subunits.

PMID- 8305452
TI  - Lipid unsaturation influences melittin-induced leakage of vesicles.
AB  - Investigation of vesicles composed of different phosphatidylcholines revealed
      that the extent of leakage of internal contents induced by the lytic agent
      melittin can range from practically none to essentially complete, depending upon
      the fatty acyl chain composition of the phospholipid. The extent of leakage
      increases with the number of double bonds in the series
      dioleoylphosphatidylcholine < dilinoleoylphosphatidylcholine <
      dilinolenoylphosphatidylcholine. It depends on the length of the saturated chain
      with 1-myristoyl-2-arachidonoylphosphatidylcholine vesicles being more sensitive
      to melittin induced leakage than 1-palmi-toyl-2-arachidonoylphosphatidylcholine,
      1-stearoyl-2-arachidonoylphosphatidylcholine or 1-palmitoyl-2-
      docosahexaenoylphosphatidylcholine vesicles. The extent of leakage induced by
      melittin from vesicles composed of 1-palmitoyl-2-oleoylphosphatidylcholine,
      dioleoylphosphatidylcholine, 1-palmitoyl-2-arachidonoylphosphatidylcholine and 1
      palmitoyl-2-docosahexaenoyl-phosphatidylcholine increases with the free volume
      parameter of these lipids for 1,6-diphenylhexatriene (Straume, M. and Litman,
      B.J. (1987) Biochemistry 26, 5113-5120). Among the lipid examined here,
      diphytanoylphosphatidylcholine vesicles were least susceptible to melittin
      induced leakage. The results indicate that lipid fatty acyl structure may be
      important in lipid-protein interactions of the kind simulated by melittin.

PMID- 8305453
TI  - Nucleotide sequence of a cDNA for the beta 2 subunit isoform of Na+,K(+)-ATPase
      from human retina.
AB  - Using as probe the entire human liver cDNA clone coding for the beta 2 subunit
      isoform of the Na+,K(+)-ATPase, which lacks the initiation codon ATG, and the
      entire 5'-untranslated region (Martin-Vasallo, P., Dackowski, W., Emanuel, J.R.
      and Levenson, R. (1989) J. Biol. Chem. 264, 4613-4618), we isolated a larger
      clone from a directional human adult retina cDNA library (Swaroop, A. and Xu, J.
      (1993) Cytogenet. Cell Genet. 64, 292-294). This clone, pNH beta 2, shows 100%
      homology with the nucleotide sequence of the human liver cDNA clone and also
      contains additional 407 nucleotides in the 5'-untranslated region, the initiation
      codon and a poly(A) tail. Northern blot hybridization analysis reveals that the
      human mRNA (3.6 kb) is approx. 300 nucleotides larger than the major transcript
      size expressed in rat (3.3 kb). The larger human size mRNA for the human beta 2
      Na+,K(+)-ATPase indicates species differences in gene processing.

PMID- 8305454
TI  - Bioadhesive, collagen-modified liposomes: molecular and cellular level studies on
      the kinetics of drug release and on binding to cell monolayers.
AB  - Liposomes, modified by covalently-anchoring collagen to their surface, were
      investigated for their abilities to be bioadhesive and to act as sustained
      release drug carriers. These bioadhesive liposomes have the potential to induce
      significant improvements in topical and regional therapies. The major findings
      for uni-(ULV) and multilamellar (MLV) bioadhesive liposomes are: (a) Both ULV and
      MLV release small molecular weight drugs over prolonged periods. For example,
      rate constants of (6 +/- 0.5) x 10(-3) and (2.6 +2- 0.8) x 10(-3) h-1, were
      obtained for the release of vinblastine and fluconazole, respectively, from
      collagen-ULV. (b) For a given drug, that rate constant can be shifted (up or
      down) by the choice of liposome type and collagen-surface density and the latter,
      if high enough, lead to the formation of an additional liposome-associated drug
      reservoir. (c) Using monolayers of the A431 cell line to model the in vivo
      targets, the bioadhesive (but not the regular) liposomes were found to bind with
      high affinity to the monolayers. For example, equilibrium dissociation constants
      of 6.3(+/- 3) microM and 2.7(+/- 0.5) microM were determined for bioadhesive MLV
      and ULV, respectively, with corresponding saturation occupancies of 3.7(+/- 1)
      and 4.0(+/- 0.2) pmoles liposomal collagen/monolayer of 10(5) cells. (d)
      Following the retention of bioadhesive MLV at A431 monolayers for 24 h, it was
      found that: at 4 degrees C, 24 h did not suffice to reach equilibrium, but at 37
      degrees C equilibrium binding was obtained within 3-5 h and there was
      quantitative liposome retention (per viable monolayer) thereafter. It is
      concluded that these liposomes are bioadhesive sustained-release carriers, as
      desired, meriting further cellular and in vivo studies.

PMID- 8305455
TI  - The effects of PMA and TFP and alterations in intracellular pH and calcium
      concentration on the membrane associations of phospholipid-binding proteins
      fodrin, protein kinase C and annexin II in cultured MDCK cells.
AB  - Annexin II, alpha-fodrin and protein kinase C (PKC) are associated with the
      cytoplasmic surface of the plasma membranes. When assayed with liposomes, they
      show affinity for acidic phospholipids and bind calcium ions. They also respond
      to or participate in cell signal transduction by altered membrane binding
      properties. In the present work we have studied the properties of these proteins
      in epithelial MDCK cells in response to elevated intracellular calcium ion
      concentration, lowered pH, treatment with tumor promoter phorbol myristoyl
      acetate (PMA) and calmodulin inhibitor trifluoperazine (TFP). In untreated
      polarized MDCK cells annexin II was seen both along the lateral walls and
      membranes of intracellular vesicles, fodrin was located along the lateral walls,
      whereas PKC was seen in the cytoplasm. There was no observable translocation of
      these proteins upon elevation of the intracellular calcium concentration using a
      calcium ionophore A23187. On the other hand, treatment with TFP led to a release
      of annexin II from the plasma membranes which was accompanied by a transient peak
      in the intracellular calcium. Treatment with PMA led to a loss of the cubic form
      of the cells, a slight elevation in the intracellular calcium concentration and a
      drop in the intracellular pH. Simultaneously fodrin was released from the lateral
      walls, but still remained insoluble in Triton X-100, PKC became associated with
      the intracellular membranes and fibers, whereas annexin II remained along the
      lateral walls. These changes could be prevented by clamping the intracellular pH
      neutral during PMA treatment. On the other hand, lowering of intracellular pH
      below 6.5 with the nigericin treatment led to a similar translocation of fodrin
      and PKC as PMA. This suggests that the protein redistribution is caused by
      cytoplasmic acidification and is due to an increased hydrophobicity and enhanced
      protonation of lipids and proteins. In contrast, no changes were seen in the
      annexin II distribution in response to altered pH. Hence, its release by TFP is
      presumably due to changes in the cationic properties of the inner phase of the
      plasma membrane. Thus, proteins which show similar binding properties with
      liposomes show different characteristics in their association with the
      intracellular membranes.

PMID- 8305456
TI  - Cell-free transfer of phospholipids between the endoplasmic reticulum and the
      Golgi apparatus of leek seedlings.
AB  - The transfer of lipids between the endoplasmic reticulum and the Golgi apparatus
      was investigated in vitro using a cell-free system from leek seedlings. Lipids of
      the donor membranes (endoplasmic reticulum) were radiolabeled either by
      incubating leek seedlings with [1-14C]acetate or [3H]acetate. Acceptor membranes
      (Golgi apparatus) were unlabeled and immobilized on nitrocellulose strips. The
      assay measured the lipid transfer resulting from both an ATP-independent process
      and an ATP- and cytosol-dependent process. A significant ATP- and cytosol
      dependent lipid transfer was observed only in the case of the endoplasmic
      reticulum as donor and the Golgi apparatus as acceptor. Lipids transferred in an
      ATP-dependent manner were chiefly phosphatidylcholine, phosphatidylethanolamine
      and phosphatidylserine. The stimulation of lipid transfer by ATP as compared to
      the ATP-independent process was +79% (PC), +123% (PS) and +69% (PE). On the other
      hand, PI was not transferred in an ATP-dependent manner (the stimulation by ATP
      was only 20%). This supports the theory that a sorting of phospholipids takes
      place in the donor membrane. Moreover, a formation of lysoPC was observed only in
      the presence of ATP (+330%). The ATP-dependent lipid transfer was inhibited by N
      ethylmaleimide, indicating the involvement of cytosolic (but no phospholipid
      transfer proteins) or membrane proteins in the transfer process. The ATP
      dependent transfer of lipids was also diminished at 12 degrees C showing the
      sensitivity to low temperatures of the transfer of lipids between the endoplasmic
      reticulum and the Golgi apparatus.

PMID- 8305457
TI  - The solute permeability of thylakoid membranes is reduced by low concentrations
      of trehalose as a co-solute.
AB  - The different efficiencies of sucrose and trehalose in protecting isolated
      spinach (Spinacia oleracea L.) thylakoids against freeze-thaw damage is
      quantitatively related to their ability to reduce the solute loading of the
      vesicles during freezing. In the present paper we show that this effect is based
      on a reduction of the solute permeability of the membranes. Permeability was
      measured with 14C-labeled glucose at temperatures between 0 and 10 degrees C.
      Glucose permeability was reduced by both sucrose and trehalose, with trehalose
      effective at much lower concentrations than sucrose. An analysis of the
      temperature dependence of glucose permeability in the presence and absence of
      trehalose revealed that a 50% reduction in permeability resulted from a 10%
      increase in activation energy and a 30% decrease in activation entropy. Using the
      fluorescence probe 1,6-diphenyl-1,3,5-hexatriene (DPH), we found that the reduced
      permeability of the membranes in the presence of trehalose was unaccompanied by a
      reduction in lipid fluidity. This also excluded the possibility of a solute
      induced liquid crystalline to gel phase transition. A reduced partitioning of the
      hydrophobicity-sensitive dye merocyanine 540 into thylakoids and into membranes
      containing 50% digalactosyldiacylglycerol in the presence of trehalose as
      compared to sucrose and glucose showed that the lipid headgroup region of these
      membranes became less accessible for solutes. No significant difference in
      merocyanine partitioning in the presence of trehalose as compared to sucrose or
      glucose was apparent when monogalactosyldiacylglycerol dispersions or
      phosphatidylcholine vesicles were investigated.

PMID- 8305458
TI  - Steady-state fluorescence studies on lipase-vesicle interactions.
AB  - The interaction of lipase from Candida cylindracea (CCL) with positively charged
      polymerizable surfactant vesicles was studied by the use of steady-state
      fluorescence techniques. The phase transition of vesicles composed of
      nonpolymerized and polymerized N-allylbis[2-(hexadecanoyloxy)ethyl]methylammonium
      bromide (ABHEMA Br) was determined in the absence of lipase, by measuring the
      change in fluorescence anisotropy of the membrane probe 1,6-diphenyl-1,3,5
      hexatriene (DPH). The phase transition temperature for nonpolymerized vesicles is
      49 degrees C and for the polymerized analogues 45 degrees C. Fluorescence
      anisotropy and resonance energy transfer measurements were used to illustrate the
      incorporation of the lipase in the vesicle membrane. These studies demonstrated
      that CCL is incorporated into the hydrophobic bilayer of the vesicle. By using an
      interfacial membrane probe 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5
      hexatriene p-toluene sulphonate, TMA-DPH) and an internal membrane probe (DPH),
      it could be determined that the enzyme is incorporated more efficiently into
      nonpolymerized vesicles, and that the penetration of the enzyme into the bilayer
      is less deep in the case of the polymerized vesicles.

PMID- 8305459
TI  - Mechanistic studies of sterol carrier protein-2 effects on L-cell fibroblast
      plasma membrane sterol domains.
AB  - The factors which regulate intermembrane sterol domains and exchange in
      biomembranes are not well understood. A new fluorescent sterol exchange assay
      allowed correlation of changes in polarization to sterol transfer. Analysis of
      spontaneous sterol exchange between L-cell plasma membranes indicated two
      exchangeable and one very slowly or nonexchangeable sterol domain. The
      exchangeable domains exhibited half-times of 23 and 140 min with fractional
      contributions of 5 and 30%, respectively. Sterol carrier protein-2 (SCP-2)
      enhanced sterol exchange between L-cell plasma membranes and altered sterol
      domain size in a concentration dependent manner. Previous model membrane studies
      indicate that SCP-2 alters sterol domains and exchange through interaction with
      anionic phospholipids. In contrast to these observations, the ionic shielding
      agents KCl, low pH, or neomycin were either totally or partially ineffective
      inhibitors of SCP-2 action in L-cell plasma membrane exchanges. Thus the
      mechanism of SCP-2 in sterol transfer appears to be less charge dependent in L
      cell plasma membranes than in model membranes. The cholesterol lowering drug
      probucol was also capable of altering the sterol exchange kinetics.

PMID- 8305460
TI  - Transfer of pyrene-labelled diacyl-, alkylacyl-, and alkenylacyl
      glycerophospholipids from vesicles to human blood platelets.
AB  - The present study was aimed at investigating the spontaneous transfer of
      fluorescently labelled serine- and choline-glycerophospholipids from unilamellar
      vesicles to resting human blood platelets. The most effectively transferred
      phospholipids were pyrene-phosphatidylserine (PS) and the ether analogues of
      choline-glycerophospholipids, e.g., pyrene-alkylacyl- and pyrene-1'-alkenylacyl
      glycerophosphocholines (plasmalogens). Transfer of pyrene-diacyl
      glycerophosphocholine and pyrene-phosphatidic acid was almost not detectable
      under the same experimental conditions. The fast intermembrane PS-transfer could
      be explained by the very high degree of adsorption of PS donor vesicles to the
      platelet plasma membrane. The short halftime of transfer rate (12-14 min) and the
      high incorporation (1.08-2.16% of total platelet glycerophosphocholines) observed
      for ether choline-phospholipids in contrast to pyrene-PS (20 min, 0.8% of total
      platelet PS), could be interpreted in terms of their bulk membrane properties.

PMID- 8305461
TI  - The reconstituted carnitine carrier from rat liver mitochondria: evidence for a
      transport mechanism different from that of the other mitochondrial translocators.
AB  - The transport mechanism of the reconstituted carnitine carrier purified from rat
      liver mitochondria was investigated kinetically. The half-saturation constant
      (Km) for carnitine on the internal side of the liposomal membrane (8.7 mM) was
      found to be much higher than that determined for the external surface (0.45 mM).
      The exclusive presence of a single transport affinity for carnitine on each side
      of the membrane indicated a unidirectional insertion of the carnitine carrier
      into the proteoliposomes, most probably right-side-out with respect to
      mitochondria. Under these defined conditions bisubstrate initial velocity studies
      of homologous (carnitine/carnitine) and heterologous (carnitine/acylcarnitine)
      antiport were performed by varying both the internal and external substrate
      concentrations. The kinetic patterns obtained showed that the ratio Km/Vmax is
      not influenced by the second (non-varied) substrate, which indicates a ping-pong
      mechanism. The carnitine carrier thus differs from all other mitochondrial
      carriers analyzed so far in the reconstituted state, for which a common
      sequential type of reaction mechanism has been found.

PMID- 8305462
TI  - Interconversion of bilayer phase transition temperatures between
      phosphatidylethanolamines and phosphatidylcholines.
AB  - High-resolution differential scanning calorimetric studies were performed to
      investigate the thermotropic phase behavior of 31 molecular species of
      phosphatidylethanolamines in excess water. Upon reheating, the aqueous
      dispersions of these lipids undergo the gel to liquid-crystalline phase
      transitions at well defined temperatures (Tm). These Tm values were shown to
      relate to the structural parameters of the underlying lipid molecules in a
      characteristic manner. Based on these observations, an interconversion of the Tm
      values between saturated phosphatidylethanolamines and phosphatidylcholines is
      established quantitatively for the first time.

PMID- 8305463
TI  - Interaction of papaverine with micelles of surfactants with different charge
      studied by 1H-NMR.
AB  - The interaction of the vasodilator drug papaverine (PAV) with micelles of
      surfactants with different charge of headgroups as well as the properties of PAV
      in D2O solution were studied by 1H-NMR. At pD values above 6.4 deprotonated PAV
      molecules tend to precipitate, the signals of the heterocycle protons of
      solubilized PAV molecules being shifted to high field. At PAV concentration above
      1 mM its protons experience upfield shifts which increase with pD value and are
      due to the stacking of aromatic rings. Incorporation into micelles caused shifts
      of all resonances. This effect is due to changes in the local chemical
      environment of PAV rather than to stacking, and, possibly, involves the
      deprotonation of the N atom of PAV heterocycle. Line broadening of PAV protons at
      the molar ratio surfactant/PAV > 16 indicated their restricted mobility.
      Different complexes were formed due to interaction between the heterocycle of PAV
      and polar headgroups of cationic cetyltrimethylammonium chloride (CTAC) or
      anionic sodium dodecylsulfate (SDS). The binding of PAV to zwitterionic N
      hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS) is similar to that of
      PAV to CTAC. Association constants were estimated from NMR data as 20, 60 and 350
      M-1 at pD = 4.9 +/- 0.1 for HPS, CTAC and SDS, respectively. Thus, the mode of
      binding of PAV to HPS is defined by the cationic dimethylammonium headgroup
      fragment, whereas the negative fragment attenuates the effective charge of HPS
      headgroup.

PMID- 8305464
TI  - Adsorption of Ca2+ and La3+ to bilayer membranes: measurement of the adsorption
      enthalpy and binding constant with titration calorimetry.
AB  - The adsorption of Ca2+ and La3+ ions to the surface of lipid bilayer membranes
      was studied with high sensitivity titration calorimetry. Ca2+ adsorbs to mixed
      phosphatidylcholine/phosphatidylglycerol membranes with a reaction enthalpy of
      delta H approximately 0.1-0.2 kcal/mol. La3+ binds to sonified
      phosphatidylcholine vesicles with a reaction enthalpy of delta H approximately
      +1.8 kcal/mol. Adsorption of La3+ to phosphatidylcholine bilayers imparts a net
      positive charge to the membrane surface which makes the binding of further La3+
      increasingly more difficult. From the decreasing amplitudes in the calorimetric
      titration experiment a La3+ adsorption constant of K approximately (4.1 +/- 1.1)
      x 10(3) M-1 was evaluated. Electrostatic effects were corrected for by means of
      the Gouy-Chapman theory. The adsorption constant of Ca2+ was determined
      previously as K approximately 10-20 M-1 using the same binding model. Since the
      reaction enthalpies of Ca2+ and La3+ adsorption are endothermic, the adsorption
      of both metal ions to the membrane surface is driven by a distinct change in
      entropy.

PMID- 8305465
TI  - Asymmetric black membranes formed by one monolayer of bipolar lipids at the
      air/water interface.
AB  - In this work a new technique is presented for the formation of black lipid
      membranes from a single monolayer of bipolar lipids at the air/water interface.
      The lipid, extracted from the thermophilic archaeobacterium Sulfolobus
      solfataricus, is characterized by two different polar heads. The membrane is
      formed with a technique similar to that introduced by Montal and Mueller;
      however, the lipid is spread only on one side of the teflon partition.
      Conductance in the presence of valinomycin, voltage-dependent capacitance,
      current-voltage measurements and electroporation indicate that, as expected, the
      membrane is asymmetric.

PMID- 8305466
TI  - Purification and characterization of an aminopeptidase from tuna (Thunnus
      albacares) pyloric caeca.
AB  - An aminopeptidase was purified from a water soluble fraction of tuna pyloric
      caeca by heat treatment, Zn2+ fractionation, ion exchange on a DEAE cellulose
      column, gel filtration on Fractogel TSK-55, and immobilized metal ion affinity
      chromatography (IMAC) on IDA(Cu2+/Zn2+)-Sepharose 6B. The molecular mass of the
      enzyme was estimated to be 150,000 on Sephacryl S-300 HR, and was found to be
      near 72,000 by SDS-PAGE. The aminopeptidase, which is a glycoprotein rich in
      acidic amino acids, is optimally active at pH 8.8 and 65 degrees C. The enzyme
      activity was not affected by Mg2+, Zn2+, Ca2+, Mn2+, Co2+, PMSF, iPr2FP, 4
      hydroxymercuribenzoic acid, iodoacetamide, puromycin, and cysteine but it was
      strongly inhibited by metal chelators (EDTA and o-phenanthroline), amastatin,
      Hg2+, Cd2+, and Cu2+. The enzyme was also inhibited by some L-amino acids.
      Kinetic parameters of the enzyme were determined with some aminoacyl-p
      nitroanilides and aminoacyl-beta-naphthylamides. L-Alanine-p-nitroanilide and L
      alanine-beta-naphthylamide were hydrolysed most rapidly while the highest
      hydrolytic coefficient (kcat/Km) value was obtained with L-methionine-p
      nitroanilide. The apoaminopeptidase was prepared and reconstitution of an active
      enzyme was carried out using metal chelating interaction chromatography on an IDA
      Sepharose 6B column charged with a metal ion. Full activity was restored with
      Zn2+, Co2+, Cu2+ and Al3+. Zn(2+)-Enzyme was the most thermostable form of the
      aminopeptidase. Reversal inhibition by Cu2+ and Cd2+ was also examined. When the
      aminopeptidase was partially deglycosylated by a treatment with N-glycosidase F
      some of its physical properties differed from that of the native enzyme: its
      electrophoretic mobility was reduced and its stability to denaturation by SDS and
      by ionic strength were lower than those of the untreated enzyme. All together,
      our results indicate that the tuna pyloric caeca aminopeptidase is distinct from
      the peptide hydrolases characterized in the literature.

PMID- 8305468
TI  - Competing peroxidase and oxidase reactions in scopoletin-dependent H2O2-initiated
      oxidation of NADH by horseradish peroxidase.
AB  - Addition of NADH inhibited the peroxidative loss of scopoletin in presence of
      horseradish peroxidase and H2O2 and decreased the ratio of scopoletin
      (consumed):H2O2 (added). Concomitantly NADH was oxidized and oxygen was consumed
      with a stoichiometry of NADH:O2 of 2:1. On step-wise addition of a small
      concentration of H2O2 a high rate of NADH oxidation was obtained for a
      progressively decreasing time period followed by termination of the reaction with
      NADH:H2O2 ratio decreasing from about 40 to 10. The rate of NADH oxidation
      increased linearly with increase in scopoletin concentration. Other phenolic
      compounds including p-coumarate also supported this reaction to a variable
      degree. A 418-nm absorbing compound accumulated during oxidation of NADH. The
      effectiveness of a small concentration of H2O2 in supporting NADH oxidation
      increased in presence of SOD and decreased in presence of cytochrome c, but the
      reaction terminated even in their presence. The results indicate that the
      peroxidase is not continuously generating H2O2 during scopoletin-mediated NADH
      oxidation and that both peroxidase and oxidase reactions occur simultaneously
      competing for an active form of the enzyme.

PMID- 8305467
TI  - Characteristic properties of retinal oxidase (retinoic acid synthase) from rabbit
      hepatocytes.
AB  - Retinal oxidase (retinoic acid synthase) (EC 1.2.3.11) was purified
      electrophoretically, as a single protein band, from rabbit liver cytosol. The
      characteristic properties, enzymatic reaction mechanism, substrate specificity
      and kinetic parameters for retinals and molecular oxygen of the retinal oxidase
      were investigated. The Km values for all-trans-retinal of the retinal oxidase was
      the lowest than those for the other retinal derivatives. The retinal oxidase is a
      metalloflavoenzyme containing 2 FADs as the coenzyme, and 8 irons, 2 molybdenums,
      2 disulfide bonds and 8 inorganic sulfurs. Its relative molecular mass was
      determined to be 270 kDa by gel filtration HPLC on a TSKgel G3000swXL column. Its
      minimum molecular mass was estimated to be 135 kDa by SDS-PAGE. The optical
      spectrum of the retinal oxidase showed absorption peaks at 275, 340 and 450 nm,
      and shoulders at 420 and 473 nm, in the oxidized form. The molecular extinction
      coefficients of the oxidase at selected wavelengths were determined. Circular
      dichroism spectra of the retinal oxidase were measured in the ultraviolet and
      visible regions. These spectra showed positive absorption in the visible region.
      The amino-acid composition was determined. The activity of the oxidase was not
      affected by any cofactors, such as NADP+, NAD+, NADPH and NADH, and it did not
      occur under anaerobic conditions. The oxidase was not inhibited by BOF-4272, a
      potent inhibitor of xanthine dehydrogenase, or rat anti-xanthine dehydrogenase
      IgG. Experiments on retinoic acid formation under 18O2 or H2(18)O demonstrated
      that the oxygen of water was incorporated into retinoic acid by the retinal
      oxidase, but not molecular oxygen.

PMID- 8305469
TI  - Infrared spectroscopic studies of calcium binding to inhibited beta-trypsins.
AB  - Fourier transform infrared spectroscopy was used to examine the effect of calcium
      binding on the secondary structure of two inhibited bovine beta-trypsins. Neither
      the diisopropyl fluorophosphate- nor benzamidine-inhibited forms showed
      detectable secondary structure perturbation upon calcium binding at pD 6.9 and
      5.0, respectively. Considered in light of the recent assignment of an amide I'
      band to the autolysis loop of bovine beta-trypsin, these results contradict the
      generally held hypothesis that calcium slows trypsin autolysis by induction of a
      conformational change at this site and support the recent contention that the
      mechanism of action has a specific electrostatic origin. In addition, the
      appearance of a band at 1699 cm-1 in the benzamidine-inhibited form can be
      interpreted as resulting from the NC-N stretching vibrations of the amidinium
      moiety, which the observed crystal structure indicates is hydrogen-bonded to the
      carboxyl group of active-site Asp-189.

PMID- 8305470
TI  - 1H- and 15N-NMR study of the binding of thiocyanate to chemically modified
      horseradish peroxidase and involvement of salt bridge.
AB  - The chemical modification of native horseradish peroxidase (HRP) has been carried
      out by esterification of the heme propionic group. 15N- and 1H-NMR studies on
      binding of thiocyanate ion to chemically modified HRP have been utilized to
      demonstrate the existence of salt bridge between the heme propionic acid and
      distal amino acid group. The catalyzed oxidation of thiocyanate by the native
      HRP, and the chemically modified HRP has also been studied at different pH, and
      the significance of the salt bridge discussed.

PMID- 8305471
TI  - A 13C solid-state NMR study of the structure and auto-oxidation process of
      natural and synthetic melanins.
AB  - This paper presents a 13C CP/MAS NMR study of the melanin pigments obtained
      through natural and synthetic origins: sepia-melanin from squid ink and three
      synthetic 5,6-dihydroxyindole-melanins prepared using different non-enzymatic
      oxidation pathways. The synthetic pigments can be distinguished from natural
      melanin by the absence of aliphatic carbons, thereby confirming the unreacted 3,4
      dihydroxyphenylalanine and the proteinaceous origins of the aliphatic resonances
      in natural eumelanin. The spectra of selected non-protonated carbon resonances
      and those with only protonated carbon signals led to a quantitative analysis. An
      auto-oxidative experiment using a synthetic melanin, over a period of 130 h, has
      shown an unusually slow disappearance of hydrogen peroxide formed in situ. The
      13C-NMR spectrum of the insoluble oxidized synthetic melanin compared to that
      before auto-oxidation clearly demonstrates that the oxidation process is
      associated with chemical changes within the pigment; i.e., carbonyl functional
      group formation and an increase of the non-protonated carbons fraction.

PMID- 8305472
TI  - Mini-myoglobin: native-like folding of the NO-derivative.
AB  - Mini-myoglobin is a polypeptide fragment (residues 32-139) obtained by limited
      proteolysis of horse heart apomyoglobin and reconstituted with the natural heme.
      Its functional properties are very similar to those of native myoglobin and
      therefore it may represent a model for testing the functional role of the protein
      fragment encoded by the central exon of myoglobin gene (residues 31-105). Here we
      have investigated some properties of the nitric oxide derivative of mini
      myoglobin in comparison with those of NO-myoglobin, to provide more structural
      information on the heme pocket residues in addition to that already acquired by
      electron paramagnetic resonance of the cobalt-substituted mini-myoglobin. At pH
      7.0, optical and circular dichroism Soret spectra, as well as electron
      paramagnetic resonance spectra reveal that the heme orientation in the pocket and
      the coordination state of the ferrous iron in NO-mini-myoglobin are similar to
      those of the whole protein. The spectra of the NO-mini-myoglobin complex are very
      sensitive to pH changes at variance to what is observed for the NO-myoglobin
      derivative in the same pH range (5.5-9.5). In particular, increasing or
      decreasing pH from 7.0, results in a decrease of the extinction coefficient and
      of the ellipticity in the Soret region and in a change of the shape of the
      electron paramagnetic resonance signal. The spectral changes are diagnostic for a
      transition from a hexa-coordinated (at pH 7.0) to a penta-coordinated heme (at pH
      5.5 or 9.5), with the proximal histidine-iron bond either broken or stretched
      dramatically. Thus, although mini-myoglobin is able to bind NO in a geometry
      similar to that of the native protein, the resulting NO derivative shows a much
      higher pH dependence, suggesting that the two lacking side domains are mainly
      involved in enhancing the stability of the hemoprotein core.

PMID- 8305473
TI  - Tyrosinase: kinetic analysis of the transient phase and the steady state.
AB  - The transient phase of tyrosinase activity acting on monophenols has been
      investigated. Although an analytical solution for the lag period (tau) cannot be
      obtained, its dependence on reagent concentration and pH is studied. It is
      established that decreases as the quantity of enzyme increases, although it
      increases when monophenol or pH are increased. The computer simulation shows
      those rate constants whose variations affect the transient phase most
      significantly. In addition, the steady state of the pathway is studied using
      tyrosinases from several sources such as mushroom, frog epidermis and grape. The
      kinetic analysis, which is based on not imposing restrictions on the values of
      the rate constants involved in the mechanism, allows us to obtain analytical
      expressions for both monophenolase and diphenolase activities and explains the
      experimental results obtained with the different enzymes. The values determined
      for the kinetic parameter, R, point to the monophenol hydroxylation step as being
      the limiting step of the turnover, while the values obtained for n suggest the
      absence of fast equilibrium in the oxidation of diphenol by Emet.

PMID- 8305474
TI  - Elastase inhibition by the C-terminal domains of alpha-crystallin and small heat
      shock protein.
AB  - alpha-Crystallin, an abundant eye-lens protein and a stress protein in other
      tissues, shows structural and functional similarities with the small heat-shock
      proteins. One of the properties in common is the inhibition of elastase. We now
      report that the separated subunits of alpha-crystallin, alpha A and alpha B, also
      exhibit elastase inhibition, whereas phosphorylation of these subunits apparently
      has no influence on the inhibitory capacity. Furthermore, for both alpha A
      crystallin and mouse HSP25 the putative C-terminal structural domain, comprising
      the major region of homology between these proteins, is sufficient to give
      elastase inhibition. With database search no homology could be found between the
      three proteins under investigation and any of the known consensus sequences of
      proteinase inhibitor families.

PMID- 8305475
TI  - Dopachrome tautomerase decreases the binding of indolic melanogenesis
      intermediates to proteins.
AB  - Dopachrome tautomerase (DCT) is a recently characterized enzyme contributing to
      the control of melanogenesis in mammals. The enzyme catalyzes the rearrangement
      of L-Dopachrome (L-DC) to 5,6-dihydroxyindole 2-carboxylic acid (DHICA), while
      the spontaneous rearrangement of L-DC leads to 5,6-dihydroxyindole (DHI). Due to
      the lower reactivity of DHICA in comparison to DHI, DCT could provide a
      protective mechanism against the cytotoxicity of decarboxylated indolic
      melanogenic intermediates by limiting the formation of these highly reactive
      decarboxylated species within melanocytes. We have followed the binding of
      radioactive melanogenic precursors to a model protein, bovine serum albumin
      (BSA). Using L-DC as initial melanin precursor, this binding was decreased by DCT
      in a concentration-dependent manner. In the presence of tyrosinase, the binding
      of L-Dopa-derived intermediates to BSA was also decreased by DCT and the
      percentage of decrease was even higher than using L-DC as initial melanin
      precursor. SDS-PAGE followed by fluorographic detection of radioactive bands
      showed the formation of covalent adducts between BSA and melanin precursors, as
      well as of aggregated forms of this protein. This aggregation was also diminished
      by DCT. These data indicate that DCT could play a protective role against the
      cytotoxic action of decarboxylated indoles within mammalian melanocytes.

PMID- 8305476
TI  - The complete primary structure of the long form of mouse alpha 1(IX) collagen
      chain and its expression during limb development.
AB  - Type IX collagen is a newly discovered collagen molecule that is associated with
      Type II-containing collagen fibrils in cartilage, vitreous and embryonic cornea.
      It consists of three distinct chains: alpha 1(IX), alpha 2(IX) and alpha 3(IX).
      The alpha 1(IX) chain has been to be synthesized in two different forms, which
      are generated by alternative transcription and splicing. In this manuscript we
      describe the isolation and sequencing of a cDNA coding for the entire coding
      region of the long form of mouse alpha 1(IX) chain. Nucleotide sequence analysis
      of this cDNA determined for the first time the primary structure of the entire
      long form of the mouse alpha 1(IX) chain. RT-PCR was used to examine collagen
      gene expression during limb development from day 10 to 18 in mouse embryos.
      Collagen I and II mRNA levels gradually increased all through the developmental
      stages. Collagen X expression increased further after day 16 in limb development,
      whereas the alpha 1(IX)mRNA level dropped at this time. This could be due to
      active bone formation relative to cartilage synthesis in the embryonic limb bud
      around day 16 in mouse development.

PMID- 8305477
TI  - Primary structure and specificity of the major serine proteinase inhibitor of
      amaranth (Amaranthus caudatus L.) seeds.
AB  - A novel member of the potato inhibitor I family of serine proteinase inactivating
      proteins has been isolated from seeds of grain amaranth (Amaranthus caudatus L.)
      and characterized. The mature form of the amaranth trypsin/subtilisin inhibitor
      (ATSI) with pI approximately 8.3 and molecular mass 7887 Da contains 69 amino
      acids in a sequence showing 33-51% identity with members of the inhibitor I
      family from other plant families. A minor form with pI approximately 7.8 and same
      inhibitory properties lacked the N-terminal dipeptide Ala-Arg. In accordance with
      the reactive-site bond Lys45-Asp46, which was identified by specific cleavage on
      a subtilisin column, ATSI is a potent inhibitor of trypsin (Ki approximately 0.34
      nM) and more weakly of plasmin (Ki approximately 38 nM) and Factor XIIa (Ki
      approximately 440 nM). However, ATSI also inactivates chymotrypsin (Ki
      approximately 0.41 nM), cathepsin G (Ki approximately 122 nM) and several
      alkaline microbial proteinases, including subtilisin NOVO (Ki approximately 0.37
      nM). Interestingly, ATSI contains a Trp residue instead of the highly conserved
      Arg in position 53 (P8'), which is assumed to play a central role in
      stabilization of the active-site loop during complex formation. ATSI was
      immediately inactivated by pepsin and hardly represents an antinutritional
      component in foods or feeds.

PMID- 8305478
TI  - The primary structure of sheep liver cytosolic serine hydroxymethyltransferase
      and an analysis of the evolutionary relationships among serine
      hydroxymethyltransferases.
AB  - The complete amino-acid sequence of sheep liver cytosolic serine
      hydroxymethyltransferase was determined from an analysis of tryptic,
      chymotryptic, CNBr and hydroxylamine peptides. Each subunit of sheep liver serine
      hydroxymethyltransferase consisted of 483 amino-acid residues. A comparison of
      this sequence with 8 other serine hydroxymethyltransferases revealed that a
      possible gene duplication event could have occurred after the divergence of
      animals and fungi. This analysis also showed independent duplication of SHMT
      genes in Neurospora crassa. At the secondary structural level, all the serine
      hydroxymethyltransferases belong to the alpha/beta category of proteins. The
      predicted secondary structure of sheep liver serine hydroxymethyltransferase was
      similar to that of the observed structure of tryptophan synthase, another
      pyridoxal 5'-phosphate containing enzyme, suggesting that sheep liver serine
      hydroxymethyltransferase might have a similar pyridoxal 5'-phosphate binding
      domain. In addition, a conserved glycine rich region, G L Q G G P, was identified
      in all the serine hydroxymethyltransferases and could be important in pyridoxal
      5'-phosphate binding. A comparison of the cytosolic serine
      hydroxymethyltransferases from rabbit and sheep liver with other proteins
      sequenced from both these sources showed that serine hydroxymethyltransferase was
      a highly conserved protein. It was slightly less conserved than cytochrome c but
      better conserved than myoglobin, both of which are well known evolutionary
      markers. C67 and C203 were specifically protected by pyridoxal 5'-phosphate
      against modification with [14C]iodoacetic acid, while C247 and C261 were buried
      in the native serine hydroxymethyltransferase. However, the cysteines are not
      conserved among the various serine hydroxymethyltransferases. The exact role of
      the cysteines in the reaction catalyzed by serine hydroxymethyltransferase
      remains to be elucidated.

PMID- 8305479
TI  - Putative functions of phenylalanine-350 of Pseudomonas putida cytochrome P
      450cam.
AB  - Cytochrome P-450cam hydroxylates d-camphor, using molecular oxygen and reducing
      equivalents transferred via putidaredoxin. We constructed mutant genes in which
      Phe-350 of P-450cam was replaced by Leu, Tyr, or His by site-directed
      mutagenesis, expressed them in Escherichia coli, purified the mutant proteins,
      and compared their enzymic properties with those of the wild type P-450cam. NADH
      oxidation rate of the Tyr mutant in the reconstituted system with putidaredoxin
      and putidaredoxin reductase was similar to that of the wild type enzyme, while
      the Leu mutant and the His mutant showed 67% and 17% activity of that of the wild
      type, respectively. The affinities of these mutant proteins for camphor and the
      oxidized form of putidaredoxin were much the same as those of the wild type
      protein. Rate constants for the reduction reaction of P-450cam by reduced
      putidaredoxin, a physiological electron donor for P-450cam, of Tyr and His
      mutants were much the same as that of the wild type enzyme, whereas the Leu
      mutant showed approx. half that of the wild type. Thus, the aromatic ring of Phe
      350 of P-450cam probably contributes to enhancing efficiency of the electron
      transfer yet does not seem to be essential for the reaction.

PMID- 8305480
TI  - S'-subsite mapping of polyethylene glycol-modified alpha-chymotrypsin and alpha
      chymotrypsin: a comparative study.
AB  - Nucleophile specificities of polyethylene glycol-modified alpha-chymotrypsin and
      the native enzyme were investigated via acyl transfer reactions using Ac-Tyr-OEt
      as acyl donor and a large series of peptides and amino-acid amides as
      nucleophiles. In acyl transfer reactions with amino-acid amides both enzymes
      prefer basic and bulky amino-acid residues. However, peptides with bulky
      aliphatic or aromatic residues in P1' position were very poor nucleophiles for
      both enzymes. Surprisingly, peptides having bulky aliphatic or aromatic residues
      in P2' were preferred by the modified enzyme and were apparently more efficient
      nucleophiles for both enzymes than those with such residues in P1'. Generally,
      peptides with a longer chain were weaker nucleophiles in the reactions catalyzed
      by polyethylene glycol-modified enzyme. In the series of peptides containing a
      positively charged amino-acid residue in various locations, the order of
      nucleophilic efficiency is with this location being: P1' > P3' > P2'; this is
      valid for both enzymes.

PMID- 8305481
TI  - Characteristics of 92 kDa type IV collagenase/gelatinase produced by granulocytic
      leukemia cells: structure, expression of cDNA in E. coli and enzymic properties.
AB  - Human neutrophils can be triggered to release the collagenolytic metalloenzymes,
      interstitial collagenase and 92 kDa type IV collagenase/gelatinase. We have
      isolated and sequenced a 2.3 kb cDNA from a chronic granulocytic leukemia cDNA
      library that encodes for human neutrophil type IV collagenase. With the exception
      of one amino-acid substitution at position 280 (Arg-->Gln), the deduced amino
      acid sequences of neutrophil gelatinase are identical to the amino-acid sequences
      of the enzyme isolated from fibrosarcoma cells. Expression of the cDNA in E. coli
      yielded a 72 kDa protein having a gelatinolytic activity on zymogram gel. The
      recombinant enzyme was activated with APMA and trypsin. The activation was
      accompanied by a reduction in molecular weight of approximately 10 kDa; such a
      reduction is characteristic of matrix metalloproteinases. The recombinant
      gelatinase cleaved native type V and XI collagens. Native type I collagen was not
      a substrate for the enzyme. These data suggest that native and recombinant 92 kDa
      type IV collagenase produced in E. coli have similar biochemical properties. The
      successful expression of the collagenase in a prokaryotic system will greatly
      facilitate the structure-function characterization of the enzyme and allow a more
      precise analysis of its physiological and pathological roles.

PMID- 8305482
TI  - Interaction of bile acids and cholesterol with non-systemic agents having
      hypocholesterolemic properties.

PMID- 8305483
TI  - Arachidonate 15-lipoxygenase in human corneal epithelium and 12- and 15
      lipoxygenases in bovine corneal epithelium: comparison with other bovine 12
      lipoxygenases.
AB  - Lipoxygenases of bovine and human corneal epithelia were investigated. The bovine
      epithelium contained an arachidonate 12-lipoxygenase and a 15-lipoxygenase. The
      12-lipoxygenase was found in the microsomal fraction, while the 15-lipoxygenase
      was mainly present in the cytosol (100,000 x g supernatant). 12S
      Hydroxyeicosatetraenoic acid (12S-HETE) and 15S-hydroxyeicosatetraenoic acid (15S
      HETE) were identified by GC-MS and chiral HPLC. BW A4C, an acetohydroxamic acid
      lipoxygenase inhibitor, reduced the biosynthesis of 12S-HETE and 15S-HETE by over
      90% at 10 microM. IC50 for the 12-lipoxygenase was 0.3 microM. The bovine corneal
      12-lipoxygenase was compared with the 12-lipoxygenases of bovine platelets and
      leukocytes. All three enzymes metabolized 14C-labelled linoleic acid and alpha
      linolenic acid poorly (5-16%) in comparison with [14C]arachidonic acid.
      [14C]Docosahexaenoic acid and [14C]4,7,10,13,16-docosapentaenoic acid appeared to
      be less efficiently converted by the corneal enzyme than by the platelet and
      leukocyte enzymes. Immunohistochemical analysis of the bovine corneal epithelium
      using a polyclonal antibody against porcine leukocyte 12-lipoxygenase gave
      positive staining. The cytosol of human corneal epithelium converted
      [14C]arachidonic acid to one prominent metabolite. The product co-chromatographed
      with 15S-HETE on reverse phase HPLC, straight phase HPLC and chiral HPLC. Our
      results suggest that human corneal epithelium contains a 15-lipoxygenase and that
      bovine corneal epithelium contains both a 15-lipoxygenase and a 12-lipoxygenase.
      The corneal 12-lipoxygenase appears to differ catalytically from earlier
      described bovine 12-lipoxygenases.

PMID- 8305484
TI  - Surfactant proteins A (SP-A) and D (SP-D): levels in human amniotic fluid and
      localization in the fetal membranes.
AB  - Surfactant proteins A (SP-A) and D (SP-D) are major proteins, in the lung, which
      are composed of collagenous and globular domains. They show an overall similarity
      to the serum complement protein Clq, which is involved in the initiation of
      antibody-dependent defence mechanisms. Both SP-A and SP-D were detected,
      immunochemically, in amniotic fluid as early as 26 weeks gestation and, as
      expected, SP-A levels rose sharply from 32 weeks towards term. By contrast, SP-D
      levels in the same samples rose only moderately. Immunochemistry of paraffin
      sections of fetal membranes, revealed the presence of both SP-A and SP-D in the
      amniotic epithelium and chorio-decidual layers. SP-A and SP-D are both lectins
      and therefore they may play a role in the antibody-independent recognition and
      clearance of pathogens in the amniotic fluid.

PMID- 8305485
TI  - Site-directed mutagenesis studies on the iron-binding domain and the determinant
      for the substrate oxygenation site of porcine leukocyte arachidonate 12
      lipoxygenase.
AB  - cDNA for arachidonate 12-lipoxygenase of porcine leukocytes was expressed in
      Escherichia coli. The recombinant 12-lipoxygenase was purified by immunoaffinity
      chromatography to near homogeneity with a specific activity of about 1.5
      mumol/min per mg protein. Each of eight histidine residues, which were well
      conserved among various mammalian lipoxygenases and presumed as ligands for non
      heme iron, was substituted with leucine by site-directed mutagenesis. Each mutant
      enzyme was immunoaffinity-purified to near homogeneity. Mutations of His-361, 
      366 and -541 caused a total loss of enzyme activity, and the iron content was
      much lower (0.10, 0.06 and 0.06 g atom/mol protein) than that of the wild-type
      enzyme (0.53). Mutations of His-128 and -356 gave 159% and 162% specific activity
      of the wild-type enzyme, and the iron contents were 0.55 and 0.52 g atom/mol
      protein. Substitution of His-426 decreased the activity to 5%, but the iron
      content was 0.4 g atom/mol protein. The expression level of mutants at His-384
      and -393 was too low to precisely determine the iron content. Taken together, His
      361, -366 and -541 may play important roles for iron-binding in catalytically
      active 12-lipoxygenase. Since a high homology of amino acid sequence was known
      between porcine leukocyte 12-lipoxygenase and mammalian 15-lipoxygenases, we
      attempted to convert the 12-lipoxygenase to a 15-lipoxygenase. A double mutation
      of Val-418 and -419 to Ile and Met increased the ratio of 15- and 12-lipoxygenase
      activities from 0.1 to 5.7.

PMID- 8305486
TI  - Purification and properties of the squalene-hopene cyclase from Rhodopseudomonas
      palustris, a purple non-sulfur bacterium producing hopanoids and tetrahymanol.
AB  - The squalene-hopene cyclase of the hopanoid- and tetrahymanol-producing
      Rhodopseudomonas palustris was released from the isolated membranes by CHAPS and
      purified to homogeneity by successive chromatography on DEAE Sephacel, Octyl
      Sepharose, and Blue Sepharose. The enzyme has a molecular weight of 70 kDa as
      determined by SDS-PAGE and an isoelectric point at about pH 5.0. The enzyme
      activity has a maximum at 30 degrees C and at pH 6.5. No production of
      tetrahymanol could be demonstrated by using either crude or purified cyclase
      preparations.

PMID- 8305488
TI  - Reduced hepatic release of apoprotein B after enteral nutrition in rats.
AB  - To investigate the effects of enteral and parenteral alimentation on VLDL release
      from the liver, a lipid-free liquid nutriment was continuously administered to
      free-moving rats via the oral cavity (oral group), stomach (enteral group) or
      superior caval vein (parenteral group). After 1-week of nutrition, the plasma
      VLDL concentrations were significantly lowered in the enterally-fed group. By
      immunoblotting assay using a specific antiserum, plasma contents of both
      apoprotein B-100 and B-48, the major components of rat apoprotein B, were found
      to be decreased in the enteral group, whereas only that of apoprotein B-48 was
      reduced in the parenteral group as compared with the oral group. Sucrose gradient
      centrifugation of the lipid droplets in the liver from the enteral group showed
      an increase of the free-triacylglycerol fraction with a concomitant increase of
      the apoprotein B-48-rich triacylglycerol fraction. These results suggest that
      enteral nutrition causes triacylglycerol accumulation in the liver, at least in
      part by impairment of lipoprotein release from the liver.

PMID- 8305487
TI  - Ketoconazole and 25-hydroxycholesterol produce reciprocal changes in the rate of
      transcription of the human LDL receptor gene.
AB  - Sterol-dependent regulation of low-density lipoprotein (LDL) receptor gene
      expression was studied in the human hepatoma HepG2 cell line. Incubation of HepG2
      cells with 20 microM ketoconazole increased the level of LDL receptor mRNA. After
      a lag of approx. 1.0 h the level rose 6.5-fold within 8.0 h and remained elevated
      for up to 24 h. Incubation with 10 micrograms 25-hydroxycholesterol/ml for 24 h
      produced a 40-50% reduction in the level of LDL receptor mRNA. Ketoconazole- and
      25-hydroxycholesterol-induced changes in LDL receptor mRNA accumulation were due
      to alterations in the relative rate of LDL receptor gene transcription as
      measured by nuclear run-on transcription. Incubation with 20 microM ketoconazole
      for 4 h or 10 micrograms 25-hydroxycholesterol/ml for 24 h produced a 3.6-fold
      increase and a 40% reduction, respectively, in the transcription rate of LDL
      receptor gene. Removal of the Alu-like sequence elements within the LDL receptor
      cDNA was required to consistently measure changes in LDL receptor gene
      transcription. No significant changes were noted in the half-life of LDL receptor
      mRNA in ketoconazole or 25-hydroxycholesterol-treated cells. These data
      demonstrate that sterol-dependent changes in the level of LDL receptor mRNA can
      be completely accounted for by changes in the rate of LDL receptor gene
      transcription.

PMID- 8305489
TI  - Regulation of CTP: phosphocholine cytidylyltransferase in HepG2 cells: effect of
      choline depletion on phosphorylation, translocation and phosphatidylcholine
      levels.
AB  - We studied the effect of choline depletion on the biosynthesis of
      phosphatidylcholine (PC) and the distribution and phosphorylation of
      cytidylyltransferase (CT) in HepG2 cells. Phosphocholine concentrations decreased
      within 24 h of choline depletion to values less than 2% of controls. The
      incorporation of [3H]glycerol into PC was reduced in choline-depleted (CD) cells.
      The apparent turnover of PC was similar in CD and choline-supplemented (CS) cells
      (T1/2 = 20 h). The methylation pathway for PC synthesis increased nearly 10-fold
      in CD cells. Cell growth was similar in CD and CS cells. Over 95% of CT activity
      in CS cells was in the soluble pool. Choline depletion resulted in a progressive
      decrease in CT activity and immunodetected enzyme in the soluble pool and a
      corresponding increase in membrane CT over a 48-h period. Choline supplementation
      of CD cells caused a rapid release of membrane CT (complete release by 3 h). Two
      phosphorylated forms of CT were identified. One form contained a higher level of
      phosphorylation (HPCT) than the other form (LPCT). HPCT migrated slightly slower
      than LPCT on SDS gels. CD cells contained only LPCT in both soluble and membrane
      pools. CS cells contained only HPCT. During choline depletion PC content
      decreased nearly 20% but CT binding did not occur until LPCT was generated in
      cytosol. Conversely, choline supplementation released LPCT into cytosol and HPCT
      was formed only after the release. We conclude that both the induction of binding
      sites, perhaps by depletion of PC and dephosphorylation of HPCT to LPCT, are
      required for CT translocation to membranes. The release of CT from membranes is
      initiated by changes in membrane binding sites followed by trapping of the CT in
      the soluble pool by phosphorylation of LPCT to HPCT.

PMID- 8305490
TI  - Gestational age dependence of 11 beta-hydroxysteroid dehydrogenase and its
      relationship to the enzymes of phosphatidylcholine synthesis in lung and liver of
      fetal rat.
AB  - Increase in fetal surfactant synthesis and lung maturity is caused by the
      glucocorticoidal induction of enzymes required for phosphatidylcholine (PC)
      synthesis towards the end of gestation. The regulation of gestational age
      dependent induction of PC synthesis by glucocorticoids is still unclear. Since 11
      beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity and its metabolising
      capacity for glucocorticoids have been suggested to play a central role in this
      regulation, we measured the gestational age-dependent changes in 11 beta-HSD and
      PC synthesizing enzymes in lung and liver of fetal rat. The activity of
      cholinephosphate cytidyltransferase (CCT; key enzyme in PC synthesis), choline
      phosphotransferase (CPT) and lysolecithin acyltransferase (LAT) were found to
      increase gradually in the lung towards the end of gestation, reached peak values
      at term followed by a decrease of activity reaching finally adult levels. Only CK
      activity exhibited constant levels until term followed by a slight increase after
      the birth. In comparison with the lung, the liver enzymes followed a similar
      pattern, but at a higher rate of activity except for CCT which was higher in the
      lung. The activity of 11 beta-HSD in fetal lung microsomes was detectable from
      day 20 and increased towards the end of gestation in the lung and liver of the
      rat. Oxidase activity was always found to exceed the reductase activity. The
      activity of 11 beta-HSD continued to increase after delivery and reached peak
      levels in adult animals in both organs. In order to test the hypothesis, whether
      11 beta-HSD activity and PC synthesis are induced by increasing endogenous
      glucocorticoidal levels, we examined on day 19 of gestation the effect of
      dexamethasone (DEXA) on enzymatic activities (11 beta-HSD, CCT) and on
      [14C]choline incorporation in phosphatidylcholine in fetal lung organoid
      cultures. Additionally, changes in CCT activity in fetal lungs after maternal
      administration of DEXA were measured. DEXA accelerated 11 beta-HSD and CCT
      activities as well as [14C]choline incorporation. We conclude, that endogenous
      glucocorticoids induce PC synthesis as well as 11 beta-HSD activity in lung and
      liver of the fetal rat. Fetal PC synthesis is not altered by increasing 11 beta
      HSD levels, because the increase of free serum corticosterone levels apparently
      exceeds the metabolising capacity of 11 beta-HSD towards term.

PMID- 8305491
TI  - Apolipoprotein-lipid association in oxidatively modified HDL and LDL.
AB  - We investigated the effect of Cu2+ catalyzed peroxidation on the status of
      tryptophan (Trp) in protein moieties in HDL and LDL together with its effect on
      apolipoprotein-lipid association. Incubation of HDL with Cu2+ resulted in a rapid
      decrease of Trp fluorescence intensity with time with a concomitant increase in
      Trp maximum emission wavelength (lambda max). LDL incubated with Cu2+ also showed
      a rapid decrease in Trp fluorescence intensity with time, with no associated
      increase in lambda max. The status of apo HDL and apo LDL was investigated after
      4 h oxidation (4h-oxHDL and 4h-oxLDL respectively). With 4h-oxHDL, the shift in
      lambda max was not associated with protein dissociation but rather with protein
      crosslinking and formation of larger HDL species. Progressive increase in lambda
      max was observed in 4h-oxHDL with increase in guanidine hydrochloride (GuHCl)
      concentration; this was not due to protein dissociation. Although oxidation of
      LDL did not produce an increase in lambda max, a significant increase in
      wavelength was observed when 4h-oxLDL was exposed to increasing concentration of
      GuHCl. SDS-polyacrylamide gel electrophoresis and nondenaturing gradient gel
      electrophoresis of the 4h-oxLDL indicated formation of smaller molecular weight
      protein fragments that were still associated with LDL. Ultracentrifugation of
      oxidized LDL in the presence and absence of GuHCl showed no dissociated protein.
      In summary, these data indicate the following: (a) lipid peroxidation has a
      direct effect on Trp residues in both HDL and LDL, (b) oxidation of HDL is
      associated with conformational change in apo HDL, crosslinking and formation of
      larger particles, (c) oxidized HDL have a more stable apolipoprotein-lipid
      association than native HDL, (d) oxidation of LDL is associated with changes in
      apo B, that by fluorescence are apparent only in presence of GuHCl and results in
      fragmentation of apo B without dissociation of protein or change in particle
      size, and (e) stability of apolipoprotein-lipid association is comparable in
      oxidized and native LDL.

PMID- 8305492
TI  - Stimulation of lipoxin synthesis from leukotriene A4 by endogenously formed 12
      hydroperoxyeicosatetraenoic acid in activated human platelets.
AB  - Human platelets are devoid of 5-lipoxygenase activity but convert exogenous
      leukotriene A4 (LTA4) either by a specific LTC4 synthase to leukotriene C4 or via
      a 12-lipoxygenase mediated reaction to lipoxins. Unstimulated platelets mainly
      produced LTC4, whereas only minor amounts of lipoxins were formed. Platelet
      activation with thrombin, collagen or ionophore A23187 increased the conversion
      of LTA4 to lipoxins and decreased the leukotriene production. Maximal effects
      were observed after incubation with ionophore A23187, which induced synthesis of
      comparable amounts of lipoxins and cysteinyl leukotrienes (LTC4, LTD4 and LTE4).
      Chelation of intra- and extracellular calcium with quin-2 and EDTA reversed the
      ionophore A23187-induced stimulation of lipoxin synthesis from LTA4 and inhibited
      the formation of 12-hydroxyeicosatetraenoic acid (12-HETE) from endogenous
      substrate. However, calcium did not affect the 12-lipoxygenase activity in the
      100,000 x g supernatant of sonicated platelet suspensions. Furthermore, the
      stimulatory effect on lipoxin formation induced by platelet agonists could be
      mimicked in intact platelets by the addition of low concentrations of arachidonic
      acid, 12-hydroperoxyeicosatetraenoic acid (12-HPETE) or 13
      hydroperoxyoctadecadienoic acid (13-HPODE). The results indicate that the
      elevated lipoxin synthesis during platelet activation is due to stimulated 12
      lipoxygenase activity induced by endogenously formed 12-HPETE.

PMID- 8305493
TI  - Tocopherols and carotenes are differently distributed in subfractions of high
      density lipoprotein.
AB  - An apolipoprotein (apo) E-rich and an apo E-poor fraction of high-density
      lipoprotein (HDL) were isolated from four healthy men by heparin-Sepharose
      affinity chromatography. On a cholesterol basis, the apo E-poor HDL fraction
      contained a third more alpha- and gamma-tocopherol and about a third less alpha-
      and beta-carotene than the apo E-rich HDL fraction. Plasma concentrations of HDL
      cholesterol were highly correlated with the contribution of the apo E-rich HDL
      subfraction to total HDL alpha-tocopherol (r = -0.990, P < 0.001).

PMID- 8305494
TI  - Structure and sequence of the Arabidopsis thaliana lipoxygenase 1 gene.
AB  - We have isolated and sequenced the Arabidopsis thaliana LOX1 gene which encodes a
      lipoxygenase. The 5255 bp sequence includes 763 bp upstream from the start codon,
      4345 bp spanning the coding region and 147 bp downstream from the stop codon. The
      coding region of the LOX1 gene consists of 8 exons separated by 7 introns. The
      introns in the LOX1 gene are located in sites predicted by the closely related
      soybean seed LOX3 gene sequence. With the exception of intron 1, the LOX1 introns
      are smaller in size than the LOX3 introns. Furthermore the Arabidopsis gene
      contains 7 introns, while the soybean gene contains 8. Four putative TATA box
      elements were identified in the 763 bp sequence upstream from the coding region,
      however only one is followed by a cap site which is located in a position
      appropriate for it to act as the initiation site for transcription.

PMID- 8305495
TI  - Carbachol stimulates Cl- secretion via activation of two distinct apical Cl-
      pathways in cultured human T84 intestinal epithelial monolayers.
AB  - The mode of action of carbachol in stimulation of transepithelial Cl- secretion
      in intact human intestinal T84 epithelial monolayers has been investigated in
      order to determine whether a DIDS-insensitive exit pathway (via CFTR) coexists
      with a DIDS-sensitive exit pathway at the apical membrane. Carbachol stimulates a
      transient inward Isc due to Cl- secretion whose magnitude is related to the basal
      level of inward Isc. The inward current responses to both carbachol and hypo
      osmotic media are abolished in nominally Ca(2+)-free media. The action of apical
      DIDS (100 microM) upon carbachol-stimulated Isc depends on the initial value of
      the basal Isc. At basal Isc levels < 10 microA cm-2, 100 microM DIDS applied to
      the apical cell border abolishes the inward Isc following exposure to both
      carbachol and hypo-osmotic media. In contrast a VIP-stimulated inward Isc is
      observed in the presence of 100 microM DIDS. After VIP stimulation of inward Isc,
      or if spontaneous basal values of Isc were > 10 microA cm-2, the carbachol
      stimulation of inward Isc was largely insensitive to 100 microM DIDS. The data
      are consistent with the participation of both DIDS-sensitive and DIDS insensitive
      pathways for Cl- at the apical membrane of human intestinal T84 epithelial cells.

PMID- 8305496
TI  - Thapsigargin-induced [Ca2+]i increase activates sodium influx in human platelets.
AB  - Using the fluorescent dyes sodium-binding-benzofuran-isophthalate and fura-2
      cytosolic free sodium concentration ([Na+]i) and cytosolic free calcium
      concentration ([Ca2+]i) were investigated in intact human platelets in order to
      characterize the effect of elevated [Ca2+]i on [Na+]i. Spectrofluorometric
      studies of [Ca2+]i and [Na+]i in intact platelets were done after specific
      inhibition of endoplasmic Ca-ATPase by thapsigargin. Thapsigargin increased
      [Ca2+]i and [Na+]i in platelets. Addition of thapsigargin increased [Na+]i from
      23.5 +/- 2.9 mM to 51.6 +/- 11.1 mM (mean +/- S.E., P < 0.05). The thapsigargin
      induced [Na+]i increase was also seen in the absence of extracellular calcium. In
      the absence of external sodium the thapsigargin induced [Na+]i increase was
      abolished, indicating that thapsigargin induced [Na+]i increase was due to sodium
      influx. Thapsigargin induced sodium influx was blocked after administration of
      NiCl2. The present results support the idea that the filling state of
      intracellular calcium stores regulate plasma permeability for sodium.

PMID- 8305497
TI  - The requirement of p47 phosphorylation for activation of NADPH oxidase by
      opsonized zymosan in human neutrophils.
AB  - Protein kinase C (PKC) inhibitors, staurosporine or 1,5-isoquinolinesulfonyl)-2
      methylpiperazine (H7), inhibited NADPH oxidase activity and phosphorylation of 47
      kDa protein (p47) in PMA-stimulated neutrophils in a dose-dependent manner. These
      PKC inhibitors, at the same doses, did not affect oxidase activity and caused
      only partial inhibition of p47 phosphorylation in OZ-stimulated neutrophils.
      There was residual (20%) phosphorylated p47 in the membranes of OZ-stimulated
      cells in the presence of PKC inhibitors, at concentrations which caused total
      inhibition of oxidase activity and p47 phosphorylation in PMA-stimulated
      neutrophils. In the presence of ionomycin, which increased intracellular calcium
      ion concentrations, staurosporine was less effective in inhibiting both
      superoxide generation and p47 phosphorylation stimulated by PMA, similar to its
      effect in OZ-stimulated cells. The results indicate that some phosphorylation of
      p47 always accompanied oxidase activation induced by PMA or OZ, though the degree
      of phosphorylation of membrane-bound p47 does not directly correlate with rates
      of superoxide production.

PMID- 8305498
TI  - Elevated NADPH-oxidase activity in neutrophils from bile-duct-ligated rats:
      changes in the kinetic parameters and in the oxidase cytosolic factor p47.
AB  - Stimulated superoxide generation was 2-fold higher in neutrophils from 20 rats
      with common bile-duct ligation (CBDL) compared to that of 20 sham-operated
      control rats. In order to study the mechanism of the higher NADPH oxidase
      activity in CBDL rats, the kinetic parameters of NADPH oxidase were analyzed. The
      Vmax of the NADPH oxidase in CBDL rat neutrophils was significantly higher than
      that of control rat neutrophils (10.2 and 5.3 nmol/min, respectively). The
      membrane and cytosol fractions of the oxidase were studied in a cell-free system.
      Neutrophil cytosol from CBDL rats added to neutrophil membranes from either CBDL
      or control rats produced 22.4 +/- 1.6 and 21.0 +/- 1.4 nmol/10(6) cells per 10
      min, respectively. When neutrophil cytosol from control rats was mixed with
      neutrophil membranes from control or CBDL rats the generation of superoxide was
      10.6 +/- 1.4 and 10.0 +/- 1.5 nmol/10(6) cells per 10 min, respectively. These
      results suggest that the cytosol components of the oxidase regulate its activity.
      By immunoblot analysis it was shown that the amount of the cytosolic factor p47
      in neutrophils of CBDL rats is higher than that present in an equal number of
      neutrophils from control rats.

PMID- 8305499
TI  - Irradiation of bovine aortic endothelial cells enhances the synthesis and
      secretion of sulphated glycosaminoglycans.
AB  - The effect of X-irradiation on the synthesis of heparan sulphate (HS) and
      chondroitin/dermatan sulphate (CS/DS) by bovine aortic endothelial cells (BAEC),
      was studied by measuring the incorporation of [35S]sulphate and [3H]glucosamine
      into newly synthesized glycosaminoglycan (GAG) chains. Medium extracts from
      irradiated cultures (5Gy) were found to contain approx. 130% more HS and 200%
      more CS/DS than unirradiated controls. Smaller increases were observed in
      cellular extracts, irradiated cultures (5Gy) containing approx. 60% more HS and
      100% more CS/DS than unirradiated controls. Structural studies showed no
      significant changes occurred upon irradiation in either the amounts or
      distribution of N- and O-sulphate groups in the HS molecule. Values for N
      sulphation of 41.1% control and 41.5% irradiated (5Gy) were obtained, the
      corresponding values for O-sulphation being 19.9% control and 20.2% irradiated.
      Isotope incorporation data indicated that sulphation of CS/DS may decrease after
      irradiation, however, analysis of chondroitin ABC lyase derived disaccharides
      showed no changes in the proportion of non-sulphated and O-sulphated
      disaccharides. The present study indicates that X-irradiation stimulates the
      synthesis and secretion of HS and CS/DS proteoglycans (PGs) by BAEC. This could
      be relevant to many features which are found to be indicative of radiation
      induced damage.

PMID- 8305501
TI  - A role for oxygen radicals in rat monocytic leukemia cell differentiation under
      stimulation with platelet-activating factor.
AB  - Combined stimulation, by superoxide ions generated by the xanthine-xanthine
      oxidase reaction, and platelet-activating factor (PAF), induced cell
      differentiation of rat monocytic leukemia cells (c-WRT-LR) to macrophage-like
      mature cells. Monitoring of cytochrome c reduction revealed that PAF stimulation
      induced the release of superoxide ions from c-WRT-LR. To further investigate the
      effect of superoxide ions in the autocrine or paracrine mechanism in cell
      differentiation, molecular species of the oxygen radicals under PAF stimulation
      were examined using the EPR spin trap, 5,5'-dimethyl-1-pyrroline N-oxide (DMPO).
      PAF and/or phorbol myristate acetate caused the formation of EPR spectra, a
      combination of DMPO/.OOH and DMPO/.OH. Since both spectra were diminished in the
      presence of superoxide dismutase, it was concluded that DMPO/.OH was derived from
      superoxide ions. Mannitol and catalase suppressed cell differentiation induced by
      combined stimulation with PAF and oxygen radicals generated by the xanthine
      xanthine oxidase reaction. Taken together, these results suggest that hydroxyl
      radicals generated by Fenton reaction from H2O2 may be involved in the mechanism
      of cell differentiation in rat monocytic leukemia cells.

PMID- 8305500
TI  - Effects of high and low pH on Ca2+i and on cell injury evoked by anoxia in
      perfused rat hepatocytes.
AB  - The effect of high and low pH on anoxic cell injury was studied in freshly
      isolated rat hepatocytes cast in agarose gel threads and perfused with Krebs
      Henseleit bicarbonate buffer (KHB) saturated with 95% O2 and 5% CO2. Cytosolic
      free calcium (Ca2+i) was measured with aequorin, intracellular pH (pHi) with
      BCECF, and lactic dehydrogenase (LDH) by the increase in NADH absorbance during
      lactate oxidation to pyruvate. A 2 h period of anoxia was induced by perfusing
      the cells with KHB saturated with 95% N2 and 5% CO2. The extracellular pH (pHo)
      was maintained at 7.4, 6.8 or 8.0 by varying the bicarbonate concentration. The
      substrate was either 5 mM glucose, 15 mM glucose or 15 mM fructose. In some
      experiments, anoxia was performed in Ca(2+)-free media by perfusing the cells
      with KHB without Ca2+ but with 0.1 mM EGTA. Reducing pHo to 6.8 during anoxia did
      not reduce the increase in Ca2+i, but but completely abolished LDH release. Under
      these conditions, pHi decreased to 6.56 +/- 0.3 when glucose was the substrate
      and to 6.18 +/- 0.25 with 15 mM fructose. Apparently, protection against anoxic
      injury caused by a low pHo is associated with a low pHi but not with a reduced
      elevation in Ca2+i. Increasing pHo to 8.0 during anoxia increased pHi above 8.0
      +/- 0.01 and doubled LDH release without significantly altering the rise in
      Ca2+i. When 15 mM fructose was present with a pHo of 8.0, pHi was still 8.0, but
      there was practically no rise in Ca2+i, and LDH release was again completely
      abolished. On the other hand, a Ca(2+)-free perfusate with a pHo of 8.0 kept the
      rise in Ca2+i below 400 nM but did not abolish the massive release of LDH caused
      by high pH. Since cell injury is caused by the activation of Ca(2+)-sensitive
      hydrolytic enzymes such as phospholipase A2, these experiments suggest that a low
      pH (< 6.5) prevents their activation even in the presence of a high Ca2+i.
      Conversely, a high pH (> 8.0) can activate hydrolytic enzymes and cause injury
      even in the absence of an elevated Ca2+i. The precise mechanism by which fructose
      protects hepatocytes against cell injury at pHi 8.0 is unclear.

PMID- 8305502
TI  - Partial purification and characterization of 'injurin-like' factor which
      stimulates production of hepatocyte growth factor.
AB  - We have previously reported the evidence for presence of a humoral factor
      'injurin', which induces expression of the hepatocyte growth factor (HGF) gene in
      MRC-5 human embryonic lung fibroblasts. We have now purified a factor from
      porcine liver which stimulates HGF production but differs from injurin. When
      injurin activity was measured as a stimulatory effect on HGF production by MRC-5
      cells, this activity was found in various acid extracts from porcine tissues,
      including liver, kidney, brain, and lung, and acid extracts from the liver was
      used for purification. When the acid extract was applied to Q-Sepharose anion
      exchange chromatography, 50-60% of the total injurin activity was absorbed to the
      column and the remaining activity was detected in the flow through fractions.
      Injurin activity was eluted from the Q-Sepharose column by NaCl concentration
      gradient with four peaks at 0.5-0.6 M, 0.7-0.8 M, 0.9-1.2 M. 1.5-2.0 M NaCl,
      thereby suggesting that the factor exists in heterogenous or various forms in
      tissues. The major active fractions were combined and applied to Mono-Q FPLC
      anion-exchange chromatography. Injurin activity eluted with a single peak at 0.9
      1.5 M NaCl and this activity was 4286 fold purified from the starting extract.
      Addition of this fraction to MRC-5 cells increased the amount of HGF pulse
      labeled with [35S]methionine to a 3-4-fold higher level than that seen in control
      cells, whereas it had no significant effect on HGF mRNA levels. Therefore, this
      factor seems to stimulate HGF synthesis affecting translational processes and is
      distinct from the previously characterized injurin which stimulates HGF gene
      expression. Chemical treatments and SDS-polyacrylamide gel electrophoresis of
      this injurin-like factor indicated that injurin-like factor is a acid- and heat
      stable non-proteinous factor with an apparent M(r) of 8-15 kDa. Since the injurin
      activity of the factor was decreased by heparinase treatment, the factor may be a
      polysulfated glycosaminoglycan related to heparin or to heparan sulfate. These
      results suggest that HGF production may be regulated by this non-proteinous
      injurin-like factor and that this factor may also play an important role in the
      regeneration of organs, through translationally enhancing HGF production.

PMID- 8305503
TI  - Participation of glycosylated residues in the human sperm acrosome reaction:
      possible role of N-acetylglucosaminidase.
AB  - Sperm binding to the egg zona pellucida is mediated by complementary protein
      carbohydrate interaction. This binding results in the exocytosis of the sperm
      acrosome, or acrosome reaction (AR). We report the effect of different
      neoglycoproteins (sugar residues covalently bound to bovine serum albumin) on the
      human sperm AR. p-Aminophenyl-N-acetyl-beta-D-glucosaminide-BSA (BSA-GlcNAc) and
      p-aminophenyl-alpha-D-mannopyranoside-BSA (BSA-Man) at 1 micrograms/ml were
      capable of inducing the greatest percentages of AR (3-fold stimulation with
      respect to controls), while other NeoGPs had only a weak effect on this process.
      The BSA-GlcNAc-induced acrosome reaction was inhibited by N-acetylglucosamine
      (GlcNAc), p-nitrophenyl-GlcNAc, and purified soluble beta-N-acetylglucosaminidase
      (beta NAG). The induction of the AR with BSA-Man could be inhibited by mannose,
      while soluble alpha-mannosidase was only partially effective. These data suggest
      that binding sites for GlcNAc and mannose may be involved in the induction of the
      AR in human sperm. The characteristics of the BSA-GlcNAc induction suggest that
      the beta NAG molecule may be the mediator of this effect.

PMID- 8305504
TI  - K+ ionophores inhibit nerve growth factor-induced neuronal differentiation in rat
      adrenal pheochromocytoma PC12 cells.
AB  - Incubation with a K+/H+ ionophore nigericin attenuated the nerve growth factor
      (NGF)-induced neurite outgrowth in rat pheochromocytoma PC12 cells. However, a
      Na+/H+ ionophore monensin and a Ca2+ ionophore A23187 did not inhibited the
      neurite outgrowth. Nigericin also inhibited the NGF-caused induction of
      acetylcholinesterase and suppression of cell proliferation. These changes were
      dependent on the amount of the ionophore added to the culture. In addition, a
      distinct K+ ionophore, valinomycin, similarly inhibited the NGF-induced neuronal
      differentiation. These results suggest the presence of the K+ ionophore-sensitive
      mechanism in the NGF-induced differentiation system in PC12 cells.

PMID- 8305505
TI  - Lipocortin I is not accessible for protein kinase C bound to the cytoplasmic
      surface of the plasma membrane in streptolysin-O-permeabilized pig granulocytes.
AB  - We previously observed a 38 kDa protein that was a major protein component of the
      cytosolic extract of pig granulocytes and the dominant substrate of protein
      kinase C at supra-physiological Ca2+ concentrations. The purified 38 kDa protein
      itself required Ca2+ to be phosphorylated by protein kinase C. Now we demonstrate
      that this protein, which is also present in human granulocytes, is identical to
      lipocortin I. The identification is based on the chromatographic properties and
      immunoblot of the purified protein which is also a good substrate for tissue
      transglutaminase. Phosphorylation of lipocortin I by protein kinase C was
      investigated in granulocytes permeabilized with streptolysin-O. At physiological
      intracellular Ca2+ concentrations lipocortin I was not phosphorylated at all. At
      supra-physiological Ca2+ concentrations (0.5 mM), lipocortin I was also not
      phosphorylated when protein kinase C was translocated to the membrane by
      treatment of the cells with phorbol myristate acetate. Its phosphorylation was
      detectable only in control experiments when protein kinase C was activated in the
      cytosol by the addition of dioleoylglycerol and phosphatidylserine to the
      permeabilized cells. The data presented show that, in permeabilized granulocytes,
      Ca(2+)-lipocortin is not formed at physiological Ca2+ concentrations, and at
      supra-physiological Ca2+ concentrations the Ca(2+)-lipocortin I is not accessible
      to protein kinase C bound to the cytoplasmic surface of the plasma membrane.

PMID- 8305506
TI  - Formation of endogenous free sphingoid bases in cells induced by changing medium
      conditions.
AB  - Sphingoid bases are precursors and breakdown products of sphingolipids and may
      function as second messengers. Here we have tested the hypothesis that sphingoid
      bases are produced in cells in response to external stimuli. Using a high
      performance liquid chromatography system, the pattern and the amounts of free
      sphingoid bases in various cell types (i.e., NIH-3T3, A431, NG108-15) were
      determined. The predominant sphingoid base in these mammalian cells was
      identified as C-18 sphingosine, followed by C-18 sphinganine
      (dihydrosphingosine). In all cells examined, the levels of endogenous sphingoid
      bases can be rapidly elevated by replacing cell-conditioned medium with Hepes
      buffered saline or with fresh medium, causing a dramatic increase (up to 9.5
      fold) in sphingosine levels within 60 min; sphinganine levels were raised to a
      lesser extent (up to 4.5-fold). Addition of ammonium ions inhibited the
      generation of sphingoid bases. These results suggest that the machinery for
      metabolizing sphingoid bases can be stimulated rapidly, although the exact nature
      of the stimulus remains obscure. Nevertheless, the ability to control sphingosine
      formation in cells by changing medium conditions provides a powerful tool for
      investigations of the physiological roles of endogenous sphingosine.

PMID- 8305508
TI  - Sequence of the 3'-noncoding region of the luteinizing hormone receptor gene and
      identification of two polyadenylation domains that generate the major mRNA forms.
AB  - We present 6.2 kb of the 3'-noncoding region sequence of the rat luteinizing
      hormone receptor (LHR) gene and identification of two functional polyadenylation
      (pA) domains, H1 (nt 2368-2491) and H2 (nt 5579-5768) responsible for 3'-end
      processing of the 2.6/2.3 kb and the 5.8 kb LHR mRNA, respectively. Two identical
      copies of pA elements AAUAUA in H1 and of AAUAAA in H2 account for micro
      heterogeneous poly(A) addition at each of the two pA regions. Both LH
      holoreceptor and major splice variant form B (lacking the first 266 bp of exon
      11) are identified in H1-terminated (2.6 kb and 2.3 kb) and H2-terminated (5.8
      kb) mRNA transcripts. A rodent repetitive DNA LINE R domain 3' of H1 within the
      major 5.8 kb species and a B2 element downstream of H2 were identified. Alignment
      of the 3'-noncoding region of LHR with TSH, FSH and beta 2-adrenergic receptors
      indicate that H1 pA signal is unique to the LHR and may represent an insertion
      domain.

PMID- 8305507
TI  - cDNA cloning and sequence analysis of the bovine adrenocorticotropic hormone
      (ACTH) receptor.
AB  - We isolated five independent cDNAs of nearly 3000 bp for the bovine ACTH receptor
      by screening adrenal cortex cDNA libraries with a PCR cloned cDNA fragment. The
      deduced receptor sequence includes 297 residues (M(r) = 33,258) with 81% identity
      with the human ACTH receptor, and shows seven hydrophobic transmembrane domains.
      The calculated M(r) of the receptor is smaller than the 40-45 kDa observed in
      crosslinking studies with labeled ACTH. Since the bovine and human receptors have
      two glycosylation motifs in the N-terminus, the difference may result from
      glycosylation of the receptor. Analysis of the sequences of both bovine and human
      receptors revealed a single protein kinase. A phosphorylation motif located in
      the third intracellular loop (Ser-209) juxtaposed to a protein kinase C
      phosphorylation motif (Thr-204). Thus, the involvement of protein kinase A and C
      pathways in ACTH action may be mediated in part by phosphorylation of the ACTH
      receptor at these motifs. The 3'-untranslated region of the bovine cDNA is > 2000
      bp and includes two inverse repeats giving an extensive and strong secondary
      structure to the ACTH receptor RNA.

PMID- 8305509
TI  - Nucleic acid-incorporated azidonucleotides: probes for studying the interaction
      of RNA or DNA with proteins and other nucleic acids.

PMID- 8305510
TI  - Synthesis of cobalt carbonyl complexes of cortisol and testosterone. Study of
      their recognition by specific polyclonal antibodies.
AB  - We have synthesized organometallic complexes of steroids (cortisol, testosterone,
      dihydrotestosterone) for potential use as tracers in nonisotopic carbonyl-metal
      immunoassays (CMIA). An ethynyl/CO2(CO)6 fragment at the end of a five-atom
      spacer was coupled to position 3 of the steroid skeleton. In the case of
      cortisol, we exploited the difference in reactivity of the ketone and enone
      functions toward amines in order to form an enamine which was then made to react
      with carboxymethylamine to yield 3-[(carboxymethyl)oxime] steroid. Activation of
      the carboxylic acid function with N,N'-dicyclohexylcarbodiimide in the presence
      of propargylamine introduced an acetylenic function at the end of the spacer. The
      triple bond was then complexed by CO2(CO)8 to form complexes 5a-c. Complexes for
      use in CMIA should be stable in biologic media and effectively recognize specific
      antibodies. Complexes 5a-c were stable in the buffers we use in biochemical
      tests. Their cross reactivities for anti-cortisol and anti-testosterone
      antibodies ranged from 50 to 110% according to batch, indicating, first, that the
      addition of an organometallic complex in position 3 of the steroid skeleton does
      not hinder recognition between the organometallic steroid and antibody and,
      second, that their individual behavior differs substantially according to
      antibody batch. Although all of these complexes could be used as tracers in CMIA,
      it is necessary, in each case, to establish which tracer-antibody duo gives rise
      to the most sensitive immunoassay.

PMID- 8305511
TI  - Labeling of proteins by organometallic complexes of rhenium. (I). Synthesis and
      biological activity of the conjugates.
AB  - We describe herein a totally new pathway for the introduction of rhenium in the
      form of low oxidation state organometallic complexes covalently attached to
      various proteins. The synthesis of several rhenium conjugates takes advantage of
      the specificity of N-succinimidyl esters for amino residues. Conjugation
      experiments were carried out under various conditions, and analysis of the
      conjugates was performed by FT-IR spectroscopy. Yields were optimized and reached
      50%. Furthermore, the conjugate resulting from the coupling of N-succinimidyl 4
      [eta 5-cyclopentadienylrhenium tricarbonyl] 4-oxobutanoate to an anti-hTSH
      monoclonal antibody retained a satisfactory immunoreactivity. Finally, IR
      detection of conjugates adsorbed onto nitrocellulose membranes was achieved and
      response was found to be related to the coupling extent of the conjugate.

PMID- 8305512
TI  - Synthesis of bulky beta-lactams for inhibition of cell surface beta-lactamase
      activity.
AB  - Procedures are described for the preparation of a series of compounds consisting
      of methicillin linked to beta-cyclodextrin through variable hydrophilic linkers.
      beta-Cyclodextrin was coupled to the antibiotic methicillin to prevent the
      antibiotic from permeating the outer membranes of bacteria. Stoichiometric
      oxidation of the beta-cyclodextrin with sodium metaperiodate provided a
      functional group for coupling to the linker. Methicillin was coupled to the
      linker via its carboxyl group. These compounds were tested for activity toward
      purified beta-lactamase. The length of the spacer arm between beta-cyclodextrin
      and methicillin was crucial in binding beta-lactamase and inhibiting activity.
      Compounds with longer spacers were effective inhibitors of beta-lactamase. We
      have deduced that the length of the spacer should be greater than 16 A for
      optimum inhibition of beta-lactamase.

PMID- 8305513
TI  - Biologically active interleukin 2-ricin A chain fusion proteins may require
      intracellular proteolytic cleavage to exhibit a cytotoxic effect.
AB  - DNA fusions encoding chimeric proteins in which human interleukin 2 (IL2) was
      fused to the A subunit of the plant cytotoxin ricin (RA) have been expressed in
      Xenopus oocytes. The constructs contained N-terminal IL2 and C-terminal RA, or N
      terminal RA and C-terminal IL2. In the expressed chimeric proteins, the IL2 and
      RA moieties were joined by a peptide sequence containing a proteolytic cleavage
      site. Two proteolytically-sensitive peptide sequences were utilized; a peptide
      that forms the trypsin-sensitive disulfide-bonded loop in diphtheria toxin (DT)
      or a synthetic peptide containing the factor Xa recognition site in a sequence
      flanked by two cysteine residues. In an in vitro cell free system the RA
      component was biologically active in all chimeric proteins produced since it
      specifically depurinated 28S ribosomal RNA. Proteolytic cleavage of the chimeras
      with either trypsin or factor Xa as appropriate separated the IL2 and RA
      moieties, but they did not remain covalently linked by a disulfide bond. Because
      of this, the cytotoxicity of protease-treated chimeras could not be assessed.
      Chimeras not pretreated with factor Xa but which contained the factor Xa target
      sequence were not cytotoxic to CTLL-2 cells. Rather, these molecules had a
      stimulatory effect that was ascribed to the IL2 moiety. In contrast, recombinant
      chimeric toxins containing the DT loop sequence were cytotoxic to CTLL-2 cells.
      Taken together the data suggest that RA-containing chimeras require intracellular
      proteolytic cleavage to release the RA moiety to render them cytotoxic to target
      cells.

PMID- 8305514
TI  - Efficient transformation of mammalian cells using DNA interpolyelectrolyte
      complexes with carbon chain polycations.
AB  - A new method for mammalian cell transformation is proposed which is based on
      incorporation of plasmids into interpolyelectrolyte complexes (IPECs) with carbon
      chain polycations. The method is illustrated by examples of pRSV CAT and p beta
      Gal plasmid IPECs with poly(N-ethyl-4-vinylpyridinium bromide) (C2PVP) and poly(N
      ethyl-4-vinylpyridinium)-poly(N-cetyl-4-vinylpyridinium+ ++) bromides random
      copolymer (C16PVP). These IPECs are produced spontaneously due to formation of a
      cooperative system of interchain electrostatic bonds after mixing DNA and
      polycation solutions. The interaction of IPEC with normal mouse fibroblasts NIH
      3T3, human T-lymphoma "Jurkat", and Mardin Darby canine kidney cells has been
      studied. The data obtained has revealed that plasmid incorporation into IPECs
      significantly enhances both DNA adsorption on the plasma membrane and DNA uptake
      into a cell. The in vitro transformation of NIH 3T3 cells was monitored by a
      standard cloramphenicol acetyltransferase (CAT) assay (pRSV CAT plasmid) and by
      detection of beta-galactosidase (beta-Gal) expression using 4-methylumbeliferril
      beta-D-galactopyranoside as a substrate (p beta-Gal plasmid). In both cases it
      has been proved that IPEC-incorporated plasmids possess an ability for efficient
      cell transformation. The transforming activity of IPECs depends on their
      composition and polycation chemical structure. Under optimal conditions the
      efficiency of cell transformation with IPECs is several fold higher than that
      observed during standard calcium phosphate precipitation. The mechanism of the
      phenomenon observed is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305515
TI  - Preparation and characterization of conjugates of monoclonal antibodies and
      staphylococcal enterotoxin A using a new hydrophilic cross-linker.
AB  - Conjugates between monoclonal antibodies recognizing human cancer cells and the
      superantigen staphylococcal enterotoxin A (mAb-SEA) represent a potential novel
      approach to tumor therapy. Such mAb-SEA conjugates direct T-cells to lyse colon
      carcinoma cells in vitro. The synthesis of mAb-SEA conjugates which were prepared
      by introducing thiol groups on SEA and iodoacetyl or maleimide groups on mAb
      forming a stable thioether linkage between SEA and mAb is described. A
      hydrophilic spacer, composed of repeated ethylene oxide units, was constructed to
      increase the distance between SEA and mAb, preserving biological activity of both
      proteins. The degree of modification of mAb with SEA was determined with SDS
      PAGE. Variables influencing the composition of the conjugates and their effect on
      the tumor-cell cytotoxicity were studied and optimal conditions for the synthesis
      were established. Functionally active mAb-SEA conjugates were prepared from a
      panel of different mAb and T-cell-dependent cytotoxicity against several human
      cancer types including colon, ovarial, breast, and renal cancer was obtained.
      This suggests that mAb-SEA conjugates may be of value in the treatment of human
      neoplastic disease.

PMID- 8305516
TI  - 2',5'-Oligoadenylate:antisense chimeras--synthesis and properties.
AB  - We have synthesized a novel bioconjugate which joins an antisense oligonucleotide
      to a unique and potent inhibitor of translation,pn5'A2'(p5'A2')mp5'A(2-5A). Two
      residues of 4-hydroxybutyl phosphate were employed as linkers to attach the 2',5'
      oligoadenylate moiety through its 2'-terminus to the 5'-terminus of the chosen
      antisense sequence, (dT)20. The syntheses were carried on a solid support
      according to the phosphite triester method of DNA synthesis (Letsinger, R.L.,
      Lunsford, W.B. (1976) J. Am. Chem. Soc. 98, 3655-3661; Beaucage, S.L., and
      Caruthers, M.H. (1981) Tetrahedron Lett. 22, 1859-1862). The generated 2-5A
      antisense chimeras retained both the ability of the 2-5A molecule to activate the
      2-5A-dependent RNase as well as the ability of the oligo(dT) moiety to hybridize
      to the complementary poly(A). Moreover, the chimera, when annealed to its target
      nucleic acid sequence, was still effectively bound to the 2-5A-dependent
      nuclease. The methodology described represents a new approach to the selective
      modulation of mRNA expression.

PMID- 8305517
TI  - Comparison of the cytotoxic effect of hormonotoxins prepared with the use of
      heterobifunctional cross-linking agents N-succinimidyl 3-(2
      pyridyldithio)propionate and N-succinimidyl 6-[3-(2
      pyridyldithio)propionamido]hexanoate.
AB  - With the aim of developing cytotoxic hybrid molecules which can be selectively
      targeted to specific cells in the gonads, a single chain ribosome-inactivating
      protein, gelonin, was conjugated to ovine luteinizing hormone (oLH) with the use
      of heterobifunctional cross-linking agents N-succinimidyl3-(2-pyridyldithio)
      propionate (SPDP) and long-chain SPDP. Four hormonotoxins were synthesized having
      a variable spacer arm between oLH and gelonin. The spacer arms in C200A, C210A,
      C220A, and C230A were 13.6, 22.4, 22.4, and 31.2 A long, respectively. Extensive
      physiochemical and biochemical analysis revealed a 1:1 molar ratio of the
      ingredients in its oLH-S-S-gelonin conjugates. The linkage occurred through the
      epsilon-NH2 group of the alpha-subunit of oLH as judged from RP-HPLC analysis.
      The hormonotoxins retained substantial receptor binding ability, steriodogenic
      activity, and immunoreactivity of oLH and gelonin to their respective antibodies.
      Hormonotoxins bind to Leydig tumor cells via oLH, leaving gelonin free as judged
      by competitive displacement analysis. The hormonotoxins internalized to a
      sufficient degree to effectively inhibit protein synthesis. Upon comparison,
      immunoreactivity, receptor binding steroidogenic activity, and cytotoxicity of
      oLH-S-S-gelonin conjugates prepared with the use of only LC-SPDP (C230A, 31.2-A
      spacer arm) and by using both SPDP and LC-SPDP (C210A and C220A, 22.4-A spacer
      arm) were found to be comparable with that of conjugate prepared with SPDP alone
      (C200A, 13.6-A spacer arm). Therefore, it may be concluded that the cytotoxicity
      of oLH-based hormonotoxin remained unaffected with the use of long-chain spacer
      arms which are believed to be used generally to avoid steric hindrance.

PMID- 8305518
TI  - Conjugation of Cu,Zn-superoxide dismutase with succinylated gelatin:
      pharmacological activity and cell-lubricating function.
AB  - Superoxide dismutase (SOD) and succinylated gelatin (succinyl gelatin) were
      conjugated to improve in vivo pharmacological activity of SOD. Lysyl residues of
      human recombinant Cu,Zn-SOD were cross-linked with carboxyl residues of succinyl
      gelatin using 1-ethyl-3-[3- (dimethylamino)propyl]carbodiimide. Various chemical
      and pharmacokinetic parameters of the conjugate were determined. Analysis by
      atomic absorption spectrometry and amino acid composition revealed that the
      conjugate was composed of about 2.9 mol of succinyl gelatin (with a mean
      molecular weight of 23,000) to 1 mol of SOD and exhibited an apparent mean
      molecular weight of 98,000. The conjugate retained almost 100% of its original
      activity on a molar basis. When the succinyl gelatin-conjugated Cu,Zn-SOD (Suc
      gel-SOD) was administered intravenously to mice, its plasma half-life was
      prolonged to 29.7 min compared with 4.5 min for native SOD. Tissue distribution
      analysis revealed that intravenously administered Suc-gel-SOD showed a much
      greater accumulation than native SOD in the liver followed by in decreasing order
      the kidney, the lung, and the spleen; native SOD was excreted more rapidly into
      urine before it accumulated in tissues. Furthermore, Suc-gel-SOD exhibited lower
      antigenicity and immunogenicity than native SOD, and it had a better therapeutic
      effect against ischemic edema of the foot pad in mice. The conjugate was found to
      accumulate more than native SOD in the ischemic foot pad. A newly added property
      of the conjugate is cell-lubricating activity, which facilitated cell passage
      through micropores and reduced hemolysis during cell passage in vitro.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8305519
TI  - Nucleosides and nucleotides. 121. Synthesis of oligonucleotides carrying linker
      groups at the 1'-position of sugar residues.
AB  - Novel 2'-deoxyuridine analogues carrying aminoalkyl linkers at the 1'-position of
      the sugar residues were synthesized and incorporated into oligonucleotides, then
      intercalating groups such as an anthraquinone derivative and a pyrene derivative
      were attached to the amino groups. Duplexes consisting of the oligonucleotides
      carrying the linker groups and a complementary ribonucleotide were more stable
      than an unmodified parent duplex, but the duplexes consisting of the
      oligonucleotides and a complementary deoxyribonucleotide were less stable. The
      oligonucleotides carrying the linker groups were more resistant to nuclease P1
      and venom phosphodiesterase than an unmodified oligonucleotide. Furthermore, a
      duplex formed by the oligonucleotide analogue and the complementary
      ribonucleotide was a substrate for ribonuclease H.

PMID- 8305520
TI  - Preparation and properties of thermoreversible, phase-separating enzyme-oligo(N
      isopropylacrylamide) conjugates.
AB  - A thermoreversible N-isopropylacrylamide (NIPAAm) oligomer with an N
      hydroxysuccinimide (NHS) ester functional end group has been prepared for
      coupling to an enzyme, beta-D-glucosidase, to form a thermoreversible, phase
      separating polymer-enzyme conjugate. This conjugate can be used for separation,
      recovery, and recycle of an enzyme simply by applying small temperature changes
      to the reaction medium. In contrast to the random polymer-enzyme conjugates
      previously reported by us and others in the literature, in this study the
      conjugate is formed by a single, end attachment of each oligomer chain to the
      enzyme. Preliminary studies show that the conjugated enzyme exhibits very high
      retention of activity, even higher than native enzyme, and shows improved thermal
      stability compared to native enzyme.

PMID- 8305521
TI  - Protein conjugates of defined structure: synthesis and use of a new carrier
      molecule.
AB  - A new carrier molecule, NH2OCH2CO-(Gly)3-[Lys(H-Ser-)]5-Gly-OH, has been
      synthesized to facilitate the preparation of protein conjugates of defined
      structure. Special features are as follows: (i) (aminooxy)-acetyl as a terminal
      group, which reacts specifically to form an oxime bond under very mild conditions
      with an aldehyde group placed on a protein in a prior step; (ii) a spacer group
      of three Gly residues; and (iii) a set of five Lys residues, each of which is
      acylated with a Ser residue. A second form of the carrier molecule, HCO-m-C6H4CH
      = NOCH2CO-(Gly)3-[Lys(H-Ser)]5-Gly-OH, was also prepared. This form possesses a
      terminal aldehyde group which permits site-specific attachment by formation of a
      hydrazone bond to the carboxyl termini of polypeptide chains which have been
      modified enzymatically with carbohydrazide in a prior step. Once the carrier is
      linked to protein in one of the above ways, i.e. through formation of either an
      oxime or hydrazone bond, the Ser residues of the carrier (but not of the protein)
      may be oxidized by very mild periodate treatment to generate aldehyde groups.
      Drugs possessing a hydrazide group (e.g. methotrexate gamma-hydrazide or
      desacetylvincaleukoblastine hydrazide) may then be conjugated via hydrazone
      formation to the aldehyde groups of the carrier. A cluster of five drug molecules
      may thus be attached to a single site on a protein, giving a relatively
      homogeneous product in spite of the high drug conjugation ratio. Synthesis of the
      carrier, formation of a pentadrug-protein conjugate, and wider implications of
      the chemistry are presented.

PMID- 8305522
TI  - Site-directed double fluorescent tagging of human renin and collagenase (MMP-1)
      substrate peptides using the periodate oxidation of N-terminal serine. An
      apparently general strategy for provision of energy-transfer substrates for
      proteases.
AB  - Periodate in neutral aqueous solution rapidly converts N-terminal Ser or Thr to
      an alpha-N-glyoxylyl moiety that can serve as the locus for incorporation of a
      modifying group [Geoghegan, K. F., and Stroh, J. G. (1992) Bioconjugate Chem. 3,
      138-146. Gaertner, H. F. et al. (1992) Bioconjugate Chem. 3, 262-268]. The
      usefulness of this procedure has been further illuminated in a route to "energy
      transfer" substrates for endoproteases. Each such substrate is an oligopeptide
      cleavable by a proteinase, but modified (usually at its termini) with two
      chromophores that form an energy donor-acceptor pair. Production of these
      substrates is an exercise in double site-directed peptide modification. The new
      route is composed of three steps, beginning from an unprotected peptide in which
      a sequence recognized by the pertinent enzyme is placed between N-terminal Ser
      and C-terminal Lys. Lys may not occur elsewhere in the peptide. Periodate
      oxidation converts the N-terminal Ser to an alpha-N-glyoxylyl group, which is
      then allowed to form a hydrazone with the carbohydrazide derivative Lucifer
      Yellow CH, a hydrophilic fluor with a large Stokes shift (excitation maximum, 425
      nm; emission maximum, 525 nm). Finally, the modified peptide is allowed to react
      with 5-carboxytetramethylrhodamine succinimidyl ester. This reaction selectively
      modifies the epsilon-amino group of C-terminal Lys, the only amino group
      remaining in the peptide. 5-Carboxytetramethylrhodamine strongly (> 90%) quenches
      Lucifer Yellow fluorescence by resonance energy transfer in the intact substrate,
      but enzyme-catalyzed cleavage eliminates the quenching. The resulting increase in
      fluorescence may be used to follow the hydrolytic reaction.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8305523
TI  - Chlorinated phenyl azides as photolabeling reagents. Synthesis of an ortho,ortho'
      dichlorinated arylazido PCP receptor ligand.
AB  - The enhanced photolabeling properties of chlorinated phenyl azides are
      demonstrated by the synthesis and photolysis of methyl 4-azido-2,3,5,6
      tetrachlorobenzoate (3) and methyl 4-azido-3,5-dichlorobenzoate (4). Photolysis
      of azide 3 in 1 M diethylamine/cyclohexane as the trapping medium gave 34% NH
      insertion product. Similar photolysis of azide 4 gave 35% NH insertion product.
      These results demonstrate that chlorinated phenyl azides are significantly better
      at undergoing NH insertion than nonhalogenated analogs and suggest that
      improvement of existing aryl azide-based photolabels might be achieved by
      introduction of chlorine atoms on either side of the azide group. As an
      application, 3-azido-2,4-dichloro-10,5-(iminomethano)-10,11-dihydro-5H-
      dibenzo[a,d]cycloheptene (19), an analog of the potent PCP receptor ligand IDDC
      (14), was synthesized and its affinity for the PCP receptor was determined to be
      6.3 +/- 0.7 microM (IC50 against [3H]MK801).

PMID- 8305524
TI  - Synthesis and ribosome binding properties of model mRNAs modified with undecagold
      cluster.
AB  - The synthesis and purification of short model messenger RNAs modified with
      undecagold cluster are described. A monoamino undecagold cluster was introduced
      on the oxidized 3' cis-glycol group of the mRNA followed by reduction of the
      formed Schiff's base. The stability of the modified mRNA under the conditions
      used for in vitro messenger RNA translation is studied. The possibility of the
      formation of a specific translational initiation complex with bacterial ribosomes
      and modified mRNAs is shown. The results of these experiments indicate that the
      attachment of an undecagold cluster to a mRNA is a useful tool for electron
      microscopic and crystallographic studies.

PMID- 8305525
TI  - Chemical modification of silk fibroin with cyanuric chloride-activated
      poly(ethylene glycol): analyses of reaction site by 1H-NMR spectroscopy and
      conformation of the conjugates.
AB  - Solubilized silk fibroin (SF) in 0.1 M borate buffer (pH 9.4) was modified with 2
      O-[methoxy(polyethylene glycol)]-4,6-dichloro-s-triazine (actPEG1) at 4 degrees
      C. The weight of the modified SF (PEG1-SF) was at least 3.2 times that of the
      starting material SF. Amino acid analysis of PEG1-SF suggested that the
      nucleophilic epsilon-amino group of the lysine residue and the nucleophilic
      imidazole group of the histidine residue in SF reacted with actPEG1. The 1H-NMR
      spectrum of PEG1-SF showed a downfield shift of the aromatic protons of the
      tyrosine residue from the corresponding protons of SF. The 1H-NMR spectrum of the
      SF reacted with cyanuric fluoride (CyF), whose fluorine atoms are known to react
      with the phenolic hydroxyl group of the tyrosine residue, also showed the
      downfield shift. These results suggested that the reaction site of SF with
      actPEG1 was the phenolic hydroxyl group of the tyrosine residue in addition to
      the lysine and histidine residues. The conformation of PEG1-SF in a solid state
      was examined by means of IR and X-ray measurement. The IR spectrum of PEG1-SF
      revealed a change in secondary structure from random coil to beta-sheet due to
      the coexistence of PEG molecules. The X-ray diffraction pattern of PEG1-SF
      indicated that the PEG molecules covalently bonding to SF narrowed the spacing of
      the interchain periodicity and promoted the formation of the interchain beta
      sheet.

PMID- 8305527
TI  - A simplified method for the preparation of succinimidyl carbonate polyethylene
      glycol for coupling to proteins.
AB  - An improved method for the activation of polyethylene glycol with commercially
      available succinimidyl carbonate is described. The activated polyethylene glycol
      was coupled to proteins in high yield.

PMID- 8305526
TI  - Biotinylated isocoumarins, new inhibitors and reagents for detection,
      localization, and isolation of serine proteases.
AB  - Eight new biotinylated, mechanism-based isocoumarin serine protease inhibitors
      have been designed and synthesized to detect, localize, and isolate serine
      proteases. Isocoumarins that contain a 4-chloro group, a biotinylated substituent
      at the 7-position, and different 3-alkoxy groups are inhibitors of various serine
      proteases including human leukocyte elastase (HLE), porcine pancreatic elastase
      (PPE), trypsin, human recombinant granzyme A, chymotrypsin, and cathepsin G.
      Insertion of spacers between the isocoumarin moiety and the biotin moiety
      enhanced enzyme inhibitory potency and may also promote binding of the enzyme
      inhibitor complex to avidin. The 3-alkoxy groups conferred selectivity toward
      different serine proteases with chymotrypsin being inhibited effectively by
      compounds with 3-phenylethoxy groups while derivatives with 3-methoxy, ethoxy, or
      propoxy groups were potent inhibitors of HLE and moderate inhibitors of PPE. Full
      enzymatic activity was regained after the immediate addition of hydroxylamine to
      the inactivated chymotrypsin and PPE derivatives, which indicated that a simple
      acyl enzyme derivative is formed initially in the inhibition reaction. Egg avidin
      did not effect the rate of spontaneous enzyme reactivation rate while
      streptavidin accelerated the reactivation reaction. PPE inhibited by 7-[[6
      (biotinylamino)caproyl]amino]-4-chloro-3- ethoxyisocoumarin (BIC 5) or 7-[[6-[[6
      (biotinylamino)caproyl]amino] caproyl]amino]-4-chloro-3-methoxyisocoumarin (BIC
      7) was bound to immobilized avidin columns. Most of inhibited PPE could be eluted
      from the monomeric or tetrameric avidin columns but only a portion (40-70%) of
      the enzyme was active due to the partial formation of a stable alkylated enzyme
      derivative during the isolation process.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305528
TI  - Preparation of sulfhydrylborane-dextran conjugates for boron neutron capture
      therapy.
AB  - This study presents a carrier system for boron, potentially useful in boron
      neutron capture therapy (BNCT). Na2B12H11SH (BSH) was covalently coupled to
      dextran derivatives. This was accomplished in two ways. The first method
      comprises activation of dextran with 1-cyano-4-(dimethylamino)pyridine (CDAP)
      with subsequent coupling of 2-aminoethyl pyridyl disulfide (method A). The
      thiolated dextran could then couple BSH in a disulfide exchange reaction. In the
      second procedure, dextran was derivatized to a multially derivative (method B)
      which reacted with BSH in a free-radical-initiated addition reaction. The
      assessment of boron content of the conjugates was done by elemental analysis of
      sulfur and atomic spectroscopy of boron (ICP-AES). With method A, only limited
      numbers of boron cages could be coupled (10-20 cages per dextran chain). With
      method B, 100-125 boron cages per dextran chain was obtained, corresponding to
      1200-1500 boron atoms per dextran chain. This result makes this derivative a
      promising template for use in the development of BNCT agents.

PMID- 8305529
TI  - Synthesis and radioiodination of N-Boc-p-(tri-n-butylstannyl)-L-phenylalanine
      tetrafluorophenyl ester: preparation of a radiolabeled phenylalanine derivative
      for peptide synthesis.
AB  - An investigation to prepare a phenylalanine derivative which could be
      radioiodinated and used directly in peptide synthesis was conducted. N-Boc-p-(tri
      n-butylstannyl)-L-phenylalanine tetrafluorophenyl ester was targeted and
      synthesized from N-Boc-p-iodo-L-phenylalanine. The requisite aryl stannylation
      reaction was found to be best conducted using the phenylalanine methyl ester.
      Thus, N-Boc-p-iodo-L-phenylalanine methyl ester was prepared and stannylated
      using bis(tributyltin) and tetrakis-(triphenylphosphine)palladium(0) in refluxing
      toluene to prepare N-Boc-p-(tri-n-butylstannyl)-L-phenylalanine methyl ester.
      Demethylation with aqueous base was accomplished without racemization to yield N
      Boc-p-(tri-n-butylstannyl)-L-phenylalanine. Preparation of the targeted
      stannylphenylalanine tetrafluorophenyl ester was then accomplished using 2,3,5,6
      tetrafluorophenol and 1,3-dicyclohexyl-carbodiimide in anhydrous THF. Iodination
      and radioiodination reactions of the targeted compound were conducted in MeOH/1%
      HOAc to yield 83-95% of the desired N-Boc-p-[*I]iodo-L-phenylalanine
      tetrafluorophenyl ester.

PMID- 8305530
TI  - Purification and characterization of IL6-PE4E, a recombinant fusion of
      interleukin 6 with Pseudomonas exotoxin.
AB  - We have developed a procedure to purify the recombinant fusion toxin IL6-PE4E
      from Escherichia coli which results in a high yield of fully active monomeric
      protein of high purity and very low endotoxin content. The chimeric toxin is
      composed of human interleukin 6 (IL6) fused to a derivative of Pseudomonas
      exotoxin (PE) containing mutations in the binding domain which prevent binding to
      the PE receptor. In a typical preparation, 20 g of E. coli cells expressing the
      plasmid encoding IL6-PE4E were treated with lysozyme and washed repeatedly with
      detergent (Triton X-100), to obtain 500 mg of inclusion bodies. The recombinant
      protein was denatured and reduced in guanidine hydrochloride solution containing
      dithioerythritol and refolded in a redox buffer containing oxidized glutathione
      and L-arginine. After purification of the dialyzed protein by anion-exchange,
      polymyxin B, and sizing chromatography, we obtained 100 mg (20% of recombinant
      protein) of purified monomer with 0.6-2.5 endotoxin units/mg of protein. Amino
      terminal sequencing confirmed the first 20 amino acids. IL6-PE4E purified in this
      manner was fully cytotoxic toward human multiple myeloma, hepatoma, epidermoid
      carcinoma, and prostate carcinoma cell lines. After intravenous injection into
      mice, we found the dose-limiting toxicity to be to the liver, by measurement of
      serum transaminases and histologic evaluation of the liver. The LD50 was 450
      micrograms/kg. We conclude that IL6-PE4E can be purified efficiently for
      preclinical testing.

PMID- 8305531
TI  - Therapeutic modalities.

PMID- 8305532
TI  - High-dose rate brachytherapy for carcinoma of the cervix.
AB  - Increasingly popular in Europe and Asia as the intracavitary component for
      cervical cancer radiotherapy, high-dose rate brachytherapy demonstrates certain
      advantages over historical low-dose rate treatments. High-dose rate intracavitary
      treatment improves radiation safety, lessens treatment times, allows for
      outpatient treatment regimens, and has improved packing and retraction
      techniques, which can decrease rectal and bladder doses. Although retrospective
      studies of high-dose rate treatment show survival rates comparable with those of
      historical low-dose rate intracavitary treatment, there have been few randomized,
      prospective studies to support the use of high-dose rate techniques. Low- and
      high-dose rate comparisons are further complicated by the lack of standardized
      fractionation schemes and dose prescriptions for high-dose rate treatment. Recent
      data showing decreased local control in advanced cervical cancer with the
      prolonged overall treatment time of low-dose rate treatment suggest the practical
      advantage of outpatient high-dose rate intracavitary brachytherapy, which uses
      fractionated regimens and shortens overall treatment times. Although high-dose
      rate treatment has not been shown to improve survival compared with low-dose rate
      treatment, its practical advantages may account for its increasing use.

PMID- 8305533
TI  - Platinum analogues in preclinical and clinical development.
AB  - The impact of cisplatin on chemotherapy for solid tumors has led to the synthesis
      of many molecules with platinum as their central building block. These so-called
      platinum analogues have been developed with the obvious goals of improving the
      antitumor activity of cisplatin and hopefully, at the same time, altering the
      dose-limiting side effects of the prototype drug. At least 10 such molecules are
      in clinical development, whereas several others are at various stages of
      preclinical testing.

PMID- 8305534
TI  - Enhancement of thymidylate synthase inhibition.
AB  - Molecular modeling techniques and a knowledge of thymidylate synthase protein
      structure have assisted in the development of several potent new inhibitors of
      thymidylate synthase, the enzyme mediating de novo formation of thymidylate for
      use in DNA synthesis. Information on several new and specific thymidylate
      synthase inhibitors, including ICI-D1694, 1843U89, AG-331, and AG-337, is
      presented. The effects of thymidylate synthase inhibition on the induction of
      thymidylate synthase protein synthesis have raised the question of whether
      thymidylate synthase inhibition alone will be sufficient to provide a desirable
      clinical effect. Formation of a thymidylate synthase-inhibitor complex prevents
      posttranscriptional regulation of thymidylate synthase synthesis, allowing for
      increased thymidylate synthase synthesis and the possibility of drug resistance.
      Therefore, recent efforts have also focused on characterizing this increase in
      thymidylate synthase protein induced by inhibitors of thymidylate synthase and on
      devising combination drug strategies that may prevent the induction of
      thymidylate synthase protein synthesis in addition to inhibiting thymidylate
      synthase activity.

PMID- 8305535
TI  - DNA-topoisomerase inhibitors.
AB  - The topology of DNA is regulated by DNA-topoisomerase enzymes, which induce
      either transient DNA single-strand breaks (topoisomerase I) or DNA double-strand
      breaks (topoisomerase II). The action of several anticancer drugs, eg, DNA
      intercalating agents (ie, anthracyclines, anthracenediones, anthrapyrazoles,
      amsacrines, and ellipticines) and epipodophyllotoxins, appears to be mediated by
      the enzyme topoisomerase II alpha. The action of camptothecins is mediated by
      topoisomerase I. All of these drugs cause the induction of DNA enzyme complexes.
      Some new topoisomerase inhibitors have instead the ability to inhibit the
      catalytic activity of the enzyme without inducing the formation of complexes.
      Inhibition of transcription and DNA replication have been implicated as the most
      likely mechanisms of cytotoxicity. The drugs stimulate DNA cleavage with a
      certain degree of sequence specificity, which is typical for each drug or class
      of drugs. The differences in the location of the cleavage sites may explain the
      different pharmacologic effects of the various topoisomerase inhibitors. Cellular
      resistance to topoisomerase inhibitors is due to decreased intracellular drug
      retention (eg, overexpression of P-170), to a decreased level of topoisomerase
      enzymes, or to mutations that reduce the drug sensitivity of the enzymes.
      Synergistic activity of the combination of topoisomerase I and topoisomerase II
      inhibitors or of topoisomerase inhibitors and radiotherapy has been found to be
      highly dependent on the sequence used.

PMID- 8305536
TI  - Evolution of the therapeutic use of new monoclonal antibodies.
AB  - Peptide or carbohydrate epitopes resulting from aberrant glycosylation, receptors
      for growth, and differentiation signals have recently been reexamined as
      candidates for monoclonal antibody-guided therapy. Microdistribution studies have
      demonstrated the limited penetration of radiolabeled antibodies in tumors.
      Increased tumor capillary permeability has been obtained by pretreatment with
      cytokines or by exploitation of monoclonal antibodies against tumor endothelial
      cells. The use of monoclonal antibodies for combined therapies based on different
      rationales (multiple monoclonal antibodies, monoclonal antibodies plus cytokines,
      and monoclonal antibodies plus drugs) is a recent development, and the
      retargeting of effector cells using hybrid monoclonal antibodies can be
      considered an extension of this approach. A major driving force in the field of
      immunotoxins today is represented by progress in protein engineering. Genes
      encoding various toxins have been cloned, and novel molecules with more desirable
      biologic properties have been produced. Also, genetic engineering techniques help
      in overcoming the major limitation in the clinical use of rodent monoclonal
      antibodies, ie, human antiimmunoglobulin response.

PMID- 8305537
TI  - Defined antigens recognized by T lymphocytes on human tumors.
AB  - Several independent groups have developed methods aimed at identifying antigens
      that are expressed on human tumors and can be recognized by T lymphocytes. The
      positively identified antigens can be presently classified as follows: 1)
      antigens derived from genes whose functions are still unknown that are expressed
      in significant proportions of tumors of various histologic types but not
      expressed in most normal tissues, 2) differentiation antigens expressed in
      melanomas, 3) mucins, 4) viral antigens, and 5) products of abnormal genes
      expressed in tumors. These results are presented with explanations about the
      methodologies used to identify these antigens in the perspective of their use in
      immunotherapy.

PMID- 8305538
TI  - Cellular therapy.
AB  - Attempts to treat cancer by stimulation of cell-mediated responses in the host
      (active immunotherapy) or by adoptive transfer of lymphocytes remain the major
      areas of research in biologic therapy for cancer. Focus in adoptive immunotherapy
      has swung decisively from transfer of lymphokine-activated killer cells together
      with interleukin-2 to transfer of tumor-infiltrating lymphocytes or lymphocytes
      activated against tumor cells by various procedures and transfected or not with
      cytokine genes. These treatment approaches are applicable only in major cancer
      research centers, and they have not yet been proven to be more effective than
      stimulation of host immune responses with vaccines or cytokines, or both.
      Immunotherapy with tumor cells transfected with cytokine genes is a promising new
      approach to active immunotherapy, which is providing new insights into cellular
      responses to tumors. Increased attention is being given to the role of tumor
      derived inhibitors of immune responses, which may limit the effectiveness of
      cellular therapy. Future treatments may need to block these tumor-derived
      inhibitors and provide effective cell-mediated responses against tumors.

PMID- 8305539
TI  - In vitro predictors of clinical response in patients receiving interleukin-2
      based immunotherapy.
AB  - Treatment of cancer patients with interleukin-2 has resulted in clinical
      regression of metastatic disease. The ability to predict which patients will
      respond to therapy could result in more efficacious and possibly less toxic
      treatments. Hence, attempts have been made to correlate patient parameters or in
      vitro characteristics with clinical response to immunotherapy. Some patient
      factors have been identified as prognostically favorable. However, parameters
      modulated by interleukin-2 have not been predictive of clinical outcome. Exciting
      new evidence does exist regarding in vitro characteristics of tumor-infiltrating
      lymphocytes. Measurement of the cytolytic ability of melanoma tumor-infiltrating
      lymphocytes may enhance our understanding of the immune-mediated antitumor
      response and lead to a new generation of selective immunotherapies.

PMID- 8305540
TI  - Retinoids.
AB  - This review highlights recent advances in understanding the mode of action of
      retinoids at the level of molecular and cellular biology in relation to the new
      clinical results achieved with retinoids in various malignancies. All-trans
      retinoic acid has been established in the clinic as a first-line differentiation
      therapy for acute promyelocytic leukemia. Other retinoids, as single agents or in
      combination, generated interesting preliminary results in prevention of or
      therapy for various precancerous and cancerous lesions. These results are
      currently being corroborated in ongoing trials. Retinoids are emerging as a new
      class of anticancer agents with a new molecular target, offering new combination
      therapies.

PMID- 8305541
TI  - Mechanisms of action and toxicity of immunotherapy with cytokines.
AB  - More than two dozen cytokines are now available as recombinant proteins suitable
      for in vivo testing. Several of these novel biologic response modifiers have been
      evaluated in clinical trials, and a few have been proven to be effective.
      Interferon-alpha is often used to treat low-grade lympho- and myeloproliferative
      diseases, and it is undergoing evaluation as treatment of several solid tumors.
      Interleukin-2 was recently approved by the US Food and Drug Administration for
      the treatment of patients with metastatic renal cell carcinoma. Other cytokines
      that are active as antitumor agents in experimental animals have failed to enter
      the mainstream of oncologic practice because of poor results in preliminary
      trials and, in some instances, prohibitive toxicity. This review focuses on the
      cellular mechanisms underlying cytokine-induced tumor regression and toxicity.

PMID- 8305542
TI  - Breast.

PMID- 8305543
TI  - Therapeutic modalities.

PMID- 8305544
TI  - Epidemiology, early detection, and prevention of breast cancer.
AB  - Major advances in the past year in the etiology, early detection, and prevention
      of breast cancer are reviewed. Progress has been made in the genetic epidemiology
      of breast cancer. A major gene locus has been identified among cancer families
      with predominantly breast or ovarian cancer, or both. Hormonal factors associated
      with breast cancer continue to be studied. Recent reports suggested that
      exogenous hormone therapy is associated with only moderate or no excess risk of
      breast cancer. With respect to early detection, controversy arose regarding the
      benefit of screening for women younger than 50 years of age. The Canadian
      National Breast Screening Study showed no decrease in breast cancer mortality for
      women 40 to 49 years old who were screened annually compared with women who had a
      baseline breast examination. An international workshop was convened to review
      results of breast cancer screening trials with emphasis on women younger than 50
      years of age. Chemoprevention trials for the primary prevention of breast cancer
      are underway in North America and Europe. Agents under investigation include
      tamoxifen and fenretinide. Prevention of breast cancer will also be examined in
      two trials with multiple disease end points; one is an intervention with low
      dietary fat, and the other is an intervention with specific micronutrients.

PMID- 8305545
TI  - Pathology of preinvasive and excellent-prognosis breast cancer.
AB  - Recent advances in breast cancer treatment have made recognition of different
      prognostic groups mandatory. In addition, further experience with screening
      detected lesions has resulted in the definition of new associations. Therapeutic
      approaches to these frequently microscopic lesions continue to be the source of
      much debate. The subtyping of ductal carcinoma in situ is also an area of
      continuing controversy. This article reviews recent studies of excellent
      prognosis carcinomas as well as premalignant and other histologically defined
      lesions that indicate an increased risk for the development or recurrence of
      carcinoma. Advances in fine needle aspiration biopsy and in hormone receptor
      assays are also reviewed.

PMID- 8305546
TI  - Surgery of early breast cancer.
AB  - Randomized trials of treatment have evaluated the role of radiotherapy after
      breast-preserving surgery for both in situ and invasive cancer. These trials
      provide treatment guidelines and identified "show biz" questions relating to both
      therapy and biology. A trial of systemic treatment of premenopausal women with
      node-positive disease provided compelling reasons to always determine estrogen
      receptor status before determining adjuvant systemic treatment. Additional data
      on pathology, needle biopsy, and surgical techniques provide important
      information for surgeons. New data on breast cancer biology in young women and
      data suggesting that mastectomy rates are still higher than necessary provide
      issues on which surgeons can reflect. Evidence that supports marrow biopsy for
      staging at the time of surgery is important for surgeons. Psychosocial data are
      partly reassuring in that mastectomy patients, if they choose the procedure
      themselves, may not be worse off. Finally, a sobering report of the devastating
      effects of late diagnosis came from Nigeria.

PMID- 8305547
TI  - Radiation therapy for breast cancer.
AB  - Local regional control, despite its lack of impact on survival, continues to be
      recognized as an important end point in and of itself. In addition to recent
      updates on conservation studies demonstrating this dichotomy, local regional
      radiation is now playing an important role in the management of advanced breast
      cancer postmastectomy. The most extreme example of this importance is its
      inclusion in autologous bone marrow transplantation programs. Documentation of
      the long-term outcome of breast or chest wall radiation, in terms of both
      complications and treatment failures, appears increasingly in this year's
      literature. With sophisticated biostatistical analysis of all factors predicting
      for both local failure and late complications, patient selection for these
      treatments should become easier for both the woman and her physician.

PMID- 8305548
TI  - Systemic adjuvant therapy for breast cancer.
AB  - The use of systemic (drug) therapy postoperatively reduces the risk of relapse
      and death for patients with resectable invasive breast cancer. The Early Breast
      Cancer Trialists' Collaborative Group overview analysis confirmed the benefits of
      both polychemotherapy and tamoxifen in broad subgroups of patients. It remains a
      challenge, however, to quantify the risk of relapse and the benefit of therapy
      for individual patients. If the ipsilateral lymph nodes are free of metastases
      and the tumor is infiltrating ductal or lobular in histology and less than 1 cm
      in diameter, the risk of relapse is low, so the benefits of standard treatments
      are too small to warrant routine use. For node-negative patients with larger
      tumors or for those with positive lymph nodes, the benefits of therapy are
      significant, although many of these individual patients will not relapse. Hence,
      better prognostic methods, improving the accuracy of predicting an individual
      patient's risk, could allow for more rational treatment recommendations. The most
      widely used polychemotherapy combination incorporates three drugs:
      cyclophosphamide, methotrexate, and fluorouracil. The substitution or inclusion
      of doxorubicin, which is somewhat more toxic than the cyclophosphamide,
      methotrexate, and fluorouracil regimen, is justifiable in subsets of patients at
      higher risk of relapse, eg, those with metastatic involvement of four or more
      axillary lymph nodes. Because higher dose intensity (the amount of drug given per
      unit time) of chemotherapy improves relapse-free survival, phase II clinical
      trials are testing various dose-intensification strategies, and phase III trials
      are underway to determine their comparative efficacy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8305549
TI  - Metastatic breast cancer.
AB  - The place of tamoxifen in the treatment of metastatic breast cancer is being
      challenged by the development of less estrogenic antiestrogens. New inhibitors of
      aromatase and estrone sulfatase have been reported. Anthrapyrazoles are new
      cytotoxic agents with high activity and low toxicity. Uncertainty about the
      optimal duration of chemotherapy continues. Methods to intensify chemotherapy,
      enabled by bone marrow support techniques, continue to be studied, but a routine
      role for this approach in palliative treatment of metastatic disease has not been
      established. Active specific immunotherapy appears to be practicable following
      identification of defined tumor-associated immunogens. Evidence for the ability
      of bisphosphonates to reduce morbidity from bone metastases continues to
      accumulate.

PMID- 8305550
TI  - Psychosocial aspects of breast cancer.
AB  - Over the past year, several research areas have been noteworthy. This article
      discusses decision making related to breast cancer treatment, the effects of
      treatment on measures of psychological distress, and studies related to quality
      of-life among breast cancer patients. In addition, an area of continued interest
      involves breast cancer survival as a function of psychological distress or
      psychological intervention. This article summarizes and critiques publications in
      these areas.

PMID- 8305551
TI  - [The infrequency and exceptionality of infectious pathology].

PMID- 8305552
TI  - [Seroprevalence of Coxiella burnetii and Rickettsia conorii infection in the
      province of Soria].
AB  - BACKGROUND: Determine the antibodies prevalence against Coxiella burnetii and
      Rickettsia conorii in Soria (Spain). METHODS: By an indirect immunofluorescence
      test we examined sera samples for antibodies (IgG, IgM and IgA) against C.
      burnetii (phase II, formolized antigen) and R. conorii (moroccan strain). The
      test has been applied to 298 sera (150 men and 148 women) from Soria (Spain). The
      age of the study population ranged between 2 and 91 years. The results were
      considered positive when the titres were greater than or equal to 1/80 for C.
      burnetii and 1/40 for R. conorii. RESULTS: Antibodies against C. burnetii were
      present in 20.8% of the examined sera, 8.8% for women (13/148) and 32.7% for men
      (49/150). We demonstrated titers of antibodies upper to 1/40 in all age groups,
      and a greater number of positive results in the persons older than 40 years old
      (p = 0.0001). In all areas we detected positive results and in many of these
      areas, the positivity was high (38%). We demonstrated positive results against R.
      conorii in 5% of the people (4.7% for women and 5.3% for men). More than 90% of
      the positive cases was present in the eastern part of Soria, and in an small
      area, the positivity was 20%. CONCLUSIONS: These results confirm a high
      prevalence of antibodies against C. burnetii in the Soria people, and the
      existence of R. conorii infection in this area of Spain with a particular
      distribution. We believe that it is very important to establish an
      epidemiological surveillance for the detection of clinic cases.

PMID- 8305553
TI  - [Ciprofloxacin resistance in gram negative bacilli. Epidemiologic aspects].
AB  - BACKGROUND: The aim of the present was to study the resistance to ciprofloxacin
      (CIP) in gram negative bacilli (April 1990-March 1992) and to determine the
      temporary distribution of the resistant strains by species, samples and
      departments. METHODS: Seven thousand four hundred seventy-eight samples were
      studied. The identification and determination of the sensitivity was performed by
      the PASCO (Difco) system. Haemophilus spp. and Campylobacter spp. were excluded
      from the study. The microorganisms with CIM 2 mg/l were considered as resistant
      (CIPr). RESULTS: Four hundred eighty-one CIPr isolations were identified (6.4%).
      With regard to the percentage of resistant strains, the species with the highest
      were: Providencia stuartii (50%); Pseudomonas cepacia (44.4%); Xanthomonas
      maltophilia (26.9%); Acinetobacter baumannii (25.8%); Pseudomonas aeruginosa
      (16%); Citrobacter freundii (12.5%); Serratia marcescens (8.4%); Enterobacter
      cloacae (5.8%) and Escherichia coli (4.3%). With respect to the absolute number
      of resistant strains, the most frequent resistant strains were: P. aeruginosa
      (205), E. coli (144), and A. baumannii (41). Isolation of E. coli and A.
      baumannii CIPr increased over the study period. Forty-four point five percent of
      the E. coli CIPr were of extrahospitalary origin; most of the A. baumannii
      (92.9%) and P. aeruginosa (77.6%) in contrast were of intrahospitalary origin.
      CONCLUSIONS: P. aeruginosa, E. coli, and A. baumannii are the most frequently
      resistant species. The frequency of isolation of resistant strains of E. coli and
      A. baumannii significantly increased (p < 0.001) over the two years of the study.

PMID- 8305554
TI  - [Yield of detection of Clostridium difficile toxin versus stool culture in the
      study of nosocomial diarrhea].
AB  - BACKGROUND: The aim of the study was to determine whether the detection of
      Clostridium difficile toxin in stools may be more profitable than conventional
      stool cultures for the etiologic study of nosocomial diarrhea and to analyze what
      risk factors favor the development of nosocomial diarrhea by C. difficile.
      METHODS: The presence of enteropathogens and A and B toxins of C. difficile were
      investigated (by monoclonal antibody enzymoimmunoassay) in stools of patients
      with nosocomial diarrhea. A series of patients simultaneously admitted without
      diarrhea were selected as the control group. RESULTS: During a 6 month period 92
      patients with nosocomial diarrhea and 82 controls without diarrhea were studied.
      The C. difficile toxin was detected in 8 of these 174 patients (4.6%). Eight
      point seven percent of the nosocomial diarrheas were related with C. difficile
      while only 1% were due to an enteropathogen (Salmonella enteritidis). C.
      difficile toxin was not detected in any patient who did not have diarrhea. In
      comparison with the patients with diarrhea due to other causes, the patients with
      diarrhea by C. difficile had more frequently received antibiotics over the
      previous 7 days (57 vs 88%) and had been hospitalized for a longer time (> or = 7
      days) (58 vs 88%) (p < 0.05). CONCLUSIONS: In the author's institution infection
      by Clostridium difficile is the most frequent cause of nosocomial infectious
      diarrhea, especially in patients admitted for a prolonged time or who receive
      antibiotics. The routine investigation of enteropathogens in the cases of
      nosocomial diarrhea does not seem justified while the detection of the A and B
      toxins of C. difficile may be more profitable.

PMID- 8305555
TI  - [Bite wound infections: study of 22 hospitalized patients].
AB  - BACKGROUND: To study the characteristics of bite wounds with unfavorable
      evolution, developing infectious complications that requires hospital admission.
      METHODS: The data from 22 patients admitted to the Ciudad Sanitaria Vall d'Hebron
      hospital for the above mentioned reason over the last 5 years were reviewed.
      RESULTS: The patients (8 males, 8 females and 6 children) were bitten by 10 dogs,
      6 cats, and 6 men with predominance of the wound site being in the upper limb
      (10) followed by the lower limbs (6), head or face (5) and exceptionally on the
      breast (1). The most frequent clinical manifestation was abscess and/or
      cellulitis (13) and adenopathies or lymphangitis (4); 5 patients presented
      osteoarticular involvement including 3 bone fractures due to human aggression.
      With regard to the etiology of infection, the common bucal flora bacteria were
      isolated in all the cases; Pasteurella multocida in 15/16 animal bites, Eikenella
      corrodens associated to streptococcus in 5/6 human bites, Fusobacterium spp. (5),
      Bacteroides spp. (3) and Peptococcus sp. (1). The most frequently administered
      antibiotics were gentamycin (15), penicillin (13), cloxacillin (5) and
      clindamycin (4). The evolution was favorable, although slow in many cases, with
      sequelae in 3 patients. CONCLUSIONS: It is very difficult to foresee in which
      cases infectious complications will develop in bite wounds. According to the
      authors' experience, in the case of deep wounds the bacteria implied come from
      the mouth of the aggressor. Careful cleansing, rapid administration of an
      adequate antibiotic and clinical control being the most recommendable procedure.

PMID- 8305556
TI  - [Analysis of 40 cases of otomycosis].
AB  - AIM: Otomycosis is a rare clinical process, with peculiar characteristics
      concerning its etiology and presentation, depending on the geographic area. In
      order to determine the most common agents, the clinical and epidemiological
      aspects in mycotic external otitis, 40 episodes detected during one year period
      were analyzed. METHODS: Forty patients with otomycosis diagnosed (positive
      microbiological culture) were studied. Fungi were identified in accordance with
      morphological and biochemical criteria. RESULTS: Candida parapsilosis (42.9%) and
      Aspergillus niger (35.7%) were the commonest agents. In three episodes were found
      associated bacterial flora. The patients were males (60.0%), between the ages of
      31-40 (35.0%) and over 50 years old (37.5%). The symptoms were the usual for
      these processes: serous fluid, otalgia and itching. The majority of the episodes
      occurred in the summer (57.5%) and autumn (30.0%), due to sea bathing (90.0%),
      trauma (27.5%) and prior antimicrobial treatment (40.0%). CONCLUSIONS: Candida
      parapsilosis is as an important pathogen of otomycosis in our environment, though
      the participation of Aspergillus niger is also remarkable, as it happens in other
      geographic areas. The contact with seawater and the antimicrobial treatment are
      the main factors which favor the infection; climatical conditions could cooperate
      to it in great extent. The observed symptoms are similar to the bacterial otitis,
      but of lesser intensity.

PMID- 8305557
TI  - [Problems found in the isolation of mycelial fungi (Fusarium solani) from blood
      culture (Bacter NR-860)].
AB  - BACKGROUND: F. solani fungemia is unusual. Patients at risk are immunosuppressed,
      have underlying malignancy or severe debilitating diseases. METHODS: We report
      two cases of F. solani fungemia in two non neutropenic patients who had been
      treated with wide-spectrum antibiotics an/or systemic corticosteroids, parenteral
      nutrition and intravenous lines. Bactec NR-860 (Becton-Dickinson) system was
      used, and growth was detected in aerobic conditions (between 3-7 days of
      incubation). RESULTS: Removal of the catheters with or without i.v. amphotericin
      B were used successfully. CONCLUSION: The spectrum of Fusarium sp. fungemia is
      discussed. Current available antifungal therapy is also reviewed.

PMID- 8305558
TI  - [Bacteremia caused by Mycobacterium tuberculosis and/or Mycobacterium avium
      detected by the non-radiometric Bactec system].
AB  - BACKGROUND: To assess the utility of Bactec non-radiometric system in detecting
      disseminated mycobacteremia. METHODS: Blood cultures are processed using the
      Bactec NR 660/HPS system. Incubation of the NR6A vials, from HIV infected
      patients, is prolonged for 6 weeks and read once a week. After the 14th day of
      incubation a growth value > or = 30 is considered positive. RESULTS: Mycobacteria
      were recovered from 80 blood cultures from 32 human immunodeficiency virus
      infected patients. The mean time required to detect growth was 37.8 days (range
      20-45). Mycobacterium tuberculosis was isolated from 18 patients and
      Mycobacterium avium from 14. In 12 patients (37.5%) blood culture was the first
      or the only positive specimen. CONCLUSIONS: Prolonged incubation of NR6A medium
      has proved to be a suitable method for detecting mycobacteremia.

PMID- 8305559
TI  - [Pathogenicity and virulence mechanisms described in thermo-resistant
      Campylobacter bacteria].

PMID- 8305560
TI  - ["Antisense": microbiological therapy and diagnosis].

PMID- 8305561
TI  - [Gram positive microorganism with atypical sensitivity to imipenem].

PMID- 8305562
TI  - [Polyadenopathies in an HIV-positive patient with multiple tattoos].

PMID- 8305563
TI  - [Laboratory diagnosis of typhoid fever: the Widal test or Salmonella typhi
      culture?].

PMID- 8305564
TI  - [Acute brucellosis and HIV infection: a new particularity].

PMID- 8305565
TI  - [Haemophilus influenzae resistance and cefaclor].

PMID- 8305566
TI  - [Comparison of 2 culture media for the isolation of Aeromonas spp. from feces].

PMID- 8305567
TI  - [Isolation of Flavimonas oryzihabitans from cultured blood from a patient with a
      Hickman catheter].

PMID- 8305568
TI  - [Idiopathic esophageal ulcer cured with corticosteroids in a patient with HIV
      infection].

PMID- 8305569
TI  - Preventing the sexual spread of HIV infection--what have we learned?

PMID- 8305570
TI  - Haemophilus ducreyi.
AB  - Genital ulcer disease as a risk factor for HIV transmission has become apparent
      in the fight against AIDS. In poor communities in developing countries with
      people living under low hygienic conditions chancroid is often reported to be the
      most common form of genital ulcer. It is caused by Haemophilus ducreyi; a
      fastidious bacterium, notoriously difficult to grow in the laboratory. Apart from
      a few small micro-epidemics from time to time the disease, which has interesting
      immunological aspects, is now rare and almost forgotten in most industrialized
      countries. This may be part of the reason why there is no simple and inexpensive
      diagnostic test available yet that would be useful in the low-resource settings
      where chancroid is prevalent. The present review focuses on the diagnosis and
      pathogenesis of chancroid.

PMID- 8305571
TI  - Cytomegalovirus retinitis: diagnosis and treatment.
AB  - Cytomegalovirus (CMV) is a non-pathogenic organism in the immunocompetent, but is
      a major cause of morbidity and mortality amongst patients with AIDS, and the
      retina is the commonest site of infection. If left untreated, patients with CMVR
      will develop disease in their second eye and ultimately become blind. However,
      with correct diagnosis and treatment useful vision can be maintained in the
      majority of cases. Fifteen to 20% of patients with AIDS will contract
      cytomegalovirus retinitis (CMVR) and this may be the AIDS-defining diagnosis
      though more commonly it occurs months after the diagnosis of AIDS. Given the
      increasing number of HIV positive patients and their longer survival, it is
      likely that CMVR will become an increasingly prevalent condition. In these
      patients loss of sight from CMVR has devastating consequences in terms of loss of
      independence and quality of life and therefore ophthalmologists and physicians
      should be aware of the presenting characteristics of CMVR, be familiar with
      therapy and its complications, and be able to recognize relapsing infection.

PMID- 8305572
TI  - Desire for unprotected intercourse preceding its occurrence: the case of young
      gay men with an anonymous partner.
AB  - One sample of young gay men (n = 219) and 3 samples of older gay men (n = 219, n
      = 207, and n = 88) recalled a sexual encounter in which they had engaged in
      unprotected anal intercourse. Throughout the evening of the encounter, desire
      specifically for unprotected intercourse had generally been less common the more
      distant the relationship with the partner. Young men having sex with an anonymous
      partner were an exception to this pattern, however: they had desired unprotected
      intercourse almost as commonly as had young men having sex with a lover. The
      extent to which unprotected intercourse is premeditated in young men with an
      anonymous partner may make it particularly hard to modify their behaviour. This
      group had also been in an especially negative mood state at the start of the
      evening, suggesting the importance of trying to inculcate non-destructive ways of
      dealing with negative mood states.

PMID- 8305573
TI  - PPNG at St Thomas' Hospital--a changing provenance.
AB  - Between 1986 and 1992, 15% of all cases of penicillinase-producing Neisseria
      gonorrhoeae (PPNG) notified in the UK were seen at our central London clinic.
      During this time the geographical provenance of PPNG has changed. Africa and SE
      Asia have been supplanted by the Caribbean as the predominant source, with 21.4%
      of all cases being directly imported from there in 1992. If all gonococcal
      infections acquired outside the UK had been assumed to be PPNG, together with
      those occurring in patients with family origins in Africa or SE Asia, some 60% of
      cases of PPNG could have been predicted before laboratory confirmation of
      resistance. There is little evidence that PPNG has become endemic in the United
      Kingdom.

PMID- 8305574
TI  - The reliability and validity of a symptom checklist for use in HIV infection: a
      preliminary analysis.
AB  - The aim of the study was to determine the reliability and validity of a self
      report symptom checklist designed for use in HIV infection. One hundred and
      seventy-one gay men completed a 28-item symptom checklist which produces 3
      dimensions: physical, cognitive and psychological. The validity of each dimension
      was examined by comparing scores on the checklist with indices of disease
      progression and previously validated psychological scales. People with more
      advanced HIV disease had higher scores on the physical and cognitive checklists,
      though the psychological scale was not related to disease stage. All the scales
      showed moderate correlations with measures of psychological health. Examination
      of individual item responses suggested that patients over-reported the presence
      of some symptoms. Although individual items should be interpreted with caution,
      the overall scores of the RSC are reliable and valid as measures of subjective
      health status in HIV infection. The importance of psychological factors in the
      reporting of symptoms suggests that symptom checklists should be interpreted in
      the light of adequate measures of psychological state.

PMID- 8305575
TI  - Cytomegalovirus retinitis and AIDS in Edinburgh.
AB  - The medical records, retinal drawings and fundus photographs of all patients with
      cytomegalovirus retinitis (CMVR) and AIDS in Edinburgh between 1986-1992 were
      reviewed to determine the efficacy of treatment in preserving vision.
      Ophthalmoscopic features of CMVR were observed in 32 eyes of 24 patients with
      AIDS, 19 males and 5 females. HIV transmission in this group was by homo/bisexual
      contact (16), injection drug use (7) and blood transfusion (1). Unilateral
      blurring was the commonest visual symptom although 9 (38%) patients had no visual
      symptoms. All patients presented with a corrected visual acuity of 6/12 or better
      in at least one eye. Following treatment with systemic ganciclovir or foscarnet
      16 patients (66%) developed toxic side-effects of therapy and 13 (54%)
      experienced a recurrence of CMVR. Four (17%) patients developed a retinal
      detachment in one eye. The mean survival was 8.3 months after the diagnosis of
      CMVR. At final follow-up, between 2-26 months after the diagnosis of CMVR, 21
      (87.5%) patients retained useful vision (6/18 or better) although 3 (12.5%) were
      effectively blind (less than 6/60). We conclude that with prompt diagnosis and
      treatment of CMVR vision can be preserved in the majority of cases.

PMID- 8305576
TI  - Human immunodeficiency virus infection of early passage cervical epithelial
      cultures.
AB  - Women are infected with HIV in increasing numbers; the predominant mode of spread
      is through heterosexual transmission. Little is known regarding the mechanism of
      HIV transit through the female genital tract. We investigated whether early
      passage cervical epithelial cells could be directly infected with HIV-1LAI. Virus
      production was measured using the reverse transcriptase (RT) assay and direct
      assay for syncytia-forming units. In-situ hybridization was performed on infected
      cervical cell cultures. Immunostaining was carried out using a monoclonal
      antibody to leukocyte common antigen (LCA). Virus was recovered in the
      supernatants of all infected cervical cultures. Localization of HIV infection
      using in-situ hybridization identified rare cells in the population which gave a
      strong signal. These infected cells had a lymphoid morphology and were also
      detected using immunostaining for LAC. Cervical epithelial cells were uninfected
      in this in vitro model; cells in this population which supported viral
      replication were most likely of the macrophage/monocyte lineage.

PMID- 8305577
TI  - Vaginal cytomegalovirus infection in a woman with AIDS.

PMID- 8305578
TI  - Heterosexual transmission of HIV: a global view a decade later.

PMID- 8305579
TI  - Emerging patterns of heterosexual HIV infection and transmission. Closing
      statement.

PMID- 8305580
TI  - Emerging patterns of heterosexual HIV infection and transmission. Closing
      remarks.

PMID- 8305581
TI  - Coupling of HPLC with 19F- and 1H-NMR spectroscopy to investigate the human
      urinary excretion of flurbiprofen metabolites.
AB  - Results of an on-line HPLC-NMR analysis of human urine from a volunteer
      administered the anti-inflammatory drug flurbiprofen are reported. The two major
      human urinary metabolites, namely the glucuronides of flurbiprofen and of 4'
      hydroxyflurbiprofen, have been identified using 1H- and 19F-NMR spectroscopy. In
      vivo conjugation of the racemic drug and its metabolites with D-glucuronic acid
      results in diastereomeric molecules which give resolved NMR spectra thereby
      permitting the diastereomeric proportions to be evaluated. The cause of the
      observed deviation from equal proportions is discussed. This study represents the
      first use of both 19F- and 600 MHz 1H-NMR spectroscopy coupled to HPLC.

PMID- 8305582
TI  - HPLC method for rapid determination of acetylator phenotype by measuring urinary
      caffeine metabolites.
AB  - A validated reversed-phase high-performance liquid chromatographic (RP-HPLC)
      method is developed for the selective and rapid determination of two major
      metabolites of caffeine, namely 5-acetylamino-6-formylamino-3-methyluracil (AFMU)
      and 1-methylxanthine (MX) from human urine. HPLC separation is achieved by means
      of a Supersphere-60 RP-Select B (4 microns) analytical column using a non-linear
      gradient elution programme of 70-95% solvent B (2.5% acetic acid-methanol, 60:40,
      v/v) in solvent A (water-acetonitrile, 80:20, v/v). A selective UV detection
      method is used for determination of AFMU, MX and internal standard with readings
      at 284, 268 and 248 nm, respectively. Urine samples are prepared for measurement
      by a simple chloroform-diethyl ether (80:20, v/v) extraction. The assay is
      validated with respect to linearity, sensitivity, accuracy, precision and system
      suitability. All validation parameters are found to be within the required
      limits. The limit of detection of AFMU and MX is found to be 50 ng/200
      microliters urine. Calibration curves show good linearity between 0.1 and 5
      micrograms/200 microliters urine concentration range for both metabolites. The
      assay is sufficiently sensitive and rapid (4.5 min chromatographic run) to be
      applied for routine monitoring of change in AFMU/MX molar ratio, indicating
      acetylation phenotype and change of caffeine metabolism in clinical cocktail
      studies.

PMID- 8305583
TI  - Determination of cyclodextrins in serum by reversed-phase chromatography with
      pulsed amperometric detection and a membrane reactor.
AB  - A high-performance liquid chromatographic method has been developed for the
      determination of cyclodextrins (CDs) in serum. The method involves solid-phase
      extraction of CDs, separation on a C18 reversed-phase column using a mixture of
      water, tetrahydrofuran and methanol as an eluent, eluent pH modification with a
      cation-exchange membrane reactor surrounded by 1.5 M sodium hydroxide solutions,
      and pulsed amperometric detection (PAD) with a gold working electrode. The solid
      phase extraction on a C18 bonded-silica column was effective for removing the PAD
      sensitive components in serum. The calibration graphs constructed by internal
      standard method were linear over the range 6.25-200 pmol of CDs in serum. The
      detection limits for CDs were about 5 pmol at a signal-to-noise ratio of 3.

PMID- 8305584
TI  - Determination of polyethylene glycols by high-performance liquid chromatography
      thermospray mass spectrometry.

PMID- 8305585
TI  - Liquid chromatographic determination of indapamide in the presence of its
      degradation products.

PMID- 8305586
TI  - Degradation profile and reversed-phase LC method development of the
      antiinflammatory drug, Ro 24-5913.

PMID- 8305587
TI  - HPLC analysis of mildronate and its analogues in plasma.

PMID- 8305588
TI  - Enhanced robotic dissolution system with concurrent off-line analysis.
AB  - A Zymate II robotic dissolution system was modified by addition of a liquid
      chromatography (LC) system equipped with an Isco ISIS autosampler. Using the
      Concurrent EasyLab programming language, operation of this LC system was
      integrated into the main robotic dissolution procedure. This enabled simultaneous
      dissolution sampling and LC analysis of standard and pre-pulled sample solutions.
      The resulting dual-tasking system effects considerable efficiency of operation
      and results in significant time savings. Comparison of the robotic and non
      robotic data indicate good correlation and statistically insignificant
      differences at the 95% confidence level. Validation studies confirm linearity and
      precision of the quantitative LC method, accuracy and precision of volume and
      temperature measurements and negligible vessel-to-vessel carryover.

PMID- 8305589
TI  - A sensitive enzyme immunoassay (EIA) for quantitation of the topical anti
      inflammatory agent SCH 40120 in unextracted human plasma.
AB  - SCH 40120 is a potent acute anti-inflammatory agent under development for topical
      treatment of dermal inflammatory and allergic disorders such as atopic
      dermatitis, contact dermatitis and psoriasis. In order to support percutaneous
      absorption studies, a competitive enzyme immunoassay (EIA) was developed to
      determine SCH 40120 in unextracted plasma samples. SCH 38280, a carboxylated
      analogue of SCH 40120, was used as the hapten and conjugated with bovine
      thyroglobulin (Thy). The hapten-Thy conjugate was used as the immunogen to
      immunize rabbits for antibody production. The hapten was also coupled to
      horseradish peroxidase (HRP) to form SCH 38280-HRP, which was used as the tracer.
      The EIA can detect SCH 40120 concentrations as low as 50 pg ml-1 of plasma, and
      can reliably quantitate SCH 40120 in plasma samples from 100 pg ml-1 to 10 ng ml
      1 with good linearity, accuracy and precision. A variety of structurally related
      compounds and potential metabolites did not significantly cross-react with the
      antibodies, except for a few analogues. The availability of this sensitive assay
      makes it possible to evaluate the pharmacokinetics of SCH 40120 in man.

PMID- 8305590
TI  - Stereochemistry of pipecolic acid found in the urine and plasma of subjects with
      peroxisomal deficiencies.
AB  - Recently it was found that normal adults excrete pipecolic acid primarily as the
      D-enantiomer even though it is present in the blood stream mainly as the L
      enantiomer (i.e. > 98% L). This study of pipecolic acid stereochemistry was
      extended to subjects with peroxisomal deficiencies since they are known to have
      high levels of pipecolic acid in their physiological fluids. Also, pipecolic acid
      stereochemistry was examined in young normal subjects since this group was not
      considered previously. It was found that the stereochemical composition of
      pipecolic acid in plasma was very similar for all subjects tested (i.e. > 98% of
      the L-enantiomer). However, the stereochemical composition of excreted pipecolic
      varied considerably. Urine samples from subjects with the most severe peroxisomal
      deficiency, i.e. cerebralhepatorenyl (Zellweger) syndrome (CHRS) contained little
      D-pipecolic acid. In fact the enantiomeric ratios for pipecolic acid in the urine
      and plasma of these subjects were very similar. This was not the case for normal
      subjects. Levels of D-pipecolic acid in the urine of subjects with 'less severe'
      peroxisomal deficiencies tended to be somewhat higher but they did not approach
      the levels found in normal adults. Several possible reasons for these results are
      discussed.

PMID- 8305591
TI  - Determination of captopril in pharmaceutical samples by flow injection analysis.
AB  - A flow injection spectrophotometric method for the determination of captopril
      involving measurement of the absorbance of the captopril complex with
      palladium(II) in a 0.12 M HCl medium at 400 nm is presented. The calibration
      graph was linear over the range 2 x 10(-5)-6 x 10(-4) M. The sampling frequency
      was 90 h-1 with sample injections of 70 microliters. The proposed method was
      applied to the determination of captopril in pharmaceutical samples.

PMID- 8305592
TI  - Kinetic fluorimetric determination of promethazine by a stopped-flow mixing
      technique.
AB  - The oxidation of promethazine to its corresponding fluorescent sulphoxide was
      used to develop a novel kinetic fluorimetric method for the determination of this
      drug. The use of a stopped-flow mixing technique makes use of an oxidizing
      reagent unnecessary because the oxidation is rapidly carried out by dissolved
      oxygen. The method is simple and fast as it only requires a few seconds to obtain
      kinetic data which allows ready application to routine analyses. The calibration
      graph is linear over the range 0.5-80 micrograms ml-1 and the precision (%RSD) is
      close to 2%. The method was applied to the determination of promethazine
      hydrochloride in two pharmaceutical preparations.

PMID- 8305594
TI  - Non-invasive sampling of lactic acid ions by iontophoresis using chloride ion in
      the body as an internal standard.
AB  - Non-invasive sampling of lactic acid, as a model endogenous compound, through
      hairless rat skin by iontophoresis was investigated using a two-chamber
      iontophoretic diffusion cell equipped with platinum electrodes and a pulse
      depolarization iontophoretic system. Chloride ion in the body was used as an
      internal standard. First, an in vitro experiment on the permeation of lactate and
      chloride ions through hairless rat skin was carried out to determine the flux
      ratio of these ions. The cathode side of the cell (dermis side) was filled with
      physiological saline containing lactic acid (0.5556, 1.111, 1.667 or 2.222 mmol
      cm-3) and the anode side (epidermis side) with phosphate buffer (pH 7.4). The
      amount of lactate and chloride ion permeated from the dermis side to the
      epidermis side through the skin at a constant current of 3.0 mA was determined
      using an automatic lactic acid analyser and high-performance ion chromatography,
      respectively. For construction of a calibration curve of lactic acid in the
      dermis side, the ionic mobility ratio of lactic acid/chloride ion (UCl/Ulac) was
      determined using a computer simulation program from the flux ratio of lactic acid
      and chloride ion and the applied concentration of lactic acid in the dermis side.
      Second, an in vitro non-invasive sampling experiment of lactic acid through rat
      skin was carried out at a constant current of 2.0 or 3.0 mA and 2.222 or 1.111
      mmol cm-3 of lactic acid in the dermis side, respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8305593
TI  - Raised transaminase activity of blood plasma from rats with experimentally
      induced kidney damage detected by spin-echo 1H-NMR spectroscopy.
AB  - We report the application of spin-echo 1H-NMR spectroscopy to the detection of
      raised plasma transaminase activity in rats treated with the nephrotoxic
      cephalosporin antibiotic cephaloridine (CPH). Spin-echo 1H-NMR analysis of
      lyophilized plasma, reconstituted in H2O reveals a doublet at delta 1.48 for
      alanine. However when samples were reconstituted with 2H2O we noted that in
      samples from CPH-treated rats (but not in control samples) there was a variable
      degree of appearance of a singlet at delta 1.47 together with a reduction in the
      doublet at delta 1.48. We suggest that this is due to the release of
      transaminases from damaged tissue which, via a reversible conversion of alanine
      to pyruvate, causes selective deuteration of alanine at the alpha-hydrogen (alpha
      CH) position. This observation suggests that these 1H-NMR spectral patterns are
      dependent on the level of plasma transaminases and this may provide a novel
      indicator of tissue damage.

PMID- 8305595
TI  - Size distribution of liposomes by flow field-flow fractionation.
AB  - The applicability of field-low fractionation (FFF) to the characterization of
      liposomes is discussed and theoretically described. Because of fundamental
      differences in their driving forces, sedimentation FFF and flow FFF measure
      different vesicle properties. Sedimentation FFF, although used previously to
      measure vesicle sizes and size distributions, is fundamentally a technique that
      measures the effective mass and mass distribution of particles. It is sensitive
      to small changes in the effective mass of either the biomembrane or its
      encapsulated load and thus is likely to be useful in characterizing such
      properties as drug loading, biomembrane volumes and areas, and distributions of
      these properties. Size characterization by sedimentation FFF can only be done by
      deducing size from effective mass. Flow FFF, by contrast, provides a direct
      measurement of vesicle size and size distribution. After demonstrating the high
      resolution and relative accuracy of size measurement of flow FFF by the
      separation of polystyrene latex standards, flow FFF was applied to two
      preparations of DSPC-DSPA liposomes that were sonicated under different
      temperature conditions. Fractograms and size distributions are reported as a
      function of sonication time. The rapid elimination of a large diameter tail to
      the distribution is shown to constitute a major mechanism for distribution
      narrowing. Finally, results are provided bearing on the reproducibility of size
      distribution measurements by flow FFF.

PMID- 8305596
TI  - On-line monitoring of urea in effluent liquid during haemodialysis.
AB  - An analytical system specially built for on-line urea monitoring is reported.
      Measurements are carried out in the effluent of a haemodialysis machine. The
      measuring system employs the dialyser inflow stream as a carrier solution channel
      in a continuous fashion. The analyser periodically samples the outflow stream of
      the dialyser by means of an automatic injection valve. The analyser features a
      bioreactor consisting of immobilized urease and a gas-diffusion module. It is
      through this module that the urea is converted to ammonia gas which is
      transferred to another carrier channel, this transports the ammonium ion to a
      tubular, all-solid-state, ion-sensitive electrode. A timer controls the
      transport, injection, the measuring and the recording subsystems. The analyser
      has been used during actual haemodialysis sessions. Urea clearances were also
      measured in batch, using conventional spectrophotometric clinical equipment. The
      correlation between both methodologies was sufficient to confirm the usefulness
      of the developed on-line analyser to monitor the optimal length of haemodialysis
      sessions.

PMID- 8305597
TI  - Stopped-flow photometric determination of clavulanic acid in pharmaceutical and
      serum samples.
AB  - The stopped-flow mixing technique was used to develop a simple, fast kinetic
      method for the determination of clavulanic acid by reaction with imidazole.
      Whereas the conventional method requires about 12-15 min for equilibrium to be
      reached, kinetic measurements can be made within a few seconds. The calibration
      graph was linear over the range 1-40 microgram ml-1 of clavulanic acid and the
      detection limit achieved was 0.3 microgram ml-1. The precision and selectivity of
      the method are reported. The results obtained by applying the proposed method to
      the analysis of pharmaceutical and serum samples show how easily it can be
      adapted for routine analyses.

PMID- 8305598
TI  - Flow-injection spectrophotometric determination of piroxicam.
AB  - Two flow-injection analysis (FIA) methods are proposed for the determination of
      piroxicam. The first involves measurement of the UV absorbance of a solution
      containing the drug, methanol and hydrochloric acid at 332 nm; in the second
      method a Fe(III)-piroxicam complex is formed in a methanolic medium and the
      absorbance is measured at 520 nm. In both methods, the peak height is used as a
      quantitative parameter and piroxicam is determined over the ranges 0.5-15 and 30
      500 microgram ml-1, respectively. The methods have been applied to the routine
      determination of the drug in dosage forms.

PMID- 8305599
TI  - Phase-selective AC adsorptive stripping voltammetric assay for aminopterin and 10
      Edam in human serum.
AB  - Aminopterin was studied as a model compound for its analogues which maintain the
      pteridine ring in their structure. Its adsorptive behaviour on mercury was
      studied and the DC adsorptive stripping and phase-selective AC adsorptive
      stripping conditions were optimized. 10-Edam, an aminopterin analogue, was
      studied and shown to behave similarly to aminopterin. Phase-selective AC
      voltammetry provided the best signal and gave a detection limit of 4 x 10(-12) M
      aminopterin in aqueous solution employing an accumulation time of 10 min. The
      optimized method was applied to the analysis of both aminopterin and 10-Edam
      respectively in human serum. After extraction with a C18 reversed-phase cartridge
      the detection limit of the method was 1 x 10(-8) M aminopterin and the overall
      assay percentage recovery was 73.5% (n = 5) at a concentration of 5 x 10(-7) M
      aminopterin in serum. The analysis of 10-Edam at the same concentration in serum
      yielded the higher percentage recovery of 94.46% (n = 5) following the same
      procedure.

PMID- 8305600
TI  - Determination of dolasetron and its reduced metabolite in human plasma by GC-MS
      and LC.
AB  - Both a GC-MS and an LC method have been developed for the simultaneous
      quantitation of dolasetron and reduced dolasetron in human plasma. The GC-MS
      method has been utilized in preliminary human pharmacokinetic studies of
      dolasetron mesylate. Selected ion monitoring was used in these initial studies to
      obtain the sensitivity and specificity required for quantitation. The GC-MS
      method has been used in the range of 1-120 ng ml-1 for dolasetron and 1-240 ng ml
      1 for reduced dolasetron in plasma. The limit of quantitation for both compounds
      by GC-MS was 1 ng ml-1. Recently, an LC method has been utilized for quantitation
      of both compounds on a routine basis. This method utilizes essentially the same
      sample preparation procedure as the GC-MS method. The LC method has been used in
      the range of 5-200 ng ml-1 in plasma for dolasetron and reduced dolasetron. In
      addition, the relationship between the LC and GC-MS methods has been assessed
      using data obtained from human male volunteers following intravenous
      administration of 3.0 mg kg-1 of dolasetron mesylate monohydrate.

PMID- 8305601
TI  - Determination of cysteamine and cystamine by gas chromatography with flame
      photometric detection.
AB  - A gas chromatographic method for the determination of cysteamine and its
      disulphide cystamine is described. Cysteamine and cystamine are converted into
      N,S-diisobutoxycarbonyl and N,N-diisobutoxycarbonyl derivatives, respectively.
      The derivatives are analysed by gas chromatography with flame photometric
      detection, using a DB-210 capillary column. The calibration curves for cysteamine
      and cystamine in the range of 0.2-5.0 nmol are linear and sufficiently
      reproducible for quantitative analysis, and the detection limit is about 0.5 pmol
      injected. Cysteamine in mouse tissues is found in the free reduced, free oxidized
      and protein-bound forms. Free oxidized and protein-bound forms are reduced to
      free cysteamine by the use of sodium borohydride, and then derivatized.
      Cysteamine and cystamine in mouse tissues can be measured without any
      interference from coexisting substances by this method. The recoveries of
      cysteamine and cystamine added to the tissue samples are 91-106%, and their
      reproducibilities are found to be satisfactory. Analytical results for the
      determination of various forms of cysteamine in mouse tissues are presented.

PMID- 8305602
TI  - Separation of tetracyclines by liquid chromatography with acidic mobile phases
      and polymeric columns.
AB  - The LC separation of selected tetracyclines has been studied using polymeric
      columns. Mobile phases containing acetonitrile-0.02 M sodium perchlorate, pH 2.0,
      were used. Asymmetry factor and number of theoretical plates were calculated for
      the tetracyclines investigated on four polymeric columns. The columns included:
      two polystyrene-divinylbenzene (PS-DVB) copolymeric columns, a PS-DVB column with
      octadecyl ligands and a polymethacrylate column with octadecyl ligands (PM-C18).
      The PLRP-S (PS-DVB) column and the PM-C18 column were found to be the most
      suitable for the analysis of the selected tetracyclines. Resolutions between
      pairs of selected tetracyclines were calculated and compared for the latter two
      columns, with the PLRP-S (PS-DVB) columns showing the best results. The PM-C18
      column has the advantage of allowing the use of higher flow rates, which
      minimized analysis times. The tetracyclines included minocycline,
      oxytetracycline, tetracycline, demeclocycline, chlortetracycline, methacycline,
      doxycycline and meclocycline. Representative degradation products and impurities
      for selected tetracyclines were also included.

PMID- 8305603
TI  - Ion-exchange liquid chromatographic analysis of bisphosphonates in pharmaceutical
      preparations.
AB  - A simple, fast and uniform method has been developed for the quantitative
      determination of bisphosphonates in the quality control of pharmaceutical
      preparations. The method is based on ion-exchange liquid chromatography with
      conductivity detection. Separation is performed on a Waters IC-PAK Anion column
      using 2 mM nitric acid or 25 mM succinic acid as the mobile phase. Retention of
      the bisphosphonates can be influenced by pH and the anion concentration of the
      mobile phase. Sensitivity and selectivity are sufficient for the assay of
      bisphosphonates in bulk drug and pharmaceutical preparations. Sample preparation
      comprises dissolution or dilution of the sample in the mobile phase followed, if
      necessary, by filtration prior to HPLC analysis. Since the method is stability
      indicating, it is also well suited for shelf-life studies of bisphosphonate
      pharmaceutical preparations. Validation of the analytical method for the assay of
      pamidronate injection indicated an intra-day reproducibility of 1.7% (n = 6) and
      an inter-day reproducibility of 2.7% (n = 6). A linear relationship between
      response and concentration was found in the concentration range studied from 200
      ng to 10 micrograms pamidronate per 20 microliters injected. The lower limit of
      detection (signal-to-noise ratio = 3) of pamidronate was about 100 ng.

PMID- 8305604
TI  - An LC method for measuring complex formation equilibria by competitive chelation.
AB  - A method, entailing the use of a competitor ligand, is described for measuring
      complex formation constants by HPLC. The log of the formation constant of Gd(III)
      2,6-bis(aminomethyl)pyridinetetraacetate was determined to be 18.6, a previously
      unreported value.

PMID- 8305605
TI  - High-performance liquid chromatographic determination of nalidixic acid in rat
      serum, brain and cerebrospinal fluid.
AB  - A high-performance liquid chromatographic method for the determination of
      nalidixic acid (NA) in rat serum, brain and cerebrospinal fluid (CSF) was
      developed. NA in rat serum and brain homogenate was extracted and injected onto a
      reversed-phase column. CSF was directly analysed without extraction procedure.
      The limits of detection were 0.05 microgram ml-1 for serum, 0.07 microgram g-1
      for brain and 0.02 microgram ml-1 for CSF, respectively. Calibration curves were
      linear over the concentration ranges 0.1-50 micrograms ml-1 for serum, 0.12-9
      micrograms g-1 for brain and 0.05-10 micrograms ml-1 for CSF, respectively. The
      reproducibility of NA assay in rat biological media ranged from 1 to 4% relative
      standard deviations (RSD). The recoveries of NA added to serum and brain were
      higher than 96% with an RSD of less than 4%. The present method was found to be
      applicable to pharmacokinetic study of NA in rat serum, brain and CSF.

PMID- 8305606
TI  - Determination of peptide 520 in human plasma using post-column photolysis with
      electrochemical detection in liquid chromatography.
AB  - A simple LC method for the determination of peptide 520 in human plasma was
      developed. Based on micellar chromatography, sodium octyl sulphate (SOS) was
      added into the mobile phase in order to separate the peptide from human plasma
      components. The procedure was fast and sensitive for the determination of the
      peptide in untreated human plasma. The electrochemical (EC) detection limit for
      peptide 520 in human plasma was 0.5 microgram ml-1. Linearity of the calibration
      plot for peptide 520 in human plasma was 0.999. This approach represents a direct
      injection technique for the potential detection and analysis of numerous peptides
      in biofluids, besides just plasma, with absolute quantification.

PMID- 8305607
TI  - Orthodontic considerations in selecting wind instruments.

PMID- 8305608
TI  - Correcting anterior crossbites in the deciduous dentition of the young child:
      another technique.

PMID- 8305609
TI  - Case report: adult skeletal Class III.

PMID- 8305610
TI  - Begin with the end in mind.

PMID- 8305611
TI  - Retreating orthodontic failures: Part I.
AB  - This article presents a number of cases originally treated by orthodontic
      specialists which were retreated because the initial results became unstable over
      time. Diagnostic evaluations uncovered many common reasons for the initial
      treatment failures. Methods utilized during re-treatment addressed the causative
      factors related to the initial instability and have proven effective in
      maintaining a consistent dental relationship for over five years. The results
      have been both aesthetic and functional.

PMID- 8305612
TI  - A new fixed mandibular expansion appliance for uncrowding incisors during early
      mixed dentition.

PMID- 8305613
TI  - Case report: Class III, crowded.

PMID- 8305614
TI  - Retreating orthodontic failures: Part II.
AB  - Part I of this series (June 1993 JGO) clearly documented the inadequacies of some
      orthodontic methods to obtain satisfactory stable results for patients. Forty
      four patients were selected for this study, as their prior orthodontic treatments
      -all from orthodontic specialists or orthodontic postgraduate institutions--had
      failed for a variety of functional reasons. The treatment for the 44 patients
      would not have been necessary if the initial orthodontic treatment had been
      successful. Therefore, somewhere in the treatment, problems existed which were
      not corrected by the treatment methods, or problems arose because of the
      treatment methods. Part I of this series clearly and precisely showed that some
      orthodontic methods initiate TMJ problems. In a review of the literature
      presented in Part I, the following conclusions were reached: 1. The optimum
      functional relationship of the human temporomandibular joint exists when the
      force vectors within the joint are directed anteriorly and superiorly. 2. Some
      orthodontic treatments disrupt this optimum functional relationship by placing
      posterior or posterior/superior forces on the structures of the temporomandibular
      joint. 3. There is an increased incidence of joint signs and symptoms for some of
      the patients treated with those conventional methods which place pathologic
      forces on the temporomandibular joints. Present treatment methods are inadequate
      if they damage the patient's structures. The guidelines of treatment are wrong if
      problems exist because of the treatment methods and these guidelines then need to
      be corrected. What is offered in this article is a method of treatment that was
      and is successful in retreating those patients who were initially treated by
      orthodontic specialists, yet who developed TMJD problems during or after their
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305615
TI  - The mass concentrations of serum troponin T and creatine kinase-MB are elevated
      before creatine kinase and creatine kinase-MB activities in acute myocardial
      infarction.
AB  - The time-related frequency of elevated results for the mass concentrations of the
      MB isoenzyme of creatine kinase and of troponin T were compared with that of
      creatine kinase and creatine kinase-MB activity in patients with acute myocardial
      infarction. Patients (322; 175 with and 147 without myocardial infarction)
      consecutively admitted for evaluation of possible acute myocardial infarction
      were investigated. Reference limits for troponin T (0.1 microgram/l) and creatine
      kinase-MB mass concentration (5.0 micrograms/l) were exceeded frequently in
      patients with unstable angina pectoris (troponin T 43%, creatine kinase-MB mass
      concentration 24%) in contrast to patients with no acute ischaemic heart disease
      (both < 5%). Within 4 and between 4-8 hours after onset of chest pain, the
      frequency of elevated results for creatine kinase-MB mass concentration and
      troponin T in patients with acute myocardial infarction was considerably higher
      (20-30%) than for creatine kinase and creatine kinase-MB activity. Creatine
      kinase-MB mass concentration and troponin T both allowed earlier diagnosis of
      acute myocardial infarction than creatine kinase and creatine kinase-MB activity,
      but troponin T was not elevated before the creatine kinase-MB mass concentration.

PMID- 8305616
TI  - Oxidative modification of low density lipoproteins by human polymorphonuclear
      leukocytes.
AB  - Oxidatively modified low density lipoproteins are thought to play an important
      role in the generation of macrophage-derived foam cells in early atherosclerotic
      lesions. Cultured endothelial cells, monocytes, macrophages and smooth muscle
      cells can modify low density lipoproteins, either by a free radical mechanism or
      by the action of lipoxygenases. Previous studies demonstrated that activated
      human polymorphonuclear leukocytes can oxidize low density lipoprotein lipids.
      Stimulation of the cells with phorbol 12-myristate 13-acetate resulted in an
      increase both in superoxide anion production and in low density lipoprotein
      oxidation. The present results show that the oxidative modification of low
      density lipoproteins by human polymorphonuclear leukocytes can be inhibited by
      superoxide dismutase but not by the lipoxygenase inhibitor, (5,8,11,14)
      eicosatetraynoic acid. The low density lipoproteins oxidized by polymorphonuclear
      leukocytes were recognized by the scavenger receptor of macrophages (P 388 cell
      line). It is proposed that the superoxide anion is an important factor in the
      oxidative modification of low density lipoproteins induced by polymorphonuclear
      leukocytes, and that under conditions of increased oxidative metabolism in vivo,
      polymorphonuclear leukocytes can contribute to foam cell formation by a scavenger
      receptor-dependent process at lesion sites.

PMID- 8305617
TI  - Apolipoprotein E to B ratio: a marker for type III hyperlipoproteinaemia.
AB  - Apolipoproteins B and E were determined in 40 patients with type III
      hyperlipoproteinaemia (familial dysbetalipoproteinaemia) and in 48 patients with
      other types of hyperlipoproteinaemia matched for cholesterol and
      triacylglycerols. In type III patients, apolipoprotein E was increased and
      apolipoprotein B was lower than in other types of hyperlipoproteinaemia. The
      apolipoprotein E to apolipoprotein B ratio almost completely discriminated
      between type III and other types of hyperlipoproteinaemia. Assuming a cut-off
      value of 0.09 for the apolipoprotein E to apolipoprotein B ratio, diagnostic
      sensitivity was 95% and specificity was 88%. It is concluded that the
      apolipoprotein E to apolipoprotein B ratio represents the first-line screening
      quantity of choice for the identification of patients with type III
      hyperlipoproteinaemia in the clinical laboratory.

PMID- 8305618
TI  - Application of the time-resolved immunofluorometric assay to the study of C3
      complement component glycation in vitro and in vivo.
AB  - A time-resolved immunofluorometric assay (TR-IFMA) was used for the measurement
      of glycated C3. The very high sensitivity of this technique allowed the direct
      measurement of glycated and non-glycated proteins (especially C3) in
      chromatography eluates. C3 glycation in vitro after incubation with 20 mmol/l
      glucose was always less than 3.5% by day 5. As determined with the TR-IFMA, the
      means +/- standard deviations of glycated C3 were 0.20% +/- 0.04 for non-diabetic
      subjects and 0.88% +/- 0.06 for insulin-dependent diabetic patients. The low
      percentages of glycated C3 in both our in vitro and in vivo studies show that
      this protein is subject to only moderate rates of glycation.

PMID- 8305619
TI  - Interference of metamizol (dipyrone) on the determination of creatinine with the
      Kodak dry chemistry slide comparison with the enzymatic method from Boehringer.
AB  - In order to eliminate positive interferences that take place with the Jaffe
      technique, the Kodak Ektachem and Boehringer Mannheim Companies have chosen an
      enzymatic method for the determination of creatinine in serum and urine.
      Pathological and clinical samples often contain metabolites in elevated
      concentrations or exogenous compounds such as drugs or toxic compounds. We
      noticed that patients receiving metamizol-containing drugs showed unusually low
      values of creatinine when determined with an Ektachem analyser. We investigated
      the effect of the main metabolites of this prodrug on the creatinine enzymatic
      methods of Kodak and Boehringer. We concluded that methyl-amino-antipyrine, the
      active substance after administration of metamizol (prop. INN) was responsible
      for the interference, and that no reliable determination of creatinine could be
      performed with these methods in the serum of patients receiving this drug.

PMID- 8305620
TI  - Studies on the concentration of arsenic, selenium, copper, zinc and iron in the
      blood of blackfoot disease patients in different clinical stages.
AB  - Flame atomic absorption spectrophotometric methods were developed for the
      determination of zinc, copper, arsenic, iron and selenium in blood samples. Data
      from blackfoot disease patients in five clinical stages were compared with those
      from healthy controls. Copper concentrations were the same for all clinical
      stages. Arsenic increased in the initial three stages but decreased thereafter,
      although arsenic was previously considered to be the major causative agent of the
      disease. The decrease of arsenic in the later stages was attributed to the
      antagonistic effect of selenium, and the decrease of iron during the progress of
      the disease is thought to be due to the antagonistic effect of arsenic in the
      initial stages and the loose of haemoglobin in the later stages.

PMID- 8305621
TI  - Blood plasma pseudouridine in patients with malignant proliferative diseases.
AB  - The blood plasma concentration of pseudouridine was estimated in 104 healthy
      adult subjects, and 108 patients suffering from malignant proliferative diseases.
      The HPLC method for simultaneous determination of pseudouridine and creatinine
      was applied. The average physiological concentration of pseudouridine in blood
      plasma was 2.43 +/- 0.97 mumol.l-1 or 29.15 +/- 7.40 mmol.mol-1 creatinine. The
      physiological urinary excretion of pseudouridine was 14.32 +/- 5.20 mumol.24 h
      1.kg-0.75 or 19.60 +/- 5.22 mmol.mol-1 creatinine. Renal clearance of
      pseudouridine and endogenous creatinine were 4.04 +/- 0.99 and 5.50 +/- 1.46
      ml.kg-0.75, respectively. A positive correlation (r = 0.55, P < 0.01) was found
      between age (in the range 20-92 years) and blood plasma pseudouridine
      concentration (mumol.l-1). By expressing plasma pseudouridine in relation to
      plasma creatinine, the apparent influence of non-metabolic factors (age, renal
      insufficiency, blood dilution) on the plasma pseudouridine concentration were
      largely excluded. Among haematological proliferative diseases the highest values
      of plasma pseudouridine concentrations were observed in chronic lymphocytic
      leukaemia (8.19 mumol.l-1; 54.9 mmol.mol-1 creatinine) and multiple myeloma (7.02
      mumol.l-1; 52.5 mmol.mol-1 creatinine). In multiple myeloma, but not in chronic
      lymphocytic leukaemia, the plasma pseudouridine concentration depended on the
      clinical stage. A lower, but still significant response in non-Hodgkin's lymphoma
      was noted (4.03 mumol.l-1; 40.88 mmol.mol-1 creatinine). A significant increase
      of the plasma pseudouridine concentration was characteristic of adenocarcinomas
      of the large intestine, and it occurred in the early stages of malignant growth.
      In patients with lung cancer the plasma pseudouridine concentration was elevated
      only in advanced cases with metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305622
TI  - Effect of different columns and internal standards on the quality assurance of
      the gas chromatographic determination of blood ethanol.
AB  - Quality assurance is an essential requirement of clinical and forensic
      laboratories, especially in the determination of ethanol. Opinions differ as to
      whether normal gas chromatographic methods should be used with modified
      procedures, or whether different chromatographic strategies should be adopted,
      the choice being based entirely on practical considerations. We have evaluated
      the influence on the blood ethanol determination of the frequently used glass and
      steel columns, as well as the use of isopropanol and tert-butanol as internal
      standards. All the different combinations of column type and standard provided
      accurate and reliable results with no significant deviation. Standardization of
      the analytical procedure is therefore unnecessary, but international ethanol
      standards should be analysed sequentially to test the method and the staff
      performing the analyses in the different laboratories.

PMID- 8305623
TI  - The performance of the Chem-1 revisited: an evaluation after 3 years.
AB  - An evaluation of the Bayer-Technicon Chem-1 multitest analyzer is described over
      the period 1989-1992. Various aspects like daily use, running costs and quality
      assessment are discussed. The whole process regarding the performance, ranging
      from negative feelings in the first year to satisfaction in the third, is
      followed critically.

PMID- 8305624
TI  - Serum alkaline deoxyribonuclease activity, a sensitive marker for the therapeutic
      monitoring of cancer patients: methodological aspects.
AB  - Alkaline deoxyribonuclease (DNase) is present in human circulating serum but its
      physiological role and signification of its variations are still largely unknown.
      The present report demonstrates that between 37 degrees C and 50 degrees C, as
      measured in the presence of 0.25 mmol/l Ca2+ and 5 mmol/l Mg2+, serum alkaline
      DNase activity increases, in most sera, reaching a level far higher than expected
      from thermal activation. This observation is thought to be due to the thermal
      inactivation of a serum inhibitor of the enzyme, which limits its usefulness as a
      therapeutic marker. By measuring serum alkaline DNase activity at 50 degrees C,
      the authors have developed a clinical test which has been successfully applied to
      the therapeutic monitoring of patients with various types of cancers.

PMID- 8305625
TI  - Pitfalls in the quality assessment of iron determinations.

PMID- 8305626
TI  - Towards a standardized clinical laboratory report in the European Community.

PMID- 8305627
TI  - An estimate of the rate of direct drug diffusion from the surface of heart and
      kidney--implications for their representation as compartments.
AB  - In many regional pharmacokinetic experiments and models, the anatomical
      boundaries of the heart and kidney are intrinsically assumed to be barriers for
      drug diffusion such that these organs can be represented as one or more
      compartments. To test this, an experimental preparation was developed in which
      the heart and kidney of anaesthetized sheep were surrounded with 0.9% saline. The
      rate of drug diffusion from the surface of the organs into the saline was
      examined during constant-rate i.v. drug infusions. It was found that the maximum
      clearances of lidocaine and procainamide into the pericardial saline were 10.3
      11.6 and 0.6-2.1 ml min-1 respectively, and the values for the kidney were 0.3
      0.6, 0.1-1.0 and 0.4-1.3 ml min-1, for lidocaine, procainamide, and meperidine
      respectively. These corresponded to calculated times of 4-481 min to reach the
      steady-state saline concentration depending on the drug and the organ. The steady
      state ratio of the saline concentrations over the arterial blood drug
      concentrations usually ranged from 0.5-1.0. It is concluded that drugs can
      rapidly enter regions of low or no perfusion surrounding these organs, and that
      the concept of treating the heart and kidney as compartments may not be valid in
      certain 'worst-case' situations.

PMID- 8305628
TI  - Pharmacokinetics of anticholinergic drugs and brain muscarinic receptor
      alterations in streptozotocin diabetic rats.
AB  - We studied the effects of experimental diabetes on the pharmacokinetics of
      biperiden (BP) and scopolamine (SP) and brain muscarinic receptor alterations in
      rats after the injection of streptozotocin (STZ) (60 mg kg-1 i.v.). The serum
      levels of BP and SP differed significantly between the rats 14 weeks after the
      STZ treatment and age-matched control rats. The values of total body clearance
      (CLtot) of BP and SP were significantly increased by STZ treatment. The values of
      volume of distribution (Vdss) of SP were slightly increased in the STZ-treated
      rats, although Vdss of BP was decreased. Because of the high lipophilicity of BP,
      Vdss of BP may be decreased due to the reduced fat tissue volume caused by STZ
      treatment. The density of the muscarinic receptors in whole brain was measured by
      a radioligand receptor binding assay using [3H]-quinuclidinyl-benzylate ([3H]
      QNB). The density in the diabetic rats two weeks after the STZ treatment was
      significantly decreased compared to age-matched control rats. However in the
      diabetic rats 14 weeks after the STZ treatment, there was no difference in the
      density of muscarinic receptors. The IC50 of muscarinic antagonist for the
      binding of [3H]-QNB to the receptor did not change on STZ treatment. Modulation
      of the receptor following repeated anticholinergic drug exposure was studied. In
      control rats, the number of muscarinic receptors in the brain increased by 6.9%
      on chronic treatment with BP for two weeks. When diabetic rats were treated with
      BP and SP, the number of muscarinic receptors in the brain increased by 9.6% and
      33.8%, respectively.

PMID- 8305629
TI  - Comparison of a new orally potent tripeptide HIV-1 protease inhibitor (anti-AIDS
      drug) based on pharmacokinetic characteristics in rats after intravenous and
      intraduodenal administrations.
AB  - Recently, a series of KNI compounds such as KNI-227 and KNI-272 has been
      synthesized and shows potent and selective HIV-1 protease inhibitory activity in
      vitro. In this study, we developed an HPLC assay system for KNI-227 and KNI-272
      in rat plasma and examined the pharmacokinetic characteristics in rats after both
      intravenous (i.v.) and intraduodenal (i.d.) administrations to obtain the
      disposition characteristics and bioavailabilities of these new anti-AIDS drugs.
      After i.v. administration of KNI-227, 10.0 mg kg-1, the mean terminal elimination
      half-life, t1/2 lambda zeta, was 0.808 +/- 0.161(SE) h, the total body clearance,
      CLtot, was 11.7 +/- 3.3 ml min-1 and the distribution volume at steady state
      (Vd,ss) was 1410 +/- 460 ml kg-1. On the other hand, after i.v. administration of
      KNI-272, 10.0 mg kg-1, t1/2 lambda zeta was 2.86 +/- 0.78 h, CLtot was 15.3 +/-
      1.4 ml min-1 and Vd,ss was 3440 +/- 670 ml kg-1. In the case of the i.d.
      administration of drugs, the mean peak plasma concentrations, Cmax, of KNI-227
      and KNI-272 were 0.374 +/- 0.110 microgram ml-1 and 0.900 +/- 0.093 micrograms ml
      1, respectively. The bioavailabilities (BA) of KNI-227 and KNI-272 to infinity,
      BA(0-infinity), were 5.90% and 42.3%, respectively. As compared with the lead
      compound, KNI-174, the BA of KNI-272 was improved about 10 times. Although the
      anti-AIDS virus activity of these two drugs has not been investigated in vivo,
      KNI-272 is expected to be a better candidate for oral anti-AIDS therapies.

PMID- 8305630
TI  - Biotransformation and urinary excretion of 4-substituted amphetamines in pregnant
      mice.
AB  - The urinary elimination of 4-hydroxyamphetamine (PHA) and a series of homologous
      4-alkoxy-substituted amphetamines and their metabolites was examined after single
      and multiple oral administration to pregnant and non-pregnant mice. The metabolic
      profile and extent of biotransformation in a series of alkoxy analogues were
      affected by the size of the alkoxy side chain, multiple dosing and pregnancy.
      There were increased recoveries of both the substrate and the conjugated
      derivative of PHA during gestation. The major metabolic routes observed were O
      dealkylation, conjugation, and aliphatic hydroxylation of the propoxy side chain.
      There was some evidence of oxidative deamination. Pregnancy did not alter the
      profile of the major metabolites detected by GLC and NMR spectroscopy.

PMID- 8305631
TI  - A glance back over 30 years.

PMID- 8305632
TI  - The history of proton-driven ATP formation.
AB  - This article sets down the beginnings of some thoughts in bio-energetics. It
      illustrates how difficult it is in science as elsewhere to know how a new idea is
      generated. The literature needs very careful examination and separation from
      personalities.

PMID- 8305633
TI  - Characterization of specific calcitonin gene-related peptide receptors present in
      hamster pancreatic beta cells.
AB  - Calcitonin gene-related peptide (CGRP) shares about 46% and 20% amino acid
      sequence homology with islet amyloid polypeptide (IAPP) and salmon calcitonin
      (sCT). We investigated whether these related peptides could cross-react with the
      specific binding of 125I-[His]hCGRP I to the CGRP receptor in hamster insulinoma
      cell membranes. A rapid dissociation of membrane bound 125I-[His]hCGRP I could be
      induced in the presence of 1 microM chicken CGRP (cCGRP). The specific 125I
      [His]hCGRP I binding was inhibited by the related peptides and their half-maximal
      inhibitory concentrations (IC50) were: cCGRP (0.1 nM), rat CGRP I and human CGRP
      I and II (1.0-2.0 nM), fragment of hCGRP I (8-37) (150 nM), human IAPP (440 nM).
      The non-amidated form of hIAPP; human diabetes-associated peptide (hDAP) did not
      inhibit the binding of 125I-[His]hCGRP I and sCT was only effective at a high
      concentration (1 microM). Binding of 125I-[His]hCGRP I was dose dependently
      inhibited by guanosine-5'-O-(3-thiotriphosphate) or (GTP gamma S) and a 70%
      reduction of binding was obtained with 0.1 mM GTP gamma S. The IC50 value of
      cCGRP (0.1 nM) was increased 100-fold in the presence of 0.1 mM GTP gamma S.
      Human CGRP I and cCGRP at 2.5 microM did not stimulate the activity of hamster
      insulinoma cell membranes adenylate cyclase, while glucagon (1 microM) induced a
      2-fold increase. Thus, specific CGRP receptors present in hamster beta cells are
      associated with G protein (s) and IAPP can interact with these receptors. These
      results and the observation that cCGRP and hCGRP I did not influence adenylate
      cyclase activity provide further evidence for CGRP receptor subtypes.

PMID- 8305634
TI  - Interaction of sporidesmin, a mycotoxin from Pithomyces chartarum, with lipid
      bilayers.
AB  - Sporidesmin, a mycotoxin from Pithomyces chartarum is a hydrophobic molecule. It
      can therefore be easily incorporated in the cell membrane, where it is likely to
      cause changes in the bilayer organization and the properties of membrane
      proteins. In order to understand the redox behaviour of sporidesmin in a
      hydrophobic environment, we have investigated the effects of oxidized and reduced
      sporidesmin on the phase transition properties of bilayers and on the
      susceptibility of bilayers to pancreatic phospholipase A2 (PLA2). The changes
      induced by sporidesmin in the thermotropic phase transition profiles of
      dimyristoyl-sn-3-phosphatidyl choline (DMPC) bilayers were similar to those
      caused by solutes known to localize in the glycerol-backbone region of the lipid
      bilayer, suggesting a similar localization for oxidized and reduced sporidesmin.
      Neither form of toxin disrupt the bilayer or membrane organization even at
      relatively high mole fractions. At concentrations < 10 mole% both forms
      partitioned equally well in the gel and liquid-crystalline phases, whereas at
      higher concentrations (approximately 30 mole%) reduced sporidesmin is
      preferentially localized in the liquid-crystalline phase. These effects of
      sporidesmin on the phase properties of DMPC vesicles were also reported by the
      fluorescence behavior of 10-pyrenedecanoic acid (PDA). The effects of oxidized
      and reduced sporidesmins on PLA2 kinetics are consistent with their ability to
      perturb bilayer organisation.

PMID- 8305635
TI  - Delta-toxin, unlike melittin, has only hemolytic activity and no antimicrobial
      activity: rationalization of this specific biological activity.
AB  - The antimicrobial activity of a synthetic peptide corresponding to delta
      hemolysin had been examined. The peptide did not exhibit antimicrobial activity
      against gram negative and gram positive micro-organisms unlike other hemolytic
      peptides like melittin. This lack of antibacterial activity arises due to the
      inability of delta-hemolysin to perturb the negatively charged bacterial cell
      surface and permeabilize the bacterial plasma membrane. However, the red blood
      cell surface has a structure considerably different from bacteria and does not
      act as a barrier to molecules reaching the lipid membrane. Hence delta-toxin can
      lyse erythrocytes. Thus, the specificity in biological activity has been
      rationalized in terms of differences in the interaction of the toxin with the
      bacterial and red blood cell surfaces.

PMID- 8305636
TI  - Is the process of urinary urea concentration responsible for a high glomerular
      filtration rate?
AB  - For subjects on a normal diet, urea is the major urinary solute and is markedly
      concentrated in the urine compared with in the plasma. Because urea is not known
      to undergo active secretion, its excretion rests on filtration lessened to a
      variable extent by tubular reabsorption. It is well established that the
      efficiency of urea excretion drops with increasing urinary concentration and
      decreasing urinary flow rate (from approximately 60% of filtered load, above 2
      mL/min, to approximately 20% below 0.5 mL/min) because the prolonged transit time
      in the distal nephron favors passive urea reabsorption. Thus, a higher urinary
      concentration is achieved at the expense of a reduced efficiency of urea
      excretion. Recent experimental observations suggest that GFR could actually
      increase in parallel with the urinary concentrating activity, thus ensuring a
      normal urea excretion in the face of a high, concentration-dependent urea
      reabsorption, with only a moderate increase in plasma urea. A possible mechanism
      is proposed that could explain how the vasopressin-induced intrarenal recycling
      of urea (which contributes to improvement in urinary concentration), but not an
      exogenous urea administration, could indirectly depress the tubuloglomerular
      feedback and hence increase GFR. An increased concentration of an osmotically
      active solute in the thick ascending limb of Henle's loop (such as urea and, in
      some cases, glucose) could enable a lower NaCl concentration to be achieved at
      the macula densa by reducing the osmotically driven water leakage in this nephron
      segment. This mechanism could explain the hyperfiltration seen in various
      pathophysiologic situations such as chronic vasopressin infusion, high protein
      intake, severe burns, and diabetes mellitus. Whatever the mechanism, if the need
      to excrete relatively high amounts of urea in a concentrated urine leads to a
      sustained elevation of GFR, the price to pay for this water economy is higher
      than generally assumed. It is not limited to the energy spent in the sodium
      reabsorption providing the "single effect" for the urinary concentrating process.
      It also includes the consequences on the glomerular filter of sustained high
      pressure and flow and the energy spent in reabsorbing the extra load of solutes
      filtered. In chronic renal failure, the ability to form hypertonic urine declines
      but is nevertheless well preserved with respect to declining GFR, thus imposing
      on remnant nephrons an additional permanent stimulus for
      hyperfiltration.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8305637
TI  - Regulation and properties of extracellular signal-regulated protein kinases 1, 2,
      and 3.
AB  - The extracellular signal-regulated kinases ERK1 and ERK2 are 43- and 41-kd
      enzymes activated by many extracellular cues. They lie within a protein kinase
      cascade that is used to achieve many cellular responses. In addition to the wide
      variety of regulatory contexts in which they are activated, they phosphorylate
      important regulatory proteins, including receptors, transcription factors,
      cytoskeletal proteins, and other protein kinases. Thus, the stimulation of this
      kinase cascade is thought to have a pleiotropic action. ERK1 and ERK2 are
      controlled by phosphorylation on threonine and tyrosine. To understand the
      regulatory mechanisms, wild-type and mutant ERKs were expressed in bacteria and
      phosphorylated with MEK, the enzyme that is upstream of ERKs. Wild-type proteins
      could be activated 500- to 1,000-fold in vitro by MEK. ERK3, an enzyme of 62 kd
      and only 50% identical to ERK1 and ERK2 in the catalytic core, was also
      phosphorylated by MEK in vitro. This suggests that all three of these enzymes are
      targets of common signaling pathways.

PMID- 8305638
TI  - Obstructive sleep apnea and the kidney.
AB  - Recent studies of obstructive sleep apnea and its comorbidity with other systemic
      diseases have stimulated interest in the relationship of apnea to renal disease
      and hypertension. Polysomnographic sleep studies in patients on dialysis who
      complain of day-time fatigue or sleepiness reveal significant apnea in up to 73%
      of those studied. Abnormalities in respiratory controller mechanisms from chronic
      hypocarbia, metabolic acidosis, and uremic toxins have been blamed for the
      occurrence of apnea in this setting. Proteinuria and sometimes nephrotic syndrome
      have been recognized in morbidly obese patients with sleep apnea syndrome. Renal
      biopsies of such patients have shown glomerulomegaly and focal segmental
      sclerosis. It is postulated that these lesions may result from increased
      glomerular filtration and blood flow. Elevated urine output, sodium and chloride
      excretion, and atrial natriuretic peptide have been well demonstrated in
      obstructive apnea patients and correct to control levels with treatment of the
      apnea. Both acute (with each apnea) and chronic daytime blood pressure elevation
      are frequently observed in sleep apnea patients, and occult sleep apnea is
      postulated as one possible cause of "primary" hypertension in middle-aged men. In
      younger patients, such hypertension seems to be more reversible with the
      elimination of apnea. In older patients, however, the cure of systemic
      hypertension cannot be guaranteed with the elimination of the apnea, and
      asymptomatic apnea patients tend not to tolerate the bother and discomfort of
      apnea treatment with nasal continuous positive airway pressure. Therefore, aside
      from a careful history regarding sleep symptomatology, polysomnographic studies
      of clinic populations with primary hypertension to search for apnea as a cause
      cannot be recommended.

PMID- 8305639
TI  - Immune hemolytic anemia after renal transplantation secondary to ABO-minor
      mismatch between the donor and recipient.
AB  - A 52-yr-old man developed immune hemolytic anemia approximately 2 wk after
      receiving an ABO-minor-mismatch renal transplant. When a Group O organ is
      transplanted into a non-O recipient or a non-AB organ is transplanted into a
      Group AB recipient, hemolysis can occur and has been attributed to a form of
      graft-versus-host disease in which donor plasma cells carried along with the
      graft produce red blood cell antibodies. In this case, the diagnosis was
      confirmed when an antibody screen indicated that the organ recipient's serum
      agglutinated panel red blood cells of the recipient's ABO group. This type of
      hemolysis usually occurs 1 to 2 wk after transplantation, is limited in duration,
      and can be severe. If transfusion is required, blood of donor type should be
      used.

PMID- 8305640
TI  - Effect of low-dose aspirin on thromboxane production and the antihypertensive
      effect of captopril.
AB  - Some of the antihypertensive effects of angiotensin-converting enzyme (ACE)
      inhibitors occur through nonangiotensin II-mediated mechanisms. One of these is
      through decreased kinin degradation, leading to enhanced production of
      vasodilator arachidonic acid metabolites. It was reasoned that if ACE inhibition
      also leads to an increase in the production of the potent vasoconstrictor
      thromboxane A2, then maneuvers that selectively inhibit thromboxane production
      without reducing prostaglandins (PG) E2 + PGI2 might enhance the antihypertensive
      effect of ACE inhibition. This double-blinded, randomized, crossover study was
      therefore undertaken to determine: (1) if captopril increases platelet and/or
      renal thromboxane production; and (2) if low-dose aspirin enhances the
      antihypertensive effect of captopril. Patients with mild essential hypertension
      and no other significant medical problems were studied. In a double-blinded,
      random order, patients took captopril alone (25 mg every 12 h) for 2 wk and
      captopril plus aspirin (75 mg/day) for another 2 wk. Active treatment periods
      were preceded by 2 wk of single-blind placebo. Fifteen patients with a mean age
      of 53 yr and an average mean arterial pressure (MAP) of 114 +/- 8 (+/- SD) mm Hg
      were studied. Serum thromboxane B2 was higher (P < 0.05) during treatment with
      captopril/placebo (600 +/- 46 (+/- SE) pg/mL) than during the two washout periods
      combined (420 +/- 57 and 553 +/- 78) and was lowest (P < 0.0005) during treatment
      with captopril/aspirin (302 +/- 36). Captopril treatment significantly increased
      the urinary excretion of PGE2 (P = 0.038). Captopril/placebo significantly
      lowered MAP (P < 0.05) to 105.0 +/- 3.7 mm Hg compared with the washout period.
      However, the addition of aspirin to captopril caused no additional lowering of
      MAP (105.2 +/- 2.8 mm Hg). It was concluded that treatment with captopril does
      increase platelet thromboxane production. However, lowering platelet thromboxane
      with low doses of aspirin may not enhance the antihypertensive effect of
      captopril.

PMID- 8305641
TI  - Ly-6 in kidney is widely expressed on tubular epithelium and vascular endothelium
      and is up-regulated by interferon gamma.
AB  - Ly-6 is a multigene family of murine polymorphic cell membrane proteins that are
      glycosydlphosphatidylinositol anchored, widely expressed on lymphoid tissue, and
      homologous to the recently described human CD59. An unexpected feature of Ly-6 is
      its high level of expression in the kidney. This renal expression and its
      interferon (IFN)-gamma inducibility in murine strains expressing different Ly-6
      haplotypes were studied with monoclonal antibodies and cDNA probes that recognize
      Ly-6A/E and Ly-6C. Ly-6 expression was much more extensive in the kidney than in
      other parenchymal organs. Ly-6A.1/E.2 was extensively expressed on vascular
      endothelium and on tubular epithelium, particularly in the distal nephron.
      Pattern of expression differed between strains expressing A and E alleles. Ly-6C
      was not detected by monoclonal antibodies but was detected by oligonucleotide
      specific probes. Treatment with recombinant IFN-gamma or IFN-inducing agents
      increased Ly-6 expression markedly, particularly on the luminal aspect of the
      proximal tubular epithelium, where Ly-6A/E became prominent. This luminal
      expression is typical for glycosydlphosphatidylinositol-anchored proteins but
      contrasts with that of other molecules, such as major histocompatibility classes
      I and II, which are generally expressed on the basolateral surface of the tubular
      epithelium. Up-regulation occurred within 6 h of IFN-gamma treatment and returned
      to normal by 48 h. Similar up-regulation of Ly-6 was seen in murine lupus
      nephritis and in mercuric chloride nephropathy. The characteristics of renal Ly
      6, such as its IFN-gamma responsiveness, endothelial and tubular expression,
      polymorphism, strong antigenicity, and possible allelic regulation, make it a
      candidate to be a target molecule in alloresponses. The renal expression of Ly-6
      is similar to that of CD59 in the human kidney, supporting the suggestion that
      these proteins are closely related.

PMID- 8305643
TI  - Blood pressure changes during daytime sleep and comparison of daytime and
      nighttime sleep-related blood pressure changes in patients with chronic renal
      failure.
AB  - Blood pressure has a diurnal pattern primarily related to activity and sleep.
      Chronic renal failure patients may lack the normal nocturnal decline in blood
      pressure during sleep. In 33 subjects (14 with normal renal function and 19 with
      renal dysfunction), the relationship between depth of daytime sleep, as
      determined by electroencephalographic sleep phase, and change in mean arterial
      blood pressure (MAP) and heart rate measured oscillometrically, was correlated.
      In 15 chronic renal failure patients, the effect of daytime and nighttime sleep
      on MAP and heart rate was compared. The percent change in night asleep versus day
      awake MAP and heart rate was measured (with Space Labs ambulatory blood pressure
      monitors) and compared with the percent change in daytime sleep-related MAP and
      heart rate measured during a daytime sleep electroencephalographic study. During
      daytime sleep, MAP changes are not significantly different in the normal versus
      renal dysfunction groups. In the 33 study subjects, MAP declines progressively
      from the upright position to Phase 3/4 sleep (118 +/- 3.6 to 106 +/- 3.6 mm Hg).
      The largest decline occurs between the upright to recumbent position, before
      sleep. Heart rate declines moving from the upright to recumbent position, 76 +/-
      2.3 to 70 +/- 2.1 beats/min, but does not decline further with sleep. In 15
      chronic renal failure patients, heart rate (10.8 +/- 2.8%; P < 0.05), but not
      MAP, declines during nighttime sleep. Both MAP (7.7 +/- 3.3%) and heart rate (5.4
      +/- 1.9%) decline significantly during daytime sleep. The responses of MAP and
      heart rate to daytime and nighttime sleep were in opposite directions in 3 of 15
      subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305642
TI  - Glomerular filtration rate measurements in clinical trials. Modification of Diet
      in Renal Disease Study Group and the Diabetes Control and Complications Trial
      Research Group.
AB  - To assess the utility and precision of GFR measurements in multicenter trials,
      the test performance and variability of GFR were analyzed in 2,250 patients
      enrolled in 44 clinical centers participating in either the Modification of Diet
      in Renal Disease (MDRD) Study or the Diabetes Control and Complications Trial
      (DCCT). GRF was measured as the renal clearance of [125I]iothalamate after an sc
      injection without epinephrine. The studies used similar protocols for obtaining
      blood and urine, training clinical center staff, and processing specimens in
      central laboratories. The performance of GFR measurements, assessed from
      adherence to protocol and quality control analyses, was excellent. The
      variability among the four clearance periods (intratest coefficient of variation
      [CV]) was acceptable; the median intratest CV for GFR was 9.4% in the MDRD Study
      and 11.7% in the DCCT. The pattern of decline in serum counts was better
      approximated by an exponential rather than a linear relationship. The cause of
      the intratest variability in GFR measurements was explored by univariate and
      multivariate analysis. The intratest CV was highest at the extremes of GFR. Among
      patients with a high GFR (> 90 mL/min per 1.73 m2), most of whom were
      participants in the DCCT, the higher intratest GFR was due, in part, to a
      systematic decline in GFR during the test. Among patients with a very low GFR (<
      13 mL/min per 1.73 m2), technical difficulties in urine collections contributed
      substantially to the higher intratest CV. Other patient characteristics,
      including age, gender, weight, serum glucose, renal diagnosis, and use of
      diuretics, were not strongly correlated with the intratest CV. The precision of
      GFR measurements was assessed from the variability from measurement to
      measurement (interest CV). Among MDRD Study subjects, in whom two measurements of
      GFR were performed over a 3-month interval, the median interest CV was relatively
      low (6.3%) and was only weakly related to the intratest CV. Thus, GFR
      measurements are reasonably precise, even if the intratest CV is high. Given the
      relatively high intratest CV that is characteristic of GFR measurements, the
      estimate of GFR in an individual is more precise if multiple clearance periods,
      rather than a single period, are included. Similarly, the estimate of mean GFR
      for a population is also more precise if multiple clearance periods are included.
      In conclusion, by the use of standardized methods, an acceptable precision of GFR
      results can be obtained in multicenter trials. The same methods can be applied in
      clinical practice.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8305644
TI  - Prevalence of missed treatments and early sign-offs in hemodialysis patients.
AB  - Hemodialysis patients often do not complete their full amount of time on dialysis
      and at times miss their hemodialysis treatments completely. However, neither the
      magnitude nor the potential reasons for this problem are known. The prevalence of
      unauthorized absences from hemodialysis sessions (no shows) and both the
      prevalence and reasons for early terminations from hemodialysis sessions (early
      sign-offs) were prospectively studied at a large hemodialysis unit in the
      southeastern United States. This unit provided a total of 31,212 hemodialysis
      sessions in a 12-month period to an average of 231 patients. There was a total of
      2,108 early sign-offs (6.8 +/- 0.9%/mo) and 387 "no-shows" (1.2 +/- 0.2%/mo)
      during this 12-month period. The most common reasons for early sign-off were
      cramping (17.9%), followed by "feels bad or sick" (14.2%), personal business or
      errands (12.1%), lack of transportation later in the day (7.7%), and refusal to
      comply with the prescribed treatment time (6.4%). In sum, approximately 55% of
      early sign-offs were due to medically related problems, whereas most of the
      remainder occurred because of either personal obligations or noncompliance with
      the dialysis prescription. This information should be of value when designing
      programs intended to reduce the number of early sign-offs in hemodialysis
      patients.

PMID- 8305645
TI  - The efficacy number as a predictor of morbidity and mortality in peritoneal
      dialysis patients.
AB  - The efficacy number has been proposed as a predictor of clinical outcome in
      patients on chronic ambulatory peritoneal dialysis (CAPD). The usefulness of this
      parameter in a large group of CAPD patients was analyzed. Forty-five patients who
      have received chronic CAPD therapy for at least 1 yr were included in the study.
      The efficacy number was compared with outcome as defined by mortality and days of
      hospitalization. Other demographic and laboratory parameters, including gender;
      race; presence of diabetes; serum albumin, serum creatinine, and BUN levels; and
      measures of peritoneal transport, including dialysate-to-plasma creatinine and
      dialysate-to-plasma urea ratios, were also assessed for their role in predicting
      outcome. Laboratory values were obtained at the initiation of CAPD and at 12
      months after the start of CAPD. By univariate analysis, a low 12-month serum
      albumin level was the best predictor of mortality (P < 0.005), followed by a high
      12-month efficacy number (P < 0.05). After adjusting for age and the presence of
      diabetes, these two variables remained the best predictors of mortality (P < 0.08
      and < 0.09, respectively). A low initial serum albumin level was also a strong
      predictor of mortality (P < 0.09). By univariate analysis, the best predictor of
      hospitalization was a low serum albumin level obtained either initially or at 12
      months (P < 0.005 for both time periods). After adjusting for age and the
      presence of diabetes, the 12-month serum albumin level remained a significant
      predictor of hospitalization (P < 0.03), whereas efficacy number was not a strong
      predictor (P = 0.27).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305646
TI  - Sodium modeling ameliorates intradialytic and interdialytic symptoms in young
      hemodialysis patients.
AB  - Despite advances in the delivery of hemodialysis, significant dialytic morbidity
      persists. Sodium modeling in older adults has been shown to decrease some
      dialytic symptoms, but clear benefits in young patients without coexisting
      diabetes or advanced cardiovascular disease have not been shown. The effects of
      sodium modeling were evaluated in 16 adolescent and young adult hemodialysis
      patients (16 to 32 yr of age) treated with conventional hemodialysis for a median
      of 11.5 months. The 8-wk study was divided into four 2-wk blocks. During each
      block, one of three sodium programs or a constant (control) dialysate sodium of
      138 mEq/L was used. During each sodium program, the initial dialysate sodium of
      148 mEq/L was decreased by an exponential, linear, or step program to 138 mEq/L.
      Treatments with sodium modeling were significantly better than those with
      constant sodium dialysate. When all sodium programs were grouped and compared
      with constant dialysate sodium, the odds of improvement in dialytic cramps,
      headaches, and nausea were 1.8, 2.1, and 3.9, respectively (P < 0.05). Sodium
      modeling also significantly decreased the frequency of postdialysis hypotension
      and interdialytic fatigue, dizziness, and muscle cramping (P < 0.05). No
      differences were seen among the sodium protocols in the incidence of symptomatic
      hypotension, the amount of normal saline administered, the degree of hemo
      concentration during treatments, or the decrease in serum osmolality. There was
      no increase in pretreatment or posttreatment serum sodium concentrations,
      interdialytic thirst, weight gain, or hypertension. Sodium modeling dramatically
      decreases both intradialytic and interdialytic morbidity in young hemodialysis
      patients. There was no increase in adverse events associated with sodium
      modeling.

PMID- 8305647
TI  - Patient survival on PAN/AN69 membrane hemodialysis: a ten-year analysis.
AB  - Survival characteristics over a 10-yr period of 352 patients on hemodialysis (HD)
      with polyacrylonitrile membranes in a single center were retrospectively analyzed
      and compared with national data collected by the U.S. Renal Data System (USRDS).
      Only those patients who stayed on HD for longer than 3 months were included. Any
      outcome other than death was considered as lost to follow-up. The number of
      expected deaths in the entire patient population according to the USRDS data base
      was 203, whereas the observed actual rate was only 132, reaching high statistical
      significance. Several subgroups of patients, stratified on the basis of age and
      time on starting HD, diabetes mellitus as the cause of original renal disease,
      etc., also exhibited significantly better survival. HD with a biocompatible
      membrane, providing adequate removal of low- as well as "middle"-molecular-weight
      uremic toxins, may be one important explanation for improved survival.

PMID- 8305648
TI  - Second generation logarithmic estimates of single-pool variable volume Kt/V: an
      analysis of error.
AB  - The original formula proposed to estimate variable-volume single-pool (VVSP) Kt/V
      was Kt/V = -In(R - 0.008 * t - f * UF/W), where in the Kt/V range of 0.7 to 1.3,
      f = 1.0 (* denotes multiplication). This formula tends to overestimate Kt/V as
      the Kt/V increases above 1.3. Because higher Kt/V values are now commonly
      delivered, the validity of both the urea generation term (0.008 * f) and
      correction for UF/W were explored by solving VVSP equations for simulated
      hemodialysis situations, with Kt/V ranging from 0.6 to 2.6. The analysis led to
      the development of a second-generation formula, namely: Kt/V = -In(R - 0.008 * t)
      + (4-3.5 * R) * UF/W. The first and second generation formulas were then used to
      estimate the modeled VVSP Kt/V in 500 modeling sessions in which the Kt/V ranged
      widely from 0.7 to 2.1. An analysis of error showed that this second-generation
      formula eliminated the overestimation of Kt/V in the high ranges found with the
      first-generation formula. Also, total error (absolute value percent error + 2 SD)
      was reduced with the second-generation formula. These results led to the proposal
      of a new formula that can be used for a very wide range of delivered Kt/V.

PMID- 8305649
TI  - Phosphate kinetics during high-flux hemodialysis.
AB  - Phosphate clearance by polysulfone (PS) and cuprophane (CU) membranes and the
      relationship of peridialytic changes in serum phosphate with those of serum
      ionized calcium, parathyroid hormone (PTH), and insulin were studied in six
      stable patients undergoing chronic hemodialysis (HD). Dietary phosphate intake
      was 25.7 mmol/day, and total dose of elemental calcium was 3.2 g/day. Patients
      were dialyzed for 2 to 4 h, once with each membrane. Serum phosphate levels fell
      precipitously during the first hour of HD with both dialyzers, from 1.42 and 1.49
      mM to nadirs of 0.53 and 0.69 mM for PS and CU, respectively. Phosphate levels
      began to increase either late in HD or at the end of HD and, by 4 h post-HD, did
      not differ from predialysis values. Total mass transfer of phosphate was greater
      during the first hour (3.4 and 3.2 mmol for PS and CU, respectively) than during
      the remainder of HD (2.4 and 2.6 mmol/h). There were no significant differences
      in intradialytic serum phosphate changes, postdialytic phosphate rebound, or
      total phosphate removal between the two dialyzers. Ionized calcium increased by
      0.11 mM, and PTH was suppressed to 40 to 50% of baseline values during dialysis
      with either membrane. Although phosphate removal continued for the duration of
      dialysis, serum phosphate did not continue to decrease, either reaching an
      apparent steady state or beginning to rebound, even during dialysis. This
      suggests active phosphate mobilization from a pool other than the extracellular
      fluid and demonstrates the inadequacy of a one-compartment model to explain these
      data. Further, these data do not support the regulation of intradialytic
      phosphate mobilization by serum PTH or insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305650
TI  - Baseline characteristics in the Modification of Diet in Renal Disease Study.
AB  - The Modification of Diet in Renal Disease Study is randomized, multicenter,
      clinical trial designed to determine the effects of three levels of dietary
      control of protein and phosphorus and two levels of blood pressure control on the
      rate of decline of kidney function among persons with chronic renal disease.
      Study participants were assigned to one of two studies, Study A or Study B,
      depending on their GFR just before randomization. Within each study, participants
      were randomly allocated to one of two levels of blood pressure control and to one
      of two dietary interventions according to separate 2 x 2 factorial designs. A
      total of 840 men and women aged 18 to 70 were randomized. This report summarizes
      the demographic, biochemical, and clinical characteristics of the randomized
      participants at the time of entry into the trail, overviews the protocol and
      purposes of the baseline period before randomization, and evaluates the balance
      among the treatment intervention groups within Studies A and B at the time of
      randomization. Major indicators of renal function were found to be well balanced
      among the treatment groups. Selected baseline characteristics of participants in
      the Modification of Diet in Renal Disease Study are compared with those of other
      renal clinical trials and with those of new cases of treated ESRD reported in the
      United States Renal Data System.

PMID- 8305651
TI  - Preoperative evaluation of vascular patients: are the benefits worth the cost?

PMID- 8305652
TI  - Changing times for anesthesiologists.

PMID- 8305653
TI  - Current practice in the preoperative evaluation of patients undergoing major
      vascular surgery: a survey of cardiovascular anesthesiologists.
AB  - Various cardiovascular testing modalities have been proposed as a means of
      reducing perioperative risk in patients undergoing vascular surgery. It is
      currently unknown with what frequency and under what conditions these tests are
      used in clinical practice. In an attempt to determine the spectrum of current
      clinical practice, the authors surveyed anesthesiologists who attended the 1992
      Society of Cardiovascular Anesthesiologists Annual Meeting. A total of 77 of 100
      surveys were returned, representing 58 institutions in the United States: 26
      university hospitals, 29 private hospitals, 2 Veterans Administration hospitals,
      and 1 military hospital. The incidence of preoperative testing was not
      significantly different between private and university institutions, and ranged
      from a mean of 54% of patients undergoing lower extremity procedures to 73% of
      patients undergoing aortic surgery, with a wide disparity among institutions.
      Dipyridamole or exercise thallium imaging was the most common test used, and
      Holter monitoring was the least common. The testing led to revascularization in
      52% of university and 72% of private hospitals. Testing was thought to result in
      modification of perioperative monitoring in 85% of the institutions and in
      modification of other aspects of care in a significant percentage of
      institutions. In conclusion, in this random population, preoperative testing was
      reported to be used in a significant percentage of patients, and similar
      practices were found between university and private institutions. The practices
      at the individual institutions and types of tests ordered varied greatly, and
      suggest the need for further research to determine optimal preoperative
      strategies.

PMID- 8305654
TI  - Risk factors for mortality after failed coronary angioplasty: an anesthesia
      perspective.
AB  - Monitored anesthesia care (MAC) for percutaneous transluminal coronary
      angioplasty (PTCA), and anesthesia for emergent coronary artery bypass graft
      (CABG) surgery due to failed PTCA, have added relatively new challenges to the
      cardiac anesthesiologist in community practice. This study attempted to define
      easily identifiable preangioplasty and periangioplasty risk factors for mortality
      after failed PTCA. A total of 1,380 angioplasties performed in a single community
      hospital were retrospectively reviewed; 120 (8.7%) were attempted PTCAs requiring
      subsequent CABG during the same hospital stay. The 120 failures included 10
      surgical mortalities (8.3%); multivariate analysis revealed several significant
      differences between the mortality and survivor groups. Mortality tended to be
      higher in insulin-dependent diabetics (P = 0.003), females (P = 0.005), and
      patients 70 years or over (P = 0.043). Previous CABG, decreased left ventricular
      ejection fraction, and number of vessels with significant disease did not differ
      between the groups. Patients who died required more vasopressor agents (P =
      0.011) during PTCA and experienced cardiac arrests (P = 0.011) at significantly
      higher rates than survivors. Left system (left anterior descending or circumflex
      coronary artery) angioplasty, inability to pass the angioplasty guidewire, and
      antiarrhythmic drug use did not differ between groups. Data concerning
      endotracheal intubation in the catheterization laboratory and time from
      laboratory exit to initiation of cardiopulmonary bypass, while bivariately
      significant, were too sparse for multivariate analysis. The authors believe that
      several risk factors for postangioplasty surgical mortality are easily determined
      without access to diagnostic angiographic studies.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8305655
TI  - Use of the right-sided precordial lead V4R in the detection of intraoperative
      myocardial ischemia.
AB  - This study evaluated the benefit of additional electrocardiographic monitoring of
      the right precordial lead V4R for detection of ST segment changes during elective
      coronary artery bypass surgery in 210 patients. ST segment analysis was performed
      for leads I, II, CB5, and V4R. ST segment changes were noted in 60 patients. Of
      these, 32 had combined left-sided and right-sided coronary artery disease (group
      A), and 28 had only left-sided coronary artery disease on coronary angiography
      (group B). Lead sensitivity was estimated assuming that all ST segment changes
      were true positive responses. Sensitivity using a single lead was greatest for
      lead CB5 in the two groups (76% in group A and 78% in group B). Sensitivity for
      lead I was low in both groups (34% in group A and 26% in group B). Sensitivity
      for lead II was 63% in group A and 52% in group B, and sensitivity for lead V4R
      was 71% in group A but only 37% in group B. Combination of leads V4R and CB5
      increased sensitivity to 98% in group A. In group B, this lead combination had a
      sensitivity of 93%, but lead combinations I-CB5-V4R and II-CB5-V4R were more
      sensitive (97% and 100%, respectively). The monitoring of lead V4R allowed
      detection of 20% of ST segment changes in group A that would have passed
      undetected if only leads I, II, and CB5 were monitored. These results demonstrate
      the value of additional electrocardiographic monitoring of the right precordial
      lead V4R during coronary artery bypass grafting in patients with right-sided
      coronary artery disease.

PMID- 8305656
TI  - Cardiac troponin T: a new marker of myocardial tissue damage in bypass surgery.
AB  - The purpose of this study was to evaluate cardiac troponin T (TnT) in the
      diagnosis of minor perioperative myocardial tissue damage and small myocardial
      infarctions during aortocoronary bypass surgery. In 15 patients without enzymatic
      or electrocardiographic signs of perioperative myocardial ischemia (group 1,
      uncomplicated bypass surgery), TnT did not exceed 3.55 micrograms/L. In 3
      patients with perioperative non-Q-wave infarctions (group 2), TnT was
      significantly higher than in group 1 patients. In all 3 patients, TnT peak
      concentrations exceeded 3.5 micrograms/L. Thirteen patients (group 3, borderline
      cases) showed either signs of perioperative myocardial ischemia by creatine
      kinase isoenzyme MB (CKMB) activity levels (CKMB > 20 U/L on the first
      postoperative day, 3 patients) or by electrocardiography (new ST-T segment
      alterations, 10 patients). TnT concentrations were comparable to group 1 patients
      and indicated uncomplicated bypass surgery in all 3 patients with solely elevated
      CKMB activities. On the other hand, TnT concentrations in 3 patients with
      electrocardiographic signs of perioperative myocardial ischemia were
      significantly higher than in uncomplicated patients (group 1) with peak values
      exceeding 3.5 micrograms/L. Thus, TnT indicated perioperative non-Q-wave
      infarctions not detected by CKMB activity in these 3 patients. These results are
      in accordance with findings in nonsurgical patients. They suggest a higher
      sensitivity and specificity of cardiac TnT compared to CKMB activity in the
      diagnosis of small perioperative myocardial infarctions after bypass surgery.

PMID- 8305657
TI  - Comparison of cardioprotection with crystalloid and blood cardioplegia in CABG
      patients.
AB  - One hundred patients scheduled for elective coronary artery bypass grafting
      (CABG) were randomly allocated to two groups for myocardial preservation:blood
      cardioplegia (BCP) or crystalloid cardioplegia (CCP). The study protocol
      comprised recording of the following parameters: mode of resumption of cardiac
      rhythm, CK-MB analysis, ECG recording, cardiac output measurement, cross-clamping
      and perfusion times, and clinical outcome. The study period covered the time from
      commencement of anesthesia to the first postoperative morning. Spontaneous
      resumption of sinus rhythm was recorded only in the BCP group (22/51 v 0/49, P <
      0.001). CK-MB values were similar in both groups, but 1 hour postoperatively the
      BCP group had lower values (58.8 +/- 26.7 v 74.5 +/- 31.5 U/L, P = 0.0098 by t
      test). Fifteen patients in the BCP group did not receive any electric
      countershock; this subgroup had very low CK-MB values. There were four
      intraoperative myocardial infarctions in the BCP group and two in the CCP group
      (BCP: 3/51 v CCP: 3/49, P = 0.68). The results suggest better cardioprotection
      with blood cardioplegia in this subgroup of patients. Spontaneous resumption of
      normal cardiac rhythm seems to indicate good myocardial preservation, as
      reflected in markedly lower CK-MB values in this subgroup.

PMID- 8305658
TI  - Improved cardiac performance and reduced pulmonary vascular constriction by
      epinephrine administration via a left atrial catheter in cardiac surgical
      patients.
AB  - Diminished left ventricular contractility and increased right ventricular
      afterload are issues in cardiac surgery. The usual administration of
      catecholamines (epinephrine) via the central venous (CV) catheter increases
      cardiac output, but also may increase pulmonary vascular constriction.
      Epinephrine was, therefore, administered via the left atrial (LA) catheter or the
      CV catheter in 8 cardiac surgery patients, each serving as his or her own
      control. The LA administration of epinephrine has an advantage with its immediate
      effect on the coronary circulation, while avoiding associated pulmonary
      vasoconstriction by passing through the systemic capillary bed before reaching
      the lung. It was found in this study that administration of epinephrine via an LA
      catheter increased the average cardiac output by 1.05 L/min, which was
      significantly (P < 0.05) greater than with administration via the CV catheter.
      With LA administration of epinephrine, systemic arterial pressure (systolic
      arterial pressure and diastolic arterial pressure) (SAP, DAP) were also elevated
      to a greater extent than by CV administration. On the other hand, pulmonary
      arterial pressures (systolic pulmonary arterial pressure and diastolic pulmonary
      arterial pressure) (SPAP, DPAP) were less elevated than by administration via the
      CV catheter. This produced increased coronary perfusion and a smaller increase in
      pulmonary vascular tone by LA administration in contrast to CV administration of
      epinephrine. It is concluded that epinephrine administration via an LA catheter
      improved myocardial performance and pulmonary perfusion due to direct entry of
      the agent into the coronary circulation and partial metabolism while passing
      through the systemic capillary bed before reaching the lung.

PMID- 8305659
TI  - Quantitation of volatile anesthetic-induced depression of myocardial
      contractility using a single beat index derived from maximal ventricular power.
AB  - Development of an index of myocardial contractility that is load independent and
      that can be derived from a single cardiac cycle in vivo has important
      intraoperative ramifications. Recently, a new index of contractile state based on
      maximal ventricular power (the rate of ventricular work) has been proposed that
      appears to fulfill these requirements. This investigation compared the efficacy
      and sensitivity of this novel method of measurement of myocardial contractility
      to the slope (Mw) of the preload recruitable stroke work (PRSW) relationship, an
      established measure of left ventricular function derived from left ventricular
      pressure-segment length loops in dogs before and during volatile anesthetic
      induced cardiac depression. Sixteen experiments in two groups were performed
      using eight dogs chronically instrumented for measurement of aortic and left
      ventricular pressure, left ventricular dP/dt, subendocardial segment length,
      intrathoracic pressure, and thoracic aortic blood flow. The maximal ventricular
      power index (PWRmax/EDL2) was calculated as the product of peak aortic blood
      pressure and peak aortic blood flow divided by the square of end-diastolic
      segment length. Mw was obtained from a series of left ventricular pressure
      segment length loops generated by abrupt vena caval occlusion. Systemic
      hemodynamics and myocardial contractility using these two methods were recorded
      in the conscious state and after 30 minutes of equilibration at 1.25, 1.5, or
      1.75 MAC isoflurane or halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305660
TI  - Pacing-induced left ventricular asynchronies in dogs with critical coronary
      stenosis: mechanisms and effect of anesthetics.
AB  - The mechanisms leading to left ventricular (LV) asynchronies are incompletely
      understood, and reports on the functional significance of asynchronies for the
      affected segments are conflicting. To characterize LV asynchronies, 16
      anesthetized dogs with critical stenosis of the left anterior descending coronary
      artery (LAD) were instrumented to measure subendocardial contractile function
      (sonomicrometry) and the ECG in the LAD territory. The subendocardial ECG was
      also recorded from the anterior basal LV territory. Time of regional S wave
      arrival (TS) and time of onset of segment shortening were determined. The animals
      underwent atrial pacing with increasing frequencies until systolic LAD territory
      contractile dysfunction and eventual LV asynchronies were observed. Six animals
      without LAD stenosis served as controls to define the normal response (mean +/-
      2.SD) to increasing pacing rates of systolic shortening and onset time of segment
      shortening (time difference between TS and onset of segment shortening). LAD
      contractile dysfunction was considered as a systolic shortening below the normal
      range, and LV asynchronies as an onset time of segment shortening above the
      normal range. When LV asynchronies occurred, onset time of segment shortening in
      the LAD territory was 80.1 +/- 4.9 ms versus 14.8 +/- 3.7 ms at control (P <
      0.01); the time difference between S wave arrival in the LAD and circumflex
      territories, however, was unchanged. LV asynchronies were associated with marked
      LAD territory contractile dysfunction (systolic shortening of 9.6 +/- 0.8% v 21.0
      +/- 1.9% at control, after systolic shortening of 31.3 +/- 3.8% v 9.0 +/- 2.6% at
      control; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305661
TI  - Diltiazem and regional left ventricular function during graded coronary
      constriction and propofol anesthesia in the dog.
AB  - Although calcium channel blockers may preserve function in ischemic myocardium,
      they may also produce myocardial depression and dysfunction in the presence of
      decreased coronary flow. This study was designed to examine the issue of possible
      protection afforded by diltiazem against ischemia-induced myocardial dysfunction
      during propofol anesthesia. In eight anesthetized and ventilated dogs, regional
      myocardial (ultrasonic crystals in both left anterior descending [LAD] and left
      circumflex [LC] perfusion areas) and global ventricular function were evaluated
      during progressively severe degrees of myocardial ischemia (LAD constriction)
      before and after intravenous diltiazem (150 micrograms/kg). As coronary flow
      decreased, heart rate increased, and arterial and coronary perfusion pressures,
      left ventricular dP/dt, and cardiac output decreased. Systemic vascular
      resistance was unaffected. Diltiazem without coronary constriction increased
      heart rate, and decreased diastolic arterial pressures, left ventricular (LV) end
      diastolic, coronary perfusion pressures, LV dP/dt max, LAD coronary blood flow,
      stroke volume, and cardiac output. At all levels of coronary constriction
      following diltiazem, there were decreases in systolic and diastolic arterial
      pressures, stroke volume, cardiac output, LV dP/dt, and coronary perfusion
      pressure. Heart rate increased at critical coronary constriction, and then
      remained constant relative to the prediltiazem state. The regional muscle effects
      of the reductions in coronary flow in the LAD perfusion territory included
      decreased systolic shortening and increased postsystolic shortening before and
      after diltiazem. Diltiazem did not alter the magnitude of the alterations in
      systolic or postsystolic shortening brought about by coronary constriction. No
      changes occurred in the LC area.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305662
TI  - Effects of a continuous diltiazem infusion on renal function during cardiac
      surgery.
AB  - Thirty-five male patients undergoing coronary artery surgery were studied to
      investigate renal function during a continuous infusion of the calcium channel
      blocker diltiazem. All patients had preoperative renal function within normal
      limits (serum creatinine below 0.133 mmol/L) and were randomly divided into three
      groups: Control (C), Diltiazem 1 (D1), and Diltiazem 2 (D2). Diltiazem was
      infused in D1 (1 microgram/kg/min) and D2 (2 micrograms/kg/min) patients
      throughout surgery and during the following 36 hours. Glomerular function was
      investigated using the endogenous creatinine clearance while tubular function was
      assessed by means of water and sodium reabsorption tests, as well as urinary
      enzyme activity measurements. Hemodynamic monitoring was performed using a
      pulmonary artery catheter. The glomerular filtration rate of C and D1 patients
      showed a significant fall during cardiopulmonary bypass (CPB) with respect to the
      prebypass period and returned to the baseline values only in the postoperative
      period. A similar change was not observed in D2 patients. The analysis of
      variance demonstrated that the glomerular filtration rate was significantly
      higher in Group D2 versus Group C during and after CPB (P = 0.03 and P = 0.04,
      respectively). Furthermore, after CPB, urinary output was significantly improved
      in D2 patients, both versus C and D1 patients (P = 0.003), notwithstanding a
      lower mean arterial pressure in the D2 Group (P = 0.04 v C Group). Tubular
      function was not influenced by diltiazem infusion. It is concluded that a
      continuous diltiazem infusion, at a dose of 2 micrograms/kg/min during cardiac
      surgery, may be useful to prevent a decrease in glomerular function secondary to
      cardiopulmonary bypass.

PMID- 8305663
TI  - Effects of calcium chloride on verapamil- and diltiazem-pretreated isolated rat
      hearts.
AB  - The effects of calcium chloride on cardiac responses to verapamil and diltiazem
      were investigated using isolated and perfused rat hearts with a Langendorff
      technique. Ionized calcium concentrations were increased approximately from 0.5
      mM to 2.2 mM when the hearts were pretreated with 0.2 mg/L of verapamil or 0.28
      mg/L of diltiazem, or were untreated with calcium blockers. Calcium significantly
      counteracted the negative inotropic effect produced by diltiazem and verapamil.
      In contrast, the negative chronotropic effects of both diltiazem and verapamil
      were potentiated by increasing concentrations of ionized calcium, and this
      potentiation was not eliminated by 1.0 mg/L of atropine. An atrioventricular
      block was induced by both verapamil and diltiazem when ionized calcium
      concentrations were lower than normal. It is suggested from this study that,
      although calcium chloride counteracts the negative inotropic effects of verapamil
      and diltiazem, abruptly increased ionized calcium may cause severe bradycardia
      clinically.

PMID- 8305664
TI  - Profound anemia following cardiac surgery.

PMID- 8305665
TI  - Anesthetic management of a patient with a single ventricle and modified Fontan
      procedure.

PMID- 8305666
TI  - Angiotensin-converting enzyme inhibitors in cardiovascular anesthesia.
AB  - Besides the long-term regulation of extracellular fluid volume, the RAS plays an
      important physiologic role in maintaining venous return and blood pressure during
      acute hemodynamic stresses. ACE inhibitors may therefore alter venous return and
      cardiac output regulation during anesthesia and surgery. This may be regarded as
      a drawback of ACE inhibition when other factors interfere with cardiovascular
      homeostasis; deleterious hemodynamic events may therefore occur when blood volume
      is decreased, which may be frequent during cardiovascular anesthesia and surgery.
      However, the alternative solution should not be to stop ACE inhibitors
      preoperatively. This would allow recovery of RAS control of blood pressure, but
      at the expense of some regional circulations. From this point of view,
      preliminary results from early studies during cardiovascular anesthesia and
      surgery showing redistribution of regional blood flow with inhibition of ACE are
      encouraging; whether postoperative outcome can be improved deserves further
      studies. At this time, the evidence is that ACE inhibition does not allow the
      anesthesiologist to be tolerant of hypovolemia.

PMID- 8305667
TI  - Case 6--1993. Cardiopulmonary bypass in two patients with previously undetected
      cold agglutinins.

PMID- 8305668
TI  - Pro: a pulmonary artery catheter should be used in all patients undergoing
      abdominal aortic surgery.

PMID- 8305669
TI  - Con: pulmonary artery catheters are not routinely indicated in patients
      undergoing elective abdominal aortic reconstruction.

PMID- 8305670
TI  - ST segment depression following intubation.

PMID- 8305671
TI  - Complications with acute plasmapheresis.

PMID- 8305672
TI  - Hypoxemia from transient right-to-left shunting during atrial septal defect
      repair detected by intraoperative transesophageal echocardiography.

PMID- 8305673
TI  - Epinephrine for reversal of atrioventricular block following aortic cross
      clamping and potassium cardioplegia.

PMID- 8305674
TI  - Post-cardiopulmonary bypass neurologic complication: role of funduscopy in early
      diagnosis.

PMID- 8305675
TI  - Introduction: protein tyrosine phosphatases.

PMID- 8305676
TI  - Structural diversity of eukaryotic protein tyrosine phosphatases: functional and
      evolutionary implications.
AB  - In the past few years, very rapid advances have been made in determining the
      primary structure of protein tyrosine phosphatases (PTPases). PTPase genes have
      now been isolated from bacteria, viruses, yeasts and insects as well as
      vertebrates. The cytosolic PTPases have a catalytic domain associated with
      various accessory domains that are believed to be involved in protein-protein
      interaction or subcellular localization. The transmembrane PTPases have either
      one or two cytoplasmic PTPase domains and an extracellular receptor-like
      structure. The existence of a large number of structurally diverse PTPases
      suggests that they play specific and crucial roles in signal transduction. In
      this article, the structural features of the PTPases from higher eukaryotes are
      reviewed.

PMID- 8305677
TI  - Bacterial and viral protein tyrosine phosphatases.
AB  - Unrestricted protein tyrosine phosphatase (PTPase) activity may play a role in
      pathogenesis. For instance, the virulence determinant gene, yopH, of Yersinia
      pseudotuberculosis encodes a PTPase. The phosphatase activity of the YopH protein
      is essential for the pathogenesis of Y. pseudotuberculosis. Yersinia pestis, the
      bacterium which causes the bubonic plague, also contains a gene closely related
      to yopH. The action of YopH on host proteins appears to break down signal
      transduction mechanisms in many cell types including those of the immune system.
      This may contribute to the ability of the bacterium to escape effective
      surveillance by the immune system. The vaccinia virus VH1 gene, like yopH in the
      Yersinia bacteria, encodes a protein phosphatase. The VH1 PTPase defines a new
      class of phosphatases capable of dephosphorylating both phosphoserine/threonine
      and tyrosine containing substrates. Proteins sharing sequence identity to this
      dual-specificity phosphatase have been identified from other viruses, yeast and
      man. Although a complete understanding of the function of these dual-specificity
      phosphatases is not presently available, they clearly play important roles in
      cell cycle regulation, growth control and mitogenic signaling mechanisms. The
      unique catalytic properties of the dual specificity phosphatases suggest that
      these catalysts constitute a distinct subfamily of phosphatases.

PMID- 8305678
TI  - Drosophila protein tyrosine phosphatases.
AB  - Seven protein tyrosine phosphatase (PTPase) genes have been identified in the
      fruit-fly Drosophila melanogaster. Four of these genes encode receptor-linked
      PTPases (R-PTPs) that are expressed on central nervous system axons in the
      embryo. Each axonal R-PTP has an extracellular domain that is homologous to
      vertebrate adhesion molecules and to identified mammalian R-PTPs. Two non
      receptor PTPase genes have been isolated to date. One of these, corkscrew (csw),
      encodes an SH2 domain-containing PTPase that appears to be a homolog of mammalian
      PTP1D. Genetic evidence indicates that the csw PTPase is involved in the
      transduction of signals from receptor tyrosine kinases to their down-stream
      targets, which include Ras proteins.

PMID- 8305679
TI  - The receptor-like protein tyrosine phosphatase alpha: a role in cell
      proliferation and oncogenesis.
AB  - The transmembrane nature of the receptor-like protein tyrosine phosphatases
      (PTPases) suggests that they transduce as yet unidentified extracellular signals
      to intracellular events via a phosphotyrosyl-protein dephosphorylation step,
      although little is known of their regulation and cellular activities.
      Structure/function studies of PTP alpha demonstrate that both catalytic domains
      are required for full enzymatic efficiency and that interdomain interactions may
      modulate PTP alpha activity and specificity. Overexpression of PTP alpha results
      in cell transformation and tumorigenesis, likely as a consequence of the ability
      of PTP alpha to dephosphorylate and activate the c-src tyrosine kinase. This
      suggests a role for PTP alpha in normal cell proliferation. PTP alpha is so far
      unique among the PTPases in terms of its oncogenic potential, and overexpression
      or deregulation of PTP alpha may be involved in the genesis, progression or
      maintenance of certain tumor states.

PMID- 8305680
TI  - The leukocyte common antigen, CD45 and other protein tyrosine phosphatases in
      hematopoietic cells.
AB  - Numerous protein tyrosine phosphatases have been characterized that are expressed
      by hematopoietic-derived cells. CD45, a transmembrane protein tyrosine
      phosphatase expressed by all nucleated cells of hematopoietic origin, has been a
      prototype for studying the function of these enzymes. In T lymphocytes, CD45
      serves to dephosphorylate and activate members of the Src-tyrosine kinase family.
      Without CD45 function, T cells cannot respond to antigen. Therefore, CD45
      functions positively to regulate lymphocyte activation. The characteristics of
      other protein tyrosine phosphatases found in hematopoietic-derived cells suggests
      that they are also essential in regulating cell differentiation and activation.

PMID- 8305681
TI  - Structure and function of SH2-domain containing tyrosine phosphatases.
AB  - The importance of tyrosyl phosphorylation in regulating growth factor-receptor
      mediated signal transduction is firmly established, but the roles of protein
      tyrosine phosphatases (PTPases) in these pathways are unclear. PTPases that
      contain src-homology 2 (SH2) domains, which mediate interactions with specific
      phosphotyrosyl proteins, probably play an important role in early signaling
      events following growth factor stimulation. In this review, the two mammalian SH2
      containing PTPases, SH-PTP1 and SH-PTP2, are described and their possible roles
      in signal transduction discussed. In addition, the implications of recent genetic
      studies in the mouse and Drosophila, which shed light on the actions of these
      PTPases in physiology and pathology, will be addressed.

PMID- 8305682
TI  - Reversible tyrosine phosphorylation and cell cycle control.
AB  - In eukaryotic organisms, reversible tyrosine phosphorylation has been established
      as an important element in the regulation of cell growth and more recently as an
      essential element in the regulation of the cell division cycle. The activity of
      p34cdc2, a protein kinase whose activity is required for the entry of cells into
      mitosis, is tightly controlled by reversible phosphorylation at tyrosine 15. A
      complex network of interacting protein kinases and protein phosphatases regulate
      the state of p34cdc2 tyrosine phosphorylation and therefore the entry of cells
      into mitosis. In the fission yeast Schizosaccharomyces pombe, genes encoding
      several of these protein kinases and protein phosphatases have been obtained
      through genetic approaches. In this review, we will focus on the protein kinases
      encoded by wee1+, mik1+ and cdr1+/nim1+ and the protein phosphatases encoded by
      cdc25+ and pyp1+, pyp2+ and pyp3+. Homologs of many of these regulators have been
      identified and characterized in higher eukaryotes underscoring the importance of
      reversible tyrosine phosphorylation as a universal mechanism for the regulation
      of the cell division cycle.

PMID- 8305683
TI  - Protein tyrosine phosphatases in cell transformation.
AB  - The role of tyrosine phosphorylation in cell transformation has been well
      established. It has been proposed that protein tyrosine phosphatases (PTPases)
      may be capable of dephosphorylating critical substrates involved in the
      transformation process, suggesting that they represent a tumor suppressor family
      of enzymes. Indeed, recent work showed that overexpression of some PTPases in
      malignant cells counteracted the action of oncogenic tyrosine kinases although
      overexpression of other forms of these enzymes increased tumorigenicity. The work
      described herein has provided some insight into the action, both antagonistic and
      synergistic, of the kinases and phosphatases on cell growth and transformation.

PMID- 8305684
TI  - [Computed tomography of the lung: a replacement for the thoracic plain view?].

PMID- 8305685
TI  - [[111In]-DTPA-D-phenylalanine octreotide SPECT for the scintigraphic imaging of
      enhanced somatostatin-receptor density in endocrine ophthalmopathy].
AB  - Recently, [111In]-DTPA-D-phenylalanine-octreotide was introduced for clinical
      use. This radioligand binds specifically to somatostatin receptors and is
      suitable for SPECT examinations. The aim of this study was to clarify whether an
      increased somatostatin receptor density can be imaged and quantified in patients
      with endocrine ophthalmopathy (e.o.). 7 patients between 34 and 55 years with
      e.o. at stages III to VI and 4 controls between 38 and 63 years were examined.
      All patients and controls received approximately 200 MBq [111In]-DTPA-D
      phenylalanine-octreotide by IV injection. A SPECT examination was performed 4
      hours after injection and a normalised tracer uptake (A(n)) was calculated for
      both orbitae. In patients with e.o. the values of A(n) were significantly higher
      compared with controls (P = 0.002). There was a correlation between A(n) and
      exophthalmus stages according to Hertel with r = 0.844 (P = 0.001). These results
      indicate that [111In]-DTPA-D-phenylalanine-octreotide SPECT might be useful for
      the in vivo assessment of an increased somatostatin receptor density in e.o.
      These findings could have an impact on the treatment with somatostatin analogous
      in e.o.

PMID- 8305686
TI  - [Surgically treated thoracic aortic dissection. The angiographic follow-up of the
      perfusion relations].
AB  - Control angiography in arterial DSA technique was performed in 27 patients after
      operative treatment of acute aortic dissection (17 patients with type A
      dissection) respectively chronic aortic dissection (9 patients with type A
      dissection/1 patient with type B dissection). The mean interval between surgery
      and angiography was 59 months. All patients were free from symptoms due to organ
      complications or redissection. Persistent patency of a false lumen was observed
      in 40.7% (52.9% after operative treatment of an acute dissection; 20% after
      operative treatment of a chronic dissection). In all cases with a persistent
      false lumen the dissection originated at the distal anastomosis. In all patients
      the beginning of the dissection and the perfusion of the supra-aortal, visceral
      and iliac vessels whether by the true or false lumen could be shown. In 54.5% the
      Tr. brachiocephalic trunk was involved in the dissection. In 45.5% the left renal
      artery was solely perfused by the false lumen. Angiography in arterial DSA
      technique is evidently a valuable technique to document the beginning and
      extension of a dissection, sufficiency of the aortic valve, re-entries of the
      dissection, perfusion of the aortal branches, and the flow in both channels.

PMID- 8305687
TI  - [The value of spiral computed tomography in the imaging of aortocoronary bypass
      vessels].
AB  - Spiral computer tomography (Sp-CT) was performed on 25 patients with 81 aorto
      coronary bypasses, with persistent symptoms, following selective coronary
      angiography. The purpose was to determine to what extent Sp-CT is able to
      demonstrate patency or occlusion of individual bypasses. From the raw data,
      transverse sections and standardised 3D reconstructions were obtained.
      Statistical evaluation showed a sensitivity of 93% and a specificity of 100% with
      regard to patency. Sp-CT provides optimal contrast and complete demonstration of
      the bypass without movement artifacts from respiration. 3D reconstructions aid in
      the evaluation of complex anatomical situations but occasionally lead to
      incorrect diagnosis of stenoses or occlusions. Compared with other non-invasive
      procedures (conventional CT and NMR) Sp-CT has proved significantly better for
      the evaluation of bypass occlusions. Sp-CT cannot completely replace angiography
      but in some cases may be an acceptable alternative.

PMID- 8305688
TI  - [The color-coded duplex sonography and contrast-enhanced magnetic resonance
      tomography of scintigraphically cold thyroid nodules].
AB  - In order to establish diagnostic criteria, colour-coded duplex sonography was
      performed on 40 patients who had a total of 43 operatively confirmed thyroid
      lesions which were scintigraphically "cold" (28 adenomas, 8 carcinomas, 4 cases
      of thyroiditis and 3 cysts). 32 of these patients also had MRT with T2- and T1
      weighted images before and after injection of Gd-DTPA (0.1 mmol/kg). Adenomatous
      nodules and adenomas showed a peripheral vascular halo on colour-coded duplex
      sonography with a sensitivity of 96% and a specificity of 93%. Malignant lesions
      showed marked central vascularisation and on B-images irregular marginal
      structures. Adenomas and adenomatous nodules showed hyperintense areas on T1
      weighted unenhanced MR images and/or homogeneous uptake in the lesion
      (sensitivity 100%, specificity 77%). Malignant lesions typically showed an
      irregular margin with increased contrast uptake on MRT. If sonography and colour
      coded duplex sonography is unable to classify a lesion with any degree of
      assurance then MRT with Gd-DTPA enhancement should be performed.

PMID- 8305689
TI  - [Breast ductal carcinoma in situ. The clinical image in the mammogram].
AB  - Thirty-one consecutive cases of ductal carcinoma in situ (DCIS) were
      retrospectively analysed to determine the spectrum of mammographic appearances.
      68 per cent of the lesions appeared as microcalcifications, 52% as structural or
      irregular, poorly defined soft-tissue abnormalities, respectively. A mass lesion
      was noted in 23% of cases. 4 patients presenting with DCIS had negative
      mammograms and were diagnosed by means of additional examination techniques such
      as galactography, sonography, and cytologic evaluation in case of bloody nipple
      discharge. The authors conclude that there is a wide spectrum of mammographic
      imaging of DCIS.

PMID- 8305690
TI  - [The initial experiences with a new method for treating invagination: sonography
      guided hydrostatic reduction].
AB  - During the last four months we have been treating all 15 sonographically
      diagnosed intussusceptions by a new method; this is based on the introduction of
      a saline enema under sonographic control. In 13 cases the method was successful
      according to imaging and clinical criteria. In two patients conservative
      reduction was impossible: in one patient partial resection of the ileum was
      necessary and in the other there was a recurrence which was reduced at operation.
      There were no complications. The advantages of the method are reduced radiation
      exposure, complete evaluation of the course of the procedure with definite
      criteria for success, the ability to recognise an ileo-ileal invagination and to
      determine the head of the intussusceptum. We can see no disadvantages compared
      with conventional methods. We regard this method as optimal in future for the
      treatment of infantile intussusceptions.

PMID- 8305691
TI  - [MRT of the liver in Wilson's disease].
AB  - To show that Wilson's disease is one likely cause of multiple low-intensity
      nodules of the liver we obtained MR images in 16 patients with clinically and
      histopathologically confirmed Wilson's disease. Corresponding to morphological
      changes MRI enabled the subdivision of the patients into two groups. Using a T2
      weighted spin-echo sequence (TR/TE = 2000/45-90) liver parenchyma showed multiple
      tiny low-intensity-nodules surrounded by high-intensity septa in 10 out of 16
      patients. 5 patients had also low-intensity nodules in T1-weighted images (TR/TE
      = 600/20). In patients of this group histopathology revealed liver cirrhosis (n =
      7) and fibrosis (n = 2). Common feature of this patient group was marked
      inflammatory cell infiltration into fibrous septa, increase of copper
      concentration in liver parenchyma and distinct pathological changes of laboratory
      data. In the remaining 6 patients no pathological change of liver morphology was
      demonstrated by MRI corresponding to slight histopathological changes of
      parenchyma and normal laboratory data. As low-intensity nodules surrounded by
      high intensity septa can be demonstrated in patients with marked inflammatory
      infiltration of liver parenchyma MRI may help to define Wilson patients with
      poorer prognosis. In patients with low-intensity nodules of the liver and unknown
      cause of liver cirrhosis laboratory data and histopathology should be checked
      when searching for disorders of copper metabolism.

PMID- 8305692
TI  - [The MR tomography of focal liver lesions with the superparamagnetic contrast
      agent AMI-25 at 1.5 tesla].
AB  - Superparamagnetic iron oxide particles (AMI-25) were evaluated as a liver
      contrast agent in high-field MR imaging (1.5 T). 16 patients with up to 5
      presumed focal liver lesions (liver metastases n = 8, HCC n = 5, Klatskin tumours
      n = 2, FNH n = 1) received 15 mumol Fe/kg BW intravenously and were examined via
      standard T1- and T2-weighted spin-echo sequences. Quantitative image analysis
      showed a post-contrast increase of the contrast-to-noise ratio (C/N) from 1.6 to
      7.4 on SE 2,500/15 images (p < .05). However, C/N was in the same range on plain
      SE 2,500/90 scans. Blind evaluation by two independent readers revealed that AMI
      25-enhanced images did not provide a significantly increased number of lesions.
      Two patients reported minor, self-limited side-effects (flush, back pain). We
      conclude that in contrast to reports at mid-field MR imagers, the use of AMI-25
      at 1.5 T does not significantly improve the detection of focal liver lesions on
      conventional SE images.

PMID- 8305693
TI  - [Superparamagnetic iron particles. The clinical results in the MR diagnosis of
      liver metastases].
AB  - The diagnostic value of superparamagnetic iron particles as a tissue-specific MR
      contrast medium of the reticulo-endothelial system was studied in 30 patients.
      All patients had liver metastases (maximally 5 known metastases on MR). The
      patients were examined on a 1.5 Tesla scanner before and after a slow intravenous
      injection of iron particles (AMI-25) at a dose of 15 mumol/kg. Contrast injection
      led to a significant reduction of signal strength in the liver parenchyma (p < or
      = 0.001) but not in the metastases. Contrast enhanced spin echo sequences (SE
      2300/45) provided the most marked liver/tumour contrast, greater than the
      contrast values of T1- and T2-weighted images (p < or = 0.01). After the
      intravenous injection of iron particles, small metastases in particular are more
      easily demonstrated. A new, rapid T2-weighted pulse sequence (PSIF 10/15/15
      degrees) results in the elimination of vascular signals and leads to better
      differentiation between lesions and intrahepatic vessels. The use of
      superparamagnetic iron particles as an MR contrast medium improves the
      demonstration of liver metastases.

PMID- 8305694
TI  - [The use of new turbo spin-echo pulse sequences with and without fat suppression
      in the diagnosis and staging of prostatic carcinoma].
AB  - MR studies using turbo spin-echo pulse sequences (TSE) were performed on 27
      patients with histologically confirmed prostate cancer. A prospective study was
      conducted in 15 patients who underwent radical prostatectomy. Turbo SE pulse
      sequences generate strongly T2-weighted images of excellent quality with
      reduction of measurement time by a factor of 4-6. A comparison with standard T2
      weighted spin-echo pulse sequences indicated an objective improvement in the
      contrast of pathological structures (p < 0.001). With respect to differentiation
      of stages T2 and T3 (TNM) during pathohistological correlation, sensitivity of
      80%, specificity of 40% and an accuracy rate of 67% were obtained. Sensitivity of
      71% and specificity of 75% were obtained when decoding cases of infiltration into
      the seminal vesicles, with an accuracy rate of 73%.

PMID- 8305695
TI  - [The technic and value of the 3-dimensional imaging of renal calyx staghorn
      calculi with spiral CT].
AB  - 5 patients with staghorn calculi in the renal pelvis were examined by spiral CT.
      From the raw data three dimensional reconstructions of the stones were obtained.
      In all patients it was possible to compare the three dimensional model with the
      stone following performance of percutaneous litholapaxy and endoscopic removal of
      the fragments. In all cases the three dimensional reconstruction provided a
      realistic image of the stones and was of practical value for the urologist for
      preoperative diagnosis and intraoperative control.

PMID- 8305696
TI  - [Ultrasound-guided fine-needle biopsy with an automatic full-incision system: the
      initial experiences and comparison with a conventional biopsy gun].
AB  - The purpose of this study was to evaluate the efficacy of a new automatic biopsy
      device (Autovac, Angiomed, Karlsruhe, Germany) in ultrasound (US) guided biopsies
      of focal abdominal lesions. 50 consecutive patients with focal abdominal lesions
      underwent US guided biopsies. In the first 24 patients, needle passes were
      performed with the Autovac system (outer diameter 0.95 mm) as well as with the
      Biopty gun (outer diameter 0.9 mm) (Bard Covington, USA). The size and the
      quality of the histologic and the cytologic material obtained by both systems
      were evaluated by histopathologists blinded to the system used. Autovac yielded
      significantly more material (defined as the area of the obtained tissue cores)
      and a significantly higher quality score than did the Biopty system. 96% of the
      histologic specimen and 100% of the cytologic smears obtained with Autovac were
      diagnostic, compared to 70 and 81% with Biopty, respectively. With the exception
      of a short-time elevation of the blood pressure in one patient, no complications
      occurred. The results indicate an advantage of the automatic full-cut type system
      Autovac over the tru-cut type Biopty gun in US-guided biopsies of focal abdominal
      lesions.

PMID- 8305697
TI  - Sonographically guided needle biopsy in peripheral thoracic masses: results in 50
      patients.
AB  - 50 patients with thoracic lesions were selected for percutaneous biopsy guided by
      real-time sonography. The indications were pulmonary, pleural and mediastinal
      lesions which made contact with the chest wall and sonographically accessible.
      Included were lesions near vital structures in the mediastinum (n = 3), in the
      apex of the lung (n = 8), small pulmonary nodules in contact with the chest wall
      (n = 24), lesions with intervening pleural fluid (n = 2), pleural nodules (n = 9)
      and masses arising from the chest wall itself (n = 4). A definitive diagnosis was
      established in 38 of the 45 (84.4%) malignant lesions and in 4 of the 5 (80%)
      benign lesions. Complications were restricted to one pneumothorax.
      Sonographically guided biopsy can be carried out as a bedside procedure. Real
      time monitoring compensates for respiratory movements. Its role is curbed by
      intervening air such as in aerated lung, pneumothorax or primarily cavitatory
      lesions.

PMID- 8305698
TI  - [CT-guided biopsies of the axial skeleton. The approaches and results].
AB  - The value of percutaneous CT-guided biopsies of the axial skeleton for
      establishing a diagnosis is determined from a series of 75 punctures in 74
      patients in retrospect. Indications showed benign conditions to prevail over
      malignant lesions by a ratio of 1.6:1. Biopsy routes turned out to be strongly
      determined by regional anatomy allowing for a standardised procedure in each
      area. 64 out of 75 histological diagnoses were confirmed by open surgery (n = 17)
      or follow-up (n = 58) accounting for an accuracy of 85.3%. In 7 cases no definite
      diagnosis could be made from the sample and in 4 cases the diagnosis proved false
      although tissue cores could be obtained in each case. No serious or irreversible
      complications occurred. CT-guided punctures of the axial skeleton are considered
      a safe and highly accurate procedure to establish a definite diagnosis unless
      there is a primary indication for surgery or the need for decompression.

PMID- 8305700
TI  - [Complete sinistroposition of the vena cava inferior].

PMID- 8305699
TI  - [Laser thermal venous obliteration: experimental results in the rat model].
AB  - In an animal study, thermal laser application was tested for inducing venous
      thrombosis. In 54 rats, metal-tipped laser catheters ("hot tip") were trans
      jugularly inserted into the distal inferior caval vein which was thermally
      damaged by laser pulses of 4-7 W. Suitable energy levels were defined in an acute
      experiment in 25 rats. Chronic experiment with 29 rats included survival time of
      two weeks after laser application, autopsy and histological work-up of the caval
      vein. In 27 rats, laser application was successfully performed and induced
      thrombosis in 17 animals. Perforation of the caval vein occurred in 10 rats.
      Thermal laser application is capable of inducing venous thrombosis. The power
      ranges inducing thrombosis or thermal perforation are, however, too narrow to
      allow safe clinical application of this technique.

PMID- 8305701
TI  - [Intrathoracic goiter. Computed tomographic aid to a diagnostic decision for a
      surgical procedure].

PMID- 8305702
TI  - [Invasive plasma-cell granuloma of the mediastinum].

PMID- 8305703
TI  - [Pericardial rupture in aortic dissection with hemopericardium].

PMID- 8305704
TI  - [The magnetic resonance tomography of so-called transient osteoporosis].

PMID- 8305705
TI  - Expression of Xenopus snail in mesoderm and prospective neural fold ectoderm.
AB  - Expression of the Xsna gene during Xenopus laevis embryogenesis has been analysed
      by in situ hybridisation. Like its homologue snail in Drosophila, Xsna is
      expressed zygotically in all early mesoderm. Expression starts during stage 9 in
      the dorsal marginal zone and spreads to the ventral side by stage 10. During
      gastrulation, each cell begins to express as it involutes so that cells newly
      expressing Xsna are added to the forming mesoderm mantle in an anterior-to
      posterior progression. Xsna expression is then down-regulated in a tissue
      specific fashion that reveals the subdivision of the mesoderm before its
      derivatives are overtly differentiated; e.g., the appearance of the notochord,
      myotomes, and pronephroi are preceded by the disappearance of Xsna mRNA, while
      undifferentiated mesoderm remains labelled, even into tadpole stages. Xsna is
      expressed in the suprablastoporal endoderm during gastrulation and in its
      derivatives, the prechordal and sub-notochordal endoderm, during neurulation.
      Relationships between Xbra, Xtwi, and Xsna expression are examined. Xsna is also
      expressed in the prospective neural fold ectoderm from stage 11 in a low arc
      above the dorsal marginal zone, precisely identifying a distinct band of cells
      that surrounds the prospective neural plate that we designate the neural plate
      border. The anterior transverse neural fold, which becomes forebrain, ceases Xsna
      expression during neurulation. In the longitudinal neural folds, the deep and
      superficial ectoderm compartments labelled by Xsna expression are the prospective
      neural crest and prospective roof of the neural tube, respectively. Xsna
      expression persists in the neural crest during migration and in some derivatives
      at least until metamorphosis but ceases in the roof of the neural tube soon after
      neurulation.

PMID- 8305706
TI  - Collagen type VI in neural crest development: distribution in situ and
      interaction with cells in vitro.
AB  - We have examined the spatio-temporal distribution of collagen type VI (Col VI)
      during neural crest development in vivo and its ability to promote neural crest
      cell attachment and migration in vitro. An affinity purified antiserum and chain
      specific monoclonal antibodies against chicken Col VI were employed to
      immunolocalize the collagen in tissue sections and by immunoblotting. At stages
      of initial neural crest cell migration, the alpha 1(VI) and alpha 2(VI) chains
      were immunolocalized in apposition with basement membranes of the neural tube,
      somites, notochord and ectoderm, whereas no immunoreactivity was seen for the
      alpha 3(VI) chain. Immunoblotting analysis confirmed the expression of alpha
      1(VI) and alpha 2(VI) chains and the lack of detectable immunoreactivity for the
      alpha 3(VI) chain at these early phases of neural crest development. Conversely,
      at advanced phases of migration and following gangliogenesis, expression of alpha
      3(VI) chain coincided with that of alpha 1(VI) and alpha 2(VI) chains in
      apposition with basement membranes, around the dorsal root ganglia, and in
      fibrillar arrangements within the developing dermis and ventral sclerotome. The
      ability of Col VI to promote neural crest cell attachment and migration was
      tested in vitro using quantitative assays for these processes. Both native
      microfilaments and isolated tetramers of Col VI strongly promoted neural crest
      cell attachment and migration. Optimal stimulation of neural crest cell adhesion
      and migration was dependent upon structural integrity of Col VI since unfolded
      and disassembled alpha chains only weakly promoted cell attachment and were
      virtually inactive in supporting cell movement. The importance of a native
      macromolecular organization of Col VI further was analyzed in experiments in
      which dissociated tetramers were reassociated by Ca(2+)- and temperature
      dependent self-aggregation. In contrast to native microfilaments, these
      oligomeric complexes were less effective in promoting neural crest cell movement,
      but still retained the ability to stimulate maximal cell attachment. The results
      indicate that Col VI is a primary component of the extracellular matrix deposited
      along neural crest migratory pathways, where it may participate in the regulation
      of cell movement by functioning as a migratory substrate. The ability of Col VI
      to promote neural crest cell adhesion and motility is highly dependent upon
      maintainance of a native macromolecular arrangement.

PMID- 8305707
TI  - Developmental patterns of two alpha 1(IX) collagen mRNA isoforms in mouse.
AB  - Northern blot hybridization, reverse-transcription polymerase chain reaction (RT
      PCR), and RNase protection assays were used to examine the expression of two
      alpha 1(IX) collagen mRNA species (long and short form) in developing mouse
      tissues. Furthermore, in situ hybridization was used to identify cells expressing
      the Col9a1 gene during eye development. The results indicate that during
      embryonic development eye and heart preferentially express the short form; lung
      and cartilage express the long form; whereas liver expresses a very low level of
      long form alpha 1(IX) mRNA which can only be detected by RT-PCR. In situ
      hybridization demonstrated that at 10.5 day postcoitum (d.p.c.), the alpha 1(IX)
      collagen mRNAs were first expressed in optic cup (neural ectoderm) but not in
      lens vesicle (surface ectoderm). By 13.5 d.p.c., the cells that express the alpha
      1(IX) mRNA progressively were concentrated toward the anterior part of the neural
      retina. By 16.5-18.5 d.p.c., the hybridization signals were found exclusively in
      the inner non-pigmented layer of the presumptive ciliary epithelium. As ciliary
      epithelial cells become well differentiated 3 weeks after birth, cells expressing
      the Col9a1 gene were limited to the junction between mature ciliary folds and the
      neural retina. No hybridization signal could be detected in ocular tissues of
      mouse older than 6 weeks. It is of interest to note that a hybridization signal
      was not detected in cornea at the various developmental stages examined,
      suggesting that mouse cornea does not significantly express alpha 1(IX) mRNA
      during embryonic development. This differs from that of chick cornea development.
      In summary, the expression of the Col9a1 gene shows a temporospatial pattern
      throughout mouse eye development.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305708
TI  - Test of a model for the effects of retinoic acid on urodele limb regeneration.
AB  - Previous studies have shown that in axolotls (Ambystoma mexicanum), retinoic acid
      (RA) treatment evokes pattern completion in limb regenerates derived from
      anterior and dorsal half zeugopodia (lower arms and legs), but causes
      regenerative failure in posterior and ventral half zeugopodia. Pattern completion
      in anterior and dorsal half limbs may be explained by postulating that
      intercalary regeneration occurs in the antero-posterior (AP) and dorsoventral
      (DV) axes between blastema cells that are posteriorized (anterior half limb) or
      ventralized (dorsal half limb) by RA, and circumferential anterodorsal cells that
      remain unaffected by RA and thus maintain their original positional identities.
      The contrasting regenerative failure of RA-treated posterior and ventral half
      zeugopodia may likewise be explained by postulating that all the blastema cells
      in the posterior half are posteriorized, and all the cells in the ventral half
      are ventralized by RA, thus eliminating differentials in transverse positional
      identity essential for blastema formation and outgrowth. To test these postulates
      we grafted blastemas derived from limbs halved in the AP and DV axes of control
      and RA-treated animals to untreated whole limb stumps and analyzed the patterns
      of supernumerary (SN) regeneration. The site or location of SN formation will
      demonstrate (1) whether RA has posteriorized and ventralized the positional
      identity of the blastema cells and (2) if blastema cells in the periphery of the
      anterodorsal quadrant of the limb are resistant to these RA-induced changes in
      positional identity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305709
TI  - Role of the brachial somites in the development of the appendicular musculature
      in rat embryos.
AB  - DiI, a fluorescent lipophilic dye, was micro-injected into the brachial somites
      of 10.5 day rat embryos to determine whether these somites can contribute cells
      to the development of the fore-limb bud. The injected embryos were cultured and
      harvested at the 20-25-somite stage. The dye did not interfere with somitogenesis
      because, at the injection site, the DiI-labelled somites were able to
      differentiate into dermomyotome and sclerotome. We have analyzed cryo-sections of
      20-21-somite stage embryos and were unable detect the presence of DiI-labelled
      cells in the fore-limb buds. However, at the 22-somite stage, a few DiI-positive
      cells were found in the proximal region of the limb bud. These labelled cells had
      migrated into the limb from the lateral border of the dermomyotome. From the 23
      somite stage onwards, there were even more DiI-positive cells inside the limb. We
      have performed an additional set of experiments to confirm that the somitic cells
      do have the ability to invade and colonize the limb bud. This was achieved by
      first labelling newly formed somites isolated from the caudal region of 10.5 day
      embryos with DiI and then grafting them into corresponding regions in 8-11-somite
      stage hosts. The donor somites were not orientated when they were implanted into
      the host. However, this did not disrupt their ability to undergo normal
      somitogenesis. We have detected the presence of DiI-positive cells in the limb
      buds of approximately 71% of the 19-30-somite stage embryos that have been
      examined. This is similar to what we obtained for the injected embryos.
      Nevertheless, there is one slight difference and that is the stage the somitic
      cells begin their invasion of the limb. For the injected embryos, migration began
      at the 22-somite stage but in the transplanted embryos, it commenced as early as
      the 18-somite stage. We have also investigated the myogenic potential of the fore
      limb bud at various stages of development to ascertain whether there is a
      correlation between the stage the somitic cells first appear in the limb bud and
      the stage the bud acquires the capacity to form skeletal muscles. This was
      realized by culturing fore-limb buds excised from 18-30-somite stage embryos
      conventionally and in the kidney capsules of adult rats. In both methods, bone
      and cartilage were present in all of the cultures whereas skeletal muscles were
      only present in cultured explants older than the 21-22-somite stage.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8305710
TI  - Fibroblast behavior in the embryonic chick heart.
AB  - Intracardiac fibroblasts (mesenchymal cells) of Hamburger and Hamilton stage 36
      chick heart reside in the epicardium and atrioventricular valves. The
      characteristics of the epicardial fibroblasts include segregation from the
      myocytes of the heart wall myocardium, voluminous extracellular matrix
      production, and some cell proliferation activity. The atrioventricular
      fibroblasts intermingle with myocytes at the mutual border between these tissues,
      produce smaller amounts of extracellular matrix, and show very active cell
      proliferation. Is the behavior of each population of fibroblasts predetermined or
      is each responding in a reversible fashion to local environment? A cell aggregate
      culture system, which permits 3-dimensional cell-cell and cell-matrix
      interactions, is used to study the behavior of each isolated population of
      fibroblasts in vitro. In the presence of serum-free medium, each population
      produces very little extracellular matrix, has relatively low mitotic activity,
      and does not segregate from myocytes when the aggregate is composed of randomly
      intermixed myocytes and fibroblasts. In the presence of chicken serum, each
      population increases matrix production, increases cell proliferation, and sorts
      from myocytes. Thus, we suggest that the two populations of fibroblasts in the
      developing heart are responding to local environments and the differences
      observed in vivo are not the consequence of irreversible states of cellular
      differentiation.

PMID- 8305711
TI  - Studies of human airways in vitro: a review of the methodology.
AB  - The pathophysiology of human airway narrowing is only partly understood. In order
      to gain more insight in the mechanisms of human lung diseases and potential
      beneficial therapeutic agents, adequate models are needed. Animal airway models
      are of limited value since lung diseases such as asthma and chronic obstructive
      pulmonary disease (COPD) are unique to humans and because the mechanisms of
      airway narrowing differ between species. Therefore, it is important to perform
      studies on human isolated airways. We describe the models that have been
      developed to study airway function in vitro, emphasizing human airway
      preparations. The easily prepared airway strip and ring preparations are
      described first. The potential damage during preparation and the interference
      with airway structure are important drawbacks in these preparations. Lung
      parenchymal strips, described next, were designed in order to study
      responsiveness of small airways. However, parenchymal strips are anatomically
      complex, and responsiveness is determined by the relative amounts of airway and
      vascular smooth muscle. The lack of reproducibility between species and even
      within one animal limits their usefulness. Airway tube preparations, in which
      luminal and serosal stimulation can be separated, enable us to study the
      modulatory role of the airways epithelium in vitro. Furthermore, airway
      compliance can be measured. In the isolated perfused lung preparation,
      relationships between the airways and the vascular system are preserved and the
      interaction between these two systems can be studied. Weight gain due to fluid
      extravasation is a problem in this model which has not been used yet to study
      human lungs in vitro. Next, methodological aspects such as tissue handling and
      storage, recording of responses, removal of the epithelium, and electrical field
      stimulation are discussed in some detail. Although animal airways tissue can be
      studied immediately after removal, human tissue is often obtained with some
      delay. However, this seems tenable since electron microscopy of lung tissue
      obtained at autopsy showed that recovery of the preparation occurs during
      incubation of carbogenated Krebs-Henseleit (K-H) buffer. Dissected airways can be
      stored overnight in cooled K-H buffer until up to 55 hr after resection without
      losing viability. Commonly used physiological salt solutions which bath the
      tissue contain osmotic molecules, ions important for contractility, glucose as a
      substrate, and a bicarbonate-carbon dioxide buffer.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8305712
TI  - Automated histomorphometry of interstitial reactions in the heart.
AB  - A method is presented suitable to measure changes in area densities of the total
      Sirius red-stained interstitial tissue in longitudinal sections of rat hearts by
      means of computer-aided image analysis considering at the same time the behavior
      of six regions and changes in the percentage of thick connective tissue fibers in
      the total interstitial tissue. Verification tests were directed to the influences
      of preparation, adjustment of the grey-level thresholds, and identification of
      the various regions, to marginal conditions of measurement and the investigators.
      The reliability of the method with acceptable total errors is demonstrated.

PMID- 8305713
TI  - LTB4-induced transient neutropenia in the rat: a model for evaluating efficacy
      and bioavailability of LTB4 receptor antagonists.
AB  - An animal model of leukotriene B4- (LTB4) induced neutropenia has been developed
      to evaluate LTB4 receptor antagonists in vivo. LTB4, a potent chemotactic
      inflammatory mediator, when administered intravenously, induces a profound,
      rapid, and transient redistribution of blood neutrophils from the circulating
      pool to the marginated pool. This phenomenon is applied in the neutropenia model
      whereby circulating blood neutrophil counts prior to and after intravenous
      infusion of LTB4 are compared. Kinetics of LTB4-induced neutrophil responses are
      determined through the use of a Technicon H*1 automated blood cell analyzer. LTB4
      receptor antagonists are identified by inhibition of LTB4-induced neutropenia.
      Standard antiinflammatory compounds including BW-755C, Abbott A-64077 (zileuton),
      dexamethasone-21-acetate, indomethacin, and naproxen did not affect LTB4-induced
      neutropenia. A potent LTB4 receptor antagonist, designated "RPR," inhibited LTB4
      induced neutropenia following oral administration in a dose-dependent fashion.

PMID- 8305714
TI  - Monitoring of Ca(2+)-transients in electrically stimulated A7r5 vascular smooth
      muscle cells fills the experimental gap between KCL-induced depolarization and
      patch-clamp studies.
AB  - The effects of electrical field stimulation on [Ca2+]i in the A7r5 vascular
      smooth muscle cell line have been monitored with the Ca(2+)-sensitive dye fura-2.
      The experimental set-up allowed high-temporal resolution of the [Ca2+]i
      measurements and fast application of test solutions. Electrical field stimulation
      of A7r5 cells in the confluent growth state resulted in a transient increase in
      [Ca2+]i from resting values below 100 nM to values in the range of some hundred
      nM. For a given cell, the electrically induced Ca(2+)-transients were highly
      reproducible. The requirement for the presence of extracellular Ca2+ and the
      sensitivity to the Ca(2+)-antagonist nifedipine and the Ca(2+)-agonist BAY K 8644
      suggest that the Ca(/+)-transients reflect [Ca2+]i-changes based on Ca(2+)-influx
      through voltage-dependent L-type Ca(2+)-channels. Therefore, electrical field
      stimulation of confluent A7r5 cells provides an easy-to-establish and highly
      reproducible method for the investigation of the physiology and pharmacology of
      voltage-dependent Ca(2+)-channels in intact vascular smooth muscle cells, which
      fills the gap between KCl-induced depolarization and the patch-clamp technique.

PMID- 8305715
TI  - Electrical field stimulation causes oxidation of exogenous histamine in Krebs
      Henseleit buffer: a potential source of error in studies of isolated airways.
AB  - Electric field stimulation (EFS) relaxes human histamine-precontracted airways in
      vitro. This relaxation is only partly neurally mediated. Nonneural relaxation has
      been also shown in blood vessels and is due to the generation of oxygen radicals
      by EFS. In isolated airways the origin of the nonneural component of the
      relaxation is not clear. Because exogenous catecholamines are oxidized during EFS
      of carbogenated Krebs-Henseleit (K-H) buffer, we questioned whether this is also
      the case for exogenous histamine. Human airways precontracted with histamine or
      methacholine were exposed to either EFS-stimulated carbogenated K-H buffer that
      also contained histamine or methacholine or unstimulated buffer. Airways exposed
      to EFS-stimulated buffer that contained histamine relaxed, whereas airways
      exposed to buffer containing methacholine or exposed to unstimulated buffer did
      not. It appeared that the histamine concentrations in the organ baths decreased
      during 30 min of EFS. This decrease was significantly reduced in the presence of
      ascorbic acid. We conclude that EFS causes oxidation of histamine in carbogenated
      K-H buffer, and this may at least partly explain the nonneural component of EFS
      induced relaxations of precontracted human isolated airways. Therefore, histamine
      should not be used to induce precontraction in EFS experiments.

PMID- 8305716
TI  - The influence of high glucose levels and/or hyperosmolarity on rat isolated
      aorta.
AB  - We investigated the influence of high-glucose levels (30.5 mmol/L) and/or
      hyperosmolarity on pharmacological responses in aortic ring preparations taken
      from nondiabetic rats. Moderate changes were observed for the concentration
      response curves of noradrenaline and phenylephrine, but not for methoxamine and
      cirazoline. Maximal active forces of the concentration-response curves of
      potassium chloride and calcium chloride were significantly reduced by the
      elevated glucose levels per se, but neither the slopes of the curves nor the 
      logEC50 values were affected. Concentration-response curves of serotonin and U
      46619 were not affected. For angiotensin II, the -logEC50 values and maximal
      active forces of the concentration-response curves were significantly lower under
      both hyperglycemic and hyperosmolar conditions. The present study suggests that
      potential changes in contractile behavior in isolated vessels from diabetic
      animals cannot be attributed to high glucose levels and/or hyperosmolarity as
      such, but indeed reflect vascular changes associated with the diabetic state. An
      exception has to be made for the depolarization of aortic ring preparations of
      nondiabetic rat; the elevated glucose level leads to an impaired calcium influx
      via the (slow) L-type calcium channels.

PMID- 8305717
TI  - Prostacyclin generation by rat aortas obtained by different procedures.

PMID- 8305718
TI  - Erythrocyte adenosine transport. A rapid screening test for cardiovascular drugs.
AB  - An erythrocyte (RBC) model based on whole blood was used to investigate the
      effect of cardiovascular drugs on the uptake of adenosine in vitro. Fresh whole
      blood obtained from healthy volunteers was allowed to equilibrate with various
      concentrations (5-1000 microM) of a tested agent. (2-3H)-Adenosine was used as a
      substrate, and the reaction was terminated after 2 sec of incubation at room
      temperature by rapid addition of a "Stopping Solution" which was a mixture of
      erythro-9-(2-hydroxy-3-nonyl)adenine, dipyridamole, and EDTA. The mixture was
      centrifuged (1760 g, 4 degrees C, 10 min), and the radioactivity of an aliquot of
      the supernatant was determined by a scintillation counter. The results showed
      that dipyridamole was the most potent agent tested (IC50 = 0.2 microM). Amongst
      the calcium antagonists studied, isradipine was most potent, followed by
      verapamil, clentiazem, diltiazem, and then nifedipine. The racemates of two
      metabolites of diltiazem, MX and MB, were more potent than the parent drug. The
      antiarrhythmic agents, amiodarone and sotalol, the two new lipid peroxidation
      inhibitors, U-74389F and U-78517F, and the anxiolytic agent, alprazolam, were as
      active as verapamil. The beta-receptor antagonist propranolol and the angiotensin
      converting enzyme (ACE) inhibitor, enalapril, were practically inactive. In
      addition, the model was stereoselective such that the S(-)-enantiomer of
      verapamil was considerably more potent than the R(+)-antipote, whereas d(+)
      sotalol was practically inactive compared to racemic sotalol.

PMID- 8305719
TI  - Enhancement of aortic cholesterol deposition by dietary linoleic acid in
      cholesterol-fed mice: an animal model for primary screening of
      antiatherosclerotic agents.
AB  - We tried to develop an experimental model using mice for the primary screening of
      antiatherosclerotic agents. Male ICR strain mice were given a high-cholesterol
      diet supplemented with 10% linoleic acid for 14 weeks. Throughout the
      experimental period, weight gain of these mice was significantly inhibited as
      compared to that of control mice given a basal diet, but displayed a steady
      increase comparable to that of the high-cholesterol diet without linoleic acid.
      The cholesterol and linoleic acid-fed mice showed increased serum cholesterol and
      phospholipid levels, and decreased serum triglyceride and high-density
      lipoprotein-(HDL) cholesterol levels and lecithin/cholesterol acyltransferase
      (LCAT) activity, as well as a markedly increased lipid peroxide level which was a
      characteristic appearance in the serum of this mouse model. At the end of the
      experiment, uniform and significant increases in cholesterol, notably cholesteryl
      ester, were observed in the aorta. Also found were marked decreases in the aorta
      contents of desmosine and isodesmosine, which are cross-linking amino acids
      present only in the elastin. Histological observations showed accumulations of
      fatty droplets in the intima. These changes were much less in mice receiving a
      high-cholesterol diet without linoleic acid. In this mouse model, probucol
      prevented elevation of serum cholesterol, phospholipid, and cholesterol
      accumulation in the aorta. Increases in lipid peroxide level and decreases in
      LCAT activity were also prevented. These findings indicate that this mouse model
      is useful for primary screening of antiatherosclerotic agents with antioxidative
      activity.

PMID- 8305720
TI  - Mechanisms of gastrulation and tail formation in ascidians.
AB  - Ascidian embryos are useful for examining how events that occur during
      fertilization and cleavage affect gastrulation because they gastrulate early in
      development, during the seventh cleavage. In ascidians, both dorsal-ventral and
      anterior-posterior axes are determined before first cleavage. The dorsal-ventral
      axis is fixed along the animal-vegetal axis of the fertilized egg following the
      first phase of ooplasmic segregation, perhaps due to determinants moved to the
      vegetal pole in concert with the myoplasm and plasma membrane components. The
      first ooplasmic movements appear to be driven by the actin network in the
      cortical myoplasm. The anterior-posterior axis becomes apparent after the second
      phase of ooplasmic segregation, when the cortical myoplasm becomes detached from
      the egg membrane, and moves to the posterior pole of the embryo. This movement is
      dependent on microtubules and has been attributed to the formation and movement
      of the sperm aster. A major component of the cortical myoplasm, p58, is co
      localized along the microtubules emanating from the sperm aster. Gastrulation
      begins during the seventh cleavage with the invagination of the large endodermal
      cells at the vegetal pole of the embryo. The neural plate appears as a thickening
      of the epidermis on the dorsal side of the larva during the ninth cleavage; then
      the neural folds are formed, join, and close, elaborating the neural tube.
      Following neurulation, the tail is elongated as the neural tube and notochord
      cells intercalate at the midline of the embryo. Investigations using anural
      (tailless) ascidian larvae suggest that some of the processes underlying
      elongation can be restored by the zygotic genome. Although ascidian larvae
      contain fewer cells and cell types than vertebrate embryos, ascidian gastrulation
      and morphogenesis appear to employ similar mechanisms to those in vertebrate
      embryos. The extent of our current knowledge about the mechanisms involved in
      gastrulation and tail formation is summarized, and further experiments are
      suggested to explore the molecular mechanisms underlying these processes.

PMID- 8305721
TI  - Evolutionary modifications of morphogenetic mechanisms and alternate life history
      strategies in ascidians.
AB  - Comparative embryological studies using anural and urodele ascidians provide an
      experimental system to study interactions between developmental and evolutionary
      mechanisms that produce alternate life history strategies. In this paper,
      cellular features of anural morphogenesis in Molgula pacifica are compared to
      morphogenesis in species that develop tailed (urodele) larvae and other anural
      molgulid species. The results of these studies are discussed with regard to
      possible mechanisms responsible for the evolution of anural morphogenesis and the
      ecological consequences of anural development. Early developmental processes
      including ooplasmic segregation, cleavage patterns, and the site and timing of
      gastrulation were similar in M. pacifica compared to urodele embryos and embryos
      produced by other anural species. The limited extent of invagination caused by
      large, yolky cells that restricted vegetal pole cell movements in M. pacifica
      gastrulae contrasted with the extensive movements of vegetal pole cells that
      accompanied invagination in M. provisionalis embryos and the embryos of four
      urodele species. The modified mode of gastrulation exhibited by M. pacifica
      embryos is likely due to the relatively high yolk content of their eggs. The
      developmental fates of muscle and epidermal progenitor cells in M. pacifica
      embryos were altered compared to urodele embryos. Ultrastructural studies and
      acetylcholinesterase histochemistry experiments indicate that muscle progenitor
      cells have lost their potential to develop muscle cell features. This loss in
      myogenic potential suggests that muscle progenitor cells were re-programmed to
      die. However, this possibility was not supported by the results of
      ultrastructural studies. A second possibility is discussed in that muscle
      progenitor cells may have been re-specified to differentiate into adult cells
      after metamorphosis. Evidence is presented suggesting that the timing mechanism
      responsible for controlling the onset of metamorphosis, first evident by the
      outgrowth of epidermal ampullae, was modified in M. pacifica. This paper
      concludes with a discussion of how anural morphogenesis altered the ancestoral
      urodele life cycle and the possible ecological benefits of these evolutionary
      alterations.

PMID- 8305722
TI  - Gastrulation in the mouse embryo: ultrastructural and molecular aspects of germ
      layer morphogenesis.
AB  - Ultrastructural studies and lineage analyses of gastrulating mouse embryos have
      revealed that different morphogenetic tissue movements are involved in the
      formation of the three definitive germ layers. Definitive ectoderm is formed by
      epibolic expansion of the pre-existing progenitor population in the embryonic
      ectoderm. Formation of the mesoderm and the endoderm is initiated by cellular
      ingression at the primitive streak. The mesodermal layer is established by cell
      migration and cell sheet spreading, but the endoderm is formed by replacing the
      original primitive endodermal population. To this date, genes that are expressed
      during mouse gastrulation mostly encode cell surface adhesion or signalling
      molecules, growth factors and their receptors, and putative transcriptional
      factors. Their precise role during gastrulation remains to be investigated.

PMID- 8305723
TI  - Morphogenesis of the avian trunk neural crest: use of morphological techniques in
      elucidating the process.
AB  - Morphological data generated from light and electron microscopy form the basis of
      our understanding of avian morphogenesis. Because chicken embryos are readily and
      cheaply obtained and are easily accessible for experimental manipulation,
      morphogenetic processes have been studied extensively in this species. Such
      studies have allowed us to identify the cells involved during morphogenesis,
      observe the shape changes or cellular translocations that accompany a
      morphogenetic process, and determine the timing of these events. Elucidation of
      the molecular basis of morphogenesis has awaited the integration of several
      additional approaches. Among these are experimental embryology, which has allowed
      us to understand cellular behavior associated with morphogenesis;
      immunocytochemistry, which has identified the macromolecular cues that regulate
      cell movements and the environmental factors that control them; and molecular
      techniques, which will permit us eventually to clarify the genetic regulation of
      morphogenesis. Although current research in development is heavily biased towards
      molecular biology, morphological studies continue to frame the questions that are
      now being addressed using molecular techniques. This review focuses on the cells
      of the neural crest as a model system where questions of avian morphogenesis have
      been profitably addressed.

PMID- 8305724
TI  - Flat embedding of microorganisms on slides with LR white for immunocytochemistry.

PMID- 8305725
TI  - New aspects of microvascular corrosion casting: a scanning, transmission
      electron, and high-resolution intravital video microscopic study.
AB  - We used intravital microscopy of small intestine and pancreas in order to show
      dynamic interactions between vascular wall and undiluted Mercox, because previous
      studies of ours have shown that Mercox diluted with monomeric methylmethacrylate
      penetrates cells in the vascular wall. Scanning and transmission electron
      microscopy were used to show three-dimensional pathways and correlating tissue
      structures, which cannot be identified in vivo. The microvascular diameters were
      not altered when the vasculature was flushed with saline/dextran solution using
      perfusion pressures between 70 and 140 mm Hg, but, in circumscribed areas,
      contraction of vascular wall was observed immediately after Mercox injection.
      This phenomenon was carried out by endothelial cells; pericytes were never
      present at the site of constrictions. Extravasation, i.e., leakage of the resin
      into the surrounding tissue, occurred in circumscribed areas regardless of the
      applied perfusion pressure. The resin also filled routes, which were not perfused
      with blood before casting. Scanning microscopy of corresponding specimens showed
      flattened cast channels, with impressions of valves and endothelial cell nuclear
      imprints characteristic of lymphatics. These results show that undiluted Mercox
      is a stimulus for vascular cellular components and that it changes the vascular
      wall permeability, resulting in extravasation and filling of lymphatics.
      Transmission electron microscopy showed that large vessels were homogeneously
      filled with resin and that cellular structures were not infiltrated with Mercox.
      Cut sections of the gold-coated surface of casts showed grooves up to 20 nm wide,
      suggestive of minimal deformation, while the abluminal surface of the metal film
      was almost smooth. Another proof of minimal deformation of undiluted Mercox casts
      is that the diameter of vessels was not altered during and after polymerization.
      Obtained casts are not fragile, as are casts of diluted Mercox, and phase
      separation does not occur, which would result in penetration of the cells in the
      vascular wall. For these reasons, the use of undiluted Mercox is recommended.
      Mixing 10 ml Mercox with 1 g catalyst resulted in complete polymerization within
      5.5-7 min. This mixture can be used for casting biological specimens.

PMID- 8305726
TI  - Comparison of hexamethyldisilazane (HMDS), Peldri II, and critical-point drying
      methods for scanning electron microscopy of biological specimens.
AB  - Three different drying methods, critical-point drying (CPD), Peldri II, and
      hexamethyldisilazane (HMDS), were compared using representative animal (rat
      kidney, trachea, duodenum, lung, and red blood cells) and plant (leaves from ten
      species of monocotyledons and dicotyledons) specimens. All three drying methods
      produced identical results with animal specimens. Plant specimens showed signs of
      shrinkage regardless of which drying method was employed. The order of
      preservation quality from best to worst for leaves was CPD > Peldri II > HMDS,
      with the CPD method providing substantially better results in all but one case.
      Postfixation of leaves with osmium tetroxide resulted in poorer preservation in
      all instances. Peldri II caused complete extraction of leaf cuticular wax, while
      both both CPD and HMDS showed minimal extraction compared with samples air dried
      directly from acetone. These results indicate that HMDS provides a time-saving
      and inexpensive alternative to CPD for animal specimens. Plant specimens,
      particularly those containing cells with large central vacuoles, are adequately
      preserved only with the CPD method. In addition, postfixation with osmium should
      be avoided when processing plant specimens for scanning electron microscopy.

PMID- 8305727
TI  - Artifacts caused by dehydration and epoxy embedding in transmission electron
      microscopy.
AB  - Epoxy resins are the principal embedding media for the preservation of tissues to
      be sectioned and examined by transmission electron microscopy. Their primary
      advantages are good ultrastructural preservation, little or no shrinkage, ease of
      sectioning, and reasonable stability in the electron beam. However, epoxy resins
      also have disadvantages; namely, some are toxic, they may mask antigenic sites to
      a greater extent than do some other embedding resins, and they do not penetrate
      tissues as well as less viscous embedding formulations. Some unusual
      characteristics may also be revealed, for example, as shrinkage of organelles, as
      problems in poststaining sections, and as movement of tissue elements within the
      block and section. Some of the properties of epoxy resins are discussed in this
      report.

PMID- 8305728
TI  - A method to detect areas high in sulfhydryl groups in mouse epithelium.
AB  - We have recently modified a non-fluorescent, non-radioactive histochemical method
      to detect sulfhydryl (S-H) groups in tissues. This method was originally intended
      to detect chloramphenicol acetyltransferase (CAT) in transgenic mice. Temporal
      developmental differences in the keratinization of mouse digits can be seen in
      the staining pattern of the skin about the toes of neonatal mice. The basal cells
      of the epidermis exposed to the air show intense staining while the epidermis
      that is still attached to an adjacent toe shows no staining. The degree of S-H
      presence can be determined by the tissues' resistance to blocking of the S-H
      groups by iodoacetic acid. Areas that contain very high numbers of S-H groups
      still show staining following blocking by iodoacetic acid. We have found that
      this method shows clear differences in the S-H distribution of various
      epithelium, including skin, hair, nails, and tongue epithelium.

PMID- 8305729
TI  - A novel cell culture technique for electron microscopy.
AB  - A simplified technique for the monolayer growth of cultured cells and their in
      situ embedment on the inner surface of the pyramidal portion of the Beem capsule
      for electron microscopy has been developed. The results demonstrated that the
      cell monolayers grew well on the surface of the Beem capsule and could be
      embedded in situ. Electron micrographs showed cells in their natural state of
      contact with one another. The plasma membrane and intracellular organelles were
      well preserved. This method minimizes many difficult steps and eliminates the
      disruption of cells by scraping, pelleting, or enzymatic reaction to remove them.

PMID- 8305730
TI  - The application of the OsO4 maceration method to the study of human bioptic
      material. A procedure avoiding freeze-fracture.

PMID- 8305731
TI  - p63cdc13, a B-type cyclin, is associated with both the nucleolar and chromatin
      domains of the fission yeast nucleus.
AB  - The cellular distribution of the fission yeast mitotic cyclin B, p63cdc13, was
      investigated by a combination of indirect immunofluorescence light microscopy,
      immunogold electron microscopy, and nuclear isolation and fractionation.
      Immunofluorescence microscopy of wild-type cells and the cold-sensitive mutant
      dis2.11 with a monospecific anti-p63cdc13 antiserum was consistent with the
      association of a major subpopulation of fission yeast M-phase protein kinase with
      the nucleolus. Immunogold electron microscopy of freeze-substituted wild-type
      cells identified two nuclear populations of p63cdc13, one associated with the
      nucleolus, the other with the chromatin domain. To investigate the cell cycle
      regulation of nuclear labeling, the mutant cdc25.22 was synchronized through
      mitosis by temperature arrest and release. Immunogold labeling of cells arrested
      at G2M revealed gold particles present abundantly over the nucleolus and less
      densely over the chromatin region of the nucleus. Small vesicles around the
      nucleus were also labeled by anti-p63cdc13, but few gold particles were detected
      over the cytoplasm. Labeling of all cell compartments declined to zero through
      mitosis. Cell fractionation confirmed that p63cdc13 was substantially enriched in
      both isolated nuclei and in a fraction containing small vesicles and organelles.
      p63cdc13 was not extracted from nuclei by treatment with RNase A, Nonidet P40 (NP
      40), Triton X-100, and 0.1 M NaCl, although partial solubilization was observed
      with DNase I and 1 M NaCl. A known nucleolar protein NOP1, partitioned in a
      similar manner to p63cdc13, as did p34cdc2, the other subunit of the M-phase
      protein kinase. We conclude that a major subpopulation of the fission yeast
      mitotic cyclin B is targeted to structural elements of the nucleus and nucleolus.

PMID- 8305732
TI  - Expression of NG2 proteoglycan causes retention of type VI collagen on the cell
      surface.
AB  - NG2 is a membrane-associated chondroitin sulfate proteoglycan with a core protein
      of 300 kD. Previously it was shown immunochemically that the core protein of NG2
      can bind type VI collagen (Stallcup, W., Dahlin, K., and P. Healy. 1990. J. Cell
      Biol. 111:3177-3188). We have extended our studies on the interaction of NG2 and
      type VI collagen by transfecting cells with the full-length rat NG2 cDNA. B28 rat
      neural cells and U251MG human glioma cells used for transfection do not
      synthesize NG2. Both cell lines secrete type VI collagen into tissue culture
      medium but do not anchor it at the cell surface. Upon transfection of these cells
      with the NG2 cDNA, NG2 was correctly localized to the cell surface. Furthermore,
      type VI collagen could now be detected on the surface of NG2-positive cells in a
      pattern that coincided with that of NG2. This ability of NG2 to anchor type VI
      collagen to the cell surface could be abolished by incubating the cells in the
      presence of anti-NG2 monoclonal antibodies. These findings indicate that NG2
      functions as a cell surface receptor for type VI collagen and may play a role in
      modulating the assembly of pericellular matrix.

PMID- 8305734
TI  - Autonomous replication of human chromosomal DNA fragments in human cells.
AB  - We have examined whether a human chromosome has distinct segments that can
      replicate autonomously as extrachromosomal elements. Human 293S cells were
      transfected with a set of human chromosomal DNA fragments of 8-15 kilobase pairs
      that were cloned on an Escherichia coli plasmid vector. The transfected cells
      were subsequently cultured in the presence of 5-bromodeoxyuridine during two cell
      generations, and several plasmid clones labeled in both of the daughter DNA
      strands were isolated. Efficiency of replication of these clones, as determined
      from the ratios of heavy-heavy and one-half of heavy-light molecules to total
      molecules recovered from density-labeled cells, was 9.4% per cell generation on
      the average. Replication efficiency of control clones excluded during the
      selection was about 2.2% and that of the vector plasmid alone was 0.3%. A
      representative clone p1W1 replicated in a semiconservative manner only one round
      during the S phase of the cell cycle. It replicated extrachromosomally without
      integration into chromosome. The human segment of the clone was composed of
      several subsegments that promoted autonomous replication at different
      efficiencies. Our results suggest that certain specific nucleotide sequences are
      involved in autonomous replication of human segments.

PMID- 8305733
TI  - The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein
      that binds immunoglobulin.
AB  - Anoxia, glucose starvation, calcium ionophore A23187, EDTA, glucosamine, and
      several other conditions that adversely affect the function of the endoplasmic
      reticulum (ER) induce the synthesis of the glucose-regulated class of stress
      proteins (GRPs). The primary GRPs induced by these stresses migrate at 78 and 94
      kDa (GRP78 and GRP94). In addition, another protein of approximately 150-170 kDa
      (GRP170) has been previously observed and is coordinately induced with GRP78 and
      GRP94. To characterize this novel stress protein, we have prepared an antisera
      against purified GRP170. Immunofluorescence, Endoglycosidase H sensitivity, and
      protease resistance of this protein in microsomes indicates that GRP170 is an ER
      lumenal glycoprotein retained in a pre-Golgi compartment. Immunoprecipitation of
      GRP170 with our antibody coprecipitates the GRP78 (also referred to as the B cell
      immunoglobulin-binding protein) and GRP94 members of this stress protein family
      in Chinese hamster ovary cells under stress conditions. ATP depletion, by
      immunoprecipitation in the presence of apyrase, does not affect the interaction
      between GRP78 and GRP170 but results in the coprecipitation of an unidentified 60
      kDa protein. In addition, GRP170 is found to be coprecipitated with
      immunoglobulin (Ig) in four different B cell hybridomas expressing surface IgM,
      cytoplasmic Ig light chain only, cytoplasmic Ig heavy chain only, or an antigen
      specific secreted IgG. In addition, in IgM surface expressing WEHI-231 B cells,
      anti-IgM coprecipitates GRP78, GRP94, as well as GRP170; antibodies against
      GRP170 and GRP94 reciprocally coprecipitate GRP94/GRP170 as well as GRP78.
      Results suggest that this 170-kDa GRP is a retained ER lumenal glycoprotein that
      is constitutively present and that may play a role in immunoglobulin folding and
      assembly in conjunction or consecutively with GRP78 and GRP94.

PMID- 8305735
TI  - Growth factor regulation of cyclin D1 mRNA expression through protein synthesis
      dependent and -independent mechanisms.
AB  - Overexpression of the cyclin D1/PRAD1 oncogene has been observed in a number of
      tumorigenic cell lines, suggesting that regulation of D1 expression may represent
      an important step in the control of cellular proliferation. We have examined the
      mRNA expression of cyclin D1, as well as two related D-type cyclins, D2 and D3,
      in response to defined growth factors that control the growth of Balb/c-3T3
      fibroblasts. Transcripts for all three D-type cyclins were expressed during the
      G1 phase of the Balb cell cycle, however only D1 and D3 exhibited periodic
      induction. Although redundantly expressed, message levels of cyclin D1 and D3
      were differentially regulated in regard to kinetics of induction; a modest
      increase in D3 mRNA was detected near the G1/S boundary, 12 h after serum
      stimulation of quiescent cells, while abundance of D1 transcript increased 20 to
      30-fold, peaking 6 h after addition of serum. Factors such as platelet-derived
      growth factor (PDGF) that induce competence formation in Balb cells, increased D1
      message and protein levels to the same extent as serum but did not affect
      expression of cyclin D3 and did not stimulate entry into S phase. Progression
      factors contained within platelet-poor plasma stimulated D1 expression only
      weakly but acted synergistically with low concentrations of PDGF to increase D1
      mRNA to maximum levels. Depletion of protein kinase C severely reduced the
      ability of PDGF and serum to induce D1 mRNA. PDGF- and serum-mediated elevation
      of steady-state D1 message levels was in part because of a transcriptional
      activation of the D1 gene that was independent of protein synthesis. However,
      protein synthesis was required 3-4 h after serum stimulation for the shut down of
      D1 transcription leading to the normal decline in message levels after peak
      induction. Our results indicate that overexpression of cyclin D1 message may
      result from a disruption of negative regulatory events that repress D1
      transcription.

PMID- 8305736
TI  - Genetic interactions between KAR2 and SEC63, encoding eukaryotic homologues of
      DnaK and DnaJ in the endoplasmic reticulum.
AB  - KAR2 encodes the yeast homologue of mammalian BiP, the endoplasmic reticulum (ER)
      resident member of the HSP70 family. Kar2p has been shown to be required for the
      translocation of proteins across the ER membrane as well as nuclear fusion.
      Sec63, an ER integral membrane protein that shares homology with the Escherichia
      coli DnaJ protein, is also required for translocation. In this paper we describe
      several specific genetic interactions between these two proteins, Kar2p and
      Sec63p. First, temperature-sensitive mutations in KAR2 and SEC63 form synthetic
      lethal combinations. Second, dominant mutations in KAR2 are allele-specific
      suppressors for the temperature-sensitive growth and translocation defect of
      sec63-1. Third, the sec63-1, unlike other translocation defective mutations,
      results in the induction of KAR2 mRNA levels. Taken together, these genetic
      interactions suggest that Kar2p and Sec63p interact in vivo in a manner similar
      to that of the E. coli HSP70, DnaK, and DnaJ. We propose that the interaction
      between these two proteins is critical to their function in protein
      translocation.

PMID- 8305737
TI  - The three rows gene of Drosophila melanogaster encodes a novel protein that is
      required for chromosome disjunction during mitosis.
AB  - Zygotic expression of the three rows (thr) gene of Drosophila melanogaster is
      required for normal cell proliferation during embryogenesis. Mitotic defects in
      thr mutant embryos begin during mitosis 15, and all subsequent divisions are
      disrupted. Chromosome disjunction and consequently cytokinesis fail during these
      defective mitoses, although the initial mitotic processes (chromosome
      condensation, spindle assembly, metaphase plate formation, and cyclin
      degradation) are not affected. Despite the failure of chromosome disjunction and
      cytokinesis, later mitotic events (chromosome decondensation) and subsequent cell
      cycle progression continue. The thr gene has been isolated and shown to encode a
      1209 amino acid protein that shares no extended sequence similarity with known
      proteins. thr mRNA is present as maternal mRNA that degrades at the time of
      cellularization. At this and all subsequent times during embryogenesis, zygotic
      expression correlates with mitotic proliferation. These observations, together
      with the observation that the zygotic phenotype of thr mutant embryos is
      influenced by the maternal genotype, suggest that the embryonic phenotype results
      from exhaustion of the maternal thr contribution and does not reflect a
      developmentally restricted requirement for thr function. Our results indicate
      that the novel thr product is required specifically for chromosome disjunction
      during all mitoses.

PMID- 8305738
TI  - The human GRB2 and Drosophila Drk genes can functionally replace the
      Caenorhabditis elegans cell signaling gene sem-5.
AB  - Mutations in the Caenorhabditis elegans gene sem-5 affect cell signaling
      processes involved in guiding a class of cell migrations and inducing vulval cell
      fates. The sem-5 sequence encodes a protein comprised almost exclusively of SH2
      and SH3 domains (SH, src homology region) that are found together in many
      signaling proteins and nonreceptor tyrosine kinases. A human protein, GRB2, was
      identified by its ability to associate with the activated human epidermal growth
      factor receptor (hEGFR). The GRB2 and Sem-5 proteins share an identical
      architecture of their SH2 and SH3 domains and 58% amino acid sequence identity.
      Here we demonstrate that GRB2 and a Drosophila sem-5-like gene Drk can
      specifically rescue sem-5 mutants. We also show that Sem-5, like GRB2, can bind
      to the activated hEGFR in vitro. We further correlate the abilities of several
      mutant variants of GRB2 and Sem-5 to bind to the hEGFR in vitro with their
      abilities to functionally replace sem-5 in vivo. These data indicate that GRB2
      and Drk are functional homologues of Sem-5 and demonstrate the high degree of
      conservation of both structure and function between signaling systems throughout
      evolution.

PMID- 8305739
TI  - Mediation of NGF-stimulated extracellular matrix invasion by the human melanoma
      low-affinity p75 neurotrophin receptor: melanoma p75 functions independently of
      trkA.
AB  - Although overexpression of the low-affinity p75 neurotrophin receptor (p75NTR) is
      frequently associated with advanced stages of human melanoma progression, the
      functional significance of this finding is unknown. We examined whether the
      degree of cell surface expression of p75NTR in human melanoma cell variants
      determines their extent of invasion stimulated by nerve growth factor (NGF).
      Treatment of MeWo melanoma cells or a metastatic spontaneous wheat germ
      agglutinin-resistant variant subline (70W) of MeWo cells with 2.5S NGF resulted
      in a dose-dependent enhancement of invasion through a reconstituted basement
      membrane. This effect was most pronounced with the 70W subline that exhibits
      brain-metastasizing potential in nude mice but was not found with a poorly
      metastatic MeWo variant subline (3S5). The expression of p75NTR as determined by
      Northern blotting and immunoprecipitation analysis of 125I-labeled cell surface
      proteins correlated with NGF-stimulated invasion. The MeWo melanoma sublines used
      in this study did not express p140proto-trkA mRNA or any p140proto-trkA variant
      transcripts including p70trkA as determined by Northern analysis and RT-PCR
      analysis. Thus, these melanoma cells would not be expected to form functional p75
      p140 heterodimers or p140-p140 homodimers capable of transducing an NGF-generated
      signal to p140proto-trkA cytoplasmic substrates. These cells did express
      authentic p145trkC transcripts. However, NGF did not catalytically activate
      p145trkC receptors via increased tyrosine phosphorylation as would be expected if
      p145trkC participated in the signaling established by NGF. Furthermore, a NGF
      stimulated purine-analogue-sensitive kinase activity was found to
      coimmunoprecipitate with p75NTR. This p75NTR-associated kinase may coordinate
      initial signaling events evoked by p75NTR ligand interaction. Addition of 2.5S
      NGF, at concentrations that should saturate cell surface p75NTR, to matrix
      adherent cultures of human MeWo and 70W but not 3S5 melanoma cells suppressed the
      expression of 92-kDa type IV collagenase and stimulated the production of 72-kDa
      type IV collagenase in its fully active 68-kDa form. In the absence of p140proto
      trkA, the matrix-dependent effects of NGF on metalloproteinase expression of
      brain-metastatic 70W melanoma cells suggest a signaling role for the low-affinity
      melanoma p75NTR receptor and its associated purine-analogue-sensitive kinase in
      signaling enhanced matrix penetration of NGF-rich stromal microenvironments such
      as the brain.

PMID- 8305740
TI  - Regulation of NADPH oxidase activity by Rac GTPase activating protein(s).
AB  - Activation of the NADPH oxidase of phagocytic cells requires the action of Rac2
      or Rac1, members of the Ras superfamily of GTP-binding proteins. Rac proteins are
      active when in the GTP-bound form and can be regulated by a variety of proteins
      that modulate the exchange of GDP for GTP and/or GTP hydrolysis. The p190 Rac
      GTPase Activating Protein (GAP) inhibits human neutrophil NADPH oxidase activity
      in a cell-free assay system with a K1 of approximately 100 nM. Inhibition by p190
      was prevented by GTP gamma S, a nonhydrolyzable analogue of GTP. Similar
      inhibition was seen with a second protein exhibiting Rac GAP activity, CDC42Hs
      GAP. The effect of p190 on superoxide (O2-) formation was reversed by the
      addition of a constitutively GTP-bound Rac2 mutant or Rac1-GTP gamma S but not by
      RhoA-GTP gamma S. Addition of p190 to an activated oxidase produced no inhibitory
      effect, suggesting either that p190 no longer has access to Rac in the assembled
      oxidase or that Rac-GTP is not required for activity once O2- generation has been
      initiated. These data confirm the role of Rac in NADPH oxidase regulation and
      support the view that it is the GTP form of Rac that is necessary for oxidase
      activation. Finally, they raise the possibility that NADPH oxidase may be
      regulated by the action of GAPs for Rac proteins.

PMID- 8305741
TI  - Tiazofurin decreases Ras-GTP complex in K562 cells.
AB  - The ras oncogene product (p21ras, Ras) is a GTP-binding protein and is thought to
      transduce signals regulating cellular proliferation and differentiation. The
      active form Ras-GTP is inactivated by hydrolyzing bound GTP to GDP. Tiazofurin, a
      specific inhibitor of IMP dehydrogenase, decreased cellular GTP pools and
      downregulated c-ras gene expression, leading to differentiation (Olah, E. et al.,
      Proc. Natl. Acad. Sci. USA 85: 6533-6537, 1988; Weber et al., Cancer Commun. 3:61
      66, 1991). To clarify the link between the action of tiazofurin on metabolic
      alterations and the induction of differentiation, we examined the effect of
      tiazofurin on the ratio of active Ras-GTP to total Ras in K562 cells in culture.
      Cells were labeled for 6 h with [32P]Pi in phosphate-free RPMI 1640. Tiazofurin
      (100 or 200 microM) was added to cells, and samples were taken at 0, 2, 4, 6 and
      12 h of incubation. Cell lysates were immunoprecipitated with monoclonal anti-p21
      antibody (Y13-259), then developed on thin layer chromatography. GTP and GDP
      bound to Ras were visualized by autoradiography. Tiazofurin treatment decreased
      Ras-GTP concentration in a time- and dose-dependent fashion. In the untreated
      K562 cells the Ras-GTP concentration was 26.3 +/- 1.4, and tiazofurin (200
      microM) decreased it at 6 h to 16.6 +/- 2.9 and at 12 h to 10.6 +/- 2.1%.
      Inhibition of the GTP salvage pathway with hypoxanthine (100 or 200 microM)
      enhanced the tiazofurin-induced decrease of Ras-GTP, whereas addition of
      guanosine (100 microM) prevented the Ras-GTP decrease.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8305742
TI  - Interconversion and stability of duocarmycins, a new family of antitumor
      antibiotics: correlation to their cytotoxic and antimicrobial activities in
      vitro.
AB  - Stability and interconversion of duocarmycins were studied in relation to their
      cytotoxicities and antimicrobial activities. The compounds studied included
      duocarmycin A and SA, which have a spirocyclopropylhexadienone moiety, and four
      halogenated seco-compounds of duocarmycin A: duocarmycin B1, B2, C1 and C2, from
      which the cyclopropane ring structure is absent. Duocarmycins were potent
      cytotoxic compounds to cells. The cytotoxic activity seen on Balb 3T3/H-ras cells
      after 72 h drug exposure was in the following order (IC50 (nM): concentration for
      50% growth inhibition); SA (0.05) > A (0.3) > B2 (1.5) > B1 (3.0) > C2 (20) > C1
      (40). Average minimum inhibitory concentrations (MICs) of duocarmycins against
      microorganisms showed essentially the same ranking order as that of cytotoxicity.
      There was a large difference between SA and A in their stability in aqueous
      solvents. For halogenated seco-compounds, a good correlation was found between
      their cytotoxicities in vitro and their conversion rate to duocarmycin A,
      suggesting that halogenated seco-compounds undergo closure to the
      spirocyclopropylhexadienone structure, the pertinent active form, in cells.

PMID- 8305743
TI  - Effects of sodium butyrate, dimethylsulfoxide and dibutyryl cAMP on the poorly
      differentiated ovarian adenocarcinoma cell line AMOC-2.
AB  - To determine whether the poorly differentiated AMOC-2 human ovarian
      adenocarcinoma cell line was capable of undergoing differentiation, AMOC-2 cells
      were exposed to 2 mM sodium butyrate, 2.5% dimethylsulfoxide, or 4 mM dibutyryl
      cyclic adenosine monophosphate (dibutyryl cAMP) for 6 days. These treatments
      resulted in growth inhibition, a reduction in clonogenicity and an increase in
      cellular glycogen content. Significant increases in heat stable alkaline
      phosphatase activity also occurred after exposure to sodium butyrate. In
      addition, a thorn-like microfilament structure observed in untreated cells was
      diminished concomitantly with morphological changes that included flattening,
      enlargement and extended cytoplasmic processes after exposure to sodium butyrate
      or dibutyryl cAMP. Furthermore, treatment with sodium butyrate increased the
      intracellular concentrations of beta-tubulin, vimentin, neurofilaments (M(r)
      210,000) and cytokeratin (M(r) 56,000-58,000). These changes were completely
      reversed after removal of the inducing agent. The findings suggest that treatment
      of AMOC-2 cells with sodium butyrate induced a more differentiated phenotype,
      although terminal differentiation was not achieved.

PMID- 8305744
TI  - The effect of thrombospondin on invasion of fibrin gels by human A549 lung
      carcinoma.
AB  - Thrombospondin (TSP) was evaluated for its effect on the capacity of human A549
      lung adenocarcinoma cells to invade and degrade fibrin gels. Cells suspended in
      DMEM containing 0.01 units/mL plasminogen were added to a 2.5 mm diameter well in
      a 2 mm thick fibrin gel. Various concentrations of TSP were added either to the
      cells or to the gel. After 18 hours, the number of spread and gel-adherent cells
      were counted and the diameter of the well was measured to determine the extent of
      tumor-induced fibrinolysis. In the absence of TSP, the tumor cells were non
      adherent but catalyzed the rapid degradation of the fibrin gel, causing the
      application well to increase in diameter several-fold. In contrast, addition of
      either TSP to the gel or to the cell suspension inhibited fibrinolysis in a dose
      dependent manner and promoted attachment and spreading of cells in the fibrin
      matrix. In contrast, fibronectin had no effect. The effect of TSP on both tumor
      cell-associated fibrinolysis and cell adhesion was inhibited with an anti-TSP
      monoclonal antibody. The cell adhesive peptides CSVTCG, derived from the type 1
      repeats of TSP, and GRGDS also had no effect on tumor cell-associated
      fibrinolysis. TSP inhibited fibrinolysis by inhibiting tumor cell-secreted
      urokinase activity, but had no effect on total urokinase secreted-antigen. In
      contrast, cell-associated urokinase activity was protected from inhibition by
      TSP. These results suggest that TSP may promote tumor cell metastasis not only by
      promoting cell-attachment but also by protecting tumor cell-fibrin emboli from
      degradation by tumor secreted- and host fibrinolytic enzymes.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8305745
TI  - Deoxycytidine kinase and thymidine kinase activities in rat brain.
AB  - Deoxycytidine (CdR) kinase (E.C. 2.7.1.74) acts as a salvage enzyme in DNA
      biosynthesis, but little is known about this important nucleoside kinase in the
      brain. We report that CdR kinase activity in the 100,000 x g cytosolic fraction
      of normal adult rat brain cortex was 0.89 +/- 0.04 nmol/hr/mg protein which is
      twice that of the liver enzyme. For brain CdR kinase the apparent Km for CdR, ATP
      and Mg++ were 0.22, 1.1 and 0.63 mM, respectively. When the cytosolic preparation
      was incubated at 37 degrees C, CdR kinase activity rapidly decreased (t1/2 = 15
      min); CdR (400 microM) protected the enzyme. Addition of DFDC (0 to 100 microM)
      competitively inhibited brain CdR kinase activity with Ki = 17 microM. DFDC
      elevated the apparent Km for CdR of brain CdR kinase 3.5-fold, from 0.22 to 0.8
      mM. DFDC did not inhibit brain TdR kinase. AZT, which competitively inhibited TdR
      kinase (Ki = 0.6 microM), did not affect brain CdR kinase activity. These results
      indicate that the cytosol of rat brain contains CdR kinase which is inhibited by
      the deoxycytidine analog, DFDC. The enzyme is protected from thermal denaturation
      by CdR but not by TdR.

PMID- 8305746
TI  - Reference listings in cancer research.

PMID- 8305747
TI  - Peroxisome disorders and cutaneous manifestations.

PMID- 8305748
TI  - Metabolism and degradation of betamethasone 17-valerate in homogenized living
      skin equivalent.
AB  - The metabolism of betamethasone 17-valerate was estimated using an artificial
      living skin equivalent (LSE). Betamethasone 17-valerate, betamethasone 21
      valerate and betamethasone were measured by a normal-phase high-performance
      liquid chromatographic (HPLC) method. Betamethasone 17-valerate was added to the
      culture medium with or without LSE homogenate. Degradation profiles (%) of
      betamethasone 17-valerate remaining in the culture medium with skin homogenate
      did not differ from those without homogenate. However, the conversion of
      betamethasone 21-valerate to betamethasone was accelerated by skin homogenate,
      indicating that LSE has a sufficient level of esterase.

PMID- 8305749
TI  - Epicutaneous test in carbamazepine cutaneous reactions.
AB  - Carbamazepine is a widely used drug associated with numerous side effects
      including skin eruptions that appear in about 4% of patients. Epicutaneous tests
      have been used with variable success in skin drug reactions. The purpose of this
      study was to work out the efficacy of this type of test in carbamazepine
      reactions. Five patients with carbamazepine cutaneous reaction were studied.
      Clinical, laboratory and histopathological data were recorded. The 5 patients and
      20 controls were tested with carbamazepine 1% in petrolatum. In 4 patients the
      carbamazepine epicutaneous test was positive. The 20 healthy controls were
      negative. Epicutaneous testing is a simple and helpful method in detecting
      carbamazepine hypersensitivity.

PMID- 8305750
TI  - Terminal differentiation of facial epidermis of the aged: immunohistochemical
      studies.
AB  - In old age, the epidermis tends to become dry and flaky, especially on the lower
      legs. However, this does not occur on the face, although long-term ultraviolet
      light irradiation has important effects on the differentiation of facial
      keratinocytes. Therefore, the differentiation of the epidermal cells of the
      facial skin in the young and the aged was immunohistochemically examined using
      antibodies against four differentiation products: filaggrin, involucrin, cystatin
      A (CTA) and carbonic anhydrase-like protein. The results showed that there was no
      difference in the amounts of the above three proteins in facial skin between the
      young and the aged with the exception of CTA. The amount of CTA was much greater
      in the facial skin of the aged. However, there was a striking decrease of
      filaggrin content in the skin of the lower leg in the aged. One of the reasons
      why no scaly skin is found on the face in the aged may be the fact that
      especially filaggrin does not decrease with aging.

PMID- 8305751
TI  - Adrenoleucodystrophy: dermatological findings and skin surface lipid study.
AB  - X-linked adrenoleucodystrophy (ALD) is a rare disorder of the very-long-chain
      fatty acid (VLCFA) metabolism. Cutaneous findings observed in a 29-year-old man
      included patchy non-cicatricial alopecia of the scalp, intense oily seborrhoea of
      the head, mild dry-scaling ichthyosis-like appearance of the trunk and legs and
      pseudo-acanthosis nigricans of the folds. Scanning electron-microscopic
      examination of the scalp hair showed trichorrhexis-nodosa-like fractures and
      several structural anomalies of the hair shaft. The skin surface lipid profile
      showed a marked increase in lignoceric acid (C24:0) which comprised over 60% of
      the fatty acid detectable in the fractions of triglycerides, diglycerides and
      free fatty acids. This behaviour of the VLCFA in the surface lipids corresponds
      to that observed in the plasma. If this finding were confirmed, the investigation
      of surface lipid composition could represent a useful non-invasive technique for
      the study of ALD.

PMID- 8305752
TI  - Marginal papular acrokeratodermas: a unified nosography for focal acral
      hyperkeratosis, acrokeratoelastoidosis and related disorders.
AB  - Several entities, quite often similar, share keratotic papules, usually
      crateriform, along the border of the hands and feet as a common clinical finding.
      These conditions are acrokeratoelastoidosis of Costa, focal acral hyperkeratosis,
      acrokeratoelastoidosis of Matthews and Harman, mosaic acral keratosis, hereditary
      papulotranslucent acrokeratoderma, acrokeratoderma hereditarium punctatum,
      degenerative collagenous plaques of the hands, keratoelastoidosis marginalis and
      digital papular calcinosis. We describe two further cases of focal acral
      hyperkeratosis in two Caucasian women, review the clinical and histological
      features of the related conditions and suggest that some are variants of the same
      entity. We propose the simplified concept of marginal papular acrokeratodermas
      that may be divided into (1) the hereditary type (subdivided into that with and
      without elastorrhexis) and (2) the acquired type.

PMID- 8305753
TI  - Chronic fatigue syndrome: a novel disorder with cutaneous manifestations.
AB  - Persistent and disabling fatigue associated with low-grade fever and other
      constitutional symptoms, without any known disorder that accounts for it, is
      recognized as chronic fatigue syndrome (CFS). Skin lesions occur in 10-35% of
      patients, but their description is inaccurate. Recurrent aphthous stomatitis or
      persistent Epstein-Barr virus (EBV)-related erythema multiforme have also been
      reported. Patients may be diagnosed as having CFS only when they fulfill at least
      2 major and 8 minor criteria. Major criteria are the presence of debilitating
      fatigue persisting or recurring for at least 6 months and the absence of any
      other medical disorder that may explain it. Although different viral or nonviral
      etiologies have been documented, evidence implicating EBV is gaining support.

PMID- 8305754
TI  - EMLA-induced analgesia inferior to lignocaine infiltration in curettage of common
      warts--a randomized study.
AB  - The analgesic effect of topical application of EMLA cream for the curettage
      verrucae vulgaris was compared to local infiltration with lignocaine in 89
      patients. The main purpose of this randomized study was to evaluate the patients'
      overall impression of the treatment. All patients anaesthetized by lignocaine
      infiltration reported it as 'an acceptable procedure' compared to only 71% of the
      patients treated with EMLA. It cannot be recommended to use EMLA cream as local
      anaesthetic for curettage of verrucae vulgaris, presumably because the highly
      keratotic nature of the common warts does not allow sufficient penetration of
      epicutaneously applied EMLA.

PMID- 8305755
TI  - Squamous cell carcinoma complicating lichen planus: a clinico-pathological study
      of three cases.
AB  - Squamous cell carcinoma complicating lichen planus is described in 3 patients. In
      2, the cancers developed on the lower leg in chronic and hypertrophic lichen
      planus. In the other case, the cancer complicated lichen planus of the lip mucosa
      in a smoker. In the two cutaneous cases, the tumour and the adjacent skin showed
      features of lichen planus, including hypergranulosis, cytoid bodies and a
      lichenoid infiltrate. The association, though rare with cutaneous lichen planus
      when it tends to affect chronic hypertrophic lesions on the lower legs, is now
      well recognized with oral lichen planus. Patients with oral involvement warrant
      long-term follow-up, especially if they have other risk factors such as smoking
      or excessive ultraviolet exposure. Chronicity of lichen planus at other skin
      sites may also be a risk factor.

PMID- 8305756
TI  - A case of congenital reticular ichthyosiform erythroderma--ichthyosis 'en
      confettis'.
AB  - We describe the third case of congenital reticular ichthyosiform erythroderma
      (CRIE), a rare inherited keratinization disorder, the second with the peculiar
      reticulate skin pattern. The same case had been previously described and defined,
      for the clinical appearance, as ichthyosis 'en confettis'. An 18-year-old girl
      was born with the clinical features of an erythrodermic lamellar ichthyosis.
      Patches of normal skin enclosed by erythematous-ichthyotic skin in a reticular
      arrangement appeared on the trunk at the age of 10 years, and they enlarged
      slowly during 6 years. The treatment with etretinate, started 2 years ago,
      further increased this process. Another peculiar clinical feature is a remarkable
      hypertrichosis. At the ultrastructural level, perinuclear deposits of filamentous
      material in vacuolized keratinocytes of the upper epidermis, pathognomonic for
      CRIE, were demonstrated. This suggests that CRIE and ichthyosis 'en confettis'
      are the same disorder. In addition the peculiar clinical presentation of this
      rare genodermatosis develops only during late childhood and puberty. The
      identification of three sporadic cases only leaves the problem of inheritance
      still unsolved.

PMID- 8305757
TI  - Prenatal diagnosis of epidermolysis bullosa: first successful trial in Asia.
AB  - Prenatal diagnosis of epidermolysis bullosa (EB) using fetal skin biopsy
      specimens has been successfully performed in Europe and America, but this
      technique has not previously been attempted in Asia. For the first time in Asia,
      we attempted to make a prenatal diagnosis of EB in a high-risk fetus by fetal
      skin biopsy. A skin biopsy was obtained from the fetus at risk of gravis type
      junctional epidermolysis bullosa of Herlitz. The biopsy specimen was studied by
      electron microscopy and immunohistochemistry using various monoclonal antibodies
      against the epidermal basement membrane zone (BMZ). There were no ultrastructural
      abnormalities in the BMZ, including the hemidesmosomes. Indirect
      immunofluorescence showed normal expression of GB3 antigen. The pregnancy was
      continued, and a normal, healthy infant was born. The prenatal diagnosis of
      epidermolysis bullosa is now available in Tokyo. This clinical diagnostic service
      is available to families from various parts of Asia.

PMID- 8305758
TI  - Specific xerostomia during Urbach-Wiethe disease.
AB  - We describe the case of a 59-year-old woman who had suffered from a typical
      Urbach-Wiethe disease since childhood and who complains of progressive mouth and
      ocular dryness since the age of 54 years. Xerostomia was severe with very poor
      salivation and was associated with a slight keratoconjunctivitis sicca. A
      specific lipoid proteinosis was evidenced in salivary glands (lower lip biopsy)
      with a PAS-positive hyalin-like deposit around vessels, capillaries and salivary
      gland canaliculi. An ultrastructural study showed the typical aspect of
      multilamination of the basal lamina of capillary vessels. Dysphonia and
      hoarseness are commonly found in Urbach-Wiethe disease, but, to our knowledge, a
      specific xerostomia has never been reported.

PMID- 8305759
TI  - Ki-1-positive anaplastic large cell lymphoma with different phenotypes in skin
      nodules and lymph nodes.
AB  - A 54-year-old man had lymph node swelling and skin nodules. Neoplastic cells with
      pleomorphic nuclei, prominent eosinophilic nucleoli and abundant cytoplasm were
      present in the lymph node sinuses and around the dermal appendages. Neoplastic
      cells in the lymph nodes expressed Ber-H2 (CD30)+/KP1 (CD68)+/MAC387-/LN-5+.
      Those in the skin nodules expressed Ber-H2+/KP1-/MAC387+/LN-5-. These findings
      suggest that he had Ki-1-positive anaplastic large cell lymphoma (ALCL) with
      different phenotypes in lymph nodes and skin nodules. The discrepancy among KP1,
      MAC387 and LN-5 reactivities may represent the concurrent occurrence of ALCL and
      lymphomatoid papulosis. However, the possibility cannot be ruled out that ALCL
      developed first in the lymph nodes and then metastasized to the skin.

PMID- 8305760
TI  - Malignant transformation of benign hidroacanthoma simplex.
AB  - A case of malignant hidroacanthoma simplex of the anterior aspect of the right
      ankle in a 75-year-old man is reported. A specimen obtained in 1987 showed the
      features of benign hidroacanthoma simplex, whereas that taken in 1991 revealed
      malignant transformation. We performed immunohistochemical studies on these two
      specimens, and they suggest this tumor derives from the outer cells of
      intraepidermal ducts. The proliferating cell nuclear antigen labelling index and
      argyrophil nucleolar organizer regions of these two specimens were also compared
      and correlated with malignant transformation.

PMID- 8305761
TI  - Human keratinocytes make uniquely linear phagokinetic tracks.
AB  - The migration of human keratinocytes is dramatically influenced by the type of
      extracellular matrix in contact with the cells: collagen induces the cells to
      produce long, linear migration tracks. In this study, a migration assay and
      computer-assisted morphometry were used to quantitate the extent of migration and
      the linearity of the migration tracks for a variety of cell types. Only human
      keratinocytes and HT-1080 fibrosarcoma cells produced both high levels of
      migration (migration index > 30) and highly linear tracks (track linearity >
      4.5). Human keratinocytes and HT-1080 cells share at least two other features:
      both synthesize copious amounts of extracellular matrix components, and both
      synthesize high levels of collagenase that degrades basement membrane (type IV)
      collagen. However, zymogram studies of collagenase production do not yield any
      characteristic collagenase profile which might distinguish these two types of
      cells from other normal and metastatic cells.

PMID- 8305762
TI  - Neurocutaneous melanosis.
AB  - A case of neurocutaneous melanosis with malignant leptomeningeal melanoma is
      reported in a 50-year-old white woman. The case is exceptional as regards the
      late onset of symptoms and death. Although the association of extracutaneous
      melanomas with cutaneous pigmented lesions is rare, dermatologists must be aware
      of their presence.

PMID- 8305763
TI  - Oral mucosa malignant melanoma in situ with involvement of the perioral skin.
AB  - A 66-year-old Japanese woman had a pigmented macule spreading from the internal
      aspect of the cheek to the vermilion border and perioral skin. Histology was that
      of in situ malignant melanoma. This case appears to be unique as it implies a
      longer period of radial growth than is usually observed in malignant melanoma of
      the oral mucosa.

PMID- 8305764
TI  - A case of skin metastasis from follicular thyroid carcinoma.
AB  - We present a case of skin metastasis from follicular thyroid carcinoma which
      developed on the scalp of a 72-year-old man. The lesion was noticed 1 month after
      a surgical excision of the primary thyroid carcinoma and gradually enlarged
      during the past 11 months. A biopsy from the nodule showed mostly well
      differentiated thyroid follicular structures with colloid material. Tumor cells
      showed mild variation of nuclear size and shape in almost all areas. We performed
      immunohistochemistry using antithyroglobulin antibody, which established the
      diagnosis of a metastatic lesion from thyroid follicular carcinoma. Total
      thyroidectomy and 131I radiotherapy were performed. No further metastasis has
      been discovered during the last 18 months.

PMID- 8305765
TI  - Isolated congenital atrichia in an Omani kindred.
AB  - Congenital atrichia may occur isolated or with associated defects. The isolated
      variant is especially uncommon. Sporadic and familial cases have been rarely
      reported. We present a large inbred kindred from Oman where 22 affected members
      with this disorder were found over six generations. The male-to-female ratio was
      1:1.4. No associated ectodermal or other defects were noted. A typical autosomal
      recessive mode of inheritance was documented. Though inbreeding was high,
      anticipated quasidominance was observed only once.

PMID- 8305766
TI  - Kaposi's sarcoma and monoclonal gammopathy.

PMID- 8305767
TI  - The MNSs and Kk blood group systems in the disease of Mljet (mal de Meleda)

PMID- 8305768
TI  - Raynaud's phenomenon with incomplete features of scleroderma: a wolf in sheep's
      clothing and a possible new indication for pulmonary/heart graft.

PMID- 8305769
TI  - Rapid determination of maintenance heparin infusion rates with the use of non
      steady-state heparin concentrations.
AB  - OBJECTIVE: To compare heparin dosage adjustment using only activated partial
      thromboplastin time (APTT) with a method using non-steady-state heparin
      concentrations (HCs) to rapidly achieve and maintain an APTT ratio greater than
      or equal to 1.5 times baseline throughout the first 24 hours of therapy. DESIGN:
      Randomized, blind, parallel comparison of an empiric dosing method based only on
      APTT with a dosing method based on the calculation of heparin clearance using non
      steady-state HCs. SETTING: A private community teaching hospital. The patient,
      physician, nurses, and investigators were blinded to the dosing method. Only the
      clinical staff pharmacist, who received the consult and made all dosage
      adjustments, was not blinded. PATIENTS: All patients requiring heparin for the
      treatment of thromboembolic disease were evaluated for potential inclusion in the
      study. Patients were enrolled in the study if they had a clinical diagnosis of
      deep venous thrombosis confirmed by objective means such as venography or
      ultrasonography. Patients were excluded if they had active bleeding, platelet
      dysfunction, thrombocytopenia, severe hepatic disease (total bilirubin > 25.7
      mumol/L), renal disease, or evidence of stroke. Patients were also excluded if
      they were receiving heparin prior to enrollment. MAIN OUTCOME MEASURE:
      Maintenance of an APTT ratio greater than or equal to 1.5 times baseline
      throughout the first 24 hours of heparin therapy. RESULTS: Thirty-four patients
      were enrolled in the study; 17 in each group. The groups were not significantly
      different with regard to gender, age, baseline APTT, or mean loading dose (p >
      0.5). Mean initial infusion rates for the control and HC groups were 1042 +/- 194
      and 1071 +/- 143 units/h, respectively (p > 0.5). After the first rate adjustment
      at 4 hours, the difference achieved significance at 1032 +/- 232 and 1367 +/- 317
      units/h for the control and HC groups, respectively (p < 0.01). At 12 hours, 18.8
      percent of the patients in the control group were subtherapeutic; by 24 hours,
      33.3 percent were subtherapeutic. No patients became subtherapeutic in the HCs
      group during the first 24 hours. CONCLUSIONS: This study demonstrates that, in
      contrast to standard heparin dosing methods, the use of non-steady-state HCs
      allows patients with deep venous thrombosis to rapidly achieve and maintain
      therapeutic APTT ratios throughout the critical first 24 hours of therapy.

PMID- 8305770
TI  - Bioequivalence of two methotrexate formulations in psoriatic and cancer patients.
AB  - OBJECTIVE: To compare the bioequivalence of a generic methotrexate (MTX) tablet
      (Mylan) with that of a brand-name (Lederle) product. DESIGN: A single-dose,
      randomized, crossover study. SETTING: Clinical Research Center (CRC) at a
      university hospital. PATIENTS: Men and women who had a diagnosis of malignancy or
      psoriasis who were at least 21 years old. METHODOLOGY: Two overnight study
      periods were scheduled at the CRC at least one week, but not more than two weeks
      apart. Each period consisted of a 10-hour fast prior to and 4 hours following
      oral MTX 15 mg administered as six 2.5-mg tablets. Blood samples were collected
      over 48 hours. Plasma MTX concentrations were determined using an HPLC assay.
      Area under the curve from zero to infinity (AUC0-infinity) was calculated by the
      log-trapezoidal method. RESULTS: Twenty-two patients (21 psoriasis, 1 colon
      cancer) aged 23-61 years completed both study periods. Mean values for peak
      concentration, time to peak concentration, and AUC0-infinity were 0.80 mumol/L,
      1.2 hours, and 3.0 mumol.h/L, respectively, for Mylan's MTX tablets and 0.81
      mumol/L, 1.4 hours, 3.0 mumol.h/L, respectively, for Lederle's MTX. Normalization
      for weight or body surface area did not affect interpatient variability. Relative
      bioavailability of generic MTX was 99.2 percent. Rate and extent of absorption
      were not significantly different and the confidence intervals were within the
      range of 80-120 percent required by the Food and Drug Administration.
      CONCLUSIONS: Mylan's MTX tablet is bioequivalent to Lederle's product.

PMID- 8305771
TI  - Measured versus estimated creatinine clearance in patients with low serum
      creatinine values.
AB  - OBJECTIVE: To examine, in patients with a serum creatinine (SCr) < 85 mumol/L,
      whether the use of actual SCr versus the use of an SCr set at 85 mumol/L and
      applied to the Cockcroft-Gault method for calculation of creatinine clearance
      (Clcr), resulted in a similar ability to explain variance in prediction of Clcr.
      DESIGN: Included in the study were patients with stable renal function receiving
      total parenteral nutrition, who underwent a 24-hour urine collection and had an
      SCr < 85 mumol/L. Clcr was calculated (CalcClcr) using the Cockcroft-Gault
      method, and actual SCr, and an SCr value set at 85 mumol/L (AdjCalcClcr).
      Calculated values were compared with 24-hour measured Clcr (MeasClcr). SETTING:
      Inpatient, acute-care hospital. PATIENTS: 33 patients having 33 urine-collection
      periods. All patients were receiving total parenteral nutrition as their only
      form of nutritional supplement. Patients who had liver disease, trauma, or burns,
      or who were receiving certain pharmacologic agents, were excluded from the study.
      MAIN OUTCOME MEASURES: MeasClcr based on the 24-hour urine collection, CalcClcr
      computed using the actual measured SCr, and SCr adjusted to 85 mumol/L. RESULTS:
      A higher proportion of the variance of measured versus calculated Clcr was
      explained by the using the actual measured SCr value (r2 = 0.68) than SCr
      adjusted to 85 mumol/L (r2 = 0.32). When analyzed by gender, adjusting the SCr to
      85 mumol/L was somewhat better at explaining the variance of measured versus
      calculated Clcr, but still explained less than 50 percent of the variance.
      However, the use of the actual SCr explained more of the variance of measured
      versus calculated Clcr than the use of the SCr value adjusted to 85 mumol/L.
      CONCLUSIONS: In patients with an SCr < 85 mumol/L, the actual measured SCr should
      be used when calculating Clcr (regardless of the patient's gender), by the
      Cockcroft-Gault method.

PMID- 8305772
TI  - Prescribing attitudes of different physician groups regarding fluoxetine.
AB  - OBJECTIVE: To determine the attitudes and prescribing patterns of family medicine
      and psychiatric physicians regarding fluoxetine. DESIGN: A three-part
      questionnaire was distributed to the Departments of Family Medicine and
      Psychiatry. The survey included topics associated with fluoxetine use that have
      received broad professional attention, such as drug-induced suicidal and
      aggressive behavior. SETTING: The Family Practice Medical Group and the
      Department of Psychiatry at the University of Florida. PARTICIPANTS: Mailing
      lists from both above departments were used to distribute surveys to residents,
      fellows, and attending/faculty members of each department. Eighty-seven surveys
      were mailed. MAIN OUTCOME MEASURES: Survey questions were divided into three
      sections to help determine current attitudes of prescribing fluoxetine: eight
      short cases, 16 statements, and demographic data. RESULTS: The return rate was 69
      percent following a mailing and a hand-delivered copy. Responses were
      dichotomized to agree or disagree and were analyzed by Fisher's exact test.
      Psychiatrists were much more likely than family practitioners to prescribe
      fluoxetine for obsessive-compulsive disorder (OCD), and more likely to prescribe
      for a patient with a history of substance abuse or seizure disorder.
      Psychiatrists were more aware of safety issues; however, drug-interaction
      knowledge was weak in both groups. CONCLUSIONS: Family practitioners, being the
      most predominant of medical specialists, appeared equally comfortable with
      prescribing fluoxetine in most circumstances compared with psychiatrists.
      However, there is a need for pharmacists to provide up-to-date drug information
      on fluoxetine to all healthcare professionals.

PMID- 8305773
TI  - Phenytoin concentration elevation subsequent to ranitidine administration.
AB  - OBJECTIVE: To report elevated phenytoin (PHT) plasma concentrations in a patient
      receiving ranitidine. CASE SUMMARY: A patient treated with PHT and ranitidine
      experienced elevated PHT plasma concentrations that persisted several days after
      PHT was discontinued. The PHT plasma concentration declined rapidly after
      withdrawal of ranitidine. DISCUSSION: This is an unusual case report of elevated
      PHT plasma concentrations associated with concurrent ranitidine use. Ranitidine
      has been reported to interfere with the hepatic metabolism of other drugs. The
      proposed mechanism of this interaction is similar to that of other histamine 2
      receptor antagonists--by binding to cytochrome P-450 hepatic mixed-function
      oxidase. We postulate that a small subset of patients may be susceptible to this
      effect of ranitidine. CONCLUSIONS: This case was complicated by several variables
      that may have affected the changes observed in total PHT concentrations. However,
      an interaction between ranitidine and PHT should be considered, especially in a
      subpopulation of patients that are more susceptible to this effect. Patients
      using ranitidine and phenytoin concurrently should be routinely monitored.

PMID- 8305774
TI  - Fluosol: therapeutic failure in severe anemia.
AB  - OBJECTIVE: To report the use of Fluosol in the management of a severe anemia and
      to review the literature regarding the use of Fluosol. CASE REPORT: A 40-year-old
      woman, at 40.5 weeks gestation, was admitted for induction of labor. Her hospital
      course was complicated by a postpartum hemorrhage and severe anemia. Because the
      patient was a Jehovah's Witness, she received non-blood products including
      hetastarch, iron dextran, and erythropoietin, and a total of 33 mL/kg of Fluosol,
      but she did not survive. DISCUSSION: Fluosol is an oxygen-carrying,
      perfluorochemical blood substitute. It was administered to our patient, who
      presented with the lowest hemoglobin (Hb) (11 g/L) and hematocrit (0.31 fraction
      of 1.00) of all reported cases. Almost all patients with an Hb < 20 g/L do not
      survive. CONCLUSIONS: Although the use of Fluosol as a blood substitute appears
      theoretically promising, its use in the management of severe anemia cannot be
      recommended.

PMID- 8305775
TI  - Fluvoxamine-associated manic behavior: a case series.
AB  - OBJECTIVE: To report cases of manic-like behavior induced by fluvoxamine, a
      selective serotonin-reuptake inhibitor; to review pertinent literature; and to
      encourage replication of our findings in larger patient samples. DESIGN:
      Description of a case series of fluvoxamine-induced, manic-like behavior.
      PATIENTS: Eight patients with depression or obsessive features who developed
      manic-like behavior after initiation of fluvoxamine therapy. RESULTS: Manic
      symptomatology resolved in all eight patients following dosage reduction or
      withdrawal of fluvoxamine. Four patients still are maintained on low-dose
      fluvoxamine without recurrent manic symptoms. CONCLUSIONS: Our case series
      suggests that fluvoxamine may have the ability to induce or unmask manic behavior
      in depressed patients. Clinicians are alerted to monitor for this "switching"
      effect, especially in patients previously or currently treated with neuroleptics
      or lithium, and in those patients exhibiting characteristics of obsessive
      compulsive disorder.

PMID- 8305776
TI  - Vesicular eruptions following acyclovir administration.
AB  - OBJECTIVE: To report the occurrence of vesicular lesions on the skin of a child
      receiving intravenous acyclovir therapy. CASE SUMMARY: A 12-year-old boy with
      presumed herpes simplex encephalitis developed cutaneous vesicular lesions
      following intravenous acyclovir administration. The lesions were initially
      thought to be herpetic. Further evaluation of the vesicle fluid and the temporal
      relationship of the development of the lesions with acyclovir administration led
      to the conclusion that the reaction was drug induced. DISCUSSION: Although
      inflammation and phlebitis are fairly common after acyclovir infusion, the
      development of vesicular lesions appears to be rare. Only two cases, both in
      adults, have been published in the medical literature. Although several theories
      have been proposed, including hypersensitivity, local drug toxicity, and tissue
      damage associated with extravasation, the mechanism of this reaction remains
      unclear. CONCLUSIONS: Vesicular eruption is a rare adverse reaction in patients
      receiving acyclovir. Careful evaluation is necessary to differentiate this
      reaction from herpetic lesions.

PMID- 8305777
TI  - Treatment of cryptosporidial diarrhea in an AIDS patient with paromomycin.
AB  - OBJECTIVE: To report a case of diarrhea caused by Cryptosporidium in an AIDS
      patients which was successfully treated with paromomycin. CASE SUMMARY: An AIDS
      patient with a 12-month history of cryptosporidial diarrhea unresponsive to other
      treatment measures was treated with paromomycin 500 mg q6h for 14 days. Before
      initiating therapy, the patient was experiencing, on average, 20 bowel movements
      per day and had lost more than 25 kg. After therapy was initiated, the number of
      bowel movements dropped to 1-2 per day and the patient began to gain weight. The
      diarrhea recurred when therapy was discontinued. After retreatment for 14 days
      with paromomycin 500 mg q6h, the diarrhea stopped. The patient has not had a
      recurrence of Cryptosporidium diarrhea, stool cultures remain negative for
      Cryptosporidium oocysts, and the patient has regained most of the weight.
      DISCUSSION: Literature concerning the use of paromomycin for the treatment of
      cryptosporidiosis is discussed. A treatment algorithm for the management of
      cryptosporidiosis in AIDS patients is presented. CONCLUSIONS: We believe that we
      have presented a clear example of a case in which paromomycin was effective in
      treating and eradicating intestinal cryptosporidiosis in an AIDS patient.
      Paromomycin is the most effective agent available to date for the treatment of
      this devastating complication of AIDS.

PMID- 8305778
TI  - Amiodarone-clonazepam interaction.
AB  - OBJECTIVE: To describe a potential drug interaction between amiodarone and
      clonazepam. CASE SUMMARY: A 78-year-old man with a history of congestive heart
      failure and coronary artery disease began taking amiodarone to suppress sustained
      ventricular tachycardia. Following the development of restless leg syndrome,
      therapy with clonazepam 0.5 mg qhs was initiated. Subsequently, the patient
      demonstrated signs and symptoms of benzodiazepine toxicity, which cleared
      following the discontinuation of clonazepam. DISCUSSION: Amiodarone is a Class
      III antiarrhythmic with an adverse-effect profile involving many different organ
      systems. It also has been shown to inhibit the metabolism of drugs cleared by
      oxidative microsomal enzymes. Clonazepam undergoes extensive hepatic metabolism,
      primarily by reduction and acetylation, and is therefore susceptible to altered
      disposition during concomitant administration of agents that inhibit hepatic
      microsomal enzymes. Hypothyroidism, occurring in up to 11 percent of patients
      treated with amiodarone, can also alter drug metabolism and sensitize the central
      nervous system, thus increasing the potential for toxicity. It is likely that a
      combination of these factors was responsible for the symptoms described in this
      patient. CONCLUSIONS: The complex pharmacologic profile of amiodarone and its
      effects on multiple organ systems necessitates close patient monitoring during
      concurrent administration of medications such as clonazepam, which are cleared by
      oxidative metabolism.

PMID- 8305779
TI  - Acute pancreatitis associated with the use of lisinopril.
AB  - OBJECTIVE: To report a case of acute pancreatitis associated with lisinopril use.
      CASE SUMMARY: A 67-year-old man with no past history of pancreatitis or its
      associated risk factors developed acute pancreatitis after taking lisinopril for
      two years. To date, the use of angiotensin-converting enzyme (ACE) inhibitors and
      development of pancreatitis has been described in the literature with captopril,
      enalapril maleate, and one case temporally related to lisinopril use.
      CONCLUSIONS: The use of ACE inhibitors as first-line agents in controlling
      hypertension and congestive heart failure has increased. In addition to
      monitoring for efficacy and commonly reported adverse effects, clinicians need to
      be aware that acute pancreatitis may occur with all ACE inhibitors.

PMID- 8305780
TI  - Ciprofloxacin-induced toxic epidermal necrolysis.
AB  - OBJECTIVE: To report a case of probable ciprofloxacin-induced toxic epidermal
      necrolysis (TEN) in an adult with systemic lupus erythematosus (SLE). CASE
      SUMMARY: A 31-year-old woman with SLE developed a pruritic rash following her
      first dose of oral ciprofloxacin. She continued taking ciprofloxacin, and the
      rash progressively worsened, becoming painful and covering her entire body. She
      discontinued the ciprofloxacin six days later and presented to the hospital,
      where two days later, her rash began to desquamate with epidermal erosions and a
      positive Nikolsky's sign. Skin biopsy was positive for TEN. She then was
      transferred to a burn-treatment unit because of the severity of the skin
      involvement. The patient recovered following prolonged hospitalization and
      rehabilitation. CONCLUSIONS: Although TEN occurs rarely with ciprofloxacin,
      extensive postmarketing surveillance needs to be performed to determine other
      risk factors for its development and to establish the incidence of TEN and other
      severe cutaneous reactions caused by ciprofloxacin or the other fluoroquinolones.

PMID- 8305781
TI  - Osteoporosis as a result of inhaled steroids.

PMID- 8305782
TI  - Use of ursodeoxycholic acid in primary biliary cirrhosis.

PMID- 8305783
TI  - Evening primrose oil in rheumatoid arthritis.

PMID- 8305784
TI  - Atovaquone: a review.
AB  - OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical
      efficacy, and safety of atovaquone. DATA IDENTIFICATION: An English-language
      literature search using MEDLINE (1984-1993), programs and abstracts of the 30th,
      31st, and 32nd Interscience Conferences on Antimicrobial Agents and Chemotherapy,
      program and abstracts of the VIII International Conference on AIDS, and
      unpublished information from Burroughs Wellcome, the manufacturer of atovaquone.
      STUDY SELECTION: All available pharmacokinetic and clinical trials were reviewed.
      DATA EXTRACTION: Study quality was assessed by a critical appraisal of study
      design and methods. Pharmacokinetic studies were evaluated for sampling, methods
      used to determine pharmacokinetic properties, and the presence of concentration
      response and concentration-toxicity relationships. Clinical trials were assessed
      primarily for comparative efficacy and toxicity. RESULTS: Atovaquone is a novel
      hydroxynaphthoquinone with potent activity against Pneumocystis carinii and
      Toxoplasma gondii. Its pharmacokinetic properties are characterized by relatively
      poor bioavailability, excretion almost exclusively through the feces, lack of
      hepatic metabolism and urinary excretion, low steady-state plasma concentrations,
      high protein binding, and a long elimination half-life (50-70 h). Results from
      comparative clinical trials in AIDS patients with mild-to-moderate P. carinii
      pneumonia (PCP) reveal similar overall treatment success rates for atovaquone,
      trimethoprim/sulfamethoxazole (TMP/SMX), and pentamidine. Treatment failure
      because of lack of therapeutic response was significantly greater in patients who
      received atovaquone compared with those treated with TMP/SMX (p = 0.002). More
      atovaquone-patients experienced treatment failure compared with their pentamidine
      treated counterparts, although statistical significance was not achieved.
      Treatment failure secondary to drug toxicity was significantly higher in the
      TMP/SMX- and pentamidine-treated patients (p < or = 0.01). Atovaquone has not
      been studied for PCP prophylaxis. Limited data exist on the use of atovaquone for
      toxoplasmic encephalitis (TE); however, results from an open trial reveal that
      the drug may be useful in treating this disorder. To date, atovaquone has been
      well tolerated by most patients administered the drug. The most common adverse
      effects include maculopapular rash, gastrointestinal disturbances, and fever.
      Atovaquone is considerably more costly than other oral agents used to treat PCP.
      CONCLUSIONS: Atovaquone appears to be better tolerated but less effective than
      TMP/SMX and pentamidine in the treatment of mild-to-moderate PCP. There is not
      enough information available on the use of atovaquone for PCP prophylaxis or the
      treatment of TE to definitively describe its efficacy. Comparative clinical
      trials are needed to assess its role in this clinical setting.

PMID- 8305785
TI  - New therapeutic agents in the management of hypertension: angiotensin II-receptor
      antagonists and renin inhibitors.
AB  - OBJECTIVE: To review the chemistry, pharmacokinetics, and clinical trials of two
      new classes of antihypertensive drugs, angiotensin II-receptor antagonists and
      renin inhibitors. DATA SOURCES: Primary literature on angiotensin II-receptor
      antagonists and renin inhibitors was identified through a comprehensive medical
      literature search from 1961 through 1993. This search included journal articles,
      abstracts, and reports of both animal and human research published in the English
      language. Indexing terms included renin-angiotensin aldosterone system, renin
      inhibitors, angiotensin II antagonists, DuP 753, losartan, MK954, A-64662, and Ro
      42-5892. STUDY SELECTIONS: Emphasis was placed on clinical and pharmacokinetic
      studies in humans for drugs that are currently in Phase I-III research protocols
      in the US. DATA EXTRACTION: All available data from human studies were reviewed.
      DATA SYNTHESIS: Angiotensin II-receptor antagonists and renin inhibitors may be
      effective antihypertensives with few adverse effects noted in the small studies
      completed. Their potential advantage over angiotensin-converting enzyme (ACE)
      inhibitors includes a possible smaller adverse effect profile. In the past, the
      clinical utility of angiotensin II-receptor antagonists and renin inhibitors has
      been limited because of poor oral bioavailability, although newer agents are more
      readily bioavailable. CONCLUSIONS: Angiotensin II-receptor antagonists and renin
      inhibitors may be the next new classes of antihypertensives marketed. However,
      definitive conclusions about their roles in the management of hypertension are
      not possible until larger clinical trials assessing their efficacy and safety and
      comparing them with ACE inhibitors are completed.

PMID- 8305786
TI  - So much writing, so little science: a review of 37 years of literature on edetate
      sodium chelation therapy.
AB  - OBJECTIVE: To determine the safety and efficacy of edetate sodium
      (ethylenediamine tetraacetic acid; EDTA) chelation therapy for atherosclerosis.
      METHODS: Literature search using MEDLINE, encompassing 1966 through May 1993.
      Further references were obtained from articles and books, and from citations
      obtained from the American Academy of Medical Preventics. RESULTS: 16 case
      reports or case series, 2 longitudinal studies, and 3 clinical trials were
      reviewed, along with testimonials cited in 19 books. CONCLUSIONS: Little valid
      scientific evidence is available. Although the postulated mechanisms of action
      for EDTA are biologically plausible and EDTA appears to be safe, it has not been
      proven effective. Indeed, the best evidence shows it to be ineffective.
      Therefore, EDTA chelation therapy should not be used in clinical practice to
      treat atherosclerosis.

PMID- 8305787
TI  - Pharmacotherapy of disseminated histoplasmosis in patients with AIDS.
AB  - OBJECTIVE: To review the pharmacotherapy of disseminated histoplasmosis (DH) in
      patients with AIDS. The article provides an overview of the pathophysiology,
      epidemiology, clinical presentation and diagnosis of this disease. Clinical
      trials reporting intervention with antifungal therapy are reviewed, with an
      emphasis on efficacy and toxicity of these agents. DATA SOURCES: A MEDLINE search
      from 1976 to the present was performed to identify pertinent biomedical
      literature, including reviews. STUDY SELECTION: All available reviews and
      clinical trials in AIDS patients were evaluated, as were all available case
      series and interventional clinical trials. DATA SYNTHESIS: DH in patients with
      HIV infection is an AIDS-defining opportunistic infection caused by Histoplasma
      capsulatum. It is most frequently observed in HIV-infected patients living in or
      traveling to endemic regions. The clinical presentation most often includes fever
      and weight loss, but may be complicated by comorbid illness such as other
      opportunistic infections. Diagnosis is best established by histologic examination
      of peripheral blood smear or bone marrow aspirate, or isolation of the organism
      in cultures of blood, bone marrow, and respiratory secretions. Serologic
      examinations may provide supportive diagnostic information. Detection of
      histoplasma polysaccharide antigen (HPA) in serum or urine may prove to be a
      promising approach for the rapid diagnosis and therapeutic monitoring of DH in
      AIDS patients. In contrast to immunocompetent hosts, high relapse rates are
      reported after therapy in AIDS patients. Therefore, initial (induction) therapy
      is routinely followed by long-term (maintenance) therapy to prevent relapse.
      Issues regarding the selection, dosage, and duration of therapy, as well as
      prophylaxis of patients at highest risk, still need to be addressed by controlled
      clinical trials. CONCLUSIONS: Amphotericin B is presently the drug of choice for
      induction therapy. Maintenance therapy with either amphotericin B or an oral
      azole antifungal agent active against H. capsulatum is necessary to prevent
      relapse. Itraconazole, a triazole antifungal agent, may provide effective
      alternative therapy for both induction and maintenance treatment of DH.

PMID- 8305788
TI  - Newer insights into cisplatin nephrotoxicity.
AB  - OBJECTIVE: To review recent advances in the understanding of the mechanisms of
      cisplatin nephrotoxicity. Factors affecting this toxicity and agents that may
      protect against it are discussed. DATA SOURCES: A MEDLINE search was used to
      identify pertinent literature including reviews. A manual search of
      bibliographies was performed to include all articles on the subject. STUDY
      SELECTION: All available data relating to the mechanisms, modifying factors, and
      management of cisplatin nephrotoxicity were assessed. DATA EXTRACTION: As limited
      human data are available, all animal studies were included. Articles with
      hypotheses or suggestions not backed by scientific data were excluded from
      review. DATA SYNTHESIS: Cisplatin is one of the most effective agents available
      for treating a variety of solid tumors. Nephrotoxicity is the dose-limiting
      factor for the use of this drug. Mechanisms for renal toxicity range from
      definitive histologic changes found in the proximal convoluted tubules to
      physiologic and biochemical alterations involving a decrease in mitochondrial
      respiratory function, enzymatic activity in the respiratory chain and glutathione
      peroxidase, and effects on cellular calcium homeostasis. Important factors
      related to nephrotoxicity include age, renal irradiation, and concurrent alcohol
      intake. Agents that appear promising in attenuating the nephrotoxic effects of
      cisplatin include loading with NaCl solution and/or mannitol, sodium thiosulfate,
      WR 2721, glutathione, probenecid, and many other compounds under active
      investigation. CONCLUSIONS: Cisplatin is a nephrotoxic drug; however, agents that
      may make cisplatin therapy more safe and rewarding will be available in the near
      future.

PMID- 8305789
TI  - Therapeutic monitoring and pharmacist intervention in a Hansen's disease clinic.
AB  - OBJECTIVE: To describe the role of the clinical pharmacist in a Hansen's disease
      (HD, leprosy) clinic and to describe the development, validation, and operation
      of a dapsone compliance monitoring program. RATIONALE: HD remains a major,
      worldwide healthcare problem. Dapsone is the drug of choice for treatment of HD;
      however, high rates of noncompliance with this agent have been reported by many
      treatment centers. The assessment of compliance in HD patients is important to
      help distinguish between treatment failure secondary to noncompliance or to the
      development of resistance. SETTING: In the US, the Chicago Regional Hansen's
      Disease Center at the University of Illinois at Chicago is one of ten centers
      that provide comprehensive care to patients diagnosed with this condition. This
      article reviews the clinical pharmacy services and dapsone compliance program in
      the clinic encompassing the years 1983-93. RESULTS: The clinical pharmacist
      provides a variety of clinical services in the clinic as well as coordinating the
      clinical research program. A pharmacist-generated dapsone compliance program led
      to improvement in compliance rates and clinical outcome. This improvement in
      compliance has been sustained over an extended period of time. CONCLUSIONS: The
      clinical pharmacy services performed in the HD clinic provide a model for
      pharmacy involvement in other chronic disease states. The dapsone compliance
      program has been successful in improving patient care and obtaining reimbursement
      for clinical pharmacy services.

PMID- 8305790
TI  - Risk for adverse events among patients receiving intravenous histamine2-receptor
      antagonists.
AB  - OBJECTIVE: To identify risk factors for adverse drug reactions (ADRs) in patients
      receiving intravenous histamine2-receptor antagonists (H2-RAs). DESIGN: The study
      hypothesis was evaluated by performing a logistic regression procedure with a
      backward elimination of the explanatory variables associated with ADRs. MAIN
      OUTCOME MEASURES: ADRs temporally associated with the use of intravenous H2-RAs
      served as the dependent variable. Background information about the patients and
      drug use evaluation criteria in three general areas were entered into the
      regression analysis. SETTING: Hospitals were selected from the southeastern US,
      based on their willingness to participate and their characteristics.
      Participating hospitals exhibited a variety of sizes and ownership arrangements.
      PATIENTS: 1200 adult patients who were receiving intravenous H2-RAs. RESULTS:
      Seven percent of patients experienced a presumed ADR (PADR) to intravenous H2
      RAs. The only risk factor for ranitidine was for patients who did not have their
      dosage corrected for renal function ("overdose"); these patients were twice as
      likely to experience a PADR compared with patients who received the correct
      dosage as determined by their renal function. Two risk factors for cimetidine
      were identified: (1) patients taking cimetidine with another medication known to
      cause a drug interaction; and (2) patient age. No risk factors were identified
      for famotidine. CONCLUSIONS: The two risk factors for ADRs identified in this
      study are preventable. Healthcare providers should strive to prevent ADRs by
      adjusting patients' dosages based on their renal function and by monitoring
      patients receiving cimetidine with another medication known to interact with
      cimetidine.

PMID- 8305791
TI  - Aluminum and intravenous drugs in the neonate.

PMID- 8305792
TI  - Acute iritis and transient renal impairment following thrombolytic therapy for
      acute myocardial infarction.

PMID- 8305793
TI  - Atypicality of clozapine.

PMID- 8305794
TI  - Drug-induced lupus-like reaction and captopril.

PMID- 8305795
TI  - Comment: assessing the quality of pharmaceutical care.

PMID- 8305796
TI  - Comment: sedative efficacy of midazolam in a pediatric ICU.

PMID- 8305797
TI  - Comment: verapamil interaction with ceftriaxone and clindamycin.

PMID- 8305798
TI  - Comment: pitfalls in reporting drug interactions.

PMID- 8305799
TI  - Comment: paroxetine-associated hyponatremia.

PMID- 8305800
TI  - Encapsulated anaerobic bacteria in clinical infections.

PMID- 8305801
TI  - Changing strategies in aminoglycoside dosing; the result of research on
      antimicrobial pharmacodynamics.

PMID- 8305802
TI  - Ultrastructure of mycobacterial surfaces by freeze-substitution.
AB  - The global status of tuberculosis has recently received much public attention,
      particularly in some developed countries that are now reporting an increase in
      cases after several years of decline. A number of factors have contributed to the
      resurgence in tuberculosis and other mycobacterial infections, including
      homelessness, increased urban overcrowding among the poor, increased drug abuse
      and the AIDS epidemic. In addition, the intrinsic nature of mycobacterial
      impermeability to some antibiotics, and their ability to survive in host
      environments has been attributed to the unique chemistry and architecture of
      their walls. A better understanding of these surface-related properties could in
      turn lead to the design of more effective chemotherapeutic agents or potential
      vaccine candidates. Using freeze-substitution, we offer a revised perspective on
      mycobacterial wall design and discuss its significance.

PMID- 8305803
TI  - Contribution to some phenotypical characteristics of Vibrio cincinnatiensis.
      Studies in one strain of a diarrhoeic human patient and in two isolates from
      aborted bovine fetuses.
AB  - Until now, only a few strains of V. cincinnatiensis have been isolated. This
      study describes a further three isolates which originated in one case from a
      stool specimen of an immunocompromised elder patient suffering from enteritis and
      in two cases from the rennin stomachs of aborted bovine fetuses. These strains
      grew on TCBS, CIN, MacConkey and XLD plates. Their biochemical activities were
      dependent on NaCl concentration, in particular the formation of indole, lysine
      and ornithine decarboxylases, arginine dihydrolase, the reduction of nitrate and
      behaviour in the Voges-Proskauer test. Moreover, lysine decarboxylase and nitrate
      reductase were temperature-dependent. The knowledge of these hitherto unknown
      phenotypical characteristics may facilitate the diagnosis of the pathogen.

PMID- 8305804
TI  - Detection of H. pylori in saliva using a monoclonal antibody.
AB  - The presence of Helicobacter pylori in saliva specimens collected from infected
      children examined before and after specific therapy and from a non-infected
      pediatric population was detected by indirect immunofluorescence assay (IIF)
      using a specific monoclonal antibody. Among the 25 children with H. pylori
      negative antral biopsies, 4 had in their salivas bacterial cells similar to H.
      pylori, but a retrospectively performed serologic test showed a positive
      response. No false-positive reaction was observed among non-infected and
      seronegative children. The observation of bacterial cells with H. pylori
      morphology in saliva by IIF was consistent with the presence of this bacterium in
      antral biopsies. A person-to-person transmission of H. pylori by saliva thus
      appeared to be possible.

PMID- 8305805
TI  - Studies on binding of glycosaminoglycans to Streptococcus pyogenes by using 125I
      heparan sulphate as a probe.
AB  - Binding of 125I-heparan sulphate to the cell surface of Streptococcus pyogenes is
      mediated by proteins, that could be released from the streptococcal cell wall by
      using alkaline buffer. SDS-electrophoresis revealed two bands with molecular
      weights of 63 and 58 kDa. Binding of the 125I-labelled heparan sulphate probe to
      streptococci seems to be due to charge interactions, as the same probe was
      displaced by unlabelled heparan sulphate, other negatively charged molecules such
      as heparin, dextran sulphate, dermatan sulphate or by high ionic strength. The
      interaction was also strongly influenced by pH. The binding constant at pH 7.2
      was estimated to be 9.8 x 10(6) mol/l, suggesting a moderate affinity. The
      presence of collagen of different types enhanced binding of 125I-labelled heparan
      sulphate to streptococci, whereas fibronectin and vitronectin had an inhibitory
      effect. The cooperation between heparan sulphate and collagen could be important
      for the adhesion of streptococci to connective tissue.

PMID- 8305806
TI  - Antibiotic resistance of Shigella strains isolated in the Federal Republic of
      Germany 1989-1990.
AB  - A great many reports have been published about the multiresistance to strains of
      antibiotics in countries with a high incidence of shigellosis. In order to obtain
      better information about the situation in Germany, we tested 255 Shigella strains
      to 28 antibiotics during the 1989-1990 period. 153 (60%) of isolates originated
      from imported cases of infection (Middle and Far East, West and North Africa,
      Central America), whereas no history of infection in foreign countries was
      available for the remaining 102 strains. 207 (81.2%) of these strains were
      resistant to one or more antibiotics. They were divided into 6 phaenotypes
      according to their resistant pattern. The phaenotypes with the resistance
      patterns AMP, CMP, SM, SSS, TET as well as SM, SSS, TET in combination with SXT
      (38.6%) were most frequently isolated, followed by phaenotypes with the
      resistance pattern AMP, CMP, SM, SSS, or SM, SSS, combined with or without SXT
      (27.5%), and the phaenotypes AMP, CMP, SM, TET and CMP, SM, SSS, TET (15%). The
      incidence of resistance was significantly higher in strains from imported cases
      (93.5%) than in isolates from domestic infections (62.7%; p < 0.001). The
      similarity of the resistance patterns of strains acquired abroad and those
      acquired in Germany suggested that such strains might have been introduced from
      abroad. All strains were sensitive to the quinolones examined (ofloxacin and
      enoxacin) as well as to cephalosporines of the second and third generations.

PMID- 8305807
TI  - Induction of the release of prostaglandin E2 from polymorphonuclear neutrophil
      granulocytes by Bacteroides fragilis: its possible role in the pathogenesis of
      mixed infections.
AB  - The presence of anaerobic bacteria, especially of Bacteroides (B.) fragilis, in
      abdominal abscesses, infected decubitus ulcera, and the infected foot of diabetic
      patients is well documented. The importance, however, of these microorganisms in
      the pathogenesis of deep tissue infections has still to be evaluated. Therefore,
      the aim of this study was to evaluate the potency of B. fragilis as compared to
      aerobic bacteria widely known for causing inflammation, in inducing the release
      of prostaglandin E2 from polymorphonuclear granulocytes. Prostaglandin E2 is a
      potent vasodilator and contributes to edema and erythema, which are part of the
      inflammatory response. Furthermore, the cAMP-content of the neutrophils was
      determined after stimulation of the cells with the various bacteria. Of the
      bacterial species tested, B. fragilis proved to be one of the most potent
      triggers for prostaglandin E2 release from neutrophils indicating a possible
      major role of this microorganism in the pathogenesis of mixed infections.

PMID- 8305808
TI  - A case of laboratory acquired infection with Escherichia coli O157:H7.
AB  - A case of laboratory-acquired infection with Escherichia coli O157:H7 is
      presented. Evidence of the identity of the infecting strain was provided by toxin
      type and plasmid profiles. Because no obvious technical errors in laboratory
      practices could be demonstrated we conclude that the infecting dose for E. coli
      O157:H7 may be small. The clinical course was uncomplicated; during
      reconvalescence, the patient's serum recognized a unique 87 kDa band on
      immunoblots of the infecting strain.

PMID- 8305809
TI  - Comparison of serological tests for the detection of antibodies against Chlamydia
      trachomatis and Chlamydia pneumoniae in rheumatological patients.
AB  - In cases of reactive arthritis, a suspected Chlamydia trachomatis infection is
      often detected by serological methods. However, mostly tests with genus-specific
      antigens are used, neglecting the fact that antibodies against Chlamydia
      pneumoniae are highly prevalent in the adult population. Therefore we tested sera
      of 129 patients with various rheumatological disorders and of 18 healthy persons
      in parallel with a genus-specific test (IPAZYME) and with the species-specific
      microimmunofluorescence test for C. trachomatis and C. pneumoniae antibodies. The
      data showed that 55% of the 64 IPA-positive results were caused by antibodies
      (IgG) against Chlamydia pneumoniae, only 6% by anti-Chlamydia trachomatis IgG and
      20% by both specificities. For IgA antibodies, the percentages were 44%, 12.5%
      and 12.5% respectively. In 12 IPA-positive cases, the MIF showed no reaction. 58%
      of all 147 sera tested with MIF had IgG antibodies against C. pneumoniae, 5% had
      anti-C. trachomatis IgG and 8% IgG against both species. The percentages for IgA
      were 29%, 2% and 2%, respectively. IgM positivity in MIF disappeared after
      absorption with rheumatoid factor absorbent. No significant differences were
      found between the various groups of patients. The data suggest that due to the
      high prevalence of anti-C. pneumoniae antibody, genus-species tests cannot be
      used as screening tests for the serological diagnosis of C. trachomatis
      infections.

PMID- 8305810
TI  - Simian agent 8 (SA8): morphogenesis and ultrastructure.
AB  - Electron microscopic studies on the morphogenesis of SA8 in primary rabbit brain
      cell cultures revealed that in early stages of infection, envelopment of
      nucleocapsids commonly occurred at the inner nuclear membrane. From the
      perinuclear space, enveloped virus particles moved into the cisternae of the
      endoplasmic reticulum (ER) in which they were transported, through the cytoplasm,
      to the plasma membrane. Alternatively, de-envelopment at the outer nuclear
      membrane and egress of naked capsids into the cytoplasm were frequently observed.
      Non-enveloped cytoplasmic capsids were also a consistent feature of cells in late
      stages of infection, when nuclear membranes became ruptured. In these cases, the
      envelopment of naked capsids took place by budding either into the cisternae of
      ER or into cytoplasmic vesicles and vacuoles, in which transport to and
      exocytosis at the cell membrane occurred. Budding at the cell membrane was rarely
      found. Capsids of enveloped particles were asymmetrically surrounded by an
      electron-dense layer which may be identical to the tegument. Because only
      enveloped cytoplasmic and free virions were tegumented we suggested that the
      tegumentation must occur during the envelopment (budding) into cytoplasmic
      vesicles and at the plasma membrane.

PMID- 8305811
TI  - Identification of staphylococci from bovine milk in Argentina.
AB  - Two hundred and thirty three strains of staphylococci isolated from bovine milk
      from 17 dairies in Argentina were classified into 16 species. Most of the strains
      (78%) belonged to 4 species; S. aureus, S. haemolyticus, S. hominis, and S.
      warneri (38.5, 20.5, 9.4 and 9.0%, respectively). The remaining 12 species
      appeared with low frequencies. Twenty-one of the strains were isolated from
      mammary quarters with signs of clinical mastitis. The majority of the milk
      samples infected with S. aureus or S. haemolyticus showed very high somatic cell
      counts.

PMID- 8305812
TI  - The distribution of Acinetobacter species in clinical culture materials.
AB  - A total of 584 Acinetobacter strains were isolated from 420 patients from 12
      different hospitals over a period of twelve months. Identification of strains at
      the species level was done according to the new taxonomy proposed by Bouvet and
      Grimont. A. baumannii strains were isolated most frequently (n = 426; 72.9%),
      followed by A. species 3 (n = 55), A. johnsonii (n = 29), and A. lwoffii (n =
      21). Most isolates were recovered from respiratory tract specimens (n = 251;
      42.9%), blood cultures (n = 116; 19.9%), wound swabs (n = 90; 15.4%), catheter
      tips (n = 75; 12.8%), and urinary tract specimens (n = 20; 3.4%). Strains
      belonging to species other than A. baumannii were isolated more frequently (n =
      158; 27.1%) than previously reported, mainly from blood cultures, respiratory
      tract specimens, and central venous catheters.

PMID- 8305813
TI  - Comparative characterization of Acinetobacter strains isolated from different
      foods and clinical sources.
AB  - Eighty-three Acinetobacter strains from clinical sources, and 170 from various
      foods (including fresh and spoiled meat and fish, vegetables, raw milk and
      cheese) were identified according to recently improved taxonomy, using a computer
      assisted probabilistic method based on phenotyping tests. Apart from some
      atypical characters, most of the strains (94%) were identified to belong to the
      genospecies or groups of genospecies described in the literature. Among our
      strains from hospitals, the A. calcoaceticus- A. baumannii complex predominated,
      whereas the strains isolated from food were predominated by genospecies 7 (A.
      johnsonii), followed by genospecies 8/9 (A. lwoffii). The isolates from clinical
      environments showed a major incidence of antibiotic resistance, haemolytic
      strains and strains producing polysaccharidic material.

PMID- 8305814
TI  - Goodpasture's syndrome in aging. An experimental study on the rat. I.
AB  - The following hypothesis is proposed: Experimental lung disease in old rats is
      different from this disease in adult rats. In order to demonstrate this, we
      performed a morphometrical evaluation of the pulmonary state of two groups of
      rats at different ages and to which Goodpasture's syndrome had been induced. 115
      Wistar rats were used. They were divided into four different groups as follows:
      1) Healthy adult rats which had not been subjected to treatment; 2) diseased
      adult rats to which antipulmonary serum had been administered; 3) healthy old
      rats; and 4) diseased old rats. With the help of a computerized system, the
      length of the alveolar chord, the thickness of the alveolar wall and the surface
      of the bronchial-associated lymphoid tissue in each group was calculated. We also
      counted the number of alveolar macrophages (AM) with haemosiderin, the percentage
      of goblet bronchial cells and that of AM, lymphocytes and polymorphonuclear
      leukocytes of the broncho-alveolar lavage (BAL). The following results were
      obtained. When related to the diseased adult rats, the diseased old rats showed
      an increase in the alveolar chord and a decrease in the thickness of the alveolar
      wall, as well as in the number of AM with haemosiderin, goblet cells and BAL
      lymphocytes. These results support the proposed hypotheses, since the diseased
      adult animals showed signs of alveolar inflammation with interstitial edema,
      while in the diseased old animals these results are compatible with emphysema.

PMID- 8305815
TI  - Goodpasture's syndrome in aging. An experimental study on the rat. II.
AB  - The following hypothesis is suggested: if a lung disease is induced in an adult
      rat, then its lung, in the senile age, will be different from what is considered
      to be a normal senile lung. In order to demonstrate this, the pulmonary state of
      two groups of old rats, one of which had suffered from Goodpasture's syndrome in
      the adult age has been assessed morphometrically. Fifty-three Wistar rats were
      used. They were divided into two groups: 1) healthy old rats; and 2) diseased old
      rats. Antipulmonary serum was administered to the latter and they were sacrificed
      a year later. Making use of a computing system, we calculated the following data
      for each group: the alveolar chord length, the alveolar wall thickness and the
      surface of the bronchial-associated lymphoid tissue (BALT). The alveolar
      macrophages (AM) with haemosiderin which were found in the lung tissue were also
      counted and the percentage of goblet bronchial cells and that of bronchoalveolar
      lavage (BAL) cells was also assessed. From the results, the following points
      should be emphasized: in diseased old rats, an increase in the alveolar chord, a
      decrease in lymphocytes with an increase in the AM of the BAL, and a decrease in
      goblet cells and AM with haemosiderin occur, all of which are significant when
      these rats are compared to healthy old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305816
TI  - "Neuroendocrine" differentiation in hepatocellular carcinomas (HCCs):
      immunohistochemical reactivity is related to distinct tumor cell types, but not
      to tumor grade.
AB  - We have analyzed neuroendocrine differentiation (ND) in hepatocellular carcinomas
      (HCCs) of fifty patients. It turned out that ND is frequent in HCCs, and that it
      is not restricted to fibrolamellar hepatocellular carcinoma (FL-HCC).
      Multiexpression is seen in a quarter of the cases, and marker coexpression may
      occur within the same tumor cell. ND predominates in trabecular and mixed HCCs,
      but does not appear to be related to grade. Most positive cases showed a
      hepatocyte-like cell morphology, frequently associated with bile formation. It
      thus appears that the HCC cell type most likely to show ND is a hepatocyte-like
      one, i.e. differentiated cell, frequently polarized and producing bile, rather
      than a small and poorly-differentiated cell. Possible pathogenic mechanisms
      leading to ND in HCCs are briefly discussed.

PMID- 8305817
TI  - Effects of chronic low-level copper exposure on ultrastructure of the olfactory
      system in rainbow trout (Oncorhynchus mykiss).
AB  - This study investigated the effects of a chronic exposure to a low level of
      copper on cell populations of the olfactory system in yearling rainbow trout.
      Fish were sacrificed after 15, 30 and 60 days of copper exposure. Transmission
      electron microscopy was used to describe the sequence of subcellular changes
      occurring in three tissues, the sensory epithelium, the olfactory nerve and the
      olfactory bulb. Data show that a 15-day exposure to 20 micrograms/l of copper
      causes specific degeneration of all mature receptor cells as well as numerous
      immature neurons. Moreover, degenerating receptor cells exhibited morphological
      features of a cell death by apoptosis. After 30 days, and more specifically after
      60 days of exposure, numerous clusters of cells were observed in the basal region
      of the epithelium, suggesting a great mitotic activity in this area. In parallel,
      an increased number of maturing receptor cells and goblet cells were observed,
      but no fully mature neurons were noted even after 60 days of exposure. In both
      the olfactory nerve and the olfactory bulb, the number of degenerating axons and
      terminals, which was high at 15 days, decreased with time and some process of
      glomerular reinnervation was detected after 60 days. A reactive hypertrophy of
      supporting, ensheathing and astrocytic cells was also observed in exposed fish,
      which demonstrates that these cell types are actively involved in the process of
      tissue scarring. Even though some signs of neuronal regeneration were reported
      during the time-course of exposure, indicating some fish acclimation, results
      raise the question of the olfactory function during such environmental stress.

PMID- 8305818
TI  - Histochemical analysis of carbohydrate moieties and sugar-specific acceptors in
      the kidneys of the laboratory mouse and the golden spiny mouse (Acomys russatus).
AB  - The aims of this work were to histochemically compare the pattern of lectin
      binding and endolectin expression in different portions of nephrons of two rodent
      species producing either normal hyperosmotic urine (the laboratory mouse) or
      highly concentrated urine (Acomys russatus, the golden spiny mouse). A panel of
      biotinylated lectins and neoglycoproteins and the avidin-biotin-peroxidase
      complex technique were used on Bouin's fixed, paraffin-embedded sections. Various
      segments of the uriniferous tubule in both species showed differential affinity
      for labelled lectins and neoglycoproteins. Significant differences were also
      evident between comparable tubular segments in laboratory and golden spiny mouse
      kidneys. Whether the histochemical expression of sugar moieties of
      glycoconjugates as well as endolectins, thus both sides of presumed protein
      carbohydrate interactions, may be correlated to the various glycoproteins which
      would include constituents of the glycocalyx and domains of a variety of
      transport enzymes deserves further studies.

PMID- 8305819
TI  - Structural and ultrastructural study of the Meissner plexus in amphibians, Rana
      temporaria.
AB  - A study of the submucous, periglandular and intravillous plexus of the frog has
      been carried out with light microscopy and conventional electron microscopy. The
      existence of a true Meissner plexus, with light microscopy, as well as the
      existence of sensitive-like structures, with light and electron microscopy have
      been demonstrated in the frog.

PMID- 8305820
TI  - Immune complex-mediated glomerulopathy in Barbus graellsi infected with Myxobolus
      spp.
AB  - Membranous glomerulonephritis caused in Barbus graellsi by myxosporidian
      infections have been studied by electron microscopy and immunoelectron microscopy
      techniques. This study indicates that Myxosporidian infection produces a chronic
      severe aggression. Spores reach the spleen, the kidney and the liver, where they
      are trapped and phagocyted by Melano Macrophage Centres. Consequently, the
      commencement of a immunological response to myxosporidian is evident. Our results
      show the presence of immunodeposits in the basement membrane of the glomeruli,
      suggesting that they might initiate glomerulonephritis. The lesion was markedly
      similar to immune complex-mediated glomerulonephritis disease in higher
      vertebrates.

PMID- 8305821
TI  - Integrins in ageing cartilage tissue in vitro.
AB  - Matrix-cell interactions are of great importance for numerous cell functions
      whereby integrins play an essential role as transmitters of extracellular
      signals. In cultures of ageing cartilage tissue (organoid or high density
      cultures) cartilage cells occur on the surface of which thick fibrils of collagen
      type I are deposited. Since integrins, in their role as receptors, cause an
      interaction between matrix components and cell membrane, we tried to demonstrate
      immunomorphologically (light and electron microscopically) the corresponding
      integrin receptors for collagen type I (beta 1 alpha 1 and beta 1 alpha 2) on the
      surface of these ageing cartilage cells. Cultures of normal, i.e. young cartilage
      tissue exhibit only beta 1 alpha 3- and beta 1 alpha 5-receptors; labelling
      against the integrins beta 1 alpha 1 and beta 1 alpha 2 is not possible in this
      case. Our results show that after the occurrence of thick fibrils cartilage cells
      express new receptors (beta 1 alpha 1 and beta 1 alpha 2) on the cell membrane.
      Thus, in ageing or dedifferentiating cartilage tissue it is not only the
      synthesis programme of matrix components (e.g. instead of collagen type II >>
      collagen type I) which changes but also the integrins (instead of alpha 3/beta 1,
      alpha 5/beta 1 >> alpha 1/beta 1, alpha 2/beta 1) so that new collagen types can
      be bound. These findings may also serve for a better understanding and
      interpretation of cartilage changes in vivo during ageing and under pathological
      conditions.

PMID- 8305822
TI  - Cytological aspects of the human adrenal cortex development in the course of
      intra-uterine life.
AB  - Stereological studies were performed on 20 pairs of adrenal glands of human
      foetuses. The volume of particular adrenocortical zones, average cell volume and
      number of parenchymal cells were calculated. In 50 to 320 mm crown-rump length
      (C.-R.L.) foetuses (9-38 weeks of the intra-uterine life) an exponential increase
      in adrenal gland weight was found. If compared with the earlier period, the rate
      of increase was evidently higher beginning from the 20th week and depended mainly
      upon enlargement of the foetal zone, with less marked changes in the glomerulosa
      fasciculata zone. The zona glomerulosa (ZG) and the outer zona fasciculata (ZF)
      began to delineate by the 20th week of gestation. Zona reticularis was not
      observed in our material. From the beginning of development, fasciculata cell
      volume was markedly higher than that of ZG cells and lower than foetal zona (ZX)
      cells. Until the 20th week of intra-uterine life the volume of glomerulosa
      fasciculata zone (G-FZ) increased at a slow rate, while the rate of increase in
      volume of ZX was higher. After 20 weeks the rate of increase in volume of all
      adrenocortical zones was markedly higher (the same as that of the stroma). The
      volume of stroma in ZX markedly exceeded that in the remaining parts of the
      cortex. The average cell volume of ZG and ZF remained constant during the foetal
      period, while the average cell volume of ZX cells increased gradually from the
      9th to the 20th foetal week and afterwards remained unchanged. (ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8305823
TI  - Effects of neonatal treatment with MSG (monosodium glutamate) on hypothalamo
      pituitary-thyroid axis in adult male rats.
AB  - Neonatal administration of MSG leads to a syndrome of endocrine dysfunction
      characterised by reduced growth, obesity and hypogonadism. The aim of the present
      investigation was to gain information on the structure and function of the
      pituitary-thyroid axis in MSG-treated rats. Neonatal Wistar rats received an s.c.
      MSG (4 mg/g body weight) or hyperosmotic saline (controls) on days 2, 4, 6, 8 and
      10 of life. Histological and morphometrical studies were carried out on the
      thyroids of rats during the 4th month of life. Plasma TSH, T3, and T4 were
      measured by RIA kits. MSG-treated rats showed stunted growth, obesity and
      decreased pituitary weight. MSG administration resulted in increases in thyroid
      weight, absolute volumes of epithelium, colloid and stroma, and blood T3 level
      while T4 level remained unchanged. In enlarged thyroid gland, percentage
      fractions occupied by epithelium, colloid and stroma were similar to those
      observed in control rats. The results obtained suggest that the rat hypothalamic
      centres involved in regulation of the pituitary-thyroid axis are slightly
      affected by neonatal MSG treatment.

PMID- 8305824
TI  - Nerve fibres containing neuropeptide Y in the atrioventricular valves of Japanese
      monkey and rat; a light and electron microscopic study.
AB  - Dense distribution of varicose fibres containing neuropeptide Y-like
      immunoreactivity (NPY-LI) was found in the atrioventricular valves of the
      Japanese monkey, and moderately in the rat. The immunoelectron microscopy using
      immunogolds resulted in the localization of NPY-LI within the dense-cored
      vesicles which existed with the small clear vesicles in the unmyelinated axons
      near the endocardium. These NPY-LI-containing fibres may participate in
      regulation of vasomotor role or other functions of the atrioventricular valves.

PMID- 8305825
TI  - Insulitis and islet microvasculature in type 1 diabetes.
AB  - Type 1 diabetes is characterized by a mononuclear infiltration, commonly called
      "insulitis". The cells that constitute the insulitis are mainly monocytes that
      are recruited from extra-islet areas and arrive at the islet site via the
      vascular system. Infiltrating cells must then pass across the endothelia to gain
      access to the islet parenchyma. The anatomy and physiology of the islet
      microvasculature shows that islet B cells are firstly perfused and influence both
      endocrine non-B islet cells and peri-insular exocrine cells. The low dose
      streptozocin (LDS) treatment is able to induce, other than a monocyte/macrophage
      recruitment and activation, islet vascular alterations, mainly at the level of
      post-capillary venules encircling the islets of Langerhans and a concomitant fall
      in Superoxide-dismutase (SOD) (the first cellular defence against free radicals)
      activity. These findings, together with the increase in vascular permeability and
      the morphological evidence of areas of oedema formation within the islets, have
      raised the interest in the "microvascular" approach to this disease. Actually the
      reduction in B-cell perfusion and the concomitant attack by phagocytes with a
      fall in SOD activity should be considered as events that are linked to each
      other. On the other hand both macrophages and endothelia are able to produce free
      radicals and, in particular, nitric oxide. This confirms that the islet vascular
      system seems to be involved in early insulitis and B-cell lysis.

PMID- 8305826
TI  - Exploitative competition in the chemostat for two perfectly substitutable
      resources.
AB  - After formulating a general model involving two populations of microorganisms
      competing for two nonreproducing, growth-limiting resources in a chemostat, we
      focus on perfectly substitutable resources. Leon and Tumpson considered a model
      of perfectly substitutable resources in which the amount of each resource
      consumed is assumed to be independent of the concentration of the other resource.
      We extend their analysis and then consider a new model involving a class of
      response functions that takes into consideration the effects that the
      concentration of each resource has on the amount of the other resource consumed.
      This new model includes, as a special case, the model studied by Waltman,
      Hubbell, and Hsu in which Michaelis-Menten functional response for a single
      resource is generalized to two perfectly substitutable resources. Analytical
      methods are used to obtain information about the qualitative behavior of the
      models. The range of possible dynamics of model I of Leon and Tumpson and our new
      model is then compared. One surprising difference is that our model predicts that
      for certain parameter ranges it is possible that one of the species is unable to
      survive in the absence of a competitor even though there is a locally
      asymptotically stable coexistence equilibrium when a competitor is present. The
      dynamics of these models for perfectly substitutable resources are also compared
      with the dynamics of the classical growth and two-species competition models as
      well as models involving two perfectly complementary resources.

PMID- 8305828
TI  - Extinction in predator-prey models with time delay.

PMID- 8305827
TI  - An epidemiological model for HIV/AIDS with proportional recruitment.
AB  - A model for HIV transmission is formulated for a homosexual population of varying
      size, with recruitment into the susceptible class proportional to the active
      population size and with stages of progression to AIDS. Analysis of this model
      includes identifying the threshold that determines whether the disease dies out
      or proportions remain endemic and establishing criteria that determine whether
      the population size decays asymptotically exponentially to zero or grows
      asymptotically exponentially to infinity. In an analogous heterosexual model, the
      conservation of heterosexual contacts is shown to imply that this two-sex model
      reduces to the one-sex model.

PMID- 8305829
TI  - On the formulation and computer implementation of an age-dependent two-sex
      demographic model.
AB  - A two-sex age-dependent demographic model is formulated within the framework of a
      stochastic population process, including both time-homogeneous and time
      inhomogeneous laws of evolution. An outline of the parametric components of the
      system, which expedite computer implementation and experimentation, is also
      given. New features of the model include a component for couple formation, using
      the class of Farlie-Morgenstern bivariate distributions to accommodate age
      preferences in selecting marriage partners, a component for couple dissolution
      due to separation or divorce, and an outline of techniques for initializing a two
      sex projection given scanty information. For the case of time-homogeneous laws of
      evolution, stability properties of two-sex models that are analogs of those for
      one-sex models are difficult to prove mathematically due to nonlinearities. But
      computer experiments in this case suggest that these properties continue to hold
      for two-sex models for such widely used demographic indicators as period crude
      birth rates, period rates of natural increase, and period age distributions,
      which converge to constant forms in long-term projections. The values of the
      stable crude birth rate, rate of natural increase, and quantiles of the stable
      age distribution differ markedly among projections that differ only in selected
      values of parameters governing couple formation and dissolution. Such
      experimental results demonstrate that two-sex models are not merely intellectual
      curiosities but exist in their own right and lead to insights not attainable in
      simpler one-sex formulations.

PMID- 8305830
TI  - Inhibition of carnitine palmitoyltransferase in normal human skeletal muscle and
      in muscle of patients with carnitine palmitoyltransferase deficiency by long- and
      short-chain acylcarnitine and acyl-coenzyme A.
AB  - The inhibition of total carnitine palmitoyltransferase (CPT) by short- and long
      chain acylcarnitine and acyl-coenzyme A (acyl-CoA) was studied in muscle
      homogenates of normal controls and of five new patients with CPT deficiency using
      the isotope forward assay. Acetylcarnitine inhibited neither normal CPT activity
      nor the CPT of patients. D,L-Palmitoylcarnitine almost completely inhibited CPT
      in patients but only 55% of normal activity. In controls the CPT fraction
      sensitive to inhibition by palmitoylcarnitine appeared to be identical with the
      fraction sensitive to inhibition by malonyl-CoA and succinyl-CoA, which probably
      represents CPT II. The abnormal inhibition of CPT by palmitoylcarnitine was more
      likely due to product inhibition than to a detergent effect. Acetyl-CoA
      concentrations up to 0.4 mM and palmitoyl-CoA above optimal substrate
      concentrations up to 0.3 mM both inhibited normal CPT by about 25%, whereas the
      CPT of patients was significantly more inhibited by both substances than was
      normal CPT. The inhibition by acetyl-CoA was probably due to the structural
      relationship with malonyl-CoA and succinyl-CoA. The abnormal inhibition of CPT in
      patients by palmitoyl-CoA was due either to an abnormal substrate inhibition or
      to a detergent effect on CPT II similar to that of Triton X-100. The data
      indicate that in CPT deficiency total CPT activity is normal under optimal assay
      conditions. CPT II, however, is abnormally inhibited by fatty acid metabolites
      that accumulate during fasting.

PMID- 8305831
TI  - Effects of therapeutic ribose levels on human lymphocyte proliferation in vitro.
AB  - Ribose has been used successfully in the treatment of ischemic heart disease and
      muscular enzyme deficiencies, and its administration also facilitates the
      diagnosis of coronary artery disease by influencing thallium-201 scintigraphy.
      Concerns about the safety of ribose therapy have been triggered by reports about
      inhibitory effects of ribose on cell proliferation in vitro. This study examines
      possible side effects of ribose on human lymphocytes. Unstimulated and mitogen
      stimulated human lymphocytes were incubated with ribose concentrations associated
      with high-dose oral administration, i.e., 3.5 mM, and with two- (7 mM) and
      tenfold (35 mM) higher concentrations. Cell cultures with matching glucose
      concentrations served as controls. Incorporation of [3H]thymidine into cells was
      used to measure cell proliferation. No significant inhibition of human lymphocyte
      proliferation in vitro was observed in mitogen-stimulated cells. Unstimulated
      cultures showed significant inhibition only at 35 mM ribose. It is concluded that
      ribose plasma levels associated with high-dose oral administration do not inhibit
      human lymphocyte proliferation in vitro. No evidence was found that short-term
      ribose therapy is harmful to human lymphocytes.

PMID- 8305832
TI  - Repeated complete remission in a patient with acute promyelocytic leukemia after
      treatment with 13-cis-retinoic acid first and with all-trans-retinoic acid in
      relapse.
AB  - The use of retinoic acid is a new approach in the treatment of acute
      promyelocytic leukemia. We outline the therapy in a 61-year-old patient with
      acute promyelocytic leukemia who had not responded to standard chemotherapy but
      in whom the administration of 13-cis-retinoic acid resulted in complete remission
      for 24 months. In relapse the patient was treated with all-trans-retinoic acid in
      combination with two cycles of daunorubicin and cytosine arabinoside and achieved
      another complete remission.

PMID- 8305833
TI  - Iatrogenic epidural spinal abscess.
AB  - We present four cases of iatrogenic epidural spinal abscess directly caused by
      externally introduced catheters or probes. In two patients the infection spread
      per continuum, in the other two patients due to haematogenous dissemination.
      Clinical presentation in each case included generalized malaise with fever, signs
      of meningeal inflammation and focal neurological signs at the spinal level. The
      diagnosis was made on the basis of inflammatory changes in the cerebral spinal
      fluid and localization of the abscess by means of computer and magnetic resonance
      tomography. A broad-spectrum antibiotic regimen included a penicillinase
      resistant preparation because of the frequent involvement of Staphylococcus
      aureus. It is our experience that a good outcome is dependent on early and
      specific treatment.

PMID- 8305834
TI  - Pulmonary tuberculosis due to bacille Calmette-Guerin.
AB  - Immunotherapy using bacille Calmette-Guerin (BCG) has gained increasing
      acceptance in the management of superficial bladder cancer. Systemic reactions
      after intravesical instillation of BCG are rare. However, when the therapy is
      complicated, the lung often becomes involved. Since the pathogenesis of lung
      infiltrates after immunotherapy is unknown, we report on a patient who developed
      a lung infiltrate after receiving BCG immunotherapy for bladder cancer. The
      infectious etiology was established by culture confirmation of a BCG strain in
      the bronchoalveolar lavage fluid.

PMID- 8305835
TI  - Instant therapy of acquired agranulocytosis and sepsis by recombinant granulocyte
      macrophage colony-stimulating factor in a polytrauma patient.
AB  - Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was
      given to an intensive-care patient with polytrauma in a life-threatening
      situation with acquired agranulocytosis and sepsis. Mature granulocytes
      reappeared in the blood 2 days after initiation of rhGM-CSF therapy; granulocyte
      precursors peaked at 43% after 5 days. Bone marrow examination performed 7 days
      after the beginning of rhGM-CSF therapy revealed complete regeneration of
      granulopoiesis. The functional analysis of these blood leukocytes in vitro showed
      regular production of reactive oxygen radicals. Clinically, the patient recovered
      without any serious side effects due to the rhGM-CSF therapy. These results
      suggest that rhGM-CSF accelerates granulocyte recovery from acquired
      agranulocytosis with the presence of their functional activity.

PMID- 8305836
TI  - Guillain-Barre syndrome following streptokinase therapy.
AB  - Clinical and laboratory data from a patient with Guillain-Barre syndrome
      indicated a probable etiological correlation of polyradiculitis to the
      intravenous administration of streptokinase. Oligoclonal IgG bands in the
      cerebrospinal fluid and serum were shown to be specific for streptokinase. Serum
      titers of streptokinase were elevated 64-fold for IgG, 16-fold for IgM, and 4
      fold for IgA compared to controls. Clinical symptoms of Guillain-Barre syndrome
      are thought to result from streptokinase antibody complex mediated damage to the
      local blood-nerve barrier. The pathogenic relevance of autoantibodies to albumin
      and proteins of the central and peripheral nervous systems, occurring early after
      onset of symptoms, remains to be determined.

PMID- 8305838
TI  - Mediation of immune glomerular injury.
AB  - Although glomerular disease remains the most common cause of end-stage renal
      disease worldwide, major advances have been made recently in understanding the
      cellular and molecular mechanisms which mediate these disorders. Nephrotic
      syndrome in non inflammatory lesions such as minimal-change/focal sclerosis and
      MN results from disorders of the GEC which can be simulated in animal models by
      antibodies to various GEC membrane epitopes. Clarification of how these
      antibodies effect the GEC to induce a loss of glomerular barrier function should
      substantially improve understanding of the pathogenesis of minimal change/focal
      sclerosis. In MN, proteinuria is mediated primarily by C5b-9 through similar
      mechanisms that also involve the GEC as a target. Inflammatory glomerular lesions
      are induced by circulating inflammatory cells or proliferating resident
      glomerular cells. Understanding of how these cells induce tissue injury has also
      evolved considerably over the past decade. Neutrophil-induced disease involves
      leukocyte adhesion molecules in regulating neutrophil localization; proteases,
      oxidants, and myeloperoxidase in mediating injury and platelets in augmenting
      these processes. The activated mesangial cell exhibits altered phenotype and
      proliferation with release of oxidants and proteases. Mesangial cell
      proliferation may be initiated by basic fibroblast growth factor and is
      maintained by an autocrine mechanism involving PDGF. TGF-beta is important in the
      subsequent development of sclerosis. As understanding of these areas evolves,
      numerous new therapeutic strategies can now be devised, including agents which
      block or inhibit complement effects, oxidants, proteases, growth factors, and
      other cytokines. Appreciation of the role of several natural inhibitors of these
      mechanisms may also allow therapeutic manipulations that upregulate regulatory
      proteins, with a consequent therapeutic benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305837
TI  - Thrombocytopenia induced by erucic acid therapy in patients with X-linked
      adrenoleukodystrophy.
AB  - Five patients with various clinical and genetic phenotypes of
      adrenoleukodystrophy were treated with a diet enriched with glycerol trioleate
      and glycerol trierucate (GTE). In all patients platelet counts decreased upon the
      administration of GTE, but no bleeding symptoms occurred in any of the patients,
      and bleeding time remained normal. Pseudothrombocytopenia was excluded in all
      patients. Thrombocytopenia was marked (84,000-37,000/mm) in three of the patients
      but was fully reversible after discontinuation of GTE. Mean platelet volumes were
      abnormally increased in all patients. When GTE was again administered by stepwise
      increasing the daily dose, platelet counts showed a clearly dose-dependent
      decrease. Bone marrow biopsies revealed no evidence of reduced
      megakaryocytopoiesis. The data indicate that in patients with
      adrenoleukodystrophy treated with GTE platelet counts should be closely monitored
      because thrombocytopenia may limit the maximal daily intake of GTE.

PMID- 8305839
TI  - Novel aspects of inflammation: interleukin-8 and related chemotactic cytokines.

PMID- 8305840
TI  - Potential role of chemotactic cytokines in glomerular injury.

PMID- 8305841
TI  - Immunogenetics of glomerulonephritis.

PMID- 8305842
TI  - Rapidly progressive glomerulonephritis: recent advances in pathogenesis,
      diagnosis, and therapy.

PMID- 8305843
TI  - Cellular and molecular pathomechanisms of diabetic nephropathy.

PMID- 8305844
TI  - Arterial hypertension and hyperlipidemia as determinants of glomerulosclerosis.
AB  - Arterial hypertension is a dominant pathogenetic factor for glomerulosclerosis.
      Nevertheless metabolic factors such as hyper- or dyslipoproteinemia may
      significantly modify and accelerate the process of glomerular scarring.
      Hyperlipidemia and lipoprotein abnormalities are often encountered in patients
      with nephrotic syndrome and chronic renal disease. Although the significance of
      lipid deposition in renal tissue and the role of lipoproteins in the pathogenesis
      of renal disease in man has not yet been clearly defined, experimental and
      clinical data indicate a damaging effect of disturbed lipid metabolism on the
      kidney. In humans glomerular lipid deposition is observed in several genetic
      diseases, including lecithin-cholesterol acyltransferase activity deficiency.
      Studies on animals with reduced renal mass, diabetes mellitus or arterial
      hypertension have shown that hypercholesterolemia increases the incidence of
      glomerulosclerosis. Especially the interaction of arterial hypertension and
      dyslipoproteinemia leads to a rapid and pronounced development of
      glomerulosclerosis. As most of these studies have been performed in the rat,
      which has a different lipoprotein profile than man, these results should be
      carefully interpreted with regard to their relevance for humans. In vitro cell
      culture studies on human glomerular cells have provided insight into the possible
      cellular mechanisms of lipid-induced glomerular damage. Apoprotein E containing
      lipoproteins that are pathologically elevated in many renal diseases are avidly
      taken up by human glomerular cells. Mesangial cells seem to play a central role
      in the initiation of glomerulosclerosis by proliferation and production of excess
      extracellular matrix. Lipoproteins are able to stimulate DNA synthesis in these
      cells and increase the synthesis of mitogens and matrix proteins. The
      pathogenetic role of modified, oxidized lipoproteins has not yet been
      elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305845
TI  - Glomerular disease of transplanted kidneys.

PMID- 8305846
TI  - Renal transport mechanisms for xenobiotics: chemicals and drugs.
AB  - Using the stopped flow tubular lumen or peritubular capillary microperfusion
      method, the apparent Ki values of a large number of organic anions and cations
      against the respective transport systems were evaluated. Thereby the luminal
      transport system for monocarboxylates (lactate), the contraluminal and luminal
      transport systems for dicarboxylates (succinate), sulfate, and hydrophobic
      organic cations (tetraethylammonium or N1-methyl-nicotinamide), as well as
      contraluminal transport system for hydrophobic organic anions (para
      aminohippurate, PAH) were characterized and their specificity determined. There
      is a partially overlapping substrate specificity between the PAH, dicarboxylate,
      and sulfate transport systems but also between the PAH and organic cation
      transport system. Xenobiotics and their metabolites are transported mainly by the
      organic anion (PAH) and organic cation transport systems. To test the complicated
      interactions possible a shot injection/urinary excretion method with simultaneous
      measurement of the intracellular concentration was developed. With this approach
      it is possible to evaluate (a) whether a substrate is net secreted or net
      reabsorbed, (b) whether interference with other substrates occurs, (c) whether
      interference takes place at the luminal or contraluminal cell side, and (d)
      whether cis-inhibition or trans-stimulation is the predominant mode of
      interaction. Finally, it will be discussed which ability a substrate must have to
      penetrate the cell membrane via a transporter, through the lipid bilayer, or
      both.

PMID- 8305847
TI  - Structural identification of brush border membrane transport systems--towards an
      understanding of regulatory mechanisms.
AB  - Until recently proximal tubular membrane transport systems were defined only on
      the basis of their function. However, in the past 4-5 years the use of molecular
      biology techniques has permitted structural identification of several proximal
      tubular transport systems. For example, sodium/D-glucose, sodium/phosphate, and
      sodium/sulfate cotransport systems have been identified. Also (a component of) an
      amino acid transport system accepting cystine and dibasic amino acids has been
      identified. These transport pathways may be targets for genetic alterations in
      proximal tubular solute reabsorption and/or be under physiological control.

PMID- 8305848
TI  - Cytostatics--induced tubular toxicity.

PMID- 8305849
TI  - Tubular injury in human kidneys: pathologic findings and pathogenic mechanisms.

PMID- 8305850
TI  - Regeneration of kidney tubular epithelial cells.

PMID- 8305851
TI  - Regulating factors of renal tubular hypertrophy.
AB  - Understanding the mechanisms of tubular hypertrophy is important because these
      cells simply represent the bulk of the nephron, and there is a convincing link
      between early tubular enlargement and the progression of renal disease. It seems
      reasonable to assume that cytokines and polypeptide growth factors including
      inhibitory factors such as TGF-beta induce in concert, rather than as single
      factors, tubular hypertrophy. The important observations that the activation of
      the intrarenal renin-angiotensin axis is altered in situations associated with
      renal growth, and that ACE inhibitors abolish compensatory hypertrophy in many
      models provided for us a basis for investigating the growth effects of ANG-II on
      cultured proximal tubular cells. ANG-II induces, as a single factor, tubular
      hypertrophy in vitro, and this growth effect has been studied in detail on a
      molecular levels. Endogenous induction of TGF-beta by ANG-II is important in the
      peptide-mediated hypertrophy. While some genes induced by ANG-II, such as
      immediate early genes, are engaged as part of a generalized activation of the
      nucleus, the hypertrophic effects may be mediated by a set of novel genes which
      may be part of an identifiable genetic program causing tubular enlargement. The
      identification of hypertrophy genes may offer new insight into the modulation of
      cytoplasmic enlargement and its interface with elements that control the cell
      cycle and may provide a tool for further therapeutic interventions.

PMID- 8305852
TI  - Identifying the genetic determinants of hypertension.

PMID- 8305853
TI  - Resolution of enantiomers of amino acids by HPLC.
AB  - Application of HPLC as a prime tool in the area of enantiomeric resolution has
      opened doors of success and varied interest. Use of chiral reagents either
      indirectly (as derivatization reagent) or directly (added to stationary or mobile
      phase) has led to achieve resolution of a wide range of compounds. Amino acids,
      being important molecules with simple structure and easy availability, have been
      extensively studied. A bibliographic survey on HPLC resolution of amino acids and
      derivatives along with a brief discussion on general methods of enantiomeric
      separation has been presented.

PMID- 8305854
TI  - Quantitation and identification of two cholecystokinin peptides, CCK-4 and CCK
      8s, in rat brain by HPLC and fast atom bombardment mass spectrometry.
AB  - A sensitive HPLC method has been described for quantitation of two
      cholecystokinin (CCK) peptides in discrete rat brain regions. Separation and
      quantitation was performed by the reversed-phase HPLC combined with
      electrochemical detection. Analytical recoveries of the tetrapeptide (CCK-4) and
      octapeptide-sulphate (CCK-8s) were 96% and 94%, respectively. The between assay
      coefficient of variation (CV) was less than 3% for both peptides. The within
      assay CV was 4% and 6% for CCK-4 and CCK-8s and the detection limit was 2 and 10
      pmol/mL, respectively. For identification of structures, the peptides were
      fractionated by semi-preparative HPLC using a novel SMART system for
      micropurification. The fractions were analysed by fast atom bombardment mass
      spectrometry (FAB MS) which confirmed the presence of both CCK-4 and CCK-8s in
      the rat brain tissue.

PMID- 8305855
TI  - Isolation and purification of amyloglucosidase from Halobacterium sodomense.
AB  - Amyloglucosidase from Halobacterium sodomense was purified by a combination of
      hydrophobic interaction chromatography and immobilized metal ion affinity
      chromatography at analytical and preparative scale with 75% recovery. The enzyme
      was found to be a dimer of two different subunits with molecular weights of
      72,000 and 82,000 D, respectively, combining in a 175,000 D native protein. The
      specific activity, KM, and amino acid composition of the enzyme was determined.

PMID- 8305856
TI  - Chromatographic determination method for 1-nitropyrene and its metabolites in
      biological samples with fluorescence detection after on-line reduction.
AB  - A high performance liquid chromatographic (HPLC) method with fluorescence
      detection after on-line reduction for the determination of 1-nitropyrene (NP), 1
      nitrosopyrene (NSP), 1-aminopyrene (AP) and N-acetylaminopyrene (AAP) has been
      developed. The reduction efficiency of NP and NSP on a zinc column was found to
      be higher than that of an electrochemical reducer. Using a HPLC system equipped
      with a zinc column (4.0 mm i.d. x 10 mm) and an imidazole/HClO4 (pH 6.8):
      acetonitrile mobile phase, detection limits (S/N = 3) of 20-30 fmol for NP, NSP
      and AP and 350 fmol for AAP were obtained. NP, NSP and AP were determined in the
      incubation mixture of NP and Salmonella typhimurium, YG1021, by this method. Time
      course studies showed that a large ratio of NP was metabolized in the pre
      incubation step of the Ames test.

PMID- 8305857
TI  - Measurement of ascorbic acid and dehydroascorbic acid in mammalian tissue
      utilizing HPLC and electrochemical detection.
AB  - Reliable measurement of the reduced and oxidized forms of ascorbic acid (AA) is
      challenging because they are highly reactive and unstable compounds. Detection of
      small amounts of AA and dehydroascorbic acid (DHAA) is essential for determining
      the biochemical function of the vitamin. While a variety of techniques exist for
      measurement of AA with detection limits in the millimolar range, a need exists
      for highly reliable assessment of picomolar levels of AA and DHAA in tissues. The
      present study presents a method for measuring AA and DHAA that combines high
      performance liquid chromatography with the advantages and increased detection
      limits and selectivity available with coulometric electrochemical detection. The
      difference between AA and "total AA" in tissue samples gives an assessment of
      DHAA concentration. Verification of the reliability of the assay is by the
      successful linear recovery of exogenously added AA and DHAA in tissue homogenate.
      Optimal conditions for reducing DHAA in tissue samples include a pH of 7.2,
      reaction time of 10 min, reaction temperature equal to room temperature, and a 10
      mM concentration of the reducing agent, beta-mercaptoethanol. AA and DHAA are
      measured in several mammalian tissues using the method presented.

PMID- 8305858
TI  - A simple method for plasma cannabinoid separation and quantification.
AB  - A sensitive (up to nanogram level) method for resolving a cannabinoid mixture in
      plasma is described. Cannabinoids were extracted with a C-18 Sep Pak cartridge
      and derivatized with dansylchloride. Then the derivatives were resolved on thin
      layer HPTLC silica plates which were developed and quantified by fluorescence
      densitometry at 340 nm.

PMID- 8305859
TI  - Derivatization with fluorogenic benzofurazan reagents of amino acid enantiomers
      and their separation on a Pirkle type column.
AB  - L- and D-Amino acids (Leu or Phe) were derivatized with fluorogenic reagents, 4
      fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), 4-(N,N-dimethylaminosulfonyl)-7
      fluoro-2,1,3-benzoxadiazole (DBD-F), 4-aminosulfonyl-7-fluoro-2,1,3
      benzoxadiazole (ABD-F) and 5-(N,N-dimethylamino)naphthalene-1-sulfonylchloride
      (DNS-CI), and separated on a Pirkle type column, Sumichiral OA 2500 (S) ((S)-1
      naphthylglycyl-3,5-dinitrophenylamide silica gel) with a mobile phase of 20 mM
      ammonium acetate in methanol. The fluorometric detection of the derivatives was
      made at 530 nm, 590 nm, 590 nm and 530 nm with excitation at 470 nm, 450 nm, 450
      nm and 350 nm, respectively. The former three derivatives of the enantiomers were
      separated well from each other; The alphas for each NBD-, DBD- and ABD-derivative
      of L- and D-Leu were 1.10, 1.11 and 1.10, respectively. However, the DNS
      derivatives of L- and D-Leu were not separated (separation factor, alpha = 1.0).
      All NBD-, DBD- and ABD-derivatives of L- and D-Phe were also well separated
      (alphas were 1.18, 1.17 and 1.16, respectively), while DNS-L- and -D-Phe were
      barely separated (alpha = 1.04). These data suggest that the 2,1,3-benzoxadiazole
      (benzofurazan) moiety is very effective and preferable to the
      dimethylaminonaphthalene sulfonyl (DNS) structure for the separation of
      enantiomers of amino acids derivatized with benzofurazan reagents.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8305860
TI  - [Post-transfusion purpura: clinical and immunologic studies in 38 patients].
AB  - BACKGROUND: Posttransfusion purpura (PTP) is characterized by severe
      thrombocytopenia and hemorrhagic diathesis about 1 week following blood
      transfusion. Only few studies exceed the description of single cases. MATERIALS
      AND METHODS: Clinical data from 38 patients were analyzed. Platelet antibodies
      were studied by complement binding, immunofluorescence, MAIPA assay and acid
      elution techniques. RESULTS: All patients were female. The mean age at onset was
      60.7 years (35-78 years). 4 patients received whole blood, 28 were transfused
      with packed RBC. 11 of 13 patients (85%) had febrile, non hemolytic adverse
      reactions during the transfusion. The interval between transfusion and onset of
      purpura extended from 2 to 14 days, with a peak at 7 and 8 days. Hemorrhagic
      symptoms lasted 10.1 days. The minimal platelet count was 7.0 x
      10(3)/microliters. The platelet count increased to over 50 x 10(3)/microliters
      after 13.9 days (n = 26), and to over 100 x 10(3)/microliters after 17.0 days (n
      = 22). 2 patients died of hemorrhagic complications. 24 patients were treated
      with glucocorticoids, 20 with intravenous immunoglobulins (ivIG), 17 of these
      received both therapies. 14 of 19 patients (74%) responded well to ivIG. In
      contrast, platelet transfusions produced no adequate increment, in 6 cases they
      provoked febrile reactions. 35 sera (92.1%) contained anti-Zwa, either alone or
      together with anti-HLA or in 1 case with anti-Bra. Anti-Baka and anti-Bakb were
      found in 1 case each. In 5 patients, anti-Zwa could be eluted from autologous Zwa
      negative platelets. CONCLUSIONS: The broad clinical spectrum of PTP could be
      shown. Since 5% of the patients succumb to bleeding complications, the
      application of ivIG as therapy of choice is recommended. The phenomenon of
      elution of alloantibodies from autologous platelets is interpreted as a
      consequence of 'pseudo-specificity' which may play a role in the pathogenesis of
      PTP.

PMID- 8305861
TI  - [Comparative study of blood and infusion heaters at various flow-through rates].
AB  - BACKGROUND: Transfusions of refrigerator-temperature blood, particularly when
      given very quickly, may induce severe hypothermia. In Germany, blood warmers used
      to avoid this danger mainly operate with dry heat. MATERIAL AND METHODS: In the
      current study we compared the Fenwal BW-5 (Travenol), the Biotest BW 385 and BW
      385L (Biegler) and the DW 1220 (American Pharmaseal) at different flow rates of
      packed cells and Ringer Lactate solution, respectively. RESULTS: Up to flow rates
      of about 30 ml/min higher transfusion temperatures were reached by the Biotest BW
      385L than by other warmers. Above flow rates of about 60 up to about 100 ml/min
      only the Fenwal BW-5 reached a transfusion temperature higher than 30 degrees C.
      CONCLUSIONS: For routine transfusions and infusions the Biotest BW 385L is the
      most suitable warmer. If a massive transfusion is necessary, it is recommendable
      to use two or three Fenwal BW-5 or to apply other technologies.

PMID- 8305862
TI  - [Physiology and clinical aspects of the extracellular bicarbonate pool: plea for
      cognizant use of HCO3-].
AB  - OBJECTIVE: Derived from literature data the function of bicarbonate (HCO3-) is
      described together with its extracellular pool, the regulating organs, and the
      clinical variations. DATA SOURCES AND SELECTION CRITERIA: The medical German and
      English literature was reviewed. No special literature retrieval was performed.
      Results from measurements at the author's laboratory were used. RESULTS: HCO3-
      may be described as the most potential nonrespiratory buffer base. For a 65 kg
      patient, the extracellular HCO3- pool amounts to approximately 350 mmol with a
      maximum tolerance limit of +/- 200 mmol. An influx of H+ ions (acidosis) and/or a
      reduction in the pCO2 (hyperventilation) will reduce this pool, whereas alkalosis
      and hypoventilation will enlarge it. The lungs (in close cooperation with the
      erythrocytes), liver and kidneys all contribute to the regulation of this HCO3-
      pool. The paramount organ for this regulation seems to be the liver, since it is
      able, even within a period of only a few hours, to eliminate much larger amounts
      of H+ ions (and correspondingly release HCO3-) than the kidneys are able to
      eliminate even under extreme conditions. It is primarily the liver which
      regulates the size of the HCO3- pool through the metabolism of the so-called
      metabolizable anions (bases) such as acetate, lactate, malate and citrate. The
      metabolism of these anions in the form of acetic, lactic, malic or citric acid
      requires (per mol) 1 mol H+ (acetate, lactate), 2 mol H+ (malate) or even 3 mol
      H+ (citrate), with the corresponding release of HCO3-. Iatrogenic alterations in
      the HCO3- pool occur more frequently than previously assumed. Infusion solutions
      may lead to a dilution acidosis (dilution of HCO3-), an infusion acidosis
      (addition of H+) or an infusion alkalosis (administration of metabolizable
      anions). CONCLUSION: An improvement in the declaration accompanying infusion
      solutions is recommended according to their actual pH-dependent composition. In
      particular, the concepts of base excess (BE, mmol/l) and BE pot. (mmol/l) should
      be introduced, in order to give an indication of potential alterations in the
      HCO3- pool after infusion and metabolism. This also applies to blood derivatives,
      where transfusion acidosis as well as alkalosis may occur, and in hemodialysis
      and peritoneal dialysis where the occurrence of acidosis and alkalosis during
      therapy need to be reckoned with.

PMID- 8305863
TI  - [Measuring errors in the determination of electrolyte concentrations with ion
      selective electrodes].

PMID- 8305864
TI  - [Gottardis M, Koller J, Benzer A, Wieser C, Hackl JM, Koenigsrainer A, Herold M,
      Fridrich L: Atrial natriuretic peptide (ANP), aldosterone, angiotensin II and
      renin in 'low T3 syndrome' in organ donors].

PMID- 8305865
TI  - [Monitoring by measurement of gastrointestinal mucosal pH value (pHi)].
AB  - Noninvasive measurement of mucosal pH by tonometry provides information on the
      adequacy of gastrointestinal mucosal oxygenation. The technique requires
      tonometer catheters (commercially available from Tonometrics) and a standard
      blood gas analyzer. After positioning of the catheter in the stomach or gut for
      at least 30 min, fluid is withdrawn from the prefilled balloon mounted on the
      catheter tip for pHi measurements. The pCO2 in the withdrawn fluid and
      bicarbonate concentration in the arterial blood are determined and pHi is
      calculated according to the Henderson-Hasselbalch equation. The tonometer
      technique has been validated in experimental studies and pHi has been shown to be
      a useful parameter to estimate adequacy of oxygenation of the mucosa surrounding
      the tonometer balloon. In surgical patients, pHi was found to be of high
      predictive value concerning incidence of complications; return of pHi towards
      higher values was found to be associated with a higher survival rate. In
      intensive care units, pHi-guided resuscitation proved to be superior to
      conventional therapy. Tonometric measurement of pHi is a useful parameter to
      monitor mucosal oxygenation and to provide information on the probability of
      complications and patient outcome. Further studies are needed in well-stratified
      patient groups with a present lower limit of pHi, triggering defined therapeutic
      interventions to improve mucosal oxygenation.

PMID- 8305866
TI  - [Microvascular monitoring using mercury in silastic strain gauge plethysmography
      (MSG)].
AB  - Mercury in silastic strain gauge plethysmography (MSG) is a noninvasive method
      for assessing microvascular parameters in peripheral limbs. MSG allows
      measurement of capillary filtration coefficient (Kf), isovolumetric venous
      pressure (Pvi), venous pressure (Pv) and arterial inflow (Qa) into the limb,
      respectively. We used MSG in combination with invasive monitoring techniques
      (pulmonary artery flotation catheters and arterial catheters) to study 36
      critically ill patients in either hemorrhagic or septic shock. We observed marked
      increases in Pvi in both patient groups which correlated with outcome. On
      admission, both groups showed elevated values for Pvi, survivors 37.7 +/- 2.6,
      nonsurvivors 33.7 +/- 3.5 mm Hg (mean +/- SEM) when compared with a control group
      of young healthy students (22.1 +/- 0.82 mm Hg). Survivors showed a decrease in
      Pvi to 27.3 +/- 1.7 mm Hg, whereas in nonsurvivors Pvi increased to 39.5 +/- 3.0
      at the last measurement taken. The changes in Pvi depended on the resuscitation
      regime used. On admission, patients requiring only fluid replacement (F) had a
      lower Pvi (31.3 +/- 2.9 mm Hg) than patients needing inotropic support with
      dobutamine (D, Pvi = 38.2 +/- 2.4 mm Hg) to fulfill our therapeutic goals (DO2 >
      550 ml.min-1 x m-2, VO2 > 150 ml.min-1 x m-2 and mixed venous lactate < 1.5
      mmol/l). After treatment Pvi did not change significantly in the F group (31.3 +/
      1.8), the D group however showed a significant decrease in Pvi to 25.4 +/- 2.42,
      which did not differ from the normal value. We regard Pvi as an indicator of
      insufficient microvascular flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305867
TI  - [Possibilities of cerebral monitoring].
AB  - Assessment of the level of cerebral function or of functional deficits,
      respectively, as in patients with acute cerebral lesions in coma, is the main
      purpose of cerebral monitoring. Although the clinical-neurological exploration of
      the patient with employment of scoring systems, such as the Glasgow Coma Scale,
      is the most comprehensive approach, it is of limited quantitative nature.
      Quantitative methods such as the EEG or evoked potentials are more objective,
      however, less comprehensive. Acute risks for the brain are increasingly evaluated
      in addition by direct or indirect measurements of the cerebral blood flow and O2
      uptake, using e.g. transcranial Doppler sonography, Hb/HbO2 spectroscopy, or HbO2
      saturation of cerebral venous blood for evaluation of cerebral O2 extraction.
      Recording of the intracranial pressure in comatose patients with severe head
      injury continues to play a central role in early recognition of fatal
      complications threatening the brain, such as an intracranial mass. Besides,
      assessment of the intracranial pressure is indispensable for selection of
      appropriate methods of treatment and adjustment of its necessary dose.

PMID- 8305868
TI  - [Monitoring intraoperative processing of acoustic stimuli with auditory evoked
      potentials].
AB  - 130 Patients undergoing elective intra-abdominal, gynaecological, urological or
      cardiac surgery were studied after institutional approval and informed consent.
      In all patients auditory-evoked potentials (AEP) were recorded in the awake state
      and during general anaesthesia. Latencies of the peaks V, Na, Pa, Nb and P1 were
      measured. V belongs to the brainstem-generated potentials, which demonstrates
      that auditory stimuli were correctly transduced. Na, Pa, Nb, P1 are generated in
      the primary auditory cortex of the temporal lobe. During anaesthesia with
      isoflurane, enflurane, thiopentone, etomidate and propofol the peak V remains
      unchanged, whereas the mid-latency auditory-evoked potentials (MLAEP) show marked
      increases in latencies and decreases in amplitudes or are even completely
      suppressed. This indicates a successful stimulus transmission up to the level of
      the brainstem and midbrain. However, stimulus processing in the primary auditory
      cortex is blocked. Under increasing end-expiratory concentrations of isoflurane
      MLAEP show a dose-dependent increase of latencies and decrease of amplitudes.
      Under surgical anaesthesia with 1.2 vol%, MLAEP are nearly completely suppressed.
      A different picture can be seen when MLAEP were recorded during anaesthesia with
      the receptor-specific anaesthetics midazolam, flunitrazepam, diazepam, fentanyl
      and ketamine. During anaesthesia with receptor-specific anaesthetics, the
      brainstem peak V as well as the mid-latency components remain nearly unchanged
      compared with AEP from awake patients. This indicates that auditory stimuli reach
      the primary auditory cortex and are processed at a primary cortical level. With
      increasing doses of fentanyl one can observe only a significant decrease of
      amplitudes for the late component P1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305869
TI  - cdc2a expression in Arabidopsis is linked with competence for cell division.
AB  - A key regulator of the cell cycle is a highly conserved protein kinase whose
      catalytic subunit, p34(cdc2), is encoded by the cdc2 gene. We studied the control
      of the expression of the Arabidopsis cdc2a gene in cell suspensions and during
      plant development. In cell cultures, arrest of the cell cycle did not
      significantly affect cdc2a mRNA levels, but nutrient conditions were important
      for cdc2a expression. During plant development, the pattern of cdc2a expression
      was strongly correlated with the cell proliferation potential. The effects of
      external signals on cdc2a expression were analyzed. Wounding induced expression
      in leaves. Lack of light altered temporal regulation of cdc2a in the apical but
      not root meristem of seedlings. Differential cdc2a responses were obtained after
      different hormone treatments. Signals present only in intact plants were
      necessary to mediate these responses. Although other control levels have yet to
      be analyzed, these results suggest that the regulation of cdc2a expression may
      contribute greatly to spatial and temporal regulation of cell division in plants.
      Our results also show that cdc2a expression is not always coupled with cell
      proliferation but always precedes it. We propose that cdc2a expression may
      reflect a state of competence to divide, and that the release of other controls
      is necessary for cell division to occur.

PMID- 8305870
TI  - rha1, a gene encoding a small GTP binding protein from Arabidopsis, is expressed
      primarily in developing guard cells.
AB  - The rha1 gene from Arabidopsis encodes a small GTP binding protein belonging to
      the Ypt/Rab family. Transgenic Arabidopsis plants containing the promoter region
      of the rha1 gene fused to the beta-glucuronidase (gus) reporter gene revealed gus
      expression limited mainly to the guard cells of stomata, the stipules, and the
      root tip of young plants. In flowering plants, expression was found predominantly
      in the receptacle and in guard cells of the different flower organs. High GUS
      activity could also be seen in callus tissue and developing seeds. No detectable
      activity was present in other plant tissues; activity could not be induced by
      various treatments. GUS activity was visualized histochemically using both 5
      bromo-4-chloro-3-indolyl beta-D-glucuronide and a newly developed GUS substrate:
      Sudan II-beta-glucuronide. The latter precipitates as red crystals at the site of
      GUS activity. Results obtained by the gus analysis were confirmed by whole-mount
      mRNA in situ hybridization. A hypothesis for the function of the Rha1 protein is
      discussed.

PMID- 8305871
TI  - S-RNase gene of Nicotiana alata is expressed in developing pollen.
AB  - In the solanaceous plant Nicotiana alata, self-incompatibility is controlled by a
      single, multiallelic locus (S locus) expressed in both pollen and pistil.
      Previously, we have shown cosegregation between alleles of the S locus and
      alleles of a gene that encodes a glycoprotein with ribonuclease activity (S
      RNase). Furthermore, expression of the S-RNase gene is apparently confined to the
      pistil and is correlated with the onset of self-incompatibility. In this paper,
      we report that the S-RNase gene is also expressed at low levels in developing
      pollen. A transcript in developing pollen hybridized to a cDNA encoding the S2
      RNase allele of the parent plant and did not hybridize to cDNAs encoding other S
      RNase alleles. Two cDNAs for the S2-RNase were cloned from a library derived from
      anthers of a plant homozygous for the S2 allele and both corresponded to the
      coding sequence of the S2-RNase. The product of the S-RNase gene was detected by
      immunocytochemistry in the intine of mature, hydrated pollen grains. These
      results are interpreted in the light of current knowledge of the structure of the
      S locus.

PMID- 8305872
TI  - Maize anthocyanin regulatory gene pl is a duplicate of c1 that functions in the
      plant.
AB  - Genetic studies in maize have identified several regulatory genes that control
      the tissue-specific synthesis of purple anthocyanin pigments in the plant. c1
      regulates pigmentation in the aleurone layer of the kernel, whereas pigmentation
      in the vegetative and floral tissues of the plant body depends on pl. c1 encodes
      a protein with the structural features of eukaryotic transcription factors and
      functions to control the accumulation of transcripts for the anthocyanin
      biosynthetic genes. Previous genetic and molecular observations have prompted the
      hypothesis that c1 and pl are functionally duplicate, in that they control the
      same set of anthocyanin structural genes but in distinct parts of the plant.
      Here, we show that this proposed functional similarity is reflected by DNA
      sequence homology between c1 and pl. Using a c1 DNA fragment as a hybridization
      probe, genomic and cDNA clones for pl were isolated. Comparison of pl and c1 cDNA
      sequences revealed that the genes encode proteins with 90% or more amino acid
      identity in the amino- and carboxyl-terminal domains that are known to be
      important for the regulatory function of the C1 protein. Consistent with the idea
      that the pl gene product also acts as a transcriptional activator is our finding
      that a functional pl allele is required for the transcription of at least three
      structural genes in the anthocyanin biosynthetic pathway.

PMID- 8305873
TI  - Role of the regulatory gene pl in the photocontrol of maize anthocyanin
      pigmentation.
AB  - The pl gene encodes a regulatory protein that controls the transcription of a
      number of structural genes of the anthocyanin biosynthetic pathway in maize. pl
      alleles have been classified phenotypically into two categories: dominant (Pl)
      alleles lead to intense, light-independent pigmentation in vegetative and floral
      organs of the plant; recessive "sun-red" alleles (pl) lead to light-dependent red
      pigmentation in which only tissues exposed to light become pigmented. Based on
      these observations, two alternate pathways leading to anthocyanin synthesis in
      the plant have been proposed: one requiring light and the other bypassing the
      light requirement through the action of Pl. To evaluate this hypothesis, we have
      analyzed light-independent and light-dependent alleles of pl. Sequence analysis
      revealed that the two types of alleles have very distinct promoters but have the
      capacity to encode very similar proteins. The protein encoded by one recessive
      allele was shown to be functional in transient assays. Measurements of husk mRNA
      levels by quantitative polymerase chain reaction showed that sun-red pl alleles
      are expressed at much lower levels than a Pl allele, but their expression is
      increased approximately sixfold by exposure to light. These results lead to the
      conclusion that the sun-red pl alleles are not null; instead, they synthesize
      functional mRNA and protein. We propose that the light-dependent pigmentation
      observed in pl plants is the result of a threshold effect in which light exposure
      boosts pl mRNA expression past a crucial level necessary to generate sufficient
      PL protein molecules to activate transcription of the anthocyanin structural
      genes.

PMID- 8305874
TI  - Chloroplast-encoded chlB is required for light-independent protochlorophyllide
      reductase activity in Chlamydomonas reinhardtii.
AB  - A chloroplast-encoded gene, designated chlB, has been isolated from Chlamydomonas
      reinhardtii, its nucleotide sequence determined, and its role in the light
      independent reduction of protochlorophyllide to chlorophyllide demonstrated by
      gene disruption experiments. The C. reinhardtii chlB gene is similar to open
      reading frame 563 (orf563) of C. moewusii, and its encoded protein is a homolog
      of the Rhodobacter capsulatus bchB gene product that encodes one of the
      polypeptide components of bacterial light-independent protochlorophyllide
      reduction. To determine whether the chlB gene product has a similar role in light
      independent protochlorophyllide reduction in this alga, a series of plasmids were
      constructed in which the aadA gene conferring spectinomycin resistance was
      inserted at three different sites within the chlB gene. The mutated chlB genes
      were introduced into the Chlamydomonas chloroplast genome using particle gun
      mediated transformation, and homoplasmic transformants containing the disrupted
      chlB genes were selected on the basis of conversion to antibiotic resistance.
      Individual transformed strains containing chlB disruptions were grown in the dark
      or light, and 17 of the 18 strains examined were found to have a "yellow-in-the
      dark" phenotype and to accumulate the chlorophyll biosynthetic precursor
      protochlorophyllide. RNA gel blot analysis of chlB gene expression in wild-type
      cells indicated that the gene was transcribed at low levels in both dark- and
      light-grown cells. The results of these studies support the involvement of the
      chlB gene product in light-independent protochlorophyllide reduction, and they
      demonstrate that, similar to its eubacterial predecessors, this green alga
      requires at least three components (i.e., chlN, chlL, and chlB) for light
      independent protochlorophyllide reduction.

PMID- 8305875
TI  - Synechocystis sp PCC 6803 strains lacking photosystem I and phycobilisome
      function.
AB  - To design an in vivo system allowing detailed analysis of photosystem II (PSII)
      complexes without significant interference from other pigment complexes, part of
      the psaAB operon coding for the core proteins of photosystem I (PSI) and part of
      the apcE gene coding for the anchor protein linking the phycobilisome to the
      thylakoid membrane were deleted from the genome of the cyanobacterium
      Synechocystis sp strain PCC 6803. Upon transformation and segregation at low
      light intensity (5 microE m-2 sec-1), a PSI deletion strain was obtained that is
      light tolerant and grows reasonably well under photoheterotrophic conditions at 5
      microE m-2 sec-1 (doubling time approximately 28 hr). Subsequent inactivation of
      apcE by an erythromycin resistance marker led to reduction of the phycobilin-to
      chlorophyll ratio and to a further decrease in light sensitivity. The resulting
      PSI-less/apcE- strain grew photoheterotrophically at normal light intensity (50
      microE m-2 sec-1) with a doubling time of 18 hr. Deletion of apcE in the wild
      type resulted in slow photoautotrophic growth. The remaining phycobilins in apcE-
      strains were inactive in transferring light energy to PSII. Cells of both the PSI
      less and PSI-less/apcE- strains had an approximately sixfold enrichment of PSII
      on a chlorophyll basis and were as active in oxygen evolution (on a per PSII
      basis) as the wild type at saturating light intensity. Both PSI-less strains
      described here are highly appropriate both for detailed PSII studies and as
      background strains to analyze site- and region-directed PSII mutants in vivo.

PMID- 8305876
TI  - Effect of transforming growth factor alpha, parathyroid hormone-related protein,
      or their combination on bone histomorphometry.
AB  - Transforming growth factor alpha (TGF alpha) has been implicated in the
      pathogenesis of inhibited bone formation in hypercalcemia of malignancy. We
      evaluated the effects of infusions of vehicle or TGF alpha (0.25 microgram/h), or
      parathyroid hormone-related protein (1-34) (PTHrP) (0.025 microgram/h) alone, or
      a combination of TGF alpha and PTHrP on bone histomorphometry in mice. The
      peptides were infused for 6 days via Alzet osmotic minipumps. TGF alpha alone,
      PTHrP alone, or a combination of the two resulted in an increase in bone
      resorption as well as bone formation parameters. The increase in bone formation
      with the combination of TGF alpha and PTHrP was significantly greater than that
      seen with either peptide alone. Therefore, it is unlikely that TGF alpha is the
      factor responsible for inhibited bone formation in hypercalcemia of malignancy.

PMID- 8305877
TI  - Heat-treated osteoblastic cell (ROS17/2.8)-conditioned medium induces the
      formation of osteoclast-like cells.
AB  - To study the effects of osteoblast products on osteoclast formation, we added the
      conditioned medium (CM) of rat osteoblastic cell line ROS17/2.8 to rat bone
      marrow cultures, in which tartrate-resistant acid phosphatase (TRAP)-positive
      osteoclast-like multinucleate cells (MNCs) formed in the presence of 10(-8) M
      1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The formation of 1,25(OH)2D3-dependent
      TRAP-positive MNC at day 7 of culture was strongly inhibited by the > 10 kDa
      fraction of ROS17/2.8 cell-CM (ROSCM), but heat treated ROSCM (htROSCM) expressed
      marked stimulation in the formation of the MNCs. The expression of several
      osteoclastic phenotypes of the MNCs induced by htROSCM and 1,25(OH)2D3 was more
      enhanced compared with that of the MNCs induced by 1,25(OH)2D3 alone. The MNCs
      induced by htROSCM and 1,25(OH)2D3 were highly motile, were sensitive to
      calcitonin (CT), and had high bone resorbing activity. These data suggest that
      htROSCM promotes the osteoclast differentiation in the presence of 1,25(OH)2D3 in
      a rat bone marrow culture system. The stimulatory activity of TRAP-positive MNC
      formation in htROSCM is derived from heat-stable protein(s) that is (are) thought
      to be different from colony-stimulating factors (CSFs) such as macrophage-CSF (M
      CSF) or granulocyte-macrophage-CSF (GM-CSF).

PMID- 8305878
TI  - Growth and development of bone mass in untreated alloxan diabetic rats. Effects
      of collagen glycosylation and parathyroid activity on bone turnover.
AB  - Body and skeletal growth and development were studied in alloxan-treated and age
      matched control rats, between 3 and 23 weeks of age. For both groups the growth
      of the skeletal and body weights were in phase, with a maximum at 7 weeks of age.
      The growth data was assessed according to Parks' theory of feeding and growth.
      Alloxan-treated rats showed an important reduction in body and bone mass, with a
      greater impact on soft tissues. As expected, the asymptotic body and skeletal
      weights were reduced respect to controls. The time needed to attain 63% of mature
      food intake (Brody's 'time constant') was also reduced, indicating that
      maturation occurred at an earlier age than controls. The diabetic state is
      characterized by a reduced food conversion efficiency. Despite hyperfagia,
      alloxan-treated rats showed circa one-half the body and skeletal weights of age
      matched controls. The following adverse effects of alloxan diabetes on bone
      tissue were observed: (a) a decrease in trabecular bone volume (femoral
      metaphyses) and cortical width (femoral diaphyses), (b) increased bone collagen
      glycosylation as a function of extracellular glucose concentration, (c) increased
      resistance of bone collagen to collagenase hydrolysis, (d) decreased rate of bone
      resorption except under strongly stimulated parathyroid function, (d)
      significantly lower ashes/bone matrix ratio in diabetic rats with more than 10
      weeks of diabetes, and (e) no histological evidence of osteomalacia.

PMID- 8305879
TI  - Ovariectomy-induced bone loss and the hematopoietic system.
AB  - To investigate the relationship of the hematopoietic system to the loss of bone
      due to ovarian hormone deficiency, we examined the effects of ovariectomy and
      estrogen administration on the thymus, spleen and the bone marrow, and on the
      proliferation of marrow progenitors of osteoclasts. We also assessed the effects
      of daily administration of interleukin-1 receptor antagonist (IL-1ra) on bone
      loss due to ovarian hormone deficiency. Ovariectomy resulted in decreased
      cancellous bone volume, increased trabecular osteoblast and osteoclast numbers,
      and increased serum alkaline phosphatase levels that were prevented by 17 beta
      estradiol treatment. Thymus weight, spleen weight, thymus and spleen lymphocytes,
      and bone marrow monocytes and lymphocytes also increased significantly following
      ovariectomy, and the increases were suppressed by 17 beta-estradiol. Ovariectomy,
      in addition, caused a 4-fold increase in the number of tartrate resistant acid
      phosphatase (TRAP)-positive multinucleated cells formed in cultures of marrow
      cells and the increase was partially inhibited by 17 beta-estradiol. IL-1ra
      administration did not prevent the bone loss due to ovariectomy. Our findings
      indicate that ovariectomy-induced bone loss in the rat is accompanied by marked
      changes in the hematopoietic system, and that these changes are modulated by
      estrogen administration. In spite of the negative finding with IL-1ra, the nature
      of the involvement of the hematopoietic system in the pathogenesis of bone loss
      due to ovarian hormone deficiency merits continued exploration.

PMID- 8305880
TI  - Effect of bound phosphoproteins and other organic phosphates on alkaline
      phosphatase-induced mineralization of collagenous matrices in vitro.
AB  - The aim of the present study was to determine to what extent the rate at which
      collagen mineralizes correlates with the amount and nature of bound phosphate
      groups. Sheets of collagen prepared from demineralized bovine dentin or cortical
      bone were complexed with various concentrations of phosphoserine [(P)Ser] or rat
      dentin phosphoproteins (PP; lowly or highly phosphorylated PP, LPP or HPP).
      Alternatively, phosphate groups were removed from the collagenous carrier
      material by treatment with phosphatases. Mineralization was achieved by
      incubation in culture medium supplemented with 45Ca, alkaline phosphatase and 10
      mM beta-glycerophosphate. The sheets were monitored for uptake of 45Ca and lag
      times calculated and plotted against the amount of bound phosphate. It was
      observed that dephosphorylation of the carrier causes an increase in lag time and
      that rat PP decreases lag times in a concentration-dependent way. HPP were more
      effective than LPP. (P)Ser or other small organic P-containing molecules had
      hardly any influence on lag time. It is concluded that next to the amount of
      bound phosphate, the nature of phosphorylated substances has considerable
      influence on the rate of mineralization of a collagenous carrier.

PMID- 8305881
TI  - A four-year longitudinal study of bone loss in patients with inflammatory bowel
      disease.
AB  - Serial measurements of spinal trabecular and radial cortical bone density were
      made over 4 years in 70 patients with inflammatory bowel disease. Mean rates of
      bone loss for the cohort differed little from rates reported in normal
      populations; however, some patients showed increased rates of loss, including
      patients whose bone density at entry to the study was already well below normal.
      There was a significant correlation between the amount of corticosteroid
      prescribed and spinal trabecular bone loss in males, but no significant
      correlation with other clinical parameters. Increased rates of bone loss
      emphasise the need for bone densitometry and prophylactic measures in patients
      with inflammatory bowel disease.

PMID- 8305882
TI  - Effect of vibrations on the organism--possibilities for development of non
      specific diseases and their prognostication.
AB  - Changes in the lipid metabolism, electrolytes, trace elements, acid-base balance
      in experimental animals and in workers exposed to vibrations, as well in patients
      suffering from vibration disease were investigated. The role of vibrations as a
      modifier of chemically induced cancerogenesis, and in implanted tumour cells was
      studied under laboratory conditions. A study was carried out on the morbidity
      with temporal work incapacity and total morbidity according to the turnover of
      the investigated groups (workers and patients suffering from vibration disease)
      in industrial branches with exposure to vibrations. Using statistical and
      mathematical methods of dispersion, correlation, factor and discriminant
      analysis, we detected interrelations between the investigated non-specific and
      specific indices of vibration exposure on the one hand, and possibilities for the
      development and the prognostication of cardiovascular, osteo-arthritic and other
      diseases and pathologic states, non-specific for vibration exposure, on the other
      hand.

PMID- 8305883
TI  - Experimental justification of the approach of medical genetics to individual
      prophylaxis of occupational diseases of respiratory organs.
AB  - The effect of inhalation of paprine dust on the bronchopulmonary tract and
      antibody-forming function of the spleen was studied experimentally on two lines
      of mice: CBA and CC57W, differing from each other by haplotype H-2 and
      antioxidant status of the organisms under study. During comparative
      histomorphological examination of lungs and bronchi of the experimental animals a
      more intensive reaction was found in mice of the CBA line, whereas in mice of the
      CC57W line vascular changes prevailed without any reactions in the bronchioles.
      Reactions of the spleen to paprine dust in animals of different lines were also
      different: the quality of antibody-forming cells in the spleen of CBA line mice
      with comparatively higher antioxidant status increased under experimental
      conditions, while it decreased in those of the CC57W line. The data obtained
      showed dependance of the sensitivity of the organism to action of operational
      dust on individual genetic properties, demonstrating thus the necessity of
      applying principles of medical genetics in order to prevent effectively the
      development of occupational diseases in exposed teams of workers.

PMID- 8305884
TI  - The role of the registry in the study of relation between cancer and environment
      experiences from Slovakia.
AB  - Highly complete and detailed data on cancer incidence collected in National
      Cancer Registry of Slovakia in the years 1968-1988 contributed largely to the
      study of the relations between cancer occurrence and environment. The study of
      temporal trends of age-adjusted rates revealed the rapid increase of overall
      cancer incidence and mortality rates in males influenced mainly by extreme
      increase and high proportion of lung cancer. The lower but increasing overall
      incidence rates in females could be related to the increase in breast, other skin
      and genital organs cancers, while the stabilized mortality trends were caused by
      improving prognosis of these major cancers in females. The possible role of
      environmental factors in adults could be stressed also by the temporal trends of
      childhood malignancies which remained fairly stable during the same period. The
      role of environmental factors in cancer etiology is further documented with the
      dramatically increasing incidence of malignant skin melanoma caused probably by
      the overexposition to the sunlight and with prevailing incidence of the majority
      of cancer sites in urban areas. Finally, the significantly increased incidence
      rates of other skin cancers are shown in two districts and in both sexes in
      relation to the environment, highly polluted with arsenic.

PMID- 8305885
TI  - Rapid species identification of wild mycobacterial isolates by monoclonal
      antibodies in ELISA.
AB  - An enzyme-linked immunosorbent assay (ELISA) for the identification of cultured
      mycobacteria belonging to the Mycobacterium tuberculosis complex and
      Mycobacterium kansasii originally described by R. Schoningh, C. P. J. H.
      Verstijnen, S. Kuijper and A. H. J. Kolk (1) was used for identification of
      mycobacteria from three week old primary cultures. A panel of six monoclonal
      antibodies (MoAbs) was used: two were specific for Mycobacterium tuberculosis (M.
      tuberculosis) complex, one for M. kansasii, one was directed against M. avium
      complex and two were broadly reacting with all mycobacterial species. The ELISA
      was introduced to a microbiology laboratory located in an area where M. kansasii
      infections are endemic. All acid-fast bacteria isolated from sputum samples over
      one month period were identified by ELISA and culture. All fifteen M.
      tuberculosis isolates and all seventeen M. kansasii were correctly identified by
      ELISA before culture results were known. Two of three M. avium complex strains
      could be identified in ELISA as belonging to the M. avium complex using the M.
      avium complex specific monoclonal antibody.

PMID- 8305886
TI  - Ostrava--a new endemic focus of Mycobacteria xenopi in the Czech Republic.
AB  - From February 1990 until late October 1991, M. xenopi was isolated from the sputa
      of 30 persons in one of the 4 boroughs of Ostrava. This species could also be
      identified in water samples and smears taken in 7 out of 14 tested households of
      both colonized persons and patients with mycobacteriosis xenopi. As established,
      the optimum conditions for multiplication of M. xenopi exist in exchanger units;
      control measures for this agent in the exchanger facilities are proposed.

PMID- 8305887
TI  - Influences of the environmental pollution on the immune system: some recent
      views.
AB  - The authors discuss the contemporary progress in preventive immunology with
      special attention to unfavourable effects of environmental pollution. They
      followed-up these problems systematically for more than twenty years and in this
      paper they present some of their results. They stress the importance of the
      protective effect of balanced nutrition with an adequate supply of vitamins and
      trace elements. The unfavourable effect of pollution is documented by different
      health aspects of the population living in the heavily polluted region of
      Northern Bohemia.

PMID- 8305888
TI  - Chemical risk assessment and management in Czech and Slovak Republics.
AB  - For more than 40 years, former Czechoslovakia has made minimal efforts to protect
      the environment. As a result, newly formed republics suffer from some of the
      worst environmental pollution in Europe. In all stages of a complex process of
      improving chemical safety both countries are facing tremendous problems: lack of
      efficient and powerful legislative measures, inadequate and sometimes non
      reliable data, shortage of sophisticated equipment, virtual absence of basic
      knowledge and, generally, persisting distrust between public and governmental
      institutions in health and environmental issues. These factors have made the
      beginning of new approaches extremely difficult. However, a great effort of many
      people in both republics together with a substantial assistance of both
      international organizations and national institutions from developed countries
      seem to be promising. It could help to move former position of largely
      ineffective measures and investments to one where limited funds are spent to
      achieve public benefits.

PMID- 8305889
TI  - The effect of cigarette smoking on the indexes of immunity and acute phase
      reaction in subjects with occupational exposure to organic solvents.
AB  - The study was carried out in 156 men, including 49 nonsmokers and 47 smokers who
      had never been exposed to chemicals, 19 nonsmokers exposed to organic solvents,
      and 41 smokers exposed to organic solvents. The results of toxicological analysis
      of air in the working place carried out in the range depending on the type of
      solvents used in the process of lacquering of steel cans and on the data obtained
      from the producer showed that the solvents contained benzene, toluene, xylene and
      their derivatives partly hydrogenated, paraffin hydrocarbons, oleins, naphthenes
      (components of painter's naphtha), monohydric and polyhydric alcohols (butanol,
      cyclohexanol, butyloglycol), esters (ethylglycol acetate, butyl acetate) and
      ketones (methyl isobutyl ketone, cyclohexanone). Measured benzene concentrations
      varied from 0 to 370 mg x m-3 (0 to 116 ppm), with arithmetic mean annual
      averages of about 100 mg x m-3 (31 ppm) in the late 1960's and less than 50 mg x
      m-3 (16 ppm) in the 1970's. In the 1980's values for the TWA were 0-38 mg x m-3
      (0-12 ppm) with arithmetic mean averages of about 19 mg x m-3 (6 ppm) and for the
      level of benzene 0-351 mg x m-3 (0-110 ppm), with arithmetic mean annual averages
      of about 48 mg x m-3 (15 ppm). Phenol concentration in the urine of the workers
      in groups was 7.9 +/- 3.5; 10.0 +/- 5.8; 16.8 +/- 6.2 and 18.4 +/- 9.7 mg x 1(-1)
      respectively. Hippuric acid concentration in the urine of the workers in groups
      was 496 +/- 326, 538 +/- 341, 982 +/- 420 and 1107 +/- 507 mg x 1(-1)
      respectively. The parameters of immunity and proteins acute phase reaction were
      determined, measuring the count of T, B, and "non-T, non-B" circulating
      lymphocytes, the concentration of immunoglobulins, lysozyme, C3c, C4, alpha 1
      acid glycoprotein, haptoglobulin and ceruloplasmin in serum. The results of the
      presented study suggest the role of cigarette smoking as a co-factor in the
      immunological changes brought out by occupational exposure to organic solvents.
      This phenomenon is reflected in the changes of IgA, IgD, IgG, IgM and lysozyme in
      the serum, and number of circulating T cells.

PMID- 8305890
TI  - Study of human exposure to ochratoxin A and assessment of possible sources.
AB  - The first study carried out in the CSFR covered 644 samples of blood sera from
      the district of Uherske Hradiste (about 1,000 km2 and 150,000 population) during
      March-May 1990. The samples from the selected persons (over 18 years of age) were
      collected within 4 sampling weeks. Ochratoxin A (OA) was established
      densitometrically after the minicolumn separation with HPTLC. The detection limit
      was about 0.5 microgram OA/l, recovery about 95%. The maximum established value
      was 12 micrograms OA/l. The value 1 microgram OA/l was exceeded by 12.4% of
      samples. Seventy-eight per cent of samples were under the detection limit. After
      stratification of the experimental group (according to sex and age) higher
      numbers of findings above 1 microgram OA/l were found in the stratum of 30-40
      years (males and females) and in the age group over 60 (females). The differences
      were statistically insignificant (contingency table analysis, alpha > 0.10). The
      high statistical significance (contingency table analysis) of difference (alpha <
      0.01) showed the findings over 1 microgram OA/l, and the date of the sampling
      week. The graphic analysis (localisation of the results in the map of the area)
      did not support the hypothesis of the dependence of the results over 1 microgram
      OA/l on the place of residence. The results do not support the hypothesis on the
      sites with a higher level of OA contamination in the studied district. We assume
      the OA hazard sources originating from both the individual and communal food
      supply.

PMID- 8305891
TI  - Metabolism and effect of nitrates.
AB  - The effect of nitrate on the health of mice in a long term study is described.
      Nitrate was given to the mice in the form of calcium nitrate in drinking water in
      varying concentrations, and the mice were observed over the course of 18 months.
      Three groups were formed: 1. control group, 2. group I (100 mg nitrate/l drinking
      water) and group II (1,000 mg nitrate/l drinking water). The parameters studied
      were liver function, kidney function, total iron, ammonium, total protein and
      electrophoresis of the various serum proteins, body weight, and N-glycolyl
      neuraminic acid as a tumor marker. Nitrate is broken down via nitrate,
      hydroxylamine to ammonium and finally to urea. The concentration of urea
      increased with time and higher concentrations of nitrate load. The exposed mice
      clearly lost weight and died prematurely. This was true only for the mice in
      group II. With a load of 100 mg/l drinking water, no change in the physiological
      parameters could be seen within the time period studied.

PMID- 8305892
TI  - A history of poliomyelitis in the Czech Republic--Part I.
AB  - The incidence of poliomyelitis in the Czech Republic shows four epidemiologically
      different phases recorded during a lifetime of one human generation: endemicity
      (until 1938), epidemicity (1939 to 1956), repression (1957 to 1960) and
      elimination (1961 till now). The phase of the endemic incidence of poliomyelitis
      studied in this paper finished in 1938. Since 1919 when poliomyelitis
      notification was started, three waves of increasing though low mortality were
      observed: in 1926, 1932 and 1936 (0.27, 0.43 and 0.38 per 100,000, respectively).
      Between 1919 and 1938 the mortality increased in children over one year but it
      remained relatively highest in infants under one year of age. The poliomyelitis
      death rates were high between 1928 and 1938, 23.6% on the average. Such high
      rates might be attributable to the underrated morbidity cases in comparison with
      a rather reliably notified polio mortality. The period between 1919 and 1938
      represented the end of the endemic incidence of poliomyelitis in the Czech
      countries, and it could be considered as preepidemic.

PMID- 8305893
TI  - Hospital waste management practice in the Czech Republic.
AB  - Hospital wastes pose a serious problem. This is primarily caused by the diversity
      of the individual components of the waste which constitute a risk to health if
      inadequately handled. It is evident that economic and technical conditions for
      both a safe disposal as well as efficient steam sterilization and management
      practice based on legal regulations consequently will contribute to protections
      of both human health and the environment.

PMID- 8305894
TI  - WHO programme on air quality and air pollution epidemiology.

PMID- 8305895
TI  - Characteristic features of HIV/AIDS in the Czech Republic.
AB  - First laboratory proved HIV infections in the Czech Republic were diagnosed in a
      homosexual couple in autumn of 1985. Total number of detected HIV+ cases reached
      143 persons by the end of 1992 (132 men and 11 women), of that 31 cases were
      classified as fully blown AIDS (21 already died). Out of these 143 HIV+ cases, 93
      (65.0%) are represented by homo/bisexuals, 10 (7.0%) by heterosexuals, 16 (11.2%)
      by haemophiliacs, 14 (9.8%) by blood recipients, 1 (0.7%) by IVDU and 9 (6.3%) by
      unknown transmission category. Approx. 2.1 mil. of tests have been done as
      routine screening of donated blood. Only 5 cases (0.0002%) of HIV positivity have
      been found in this group. All HIV positive blood recipients (30 cases) were
      infected before the mandatory HIV testing of blood supply has been introduced in
      1987 (14 out of 16 HIV+ haemophiliacs were infected by imported clotting
      products). The twins born in 1990 to mother infected by contaminated blood in
      1984, were declared at the age of 30 months as HIV free, with all laboratory
      tests (serology, virus cultivation, PCR) negative. The cummulative infection rate
      of HIV antibody in 1986-1992 reached 13.8 per million inhabitants. It may be
      concluded that slow steady increase in the number of reported HIV/AIDS cases has
      been registered during the whole follow-up period. The authors are aware that
      relatively low prevalence of HIV infection in the Czech Republic may change
      dramatically in consequences of recent deep social, political and economical
      changes in the country.

PMID- 8305896
TI  - Synaptotagmin: a Lambert-Eaton myasthenic syndrome antigen that associates with
      presynaptic calcium channels.
AB  - Plasma from patients with Lambert-Eaton myasthenic syndrome (LEMS), an autoimmune
      disease of neuromuscular transmission, contains antibodies that immunoprecipitate
      125I-omega-conotoxin GVIA labeled-calcium channels solubilized from rat brain.
      These antibodies label a 58-kDa protein in Western blots of partially purified
      125I-omega-conotoxin receptor preparations. Monoclonal antibody 1D12, produced by
      immunizing mice with synaptic membranes, has similar properties as these LEMS
      IgG. 1D12 antigen was purified by immunoaffinity chromatography and shown to bind
      LEMS IgG. The antigen was identified by immunoscreening a rat brain cDNA library
      with mAb 1D12 and found to have strong homology to the synaptic vesicle protein
      synaptotagmin. These antibodies immunoprecipitate calcium channels by binding to
      synpatotagmin, an associated protein. We suggest that the interaction between
      synaptotagmin and omega-conotoxin sensitive calcium channels plays a role in
      docking synaptic vesicles at the plasma membrane prior to rapid neurotransmitter
      release. Autoantibody binding to a synaptotagmin-calcium channel complex may be
      involved in the etiology of LEMS.

PMID- 8305897
TI  - Lack of involvement of [Ca2+]i in the external Ca(2+)-independent release of
      acetylcholine evoked by veratridine, ouabain and alpha-latrotoxin: possible role
      of [Na+]i.
AB  - Synaptosomes were challenged by veratridine, ouabain and alpha-latrotoxin, and
      the release of 14C-acetylcholine (ACh) was measured in the absence of external
      Ca2+. We wished to test whether Ca2+ mobilized from internal stores triggered the
      ACh release that was independent of external Ca2+. We found that none of the
      agents altered the [Ca2+]i in a Ca(2+)-free medium. Buffering the intracellular
      Ca2+ concentration with BAPTA did not prevent the increase in release of 14C-ACh
      by veratridine or ouabain in the absence of Ca2+, however, it greatly reduced the
      release evoked in a Ca(2+)-containing medium. In parallel samples the release of
      ACh and the change in the internal Na+ concentration ([Na+]i) were measured. It
      was found that veratridine, ouabain and alpha-latrotoxin all enhanced [Na+]i in a
      concentration-dependent manner and a good quantitative relationship existed
      between the increase in [Na+]i and the release of ACh.

PMID- 8305898
TI  - Analysis of the structure and expression of the VAMP family of synaptic vesicle
      proteins.
AB  - VAMP/synaptobrevin proteins were first discovered as small integral membrane
      proteins in synaptic vesicles of vertebrates and invertebrates. At least two
      isoforms are expressed in the central nervous system of mammals in non
      overlapping patterns. Biochemical studies have revealed that the VAMP synaptic
      vesicle proteins are the specific target in the presynaptic nerve terminal of
      botulinum B neurotoxin and tetanus toxin metalloendoprotease activities. The fact
      that these toxins rapidly and completely abrogate neurotransmission suggests that
      VAMP proteins play an essential role in this process. More recently,
      immunologically related proteins have been identified in non-neuronal cells such
      as adipocytes. In addition, molecular genetic studies of yeast secretion have
      identified VAMP-related proteins as playing important roles in vesicular
      transport between the endoreticulum and Golgi. Taken together, these results
      suggest that the VAMP proteins found on synaptic vesicles might represent
      specialized forms of proteins which participate in general aspects of cell
      membrane trafficking.

PMID- 8305899
TI  - Fluorescence approaches to the study of the actin-nucleating and bundling
      activities of synapsin I.
AB  - Synapsin I is a neuron-specific phosphoprotein which binds to small synaptic
      vesicles and actin in a phosphorylation-dependent fashion. We have analyzed the
      ability of synapsin I to interact with actin monomers and filaments using
      purified proteins derivatized with fluorescent probes. Synapsin I accelerates the
      initial rate of actin polymerization and increases the final steady-state levels
      of polymerized actin. The fraction of total actin polymerized by synapsin I
      strongly depends on the synapsin I-actin ratio. We have visualized the actin
      bundling activity of synapsin I using a non-perturbing method, video-enhanced
      microscopy of fluoresceinated synapsin I and actin filaments. Our findings
      suggest that synapsin I exerts a control on the physical characteristics of the
      cytoskeletal network of the nerve terminal and are consistent with the proposed
      role of synapsin I in mediating the interaction of synaptic vesicles with actin.

PMID- 8305900
TI  - Functional relevance of presynaptic muscarinic autoreceptors.
AB  - Pre- and postsynaptic muscarinic receptors have been characterized in the
      isolated trachea and ileal circular muscle of the guinea pig. The muscarinic
      autoreceptors mediating inhibition of acetylcholine release in the circular
      muscle belong to the M1 subtype, whereas those inhibiting acetylcholine release
      in the trachea are M2 or M4 receptors. In both tissues the postsynaptic
      muscarinic receptors are M3 receptors. Blockade of the autoreceptors by selective
      M1 and M2/M4 receptor antagonists leads to facilitation of cholinergic
      neurotransmission.

PMID- 8305901
TI  - HIV infection and AIDS among drug injectors at Rio de Janeiro: perspectives and
      unanswered questions.
AB  - Data from various countries show considerable variation in the rate of spread of
      the human immunodeficiency virus (HIV) among drug injectors. Although further
      research is needed to predict the rate of increase of seroprevalence at Rio de
      Janeiro, preliminary data confirm the presence of the virus, with a
      seroprevalence of about 33 per cent in 1990. Issues arising from research into
      the probable determinants of viral spread among the thousands of drug injectors
      in the city are outlined in the present paper. Even before the research is
      completed, however, it is clear that interventions are needed to reduce further
      viral transmission both among drug injectors and from them to their sexual
      partners and offspring. Efforts should be made to prevent the population at risk
      from initiating the practice of drug injection, and to promote a major expansion
      in drug abuse treatment facilities. Drug injectors should also be encouraged to
      reduce the risk of their becoming infected or passing on the virus to others,
      through educational outreach, through the distribution of supplies that
      facilitate risk reduction (bleach, syringes, condoms), and through innovative
      approaches to behaviour change.

PMID- 8305902
TI  - Transmission of HIV among drug addicts in three French cities: implications for
      prevention.
AB  - In 1988, the Institute for Epidemiological Research on Drug Dependence conducted
      an ethnographic study designed to assess the results of liberalization of the
      sale of syringes. In that study, drug addicts were found to have gradually
      altered their customary practices by limiting the sharing of syringes. Two years
      later, a second study was conducted to further assess the behavioural changes
      under way. The whole survey covered 359 subjects--165 in Paris, 110 at Marseille
      and 93 at Metz. Almost all the subjects stated that they knew about the risks of
      transmission of the human immunodeficiency virus (HIV) by needle and during
      unprotected sexual intercourse. Almost all of them (98 per cent) knew that
      syringes were freely sold at pharmacies. Most of them (84 per cent) felt that
      they were generally well informed on the subject of AIDS and the ways in which
      the virus was transmitted. Prostitutes accounted for 17 per cent of the sample,
      with more women (32 per cent) than men (13 per cent) included in that category.
      The overwhelming majority of the subjects bought their syringes at pharmacies,
      and the trend towards the non-sharing of syringes was confirmed, a change in
      behaviour that has emerged mainly since 1987. Among the "new generation" of drug
      addicts, namely those who began to inject after 1987, the changes are reflected
      in a much lower rate of infection--2 per cent instead of 28 per cent of the
      total. About a third of the subjects, however, continued to engage in practices
      involving a certain level of risk. In a global context, including subjects who do
      not know how to properly clean a syringe, a variety of usually ineffective
      practices are followed, for example rinsing with water, lemon juice, or scent.
      The use of bleach remained limited, and few people considered cleaning with it.
      Liberalization of the sale of syringes seems to be essential to the prevention of
      AIDS among drug addicts. But this measure is not enough in itself. Apart from the
      overall problems of looking after the health of drug addicts and ensuring access
      to medical care, certain specific measures remain highly desirable. Of particular
      importance is the dissemination of information clearly describing effective
      methods of sterilizing syringes (including the use of bleach).

PMID- 8305903
TI  - HIV infection among drug abusers in the Belgrade area.
AB  - The abuse of heroin and other opiates by intravenous injection is identified as
      the major risk for the spread of infection by the human immunodeficiency virus
      (HIV) and of acquired immunodeficiency syndrome (AIDS) to the population at
      large. From 1980 to 1992, 2,712 opiate-addicted intravenous drug users with
      severe complications and behavioural problems were treated at the Institute on
      Addictions, Belgrade; 2,090 of them were from the Belgrade area and 622 from
      other urban areas. All of them had used heroin by intravenous injection during a
      certain period of their addiction careers. A majority of the patients had started
      using heroin by the age of 20, and begun treatment after six or more years of
      addiction. An informal survey of heroin-addicted intravenous drug users newly
      admitted for treatment showed that every respondent knew from 10 to 20 other
      heroin users who had not sought treatment. It was estimated that a majority of
      intravenous drug users may not have been known to the authorities. Of 551
      intravenous-opiate-addicted patients from the Belgrade area tested between 1987
      and 1992, 43.7 per cent were HIV-seropositive, or 47.9 per cent of HIV
      seropositive males and 32.9 per cent of females, while for the same period, of
      366 tested patients from other urban areas, 4.6 per cent were HIV-seropositive,
      5.2 per cent of them males and 1.8 per cent females. The distribution by sex of
      the intravenous-opiate-addicted patients indicated that the percentage of females
      who started using heroin earlier in their lives and the percentage of those who
      sought treatment late--after six or more years of addiction--were higher than the
      corresponding percentages of males. Also, female patients tended to become
      infected with HIV earlier in their lives than male patients.

PMID- 8305904
TI  - An international comparative study of HIV prevalence and risk behaviour among
      drug injectors in 13 cities. WHO Collaborative Study Group.
AB  - Although reported rates of human immunodeficiency virus (HIV) infection and
      related risk behaviours among drug injectors vary considerably throughout the
      world, and comparison of findings is often hampered by methodological variability
      among centres. In 1989 the World Health Organization initiated a comparative
      study of current drug-injecting behaviour and HIV infection using a standardized
      methodology. Centres were asked to recruit at least half of their samples outside
      drug treatment settings in order to achieve as representative a group of
      injectors as possible. Respondents were interviewed using a questionnaire
      designed by an international working group, and they were asked to provide blood
      and/or saliva specimens for voluntary testing. Data from 13 centres (Athens,
      Bangkok, Berlin, Glasgow, London, Madrid, Naples, New York, Rome, Rio de Janeiro,
      Santos, Sydney and Toronto) are reported here. A total of 6,390 injectors were
      recruited to the study from October 1989 to March 1992, with sample sizes ranging
      from 85 at Santos (Brazil) to 1,300 in New York. Weekly or daily sharing of
      injecting equipment was reported by less than a quarter of injectors in all
      centres. A high proportion of those sharing made some effort to clean equipment
      before use, although not always by efficient methods. In all centres, the
      majority of respondents were sexually active; however, rates of unprotected
      sexual intercourse were high, particularly between regular sexual partners. The
      overall HIV prevalence rate was 22 per cent, ranging from 0 per cent in Athens to
      60 per cent in Santos. Caution should be exercised in postulating a link between
      HIV prevalence and current risk behaviour, particularly since injectors appear to
      behave in similar ways across a diverse range of study locations. This is the
      first report on an international collaborative study for which a large number of
      injectors were successfully recruited from a variety of settings. The wealth of
      data now available provides a greater understanding of the social epidemiology of
      drug injecting, which is essential for the implementation and evaluation of
      campaigns and interventions designed to limit the spread of HIV infection.

PMID- 8305905
TI  - The global diffusion of injecting drug use: implications for human
      immunodeficiency virus infection.
AB  - Long-standing patterns of drug injecting in mainly developed countries have been
      joined by the introduction and expansion of drug injecting in developing
      countries, often followed quickly by outbreaks of human immunodeficiency virus
      (HIV) infection. Drug injecting has been identified in 80 countries and HIV
      infection in 52 of these. Given the continued recruitment of new injectors where
      injecting is endemic, the diffusion of drug injecting in countries where the
      practice was formerly rare and the potential for this diffusion to occur, HIV
      prevention must also consider interventions that discourage drug injecting.
      Particularly at risk are countries in drug-producing regions and along drug
      transit routes in Africa, south-east and south-west Asia and South America.
      Injecting can spread in less time than it takes to introduce HIV prevention
      activities. The task of the public health system will be to find a balance
      between activities targeted at helping current injectors change their behaviour
      and activities targeted at discouraging the adoption of drug injecting.

PMID- 8305906
TI  - Strategies for the prevention of HIV infection among and from injecting drug
      users.
AB  - Despite a substantial reduction in the level of high-risk behaviours among
      injecting drug users (IDUs) documented in an impressive number of studies from
      many countries, human immunodeficiency virus (HIV) infection continues to spread
      among and from this population, reflecting the high baseline levels of these risk
      behaviours before the epidemic. In many countries, the control of HIV spread
      among IDUs is critical to efforts to control the epidemic in the population as a
      whole. Although the evaluation of individual or multiple strategies is
      problematic, there is accumulating evidence and increasing confidence that the
      course of the epidemic can be altered by implementing some or all of a range of
      strategies. Authorities mindful of their public health responsibilities should
      estimate the risk of spread of HIV among and from IDU populations in their
      jurisdiction and plan their response accordingly by selecting prevention measures
      that are appropriate for local conditions and by vigilantly monitoring
      developments.

PMID- 8305907
TI  - Critical issues regarding AIDS among injecting drug users.
AB  - The paper identifies and reviews some critical issues in the field of human
      immunodeficiency virus (HIV) transmission among intravenous drug users. First, it
      discusses political denial and compartmentalization of the problem, giving an
      example from the United States that illustrates the lack of a coherent national
      strategy. It then reviews the role that stereotypes play in policy-making and
      points out that behaviour change can be considerable, giving details of
      successful safer injection programmes. The conditions that foster injection as a
      mode of ingesting drugs are reviewed, as in the role of drug trans-shipment
      patterns, particularly as a possible conduit of HIV. Finally, the role of prisons
      as places for the spread of HIV, and therefore for its prevention, is discussed.

PMID- 8305908
TI  - Drug injecting and HIV infection among the population of drug abusers in Asia.
AB  - Opium has been produced and consumed since the nineteenth century in the areas of
      Asia currently referred to as the Golden Crescent and the Golden Triangle. In the
      1970s and 1980s, most countries from Afghanistan to Japan experienced a heroin
      epidemic of varying degrees of severity. Opium and heroin abuse appeared to be
      more severe in countries and areas where those drugs were produced, an exception
      being Hong Kong, which has had a large population of heroin abusers for more than
      two decades. Drug injecting was far more common in countries of the Golden
      Triangle than in those of the Golden Crescent. In Myanmar and Thailand, for
      example, up to 90 per cent of chronic heroin abusers practised intravenous
      injection, which appeared to spread to heroin abusers in nearby territories such
      as the State of Manipur in India. Yunnan province in China, as well as Malaysia
      and Viet Nam. Amphetamine abuse was more frequent in Japan and the Republic of
      Korea for a number of years, while illicit production and consumption in the
      Philippines have recently shown significant increases. The injection of
      amphetamines was common only in the Republic of Korea. The prevalence of
      injecting among institutionalized methamphetamine abusers was reported at about
      90 per cent. Most countries in Asia first reported cases of infection with the
      human immunodeficiency virus (HIV) in the mid-1980s. An extremely rapid spead of
      the epidemic and high prevalence, at rates of from 30 to 90 per cent, of HIV
      infection among the sample of intravenous heroin abusers were observed in a few
      countries with a high prevalence of intravenous injecting, such as India (in the
      State of Manipur), Myanmar and Thailand. The rest had either few reported cases
      or none at all, even though needle-sharing was found to be common. Great caution
      should be exercised in interpreting prevalence because of vast differences in
      methods of assessment. Given the vulnerability of intravenous drug abusers to
      rapid transmission of HIV infection, the prevention of drug injecting is of
      paramount importance in arresting the spread of the epidemic. Efforts to contain
      drug abuse, though difficult, are a principal means of achieving that end.

PMID- 8305909
TI  - Rapid spread of HIV among injecting drug users in north-eastern states of India.
AB  - Manipur, a north-eastern state of India bordering Myanmar, has experienced very
      rapid transmission of the human immunodeficiency virus (HIV) among its vast drug
      injecting population. Seroprevalence among intravenous drug users increased from
      0 per cent in September 1989 to 50 per cent within six months. With a minimum
      injecting population of 15,000 and seropositivity of over 50 per cent, the
      infection quickly spread to the population at large. One per cent of antenatal
      mothers tested seropositive by 1991. Forming part of the area of South-East Asia
      known as the Golden Triangle, and producing opium and its derivatives, Myanmar
      shares a long international border with four States of the region, and
      populations with a common language and culture move freely across borders. Two
      other north-eastern states of India bordering Myanmar have faced a similar
      epidemic within a short period of time. As a result of serosurveillance for HIV
      since 1986, the epidemic could be detected at an early stage. The present paper
      provides an account of the results of ongoing comprehensive studies conducted in
      the north-eastern states of India on drug-related HIV infection, already a
      serious problem, but possibly still restricted to that region of the country. The
      prevalence of intravenous drug users, their HIV serological status, the
      demographic profile, risk behaviour, the spread of the infection to other groups
      and the problems of harm minimization are also covered.

PMID- 8305910
TI  - Exercise, oxidative stress, and antioxidants: a review.
AB  - Elemental and gaseous oxygen presents a conundrum in that it is simultaneously
      essential for and potentially destructive to human life. Traditionally the
      ability to consume large volumes of oxygen has been assumed to be totally
      beneficial to the organism. In the past 10 years it has become clear that oxygen
      radicals are generated even during normal resting metabolism. Nevertheless, such
      radicals are usually of no appreciable threat since a wide array of protective
      biochemical systems exist. However, under certain circumstances aerobic exercise
      may increase free radical production to a level that overwhelms those defenses. A
      broad array of nutrients such as vitamin C, vitamin E, beta-carotene, and so
      forth are known to suppress such radical events. This paper reviews the status of
      our knowledge relative to the potential benefits of nutritional modification in
      augmenting the organism's normal defense against harmful radical chemistry.

PMID- 8305911
TI  - Effects of varying levels of hypohydration on ratings of perceived exertion.
AB  - To investigate the effects of varying levels of hypohydration on ratings of
      perceived exertion (RPE) during moderate and heavy submaximal exercise, and at
      the lactate threshold (LT) and ventilatory threshold (VT), 9 male subjects cycled
      under states of euhydration (EU), moderate hypohydration (MH), and severe
      hypohydration (SH). The desired level of hypohydration was achieved over a 36-hr
      period by having subjects cycle at 50% VO2max in a 38 degrees C environment on
      two occasions while controlling fluid intake and diet. During submaximal
      exercise, oxygen uptake, ventilation, heart rate, blood lactate, and RPE were not
      significantly different among treatments. Hypohydration did not significantly
      alter LT or VT, or perceptual responses at LT or VT. It is concluded that
      hypohydration of up to 5.6% caused by fluid manipulation and exercise in the heat
      over a 36-hr period does not alter RPE or the lactate or ventilatory threshold,
      nor RPE at the lactate and ventilatory thresholds measured during moderate and
      heavy submaximal cycling in a neutral (22 degrees C) environment.

PMID- 8305912
TI  - Iron status in women aerobic dance instructors.
AB  - This investigation evaluated the iron and nutritional status of 12 highly trained
      aerobic dance instructors who did not take iron supplements (ANS) and 8 who did
      (AS). A control group (C) consisted of 10 age matched controls. The aerobic
      instructors had exercised for approximately 3.8 days/wk, 56 min/session for the
      past 7 yrs. There were no significant differences among groups for energy intake,
      carbohydrate, protein, fat, nonheme iron, heme iron, or total iron intake
      (excluding supplemental iron). But both exercise groups had lower ferritin values
      than the control group. There was also a significant difference in mean cell
      volume (MCV), with both exercise groups having greater values than the control
      group. There were no differences among groups for serum iron, total iron binding
      capacity, transferrin saturation, hematocrit, or hemoglobin. One in three aerobic
      dance instructors had serum ferritin values below 12 micrograms.L-1. Results
      indicate that women exercise leaders have iron profiles that are similar to other
      groups of female athletes. The increased MCV values suggest runners' macrocytosis
      or an exercise induced macrocytosis.

PMID- 8305913
TI  - Metabolic responses when different forms of carbohydrate energy are consumed
      during cycling.
AB  - This study examined the effects of consuming the same amount of carbohydrate in
      solid form, liquid form, or both on metabolic responses during 2 hrs of cycling
      at 70% peak VO2 and on cycling time-trial performance. Subjects consumed 0.4 g
      carbohydrate/kg body mass before and every 30 min during exercise. The liquid was
      a 7% carbohydrate-electrolyte beverage and the solid was a sports bar (1171 kJ)
      in which 76%, 18%, and 6% of total energy was derived from carbohydrate, fat, and
      protein, respectively. Blood obtained at baseline, before exercise, and every 30
      min was analyzed for glucose, insulin, lactate, hemoglobin, hematocrit, and
      plasma volume. There were no differences among the treatments for the blood
      parameters. Total carbohydrate oxidation and time-trial performance were also
      similar among treatments. Under thermoneutral conditions with equal liquid
      ingestion, the metabolic and performance responses are similar when consuming
      carbohydrate as a liquid, solid, or in combination during prolonged, moderate
      intensity cycling.

PMID- 8305914
TI  - Effect of carbohydrate composition on fluid balance, gastric emptying, and
      exercise performance.
AB  - This study examined the effects of serial feedings of different carbohydrate
      (CHO) solutions on plasma volume, gastric emptying (GE), and performance during
      prolonged cycling exercise. Solutions containing 6 g% glucose-sucrose (CHO-6GS),
      8.3 g% high fructose corn syrup (CHO-8HF), 6.3 g% high fructose corn syrup + 2 g%
      glucose polymer (CHO-8HP), and a water placebo (WP) were compared. Ten trained
      male cyclists performed four cycling trials consisting of 105 min at 70% VO2max
      followed by a 15-min all-out, self-paced performance ride. Every 15 min the men
      consumed one of the four test solutions. Blood samples were taken before, during,
      and after exercise to determine blood glucose and plasma volume changes. There
      were no significant differences in performance, GE, or plasma volume changes
      between trials. Blood glucose was significantly elevated at the 105-min time
      point in all CHO trials when compared to WP. The CHO-8HF and CHO-8HP drinks
      resulted in a significantly higher delivery of CHO to the intestine. Higher rates
      of CHO oxidation during the steady-state ride were observed only with the CHO-6GS
      drink.

PMID- 8305915
TI  - Carbohydrate ingestion during exercise: effects on muscle glycogen resynthesis
      after exercise.
AB  - To determine the effect of carbohydrate feeding on muscle glycogen resynthesis, 8
      male cyclists pedaled for 2 hrs on a cycle ergometer at 70% of VO2max while
      consuming either a 10% carbohydrate solution (CHO) or a nonnutritive sweet
      placebo (No CHO). Muscle biopsies were obtained from the vastus lateralis prior
      to, immediately postexercise, and at 2, 4, and 24 hrs of recovery. Blood samples
      were taken before and at the end of exercise, and at specified times during
      recovery. During both trials food intake was withheld for the first 2 hrs of
      recovery, but at 2 hrs postexercise a 24% carbohydrate solution was ingested. The
      rate of muscle glycogen resynthesis during the first 2 hrs of recovery was
      similar for the CHO and No CHO trials. Following ingestion of the 24%
      carbohydrate supplement, the rates of muscle glycogen resynthesis increased
      similarly in both trials. These similar rates of resynthesis following ingestion
      of the carbohydrate supplement were obtained despite significantly greater serum
      glucose and insulin levels during the No CHO trial. The results indicate that the
      carbohydrate feedings taken during exercise had little effect on postexercise
      muscle glycogen resynthesis.

PMID- 8305916
TI  - Nutrient intake of female elite athletes suffering from eating disorders.
AB  - This study assessed the nutrient intake and eating behavior in Norwegian female
      elite athletes suffering from eating disorders (ED) who met the criteria for
      anorexia nervosa (AN), anorexia athletica (AA), or bulimia nervosa (BN). The
      subjects included 7 AN, 43 AA, 42 BN, and 30 controls. Three-day and 24-hr food
      records were used to assess energy and nutrient intake. Results revealed that a
      significant number of AN and AA athletes have diets too low in energy and
      nutrients, the mean intake for energy and CHO being lower than recommended for
      active females. A significant number did not reach the protein level recommended
      for athletes. In addition, there were low intakes of several micronutrients, most
      notably calcium, vitamin D, and iron. The energy and nutritional inadequacy,
      combined with the use of purging, are of major concern since the athletes in this
      study were relatively young. It is unknown whether the abnormal eating pattern is
      a consequence of ED or is typical of top level athletes.

PMID- 8305917
TI  - Postprandial glycemic response in three male endurance athletes.
AB  - The determination of blood glucose response to various carbohydrate foods may
      help athletes in their choice of preexercise feedings. This case study documented
      the postprandial glycemic responses of three male endurance athletes at rest
      after ingestion of 50-gram portions of three carbohydrate foods: graham crackers,
      orange juice, and oatmeal. Plasma glucose response differed in each subject for
      each test food. Two of the three subjects exhibited similar glycemic responses,
      but not to the same test food. Future studies will clarify the relationship
      between carbohydrate ingestion and postprandial glucose response.

PMID- 8305918
TI  - How to help the athlete with bulimia: practical tips and a case study.
AB  - Surveys suggest that 8 to 41% of athletes may struggle with binge/purge and
      bulimic eating behaviors. Many of these athletes with bulimia struggle alone,
      receiving no professional help for recovery. This article offers effective
      counseling strategies for nutrition professionals who want to help bulimic
      athletes. Through a case study of a triathlete who binges, and then purges
      through compulsive exercise, a nutrition care plan is discussed that addresses
      the food and weight concerns commonly expressed by athletes with bulimia. The
      priorities of the care plan are to reduce preoccupation with weight, establish a
      pattern of regular eating, and address the underlying causes of the binges. The
      case demonstrates that nutrition counseling is only one part of the treatment
      program, and emphasizes the importance of developing a team of health
      professionals to assist athletes with bulimia.

PMID- 8305919
TI  - Antiphospholipid antibodies, beta 2-glycoprotein I and thrombosis.

PMID- 8305920
TI  - Mouse models for the antiphospholipid syndrome.

PMID- 8305921
TI  - Congenital complete heart block.

PMID- 8305922
TI  - Elevated levels of the 70 kD heat shock protein in patients with systemic lupus
      erythematosus are not dependent on enhanced transcription of the hsp70 gene.
AB  - The level of the heat inducible hsp70 protein (hsp72) has been shown to be
      elevated in the peripheral blood mononuclear cells of a subset of SLE patients.
      We show that this increased level of hsp70 is not dependent on enhanced
      transcription of the hsp70 gene or elevated levels of the hsp70 mRNA, neither of
      which are observed in SLE patients with enhanced protein levels. This indicates
      that posttranscriptional processes involving either improved translatability of
      the hsp70 mRNA or increased protein stability are responsible for the observed
      increase in protein levels in these patients.

PMID- 8305923
TI  - Systemic lupus erythematosus in Greece. Clinical features, evolution and outcome:
      a descriptive analysis of 292 patients.
AB  - The purpose of this study was the descriptive analysis of patients with systemic
      lupus erythematosus (SLE) with a particular focus on initial clinical features,
      evolution and outcome of disease, prevalence of clinical and serological
      manifestations and identification of clinicoserological associations indicative
      of renal and CNS involvement. The methodology applied was the following:
      retrospective analysis of the clinical charts of 292 unselected patients (246
      female (84.2%) and 46 male (15.7%)) with SLE examined between 1982 and 1992.
      Multivariate analysis and hierarchical log linear models were used to examine for
      clinicoserological associations. Descriptive analysis was based on the prevalence
      of main clinicoserological features and disease outcome. The outcome was examined
      on the basis of the number of flares, the presence of chronic renal failure, the
      presence of central nervous system (CNS) involvement with subsequent disability
      and deaths. Flares were considered the severe alterations in disease status,
      requiring additional therapy to be controlled. The disease begins most frequently
      in the second and third decade of life with cutaneous and joint manifestations,
      while renal and CNS involvement developed later. The prevalence of serious renal,
      pulmonary and CNS involvement as well as the prevalence of RF, anti-Sm and anti
      nRNP antibodies remain low. Multivariate analysis revealed the associations of
      renal involvement with leukopenia and serositis, of anti-Sm with leukopenia, of
      secondary Sjogren's syndrome with RF and of thromboembolic events with
      anticardiolipin antibodies. Patients with childhood onset SLE have a higher
      tendency for developing renal involvement than adult onset SLE patients. In
      addition, anti-Ro(SSA) antibodies were associated with anti-La(SSB) and RF, while
      anti-Sm antibodies were associated with anti-nRNP and RF. Flares occurred with a
      frequency of 0.07 per patient per year. Only 63.6% of flares were accompanied by
      positive anti-dsDNA reactivities. Reported deaths were 0.0047 per patient per
      year. Hierarchical log linear models indicated that the main variables of the
      disease were sufficient to describe our disease model and that the order of the
      interaction between the variables was insignificant. We conclude that the
      prevalence of various clinical features associated with SLE is similar, although
      the prevalence of CNS and pulmonary involvement as well as anti-Sm and anti-nRNP
      antibodies are less prominent in Greek SLE patients than that reported in the
      literature. The various clinicoserological associations detected do not appear to
      be of major significance as they are not powerful enough to subgroup the disease.

PMID- 8305924
TI  - Major histocompatibility complex genes and susceptibility to systemic lupus
      erythematosus in northern India.
AB  - Fifty-eight patients with systemic lupus erythematosus (SLE) from Northern India
      were tissue typed for HLA class I and II antigens. The results revealed an
      appreciable increase of HLA-DR4 (37.5%) among patients compared with controls
      (17.9%), P < 0.03. Additionally, haplotype B8-DR3 was encountered frequently in
      the patient group. The findings suggest an important role of MHC genes in
      influencing susceptibility to SLE.

PMID- 8305925
TI  - Systemic lupus erythematosus: sex hormones in male patients.
AB  - Systemic lupus erythematosus (SLE) is a rare disease in males. There is evidence
      that a functional state of hypoandrogenism is important in the pathogenesis of
      the disease. We analysed the levels of several hormones (follicle stimulating
      hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2), free
      estradiol (FE2) and prolactin (PRL)) in 17 male SLE patients and 17 male healthy
      controls with similar age distribution. Three lupus patients were excluded from
      the analysis due to previous cyclophosphamide therapy or pre-puberty. Thus 14
      male lupus patients were eligible for the study. Six of the 14 SLE patients (43%)
      showed at least one abnormal level of FSH, LH or T. There were no abnormalities
      in these hormones in the 17 controls. This difference was significant (P < 0.01).
      In five of these 6 male patients (36% of all lupus patients) the hormonal profile
      was compatible with a functional state of hypoandrogenism (high LH and/or low T).
      The ratio E2/T (estradiol/testosterone:pmol/nmol) was also significantly higher
      in the SLE group (average = 6.5; SD 4.3) when compared with that of the control
      group (average 4.2; SD 1.2; Mann-Whitney rank sum test: P < 0.03). There were no
      significant differences in E2, FE2 or PRL between lupus patients and controls. We
      did not confirm the notion that left-handedness is frequent in male lupus as all
      our patients were right-handed. We found a significantly higher prevalence of sex
      hormone abnormalities in male lupus patients when compared with healthy controls
      with a similar age distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8305926
TI  - Fish oil derivatives as a prophylaxis of recurrent miscarriage associated with
      antiphospholipid antibodies (APL): a pilot study.
AB  - Since 1989, 22 patients with persistent antiphospholipid syndrome (PAPS)
      associated with recurrent miscarriage (defined as three or more miscarriages)
      were treated with fish oil, equivalent to 5.1 g eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) at a ratio of 1.5 EPA to DHA. Twenty-two patients had
      23 pregnancies (one patient had two pregnancies) over a period of 3 years. There
      was only one intrauterine fetal death at the 27th week associated with pre
      eclampsia. Twenty-one pregnancies, 19 of which ended after the 37th week,
      produced a baby. Two pregnancies ended with cesarean section for pre-eclampsia at
      30th and 35th week of gestation and one is ongoing at 32nd week. All babies are
      well. The weight at birth of babies delivered at term was always > 2500 g. These
      encouraging results favour a therapeutic role, without any adverse reaction, of
      fish oil to prevent recurrent miscarriage in PAPS.

PMID- 8305927
TI  - Prevalence of the type I complement C2 deficiency gene in Swedish systemic lupus
      erythematosus patients.
AB  - The prevalence of type I complement C2 deficiency in Swedish systemic lupus
      erythematosus (SLE) patients was investigated by DNA analysis. The characteristic
      28 base pair deletion was determined by polymerase chain reaction analysis
      followed by gel electrophoresis. Five of the 86 patients (5.8%) retrieved from a
      defined population of 160,000 individuals were heterozygous for the C2Q0 gene
      compared with one heterozygote of 100 local blood donors (1%), the difference in
      prevalence not being significant. Among 26 other SLE patients, two patients who
      are siblings were C2Q0 homozygous. No distinctive clinical features among the
      patients with C2Q0 genes were obvious, although none had renal involvement.

PMID- 8305929
TI  - Neonatal lupus liver disease.
AB  - Neonatal lupus erythematosus (NLE) is an autoimmune disease characterized by
      complete congenital heart block and/or transient skin lesions of subacute
      cutaneous lupus erythematosus. We report that in approximately 10% of cases of
      NLE with heart block or skin disease, liver disease also occurs (4 of 35 cases in
      our series). Cholestasis was the major feature in our cases. Although the
      cholestasis may be severe, the disease process appears to be transient and
      surviving babies have been healthy on follow-up. In one liver examined for
      antibody deposition, IgG antibody deposits, presumably of maternal origin, were
      present. Three maternal sera were examined for autoantibodies, including liver
      specific autoantibodies. No liver-specific autoantibodies were found. Rather, the
      maternal autoantibodies too were the ubiquitous Ro/SSA-associated autoantigens.
      The autoantibodies bound the 60 kDa SSA/Ro ribonuclear protein (three of three
      sera), the 52 kDa SSA/Ro protein (two of three sera) and the SSB/La ribonuclear
      protein (two of three sera).

PMID- 8305928
TI  - Psychiatric disorder in Malaysians with systemic lupus erythematosus.
AB  - All 79 patients who attended a University Systemic Lupus Erythematosus (SLE)
      Clinic over a 6 month period were assessed using the Clinical Interview Schedule
      for psychiatric disorder. Using the ICD-9 Classification, 40 were found to have
      psychiatric disorder, 26 having depressive neurosis, six anxiety neurosis, five
      endogenous depression and three dementia. The group with psychiatric disorder had
      significantly poor family support as well as lack of a confidant compared to the
      group without psychiatric disorder (P < 0.01). There was no difference between
      the group with psychiatric disorder and those without psychiatric disorder in
      terms of age, duration of illness, ethnicity and severity of SLE. Psychiatric
      disorder is common affecting more than half the subjects and depression was the
      most frequent diagnosis.

PMID- 8305930
TI  - 1982 revised criteria for classification of systemic lupus erythematosus--ten
      years later.

PMID- 8305931
TI  - [The value of MRI in ruptures of the corpus cavernosum].
AB  - MRI has only recently been described in the evaluation of traumatic rupture of
      the corpora cavernosa. Our case report emphasises the perfect correlation between
      the MRI findings and the anatomical lesion. This examination therefore
      constitutes a valuable aid in the pretreatment assessment of rupture of the
      corpora cavernosa.

PMID- 8305932
TI  - [Diagnosis of ectopic ureteral openings in the seminal tract. Value of modern
      imaging].
AB  - We recently observed 3 cases of ectopic ureteric orifice in the seminal tract in
      patients between the ages of 16 and 42 years. The first case was discovered
      incidentally, but the other two presented with scrotal symptoms. Intravenous
      urography, ultrasonography and computed tomography contributed to the diagnosis,
      but magnetic resonance imaging was the most conclusive, avoiding the need for
      deferentography in one case. These 3 recent cases allow an evaluation of the
      respective value of these various imaging modalities.

PMID- 8305933
TI  - [Carcinoma in situ on ureteric stump after cystectomy treated by BCG].
AB  - Intravesical BCG is the reference adjuvant therapy for superficial urothelial
      tumours. Its adverse effects and the modalities of follow-up are now clearly
      established. We treated a female patient by antegrade BCG instillation for a
      carcinoma in situ discovered in a ureteric stump following cystectomy for
      generalised CIS. Treatment was well tolerated and no recurrence was observed with
      a follow-up of 3 years.

PMID- 8305934
TI  - [Georges N Papanicolaou. (1883-1962) and major advances in urinary cytology].

PMID- 8305935
TI  - [Urinary lithiasis and pregnancy].
AB  - The incidence of renal stones in pregnant women is 1 in 1500. The diagnosis may
      be made more difficult by the particular anatomo-physiological conditions of
      pregnancy. Ultrasonography is not always sufficient to localise the stone and can
      be completed by intravenous urography, which is not contraindicated in pregnant
      women. In more than one half of cases, the stones are eliminated spontaneously
      during conservative treatment. The urologist may need to intervene in the case of
      complicated stones: internal or external urinary diversion is generally
      sufficient to palliate the problem until term. As extracorporeal lithotripsy is
      contraindicated in pregnant women, some authors recommend ureteroscopy or
      percutaneous nephrolithotomy when radical treatment is required. Surgical
      treatment is very rarely indicated.

PMID- 8305936
TI  - [Fragmentation of urinary calculi using the Lithoclast EMS. Technique and
      results].
AB  - The Lithoclast is an endoscopic lithotriptor which uses the ballistic energy
      produced by a small hand-held apparatus, by the movement of a small metal part
      (the projectile) driven by a jet of compressed air. The energy is transmitted to
      a metal rod whose diameter is selected according to the application: 0.8 or 1 mm
      in the ureter; 2 mm in the bladder and kidney. We have used this apparatus to
      treat 40 stones in 39 patients (25 ureteric stones, 11 renal stones, 4 bladder
      stones). Satisfactory fragmentation was obtained for 39 of the 40 stones (97.5%).
      The apparatus is very easy to use in the kidney and bladder (the risk of urinary
      tract perforation is very low at this level). The risk of perforation of the
      ureteric wall by 0.8 mm or 1 mm rods is considerable (12% of cases), but these
      punctate lesions heal rapidly over a double J stent. Special techniques should be
      used in the ureter to limit the risk of pushing the stone towards the renal
      pelvis.

PMID- 8305937
TI  - [Percutaneous nephrolithotomy after failure of extracorporeal shockwave
      lithotripsy. Indications, results, perspectives].
AB  - Eighty-one of the 579 extracorporeal lithotripsies (ECL) performed between 1987
      and 1992 with an ultrasound-guided hydroelectric lithotriptor required the use of
      another treatment modality. 53 percutaneous nephrolithotomies (PCNL) were
      performed in these 81 patients after failure of ECL (21 for non-fragmentation, 32
      for residual fragments). The authors analyse the factors responsible for failure
      in order to select the more appropriate type of treatment for different types of
      stones. The site of the stones, their size, their radiographic appearance, their
      chemical composition, the number of ECL sessions and the number of days spent in
      hospital were compared between the PCNL and ECL groups. Smooth, homogeneous
      stones denser than bone and larger than 15 mm in diameter were significantly more
      resistant to ECL, despite an increased number of shock waves. PCNL was successful
      in 92% of cases of non-fragmented stones (with no residual fragments). The
      success rate for multiple residual fragments was 64%. In view of the risk of
      complications associated with residual fragments, regardless of their size, the
      potential risks of ECL and cost imperatives, the authors recommend that these
      stones, considered to be resistant, should be treated immediately by PCNL, as the
      results of PCNL after ECL are less satisfactory.

PMID- 8305938
TI  - [Treatment of intradiverticular lithiasis by percutaneous methods (19 caliceal
      diverticuli)].
AB  - The main technical procedures in percutaneous nephrolithotomy are the direct
      puncture of the diverticulum (precise puncture may be required to place the tract
      directly on to the stone), and treatment duration the diverticulum could be
      coagulated and a large nephrostomy catheter could be left in place two days. No
      complication was encountered. One patient refused the treatment after
      unsuccessful puncture. The nephrostomy tube was left open for two days of
      drainage. Mean hospital stay was 5 days. Three patients required E.S.W.L because
      of persistent symptoms. One month after treatment 13 of 18 patients intravenous
      urography showed obliteration of the diverticulum (72%); Three months after 84%
      (15/18) of our patients were stone free and 94% (17/18) symptom free.
      Percutaneous nephrolithotomy should be performed for symptomatic patients, it has
      low complication rate and should be reserved for patients with persistent
      symptoms after E.S.W.L.

PMID- 8305939
TI  - [The scintigraphic effect of extracorporeal lithotripsy: prospective series of 25
      cases].
AB  - 25 patients with non complicated renal stones were treated by extracorporeal
      shockwave lithotripsy (ESWL) using Sonolith 3000 an electrohydraulic generator
      type. They were evaluated before, 15 days and 3 months after ESWL by renal
      scintigraphy, using for 15 of them technetium -99m dimer captosuccinic acid and
      technetium -99m-diethylene-triamine acetate for the last 10. This follow up
      scintigraphic study shows no reduction of glomerular filtration rate after ESWL
      but some focal parenchymal lesions. Very few of these lesions persist at 3
      months. These parenchymal damages seem to be less frequent and less persistent
      than with piezo-electric lithotripter.

PMID- 8305940
TI  - [Treatment of sexual impotency by intra-cavernous injections of prostaglandin E1.
      Report of 180 patients].
AB  - As already reported, PGE1 induces a valid erection, when administered
      intracavernously, without causing prolonged erection or general side effects. We
      have tested PGE1 (< 20 micrograms) in 180 patients suffering from organic
      erectile impotence, a complete erection was observed in 130 (72.2%), while
      incomplete erection was noted in 37 (20.5%). In both groups (92.7%) erection was
      sufficient for sexual intercourse. Among the best results, 41 patients had
      previously received high doses intracavernous injection of papaverine, without
      any benefit, and 15 patients have cavernosal venous leakage documented by
      cavernosometry and cavernosography before prostaglandin E1 test. Tumescence
      without rigidity was noted in 13 (7.2%). Of these 167 patients, 95 entered an
      autoinjection protocol for treatment of erectile dysfunction, using special
      device. In our series neither systemic reaction nor prolonged erection occurred.
      No fibrosis of cavernous tissue or scar formation was observed after up to 125
      injections. However, 19 patients (10.5%) reported burning sensations during the
      entire period of erection and one patient (0.5%) had an haematoma at the site of
      the injection. PGE1 is effective in inducing artificial penile erection and it
      has a role in the diagnosis and treatment of erectile dysfunction, it is
      considered to be a more suitable agent than other vasoactive drugs.

PMID- 8305941
TI  - [Tumors of the superior urinary tract and associated bladder tumors: clinical and
      etiological aspects].
AB  - In a series of 107 patients treated over an 11-year period for upper urinary
      tract tumours (UTT), 30 had a synchronous or metachronous associated bladder
      tumour. The bladder tumour preceded the UTT in 10.3% of cases, the bladder tumour
      was synchronous in 6.5% of cases and the bladder tumour occurred after the UTT in
      15% of cases, the incidence of UTT after cystectomy over this 11-year period was
      3.3%. The median time to recurrence of the UTT after bladder tumour was 17
      months. The median time to recurrence of the bladder tumour after the UTT was 12
      months. The risk of bladder recurrence after treatment of the upper tract tumour
      was studied in relation to site, type of treatment, multifocal nature, stage and
      grade of the UTT and the presence of a previous or synchronous associated bladder
      tumour. None of these parameters constituted a predictive factor of bladder
      recurrence after treatment of an upper tract tumour. Comparison of survival
      between the UTT + bladder tumour group and the UTT alone group did not reveal any
      significant difference (p = 0.10). The theory of cellular implantation
      facilitated by vesicorenal reflux and the multifocal theory are complementary
      explanations of the multifocal and recurrent nature of urothelial tumours.

PMID- 8305942
TI  - [Intravesical instillations of BCG and bladder carcinoma in situ].
AB  - 32 patients with bladder carcinoma in situ (CIS) were treated by intravesical
      instillations of BCG immun F Pasteur between 1988 and 1991. The CIS was isolated
      (13 cases, 40.6%) or associated with a pTa papillary tumour (10 cases, 31.2%),
      pT1 tumour (8 cases, 25.1%) or pT2 tumour (1 case, 3.1%). The protocol consisted
      of a series of weekly instillations of 150 mg of BCG for 6 weeks, repeated once
      in the case of persistent lesions on the first endoscopic follow-up examination.
      Patients were reviewed in the outpatients department every 3 months for 1 year,
      then every 6 months for 2 years in the absence of recurrence. Follow-up consisted
      of clinical examination, urine cytology and histology. The overall success rate,
      defined by complete resolution of the cytological and histological lesions for
      the total population was 81.25% (25/32) with a mean follow-up of 22.5 months.
      18.75% (6/32) of cases were considered to be failures. Complications of treatment
      were observed in 59% of patients, but only required discontinuation of
      instillations in five patients (15.6%). In conclusion, intravesical BCG is the
      treatment of choice of bladder carcinoma in situ in the absence of detrusor
      invasion and contraindications to BCG.

PMID- 8305944
TI  - Pharmaceutical producer price index hits lowest level in 20 years.

PMID- 8305943
TI  - Reform contenders argue the merits of alliance models.

PMID- 8305945
TI  - Are futile-care policies the answer? Providers struggle with decisions for
      patients near the end of life.
AB  - Clinicians and ethicists are working to develop effective guidelines on futile
      care, but even reaching for definitions presents daunting challenges. When is
      patient care futile? Who decides? What are the legal, operational and health care
      resource utilization issues involved? An examination of the range of issues. And
      a look at the maturing hospice field.

PMID- 8305946
TI  - Mature hospice field takes its place in the mainstream.

PMID- 8305947
TI  - Coming up to speed. Execs see primary care construction as key to successful
      networks.

PMID- 8305948
TI  - Linking incomes & outcomes.

PMID- 8305949
TI  - Des Moines, Iowa. Providers seek to build statewide delivery systems.

PMID- 8305950
TI  - Illinois Blue Cross and Blue Shield Medical Director Arnold Widen. Interview by
      Jim Montague.

PMID- 8305951
TI  - Hospitals model best practices in medical records management.

PMID- 8305952
TI  - Mission possible: building PHO partnerships that work.

PMID- 8305953
TI  - A shot in the arm for children's health in Atlanta. Interview by Kathryn Taylor.
AB  - Three years ago, Atlanta's Scottish Rite Children's Medical Center began a
      statewide children's immunization program. The success of that program has
      encouraged other community organizations to model themselves after Scottish
      Rite's, including a similar initiative launched by The Atlanta Project (TAP). The
      medical center lent its expertise--and that of senior vice president Judson L.
      Hawk Jr., M.D.--to TAP. Staff Editor Kathryn Taylor recently spoke to Hawk about
      his three-year stint as senior adviser for children's issues at TAP, and his role
      in developing an immunization program for the Atlanta area.

PMID- 8305954
TI  - Moving forward to shape the debate.

PMID- 8305955
TI  - A physical chemical approach to the analysis of acid-base balance in the clinical
      setting.
AB  - We evaluated the clinical application of a model of acid-base balance, which is
      based on quantitative physical chemical principles (Stewart model). This model
      postulates that acid-base balance is normally determined by the difference in
      concentration between strong cations and anions (strong ion difference [SID]),
      PCO2, and weak acids (primarily proteins). We measured electrolytes and blood
      gases in arterial blood samples from 21 patients in a medical or surgical
      intensive care unit or emergency room of a tertiary care hospital. The measured
      SID frequently differed from SID calculated from the measured blood components,
      which indicates that unmeasured cations or anions are present; these could not be
      accounted for by lactate, ketones, or other readily identifiable ions. We used an
      approach to acid-base analysis that is based on changes in base excess or deficit
      due to changes in: (1) free water as assessed by [Na+]; (2) in [Cl-]; (3) protein
      concentration; and (4) "other species" (ie, anion and cations other than [Na+],
      [K+], and [Cl-]). The contribution of "other species" was obtained from the
      difference between the SID measured and that predicted from Stewart's equation.
      It could also be calculated from the difference between the standard Siggaard
      Anderson calculation of base excess and base excess attributable to free water,
      [Cl-], and proteins (ie, base-excess gap). Our results indicate that the SID gap,
      base excess gap, and anion gap reflect the presence of unmeasured ions, and both
      the anion-gap and base-excess gap provide readily available estimates of the SID
      gap. This provides a simple bedside approach for using the Stewart model to
      analyze the nonrespiratory component of clinical acid-base disorders and
      indicates that, in addition to unmeasured anions, unmeasured cations can be
      present.

PMID- 8305956
TI  - Effect of pretreatment with anticonvulsants on theophylline-induced seizures in
      the rat.
AB  - Seizures, often with fatal outcome, are a manifestation of pronounced
      theophylline toxicity. Prodromal symptoms are not always apparent, and the
      seizures are reported to be, in certain cases, refractory to treatment with
      anticonvulsant drugs. The purpose of this investigation was to examine, by an
      established animal model, which of the commonly used anticonvulsants can reduce
      the central nervous system sensitivity to theophylline neurotoxicity and what
      should be the preferred treatment in cases in which theophylline toxicity is
      anticipated. The anticonvulsant agents in doses that are found to be effective in
      other types of experimentally induced seizures in rats, clonazepam 5 mg/kg,
      diazepam 5 mg/kg, phenytoin 8 mg/kg, phenobarbital 100 mg/kg, valproic acid 150
      mg/kg, and magnesium sulphate 300 mg/kg, or the vehicle (controls) were
      administered intravenously to Lewis female rats. Thirty minutes later,
      theophylline was infused at a constant rate of 1.3 mg/min until onset of maximal
      seizures. Theophylline concentrations in the cerebrospinal fluid, brain, and
      serum were assayed by a high-performance liquid chromatography method. It was
      found that pretreatment with either clonazepam, diazepam, phenobarbital, or
      valproic acid increased the central nervous system thresholds to the theophylline
      induced seizures, whereas phenytoin and magnesium sulphate did not attenuate the
      sensitivity of the brain to the stimulatory action of this widely used
      bronchodilator. Therefore, whenever theophylline toxicity is suspected, treatment
      with either diazepam, clonazepam, phenobarbital, or valproic acid can reduce the
      hazard associated with theophylline-induced seizures.

PMID- 8305957
TI  - Absence of supply dependence of oxygen consumption in patients with septic shock.
AB  - We tested whether oxygen consumption (VO2) was dependent on oxygen delivery (QO2)
      in 10 patients with septic shock when QO2 was changed by the use of the inotropic
      agent, dobutamine. The mean acute physiology and chronic health evaluation
      (APACHE) II score of the patients was 27.3 +/- 8.1 with a mean blood pressure on
      entry of 66.8 +/- 12.4 mm Hg, and all had been volume resuscitated to a pulmonary
      artery occlusion pressure of greater than 10 mm Hg. We measured VO2 by analysis
      of respiratory gases (VO2G) while calculating VO2 by the Fick equation (VO2F) at
      three different O2 deliveries. When the dobutamine infusion rate was increased
      from 2.5 +/- 4.0 to 12.3 +/- 6.0 micrograms/kg/min, thermodilution cardiac output
      increased from 7.7 +/- 2.6 to 10.1 +/- 2.7 L/min (P < .01). Accordingly,
      dobutamine increased QO2 from 13.5 +/- 3.8 to 18.2 +/- 4.3 mL/min per kg
      (increase of 36.4% +/- 19.7%; P < .01), but VO2G did not increase (3.2 +/- 0.5 to
      3.2 +/- 0.6 mL/min per kg). During these same interventions, the VO2F tended to
      increase (2.9 +/- 0.7 to 3.4 +/- 0.8 mL/min per kg, P < .06), presumably a
      spurious correlation because of measurement errors shared by the calculation of
      VO2F and QO2. Neither lactic acidosis nor acute respiratory distress syndrome
      (ARDS) conferred supply dependence of VO2G, but the presence of ARDS was
      predictive of death in this cohort. It is concluded that VO2 is independent of
      QO2 in patients with septic shock and lactic acidosis. These data confirm that
      maximizing QO2 beyond values achieved by initial fluid and vasoactive drug
      resuscitation of septic shock does not improve tissue oxygenation as determined
      by respiratory gas measurement of VO2.

PMID- 8305958
TI  - Safety and efficacy of intravenous immunoglobulin prophylaxis in pediatric head
      trauma patients: a double-blind controlled trial.
AB  - Infection is one of the major complications of severe head trauma in children. To
      assess whether intravenous immunoglobulin (IVIg) decreases the incidence of
      secondary infection after head injury in children, a randomized, double-blind
      trial was performed. Thirty-three children (mean age, 6.67 years; mean injury
      severity score, 32.8; mean Glasgow coma score, 6.1) with severe head injuries
      were enrolled; 1 child was excluded, 18 received IVIg, and 14 received the
      placebo preparation. Four hundred milligrams per kilogram of IVIg or albumin
      placebo was administered within 48 hours of admission. IgG levels were obtained
      before the infusion and then 1 week later. Patients were monitored for evidence
      of infection for the next 21 days. There was a 66% increase in mean IgG levels in
      the treatment group compared with 45% in the control group (P = .057). One death
      occurred in the IVIg group and two in the placebo group. No significant
      differences in the incidence of pneumonia, sepsis, presumed sepsis, or any other
      type of infection was noted. There was no difference in the number of days on
      mechanical ventilation or in number of hospital days. There were no side effects.
      It is concluded that prophylactic administration of commercial IVIg at a dose of
      400 mg/kg, although safe, had no effect on the incidence of secondary infections
      in children with severe head injuries.

PMID- 8305959
TI  - The relationship between the arteriovenous carbon dioxide gradient and cardiac
      index.
AB  - It has been reported that under normal conditions, mixed venous blood gases have
      approximated arterial samples; however, during cardiac arrest or severe
      cardiogenic shock, marked differences between arterial and venous blood gases
      have been noted. To further assess the relationships between arterial and mixed
      venous blood gases and cardiac index, a study population was chosen consisting of
      patients with less severe states of cardiac impairment. The differences between
      arterial and mixed venous PCO2s and pHs were compared with cardiac indexes (CI)
      of 44 patients in an intensive care unit with arterial lines and Swan-Ganz
      catheters in place. Twenty-six patients with normal CIs (2.6 to 4.1 L/min/m2) had
      a mean difference in mixed venous-arterial PCO2 (delta PCO2) of 4.88 +/- 0.40 mm
      Hg. In patients with low CIs (< 2.6), the delta PCO2 was 7.44 +/- 0.63 mm Hg (P =
      .001). The difference of mixed venous and arterial pH (delta pH) was 0.027 +/-
      0.004 pH units for patients with normal CIs and 0.04 +/- 0.003 pH units for those
      with low CIs (P < .002). When the CIs of all patients were plotted against the
      delta PCO2s, there was an inverse linear relationship wherein delta PCO2
      increased as CI decreased (r = -.47, P = .0011). There is an inverse relationship
      between delta PCO2 and CI that has not been previously described. An elevated
      delta PCO2 may be a marker of a low cardiac index.

PMID- 8305960
TI  - Importance of tonicity of carbicarb on the functional and metabolic responses of
      the acidotic isolated heart.
AB  - In this study, the physiological and metabolic effects of Carbicarb administered
      as an isotonic (150 mmol/L Na[n[]I+) or hypertonic (1 mol/L Na[n[]I+) solution
      over 2 minutes in the acidotic isolated heart were compared. Physiological
      monitoring as well as 31P and 23Na nuclear magnetic resonance spectroscopy were
      performed. Both isotonic and hypertonic Carbicarb induced comparable dose
      dependent increases in intracellular pH as well as decreases in inorganic
      phosphate and increases in creatine phosphate concentrations, which were
      sustained for 20 minutes. However, immediate functional improvement was greater
      in hearts receiving isotonic Carbicarb. Metabolic acidosis conditions resulted in
      a 27% increase in cytosolic sodium by 30 minutes (P < .05). In this setting,
      hypertonic Carbicarb induced a large transient increase in cytosolic sodium,
      whereas isotonic Carbicarb caused immediate and sustained decreases in cytosolic
      sodium. These data suggest that isotonic Carbicarb may have more beneficial
      effects on cardiac function than hypertonic Carbicarb. These effects may be
      related to associated changes in cytosolic sodium.

PMID- 8305961
TI  - What good are we doing? The role of clinical research in enhancing critical care
      medicine.
AB  - The amount of financial and other resources used by physicians in the treatment
      of critically ill patients makes it incumbent upon physicians to ensure that
      sufficient benefit is obtained from these resources and that physicians are in
      fact doing good for their patients. Knowing that one is in fact doing good
      requires an understanding of what counts as benefit. Current medical practice
      suggests that patient benefit is typically understood in terms of physiological
      changes and responses, highlighting the role of medical subspecialties in patient
      care. An alternative view is suggested, which requires a broader understanding by
      physicians of patient needs and welfare. This broader understanding calls for an
      ambitious research agenda so that physicians will be able to learn how they can
      genuinely help critically ill patients and their families during times of
      illness. Carrying out such an agenda requires overcoming the ethical challenges
      of performing research on patients as vulnerable as critically ill patients. It
      also requires physicians to establish collaborative ties with other professionals
      so that truly interdisciplinary research can be performed on a routine basis.

PMID- 8305962
TI  - Peters'-Plus syndrome with agenesis of the corpus callosum: report of a case and
      confirmation of autosomal recessive inheritance.
AB  - We describe a male infant, born to healthy consanguineous parents, with Peters'
      Plus syndrome. The syndrome includes corneal opacification, short stature, cleft
      lip and palate, low set ears, short hands and feet and mental retardation.
      Cranial CT scan showed agenesis of the corpus callosum which has not, to our
      knowledge, previously been described in Peters'-Plus syndrome patients. The
      consanguinity of the parents is in agreement with the proposed autosomal
      recessive inheritance.

PMID- 8305963
TI  - Phenotypic correlations of ocular coloboma without known cause.
AB  - Ocular coloboma can occur as an autosomal dominant condition or as part of a
      known syndrome or chromosomal abnormality. We have designated those patients with
      ocular coloboma who do not fit into any of these three groups as having coloboma
      without known cause. We completed a retrospective review of 58 patients from our
      clinics with coloboma without known cause to determine the frequency of other co
      existing congenital malformations and mental retardation. Mental retardation was
      present in 14 of the 42 patients (33%) who were more than 1 year of age. However,
      only 14% of the children who had no other malformations had mental retardation,
      whereas 57% of those with other malformations were mentally retarded. We found
      that the severity of the colobomatous malformation did not correlate with
      intellect.

PMID- 8305964
TI  - Agenesis of the corpus callosum associated with MASA syndrome.
AB  - MASA syndrome includes mental retardation, adducted thumbs, shuffling gait and
      aphasia or speech delay. MASA syndrome, X-linked hydrocephalus and X-linked
      spastic paraplegia have been linked to the same markers on Xq28 and perhaps
      represent variation in the clinical expression of the same gene or manifestations
      of different mutant alleles. The present family includes five males in two
      generations with borderline to mild mental retardation (5/5), speech delay (5/5),
      spastic paraplegia (5/5), adducted thumbs (2/5) and marked hydrocephalus (1/5).
      Of these males, four were evaluated by MRI or CT scan and all four were
      determined to have partial to complete agenesis of the corpus callosum (ACC). DNA
      studies confirm linkage to Xq28 probe St14 (DXS52) with a lod score of 2.86 and
      no recombination. It is not known if X-linked ACC is linked to the same Xq28
      region.

PMID- 8305965
TI  - Blepharophimosis, ptosis, polythelia and brachydactyly (BPPB): a new autosomal
      dominant syndrome?
AB  - A father and two sons with blepharophimosis, ptosis, polythelia and brachydactyly
      are presented, apparently without other abnormalities. The features do not fit
      into any previously described syndrome. This condition may represent a hitherto
      undescribed syndrome, although resemblance with the blepharophimosis-ptosis
      epicanthus inversus syndrome exists. Inheritance is probably autosomal dominant.

PMID- 8305966
TI  - Familial hydrocephalus with a low-insertion umbilicus.
AB  - Two brothers, age 16 months and 3 years, had a seemingly unique combination of
      hydrocephalus of the lateral ventricles and a low-insertion umbilicus. Both had
      similar mildly unusual facies and inguinal hernias; one had unilateral
      cryptorchidism. The older brother had tetralogy of Fallot, and the younger had
      mildly enlarged, echogenic kidneys with vesicoureteral reflux. Neither boy had
      adducted thumbs, pyramidal tract signs, or significant developmental delay. A
      review of the literature on familial hydrocephalus found no similar cases. A low
      set umbilicus is not a frequently noted anomaly; its embryology and associated
      syndromes are discussed. The association of hydrocephalus and a low-set umbilicus
      appears to be the manifestation of a monogenic disorder in this family, and could
      be inherited in either an autosomal recessive or X-linked recessive manner.

PMID- 8305967
TI  - Craniofrontonasal dysplasia in two male sibs.
AB  - Craniofrontonasal dysplasia (CFND) was diagnosed in a male child who had
      bilateral coronal craniosynostosis, midline facial clefting with cleft lip and
      palate, a broad and high forehead, and hypertelorism. The parents were normal and
      there was no family history suggestive of CFND. A small recurrence risk was
      counselled and prenatal ultrasound was recommended in the next pregnancy. At 23
      weeks, the ultrasound scan detected a number of dysmorphic features and the
      pregnancy was terminated. Autopsy of the aborted male foetus showed the following
      features: High arched palate, a sloping forehead, flattened nose and receding
      chin, multiple joint contractures, particularly of the mid phalangeal joints,
      elbows and ankles. This report highlights the occurrence of CFND in two male
      siblings born to normal parents, and therefore the need to perform prenatal
      ultrasound in a subsequent pregnancy, even if CFND is diagnosed in an isolated
      case.

PMID- 8305968
TI  - An additional case of pachygyria, joint contractures and facial abnormalities.
AB  - Two previous case reports have described an apparently new lethal syndrome
      consisting of pachygyria, joint contractures and facial abnormalities (Winter et
      al., 1989; Tsukahara et al., 1990). Another report describes a non-lethal case in
      which dysmorphic features were not noted (Massa et al., 1988). We now report on
      what appears to be an additional lethal case. This male infant had a lethal
      condition with features of large fontanelle, pachygyria with incomplete
      opercularization, varus contractures of the hands and feet, small palpebral
      fissures, hypertelorism, a small penis, cryptorchidism, camptodactyly and a
      sandal gap deformity. These cases appear to represent a new lethal lissencephaly
      syndrome associated with arthrogryposis and facial dysmorphism, which we propose
      to call the Winter-Tsukahara syndrome.

PMID- 8305969
TI  - Expansion and tumour specific cytokine secretion of bryostatin-activated T-cells
      from cryopreserved axillary lymph nodes of breast cancer patients.
AB  - Current adoptive immunotherapy strategies in cancer patients require large
      numbers of activated T-cells and are limited by the availability of autologous
      tumour. We describe a novel method of T-cell activation that produced relatively
      rapid, high-fold expansion of stored, frozen lymphocytes obtained from the lymph
      nodes of 20 breast cancer patients during axillary dissection but does not
      require autologous tumour. In vitro exposure of thawed cells to bryostatin-1 (B),
      a non-tumour promoting protein kinase C activator and ionomycin (I), a calcium
      ionophore, at day 0 followed by culture in low dose interleukin-2 (IL-2 20 units
      ml-1) and restimulation again on day 10 results in 269-28,206 fold (geometric
      mean = 2254) expansion in cell numbers counted 17 days after initial stimulation.
      Analysis of cell surface markers revealed that B/I expanded human cells were
      predominantly T-cells (83-97%) and consisted of a mixture of CD8+ (46-74%) and
      CD4+ (4-30%) cells. B/I expanded cells did not lyse autologous tumour cells when
      tested in a 4-h 51Cr release assay, but murine studies reported previously have
      demonstrated specific and curative in vivo efficacy in MCA-105 tumour-bearing
      mice despite an inability to lyse autologous tumour in vitro. B/I expanded T
      cells from five of six patients secreted the cytokines tumour necrosis factor
      alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in response to co-culture with
      autologous tumour cells but not with irrelevant tumour. These results are
      analogous to findings in a murine model, in which non-cytolytic B/I expanded T
      cells mediated specific, curative anti-tumour effects in vivo, and lay the
      groundwork for a clinical trial of this novel strategy for the adoptive
      immunotherapy of breast cancer patients.

PMID- 8305970
TI  - Isolation and expansion of lymphocytes from gastrointestinal tumour tissue.
AB  - Adoptive cellular immunotherapy (ACI) with tumour-infiltrating lymphocytes (TIL)
      has met with some success in patients suffering from malignant melanoma. However,
      the success of this approach hinges on the successful isolation and in vitro
      expansion of TIL. Viable, IL-2 responsive TIL were obtained from only two of five
      gastrointestinal primary or 'non-lymph node' secondary gastrointestinal tumours.
      In contrast, proliferating TIL were successfully expanded from four out of five
      lymph node secondary deposits from gastrointestinal cancer patients, but these
      TIL were non-cytolytic. Conversely, proliferating lymphocytes were generated from
      six out of seven malignant effusions from gastrointestinal cancer patients in the
      late phase of their disease. Despite the presence of effective anti-tumour
      cytotoxic activity in one such culture, these lymphocytes failed to proliferate
      sufficiently for potential clinical use. Consequent upon these findings, we are
      sceptical that ACI using mononuclear cells infiltrating primary or secondary
      sites from patients with gastrointestinal cancer will be feasible.

PMID- 8305971
TI  - Mitoxantrone for malignant pleural effusion due to metastatic sarcoma.
AB  - Malignant pleural effusion due to metastatic sarcoma is a difficult problem to
      treat. Mitoxantrone hydrochloride is an anthracenodione that has been reported to
      be useful when used intracavitary for malignant effusion due to gynaecological
      malignancies. We reviewed 15 cases of malignant pleural effusion due to pleural
      involvement by metastatic sarcoma that were treated with intrapleural
      mitoxantrone. None of the patients had previous pleurodesis. A standard dose of
      20 mg per square metre in 50 cc of saline solution was instilled by chest tube
      after drainage of the effusion. All patients were initially evaluated by chest
      CAT scans and chest films, control films were done immediately and 6 weeks after
      treatment. Thirteen cases were evaluated. Three patients presented with fever,
      two patients had local pain and one patient developed neutropenia. Three patients
      did not respond to the treatment. Complete resolution of the effusion was
      achieved in 76% of the patients: such an effect could be due to the local
      antineoplastic activity of the drug. We believe that mitoxantrone is effective in
      the treatment of malignant pleural effusion due to pleural involvement with
      sarcoma without causing significant local or systemic toxicity.

PMID- 8305972
TI  - Gamma-probe-guided lymph node localization in malignant melanoma.
AB  - The initial draining lymph node (sentinel node) has been successfully localized
      using intraoperative vital dye mapping and reportedly is predictive of regional
      nodal metastases in Clinical- Stage 1 melanoma. In an animal model, we previously
      established the technique of gamma-probe-guided localization of the technetium-99
      sulfur colloid labelled sentinel node and found its sensitivity equal to vital
      dye mapping. We now report our initial experience using gamma-probe-guided
      localization to identify and then surgically remove the first draining lymph
      node(s) in 10 malignant melanoma patients. Lymphoscintigraphy was used to confirm
      localization. We conclude that this technique: (a) reliably localizes the
      sentinel node draining the site of a primary melanoma, (b) allows the lymphatic
      bed to be checked intraoperatively verifying complete sentinel node biopsy, and
      (c) is relatively simple and can be performed under local anaesthesia.

PMID- 8305973
TI  - Congenital vascular defects or malformations (CVMs)

PMID- 8305974
TI  - Epidemiology and etiology of congenital vascular malformations.

PMID- 8305975
TI  - Cutaneous vascular anomalies.

PMID- 8305976
TI  - Anatomopathological classification of congenital vascular defects.
AB  - 1. The proposed classification of congenital vascular defects based on anatomic
      and pathological features has proved to be useful in clinical practice. It is
      valid for vascular defects in all locations (central, visceral and peripheral),
      includes all types and anatomic forms of vascular malformations, yet is quite
      simplified. 2. A uniform and universal classification system is necessary for
      clear communication between the many different specialists dealing with
      congenital vascular defects. 3. It offers a clear and precise descriptive system
      to serve as the basis for diagnosis of congenital vascular defects. 4. A unified
      classification system offers the possibility of uniform analysis and comparative
      reporting between scientific investigators working in this field around the
      world.

PMID- 8305977
TI  - Congenital vascular malformations: diagnostic evaluation.
AB  - The management of CVMs is indeed difficult and is particularly frustrating
      because in most cases, complete cure or long-lasting control is not often
      possible by surgery or embolotherapy. However, the majority of patients with
      peripheral CVMs can be well-managed by conservative measures with only occasional
      intervention, and this provides some consolation. Nevertheless, it is important
      to be able to make a reasonable prognosis and set forth a therapeutic plan to the
      patient or the patient's parents, when the patient first presents. The approach
      recommended here allows one to establish the appropriate diagnosis and classify
      the CVM according to its vascular components. In addition, by assessing its
      hemodynamic or physiological effects and defining its anatomic extent and
      involvement of adjacent structures, one is in a position to provide definitive
      advice at the outset and continue to follow and manage the patient in a logical
      fashion using angiography sparingly, often only before the ultimately needed
      therapeutic intervention.

PMID- 8305978
TI  - Differential diagnosis in congenital vascular-bone syndromes.
AB  - Congenital vascular-bone syndrome is an alteration in limb growth caused by
      congenital vascular malformations in childhood. A precise study of the anatomic
      and hemodynamic nature of the underlying defect is necessary, not only for
      diagnosis, but also for therapy. The use of old eponyms for diagnosis, such as
      "Klippel-Trenaunay," "Parkes-Weber," and "Servelle-Martorell" should be abandoned
      because they are meaningless and misleading. An anatomic/pathological
      categorization, according to the simple "Hamburg classification," is more
      practical for clinical purposes. Seven different types of vascular defects, all
      associated with a-v fistulas, are related with limb overgrowth. Four different
      types of vascular malformations may produce limb shortening. Complete diagnostic
      study should allow classifying the malformation into one of the groups listed and
      illustrated above. Precise diagnosis is useful because interventional therapy can
      correct limb length discrepancy if performed before epiphyseal closure.

PMID- 8305979
TI  - Correction of lower limbs length discrepancy in congenital vascular-bone diseases
      by vascular surgery performed during childhood.
AB  - The progress in the treatment of congenital vascular-bone diseases in lower
      extremities caused by vascular malformations has been reviewed, along with an
      analysis of our clinical material and methods of treatment, and the results of
      our attempts to correct lower limb length discrepancy by early and direct
      vascular surgery directed at the cause of the bony changes. This experience leads
      us to the following conclusions: 1. Congenital vascular-bone diseases in lower
      extremities have a hemodynamic pathogenesis. The resulting bone changes can be
      caused by each of the different types of congenital vascular defects, or by a
      combination of them, with the resultant bone elongation or shortening due to
      hemodynamic and metabolic effects on the bone growth areas. 2. The recommended
      approach demands early, active, and causal treatment. 3. Operative techniques
      must be individualized and often seem unconventional because of the polymorphism
      of congenital vascular defects and specific differences in their anatomic and
      hemodynamic features. In severe cases, vascular surgery must be combined with
      other non-hemodynamic operations and nonsurgical methods (eg, orthopedic surgery,
      embolotherapy). 4. Early and active vascular surgery in childhood allows the
      correction of congenital lower limb length discrepancy, as judged by late follow
      up evaluation.

PMID- 8305980
TI  - Surgical treatment of predominantly venous defects.

PMID- 8305981
TI  - Combined treatment of congenital vascular defects: indications and tactics.
AB  - Congenital AV shunting defects are not as rare as sometimes presumed, and they
      are four times more frequent in girls than in boys. Inadequate treatment can
      aggravate the patient's complaints by increasing the circulatory disturbance in
      the affected region. As a result, ischemic ulceration may develop. Special,
      usually interdisciplinary, treatment of such findings is mandatory. When AV
      communications are present, the combined treatment of surgical and nonsurgical
      techniques must be considered. Location and pathoanatomic type influence this
      choice. Clinical, functional, and hemodynamic parameters must also be evaluated
      in order to decide the optimal combination of therapeutic measures. Usually
      several phases of treatment are necessary.

PMID- 8305982
TI  - Treatment of congenital vascular malformations of the face.

PMID- 8305983
TI  - Vaso-occlusive angiotherapy (VAT) in congenital vascular malformations.

PMID- 8305984
TI  - "Paradoxical" AH shortening caused by proximal coronary sinus stimulation during
      orthodromic reciprocating tachycardia.
AB  - INTRODUCTION: During extrastimulation or entrainment of orthodromic
      atrioventricular (AV) reciprocating tachycardia (ORT), the atrium-His (AH)
      interval as measured at the His-bundle recording site is expected to lengthen due
      to extrastimulation-dependent or pacing rate-dependent slowing of AV nodal
      conduction by impulses that penetrate the tachycardia circuit. We report 6
      patients in whom the AH interval "paradoxically" shortened during ORT in response
      to extrastimulation and rapid pacing from the proximal coronary sinus. METHODS
      AND RESULTS: Accessory pathway location was right anterior (1 patient), right
      anteroseptal (1 patient), and left anterior (4 patients). Cycle length of ORT was
      stable (variation < or = 5 msec) and ranged from 325 to 410 msec. During ORT,
      extrastimulation and rapid pacing were performed from the proximal coronary sinus
      and the right atrium. Extrastimulation from the proximal coronary sinus late in
      diastole caused significant shortening of AH interval in all patients by a mean
      of 18 +/- 3 msec (range 15 to 20 msec). AH shortening was demonstrated without a
      change of either the timing or morphologic appearance of the low septal right
      atrium at the His-bundle recording site. This phenomenon was not observed during
      right atrial extrastimulation. Rapid pacing from the proximal coronary sinus at
      cycle lengths of 305 to 390 msec (i.e., 15 to 20 msec shorter than the cycle
      length of each ORT) again demonstrated shortening of AH interval in all patients
      by a mean of 15 +/- 3 msec (range 10 to 20 msec). By contrast, rapid pacing from
      the right atrium demonstrated classical AH prolongation at any paced cycle
      length. CONCLUSION: AH shortening without a change of either the timing or
      morphologic appearance of the low septal right atrium at the His-bundle recording
      site confirms the existence of a distinct posterior atrial input to the AV node.
      In this setting low septal right atrial activation is not requisite for AV nodal
      conduction. Whether activation of the low septal right atrium is essential for,
      or contributes to, AV nodal conduction of atrial impulses from locations other
      than the proximal coronary sinus needs to be determined.

PMID- 8305985
TI  - Spontaneous activity in transgenic mouse heart: comparison of primary atrial
      tumor with cultured AT-1 atrial myocytes.
AB  - INTRODUCTION: We have generated transgenic animals that heritably develop atrial
      tumors composed of differentiated proliferating cardiomyocytes. Experiments were
      initiated to characterize the electrical properties of these cells. METHODS AND
      RESULTS: We show that the primary atrial tumors are composed of discrete foci
      that exhibit spontaneous automatic activity. A direct correlation was observed
      between tumor size and firing rate of these foci. In addition to the primary
      atrial tumors, we examined the properties of cultured cardiomyocytes isolated
      from a transplantable transgenic tumor lineage (designated AT-1 cells). Cultured
      AT-1 cells are also spontaneously automatic. The action potential configuration
      from these preparations is similar to that observed in nontransgenic atrial
      cardiomyocytes, albeit somewhat more depolarized and of longer duration. As would
      be expected for cardiomyocytes of atrial origin, the transgenic cardiomyocyte
      preparations hyperpolarize during muscarinic stimulation due to increased K+
      conductance mediated by a pertussis toxin sensitive G-protein. Assessment of
      pharmacologic blockage of the "if" pacemaker current suggests that the
      automaticity of both transgenic cardiomyocyte preparations may be of novel
      origin. In this context, the cultured AT-1 cells showed spontaneous behavior that
      was clearly of cellular origin; this activity was manifest as transient bursts of
      electrical activity followed by periods of electrical quiescence. This bursting
      pattern is unusual for normal adult cardiomyocytes, but has been observed in
      several other cell types. In the primary tumors, automatic behavior may arise
      from a similar cellular origin or alternatively from a microreentrant phenomena.
      CONCLUSION: Primary tumors and AT-1 cells show essential atrial electrophysiology
      with important novel features.

PMID- 8305987
TI  - Endocardial mapping of reentry around an anatomical barrier in the canine right
      atrium: observations during the action of the Class IC agent, flecainide.
AB  - INTRODUCTION: Flecainide is effective in terminating stable atrial flutter in the
      conscious dog with a Y-shaped right atrial lesion. In this model, flutter is due
      to circus movement of the impulse around a fixed anatomical barrier. METHODS AND
      RESULTS: To investigate the mechanism of flecainide-induced termination of this
      type of reentry, we determined the pattern of endocardial activation of the right
      and left atria before and during administration of flecainide by recording
      simultaneously from 192 electrode pairs in the isolated blood perfused heart. At
      least five consecutive flutter beats were analyzed before and during flecainide
      for each of eight termination episodes in five hearts. In all, flecainide
      increased flutter cycle length (164 +/- 24 msec) by 89% to 309 +/- 77 msec (P <
      0.05) before termination. Atrial refractory period and conduction time during
      paced beats were also increased by flecainide. In five episodes, termination was
      due to conduction block of the impulse at critical sites within the reentrant
      circuit (mode 1). Cycle length oscillations (+/- 30 msec) at sites proximal to
      site of block preceded termination in three of these episodes. In three other
      episodes, interruption of the original circuit occurred when there was failure of
      a lateral boundary, giving rise to an impulse that reset the original circuit
      (mode 2). In these episodes, long-short cycle length oscillations led to return
      reexcitation by the impulse within the primary path and subsequent termination.
      CONCLUSION: In summary, similar to our previous findings with the Class III
      agent, d-sotalol, two different modes of termination of atrial reentry were
      observed with flecainide.

PMID- 8305986
TI  - Effect of rate on changes in conduction velocity and extracellular potassium
      concentration during acute ischemia in the in situ pig heart.
AB  - INTRODUCTION: The purpose of our study was to determine if the slowing of
      longitudinal intraventricular conduction in the in situ porcine heart during
      acute regional no-flow ischemia was rate dependent. Further, we investigated
      whether any rate dependence could be correlated to a rate-dependent component of
      the ischemia-induced rise in extracellular potassium concentration, [K+]e.
      METHODS AND RESULTS: We studied in situ hearts in nine anesthetized open chest
      pigs in which acute no-flow ischemia was induced by occlusion of the left
      anterior descending coronary artery. To determine the effects of steady-state
      rate on the slowing of conduction and rise in [K+]e during ischemia, we varied
      the rate of stimulation during sequential occlusions from 90 to 150 beats/min.
      Longitudinal conduction velocity was determined by unipolar electrodes embedded
      in a plaque that was sutured to the epicardial surface in the center of the
      ischemic zone. Myocardial [K+]e was determined simultaneously by potassium
      sensitive electrodes placed at or within 1 to 2 mm of the epicardium in close
      proximity to the activation recording electrodes. Conduction velocity decreased
      more rapidly at the more rapid rates of stimulation although the reduction in
      conduction velocity occurring prior to the onset of conduction block was similar
      at both rates. The potassium change was not rate dependent and rose at the same
      rate regardless of the rate of stimulation. CONCLUSION: Our study demonstrates
      that the steady-state rate-dependent component of the slowing of intraventricular
      conduction induced by acute ischemia in the in situ porcine heart occurs in the
      absence of a rate-dependent component in the rise of [K+]e. Between rates of 90
      and 150 beats/min, the rate dependence of the conduction slowing may be
      attributed to one or more potassium-independent factors such as the rate
      dependent changes in resting membrane potential, in Vmax of the action potential
      upstroke, and in cell-to-cell uncoupling, which have been observed in other
      models of acute ischemia.

PMID- 8305989
TI  - Double retrograde atrial response after radiofrequency ablation of typical AV
      nodal reentrant tachycardia.

PMID- 8305988
TI  - Modification of sodium channel inactivation by alpha-chymotrypsin in canine
      cardiac Purkinje cells.
AB  - INTRODUCTION: Studies of tetrodotoxin-sensitive sodium current (INa) after
      modification of inactivation by intracellular enzymes in mammalian cells have
      demonstrated a marked increase in peak INa at test potentials near current
      threshold causing a large, negative shift of the peak INa conductance-voltage
      relationship by approximately -20 mV. These findings support a kinetic model in
      which the unmodified Na channel has rapid and voltage-independent inactivation
      from the open state. However, the kinetics of cardiac Na channels differ from
      those of mammalian neuronal Na channels. In particular, inactivation of cardiac
      Na channels has been proposed to be more voltage dependent than that of
      tetrodotoxin-sensitive Na channels. To help understand the role of inactivation
      in cardiac Na channel kinetic behavior, we studied Na currents before and after
      modification of inactivation by the proteolytic enzyme, alpha-chymotrypsin.
      METHODS AND RESULTS: Whole cell INa was measured in single canine cardiac
      Purkinje cells that were voltage clamped and internally perfused with a large
      bore suction pipette. The decay of INa in response to step depolarizations was
      dramatically slowed after perfusion with intracellular alpha-chymotrypsin
      consistent with modification of inactivation. In contrast to mammalian
      tetrodotoxin-sensitive Na current, Boltzmann distribution fits to peak INa
      conductance-voltage (GNa-V) relationships after alpha-chymotrypsin showed no
      change in either the potential at half maximum conductance (V 1/2), after
      correction for the spontaneous background shift of INa kinetics, or in the
      voltage-dependence of conductance (i.e., slope factor of GNa-V relationships).
      Maximal peak INa conductance increased by 18%. INa tail-current relaxations at
      potentials < or = -110 mV, after correction for spontaneous shifts in Na channel
      kinetics, were also similar before and after modification by alpha-chymotrypsin.
      CONCLUSION: alpha-chymotrypsin modified inactivation of cardiac INa with little
      or no change in activation, and cardiac Na channel inactivation was slow near
      threshold and played little role in determining V1/2 for peak INa conductance
      voltage relationships.

PMID- 8305990
TI  - Congenital disorders of cardiac rhythm and conduction.
AB  - Electrical instability of the heart has numerous congenital origins. This review
      approaches the problems from a morphological standpoint, utilizing selected
      examples from my own studies of the human cardiac conduction system performed
      during the last three decades. Subjects discussed include multifocal Purkinje
      cell tumors, benign congenital polycystic tumors of the AV node, several types of
      congenital heart block, postnatal morphogenesis of the AV node and His bundle
      (including considerations of persistent fetal dispersion and crib death), the
      Wolff-Parkinson-White syndrome, left superior vena cava, focal fibromuscular
      dysplasia of small coronary arteries, hereditary neuromuscular or musculoskeletal
      diseases, familial atrial fibrillation, long QT syndrome, and apoptosis of the
      heart. In many congenital disorders of cardiac electrical activity, both
      arrhythmias and conduction disturbances may occur. How the abnormal anatomy may
      relate to cardiac electrical instability is discussed, including certain clinical
      matters to be considered.

PMID- 8305991
TI  - Influence of ANP on sympathetic nerve activity and chronotropic regulation of the
      heart.
AB  - Hypotension caused by atrial natriuretic peptide (ANP) is often not accompanied
      by the anticipated increases in heart rate or sympathetic nerve activity. The
      sympathetic inhibitory action of ANP occurs in cardiac and noncardiac sympathetic
      nerves, and has been demonstrated in conscious or anesthetized animals as well as
      in humans. The sympathetic inhibition by ANP occurs after atropinization but is
      abolished after vagotomy. Thus, ANP alters sympathetic nerve activity by
      influencing cardiopulmonary baroreceptors, which in turn is mediated by vagal
      afferents. In addition to the effects of ANP on cardiopulmonary baroreceptors,
      ANP affects arterial baroreceptors. ANP dilates the ascending aorta where some of
      the arterial baroreceptors are located, causing resetting of these arterial
      baroreceptors. When ANP is microinjected into the cerebroventricle or nucleus
      tractus solitarii, it causes inhibition of sympathetic nerve activity. It has
      been shown that ANP inhibits sympathetic ganglionic transmission and augments
      cardiac parasympathetic effects on heart rate. Thus, ANP may play important roles
      in cardiovascular regulation by influencing sympathetic nerve activity and heart
      rate in addition to the direct vasodilating and renal effects.

PMID- 8305992
TI  - Spiral wave activity: a possible common mechanism for polymorphic and monomorphic
      ventricular tachycardias.
AB  - Several mechanisms have been proposed to explain the electrocardiographic
      patterns observed during various forms of polymorphic ventricular tachycardias,
      including torsades de pointes. Such mechanisms include the coexistence of either
      multiple foci or multiple exit pathways from single foci giving rise to various
      forms of aberrant ventricular activation sequences. For example, the simultaneous
      firing of two widely spaced foci at slightly different frequencies has been used
      to explain the undulating electrocardiogram that is characteristic of torsades de
      pointes. However, in spite of some supporting experimental evidence, such an idea
      remains conjectural from the clinical point of view. Here I discuss a mechanism
      that has been proposed recently to explain both monomorphic and polymorphic
      patterns (including undulating patterns) of ventricular tachycardia. The
      hypothesis is derived from the theory of spiral wave activity in excitable media,
      and from recent experiments using high resolution optical mapping in isolated two
      dimensional ventricular muscle preparations that demonstrate that spiral wave
      activity may account for self-sustaining reentrant activation. Such studies have
      led to the observation that the behavior of the spiral center, the core, plays a
      key role in determining the electrocardiographic manifestation of the arrhythmia.
      Indeed, a stationary position of the core results in a monomorphic pattern of
      activation. On the other hand, beat-to-beat changes in the core position (i.e.,
      drifting) leads to irregular patterns of activation. In fact, when drifting
      occurs in one direction, it gives rise to a Doppler shift in the excitation
      period in such a way that two coexisting frequencies are manifest, one ahead of
      and one behind the drifting core. The activation frequency in the region ahead of
      the core is always higher than that behind the core. Under such conditions,
      electrocardiographic recordings of the activity demonstrate an undulating
      pattern, which resembles that of torsades de pointes. When the core drifts in
      various directions, a polymorphic pattern is manifest. Thus, depending on spiral
      core dynamics, monomorphic, undulating, or completely irregular patterns may be
      observed. Moreover, transitions between such patterns can also occur. For
      example, drifting spirals giving rise to polymorphic activation can become
      stationary and result in monomorphic activation as a result of anchoring of the
      core to a small discontinuity (e.g., an artery or small scar) in the tissue.
      Direct extrapolation of such results to clinical cases is not appropriate.
      However, the observations discussed in this article offer a new testable
      hypothesis in which a common mechanism is postulated for the electrocardiographic
      patterns associated with monomorphic and polymorphic tachycardias.

PMID- 8305993
TI  - Is proper methodology associated with the use of a clinically relevant outcome
      measure? The case of randomized clinical trials on medical treatment of open
      angle glaucoma.
AB  - OBJECTIVE: The aim of this study was to assess critically the published
      literature concerning medical treatment of primary open-angle glaucoma (POAG),
      and to see whether trial methodologic quality was related to a clinically
      relevant outcome measure. METHODS: We identified and reviewed the methodologic
      quality of 102 published randomized clinical trials (RCTs) on treatment of POAG
      using an explicit protocol and explored the association between selected aspects
      of design and conduct and the studies' clinical relevance. RESULTS: Our analysis
      revealed serious methodologic problems with the trials reviewed. Areas of major
      concern were: use of unsatisfactory or unspecified methods of randomization (89%
      of the trials reported no information), exclusion of some patients from the
      analysis (53% of the studies), failure to provide evidence of having estimated
      the number of patients needed to detect a prespecified treatment difference (96%
      failed to provide such an estimate), and incomplete description of patient
      characteristics (in 39% of the RCTs information on this item was insufficient).
      Within this generally unsatisfactory picture we found, however, that those
      studies adopting a double-masked design and those not excluding patients after
      randomization followed patients for longer periods of time and assessed treatment
      effectiveness using a clinically relevant outcome (that is, visual field changes)
      compared to other studies. CONCLUSIONS: For clinicians to make use of the results
      of clinical trials, future studies must be adequately designed and conducted. In
      particular, proper method of randomization, masking of the observers, and
      inclusion of all randomized patients in the analysis must be used. Of perhaps
      even greater importance is the need for trials to measure clinically relevant
      outcomes.

PMID- 8305994
TI  - The ABCD (Appropriate Blood Pressure Control in Diabetes) trial. Rationale and
      design of a trial of hypertension control (moderate or intensive) in type II
      diabetes.
AB  - OBJECTIVE: The primary objective of the ABCD (Appropriate Blood Pressure Control
      in Diabetes) Trial is to determine the efficacy of intensive versus moderate
      antihypertensive control on the outcome of type II diabetic end-organ
      complications in normotensive and hypertensive populations. The secondary
      objective is to determine whether any differential effect on end-organ
      complications exists between an angiotensin converting enzyme inhibitor
      (enalapril) and a calcium channel blocker (nisoldipine). DESIGN: The ABCD Trial
      is a prospective, controlled, randomized, double-blind trial, with a planned
      follow-up of 5 years. SETTING: All patients are seen at the Colorado Prevention
      Center, site of the ABCD Trial, for follow-up visits. PATIENTS: Patients are type
      II diabetic males and females between the ages of 40 and 74 years with entry
      diastolic blood pressures > or = 80 mmHg. Patients were recruited from University
      of Colorado-affiliated hospitals, several health maintenance organizations, and
      mailing lists from the Colorado affiliate of the American Diabetes Association.
      INTERVENTIONS: Patients were randomized to intensive antihypertensive drug
      therapy or moderate antihypertensive drug therapy. Patients were also randomized
      to nisoldipine or enalapril, with open-label medications added if further blood
      pressure control was necessary. MAIN OUTCOME MEASURES: The primary outcome
      measure is glomerular filtration rate as assessed by 24-hour creatinine
      clearance. Secondary outcome measures are microalbumin urinary excretion, left
      ventricular hypertrophy, retinopathy, and neuropathy. Cardiovascular morbidity
      and mortality will also be evaluated. CONCLUSION: Given the data showing the
      impact of hypertension on diabetic complications, the ABCD Trial was designed to
      determine if intensive antihypertensive therapy will be more efficacious than
      moderate antihypertensive therapy on the outcome of these complications. Results
      from the ABCD Trial are expected to lend interpretable and clinically relevant
      findings with regards to the treatment of hypertension in type II diabetes.

PMID- 8305995
TI  - Squeezing the turnip. The need for outcomes studies of antihypertensive
      therapies.

PMID- 8305996
TI  - Periventricular/intraventricular hemorrhage following early and delayed umbilical
      cord clamping. A randomized controlled trial.
AB  - OBJECTIVE: To test the hypothesis that early compared with delayed clamping of
      the umbilical cords of low-birthweight babies may increase the incidence of
      periventricular/intraventricular hemorrhage (PVH/IVH). DESIGN: Randomized
      controlled trial. SETTING: The labor wards of 3 teaching hospitals of the
      University of the Witwatersrand, Johannesburg. PATIENTS: Women expected to give
      birth to babies weighing less than 2000 g. INTERVENTIONS: Allocation by randomly
      ordered, sealed cards to a policy either of clamping the umbilical cord
      immediately after delivery, or, if possible, delaying cord clamping for 1 to 2
      min. MAIN OUTCOME MEASURES: Ultrasound diagnosis of PVH/IVH about 24 h after
      birth by an observer blind to the allocation of each patient. RESULTS: PVH/IVH
      was diagnosed in 8/40 (20%) of neonates following delayed umbilical cord clamping
      and 11/46 (24%) following early cord clamping (odds ratio 0.80; 95% confidence
      interval, 0.29 to 2.20). CONCLUSIONS: This study does not confirm that early
      clamping of the umbilical cord may contribute to the initiation of PVH/IVH in low
      birthweight neonates, but further studies are required before the hypothesis can
      be rejected with confidence.

PMID- 8305997
TI  - Adjuvant adoptive immunotherapy for pediatric recurrent brain tumors.

PMID- 8305998
TI  - The effectiveness of nicotine replacement therapies in smoking cessation.
AB  - OBJECTIVE: To determine the effectiveness of nicotine replacement therapies
      (NRTs) (including gum, transdermal patch, intranasal spray, and inhaled
      preparations) in facilitating smoking cessation, and to determine whether the
      effect was influenced by the clinical setting in which the smoker was recruited
      and treated, the level of nicotine dependency, the dosage of NRT used, or the
      intensity of additional advice and support offered to the smoker. DATA SOURCES:
      Published trials of NRT were identified by a systematic search of 7 electronic
      databases, published reviews, reference lists from clinical trials, conference
      abstracts, smoking and health bulletins, and a bibliography on smoking and
      health. Unpublished trials were identified by approaching manufacturers of NRT.
      STUDY SELECTION: A total of 53 trials (42 gum, 9 patch, 1 intranasal spray, and 1
      inhaler), with data from 17,703 patients, were included in the analyses. Only
      trials that assessed abstinence at least 6 months after the commencement of
      therapy were included. DATA EXTRACTION: Data were extracted from the trial
      reports by 2 authors independently. Where the methodology was unclear or the
      results were not expressed in a form which allowed extraction of key data we
      wrote to the investigators for the required information. DATA SYNTHESIS: Use of
      NRT increased the odds ratio (OR) of abstinence to 1.71 (95% confidence interval
      [CI], 1.56 to 1.87) compared with those who had been allocated to the control
      interventions. The OR for the different forms of NRT were 1.61 for nicotine gum
      (95% CI, 1.46 to 1.78), 2.07 (95% CI, 1.62 to 2.62) for transdermal patch, 2.92
      (95% CI, 1.49 to 5.74) for nasal spray, and 3.05 for inhaled nicotine (95% CI,
      1.42 to 6.57). These odds were not significantly higher in patients with higher
      levels of nicotine dependence (Fagerstrom score > or = 7; P = 0.06), but they
      were largely independent of the intensity of additional support provided or the
      setting in which the NRT was offered. CONCLUSION: We conclude that the currently
      available forms of NRT are effective therapies to aid smoking cessation.

PMID- 8305999
TI  - The effectiveness of breast cancer screening by mammography in younger women.
AB  - We reviewed the evidence relating to breast screening using mammography in
      younger women, primarily those aged 40 to 49. The best evidence comes from the 6
      published randomized trials. We performed a metaanalysis, assessing the breast
      cancer death rates for each year of follow-up in each trial, and producing
      summary estimates of the cumulative and year-specific mortality rates. At 7 to 10
      years, death rates in screened and unscreened groups are similar. This lack of
      benefit contrasts with the average 30% mortality reduction in women over age 50
      in the same trials. This evidence provides no basis for the promotion of
      mammographic screening in women under age 50 in the general population. If
      mammography is to be offered to asymptomatic women of that age who request it,
      appropriate information including the fact that there has been no demonstrated
      ultimate benefit should be given. The difference in effectiveness may relate both
      to the greater difficulty in distinguishing normal from abnormal tissue, and to
      greater growth speed and different biological characteristics of tumors, in
      younger women. We also reviewed recommendations from major groups: in general
      multidisciplinary bodies which rely on structured evaluations do not recommend
      screening in younger women, while many other specialty associations and cancer
      societies do. Overall, the trials of screening of younger women show a small
      increase in mortality in those screened, and possible explanations of this are
      discussed. [corrected] Remaining questions concern the precise age at which
      effectiveness changes, the situation in high-risk women, and the impact of
      improved or more frequent screening.

PMID- 8306000
TI  - A high-yield strategy to identify randomized controlled trials for systematic
      reviews.
AB  - OBJECTIVE: To compare the sensitivity, precision, and the costs in time of
      searching by hand and by MEDLINE to identify randomized controlled trials (RCTs)
      for systematic reviews. DESIGN: Nine anesthetic and pain journals were searched
      by both MEDLINE and by hand for the years 1970, 1980, and 1990, recording number
      of publications and time taken to identify randomized double-blind controlled
      trials in pain research. RESULTS: Thirty-four volumes, containing 5583 full
      publications (24,417 pages) and 2889 abstracts and letters (1755 pages) were hand
      searched; 142 eligible (definite RCTs) full papers and 171 eligible abstracts and
      letters were identified. The MEDLINE search strategy yielded 274 reports of which
      138 were eligible; 125 of these were full papers, 1 was a letter and 12 were
      abstracts. Two full papers which were identified by the MEDLINE search strategy
      were missed by hand search. The overall sensitivity of the MEDLINE search
      strategy for full papers was 87% ([125/144] x 100) with a precision of 52%
      ([125/242] x 100). This is the best combination of sensitivity and precision
      reported to date. Abstracts were mostly in supplement issues which were not
      indexed. Combining the MEDLINE search strategy with selective hand search of
      abstracts and letters gave a sensitivity of 94%. CONCLUSIONS: Hand search of
      entire journals remains the most accurate method for identification of the
      eligible reports, but it is the most time-consuming. The MEDLINE search was
      faster, but it failed to identify at least 13% of the indexed eligible reports.
      Ideally, both hand search and MEDLINE should be used. The combination of MEDLINE
      with hand search restricted to letters and abstracts might be an acceptable
      alternative for reviewers with insufficient funds to support a full hand search
      process.

PMID- 8306001
TI  - Local anesthesia by peribulbar block for cataract extraction in an eye relief
      camp. A double-masked, randomized controlled trial.
AB  - OBJECTIVE: To test the hypothesis that the median scores for globe anesthesia are
      not significantly different for patients receiving local anesthesia (LA) by
      peribulbar block (PB) than for those receiving retrobulbar block (RB) for
      cataract surgery. DESIGN: Double-masked, randomized controlled trial. SETTING: An
      eye camp in Bhetwa, India, base hospital was King George's Medical College,
      Lucknow. (Eye camps are temporary set-ups used for cataract surgery throughout
      rural India.) Study carried out over a 2-day period. PATIENTS: Out of 125
      patients eligible for intracapsular cataract extract on under LA, 122 agreed to
      enter the trial, and were randomly allocated to 2 groups just before the
      operation. The groups were equal in size and similar in composition in terms of
      patient age and sex. INTERVENTION: PB or RB infiltrated with 5 mL of the same
      anesthetic at the same site but with a different needle size and direction. MAIN
      OUTCOME MEASURES: Globe anesthesia (primary outcome), globe akinesia, lid
      akinesia, pupillary dilatation, and hypotony were scored separately on a 4-point
      scale during surgery by a masked surgeon. During infiltration, surgery, and the
      1st 30 minutes after surgery, pain was scored by patients and recorded by an
      interviewer. RESULTS: Median scores for globe anesthesia were 4.0 in both groups,
      and the Mann-Whitney test revealed no difference in the medians of these scores
      (P = 0.6). There was no difference in scores on other outcomes measured, except
      lid akinesia, which was better with PB. Subjective pain scores were significantly
      higher with RB. The surgeon's guess about the type of LA administered was correct
      only for 58% of patients. CONCLUSION: PB is no different from RB in terms of
      producing globe anesthesia when used for cataract surgery at eye camps.

PMID- 8306002
TI  - Response to Kopans.

PMID- 8306003
TI  - Problems in interpreting cost effectiveness in clinical trials. Experimental
      versus implementation costs.
AB  - OBJECTIVE: To demonstrate the difficulty of estimating cost effectiveness of
      alternative implementation strategies using clinical trial data. DESIGN: Two
      examples drawn from a hearing-aid intervention trial and a physical-therapy trial
      for frail elderly are used to demonstrate how alternative implementation
      strategies may affect cost effectiveness. Sensitivity analysis is used to
      document a range of possible economic outcomes for each example and show how
      assumptions based on trials may bias implementation decisions. MAIN OUTCOME
      MEASURES: Costs and cost-effectiveness ratios are estimated for alternative
      implementation strategies and compared with trial results. MAIN RESULTS: Staffing
      and equipment substitutions, reconfigurations, and economies of scale can reduce
      the cost of trial interventions substantially. Such resource alterations as well
      as protocol and target group modifications may also have an impact on
      effectiveness. In both examples effectiveness can be reduced by as much as 50%
      and under certain conditions alternative implementation strategies will still be
      cost effective. CONCLUSIONS: Cost effectiveness of implementations can differ
      substantially from a trial when different resources or target populations are
      incorporated. Institutions must conduct preimplementation studies which consider
      alternative resource configurations before adopting an intervention based on
      trial results.

PMID- 8306004
TI  - Rejoinder to Elwood's reply.

PMID- 8306005
TI  - NIH clinical trials and publication bias.
AB  - OBJECTIVE: To investigate the association between trial characteristics,
      findings, and publication. The major factor hypothesized to be associated with
      publication was "significant" results, which included both statistically
      significant results and results assessed by the investigators to be qualitatively
      significant, when statistical testing was not done. Other factors hypothesized to
      have a possible association with publication were funding institute, funding
      mechanism (grant versus contract versus intramural), multicenter status, use of
      comparison groups, large sample size, type of control (parallel versus
      nonparallel), use of randomization and masking, type of analysis (by treatment
      received versus by treatment assigned), and investigator sex and rank. DESIGN:
      Follow-up, by 1988 interview with the principal investigator or surrogate, of all
      clinical trials funded by the National Institutes of Health (NIH) in 1979, to
      learn of trial results and publication status. POPULATION: Two hundred ninety
      three NIH trials, funded in 1979. MAIN OUTCOME MEASURE: Publication of clinical
      trial results. RESULTS: Of the 198 clinical trials completed by 1988, 93% had
      been published. Trials with "significant" results were more likely to be
      published than those showing "nonsignificant" results (adjusted odds ratio [OR] =
      12.30; 95% confidence interval [CI], 2.54 to 60.00). No other factor was
      positively associated with publication. Most unpublished trials remained so
      because investigators thought the results were "not interesting" or they "did not
      have enough time" (42.8%). Metaanalysis using data from this and 3 similar
      studies provided a combined unadjusted OR of 2.88 (95% CI, 2.13 to 3.89) for the
      association between significant results and publication. CONCLUSIONS: Even when
      the overall publication rate is high, such as for trials funded by the NIH,
      publication bias remains a significant problem. Given the importance of trials
      and their utility in evaluating medical treatments, especially within the context
      of metaanalysis, it is clear that we need more reliable systems for maintaining
      information about initiated studies. Trial registers represent such a system but
      must receive increased financial support to succeed.

PMID- 8306006
TI  - A program to enhance clinical use of MEDLINE. A randomized controlled trial.
AB  - OBJECTIVE: To determine if a preceptor and individualized feedback improves the
      performance of physicians in searching MEDLINE in clinical settings. DESIGN:
      Randomized controlled trial with 2 to 10 months follow-up. SETTING: A 300-bed
      teaching hospital. PARTICIPANTS: All 392 physicians and physicians-in-training
      from 6 major clinical departments were invited to participate if they made
      patient-care decisions during the study period; 79.4% agreed. INTERVENTIONS: All
      participants were given 2 hours of basic training, then randomized to a control
      group (no further intervention) or an intervention group in which each person
      chose a clinical preceptor experienced in MEDLINE searching and received
      individualized feedback from a study librarian on each of their 1st 10 searches.
      MAIN OUTCOME MEASURES: The number and proportion of relevant and irrelevant
      references retrieved for 1st, 4th, and 8th searches of participants were compared
      with independent librarian searches on the same topics. RESULTS: Intervention
      group members did not search more often than controls (5.9 searches per month
      versus 4.7, respectively; P = 0.26) and there were no significant differences in
      the quality of searches. Rather, search performance for both groups improved,
      with the average number of relevant references retrieved per search increasing
      from 4.5 to 7.4 (P < 0.01). The librarian retrieved more relevant citations than
      participants for the 1st search (P = 0.001) but not for the 4th (P = 0.60) or 8th
      (P = 0.76) searches. CONCLUSIONS: A program of assigning preceptors and providing
      feedback on individual searches did not enhance the quantity or quality of
      searches. Soon after a basic introduction to searching, however, clinicians in
      both groups improved their search performance.

PMID- 8306007
TI  - Metaanalysis of the effects of intensive glycemic control on late complications
      of type I diabetes mellitus.
AB  - OBJECTIVE: To estimate the effects of intensive glycemic control on the
      progression of diabetic retinopathy and nephropathy, and to assess the risks of
      severe hypoglycemia and diabetic ketoacidosis. DESIGN: Metaanalysis of published
      randomized controlled trials. SETTING: As listed in each study. PATIENTS: Five
      hundred twenty-nine patients from 16 randomized controlled trials. MEASUREMENTS:
      We searched for all studies with sufficient data for analysis. The overall
      difference in the risk of retinopathy or nephropathy progression was analyzed,
      and the overall difference in the incidence of hypoglycemia or diabetic
      ketoacidosis was estimated. RESULTS: Compared to conventionally treated patients,
      the risk of retinopathy progression was statistically insignificantly higher
      after 6 to 12 months of intensive therapy (odds ratio [OR] 2.11; 95% confidence
      interval [CI], 0.54 to 8.31). After more than 2 years of intensive therapy the
      risk of retinopathy progression was lower (OR 0.49; 95% CI, 0.28 to 0.85). The
      risk of nephropathy progression was also decreased significantly in the intensive
      therapy group (OR 0.32; 95% CI, 0.19 to 0.55). When compared to conventional
      control, intensive therapy reduced glycosylated hemoglobin (%) by 1.4 with a 95%
      CI ranging from 1.1 to 1.8. The overall incidence of severe hypoglycemia
      increased by 9.1 episodes/100 person-years (95% CI, -1.4 to 19.6) in the
      intensively treated patients. The incidence of diabetic ketoacidosis increased by
      12.6 episodes/100 person-years (95% CI, 8.7 to 16.5) in those who received
      continuous subcutaneous insulin infusion. CONCLUSION: Long-term intensive
      glycemic control significantly reduced the risks of diabetic retinopathy and
      nephropathy progression among type I diabetes patients when compared with
      randomly assigned controls. However, long-term continuous subcutaneous insulin
      infusion was associated with an increased incidence of diabetic ketoacidosis, and
      intensive therapy might cause more severe hypoglycemic reactions in some
      patients.

PMID- 8306008
TI  - Mammography after 30 years.

PMID- 8306009
TI  - Early angiography and angioplasty following thrombolytic therapy of acute
      myocardial infarction. Metaanalysis of the randomized control trials.
AB  - STUDY OBJECTIVE: There have been at least 10 randomized control trials (RCTs) of
      early intervention in patients with acute myocardial infarction published, and
      all are inconclusive with regard to impact on mortality. Metaanalysis offers an
      opportunity to assess the efficacy of an early intervention following
      thrombolytic therapy in the treatment of acute myocardial infarction. DESIGN:
      Data on the number of patients who died in the hospital, and the total number of
      patients randomized to aggressive versus conservative therapies, were drawn from
      9 publications and combined using both a fixed and a random-effects metaanalysis
      model. Quality of the trials was assessed under blinded conditions. SETTING: The
      10 RCTs to be combined were each carried out in individual institutions.
      PATIENTS: A total of 5882 patients have been randomized, with 305 deaths (5.2%),
      indicating that this group of patients had a relatively low mortality rate
      compared to patients in general with acute myocardial infarction. COMPARISON OF
      TREATMENTS: No matter how the 10 trials were combined for analysis, there was no
      evidence that aggressive intervention was trending towards saving lives. Data on
      other endpoints such as need for repeat percutaneous transluminal coronary
      angioplasty (PTCA), coronary artery bypass grafting (CABG), or recurrent
      myocardial infarction were sparse, but the same adverse trend was apparent.
      CONCLUSION: In spite of the fact that early angiography and PTCA when indicated
      have been advocated for more than a decade, there is still no evidence that they
      reduce overall mortality after fibrinolysis in a specific subgroup. Further
      studies of early intervention should be done in an effort to answer subgroup
      questions which include the search for appropriate timing and patient selection
      for PTCA after fibrinolysis. As more RCTs with mortality data are published they
      will be added to these metaanalyses in The Online Journal of Current Clinical
      Trials.

PMID- 8306010
TI  - In vitro fertilization and embryo transfer: a randomized controlled trial.
AB  - OBJECTIVE: The clinical indications for in vitro fertilization (IVF) have
      expanded to include many forms of infertility in addition to tubal disease.
      Pregnancies in IVF cycles are noteworthy but there is frequently a spontaneous
      cure for infertility among similar couples. The relative merit of IVF treatment
      over spontaneous cure or other forms of fertility treatment has not been
      rigorously evaluated. DESIGN: The study was a randomized controlled clinical
      trial comparing the clinical pregnancy rate among couples undergoing IVF with the
      rate among couples awaiting an IVF treatment. PATIENTS: Patients entering a
      provincially funded program of IVF were randomly allocated to a period of delay
      prior to IVF treatment (Control n = 194) or 1 or more cycles of IVF treatment
      (Experimental n = 205). MAIN OUTCOME MEASURES: Clinical pregnancy rate and
      adjusted time to pregnancy. RESULTS: In the Control group there were 13
      pregnancies. In the Experimental group there were 13 pregnancies before treatment
      could be arranged. There were 20 additional pregnancies in treatment cycles. The
      intention-to-treat analysis showed an increase in the proportion of pregnancies
      from 8% to 17.4% and parturition from 4.9% to 11.6%. Substantially more patient
      time (due to IVF) was required to achieve this increase. There was no difference
      between groups when time-to-event was considered by survival analysis, although a
      long-term trend in favor of the Experimental group was suggested. Low-event
      frequency and broad confidence intervals in Control patients prior to censor and
      transfer to IVF treatment prevented a conclusive assessment of the long-term
      benefits of IVF treatment. Generalizing these findings, improved effectiveness
      may be evident with delayed access to treatment (longer waiting lists), suitable
      candidates with appropriate primary clinical diagnoses and durations of
      infertility and higher rates of treatment over time (larger clinics).
      CONCLUSIONS: IVF treatment is effective in increasing, proportionally, the
      numbers of pregnancies, live births, and parturitions, but this occurred with
      significantly longer patient commitment.

PMID- 8306011
TI  - Cesarean section to reduce perinatal transmission of human immunodeficiency
      virus. A metaanalysis.
AB  - OBJECTIVE: Individual epidemiologic investigations into the association between
      type of delivery and perinatal HIV transmission have been suggestive but
      inconclusive. Metaanalysis was used in an attempt to establish if there is, at
      present, adequate evidence concerning the effectiveness of cesarean section in
      reducing vertical HIV transmission rates. METHODS: The MEDLINE data retrieval
      system and other sources were used to identify studies containing data on the
      relationship between type of delivery and vertical HIV transmission. No
      randomized control trials were located. Six cohort studies identified were
      included in the metaanalysis. Crude and, in the only study in which these were
      available, adjusted data were extracted and pooled. RESULTS: The overall weighted
      risk of perinatal HIV infection was 20.2% and 14.0% after vaginal and cesarean
      delivery, respectively. Pooling data of all studies showed a statistically
      significant difference of HIV perinatal transmission rates between cesarean and
      vaginal delivery (odds ratio 0.65; 95% CI, 0.43 to 0.99; P = 0.044) (Random
      effects model: DerSimonian and Laird method). Approximately 16 (95% CI, 76 to 9)
      HIV-infected women must deliver by cesarean in order to prevent 1 case of HIV
      perinatal infection. CONCLUSIONS: Results of this study show that performing
      elective cesarean section in HIV-infected women is potentially an effective
      procedure. However, the nonexperimental nature of the available studies leads us
      to conclude that randomized control trials are indicated before setting specific
      guidelines for mode of delivery in HIV-infected women.

PMID- 8306012
TI  - Data monitoring in the cardiac arrhythmia suppression trial.
AB  - OBJECTIVE: This report discusses practical aspects of data monitoring in a
      clinical trial which stopped ahead of schedule due to adverse findings. DESIGN: A
      review of the considerations and decisions made by the data-monitoring committee
      of the Cardiac Arrhythmia Suppression Trial (CAST), a randomized, double-blind
      clinical trial. PATIENTS: CAST consisted of men and women with a recent
      myocardial infarction, asymptomatic or minimally symptomatic ventricular
      arrhythmias, and reduced left ventricular ejection fraction. INTERVENTIONS: In
      CAST, 3 antiarrhythmic agents, encainide, flecainide, and moricizine, were
      compared against placebo. MAIN OUTCOME MEASURES: The main outcome measures in
      CAST were arrhythmic death and total mortality. RESULTS: CAST found the 3 agents
      to be harmful. Encainide and flecainide were stopped first. Subsequently,
      moricizine was discontinued ahead of schedule. CONCLUSIONS: The complexity of the
      study design and a midcourse protocol modification raise several data-monitoring
      issues not previously discussed. These include how to handle apparently dramatic
      yet unexpected results, the need for flexibility in modifying study design and
      goals, and the conflict between existing study data and both conventional wisdom
      and medical practice.

PMID- 8306013
TI  - The Salford Third Stage Trial. Oxytocin plus ergometrine versus oxytocin alone in
      the active management of the third stage of labor.
AB  - OBJECTIVES: To compare oxytocin plus ergometrine against oxytocin alone, when
      administered as part of the active management of the 3rd stage of labor, in terms
      of postpartum hemorrhage and manual removal of the placenta. DESIGN: A double
      blind, randomized controlled trial. SETTING: A university teaching hospital: Hope
      Hospital, Salford. PATIENTS: All women delivering in the hospital over the period
      of the trial, except those for whom a cesarean section was planned, or who had
      significant hypertension or cardiac disease. INTERVENTIONS: Syntometrine (5 units
      of oxytocin with 0.5 mg of ergometrine) versus 5 units of Syntocinon (oxytocin),
      both given by intramuscular injection with delivery of the anterior shoulder.
      MAIN OUTCOME MEASURES: Postpartum blood loss, the length of the 3rd stage of
      labor, and the need for manual removal of the placenta. RESULTS: Four hundred
      sixty-one women were recruited, 230 allocated to ergometrine plus oxytocin and
      231 to oxytocin alone. The duration of the 3rd stage of labor in each group was
      similar (difference in means 0.2 mins; 95% confidence interval [CI], -1.0 to 1.5)
      and the need for manual removal of the placenta (odds ratio [OR] 1.21; 95% CI,
      0.37 to 4.00). There was less postpartum blood loss in the oxytocin plus
      ergometrine group, reflected in the lower incidence of primary postpartum
      hemorrhage (> 500 mL) (OR 0.37; 95% CI, 0.16 to 0.85). CONCLUSIONS: Judged on the
      basis of this trial alone, oxytocin plus ergometrine is more effective than
      oxytocin alone in the prevention of postpartum hemorrhage. However, evidence from
      other trials shows that the ergometrine component not uncommonly has side effects
      of nausea, vomiting, and raised blood pressure. The implications for practice
      therefore depend on the relative weights placed on these competing risks by women
      and clinicians. Further research is needed to quantify these along with research
      into possible differential effects on longer-term outcomes and into the
      implications of a higher dose of oxytocin.

PMID- 8306014
TI  - The therapeutic prescription for the patient undergoing immunosuppressing
      therapy.

PMID- 8306016
TI  - Treatment of early or asymptomatic HIV infection. Where are we and where do we go
      from here?

PMID- 8306015
TI  - Clinical trial quality needs to be improved to facilitate metaanalyses.

PMID- 8306017
TI  - Ethics of monitoring patient adherence. An evolving dilemma.

PMID- 8306018
TI  - Monitoring for adherence: ethical considerations.

PMID- 8306019
TI  - Objective measurement of metered-dose inhaler use. Ethical considerations.

PMID- 8306020
TI  - Objective measurement of nasal continuous positive airway pressure use. Ethical
      considerations.

PMID- 8306021
TI  - An anecdote is an anecdote is an anecdote ... but a clinical trial is data.

PMID- 8306023
TI  - Acute effect of corticosteroids on respiratory mechanics in mechanically
      ventilated patients with chronic airflow obstruction and acute respiratory
      failure.
AB  - We assessed the short-term effect of steroids on respiratory mechanics in eight
      mechanically ventilated patients with chronic airflow obstruction (CAO) and
      hypercapnic respiratory failure. Airflow (V), airway pressure (Paw), and changes
      in pulmonary volume were measured using a conventional ventilator. End-expiratory
      and end-inspiratory airway occlusions were performed to assess intrinsic PEEP
      (PEEPi), static compliance of total respiratory system (Cstrs), maximum
      inspiratory resistance (Rrsmax), and minimum inspiratory resistance (Rrsmin).
      These parameters were recorded at control, 30 min after saline, and 90 min after
      steroid (methylprednisolone 0.8 mg/kg intravenous) administration. No significant
      changes were found in respiratory mechanics after administration of saline.
      Steroids induced a significant decrease (p < 0.01) in inspiratory resistance
      (Rrsmax from 20.3 +/- 8.6 cm H2O/L/s (control) to 15.3 +/- 6.1 (90 min) and
      Rrsmin from 16.2 +/- 8.0 (control) to 11.9 +/- 6.5 (90 min), with no significant
      reduction in Paw and Cstrs. The PEEPi, reflecting pulmonary dynamic
      hyperinflation, was also significantly reduced (-16% from control). We conclude
      that in mechanically ventilated CAO patients, steroids may be useful in improving
      respiratory mechanics and therefore in providing better conditions for weaning
      from mechanical ventilation.

PMID- 8306022
TI  - Randomized clinical trial of pressure-controlled inverse ratio ventilation and
      extracorporeal CO2 removal for adult respiratory distress syndrome.
AB  - The impact of a new therapy that includes pressure-controlled inverse ratio
      ventilation followed by extracorporeal CO2 removal on the survival of patients
      with severe ARDS was evaluated in a randomized controlled clinical trial.
      Computerized protocols generated around-the-clock instructions for management of
      arterial oxygenation to assure equivalent intensity of care for patients
      randomized to the new therapy limb and those randomized to the control,
      mechanical ventilation limb. We randomized 40 patients with severe ARDS who met
      the ECMO entry criteria. The main outcome measure was survival at 30 days after
      randomization. Survival was not significantly different in the 19 mechanical
      ventilation (42%) and 21 new therapy (extracorporeal) (33%) patients (p = 0.8).
      All deaths occurred within 30 days of randomization. Overall patient survival was
      38% (15 of 40) and was about four times that expected from historical data (p =
      0.0002). Extracorporeal treatment group survival was not significantly different
      from other published survival rates after extracorporeal CO2 removal. Mechanical
      ventilation patient group survival was significantly higher than the 12% derived
      from published data (p = 0.0001). Protocols controlled care 86% of the time.
      Average PaO2 was 59 mm Hg in both treatment groups. Intensity of care required to
      maintain arterial oxygenation was similar in both groups (2.6 and 2.6 PEEP
      changes/day; 4.3 and 5.0 FIO2 changes/day). We conclude that there was no
      significant difference in survival between the mechanical ventilation and the
      extracorporeal CO2 removal groups. We do not recommend extracorporeal support as
      a therapy for ARDS. Extracorporeal support for ARDS should be restricted to
      controlled clinical trials.

PMID- 8306024
TI  - Quantitative cultures of protected brush specimens and bronchoalveolar lavage in
      ventilated patients without suspected pneumonia.
AB  - Quantitative bacterial cultures of protected specimen brush (PSB) and
      bronchoalveolar lavage (BAL) specimens were used to assess the presence of distal
      bronchial microflora in mechanically ventilated patients who were not suspected
      of having pneumonia. A total of 54 specimens from 32 ICU patients were obtained.
      In 10 patients, only PSB specimens were recovered, whereas in 22 patients both
      PSB and BAL specimens were obtained. Cultures demonstrated no growth in 10 (45%)
      of the 22 samples recovered by BAL and in 21 (66%) of the 32 samples recovered by
      the PSB method. Twenty-three specimens yielded microorganisms, but in only six
      patients was a significant growth in PSB and/or BAL cultures (> or = 10(3) and >
      or = 10(5) cfu/ml, respectively) detected. Four of these patients developed
      pneumonia on subsequent follow-up. In mechanically ventilated patients, the
      diagnostic thresholds of bacterial growth in PSB and BAL cultures may be
      misleading. A significant relationship was found between the ability of PSB to
      recover microorganisms and the duration of mechanical ventilation (p < 0.05).
      These findings may be a limitation present in all patients receiving prolonged
      mechanical ventilation.

PMID- 8306025
TI  - Validation of different techniques for the diagnosis of ventilator-associated
      pneumonia. Comparison with immediate postmortem pulmonary biopsy.
AB  - To assess the accuracy of clinical parameters for the diagnosis of ventilator
      associated (VA) pneumonia, as well as the diagnostic value of several invasive
      techniques, such as protected specimen brush (PSB), bronchoalveolar lavage (BAL),
      fiberoptic bronchial aspirates (FBAS), and percutaneous lung needle aspiration
      (PLNA), we compared the results of these techniques with the histopathology of
      immediate postmortem pulmonary biopsies, considered the "gold standard" reference
      test. We studied 30 mechanically ventilated patients (age 52 +/- 21 yr;
      mechanical ventilation period 9 +/- 7 days) who died in an intensive care unit.
      All patients received prior antibiotic treatment. The following procedures were
      performed immediately after death: bilateral PSB, BAL, FBAS, and PLNA, as well as
      bilateral minithoracotomies to obtain pulmonary biopsies as close as possible to
      the area sampled with the other techniques. According to the histopathology 18
      patients had pneumonia and 12 did not. The presence of fever (sensitivity 55%,
      specificity 58%), purulent secretions (sensitivity 83%, specificity 33%), and
      chest radiograph infiltrates (sensitivity 78%, specificity 42%) could not
      differentiate in all instances presence from absence of pneumonia. Quantitative
      bacterial cultures of lung biopsies using 10(3) cfu/g as a cutoff point had low
      sensitivity (40%) and low specificity (45%) and could not differentiate the
      histologic absence or presence of pneumonia. Considering the histopathology of
      pulmonary biopsies as a gold standard, we found the following sensitivities for
      PSB, BAL, FBAS, and PLNA: 36, 50, 44, and 25%. The specificities were 50, 45, 48,
      and 79%, respectively. The sensitivities and specificities of different invasive
      techniques are much lower than those reported in clinical studies.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8306026
TI  - Abnormal lipid composition of bronchoalveolar lavage fluid obtained from
      individuals with AIDS-related lung disease.
AB  - Surfactant lipids are not only important to the physiologic function of the
      lungs, but may also influence disease processes like Pneumocystis pneumonia, in
      which the interaction of host-defense cells with pathogen occurs within the
      confines of the surfactant-rich alveolar hypophase. In the present studies the
      lipid profile of bronchoalveolar lavage fluid (BALF) was characterized in
      subjects with AIDS-related lung diseases including Pneumocystis pneumonia. BALF
      lipid and total protein measurements were made in 43 subjects with acquired
      immune deficiency syndrome (AIDS)-related lung disease and compared with those
      made in 50 normal human immunodeficiency virus (HIV)-seronegative controls. The
      AIDS patient samples contained significantly greater amounts of total
      cholesterol, phosphatidylglycerol (PG), and protein than the control samples; in
      contrast to previous observations in rodent P. carinii infection, no differences
      were seen in total phospholipid (PL) or phosphatidylcholine (PC) in the two
      groups. The proportions of several of these lipids were deranged in BALF obtained
      from the patient group: PG/PL and PC/cholesterol differed significantly from
      normal samples. In the subset of patients with AIDS-related Pneumocystis
      pneumonia, no correlation was apparent between discrete BALF lipids and clinical
      indices reflective of disease severity. Using these measurements to approximate
      the lipid composition of the alveolar microenvironment in AIDS-related lung
      disease, we performed experiments in which normal human alveolar macrophages were
      exposed to exogenous liposomal lipids and then challenged with P. carinii. The
      ingestion but not binding of P. carinii by macrophages was diminished as a result
      of lipid exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306027
TI  - Proinflammatory cytokines in nasal secretions of allergic subjects after antigen
      challenge.
AB  - To study the role of cytokines in allergic late-phase reactions (LPR), we
      measured cytokines (interleukins [IL]-1 beta, IL-2, IL-4, IL-5, IL-6, and
      granulocyte-macrophage colony-stimulating factor [GM-CSF]) in nasal secretions
      (NS) of eight allergic subjects following antigen or saline provocation. NS were
      collected hourly for 10 h after challenge by a newly developed matrix method. All
      subjects recorded hourly symptom scores. Cytokines were measured using specific
      enzyme-linked immunosorbent assays (ELISA). Compared with prechallenge values,
      significant levels of IL-1 beta were detected in all subjects during the
      immediate reaction (peak, 51.0 +/- 22.4 pg/ml) and LPR (peak, 78.5 +/- 22.6
      pg/ml) after antigen challenges (p < 0.01) but not saline challenges. In
      contrast, GM-CSF and IL-6 showed a delayed rise (peak, 26.4 +/- 1.3 pg/ml and
      33.8 +/- 10.0 pg/ml, respectively) at hour 4 in the antigen-challenge period (p <
      0.01 versus saline). NS from 4 donors also showed detectable IL-5 (7.6 to 155
      pg/ml) during the immediate reaction and LPR after allergen challenges (versus
      saline, p < 0.01). The levels of cytokine correlated (p < 0.05) with
      corresponding total symptom scores during the immediate reaction (IL-1 beta) and
      LPR (IL-1 beta, GM-CSF, and IL-6). IL-2 and IL-4 were not detected in any sample.
      Thus, IL-1 beta, IL-5, IL-6, and GM-CSF are present in the LPR of allergic
      rhinitis, and their correlation with clinical responses may suggest their role in
      allergic inflammation.

PMID- 8306028
TI  - Immunophenotyping of eosinophils recovered from blood and BAL of allergic
      asthmatics.
AB  - Studies of bronchoalveolar lavage (BAL) fluid from patients with allergic asthma
      have demonstrated active migration of eosinophils into the bronchial lumen after
      allergen challenge. The mechanisms mediating this eosinophil infiltration and
      cell activation are largely unexplained. The expression of several cell-surface
      molecules was measured on eosinophils derived from blood and BAL fluid 4 h after
      an allergen-induced early asthmatic reaction in order to find indications for a
      role of these molecules during extravasation to and activation in the bronchial
      compartment. Nine patients with allergic asthma participated in the study. An
      eosinophil-specific, high-depolarization signal enabled us to measure expression
      on eosinophils in a fluorescence activated cell sorter (FACS) analysis without
      isolation of these cells. Eosinophils recovered from BAL showed a different
      phenotype than blood eosinophils; upregulation of CR-3, p150/95, CD67, and CD63,
      and downregulation of L-selectin indicate that the cells are activated in terms
      of degranulation. Up-regulation of intercellular adhesion molecule-1 (ICAM-1),
      LFA-3, and human leukocyte antigen II (HLA-II) might enable cell-cell contact
      between T-lymphocytes and eosinophils, probably leading to immunomodulation and
      cell activation. The finding that eosinophils in BAL are activated and can
      interact with T cells is further evidence for the proinflammatory role of these
      cells in allergic asthma.

PMID- 8306029
TI  - Bronchoconstriction occurring during exercise in asthmatic subjects.
AB  - To demonstrate physiologic changes associated with asthma symptoms that many
      patients with asthma develop during exercise, we used sustained constant-load and
      interval exercise protocols with subjects breathing dry room temperature air. In
      constant-load exercise, subjects pedaled a stationary bicycle at 50% of their
      maximal power capacity for 36 min. In interval protocols, subjects pedaled at 60%
      of maximal capacity for 6 min and then 40% of maximal for 6 min; the 12-min cycle
      was repeated three times for a total exercise time of 36 min. Maximal expiratory
      flow versus volume maneuvers (MEFV) were obtained before, at 6-min intervals
      during, and at 5-min intervals after exercise. Changes in peak expiratory flow
      (PEF), forced expiratory volume in 1 s (FEV1), and forced expiratory flow at 50%
      of pre-exercise vital capacity (FEF50) were compared with pre-exercise values.
      Within 15 min after a maximal 1-min incremental exercise protocol, mean flows
      decreased compared with pre-exercise (PEF, mean -22%, range -46 to 5%; FEV1, mean
      -21%, range -42 to -3%; FEF50, mean -41%, range -80 to 3%; all p < 0.05). There
      were no significant changes in MEFV flows until 18 min of constant-load exercise,
      when FEV1 and FEF50 fell (FEV1, mean -6%, range -15 to 2%; FEF50, mean -14%,
      range -32 to 6%; both p < 0.05), although changes in PEF were minimal and were
      not significantly different compared with pre-exercise.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8306030
TI  - Prevalence of asthma and atopy in two areas of West and East Germany.
AB  - The German reunification offers a unique opportunity to study the impact of
      environmental factors on the development of childhood respiratory and allergic
      disorders in ethnically similar populations. We investigated the prevalence of
      asthma, hay fever, atopy, and bronchial hyperresponsiveness (BHR) in 9- to 11
      year old children in West Germany (n = 5,030) and East Germany (n = 2,623). A
      self-administered questionnaire was distributed to the parents. Children
      underwent cold air challenge and allergy skin prick tests. Atopic sensitization
      was considerably more frequent in West German children than in their peers in
      East Germany (36.7% versus 18.2%; odds ratio [OR] = 2.6, p < 0.0001). The
      prevalence of current asthma and hay fever was significantly higher in West
      Germany when compared with that in East Germany (5.9% versus 3.9%; OR = 1.5, p <
      0.0001 and 8.6% versus 2.7%; OR = 3.4, p < 0.0001, respectively). Bronchitis,
      however, was more prevalent in East Germany than in the western part of the
      country. The prevalence of BHR as assessed by cold air challenge was higher in
      West Germany compared with that in East Germany (8.3% versus 5.5%, OR = 1.6, p <
      0.001). Logistic regression showed that the West German study area was no longer
      a significant independent determinant of asthma once sensitization to mites,
      cats, and pollen was taken into account. We conclude that sensitization to
      aeroallergens is strikingly more frequent in West Germany than in East Germany
      and this may explain the differences in the prevalence of asthma and hay fever
      between the two parts of the country.

PMID- 8306031
TI  - Passive smoking as a determinant of bronchial responsiveness in children.
AB  - The effect of passive smoking on the degree of nonspecific bronchial
      responsiveness (BR) in children was evaluated. In a cross-sectional survey of
      primary school children (7 to 11 yr) in Latium (Italy), a total of 1,215
      methacholine challenge tests was performed. The children were divided into
      nonresponders (PC20 FEV1 > 64 mg/ml) and responders (PC20 FEV1 < or = 64 mg/ml),
      the latter including a subgroup of strong responders (PC20 FEV1 < or = 4.0
      mg/ml). The role of passive smoking exposure was analyzed through logistic
      regression models. Higher odds ratios were found among girls (for strong
      responders: maternal smoking, OR 2.92; paternal smoking, OR 2.59); moreover,
      among girls there was a dose-response relationship with the number of cigarettes
      smoked by the mother. An effect modification was also detected for father's
      education and household crowding: maternal and paternal smoking were strong
      predictors of bronchial hyperresponsiveness in families in which the head was
      less educated and in overcrowded houses. The results were confirmed using a
      continuous index of BR (slope) and after adjustment for baseline airway caliber.
      We suggest that the effect of parental smoking on children's bronchial
      responsiveness is detectable when the conditions for a higher exposure level at
      home are met; females seem to be more susceptible.

PMID- 8306032
TI  - Quality of life in asthma. I. Internal consistency and validity of the SF-36
      questionnaire.
AB  - Asthma is a chronic disease in which social life is altered. The importance of
      restrictions on social life may be greater in severe asthma or when symptoms are
      not adequately controlled. General scales of quality-of-life (QOL) may be used to
      detect the importance of social life impairment, but it is not yet known whether
      the scores of such QOL measures are reliable and valid in asthmatic patients. A
      study was carried out in 252 patients with asthma of variable severity (FEV1
      ranging from 25 to 131% of predicted) to assess the validity of a general QOL
      scale, the first French version of the SF-36 health status questionnaire (SF-36).
      This is based on 36 items selected to represent nine health concepts (physical,
      social, and role functioning; mental health; health perceptions; energy or
      fatigue; pain; and general health). All nine SF-36 category scores were highly
      significantly correlated with the severity of asthma assessed by the clinical
      score of Aas (p < 0.0007 to p < 0.0001). Eight SF-36 category scores were highly
      significantly correlated with FEV1 (p < 0.003 to p < 0.0001). A high internal
      reliability of SF-36 was found using the alpha coefficient of Cronbach (0.91 for
      the whole questionnaire). The SF-36 questionnaire is valid and reliable in asthma
      and can therefore be used to examine QOL in asthmatic and nonasthmatic patients
      and to determine to what extent asthma impairs social life.

PMID- 8306033
TI  - Predictors of longitudinal change in methacholine airway responsiveness among
      middle-aged and older men: the Normative Aging Study.
AB  - Increasing nonspecific airway responsiveness during aging may precede and
      predispose to the development of asthma in later life. Characteristics
      potentially related to longitudinal change in methacholine airway responsiveness
      were examined over a 3-yr follow-up interval among 435 middle-aged and older men.
      Initial and follow-up evaluation included spirometry, allergy skin testing with
      common aeroallergens, measurement of the serum concentration of total IgE, and
      blood cell counts (total leukocytes and eosinophils, basophils, and neutrophils
      as a percentage of total leukocytes). The initial values and annual rates of
      change of these characteristics were examined by multiple linear regression as
      potential predictors of annual change in methacholine dose-response slope. Annual
      change in basophil count was directly related to change in dose-response slope (p
      = 0.02). Initial values and annual rates of change of other cell counts,
      pulmonary function, allergy skin test reactivity, and serum total IgE
      concentration were not significantly related to change in dose-response slope.
      Cigarette smoking history was also not significantly related to longitudinal
      change in dose-response slope. These data suggest that inflammatory mechanisms
      involving the basophil may be important in the development of increasing
      nonspecific airway responsiveness during aging.

PMID- 8306034
TI  - Human bronchial smooth muscle responsiveness after in vitro exposure to acrolein.
AB  - Human isolated bronchi obtained at thoracotomy from 42 patients were exposed to
      aqueous solutions of acrolein, and the resulting change in contractile responses
      was evaluated by measuring agonist cumulative concentration-response curves
      (CCRC). Contractile responses to carbachol were measured after a variety of
      exposure concentrations, from 0.01 to 3.0 microM, and at times from 5 to 60 min.
      The optimal condition to induce airway smooth muscle hyperresponsiveness was an
      exposure duration of 20 min at a concentration of 0.3 microM. The effect of
      acrolein exposure on human bronchial smooth muscle was also assessed by examining
      the contractile responses to potassium chloride (KCl), histamine, and neurokinin
      A (NKA) in both the absence and the presence of phosphoramidon. Although in vitro
      exposure of the human bronchus to 0.3 microM acrolein did not alter responses to
      KCl, it did increase the efficacy of carbachol and NKA without altering their
      potency. This concentration of acrolein also increased the contractile response
      to low concentrations of histamine and shifted the CCRC to the left. Pretreatment
      with phosphoramidon abolished the differential effect of acrolein on airway
      response to NKA. These results suggest that the mechanism of action of acrolein
      includes inactivation of airway neutral endopeptidase as well as alterations in
      the pharmacomechanical, but not the electromechanical, coupling of human
      bronchial smooth muscle.

PMID- 8306035
TI  - Involvement of tachykinin receptors (NK1 and NK2) in sodium metabisulfite-induced
      airway effects.
AB  - We have investigated the effects of CP-96,345 and SR-48968, new nonpeptide
      (neurokinin) NK1 and NK2 receptor antagonists, respectively, against
      bronchoconstriction and airway microvascular leakage induced by inhaled sodium
      metabisulfite (MBS) in anesthetized guinea pigs. Lung resistance (RL) was
      measured for 6 min after challenge, followed by measurement of extravasation of
      Evans blue dye into airway tissues, used as an index of airway microvascular
      leakage. MBS (80 mM, 30 breaths) caused a significant increase in RL and leakage
      of dye at all airway levels. CP-96,345 (2 mg/kg, intravenous) but not SR-48968
      (1.5 mg/kg, intravenous) significantly inhibited the leakage of dye at all airway
      levels except for trachea. Each antagonist inhibited significantly the maximal
      increase in RL. The combination had a significant additive effect against the
      bronchoconstriction, when compared with SR-48968 alone, and significantly
      inhibited the leakage of dye at the same airway levels as CP-96,345. We conclude
      that bronchoconstriction induced by inhaled MBS is, at least partly, mediated by
      activation of both NK1 and NK2 receptors, and the airway microvascular leakage by
      NK1 receptor stimulation alone.

PMID- 8306036
TI  - Adenosine-induced bronchoconstriction in conscious hyperresponsive and sensitized
      guinea pigs.
AB  - Inhaled adenosine induces bronchoconstriction in asthmatic and allergic subjects
      but not in nonasthmatics. This study examined the responses of conscious guinea
      pigs in which antigen sensitization is induced by ovalbumin pretreatment and
      airway hyperresponsiveness to carbachol is induced by exposure to ozone and
      platelet-activating factor-acether (PAF). Airway responses to aerosol challenge
      with carbachol or adenosine were determined as the change in specific airway
      conductance (SGaw) measured by whole-body plethysmography. In untreated animals,
      carbachol (20 micrograms/ml, 60 s) induced a rapid fall in SGaw (peak, 18 +/- 5%
      at 5 min) indicative of bronchoconstriction, whereas adenosine (1 mg/ml, 60 s)
      caused an increase in SGaw (34 +/- 8% at 15 min). Animals pretreated with
      ovalbumin displayed similar responses to carbachol (14 +/- 5% at 5 min) as
      control animals and were therefore sensitized but not hyperresponsive. However,
      adenosine (1 mg/ml) caused a rapid bronchoconstriction, peaking at 20 min (25 +/-
      5%). Exposure of animals to nebulized PAF-acether (10 micrograms/ml) for 60 s
      produced a bronchoconstriction, which peaked at 10 min (18 +/- 7%) and returned
      to basal levels by 60 min. Similarly, exposure to ozone (1.4 ppm) for 60 min
      caused bronchoconstriction (peak at 20 min, 19 +/- 6%), with recovery after 1 h.
      Both PAF- and ozone-exposed animals displayed significant hyperresponsiveness to
      carbachol administered 1 h from the end of the exposure period. The peak
      bronchoconstrictor responses before and after PAF exposure were 10 +/- 9 and 28
      +/- 4%, and responses before and after ozone exposure were 22 +/- 5 and 61 +/-
      9%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306037
TI  - Airways hyperreactivity and cellular accumulation in a delayed-type
      hypersensitivity reaction in the mouse. Modulation by capsaicin-sensitive nerves.
AB  - The aim of this study was to investigate the possible role of capsaicin-sensitive
      nerves in a pulmonary delayed-type hypersensitivity (DTH) reaction. Mice (Balb/c)
      were skin-sensitized with dinitrofluorobenzene (DNFB; 0.5%, 100 microliters) on
      two consecutive days and challenged intranasally 5 days later with dinitrobenzene
      sulphonic acid (0.6%, 50 microliters). Sensitized mice exhibited tracheal
      hyperreactivity to carbachol 24 and 48 h after challenge; however, no
      hyperreactivity was observed 2 h after challenge. At 24 h, but not at 48 h,
      hyperreactivity was associated with antigen-specific lymphocyte accumulation in
      bronchoalveolar lavage fluid (BALF). Capsaicin pretreatment, resulting in the
      depletion of sensory neuropeptides, virtually abolished hyperreactivity to
      carbachol 24 and 48 h after challenge in sensitized mice. Although at 24 h after
      challenge the lymphocyte population was elevated in the BALF collected from
      capsaicin-pretreated mice, this accumulation was not antigen-specific.
      Additionally, there was an increase in polymorphonuclear leukocyte accumulation
      (neutrophils and eosinophils) in the BALF collected from capsaicin-pretreated
      mice at this time point, but this increase was more profound in the sensitized
      group. In summary, tracheal hyperreactivity and cellular accumulation are
      prominent features of the lymphocyte-associated DTH reaction induced by DNFB in
      the mouse lung. Evidence presented in this report highlights the possible
      importance of sensory neuropeptides in pulmonary inflammation and airways
      hyperreactivity.

PMID- 8306038
TI  - Ventilatory response to exercise in men and women 55 to 86 years of age.
AB  - This study examines the relationship between minute ventilation (VE) and carbon
      dioxide production (VCO2) during exercise in men (n = 128) and women (n = 96), 55
      to 86 yr of age. The means for the slopes of VE-VCO2 (delta VE/delta VCO2),
      examined for graded exercise below the ventilation threshold (TVE), increased
      significantly for men (p < 0.0001), from 25.0 +/- 0.7 (SEM) at mean age 58 (55 to
      59) yr to 32.2 +/- 1.8 at mean age 83 (80 to 86) yr, but did not change for women
      (p = 0.0812), from 22.3 +/- 0.9 at mean age 58 (56-59) yr to 24.2 +/- 2.4 at mean
      age 79 (75 to 85) yr. A correlation that was significantly greater than zero was
      found between delta VE/delta VCO2 and age. The increase in delta VE/delta VCO2
      was 0.29/yr for men (r = 0.47, p < 0.001) and 0.20/yr for women (r = 0.28, p =
      0.0051). In both cases, the explained variance was small (men = 22%; women = 8%).
      VE, tidal volume (VT), and breathing frequency (fb) were examined at VCO2 = 1.0
      L/min, the highest intensity that most older men and women could exercise without
      exceeding TVE. VE was significantly higher by 14% in men 80 to 86 yr of age (38.2
      +/- 1.4 L/min) compared with men 55 to 59 yr of age (33.5 +/- 0.8), whereas there
      were no differences in VE for the women.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306039
TI  - Pulmonary hypertension and hypoxemia in obstructive sleep apnea syndrome.
AB  - To determine whether pulmonary hypertension (PH) can occur in obstructive sleep
      apnea syndrome (OSAS) in the absence of lung or primary cardiac disease, we
      studied 27 patients (26 males, mean age 49 +/- 10 yr) with OSAS (respiratory
      disturbance index [RDI] > 10 events/h) in whom clinically significant lung or
      cardiac diseases were excluded. Pulsed Doppler measurements of pulmonary
      hemodynamics, pulmonary function tests, arterial blood gas analysis, and
      polysomnography were performed. A total of 11 OSAS patients (41%) were found to
      have pulmonary hypertension. The levels of PH were relatively mild (Ppa < or = 26
      mm Hg). There were no differences between PH and non-PH patients in body mass
      index (BMI), smoking history, or lung function. PH patients were more hypoxemic
      when awake than non-PH patients (PaO2 = 72.2 +/- 7.6 versus 77.6 +/- 7.3 mm Hg,
      respectively; p < 0.05) but did not differ in severity of sleep apnea (RDI = 51.9
      +/- 25.1 versus 56.8 +/- 26.2 events/h, respectively; p = NS) or indices of sleep
      desaturation. The hypoxemia in PH patients could not be explained by impairment
      of lung function, greater body mass, or a higher prevalence of smoking, and PaO2
      in the study population was significantly correlated with Ppa (r = -0.46, p <
      0.02) but not with FEV1 or BMI. We conclude that lung disease is not a
      prerequisite for PH in OSAS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306040
TI  - Pulmonary vascular abnormalities and ventilation-perfusion relationships in mild
      chronic obstructive pulmonary disease.
AB  - Morphologic changes in pulmonary muscular arteries may modify the mechanisms that
      regulate the pulmonary vascular tone and contribute to maintaining an adequate
      ventilation-perfusion (VA/Q) matching in patients with chronic obstructive
      pulmonary disease (COPD). To analyze the relationships between the abnormalities
      of pulmonary muscular arteries and the degree of VA/Q inequality, and to assess
      the effect of these abnormalities on the changes in VA/Q relationships induced by
      oxygen breathing, we studied a group of patients with mild COPD undergoing
      resective lung surgery. According to the degree of airflow obstruction and the
      increase in VA/Q mismatch produced by 100% O2 breathing (delta logSD Q), patients
      were divided into three groups: (A) patients with normal lung function, (B)
      patients with airflow obstruction and a high response to oxygen (delta logSD Q >
      0.4), and (C) patients with airflow obstruction and a low response to oxygen
      (delta logSD Q < 0.4). Pulmonary arteries in Groups B and C showed narrower
      lumens and thicker walls than in Group A. These morphologic changes were produced
      mainly by an enlargement of the intimal layer and were more pronounced in Group C
      than in Group B. The assessment of intimal area as a function of artery diameter
      showed that the increase in intima in Group C took place predominantly in
      arteries with small diameters (< 500 microns). The mean intimal area on each
      subject correlated with both the PaO2 value (r = -0.46, p < 0.05) and the overall
      index of VA/Q mismatching (r = 0.51, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306041
TI  - Respiratory muscle strength in the elderly. Correlates and reference values.
      Cardiovascular Health Study Research Group.
AB  - Maximal inspiratory pressure (MIP) was assessed in 4,443 ambulatory participants
      of the Cardiovascular Health Study, 65 yr of age and older, sampled from four
      communities. Maximal expiratory pressure (MEP) was also measured in 790
      participants from a single clinic. Positive predictors of MIP included male sex,
      FVC, handgrip strength, and higher levels of lean body mass (or low bioelectric
      resistance). Negative predictors were age, current smoking, self-reported fair to
      poor general health, and waist size. Both participant and technician learning
      effects were noted, but there was no independent effect of race, hypertension,
      cardiovascular disease, or diabetes. A healthy subgroup was identified by
      excluding current smokers, those with fair to poor general health, or an FEV1
      less than 65% of predicted. Mean values determined from the healthy group were
      57/116 cm H2O (MIP/MEP) for women, and 83/174 for men. Lower limits of the normal
      range (fifth percentiles) were 45 to 60% of the mean predicted values. The
      reference equations derived from this group of healthy 65 to 85-yr-olds may be
      used by pulmonary function laboratories and respiratory therapists who evaluate
      the respiratory muscle strength of elderly patients.

PMID- 8306042
TI  - Sources of variation in FEV1.
AB  - The American Thoracic Society (ATS) recommendations to establish reproducibility
      of the forced expiratory volume in one second (FEV1) are that the value come from
      "at least 3 acceptable forced expiratory curves" where "the largest forced vital
      capacity maneuver (FVC) and the second largest FVC should not vary by more than
      5%." It has been suggested that there is a "negative effort dependence" of the
      FEV1 and, alternatively, that the magnitude of the FVC influences the FEV1. We
      examined the relationship between FEV1 and a direct measurement of effort, or
      work, defined as the area under the alveolar pressure-volume curve in 1 s.
      Thirteen normal individuals and 17 patients with cystic fibrosis or asthma were
      instructed to make a series of maximal efforts, as in routine testing. Comparing
      the maneuver that resulted in the greatest work to that with the lowest work, all
      with FVCs within 5% of one another, there was no correlation between change in
      work and change in FEV1 (delta FEV1). There was a significant relationship
      between delta FEV1 and changes in FVC (r = 0.49, p < 0.01). The delta FEV1 did
      not correlate with the degree of hyperinflation (the FRC) or degree of airflow
      limitation (the initial FEV1). The magnitude of changes in FEV1 was small and
      almost always within acceptable limits for reproducibility. Because a larger FVC
      is due either to an increased inspiration, which could affect the FEV1, or to an
      increased expiratory reserve volume, which occurs only after the first second,
      these results emphasize the importance of a maximal inspiration at the start of
      the test.

PMID- 8306043
TI  - Determinants of progression in idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive form of lung disease with a
      median survival of less than 5 yr. To address the progressive nature of this
      disease process, we investigated the determinants of decrements in lung function
      in patients with IPF. We prospectively evaluated 39 subjects with IPF. Our study
      subjects were followed for an average of 2 yr (range, 49 to 1,883 days) and lung
      function was measured on at least two separate occasions (mean = 9.1 separate
      tests) during the follow-up period. Since IPF is characterized by reduced lung
      volume and abnormal gas exchange, our analysis focused on the determinants of
      total lung capacity (TLC) and diffusing capacity of carbon monoxide (DLCO) during
      the period of observation. Although, on average, there was a 5.3% increase in the
      TLC and a 9.8% increase in DLCO between the first and last measure of lung
      function, 25% of the study population experienced a decline in the TLC and 28% of
      the study population experienced a decline in the DLCO. Decrements in TLC were
      independently associated with severe dyspnea (p = 0.01) and treatment with
      cyclophosphamide (p = 0.03). Decrements in DLCO were significantly and
      independently associated with more pack-years of cigarette smoking (p = 0.02),
      moderate (p = 0.03) or severe (p = 0.02) dyspnea, and treatment with
      cyclophosphamide (p = 0.0002). These findings indicate that several clinical
      characteristics are independently associated with subsequent declines in TLC and
      DLCO in patients with IPF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306044
TI  - Determinants of survival in idiopathic pulmonary fibrosis.
AB  - To identify the determinants of survival in patients with idiopathic pulmonary
      fibrosis (IPF), we performed a survival analysis on 74 subjects with IPF. The
      study subjects were on average 64 yr of age (range, 25 to 83 yr), 62% were male,
      and 29% were never smokers. A tissue diagnosis was made in 67 (91%) of our study
      subjects. These subjects were followed for a mean period of 4 yr (range, 1.4 to
      118.8 months) after the onset of pulmonary symptoms. During the period of
      observation, 41 subjects died (median survival = 28.2 months) and 33 continue to
      survive (median follow-up period = 60.9 months). A univariate analysis
      demonstrated that diminished survival was significantly associated with male
      gender (hazard ratio = 1.98; 95% confidence interval [CI] = 1.01-3.85), a higher
      FEV1/FVC ratio (hazard ratio = 1.82 [per 10% increase in the FEV1/FVC ratio]; 95%
      CI = 1.21-2.73), a lower percent predicted FVC (hazard ratio = 0.74; 95% CI =
      0.60-0.91), a lower percent predicted total lung capacity (TLC) (hazard ratio =
      0.75; 95% CI = 0.60-0.94), a lower percent predicted diffusing capacity of carbon
      monoxide (DLCO) (hazard ratio = 0.69; 95% CI = 0.53-0.89), a higher ILO profusion
      category on chest radiograph (hazard ratio = 3.52; 95% CI = 1.58-7.87), and an
      enhanced release of prostaglandin E2 (PGE2) by cultured alveolar macrophages
      (hazard ratio = 1.32 [per 10 pm/ml of PGE2]; 95% CI = 1.07-1.62).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8306045
TI  - The motility of lung lymphocytes in hypersensitivity pneumonitis and sarcoidosis.
AB  - Lymphocytes obtained by bronchoalveolar lavage (BAL) in hypersensitivity
      pneumonitis (HP) and pulmonary sarcoidosis (PS) are believed to be derived from
      interstitial inflammatory lesions of the lung in which lymphocytes have migrated
      from the blood. Because cellular motility is one of the important factors in
      lymphocyte migration, we investigated the motility of BAL lymphocytes from 12
      patients with HP and 12 with PS, as well as their responsiveness to
      chemoattractants in vitro by modified Boyden chamber method. Motility was
      evaluated by the number of migrated cells and the migration distance. The numbers
      of migrated BAL lymphocytes from patients with HP and PS in albumin-containing
      medium were 318.3 +/- 93.0 (mean +/- SD) and 207.6 +/- 35.5, respectively, and
      were greater than those of BAL lymphocytes from normal control subjects (133.3 +/
      40.9) and blood lymphocytes, and comparable with those of mitogen-activated
      blood lymphocytes. The motility of BAL lymphocytes in these diseases compared
      with blood lymphocytes was also increased in protein-free medium. In addition,
      the culture supernatants of alveolar macrophages (AM) enhanced the motility of
      BAL, mitogen-activated, and blood lymphocytes. These results suggest that BAL
      lymphocytes in these diseases are functionally motile, and their enhanced
      motility, as well as mediators from AM, may facilitate the accumulation of
      lymphocytes at the epithelial surface.

PMID- 8306046
TI  - Bronchoalveolar lavage cytology and immunocytology in pulmonary tuberculosis.
AB  - Limited data on the cellular and immunocytologic characteristics of
      bronchoalveolar lavage (BAL) fluid in pulmonary tuberculosis have been reported.
      We therefore studied 40 patients with active disease. BAL fluid differential cell
      counts and lymphocyte subsets were determined. The findings were compared with
      data from 47 patients with active sarcoidosis and 30 healthy control subjects.
      The proportion of lymphocytes was increased in both diseases (p < 0.001 versus
      control subjects) but with no difference compared to one another. The CD4/CD8
      ratio was normal in 33 of 40 patients with pulmonary tuberculosis in contrast to
      sarcoidosis, with an increased ratio in 33 of 47 patients. HLA-DR+ T lymphocytes
      were significantly increased in both pulmonary tuberculosis and sarcoidosis (p <
      0.05 versus control group). The proportion of CD57+ lymphocytes was normal in all
      study groups. We conclude that pulmonary tuberculosis and sarcoidosis are
      characterized by an increased percentage of lymphocytes in BAL fluid with a
      similar proportion of activated T cells. In contrast to active sarcoidosis, in
      which an elevated CD4/CD8 ratio is characteristic, in the majority of pulmonary
      tuberculosis patients the CD4/CD8 ratio is within the normal range.

PMID- 8306047
TI  - Neutrophil formyl-peptide receptors. Relationship to peptide-induced responses
      and emphysema.
AB  - A reproducible assay was established to assess the number of formyl-peptide
      receptors expressed on the surface of human polymorphonuclear leukocytes (PMN).
      Using this assay the number of receptors was shown to demonstrate wide within-
      and between-subject variability. However, the receptor numbers were related to
      the chemotactic response (r = 0.572) and degranulation response (r = 0.512) to
      the peptide formyl-methionyl-leucyl-phenylalanine. Subsequent studies showed
      increased receptor numbers on PMN from patients with emphysema (median, 459 x
      10(3)/cell; range, 207 to 1,080) as compared with age-matched control subjects
      (median, 288; range, 168 to 519; p < 0.02), which may explain the increased
      chemotactic response of the PMN to formyl peptides. This difference was not
      observed in patients with bronchiectasis, suggesting that the increased receptor
      number is a feature of emphysema. Furthermore, the increase was largely a feature
      of smokers with emphysema (median, 463; range, 362 to 1,080), whereas age-matched
      smokers without emphysema had lower numbers of receptors (p < 0.001; median, 332;
      range, 243 to 411). This observation suggests a mechanism that may explain the
      susceptibility of some smokers to the development of emphysema.

PMID- 8306048
TI  - Surgical resection of pulmonary metastases. Up to what number?
AB  - Specific results on the surgical resection of a large number of pulmonary
      metastases (PM) are currently unavailable, and the risk-benefit ratio of this
      aggressive approach may appear questionable. A systematic review of the records
      of 456 adult patients who underwent thoracic surgery for PM between 1979 and 1990
      led to the identification of 44 patients who underwent at least one resection of
      eight or more PM (range eight to 110), of whom 33 (75%) had PM from osteogenic or
      soft tissue sarcoma. These 44 patients underwent a total of 77 operations, of
      which 47 (61%) were bilateral and nine (12%) incomplete resections. The 3- and 5
      yr probabilities of survival after the first resection of eight or more PM were
      36 and 28%, respectively, and were not significantly different from those of the
      412 other patients who underwent surgery for PM over the same period. In this
      small group of patients, only the quality of resection (complete or incomplete)
      was found to be a highly significant prognostic factor (p < 0.01). A critical
      analysis of the reported data supports the view that, at least in patients with
      osteogenic or soft tissue sarcoma, the prognostic value of the number of PM seems
      to be more dependent on associated resectability than on the number per se and
      that, after careful preoperative patient selection, PM that can be resected
      should be resected, whatever their number.

PMID- 8306049
TI  - Repeatability of measurements of normal lung sounds.
AB  - The stability of lung sounds measurements over time may influence their clinical
      usefulness. In the present study we investigated the temporal variability of the
      spectral pattern of normal lung sounds. Breath sounds from five healthy men were
      recorded on the trachea and at four locations over the chest wall. Each subject
      was studied twice with a time interval of 1 wk. On each occasion, measurements
      were done in duplicate, with a 30-min interval between recordings. Sounds were
      amplified, band-pass filtered (75 to 2,000 Hz) and digitized into a computer, and
      the average spectra of the inspiratory, expiratory, and background sounds were
      calculated. The variability of corresponding spectra were calculated between the
      daily duplicate (same-day variability, SDV) and between the two recording
      sessions (between-day variability, BDV). SDV was 32.8 +/- 12.0% during
      inspiration and 40.8 +/- 12.6% during expiration (p = 0.005). BDV was 36.9 +/-
      11.3% during inspiration and 42.7 +/- 12.7% during expiration. These values were
      not significantly different from SDV except for sounds recorded from the
      interscapular region (SR). At this location the SDV was 28.2 +/- 7.2% during
      inspiration and 40.8 +/- 14.2% during expiration, and the BDV was 48.2 +/- 18.7%
      during inspiration and 77.6 +/- 22.3% during expiration (p < 0.05). The increased
      BDV at SR was found to be a result of slight differences in microphone position
      from the first session to the next. Similar changes in microphone position at the
      other recording sites did not alter the variability of lung sounds.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8306050
TI  - Airway inflammation in nonasthmatic subjects with chronic cough.
AB  - The physiopathology of chronic cough remains obscure. We evaluated the
      possibility that chronic cough in nonasthmatic subjects is associated with airway
      inflammation, and if this is so, what the relationship between this inflammation
      and the possible etiology of cough might be, as well as its response to inhaled
      steroids. Nineteen nonsmoking, nonasthmatic subjects referred for a persistent
      cough (mean: 3.8 yr) were evaluated and compared with 10 normal subjects. The
      evaluation included a respiratory questionnaire, a physical examination, allergy
      skin-prick tests, chest and sinus radiographs, esophageal pH monitoring,
      measurements of expiratory flows, methacholine and citric acid challenges, and
      flexible bronchoscopy for bronchoalveolar lavage (BAL) and bronchial biopsies.
      Fourteen subjects further accepted participation in a randomized, double-blind
      crossover trial of inhaled beclomethasone (500 micrograms four times daily) and a
      placebo for 1 mo each. Four groups of subjects were identified according to the
      presence of postnasal discharge (n = 4), gastroesophageal reflux (n = 6), both
      conditions (n = 5), or neither (n = 4). Subjects with chronic cough had an
      increased number of inflammatory cells in their bronchoalveolar lavage fluid
      (BALF), but there was no significant difference between the four subgroups of
      coughers. As compared with control subjects, the bronchial biopsies of subjects
      with chronic cough showed increased epithelial desquamation (p = 0.004) and
      inflammatory cells (p = 0.005), particularly mononuclear cells (p < 0.01), in
      addition to submucosal fibrosis, squamous-cell metaplasia, and loss of cilia.
      These findings were not significantly different between the different etiologic
      groups. In subjects with chronic cough, basement-membrane thickness was normal
      and not different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306051
TI  - Long-term viral enhancement of lung response to Saccharopolyspora rectivirgula.
AB  - The current study was done to look at the long-term enhancing effect of a single
      viral infection on repeated Saccharopolyspora rectivirgula (SR) antigenic
      challenges in mice and at inflammatory cytokines in this enhancement. Four groups
      of C57BI/6 mice were studied: Group 1 received intranasal instillations of
      saline, 3 days per week; Group 2, intranasal instillations of saline plus one
      intranasal instillation of 80 hemagglutination units (HAU) of Sendai virus after
      3 wk of saline; Group 3, instillations of SR, 3 days per week; and Group 4,
      instillations of SR, 3 days per week, plus one instillation of Sendai virus after
      3 wk of SR. Bronchoalveolar lavages (BAL) were performed 15 and 30 wk after the
      virus inoculation in the appropriate groups. Each time, a two- to threefold
      increase in BAL cell counts was obtained from virus-infected animals challenged
      with SR compared with animals that received the SR alone. Animals infected with
      virus only showed values similar to those of control animals. A higher percentage
      of large foamy multinucleated cells were found in the BAL from the SR+Sendai
      group than the SR alone group (7.92 +/- 0.730% compared with 1.8 +/- 0.296%).
      These cells were not seen in the other groups. BAL levels of TNF-alpha and IL-1
      alpha at 15 wk were much higher in SR+Sendai-treated (1,439 +/- 268 and 96 +/- 9
      pg/ml, respectively) than SR alone-treated animals (361 +/- 100 and 23 +/- 4
      pg/ml). BAL fluid of control animals and Sendai alone animals contained 64 +/- 24
      and 65 +/- 15 pg/ml of TNF-alpha, but no IL-1 alpha was detected.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8306052
TI  - Evaluation of human cytomegalovirus latency in alveolar macrophages.
AB  - Cytomegalovirus (CMV) pneumonia is a major cause of illness in immunocompromised
      patients. The sites of human CMV (HCMV) latency are still not clearly defined.
      The present study was therefore designed to investigate the hypothesis that
      alveolar macrophages could constitute such a site. DNA extracted from alveolar
      cells collected by bronchoalveolar lavage and blood mononuclear cells (BMC) from
      asymptomatic nonimmunocompromised CMV-seropositive and CMV-seronegative patients
      were investigated. Controls consisted of DNA from a CMV-infected MRC5 cell line,
      BMC and alveolar macrophages from patients with acute CMV infection. Polymerase
      chain reaction (PCR) was designed for detection of a 290-bp fragment of the
      promoter region of the major immediate early gene of HCMV conserved within the
      various HCMV strains and without homology with the human genome. The limit of
      detection of the method was evaluated to be one HCMV viral copy per 10(4) cells.
      HCMV DNA was detected in BMC or alveolar cells of all patients with acute CMV
      infection. In contrast, no HCMV DNA was detected in alveolar cells and BMC from
      nonimmunocompromised asymptomatic HCMV-seropositive patients. In conclusion, in
      the present experiment, no latent HCMV could be detected in alveolar cells
      collected in nonimmunocompromised asymptomatic CMV-seropositive patients.

PMID- 8306053
TI  - Development of pulmonary infection in mice inoculated with Blastomyces
      dermatitidis conidia.
AB  - Intratracheal injection of Balb/cByJ mice with 10(4) Blastomyces dermatitidis
      conida produces chronic pulmonary and disseminated blastomycosis characterized by
      pyogranulomatous inflammation. To study the evolution of the pulmonary infection,
      mice were killed at varying intervals after inoculation, their lungs cultured and
      examined histologically. Nodular intraalveolar infiltrates of macrophages (M phi)
      were seen on Day 1 with occasional admixed polymorphonuclear leukocytes (PMN).
      Phagocytized yeast forms within M phi were evident by Day 5. By Day 28
      pyogranulomas, which developed first as central microabscesses associated with a
      peripheral zone of M phi and giant cells containing internalized yeast, were a
      prominent feature of the infection. Lymphocytic and plasmacytic infiltrates,
      accumulating next to granulomas, formed the major peripheral component of the
      granuloma by Day 35. Formation of pyogranulomas was coincident with the host's
      failure to contain fungal growth measured by the sharp rise in colony-forming
      units recovered from lungs. Antibody against B. dermatitidis was first detected
      at Day 35 by enzyme immunoassay, but not until Day 63 by double immunodiffusion.
      During the 4 wk after inoculation, pulmonary lavage fluid contained > 90% M phi
      and < 3% PMN. On day 28, PMN rose to 17%, reaching 40% on Day 42. These data
      contribute to our knowledge of this model and help form the basis for
      investigations into the roles of fungal pathogenic and host defense mechanisms in
      blastomycosis.

PMID- 8306054
TI  - Extravascular coagulation and fibrinolysis in murine lung inflammation induced by
      the mycobacterial cord factor trehalose-6,6'-dimycolate.
AB  - Diffuse pulmonary inflammation in interstitial lung diseases is associated with
      increased coagulation in the extravascular spaces of the lung. We hypothesized
      that conditions favoring coagulation over fibrinolysis in the lung are related to
      inflammation. Pulmonary coagulation and fibrinolysis were studied in two strains
      of mice susceptible or resistant to the development of lung inflammation in
      response to the mycobacterial cell wall glycolipid trehalose-6,6'-dimycolate
      (TDM). Susceptible animals treated with TDM intravenously develop well-organized
      collections of mononuclear cells in the lung parenchyma referred to as granulomas
      in this report. More granulomas were found in the susceptible ICR mice than in
      the resistant A/J mice after intravenous administration of TDM (7 +/- 1
      granulomas/mm2 versus 1 +/- 0.3 granulomas/mm2, p = 0.005). Granuloma formation
      was associated with increased lung procoagulant activity (PCA) measured in
      bronchoalveolar lavage (BAL) cell lysates from susceptible mice. In contrast, TDM
      resistant A/J mice challenged with TDM did not have a significant BAL cell PCA
      response, but expressed several-fold greater levels of lung BAL fluid plasminogen
      activator activity (PAA) than ICR mice. To examine the role of coagulation in the
      TDM pulmonary inflammatory response, susceptible C57Bl/10SnJ mice were
      anticoagulated by oral administration of warfarin prior to challenge of TDM;
      these mice developed fewer pulmonary granulomas than TDM-treated mice without
      warfarin treatment (2.6 +/- 0.5 granulomas/mm2 versus 6.5 +/- 0.8 granulomas/mm2,
      p < 0.001) but had similar BAL cell PCA and lung inflammatory changes as measured
      by lung weights and BAL cellularity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306055
TI  - Oxidative epithelial damage produces hyperresponsiveness of human peripheral
      airways.
AB  - The epithelium probably modulates airway smooth muscle responsiveness by
      producing relaxing factors, by inactivating agonists, or by acting as a physical
      barrier. In isolated airway strips, however, only a limited modulatory role of
      the epithelium has been found, and this may well be due to shortcomings of this
      airway model. The present study compares the modulatory role of the airway
      epithelium in human airway tubes and strips. In addition, since oxygen radicals
      may contribute to epithelial damage in asthma, oxidative damage to the airway
      epithelium was induced with luminally applied hydrogen peroxide (H2O2), and
      changes in responsiveness to the agonists histamine, methacholine, and salbutamol
      were measured. To examine whether intact epithelium acts as a barrier to
      histamine, the histamine concentration in the organ bath was measured in tubes
      with intact and damaged epithelium stimulated from the mucosal side. In airway
      strips, no differences in responsiveness were found between intact and epithelium
      denuded airways for any of the three agonists. In contrast, the sensitivity of
      airway tubes to both histamine and methacholine was significantly lower with
      mucosal stimulation than with serosal stimulation (-log EC50: 4.87 and 4.92
      versus 5.87 and 5.45 for histamine and methacholine, respectively, p < 0.001). No
      difference was found between the sensitivity to salbutamol of mucosally and
      serosally stimulated airways (-log EC50: 6.19 and 6.20, respectively). The
      modulation of the sensitivity to contractile agonists by the epithelium increased
      with increasing airway size, and was abolished after treatment with
      H2O2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306056
TI  - Establishing diagnosis of pulmonary malignant lymphoma by gene rearrangement
      analysis of lymphocytes in bronchoalveolar lavage fluid.
AB  - We report the successful application of gene rearrangement analysis to the
      lymphocytes obtained by bronchoalveolar lavage (BAL) for the diagnosis of
      pulmonary malignant lymphoma. A 45-yr-old female patient who had been suffering
      from back pain was shown to have macroglobulinemia and pulmonary infiltrative
      shadow by chest radiography. Transbronchial lung biopsy revealed a small B-cell
      infiltrate with monotypic immunoglobulin expression (IgM/kappa light chain), and
      malignant lymphoma was highly suspected. BAL was performed to evaluate the cell
      profiles. The phenotyping of lavaged lymphocytes by flow cytometry revealed that
      the major component of the lymphocytes was CD3-positive T cells, and that CD21
      positive B cells accounted for only 10% of all lymphocytes. This result was
      contradictory to the immunohistochemical population of lymphocytes in biopsied
      specimens. However, gene analysis of lavaged lymphocytes revealed positive
      immunoglobulin heavy chain rearrangement and negative immunoglobulin light chain
      and T-cell receptor rearrangement, suggesting that B cells making up a minor
      population of lavaged lymphocytes were proliferating monoclonally. Thus, in this
      case, gene analysis was an effective procedure for detecting the origin of tumor
      cells and distinguishing monoclonality from reactive accumulations. To our
      knowledge, this case represents the first reported application of gene
      rearrangement analysis to cells obtained by BAL. The sensitivity and usefulness
      of this analysis for the accurate evaluation of pulmonary lymphoproliferative
      lesions, when applied to BAL cells, should be emphasized.

PMID- 8306057
TI  - Effect of testosterone administration on upper airway collapsibility during
      sleep.
AB  - Testosterone is thought to play a role in the pathogenesis of obstructive sleep
      apnea (OSA), but the mechanism is unclear. We present a case in which
      testosterone administration induced or exacerbated OSA in a 13-year-old male. We
      demonstrated that exacerbation of OSA by testosterone was associated with an
      increase in upper airway collapsibility during sleep, and that this improved
      after cessation of hormone administration. Our data strongly suggest that the
      mechanism by which testosterone administration may induce or exacerbate OSA is
      through an influence on neuromuscular control of upper airway patency during
      sleep.

PMID- 8306058
TI  - The oxygen delivery/consumption controversy. Approaches to management of the
      critically ill.
AB  - There is no doubt that physiologic dependence of VO2 on DO2 occurs in patients in
      shock. Whether pathologic dependence of VO2 on DO2 occurs in the critically ill
      has not yet been conclusively shown, partly because of the problem of
      mathematical coupling of shared measurement error of cardiac output and arterial
      oxygen content in many studies. In our opinion, contradicting RCTs of increased
      DO2 and the problems encountered in the RCTs to date do not support the practice
      of increasing DO2 to supranormal levels. Finally, we suggest that until
      technology is available to better assess DO2 and VO2 of vital organs and tissues,
      the clinician can negotiate this controversial area in individual patients by
      applying careful clinical assessment and judgement of patient response to changes
      in DO2.

PMID- 8306059
TI  - CT and COPD.

PMID- 8306060
TI  - Collateral ventilation and gas exchange during airway occlusion in the normal
      human lung.

PMID- 8306061
TI  - Quantitation of intraalveolar LF fluid?

PMID- 8306062
TI  - Hugh Blaschko, FRS (1900-1993).

PMID- 8306063
TI  - Thrombolytic effect of a plasminogen-plasminogen activator chimera in a
      photochemically induced thrombosis (PIT) model.
AB  - The thrombolytic effects of the plasminogen/plasminogen activator chimera
      (SUN9216), comprising the fibrin-binding kringle 1 domain of plasminogen and two
      kringle and the serine protease domain of the wild-type tissue plasminogen
      activator (t-PA) including a modification of the mannose glycosylation on the
      kringle 1 of t-PA (PK1 delta FE1X), was compared with tht of t-PA by use of a
      photochemically induced thrombus (PIT) in the rat femoral artery. When SUN9216
      was administered either as an i.v. infusion (1.0 mg kg-1) or as a single bolus
      i.v. injection (1.0 mg kg-1), all parameters were markedly improved compared to t
      PA administered as an i.v. infusion (3.0 mg kg-1). A higher concentration of
      plasminogen activator (PA) activity in plasma was observed after administration
      of SUN9216 which persisted for longer than that after t-PA. It is concluded that
      the thrombolytic effect of SUN9216 is markedly greater than that of t-PA.

PMID- 8306064
TI  - Induction of a glibenclamide-sensitive K-current by modification of a delayed
      rectifier channel in rat portal vein in insulinoma cells.
AB  - In insulinoma cells (RINm5F), the glibenclamide-sensitive K-current (IK(ATP))
      which developed spontaneously or after exposure to levcromakalim or to
      butanedione monoxime was always accompanied by a reduction in the delayed
      rectifier current (IK(V)). At potentials over which IK(V) was fully activated,
      the total outward current remained constant. In rat portal vein, the delayed
      rectifier channel inhibitor, margatoxin, reduced the combined induction of
      IK(ATP) and inhibition of IK(V) by levcromakalim. These data suggest that the ATP
      sensitive K-channel, K(ATP), is a voltage-insensitive state of the delayed
      rectifier, KV.

PMID- 8306065
TI  - Endotoxin-induced arterial endothelial barrier dysfunction assessed by an in
      vitro model.
AB  - Using an in vitro model in which albumin transfer across monolayers of bovine
      aortic endothelial cells (BAEC) was measured, we have shown that
      lipopolysaccharide (LPS) induces a concentration-dependent increase in
      endothelial permeability. This increase was biphasic, having an early peak at 2 h
      and rising again by 24 h. Both peaks were abolished by polymixin B (PMB) but were
      unaffected by N omega-monomethyl-L-arginine, N omega-nitro-L-arginine methyl
      ester or dexamethasone. Furthermore, LPS did not stimulate nitric oxide
      production by BAEC following 24 h exposure. Thus, the LPS-induced increase in
      permeability may account for the vascular leakage of septic shock, but the L
      arginine-nitric oxide system does not appear to be involved.

PMID- 8306066
TI  - Effects of omega-conotoxin on adrenergic, cholinergic and NANC neurotransmission
      in the rabbit urethra and detrusor.
AB  - 1. The effects of omega-conotoxin GVIA (an inhibitor of N-type voltage-operated
      calcium channels; VOCCs) were compared on adrenergic, cholinergic and non
      adrenergic, non-cholinergic (NANC) responses induced by electrical field
      stimulation (EFS) in the rabbit urethra and detrusor. 2. EFS induced a relaxation
      in urethral smooth muscle and lamina propria precontracted by arginine
      vasopressin (AVP). The relaxation was abolished by tetrodotoxin (TTX) or the
      nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine. omega-Conotoxin
      inhibited the relaxation induced by EFS, but not that elicited by the NO donor 3
      morpholino-sydnonimin. The inhibition, however, decreased with increasing
      frequencies of stimulation. Nimodipine, tetramethrin and nickel did not affect
      the omega-contoxin-resistant relaxation in lamina propria, suggesting that
      neuronal L or T VOCCs were not involved in the response. 3. EFS contracted
      urethral smooth muscle at resting tension. The contractions were virtually
      abolished by TTX or prazosin. omega-Conotoxin effectively inhibited the
      contractile responses to EFS, but not those to exogenous noradrenaline. An omega
      conotoxin-resistant contraction was, however, observed at high frequencies of
      stimulation. 4. The detrusor responded with frequency-dependent contractions upon
      EFS. A TTX-resistant contraction less than 10% of controls remained at 30 Hz
      stimulation. At a stimulation frequency of 10 Hz, scopolamine reduced the EFS
      induced contraction by 71%. omega-Conotoxin inhibited the responses in both the
      absence and presence of scopolamine. The inhibition decreased with increasing
      frequencies of stimulation (examined in the absence of scopolamine). omega
      Conotoxin did not affect the contractile responses to carbachol or adenosine 5'
      triphosphate. 5. The adrenergic contraction (25 Hz) and NANC relaxation (10 Hz)
      in the urethra, and cholinergic and NANC contractions (10 Hz) in the detrusor
      were inhibited concentration-dependently by omega-conotoxin.The adrenergic
      contraction in the urethra was 10 times and the cholinergic contraction in the
      detrusor was three times more sensitive to omega-conotoxin than the NANC
      responses.6. These results suggest that NANC neurotransmission is less inhibited
      by omega-conotoxin than transmission mediated by adrenergic and cholinergic
      nerves in the rabbit lower urinary tract. In the urethra a marked omega-conotoxin
      resistant component of the NANC relaxation was observed which increased with
      increasing stimulation frequencies and was unaffected by inhibitors of L and T
      type VOCCs. This raises the question whether VOCCs of a type other than L, T, and
      N is involved in the mediation of this response.

PMID- 8306067
TI  - Solubilization and characterization of GABAB receptor binding sites from porcine
      brain synaptic membranes.
AB  - 1. The characteristics of membrane bound GABAB receptors in pig brain are similar
      to those in rat brain as judged by in vitro binding experiments and sensitivity
      to GTP. The rank order of affinity of GABAB receptor ligands was CGP 54626 > GABA
      approximately (-)-baclofen >> CGP 35348 = CGP 36742 > (+)-baclofen in membranes
      from both species. 2. For solubilization of GABAB receptors from pig brain,
      washed membranes were preincubated with 5 mM MgSO4 and subsequently incubated
      with various detergents. 3-[(3-Cholamidopropyl)dimethyl-ammoniol]-1-propane
      sulphonate (CHAPS) (0.5%) proved to be the most successful, solubilizing 22.7 +/-
      4.7% (mean +/- s.e. mean, n = 6) of GABAB receptors. 3. Binding of [3H]-GABA to
      GABAB receptors solubilized with 0.5% CHAPS exhibited similar characteristics to
      the binding at membrane bound receptors since, firstly, the Kd and Bmax values
      (around 30 nM and 450 fmol mg-1 protein, respectively) were comparable; secondly,
      stereospecific binding for baclofen was obtained in both forms; thirdly, the
      affinity for the agonists GABA and (-)-baclofen and the antagonists CGP 35348,
      CGP 36742 and CGP 54626 were the same; fourthly, comparable sensitivity to Ca2+
      (2.5 mM) was observed and finally, a similar sensitivity to GTP was apparent. 4.
      Saturation experiments performed with the GABAB antagonist, [3H]-CGP 54626,
      indicated a higher Kd value and a lower Bmax value for solubilized (7.7 +/- 2.6
      nM and 1033 +/- 41 fmol mg-1 protein, mean +/- s.e. mean, n = 3) than for
      membrane bound receptors (1.35 +/- 0.08 nM, 1171 +/- 20 fmol mg-1 protein, n =
      3).

PMID- 8306068
TI  - Action of purine and pyrimidine nucleotides on the rat superior cervical
      ganglion.
AB  - 1. Using a grease-gap technique, we have investigated the effects of purine and
      pyrimidine nucleotides on the d.c. potential of the rat isolated superior
      cervical ganglion (SCG). 2. Of the purines tested, adenosine, adenosine 5'
      triphosphate (ATP), beta,gamma-methylene-adenosine 5'-triphosphate (beta,gamma
      MeATP) at up to 300 microM produced concentration-dependent hyperpolarizations,
      whereas 2-methyl-thio-ATP (2-Me.S.ATP) and alpha,beta-methylene-ATP (alpha,beta
      MeATP) depolarized ganglia. Of the pyrimidines tested, uridine 5'-triphosphate
      (UTP) produced concentration-dependent depolarizations and cytosine 5'
      triphosphate (CTP) at 1000 microM produced considerably smaller but significant
      depolarizations. In contrast uridine 5'-monophosphate (UMP) at 1000 microM
      hyperpolarized ganglia. The relative order of potency of purines and pyrimidines
      to depolarize ganglia was: UTP > alpha,beta-MeATP >> CTP > 2-Me.S.ATP and to
      hyperpolarize ganglia was: adenosine = beta,gamma-MeATP > ATP > UMP. 3. The
      ability of purines and pyrimidines to alter the depolarizing response caused by
      muscarine and of purines to alter depolarization induced by gamma-aminobutyric
      acid (GABA) was determined. The relative order of potency of nucleotides in
      depressing submaximal depolarization caused by muscarine (100 nM) was: adenosine
      = ATP > beta,gamma-MeATP whereas 2-Me.S.ATP, alpha,beta-MeATP and UTP did not
      significantly alter depolarization caused by muscarine. At 100 microM beta,gamma
      MeATP and adenosine but not ATP potentiated GABA-induced depolarizations. 4.
      Hyperpolarizations caused by adenosine, ATP, beta,gamma-MeATP and UMP and
      depolarizations caused by alpha,beta-MeATP were enhanced in medium containing
      reduced concentrations of calcium (0.1 mM) and potassium (2 mM). In this medium 8
      phenyltheophylline abolished hyperpolarizations caused by adenosine and reversed
      hyperpolarizations caused by ATP into depolarizations. Suramin (300 microM), a P2
      purinoceptor antagonist, significantly reduced the depolarizing response caused
      by alpha,beta-MeATP and significantly increased hyperpolarizations caused by ATP
      and Beta,gamma-MeATP. Suramin (300 microM) did not significantly alter
      depolarizations caused by l,l-dimethyl-4-phenylpiperazinium (10 microM),
      potassium(3 mM) or muscarine (100 nM) and significantly potentiated
      depolarizations caused by UTP (100 microM).5.It is concluded that the rat SCG
      contains PI-purinoceptors that hyperpolarize the ganglion and diminish
      sensitivity to muscarine, and P2X-purinoceptors that depolarize the SCG. There is
      also some evidence to suggest the presence of receptors for UTP, i.e.,
      pyrimidinoceptors, which depolarize SCG neurones.

PMID- 8306069
TI  - Increases in intracellular calcium via activation of an endogenous P2
      purinoceptor in cultured CHO-K1 cells.
AB  - 1. Increases in intracellular calcium ([Ca2+]i) were measured in chinese hamster
      cultured ovary cells (clone, CHO-K1), by use of the fluorescent, calcium
      sensitive dye, fura-2. 2. Addition of both ATP and UTP elicited rapid increases
      in [Ca2+]i due to mobilization from intracellular stores and calcium entry across
      the plasma membrane. 3. Omission of calcium from the extracellular medium and pre
      incubation with the inorganic calcium channel blocker, nickel (Ni2+) prevented
      the calcium entry components of the responses. 4. Investigation of the
      concentration-response relationships of various analogues of ATP suggests the
      presence of a purinoceptor which cannot be characterized as P2X or P2Y. In
      addition, there appears to be a sub-population of P2Y-purinoceptors which do not
      cross-react with the 'nucleotide' receptor population. 5. Cross-desensitization
      and additivity experiments suggest that both ATP and UTP activate the same
      receptor. 6. Pre-incubation with the tumour-promoting agent, beta-phorbol-12,13
      dibutyrate (PDBu), caused a reduction in the increases in [Ca2+]i, suggesting a
      role for protein kinase C in feedback inhibition of purinoceptor responses in
      this cell line. 7. In summary, we present evidence for the existence of an
      endogenous P2U-purinoceptor (or 'nucleotide receptor') which is linked to
      increases in [Ca2+]i in CHO-K1 cells.

PMID- 8306070
TI  - The action of Hoe 140 on the bradykinin-induced splenic pressor reflex of the
      anaesthetized cat.
AB  - 1. Intrasplenic injection of bradykinin (BK) induced a dose-dependent pressor
      response in the anaesthetized cat, with an ED50 of 0.98 +/- 0.43 nmol. In
      contrast, intrasplenic administration of desArg9bradykinin (desArg9BK) was
      without significant effect at doses of up to 200 nmol. 2. Intravenously
      administered BK induced a dose-dependent depressor response in the anaesthetized
      cat, with an ED50 of 0.86 +/- 0.09 nmol kg-1. desArg9BK was again without
      significant effect in this system at doses of up to 200 nmol kg-1. 3. Both the
      pressor and depressor responses to BK were antagonized to a similar degree in a
      dose-dependent manner by Hoe 140 (10 and 100 nmol kg-1, i.v.). 4. At these doses,
      Hoe 140 appears to be a specific BK antagonist as it was ineffective against
      pressor responses to intrasplenic injection of capsaicin (5 nmol), while blocking
      those to an approximately equieffective dose of BK (1 nmol) in a dose-dependent
      fashion. 5. Both the pressor response to intrasplenic BK and the depressor
      response to intravenous BK in the anaesthetized cat appear to be mediated by B2
      receptors. This model may be useful in the quantitative determination of the
      antinociceptive potency of BK antagonists.

PMID- 8306071
TI  - Endothelium-dependent noradrenaline-induced relaxation of rat isolated cerebral
      arteries: pharmacological characterization of receptor subtypes involved.
AB  - 1. The endothelium-dependence of catecholamine-induced relaxation of rat cerebral
      arteries was investigated in vitro. 2. In the basilar artery (BA), the maximal
      relaxant response was most pronounced with noradrenaline (NA), less with
      isoprenaline (Iso), and only very little with terbutaline. Methoxamine and the
      alpha 2-adrenoceptor selective agonists BHT 933 and clonidine, had no relaxant
      effect. 3. In BA, the relaxation by NA or Iso was markedly attenuated by N omega
      nitro-L-arginine (L-NOARG) 10(-4) M. Short term perfusion of the vessels by
      Triton X 100 (1:1,000) suppressed the NA-induced relaxation. 4. The relaxation
      induced by NA or Iso was markedly reduced in presence of L-NOARG in the
      posterior, medial and anterior cerebral artery. 5. In BA, NA-induced relaxation
      was non-competitively inhibited by propranolol, atenolol, and the beta 1- and
      beta 2-adrenoceptor selective antagonists, CGP 20712 A and ICI 118551. 6. The
      relaxant NA-effect was not affected by prazosin but was non-competitively blocked
      by phentolamine. 7. The Iso-induced relaxation was competitively blocked by
      propranolol, whereas atenolol, CGP 20712 A and ICI 118551 caused a non
      competitive inhibition. 8. The experiments indicate that the catecholamine
      induced relaxation in rat isolated cerebral arteries depends upon the
      endothelium. They suggest that the NA-induced relaxation of BA is mediated by
      different alpha- and beta-adrenoceptors and that the Iso-induced relaxation is
      mediated by different beta-receptors. The findings would also be compatible with
      the idea of a receptor type which cannot be characterized by the pharmacological
      tools that we have used.

PMID- 8306072
TI  - Nasal administration of an ACTH(4-9) peptide analogue with dimethyl-beta
      cyclodextrin as an absorption enhancer: pharmacokinetics and dynamics.
AB  - 1. The systemic absorption and the neurotrophic effect of the metabolically
      stabilized ACTH (4-9) analogue, Org2766, were investigated following intranasal
      (i.n.) administration. 2. Without additives the nasal bioavailability of the
      peptide was in the order of 15 and 10% in rats and rabbits, respectively. The
      absorption could be improved by addition of a variety of absorption enhancers to
      the nasal preparation. The beta-cyclodextrin derivative, dimethyl-beta
      cyclodextrin (DM beta CD) at a concentration of 5% (w/v) improved the absorption
      in rats about 5 fold from 13 +/- 4% (mean +/- s.d.) for administration of the
      peptide alone to 65 +/- 21%, and in rabbits 1 to 2 fold, from 10 +/- 6% to 17 +/-
      8%. 3. The increased permeability of the rat nasal mucosa for Org2766 caused by
      DM beta CD in rats reversed substantially within 1 h. However, the nasal
      absorption had not yet completely returned to the level without enhancer. 4. S.c.
      administered Org2766 accelerated the functional recovery from peripheral nerve
      damage in rats. However, the peptide did not facilitate nerve repair following
      i.n. administration with DM beta CD, in spite of the fact that Org2766 was well
      absorbed. I.v. injection of Org2766 was also ineffective.

PMID- 8306073
TI  - 5-HT3 antagonists reduce morphine self-administration in rats.
AB  - 1. The effects of the 5-HT3 receptor antagonists, ondansetron and tropisetron, on
      morphine consumption were studied in naive and morphine-dependent rats. 2. The
      administration of ondansetron (1 microgram kg-1, i.p. twice daily) 7 days prior
      to, and during a 21-day period of, morphine availability (increasing
      concentration from 0.1 to 0.4 mg ml-1) in 5% sucrose solution reduced opiate
      intake from the 9th day of morphine treatment. 3. The administration of
      ondansetron (0.1 microgram kg-1, i.p. twice daily) or tropisetron (0.1 microgram
      kg-1, i.p. twice daily) on the 14th day of the 21-day period of morphine
      treatment failed to reduce opiate consumption. Administration of the larger doses
      of tropisetron (1 microgram kg-1) or ondansetron (1 microgram kg-1) reduced
      morphine consumption. 4. After receiving 21 days of treatment with morphine alone
      or with the ondansetron or tropisetron regimens identified above, the sucrose
      solutions were substituted with tap water for 7 days. These detoxified rats were
      then allowed a free choice of sucrose or morphine for 10 days. Animals that had
      received concomitant treatment with ondansetron or tropisetron showed reduced
      morphine intake when compared with the controls treated with morphine only or
      with vehicle-treated controls. 5. The administration of cyproheptadine (100 or
      250 micrograms kg-1, i.p. twice daily) on the 14th day of 21-day morphine
      treatment failed to modify morphine intake and also failed to influence the
      subsequent intake of the opiate in the free choice situation. 6. It is concluded
      that ondasetron and tropisetron can reduce morphine intake in both naive and
      morphine-dependent rats.

PMID- 8306074
TI  - Modulation by nitric oxide of platelet-activating factor-induced albumin
      extravasation in the conscious rat.
AB  - 1. The objective of this study was to assess whether or not endogenous nitric
      oxide (NO) could mediate the hypotensive response to platelet-activating factor
      (PAF) and modulate PAF-induced microvascular albumin leakage in the conscious
      rat. 2. PAF (0.19 and 1.9 nmol kg-1, i.v.) evoked dose-dependent hypotension and
      significantly enhanced albumin extravasation in the large airways, pancreas,
      stomach and duodenum 15 min after its administration. Inhibition of NO synthesis
      by NG-nitro-L-arginine methyl ester (L-NAME, 0.125-2 mg kg-1, i.v.) produced
      marked dose-dependent increases in albumin accumulation (up to 290%) in large
      airways, liver, spleen, pancreas, kidney, stomach and duodenum as measured by the
      extravasation of Evans blue dye. L-NAME (2 mg kg-1) treatment markedly
      potentiated PAF (1.9 nmol kg-1)-induced albumin extravasation in these tissues,
      whereas it did not modify the hypotensive response to PAF. 3. Maintenance of mean
      arterial blood pressure at the level observed following 2 mg kg-1 L-NAME by
      infusion of noradrenaline (620-790 ng kg-1 min-1) neither affected significantly
      albumin extravasation nor potentiated the permeability effect of PAF in the
      vascular beds studied with the exception of large airways, where noradrenaline
      mimicked the effects of L-NAME. 4. These results indicate that inhibition of
      endogenous NO formation leads to an increase in albumin extravasation and to
      potentiation of the vascular permeability effect of PAF, whereas the hypotensive
      action of PAF seems to be independent of NO formation in the conscious rat. These
      data suggest an important role for NO in the regulation of albumin extravasation.

PMID- 8306075
TI  - [Ca2+]i-sensitive, IP3-independent Ca2+ influx in smooth muscle of rat vas
      deferens revealed by procaine.
AB  - 1. The actions of procaine (10 mM) on noradrenaline-induced effects on 45Ca
      influx, 45Ca-efflux, 45Ca-content, total inositol phosphates, inositol-1,4,5
      trisphosphate, and contractile status of the rat was deferens were examined. 2.
      Noradrenaline alone had no effect on 45Ca-influx or 45Ca-content, but released
      Ca2+ from intracellular stores as indicated by an increased 45Ca-efflux and
      increased total inositol phosphates, specifically inositol-1,4,5-trisphosphate,
      leading to contraction of the rat vas deferens. 3. Noradrenaline, in the presence
      of 10 mM procaine, increased 45Ca-influx and 45Ca-content. Procaine blocked the
      noradrenaline-induced 45Ca-efflux, the increase in total inositol phosphates, the
      increase in inositol-1,4,5-trisphosphate, and contraction. 4. The noradrenaline
      induced increase in 45Ca influx which was observed in the presence of procaine
      was abolished by phentolamine and nifedipine but was not altered significantly by
      propranolol suggesting that, in the presence of procaine, noradrenaline activates
      dihydropyridine-sensitive calcium channels through alpha-adrenoceptors. 5. These
      findings indicate that, in the rat vas deferens, noradrenaline induces
      contraction by releasing intracellularly stored Ca2+. The effects of procaine
      appear to be due to its ability to block the release of Ca2+ from intracellular
      stores. Furthermore, the simultaneous increase in 45Ca influx and inhibition of
      inositol-1,4,5-trisphosphate formation in tissues treated with procaine plus
      noradrenaline indicates that Ca2+ influx is independent of inositol-1,4,5
      trisphosphate formation.

PMID- 8306076
TI  - Inhibition by hydrochlorothiazide of insulin release and calcium influx in mouse
      pancreatic beta-cells.
AB  - 1. The effect of hydrochlorothiazide on insulin release, 36Cl- fluxes and 45Ca2+
      uptake was tested in beta-cell-rich mouse pancreatic islets. 2. At high glucose
      concentrations (10 and 20 mmol l-1), low concentrations of hydrochlorothiazide
      (0.1-1.0 mumol l-1) reduced insulin release by 22-42%. At lower glucose
      concentrations (3-8.5 mmol l-1) insulin release was not affected by the drug. 3.
      Neither short-term influx (3 min) nor net accumulation (60 min) of 36Cl- in the
      islets was affected by hydrochlorothiazide (0.1-500 mumol l-1). 4. Glucose
      stimulated 45Ca2+ uptake was significantly reduced by hydrochlorothiazide (1-10
      mumol l-1). 5. The data suggest that the diabetogenic effect of
      hydrochlorothiazide, at least in part, can be mediated by direct inhibition of
      insulin release from the pancreatic beta-cells. The inhibition is not mediated by
      reduced chloride fluxes but may rather be caused by inhibition of calcium uptake.

PMID- 8306077
TI  - Effects of atrial natriuretic peptide and nitroprusside on isolated pulmonary
      resistance and conduit arteries from rats with pulmonary hypertension.
AB  - 1. The relaxant effects of atrial natriuretic peptide (ANP) and nitroprusside
      were studied on prostaglandin F2 alpha (PGF2 alpha)-contracted preparations of
      pulmonary resistance vessels (internal diameter 200-500 microns) and main
      pulmonary arteries taken from rats with pulmonary hypertension induced by
      monocrotaline (105 mg kg-1, s.c., 4 weeks previously). Control rats received
      saline. 2. In preparations from monocrotaline-treated rats, the potencies
      (negative log EC50) of ANP on resistance vessels (8.45) and main pulmonary
      arteries (8.25) were similar to those obtained in vessels from control rats (8.78
      and 8.53 respectively), whereas those of nitroprusside were significantly less
      than in controls in both resistance vessels (7.13 compared with 7.63 in controls;
      three fold decrease in potency) and main pulmonary arteries (6.92 compared with
      8.17 in controls; 18 fold decrease in potency). 3. On pulmonary resistance
      vessels from monocrotaline-treated rats, the maximum relaxant responses to ANP
      and nitroprusside, and also to pinacidil, were increased compared with controls,
      and reversal of the PGF2 alpha-induced contraction by these drugs was greater
      than 100%. In contrast, on main pulmonary arteries from monocrotaline-treated
      rats, the maximum relaxations to ANP and nitroprusside were not increased
      relative to controls, and reversal of PGF2 alpha was not greater than 100%. 4.
      Since the high potency of ANP on pulmonary resistance and conduit arteries is
      retained in vessels from rats with pulmonary hypertension, whether induced by
      monocrotaline (this study) or by chronic hypoxia (previous findings), it is
      postulated that elevation of plasma levels of ANP by use of drugs that inhibit
      the breakdown of this endogenous peptide, may be one approach to the
      pharmacological treatment of pulmonary hypertension.

PMID- 8306078
TI  - Cardiotonic actions of selective phosphodiesterase inhibitors in rat isolated
      ventricular cardiomyocytes.
AB  - 1. The contractile effects of the novel cardiotonic agent HN-10200 (2-[3-methoxy
      5-methylsulphinyl-2-thienyl]-1H-imidazo-[4,5-c]-p yri dine hydrochloride), were
      examined and comparisons made with the responses obtained to a structurally
      similar compound, sulmazole, and to a number of other compounds which are known
      to inhibit phosphodiesterase (PDE) isoenzymes with differing selectivities;
      namely, enoximone (PDE III inhibitor), Ro 20-1724 (PDE IV inhibitor) and 3
      isobutyl-1-methylxanthine (non-selective PDE inhibitor). 2. Contractile function,
      as measured by mechanical shortening, and biochemical systems involving cyclic
      AMP were investigated in ventricular cardiomyocytes isolated from adult Sprague
      Dawley rats (200-250 g). 3. HN-10200 exerted a concentration-dependent (10(-8) M
      10(-4) M) positive contractile effect, which was independent of alpha- or beta
      adrenoceptor, or histamine receptor stimulation. 4. The efficacies of the
      contractile responses to the PDE inhibitors were of the order: HN-10200 > IBMX >
      sulmazole > enoximone and maximum stimulations, which were obtained at
      concentrations of 10(-4) M, were 54 +/- 4%, 41 +/- 7%, 38 +/- 7% and 26 +/- 5%
      (mean +/- s.e.) greater than basal levels, respectively (n = 6); the basal value
      of contractile amplitude (dL), in the absence of PDE inhibitors was 7.39 +/-
      0.18% (mean +/- s.e.). Ro 20-1724 did not have any effect on contractile
      activity. 5. Due to low basal levels of cyclic nucleotides in isolated cells,
      accumulation of cyclic AMP due to the presence of the PDE inhibitors was detected
      only when the levels of cyclic nucleotide were enhanced with forskolin (10
      microM). 6. The PDE inhibitors increased levels of cyclic AMP only at
      concentrations> 10-4 M. HN-10200 and sulmazole had similar concentration
      dependent profiles for the accumulation of cyclic AMP; their potencies were lower
      than that of IBMX (concentrations of forskolin required to increase cyclic AMP by
      4 pmol mg-1 protein, in the presence of maximum concentrations of the PDE
      inhibitors, were 13 +/- 311M, 14 +/- 3 JAM and 3 +/- 0.6 JAM [mean +/- s.e.],
      respectively).7. These results indicate that a similar mechanism, probably
      through a weak inhibition of the cyclic AMP-specific PDE isoenzymes, is
      responsible for the increase in levels of cyclic AMP by HN-10200 and sulmazole.
      However, cyclic AMP is only partially responsible for the positive contractile
      effect of HN-10200 and, similarly, sulmazole and IBMX. The lack of apparent
      increase in levels of cyclic AMP by enoximone, highlights its degree of
      selectivity for the PDE III isoenzyme, such that the PDE IV isoform is still
      present in sufficient quantity to degrade cyclic AMP within the cell. On the
      other hand,the potent action of Ro 20-1724 on accumulation of cyclic AMP, in
      addition to the lack of effect on contractile function, is in agreement with the
      selectivity of this compound for the PDE IV isoenzyme and compartmentalization of
      cyclic AMP in rat isolated ventricular cardiomyocytes.

PMID- 8306079
TI  - Comparison of haemoconcentration induced by big endothelin-1 and endothelin-1 in
      mice.
AB  - 1. The profile of haemoconcentration induced by big endothelin-1(big ET-1), a
      precursor of endothelin-1 (ET-1), was compared with that induced by endothelin-1
      in mice. 2. ET-1(1.5 nmol kg-1, i.v.) increased haematocrit in mice, which
      reached a maximum at 5 min and then returned to the control value within 30 min
      after the administration, this occurred at the same time as changes in the plasma
      immunoreactive endothelin-1 and rat atrial natriuretic peptide (rANP)-like
      activities (IR-ET-1 and IR-rANP, respectively). 3. Big ET-1(2.5-15 nmol kg-1,
      i.v.) also caused a significant and dose-dependent increase in haematocrit, that
      lasted over 3 h although elevated plasma IR-ET-1 and IR-rANP had almost been
      restored to the initial levels within 10 min after big ET-1 injection. 4. A
      metalloproteinase inhibitor, phosphoramidon (10 mg kg-1, i.v.), which inhibits
      the activity of endothelin converting enzyme (ECE), delayed the onset of big ET-1
      induced haemoconcentration, but failed to alter the maximal value and the
      duration of the haemoconcentration. 5. Pretreatment with phosphoramidon (10 mg kg
      1, i.v.) did not affect the big ET-1-induced change in plasma IR-ET-1, while
      significant delay of the disappearance of plasma IR-rANP and significant
      suppression of a sustained increase in tissue IR-ET-1 were observed. 6. These
      results suggest that ET-1, not in plasma but in tissue, plays an important role
      in the pathogenesis of big ET-1-induced long-lasting haemoconcentration, in which
      unknown factors besides rANP are involved.

PMID- 8306080
TI  - Pharmacological characterization of the metabotropic glutamate receptor
      inhibiting D-[3H]-aspartate output in rat striatum.
AB  - 1. The effects of several agonists of the metabotropic glutamate receptor (mGluR)
      were studied in adult rat striatal slices by measuring (i) KCl (30 mM)-induced
      output of previously taken up D-[3H]-aspartate (Asp), (ii) forskolin (30 microM)
      induced adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation and (iii)
      phophoinositide (PI) hydrolysis. 2. K(+)-induced efflux of D-[3H]-Asp was
      inhibited by the following mGluR agonists: (1S,3S,4S)-(carboxycyclopropyl)glycine
      (L-CCG-I), (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and
      quisqualic acid (Quis). 2-Amino-4-phosphonobutyrate (L-AP4) was inactive up to
      300 microM. The maximal inhibition of D-[3H]-Asp output was 60 +/- 8%. The EC50s
      of mGluR agonists were: 0.5 microM for L-CCG-I, 100 microM for 1S,3R-ACPD and 100
      microM for Quis. 3. Forskolin-induced cyclic AMP accumulation was also inhibited
      by mGluR agonists. The maximal inhibition was 50 +/- 4% and was obtained at a
      concentration of 10 microM for L-CCG-I and 100 microM for 1S,3R-ACPD. The EC50s
      for this inhibition were: 0.9 microM for L-CCG-I and 20 microM for 1S,3R-ACPD.
      Quis (300 microM) inhibited cyclic AMP accumulation by approximately 20%. L-AP4
      slightly potentiated cyclic AMP accumulation. 4. PI hydrolysis was stimulated by
      mGluR agonists. The most potent compound was Quis (100 microM), which increased
      inositol phosphate formation up to 2.2 fold over control values. Its EC50 was 15
      microM. L-CCG-I and 1S,3R-ACPD increased inositol phosphate formation by
      approximately 1.8 fold and their EC50 values were 30 and 25 microM, respectively.
      L-AP4 did not affect PI hydrolysis. 5. In conclusion, mGluR agonists that reduce
      D-[3H]-Asp output have a pharmacological profile similar to that of mGluR
      agonists inhibiting cyclic AMP accumulation. L-CCG-I appears to be a relatively
      selective agonist for the mGluR receptor which inhibits D-[3H]-Asp efflux and
      cyclic AMP accumulation,while Quis appears to act preferentially on the mGluR
      receptor linked to the metabolism of PIs.

PMID- 8306081
TI  - Dual contractile effects of ATP released by field stimulation revealed by effects
      of alpha,beta-methylene ATP and suramin in rat tail artery.
AB  - 1. The field stimulation-induced release of endogenous ATP and noradrenaline (NA)
      and contractile response in rat isolated tail artery were examined. The release
      of ATP was studied by extracellular electrophysiological recording and that of NA
      by a novel voltammetrical technique. The effects of the P2-purinceptor
      antagonist, suramin, on these parameters were compared with those of alpha,beta
      methylene ATP, a P2X-purinoceptor desensitizing agent. 2. Neither alpha,beta
      methylene ATP (10 microM) nor suramin (100-500 microM) had significant effects on
      the extracellularly recorded nerve terminal action potential but both abolished
      the ATP-induced excitatory junction current caused by stimulation at 0.1 Hz.
      Neither agent affected significantly the voltammetrically measured release of NA
      induced by 10 or 100 pulses at 20 Hz. 3. Combined blockade of both postjunctional
      alpha 1- and alpha 2-adrenoceptors by prazosin and yohimbine (both 0.1 microM)
      profoundly depressed the contractile response to 10 pulses at 20 Hz. The small
      and fast residual contraction in the presence of these agents was abolished by
      alpha,beta-methylene ATP (10 microM) and inhibited by suramin in a concentration
      dependent manner (10-500 microM; IC50 75 microM) and was hence probably caused by
      ATP or a related nucleotide. 4. When added first, alpha,beta-methylene ATP (10
      microM) or suramin (100-500 microM) delayed the onset and enhanced the amplitude
      of the neurogenic contraction. This enhanced response was abolished by further
      addition of prazosin and yohimbine (both 0.1 microM). 5. The K+ channel blocker,
      tetraethylammonium (10 mM), dramatically enhanced the contractile response to 100
      pulses at 1 Hz and caused it to become diphasic. Addition of alpha,beta-methylene
      ATP (10 microM)or suramin (100-500 microM) abolished the large initial twitch
      component of this contraction and depressed the tonic phase.6. Like alpha,beta
      methylene ATP, suramin (500 microM) had no effect on the contraction caused by
      exogenous NA (1O nM-l10 microM) or KCI (60 mM); both agents almost abolished the
      contraction caused by ATP(100 microM).7. In conclusion, (i) the contractile
      response of rat tail artery to electrical field stimulation is mediated by both
      ATP and NA, and is thus an expression of ATP-NA co-transmission, (ii) the
      released ATP exerts two opposite effects via 'P2x-like' purinoceptors, triggering
      the initial rapid phase of the neurogenic contraction and restricting the NA
      mediated component of the contraction; and (iii) the source and possible
      physiological role of the ATP which causes the inhibitory effect are unknown at
      present.

PMID- 8306082
TI  - Binding and structure-activity-relation of benzo[f]isoquinoline- and norcodeinone
      derivatives at mu-opioid receptors in the rat cerebral cortex.
AB  - 1. We have probed the ligand binding site of the mu-opioid receptor using a
      series of isoquinoline- and norcodeinone-derivatives; in these morphine- and
      codeine-analogues, the position of the piperidine-nitrogen as well as its
      mobility is altered relative to that found in morphine. 2. The mu-receptor in rat
      cortical membranes was labelled with [3H]-naloxone and competition experiments
      were carried out in the absence and presence of Gpp(NH)p and NaCl: conditions,
      which are associated with affinity shifts for agonists whilst antagonist affinity
      remains unaffected. Moving the piperidine-nitrogen closer to the phenolic ring or
      reducing its mobility by incorporation into an additional ring drastically
      decreases the affinity. 3. In contrast, we find that the piperidine-nitrogen in a
      distal position is well tolerated provided that additional structural criteria,
      in particular a phenolic hydroxyl-group and a 6 carbon ring corresponding to ring
      C in morphine, are met. This assumption was verified by the synthesis of WB4/PH
      (4aR, 10bS, 11R)-10, 11-epoxy-1, 2, 3, 4, 5, 6-hexahydro-9-hydroxy-3-methyl
      4a,10b-butano- benzo[f]isochinolin-12-on(10). This compound is an agonist with an
      affinity comparable to that of morphine. 4. We therefore conclude that both the
      mobility of the piperidine nitrogen of the ligand and of its counterpart anionic
      site in the ligand binding pocket of the mu-opioid receptor (presumably aspartic
      acid) are important determinants for fruitful interaction. The mobility of the
      anionic site is restricted in one direction but is sufficient to bridge the 2A
      distance that exists between the position of the nitrogen in morphine and WB4/PH.

PMID- 8306083
TI  - Mechanism of rat uterine smooth muscle contraction induced by endothelin-1.
AB  - 1. Endothelin (ET)-1 has been demonstrated to cause contraction of uterine smooth
      muscle. We investigated the role of ET receptor subtypes (ETA and ETB receptors)
      in ET-1-induced contraction of rat uterine smooth muscle by using the ETA
      receptor antagonist BQ-123 and the ETB receptor agonist BQ-3020. 2. ET-1 caused a
      contraction with superimposed oscillations of the rat isolated uterus suspended
      in Krebs-Ringer solution; both the amplitude of contraction as well as the
      oscillation frequency increased in a dose-dependent manner (10(-11)-10(-7)M). 3.
      BQ-123 (10(-6)M) markedly shifted the dose-response curve of ET-1 for both
      contractile effects and oscillation frequency to the right. 4. BQ-3020 (10(-11)-3
      x 10(-7) M) did not cause uterine contraction; neither did it affect the dose
      response curve of ET-1 for either the contractile effect or the increase in
      oscillation frequency. Thus, stimulation of ETB receptors is not involved in
      these responses. 5. The present findings suggest that ET-1-induced contractile
      responses and the increase in oscillation frequency in rat uterine smooth muscle
      is mediated through ETA receptors, and that ETB receptors play no role in these
      responses.

PMID- 8306084
TI  - Induction of bradykinin B1 receptors in vivo in a model of ultra-violet
      irradiation-induced thermal hyperalgesia in the rat.
AB  - 1. The role of bradykinin B1 receptors in the thermal hyperalgesia following
      unilateral ultra-violet (u.v.) irradiation of the hindpaw of rats has been
      investigated. 2. In non-irradiated (naive) animals the B1 receptor agonist des
      Arg9-bradykinin and bradykinin (BK) (up to 1 mumol kg-1 i.v.) had no effect on
      withdrawal latency to a noxious heat stimulus when administered 60 min before
      testing. 3. Following exposure of one hindpaw to strong u.v. irradiation the
      withdrawal latency of the u.v.-treated paw to radiant noxious heat fell by a
      maximum of 50% after 48 h. There was no reduction in latency in the contralateral
      paw. 4. des-Arg9-BK (1-100 nmol kg-1 i.v.) administered 24 h after u.v. exposure
      caused a further dose-dependent fall (50 +/- 4% reduction from saline injected
      animals at 100 nmol kg-1 i.v.) in withdrawal latency in the u.v.-treated paw when
      measured 60 min after injection. The withdrawal latency of the contralateral paw
      was also reduced but to a lesser extent following des-Arg9-BK (100 nmol kg-1
      i.v.) with a maximum reduction of 19 +/- 3%. 5. Bradykinin also induced a further
      reduction in withdrawal latency (33 +/- 5% reduction at 1 mumol kg-1) although it
      was not as effective as des-Arg9-BK. Bradykinin did not reduce the withdrawal
      latency in the contralateral paw. 6. The hyperalgesic action of both des-Arg9-BK
      (10 nmol kg-1 i.v.) and bradykinin (100 nmol kg-1 i.v.)were antagonized by the B,
      receptor antagonist, des-Arg9,Leu8-BK (200 nmol kg-1 i.v.) but not by the B2
      receptor antagonist, HOE 140 (0.5 .micromol kg-1 i.v.).7. The results suggest
      that in conditions of inflammatory hyperalgesia bradykinin B1 receptors are
      induced both locally and distant to the inflamed area, activation of which leads
      to further thermal hyperalgesia. In addition, in these conditions bradykinin
      appears to act predominantly via B1 receptors,presumably after degradation to des
      Arg9-BK.

PMID- 8306085
TI  - Effects of sumatriptan on the cerebral intraparenchymal microcirculation in the
      cat.
AB  - 1. Sumatriptan, a 5-hydroxytryptamine (5-HT)1-like receptor agonist, is effective
      against the headache of migraine. The effects of sumatriptan injected via the
      carotid artery on the cerebral microcirculation were studied in 10 anaesthetized
      cats. 2. The local cerebral blood volume (CBV), mean transit time of blood (MTT)
      and cerebral blood flow (CBF) in the parieto-temporal cortex were measured by a
      photoelectric method. CBV represents the cumulative dimensions of the cerebral
      microvessels. 3. Sumatriptan at 5 and 50 micrograms kg-1 had no significant
      effects on the CBV, MTT, CBF, and mean arterial blood pressure (MABP); 500
      micrograms kg-1 of sumatriptan reduced the CBV, prolonged the MTT, and decreased
      the CBF (approximately -20%) without affecting the MABP. Sumatriptan, 5 mg kg-1,
      elicited transient reductions in CBV and CBF, which were attributable to the
      rapid and marked falls of MABP seen with this dose. 4. Thus, while a high dose of
      sumatriptan (500 micrograms kg-1) exhibits direct vasoconstrictor actions on the
      cerebral vessels, low doses of sumatriptan, within the therapeutic range, elicit
      no vasoconstriction. The data do not support a vasoconstrictor action of
      sumatriptan playing a primary role in reversing the headache of migraine.

PMID- 8306086
TI  - Homologous and heterologous desensitization of histamine H1- and ATP-receptors in
      the smooth muscle cell line, DDT1MF-2: the role of protein kinase C.
AB  - 1. The possible role of protein kinase C (PKC) in homologous and heterologous
      desensitization of histamine H1- and ATP-receptors has been studied in monolayers
      of cultured vas deferens smooth muscle cells (DDT1MF-2). Cells were loaded with
      the calcium-sensitive fluorescent dye fura-2 and increases in intracellular free
      Ca2+ concentration ([Ca2+]i) monitored in response to histamine H1- or ATP
      receptor activation. 2. Histamine and ATP stimulated the release of Ca2+ from
      intracellular Ca2+ stores and Ca2+ influx across the plasma membrane. Activation
      of PKC with the phorbol ester beta-phorbol-12,13 dibutyrate (PDBu; 1 microM)
      attenuated histamine (100 microM) and ATP (10 microM)-induced release of
      intracellular Ca2+ and Ca2+ influx. 3. The selective PKC inhibitor, Ro 31-8220
      (10 microM), reversed the PDBu-induced attenuation of histamine (100 microM)
      stimulated Ca2+ responses. 4. Histamine H1- and ATP-receptors are readily
      susceptible to homologous desensitization since short-term exposure to histamine
      or ATP (450 s) attenuated the Ca2+ responses elicited by a second application of
      the same agonist. Furthermore, H1-receptor activation-induced heterologous
      desensitization of ATP stimulated Ca2+ responses and vice versa. 5. Homologous
      and heterologous desensitization of histamine and ATP Ca2+ responses still
      occurred in the presence of the PKC inhibitor, Ro 31-8220 (10 microM). 6. These
      data suggest that PKC activation can attenuate histamine H1- and ATP-receptor
      mediated Ca2+ responses. However, based on our experimental data, PKC-independent
      mechanisms appear to be involved in the homologous and heterologous
      desensitization of histamine H1- and ATP-receptor mediated Ca2+ responses in
      DDT1MF-2 cells.

PMID- 8306087
TI  - Regional and cardiac haemodynamic effects of NG, NG,dimethyl-L-arginine and their
      reversibility by vasodilators in conscious rats.
AB  - 1. A series of experiments was carried out on 3 separate groups of male Long
      Evans rats, chronically instrumented for the measurement of regional
      haemodynamics, to compare the effects of NG,NG, dimethyl-L-arginine (ADMA) and NG
      monomethyl-L-arginine (L-NMMA), and their reversibility by the nitric oxide
      donors, S-nitroso-N-acetyl-penicillamine (SNAP), S-nitroso-glutathione (SNOG),
      sodium nitroprusside (SNP), and the vasodilator, hydralazine. 2. As previously
      reported for L-NMMA, ADMA (1-100 mg kg-1) caused dose-dependent pressor and
      bradycardic effects, accompanied by renal, mesenteric and hindquarters
      vasoconstrictions. The magnitude and duration of these effects were similar for
      ADMA and L-NMMA, consistent with their being equipotent inhibitors of nitric
      oxide synthase. 3. Infusion of SNAP or SNOG (300 micrograms kg-1 h-1) after
      injection of ADMA or L-NMMA (100 mg kg-1) reversed the pressor but did not
      abolish the vasoconstrictor, effects of ADMA or L-NMMA. However, a higher dose of
      SNAP (3 mg kg-1 h-1) caused complete reversal of the pressor and mesenteric
      haemodynamic effects of ADMA (100 mg kg-1), although its renal and hindquarters
      vasoconstrictor effects were not abolished. 4. Infusion of SNP (300 micrograms kg
      1 h-1) after administration of L-NMMA (100 mg kg-1), caused complete reversal of
      its pressor and mesenteric and hindquarters haemodynamic effects, and reduced
      substantially its renal vasoconstrictor action; hydralazine (7.5 mg kg-1 h-1) was
      almost as effective as SNP in reversing all these variables. 5. In animals
      chronically instrumented for the measurement of cardiac haemodynamics, ADMA(100
      mg kg-1) caused a pressor effect accompanied by a rise in central venous
      pressure, and reductions in heart rate, cardiac index, stroke index, peak aortic
      flow, maximum rate of rise of aortic flow and total peripheral conductance. The
      reversal of the pressor effect of ADMA by SNAP (300 microg kg-1 h-1) was
      accompanied by a reduction of central venous pressure below resting levels and a
      further diminution of stroke index; all other variables showed an increase, but
      they still remained below resting levels (with the exception of heart rate).6.
      Thus, following inhibition of NO synthesis, pharmacological intervention with NO
      donors, or other vasodilators, may cause normalisation of the mean arterial
      pressure without necessarily returning all associated cardiovascular variables to
      normal.

PMID- 8306088
TI  - Prejunctional modulation of noradrenaline release in mouse and rat vas deferens:
      contribution of P1- and P2-purinoceptors.
AB  - 1. Prejunctional purinoceptors modulating the release of noradrenaline were
      compared in mouse and rat vas deferens. Tissue slices were preincubated with [3H]
      noradrenaline and then superfused and stimulated electrically, in most
      experiments by trains of 60 pulses, 1 Hz. 2. In mouse vas deferens, 2
      chloroadenosine (IC50 0.24 microM), beta,gamma-methylene-ATP (IC50 3.8 microM),
      alpha,beta-methylene-ATP (IC50 2.9 microM) and 2-methylthio-ATP (only 30 microM
      tested) reduced the evoked overflow of tritium. 8-Cyclopentyl-1,3
      dipropylxanthine (DPCPX), 10 nM, antagonized the effect of 2-chloro-adenosine
      (apparent pKB 10.2) as well as of beta,gamma-methylene-ATP (apparent pKB 9.6) and
      alpha,beta-methylene-ATP. Suramin, 300 microM, attenuated the effect of 2
      chloroadenosine at best very slightly, antagonized the effect of beta,gamma
      methylene-ATP (apparent pKB 4.5) and, when combined with DPCPX 10 nM, caused a
      further marked shift to the right of the concentration-response curve of
      beta,gamma-methylene-ATP beyond the shift produced by DPCPX alone. 3. In rat vas
      deferens, 2-chloroadenosine (IC50 0.20 microM), beta,gamma-methylene-ATP (IC50
      4.8 microM), alpha,beta-methylene-ATP (IC50 3.0 microM) and 2-methylthio-ATP
      (only 30 microM tested) also reduced the evoked overflow of tritium. DPCPX, 10
      nM, antagonized the effect of 2-chloroadenosine (apparent pKB 9.7) as well as of
      beta,gamma-methylene-ATP (apparent pKB 9.6) and alpha,beta-methylene-ATP.
      Suramin, 300 microM, did not change the effect of 2-chloroadenosine, attenuated
      the effect of beta,gamma-methylene-ATP at best very slightly and, when combined
      with DPCPX, caused at best a very small shift to the right of the concentration
      response curve of beta,gamma-methylene-ATP beyond the shift produced by DPCPX
      alone.4. It is concluded that prejunctional purinoceptor mechanisms in mouse and
      rat vas deferens are similar. In either species, both nucleosides such as
      adenosine and nucleotides such as beta,gamma-methylene-ATP activate a common
      release-inhibiting receptor which is a Pl- or, more specifically, A1
      purinoceptor.There seems to be no need to postulate the existence of a novel
      prejunctional P3-purinoceptor.Moreover, the sympathetic terminal axons possess an
      additional P2-purinoceptor in both species which is activated by some nucleotides
      such as beta,gamma-methylene-ATP and 2-methylthio-ATP, although the activation of
      the P2-purinoceptor by beta,gamma-methylene-ATP is difficult to demonstrate in
      the rat.

PMID- 8306089
TI  - EDRF release from canine coronary artery by lectins.
AB  - 1. The effect of wheat germ agglutinin (WGA), concanavalin A (Con A) and lentil
      lectin agglutinin (LCA) were investigated on pre-contracted canine coronary
      artery rings in vitro. 2. In endothelium-intact canine coronary artery,
      contracted with the thromboxane A2-analogue, U46619, WGA relaxed the tissue in a
      concentration-dependent manner, with an inhibitory concentration (IC50) of 112 +/
      17 nM (n = 6). In the absence of an endothelium, WGA did not cause any
      relaxation of the tissue. 3. In endothelium-intact canine coronary artery,
      contracted with the thromboxane A2-analogue, U46619. LCA relaxed the tissue in a
      concentration-dependent manner, with an inhibitory concentration (IC50) of 423.1
      +/- 41 nM (n = 6). In the absence of an endothelium, LCA produced a 20.1 +/- 1.1%
      (n = 6) relaxation at the highest concentration tested (3 microM). 4.
      Concanavalin A (Con A) relaxed canine coronary artery in a partial endothelium
      dependent manner with an IC50 of 104 +/- 19 nM on endothelium-intact coronary
      artery and an IC50 of 1.3 +/- 0.3 microM (n = 6) on endothelium-denuded tissues.
      5. The relaxation effects of WGA were attenuated by 1 mM NG-monomethyl L-arginine
      (L-NMMA) and completely inhibited by haemoglobin (3 microM), methylene blue (10
      microM) and LY 83583 (30 microM). Ibuprofen had no effect on WGA-induced
      relaxation. 6. The relaxant effects of WGA were reversed by addition of 20 mM N
      acetyl-D-glucosamine (GlcNAc) and N-acetyl-D-galactosamine (Ga1NAc) but not by
      alpha-mannose, D-(+)-galactose, and beta-lactose, whereas the endothelin
      dependent relaxations to LCA and Con A were unaffected. 7.The endothelium
      dependent relaxation induced by the lectins was unaffected by pretreatment of the
      tissue with 1 microM atropine.8. In the absence of extracellular calcium, WGA was
      also able to release EDRF suggesting that WGA acts through a second messenger
      system to release intracellular calcium.9. We suggest that WGA acts as an agonist
      to release EDRF from endothelial cells possibly by binding to a sugar moiety,
      specific receptor or adhesion molecules on the endothelial cell surface.

PMID- 8306090
TI  - Cross-tolerance between delta-9-tetrahydrocannabinol and the cannabimimetic
      agents, CP 55,940, WIN 55,212-2 and anandamide.
AB  - 1. Mice pretreated intraperitoneally for 2 days with delta-9-tetrahydrocannabinol
      (delta-9-THC) at a dose of 20 mg kg-1 day-1 and then challenged intravenously
      with this drug, 24 h after the second pretreatment, showed a 6 fold tolerance to
      the hypothermic effect of delta-9-THC. This pretreatment also induced tolerance
      to the hypothermic effects of the cannabimimetic agents, CP 55,940 (4.6 fold) and
      WIN 55,212-2 (4.9 fold), but not to the hypothermic effect of the putative
      endogenous cannabinoid, anandamide. 2. Vasa deferentia removed from mice
      pretreated intraperitoneally with delta-9-THC twice at a dose of 20 mg kg-1 day-1
      were less sensitive to its inhibitory effect on electrically-evoked contractions
      than vasa deferentia obtained from control animals. The cannabinoid pretreatment
      induced a 30 fold parallel rightward shift in the lower part of the concentration
      response curve of delta-9-THC and a marked reduction in the maximal inhibitory
      effect of the drug. It also induced tolerance to the inhibitory effects on the
      twitch response of CP 55,940 (8.7 fold), WIN 55,212-2 (9.6 fold) and anandamide
      (12.3 fold). 3. The results confirm that cannabinoid tolerance can be rapid in
      onset and support the hypothesis that it is mainly pharmacodynamic in nature. The
      finding that in vivo pretreatment with delta-9-THC can produce tolerance not only
      to its own inhibitory effect on the vas deferens but also to that of three other
      cannabimimetic agents, suggests that this tissue would be suitable as an
      experimental model for investigating the mechanisms responsible for cannabinoid
      tolerance. 4. Further experiments are required to establish why tolerance to
      anandamide-induced hypothermia was not produced by a pretreatment with delta-9
      THC that did induce tolerance to the hypothermic effects of delta-9-THC, CP
      55,940 and WIN 55,212-2 and to the inhibitory effects of delta-9-THC,CP 55,940,
      WIN 55,212-2 and anandamide on the twitch response of the vas deferens.

PMID- 8306091
TI  - PPADS selectively antagonizes P2X-purinoceptor-mediated responses in the rabbit
      urinary bladder.
AB  - 1. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), an inhibitor of
      P2X-purinoceptor-mediated responses in rabbit vas deferens, was investigated for
      its ability to antagonize contractions evoked by alpha,beta-methylene ATP
      (alpha,beta-MeATP), carbachol and electrical field stimulation in the rabbit
      urinary bladder detrusor muscle. 2. PPADS. (1-30 microM) caused concentration
      dependent inhibition of contractions to the stable P2X-purinoceptor agonist,
      alpha,beta-MeATP, decreasing the maximum response to alpha,beta-MeATP (30 microM)
      at concentrations of 3-30 microM. The pD2 value for alpha,beta-MeATP in the
      absence of PPADS was 6.52 +/- 0.10 (8). In the presence of PPADS at
      concentrations of 1, 3, 10 and 30 microM the negative log concentrations of
      alpha,beta-MeATP that cause the same contractile response as the pD2 value were
      significantly different from control, being respectively 6.17 +/- 0.09 (8), 5.64
      +/- 0.12 (7), 5.15 +/- 0.23 (7) and 4.78 +/- 0.22 (5). 3. PPADS (1-30 microM)
      caused concentration-dependent inhibition of contractions to stimulation of
      intramural purinergic nerves (1-32 Hz). There was a greater inhibition at lower
      frequencies (1-8 Hz) than at higher frequencies (16-32 Hz). PPADS, 30 microM, did
      not produce significantly greater antagonism than 10 microM. 4. PPADS (30 microM)
      had no significant influence on the contractile potency of carbachol: the pD2
      values of carbachol in the absence and presence of PPADS were not significantly
      different being 6.42 +/- 0.16 (5) and 6.33 +/- 0.18 (5), respectively. However,
      PPADS caused a small, but significant, suppression of the maximal response of
      carbachol, reducing it by approximately 9%. 5. Radioligand binding studies
      carried out on rabbit bladder membranes with [3H]-alpha,beta-methylene ATP([3H]
      alpha,beta-MeATP) showed that PPADS concentration-dependently inhibited the
      binding of [3H]-alpha,beta-MeATP to P2X-purinoceptors, while the binding of [3H]
      quinuclidinyl benzilate to muscarinic cholinoceptors was not affected.6. Thus,
      PPADS (1-30 microM) antagonized responses mediated via P2X-purinoceptors in the
      rabbit urinary bladder. It was selective for P2-purinoceptor-mediated
      contractions rather than those mediated via muscarinic receptors. Binding studies
      demonstrated that the antagonistic effect of PPADS is via a direct interaction
      with P2x-purinoceptors.

PMID- 8306092
TI  - Suppression by intradermal administration of heparin of eosinophil accumulation
      but not oedema formation in inflammatory reactions in guinea-pig skin.
AB  - 1. Heparin is widely used in the treatment of thrombotic disorders and as an aid
      in surgery. Anti-inflammatory effects of heparin have also been described. In
      this study, we have investigated the effects of locally-injected heparin on the
      oedema formation and eosinophil accumulation induced by various inflammatory
      stimuli in guinea-pig skin. 2. Heparin dose-dependently suppressed the
      accumulation of 111In-labelled eosinophils induced by i.d. injection of zymosan
      activated plasma (ZAP). The 111In-eosinophil accumulation induced by other
      inflammatory stimuli (compound 48/80, platelet activating factor, interleukin-8
      and in a passive cutaneous anaphylaxis reaction) was also suppressed by locally
      injected heparin. 3. Oedema formation in response to these same stimuli was not
      altered by the local injection of heparin. 4. Fucoidin, a negatively-charged
      sulphated algal polymer, had no effect on the 111In-eosinophil accumulation or
      oedema formation induced by ZAP. Nevertheless, fucoidin significantly suppressed
      the oedema formation induced by i.d. injection of cationic protein-containing
      extracts of Schistosoma mansoni larvae. Heparin also inhibited oedema induced by
      the extracts, suggesting that both fucoidin and heparin were effectively
      neutralizing the cationic protein of the extracts to inhibit their oedema
      inducing activity. 5. Thus, heparin significantly inhibited the accumulation of
      111In-eosinophils, but not oedema formation, induced by various inflammatory
      stimuli. This, taken together with the lack of effect of fucoidin, suggests that
      heparin interferes with the process of eosinophil trafficking by a mechanism that
      does not depend on neutralisation of the charge of the stimulatory molecules.

PMID- 8306093
TI  - Effect of the platelet-activating factor antagonist, TCV-309, and the cyclo
      oxygenase inhibitor, ibuprofen, on the haemodynamic changes in canine
      experimental endotoxic shock.
AB  - 1. The present study was conducted in order to examine the effects of the
      platelet-activating factor (PAF) antagonist, TCV-309, and the cyclo-oxygenase
      inhibitor, ibuprofen, on the acute haemodynamic responses to endotoxin in
      anaesthetized dogs. 2. Endotoxin (2 mg kg-1, i.v.) induced a severe hypotension
      by decreasing both total peripheral resistance (TPR) and cardiac output.
      Endotoxin also decreased central venous pressure and increased effective vascular
      compliance (EVC), indicating a blood pooling in the capacitance vessels. 3. The
      endotoxin-induced hypotension but not the fall in cardiac output, was markedly
      attenuated by ibuprofen. Ibuprofen abolished the decrease in TPR and even caused
      a systemic vasoconstriction. Ibuprofen abolished the increase in EVC. 4. The
      hypotension caused by endotoxin was attenuated by TCV-309 to a lesser extent than
      ibuprofen. However, the reduction in cardiac output produced by endotoxin was
      markedly attenuated by the PAF antagonist. TCV-309 also abolished the increase in
      EVC. In contrast to ibuprofen, TCV-309 did not affect the decrease in TPR caused
      by endotoxin. 5. Combined treatment with ibuprofen and TCV-309 markedly
      attenuated the endotoxin-induced hypotension, but not the fall in cardiac output.
      Nevertheless, when compared with animals treated with ibuprofen alone, treatment
      with ibuprofen and TCV-309 partly attenuated the endotoxin-induced reduction in
      cardiac output and systemic vasoconstriction. 6. These data indicate that
      dilatation of both resistance vessels and capacitance vessels contributes to the
      endotoxin-induced hypotension. It is suggested that (i) both prostanoids and PAF
      are involved in dilatation of capacitance vessels, (ii) prostanoids, but not PAF
      cause dilatation of resistance vessels and(iii) PAF may partly contribute to
      prostanoid-independent reduction in cardiac output in acute canine experimental
      endotoxin shock.

PMID- 8306094
TI  - Protection by scoparone against the alterations of plasma lipoproteins, vascular
      morphology and vascular reactivity in hyperlipidaemic diabetic rabbit.
AB  - 1. The in vivo pharmacological effects of scoparone (6,7-dimethoxycoumarin) in a
      hyperlipidaemic diabetic rabbit model were investigated. 2. Three groups of
      rabbits were studied: (1) normal, (2) hyperlipidaemic and diabetic-untreated and
      (3) hyperlipidaemic and diabetic-scoparone treated. The hyperlipidaemic diabetic
      rabbits were fed with 1% cholesterol and treated with alloxan, a diabetogenic
      agent. The plasma levels of total cholesterol, total triglyceride, very low
      density lipoprotein (VLDL) cholesterol, low density lipoprotein (LDL) cholesterol
      and high-density lipoprotein (HDL) cholesterol were markedly increased as soon as
      the rabbit became diabetic at the second week. Scoparone-treatment (5 mg kg-1 day
      1, s.c.) significantly reduced the plasma lipid and lipoprotein cholesterol
      levels of the hyperlipidaemic diabetic rabbit to 73.3% of total cholesterol,
      48.3% of total triglyceride, 66.0% of VLDL cholesterol, 55.7% of LDL cholesterol
      and 79.5% of HDL cholesterol. 3. Six weeks after cholesterol-feeding, the aortic
      arch and thoracic aorta were dissected for morphological and functional studies.
      In vascular rings from the untreated hyperlipidaemic diabetic rabbit, there was
      intimal thickening with accumulation of fatty streaks, foam cells and migration
      of smooth muscle cells to the intima. In the rabbits treated with scoparone,
      there were fewer pathological morphology changes found in vascular segments than
      in the untreated hyperlipidaemic diabetic rabbits. 4. In the vascular reactivity
      experiments, the phenylephrine-induced contraction and nitroprusside induced
      dilatation did not differ significantly among the three rabbit groups, except
      that the contraction was enhanced in the thoracic aorta of hyperlipidaemic
      diabetic rabbits either untreated or treated withscoparone, as compared to the
      normal group, and the sensitivity to nitroprusside was increased in the thoracic
      aorta of the scoparone-treated group as compared to the untreated group.5. The
      endothelium-dependent dilatation induced by acetylcholine was significantly
      attenuated in both the aortic arch and thoracic aorta from the hyperlipidaemic
      diabetic rabbits as compared to the normal rabbits. This attenuation was
      partially prevented, when scoparone (5 mg kg-1) was administered daily.6. These
      results suggest that scoparone protects against some alterations of plasma
      lipoproteins,vascular morphology and vascular reactivity in the hyperlipidaemic
      diabetic rabbit. These protective effects of scoparone may be partly related to
      its free radical scavenging property.

PMID- 8306095
TI  - Role of prostaglandins and nitric oxide in acute inflammatory reactions in guinea
      pig skin.
AB  - 1. Oedema formation in skin is dependent on a synergism between mediators that
      increase vascular permeability and mediators that enhance local blood flow.
      Leukocyte accumulation is also enhanced by mediators that increase local blood
      flow. In this study, we have investigated whether nitric oxide (NO), an important
      endogenous vasodilator, could modulate oedema formation and leukocyte
      accumulation in guinea-pig skin. 2. Local administration of the NO synthesis
      inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), dose-dependently inhibited
      the oedema formation induced in response to intrademal injection of bradykinin or
      histamine. L-NAME, but not NG-nitro-D-arginine methyl ester (D-NAME); also
      inhibited oedema formation in response to i.d. injection of platelet-activating
      factor (PAF), zymosan-activated plasma (ZAP) and in a passive cutaneous
      anaphylactic (PCA) reaction. 3. N-iminoethyl-L-ornithine (L-NIO) was less
      effective and about 100 times less potent than L-NAME in inhibiting bradykinin
      induced oedema formation. The cyclo-oxygenase inhibitor, ibuprofen, had little
      effect on oedema responses induced by bradykinin, PAF and in a PCA reaction. On
      the other hand, histamine-induced oedema formation was significantly suppressed
      by ibuprofen. 4. The inhibition by L-NAME of bradykinin-induced oedema formation
      was reversed by co-injection of sodium nitroprusside (SNP) or prostaglandin E1
      (PGE1). 5. L-NAME inhibited 111In-eosinophil and 111In-neutrophil accumulation
      induced by i.d. injection of ZAP. 111In-eosinophil accumulation induced by PAF
      and in the PCA reaction was also inhibited by L-NAME but not by D-NAME. 6. Co
      injection of SNP or PGE1, reversed the inhibition by L-NAME of ZAP-induced oedema
      formation and 111In-neutrophil accumulation. SNP, but not PGE1, also reversed the
      effects of L-NAME on ZAP-induced 111In-eosinophil accumulation.7. L-NAME caused a
      significant decrease in basal cutaneous blood flow when injected alone or with
      bradykinin. Again, SNP or PGE, reversed the effects of L-NAME suggesting that the
      inhibitory action of L-NAME on oedema formation and cell accumulation was due to
      an inhibition of vasodilator tone in the microcirculation.8. Thus, it appears
      that in guinea-pig skin the inhibition of the production of endogenous NO
      inhibits both leukocyte accumulation and oedema formation induced by different
      mediators of inflammation.Since administration of L-NAME also causes a local
      decrease in basal blood flow, we suggest that this is the mechanism by which it
      exerts anti-inflammatory effects in this model.

PMID- 8306096
TI  - Evidence for functional dissociation of dependence and tolerance in guinea-pig
      isolated ileal segments following 20 hour exposure to morphine in vitro.
AB  - 1. In the present study we have examined the relationship between tolerance and
      dependence in isolated ileal segments from the guinea-pig under three different
      conditions: fresh preparations not previously exposed to morphine (fresh/morphine
      naive); preparations stored overnight at 4 degrees C in modified Krebs-Henseleit
      saline (overnight-stored/morphine-naive); preparations stored overnight at 4
      degrees C in Krebs-Henseleit saline containing 10 microM morphine and extensively
      washed with modified Krebs-Henseleit saline to remove residual morphine
      (overnight-stored/morphine-exposed). 2. Morphine produced a concentration
      dependent inhibition of the response of ileal segment to 0.1 Hz, 1 ms and 10 V
      transmural field stimulation in fresh/morphine-naive, overnight-stored/morphine
      naive and overnight-stored/morphine-exposed preparations. The maximum effect
      observed was similar in all three preparations-approximately 80% inhibition.
      Although, morphine was significantly more potent in the fresh/morphine-naive
      preparations (pD2 6.72 +/- 0.05, n = 8) than either the overnight-stored/morphine
      native (pD2 6.42 +/- 0.11, n = 8) or the overnight-stored/morphine-exposed (pD2
      6.44 +/- 0.14, n = 8), there was no significant difference between the overnight
      exposure to ileal segments to 10 microM morphine at 4 degrees C failed to induce
      tolerance to morphine. 3. The mu opiate receptor antagonist, naloxone (10
      microM), produced contractions in both fresh/morphine-naive and overnight
      stored/morphine-naive ileal segments following acute exposure to 10 microM
      morphine. Naloxone (10 microM) also produced contractions in 2/9 fresh/morphine
      naive, 1/9 overnight-stored/morphine-naive and 7/9 overnight-stored/morphine
      exposed preparations in the absence of morphine. The greater incidence of
      naloxone-induced contractions in overnight-stored/morphine-exposed
      preparations,suggests that dependence in this model is the product of adaptive
      changes that outlive the presence of morphine.4. The selective alpha2
      adrenoceptor agonists, clonidine (0.3 microM) and 5-bromo-6-[2-imidazolin-2
      ylamino]-quinoxaline bitartrate (UK-14304, 1 microM), inhibited naloxone-induced
      contractions in overnight-stored/morphine-exposed preparations of ileal segments
      (n = 4 preparations for each agonist), suggesting that the response is due to
      transmitter release from the myenteric plexus.5. The findings in the present
      study indicate that tolerance and dependence to morphine in ileal segments of the
      guinea-pig can be functionally dissociated by overnight exposure to morphine at 4
      degrees C.The development of tolerance to morphine, unlike dependence, appears to
      be a temperature-dependent process. This also raises the possibility that
      naloxone possesses intrinsic negative agonism at morphine sensitive receptors,
      which is manifested as a functional response only after adaptive changes in the
      myenteric plexus following exposure to morphine.

PMID- 8306097
TI  - Different pathways of calcium sensitization activated by receptor agonists and
      phorbol esters in vascular smooth muscle.
AB  - 1. It has been shown that receptor agonists and activators of protein kinase C,
      phorbol esters, increase Ca2+ sensitivity of contractile elements in vascular
      smooth muscle. To discover if protein kinase C is involved in the agonist
      mediated Ca2+ sensitization, we examined the effects of receptor agonists in the
      rat isolated aorta in which protein kinase C activity had been diminished by
      pretreatment with phorbol 12-myristate 13-acetate for 24 h. 2. In the aorta with
      protein kinase C activity, a high concentration (1 microM) of 12-deoxyphorbol 13
      isobutyrate induced contraction and a low concentration (100 nM) potentiated high
      K(+)-induced contraction. In addition, prostaglandin F2 alpha induced greater
      contractions than high K+ at a given cytosolic Ca2+ level. The maximally
      effective concentrations of noradrenaline and endothelin-1 also induced greater
      contraction than high K+. In the aorta without protein kinase C activity, the
      contraction induced by 12-deoxyphorbol 13-isobutyrate and its potentiation of the
      high K(+)-induced contraction were abolished. However, prostaglandin F2 alpha,
      noradrenaline and endothelin-1 still induced a greater contraction than high K+.
      3. In the aorta without protein kinase C activity, noradrenaline, endothelin-1
      and prostaglandin F 2 alpha, but not 12-deoxyphorbol 13-isobutyrate, induced
      contractions in the presence of the Ca2+ channel blocker, verapamil, or in the
      absence of external Ca2+, by increasing Ca2+ sensitivity. 4. In the permeabilized
      preparations, inhibition of protein kinase C activity abolished the effect of
      potentiation of the Ca(2+)-induced contraction by 12-deoxyphorbol 13-isobutyrate
      although the potentiation of the contraction by prostaglandin F2 alpha did not
      change. 5. These results suggest that there are two pathways for Ca2+
      sensitization in rat aorta; a protein kinase C-dependent pathway which is
      activated by phorbol esters, and a protein kinase C-independent pathway which is
      activated by receptor agonists.

PMID- 8306098
TI  - Regional haemodynamic responses to intravenous and intraarterial endothelin-1 and
      big endothelin-1 in conscious rats.
AB  - 1. In the same chronically-instrumented conscious Long Evans rats, we assessed
      regional haemodynamic responses to i.v. and i.a. injections of endothelin-1 (ET
      1) and big endothelin-1 at doses of 0.05 (n = 4) and 0.5 nmol kg-1 (n = 7). 2.
      For ET-1, the cardiovascular effects (initial hypotension and tachycardia with
      transient hindquarters vasodilation, followed by hypertension, bradycardia and
      renal, mesenteric and hindquarters vasoconstrictions) of i.v. and i.a. injections
      were not different. 3. Similarly, for big ET-1, the cardiovascular effects
      (hypertension, bradycardia and renal, mesenteric, and hindquarters
      vasoconstrictions) of i.v. and i.a. injections were not different. 4. At a dose
      of 0.5 nmol kg-1, i.v. or i.a., the pressor effects of ET-1 and big ET-1 were not
      different(area under curve [AUCO-30m.), ET-1 i.v. = 786 +/- 115 mmHg min; ET-1
      i.a. = 880 +/- 165 mmHg min;big ET-1 i.v. = 878 +/- 93 mmHg min; big ET-1 i.a. =
      833 +/- 103 mmHg min); but ET-1 caused greater renal, and lesser hindquarters,
      vasoconstrictions than big ET-1 (renal ET-1 i.v., AOC = 1550 +/- 211%min; ET-1
      i.a., AOC = 1746 +/- 139% min; big ET-1 i.v., AOC = 1097 +/- 128% min; big ET-1
      i.a.,AOC = 1041 +/- 119% min; hindquarters, ET-1 i.v., AOC = 758 +/- 176% min; ET
      1 i.a. AOC =787 +/- 184% min; big ET-1 i.v., AOC = 1270 +/- 88% min; big ET-1
      i.a., AOC = 1173 +/- 77% min), while the mesenteric vasoconstrictor effects of
      both peptides were not significantly different (ET-1 i.v.AOC = 1419 +/- 132% min;
      ET-l i.a., AOC = 1526 +/- 172% min; big ET-1 i.v., AOC = 1099 +/- 166%min; big ET
      1 i.a., AOC = 1155 +/- 120% min).5. Under the conditions of our experiments,
      pulmonary clearance of ET-1, or pulmonary activation of big ET-1, was not
      apparent from the haemodynamic responses to i.v. and i.a. administration of the
      peptides. The results are consistent with previous findings indicating that
      local, rather than systemic,conversion of exogenous big ET-1 to ET-1 is
      responsible for its regional haemodynamic actions.

PMID- 8306099
TI  - Relevance of the use of [3H]-clonidine to identify imidazoline receptors in the
      rabbit brainstem.
AB  - 1. [3H]-clonidine binding was investigated in membranes isolated from the ventral
      medulla oblongata of the rabbit, where clonidine produced a hypotensive effect
      which was not mediated by adrenoceptors. [3H]-clonidine specific binding, as
      defined by the difference between the binding of [3H]-clonidine in the presence
      and in the absence of 10 microM cirazoline, occurred at two sites: a high
      affinity site with a KD = 2.9 +/- 0.7 nM and a Bmax of 40 +/- 8 fmol mg-1 protein
      and a low affinity site with a KD = 18.2 +/- 0.4 nM and a Bmax of 66 +/- 14 fmol
      mg-1 protein. 2. The high affinity sites being catecholamine-sensitive were
      identified as alpha 2-adrenoceptors. The low affinity binding of [3H]-clonidine
      was insensitive to catecholamines, as well as to other alpha 2-adrenoceptor
      specific probes, and could be inhibited with high affinity only by compounds
      which lowered blood pressure when directly injected in the nucleus reticularis
      lateralis of the ventral brainstem, or by antagonists. 3. It was concluded that
      in the ventral medulla of the rabbit, [3H]-clonidine labelled alpha 2
      adrenoceptors and imidazoline receptors (IRs). Only the latter were related to
      the hypotensive effects of clonidine and rilmenidine directly injected into the
      rostroventrolateral medulla oblongata (RVLM) of the rabbit. The methodological
      problems regarding the study of IRs with [3H]-clonidine are discussed.

PMID- 8306100
TI  - Effects of selective antagonism of beta-adrenoceptor sub-types on responses to
      isoprenaline in rat distal colon in vitro.
AB  - 1. The effects of the beta 1- and beta 2-adrenoceptor selective antagonists, CGP
      20712A and ICI 118551 respectively, on responses to isoprenaline-induced
      relaxation of rat distal colon were investigated in order to determine the
      contributions of these subtypes to relaxation. In addition, the properties of ICI
      D7114, a novel putative stimulant of atypical beta-adrenoceptors, were
      investigated. Our preliminary experiments with ICI D7114 showed that this
      compound lacked agonist activity in rat distal colon and in fact antagonized
      responses to isoprenaline. We therefore studied the antagonism of isoprenaline by
      ICI D7114 in more detail. 2. Longitudinal segments of rat distal colon were
      suspended in Krebs solution at 37 degrees C for isometric recording. The Krebs
      solution contained EDTA (23 microM) and prazosin (0.1 microM) and was gassed with
      95/5% O2/CO2. After an initial equilibration period, reproducible contractions to
      a submaximal concentration of methacholine (1 microM) were obtained before
      carrying out a concentration-response curve (CRC) to isoprenaline in a non
      cumulative manner. Four consecutive CRCs to isoprenaline were carried out in each
      tissue with a 1 h interval between each curve. Antagonists were present in
      increasing concentrations during the intervals between CRCs. Control tissues
      received no antagonists to allow estimation of the magnitude of time-dependent
      changes. 3. Isoprenaline produced a concentration-dependent inhibition of
      methacholine-induced contractions. CRCs to isoprenaline were reproducible with no
      significant time-dependent changes. Propranolol produced no shift of the
      isoprenaline CRC at 0.01 microM and a 5 fold shift at 0.1 microM. No further
      shift was observed with 1 microM. CGP 20712A had no effect on the CRC to
      isoprenaline at 0.1, 1 and 3 microM. ICI118551 produced little or no shift at 0.1
      microM and a six fold shift with 1 microM. No further shift was observed with 3
      microM. ICI D7114 produced a concentration-dependent parallel rightward shift of
      the CRC to isoprenaline. Schild analysis gave a slope close to unity and a mean
      pA2 value of 7.29 for ICI D7114.4. The results with propranolol and ,l- and 132
      adrenoceptor antagonists confirm the mainly atypical nature of beta-adrenoceptors
      in rat distal colon. There may also be a small contribution from beta2
      adrenoceptors in the response to isoprenaline but beta1-adrenoceptors are absent.
      ICI D7114 has no agonist activity and behaves as a relatively high affinity
      reversible competitive antagonist of atypical beta-adrenoceptors in this
      preparation.

PMID- 8306101
TI  - Antagonism of levcromakalim by imidazoline- and guanidine-derivatives in rat
      portal vein: involvement of the delayed rectifier.
AB  - 1. In rat whole portal veins, guanabenz (100 nM to 10 microM) and antazoline (100
      nM to 100 microM) each increased the amplitude, frequency and duration of
      spontaneous contractions. In addition, guanabenz (30 microM) and antazoline (30
      microM) each antagonized the ability of levcromakalim (3 nM to 10 microM) to
      inhibit the spontaneous contractions of this tissue. 2. Whole-cell voltage-clamp
      recordings were made from freshly-isolated rat portal vein cells dispersed by a
      collagenase/pronase enzyme treatment. The ability of several agents (antazoline,
      cirazoline, clonidine, guanabenz and phentolamine, each containing an imidazoline
      or guanidine moiety), to modulate potassium (K) currents and to inhibit the
      actions of levcromakalim was investigated. 3. Antazoline, cirazoline, clonidine,
      guanabenz and phentolamine (each at a concentration of 30 microM) had little
      effect on control non-inactivating currents but inhibited the delayed-rectifier
      current, IK(V). 4. Levcromakalim (1 microM) induced a non-inactivating current,
      IK(ATP), and also inhibited the delayed rectifier current, IK(V). 5.
      Glibenclamide (1 microM) had no effect on control delayed rectifier or non
      inactivating currents, but it inhibited the simultaneous induction of IK(ATP) and
      reduction of IK(V) produced by levcromakalim (1 microM). 6. Antazoline,
      cirazoline, clonidine and guanabenz (each at a concentration of 30 microM)
      prevented the induction of IK(ATP) by levcromakalim (1 microM). Phentolamine (30
      microM) and clonidine (30 microM) each inhibited the IK(ATP) generated by
      levcromakalim (1 microM). 7. It is concluded that a variety of agents which
      possess either an imidazoline (antazoline, cirazoline, clonidine and
      phentolamine) or a guanidine (guanabenz) moiety within their structure inhibit
      the delayed rectifier current, IK(V). This action may thus be mediated via a so
      called non-adrenoceptor imidazoline binding site. Furthermore, the ability of
      these ligands to inhibit IK(V) and to antagonize both the induction of IK(ATP)
      and the vasorelaxation produced by levcromakalim is consistent with the view that
      the channel (KATP) which underlies IK(ATP) is a voltage-insensitive state of the
      delayed rectifier K-channel (Kv).

PMID- 8306102
TI  - The effect of defibrotide on thromboembolism in the pulmonary vasculature of mice
      and rabbits and in the cerebral vasculature of rabbits.
AB  - 1. Administration of bovine thrombin (100 u kg-1) into the carotid artery of
      rabbits induces a sustained accumulation of 111 Indium-labelled platelets within
      the cranial vasculature over the subsequent 3 h. 2. Intracarotid (i.c.)
      administration of defibrotide (64 mg kg-1 bolus plus 64 mg kg-1 h-1 for 1 h)
      prior to i.c. thrombin (100 u kg-1) significantly reduces the ability of thrombin
      to induce cranial thromboembolism in rabbits. 3. Intravenous (i.v.)
      administration of thrombin (20 u kg-1) in rabbits induces a reversible
      accumulation of radiolabelled platelets into the thoracic circulation which is
      significantly reduced by i.v. administration of defibrotide (64 mg kg-1 bolus
      plus 64 mg kg-1 h-1 for 1 h) prior to i.v. thrombin. In contrast, platelet
      accumulation in response to adenosine diphosphate (ADP; 20 micrograms kg-1, i.v.)
      or platelet activating factor (PAF; 50 ng kg-1, i.v.) is not significantly
      affected by this treatment. 4. Intravenous administration of the nitric oxide
      (NO)-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg kg-1)
      potentiates platelet accumulation induced by low dose thrombin (10 u kg-1, i.v.)
      within the pulmonary vasculature of rabbits. The potentiated response is
      significantly abrogated following pretreatment with defibrotide (64 mg kg-1 bolus
      plus 64 mg kg-1 h-1 for 1 h, i.v.). 5. Intravenous injection of human thrombin
      (1250 u kg-1) to mice induces death within the majority of animals which is
      significantly reduced by pretreatment with defibrotide (150-175 mg kg-1, i.v.).
      In contrast, death induced by i.v. collagen (1.25 mg kg-1) plus adrenaline (75
      microg kg-1) is not significantly affected by defibrotide pretreatment.6. The
      inhibitory effect of defibrotide in mice is abolished following concomitant
      treatment with the inhibitor of fribrinolysis, tranexamic acid (100 mg kg-1,
      i.v.), but is unaffected following treatment with the cyclo-oxygenase inhibitor,
      aspirin (300 mg kg-1, i.p.).7. The protective effect of defibrotide against
      thrombin-induced thromboembolism in the mouse is potentiated by recombinant
      tissue-plasminogen activator (rt-PA; 1 mg kg-1, i.v.) or unfractionated heparin
      (10 u kg-1, i.v.) administration.8. The results suggest that defibrotide may
      possess antithrombotic activity on thrombin-induced thromboembolism which, at
      least in the mouse, may be partially mediated via induction of the fibrinolytic
      pathway.

PMID- 8306103
TI  - 5-HT4 receptor mediated facilitation of the emptying phase of the peristaltic
      reflex in the guinea-pig isolated ileum.
AB  - 1. The influence of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists
      on the emptying phase (circular muscle contraction) of the peristaltic reflex was
      investigated in the guinea-pig isolated ileum. 2. The effect of drug application
      to the serosal surface was measured as the changes in threshold pressure required
      to trigger the peristaltic reflex and the interval between the peristaltic
      strokes. A facilitation or inhibition of peristalsis was defined as a reduction
      or increase in threshold pressure respectively. 3. Peristalsis was not modified
      by the inclusion of methysergide (1 microM) and/or ondansetron (2 microM) in the
      bathing medium. 5-HT (0.1-1.0 microM) caused a facilitation of the peristaltic
      reflex; the response curve to 5-HT was not altered by the presence of
      methysergide (1 microM) and ondansetron (2 microM). 4. In the presence of
      methysergide (1 microM) plus ondansetron (2 microM), 5-HT (7.36 +/- 0.06), 5
      methoxytryptamine (7.01 +/- 0.17), 5-carboxamidotryptamine (5.43 +/- 0.06),
      renzapride (6.09 +/- 0.17), (S)-zacopride (5.99 +/- 0.11), (R)-zacopride (5.61 +/
      0.13) and metoclopramide (4.8 +/- 0.65) caused a concentration-related
      facilitation of the peristaltic reflex, the pEC50 values (mean +/- s.e.mean)
      being shown in parentheses. 2-Methyl-5-HT was ineffective up to 10 microM. 5. The
      administration of SDZ 205-557 (1 microM) alone failed to modify the peristaltic
      reflex, but caused a parallel dextral shift in the concentration-effect curve to
      5-HT (apparent pKB 7.38 +/- 0.30). It failed to modify the effect of
      acetylcholine to enhance the peristaltic reflex. 6. It is concluded that the rank
      order of potency of the 5-HT agonists from the indole and substituted benzamide
      series to facilitate the emptying phase of the peristaltic reflex in the guinea
      pig ileum closely correlates with their published actions as 5-HT4 agonists in
      other systems. An agonist action on the 5-HT4 receptor is also supported by the
      potency of the 5-HT3/5-HT4 antagonist SDZ 205-557 (but not the 5-HT3 antagonist
      ondansetron) to inhibit the effects of 5-HT.

PMID- 8306104
TI  - Electrophysiological and antiarrhythmic actions of the kappa agonist PD 129290,
      and its R,R (+)-enantiomer, PD 129289.
AB  - 1. The S,S (-)-enantiomer PD 129290, a kappa agonist, and its corresponding
      inactive R,R (+)-enantiomer (PD 129289) were studied in rat isolated hearts and
      in intact rats for cardiovascular and antiarrhythmic actions. The
      electrophysiological actions of PD 129290 were also studied in rat isolated
      cardiac myocytes using voltage clamp. 2. Ventricular pressure, heart rate and ECG
      were studied in isolated hearts while blood pressure, heart rate and ECG were
      studied in pentobarbitone-anaesthetized rats. In the latter, responses to
      electrical stimulation and coronary occlusion were also investigated. 3. In
      isolated hearts both enantiomers, over the concentration range 2-16 microM, dose
      dependently reduced systolic ventricular pressure and heart rate while prolonging
      the P-R and QRS intervals of the ECG. 4. At doses of 1-32 mumol kg-1 both
      enantiomers reduced blood pressure and heart rate in anaesthetized rats. In
      addition, both enantiomers increased the size of the RSh and increased P-R, QRS,
      and Q-T intervals of the ECG. The thresholds for premature beats and ventricular
      fibrillation were dose-dependently increased by PD 129289. At lower doses PD
      129290 decreased thresholds. These decreases were blocked by naloxone to reveal
      underlying increases similar to those seen with PD 129289. Both enantiomers
      increased refractory periods. 5. Naloxone (8 mumol kg-1) did not alter any of the
      actions of PD 129290, except to abolish the initial decreases in thresholds in
      intact rats seen with lower doses of PD 129290. 6. Both enantiomers (2 and 8
      mumol kg-1) equally reduced arrhythmias in anaesthetized rats subject to
      occlusion of a coronary artery. 7. In rat isolated cardiac myocytes 20 microM PD
      129290, in the presence and absence of naloxone decreased the amplitude of the
      transient sodium current by about 50% without affecting the voltage dependence of
      activation or inactivation of this current.8. The antiarrhythmic actions of both
      enantiomers appear to primarily result from their Class I(sodium channel
      blockade) properties which are independent of kappa agonism.

PMID- 8306105
TI  - GABAB receptors modulate catecholamine secretion in chromaffin cells by a
      mechanism involving cyclic AMP formation.
AB  - 1. The function of gamma-aminobutyric acidB (GABAB) receptors in modulation of
      catecholamine secretion by chromaffin cells and the possible mechanism involved
      in this action have been examined. 2. The GABAB agonists (-)-baclofen and 3
      aminopropylphosphinic acid (3-APPA) were found to induce a dose-dependent
      increase of basal catecholamine secretion. The EC50s were 151 +/- 35 microM and
      225 +/- 58 microM for baclofen and 3-APPA, respectively. This stimulatory effect
      was specific since it could be blocked by 0.5 mM of the specific GABAB antagonist
      CGP-35348. 3. In contrast, preincubation of chromaffin cells with the GABAB
      agonists was found to inhibit, in a dose-dependent manner, the catecholamine
      secretion evoked by 10 microM nicotine and 200 microM muscimol. 4. The effects of
      GABAB agonists on both basal and evoked catecholamine secretion were found to be
      accompanied by parallel changes in intracellular calcium concentration ([Ca2+]i).
      GABAB agonists produced a dose-dependent increase in [Ca2+]i which was partially
      blocked by CGP 35348, but they produced a strong inhibition of the [Ca2+]i
      increase induced by nicotine and muscimol. 5. The GABAB agonists also produced a
      dose-dependent increase in intracellular cyclic AMP levels, there being a direct
      correlation between both increase in catecholamine secretion and in intracellular
      cyclic AMP levels. 6. The pretreatment of chromaffin cells with pertussis toxin
      doubled the catecholamine secretion and increased by four times the intracellular
      cyclic AMP levels evoked by GABAB agonists. 7. The possible involvement of
      adenylate cyclase in the mechanism of GABAA receptor modulation of catecholamine
      secretion is discussed.

PMID- 8306106
TI  - The guinea-pig distal colon--a sensitive preparation for the investigation of 5
      HT4 receptor-mediated contractions.
AB  - 1. Experiments were designed to characterize pharmacologically the contractile
      responses to 5-hydroxytryptamine (5-HT) in the guinea-pig isolated distal colon
      longitudinal muscle-myenteric plexus preparation (LMMP). 2. In the presence of
      methiothepin (100 nM) and granisetron (1 microM), 5-HT (10 pM-10 nM) produced
      concentration-dependent contractile responses of the guinea-pig distal colon
      LMMP, with a pEC50 of 9.2 +/- 0.08. 3. Responses to 5-HT were mimicked by a
      series of tryptamine analogues, with the following rank order of potency; 5-HT >
      5-MeOT >> 5-CT > tryptamine > 2-Me-5-HT. All were found to be full agonists. 4.
      Responses to 5-HT were also mimicked by a series of substituted benzamide
      analogues. Their rank order of potency was 5-HT > renzapride > cisapride > (S)
      zacopride > (R)-zacopride > metoclopramide. All were full agonists relative to 5
      HT. 5. The benzimidazolone derivatives, BIMU 1 and BIMU 8 were approximately
      equipotent partial agonists (intrinsic activities of 0.8 +/- 0.07 and 0.5 +/-
      0.08 respectively) in the guinea-pig distal colon. 6. Tropisetron produced a
      rightward displacement of the 5-HT concentration-effect curve, yielding an
      apparent pA2 of 6.4 +/- 0.1. The slope of the Schild plot (1.3 +/- 0.1) was
      significantly greater than unity. 7. SDZ 205,557 produced a concentration
      dependent shift to the right of the 5-HT concentration-response curve, yielding
      an estimated pA2 of 7.8 +/- 0.1 and a slope which did not significantly deviate
      from unity. SDZ 205 557 produced similar pKB estimates (7.3-7.9) when tested
      against 5-MeOT,renzapride and 5-CT, indicating a common site of action.8. The
      pharmacological profile of the 5-HT-evoked contractions of the guinea-pig distal
      colon LMMPare consistent with activity at the 5-HT4 receptor. Furthermore, of the
      models of this receptor described in the literature, the guinea-pig distal colon
      appears to be the most sensitive model to date, making it a useful tool in the
      investigation of 5-HT4 receptor-mediated events.

PMID- 8306107
TI  - ZD1542, a potent thromboxane A2 synthase inhibitor and receptor antagonist in
      vitro.
AB  - 1. The thromboxane A2 synthase (TXS) inhibitory activity and the thromboxane A2
      (TP)-receptor blocking action of ZD1542 (4(Z)-6-[2S,4S,5R)-2-[1-methyl-1-(2-nitro
      4-tolyloxy)ethyl]-4-(3- pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid) has been
      evaluated in vitro on platelets and whole blood from a range of species including
      man. Antagonist activity has also been investigated in vascular and pulmonary
      smooth muscle preparations in vitro. 2. ZD1542 caused concentration-dependent
      inhibition of human platelet microsomal thromboxane B2 (TXB2) production in vitro
      (IC50 = 0.016 microM); this inhibition was associated with an increase in
      prostaglandin E2 (PGE2) and PGF2 alpha formation. 3. ZD1542 also inhibited
      collagen-stimulated TXS in human, rat and dog whole blood giving IC50 values of
      0.018, 0.009 and 0.049 microM respectively. The drug did not modify platelet
      cyclo-oxygenase activity as inhibition of TXB2 formation was associated with a
      concomitant increase in the levels of PGD2, PGE2 and PGF2 alpha. ZD1542 had
      little if any effect against cultured human umbilical vein endothelial cell
      (HUVEC) cyclo-oxygenase (IC50 > 100 microM) and prostacyclin (PGI2) synthase
      (IC50 = 18.0 +/- 8.6 microM). 4. ZD1542 caused concentration-dependent inhibition
      of U46619-induced aggregation responses of human, rat and dog platelets yielding
      apparent pA2 values of 8.3, 8.5 and 9.1 respectively. The drug was selective as,
      at concentrations up to 100 microM, it did not modify 5-hydroxytryptamine (5-HT)
      or the primary phases of adenosine diphosphate (ADP) and adrenaline-induced
      aggregation. Furthermore, ZD1542 (100 microM) modified only weakly the platelet
      effects of PGD2, PGE1 and PGI2. 5. ZD1542 also caused concentration-dependent
      inhibition of U46619-mediated contractions of rat thoracic aorta, guinea-pig
      trachea and lung parenchyma preparations giving apparent pA2 values of 8.6,8.3
      and 8.5 respectively. At concentrations approaching three orders of magnitude
      greater than those required to block U46619-mediated contractions, the drug did
      not affect the actions of non-prostanoid agonists or exhibit agonist activity in
      any of the smooth muscle preparations employed; neither did it interact at EP- or
      FP-receptors.6. In conclusion, the present study demonstrates that ZD1542 is a
      drug that exhibits both potent,selective TXS inhibition and TXA2 receptor
      antagonism.

PMID- 8306108
TI  - Antinociceptive activity of NK1 receptor antagonists: non-specific effects of
      racemic RP67580.
AB  - 1. Release of substance P in the dorsal horn is considered a primary event in the
      perception of pain. The profile of racemic RP67580, a non-peptide antagonist at
      the NK1 (substance P) receptor, was examined in a range of antinociception tests
      on rodents. 2. At doses up to 30 mg kg-1, s.c. racemic RP67580 exhibited
      antinociceptive activity in writhing and formalin paw tests in mice and gerbils.
      Acetic acid induced writhing and the licking response to formalin were reduced to
      40-50% of the level observed in vehicle-treated animals (P < 0.05). However, this
      agent was not active in mouse tail flick, rat paw pressure or rat and guinea-pig
      formalin paw tests. 3. Like racemic RP67580, the calcium channel blockers
      nifedipine (30 mg kg-1, i.p.) and verapamil (10 or 20 mg kg-1, s.c.) inhibited
      the response to formalin by approximately 60% in gerbils (P < 0.05 compared with
      vehicle-treated animals). 4. Evidence for calcium channel antagonist activity of
      RP67580 was obtained in vitro. Racemic RP67580 inhibited calcium entry into
      depolarized strips of guinea-pig ileum longitudinal muscle myenteric plexus
      (apparent KB = 587 +/- 115 nM), inhibited [3H]-diltiazem binding to rabbit
      skeletal membranes (IC50 = 298 nM) and depressed high threshold calcium currents
      in neurones cultured from rat cortex (10% inhibition at 10 microM). 5. These
      findings indicate that the acute antinociceptive effects of RP67580 may not be
      attributable to a specific interaction with NK1 receptors and may be mediated via
      calcium channel blockade.

PMID- 8306109
TI  - Evidence that RU 24969-induced locomotor activity in C57/B1/6 mice is
      specifically mediated by the 5-HT1B receptor.
AB  - 1. The behavioural effects of the 5-HT1B receptor agonists, RU 24969 and CGS
      12066B, have been investigated in C57/B1/6 mice. 2. RU 24969 (1-30 mg kg-1)
      produced intense and prolonged hyperlocomotion and other behavioural changes. 3.
      CGS 12066B caused similar effects, but they were much less pronounced,
      inconsistent and transient irrespective of whether this drug was given i.p. (1-15
      mg kg-1) or i.c.v. (0.2-40 micrograms). However, CGS 12066B (7.5 and 15 mg kg-1)
      caused a dose-related inhibition of RU 24969 (7.5 mg kg-1)-induced
      hyperlocomotion indicating that the former is a 5-HT1B partial agonist. 4. RU
      24969 (7.5 mg kg-1 i.p.)-induced hyperlocomotion was inhibited by the (-)-, but
      not (+)-isomers of pindolol (4 mg kg-1) and propranolol (20 mg kg-1) but not by
      metoprolol (10 mg kg-1) or ICI 118,551 (5 mg kg-1), consistent with an
      involvement of 5-HT1A or 5-HT1B receptors. 5. The response was not altered by the
      selective 5-HT1A receptor antagonist, WAY 100135 (5 mg kg-1, s.c.), the 5-HT2A/5
      HT2C receptor antagonist, ritanserin (0.1 mg kg-1), the selective 5-HT3 receptor
      antagonist, ondansetron (1 mg kg-1) or the non-selective 5-HT receptor
      antagonists methysergide (3 mg kg-1) and metergoline (3 mg kg-1). 6. Although
      spiroxatrine (0.1 mg kg-1) and ketanserin (1 mg kg-1) inhibited RU 24969-induced
      hyperlocomotion, these effects were probably due to antagonism of dopamine D2
      receptors and alpha 1-adrenoceptors respectively. 7. Taken together, these
      results indicate that RU 24969-induced hyperlocomotion results specifically from
      activation of central 5-HTIB receptors.8. Lesioning of 5-HT neurones with 5,7
      dihydroxytryptamine (75 microg, i.c.v.) or depletion with
      pchlorophenylalanine(200 mg kg-1, i.p. for 14 days) had no effect on RU 24969
      induced hyperlocomotiondemonstrating that the 5-HTIB receptors involved are
      postsynaptic and that they do not show super sensitivity.9. The involvement of
      other monoamine neurotransmitter systems in RU 24969-induced hyperlocomotionwas
      also examined. The response was inhibited by the al-adrenoceptor antagonist,
      prazosin(1 mg kg-1), the dopamine DI receptor antagonist, SCH 23390 (0.05 mg kg
      1) and the dopamine D2 receptor antagonist, BRL 34778 (0.03 mg kg-1), but not by
      the M2-adrenoceptor antagonist, idazoxan(1 mg kg-1). Lesioning noradrenergic
      neurones with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine(100 mg kg-1) markedly
      attenuated this behaviour. These results show that the hyperlocomotion is
      expressed via noradrenergic and dopaminergic neurones acting on alpha 1
      adrenoceptors, DI and D2 receptors.10. RU 24969 decreased brain concentrations of
      5-hydroxyindoleacetic acid whilst simultaneously increasing 5-HT, consistent with
      the reduction of 5-HT neuronal activity by activation of 5-HTlA and 5-HTIB
      autoreceptors. RU 24969 increased brain 3-methoxy-4-hydroxyphenylglycol, but not
      noradrenaline, concentrations which supports the involvement of noradrenergic
      neurones in the expression of hyperlocomotion. RU 24969 did not alter dopamine,
      dihydroxyphenylacetic acid or homovanillic acid concentrations in the nucleus
      accumbens suggesting that the dopaminergic neurones terminating there are not
      directly involved.

PMID- 8306110
TI  - Mediation of the hypotensive action of systemic clonidine in the rat by alpha 2
      adrenoceptors.
AB  - 1. During the past few years it has been shown that the sympatholytic effect
      resulting from localized microinjection of clonidine and other imidazolines into
      the rostral ventrolateral medulla (RVL) results from activation of 'imidazoline'
      receptors (I1 receptors) rather than from an alpha 2-adrenoceptor-mediated
      effect. 2. The relative contributions of these two receptor systems to the
      hypotensive action of systemically administered clonidine have not been studied.
      Clonidine has affinity for both I1 and alpha 2-adrenoceptors; guanabenz
      represents a useful pharmacological tool, since it activates only the alpha 2
      adrenoceptor. 3. Antagonists acting at both I1 and alpha 2-adrenoceptors
      (idazoxan) and at only alpha 2-adrenoceptors (SK&F 86466; 6-chloro-3-methyl
      2,3,4,5-tetrahydro-3-benzazepine) are available. Idazoxan (1 mg kg-1, i.v.) and
      SK&F 86466 (3 mg kg-1, i.v.) produced an equivalent degree of blockade of the
      pressor response to guanabenz or clonidine in the pithed rat, a response mediated
      by the alpha 2-adrenoceptor. 4. Guanabenz (30 micrograms kg-1, i.v.) and
      clonidine (10 micrograms kg-1, i.v.) lowered blood pressure in the chloralose
      anaesthetized spontaneously hypertensive rat by 48 +/- 4.6 mmHg and 44 +/- 5.4
      mmHg, respectively; this response, for either agonist, was blocked by both
      idazoxan and SK&F 86466. 5. These data show that the hypotensive effect of
      intravenously administered clonidine results from activation of central alpha 2
      adrenoceptors, with no significant contribution from an I1-mediated effect. Thus
      clonidine can lower blood pressure by different receptor mechanisms, dependent on
      the route of administration.

PMID- 8306111
TI  - Insulin-mediated sensitization of adenylyl cyclase activation.
AB  - 1. Insulin may be an important regulator of vascular function. We have previously
      studied lymphocyte beta-adrenoceptors as a model for the human vascular beta
      adrenoceptor. To examine the effects of insulin on human beta-adrenoceptor
      responsiveness, adenylyl cyclase activity, cyclic AMP-dependent protein kinase
      activity and beta-adrenoceptor radioligand binding assays were performed on
      permeabilized mononuclear leukocytes. 2. With acute exposure to insulin in vitro,
      followed by washing and permeabilization there was a dose-dependent increase in
      both lymphocyte NaF-stimulated activity and beta-adrenoceptor-stimulated adenylyl
      cyclase activity paralleling an increase in beta-adrenoceptor-stimulated protein
      kinase A activity. Manganese-, forskolin- and forskolin plus
      guanylimidodiphosphate-stimulated adenylyl cyclase activities were not altered by
      insulin pretreatment. Additionally, mononuclear leukocyte beta-adrenoceptor
      density, proportion of externalized receptors and receptor affinity for agonist
      were not altered. 3. The data indicate that acute exposure to insulin sensitizes
      G-protein-stimulated adenylyl cyclase activity. These findings suggest a
      potential role for insulin in the regulation of beta-adrenoceptor responsiveness
      in man.

PMID- 8306112
TI  - Soviet special psychiatric hospitals. Where the system was criminal and the
      inmates were sane.
AB  - The subversion of psychiatric intervention for political purposes in the USSR
      during the 1970s and 1980s resulted in both intra-psychic and subsequent
      adaptational dysfunction in those dissidents who physically survived it.
      Incarceration in special psychiatric hospitals subjected the inmates to a sense
      of helplessness under the control of a malevolent power, futility, despair,
      danger from close and contentious contact with hardened criminals and the
      violently insane, overdosage with mind-altering and body-distorting neuroleptic
      drugs, and a Kafkaesque ambiguity concerning the specific terms of
      instutionalisation. Discharge did not bring release from continued threats and
      the eroded social networks to which the inmates returned subjected them to a new
      set of stressors. While some families remained intact and provided necessary
      support during the re-entry period, many families had been destroyed either by
      the circumstances of the family member's incarceration or by the length of the
      victim's stay in the psychiatric hospital. Wives left, people died, friends
      deserted, jobs evaporated, and often there was not even a home to accept them.
      Social agencies were either hostile or indifferent to their plight. Many felt
      like they had been thrown overboard from a prison ship without a life preserver.
      It was the proverbial transition from the frying pan into the fire.

PMID- 8306113
TI  - Childhood sexual abuse and mental health in adult life.
AB  - The relationship between childhood sexual abuse and mental health in adult life
      was investigated in a random community sample of women. There was a positive
      correlation between reporting abuse and greater levels of psychopathology on a
      range of measures. Substance abuse and suicidal behaviour were also more commonly
      reported by the abused group. Childhood sexual abuse was more frequent in women
      from disrupted homes as well as in those who had been exposed to inadequate
      parenting or physical abuse. While elements in the individual's childhood which
      increased the risks of sexual abuse were also directly associated to higher rates
      of adult psychopathology, abuse emerged from logistic regression as a direct
      contributor to adult psychopathology. Severity of abuse reported was related to
      the degree of adult psychopathology. The overlap between the possible effects of
      sexual abuse and the effects of the matrix of disadvantage from which it so often
      emerges were, however, so considerable as to raise doubts about how often, in
      practice, it operates as an independent causal element. Further, many of those
      reporting childhood sexual abuse did not show a measurable long-term impairment
      of their mental health. Abuse correlated with an increased risk for a range of
      mental health problems, but in most cases its effects could only be understood in
      relationship to the context from which it emerged.

PMID- 8306114
TI  - Otago Women's Health Survey 30-month follow-up. I: Onset patterns of non
      psychotic psychiatric disorder.
AB  - Women who showed new psychiatric morbidity after a 30-month follow-up of a random
      community sample of New Zealand women were compared with those who were free of
      psychiatric disorder at follow-up. There were 25 new cases among the 215 women
      who were originally not psychiatric cases and who were re-interviewed. Using the
      weighted back population data to obtain prevalence figures for the general
      population, 6.9% became new cases over the two and a half years. Those who
      developed psychiatric disorder initially showed more psychiatric symptoms at a
      subdiagnostic level. Baseline factors that preceded the onset of psychiatric
      disorder were being separated or divorced, coming from a large family, having
      poor social networks, living alone, having few social role responsibilities such
      as paid employment or motherhood, and having poor physical health. An additional
      cross-sectional association at follow-up was poor financial security. Good social
      networks were closely linked with the number of a woman's social roles and
      appeared to protect her against the onset of psychiatric disorder. Consistent
      with the initial cross-sectional study, the follow-up data provide no support for
      marriage and child-care being risk factors for female psychiatric disorder.
      However, in New Zealand, these factors indicate social integration and are
      associated with superior mental health.

PMID- 8306115
TI  - Otago Women's Health Survey 30-month follow-up. II: Remission patterns of non
      psychotic psychiatric disorder.
AB  - The follow-up phase of a random community sample of New Zealand women contrasted
      the social, demographic, and clinical characteristics of those women whose
      initial psychiatric disorder had remitted with those who continued to describe
      significant psychiatric morbidity, two-and-a-half years later. Of 272 women
      studied at baseline and reinterviewed, 57 had originally been psychiatric cases.
      Twenty-five of those women (44%) were still cases at follow-up. Using figures
      that statistically reconstructed the original population from the stratified
      sample, the remission rate in the parent population was 61% over the two-and-a
      half years (an average of 24% per annum). Women less likely to experience
      remission of their psychiatric disorder were of mid-age (45-64 years), with poor
      finances and with poor social relationships at the initial assessment. Although
      the age finding replicates a previous report from an Epidemiological Catchment
      Area study, it is not clear whether it is a universal relationship, true for all
      cultures. The alterations in social roles faced by women after child-rearing is a
      possible explanation, at least for New Zealand.

PMID- 8306116
TI  - Do psychosocial factors influence outcome in severely depressed female
      psychiatric in-patients?
AB  - Fifty-nine women admitted to hospital because of severe depression were studied
      prospectively during hospital admission and nine months following hospital
      discharge in order to identify psychosocial and illness factors associated with
      prognosis. Outcome was measured in terms of both depression scores and recovery
      at the time of follow-up. In keeping with the findings of other studies, the
      outcome was often poor, with only 54% having recovered nine months after
      discharge, poorer outcome being associated with more negative self-esteem
      measured when the women were depressed and with suicidal ideas. The findings
      indicate that in severely depressed women likely to be admitted to hospital,
      psychosocial factors may have less relevance to outcome, at least in the short
      term, than in less severely depressed patients studied in community or out
      patient samples.

PMID- 8306117
TI  - Self-esteem in recovered bipolar and unipolar out-patients.
AB  - The hypothesis of a low self-esteem in depressive patients was tested using the
      Rosenberg Self-Esteem Scale in 24 recovered unipolar and 27 recovered bipolar
      patients, compared with a normal control group of 26 subjects matched for age and
      sex. The hypothesis was confirmed only for unipolars; bipolar patients presented
      a self-esteem score not significantly different from normal scores. Self-esteem
      was not related to clinical characteristics of the affective disorder, suggesting
      that low self-esteem may be a basic component of a depression-prone personality.
      The investigation of the relationship between self-esteem and social adjustment
      confirmed the presence of social conformism in bipolar patients and rigidly set
      low self-esteem in unipolar patients. These results should stimulate the
      evaluation of different psychotherapeutic treatments in the long-term
      psychosocial management of affectively ill patients.

PMID- 8306118
TI  - The role of gender in understanding the familial transmission of schizoaffective
      disorder.
AB  - The purpose of this study was to test the effect of gender on the familial risk
      for schizophrenia and affective disorders in probands with schizoaffective
      disorder. The sample consisted of 42 DSM-III schizoaffective probands and 149
      first-degree relatives from the retrospective cohort family studies, the Iowa 500
      and non-500. Survival analysis estimated differences in morbidity risks, analysed
      by sex of proband and of relative. Findings showed that, among probands,
      relatives of females had significantly higher rates of schizophrenia and unipolar
      disorder than relatives of males. Further, among relatives, males were at
      significantly higher risk for schizophrenia spectrum disorders than females.
      Results were similar when probands were subdivided into their primary symptom
      patterns, that is 'mainly schizophrenic' or 'mainly affective', as well as by
      'schizoaffective, depressed' or 'schizoaffective, manic'. Implications for the
      taxonomy of schizoaffective disorder suggest a stronger relationship with
      schizophrenia, although the relationship with affective disorder remains unclear.

PMID- 8306119
TI  - Negative features, retrieval processes and verbal fluency in schizophrenia.
AB  - Twenty chronic schizophrenic patients, ten matched normal controls and nine
      depressed controls performed categorical verbal fluency tasks for three minutes
      each on five separate occasions. On each occasion the schizophrenic patients
      generated significantly fewer words than the controls. Comparison of the
      different occasions showed that the schizophrenic patients had as many words
      available in their inner lexicons but were inefficient in retrieving them. The
      schizophrenic patients also generated fewer clusters of related words and more
      words outside the specified category. Reduced ability to generate words while the
      lexicon remained intact was more marked in patients with negative features.
      Patients with incoherence, in contrast, were more likely to produce inappropriate
      words. We propose that both poverty of speech and incoherence of speech reflect
      problems in the retrieval of words from the lexicon. To cope with these problems
      patients with poverty of speech terminate their search prematurely while the
      patients with incoherence commit errors in selecting words for output.

PMID- 8306120
TI  - Personality disorders in patients with somatisation disorder. A controlled study.
AB  - Twenty-five women with somatisation disorder (SD) were compared with matched
      patient controls for the presence of personality disorders. Personality was
      assessed with the Personality Assessment Schedule (PAS). Interviewers were
      unaware of the patients' diagnoses. All controls had DSM-III-R axis I diagnoses
      of depressive or anxiety disorders. The prevalence of personality disorders among
      patients with somatisation disorder was 72% compared with 36% among controls.
      Certain personality disorders, including passive-dependent, histrionic, and
      sensitive-aggressive, occurred significantly more often in the SD patients than
      controls.

PMID- 8306121
TI  - A study of psychiatric morbidity in patients with Huntington's disease, their
      relatives, and controls. Admissions to psychiatric hospitals in Denmark from 1969
      to 1991.
AB  - Psychiatric morbidity among 74 non-affected first-degree relatives and 93 non
      affected second-degree relatives of patients with Huntington's disease (HD) was
      compared with that of 37 patients with HD and with matched control groups. Due to
      specific age criteria, the first-degree relatives were at decreased risk and the
      second-degree relatives at negligible risk of being carriers of the gene for HD.
      Information on admissions to departments of psychiatry and diagnoses at discharge
      were obtained for all subjects from a nationwide central register. Psychiatric
      morbidity was no greater among relatives than among controls, whereas HD patients
      had significantly more admissions and psychiatric diagnoses than relatives.
      Growing up with a risk of developing HD does not itself increase the risk of
      developing psychiatric illness resulting in hospital admission. Severe
      psychiatric disorders in HD patients were thus most likely to be aetiologically
      related to the disease process, possibly through a genetic mechanism.

PMID- 8306122
TI  - Psychosis and cannabis abuse in The Gambia. A case-control study.
AB  - Cannabis abuse is a major public health problem in The Gambia and other parts of
      West Africa, and the rise in the incidence of psychotic illness reflects the
      increased background use of cannabis by the local population. A case-control
      study was performed to determine the association between psychosis and cannabis
      abuse in The Gambia and the importance of other risk factors. Out of 234 patients
      admitted to Campama Psychiatric Unit over 12 months, 210 (90%) were enrolled in a
      case-control study. Urine was tested for cannabinoid substances and 38% were
      positive compared with 12% of matched non-psychotic control subjects. Analysis of
      the matched pairs showed that a positive urinary cannabinoid test, cigarette
      smoking, alcohol consumption, travel to Europe and family history of mental
      illness were all significant risk factors for psychotic illness; Koranic
      education reduced the risk. There was a positive correlation among the psychotic
      patients between a positive urinary cannabinoid test and the use of alcohol,
      ataya tea and cigarette smoking; a family history of mental illness showed a
      negative correlation.

PMID- 8306123
TI  - Psychiatric morbidity in sentenced segregated HIV-positive prisoners.
AB  - In this comparative study with a control group of prisoners, psychiatric
      morbidity was measured in two groups of sentenced prisoners, each group
      completing the GHQ-30 and 21-item Beck Depression Inventory (BDI). Group 1
      consisted of 40 segregated HIV-positive prisoners and group 2 a matched control
      group in the main prison who had no history of HIV seropositivity. All members of
      group 1 had a history of intravenous drug abuse. The mean GHQ-30 and BDI scores
      were significantly higher in group 1, and 90% of group 1 were psychiatric 'cases'
      compared with just over 42% of group 2. Levels of psychiatric morbidity present
      in a third group, consisting of HIV-positive prisoners who had not been
      segregated (prison authorities were unaware of their seropositivity) are an
      interesting pointer for further research.

PMID- 8306124
TI  - Stress among police body handlers. A long-term follow-up.
AB  - Thirty-five police officers were followed up three years after they had been
      first assessed following their involvement in the retrieval and identification of
      human remains after a major disaster. Most of these officers were free from signs
      of psychiatric morbidity. Organisational and managerial practices appear to be
      powerful antidotes to adverse post-traumatic reactions. In this study the use of
      a longitudinal design, with a pre-disaster baseline and a control group, suggests
      that these are robust findings.

PMID- 8306125
TI  - Jobst et al's "Detection in life of confirmed Alzheimer's disease using a simple
      measurement of medial temporal lobe atrophy by computed tomography".
AB  - "The medial temporal lobe of the brain is important for normal cognitive
      function, notably for memory, and is the region with the most extensive
      pathological change in Alzheimer's disease (AD). We wanted to find out if atrophy
      of the medial temporal lobe could be detected in life in patients in whom a
      diagnosis of AD was subsequently established histopathologically. The minimum
      width of the medial temporal lobe, measured by temporal-lobe-oriented computed
      tomography (CT) about one year before death, in 44 patients with a
      histopathological diagnosis of AD (cases) was nearly half (0.56 of the median)
      that in 75 controls of the same age with no clinical evidence of dementia (95%
      confidence interval 0.51-0.61). There was little overlap between the
      distributions of measurements in cases and controls. A cut-off (< 0.79 MoM)
      selected to yield a 5% false-positive rate gave an expected detection rate of
      92%. A cut-off selected to yield a false-positive rate of 1% (< 0.70 MoM) yielded
      a 79% detection rate. 20 of the 44 patients with histopathologically diagnosed AD
      had been scanned more than once before death, and the test (cut-off < 0.79 MoM)
      was positive in all 20 more than a year before and in 9/10 more than 2 years
      before death. In 10 subjects with dementia but with histopathology excluding AD,
      the mean minimum width of the medial temporal lobe was significantly greater than
      that in the cases with AD, but was not significantly different from that in
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306126
TI  - Poppy tea dependence.
AB  - A patient presenting with dependence on opium poppy tea infusion is reported.
      Poppy tea drinking, although previously described in certain parts of the UK,
      rarely presents in the form of a dependence syndrome. Issues relating to the
      management of poppy tea dependence are discussed, including the results of
      existing laboratory urinalysis for drugs of abuse, the calculation of opiate dose
      equivalence, and the likelihood of transition (or not) from use of poppy tea to
      use of other opiates.

PMID- 8306127
TI  - Treatment of cocaine abuse with monoamine oxidase inhibitors.
AB  - A cocaine-abusing patient was treated with phenelzine and tranylcypromine, under
      supervision, as deterrent drugs; other medical and psychological treatments had
      failed. When he eventually risked using cocaine there was no hypertensive
      reaction. Nevertheless, the deterrent effect seemed helpful in breaking his
      pattern of cocaine use, as confirmed by hair analysis for cocaine.

PMID- 8306128
TI  - Treatment of hysterical aphonia with hypnosis and prokaletic therapy.
AB  - A patient with chronic refractory hysterical aphonia was treated by prokalesis
      (challenge) and hypnosis within a psychotherapeutic relationship. A temporary
      remission was achieved but this was followed by subsequent relapse. This report
      illustrates the therapeutic effectiveness of prokaletic techniques. It also
      emphasises that these potent interventions are unlikely to achieve abiding change
      unless they are applied within the context of a longer-term relationship with a
      clinical team.

PMID- 8306129
TI  - Hyponatraemia and inappropriate secretion of antidiuretic hormone associated with
      the use of imipramine.

PMID- 8306130
TI  - Clozapine in the treatment of psychotic refractory depression.
AB  - A 40-year-old woman suffering from major depression with psychotic features was
      unresponsive to conventional therapy. After the administration of a wide range of
      drug treatments and ECT, she received clozapine. Depressive symptoms improved and
      psychotic features disappeared. It is suggested that clozapine could be efficient
      in psychotic refractory depression.

PMID- 8306131
TI  - Cyclic psychosis associated with the menstrual cycle.
AB  - Psychotic symptoms are not included under accepted definitions of premenstrual
      syndrome (PMS). We present a 14-year-old girl with PMS, who developed a late
      luteal cyclic psychosis during two consecutive premenstrual periods, which
      resolved completely after the onset of menses. She was treated with
      dehydroxyprogesterone for two cycles, and later with placebo for the next three
      consecutive cycles. Psychotic symptoms did not reappear following two psychotic
      cycles, and the PMS resolved within the next menstrual cycle. We suggest that
      cyclic psychoses associated with the menstrual cycle may be a specific benign
      entity, not included under the recognised functional psychoses. In some cases
      these psychoses could be classified as a subgroup of PMS.

PMID- 8306132
TI  - A case of delayed post-traumatic stress disorder with 'organic memories'
      accompanying therapy.
AB  - A case of post-traumatic stress disorder (PTSD) following a road traffic accident
      in which the onset of symptoms was delayed for 18 months until a widely reported
      major disaster occurred is described. A severe major depressive episode was
      precipitated, requiring treatment in its own right. During psychotherapy
      sessions, extreme emotions, heightened sensations, and 'organic memories'
      relating to the original accident were experienced.

PMID- 8306133
TI  - Automatism and post-traumatic stress disorder.
AB  - A soldier with post-traumatic stress disorder (PTSD) who committed a criminal act
      during a dissociative episode is described. This report and other published cases
      indicate that criminal acts can occur during dissociative episodes among people
      who suffer from PTSD. However, the evidence suggests that such incidents are rare
      and may be overemphasised. There often seems to be little relationship between
      the crimes committed by war veterans and their war experiences.

PMID- 8306134
TI  - Alcoholics with eating disorders.

PMID- 8306135
TI  - Anorexia nervosa: forced feeding and the law.

PMID- 8306136
TI  - The importance of severity as a factor in post-traumatic stress disorder.

PMID- 8306137
TI  - Right hemisphere damage v. dysfunction in Tourette's syndrome.

PMID- 8306138
TI  - Compulsive spitting as a neuropsychiatric symptom in Indian psychiatric practice.

PMID- 8306139
TI  - Psychiatric disorders in neurocysticercosis.

PMID- 8306140
TI  - Increased neuronal excitability in panic disorder.

PMID- 8306141
TI  - Moral reasoning and political conflict: the abortion controversy.
AB  - We argue that the abortion controversy has one major source--religion--and two
      less important ones--attitudes towards sexual permissiveness and women's
      employment. Traditional Christianity promotes opposition to abortion using three
      distinct modes of moral reasoning: through deductive moral reasoning, by the
      Christian world view's implication that abortion violates the sanctity of life
      and is a rebellion against God's design; through authoritative moral reasoning by
      appeal to Catholic dogma; and through consequentialist moral reasoning, as a
      means of control over sexuality and as a means of confining women's activities to
      the home. Even aside from Christian belief, adherence to traditional morality
      promotes opposition to abortion on these consequentialist grounds. We posit a
      model in which religious belief, anti-feminism, sexual permissiveness, and
      attitudes towards abortion are distinct concepts (a four-factor model) rather
      than all simply aspects of a single conservatism factor. We develop reliable,
      multiple item attitude scales; show that our four-factor model fits the data much
      better than the one-factor alternative; and test our hypotheses on new data from
      a large, representative national sample of Australia (N = 4540). Using maximum
      likelihood structural equation methods, we find that deductive reasoning from
      Christian belief is the most important source of opposition to abortion, with
      strong effects both direct and indirect. Exposure to the authority of the
      Catholic hierarchy is a real but weaker source of opposition. Consequentialist
      reasoning from traditional moral views on sex--partly buttressed by religion,
      partly independent of it--is also influential. But views on women's employment
      matter only a little, contrary to received wisdom.

PMID- 8306142
TI  - Constructive processes in person cognition.
AB  - The notion of constructive memory processes is imported from research on
      eyewitness memory to the area of social cognition. Mere questioning about the
      applicability of personality attributes to a target person is shown to affect
      subsequent memory-based judgements of that person. These constructive influences
      are to be distinguished, conceptually, from the global notion of priming effects.
      In Expt 1, the target person was first described as an extravert; afterwards,
      subjects had to indicate whether either desirable aspects of extraversion (self
      confidence) or undesirable aspects (exhibitionism) apply to the target or not.
      Mere questioning resulted in a congruent judgment bias towards the questioned
      attributes that did not generalize to a global halo effect. Experiment 2
      replicated the basic finding and demonstrated that this phenomenon is independent
      of a generation effect (i.e. the memory advantage of self-generated inferences).
      These results are interpreted in terms of (a) a reframing of the categorical
      distribution representing the information about the target person in memory and
      (b) a regressive tendency to assume intermediate default values rather than
      extreme values for questioned attributes under uncertainty. Alternative
      explanations in terms of demand effects or a conformation bias cannot provide
      sufficient accounts. The relevance of constructive processes to understanding
      self-fulfilling prophecies and other phenomena in social interaction is
      discussed.

PMID- 8306143
TI  - Comparison of nephrostomy drainage systems.
AB  - Forty patients undergoing nephrostomy insertion were randomised into 2 groups:
      those maintained on intermittently closed and those on permanently closed
      drainage systems. The average cost of managing a patient in the former group was
      one-eighth that of the latter and was not associated with any increase in
      morbidity.

PMID- 8306144
TI  - Long-term outcome in renal transplantation with terminal cutaneous ureterostomy.
AB  - We have reviewed the complications and follow-up in 6 patients who underwent
      kidney transplantation with cutaneous ureterostomy. Four patients had
      tuberculosis, 1 myelomeningocele and another congenital stenosis of the posterior
      urethra. Cutaneous ureterostomy was performed by suturing the edges of the distal
      end of the ureter to the skin. The mean follow-up was 40.6 months (range 2-105).
      The patient and graft survival rates were 83.3% and 66.6% respectively during the
      249 months of total follow-up. Significant bacteriuria and leukocyturia were
      constantly present and the incidence of urinary infection was 3.1
      episodes/patient/year. The early complications of the stoma were partial necrosis
      in 1 case and haematoma in another. The most frequent late complication was
      stomal stenosis requiring periodic dilatation. A plasma creatinine of 61.88 to
      114.92 mumol/l reflected good long-term graft function in the remaining patients.
      Terminal cutaneous ureterostomy is a simple technique with good long-term
      results.

PMID- 8306145
TI  - Humoral hypercalcaemia in renal carcinoma due to parathyroid hormone related
      protein.
AB  - Parathyroid hormone related protein (PTHRP) has been implicated in humoral
      hypercalcaemia of malignancy (HHM). We describe a patient with a renal carcinoma
      and hypercalcaemia, and for the first time have demonstrated a 4-fold PTHRP
      concentration gradient across a renal tumour bed. This provides further strong
      evidence that the primary tumour was the source of the PTHRP. The PTHRP 1-86
      content of the tumour tissue was 4.8 ng/g, similar to that previously found in
      tumours associated with HHM. In PTHRP-secreting tumours, PTHRP may be a useful
      oncological marker after surgical resection.

PMID- 8306146
TI  - Urinary solute transport by ileal segments. I. Effects of nicotinic acid.
AB  - This study was conducted to quantify urinary solute transport by the ileum, using
      an in vivo human model, and to determine the effect of nicotinic acid on this
      process. Patients were studied under both basal conditions and niacin therapy.
      The rates of solute transport were established by analysis of excretion indexes
      for each solute. Potassium and ammonium were absorbed by the ileum, while
      phosphorus, sodium and bicarbonate were secreted. The percentage excretion index
      of sodium and bicarbonate increased by approximately 100 and 600% respectively,
      causing a significant rise in urinary pH. Although not statistically significant,
      there was a tendency for chloride to be absorbed and for water to pass into the
      bowel lumen. Nicotinic acid 3 g/day had no significant effect on urinary solute
      transport.

PMID- 8306147
TI  - Changes in acid-base balance and calcium metabolism after urinary diversion
      through ileal segments. II. Treatment with nicotinic acid.
AB  - Investigations in animals have shown that nicotinic acid, an intestinal cyclic
      AMP inhibitor, partially corrects the metabolic changes associated with urinary
      diversion through intestinal segments. Blood and serum chemistry were studied in
      patients before and 3 to 5 months after undergoing urinary diversion through
      ileal segments, both with and without nicotinic acid treatment. It was found that
      diverted patients had metabolic acidosis, an increased anion gap and increased
      levels of serum alkaline phosphatase; there were no significant changes in serum
      PTH and vitamin D levels, calcaemia and phosphoraemia. There was a tendency
      towards dehydration, hypernatraemia, hyperchloraemia and secondary
      hyperaldosteronism produced by ileal secretion of a hypotonic fluid. Nicotinic
      acid 3 g/day significantly reduced the chloraemia but did not correct the
      metabolic acidosis, although it reduced its severity, since blood pH decreased
      when treatment was suspended. Nicotinic acid cannot be recommended for routine
      use in the management of metabolic acidosis after urinary diversion, and patients
      with a marginal renal reserve should not be considered for trans-intestinal
      urinary diversion.

PMID- 8306148
TI  - Effects of abdominal hysterectomy on urinary and sexual symptoms.
AB  - A prospective study of 102 women undergoing abdominal hysterectomy for benign
      conditions was performed in order to evaluate pre- and post-operative urinary and
      sexual symptoms. The mean age of the patients was 44.9 years (range 30-65).
      Urinary disorders such as urgency, dysuria, frequency, nocturia, slow bladder
      emptying, sensation of residual urine as well as stress and urge incontinence
      were observed pre-operatively and 2, 6 and 12 months post-operatively.
      Dyspareunia, libido and the number of orgasms were evaluated as disorders
      affecting sexual life. At follow-up 12 months post-operatively a statistically
      significant decrease in stress incontinence, frequency and nocturia was observed.
      Dyspareunia was also significantly less frequent and increased libido was
      experienced. It was concluded that abdominal hysterectomy does not provoke
      adverse urinary or sexual symptoms and that it can have beneficial effects.

PMID- 8306149
TI  - Characterisation of detrusor contractile function in relation to old age.
AB  - This report describes an age-related clinical study of detrusor muscle function
      using urodynamic data obtained from 1391 women and 324 men of different age
      groups who were free from overt neurological disease and diabetes. Isometric
      detrusor function during unstable activity was assessed by integrating the
      calculated force of unstable detrusor activity during filling of the bladder.
      Isotonic voiding activity was measured by calculating the velocity constant Q*,
      which reflects the speed of detrusor muscle shortening. In addition, the change
      in detrusor pressure on initiation of voiding and the post-micturition residual
      urine volume were recorded. Older patients of both sexes had higher residual
      urine volumes. Older women showed lower detrusor shortening velocities. There
      were no age-related differences in isometric detrusor function. Older women
      showed a tendency for the detrusor contraction to fail on initiation of voiding,
      whereas older men did not demonstrate this difference. Voiding dysfunction in
      late life was more marked amongst women and seemed to be related to a failure of
      isotonic detrusor function with no related changes in isometric function.

PMID- 8306150
TI  - Immunohistochemical detection of tissue-infiltrating lymphocytes in mild
      urothelial dysplasia.
AB  - The presence and distribution of immunocompetent cells in normal and dysplastic
      urothelium of the bladder were investigated in 3 patients. Using an indirect
      immunoperoxidase staining procedure, monoclonal antibodies reacting with B
      (Leu12+) and T (Leu4+) cells, cells of the suppressor/cytotoxic (Leu2a+),
      helper/inducer (Leu3a+) and natural killer (Leu7+) phenotypes, monocyte
      macrophages (LeuM3+), and cells expressing interleukin-2 receptor and HLA-DR
      antigen (HLA-DR+) were tested in all specimens. The results confirmed the
      presence of a well ordered and compartmentalised distribution of immunocompetent
      cells in the normal mucosa far from dysplasia. There was an increased number of
      lymphocytes in the hyperplastic/dysplastic urothelium with associated Von Brunn's
      nests. Leu2a+ cells, HLA-DR expressing cells and monocyte-macrophages were
      present inside the epithelium, particularly within dysplasia and von Brunn's
      nests, but the Leu3a+/Leu2a+ ratio was not inverted (0.48 + 0.1 to 0.74 + 0.2).
      These findings reveal that in mild urothelial dysplasia with von Brunn's nests
      there is a spatial modification of the immunological barrier associated with the
      mucosa.

PMID- 8306151
TI  - Cytogenetic analysis in transitional cell carcinoma of the bladder.
AB  - The potential use of numerical chromosomal abnormalities as predictive factors
      for the clinical behaviour of transitional cell carcinoma (TCC) was investigated.
      The effects on survival and progression-free survival were measured in 91
      patients with TCC treated by transurethral resection. The survival rate of
      patients having tumours with a diploid chromosomal modal number was significantly
      better than that of patients having tumours with a hyperdiploid chromosomal modal
      number. The survival rate of patients having TCC with diploid cells only was also
      significantly better than that of patients having TCC with both diploid and
      hyperdiploid cells. Progression-free survival was significantly higher in
      patients having TCC with a diploid modal number of chromosomes than in patients
      with a hyperdiploid modal number. Simultaneous evaluation of the modal chromosome
      number or chromosomal range, histological grade, category and mitotic index of
      the tumour, and the patient's age and sex as prognostic factors in multivariate
      analyses showed that the category of bladder carcinomas was the most important
      factor in predicting the survival rate. In patients with superficial tumours
      (category Ta and T1) the modal chromosome number was the most important factor in
      predicting survival. For progression-free survival, the modal chromosome number
      appeared to be the most important factor. It was concluded that the modal
      chromosome number in TCC was useful in predicting survival in patients with
      superficial tumours and in predicting progression-free survival in patients with
      tumours of all categories.

PMID- 8306152
TI  - Three-year follow-up of bladder tumours found on screening.
AB  - The clinical course, over a period of 3 years, of 17 bladder tumours found on
      screening a male population (2356 individuals) aged over 60, is reported. Even
      with this relatively small population, the importance of distinguishing
      pathologically between a pTa and a pT1 tumour is emphasised. The progression rate
      to date of pT1 tumours (1 of 9: 11%) is significantly less than that reported in
      larger studies on symptomatic patients. The simplicity of this screening process,
      together with the ease of out-patient investigation (combining ultrasound,
      flexible cystoscopy and urine cytology) indicate the need for a comprehensive
      prospective randomised trial to test the efficacy of screening for bladder
      tumours in populations who are known to be at risk.

PMID- 8306153
TI  - Bacillus Calmette-Guerin sensitises fresh transitional carcinoma cells and T24
      cell line to non-MHC-restricted cytotoxicity in vitro.
AB  - The activity of lymphokine (interleukin-2) activated killer (LAK) cells from 9
      patients with transitional cell carcinoma (TCC) was tested against autologous,
      freshly purified transitional carcinoma cells. Cytotoxicity was relatively low.
      Bacillus Calmette-Guerin (BCG) substantially augmented both LAK activity and the
      cytolytic activity of non-stimulated peripheral blood mononuclear cells (PBMC)
      against autologous TCC when tested with 6 additional TCC patients. A similar
      enhancing effect of BCG was noted with leucocytes obtained from normal donors
      when tested against an allogenic T24 cell line. Both natural killer (NK) cells
      and T cells appeared to be responsible for the increased cytolytic activity
      caused by BCG. No cytolytic activity was noted against normal transitional
      epithelial cells. Sensitisation of TCC cells to the immune system may explain the
      clinical effects of BCG.

PMID- 8306154
TI  - Urethral recurrences following radical cystectomy for invasive transitional cell
      carcinoma of the bladder.
AB  - A total of 177 patients with invasive transitional cell carcinoma of the bladder
      underwent radical cystoprostatectomy, of whom 13 underwent simultaneous
      urethrectomy. The remaining 164 patients were followed up regularly with
      urethroscopy and urethral cytology. Fifteen patients developed urethral
      recurrences, 4 of which were associated with relapses at other sites (recurrence
      rate 9%), with a mean recurrence-free interval of 13.5 months. Nine of the 11
      patients with isolated urethral recurrences underwent total urethrectomy and all
      except 1 are alive and disease-free 2 to 8 years later. One patient was salvaged
      by radiation therapy and refused further treatment. The 4 patients with other
      associated relapses died within 18 months. The urethral recurrence rate was
      correlated to different risk groups defined on the basis of tumour
      characteristics in the cystectomy specimen. This revealed a 70% urethral
      recurrence rate in the high risk group, 9.6% in the moderate risk group and 1.2%
      in the low risk group. However, no conclusion could be drawn regarding the
      influence of prostatic involvement on the urethral recurrence rate.

PMID- 8306155
TI  - Urological aspects of hemicorporectomy.
AB  - The indications for hemicorporectomy are few. However, with improvements in
      surgical techniques, anaesthesia and post-operative surgical care,
      hemicorporectomy may again become a reasonable treatment for certain patients
      with malignancies of the pelvis. A 2-stage procedure is described which consists
      of an initial staging celiotomy with urinary and faecal diversions. A non
      refluxing colon conduit is the preferred form of urinary diversion. The
      hemicorporectomy is performed approximately 2 weeks later. No complications were
      encountered in the post-operative period. Our experience and a review of the
      literature suggest that hemicorporectomy is a reasonable salvage procedure for
      certain patients with pelvic malignancies.

PMID- 8306156
TI  - Ureaplasma urealyticum in the urogenital tract of patients with chronic
      prostatitis or related symptomatology.
AB  - To elucidate the role of Ureaplasma urealyticum as a causative organism in
      chronic prostatitis we investigated its incidence in the urogenital tract in 131
      chronic prostatitis patients and 120 prostatodynia patients; the presence of
      common bacteria or Chlamydia trachomatis was also recorded. According to the 4
      glass localisation test, U. urealyticum (> or = 10(3) ccu/ml) was isolated from
      the prostates of 16 prostatitis patients and 2 prostatodynia patients; 5 of these
      prostatitis patients (but neither of the prostatodynia patients) had other
      bacteria in specimens after prostatic massage. Thus U. urealyticum was the sole
      organism isolated from the prostates of 11 prostatitis and 2 prostatodynia
      patients, which suggests that it is an aetiological agent in some cases of
      chronic non-bacterial prostatitis.

PMID- 8306157
TI  - Urethral stricture following transurethral resection of the prostate. The role of
      local anaesthetics.
AB  - In a multicentre prospective study, 261 patients undergoing transurethral
      resection of the prostate (TURP) in 17 urology departments were randomised to
      receive lubricating jelly containing either 3% tetracaine hydrochloride, 1%
      lignocaine hydrochloride, or no local anaesthetic. No patient had a history of
      urethral instrumentation or a previous urethral stricture. After 6 months' follow
      up, 25/79 patients (32%) treated with 3% tetracaine jelly developed urethral
      strictures, as did 4/92 patients (4%) who received 1% lignocaine and 2/90 (2%)
      who received the jelly without anaesthetic. It was concluded that the use of 3%
      tetracaine jelly is associated with a high incidence of post-TURP urethral
      strictures.

PMID- 8306158
TI  - Patterns of bone metastasis and their prognostic significance in patients with
      carcinoma of the prostate.
AB  - The different patterns of bone metastasis, metastatic load and their prognostic
      significance were examined in a consecutive series of 169 men with prostatic
      cancer and bone metastasis at presentation. Patients with an isolated metastasis
      in the pelvis or dorsal vertebrae had a better prognosis than those whose
      metastases were either diffuse or involved more distal sites such as the skull or
      the sternum, although all of these patients were classified as having M1 disease.
      Bone metastasis involving an area equivalent to 1 vertebral body equalled a
      metastatic load of 2. Based on their total metastatic load, 3 prognostic groups
      were identified with significant differences in case-specific survival despite
      receiving the same hormonal treatment. When comparing the potential efficacy of
      various treatments one must stratify the metastatic load, which is a powerful
      prognostic indicator of the outcome in patients with metastatic carcinoma of the
      prostate.

PMID- 8306159
TI  - Benign urethral polyps.
AB  - Ten male patients presented between 1985 and 1991 with benign urethral polyps.
      This lesion is believed to represent a developmental error in the invagination
      process of the submucous glandular material of the inner zone of the prostate.
      The clinicopathological features of the condition are discussed and the
      literature is reviewed.

PMID- 8306160
TI  - Further study of Sushruta's lateral perineal approach for primary repair of the
      ruptured posterior urethra.
AB  - Using Sushruta's lateral perineal approach, 16 primary repairs for complete
      rupture of the posterior urethra were carried out between January 1987 and
      November 1991. This approach to the urethra is short, safe, simple and direct;
      operative and post-operative complications are minimal and the total recovery
      period is short.

PMID- 8306161
TI  - Morbidity following groin dissection for penile carcinoma.
AB  - From 1962 to 1990, 231 inguinal and 174 ilio-inguinal lymphadenectomies were
      performed on 234 patients with penile carcinoma. The morbidity of inguinal
      lymphadenectomy included wound infection in 18%, skin edge necrosis in 61%,
      seroma formation in 5% of dissections, and lymphoedema in 25% of limbs. The
      morbidity of ilio-inguinal lymphadenectomy included wound infection in 14%, skin
      edge necrosis in 64%, seroma formation in 9% of dissections, and lymphoedema in
      29% of limbs. Pre-operative radiation to the groin significantly increased the
      healing complications. The routine use of a myocutaneous flap for primary
      reconstruction of the groin following ilio-inguinal lymphadenectomy resulted in
      100% primary wound healing and significantly reduced the post-operative hospital
      stay to a mean of 10 days.

PMID- 8306162
TI  - Suppurative epididymo-orchitis in young "high risk" patients--a new problem?
AB  - During a 4-year period we have treated 3 young patients with severe epididymo
      orchitis which progressed to suppuration (despite treatment with a range of
      antibiotics) and necessitated orchiectomy. All gave a history of "high risk"
      activity (2 homosexual, 1 sexual partner of intravenous drug user). One patient
      was suffering from acquired immune deficiency syndrome and another presented
      during seroconversion to HIV-positive status. Cytomegalovirus was the infective
      organism in one patient, but the pathogenesis in the others remains obscure.
      Investigations for atypical pathogens should be performed when young patients
      present with refractory epididymo-orchitis. These patients should also be
      counselled with regard to HIV testing.

PMID- 8306163
TI  - Microsurgery in the treatment of chyluria and scrotal lymphangial fistula.
AB  - Thirty-nine cases of chyluria and scrotal lymphangial fistula treated by
      microsurgery between April 1980 and October 1989 are presented. Several different
      methods were used. In males a lymphatico-venous anastomosis of the spermatic cord
      was performed and in females the lower inguinal lymph nodes were anastomosed to
      the branches of the greater saphenous vein. In patients with scrotal lymphangial
      fistulae, bilateral lymphatico-venous anastomosis was carried out after excision
      of the fistula and scrotoplasty. Thirty-seven patients were followed up for 1 to
      9 years, 36 being cured by a single operation.

PMID- 8306164
TI  - Epidermoid cysts of the testis: organ-preserving surgery following diagnosis by
      ultrasonography.
AB  - Epidermoid cysts of the testes are rare, benign tumours that can be visualised by
      high frequency ultrasonographic transducers. Their echo patterns are
      characteristic but not pathognomonic, so that inguinal exposure of the testis is
      required to confirm the diagnosis. However, sonography facilitates the planning
      of surgery, since excision of the tumour can be performed in an organ-preserving
      manner. In 6 patients with epidermoid cysts treated in this way between 1986 and
      1989, no recurrence was seen during a mean follow-up period of 37 months.

PMID- 8306165
TI  - Development of hydronephrosis in spina bifida patients: predictive factors and
      management.
AB  - A retrospective review of 209 children with spina bifida was performed to
      determine predictive factors for the development of hydronephrotic changes and to
      assess the outcome of management. Renal sonography demonstrated hydronephrosis in
      100 cases (48%). Two risk factors were identified: level of spinal defect and age
      of the patient. Higher spinal levels carried the greatest risk of hydronephrosis.
      The high risk age periods were the first 4 months of life, affecting children
      with high lesions, and the teenage years, affecting those on clean intermittent
      catheterisation (CIC). Seventy-nine hydronephrotic patients underwent treatment,
      whereas for 21 there was improvement in the sonographic appearance without
      intervention. CIC with or without anticholinergic pharmacotherapy was the most
      common treatment (58%), but often a combination of modalities was required to
      achieve improvement. The final result of all treatments was deemed satisfactory
      in 82% of cases. Renal sonography was a useful screening tool to detect upper
      tract changes in spina bifida patients.

PMID- 8306166
TI  - Reimplantation of the ureter in a transtrigonal mucosal groove.
AB  - Reimplantation of the ureter into a groove of the bladder mucosa has been used to
      simplify the procedure of reimplantation and overcome problems in trabeculated
      bladders by obviating the creation of a submucosal tunnel. Further experience is
      presented regarding this procedure on 40 ureters of patients with unilateral or
      bilateral vesicoureteric reflux, ureteric orifice(s) stenosis, bladder
      diverticula and posterior urethral valves submitted to simultaneous resection.
      Intra-operative observations, post-operative cystography and long-term results
      led to the conclusion that the procedure is technically easy, facilitates
      reimplantation in trabeculated bladders, safeguards the valve mechanism by
      preventing vesicoureteric reflux and shortens hospitalisation time.

PMID- 8306167
TI  - Endoscopic treatment of vesicoureteric reflux with collagen. Five years'
      experience.
AB  - Submucosal injections of bovine collagen (Zyplast) were administered to 67
      children and 7 adults with 115 refluxing ureters. Reflux was grade I in 14
      ureters, grade II in 54, grade III in 38 and grade IV in 9. All patients had a
      history of recurrent urinary infection. One year after treatment 70 ureters
      showed no reflux, 20 were grade I and 25 showed a complete recurrence. The cure
      rate was 81% if grade I recurrence is included. In all, 68 ureters were followed
      up for 2 to 4 years. In 19 ureters a second injection was given, 47 showed no
      reflux, 19 had grade I reflux and 2 had a recurrence. In 5 ureters reflux grade I
      disappeared without a second injection. The cure rate was 97%. Renal scarring was
      seen in 4 kidneys. Collagen injections are an adequate method of treatment for
      reflux grades I-III.

PMID- 8306168
TI  - Treatment of vesicoureteric reflux in the neurogenic bladder.
AB  - A retrospective co-operative study was conducted among 6 Italian paediatric
      surgical departments to assess the results of different forms of treatment of
      vesicoureteric reflux in patients with neurogenic bladder. Between January 1980
      and December 1989 we studied 641 neurogenic bladders in children, mainly due to
      spina bifida; reflux was detected in 199 patients with 263 refluxing ureters.
      Details of treatment were available for only 170 patients and they were divided
      into 2 main groups: conservative medical treatment (n = 127) and primary surgical
      treatment (n = 43). Medical treatment consisted mainly of clean intermittent
      catheterisation and the administration of appropriate drugs. In the surgical
      group 36 reimplantations, 6 cystostomies and 1 STING were performed. Fifteen
      patients underwent surgery as a secondary procedure. The results showed that
      approximately 50% of patients with reflux were cured by clean intermittent
      catheterisation and drug therapy. Ureteric reimplantation can be safely performed
      in patients with neurogenic bladder provided that a normally compliant, non-hyper
      reflexic bladder can be achieved by means of drugs or by bladder augmentation
      with bowel.

PMID- 8306169
TI  - Improved Mathieu repair for coronal and distal shaft hypospadias with moderate
      chordee.
AB  - A modified Mathieu "flip-flap" technique is described for coronal and distal
      shaft hypospadias with moderate chordee. The first improvement is the creation of
      a well vascularised skin flap by leaving the dartos tunica attached to the
      mobilised skin, thus making it possible to bridge urethral defects up to 2.5 cm.
      The second improvement is the correction of congenital curvature by partial
      chordectomy and dorsal plication of the tunica albuginea without the need for
      circumcision. Preputial reconstruction is possible if required. Twenty patients
      underwent the procedure with a follow-up of at least 2.5 years; 96 patients had a
      shorter follow-up. Complications in the group of 20 patients consisted of 1
      fistula, 2 meatal stenoses and 1 glanular dehiscence due to severe wound
      infection. There were no late complications.

PMID- 8306170
TI  - Epithelioid sarcoma of penis simulating Peyronie's disease.

PMID- 8306171
TI  - Local recurrent tumour after penis-conserving therapy. A plea for long-term
      follow-up.

PMID- 8306172
TI  - Fatal anaerobic infection following transrectal biopsy of a rare prostatic
      tumour.

PMID- 8306173
TI  - Misdiagnosis of prostatic primary duct carcinoma.

PMID- 8306174
TI  - Mesenteric endometriosis causing ureteric obstruction above the pelvic brim.

PMID- 8306175
TI  - An unusual renal mass: ?Wegener's granulomatosis.

PMID- 8306176
TI  - Prostatic epithelial polyp of the urethra.

PMID- 8306177
TI  - Recurrent renal angiomyolipoma associated with renal carcinoma in a patient with
      tuberous sclerosis.

PMID- 8306178
TI  - Ascariasis and the urinary bladder.

PMID- 8306180
TI  - Glyceryl trinitrate and external urethral sphincter spasm.

PMID- 8306179
TI  - Displacement of incontinence device into the bladder.

PMID- 8306181
TI  - Watertight pyeloplasty: a novel approach.

PMID- 8306182
TI  - Laparoscopic nephroureterectomy.

PMID- 8306183
TI  - Localisation of radiolucent stones in the ureter--extra coil of double pigtail
      stent as a 'pointer'.

PMID- 8306184
TI  - Atraumatic cannulation of the vas for per-operative vasography.

PMID- 8306185
TI  - Intra-operative percutaneous caliceal irrigation--a technique for clearing
      caliceal residue during percutaneous surgery.

PMID- 8306186
TI  - Re: Effectiveness of hematuria clinics.

PMID- 8306187
TI  - Neuromuscular diversity in archosaur deep dorsal thigh muscles.
AB  - The living members of the clade Archosauria, crocodilians and birds, differ
      markedly in the morphology of their deep dorsal thigh muscles. To investigate
      whether this diversity is accompanied by differences in motor pattern and muscle
      function, the hindlimbs of representative archosaurs were studied by
      electromyography and cineradiography during terrestrial locomotion. In a
      crocodilian, Alligator, the iliofemoralis and pubo-ischio-femoralis internus part
      2 are both active during the swing phase of the stride cycle. This appears to be
      the primitive motor pattern for archosaurs. There are four avian homologues of
      these muscles in the helmeted guineafowl, Numida. These are primarily active in
      the propulsive phase (iliotrochantericus caudalis and iliotrochantericus medius),
      the swing phase (iliotrochantericus cranialis) and a speed-dependent combination
      of the propulsive and/or swing phases (iliofemoralis externus). Differences
      between Alligator and Numida in the number and attachment of deep dorsal muscles
      are associated with dissimilar motor patterns and functions. Evolutionary
      modifications of neuromuscular control must be recognized when evaluating avian
      locomotor history, but are rarely considered by paleontologists. Even within the
      deep dorsal thigh muscles of Numida, developmentally and anatomically similar
      muscles are active out-of-phase. Therefore, although the actions of two adjacent
      muscles appear equivalent, their functions may differ dramatically. The diversity
      of deep dorsal thigh muscles in modern birds may be a good model for studying the
      relationship between activity pattern and peripheral morphology.

PMID- 8306188
TI  - The visual response properties of neurons in the nucleus of the basal optic root
      of the northern saw-whet owl (Aegolius acadicus).
AB  - The nucleus of the basal optic root (nBOR) in birds is a component of the
      accessory optic system (AOS) which is involved in the analysis of visual
      flowfields normally resulting from self-motion. Using standard extracellular
      techniques, we recorded from 81 single-unit and multi-unit clusters in the nBOR
      of the northern saw-whet owl, Aegolius acadicus, an avian species that has a
      visual system with frontal emphasis. These cells responded best to large patterns
      of random dots moving either upward (52%), downward (31%) or nasal to temporal (N
      T; contralateral visual field; 15%). Only 2 units (2%) preferred temporal to
      nasal motion. 'Up' units were found in the dorsal portion of the nucleus whereas
      'Down' units were located more ventrally. The N-T units were found in both the
      lateral margin of the nucleus and ventral to the Down units in the lateral half
      of the nucleus. About half of the units tested (10/19) responded to stimulation
      of the ipsilateral as well as the contralateral eye. For all but one cell, the
      direction preference of both eyes was the same in visual space. When compared
      with previous studies of pigeons (Columba livia) and chickens (Gallus
      domesticus), these findings reveal that the nBOR in all three avian species have
      important similarities with respect to direction preference and functional
      compartmentalization. Furthermore, the high proportion of binocular neurons found
      in the nBOR of the saw-whet owl is similar to the condition generally reported in
      frontal eyed mammals and hence may reflect adaptation.

PMID- 8306189
TI  - Melatonin receptor distribution in the brain and retina of a lizard, Anolis
      carolinensis.
AB  - Melatonin binding sites were identified in the brain and retina of the lizard
      Anolis carolinensis using in vitro autoradiography. Radioactive labeling was
      observed in areas which receive primary, secondary, and tertiary visual input:
      the superficial layers of the optic tectum, lateral geniculate nucleus, nucleus
      rotundus, dorsal ventricular ridge, and striatum. Other areas that demonstrated
      binding included the left medial habenular nucleus, the interpeduncular nucleus,
      medial cortex, dorsal cortex, mammillary nucleus, and septum. In the retina,
      melatonin binding was localized in the inner plexiform layer. Radioactive
      melatonin binding to the optic tectum was reduced in the presence of a
      nonhydrolyzable cyclic GMP analog, indicating that the melatonin receptor in the
      brain of this lizard is associated with a G-protein. These results suggest that
      melatonin receptor binding sites are widely distributed in the forebrain and
      midbrain of the iguanid lizard, and are prominent in areas of the nervous system
      that are associated with visual processing. The highest degree of melatonin
      binding appeared in the left medial habenular nucleus, interpeduncular nucleus,
      and dorsal ventricular ridge. This suggests that these brain regions may be
      important targets for the actions of melatonin, such as its effects on circadian
      rhythmicity, thermoregulation and photoperiodic reproduction.

PMID- 8306190
TI  - Central topography of anterior lateral line nerve projections in the channel
      catfish, Ictalurus punctatus.
AB  - Electroreception evolved in the catfishes probably as a specialization of the
      mechanosensory lateral line system. Fibers of the anterior lateral line nerve in
      catfishes innervate electrosensory ampullary organs and mechanosensory neuromasts
      of the head lateral line system. The purpose of this study is to determine the
      projection patterns of the major principal branches of the ALLN and to
      investigate the topography within the various nuclei of the terminal fields of
      these different branches. Fibers of the superficial ophthalmic, buccal and
      hyomandibular branches of the anterior lateral line nerve terminate in a
      somatotopic fashion within medullary and cerebellar nuclei. These fibers project
      to, and terminate within, several discrete nuclei in the medulla and cerebellum,
      notably the electrosensory lateral line lobe, the medial and caudal
      octavolateralis nuclei, and portions of a nuclear complex in the cerebellum
      called the eminentia granularis. Furthermore, the dorsoventral somatotopy in the
      medullary electrosensory nucleus is a reversed or 'mirror' image of that in the
      mechanosensory nucleus. This reversed map is similar to that observed in other
      electrosensory systems and suggests that there may be a common mechanism for the
      copying and preservation of spatial information as new systems are evolved from
      primitive sensory pathways.

PMID- 8306191
TI  - Changes in retinal structure during development and settlement of the goatfish
      Upeneus tragula.
AB  - The retinal structure of the goatfish Upeneus tragula was examined at various
      stages of the fish's development from pre-settlement pelagic larvae to benthic
      juveniles. Histological investigation revealed a double layer of cone inner
      segments in the dorsal retina and high cone and bipolar cell densities in both
      dorsal and ventral retina prior to settlement. During settlement reorganisation
      of the dorsal retina was found to occur, with the two cone layers slotting
      together to form a single layer. In both the dorsal and ventral retina cone and
      bipolar cell densities were rapidly reduced. Visual acuity, as calculated from
      histological data on cone density and lens diameter, was found to increase
      rapidly prior to settlement to an asymptote of approximately 27 minutes of arc,
      which corresponded to settlement. The changes in the visual system are thought to
      be associated with changes in both habitat and feeding behaviour at settlement
      when the fish leave the surface waters and begin a benthic mode of life using
      sensory barbels to search for sediment dwelling prey.

PMID- 8306192
TI  - Lipid absorption: passing through the unstirred layers, brush-border membrane,
      and beyond.
AB  - Lipids are components of our diet and luminal secretions, with physicochemical
      characteristics that determine their digestion and absorption in the
      gastrointestinal tract. Lipids include triglycerides, phospholipids, and
      cholesterol. Dietary lipids contain approximately 97% triglycerides, with small
      amounts of phospholipids and cholesterol. These components are important in cell
      membrane composition, fluidity, peroxidation, prostaglandin and leukotriene
      synthesis, and cellular metabolic processes. Lipids are implicated in the
      mechanisms of brain development, inflammatory processes, atherosclerosis,
      carcinogenesis, aging, and cell renewal. Duodenal hydrolysis of dietary lipids
      and biliary phospholipids and cholesterol is carried out by pancreatic lipase,
      colipase, phospholipase A2, and cholesterol esterase. Bile acid solubilization
      results in mixed micelles and liposomes, in gel and liquid crystal phases. Lipid
      digestion products pass across the intestinal unstirred water layer. For long
      chain fatty acids and cholesterol, passage across the unstirred water layer is
      rate limiting, whereas passage of short- and medium-chain fatty acids is limited
      by the brush-border membrane. Within the unstirred water layer, an acidic
      microclimate aids micellar dissociation so that protonated, and to a lesser
      extent, nonprotonated monomers then pass across the intestinal brush-border
      membrane. Absorptive mechanisms have been studied extensively in relation to
      lipid composition, fatty acid chain length, degree of unsaturation, essential
      fatty acid content, phospholipid components, and cholesterol. Enterocytes may
      take up lipids from the intestinal lumen or from lipoproteins of the bloodstream,
      but these pools are likely to be functionally distinct. Recent advances are
      reviewed, including recent advances in the area of microclimates,
      compartmentation, lipid binding proteins, intracellular trafficking, intestinal
      lipoproteins, release of lipids across the basolateral membrane, and dietary
      effects.

PMID- 8306193
TI  - Receptors for bradykinin and related kinins: a critical analysis.
AB  - Kinins exert a variety of biological actions and have been implicated in the
      pathogenesis of inflammation, pain, asthma, and other diseases. Kinins act
      through specific receptors that are widespread and belong to two major
      categories, B1 and B2. B2 has been cloned and shown to be of the rhodopsin type,
      consisting of seven hydrophobic membrane domains connected by extracellular and
      intracellular loops. Recent pharmacological findings from various laboratories
      suggest the existence of new receptor types, which have been named B3, B4, and
      B5. These findings are analysed critically, especially with respect to the
      criteria that have been used for affirming the existence of new receptor
      entities. The analysis is restricted to data obtained in isolated organs, almost
      exclusively smooth muscle preparations. Criteria for receptor characterization
      and classification are the order of potency of agonists and the apparent
      affinities of antagonists. The analysis reveals that receptors for bradykinin and
      related kinins are of two types, B1 and B2. B1 mediates the rapid acute response
      (smooth muscle contraction or relaxation) as well as some effects occurring more
      slowly (e.g., collagen synthesis). B1 receptor functions have been shown to be
      modulated by interleukins. B2 receptors are responsible for most of the kinins'
      biological effects, including arterial vasodilatation, plasma extravasation,
      venoconstriction, activation of sensory fibers (e.g., fibers for pain), and
      stimulation of the release of prostaglandins, endothelium-dependent relaxing
      factor (from endothelia), noradrenaline (from nerve terminals and adrenals), and
      other endogenous agents. The pharmacological characteristics of the receptor
      sites (B2) mediating this array of biological effects show differences between
      species, and two B2 receptor subtypes are proposed, namely B2A (rabbit, dog, and
      possibly man) and B2B (guinea pig, hamster, rat). B2A and B2B receptor subtypes
      have been characterized by using fairly selective agonists and competitive
      antagonists (e.g., D-Arg[Hyp3, D-Phe7,Leu8]BK). Noncompetitive antagonists (non
      equilibrium), such as HOE 140, do not discriminate between B2A and B2B subtypes.
      Species differences cannot account for the multiplicity of receptors that have
      been proposed for rat vas deferens, pre- and post-junctional sites, and rat
      uterus, guinea pig ileum, and rat blood pressure. The existence of hypothetical
      new receptor sites was based on data obtained with partial agonists and have not
      been substantiated by data obtained with potent pure antagonists. The B3
      receptor, proposed to explain the unusual behaviour of the guinea pig tracheal
      response to kinins, has to be carefully reconsidered after the finding that HOE
      140 acts as a pure antagonist on this tissue and shows a fairly high affinity for
      the tracheal site.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8306194
TI  - Effect of insulin on the altered thyroid function and adrenergic responsiveness
      in the diabetic rat.
AB  - We have previously reported the tail skin temperature response to isoproterenol
      as being significantly attenuated in male rats 4 weeks after the induction of
      diabetes with streptozotocin. The current study evaluated the time course of this
      altered adrenergic responsiveness and the role of thyroid hormone and insulin
      treatment in the tail skin temperature response. In the first study, the tail
      skin temperature response to isoproterenol was monitored weekly, for 6 weeks. The
      tail skin temperature response was similar in control and diabetic animals after
      1 week of streptozotocin treatment. However, after 2, 4, 5, and 6 weeks of
      diabetes the tail skin temperature response was significantly reduced. Total T3,
      T4, and free T4 concentrations were also significantly reduced in these diabetic
      animals. In a second study, the effects of graded doses of insulin treatment on
      thyroid hormone levels was assessed. The reduced thyroid hormone concentrations
      observed in untreated streptozotocin-diabetic rats were restored towards control
      levels in animals receiving the lowest dose of insulin (1 U/day), whereas higher
      doses of insulin were required to more closely restore euglycemia and lower
      glycated hemoglobin. A subsequent study, utilizing a 1-U/day dose of insulin,
      resulted in a normalization of the tail skin temperature response to
      isoproterenol, during 8 weeks of treatment in the treated diabetic rat. In a
      final study utilizing the spontaneous BB diabetic rat maintained on daily insulin
      treatment, no differences in the tail skin temperature response or thyroid
      hormone levels were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306195
TI  - Shivering and nonshivering thermogenic responses of rats subjected to different
      patterns of heat acclimation.
AB  - Male Wistar rats were divided into five groups: a control group kept at an
      ambient temperature of 24 degrees C for 14 days, and four heat-acclimated groups
      (two groups subjected to a constant ambient temperature of 33 degrees C for 4
      days or 14 days (HC-14) immediately preceding the measurement; and another two
      groups subjected to an ambient temperature of 33 degrees C for about 5 h once a
      day for 4 days, or 14 days (HI-14) just prior to the measurement). After the
      completion of the schedule, the rats were placed in a temperature-controlled
      chamber. Hypothalamic (Thy) and interscapular brown adipose tissue (TBAT)
      temperatures, oxygen consumption (VO2), and shivering activity were measured
      during a gradual fall in temperature of a water jacket surrounding the chamber
      (TW) from 30 to 10 degrees C at a constant rate of 0.18 degree C/min. During the
      fall in TW, VO2 and TBAT increased significantly and shivering was induced
      without associate changes in Thy in all groups. TW at the onset of a rise in
      metabolic heat production (onset of cold-induced thermogenesis) coincided with
      that at the onset of a rise in TBAT (onset of BAT thermogenesis), but was
      significantly higher than that at the onset of shivering. In HC-14 and HI-14
      rats, TWS at the onset of cold-induced thermogenesis and BAT thermogenesis were
      significantly higher than those in control rats, whereas TWS at the onset of
      shivering were not different from those in control rats. The onset of cold
      induced thermogenesis did not change after the 4-day heat exposure.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8306196
TI  - Neural effects of parathyroid hormone: modulation of the calcium channel current
      and metabolism of monoamines in identified Helisoma snail neurons.
AB  - Neuronal effects of parathyroid hormone (PTH) have been reported in vertebrates.
      The effect of PTH on invertebrate central neurons within the buccal ganglion of
      Helisoma trivolvis snails was examined in the present study. By using a vibrating
      probe, PTH was found to induce a transient calcium-dependent inward current in
      intact buccal ganglia. Intracellular microelectrode recording revealed that PTH
      broadened the spontaneous action potential in buccal B5 neurons in situ. By using
      the whole-cell configuration of the patch-clamp technique, PTH was demonstrated
      to increase the N-like calcium channel currents in isolated B5 neurons in a
      concentration-dependent manner. This effect of PTH on the N-like calcium channel
      currents depended on the activation of a G protein insensitive to pertussis
      toxin, but was unlikely to be mediated by the cyclic AMP dependent protein
      kinase. Furthermore, the release of gamma-glutamyl conjugate of dopamine from
      buccal ganglia was selectively increased in the presence of PTH. These results
      represent the first demonstration that a vertebrate peptide hormone, PTH,
      selectively modulates the N-like voltage-dependent calcium channel currents in
      identified invertebrate neurons. Therefore, a novel role of PTH in the regulation
      of invertebrate central neural functions is indicated.

PMID- 8306197
TI  - Pulmonary mechanical and vascular responses after acute hyperbaric oxygen
      exposure.
AB  - Pulmonary mechanical and vascular responses were studied in Sprague-Dawley rats
      exposed to hyperbaric oxygen (HBO, 100% O2 at 2.8 atm (1 atm = 101.325 kPa) for 6
      h). Two groups of animals were examined after HBO exposure: group HBO comprised
      rats examined immediately after exposure and group R consisted of rats left
      recovering while breathing air for 24 h before being studied. Both groups were
      compared with control rats, group C, not exposed to HBO. Pulmonary mechanical
      responses were measured by quantitating static lung compliance (Cs), wet to dry
      weight ratio (W/D) of lung tissue, and surface tension (ST) of broncho-alveolar
      lavage as a measurement of lung surfactant. Cs and W/D did not change
      significantly after exposure to HBO. ST was slightly lower in group R compared
      with group C (18.46 +/- 1.46 vs. 22.47 +/- 0.91 dynes/cm (1 dyne = 10 microN); p
      < 0.05). The effects of HBO on the pulmonary vasculature were studied in an
      isolated perfused lung preparation. Pulmonary vascular responses to hypoxia were
      recorded repeatedly over a period of 1 h. The percent increase in pulmonary
      vascular resistance (PVR) with hypoxia was blunted in group HBO and returned to
      the normal level in group R (8.2 +/- 2.4% in group HBO vs. 44.2 +/- 7.2% in group
      C and 42.9 +/- 11.2% in group R; p < 0.001). In a subgroup of rats, to assess the
      vascular smooth muscle contractility, 0.1 mL of KCl (15 mmol/L) was added to the
      perfusate and the pulmonary vascular responses were also recorded.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8306198
TI  - Comparison of core threshold temperatures for forehead sweating based on
      esophageal and rectal temperatures.
AB  - A protocol incorporating successive hot and cold water immersions, causing
      respective warming and cooling of the body, has been used to determine the core
      threshold for sweating. Disparate results have been reported for the core
      threshold of sweating, and these have been attributed to the possible existence
      of core temperature gradients during such a protocol. Spatial and temporal core
      temperature (Tc, degree C) gradients during dynamic changes in body temperature
      may give rise to different values of core temperature thresholds for sweating,
      depending on the Tc measurement site. In addition, during such an immersion
      protocol skin temperature transients may influence expression of thresholds using
      esophageal temperature (Tes). With these considerations, the effects of Tc
      gradients and skin temperature on Tc thresholds for sweating were examined.
      Subjects (n = 22) were immersed to the neck in 40 degrees C water until Tes
      reached 38.5 degrees C (phase 1), followed immediately by cooling in 30.6 degrees
      C water until extinction of sweating was observed (phase 2). Cooling was
      continued in the latter bath after the sweating extinction until total immersed
      time reached 50 min or until shivering was initiated (phase 3). During the trials
      continuous assessment was made of rectal temperature (Tre) and Tes, mean
      unweighted skin temperature (Tsk, degree C), forehead sweating rate (Esw, g.m
      2.min-1), oxygen consumption (VO2, L.min-1), and surface heat flux (Q, W.m-2).
      With the current protocol it appeared inappropriate to determine the Tc
      thresholds for onset of sweating, as sweating was initiated prior to any
      significant displacement of Tc, but was most likely influenced by Tsk and its
      rate of change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306199
TI  - Neuronal activity changes of ventromedial hypothalamic neurons and associated
      temperature responses in rats following scrotal thermal stimulation.
AB  - Experiments were conducted to determine whether ventromedial hypothalamic (VMH)
      neurons were responsive to thermal warming or cooling of the scrotum.
      Extracellular neuronal activity of VMH neurons was monitored in anesthetized
      groups of normothermic (core temperature maintained at 37 degrees C) or
      hypothermic (core temperatures allowed to decrease, 33.3 +/- 1.1 degrees C) male,
      Sprague-Dawley rats along with colonic (Tc), interscapular brown adipose tissue
      (TIBAT), tail (Tt), and scrotal (Tsc) temperatures during 30-min periods of
      scrotal cooling (small ice peak) or scrotal warming (small sealed pack containing
      40 degrees C tap water). In the normothermic group (65 VMH neurons recorded in
      total), 20 VMH neurons (31%) were classified as warm-responsive neurons (WRNs)
      (i.e., increased firing rate with scrotal warming and (or) decreased firing rates
      with scrotal cooling); 7 VMH neurons (11%) were classified as cold-responsive
      neurons (CRNs) (i.e., increased firing rate with scrotal cooling and (or)
      decreased firing rate with scrotal warming); and 38 VMH neurons (58%) were
      thermal nonresponsive neurons (TNRNs). In the hypothermic group (total of 85 VMH
      neurons recorded), 14 neurons (16%) were WRNs, 15 neurons (18%) were CRNs, and 56
      neurons (66%) were TNRNs. Results indicated that VMH neurons can respond
      selectively to changes in scrotal temperature, as previously shown for preoptic
      anterior hypothalamic neurons. Scrotal cooling and warming caused marked changes
      in T(sc) values in both the hypothermic and normothermic rats, but significant
      increases in TIBAT values indicative of brown adipose tissue thermogenesis did
      not occur.

PMID- 8306200
TI  - Prior glucose deprivation increases the first phase of glucose-induced insulin
      response: possible involvement of endogenous ATP and (or) ADP.
AB  - A possible implication of endogenously released ATP and (or) ADP in insulin
      response to glucose stimulation was investigated in the isolated rat pancreas.
      The first phase of insulin response to the same glucose concentration (8.3 mM)
      was much higher in pancreas previously perfused in the absence of glucose than in
      pancreas previously perfused with 4.2 mM glucose. A P2 purinoceptor antagonist,
      2,2'-pyridylisatogen tosylate, strongly reduced the higher first phase resulting
      from glucose deprivation; similarly, it reduced exogenous ATP-potentiated insulin
      response to a glucose increase from 4.2 to 8.3 mM. In contrast, 2,2'
      pyridylisatogen tosylate did not modify the first phase of insulin response to
      8.3 or 12.5 mM glucose in pancreas previously perfused with 4.2 mM glucose. Our
      results suggest that endogenous ATP and (or) ADP released in pancreatic islets in
      the absence of glucose could activate P2 purinoceptors and increase the magnitude
      of the first phase of insulin response to a glucose stimulation.

PMID- 8306201
TI  - Na(+)-K+ ATPase concentration in different adult rat skeletal muscles is related
      to oxidative potential.
AB  - To investigate the relationship among fibre type, oxidative potential, and Na(+)
      K+ ATPase concentration in skeletal muscle, adult male Wistar rats weighing 259
      +/- 8 g (mean +/- SE) were sacrificed and the soleus (SOL), extensor digitorum
      longus (EDL), red vastus lateralis (RV), and white vastus lateralis (WV) removed.
      These muscles were chosen as being representative of the two major fibre type
      populations: slow twitch (SOL) and fast twitch (EDL, RV, WV) and exhibiting
      either a high (SOL, EDL, RV) or low (WV) oxidative potential. Na(+)-K+ ATPase
      concentration (pmol.g-1 wet weight), measured by the [3H]ouabain binding
      technique, differed (p < 0.01) only between the WV (238 +/- 7.9) and the SOL (359
      +/- 9.6), EDL (365 +/- 10), and RV (403 +/- 12). Similarly, muscle oxidative
      potential as measured by the maximal activity of citrate synthase was different
      (p < 0.01) only between the WV and the other three muscles. Citrate synthase
      activity (mumol.min-1.g-1 wet weight) was 4.0 +/- 0.7, 12.3 +/- 0.9, 9.1 +/- 0.7,
      and 11.3 +/- 1.0 in the WV, SOL, EDL, and RV, respectively. These results
      indicate that Na(+)-K+ ATPase concentration is not related to the speed of
      contraction but to the oxidative potential of the muscle. Since chronic activity
      is a primary determinant of oxidative potential, it would be expected that
      increases in Na(+)-K+ ATPase would accompany increases in muscle utilization.

PMID- 8306202
TI  - Discussion: are gap junctions necessary for cell to cell coupling of smooth
      muscle?: an update.

PMID- 8306203
TI  - Effect of temperature on glyceryl trinitrate induced relaxation of rabbit aorta.
AB  - It has previously been shown that the vasodilatory response to glyceryl
      trinitrate (GTN) was decreased during hypothermic cardiopulmonary bypass. The
      purpose of these experiments was to determine the effect of temperature on GTN
      induced relaxation and on GTN biotransformation in rabbit aorta. It was
      determined that the EC50 of GTN on rabbit aortic rings (RARs) was increased
      significantly from 1.8 x 10(-8) M at 37 degrees C to 3.4 x 10(-8) M at 27 degrees
      C (p < 0.05). The production of NO by rabbit aortic strips (RASs) was
      significantly less at 27 degrees C compared with 37 degrees C after 80 min, being
      9.62 x 10(-11) +/- 13.2 x 10(-11) mol NO/g wet wt. RASs compared with 5.71 x 10(
      10) +/- 9.43 x 10(-11) mol NO/g wet wt. RASs, respectively (p < 0.05), after 80
      min incubation. There was no difference in the amount of glyceryl-1,2-dinitrate
      (1,2-GDN) produced from GTN at the two temperatures. The ED20 for NO-induced
      relaxation of RARs increased from 3.46 x 10(-10) +/- 2.24 x 10(-10) mol at 37
      degrees C to 1.01 x 10(-9) +/- 4.51 x 10(-10) mol at 27 degrees C (p < 0.05).
      These data indicate that the biotransformation of GTN and the release of NO were
      impaired by hypothermia, and that this, as well as a decrease in the tissue
      response to NO at 27 degrees C, explains the decrease in GTN activity at reduced
      body temperatures.

PMID- 8306204
TI  - Chytridiomycetous gut fungi, oft overlooked contributors to herbivore digestion.

PMID- 8306205
TI  - Cell interactions of Listeria monocytogenes L forms and peritoneal exudative
      cells in rats.
AB  - Listeria monocytogenes 4b and its forms without cell walls (L forms of a
      protoplastic type) were used to study in vivo interactions with host cells.
      Samples of peritoneal lavage fluid were obtained from rats intraperitoneally
      inoculated at intervals between 1 and 15 days after challenge, for scanning
      electron microscopic, bacteriological, biochemical, and cytometrical
      investigations. Scanning electron microscopic examination revealed continuous
      adhesion of L forms on the macrophage surface up to 15 days after inoculation.
      The persistence of the L forms within the peritoneal cavity was also shown
      bacteriologically at all sample times, while the parental bacterial forms were
      isolated from the peritoneal cavity up to 7 days after challenge. The total count
      of peritoneal exudative cells determined by automated flow peroxidase cytometry
      peaked on the 15th day in animals infected with parental forms, while in animals
      infected with L forms the peak was lower and the macrophage population was
      predominant. The glycolytic and acid phosphatase activity of peritoneal exudative
      cells was two times higher in rats infected with L form as compared with rats
      infected with the L. monocytogenes parental forms on the 3rd day after challenge.
      An understanding of the nature of the interactions between L forms of L.
      monocytogenes and peritoneal exudative cells found in vivo could be used to
      establish the influence of L forms on host cellular defense mechanisms.

PMID- 8306206
TI  - Fate of the fish pathogen Aeromonas salmonicida in the peritoneal cavity of
      rainbow trout.
AB  - A model was developed to study the fate of the fish pathogen Aeromonas
      salmonicida in vivo, inside a specialized intraperitoneal chamber implanted in
      rainbow trout, Oncorhynchus mykiss. Although normally recalcitrant to lytic
      agents in vitro, owing to the presence of its regular surface array (S layer), A.
      salmonicida was rapidly killed in the peritoneal cavity by a host-derived,
      soluble lytic activity present in peritoneal fluid. Peritoneal fluid was also
      found to kill other bacteria and lyse various types of erythrocytes, but was
      particularly lytic to A. salmonicida. Intraperitoneal survival of injected (free)
      A. salmonicida cells was several orders of magnitude higher than survival of
      implanted (restrained) cells. Injected free cells could evade the lytic activity
      of peritoneal fluid because they readily spread, initiating lethal infections.
      One evasion strategy was envisioned to be the penetration of peritoneal and (or)
      tissue macrophages. In spite of the killing mechanisms of these phagocytic cells,
      A. salmonicida was still able to survive and even replicate inside head kidney
      macrophages, thereby supporting the notion of A. salmonicida as a facultatively
      intracellular pathogen. Intraperitoneal chambers in rainbow trout may constitute
      a valuable experimental tool for studying the in vivo fate of A. salmonicida, and
      perhaps of other fish pathogens as well.

PMID- 8306207
TI  - Use of the cytomegalovirus antigenemia (CMV-Ag) assay for the detection of CMV in
      the blood of AIDS patients.
AB  - Direct specimen testing was performed on 186 peripheral blood specimens to
      identify the presence of antigen to cytomegalovirus (viz., the cytomegalovirus
      antigenemia (CMV-Ag) assay). Confirmatory testing was performed using the shell
      vial indirect immunofluorescence assay (SVA-IFA), the indirect immunoperoxidase
      assay (TC-IPA), and conventional tube culture isolation (TC-CPE). The primary
      reagent for the CMV-Ag assay consisted of anti-CMV monoclonal antibody directed
      against the internal matrix structural phosphoprotein (1C3; Clonatec-Biosoft,
      France). The 72-kDa early nuclear antigen (Dupont) was utilized in the SVA-IFA
      and the TC-IPA. All test systems received an equal number of polymorphonuclear
      leukocytes in the inoculum. CMV was detected and isolated from 30% (55/186) of
      the specimens evaluated by either one or a combination of the tests. Detection
      and (or) isolation of CMV from blood by the CMV-Ag assay, SV-IFA, TC-IPA, and TC
      CPE occurred at a rate of 17 (31/186), 12 (22/186), 16 (29/186), and 26%
      (49/186). Three of 55 positive specimens were identified only by the CMV-Ag
      assay; each patient in question, however, had at least one previous CMV isolate.
      No significant differences in sensitivity occurred between the CMV-Ag assay, the
      SVA-IFA, or the TC-IPA. However, TC-CPE including the blind passage of all
      negative tube cultures yielded a significantly larger number of positive blood
      specimens than either of the rapid detection methodologies. The CMV-Ag assay
      encompasses the benefits of a nonculture system, is simple to perform and easy to
      read, permits a same-day diagnosis, and requires less reagents than the routinely
      used SVA-IFA or TC-IPA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306208
TI  - Detection of Escherichia coli by the nutrient agar plus 4-methylumbelliferyl beta
      D-glucuronide (MUG) membrane filter method.
AB  - A two-step membrane filter procedure was evaluated to determine the ability to
      differentiate Escherichia coli from other coliform bacteria recovered from water.
      M-Endo LES agar incubated at 35 degrees C for 24 +/- 2 h was used as the initial
      isolation medium. Membranes containing coliform colonies were transferred to
      nutrient agar plus 4-methylumbelliferyl beta-D-glucuronide (MUG) and incubated
      for an additional 4 h at 35 degrees C. Escherichia coli colonies were
      distinguished by fluorescence when viewed under a long-wavelength ultraviolet
      light. A total of 119 MUG-positive colonies were isolated from 15 water sources,
      of which 115 (96.6%) were identified as E. coli. An examination of 182 pure
      culture environmental E. coli isolates revealed that 167 isolates (91.8%)
      exhibited fluorescence on the nutrient agar plus MUG medium. Survivors of E. coli
      cultures exposed to chlorination were also capable of producing a positive MUG
      reaction.

PMID- 8306209
TI  - Pseudomonas aeruginosa UG2 rhamnolipid biosurfactants: structural
      characterization and their use in removing hydrophobic compounds from soil.
AB  - The structure of two rhamnolipid biosurfactants produced by Pseudomonas
      aeruginosa UG2 was studied. Analyses by gas chromatography-mass spectrometry and
      nuclear magnetic resonance spectroscopy showed these two rhamnolipids to be alpha
      L-rhamnopyranosyl-beta-hydroxydecanyol-beta-hydroxydecanoate and 2-O-alpha-L
      rhamnopyranosyl-alpha-L-rhamnopyranosyl-beta-hydroxydecan oyl-beta-
      hydroxydecanoate. The ability of UG2 rhamnolipid biosurfactants to enhance
      removal of naphthalene, anthracene, phenanthrene, fluorene, 2,2',5,5'
      tetrachlorobiphenyl, and 3,3',4,4',5,5'-hexachlorobiphenyl into the aqueous phase
      was affected by soil type, hydrocarbon equilibration time, and biosurfactant
      adsorption to soil. Partially purified UG2 biosurfactants at a concentration of 5
      g/L removed approximately 10% more hydrocarbon from a sandy loam soil than slit
      loam soil. High levels of UG2 rhamnolipids adsorbed to soil. In 18% (w/v) soil
      slurries 74, 49, 38, and 20% of 0.5, 1, 2, and 5 g UG2 rhamnolipids/L,
      respectively, were bound to the soil phase. Sodium dodecyl sulphate recovered
      lower levels and Witconol SN70 higher levels of phenanthrene and 2,2',5,5'
      tetrachlorobiphenyl than UG2 biosurfactants.

PMID- 8306210
TI  - Reconstitution of glucose uptake and chemotaxis in Pseudomonas aeruginosa glucose
      transport defective mutants.
AB  - Wild-type glucose uptake and glucose chemotaxis activities were restored in
      glucose transport defective Pseudomonas aeruginosa strains PFB360 and PFB362
      after introduction of plasmid pPZ129, containing a 1.1-kilobase DNA fragment that
      is essential for the expression of the P. aeruginosa periplasmic glucose binding
      protein. The restoration of glucose uptake and chemotaxis to wild-type levels in
      these strains was also achieved by reconstitution with cold-shock fluid and
      purified glucose binding protein isolated from P. aeruginosa PA01 wild-type
      strain H103 grown in conditions resulting in the induction of the high-affinity
      glucose transport system. Glucose uptake was determined by whole cell uptake and
      shock fluid binding of D-[U-14C]glucose, using standard filter binding assays.
      Positive chemotaxis towards glucose was assessed by capillary assays using 10 mM
      glucose, the amount required for optimal chemotaxis, and judged by plating
      capillary contents accumulated after 30 min.

PMID- 8306212
TI  - Interpretation of breast biopsies.

PMID- 8306211
TI  - The National Breast Screening Study: a postscript or back to basics.

PMID- 8306213
TI  - The Angelchik antireflux prosthesis: long-term clinical and technical follow-up.
AB  - OBJECTIVE: To evaluate the long-term clinical outcome and compare the rupture
      rate of the two generations of the silicone Angelchik antireflux prosthesis.
      DESIGN: A cohort study. Follow-up ranged from 61 to 119 months. SETTING: A
      university teaching hospital. PATIENTS: Sixty-three patients: 33 patients
      received the first generation Angelchik device (group 1) and 30 patients received
      a second generation design (group 2). The two groups were comparable for sex
      ratio, mean age and duration of symptoms. INTERVENTIONS: Implantation of the
      Angelchik prosthesis. MAIN OUTCOME MEASURES: Comparison of the rupture rate and
      migration of the prosthesis as assessed by patient questionnaire, telephone
      interview and radiography of the abdomen. RESULTS: The prosthesis remained in a
      good position in 53% of group 1 patients and 93% of group 2 patients. The
      prosthesis was removed in 40% of group 1 patients, most often for rupture, and in
      only 7% of patients in group 2, to relieve dysphagia (p < 0.01). Grading on a
      Visick scale demonstrated a good result in 37% of group 1 patients and 69% of
      group 2 patients. Long-term dysphagia was the most prevalent adverse effect, seen
      in 45% of patients whose prosthesis was in a good position, and symptomatic
      reflux recurred in 8%. CONCLUSIONS: The second generation of the Angelchik
      prosthesis, resulted in a reduced rupture rate of the prosthesis. Nevertheless
      the high complication and the failure rates militate against continued
      implantation of the prosthesis.

PMID- 8306214
TI  - Cystic hydatid lung disease in northwest Canada.
AB  - OBJECTIVE: To determine the optimal treatment of sylvatic cystic hydatid lung
      disease. DESIGN: Retrospective case study. SETTING: Five Edmonton hospitals
      serving northern Alberta and parts of the Northwest Territories. PATIENTS:
      Fourteen patients with cystic (Echinococcus granulosus) hydatid lung disease.
      INTERVENTIONS: Cyst enucleation, wedge resection and pulmonary lobectomy. MAIN
      OUTCOME MEASURES: Eradication of pulmonary hydatid disease and complications of
      treatment. RESULTS: Mean patient age was 32 years. Eight patients were
      symptomatic. Liver cysts were present in three patients. One of the three
      patients managed by observation required surgery for an expanding cyst. Surgery
      (13 procedures in 12 patients) was successful in eradicating pulmonary hydatid
      disease: 8 cyst enucleations, 3 wedge resections and 2 lobectomies were done.
      There was only one major postoperative complication (pneumatocele requiring
      repeat surgery). Intraoperative cyst rupture occurred in five cases, but
      anaphylaxis or seeding did not result. There were no bronchopleural fistulae.
      CONCLUSIONS: Sylvatic cystic hydatid lung disease is more benign than pastoral
      hydatid disease. Patients with asymptomatic cysts should be managed by
      observation. Surgery, consisting of endocyst enucleation or wedge resection, is
      indicated for symptomatic, enlarging or infected cysts.

PMID- 8306215
TI  - Chronic, contained rupture of aortic aneurysms associated with vertebral erosion.
AB  - Chronic, contained rupture of aortic aneurysms is an important subset of ruptured
      aneurysms. Their presentation is unusual, and the diagnosis may be delayed. The
      associated vertebral erosion may contribute to the difficulty in diagnosis. The
      courses of three patients with chronic, contained rupture of an aortic aneurysm
      associated with vertebral erosion are presented. In each case the presentation
      was unusual and the initial diagnosis delayed. Computed tomography demonstrated
      the contained rupture and vertebral erosion in all cases. Microorganisms were
      cultured from all three aneurysms. Repair was successful in all cases. Contained
      rupture of an aortic aneurysm should be considered in older patients with
      unexplained back pain, and the possibility of this condition should not be
      ignored when there is a history of arthritic back pain or a radiograph suggestive
      of degenerative disease. Urgent surgical repair is indicated to prevent lethal,
      uncontrolled hemorrhage.

PMID- 8306216
TI  - Definition and management of abdominal aortic aneurysms: results from a Canadian
      survey.
AB  - OBJECTIVE: To assess how vascular surgeons define and manage asymptomatic
      abdominal aortic aneurysms (AAAs) 5.4 cm in diameter or smaller. DESIGN:
      Descriptive survey. SETTING: All provinces and territories of Canada.
      PARTICIPANTS: One hundred and ninety-one vascular surgeons. INTERVENTIONS: A 12
      item questionnaire sent in two mailings to all vascular surgeons who were members
      of the Canadian Society for Vascular Surgery. MAIN OUTCOME MEASURES: Definition
      and routine management of asymptomatic AAAs assessment of aneurysm size before
      elective surgery and basic personal data. RESULTS: One hundred and sixty-seven
      (87%) vascular surgeons responded to the mailings; 149 (78%) completed the
      questionnaire. The majority of respondents were experienced (78%), academic (70%)
      vascular surgeons. AAAs were defined in any one of four ways. There was notable
      consistency regarding the size range in which vascular surgeons seriously
      considered elective surgical repair of small aneurysms. CONCLUSION: Standards
      need to be developed to define what constitutes a small AAA if meaningful
      research on small aneurysms is to be conducted.

PMID- 8306217
TI  - Use of desmopressin acetate to reduce blood transfusion requirements during
      cardiac surgery in patients with acetylsalicylic-acid-induced platelet
      dysfunction.
AB  - OBJECTIVE: To determine whether desmopressin acetate (DDAVP) has the ability to
      reduce blood loss in patients with a known bleeding tendency. DESIGN: A
      randomized, double-blind, placebo controlled study. SETTING: A university
      teaching hospital. PATIENTS: Men under the age of 70 years who had taken
      acetylsalicylic acid within 7 days of scheduled coronary artery bypass surgery.
      Patients with an abnormal hematologic profile or a history of bleeding or who
      were receiving heparin or undergoing repeat coronary bypass surgery were
      excluded. Forty-four patients were randomized with restriction in blocks of 10;
      20 received DDAVP and 24 received a placebo. MAIN OUTCOME MEASURES: Blood loss
      and blood transfusion requirements. RESULTS: Patients treated with DDAVP lost
      significantly (p < 0.01) less blood than those receiving a placebo (1543 mL
      versus 2376 mL respectively). Nineteen patients had a blood loss of more than
      2000 mL; 15 of these were in the placebo group. Significantly (p < 0.02) fewer
      patients receiving DDAVP required blood transfusion (9 versus 18). CONCLUSIONS:
      DDAVP reduces blood loss during cardiac bypass surgery in patients who have taken
      acetylsalicylic acid within 7 days before operation.

PMID- 8306218
TI  - Heparinized saline versus normal saline in maintaining patency of the radial
      artery catheter.
AB  - OBJECTIVE: To compare the ability of normal versus heparinized saline infusion to
      maintain patency of the radial artery catheter used for monitoring or multiple
      blood sampling. DESIGN: Randomized double-blind trial. SETTING: A university
      affiliated hospital. PATIENTS: All 108 patients admitted to the surgical
      intensive care unit who required radial arterial line catheters. Excluded were
      patients who required emergency admission, those who refused to give consent,
      those who needed anticoagulants, thrombolytic or platelet therapy, those whose
      cannulation site was other than the radial artery, inadvertent discontinuation of
      the arterial line or incomplete data collection. This resulted in a sample of 78
      adults, randomized according to date of admission. INTERVENTIONS: Forty patients
      admitted on odd-numbered dates received heparinized normal saline (2 units/mL),
      and 38 patients admitted on even dates received normal saline, both as continuous
      flush solutions. MAIN OUTCOME MEASURES: Measurement of radial artery flow and
      pressure before and after cannulation, and catheter patency during cannulation.
      RESULTS: The type of flush solution did not adversely affect the radial artery or
      the hand in any measurable way. Catheter blockage occurred in three patients
      receiving heparinized saline and seven patients receiving normal saline as the
      flush solution (p = 0.06). At 96 hours of cannulation, 92% of the catheters in
      the heparinized saline group were patent compared with 74% in the normal saline
      group. Intra-arterial blood pressure was inaccurate compared with the brachial
      cuff pressure in 6 patients in the heparinized saline group compared with 14
      patients in the normal saline group (p < 0.03). CONCLUSIONS: There is no
      significant difference between flushing with normal saline and heparinized saline
      in the maintenance of radial arterial line patency. However, the use of a
      continuous heparinized flush solution in pressurized arterial lines is beneficial
      in that it results in greater accuracy of blood pressure monitoring than normal
      saline infusion.

PMID- 8306219
TI  - Malignant lymphoma of bone.
AB  - OBJECTIVE: To evaluate the diagnosis and management of patients with malignant
      lymphoma of bone. DESIGN: A case series review in which the minimum follow-up was
      24 months and the mean follow-up was 49 months. SETTING: All patients were
      managed at a tertiary care centre, although initial biopsies were often done in
      community centres. PATIENTS: Selected for review were 15 of 18 consecutive
      patients who were referred to the Musculoskeletal Oncology Unit at the Mount
      Sinai Hospital, Toronto, between 1984 and 1989, with a bone lesion as the
      presenting symptom of lymphoma. The three excluded patients included two with
      diffuse nodal disease at presentation and one who had a second, unrelated
      malignant tumour. INTERVENTIONS: Staging studies (hematologic investigations,
      radiography, technetium bone scanning and computed tomography), surgical biopsies
      of the lesion, chemotherapy, radiotherapy and in some cases surgical resection of
      the lesion. MAIN OUTCOME MEASURES: The number of biopsies required for diagnosis
      and the incidence of complications that required operative intervention. RESULTS:
      Seven of the 15 patients required more than one biopsy to establish the
      diagnosis. Five patients required surgical procedures for late complications that
      included pathologic fractures, wound infection and osteonecrosis. At 24 months'
      follow-up, 13 patients were disease free and 2 had died. CONCLUSIONS: Proper
      biopsy and pathological evaluation are crucial in the diagnosis of lymphoma of
      bone. These measures will decrease the necessity for repeat biopsies. Lymphoma is
      best managed medically. Surgery should be reserved for biopsy and for treatment
      of the complications of therapy.

PMID- 8306220
TI  - Craniocervical fusion with contoured Luque rod and autogeneic bone graft.
AB  - OBJECTIVE: To examine the efficacy of internal craniocervical fixation with a
      Luque rod and autogeneic bone graft for craniocervical instability. DESIGN: A
      case series. SETTING: A university-affiliated hospital. PATIENTS: Six patients
      with craniocervical instability from diverse causes. INTERVENTIONS:
      Craniocervical fusion with a custom-formed Luque rod wired to the occiput and a
      variable number of vertebrae overlaid with autogeneic bone graft, followed by
      bracing with either a halo vest or a removable, stiff, plastic cervical orthosis.
      MAIN OUTCOME MEASURES: Craniocervical fusion and neurologic stability. RESULTS:
      All patients maintained good craniocervical alignment. Radiologic bony fusion was
      achieved in five patients. Three patients remained neurologically stable and
      three had improved neurologic status. CONCLUSION: Craniocervical fusion with the
      contoured Luque rod and autogeneic bone grafting, usually in combination with a
      temporary plastic cervical orthosis, is of value in managing craniocervical
      instability.

PMID- 8306221
TI  - Disseminated intravascular coagulation complicating gastric perforation in a
      bulimic woman.
AB  - The authors report the case of a 43-year-old woman who presented with an acute
      abdomen and in shock after a bulimic episode. The fatal outcome in this case was
      due to disseminated intravascular coagulation (DIC). The death represents the
      fifth reported in the literature among bulimic or anorexic patients who sustained
      a gastric perforation. This is the first documented case of DIC in a bulimic
      patient who died. The other reported cases are reviewed, and the findings are
      compared with those in this case.

PMID- 8306222
TI  - Use of a pericardial xenograft patch in repair of resected retrohepatic vena
      cava.
AB  - Complete surgical excision of malignant tissue is mandatory for the long-term
      survival of patients with hepatic metastases from colorectal carcinoma.
      Involvement of the inferior vena cava (IVC) may prevent this resection. The
      authors describe the case of a 64-year-old man who underwent right hepatic
      lobectomy for metastases from colorectal carcinoma. Partial involvement of the
      IVC by tumour necessitated resection of a large portion of its wall. Venous
      continuity was re-established with a large bovine pericardial patch. At follow-up
      2 years after the repair, the IVC was still patent and the vessel diameter was
      normal. On enhanced computed tomography, the patch was indistinguishable from the
      native vessel.

PMID- 8306223
TI  - Pseudoaneurysm of the cystic artery: a rare cause of hemobilia.
AB  - Aneurysms are a rare cause of hemobilia. The arteries most frequently involved
      are branches of the hepatic or gastroduodenal arteries. The authors report the
      case of a patient with hemobilia secondary to a pseudoaneurysm of the cystic
      artery. Only six other cases have been reported in the literature, and in all of
      them the condition was associated with inflammation of the gallbladder. Selective
      hepatic arteriography is the procedure of choice for diagnosis. Colour-Doppler
      ultrasonography aided in the diagnosis in the patient described in this report
      and may prove to be useful in equivocal cases. Cholecystectomy and ligation of
      the cystic artery with proximal control of the hepatic artery should be performed
      as soon as the diagnosis is made.

PMID- 8306224
TI  - A variant of Poland's syndrome.
AB  - A case of Poland's syndrome--the association of congenital thoracic abnormalities
      with ipsilateral syndactyly--in a newborn infant is described. The infant
      demonstrated unusual manifestations of the syndrome: there was extension of the
      liver through the chest, and there was absence of a whole arm rather than
      hypoplasia and syndactyly. The authors describe the investigation and treatment
      of this infant, and they discuss the diversity of findings in Poland's syndrome.

PMID- 8306225
TI  - Defining abdominal aortic aneurysms.

PMID- 8306226
TI  - Sudden rupture of an indirect inguinal hernial sac with extravasation in two
      patients on continuous ambulatory peritoneal dialysis.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) is commonly used to treat
      patients suffering from end-stage renal failure. This method can be used on a
      long-term basis and in the short term for patients awaiting renal
      transplantation. Inguinal hernias are a potential source of morbidity for these
      patients. Therefore, when patients with inguinal hernias require long-term
      peritoneal dialysis, the hernia should be repaired if the patient's medical
      status will allow it. The authors report on two patients maintained on CAPD who
      experienced rapid enlargement and perforation of a previously undiagnosed
      asymptomatic inguinal hernia. The hernia was repaired successfully, without
      complication, in both cases.

PMID- 8306227
TI  - The surgeon's ego: moulding the demon to the needs of the '90s.

PMID- 8306228
TI  - Humanism and psychiatry.

PMID- 8306229
TI  - Complex visual hallucinations in macular degeneration.
AB  - A previously healthy elderly patient with a recent onset of macular degeneration
      presented for evaluation of elaborate complex visual hallucinations. The
      patient's psychiatric evaluation and level of cognitive functioning were normal.
      A diagnosis of organic hallucinosis secondary to macular degeneration was made,
      and the hallucinations ceased with increased sensory stimulation in the hospital.
      Numerous diagnoses were considered and are discussed, including Charles Bonnet
      hallucinations and peduncular hallucinosis.

PMID- 8306230
TI  - Obtaining a family psychiatric history: is it worth the effort?
AB  - The purpose of this study was to determine whether, for first-degree relatives of
      patients presenting to a mood disorders clinic, family history information on
      psychiatric conditions collected by a psychiatrist and incorporated into the
      patient's medical records is as informative as that gathered during an interview
      specifically designed to collect family history data. The study group consisted
      of 472 first-degree relatives of 78 randomly selected index cases from a large
      mood disorders genetic database. Family history of psychiatric disorders recorded
      in regular psychiatric medical records ("clinician history"), and data obtained
      by a genetic counsellor administering specific family psychiatric history
      questionnaires to patients and multiple family informants ("family history") were
      compared using a kappa statistic. Good agreement between the two methods on the
      presence or absence of a psychiatric disorder was found among first-degree
      relatives of index cases, but poor agreement was found with respect to the
      presence or absence of a specific mood disorder diagnosis(es) in a relative. The
      results suggest that a clinician-generated family psychiatric history is
      sensitive to the presence or absence of a psychiatric disorder when compared to a
      more structured detailed genetic interview. However, for research purposes, a
      clinician-generated family psychiatric history of a specific mood disorder
      diagnosis, without supporting collateral information, may not be reliable for use
      in supporting a mood disorder diagnosis in a patient and/or his relatives.

PMID- 8306231
TI  - Determination of financial competence in consultation-liaison psychiatry.
AB  - The aging of our population will require physicians to become more aware of the
      issues surrounding the determination of financial competence. This retrospective
      study involved the review of 46 medical or surgical patients in a university
      teaching hospital that were referred to the psychiatric consultation-liaison team
      for assessment of financial competency. Charts were reviewed for completeness of
      documentation using suggested criteria for determination of financial competence.
      The study found that while many criteria were frequently documented,
      documentation was incomplete for important criteria, such as calculating
      abilities, judgement, the patient's appreciation of the consequences of financial
      competence, presence of delusions with regard to finances and the patient's
      awareness of debt. Concerns are expressed regarding a physician's ability to
      recall details pertaining to cases before a tribunal without complete and careful
      documentation. The importance of establishing formal criteria for the
      determination of financial competence is also discussed.

PMID- 8306232
TI  - Hyperthyroidism after treatment with lithium.
AB  - The association between treatment with lithium and hypothyroidism is well
      documented. Reports of hyperthyroidism are rare and it is less well known among
      patients treated with lithium. It may be overlooked simply because the clinician
      will be watching for hypothyroidism, the reverse phenomenon. This paper describes
      the cases of four patients who have been on long term lithium treatment, all of
      whom developed Graves' disease, or an atypical form of hyperthyroidism. Some
      suggestions are offered to account for the mechanism underlying this unusual
      association. Although hyperthyroidism may be rare among patients receiving
      lithium, astute clinical observation and appropriate laboratory tests are called
      for to detect the early stages of such thyroid dysfunction and to provide
      appropriate intervention.

PMID- 8306233
TI  - [Eating disorders in an adolescent population with insulin-dependent diabetes].
AB  - The existence of a relationship between Insulin-Dependent Diabetes and eating
      disorders has recently been observed, but its prevalence and impact on somatic
      functioning remain poorly understood. These dimensions were evaluated in a
      population of 52 insulin-dependent diabetic adolescent girls and compared with
      evaluations of matched subjects from the general population. Results showed that
      the occurrence of anorexia nervosa is rare, the occurrence of unspecified eating
      disorders is frequent (35%) and the occurrence of bulimia nervosa is nearly six
      percent. Poor metabolic control as reflected in blood levels of glycosylated
      hemoglobin (HBA1C) was found in bulimic subjects and a tendency to be overweight
      was found in subjects with an unspecified eating disorder. Since such disorders
      frequently involve dietary restrictions, the role of a restrictive pattern in the
      occurrence of eating disorders is raised.

PMID- 8306234
TI  - [Role of the family in the development of borderline personality disorder].
AB  - The role of family in the development of borderline personality disorder is
      examined with an emphasis on dimensions of family functioning. A synthesis of
      theoretical concepts implicating such factors, derived mostly from
      psychoanalysis, is proposed with an emphasis on separation-individuation, early
      frustrations, regression to recognition memory, oscillations in attachment and
      social influences. Empirical studies are reviewed. Affective neglect and parental
      overprotection are often cited, although dysfunctional behaviour control may have
      a regulatory effect on these factors and a crucial impact on psychic reality of
      the patient recalling his childhood.

PMID- 8306235
TI  - Stability of positive and negative symptoms in schizophrenia.
AB  - Fifty-nine DSM-III-R schizophrenic outpatients were assessed for positive and
      negative symptoms using Andreasen's Scale for Assessment of Positive Symptoms
      (SAPS) and the Scale for Assessment of Negative Symptoms (SANS). Reevaluation of
      these patients 12 months later revealed a moderate degree of stability for both
      SAPS and SANS total scores and most of their subscales. Only the subscale scores
      for apathy and bizarre behaviour failed to show a significant correlation in
      stability in 12 months. The results are discussed in the context of the reported
      literature.

PMID- 8306236
TI  - Assessing psychopathology in Korean immigrants: some preliminary results on the
      SCL-90.

PMID- 8306237
TI  - Perception of body image.

PMID- 8306238
TI  - Substance abuse treatment for psychiatric patients.

PMID- 8306239
TI  - Viral infections and psychiatric illness.

PMID- 8306240
TI  - The multiplicity of actions of benzodiazepine receptor ligands.
AB  - The benzodiazepine receptor is an allosteric modulatory site present on most, if
      not all, gamma-aminobutyric acid A (GABAA) receptor channels (GABAA-R). The
      benzodiazepine receptor recognizes a large spectrum of compounds from different
      chemical classes that are grouped together as benzodiazepine receptor ligands--of
      benzodiazepine and non benzodiazepine structure. The GABAA-R is thought to be a
      heteropentameric protein complex composed of at least three different classes of
      subunits, with each subunit comprised of up to six structural variants. Binding
      of GABA to the extracellular domain of the receptor causes a conformational
      change that opens the channel pore to anions. A classical benzodiazepine achieves
      a positive allosteric modulation of the GABA channel gating function by
      increasing the affinity of the receptor for GABA and, possibly, by facilitating
      the conformational transition from the closed to the open form (benzodiazepine
      receptor agonists). Inverse agonists of benzodiazepine receptors cause negative
      allosteric modulation (a decrease in the GABA activity). Benzodiazepine receptor
      antagonists bind to the benzodiazepine receptor with little effect on GABAA-R
      functioning. The intrinsic efficacy of benzodiazepine receptor ligands determines
      the direction and magnitude of allosteric modulation. Benzodiazepine receptor
      agonists affect neuronal activity in all major neuronal networks. The classical
      pharmacological profile of benzodiazepine receptor agonists consists of
      anxiolytic, anticonvulsant, sedative, and myorelaxant activities. Partial
      agonists of benzodiazepine receptors conserve anxiolytic and anticonvulsant
      activity, with greatly reduced sedation and muscle relaxation. They promise to
      present therapeutic advantages, in particular for long term use. In initial
      studies. they have produced fewer side-effects and showed reduced tolerance
      development and physical dependence liability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306241
TI  - A double-blind randomized clinical trial of rapid tranquilization with I.M.
      clonazepam and I.M. haloperidol in agitated psychotic patients with manic
      symptoms.
AB  - This double-blind clinical trial studied 16 acutely agitated psychotic patients
      with manic or manic-like symptoms who needed rapid tranquilization and were
      therefore on maintenance treatment. They were randomized to receive intramuscular
      preparations of clonazepam (1 to 2 mg) or haloperidol (5 to 10 mg) at 0, 0.5, and
      1.0 hours. Both medications produced significant reduction of manic symptoms
      within two hours of initial treatment; however, haloperidol produced beneficial
      results more rapidly than clonazepam. All patients completed the study, with the
      exception of one haloperidol-treated patient who developed severe parkinsonism.
      It was concluded that I.M. clonazepam is an effective, safe, but slower-acting
      alternative to I.M. haloperidol in the treatment of agitated psychiatric patients
      in need of rapid tranquilization.

PMID- 8306242
TI  - Preclinical studies with radiolabeled monoclonal antibodies for treatment of
      patients with B-cell malignancies.
AB  - BACKGROUND: Studies on radiolabeled monoclonal antibodies (MoAb) have dealt
      mainly with single antibodies. However, major differences may exist among
      different radiolabeled MoAb that bind to the same antigen and between switch
      variants of the same antibody. This study evaluates and compares a series of
      radiolabeled MoAb of different specificities, subclasses, and isotypes applicable
      in treatment of patients with B cell malignancies. METHODS: MoAb were iodinated
      with iodogen. Immunoreactivity was determined in cell binding assays. Scatchard
      analyses were performed to determine association constants of radiolabeled MoAb
      and to measure antigen density on malignant B cells in various differentiation
      stages. The fate of the MoAb after antigen binding in vitro was studied by
      modulation and internalization experiments. RESULTS: All MoAb tested could be
      iodinated efficiently and displayed association constants of 0.9 x 10(9)M-1 or
      higher. Immunoreactivity of radiolabeled MoAb ranged from 62-79%, except for the
      immunoglobulin (Ig)-M MoAb CLB-MD20.2, which had an immunoreactivity of 43%. The
      highest number of binding sites was detected for the CD20 MoAb (12 x 10(3) - 355
      x 10(3), whereas the expression of antigens recognized by the CD22 MoAb was
      lowest on all cell types tested (4 x 10(3) - 26 x 10(3)). The MoAb CD19 and CD22
      both induced modulation, whereas the CD20 MoAb did not. Modulation induced by the
      CD19 MoAb was caused by internalization. The rate of internalization was isotype
      dependent and, for CD19-IgG1, partly mediated by Fc gamma ReceptorII.
      CONCLUSIONS: Radiolabeled B cell MoAb tested in this study are promising for use
      in radioimmunotherapy. For therapy with the radioisotope iodine-131, the IgG2a
      and IgG2b CD19 MoAb are more suitable than CD19-IgG1, because of their slower
      modulation and internalization rate.

PMID- 8306243
TI  - Comparative toxicity studies of yttrium-90 MX-DTPA and 2-IT-BAD conjugated
      monoclonal antibody (BrE-3).
AB  - BACKGROUND: BrE-3 is monoclonal antibody that has promise for imaging and therapy
      of human adenocarcinoma. Because of observations in therapeutic trials of yttrium
      90 (90Y) escape from radioimmunoconjugates and uptake by the skeleton with
      resultant bone marrow toxicity, the authors attempted to evaluate the importance
      of this factor by a comparison of the LD50 in healthy mice treated with 90Y that
      had been chelated with either of two high affinity chelators,
      methylbenzyldiethylene-triaminepentaacetic acid (MX-DTPA) or bromoacetamidobenzyl
      1,4,7,10-tetraazocyclododecane- N,N',N'',N'''-tetraacetic acid (BAD). METHODS AND
      RESULTS: Bone marrow hematopoietic toxicity was dose-limiting and the source of
      death for both chelators. The LD50 for 90Y-BrE-3-MX-DTPA was 220.9 microCi, and
      that for 90Y-BrE-3-2IT-BAD and was 307.8 microCi. Whole-body autoradiography
      revealed substantially greater uptake of 90Y in the skeleton when MX-DTPA was
      used as the chelator. CONCLUSIONS: These observations suggest that 90Y escape to
      bone is a significant factor in the maximum tolerated dose of
      radioimmunoconjugate that can be used in therapeutic trials. These results
      probably underestimate the importance of 90Y escape since 90Y in the skeleton of
      patients is likely to be more significant than in mice because more of the 90Y
      energy is absorbed in the marrow of larger species.

PMID- 8306244
TI  - The biologic window for chimeric L6 radioimmunotherapy.
AB  - BACKGROUND: There has been little success in using radioimmunotherapy in patients
      with adenocarcinoma, partly because of the low tumor uptake of the administered
      monoclonal antibody (MoAb). The authors recently reported therapeutic response in
      advanced cancer patients who received 131I chimeric-L6 MoAb. The L6 MoAb
      identifies abundant, nonshed antigen that is expressed in many human carcinomas,
      including carcinomas of the lung, breast, colon, and ovary. In vitro both mouse
      L6 (L6) and chimeric L6 (ChL6) mediate complement-dependent tumor cytolysis with
      human serum, and antibody-dependent tumor cell cytolysis with normal human
      peripheral blood mononuclear cells. The authors have used L6 or ChL6 for
      radioimmunotherapy to exploit their biologic activity to create a "therapeutic
      window" of increased vascular permeability, allowing more 131I MoAb to reach the
      tumor. A reactive target is present in the vascular endothelium but can be
      covered by unlabeled L6 or ChL6. METHODS: Nine patients with metastatic breast
      cancer were treated on a therapy protocol and received imaging and therapy doses
      of 131I ChL6 on two sequential days at 4 week intervals. During each treatment
      cycle, serum cytokines, complement, albumin, and 131I ChL6 blood clearance were
      monitored, peripheral blood mononuclear cell activation was assessed, and tumor
      uptake and response were documented. RESULTS: After L6 or ChL6 was infused,
      patients demonstrated immediate serum-complement activation, manifested by
      rapidly decreasing levels of serum complements 3 and 4. Tumor uptake of the
      second 131I MoAb (therapeutic) injection, given after the second daily injections
      of 200 mg MoAb, was usually higher than the tumor uptake of the first 131I MoAb
      (imaging) dose given after a single 200 mg infusion of MoAb. Although serum
      complement frequently decreased after the first 50-100 mg dose of L6 or ChL6,
      elevation of soluble interleukin-2 receptor (IL-2R) in serum was seen only in
      patients who received 150 mg or more of L6 or ChL6. In the nine treated patients,
      with only one exception, the higher grade of therapeutic tumor response was seen
      in patients with a greater increase in IL-2R levels. CONCLUSIONS: The clinical
      importance of understanding these mechanisms is emphasized by the occurrence of
      measurable tumor regressions in five of the first nine advanced metastatic breast
      cancer patients treated in this manner. Absence of pulmonary edema and delayed
      release of dose-dependent IL-2R suggest that targeting of the pulmonary
      endothelium by L6 or ChL6 is not the major cause of the observed biologic
      effects. This unique response of a solid tumor to radioimmunoconjugate therapy
      may be secondary to both the increased delivery of the radioimmunoconjugate to
      tumor cells caused by enhanced vascular permeability, and to synergistic effects
      of radiation and activated effector cell mechanisms.

PMID- 8306245
TI  - A general extracorporeal immunoadsorption method to increase tumor-to-tissue
      ratio.
AB  - The idea of applying extracorporeal immunoadsorption (ECIA) in
      radioimmunodiagnosis and radioimmunotherapy has been proposed previously. The
      authors here report on the development of new concept using a general method for
      ECIA based on biotinylated MoAb adsorbed on an avidin column. Athymic rats
      heterotransplanted with either human melanomas or human lung carcinoma were
      injected with iodine-125-labeled biotinylated 96.5 or L6 MoAb, respectively. At
      24 or 48 hours after the injection, ECIA was performed by pumping blood through a
      hollow-fiber plasma filter. The separated plasma then was passed through an
      absorbent (avidin-agarose) column. The whole ECIA procedure lasted for 3 hours.
      By this ECIA method, the tumor-to-normal tissue ratios were increased in various
      tissues (i.e., radiosensitive and blood rich organs) by a factor of four to five.

PMID- 8306246
TI  - Overview of radiation myelotoxicity secondary to radioimmunotherapy using 131I
      Lym-1 as a model.
AB  - The radiation dose-limiting toxicity from radioimmunotherapy has been
      myelotoxicity in the absence of bone marrow reconstitution (transplantation).
      Myelotoxicity can be assessed directly by biopsy examination of the bone marrow
      and indirectly by peripheral blood counts. In patients with B-cell malignancies,
      thrombocytopenia has been the initial and most severe manifestation of 131I-Lym-1
      radiation toxicity from treatment. Manifestations of myelotoxicity varied greatly
      among the patients and from one treatment dose to another in the same patient,
      suggesting that additional factors were present. There was an increased
      likelihood of Grade 3-4 hematopoietic toxicity after 131I-Lym-1 treatment if the
      patient had peripheral blood cell abnormalities before undergoing 131I-Lym-1
      treatment. Fractionation of the total 131I-Lym-1 dose was associated with less
      toxicity. In many patients, myelotoxicity could not be explained by marrow
      radiation dose (0.36 +/- 0.13 rads per administered mCi) from 131I-Lym-1 in the
      blood and body alone. Bone marrow examination and 131I-Lym-1 imaging usually
      provided evidence for additional marrow radiation from 131I-Lym-1-targeting of
      marrow malignancy and also for residual toxic effects from prior treatment in
      these patients. Immunohistologic and imaging examination of the bone marrow
      performed with the intended treatment antibody allowed assessment of extent of
      marrow malignancy and prediction of degree of myelotoxicity from subsequent
      treatment. Treatment programs (and protocols) for radioimmunotherapy should
      incorporate these methods into the decision process. Larger amounts of 131I-Lym-1
      can be used in patients selected to have relatively normal peripheral blood cell
      counts and normocellular bone marrows uninvolved by the malignancy. These
      observations appear to be relevant to the maximum tolerated dose in
      radioimmunotherapy for other malignancies as well.

PMID- 8306247
TI  - Murine and humanized constructs of monoclonal antibody M195 (anti-CD33) for the
      therapy of acute myelogenous leukemia.
AB  - Long-term survival rates of patients with acute myelogenous leukemia treated with
      intensive chemotherapy are 15-20%, despite efforts to develop new treatment
      strategies. Murine M195 (131I-M195), an anti-CD33, immunoglobulin (Ig) G2a
      monoclonal antibody has reactivity restricted to early myeloid cells and myeloid
      leukemic blasts but not hematopoietic progenitors. Previous trials in patients
      with relapsed or refractory myeloid leukemia showed that 131I-M195 rapidly
      targeted to the bone marrow and internalized into target cells. This article
      describes a therapeutic dose escalation study in which 24 patients received from
      50 mCi/m2 to 210 mCi/m2 of 131I-M195 in divided doses. Cytoreduction of
      peripheral cell counts and bone marrow blasts occurred without nonhematopoietic
      toxicity. Doses of 131I-M195 greater than 135 mCi/m2 were associated with marrow
      cytoreduction sufficient to necessitate bone marrow transplant. However, 37% of
      the patients developed human anti-mouse antibody, preventing retreatment. To
      decrease immunogenicity and improve effector function, chimeric IgG1 and IgG3,
      and complementarity-determining region-grafted, humanized IgG1 and IgG3 versions
      of mouse M195 were developed by genetic engineering techniques. The new versions
      maintained specificity and biologic function, and they were superior to the mouse
      M195 in their ability to perform antibody-dependent cellular cytotoxicity against
      leukemia cells. Humanized M195, but not chimeric M195, showed a 4-8.6 times
      higher avidity than its mouse counterpart. Because effector function of IgG
      depends to a large extent on Fc clustering, a homodimeric HuG1 also was
      developed. Homodimeric HuG1 showed an ability to cause additional dramatic
      improvements in effector functions, as well as an ability to internalize and
      retain radioisotope in target leukemia cells. Monomeric and dimeric forms of
      humanized M195 may be advantageous in the therapy of acute myelogenous leukemia.

PMID- 8306248
TI  - Phase II radioimmunotherapy trial with 131I-CC49 in colorectal cancer.
AB  - BACKGROUND: Radiolabeled CC49, a second generation high affinity monoclonal
      antibody (MoAb) reactive with tumor-associated glycoprotein 72 (TAG72) has
      undergone previous Phase I testing in patients with colon cancer. Based on this
      report, the authors treated 15 refractory metastatic colon cancer patients with
      131I-CC49 to determine its overall toxicity and the response to therapy of
      patients treated with it. METHODS: Patients received 75 mCi/m2 131I-CC49 (20 mg
      MoAb) intravenously for a period of 30-60 minutes. Whole body retention was
      derived from the measured dose-rate of I-131 monitored daily at 1 m using an ion
      chamber. Two whole-body and static-gamma camera images were taken of patients on
      days 4 and 7 after the infusion. RESULTS: Nonhematologic toxicity (Grade 1-2)
      consisted of nausea (two patients), arthralgias (three patients), transient fever
      and chills (two patients), and transient blood pressure changes (two patients).
      At 4-5 weeks posttreatment, reversible Grade 3-4 thrombocytopenia was observed in
      7 of 15 patients, and reversible Grade 3-4 granulocytopenia was observed in 6 of
      15 patients. Twelve of 13 patients tested developed human anti-mouse antibody
      (range, 161 to > 20,000 ng/ml) at 6-8 weeks postinfusion. Mean +/- SD whole-body
      half-life (whole-body retention) of 131I-CC49 was 57.3 +/- 13.4 hours. Tumors
      were seen in all patients. In two of three patients treated a second time, an
      increased whole body clearance rate correlated with elevated human anti-mouse
      antibody, reduced uptake in tumor, and enhanced uptake in the thyroid. Estimated
      tumor doses ranged from 19-667 rads. Red marrow dose estimated from whole body
      retention ranged from 60 to 117 rads and correlated with decreases in platelet
      count. No objective tumor responses (i.e., partial or complete) were observed.
      CONCLUSIONS: Despite minimal toxicity and favorable tumor uptake, efficacy has
      been limited at this dose and schedule.

PMID- 8306249
TI  - Pharmacokinetics and toxicity of an yttrium-90-CITC-DTPA-HMFG1
      radioimmunoconjugate for intraperitoneal radioimmunotherapy of ovarian cancer.
AB  - BACKGROUND: The intracavitary route for the administration of monoclonal
      antibodies is used in a variety of locally spreading cancers. The authors have
      been treating patients with ovarian cancer in Phase I and II studies assessing
      toxicity and response to improved radioimmunoconjugates. METHODS: Nineteen
      patients, 34-65 years of age, were treated with a new radioimmunoconjugate, 90Y
      CITC-DTPA-HMFG1, instilled in the peritoneal cavity after second-look
      laparoscopy. Activity was increased in a stepwise fashion. RESULTS: Following the
      intraperitoneal administration of 90Y-CITC-DTPA-HMFG1, levels of the
      radioimmunoconjugate in the blood increased, reaching a peak of about 30% of
      injected activity at around 54 hours posttreatment. Approximately 18% of the
      radiolabel was excreted in the urine within 96 hours. Bone-marrow toxicity was
      the dose-limiting factor. Grade III platelet and granulocyte toxicity was
      observed at 19.3 mCi/m2. A type III immunologic response was observed in a number
      of patients. CONCLUSIONS: A dose of 18.5 mCi/m2 for subsequent treatments is
      recommended, based on a linear correlation of activity dose-to-body surface area.
      The clinical profile of a mild to moderate hypersensitivity syndrome is presented
      and hypotheses regarding its etiology are suggested.

PMID- 8306250
TI  - Intralesional radioimmunotherapy of malignant gliomas. An effective treatment in
      recurrent tumors.
AB  - BACKGROUND: Intralesional radioimmunotherapy (RAIT) may improve the management of
      malignant gliomas whose prognosis is, at present, very poor. Current treatment
      modalities (e.g., surgery, radiotherapy, and chemotherapy) may prolong survival
      by a few months but cannot prevent tumor recurrence. METHODS: Following one or
      more surgical operations, radiotherapy, and chemotherapy, 24 patients with
      recurrent malignant gliomas (23 brain and 1 spinal cord) underwent RAIT with 2
      murine monoclonal antibodies (MoAb), BC-2 and BC-4, raised against tenascin (TN).
      This antigen is expressed in large amounts in the stroma of glial tumors but not
      normal brain tissue. The isotope used was iodine-131 (131I). The radiolabelled
      antibodies were injected directly into the tumor by means of a removable catheter
      or an indwelling catheter placed in the site of disease at the time of
      craniotomy. The patients were admitted to the protocol if histochemical analysis
      of their tumors demonstrated the presence of TN in high abundance.
      Biodistribution and dosimetry of an intralesional tracer dose (1 mg MoAb and 37
      MBq 131I) were studied. RAIT was performed by the administration of escalating
      doses of radioiodine, ranging from 15 mCi to 57 mCi. In many cases, RAIT was was
      repeated two, three, or four times (on 8, 3 and 4 patients, respectively).
      RESULTS: Pharmacokinetic data resulted, on average, as follows: the 24-hour
      tumor/background ratio was 16.6; the percentage of injected dose concentrated per
      gram of tumor at 24 hours was 2.4%; and the effective half-life of the MoAb at
      the tumor was 74.5 hours. The mean radiation dose to the tumor was 36.48 cGy per
      MBq of 131I injected. Both systemic and brain toxicities were absent, while human
      anti-mouse antibody production after MoAb administration occurred in only a few
      cases. At present, 17 patients are assessable, with a median survival time of 16
      months. Objective responses consisted of 5 tumor stabilizations (median time, 9
      months), 3 partial remissions (11 months), and 3 complete remissions (15 months).

PMID- 8306251
TI  - Cytokine intervention permits dose escalation of radioantibody. An analysis of
      myelostimulation by bolus versus continuous infusion of IL-1/GM-CSF.
AB  - BACKGROUND: The authors recently reported that a 12-day schedule (beginning 3
      days before radioantibody treatment) of twice-daily dosing of rH-IL-1 (1 x 10(3)
      U/dose) and rM-GM-CSF (0.5 micrograms/dose) can reduce the magnitude and duration
      of radioantibody-induced myelosuppression, thereby permitting a 25-30% increase
      in the dose of radioantibody that can be administered without the dose proving
      lethal. In an effort to further reduce toxicity and escalate the tolerated dose,
      the authors altered the method of administration of cytokines from daily bolus
      dosing to continuous infusion by implantable osmotic pumps. METHODS: A control
      group of mice was compared to five groups of mice that either did or did not
      receive a 340 microCi dose of radioantibody, and received no cytokines, cytokines
      by bolus dosing, or cytokines by continuous infusion. For 4 weeks, peripheral
      white blood cell and thrombocyte counts and thymus and spleen weights were taken,
      marrow cell number was monitored, and marrow colony-forming unit activity was
      evaluated weekly in the untreated control mice and the treated mice. RESULTS:
      These studies demonstrated that after a dose of radioantibody, continuous dosing
      of cytokines resulted in higher white blood cell (WBC) and platelet values than
      if bolus delivery was used (day 7, WBC: 110% vs. 59%; day 14, WBC: 85% vs. 62%;
      day 21, WBC: 98% vs. 42%; day 7, platelets: 122% vs. 51%; day 14, platelets: 159%
      vs. 72%; day 21, platelets: 239% vs. 171%). A comparison of bolus versus
      continuous dosing in the absence of radioantibody indicated that spleen weight
      increased by 40-60% after continuous infusion of cytokines and by 20-25% after
      bolus dosing. The 20-30% decrease in thymus weight was similar with both dosing
      regimens. Colony-forming units (CFUs) in marrow increased from 30-35 in untreated
      mice to 50-55 in mice given cytokines by bolus injection, and to 150-180 in mice
      given continuous infusion of cytokines. Spleen CFUs exhibited an insignificant
      increase after bolus dosing of cytokines but increased almost fourfold after
      continuous dosing. Peak stimulation of marrow and spleen CFUs occurred 28 days
      after initiation of cytokine administration (2 weeks after cytokines
      administration was stopped). The probability of survival for 6 weeks after
      further dose escalation to 360 microCi I-131-MN-14 immunoglobulin G was 16.4% +/-
      8.6% after bolus dosing and 58.1% +/- 11.3% after continuous infusion of
      cytokines. CONCLUSIONS: Although continuous infusion of cytokines proved to be a
      better method of reducing hematopoietic toxicity, further dose escalation of
      radioimmunotherapy using the "pump" method of cytokine delivery was not possible.
      Cytokine intervention by either mode of delivery permits a 25% dose
      intensification without the dose becoming lethal. Further escalation is not
      feasible, possibly because of other end organ toxicity.

PMID- 8306252
TI  - Human anti-mouse antibody suppression with cyclosporin A.
AB  - BACKGROUND: Cyclosporin was used in an attempt to suppress the formation of human
      antimouse antibody (HAMA) after administration of murine monoclonal antibodies.
      METHODS: Thirteen patients were given oral cyclosporin (8.6-15 mg/kg/day)
      starting 2 days before administration of technetium-99m (99mTc) labeled F(ab')2
      (3 patients) or Fab (10 patients) murine antibody fragment. Six to nine days
      later, patients received either rhenium-186 (186Re)-labeled F(ab')2 or an intact
      antibody. Cyclosporin was continued for 14 days after the second antibody
      administration. RESULTS: Five patients (38%) did not develop elevated HAMA titers
      for up to 8 weeks after antibody administration. These five patients had a median
      cyclosporin concentration of 726 ng/ml, while the eight patients who developed
      HAMA had a median cyclosporin level of 364 ng/ml. In contrast, when not given
      cyclosporin, 86% (24/28) of patients developed HAMA after receiving two doses of
      F(ab')2, and 100% (15/15) developed HAMA after receiving Fab followed by intact
      antibody. Toxicity from cyclosporin included elevation concentrations of
      bilirubin and creatinine, and increased blood pressure, which rapidly resolved
      after the cyclosporin was discontinued. CONCLUSIONS: This study demonstrates that
      cyclosporin given from 2 days before until 2 weeks after administration of either
      a F(ab')2 or intact murine antibody can suppress HAMA formation. This strategy
      may permit administration of repeated doses of murine-antibody-based
      radioimmunotherapy.

PMID- 8306253
TI  - Human monoclonal antibody developed against ovarian cancer cell surface antigen.
AB  - BACKGROUND: Murine monoclonal antibodies (MoAb) potentially can be used in the
      radioimmunodetection and radioimmunotherapy of cancer. However, the
      administration of these radiopharmaceuticals to humans often leads to induction
      of human anti-murine antibodies (HAMA). HAMA has many disadvantages, which could
      decrease efficacy of the murine MoAb. The purpose of this work was to produce
      human monoclonal antibody against a human ovarian cancer cell surface antigen
      (OCCSA), which was not present in normal ovarian cells. This 200-kilodalton OCCSA
      also was used in the present study for characterizing the human monoclonal
      antibody. METHODS: Human monoclonal antibodies were produced in vitro by fusion
      of mutant myeloma cells, selected from GM1500, with human lymphoid cells
      immunized in vitro with purified OCCSA: The human monoclonal antibody was
      characterized using the following techniques: sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), native-PAGE, Western blotting
      followed by protein-A gold staining, immunodiffusion assays, and fluorescent
      antibody assays. RESULTS: Human monoclonal antibody, TC5 (immunoglobulin G1), was
      produced and purified. It was found to be specific for ovarian cancer, while also
      reacting with an early stage breast cancer. TC5 did not react with any normal
      (i.e., nonneoplastic) cells of the ovary, uterus, cervix, endocervix, or
      fallopian tube, nor did it react with normal lung, heart, pancreas, liver, or
      breast tissue. CONCLUSION: Human-human hybridomas produced human monoclonal
      antibody against OCCSA: The human monoclonal antibody, TC5, was specific for
      ovarian and breast cancer. TC5 did not react with any normal tissue tested.
      Future work will focus on the in vivo characterization of the human monoclonal
      antibody, after labeling with radionuclides.

PMID- 8306254
TI  - Potential for recombinant immunoglobulin constructs in the management of
      carcinoma.
AB  - BACKGROUND: Numerous monoclonal antibodies (MoAb) have been developed and
      currently are being evaluated in both diagnostic and therapeutic clinical trials.
      Despite the major advances fostered by MoAb technology, several limitations
      inherent to the use of MoAb exist. For example, MoAb may not have the desired
      plasma pharmacokinetics and metabolic properties, and they may be immunogenic,
      thus reducing the possibility of numerous administrations. METHODS: Recombinant
      DNA technology is used to develop (1) mouse-human chimeric antibodies in which
      the constant region of a murine antibody is replaced with the human constant
      region, (2) chimeric antibodies with domain-deletions or alterations in
      glycosylation, and (3) sFv molecules, i.e., recombinant proteins composed of a VL
      amino acid sequence of an immunoglobulin tethered to a VH sequence by a designed
      peptide. RESULTS: This article reviews some of the genetic modifications that can
      be made with recombinant or chimeric immunoglobulin forms; two anti-TAG-72 MoAb,
      B72.3 and CC49, are used as examples. The immunoglobulin molecules that have been
      generated include those with alterations of subclass, domain deletions, and
      glycosylation, as well as those sFv molecules that have been prepared. The
      immunochemical and biologic properties of these novel immunoglobulin forms are
      described. CONCLUSIONS: Recombinant DNA technology makes feasible the development
      of novel immunoglobulin forms. These genetic modifications may result in more
      useful diagnostic reagents and in the production of more stable immunoconjugates
      with the characteristics of more efficient tumor cell killing.

PMID- 8306255
TI  - Galactosylated antibodies and antibody-enzyme conjugates in antibody-directed
      enzyme prodrug therapy.
AB  - Antibody directed enzyme prodrug therapy (ADEPT) has been studied as a two- and
      three-phase system in which an antibody to a tumor-associated antigen has been
      used to deliver an enzyme to tumor sites where it can convert a relatively
      nontoxic prodrug to a cytotoxic agent. In such a system, it is necessary to allow
      the enzyme activity to clear from the blood before prodrug injection to avoid
      toxicity caused by prodrug activation in plasma. To accelerate plasma clearance
      of enzyme activity, two approaches have been studied. The studies have been
      performed with a monoclonal anticarcinoembryonic-antigen antibody fragment A5B7
      F(ab')2 conjugated to a bacterial enzyme, carboxypeptidase G2 (CPG2), in LS174T
      xenografted mice. In the first approach, a monoclonal antibody (SB43), directed
      at CPG2, was used, which inactivates CPG2 in vitro and in vivo. SB43 was
      galactosylated so that it had sufficient time to form a complex with plasma CPG2,
      resulting in the inactivation and clearance of the complex from plasma via the
      carbohydrate-specific receptors in the liver. Injection of SB43gal 19 hours after
      administration of the radiolabeled conjugate reduced the percentage of injected
      dose per gram in blood without affecting levels in the tumor. The second approach
      involved galactosylation of the conjugate so that it cleared rapidly from blood
      via the asialoglycoprotein receptors in the liver. Localization of the
      radiolabeled conjugate was achieved by blocking this receptor for about 8 hours
      with a single injection (8 mg/mouse) of an inhibitor that binds competitively to
      the receptor. This allowed tumor localization of the conjugate followed by a
      rapid clearance of the galactosylated conjugate from blood as the inhibitor was
      consumed. A tumor-to-blood ratio of 45:1 was obtained at 24 hours, which
      increased to 100:1 at 72 hours after the conjugate injection. These accelerated
      clearance mechanisms have been applied in antitumor studies in ADEPT.

PMID- 8306256
TI  - Activating anti-idiotypic human anti-mouse antibodies for immunotherapy of
      ovarian carcinoma.
AB  - Human anti-mouse antibodies (HAMA) are observed frequently after
      immunoscintigraphy with monoclonal antibodies (MoAb) directed against CA-125. As
      the authors have shown previously, HAMA can cause false-positive CA-125 values in
      routine CA-125 immunoradiometric assay (IRMA) tumor-marker assays (in one case,
      up to 900 days after immunoscintigraphy). In 32 patients, the authors found a
      HAMA frequency of 34% (11/32: 3/7 after the first administration, 6/13 after the
      second, and 2/2 after the third). Ten patients developed extremely high CA-125
      levels after undergoing the CIS IRMA assay (up to 80,000 U/ml) in parallel to a
      significant HAMA increase. The use of different assays, or HAMA removal before in
      vitro testing, can solve this problem. After a new CA-125 assay containing
      antibodies that recognize different epitopes on the CA-125 antigen (Biomira Tru
      Quant OV) was applied, only mildly increased assay results or normal levels were
      measured. Most of HAMA-positive patients demonstrated a predominantly anti
      idiotypic response, determined with two different HAMA assays. Seven patients
      with anti-idiotypic HAMA responses after OC-125 immunoscintigraphy remained free
      of tumor or had stable disease (2-42 or more months), contrary to their poor
      prognoses that had been made based on the underlying stages of their tumors. All
      of these patients are currently doing well (Karnofsky Index > 70%) and show no
      significant tumor progression. In light of their extremely poor prognoses (5-year
      survival rates of 3-5% in recurrent International Federation of Gynecology and
      Obstetrics III/IV stages), without further chemotherapy, these courses are
      extremely unusual. Preliminary in vitro experiments lead to the postulation that
      anti-idiotypic HAMA may trigger an antitumor effect either by suppressing the
      growth of CA-125-expressing cancer cells directly, or by activating the patient's
      immune response via induction of Ab3. Similar results are observed after
      immunoscintigraphy with a technetium-99m-labeled anti-CA-125 monoclonal antibody
      (B43.13), which the authors now also use for immunotherapy of ovarian cancer
      patients by repeated injections, hoping that induction of anti-idiotypic HAMA
      will be beneficial for prolonged survival of patients with ovarian carcinoma.

PMID- 8306257
TI  - Technetium-99m, rhenium-186, and rhenium-188 direct-labeled antibodies.
AB  - BACKGROUND: Antibody sulfhydryl groups can act as effective carriers of reduced
      technetium and rhenium species for radioimmunodetection and radioimmunotherapy.
      METHODS: Intact immunoglobulin G and fragments were labeled with the isotopes and
      examined in vitro and in vivo. RESULTS: Technetium bound to intact immunoglobulin
      G was found to be the most stable species in vitro, but in vivo, clearances of
      technetium and rhenium bound to intact antibody were similar. Serum clearances
      were faster than those seen for the corresponding radioiodinated antibodies. In
      vivo clearance rates of the radiolabeled fragments were similar, with kidney
      uptake and retention seen. Rhenium-labeled antibodies, despite a greater tendency
      toward in vitro reoxidation than technetium-labeled antibodies, did not show
      enhanced kidney clearance in animal models. Rhenium-188 and technetium-99m were
      obtained from similar generator systems in carrier-free form. Using rhenium-188
      spiked with cold rhenium, it was determined that approximately one rhenium atom
      per molecule of antibody can be conjugated directly. Rhenium-186 also was coupled
      at almost a 1:1 ratio to antibody. CONCLUSIONS: Only radiolysis concerns will
      limit the amount of rhenium-188 conjugated to antibody. Large doses of antibody
      will be necessary to deliver rhenium-186 at this isotope's currently available
      specific activity. Otherwise, higher specific activity rhenium-186, and/or
      greater loading capacity of rhenium-186 onto antibody, will be needed to generate
      the type of product that will be usable at a clinical dose of several hundred
      millicuries.

PMID- 8306258
TI  - A peptide-based bifunctional chelating agent for 99mTc- and 186Re-labeling of
      monoclonal antibodies.
AB  - BACKGROUND: The development of new bifunctional chelating agents for the labeling
      of monoclonal antibodies with radiometals is a desirable goal in the area of
      radioimmunodetection and radioimmunotherapy of cancer. The authors have developed
      a new N3S-ligand, N-(S-acetylmercaptoacetyl) (p-NCS)phenylalanylglycylglycine
      ethyl ester (MAIPGG) for technetium-99m (99mTc) or rhenium-186 (186Re) labeling
      of monoclonal antibody D612 reactive with human colon cancer. The biodistribution
      of 99mTc/186Re-MAIPGG-D612 conjugates was studied in nude mice bearing human
      colon cancer xenografts. METHODS: MAIPGG was synthesized from Boc-p
      nitrophenylalanine and was coupled to antibody D612, and the conjugate was
      labeled with 99mTc using a Glucoscan kit (DuPont, North Billerico, MA) as the
      reducing system. 186Re-MAIPGG-D612 was prepared by radiolabeling MAIPGG with
      186Re, with sodium citrate/SnCl2 used as a reducing system, after which the
      raiolabeled MAIPGG was coupled to monoclonal antibody D612. The biodistribution
      of these radioimmunoconjugates in athymic nude mice bearing LS174T human colon
      cancer xenografts was studied. RESULTS: The cold precursor MAIPGG was prepared
      easily from Boc-p-nitro phenylalanine with an overall yield of 12-15%, which,
      when coupled to monoclonal antibody D612, did not affect its binding activity to
      LS174T cells in vitro. The biodistribution and imaging results demonstrated that
      these radioimmunoconjugates localized preferentially in tumor. CONCLUSIONS: These
      preliminary results suggest that MAIPGG may be useful for the radiolabeling of a
      variety of monoclonal antibodies with 99mTc or 186Re, which then can be used for
      radioimmunodetection and radioimmunotherapy of cancer.

PMID- 8306259
TI  - Production of no-carrier-added 64Cu from zinc metal irradiated under boron
      shielding.
AB  - BACKGROUND: Positron emission tomography offers advantages for
      radioimmunodiagnosis of cancer but requires radionuclides of appropriate half
      life that have high specific activity and high radio-purity. This work was
      designed to develop a viable method to produce and purify 64Cu, which has high
      specific activity, for positron emission tomography. METHODS: 64Cu was produced
      at the University of Missouri Research Reactor by the nuclear reaction,
      64Zn(n,p)64Cu. Highly pure zinc metal (99.9999%) was irradiated in a specially
      designed boron nitrite lined container, which minimized thermal neutron reactions
      during irradiation. A new two-step procedure was developed to chemically separate
      the no-carrier-added 64Cu from the zinc metal target. RESULTS: 64Cu recovery for
      24 runs averaged 0.393 (+/- 0.007) mCi per milligram of zinc irradiated. The
      boron-lined irradiation container reduced unwanted zinc radionuclides 14.3-fold.
      Zinc radionuclides and non-radioactive zinc were separated successfully from the
      64Cu. The new separation technique was fast (2 hours total time) and highly
      efficient for removing the zinc. The zinc separation factor for this technique
      averaged 8.5 x 10(-8), indicating less than 0.0000085% of the zinc remained after
      separation. Thus far, the highest 64Cu specific activity at end of irradiation
      was 683 Ci/mg Cu, with an average of 512 Ci/mg Cu for the last six analyzed runs.
      CONCLUSION: The boron-lined irradiation container has sufficient capacity for 75
      fold larger-sized zinc targets (up to 45 g). The new separation technique was
      excellent for separating 64Cu, which appears to be a radionuclide with great
      potential for positron emission tomography.

PMID- 8306260
TI  - A comparative study of copper-67 radiolabeling and kinetic stabilities of
      antibody-macrocycle chelate conjugates.
AB  - BACKGROUND: The development of new chelating agents and radiolabeling protocols
      is essential to progress in radioimmunotherapy with antibody-chelate conjugates.
      METHODS: Immunoconjugates of four polyazamacrocycles with N-bonded acetate groups
      were prepared by conjugation via 2-iminothiolane to Lym-1, a murine antilymphoma
      immunoglobulin G2a MoAb. To optimize 67Cu radiolabeling, complexation conditions
      were explored. The kinetic stabilities in vitro in human serum of four 67Cu
      labeled immunoconjugates were investigated. RESULTS: Lym-1-2IT-6-BAT-67Cu, the
      chelate conjugate of 6-[p-(bromoacetamido)benzyl]-1,4,8,11
      tetraazacyclotetradecane- N,N',N''N'''-tetraacetic acid, exhibited excellent
      kinetic stability in human serum, while Lym-1-2IT-2-BAT-67Cu, prepared from the
      structural isomer 2-[p-(bromoacetamido)benzyl]-1,4,8,11- tetraazacyclotetradecane
      N,N',N'',N'''-tetraacetic acid, exhibited a markedly higher rate of loss of
      radiometal. It was observed that the radiolabeling ratio of Lym-1-2IT-6-BAT-67Cu,
      in mCi per mg immunoconjugate, was limited solely by the specific activity of the
      radiometal, which varied significantly from lot to lot. This ratio for a given
      lot of 67Cu can be predicted by a preliminary titration. CONCLUSIONS: The
      preparation of 67Cu labeled immunoconjugates of therapeutic quality has been
      improved by the determination of optimum radiolabeling conditions, and by
      development of a titration protocol which rapidly and accurately predicts the
      radiolabeling ratio in mCi per mg immunoconjugate. The surprising difference in
      the properties of 6-BAT and 2-BAT shows the exquisite dependence of kinetic
      stability on structure.

PMID- 8306261
TI  - Processing of antibody-radioisotope conjugates after binding to the surface of
      tumor cells.
AB  - BACKGROUND: Previous experiments indicated that most antibodies binding to cell
      surface antigens are internalized gradually and degraded within lysosomes, with a
      half-life of degradation of approximately 1 day, for most antibodies. The
      research discussed in this article extended our studies to eight additional
      antibodies reacting with six different antigens, including three antigens
      anchored in the membrane by glycosyl-phosphatidylinositol. The authors also
      tested antibodies labeled with 111indium, as well as 125iodine, to determine
      whether different radiolabels would be processed differently. METHODS: Antibodies
      were radiolabeled with 125I or with 111In bound to benzyl-DTPA. After binding to
      the surface of tumor cells in vitro, excess antibody was washed away, and the
      fate of the radiolabel was investigated over periods of 3-7 days. Radiolabel
      released into the supernatant or retained by the cells was analyzed to determine
      whether it was still on intact antibody. RESULTS: In 13 of the 15 antibodies that
      were tested, a similar pattern of irreversible binding and gradual catabolism was
      observed. Iodine conjugated to antibodies was released rapidly from the cell
      after antibody catabolism. In contrast, the 111In was retained within the cell
      much longer than 125I, with the rate of degradation and release into the medium
      being at least fivefold slower. More than 50% of the bound 111In was still
      present on the cells after 7 days. Biochemical analysis of the retained 111In
      extracted cells after 4-6 days demonstrated that it was no longer associated with
      antibodies and was in a low molecular weight form, probably still associated with
      the chelator benzyl-DTPA. CONCLUSIONS: Different radiolabels are processed by
      tumor cells differently, after catabolism of the antibody to which they
      originally were conjugated. The data suggest that the prolonged retention of
      111In, relative to that of 125I, is due not to deiodination of iodine conjugates,
      but rather to intracellular retention of catabolic products containing 111In,
      perhaps within lysosomes. The use of radioisotopes that are retained within cells
      after antibody internalization and degradation may improve both
      radioimmunodetection and radioimmunotherapy of cancer.

PMID- 8306262
TI  - The use of severe combined immunodeficiency mice to study the metabolism of human
      immunoglobulin G.
AB  - BACKGROUND: Although the four human immunoglobulin G (IgG) isotypes are similar
      in structure, they exhibit significant differences in effector function and
      catabolic half-life. With advent of structurally engineered antibodies, there is
      the potential to design antibody constructs with desired half-lives; however, it
      is first necessary to discover the structures and mechanisms that control
      immunoglobulin metabolism. METHODS: Radioiodinated chimeric antibodies,
      consisting of a mouse antidansyl variable region and the four human IgG constant
      regions, were injected intravenously into Balb/c and severe combined
      immunodeficiency (SCID) mice, and their half-lives were determined by whole body
      and whole blood counting. Dependence of the rate of immunoglobulin catabolism on
      immunoglobulin concentration, a normal regulatory phenomenon specific to IgG, was
      evaluated by the introduction of large amounts of human gamma-globulin
      intraperitoneally. RESULTS: Whole body and blood half-lives were statistically
      indistinguishable. The four IgG isotypes were eliminated from the whole animals
      in a predominantly single-phasic manner, with the half-life being dependent on
      the isotype studied. In Balb/c mice, immune elimination frequently occurred after
      6 days, although this was not observed in SCID mice. Relevance of the model was
      confirmed by the demonstration of the presence of the concentration-catabolism
      phenomenon, a relationship unique to normal IgG regulation. CONCLUSIONS: SCID
      mice provide an adequate initial animal model for the study of human-mouse
      chimeric antibodies. Further understanding of the factors governing
      immunoglobulin catabolism can be probed by study of recombinant human constant
      regions in this animal system.

PMID- 8306263
TI  - Distribution of 111In- and 125I-labeled monoclonal antibody 17-1A in mice bearing
      xenografts of human pancreatic carcinoma HuP-T4.
AB  - BACKGROUND: The prognosis of pancreatic adenocarcinoma still remains poor because
      of the lack of reliable diagnostic tests for early stages of the disease.
      Monoclonal antibody 17-1A (MoAb 17-1A) has been studied extensively, and the
      antigen recognized by MoAb 17-1A is expressed by adenocarcinomas of the pancreas
      and stomach, as well as other normal and malignant epithelial tissues. The
      potential of MoAb 17-1A was investigated for its ability to detect pancreatic
      carcinomas. The use of MoAb 17-1A in treatment also was studied. METHODS:
      Immunoreactivity of MoAb 17-1A with human pancreatic carcinoma cell line HuP-T4
      was examined histochemically by the avidin-biotinylated enzyme complex method.
      MoAb 17-1A was labeled with 125I by the Iodogen method and 111In using either
      diethylenetriaminepentaacetic anhydride (cDTPA) or 1-(p-benzyldiazonium)
      diethylenetriaminepentaacetic acid (aDTPA). After injection in nude mice bearing
      HuP-T4 xenografts, the biodistribution of 111In- and 125I-labeled MoAb 17-1A was
      examined at various time points. RESULTS: Positive staining of MoAb 17-1A was
      noted for HuP-T4 cells. A statistically significant (P < 0.01) greater tumor
      uptake was observed at 3 days after intravenous injection of 125I-labeled MoAb 17
      1A when compared with 125I-labeled nonspecific immunoglobulin G. 125I- and 111In
      labeled MoAb 17-1A was concentrated in HuP-T4 carcinoma 1.9-4.8 times higher than
      in the spleen, heart, liver, and pancreas. CONCLUSIONS: MoAb 17-1A was found to
      bind selectively to human pancreatic carcinoma HuP-T4. Tumor exhibited higher
      uptake of radiolabeled MoAb 17-1A compared with adjacent normal tissues. These
      results suggest that MoAb 17-1A may be applicable to the radioimmunodetection and
      radioimmunotherapy of pancreatic adenocarcinomas.

PMID- 8306264
TI  - Radioiodination of monoclonal antibodies D612 and 17-1A with 3
      iodophenylisothiocyanate and their biodistribution in tumor-bearing nude mice.
AB  - BACKGROUND: The development of a metabolically stable radioiodination reagent for
      coupling to monoclonal antibodies is a desirable goal. The radioiodination of
      monoclonal antibodies D612 and 17-1A reactive with human colon cancer with 3
      iodophenylisothiocyanate has been investigated. This new ligand, on coupling with
      monoclonal antibodies, should form a stable thiourea linkage via a reaction of
      the isothiocyanate moiety with the epsilon-amino group of lysine. METHODS: The
      starting material, 125I- or 131I-labeled 3-iodophenylisothiocyanate, was
      synthesized in good radiochemical yield with a purity of > 99% via a reaction of
      electrophilic radioiodine with 3-tri-n-butylstannylphenylisothiocyanate. The
      coupling of radiolabeled 3-iodophenylisothiocyanate with monoclonal antibodies
      D612 and 17-1A in different buffers was investigated. Biodistribution of these
      radioimmunoconjugates in athymic nude mice bearing colon cancer xenografts was
      studied. RESULTS: The results demonstrated that monoclonal antibodies labeled
      with 3-iodophenylisothiocyanate retained specific binding activity and showed
      significantly less thyroid uptake than did directly radioiodinated antibodies
      prepared by the iodogen method. Radioimaging and biodistribution studies
      demonstrated that uptake of these new radioimmunoconjugates in LS174T colon
      cancer xenografts was similar to that of directly radioiodinated antibodies,
      while their uptake in other normal tissues was similar to or lower than that of
      directly radioiodinated antibodies. CONCLUSIONS: These results demonstrate that
      high specific activity can be achieved and pure 3-iodophenylisothiocyanate can be
      derived easily from 3-tri-n-butyl-phenylisothiocyanate. Biodistribution and
      imaging studies revealed that monoclonal antibodies conjugated with 3
      iodophenylisothiocyanate are metabolically more stable in vivo in an animal model
      than directly radioiodinated antibodies, and that these new radioimmunoconjugates
      are localized selectively in tumors.

PMID- 8306265
TI  - Comparative biodistribution and radioimmunotherapy of monoclonal antibody RS7 and
      its F(ab')2 in nude mice bearing human tumor xenografts.
AB  - BACKGROUND: RS7 is a murine monoclonal antibody immunoglobulin G1 with pan
      carcinoma reactivity, which was raised against human squamous cell carcinoma of
      the lung. To optimize the use of monoclonal antibody RS7 as a carrier of
      radionuclides for tumor targeting and therapeutic applications, whole RS7
      immunoglobulin G and its F(ab')2 fragment were radiolabeled, and their
      biodistribution and effectiveness as radioimmunotherapeutic agents in nude mice
      bearing established human tumor xenografts were evaluated. The contributions of
      the tumor model, monoclonal antibody form (fragment vs. intact), radioisotope
      (131I, 111In, 90Y, and 188Re), and antigen target were evaluated. METHODS:
      Cumulative absorbed radiation doses were calculated from biodistribution data,
      and doses were normalized to blood to estimate expected relative toxicities. Two
      tumor models expressing different levels of RS7-antigen were studied: ME180, a
      cervical carcinoma cell line, and Calu-3, an adenocarcinoma of the lung cell
      line. In addition, the therapeutic effectiveness of 131I-RS7-F(ab')2 was compared
      to that of 131I-RS7-IgG. RESULTS AND CONCLUSIONS: Doses delivered to tumor
      (normalized to blood) calculated for 131I-RS7-F(ab')2 and 90Y-RS7-IgG were 4.7
      times and 1.8 times greater, respectively, than 131I-RS7-IgG, and therefore would
      be expected to yield greater therapeutic efficacy when equitoxic doses are
      administered. This expectation was confirmed in the radioimmunotherapy study with
      131I-RS7-F(ab')2. At equivalent absorbed dose to tumor, 131I-RS7-F(ab')2 was
      found to effect a slightly longer suppression of tumor growth than the intact
      131I-RS7 IgG, and a 50% dose escalation yielded tumor regression for a prolonged
      period with the fragment, whereas a similar 50% dose escalation with 131I-RS7-IgG
      could not be tolerated.

PMID- 8306266
TI  - Effect of seven new vasoactive immunoconjugates on the enhancement of monoclonal
      antibody uptake in tumors.
AB  - BACKGROUND: To enhance monoclonal antibody uptake in tumors, seven novel
      vasoactive immunoconjugates were developed that selectively alter the vascular
      permeability and/or blood volume of tumors in vivo. These immunoconjugates,
      composed of IL-1 beta, IL-2, TNF-alpha, physalaemin, leukotriene B4, histamine,
      and bradykinin chemically linked to TNT-1, a murine monoclonal antibody that
      binds necrotic regions in tumors, have been tested for their effects on antibody
      uptake in vivo. METHODS: Groups of four mice, each bearing the ME-180 human
      cervical carcinoma, were pretreated either 3 or 24 hours before the
      administration of I-125 labeled TNT-1 F(ab')2 fragment. Three-day biodistribution
      studies then were performed to determine the amount of radiolabeled antibody in
      the tumors and normal organs of the mice. In addition, mechanism of action
      studies were performed to determine if the vasoactive immunoconjugate affected
      the vascular permeability or blood volume of the tumor vessels. RESULTS: TNT-1/IL
      2 gave the highest percent injected dose/g in tumor (4.80), compared with TNT
      1/TNF (4.00), TNT-1/IL-1 (3.83), TNT-1/leukotriene-B4 (2.84), TNT-1/histamine
      (2.80), TNT-1/physalaemin (2.19), TNT-1/bradykinin (1.57), or TNT-1 alone (1.28).
      All of these immunoconjugates showed specific enhancement of monoclonal antibody
      uptake in tumor with no changes seen in normal tissues. Quantitative studies that
      demonstrated the mechanism of action of these immunoconjugates showed that TNT
      1/IL-2 and TNT-1/histamine produced a marked change in the vasopermeability of
      tumor vessels but had no effect on tumor blood volume. In contrast, TNT-1/IL-1
      and TNT-1/TNF produced a combination of effects, and TNT-1/leukotriene B4, TNT
      1/bradykinin, and TNT-1/physalaemin affected only tumor blood volume.
      CONCLUSIONS: These studies indicate that pretreatment with vasoactive
      immunoconjugates may improve monoclonal antibody uptake in tumors significantly
      and thereby increase the therapeutic index of monoclonal antibody-directed
      immunotherapy.

PMID- 8306267
TI  - Overview of clinical radioimmunodetection of human tumors.
AB  - The role of radioimmunodetection in the detection of cancer has been established
      through the development of high affinity immunoconjugates and recent improvements
      in radiochemistry. Advances in imaging techniques, particularly single-photon
      emission computed tomography and image registration, also have dramatically
      improved the sensitivity and accuracy of tumor detection. Molecular engineering
      of immune constructs provides promise of enhanced tumor localization properties
      and reduced immunogenicity, allowing repeated studies to be performed. The role
      of radioimmunodetection in the evaluation of cancer patients will increase in
      importance in the future.

PMID- 8306269
TI  - Comparison of radioimmunodetection with other imaging methods in evaluating local
      relapses of colorectal carcinoma.
AB  - BACKGROUND: The prognosis for colorectal cancer patients is related closely to
      the extent of tumor at the time of diagnosis, and early detection of metastatic
      or recurrent disease is an important prerequisite for successful treatment.
      Radioimmunodetection is a relatively new technique to image colorectal cancer
      using radiolabelled monoclonal antibodies (MoAb). The goal of this study was to
      evaluate the clinical use of radioimmunodetection with the anti-carcinoembryonic
      antigen MoAb FO23C5, radiolabelled with 131I, in patients submitted to surgery
      for colorectal cancer and with suspected local recurrences. The results of
      radioimmunodetection were compared with those of computed tomography,
      ultrasonography, magnetic resonance imaging, and other diagnostic techniques
      (gastrointestinal x-ray, endoscopy, and, in selected cases, a surgical second
      look). METHODS: Fifty-nine patients with a rise in carcinoembryonic antigen serum
      levels or a clinical suspicion of recurrences entered the study. Scintigraphy was
      performed at multiple interval times (4-100 hours) after an intravenous injection
      of radiolabelled FO23C5 F(ab')2 fragments. RESULTS: The cumulative results showed
      the high sensitivity (89%), specificity (78%), and accuracy (86%) of
      radioimmunodetection. Of the radiologic methods, only magnetic resonance imaging
      had the same accuracy (86%), with lower specificity (64%) and higher sensitivity
      (93%). Computed tomographic scan and ultrasonography displayed the poorest
      accuracy (68% and 47%, respectively). CONCLUSIONS: Radioimmunodetection is an
      important imaging technique that can be used in clinical practice for the follow
      up of the patient with colorectal carcinoma.

PMID- 8306268
TI  - Radioimmunodetection of colorectal carcinoma using technetium-99m-labeled Fab'
      fragments of the IMMU-4 anti-carcinoembryonic antigen monoclonal antibody.
AB  - BACKGROUND: Radioimmunodetection of cancer using monoclonal antibody fragments
      offers certain potential advantages over that with whole monoclonal antibodies,
      including the ability to image early (i.e., to provide images at an early time
      after injection of the radioantibody) while minimizing the incidence of human
      anti-mouse antibody response. This paper reports a prospective trial comparing
      radioimmunodetection with IMMU-4 (a murine anti-CEA monoclonal antibody) 99mTc
      labeled Fab' fragments to conventional imaging in 35 colorectal cancer patients.
      METHODS: All patients were investigated by conventional diagnostic methods (CDM)
      within 4 weeks of radioimmunodetection. Surgical corroboration of findings was
      obtained in 26 patients (15 with evidence of disease on CDM [CDM+] and 11 with
      abnormal serum CEA [CDM-] as the only evidence for recurrence). After 1 mg IMMU-4
      99mTc-Fab' was injected (19.3 mCi on average), patients underwent planar/SPECT
      radioimmunodetection 2-5 hours later and planar radioimmunodetection 18-24 hours
      later. Three patients underwent a second radioimmunodetection study 16, 20 and 23
      months after the first. RESULTS: Radioimmunodetection was superior to CDM,
      accurately predicting disease distribution in six nonsurgical and ten CDM+
      surgical patients, and was complementary to computed tomography in two
      nonsurgical and two CDM+ surgical patients. Radioimmunodetection would have
      directed or changed management decisions in 6 of the 15 (40%) CDM+ surgical
      patients. Radioimmunodetection correctly identified all recurrent tumor in 8 of
      11 CDM- surgical patients and was negative in one patient with cirrhosis and no
      recurrence, representing a potential clinical benefit of 82%. Analyzed on a
      regional basis, radioimmunodetection was found to be superior to CDM in
      extrahepatic abdomen and pelvis imaging and was complementary to (although not as
      accurate as) CDM in the liver. Human anti-mouse antibody did not develop in any
      of the patients, including three who were injected twice. CONCLUSIONS: IMMU-4
      99mTc-Fab' radioimmunodetection shows promise as a clinically useful diagnostic
      tool in patients with colorectal cancer, detecting disease often missed by
      conventional imaging. IMMU-4 99mTc-Fab' may prove useful for serial
      radioimmunodetection studies, because human anti-mouse antibody response does not
      appear to be a problem with this radioimmunoconjugate. It also has the advantage
      of permitting same-day imaging.

PMID- 8306270
TI  - Comparative tumor localization of whole immunoglobulin G anticarcinoembryonic
      antigen monoclonal antibodies IMMU-4 and IMMU-4 F(ab')2 in colorectal cancer
      patients.
AB  - BACKGROUND: Previous studies in the literature have suggested that radiolabeled
      F(ab')2 fragments might be superior to whole immunoglobulin G (IgG) for imaging
      and therapy of cancer because of their greater penetration in tumors. To test
      this hypothesis, the authors compared tumor and normal tissue uptake along with
      plasma clearance of 125I-labeled monoclonal antibody (MoAb) IMMU-4 whole IgG with
      its 131I-labeled F(ab')2 fragment. METHODS: Five patients with either liver
      metastases from colorectal cancer (n = 4) or intact primary tumors (n = 1)
      received a combination of 125I-IMMU-4 IgG (2 mCi/1 mg) plus 131I-IMMU-4 F(ab')2
      (10 mCi/1 mg) as a single 1-hour intravenous infusion on day 1. Serial blood
      samples were taken for up to 72 hours postinfusion to determine plasma clearance
      of each MoAb. On days 3-9, patients underwent exploratory laparotomy in which
      biopsies of tumor as well as normal tissues (liver, normal colon, lymph node, and
      blood) were obtained. Tissues were weighed and counted in a gamma counter, and
      the percent of injected dose per kilogram (%ID/kg) of each antibody, along with
      the radiolocalization index (RI), was computed (RI = %ID/kg tumor.%ID/kg normal
      tissue). RESULTS: Tumor uptake of both antibodies (2.3 +/- 0.53 %ID/kg) was
      significantly higher than that of normal tissues (0.56 +/- 0.12; P < 0.001),
      except for blood (2.8 +/- 0.83), resulting in an RI > or = 3. There were no
      significant differences in uptake (%ID/g) between F(ab')2 and IgG (F[ab']2 = 2.0
      +/- 0.57; IgG = 2.6 +/- 0.94). The mean +/- SD of plasma T1/2 was slightly
      shorter for F(ab')2 (28.8 +/- 7.2 hours) than for IgG (45.9 +/- 16.7; P = 0.08).
      CONCLUSION: In short, the biodistribution and pharmacokinetics of IMMU-4 F(ab')2
      were comparable to those of IMMU-4-IgG.

PMID- 8306271
TI  - Immunoscintigraphy of colon cancers with the human monoclonal antibody COU-1.
AB  - The human monoclonal immunoglobulin M (IgM) antibody, COU-1 is obtained from a
      human-human hybridoma, which is derived by fusion between a human B
      lymphoblastoid cell line and lymphocytes obtained from mesenteric lymph nodes
      from a patient with colorectal cancer. COU-1 recognizes a 43 kilodaltons
      intracellularly located cytokeratin-like protein, strongly expressed by
      adenocarcinoma tissue as compared to normal tissues. In tumor-bearing nude mice,
      antibody COU-1 labeled with 125I has been shown to accumulate in human colon
      cancer grafts when compared to human melanoma grafts and the normal mouse
      tissues. The observed accumulation was sufficient to be detected externally by
      immunoscintigraphy. Antigen-binding fragments of the antibody were also prepared
      and were shown to accumulate in colon cancer grafts. Improved tumor to normal
      tissue ratio was seen with the half-monomeric fragment, and the time required was
      reduced. In the clinic, five patients with suspected colorectal cancer were given
      2 mg of 131I-labeled COU-1. No adverse effects were detected in any of the
      patients. Planar images were obtained on days 1, 2, 3, 5, and 7 after
      administration. The best images were obtained on days 5 and 7. Tumors were
      localized by immunoscintigraphy in four of the patients. Of these patients,
      surgery revealed that three of them had primary colorectal cancers located in the
      cecum, the ascending colon, and the rectum, respectively, while one patient had a
      pancreatic cancer. The smallest lesion observed had a diameter of 3 cm. In one of
      the patients, otherwise undiagnosed multiple liver metastases were revealed by
      the immunoscintigraphy and confirmed at surgery. An x-ray of the colon performed
      on the fifth patient had shown a stricture in the descending colon suspected to
      be caused by cancer. The tumor scintigraphy showed no accumulation of the
      antibody. Surgery revealed that the stricture was caused by adherence and not
      cancer. These findings are encouraging for further studies of this human
      monoclonal antibody in cancer patients.

PMID- 8306272
TI  - Phase I clinical evaluation of a new murine monoclonal antibody (Mu-9) against
      colon-specific antigen-p for targeting gastrointestinal carcinomas.
AB  - BACKGROUND: Colon-specific antigen-p is a tumor-associated antigen present in
      approximately 60% of colorectal cancers. Preclinical studies have shown that the
      murine monoclonal antibody Mu-9 has excellent tumor-targeting abilities;
      therefore, clinical studies were initiated. METHODS: The immunoglobulin G and
      F(ab')2 were radiolabeled with 131I and administered to 13 and 12 patients,
      respectively, with advanced gastrointestinal cancer (colon, rectal, and
      pancreatic) for radioimmunodetection or radioimmunotherapy. RESULTS: Even in
      patients with highly elevated carcinoembryonic antigen levels, only one patient
      showed appreciable complexation of the labeled antibody, suggesting the epitope
      may not be highly expressed in the blood. Fifty percent of 131I-Mu-9
      immunoglobulin G was cleared from the blood within 41 +/- 13 hours, while it took
      only 19 +/- 8 hours for the same amount of 131I-F(ab')2 to be cleared from the
      blood. Lesion detection in the abdomen, liver, and pelvis was greater than 90%
      for either the immunoglobulin G or F(ab')2. The dose absorbed by the normal
      organs, except the kidneys, was two- to threefold less for the F(ab')2 than for
      the whole immunoglobulin G. The dose to the kidneys was similar for both forms of
      immunoglobulin. The average tumor dose for 131I-Mu-9 immunoglobulin G was 13.9 +/
      11.0 cGy/mCi, and for 131I-F(ab')2 was 4.9 +/- 2.9. Tumor/red marrow dose ratios
      for the whole immunoglobulin G were 4.3 +/- 3.0, compared to 3.3 +/- 1.9 for the
      F(ab')2, suggesting the therapeutic window for the two forms of immunoglobulin
      may be similar. Eight of nine patients given the whole immunoglobulin G developed
      highly elevated levels of human anti-mouse antibody, whereas lower values were
      observed in five of seven patients given the F(ab')2. CONCLUSIONS: These initial
      results support the need for further evaluation of Mu-9 immunoglobulin G and
      F(ab')2 for targeting gastrointestinal cancer for radioimmunotherapy.

PMID- 8306273
TI  - Detection of ovarian cancer by 198Au-labeled human monoclonal antibody.
AB  - BACKGROUND: There is no reliable method for the early diagnosis of ovarian
      cancer. Radiolabeled monoclonal antibodies have potential to assist in early
      diagnosis, but they are limited by problems that include antibody specificity,
      stability, and immunoreactivity, as well as patient reactions to the antibodies
      used. METHODS: Methods were developed to 198Au-label a human monoclonal antibody
      (TC5 antibody), developed against an ovarian cancer cell surface antigen. Antigen
      binding sites on the TC5 antibody were protected with sepharose 4B affinity
      chromatography before 198Au-labeling. The 198Au-labeled TC5 antibody was
      evaluated with biopsy specimens in a blind study. The immunoreactivity of
      radiolabeled TC5 antibody also was evaluated in slot-blot experiments with
      extracts of the biopsy specimens. RESULTS: The 198Au-labeled TC5 antibody had
      high binding reaction to all biopsy specimens (six of six) pathologically
      diagnosed as ovarian cancer (serous and endometrioid adenocarcinoma). The
      radiolabeled TC5 antibody did not bind to any normal (non-neoplastic) specimens
      (zero in ten), with one exception. One "normal" ovary specimen had high binding
      of radiolabeled TC5 antibody, and metastatic ovarian cancer was diagnosed 4
      months later. The TC5 antibody labeled with 198Au, without protecting antigen
      binding sites, did not bind to any biopsy specimens. CONCLUSIONS: The affinity
      labeling method was necessary to protect antigen-binding sites and preserve the
      immunoreactivity of the TC5 antibody. The 198Au-labeling method may be an ideal
      technique to evaluate monoclonal antibodies in vitro. The TC5 antibody had high
      sensitivity and specificity for detecting ovarian cancer.

PMID- 8306274
TI  - Indium-111-labeled anti-EGFr-425 scintigraphy in the detection of malignant
      gliomas.
AB  - BACKGROUND: The monoclonal antibody anti-epidermal growth factor receptor (EGFr)
      antibody-425, against the epidermal growth factor receptor, has the potential to
      bind specifically to gliomas and not normal brain tissue. A prospective study was
      conducted (1986-1988) to evaluate the use of Indium-111 (111In)-labeled anti-EGFr
      425 in the localization of gliomas before radioimmunotherapy with Iodine-125
      (125I)-labeled anti-EGFr-425. METHODS: Twenty-eight patients with intracranial
      neoplasms were injected intravenously with an average dose of 2.2 mCi 111In
      labeled anti-EGFr-425. Planar and single-photon emission computed tomography
      scans were performed after 48 and 72 hours. Control studies also were performed
      in two cases with 111In-labeled Co 17-1A (an antibody to colorectal cancer) and
      in one case with unlabeled 111In chloride. RESULTS: The immunoscintigraphic
      findings were generally in good agreement with computerized tomographic findings.
      The definitive diagnosis was established by biopsy findings: 23 gliomas (1 Grade
      I, 5 Grade II, 6 Grade III, and 11 Grade IV), 1 meningioma, and 4 metastatic
      lesions. The localization of gliomas with 111In-labeled anti-EGF-425 had a
      sensitivity of 0.96, a specificity of 0.60 and an accuracy of 0.90. CONCLUSION:
      Immunoscintigraphy with 111-In labeled anti-EGFr-425 can be useful in the
      management of malignant gliomas, especially before radioimmunotherapy with 125I
      labeled anti-EGFr-425.

PMID- 8306275
TI  - Radioimmunodetection of non-small cell lung cancer using technetium-99m
      anticarcinoembryonic antigen IMMU-4 Fab' fragment. Preliminary results.
AB  - BACKGROUND: Although computed tomography and magnetic resonance imaging have
      improved the staging and evaluation of non-small cell lung cancer (NSCLC),
      mediastinal staging lacks adequate specificity and sensitivity.
      Radioimmunodetection may augment computed tomography and magnetic resonance
      imaging. The authors evaluated the ability of the technetium 99m
      anticarcinoembryonic antigen IMMU-4 Fab' fragment to localize NSCLC in vivo,
      measured its pharmacokinetics, and estimated its radiation dose. METHODS:
      Seventeen patients with carcinoembryonic antigen-positive NSCLC received 16-30
      mCi of technetium 99m IMMU-4 Fab'. Planar imaging was performed at 1-7 hours and
      20-24 hours. Single-photon emission computed tomography (SPECT) was performed
      within 8 hours after injection. In 10 patients, blood sampling, urine collection,
      and quantitative imaging were performed to determine blood and urine
      pharmacokinetics and radiation dose estimates. Human anti-mouse antibody response
      was measured for as long as 3 months after administration. RESULTS: Planar and/or
      SPECT imaging detected 72% of 32 known lesions. SPECT was more sensitive than
      planar imaging. T1/2 alpha averaged 0.18 +/- 0.33 hours; T1/2 beta averaged 8.02
      +/- 5.53 hours. The mean concentration versus time value was 1.11 +/- 0.56 mg.h.
      The average whole body dose estimated for administration of 30 mCi was 0.45 +/-
      0.08 rads. No human anti-mouse antibody responses were detected. CONCLUSION: The
      tumor detection rate was high, but the persistent blood pool at < 8 hours
      complicated image interpretation. An intermediate imaging time point (12-16
      hours) might be preferable. SPECT is an important adjunct to imaging with this
      radioimmunoconjugate. The acceptable dosimetry estimated for 30 mCi Technetium
      99m IMMU-4 Fab' and the lack of human anti-mouse antibody responses suggest this
      is a promising localizing tool for NSCLC:

PMID- 8306276
TI  - Initial clinical results with technetium-99m-labeled LL2 monoclonal antibody
      fragment in the radioimmunodetection of B-cell lymphomas.
AB  - BACKGROUND: Various monoclonal antibodies (MoAb) labeled with Iodine-131 or
      Indium-111 (In-111) have been investigated for radioimmunodetection of Hodgkin's
      and non-Hodgkin's lymphomas. Successful radioimmunotherapy also has been
      reported. The purpose of this pilot study was to stage non-Hodgkin's B-cell
      lymphomas (NHL) using whole body scintigraphy with technetium-99m (Tc-99m)
      labeled murine monoclonal antibody LL2 (EPB-2) Fab' (Immunomedics, Morris Plains,
      NJ). Others have shown this MoAb to have specific binding to B-cell lymphomas by
      flow cytometry and immunofluorescence. Initial clinical studies by others have
      demonstrated targeting of NHL with the Tc-99m-labeled LL2-Fab'. METHODS: One
      milligram of the antibody was injected intravenously after being radiolabeled
      with 30 mCi Tc-99m. Fifteen patients with high (n = 6), low (n = 2), and
      intermediate (n = 7) grade NHL were studied. No adverse effects were noted.
      Planar whole body imaging and single-photon emission computed tomography were
      performed at 2-6 h and 20-24 h postinjection. Human anti-mouse antibody levels
      were determined before injection and at 2 and 6 weeks. RESULTS: In 4 of 15
      patients (27%), the disease stage was altered in response to the scintigraphic
      findings. The physiologic biodistribution of the antibody demonstrated splenic
      uptake caused by antibody targeting of the white pulp and of normal B-cells, and
      renal uptake caused by urinary excretion. Lymph node and bone marrow involvement
      of known tumor sites were clearly seen. A number of previously unknown tumor
      sites were revealed by LL2-radioimmunodetection despite normal morphologic
      imaging results. Long-term follow-up of these patients is required to verify
      these findings. No human anti-mouse antibody elevations or adverse reactions were
      found in the patients studied. CONCLUSION: These preliminary data suggest that Tc
      99m-labeled LL2 Fab' yields useful clinical results, especially for the staging
      of patients with NHL before initial therapy or for the detection of early disease
      recurrence.

PMID- 8306277
TI  - Immunoscintigraphy in cancer care.
AB  - Despite numerous publications on the ability of immunoscintigraphy to detect
      recurrent gastrointestinal and ovarian tumors much earlier than other diagnostic
      methods currently used in the postoperative follow-up, this method has still not
      received the clinical recognition it deserves. This is due to multiple factors,
      but mostly to the lack of well designed multicenter trials intended to assess the
      large scale efficacy of the method. The cost-benefit approach might be helpful in
      designing such studies.

PMID- 8306278
TI  - Radiation dosimetry for radioimmunotherapy. An overview of current capabilities
      and limitations.
AB  - BACKGROUND. The two major uncertainties associated with absorbed dose
      calculations involve: (1) measurement errors from assessment of radioactivity in
      specific organs and tissues by direct counting; and (2) application of standard
      anthropomorphic and biokinetic models for dose assessment. Uncertainties in
      direct counting result from the inherent difficulty of measuring radioactivity
      inside the body. Although the system recommended by the Medical Internal
      Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine provides a
      general framework and conceptual basis for the dosimetry of administered
      radiopharmaceuticals, it does not provide complete methods for assessing some of
      the more important quantities of interest in radioimmunotherapy, such as dose to
      tumors and descriptions of spatial dose distributions within tissues. Current
      MIRD anthropomorphic models are only crude representations of the human body.
      Generalized biokinetic models used in the MIRD system may vary considerably from
      the actual biokinetics of radiolabeled compounds in the body. This review
      describes limitations of the present MIRD system for radioimmunotherapy; they
      include assumptions used in treatment planning and the lack of specific methods
      for tumor dosimetry, multi-cellular dosimetry, microdosimetry, small animal
      dosimetry, and uncertainty analysis. CONCLUSIONS. Treatment planning for
      radioimmunotherapy requires patient-specific organ models and customized
      biokinetic parameters. Improvements are also needed in marrow dosimetry to
      account for the amount and distribution of red marrow relative to that found in
      adjacent source regions, skeletal structures, and circulating blood. Simplified
      assumptions with regard to the locally absorbed fraction of beta-particle energy
      in tissues adjacent to source regions should not be used when depth-dose profiles
      are needed; for example, radiation absorbed doses to intestinal walls should be
      calculated over the entire mass of tissue or described by absorbed-dose
      distributions. Additional research is needed to develop improved measurement
      techniques and computational methods to assess more accurately internal dose
      distributions within tumors and normal tissues.

PMID- 8306279
TI  - Three-dimensional reconstruction of monoclonal antibody uptake in tumor and
      calculation of beta dose-rate nonuniformity.
AB  - BACKGROUND: The measurement of the heterogeneity of radiolabeled monoclonal
      antibody uptake in tumor has an essential role in the calculation and
      interpretation of the absorbed dose of radiation. Large data arrays and long
      calculation times have been limiting factors in the calculation of three
      dimensional dose-rate distributions used to study the relationship between uptake
      heterogeneity and dose. METHODS: Serial autoradiographs of tumor sections were
      digitized with approximately 100 microns resolution using a laser densitometer.
      The section images were aligned to form a registered tumor-image data set. The
      image data were corrected for film response versus activity density to create a
      three dimensional activity density distribution using features of a three
      dimensional radiotherapy treatment planning system. Dose-rate distributions were
      formed by convolution with a beta dose kernel using fast Fourier transforms.
      RESULTS: Differential dose-rate-volume histograms (derived from the dose-rate
      distribution) were created to summarize the dose-rate nonuniformity throughout
      the tumor volume. Effects of section sampling interval, interpolation methods
      between section planes, and calculation resolution on the dose-rate-volume
      histograms were illustrated. CONCLUSIONS: The several orders of magnitude
      improvement in calculational speed provided by the fast Fourier transform
      technique allowed an investigation of the effects of the calculational
      parameters. This investigation enabled tuning of both data acquisition and dose
      computation. These studies can lead to further enhancements in the calculational
      efficiency of three-dimensional dose-rate distributions. These improvements will
      allow the study of summing techniques to yield average total dose distributions.

PMID- 8306280
TI  - Organ modeling in the quantitation of planar images for distribution studies.
AB  - BACKGROUND: The advantage of whole-body imaging for distribution studies is that
      it accounts for all activities. The problem, however, is that the classic
      approach to determining distribution from planar images does not accommodate
      overlapping structures. That approach assumes implicitly that the sampling region
      is a prismoid whose cross-section, parallel to the detector plane, is defined by
      a region of interest and whose sides are orthogonal to the detector plane.
      METHODS: In the proposed organ-model approach, the region of interest is assumed
      explicitly to be the projected shadow of an organ or structure, whose general
      shape is known from anatomic generality, and whose size or specific shape
      variation is defined by the shadow or region of interest. If "j" is a pixel in
      the organ shadow "i", a fraction "Vij" of the volume of organ "i" is assumed to
      project orthogonally in "j". More than one organ shadow can overlap, in which
      case the volumes projecting in "j" are the sum of "Vij" over "i". The activity
      "Aj" (count rate density) in any location "j" is defined by the linear
      combination of volumes "Vij" and concentrations "Ci". For all the pixels in the
      image, this defines an overdetermined set of linear equations that can be solved
      by matrix inversion for "Ci", the organ concentrations. RESULTS: The organ-model
      method was tested on simulated and phantom data. It proved, on serial and repeat
      processing, to be robust (not subject to large errors due to small variations) if
      the images had sufficient contrast. This method was found to be superior to the
      classic approach in evaluating the same data, because in the classic approach,
      the border regions are too heavily weighted, and therefore, the size of the
      sampling region is critical. Furthermore, the expression of the results in
      concentrations is more relevant to dosimetry, the derivation of which is based on
      cumulative concentrations. CONCLUSION: Modeling organ shadows is a viable
      improvement on the use of regions of interest to quantify tracer distribution in
      planar imaging.

PMID- 8306281
TI  - A new fiducial alignment system to overlay abdominal computed tomography or
      magnetic resonance anatomical images with radiolabeled antibody single-photon
      emission computed tomographic scans.
AB  - BACKGROUND: The use of computed tomography (CT) or magnetic resonance (MR) to
      overlay or register uptake patterns displayed by single-photon emission computed
      tomography (SPECT) with specific underlying anatomy has the potential to improve
      image interpretation and decrease diagnostic reading errors. The authors have
      developed a method that will allow the selection of a region of interest on MR or
      CT images that correlates with SPECT antibody images from the same patient. This
      method was validated first in phantom studies and subsequently was used on three
      patients with suspected colorectal carcinoma. METHODS: Two patients were injected
      with the technetium-99m-labeled 88BV59 immunoglobulin G human antibody, and the
      third patient was injected with the iodine-131-labeled 16.88 immunoglobulin M
      human antibody. CT or MR scans were obtained before antibody infusion, and
      subsequent SPECT scans were obtained on the first or fourth day after infusion. A
      customized body cast with landmarks was used for each patient during the CT, MR,
      and SPECT scans to match slice positions for all scanning modalities.
      Corresponding fiducial landmarks were identified on axial images. A computer
      graphics program was written to match and overlay corresponding landmarks for
      each imaging modality. The image registration accuracy was measured by comparing
      fiducial marker separations (center to center) on the registered scans. This
      separation uncertainty was 1-2 mm for CT-MR and 3-4 mm for CT-SPECT phantom
      studies. RESULTS: For patient studies, the fiducial alignment uncertainty was 3-4
      mm for axial CT-SPECT and MR-SPECT images, and 6-8 mm for sagittal CT-SPECT and
      MR-SPECT images. The accuracy of the anatomic alignment of the patient and image
      registration system was +/- 1 cm in the medial-lateral axis and +/- 2 cm in the
      cranial-caudal direction. CONCLUSIONS: This type of image analysis may resolve
      uncertainties with the anatomic correlation of SPECT images that otherwise may be
      regarded as questionable when SPECT is used alone for radioimmunodiagnosis.

PMID- 8306282
TI  - Tumor activity confirmation and isodose curve display for patients receiving
      iodine-131-labeled 16.88 human monoclonal antibody.
AB  - A study was performed to correlate activity quantitation derived from external
      imaging with surgical tumor specimens in patients who received radiolabeled
      monoclonal antibody. Patients were given I-131 labeled 16.88 human antibody and
      scanned 3-5 times by planar and/or single photon emission computed tomography
      imaging methods to acquire time-dependent activity data in tumor and normal
      tissues. A method also was developed to assess the heterogeneous activity
      distributions in tumor samples. Postsurgical tumor and normal tissue samples were
      subdivided into volume elements (voxels) of 0.5 cm x 0.5 cm x 0.05 cm thick,
      which were used to verify the activity quantitation computed by the conjugate
      view method and to appraise the heterogeneity of radiolabeled antibody uptake.
      Through the use of the measured voxel activities, along with the time-dependent
      activity curves available for the entire tumor specimen derived from imaging, the
      cumulated activity and absorbed dose for each voxel were uniquely determined. The
      calculated total absorbed dose values were color-coded as isodose curves and
      overlaid on a correlated computed tomographic image. In two patients, activity
      quantitation derived from external imaging correlated with surgical tumor
      resection specimens within +/- 11%. The tumor-absorbed dose heterogeneity ratio
      was found to be as high as 10:1, with an average tumor to whole body absorbed
      dose ratio of 4:1. The mapping of activity with a histologic overlay showed a
      good correlation among activity uptake, the presence of tumor, and antigen
      expression on a microscopic scale. The resultant isodose curves overlaid on
      correlative computed tomographic scans represent the first images obtained with
      actual radiolabeled antibody biodistribution data in patients.

PMID- 8306283
TI  - Use of bremsstrahlung radiation to monitor Y-90 tumor and whole body activities
      during experimental radioimmunotherapy in mice.
AB  - BACKGROUND: Large differences in uptake between tumors, even for the same size,
      frequently observed in clinical and experimental radioimmunotherapy (RAIT), make
      monitoring of uptake in individual tumors imperative in comparing protocols. 90Y,
      widely-used for RAIT, emits no gamma radiation and absorption of the beta
      particle in tissue makes its detection unsuitable for in vivo monitoring. We
      tested whether bremsstrahlung radiation, produced when betas are decelerated by
      nuclei, could be used to monitor tumor uptake. METHODS: Subcutaneous human LS174T
      colon carcinoma tumors were grown in the upper thigh of nude mice and labeled
      antibody injected intracardially. With the tumor placed in the 2 cm-diameter
      aperture in a lead collimator, photons with energies from 100 to 200 keV
      transmitted through plastic, which absorbed the beta particles, were counted to
      maximize shielding from the rest of the body. The contribution of the normal
      tissues was subtracted by counting the non-tumor-bearing leg in the same
      position. Excretion was calculated from whole body activity determined by
      removing the collimator, placing the mouse in a syringe surrounded by tissue
      equivalent material 10 cm from the detector, and counting photons between 200 and
      740 keV to minimize the effect of tissue attenuation. RESULTS: For tumors larger
      than 0.14 gm, a good correlation was obtained between the in vivo bremsstrahlung
      measurements and the measurements on excised tumors in a calibrated well counter.
      Similar excretion rates observed in all the animals suggested that the whole body
      counting was accurate. CONCLUSIONS: Bremstrahlung detection appears feasible and
      reliable for monitoring both tumor and whole body activities.

PMID- 8306284
TI  - A mouse model for calculating cross-organ beta doses from yttrium-90-labeled
      immunoconjugates.
AB  - BACKGROUND: The organs of laboratory mice used in radioimmunotherapy experiments
      are relatively small compared to the ranges of high-energy yttrium-90 (Y-90) beta
      particles. Current Medical Internal Radiation Dose (MIRD) dosimetry methods do
      not account for beta energy that escapes an organ. A dosimetry model was
      developed to provide more realistic dose estimates for organs in mice who
      received Y-90-labeled antibodies by accounting for physical and geometric
      factors, loss of beta dose due to small organ sizes, and cross-organ doses.
      METHODS: The dimensions, masses, surface areas, and overlapping areas of
      different organs of 10 athymic nude mice, each weighing approximately 25 g, were
      measured to form a realistic geometric model. Major organs in this model include
      the liver, spleen, kidneys, lungs, heart, stomach, small intestine, large
      intestine, thyroid, pancreas, bone, marrow, and carcass. A subcutaneous tumor
      mass also was included in the model. By accounting for small organ absorbed
      fractions and cross-organ beta doses, the MIRD methodology was extended from
      humans to mice for beta dose calculations. RESULTS: Absorbed fractions of beta
      energy were calculated using the Berger's point kernels and the electron
      transport code EGS4. Except for the tumor and carcass, the self-organ absorbed
      fractions ranged from 15% to 20% in smaller organs (the marrow and thyroid) to
      65%-70% in larger organs (the liver and small intestine). Cross-organ absorbed
      fractions also were calculated from estimates of the overlapping surface areas
      between organs. CONCLUSION: The mathematic mouse model presented here provides
      more realistic organ dosimetry of radiolabeled monoclonal antibodies in the nude
      mouse, which should, in turn, contribute to a better understanding of the
      correlation of biodistribution study results and organ-tumor toxicity
      information.

PMID- 8306285
TI  - Application of the cross-organ beta dose method for tissue dosimetry in tumor
      bearing mice treated with a 90Y-labeled immunoconjugate.
AB  - BACKGROUND: Radioimmunotherapy of nude mice bearing human tumor xenografts using
      90Y-labeled monoclonal antibodies has resulted in slower tumor growth, decreased
      tumor burden, and increased survival times. Dosimetry estimates in the murine
      model usually were based on biodistribution data and standard Medical Internal
      Radiation Dose approaches. A new dosimetric model for the mouse that takes into
      consideration the small dimensions, mass, and proximity of murine organs has been
      developed based on self-organ absorbed and cross-organ doses. METHODS: Nude mice
      bearing carcinoembryonic antigen-expressing WiDr human colon cancer xenografts
      were injected with 240 microCi 90Y-anti-carcinoembryonic-antigen monoclonal
      antibodies and then killed at 12, 24, 72, 120, and 168 hours. Tumors and major
      organs were removed, weighed, and counted on a gamma counter. Using the resulting
      biodistribution data, the radiation doses to tumor and normal organs were
      calculated using the new dosimetric model for the mouse. RESULTS: Three organs
      (the liver, kidneys, and large bowel) directly received > 50% of the total
      absorbed beta dose from radioactivity. Lungs, stomach, and marrow received the
      highest percentage (70-75%) of the total absorbed dose from adjacent organs.
      Tumor absorbed dose, estimated with the new dosimetric model, was three times
      less than that obtained with a MIRD-style calculation without correction for self
      absorbed and cross-organ doses. CONCLUSIONS: The new dosimetric model, which
      accounts more accurately for self-organ absorbed and cross-organ beta dose
      fraction, allows the calculation of tumor and organ doses in the murine model.
      Accurate estimation of radiation doses to tumor and critical organs, such as the
      marrow, spleen and kidneys, is important in determining the efficacy and toxicity
      of radioimmunotherapy regimens in animals and in subsequent human applications.

PMID- 8306286
TI  - Radiobiologic studies of low-dose-rate 90Y-lymphoma therapy.
AB  - BACKGROUND: Radioimmunotherapy and other forms of biologically targeted
      radiopharmaceutic treatment appear to show unexpected efficacy in many patients
      with lymphoma, neuroblastoma, and several other types of nonepithelial
      malignancies. The radiobiologic mechanisms responsible for this high clinical
      radioresponsiveness are unclear, but must involve some sort of cytotoxic
      enhancement or sensitization to protracted courses of low-dose-rate radiation
      exposure. MATERIALS AND METHODS: A series of in vitro experiments was performed
      with malignant lymphoma cell lines exposed under various conditions to high-dose
      rate external beam radiotherapy or low-dose-rate 90Y radiation. Data were
      collected on cell cycle effects, DNA fragmentation, and modulation of
      cytotoxicity by caffeine and treatment sequence alterations. RESULTS: The data
      showed that some malignant lymphoma lines are highly sensitive to low-dose-rate
      radiation and that a portion of the cytotoxicity appears to be mediated by the
      induction of radiation-associated apoptosis (programmed cell death). Cell cycle
      effects of low-dose-rate radiation (such as G2M block) appear to be relatively
      minor in this experimental system. Agents that modulate apoptosis (such as the
      calcium-releasing agent caffeine) significantly enhance cell kill and DNA
      fragmentation after 90Y treatment. CONCLUSIONS: These results suggest that
      radiation-associated apoptosis may be important in the radiobiology of targeted
      radiopharmaceutical therapy.

PMID- 8306287
TI  - The impact of tumor cell proliferation in radioimmunotherapy.
AB  - BACKGROUND: In conventional radiotherapy, proliferation of tumor cells throughout
      treatment is believed to be an important cause of treatment failure. For
      radioimmunotherapy (RAIT), tumor cell proliferation will be a significant
      mechanism to consider when designing therapeutic strategies. METHODS: A
      mathematic model, based on the irradiation of a proliferating tumor cell
      population by an exponentially decaying dose-rate, was used to examine the
      effects of proliferation during RAIT. RESULTS: Proliferation can give rise to
      dose-rate effects in tumors that are distinct from those attributable to repair
      or recovery from radiation damage. An equation for the therapeutic efficiency of
      RAIT was generated. The analysis showed that RAIT will be less effective on
      rapidly proliferating tumor cell populations. High radioresistance causes a
      radiation dose to produce less tumor cell sterilization. In addition, for RAIT,
      the proportion of the dose that is "wasted" because of proliferation will be
      greater for radioresistant tumors. Therapeutically, higher initial dose-rates are
      more effective, meaning that, dose for dose, shorter decay half-lives will be
      better than longer ones. The analysis indicates that the therapeutic efficiency
      depends on tumor size and dosimetric heterogeneity and implies that
      micrometastases and "cold spots" in tumors could be major foci of recurrence.
      CONCLUSIONS: The results of this study support the use of RAIT as part of an
      integrated treatment regimen featuring local radiotherapy to bulk disease, and
      systemic treatment with total body irradiation plus bone marrow rescue and/or
      chemotherapy.

PMID- 8306288
TI  - Small animal imaging with pinhole single-photon emission computed tomography.
AB  - BACKGROUND: High resolution spatial details of the distribution of activity in
      three dimensions is required to evaluate the localization and dosimetric
      properties of radiolabelled monoclonal antibodies in tumors and normal tissues.
      Planar imaging of small animals with a resolution of 5-10 mm is usually the
      imaging modality of choice. The authors investigated high resolution single
      photon emission computed tomographic (SPECT) imaging, based on a rotating pinhole
      scintillation camera. Although the sensitivity of the pinhole collimator is low,
      several radionuclides offer suitable decay properties to perform pinhole SPECT,
      especially in conjunction with high activity levels used in radioimmunotherapy.
      METHODS: Transverse, sagittal, and coronal sections were reconstructed using a
      three-dimensional cone-beam algorithm, which is a generalization of the two
      dimensional fan-beam filtered backprojection algorithm. Before reconstruction,
      the pinhole projections were corrected for the decay of the radionuclide,
      geometric and intrinsic efficiency variations of the camera system, and center of
      rotation shift. RESULTS: The spatial resolution at 50 mm from the pinhole
      collimator with 3.3 mm aperture was 3.4 mm, and the sensitivity 7.2 c/s microCi
      for technetium-99m. With the 2 mm collimator the resolution was 2.2 mm, and the
      sensitivity was 2.6 c/s/microCi. To show the spatial resolution in vivo, a rat
      was injected with 185 MBq of technetium-99m-methylene diphosphonate or with 5 mCi
      technetium-99m-hexamethylpropylene amine oxime. The bone structures were well
      delineated in the methylene diphosphonate image, and in the hexamethylpropylene
      amine oxime image, the brain was nicely shown. For comparison a magnetic
      resonance image for the same section was done. CONCLUSIONS: High resolution SPECT
      imaging with the pinhole collimator provides mapping of the activity in three
      dimensions, needed for more detailed biodistribution data and to perform more
      accurate dosimetry.

PMID- 8306289
TI  - Parameters to consider for measurements of absorbed doses in vivo with mini
      thermoluminescent dosimeters.
AB  - BACKGROUND: For systemic radiation therapy, i.e., radioimmunotherapy, there is a
      demand for direct methods of measuring the absorbed dose in vivo. One such method
      is the use of mini-thermoluminescent dosimeters (TLDs). This paper reports an
      investigation of the sensitivity of tissue implanted mini-TLDs (calcium
      sulfate:Dy, 0.2 x 0.4 x 5.0 mm). METHODS: After being irradiated with cobalt-60,
      the mini-TLDs were left for as long as 9 days in air, gel, and muscle tissue.
      RESULTS: There was an extensive signal loss, which increased with time, except in
      air. After 9 days in gel or muscle tissue at room temperature, the signal was
      decreased to one third of its original value. The dosimeters needed to be kept in
      constant darkness. There was a strong pH dependence, with a loss of sensitivity
      of 63% at a pH below 5, which got smaller at higher pH values and reached 10% at
      pH = 10. CONCLUSIONS: When using mini-TLDs in vivo, one must calibrate the
      dosimeters in similar milieus, unless the position of the dosimeters in tissue
      after implantation can be monitored for temperature, pH, and liquid flow.

PMID- 8306290
TI  - Experimental radioimmunotherapy. A brief overview.
AB  - This overview highlights the use of experimental models in selecting monoclonal
      antibodies and radiolabels with promise for clinical radioimmunotherapy,
      discusses some of the experimental therapeutic approaches being studies in these
      models, and reviews some of the limitations of animal models caused by the
      allometric and other differences between man and mouse. These differences in
      scale must be considered when attempting to extrapolate animal radioimmunotherapy
      study data to human trials of radioimmunotherapy. With appropriate recognition of
      their limitations, experimental models of radioimmunotherapy have proven valuable
      and will continue to play a critical role as the place to first study innovations
      in radioimmunotherapy, before extension of the most promising reagents and
      treatment concepts into clinical therapeutic trials.

PMID- 8306291
TI  - Biodistribution and preclinical radioimmunotherapy studies using radiolanthanide
      labeled immunoconjugates.
AB  - Lutetium-177 (177Lu), samarium-153 (153Sm), and yttrium-90 (90Y) are members of
      the family of elements known as lanthanides or rare earths. Monoclonal antibody
      CC49, a murine immunoglobulin (Ig) G1, which is reactive with the tumor
      associated antigen TAG-72, previously has been shown to react with a wide range
      of human carcinomas. The authors review here the comparative biodistributions of
      CC49 IgG and F(ab')2 fragments labeled with 177Lu, 153Sm, and 90Y using the
      bifunctional chelating agent PA-DOTA. The authors also review the results of a
      biodistribution study comparing iodine-125-labeled and 177Lu-labeled CC49 sFv,
      and the use of 177Lu-CC+9 IgG in an experimental therapy model. Chelation and
      conjugations gave similar yields, and the labeled proteins showed similar
      retention of immunoreactivity regardless of the isotope used for both IgG and
      F(ab')2. Biodistribution data obtained in athymic mice bearing LS-174T human
      colon carcinoma xenografts likewise showed no differences among the three
      radioisotopes for both IgG and F(ab')2. Femur uptake of radioactivity was lower
      than previously reported for other radiolanthanide immunoconjugates. Different
      metabolic patterns were observed for radioiodinated versus radiometal-labeled
      sFv, particularly in the kidney, where localization of the latter was increased
      dramatically. 177Lu-CC49 was found to delay the growth of established LS-174T
      human colon carcinomas in athymic mice at a single dose of 50 microCi.
      Elimination of established tumors was demonstrated over the observation period
      (77 days) using single administrations of 200 or 350 microCi. Dose fractionation
      experiments revealed that the mice tolerated 750 microCi (3 x 250 microCi, given
      weekly), whereas > 50% of the mice died after receiving a single administration
      of approximately 500 microCi. In isotype-matched control experiments, a large
      differential in the therapeutic effects was observed between 177Lu-labeled
      control antibody and CC49.

PMID- 8306292
TI  - Sensitization of radiolabeled monoclonal antibody therapy using
      bromodeoxyuridine.
AB  - BACKGROUND: Although treatment with radiolabeled monoclonal antibodies (MoAb)
      against tumor-associated antigens offers the potential for targeted therapy, the
      efficacy of this approach is limited by the low dose-rate delivered. This could
      be overcome by increasing tumor sensitivity through the use of radiation
      sensitizers. METHODS AND RESULTS: In vitro studies using LS174T human colon
      cancer cells showed that exposure to 1 microM bromodeoxyuridine (BrdUrd), a
      thymidine-analog radiation sensitizer, at a plasma concentration easily
      achievable through systemic administration in both animals and patients,
      increased the cytotoxicity of continuous low dose-rate irradiation delivered by a
      cesium-137 irradiator (at 12 cGy/h which resembles the dose-rate delivered by
      radiolabeled MoAb therapy). It was found that 1 microM BrdUrd produced marked
      radiosensitization (enhancement ratio of 1.42 +/- 0.03) but did not affect cell
      cycle distribution. Systemic administration of BrdUrd in athymic nude mice
      bearing LS174T xenografts was performed using osmotic pumps. Animals tolerated
      infusions of 200 mg/kg/day BrdUrd for 4 days, which resulted in 8.4 +/- 0.8% of
      thymidine replacement by BrdUrd in tumors. However, bone marrow incorporation was
      15.8 +/- 1.1% under these conditions. To improve the ratio of incorporation in
      the tumor compared to that in the bone marrow, animals were given an infusion of
      BrdUrd and the pumps were removed. Incorporation of BrdUrd in the bone marrow and
      intestine decreased rapidly after the infusion was completed. In contrast, there
      was relatively little change in the incorporation into the tumor after an initial
      decrease. Based on these data, experiments were performed comparing the effects
      of 500 microCi iodine-131-labeled 17-1A MoAb alone to the same dose of iodine-131
      labeled 17-1A administered 1 day after discontinuation of the infusion of BrdUrd
      (200 mg/kg/day for 4 days). BrdUrd tended to increase the delay in tumor growth
      produced by iodine-131-labeled 17-1A administration. CONCLUSIONS:
      Radiosensitization by BrdUrd in vitro appears to be caused not by cell cycle
      effects but by increased radiation sensitivity. The in vivo data suggests that
      BrdUrd improved the efficacy (tumor growth inhibition) of radiolabeled MoAb.

PMID- 8306293
TI  - 3D display: a survey from theory to applications.
AB  - We survey some of the literature on three-dimensional medical imaging. We report
      both on technical developments and on medical applications, with a concentration
      on material that has been published within the years 1990-1992.

PMID- 8306294
TI  - A new method for representing the human anatomy.
AB  - In current practice, anatomical atlases are based on a collection of planar
      images presented in a book or, recently, stored on digital media. We present a
      new method for generating interactive true three-dimensional (3D) anatomical
      atlases based on a volume model derived from MRI and CT. The model has a two
      layer structure. The lower level is a volume model with a set of semantic
      attributes connected to each voxel. The semantic attributes are assigned by an
      anatomist using a volume editor. The upper level is a set of relations between
      these attributes. Interactive visualization tools such as multiple surface
      display, transparent rendering, and cutting are provided. It is shown that the
      combination of this data structure with advanced volume visualization tools
      provides the "look and feel" of real dissection. First tests show that the atlas
      system cannot only be used successfully for anatomy teaching, but also as a
      reference for radiologists or surgeons. As a replacement of classical atlases,
      however, the spatial resolution has still to be improved.

PMID- 8306295
TI  - 3D display of high resolution vertebral structure images.
AB  - A methodology for three-dimensional (3D) representation of vertebral trabecular
      structures was proposed. A set of X-ray CT images was obtained using a specific
      high resolution acquisition system. The images were then segmented in order to
      separate trabecular and cortical bone structures. Finally, the complex 3D
      surfaces were visualized using a volume rendering technique.

PMID- 8306296
TI  - Assessment and visualization of the curvature of the left ventricle from 3D
      medical images.
AB  - We address the problem of using curvature features to assess the three
      dimensional (3D) motion of the left ventricle. The adequacy of this approach
      depends on the actual characteristics of the curvature of the left ventricle and
      particularly on the spatial and temporal stability of these features. From
      experimental data, we compute the distribution of the Gaussian curvature over the
      surface of the left ventricle by using an iterative procedure. The results are
      visualized in 3D through a voxel-based surface rendering technique. We show that
      the Gaussian curvature remains stable along the cardiac cycle. This curvature
      feature could thus provide a reliable basis for further 3D motion analysis of the
      left ventricle.

PMID- 8306297
TI  - Rationale for, and recent progress in, 3D reconstruction of the heart and lungs.
AB  - Three-dimensional information of the structure and function of the heart and
      lungs is needed for several reasons including the following: (a) An apparent
      change in shape or location of the imaged ventricular wall may either be due to
      the heart moving through the imaged region, or because it truly represents that
      change in geometry, or a mixture of the two. In addition, as diseases of the
      heart and lungs are often heterogeneous in their spatial distribution, we expect
      the structural and functional consequences to also be heterogeneous in their
      spatial distribution; (b) Comparison of a selected anatomic feature (e.g., a
      coronary artery stenosis or pulmonary opacity) at long time intervals may make
      detection and/or quantitation of lesion progression questionable. The use of a 3D
      reconstruction to calculate a projection image with a reproducible angle of view
      is a particularly powerful consequence of 3D image reconstruction; (c) Use of
      image information from one imaging modality helps improve the quantitative
      characteristics of an image generated with another imaging modality; (d)
      Radiation treatment planning requires knowledge of the 3D distribution of
      radiation attenuation coefficients so that 3D distribution of the regional
      deposition of radiation energy can be quantitated; (e) Allows for indirect
      estimation of the physiological dimensions of one aspect of an organ so that the
      degree of disease of that part of the organ can be assessed.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8306298
TI  - Model based dynamic 3D reconstruction and display of the left ventricle from 2D
      cross-sectional echocardiograms.
AB  - In this paper we describe a technique for dynamic three-dimensional (3D)
      reconstruction of the left ventricle, using boundaries from multiple two
      dimensional (2D) echocardiographic views. We use a geometric model of the left
      ventricle and anatomical landmarks to relate the recorded views to positions
      within the model. The reconstruction is step-wise refined by replacing model data
      with recorded contour data.

PMID- 8306299
TI  - Cone-beam SPECT with a tilted detector.
AB  - In this article we report on the TOMOCONIC project for cerebral SPECT using cone
      beam collimators. First, we describe our experimental set-up. The cone-beam
      collimator improves both spatial resolution and sensitivity. We tilt the detector
      to center the focal point rotation plane on the region to reconstruct. Then, to
      minimize cone-beam artefacts, we use the Grangeat algorithm for image
      reconstruction. We describe here how it can be generated to this tilted
      acquisition geometry. Finally, we present our first experimental results and a
      comparison with parallel-beam SPECT. The improvement ratio on transverse spatial
      resolution is 1.5. We conclude with our first clinical images.

PMID- 8306300
TI  - Camera virtual equivalent model 0.01 pixel detectors.
AB  - In computer vision, a standard approach to eliminate spatial distortion is to use
      a calibrated grid. We developed an original method using such a grid to establish
      an equivalence between any camera with inherent technical limitations (optic,
      solid-state sensor, digitizer) and a perfect virtual pinhole camera model. This
      bijection based on interpolation concepts takes all the deformations generated by
      the optical and electronical equipment into account (distortion, decentration,
      scale, and affinity ratios) without the need for their explicit determination. We
      propose a detection method of this grid image by the use of grey levels
      approximation surfaces particularly adapted to this problem. We obtained a good
      precision on real grid images with modelization errors standard deviation of
      about 0.007 pixels with an off-the-shelf 512 x 512 camera using 256 grey levels.
      Three interpolation methods are compared: bilinear, cross-ratio in projective
      coordinates and bicubic splines. We conclude from this study that, in distorted
      images, the use of the bicubic splines interpolation method is a good
      improvement.

PMID- 8306301
TI  - Geometrical calibration of X-ray imaging chains for three-dimensional
      reconstruction.
AB  - Reconstructing a three-dimensional (3D) object from a set of its two-dimensional
      (2D) X-ray projections requires that the source position and image plane
      orientation in 3D space be obtained with high accuracy. We present a method for
      estimating the geometrical parameters of an X-ray imaging chain, based on the
      minimization of the reprojection mean quadratic error measured on reference
      points of a calibration phantom. This error is explicitly calculated with respect
      to the geometrical parameters of the conic projection, and a conjugate gradient
      technique is used for its minimization. By comparison to the classical
      unconstrained method, better results were obtained in simulation with our method,
      specially when only a few reference points are available. This method may be
      adapted to different X-ray systems and may also be extended to the estimation of
      the geometrical parameters of the imaging chain trajectory in the case of dynamic
      acquisitions.

PMID- 8306302
TI  - 3D reconstruction of gastric surface using endoscopic 3 source photometry.
AB  - Extraction and recognition of three-dimensional (3D) shape information of gastric
      surface become increasingly important in the field of gastric diagnosis. But
      there is no practical method that can extract the 3D shape information of gastric
      surface. For obtaining this 3D information, we developed a new photometric method
      that can be used in TV endoscope, and evaluated the proposed method theoretically
      and experimentally. As the results of simulation and experiment, it could be
      concluded that the proposed method is effective for 3D reconstruction of gastric
      surface.

PMID- 8306303
TI  - Image quality study in 3D X-ray angiography: a first approach using the
      experimental design strategy.
AB  - The visual detection of fine structures and the accuracy of the quantitation of
      geometric and densitometric features, are closely related to the quality of the
      images available in two-dimensional (2D) and three-dimensional (3D) X-ray
      angiography. In this context, we propose to analyze all the parameters
      influencing this accuracy using an experimental design strategy. Preliminary
      tests of this procedure, applied to 2D and 3D angiographic data obtained from a
      dedicated phantom, yield encouraging results. We show that the detection of small
      arteries in a 3D angiogram is more sensitive to the number of projections than to
      the X-ray dose.

PMID- 8306304
TI  - Time interpolation of angiograms toward stereoscopic display and reconstruction.
AB  - In the case of non simultaneous acquisitions of stereoscopic images, an object
      motion biases the 3D visualisation or reconstruction. We propose a method in
      order to find the interpolated image between two successive frames. It supposes
      that the motion locally corresponds to a translation. It works in the frequential
      domain and uses the phase information of the DFT. A special analysis of the phase
      component is made and allows to find the true interpolated phase. The application
      to stereoscopic angiographies illustrates the method and gives good results.

PMID- 8306305
TI  - Modeling the moving skeleton of walking subjects.
AB  - The proposed study consists in moving several bones such as pelvis, femur and
      tibia in conditions as similar as possible to those obtained in a walking
      subject, to evidence the functioning of this hip and knee joints. The analysis is
      performed during the stance phase when the joints are loaded. This study is the
      first phase of a research consisting in: (i) the visualization of the motion of
      joints in both normal and pathologic subjects; and (ii) the calculation in real
      time of articular loading caused by muscular forces when sustaining both the
      external and inertial loads. This research will provide the kinematic and dynamic
      boundary conditions applied to both a knee and a hip prosthesis of the patient in
      movement.

PMID- 8306306
TI  - Three-dimensional modeling of tree-like anatomical structures.
AB  - In this paper a method for creating geometrical models of tree-like anatomical
      structures is described. This method is basically interactive and thus it takes
      advantage of the user's expertise to define highly-structured models even when
      using nonhomogeneous data sets. First, tubular cavities are reconstructed
      sequentially; then, junctions between these cavities are provided in such a way
      that resulting models are continuously shaped (we characterize this property by
      the G1-continuity (i.e., a tangent plane can be defined at any point on the
      surface).

PMID- 8306307
TI  - 3D modeling of phased array generated ultrasounds in lossy media.
AB  - A general algorithm for three-dimensional (3D) modeling of acoustic fields
      generated by phased array transducers and propagating in uniformly lossy media is
      introduced and illustrated also with the help of specific examples. Applications
      of the method are foreseen in the analysis and the design of transducers for
      echographic applications in order to evaluate and/or optimize their performances.

PMID- 8306308
TI  - 3D modeling in myocardial 201TL SPECT.
AB  - A method to model the left ventricular myocardium in thallium-201 Single Photon
      Emission Computed Tomography (SPECT) is presented. This method is based on the
      fitting of the morphological skeleton of the left ventricle to a truncated
      bullet. This automatic approach would provide a more reproducible visualization
      of the organ for clinical applications.

PMID- 8306309
TI  - Validation of an MRI/PET landmark registration method using 3D simulated PET
      images and point simulations.
AB  - Three-dimensional (3D) simulated PET images generated from MRI were used to
      validate a multimodality registration technique based on the identification of
      internal anatomical landmarks. In addition, point-based simulations were compared
      with registration datasets acquired over 3 yr of routine use of the technique.
      Registration errors were found to range from 1.0 mm at the brain centre to 2.8 mm
      in each dimension at the brain surface.

PMID- 8306310
TI  - Accurate combination of CT and MR data of the head: validation and applications
      in surgical and therapy planning.
AB  - A method is presented for the accurate combination of magnetic resonance (MR) and
      computed tomographic (CT) images of the head. Our technique is based on user
      identified 3D landmarks followed by data combination and display as adjacent
      slices, a single fused slice representation, colour overlay and three-dimensional
      (3D) rendered scenes. Validation with a point phantom and computer simulation has
      established the relationship of registration accuracy with point location
      accuracy, the number of points used and their spatial distribution. The technique
      is in clinical use in the planning of skull base surgery, transferring MR images
      acquired without a stereotaxic frame to stereotaxic space, and staging and
      planning therapy of nasopharyngeal tumours.

PMID- 8306311
TI  - 3D simulation of PET brain images using segmented MRI data and positron tomograph
      characteristics.
AB  - A 3D simulation procedure has been developed to generate simulated PET brain
      images from MRI data. MRI slices were segmented into gray matter, white matter,
      CSF structures, and assigned with radionuclide distributions. Projections through
      these regions were generated according to physical characteristics of a positron
      tomograph, including 3D sampling and resolution, attenuation, scatter, randoms,
      and counting statistics. The projection data were then reconstructed by filtered
      backprojection. The procedure was validated with a cold spot phantom. Simulated
      PET images for cerebral blood flow or metabolism are presented, along with a
      brief discussion of some applications and limitations.

PMID- 8306312
TI  - 3D simulations of radiotracer uptake in deep nuclei of human brain.
AB  - The accuracy of Positron Emission Tomography (PET) for measuring in vivo
      concentrations of radiolabelled pharmaceuticals is affected by the limited
      tomograph resolution. Using computer simulations, we developed a model
      reproducing the distribution of the tracer [18F]fluoroDOPA which is specifically
      taken up in the normal human striatum. Validation of the model was performed by
      comparing the simulated images with real PET scans of the same brain. The
      simulation was used to examine the effect of axial displacement of the brain
      relative to the PET imaging planes, and that of image contrast on signal recovery
      (partial volume effects).

PMID- 8306313
TI  - 3D geometrical features of anatomic structures: the example of the ulna and
      radius bones.
AB  - This paper addresses two important issues of three-dimensional (3D) natural shape
      analysis. The first concerns the segmentation of these shapes into 3D primitives
      and the second deals with their geometric characterisation by means of intrinsic
      features. Restricting ourselves to 3D objects formed from two-dimensional (2D)
      cross-sectional adjacent slices (i.e., long bones), we present a method of
      contextual classification and results concerning the ulnar bone. With respect to
      the second issue, a curvature-torsion analysis of the medullar axis is introduced
      and the results are represented by means of torsion images. A first application
      to ulnar structures is given. It is shown that radius bones have zero torsion and
      that their curvatures can be studied in 2D. A preliminary statistical study of
      the 2D curvature of the radius is also presented.

PMID- 8306314
TI  - Interactive morphological watershed analysis for 3D medical images.
AB  - Combining automatic processing with interactive techniques is proving to be an
      effective strategy for segmenting complex three-dimensional (3D) medical images.
      We describe a general 3D image segmentation strategy that draws upon
      morphological watershed analysis and operator-defined topological cues. Watershed
      analysis segments a gray scale image into different regions by interpreting the
      image as a topographic surface. Using readily available interactive techniques, a
      human operator can easily define cues that specify spatial relationships between
      regions of interest. Cues defined in such a manner greatly assist subsequent
      watershed analysis. Results using 3D cardiac images show that this method leads
      to rapid robust image segmentation.

PMID- 8306315
TI  - Extraction of functional volumes from medical dynamic volumetric data sets.
AB  - A method based on factor analysis is presented to process dynamic volumetric (t +
      3D) data sets acquired for flow, excretion, or metabolic studies. It estimates a
      reduced number of underlying physiological kinetics and their associated spatial
      distributions, corresponding to functional volumes, using dedicated algorithms.
      The global (t + 3D) approach is shown to be superior to the conventional one,
      which repeats estimations on each (t + 2D) data set, obtained for each slice or
      projection of the volume.

PMID- 8306316
TI  - Computer-assisted 3D analysis of cell distributions in the normal and epileptic
      cerebral cortex: description of a methodology in progress.
AB  - This paper describes software routines that (a) visualizes a stack of several
      thousands of aligned sequential photographic two-dimensional (2D) images stored
      in an image processing system; (b) creates a data base containing information
      about objects identified sequentially from the 2D images; (c) transfers the data
      base to a graphical terminal; (d) reconstructs a three-dimensional (3D) object
      space; and (e) supports on-line interaction between the image processing system
      and the graphical terminal. As an application example, the cell content of a
      prism of motor cerebral cortex of the cat is reconstructed. Preliminary results
      from reconstructing human epileptic temporal cortex (cortical microdysgenesia)
      are also reported.

PMID- 8306317
TI  - Loss of heterozygosity on chromosome 13 is common only in the biologically more
      aggressive subtypes of ovarian epithelial tumors and is associated with normal
      retinoblastoma gene expression.
AB  - We examined the frequencies of loss of heterozygosity on chromosome 13 in 77
      primary ovarian epithelial tumors subdivided into cystadenomas, tumors of low
      malignant potential, low grade carcinomas, and high grade carcinomas. Such losses
      were found in approximately 50% of high grade carcinomas but were not detected in
      any of the other tumor subtypes (P < 0.0001), suggesting a strong association
      between these abnormalities and the high grade carcinoma phenotype. The tumors
      were also examined for abnormalities in expression of the retinoblastoma
      susceptibility gene (RB). This was assessed by immunohistochemical staining of
      archival tumor sections with a polyclonal antibody directed against both the
      phosphorylated and the underphosphorylated forms of the RB protein. Most of the
      tumors, including those with allelic deletions on chromosome 13, showed normal RB
      nuclear protein staining patterns. We conclude that loss of RB expression is not
      a frequent event in primary ovarian carcinomas and that this gene is probably not
      the target of the frequent allelic deletions on chromosome 13 found in high grade
      ovarian carcinomas.

PMID- 8306318
TI  - Evidence of functional RB protein in epithelial ovarian carcinomas despite loss
      of heterozygosity at the RB locus.
AB  - The presence of retinoblastoma (RB) protein was evaluated by immunohistochemical
      staining and correlated with loss of heterozygosity (LOH) at the RB locus in 52
      primary epithelial ovarian carcinomas. Forty-eight tumors were informative at the
      RB locus by molecular genetic analysis. Twenty-five tumors (52%) showed loss of
      heterozygosity at the RB locus. RB protein expression was found in 23 of these
      tumors. The remaining two tumors were negative for RB protein product by
      immunohistochemical staining. All 23 tumors showing no LOH at the RB locus had a
      normal RB protein pattern. All but three tumors revealed either no LOH with any
      marker or, if LOH was found for one chromosome 13 marker, all other informative
      markers also showed LOH. The three recombinant tumors included two which retained
      alleles at one or more loci distal and one which retained alleles proximal to the
      RB locus. LOH at the RB locus was significantly more common in invasive high
      grade (grades 3 and 4) tumors as compared to invasive low-grade (grades 1 and 2)
      tumors (P < 0.001). Our data suggest that while molecular genetic studies reveal
      frequent LOH at the RB locus, particularly in high-grade tumors, normal RB
      protein expression is present in the majority (96%) of these tumors. This implies
      that another, unidentified, gene or genes located on chromosome 13 may be
      important in the progression of most epithelial ovarian carcinomas. Additionally,
      it is likely that the specific chromosome 13 alteration(s) associated with
      sporadic ovarian neoplasms will be extremely difficult to identify using allelic
      loss and deletion mapping studies.

PMID- 8306319
TI  - The role of p53 in spontaneous and radiation-induced apoptosis in the
      gastrointestinal tract of normal and p53-deficient mice.
AB  - Three h after whole-body irradiation (8 Gy) of C57BL x DBA/2 F1 mice, p53 protein
      was expressed strongly in the stem cell compartment of the small intestine but at
      lower levels in the colon. At this time, apoptotic cells were also observed in
      the stem cell position of the small intestine, with fewer in the colon. In mice
      without copies of the p53 gene (nulls), the levels of spontaneous apoptosis, in
      both the small intestine and the colon, were not different from wild-type.
      Irradiation of the nulls with 8 Gy of gamma-rays failed to induce any further
      apoptosis: the loss of p53 essentially rendered the epithelial cells, from both
      the small intestine and the colon, radioresistant. The response of the epithelial
      stem cells of the small intestine suggests that p53 may play a role in the
      deletion of damaged cells with carcinogenic potential, whereas this process is
      limited in the colon.

PMID- 8306320
TI  - Evaluation of the potential role of class II histocompatibility antigen HLA-DR in
      platelet/tumor cell interaction.
AB  - It has been reported that HLA-DR is a potent inducer of thrombin generation.
      Human colorectal cells (GEO, WiDr, DLD-1, and MIP) that lack the constitutive
      expression of HLA-DR cause platelet aggregation through a thrombin-dependent
      mechanism. Treatment with recombinant human gamma-interferon induced the
      expression of HLA-DR in the GEO, WiDr, and DLD-1 cells, whereas the MIP cell line
      remained HLA-DR negative. The concurrent analysis of tumor cell/platelet
      interaction after gamma-interferon treatment showed a decrease in platelet
      proaggregating activity of either the responsive GEO (highly expressing HLA-DR)
      or the unresponsive MIP (HLA-DR negative) cells. Furthermore, the DLD-1
      (moderately expressing HLA-DR) cells showed an increase of proaggregating
      activity after gamma-interferon treatment, whereas WiDr (highly expressing HLA
      DR) cells did not modify their activity. These results suggest a lack of a role
      of HLA-DR in the in vitro platelet proaggregating activity of human colorectal
      tumor cells.

PMID- 8306321
TI  - Lack of neurotoxicity of oral bisacetatoamminedichlorocyclohexylamine
      platinum(IV) in comparison to cisplatin and tetraplatin in the rat.
AB  - This study compared the effect on sensory nerve conduction velocity in the hind
      limb of chronically treated age-matched rats of a novel lipophilic p.o. platinum
      complex [bisacetatoamminedichlorocyclohexylamine-platinum(IV)], with that of
      neurotoxic platinum complexes cisplatin and tetraplatin. Tetraplatin (i.p.) first
      caused slowing of sensory nerve conduction (-14.4% of controls; P < 0.05) at a
      dose (1 mg/kg) that was free of constitutional toxicity. Cisplatin (i.p.) first
      caused slowing of sensory nerve conduction (-17.5% of control; P < 0.05) at a
      dose (2 mg/kg) approximating the maximal tolerated dose.
      Bisacetatoamminedichlorocyclohexylamineplatinum(IV) (p.o.) showed no slowing of
      sensory nerve conduction either after 20.5 weeks of treatment at a dose (25
      mg/kg) approximating the maximal tolerated dose or after 6 weeks of treatment at
      a dose (50 mg/kg) which eventually proved intolerable. In conclusion, p.o.
      bisacetatoamminedichlorocyclohexylamineplatinum(IV) shows a lack of neurotoxicity
      compared to parenterally administered cisplatin and tetraplatin at the maximal
      tolerated dose in rats.

PMID- 8306322
TI  - Specific inhibition of pre-ribosomal RNA processing in extracts from the
      lymphosarcoma cells treated with 5-fluorouracil.
AB  - To elucidate the molecular mechanism by which the potent anticancer drug, 5
      fluorouracil (5-FUra), inhibits cell proliferation, the effect of its metabolite,
      5-fluorouridine triphosphate, on transcription of rat rRNA gene and processing of
      pre-rRNA was investigated in S-100 extract from the mouse lymphosarcoma cells.
      The in vitro processing of pre-rRNA substrate synthesized from the T3 promoter
      occurred at the correct primary processing site. Replacement of UMP with 5
      fluorouridine monophosphate in the rRNA substrate did not affect the pre-rRNA
      processing. Similar result was obtained when coupled transcription-processing was
      studied. When the coupled reaction was examined using extracts from the cells
      treated with 5-FUra, rRNA processing was abolished whereas transcription of rRNA
      gene was unaffected. Treatment of cells with thymidine along with 5-FUra did not
      reverse the inhibitory effect of the drug on rRNA processing. In contrast to the
      effect on rRNA processing, treatment of cells with 5-FUra did not impede the 3'
      end processing of pre-mRNA. These data show that inhibition of pre-rRNA
      processing is a major mechanism of action of 5-FUra and suggest that the activity
      and/or synthesis of a trans-acting factor(s) involved in this reaction is altered
      by the anticancer drug.

PMID- 8306323
TI  - Frequent loss of chromosome 9 in human primary non-small cell lung cancer.
AB  - We analyzed the pattern of allelic loss on chromosome 9 in 40 primary human non
      small cell lung cancers including 16 squamous cell, 18 adeno-, and 6 large cell
      carcinomas. Using 24 polymorphic microsatellite markers spanning chromosome 9, we
      found that 27 of 40 (67.5%) of these neoplasms displayed loss of heterozygosity
      (LOH) on chromosome 9. Most tumors showed LOH for all informative markers on both
      chromosomal arms, whereas five tumors demonstrated partial LOH on chromosome 9.
      In four of these tumors, allelic loss was limited to the 9p arm, whereas in the
      remaining specimen, LOH extended from 9p21-22 to terminal 9q. These five tumors
      delineate a minimal area of loss at 9p21-22, which includes a previously defined
      tumor suppressor gene locus. We have identified a distinct region of loss on
      chromosome 9p commonly involved in non-small cell lung cancer tumorigenesis.

PMID- 8306324
TI  - Prostacyclin as an indicator of preadipocyte transformation: studies in vivo by
      microdialysis and in vitro.
AB  - Nontransformed (Ob1771) and polyoma virus-transformed (Ob17PY) mouse cells from
      the preadipocyte Ob17 clonal line have been compared in their ability to release
      prostaglandins in vitro as well as in vivo as assayed by in situ microdialysis.
      Prostaglandin FE2, prostaglandin-2 alpha and mainly prostacyclin are released in
      larger amounts (4- to 10-fold) by Ob17PY cells in vitro and Ob17PY-induced tumors
      in vivo as compared to Ob1771 preadipocytes in vitro and periepididymal adipose
      tissue in vivo. In contrast to Ob1771 preadipocytes, none of these prostanoids
      appear to be involved in the control of proliferation or differentiation of
      Ob17PY cells in serum-free culture medium. However, prostacyclin, the level of
      which is the most affected by transformation, might be considered as a valuable
      indicator of fibrosarcoma development.

PMID- 8306325
TI  - Tumor-suppressive activity of N03 gene product in v-src-transformed rat 3Y1
      fibroblasts.
AB  - The expression of the N03 gene was significantly reduced in a variety of
      transformed cells, compared with that in parental rat 3Y1 fibroblasts. To
      understand the possible role(s) of its product, we have obtained transfectants
      expressing N03 gene from v-src-transformed 3Y1 cells. Two clones, which
      overexpressed N03 mRNA, showed a flatter phenotype, a reduced rate of growth, and
      a decreased ability to grow in soft agar. One of the clones which maintained N03
      expression was completely suppressed in forming tumors in nude mice. These data
      suggest that the N03 gene product may have a suppressive ability on transformed
      phenotypes.

PMID- 8306326
TI  - Analysis of the p53 gene and its expression in human glioblastoma cells.
AB  - Chromosome 17p has been shown to be an early and frequent target for loss of
      heterozygosity through mitotic recombination in astrocytomas. These losses are
      frequently accompanied by point mutations in the p53 gene of the remaining
      allele, resulting in loss of wild type p53 function. However, a fraction of
      astrocytomas retain constitutional heterozygosity and do not have p53 mutations;
      some of these lose wild type p53 activity through binding to the protein product
      of amplified mdm2 genes. To test whether loss of wild type p53 biological
      function is a necessary step in astrocytoma progression we analyzed p53
      expression and biological function in 13 glioma cell lines. All the cell lines
      expressed a 2.8-kilobase p53 transcript and showed various amounts of p53 protein
      by immunoprecipitation, except for cell line LN-Z308 which had only a small
      truncated p53 mRNA and no protein expression. To test whether the p53 expressed
      in these cell lines was functionally wild type or mutant we transfected them with
      a plasmid construct harboring a chloramphenicol acetyltransferase (CAT) reporter
      gene under the control of transcriptional elements that are induced by wild type
      but not mutant p53. Four lines were shown to retain wild type p53 function.
      Sequencing of the p53 gene in two of these cell lines confirmed the wild type
      genotype. These results show that inactivation of the p53 gene is not an
      obligatory step in glioblastoma genesis. This suggests either that two pathways
      (p53 inactivation dependent or independent) may lead to a tumor group classified
      histologically as glioblastoma or that in some cases p53 mutations are bypassed
      due to the presence of mutations in downstream effector genes.

PMID- 8306327
TI  - New directions in molecular medicine.

PMID- 8306328
TI  - Drug resistance: genotype versus phenotype--thirty-second G. H. A. Clowes
      Memorial Award Lecture.

PMID- 8306329
TI  - Blocking of in vitro DNA replication by deoxycytidine adducts of the mutagen and
      clastogen 2-bromoacrolein.
AB  - Calf thymus single-stranded DNA was modified with 2-bromoacrolein (2BA), a
      genotoxic metabolite of tris(2,3-dibromopropyl)phosphate. This DNA was used as a
      template for in vitro DNA replication by T7-polymerase and Klenow fragment of
      Escherichia coli DNA polymerase I. Increasing levels of 2BA modification led to
      decreased DNA synthesis as measured by [methyl-3H]dTTP incorporation. M13 mp19
      single-stranded DNA template modified with 2BA was used to determine the sites of
      termination of DNA replication by T7 polymerase and Klenow fragment of
      Escherichia coli DNA polymerase I. It was found that DNA replication stopped
      frequently before and occasionally opposite deoxycytidine nucleotides. These
      results indicated that an as yet unidentified deoxycytidine:2BA adduct may have
      been formed in the reaction of 2BA with M13 DNA. To investigate if such adducts
      were formed, we reacted 2BA with deoxycytidine in vitro at pH 4.4, and putative
      deoxycytidine:2BA adducts were isolated by high-performance liquid
      chromatography. They were characterized by 1H and 13C nuclear magnetic resonance
      and with fast atom bombardment mass spectrometry as two diastereomeric 3-bromo-7
      (beta-D-deoxyribofuranosyl)- 3,4-dihydro-2-hydroxy-(2H,7H)[1,6-a]pyrimidin-6-one
      adducts and a 3-bromo-7-(beta-deoxyribofuranosyl)-(4H,7H)-pyrimido[1,6
      a]pyrimidin-6 -one adduct. Only the latter adduct, however, was formed in the
      reaction of 2BA with calf thymus single-stranded DNA in vitro. Tris(2,3
      dibromopropyl)phosphate is clastogenic. Because clastogenicity may result from
      DNA adducts that block replication, the role of the presently identified
      deoxycytidine adducts of the reaction metabolite 2BA in the clastogenicity of
      tris(2,3-dibromopropyl)phosphate is discussed.

PMID- 8306330
TI  - The effect of the iron(III) chelator, desferrioxamine, on iron and transferrin
      uptake by the human malignant melanoma cell.
AB  - The mechanism of action of the clinically used iron(III) chelator,
      desferrioxamine (DFO), on preventing iron (Fe) uptake from transferrin (Tf) has
      been investigated using the human melanoma cell line SK-MEL-28. This
      investigation was initiated due to the paucity of information on the mechanisms
      of action of DFO in neoplastic cells and because recent studies have suggested
      that DFO may be a useful antitumor agent. The effect of DFO was dependent on
      incubation time. After a 2-h incubation, DFO acted like the extracellular
      chelators, EDTA and diethylenetriaminepentaacetic acid, because there was little
      inhibition of 59Fe uptake from Tf. In contrast, after a 24-h incubation, DFO (0.5
      mM) efficiently reduced internalized 59Fe uptake from Tf to 18% of the control
      value. These observations suggested the existence of a kinetic block to the entry
      of the apochelator to intracellular Fe pools and/or to the exit of the DFO-59Fe
      complex. Indeed, cellular fractionation demonstrated that, in contrast to the
      decrease in the percentage of 59Fe in the ferritin and membrane fractions, a
      marked increase in the percentage of 59Fe present in the ferritin-free cytosol
      occurred. These observations suggested an accumulation of the DFO-59Fe complex
      within the cell. The highly lipophilic Fe chelator, pyridoxal isonicotinoyl
      hydrazone, was far more effective than DFO at preventing 59Fe uptake from Tf,
      illustrating the importance of membrane permeability for effective Fe chelation.
      Desferrioxamine at a concentration of 1 mM decreased internalized 125I-Tf uptake
      to 70% of the control. However, the decrease in 59Fe uptake observed could only
      be partially accounted for by a decrease in Tf uptake, and it appeared that DFO
      was chelating 59Fe at an intracellular site consistent with the transit Fe pool.
      The results are discussed in the context of the use of Fe chelators as effective
      antineoplastic agents.

PMID- 8306331
TI  - Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and
      ursolic acid.
AB  - A methanol extract of the leaves of the plant Rosmarinus officinalis L.
      (rosemary) was evaluated for its effects on tumor initiation and promotion in
      mouse skin. Application of rosemary to mouse skin inhibited the covalent binding
      of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by
      B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol
      B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by
      promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly
      for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel
      group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min
      prior to each application of B(a)P, the number of tumors per mouse was decreased
      by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited
      TPA-induced ornithine decarboxylase activity, TPA-induced inflammation,
      arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced
      tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA
      twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse.
      Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary
      together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA
      induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical
      application of carnosol or ursolic acid isolated from rosemary inhibited TPA
      induced ear inflammation, ornithine decarboxylase activity, and tumor promotion.
      Topical application of 1, 3, or 10 mumol carnosol together with 5 nmol TPA twice
      weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited
      the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical
      application of 0.1, 0.3, 1, or 2 mumol ursolic acid together with 5 nmol TPA
      twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors
      per mouse by 45-61%.

PMID- 8306332
TI  - Phase I and pharmacokinetic study of ormaplatin (tetraplatin, NSC 363812)
      administered on a day 1 and day 8 schedule.
AB  - Ormaplatin (tetraplatin, NSC 363812) is a platinum(IV) analogue that is active
      against cisplatin-resistant cell lines in preclinical models. A schedule
      previously shown to be active and well tolerated for cisplatin was evaluated in
      26 patients. Ormaplatin was administered over a dose range of 4.4-60.8 mg/m2 i.v.
      given over 30 min on a day 1 and day 8 schedule every 28 days. Twenty-three
      patients had received prior chemotherapy, and the median performance status was
      1. Nausea/vomiting (> or = grade 2) occurred in 40% of patients but was well
      controlled with standard antiemetic therapy. One patient had grade 2 renal
      toxicity and 1 patient had grade 3 hepatotoxicity (grade 2 pretreatment). No
      toxicity limited the dose given during the first course. With repeated drug
      administration delayed severe neurotoxicity developed in 4 patients, manifested
      as a sensory polyneuropathy in 3 patients and a possible autonomic neuropathy in
      one. Prospective nerve conduction studies did not detect subclinical neuropathy
      prior to the onset of symptoms. Patients who received cumulative doses above 200
      mg/m2 were at increased risk for developing neurotoxicity. Plasma elimination of
      ultrafilterable platinum (measured by atomic absorption spectrometry) was
      biphasic with a harmonic mean terminal half-life of 15.8 h. The mean total body
      clearance and renal clearance of ultrafilterable platinum were 173 and 29.8
      ml/min/m2, respectively. Thus, renal clearance accounted for 16% of total
      clearance suggesting that extensive protein/tissue binding was responsible for
      the majority of platinum clearance. Approximately 60% of the platinum is protein
      bound (one-half irreversibly) at the end of the infusion. Pharmacokinetic
      parameters were not dose dependent. No pharmacokinetic parameters were more
      predictive of neurotoxicity than the cumulative ormaplatin dose. A phase II dose
      cannot be recommended on this schedule because severe and unpredictable
      neurotoxicity precludes the administration of more than three cycles at the three
      highest doses levels tested.

PMID- 8306333
TI  - A prospective cohort study on the relation between meat consumption and the risk
      of colon cancer.
AB  - The high incidence of colon cancer in affluent societies has often been
      attributed to a high fat diet and, more in particular, the consumption of meat.
      The association of the consumption of meat and the intake of fat with risk of
      colon cancer was investigated in a prospective cohort study on diet and cancer,
      which is being conducted in the Netherlands since 1986 among 120,852 men and
      women, aged 55-69. The analysis was based on 215 incident cases of colon cancer
      (105 men and 110 women) accumulated in 3.3 years of follow-up, excluding cases
      diagnosed in the first year of follow-up. Dietary habits were assessed at
      baseline with a 150-item semiquantitative food frequency questionnaire. No trends
      in relative rates of colon cancer were detected for intake of energy or for the
      energy-adjusted intake of fats, protein, fat from meat, and protein from meat.
      Consumption of total fresh meat, beef, pork, minced meat, chicken, and fish was
      not associated with risk of colon cancer either. Processed meats, however, were
      associated with an increased risk in men and women (relative rate, 1.17 per
      increment of 15 g/day; 95% confidence interval, 1.03-1.33). The increased risk
      appeared to be attributable to one of the five questionnaire items on processed
      meat, which comprised mainly sausages. This study does not support a role of
      fresh meat and dietary fat in the etiology of colon cancer in this population. As
      an exception, some processed meats may increase the risk, but the mechanism is
      not yet clear.

PMID- 8306335
TI  - Preclinical evaluation of WR-151327: an orally active chemotherapy protector.
AB  - Clinical trials are in progress to evaluate radio- and chemoprotection by the
      aminothiol 2-[(3-aminopropyl)amino]ethanethiol-dihydrogen phosphate ester (WR
      2721; amifostine). Phase II and III clinical studies have demonstrated that i.v.
      administered WR-2721 protects against the toxicities of cis
      diamminedichloroplatinum (II) and cyclophosphamide. In preclinical murine
      studies, we have now further characterized the chemoprotective properties of WR
      2721, and have evaluated the protective ability of the related aminothiol S-3-(3
      methylaminopropylamino)propylphosphorothioic acid (WR-151327) following p.o.
      administration. The P388 leukemia (i.p. tumor-i.p. cytotoxic drug on Day 1 after
      tumor) was used to determine antitumor efficacy. Single dose pretreatment with
      i.p. WR-2721 protects normal mouse tissues against the chemotoxicities of
      mitomycin C, cis-diammine(cyclobutanedicarboxylato)platinum (II), and
      doxorubicin. Bone marrow suppression and cytotoxic drug-induced lethality were
      reduced, without compromising P388 antitumor activity. Pretreatment with a single
      p.o. dose of WR-151327 was as effective as i.p. WR-2721 in protecting against the
      myelotoxicity and lethality of mitomycin C, cis-diamminedichloroplatinum (II),
      and cis-diammine(cyclobutanedicarboxylato)platinum (II), while P388 antitumor
      activity was maintained. These data support the clinical development of WR-151327
      as a p.o. administered chemotherapy protector.

PMID- 8306334
TI  - Antitumor activity and biochemical effects of aphidicolin glycinate (NSC 303812)
      alone and in combination with cisplatin in vivo.
AB  - Aphidicolin, an inhibitor of DNA polymerases alpha and delta, is cytotoxic in
      vitro against tumor cells. The poor solubility of aphidicolin has led to the
      development of aphidicolin glycinate (AG; NSC 303812), a water soluble ester
      currently in early clinical trials. The antitumor activity of AG was investigated
      in a series of transplantable murine tumors in vivo. The drug demonstrated
      activity against the i.p. implanted B16 melanoma, producing maximum increased
      life spans of 75% following i.p. administration every 3 h for three doses on days
      1-9. Treatment schedules involving both single injections per day on days 1-9 and
      multiple injections per day on days 1, 5, and 9 were less effective, indicating
      that this antitumor activity is schedule dependent. Similarly, greater activity
      was observed against the i.p. M5076 sarcoma when three daily injections were
      given on days 1-9 (57% increased life span) than with a single injection either
      on days 1-9 (36% increased life span) or on days 1, 5, 9, and 13 (inactive).
      Further scheduling studies in the s.c. M5076 sarcoma model showed that a 7-day
      infusion was superior to both a 24-h infusion and a 7-day course of three bolus
      treatments per day. On the assumption that DNA polymerase inhibition is the basis
      for this antitumor activity, inhibition of DNA synthesis in BALB/c x DBA/2 F1
      mice was investigated by measuring incorporation of [3H]thymidine (20 microCi,
      i.v.) into DNA of spleen and jejunum. At 2 h after administration of AG,
      inhibition of DNA synthesis was dose dependent (median inhibitory dose, 60 mg/kg
      in both tissues) and was > 99% at 300 mg/kg. The inhibition was rapid in onset;
      AG (100 mg/kg i.p.) produced maximal (> 98%) inhibition in both tissues at 30
      min. Recovery occurred in the intestine within 16 h; in spleen recovery was
      delayed to 24 h, and was followed by a rebound incorporation at 48 h (203%). A
      comparison of the inhibition of thymidine incorporation in tumor cells (B16
      melanoma and P388 leukemia) and normal jejunum revealed no significant
      differences in the extent of inhibition or the rapidity of recovery in these
      tissues. The rapid recovery of DNA synthesis inhibition supports the use of
      prolonged infusion schedules in clinical trials, but the lack of evidence of
      selectivity for tumor cells suggests that AG may be of limited therapeutic value
      as a single agent. Thus, we evaluated AG in combination with cisplatin in an in
      vivo model of cisplatin refractory human ovarian cancer.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8306336
TI  - Cellular pharmacology of N1- and N8-aziridinyl analogues of spermidine.
AB  - We have previously described the synthesis and cytotoxic properties of 2
      polyamine analogues in which either the N1- or N8-amino group of spermidine was
      replaced by the alkylating moiety, aziridine. However, the mechanisms by which
      these aziridinyl analogues of spermidine inhibit cell growth remain unknown. As a
      result, we have studied: (a) the effect of pretreatment with difluoromethyl
      ornithine (DFMO) and coincubation with exogenous spermidine on cytotoxicity
      induced by the aziridinyl spermidines; (b) the reversibility of the cytotoxicity
      induced by the aziridinyl spermidines; (c) the accumulation of N1- and N8
      aziridinyl spermidine by cells and the effects of DFMO on this process; and (d)
      the impact of N1- and N8-aziridinyl spermidine on cellular polyamine pools and on
      cellular accumulation of spermidine. The cytotoxicity induced by these 2
      aziridinyl derivatives of spermidine [concentration required to inhibit cell
      growth or incorporation of radiolabeled precursor into trichloroacetic acid
      precipitable material by 50% (IC50) N1 = 0.2 microM, IC50 N8 = 0.4 microM)] was
      potentiated by pretreatment of L1210 cells for 24 h with 100 microM DFMO (IC50 N1
      = 0.05 microM, IC50 N8 = 0.15 microM) and was prevented by coincubation with 3.7
      microM spermidine (IC50 N1 = 1.1 microM, IC50 N8 = 2.4 microM). In contrast,
      similar pretreatment with DFMO or coincubation with spermidine had no effect on
      the cytotoxicity induced by the aziridine-containing alkylating agent, N,N',N"
      triethylenethiophosphoramide (thiotepa) (IC50 = 2.4 microM). The cytotoxicity
      induced by 24-h incubation with either N1- or N8-aziridinyl spermidine was not
      altered by removal of those compounds and incubating treated cells in medium
      augmented with 3.7 microM spermidine. However, and as expected, similar maneuvers
      did not reverse the cell growth-inhibitory effect induced by 24-h incubation with
      100 microM DFMO. Cellular accumulation of both N1- and N8-aziridinyl spermidine
      increased with increasing extracellular concentrations. N1-Aziridinyl spermidine
      was accumulated to a greater degree than was the N8-analogue, achieving up to 6
      fold higher intracellular concentrations at the same extracellular concentration.
      Cellular accumulation of both aziridinyl compounds was greatly enhanced by 24-h
      pretreatment with DFMO. Both N1- and N8-aziridinyl spermidine inhibited the
      uptake of spermidine in a dose-dependent manner. The perturbation of polyamine
      biochemistry by the test compounds was characterized by their ability to deplete
      cellular putrescine, as well as spermidine and spermine. These results imply that
      the cytotoxic mechanism of the aziridinyl spermidine analogues is, to a great
      extent, dependent on their polyamine nature and may imply selectivity for rapidly
      growing and neoplastic cells.

PMID- 8306337
TI  - Quantitative and qualitative aspects of topoisomerase I and II alpha and beta in
      untreated and platinum/cyclophosphamide treated malignant ovarian tumors.
AB  - Quantitative and qualitative aspects of topoisomerase (Topo) I and II were
      studied in 17 malignant ovarian tumors [eight untreated and nine after
      platinum/cyclophosphamide (Pt/Cy) chemotherapy]. Median Topo II catalytic
      activity was lower (P < 0.05) in tumors after Pt/Cy chemotherapy in comparison to
      untreated tumors, while no differences were found for Topo I catalytic activity
      in tumors before and after chemotherapy, as was also found in a previous study
      (Van der Zee et al. Cancer Res., 51: 5915-5920, 1991). Teniposide (VM-26)-induced
      cleavable complex formation correlated (r = 0.60; P < 0.05) with Topo II
      activity, while Topo II decatenation activity was equally but incompletely
      inhibited by VM-26 in all tumors. No differences were found in Topo II cleavage
      site patterns in plasmid BR322 DNA for all tumors using an indirect end-labeling
      procedure. Cleavable complex formation of Topo I by camptothecin (Cpt) did not
      correlate with Topo I catalytic activity, while Topo I catalytic activity could
      equally and completely be inhibited by Cpt. By Western blotting, Topo II alpha
      protein expression was detected in four of eight untreated tumors and three of
      nine tumors after Pt/Cy chemotherapy, whereas in all tumors a M(r) 150,000
      degradation product of Topo II beta was detected. Topo I protein was detected in
      all tumors at varying levels, but the protein levels did not correlate with Topo
      I catalytic activity or cleavable complex formation by Cpt. Our study shows that
      Topo I and II, isolated from human malignant tumors, can be stimulated by Cpt and
      VM-26, respectively, to induce DNA cleavage, which suggests that topoisomerases
      are real targets for chemotherapy in patients with ovarian cancer. From in vitro
      data from the literature it appears that the cleavable complex assay reflects
      both quantitative and qualitative changes as well as changes in the
      phosphorylation state of Topo I and II. In combination with the feasibility of
      the cleavable complex assay for Topo I and II in human malignant tumors, which
      was found in the present study, it appears that at present the determination of
      cleavable complex formation by tumors seems to be the most promising parameter of
      Topo I or II expression in human tumors to be related to response to Topo I- or
      II-targeted chemotherapy.

PMID- 8306338
TI  - Altered subcellular distribution of topoisomerase II alpha in a drug-resistant
      human small cell lung cancer cell line.
AB  - A drug-resistant human small cell lung cancer cell line, H209/V6, selected in the
      presence of increasing concentrations of 9-(4,6-O-ethylidene-beta-D
      glucopyranosyl)-4'-demethylepipodophylloto xin (VP-16) from parental H209 cells,
      is 22-, 9-, and 4-fold resistant to VP-16, 4'-(9-acridinyl-amino)methanesulfon-m
      anisidide, and doxorubicin, respectively, but not cross-resistant to 1,4
      dihydroxy-5,8-bis((2-[(2-hydroxyethyl)amino] ethyl]-amino)-9,10-anthracenedione.
      These cells do not overexpress P-glycoprotein or the multidrug resistance
      associated protein. Immunoblotting demonstrates that H209 cells contain the M(r)
      170,000 isoform of topoisomerase II (topo II), while H209/V6 cells have a M(r)
      160,000 enzyme but none of the M(r) 170,000 isoform. The cell lines have equal
      amounts of topo II beta. The H209/V6 cells have a 5-fold decrease in total
      immunoreactive topo II alpha. The catalytic and VP-16-induced DNA cleavage
      activities of the topo II present in 0.35 M NaCl nuclear extracts are decreased 2
      to 3-fold in the drug-resistant cell line. This decrease in enzymatic activity
      is not consistent with either the 22-fold VP-16 resistance of the H209/V6 cell
      line or the approximately 5-fold decrease in immunoreactive topo II alpha in the
      cells. The M(r) 160,000 isoform from the H209/V6 cell line and the M(r) 170,000
      enzyme from the parental cell line were purified so that the enzymatic activity
      of the 2 isoforms could be evaluated. The catalytic activities of the purified
      isoforms were found to be very similar. The drug-induced DNA cleavage activity of
      the M(r) 160,000 enzyme was reduced compared to the M(r) 170,000 enzyme. However,
      as with the nuclear extracts, the differences in enzymatic activity of the
      purified enzymes are considerably less than the level of drug resistance.
      Investigations of the subcellular localization of topo II by immunocytochemical
      techniques and cytoplasm/nuclear fractionation studies demonstrated that the M(r)
      160,000 topo II alpha-related enzyme is primarily localized in the cytoplasm,
      while the M(r) 170,000 topo II alpha enzyme and topo II beta are located in the
      nucleus. These data imply that the deleted sequence in the M(r) 160,000 enzyme is
      not necessary for catalytic activity but is required to facilitate nuclear
      localization.

PMID- 8306339
TI  - Effect of human natural killer cells on the metastatic growth of human melanoma
      xenografts in mice with severe combined immunodeficiency.
AB  - An in vivo model for human melanoma was established with the growth of CR3 and
      DE5 human melanoma tumor cells following i.v. injection into C.B.-17 severe
      combined immunodeficient mice depleted of murine natural killer (NK) cells. The
      ability of human NK cells to mediate antitumor activity in vivo was investigated
      by evaluating the number of lung nodules and survival of mice given injections of
      human NK cells i.v. early after injection of CR3 tumor cells. Under these
      conditions, human NK cells effectively reduced lung nodule counts and prolonged
      survival when coinjected with interleukin 2 (IL-2). Multiple injections of IL-2
      given during the first 16 h post-NK injection did not further enhance the tumor
      reduction. Significantly increased antitumor activity against CR3 tumor cells in
      vivo was observed in mice receiving NK cells coinjected with IL-2 and interleukin
      12 (IL-12) in comparison to NK cells and IL-2 only. However, coinjection of IL-12
      with human NK cells alone did not reduce the tumor burden. These results
      demonstrate the antitumor activity of human NK cells against human melanoma in
      severe combined immunodeficient mice and its augmentation by IL-2, alone or in
      combination with IL-12, suggesting that this model can be used to further
      investigate the interaction between human NK cells and human tumors.

PMID- 8306340
TI  - Cytotoxic efficacy of 9-nitrocamptothecin in the treatment of human malignant
      melanoma cells in vitro.
AB  - In a recent study, we showed that the plant alkaloid camptothecin (CPT) and its
      derivatives 9-nitro-CPT (9NC) and 9-amino-CPT (9AC) inhibit growth of both human
      melanocytes (MEL cells) and their malignant counterparts, malignant melanoma
      (BRO) cells in vitro. This growth inhibition was accompanied by an increase in
      the size of BRO cells followed by death, whereas cell size increase and death
      were not observed in MEL cells. In this study, we have extended those
      investigations to identify parameters and factors that can modulate the cytotoxic
      action of 9NC against BRO cells in culture. MEL cells treated with 9NC accumulate
      at the S/G2 boundary of the cell cycle and remain there for a prolonged period of
      time with only a small number of cells dying by apoptosis. The extent of
      accumulation correlates with the length of 9NC treatment and/or 9NC concentration
      in the cell culture. Furthermore, treatment with low 9NC concentrations for a
      prolonged time or treatment with high drug concentrations results in a fraction
      of MEL cells with hyperdiploidy. In contrast, 9NC-treated BRO cells are arrested
      in the S phase before they die by apoptosis. Interestingly, lower 9NC
      concentrations are more effective than higher concentrations in inducing
      apoptosis. Once 9NC initiates the process of apoptosis in BRO cells, these cells
      are irrevocably committed to it and continue to die even after removal of the
      drug from the culture. The drug effectiveness to induce apoptosis correlates with
      the stage of the S phase, in which it affects DNA replication, with late stages
      resulting in higher numbers of apoptotic cells. Finally, although various 9NC
      concentrations result in inhibition of BRO cell proliferation, higher 9NC
      concentrations produce more enlarged BRO cells as assessed by microscopy. Taken
      together, these observations provide useful information for clinical application
      of 9NC as a chemotherapeutic agent against malignant melanoma.

PMID- 8306341
TI  - Human interleukin-3 stimulates a phosphatidylcholine specific phospholipase C and
      protein kinase C translocation.
AB  - Human interleukin-3 binds to a high affinity receptor composed of alpha- and beta
      subunits. The beta-subunit is responsible for signal transduction but does not
      contain any intrinsic tyrosine kinase activity or other consensus motifs related
      to intracellular signaling. Previous work using IL-3 dependent MO7E cells has
      suggested a major role only for non-receptor tyrosine kinase activation in IL-3
      signal transduction. We have shown, however, that engagement of the human
      interleukin-3 receptor induces the translocation of protein kinase C from the
      cytosol to the cell membrane in MO7E cells. This translocation is accompanied by
      rapid (2-5 min) accumulation of 1'2'-diacylglycerol (twice control values) in the
      absence of an increase in intracellular Ca2+. Prelabeling cells with [3H]glycerol
      or [3H]-choline demonstrated rapid release of [3H]phosphorylcholine and a
      decrease in [3H]glycerol-labeled phosphatidylcholine in response to IL-3
      stimulation. In addition, IL-3 did not induce phosphatidic acid accumulation, and
      the IL-3 induced diacylglycerol accumulation was blocked by p
      bromophenacylbromide (a phospholipase C inhibitor). It is thus likely that
      interleukin-3 is activating a phosphatidylcholine specific phospholipase C rather
      than a phospholipase D. Finally, genistein and herbimycin, specific tyrosine
      kinase inhibitors, inhibited both IL-3 induced protein kinase C translocation and
      the accumulation of diacylglycerol. Thus, IL-3 induced tyrosine phosphorylation
      may result in activation of a phosphatidylcholine phospholipase C and protein
      kinase C.

PMID- 8306342
TI  - Two molecular pathways to transitional cell carcinoma of the bladder.
AB  - Noninvasive transitional cell carcinomas of the bladder can have two distinct
      morphologies suggesting they contain different genetic alterations. Papillary
      transitional cell carcinomas (T(a) tumors) are often multifocal and only
      occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently
      progress to invasive disease. We examined 216 bladder tumors of various stages
      and histopathologies for two genetic alterations previously described to be of
      importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was
      observed in 24 of 70 (34%) T(a) tumors but was present in only 3 of 24 (12%) CIS
      and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3%) T(a) tumors
      contained a p53 gene mutation compared to 15 of 23 (65%) CIS and dysplasias (P <
      0.001), a frequency comparable to that observed in muscle invasive tumors (25 of
      49; 51%). The presence of p53 mutations in CIS and dysplasia could explain their
      propensities to progress since these mutations are known to destabilize the
      genome. Analysis of several tumor pairs involving a CIS and an invasive cancer
      provided evidence that the chromosome 9 alteration may in some cases be involved
      in the progression of CIS to more invasive tumors, in addition to its role in the
      initiation of T(a) tumors. However, the CIS and secondary tumor were found to
      contain different genetic alterations in some patients suggesting divergent
      progression pathways. Bladder carcinogenesis may therefore proceed through two
      distinct genetic alteration pathways responsible for generating superficial
      tumors with differing morphologies and pathologies.

PMID- 8306343
TI  - Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas.
AB  - Genetic alterations in the p53 and mdm2 genes have been reported to occur in soft
      tissue sarcomas. This study was designed to determine the prevalence and
      potential clinical value of detected molecular abnormalities and altered patterns
      of expression of mdm2 and p53 genes in adult soft tissue sarcomas. A cohort of
      211 soft tissue sarcomas from adults that were both clinically and pathologically
      well characterized was analyzed. Monoclonal antibodies directed against mdm2 and
      p53 proteins were used to measure overexpression of these proteins in the nuclei
      of cells from sections of these tumors. Seventy-six of 207 tumors had abnormally
      high levels of mdm2 proteins and 56 of 211 tumors overexpressed p53 protein.
      Twenty-two cases had abnormally high levels of both mdm2 and p53 proteins based
      upon immunoreactivity with these antibodies. There was a striking statistically
      significant correlation between the overexpression of p53 and mdm2 proteins in
      the same tumor and poor survival (P < 0.05) of the patients. A group of 73 soft
      tissue sarcomas was chosen for analysis using Southern blots, single strand
      conformation polymorphisms, and direct DNA sequencing to confirm mdm2 gene
      amplifications and p53 mutations and correlate these with the results of the
      immunoreactivities. The overexpression of p53 and mdm2 proteins in the nuclei of
      tumor cells did not always correlate well with gene amplification at the mdm2
      locus or mutation at the p53 gene. The possible reasons for these discrepancies
      are discussed.

PMID- 8306344
TI  - Proliferation kinetics of recruited cells in a mouse mammary carcinoma.
AB  - Solid tumors contain populations of proliferating (P) and quiescent (Q) cells.
      Shifting between these populations occurs continuously and cells are recruited
      from quiescence to proliferate (Q-->P) as a result of exogenously applied or
      endogenous cell depleting stimuli. Direct measurements of the proliferation
      kinetics of these Q-->P cells in solid tumors are difficult to make because of
      the much larger percentage of P-cells. In order to specifically analyze the
      kinetics of the Q-->P cells, double thymidine analogue labeling was used. This
      was accomplished by first labeling in vivo all of the P-cells in MCaK tumors
      using continuous exposure to chlorodeoxyuridine (CldUrd) administered by a
      minipump over 21 h. About 75% of the aneuploid cells are P-cells based on CldUrd
      labeling. At different times after the pumps were removed, the tumors were pulse
      labeled with iododeoxyuridine (IdUrd) and harvested 6 h later. A 3-color flow
      cytometry assay was used to simultaneously and independently analyze CldUrd and
      IdUrd incorporation, as well as DNA content. The Q-->P cells were identified as
      having only been labeled with IdUrd. The length of their S-phase was calculated
      from the movement of the Q-->P cells during the 6 h after IdUrd labeling. The
      results showed the length of S-phase for the recruited cells to be slightly, but
      significantly, longer than the length of S-phase for the total cells (11 h versus
      9 h, respectively). Thus, the recruited cells appear to have slightly slower
      kinetics than the proliferating cells in the absence of a perturbing stimulus
      such as radiotherapy or chemotherapy.

PMID- 8306345
TI  - Bombesin receptors in a human duodenal tumor cell line: binding properties and
      function.
AB  - The bombesin family of peptides elicit numerous biological responses in the gut,
      including stimulation of cell proliferation, and have been implicated as growth
      factors in a variety of gastrointestinal tumors. Even though these peptides and
      their receptors are distributed throughout the gastrointestinal tract, there are
      few cell lines available as model systems to study bombesin action in
      gastrointestinal cells. In this study, we have characterized functional bombesin
      receptors in a human duodenal cancer cell line, HuTu-80. The binding of [125I
      Tyr4]bombesin to intact cells at 4 degrees C reached equilibrium by 6 h.
      Scatchard analysis of [125I-Tyr4]bombesin binding showed that HuTu-80 cells
      contained a single class of high affinity binding sites (5900 +/- 1960/cell; Kd =
      80 +/- 20 pM). [125I-Tyr4]bombesin binding was inhibited by bombesin receptor
      agonists and antagonists with the following order of potencies: gastrin-releasing
      peptide (GRP) = GRP-(14-27) = bombesin > [DPhe6]bombesin(6-13)ethylamide > [Leu13
      psi-(CH2NH)Leu14]bombesin > neuromedin B. Photoaffinity cross-linking studies, in
      which N-5-azido-2-nitrobenzoyloxysuccinimide was used to covalently couple
      [125I]GRP(14-27) to cells at 4 degrees C, resulted in the specific labeling of a
      broad band with an apparent molecular mass of 66,000 daltons. Consistent with the
      presence of high affinity receptors, bombesin increased the formation of inositol
      phosphates in HuTu-80 cells in a dose-dependent manner (concentration eliciting
      half-maximal effect, 290 +/- 70 pM). However, under conditions where both insulin
      and serum increased [3H]thymidine incorporation into DNA, 10 nM bombesin had no
      effect either alone or in the presence of insulin. Bombesin also had no effect on
      colony formation by HuTu-80 cells in soft agar. Furthermore, the bombesin
      receptor antagonist, [Leu13 psi(CH2NH)Leu14]bombesin, did not inhibit
      [3H]thymidine incorporation or clonal growth either in the absence or in the
      presence of serum. Together, these results show that HuTu-80 cells contain high
      affinity bombesin receptors of the GRP subtype. These receptors are functionally
      coupled to second messenger production but do not stimulate cell proliferation.

PMID- 8306346
TI  - Reduced malignancy of ras-transformed NIH 3T3 cells expressing antisense
      osteopontin RNA.
AB  - Osteopontin (OPN) is a secreted, calcium-binding phosphoprotein that frequently
      has been associated with the transformed phenotype. To clarify the function of
      OPN in tumor cells, we designed experiments to: (a) express antisense OPN RNA in
      murine PAP2 cells (metastatic, ras-transformed NIH 3T3 cells) and (b) examine the
      effects of antisense OPN expression on the tumorigenic and metastatic properties
      of the cells. PAP2 cells were transfected with pNMH-asOPN, an inducible,
      mammalian expression vector that can generate antisense OPN RNA complementary to
      the OPN mRNA. Two clones have been identified that expressed antisense OPN RNA in
      vitro. While reduced OPN protein secretion was not detected when the cells were
      grown in vitro, the in vivo expression of antisense OPN RNA was associated with
      reduced tumorigenicity. Tumors that did arise, with greatly extended lag time,
      had lost expression of antisense OPN RNA in vivo, suggesting that antisense OPN
      RNA expression was associated with reduced tumorigenicity of these cells.

PMID- 8306347
TI  - Selective down-regulation of integrin receptors in spheroids of squamous cell
      carcinoma.
AB  - Integrin expression in squamous cell carcinomas have been reported to be down
      regulated in vivo. Because integrins are molecules whose functions include the
      reorganization of cytoskeleton in response to the surrounding extracellular
      matrix, we have examined the expression of integrins in the transformed cell line
      A431 when grown as multicellular spheroids or as monolayers. The spheroids were
      grown to sizes of approximately 100 microns and approximately 600 microns. Since
      larger A431 spheroids require epidermal growth factor for growth, we also
      investigated the effect of this growth factor on the expression of integrins in
      cells grown as monolayers or as small spheroids. Immunostaining studies using
      monoclonal antibodies specific for alpha 6, beta 1, and beta 4 subunits revealed
      a strong staining pattern in the periphery of the spheroids. The interior cells
      of the spheroids showed a moderate, positive reaction with the beta 1 antibody
      but significantly reduced from that at the periphery. Anti-alpha 2 antibody, on
      the other hand, revealed a uniform staining around the cells throughout the
      spheroids. Western blot analyses confirmed an overall diminution of alpha 6 and
      beta 1 protein levels in the spheroids compared with monolayers. Northern blot
      analyses showed that the low expression of integrin subunits alpha 6, beta 1, and
      beta 4 in spheroids was due to a reduction in mRNA transcripts. Northern blot
      analyses, however, showed no significant change in the expressions of alpha 2,
      alpha 5, or beta 5 mRNA. Conversely, the expression of alpha v was slightly
      reduced in spheroids. Epidermal growth factor increased the mRNA expression of
      alpha 2, alpha 6, beta 1, and beta 4 integrin subunits in cells grown either as
      monolayers or as spheroids whereas epidermal growth factor had no detectable
      effect on the expression of alpha v or beta 5. These results mimic the pattern of
      expression found in vivo and indicate that cell-cell contact and the
      microenvironments of cells within a spheroid regulate the expression and
      distribution of a subset of integrin molecules.

PMID- 8306348
TI  - Inhibition of the soluble and the tumor cell receptor-bound plasmin by urinary
      trypsin inhibitor and subsequent effects on tumor cell invasion and metastasis.
AB  - The present study was undertaken to determine whether highly purified human
      urinary trypsin inhibitor (UTI) efficiently inhibits the soluble and the tumor
      cell receptor-bound plasmin. The ability of plasmin inhibitors to regulate
      invasion by tumor cells which express membrane-associated plasmin was also
      examined. UTI and two other plasmin inhibitors [alpha 2-anti-plasmin (alpha 2AP)
      and alpha 2-macroglobulin (alpha 2M)] were used. alpha 2AP and alpha 2M, as well
      as UTI, rapidly inactivate the soluble plasmin that is not bound to cells.
      Experiments were performed in vitro using cultures of ovarian cancer HOC-I cells
      and gestational choriocarcinoma SMT-ccl cells. HOC-I and SMT-ccl cells had
      plasmin(ogen) on their cell surface, and the plasmin activity was detected on
      their cell surface enzymologically and immunologically. Receptor-bound plasmin
      reacted effectively with UTI and was directly inactivated by UTI. In contrast,
      receptor-bound plasmin was not inhibited by alpha 2AP and alpha 2M. Using a
      modified Boyden chamber and an artificial basement membrane, Matrigel, it was
      found that UTI, but not alpha 2AP or alpha 2M, can inhibit HOC-I and SMT-ccl
      cells invasion in vitro. Furthermore, in the experimental lung metastasis model,
      UTI inhibited the formation of lung metastasis by Lewis lung carcinoma cells. The
      inhibition of tumor cell invasion was not due to direct antitumor effects of UTI.
      These results suggest that inhibition of receptor-bound plasmin by UTI is
      associated with significantly reduced tumor cell invasiveness in vitro and with a
      decreased number of metastasis in vivo.

PMID- 8306349
TI  - Parathyroid hormone-like protein: alternative messenger RNA splicing pathways in
      human cancer cell lines.
AB  - Parathyroid hormone-like protein (PLP) is expressed in a wide variety of cancers
      and exerts diverse biological effects in addition to hypercalcemia. We studied
      the expression of the gene for PLP in cancer cell lines derived from different
      tissues that produce PLP. We used the polymerase chain reaction to evaluate the
      PLP mRNA species produced in these various cell lines by differential
      transcription initiation and alternative splicing pathways. A series of exon
      specific oligonucleotide primers that hybridize to DNA sequences adjacent to exon
      intron splice junctions throughout the PLP gene were designed. These primers were
      used to evaluate steady state levels of PLP mRNA species. Our analysis with
      promoter-specific primers demonstrated expression from all three putative
      transcription start sites of PLP, designated P1, P2, and P3. P2-initiated
      transcripts were present in all of the cell lines, whereas the presence of P1-
      and P3-initiated messages were cell line specific. Our analysis with carboxy
      terminal coding-specific primers demonstrated the utilization of the alternative
      splicing pathways that produce all three mature PLP polypeptides, PLP-139, -1
      173, and -1-141. The 1-139 mRNA species was found in all of the cell lines,
      whereas the 1-141 and 1-173 mRNA species were cell line specific. These studies
      demonstrate the prevalence of the P2-initiated mRNA and the PLP1-139 alternative
      splicing pathway in the tumor cell lines studied and suggest that other pathways
      of PLP gene expression may be regulated in a cell line-dependent manner. The
      particular form of PLP expressed by a given cell can influence its biological
      effects.

PMID- 8306350
TI  - Prenatal magnetic resonance imaging detection of a vein of Galen aneurysm.

PMID- 8306351
TI  - Lissencephaly syndromes: clinical aspects.
AB  - We report clinical and neurophysiological findings in six children (three female,
      three male) with type I lissencephaly and three children (all female) with type
      II lissencephaly (Walker-Warburg syndrome). In type I lissencephaly the diagnosis
      is based only on electroencephalographic (EEG) signs, whereas in type II
      lissencephaly the diagnosis rests on clinical signs. In type I lissencephaly the
      EEG typically shows high alpha-beta activity, which is not seen in type II
      lissencephaly.

PMID- 8306352
TI  - Clinical manifestations and evaluation of isolated lissencephaly.
AB  - Lissencephaly ("smooth brain") is a brain malformation characterized by a smooth
      cerebral surface, incomplete neuronal migration, and secondary abnormalities such
      as mental retardation, seizures, and minor facial dysmorphisms. Recent reports
      have produced evidence supporting several different causes including
      submicroscopic deletions in chromosome band 17p13.3, autosomal recessive
      inheritance, intrauterine infection, and intrauterine perfusion failure. We
      describe the clinical manifestations in seven patients with lissencephaly, and
      review pertinent studies regarding possible causes. The clinical manifestations
      were uniformly severe. All patients had severe mental retardation, hypotonia,
      often combined with spastic paralysis, and infantile spasms which did not respond
      to treatment. Most had poor growth, postnatal microcephaly, feeding problems, and
      frequent respiratory infections including pneumonia. None had other significant
      birth defects. Appropriate studies include computed tomography or magnetic
      resonance imaging (sometimes both), chromosome analysis, DNA analysis of the
      lissencephaly region on chromosome 17, electroencephalography and sometimes
      metabolic studies.

PMID- 8306353
TI  - Neuroimaging in lissencephalies.
AB  - Based on the published literature and on our own experiences in the imaging of
      lissencephalies with ultrasound (US), computed tomography (CT) and magnetic
      resonance imaging (MRI) we propose a strategy for the use of the different
      methods depending on the clinical symptoms and the age of the patient. In
      newborns and babies with suspected lissencephaly ultrasound should be used as the
      first method. If there is a cortical malformation and a more thorough examination
      seems necessary, CT can be used in type I lissencephaly. However, due to its
      excellent grey-white matter contrast MRI is the best method for imaging of
      lissencephalies. Especially in the diagnosis of type II lissencephaly, MRI is
      definitely superior to CT and US, and so it should be used in all patients with
      Walker-Warburg syndrome and other congenital muscular dystrophies as well as in
      all doubtful cases. It must always be remembered that the extent of the cortical
      dysplasias is quite variable, as is the presence of further malformations.

PMID- 8306354
TI  - Neuropathology of lissencephalies.
AB  - The neuropathological findings at autopsy in four cases of type I and three of
      type II lissencephaly are presented. Type I lissencephaly is characterized by
      agyriapachygyria with a markedly thickened cerebral cortex with four coarse
      histological layers. The normally myelinated white matter, often with neuronal
      heterotopias, is very narrow, and the gray-to-white matter ratio is inverted
      (about 4:1); there are no white-gray interdigitations. Claustrum and capsula
      extrema are absent. Ventricular dilatation is present, especially of the
      occipital horns. In the hypoplastic brain stem large olivary heterotopias can
      often be observed. Severe cerebellar malformations, obstructive hydrocephalus,
      severe eye abnormalities, and congenital muscular dystrophy are not seen.
      Clinically, type I lissencephaly presents as "isolated lissencephaly sequence" or
      as "Miller-Dieker syndrome" with characteristic facial dysmorphism. The long
      survival of 20 years achieved by one of our patients is very uncommon. Type II
      lissencephaly is characterized by widespread agyria. Usually, obstructive
      hydrocephalus is present with a thin cerebral mantle showing a slightly thickened
      cortex and a narrow, hypomyelinated white matter often with neuronal heterotopias
      (gray-to-white matter ratio about 1:1). The border between gray and white matter
      is blurred. Claustrum and capsula extrema are absent. Histologically, the cortex
      appears disorganized without layering; widespread leptomeningeal gliomesenchymal
      proliferations and glioneuronal heterotopias are present.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8306355
TI  - Fetal type II lissencephaly: a case report.
AB  - Type II lissencephaly is a rare cortical malformation associated with a number of
      clinical syndromes, including Walker-Warburg syndrome and some forms of
      congenital muscular dystrophy. The neuropathology of a 20-week fetus is described
      showing the pathogenesis of the malformation, which appears to result from
      abnormal migration of neurons through the pial-glial barrier into the
      leptomeninges.

PMID- 8306356
TI  - Experimentally induced cortical malformations in rats.
AB  - Different cortical malformations were produced in rats by a single dose of X-rays
      (200 cGy) given on different days during gestation. These include large cortical
      ectopic masses after irradiation on day 14; segmentation of the cerebral cortex
      following irradiation on days 15, 17, 19; and a four-layered "lissencephalic"
      cortex following irradiation on day 16. Other types of cortical malformation were
      produced in rats aged 0-2 days by one of the following procedures: focal cortical
      freezing, focal electrocoagulation, cortical aspiration, and focal brushing of
      the meninges with a blunt needle covered with cotton. These latter abnormalities
      include laminar necrosis of layer V, focal cortical dysplasia reminiscent of
      microgyria, status verrucosus deformis and porencephaly. Experimentally induced
      cortical malformations in rats can help to increase our understanding of normal
      and abnormal neurogenesis and organisation of the human cerebral cortex.

PMID- 8306357
TI  - Prenatal diagnosis and management of fetal hydrocephaly and lissencephaly.
AB  - Two cases of prenatal diagnosis of lissencephaly are presented in the context of
      a series of 118 cases of prenatally diagnosed hydrocephalus. Within this series
      there was one case of Walker-Warburg syndrome and another of Miller-Dieker
      syndrome. It is stressed that the cases reported here of ventriculomegaly
      diagnosed in utero show a very different outcome from those in published studies
      of fetal hydrocephalus which only deal with patients in whom the diagnosis was
      determined after birth. In those postnatal series there is a considerable
      selection bias, and the fate of the fetuses reported here was much worse than in
      postnatal series. Of the 118 fetuses 6 had fetal infections, 6 had chromosomal
      abnormalities, 26 had associated spina bifida, 64 fetuses had associated other
      anomalies, and only 28 had isolated hydrocephalus. Although it is difficult to
      determine the prognosis individually after prenatal diagnosis of
      ventriculomegaly, the data presented here may be helpful in counseling parents
      prenatally. The counseling should be performed with the collaboration of
      obstetricians, pediatricians, surgeons, and geneticists.

PMID- 8306358
TI  - Genetic factors in lissencephaly syndromes: a review.
AB  - Lissencephaly is a sign of various genetic and non-genetic conditions and a
      constant feature in the so-called lissencephaly syndromes. Type I lissencephaly
      in the Miller-Dieker syndrome (MDS) and the isolated lissencephaly sequence (ILS)
      is differentiated from type II lissencephaly in the Walker-Warburg
      (hydrocephalus, agyria, retinal dysplasia with or without encephalocele, HARD +/-
      E) syndrome and related conditions (e.g. muscle-eye-brain syndrome). In about 90%
      of patients with MDS structural defects have been confirmed in the short arm of
      chromosome 17 (p13.3), detectable by classical cytogenetic methods, fluorescence
      in situ hybridisation (FISH), or molecular genetic techniques. The identification
      of unbalanced inversions and translocations is of particular importance because
      of the risk of their recurrence, while deletions and ring chromosomes are mainly
      sporadic. Recently, submicroscopic deletions have also been reported in ILS,
      providing evidence that lissencephaly in MDS and ILS is caused by deletions of
      the same gene(s) in 17p13.3 and that MDS may be considered to be a "contiguous
      gene syndrome." Syndromes featuring lissencephaly type II (HARD +/- E and related
      conditions) are most probably autosomal-recessively inherited. Neither the
      location of the genes involved nor the nature of the mutations are known at
      present. It is also unknown whether HARD +/- E and muscle-eye-brain syndrome are
      allelic.

PMID- 8306359
TI  - Ocular findings in Walker-Warburg syndrome.
AB  - Ocular symptoms are frequently observed in Walker-Warburg (WWS) and associated
      syndromes. The majority of patients present with malformations of the anterior
      segment and severe retinal dysplasia. We report on the findings in a female
      patient with WWS who died at the age of 9 months. Major ocular findings were:
      severe iridocorneal malformation, a membrane-like structure of the lens and
      funnel-shaped retinal dysplasia. The retina presented various grades of
      differentiation with rosettes and atypical sequences of cells, e.g. ganglion
      cells intermingled between granular layers. The anterior part of the retina
      presented as a primitive homogeneous layer with a cell-free space that might be
      interpreted as the primary optic ventricle. This finding suggests that we are
      dealing with a primary dysplastic non-attachment rather than a real detachment of
      the retina in WWS. The malformation of the anterior segment was not typical of
      the Peters' anomaly, as usually described in WWS, but of Rieger's syndrome.

PMID- 8306360
TI  - Intrinsic malignant glioma of the pineal gland.
AB  - The case of a 6-year-old girl who presented with a glioblastoma multiforme
      arising from the pineal gland is reported. Most so-called gliomas of the pineal
      region originate from neighbouring structures; authentic malignant gliomas of the
      pineal itself are extremely rare. This appears to be only the second fully
      documented case reported in the world literature.

PMID- 8306361
TI  - Retrograde migration of the abdominal catheter as a complication of
      ventriculoperitoneal shunts: the fishhook sign.
AB  - Three cases of retrograde migration of the distal catheter of
      ventriculoperitoneal shunts into the subcutaneous fibrous tract of the thoracic
      wall are reported. To the authors' knowledge this is the first time that this
      complication of ventriculoperitoneal shunts has been described.

PMID- 8306362
TI  - Solitary cerebellar metastasis from Ewing's sarcoma: case report and review of
      the literature.
AB  - A rare case of Ewing's sarcoma metastatic to the cerebellum is presented.
      Neurosurgical intervention was required which played a significant role in the
      treatment of this patient. The incidence and treatment of central nervous system
      involvement from Ewing's sarcoma is reviewed and discussed.

PMID- 8306363
TI  - Long-term survival in malignant intracranial germ-cell tumors: a report of two
      cases and a review of the literature.
AB  - The authors report the successful treatment of two cases of malignant germ-cell
      tumor. A 12-year-old patient with a pineal immature teratoma and increase of
      alpha-fetoprotein serum levels was treated with total excision and cisplatin,
      vinblastine, and bleomycin (PVB) in combination given twice. One year later, he
      had a recurrence of tumor in the right occipital lobe, which was totally removed,
      and yolk sac tumor was verified. As subsequent adjuvant chemotherapy, PVB was
      given in four courses over 1.5 years, together with one course of cisplatin
      etoposide (PE) therapy. The patient is well 5 years and 9 months after the first
      operation. In the second case, a 19-year-old patient with a pineal mixed germ
      cell tumor, composed of germinoma, yolk sac tumor, and embryonal carcinoma, was
      treated with total excision, followed by four courses of PVB therapy and one of
      PE. She has done well in the 4.5 years since the initial treatment. Thus,
      aggressive extirpation of the lesion and subsequent combination chemotherapy
      using cisplatin and other multiple drugs, given in at least four courses over 1.5
      years, even if tumor markers return to within normal limits, might provide
      successful treatment for malignant germ-cell tumors.

PMID- 8306364
TI  - Osteosarcoma of the skull in a child: case report and review of the literature.
AB  - Osteosarcoma does not often affect the bones of the skull, occurring
      preferentially in the appendicular skeleton. The patient's age at onset seems to
      be later when the tumor is in the skull than in other sites. CT and MRI are at
      present the best means of establishing the extent of the tumor. Surgical removal
      of the lesion combined with polychemotherapy is the basis of treatment. We report
      a case of osteosarcoma of the skull in a child and review relevant publications.

PMID- 8306365
TI  - Cauda equina compression syndrome in a patient affected by thalassemia
      intermedia: complete regression with blood transfusion therapy.
AB  - Surgical excision followed by radiotherapy has been reported to be successful in
      the treatment of spinal cord compressions due to extramedullary hematopoiesis in
      patients affected by thalassemia. The authors report a case of cauda equina
      compression in such a patient successfully treated with repeated blood
      transfusions.

PMID- 8306366
TI  - Relationship between soluble tumor necrosis factor (TNF) receptors and TNF alpha
      during immunotherapy with interleukin-2 and/or interferon alpha.
AB  - Eleven metastatic cancer patients were studied during three different regimens of
      immunotherapy with interleukin-2 (IL-2) and/or interferon alpha (IFN alpha):
      group A received 4 days of IL-2 i.a. infusion (n = 3), group B IFN alpha s.c.
      during 5 days (n = 4), followed on day 3 by 5 days of a continuous IL-2 i.v.
      infusion, and group C had 4 days of IL-2 i.v. infusion together with s.c. IFN
      alpha on days 1 and 4 (n = 4). Soluble tumor necrosis factor receptors (sTNFR)
      p55 and p75 and TNF alpha concentrations in serum were analyzed before therapy
      and daily during 8 days of the first therapy cycle. sTNFR was measured by
      radioimmunoassay. sTNFR p55 increased in all patient groups from a baseline value
      of 5.2 +/- 0.9 ng/ml to a maximum of 13.6 +/- 1.2 ng/ml by days 3-4 (P = 0.003).
      sTNFR p75 increased from 7.6 +/- 1.1 ng/ml to peak values of 30.1 +/- 2.6 ng/ml
      in groups A and B (P = 0.02). In group C the sTNFR p75 response was weak (NS). In
      group B, the increase of both p55 and p75 occurred only after addition of IL-2 to
      IFN alpha. TNF alpha increased weakly during treatment with IFN alpha alone
      (group B); it rose strongly during IL-2 and the combined treatment (groups A-C)
      from 8 +/- 2 pg/ml to 115 +/- 13 pg/ml (P = 0.003). In group B, it reached the
      maximum 24 h after addition of IL-2 to IFN alpha and decreased thereafter. There
      was a significant relationship between TNF alpha and sTNFR p55 or sTNFR p75 in
      groups A and C, (P = 0.001), but not in group B. Group C was also investigated
      during the third therapy cycle. The increase of sTNFR p75 was stronger (P = 0.01)
      and that of TNF alpha weaker than in the first cycle; the sTNFR p55 response was
      similar in both cycles. In conclusion sTNFR p55 and p75 are rapidly induced
      during IL-2 and IL-2+ IFN alpha treatment, the increase of sTNF receptors
      parallels or exceeds that of TNF alpha and may influence the immunomodulatory
      effects of TNF alpha during cytokine therapy.

PMID- 8306367
TI  - Immune function of patients receiving recombinant human interleukin-6 (IL-6) in a
      phase I clinical study: induction of C-reactive protein and IgE and inhibition of
      natural killer and lymphokine-activated killer cell activity.
AB  - Interleukin-6 (IL-6) is a cytokine that acts on a variety of cell types,
      including myeloid progenitor cells and B and T lymphocytes. It has been found to
      activate cytotoxic T cells and natural killer (NK) cells and to induce T-cell
      mediated antitumour effects in animal models. In a phase I clinical trial of
      recombinant human IL-6, 20 patients with advanced cancer were entered to receive
      daily subcutaneous injections of IL-6 over 7 days followed by a 2-week
      observation period and another 4 weeks of daily IL-6 injections. Doses varied
      between 0.5 microgram/kg and 20 micrograms/kg body weight and immune functions
      were monitored throughout. At all dose levels IL-6 administration led to a marked
      increase in serum levels of C-reactive protein and a moderate rise in complement
      factor C3. The proportions of CD4, CD8 or HLA-DR lymphocytes in peripheral blood
      did not alter with IL-6 treatment nor did the in vitro proliferation of
      peripheral blood mononuclear cells induced by either phytohaemagglutinin,
      pokeweed mitogen or fixed Staphylococcus aureus. By contrast, NK cell activity,
      lymphokine-activated killer (LAK) cell activity and proliferation induced by in
      vitro culture with interleukin-2 (IL-2) were suppressed at doses exceeding 2.5
      micrograms/kg. Serum IgE levels were consistently elevated over the IL-6 dose
      range but IgM, IgG and IgA levels were unaffected. In summary there is a dose
      dependent induction of acute-phase proteins by in vivo IL-6 treatment. At higher
      IL-6 doses there is a suppressive effect on NK and LAK activity measured in
      vitro. IL-6 may thus be useful in combination cytokine therapies that seek to
      suppress LAK and favour cytotoxic T lymphocyte responses. The rise in IgE levels
      in response to IL-6 was unexpected and suggests a more pivotal role than
      previously known for the control of IgE production; this could include IgE
      related diseases.

PMID- 8306368
TI  - Growth inhibition of a colonic adenocarcinoma cell line (HT29) by T cells
      specific for mutant p21 ras.
AB  - Mutations at codons 12, 13 or 61 of the ras proto-oncogenes are found in
      adenocarcinomas of the colon and rectum. Mutated ras encode tumor-specific
      proteins, and can elicit CD4+ HLA-class-II-restricted T cell responses both in
      mouse and man. The function of such T cells is, however, unclear. In a model
      system, we investigated whether HLA-class-II restricted CD4+ T cells, specific
      for a particular peptide derived from mutant p21 ras (Gln61-->Leu), might inhibit
      the growth of a colonic cancer cell line, when it was cultured in the presence of
      the corresponding peptide. We found in this case that the growth of the colonic
      adenocarcinoma cell line HT29, when also induced to express HLA class II
      molecules by interferon gamma treatment, was inhibited. The inhibition was
      peptide-specific and required the presence of HLA-DQ8 molecules on the target
      cell. However, HLA-DQ8-expressing HT29 cells functioned poorly as antigen
      presenting cells and could only induce a weak proliferative T cell response in
      the presence of interleukin-2. The results suggest that colonic cancer cells
      expressing peptides derived from mutant p21 ras protein in a complex with HLA
      class II molecules may be a target for tumor-specific T cells. The results also
      indicate, however, that an initiation of the immune response will require
      "professional" antigen-presenting cells.

PMID- 8306369
TI  - Idiotypic antibody immunotherapy of cancer.

PMID- 8306372
TI  - [HLA-DR antigens and leukemias].
AB  - In 79 leukaemic subjects (42 with acute leukaemia, 37 with chronic myelosis) the
      authors assessed HLA-DR antigens 1-5.7 and their frequency. As compared with a
      group of 130 healthy subjects, no significant difference was found. The results
      do not support a possible relationship of HLA-DR antigens and leukaemia.

PMID- 8306370
TI  - 7-Allyl-8-oxoguanosine (loxoribine) inhibits the metastasis of B16 melanoma cells
      and has adjuvant activity in mice immunized with a B16 tumor vaccine.
AB  - We have shown previously that loxoribine exhibits adjuvant activity for B cells,
      activates natural killer (NK) cells, and enhances the activation of lymphokine
      activated killer cells by interleukin-2 (IL-2). In this study, we examined
      loxoribine for protective effects in a B16 melanoma lung tumor metastasis model.
      Significant inhibition of B16 metastasis was seen in mice given a single
      injection of 2 mg loxoribine as late as day 3 of tumor growth but the greatest
      inhibition (96%) was seen in mice given four injections of loxoribine on
      alternate days starting the day before tumor injection. In experiments in which
      both IL-2 and loxoribine were administered, both agents were active when tested
      alone, but the combination of IL-2 and loxoribine gave significantly greater
      inhibition of metastasis. Loxoribine partially inhibited the development of
      tumors in mice that had been depleted of NK cells by the administration of anti
      asialo-GM1 or anti-NK1.1 antibodies and in NK-deficient beige mice. In all cases,
      protection was seen only when smaller tumor inocula were injected. Taken
      together, these data suggest that both NK and non-NK cell populations or effector
      mechanisms with antitumor activity were activated by loxoribine. Since
      substituted guanosine analogs have been shown to have adjuvant activity in B cell
      systems, we evaluated whether loxoribine was active as an adjuvant in a tumor
      protection model. Mice immunized with both irradiated tumor cells and loxoribine
      developed a significantly lower number of lung tumors when challenged by live B16
      tumor cells, whereas mice injected with either vaccine or loxoribine alone were
      not protected. There was a clear dose response seen with both loxoribine and the
      vaccine preparations. These data suggest that loxoribine may be useful in tumor
      therapy as an immunomodulator or as an adjuvant for use with tumor vaccines.

PMID- 8306371
TI  - Internalization of an intact doxorubicin immunoconjugate.
AB  - An immunoconjugate between doxorubicin and anti-(carcinoembryonic antigen) (CEA)
      was prepared by using aminodextran (M(r) = 40,000) as the intermediate carrier,
      and the carbohydrate moiety of the antibody as the linking site. The resulting
      immunoconjugate was subjected to an in vitro evaluation for the internalization
      on the target cells (Lo Vo), and compared to that of unconjugated antibody, as
      well as the cellular uptake of unconjugated doxorubicin. The internalization was
      evaluated microscopically by following the translocation of the red fluorescence
      of doxorubicin and the green fluorescence of the fluorescein-isothiocyanate
      labeled goat anti-(mouse Ig) antibody, which visualizes the location of the
      primary mouse antibody. Anti-CEA monoclonal antibody (NP-4) was found to
      internalize into Lo Vo cells. The immunoconjugate made with this antibody was
      similarly internalized, and the doxorubicin was found to distribute with the
      primary antibody. The cell surface and cytoplasm were the major compartments of
      their distribution. These results indicate that the drug molecules were indeed
      delivered into the cells by the antibody as an intact conjugate. Unconjugated
      doxorubicin, on the contrary, was quickly absorbed by the cells and concentrated
      in the nucleus within 30 min, and never showed a distribution in the cytoplasm or
      cell membrane as in the nucleus by this procedure. The intermediate drug
      conjugate, doxorubicin-dextran, did not show internalization. The internalization
      of NP-4 antibody (or the doxorubicin conjugate) was also confirmed by studying
      the intracellular catabolism of the cell-bound antibody (or conjugate). The
      release of the degraded antibody by the cells, as differentiated by
      trichloroacetic acid precipitation techniques, was considered an indication of
      internalization. Lysosomes were involved in the degradation, since the process
      was markedly inhibited in the presence of the lysosomal enzyme inhibitor,
      ammonium chloride.

PMID- 8306373
TI  - [Treatment of oropharyngeal and esophageal mycoses in immunodeficient patients
      with fluconazole (Diflucan, Pfizer)].
AB  - Thirteen patients with oropharyngeal and oesophageal mycosis were treated with a
      new triazole antimycotic, fluconazole. In the whole group in addition to the
      basic neoplastic disease as multifactorial predisposition to mycotic infection
      was revealed. After treatment a 100% clinical as well a laboratory effect was
      achieved. However, within one month a relapse developed in three of eight
      patients and reinfection in four of eight (renewal of laboratory evidence). The
      preparation was well tolerated by the patients, no laboratory signs of organ
      toxicity were revealed. In patients with cumulation of predisposing factors for
      mycotic infection the authors recommend long-term prophylactic protection with a
      small dose of fluconazole.

PMID- 8306374
TI  - [Health and exercise].

PMID- 8306375
TI  - [Principles of general and specialized physical activity].
AB  - Physical activity plays an important role in the maintenance of functions and the
      milieu interieur. There are many types and intensities of physical activity and
      their impact on the organism and its parts is varied. However, exercise must
      always be consistent with the state of the organism at a given moment. Inadequacy
      of the form and type of physical activity becomes always manifest after different
      time intervals, as a process of maladaptation and finally as a pathological
      adaptation. It is important for every age group and every health status but
      differs markedly as regards quality and quantity. Objective evaluation of the
      load and state of the organism and capacity of a physiological response is one of
      the basic principles of prevention as well as therapy.

PMID- 8306376
TI  - [The cardiorespiratory and metabolic response in diabetics to physical loading in
      the laboratory and under field conditions].
AB  - The authors investigated and compared the response of 26 men with insulin
      dependent diabetes mellitus to a physical load in the laboratory (bicycle
      spiroergometry with a work load graded up to a maximum) and recommended 20 min.
      walking or running under field conditions (constant speed beneath the "anaerobic
      threshold"). The mean maximal oxygen uptake per minute in the laboratory (2.81 +/
      0.47 l) was insignificantly lower than reference values and combined with the
      maximal minute heart rate (mean 175 +/- 17) very variable. During the load under
      field conditions the oxygen uptake practically did not change (1.64 +/- 0.59
      l/min.) but the heart rate increased due to the declining stroke volume. The
      blood sugar level in the laboratory and during field exercise declined
      significantly. In the laboratory the base deficit and lactacidaemia increased
      markedly; under field conditions their concentration increased slightly and did
      not pass the anaerobic threshold level. The pyruvate, acetoacetate and beta-OH
      butyrate concentrations did not change much and were consistent with the response
      of well controlled diabetic patients.

PMID- 8306377
TI  - [J. E. Purkinje and sports medicine].
AB  - Work which preceded contemporary sports medicine remains in the shadow of major
      discoveries made by J. E. Purkyne. The author draws therefore attention to some
      of Purkyne's original ideas and methods which quite rightly can be considered the
      basis of sports medicine. Purkyne was probably the first who followed up the
      response to exercise manifested in the circulation and other functions of the
      organism. He was also the author of some examination procedures which together
      with modern laboratory technique are the basis of functional diagnosis. In
      Purkyne's work we find also suggestions for the solution of problems of
      prevention, so frequently discussed nowadays. He considered advisable physical
      exercise an integral part of the perspective of good health of man. It is
      remarkable how much foresight he had more than 150 years ago not only in theory
      but also from the practical aspect as regards the lifestyle of modern man.

PMID- 8306378
TI  - [Determination of beta 2-microglobulin in the serum and cerebrospinal fluid using
      radial immunodiffusion (comparison with the Elisa Pharmacia method)].
AB  - The authors elaborated a method of radial immunodiffusion for assessment of beta
      2-microglobulin serum and cerebrospinal fluid levels in patients. The method is
      based on a modified procedure of staining and decolouration. The antibody
      produced by USOL Co. which was used for the purpose was not modified. Comparison
      of 90 sera and 27 cerebrospinal fluid samples where also the reference method
      ELISA Pharmacia was used revealed almost absolute agreement, the correlation
      coefficient was 0.98. The method is used for clinical monitoring in patients with
      myelomas and renal insufficiencies.

PMID- 8306379
TI  - [Carcinoma in non-specific inflammatory intestinal diseases-- epidemiology,
      clinical aspects, dispensarization].
AB  - Idiopathic proctocolitis and Crohn's disease are important precancerous
      conditions in particular in patients with the onset of the disease at a young
      age. The causes of colorectal carcinoma in these diseases remain hypothetical.
      The risk must not be underrated but it is not high enough to justify prophylactic
      colectomy. The fundamental contribution to dispensary programmes was the
      discovery of dysplasia, i. e. precancerous changes of the intestinal epithelia.
      The main method of dispensarization is coloscopy with multiple biopsies of
      different segments of the colon and rectum. It is recommended to initiate
      dispensary programmes 10 years after the onset of the disease. Dysplasia is not
      an ideal marker of the increased risk of carcinoma and other indicators of
      malignant transformation in intestinal biopsies are intensely sought. The further
      development of dispensary programmes depends on these efforts and the results of
      cost-benefit analyses.

PMID- 8306380
TI  - [Diagnosis and therapy of cholestasis].
AB  - The submitted paper is a contribution to the problem of cholestasis from the
      aspect of contemporary knowledge recorded in the literature as well as the
      author's experience assembled in a hepatological department. The author expands
      on individual steps of the diagnostic procedure--is it a case of cholestasis?
      What type of cholestasis? The most frequent causes of intrahepatic cholestasis
      are discussed. The main point is a summary of therapeutic possibilities, in
      particular in chronic forms of cholestasis. The author emphasizes that dietary
      provisions are always essential, a as well as treatment of itching, malabsorption
      and prevention of the development of osseous changes. Drugs which are considered
      specific therapy are mentioned and their effect and side-effects are briefly
      evaluated. It appears that ursodeoxycholic acid is most promising. In the
      terminal stage under local conditions treatment is symptomatic in future we may
      be able to ensure liver transplantations which are indicated in chronic
      cholestasis.

PMID- 8306381
TI  - [Carotid artery and femoral artery disease in asymptomatic patients with various
      types of hyperlipoproteinemias and in healthy persons].
AB  - The authors examined by means of the sonograph Siemens Quantum 2000 the carotid
      and femoral arteries of 21 controls and 91 asymptomatic subjects with different
      types of hyperlipoproteinaemia (HLP). 46 patients suffered from familial
      hypercholesterolaemia, another 19 patients with hypercholesterolaemia suffered
      from ischaemic heart disease, 21 patients had familial combined
      hyperlipoproteinaemia and 5 patients had familial dysbetalipoproteinaemia. In the
      controls no plaques or stenoses were detected. In the different groups with HLP
      plaques and stenoses on the carotid artery were found in 15-36%, on the femoral
      artery in 24-63%. In patients with HLP on the common carotid artery in different
      groups a detectable intima was found more frequently, a statistically highly
      significantly wider intima (0.73 +/- 0.17 mm to 0.84 +/- 0.31 mm) and a lower
      maximum rate (79 +/- 18 cm/s to 98 +/- 24 cm/s) than in controls (0.41 +/- 0.14
      mm and 121 +/- 30 cm/s resp.). On the common carotid the authors found a
      significant direct correlation between age and the cholesterol level and between
      age and the width of the intima and an indirect correlation between age and the
      maximal rate. The differences in the width of the intima and maximum rate were
      preserved even when the groups were adjusted for age. Changes of the femoral
      artery were less marked.

PMID- 8306382
TI  - Knowledge and attitudes on AIDS relevant for the establishment of community care
      in the city of Harare.
AB  - Part I: Because of the increasing number of people with the HIV infection or
      AIDS, health resources and facilities are becoming over burdened. Many projects
      are looking towards involving communities more in caring and supporting those
      living with HIV/AIDS. In view of this, features of knowledge and attitudes have
      been drawn out of a main study on knowledge, attitudes and practices on 2 109
      respondents in the City of Harare, to demonstrate areas where urgent preparation
      is needed to facilitate community care. The majority of respondents (96 pc) were
      aware that AIDS is a sexually transmitted disease. About 70 pc of the respondents
      thought that there were many people infected with HIV in Zimbabwe. Most of the
      respondents (83.3 pc) were frightened by the idea of catching AIDS. However, 82
      pc would want to know if they are infected with the AIDS virus. About nine pc of
      the respondents said that they would commit suicide on discovering that they had
      HIV. Only 10 pc would have another child after becoming infected. A quarter of
      the respondents would not be supportive of people with AIDS. They stated that
      they would evict lodgers with AIDS, would avoid either neighbour, coworker or
      school mate with AIDS. People were generally more willing to look after their own
      children (76 pc) and less supportive of other relatives (68 pc) who had AIDS.
      Gender differences are also highlighted.

PMID- 8306383
TI  - Traumatic finger amputations in Bulawayo.
AB  - A prospective study of 20 patients with traumatic amputations of the fingers and
      a thumb was carried out during a six week period at Mpilo Central Hospital,
      Bulawayo. Most of the adult injuries (17 patients) resulted from industrial
      accidents (76.5 pc) while two out the three children sustained their injury from
      domestic accidents. Inadequate safety precaution, ignorance and human error
      contributed significantly to the injuries. Safety education and preventive
      measures both at home and in industry should be inoculated into the daily life of
      individuals.

PMID- 8306384
TI  - Antifertility effects of cowpeas on male rats.
AB  - Cowpeas (Vigna unguiculata) were fed to rats from weaning to 250 days. At the end
      of feeding trial and mating trials, histological studies were done on testicular
      and epididymal tissues. Out of the 10 rats from the cowpea fed group, only six
      had fertile matings. The average litter size for control rats was 13.7 +/- 1.0,
      while for the cowpea fed group it was 8.2 +/- 7.0. Histological studies showed
      severe degenerative changes in the testis and the presence of multinucleated
      giant cells (MGCs) in the epididymis of the cowpea fed group, that did not have
      fertile matings. It is proposed that cowpeas may contain some factors that could
      have antifertility effects, although the nature of such factors was not the
      object of this study.

PMID- 8306385
TI  - Skin irritant and tumour promoting extract from the latex of Euphorbia bougheii.
AB  - A crude ethylacetate extract was isolated from Euphorbia bougheii by a
      combination of solvent-solvent and chromatographic methods. The extract exhibited
      significant skin irritant activity on the mouse ear as well as a tumour promoting
      activity on the mouse back skin. This indicates that the use of this plant as a
      medicine must be discouraged since the latex extract causes cancer.

PMID- 8306386
TI  - Gout: an experience from Zimbabwe.
AB  - Twenty three patients with gout treated and followed up in Zimbabwe over a five
      year period were analysed. Men were afflicted 6.7 times more than women. Their
      mean age at diagnosis was 44 +/- 8 years and the mean serum uric acid level was
      588 +/- 138 mumol/l. The disease was diagnosed late with 30.4 pc of all patients
      presenting with tophi. Associated alcohol excess was universal and the shoulder,
      a proximal big joint, was also affected in 21.7 pc of all patients. There is a
      need for serum uric acid levels for the different localities in Africa to be
      mapped out and alcohol excess to be curtailed.

PMID- 8306387
TI  - Estimating child mortality in Zimbabwe: results of a pilot study using the
      preceding births technique.
AB  - Using the preceding birth technique, 2,229 mothers were interviewed at four
      antenatal centres (two of which were urban) over a three month period during a
      pilot study in Zimbabwe. Results of the study showed that there was a small
      difference between the under two and under five mortality. The smaller than
      expected difference could have been due to some degree of urbanisation being
      experienced at two of the centres, and to a systematic selection bias of the
      method. Other findings of the study showed that younger mothers (under 20 years
      of age) and older mothers (over 40 years) experienced higher proportions of
      mortality, than mothers in the age group between. The higher proportion of male
      mortality compared to that for females reflected the expected trend, but the size
      of the difference was somewhat surprising, and could have been due to recall
      bias. The mean birth interval was 36 months, rather than the expected 30 months,
      and analysis of mortality in relation to birth interval and maternal age showed
      that a birth interval of less than 18 months was associated with higher child
      mortality, significantly so with the second last child, independent of mother's
      age. Longer birth intervals (more than three years) among older mothers were
      associated with higher changes of child survival. It is concluded that the Brass
      Macrae method is a useful technique to analyse levels and trends of child
      mortality.

PMID- 8306388
TI  - Immediate bone replacement in compound depressed skull fractures.
AB  - Twelve patients with compound depressed skull fractures whose post-debridement
      cranial defects were treated with immediate bone replacement (IBR) are described.
      All were fully conscious on admission and except one who had debridement two days
      after injury, all had surgery within 24 hours of wounding. None had post
      operative wound infection or osteomyelitis of the replaced bone fragment. Four
      patients with severe or moderately severe head wounds had the comminuted free
      fragments removed without replacement. Primary repair of skull defects with bone
      fragments is recommended as the treatment of choice during debridement of
      compound depressed skull fractures of mild to moderate severity which present in
      hospital within 24 hours of injury.

PMID- 8306389
TI  - Electron microscopic observations on the luminal contents of rat epididymis
      induced by cowpeas.
AB  - The ultrastructure of tubular inclusions of caput epididymis were studied in rats
      after feeding them with cowpeas alone, from weaning (20-22 days old) to 250 days.
      The results showed cellular inclusions of various types in the caput of
      experimental rats amid sperm clumps, and epithelial damage. The experimental
      tubules showed cytoplasmic droplets and trapped flagella at various stages of
      disintegration. Other inclusions included concentric membranous bodies,
      macrophages, coalesced disintegrated spermatids, and membrane-bound amorphous
      bodies. It is proposed that these changes might be due to an altered immune
      response induced by lectins, one of the anti-nutritional factors found in
      cowpeas, which causes epididymal dysfunction and possibly renders these animals
      infertile.

PMID- 8306390
TI  - Wrapping mesh for haemostasis in severe hepatic injury.
AB  - All the time, it can not be easy to achieve for haemostasis in liver injuries.
      Surgical techniques known may fail in major hepatic traumas. This study was
      performed on nine mongrel dogs to investigate the effectiveness of mesh wrapping
      technique in severe hepatic injuries. Before surgery, cefotaxime 2 g/day was
      administered for five days. Anaesthesia was induced with 30 mg/kg thiopental
      sodium. During the operation, six dogs underwent uniform deep stellate injuries
      with a haemostatic forceps, three dogs received blunt injuries with a surgical
      hammer, and finger fracture technique was used to produce injuries in the right
      lobes of the livers. Then total wrap technique was performed with a cotton mesh
      graft. All dogs survived. This high survival rate shows that, total wrap
      technique is effective for haemostasis of severe hepatic injuries.

PMID- 8306391
TI  - Prevalence of hepatitis B surface antigen (HBsAg) among apparently healthy human
      adults seen at the Central Public Health Laboratory, Yaba, Lagos.

PMID- 8306392
TI  - A review of the effects of shear and interfacial phenomena on cell viability.
AB  - The shear sensitivity of animal and plant cells is a problem often encountered in
      large-scale cell culture. Such sensitivity varies with different cell lines and
      the severity of cellular damage may depend on both the magnitude and the duration
      of the shear stress. In a bioreactor, the shear susceptibility of cells depends
      on their response to hydrodynamic forces arising from fluid motions of particular
      scale. Cell damage may be induced by forces in the bulk liquid phase, but fluid
      motions associated with the gas-liquid interface are especially energetic. The
      detrimental effects of hydrodynamic forces are abated by the addition of some
      polymers, such as Pluronic F-68, methylcellulose, or serum; the exact mechanisms
      of protection are the subject of current research.

PMID- 8306393
TI  - [In vitro activity of chemotherapeutic agents on the most common bacterial agents
      causing urinary infections].
AB  - The authors made an investigation of the contemporary position as regards the
      effectiveness of chemotherapeutic agents used for treatment of infections of the
      urinary pathways caused by the most frequently found infectious agents in out
      patients, small Prague hospitals and the University hospital in Prague-Motol. The
      dominating infectious agent causing urinary infections remains E. coli. A serious
      feature is the increase of enterococcal infections in hospitals. As to the
      antibacterial effect, a dominant position is held by furantoin, in enterococcal
      infections in hospitals. high antibacterial activity of fluoroquinolones is,
      however, also associated with the responsibility to use them rationally.

PMID- 8306394
TI  - [Detection of Rhodococcus equi antibodies in human serum].
AB  - The authors investigated in sera of patients with pneumonia the presence of
      antibodies against the equi factor Rhodococcus equi. For examination they used
      agar immunodiffusion and a test for neutralizing the equi factor. Some 110 sera
      of different donors were examined. In agar immunodiffusion they used the equi
      factor as antigen either in the separated form or equi factor produced by the
      growing strain of R. equi. The neutralization test was implemented on agar media
      with red blood cells sensitized with staphylococcal beta-haemolysin. In all
      serological tests 27 sera reacted positively only by precipitation 30 sera, while
      53 sera did not contain antibodies against the equi factor. The authors discuss
      the impact of the assembled results and the possible participation of R. equi in
      human disease.

PMID- 8306395
TI  - [Serologic detection of B19 parvoviruses].

PMID- 8306396
TI  - [Increased incidence of invasive meningococcal disease caused by C:2a:P1.2
      meningococci in certain regions of the Czech Republic].
AB  - In the first half of 1993 an increased incidence of invasive meningococcal
      disease was recorded in the Czech Republic. In the CR a total of 59 cases were
      revealed, incl. 10 fatal ones. This high lethality (16.9%) is markedly higher
      than that from 036 recorded in this country during previous years. The highest
      incidence and death rate was recorded in the North Moravian region and in the age
      group from 15-19 years. Based on active surveillance of the invasive
      meningococcal disease by epidemiologists, microbiologists and infectiologists of
      the entire Czech Republic, it may be concluded that the sulphonamide sensitive
      strain Neisseria meningitidis C:2a:P1.2 caused in the North Moravian region a
      local epidemic of invasive meningococcal disease in the army and civilian
      population. In other regions of the CR the epidemiological situation in the first
      half of 1993 did not differ from the previous period: sporadic incidence of
      meningococcal disease, prevalence of the serological group B, highest incidence
      in the youngest age groups. The meningococcus C:2a:P1.2 was not detected in the
      CR before 1993. This uncommon epidemiological situation was resolved by
      immunization, aimed from the antigenic aspect and with regard to age and
      locality.

PMID- 8306397
TI  - [Use of diffusion methods in the determination of sensitivity of medically
      important micromycetes].
AB  - The authors evaluated the sensitivity of 35 strains of mycotic agents to eight
      antifungal preparations, using two methods: the diffuse disc test and the method
      of assessment of the MIC in a liquid medium. On comparison of results obtained by
      the two methods they reached the conclusion that the diffuse disc method makes
      possible only orientation as regards sensitivity and does not fully correlate
      with the results of MIC. Some strains with MIC values at the sensitivity level
      seemed resistant according to the disc test. From a total of seven agar media
      used for the disc test only two were suitable: the medium with casitone and
      Sabouraud's glucose agar. In particular on the former there were inhibition zones
      round the discs which were easiest to evaluate and which were constant at
      different incubation temperatures.

PMID- 8306398
TI  - [The IMU-LA-TEST ROTA Dot-ELISA test kit for diagnosis of rotavirus infections].
AB  - The newly developed IMU-LA-TEST ROTA Dot-ELISA kit manufactured in cooperation by
      Lachema Brno and VUVeL Brno for detection of viral proteins of the inner and
      outer capsid proved suitable for the rapid virological diagnosis of rotaviruses
      group A. The advantages of the method are that it is simple and unpretentious and
      does not require the use of a spectrophotometer. For comparison ROTA-ELISA
      Bioveta, ROTALEX Orion and PAGE were used.

PMID- 8306399
TI  - [Long-term study of natural foci of tick-borne encephalitis in the District of
      Olomouc].
AB  - The incidence of natural foci of tick-borne encephalitis in the Olomouc district
      has been characterized as general. This finding is based on analyses of results
      of earlier reports and results of serological blood tests of 397 small mammals
      from localities where probably transmission of the infection to humans occurred.
      The incidence almost corresponds to the incidence of the tick Ixodes ricinus. It
      has a long-lasting and also cumulative character; the number of reported cases
      from the main focal areas is proportional to the frequency of localities
      infestated with Ixodes ricinus ticks, assuming an approximately equal number of
      visitors in the woods of the district.

PMID- 8306400
TI  - [The ecology index, an epidemiologic marker of foci of Lyme borreliosis].
AB  - The ecological index (EI) as defined by Schulze et al. was determined in three
      localities of western Slovakia (Malacky, Podunajske Biskupice, Olichov) using the
      following criteria: suitability of the habitats for the occurrence of Ixodes
      ricinus ticks and their number, accessibility of habitat for men (I. phase);
      furthermore the abundance and infection rate of ticks (II. phase). A scoring
      procedure (point values of 1-5 for each parameter) was used to evaluate the EI of
      three localities studied. Based on obtained values it is suggested to
      differentiate foci as those with a definite (Malacky), potential (Podunajske
      Biskupice, Olichov), minimal and unprobable risk of transmission. The EI is
      considered a helpful method for assessing areas of risk for the transmission of
      Lyme borreliosis, indicating also the necessity of appropriate preventive
      measures.

PMID- 8306401
TI  - [Cysticercosis in the Czech Republic].
AB  - The authors report 10 cases of cysticercosis registered by the National Reference
      Laboratory for tissue helminthiasis. Six Czech citizens and four foreigners
      contracted the disease. Four of 6 Czech citizens were contaminated abroad. Six
      patients suffered from nervous manifestations of cysticercosis, 2 from muscular
      or subcutaneous cysticercosis and 2 patients had an asymptomatic course of the
      infection. The prerequisite of successful treatment with new anthelmintics is
      early diagnostics.

PMID- 8306402
TI  - [Domestic cats as a source of human flea infestations in towns].
AB  - During the summer and autumn periods of 1990-1992 a periodic massive incidence,
      infestation as well as parasitization of humans with flea Ctenocephalides felis
      were recorded in the basements of flat blocks in the central area of Kosice. The
      urban population of domestic cats served as a source of the infestation. The dark
      field examination of fleas for the presence of borrelias revealed negative
      results.

PMID- 8306403
TI  - [Communicable diseases and primary health care].

PMID- 8306404
TI  - [The effect of subinhibitory levels of antimicrobial agents on bacteria].
AB  - The authors reviewed data in the literature about influencing the virulence
      factors and other properties of important gram-negative and gram-positive
      bacteria by sub-MICs of antimicrobial substances. Special attention is devoted to
      influencing the exo-products as well as adherent properties of Pseudomonas
      aeruginosa.

PMID- 8306405
TI  - [Historical data on the status of bacterial sensitivity to antibiotics].

PMID- 8306406
TI  - [Dr. Vaclav Tomasek, Dr.Sc.--founder of microbiology in Brno (on the 100th
      anniversary of his birth and 30th anniversary of his death)].

PMID- 8306407
TI  - [Diagnosis, therapy and dispensarization of sexually transmitted diseases in the
      Czech Republic in the first half of 1993. Notice of a decrease in the trend of
      reporting venereal diseases].

PMID- 8306408
TI  - Nation-wide randomized comparative study of doxorubicin, vincristine and
      prednisolone combination therapy with and without L-asparaginase for adult acute
      lymphoblastic leukemia.
AB  - A randomized clinical trial of combination chemotherapy for adult acute
      lymphoblastic leukemia (ALL) with doxorubicin, vincristine and prednisolone with
      and without L-asparaginase (AdVP vs L-AdVP) was conducted, involving 58
      institutions throughout Japan. After reaching complete remission (CR), patients
      were treated with the same regimen for more than 2 years. Among 166 evaluable
      cases of the 198 cases enrolled, CR rates were 63.1% (53/84) with AdVP and 64.6%
      (53/82) with L-AdVP (P = 0.837). Median survival times and 7-year survival rates
      were 12.7 months and 21.2% with AdVP, and 16.0 months and 22.3% with L-AdVP (P =
      0.955 by generalized Wilcoxon test [GW], P = 0.952 by log-rank test [LR]). Median
      disease-free survival times and 7-year survival rates were 13.5 months and 23.8%
      with AdVP and 17.0 months and 30.6% with L-AdVP, showing some increments for L
      AdVP but no statistical significance (P = 0.141 by GW, P = 0.300 by LR). Among
      the cases of extramurally confirmed FAB subtypes, CR rates were 75.9% (63/83) for
      the L1 subtype and 51.3% (39/76) for the L2 subtype (P = 0.001). As to adverse
      effects, pancreatitis was complicated more frequently in L-AdVP than in AdVP (P =
      0.039). Other side effects such as hyperbilirubinemia, diabetes mellitus,
      diarrhea and hypofibrinogenemia were observed more frequently with L-AdVP, but
      with no statistical significance. Thus, addition of a single course of L
      asparaginase in the induction phase of combination chemotherapy with doxorubicin,
      vincristine and prednisolone did not significantly enhance the effect of
      antileukemic treatment of adult ALL.

PMID- 8306409
TI  - Postoperative chemotherapy including intraperitoneal and intradermal
      administration of the streptococcal preparation OK-432 for patients with gastric
      cancer and peritoneal dissemination: a prospective randomized study.
AB  - We studied the effects on survival time of postoperative immuno-chemotherapy,
      including the streptococcal preparation OK-432, in patients with gastric cancer
      and synchronous peritoneal dissemination. The patients were prospectively
      randomized and a valid statistical assessment could be made for 109. Patients
      randomized to group B received therapy that is widely used in Japan to treat
      patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur
      and uracil in a molar ratio of 1:4, for 1 year. Patients randomized to group A
      received the same drugs as were given to group B patients plus OK-432 i.p. for 7
      days, beginning on postoperative day 0, and OK-432 by intradermal injection for 1
      year, at 2-week intervals. There were no differences between the two groups in
      any known prognostic factor or in the dose of any drug administered except for OK
      432. There was no difference in the toxicity rate between the groups. In this
      negative trial, there was no improvement in survival time with the addition of OK
      432 to MMC and UFT for patients with gastric cancer and peritoneal dissemination.

PMID- 8306410
TI  - Laser flow cytometric studies on the intracellular accumulation of anthracyclines
      when combined with heat.
AB  - The effects of heat on intracellular accumulation of anthracyclines were
      investigated by laser flow cytometry analysis. Sarcoma-180 cells were exposed to
      Adriamycin (ADM), epirubicin (EPIR), daunomycin (DM), THP-Adriamycin (THP), ME
      2303 (ME) and KRN-8602 (KRN) at 37 degrees C and at higher temperatures. There
      was a dose-dependent increase in the fluorescence intensity of all drugs at 37
      degrees C, but heat varied the fluorescence intensity of each drug. At 43 degrees
      C the cellular fluorescence of ADM and EPIR increased by approximately 200%, but
      for DM the increase was 110-130%. The cellular fluorescence of THP and ME was
      little affected by heat, and heat reduced that of KRN to 80-90%. Each drug showed
      was unique in the relationship between drug exposure time and the fluorescence
      intensity at 37 degrees C and 43 degrees C. Cytotoxicity determined by the MTT
      assay was enhanced with heat in the cases of ADM and EPIR, but not with DM, THP,
      ME, or KRN. Thus, ADM and EPIR are expected to show enhanced antitumor activities
      when given in combination with hyperthermia.

PMID- 8306411
TI  - Lipophilic platinum complexes entrapped in liposomes: improved stability and
      preserved antitumor activity with complexes containing linear alkyl carboxylato
      leaving groups.
AB  - Lipophilic diaminocyclohexane (DACH) platinum complexes have shown significant
      promise in preclinical studies. One of these compounds, cis-bis-neodecanoato
      trans-R,R-1,2-diaminocyclohexaneplatinum++ +(II) (NDDP), which contains two
      branched leaving groups of 10 carbons, showed a favorable toxicity profile in a
      liposomal formulation in early clinical trials. However, like many other DACH
      platinum compounds with branched leaving groups, it is unstable within the
      liposomes, thus preventing its widespread clinical evaluation. We studied the
      effect of the configuration of leaving groups on intraliposomal complex stability
      by studying a series of DACH platinum complexes containing linear alkyl
      carboxylato leaving groups of 5-18 carbons. The entrapment efficiency was greater
      than 90% for all liposomal preparations of the complexes and was independent of
      lipid composition and length of the leaving group. The drug leakage from the
      liposomes was minimal, but was directly related to the length of the leaving
      group. Intraliposomal stability was inversely related to the length of the
      leaving group and the content of DMPG (dimyristoyl phosphatidylglycerol) in the
      liposomes. The effect of length of leaving group on intraliposomal stability was
      minimal in compounds with leaving groups smaller than 10 carbons, but very
      pronounced in compounds with longer leaving groups. Stable liposomal formulations
      of selected compounds with leaving groups of 6 and 10 carbons had significant in
      vivo antitumor activity against both L1210/S and L1210/PDD leukemias. The results
      indicate (1) that compounds with linear leaving groups are much more stable
      within DMPG-containing liposomes than compounds with branched leaving groups and
      (2) that DMPG is required for in vivo antitumor activity. Stable and active
      liposomal formulations of selected compounds with linear leaving groups have been
      identified. These formulations are candidates for clinical development.

PMID- 8306412
TI  - Apoptosis induced by etoposide in small-cell lung cancer cell lines.
AB  - The DNA fragmentation, a parameter of apoptosis, in non-small (NSCLC) and small
      (SCLC) cell lung cancer cell lines (N231 and PC-9) was evaluated. The DNA
      fragmentation in SCLC lines, but not in NSCLC lines, was observed in overgrown
      cells without exposure to anticancer drugs. In etoposide (VP-16)-treated N231 but
      not PC-9 cells, DNA fragmentation continued to increase up to 42 h, and the
      increase was dependent on the concentration of VP-16. The endonuclease activity
      of VP-16-treated N231, but not PC-9, cells required both Ca2+ and Mg2+ for full
      activity. It was elevated in a time- and concentration-dependent manner. As this
      activity was not affected by addition of cycloheximide, the activation of the
      endonuclease activity without protein synthesis may be involved in VP-16-induced
      cytotoxicity in N231.

PMID- 8306413
TI  - Preclinical pharmacokinetics and stability of isophosphoramide mustard.
AB  - Stability and preclinical pharmacokinetics of isophosphoramide mustard (IPM), an
      active metabolite of ifosphamide, were investigated using analytical methods
      developed in this laboratory. For stability evaluation of IPM we used a rapid,
      high-pressure liquid chromatographic (HPLC) method by which IPM is analyzed
      directly from aqueous solutions without derivatization on a 10-microns C-18
      reversed-phase column with theophylline as the internal standard. IPM in sodium
      phosphate buffers was found to undergo pH-dependent first-order degradations. At
      pH 7.4 and 38 degrees C, the IPM solution showed a half-life of 45 min. A gas
      chromatographic-mass spectrometry (GC/MS) method for the analysis of IPM in
      plasma was also developed. This method utilized solid-phase extraction with
      deuterium-labeled IPM as the internal standard. The routine detection limit for
      the assay was 50 ng/ml with within-run and between-run coefficients of variation
      of 6% and 11%, respectively. By this method, stability of IPM in plasma and in
      RPMI 1640 tissue culture medium was evaluated, and its pharmacokinetics in the
      Sprague-Dawley rat following i.v. administration at 40 mg/kg were investigated.
      IPM was found to be more stable in these media, with half-lives in the range of
      100 min. IPM plasma pharmacokinetics were found to decline monoexponentially with
      terminal half-lives ranging from 6.8 to 18.7 min and total clearance between 6.0
      and 18.3 ml/min. Plasma protein binding of IPM was found to be 55%, and the
      partition ratio between plasma and red blood cells of 4.9 to 1, respectively.
      Cytotoxicity of IPM to L1210 cells was evaluated, and the results indicated that
      the IC50 with 1-h and 4-h exposure was 33 and 15 microM, respectively. Based on
      these data, IPM plasma levels in the rat declined below the IC50 in about 1 h at
      this dose. More frequent dosing or infusion may be necessary to maintain adequate
      drug levels for antitumor activity when IPM is administered directly.

PMID- 8306414
TI  - Accumulation of HL-60 leukemia cells in G2/M and inhibition of cytokinesis caused
      by two marine compounds, bistratene A and cycloxazoline.
AB  - The effects on the cell cycle of two biologically active compounds, bistratene A
      and cycloxazoline, from the marine ascidian Lissoclinum bistratum were studied in
      HL-60 human leukemia cells using flow cytometry. Both compounds were shown to
      cause an apparent accumulation of cells in the G2/M phase. This effect was shown
      to be both time- and dose-dependent. At the longer time points (30 and 48 h after
      addition of the compounds) polyploidy was apparent. The fate of cells labeled in
      the S phase with 5-bromo-2'-deoxyuridine (BrdUrd) was analysed using a bivariate
      BrdUrd/PI (propidium iodide) technique. Bistratene A and cycloxazoline treatment
      prevented the majority of BrdUrd-labeled cells from progressing through to the G1
      phase. Approximately 50% of the cells were delayed at G2/M, and a significant
      proportion of cells appeared to be polyploid. Light and electron microscopy
      revealed the presence of multinucleated cells accounting for the apparent
      polyploidy. The progression of cells out of the G1 phase was also examined by
      synchronising cells with mimosine and releasing them from mimosine block in the
      presence of bistratene A. There was no evidence of a block at the G1/S phase
      transition or through the S phase since DNA synthesis was not inhibited. The
      mechanism by which these compounds interfere with cytokinesis is presently
      unknown but, in the case of bistratene A, may be linked to altered
      phosphorylation of cellular proteins involved in cell-cycle control.

PMID- 8306415
TI  - Induction of apoptosis in murine tumors by cyclophosphamide.
AB  - Whereas there have been several recent reports of the induction of apoptosis by
      chemotherapy agents in cell culture systems, much less is known about the role of
      this mode of cell death in tumors treated in vivo. We therefore quantitated the
      proportion of apoptotic cells induced as a function of time and dose in two
      murine tumors treated with cyclophosphamide in vivo. The two tumors were a
      mammary adenocarcinoma, MCa-4, and an ovarian adenocarcinoma, OCa-1. The percent
      apoptosis was scored from stained histological sections of the tumors using a
      system based on the characteristic features of the apoptotic nuclei. The kinetics
      of apoptosis development were determined over a 5-day period following treatment
      of the mice with 200 mg/kg. The percent apoptosis peaked between 10-18 h in both
      tumors and then slowly declined to background levels by 5 days after treatment.
      The dose responses showed that even much lower doses, 25 mg/kg, could induce
      significant apoptosis and that the proportion of apoptotic cells plateaued at
      doses higher than 100 mg/kg. These results are compared and contrasted with our
      previous reports on apoptosis induction in these same tumors with ionizing
      radiation.

PMID- 8306416
TI  - Randomized clinical trial of mitomycin-C with or without pretreatment with WR
      2721 in patients with advanced colorectal cancer.
AB  - The use of mitomycin for metastatic colorectal cancer has been limited by
      mitomycin's myelosuppressive potential. The objective of this randomized study
      was to determine whether WR-2721 would decrease the hematologic toxicity of
      mitomycin in patients with colorectal cancer resistant to fluorouracil-based
      therapy. Ninety-seven patients with refractory colorectal cancer were randomized
      to receive either mitomycin 20 mg/m2 only or the same dose of mitomycin after
      pretreatment with WR-2721, 910 mg/m2. The principal toxicity in both groups was
      thrombocytopenia. The platelet nadirs were lower in patients receiving single
      agent mitomycin (P = 0.026). Surprisingly, no clinical complete or partial
      responses were noted in either group, and survival was not different between the
      two groups. Thus, while WR-2721 decreased the thrombocytopenia associated with
      mitomycin therapy, mitomycin was ineffective in the treatment of refractory
      colorectal carcinoma.

PMID- 8306417
TI  - Pharmacokinetics of high-dose methotrexate in adult osteogenic sarcoma.
AB  - The pharmacokinetics of 222 infusions of high-dose methotrexate (MTX) with
      leucovorin rescue were studied in 22 adults with osteosarcoma. To reduce the
      variability of plasma concentration, we individualized dose regimens using a
      Bayesian method to reach a concentration of 10(-3) M MTX at the end of an 8-h
      infusion. The mean concentration observed at the end of the infusion was 1016 +/-
      143 mumol/l. The mean dose delivered was 13.2 +/- 2 g/m2. The clearance was 49.1
      +/- 11.7 ml min-1 m-2. The decay of the plasma concentration of MTX after
      completion of the infusion followed a two-compartment model with a t1/2 alpha of
      2.66 +/- 0.82 h and a t1/2 beta of 15.69 +/- 8.63 h. The volume of distribution
      was 0.32 +/- 0.08 l/kg. As compared with previously published data, the
      interindividual and intraindividual variations in the concentration at the end of
      the infusion were reduced, with values of 14% and 5.9%-21%, respectively, being
      obtained. Severe toxicities were avoided, and there were only 3 hematologic and 8
      digestive grade 3 side effects and no grade 4 complication. The t1/2 alpha and
      the MTX plasma concentrations at 23 and 47 h were correlated with renal toxicity
      (P < 0.001). However, no correlation was found between the pharmacokinetic
      parameters and other signs of toxicity. There was no significant difference in
      pharmacokinetics between the toxic and nontoxic groups. In the same manner, the
      parameters of the group of patients sensitive to MTX were not statistically
      significant different from those of the group of nonsensitive patients.

PMID- 8306418
TI  - Plasma pharmacokinetics, tissue disposition, excretion and metabolism of
      vinleucinol in mice as determined by high-performance liquid chromatography.
AB  - We investigated the pharmacokinetics of the experimental semisynthetic vinca
      alkaloid vinleucinol (VileE; O4-deacetyl-3-de(methoxycarbonyl)-3-[[[1
      ethoxycarbonyl-2- methylbutyl]amino]carbonyl]-vincaleukoblastine). The study was
      performed in male FVB mice receiving 10.5 mg/kg VileE i.v. or p.o. Plasma, urine,
      faeces and tissue samples were analysed by a selective method based on ion
      exchange normal-phase high-performance liquid chromatography (HPLC) with
      fluorescence detection and liquid-liquid extraction for sample clean-up. Apart
      from the parent drug, two other metabolic compounds were detected. One of these
      metabolites is vinleucinol acid (VileA; O4-deacetyl-3-de(methoxycarbonyl)-3-[[[1
      carboxyl-2- methylbutyl]amino]carbonyl]-vincaleukoblastine), which possesses no
      cytotoxic activity. The structure proposed for the second metabolite (VileX) was
      based on tandem mass spectrometry (MS-MS) and infrared (IR) spectroscopy data.
      Metabolization of VileE to VileX must occur in the amino acid moiety of the
      molecule, with a (beta- or gamma-) lactone ring being formed after oxidation of
      the (beta- or gamma) carbon of the amino acid. VileX is a major metabolite, which
      is excreted in faeces and urine after i.v. administration and accounting for up
      to 23% of the administered dose. The activity of VileX against cultured L1210
      cells is four times that of the parent drug VileE and comparable with that of
      vinblastine (VBL). At 48 h after administration of VileE, the concentration of
      VileX exceeds that of the parent drug in many tissues. These findings indicate
      that the metabolite VileX may be at least largely responsible for the activity
      observed against xenografts in mice after administration of the parent drug,
      VileE.

PMID- 8306419
TI  - Unexpected radiation protection with 13-cis-retinoic acid plus interferon alpha
      2a.
AB  - A recent clinical protocol combining retinoic acid, interferon, and radiotherapy
      for advanced cervical cancer produced proctitis severe enough to necessitate dose
      reductions. In an attempt to model this biological response to multimodality
      therapy, we used a murine model to study the response of the colonic epithelium.
      Mice were treated with retinoic acid (100 micrograms/day) and interferon (3 x
      10(4) units/day) for 5 days before undergoing whole-body irradiation. The
      functional response of the bowel was assessed by the ability to maintain body
      weight, and reproductive cell survival was quantified by the colon crypt assay.
      Both assays indicated a moderate protective effect of treatment with retinoic
      acid and interferon prior to irradiation. Protection factors in the range of 1.1
      1.4 were observed.

PMID- 8306420
TI  - A phase II study of pirarubicin in patients with advanced recurrent head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: Head and neck squamous carcinoma (HNSCC) is a chemotherapy-sensitive
      tumour, but this sensitivity is not reflected in an impact on survival. The study
      of new drugs is therefore indicated. Pirarubicin (4'-O-tetrahydropyranyl
      doxorubicin) has a higher preclinical index than doxorubicin, with low
      cardiotoxicity in animal models. PATIENTS AND METHODS: Twenty-six patients with
      squamous cell carcinoma of the head and neck and documented progression after or
      during previous chemotherapy were entered into the study. Two patients were
      ineligible for evaluation. Pirarubicin was given at a dose of 70 mg/m2 every 3
      weeks. RESULTS: Partial remission was seen in 1 of the 24 evaluable patients. The
      predominant toxicity was bone marrow depression, with leucopenia in 62% of the
      patients. One patient died due to a gastrointestinal haemorrhage during a period
      with WHO grade IV thrombocytopenia. CONCLUSION: On the basis of these results,
      pirarubicin cannot be recommended as second-line treatment in patients with
      recurrent and metastatic HNSCC. Its possible relevance for first-line treatment
      cannot be judged from these data.

PMID- 8306421
TI  - Ontogeny of proenkephalin mRNA and enkephalin peptide expression in the
      cerebellar cortex of the rat: spatial and temporal patterns of expression follow
      maturational gradients in the external granular layer and in Purkinje cells.
AB  - Proenkephalin mRNA and peptide products were examined in developing cells of the
      postnatal rat cerebellar cortex using in situ hybridization and
      immunocytochemistry. On day 7, proenkephalin mRNA was first detected as discrete
      cellular labeling in Golgi cells and as a diffuse hybridization signal over the
      Purkinje cell layer. On day 14, proenkephalin mRNA and peptide products primarily
      appeared in distinct subpopulations of Purkinje cells present in the posterior
      and lateral cerebellum. Similarly, in the external granular layer (EGL),
      enkephalin immunoreactivity was present only in the posterior and lateral
      portions of the cerebellum on day 14. However, proenkephalin mRNA was not
      detected in enkephalin-immunoreactive EGL cells. On day 21, the subset of
      Purkinje cells that expressed proenkephalin mRNA and peptides were distributed
      more uniformly throughout the cerebellum. On day 28, a few enkephalin
      immunoreactive Purkinje cells were uniformly present throughout the cerebellum,
      but proenkephalin mRNA was not detected in most of these cells. The spatial
      gradients in proenkephalin mRNA expression evident in the Purkinje cells of
      younger rats were no longer present in 28-day-old rats. These findings are
      important, because endogenous opioids such as enkephalin have been previously
      shown to inhibit the growth of Purkinje cell dendrites and dendritic spines, and
      inhibit the rate of mitosis in EGL neuroblasts. Cells do not develop at uniform
      rates within the cerebellum. There are regional differences in the timing of the
      formation of the EGL, and in the morphogenesis of Purkinje cells. In conjunction
      with previous work, the present findings suggest that during development, the
      pattern of enkephalin immunoreactivity in Purkinje and EGL cells closely follows
      the spatial and temporal gradients of maturation in both these cell types. The
      emergence and disappearance of enkephalin immunoreactivity in Purkinje and EGL
      cells is spatially and temporally related, and coincides with proenkephalin mRNA
      expression in Purkinje cells. Thus, the transient and coordinated appearance of
      enkephalin in cerebellar Purkinje and EGL cells may contribute to regional
      differences in the rate of cerebellar maturation, and may help synchronize the
      developmental interactions between these two cell types.

PMID- 8306422
TI  - Expression of peptide YY and mRNA for the NPY/PYY receptor of the Y1 subtype in
      dorsal root ganglia during rat embryogenesis.
AB  - We have used in situ hybridization to study the distribution of mRNA for
      neuropeptide Y (NPY), peptide YY (PYY) and the NPY/PYY receptor of the Y1 subtype
      during ontogenesis in the rat and immunohistochemistry to analyse peptide
      immunoreactivity for NPY and PYY. We found that mRNA and immunoreactivity for NYY
      are transiently expressed in dorsal root ganglia (DRG) at embryonic day 16 (E16).
      In contrast, neither NPY mRNA nor NPY-like immunoreactivity were found in DRG at
      any developmental stage. The Y1 receptor mRNA is not expressed in DRG at E16 but
      it appears in these ganglia later in development (E20) and it is present in DRG
      of adult rats. In sagittal sections of whole embryos at very early stages of
      development we found that the onset of PYY mRNA expression is around day 11, when
      mRNA for PYY is found in the foregut. NPY and Y1-receptor mRNA are not detected
      in whole embryo sections until around day 14. Therefore, PYY mRNA expression
      precedes by 2-3 days the expression of mRNA for both NPY and the Y1 receptor. At
      E14, PYY mRNA is present in trigeminal ganglia and stomach. Our results suggest
      that PYY is not only a gut hormone but may also act as a neuropeptide with roles
      in the development of sensory neurons.

PMID- 8306423
TI  - Effects of bilirubin infusion on local cerebral glucose utilization in the
      immature rat.
AB  - The clinical features of kernicterus have been extensively described. However,
      there are still no data available on a possible correlation between the areas
      which appear to preferentially accumulate bilirubin and regional changes in
      cerebral functional activity. Therefore, we applied the quantitative
      autoradiographic [14C]2-deoxyglucose method to the measurement of local cerebral
      metabolic rates for glucose (LCMRglc) in immature rats receiving a bilirubin
      infusion. A loading dose of 160 mg/kg bilirubin in a buffered serum albumin
      solution was first given to the rats over 15 min. Thereafter, bilirubin was
      infused at a reduced rate, 64 mg/kg/h. Bilirubin infusion lasted from 2 to 3 h
      according to the age of the animal, in order to obtain a plasma concentration of
      bilirubin ranging from 200 to 300 mumol/l over the experimental period. Bilirubin
      entered the brain without any sign of blood-brain barrier alteration. The [14C]2
      deoxyglucose was injected to the animals 45 min before the end of bilirubin
      infusion. Rats were studied at 3 postnatal ages, 10 (P10), 14 (P14) and 21 days
      (P21). Hyperbilirubinemia induced widespread decreases in LCMRglc's in all brain
      areas and at all ages. These decreases were mostly prominent in sensory areas,
      auditory and visual, as well as in hypothalamic and thalamic regions. Especially
      at P10, the distribution of LCMRglc's was strikingly heterogeneous in both
      cerebral cortex and caudate nucleus, appearing as alternate dark and white
      columns or as alternate dark and light dots, respectively. The data of the
      present study are in agreement with clinical observations reporting that
      bilirubin mostly accumulates in the striatum and cranial nerves and that the
      neurological sequelae of kernicterus are very often hearing loss as well as motor
      problems.

PMID- 8306424
TI  - Graded distribution of the neural 2A10 antigen in the developing chicken retina.
AB  - During retinal histogenesis, post-mitotic cells become located in different
      tissue layers, where they differentiate into distinct cell types. In an attempt
      to elucidate mechanisms of cell differentiation, we have employed hybridoma
      technology in conjunction with various in vitro techniques. Here, we present
      monoclonal antibody 2A10, which binds specifically to the cell surface of neurons
      and outgrowing neurites. Within the retina 2A10 antigen expression is
      developmentally regulated being most pronounced during the period of tissue layer
      formation. Elevated antigen expression is limited to post-mitotic neurons as
      revealed by labeling with bromodeoxyuridine. Retinal ganglion cells, which are
      the first neurons to develop, appear not to influence the overall developmental
      regulation of the antigen in the retina, since elimination of these cells by
      virtue of optic nerve transection in ovo did not alter the antigen expression.
      The antigen is distributed in a graded fashion in the radial axis of the retina.
      Maximal immunoreactivity was found at the inner surface of the retina (optic
      fiber layer), whereas only minute reactivity was detected in the outermost layer.
      This graded distribution could possibly be involved in a topographic system
      providing positional information for differentiating neurons. Operationally, MAb
      2A10 is a useful marker for retinal neurons, and provides a tool for establishing
      pure Muller glia cultures by complement-mediated cytolysis of retinal neurons.

PMID- 8306425
TI  - Ornithine decarboxylase activity in fetal and newborn rat brain: responses to
      hypoxic and carbon monoxide hypoxia.
AB  - In response to acute maternal hypoxia, ornithine decarboxylase (ODC) activity
      increased significantly in fetal rat brain, peaking at 4 h. This was associated
      with increased ODC mRNA and elevated polyamine concentrations. To correlate this
      response with development, we measured ODC activity in the rat from gestational
      day E 17 to postnatal day P 10. We also examined to what extent hypoxia induces
      increased ODC activity in adult rat brains and whether the response to chronic
      hypoxia differed from that to acute hypoxia. To test the hypothesis that this
      increased activity is due to hypoxic hypoxia per se, we subjected pregnant dams
      to inspired carbon monoxide concentrations ranging from 150 to 1000 ppm and
      assayed ODC activity in the fetal brain 4 h later. In the fetus, ODC activity was
      elevated on E 17 in the cerebrum and cerebellum. It declined gradually to about
      one-tenth E 17 levels by E 21 and remained low thereafter except for a postnatal
      elevation in the cerebellum on P 3. In response to 10.5% O2, in the 3-day-old
      rat, ODC activity peaked between 2 and 3 h of hypoxia, increasing 3-fold in the
      hippocampus and 2-fold in cerebellum. Similar increases were seen in the hypoxic
      adult rat brain. In inspired oxygen dose-response studies, exposure of P 3 rat
      pups to 13.25% O2 for 2.5 h produced a 1.5-fold increase in ODC activity; 10.5%
      O2 produced a 2-3-fold increase while in response to 9% O2, ODC activity remained
      at baseline levels. With maternal CO-hypoxia, ODC activity increased in the fetal
      brain at 4 h, as seen with hypoxic-hypoxia. For example, in hippocampus, ODC
      activity doubled at 500 ppm and tripled at 600 ppm. We conclude: (1) apparently,
      the ability to respond thus is not lost as the animal ages and may represent an
      important cellular response to acute hypoxia; (2) the increase in hypoxic-induced
      ODC activity is relative to the already elevated activity seen from E 17 to E 20;
      a vast reserve for the induction of fetal ODC activity probably exists and may
      indicate the importance of this enzyme during this time frame for differentiation
      and growth promotion; and (3) the CO-hypoxia studies suggest that some aspects of
      the cellular responses to CO- and hypoxic-hypoxia are similar.

PMID- 8306426
TI  - Postnatal development of NADPH-diaphorase activity in the superior colliculus and
      the ventral lateral geniculate nucleus of the rat.
AB  - We have studied the postnatal development of dihydronicotinamide adenine
      dinucleotide phosphate diaphorase (NADPH-d) activity in the superior colliculus
      (SC) and the ventral lateral geniculate nucleus (LGv) of the rat. We describe two
      different developmental patterns of NADPH-diaphorase activity. The first pattern,
      observed in the deep layers of the SC, shows a transient activity during the
      first week which progressively decreases during the following two weeks. The
      second pattern is observed in the superficial layers of the SC and in the LGv.
      They become positive during the first week, their NADPH-d activity increases
      progressively during the second and third weeks, reaching the adult pattern at
      the fourth week. On the whole, the developmental chronology of the laminar
      distribution of NADPH-d in the SC displays an inside-out pattern. Our results
      suggest that NADPH-d activity may play different roles at different stages of the
      developing nervous system.

PMID- 8306427
TI  - Cytokines affecting survival and differentiation of an astrocyte progenitor cell
      line.
AB  - The effects of various cytokines on survival and differentiation of an astrocyte
      progenitor cell line (AP-16) were examined. Epidermal growth factor (EGF)
      deprivation caused death of AP-16 cells by apoptosis. Transforming growth factor
      alpha (TGF-alpha) and basic fibroblast growth factor (bFGF) prevented the
      apoptosis occurring in the absence of EGF. Leukemia inhibitory factor (LIF) and
      ciliary neurotrophic factor (CNTF) induced glial fibrillary acidic protein (GFAP)
      and decreased A2B5 antigen in AP-16 cells, indicating that these cytokines
      induced AP-16 cells to differentiate into astrocytes.

PMID- 8306428
TI  - Developmentally transient expression of acetylcholinesterase within cortical
      pyramidal neurons of the rat brain.
AB  - Using a histochemical method for the visualization of cholinesterase activity in
      neurons, we have observed developmentally transient expression of
      acetylcholinesterase (AChE) in cortical pyramidal neurons of the rat brain.
      Depending on the extent of the deposition of AChE reaction product, several types
      of cortical neurons could be visualized. We designated neurons with moderate-to
      high staining intensity as AChEH and neurons with relatively lower staining
      intensity as AChEL. At birth (P0), very little AChE activity was found within
      cortical neurons. Between P1-P4, there was a gradual emergence of AChE-stained
      cortical neurons. At this stage, the majority of these neurons were of the AChEL
      type. At P5-P7 we observed an abrupt increase in AChE-stained cortical neurons.
      The number and the staining intensity of these neurons was at a peak at P8-P10.
      At this age range, the majority of these neurons were of the AChEH variety and
      displayed morphological characteristics of cortical pyramidal neurons. At P11
      P15, there was an abrupt decrease in the number of AChEH neurons. After P15, the
      density and staining intensity of cortical AChE-positive (cholinergic) axons
      gradually increased. Nevertheless, AChEL pyramidal neurons were detected through
      these fibers up to P21. At P21, a dense plexus of AChE-positive axons was
      observed in all cortical areas while very little AChE reaction product was
      visible in pyramidal neurons, and this pattern continued into adult life. When
      the adult cortex was denervated from its AChE-positive axons by lesions of the
      nucleus basalis magnocellularis, many AChEL pyramidal neurons were
      uncovered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306429
TI  - Ontogeny of gamma-aminobutyric acid in efferent fibers to the rat cochlea.
AB  - Cochlear efferent innervation originates in two different groups of neurons
      located in the superior olivary complex. A first group of olivocochlear neurons
      (lateral efferent neurons) lies in the lateral superior olive. They send axons to
      the organ of Corti, where they synapse with radial afferent dendrites of primary
      auditory neurons, postsynaptic to the inner hair cells. The second group of
      neurons (medial efferent neurons) is found in medial subnuclei of the superior
      olivary complex and sends axons to synapse with outer hair cells. Subpopulations
      of both medial and lateral olivocochlear neurons probably use gamma-aminobutyric
      acid (GABA) as a neurotransmitter. We have used an immunoperoxidase technique to
      detect GABA-like immunoreactivity (GABA-LI) in postnatal maturing rat cochleas.
      The GABA-LI appeared in the inner hair cell region by P3 (P1 = birth) and reached
      a mature appearance by P15-P16. In the outer hair cell region, GABA-like
      immunoreactive fibers and terminals could not be identified until P9 and they
      were only found in the apical end of the cochlea. There was a dual gradient of
      maturation of GABA-LI in the cochlea. The GABA-LI appeared first at the cochlear
      base and then extended towards the apex. It also appeared earlier (about a week)
      in the inner hair cell region than in the outer hair cell region. This dual
      gradient of maturation is in close agreement with previous data concerning the
      maturation of the cochlea.

PMID- 8306430
TI  - Ontogenic development and distribution of mRNAs of chromogranin A and B,
      secretogranin II, p65 and synaptin/synaptophysin in rat brain.
AB  - We have studied by in situ hybridization the mRNA levels of several constituents
      of transmitter storing vesicles during ontogenic development of rat brain. The
      following vesicle components were investigated: chromogranin A and B and
      secretogranin II, representing secretory peptides of large dense core vesicles,
      and the membrane proteins p65 and synaptin/synaptophysin which are found in both
      large and small synaptic vesicles but are concentrated in the latter ones.
      Several ontogenic patterns were observed: concomitant increases of most or all
      mRNAs in certain brain regions, e.g. in the thalamic nuclei at gestational day 18
      or in the cortex at postnatal day 6. For some areas selective increases for the
      various chromogranin mRNAs occurred, thus throughout development the substantia
      nigra compacta contained only the chromogranin B mRNA, whereas the lateral and
      medial geniculate nuclei and the medial tuberal nucleus expressed only
      secretogranin II mRNA. In the paraventricular hypothalamic nucleus, secretogranin
      II mRNA declined at P1 and then increased again. In the intermediate cortex there
      was a rather selective appearance of a high level of chromogranin A mRNA already
      at gestational day 16. In general the mRNAs for the membrane components become
      detectable by in situ hybridization together with the chromogranin mRNA, however,
      in the claustrum a high level of the p65 mRNA is present already at gestational
      day 16 whereas the chromogranin mRNA only appears at day 20. In some nuclei there
      was also a differential expression of the membrane components with e.g. the
      synaptophysin mRNA being present without any concomitant appearance of p65. These
      results establish that the ontogenic development of the investigated components
      in many brain areas simply indicate the starting point of biosynthesis of both
      types of vesicles finally leading to functional synapses. In those cases where a
      selective dissociation in the biosynthesis of these components occurs, a
      functional relevance of one component for a certain stage of development might be
      postulated. Since these data define the time of onset of vesicle biosynthesis in
      the various brain regions, future studies on single components of these vesicles
      can be interpreted in the context of the present findings.

PMID- 8306431
TI  - Ontogenetic SKF 38393 treatments sensitize dopamine D1 receptors in neonatal 6
      OHDA-lesioned rats.
AB  - Neonatal 6-hydroxydopamine (6-OHDA) treatment of rats is associated with
      supersensitization of the dopamine (DA) D1 agonist induction of stereotyped and
      locomotor behaviors. The present study was conducted to determine whether
      ontogenetic treatments of these rats with the DA D1 receptor agonist, SKF 38393,
      would produce a maximal DA D1 receptor supersensitivity, as measured by locomotor
      behavior in adulthood. Rat pups were treated daily with SKF 38393-HCl (3.0 mg/kg
      per day, i.p.) or saline vehicle for 28 consecutive days from birth. These
      animals were additionally treated at 3 days after birth with 6-OHDA-HBr (100
      micrograms, in each lateral ventricle, salt form) or its vehicle. Between 6 and 9
      weeks locomotor activity or stereotyped behaviors were observed after weekly
      challenge doses of SKF 38393-HCl (3.0 mg/kg, i.p.). In the neonatal 6-OHDA group,
      successive SKF 38393 treatments produced progressively greater locomotor
      activity. In the group of rats treated during postnatal ontogeny with both 6-OHDA
      and SKF 38393 daily treatments, the first adult challenge dose of SKF 38393
      produced an enhanced locomotor response, greater than that seen in other groups
      (P < 0.01). Subsequent SKF 38393 treatments of this group produced increasingly
      greater locomotor responses. SKF 38393-induced stereotyped behavioral effects
      were greater in the 6-OHDA-lesioned groups, whether or not SKF 38393 was
      administered ontogenetically. Profound reductions (> 99%) of DA and its
      metabolites were found in the striatum of neonatal 6-OHDA treated rats,
      regardless of whether SKF 38393 was co-administered ontogenetically.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8306432
TI  - Potassium-induced changes in excitability in the hippocampal CA1 region of
      immature and adult rats.
AB  - Orthodromic and spontaneous population spike activity was measured in vitro in
      the CA1 region of rat hippocampal slices to determine maturational differences in
      excitability and susceptibility to K(+)-induced seizures. Several indices of
      excitability in the CA1 region changed in a non-monotonic fashion during
      maturation, in response to step-wise increases in bath [K+]. Slices from rats 18
      22 days old, showed a greater probability of both spontaneous epileptiform
      activity and episodes of seizure-like activity followed by spreading depression,
      and more prolonged durations of evoked seizure-like events. Elevation of [K+] in
      the bathing medium increased these indices in a similar manner in older rats but
      not to the same degree as in 18- to 22-day-old rats. However, the threshold level
      of bath [K+] resulting in evoked bursts of population spikes was lower in adult
      and 28- to 32-day-old rats than in 18- to 22-day-old rats, suggesting that
      excitability is not uniformly greater at any given age. In 10- to 15-day-old
      rats, elevation of bath [K+] either produced persistent blockade of population
      responses, or increased the amplitude of the initial population spike, without
      producing bursts. Basal levels of [K+] in the interstitium of the slices
      corresponded to the various levels of [K+] placed in the bathing medium and there
      were no differences among age groups. Therefore, differences in basal [K+]o
      cannot account for the maturational changes in excitability and seizure activity.
      The period from 18-22 days of age in the rat is a useful focal point for
      investigating mechanisms underlying maturational changes in propensity to develop
      seizures.

PMID- 8306433
TI  - Developmental expression of cannabinoid receptor mRNA.
AB  - Cloning of the cannabinoid receptor affords the opportunity to examine its
      developmental expression. Other G-protein-coupled receptor systems, those for the
      opioids for example, exhibit distinct ontogenies. For the initial study,
      therefore, cannabinoid receptor mRNA expression was assessed in rat pups
      postnatal days 3, 5, 8, 10, 12, 15, 18 and 21. The brains were grossly dissected
      into cerebellum/brainstem and forebrain, and total RNA was extracted by a
      modified acid-extraction method. Expression of the cannabinoid receptor was
      analyzed by two methods: polymerase chain reaction (PCR) and Northern blot
      analysis. Oligonucleotide primers based on bp 1-21 and bp 824-843 on the opposite
      strand were chosen for use in the PCR. The probe used in the Northern blot
      analysis was a full length cDNA corresponding to the rat cannabinoid receptor and
      was cloned in our lab based on published sequence information. Our results
      indicate that by postnatal day 3, cannabinoid receptor mRNA can be detected in
      the brain. Our results further indicate that cannabinoid mRNA expression steadily
      increases in the cerebellum/brainstem until postnatal days 18-21, while
      expression in the forebrain does not change. The findings from the present study
      indicate that cannabinoid receptor mRNA is present in very young rats. Our data
      also suggest, however, regional differences in the relative expression of message
      which may parallel cerebellar proliferation and organization.

PMID- 8306434
TI  - Differential regulation of c-fos expression after cortical brain injury during
      development.
AB  - Unilateral cortical brain injury is accompanied by widespread expression of c-fos
      protein(s) throughout the wounded cortex, including areas far from the lesion
      site. Here we report that this phenomenon is differentially regulated during
      development. At postnatal day (PD) 10 or 15, when rats were sacrificed 1.5 h
      after a mechanical cortical injury, they did not show an increase in c-fos
      immunoreactivity far from the wound, despite the fact that some of these animals
      (PD 15) displayed a positive response close to the lesion. At PD 22, the same
      injury induced an increase in c-fos-immunoreactive nuclei in the piriform cortex
      ipsilateral, but not contralateral, to the lesion. This pattern was maintained up
      to at least PD 360. Similarly, the presence of c-fos-immunoreactive cells was
      observed in the ipsilateral cingulate cortex in animals 22 days old and older.
      The pattern of c-fos expression in adult animals after mechanical damage was
      compared with other models of focal brain injury: application of potassium to the
      cortical surface and devascularization. Though all models generated c-fos
      expression far from the lesion site, potassium application resulted in higher
      numbers of c-fos-positive cells, particularly in the cingulate cortex. This study
      shows that c-fos expression after cortical brain injury is regulated differently
      during development, and that dissimilar models of cortical injury induce
      qualitatively similar responses although c-fos-like protein expression differs
      quantitatively.

PMID- 8306438
TI  - The ins/del polymorphism in the signal sequence of apolipoprotein B has no effect
      on lipid parameters.
AB  - The 'ins/del' polymorphism in the signal sequence of apolipoprotein B alters the
      hydrophobicity of the signal sequence and therefore would be expected to affect
      the rate of production of apolipoprotein B (apo B) and the plasma concentrations
      of lipoproteins containing this apolipoprotein. We sought evidence for an
      association with plasma lipid levels and this polymorphism in two studies, one
      using a normal randomly selected population (N = 188) and another using a mildly
      hypercholesterolaemic group of men aged 45-64 (N = 360). The frequency of the
      rarer, 'del' allele, was the same in both groups. Likewise no differences in
      serum cholesterol, serum triglycerides, very low density lipoprotein, low density
      lipoprotein or high density lipoprotein were seen comparing homozygotes for the
      signal sequence allele within either group.

PMID- 8306436
TI  - Effects of electrical stimulation on GAP-43 expression in mouse sensory neurons.
AB  - Effects of electrical activity on GAP-43 expression were tested in mouse dorsal
      root ganglion (DRG) neurons subjected to electrical stimulation in culture.
      Patterned electrical stimulation was provided through extracellular electrodes
      placed in multicompartment cell culture chambers. Stimulation was delivered at 10
      Hz, in 0.5 s bursts every 2 s for up to 3 days. Expression of GAP-43 was assessed
      by immunocytochemistry, two ELISA methods, and Northern blot analysis within
      three experimental protocols: (1) prior to synaptogenesis, (2) after
      synaptogenesis with spinal cord neurons, and (3) within the context of activity
      dependent synaptic competition, in which synapses from active and inactive DRG
      neurons converge on the same postsynaptic neurons. None of the stimulation
      treatments produced a measurable change in GAP-43 or RNA message for the protein,
      although this electrical stimulus induces persistent changes in synaptic
      strength, and alters neurite outgrowth in these cultures. The decline in GAP-43
      levels between 1 and 3 weeks in culture, which has been reported in other
      studies, was readily detectable by our measurements. We conclude that regulation
      of GAP-43 expression is not required for activity-dependent regulation of growth
      cone motility, synaptogenesis and synapse elimination, or changes in synaptic
      strength. Instead, post-translational modification, such as phosphorylation, may
      be the primary means of regulating any GAP-43 functions associated with these
      activity-dependent processes.

PMID- 8306437
TI  - Rapid enzyme immunoassay of anti-streptokinase antibodies in human plasma.
AB  - A simple enzyme immunoassay for determination of anti-streptokinase antibodies
      (aSKa) in plasma is described. Commercially available reagents have been used for
      the assay, which is calibrated with a reference preparation of aSKa containing
      100 AU/ml. The assay is specific and reproducible with a variation coefficient of
      4.8%. In healthy individuals a broad range of values between 4 and 291 AU/ml was
      observed with a large difference between the mean and median value (55 AU/ml and
      27 AU/ml, respectively). Data from a study on 21 patients with myocardial
      infarction treated with the streptokinase derivative antistreplase suggest that a
      high titre of aSKa before treatment is associated with failure of thrombolytic
      therapy. The assay procedure can be shortened to 0.5 h to screen patients for a
      high aSKa level. This assay allows a more routine assessment of aSKa in the
      clinic.

PMID- 8306435
TI  - Age-dependence of a 6-hydroxydopamine lesion on SKF 38393- and m
      chlorophenylpiperazine-induced oral activity responses of rats.
AB  - Neonatal 6-hydroxydopamine (6-OHDA) treatment is associated with destruction of
      dopamine (DA) fibers and subsequent sprouting of serotonin (5-HT) fibers in the
      striatum of rats. Enhanced oral activity responses to SKF 38393 and m
      chlorophenylpiperazine (m-CPP), respective agonists for the DA D1 receptor
      complex and 5-HT2C receptor complex, ensue. To study the ontogenetic nature of
      this effect, rats were treated at birth, 3 days, 7 days, 10 days or 14 days with
      6-OHDA-HBr (200 micrograms i.c.v.; salt form), following desipramine-HCl
      pretreatment (20 mg/kg i.p., 1 h; base form). Another group of rats was treated
      at 35 days and again at 42 days with 6-OHDA-HBr (300 micrograms i.c.v.),
      following desipramine-HCl (20 mg/kg i.p., 1 h) and pargyline-HCl (50 mg/kg i.p.,
      30 min). In rats treated from birth to 10 days, 6-OHDA reduced striatal DA
      content at 5 months by > or = 94%. Striatal 5-HT content was elevated by 28% to
      51%, but only in rats treated with 6-OHDA at 7 days from birth or earlier. An
      enhanced oral activity response to SKF 38393-HCl (0.03 to 1.0 mg/kg i.p.) was
      absent in rats treated 7 days or later, and the change in SKF 38393 effect was
      correlated with a change in striatal DA content. An enhanced response to m
      CPP.2HCl (0.3 to 6.0 mg/kg i.p.) was absent after treatment at 14 or 35 days,
      when striatal DA content was reduced only 44% to 63% and 5-HT content was not
      changed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306439
TI  - Fluorescence-based diagnosis of lipid storage diseases by analysis of the culture
      medium of skin fibroblasts.
AB  - Glycosphingolipids, labeled with the fluorescent probe lissamine rhodamine were
      administered to skin fibroblasts in culture and were hydrolyzed in the intact
      cells to the corresponding lissamine rhodamine ceramide (N-acylsphingosine). This
      fluorescent ceramide was converted in the intact cells to the corresponding
      sphingomyelin which was secreted into the culture medium. In comparison, ceramide
      is not formed in cells derived from patients with lipid storage diseases, because
      of deficiencies in lysosomal glycolipid hydrolases. Consequently, fluorescent
      sphingomyelin was absent from the culture medium or present in considerably
      reduced quantities. This provided a procedure for diagnosing lipidoses, by
      analyzing the lissamine rhodamine sphingomyelin content in the culture medium,
      while maintaining the cells intact.

PMID- 8306441
TI  - Rapid determination of glutamine in biological samples by high-performance liquid
      chromatography.
AB  - A high-performance liquid chromatographic method for the determination of
      glutamine in biological samples is presented. Glutamine was derivatized with
      ortho-phthalaldehyde reagent containing 3-mercaptopropionic acid and separated by
      reversed phase chromatography on a C18 column containing 3-microns particles. No
      interference from other amino acids was observed. The assay was linear over a
      range from 1 to 2,000 mumol/l. Analytical recovery of plasma samples spiked with
      glutamine was 98.6 +/- 3.8%. Within- and between-batch imprecision were 1.5% and
      2.2%, respectively. The derivatization step was fully automated. Total analysis
      time, including derivatization and chromatography, amounted to 6 min. The method
      can be used for the determination of glutamine in plasma, urine, cerebrospinal
      fluid and tissue homogenates.

PMID- 8306443
TI  - High-performance liquid chromatographic microassay for L-glutamate:glyoxylate
      aminotransferase activity in human liver. Application in primary hyperoxaluria
      type 1.
AB  - A rapid and sensitive liquid chromatographic technique to determine L
      glutamate:glyoxylate and aminotransferase (EC 2.6.1.4) activity in human liver is
      described. Homogenised tissue was incubated for 60 min in the presence of
      substrates and the 2-oxoglutarate generated was converted into the corresponding
      phenylhydrazone which was determined using reversed-phase high-performance liquid
      chromatography. The procedure allowed the detection of the enzyme activity
      expressed by 7.5 micrograms of liver protein, it was more sensitive and less time
      consuming than the spectrophotometric procedure previously used. No significant
      differences were found between normal controls and patients with primary
      hyperoxaluria. In an 8-month-infant with primary hyperoxaluria type 1, the enzyme
      activity was reduced to 16% of the average control values.

PMID- 8306442
TI  - Increased excretion of endogenous urinary leukotriene E4 in extrahepatic
      cholestasis.
AB  - The cysteinyl leukotrienes LTC4, LTD4 and LTE4 are potent lipid mediators
      eliminated from the blood circulation mainly due to uptake by the liver and the
      kidneys. In man hepatobiliary elimination of cysteinyl leukotrienes predominates
      over renal excretion. In the present study, the urine from patients with
      extrahepatic cholestasis (n = 25) and age- and sex-matched healthy control
      subjects (n = 25) was analyzed for endogenous LTE4, the predominant metabolite of
      LTC4 excreted into urine. LTE4 was separated by reversed-phase high-performance
      liquid chromatography and subsequently quantified by enzyme immunoassay. Healthy
      subjects excreted a median concentration of 14 nmol LTE4/mol creatinine (range 5
      24 nmol/mol creatinine). Its median concentration increased significantly to more
      than 5-fold higher levels to 74 nmol LTE4/mol creatinine (range 52-93 nmol/mol
      creatinine) in patients with extrahepatic cholestasis (P < 0.01). These results
      indicate that extrahepatic cholestasis leads to a compensatory diversion of
      cysteinyl leukotriene elimination to the kidney with subsequent increased
      excretion of LTE4 into urine.

PMID- 8306444
TI  - Simultaneous determination of lead, bismuth and thallium in plasma and urine by
      inductively coupled plasma mass spectrometry.

PMID- 8306440
TI  - Two-dimensional gel electrophoresis of four serum samples from patients with IgD
      myeloma.
AB  - Sera containing IgD paraprotein present problems in identifying patients with
      monoclonal gammopathies because only a small or even no spike may be present on
      standard serum protein electrophoresis. We have detected heavy chains of IgD
      monoclonal protein by means of high resolution two-dimensional gel
      electrophoresis. Besides clearly identifying delta heavy chains in maps of serum
      proteins, we also found size and charge heterogeneity of monoclonal
      immunoglobulins. The results demonstrate the usefulness of two-dimensional gel
      electrophoresis in the analysis of selected cases of immunoglobulin malignancies.

PMID- 8306447
TI  - Effects of gemfibrozil on the activities of plasma lipolytic enzymes in
      normolipidemic subjects.

PMID- 8306446
TI  - Compact gas chromatography used with thin-layer chromatography for assessment of
      abnormalities of organic acids.

PMID- 8306445
TI  - Rapid automated enzymatic measurement of phenylalanine in plasma and blood spots.

PMID- 8306448
TI  - Variation in the amount of stimulatory GTP-binding protein (Gs) in human
      erythrocyte membranes in relation to alcohol consumption.

PMID- 8306450
TI  - Neonatal screening for maple syrup urine disease by an enzyme-mediated
      colorimetric method.
AB  - A microplate-based, enzyme-mediated, colorimetric method using L-leucine
      dehydrogenase (EC 1.4.1.9) has been developed for the determination of the
      combined branched-chain amino acids in plasma and blood-spot specimens. The test
      exhibits acceptable precision and fits into a new concept according to which the
      different parameters of neonatal screening programs for metabolic disorders, such
      as phenylalanine (phenylketonuria), galactose/galactose-1-phosphate
      (galactosemia) and branched-chain amino acids (maple syrup urine disease) can be
      measured in the same blood-spot eluate by use of different specific NAD(H)
      dependent enzymes.

PMID- 8306449
TI  - A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 1
      (interstitial collagenase) using monoclonal antibodies.
AB  - Interstitial collagenase (EC 3.4.24.7, matrix metalloproteinase-1, MMP-1) is
      synthesized and secreted by many cells, and plays an important role in a wide
      variety of pathophysiological degradation processes of extracellular matrices.
      The activity of MMP-1 is regulated by tissue inhibitors of metalloproteinases,
      TIMP-1 or TIMP-2, which form a non-covalent complex with the active enzyme. We
      raised monoclonal antibodies against zymogen of MMP-1, proMMP-1 purified from
      human skin fibroblasts. The antibodies recognized both precursor and active forms
      of MMP-1, but did not cross-react with 72-kDa and 92-kDa gelatinase/type IV
      collagenases or stromelysin-1. A specific and sensitive one-step sandwich enzyme
      immunoassay for human MMP-1 was developed using a solid phase monoclonal antibody
      and a horseradish peroxidase-labeled monoclonal antibody (Fab'). The assay can be
      completed within 1 h (30 min for immunoreaction and 15 min for color development)
      and the sensitivity is 0.12 microgram/l with the linearity between 0.12 and 10
      micrograms/l. Active MMP-1 shows 1.3-fold higher absorption at 492 nm than proMMP
      1. However, the recognition rate of MMP-1 is decreased to approximately 50% and <
      3% for the MMP-1-TIMP-1 and MMP-1-TIMP-2 complex forms, respectively. The MMP-1
      levels in human sera from 120 healthy subjects are shown to be in the range of
      8.5 +/- 5.2 micrograms/l (mean +/- S.D.) and the levels of 95% of the samples
      range from 0 to 20 micrograms/l.

PMID- 8306451
TI  - Dissipation of the calcium gradient in human erythrocytes results in increased
      heat production.
AB  - Heat production rates were measured by a microcalorimetric method in suspended
      human erythrocytes in the absence and presence of different concentrations of the
      divalent cationophore A23187. Determinations were carried out during 60 min under
      static conditions on erythrocytes incubated in various isotonic media at 37
      degrees C, pH 7.35. In incubations containing the ionophore, time-power curves
      showed an early peak followed by a descending slope levelling off at a steady
      state after 30-60 min. In contrast, the controls lacked the early peak, showing
      hyperbolic ascending curve profiles before reaching steady state. The appearance
      of the early peak in the presence of ionophore was dependent upon the composition
      of the medium, both Mg2+ ions and glucose being decisive. Likewise, dose-response
      relationships concerning heat production at 60 min depended on the composition of
      the media. In a basic incubation medium lacking Mg2+ and glucose, no effect was
      seen on heat production by the ionophore (1-3 mumol/l). Rather modest effects
      were obtained by the ionophore at 2 and 3 mumol/l when Mg2+ was present. A clear
      cut dose-response relationship was observed in a Mg2+ and glucose enriched medium
      for the ionophore from 1-3 mumol/l. The significant increase in heat production
      observed at 60 min with 2 mumol/l of A23187 in the Mg2+ and glucose enriched
      medium was abolished by 1 mmol/l EGTA. Calmidazolium, a calmodulin antagonist,
      could only marginally reduce the ionophoric effect on heat production. It was
      concluded that the appearance of the early peak was not the result of an increase
      in glycolytic rate but rather a consequence of the ionophoric action on the Ca2+
      gradient.

PMID- 8306453
TI  - Radioimmunoassay of glutathione peroxidase in human serum.
AB  - Glutathione peroxidase (GSHPx) was purified from human serum and used for
      immunization of rabbits. Antiserum bound up to 75% of added 125I-GSHPx after
      precipitation with a second antibody. Human serum, but not sera from eight animal
      species, inhibited the binding of labelled GSHPx, indicating that the antiserum
      did not react with GSHPx from these species. GSHPx could be measured in less than
      10 microliters of human serum by radioimmunoassay. In sera with widely varying
      selenium concentrations (0.1-2.9 mumol/l) the amount of GSHPx protein (0.3-6.3
      mg/l) was strongly correlated with GSHPx activity (r = 0.94) and it was also
      correlated with serum selenium concentrations (r = 0.64). This indicates that
      GSHPx protein may be a valuable biological marker of selenium status. In samples
      with serum selenium concentrations of 0.8-1.2 mumol/l, the concentration of GSHPx
      was 3.3 (0.4) mg/l (mean (S.D.)), or 0.04 (0.005) mumol/l. This corresponded to
      0.16 (0.02) mumol/l of GSHPx selenium and 16% (2.8)% of total serum selenium. The
      data suggest that the method can be used to measure the proportion of serum
      selenium that is located in GSHPx. Following storage of serum at room
      temperature, both serum GSHPx protein and activity declined, but addition of
      glutathione protected both GSHPx protein and activity.

PMID- 8306452
TI  - Determination of changes in serum lathosterol during treatment with simvastatin
      to evaluate the role of lathosterol as a parameter for whole body cholesterol
      synthesis.
AB  - Serum levels of cholesterol and the cholesterol precursor lathosterol were
      determined in five healthy volunteers who took 20 mg simvastatin daily during 1
      week. During this period and for the following 5 days blood samples were
      collected. Five days after ingestion of simvastatin, serum lathosterol had
      already reached a steady-state level and its concentration decreased by 55-73%.
      In contrast, the cholesterol concentration decreased only by 17-29% and did not
      reach a steady-state level even after 7 days of treatment. After withdrawal of
      simvastatin, serum lathosterol quickly rose to pretreatment values. From the data
      a mean half-life of lathosterol could be calculated of 23.5 +/- 6.6 h during
      treatment with simvastatin and of 28.7 +/- 15.1 h after its withdrawal, taking,
      respectively, the decrease and increase of serum lathosterol into account. From
      these data it can be concluded that serum lathosterol is also a good parameter
      for determining whole body cholesterol synthesis during non-steady-state
      conditions, although plasma mevalonic acid, another (early) cholesterol
      precursor, is preferred owning to its much shorter reported half-life.

PMID- 8306454
TI  - Lipoprotein(a) phenotyping using a computerized micro scale and phenotype
      frequencies in a healthy Japanese population.

PMID- 8306455
TI  - Changes in glutathione metabolic enzymes in erythrocytes of Plasmodium vivax
      infected patients.

PMID- 8306456
TI  - The vitamin A fat-loading test in young normolipidemic subjects.

PMID- 8306457
TI  - Abnormally fucosylated haptoglobin as a marker for alcoholic liver disease but
      not excessive alcohol consumption or non-alcoholic liver disease.

PMID- 8306458
TI  - Differences in the time course of creatine kinase-MB activity and mass
      concentration after acute myocardial infarction.

PMID- 8306459
TI  - Simple mixing technique for the preparation of blood samples of known oxygen
      saturation.
AB  - A mixing technique for the preparation of whole blood samples of known oxygen
      saturation is described. The technique, which uses basic equipment and a very
      simple procedure, is capable of accuracies better than +/- 2% across the full
      range of saturation and is extendable to use with other applications with only
      slight reductions in accuracy.

PMID- 8306460
TI  - Effect of ethanol on prolidase I and prolinase activity in the human hepatoma
      cell line Hep G2.

PMID- 8306461
TI  - Evaluation of thyroid function in patients with thyroid hormone autoantibodies.
AB  - Serum free thyroxine (FT4) levels were measured in patients with Hashimoto's
      thyroiditis and Graves' disease who were seropositive for thyroid hormone
      autoantibodies. The methods used were equilibrium dialysis/radioimmunoassay (FT4
      by equilibrium dialysis, Nichols Institute) and FT4 analog radioimmunoassay
      (Amerlex MFT4) before and after treatment of sera with 12.5% polyethylene glycol
      (PEG). Furthermore, FT4 measurement in the PEG-treated sera was done using two
      other analog radioimmunoassays (DPC FT4 Kit and N-FT4 Corning). Serum thyrotropin
      (TSH) concentration before and after i.v. infusion of thyrotropin releasing
      hormone (TRH) was measured in five cases of Hashimoto's thyroiditis and four
      cases of Graves' disease with thyroid hormone autoantibodies. Although FT4
      determination by analog tracer radioimmunoassays showed unusually high values for
      the hormone, results obtained by an equilibrium dialysis/radioimmunoassay method
      showed compatible values with basal TSH. Furthermore, FT4 concentrations measured
      with Amerlex MFT4 after treatment of sera with 12.5% PEG, correlated well with
      the values obtained by equilibrium dialysis/radioimmunoassay (r = 0.98, P <
      0.001). Similar results were obtained with two other analog FT4 radioimmunoassays
      after treatment of sera with PEG. These results indicate that real FT4 values in
      patients with thyroid hormone autoantibodies are compatible with basal TSH
      concentrations. The presence of thyroid hormone autoantibodies per se does not
      affect the control mechanism of the hypothalamo-pituitary-thyroid axis. It was
      concluded that measurement of basal TSH as well as FT4 values by either
      equilibrium dialysis/radioimmunoassay or analog radioimmunoassays after PEG
      treatment provides clinicians with valid information for assessment of the
      precise status of thyroid function in patients with thyroid hormone
      autoantibodies.

PMID- 8306462
TI  - Blood and liver lipid peroxide status after chronic ethanol administration in
      rats.
AB  - During the last decades a vast number of reports have aimed at elucidating the
      mechanisms behind alcohol-related organ injury, but the manner in which ethanol
      induces, e.g., liver damage is still an enigma. Increased oxidative stress has
      been put forward as one possible mechanism behind alcohol-related tissue damage.
      This paper focuses on the effect of chronic ethanol consumption on antioxidant
      status and lipid peroxide levels in blood and liver of rats. Alcohol was given
      twice daily in a total dose of 5 g ethanol/kg body wt. per day divided into two
      2.5 g ethanol/kg body wt. doses as a 50% water solution, by gavage over 4 weeks.
      Chronic ethanol ingestion led neither to a significant change in lipid peroxide
      formation nor to a significant change in enzymatic antioxidant activities. Only
      concentrations of oxidized glutathione and of other non-enzymatic antioxidant
      such as vitamin E showed a tendency to decrease after alcohol application. The
      data presented could serve to emphasize no involvement of free radical-induced
      lipoperoxidation in the pathogenesis of ethanolic liver diseases.

PMID- 8306463
TI  - Evidence for a multifactorial control of serum erythropoietin concentration in
      liver disease.
AB  - We measured serum erythropoietin (EPO) immunoenzymatically in 245 subjects (151
      male, 94 female) to investigate the pathophysiology of its liberation in patients
      with liver disease. Twelve patients had acute hepatitis, 60 mild chronic liver
      disease (CLD), 50 cirrhosis (CIR), 43 hepatocellular carcinoma (HCC), 16
      malignant extrahepatic disease, 32 benign extrahepatic disease (BEN); 32 subjects
      served as healthy controls. Higher EPO levels were found in all groups of
      patients as compared with controls (Bonferroni's test, P < 0.01); CIR and HCC had
      higher values than CLD and BEN (P < 0.01). By multiple regression analysis, EPO
      correlated with haematocrit, cholinesterase and C-reactive protein (F = 18.63, P
      < 0.0001). Thus, circulating EPO increases in patients with liver disease,
      particularly in its more advanced forms. Besides anaemia, both impairment of
      liver function (possibly via decreased EPO metabolism) and inflammation seem to
      play contributory roles in elevating serum EPO.

PMID- 8306464
TI  - Levels and physicochemical properties of lipoprotein subclasses in moderate
      hypertriglyceridemia.
AB  - Moderate hypertriglyceridemia is associated with several abnormalities of the
      plasma lipoprotein particles and it may be a risk factor for atherosclerotic
      vascular diseases. Plasma lipid, lipoprotein and apolipoprotein levels, as well
      as lipoprotein composition and physical properties, were examined by
      ultracentrifugation in a zonal rotor and by gradient gel electrophoresis in 14
      patients with moderate hypertriglyceridemia (plasma triglycerides 4.00 +/- 0.32
      mmol/l, mean +/- S.D.) and in 14 control subjects. Based on zonal
      ultracentrifugation hypertriglyceridemic patients have higher levels of
      cholesterol in all VLDL subclasses (Sf > 200, 100-200, 60-100 and 20-60), in IDL
      and in small and dense LDL. Both HDL2 and HDL3 cholesterol levels are reduced.
      The LDL flotation rate is inversely related to plasma triglyceride levels, thus
      indicating that the higher the plasma triglycerides the smaller and/or denser the
      LDL are. The triglyceride percent content of LDL2 and HDL3 is increased, while
      that of esterified cholesterol is reduced in hypertriglyceridemic patients.
      Gradient gel electrophoresis shows that the LDL peak size is lower (25.2 +/- 0.5
      nm, mean +/- S.D.) in hypertriglyceridemic than in control subjects (27.1 +/- 0.4
      nm; P < 0.0001). Considering both hypertriglyceridemic and control subjects the
      LDL peak effluent volume from the zonal rotor (which reflects the LDL flotation
      rate) is inversely related to the LDL peak size determined by gradient gel
      electrophoresis (r = -0.71; P = 0.0006) and the plasma triglyceride levels are
      related to LDL peak effluent volume (r = 0.74; P = 0.0002) and to LDL peak size
      (r = -0.95; P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306465
TI  - Postoperative studies on parathyroid hormone secretion in patients operated on
      for primary hyperparathyroidism.
AB  - The secretion of intact parathyroid hormone (PTH) was investigated in 11 patients
      operated on for parathyroid adenoma at 1 year after surgery and compared with
      that of seven healthy individuals and five patients operated on because of
      clinical and biochemical signs of primary hyperparathyroidism with equivocal
      diagnosis after surgery. The investigation was performed by infusing Na2EDTA and
      CaCl2 at constant rates. No significant difference was found in the
      suppressibility of PTH secretion by calcium. The set point (the calcium
      concentration required for half-maximal inhibition of PTH secretion) was slightly
      lower in patients (1.20 +/- 0.02 mmol/l) compared with healthy subjects (1.23 +/-
      0.03 mmol/l; P < 0.05). During the hypocalcemic EDTA infusion, the secretion of
      PTH was higher in controls compared with patients (P < 0.01). By comparing the
      data from the infusion tests in patients operated on for parathyroid adenomas
      with the data obtained from the patients with equivocal diagnosis after
      parathyroid surgery, a good probability for the diagnosis could be obtained.

PMID- 8306466
TI  - Bismuth in human serum: reference interval and concentrations after intake of a
      therapeutic dose of colloidal bismuth subcitrate.
AB  - A sensitive method for the determination of the bismuth concentration in human
      serum is described. Analyses were carried out by inductively coupled plasma-mass
      spectrometry (ICP-MS), after a simple dilution of the samples with nitric acid.
      The detection limit of the applied method is 0.007 microgram/l whereas relative
      standard deviations varied from 5.7 to 13.6%. Determination of reference values
      in human serum of healthy adults gave a range from < 0.007 to 0.067 microgram/l
      (19 persons). Bismuth concentrations in serum were also measured before, during
      and after the intake of therapeutic doses of colloidal bismuth subcitrate (CBS).
      About 1.5-2 h after the intake of one tablet of CBS, the bismuth concentration in
      serum was found to have increased 51-1483 times (two apparently healthy
      volunteers and six hospitalized patients), showing that the serum bismuth
      concentrations can increase by several orders of magnitude during the intake of
      CBS. During the intake of four tablets of CBS per day by two apparently healthy
      volunteers, bismuth concentrations in serum after an overnight fast were found to
      be, respectively, 5.56 and 8.1 micrograms/l on day 15 and 4.28 and 13.6
      micrograms/l on day 29. After stopping the therapy, the concentration of bismuth
      in serum slowly returned towards normal over a period of months.

PMID- 8306467
TI  - Studies on the extraction of phospholipids from erythrocyte membranes in the rat.
AB  - The effects of choice of solvent and period of extraction on recovery of
      phospholipid classes extracted from rat erythrocyte membranes were investigated.
      For extraction of phosphatidylserine (PS) the best recovery was achieved using
      chloroform-methanol (2:1, v/v), for diacyl phosphatidylethanolamine (PE) acetone
      isopropanol (3:2, v/v), and for extraction of plasmalogen PE, phosphatidylcholine
      (PC) and sphingomyelin (SM) using hexane-isopropanol (3:2, v/v). Using hexane
      isopropanol (3:2, v/v), boiling during the extraction increased the recovery of
      some of the individual phospholipid classes whereas mechanical treatment of the
      sample had only a slight effect. Furthermore, the fatty acid composition of PS
      and PE varied most with different extraction conditions and the phospholipid
      classes PC and SM were extracted more readily from rat erythrocyte membranes than
      PS, diacyl and plasmalogen PE.

PMID- 8306468
TI  - Energy expenditure and body composition in growth hormone deficient adults on
      exogenous growth hormone.
AB  - OBJECTIVES: We assessed whether the obesity observed in growth hormone deficient
      adults is maintained by a reduction in energy expenditure. We studied the effects
      of exogenous growth hormone on energy expenditure and body composition. DESIGN:
      We performed an open study with growth hormone administered at 0.5 units per
      kilogram ideal body weight per week for 3 months. PATIENTS: Seven growth hormone
      deficient adults were studied. Thirty-eight healthy volunteers had their resting
      metabolic rate measured, with seven of them proceeding to have their total energy
      expenditure assessed. MEASUREMENTS: Total energy expenditure was measured by the
      doubly labelled water method (D2O18), resting metabolic rate by ventilated hood
      indirect calorimetry, and fat free mass from the dilution volume of oxygen-18.
      Body composition and components of energy expenditure were assessed before, at 2
      weeks and at the end of the 3-month treatment period on exogenous growth hormone.
      RESULTS: Growth hormone deficient adults did not have a low total energy
      expenditure compared to healthy controls (13.12 vs 12.75 MJ/24 h) with only one
      patient expending less than 10 MJ/24 h. None had a resting metabolic rate lower
      than the 95% confidence limits of normality. The amount of energy expended on
      physical activity and thermogenesis was significant (6.54 MJ/24 h) and was
      similar to healthy controls (6.47 MJ/24 h). Resting metabolic rate increased by
      15.9% after 14 days on exogenous growth hormone and was elevated 12.1% after 3
      months treatment but the ratio to fat-free mass remained unaltered. Total energy
      expenditure increased by 13.4% after 14 days therapy. Fat-free mass increased
      significantly after 3 months treatment by (mean) 4.5 kg with no change in fat
      mass and no loss in body weight. CONCLUSIONS: Obesity maintenance in growth
      hormone deficient adults is not a consequence of reduced total energy expenditure
      or a reduced exercise energy output. There was also no evidence for an energy
      sparing mechanism. Energy expenditure was increased by exogenous growth hormone
      but was not associated with a loss in fat mass or body weight suggesting the need
      for dietetic advice for those already obese at the outset of therapy.

PMID- 8306469
TI  - Decreased psychological well-being in adult patients with growth hormone
      deficiency.
AB  - OBJECTIVE: Besides effects on body composition, bone mineral content and lipid
      metabolism, GH seems to influence quality of life, according to previous studies
      of limited numbers of patients with GH deficiency of childhood and adult origin.
      In this study psychological well-being was assessed in a large number of patients
      with GH deficiency of adult origin. DESIGN: A follow-up study of patients with
      hypopituitarism on routine replacement therapy with L-thyroxine, cortisone
      acetate and sex steroids. PATIENTS: Eighty-six patients (51 men, mean age 55.4
      years and 35 women, mean age 54.9 years) diagnosed as having growth hormone
      deficiency on the basis of low IGF-I concentration or a maximum GH response less
      than 5 mU/l after an insulin/glucagon tolerance test. MEASUREMENTS: Quality of
      life was measured with a self-rating questionnaire, the Nottingham Health
      Profile, and the results were compared with the results from 86 controls matched
      for age, gender, marital status and socioeconomic class. Furthermore, the
      observed and expected number of disablement pensions were calculated. RESULTS:
      The mean total score of the patients was higher, i.e. worse (P < 0.05), than that
      of the matching controls, indicating a higher level of perceived health problems
      among the patients. There were higher scores (poorer life quality) for energy (P
      < 0.001), social isolation (P < 0.01), emotional reaction (P = 0.056) and sex
      life (P < 0.001) among patients compared with controls. Finally, the observed
      number of disablement pension among the patients tended to be higher than
      expected (19 vs 12.4, P = 0.09). CONCLUSIONS: Adult patients with GH deficiency
      have a decreased psychological well-being in terms of energy, social isolation
      and emotional reaction and a disturbed sex life compared with normals.
      Furthermore, there is a tendency to a higher frequency of early retirement.

PMID- 8306470
TI  - Oncoprotein immunoreactivity in human pituitary tumours.
AB  - OBJECTIVE AND DESIGN: The immediate early gene locus AP-1, incorporating the
      cellular oncogenes c-fos and c-jun (and their oncoprotein products Fos and Jun
      respectively) play a key role in regulating cell growth and differentiation. The
      myc-gene is also known to promote cell growth. In order to investigate the
      possible role of these oncogenes in human pituitary adenomas, Fos, Jun and Myc
      oncoprotein immunoreactivities were assessed in surgically resected pituitary
      adenomas in relation to in-vivo characteristics (hormone secretion, size and
      invasiveness) and an in-vitro index of cell proliferation (Ki-67
      immunoreactivity). Thirty-three human pituitary adenomas and 16 normal pituitary
      glands were examined. MEASUREMENTS: Oncoprotein immunoreactivity was recorded as
      present (+) or absent (-), and Ki-67 labelling indices were scored
      quantitatively. Tumour size was scored from CT scan appearances and radiographic
      evidence of bone erosion was noted. RESULTS: Oncoprotein immunoreactivity was
      present in a total of 32/33 cases. Myc immunoreactivity was restricted to the
      only ACTH-secreting tumour in the series (1/33). Ki-67 immunoreactivity was
      present in 24/32 cases and labelling indices varied from 0.1 to 3.2%.
      CONCLUSIONS: Oncoprotein immunoreactivity did not correlate with hormonal
      profile, bone erosion or the size of the proliferating compartment estimated by
      Ki-67 labelling indices. Although oncoprotein expression is common in human
      pituitary adenomas, its significance remains to be elucidated.

PMID- 8306471
TI  - Influence of sodium valproate on medium-late luteal phase pulsatile LH secretion
      in normal women.
AB  - OBJECTIVE: It is not known whether gamma-aminobutyric acid (GABA) is involved in
      control of pulsatile LH secretion in human beings. Previous work by our group has
      shown that manipulation of the GABAergic system with sodium valproate does not
      affect pulsatile LH secretion in normal women in the late follicular phase.
      However, it has been suggested that steroid levels are critical for the influence
      of GABA upon hormone secretion; in particular, progesterone has been said to
      enhance inhibition by GABA. In this work we studied the effect of sodium
      valproate on pulsatile LH secretion in medium-late luteal phase of normal women.
      DESIGN: Six normal young women were studied over an 8-hour period in two
      successive menstrual cycles. On each occasion blood samples were taken every 10
      minutes between 1000 and 1800 h. We administered 400 mg of sodium valproate every
      8 hours on the 7 days preceding their second cycle and additional 400 mg at 0900
      and 1400 h on the day of the study. Ovulation day was estimated by means of
      serial ovarian ultrasound examinations and confirmed by serum progesterone
      concentrations. MEASUREMENTS: In each cycle, LH, oestradiol and progesterone were
      determined by radioimmunoassay and sodium valproate by repolarization
      fluorescence spectrophotometry. The series of LH levels was smoothed for 1-minute
      sampling periods by means of a spline function and analysed by means of a program
      developed in our laboratory and written in Fortran 77. The program deconvolved
      the signal and calculated the pulse area, pulse duration, interpulse interval and
      number of pulses. LH pulse identification on the deconvolved signals was
      performed using our own method based on Friedman's non-parametric statistic. The
      statistical significance of differences between parameters was estimated using
      the Mann-Whitney test and Wilcoxon signed rank test. RESULTS: There were no
      significant differences in LH pulse area, pulse duration, interpulse interval or
      number of pulses with the administration of sodium valproate. CONCLUSIONS:
      Activation of the GABAergic system with sodium valproate had no biologically
      significant effect on the mid-late luteal phase pulsatile LH secretion in normal
      women.

PMID- 8306472
TI  - Serum FSH and testicular morphology in male infertility.
AB  - OBJECTIVE: In patients with azoospermia serum FSH helps to differentiate between
      obstruction or spermatogenetic dysfunction as the possible cause of this
      condition. The role of FSH in the diagnosis of infertile men with
      oligoasthenoteratozoospermia is less clearly defined. In order to evaluate the
      diagnostic significance of serum FSH in the management of male infertility, serum
      FSH levels were related to testicular morphology from bilateral biopsies of
      infertile men. DESIGN AND PATIENTS: Testicular biopsies were obtained from 213
      infertile men and evaluated in semi-thin sections. Biopsies were performed either
      in order to distinguish between obstructive and non-obstructive azoospermia or
      because of subnormal semen variables when history, clinical investigation and
      hormone levels failed to explain infertility. Serum FSH was measured by
      fluoroimmunoassay. RESULTS: Patients were divided into five groups on the basis
      of morphological criteria. The mean serum FSH value of patients with obstructive
      azoospermia and normal histology (group 1, n = 14) was normal (3.0 (2.2-4.1)
      IU/l) (mean (95% confidence limits)). Serum levels of FSH in non-obstructive
      oligo or azoospermia were as follows: group 2: mixed atrophy of tubular tissue
      without focal Sertoli cell only syndrome (SCO) (n = 104) (4.5 (4.0-5.1) IU/l),
      group 3: mixed atrophy with unilateral focal Sertoli cell only (n = 39) (7.4 (6.1
      9.0) IU/l), group 4: mixed atrophy with bilateral focal SCO (n = 36) (10.7 (8.7
      13.0) IU/l). Group 5: bilateral or unilateral total Sertoli cell only (n = 20)
      (16.0 (12.1-20.9) IU/l). Mean serum FSH levels were significantly different
      between all groups (P < 0.05). CONCLUSIONS: Elevation of serum FSH correlates
      with the appearance of Sertoli cell only tubules. Elevated FSH serum levels make
      testicular biopsies superfluous for diagnostic purposes, but normal FSH does not
      exclude severe derangement of spermatogenesis in individual cases.

PMID- 8306473
TI  - Pituitary stone: two cases of densely calcified thyrotrophin-secreting pituitary
      adenomas.
AB  - Calcification is a well recognized but relatively uncommon feature of prolactin
      secreting, growth hormone-secreting and non-functional pituitary tumours. It
      varies in extent, but rarely exceeds a tiny amount histologically or
      radiologically. Thyrotroph adenomas are the rarest of the secretory pituitary
      tumours, accounting for less than 1% of cases, and partial calcification of such
      lesions has been reported in only three cases. We describe two patients in whom
      the clinical and biochemical features indicated the presence of a TSH-secreting
      adenoma and radiology demonstrated a large 'pituitary stone'. One patient, a 59
      year-old female, initially presented with hyperthyroidism, aged 18, and was
      rendered euthyroid by two subtotal thyroidectomies before a pituitary lesion was
      suspected, over 20 years later. Autonomous secretion of thyrotrophin was
      demonstrated by dynamic tests, and the failure of exogenous T3 to reduce the
      serum TSH. In the absence of tumour expansion and compressive symptoms, pituitary
      surgery was not undertaken. At the age of 56, she developed symptoms of
      intermittent ataxia and diplopia, culminating in a focal seizure, and was found
      on CT scan to have, in addition to the pituitary lesion, a parasagittal
      meningioma. This was successfully removed at craniotomy. In the second patient, a
      42-year-old male, the finding of hyperthyroidism in association with an elevated
      TSH concentration led to the discovery of a pituitary stone which was removed
      transethmoidally, together with surrounding adenomatous tissue which stained
      positively for TSH on immunocytochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306474
TI  - Acute suppurative thyroiditis in an asymptomatic woman: an atypical presentation
      simulating thyroid carcinoma.
AB  - Patients with acute suppurative thyroiditis usually have pain or tenderness in
      the anterior part of the neck associated with erythema and dysphagia. A 26-year
      old Japanese woman with none of these symptoms presented with a left anterior
      cervical mass. Since physical examination and laboratory studies showed a firm
      and irregular tumour located in the left lobe of the thyroid without any
      inflammatory signs, we made a diagnosis of thyroid carcinoma. After surgery,
      histological examination of the thyroid specimen revealed various changes of
      severe inflammation, and a barium swallow demonstrated a left pyriform sinus
      fistula. We describe here a unique case of acute suppurative thyroiditis in an
      asymptomatic woman.

PMID- 8306475
TI  - Cortisol and oocyte quality.

PMID- 8306477
TI  - Localization of pancreatic endocrine tumours.

PMID- 8306476
TI  - Effects of oestrogen on progesterone synthesis and arachidonic acid metabolism in
      human luteal cells.
AB  - OBJECTIVE: Locally produced oestrogens and prostaglandins (PGs) are implicated in
      the regulation of luteal lifespan in the human ovary. This study (1) assesses
      direct effects of these factors on progesterone synthesis in isolated luteal
      cells, and (2) explores interactions between luteal age and treatment with
      gonadotrophin or oestrogen on the metabolism of arachidonic acid (prostaglandin
      precursor) by steroidogenic luteal cells in vitro. DESIGN: Primary monolayer
      cultures of human luteal cells obtained at different stages of the luteal phase
      were used to investigate the effect of oestradiol, catechol oestrogens (2- and 4
      hydroxyoestradiol), diethylstilboestrol, PGE2 and PGF2 alpha on basal and human
      chorionic gonadotrophin (hCG) stimulated progesterone production in vitro. The
      role of PGs as modulators of luteal cell function was further investigated by
      studying the metabolic fate of radioactively labelled arachidonic acid in hormone
      treated (oestradiol and hCG) and control cultures, assessed by high performance
      liquid chromatography. PATIENTS: Corpora lutea were enucleated from nine women
      with regular ovulatory cycles undergoing microsurgical reversal of tubal
      sterilization. Granulosa cell aspirates were obtained from three patients
      undergoing in-vitro fertilization treatment. RESULTS: PGE2 and PGF2 alpha at
      various concentrations did not have a consistent effect, whereas oestradiol,
      diethylstilboestrol (and 2-hydroxyoestradiol in early luteal cell cultures)
      significantly inhibited basal and hCG stimulated progesterone biosynthesis.
      Evidence for direct inhibition of 3 beta-hydroxysteroid dehydrogenase enzymic
      activity by oestradiol was obtained. Both major metabolic pathways of arachidonic
      acid (lipoxygenase and cyclo-oxygenase) were operative in steroidogenic luteal
      cells recovered throughout the luteal phase. The ratio of PGE2 to PGF2 alpha
      synthesis in vitro by human luteal cells from endogenously incorporated
      arachidonic acid did not change significantly with corpus luteum age, with PGE2
      tending to predominate. Oestradiol treatment shifted arachidonic acid metabolism
      from the lipoxygenase towards the cyclooxygenase pathway in cells isolated from
      ageing corpora lutea. CONCLUSIONS: Oestradiol, at relatively high concentrations,
      is a potent inhibitor of basal and hCG induced luteal cell steroidogenesis in
      vitro. No support is provided for the concept that luteolysis is mediated by
      local production of PGF2 alpha. The putative luteolytic effect of oestradiol may
      entail reduced metabolism of arachidonic acid to lipoxygenase derived products by
      luteal cells rather than direct stimulation of prostaglandin production by
      itself.

PMID- 8306478
TI  - The effect of oestradiol implants on regional and total bone mass: a three-year
      longitudinal study.
AB  - OBJECTIVE: Although there is evidence from cross-sectional studies that
      percutaneous oestrogen administration protects against menopausal bone loss, few
      longitudinal data are available. We have examined the effect of 3 years'
      treatment with percutaneous oestradiol on total body calcium, spinal trabecular
      bone mineral density and radial bone mineral content in post-menopausal women.
      DESIGN AND PATIENTS: Twenty-nine post-menopausal women, aged 37-55 years, who had
      undergone hysterectomy and had experienced the onset of menopausal symptoms
      within the previous 2 years, were studied before and for 3 years during hormone
      replacement with oestradiol implants, given at approximately 6-monthly intervals.
      MEASUREMENTS: Total body calcium was measured by prompt gamma neutron activation
      analysis, spinal trabecular bone mineral density by quantitative computed
      tomography and radial bone mineral content by single-photon absorptiometry.
      RESULTS: There was a significant increase in the mean total body calcium, spinal
      trabecular bone mineral density and radial bone mineral content over the 3 years
      of the study. The mean (+/- SEM) percentage change per annum was +2.4% (+/- 0.8)
      for total body calcium (P < 0.01), +3.3% (+/- 0.6) for spinal trabecular bone
      mineral density (P < 0.001) and +1.2% (+/- 0.6) for radial bone mineral content
      (P < 0.05). CONCLUSIONS: Percutaneous oestradiol replacement therapy prevents
      menopausal bone loss and is associated with a sustained and significant increase
      in total body calcium, spinal trabecular bone mineral density and radial bone
      mineral content over a 3-year treatment period. Oestradiol implants thus have
      skeletal effects comparable to those of oral or transdermal oestrogens.

PMID- 8306479
TI  - Adrenocorticotrophin stimulation and HLA polymorphisms suggest a high frequency
      of heterozygosity for steroid 21-hydroxylase deficiency in patients with Turner's
      syndrome and their families.
AB  - OBJECTIVE: Following the chance observation of congenital adrenal hyperplasia in
      a patient with Turner's syndrome we decided to evaluate the incidence of 21
      hydroxylase deficiency (21-OHD) in patients with Turner's syndrome and in their
      relatives. SUBJECTS: Fifty-two patients with Turner's syndrome (mean age +/- SD
      14.7 +/- 5.6 years) and 26 relatives were studied. MEASUREMENTS: 17
      Hydroxyprogesterone (17-OHP) serum levels before and after i.m. administration of
      0.25 mg of ACTH(1-24) were evaluated in patients with Turner's syndrome and
      relatives. In Turner patients basal testosterone and dehydroepiandrosterone
      concentrations were determined. The results of ACTH tests were analysed according
      to HLA class I and II alleles of subjects. RESULTS: The baseline 17-OHP was in
      the range of the classical form of 21-OHD in one Turner patient, who had severe
      clitoral enlargement since birth. In 11 patients the stimulated 17-OHP serum
      level was higher than in normal controls and similar to that found in 21-OHD
      heterozygous subjects. Clitoral enlargement was significantly more frequent in
      patients with high stimulated 17-OHP levels (P < 0.001). The frequency of
      heterozygous-type responses was higher in Turner subjects (1:4.6) than in the
      Italian population (1:47 for the classic form and 1:9.5 for the non-classic form
      of the disease). In our patients the frequencies of HLA antigens and haplotypes,
      usually associated with 21-OHD, were different compared to the controls. HLA-B8,
      which is negatively associated to 21-OHD, was less frequent in Turner patients
      than in controls and absent in those with an elevated 17-OHP level. HLA-B14, B22
      and B35 were more frequent, though not significantly so, in Turner patients than
      in controls and even more so in the group with an elevated 17-OHP level. The same
      investigations performed in 26 relatives of the Turner patients showed a high
      frequency of carriers of 21-OHD and three subjects with the cryptic form of the
      disease. CONCLUSIONS: Although in the literature there are only two reports of
      the association of Turner's syndrome and 21-OHD, on the basis of our experience
      this association was more frequent, in the Italian population. Since some of the
      typical signs of 21-OHD (short final stature, varying degrees of virilization,
      menstrual irregularities, amenorrhoea, infertility) in patients with Turner's
      syndrome could also be attributed to the chromosomal abnormality, it is therefore
      more difficult to diagnose 21-OHD in Turner subjects. Adrenal function should be
      assessed, at least in the presence of clitoral enlargement, in patients with
      Turner's syndrome, particularly if their karyotype does not contain a Y
      chromosome. The hypothesis of the presence of cryptic Y chromosome material in
      these patients should also be considered.

PMID- 8306480
TI  - Impaired glucose tolerance and insulin insensitivity in primary
      hyperparathyroidism.
AB  - OBJECTIVE: A high prevalence of diabetes mellitus has been shown in patients with
      primary hyperparathyroidism (PHPT). However, it is unclear whether this is
      related to the metabolic abnormalities in PHPT or to the presence of other risk
      factors for glucose intolerance in these patients. The aim of our study was to
      determine whether glucose intolerance and insulin insensitivity occur in subjects
      with PHPT who do not have other risk factors for diabetes mellitus. DESIGN: Cross
      sectional study of glucose metabolism in PHPT patients without other risk factors
      for diabetes mellitus, compared to age and body mass index (BMI) matched healthy
      subjects. SUBJECTS: Nineteen non-obese, non-diabetic, normotensive patients with
      PHPT and 11 age and BMI matched healthy subjects. MEASUREMENTS: The continuous
      infusion of glucose test was used to assess glucose tolerance. Plasma glucose and
      insulin were measured during a 1-hour continuous infusion of glucose (5 mg/kg
      ideal body weight/min); insulin sensitivity and beta-cell function were derived
      from the glucose and insulin data by mathematical modelling. Fasting serum
      concentrations of parathyroid hormone, ionized calcium and 1,25-dihydroxyvitamin
      D (1,25(OH)2D) were measured in all subjects. RESULTS: PHPT patients attained
      higher plasma glucose levels at the end of the glucose infusion (median 9.0
      (interquartile range 8.1-9.8) mmol/l) than did controls (7.9 (7.1-8.9) mmol/l, P
      < 0.05), and 8 (42%) PHPT patients had impaired glucose tolerance. Insulin
      sensitivity was lower in PHPT (60.3% (49.8-85.4)) than in controls (113.7% (89.3
      149.2), P < 0.001); beta-cell function was not different in PHPT subjects. PHPT
      subjects with impaired glucose tolerance had reduced beta-cell function compared
      to PHPT subjects with normal glucose tolerance (89.9% (70.5-106.4) vs 120% (98.8
      156.6) respectively, P < 0.05). No significant correlations were found between
      insulin sensitivity and PTH (rs = -0.21), 1,25(OH)2D (rs = -0.14), ionized
      calcium (rs = -0.11) and inorganic phosphate (rs = 0.34). Beta-cell function did
      not correlate with PTH (rs = 0.15), 1,25(OH)2D (rs = 0.04), ionized calcium (rs =
      0.23) or inorganic phosphate (rs = -0.35). CONCLUSION: Insulin insensitivity is
      present in PHPT even in the absence of hypertension and obesity, and may be the
      cause of glucose intolerance and diabetes. PHPT subjects with reduced beta-cell
      function are more likely to develop glucose intolerance.

PMID- 8306481
TI  - Insulin sensitivity in non-diabetic relatives of patients with non-insulin
      dependent diabetes from two ethnic groups.
AB  - OBJECTIVE: Non-insulin-dependent diabetes is a heterogeneous disorder, the basis
      of which may differ in different ethnic groups. In order to investigate early
      metabolic abnormalities occurring during the development of the condition we
      assessed insulin secretion and insulin action in subjects predisposed to the
      later development of non-insulin-dependent diabetes from two different ethnic
      groups. DESIGN: Subjects were studied on two separate occasions by an oral
      glucose tolerance test and a short insulin tolerance test. PATIENTS: Twenty-four
      glucose-tolerant first-degree relatives of patients with non-insulin-dependent
      diabetes (12 of European and 12 of Asian origin) were compared with 24 ethnically
      matched control subjects with no family history of diabetes. MEASUREMENTS:
      Insulin, proinsulin, glucose and intermediary metabolites were measured during a
      75-g oral glucose tolerance test. Insulin sensitivity was assessed using a 15
      minute insulin tolerance test (0.05 units/kg). RESULTS: Asian relatives compared
      to Asian controls had significantly higher fasting levels of immunoreactive
      insulin (83 +/- 17 vs 40 +/- 6 pmol/l, P < 0.05), which were not due to increased
      proinsulin. Blood glycerol concentrations were elevated (83 +/- 9 vs 51 +/- 4
      mumol/l, P < 0.005), but fasting glucose and non-esterified fatty acid (NEFA)
      concentrations were similar. Relatives of European origin did not differ from
      their European controls in any of these measurements. The glucose response to
      oral glucose was similar in relatives and controls, irrespective of ethnic group.
      The insulin responses were non-significantly greater in relatives from both
      ethnic groups. Proinsulin levels were not significantly different. Asian
      relatives had higher circulating glycerol and NEFA levels after oral glucose than
      Asian controls, but these differences were not observed in the European group.
      Insulin sensitivity was reduced in the Asian relatives compared to their controls
      (183 +/- 7 vs 139 +/- 12 mumol/l/min, P < 0.01) but there was no difference in
      insulin sensitivity between the European relatives and European controls (167 +/-
      11 vs 160 +/- 11 mumol/l/min). CONCLUSIONS: First-degree relatives of non-insulin
      dependent diabetic patients of Asian, but not of European, origin are insulin
      insensitive in terms of both glucose metabolism and lipolysis, and have true
      hyperinsulinaemia. This suggests that insulin insensitivity may be an early
      abnormality in the development of non-insulin-dependent diabetes in the Asian
      population.

PMID- 8306482
TI  - The HLA association with Graves' disease is sex-specific in Hong Kong Chinese
      subjects.
AB  - OBJECTIVE: Graves' disease is associated with different HLA genes in Caucasians
      and the Chinese, in whom the HLA associations may be stronger in males than
      females. Common HLA-associated susceptibility in both races may occur at the HLA
      DQ loci. The aims of this study were to examine the HLA-A, B, DR and DQ
      associations with Graves' disease in a Hong Kong Chinese population and to
      determine whether the HLA associations differ between the sexes and between
      subjects with and without thyrotoxic periodic paralysis. DESIGN: HLA-A, B and DR
      types were determined by serological typing and DQA1 and DQB1 alleles by
      oligonucleotide probing of the respective enzymatically amplified gene. PATIENTS:
      Ninety-seven Chinese patients with Graves' disease (31 males with, 35 males
      without and 31 females without thyrotoxic periodic paralysis) and 105 racially
      matched healthy controls. MEASUREMENTS: Frequencies of HLA types/alleles at each
      locus were compared between patients and controls and between the Graves'
      subgroups using the chi 2-test. RESULTS: HLA-B46, DR9 and DQB1*0303 were
      associated with Graves' disease in males only; these associations were weaker in
      males with thyrotoxic periodic paralysis. DR12, DQA1*0401 and DQB1*0301 were
      protective, regardless of sex or the presence of thyrotoxic periodic paralysis.
      The positive HLA associations in the Hong Kong Chinese were distinct from those
      in Caucasians whereas the protective haplotype was similar to that described in
      Caucasians. CONCLUSIONS: These findings call in question the role of HLA genes in
      disease susceptibility but suggest a role for HLA in protection from Graves'
      disease.

PMID- 8306483
TI  - Stimulation of extraocular muscle fibroblasts by cytokines and hypoxia: possible
      role in thyroid-associated ophthalmopathy.
AB  - OBJECTIVE: Smoking is a risk factor for the development of thyroid-associated
      ophthalmopathy, an inflammatory process primarily affecting the fibroblasts in
      extraocular muscles. We wished to determine whether the extraocular muscle
      fibroblasts are more sensitive than dermal fibroblasts to T-cell derived
      cytokines, as a reason for this anatomical localization, and whether hypoxia
      alters fibroblast function, as one explanation for the susceptibility conferred
      by smoking. DESIGN: Fibroblasts derived from the skin or extraocular muscles of
      healthy subjects were cultured with cytokines under normal (5% CO2:95% air) and
      hypoxic (5% CO2:95% N2) conditions. MEASUREMENTS: Glycosaminoglycan, protein and
      DNA synthesis were measured by assessing incorporation of D-6-3H-glucosamine, 3H
      amino acids, and 3H-thymidine respectively. RESULTS: alpha-interferon and
      interleukin-6 had no effect on fibroblasts. gamma-interferon, tumour necrosis
      factor and interleukin-1 stimulated glycosaminoglycan synthesis; this effect was
      greater in orbital than in dermal fibroblasts with gamma-interferon and
      interleukin-1 (P < 0.05). The same cytokines stimulated total protein with a
      greater response in orbital fibroblasts with gamma-interferon. Interleukin-1
      inhibited DNA synthesis in orbital fibroblasts but stimulated DNA synthesis in
      dermal fibroblasts (P < 0.01); tumour necrosis factor also displayed a
      differential effect (P < 0.01). Hypoxia caused a significant increase in
      glycosaminoglycan, protein and DNA synthesis in both types of fibroblasts, under
      both basal and cytokine-treated conditions (P < 0.05). CONCLUSIONS: Extraocular
      muscle fibroblasts respond differently from dermal fibroblasts following cytokine
      stimulation, which may explain in part the anatomical localization of
      ophthalmopathy. Hypoxia stimulates fibroblasts and this could contribute, as an
      enhancing factor, to the adverse effects of smoking on thyroid eye disease.

PMID- 8306484
TI  - The effect of low and high sodium diets on plasma atrial natriuretic factor, the
      renin-aldosterone system and blood pressure in subjects with essential
      hypertension.
AB  - OBJECTIVE: Increasing dietary sodium intake increases blood pressure in some
      subjects with essential hypertension. Atrial natriuretic factor (ANF) has a
      potential role in modifying these changes. The purpose of this study was to
      observe the blood pressure and plasma ANF responses to low and high sodium diets
      in subjects with essential hypertension to see if the plasma ANF and blood
      pressure responses were related. DESIGN: An in-patient study of subjects taking
      their normal diet (day 1), a 12 mmol sodium diet for 6 days and a 250 mmol diet
      for 6 days. PATIENTS: Seven men with essential hypertension. MEASUREMENTS:
      Continuous 24 hour urine collections were analysed for sodium excretion. Blood
      pressure was recorded at 0900, 1205 and 1700 h on days 1, 7 and 13. Blood was
      taken at 0900 h (fasting supine overnight) and at 1200 h (after 2 hours erect
      posture) on the above days for plasma ANF, plasma renin activity (PRA) and serum
      aldosterone. RESULTS: Urinary sodium excretion was (mean +/- SEM) 11 +/- 1 mmol
      on day 5 of the low sodium diet, and 294 +/- 17 mmol during the fifth day of the
      high sodium diet. Plasma ANF (supine and erect) was significantly lower (2.8 +/-
      0.6, 1.6 +/- 0.2 pmol/l) on the low sodium diet when compared to the high sodium
      diet (8.6 +/- 2.4, 5.0 +/- 1.6 pmol/l (P < 0.05)). Supine and erect PRA and serum
      aldosterone were significantly higher on the low compared to the high sodium
      diet. Blood pressure responses were heterogeneous rather than bimodal. Mean
      arterial blood pressure was 107 +/- 3 mmHg on the low sodium diet and 111 +/- 4
      mmHg on the high sodium diet (P < 0.05). Changes of blood pressure did not
      correlate with the changes of plasma ANF. CONCLUSIONS: Failure of plasma atrial
      natriuretic factor to rise with increasing dietary sodium did not therefore
      determine the blood pressure response to the change in dietary sodium. No link
      was established between plasma atrial natriuretic factor response and sodium
      sensitivity.

PMID- 8306485
TI  - Transport of thyroxine into cultured hepatocytes: effects of mild non-thyroidal
      illness and calorie restriction in obese subjects.
AB  - OBJECTIVE: Inhibitors of cellular T4 transport leading to diminished plasma T3
      production have been identified as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic
      acid (CMPF) and indoxyl sulphate in uraemia and bilirubin and non-esterified
      fatty acids (NEFA) in critically ill patients with hyperbilirubinaemia. We
      question whether other factors are responsible for the altered thyroid hormone
      parameters observed in mild illness and during calorie restriction. PATIENTS: We
      studied (i) 18 non-uraemic patients with non-thyroidal illness (NTI) (T4 > or =
      60, T3 < or = 1.1 and rT3 > or = 0.45 nmol/l) with serum molar ratios of
      bilirubin:albumin < or = 0.17 and NEFA:albumin < or = 2.6. These molar ratios
      have been shown to be the minimum ratios which inhibited T4 transport into rat
      hepatocytes; (ii) four obese euthyroid subjects on 600 kcal/day for 10-14 days.
      This diet is known to inhibit the unidirectional T4 transport into human liver in
      vivo. MEASUREMENTS: We measured iodide production from 125I-T4 by incubating rat
      hepatocytes with 10% human serum. The deiodination of T4 was used as an index of
      cellular transport of T4 in vivo. RESULTS: The mean iodide production from 125I
      T4 by rat hepatocytes in the presence of 10% serum from NTI patients (98 +/- 17%,
      mean +/- SD) was not significantly different from the normals (100 +/- 9%).
      Calorie restriction in euthyroid obese subjects resulted in a small but
      significant reduction (-12%) of iodide production. Calorie restriction increased
      the total serum NEFA by 91%. CONCLUSIONS: Our study demonstrates that CMPF,
      indoxyl sulphate, bilirubin and NEFA are not responsible for the inhibition of T4
      tissue uptake in patients with mild illness. In addition, studies with calorie
      restricted obese subjects indicate that high concentration of NEFA during calorie
      restriction inhibits T4 tissue uptake. This inhibition may partly explain the
      lower plasma T3 during calorie restriction.

PMID- 8306487
TI  - Pyridostigmine induced growth hormone release in mania: focus on the
      cholinergic/somatostatin system.
AB  - OBJECTIVE: The release of growth hormone (GH) from the anterior pituitary is
      partly under cholinergic control. Pyridostigmine, the acetylcholinesterase
      inhibitor, releases GH by this mechanism. Pyridostigmine/GH responses have been
      reported as enhanced in depression. The aim of the current study was to examine
      such responses during a manic episode. DESIGN: A between subjects design was
      employed. SUBJECTS: Seven male manic patients and seven male healthy controls
      were studied. They were matched in terms of age and body mass index.
      MEASUREMENTS: GH response to pyridostigmine (120 mg) challenge was measured as
      the net increase above baseline. Cortisol levels were also measured. RESULTS:
      Release of GH in the manic patients was significantly enhanced and their baseline
      cortisol levels were elevated. CONCLUSIONS: These results demonstrate enhanced
      pyridostigmine/GH responsiveness in mania which may be due to enhanced
      somatostatin tone or increased cholinergic receptor responsivity.

PMID- 8306486
TI  - Pituitary tumour localization in patients with Cushing's disease by magnetic
      resonance imaging. Is there a place for petrosal sinus sampling?
AB  - OBJECTIVE: We wished to analyse the relative value and diagnostic accuracy of
      bilateral simultaneous inferior petrosal sinus blood sampling for plasma ACTH
      measurements when compared with pituitary magnetic resonance imaging (MRI) for
      the preoperative localization of microadenoma (tumour diameter < 10 mm) within
      the pituitary fossa in patients with Cushing's disease. DESIGN: Pituitary MRIs
      were assessed blind and independently. The sinus blood sampling was performed
      before and after administration of corticotrophin releasing hormone (CRH). The
      ratios of the ACTH concentrations in plasma samples from the inferior petrosal
      sinuses to the concentrations in peripheral blood plasma samples (the IPS:P
      ratio) and the ratios of the ACTH concentrations in samples from both inferior
      petrosal sinuses (the intersinus gradient) were calculated. PATIENTS: Twenty
      consecutive patients with Cushing's disease were prospectively studied. All but
      two patients subsequently underwent transsphenoidal exploration of the pituitary
      fossa. RESULTS: In three of 20 patients (15%), positioning of catheter tips in
      both inferior petrosal sinuses was unsuccessful. The diagnosis of Cushing's
      disease was confirmed by the greater basal IPS:P ratio amounting to > or = 2.0 in
      13 of 17 patients (76%), and amounting to > or = 3.0 in CRH-stimulated peak
      samples in 15 of 17 patients (88%). Anatomical variations of the inferior
      petrosal sinus, precluding reliable conclusions about lateralization of pituitary
      venous ACTH drainage, were observed in five of 20 patients (25%). Adding the
      three patients with technical failure and one patient who presented with a
      macroadenoma (tumour diameter 11 mm), this left interpretable data with regard to
      lateralization of the microadenomas in only 11 of 20 patients (55%). In 15 of 20
      patients (75%) a pituitary microadenoma was found at MRI. In 14 of these 15
      patients (93%) a tumour was indeed found at that position at subsequent
      transsphenoidal operation. Concordance between the lateralization by the
      intersinus gradient and microadenoma localization by MRI was observed in six of
      11 cases (55%) when using basal samples and in seven of 11 cases (64%) when using
      peak samples obtained after stimulation with CRH. Concordance between the
      lateralization by the intersinus gradient and subsequent microadenoma
      localization at surgery was observed in seven of 11 patients (64%) before and in
      eight of 11 cases (73%) after CRH stimulation. Reversal of the intersinus
      gradient after CRH stimulation, suggesting a shift in the lateralization to the
      contralateral side of the gland, was found in three of 12 cases (25%).
      CONCLUSIONS: Bilateral simultaneous inferior petrosal sinus blood sampling for
      plasma ACTH measurements before and after CRH stimulation successfully confirmed
      the diagnosis of pituitary dependent Cushing's disease in 15 of 17 patients (88%)
      in whom this diagnosis was suspected on the basis of conventional biochemical
      testing. Magnetic resonance imaging, however, is superior to bilateral
      simultaneous inferior petrosal sinus blood sampling for the
      localization/lateralization of pituitary microadenomas in patients with Cushing's
      disease. Therefore, bilateral simultaneous inferior petrosal sinus blood sampling
      should be reserved for the assessment of those patients with Cushing's syndrome
      in whom either the results of biochemical tests are equivocal and/or subsequent
      pituitary magnetic resonance imaging gives unconvincing results.

PMID- 8306488
TI  - Growth hormone releasing hormone 1-44 NH2 and 1-40 OH levels in normal subjects
      during growth hormone stimulation tests.
AB  - OBJECTIVE: Little is known about the relative circulating concentrations of
      growth hormone releasing hormone (GHRH) 1-44 NH2 and 1-40 OH in response to
      dynamic GH stimulation. We therefore studied the concentrations of growth hormone
      releasing hormone (GHRH) 1-44 NH2 and 1-40 OH in the peripheral plasma of normal
      male subjects during GH stimulation tests. DESIGN: Tests were performed at 0900 h
      after an overnight fast. Stimulation tests, commenced at 0 minutes, included
      alpha-adrenergic activation with adrenaline (10 micrograms/min from 0 to 30
      minutes) following beta-blockade with propranolol (1.5 mg/min from -10 to 0
      minutes), alpha 2-adrenergic activation with clonidine 150 micrograms i.v.,
      insulin hypoglycaemia (0.15 U/kg soluble insulin), L-arginine infusion (30 g from
      0 to 30 minutes), L-dopa (500 mg orally) and oral glucose (100 g). SUBJECTS:
      Groups of healthy male volunteers aged 20-42 years, all within 10% of ideal body
      weight. MEASUREMENTS: Serum GH and plasma GHRH 1-44 NH2 and 1-40 OH were measured
      at intervals for between 60 and 390 minutes, depending on the stimulation test.
      RESULTS: There were no significant changes in either GHRH 1-44 or 1-40 following
      alpha-adrenergic activation with propranolol/adrenaline infusion, alpha 2
      adrenergic activation with i.v. clonidine, insulin-induced hypoglycaemia or
      arginine infusion despite the expected rise in GH levels. After oral glucose, GH
      was initially suppressed with a late rise. There were no changes in GHRH 1-44 or
      1-40 levels during either phase of this response. After L-dopa GH levels peaked
      at 90 minutes, 24.5 +/- 11.0 mU/l (mean +/- SEM). At 0 minutes GHRH 1-44 and 1-40
      levels were 3.25 +/- 0.89 and 4.93 +/- 1.28 pmol/l respectively and rose in both
      cases, peaking at 60 minutes at 4.23 +/- 1.01 and 7.55 +/- 1.80 pmol/l (P <
      0.05). At no time was there any evidence of differential secretion of GHRH 1-44
      or 1-40. CONCLUSIONS: We have confirmed previous studies demonstrating a small
      rise in GHRH before the GH response to L-dopa. However, in all other situations
      of pharmacological stimulation of GH release we were unable to detect any
      significant changes in GHRH 1-44 or 1-40 levels. It seems most likely that
      peripheral GHRH does not reflect hypothalamic secretion. As yet there is no
      evidence for differential release of GHRH 1-44 and 1-40.

PMID- 8306489
TI  - Can the risk of colon cancer be lessened?
AB  - Colon cancer was rare or uncommon in the past, and still is in traditionally
      living third world populations. It now affects 3-5% of western populations.
      Epidemiological, case control, experimental and other studies suggest that
      proneness to colon cancer can be lessened by major dietary changes, principally
      decreasing fat intake by a third, and doubling the intake of fiber-containing
      foods, especially vegetables and fruit--recommendations similarly advocated for
      the avoidance of coronary heart disease and other degenerative diseases. Among
      nondietary factors, evidence indicates familiality, obesity and atmospheric
      pollution to be contributory, while parity, physical activity, solar radiation,
      high social class, estrogen use, and aspirin use, appear protective. Despite
      insufficiencies of knowledge of prevention, avoiding action should certainly be
      taken by those familially prone. For the rest, conceivably a prudent life-style
      could benefit a proportion avoiding colon cancer.

PMID- 8306490
TI  - Pharmacotherapy of inflammatory bowel disease.
AB  - The standard treatments for inflammatory bowel disease have been aminosalicylates
      and corticosteroids, administered both systemically and topically. They are
      frequently extremely effective, especially at higher doses. Unfortunately steroid
      side effects are too frequent and agents with low systemic bioavailability
      (budesonide, beclamethasone and tixocortol) are being investigated. Azathioprine,
      although a useful adjunct to steroids, has occasional and unpredictable severe
      side effects. Cyclosporin is an important new therapy in severe refractory
      disease. Several new phospholipid mediator inhibitors, mepacrine, zileuton, and
      ridogrel, may be useful in moderate colitis. Other topical treatments, butyrate,
      acetarsol and bismuth subsalicylate, can be beneficial in refractory distal
      disease. Quadruple antimycobacterials, antioxidants and antimicrobials warrant
      further study, while newer immunosuppressives such as methotrexate, FK 506 and
      monoclonal antibodies against helper T lymphocytes show some early promise.

PMID- 8306491
TI  - Prevention of chemotherapy-induced emesis: the state of the art.
AB  - In the last decade research on antiemetic therapy has determined relevant
      advances in the prevention of chemotherapy-induced emesis. In fact, 70-80% of
      patients submitted to highly or moderately emetogenic drugs achieve complete
      protection against vomiting during the first cycle of chemotherapy. In the
      prevention of acute emesis induced by a high single dose (> or 50 mg/m2) or a low
      dose (20-40 mg/m2) of cisplatin repeated for 4-5 days, a combination of
      ondansetron plus dexamethasone was shown to be more efficacious and less toxic
      than the combination of high dose metoclopramide plus dexamethasone plus
      diphenhydramine. Few studies have been performed for the prevention of delayed
      emesis induced by cisplatin. At present, the combination of oral dexamethasone
      plus metoclopramide seems to offer the best protection and should be considered
      the treatment of choice. For the prevention of acute emesis induced by moderately
      emetogenic drugs, corticosteroids (dexamethasone and methylprednisolone) and the
      new 5-HT3 receptor antagonists have a similar efficacy and a low toxicity. On a
      cost basis, corticosteroids must be considered the drug of choice while 5-HT3
      receptor antagonists should be used only in patients refractory to
      corticosteroids or in those who cannot tolerate them.

PMID- 8306492
TI  - Esophageal pH monitoring of postprandial gastroesophageal reflux. Comparison
      between healthy subjects, patients with gastroesophageal reflux and patients
      treated with Nissen fundoplication.
AB  - To analyze postprandial gastroesophageal reflux by means of ambulatory
      gastroesophageal pH monitoring for 24 h, four groups were studied prospectively:
      group A: 22 healthy volunteers; group B: 31 consecutive patients undergoing
      medical treatment for gastroesophageal reflux, group C1: 20 consecutive patients
      with symptomatic reflux awaiting surgical treatment by means of Nissen
      fundoplication (pre-Nissen evaluation) and group C2: group C1 patients
      reevaluated 6 months postoperatively (post-Nissen evaluation). Gastro-esophageal
      pH, as a measure of post-prandial reflux following the main meal of the day was
      evaluated by the Kaye test. In groups B, C1 and C2, esophageal manometry was also
      performed. Gastroesophageal pH monitoring revealed significant qualitative as
      well as quantitative differences in postprandial gastroesophageal reflux
      experienced by healthy subjects (group A) and surgically treated patients (group
      C2) compared to patients with pathologic reflux (groups B and C1). The
      postprandial reflux was significantly more acid and more important (Kaye's test
      value) in groups C1 and B than in groups A and C2. There were no differences in
      postprandial reflux between healthy subjects and patients treated by Nissen
      fundoplication (group C2). Only the pressure and length of the lower esophageal
      sphincter (LES) showed differences after Nissen fundoplication. We conclude that
      patients with pathologic reflux have more severe postprandial reflux than normal
      subjects; Nissen fundoplication corrects the degree of postprandial reflux to a
      normal range by elevating the LES pressure (11.3 x 1.4 vs. 22.4 +/- 1.6 mm Hg; p
      < 0.001) and length (2.7 +/- 0.2 vs. 3.7 +/- 0.1 cm; p < 0.001) in our patients.

PMID- 8306493
TI  - The costimulatory signal CD28 is fully functional but cannot correct the impaired
      antigen response in T cells of patients with common variable immunodeficiency.
AB  - A wide spectrum of different immunologic abnormalities have been postulated as
      being responsible for the impairment of specific antibody production and the
      decrease in all or selected immunoglobulin isotypes present in common variable
      immunodeficiency (CVID). These abnormalities include impaired B cell
      differentiation and/or function, defective macrophage function, and significant T
      cell defects. The aim of the present study was to delineate whether the accessory
      molecule CD28 is involved in the impaired antigen response of T cells from
      patients with CVID. Our results demonstrate that CD28 costimulation was
      functional in T cells stimulated with anti-CD3 or anti-TCR MoAb, but could not
      correct the impaired response of patients' peripheral blood T cells to tetanus
      toxoid. Analysis of patients' long-term cultured T cells further confirmed these
      results. Exogenous rIL-2, another costimulus, augmented but did not correct the
      defective proliferation and lymphokine production in patients' antigen-driven
      peripheral blood T lymphocytes or in long-term cultured T cells. These findings
      indicate that the CD28 signalling pathway in these patients' T cells is
      unimpaired, and that costimulation via CD28 cannot correct the defect occurring
      in the course of TCR-mediated T cell activation.

PMID- 8306494
TI  - Intestinal B cell defects in common variable immunodeficiency.
AB  - The humoral immune system of the small intestine of 17 patients with common
      variable immunodeficiency (CVID) was studied by immunohistology using antibodies
      specific for IgA1,2, IgM, IgG1-4, the J chain and the secretory component (SC).
      IgA1,2+, IgG2+ and IgM+ lamina propria B cells were totally lacking in 65%
      (11/17), 41% (7/17) and 18% (3/17) of CVID patients, respectively. One patient
      exhibited an isolated IgA1 subclass deficiency. The proportion of plasma cells in
      conventionally stained histological sections of the same intestinal biopsies
      showed a close correlation with the numbers of IgA+ and IgM+ cells. Considerable
      numbers of J chain-synthesizing cells were present in all patients with CVID,
      indicating the presence of early B cells unable to differentiate into
      immunoglobulin-producing plasma cells. Most of the patients with intestinal IgA
      and/or IgM defects strongly expressed the SC in their enterocytes, suggesting an
      immunoglobulin-independent regulation of the SC. Clinically, only CVID patients
      with intestinal IgA defects developed intestinal infections with Giardia lamblia,
      Campylobacter jejuni or Candida albicans. The outcome of in vitro immunoglobulin
      synthesis assays with peripheral blood lymphocytes did not predict the presence
      or absence of the respective isotype-producing B cells in the intestinal lamina
      propria. Thus, immunohistological examinations of intestinal biopsies are
      required to determine the extent of mucosal immunodeficiency in CVID patients.

PMID- 8306495
TI  - Intestinal and circulating antibody-forming cells in IgA-deficient individuals
      after oral cholera vaccination.
AB  - In search for a possible explanation for the different susceptibility to mucosal
      infections in IgA-deficient (IgAd) individuals, the frequency of total
      immunoglobulin-secreting cells (ISC) and vaccine-specific antibody-secreting
      cells (ASC) in intestinal mucosa and peripheral blood was determined by the
      enzyme-linked immunospot (ELISPOT) assay before and after peroral vaccination
      with a B subunit-whole cell cholera vaccine. Two groups of IgAd individuals,
      frequently infected and non-infected respectively, and normal controls were
      studied. Before cholera vaccination there were significantly higher frequencies
      of total IgM and IgG ISC in the gut, but not in the blood, in the IgAd
      individuals than in the controls. However, there were no significant differences
      between healthy and infection-prone IgAd individuals in this respect. In response
      to oral cholera vaccination, intestinal cholera toxin (CT)-specific IgG and IgM
      ASC were significantly more abundant among the IgAd individuals with a history of
      frequent infections than among the healthy IgAd individuals and controls. A
      similar difference in IgG and IgM ASC, although not significant, was also noted
      in blood. In IgAd individuals with frequent infections the vaccine induced
      variable anti-CT IgM ASC responses in the gut, ranging from no increase to a few
      strikingly high responses. In the controls, the CT-specific responses were
      dominated by IgA ASC. The data show that oral cholera vaccination evoked strong
      CT-specific IgG ASC responses, and in some cases also strong IgM ASC responses in
      the intestinal mucosa of IgAd patients with a history of frequent infections. The
      healthy IgAd individuals unexpectedly responded with lower numbers of CT-specific
      IgG ASC and did not show any increase of CT-specific IgM ASC in the intestinal
      mucosa. Thus, inability to mount a mucosal immune response to an oral antigen
      cannot in itself explain recurrent infections among many IgAd individuals.

PMID- 8306496
TI  - Processing and presentation of tetanus toxin by antigen-presenting cells from
      patients with chronic granulomatous disease (CGD) to human specific T cell clones
      are not impaired.
AB  - The capacity of peripheral blood lymphocytes (PBL) or Epstein-Barr virus (EBV)
      transformed B cell lines from CGD patients to process and present tetanus toxin
      (tt)-specific epitopes was assessed using various tt preparations and human tt
      specific T cell clones. PBL from all of the donors were able to process and
      present either native tt and/or denatured tt to human T cell clones specific for
      various tt epitopes. Furthermore, no difference was found in the antigen
      requirement when normal or CGD EBV-B cell lines were used as antigen-presenting
      cells (APC). These results suggest that the deficiency in oxygen metabolism in
      CGD cells does not affect tt processing and presentation.

PMID- 8306497
TI  - Follow up of soluble IL-2 receptor level in metastatic malignant melanoma
      patients treated by chemoimmunotherapy.
AB  - Immunological parameters following chemoimmunotherapy combination were studied in
      31 patients with metastatic malignant melanoma. They received Cisplatin (100
      mg/m2) on day 1 and 28, recombinant IL-2 (rIL-2; Eurocetus) in continuous
      infusion from day 3 to 6, 17 to 21, 31 to 34 and 45 to 49. Interferon-alpha (IFN
      alpha; Roche) was given subcutaneously three times weekly. No significant change
      in CD4/CD8 ratio at onset or during treatment was observed between responder (n =
      19) and non-responder (n = 12) patients. Regarding the IL-2 receptor (IL-2R)
      study, the percentage of cells expressing Tac (p55) receptor did not change
      either for healthy volunteers (n = 20) and patients before any therapy, or
      between responder and non-responder patients. Concerning serum soluble IL-2R
      shedding before therapy, we observed a significant increase (P = 0.001) in
      patients (79 +/- 40 pM) compared with healthy donors (30 +/- 15 pM), but no
      significant variation was seen between responder and non-responder patients. In
      contrast, during the treatment, the soluble IL-2R level increased in both groups
      but, interestingly, a significant difference was found between responder and non
      responder patients from day 7 (P < 0.05) to day 21 (P < or = 0.01), suggesting
      that the cells from non-responder may be slower in becoming stimulated. This
      finding is the most striking point of our study and suggests that sIL-2R might be
      an early predictive factor of the clinical response as obtained by logistic
      regression (P = 0.0063). Therefore patients with a serum soluble IL-2R level
      greater than 250 pM at day 21 have a 12-fold more chance of undergoing a clinical
      response.

PMID- 8306498
TI  - Amelioration of established murine collagen-induced arthritis with anti-IL-1
      treatment.
AB  - Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid
      arthritis. To validate a key role for IL-1 in arthritic processes we have studied
      the protective effect of neutralizing antimurine IL-1 antibodies in the murine
      collagen-induced arthritis (CIA) model. Combination of anti-IL-1 alpha and anti
      IL-1 beta given before onset of arthritis was shown to prevent disease
      completely. Remarkably, a single treatment was also highly effective in the
      established phase of arthritis, reducing both inflammation as well as cartilage
      destruction. Suppression was most pronounced with the combination, but anti-IL-1
      beta alone also induced significant relief. Finally, we studied the protective
      effect of IL-1 neutralization on cartilage metabolism in a unilateral expression
      model of collagen arthritis. To this end zymosan was injected in one knee joint
      before onset of disease, resulting in accelerated expression in that particular
      joint and the draining paw. Anti-IL-1 treatment started after accelerated
      expression of arthritis was able to fully normalize chondrocyte synthetic
      function, which was highly suppressed in the control group. It is concluded that
      IL-1 is an important determinant in both inflammation and cartilage destruction
      in collagen arthritis, and this may have implications for therapy in human
      arthritis.

PMID- 8306499
TI  - Activated neutrophils express proteinase 3 on their plasma membrane in vitro and
      in vivo.
AB  - Apart from the diagnostic value of anti-neutrophil cytoplasmic antibodies (ANCA),
      their detailed characterization and that of their corresponding antigens have
      opened new ways for the exploration of the pathogenesis of primary systemic
      vasculitis. ANCA are now thought to play an important functional role via
      activation of phagocytic cells (e.g. polymorphonuclear neutrophils (PMN)). In
      this study we examined the mechanisms by which ANCA could gain access to
      proteinase 3 (PR3) in intact PMN, at two levels: ex vivo by analysing the
      presence of PR3 on the plasma membrane of PMN from patients with ANCA-associated
      vasculitis, and in vitro by stimulation of PMN using different cytokines,
      including recombinant tumour necrosis factor-alpha (rhTNF-alpha) and two forms of
      IL-8 (produced by monocytic and endothelial cells). Using immunocytochemical
      staining techniques (FACS and immunoelectronmicroscopy) PR3 has been detected on
      the plasma membrane of PMN from patients with active ANCA-associated vasculitis.
      However, this phenomenon is also seen in patients with sepsis who do not have
      ANCA. In addition, TNF-alpha and both forms of IL-8 act synergistically and
      induce a translocation of PR3 from the intragranular loci to the cell surface of
      PMN. These results provide strong evidence for the hypothesis that ANCA are
      directly pathogenic by binding to PR3 which is expressed on the cell surface of
      primed/activated PMN.

PMID- 8306500
TI  - Anti-proteinase 3 antibodies, their characterization and disease associations.
AB  - Anti-proteinase 3 antibodies are a subgroup of anti-neutrophil cytoplasmic
      antibodies (ANCA), and we have established an ELISA for their detection using
      high performance liquid chromatography (HPLC)-purified protein. This assay is
      sensitive and specific: inhibition studies have shown that despite the homology
      between proteinase 3 and elastase there is no cross-reactivity between the
      corresponding antibodies for their targets. Anti-proteinase 3 antibodies were
      associated most often with cytoplasmic fluorescence (17/22, 77%), but
      occasionally with a perinuclear (3/22, 14%) or atypical pattern (1/2). These
      antibodies were found in 23 out of 76 sera (30%) that were positive in an ELISA
      based on a crude neutrophil cytoplasmic extract, and they were associated with
      both 29 and 55 kD bands on Western blots. Anti-proteinase 3 antibodies were found
      in most individuals with active Wegener's granulomatosis (10/13, 77%), but less
      often in individuals with microscopic polyarteritis (2/10, 20%) or segmental
      necrotizing glomerulonephritis (3/6, 50%). However, anti-proteinase 3 antibodies
      were not detected in any of 32 sera from individuals with rheumatoid arthritis or
      systemic lupus erythematosus (SLE). Occasionally anti-proteinase 3 antibodies
      were associated with anti-glomerular basement membrane antibodies (1/11, 9%) or
      with anti-myeloperoxidase antibodies (1/11, 9%). IgM anti-proteinase 3 antibodies
      were uncommon (2/22 sera, 9%), and no IgA antibodies were demonstrated in any of
      22 sera from patients with active systemic vasculitis. Significantly more
      individuals presented with anti-proteinase 3 antibodies in April-May-June,
      suggesting that an infective agent prevalent in Autumn might have a causative
      role in the associated diseases. Anti-proteinase 3 antibodies are the most common
      target antigen associated with Wegener's granulomatosis and cytoplasmic
      fluorescence.

PMID- 8306501
TI  - Anti-idiotypic activity against anti-myeloperoxidase antibodies in pooled human
      immunoglobulin.
AB  - We investigated the ability of six different pooled human immunoglobulin (PHIG)
      preparations to inhibit the binding of anti-myeloperoxidase (MPO) antibodies to
      MPO. All six PHIG preparations inhibited the binding of anti-MPO antibodies from
      six sera to MPO in a concentration-dependent manner in the concentration range
      0.016-10 mg/ml. There was considerable variation in the ability of each PHIG
      preparation to inhibit the binding of anti-MPO antibody in a given serum. Further
      differences were seen in the ability of a given PHIG to inhibit anti-MPO binding
      in different sera. F(ab')2 fragments from two PHIG preparations also inhibited in
      a concentration-dependent manner anti-MPO binding to MPO in all six sera in the
      concentration range 0.002-2.65 mg/ml, with a maximum inhibition of 42%. Little
      inhibition was seen with F(ab')2 of normal human IgG from individual donors (1.8
      12.2% at the maximum concentration of 2 mg/ml). F(ab')2 fragments from three anti
      MPO containing sera and two affinity-purified anti-MPO antibodies were eluted by
      affinity chromatography from Sepharose-bound PHIG F(ab')2 and showed anti-MPO
      antibody activity. We have shown that PHIG and F(ab')2 fragments of PHIG inhibit
      anti-MPO binding to MPO, and further that F(ab')2 fragments of PHIG bind to
      F(ab')2 fragments of anti-MPO antibodies. These observations indicate binding
      between the variable regions of PHIG and the antigen binding site of anti-MPO
      antibodies, and are consistent with an anti-idiotypic reaction. The variability
      seen in the inhibitory effect of the different PHIG preparations in anti-MPO
      positive sera implies differences in their anti-idiotype content, while the
      variability of the inhibitory effect of a particular PHIG preparation between
      different sera suggests heterogeneity in the idiotypic repertoire of anti-MPO
      antibodies. Such variations in the inhibitory effect of different PHIG
      preparations on antibody binding may be an important determinant of their
      therapeutic effect.

PMID- 8306502
TI  - Endothelial serpins--protectors of the vasculature?
AB  - Vascular damage, initiated by host inflammatory cells, is a component of the
      pathophysiology of many acute and chronic inflammatory disorders. Neutrophil
      mediated tissue damage is mediated primarily by proteinases, particularly
      elastase and cathepsin G. In this study we have identified endothelial binding of
      two key serine proteinase inhibitors (serpins), alpha 1-antitrypsin, the
      inhibitor of elastase, and alpha 1-antichymotrypsin, the inhibitor of cathepsin
      G. These serpins are shed from the endothelium into the supernatant when
      neutrophils adherent to the endothelium are activated. Endothelium activated by
      lipopolysaccharide (LPS) augments this process. Serpin-proteinase complexes
      activate neutrophils and induce further cytokine release, thereby amplifying
      inflammatory processes. Strategies aimed at preventing endothelial serpin
      depletion may help minimize vascular damage during inflammation.

PMID- 8306503
TI  - High serum levels of soluble CD8 in insulin-dependent diabetes.
AB  - In type 1 (insulin-dependent) diabetes mellitus (IDDM) CD8+ T cells represent the
      majority of lymphocytes which infiltrate the pancreatic islets during beta cell
      destruction. Soluble CD8 antigen (sCD8) has been shown to correlate with CD8 cell
      subset activation. In this study we measured by ELISA sCD8 levels in sera from:
      33 newly diagnosed IDDM patients; 29 type 1 diabetics with duration of disease
      more than 1 year; 37 healthy siblings of IDDM patients; 19 healthy controls. Sera
      from both groups of IDDM patients and from healthy siblings exhibited soluble CD8
      mean levels significantly higher than controls (P = 0.0001, P < 0.003, P < 0.03
      respectively). Soluble CD8 levels above the normal range (mean +/- 2 s.d. of
      controls) were found in a percentage of newly diagnosed subjects (54.5%)
      significantly higher than in subjects with a long-standing duration of disease
      (6.9%, P < 0.0005) and healthy siblings (16.2%, P < 0.002). Our results suggest
      that the raised levels of soluble CD8 near to diabetes onset may indicate the
      activation of CD8+ T cells probably responsible for the autoimmune beta cell
      destruction.

PMID- 8306504
TI  - The significance of blood levels of IgM, IgA, IgG and IgG subclasses in Sudanese
      visceral leishmaniasis patients.
AB  - We developed an ELISA test using leishmania antigenic extracts to detect antigen
      specific antibody responses, including subclass and isotype analysis, in visceral
      leishmaniasis (VL) patients from the Sudan. A total of 92 parasitologically
      proven patients were compared with cutaneous leishmaniasis, schistosomiasis,
      malaria, onchocerciasis and tuberculosis patients, as well as with healthy
      endemic and non-endemic controls. Some VL patients were examined before and after
      chemotherapy. VL patients showed significantly higher IgG responses compared with
      all other groups (93.4% sensitivity, 93.7% specificity), and higher (but not
      significantly) IgM responses. All groups showed low IgA levels. All IgG
      subclasses, IgG1, 2, 3, and 4, showed higher levels in patients than all other
      groups, with IgG1 and IgG3 levels being significantly reduced following
      treatment. The rank order for specificity and sensitivity for IgG subclasses was
      IgG3 > IgG1 > IgG2 > IgG4.

PMID- 8306505
TI  - High levels of circulating IL-10 in human malaria.
AB  - IL-10 is a monocyte/lymphocyte derived cytokine which has been shown to inhibit
      certain cellular immune responses such as delayed hypersensitivity. In
      particular, the production of tumour necrosis factor (TNF), IL-1 and IL-6, which
      are involved in malaria pathology, are strongly inhibited by IL-10. Accordingly,
      we examined whether IL-10 could be involved in a human acute parasitic infection
      such as Plasmodium falciparum malaria. Human IL-10 levels in plasma were
      determined by two-site ELISA method, taking care to avoid non-specific reactions
      due to autoantibodies. Fourteen cerebral, 11 severe, and 20 mild malaria cases
      had mean IL-10 levels of 2812, 2882 and 913 pg/ml, respectively, while 98% of
      healthy individuals had undetectable (less than 100 pg/ml) circulating IL-10.
      Thirteen of the 25 cerebral/severe cases had > 2000 pg/ml. In 11 hospitalized
      patients, circulating IL-10 levels were found to return to virtually normal
      levels 7 days after antimalarial chemotherapy when biological and clinical
      malaria features had disappeared (mean levels fell from 3880 to 333 pg/ml).
      Further studies are required to determine whether these elevated levels of IL-10
      play a beneficial role by reducing the parasite-induced inflammatory response, or
      a detrimental one by decreasing the cellular immune responses.

PMID- 8306506
TI  - High levels of anti-phospholipid antibodies in uncomplicated and severe
      Plasmodium falciparum and in P. vivax malaria.
AB  - The majority (75%) of adult patients with uncomplicated Plasmodium falciparum and
      P. vivax malaria are positive for anti-phospholipid antibodies (aPLA) as
      demonstrated by ELISA using a panel of anionic and cationic phospholipids. The
      highest IgG and IgM binding was to the anionic phospholipids, phosphatidylserine
      (PS), phosphatidic acid (PA) and cardiolipin (CL), but excluding
      phosphatidylinositol (PI) to which only low antibody levels were found.
      Comparison of the mean IgG and IgM aPLA showed a trend for anti-PA > CL > PS > PC
      > PE > PI. Anti-PI levels were compared in two groups of African children, one
      group with non-severe and the other with severe (cerebral) falciparum malaria.
      Children with cerebral disease had significantly lower IgM anti-PI. The results
      are discussed with the view that serum-derived aPLA may have a role in 'anti
      disease' immune responses. Their possible role in the opsonization and
      phagocytosis of parasitized erythrocytes and in thrombocytopenia is also
      considered.

PMID- 8306507
TI  - IgG2 subclass restriction of anti-beta 2 glycoprotein 1 antibodies in autoimmune
      patients.
AB  - The IgG subclass and light chain distribution of antiphospholipid antibodies
      (aPL) occurring in autoimmune patients were determined by means of two
      radioimmunoassays using either cardiolipin- or beta 2 glycoprotein 1 (beta 2GP1)
      coated microtitre plates and mouse MoAbs. Of 50 sera selected for positivity of
      anticardiolipin antibodies (ACA) of the IgG isotype, 32 (64%) possessed anti-beta
      2GP1 antibodies and their presence was closely associated with clinical features
      of the antiphospholipid syndrome. Good correlations were found between ACA and
      anti-beta 2GP1 antibodies when considering antibody level and patterns of light
      chain and IgG subclass, suggesting that, overall, the same antibodies were being
      measured. Light chain analysis showed the polyclonal origin of these antibodies
      and, in most sera, a trend towards use of lambda chain. Among sera positive for
      anti-beta 2GP1 antibodies, IgG2 was the major subclass reactive with beta 2GP1
      and cardiolipin (87% and 74% of the IgG antibody activity, respectively). In
      contrast, in the group of 18 sera lacking anti-beta 2GP1 antibodies, ACA were
      largely restricted to IgG3, with a lesser contribution by IgG1. A few selected
      sera from the anti-beta 2GP1-positive group were shown to contain mixtures of
      antibodies that required beta 2GP1 (restricted to IgG2 present in large amounts)
      and did not require this cofactor (restricted to IgG3 and/or IgG1 present in low
      amounts) for their reactivity with cardiolipin. There was no contribution of
      glycosylation to the epitopes recognized by anti-beta 2GP1 antibodies, even
      though human anti-carbohydrate antibodies are restricted to the IgG2 subclass.
      These findings further emphasize the intra- and interindividual heterogeneity of
      aPL, and should help to discriminate clinically relevant specificies.

PMID- 8306508
TI  - Occurrence of C3 nephritic factor and C4 nephritic factor in
      membranoproliferative glomerulonephritis (MPGN).
AB  - One hundred patients diagnosed with hypocomplementaemic MPGN (C3 < 40%) were
      studied to determine the presence of C3 nephritic factor (C3NeF) and/or C4
      nephritic factor (C4NeF). Of those studied, 12 were C3NeF-positive, nine were
      C4NeF-positive and 10 were positive for both C3NeF and C4NeF. In the 10 patients
      both C3NeF- and C4NeF-positive, a marked decrease in C3 and C5 levels and a
      decrease in levels of late components from C6 to C9 were observed. This
      observation was in contrast to that seen in patients who were either C3NeF- or
      C4NeF-positive. Patients positive for both C3NeF and C4NeF continued to exhibit
      hypocomplementaemia after therapy. Immunofluorescent findings revealed heavy C3
      immunoglobulin deposits in the 10 patients who were both C3NeF- and C4NeF
      positive, whereas no such deposits were found in those patients who were either
      C3NeF- or C4NeF-positive only. When those patients who were both C3NeF- and C4NeF
      positive were compared with those who were either C3NeF- or C4NeF-positive,
      nephritic syndrome and a poor prognosis were observed more frequently. This study
      demonstrates a correlation between clinical outcome and hypocomplementaemic MPGN.
      Further investigations of MPGN as an autoimmune disease are necessary.

PMID- 8306509
TI  - IL-4 production is increased in cigarette smokers.
AB  - Cigarette smoking has been associated with both increases in serum levels of
      total IgE and an increased risk of developing allergic-like symptoms. IL-4 and
      interferon-gamma (IFN-gamma) have reciprocal roles in the regulation of IgE
      synthesis, and as such prompted us to evaluate, in smokers, the production of
      these two cytokines. We demonstrate that phytohaemagglutinin (PHA)-induced IL-4
      production by peripheral blood mononuclear cells (PBMC) of smokers (n = 19) is
      significantly higher than that of non-smokers (n = 10, P < 0.005). In addition,
      PBMC from heavy smokers, defined by the number of cigarettes smoked per day,
      produced significantly higher levels of IL-4 than those of light smokers. No
      difference between the groups was found for IFN-gamma production. Our data
      suggest an imbalance in cytokine production occurring in individuals who smoke.
      This imbalance, favouring IL-4 production, may be part of the mechanism
      responsible for the observed increases in serum IgE and allergic-like symptoms
      associated with cigarette smoking.

PMID- 8306510
TI  - Immunological effects of insulin-like growth factor-I--enhancement of
      immunoglobulin synthesis.
AB  - In addition to its activity as a metabolic hormone and a regulator of somatic
      growth, insulin-like growth factor-I (IGF-I) has cytokine-like activities on
      lymphoid cells. A 14-day infusion of recombinant human (rh)IGF-I increased
      lymphocyte numbers in all the peripheral lymphoid organs examined. This increase
      was apparent for up to 3 weeks following cessation of hormone treatment. A second
      administration of rhIGF-I, given when the lymphocyte numbers in the rhIGF-I
      treated mice had returned to control values, resulted in similar increases in the
      peripheral T and B cell populations. This increase in lymphocyte numbers had
      functional significance, since rhIGF-I-treated mice produced elevated antibody
      titres following primary or secondary antigen challenge compared with controls.
      In addition, when rhIGF-I-treated mice were immunized with a suboptimal dose of
      antigen they produced antibody titres which were equivalent to those generated by
      immunization with optimal doses of antigen. When examined in vitro, addition of
      rhIGF-I alone to cultures of splenocytes from antigen-primed mice stimulated
      immunoglobulin synthesis. These studies suggest that IGF-I produced locally by
      thymic and bone marrow stromal cells may be a natural component of B and T cell
      lymphopoiesis.

PMID- 8306511
TI  - Mature helper T cell requirement for immunoglobulin production by neonatal native
      B cells injected intraperitoneally into severe combined immunodeficient (SCID)
      mice.
AB  - It is accepted that human neonatal naive B cells produce mainly IgM in vivo as
      well as in vitro. Our previous work has demonstrated that i.p. injection of
      neonatal B cells together with adult mature T cells induces substantial levels of
      human IgG in the serum of SCID recipient mice. The present study was further
      attempted to determine the cellular components required for immunoglobulin
      production by neonatal B cells in SCID mice. When neonatal B and adult T cells
      were transferred into the SCID mice, human immunoglobulins, largely of IgG, were
      maximally detected in the serum around 6 weeks after a cell transfer. Depletion
      of CD4+ T cells from adult T cells resulted in undetectable levels of human
      immunoglobulin in the serum. By contrast, CD4+ T cell-enriched populations
      exhibited an enhancing effect on immunoglobulin production by neonatal B cells.
      Higher levels of immunoglobulin, including IgA and IgM, were detected in the
      peritoneal fluid than in the serum as early as 2 weeks after the cell transfer.
      Human T cells expressing activation antigens such as CD45RO and HLA-DR antigens
      were identified in the peritoneal lavages. These results suggest that neonatal
      naive B cells are able to differentiate into cells producing all classes of
      immunoglobulin in the presence of mature CD4+ T cells in a SCID mouse
      environment. The peritoneal cavity of SCID mice appears to provide a suitable
      place for immune responses by human cells, possibly in association with a certain
      xenogeneic reaction.

PMID- 8306512
TI  - Preventive effect of a new calcium antagonist, monatepil, on drug-induced
      ischaemic electrocardiographic changes in rats.
AB  - 1. The preventive effects of monatepil, a new calcium antagonist with alpha 1
      adrenoceptor blocking activity, on ischaemic electrocardiographic changes in rat
      models of vasospastic angina were evaluated and compared with those of the
      existing calcium antagonists (diltiazem, verapamil, nicardipine and nifedipine).
      2. In order to assess the contribution of the alpha 1-adrenoceptor blocking
      action of monatepil to its anti-vasospastic action, the anti-ST depression effect
      of prazosin, an alpha 1-adrenoceptor blocker, was also examined. 3. Monatepil
      given orally (3-30 mg/kg) inhibited vasopressin (0.2 IU/kg, i.v.)-induced ST
      depression which is considered to indicate ischaemic electrocardiographic changes
      in a vasospastic angina. This effect of monatepil was more potent and long
      lasting than that of diltiazem, and was similar to that of verapamil and
      nicardipine. At a dose of 30 mg/kg, monatepil produced a significant inhibition,
      even at 7 h after administration. 4. Monatepil given intravenously (0.3 mg/kg)
      exerted a significant inhibitory effect on methacholine (16 micrograms/kg,
      intracoronary arterial administration; i.c.a.)-induced ST elevation which seems
      to be caused by coronary vasospasm. This effect was more potent or equipotent to
      those of the existing calcium antagonists. 5. These results indicate that
      monatepil produces the preventive effect on the drug-induced ischaemic
      electrocardiographic changes in rats and suggest that monatepil may have
      potential for the treatment of vasospastic angina.

PMID- 8306513
TI  - Blood pressure effects of thromboxane A2 blockade in spontaneously hypertensive
      rats.
AB  - 1. The effects of CGS 22652, a thromboxane (Tx) A2 synthase inhibitor and
      TxA2/prostaglandin (PG) H2 receptor antagonist, on blood pressure (BP) were
      studied in conscious freely moving spontaneously hypertensive rats (SHR). 2.
      Three groups of 13 male SHR were subcutaneously infused from 5 to 11 weeks of age
      via osmotic minipumps with CGS 22652 at doses of 5 (SHRa) or 10 (SHRb) mg/kg per
      24 h or with the vehicle only (SHRc). A fourth group (SHRd, n = 13) was orally
      treated from 3 to 11 weeks of age with CGS 22652 (30 mg/kg) given by gavage once
      a day. 3. CGS 22652 dose-dependently reduced the age-related increase in systolic
      BP. The pressor response to noradrenaline (200 ng/kg, i.v.) but not to
      angiotensin I or II was slightly (P < 0.05) diminished in 11 week old SHRb and
      SHRd compared to SHRc. Acute ganglionic blockade by trimethaphan (10 mg/kg,
      i.v.), as well as angiotensin converting enzyme inhibition by perindopril (2
      mg/kg, i.v.) decreased BP to a similar extent in the four groups. After combined
      blockade of vasopressin receptors and of the autonomic nervous system and the
      administration of a direct vasodilator (hydralazine, 3 mg/kg, i.v.), the residual
      mean BP was identical in the four groups of rats. 4. Chronic treatment with CGS
      22652 dose-dependent antagonized the TxA2/PGH2 receptors but did not modify the
      TxA2 synthesis. The urinary sodium excretion did not differ between groups. 5. In
      conclusion, at the doses used, CGS 22652 given either orally or subcutaneously
      exhibited only TxA2/PGH2 receptor blocking properties in SHR.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8306514
TI  - Crossover comparison between the depressor effects of low and high work-rate
      exercise in mild hypertension.
AB  - 1. The relationship between work-rate and the antihypertensive effect of exercise
      in hypertensives, and the mechanism of that effect, were investigated by a
      crossover clinical trial. 2. Ten mild hypertensives were randomly divided into
      two groups. One group performed low work-rate exercise (LWE) on a cycle ergometer
      for 10 weeks (blood lactate threshold; approximately 50% of maximum oxygen
      consumption [Vo2max]). After a 10 week interval without exercise training, these
      subjects were then switched to a high work-rate exercise (HWE) regimen (4 mmol/L
      of blood lactate; approximately 75% of Vo2max) for another 10 weeks. In the other
      group, the order of exercise training was reversed. Since two patients withdrew
      from the protocol during HWE periods, statistical analysis was performed on the
      data from the remaining eight patients. There were no order effects observed in
      any of the data from the two groups. 3. During both LWE and HWE, resting blood
      pressure (BP) fell significantly after the initiation of exercise therapy (P <
      0.05). Furthermore, the overall effects of 10 weeks of LWE and HWE on BP were not
      significantly different. 4. The work-rate at the lactate threshold, which
      reflects physical fitness, had increased significantly by 16 W (P < 0.01) after
      the LWE period and by 11 W (P < 0.01) after the HWE. 5. During the LWE period,
      changes in haemodynamic and humoral variables were not significant, except for a
      reduction in plasma norepinephrine at week 10 (P < 0.05). In the HWE period,
      changes in haemodynamic and humoral variables were not significant.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8306515
TI  - The marine natural product 3,5-dibromo-2-(2,4-dibromo-phenoxy)phenol, inhibits
      contractile activity in the guinea-pig ileum.
AB  - 1. The tetrabrominated diphenyl ether 3,5-dibromo-2-(2,4-dibromophenoxy)phenol
      (BPE), a natural marine product isolated from a sponge, was tested for
      pharmacological activity in guinea-pig ileum. 2. BPE (2 mumol/L) decreased basal
      force and the frequency of spontaneous contractions of the ileum. It also
      significantly decreased contractions of the ileum induced by 5 mmol/L barium and
      to electrical stimulation at parameters which stimulated intrinsic nerves. 3. The
      slopes of concentration-response curves to acetylcholine (ACh), histamine and 5
      hydroxytryptamine (5-HT) were significantly reduced by BPE at concentrations of 2
      mumol/L or greater. 4. BPE (2 mumol/L) did not affect calcium-induced
      contractions of longitudinal muscle fibres from guinea-pig ileum which were
      stripped of their cellular membrane. It (6 mumol/L) also had no effect on ATP
      levels in longitudinal muscle fibres. 5. BPE (2 mumol/L) reduced both phasic and
      tonic components of contractions induced by raising the extracellular
      concentration of K+ to 15, 30, 45 or 60 mmol/L (in the presence of atropine,
      propranolol, phentolamine and desensitization to 5-HT to inhibit the effects of
      nerve transmitter release). 6. BPE (2 mumol/L) reduced carbachol-induced
      contractions of ileum pre-incubated in 1 mumol/L felodipine, a blocker of L-type
      voltage-operated calcium channels (VOCC). 7. BPE dose dependently (0.6-6 mumol/L)
      reduced contractions induced by Ca2+ in both K+ depolarized ileum and in tissue
      exposed to carbachol (10 mumol/L) in the presence of felodipine (0.1 mumol/L). 8.
      These results suggest that BPE affects intracellular messenger systems
      controlling cytosolic calcium and/or blocks entry of calcium into the cell
      through both VOCC and receptor-operated channels (ROC).

PMID- 8306516
TI  - Methodological evaluation of indirect calorimetry data in lean and obese rats.
AB  - 1. The applicability of current indirect calorimetry formulae to the study of
      energy and substrate balances on obese rats has been evaluated. The energy
      consumption of series of 60-day rats of Wistar, lean and obese Zucker stock were
      studied by means of direct and indirect calorimetry, and by establishing their
      energy balance through measurement of food intake and retention. Calorimetric
      studies encompassed a 24 h period, with gas and heat output measurements every 2
      or 5 min, respectively, for direct and indirect calorimetry. 2. The analysis of
      fat composition (diet, whole rat, and synthesized and oxidized fat) showed only
      small variations that had only a limited effect on the overall energy equation
      parameters. 3. A gap in the nitrogen balance, which represents a urinary N
      excretion lower than the actual protein oxidized, resulted in significant
      deviations in the estimation of carbohydrate and lipid oxidized when using the
      equations currently available for indirect calorimetry. 4. Analysis of the amino
      acid composition of diet and rat protein as well as of the portion actually
      oxidized, and correcting for the nitrogen gap allowed the establishment of a set
      of equations that gave better coincidence of the calculated data with the
      measured substrate balance. 5. The measured heat output of all rats was lower
      than the estimated values calculated by means of either indirect calorimetry of
      direct energy balance measurement; the difference corresponded to the energy lost
      in water evaporation, and was in the range of one-fifth of total energy produced
      in the three rat stocks. 6. Wistar rats showed a biphasic circadian rhythm of
      substrate utilization, with alternate lipid synthesis/degradation that reversed
      that of carbohydrate, concordant with nocturnal feeding habits. Zucker rats did
      not show this rhythm; obese rats synthesized large amounts of fat during most of
      the light period, consuming fat at the end of the dark period, which suggests
      more diurnal feeding habits. Lean Zucker rats showed a similar, but less marked
      pattern. 7. The results obtained indicate that lean and obese rats can be studied
      using the same indirect calorimetry formulae provided that there is an adequate
      measure of protein oxidation and the composition of diet does not differ.

PMID- 8306517
TI  - Selectivity of calcium antagonist drugs on vascular smooth muscle.

PMID- 8306518
TI  - Respiratory alterations with intrapericardial procaine in the conscious rabbit.
AB  - 1. Intrapericardial procaine, used to produce cardiac nerve blockade in both
      conscious and anaesthetized animals, has been reported to also produce changes in
      respiration. This study systematically investigated the effects of two doses of
      intrapericardial procaine on respiration in the conscious rabbit. 2. Rabbits were
      pre-instrumented with a chronic diaphragm electromyogram (dEMG) recording
      electrode and intrapericardial catheter. Arterial pressure, heart rate, dEMG and
      respiratory excursions (recorded with a pneumograph) were monitored in the
      conscious rabbit before and after intrapericardial and intravenous infusion of 2
      and 5% procaine. Efficacy of cardiac nerve blockade was tested by intravenous
      infusion of phenyl biguanide. Arterial blood gases were determined at rest and
      during changes in respiration. 3. Following a low dose of intrapericardial
      procaine (12 mg), dEMG and respiratory excursions increased (65 +/- 13 and 76 +/-
      32%, respectively) with no change in breathing frequency or arterial blood gases.
      Following a high dose of intrapericardial procaine (30 mg), four of six animals
      exhibited a similar response. However, four of the six rabbits also exhibited a
      second type of response pattern characterized by a further increase in
      respiratory efforts (430 +/- 336%), abolition of dEMG, and a mild hypoxaemia. 4.
      Intravenous infusion of a low dose of procaine was without effect, whereas
      intravenous infusion of a high dose of procaine produced minor behavioural
      responses. 5. In four additional anaesthetized rabbits, it was demonstrated that
      high doses of intrapericardial procaine anaesthetized the phrenic nerve to
      produce the observed alterations in respiration. 6. We conclude that if
      intrapericardial procaine is used to block cardiac nerves in conscious rabbits,
      it should be used in a low concentration and at the lowest possible total dose to
      avoid complications due to changes in respiration.

PMID- 8306519
TI  - Effect of dietary sodium chloride on the development of renal glomerular and
      vascular lesions in hypertensive rats.
AB  - 1. The hypothesis that high levels of NaCl in the diet aggravates hypertension
      associated renal vascular lesions was examined in unilaterally nephrectomized
      deoxycorticosterone acetate treated (DOCA) and two kidney one clip (2K1C)
      hypertensive rats, as well as normotensive controls. 2. High NaCl diet
      significantly increased systolic blood pressure (SBP) in DOCA rats, but had
      little effect on SBP in normal control rats, and did not affect the rise of SBP
      in 2K1C rats. 3. High NaCl diet was associated with a higher percentage of
      glomerular lesions and renal arterial and arteriolar lesions in DOCA and 2K1C
      rats (P < 0.05). 4. Thus high NaCl intake exacerbated renal arterial and
      arteriolar and glomerular lesions in both DOCA and 2K1C hypertensive rats. In
      2K1C rats this effect may be in part independent of blood pressure.

PMID- 8306520
TI  - Endothelium-derived relaxing factor, hypertension and chronic parathyroidectomy
      in spontaneously hypertensive and Wistar-Kyoto rats.
AB  - 1. Parathyroidectomy (PTX) lessens the development of hypertension in young
      spontaneously hypertensive rats (SHR) and the involved mechanisms remain to be
      elucidated. We have studied here the aortic vascular reactivity to both
      norepinephrine (NE) and acetylcholine in 10 week old male PTX SHR and Wistar
      Kyoto (WKY) rats. 2. Depolarized (KCl 100 mmol/L) and NE (1 mumol/L or cumulative
      10(-9)-10(-5) mol/L) precontracted intact aortic rings from PTX rats show a
      significant and unexpected increase of maximal contractile responses in
      normotensive and hypertensive animals. These results are also obtained with low
      extracellular ionized calcium levels (0.625 and 0.9 mmol/L) similar to PTX
      ionized plasma calcium. N omega-Nitro-L-arginine methyl ester (L-NAME, 20
      mumol/L) potentiates the NE response in SHR and WKY rats, more significantly in
      control than in PTX animals. 3. In the presence of indomethacin (10 mumol/L) in
      SHR the potentiating effect of PTX on NE contraction is still observed, ruling
      out a specific production of vasoconstrictors from the arachidonic cascade by the
      PTX rat aortic endothelium. 4. After PTX a moderate impairment of acetylcholine
      relaxant responses is observed in SHR and WKY rat aortas and basal aortic cyclic
      guanosine 3'-5' monophosphate (cGMP) content is also decreased; nevertheless
      sodium nitroprusside causes a similar relaxation. Furthermore in L-NAME-treated
      aortas and in the presence of L-arginine (100 mumol/L), acetylcholine (1 mumol/L)
      produces a significantly less pronounced relaxation in PTX rats. 5. In
      conclusion, the enhancement of NE contractile response in PTX rat aortas is not
      linked to the strain but probably related to a decrease in endothelial nitric
      oxide (NO) release or activity. Enhancement of force generation that we describe
      does not directly participate in the attenuated hypertension observed in SHR
      after parathyroidectomy.

PMID- 8306521
TI  - Summary of 1993 WHO/ISH guidelines for the management of mild hypertension:
      memorandum from a WHO/ISH meeting. Guidelines Sub-Committee of WHO/ISH Mild
      Hypertension Liaison Committee.

PMID- 8306522
TI  - AII receptor number and screening for PIH.

PMID- 8306523
TI  - The loss of E-cadherin mRNA transcripts in rat prostatic tumors is accompanied by
      increased expression of mRNA transcripts encoding fibronectin and its receptor.
AB  - We compared the levels of mRNA transcripts encoding E-cadherin, N-cadherin, beta
      1 integrin subunit, alpha 5 integrin subunit and fibronectin in the normal rat
      prostate gland, as well as in tumors derived from three invasive sublines (G,
      MatLyLu, AT-2) of the Dunning R-3227 rat prostatic adenocarcinoma. E-cadherin
      mRNA transcripts were only detectable in total RNA extracts prepared from normal
      rat prostates, whereas N-cadherin mRNA transcripts were only found in normal rat
      brains. In contrast, the mRNA transcripts encoding the beta 1 integrin subunit,
      alpha 5 integrin subunit and fibronectin were all elevated in the tumors, as
      compared to the levels of these transcripts in normal tissues. Our results
      suggest that there is an inverse correlation between cadherin and integrin mRNA
      levels in rat prostatic tumors.

PMID- 8306524
TI  - Desialylation of metastatic human colorectal carcinoma cells facilitates binding
      to Kupffer cells.
AB  - Cell surface hypersialylation of human colorectal carcinoma (HCRC) cells
      correlates with increased metastatic potential after intrasplenic injection,
      while desialylation with various agents has been shown to inhibit hepatic
      metastases. In this study we examined the effects of desialylation of HCRC cell
      lines with a novel intracellular inhibitor of the CMP-sialic acid transport
      protein (KI-8110). HCRC cells, which are poorly differentiated and poorly
      metastatic in nude mice (Clone A and MIP-101) were compared to well
      differentiated, highly metastatic cells (CX-1 and CCL-235). KI-8110 treatment has
      previously been shown to reduce sialic acid levels in each of these cell lines
      and to reduce hepatic metastases in CX-1 and CCL-235 cell lines. This study
      attempts to identify a mechanism by which desialylation inhibits hepatic
      metastases. After KI-8110 treatment, in vitro adhesion assays were performed with
      each cell line to examine binding to Kupffer cells and the extracellular matrix
      protein fibronectin. Binding of Clone A, CX-1, and CCL-235 to Kupffer cells was
      significantly increased after KI-8110 treatment. Desialylation had no significant
      effect on binding of HCRC cell lines to fibronectin. While the metastatic cascade
      involves many complex interactions, the cytotoxic effects of Kupffer cells in the
      hepatic sinusoid are known to be an important mechanism of host defense against
      tumor cells. Cell surface sialic acids may well mask Kupffer cell binding to HCRC
      cells, preventing their cytotoxic effects and enhancing the metastatic potential
      of circulating tumor cells.

PMID- 8306525
TI  - Urinary trypsin inhibitor (UTI) and fragments derived from UTI by limited
      proteolysis efficiently inhibit tumor cell invasion.
AB  - We investigated the effects of purified human urinary trypsin inhibitor (UTI) and
      fragments derived from UTI by proteolysis on the invasive potential of ovarian
      cancer cells (HOC-I) and gestational choriocarcinoma cells (SMT-ccl) using an in
      vitro reconstituted basement membrane invasion assay. These cells express cell
      associated plasmin and functional uPA receptors that are partially occupied by
      ligands. SMT-ccl cells, which express threefold higher levels of cell-associated
      plasmin activity than HOC-I cells, showed approximately twofold increase in their
      invasive potential. For the invasion assay, HOC-I cells were primed with
      exogenous plasminogen, but SMT-ccl cells were not. Human leukocyte elastase (HLE)
      digested UTI (22 kDa fragment; UTI-22) inhibited plasmin practically with the
      same strength as native UTI. Trypsin-digested UTI (20 kDa fragment; UTI-20),
      however, did not inhibit plasmin significantly. Treatment of cells with UTI or
      UTI-22 reduced the incidence of tumor cell invasive capacity, whereas the
      inhibitory effect of UTI-20 was not remarkable. The inhibitory effect on tumor
      cell invasion was dose-dependent and non-toxic; moreover, it was not mediated by
      inhibition of the tumor cell chemotactic response or of cell attachment to
      matrigel. These results indicate that inhibition of the proteolytic enzyme
      plasmin specifically reduced the invasive capacity of tumor cells in vitro.

PMID- 8306526
TI  - Expression of Lewis(x) sugar structure in the liver metastasis of mouse colon
      carcinoma (colon 26) cells.
AB  - Immunohistochemical aspects of the process of experimentally induced metastasis
      were examined by light and electron microscopy employing a series of labeled
      carbohydrate-specific monoclonal antibodies as probes. Liver metastasis was
      induced by injecting mouse colon carcinoma cell (colon 26) into the spleen of
      Balb/c mice. Labeled anti-Lewis(x) (Le(x)) antibody stained the metastasized
      colon 26 cells strongly compared with the heterogeneous and faint staining in non
      metastasized tumor foci in the spleen or in the subcutaneous space. Other
      antibodies having specificities for Lewis-related antigens other than Le(x), e.g.
      those against Le(y), Le(a), Le(b), sialyl Le(x) and sialyl Le(a), did not show
      any differences in binding between metastasized cells and non-metastasized tumor
      foci. Immunoelectron microscopy revealed the expression of Le(x)-carbohydrate in
      the plasma membranes as well as in the intercellular spaces of metastasized colon
      26 cells in the liver. Based on these results, it is likely that sugar chains
      containing the Le(x)-carbohydrate structure are involved in the interactions
      between colon 26 cells and hepatic cells during the process of liver metastasis.

PMID- 8306527
TI  - Antimetabolite-induced increases in the invasive capacity of murine leukaemia
      L1210 cells.
AB  - Pretreatment of murine leukaemia L1210 cells with non-lethal concentrations of
      various antimetabolites increased the in vitro invasive capacity of these cells
      into monolayers of rat embryo fibroblasts. The increase in invasive capacity was
      partly correlated with the induced cell cycle arrest. The concomitant increase in
      cell surface fucosylation and inhibition of invasion with sulphate indicate a
      role for glycoproteins in this process. Our results suggest that treatment with
      antimetabolites may lead to a more aggressive phenotype by altering cell surface
      properties.

PMID- 8306528
TI  - Hepatocyte growth factor stimulates invasion across reconstituted basement
      membranes by a new human small intestinal cell line.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a protein growth factor whose
      pleiotropic effects on epithelial cells include the stimulation of motility,
      mitosis and tubulogenesis. These responses are mediated by the cell surface
      tyrosine kinase receptor c-met. Because both the cytokine and receptor are found
      in the gastrointestinal tract, we have studied the effects of HGF/SF on
      transformed gut epithelial cells which express c-met. Here we describe the
      response of a new transformed human jejunal epithelioid cell line (HIE-7) to
      HGF/SF. Morphologically HIE-7 cells are immature. Their epithelial lineage was
      confirmed by reactivity with the epithelial specific antibodies AE1/AE3, Cam 5.2,
      Ber-EP4 and anti-EMA and is consistent with their expression of c-met mRNA and
      protein. In addition, electron microscopic analysis revealed the presence of
      primitive junctions and rudimentary microvilli, but features of polarization were
      absent. When grown on reconstituted basement membranes, HIE-7 cells formed
      closely associated multicellular cord-like structures adjacent to acellular
      spaces. However, the cells did not mature structurally, form lumen-like
      structures or express disaccharidase mRNA, even in the presence of recombinant
      HGF (rHGF). On the other hand, rHGF induced HIE-7 cells to scatter and stimulated
      their rapid migration in a modified wound assay. To determine whether the
      mitogenic effect caused by rHGF is associated with HIE-7 cell invasiveness across
      reconstituted basement membranes, a Boyden chamber chemoinvasion assay was
      performed. rHGF stimulated a 10-fold increase in the number of HIE-7 cells that
      crossed the basement membrane barrier, while only stimulating a small increase in
      chemotaxis across a collagen IV matrix, suggesting that the cytokine activates
      matrix penetration by these cells. rHGF also stimulated the invasion of basement
      membranes by an undifferentiated rat intestinal cell line (IEC-6) and by two
      human colon cancer cell lines which are poorly differentiated (DLD-1 and SW 948).
      In contrast, two moderately well differentiated colon cancer cell lines (Caco-2
      and HT-29) did not manifest an invasive response when exposed to rHGF. These
      results suggest that HGF/SF may play a significant role in the invasive behavior
      of anaplastic and poorly differentiated gut epithelial tumors.

PMID- 8306529
TI  - Differential purification of autocrine motility factor derived from a murine
      protein-free fibrosarcoma.
AB  - We have previously shown that a protein-independent growing fibrosarcoma, Gc-4 PF
      has a high motile response to its cultured medium, which is associated with an
      increase in expression of gp78, a cell surface receptor for autocrine motility
      factor (AMF). Here we show that the cultured medium contains two motile
      activities, acidic and basic AMFs with regard to binding features on ion exchange
      chromatography. These two AMFs were purified by sequential DEAE anion exchange,
      CM cation exchange, and gel filtration chromatographies. However, both acidic and
      basic AMFs have a similar size of 55 kDa and 65 kDa under non-reducing and
      reducing conditions, respectively, with the same pI of 6.5. The stimulated
      motility of both AMFs was inhibited by the pertussis toxin (PT), but not by
      Streptomyces hyaluronidase. These two AMFs significantly stimulated the lung
      colonizing properties of the self-producing cells by 1.5-fold. These results
      suggest that both acidic and basic AMFs may correspond to the previously reported
      AMF and confirm directly that the AMF-gp78 signaling pathway is involved in cell
      motility associated with metastatic property.

PMID- 8306530
TI  - The role of the spleen in the organ-specific metastasis of murine BW 5147 T
      lymphomas.
AB  - Organ-specific metastasis of tumour cells may result from selective invasion and
      growth or from selective host cell responses. The present study demonstrates how
      selective interactions with the host affect the metastatic pattern of two murine
      T cell hybridoma lines, derived from the BW 5147 thymoma. Upon intravenous
      inoculation into syngeneic mice BW-14 cells preferentially colonize the kidneys,
      whereas BW-19 cells metastasize mainly to the spleen and the liver. The organ
      specific behaviour of the two cell lines appears to be determined by a
      differential interaction with the spleen microenvironment. Inoculation of BW-14
      cells into splenectomized mice results in increased liver colonization,
      indicating a negative effect of the spleen on BW-14 tumour development in the
      liver. Macrophages are likely to be involved in this inhibition, since
      inoculation of BW-14 cells into macrophage-depleted mice also leads to increased
      liver and spleen metastasis. In contrast, inoculation of BW-19 cells into
      splenectomized mice results in decreased liver metastasis, which indicates that
      the spleen exerts a stimulating effect on BW-19 cells. Macrophages also appear to
      be involved in this stimulation, since macrophage depletion causes a similar
      decrease in liver and spleen colonization. Hence components of the splenic
      microenvironment, probably macrophages, exert inhibiting or stimulating
      activities on BW-14 or BW-19 cells respectively, thereby determining the
      subsequent liver or kidney colonization.

PMID- 8306531
TI  - Luciferase activity as a marker of tumor burden and as an indicator of tumor
      response to antineoplastic therapy in vivo.
AB  - The gene encoding firefly luciferase has been used as a reporter gene for the
      study of gene function. The luciferase catalyzes its substrate and subsequently
      produces luminescence. In addition, it is not present in mammalian cells. We have
      therefore explored its use in monitoring the growth of tumors in vivo. The
      luciferase gene was transfected into two murine tumor lines, i.e. c162 melanoma
      and M109 lung carcinoma, and the luciferase activity associated with the cells
      was determined by a rapid chemiluminescent reaction. Luciferase activity was well
      correlated with the number of tumor cells in vitro. Luciferase activity also
      correlated with the tumor burden in vivo, as well as with the effect of an
      adoptive T cell transfer therapy in the syngeneic C3H/HeN mice experimental tumor
      model. This assay offers the advantage of being quantitative, rapid, and reliable
      for the detection of tumor burden and for the evaluation of the effect of
      antineoplastic therapy.

PMID- 8306532
TI  - Antimetastatic action and toxicity on healthy tissues of Na[trans-RuCl4(DMSO)Im]
      in the mouse.
AB  - The ruthenium-dimethylsulfoxide complex Na(trans-RuCl4(DMSO)Im] was given i.v. to
      mice bearing MCa mammary carcinoma and its effects on tumor growth and on healthy
      host tissues were studied by macroscopic examination of primary tumor growth, by
      survival time, and by histological analysis using light microscopy and SEM.
      Either by means of vivo-vivo bioassays or by microscopic examination it appeared
      that the growth of lung tumors was markedly reduced, whereas the growth of the
      i.m. primary tumor was much less affected. These effects account for the
      prolongation of survival time and for the cure rate observed. The favourable
      effect on survival time was also influenced by the lack of significant
      cytotoxicity for normal tissues such as lung and kidney epithelia, muscle and
      liver cells, splenocytes and bone marrow. It thus appears that the selective
      interaction with tumor cells in the lungs cannot simply be attributed to a
      selectively higher localization of the compound at this site, nor to a
      modification of the histological structure of primary tumor. These results
      highlight the pharmacologic properties of this compound for the control of solid
      tumor metastases, an effect that was shown to be similarly exerted on advanced
      tumor metastases.

PMID- 8306533
TI  - Errors in death certificate completion in a teaching hospital.
AB  - A retrospective chart review was conducted to determine the types and frequency
      of errors, other than those of diagnostic accuracy, made in recording information
      on death certificates and to assess factors that might affect those rates. The
      sample (n = 426) consisted of 50% of all deaths in a London, Ontario teaching
      hospital over one year. For each certificate reviewed, 6 questions were asked
      based on W.H.O. guidelines: 1) Was there an acceptable cause of death? 2) If
      mechanisms of death were recorded, were they adequately explained by an
      underlying cause of death? 3) Were there any sequencing errors? 4) Were there 2
      competing causes of death listed? 5) Was there recorded any time interval between
      onset of the condition and death? 6) Was there any other inappropriate
      information recorded? The death certificates were filled out in an acceptable
      fashion 68.1% of the time. Comparing the 6 major departments in the hospital,
      there was significant difference in the error rates of the different departments
      (p = .0035). Error rates were not significantly better for certificates that had
      been signed by a coroner nor in those that had an autopsy performed. The majority
      of the death certificates (89.4%) were completed by house staff. More attention
      has to be devoted to raising physicians' awareness of the types of errors made in
      completing death certificates. Recurring educational sessions and feedback, if
      provided in teaching hospitals, could be helpful to increase the accuracy of
      these important documents.

PMID- 8306535
TI  - A method to evaluate renal ammoniagenesis in vivo.
AB  - A reduced rate of excretion of ammonium (NH4+) can be due to either a low rate of
      production and/or a low transfer of NH4+ to the urine. At present, there is no
      way to obtain a measure of the rate of production of NH4+ in vivo without
      invasive techniques. Hence, our purpose was to develop a non-invasive test to
      reflect this rate in vivo. Conditions were selected so that there would be a wide
      range in the rate of production of NH4+ in the kidney. Initial experiments were
      performed in dogs because both the rate of production and excretion of NH4+ could
      be measured directly. The rate of excretion of NH4+ in normal dogs on their usual
      diet varied over a wide range and was not directly related to its rate of
      production. Nevertheless, 59% of the NH4+ produced was excreted when the pH of
      urine was < 6 or when the rate of flow of urine was high (after administering a
      loop diuretic). To produce a urine with a low pH and high flow rate in humans, a
      loop diuretic (20 mg of furosemide) and a mineralocorticoid (200 micrograms of
      fludrocortisone) were given. The pH of urine fell to 5.1 and the rate of urine
      flow rose to 8 ml/min; the rate of excretion of NH4+ rose from 21 to 33 mumol/min
      when the urine flow rate rose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306534
TI  - In vitro effects of cytokines and human thyroglobulin on the induction of
      antibody-secreting cells in patients with auto-immune thyroid disease.
AB  - We have investigated the in vitro effects of interleukin-1-beta (IL-1-beta),
      interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), and interferon
      gamma (IFN-gamma) on the induction of anti-thyroperoxidase (anti-TPO), anti
      thyroglobulin (anti-Tg), and IgG-secreting cells (SC) by cultures of pokeweed
      mitogen (PWM)-stimulated peripheral blood mononuclear cells (PBMC) obtained from
      patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), and controls
      (C). The effect of human thyroglobulin (Tg) together with cytokines was also
      studied. No differences in the numbers of PWM-induced IgG-SC were found. However,
      greater numbers of PWM-induced anti-TPO-SC were observed in the HT preparations
      compared to C, either with or without the addition of Tg (p < 0.05). Inhibition
      of numbers of IgG-SC with certain cytokines in all 3 groups of preparations was
      observed (0.01 < p < 0.05). Decreased numbers of anti-TPO-SC were noted in HT
      preparations after exposing cells to IL-2 and TNF-alpha. Induction of anti-TPO-SC
      after addition of Tg plus cytokines was significantly lower in HT than in the
      other 2 groups. In contrast, induction of anti-TPO-SC in C was markedly increased
      by all cytokines, which was enhanced by Tg. These data suggest that cytokines
      play a role in auto-antibody regulation in auto-immune thyroid disease (AITD).

PMID- 8306536
TI  - Flow limitation while breathing HeO2.
AB  - Flow limitation during a maximum expiratory flow-volume curve (MEFVC) while
      breathing air occurs at lung volumes below 70% vital capacity (VC). To evaluate
      small airways function, use has been made of the volume of isoflow (VisoV),
      comparing an MEFVC done in air to one done in 80% helium, 20% O2 (HeO2). The
      VisoV has high intra-subject variability. This study investigated whether this
      variability was due to an inability to flow limit while breathing HeO2. This
      would occur if the velocity of expiratory muscle contraction did not result in
      sufficient intrathoracic pressures to cause dynamic airway compression in the
      face of increased expiratory flows while breathing HeO2. Seven healthy adult male
      subjects performed repeated VC expirations of varying effort with an esophageal
      balloon in place in a body plethysmograph while breathing air and HeO2. The flow
      volume curves were matched at residual volume and transpulmonary pressure-flow
      plots were constructed at volume isopleths of 70, 50, and 25% VC. In air, flow
      limitation was demonstrated in 3, 6, and 7 subjects at 70, 50, and 25% VC,
      respectively. In HeO2, flow limitation was achieved in 1 and 4 subjects at 70 and
      50% VC. Although one subject demonstrated intermittent glottic closure, the
      remaining 6 demonstrated flow limitation at 25% VC. We concluded that dynamic
      airways compression occurs even with the increased flows in HeO2.

PMID- 8306538
TI  - Chemotherapy of malaria: a battle against all odds?
AB  - The most important treatment of malaria to date is chemotherapy using a number of
      different natural and synthetic drugs. Antifolates, such as pyrimethamine,
      inhibit the parasite's dihydrofolatereductase, whereas the aminoquinolines, such
      as chloroquine, have the digestive vacuole as their major site of action. The use
      of these drugs in chemotherapy of malaria infections is strongly hampered by
      widespread resistance and in this review current knowledge on the molecular
      mechanisms of resistance is discussed. Finally, new antimalarial drugs and
      treatment strategies are considered which may offer new possibilities for the
      treatment of malaria resistant to the drugs currently in use.

PMID- 8306537
TI  - Absence of an effect of ferrous sulfate on phenytoin absorption in the rat.
AB  - A variety of drugs which bind to iron have significant reductions in absorption
      when co-administered with iron compounds. The chemical structure of phenytoin
      indicates that there may be possible binding to iron ions. In vitro experiments
      were performed to determine whether any binding of iron to phenytoin occurred,
      and in vivo studies examined the effect of ferrous sulfate on phenytoin
      absorption in an isolated perfused rat jejunal model of drug absorption. The dose
      of phenytoin was limited by solubility and represents a human dose of 28 mg on a
      mg/kg basis for the rat assuming the total dose to be in 10 cm bowel in the rat.
      The ferrous sulfate doses were chosen to represent 28 and 300 mg doses on a
      similar basis to phenytoin. There was no significant effect of ferrous sulfate on
      phenytoin absorption or instability of phenytoin in the presence of ferrous
      sulfate in the rat. In vitro experiments indicated that little or no phenytoin
      binding to iron occurred. Results from animal model studies using low doses of
      phenytoin suggest it is unlikely that there will be a significant reduction in
      phenytoin absorption during concurrent therapy with iron salts.

PMID- 8306539
TI  - Metabolic aspects of metabolic acidosis.

PMID- 8306540
TI  - Canadian Bacterial Diseases Network: a new approach to university-industry
      relationships.
AB  - Bacterial diseases are a substantial problem worldwide. Their diagnosis and
      therapy form the basis of a multibillion dollar industry. This industry is
      dynamic and is continuously revitalized by research. The Canadian Bacterial
      Diseases Network (CBDN) was established to capitalize on the enhanced
      opportunities that now exist for the rapid progression of an idea from
      conceptualization to implementation and, ultimately, commercialization. CBDN is
      one of 15 Networks of Centres of Excellence, a Federal Government initiative
      whose intention is to improve Canada's economic competitiveness in the global
      market. CBDN research involves fundamental science, is broadly-based, and
      encompasses all aspects of bacterial diseases. Current projects include the
      investigations of strategies to block Pseudomonas aeruginosa binding to
      epithelial cells and a novel anti-toxin approach for Escherichia coli. Also CBDN
      is investigating the basis for antibiotic resistance in Gram-negative bacteria,
      and is devising improved procedures for overcoming such resistance mechanisms.
      CBDN is only 28 months into its first 4-year mandate; however, considerable
      successes have been enjoyed to date.

PMID- 8306541
TI  - Hereditary breast-ovarian cancer: how can we use the new DNA markers to improve
      patient management?

PMID- 8306542
TI  - 95th Annual Meeting of the American Society for Clinical Pharmacology and
      Therapeutics. New Orleans, Louisiana, March 30-April 1, 1994. Abstracts.

PMID- 8306543
TI  - Hormonal and other mechanisms involved in the pathogenesis of cyclosporin-induced
      nephrotoxicity and hypertension in man.

PMID- 8306545
TI  - Erythrocyte ion transport alterations in hypertriglyceridaemic rats.
AB  - 1. Hypertension appears to be associated with both abnormalities in ion transport
      and disturbances in lipid metabolism. The aim of the present study was to search
      for alterations in erythrocyte ion transport in hereditary hypertriglyceridaemic
      rats. This strain is characterized by a pronounced elevation of blood pressure
      which correlates with the plasma triacylglycerol level. 2. Erythrocyte Na+
      content was elevated in hypertriglyceridaemic rats due to an increased ouabain
      resistant Na+ net uptake. This was caused not only by the acceleration of
      bumetanide-sensitive Na+ inward co-transport, but also by the augmentation of
      bumetanide-resistant Na+ inward leak. A moderate enhancement of bumetanide
      sensitive Rb+ uptake was seen in hypertriglyceridaemic animals, but there were no
      changes in bumetanide-resistant Rb+ leak. 3. The plasma triacylglycerol level
      correlated positively not only with blood pressure (P < 0.001) but also with
      ouabain-resistant Na+ transport (P < 0.002), bumetanide-sensitive Na+ and K+
      (Rb+) co-transport (P < 0.01 and P < 0.001, respectively), bumetanide-resistant
      Na+ leak (P < 0.02) and erythrocyte Na+ content (P < 0.05). 3. Thus the
      association of augmented ouabain-resistant Na+ transport with elevated blood
      pressure in this form of experimental hypertension might be mediated by genetic
      disorders of lipid metabolism.

PMID- 8306544
TI  - Nitrogen homeostasis in man: the diurnal responses of protein synthesis and
      degradation and amino acid oxidation to diets with increasing protein intakes.
AB  - 1. The diurnal changes in whole body protein turnover associated with the
      increasing fasting body nitrogen (N) losses and feeding gains with increasing
      protein intake were investigated in normal adults. [13C]Leucine,
      [2H5]phenylalanine and [2H2]tyrosine kinetics were measured during an 8 h primed,
      continuous infusion during the fasting and feeding phase together with fed-state
      N turnover assessed with [15N]glycine after 12 days of adaptation to diets
      containing 0.36 (LP), 0.77 (MP), 1.59 (GP) and 2.07 (HP) g of protein day-1 kg-1.
      Measurements were also made of fasting and fed resting metabolic rate and plasma
      hormone levels. 2. Resting metabolic rate in the fasted and fed state was not
      influenced by dietary protein intake, but was increased by feeding (11-13%, P <
      0.01) with no influence of dietary protein concentration. Fasting plasma insulin
      levels were not influenced by protein intake and were increased by feeding
      independent of protein intake. Fasted but not fed values of insulin-like growth
      factor-1 increased with protein intake, although no feeding response was
      observed. Thyroid hormones (free and total tri-iodothyronine) did not change in
      any state. 3. For leucine with increasing protein intake the increasing fasting
      losses reflected increasing rates of protein degradation, although the changes
      were small and only significant between GP and MP intakes. The increasing leucine
      gain on feeding was associated with increasing rates of protein synthesis and
      falling rates of protein degradation, reflecting a progressive inhibition of
      degradation with feeding, and a change from inhibition of synthesis (LP diet) to
      stimulation (GP and HP diets). Mean daily rates of synthesis and degradation did
      not change with protein intake. 4. Phenylalanine and tyrosine kinetics were
      calculated from adjusted values based on leucine kinetics and published data of
      the hepatic/plasma enrichment ratio. With the increased protein intake, the
      increasing fasting losses of phenylalanine (GP > MP) were mediated by increasing
      rates of degradation (paired t-tests). The increasing phenylalanine gain (GP > MP
      > LP) was due to increasing fed-state rates of synthesis and falling rates of
      degradation, reflecting a progressive inhibition of degradation, a stimulation of
      hydroxylation and a variable response of synthesis ranging from inhibition at the
      lowest intake to stimulation at higher intakes. For tyrosine a similar
      progressive inhibition of degradation with intake was shown. Mean daily rates of
      synthesis and degradation (phenylalanine) and degradation (tyrosine) did not
      change with protein intake.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8306546
TI  - Appendix: protein turnover measurement by the leucine oxidation-nitrogen
      excretion end-product method.

PMID- 8306547
TI  - Muscle blood flow during intermittent exercise: comparison of the microdialysis
      ethanol technique and 133Xe clearance.
AB  - 1. Local skeletal muscle blood flow was monitored using the microdialysis ethanol
      technique and 133Xe clearance during intermittent isometric contractions (5 s
      on/10 s off) of the thigh at 0-60% of the maximal voluntary isometric contraction
      force. 2. A linear increase in blood flow over a 25-fold range was detected using
      both 133Xe clearance and the microdialysis ethanol technique. 3. The median
      correlation coefficient between percentage maximal voluntary isometric
      contraction force and the ethanol outflow/inflow ratio, a marker of blood flow,
      was r = -0.98 (-0.94 to -0.99) (median and range, n = 6). The corresponding
      correlation coefficient for 133Xe clearance was r = 0.97 (0.92-0.98), the
      correlation coefficient between the ethanol outflow/inflow ratio and 133Xe
      clearance being r = -0.92 (-0.89 to -0.94). 4. Dialysate glucose concentration,
      although affected by blood flow, was not always significantly correlated with
      blood flow changes (r = 0.70; 0.51-0.95). 5. It may be concluded that the ethanol
      technique provides a valid measure of changes in local skeletal muscle blood
      flow. The data furthermore show that a linear increase in thigh skeletal muscle
      blood flow exists during the studied protocol of intermittent isometric
      contractions.

PMID- 8306548
TI  - Haemodynamics of recovery after strenuous exercise in physically trained
      hypertensive and normotensive subjects.
AB  - 1. Central and peripheral post-exercise haemodynamics were studied in 18
      physically trained male subjects (10 hypertensive and eight normotensive)
      engaging in sports activities for 3-5 h/week. After a preliminary multistage
      bicycle ergometric test to evaluate their maximal oxygen consumption and
      anaerobic threshold, they underwent prolonged exercise at anaerobic threshold in
      the semi-supine position at 30% grade until exhaustion (mean duration 60.0 +/-
      16.7 min in the normotensive subjects and 61.0 +/- 5.7 min in the hypertensive
      subjects, not significant). During the recovery time, intra-arterial blood
      pressure, echocardiographic cardiac output and indium-gallium strain-gauge
      plethysmographic peripheral flow were measured, and total, forearm and leg
      peripheral resistances were calculated respectively from mean blood
      pressure/cardiac output and mean blood pressure/peripheral resistance. 2.
      Systolic blood pressure was decreased during the entire recovery period in
      comparison with the baseline values (-8.4 mmHg, -43.8 mmHg and -39.7 mmHg at the
      1st, 5th and 10th min in the hypertensive subjects, P = 0.001, P = 0.0001 and P =
      0.0001 respectively; -18.8, -25.5 and -24.1 mmHg in the normotensive subjects,
      not significant, P = 0.01 and P = 0.01, respectively) without any significant
      difference between the two groups, whereas the reduction in diastolic blood
      pressure was not statistically significant. Peripheral flow increased and
      peripheral resistance decreased in parallel in the forearm and the leg and showed
      similar trends in the hypertensive subjects and the normotensive subjects. The
      increase in cardiac output and left ventricular ejection fraction and the
      decrease in total resistance were also similar in the two groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8306549
TI  - Platelet catecholamine concentrations after short-term stress in normal subjects.
AB  - 1. Four studies were designed to test the hypothesis that platelet catecholamine
      levels may provide a stable index of circulating plasma catecholamine
      concentrations, and that these are unaffected by acute elevations of plasma
      levels with physical and psychological stress. 2. To assess the biological
      variability within individuals, ten subjects were sampled on five occasions over
      8-30 h. The intra-individual coefficients of variation for plasma and platelet
      noradrenaline levels were 19.5 +/- 10% and 9.5 +/- 4.2%, respectively, and for
      plasma and platelet adrenaline levels 48.3 +/- 22% and 25.3 +/- 8.4%,
      respectively. 3. Three other studies investigating the response to physical and
      psychological stress were performed. In the first study, plasma and platelet
      catecholamine levels were studied in 12 healthy subjects before and after bicycle
      ergometry. Plasma catecholamine concentrations increased [noradrenaline by +346
      +/- 323% (P = 0.002) and adrenaline by +314 +/- 352% (P = 0.003)], whereas
      platelet concentrations showed little change [noradrenaline +4 +/- 18% (P = 0.94)
      and adrenaline +38 +/- 116% (P = 0.67)]. 4. In the study, catecholamine
      concentrations were measured in eight subjects after hand immersion in iced
      water. Plasma noradrenaline concentrations increased significantly (+58 +/- 19%,
      P = 0.001), but no significant change was found in plasma adrenaline
      concentrations (+8 +/- 44%, P = 0.48). Platelet catecholamine concentrations
      showed no significant change (noradrenaline +15 +/- 15%, P = 0.052, and
      adrenaline 19 +/- 82%, P = 0.84). 5. In the third study, catecholamine
      concentrations were measured in 22 medical students before and after their end-of
      year examination.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306550
TI  - Cold-induced increases in erythrocyte count, plasma cholesterol and plasma
      fibrinogen of elderly people without a comparable rise in protein C or factor X.
AB  - 1. Six elderly (66-71 years) and six young (20-23 years) subjects (half of each
      group women) were cooled for 2 h in moving air at 18 degrees C to investigate
      possible causes of increased mortality from arterial thrombosis among elderly
      people in cold weather. Compared with thermoneutral control experiments, skin
      temperature (trunk) fell from 35.5 to 29.5 degrees C, with little change in core
      temperature. 2. Erythrocyte count rose in the cold from 4.29 to 4.69 x 10(12)/l,
      without a change in mean corpuscular volume, indicating a 14% or 438 ml decline
      in plasma volume; increased excretion of water, Na+ and K+ accounted for loss of
      only 179 ml of extracellular water. 3. Plasma cholesterol and fibrinogen
      concentrations rose in the elderly subjects from 4.90 mmol/l and 2.97 g/l
      (control) to 5.45 mmol/l and 3.39 g/l in the cold, and in the young subjects from
      3.33 mmol/l and 1.84 g/l (control) to 3.77 mmol/l and 2.07 g/l in the cold.
      Increases were significant for the elderly subjects, the young subjects and the
      group as a whole, except for cholesterol in the young subjects, and all were
      close to those expected from the fall in plasma volume. 4. Plasma levels of
      Protein C and factor X did not increase significantly in the cold in the elderly
      subjects, young subjects, or the group as a whole. 5. The results suggest that
      loss of plasma fluid in the cold concentrates major risk factors for arterial
      thrombosis, while small molecules, including protective Protein C, redistribute
      to interstitial fluid.

PMID- 8306552
TI  - Effect of induced bronchoconstriction on nasal airflow resistance in patients
      with asthma.
AB  - 1. Reflex bronchial changes have been demonstrated after nasal stimulation in
      both man and experimental animals. The existence of a pulmonary-nasal reflex is
      less established. We have examined whether induced narrowing of the intrathoracic
      airways leads to increases in nasal airflow resistance (Rnaw) in patients with
      asthma. 2. We have used a non-invasive forced oscillation method to measure total
      respiratory resistance (Rrs) at 8 Hz during tidal breathing sequentially via the
      nose (Rrs, na) and via the mouth (Rrs, mo) and derived Rnaw by subtracting Rrs,
      mo from Rrs, na. We examined whether changes in Rnaw occurred when increases in
      Rrs, mo were induced by inhaling histamine aerosol via the mouth with the nose
      occluded in 11 patients with stable, mild asthma (six males, age 28.1 +/- 2.1
      years, forced expiratory volume in 1 s 97 +/- 6% of predicted, means +/- SEM).
      Six of the patients had a history of rhinitis. The patients were first challenged
      with doubling concentrations of histamine via a dosimeter to establish the dose
      which reduced the forced expiratory volume in 1 s by > or = 20%. Two hours later
      when the forced expiratory volume in 1 s had returned to baseline, they were
      challenged with saline and again 2 h later with the concentration of histamine
      that had earlier caused a > or = 20% fall in the forced expiratory volume is 1 s.
      3. Between 0.5 and 10 min after histamine inhalation, a sustained increase in
      Rrs, mo was achieved with mean increases averaging 68-77% above baseline over
      this period (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306551
TI  - Pretreatment with methylprednisolone in coronary artery bypass grafting
      influences the levels of histamine and tryptase in serum but not in
      bronchoalveolar lavage fluid.
AB  - 1. The presence of histamine and tryptase in serum during and after coronary
      artery bypass grafting may be an indication of the induction of inflammation. 2.
      One group of patients received no glucocorticoids and a second group received
      methylprednisolone before extracorporeal circulation. In the steroid group no
      effects were seen on the basal levels of histamine (2.84 +/- 0.12 ng/ml) and
      tryptase (0.50 +/- 0.05 ng/ml) during and after surgery. In the other group two
      peak levels of histamine were observed: one at 10 min after starting
      extracorporeal circulation (4.19 +/- 1.79 ng/ml) and another at 4 h after surgery
      (8.26 +/- 4.85 ng/ml). In this group tryptase was only elevated during the period
      of extracorporeal circulation (1.54 +/- 0.16 ng/ml). 3. There were no differences
      between the two groups in complement activation. C3a levels rose to 170 +/- 8%
      and 180 +/- 10% of the initial value in the steroid and non-steroid group,
      respectively. 4. It was concluded that during surgery mast cells were activated,
      but since tryptase levels decreased in the post-operative period, the second
      increase in the histamine level can be explained by activation of basophils or by
      an unknown mechanism for the release of histamine but not tryptase by mast cells.
      5. In the bronchoalveolar lavage fluid the levels of histamine and tryptase
      showed no differences between the two groups of patients, but histamine was
      enhanced compared with normal levels.

PMID- 8306553
TI  - Rates of change in peak expiratory flow and in diurnal variation in peak flow in
      patients recovering from acute severe asthma.
AB  - 1. The rates of change in mean peak expiratory flow and in diurnal variation in
      peak flow were compared in 14 patients recovering from acute severe asthma. 2.
      Peak expiratory flow was measured on hospital admission, and at 6-hourly
      intervals for the next 3 weeks. 3. Diurnal variation in peak flow was assessed by
      measuring the following: amplitude (the highest minus the lowest peak expiratory
      flow during any given 24 h period), amplitude % mean (the highest minus the
      lowest peak expiratory flow during any given 24 h period divided by the mean peak
      expiratory flow over that period) and residual amplitude (the maximum variation
      about the mean peak expiratory flow during any given 24 h period). 4. Plots of
      diurnal variation in peak flow and peak expiratory flow against time were
      constructed for each patient. To enable comparison of changes in peak expiratory
      flow and diurnal variation in peak flow the data were transformed. 5. The rate of
      change for mean peak expiratory flow and for the three measures of diurnal
      variation in peak flow was assessed by fitting an exponential function to each
      set of data, and calculating the slope of the exponential curve halfway through
      the period of observation (10.5 days). 6. Median (range) slope for peak
      expiratory flow was 0.055 (0-2.57). The comparable value for amplitude was -3.15
      (-1.27 to -4.22) (absolute median values compared, P = 0.0029), for amplitude %
      mean was -1.87 (-0.18 to -5.95) (P = 0.012) and for residual amplitude was -1.43
      (-0.62 to -3.09) (P = 0.033).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306554
TI  - Heterogeneity of human gallbladder mucin in bile.
AB  - 1. Human gallbladder mucin has been implicated to play a role in gallstone
      disease. In spite of this fact relatively little is known about the structure of
      human gallbladder mucin. In this study we have investigated the possible
      heterogeneity of mucin. For this purpose polyclonal and monoclonal antibodies
      against gallbladder mucin were raised. All antibodies reacted primarily with
      carbohydrate antigenic determinants. With these antibodies the immunoreactivity
      of gallbladder mucin from 60 patients with cholesterol gallstones and 20 subjects
      without stones was screened. In addition, reactivity with several lectins was
      studied. 2. Considerable heterogeneity was found with both antibody and lectin
      typing, but there was no significant difference in heterogeneity between mucin
      from patients with gallstones and control subjects. Immunoblotting revealed that
      there was similarity between the reaction of the polyclonal antibody and the
      Helix pomatia agglutinin. All mucin preparations reacting with the polyclonal
      antibody also bound to Helix pomatia agglutinin. Nineteen of the 21 reacting
      mucins (90%) were from patients with blood group A (18 patients) or AB (one
      patient) and expression of A antigen could be demonstrated on the mucin of these
      patients. The resulting two reacting mucins were from patients with type O.
      However, expression of the blood group antigen could not account for the lack of
      reactivity of the mucin of other patients. The Helix pomatia agglutinin partially
      blocked the reactivity of the polyclonal antibody, whereas anti-A antibody did
      not show inhibition, indicating that more than only blood group A epitopes were
      recognized by this antibody. 3. We conclude that considerable patient to patient
      heterogeneity of human gallbladder mucin exists.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306555
TI  - Heterogeneity of human biliary mucin: functional implications.
AB  - 1. Human gallbladder mucin has been implicated as playing a role in the
      pathogenesis of gallstones. In previous studies no differences have been found in
      the content or composition of mucins derived from control bile or cholesterol
      gallstone bile. Until now, no differences were also found between these two
      groups of mucins with regard to their ability to cause cholesterol nucleation. In
      the accompanying paper we have reported that there is a strong heterogeneity of
      gallbladder mucins derived from individual patients (M. J. A. van Wijland, J. H.
      Klinkspoor, L. Th. de Wit, R. P. J. Oude Elferink, G. N. J. Tytgat and A. K.
      Groen, Clin Sci 1994; 86: 67-74). In the present study we further investigated a
      possible patient to patient heterogeneity of mucin by means of immunological and
      functional characterization of mucins isolated from hepatic bile of six different
      patients with gallstones. 2. Considerable heterogeneity was found. Two of the
      mucins barely reacted with a polyclonal anti-mucin antibody, whereas the other
      four mucins reacted very strongly. Lectin-binding studies indicated that the
      glycans of these two mucins expressed less D-N-acetylgalactosamine residues than
      the other four mucins. This was confirmed by analyses of the glycan compositions.
      These studies furthermore indicated that the glycans were of the O-linked type,
      contained alpha-D-N-acetylglucosamine and were fucosylated, sialylated and
      sulphated to different extents. Except for a strong heterogeneity in the sugar
      composition of the mucins, heterogeneity was also found in the biological
      activity of the mucins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306556
TI  - Glucose turnover in pregnant women with acute malaria.
AB  - 1. Hypoglycaemia is a serious complication of falciparum malaria, especially in
      pregnant patients. To investigate malaria-associated changes in glucose
      metabolism in pregnancy, steady-state [6,6-2H2] glucose turnover and clearance
      were measured in 10 women (eight with uncomplicated falciparum malaria and two
      with vivax malaria at 16-30 weeks gestation) before treatment, after intravenous
      quinine infusion (patients with falciparum malaria) and in convalescence. 2.
      Admission basal plasma glucose concentrations were higher than those in
      convalescence [median (range); 4.8 (3.6-7.0) versus 4.0 (3.6-4.6) mmol/l, P =
      0.02], and there was a significant fall during initial quinine treatment in
      patients with falciparum malaria [5.0 (4.3-7.6) to 3.6 (3.2-5.4) mmol/l, P <
      0.01]. Basal plasma insulin levels were comparable at presentation and follow-up
      (P = 0.35) and rose an average of only 2m-units/l during quinine infusion (P <
      0.05). Pretreatment glucose turnover rates [3.37 (2.57-4.16) mg min-1 kg-1] were
      comparable with those found in a previously reported study of non-pregnant
      severely ill patients [3.22 (2.12-4.82) mg min-1 kg-1, n = 11] and correlated
      significantly with the admission parasitaemia (P < 0.025). In the eight patients
      with falciparum malaria, there was a significant fall in turnover during
      intravenous quinine infusion [3.42 (2.58-4.16) to 2.66 [1.94-3.94) mg min-1 kg-1]
      whereas clearance did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306558
TI  - Family practice.

PMID- 8306557
TI  - Nitrogen homeostasis in man: influence of protein intake on the amplitude of
      diurnal cycling of body nitrogen.
AB  - 1. The diurnal nature of nitrogen (N) homoeostasis was investigated in adults fed
      increasing protein intakes. N balance was estimated during a 48 h period of
      consecutive 12 h periods of feeding hourly meals and fasting, after 12 days of
      adaptation to diets containing 0.36 +/- 0.01, 0.77 +/- 0.03, 1.59 +/- 0.08 and
      2.31 +/- 0.65 g of protein day-1 kg-1. N losses were determined from measured
      urinary N excretion corrected for changes in the body urea pool, and estimated
      faecal and miscellaneous losses. [13C]Leucine and [2H5]phenylalanine balances
      were measured during a primed, continuous infusion of the two amino acids during
      the fasting and feeding phase on the second day. 2. Increasing fasting N losses
      were observed (47 +/- 7, 60 +/- 6, 95 +/- 15 and 140 +/- 36 mg day-1 kg-1) on the
      four intakes, with corresponding increasing fed gains of 8.2 +/- 3.9, 40.2 +/-
      7.1, 112 +/- 24 and 180 +/- 56 mg day-1 kg-1. 3. Increasing fed-state amino acid
      gains with increasing protein intake were observed with both [13C]leucine and
      [2H5]phenylalanine, whereas increasing fasting amino acid losses were confirmed
      with [13C]leucine. 4. The N equivalent of the leucine oxidation rate was mostly
      in the range of 10-50% lower than expected from the N excretion rates. This may
      reflect the timing of the amino acid balance measurements and non-uniform rates
      of gain and loss throughout the diurnal cycle. 5. We conclude on the basis of
      both N and amino acid balances that the amplitude of the diurnal cycling of body
      protein N in human adults increases with increasing dietary protein intake. Thus
      one component of the protein requirement for N balance reflects a demand for
      repletion of fasting losses which increases with increasing habitual protein
      intake.

PMID- 8306559
TI  - 9 Health Fair.

PMID- 8306560
TI  - The new direction: a report/update from the Colorado Foundation for Medical Care.

PMID- 8306561
TI  - O.S.H.A. news.

PMID- 8306562
TI  - FDA reiterates personal-use importation policy to buyers' clubs.

PMID- 8306563
TI  - Surveillance study adds to database on seroconversion rates and zidovudine use
      after occupational exposures.

PMID- 8306564
TI  - Guidelines for release of clinical alerts set.

PMID- 8306565
TI  - Flumazenil: a benzodiazepine antagonist.
AB  - The mechanism of action, pharmacokinetics, and use of flumazenil in
      benzodiazepine overdose, as well as in the management of other disease states,
      are reviewed. Flumazenil interacts at the central benzodiazepine receptor to
      antagonize or reverse the behavioral, neurologic, and electrophysiologic effects
      of benzodiazepine agonists and inverse agonists. Flumazenil has been studied for
      a variety of indications, including as an antidote to benzodiazepine overdose and
      for awakening of comatose patients, reversal of sedation after surgery and in
      critically ill patients, and management of hepatic encephalopathy. It improves
      the level of consciousness in patients with benzodiazepine overdose; however,
      resedation may occur within one to two hours after administration, so repeated
      doses or a continuous infusion may be required to maintain therapeutic efficacy.
      It appears to be effective in reversing sedation induced by midazolam or
      diazepam, and case reports suggest that it is useful in awakening comatose
      patients, although its clinical utility is questionable. Flumazenil has proved
      useful in reversing conscious sedation in critically ill patients, although
      response may be dose dependent. Animal models indicate that flumazenil is of some
      benefit in hepatic encephalopathy, but until well-designed clinical trials are
      conducted, hepatic encephalopathy must be considered an investigational
      indication for flumazenil. Adverse reactions include CNS manifestations,
      resedation, cardiovascular effects, seizures, and alterations in intracranial
      pressure and cerebral perfusion pressure. Hepatic dysfunction results in a
      substantial change in the pharmacokinetic profile of flumazenil; therefore,
      dosage adjustment may be necessary in patients with hepatic dysfunction or in
      those receiving medications that alter flumazenil metabolism. Flumazenil has been
      shown to reverse sedation caused by intoxication with benzodiazepines alone or
      benzodiazepines in combination with other agents, but it should not be used when
      cyclic antidepressant intoxication is suspected. It may be beneficial after
      surgery when benzodiazepines have been used as part of anesthesia and after a
      diagnostic or surgical procedure when assessment of CNS function is necessary.

PMID- 8306566
TI  - Pharmacologic management of cystic fibrosis.
AB  - Standard pharmacologic management of cystic fibrosis is discussed and the role of
      new agents in the treatment of this disease is explored. Cystic fibrosis is a
      recessive, fatal genetic disease involving multiple organ systems, in which
      patients develop pancreatic insufficiency, malabsorption, and repeated pulmonary
      infections. Pharmacotherapy to date has included broad-spectrum antimicrobials
      and aggressive nutritional management with microencapsulated pancreatic enzymes.
      Acute pulmonary exacerbations, caused by Pseudomonas aeruginosa, require
      combination i.v. antimicrobial therapy for 14 to 21 days. With the recent
      discovery of the genetic defect responsible for cystic fibrosis, as well as the
      cellular mechanism, new pharmacologic approaches are being explored to improve
      treatment. Aerosolized amiloride is being tested to modify the basic defect in
      the chloride channel. Dornase, a new mucolytic, is used to decrease sputum
      viscosity and increase mucociliary clearance. Leukoprotease inhibitors are
      currently being evaluated for decreasing the acute inflammatory reaction in the
      lung. Gene therapy has been promising, but its role in the management of cystic
      fibrosis is many years away. Drug therapy for cystic fibrosis has been primarily
      directed at treating infections with antibiotics and supplementing digestive
      enzymes and vitamins. New agents and gene therapy may substantially change the
      morbidity and mortality of this disease.

PMID- 8306568
TI  - Judicious use of flumazenil.

PMID- 8306567
TI  - Estimation of creatinine clearance in patients with gynecologic cancer.

PMID- 8306569
TI  - Pleurodesis with solution prepared from quinacrine hydrochloride tablets.

PMID- 8306570
TI  - Criteria for use of cyclosporine in adult transplant recipients.

PMID- 8306571
TI  - [Behcet disease. Description of three cases with manifestations at multiple
      localizations. Current status of understanding].
AB  - On the basis of their personal experience and of a review of the literature, the
      authors stress that in view of its multiple localizations Behcet's disease must
      be considered a systemic disorder. The authors further stress the importance of
      recognizing by new and more suitable diagnostic methods all atypical
      localizations of this pathology in order to ensure early detection and
      appropriate management.

PMID- 8306572
TI  - Therapy of chronic non-A, non-B hepatitis with alpha interferon. A comparison
      between natural and recombinant alpha interferon.
AB  - We studied the effects of two different types of interferon alpha (natural
      interferon from human leukocytes vs. recombinant interferon 2b) in 64 patients
      with chronic Non-A, Non-B hepatitis; other finalities were: definition of the
      optimal duration of therapy with interferon alpha (IFN alpha), entity of side
      effects, cost-benefit ratio. Patients were randomly assigned to one of three
      groups, according to duration of IFN alpha treatment: Group I was treated for 12
      months, Group II for six months, Group III for 3 months. Each group consisted of
      two subgroups, divided on the basis of the type of IFN used: subgroup A was
      administered natural IFN alpha, and subgroup B received recombinant IFN alpha 2b.
      Each patients was given 3 million units of IFN alpha by intramuscular injection
      on alternate days. At the end of treatment, a decrease in serum ALT activity was
      achieved in 39 cases (65%). The response rate was higher in Group I (89%) than in
      Group II (54%) and Group III (55%). Natural and recombinant IFN alpha 2b induced
      similar effects in patients treated for twelve months (Group I); recombinant IFN
      was more effective than natural IFN alpha in patients treated for six and three
      months. We conclude that the 12-month treatment with 3 million units of
      intramuscular recombinant IFN alpha, administered on alternate days, might be the
      optimal therapy schedule. This proposal is also supported by the evaluation of
      the cost benefit ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306573
TI  - [Binswanger disease. Tomographic picture and clinical correlations].
AB  - The authors explore the correlation between the neuroradiologic and clinical
      patterns of "subcortical arteriosclerotic encephalopathy" (SAE) or Binswanger's
      disease. The typical neuroradiologic pattern has been found in 62 of the 1804 CT
      scans of the department's archive. Available patients were enrolled for
      neuropsychologic evaluation. The authors point out that there is no correlation
      whatever between severity of the CT pattern and findings of psychological
      decline. Therefore SAE may be considered merely a neuroradiologic pattern. The
      discrepancy between neuroradiologic and clinical pattern depends on the
      individual history of every single patient as well as on the quality of the
      neuronal cells involved in vascular pathology. It may in fact be thought that the
      injury to command neurones plays a fundamental role in bringing about the
      psychopathologic picture.

PMID- 8306574
TI  - [Efficacy of percutaneous administration of anti-inflammatory drugs in swimmers
      and water-polo players].
AB  - It can be concluded from the research reported above that diclofenac
      diethylammonium (NSAID) in cases of professional swimmers and waterpolo players
      who have either an ache or suffered a severe hit, when applied externally offers
      rapid and excellent results.

PMID- 8306575
TI  - [Current views on the pathogenesis and therapy of ankylosing spondylitis].
AB  - Ankylosing spondylitis is a frequent and disabling inflammatory chronic disease,
      that affects mainly young men. In this paper the authors reviewed the
      pathogenetic mechanism and pharmacological and physical treatment. Nowadays the
      pathogenesis of ankylosing spondylitis is considered similar to that of reactive
      arthritis. The management of each patient should take into account the different
      aspects of the disease; therefore it should be individually designed.

PMID- 8306576
TI  - [Clinical experience with the use of piroxicam in fast-dissolving sublingual
      capsules in acute recurrent osteoarthritis].
AB  - Open, non comparative study to evaluate the efficacy and safety of piroxicam Fast
      Dissolving Dosage Form (FDDF) for sublingual administration in treatment of
      reacutized osteoarthritis. Fifty-four patients with flare-ups of osteoarthritis
      involving various joints were enrolled in the study. They were treated with 20
      mg/die piroxicam sublingual tablets for a total of 4 weeks. Drug efficacy was
      evaluated on the basis of the variation of spontaneous pain, pain on passive
      motion, functional limitation and capacity of performing a specific activity.
      Intensity of spontaneous pain on the first day showed a statistically significant
      improvement (p < 0.0001) only 15 minutes after the drug administration. This
      improvement in pain intensity increased until day 3. All other efficacy
      parameters showed a statistically significant improvement (p < 0.0001) 7 days
      after the beginning of treatment. Local and systemic tolerability was good. No
      patient showed local side effects; only 6 patients experienced systemic side
      effects. In conclusion, piroxicam sublingual tablets for treatment of
      osteoarthritis flare-ups showed analgesic efficacy already 15 minutes after drug
      administration, and good anti-inflammatory efficacy with good local and systemic
      tolerability.

PMID- 8306577
TI  - [Sterilization with ethylene oxide].
AB  - In the above brief note, the authors discuss the validity of sterilization with
      ethylene oxide in hospital. The use of this agent requires most accurate
      attention by the operator and precise specific indication in view of the many
      negative factors which limit its widespread use, above all its marked toxicity
      and the fact that it is not easy to handle.

PMID- 8306578
TI  - [Current role of computerized tomography and prospectives of the use of magnetic
      resonance in the diagnosis of aortic abdominal aneurysms and evaluation of their
      complications].
AB  - In this work we discussed the role of conventional radiology, ultrasonography
      (US), angiographic study, CT scan and MR imaging in the diagnosis of abdominal
      aortic aneurysms and their complications. US is the most suitable technique for
      screening and follow-up study of aortic aneurysms. Unfortunately it is not so
      reliable in the study of visceral arteries and in fat patients. Aortic
      angiography is the most useful method for the study of visceral arterial
      branches, but it does not show the phlogistic changes as well as the peripheral
      thrombotic alterations within the lesion. TC scan is also a useful technique in
      the study of aortic aneurysm, although it is not so accurate in detecting the
      visceral arterial branches. Finally, we think that MR imaging is the most
      reliable method for the diagnosis of aortic aneurysm. Movement artifact and lack
      of information due to the poor visualization of calcifications are still the
      principal limits of this technique.

PMID- 8306579
TI  - [Use of cholinesterase inhibitors in Alzheimer disease].
AB  - According to the cholinergic theory of Alzheimer's disease, the cognitive failure
      depends on a deficit in acetylcholine. The study reported above examines the
      efficacy and tolerability of cholinesterase inhibitors, such as tetrahydroamino
      acridine (THA), for the management of this pathology.

PMID- 8306580
TI  - [Hearing and the brain. Research at 5 Italian Centers].

PMID- 8306581
TI  - Diabetes mellitus and employment discrimination.

PMID- 8306582
TI  - Cohorts of insulin-treated patients with diabetes.

PMID- 8306583
TI  - Gestational diabetes: a challenge for the future.
AB  - It is well established that pregnancy is associated with temporary changes in
      maternal metabolism which include a decrease in maternal insulin sensitivity to
      values similar to those associated with Type 2 diabetes. Fasting glucose
      concentrations fall throughout pregnancy, postprandial values rise. The
      maintenance of glucose tolerance in pregnancy requires a two- to three-fold
      increase in postprandial maternal insulin secretion. Glucose intolerance develops
      in women unable to compensate for the metabolic changes incurred by pregnancy.
      Increasing maternal hyperglycaemia is associated with increasing pregnancy
      morbidity and an increased likelihood of subsequent diabetes in the mother. In
      addition, maternal hyperglycaemia has a direct effect on the development of the
      fetal pancreas and is associated with an increased susceptibility to future
      diabetes in the infant, an effect which is independent of genetic factors.
      Gestational diabetes mellitus (GDM) is defined as glucose intolerance first
      recognized in pregnancy, and by definition includes a small number of women with
      previously unrecognized diabetes or impaired glucose tolerance (IGT). Figures on
      the prevalence of GDM vary between maternity units, depending on screening
      methods and the ethnic distribution of the populations. However, in a
      comprehensive study of a multi-ethnic antenatal population in inner London, UK it
      was found that only 2% of pregnant women develop significant glucose intolerance.
      Obstetricians and physicians debate the importance of identifying this 2% of
      women. The lack of agreed criteria for diagnosing gestational diabetes and the
      questionable obstetric benefits of treating all women with mild disturbances of
      glucose tolerance in pregnancy has resulted in few UK centres undertaking
      universal screening for GDM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306584
TI  - Does the prepubertal duration of diabetes influence the onset of microvascular
      complications?
AB  - This study investigated the relationship between the development of diabetic
      retinopathy and pubertal status at onset of diabetes in 521 Type 1 diabetic
      patients diagnosed between 1950 and 1985. Pubertal status was based on age at
      onset (girls > or = 11 years and boys > or = 12 years). Retinopathy (all forms)
      developed in 112 patients (21.5%; 65 background and 47 proliferative
      retinopathy). For subjects diagnosed in either the prepubertal or postpubertal
      period, a similar proportion survived without developing retinopathy for any
      given duration of diabetes (chi 2 = 0.3822, p = 0.54). However, if only the
      postpubertal duration of diabetes is considered, then the proportion of patients
      surviving without retinopathy was significantly less for those diagnosed in the
      prepubertal period (chi 2 = 14.2, p = 0.002). This study suggests that the
      prepubertal duration of diabetes is an important phase and that the years prior
      to puberty do contribute to the risk of developing microvascular injury.

PMID- 8306585
TI  - Abnormal digital pressure measurements in diabetic neuropathic foot ulceration.
AB  - The diabetic neuropathic ulcer is typically slow to heal and recurrent.
      Macrovascular insufficiency is usually excluded as foot pulses are present and
      ankle:brachial pressure ratios are not decreased. These assessments cannot
      however exclude more distal vascular disease. Digital pressure measurements
      enable a reliable assessment of the distal peripheral vascular status to be made.
      The aim of this study was therefore to use toe pressures to assess the
      contribution of distal ischaemia in the pathogenesis of the neuropathic ulcer.
      Sixteen diabetic patients with recurrent neuropathic foot ulceration had their
      toe pressures compared to 10 neuropathic patients without a history of foot
      ulceration, 10 diabetic control subjects, and 11 normal subjects. Four non
      diabetic patients with neuropathy and foot ulceration were also assessed. All
      subjects had ankle:brachial pressure indices > or = 1. Toe pressure was assessed
      using laser Doppler flowmetry to record the return of skin blood flow. The
      toe:brachial pressure index (TBI) was then calculated. The diabetic patients with
      a history of recurrent neuropathic ulceration, had the lowest mean TBI, 0.63 +/-
      0.14 (SD), compared to the non-ulcerated diabetic neuropathy patients, the
      diabetic control subjects, and the normal subjects. 0.84 +/- 0.11, 0.82 +/- 0.1,
      and 0.81 +/- 0.07, p < 0.01, respectively. Three of the four non-diabetic
      patients with neuropathic foot ulceration also had an abnormally low TBI. Reduced
      toe pressure measurements are thus found to be associated with neuropathic foot
      ulceration. The contribution of distal ischaemia in the pathogenesis of the
      diabetic neuropathic foot ulcer needs to be evaluated.

PMID- 8306586
TI  - Changes in autonomic nervous function over a 5-year period in non-insulin
      dependent diabetic patients.
AB  - One hundred and eight non-insulin-dependent diabetic patients who had been tested
      for autonomic dysfunction in 1984/85 were re-evaluated 5 years later. Autonomic
      function was assessed by means of four cardiovascular tests (heart rate variation
      during deep breathing and standing, and blood pressure variation after standing
      and sustained handgrip). Eighteen subjects were lost to follow-up; in the 90
      patients who completed the study, both the deep breathing and the handgrip test
      significantly worsened (respectively from 13.7 +/- 7.8 to 11.6 +/- 6.3 beats min
      1 p < 0.01, and from 16.9 +/- 8.2 to 12.7 +/- 7.1 mmHg, p < 0.001), whereas both
      the 30:15 ratio and the variation of blood pressure on standing did not change.
      The impairment of a comprehensive evaluation score (from 2.5 +/- 1.7 to 3.0 +/-
      1.5; p < 0.05) also confirmed the gradual deterioration of autonomic function
      over the study period.

PMID- 8306587
TI  - Prevalence of QT prolongation in a type 1 diabetic population and its association
      with autonomic neuropathy. The Neuropathy Study Group of the Italian Society for
      the Study of Diabetes.
AB  - The prevalence of QT prolongation in a large random sample of Type 1 diabetic
      patients in Piemonte, Italy and its association with autonomic neuropathy were
      assessed. Three hundred and seventy-nine Type 1 diabetic patients (age 15-59)
      with (94, DAN+) and without (280, DAN-) autonomic neuropathy and 118 non-diabetic
      control subjects participated in the study. QT interval was measured on an ECG
      recorded at rest and QTc calculated according to Bazett's formula. QTc was
      greater than 0.440 s in 7.6% (95% CI 2.9-12.3) of control subjects, 25.6% (21.0
      30.0) of diabetic patients, 30.8% (21.5-40.1) of DAN+, 23.9% (18.9-28.9) of DAN-.
      QTc was greater than 0.460 s (mean + 2SD of QTc in control subjects) in 11.7%
      (8.5-14.9) of diabetic patients, 18.1% (10.3-25.9) of DAN+, 9.6% (6.2-13.0) of
      DAN-. QT was above the 95% upper limit for the control subjects in the plot of
      measured QT against RR interval in 21.4% (17.3-25.5) of diabetic patients, 26.6%
      (17.7-35.5) of DAN+, 19.3% (14.7-23.9) of DAN-. No correlation was found between
      QT interval and age or disease duration. The prevalence of QT prolongation was
      higher in diabetic patients than in control subjects and in DAN+ than in DAN-.

PMID- 8306588
TI  - The toxic effects of serum from patients with type 1 diabetes mellitus on mouse
      neuroblastoma cells: a new mechanism for development of diabetic autonomic
      neuropathy.
AB  - The pathogenesis of diabetic neuropathy is incompletely understood. The
      possibility that humoral neurotoxic factors contribute as a cause of diabetic
      neuropathy was tested by application of serum from patients with Type 1 and Type
      2 diabetes to mouse neuroblastoma cells, which have the characteristics of
      adrenergic neurons in culture. Serum from patients with Type 1 diabetes and
      somatic neuropathy significantly inhibited both proliferation and differentiation
      of neuroblastoma cells, while serum from patients with Type 1 diabetes but no
      symptoms of neuropathy and patients with Type 2 diabetes and neuropathy had no
      effect on proliferation, and serum from Type 2 patients only marginally inhibited
      differentiation. The effects of Type 1 diabetic serum could be reversed by pre
      absorption of the serum to neuroblastoma cells, and were independent of glucose
      levels. Immunoglobulins precipitated from the sera mimicked the effects of whole
      sera. These results suggest that Type 1 diabetes mellitus causes a change in
      serum composition, possibly related to autoimmunity, that is capable of
      contributing to adrenergic autonomic neuropathy in diabetic patients.

PMID- 8306589
TI  - Reproducibility of parameters for assessment of diabetic neuropathy. The French
      Group for Research and Study of Diabetic Neuropathy.
AB  - This study evaluated the reproducibility of nerve function assessment in a group
      of 132 diabetic patients with moderate peripheral polyneuropathy. Patients were
      investigated at the beginning and the end of the run-in period (a 1-month placebo
      period) of a multicentre trial of an aldose-reductase inhibitor (Ponalrestat).
      Reproducibility was evaluated by performing four types of tests: quantitative
      visual scales of symptoms, quantitative sensory assessment (vibration perception
      thresholds in medial malleolus and great toe, foot thermal perception threshold
      to hot and cold), electrophysiological investigations on the dominant side
      (conduction velocities and potential amplitudes of sensory and median motor
      nerve, sural and peroneal nerves, amplitudes of F waves of median motor and
      peroneal nerves) and cardiac autonomic tests (Valsalva, deep-breathing, lying-to
      standing). Reproducibility was poor for symptoms, thermal sensitivity, and
      potential amplitudes. It was satisfactory (total coefficient of variation < 50%)
      for all the other parameters and even very good (total variation coefficient <
      26%, intra-subject variation factors corresponding to < 56% of total variance)
      for velocities of sensory and median motor and peroneal nerves, the amplitudes of
      F waves and the three autonomic tests. For most of the parameters total variance
      was mainly related to inter-subject variability. However, inter-subject
      variability for the three cardiac autonomic tests was very low and at least one
      cardiac autonomic test was altered in all the patients. Inter-centre variability
      was low for all the parameters, except for action potential amplitudes and for F
      wave velocity of the median motor nerve. This study suggests those parameters
      that are appropriate for the assessment of diabetic neuropathy and for
      therapeutic trials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306590
TI  - Physiological, symptomatic and hormonal responses to acute hypoglycaemia in type
      1 diabetic patients with autonomic neuropathy.
AB  - The effects of peripheral autonomic neuropathy on the symptomatic, physiological,
      and hormonal responses to acute insulin-induced hypoglycaemia were studied in two
      groups of patients with Type 1 diabetes, matched for age, duration of diabetes,
      and prevailing glycaemic control. A group of eight patients who gave a history of
      normal awareness of hypoglycaemia and had normal cardiovascular autonomic
      function tests were compared to a group of six patients who had symptoms of
      autonomic dysfunction and gross abnormalities of cardiovascular autonomic
      function tests. An additional two patients with autonomic neuropathy who also had
      hypoglycaemia unawareness were studied. Acute hypoglycaemia was induced by
      intravenous infusion of insulin (2.5 mU kg-1 min-1) and the onset of the acute
      autonomic reaction (R) was identified objectively by the sudden rise in heart
      rate and onset of sweating. Cognitive function and hypoglycaemia symptom scores
      were estimated serially, and plasma counterregulatory hormones were measured.
      Acute autonomic activation was observed to occur in all subjects in response to
      hypoglycaemia and commenced at similar venous plasma glucose concentrations in
      both groups (neuropathic patients: 1.6 +/- 0.2 mmol l-1 vs non-neuropathic
      patients 1.6 +/- 0.2 mmol l-1, p = 0.9,). In the neuropathic patients plasma
      adrenaline responses were significantly lower at all time points from time R
      until time R + 30 min (MANOVA for repeated measures, F = 19.4, p <
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306591
TI  - Different acute and chronic effects of acipimox treatment on glucose and lipid
      metabolism in patients with type 2 diabetes.
AB  - To study whether therapeutic reduction of non-esterified fatty acids (NEFA) can
      be used to improve glucose metabolism, we administered the antilipolytic agent,
      acipimox, 250 mg four times daily for 4 weeks in eight obese Type 2 diabetic
      patients. Glucose and NEFA metabolism were assessed before and after treatment
      with a two-step euglycaemic hyperinsulinaemic clamp (0.25 and 1 mU kg-1 min-1
      insulin) combined with infusions of [3-3H] glucose and [1-14C] palmitate. Three
      days of acipimox treatment reduced 24-h serum NEFA levels by 10%, but the
      difference disappeared after 4 weeks of treatment mainly due to a two-fold rise
      in morning NEFA concentrations (p < 0.01). After 3 days of acipimox treatment,
      fasting and 24-h plasma glucose and serum triglyceride concentrations were
      significantly reduced (p < 0.05), but no longer after 4 weeks of treatment.
      Despite the rebound rise in NEFA, acute administration of acipimox still
      inhibited both oxidative and non-oxidative NEFA metabolism in the basal state (p
      < 0.01-0.001) and during insulin infusion (p < 0.05-0.001). Inhibition of NEFA
      metabolism was associated with increased insulin-stimulated glucose uptake (from
      3.56 +/- 0.28 to 5.14 +/- 0.67 mumol kg-1 min-1, p < 0.05), mainly due to
      stimulation of non-oxidative glucose disposal (from 1.74 +/- 0.23 to 3.03 +/-
      0.53 mumol kg-1 min-1, p < 0.05). In conclusion, acipimox administered acutely
      inhibits NEFA appearance (lipolysis), which is associated with improved glucose
      uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306592
TI  - Wine for type 2 diabetic patients?
AB  - To ensure an acceptable quality of life for Type 2 diabetic patients, the food
      recommendations have to be as liberal and individualized as possible.
      Unfortunately, disagreements exists about the consumption of different types of
      wine. Diabetic patients are advised by some to restrain their wine intake and to
      use dry wine containing little carbohydrate, while others are more liberal. The
      purpose of this study was to evaluate the effects of dry and sweet wine on the
      glycaemic control in Type 2 diabetes. Twelve diabetic patients consumed a light
      meal with either 300 ml tap water 300 ml dry white wine, 300 ml sweet white wine
      with ethanol added or 300 ml dry white wine with glucose added. Similar glucose,
      insulin, and triglyceride responses were obtained in all four situations. There
      was a greater suppression of the free fatty acid levels in the three situations
      with wine as compared with water (p < 0.001). This effect may be caused by an
      attenuation of the free fatty acid mobilization and esterification of free fatty
      acids to triglycerides induced by alcohol. Our results indicate that patients
      with well-controlled Type 2 diabetes can drink moderate amounts of wine with
      meals without risking acute deterioration of glycaemic control. Whether the wine
      is dry or sweet has no impact on the glycaemic control.

PMID- 8306593
TI  - Prescribed versus unrestricted carbohydrate diets in children with type 1
      diabetes.
AB  - The diets of 53 children over 8 years of age with diabetes mellitus were examined
      by 24 h recall. Thirty-seven had been on prescribed carbohydrate diets while 16
      had been on an unrestricted carbohydrate diet since diagnosis. The mean intakes
      of energy (prescribed 9.1 MJ, unrestricted 9.0 MJ, p = 0.66), carbohydrate
      (prescribed 259 g, unrestricted 251 g, p = 0.64), fat (prescribed 99.8 g,
      unrestricted 98.2 g, p = 0.84) and fibre (prescribed 29.2 g, unrestricted 31.0 g,
      p = 0.42) were not significantly different between the two groups. Both groups
      showed similar distribution of carbohydrate through the day and considerable day
      to day variation in their carbohydrate intake (coefficient of variation,
      prescribed 14.5%, unrestricted 14.1%, p = 0.87). Those on prescribed diet had a
      mean carbohydrate intake which exceeded their prescription by 36%. Both groups
      had above average fibre intake suggesting that qualitative advice was being
      followed. There were no significant differences between the two groups in
      metabolic control (HbA1 prescribed 12.4%, unrestricted 11.9%, p = 0.23), body
      mass index (prescribed 19.8 kg m-2, unrestricted 20.4 kg m-2) or insulin dosage
      (prescribed 1 unit kg-1 day-1, unrestricted 0.9 units kg-1 day-1). This study has
      shown no differences between prescribed and unrestricted carbohydrate diets.
      Qualitative, rather than quantitative advice may be more appropriate in the
      management of Type 1 diabetic children.

PMID- 8306594
TI  - What do people with diabetes want to talk about with their doctors?
AB  - A survey was conducted to establish the concerns of people with diabetes when
      they consult their doctors. A total of 225 people attending consecutively at the
      Manchester Diabetes Centre were invited to take part. Their concerns were
      assessed by a questionnaire administered immediately before consulting a doctor.
      Of the 220 (98%) respondents 53.6% had concerns about metabolic control; 31.8%
      had concerns which suggested cognitive or emotional problems in coming to terms
      with their diabetes; 20.5% and 22.7% had concerns related to organ involvement
      and medication, respectively; 11.8% expressed no concerns. Women who were
      concerned about metabolic control and organ involvement were younger than women
      who were not (p < 0.001, and p = 0.004, respectively). Men who were concerned
      about medication were younger than men who were not (p = 0.002). The concerns of
      men diagnosed for < or = 10 years were more likely to suggest difficulty in
      adjusting to the disease than those who had been diagnosed for longer (p =
      0.007). Women diagnosed for < or = 10 years were more likely to be concerned
      about metabolic control than those diagnosed for longer (p = 0.018). Both men and
      women diagnosed for > 10 years, were more likely to be concerned about medication
      than those diagnosed for a shorter time (p = 0.025). Ethnicity did not seem to
      influence the outcomes. The significant proportion of people who have concerns
      which suggest difficulty in adjusting to the disease, the gender differences, and
      the changes over time suggest the need for more detailed research into those
      concerns.

PMID- 8306595
TI  - Pre-mixed insulin delivered by disposable pen in the management of children with
      diabetes.
AB  - Pre-mixed insulin preparations are being used increasingly in the management of
      children with IDDM. Recently this form of insulin has been produced in a
      disposable insulin pen device. An open randomized 3-month crossover study was
      conducted to compare glycaemic control on a self-titrating insulin regimen with a
      pre-mixed (30:70) preparation, both given twice daily. The pre-mixed preparation
      was delivered by disposable pen. Forty children (age range 7-16 yr) entered the
      study. Mean +/- SEM glycosylated haemoglobin (HbA1 %) at the start of the study
      (13.1 +/- 0.6) compared with values at the end of the self-titrating (11.8 +/-
      0.5) and pre-mixed periods (12.5 +/- 0.5), as well as blood glucose profiles
      taken at 3-weekly intervals, showed no significant change. Fourteen of the
      children were on insulin ratios other than 30:70 (range 10:90 to 50:50) and were
      unaffected by the switch (HbA1 at the start of the study 12.7 +/- 1; at the end
      of the self-titrating 11.5 +/- 0.8; and pre-mixed period 12.5 +/- 0.8). Twenty
      one children continued on the pen for a further 12 months with no deterioration
      in control (HbA1 at the beginning and end of this period being 11.9 +/- 0.7 and
      11.0 +/- 0.7, respectively). The children (95%) preferred the disposable pen and
      pre-mixed insulin regimen. Switching to pre-mixed insulin, while not improving,
      has no detrimental effect on glycaemic control.

PMID- 8306596
TI  - Evaluation of glycaemic control limits using the Ames DCA 2000 HbA1c analyser.
AB  - The Ames DCA 2000 is a benchtop analyser that measures HbA1c by an agglutination
      inhibition immunoassay using a monoclonal antibody. Laboratory and nursing staff
      measured HbA1c on-site in 78 patients with Type 1 diabetes at the outpatient
      clinic. Significant correlations were noted with both the Corning Glytrac total
      HbA1 assay (r = 0.89) and the Novoclone assay for HbA1c (r = 0.95). Mean within
      assay CV was 1.6% and 3.0% at HbA1c of 5.4% and 13.0%, respectively, while
      between-assay CVs were 4.2% and 3.8%. These results are as good as our routine
      laboratory method based on the Corning HbA1 assay. Locally derived reference
      population data for HbA1c were produced and patients were assigned to categories
      of good, acceptable, and poor glycaemic control using conventional
      recommendations for Type 2 diabetes. There was poor agreement between the
      methods, with only 22% of patients achieving good/acceptable control using the
      DCA 2000, while 46% of patients had an HbA1 in this range. It appears that the
      convention for derivation of control limits for HbA1 does not hold for this HbA1c
      assay.

PMID- 8306597
TI  - Alternative medicine: potential dangers for the diabetic foot.
AB  - Two patients with non-insulin-dependent diabetes mellitus and previously
      undiagnosed peripheral neuropathy consulted separate practitioners in alternative
      medicine with symptoms of painful cold feet. They both received the traditional
      Chinese therapy of moxibustion and subsequently developed painless ulceration at
      the sites of treatment on the feet and legs. These cases re-emphasize the dangers
      of trauma to the neuropathic limb in patients with diabetes.

PMID- 8306598
TI  - Education and employment for young people with diabetes.
AB  - Educational achievements and employment experiences were examined using a postal
      questionnaire in a random sample of diabetic clinic attenders and non-diabetic
      control subjects aged 16-21 years, selected from 13 different centres in Great
      Britain. A response rate of 63% and 42% for diabetic and control subjects,
      respectively, was obtained. The diabetic group experienced a significantly
      greater number of health difficulties and problems at school (compared with their
      control group (21% vs 11%, p = 0.01) and there was a significant difference in
      perceived useful careers advice obtained at school for the two groups (5% vs 59%,
      p < 0.0001, diabetic and control groups, respectively). There was no difference
      in the number of General Certificates of Secondary Education (GCSEs) and Advanced
      (A) level qualifications obtained between the two groups. Of the young people who
      had left school, diabetic adolescents were significantly more likely to report
      having lost their jobs than their non-diabetic counterparts (19% vs 6%, p =
      0.002). The diabetic group were also more likely to report that they were unable
      to do the job they wanted compared with the non-diabetic group (28% vs 16%, p =
      0.005) and were more likely to report shift work problems (41% vs 12%, p = 0.04).
      With the increasing rate of unemployment it is important that youngsters with
      diabetes obtain specific diabetes-orientated vocational guidance in order to plan
      their careers and provision should be made for this in educational
      establishments.

PMID- 8306599
TI  - Consensus guidelines for the management of insulin-dependent (type 1) diabetes.
      European IDDM Policy Group 1993.

PMID- 8306601
TI  - Effect of adding diamond particles on the fracture toughness of apatite ceramics.
AB  - Composite ceramics dispersed through diamond particles with hydroxyapatite as a
      matrix were prepared by firing at 1250 degrees C under reduced pressure or normal
      atmosphere. The fracture toughness and physical properties of sintered composite
      ceramics were examined to determine methods of strengthening hydroxyapatite
      ceramics. The diamond crystal in composite ceramics was transformed to graphite
      by firing and the fracture toughness of hydroxyapatite ceramics increased with
      diamond addition. At 10 wt% diamond, the maximum value for fracture toughness was
      obtained, and the further addition of diamond particles over 10 wt% caused
      fracture toughness to decrease. Such increases in fracture toughness were
      considered the result of microcracking which occurred during the transformation
      from diamond to graphite.

PMID- 8306600
TI  - The application of fluorinated aromatic dimethacrylates to experimental light
      cured radiopaque composite resin, containing barium-borosilicate glass filler--a
      progress in nonwaterdegradable properties.
AB  - This study investigated the durability, especially the nonwaterdegradable
      qualities, of experimental light-cured composite resin containing barium
      borosilicate glass filler. For this purpose, Bis-GMA, a typical component of base
      monomer in conventional composite resin, was replaced by Bis-GMA-F which is water
      repellent. After over 20,000 thermal cycles, the composite resin containing Bis
      GMA retained only 60 approximately 70% of its initial compressive, diametral
      tensile, flexural strength and flexural elastic modulus. However, the
      experimental composite resin containing Bis-GMA-F as a resin matrix showed no
      loss of compressive, diametral tensile strength or flexural elastic modulus,
      although flexural strength showed some deterioration. It was considered that the
      difference between Bis-GMA-F and Bis-GMA, as resin matrix, caused variation in
      the characteristics of water sorption.

PMID- 8306602
TI  - Characterization of enamel and dentin surfaces after removal of temporary cement-
      study on removal of temporary cement.
AB  - Enamel and dentin surfaces of bovine teeth were characterized after mechanical
      and chemical removal of temporary cements. The surfaces were examined by scanning
      electron microscopy and X-ray microanalysis. Contact angles of distilled water
      were measured to monitor surface wettability. Mechanical removal with a dental
      probe did not completely remove all of the temporary cement from both enamel and
      dentin surfaces. These surfaces usually produced contact angles of distilled
      water greater than that on polished surfaces. Etching with thirty-seven percent
      phosphoric acid effectively removed the temporary cement that remained on enamel
      surfaces after mechanical removal but the etchant was not effective on dentin
      surfaces. Acid etching after mechanical removal of cement significantly decreased
      the contact angles of distilled water on enamel surfaces but the etchant only
      slightly improved contact angles of distilled water on dentin surfaces.

PMID- 8306603
TI  - A basic study of a new adhesive lining cement applied emulsion of hydrophobic
      polymer.
AB  - To diminish the effect of water on the adhesive durability of lining cement, an
      experimental lining cement using a hydrophobic polymer as the cement liquid was
      studied. The polymers were styrene-butadien-alkyl acrylate copolymer (SBA
      copolymer) and carboxylated styrene-butadien-alkyl acrylate copolymer (CSBA
      copolymer) and were used as aqueous emulsions. The cement powder consisted of
      alkaline silicate and calcium disilicate. The pH values of the immersion water of
      the cement prepared from emulsion of SBA copolymer (SBA cement) was almost the
      same as that of calcium hydroxide cement. The compressive and diametral tensile
      strengths of SBA cement gradually increased over time in water. The bond
      strengths of cement prepared from the CSBA copolymer emulsion containing five
      percent carboxyl groups by weight were superior to those of calcium hydroxide
      cement.

PMID- 8306604
TI  - Adhesiveness of glass ionomer cement containing tannin-fluoride preparation (HY
      agent) to dentin--an evaluation of adding various ratios of HY agent and
      combination with application diammine silver fluoride.
AB  - We bonded a glass ionomer cement (GIC) containing various amounts of incorporated
      tannin-fluoride preparation (HY agent) to bovine dentin and investigated the
      effect of the ratio of incorporated preparations and the changes in bond strength
      over time. HY agent was incorporated into the powder at 0% (HY0), 1.5% (HY1.5),
      5.0% (HY5), and 10.0% (HY10) by weight. The shear bond strength and percent of
      the cohesive failure were measured. Similar tests were performed on samples where
      diammine silver fluoride was applied to the dentin prior to placing the cement.
      It was found that the bond strength on the first day was increased by
      incorporating 1.5% of the HY agent in the GIC. The combined use of diammine
      silver fluoride increased the bond strength of the GIC.

PMID- 8306605
TI  - Prediction of the service life of dental porcelains by the measurements of post
      indentation slow crack growth.
AB  - Statistical fatigue life for body dental porcelains, cooled in a furnace and in
      air, was predicted from measurements of post-indentation slow growth of radial
      cracks in water and in air. Cracks were induced in the surfaces of porcelain
      discs by a Vickers indenter at an applied load of 9.8 N. Crack lengths were
      measured at various times over a period of 5 months to calculate the stress
      corrosion susceptibility coefficient, n. Lifetime under service stress was
      estimated from the measured value of n. The ratios of service stress to fracture
      strength were calculated as 0.47 and 0.69, respectively, for glassy and
      feldspathic porcelains which were cooled in a furnace and aged in water. The
      corresponding ratios for tempered (cooled in air) specimens were 0.58 and 0.67,
      respectively. These were estimated values when service life exceeds 10 years. The
      results suggest that the air cooling process can effectively increase the service
      life of glassy porcelains, but, for feldspathic porcelain it is less effective.

PMID- 8306606
TI  - Direct observation of in vivo wear of composite resins.
AB  - This study developed a simple method for in vivo evaluation of wear on composite
      resins and examined the role of filler particles in this process. Experimental
      light-cured composite resins with two different filler systems were prepared: (1)
      81 wt% fine quartz filler (Conventional type) and (2) 73 wt% organic filler
      (Microfilled type). The resin monomer consisted of 50 wt% Bis-GMA and 50 wt%
      TEGMA. These materials were placed in cylindrical cavities 2 mm in diameter
      located in the OCA (occlusal contact area) or the CFA (contact free area) in Au
      Pd crowns, temporarily set in a volunteer's mouth. The crowns were removed at
      monthly intervals for longitudinal SEM observation. Results showed that the newly
      developed method was useful for observing the in vivo wear-patterns of composite
      resins. The two experimental composite resins with different filler systems
      showed quite different wear-patterns.

PMID- 8306607
TI  - Hardness and fracture toughness of commercial core composite resins.
AB  - One important mechanical property of core composite resins is fracture toughness,
      KIC, which expresses serviceability in the oral cavity, such as the resistance to
      marginal fracture. KIC values of eight commercial core composite resins were
      examined by the single-edge notched-beam (S.E.N.B.) method. Two composites
      containing about 80 wt% Si3N4 fillers exhibited both the highest KIC value of
      around 2.0 MN.m-3/2 and the highest hardness value. The other six composites
      containing 66 to 86 wt% SiO2-based fillers had KIC values of around 1.2 to 2.0
      MN.m-3/2, and there was a tendency toward higher KIC values as hardness
      increased. It was speculated that the clinical acceptability of core composite
      resins could be broadened, if dental clinicians selected composites with higher
      KIC values.

PMID- 8306608
TI  - Further NMR-spectroscopic studies of interaction of phospholipid liposomes with
      methacryloyloxydecyl dihydrogen phosphate (MDP) in dental adhesives.
AB  - To determine how MDP interacts with liposomes, the chemical shifts of
      dipalmitoylphosphatidylcholine (DPPC)/MDP and dilauroylphosphatidylethanolamine
      (DLEA)/cholesterol (CS)/MDP liposomes were studied by NMR spectroscopy using a
      D2O buffer solution at pH 7.0 as a model for biological membranes. Proton
      chemical shifts of MDP enhanced shielding in DPPC liposomes together with an
      increase in the mobility of DPPC. However, MDP signals were not observed in
      DLEA/CS liposomes due to saturation. It is known that an ionized chemical does
      not lead to increased permeability of cell membranes composed of a lipid bilayer.
      However, MDP, which is ionized at pH 7.0, had a large interaction with the
      liposome systems. This appeared to arise from hydrophobic interaction between
      deca methylene groups of MDP and acyl chains of phospholipid.

PMID- 8306609
TI  - Appraisal of dental anxiety and fear questionnaires: a review.
AB  - This article reviews and assesses six dental anxiety and fear questionnaires. The
      construct aimed at by the questionnaires, the data collected, their reliability,
      validity and normative scores are considered. Some attention is given to the
      correlations between the questionnaires, their ambiguity, the presence of
      manuals, and whether the questionnaires tap the three segments distinguishable on
      theoretical ground in dental anxiety/fear. All questionnaires are open to
      criticism. In the final assessment Kleinknecht's Dental Fear Survey is preferred
      to Corah's Dental Anxiety Scale. The latter, however, appears useful in getting a
      quick impression of anxiety and in evaluative studies. Three recently developed
      questionnaires, Stouthard's Dental Anxiety Inventory, Weiner's Fear Questionnaire
      and Morin's Adolescents' Fear of Dental Treatment Cognitive Inventory are
      considered promising, but for the last two instruments more data, in particular
      with regard to their validity, are needed. It is concluded that in dental anxiety
      research more than one questionnaire should be used and that it may be worthwhile
      to include other, non-anxiety questionnaires as well.

PMID- 8306610
TI  - Sociodental approach to the identification of dental treatment-need groups.
AB  - The aim of this study was to propose a method that could be used to distinguish
      significantly different dental treatment-need groups, to assist in planning more
      appropriate preventive dental health programmes than are now generally available.
      This involved the use of alternative new measures of dental status in conjunction
      with an indicator of people's potential, or "propensity" to adopt appropriate
      dental self-care measures. One important finding, based on a detailed
      questionnaire and dental examination of a sample population, is that substantial
      groups have relatively low or medium levels of dental status even though they
      possess relatively high propensity for self-care measures. A cross-classification
      of oral health status with the propensity indicator is used to define different
      treatment-need groups. Significant differences among these groups emerge in
      relation to various social indicators like age group, gender, region and dental
      history, and in relation to preventive dental health measures such as dental
      attendance and efficacy of teeth cleaning. The methodology proposed for
      identifying such different treatment-need groups could be valuable in devising
      effective community dental health strategies.

PMID- 8306611
TI  - Validity of CPITN's assumptions of hierarchical occurrence of periodontal
      conditions in a Kenyan population aged 15-65 years.
AB  - In order to study the validity of the hierarchical principle of the CPITN we used
      data originating in a cross-sectional study of periodontal disease in a random
      sample comprising 1131 Kenyans aged 15-65 yr to determine, for each tooth present
      in each individual, the absence or presence of gingival bleeding, of dental
      calculus, of a pocket of 4-5 mm or a pocket of 6+ mm, such that each tooth had a
      separate recording for bleeding, calculus, pocket 4-5 mm and pocket 6+ mm.
      According to the hierarchical principle of CPITN a tooth with pockets as the most
      severe finding is assumed positive also for calculus and bleeding, and a tooth
      with calculus as the most severe finding is assumed positive also for bleeding.
      Our analysis showed that calculus as the most severe finding of a tooth
      overestimates the occurrence of bleeding by up to 18%, depending on age of the
      individuals and the set of teeth examined. Pockets as the most severe finding in
      a tooth overestimates the occurrence of bleeding by up to 13%, and overestimates
      calculus by up to 54%, most pronounced in the younger age groups. The effect of
      these overestimations on prevalence and severity estimates was the most
      pronounced for the severity measures, particularly regarding the severity of
      bleeding, whereas prevalence estimates remained relatively unaffected.
      Undoubtedly, this result should be seen in the light of a very high prevalence
      and severity of both bleeding and calculus in this population.

PMID- 8306612
TI  - Influence of CPITN partial recordings on estimates of prevalence and severity of
      various periodontal conditions in adults.
AB  - This study compares the results of a full mouth examination with the results of
      examining only the CPITN selection of 10 index teeth 17/16, 11, 26/27, 47/46, 31
      and 36/37 for estimates of prevalence and severity of the conditions assessed
      with the CPITN, i.e. gingival bleeding, dental calculus, pockets 4-5 mm deep and
      pockets 6+ mm deep. The mean number of sextants recorded with bleeding or with
      calculus was generally overestimated when examinations were based on the CPITN
      selection of index teeth, whereas the mean number of sextants with pockets,
      whether moderate or deep, were generally underestimated. Similarly, the
      prevalence of pockets, whether moderate or deep, was underestimated in virtually
      all age groups while the prevalence of calculus was overestimated in all age
      groups and the prevalence of bleeding was overestimated among persons below 30 yr
      of age. We conclude that the partial recording approach of the CPITN methodology
      is reasonably well suited for identifying persons who are relatively healthy
      according to the hierarchy of the CPITN parameters. There is, however, a
      considerable risk that persons presenting with the more severe conditions, i.e.
      pockets, will be overlooked if only partial recordings are performed.

PMID- 8306613
TI  - Aesthetic concerns of children and parents in relation to different
      classifications of the Tooth Surface Index of Fluorosis.
AB  - Increasing prevalence of dental fluorosis for children both from fluoridated and
      non-fluoridated communities are now well documented. Along with recent studies
      purporting possible adverse health effects from fluorides, this proven public
      health intervention is again being challenged. This study was undertaken to
      determine the prevalence of dental fluorosis for children from fluoridated and
      non-fluoridated areas in British Columbia. In addition, children and parents were
      provided with an opportunity to express concerns about the aesthetics of the
      child's anterior teeth. Children from representative schools in two communities
      were surveyed using the Tooth Surface Index of Fluorosis (TSIF). Questionnaires
      were sent home to parents to detail their child's use of various fluoride
      preventive practices and residence histories. Completed questionnaires were
      returned and exams were performed on 1131 children. Of those examined, 60% had
      dental fluorosis on at least two tooth surfaces, only 8% had scores ranging from
      "2" to "6", and 52% were classified with a score of "1". Parental and child
      ratings on the aesthetics or color of the child's teeth suggests that there are
      few children with aesthetic problems in the TSIF category of "1". While concerns
      of parents were more common, the actual source of those concerns was not assessed
      in the questionnaire. Not unexpectedly, children with fluorosis on anterior teeth
      ranging between TSIF scores of "2" to "6" appear to have increased concerns about
      tooth color. Data from children with confirmed residence histories from
      fluoridated communities suggest that the occurrence of aesthetic problems in
      these children is rare.

PMID- 8306614
TI  - Prediction of caries incidence in schoolchildren living in a high and a low
      fluoride area.
AB  - A salivary mutans streptococci test and past caries experience were used as
      predictors for caries increment in a 3-yr study comprising 655 12-yr-old
      schoolchildren from two areas with contrasting levels of fluoride in the drinking
      water. The mean caries (DMFS) increment was similar in both groups during the
      study period, but a significantly (P < 0.05) higher incidence of approximal
      enamel lesions was registered in children from the high fluoride area. In both
      groups, a statistically significant (P < 0.05-0.001) positive relationship
      between salivary mutans streptococci score and/or past caries experience at
      baseline on one hand and caries increment during the study period on the other
      was established. The past caries experience was the most powerful predictor of
      caries risk in both the low fluoride and the high fluoride area. The sum of the
      sensitivity and specificity was somewhat higher in the low fluoride area (138%)
      compared to the high fluoride area (123%). The salivary bacterial enumeration
      used alone or in combination with past caries experience as well as past
      approximal caries experience were less useful as predictors in both groups. The
      present findings indicate that the natural fluoride exposure has a limited
      influence on caries risk assessment and the caries predictive ability of the
      salivary bacterial test and past caries in populations with a low level of
      disease.

PMID- 8306615
TI  - Prevalence and characteristics of areca nut chewers among junior high school
      students in Changhua county, Taiwan.
AB  - Some studies indicate that betel quid and its ingredients chewing can produce
      cell mutagenicity and tumorigenicity. In Taiwan studies, betel quid chewing is
      the main cause of submucous fibrosis and oral cancer. Understanding the
      distribution and characteristics of the areca nut chewing population is one of
      the first steps in the effort to prevent these oral diseases. A stratified
      cluster random sample of 2442 junior high school students in Changhua county,
      Taiwan, were surveyed for the habit of areca nut chewing. Significantly more male
      students chewed areca nut than female students (9.2% vs 0.9%). The proportion of
      students who were chewing areca nuts increased with increasing (seventh to ninth)
      grades. Areca nut was used by junior high school students at a higher rate in
      village (rural) areas as compared to town (semi-urban) and city (urban) areas
      (6.4%, 3.7% and 3.0%, respectively). More students in the ordinary achievement
      classes were chewing areca nuts than those in the high achievement classes (8.4%
      vs 1.6%). Areca nut chewing students tended to have users in their families.
      Cigarette smoking and alcohol drinking were positively associated with areca nut
      chewing. More than half (53.6%) of the areca nut chewing students first
      experimented with this habit with a family member, most often the father or
      grandfather.

PMID- 8306616
TI  - Composite indicators of dental health: functioning teeth and the number of sound
      equivalent teeth (T-Health).
AB  - This study investigated whether two new composite dental indicators--"the number
      of functioning teeth" and "the number of sound-equivalent teeth"--are more
      efficient than the conventional DMFT index in revealing the social and
      behavioural factors which are significantly related to oral health status. The
      arbitrary set of weights given to the T-Health indicator was also evaluated. The
      number of functioning teeth was defined as the aggregate of filled (otherwise
      sound) and sound teeth. The T-Health was defined as a weighted average of sound
      teeth, filled (otherwise sound) teeth and teeth with some decay, the weights
      intended in principle to represent the relative amounts of sound tissue in these
      three categories of teeth. An arbitrary set of weights was used: 4, 2, and 1 for
      sound, filled, and decayed teeth, respectively. 164 families (father, mother and
      at least one 13-yr-old child) from Belo Horizonte, Brazil, were randomly selected
      from 13-yr-old children from private and state schools. The parents' ages ranged
      from 35 to 44 yr. Socio-economic status, area of residence, level of education,
      family income, sugar consumption, toothbrushing frequency and type of dental
      attendance were the social and behavioural oral health risk-factors considered in
      this study. The results indicated that the two new dental indicators are more
      sensitive to the influence of social and behavioural factors, such as those
      investigated here, than is the traditional DMFT index. A different set of weights
      (4, 1, and 1 for sound, filled, and decayed) was suggested for the construction
      of the T-Health.

PMID- 8306617
TI  - Reasons for tooth extraction in the western states of Germany.
AB  - The purpose of this study was to collect information on the main causes of tooth
      loss in the western states of Germany as perceived by dentists and their
      patients. Sixty-eight dentists, out of 80 that were selected with a systematic
      random method for an epidemiological study in the western states of Germany,
      recorded their reason for tooth extraction. Included in the study were only
      extractions of permanent teeth during a period of 2 weeks (March 1990), up to a
      maximum of 20 patients per dentist. Of 926 returned questionnaires, 882 could be
      evaluated. In all 1215 teeth in 882 patients were extracted. The extraction of
      third molars was included as a reason, when caries, periodontal reasons and
      others were not indicated. Caries was the reason given for 20.7% of all
      extractions; periodontal diseases for 27.3%; caries and periodontal reasons for
      18.7%; third molars for 14.7%; prosthetic reasons for 11.2%; orthodontic reasons
      for 4.1%; trauma for 0.4% and others for 2.9%. While caries is a major reason in
      all age groups, periodontal diseases and the combination of caries and
      periodontal reasons are more frequent than all other reasons for the age groups
      beyond 40 or 45 yr, respectively. The third molar was the most often extracted
      tooth. The patients were asked for their main reason for tooth extraction. For
      the patients, pain was the major reason for extraction (47.2%). According to the
      participating dentists periodontal disease is the most frequent cause of tooth
      extraction for people over 40 yr of age, while for those below 40 yr of age,
      caries and third molar extractions are the most frequent reasons.

PMID- 8306619
TI  - Mouth dryness as reported by older Floridians.
AB  - Thirty-nine percent of 600 community-dwelling older Floridians (mean age of 78
      yr) reported having mouth dryness. Seventy-nine percent of respondents reported
      at least one medical condition, 57% were taking at least one prescribed or over
      the-counter medication, and 33% were taking at least one potentially xerostomic
      medication. Reported mouth dryness was highly associated with the number of
      potentially xerostomic medications. After stratification by medication usage,
      age, diabetes, arthritis, perceived medical health, and dependence in physical
      functioning were significantly associated with mouth dryness. Persons with dry
      mouth were also more likely to have reported dental symptoms, signs of dental
      disease, sensory changes, and other oral symptoms. Ten percent of those who
      reported mouth dryness also said that their mouths felt dry when eating a meal,
      10% said that they had difficulties swallowing foods, and 15% of persons with dry
      mouth also said that the amount of saliva in their mouths was too little. Sixty
      five percent of persons with dry mouth reported doing one or more dryness-related
      behaviors. These results suggest that the prevalence of xerostomia was high, and
      the impact of dry mouth on individuals' daily behaviors was significant.

PMID- 8306618
TI  - Attitudinal and behavioral characteristics of older Floridians with tooth loss.
AB  - In this cross-sectional study of Floridians aged 65 yr or older, 600 persons were
      interviewed to identify the characteristics of individuals who survived into old
      age with an intact or nearly intact dentition. Persons with total or partial
      tooth loss reported less frequent dental care, less ability to pay dental care
      fees, less frequent dental hygiene, and were more likely to have been smokers or
      diabetic. Persons with tooth loss also had less positive attitudes toward
      dentists and dental care. These cross-sectional findings are consistent with
      tooth loss being the result of disease-, behavior-, and attitude-related causes,
      and/or their interactions. Tobacco use, diabetes, and infrequent oral hygiene and
      dental care may increase risk for dental disease; decreased ability to pay for
      dental treatment may impair utilization of non-extraction treatment options, and
      negative attitudes toward dental treatment may influence the desire for non
      extraction treatment options. Research targeted toward modifying attitudes toward
      dental treatment may be useful in preventing or delaying tooth loss, and
      measurement of attitudes may be a useful way to identify individuals at the
      greatest risk for tooth loss for intervention studies.

PMID- 8306620
TI  - Prevalence of dental caries among the schoolchildren of Andorra.

PMID- 8306621
TI  - An aggregation of pro and con evidence for medical decision support systems.
AB  - One promising way to increase the classification accuracy of medical decision
      support systems is to implement heuristic combinations of pattern recognition and
      artificial intelligence tools. A parallel between "cognition" model and
      differential diagnostic task is sketched accentuating the aggregation of
      activating and restraining inputs and corresponding PRO and CON evidence in
      medicine. On the basis of this paradigm a trainable model of a fuzzy neuron is
      proposed which resembles some elements from the physician's decision process. An
      example from aviation medicine is presented which demonstrates the enhanced
      performance.

PMID- 8306622
TI  - A nonlinear perspective in understanding the neurodynamics of EEG.
AB  - The developments in nonlinear dynamics and the theory of chaos have considerably
      altered our perception and analysis of many complex systems, including the brain.
      This paper reviews the physical and dynamical aspect of brain's electrical
      activity from this new perspective and indicates possible future directions. The
      importance of emerging trends of nonlinear dynamics and chaos to neurobiology has
      been discussed in the context of various states of consciousness and behaviour.
      In the past, EEG analysis has been confined to descriptive stochastic statistics
      and any understanding of the transitional process of brain activities was either
      nonexistent or not amenable for investigation. With the developments in nonlinear
      dynamics, the chaotic dynamical parameters and trajectory behaviour will find
      their use as feature detection techniques in EEG. Furthermore, nonlinear dynamics
      provides a model for EEG generation and temporal prediction which will help in
      determining the nature of neuronal processes governing various states of brain
      activity. The formalism of globally coupled dynamic systems will find
      applications in modelling the transitional states of EEG.

PMID- 8306623
TI  - A computer model for analysis of fluid resuscitation.
AB  - Injuries involving massive blood loss, such as burns, combat wounds, and injuries
      resulting from car accidents, require fluid resuscitation. The risk involved in
      fluid therapy is overloading of the circulation, resulting in pulmonary edema
      which can lead to death. The risk of pulmonary edema may be eliminated by proper
      determination of maximal infusion volume and rate. Reabsorption of fluid from the
      extravascular compartment and infusion of fluid following blood loss results in
      reduction of the hematocrit. This is accompanied by an increase in the heart's
      preload and afterload. Coronary driving pressure and flow increase due to
      increased volume. However, because of the reduced hematocrit this increase in
      coronary flow may not be sufficient to compensate the myocardium, in terms of
      oxygen supply, for the increase in oxygen consumption. A model of the
      cardiovascular system, including an extravascular compartment, was designed to
      analyze the effects of fluid infusion on hemodynamic variables, cardiac oxygen
      balance, and the redistribution of fluid between intravascular and extravascular
      compartments. The results indicate that edema is not the only possible adverse
      effect of overloading the cardiovascular system with fluid. The simulation
      demonstrated that in certain cases the heart's oxygen balance can become
      negative. Limiting the rate of infusion can reduce this risk.

PMID- 8306624
TI  - An algorithm accounting for plating efficiency in estimating spontaneous mutation
      rates.
AB  - An algorithm is described for calculating the probability distribution of the
      number of mutant colonies arising in a Luria-Delbruck fluctuation experiment
      subject to a plating efficiency of less than 100%. A table is constructed to
      facilitate the estimation of spontaneous mutation rates taking into account the
      plating efficiency.

PMID- 8306625
TI  - RAMHA: a PC-based Monte-Carlo simulation of random saturation mutagenesis.
AB  - Random mutagenesis is a powerful tool in protein structure-function analyses. One
      approach to random mutagenesis is the de novo synthesis of polypeptide-encoding
      oligodeoxy-nucleotides using doped nucleoside phosphoramidites. A Turbo PASCAL
      program, RAMHA, is described for modeling such mutagenesis. Upon entering the
      target sequence and the desired level of nucleotide contamination, RAMHA performs
      a Monte Carlo simulation of the mutagenesis, compiling statistics on the
      similarity of resultant mutant polypeptides to the wild-type sequence, the
      frequency of premature open-reading frame terminations, and other relevant
      outcomes. Simulated mutagenesis of two DNA targets has led to the development of
      two different strategies to avoid the random introduction of stop codons within
      mutagenized gene segments.

PMID- 8306626
TI  - An efficient method for computer-aided dosage form design.
AB  - It is desirable to have slow-release dosage form to be taken once daily, or at
      most twice daily, as compared to three or four times in a single day. However,
      the existing computer-aided dosage form design method requires a large amount of
      computer time when applied to nonlinear disposition drugs. This large commitment
      of computer time makes it inconvenient to study the feasibility for prolonged
      release products containing such drugs. Instead of evaluating all possible
      combinations of the amount of dose and release rates that produce acceptable
      steady-state plasma concentrations, only the contour of the dose-release rate
      domain needs to be determined. An image boundary tracking method has been used to
      determine such contours. When combined with several modifications of the
      numerical solution process, the acceptable dose and release rate constants can be
      determined efficiently. When this modified boundary tracking method was applied
      to phenytoin, which exhibits nonlinear disposition, the required computer time
      was reduced to about 5% of the previous method, making the dosage form
      feasibility assessment practical.

PMID- 8306627
TI  - Application of form features in digital cell analysis of non-Hodgkin's lymphomas.
AB  - The form of a biological cell nucleus can be characterized by the well-known
      circularity factor, which is derived from the area of an object and its
      circumference. More sophisticated form features are introduced, which are
      calculated from the curvature of an object ("bending energy") or from invariant
      moments. To investigate the sensitivity of the various form features on
      controlled changes of form and the behaviour under rotation and scaling,
      algebraic curves similar to the form of real nucleus profiles are generated.
      Analysis of the shape characteristics of biological cells requires an extraction
      of the boundaries of the nuclei. This was performed by an edge detection
      algorithm using eight gradient masks followed by a contour tracing procedure with
      feedback. The suitability of the introduced form features for classification of
      different nucleus profiles of non-Hodgkin's lymphomas (NHL) was tested using a
      Bayes classifier.

PMID- 8306628
TI  - Adaptive cancellation of the respiratory artifact in surface recording of small
      intestinal electrical activity.
AB  - In the human small intestine there is omnipresent electrical activity with a
      frequency of 0.15-0.2 Hz. The electrical activity of the small intestine can be
      measured by surface electrodes placed on the abdominal skin. The most annoying
      problem in the surface electrical recording is the respiratory artifact which is
      not discernible from the small intestinal signal. The frequency of the
      respiration is about 0.2-0.4 Hz, which is very close to that of small intestinal
      activity, making the use of the conventional bandpass filtering impractical. In
      this paper a selective frequency domain adaptive filter was proposed for the
      cancellation of the respiratory artifact. The basic principle of the selective
      frequency domain adaptive filter is that only selected filter weights are adapted
      based on the frequency characteristics of the respiratory artifact. Therefore, a
      substantial reduction of computation is achieved. A series of computer
      simulations was conducted for the optimization of the system parameters and for
      the investigation of the system performance. It was demonstrated in this paper
      that the selective frequency domain adaptive filter is as effective as, but more
      efficient than, the conventional frequency domain adaptive filter. The adaptive
      system for the cancellation of the respiratory artifact based on the selective
      frequency domain adaptive filter is very efficient in computation, has a fast
      convergence (about 100 adaptations), substantial reduction of the respiratory
      artifact and little effect (or distortion) on the small intestinal electrical
      signal.

PMID- 8306629
TI  - Efficiency of searchpatterns.
AB  - Search theory deals with the efficiency of covering searchpatterns; a classical
      example is systematic row search with sweep spacing dependent upon window size.
      Human visual search is a function of contrast and size of the targets and of
      effective visual lobe size, this latter influenced by clutter and foveal load.
      Human searchpatterns often are optimal covers. Experimental results presented in
      this paper demonstrate that this is true for instrumental search with display
      windows controlled by human subjects and quantified with a formula for
      efficiency. Visual searchpatterns using free eye movements often develop complex
      irregular sequential searchpatterns.

PMID- 8306630
TI  - Luria-Delbruck fluctuation analysis: estimating the Poisson parameter in a
      compound Poisson distribution.
AB  - Estimating the mutation rate from a Luria-Delbruck fluctuation experiment
      involves estimating the Poisson parameter in a compound Poisson distribution. The
      efficiency with which this can be estimated depends on how well the other random
      factors have been characterized. The assumption that cell growth can be
      represented as a stochastic pure birth or Yule process is biologically
      unrealistic but contributes little to the bias and variance of a maximum
      likelihood estimator of the mutation rate.

PMID- 8306631
TI  - Circulating IGF-I in plasma of growing male and female turkeys of medium and
      heavy weight lines.
AB  - Plasma concentrations of insulin-like growth factor-I (IGF-I) were determined in
      male and female turkeys from a medium weight (RBC2) and a related heavy weight
      line (F) from 1 to 28 wks of age. At hatch, the concentrations of IGF-I were
      relatively low and not different between lines or sexes. During the neonatal
      period (1 to 7 wks), the concentrations of IGF-I increased and were higher in the
      faster growing F line and in males. During the juvenile period (8 to 15 wks) the
      concentrations of IGF-I were higher in males but not different between lines.
      During the preadolescent period (16 to 21 wks), the concentrations of IGF-I were
      higher in males but was not different between lines in males while the females of
      the RBC2 line had higher concentrations than females of the F line. During the
      adolescent period (22 to 28 wks) the concentrations of IGF-I were higher in males
      but was not different between lines in males while the females of the RBC2 line
      had higher concentrations than females of the F line. A phenotypic correlation
      (+.25) between plasma IGF-I and growth rate was present after statistical
      absorption of model effects during the neonatal period but not at the later ages.
      We conclude that IGF-I concentration was positively correlated with growth rate
      during the neonatal period, but that this relationship changed during the
      preadolescent and adolescent periods so that IGF-I concentrations were not
      related to growth rate in males but were negatively related to growth rate in
      females.

PMID- 8306632
TI  - Pancreatic insulin secretory response and insulin action in heat-exposed sheep
      given a concentrate or roughage diet.
AB  - The effects of heat exposure and type of diet on the insulin secretory response
      to glucose and glucose disposal in response to insulin action in female sheep
      were investigated employing hyperglycemic and euglycemic clamp techniques.
      Animals were divided into concentrate and roughage diet groups, and were
      maintained at the same intake levels of metabolizable energy and crude protein in
      both diets. Each diet group was subjected to either thermoneutral (20 degrees C,
      70% RH) or hot (30 degrees C, 70% RH) environment, followed by glucose clamp
      experiments. Heat-exposed sheep showed significant increases in respiration rates
      (P < .001) and rectal temperature (P < .05). Plasma glucose concentrations in the
      basal conditions were lower (P < .01) in the hot environment than in the
      thermoneutral environment, but there was no significant difference in basal
      levels of plasma insulin between the environmental treatments. In the
      hyperglycemic clamp experiment, mean plasma insulin increments increased (P <
      .05) during the heat exposure period across diet treatments. The ratio of mean
      plasma insulin increment to glucose infusion rate tended to be higher (P < .07)
      in the hot environment than in the thermoneutral environment, but diet treatment
      did not affect the ratio of mean plasma insulin increment to glucose infusion
      rate. The euglycemic clamp technique showed that glucose infusion rates remained
      unchanged among treatments. Insulin secretion response to glucose could be
      stimulated in the hot environment.

PMID- 8306633
TI  - Production of immunoactive inhibin by bovine granulosa cells in serum-free
      culture: effects of exogenous steroids and FSH.
AB  - Granulosa cells from pooled bovine follicles were cultured under chemically
      defined (serum-free) conditions to study the effects of exogenous steroids and
      FSH on production of immunoactive (ia) inhibin, oestradiol and progesterone.
      Levels of ia-inhibin in media samples and cell lysates were measured by
      radioimmunoassay (RIA) using an antiserum raised against a synthetic fragment of
      human inhibin alpha-subunit [hI alpha (1-32)]. Cells secreted measurable amounts
      of ia-inhibin, oestradiol and progesterone for at least 7 d of culture, although
      intracellular levels of inhibin were very low, indicating that newly-synthesized
      ia-inhibin is rapidly released from the cells. Treatment with androstenedione
      (0.2 mumol/l) or testosterone (0.2 mumol/l) increased ia-inhibin secretion
      markedly; levels on Day 5 of culture were approximately 6-fold (P < 0.005) higher
      than control values. In contrast, treatment with the non-aromatizable androgen
      dihydrotestosterone (DHT; 0.2 mumol/l) resulted in only a one- to two-fold
      increase (P < 0.05) over control values (Day 5). Addition of exogenous oestradiol
      (8 nmol/l) markedly increased ia-inhibin secretion (8-9 fold on Day 5; P < 0.05)
      compared with basal levels, whereas progesterone had no effect. Secretion of
      oestradiol, undetectable in the absence of exogenous androgens, rose daily in the
      presence of either androstenedione or testosterone, levels rising approximately 6
      fold and 9-fold respectively over a 4-d treatment period. Progesterone secretion
      increased approximately 2-fold over the culture period and was unaffected by any
      steroid treatment. Treatment with ovine FSH (10ng/ml) alone stimulated secretion
      of progesterone over basal levels (3-fold higher on Day 6; P < 0.005), but did
      not affect output of either ia-inhibin or oestradiol. However, exposure to FSH in
      the presence of androstenedione not only promoted a further 4-fold increase in
      progesterone output but also led to a dose-dependent suppression of both ia
      inhibin (approximately 90% lower on Day 6; P < 0.001) and oestradiol
      (approximately 80% lower on Day 6; P < 0.001) secretion compared to cells treated
      with androstenedione alone. These observations indicate that the secretion of ia
      inhibin by bovine granulosa cells in culture is positively regulated by
      oestradiol, implying an autocrine/paracrine role for this hormone in control of
      ovarian inhibin production. The ability of aromatizable androgens to stimulate
      secretion of inhibin, coupled with the inability of the non-aromatizable androgen
      DHT to elicit such an effect, suggests that inhibin output is largely unaffected
      by androgens prior to their conversion to oestradiol.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8306635
TI  - Molecular cloning, sequencing, and characterizing the bovine receptor for
      gonadotropin releasing hormone (GnRH).
AB  - Receptors for gonadotropin releasing hormone (GnRH), located in the cell
      membranes of adeno-hypophysial gonadotropes, mediate the action of GnRH to
      stimulate the secretion of the gonadotropic hormones (LH and FSH). In the present
      studies, we have isolated a GnRH receptor cDNA from bovine pituitary, determined
      its primary structure, and studied the regulation of its gene expression. The
      cDNA is composed of 1326 nucleotides and encodes a protein containing 328 amino
      acids. The GnRH receptor of cattle, like that in humans and mice, is a seven
      transmembrane receptor and has structural characteristics homologous with the
      family of G protein-coupled receptors. It exhibits 91% identity at the amino acid
      level with the human and 86% identity with mouse and rat receptors. Northern blot
      analysis of the RNA from bovine pituitary, probed with 32P-labeled bovine GnRH
      receptor cDNA, revealed the presence of four different transcripts (5.0, 3.5, 2.5
      and 1.5 kb) in the pituitary of which the 5.0 kb form was most abundant. Using
      the reverse transcriptase/PCR technique, we detected expression of GnRH receptor
      mRNA in the pituitary but not in any other extrapituitary tissues such as the
      hypothalamus, hippocampus, testis, corpus luteum, ovary (containing follicles),
      myoendometrium, adrenal, kidney, liver and spleen. Higher levels of GnRH receptor
      mRNA were found in the pituitaries of steers than in cohort bulls, suggesting
      regulation of GnRH receptor gene expression by testicular steroids.

PMID- 8306636
TI  - Distinguishing mixed anxiety/depression from anxiety and depressive groups using
      the family history method.
AB  - The relationship between anxiety and depression has long been discussed and
      studied. Although it appears that there are pure forms of these disorders,
      several investigators have suggested that there is a separate combined
      anxiety/depression disorder distinct from either individual disorder. Several
      attempts have been made to investigate this distinction using family history
      methods. This report compares an anxiety/depression group to a depression-only
      group and anxiety-only group in a veteran population (n = 71) using the family
      history method. The depression group was clearly differentiated from the
      anxiety/depression group on the variables of generalized anxiety disorder and
      alcohol abuse. There was also discrimination between the anxiety and
      anxiety/depression groups on the DSM-III-R anxious personality disorder cluster.
      This is the first report in this area of the literature to use standardized
      family history methods that include personality disorder clusters.

PMID- 8306634
TI  - N-methyl-d,l-aspartate modulation of pituitary hormone secretion in the pig: role
      of opioid peptides.
AB  - Sixteen ovariectomized (OVX) mature gilts, averaging 139.6 +/- 3.1 kg body weight
      (BW) were assigned randomly to receive either progesterone (P, 0.85 mg/kg BW, n =
      8), or corn oil vehicle (OIL, n = 8) injections im twice daily for 10 d. On the
      day of experiment, all gilts received either the EAA agonist, N-methyl-d,l
      aspartate (NMA; 10 mg/kg BW, iv) alone or NMA plus the EOP antagonist, naloxone
      (NAL, 1 mg/kg BW, iv), resulting in the following groups of 4 gilts each: OIL
      NMA, OIL-NMA-NAL, P-NMA and P-NMA-NAL. Blood samples were collected via jugular
      cannula every 15 min for 6 hr. All pigs received NMA 5 min following pretreatment
      with either 0.9% saline or NAL 2 hr after blood collection began and a GnRH
      challenge 3 hr after NMA. Administration of NMA suppressed (P < 0.03) LH
      secretion in OIL-NMA gilts and treatment with NAL failed to reverse the
      suppressive effect of NMA on LH secretion in OIL-NMA-NAL gilts. Similar to OIL
      NMA gilts, NMA decreased (P < 0.03) mean serum LH concentrations in P-NMA gilts.
      However, in P-NMA-NAL gilts, serum LH concentrations were not changed following
      treatment. All gilts responded to GnRH with increased (P < 0.01) LH secretion.
      Additionally, administration of NMA increased (P < 0.01) growth hormone (GH) and
      prolactin (PRL) secretion in both OIL-NMA and P-NMA gilts, but this increase in
      GH and PRL secretion was attenuated (P < 0.01) by pretreatment with NAL in OIL
      NMA-NAL and P-NMA-NAL gilts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306637
TI  - Generalized anxiety disorder with early and late onset of anxiety symptoms.
AB  - Some generalized anxiety disorder (GAD) patients experience subclinical or
      clinical levels of anxiety before adulthood, whereas others have a later onset.
      To determine whether patients who experienced subclinical or clinical anxiety in
      the first two decades of life differed from those with a later onset, we reviewed
      the history, ratings on various scales, and psychophysiological recordings
      obtained from 103 GAD patients. Early-onset patients were younger and more likely
      to develop GAD without a precipitating stressful event. With the exception of
      depression in the early-onset group, present-state measures did not differentiate
      the two groups. During childhood, patients in the early-onset group were exposed
      to more domestic disturbances, experienced more childhood fears, and were more
      inhibited and socially maladjusted. As adults, they scored higher on trait
      anxiety and neuroticism, tended to have obsessional traits, were more sensitive
      in interpersonal relationships, and experienced more marital difficulties. These
      findings may be explained by (1) constitutional traits that make early-onset GAD
      patients more vulnerable to stressors; (2) a more disturbed environment during
      childhood that adversely affects personality development; or (3) a more severe
      disorder with an early subclinical onset that also affects personality
      development.

PMID- 8306638
TI  - Causes of death among 936 elderly patients with 'pure' anxiety neurosis in
      Stockholm County, Sweden, and in patients with depressive neurosis or both
      diagnoses.
AB  - The survival probability and distribution of causes of death were estimated among
      all 255 male and 685 female inpatients with "pure" anxiety neurosis in Stockholm
      County between 1969 and 1986 who had survived until 71 years of age. When
      controlling for sex, age, time period, and catchment area, we found three
      determined suicides among the men (v 0.8 expected) and four suicides among the
      women (v 1.1 expected). The shift in the distribution of causes of death was
      significant in women (P = .024). There were 55 heart deaths among the men versus
      46.1 expected. Among 2,331 patients with depressive neurosis and among 1,641
      patients with both anxiety and depressive neuroses, suicides were more common
      than expected in both elderly men and women.

PMID- 8306639
TI  - Diagnostic reliability of the history of hypomania in bipolar II patients and
      patients with major depression.
AB  - Records of patients who had been systematically evaluated at the Center for
      Anxiety and Depression were reviewed. Included in this report are records of
      patients who had a diagnosis of bipolar II or unipolar affective disorder as
      determined by one of the authors and who also underwent a Structured Clinical
      Interview for DSM-III (SCID). A second study was undertaken with L.K.T. observing
      the clinical interview of D.L.D. and both clinicians making a diagnosis for the
      patient. There was reasonable diagnostic agreement between D.L.D. and the SCID
      for diagnosis of bipolar II disorder. Twelve of 34 patients clinically diagnosed
      as bipolar II were diagnosed by the SCID as unipolar. These 12 patients failed to
      demonstrate clinical factors, which could help explain the diagnostic difference
      between SCID and the clinical diagnosis. There was excellent agreement on 34
      patients as to the presence or absence of hypomania, comparing two clinicians.
      The SCID interview underestimates the diagnosis of hypomania, a condition that
      can be diagnosed reliably by clinicians trained to make this diagnosis. This
      finding has some implications for DSM-IV, where there is a proposal for inclusion
      of bipolar II disorder as a parallel entity with bipolar disorder.

PMID- 8306640
TI  - Depression and demoralization: phenomenologic differences and research
      perspectives.
AB  - Demoralization may be viewed as a combination of distress and subjective
      incompetence. The main problem in demoralization is the sense of incompetence
      experienced by the demoralized individual; this sense of incompetence results
      from uncertainty as to the appropriate direction of action. By contrast, the
      major difficulty in endogenomorphic depression is a decreased magnitude of
      motivation even when the appropriate direction of action is known. This
      distinction is important not only because demoralization appears to be a major
      public health problem, but also because subjective incompetence appears to
      influence the course and worsen the prognosis of both nonpsychiatric and
      psychiatric disorders.

PMID- 8306641
TI  - Sociocultural and clinical characteristics of patients with comorbid depressions:
      a comparison of substance abuse and non-substance abuse diagnoses.
AB  - Patients with three varieties of major depression (MD) were compared with respect
      to sociocultural and clinical characteristics. The patients sought psychiatric
      evaluation in an intake setting during a 6-year interval. The groups that were
      compared included MD (sole axis I diagnosis; N = 3,913); MD with a comorbid non
      substance abuse ([MD-nonSA] N = 594); and MD with a comorbid substance abuse ([MD
      SA] N = 690). Prominent demographic differences were found in the three groups,
      with males, lower social class status, younger age, and African American
      ethnicity being more prominent in MD-SA. The four demographic variables, axis I
      status, axis II diagnosis, and axis III diagnosis constituted the independent
      variable in an analysis of variance (ANOVA) main-effects comparison of social
      function (during last year and currently in three areas) and type of depression
      symptoms (somatic and psychological). Of the demographic variables, age and
      social class proved to have significant effects on social function and
      psychological symptoms. Each of the three "syndromic" axes (Axis I, Axis II, and
      Axis III) had a significant impact on social function and psychological symptoms.
      Only Axis III produced differences in somatic symptoms. The social and cultural
      implications of these results are discussed.

PMID- 8306642
TI  - Cross-cultural psychiatry and the DSM-IV.
AB  - This report attempts to provide a theoretical framework for exploring the
      intersection between current work in psychiatric nosology and cross-cultural
      psychiatry. Three positions at this intersection are constructed and contrasted-
      a clinical approach, an anthropological approach, and a synthetic clinical
      anthropological approach. These positions are used to consider a number of cross
      cultural issues in the forthcoming DSM-IV, including a background statement, a
      cross-cultural axis, diagnostic categories and criteria, and culture-bound
      syndromes.

PMID- 8306644
TI  - A note on the selection of control groups and control variables in comorbidity
      research.
AB  - Recently, investigators have become interested in "comorbidity" in eating
      disorders (EDs). However, it appears that many investigators fail to appreciate
      that demonstrating that ED patients have more of a given type of concomitant
      psychopathology than would be expected by chance requires the rejection of the
      following two null hypotheses: H0-1, Persons with EDs have no more symptomatology
      of the putatively comorbid condition than do persons without ED; and H0-2,
      Persons with EDs have no more symptomatology of the putatively comorbid condition
      than they have other kinds of psychopathology not specific to ED. The choice of
      proper control group for testing H0-1 and the necessity of testing H0-2 are
      illustrated with simulated data. These same general issues apply to the
      assessment of comorbidity in other conditions, but the appropriate comparison
      group obviously changes according to the exact hypothesis being tested.

PMID- 8306643
TI  - Social factors in alexithymia.
AB  - Social characteristics of alexithymic individuals were examined in a population
      based study of 2,682 middle-aged men from Eastern Finland. Alexithymia, referring
      to difficulties in identifying and verbally describing inner feelings, was
      assessed using the Toronto Alexithymia Scale (TAS). Men whose high TAS score
      suggested reduced ability in verbal emotional expression were more often
      unmarried and had low levels of social contacts and acquaintances. Education,
      income, and occupational status were inversely related to the TAS score. These
      associations remained statistically significant after adjustment for confounding
      factors. The results suggest that alexithymia could be viewed not only as a
      psychological phenomenon, but also partly as a socially determined one.

PMID- 8306645
TI  - Trichotillomania.
AB  - The present study examines some of the beliefs about trichotillomania such as
      those concerning the sex and age of afflicted individuals. Information was
      gathered from an exhaustive literature review and surveys of the general public
      and college students. Data on such factors as prevalence, sex, age distribution,
      onset, codiagnosis, and details of the hair-pulling act are presented, and
      reviews of explanations and treatment are provided.

PMID- 8306646
TI  - Correlates of pathological gambling propensity in prison inmates.
AB  - The South Oaks Gambling Inventory was administered to 136 consecutively admitted
      inmates in a medium-security prison in Nevada. According to the criteria of the
      authors of this instrument, 22.79% of these inmates had some problem and 26% were
      probable pathological gamblers. Significant positive correlations with the F,
      depression, psychopathic deviate, psychasthenia, paranoia, schizophrenia, and Mac
      Andrew alcoholism scales of the Minnesota Multiphasic Personality Inventory
      (MMPI) were found. Gambling score was negatively correlated with the Raven's
      Standard Progressive Matrices measure of intelligence. Clinical implications are
      suggested.

PMID- 8306647
TI  - Different perspectives of short-term changes in the rehabilitation of
      schizophrenic patients.
AB  - In the rehabilitation of schizophrenic patients, changes and outcome are usually
      assessed by members of multiprofessional therapeutic teams and by the patients
      themselves. In this study, the correlations of different perspectives of change
      during rehabilitation were investigated. After admission to a partial
      hospitalization program (printing workshop), 12 schizophrenic patients were
      examined weekly; the test period lasted 12 weeks. Ratings concerning various
      aspects of behavior were independently made by the patients themselves, by a work
      therapist, and by a psychiatrist, and week-by-week changes were analyzed. Factor
      analysis and correlations among change scores suggest a moderate to high
      homogeneity of each psychiatrist's and work therapist's ratings. Correlations
      among the three perspectives of change show little substantial concordance.
      Consequences for the practical work of multiprofessional teams in the
      rehabilitation of schizophrenic patients are discussed.

PMID- 8306648
TI  - A comparison of personality characteristics of seasonal and nonseasonal major
      depression.
AB  - During the acute depressive episode, seasonal affective disorder (SAD) patients
      (N = 24) differ significantly from non-SAD major depressives (N = 17) on five of
      13 personality variables measured, although severity of depression appears to be
      similar. SAD patients score significantly lower on the self-criticism and
      dependency dimensions of the Depressive Experiences Questionnaire (DEQ) and
      significantly higher on three personality trait scales (including schizotypal,
      narcissistic, and avoidant) of the Millon Clinical Multiaxial Inventory (MCMI).
      Our data suggest that those with seasonal depression may represent a
      psychologically distinct subgroup of depressives.

PMID- 8306649
TI  - What causes atresia coli in Holstein calves?

PMID- 8306650
TI  - Brain abscess in a goat.
AB  - A young goat was presented with a left spastic hemiparesis and general
      proprioceptive ataxia with postural reaction deficits, a right head tilt and
      positional nystagmus. Seizure-like activity was elicited by rapid changes in the
      position of the animal's head. The neurological signs and quality of the seizure
      activity suggested a lesion involving the medulla and possibly the cerebellum. A
      focal lesion at the level of the left cerebellar peduncles could explain the left
      hemiparesis and right paradoxical vestibular signs. A large encapsulated abscess
      was found at the confluence of the left cerebellar peduncles. The morphology and
      staining characteristics of the organisms within the abscess were consistent with
      Corynebacterium pseudotuberculosis.

PMID- 8306651
TI  - Ethmoid adenocarcinoma perforating the cribriform plate in the horse.
AB  - This clinical report describes an 8-year-old Thoroughbred mare that was presented
      for evaluation of a chronic, unilateral nasal discharge. Findings on physical
      examination, radiology, and video-endoscopy supported a clinical diagnosis of
      ethmoidal hematoma. After surgical ablation of the mass a defect was detected in
      the cribriform plate. At necropsy a 1.5 cm aperture was identified in the left
      cribriform plate allowing direct communication between the fundus of the nasal
      cavity and the cranium. Histology of the mass identified tissue consistent with
      an adenocarcinoma. History of profuse epistaxis warrants further investigation to
      differentiate malignant lesions from the more common benign lesions. During
      surgical ablation of large, space-occupying masses of the caudodorsal nasal
      cavity the cribriform plate should be examined for defects or secondary erosive
      lesions.

PMID- 8306652
TI  - Repeated canine herpesvirus (CHV) reactivation in dogs by an immunosuppressive
      drug.
AB  - To examine the possibility of repeated reactivation of canine herpesvirus (CHV),
      2 serial treatments with the corticosteroid drug prednisolone (PD) were given at
      different periods following oral-nasal infection of pups and adult dogs. CHV was
      not recovered from infected, untreated dogs or from uninfected, treated controls.
      Viral reactivation of CHV, without clinical signs, was induced twice in 2/3
      adults and in 2/3 pups treated at intervals that ranged from 1 to 3 months
      following the initial infections. Highest viral titers were obtained from nasal
      swab samples, with lower titers found in the oral pharynx, penis or vagina. In
      some, but not all dogs, the infectivity titers of the nasal secretion samples
      were higher after the initial prednisolone treatments than after the second
      treatments. The duration of viral shedding after the second series of steroid
      treatments also was shorter than the shedding period following the initial
      reactivations. The results presented here suggest that latent CHV occurs in both
      pups and adults dogs following infection and that active infections, with viral
      shedding, may occur repeatedly for prolonged, but undetermined, periods.

PMID- 8306653
TI  - Combined enzyme and antimicrobial susceptibility profiles of caprine Pasteurella
      haemolytica serovar 2 respiratory tract isolates.
AB  - The present investigation describes a novel method of demonstrating strain
      diversity among Pasteurella haemolytica biovar A, serovar 2 (PhA2) nasal
      turbinate isolates from a flock of 32 experimental goats during a naturally
      occurring outbreak of pasteurellosis. After a 21 day conditioning period in a
      feedyard, 51 PhA2 isolates from 27 culture-positive goats were identified
      including 1 on day 22, 14 on day 25, 21 on day 39, and 15 on day 66. Each PhA2
      isolate was evaluated for its enzyme activity against 19 substrates with a
      commercial semiquantitative enzyme system and for its antimicrobial
      susceptibility with 12 drugs, resulting in 7 different enzyme profiles and 8
      different antimicrobial susceptibility profiles. A total of 14 combined enzyme
      and antimicrobial susceptibility profiles were produced. The same PhA2 strain was
      isolated from only 4 of the 12 goats with 2 PhA2 isolations, while the same PhA2
      strain was isolated from only 1 of the 6 goats with 3 PhA2 isolations. The data
      from this investigation demonstrated that the PhA2 upper respiratory tract flora
      from goats is highly heterologous.

PMID- 8306654
TI  - Reaction rate in cats vaccinated with a new controlled-titer feline panleukopenia
      rhinotracheitis-calicivirus-Chlamydia psittaci vaccine.
AB  - The safety profile of a new controlled-titer feline panleukopenia-rhinotracheitis
      calicivirus-Chlamydia psittaci vaccine was compared to that of a currently
      marketed vaccine. Of particular interest were delayed reactions (previously
      unreported in the literature in felines) occurring 7 to 21 days after
      vaccination, and the effect of concurrent vaccinations and cat age on the delayed
      reaction rate. Nineteen hundred twenty-four doses of the new vaccine and 364
      doses of the comparison vaccine were administered in 42 participating veterinary
      practices. The postvaccination evaluation period was 21 days. Reactions
      (anaphylaxis, short- and long-term lethargy, inappetence, pain, upper respiratory
      inflammation, delayed fever, anorexia, and miscellaneous events) were reported in
      3.33% of cats receiving the controlled-titer vaccine and in 3.02% of cats
      receiving the comparison vaccine. The difference was not statistically
      significant (P = 0.45). Reaction rate of the controlled-titer vaccine and that of
      the vaccine currently accepted by veterinarians appear to be equivalent.

PMID- 8306655
TI  - Renal failure in a calf secondary to chronic enteritis.
AB  - This clinical report describes a case of renal failure in a Holstein calf. It is
      suggested that the renal failure was hemodynamically-mediated. The combination of
      a chronic enteritis and failure to ingest adequate fluids produced the
      hyponatremia, hypochloremia, and metabolic acidosis. The elevated BUN,
      creatinine, FENa, and isosthenuria confirmed the diagnosis of renal failure.
      Continued testing of the heifer demonstrated persistence of the renal failure
      even though the heifer appeared normal on clinical examination. Monitoring the
      growth rate of the heifer calf demonstrated a severe reduction when compared to
      age-matched herdmates.

PMID- 8306656
TI  - In vivo confocal microscopic studies of endothelial wound healing in rabbit
      cornea.
AB  - Corneal endothelial wound healing in living rabbit eyes after mechanical scrape
      (MS) and transcorneal freeze (TCF) injury was studied using tandem scanning
      confocal microscopy (TSCM). MS injury was created on the central corneal
      endothelium with an olive tip cannula; TCF injury was created using a 3-mm
      diameter stainless steel probe cooled with liquid nitrogen. In vivo observation
      of wound healing using TSCM was correlated with scanning electron microscopy
      (SEM) for fixed tissues. At 6 h after MS, migrating endothelial cells at the
      leading edge showed lamellipodial processes on in vivo TSCM and SEM. After 24 h,
      the denuded area was almost fully resurfaced by migrating endothelial cells
      showing wide spaces between nuclei by TSCM. After 28 days, resurfaced endothelial
      cells showed normal hexagonal mosaic appearance with enlarged cells by TSCM and
      SEM. TCF injury produced fibroblastic changes in the endothelial cells with
      elongation and spreading by 24 h after injury. After 3 days, the wounded area was
      resurfaced with two cell types: (a) migrating endothelial cells at the peripheral
      area, which appeared polygonal in shape with wide intracellular spaces and (b)
      fibroblast-like cells at the center of the wound, which formed a retrocorneal
      fibrous membrane (RCFM). The RCFM was posteriorly covered with normal endothelium
      after 28-60 days. TSCM of the stroma demonstrated spindle-shaped, activated
      keratocytes migrating into the wounded stroma at 3-14 days. In conclusion, TSCM
      allows viewing of dynamic four-dimensional morphologic changes (x, y, z, and
      time) during in vivo cellular repair of corneal wound healing after either MS or
      TCF injury.

PMID- 8306657
TI  - Effect of doxycycline hyclate on corneal epithelial wound healing in the rabbit
      alkali-burn model. Preliminary observations.
AB  - We examined the effects of doxycycline hyclate on epithelial healing in vivo in
      the rabbit alkali-burn model. Twelve 2-3-kg Dutch belted rabbits were divided
      into three groups and received standard bilateral alkali burns (1 N sodium
      hydroxide for 30 s in an 11-mm circular plastic well). In group 1, two rabbits
      (four eyes) served as untreated controls. In group 2, five rabbits (10 eyes)
      received doxycycline hyclate (1.5 mg/kg) orally daily for 14 days. In group 3,
      five rabbits (10 eyes) received doxycycline hyclate (5 mg/kg) orally daily for 14
      days. The epithelial defects were drawn and photographed on alternate days, after
      fluorescein staining. At conclusion, extracts of the corneas were evaluated for
      collagenase activity. At 14 days, the mean percentage of epithelial defects
      results in groups 1-3 were 50.0, 50.7, and 7.1%, respectively. Using the Wilcoxon
      rank sum test (two tailed), the differences were found to be statistically
      significant (p = 0.0015). Preliminary data indicated that oral doxycycline
      administration also decreased the collagenase activity in corneas obtained from
      these animals. Our preliminary findings indicated that systematically
      administered doxycycline hyclate, 5 mg/kg/day, promotes corneal
      reepithelialization in the rabbit alkali-burn model, a result, perhaps, of the
      drug's ability to inhibit excessive collagenase activity.

PMID- 8306658
TI  - Epithelial basement membrane in alkali-burned corneas in rats.
      Immunohistochemical study.
AB  - We investigated the altered immunolocalization of the components of epithelial
      basement membrane (BM) in rats with alkali burns of the cornea. Type IV collagen,
      laminin, and fibronectin were immunohistochemically stained in the alkali-burned
      corneas after various intervals. Linear laminin immunoreactivity, which
      represented the localization of the BM, was interrupted, probably by epithelial
      enzymes, under the regenerating epithelium after 24 h. A normal configuration was
      restored on day 7, when the central corneal BM showed a type IV collagen
      immunoreactivity that was not detected in BM of normal cornea. The exact cause of
      the development of type IV collagen immunoreactivity in the healing BM was not
      determined. Laminin, type IV collagen, and fibronectin, which were not detected
      in normal stroma, were all detected in the healing corneal stroma with
      repopulated keratocytes. Moreover, the BM zone under the regenerating epithelium
      showed fibronectin immunoreactivity on days 5-14. Distribution of these
      components of BM seemed to be normal 2 months postburn. The alteration of BM
      components is thought to be an important marker of the healing process in corneas
      burned with alkali.

PMID- 8306659
TI  - Suppression of human corneal epithelial proliferation with breast carcinoma
      immunotoxin.
AB  - We examined the effects of the immunotoxin 260F9 Mab-recombinant ricin A
      (developed against human breast carcinoma) on proliferating and confluent human
      corneal epithelium (HCE) cells in vitro. HCE cells derived from explants of
      discarded human donor corneoscleral rims were established as proliferating and
      confluent cell cultures, and were exposed continuously for 7 days to immunotoxin.
      Final cell counts at day 7, and thymidine uptake measured at days 1 and 7
      postexposure, showed > 95% suppression of proliferating cells at an immunotoxin
      concentration of 10 ng/ml, with confluent HCE cells relatively unaffected. This
      immunotoxin may prove useful in treatment of proliferative ocular epithelial
      diseases such as epithelial downgrowth or squamous cell carcinoma of the ocular
      surface.

PMID- 8306660
TI  - Control of astigmatism aided by intraoperative keratometry.
AB  - An evaluation of the final "sutures out" postoperative astigmatism in two groups
      of keratoconus patients undergoing penetrating keratoplasty is presented. Group I
      consists of a retrospective evaluation of keratoconus patients who underwent
      penetrating keratoplasty without using the Troutman Keratometer prior to suturing
      the button into position. Group II patients had their donor button rotated in the
      recipient bed until approximate sphericity was indicated by a circular reflex
      from the Troutman Keratometer before suturing into position. The mean final
      astigmatism with all sutures removed from Group I was 4.64, SD 1.89, and for
      Group II 2.27, SD 1.27. Selective positioning of the donor button using the
      Troutman Keratometer leads to a significant reduction in the final sutures out
      astigmatism in patients undergoing penetrating keratoplasty for keratoconus.

PMID- 8306661
TI  - A comparison between donor-recipient corneal size and its effect on the ultimate
      refractive error induced in keratoconus.
AB  - A prospective randomized clinical study was performed to see the effect of donor
      recipient corneal size on the ultimate refractive error induced in keratoconus at
      our facility. The patients were randomly divided into two groups, A and B. In
      Group A, the difference in size between the donor and the recipient cornea was
      0.25 mm (18 patients). In Group B, the difference in size between the donor and
      the recipient cornea was 0.50 mm (20 patients). Both groups underwent the
      surgical procedure with the same surgeon (M.A.J.) and the same technique. Two
      months after suture removal, keratometry readings and refractive errors induced
      were compared. The mean keratometry reading in Group A was 43.3 diopters; in
      Group B, the reading was 44.8 diopters. There was a mean difference of 1.5
      diopters between the two groups (p = 0.01). The mean refractive error in terms of
      spherical equivalent in Group A was -1.55 diopters and in Group B was -3.33
      diopters. There was a difference of -1.8 diopters between the two groups (p <
      0.05).

PMID- 8306663
TI  - Topical cyclosporin A in the treatment of anterior segment inflammatory disease.
AB  - Topical cyclosporin A was used in the management of 43 patients with a variety of
      anterior segment inflammatory disorders that had failed corticosteroid treatment.
      Treatment with topical cyclosporin A ranged from 1 week to 43 months, with a mean
      treatment period of 13 months. Thirty-five patients (81%) with disorders
      including high-risk keratoplasty, atopic and vernal keratoconjunctivitis,
      ligneous conjunctivitis, ulcerative keratitis, and Mooren's ulcer had a
      beneficial result, with resolution, reduction, or prevention of inflammation. Six
      patients (14%) with scleritis, ocular cicatricial pemphigoid, or endothelitis
      showed no clinical improvement. Two patients (5%) had significant ocular
      discomfort, and the drug had to be discontinued in them. None of the other
      patients developed local side effects. Twenty-seven of these patients were
      followed with serial cyclosporin A blood levels and serum creatinine. None of
      these patients developed measurable drug blood levels or renal toxicity.

PMID- 8306662
TI  - West Indian punctate keratopathy.
AB  - We found corneal lesions of West Indian punctate keratopathy in 128 of 2,048
      patients examined in a general eye clinic in Grenada, West Indies. Of these, 125
      were Black, two were Indians (Hindu), and one a White female. The lesions
      occurred in asymptomatic persons with no history of trauma or recurrent erosions.
      Males were affected more than females, and older adults more than children. The
      condition was usually unilateral but occasionally bilateral, with one to four
      lesions in the intrapalpebral fissure in a paracentral location. The lesions were
      round, discrete, white to yellowish-gray dots 0.2-0.6 mm in size located at the
      level of the epithelial basement membrane and Bowman's layer. No vascularization
      nor other anterior membrane disorders were observed. Corneal biopsies of 11
      patients were studied by histopathologic and immunoperoxidase techniques.
      Histopathology revealed areas of lipid positive material in Bowman's layer and
      adjacent corneal stroma. The epithelium showed basal cell edema, degeneration,
      and irregular thickening of the basement membrane. Immunoperoxidase studies did
      not contribute any new information about these lesions.

PMID- 8306664
TI  - Regulation of corneal fibroblast MMP-1 collagenase secretion by plasmin.
AB  - Plasmin was found to degrade the fibronectin (Fn) mesh produced by cultures of
      normal rabbit corneal fibroblasts, cause breakdown of F-actin-containing
      microfilament bundles ("stress fibers"), and increase levels of active type I
      interstitial collagenase (MMP-1) in the medium. Fibroblast cultures derived from
      alkali-burned, ulcerating rabbit corneas also responded to plasmin by secreting
      collagenase, detected only in active form. Moreover, harvests from organ cultures
      of ulcerating corneas not only had higher levels of urokinase-like plasminogen
      activator (uPA) than normal cultures but also had higher levels of Fn degradation
      fragments. The results are consistent with reports that indicate that
      perturbation of the alpha 5 beta 1 integrin (Fn) receptor by proteolytic
      fragments of Fn causes the increased synthesis and secretion of MMP-1. The
      uPA/plasmin system, therefore, might have an important role in regulating
      collagenase synthesis, secretion, and activation during wound remodelling and
      stromal ulceration.

PMID- 8306666
TI  - Residual cornea and the degenerate eye of the cryptophthalmic Typhlotriton
      spelaeus.
AB  - The cave-dwelling Typhlotriton spelaeus larvas live in daylight. The larvas
      undergo a metamorphosis when the thyroxin level (T3 and T4) increases. They leave
      aquatic life for terrestrial and subterranean aphotic life. The larval eyes are
      normal and show good vision response to tests. On the contrary, in the oldest
      larva and the adult, the eyes are small with poor vision or no vision at all. The
      lens can disappear but in any case the eyelids grow over the eye. The retinal
      degeneration takes place during and after metamorphosis. The admitted statement
      that "after metamorphosis . . . the developing lids close over the eye and invade
      the cornea" is not confirmed concerning the invasion, because it is now evident
      that the eyelids separate spatially from the residual cornea. Consequently, the
      fibroblasts of the eyelids are not able to invade the corneal stroma. In fact,
      the periocular tissues do not invade the cornea but invade the eyelids' tissues.
      We are able to confirm that the development of the larval eyes is complete and
      apparently normal. After metamorphosis, the eyes decrease in size. The cornea
      "sinks" with the eye into orbit tissues. The eyelids cover the eye and are
      themselves replaced by a supraocular skin. This fits the description of the human
      cryptophthalmia. We also demonstrate that even in the degenerate eye the residual
      cornea retains the main structure of a normal salamander cornea. The preservation
      of the endothelium and of the Descemet membrane is exceptional in blind cave
      dwelling vertebrates because in the other degenerate corneas the edema of the
      stroma depends on the spatial disjunction of the underepithelial stroma and the
      supraendothelial stroma. Perhaps, the very advanced development of the eye and
      the late start of the degenerative processes could explain the relative
      preservation of the cornea. Thus, the arguments put forward tend to prove that
      the thyroxinic metamorphosis sets off the growth and fusion of the eyelids but
      that the eye degeneration is related to hereditary processes.

PMID- 8306665
TI  - Characterization of water retentive properties of hyaluronan.
AB  - We examined the water retentive properties of hyaluronan because of its reported
      therapeutic effect in the treatment of dry eye. Hyaluronan dose dependently
      retarded water loss from a solution kept at constant temperature and humidity.
      Similarly, water loss was retarded when hyaluronan was placed atop an agar gel.
      These decreases in water loss were not related to changes in the molecular weight
      of hyaluronan. Unlike the in vitro models, the evaporation rate from the tears in
      normal subjects initially increased following the topical application of
      hyaluronan, and continued a higher rate than with the vehicle. These results
      suggest that hyaluronan enhances water retention on the corneal surface, and
      probably increases corneal wettability. Accordingly, hyaluronan eye drops may be
      useful in the treatment of dry eye.

PMID- 8306667
TI  - Intraepithelial corneal immunoglobulin crystals in IgG-kappa multiple myeloma.
AB  - A 52-year-old man was first examined because of bilateral superficial punctate
      keratitis. Slit-lamp examination disclosed numerous intraepithelial minute
      opacities in both corneas. A corneal biopsy revealed intraepithelial rhomboidal
      or rectangular crystals that immunohistochemically stained only for IgG-kappa.
      Serum immunoelectrophoresis demonstrated an IgG-kappa monoclonal gammopathy. Over
      the ensuing 6 years, the clinical appearance of the crystals changed from small
      dot-like opacities to polychromatic crystals. At this time, bone marrow
      examination established the diagnosis of multiple myeloma. Ophthalmologists
      should be aware of this entity and carefully monitor these patients; the corneal
      lesions may be the initial manifestation of an asymptomatic monoclonal gammopathy
      preceding the development of multiple myeloma.

PMID- 8306668
TI  - Anterior corneal dystrophy with dyscollagenosis (Reis-Bucklers type?).
AB  - Anterior corneal dystrophies involving Bowman's membrane and anterior stroma
      include several subtypes of uncertain etiology: the Reis-Buckler, Thiel-Behnke,
      Grayson-Wilbrandt, and "honeycomb" dystrophies. The clinical and pathologic
      features of these dystrophies overlap to such a degree that they may represent
      variations of the same entity. Typically, they all present symptoms beginning in
      childhood, have a dominant pattern of heredity, and manifest painful, recurrent
      corneal erosions. Some cases have also been interpreted as representing macular
      and granular dystrophy. In the present report, we describe a pedigree of affected
      patients whose corneal dystrophy shared many of the clinical and pathologic
      features of the Reis-Bucklers and allied subtypes but which differ from all in
      causing visual symptoms late in life and with minimal signs of recurrent erosion.
      Histopathology revealed a thickening of the anterior stroma by the addition of a
      partially disorganized and degenerating tissue in which collagen Type III (fetal
      or repair collagen) is intermixed with the normal (mature) Type I collagen in the
      entire stroma. This is accompanied by irregular swelling of the basal epithelial
      cells and hyperplasia of the basement membrane (collagen Type IV, laminin and
      fibronectin), suggesting an aberrant influence of the epithelium on collagen
      synthesis.

PMID- 8306669
TI  - Too little oxygen, too little interleukin-2: a link between hypoxemia and
      cellular immune dysfunction.

PMID- 8306670
TI  - How stable is a "stable" cardiac output?

PMID- 8306671
TI  - Preventing cardiac arrest.

PMID- 8306672
TI  - Time to consider early gut feeding.

PMID- 8306673
TI  - On the threshold of a dream.

PMID- 8306674
TI  - The controversies in cardiopulmonary resuscitation on high-dose epinephrine still
      continue.

PMID- 8306675
TI  - Central venous access risk factors.

PMID- 8306676
TI  - Effects of hypoxia on interleukin-2 mRNA expression by T lymphocytes.
AB  - OBJECTIVE: To investigate the effects of hypoxia on T-lymphocyte expression of IL
      2 messenger RNA (mRNA), after cell activation with phorbol ester and ionomycin.
      DESIGN: Prospective, controlled, cellular trial. SETTING: University research
      laboratory. SUBJECTS: EL4.6.1 cells, a murine T-cell lymphoma line.
      INTERVENTIONS: Tissue culture media was deoxygenated and flushed continuously
      with 100% helium to maintain a PO2 of 30 to 40 torr (< 40 torr [< 5.3 kPa]), or
      flushed with 10% oxygen/90% helium to maintain a PO2 of 45 to 55 torr (> 45 torr
      [> 6.0 kPa]). The pH was maintained between 7.3 and 7.6. The media was inoculated
      with EL4 cells. Aliquots of cells were obtained at intervals and divided into two
      groups: an immediate group, stimulated immediately, and an overnight group that
      was returned to normal incubator conditions of 5% CO2/humidified room air for 18
      hrs before stimulation. MEASUREMENTS AND MAIN RESULTS: Gas tension, pH, cell
      count, and viability were determined for each aliquot. Cells were stimulated with
      phorbol myristate acetate and ionomycin for 4 hrs, at which time levels of
      interleukin-2 (IL-2) messenger RNA (mRNA) and gamma actin mRNA were measured by
      solution hybridization and enzyme immunoassay. The results were expressed as IL-2
      mRNA/gamma actin mRNA ratio, normalised to baseline room air values. Cell
      viability and housekeeping functions (gamma actin mRNA expression) were
      unaffected by hypoxia. Cells exposed to a PO2 of < 40 torr (< 5.3 kPa)
      demonstrated a dramatic reduction in IL-2 mRNA expression with increasing
      duration of hypoxia. These effects persisted after an 18-hr recovery period.
      There was no effect on IL-2 mRNA expression when cells were exposed to a PO2 of >
      45 torr (> 6.0 kPa). CONCLUSIONS: The regulation of IL-2 transcription in the T
      lymphocyte appears to be exquisitely sensitive to changes in oxygen tension.
      Exposure to a PO2 of < 40 torr (< 5.3 kPa) causes prolonged impairment of IL-2
      mRNA expression. IL-2 is an important growth factor for T and NK cells, and plays
      a pivotal role in the regulation of the host's immune response. The long-lasting
      effects of brief hypoxic exposure may, in part, explain the critically ill
      patient's predisposition to infectious complications.

PMID- 8306677
TI  - Plasma degradation of platelet-activating factor in severely ill patients with
      clinical sepsis.
AB  - OBJECTIVE: To study the plasma degradation of platelet-activating factor in
      severely ill patients with clinical sepsis. DESIGN: A prospective, nonrandomized
      control study. SETTING: Intensive care unit in a university hospital. PATIENTS:
      Thirteen critically ill male patients with clinical sepsis, due to medical or
      surgical illness, and ten normal male volunteers were studied. Measurements were
      repeated in seven patients who survived. MEASUREMENTS AND MAIN RESULTS: The
      plasma activity of acetylhydrolase, the lipoprotein-associated enzyme that
      hydrolyses platelet-activating factor to its biologically inactive lyso
      derivative was determined using an optimized enzyme assay. The plasma half-life
      of platelet-activating factor was also measured, along with phospholipase A2
      activity, lyso-platelet-activating factor, and serum lipid concentrations.
      Patients results were compared with those results of normal controls and followed
      once in survivors. Acetylhydrolase activity in the patient group was
      significantly lower than in normal subjects (median 34, interquartile range 17 to
      54 nmol/min/mL vs. median 60, interquartile range 56 to 80 nmol/min/mL; p <
      .002), while overall, the plasma half-life of platelet-activating factor did not
      differ significantly between the groups. However, the half-life of platelet
      activating factor in six patients who died (median 3.3, range 3.3 to 4.3 mins)
      was significantly greater than in either survivors (median 2.1, range 1.4 to 2.9
      mins; p < .001) or the normal group (median 2.5, range 2.2 to 2.8 mins; p <
      .001). Consistent with theoretical prediction, a significant linear relationship
      existed between platelet-activating factor half-life and the reciprocal of
      acetylhydrolase activity in the patient group (p < .05). Plasma phospholipase A2
      activity was markedly increased in the patient group, while plasma lyso-platelet
      activating factor and serum lipid concentrations were severely decreased.
      CONCLUSIONS: Depression of acetylhydrolase activity was consistent with the
      concentration of lipids with which it is associated. Platelet-activating factor
      half-life was relatively well preserved because of the nature of its relationship
      with enzyme activity. The half-life was prolonged in those patients with the
      worst outcome and the breakdown in plasma degradation of platelet-activating
      factor could have contributed to pathophysiology in these subjects.

PMID- 8306678
TI  - High atrial natriuretic peptide concentrations blunt the pressor response during
      cardiopulmonary resuscitation in humans.
AB  - OBJECTIVE: To determine the relationship of circulating atrial natriuretic
      peptide concentrations to the pressor response to high-dose epinephrine in
      patients undergoing cardiopulmonary resuscitation (CPR) for cardiac arrest.
      DESIGN: Prospective study. PATIENTS: Fourteen normothermic, adult, prehospital
      and emergency department patients suffering unexpected cardiac arrest.
      INTERVENTION: Patients received high-dose epinephrine (0.2 mg/kg) i.v. when
      standard advanced cardiac life support (including multiple 1-mg dosages of
      epinephrine) failed to result in return of spontaneous circulation. MEASUREMENTS
      AND MAIN RESULTS: Cardiac arrest patients were separated into those patients with
      and without detectable serum atrial natriuretic peptide concentrations, and were
      termed the "low atrial natriuretic peptide" and "high atrial natriuretic peptide"
      groups, respectively. Their aortic pressure response to high-dose (0.02 mg/kg)
      epinephrine was compared. The proportion with positive assays was compared with a
      group of healthy control subjects. Fourteen patients were studied. Eight patients
      had low serum atrial natriuretic peptide concentrations and six patients had high
      circulating atrial natriuretic peptide concentrations. The mean concentration in
      the high atrial natriuretic peptide group was 151 +/- 82 pg/mL. The proportion
      with positive assays (six of 14 patients) was greater than in the group in
      spontaneous circulation (three of 29 patients) (p = .002). The maximal increase
      in the aortic relaxation-phase pressures after high-dose epinephrine was 9 +/- 7
      torr (1.2 +/- 0.9 kPa) in the low atrial natriuretic peptide group and 0 +/- 5
      torr (0 +/- 0.7 kPa) in the high atrial natriuretic peptide group (p = .03). The
      maximal increase in the aortic compression pressures after high-dose epinephrine
      was 17 +/- 13 torr (2.3 +/- 1.7 kPa) in the low atrial natriuretic peptide group
      and 2 +/- 10 torr (0.3 +/- 1.3 kPa) in the high atrial natriuretic peptide group
      (p = .03). Thus, pressor responses after high-dose epinephrine administration
      were observed in patients in the low atrial natriuretic peptide group, but this
      response was absent in patients in the high atrial natriuretic peptide group.
      CONCLUSIONS: Cardiac arrest patients receiving CPR have higher circulating atrial
      natriuretic peptide concentrations than healthy subjects. High serum atrial
      natriuretic peptide concentrations may antagonize the vasopressor response to
      epinephrine. Blocking this effect of atrial natriuretic peptide may improve
      outcomes in patients suffering cardiac arrest.

PMID- 8306679
TI  - Inferior vena caval pressure reliably predicts right atrial pressure in pediatric
      cardiac surgical patients.
AB  - OBJECTIVE: To compare "central venous pressure" in pediatric patients in a
      clinical setting as measured from catheters in the infrahepatic inferior vena
      cava and the right atrium. DESIGN: Prospective, unblinded study. SETTING:
      Cardiothoracic intensive care unit of a tertiary care university hospital.
      PATIENTS: Thirty-three pediatric cardiac surgical patients, 2 days to 92 months
      of age (mean 24 +/- 4 months). INTERVENTIONS: All patients had intraoperative
      placement of an 8-cm, double-lumen, femoral venous catheter and a transthoracic
      right atrial catheter. Patients were studied for 0 to 2 days after surgery.
      MEASUREMENTS AND MAIN RESULTS: Measurements were obtained during mechanical and
      spontaneous ventilation. Although not statistically identical, measurements of
      "central" venous pressure in the inferior vena cava and right atrium correlated
      well (r2 = .87 for mechanical ventilation; r2 = .83 for spontaneous ventilation).
      Of 31 data pairs in mechanically ventilated patients, the absolute difference in
      pressures was as large as 3 mm Hg in three patients and <3 mm Hg in all the rest.
      In 15 spontaneously breathing patients, there were only three data measurements
      where the difference in pressure was 2 mm Hg and none of the differences was
      greater. In spontaneously breathing patients, the phasic changes due to
      respiratory variations in venous pressure were in phase in both the intrathoracic
      and intra-abdominal catheter positions. CONCLUSIONS: We conclude that while
      "central" venous pressures measured in the inferior vena cava and in the right
      atrium are not statistically identical, any differences are well within
      clinically important limits. Placement of central venous pressure catheters in
      the inferior vena cava by the femoral venous approach is a reliable alternative
      to cannulating the superior vena cava in pediatric patients without clinically
      important intra-abdominal pathology and with anatomic continuity of the inferior
      vena cava with the right atrium. Relatively short femoral vein catheters allow
      adequate measurement of central venous pressure without concern for exact
      catheter tip position and without the risk of right atrial perforation,
      intracardiac arrhythmias, and inadvertent puncture of carotid and intrathoracic
      structures. Unlike previously reported results in neonates, we found that the
      phasic changes of venous pressure with the respiratory cycle were similar in both
      intrathoracic and intra-abdominal recordings, making this an inappropriate
      clinical indicator of venous catheter tip position.

PMID- 8306680
TI  - Variability of cardiac output over time in medical intensive care unit patients.
AB  - OBJECTIVES: To determine the amount of spontaneous variability of cardiac output
      over time in critically ill patients, and to determine the effect of mechanical
      ventilation on cardiac output variability over time. DESIGN: Case series.
      SETTING: Medical intensive care unit in a Veterans Affairs Medical Center.
      PATIENTS: Twenty-two patients with indwelling pulmonary artery flotation
      catheters were studied. Two patients were studied twice. INTERVENTIONS: During a
      1-hr time period in which no interventions were required or made, thermodilution
      cardiac output was determined at baseline and then every 15 mins for 1 hr. At
      each time point, five individual cardiac output measurements were made and a mean
      was computed. The covariables of heart rate, respiration rate, mean arterial
      pressure, mean pulmonary arterial pressure, pulmonary artery occlusion pressure,
      and temperature were also recorded at each time point. MEASUREMENTS AND MAIN
      RESULTS: The variability of the five cardiac output measurements made at each
      time point was expressed by calculating for each patient a coefficient of
      variation of the measurements. The overall mean coefficient of variation of the
      measurements was 5.8%. The variability of the cardiac output measurements over
      time was expressed by calculating for each patient a coefficient of variation
      over time. The overall mean coefficient of variation over time was 7.7%. A
      subgroup of 15 "covariable stable" patients (defined as those patients with
      covariables within +/- 5% of the mean covariable values during the hour) had a
      mean coefficient of variation over time of 6.4%, whereas "covariable unstable"
      patients (with > +/- 5% changes in any covariable) had a mean coefficient of
      variation over time of 9.9% (p < .05). Patients breathing spontaneously had a
      mean coefficient of variation over time of 10.1%, whereas mechanically ventilated
      patients had a mean coefficient of variation over time of 6.3% (p < .05).
      CONCLUSIONS: The spontaneous variability of cardiac output should be considered
      when interpreting two cardiac output determinations made at separate times. Due
      to spontaneous variability alone, a patient with a baseline cardiac output of
      10.0 L/min would be expected (95% confidence interval) to have a cardiac output
      range of 9.2 to 10.8 L/min if covariables were stable, and a range of at least
      8.8 to 11.2 L/min if covariables were unstable. Patients who were mechanically
      ventilated displayed less variability than patients who were breathing
      spontaneously.

PMID- 8306681
TI  - Changing patterns of terminal care management in an intensive care unit.
AB  - OBJECTIVE: To empirically describe changes in terminal care management behavior
      over time with the advent of natural death acts and public dialogue and
      institutional policy regarding terminal care. DESIGN: Retrospective analysis of
      medical decision-making and outcome was performed in a cohort of 237 intensive
      care unit (ICU) patients who received a do-not-resuscitate decision. SETTING:
      Medical ICU in a tertiary care center. PATIENTS: The cohort of 237 consecutive
      patients who received a terminal care decision in the ICU, i.e., a do-not
      resuscitate decision with or without additional limitation of care, represented
      9.3% of 2,185 patients admitted to the ICU over a 4-yr period. Brain-dead
      patients were excluded from the cohort. INTERVENTIONS: Implementation of hospital
      wide policies on do-not-resuscitate decisions and discontinuation of life
      prolonging procedures in 1986. MEASUREMENTS AND MAIN RESULTS: A change in
      frequency and nature of terminal care decisions occurred. By 1988, do-not
      resuscitate decisions occurred twice as often as in 1984 (p = .016) compared with
      ICU deaths. Formal terminal wean decisions, i.e., additional limitation or
      withdrawal of care, occurred more frequently after 1985 (p = .027). The hospital
      mortality rate for the do-not-resuscitate cohort was 96.4% (226/237). The
      diagnosis of cardiac arrest was correlated with subsequent terminal care
      decisions (p = .0005, r2 = .08). Age of >56 yrs was increasingly correlated with
      probability of a terminal care decision (p < .0001, r2 = .05). White women
      received withdrawal of care most frequently, followed by white men, African
      American men, and African American women. Outcomes analysis indicated that after
      a do-not-resuscitate decision, most nonsurvivors died within 48 hrs. Eleven
      patients without additional limitation or withdrawal of care survived to hospital
      discharge (11/237 [4.6%]). No patient survived a terminal wean. CONCLUSIONS:
      There is now an increasing probability that impending death will be acknowledged
      by a formal terminal care decision. Such decisions may become even more frequent
      with the dialogue generated by the Patient Self Determination Act and the advent
      of decisions based on physiologic futility.

PMID- 8306682
TI  - Developing strategies to prevent inhospital cardiac arrest: analyzing responses
      of physicians and nurses in the hours before the event.
AB  - OBJECTIVES: To determine: a) the frequency of premonitory signs and symptoms
      before cardiac arrest in patients on the general medical wards of a hospital; b)
      any characteristic patterns in nurse and physician responses to these signs and
      symptoms; and c) whether cardiac arrests on the ward occur more frequently in
      patients discharged from the medical intensive care unit (ICU) than in other
      patients. DESIGN: Case series of consecutive patients who had an inhospital
      cardiac arrest over a 20-month period. SETTING: General medical wards of a 1,000
      bed urban public hospital. PATIENTS: There were 21,505 total admissions to the
      medical service in this period. Patients whose cardiac arrests occurred in the
      Emergency Room and ICU and patients with do-not-resuscitate orders were excluded
      from the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a
      total of 150 cardiac arrests on the medical wards (cardiac arrest rate: 7.0/1,000
      patients) with a hospital mortality rate of 91%. In 99 of 150 cases, a nurse or
      physician documented deterioration in the patient's condition within 6 hrs of
      cardiac arrest. Common findings included: a) failure of the nurse to notify a
      physician of a deterioration in the patient's mental status; b) failure of the
      physician to obtain or interpret an arterial blood gas measurement in the setting
      of respiratory distress; and c) failure of the ICU triage physician to stabilize
      the patient's condition before transferring the patient to the ICU. Former ICU
      patients (cardiac arrest rate: 14.7/1,000 patients) were more likely to suffer
      cardiac arrest than other patients (cardiac arrest rate: 6.8/1,000 patients) (p =
      .004). CONCLUSIONS: Cardiac arrests on the general wards of the hospital are
      commonly preceded by premonitory signs and symptoms. Strategies to prevent
      cardiac arrest should include training for nurses and physicians that
      concentrates on cardiopulmonary stabilization and how to respond to neurologic
      and respiratory deterioration. Special attention should also be devoted to
      patients who have been discharged from the ICU who are at greater risk for
      cardiac arrest after ICU discharge than are other medical patients.

PMID- 8306684
TI  - Hyponatremia in acute spinal cord injury.
AB  - OBJECTIVE: To define the occurrence rate, time course, and potential etiologic
      factors of hyponatremia in patients with acute spinal cord injury. DESIGN:
      Analysis of data obtained from a retrospective review of medical records and from
      a systematized, prospective database pertaining to patients with spinal cord
      injury. SETTING: A university hospital with a federally funded regional spinal
      cord injury center and a dedicated spinal cord injury intensive care unit.
      PATIENTS: Two hundred eighty-two patients admitted between January 1, 1988 and
      December 31, 1989 with acute (< 24-hr duration) spinal cord or vertebral column
      injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean age of
      patients was 36.7 +/- 17.6 (SD) yrs; 225 (80%) of the patients were male and 57
      (20%) were female. Hyponatremia, when it occurred, developed at a mean time of
      6.4 +/- 6.7 days postadmission, reached its nadir at 8.7 +/- 8.8 days, and
      occurred in 28% of those patients with cervical injuries, 34% with thoracic
      injuries, and 27% with lumbar injuries (p = NS). Logistic regression analysis
      demonstrated that the type of spinal cord injury (Frankel class: range is A =
      complete neurologic lesion to E = no neurologic lesion) was the strongest
      predictor of hyponatremia. The occurrence rate of hyponatremia was as follows:
      Frankel class-A 62%; Frankel class-B 48%; Frankel class-C 41%; Frankel class-D
      23%; Frankel class-E 16% (p < .0001). CONCLUSIONS: The prevalence of hyponatremia
      in acute spinal cord injury is much higher than in the general medical or
      surgical patient population. This abnormality usually occurs within the first
      week postinjury. The most significant predictor of hyponatremia is the type
      rather than the level of spinal cord injury. The potential etiological factors
      are many and these factors are probably interrelated. The pathophysiological
      mechanisms that result in hyponatremia must be explored so that this occurrence
      and its consequences can be prevented.

PMID- 8306683
TI  - Effects of intravenous medium-chain triglycerides on pulmonary gas exchanges in
      mechanically ventilated patients.
AB  - OBJECTIVE: In mechanically ventilated patients, pulmonary gas exchange was
      investigated during the administration of total parenteral nutrition containing
      medium-chain triglycerides or long-chain triglycerides as fat emulsions. DESIGN:
      Prospective, randomized, crossover trial (two lipid infusion periods of 8 hrs).
      SETTING: Intensive care unit in a university hospital. PATIENTS: Six mechanically
      ventilated patients, using the pressure-support mode. INTERVENTIONS: Total
      caloric intake was adapted according to measured energy expenditure. Fat emulsion
      provided 50% of the energy expenditure. Patients were infused with 50% medium
      chain/50% long-chain triglycerides or 100% long-chain triglycerides in a random
      sequence. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption, CO2 production, and
      minute ventilation were measured by indirect calorimetry. PaO2 and PaCO2 were
      determined in blood samples. Medium-chain triglycerides increased oxygen
      consumption by 27.8% and minute ventilation by 14.3% at the end of the protocol.
      CO2 production, PaO2, and PaCO2 were not different between groups. CONCLUSIONS:
      Medium-chain triglycerides cause an increase in metabolic demand in mechanically
      ventilated patients when they are infused over a short period. Postoperative or
      intensive care unit patients with a low pulmonary reserve should receive
      infusions of medium-chain triglycerides over a more prolonged period than long
      chain triglycerides.

PMID- 8306685
TI  - Fiberoptic bronchoscopy in the intensive care unit--a prospective study of 147
      procedures in 107 patients.
AB  - OBJECTIVE: To determine the value and safety of fiberoptic bronchoscopy in an
      intensive care unit (ICU). DESIGN: Prospective survey. SETTING: ICUs at a
      tertiary care hospital (except for seven procedures that were performed at a
      peripheral hospital ICU). PATIENTS: A total of 107 patients with a mean age of
      43.9 yrs (range 15 to 84). INTERVENTIONS: One hundred forty-seven fiberoptic
      bronchoscopy procedures (116 performed on patients who were undergoing mechanical
      ventilation) were performed on 107 patients. Ninety-four procedures were for
      diagnostic reasons (upper and lower airway inspection, focal and diffuse
      pulmonary infiltrates), 37 for therapeutic reasons (bronchial toilet, pulmonary
      hemorrhage, endotracheal intubation), and 16 for both reasons. Topical
      anaesthesia was used for fiberoptic bronchoscopy; sedation was rarely needed.
      Appropriate diagnostic and therapeutic procedures were performed. MEASUREMENTS
      AND MAIN RESULTS: Oxygen saturation, electrocardiogram, and blood pressure were
      monitored. Transbronchial biopsies (all on mechanical ventilation) for diffuse
      pulmonary infiltrates were diagnostic in five of seven cases, and were suggestive
      of the diagnosis in a further case. Endobronchial biopsies were not diagnostic in
      any of three cases. Bronchial brushings for microbiology were positive in nine of
      50 procedures and for cytology in one of nine procedures. Protected specimen
      brushes for pulmonary infiltrates gave positive microbiology findings in five of
      23 procedures. In pulmonary hemorrhage, focal bleeding was found in five cases,
      diffuse bleeding in four, and no bleeding source in three. In lobar atelectasis,
      bronchial toilet led to full reexpansion (n = 20 procedures), partial reexpansion
      (n = 5), and no change (n = 3). Intubation with fiberoptic bronchoscopy was
      successful in four of five patients. Hypoxemia (oxygen saturation < 90%) occurred
      in 29 procedures; it caused no problems. Complications included hemorrhage (n =
      2), supraventricular tachycardia (n = 1), pneumothorax (n = 1), pneumatocele (n =
      1), and bronchospasm (n = 1). No deaths were attributable to fiberoptic
      bronchoscopy. CONCLUSIONS: Fiberoptic bronchoscopy in the ICU is safe,
      contributes valuable diagnostic information, and is useful for therapeutic
      purposes.

PMID- 8306686
TI  - Role of early enteral feeding and acute starvation on postburn bacterial
      translocation and host defense: prospective, randomized trials.
AB  - OBJECTIVES: To investigate the effect of: a) starvation during the preburn period
      and b) immediate postburn enteral nutrition on the permeability of the gut to
      microorganisms and the ability of the host to kill translocated bacteria. DESIGN:
      Prospective, randomized, experimental trials. SETTING: Laboratory. SUBJECTS:
      Balb/c mice and Hartley guinea pigs. INTERVENTIONS: In the first experiment, mice
      were starved for 0, 6, 12, 18, or 24 hrs before receiving gavage with 10(10) 14C
      labeled Escherichia coli and a 20% burn injury. In the second experiment, guinea
      pigs received a 40% burn injury and were randomized to receive a complete enteral
      diet (175 kcal/kg/day) or infusion of an equal volume of lactated Ringer's
      solution via a previously placed gastrostomy for 6, 24, or 48 hrs. After each
      feeding period, 10(10) 14C Escherichia coli were infused intragastrically. In
      both experiments, the animals were killed 4 hrs after gavage, and mesenteric
      lymph nodes, spleen, liver, lungs, peritoneal fluid, and blood were harvested
      aseptically. MEASUREMENTS: For each tissue or fluid, the number of viable E. coli
      and radionuclide counts of the 14C E. coli were measured and the percentage of
      translocated bacteria that remained alive was calculated. MAIN RESULTS: In mice,
      18 and 24 hrs of preburn starvation increased translocation only to the
      mesenteric lymph nodes, but it also enhanced bacterial killing in all tested
      tissues. Guinea pigs that were fed enterally for 6, 24, and 48 hrs postburn had
      significantly lower bacterial translocation in all tissues compared with animals
      infused with lactated Ringer's solution. Additionally, enhanced killing of
      translocating organisms was observed after 24 and 48 hrs of feeding. CONCLUSIONS:
      Starvation preburn has different consequences than starvation postburn on
      translocation and bacterial killing. Postburn enteral nutrition decreases the
      load of viable bacteria in the tissues via a double mechanism: an initial
      decreased translocation and a subsequent improved ability to kill bacteria that
      do translocate.

PMID- 8306687
TI  - Effects of pentoxifylline on cerebral blood flow, metabolism, and evoked response
      after total cerebral ischemia in dogs.
AB  - OBJECTIVE: To test the hypothesis that pentoxifylline improves recovery of
      cerebral electrical activity and metabolic function after a transient cerebral
      global ischemia by improving cerebral blood flow during the reperfusion period.
      DESIGN: Randomized, controlled, prospective study. SETTING: University research
      laboratory. SUBJECTS: Forty male beagle dogs. INTERVENTIONS: Six control dogs
      received pentoxifylline (40 mg/kg bolus followed by infusion at 0.2 mg/kg/hr)
      without ischemia. Thirteen dogs received Ringer's lactate solution with 12 mins
      of cerebral global ischemia (by aortic occlusion). Nine dogs received
      pentoxifylline before ischemic insult. Six dogs received pentoxifylline on
      reperfusion, and six dogs received pentoxifylline 30 mins after reperfusion.
      MEASUREMENTS AND MAIN RESULTS: Total and regional cerebral blood flow, cerebral
      oxygen consumption, and somatosensory evoked potentials were measured during 180
      mins of reperfusion. Pentoxifylline did not affect cerebral blood flow, oxygen
      consumption, or somatosensory evoked potentials without ischemia. Pretreatment
      with pentoxifylline resulted in attenuated postischemic hyperemia at 10 mins of
      reperfusion (94 +/- 15 vs. 133 +/- 11 [SEM] mL/min/100 g; p < .05), but there was
      no difference in total cerebral blood flow or oxygen consumption during later
      points of reperfusion. Pentoxifylline treatment during reperfusion resulted in no
      recovery of cerebral blood flow or oxygen consumption. All ischemic groups
      demonstrated a rapid ablation of somatosensory evoked potential amplitude and
      there were no differences in the decrement of the amplitude on ischemia. At 180
      mins of reperfusion, somatosensory evoked potentials recovered to the following
      percentages of the baseline control values: 28 +/- 4% in dogs treated with
      Ringer's lactate solution; 58 +/- 4% in the pentoxifylline pretreated group (p <
      .05); 40 +/- 5% in dogs receiving pentoxifylline at reperfusion (p > .05); and 53
      +/- 8% in dogs receiving pentoxifylline at 30 mins of reperfusion (p < .05).
      CONCLUSIONS: Pentoxifylline treatment improves recovery of cerebral electrical
      function after complete transient cerebral global ischemia by a mechanism that
      does not involve improvement in cerebral blood flow or global oxygen consumption.

PMID- 8306689
TI  - Cerebrovascular response to carbon dioxide in lambs receiving extracorporeal
      membrane oxygenation.
AB  - OBJECTIVE: To determine if the institution of extracorporeal membrane oxygenation
      (ECMO) alters the cerebrovascular response to changes in PaCO2. DESIGN:
      Prospective, randomized, controlled animal trial. SUBJECTS: Anesthetized 1- to 7
      day-old lambs of mixed breed (n = 16). SETTING: University research laboratory.
      INTERVENTIONS: The experimental group was placed on ECMO. Both experimental and
      control groups (n = 8) were exposed to three concentrations of PaCO2 (hypocarbia,
      normocarbia, and hypercarbia) by varying mechanical ventilation and by adding
      carbon dioxide to the ventilator gases. MEASUREMENTS AND MAIN RESULTS: Cerebral
      blood flow was measured by the radiolabeled microsphere method. Arterial blood
      gases and sagittal sinus blood gases were drawn at the time of cerebral blood
      flow measurement so that cerebral metabolism, cerebral oxygen transport, and
      extraction could be calculated. In the control group, as PaCO2 increased from 34
      +/- 2 (SD) to 53 +/- 4 torr (4.5 +/- 0.3 to 7.1 +/- 0.5 kPa), cerebral blood flow
      increased from 53 +/- 12 to 147 +/- 50 mL/min/100 g. This increase in cerebral
      blood flow was not different from that of the ECMO group, where PaCO2 increased
      from 33 +/- 2 to 56 +/- 3 torr (4.4 +/- 0.3 to 7.5 +/- 0.4 kPa) and cerebral
      blood flow increased from 48 +/- 17 to 106 +/- 38 mL/min/100 g. As PaCO2
      decreased from 34 +/- 2 to 19 +/- 2 torr (4.5 +/- 0.27 to 2.5 +/- 0.27 kPa),
      cerebral blood flow decreased from 53 +/- 12 to 43 +/- 8 mL/min/100 g in the
      control group. This decrease was not different from that of the ECMO group, where
      cerebral blood flow decreased from 48 +/- 17 to 39 +/- 10 mL/min/100 g as PaCO2
      decreased from 33 +/- 2 to 22 +/- 3 torr (4.4 +/- 0.3 to 2.9 +/- 0.4 kPa). When
      regional cerebral blood flow was analyzed, no regional differences in the
      cerebrovascular responses to PaCO2 between ECMO and control groups were found.
      The cerebral metabolic rate was not different between ECMO and control groups at
      any level of PaCO2, nor was the cerebral metabolic rate affected by changes in
      PaCO2. Oxygen extraction increased with hypocarbia and decreased with hypercarbia
      in a similar fashion in both ECMO and control groups. CONCLUSION: The
      cerebrovascular response to changes in PaCO2 was unaffected by ECMO.

PMID- 8306688
TI  - High-dose epinephrine results in greater early mortality after resuscitation from
      prolonged cardiac arrest in pigs: a prospective, randomized study.
AB  - OBJECTIVE: To determine whether high-dose epinephrine (0.2 mg/kg) during
      cardiopulmonary resuscitation (CPR) results in improved outcome, compared with
      standard-dose epinephrine (0.02 mg/kg). DESIGN: A prospective, randomized,
      blinded study. SETTING: Research laboratory of a university medical center.
      SUBJECTS AND INTERVENTIONS: Thirty domestic swine were randomized to receive
      standard- or high-dose epinephrine during CPR after 15 mins of fibrillatory
      cardiac arrest. Three minutes of CPR were provided, followed by advanced cardiac
      life support per American Heart Association guidelines. Animals that were
      successfully resuscitated were supported for 2 hrs in an intensive care unit
      (ICU) setting, and then observed for 24 hrs. MEASUREMENTS AND MAIN RESULTS:
      Electrocardiogram, aortic blood pressure, right atrial blood pressure, and end
      tidal CO2 were monitored continuously until the intensive care period ended.
      Survival and neurologic outcome were determined. Return of spontaneous
      circulation was attained in 14 of 15 animals in each group. Four of 14 high-dose
      epinephrine pigs died during the ICU period after return of spontaneous
      circulation vs. zero of the 14 standard-dose pigs (p < .05). Six standard-dose
      pigs survived 24 hrs vs. four high-dose pigs. Twenty-four-hour survival rate and
      neurologic outcome were not significantly different. Within 10 mins of
      defibrillation, severe hypertension (diastolic pressure > 120 mmHg) occurred in
      12 of 14 high-dose pigs vs. two of 14 standard-dose pigs (p < .01). Severe
      tachycardia (heart rate > 250 beats/min) occurred in seven of 14 high-dose pigs
      vs. zero of 14 standard-dose pigs (p < .01). All four high-dose epinephrine pigs
      that died during the ICU period experienced both severe hypertension and
      tachycardia immediately postresuscitation. CONCLUSIONS: High-dose epinephrine did
      not improve 24-hr survival rate or neurologic outcome. Immediately after return
      of spontaneous circulation, most animals in the high-dose epinephrine group
      exhibited a hyperadrenergic state that included severe hypertension and
      tachycardia. High-dose epinephrine resulted in a greater early mortality rate.

PMID- 8306690
TI  - Effects of dobutamine and norepinephrine on oxygen availability in tamponade
      induced stagnant hypoxia: a prospective, randomized, controlled study.
AB  - OBJECTIVES: To explore the effects of dobutamine and norepinephrine on the global
      cardiovascular response and on the relationship between oxygen uptake (VO2) and
      oxygen delivery (DO2) during an acute reduction in blood flow associated with
      tamponade. DESIGN: Prospective, randomized, controlled acute intervention study.
      SETTING: University intensive care unit (ICU) laboratory. SUBJECTS: Twenty
      healthy, anesthetized mongrel dogs, weighing 19 to 28 kg. INTERVENTIONS: Six dogs
      served as control, seven dogs were given 10 micrograms/kg/min of dobutamine and
      another seven dogs were given 1 microgram/kg/min of norepinephrine. Data were
      collected at graded incremental levels of intrapericardial pressure. MEASUREMENTS
      AND MAIN RESULTS: VO2 was derived from expired gas analysis and DO2 was
      calculated from the product of thermodilution cardiac index and arterial oxygen
      content. In each animal, two catheters were inserted into the pericardium to
      induce tamponade by saline infusion and to measure the intrapericardial pressure.
      The critical Do2 value, below which VO2 decreased, was found at 9.4 +/- 1.3
      mL/kg/min in the control animals. When DO2 decreased to below this critical
      value, lactic acidosis developed. Dobutamine and norepinephrine, at the dose that
      was administered, significantly increased cardiac index and DO2. Critical DO2 was
      slightly higher in the treated than in the control animals (12.1 +/- 1.6
      mL/kg/min in dobutamine and 13.2 +/- 0.9 mL/kg/min in norepinephrine, NS). VO2 at
      critical DO2 was significantly higher in the treated groups than in the control
      group (7.7 +/- 1.1 mL/kg/min in the dobutamine group and 7.9 +/- 0.9 mL/kg/min in
      the norepinephrine group vs. 5.4 +/- 0.4 mL/kg/min in control, both p < .01).
      There was no significant difference in the critical oxygen extraction ratio and
      the slope of the supply-dependent line between the three groups. In dobutamine
      treated animals, cardiac index, DO2, and VO2 were better maintained for any
      intrapericardial pressure than in the other groups. Critical intrapericardial
      pressure, at which VO2 started to decrease, was significantly higher in the
      dobutamine-treated group than in the control group (13.8 +/- 2.3 vs. 9.3 +/- 1.2
      mm Hg, p < .05). At critical DO2, the mean blood lactate concentration was also
      lower in the dobutamine-treated animals than in the other animals (2.1 +/- 0.3
      vs. 4.1 +/- 0.7 mmol/L in control and 3.8 +/- 0.4 mmol/L in the norepinephrine
      group, both p < .05). CONCLUSIONS: During low-flow states associated with
      tamponade, both dobutamine and norepinephrine at the dose used increased cardiac
      index, DO2, and VO2, but dobutamine delayed the onset of tissue hypoxia by
      further increasing blood flow and oxygen availability. In the conditions of the
      present study, neither agent significantly influenced the oxygen extraction
      capabilities of the body.

PMID- 8306692
TI  - Functional characteristics of pediatric veno-venous hemofiltration.
AB  - OBJECTIVE: To evaluate the functional characteristics of continuous veno-venous
      hemofiltration in a pediatric size animal model. DESIGN: Prospective trial.
      SETTING: Animal laboratory at a large university-affiliated medical center.
      SUBJECTS: Four-week old lambs (weight 12.2 +/- 1.3 kg). INTERVENTIONS: Veno
      venous hemofiltration was performed in anesthetized lambs (n = 5, 12.2 +/- 1.3
      kg) using a standard pediatric hemofilter and pumped blood and ultrafiltrate. We
      compared postdilution, predilution, and hemofiltration with counterflow dialysis.
      MEASUREMENTS AND MAIN RESULTS: At net ultrafiltrate flows of 200, 400, and 600
      mL/hr, we measured system pressures and urea clearance. Stable blood flow could
      reproducibly be achieved up to 140 mL/min (10 mL/kg/min); at higher flow demand,
      tubing collapse occurred. At blood flow rates of 5 to 10 mL/kg/min, ultrafiltrate
      flow of 1 mL/kg/min would create negative filter compartment pressure but
      consistently less negative than -500 mm Hg. During postdilution, predilution, and
      counterflow dialysis, urea clearance was virtually equal to ultrafiltrate flow.
      There was no increase in urea clearance when adding predilution or dialysis to
      basic postdilution. CONCLUSIONS: Veno-venous hemofiltration, using small filters
      and circuits in a pediatric size animal, can achieve stable blood flow up to 10
      mL/kg/min. At this flow, ultrafiltrate flow of 1 mL/kg/min can produce a urea
      clearance of 1 mL/kg/min while keeping filter compartment pressure above maximal
      recommended negative pressures. Addition of dialysis in this nonuremic model did
      not increase urea clearance.

PMID- 8306691
TI  - Effects of nitric oxide synthesis inhibition in hyperdynamic endotoxemia.
AB  - OBJECTIVE: To investigate the effects of N omega-nitro-L-arginine methyl ester,
      an inhibitor of nitric oxide synthesis, on hemodynamics, gas exchange and oxygen
      transport in an ovine model of hyperdynamic sepsis. DESIGN: Prospective,
      nonrandomized, controlled study, with repeated measurements. SETTING: University
      research laboratory. SUBJECTS: Twenty healthy adult sheep (weighing 20 to 45 kg)
      were divided into two groups of 12 treated sheep and eight control sheep and
      studied. INTERVENTIONS: Twenty awake, chronically instrumented sheep received a
      continuous infusion of endotoxin (10 ng/kg/min) over 48 hrs. Twenty-four hours
      after the start of the endotoxin infusion, 12 sheep (treatment group) received a
      bolus of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl
      ester (25 mg/kg), while the other eight animals (control group) received the
      carrier (0.9% NaCl). MEASUREMENTS AND MAIN RESULTS: Twenty-four hours after the
      start of the endotoxin infusion, both groups exhibited a hyperdynamic state with
      increased cardiac indices, decreased systemic vascular resistance indices,
      impaired oxygenation, and increased pulmonary shunt fractions. In both groups,
      oxygen delivery was significantly increased, while oxygen consumption remained
      virtually unchanged, resulting in a decreased oxygen extraction ratio. In the
      control group, the significant alterations in systemic hemodynamics, lung
      function and oxygen transport persisted for the remainder of the study.
      Administration of N omega-nitro-L-arginine methyl ester normalized cardiac index
      and systemic vascular resistance index, increased mean arterial blood pressure,
      and decreased heart rate. Although oxygen delivery significantly decreased after
      administration of N omega-nitro-L-arginine methyl ester, oxygen consumption did
      not change, resulting in a normalization of oxygen extraction ratio. Despite a
      significant reduction of pulmonary shunt fraction, oxygenation did not improve.
      Pulmonary arterial pressure and pulmonary vascular resistance index showed a peak
      2 hrs after administration of the nitric oxide synthesis inhibitor and then
      tended to decrease. In contrast, the effects of N omega-nitro-L-arginine methyl
      ester on the systemic circulation persisted for the remainder of the study.
      CONCLUSIONS: The data support the assumption that augmented nitric oxide
      production is a major cause of the hemodynamic alterations seen in hyperdynamic
      endotoxemia. Administration of the nitric oxide synthesis inhibitor N omega-nitro
      L-arginine methyl ester normalized the endotoxin-induced hyperdynamic state, but
      did not impair oxygen consumption, indicating adequate tissue perfusion of
      metabolically active organs. Inhibition of nitric oxide synthesis may be a
      therapeutic option in the treatment of hyperdynamic septic patients when
      conventional therapy fails to maintain a minimum of cardiovascular performance.

PMID- 8306693
TI  - A pressurized injection/suction system for ventilation in the presence of
      complete airway obstruction.
AB  - OBJECTIVE: To describe the design and ventilatory characteristics of a new mode
      of ventilation (pressurized injection/suction ventilation). DESIGN: Descriptive
      and analytical laboratory study. SETTING: Laboratory study. SUBJECTS: Simulated
      lung model and dogs. INTERVENTIONS: We tested the ability to maintain ventilation
      through a 2.5-mm internal diameter ventilating stylet in the setting of simulated
      complete airway occlusion. A microprocessor-controlled ventilator mode was used
      wherein injection of oxygen under high pressure (flow rate 95 L/min) alternates
      with suction of expired gas (flow rate 18 L/min) through the ventilating stylet.
      MEASUREMENTS AND MAIN RESULTS: In a lung model, we achieved a maximum minute
      ventilation of 12.9 L/min. In two dogs, we maintained stable oxygenation (mean
      PaO2 603 +/- 47 torr [80.4 +/- 6.3 kPa]) and ventilation (mean PaCO2 19 +/- 3
      torr [2.5 +/- 0.4 kPa]) for 15 mins at maximum minute ventilation settings. No
      clinically important deleterious effects on the tracheal mucosa were observed.
      The ventilator system's safety-abort feature prevented overinflation or excessive
      deflation of the dogs' lungs in every test of simulated malfunction of the
      pressure-monitoring mechanism. CONCLUSIONS: Pressurized injection/suction
      ventilation can maintain adequate gas exchange in an animal model with near
      complete airway obstruction. Further work is needed to develop the safety and
      clinical applications of pressurized injection/suction ventilation in the
      management of patients with near-complete airway occlusion.

PMID- 8306694
TI  - Opioid tolerance and dependence in infants and children.
AB  - OBJECTIVES: To review the definitions and scientific basis for opioid tolerance
      and dependence in neonates and older children; to assess objective methods for
      the clinical evaluation of opioid abstinence syndromes in this age group; and to
      suggest therapeutic strategies for the treatment of opioid abstinence in
      critically ill neonates and children. DATA SOURCES: The published literature on
      opioid tolerance and dependence in pediatric patients was reviewed. Data from
      current clinical practices, nursing procedures, and ongoing clinical research
      were evaluated. DATA SYNTHESIS: Currently proposed mechanisms of opioid tolerance
      and dependence are assessed, with particular relevance to the developing human
      central nervous system. The validity and clinical role of currently available
      objective methods for the assessment of opioid abstinence in neonates and older
      infants are defined. The efficacy of various pharmacologic and nonpharmacologic
      modalities for the treatment of opioid abstinence is evaluated and compared, and
      a therapeutic approach based on receptor mechanisms, clinical monitoring data,
      and pharmacologic efficacy is suggested. CONCLUSIONS: Important parallels for
      therapeutically-induced opioid tolerance and withdrawal may be drawn from the
      assessment and management of neonates born from opioid-addicted mothers. Opioid
      withdrawal can be prevented with appropriate weaning schedules, diagnosed by
      objective clinical methods, and treated by a variety of pharmacologic and non
      pharmacologic means. Pharmacologic therapy includes the use of opioids, with
      adjuvant drugs such as diazepam, clonidine, or chlorpromazine. The
      pathophysiology and assessment of therapeutically induced opioid tolerance and
      withdrawal merit further research in critically ill pediatric patients.

PMID- 8306695
TI  - Mixed venous oxygenation in critically ill neonates.
AB  - OBJECTIVE: To describe the typical ranges for central venous oxygen saturation
      and PO2 in a group of critically ill neonates and the relationship of these
      measurements to measurements of arterial oxygenation and indicators of oxygen
      supply and demand. DESIGN: Survey. SETTING: Newborn intensive care unit (ICU) in
      a children's hospital. PATIENTS: Eighteen newborn infants (1 to 3 days old) who
      required mechanical ventilation for respiratory diseases, but who were
      hemodynamically stable and in acid-base balance. INTERVENTIONS: Umbilical artery
      and right atrial catheterization were performed, allowing simultaneous blood gas
      sampling. MEASUREMENTS AND MAIN RESULTS: Simultaneous umbilical arterial and
      right atrial blood gas measurements were analyzed (n = 100). Mean mixed venous
      oxygen saturation was 83.3% and mixed venous oxygen tension 37.8 torr (5.1 kPa).
      The mixed venous oxygen saturation correlated well with the arterial-venous
      oxygen content difference (C[a-v]O2) and fractional oxygen extraction, r = -.77
      (r2 = .59) and -.85 (r2 = .72), respectively (p < .0005). Poor correlation was
      found between the mixed venous oxygen saturation and arterial oxygen saturation
      values. Two cases are presented in which measurements of mixed venous oxygenation
      led to recognition of apparent tissue hypoxia earlier than did measurements of
      arterial oxygenation. CONCLUSIONS: We conclude that measurement of central venous
      oxygenation in ill neonates may reflect more accurately the oxygen supply and
      demand status of the neonate than measurement of arterial oxygenation alone.

PMID- 8306696
TI  - Use of the Hickman-Crawford critical care catheter in marrow transplant
      recipients: a pulmonary artery catheter-adaptable central venous access.
AB  - OBJECTIVE: To describe the use of a modified 15.5-Fr double-lumen, tunneled right
      atrial catheter (Hickman-Crawford catheter) in adult bone marrow transplant
      recipients, that permits passage of a 5-Fr pulmonary artery catheter through the
      larger of the catheter's lumens. DESIGN: A case series review of the clinical
      experience with a modification of the existing central venous catheter design.
      SETTING: A bone marrow transplantation center. PATIENTS: Fourteen patients
      (weighing at least 50 kg body weight) undergoing bone marrow transplantation.
      Ages ranged from 18 to 64 yrs (median 40). There were nine male and five female
      patients. All patients, except for three who were receiving autologous marrow
      transplants, underwent allogeneic transplants. MEASUREMENTS AND MAIN RESULTS:
      Sixteen catheters were inserted into the subclavian vein in 14 patients. The
      catheters remained in place for a mean of 44 days (median 30; range 6 to 107) and
      56% remained functional until removed an average of 60 days later at the time of
      death (n = 5) or discharge to home (n = 4). One catheter was accidentally
      dislodged by the patient and six catheters (38%) were electively removed, two
      because of infection and four because of mechanical occlusion or damage. The
      Hickman-Crawford catheter was used as venous access for insertion of 21 pulmonary
      artery catheters in 12 patients (twice in seven patients). Ninety percent of
      these insertions (19 of 21) were done without difficulty; use of a guidewire was
      required in the remaining two cases. No complications of pulmonary artery
      catheterization were seen. CONCLUSIONS: This experience illustrates that a
      tunneled right atrial catheter for long-term use can be employed safely and
      repeatedly for insertion of pulmonary artery catheters for central hemodynamic
      monitoring.

PMID- 8306697
TI  - Combining pressure-limiting and volume-cycling features in a patient-interactive
      mechanical breath.
AB  - OBJECTIVES: To combine the patient synchrony effects of pressure-limited breath
      delivery strategies with the volume guarantee of volume-cycled breath delivery
      strategies, we designed a positive-pressure breath that incorporates both
      features. This breath is patient triggered and can be pressure limited. Breath
      termination (i.e., cycling) can either be flow- or volume-cycled, depending on
      whether a target volume has been attained. The pressure-limiting features are
      further enhanced by the capability to adjust demand-valve responsiveness at
      breath initiation. DESIGN: Prospective, mechanical simulation studies. SETTING:
      Engineering laboratory. INTERVENTIONS: A mechanical lung model that could
      simulate patient ventilatory efforts was used. Vigorous and weak patient efforts
      were studied in conjunction with use of volume assist, pressure support, and a
      combination pressure-limited and volume-cycled breath. MEASUREMENTS AND MAIN
      RESULTS: Two clinical situations were simulated by the model: a) a patient
      requiring total mechanical ventilatory support who had a very active ventilatory
      drive; and b) a patient receiving only partial ventilatory support who had an
      unstable ventilatory drive. A range of pressure-limiting and volume-cycling
      settings were given. Volume, pressure, and flow delivery were measured. Synchrony
      with patient effort was assessed by visual inspection of airway pressure graphics
      as well as by calculations of patient work during these support strategies.
      CONCLUSIONS: Flow dyssynchrony during fixed-flow, volume-cycled assisted breaths
      in patients with active ventilatory drives can be improved with this breath
      design while a guaranteed tidal volume is maintained. In addition, this
      combination breath can provide a volume "safety net" for patients in whom partial
      support with pressure-support ventilation is desired.

PMID- 8306698
TI  - Attitudes of critical care medicine professionals concerning distribution of
      intensive care resources. The Society of Critical Care Medicine Ethics Committee.
AB  - OBJECTIVE: To determine critical care practitioners' attitudes about the
      importance of various factors in decisions to use intensive care, including age,
      prognosis, quality of life, patient preference, and medical condition. DESIGN:
      Cohort study. SETTING: The Annual Educational and Scientific Symposium of the
      Society of Critical Care Medicine. SUBJECTS: Participants at the symposium.
      RESULTS: A self-administered questionnaire was distributed and 600 (52%) of 1,148
      registrants attending the symposium responded. Eighty-four percent of respondents
      were physicians and 11% were nurses. Physicians were internists (30%), surgeons
      (24%), pediatricians (22%), and anesthesiologists (19%); 58% were in academic
      practices. Very few respondents believed that age should be a criterion for
      limiting intensive care (12%). Quality of life as viewed by the patient,
      probability of surviving hospitalization, reversibility of the acute disorder,
      and nature of the chronic disorder were the factors that most respondents
      considered to be important in decisions to admit to the intensive care unit. The
      patient's social worth, previous psychiatric history, cost-benefit analysis, and
      cost to society were the factors most respondents considered of little
      importance. Over 40% of respondents would admit patients with a chronic
      vegetative state or a patient with metastatic carcinoma and a superimposed, life
      threatening event. CONCLUSIONS: These results suggest that critical care
      providers, who must occasionally face difficult decisions about how to distribute
      limited resources among patients with competing needs, were not often inclined,
      at the time of this survey, to make choices based on estimates of who might
      benefit most. These critical care physicians' attitudes about triage may not
      support the optimal use of critical care resources.

PMID- 8306699
TI  - Low-dose ornipressin improves renal function in the hepatorenal syndrome.

PMID- 8306700
TI  - Nonatherosclerotic myocardial infarction: a rare thromboembolic complication of
      craniotomy.

PMID- 8306701
TI  - Oral ranitidine for gastric stress ulcer prophylaxis intensive care unit
      patients.

PMID- 8306702
TI  - Asymptomatic hypomagnesemia.

PMID- 8306703
TI  - Control of intracellular pH in mammalian liver at hypothermia: evidence for a
      relationship with energy metabolism.
AB  - The metabolic status of rat livers during hypothermia has been studied using 31P
      magnetic resonance spectroscopy. Perfusion with oxygenated buffer at 6-8 degrees
      C allowed maintenance of ATP, while pH increased to values in the range 7.7-7.9.
      In organs depleted of ATP by a short (2 h) period of cold ischemia, pH fell to
      6.92 +/- 0.10. If these livers were reperfused with hypoxic buffer at
      hypothermia, two distinct responses were noted. In one group (responders), there
      was evidence of ATP resynthesis and in these organs pH returned to 7.90 +/- 0.28.
      In the second group (non-responders), there was no recovery of ATP synthesis and
      pH remained depressed at 6.97 +/- 0.07. In another group, adenine nucleotides
      were severely depleted by 24 h of cold ischemia, and in these livers there was
      again no significant recovery of ATP synthesis during hypoxic reperfusion and pH
      remained at 7.03 +/- 0.25. These results suggest that (a) there is an apparent
      relationship between energy metabolism and control of intracellular pH in the
      hypothermic mammalian liver, and (b) that intracellular pH may shift in liver at
      hypothermia to values predicted by the alpha-stat hypothesis.

PMID- 8306704
TI  - 31P NMR studies of rat liver cold preservation with histidine-buffered
      lactobionate solution.
AB  - The efficiency of a preservation medium, histidine-buffered lactobionate solution
      (HBLS), was determined by measuring post-ischemic recoveries of ATP and
      intracellular pH under Krebs-Henseleit buffer (KHB) perfusion. We used NMR
      spectroscopy to study the effect of 24-h cold ischemia, followed by 4 degrees C
      then 37 degrees C reperfusion on the isolated rat liver. Three media were
      compared: University of Wisconsin solution (UW-lactobionate); Bretschneider's
      solution (HTK); HBLS and HBLS supplemented with 2 mM Gly and 2 mM Cys (HBLSg2) or
      with 10 mM Gly and 2 mM Cys (HBLSg10). All values were compared to control values
      measured during pre-ischemic cold perfusion with KHB (ATP = 8.60 +/- 0.6 mumol/g
      of dry weigh and pH(in) = 7.41 +/- 0.05). The main result from 31P NMR data
      concerned ATP recovery during cold reperfusion, which was significantly higher in
      the HBLS group (112 +/- 10%) as compared to the UW and HTK groups (around 66%).
      The presence of glycine decreased ATP recovery (88 +/- 8% in HBLSg2, 79 +/- 15%
      in HBLSg10). Higher values of recovered pHin were observed in livers stored in
      histidine buffered solutions (around 7.30) as compared to UW (around 7.20);
      histidine was by 13C NMR proved to accumulate in the liver cells, thus ensuring a
      good buffering capacity. The thermal transition induced a decrease in both ATP
      level and pHin in all groups. This might be the result of a stimulation of the
      carbohydrate metabolism (as demonstrated by 13C NMR) especially when glycine was
      present in the storage solution.

PMID- 8306705
TI  - Osmometric behavior, hydraulic conductivity, and incidence of intracellular ice
      formation in bovine oocytes at different developmental stages.
AB  - Bovine oocytes that were immature (IMM), matured in vitro (IVM) or in vivo (MAT),
      or matured and fertilized in vitro (IVF) were studied using a microscope
      diffusion chamber to estimate osmotic parameters and a cryomicroscope to
      characterize intracellular ice formation (IIF). Linear Boyle van't Hoff
      relationships were observed with all four types of oocytes between 0.265 and
      0.799 osm NaCl. At 20 degrees C, estimates of hydraulic conductivity (Lp) were
      significantly higher for IVM oocytes than IMM and MAT oocytes (0.84
      micron/(min.atm) vs 0.45 and 0.47, respectively). IVM oocytes also tended to have
      higher Lp values than IVF oocytes (0.55 micron/(min.atm)). At 5 degrees C, the Lp
      of IVM oocytes decreased to 0.36 micron/min.atm) corresponding to an Arrhenius
      activation energy of 7.84 kcal/mol. The incidence of IIF in MAT oocytes suspended
      in salt solution and subjected to linear cooling to -60 degrees C was 45% at 4
      degrees C/min, 75% at 8 degrees C/min, and 93% at 16 degrees C/min; with IVF
      oocytes, the incidence of IIF was 40% at 4 degrees C/min, 92% at 8 degrees C/min,
      and 100% at 16 degrees C/min. Comparisons involving median IIF temperatures
      (TIIF50s) and the distributions of the observed IIF temperatures for IMM (Myers
      et al., Cryo-Lett. 8, 260), IVM (Chandrasekaran et al., Cryobiology 27, 676), MAT
      and IVF oocytes indicated that the IIF incidence in IMM oocytes cooled at 4
      degrees C/min was greater than that of oocytes at the other developmental stages
      cooled at the same rate. The TIIF50s of IVM and IVF oocytes were lowered by
      equilibration in 1.5 M ethylene glycol (EG), glycerol, or propylene glycol (PG)
      prior to cooling, with EG tending to lower the TIIF50s more than glycerol or PG.
      For all three cryoprotectants, the TIIF50s and IFF temperature distributions were
      cooling-rate dependent. The Weibull probability distribution was fitted to the
      distributions of the IIF temperatures of oocytes suspended in salt solutions with
      and without cryoprotectants yielding R2 values ranging from 0.70 to 0.98.

PMID- 8306706
TI  - Protective role of trehalose during heat stress in Saccharomyces cerevisiae.
AB  - Yeast cells accumulate the disaccharide trehalose in response to certain stress
      conditions. In an attempt to verify the role that trehalose plays when yeast
      cells are faced with heat stress, yeast mutant strains with specific lesions in
      trehalose metabolism were used. Cultures growing exponentially on glucose were
      shifted from 28 to 40 degrees C for 1 h. Accumulation of trehalose was correlated
      with heat tolerance, measured as resistance to 50.5 degrees C. Additionally, it
      was observed that the trehalose carrier was not involved in the mechanism of
      thermotolerance acquisition. Mutants that lack the carrier were also able to
      acquire thermotolerance as long as synthesis of the disaccharide took place.

PMID- 8306707
TI  - Large ice crystals in the nucleus of rapidly frozen liver cells.
AB  - Evidence in the literature shows that ice crystals that form in the nucleus of
      many rapidly cooled cells appear much larger than the ice crystals that form in
      the surrounding cytoplasm. We investigated the phenomenon in our laboratory using
      the techniques of freeze substitution and low temperature scanning electron
      microscopy on liver tissue frozen by liquid nitrogen plunge freezing. This method
      is estimated to cool the tissue at 1000 degrees C/min. The results from these
      techniques show that the ice crystal sizes were statistically significantly
      larger in the nucleus than in the cytoplasm. It is our belief that this finding
      is important to cryobiology considering its potential role in the process of
      freezing and the mechanisms of damage during freezing of cells and tissues.

PMID- 8306708
TI  - Development of whole and demi-embryos of mice in culture and in vivo after
      supercooled storage.
AB  - Demi-embryos (produced by destroying 1 or 2 blastomeres of 2- or 4-cell embryos,
      respectively) and intact mouse embryos were cultured to the blastocyst stage,
      stored at -5 degrees C for 48 h, then cultured for 24 h and transferred into
      pseudopregnant recipients. Supercooled storage did not impair the developmental
      potential of whole or demi-embryos in vitro, nor was there a difference between
      whole and demi-embryos with respect to growth in vitro. Similarly, there was no
      effect of supercooling on development of intact or demi embryos after transfer
      into pseudopregnant recipient mice, but fewer recipients of demi-embryos remained
      pregnant (P < 0.05). This was considered to be partly due to the lesser ability
      of demi-embryos to maintain luteal function and establish pregnancy.

PMID- 8306709
TI  - Temporal sequence of changes in tear film composition during sleep.
AB  - Overnight eye closure induces a shift in the nature and composition of the tear
      film, from a dynamic reflex tear-rich to a stagnant secretory IgA-rich layer.
      This is accompanied by the induction of a state of sub-clinical inflammation, as
      evidenced by increases in albumin levels, plasminogen activation, conversion of
      complement C3 to C3c, and the recruitment of polymorphonuclear (PMN) cells into
      the tear film. To determine the time course and functional relationship between
      these potentially interdependent processes, tear samples were collected from ten
      non-contact lens wearers after 1, 2, 3 and 5 hours of sleep. A subgroup of 6
      subjects also self-collected tear samples after 8 hours of sleep. Tear samples
      were analysed for albumin by quantitative immunofixation assay, secretory IgA
      (sIgA) by radial immunodiffusion assay, plasmin-like activity using a chromogenic
      substrate, and complement C3 to C3c conversion by immunoblot assay. Epithelial
      and PMN cells in the precorneal tear film were recovered from corneal washings
      from the same subjects after 1, 3, 5 and 8 hours of sleep, and quantified.
      Results revealed that, unlike epithelial cells which exhibited a slow progressive
      accumulation as a function of the period of sleep, PMN cell concentration
      exhibited a lag phase, with recruitment occurring after between 3 and 5 hours of
      eye closure. This was preceded by plasminogen activation, increases in albumin
      and sIgA levels, and complement C3 to C3c conversion, all of which occurred
      within 1 to 3 hours after eye closure. Plasmin-like activity appeared to plateau
      after 3 hours and then decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306710
TI  - The combined effect of diabetes and ionising radiation on the retinal vasculature
      of the rat.
AB  - The clinical impression that pre-existing diabetes exacerbates radiation injury
      to the retinal vasculature was studied in STZ diabetic rats. Half of 2 groups of
      streptozotocin (STZ)-induced diabetic rats and 1 group of normal animals had
      their right eyes irradiated with 1000 cGy of 90 KVP x-rays. The prevalence of
      acellular capillaries in trypsin digests of the retinal vasculature was
      quantified for each of the 6 groups of animals at 6.5 months post-irradiation.
      The prevalence of acellular capillaries in both non-irradiated diabetic groups
      was significantly higher than in controls while the irradiated animals in each of
      the three main categories showed a statistically significant increase compared to
      their non-irradiated equivalents. However, the net increase in acellular
      capillaries following irradiation was much greater in rats with an 8 month term
      of pre-existing diabetes (180%) than in those which had only been diabetic for 3
      months (36%). The results of this study suggest a synergistic relationship
      between pre-existing diabetes and ionising radiation in the development of
      retinal vasculopathy, and that the potentiation of the vascular damage is
      dependent on the duration of diabetes prior to radiation exposure.

PMID- 8306711
TI  - Three-dimensional visualization of confocal sections of in vivo human fundus and
      optic nerve.
AB  - A confocal scanning laser ophthalmoscope was used to image the human fundus in
      vivo at a series of 32 sections from near the retinal surface to deep within the
      optic nerve head. The optical sections were digitized and aligned to compensate
      for eye movement during image acquisition and stored on a computer. This
      registered stack of optical sections was reconstructed using specialized
      computational software. The three-dimensional volume rendering of the stack of
      optical sections results in a new way to view the in vivo optic nerve in three
      dimensions. This technique is of clinical importance since structural factors of
      the lamina cribrosa of the optic nerve may be important in glaucomatous damage.
      There may be diagnostic potential in the in vivo observation of the three
      dimensional structure of the optic nerve.

PMID- 8306712
TI  - Assignment of tear lipocalin gene to human chromosome 9q34-9qter.
AB  - We assigned the gene for tear lipocalin to the long arm of human chromosome 9.
      Polyadenylated RNA was extracted from lacrimal gland. The coding region for tear
      lipocalin was amplified, sequenced and used to probe a panel of somatic cell
      hybrid DNA by Southern blot analysis. Regional mapping was accomplished by
      probing a panel of subfragments of the indicated chromosome. Restriction of
      genomic DNA with EcoRI failed to reveal any bands corresponding to the human tear
      lipocalin gene in mouse-human hybrids all of which lack chromosome 9. Southern
      blot analysis of human-hamster hybrids demonstrated a human 5.6 kb TaqI
      restriction fragment that segregated to the q34-qter region of chromosome 9 and
      assigned the gene for tear lipocalin to this region. Structurally homologous
      proteins of the lipocalin family, human placental protein 14, human alpha 1
      microglobulin, and human brain prostaglandin synthase, have been mapped to this
      region. We suggest that the gene for tear lipocalin is part of an important
      lipocalin superfamily gene cluster on chromosome 9 within band q34.

PMID- 8306713
TI  - High capacity binding of alpha crystallins to various bovine lens membrane
      preparations.
AB  - This study examines the high capacity binding of intact and carboxyl-terminal
      truncated alpha A(alpha A) crystallin to two types of lens membrane preparations;
      membrane stripped of extrinsic protein and some lipid by extraction with urea and
      alkali and unextracted membrane isolated by centrifugation of total water
      insoluble protein on a sucrose gradient (native membrane). High capacity binding
      of alpha A crystallin to the urea-treated membrane was seen once the alpha A
      substrate concentration reached about 1 mg/ml of media. The membrane bound up to
      one mg of alpha A per mg of intrinsic protein (MP26) at a concentration of 5 mg
      alpha A/ml media, binding 5 to 10 times greater than that seen by others at
      saturation of the high affinity but low capacity binding sites. No apparent
      differences were seen between high capacity binding of carboxyl terminal
      truncated alpha A (by trypsin) and intact alpha A, although each crystalline
      could antagonize binding of the other. However, once membrane bound, neither
      crystallin appeared to grossly displace the other. Using the carboxyl terminal
      truncated alpha crystallin as a model substrate, native membrane was seen to have
      a higher capacity to bind the truncated alpha crystallin than urea-extracted
      membrane and binding was better correlated with the preexisting alpha A content
      of the native membrane than its MP26 content. An artificial native membrane was
      prepared by prebinding the truncated alpha A to urea-extracted membrane. This
      preparation bound more intact alpha A than urea-extracted membrane bearing no
      prebound crystallin. We conclude that lens native membrane possesses a high
      capacity to bind alpha crystallins and that this binding could be mediated
      through protein-protein interactions with alpha crystallin bound in situ to the
      membrane as extrinsic protein.

PMID- 8306714
TI  - Size dependent variation in the fractal dimensions of herpes simplex epithelial
      keratitis.
AB  - Dendritic ulcers, the commonest manifestation of herpes simplex epithelial
      keratitis (HSEK) are fractals. It is likely that their fractal properties alter
      if they progress to a geographic appearance. This study investigates the
      relationship of maximum ulcer diameter (Feret's diameter) to area (Dm) and
      perimeter fractal dimensions (Ds), parameters of the complexity of their areas
      and outlines respectively. For dendritic ulcers in the size range of 1.6-3.2 mm,
      Dm = 1.41 +/- 0.06 and Ds = 1.40 +/- 0.04 (mean +/- SD). With increasing ulcer
      size, a progressive divergence of the values of Dm and Ds occurred, such that
      values of 1.75 and 1.22 respectively were found at a maximum diameter of 8.4 mm.
      These results imply that as ulcers enlarge, their outlines become less irregular
      and they fill more of a 2-dimensional plane. Dm and Ds are useful parameters in
      quantifying the progression of HSEK from dendritic to amoeboid morphology and
      could have a role in the assessment of ulcer response to pharmacological
      intervention. A knowledge of the fractal properties of HSEK may increase
      understanding of the mechanisms of ulcer formation and viral spread.

PMID- 8306715
TI  - Neuromodulatory effect of sulprostone on the circadian elevation of intraocular
      pressure in rabbits.
AB  - Topical application of sulprostone, a preferential prostaglandin EP3 receptor
      agonist, caused a dose-dependent reduction of the circadian elevation of
      intraocular pressure (IOP) in New Zealand albino rabbits which were entrained to
      12-hr/12-hr light-dark environment. Corresponding to the effect on IOP, 0.2
      micrograms, 2 micrograms, and 20 micrograms sulprostone decreased the
      norepinephrine (NE) concentration in the aqueous humor in the dark phase. There
      was no breakdown of the blood-aqueous barrier. Bilateral applications of 2
      micrograms and 20 micrograms sulprostone to entrained rabbits that had undergone
      unilateral, preganglionic transection of the cervical sympathetic trunk reduced
      the circadian IOP elevation in the intact eye, but caused little IOP change in
      the decentralized eye. These results indicate that the IOP-lowering effect of
      topical sulprostone in rabbits is dependent on sympathetic neural activity and
      that prejunctional inhibition of NE release may be an important mechanism of
      action.

PMID- 8306716
TI  - Inositol-1,4,5-trisphosphate receptors in the vertebrate retina.
AB  - Evidence has shown an activation of phosphatidylinositol 4,5-bisphosphate (PIP2)
      specific phospholipase C (PtdIns-PLC) by light in the vertebrate retina and rod
      outer segments (ROS), suggesting important roles for its two metabolites, 1,2
      diacylglycerol (DG) and inositol-1,4,5-trisphosphate [Ins(1,4,5)P3]. DG activates
      protein kinase C (PKC) and Ins(1,4,5)P3 releases bound intracellular calcium.
      Since Ca2+ plays an important role in light adaptation, the presence of
      Ins(1,4,5)P3 receptors in ROS may indicate a regulatory role of Ins(1,4,5)P3 to
      the free Ca2+ content. In the present study, we investigated the Ins(1,4,5)P3
      receptors in whole retinal membranes and several subcellular fractions prepared
      from bovine retinas. Scatchard analyses of binding data for retinal membrane
      preparations showed a single, high-affinity binding site with equilibrium
      dissociation constant (Kd) of 24 +/- 2 nM and maximal binding capacity (Bmax) of
      353 +/- 15 fmol/mg protein at pH 7.4. Specific binding was found in both small
      and large synaptosomal preparations representing inner and outer plexiform
      layers, respectively. A detectable, but low abundance of Ins(1,4,5)P3-specific
      binding in ROS was observed at both pH 7.4 and 8.3, but no specific binding of
      Ins(1,4,5)P3 was found in isolated outer segment discs. The binding of
      Ins(1,4,5)P3 in ROS was reduced by addition of ATP, suggesting a regulatory role
      for this nucleotide. Addition of calcium, sodium, and potassium ions also reduced
      specific binding of Ins(1,4,5)P3. Immunocytochemical studies indicate intense
      staining in the inner segment and extending to the ROS. Inner and outer plexiform
      layers were also stained. These findings show that the Ins(1,4,5)P3 receptor is
      present in photoreceptor cells and inner and outer plexiform layers in the
      vertebrate retina.

PMID- 8306717
TI  - The efficacy/cost ratio of new therapy. What is the physician's fiduciary
      responsibility?

PMID- 8306718
TI  - How is respiratory medicine growing in Europe?

PMID- 8306719
TI  - Transesophageal echocardiography. Conquering the mediastinum.

PMID- 8306720
TI  - Transesophageal imaging in cor triatriatum.

PMID- 8306721
TI  - Transesophageal echocardiography in endocarditis.

PMID- 8306722
TI  - Home exercise training for cystic fibrosis patients.

PMID- 8306723
TI  - Life expectancy in severe COPD.

PMID- 8306724
TI  - Noninvasive positive pressure ventilation in neuromuscular disease. Enough is
      enough!

PMID- 8306725
TI  - Clubbing of the fingers and smooth-muscle proliferation in fibrotic changes in
      the lung in patients with idiopathic pulmonary fibrosis.
AB  - In our study of 52 patients with idiopathic pulmonary fibrosis (IPF), we found
      that the incidence of clubbing of the fingers was significantly more frequent in
      male than in female patients and in patients who showed lesser grades of
      honeycombing and higher grades of smooth-muscle proliferation in the pulmonary
      fibrotic changes (p < 0.01). Smooth-muscle proliferation in fibrotic changes of
      open lung biopsy specimens correlated with the mode of detection of IPF and the
      presence of clubbing of the fingers, duration of symptoms of the lower
      respiratory tract, and a higher extent of pulmonary infiltrates on chest
      radiographs (p < 0.05). However, the presence of clubbing of the fingers or
      grades of smooth-muscle proliferation in the pulmonary fibrotic changes did not
      correlate with the 2-year survival after open lung biopsy.

PMID- 8306726
TI  - Balloon dilatation and self-expanding metal Wallstent insertion. For management
      of bronchostenosis following lung transplantation. The Toulouse Lung
      Transplantation Group.
AB  - Here we report our experience on the use of balloon dilatation or self-expandable
      metal Wallstent implantation, or both, for the management of twelve bronchial
      stenoses in ten lung transplant recipients during the past two years. Both
      techniques were carried out endoscopically, under fluoroscopic guidance and
      without general anesthesia. Both methods were straightforward, well tolerated,
      and resulted in immediate symptomatic and functional improvement. The first-line
      treatment relied on Wallstent insertion (n = 4) or on balloon dilatation (n = 8).
      Early restenosis occurred in four of eight dilated stenoses and subsequently led
      to Wallstent insertion. Following Wallstent implantation, growth of granulation
      tissue occurred in one case and necessitated repeated balloon dilatations inside
      the stent during the following months. On two occasions, the stenosis was located
      such that the lower end of the Wallstent overlapped the upper lobe bronchus
      orifice. This necessitated laser therapy to eliminate the filaments of the stent
      crossing the lobar orifice, preventing subsequent obstruction. Laser therapy was
      followed, in one case, by a fibroinflammatory stenosis which was successfully
      treated by balloon dilatation inside the prosthesis. At the time of writing, the
      mean +/- SE of the follow-up after Wallstent implantation is 15.3 +/- 2.7 (range:
      6 to 32) months. Most Wallstent prostheses are overgrown with bronchial
      epithelium. We conclude (1) that self-expanding metal Wallstent implantation is a
      safe procedure and good alternative to silicone stent insertion for the treatment
      of bronchostenosis following lung transplantation, provided granulomas are not
      present and (2) that balloon dilatation, although possibly leading to
      recurrences, can be used to allow inflammatory tissue to mature or to dilate
      restenoses inside the Wallstent.

PMID- 8306727
TI  - Respiratory muscle strength and hemodynamics in chronic heart failure.
AB  - To examine whether respiratory muscle weakness is associated with cardiac
      function and/or exercise capacity in chronic heart failure (CHF), 23 patients
      with CHF were evaluated with respiratory muscle strength, pulmonary function
      tests, cardiac catheterization, and exercise test. The subjects were divided into
      three groups on their New York Heart Association (NYHA) functional class. Group A
      consisted of 13 patients with NYHA functional classification class 3 or 4, group
      B consisted of 10 patients with NYHA classification class 2, and group C
      consisted of 15 age-matched normal controls. Respiratory muscle strength was
      assessed with maximal static inspiratory mouth pressure at residual volume level
      and expiratory mouth pressure at total lung capacity level (PImax, PEmax,
      respectively). Pulmonary functions in patients with CHF showed almost normal.
      PImax in group A was significantly less than that in group B or C, although PImax
      in group B was not significantly different from that in group C. In the patients
      with CHF, PImax correlated positively with cardiac index and maximal oxygen
      consumption (r = 0.460 and r = 0.503, p < 0.05, respectively). These findings
      suggest that inspiratory muscle strength, which was impaired in patients with
      severe CHF, may be dependent on cardiac function and may be one of the limiting
      factors on impaired exercise capacity in the patients with CHF.

PMID- 8306728
TI  - Relation of T-wave polarity in precordial V1 lead to right or left circumflex
      coronary pathoanatomy in acute inferior myocardial infarction.
AB  - OBJECTIVE: To test the hypothesis that right ventricular (RV) involvement in
      inferoposterior wall acute myocardial infarction (AMI) may affect precordial T
      wave polarity, relation of T-wave polarity in lead V1 to right (RCA) or left
      circumflex (LCX) coronary pathoanatomy was examined. METHODS: The study
      population included the patients with initial inferoposterior wall AMI due to RCA
      (n = 61) or LCX (n = 19) occlusion within 5 h of symptom onset and 100 normal
      controls. The patients with RCA disease were further divided into four subgroups
      based on the site of coronary occlusion and the direction of the ST shift in lead
      V1: group A1 (n = 27), proximal RCA occlusion with isoelectric or elevated ST
      segment; group A2 (n = 7), proximal occlusion with ST depression; group B1 (n =
      8), distal RCA occlusion with isoelectric or elevated ST segment; group B2 (n =
      19), distal occlusion with ST depression. Presence or absence of an upright T
      wave in lead V1 (> or = 0.15 mV) was evaluated. RESULTS: The patients with
      proximal RCA disease showed a higher incidence of upright T wave (71 percent)
      than the controls (27 percent) (p < 0.001), patients with LCX disease (26
      percent) (p < 0.01), and those with distal RCA disease (19 percent) (p < 0.001).
      Among the four subgroups of RCA disease, the incidence of upright T wave was
      highest in group A1 (90 percent), lowest in group B2 (6 percent), and
      intermediate in controls (27 percent) (p < 0.001) for group A1 vs controls, and p
      < 0.05 for controls vs group B2). CONCLUSIONS: These findings suggest that
      concomitant RV involvement in inferoposterior wall AMI modifies T-wave polarity
      of lead V1, which is ordinarily expected to be reciprocally drawn to negativity
      when infarct is limited to the inferoposterior wall of the left ventricle, to the
      positivity.

PMID- 8306729
TI  - Bronchial hyperresponsiveness to acetylcholine in patients with vasospastic
      angina pectoris.
AB  - STUDY OBJECTIVE: To investigate the similarity between coronary vasospasm and
      bronchial spasm. DESIGN: Nonrandomized, case-control study. SETTING: Referral
      based clinics for cardiac and pulmonary disease at one secondary care center.
      PATIENTS: Seventeen patients with vasospastic angina pectoris (VSAP) and 14
      patients with chest pain syndrome (CPS). INTERVENTIONS: Medications prohibited:
      those with known effects on bronchial responsiveness. MEASUREMENT: Induction of
      coronary vasospasm: ergonovine maleate (10, 20, 40 micrograms) injection into
      coronary arteries during coronary angiography. Bronchial responsiveness to
      acetylcholine (ACh): acetylcholine chloride (0.08 to 20 mg/ml) inhalation and
      calculation of the provocative concentration of ACh (PC20-ACh) that revealed 20
      percent fall in FEV1. RESULTS: The median value for PC20-ACh in patients with
      VSAP, 7.80 mg/ml, was significantly lower than that in patients with CPS, > 20.0
      mg/ml (p < 0.01 by Mann-Whitney U test). The PC20-ACh in patients with VSAP,
      however, was correlated neither with the responsive threshold of ergonovine
      maleate, which induced coronary vasospasm, nor with the duration from the latest
      angina attack. CONCLUSION: These results suggest that bronchial responsiveness
      was increased in most patients with VSAP, but not with CPS. We therefore
      speculate that patients with VSAP may also have hypercontractibility to ACh of
      noncoronary systemic smooth muscles.

PMID- 8306730
TI  - Torsades de pointes induced by erythromycin.
AB  - We describe two patients who develop torsades de pointes in a temporal
      relationship to the intravenous administration of erythromycin lactobionate in
      the absence of other drugs or metabolic abnormalities known to cause the
      arrhythmia. We also review the current literature regarding this topic, including
      other case histories and the evidence for erythromycin's effect on cardiac
      tissue. Due to the increasing use of erythromycin in clinical practice, we
      believe it is important that all physicians be made aware of this potential
      complication, which was not recognized at our institutions until these patients
      were seen by one of us (B.G.).

PMID- 8306731
TI  - Diagnosis of traumatic mediastinal hematoma with transesophageal
      echocardiography.
AB  - In patients with blunt chest trauma, early diagnosis of mediastinal hematoma is
      important, because it could be associated with thoracic vessel injury.
      Mediastinal hematoma is generally evoked because of a widened mediastinum on
      chest radiograph, but radiologic diagnosis may lead to excessive angiography
      being performed. Transesophageal echocardiography (TEE) provides accurate views
      of the mediastinum and can be rapidly performed at the bedside. Thus, we
      conducted a prospective study to define TEE signs of mediastinal hematoma. TEE
      was performed in 22 thoracic trauma patients (trauma group) and in 20 brain-dead
      patients without thoracic trauma (control group). The positive diagnosis of
      mediastinal hematoma was made using thoracic surgery or computed tomographic
      scan. The specificity of TEE was 75 percent and sensitivity was 100 percent. In
      the trauma group, there was only one false positive but angiography discovered a
      traumatic aneurysm of the proximal right subclavian artery. No false negative was
      noted. We described three different TEE signs of mediastinal hematoma: (1) an
      increased distance between the probe and the aortic wall; (2) a double contour of
      the aortic wall; and (3) visualization of the ultrasound signal between the
      aortic wall and the visceral pleura. The distance between the esophageal probe
      and the aortic wall was the most accurate sign because it could be easily
      obtained; the threshold value for this distance was 3 mm. TEE appears to be an
      accurate method to diagnose traumatic mediastinal hematoma.

PMID- 8306732
TI  - Transesophageal echocardiography in diagnosis of infective endocarditis.
AB  - STUDY OBJECTIVE: To determine whether transesophageal echocardiography (TEE) was
      superior to transthoracic echocardiography (TTE) in defining valvular vegetations
      and diagnosing clinical infective endocarditis (IE) in patients suspected of
      having this infection. PATIENTS AND METHODS: Between April 1989 and May 1991, 64
      febrile patients with clinical and/or microbiologic risk factors for IE were
      prospectively enrolled. Patients underwent both TEE and TTE, which were
      interpreted in a blinded fashion as to the patient's clinical status. Clinical
      criteria for the diagnosis of IE were compared with TEE and TTE findings to
      delineate the ability of the two echocardiographic techniques to define valvular
      vegetations and to establish the clinical diagnosis of vegetative IE. RESULTS:
      Thirty-four valves had typical valvular vegetations demonstrated by either TEE or
      TTE. Transesophageal echocardiography was more sensitive than TTE in identifying
      valvular vegetations (33/34 vs 23/34 instances, respectively; p = 0.004). Also,
      TEE was better at identifying smaller vegetations (< 1 cm) than TTE; 12 patients
      with such vegetations were identified by TEE as compared with only 5 of 12
      identified by TTE (p = 0.02). Of the 64 patients enrolled, 30 (47 percent) were
      classified as having "definite" or "probable" IE by modified von Reyn criteria.
      Among these 30 patients, TEE was significantly more sensitive than TTE at
      documenting vegetative valvular lesions (26/30 [87 percent] vs 18/30 [60
      percent], respectively) (p < 0.01). Both TEE and TTE were highly specific (91
      percent) in delineating valvular vegetations in this patient population; two of
      the three false-positive TEE studies for valvular vegetations occurred in
      patients with a history of IE. All nine periannular complications of IE were
      identified by TEE, as compared with only two being defined by TTE (p = 0.001).
      CONCLUSIONS: Transesophageal echocardiography is significantly more sensitive
      than TTE and highly specific in both confirming the clinical diagnosis of IE, as
      well as in identifying valvular vegetations in patients at risk for this
      infection. Our data also support the concept that TEE is the echocardiographic
      method of choice for defining small vegetations and periannular complications in
      IE.

PMID- 8306733
TI  - Mitral valve calcification as an index of left ventricular dysfunction in
      patients with end-stage renal disease on peritoneal dialysis.
AB  - OBJECTIVE: To determine whether mitral valve or anulus calcification (MC) in
      patients with end-stage renal disease is associated with abnormalities of left
      ventricular (LV) structure and function, cardiac characteristics of 55 patients
      undergoing continuous ambulatory peritoneal dialysis (CAPD) with (n = 26; age: 59
      +/- 10 years) vs without (n = 29; age: 58 +/- 12 years) MC were analyzed using
      echocardiography and Doppler echocardiography. Sclerosis of the mitral valve
      anulus was detected in 18 (7 women, 11 men; age: 58 +/- 10 years) patients,
      sclerosis of mitral valve leaflets in 24 (13 women, 9 men; age: 59 +/- 10 years)
      patients. Patients with MC had higher systolic arterial blood pressure before
      initiation of dialysis therapy (191/104 mm Hg vs 173/94 mm Hg; p < 0.05) and
      higher calcium-phosphorus products (55 +/- 13 vs 42 +/- 16; p < 0.05) during CAPD
      therapy than those without MC. Neither prevalence nor severity of MC was related
      to dialysis duration or patient age. Systolic LV function was reduced (ejection
      fraction: 58 +/- 12 percent vs 65 +/- 13 percent; p < 0.05) and LV end-diastolic
      diameters were dilated (54 +/- 5 vs 50 +/- 8 mm; p < 0.05) in patients with MC.
      Left atrial dilatation (73 percent vs 31 percent; p < 0.005) and mitral valve
      regurgitation (65 percent vs 21 percent; p < 0.001) were more frequent in
      patients with vs those without MC. Excluding patients with significant mitral
      regurgitation from pulsed Doppler analysis, diastolic LV function was comparably
      impaired in patients with vs those without MC (maximal early/atrial filling
      velocity ratio: 0.77 +/- 0.25 vs 0.75 +/- 0.22; atrial filling fraction: 47 +/-
      10 percent vs 48 +/- 11 percent; p = NS). The presented data suggest that MC
      follows long-standing and severe arterial hypertension before start of dialysis
      therapy. Therefore, effective blood pressure control in the predialysis period
      may be a tool to prevent these lesions. MC has clinical significance as a marker
      of LV dilatation and reduced LV systolic function in patients with chronic CAPD.

PMID- 8306734
TI  - Incidence of cardiac arrhythmias during intravenous pentamidine therapy in HIV
      infected patients.
AB  - STUDY OBJECTIVE: There have been 15 published cases of probable pentamidine
      induced torsade de pointes (TdP). A prospective analysis of this complication of
      therapy is valuable considering the high frequency of Pneumocystis carinii
      pneumonia in the AIDS population, and the role of pentamidine in its therapy.
      DESIGN: Open, nonrandomized, prospective study of HIV-infected patients receiving
      intravenous pentamidine in a 12-month period. SETTING: Walter Reed Army Medical
      Center, a tertiary care, referral-based facility in Washington, DC. PATIENTS:
      Eighteen HIV-infected patients were enrolled with informed consent; four were
      withdrawn from statistical analysis after receiving only one or two doses of
      empiric intravenously administered pentamidine. MEASUREMENTS AND RESULTS: Daily
      12-lead electrocardiography, echocardiography, weekly signal-averaged
      electrocardiography, and weekly 24-h ambulatory electrocardiography were
      performed on each patient. Of the 14 subjects, 3 developed TdP. These 3 patients
      and 2 others developed a prolonged rate corrected, QT interval (QTc) to greater
      than 0.48 s (max QTc mean, 0.55 s, mean increase, 0.12 s). The QTc prolongation
      was noted in all five patients by the fourth daily dose (4 mg/kg/d) of
      pentamidine. The other 9 patients developed minimal change in QTc intervals
      throughout therapy (max QTc mean, 0.45 s; mean increase, 0.03 s). The maximum QTc
      increase was significantly different between these two cohorts (p < 0.03). The
      occurrence of TdP in the subgroup of patients developing prolonged QTc intervals
      to greater than 0.48 s (3 of 5 patients), or a change in QTc of greater than 0.08
      s (3 of 4 patients) over individual baseline also was significant (p = 0.03 and p
      = 0.01, respectively). No baseline clinical variables associated with TdP or QTc
      prolongation were identified. CONCLUSION: Intravenously administered pentamidine
      frequently results in QTc prolongation with a subsequent risk of TdP in HIV
      infected patients. All patients treated with intravenously administered
      pentamidine should be evaluated with baseline and daily ECGs, at least during the
      first week of therapy, and should be closely monitored for a change in the QT
      interval. An increase in QTc to above 0.48 s or greater than 0.08 s above
      baseline carries a significant risk for proarrhythmia, and in this instance,
      continuous electrocardiographic monitoring or an alternative antibiotic regimen
      should be considered.

PMID- 8306735
TI  - Regional deposition and regional ventilation during inhalation of pentamidine.
AB  - In most patients, the deposition of aerosolized pentamidine (AP) is less in the
      apex of the lung relative to the base. As the apex of the lung is relatively less
      ventilated than the base, it is possible that reduced regional ventilation may
      explain the inhomogeneity in regional drug deposition. The purpose of this study
      was to measure the relationship between regional deposition of AP and regional
      ventilation, and the influence of particle size and airway caliber on this
      relationship. Ten subjects with HIV infection who were receiving prophylaxis with
      AP were recruited. Using krypton (81mKr), we measured regional ventilation during
      treatment with AP, labeled with 99mTc. Two nebulizers were used (Respirgard II
      and Fisoneb) that produced particles of different size. In addition, patients
      were studied with and without a bronchodilator because changes in airway geometry
      can affect sites of particle deposition. There was no significant correlation
      between regional ventilation and regional particle deposition (r = 0.00, linear
      regression). Particle deposition in the upper lobes relative to the lower lobes
      was less than would be predicted by regional ventilation, by a ratio of 0.84 +/-
      0.03 (mean +/- SE). Using two-way analysis of variance (ANOVA), the upper to
      lower zone deposition pattern was not affected by either nebulizer or by the use
      of albuterol. The Fisoneb had significantly more central deposition relative to
      the jet nebulizer (mean +/- SE, skC/P: Fisoneb 1.3 +/- 0.1, Respirgard 1.1 +/-
      0.1, p = 0.005, two-way ANOVA). The use of a bronchodilator did not significantly
      affect the central/peripheral deposition pattern. We conclude that differences in
      deposition between upper and lower lung regions are not accounted for simply by
      differences in regional ventilation in patients undergoing prophylaxis with AP.
      In assessing the cause of regional inhomogeneities of pharmaceutical aerosol
      deposition (and in devising strategies to achieve more uniform distribution),
      regional ventilation should be measured directly rather than be inferred from the
      deposition pattern of the aerosol.

PMID- 8306736
TI  - Rapid clinical diagnosis of pulmonary abnormalities in HIV-seropositive patients
      by auscultatory percussion.
AB  - A prospective, blinded study of pulmonary findings in hospitalized patients with
      HIV infection compared auscultatory percussion (AusP) with conventional
      percussion (ConP) and conventional auscultation (ConA) using chest radiographs as
      the gold standard. Sixty-three patients had chest radiographs and were examined
      by one to three examiners. Seventy of the 126 lungs had radiographic
      abnormalities (55.6 percent). Auscultatory percussion proved to be the most
      sensitive of all techniques for each examiner (range, 51.0 to 69.6 percent) for
      detecting radiographic abnormalities and also had higher likelihood ratios for
      two of the three examiners; AusP also had the highest likelihood ratio pooled
      across examiners. Of the 166 abnormal results of lung examinations, the
      combination of AusP and ConA detected 31 more abnormalities than ConP and ConA
      combined, with 14 of these being diagnosed with Pneumocystis carinii pneumonia.
      No abnormalities were detected by ConP that were not detected by AusP. These
      findings suggest that AusP, a rapid clinical maneuver, is more sensitive and
      specific than ConA and ConP in determining pulmonary abnormalities in HIV
      infected inpatients.

PMID- 8306737
TI  - Cavitary coccidioidomycosis with fungus ball formation. Diagnosis by fiberoptic
      bronchoscopy with coexistence of hyphae and spherules.
AB  - Pulmonary cavitary coccidioidomycosis with fungus ball formation was observed in
      two individuals with hemoptysis. The first patient had no overt compromise; the
      second was an insulin-dependent diabetic. In both, fiberoptic bronchoscopy was
      performed and cultures yielded Coccidioides immitis. The coexistence of spherules
      and hyphae of C immitis was seen histologically on bronchoscopic biopsy specimen
      of one cavitary lesion. Specific antifungal therapy and surgical excision were
      withheld and each patient has done well. This report provides for the first time
      nonsurgical confirmation that C immitis can produce an intracavitary fungus ball.

PMID- 8306738
TI  - Utility of inhaled pentamidine prophylaxis in lung transplant recipients.
AB  - The incidence of Pneumocystis carinii pneumonia (PCP) has been shown to be high
      posttransplantation in the absence of prophylaxis. For this reason, lung
      transplant recipients routinely receive prophylaxis. We report on our results
      using aerosolized pentamidine prophylaxis in nine patients post-lung
      transplantation (eight single lung transplants, one double). The patients
      received monthly treatments of 300 mg of aerosolized pentamidine for a mean of
      10.6 months (range, 4 to 21 months). Patients were routinely monitored with
      serial pulmonary function studies and bronchoscopy as clinically indicated. Two
      of the patients experienced bronchospasm in response to the therapy. None of the
      patients experienced any episodes of PCP during the period of inhaled pentamidine
      prophylaxis. Inhaled pentamidine is a safe and effective form of PCP prophylaxis
      and may be used instead of sulfamethoxazole-trimethoprim in patients who have a
      sulfa allergy or other untoward sulfa side effects.

PMID- 8306739
TI  - The effect of exogenous surfactant therapy on lung function following
      cardiopulmonary bypass.
AB  - OBJECTIVE: Pilot study to investigate the effect of exogenous surfactant therapy
      on lung function following cardiopulmonary bypass (CPB). DESIGN: Prospective
      randomized controlled study. SETTING: Adult intensive care unit of a postgraduate
      cardiothoracic hospital. PATIENTS: Sixteen adult patients undergoing elective
      coronary artery revascularization surgery without a history of preoperative
      respiratory disease. INTERVENTIONS: Artificial lung-expanding compound (ALEC,
      Britannia Pharmaceuticals, Crawley, UK) 3.2 g, was given via a bronchoscope 60
      min after bypass in eight patients. Eight control subjects received air. MAIN
      OUTCOME MEASUREMENTS: Lung function tests during IPPV (arterial blood gas
      tensions, Crs, FRC, TLco, KCO) were measured prior to CPB, before therapy, and at
      regular intervals up to 180 min afterwards. RESULTS: The CPB caused a significant
      impairment of lung function in both groups with an increase in A-a gradient (+47
      +/- 11 mm Hg in the ALEC group and +44 +/- 17 mm Hg in controls) and reductions
      in FRC (-290 +/- 121 ml in the ALEC group and -470 +/- 132 ml in controls), TLco
      (-1.6 +/- 0.3 ml/min/mm Hg in the ALEC group and -2.2 +/- 0.3 ml/min/mm Hg in
      controls), and Crs (-10 +/- 1 ml/cm H2O in the ALEC group and -21 +/- 4 ml/cm H2O
      in controls). The ALEC therapy did not affect A-a gradient, FRC, and Crs compared
      with controls. However, TLco was significantly lower in the ALEC group following
      therapy (120 min after treatment -0.1 +/- 0.3 ml/min/mm Hg in ALEC group and +1.0
      +/- 0.3 ml/min/mm Hg in controls). CONCLUSIONS: A single 3.2-g dose of ALEC
      administered as a bolus bronchoscopically does not improve lung function
      following CPB and may impair gas transfer.

PMID- 8306740
TI  - What is hypopnea, anyway?
AB  - Quantitation of apneas and hypopneas is routinely included in studies of
      epidemiology, diagnosis, and treatment of sleep-disordered breathing (SDB). The
      definition of apnea appears clear-cut in the sleep literature. In contrast, the
      literature contains remarkable variety in both recording techniques and
      definitions of hypopnea. The purpose of this study was to characterize the
      variety in the definitions and techniques used to identify hypopnea in clinical
      sleep laboratories. One hundred surveys were mailed to 100 accredited sleep
      laboratories. Each laboratory was asked to provide its criteria and equipment
      used to define hypopnea. Forty-five surveys (45 percent) were returned. No two
      laboratories used the same definition and measures of hypopnea. We conclude that
      there is no consensus about either recording techniques or definitions of
      hypopnea. Thus, epidemiologic studies and reports of interventions on SDB that do
      not include precise definitions of hypopnea must be interpreted with caution.

PMID- 8306741
TI  - Predictive factors of long-term compliance with nasal continuous positive airway
      pressure treatment in sleep apnea syndrome.
AB  - The long-term acceptability of treatment with nasal continuous positive airway
      pressure (CPAP) was studied prospectively in 44 patients with obstructive sleep
      apnea syndrome. At 14 months on the average after starting treatment with CPAP,
      30 patients (68 percent) were found to be compliant (characterized by use of the
      apparatus every night throughout the night, for more than 5 h per night). The
      daily use of nasal CPAP was significantly correlated to the initial
      apnea/hypopnea index (p = 0.013; r = 0.37), as well as to the percentage of light
      sleep (p = 0.045; r = 0.30) and slow-wave sleep (p = 0.037; r = -0.31) during the
      initial polygraphic recording. We found a strong correlation between the daily
      use of nasal CPAP and the difference in the apnea/hypopnea index (p = 0.025; r = 
      0.34), the difference in mean oxygen saturation during sleep (p = 0.013; r =
      0.38), and the difference in hypersomnia scores (p = 0.006; r = -0.40) obtained
      before and after treatment by nasal CPAP. Thus, patients used CPAP much more if
      they had an initial significant clinical handicap and if they were aware of the
      beneficial effects of CPAP. Under these conditions, patients tended to use the
      apparatus for the optimal length of time, regardless of the side effects linked
      to the treatment. This ensured efficacy and the maintenance of good compliance.
      This study confirms the importance of supervision of the time counter, as well as
      regular encouragement of patients to use the treatment as long as possible each
      night, in order to extract a maximum benefit from treatment by nasal CPAP.

PMID- 8306742
TI  - Effects of short-term NIPPV in the treatment of patients with severe obstructive
      sleep apnea and hypercapnia.
AB  - Although nasal continuous positive airway pressure (CPAP) is effective in the
      treatment of most patients with obstructive sleep apnea (OSA), there is a small
      group of such patients in whom rapid eye movement (REM) hypoventilation and CO2
      retention persist despite the use of CPAP and supplemental oxygen. In this report
      we describe our experience with nocturnal nasal ventilation (nocturnal nasal
      positive pressure ventilation [NIPPV] in such patients and its effectiveness in
      reversing daytime hypercapnia. Thirteen patients, aged 28 to 69 years, with
      severe OSA confirmed on polysomnography, failed to respond to initial CPAP
      therapy. All were grossly obese (body mass index [BMI] > 35 kg.ml-1) and
      hypercapnic (mean PaCO2, 62 mm Hg). Nocturnal nasal ventilation was commenced
      using a volume-cycled ventilator, which was well tolerated in all patients. After
      7 to 18 days of NIPPV, significant improvements in daytime arterial blood gas
      values were achieved, with a rise in arterial oxygen tension from 50 +/- 2.6
      (SEM) to 66 +/- 3 mm Hg (p < 0.001) and a fall in CO2 from 62 +/- 2.5 to 46 +/- 1
      mm Hg (p < 0.0001). Nine of the 13 patients were able to be established on a
      regimen of nasal CPAP after this period, while 3 patients required a longer
      period (up to 3 months) before adequate nocturnal ventilation could be
      maintained. In one patient, the improvements in ventilatory drive achieved with
      NIPPV could not be maintained on CPAP, and she was transferred on to NIPPV long
      term. These results indicate that effective nasal ventilation leads to an overall
      improvement in spontaneous ventilation and blood gas values both awake and
      asleep. We believe this improvement is the result of improved central ventilatory
      drive. Short-term NIPPV provides lasting benefits allowing the majority of such
      patients to resume CPAP therapy. Short-term intervention with this therapy should
      be considered as an interim measure in patients with severe hypercapnic OSA who
      fail to respond to initial CPAP therapy.

PMID- 8306743
TI  - Noninvasive nasal mask ventilation for acute respiratory failure. Institution of
      a new therapeutic technology for routine use.
AB  - OBJECTIVE: We successfully implemented the delivery of noninvasive mechanical
      ventilation for patients with acute respiratory failure, a previously
      controversial use of this technique, using a simplified ventilator (BiPAP) with
      nasal mask. Pilot work showed this mode of support to be effective when
      administered by the members of a research team, and in the current study we were
      able to transfer this responsibility to usual care providers. SETTING: Almost 90
      percent of the patients in this study were in either the 16-bed medical or 31-bed
      surgical intensive care units at our hospital. SUBJECTS: One hundred ten
      hemodynamically stable patients with acute respiratory failure being considered
      for intubation and mechanical ventilation participated in this study. Eighty
      percent were surgical patients, most of whom had hypercapnic failure.
      INTERVENTION: Patients were administered noninvasive ventilatory support using a
      ventilatory support system (BiPAP) applied with a nasal mask. This intervention
      was administered by a research team in the initial 31 patients (special care,
      phase 1). The administration was transferred to usual care personnel in the next
      45 patients (transition, phase 2). Usual care personnel almost exclusively
      administered care in the final 34 patients (usual care, phase 3). RESULTS:
      Withdrawal of ventilatory support for greater than 48 h (successful outcome) was
      about the same during usual care (phase 3, 80 percent) as it was during special
      care (phase 1, 76 percent).

PMID- 8306744
TI  - Long-term nasal intermittent positive pressure ventilation in advanced Duchenne's
      muscular dystrophy.
AB  - The aim of our study was to evaluate the long-term effect of nasal ventilation in
      patients with advanced Duchenne's muscular dystrophy (DMD). To this end, we
      compared the clinical and pulmonary function course of five subjects affected
      with chronic ventilatory failure due to DMD and treated with nasal intermittent
      positive pressure ventilation (NIPPV) with that of an unventilated comparison
      group; the latter consisted of another five patients with DMD, with a similar
      degree of clinical and respiratory functional impairment, who refused long-term
      mechanical ventilation. The duration of the follow-up was 24 months. At the
      conclusion of the trial, all patients treated with NIPPV were still alive; in
      contrast, four of five patients who underwent simple conservative treatment had
      already died (mean survival, 9.7 +/- 5.8 months). After 6 months of follow-up,
      mean loss of FVC and maximal voluntary ventilation was considerably higher in
      nonventilated subjects (respectively: -0.23 L vs +0.03 L and -5 L/min vs -1.5
      L/min). These are the first comparative results confirming that long-term NIPPV
      helps to stabilize pulmonary function and to prolong the expectancy of life of
      patients with DMD.

PMID- 8306745
TI  - Dextromethorphan test for evaluation of congenital predisposition to lung cancer.
AB  - We report the results of an investigation conducted in 992 healthy control
      subjects (854 adults and 138 adolescents) and in 116 subjects with lung cancer
      (LC) for the purpose of detecting those individuals with a possible genetic
      predisposition to lung cancer. The test consists of the oral administration of 64
      mumol of dextromethorphan (DMP) with collection of urine samples over the
      following 8-h period and urine assay of the drug (DMP) and its main metabolite,
      dextrorphan (DOP). The ratio of the urinary concentrations of DMP to those of DOP
      is called the metabolic ratio (DMP/DOP) and is inversely proportional to the DMP
      demethylation rate. The pattern of the metabolic ratio (Log10 DMP/DOP) allowed,
      using a maximum likelihood approach, the identification of three subpopulations
      in the 854 control subjects (adults): (1) probable homozygous extensive
      metabolizers with Log10 DMP/DOP < -1.74 (73.1 percent); (2) probable heterozygous
      intermediate metabolizers with Log10 DMP/DOP in the -1.74 to -0.40 range (22.3
      percent); and (3) probable homozygous poor metabolizers with Log10 DMP/DOP > -0.4
      (4.6 percent). Most of the patients with LC (89 percent) were probable homozygous
      extensive metabolizers. As the latter have a cancer risk that is 2.54-fold
      greater than that of intermediate metabolizers (95 percent confidence interval
      [CI]: 1.37 to 4.73) and 7.43-fold greater than that of poor metabolizers (95
      percent CI: 1.01 to 54.5), their identification by means of the DMP test may be
      particularly useful for subjects exposed to environmental and occupational
      carcinogens. The phenotype test used is similar to that of the debrisoquin test,
      but presents the advantage that DMP is a widely used, harmless drug with a faster
      and simpler urinary assay procedure.

PMID- 8306746
TI  - Fiberoptic bronchoscopy in the evaluation of carcinoma metastatic to the lung.
AB  - To determine the clinical presentation of patients with malignancies metastatic
      to the lung, the diagnostic utility of fiberoptic bronchoscopy (FB), and the
      primary site of malignancies metastasizing endobronchially, we retrospectively
      reviewed 1,853 FB records (1987 to 1991) and selected 111 cases for review. Cases
      were divided on the basis of FB findings into abnormal (44 patients) and normal
      (67 patients). Pulmonary symptoms (cough, hemoptysis, and chest pain) prompted
      referral significantly more often in the abnormal FB group (34/44) than in the
      normal FB group (24/67). The finding of atelectasis on chest radiograph occurred
      more frequently in patients with endobronchial abnormalities. The spectrum of
      extrapulmonary malignancies that metastasize endobronchially has changed during
      the AIDS epidemic. Our study shows the most frequent causes of endobronchial mass
      lesions were Kaposi's sarcoma and the lymphoma group (Hodgkin's disease,
      nonHodgkin's lymphoma, chronic lymphocytic leukemia) and the most common
      malignancies causing submucosal metastases were breast and the lymphoma group. In
      summary, the highest yield from FB can be expected in patients experiencing
      symptoms of cough or hemoptysis and/or having radiographic evidence of
      atelectasis. We propose a new mnemonic "KLAS" (Kaposi's sarcoma, Lymphoma,
      Adenocarcinoma, Sarcoma) to describe the malignancies most likely to metastasize
      endobronchially in the 1990s.

PMID- 8306747
TI  - Detection of lymphomatous involvement of the lung by bronchoalveolar lavage.
      Application of immunophenotypic and gene rearrangement analysis.
AB  - We report three cases of pulmonary involvement of non-Hodgkin's lymphoma in which
      immunophenotypic or gene rearrangement analysis of bronchoalveolar lavage (BAL)
      cells demonstrated monoclonality of T- or B-cell lineage. The first patient had T
      cell lymphoma and developed pulmonary lesions. Surface marker analysis of the BAL
      cells revealed that CD8-positive lymphoid cells were dominant and Southern blot
      analysis of T-cell receptor gene detected gene rearrangement demonstrating
      monoclonality of T-cell lineage. The second patient presented with diffuse
      micronodular shadows on chest radiograph. Marked B-lymphocytosis in BAL fluid
      prompted us to analyze their clonality. The third was a case in which recurrence
      of primary pulmonary lymphoma was suspected. In the second and third case, the
      finding of marked increase in the number of CD 19-positive B lymphocytes with a
      single class of light chains proved a monoclonal population in BAL cells. With
      the review of other cases in our study and the relevant literature, we conclude
      that the clonal analysis of BAL cells is helpful in establishing the diagnosis of
      pulmonary involvement of T- or B-cell lymphoma.

PMID- 8306748
TI  - Effect of a home exercise training program in patients with cystic fibrosis.
AB  - Physical training in patients with pulmonary diseases, including cystic fibrosis
      (CF), may improve exercise tolerance in these patients. Most training programs
      are performed in a clinical setting. Little information is available concerning
      the effect of home exercise training programs in CF patients. The purpose of this
      study was to investigate the effect of a home exercise training program in CF
      patients. Ten adolescent patients (seven male and three female) with CF, mean
      (SD) age 20.6 (6.5) years, participated in a home exercise training program for 3
      months. Pretraining condition was assessed during a control period of 2 months in
      which patients were asked to continue their normal daily activities. Home
      exercise training consisted of cycle training of 15 min at a submaximal workload
      once a day and was supervised by a physiotherapist two times a week. A follow-up
      period of 1 month, in which the patients were advised to continue cycling at home
      without supervision, was included after the training program. Pulmonary function,
      bicycle exercise test performance, and the degree of limitation in activities of
      daily living (ADL) were measured. No significant differences were found between
      the two pretraining assessments. After the training period we found significant
      improvement in maximal exercise capacity (Wmax) (mean [SEM]: 126 [10] W before
      and 146 [11] W after; p = 0.004), maximal oxygen uptake (VO2max) (mean [SEM]:
      31.4 [2.1] ml.kg-1.min-1 before and 36.5 [2.5] ml.kg-1.min-1 after; p = 0.008),
      oxygen pulse (VO2/HR) (mean [SEM]: 10.9 [0.66] ml before and 11.9 [0.74] ml
      after; p = 0.047), and degree of limitation in ADL (mean [SEM]: 2.4 [0.43] before
      and 1.5 [0.48] after; p = 0.019) as compared with the initial values. Since no
      significant differences were found between the posttraining values and the
      results at the end of the follow-up period, the patients were apparently able to
      maintain the training effects during the follow-up period. We conclude that in CF
      patients, a home exercise training program, after clinical assessment of exercise
      tolerance, is an effective and relatively simple treatment to improve physical
      performance and decrease limitation in ADL and should be included in the
      maintenance treatment in these patients.

PMID- 8306749
TI  - Prognosis of severely hypoxemic patients receiving long-term oxygen therapy.
AB  - Two hundred seventy severely hypoxemic (PaO2 < or = 55 mm Hg: mean +/- SD = 48 +/
      6) COPD patients (232 men) were selected for long-term oxygen therapy (LTOT).
      They were old (mean = 66 +/- 8 years), with severe airflow limitation (FEV1 = 30
      +/- 12 percent of predicted), some CO2 retention (PaCO2 = 47 +/- 9 mm Hg), and
      compensated respiratory acidosis. Eighteen percent of the patients presented some
      complicating pleuropulmonary diseases (pleural thickening, sequelae of
      tuberculosis, etc). Overall survival proportion was poor: 70, 50, and 43 percent
      at 1, 2, and 3 years, respectively. The Cox model showed that the factors which
      independently reduced survival were lower CO transfer coefficient, smaller
      intrathoracic gas volume, more severe bronchial obstruction, the fact that oxygen
      administration did not increase PaO2 above 65 mm Hg, increasing age, and the
      presence of chest wall abnormalities. When the patients were divided into three
      groups according to mortality risk, the mean clinical and functional profile of
      the high-mortality risk group was consistent with the prevalence of emphysematous
      lesions. Moreover, the best survivors fitted better into the "bronchitic" type;
      they showed a higher mean PaCO2, suggesting that some degree of hypoventilation
      could delay muscular fatigue and improve survival. The difference in the
      proportion of "emphysematous" and "bronchitic" patients is a possible explanation
      for the variability of the mortality rate reported in literature.

PMID- 8306750
TI  - Inspiratory muscle training in patients with Duchenne muscular dystrophy.
AB  - PURPOSE: The aim of this study was to assess the usefulness of a specific
      inspiratory muscle training in Duchenne muscular dystrophy (DMD). PATIENTS AND
      METHODS: Fifteen patients with DMD started 6 months of training the inspiratory
      muscles and 15 patients served as a control group. Pulmonary and inspiratory
      muscle function parameters were assessed 3 months before and at the beginning of
      training, in the first and third month of training, at the end, and 6 months
      after its cessation. Maximal sniff assessed esophageal and transdiaphragmatic
      pressure values served as indices for global inspiratory muscle strength and
      diaphragmatic strength, respectively. Inspiratory muscle endurance was assessed
      by the length of time a certain inspiratory task could be maintained. RESULTS: In
      10 of the 15 patients, respiratory muscle function parameters improved
      significantly after 1 month of training. Further improvements were to be seen
      after 3 and after 6 months. Even 6 months after the end of training, those
      effects remained to a large extent. In the other five patients, there was no such
      improvement after 1 month of training, which was therefore discontinued. All
      these five patients had vital capacity values of less than 25 percent predicted
      and/or PaCO2 values of more than 45 mm Hg. The 15 control patients had no
      significant change in their respiratory muscle function parameters. CONCLUSION:
      We conclude that a specific inspiratory muscle training is useful in the early
      stage of DMD.

PMID- 8306751
TI  - Inhaled ICI 204,219 blocks antigen-induced bronchoconstriction in subjects with
      bronchial asthma.
AB  - Three inhalation formulations of ICI 204,219 were compared for antagonism of
      antigen-induced bronchoconstriction in 16 subjects with asthma who demonstrated
      reproducible hypersensitivity to allergen during screening challenges. Each
      subject received a single 0.2-mg dose of each formulation and was challenged with
      ragweed 30 min after administration of ICI 204,219 until the forced expiratory
      volume in 1 s (FEV1) decreased by 20 percent or the maximum allergen
      concentration (100 micrograms/ml) was reached. The majority of subjects tolerated
      100 micrograms/ml of allergen without a 20 percent decrease in FEV1. Inhalation
      formulations of ICI 204,219 successfully inhibited bronchoconstriction in
      subjects with reproducible sensitivity to ragweed challenges.

PMID- 8306752
TI  - Interrelationships between pulmonary and extrapulmonary involvement in systemic
      sclerosis. A longitudinal analysis.
AB  - PURPOSE: (1) To evaluate the relationship between the degree of pulmonary
      involvement by systemic sclerosis (SSc) and the degree of involvement of other
      organ systems by SSc at baseline. (2) To assess the degree of impairment in lung
      function at presentation and the annual rate of change in lung function to
      predict the rate of progression of involvement of extrapulmonary organ systems by
      SSc over time. (3) To determine whether survival in patients with SSc can be
      predicted from the degree of lung function impairment at baseline or from the
      annual rate of change in lung function. METHODS: Semiquantitative indices of
      pulmonary and extrapulmonary involvement and pulmonary function tests (PFTs) were
      analyzed and compared in 62 nonsmoking scleroderma patients enrolled in a 3-year
      prospective drug trial, vs 47 in a "study group" who underwent serial evaluation.
      The other 16 "early withdrawals" withdrew prior to the second evaluation. The
      indices of organ system involvement were based on clinical, physiologic, and
      biochemical findings as previously published. The PFTs included total lung
      capacity (TLC), forced vital capacity (FVC), FEV1, and single-breath diffusing
      capacity for carbon monoxide (Dsb). Annualized rates of change in PFTs and
      indices of extrapulmonary involvement were calculated for each subject from data
      collected on at least 2 separate occasions at least 6 months apart. Spearman rank
      correlations were performed between individual baseline PFTs (expressed as
      percent predicted) and (a) indices of extrapulmonary involvement at baseline, (b)
      annualized rates of change in PFTs, and (c) annualized rates of change in indices
      of extrapulmonary involvement. Correlations also were performed between the rate
      of change in each lung function measure and rates of change in indices of
      extrapulmonary involvement. The ability of PFTs at baseline and their rates of
      change to predict cumulative survival was assessed by Cox stepwise regression.
      RESULTS: The degree of impairment in baseline PFTs was related to involvement of
      the right side of the heart but not to other extrapulmonary system involvement.
      Baseline PFTs were not related to the rate of subsequent decline of lung function
      or worsening of extrapulmonary organ system involvement. Subsequent annual rates
      of decline in lung function were related to worsening skin and upper
      gastrointestinal involvement. Cumulative survival may be related to the rate of
      decline in DCO, TLC, and FVC, but was not predicted by impairment in any measure
      of lung function. CONCLUSION: With the exception of involvement of the right side
      of the heart consistent with cor pulmonale, the degree of pulmonary involvement
      by SSc was not correlated with the extent of extrapulmonary involvement. The
      degree of pulmonary involvement by SSc did not predict subsequent worsening of
      either pulmonary or extrapulmonary involvement. Worsening pulmonary involvement
      by SSc, in general, does not correlate with worsening involvement of
      extrapulmonary organ systems, except for the skin and upper gastrointestinal
      tract. A rapid decline in DCO or lung volumes may predict poor survival.

PMID- 8306753
TI  - Oligo-2',5'-adenylate synthetase in pulmonary sarcoidosis and idiopathic
      pulmonary fibrosis.
AB  - Oligo-2',5'-adenylate synthetase (2,5AS) is an enzyme induced by all types of
      interferon (IFN). We measured the levels of 2,5AS activity in peripheral blood
      mononuclear leukocytes (PBML) and bronchoalveolar lavage fluid (BALF) cells of
      patients with pulmonary sarcoidosis (SAR), idiopathic pulmonary fibrosis (IPF),
      and normal controls (NC). In NC, the levels of BALF cell 2,5AS activity were
      approximately seven times as high as the levels of PBML 2,5AS activity. The
      measurement 2,5AS activity from isolated cells showed that the levels of 2,5AS
      activity are independent of cell differential from PBML and BALF cells. The
      levels of PBML and BALF cell 2,5AS activity in SAR were both significantly high
      in comparison with those in NC. In patients with IPF, the levels of PBML 2,5AS
      activity were significantly increased as compared with those in NC, whereas there
      was no significant difference regarding the levels of BALF cell 2,5AS activity
      between patients with IPF and NC. These results suggest the following: (1) in
      patients with SAR, IFN production is enhanced both in the alveolar space and
      peripheral circulation; (2) in patients with IPF, IFN production is greatly
      enhanced in the circulation, whereas IFN production is not enhanced in the
      alveolar space; and (3) IFN may contribute to the pathogenesis of SAR and IPF.

PMID- 8306754
TI  - Normal values for single exhalation diffusing capacity and pulmonary capillary
      blood flow in sitting, supine positions, and during mild exercise.
AB  - Previous approaches to the measurements of pulmonary diffusing capacity (DL) and
      pulmonary capillary blood flow (QC) utilized either the rebreathing or the single
      inhalation technique in conjunction with radioisotope gas and mass spectrometry.
      In the present study, we utilized a newly developed rapid infrared analyzer in
      conjunction with the slow single exhalation technique on 100 healthy volunteers
      to establish normal values for DL and QC under sitting, supine, and exercise
      conditions. The exercise level was determined by a target heart rate: HRex =
      ([HRmax - HRrest]/3) + HRrest. Prediction equations based on regressions on age,
      sex, height, or weight were then computed for sitting, supine, and exercise
      values. We found that mean DL and QC increased by approximately 12 percent and 8
      percent, respectively, from sitting to supine posture, and by approximately 30
      percent and 100 percent, respectively, from sitting (rest) to mild exercise.
      These results provided a database for further studies in the single exhalation
      method in various clinical settings.

PMID- 8306755
TI  - Radiographic course of pulmonary manifestations in Wegener's granulomatosis under
      immunosuppressive therapy.
AB  - Eleven patients with generalized Wegener's granulomatosis were studied. Pulmonary
      involvement occurred 1 month earlier than a rapid rise of serum creatinine value.
      Under immunosuppressive therapy, nodules and infiltrations abated slower in
      patients with bronchopulmonary superinfection (mean, 30 days) compared with
      patients without superinfection (mean, 18 days). In the short run, radiographic
      course was a better indicator for therapeutic success than the course of
      cytoplasmatic antineutrophil cytoplasm antibody titer. If the pulmonary findings
      did not begin to clear within 1 week after treatment had been started, either
      superinfection or insufficient immunosuppression was present. In this situation,
      a more aggressive therapy in combination with antibiotics is suggested.

PMID- 8306756
TI  - Erythromycin does not directly affect neutrophil functions.
AB  - To determine whether erythromycin could affect neutrophil functions, we measured
      N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced chemotaxis and superoxide
      generation of neutrophils in the presence of erythromycin at various
      concentrations. Erythromycin had no effect on either of them. We further
      confirmed that intracellular free calcium concentration ([Ca2+]i) was not
      influenced by FMLP stimulation in the presence of erythromycin. Our results
      indicate that erythromycin has no direct effects on neutrophil functions in
      vitro, although it is reported that erythromycin inhibits the local migration of
      neutrophils in the small airways of subjects with asthma.

PMID- 8306757
TI  - Two studies of the clinical effectiveness of the nicotine patch with different
      counseling treatments.
AB  - OBJECTIVE: To assess the effectiveness of transdermal nicotine therapy for
      smoking cessation and suppression of withdrawal severity in conjunction with two
      different adjuvant counseling treatments. DESIGN: Two independent randomized
      placebo-controlled double-blind trials. SETTING: Smoking cessation clinic.
      SUBJECTS: Eighty-eight (study 1) and 112 (study 2) adult volunteers motivated to
      quit smoking. INTERVENTIONS: Eight weeks of 22-mg transdermal nicotine therapy
      with group counseling (study 1); 4 weeks of 22 mg followed by 2 weeks of 11-mg
      transdermal nicotine therapy with brief individual counseling (study 2). MAIN
      OUTCOME MEASURES: Modified point prevalence (7 consecutive days of nonsmoking) at
      the end of patch treatment and 6 months after treatment initiation was assessed
      by self-report and biochemically confirmed; survival analyses were also conducted
      for both studies to compare treatment efficacy. Also, we examined the impact of
      the nicotine patch on specific withdrawal symptoms (anger, anxiety, awakening,
      difficulty concentrating, depression, hunger, impatience, and craving). RESULTS:
      Transdermal nicotine treatment produced higher cessation rates at the end of
      treatment than did placebo with both adjuvant counseling interventions: 59
      percent vs 40 percent (p < 0.05 in study 1) and 37 percent vs 20 percent (p <
      0.05 in study 2), respectively. Smoking cessation efficacy was maintained 6
      months after initiation of treatment: 34 percent vs 21 percent (p = 0.08 in study
      1) and 18 percent vs 7 percent (p = 0.05 in study 2). Survival analyses also
      revealed significant group differences in efficacy in both studies. Nicotine
      patches also suppressed a variety of withdrawal symptoms, including craving in
      the first weeks after patients quit smoking. CONCLUSION: Transdermal nicotine
      effectively augments smoking cessation rates with two different types of
      counseling treatment. Overall, the nicotine patch approximately doubles the
      sustained rate of smoking cessation. Additionally, the nicotine patch provides
      relief from some tobacco withdrawal symptoms.

PMID- 8306758
TI  - Weaning from prolonged mechanical ventilation. The experience at a regional
      weaning center.
AB  - STUDY OBJECTIVE: The aim of this study was to describe the facility, patient
      population, outcome of treatment, and survival of patients transferred to a
      regional weaning center (RWC) after prolonged mechanical ventilation in the ICU
      setting. DESIGN: Retrospective record review. SETTING: Regional weaning center.
      PATIENTS: Four hundred twenty-one consecutive ventilator dependent patients were
      transferred from ICU care for attempted weaning over a 36-month period.
      MEASUREMENT AND RESULTS: Acute catastrophic surgical, traumatic, or septic
      illness resulted in ventilator dependency with much greater frequency than
      decompensated COPD. Of the 421 patients, 116 died and 287 survived with outcome
      known at discharge. Of the 287 who survived, 212 were freed from ventilator
      support. Patients who weaned were ventilator-dependent for 46.9 +/- 2.9 days
      before transfer to the RWC. Almost half of those weaned were discharged to their
      homes. Survival at 6 months and 1 year after discharge was 44 percent and 28
      percent respectively, and it was greater for those at home than for those
      discharged to an extended care facility (ECF). The RWC care was approximately
      $1,500 per patient day less costly than ICU care, and $208 per patient day less
      costly than noninvasive respiratory care unit care. CONCLUSIONS: Selected
      patients who become ventilator dependent for prolonged periods in the ICU may be
      transferred to an RWC with the expectation of successful weaning in a majority of
      cases.

PMID- 8306759
TI  - Rapid shallow breathing (frequency-tidal volume ratio) did not predict extubation
      outcome.
AB  - This was a prospective study of 52 patients that were extubated in our medical
      intensive care unit. Rapid shallow breathing, represented by a ratio of frequency
      to tidal volume (f/VT) of more than 105, was evaluated either on continuous
      positive airway pressure or pressure support prior to extubation as a marker of
      extubation outcome. Twelve out of 13 patients (92 percent) with rapid shallow
      breathing (f/VT ratio > 105) were successfully extubated. Out of 9 extubation
      failures only 1 patient had a f/VT ratio more than 105 (11 percent). A measured
      f/VT ratio of less than 105 had a sensitivity and specificity of 72 and 11
      percent, respectively, for extubation success. Patients who had unsuccessful
      outcomes were ventilated for a significantly more prolonged period (9.6 +/- 6.8 d
      vs 4.6 +/- 3.9 d, unpaired t test, p = 0.004). We conclude that the presence of
      rapid shallow breathing during a weaning trial with the patient on partial
      ventilatory support does not necessarily preclude successful extubation.

PMID- 8306760
TI  - A predictive equation for determination of resting energy expenditure in
      mechanically ventilated patients.
AB  - STUDY OBJECTIVE: To evaluate an equation that estimates resting energy
      expenditure from two easily obtained measurements--expired carbon dioxide and
      minute ventilation, and compare the results of this equation with standard
      methods of estimating and measuring caloric expenditure in mechanically
      ventilated patients. DESIGN: Prospective evaluation in a consecutive, unselected
      cohort. SETTING: Medical, surgical, and coronary intensive care units in a
      university hospital. PATIENTS: Twenty-five patients (16 to 79 years of age)
      receiving mechanical ventilation. INTERVENTION: Indirect calorimetry (IC), minute
      ventilation (VE), and partial pressure of expired carbon dioxide (PECO2) were
      obtained on all patients. Harris-Benedict equations were calculated and corrected
      for known stress factors (HBc). Calculated energy expenditure (CEE) was
      determined using the following equation: CEE = 9.27 x VE x PECO2 CEE was then
      compared with IC and HBc. MEASUREMENTS AND RESULTS: The IC was interpretable in
      22 of 25 patients, and CEE was significantly better at estimating caloric
      requirements than HBc. The mean absolute difference between CEE and IC was
      significantly less than between HBc and IC (118 +/- 96 vs 302 +/- 269, p < .003).
      CEE estimated caloric requirements to within 200 kcal of IC in 16 of 22 (72
      percent); HBc estimated within 200 kcal of IC in 9 of 22 (41 percent).
      CONCLUSIONS: Minute ventilation and expired carbon dioxide measurements are
      easily and inexpensively obtainable. Energy expenditures calculated from these
      measurements (CEE) compare favorably with values obtained from a metabolic cart
      and are significantly more accurate than HBc.

PMID- 8306761
TI  - Endotracheal tube and tracheobronchial obstruction as causes of hypoventilation
      with high inspiratory pressures.
AB  - Two cases of difficult ventilation are presented, the first caused by
      endotracheal tube obstruction with nasal turbinate, and the second caused by
      tracheobronchial obstruction with blood clots. The clinical presentation in each
      case was characterized by extreme difficulty in ventilating and severe
      hypercapnia despite vigorous ventilatory efforts with either a mechanical
      ventilator or resuscitator bag. A simple manipulation of the endotracheal tube
      cuff helped to differentiate between increased impedance caused by endotracheal
      tube obstruction as opposed to increased respiratory system impedance beyond the
      tip of tube. In the second patient, in whom even a short interruption of
      ventilation was poorly tolerated, simultaneous rigid bronchoscopy (for removal of
      intratracheal masses) and ventilation via endotracheal tube were successfully
      performed.

PMID- 8306762
TI  - Predictors of total parenteral nutrition-induced lipogenesis.
AB  - OBJECTIVE: To evaluate the incidence and cause of parenteral nutrition-induced
      lipogenesis. DESIGN: Retrospective patient review. SETTING: A 40-bed
      predominantly surgical ICU. PATIENTS: One hundred forty patients receiving
      central venous nutrition and mechanical ventilatory support. INTERVENTIONS:
      Indirect calorimetry was used to determine patient's measured energy expenditure
      (MEE) and respiratory quotient (RQ). Additionally total caloric intake (TCAL),
      glucose infusion rate, basal energy expenditure (BEE), estimated stress factor,
      and calculated energy expenditure (CEE) were assessed in each patient.
      MEASUREMENTS AND MAIN RESULTS: Net fat synthesis was found as RQs exceeded 1 in
      47 percent of patients. Statistically significant differences in oxygen
      consumption, CO2 production, measured energy expenditure, total and carbohydrate
      caloric intake, and glucose infusion rate were found between groups of patients
      with an RQ < or = or > 1. Seventy-three percent of patients with glucose infusion
      rates > 4 mg/kg-min had RQs > 1. CONCLUSIONS: Net fat synthesis was found in a
      surprisingly large number of critically ill patients receiving central venous
      nutrition. Many of these patients received carbohydrate calories in excess of
      their measured energy expenditure, even though it appeared that they needed this
      level of caloric intake by clinical assessment. The high carbohydrate total
      parenteral nutrition (TPN) solutions with lipids provided only for prevention of
      essential fatty acid depletion resulted in an unacceptably high incidence of fat
      synthesis. The results suggest that caloric intake may be optimized in critically
      ill patients using indirect calorimetry. When calorimetry is not available, a
      total caloric intake of up to 140 percent of the BEE with glucose infusion rates
      not exceeding 4 mg/kg-min and fats providing 40 to 60 percent of calories will
      meet the energy requirements of most critically ill patients without forcing the
      RQ > 1.

PMID- 8306763
TI  - The benefit of lateral radiographs in an intensive care unit.
AB  - The portable anteroposterior (AP) radiograph (CXR) is an essential component of
      clinical management in the intensive care unit (ICU). In view of the immobility
      of patients, and overlying tubes, wires, and catheters, lateral (LAT) CXRs are
      infrequently ordered. We constructed a portable acrylic (Plexiglas) CXR cassette
      holder and were able to obtain reproducible quality LAT CXRs in the ICU. Of the
      72 simultaneously obtained AP and LAT CXRs, 60 were technically acceptable for
      interpretation. We found an 11 percent incidence of either unexpected conditions
      or we were able to improve on the AP CXR interpretation. Lateral CXRs should be
      obtained routinely in the ICU in select patients.

PMID- 8306764
TI  - Pulmonary aspiration in mechanically ventilated patients with tracheostomies.
AB  - The purpose of this descriptive study was to evaluate feeding aspirations in
      adult patients receiving long-term mechanical ventilatory support, including the
      incidence of aspirations, the frequency of silent (clinically inapparent)
      aspirations, and differences between aspirators and nonaspirators. Aspiration
      data were determined by review of videofluoroscopic (VF) tapes of modified barium
      swallow procedures performed on 83 medically stable patients admitted to a
      chronic ventilator unit. Demographic and clinical variables were obtained from
      review of subjects' medical records. Forty-two subjects (50 percent) aspirated
      during VF testing and 37 of 48 (77 percent) aspirations were silent. Subjects who
      aspirated were significantly older than those who did not aspirate (p = 0.007).
      Swallowing disorders were common, particularly disturbances of the pharyngeal
      phase. We conclude that feeding aspiration is seen frequently in patients with
      tracheostomies receiving prolonged positive pressure mechanical ventilation.
      Advanced age increases the risk of aspiration in this population. Episodes of
      aspiration are not consistently accompanied by clinical symptoms of distress to
      alert the bedside observer to their occurrence.

PMID- 8306765
TI  - Pulmonary gangrene. A complication of bacterial pneumonia.

PMID- 8306766
TI  - Strategies for reestablishing coronary blood flow during the acute phase of
      myocardial infarction.

PMID- 8306767
TI  - Measurement of right ventricular volume in human explanted hearts using ultrafast
      cine computed tomography.
AB  - The quantitative measurement of right ventricular (RV) volume has been attempted
      by a number of methods, including nuclear magnetic resonance imaging, contrast
      angiography, echocardiography, and radionuclide angiography. All of these methods
      have limitations. Ultrafast cine computed tomographic (CT) scan is a new
      technology that may have an important role in on-line ventricular volume
      measurements. Twelve human explanted hearts, fixed in formalin, were subjected to
      ultrafast cine CT scans to estimate RV volume. The volumes derived from the CT
      scans were compared with actual fluid volumes needed to fill the RV volume
      measurements. All measurements were conducted independently by two observers.
      Actual RV volumes in the 12 hearts ranged from 29.8 ml to 174.6 ml. A strongly
      significant correlation between actual volume and CT volume was seen (r = 0.99).
      Agreement between observers was also seen to be highly significant (r = 0.992).
      Limitations to accurate in vivo assessment due to bolus injection of contrast
      medium might include alterations in ventricular pressure change. Similarly,
      differentiation of the endocardial border with contrast may not be as sharp as
      that with an air-tissue interface. This study demonstrates that RV volumes can be
      reliably determined by ultrafast cine CT scans in explanted hearts. On-line
      systolic and diastolic volumes and thus stroke volume, ejection fraction, etc,
      can be accurately defined independent of cardiac orientation. This technique
      offers opportunities to study ventricular function under various conditions.

PMID- 8306768
TI  - Breathlessness with bumps, lumps, and humps.

PMID- 8306769
TI  - Cough, fever, and cavitating pulmonary lesions in a 21-year-old construction
      worker.

PMID- 8306770
TI  - Comparison of four methods for calculating diffusing capacity by the single
      breath method.
AB  - In 283 patients referred for testing in an outpatient pulmonary function
      laboratory, we studied the single-breath diffusing capacity of the lungs for
      carbon monoxide (Dco) using the Ogilvie (Og), Jones-Meade (JM), Epidemiological
      Standardization Project (ESP), and three-phase iterative methods (3PIT, similar
      to the three equation method). The Dco maneuvers were performed using automated
      equipment and American Thoracic Society (ATS) recommended procedures. There were
      small but significant differences in mean Dco, the ESP method yielding the
      largest, followed in order by JM, 3PIT, and Og methods. The 3PIT and JM Dcos were
      in close agreement in all degrees and patterns of pulmonary function abnormality.
      The Og Dco method was 6 percent less than JM in patients with normal pulmonary
      function, although the difference was less in patients with expiratory flow
      limitation, restriction, or reduced Dco. There were no differences in the
      reproducibility of Dco measurements among the methods. Based on these results and
      a review of the literature, we conclude the following: (1) when measuring single
      breath Dco using automated equipment that follows ATS recommended procedures for
      collecting a single expired gas sample of 500-ml volume, calculated Dco is
      largest using ESP method, following by JM, 3PIT, and Og methods; (2) in patients
      with reduced Dco associated with obstructive or restrictive abnormalities, the
      Og, 3PIT, and JM timing methods are nearly equivalent; and (3) reproducibility of
      Dco is the same by all methods.

PMID- 8306771
TI  - Biplane transesophageal echocardiographic diagnosis of cor triatriatum.
AB  - A transthoracic echocardiogram disclosed a linear structure in the left atrium of
      an adult presenting with atypical chest pain. Biplane transesophageal
      echocardiography revealed a cor triatriatum. The longitudinal plane was most
      useful for the assessment of the membrane orifice and the Doppler flow pattern.

PMID- 8306772
TI  - Phenytoin toxicity associated with hypoalbuminemia in critically ill patients.
AB  - Four critically ill patients developed phenytoin toxicity. Hypoalbuminemia or
      concomitant displacing drugs resulted in an increased fraction of unbound drug.
      Clinical findings included gradual decrease in level of consciousness and
      cerebellar signs. Marked phenytoin toxicity can occur in critically ill patients
      with hypoalbuminemia and can often be detected only by direct measurement of free
      phenytoin levels.

PMID- 8306773
TI  - Sinus arrest associated with dipyridamole infusion.
AB  - We describe a case of prolonged sinus arrest resolved by external cardiac massage
      following intravenous infusion of dipyridamole, during a thallium myocardial
      perfusion test. The arrhythmia, presumably due to an acute drug adverse effect,
      had not been previously described (to our knowledge) as a complication of
      dipyridamole stress testing.

PMID- 8306774
TI  - Noncardiogenic pulmonary edema complicating massive verapamil overdose.
AB  - Noncardiogenic pulmonary edema has not been (to our knowledge) previously
      reported associated with a verapamil overdose. We describe a 27-year-old woman
      who developed this complication after an overdose of 15, 120-mg verapamil tablets
      (total of 1,800 mg). This report illustrates the possibility of serious pulmonary
      embarrassment in the course of a verapamil overdose and the need to avoid
      excessive crystalloid administration during the hypotensive period.

PMID- 8306775
TI  - Tracheal malacoplakia.
AB  - Malacoplakia is a rare granulomatous disease well described in the urinary tract
      but which rarely involves the lung. We report for the first time, to our
      knowledge, tracheal localization of this unusual disorder. The larynx and
      probably kidneys were also involved. Differential diagnosis, physiopathology, and
      treatments are discussed.

PMID- 8306776
TI  - Dynamic right ventricular outflow obstruction after single-lung transplantation.
      Biplane transesophageal echocardiographic findings.

PMID- 8306777
TI  - Superior vena cava syndrome caused by a right apical tense bulla.
AB  - Superior vena cava (SVC) syndrome is caused by several diseases, although to our
      knowledge, a bullous lesion has not been reported previously. In the present
      case, severe pleural adhesion prevented the expanding bulla from stretching the
      visceral pleura and from compressing the residual lung, subsequently causing
      compression of the SVC and thus SVC syndrome.

PMID- 8306778
TI  - Mercury inhalation poisoning and acute lung injury in a child. Use of high
      frequency oscillatory ventilation.
AB  - Acute mercury inhalation poisoning is a rare cause of acute lung injury. It is
      commonly fatal in the young child because of progressive pulmonary failure. We
      describe a 3-month-old infant who survived this insult with the use of high
      frequency oscillatory ventilation. This form of support may be an option in the
      patient with severe adult respiratory distress syndrome (ARDS) or air leak
      syndromes.

PMID- 8306779
TI  - Staphylococcus aureus pericarditis in HIV-infected patients.
AB  - Serious infections caused by Staphylococcus aureus in HIV-infected patients have
      been reported. Contributing factors in the development of invasive S aureus
      infections include a high rate of skin and nasal colonization, frequent
      dermatologic disease, and the use of intravenous catheters. The authors report
      three cases of S aureus pericarditis in HIV-infected patients. While cases of
      viral, mycobacterial, and malignant pericardial effusions in HIV-infected
      patients have been reported, a review of the literature disclosed only three
      cases of bacterial pericarditis. Despite appropriate antibiotic therapy and
      drainage, a patient's condition may abruptly deteriorate and progress to
      tamponade. Early recognition of bacteremia and pericarditis and monitoring for
      cardiac tamponade, along with aggressive treatment, can result in a favorable
      outcome, but mortality remains high, particularly when S aureus is the causative
      agent.

PMID- 8306780
TI  - Lymphocytic alveolitis in a crematorium worker.
AB  - An asymptomatic cremator was found incidentally to have lymphocytic alveolitis by
      bronchoalveolar lavage, and the basis for this finding was investigated. No known
      causes of lymphocyte alveolitis including sarcoidosis, hypersensitivity
      pneumonitis, berylliosis, tuberculosis, or fungal diseases of the lung were
      found. By exclusion, therefore, exposure to formaldehyde and/or to compounds in
      the residual ash likely were etiologic in the development of the lymphocytic
      alveolitis.

PMID- 8306781
TI  - Ventricular fibrillation in a patient with exercise-induced anaphylaxis, normal
      coronary arteries, and a positive ergonovine test.
AB  - Exercise-induced anaphylaxis (EIA) is a rare form of physical allergy. Although
      histamine release is a feature of EIA, and histamine provocation of coronary
      spasm has been described, serious cardiac arrhythmias in EIA have not been
      reported. Exercise-induced anaphylaxis was diagnosed in a survivor of out-of
      hospital cardiac arrest due to ventricular fibrillation after ECG signs of
      coronary spasm. Coronary artery disease was excluded. Ergonovine provocation
      induced coronary spasm in this patient. This is, to the authors' knowledge, the
      first description of ventricular fibrillation in EIA, possibly due to coronary
      spasm.

PMID- 8306782
TI  - Pleural effusion in multiple myeloma.
AB  - We report the first case of IgA-kappa multiple myeloma presenting as a
      myelomatous and eosinophilic pleural effusion with increased adenosine deaminase
      activity. In a review of the literature, 80 percent of myelomatous pleural
      effusions are due to IgA multiple myeloma.

PMID- 8306783
TI  - Myasthenia gravis associated with small-cell carcinoma of the lung.
AB  - A 49-year-old man complained of a 3-month history of progressive generalized
      muscle weakness. He was diagnosed as having small-cell lung carcinoma at the same
      time. He received an intravenous injection of edrophonium chloride with
      remarkable improvement of muscle strength. Electromyographic studies revealed a
      compound muscle action potential that decreased after repetitive stimulation.
      These findings were considered representative of myasthenia gravis (MG), and
      inconsistent with Eaton-Lambert syndrome. The appearance of MG with small-cell
      lung carcinoma seems to be very rare, but possible.

PMID- 8306784
TI  - Bilateral pneumothorax after percutaneous transthoracic needle biopsy. Evidence
      for incomplete pleural fusion.
AB  - Although the pleural cavities are anatomically separate in humans, we describe
      bilateral pneumothoraces that occurred after percutaneous needle biopsy of the
      lung. In some individuals, there may be communication between the pleural spaces;
      it is important for those performing interventional procedures to be aware of
      this uncommon anatomic variant.

PMID- 8306785
TI  - Syphilitic pneumonitis in an HIV-infected patient.
AB  - Pneumonitis and symptomatic hepatitis are very rare complications of syphilis.
      Symptomatic hepatitis and subclinical reticulonodular pulmonary infiltrates were
      observed when an HIV-infected patient presented with secondary syphilis. The
      Jarisch-Herxheimer reaction included a flare of hepatitis symptoms, resembling
      cholangitis. In a patient with syphilis, it may be appropriate to delay an
      aggressive evaluation for suspected pneumonitis or cholangitis pending the
      outcome of specific antitreponemal therapy.

PMID- 8306786
TI  - Simultaneous occurrence of three primary lung cancers.
AB  - We present a patient with three lung cancers composed of adenosquamous carcinoma,
      adenocarcinoma, and squamous cell carcinoma. Marked response was obtained in
      squamous cell carcinoma components following chemotherapy, but not in
      adenocarcinoma components. Even multiple malignant lesions of the lung might have
      a chance to be controlled by a combination of chemotherapy and surgery.

PMID- 8306787
TI  - Diagnosis of coronary artery atheroembolism by right ventricular endomyocardial
      biopsy.
AB  - A case of coronary artery atheroembolism in a 54-year-old man, presenting as
      worsening congestive heart failure 2 months after mitral valve repair, left
      ventricular aneurysmectomy, and coronary artery bypass grafting, is reported. The
      diagnosis was made by right ventricular endomyocardial biopsy. The authors
      believe this to be the first such account in the literature.

PMID- 8306788
TI  - Chlorambucil-associated pneumonitis.
AB  - A patient developed an interstitial pneumonitis while receiving chlorambucil for
      a chronic lymphocytic leukemia (cumulative dose, 8,340 mg). Withdrawal of drug
      treatment was followed by rapid improvement in the clinical condition.
      Bronchoalveolar lavage showed a T-lymphocytic alveolitis, whereas blood
      lymphocytes were predominantly of the B phenotype. The T-lymphocytic alveolitis
      persisted 6 weeks after drug therapy cessation with a predominant CD8+ phenotype,
      as observed in some hypersensitivity pneumonitis induced by drugs.

PMID- 8306789
TI  - Platypnea related to constrictive pericarditis.
AB  - Platypnea is the rare symptom of dyspnea in the upright position, which is
      relieved by assumption of the recumbent position. This symptom has been
      previously described in association with several conditions, but never with
      constrictive pericarditis. The authors report the case of a patient with
      constrictive pericarditis and severe platypnea, which resolved after
      pericardiectomy.

PMID- 8306790
TI  - Cardiac tamponade secondary to giant lymph node hyperplasia (Castleman's disease)
AB  - A unique association of giant lymph node hyperplasia (Castleman's disease) and
      cardiac tamponade is presented. Although pleural effusions have been previously
      described with Castleman's disease, the authors believe this to be the first
      report of pericardial effusion and tamponade with this entity. The development of
      effusions may be due to an inflammatory syndrome sometimes seen with the plasma
      cell variant of this disease.

PMID- 8306791
TI  - Pulmonary edema associated with radiocontrast material.

PMID- 8306792
TI  - Abnormal lymphatics and sarcoidosis.

PMID- 8306793
TI  - Floating around. Use of the pulmonary artery (Swan-Ganz) catheter in critical
      care.

PMID- 8306794
TI  - Interventional radiology concerns.

PMID- 8306795
TI  - Laceration of the cuff of an endotracheal tube during percutaneous dilatational
      tracheostomy.

PMID- 8306796
TI  - Bronchial responsiveness to methacholine in insulin-dependent diabetic patients
      with autonomic neuropathy.

PMID- 8306797
TI  - Actinobacillus actinomycetemcomitans pneumonia with possible septic embolization.

PMID- 8306798
TI  - Effects of inverse-ratio ventilation on cardiorespiratory measurements in severe
      respiratory failure.

PMID- 8306799
TI  - Is chest CT performed too often?

PMID- 8306800
TI  - Increased adenosine deaminase activity in Q fever pneumonia with pleural
      effusion.

PMID- 8306801
TI  - Familial primary pulmonary hypertension.

PMID- 8306802
TI  - The medical treatment of primary pulmonary hypertension. Proven and promising
      strategies.

PMID- 8306803
TI  - Histopathology of primary pulmonary hypertension.

PMID- 8306804
TI  - Primary pulmonary hypertension. The American experience.

PMID- 8306805
TI  - Primary pulmonary hypertension. Case series from the United Kingdom.

PMID- 8306806
TI  - Primary pulmonary hypertension. Case series from France.

PMID- 8306808
TI  - Pathophysiology of pulmonary hypertension. A role for endothelial dysfunction.

PMID- 8306807
TI  - The International Primary Pulmonary Hypertension Study (IPPHS).

PMID- 8306809
TI  - Simulation of human plasma levels of beta-lactams in mice by multiple dosing and
      the relationship between the therapeutic efficacy and pharmacodynamic parameters.
AB  - A mathematical multiple dosing model was designed so that human plasma
      concentration-versus-time curves of beta-lactams are reproduced in mouse plasma.
      The pharmacokinetic parameters of FK037, a new injective cephalosporin, in
      volunteers and in the mice model were 6,966 and 6,894 ml, respectively, for Vc,
      2.592 and 2.698/h for alpha, 0.2875 and 0.3027/h for beta, and 0.9079 and 1.0506
      for K21. Therefore, real pharmacokinetics of humans were reproduced in mice by
      this method. The 8-hour therapeutic efficacy (the decrease of the viable counts
      in the lung) against pneumonia with Staphylococcus aureus and Pseudomonas
      aeruginosa in mice was well correlated with the time above MIC value, but not
      with AUC, Cmax or AUC above MIC. These results indicate that this model was
      valuable to evaluate the beta-lactam antibiotics for predicting their clinical
      efficacy and that the time above MIC is an important factor in selecting beta
      lactam agents and determining dosage in pulmonary infection.

PMID- 8306810
TI  - Increased resistance of encapsulated Bacteroides fragilis to clindamycin.
AB  - The antimicrobial susceptibility and in vitro growth curve of 4 nonencapsulated
      and 4 encapsulated isolates of Bacteroides fragilis were determined for
      clindamycin. The MIC of the nonencapsulated isolates was 1-2 dilutions less
      (0.062-0.25 microgram/ml) than the MIC for their encapsulated counterparts (0.25
      0.5 microgram/ml). No difference was noted in the bacterial growth of the
      nonencapsulated or encapsulated isolates when incubated without clindamycin. The
      decline in the number of nonencapsulated isolates was significantly lower (p <
      0.05) as compared to the encapsulated isolates when incubated with 0.1 or 0.4
      microgram/ml of clindamycin. These results illustrate the higher susceptibility
      of nonencapsulated B. fragilis isolates to clindamycin as compared to their
      encapsulated counterparts. Since B. fragilis becomes more encapsulated during the
      infectious process, this finding underscores the advantage of early antimicrobial
      prophylaxis and therapy.

PMID- 8306811
TI  - Activity of twenty-one antimicrobial agents including l-ofloxacin against
      quinolone-sensitive and -resistant, and methicillin-sensitive and -resistant
      Staphylococcus aureus.
AB  - There is a need to identify alternative agents to vancomycin for the treatment of
      infections with methicillin-resistant Staphylococcus aureus (MRSA). One candidate
      is the l isomer of ofloxacin (DR-3355). We tested 520 frozen MRSA isolates, 248
      fresh MRSA isolates, and 375 fresh methicillin-susceptible S. aureus (MSSA)
      isolates from Minnesota, and 600 clinical isolates of S. aureus (150 MRSA and 450
      MSSA) from Illinois. Over 90% of the MRSA strains were resistant to 32
      micrograms/ml of oxacillin. Of the 520 frozen MRSA, 24% were susceptible to < or
      = 2 micrograms/ml ofloxacin, and an additional 74% were susceptible to ofloxacin
      between 8 and 16 micrograms/ml. More than 98% of all strains were susceptible to
      < or = 16 micrograms/ml ofloxacin or l-ofloxacin. All the quinolones had a
      bimodal distribution of in vitro activity, but for only ofloxacin and l-ofloxacin
      was activity confined to a very narrow range.

PMID- 8306812
TI  - Susceptibility of methicillin-resistant Staphylococcus aureus to minocycline and
      other antimicrobials.
AB  - The incidence of methicillin-resistant Staphylococcus aureus (MRSA) is on the
      rise, especially in nosocomial and intravenous-drug-abuse-related infections,
      with a concomitant increase in morbidity, mortality and health care costs. At
      present the drug of choice, vancomycin, which must be administered intravenously,
      is expensive and can cause serious side effects in vancomycin-intolerant
      patients. Recently, minocycline has received much attention as an antibiotic to
      combat the increasing frequency of MRSA-related infections. We tested 102 recent
      clinical isolates of MRSA from tertiary-care patients and found none to be
      resistant to minocycline, with minimum inhibitory concentrations of < 1-2
      micrograms/ml. The only other drug that inhibited all the strains was vancomycin,
      followed by ciprofloxacin (87%), clindamycin (55%) and chloramphenicol (52%).
      Gentamicin, beta-lactams, tetracycline and trimethoprim-sulfamethoxazole had
      little or no activity against our isolates of MRSA.

PMID- 8306813
TI  - Postantibiotic effect, and postantibiotic effect of subinhibitory concentrations,
      of sparfloxacin on gram-negative bacteria.
AB  - The postantibiotic effect (PAE), the postantibiotic sub-MIC effect (PA SME), and
      the sub-MIC effect (SME) of a new oral quinolone, sparfloxacin, were determined
      for different strains of gram-negative bacteria. A PAE was induced by 10 x MIC of
      sparfloxacin for 2 h and the antibiotic was then eliminated by washing and
      dilution. The PA SME was studied by adding different sub-MICs during the
      postantibiotic phase, and the SME by exposing the controls to the sub-MICs alone.
      Growth curves were followed for 20 h by continuous monitoring of optical density
      in an automatic incubator. Sparfloxacin induced a PAE of 0.9-2.4 h for all
      strains except two clinical strains of Enterobacter cloacae. In accordance with
      earlier experiments with sparfloxacin and gram-positive bacteria, this study
      showed a PA SME that was nearly equal to the PAE plus the effect of the
      subinhibitory concentration alone (SME).

PMID- 8306814
TI  - The in vitro effects of ceftibuten on the host defense mechanism.
AB  - The in vitro effects of ceftibuten on human polymorphonuclear leukocyte (PMN)
      chemotaxis, phagocytosis and chemiluminescence were investigated. PMN from
      healthy adult donors were incubated for 1 h in medium alone or in medium
      containing increasing concentrations of ceftibuten (4, 8 and 40 times the MIC for
      Escherichia coli). Up to 40 MIC ceftibuten did not significantly interfere with
      the function of PMN.

PMID- 8306815
TI  - Influenza virus-inhibitory effects of intraperitoneally and aerosol-administered
      SP-303, a plant flavonoid.
AB  - The phenolic biopolymer SP-303 was evaluated against experimentally induced
      influenza A (H1N1) virus infections in mice in a series of experiments. When 30,
      10 or 3 mg/kg/day of SP-303 were administered intraperitoneally once daily for 8
      days beginning either 48 h before or 4 h after virus exposure, only lung
      consolidation was significantly reduced; extended (p < 0.01) mean day to death
      was also seen in the late-therapy groups. The high dosage was lethally toxic in
      this experiment. A small-particle aerosol (SPA) of 10, 5 and 2.5 mg/ml of SP-303,
      administered for 1 h three times daily for 5 days beginning 4 h after virus
      exposure, exerted a similar antiviral effect. Twice-daily 1-hour SPA treatments
      for 3 days beginning 24 h before virus exposure using 4.3 mg/ml of SP-303
      resulted in significant increases in mean day to death and reductions of lung
      consolidation but no inhibition of lung virus titer. Declines in influenza
      induced arterial oxygen saturation, as determined by pulse oximetry, were less in
      all animals treated with SP-303 by SPA, but this reduced decline was significant
      (p < 0.01) only in the last experiment. Mice receiving SP-303 by SPA exhibited
      consistent but reversible hypothermia immediately after termination of treatment.

PMID- 8306816
TI  - Intrapericardial mitomycin C for the management of malignant pericardial effusion
      secondary to gastric cancer: case report and review.
AB  - In a 57-year-old man with recurrent gastric cancer, cardiac tamponade due to
      malignant pericardial effusion developed. Echocardiographically guided
      pericardiocentesis followed by an intrapericardial instillation of mitomycin C
      provided a complete control of the pericardial effusion, and no adverse effects
      were observed with this procedure. An intrapericardial instillation with
      effective anticancer agents is therefore considered to be useful for the
      management of malignant pericardial effusion.

PMID- 8306817
TI  - Antibiotic therapy for typhoid fever.
AB  - A retrospective clinical study was conducted to evaluate the efficacies of
      various kinds of antibiotics on 804 patients with typhoid fever. Of 16 regimens
      studied, ofloxacin and enoxacin achieved 100 cure rates without relapse or
      carriage of Salmonella typhi within 3 months. Their good safety profiles and
      relatively lower costs were very cost-effective for treatment of typhoid fever,
      and they can be recommended as the first-line choices for routine management of
      this disease. In addition, our results suggested that ceftriaxone treatment of
      typhoid fever should be given at higher dose: not less than 3 g once daily, or
      over a longer period, to reduce the incidence of relapse.

PMID- 8306818
TI  - Single-dose antibiotic prophylaxis in maxillofacial surgery.
AB  - The clinical efficacy of short-term antimicrobial prophylaxis with either one
      shot of ceftriaxone (1 g) or a course of 3 injections of a fixed combination of
      mezlocillin (2 g) and oxacillin (1 g) administered over 24 h was studied in a
      prospective randomized clinical study of 100 patients undergoing elective
      maxillofacial surgery. Tissue and plasma concentrations of the antibiotics were
      determined by high-pressure liquid chromatography in 6 tumor surgery patients
      from each treatment group. Statistical analysis showed the treatment group to be
      comparable both demographically and with respect to the types of surgery
      performed and the durations of the procedures. Only 1 patient in each group
      developed a postoperative wound infection. It is concluded that 1 g ceftriaxone
      given 30 min preoperatively meets the pharmacokinetic requirements for
      perioperative antimicrobial prophylaxis in maxillofacial surgery.

PMID- 8306819
TI  - Aureobasidium mansoni meningitis in a leukemia patient successfully treated with
      amphotericin B.
AB  - Aureobasidium mansoni fungal meningitis in a 30-year-old leukemic patient is
      reported. This is the first reported case of Aureobasidium spp. central nervous
      system infection. The patient was successfully treated with systemic antifungal
      chemotherapy with a total dose of 2.2 g of amphotericin B.

PMID- 8306820
TI  - Lipid peroxides in the polychemotherapy of cancer patients.
AB  - There is evidence that a variety of anticancer drugs exert their cytotoxic
      activity by a free-radical-mediated mechanism. These drugs include anthracyclines
      such as adriamycin, daunorubicin, 4-epi-adriblastin as well as bleomycin,
      procarbazine, vincristin, cyclophosphamide, etoposide and mitomycin C. The aim of
      this study was to investigate whether cancer patients who underwent
      polychemotherapy (n = 44) show more signs of oxidative stress in plasma than a
      group of healthy controls (n = 52). As an index of free radical generation,
      plasma concentrations of thiobarbituric-acid-reactive substances (TBARS), well
      accepted as markers for oxidative stress, were determined by fluorometric
      detection after separation by high-performance liquid chromatography. In 12
      cases, the TBARS were measured both before and after a chemotherapy course. After
      chemotherapy, 10 of 12 patients showed a marked increase in plasma TBARS
      concentration compared to values measured before therapy [9.02 +/- 1.84 nmol/ml
      (n = 12) vs. 11.58 +/- 2.49 nmol/ml (n = 12); p = 0.002, t-test for paired
      observations]. Tumor patients in general had significantly larger amounts of
      TBARS in plasma in comparison with a control group [mean 11.88 +/- 3.51 nmol/ml
      (n = 44) vs. 7.51 +/- 2.14 nmol/ml (n = 52); p < 0.001, t test]. Our results are
      evidence that repetitive polychemotherapy with radical-generating compounds may
      exceed the antioxidative capacities of cancer patients and may lead to oxidative
      stress.

PMID- 8306822
TI  - A 'zebra' chromosome arising from multiple translocations involving non
      homologous chromosomes.
AB  - An alloplasmic wheat line carrying a 'zebra' chromosome z5A was isolated from the
      derivatives of an Elymus trachycaulus x Triticum aestivum cv Chinese Spring
      hybrid. Chromosome z5A was named zebra because of its striped genomic in situ
      hybridization pattern. z5A consists of four chromosome segments derived from E.
      trachycaulus and four chromosome segments, including the centromere, from wheat.
      The short arm of z5A paired with the telocentric chromosome 1H(t)S of E.
      trachycaulus and the long arm with the long arm of normal 5A. z5A also carried
      several genetic markers derived from 1H(t)S. Chromosome 1H(t) was the only E.
      trachycaulus chromosome found in the sib plants of a previous generation from
      which z5A was derived. Monosomic 5A and telocentric chromosome 5AL were also
      found in most of the sib plants. The zebra chromosome most probably originated
      from spontaneous multiple translocations between chromosomes 5A and 1H(t)S or 5A
      and 1H(t).

PMID- 8306821
TI  - The RNA polymerase I-specific transcription initiation factor UBF is associated
      with transcriptionally active and inactive ribosomal genes.
AB  - We have characterized an anti-NOR (nucleolar organizer region) serum (P419) from
      a patient with rheumatoid arthritis and show that it contains antibodies directed
      against the RNA polymerase I-specific transcription initiation factor UBF. This
      serum reacts with UBF from a variety of vertebrate cells as revealed both by
      immunoblotting and by indirect immunofluorescence. We have used the P419 serum to
      study the intracellular localization of this transcription factor at the light
      and electron microscopic level. In interphase cells, UBF exhibits a pronounced
      punctate pattern and is found to be associated with necklace-like structures,
      which appear to reflect the transcriptionally active state of the nucleolus.
      Inhibition of rRNA synthetic activity caused either by nutritional starvation or
      by actinomycin D treatment resulted in a marked decrease in the number and in a
      significant increase in the size of UBF-positive granules. Under all experimental
      conditions applied, UBF was exclusively found within the nucleolus and was not
      released into the nucleoplasm or cytoplasm. During mitosis, UBF was found to be
      concentrated at the chromosomal NOR indicating that a significant quantity, if
      not all, of this factor remains bound to the ribosomal transcription units. From
      this we conclude that UBF is associated both with transcriptionally active and
      inactive rRNA genes and, therefore, changes in the intracellular localization of
      UBF are very likely not involved in rDNA transcription regulation.

PMID- 8306823
TI  - Organization of the Y chromosome in testis cells of fetal, subadult and adult
      mice as determined by in situ hybridization.
AB  - In order to reveal the time-course of decondensation of the Y chromosome in
      Sertoli cells, testes preparations of fetal, subadult and adult laboratory mice
      in different developmental stages were hybridized in situ with biotinylated probe
      pY353/B, which binds along the entire long arm of the mouse Y chromosome. All
      fetal and subadult testicular cells exhibited tightly compacted hybridization
      signals, indicating highly condensed Y chromosomes. Diffuse signals, indicating
      decondensation of the Y chromosome were found for the first time in the
      structurally differentiated Sertoli cells of 35 to 40 day old animals. Since this
      coincides with the appearance of mature sperm nuclei, a correlation between
      decondensation of the Y chromosome and its activity in sperm maturation and/or
      sperm motility can be presumed.

PMID- 8306824
TI  - Atomic force microscopy of mammalian sperm chromatin.
AB  - We have used the atomic force microscope (AFM) to image the surfaces of intact
      bull, mouse and rat sperm chromatin and partially decondensed mouse sperm
      chromatin attached to coverglass. High resolution AFM imaging was performed in
      air and saline using uncoated, unfixed and unstained chromatin. Images of the
      surfaces of intact chromatin from all three species and of an AFM-dissected bull
      sperm nucleus have revealed that the DNA is organized into large nodular
      subunits, which vary in diameter between 50 and 100 nm. Other images of partially
      decondensed mouse sperm chromatin show that the nodules are arranged along thick
      fibers that loop out away from the nucleus upon decondensation. These fibers
      appear to stretch or unravel, generating narrow smooth fibers with thicknesses
      equivalent to a single DNA-protamine complex. High resolution AFM images of the
      nodular subunits suggest that they are discrete, ellipsoid-shaped DNA packaging
      units possibly only one level of packaging above the protamine-DNA complex.

PMID- 8306825
TI  - A meiotic DNA polymerase from Coprinus cinereus: further purification and
      characterization.
AB  - A meiotic DNA polymerase that is present at a high level of activity in meiotic
      cells of a basidiomycete, Coprinus cinereus, was purified to near homogeneity
      using synthetic RNA homopolymer [poly(C)] cellulose column chromatography. This
      report presents the first extensive purification and characterization of any
      eukaryotic DNA polymerase having a role in meiosis. This enzyme is a single
      polypeptide with a molecular mass of 65,000. Activity in this enzyme requires
      magnesium ions and occurs at an optimal pH of 7.5. It is strongly inhibited by
      dideoxythymidine triphosphate but is relatively insensitive to aphidicolin and N
      ethylmaleimide and can use poly(C)/oligo(dG)12-18 as a template-primer.
      Polymerase activity can be found only in cells at meiotic prophase, even though
      the enzyme has been identified in somatic cells in an inactive state using
      immunoblot analysis. Its distinctive distribution makes possible a genetic and
      biochemical analysis of functional role of a meiotic DNA polymerase in meiotic
      recombination, repair and synthesis.

PMID- 8306826
TI  - Phosphorylation of linker histones by cAMP-dependent protein kinase in mitotic
      micronuclei of Tetrahymena.
AB  - Linker histones (LHs) in transcriptionally inactive, mitotically dividing
      micronuclei of Tetrahymena thermophila, alpha, beta, gamma and delta, are highly
      phosphorylated in vivo. Analysis of the derived sequences of these LHs suggests
      that none of these polypeptides contain sites of phosphorylation by p34cdc2, the
      kinase thought to play an essential role governing the entry of all cells into
      mitosis. Surprisingly alpha, beta, gamma and delta each contain sites for
      phosphorylation by cyclic AMP-dependent kinase (PKA). p34cdc2 kinase
      phosphorylases H1 in vitro but fails to phosphorylate alpha, beta, gamma and
      delta. Conversely, PKA phosphorylates each of the micronuclear LHs but is unable
      to phosphorylate macronuclear H1. Micronuclear LHs labeled in vivo with
      [32P]phosphate were purified by reverse phase HPLC. Phosphoamino acid analysis
      showed that all four micronuclear LHs are phosphorylated exclusively on serine
      residues in vitro. Cyanogen bromide mapping of alpha, beta, gamma and delta
      labeled in vivo or in vitro by PKA indicates that each LH is phosphorylated only
      on peptides that contain either optimum (RR/KXS) or less optimum (RXXS) PKA
      sequences. This study suggests that PKA or a PKA-like activity(ies), but not
      p34cdc2 kinase, is(are) responsible for the in vivo phosphorylation of LHs in the
      mitotic micronucleus of Tetrahymena. We suggest that, at least in Tetrahymena,
      PKA-driven phosphorylation or dephosphorylation plays a significant role in the
      control of mitotic processes such as chromosome condensation.

PMID- 8306828
TI  - Chromatin structures of Kluyveromyces lactis centromeres in K. lactis and
      Saccharomyces cerevisiae.
AB  - We have investigated the chromatin structure of Kluyveromyces lactis centromeres
      in isolated nuclei of K. lactis and Saccharomyces cerevisiae by using micrococcal
      nuclease and DNAse I digestion. The protected region found in K. lactis is
      approximately 270 bp long and encompasses the centromeric DNA elements, KlCDEI,
      KlCDEII, and KlCDEIII, but not KlCDE0. Halving KlCDEII to 82 bp impaired
      centromere function and led to a smaller protected structure (210 bp). Likewise,
      deletion of 5 bp from KlCDEI plus adjacent flanking sequences resulted in a
      smaller protected region and a decrease in centromere function. The chromatin
      structures of KlCEN2 and KlCEN4 present on plasmids were found to be similar to
      the structures of the corresponding centromeres in their chromosomal context. A
      different protection pattern of KlCEN2 was detected in S. cerevisiae, suggesting
      that KlCEN2 is not properly recognized by at least one of the centromere binding
      proteins of S. cerevisiae. The difference is mainly found at the KlCDEIII side of
      the structure. This suggests that one of the components of the ScCBF3-complex is
      not able to bind to KlCDEIII, which could explain the species specificity of K.
      lactis and S. cerevisiae centromeres.

PMID- 8306829
TI  - Follow-up after screening for colorectal neoplasms with fecal occult blood
      testing in a controlled trial.
AB  - PURPOSE: The aim of this study was to investigate the number of new colorectal
      neoplasms during the first seven years after the end of rescreening in a
      prospective randomized screening study. METHODS: 27,700 inhabitants of Goteborg
      born between 1918 and 1922 (60-64 years old) who were randomly allocated to a
      control or a test group in 1982 were followed up. All people in the latter group
      were offered six fecal occult blood tests and rescreening 16 to 22 months later.
      RESULTS: One hundred one carcinomas were diagnosed in the screened group and 128
      in the control group during the seven years of follow-up. The number of
      carcinomas in the test group was half that in the control group during the first
      two years of follow-up, but equal during the rest of the follow-up period. The
      distribution of carcinomas according to Dukes classification was significantly
      better among the participants compared with the refusers (P < 0.02) but there was
      no difference in the Dukes distribution when the test and control groups as a
      whole were compared. The number of adenomas in the two groups during seven years
      of follow-up was the same. CONCLUSION: The results indicate that screening and
      rescreening of a population has little influence upon the stage of the carcinomas
      in the test group compared with a control group during the first seven years of
      follow-up. The number of carcinomas was higher in the control than in the test
      group during the follow-up, probably because of a lead time effect during the
      screening.

PMID- 8306827
TI  - HSP90 associates with specific heat shock puffs (hsr omega) in polytene
      chromosomes of Drosophila and Chironomus.
AB  - The heat shock protein HSP90, which is mainly cytoplasmic, has recently been
      reported to be present in the nucleus. We have found a specific chromosomal
      localization of HSP90 in different species of Drosophila and Chironomus using
      immunocytochemical techniques with different mono- and polyclonal antibodies for
      this hsp. HSP90 was found associated with heat shock-induced puffs at 93D and 48B
      in salivary gland chromosomes of Drosophila melanogaster and Drosophila hydei,
      respectively. The localization of HSP90 to locus 93D occurred rapidly after the
      onset of heat shock and disappeared during recovery, concomitant with puff
      regression. The association of HSP90 with the 93D locus was strictly heat shock
      dependent as shown by the absence of HSP90 in puff 93D induced by either
      benzamide or colchicine. No specific nuclear staining was observed in unstressed
      control cells. HSP90 was also found in the temperature-induced telomeric Balbiani
      ring puffs (T-BRs) in Chironomus thummi and in one heat shock puff at I-1C in
      Chironomus tentans. Other heat shock puffs also appeared lightly stained with the
      HSP90 polyclonal antibody in both species of Chironomus. HSP90 was absent from
      the T-BRs when RNA synthesis was inhibited with Actinomycin D suggesting that the
      localization of HSP90 is dependent on transcription. Inhibition of protein
      synthesis did not prevent association of this hsp with the T-BRs, indicating that
      pre-existing HSP90 can associate with this locus. HSP90 did not associate with
      any telomeric chromosomal regions of unstressed cells. The present observations
      suggest that heat shock gene products such as HSP90 may somehow be involved in
      the regulation at the chromosomal level of other members of the heat shock gene
      family. Puffs 93D (D. melanogaster) and 48B (D. hydei) are equivalent and
      correspond to homologous gene loci (hsr omega) that have unusual features that
      distinguish them from other heat shock puffs. The binding of HSP90 at T-BRs and
      at puff I-1C in the genus Chironomus is the first demonstration, albeit indirect,
      of the existence of hsr omega analogous loci in species other than Drosophila.

PMID- 8306830
TI  - Stricture at the pouch-anal anastomosis after restorative proctocolectomy.
AB  - PURPOSE: The aim of this study was to determine what factors may be responsible
      for the development of a stricture at the pouch-anal anastomosis after
      restorative proctocolectomy. METHODS: A consecutive series of 115 patients was
      studied retrospectively a median of 34 months (range, 4-100 months) after
      operation or ileostomy closure. The procedure failed in 11 patients (9.6 percent)
      who subsequently had to have a permanent ileostomy. Another two patients were
      excluded from the analysis, one of whom was awaiting ileostomy closure, whereas
      the other had a stricture due to a desmoid tumor. Of the remaining 102 patients,
      39 (38 percent) developed an ileoanal anastomotic stricture, which was severe and
      persistent in 16 percent. RESULTS: The results were analyzed with the aid of
      multivariate logistic regression analysis. Factors which predisposed
      significantly to the development of an ileoanal anastomotic stricture were 1) use
      of the 25-mm (small) diameter stapling gun (P = 0.05), 3) use of a defunctioning
      ileostomy (P = 0.03), and 4) anastomotic dehiscence and pelvic sepsis (P = 0.03).
      The single patient whose operation failed because of a stricture had also
      developed pelvic sepsis associated with an anastomotic dehiscence. CONCLUSIONS:
      The eventual clinical, functional outcome after dilation of a stricture in the 39
      patients who developed a stricture was as good as the outcome in the 63 patients
      who did not a develop stricture.

PMID- 8306831
TI  - Five-year follow-up study of the fat clearance technique in colorectal carcinoma.
AB  - PURPOSE: The aim of our study was to determine the five-year survival of patients
      with colorectal carcinoma whose Dukes classification had changed following fat
      clearance of the mesocolon or mesorectum. METHODS: One hundred three patients
      with colorectal carcinoma were followed up at a special clinic for at least five
      years after surgery. The tumors from these patients had previously been given a
      Dukes classification before and after fat clearance. RESULTS: Four of the five
      patients whose Dukes status changed from B to C as a result of fat clearance died
      of malignant disease during the five-year follow-up period. After fat clearance
      it was apparent that Dukes B patients survived, on average, 11 months longer than
      Dukes C patients. A significantly increased mean number of positive nodes was
      found after fat clearance in Dukes C cases, both in those who were alive at five
      years and those who died of their malignant disease. CONCLUSIONS: The fat
      clearance technique is a useful aid to improving the accuracy of the Dukes
      classification and has prognostic significance. It should be used in specimens of
      colorectal carcinoma, which on initial examination appear to be Dukes B cases.

PMID- 8306832
TI  - Immunoscintigraphy with 111In-satumomab pendetide in patients with colorectal
      adenocarcinoma: performance and impact on clinical management.
AB  - PURPOSE: The role of immunoscintigraphy with 111In-satumomab pendetide in the
      medical and/or surgical management of colorectal cancer patients was evaluated in
      a multicenter trial. METHODS: This 103 patient study population included 46
      individuals with rising serum carcinoembryonic antigen levels and otherwise
      negative diagnostic evaluation, 29 patients with known recurrence, presumed to be
      isolated and resectable, and 28 patients for whom standard diagnostic tests
      provided equivocal information. RESULTS: No adverse reactions were noted
      following intravenous administration of 1 mg of satumomab pendetide radiolabeled
      with approximately 5 mCi of 111In. Thirty percent of patients developed human
      anti-mouse antibodies postinfusion. In the 84 patients for whom correlation with
      histopathologic, diagnostic, and/or clinical findings was available, antibody
      imaging demonstrated a sensitivity of 73 percent in patients with confirmed tumor
      (36/49) and negative results for all 35 patients with no evidence of malignancy.
      Occult disease was detected in 18 patients. CONCLUSION: 111In-satumomab pendetide
      immunoscintigraphy was helpful in the medical and/or surgical management of 45
      (44 percent) patients and provided information unavailable from other diagnostic
      modalities.

PMID- 8306833
TI  - Electromyography of the internal anal sphincter performed under endosonographic
      guidance. Description of a new method.
AB  - PURPOSE: The aim of our study was to investigate internal anal sphincter
      electromyographic signals. METHODS: Electromyography of the internal anal
      sphincter was performed with platinum wire electrodes in six healthy volunteers
      (three males and three females), inserted under endosonographic guidance.
      Platinum wire electrodes were also inserted into the external anal sphincter.
      Activity of both the internal and external and sphincter in a 40-second period
      was measured. RESULTS: Internal anal sphincter median activity was 22.1 (range,
      5.5-67.6) microV. Slow-wave activity was 47 cycles/minute (range, 34-55
      cycles/minute). After inflation of a rectal balloon with air until a constant
      relaxation of the anal canal was obtained, a decrease in internal and sphincter
      activity to 15.9 (1.2-31.3) microV as well as a decrease in slow-wave activity to
      34 cycles/minute (range, 27-40 cycles/minute) was found. The original internal
      anal sphincter EMG was resumed after deflation of the rectal balloon. External
      anal sphincter median activity was 3.1 (range, 0.77-18.6) microV. During
      inflation of the rectal balloon, a reflex increase in external sphincter EMG
      activity was found. With the rectal balloon fully inflated a part of this
      increase was still present, 11.0 (1.9-24.6) microV. In some of the subjects, this
      increased activity was superimposed on the internal anal sphincter recordings as
      well. During a voluntary squeeze it was not possible to identify internal anal
      sphincter activity due to activity of the external anal sphincter totally
      overriding the internal anal sphincter signal. CONCLUSION: Precise EMG recordings
      from the internal anal sphincter is possible with endosonographic guidance of the
      electrodes, except during voluntary squeezing of the external and sphincter.

PMID- 8306834
TI  - Surgical adjuvant therapy for rectal cancer: present options.
AB  - Recent advances have been made with the publication of the results of GITSG and
      NCCTG trials, which demonstrated the significant improvement of survival by
      combined postoperative radiochemotherapy protocols for Stage II and III rectal
      cancer. These data show that systemic chemotherapy has a decisive role to play in
      this policy. Some of the advantages of preoperative irradiation compared with
      postoperative radiation therapy consist of the improvement of resectability of T4
      tumors and the anal preservation for low-lying cancers. These data suggest that
      preoperative chemoradiotherapy should be applied not only to T4 tumors but also
      to all T3 tumors even when the transrectal extension is limited. The most usual
      protocol combines 5-fluorouracil (300-350 mg/m2/day) and leucovorin (20
      mg/m2/day) for 5 days, followed by radiation therapy (30-35 Gy in 10 fractions
      within 12-15 days), with surgery taking place 4 to 8 weeks later, after the tumor
      has been restaged. Systemic therapy is continued for four more months. T2 cancers
      should not be excluded from the benefit of preoperative irradiation.

PMID- 8306835
TI  - Laparoscopic-assisted colostomy closure after Hartmann's procedure.
AB  - PURPOSE: The aim of the study was to review our experience with colostomy closure
      after Hartmann's procedure and the possible impact of laparoscopic colostomy
      closure. METHODS: A retrospective review of hospital stay after colostomy closure
      by laparotomy in the last four years was conducted. A chart review of patients
      undergoing laparoscopic colostomy closure after Hartmann's procedure since the
      introduction of operative laparoscopy at our institution was also done. RESULTS:
      One hundred twenty patients had colostomy closure carried out by the trauma
      service at the University of Miami/Jackson Memorial Hospital. In thirty-seven
      patients, colostomy closure was associated with other surgical procedures such as
      ventral herniorrhaphy, delayed closure of the open abdomen, ureteroneocytostomy,
      and so forth, or they underwent loop colostomy closure. These patients were
      excluded from further review. Sixty-five patients underwent reversal of
      Hartmann's procedure by laparotomy. They had an average hospital stay of 9.5 days
      (range, 6 to 34 days). This group of patients had colostomy closure prior to the
      introduction of operative laparoscopy in our institution. With increased
      laparoscopy experience, laparoscopically assisted Hartmann's reversal has been
      attempted in 18 patients and completed in 14 patients. The average hospital stay
      in the laparoscopically completed group was 6.3 days (range, 4 to 10 days). This
      group had a 0 percent mortality and a 14.3 percent morbidity. This compares
      favorably to recently reported series of colostomy closure by laparotomy.
      CONCLUSION: Laparoscopically assisted Hartmann's reversal results in comparable
      morbidity, but may be associated with shorter hospital stay when compared with
      laparotomy.

PMID- 8306836
TI  - Positron emission tomography for preoperative staging of colorectal carcinoma.
AB  - PURPOSE: Positron emission tomography (PET) is an imaging technique based on in
      vivo cellular metabolism. Increased glucose metabolism in neoplastic cells is
      detected by using fluorine-18 deoxyglucose. In an ongoing pilot study to
      determine the usefulness of this technique, PET is compared with computerized
      tomography (CT) for the preoperative staging of colorectal carcinoma. METHODS:
      Sixteen patients were evaluated with both PET and CT of the abdomen and pelvis.
      Results were compared with operative and histopathologic findings. Fifteen
      malignant lesions were found in 16 patients by histology. PET had a positive
      predictive value of 93 percent and a negative predictive value of 50 percent. By
      comparison CT had a positive predictive value of 100 percent and a negative
      predictive value of 27 percent. CONCLUSIONS: These preliminary results indicate
      that PET has increased sensitivity for staging colorectal carcinoma, whereas CT
      has higher specificity. The predictive value of a positive PET compares favorably
      with CT. Furthermore, the predictive accuracy for detection of colorectal
      carcinoma is 83 percent for PET and 56 percent for CT.

PMID- 8306837
TI  - Results of ileal J-pouch-anal anastomosis in familial adenomatous polyposis
      complicated by rectal carcinoma.
AB  - PURPOSE: Rectal cancer frequently occurs in patients with familial adenomatous
      polyposis (FAP) and, in some cases, proctocolectomy and ileal pouch-anal
      anastomosis (IPAA) can be proposed as an alternative to end ileostomy. This study
      aimed to assess the results of IPAA for familial adenomatous polyposis
      complicated by rectal carcinoma. PATIENTS AND METHODS: Postoperative morbidity
      and bowel function following IPAA were assessed in six patients who had a
      mesorectal excision for rectal cancer. The functional results were compared with
      those obtained after IPAA in 134 FAP patients without bowel cancer. RESULTS:
      Carcinomas were located at a mean of 11 cm from the dentate line. There were no
      postoperative complications. One patient with synchronous hepatic metastases died
      6 months after operation and the 5 others were alive without recurrence after a
      mean follow-up of 29 months. Mean frequency of defecation was 6.5/day (vs.
      4.2/day in patients without carcinoma), 86 percent of patients had nocturnal
      defecation (vs. 50 percent), day and night continence were normal in 66 percent
      and 33 percent of patients, respectively, compared with 90 percent and 85 percent
      for IPAA without cancer. Pouch excision was required in one patient for
      unsatisfactory functional result. CONCLUSION: IPAA can be safely performed for
      cancer of the upper rectum complicating FAP, but a poor functional outcome
      related to mesorectal excision has to be expected.

PMID- 8306838
TI  - Treatment of fecal impaction with pulsed irrigation enhanced evacuation.
AB  - PURPOSE: A new method of treating fecal impaction is described, selecting
      patients that would otherwise have required operative disimpaction. METHOD: Using
      the pulsed irrigation enhanced evacuation device, individuals were selected for
      treatment based on evidence of massive fecal impaction on physical examination or
      abdominal x-ray. RESULTS: Fourteen individuals were treated for fecal impaction.
      The patients ranged in age from 13 to 86 years. Only one patient required
      intravenous sedation, an elderly patient with Alzheimer's disease. The treatment
      was successful in each case, although repeated treatment was often necessary. No
      morbidity arose from the treatment. By the midpoint in our study, because of the
      success of this treatment, no patient required hospitalization for impaction.
      CONCLUSION: Pulsed irrigation enhanced evacuation has been in our experience a
      simple, quick, and effective treatment for severe fecal impaction.

PMID- 8306839
TI  - Total pelvic exenteration for locally advanced rectal carcinoma.
AB  - Total pelvic exenteration was performed in 31 patients (30 males and 1 female)
      who had rectal cancers involving adjoining pelvic structures. Twenty-nine
      patients had primary tumors and two had recurrent diseases after previous
      abdominoperineal resection. Preoperative irradiation was used in nine patients
      with fixed tumors. When performing the surgical procedure, we also actively
      employed lateral node dissection to make the operation more radical. Three
      patients (one with primary tumor and two with recurrent) underwent the
      exenteration with partial sacrectomy because of the sacral involvement and they
      all died of local failure within 15 months. The overall 5-year survival rate was
      52 percent for all patients and 56 percent for those who had primary tumors. The
      results suggest that total pelvic exenteration with lateral node dissection
      should be performed for locally advanced rectal cancer if the tumor is not
      completely fixed to the pelvic wall and preoperative irradiation should be used
      to convert a fixed tumor to a resectable one.

PMID- 8306840
TI  - Colectomy in patients with inflammatory bowel disease and primary sclerosing
      cholangitis.
AB  - PURPOSE: The aim of this study was to assess risk factors for early postoperative
      death in patients with primary sclerosing cholangitis who are undergoing
      colectomy. METHODS: The charts of 24 patients with primary sclerosing cholangitis
      who underwent colectomy between 1972 and 1990 at the Cleveland Clinic Foundation
      were reviewed. Clinical and laboratory data were collected and compiled to
      determine preoperative factors that might be helpful in predicting early
      postoperative death. RESULTS: The only factor that predicted a poor outcome was
      cirrhosis at the time of surgery. Three of 8 patients with cirrhosis and 0 of 16
      patients without cirrhosis had an early postoperative death (P < 0.05, Fisher's
      exact test). CONCLUSION: We conclude that establishing whether or not patients
      with inflammatory bowel disease and primary sclerosing cholangitis have cirrhosis
      is helpful in determining the risk of colectomy.

PMID- 8306841
TI  - Endoscopic resection of large colorectal polyps using a clipping method.
AB  - PURPOSE: In conventional endoscopic snare polypectomy, bleeding and perforation
      are the principal concerns. To prevent these complications, we employ an
      endoscopic clipping technique using the HX-3L clipping apparatus. METHODS: With
      this method, clips are used to clamp the base of a polyp. A snare is hung
      peripheral to the clips. The polyp is then resected by coagulating and cutting
      with an electric current. RESULTS: Neither bleeding nor perforation during or
      after polypectomy has occurred, nor have complications related to the use of
      clips developed. Gigantic polyps were not resected piecemeal, but rather were
      resected en bloc facilitating a clear determination of cancer on the surface of
      the resected site. Endoscopic clipping permitted site marking for colonoscopic
      surveillance. CONCLUSION: We conclude that the clipping method has many
      advantages and is a useful technique in colonoscopic polypectomy.

PMID- 8306842
TI  - Prognostic value of the histochemical expression of helix pomatia agglutinin in
      advanced colorectal cancer. A univariate and multivariate analysis.
AB  - PURPOSE: The expression of helix pomatia agglutinin in advanced colorectal cancer
      was evaluated in order to determine whether helix pomatia agglutinin could serve
      as an effective prognostic indicator. METHODS: Using the histochemical procedure,
      the expression of helix pomatia agglutinin was studied in 117 patients with
      primary colorectal cancer. Sixty of 117 patients who died of either recurrence or
      metastasis within two years (Group 1) after resection were compared with the
      other 57 patients who survived for five years or longer (Group 2). RESULTS: The
      helix pomatia agglutinin-positive expression was seen in 34 cases of Group 1 and
      in only 15 cases of Group 2 (P < 0.01). Lymph node metastasis, lymphatic
      invasion, venous invasion, mucin production, and helix pomatia agglutinin
      expression all had a significant correlation with the prognosis in the univariate
      analysis; however, only lymph node metastasis, venous invasion, and helix pomatia
      agglutinin expression were prognostic factors with a significant difference in
      the multivariate analysis. CONCLUSIONS: Histochemical expression of helix pomatia
      agglutinin will indeed aid in accurately predicting the prognosis of patients
      with advanced colorectal cancer.

PMID- 8306843
TI  - Liver abscess after hemorrhoidectomy. Report of two cases.
AB  - PURPOSE: Pyogenic liver abscess after hemorrhoidectomy is extremely rare. Only
      two such cases have been previously reported; the diagnosis in each was made
      intraoperatively. We report two additional cases of hepatic abscess after
      hemorrhoidectomy, both treated nonoperatively with a successful outcome. METHODS:
      The two cases were analyzed for history, presentation, laboratory data,
      radiologic studies, and bacteriology. RESULTS: In both cases, the patients
      presented within one week of the hemorrhoidectomy. Treatment with broad-spectrum
      intravenous antibiotics was successful in achieving significant clinical
      improvement. The liver function test values reverted back to normal and follow-up
      computed tomography (CT) scans of the liver revealed marked improvement of the
      abscesses. Laparotomy was avoided in both of the patients. CONCLUSIONS: Increased
      awareness of this serious complication will afford earlier diagnosis. In
      addition, proper aerobic and anaerobic bacterial isolation techniques will allow
      appropriate nonoperative therapy, decreasing the high morbidity and mortality
      rates associated with this complication.

PMID- 8306844
TI  - Efficient technique for retrieving small polyps from the colon and rectum
      following snare polypectomy.
AB  - The use of a 4- x 4-inch gauze pad at the suction port during snare colonoscopic
      polypectomy facilitates the retrieval of polyps. This technique is a simple,
      rapid, and cost-effective method of retrieving small polyps for pathologic
      evaluation.

PMID- 8306845
TI  - The laparoscope: an excellent illumination tool for deep pelvic dissection.
AB  - Adequate illumination during deep pelvic dissection in low anterior resection and
      abdominoperineal resection is sometimes difficult and frustrating, especially in
      deep narrow pelvises. Various methods of illumination are being used to overcome
      this problem. We present our technique of using the laparoscope as an excellent
      illumination tool for deep pelvic dissection in conventional surgery.

PMID- 8306846
TI  - Acute and chronic presentation of intestinal nonrotation in adults.
AB  - Intestinal nonrotation has been recognized as a cause of obstruction in neonates
      and children and may be complicated by volvulus and intestinal necrosis. It is
      very rarely seen in the adult and may present acutely as a bowel obstruction and
      intestinal ischemia associated with midgut or ileocecal volvulus, or chronically
      as vague intermittent abdominal pain. The purpose of this communication is to
      reveal the pathogenesis and the surgical significance of intestinal nonrotation
      in adults and to review the English and German language literature since 1923 to
      establish the optimal therapeutic management. Between 1983 and 1992, we have
      managed and observed prospectively 10 adults with intestinal nonrotation. In four
      patients the nonrotation has been detected at emergency laparotomy owing to
      midgut or ileocecal volvulus. Four patients suffered from chronic symptoms of
      intermittent volvulus or small bowel obstruction and in two patients the
      nonrotation has been noted as an incidental finding at laparotomy for another
      condition. A survey of the literature from 1923 to 1992 revealed 40 adults with
      symptomatic intestinal nonrotation to which we contribute nine patients. We
      establish that in the acute symptomatic pattern, only emergency laparotomy can
      provide the correct diagnosis and decrease the risk of bowel disturbance. In the
      chronic situation, barium studies of the upper and lower gastrointestinal tract
      reveal varying degrees of midgut malrotation and confirm the nonrotation in each
      case. Also, in these forms the explorative laparotomy with a consequent staging
      of the abdominal situs is to be recommended. All reported cases at our
      institutions are without complaints after surgery. Adult patients with intestinal
      nonrotation and acute or chronic obstructive symptoms or those detected
      incidentally at laparotomy for other conditions should undergo a Ladd procedure
      because of the risk of midgut volvulus. In this operation, the nonrotation is
      left in place and the ascending colon is sutured at the colon descendens and
      sigmoideum. After this procedure the mesenteric pedicle is fixed and the risk of
      midgut torsion remains minimal.

PMID- 8306847
TI  - Cardiac pearls.
AB  - Most diagnoses of cardiovascular disease are made in the office or at the
      bedside. For example, in pulsus alternans of the radial pulse, observed when
      first greeting a patient, alteration of intensity of the second sound and
      systolic murmur and a ventricular (S3) gallop are clinical pearls--often subtle-
      that diagnose cardiac decompensation. A faint gallop, ventricular (S3) or atrial
      (S4), might be overlooked in a patient who has an emphysematous chest and an
      increase in anteroposterior diameter if one listens over the usual areas of the
      precordium. However, the gallop might be detected easily by listening over the
      xiphoid or epigastric area. How do you tell the difference between an S4, a split
      first sound, and an ejection sound? The S4 is eliminated with pressure on the
      stethoscope, but pressure does not eliminate the ejection sound or the splitting
      of S1. The atrial sound (S4) is most frequently found in patients who have
      coronary heart disease, and it is a constant finding in patients who have
      hypertension. It does not denote heart failure, as does the S3 (ventricular)
      gallop. In some patients, both atrial (S4) and ventricular (S3) diastolic gallops
      may be present. This occurrence is common in patients with cardiac decompensation
      associated with coronary heart disease, hypertensive heart disease, and dilated
      cardiomyopathy. When these diastolic filling sounds occur in close proximity, a
      short rumbling murmur may be heard, which causes confusion of this sound with
      that of a valvular or congenital lesion. When both sounds occur exactly
      simultaneously, a single sound results. Often, this sound is louder than either
      the first or second sound and can be misinterpreted as either a valvular or
      congenital lesion. This, however, is a summation gallop, which is rare. For the
      most accurate timing of heart sounds and murmurs, the simple technique called
      "inching" is the best. Keeping the second sound in mind as a reference, the
      physician moves (inches) the stethoscope from the aortic area to the apex. An
      extra sound may be noted to occur in systole before the second sound, thereby
      diagnosing a systolic click. If the sound occurs after the second sound, however,
      it is an S3 or ventricular diastolic gallop. If a murmur appears before S2, it is
      a systolic murmur; if it appears after S2, it is a diastolic murmur. When the
      Austin-Flint murmur is heard, significant aortic regurgitation exists.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8306848
TI  - Women, contraception and HIV.

PMID- 8306849
TI  - Medical indications for childhood circumcision.

PMID- 8306850
TI  - New terms for the pharmaceutical price regulation scheme.

PMID- 8306851
TI  - [One session diagnostic heart catheterization and balloon dilatation ("prima
      vista"-PTCA): results and risks].
AB  - Percutaneous transluminal coronary angioplasty (PTCA) immediately after elective
      diagnostic cardiac catheterization ("prima vista"-PTCA) was performed in 124
      patients (group 1) with typical angina pectoris (96 men, 28 women; mean age 60 +/
      10 [25-86] years). In a case-control analysis the results and complications, as
      well as the volume of contrast media and amount of radiation exposure were
      compared with a group of patients with similar symptoms (group 2) who during the
      same period had undergone angiography at another hospital and subsequently PTCA
      in our department (96 men, 28 women; mean age 60 +/- 8 [39-78] years). The
      success rate in group 1 (122 of 138 stenoses: 92.1%) was similar to that in group
      2 (122 of 138 stenoses: 88.4%). Complications (coronary artery dissection with
      occlusion, emergency operation, myocardial infarction) were rare in both groups
      (8 vs 5; difference not significant). But the combined procedure (group 1) used
      lower volumes of contrast medium (341 +/- 131 vs 250 +/- 113 ml; P < 0.001) and
      the cumulative fluoroscopic time was lower (33.7 +/- 19.5 vs 26.5 +/- 12.4 min; P
      < 0.002). With optimal logistic conditions, "prima vista"-PTCA under elective
      circumstances is a useful and patient-friendly alternative to the conventional
      two-session diagnostic and therapeutic procedures.

PMID- 8306852
TI  - [Neurocysticercosis].
AB  - A 49-year-old woman from Croatia, resident in Switzerland for 22 years, had a
      history of headaches and arterial hypertension for 8 years. While in hospital for
      assessment and treatment she developed focal seizures. She had an eosinophilia
      (10%) and computed tomography of the skull demonstrated cysts and multiple
      calcified foci in the left cerebral hemisphere. Antibodies against Taenia solium
      antigen were found in both serum and cerebrospinal fluid. Anthelminthic treatment
      with albendazole (15 mg/kg daily for 25 days) and anticonvulsive treatment with
      phenytoin (serum levels between 10 and 20 mg/l) markedly improved the symptoms
      and the cysts regressed. Neurocysticercosis, caused by the larvae of the pork
      tapeworm, is occurring even more frequently because of the migration of people
      from countries where the disease is endemic.

PMID- 8306853
TI  - [Bilateral massive macronodular adrenal gland hyperplasia. A rare cause of
      Cushing's syndrome].
AB  - A 46-year-old man with known arterial hypertension for 10 years had, over the
      last two years, developed increasing obesity, particularly of the trunk, with
      other symptoms typical of Cushing's syndrome. Hormone analysis demonstrated
      hypercortisolism and decreased plasma ACTH concentration. The dexamethasone
      inhibition test failed to show any significant suppression of serum cortisol.
      Plasma ACTH was not increased in the corticotrophin-releasing hormone and the
      metyrapone tests. In the short ACTH test there was an excessive cortisol
      increase. Abdominal computed tomography revealed both adrenals to be enlarged (6
      x 4 cm) and coarsely nodular. Adrenolytic treatment with ketoconazole (400 mg
      daily) caused symptoms of adrenal insufficiency, but a reduced dosage of 200 mg
      daily lowered the cortisol level to between 5 and 11 micrograms/dl and normalized
      the blood pressure and clinical signs of Cushing's syndrome disappeared.
      Subsequent bilateral adrenalectomy confirmed the diagnosis of massive
      macronodular adrenal hyperplasia. Substitution treatment with twice daily 25 mg
      cortisone acetate and 0.05 mg fludrocortisone was started postoperatively.

PMID- 8306854
TI  - [Indications for and use of home artificial respiration].

PMID- 8306855
TI  - [Munchausen syndrome].

PMID- 8306856
TI  - [Theodor Billroth on the 100th anniversary of his death].

PMID- 8306857
TI  - [Criticism of the Association of National Health Program Physicians and freedom
      of speech. Decision of the Federal Constitution Court on September 24, 1993].

PMID- 8306859
TI  - [Computed tomography guided fine needle biopsy].

PMID- 8306858
TI  - [Dental alloys].

PMID- 8306860
TI  - Studies on the prevalence of Eubacterium suis in boars on farms in Brazil,
      Portugal and Argentina by indirect immunofluorescence technique.
AB  - The main habitat of Eubacterium suis (E. suis) is the preputial diverticulum of
      male pigs. E. suis can be transmitted from boars to the vestibule of sows at the
      time of mating and ascending urinary tract infections in sows may result. A total
      of 195 swabs of the preputial diverticulum was collected for prevalence studies
      of E. suis infections in adult breeding males on Brazilian (n = 96 boars),
      Portuguese (n = 78 boars) and Argentinian (n = 21 boars) farms. The fixed smears
      were stored at 4 degrees C for one to four months until indirect
      immunofluorescence test was performed. Eubacterium suis was found in 75 (78%), 52
      (67%) and 16 (76%) boars, respectively. These results indicate that E. suis is
      present in Brazil, Argentina as well as in Portugal and may be involved in
      urinary tract infections of sows more frequently as it is known till now.

PMID- 8306861
TI  - [Helicobacter pylori: studies in domestic swine].
AB  - In the course of 15 month, 240 stomachs from pigs slaughtered in three different
      slaughterhouses were examined for the presence of Helicobacter pylori. In 52.5%
      of the stomachs, gram-negative curved or spiral shaped bacteria were found, which
      during the following biochemical analyses were demonstrated to be urease
      negative. Helicobacter pylori could not be isolated from any of the stomachs. In
      addition, we conducted four separate experiments on five to eight weeks old
      piglets in order to determine whether they could be infected by the germ. In the
      first experiment, the piglets were starved for 24 hours and then driven for five
      minutes, before an elevated dose of Helicobacter pylori-germs was administrated
      orally. In the second experiment, acetylsalicylic acid, which is known to damage
      the stomach lining, was given, even on a damaged mucosa, a dose of 5 x 10(9)
      living germs could not provoke an infection by Helicobacter pylori. In the third
      experiment the piglets were given cimetidine, which reduces the production of
      stomach acid. This measure was presumed to facilitate the penetration of
      Helicobacter pylori from the stomach cavity underneath the protective mucus. The
      administration of Helicobacter pylori following the cimetidine-medication proved
      to be unsuccessful. In addition to culturing and the biochemical analyses
      employed in the three afore mentioned experiments, the fourth experiment included
      the identification of the germ means of a breath-analyzing test (with 13C-urea),
      as is used in medical diagnosis of helicobacteriosis. In these pigs too,
      infection with Helicobacter pylori was unsuccessful.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8306862
TI  - [Causes of mortality in a swine breeding establishment].
AB  - Preweaning losses: During the period from September 1991 to August 1992, from
      18021 piglets born alive 3417 died until weaning. Major causes of death were
      crushing by the sow, low birth weight, starvation, splay-leg disease and
      enteritis. Of these animals 51.6% died during the first three days of life.
      Mortality decreased during the preweaning period. Litters with more than 11 pigs
      had elevated death rates of piglets. Mortality was higher during the cold season
      (except January). Postweaning losses: During the postweaning period 6.4% of the
      weaned piglets were lost. Of these piglets 4.1% died and the remaining 2.3% were
      sold due to umbilical hernia. Diseases of the gastrointestinal tract were the
      main cause of death. Losses of gilts: During the one-year surveillance period 373
      gilts were lost. Most of 18 deceased animals died from bleeding due to gastric
      ulcers and from purulent bronchopneumonia. 314 (91.1%) of the remaining 355 gilts
      were sold, the residual 9.9% of the animals were slaughtered mainly because of
      diseases of the musculoskeletal system. Losses of sows: In the breeding herd of
      950 to 1035 animals, 35 sows died and 492 were culled in the course of one year.
      Most deaths resulted from cardiac failure and splenic torsion. Urogenital and
      locomotor diseases were the main reason for culling. The sows removed from the
      herd had produced an average of 3.6 litters, but 52.8% had produced no more than
      3 litters. Losses of boars: During the survey 10 boars were slaughtered.

PMID- 8306863
TI  - Investigations on dietary treatment of struvite urolithiasis: 3. Effect of an
      acidifying diet on acid-base- and mineral-balance of cats after acute urethral
      obstruction.
AB  - The effect of a commercial acidifying diet on acid-base-balance and urinary
      mineral concentration was compared in five healthy cats and five cats with
      urethral obstruction for six days after the removal of lower urinary tract
      obstruction. There were no significant differences in urine pH throughout the
      experiment between the groups. Blood pH was decreased in obstructed animals at
      the time of presentation at the clinic, but thereafter it did not differ from
      data from healthy cats on the same diet. The concentration of phosphorus and
      potassium in urine decreased, sodium and chloride did not change, while magnesium
      and calcium content increased.

PMID- 8306864
TI  - [Cryopreservation trial with semen of purebred Arabian and Haflinger stallions in
      the Turkish national stud in Karacabey].
AB  - Within a German-Turkish university partnership deep freezing preservation of
      stallion semen was performed as a part project of the cooperation contract. In
      this study a modification of the introduced Makrotub method was used for semen
      freezing. The investigated characteristics of fresh semen of the Arab stallions
      were in the normal range cited in the international literature. However, the
      semen data obtained from the Haflinger stallions were markedly and partially
      significantly in lower range than measured for the Arab stallions. This may
      reflect an incomplete adaptation process of the imported Haflinger horse
      population. Local circumstances did not allow Al trials.

PMID- 8306865
TI  - [The epizootiology of BVD virus infections in Hessian dairy cattle stock].
AB  - Clinical manifestation and course of disease caused by BVD virus infection in 77
      BVD-infected dairy cattle stocks in Middle Hessia are described. In 17 herds,
      serological and virological status of the animals was determined, and the results
      of an eradication program based on vaccination were evaluated. In animals with
      mucosal disease, a decrease in typical mucosal and interdigital lesions and an
      increase in respiratory symptoms with emaciation and a less specific pattern of
      disease could be observed.

PMID- 8306866
TI  - [Reported frequency of dermatophytes in cats and dogs in Austria].
AB  - During four years (1988-1991) 384 skin scrapings and hair samples obtained from
      cats and 636 samples obtained from dogs in Austria were examined routinely for
      dermatophytes. In cats dermatophytes were isolated or found positive in unstained
      KOH preparation in 50.3% of the samples. 90.7% of these cats were proved to be
      infected with Microsporum canis. Trichophyton mentagrophytes was isolated in 5.2%
      and Trichophyton spp. in 2.1% of the positive samples. In dogs dermatophytes were
      isolated from 12.4% of the samples. 58.2% of the dermatophyte positive dogs were
      found to be infected with M. canis. Trichophyton mentagrophytes and Trichophyton
      spp. were isolated more frequently (19.0% and 7.6% of the positive samples) than
      in cats. In 13.9% of the positive samples hyphae and/or ectothrix spores could be
      found but culturing was negative.

PMID- 8306867
TI  - [Different effects of homeopathic potencies and conventional dilutions on
      specific liver enzymes of rats--an in vivo study].
AB  - It was searched for differing effects of homeopathic potencies and equally
      concentrated conventional dilutions. Activities of enzymes from three different
      subcellular compartments of the rat liver served as parameters for the
      evaluation. Especially in the D15/10(-15) range differences proved to be
      statistically relevant. The series with potentiated carrier substance, necessary
      from heuristic reasons and related to the homeopathic potencies, resulted in
      hitherto not understandable findings.

PMID- 8306869
TI  - [Establishment of vaccination schedules for protective levels of vaccines for the
      control of Aujeszky's disease in breeding stock].
AB  - In this study the influence of vaccination frequency on its efficacy was
      investigated using a computer model. Previous investigations in sow breeding
      stocks revealed a number of animals with low or without antibody titers despite
      the official recurrent vaccination procedure. The simulation study aimed at
      proving the assumption that the gaps in immuno protection were caused by the
      exclusion of certain stages of pregnancy from vaccination, as required on the
      product label. The non-vaccination of sows in early or late stages of pregnancy
      or of suckling sows results in gaps of protection which take long periods to
      diminish. Additionally, the introduction of unvaccinated gilts or boars and re
      breeding sows delay this process, resulting in the constant presence of some
      unprotected single animals in the population. The study shows that a management
      procedure with five vaccinations per year is able to close the gaps even with the
      required exclusion of animals in certain reproduction stages. The only
      alternative would be to vaccinate all individuals of the stock in one cycle
      regardless to their stage of pregnancy or lactation. This however seems to be
      impracticable in the field. The model clearly indicates one of the reasons why
      the eradication of pseudorabies has not yet succeeded.

PMID- 8306868
TI  - [Toxin-producing pasteurellas in a cattle herd].
AB  - Besides other agents, indole-negative Pasteurellae, producing dermonecrotic
      Pasteurella toxin, were isolated from the noses of calves in a herd with enzootic
      bronchopneumonia. In some blood sera, antitoxin was detected. According to their
      biochemical activities, isolated strains were classified as P. multocida ssp.
      septica (ornithine-negative), P. avium (biovar 2), and P. canis (biovar 2).
      However, in DNA-DNA hybridisation tests there was much coincidence with P.
      multocida. In experimental calves, pneumonic lesions were produced with one of
      the isolates as well as with the dermonecrotic toxin. Therefore, indole negative
      toxinogenic Pasteurellae are considered pneumonia causing agents. They should be
      taken into account in bacteriological diagnostic and for production of herd
      specific bacterins.

PMID- 8306870
TI  - A case of atresia ani with rectovestibular fistulae in an alpaca (L. pacos).
AB  - This communication reviews the generally accepted embryological development of
      rectovestibular fistulae and describes in detail, the diagnostic procedures and
      clinical findings of this condition in an alpaca (L. pacos). Specific modalities
      are detailed which facilitate this diagnosis in an animal with atresia ani.
      Comments are also directed to the incidence, reporting, and documentation of this
      and related conditions in South American camelids.

PMID- 8306871
TI  - Expression of the c-ret proto-oncogene during mouse embryogenesis.
AB  - The c-ret proto-oncogene encodes a receptor tyrosine kinase whose normal function
      has yet to be determined. To begin to investigate the potential role of this gene
      in vertebrate development, we have isolated cDNA clones representing the murine c
      ret gene, and have analyzed the pattern of expression during mouse embryogenesis,
      using northern blotting, in situ hybridization to histological sections and whole
      mount hybridization histochemistry. c-ret transcripts were detected beginning at
      day 8.5 of embryogenesis, and were observed in a number of cell lineages in the
      developing peripheral and central nervous systems, as well as in the excretory
      system. In the cranial region at day 8.5-9.5, c-ret mRNA was restricted to a
      population of neural crest cells migrating from rhombomere 4 and forming the
      anlage of the facioacoustic ganglion, as well as to a closely associated domain
      of surface ectoderm and pharyngeal endoderm. At later stages (10.5-14.5 days), c
      ret mRNA was observed in all cranial ganglia. In the peripheral nervous system of
      the trunk, c-ret was expressed in the autonomic ganglia and in subsets of cells
      in the dorsal root ganglia. In the enteric nervous system, c-ret was expressed in
      the presumptive enteric neuroblasts of the vagal crest (day 9.0-11.5), and in the
      myenteric ganglia of the gut (day 13.5-14.5). c-ret mRNA was observed in several
      regions of the central nervous system, including the undifferentiated
      neuroepithelial cells of the ventral neural tube (8.5 days), the motor neurons in
      the spinal cord and the hindbrain (10.5-14.5 days), the embryonic neuroretina
      (day 13.5) and the layers of the postnatal retina containing ganglion, amacrine
      and horizontal cells. Outside the nervous system, c-ret was expressed in the
      nephric (Wolffian) duct at day 8.5-10.5, the ureteric bud epithelium (but not the
      surrounding metanephric mesenchyme) at day 11.0-11.5, and the growing tips of the
      renal collecting ducts (but not the previously formed, subcortical portions of
      the collecting ducts, or the mesenchyme-derived renal vesicles) at day 13.5-17.5.
      Our results suggest that the c-ret gene may encode the receptor for a factor
      involved in the proliferation, migration, differentiation or survival of a
      variety of neuronal cell lineages, as well as in inductive interactions during
      organogenesis of the kidney.

PMID- 8306872
TI  - glp-1 can substitute for lin-12 in specifying cell fate decisions in
      Caenorhabditis elegans.
AB  - Members of the lin-12/Notch gene family encode receptors for intercellular
      signals and are found throughout the animal kingdom. In many animals, the
      presence of at least two lin-12/Notch genes raises the issue of the significance
      of this duplication and divergence. In Caenorhabditis elegans, two lin-12/Notch
      genes, lin-12 and glp-1, encode proteins that are 50% identical, with different
      numbers of epidermal growth factor-like motifs in their extracellular domains.
      Many of the cell fate decisions mediated by lin-12 and glp-1 are distinct. Here,
      we express glp-1 protein under the control of lin-12 regulatory sequences in
      animals lacking endogenous lin-12 activity and find that glp-1 can substitute for
      lin-12 in mediating cell fate decisions. These results imply that the lin-12 and
      glp-1 proteins are biochemically interchangeable, sharing common ligand and
      effector proteins, and that the discrete lin-12 and glp-1 mutant phenotypes
      result from differential gene expression. In addition, these results suggest that
      the duplicate lin-12/Notch genes found in vertebrates may also be biochemically
      interchangeable.

PMID- 8306873
TI  - Activity and expression pattern of cyclin-dependent kinase 5 in the embryonic
      mouse nervous system.
AB  - Cyclin-dependent kinase 5 (cdk5) was originally isolated on the basis of its
      close primary sequence homology to the human cdc2 serine/threonine kinase, the
      prototype of the cyclin-dependent kinases. While kinase activities of both cdc2
      and cdk2 are detected in proliferating cells and are essential for cells to
      progress through the key transition points of the cell cycle, cdk5 kinase
      activity has been observed only in lysates of adult brain. In this study, we
      compared the activity and expression of cdk5 with that of cdc2 and cdk2 in the
      embryonic mouse forebrain. The expression and activity of cdk5 increased
      progressively as increasing numbers of cells exited the proliferative cycle. In
      contrast, the expression and activity of cdc2 and cdk2 were maximum at
      gestational day 11 (E11) when the majority of cells were proliferating and fell
      to barely detectable levels at E17 at the end of the cytogenetic period.
      Immunohistochemical studies showed that cdk5 is expressed in postmitotic neurons
      but not in glial cells or mitotically active cells. Expression of cdk5 was
      concentrated in fasciculated axons of postmitotic neurons. In contrast to other
      cell division cycle kinases to which it is closely related, cdk5 appears not to
      be expressed in dividing cells in the developing brain. These observations
      suggest that cdk5 may have a role in neuronal differentiation but not in the cell
      division cycle in the embryonic nervous system.

PMID- 8306874
TI  - The developing organ of Corti contains retinoic acid and forms supernumerary hair
      cells in response to exogenous retinoic acid in culture.
AB  - The mammalian organ of Corti has one of the most highly ordered patterns of cells
      in any vertebrate sensory epithelium. A single row of inner hair cells and three
      or four rows of outer hair cells extend along its length. The factors that
      regulate the formation of this strict pattern are unknown. In order to determine
      whether retinoic acid plays a role during the development of the organ of Corti,
      exogenous retinoic acid was added to embryonic mouse cochleae in vitro. Exogenous
      retinoic acid significantly increased the number of cells that developed as hair
      cells and resulted in large regions of supernumerary hair cells and supporting
      cells containing two rows of inner hair cells and up to 11 rows of outer hair
      cells. The effects of retinoic acid were dependent on concentration and on the
      timing of its addition. Western blot analysis indicated that cellular retinoic
      acid binding protein (CRABP) was present in the sensory epithelium of the
      embryonic cochlea. The amount of CRABP apparently increased between embryonic day
      14 and postnatal day 1, but CRABP was not detectable in sensory epithelia from
      adults. A retinoic acid reporter cell line was used to demonstrate that retinoic
      acid was also present in the developing organ of Corti between embryonic day 14
      and postnatal day 1, and was also present in adult cochleae at least in the
      vicinity of the modiolus. These results suggest that retinoic acid is involved in
      the normal development of the organ of Corti and that the effect of retinoic acid
      may be to induce a population of prosensory cells to become competent to
      differentiate as hair cells and supporting cells.

PMID- 8306875
TI  - Basic fibroblast growth factor induces differentiation of neural tube and neural
      crest lineages of cultured ectoderm cells from Xenopus gastrula.
AB  - The vertebrate nervous system is initially induced from a section of dorsal
      ectoderm by signal(s) from the underlying dorsal mesoderm during gastrulation. In
      an effort to identify the neural inducing factor(s) emanating from the dorsal
      mesoderm, we have examined the inductive action of various growth factors by
      applying them to ectoderm cells from Xenopus gastrulae (8- to 12.5-hour age;
      embryonic stage 9+ to 11 1/2) in a microculture system. Monoclonal antibodies
      that specifically recognize cellular differentiation antigens from three distinct
      ectoderm lineages (N1 for CNS neurons from neural tube, Me1 for melanophores from
      neural crest and E3 for skin epidermal cells from epidermal lineages,
      respectively) and a mesoderm lineage (Mu1 for muscle cells) were used as markers
      to monitor the differentiation of cultured ectoderm cells. We found that basic
      fibroblast growth factor (bFGF) was capable of specifically and reproducibly
      inducing gastrula ectoderm cells to produce CNS neurons and melanophores at
      concentrations as low as 5 pM, a value about 50-fold lower than that required to
      induce the formation of muscle cells from blastula animal cap cells (6-hour age;
      stage 8+). The induction of neural lineages by bFGF was correlated with a
      suppression of epidermal differentiation in a dose-dependent manner. bFGF never
      induced the formation of muscle cells from gastrula ectoderm cells even at
      concentrations as high as 5 nM. The response of ectoderm cells to bFGF changed
      dramatically during gastrulation. Ectoderm cells from early (8- to 9-hour age;
      stage 9+ to 10) gastrula gave rise to CNS neurons, but yielded few melanophores.
      As ectoderm cells were prepared from gastrulae of increasing age, their
      competence to form neurons was gradually lost, whereas the production of
      melanophores was enhanced and peaked in 11-hour gastrula (stage 10 1/2). The
      ability to form both neurons and melanophores was substantially reduced in 12.5
      hour gastrula (stage 11 1/2). By examining ectoderm cells from the ventral and
      dorsal sides independently, it was also shown that during gastrulation the change
      in response to bFGF of the ventral ectoderm preceded that of the dorsal ectoderm.
      The state of competence of the ectoderm changed primarily due to intrinsic
      factors rather than by instruction from other parts of the gastrula embryo. This
      was shown by adding bFGF to cultures of ectoderm cells that were isolated at 9
      hour (stage 10) and cultured for increasing periods to allow their autonomous
      development. The time course of both loss of neuronal competence and gain and
      loss of melanophore competence closely paralleled that observed in vivo during
      gastrulation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8306876
TI  - Defects in mesoderm, neural tube and vascular development in mouse embryos
      lacking fibronectin.
AB  - To examine the role of fibronectin in vivo, we have generated mice in which the
      fibronectin gene is inactivated. Heterozygotes have one half normal levels of
      plasma fibronectin, yet appear normal. When homozygous, the mutant allele causes
      early embryonic lethality, proving that fibronectin is required for
      embryogenesis. However, homozygous mutant embryos implant and initiate
      gastrulation normally including extensive mesodermal movement. Neural folds also
      form but the mutant embryos subsequently display shortened anterior-posterior
      axes, deformed neural tubes and severe defects in mesodermally derived tissues.
      Notochord and somites are absent; the heart and embryonic vessels are variable
      and deformed, and the yolk sac, extraembryonic vasculature and amnion are also
      defective. These abnormalities can be interpreted as arising from fundamental
      deficits in mesodermal migration, adhesion, proliferation or differentiation as a
      result of the absence of fibronectin. The nature of these embryonic defects leads
      to reevaluation of suggested roles for fibronectin during early development based
      on results obtained in vitro and in embryos of other species.

PMID- 8306877
TI  - The expression of a zebrafish gene homologous to Drosophila snail suggests a
      conserved function in invertebrate and vertebrate gastrulation.
AB  - Snail, a zinc finger protein, is required for the formation of the ventral furrow
      and the mesoderm during gastrulation of the Drosophila embryo. snail homologues
      have been cloned from Xenopus and mouse. We have isolated a zebrafish homologue
      of snail, designated sna-1. Like its Drosophila counterpart, Sna-1 protein is
      nuclear. Maternal and zygotic sna-1 transcripts are ubiquitously distributed in
      zebrafish embryos of cleavage and blastula stages. In gastrulating embryos, sna-1
      is expressed in involuting cells of the germ ring, but not in those at the dorsal
      midline, the presumptive notochordal region. After involution, the expression is
      maintained in the paraxial mesoderm and becomes prominent in the muscle pioneer
      precursors, followed by expression at the posterior somite boundaries. Later, sna
      1 is expressed in neural crest and mesodermal derivatives of the head region. Sna
      1 expression is induced in animal cap cells by activin A. The early sna-1
      expression pattern in gastrulating zebrafish no tail (ntl) mutant embryos is
      normal except a reduction in the level of sna-1 transcription, suggesting that
      Ntl protein is not the key activator of sna-1 transcription in vivo, but might be
      involved in the enhancement or maintenance of sna-1 transcription. Data obtained
      in studies with ectopic ntl expression support this model.

PMID- 8306878
TI  - Variable and multiple expression of Protease Nexin-1 during mouse organogenesis
      and nervous system development.
AB  - Protease Nexin-1 (PN-1) also known as Glia-Derived Nexin (GDN) inhibits the
      activity of several serine proteases including thrombin, tissue (tPA)- and
      urokinase (uPA)-type plasminogen activators. These and other serine proteases
      seem to play roles in development and tissue homeostasis. To gain insight into
      where and when PN-1 might counteract serine protease activities in vivo, we
      examined its mRNA and protein expression in the mouse embryo, postnatal
      developing nervous system and adult tissues. These analyses revealed distinct
      temporal and spatial PN-1 expression patterns in developing cartilage, lung,
      skin, urogenital tract, and central and peripheral nervous system. In the
      embryonic spinal cord, PN-1 expression occurs in cells lining the neural canal
      that are different from the cells previously shown to express tPA. In the
      developing postnatal brain, PN-1 expression appears transiently in many neuronal
      cell populations. These findings suggest a role for PN-1 in the maturation of the
      central nervous system, a phase that is accompanied by the appearance of
      different forms of PN-1. In adults, few distinct neuronal cell populations like
      pyramidal cells of the layer V in the neocortex retained detectable levels of PN
      1 expression. Also, mRNA and protein levels did not correspond in adult spleen
      and muscle tissues. The widespread and complex regulation of PN-1 expression
      during embryonic development and, in particular, in the early postnatal nervous
      system as well as in adult tissues suggests multiple roles for this serine
      protease inhibitor in organogenesis and tissue homeostasis.

PMID- 8306879
TI  - A role for the mesoderm in endodermal migration and morphogenesis in Drosophila.
AB  - The endodermal midgut arises from two primordia, the anterior midgut (AMG)
      primordium and the posterior midgut (PMG) primordium, which are separated by
      almost the entire length of the Drosophila embryo. To form the midgut, these two
      parts have to extend towards each other and to fuse laterally on both sides of
      the yolk. Shortly before and during that movement, AMG and PMG are arranged as
      mesenchymal cell masses, but later the midgut cells form an epithelium. We show
      that these two aspects of midgut development, migration of AMG and PMG and
      transition to an epithelium, depend on the mesoderm. The extension of the midgut
      primordia is achieved by cell migration along the visceral mesoderm which forms a
      continuous layer of cells within the germ band. In mutant embryos lacking the
      entire mesoderm or failing to differentiate the visceral mesoderm, AMG and PMG
      are formed but do not migrate properly. In addition, they fail to form an
      epithelium and instead either remain as compact cell masses anterior and
      posterior to the yolk (in twist and snail mutant embryos) or only occasionally
      wrap around the yolk before embryogenesis is completed (in tinman-deficient
      embryos). We conclude that the visceral mesoderm serves as a substratum for the
      migrating endodermal cells and that the contact between visceral mesoderm and
      endoderm is required for the latter to become an epithelium.

PMID- 8306880
TI  - Xwnt-11: a maternally expressed Xenopus wnt gene.
AB  - We have isolated and characterized a novel Xenopus wnt gene, Xwnt-11, whose
      expression pattern and overexpression phenotype suggest that it may be important
      for dorsal-ventral axis formation. Xwnt-11 mRNA is present during oogenesis and
      embryonic development through swimming tadpole stages. Xwnt-11 mRNA is ubiquitous
      in early oocytes and is localized during mid-oogenesis. By late oocyte stages,
      Xwnt-11 mRNA is localized to the vegetal cortex, with some mRNA in the vegetal
      cytoplasm. After egg maturation, Xwnt-11 mRNA is released from the vegetal cortex
      and is found in the vegetal cytoplasm. This early pattern of Xwnt-11 mRNA
      localization is similar to another vegetally localized maternal mRNA, Vg1 (D. A.
      Melton (1987) Nature 328, 80-82). In the late blastula, Xwnt-11 mRNA is found at
      high levels in the dorsal marginal zone. As gastrulation proceeds, Xwnt-11 mRNA
      appears in the lateral and ventral marginal zone and, during tadpole stages, it
      is found in the somites and first branchial arch. Injection of Xwnt-11 mRNA into
      UV-ventralized embryos can substantially rescue the UV defect by inducing the
      formation of dorsal tissues. The rescued embryos develop somitic muscle and
      neural tube; however, they lack notochord and anterior head structures.

PMID- 8306881
TI  - Developmental regulation of integrin expression at the time of implantation in
      the mouse embryo.
AB  - The trophectoderm layer of the mouse blastocyst differentiates at the late
      blastocyst stage to form the invasive trophoblast that mediates implantation of
      the embryo into the uterine wall. The first sign that trophoblast cells have
      developed an invasion-specific cell behavior appears about 10-15 hours after the
      embryo hatches from the zona pellucida, when the quiescent, non-adherent
      trophectoderm cells initiate protrusive activity and become adhesive to
      extracellular matrix. Our previous findings that trophoblast outgrowth on
      extracellular-matrix-coated substrata involves the integrin family of adhesion
      receptors (Sutherland, A. E., Calarco, P. G. and Damsky, C. H., 1988, J. Cell
      Biol. 106, 1331-1348), suggested that the onset of trophoblast adhesive and
      migratory behavior at the time of implantation may be due to changes in
      expression or distribution of integrin receptors. We have thus examined the mRNA
      and protein expression of individual integrin subunits during pre- and
      periimplantation development (E0-E7.5). A basic repertoire of integrins,
      including receptors for fibronectin (alpha 5 beta 1), laminin (alpha 6B beta 1)
      and vitronectin (alpha v beta 3), was expressed continuously throughout this
      period, whereas the expression of five other integrin subunits was
      developmentally regulated. The mRNA for three of these (alpha 2, alpha 6A and
      alpha 7) was first detected in the late blastocyst, coincident with endoderm
      differentiation and development of attachment competence. The mRNA for another
      (alpha 1) was not detected until after trophoblast outgrowth had begun,
      suggesting that its expression may be induced by contact with matrix. At E7.5,
      three of the temporally regulated integrins (alpha 1, apha 6A, alpha 7), all of
      which can form receptors for laminin, were detected only in the ectoplacental
      cone (differentiating trophoblast), and may thus play specific roles in
      trophoblast adhesion and/or differentiation. Because laminin expression is
      upregulated in decidualized uterine stroma in response to the implanting embryo,
      we examined trophoblast-laminin interactions, using laminin fragments and
      integrin antibodies to determine which integrin receptors were involved.
      Trophoblast cells attached and spread on both the E8 and P1' fragments of
      laminin; however, the P1' binding site was cryptic in intact laminin. Interaction
      with P1' was RGD- and alpha v beta 3-dependent, whereas outgrowth on E8 was RGD
      independent and not inhibited by antibodies to the laminin receptor alpha 6 beta
      1, suggesting that alpha 7 beta 1 is the major trophoblast integrin E8
      receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8306882
TI  - pipsqueak, an early acting member of the posterior group of genes, affects vasa
      level and germ cell-somatic cell interaction in the developing egg chamber.
AB  - We have identified a new member of the posterior group of genes, which we call
      pipsqueak. We show that pipsqueak acts after the establishment of the oskar
      posterior anchor but before the localization of vasa protein during oogenesis.
      Characterization of multiple alleles at the pipsqueak locus shows that pipsqueak,
      like vasa, is required for early stages of oogenesis, including but not limited
      to formation of the egg chamber and progression through Stage 6 of oogenesis.
      Genetic interaction studies suggest that pipsqueak acts at least partially
      through vasa; molecular studies indicate that pipsqueak affects vasa level in the
      ovary. We compare vasa and pipsqueak mutant phenotypes in order to determine
      whether pipsqueak acts solely through vasa, and present a model for the role of
      pipsqueak in posterior pattern formation.

PMID- 8306883
TI  - Structure of the zebrafish snail1 gene and its expression in wild-type, spadetail
      and no tail mutant embryos.
AB  - Mesoderm formation is critical for the establishment of the animal body plan and
      in Drosophila requires the snail gene. This report concerns the cloning and
      expression pattern of the structurally similar gene snail1 from zebrafish. In
      situ hybridization shows that the quantity of snail1 RNA increases at the margin
      of the blastoderm in cells that involute during gastrulation. As gastrulation
      begins, snail1 RNA disappears from the dorsal axial mesoderm and becomes
      restricted to the paraxial mesoderm and the tail bud. snail1 RNA increases in
      cells that define the posterior border of each somite and then disappears when
      somitic cells differentiate. Later in development, expression appears in cephalic
      neural crest derivatives. Many snail1-expressing cells were missing from mutant
      spadetail embryos and the quantity of snail1 RNA was greatly reduced in mutant no
      tail embryos. The work presented here suggests that snail1 is involved in
      morphogenetic events during gastrulation, somitogenesis and development of the
      cephalic neural crest, and that no tail may act as a positive regulator of
      snail1.

PMID- 8306884
TI  - Expression of a lacZ transgene reveals floor plate cell morphology and
      macromolecular transfer to commissural axons.
AB  - The floor plate is situated at the ventral midline of the neural tube and is an
      important intermediate target for commissural axons. During elongation, these
      axons converge bilaterally on the ventral midline neural tube and after crossing
      the floor plate make an abrupt rostral turn. Ample evidence indicates that the
      initial projection of commissural axons to the floor plate is guided by a
      chemotropic factor secreted by floor plate cells. However, the way in which the
      subsequent interaction of these axons with the floor plate leads them to make
      further trajectory changes remains undefined. In an effort to gain further
      understanding of the structure and function of floor plate cells, we have taken
      advantage of a line of transgenic mice in which these cells express beta
      galactosidase and thus can be stained by histochemical means. In this line, a
      genomic imprinting mechanism restricts the expression of the lacZ transgene to
      only a proportion of the floor plate cells, allowing their morphology to be
      appreciated with particular clarity. Our analysis revealed that the basal
      processes of floor plate cells are flattened in their rostrocaudal dimension and
      possess fine lateral branches which are aligned with commissural axons.
      Unexpectedly, beta-galactosidase activity was also detected within longer
      transverse linear profiles traversing the floor plate whose ultrastructural
      appearance was not that of floor plate cells but instead corresponded to that of
      commissural axons. Enzyme activity was not detected in more proximal axonal
      segments or in the neuronal cell bodies from which these axons originated.
      Therefore, we propose that the transgene product, and potentially other proteins
      synthesized by floor plate cells, can be transferred to decussating axons.

PMID- 8306885
TI  - Normal development of mice carrying a null mutation in the gene encoding the L14
      S-type lectin.
AB  - The L14 lectin is a 14 x 10(3) M(r) carbohydrate binding protein belonging to the
      family of S-type lectins. The pattern of expression of this protein during mouse
      embryogenesis suggests that it may have multiple roles during pre- and post
      implantation development. Using the technique of homologous recombination in
      embryonic stem cells, we have introduced a null mutation in the gene encoding the
      L14 lectin and generated a strain of mice carrying the mutant allele. We report
      here that homozygous mutant animals that lack the L14 lectin develop normally and
      are viable and fertile. The absence of any major phenotypic abnormalities in
      these mutant animals suggests that other protein(s) potentially compensate for
      the absence of the L14 lectin. Here we show that a related protein termed L30, a
      lectin that has carbohydrate binding specificity similar to that of L14, is
      present in the same embryonic cell populations as L14 at the time of
      implantation, suggesting that the two S-type lectins may be capable of functional
      substitution at this early stage of embryogenesis.

PMID- 8306886
TI  - IMP-L2: an essential secreted immunoglobulin family member implicated in neural
      and ectodermal development in Drosophila.
AB  - The Drosophila IMP-L2 gene was identified as a 20-hydroxyecdysone-induced gene
      encoding a membrane-bound polysomal transcript. IMP-L2 is an apparent secreted
      member of the immunoglobulin superfamily. We have used deficiencies that remove
      the IMP-L2 gene to demonstrate that IMP-L2 is essential in Drosophila. The
      viability of IMP-L2 null zygotes is influenced by maternal IMP-L2. IMP-L2 null
      progeny from IMP-L2+ mothers exhibit a semilethal phenotype. IMP-L2 null progeny
      from IMP-L2 null mothers are 100% lethal. An IMP-L2 transgene completely
      suppresses the zygotic lethal phenotype and partially suppresses the lethality of
      IMP-L2 null progeny from IMP-L2 null mothers. In embryos, IMP-L2 mRNA is first
      expressed at the cellular blastoderm stage and continues to be expressed through
      subsequent development. IMP-L2 mRNA is detected in several sites including the
      ventral neuroectoderm, the tracheal pits, the pharynx and esophagus, and specific
      neuronal cell bodies. Staining of whole-mount embryos with anti-IMP-L2 antibodies
      shows that IMP-L2 protein is localized to specific neuronal structures late in
      embryogenesis. Expression of IMP-L2 protein in neuronal cells suggests a role in
      the normal development of the nervous system but no severe morphological
      abnormalities have been detected in IMP-L2 null embryos.

PMID- 8306887
TI  - Programmed cell death in the Drosophila CNS is ecdysone-regulated and coupled
      with a specific ecdysone receptor isoform.
AB  - At adult emergence, the ventral CNS of Drosophila shows a group of approximately
      300 neurons, which are unique in that they express 10-fold higher levels of the A
      isoform of the ecdysone receptor (EcR-A) than do other central neurons. This
      expression pattern is established early in metamorphosis and persists throughout
      the remainder of the pupal stage. Although these cells represent a heterogeneous
      group of neurons, they all share the same fate of undergoing rapid degeneration
      after the adult emerges from the pupal case. One prerequisite for this death is
      the decline of ecdysteroids at the end of metamorphosis. Treatment of flies with
      20-hydroxyecdysone blocks the death of the cells, but only if given at least 3
      hours before the normal time of degeneration. The correlation of a unique pattern
      of receptor isoform expression with a particular steroid-regulated fate suggests
      that variations in the pattern of receptor isoform expression may serve as
      important switches during development.

PMID- 8306888
TI  - In vitro manipulation of early mouse embryos induces HIV1-LTRlacZ transgene
      expression.
AB  - We report here that the transcriptional activity of early mouse embryos is
      affected by their manipulation and culture in vitro, using transgenic embryos
      that express the reporter gene lacZ. We examined the pattern of expression of the
      lacZ gene fused to the human immunodeficiency virus type 1 long terminal repeat
      during the preimplantation stages. Transgene expression is induced as early as
      the two-cell stage in embryos developed in vitro, while there is no constitutive
      expression at the same stage in embryos developed in vivo. We have established a
      relation between this inducible expression occurring in vitro and an oxidative
      stress phenomenon. Indeed, when the culture medium is supplemented with
      antioxidants such N-acetyl-cysteine or CuZn-superoxide dismutase the transgene
      expression is markedly reduced. We also present evidence that the transgene
      expression in vitro coincides with the onset of the embryonic genome activation
      as attested by the synthesis of the 70 x 10(3) M(r) protein complex. Therefore,
      this transgene expression could prove to be a useful tool in our understanding of
      the molecular mechanisms involved in this crucial developmental event.

PMID- 8306889
TI  - The formation and maintenance of the definitive endoderm lineage in the mouse:
      involvement of HNF3/forkhead proteins.
AB  - Little is known about genes that govern the development of the definitive
      endoderm in mammals; this germ layer gives rise to the intestinal epithelium and
      various other cell types, such as hepatocytes, derived from the gut. The
      discovery that the rat hepatocyte transcription factor HNF3 is similar to the
      Drosophila forkhead gene, which plays a critical role in gut development in the
      fly, led us to isolate genes containing the HNF3/forkhead (HFH) domain that are
      expressed in mouse endoderm development. We recovered mouse HNF3 beta from an
      embryo cDNA library and found that the gene is first expressed in the anterior
      portion of the primitive streak at the onset of gastrulation, in a region where
      definitive endoderm first arises. Its expression persists in axial structures
      derived from the mouse equivalent of Hensen's node, namely definitive endoderm
      and notochord, and in the ventral region of the developing neural tube.
      Expression of the highly related gene, HNF3 alpha, appears to initiate later than
      HNF3 beta and is first seen in midline endoderm cells. Expression subsequently
      appears in notochord, ventral neural tube, and gut endoderm in patterns similar
      to HNF3 beta. Microscale DNA binding assays show that HNF3 proteins are
      detectable in the midgut at 9.5 days p.c. At later stages HNF3 mRNAs and protein
      are expressed strongly in endoderm-derived tissues such as the liver. HNF3 is
      also the only known hepatocyte-enriched transcription factor present in a highly
      de-differentiated liver cell line that retains the capacity to redifferentiate to
      the hepatic phenotype. Taken together, these studies suggest that HNF3 alpha and
      HNF3 beta are involved in both the initiation and maintenance of the endodermal
      lineage. We also discovered a novel HFH-containing gene, HFH-E5.1, that is
      expressed transiently in posterior ectoderm and mesoderm at the primitive streak
      stage, and later predominantly in the neural tube. HFH-E5.1 is highly similar in
      structure and expression profile to the Drosophila HFH gene FD4, suggesting that
      HFH family members have different, evolutionarily conserved roles in development.

PMID- 8306890
TI  - Taurine promotes the differentiation of a vertebrate retinal cell type in vitro.
AB  - The retina offers a model system for investigating the mechanisms that control
      cell type determination and differentiation in the vertebrate central nervous
      system. Previously, rod photoreceptor development in vitro was found to require a
      diffusible activity released by retinal cells (D. Altshuler and C. Cepko,
      Development 114, 947-957, 1992). In this report, we show that retinal-cell
      conditioned medium and extracts contain two separable activities that influence
      rod development: a > 10 kDa inhibitory activity, and a stimulatory activity that
      is < 1 kDa and heat stable. Taurine was found to be a component of the < 1 kDa
      fraction and to stimulate rod development when added to retinal cultures. Taurine
      was not the only rod-promoting factor in these retinal preparations, however, as
      conditioned medium and extracts stimulated a higher level of rod development than
      did taurine alone. Taurine uptake into cells could be blocked without inhibiting
      taurine's ability to stimulate rod development, arguing against an osmoregulatory
      or nutritive mechanism of action. Finally, a competitive antagonist of taurine's
      bioactivity was identified and shown partially to inhibit rod development in
      retinal explants, suggesting that taurine may normally act to stimulate rod
      development in the retina. These results provide evidence for three activities,
      one of which is taurine, that are candidate regulators of rod photoreceptor
      development in vivo.

PMID- 8306891
TI  - Nuclear localization of the protein encoded by the Wilms' tumor gene WT1 in
      embryonic and adult tissues.
AB  - The human Wilms' tumor gene WT1 encodes a putative transcription factor
      implicated in tumorigenesis and in specifying normal urogenital development. We
      have studied the distribution of WT1 protein and mRNA using immunohistochemistry
      and in situ hybridization. Monoclonal antibodies were raised against a peptide
      specific to the first alternative splice site of WT1. Two antibodies specifically
      reacted on Western blot to this WT1 isoform. Immunofluorescence localized WT1
      protein to podocytes during mesonephric and metanephric development. In situ
      hybridization revealed a similar pattern of expression except that WT1 mRNA was
      also present in metanephric blastema and renal vesicles. Messenger RNA expression
      was most pronounced in the kidneys during early fetal development and declined
      thereafter. In contrast, WT1 protein was readily detectable in glomerular
      podocytes throughout adulthood. WT1 protein in Wilms' tumor was present in
      blastema and glomeruloid structures. Expression in the female gonad was linked to
      the different stages of granulosa cell development. In the male gonad, expression
      was restricted to Sertoli cells and their precursors, the embryonic tunica
      albuginea and the rete testis. The intracellular distribution of the WT1 protein
      was investigated by confocal laser microscopy and was demonstrated to be
      exclusively nuclear. The nuclear distribution and the selective pattern of
      expression support the proposed role of WT1 as a transcription factor active
      during urogenital development. The persistence of WT1 expression in the adult
      kidney suggests a role in homeostasis of the podocyte.

PMID- 8306892
TI  - The role of noradrenaline in the differentiation of amphibian embryonic neurons.
AB  - The possibility that monoamines might act as signalling molecules during the
      early development of the nervous system has been examined in embryos of the
      amphibian Xenopus laevis. The distributions of 5-hydroxytryptamine, dopamine,
      noradrenaline and their precursor, dopa, were determined from the fertilized egg
      up to the late neurula stages using High Performance Liquid Chromatography,
      formaldehyde-induced fluorescence and antibody staining. 5-hydroxytryptamine was
      not detected until the tail bud stage. The fertilized egg contained significant
      concentrations of dopa (10(-6) M) and dopamine (10(-7) M). Both monoamines
      persisted with little change in concentration up to the late neurula stage. Early
      neurula stage embryos contained very low levels of noradrenaline. Aldehyde
      induced fluorescence showed that monoamines are localized in dorsal regions of
      the embryo, in ectoderm and mesoderm cells. Monoamines were not present in
      endoderm cells. Immunocytochemical staining showed dopamine predominantly in the
      ectoderm, except in future neural regions where it was found also in the
      mesoderm. Dopamine staining was always most intense in dorsal regions of the
      embryo. The consequences for subsequent neuronal differentiation of interfering
      with the biosynthesis and receptor binding of monoamines during neurulation was
      assayed. Neuronal differentiation was monitored quantitatively in cultures set up
      as the neural tube closed and qualitatively in intact tadpoles that were left to
      develop for two days after washout of test reagent. The number of neurons, the
      number of muscle cells and the total number of differentiated cells were counted
      after 18-24 hours of culture. Comparison of the number of neurons that
      differentiated from control and treated embryos showed that inhibition of
      dopamine beta-hydroxylase, the enzyme catalysing the conversion of dopamine to
      noradrenaline, during the neural plate stages reduced substantially subsequent
      neuronal differentiation. The differentiation of myocytes and the total number of
      differentiated cells were not affected. Exogenous noradrenaline (10(-6) M) or
      dopamine (10(-6) M) could increase the number of neurons that differentiated
      subsequently in culture. Interfering with noradrenaline binding to receptors with
      receptor antagonists during neurulation showed that alpha-adrenergic receptor
      antagonists reduced substantially the subsequent differentiation of neurons. The
      differentiation of myocytes and the total number of differentiated cells were not
      affected. The effect of alpha-adrenergic receptor antagonists was overcome by the
      simultaneous inclusion of noradrenaline or alpha-receptor agonists, but not
      agonists at beta-adrenergic receptors. The quantitative reduction in the
      differentiation of neurons was paralleled by defects in the Central Nervous
      System of intact tadpoles.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8306893
TI  - Autosomal P[ovoD1] dominant female-sterile insertions in Drosophila and their use
      in generating germ-line chimeras.
AB  - The 'dominant female-sterile' technique used to generate germ-line mosaics in
      Drosophila is a powerful tool to determine the tissue specificity (germ line
      versus somatic) of recessive female-sterile mutations as well as to analyze the
      maternal effect of recessive zygotic lethal mutations. This technique requires
      the availability of germ-line-dependent, dominant female-sterile (DFS) mutations
      that block egg laying but do not affect viability. To date only one X-linked
      mutation, ovoD1 has been isolated that completely fulfills these criteria. Thus
      the 'DFS technique' has been largely limited to the X-chromosome. To extend this
      technique to the autosomes, we have cloned the ovoD1 mutation into a P-element
      vector and recovered fully expressed P[ovoD1] insertions on each autosomal arm.
      We describe the generation of these P[ovoD1] strains as well as demonstrate their
      use in generating germ-line chimeras. Specifically, we show that the Gap1 gene,
      which encodes a Drosophila homologue of mammalian GTPase-activating protein, is
      required in somatic follicle cells for embryonic dorsoventral polarity
      determination.

PMID- 8306894
TI  - Drosophila segmentation: after the first three hours.

PMID- 8306895
TI  - Differential expression of neurotrophin receptors during renal development.
AB  - Early kidney differentiation is driven by local cell-cell interactions. The
      metanephrogenic mesenchyme stimulates the epithelial ureter bud to grow and
      branch, whereas the ureter bud stimulates the mesenchyme to convert into a new
      epithelium. These interactions may be dependent on local growth factors and their
      receptors. We studied the expression of receptors for nerve growth factors during
      kidney development. Expression of the low- and high-affinity receptors was cell
      type specific. The low-affinity NGF receptor was found in the uninduced
      mesenchyme at early developmental stages, but in the glomerular podocytes at
      later developmental stages. In contrast, the high-affinity trkB receptor was
      found in the cortical mesenchyme cells that will differentiate into stroma. The
      trkC receptor was found only weakly expressed and in a few parts of the
      collecting ducts. The role of these receptors and c-ros, a receptor-type kinase
      expressed on the tip of the ureter bud, was studied by modified antisense
      oligonucleotides. However, we found that both sense, antisense and nonsense
      phosphorothioate oligonucleotides inhibited mouse and rat embryonic kidney
      development in vitro. The oligonucleotides appeared to be toxic for rodent
      embryonic kidneys in the experimental conditions that we used. Moreover,
      oligonucleotides did not penetrate well into the epithelial sheets in the organ
      cultures. We conclude that studies with phosphorothioate antisense
      oligonucleotides in organ cultures of embryonic kidneys should be interpreted
      with caution. Our current data do not allow us to not assign a function for the
      low- or high-affinity NGF receptors or c-ros in kidney development.

PMID- 8306896
TI  - Bacterial drug resistance, diarrhoeal diseases and laboratory diagnosis of
      pulmonary tuberculosis.

PMID- 8306897
TI  - Acquired tetracycline resistance genes in nosocomial Salmonella typhimurium
      infection in a Kenyan hospital.
AB  - Tetracyclines have been among the most widely used antibiotics worldwide. Plasmid
      mediated tetracycline resistance among hospital strains of bacteria has continued
      to rise and of major concern has been the transfer of resistance to pathogenic
      organisms. Bacteraemia due to hospital acquired S. typhimurium has been a major
      cause of morbidity at Kenyatta National Hospital (KNH), hence the need to study
      drug susceptibility pattern of this organism. This study also characterized the
      tetracycline resistance genes using oligonucleotide probes. Ninety seven S.
      typhimurium strains isolated from patients at KNH were used. Agar dilution method
      was used to determine minimum inhibitory concentration (MIC). Plasmids were
      isolated from each strain and the different plasmid profiles were grouped by
      their molecular weights into 6 patterns. Out of 97, 87 (88%) strains were
      resistant. MIC ranged from 1 microgram/ml to 128 micrograms/ml. Genes encoding
      for tetracycline resistance were located on plasmids of molecular weights 65 MDa,
      5.2 or both. Plasmid-encoded antimicrobial resistance is likely to spread to
      other pathogenic organisms, reduce our ability to treat the infection and
      increase the cost and duration of treatment.

PMID- 8306898
TI  - Antimicrobial resistance patterns and plasmid survey of Salmonella and Shigella
      isolated in Ibadan, Nigeria.
AB  - Antibiotic resistance patterns among Salmonella and Shigella spp isolated from
      diarrhoeic human beings were studied. Eleven antibiotic resistance patterns were
      observed. Plasmid survey of the isolates revealed the presence of multiple
      plasmids in thirty two of the fifty three strains. More plasmid patterns than
      antibiotic resistance were observed. Incidence of Salmonellosis and Shigellosis
      in this environment is caused by genetically unrelated Salmonella and Shigella
      strains although with identical drug resistance patterns.

PMID- 8306899
TI  - A comparative study on the reliability of the fluorescence microscopy and Ziehl
      Neelsen method in the diagnosis of pulmonary tuberculosis.
AB  - Pulmonary tuberculosis (PTB) is the most common presentation of tuberculosis (TB)
      in Kenya. For the diagnosis of PTB the sputum smear is used because it is
      technically simple, non-invasive and cheap. The reliability of direct smear
      examination for the diagnosis of TB has however frequently been questioned. To
      address this problem, a study comparing the reliability of fluorescence
      microscopy (FM) and Ziehl-Neelsen (ZN) staining method for examination of direct
      smear in the diagnosis of PTB was carried out at the Respiratory Disease Research
      Unit Laboratory, Nairobi, Kenya. A total of 1480 sputum specimens collected from
      patients with suspected PTB were analyzed. Two direct smears were prepared from
      each specimen, one stained using FM and the other using the ZN method. Culture
      results were used as the gold standard for assessment. Specificity was 97% and
      96% for FM and ZN methods, respectively. The sensitivity of the FM method was 80%
      and that of the ZN method 65% (p < 0.001). Overall agreement was 86.8%. Positive
      smears which were missed on the ZN stained smears (15%) contained low density
      bacilli on both FM stained smears and on culture. The use of FM greatly improves
      the diagnostic value of the sputum smear especially in patients with a low
      density of bacilli who are likely to be missed on ZN stained smears. The method
      is economical in both time and expense and is recommended for laboratories
      handling large numbers of sputum specimens.

PMID- 8306900
TI  - The microbiology of acute diarrhoeal disease in the eastern province of Saudi
      Arabia.
AB  - A prospective study of acute diarrhoeal diseases in the Eastern Province of Saudi
      Arabia was carried out over a 19-month period to determine aetiology, risk
      factors and other epidemiological characteristics. Of the 853 subjects studied,
      344 were cases and 509 controls. More cases were seen in children than in adults.
      Enteric pathogens were detected in 49% of the cases, but none in the controls. Of
      the pathogens, 68% were bacterial with Salmonella (34%) and Shigella species
      (14.7%) being the most common; Campylobacter jejuni emerged as an important cause
      especially in adults. Contrary to most reports, rotaviruses were responsible for
      only 11.5% of the cases in children. Entamoeba histolytica (13.5%) and Giardia
      intestinalis (10.4%) were parasites commonly detected. Shigella organisms were
      the only pathogens that were isolated in hospital cases without being isolated in
      cases from the community.

PMID- 8306901
TI  - Cardiovascular features in adolescents and adults with sickle cell anaemia.
AB  - Fifty five sickle cell anaemia (SCA) patients at the Kenyatta National Hospital
      were studied with a view to elucidating their cardiovascular status. Their age
      range was 13 to 27 years (median 18.9 years). They comprised 27 males and 28
      females and their mean haemoglobin concentration was 8.5 +/- 1.4 g/dl.
      Haemoglobin level of 8.0-9.9 g/dl seen in 30 patients was noted to confer the
      lowest incidence of exertional dyspnoea and palpitation. Similarly, patients with
      this haemoglobin level had the lowest mean heart rate. The mean blood pressure
      was 114.9 +/- 9.9 mmHg systolic and 64.6 +/- 10 mmHg diastolic. Blood pressures,
      ejection fraction (EF) and differential fibre shortening (%D) were found to be
      directly related to haemoglobin level, whereas cardio-thoracic index (CTI) and
      left ventricular dimensions were inversely related to haemoglobin level. Mean
      echocardiographic measurements were within normal limits and left ventricular
      functions were found to be normal in 80.9% of the patients indicating that the
      majority of SCA patients at the Kenyatta National Hospital have good cardiac
      function.

PMID- 8306902
TI  - Comparative study of the efficacy and tolerability of hydroflumethiazide versus
      propranolol in Africans with mild to moderate hypertension.
AB  - Sixty patients with Diastolic Blood Pressure (DBP) of 100-110mmHg matched for
      age, sex and Bp levels were randomly assigned to propranolol 80mg daily or
      Hydroflumethiazide (HFM) 50mg daily. HFM causes a significant reduction in
      systolic blood pressure (SBP) and DBP within 4 weeks compared both with baseline
      and propranolol (SBP 143.7 +/- 12.3 vs 158.1 +/- 10.9mmHg, P < 0.05; DBP 92.0 +/-
      4.5 vs 102.4 +/- 5.1mmHg, P < 0.05), (SBP 143.7 +/- 12.2 vs 152 +/- 11.0mmHg P <
      0.05; DBP 92.0 +/- 4.5 vs 101.1 +/- 6.1mmHg, P < 0.05), respectively. Propranolol
      produced no significant difference from the baseline at 4 weeks (SBP 152.0 +/-
      H.0 vs 154.1 +/- 11.5mmHg NS; DBP 101.1 +/- 6.1 vs 102.2 +/- 5.6mmHg, NS).
      Reduction in BP by HFM was maintained after 8 and 12 weeks with further reduction
      but which did not achieve statistical significance. Increased dose of propranolol
      (160mg daily) after 4 weeks caused significant reduction in BP by 8 week (SBP
      146.8 +/- 11.8 vs 152.0 +/- 11.0mmHg, P < 0.05; DBP 95.9 +/- 4.4 vs 101.1 +/-
      6.1mmHg P < 0.05), which was maintained upto 12 weeks. The values however
      remained higher than in the HFM group. More patients in the HFM group achieved
      target BP (< 140/90), SBP 53.8% vs 29.6% P < 0.05, DBP 69.2% vs 14.8% P < 0.01.
      Incidence of side effects was similar and will be discussed. Thiazides are
      superior to B'blockers as initial monotherapy in black hypertensives.

PMID- 8306903
TI  - Quantitative assessment of oestrogen and progesterone receptors on fine-needle
      aspirates and cryostat sections of breast carcinomas: how does this compare with
      biochemical assays?
AB  - In this study monoclonal antibodies to oestrogen receptors in the ER-ICA kit
      (Abbott) and to progesterone receptors (Biogenex) were used to determine the
      presence of those receptors in fine needle aspirates and cryostat sections. The
      degree of positivity is semi-quantitated and the results compared to biochemical
      assays (Dextran-Coated Charcoal Method) performed on the same specimens. Out of
      14 cases that were positive on the biochemical assay, 11 (77%) were positive on
      ER-ICA performed on the FNA material, and there was a 100% agreement on the
      cryostat sections (11/11). PR-ICA on the cytospin smears and cryostat sections
      agreed in 63% and 90% respectively.

PMID- 8306904
TI  - Hypertension in Sierra Leone stroke population.
AB  - A retrospective study of 87 hospitalized Sierra Leonean stroke patients is
      presented. The mean age was 50.9 years with a male to female ratio of 2:1.
      Hypertension was present in 68% of patients but only in those above 30 years of
      age. It was also more prevalent in females than males. Mean arterial pressure
      increased with age up to 40 years after which is remained constant. Thirteen
      patients died during admission. Fatal cases were significantly older (p < 0.001),
      and had a higher mean arterial pressure (p < 0.05) than survivors. It is
      considered that hypertension is a greater risk factor in stroke in the West
      Africans than in other African regional groups. The historical relationship
      between the West African and black American, who also have a high prevalence of
      hypertension, is recognized and discussed. More research on hypertension and
      stroke in populations such as these may reveal important clues to the aetiology
      and pathogenesis of these serious vascular disorders.

PMID- 8306905
TI  - Fluoride and abrasive content in commonly used dentifrices on the Kenyan market.
AB  - About one decade ago, a heated debate on the appropriateness of fluoride
      dentifrices in Kenya culminated in the introduction of no-fluoride brands.
      Analysis of dentifrices that were available on the market in 1989/1990 confirmed
      two distinctly different categories, the fluoride and the low or no-fluoride
      types. Among the former, the mean ionic fluoride concentration ranged between 0.4
      and 1.36 mg/g while the total fluoride concentration ranged between 1.15 and
      114.68 mg/g. The low or no-fluoride dentifrices had less than 0.03 mg/g ionic
      fluoride and less than 2.14 mg/g total fluoride. The mean abrasive (powder)
      content ranged between 26.5 g% and 78.5 g%. The gel categories had markedly lower
      powder values than the pastes. The ash values of the powders ranged between 15.8
      g% and 85 g% and did not have an obvious relationship with the powder content.
      Despite the obvious risk of increasing exposure to excessive fluoride among
      children, presently, the situation has reverted to the pre-debate time. Given the
      ubiquitous nature of ingestable fluoride in the region, provision of guidelines
      and guidance on the sale of dentifrices by the government and consumer
      organisations, and increased accountability of the manufacturers are recommended.

PMID- 8306906
TI  - The management of depressed skull fractures in children at Muhimbili Medical
      Centre, Dar es Salaam, Tanzania.
AB  - Thirty eight consecutive children with depressed fracture of the skull admitted
      to the Paediatric Surgical Unit (PSU) of Muhimbili Medical Centre (MMC), Dar es
      Salaam between January 1986 to May 1992 were studied. There were 22 boys and 16
      girls. Age range was from birth to 10 years. A fall of one form or another
      accounted for 25 (65.00%) patients. Falling from a sister's or mother's back
      occurred in 4 (10.5%) patients, while falling from trees was a cause in 8 (21%)
      patients. Objects hitting on the head accounted for 6 (15.8%) patients. The
      objects included stones in 3 and falling coconut fruits in three. Traffic motor
      accidents accounted for 5 (13.2%) patients. In 35 (92.1%) patients, the fractures
      were closed while in 3 (7.9%) they were open. The fractures were located in the
      frontal or parietal bone in 27 (76.3%) patients. The 3 coconut fractures were
      located at the sagittal area. Only 4 (10.5%) patients had focal neurological
      signs. Convulsions were recorded in 3 patients while loss of consciousness was
      observed in 4 patients. Surgery was performed on 22 (57.9%) patients while
      conservative approach was practised in 16 (42.1%). The indications for surgery
      were cosmetics in 15 patients, compound fracture in 3 patients, focal
      neurological deficit in 2 patients, and torn dura presenting with Pseudo
      meningocele in 2 patients.

PMID- 8306907
TI  - Factors associated with epileptiform EEG patterns in Nigerian epileptics.
AB  - We reviewed electroencephalographic (EEG) records of 626 epileptic patients for
      the frequency of epileptiform patterns (EP). The purpose of this study was to
      determine the factors determining the occurrence of EP. Epileptiform pattern was
      detected in 46% of patients studied. The occurrence of EP was associated with
      age, seizure type, longer duration of epilepsy, and proximity of EEG examination
      to last attack. We found no association between seizure frequency, medication
      status at EEG examination and the occurrence of EP. The yield of diagnostically
      useful findings in the interictal EEG would be increased if the test is performed
      as close as possible to the last seizure.

PMID- 8306908
TI  - Radiation dose as a factor in the choice of routine pre-operative dental
      radiographs.
AB  - Radiation doses received by patients during dental x-ray examinations were
      measured in 95 patients referred to the X-ray Department of the Teaching Dental
      Hospital, University of Nairobi. The mean skin dose for single periapical films
      was 5.96 milligray (596 millirads) with the bitewing view recording a mean dose
      of 5.57 milligray (mGy). During a 14-film full-mouth periapical survey, mean
      doses ranged from 10.3-16.2 mGy for the upper jaw and 10.1-13.5 mGy for the lower
      jaw, respectively, depending on the region of dentition. In these full-mouth
      examinations, the distribution of skin dose over different parts of the dentition
      showed a characteristic pattern which may be explained by the overlap of
      radiation fields in the aggregated series of exposure. Orthopantomography
      recorded lower mean skin doses of 3.26 mGy in the molar region and 2.67 mGy at
      the posterior midline at the level of the 2nd cervical vertebra. The relative
      merits of intra-oral radiography versus orthopantomography are discussed, with
      radiation dosage as one of the factors to be considered. Some observations are
      made on measures to reduce patient dose.

PMID- 8306909
TI  - Rising incidence of cerebral malaria in Lagos, Nigeria: a postmoterm study.
AB  - One hundred and forty seven cases of acute malaria were diagnosed at autopsy
      between 1988 and 1991 at the Lagos University Teaching Hospital (LUTH). In 67
      (46.5%) cases death was attributed to cerebral malaria (CM). There was a gradual
      increase in the incidence of CM during the period under review. Both sexes were
      affected equally but more children than adults succumbed. The highest death rate
      was recorded in the age group 1-5 years with a peak in the 2nd and 3rd year.
      There were seven adults out of which one was intenerant white lady. Only one of
      the six adult Nigerians had travelled outside Africa and stayed away for about
      four years. The commonest presenting symptoms were: fever only, fever with
      convulsions and/or coma and fever with gastrointestinal symptoms such as vomiting
      and diarrhoea. The majority of the adults were comatose (five out of seven)
      without fever on admission. A review of the English literature on the diagnosis,
      pathogenesis and management of CM is also presented. The possible reasons of the
      rising incidence of CM in a holoendemic region such as Nigeria are discussed.

PMID- 8306910
TI  - Surgery of the oesophagus: a Nairobi experience.
AB  - On average, for every 100 patients with malignant dysphagia admitted into the
      Kenyatta National Hospital (KNH) in Nairobi, 28 will have their tumour resected.
      Seven in the tumour resected group will die during the postoperative period while
      there will be 12 deaths occurring in patients before surgery.

PMID- 8306911
TI  - Premenstrual tension among nurses in Nairobi, Kenya.
AB  - A sample of 400 nurses at the Kenyatta National Hospital in Nairobi were
      interviewed by means of investigator-administered questionnaire to determine the
      prevalence and some other aspects of premenstrual tension (PMT) amongst them.
      Premenstrual tension (PMT) syndrome was found in 95.5% of the study group, with
      mastalgia being the commonest symptom (79.0%) followed by abdominal bloating
      (75.0%). Some features such as suicidal tendencies, inability to cope, insomnia
      were found to be rare among them. There was no correlation between age, marital
      status, parity, or dysmenorrhoea and premenstrual tension. Almost all the nurses
      with PMT, did not consider it an illness, rather as normal part of their
      femininity. As a result only 6.5% of them had changed their activities during
      this period, and only 3.1% had used medication for it. It is concluded that
      premenstrual tension is prevalent among women in Kenya, and that because of their
      attitude towards it, the condition does not appear to be associated with any
      serious morbidity.

PMID- 8306912
TI  - The effect of cassava leave intake on thyroid hormone and urinary iodine.
AB  - The effect of consuming large amounts of cassava leaves on thyroid function and
      urinary iodine was studied. Twenty volunteers were given 200 gm of boiled cassava
      leaves twice a day for 12 consecutive days. Thyroid hormones triiodothyronine and
      thyroxine were significantly lower by 9 days. Urinary iodine excretion was also
      significantly decreased. Cassava leaves, consumed in large amounts by aborigines,
      probably caused goitres by decreasing iodine absorption.

PMID- 8306913
TI  - Laryngectomy and coloplasty for major oesophagogastric corrosive stricture: case
      report and literature review.
AB  - A 25-year old male with a major corrosive stricture of the larynx, oesophagus and
      stomach had left isoperistaltic colon interpostion with good results. The colon
      was passed transpleuraly to emerge in the neck lateral to the sternomastoid.

PMID- 8306914
TI  - Refractoriness of domestic cats to infection with a Kenyan strain of Leishmania
      donovani.

PMID- 8306915
TI  - Oh! To be a hospital doctor.

PMID- 8306916
TI  - Impulse patterns of single encoding sites of human secondary muscle spindle
      afferents.
AB  - 1. By recording single-fibre action potentials (APs) from human sacral nerve
      roots, the impulse patterns of 6 secondary spindle afferents could be identified,
      analysed and compared with the impulse trains of oscillatory firing alpha 2
      motoneurons. 2. Secondary spindle afferents fired with single APs, doublets,
      bursts and equidistant APs. On the assumption that the most simple firing pattern
      of a single fibre with a shortest interspike interval (II) of 80 msec was
      generated by a single encoding site, the firing patterns of the other afferents
      could be splitted into firing patterns of single encoding sites with similar II
      distributions and also with a shortest II of about 80 msec. 3. Successive IIs
      also reflected the different ways of firing of the secondary muscle spindle
      afferents. A fibre from a paraplegic with bladder dyssynergia seemed to show a
      higher activity than a comparable probably normal fibre. The doublet IIs of two
      secondary spindle afferents ranged from about 9 to 14 msec with peaks at 10.2,
      11.2 and 13 msec in the distributions. Multiple encoder sites increased discharge
      rates of parent fibres, but did not always regularize the output discharge. 4.
      The simultaneously plotted impulse patterns of 4 secondary spindle afferents
      showed coordinated firing: they did not fire simultaneously but regularized the
      summed activity. A phase of 50 msec (range 30 to 70 msec) often occurred between
      the spindle afferent APs and the impulse trains of an oscillatory firing alpha 2
      motoneuron. An afferent drive of the oscillator with a certain phase is likely.

PMID- 8306917
TI  - Phase correlated adequate afferent action potentials as a drive of human spinal
      oscillators.
AB  - 1. By recording, with 2 pairs of wire electrodes, single-fibre action potentials
      (APs) from lower sacral nerve roots of a brain-dead human and a patient with
      spinal cord lesion, impulse patterns of afferent APs and impulse trains of
      oscillatory firing motoneurons could be identified and correlated. 2. Two highly
      activated secondary muscle spindle afferents increased and decreased their
      activity at about 0.3 Hz. The duration of the doublet interspike interval of a
      secondary spindle afferent fibre showed no correlation to the oscillation period
      of the motoneuron. 3. A continuously oscillatory firing motoneuron innervating
      the external and sphincter showed more transient breaks with the reduction of the
      number of phase correlated APs from 2 spindle afferents, indicating a looser
      oscillation. A transient brake of a 157 msec period alpha 2-oscillation could be
      correlated to the shift of a interspike interval distribution peak from 150 to
      180 msec of the adequate afferent input, which suggests a transient loss of the
      necessary phase relation. 4. Oscillatory firing alpha 2-motoneurons innervating
      the external bladder and anal sphincters fired independently according to their
      phase correlated APs from the urinary bladder stretch receptor and muscle spindle
      afferents respectively; the bladder motoneuron slightly inhibited the anal
      motoneuron. 5. Receptors of the afferents and innervation sites of oscillatory
      firing motoneurons could be located within the urinary tract and the anal canal.

PMID- 8306918
TI  - Action potential patterns of intrafusal gamma and parasympathetic motoneurons,
      secondary muscle spindle afferents and an oscillatory firing alpha 2-motoneuron,
      and the phase relations among them in humans.
AB  - 1. Single-fibre action potentials (APs) were recorded from a S4 root of a brain
      dead human and a patient with a spinal cord lesion, with 2 pairs of wire
      electrodes, and distribution histograms of conduction velocity frequencies were
      constructed. By plotting the intrafusal velocity main gamma peak on a logarithmic
      scale, the peak splitted into one dynamic ad two static gamma-peaks and an
      additional peak of parasympathetic fibres. 2. Apart from the doublet firing, a
      single gamma 1 (dynamic) and a single gamma 21-motoneuron (static) fired with
      shortest interspike intervals of 80 msec, similarly as a simultaneously firing
      secondary spindle afferent fibre; with 13 msec the doublet interspike interval of
      the gamma 1-motoneuron was very similar to that of the spindle afferent fibre.
      The intrafusal motoneurons fired with patterns very similar to those of secondary
      spindle afferents, and they did not fire in the oscillatory mode for high
      activations as alpha 2 and alpha 3-motoneurons do. 3. The stability of the
      oscillatory firing of a sphincteric alpha 2-motoneuron increased with the
      increasing phases of approx. 50 msec between the APs of the gamma-motoneurons and
      the impulse train of the motoneuron following bladder catheter pulling. Moreover,
      in a certain phase range the number of phases between the APs of a gamma 1
      motoneuron and a secondary spindle afferent fibre increased upon stimulation and,
      as shown earlier, also the number of phase correlations between the APs of some
      secondary spindle afferents and the impulse train of the oscillatory firing alpha
      2-motoneuron increased. Phase relations between the APs of two spindle afferents
      also increased upon the bladder catheter pulling. During the oscillatory firing
      of the alpha 2-motoneuron a phase loop seemed to exist from the APs of the alpha
      2-motoneuron to the APs of certain gamma-motoneurons, to the APs of certain
      secondary spindle afferent fibres and back to the APs of the alpha 2-motoneuron,
      in similarity to the phase recoupling of electronic oscillators. 4. Single gamma
      motoneurons changed their activity levels rhythmically, similarly as the
      secondary spindle afferents, often with a frequency of 0.3 Hz. Parasympathetic
      intrafusal motoneurons fired at a constant activity level for about 10 sec, and
      activated up to 6 single encoding sites of a parent secondary spindle afferent
      fibre. Shortly after the recruitment of a new encoding site, the interspike
      intervals of the parent fibre were similar again.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8306919
TI  - Electrophysiological studies in preterm and growth retarded low birth weight
      babies.
AB  - Twenty-six fullterm intrauterine growth retarded (FT-IUGR) and 17 preterm
      appropriate for gestational age (PT-AGA) babies constituted study subjects.
      Offsprings were subjected to anthropometry (weight, crown-heel length and head
      circumference) and motor nerve conduction velocity (MNCV) as well as H-reflex
      latency (H-RL) at right median nerve. The PT-AGA babies had significantly lower
      MNCV and higher H-RL compared to FT-IUGR babies. When intrauterine growth
      retardation was severe (weight group 1500-1800 g) the means for MNCV and H-RL
      between FT-IUGR babies and PT-AGA babies of comparable weight were similar. FT
      IUGR babies weighing between 1800-2100 g had significantly higher MNCV and lower
      H-RL compared to FT-IUGR babies weighing < 1800 g. The FT-IUGR babies where all
      the three anthropometric parameters were retarded (symmetrical intrauterine
      growth retardation) had significantly lower MNCV and higher H-RL compared to FT
      IUGR babies where weight alone or in combination with crown-heel length was
      retarded.

PMID- 8306920
TI  - [Biological markers in schizophrenia].
AB  - Based on a review of the literature, the article deals with the major biological
      markers of schizophrenia. Recent developments in molecular biology have shown a
      possible association between schizophrenia and various HLA markers (A1, A2, A9,
      A10, A28, B27, BW16), and a linkage--in several families--between the disease and
      some polymorphisms of chromosome 5. On the other hand, chromosome X might also be
      involved. Neuropathological abnormalities have often been found in the brains of
      schizophrenics, such as cellular alterations in the basal ganglia and the limbic
      structures. Investigations by means of CT-scan and Magnetic Resonance Imaging
      have pointed out an enlargement of cerebral ventricles and/or an atrophy of
      frontal areas, especially amongst patients with prominent negative symptoms. The
      dopaminergic hypothesis of schizophrenia reposes on the major following facts:
      the therapeutic efficiency of neuroleptics (dopaminergic antagonists); a positive
      correlation between plasma homovanillic acid (metabolite of dopamine)
      concentration and the severity of schizophrenic illness; a higher density of
      dopaminergic D2-receptors (revealed by Positron Emission Tomography thanks to
      specific radioligands), particularly in the striatum; and an abnormal plasmatic
      growth-hormone response to apomorphine (dopaminergic agonist). Central
      noradrenergic dysfunctions might also occur in paranoid schizophrenia, as
      underlined by higher cerebrospinal fluid levels of norepinephrine, and a lack of
      decrease of plasma 3-methoxy-4-hydroxy-phenylglycol (MHPG, metabolite of
      norepinephrine) after clonidine (alpha-2-adrenergic agonist) dispensation.
      Nevertheless, in patients with predominating negative symptoms, this is a trouble
      in serotoninergic functions which has been suggested. In the field of immunology,
      some findings such as alteration in lymphocytes populations (T4/T8, CD5), anti
      cerebral auto-antibodies, abnormal lymphocytes responses to mitogens, decreased
      production of interleukin-2, have lead to two main hypotheses: autoimmunity and
      immunologic incompetence. On the other hand, electrophysiological studies have
      shown a hypovariability of alpha-rythm on the EEG; a lower amplitude of the
      component P300 from visual evoked potentials; sleep disorders such as a shorter
      rapid eye movement sleep latency and a decreased total slow-wave sleep percent;
      irregular smooth pursuit eyes-movements; an electrodermal response according to
      either the hyper-responder either the non-responder type. At last, troubles in
      sensory integration, motor coordination and attention have also been
      demonstrated. All those many findings outline the heterogeneity of schizophrenic
      disorders.

PMID- 8306921
TI  - [Schizophrenia and language disorders].
AB  - The speech of schizophrenics is idiosyncratic, possibly unrelated to thought
      disorders. Review of relevant literature indicates that schizophrenic speech
      disorders include: errors in the use of pronouns, articles, verbs and verb
      tenses, which are neither pointed out or corrected; absence of redundancy,
      skewering of the meaning of words, faulty establishment of common references with
      others. Sentences appear disjointed due to improvised vocabulary and the scant
      use of conjunctions and other linking words or phrases. Speech is slow, trite,
      and fails to convey information proportionate to speech production. Discourse is
      self-centered and the needs of others are ignored. In general, schizophrenic
      speech performance worsens the more ambiguous, intimate or complex the topic.

PMID- 8306922
TI  - [Dementia in diffuse cortical Lewy body disease].
AB  - Diffuse Lewy body disease has not been yet described in France, although some
      authors, essentially Japanese ones reported cases of this disease. A man began at
      age 56 to be very apathetic with memory disturbances. Later, he developed
      aphasia, stereotypies, and mild parkinsonian rigidity. He died in cachexia, three
      years after the onset of the disease. Post-mortem examination showed diffuse
      senile plaques and tangles in the cortex. But there was also a striking widening
      of Lewy bodies, in the pons and in the frontal, temporal and cingular cortex.
      These Lewy bodies were located in the 5th cortical layer, and their immature and
      irregular shape made them difficult to identify. The authors discuss the role of
      each lesions on the clinical disturbances, in regard to other described cases.

PMID- 8306924
TI  - [Lithium in the treatment of refractory depression].
AB  - The definition of treatment-resistant depression is variously interpreted. There
      is no agreement of different authors on its meaning. The present vagueness of
      criteria for the diagnosis of a refractory depression contrasts with the many
      studies reporting potentiation of antidepressants by lithium. De Montigny in
      1981, after early works by Zall and by Lingjaerde, initiated this approach that
      still remains poorly understood in terms of biochemical mechanisms. A review of
      the controlled studies shows that the delay of antidepressant action varies and
      the term "lithium potentiation" does not seem totally relevant. From a
      pharmacological point of view, several types of data suggest a synergic
      potentiation rather than a true potentiation. This effect applies to all classes
      of antidepressants and improves about 50% of patients who did not respond
      positively to an adequate treatment received during 4 to 6 weeks. Many questions
      remain unanswered particularly concerning the lithium levels, factors predicting
      a positive response and the strategy for the maintenance treatment. Studies are
      necessary in order to compare the relevance of this potentiation technique with
      the mere substitution by another antidepressant and to understand the biochemical
      mechanisms underlying the synergic effect.

PMID- 8306923
TI  - [Comparative double-blind study of bromazepam versus prazepam in non-psychotic
      anxiety].
AB  - The efficacy of bromazepam and prazepam for the different components of anxiety:
      inhibition, asthenia and somatisation is evaluated in a multi-centric,
      comparative and randomised study, conducted as double blind and in parallel
      groups in 159 adult patients showing a manifest anxiety according to the F.D.A.
      criteria. After a 7 day wash-out period, the patients receive either bromazepam
      in a 12 mg/d dose or prazepam in a 40 mg/d dose, over 4 weeks (D0-D28), then in a
      decreasing dose from D28 to D43; follow-up is carried out using the anxious
      inhibition scale W.P.2, auto-questionnaire A.D.A., the Hamilton anxiety scale and
      the Tyrer questionnaire (benzodiazepine withdrawal symptoms questionnaire).
      Patients are evaluated seven times during the study: at day 7 for inclusion, day
      0 for randomisation, then day 7 and day 14 for following visits, at day 28 for
      efficacy and tolerance evaluation, and at day 50 for utilisation and withdrawal
      evaluation. The major efficacy criteria are the evolution of inhibition, asthenia
      and somatisation as compounds of anxiety respectively evaluated by W.P.2 scale,
      asthenic partial score of autoquestionnaire A.D.A. and somatic partial score of
      Hamilton anxiety scale. The analysis of results don't show any significant
      difference between the two groups on the evolution of the components asthenia and
      inhibition. However the evolution of the somatic component clearly makes a
      significant difference in favour of bromazepam. There is also a significant
      difference in terms of global anxiolytic action efficacy, in favour of
      bromazepam.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8306925
TI  - [Comparative efficacy of bromocriptine, carbamazepine and cyproheptadine with
      neuroleptics in 24 refractory chronic schizophrenic patients].
AB  - Different drugs have been used as adjuvant to neuroleptics in chronic
      schizophrenia. Bromocriptine, carbamazepine and cyproheptadine have shown an
      efficacy added to neuroleptics in schizophrenia. In our study, 24 chronic
      schizophrenic inpatients considered to be resistant to neuroleptics were treated
      double blind with the associations haloperidol (40 mg a day)--carbamazepine (400
      mg a day), haloperidol (40 mg a day)--bromocriptine (2.5 mg a day), haloperidol
      (40 mg a day)--cyproheptadine (24 mg a day) and haloperidol (40 mg a day)-
      placebo. The drugs were given successively, in a randomized succession using a
      latin square procedure, for four 5-weeks periods. A psychiatric assessment using
      the Brief Psychiatric Rating Scale (BPRS), the SANS (Scale for Assessment of
      Negative Symptoms) and the SAPS (Scale for Assessment of Positive Symptoms)
      occurred every two weeks. Extrapyramidal symptomatology and abnormal movements
      were assessed using the AIMS (Abnormal Involuntary Movement Scale) and the
      Simpson-Angus scale. Using an ANOVA, we cannot show any clinical efficacy of any
      of those three drugs as an adjuvant to haloperidol. The discrepancy between our
      results and the data of the literature can be linked to the high specificity of
      our sample (resistance to neuroleptics). We cannot show any specific efficacy of
      those drugs on positive and negative symptoms, using the sub-factors of the SAPS
      and SANS.

PMID- 8306926
TI  - [Electroconvulsive therapy in the treatment of Parkinson disease].
AB  - This review of the literature shows that Parkinson's disease can be considered as
      an indication of sismotherapy. The therapeutic effects of ECT on the extra
      pyramidal syndrome are reviewed whether it is associated with a depression or
      not. The various biological mechanisms of the antiparkinsonian effect of ECT are
      discussed ie the increase of the permeability of the brain blood barrier, the
      action on the dopamin metabolism and the dopamin receptors and the action on the
      opioid receptors and melatonin. The role of maintenance ECT in the treatment of
      Parkinson's disease is cleared up. In conclusion, it appears that sismotherapy
      can be considered as an adjuvant therapy in Parkinson's disease especially when
      there is a resistance to dopatherapy.

PMID- 8306927
TI  - Prehospital considerations in the pregnant patient.
AB  - The prehospital care of the pregnant patient is aimed at expeditious transport of
      the patient to an appropriate facility combined with rapid intervention to
      stabilize the mother, including oxygen administration and fluid resuscitation.
      Optimal care of the fetus is dependent on appropriate management of the mother.

PMID- 8306928
TI  - Medical illness during pregnancy.
AB  - Several medical illnesses commonly occur in the pregnant patient admitted to the
      emergency department. Some, such as hyperemesis gravidarum and urinary tract
      infection, occur exclusively or with increased frequency in pregnancy.
      Thromboembolic disease is the leading cause of maternal death in pregnancies that
      survive the first 3 months. Sickle cell disease, seizures, diabetes, and asthma
      are common in young women, and the emergency physician needs to know the ways in
      which pregnancy alters presentation and management of these illnesses.

PMID- 8306929
TI  - Drug therapy during pregnancy and lactation.
AB  - This article reviews the altered physiology of pregnancy and its impact on drug
      pharmacokinetics together with the pharmacokinetics of drug transport across the
      placenta and into the breast milk. Also reviewed are the potential adverse
      effects of maternal drug therapy on the fetus and neonate and the difficulties in
      assessing the potential risks of therapy. Finally, these principles are applied
      in the discussion of a number of specific drugs frequently prescribed in the
      emergency department setting.

PMID- 8306930
TI  - Acute abdominal pain in pregnancy.
AB  - Some degree of abdominal pain is virtually physiologic in pregnancy, for which
      reason these women will commonly present to the emergency physician for clinical
      evaluation. Appendicitis is the commonest nonobstetric surgical malady
      complicating pregnancy; however, its clinical presentation may resemble several
      other surgical as well as medical entities reviewed in this article. The clinical
      evaluation of these patients is generally confounded because the symptoms typical
      of these illnesses are common to pregnancy itself, and the physical examination
      of the abdomen is hampered by the pregnant state. Nevertheless, prompt clinical
      diagnosis and surgical intervention when indicated is necessary to minimize
      maternal and especially fetal mortality. The general reluctance to use
      conventional radiographic study of these patients must be dismissed whenever the
      physician is confronted with severely ill or unstable patients. Whenever
      diagnosis is uncertain, liberal use of surgical and obstetric consultants is
      warranted.

PMID- 8306931
TI  - Trauma during pregnancy.
AB  - The appearance of a pregnant trauma patient is rare even in the busiest of trauma
      centers. Management of these cases can present difficult challenges. A successful
      outcome for both mother and child is dependent on an immediate team approach and
      response involving physician, nursing, and ancillary staff. The disciplines of
      emergency medicine, trauma surgery, obstetrics, and perinatology must be involved
      primarily in a timely and appropriate fashion. Other consultants required for the
      optimal treatment of injuries and pregnancy must also play a timely role. An
      aggressive rather than timid approach to resuscitation, diagnosis, and treatment
      of these patients must be taken. Knowledge of the normal physiologic changes
      occurring during pregnancy, special attention to prevention and early recognition
      of occult maternal hypoxia and hypovolemia, as well as a high index of suspicion
      for injuries to mother and fetus likely to occur during pregnancy should guide
      and temper management strategies. Care providers should resist emotional
      distractions and the urge to focus on the fetus before the mother is properly
      stabilized and evaluated. They should be cognizant of the fact that an apparently
      stable mother may be compensating at the expense of the fetus. Finally, the tenet
      of what benefits the mother will ultimately benefit the fetus should be adhered
      to. When these points are kept in mind, the potential for successful outcome and
      satisfying results is greatest for all parties involved.

PMID- 8306932
TI  - Emergency complications of labor and delivery.
AB  - The care of the pregnant patient presenting to the emergency department with
      labor or delivery complications requires an understanding of signs and symptoms
      of disease for the maternal and fetal patient. This article reviews management of
      common labor and delivery complications that may occur in the emergency
      department. The management of premature labor, premature rupture of the
      membranes, emergency delivery procedure, resolution of shoulder dystocia,
      prolapsed umbilical cord, and perimortem cesarean section are discussed.

PMID- 8306933
TI  - Postpartum emergencies.
AB  - Included among the challenges that the emergency physician may encounter is care
      of the postpartum patient. A number of disorders such as postpartum hemorrhage,
      endometritis, and eclampsia are unique to the puerperal patient, although other
      disorders, such as cardiomyopathy and pulmonary embolus, may be seen with an
      increased frequency in patients after delivery. A knowledge of the presenting
      features, required diagnostic studies, and recommended treatments will allow
      prompt and effective management.

PMID- 8306934
TI  - Neonatal resuscitation.
AB  - All emergency departments should be adequately equipped and well prepared to
      handle a newborn delivery and resuscitation. It is important to remember that
      most neonates will respond to drying, warming, positioning, suctioning, and
      tactile stimulation and that overzealous and invasive resuscitation is not only
      unwarranted in most cases, but substantially increases the risk of iatrogenic
      complications. After the initial management, further therapy is based on
      assessment of respirations, heart rate, and skin and mucous membrane color. An
      algorithm outlining neonatal resuscitation is presented in Figure 6.

PMID- 8306935
TI  - Drug therapy for obstetric emergencies.
AB  - Drug therapy for the treatment of obstetric emergencies frequently consists of
      medications not commonly used by the emergency physician such as Rho(D) immune
      globulin, 15-methyl prostaglandin F2a (carboprost), and ritodrine hydrochloride.
      This article focuses on those agents for which emergency use is confined to the
      obstetric emergency or where the administration of a commonly used drug acquires
      unique characteristics because of the clinical situation. In either case, a
      thorough understanding of the indications, contraindications, dose, route of
      administration, and side effects of these drugs will allow prompt and effective
      management of a variety of obstetric emergencies.

PMID- 8306936
TI  - Vaginal bleeding during pregnancy.
AB  - The treatment of vaginal bleeding during pregnancy may require little more than
      careful evaluation of the patient. Sometimes, however, the emergency physician
      must perform the highest resuscitative skills. In either case, the fears and
      concerns of the mother for herself and the fetus are considerable. This article
      describes, in four broad categories, how to diagnose and treat bleeding in
      pregnancy.

PMID- 8306937
TI  - Ectopic pregnancy.
AB  - The incidence of ectopic pregnancies has increased dramatically over the past 20
      years, resulting in significant maternal morbidity and mortality. This article
      reviews the epidemiology, pathogenesis, clinical manifestations, diagnostic
      testing, differential diagnosis, treatment, prognosis, and medico-legal
      considerations in the evaluation of the patient with a suspected or confirmed
      pregnancy.

PMID- 8306938
TI  - Hypertensive disorders of pregnancy.
AB  - Overall, the goal of the emergency physician is proper recognition of the gravid
      woman whose pregnancy is complicated by hypertensive disease, particularly
      preeclampsia-eclampsia. As the classic triad of hypertension, proteinuria, and
      edema does not always occur simultaneously, supporting signs and symptoms as well
      as laboratory data may be necessary to support the diagnosis. Once the diagnosis
      is established, drug therapy aimed at the prevention of seizures and emergent
      control of blood pressure should be instituted to stop progression of the
      disease. Although many agents are undergoing investigation, magnesium sulfate and
      hydralazine remain the drugs of choice for anticonvulsant and antihypertensive
      therapy, respectively. Early consultation with an obstetrician should facilitate
      timely termination of the pregnancy with the least possible trauma to the mother
      and infant.

PMID- 8306939
TI  - Diagnostic modalities in the pregnant patient.
AB  - Pregnancy determination may be made within 3 to 4 weeks' gestational age using
      radioimmunoassay or two-site ELISA assay. Using serum progesterone
      concentrations, serial quantitative beta-hCG levels, culdocentesis, sonography,
      laparoscopy, and fetal heart rate determination, the clinician is able to
      determine fetal viability and implantation site often within 6 to 7 weeks'
      gestational age. Improved sensitivity in diagnostic modalities, as well as
      increased awareness of the often subtle clinical findings in ectopic pregnancy
      are probably both responsible for the decline in morbidity and mortality seen
      with ectopic pregnancy over the past 25 years. As the incidence has seen an even
      greater increase than this decline, however, ectopic pregnancy remains the
      leading cause of first-trimester maternal mortality in this country. With the use
      of imaging in pregnancy, the question of fetal safety must also arise. The
      modalities currently used in the first trimester of pregnancy appear to pose
      minimal risks to the developing fetus if used only when necessary, and then with
      caution.

PMID- 8306940
TI  - Sexually transmitted and genital tract infections during pregnancy.
AB  - Sexually transmitted diseases comprise one of the most common medical
      complications of pregnancy. Prompt treatment is essential to minimize the risk of
      fetal and neonatal adverse consequences. At this time, however, no pharmacologic
      therapy is routinely employed for the viral STDs during pregnancy, including HIV,
      HSV, and hepatitis B virus. Appropriate antibiotic treatment, considered in the
      context of fetal drug effects, provides high cure rates for many of the other
      sexually transmitted agents. The approach of the emergency physician to STDs
      centers on recognition and treatment; however, all physicians encountering this
      patient population have a responsibility to facilitate access to primary
      prophylaxis for STD. This means ensuring that issues related to education
      regarding transmission of STDs, safer sex, and sexual contact counseling are
      addressed initially or via a primary care referral. In the appropriate setting,
      complications of pregnancy due to STDs should also be addressed.

PMID- 8306941
TI  - On the model controversy for substrate-induced spin-state transition in
      cytochrome P450: (a new perspective).
AB  - Three models have been proposed for substrate-induced spin-state transition in
      cytochrome P450. These are referred to as two-, three- and four-state models. In
      this communication the three models are reviewed with respect to their
      experimental basis and their ability to accommodate the results reported on the
      effects of substrates on spin-state and reduction of various P450's. In addition,
      a new perspective is presented.

PMID- 8306942
TI  - Epidermal growth factor modulates cholera toxin induced mammary gland
      development.
AB  - Ovariectomized mice were either sham operated or sialoadenectomized and injected
      daily for 18 days with saline, estradiol + progesterone, cholera toxin or
      estradiol + progesterone+cholera toxin. Mammary development score and DNA were
      increased by estradiol + progesterone, but not by cholera toxin alone. In
      combination with estradiol + progesterone, cholera toxin increased mammary
      development score and mammary DNA. Sialoadenectomy reduced the ability of
      estradiol, progesterone and cholera toxin to induce mammary development. In other
      experiments, mice were primed with estradiol + progesterone for 10 days, and
      mammary tissue removed for in vitro culture with various combinations of insulin,
      aldosterone, cholera toxin and epidermal growth factor. In combination with
      insulin and aldosterone, cholera toxin increased mammary development in vitro.
      Sialoadenectomy reduced the ability of cholera toxin to induce mammary
      development in vitro. The effect of sialoadenectomy on mammary development was
      alleviated by adding epidermal growth factor to culture medium. Biochemical
      studies indicated that sialoadenectomy reduced the ability of estrogen and
      progesterone to induce cyclic AMP dependent protein kinase levels in mammary
      tissue, and also the ability of cholera toxin to induce accumulation of cyclic
      AMP in tissues. These effects of sialoadenectomy were reversed by addition of EGF
      to culture media.

PMID- 8306943
TI  - The effect of digitonin and altered thyroid status on palmitic acid oxidation by
      isolated rat liver mitochondria.
AB  - The effect of altered thyroid status and food-deprivation on palmitic acid
      oxidation in isolated rat liver mitochondria was studied in the absence and
      presence of digitonin. Mitochondria prepared from triiodothyronine-treated
      (hyperthyroid) and food-deprived rats metabolized palmitic acid at the same rate
      as the untreated controls (euthyroid). Mitochondria prepared from
      thyroidectomized (hypothyroid) rats metabolized palmitic acid at a rate lower
      than was that seen with mitochondria from euthyroid controls in either the fed or
      fasted state. Fasting had no effect on palmitic acid oxidation by mitochondria
      prepared from euthyroid rats but diminished the rates seen in both hyper- and
      hypothyroid states. Digitonin (0.04 mg/mg mitochondrial protein) increased the
      sensitivity of the rate of fatty acid oxidation to inhibition by alpha
      bromopalmitic acid. The addition of digitonin to the incubation mixture resulted
      in two-fold increases in the rate of palmitic acid oxidation in all states. This
      study shows that the limitations imposed by hypothyroidism on fatty acid
      oxidation in intact liver are preserved in isolated mitochondria.

PMID- 8306944
TI  - Failure of ethanol to induce changes in gonadotropin gene expression in
      selectively bred ethanol-sensitive rats.
AB  - The recent availability of genetically altered rat lines differing in sensitivity
      to ethanol (EtOH) has allowed deeper investigation into the mechanisms of EtOH
      induced cellular toxicity in several systems. Since the male central reproductive
      axis has been demonstrated to be exquisitely sensitive to EtOH, studies were
      undertaken to determine if the gonadotropin suppression reported earlier could be
      duplicated in one of these selected rat lines. Castrated high alcohol sensitivity
      (HAS), low alcohol sensitivity (LAS) and control alcohol sensitivity (CAS) rats
      were given EtOH or saline acutely. Castrated non-selectively bred Sprague Dawley
      rats were treated similarly and used as an additional control. At sacrifice,
      serum and pituitary luteinizing hormone (LH) and follicle stimulating hormone
      (FSH) levels were obtained and the mRNA levels for both gonadotropins assessed.
      In the selectivity bred animal there was essentially no change in serum or
      pituitary LH or FSH levels between EtOH and saline treated animals. The mRNA
      levels for both LH and FSH similarly were unaffected by EtOH, in striking
      contrast to the non-selectively bred Sprague Dawley rats where serum LH, FSH and
      beta-LH mRNA levels are markedly suppressed after EtOH exposure. The selectively
      bred lines of rats genetically manipulated for high or low EtOH sensitivity, as
      well as their non-selected controls, appeared to have a hypothalamic-pituitary
      reproductive unit that is resistant to EtOH. This is in contrast to Sprague
      Dawley rats, where suppression of this axis previously has been consistently
      demonstrated.

PMID- 8306945
TI  - Cigarette tar promotes neutrophil-induced DNA damage in cultured lung cells.
AB  - We have investigated the ability of aqueous cigarette tar extracts to promote
      human polymorphonuclear leukocyte (PMNL)- and hydrogen peroxide (H2O2)-induced
      DNA single-strand breaks (DNA-SSB) in cultured human lung cells. Tar extract
      itself did not cause any DNA-SSB formation, whereas PMNL (activated with phorbol
      myristate acetate (PMA)) and H2O2 both caused a small but significant DNA-SSB
      formation on their own. On the other hand, if cells were first treated with tar
      extract and then exposed to PMA-activated PMNL or H2O2, the DNA-SSB formation
      increased considerably. Pretreatment with iron-loaded tar extracts caused a
      greater increase after PMNL exposure than pretreatment with regular tar extracts.
      No DNA-SSB formation was found if catalase was present during the PMNL exposure,
      indicating that H2O2 was important for the PMNL-induced DNA damage. These
      findings suggest that cigarette tar promotes neutrophil-induced DNA damage in
      human lung cells and that this effect can be further potentiated by iron. This
      can be of importance in explaining the carcinogenic effects of cigarette smoking
      and the increased risk of lung cancer among asbestos workers and iron miners who
      smoke.

PMID- 8306946
TI  - Prognostic factors of renal dysfunction induced by environmental cadmium
      pollution.
AB  - To assess the influence of environmental cadmium (Cd) exposure on long-term
      outcome, a follow-up study was conducted from 1981-1982 to March 1991 on 3178
      inhabitants living in the Cd-polluted Kakehashi River basin. The standardized
      mortality ratios of the urinary beta 2-microglobulin (beta 2-MG)-, protein-, and
      amino acid-positive subjects of both sexes and the urinary glucose-positive
      female subjects were higher than those of the subjects with urinary-negative
      findings or the general Japanese population during the observation period. After
      adjusting for age using Cox's proportional hazards model, significant
      associations were found between mortality and urinary indices. In multiple
      comparisons using all of the indices, urinary protein and beta 2-MG in the women
      and urinary protein in the men were the factors most contributing to the
      mortality rates. In the urinary protein-negative female group as well, a
      significant association was found between urinary beta 2-MG and mortality. These
      results suggest that the prognosis of subjects with Cd-induced renal dysfunction
      is unfavorable, with the mortality rate increasing even in the early stage of
      proximal tubular dysfunction. Urinary protein and urinary beta 2-MG are important
      prognostic factors, with the latter, in particular, considered to be useful as an
      early index predictive of premature mortality.

PMID- 8306947
TI  - Environmental tobacco smoke and childhood asthma: comparing exposure metrics
      using probability plots.
AB  - This study demonstrates the use of probability plots for assessing exposure
      disease relationships in case-control studies. We reanalyze data from a study of
      childhood asthma and exposure to environmental tobacco smoke, comparing
      alternative measures of smoking intensity. Previous analyses showed a higher mean
      urinary cotinine-to-creatinine ratio (CCR) in cases as compared with controls and
      a statistically significant odds ratio with exposure defined as 30 ng/mg CCR or
      higher. Using probability plots, we compare alternative exposure metrics and
      exposure cutpoints with respect to their ability to detect a statistically
      significant exposure-disease effect. A strong exposure-disease response is
      evident, overall, and the results are fairly robust to the choice of exposure
      cutpoint.

PMID- 8306948
TI  - Effects of low-level winter air pollution concentrations on respiratory health of
      Dutch children.
AB  - During three consecutive winters acute effects of air pollution on respiratory
      health of more than 1000 children living in four nonindustrial communities in the
      Netherlands have been investigated. Each child performed between 6 and 10
      pulmonary function tests on predetermined days. The occurrence of acute
      respiratory symptoms in the children was registered in a daily diary filled out
      by the parents of the children for periods of 3 months. Exposure to air pollution
      was characterized by the ambient concentration of sulfur dioxide, nitrogen
      dioxide, PM10, fine particle sulfate, fine particle nitrate, and nitrous acid. No
      major winter air pollution episode occurred during these winters. Concentrations
      of acid aerosol were low. A weak negative association between the concentrations
      of nitrogen dioxide, PM10, aerosol sulfate, aerosol nitrate, nitrous acid, and
      pulmonary function was found. Sulfur dioxide concentration was not associated
      with pulmonary function. No association of the concentration of the measured
      pollutants with daily incidence and prevalence of acute respiratory symptoms was
      found.

PMID- 8306949
TI  - Nervous system dysfunction among workers with long-term exposure to manganese.
AB  - Neurological disorders, bearing many similarities to Parkinson's disease, have
      been associated with environmental and occupational exposure to manganese (Mn).
      To document early nervous system dysfunction associated with long-term exposure
      to Mn, a battery of neurofunctional tests was administered to workers employed in
      Mn alloy production. Study participation was 95% (n = 115). A matched pair design
      was used; actively working men, with no history of workplace exposure to
      neurotoxins, were recruited from the region as referents. Matching was done on
      the variables: age (+/- 3 years), educational level (+/- 2 years), smoking
      status, and number of children. Stationary environmental sampling indicated that
      Mn levels varied widely (geometric means: Mn dust, 0.89 mg/m3; respirable Mn,
      0.04 mg/m3). The alloy workers had significantly higher levels of whole blood Mn
      (geometric mean: 1.03 microgram/100 ml vs 0.68 microgram/100 ml); no differences
      were observed for urinary Mn. Univariate analysis (paired t test, Signed Rank and
      McNemar) and multivariate analysis of variance (Hotelling-Lawley statistic)
      revealed that the pairs differed on symptom reporting, emotional state, motor
      functions, cognitive flexibility, and olfactory perception threshold; verbal
      fluency, basic mathematics, reading capability, and attentional capacity were
      similar. These findings are consistent with current knowledge on brain Mn
      activity and suggest that manifestations of early manganism can be observed in
      well designed population studies, using sensitive testing methods.

PMID- 8306950
TI  - Mesothelial cell injury caused by pleural leukocytes from rats treated with
      intratracheal instillation of crocidolite asbestos or Corynebacterium parvum.
AB  - The pleural and peritoneal mesothelium is a major target in asbestos exposure
      where mesothelial cell proliferation, exfoliation, and neoplasia have been
      reported in workers and experimental animals. The objective of this study was to
      determine the role of pleural leukocytes in mesothelial cell damage caused by
      asbestos exposure. We therefore investigated detachment and lysis injury to
      mesothelial cells in vitro induced by leukocytes lavaged from the pleural space
      of rats exposed, by intratracheal instillation, to crocidolite asbestos. Our
      studies revealed that normal pleural leukocytes were composed of macrophages,
      lymphocytes, eosinophils, and mast cells. This population showed a small but
      significant recruitment of mast cells and eosinophils 3 to 14 days after
      instillation of crocidolite asbestos; there were also modestly increased levels
      of macrophages present 30 days after low doses of asbestos. One day after
      intratracheal instillation of 5 mg crocidolite asbestos, the pleural leukocytes
      caused detachment injury to mesothelial cells in vitro. This injury was markedly
      reduced 3 days after asbestos exposure and was undetectable by Day 14. One month
      after instillation of asbestos, despite doses of asbestos from 0.5 to 5 mg,
      pleural leukocytes showed no ability to injure mesothelial cells in vitro. In a
      parallel study, pleural inflammation was induced by intratracheal instillation of
      heat-inactivated Corynebacterium parvum. Transient mesothelial cell-detaching
      injury was again expressed by pleural leukocytes 1 day after C. parvum
      instillation. This was likely related to an increase in the percentage of
      neutrophils present on this day. These results show that a single administration
      of crocidolite asbestos, intratracheally, leads to transient activation of
      pleural leukocytes in terms of the ability of these cells to detach mesothelial
      cells from matrix. This finding implies that mesothelial cell proliferation and
      exfoliation found in individuals exposed to asbestos may result from persistent
      stimulation of pleural leukocytes caused by the continuous presence of asbestos
      in the lung.

PMID- 8306951
TI  - Problems in the analysis of cadmium in autopsied tissues.
AB  - A comparison was made between the concentrations of Cd, Zn, Cu, and Fe in the
      organs at autopsy and after fixation in formalin for anatomicopathological
      examination. The concentrations of all the metals were lower in the formalin
      fixed organs. In particular, the residual rates of Cd in the renal cortex and
      medulla were 2.3 and 6.1% of those for the fresh organs, respectively. The Cd
      concentration in the blood collected at autopsy was several hundred times as high
      as the value measured before death and failed to be an indicator of exposure to
      Cd. This phenomenon is specific to Cd and is not found with other metals. In
      determining Cd in the organs collected at autopsy, it is important to avoid
      contamination with blood, remove water around the organs quickly, and preserve
      the organs in sealed polyethylene bags.

PMID- 8306952
TI  - Evidence for an essential role of the sucrose transporter in phloem loading and
      assimilate partitioning.
AB  - Sucrose is the principal transport form of assimilates in most plants. In many
      species, translocation of assimilates from the mesophyll into the phloem for long
      distance transport is assumed to be carrier mediated. A putative sucrose proton
      cotransporter cDNA has been isolated from potato and shown to be expressed mainly
      in the phloem of mature exporting leaves. To study the in vivo role and function
      of the protein, potato plants were transformed with an antisense construct of the
      sucrose transporter cDNA under control of the CaMV 35S promoter. Upon maturation
      of the leaves, five transformants that expressed reduced levels of sucrose
      transporter mRNA developed local bleaching and curling of leaves. These leaves
      contained > 20-fold higher concentrations of soluble carbohydrates and showed a 5
      fold increase in starch content as compared with wild type plants, as expected
      from a block in export. Transgenic plants with a reduced amount of sucrose
      carrier mRNA show a dramatic reduction in root development and tuber yield.
      Maximal photosynthetic activity was reduced at least in the strongly affected
      transformants. The effects observed in the antisense plants strongly support an
      apoplastic model for phloem loading, in which the sucrose transporter located at
      the phloem plasma membrane represents the primary route for sugar uptake into the
      long distance distribution network.

PMID- 8306953
TI  - The meiosis-specific Xmr gene product is homologous to the lymphocyte Xlr protein
      and is a component of the XY body.
AB  - The Xlr (X-chromosome linked, lymphocyte regulated) multigene family was
      previously found to determine, in the lymphoid cell lineage, the stage-specific
      expression of a nuclear protein with a primary sequence suggestive of a
      transcriptional activator function. We report here the characterization of a
      second functional member of the Xlr gene family that is abundantly transcribed in
      testis in a tissue-specific and developmentally regulated manner. The protein
      product of this newly identified gene, called Xmr (Xlr-related, meiosis
      regulated), is located in the nuclei of spermatocytes, early in the prophase of
      the first meiotic division, and later becomes concentrated in the XY nuclear
      subregion where it is in particular associated with the axes of sex chromosomes.
      The Xmr protein provides a new tool for the investigation of sex chromosome
      behaviour during meiosis in mammals.

PMID- 8306954
TI  - Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the
      PIG-A gene.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH), an acquired clonal blood disorder, is
      caused by the absence of glycosyl phosphatidylinositol (GPI)-anchored surface
      proteins due to a defect in a specific step of GPI-anchor synthesis. The cDNA of
      the X-linked gene, PIG-A, which encodes a protein required for this step has
      recently been isolated. We have carried out a molecular and functional analysis
      of the PIG-A gene in four cell lines deficient in GPI-linked proteins, obtained
      by Epstein-Barr virus (EBV) transformation of affected B-lymphocytes from PNH
      patients. In all four cell lines transfection with PIG-A cDNA restored normal
      expression of GPI-linked proteins. In three of the four cell lines the primary
      lesion is a frameshift mutation. In two of these there is a reduction in the
      amount of full-length mRNA. The fourth cell line contains a missense mutation in
      PIG-A. In each case the mutation was present in the affected granulocytes from
      peripheral blood of the patients, but not in normal sister cell lines from the
      same patient. These data prove that PNH is caused in most patients by a single
      mutation in the PIG-A gene. The nature of the mutation can vary and most likely
      occurs on the active X-chromosome in an early haematopoietic stem cell.

PMID- 8306955
TI  - Distinct sub-populations of the retinoblastoma protein show a distinct pattern of
      phosphorylation.
AB  - Phosphorylation of the retinoblastoma protein (pRB) is assumed to regulate its
      growth-controlling function. Moreover, hypophosphorylated and hyperphosphorylated
      forms of pRB can be distinguished by virtue of the distinct affinities with which
      they bind to the cell nucleus. This property allows the identification of
      individual cell nuclei that contain pRB in one or the other form. We show here
      that after cells emerge from a quiescent (G0) state, conversion of their
      complement of pRB into a hyperphosphorylated form occurs in late G1, preceding
      entry into S phase by several hours. Thus, contrary to earlier reports, pRB
      phosphorylation is not co-ordinated with the G1-S transition and may not directly
      regulate it. A distinct set of phosphopeptides is found exclusively in those
      forms of pRB that show the loose nuclear association characteristic of the
      hyperphosphorylated form of pRB. Another set of phosphopeptides is found with
      both hypophosphorylated and hyperphosphorylated forms. This suggests the
      existence of distinct patterns of phosphorylation that are associated with
      different subsets of pRB molecules. We conclude that substantial phosphorylation
      of pRB exists in G1 even prior to the hyperphosphorylation point. Cyclin
      dependent kinases can cause a liberation of pRB from cell nuclei in vitro.
      Phosphorylation by members of this kinase family is therefore likely to be
      directly involved in the change in nuclear affinity in vivo and the associated
      changes in pRB functioning.

PMID- 8306957
TI  - An iron-sulfur center essential for transcriptional activation by the redox
      sensing SoxR protein.
AB  - The soxRS oxidative stress regulon of Escherichia coli is triggered by superoxide
      (O2.-) generating agents or by nitric oxide through two consecutive steps of gene
      activation. SoxR protein has been proposed as the redox sensing gene activator
      that triggers this cascade of gene expression. We have now characterized two
      forms of SoxR: Fe-SoxR contained non-heme iron (up to 1.6 atoms per monomer); apo
      SoxR was devoid of Fe or other metals. The spectroscopic properties of Fe-SoxR
      indicated that it contains a redox active iron-sulfur (FeS) cluster that is
      oxidized upon extraction from E. coli. Fe-SoxR and apo-SoxR bound the in vivo
      target, the soxS promoter, with equal affinities and protected the same region
      from DNase I in vitro. However, only Fe-SoxR stimulated transcription initiation
      at soxS in vitro > 100-fold, similar to the activation of soxS expression in
      vivo. This stimulation occurred at a step after the binding of RNAP and indicates
      a conformational effect of oxidized Fe-SoxR on the soxS promoter. The variable
      redox state of the SoxR FeS cluster may thus be employed in vivo to modulate the
      transcriptional activity of this protein in response to specific types of
      oxidative stress.

PMID- 8306956
TI  - A flower-specific Myb protein activates transcription of phenylpropanoid
      biosynthetic genes.
AB  - Synthesis of flavonoid pigments in flowers requires the co-ordinated expression
      of genes encoding enzymes in th phenylpropanoid biosynthetic pathway. Some cis
      elements involved in the transcriptional control of these genes have been
      defined. We report binding of petal-specific activities from tobacco and
      Antirrhinum majus (snapdragon) to an element conserved in promoters of
      phenylpropanoid biosynthetic genes and implicated in expression in flowers. These
      binding activities were inhibited by antibodies raised against Myb305, a flower
      specific Myb protein previously cloned from Antirrhinum by sequence homology.
      Myb305 bound to the same element and formed a DNA-protein complex with the same
      mobility as the Antirrhinum petal protein in electrophoretic mobility shift
      experiments. Myb305 activated expression from its binding site in yeast and in
      tobacco protoplasts. In protoplasts, activation also required a G-box-like
      element, suggesting co-operation with other elements and factors. The results
      strongly suggest a role for Myb305-related proteins in the activation of
      phenylpropanoid biosynthetic genes in flowers. This is consistent with the
      genetically demonstrated role of plant Myb proteins in the regulation of genes
      involved in flavonoid synthesis.

PMID- 8306958
TI  - Cooperativity in vivo between the E2 transactivator and the TATA box binding
      protein depends on core promoter structure.
AB  - The E2 transactivator protein of bovine papillomavirus 1 (BPV-1) can strongly
      stimulate complex promoters such as that of the herpes simplex virus thymidine
      kinase gene but does not efficiently activate minimal promoters that only contain
      E2 binding sites and a TATA box. Here we show that overexpression of the human,
      but not yeast, TATA box binding protein (TBP) in transfection experiments
      overcomes this block and enables E2 to activate a minimal TATA box-containing
      promoter. This suggests that recruitment of the TFIID complex to such promoters
      is normally a rate limiting step for transcriptional activation by E2 in vivo. In
      contrast, minimal promoters that contain an initiator element in addition to a
      TATA box are efficiently activated by E2 on its own and this activation is only
      moderately enhanced by TBP overexpression. In such E2-responsive promoters the
      TATA box or initiator can be functionally replaced by SP1 binding sites. Both the
      initiator binding protein, TFII-I, and SP1 have been found to interact physically
      with components of the TFIID complex. Since either TBP overexpression or the
      presence of an initiator or SP1 binding sites can increase activation by E2, it
      seems likely that the principal role of the E2 activation domain is to affect a
      step in the formation of the transcription initiation complex that occurs after
      TFIID has bound to the promoter. Sequential action of transcription factors, such
      as TFII-I, SP1 and E2, may be one type of mechanism underlying the widely
      observed phenomenon of transcriptional synergy.

PMID- 8306959
TI  - Tyrosine phosphorylated p91 binds to a single element in the ISGF2/IRF-1 promoter
      to mediate induction by IFN alpha and IFN gamma, and is likely to autoregulate
      the p91 gene.
AB  - ISGF2 was initially identified, purified and cloned as an interferon-alpha (IFN
      alpha) induced transcription factor that binds to the IFN-stimulated response
      element (ISRE) of IFN alpha/beta-stimulated genes (ISGs). It was reported to be
      transcriptionally regulated by several cytokines including IFN alpha and IFN
      gamma. IFN alpha and IFN gamma inducibility is mediated by a single element: a
      high affinity, nearly palindromic version of the IFN gamma activation site (GAS).
      The ISGF2 GAS is bound specifically by p91, which was previously identified as a
      subunit of the ISG activator ISGF3, and shown to mediate IFN gamma induction of
      the GBP gene via a GAS. Tyrosine phosphorylation and DNA binding activity of p91
      parallel transcription of ISGF2 in response to IFN alpha and/or IFN gamma,
      consistent with induction mediated by only a GAS. Transcription of the genes that
      encode p91 and p113, another subunit of ISGF3, is activated only by IFN alpha.
      This result suggests induction mediated by an ISRE, and implies autoregulation,
      requiring the products of both genes. Specificity of the ISRE is the basis for
      the previous conclusion. In contrast, it appears likely that the ISGF2 GAS, and
      p91 or related factors, also mediate induction of ISGF2 by IL-6 and prolactin.
      Convergence of signalling pathways from at least four cytokines on this single
      site would thus be a key aspect of a general role for ISGF2 in cellular growth
      control.

PMID- 8306960
TI  - Structure and function of the b/HLH/Z domain of USF.
AB  - The basic/helix-loop-helix/leucine zipper (b/HLH/Z) transcription factor upstream
      stimulatory factor (USF) and its isolated DNA binding domain undergo a random
      coil to alpha-helix folding transition on recognizing their cognate DNA. The USF
      b/HLH cocrystal structure resembles the structure of the b/HLH/Z domain of the
      homologous protein Max and reveals (i) that the truncated, b/HLH DNA binding
      domain homodimerizes, forming a parallel, left-handed four-helix bundle, and (ii)
      that the basic region becomes alpha-helical on binding to the major groove of the
      DNA sequence CACGTG. Hydrodynamic measurements show that the b/HLH/Z DNA binding
      domain of USF exists as a bivalent homotetramer. This tetramer forms at the USF
      physiological intranuclear concentration, and depends on the integrity of the
      leucine zipper motif. The ability to bind simultaneously to two independent sites
      suggests a role in DNA looping for the b/HLH/Z and Myc-related families of
      eukaryotic transcription factors.

PMID- 8306961
TI  - The HMG box-containing nucleolar transcription factor UBF interacts with a
      specific subunit of RNA polymerase I.
AB  - The mammalian transcription activator protein UBF contains five tandemly repeated
      HMG homology domains which are required for DNA binding. We have used highly
      purified RNA polymerase I (Pol I) and upstream binding factor (UBF) and
      investigated whether these two proteins interact in solution. We show by a
      variety of different experimental approaches, such as immunoprecipitation,
      glycerol gradient sedimentation, affinity chromatography and protein blotting,
      that UBF physically associates with Pol I. Mutational analysis reveals that the
      HMG boxes play an important role in this specific interaction. UBF binds to mouse
      and yeast Pol I, demonstrating that the interaction of UBF with Pol I has been
      conserved during evolution. Interestingly, in both species one Pol I-specific
      subunit (34.5 kDa in yeast and 62 kDa in mouse) was recognized by UBF. No
      specific interaction was observed with Pol II. Unexpectedly, UBF was found to
      associate also with a unique subunit of yeast Pol III. This apparent specific
      interaction of UBF with the two classes of RNA polymerases may reflect
      functionally important interactions of HMG box-containing transcription factors
      with the transcriptional apparatus.

PMID- 8306962
TI  - Identification of amino acid-base contacts in the Myc-DNA complex by site
      specific bromouracil mediated photocrosslinking.
AB  - Myc binds to a 6 bp 2-fold symmetric DNA site: 5'-C-3A-2C-1G+1T+2G+3-3'. Using
      site-specific 5-bromouracil mediated photocrosslinking, we show that His336 of
      Myc contacts, or is close to, the thymine 5-methyl group at 2-fold symmetry
      related positions -2 and +2 of the DNA site in the Myc-DNA complex. Our results
      strongly suggest that homologous amino acids of Myc and Max make equivalent
      contacts in the respective protein-DNA complexes.

PMID- 8306963
TI  - Crystal structure of prokaryotic ribosomal protein L9: a bi-lobed RNA-binding
      protein.
AB  - The crystal structure of protein L9 from the Bacillus stearothermophilus ribosome
      has been determined at 2.8 A resolution using X-ray diffraction methods. This
      primary RNA-binding protein has a highly elongated and unusual structure
      consisting of two separated domains joined by a long exposed alpha-helix.
      Conserved, positively charged and aromatic amino acids on the surfaces of both
      domains probably represent the sites of specific interactions with 23S rRNA.
      Comparisons with other prokaryotic L9 sequences show that while the length of the
      connecting alpha-helix is invariant, the sequence within the exposed central
      region is not conserved. This suggests that the alpha-helix has an architectural
      role and serves to fix the relative separation and orientation of the N- and C
      terminal domains within the ribosome. The N-terminal domain has structural
      homology to the smaller ribosomal proteins L7/L12 and L30, and the eukaryotic RNA
      recognition motif (RRM).

PMID- 8306964
TI  - In vitro nuclear import of snRNPs: cytosolic factors mediate m3G-cap dependence
      of U1 and U2 snRNP transport.
AB  - We have established an in vitro snRNP nuclear import system using digitonin
      permeabilized somatic cells supplemented with cytosolic extracts. As model
      karyophiles we used digoxygenin labelled U1 snRNPs or fluorescein labelled U2
      snRNPs. In vitro nuclear import of snRNPs is inhibited by anti-pore component
      antibodies, consistent with transport occurring through nuclear pores. This
      import requires ATP, cytosolic factors and a nuclear localization signal (NLS).
      SnRNP nuclear accumulation is saturable and distinct from protein transport.
      Nuclear import of snRNPs, in permeabilized NRK cells supplemented with somatic
      cell cytosol, requires the same NLS structures as those identified in micro
      injected mammalian cells. In contrast to the situation in Xenopus oocytes, the
      m3G-cap is not required for in vitro nuclear import of U1 and U2 snRNPs in
      somatic cells. Instead, assembly of the Sm-core domain is both necessary and
      sufficient to mediate snRNP nuclear targeting. Interestingly, when the in vitro
      system was provided with cytosol from Xenopus oocytes instead of somatic cells,
      U1 and U2 snRNP nuclear import was provided with cytosol from Xenopus oocytes
      instead of somatic cells, U1 and U2 snRNP nuclear import was m3G-cap dependent.
      These results indicate that soluble cytosolic factors mediate the differential
      m3G-cap dependence of U1 and U2 snRNP nuclear import in somatic cells and
      oocytes. We also demonstrate the existence of a soluble cytosolic factor whose
      interaction with the U2 snRNP m3G-cap is both saturable and essential for U2
      snRNP nuclear import in Xenopus oocytes.

PMID- 8306965
TI  - Editing of the mitochondrial small subunit rRNA in Physarum polycephalum.
AB  - Post-transcriptional insertion, substitution or deletion of nucleotides in RNA
      (RNA editing) has been observed in RNAs from a number of organisms but always in
      messenger RNA or transfer RNA. We report here that the 17S rRNA of the
      mitochondrial ribosome of Physarum polycephalum is edited at 40 sites with single
      cytidine insertions. The locations of the editing sites are fairly evenly
      distributed throughout the RNA and do not correspond to any obvious feature of
      the primary sequence or secondary structure. In addition to these cytidine
      editing sites are editing sites in which a nucleotide other than cytidine is
      inserted. At two sites a uridine is inserted and at two sites adenosine residues
      are inserted. This is the first report of mixed nucleotide insertional editing.
      These results imply that the editing mechanism in Physarum may be different from
      those proposed for the kinetoplastid protozoa.

PMID- 8306966
TI  - The length and the secondary structure of the D-stem of human selenocysteine tRNA
      are the major identity determinants for serine phosphorylation.
AB  - Selenocysteine tRNA [tRNA(Ser)Sec] has been shown to be serylated by tRNA(Ser)
      synthetase. The serine moiety of seryl-tRNA(Ser)Sec in vertebrates is further
      phosphorylated by a kinase, in addition to being converted into selenocysteine.
      Using site-directed mutagenesis we have introduced a number of mutations into T7
      RNA polymerase transcripts of human tRNA(Ser)Sec. Our results show that most of
      the unique structural features of tRNA(Ser)(Sec), like the 5'-triphosphate, the 9
      bp long acceptor stem and the anticodon, are not identity elements for
      phosphorylation of human seryl-tRNA(Ser)Sec. However, the length and secondary
      structure of the D-stem (6 bp in contrast with 4 bp in the canonical serine tRNA)
      of human tRNA(Ser)Sec, but not its sequence, are the major identity determinants
      which discriminate this tRNA from common tRNA(Ser) and identify it as the
      substrate for phosphorylation by seryl-tRNA(Ser)Sec kinase. This notion is
      confirmed by the fact that normal seryl-tRNA(Ser), which is not a substrate for
      serine phosphorylation, becomes a substrate if two additional base pairs are
      introduced into its D-stem.

PMID- 8306967
TI  - The second to last amino acid in the nascent peptide as a codon context
      determinant.
AB  - Forty-two different sense codons, coding for all 20 amino acids, were placed at
      the ribosomal E site location, two codons upstream of a UGA or UAG codon. The
      influence of these variable codons on readthrough of the stop codons was measured
      in Escherichia coli. A 30-fold difference in readthrough of the UGA codon was
      observed. Readthrough is not related to any property of the upstream codon, its
      cognate tRNA or the nature of its codon-anticodon interaction. Instead, it is the
      amino acid corresponding to the second upstream codon, in particular the
      acidic/basic property of this amino acid, which seems to be a major determinant.
      This amino acid effect is influenced by the identity of the A site stop codon and
      the efficiency of its decoding tRNA, which suggests a correlation with ribosomal
      pausing. The magnitude of the amino acid effect is in some cases different when
      UGA is decoded by a wildtype form of tRNA(Trp) as compared with a suppressor form
      of the same tRNA. This indicates that the structure of the A site decoding tRNA
      is also a determinant for the amino acid effect.

PMID- 8306968
TI  - The chromatin-associated protein H-NS alters DNA topology in vitro.
AB  - H-NS is one of the two most abundant proteins in the bacterial nucleoid and
      influences the expression of a number of genes. We have studied the interaction
      of H-NS with DNA; purified H-NS was demonstrated to constrain negative DNA
      supercoils in vitro. This provides support for the hypothesis that H-NS
      influences transcription via changes in DNA topology, and is evidence of a
      structural role for H-NS in bacterial chromatin. The effects of H-NS on topology
      were only observed at sub-saturating concentrations of the protein. In addition,
      a preferred binding site on DNA was identified by DNase I footprinting at sub
      saturating H-NS concentrations. This site corresponded to a curved sequence
      element which we previously showed, by in vivo studies, to be a site at which H
      NS influences transcription of the proU operon. When present in saturating
      concentrations, H-NS did not constrain supercoils and bound to DNA in a sequence
      independent fashion, covering all DNA molecules from end to end, suggesting that
      H-NS may form distinct complexes with DNA at different H-NS:DNA ratios. The data
      presented here provide direct support for the hypothesis that H-NS acts at
      specific sites to influence DNA topology and, hence, transcription.

PMID- 8306969
TI  - Assembly of phage phi 29 genome with viral protein p6 into a compact complex.
AB  - The formation of a multimeric nucleoprotein complex by the phage phi 29 dsDNA
      binding protein p6 at the phi 29 DNA replication origins, leads to activation of
      viral DNA replication. In the present study, we have analysed protein p6-DNA
      complexes formed in vitro along the 19.3 kb phi 29 genome by electron microscopy
      and micrococcal nuclease digestion, and estimated binding parameters. Under
      conditions that greatly favour protein-DNA interaction, the saturated phi 29 DNA
      protein p6 complex appears as a rigid, rod-like, homogeneous structure. Complex
      formation was analysed also by a psoralen crosslinking procedure that did not
      disrupt complexes. The whole phi 29 genome appears, under saturating conditions,
      as an irregularly spaced array of complexes approximately 200-300 bp long;
      however, the size of these complexes varies from approximately 2 kb to 130 bp.
      The minimal size of the complexes, confirmed by micrococcal nuclease digestion,
      probably reflects a structural requirement for stability. The values obtained for
      the affinity constant (K(eff) approximately 10(5) M-1) and the cooperativity
      parameter (omega approximately 100) indicate that the complex is highly dynamic.
      These results, together with the high abundance of protein p6 in infected cells,
      lead us to propose that protein p6-DNA complexes could have, at least at some
      stages, during infection, a structural role in the organization of the phi 29
      genome into a nucleoid-type, compact nucleoprotein complex.

PMID- 8306970
TI  - The N-terminal domain of a rab protein is involved in membrane-membrane
      recognition and/or fusion.
AB  - Proteins of the YPT1/SEC4/rab family are well documented to be involved in the
      regulation of membrane transport. We have previously reported that rab5 regulates
      endosome-endosome recognition and/or fusion in vitro. Here, we show that this
      process depends on the rab5 N-terminal domain. Treatment of early endosomal
      membranes at a low trypsin concentration essentially abolished fusion and cleaved
      rab5 to a 1 kDa smaller polypeptide. Two-dimensional gel analysis suggested that
      rab5 is one of the few, if not the only, polypeptides cleaved by trypsin under
      these conditions. Whereas endosome fusion could be stimulated by cytosol prepared
      from cells overexpressing rab5 (and thus containing high amounts of the protein),
      this stimulation was abolished by trypsin-treatment of the cytosol. Trypsin
      treated cytosol prepared from mock-transfected cells, which contains very low
      amounts of rab5, showed no inhibitory activity indicating that rab5 is the target
      of trypsin in these experiments. Purified rab5 prepared after expression in
      Escherichia coli was treated with trypsin, which cleaved the protein at the N
      terminus. A synthetic peptide of rab5 N-terminal domain inhibited endosome fusion
      in our cell-free assay. A version of the same peptide truncated at the N-terminus
      or a peptide of rab3 N-terminal domain were without effects. Altogether, these
      observations suggest that the N-terminal domain of rab5 is involved in the
      process of early endosome recognition and/or fusion, presumably because it
      interacts with another component of the transport machinery.

PMID- 8306971
TI  - VIP21/caveolin, glycosphingolipid clusters and the sorting of
      glycosylphosphatidylinositol-anchored proteins in epithelial cells.
AB  - We studied the role of the association between glycosylphosphatidylinositol (GPI)
      anchored proteins and glycosphingolipid (GSL) clusters in apical targeting using
      gD1-DAF, a GPI-anchored protein that is differentially sorted by three epithelial
      cell lines. Differently from MDCK cells, where both gD1-DAF and glucosylceramide
      (GlcCer) are sorted to the apical membrane, in MDCK Concanavalin A-resistant
      cells (MDCK-ConAr) gD1-DAF was mis-sorted to both surfaces, but GlcCer was still
      targeted to the apical surface. In both MDCK and MDCK-ConAr cells, gD1-DAF became
      associated with TX-100-insoluble GSL clusters during transport to the cell
      surface. In dramatic contrast with MDCK cells, the Fischer rat thyroid (FRT) cell
      line targeted both gD1-DAF and GlcCer basolaterally. The targeting differences
      for GSLs in FRT and MDCK cells cannot be accounted for by a differential ability
      to form clusters because, in spite of major differences in the GSL composition,
      both cell lines assembled GSLs into TX-100-insoluble complexes with identical
      isopycnic densities. Surprisingly, in FRT cells, gD1-DAF did not form clusters
      with GSLs and, therefore, remained completely soluble. This clustering defect in
      FRT cells correlated with the lack of expression of VIP21/caveolin, a protein
      localized to both the plasma membrane caveolae and the trans Golgi network. This
      suggests that VIP21/caveolin may have an important role in recruiting GPI
      anchored proteins into GSL complexes necessary for their apical sorting. However,
      since MDCK-ConAr cells expressed caveolin and clustered GPI-anchored proteins
      normally, yet mis-sorted them, our results also indicate that clustering and
      caveolin are not sufficient for apical targeting, and that additional factors are
      required for the accurate apical sorting of GPI-anchored proteins.

PMID- 8306972
TI  - MSG5, a novel protein phosphatase promotes adaptation to pheromone response in S.
      cerevisiae.
AB  - Pheromone-stimulated yeast cells and haploid gpa1 deletion mutants arrest their
      cell cycle in G1. Overexpression of a novel gene called MSG5 suppresses this
      inhibition of cell division. Loss of MSG5 function leads to a diminished adaptive
      response to pheromone. Genetic analysis indicates that MSG5 acts at a stage where
      the protein kinases STE7 and FUS3 function to transmit the pheromone-induced
      signal. Since loss of MSG5 function causes an increase in FUS3 enzyme activity
      but not STE7 activity, we propose that MSG5 impinges on the pathway at FUS3.
      Sequence analysis suggests that MSG5 encodes a protein tyrosine phosphatase. This
      is supported by the finding that recombinant MSG5 has phosphatase activity in
      vitro and is able to inactivate autophosphorylated FUS3. Thus MSG5 might
      stimulate recovery from pheromone by regulating the phosphorylation state of
      FUS3.

PMID- 8306973
TI  - The Drosophila segment polarity gene patched interacts with decapentaplegic in
      wing development.
AB  - The decapentaplegic (dpp) gene of Drosophila melanogaster encodes a polypeptide
      of the transforming growth factor-beta family of secreted factors. It is required
      for the proper development of both embryonic and adult structures, and may act as
      a morphogen in the embryo. In wing imaginal discs, dpp is expressed and required
      in a stripe of cells near the anterior-posterior compartment boundary. Here we
      show that viable mutations in the segment polarity genes patched (ptc) and costal
      2 (cos2) cause specific alterations in dpp expression within the anterior
      compartment of the wing imaginal disc. The interaction between ptc and dpp is
      particularly interesting; both genes are expressed with similar patterns at the
      anterior-posterior compartment boundary of the disc, and mis-expressed in a
      similar way in segment polarity mutant backgrounds like ptc and cos2. This mis
      expression of dpp could be correlated with some of the features of the adult
      mutant phenotypes. We propose that ptc controls dpp expression in the imaginal
      discs, and that the restricted expression of dpp near the anterior-posterior
      compartment boundary is essential to maintain the wild-type morphology of the
      wing disc.

PMID- 8306974
TI  - Nuclear restoration of cytoplasmic male sterility in sunflower is associated with
      the tissue-specific regulation of a novel mitochondrial gene.
AB  - We have previously shown that cytoplasmic male sterility in sunflower is
      associated with the insertion into the mitochondrial DNA of a novel open reading
      frame (ORF) located 3' to the atpA gene. Here, we show that in mitochondria from
      the sterile line, this novel ORF (ORF522) is cotranscribed with atpA. We have
      identified the product of the ORF522 as being a 15 kDa protein previously
      observed in sterile plant mitochondria by in organello translation. Both Western
      blot analysis and in organello translation assays show reduced levels of the 15
      kDa polypeptide upon restoration of fertility. Interestingly, this reduction is
      tissue specific since it is only observed in the male florets from restored
      hybrid plants. These results suggest that the 15 kDa novel polypeptide is
      probably responsible for the CMS phenotype. Northern blot analysis using RNA from
      both seedlings and male florets shows a flower-specific reduction in the level of
      the ORF522 transcript in the restored hybrid line. The reduction is not due to a
      reduced transcription rate as demonstrated by 'run-on' experiments using
      mitochondria isolated from male florets. This suggests that the product of the
      nuclear restorer gene acts at the post-transcriptional level to destabilize the
      novel mitochondrial transcript in a tissue-specific manner and restore male
      fertility.

PMID- 8306975
TI  - Dual role of the tyrosine activation motif of the Ig-alpha protein during signal
      transduction via the B cell antigen receptor.
AB  - The B cell antigen receptor (BCR) is a multimeric protein complex consisting of
      the ligand binding immunoglobulin molecule and the Ig-alpha/beta heterodimer that
      mediates intracellular signalling by coupling the receptor to protein tyrosine
      kinases (PTKs). Transfection of the Ig-alpha deficient myeloma cell line J558L
      microns with expression vectors coding for mutated Ig-alpha allowed us to test
      the function of the tyrosines in the cytoplasmic region of Ig-alpha in the
      context of the BCR. Furthermore we expressed Ig-alpha mutations as chimeric CD8
      Ig-alpha molecules on K46 B lymphoma cells and tested their signalling capacity
      in terms of PTK activation and release of calcium. We show here that the
      conserved tyrosine residues in the cytoplasmic portion of Ig-alpha have a dual
      role. First, they are required for efficient activation of PTKs during signal
      induction and second, one of them is subject to phosphorylation by activated src
      related PTKs. Phosphorylation on tyrosine in the cytoplasmic portion of Ig-alpha
      is discussed as a possible mechanism to couple the BCR to SH2 domain-carrying
      molecules.

PMID- 8306976
TI  - Inhibition and catalysis of carbonic anhydrase. Recent crystallographic analyses.

PMID- 8306977
TI  - Heat-shock proteins as molecular chaperones.
AB  - Functional proteins within cells are normally present in their native, completely
      folded form. However, vital processes of protein biogenesis such as protein
      synthesis and translocation of proteins into intracellular compartments require
      the protein to exist temporarily in an unfolded or partially folded conformation.
      As a consequence, regions buried when a polypeptide is in its native conformation
      become exposed and interact with other proteins causing protein aggregation which
      is deleterious to the cell. To prevent aggregation as proteins become unfolded,
      heat-shock proteins protect these interactive surfaces by binding to them and
      facilitating the folding of unfolded or nascent polypeptides. In other instances
      the binding of heat-shock proteins to interactive surfaces of completely folded
      proteins is a crucial part of their regulation. As heat shock and other stress
      conditions cause cellular proteins to become partially unfolded, the ability of
      heat-shock proteins to protect cells against the adverse effects of stress
      becomes a logical extension of their normal function as molecular chaperones.

PMID- 8306978
TI  - Polymorphism in the lipase genes of Geotrichum candidum strains.
AB  - The fungus Geotrichum candidum produces extracellular lipases. Purification and
      characterization of different lipase isoforms from various G. candidum strains is
      difficult due to the close physical and biochemical properties of the isoforms.
      Consequently, the characterization of these enzymes and their substrate
      specificities has been difficult. We have determined the lipase genes present in
      four strains of G. candidum (ATCC 34614, NRCC 205002, NRRL Y-552 and NRRL Y-553)
      by molecular cloning and DNA sequencing. Each strain contains two genes similar
      to the previously identified lipase I and lipase II cDNAs. Our data suggest that
      no other related lipase genes are present in these strains. Each lipase-gene
      family shows sequence variation (polymorphism) that is confirmed by Southern-blot
      analysis. This polymorphism and the sequence differences between lipase I and
      lipase II have been localized within the previously determined three-dimensional
      structure of lipase II. Although most of the amino acid substitutions are located
      on the protein surface, some are present in structural features possibly involved
      in determining substrate specificity.

PMID- 8306979
TI  - Molecular characterization of a human tyrosinase-related-protein-2 cDNA. Patterns
      of expression in melanocytic cells.
AB  - Pigmentation in mammals is under complex genetic control. Amongst the genes
      involved in this process, those encoding tyrosinase and the tyrosinase-related
      proteins 1 and 2 have been well characterized and share a number of features.
      Recently, the murine tyrosinase-related-protein-2 gene was shown to encode
      dopachrome-tautomerase activity and was mapped to the slaty locus. Human
      tyrosinase and tyrosinase-related-protein-1 genes have been isolated and
      demonstrate a high degree of similarity with their murine counterparts. However,
      there has been limited data regarding the existence of a human homologue for
      tyrosinase-related-protein-2 and its relationship to the other tyrosinase-related
      proteins. In this study, we report the molecular isolation of a cDNA encoding a
      human homologue of the murine tyrosinase-related-protein-2/dopachrome
      tautomerase. We have characterized its expression in human melanocytic cells and
      have analyzed the relationship between dopachrome tautomerase and tyrosinase
      activities with the level of visible pigmentation in these cells. TYRP2 has been
      mapped to the chromosomal region 13q32, thus extending a region of synteny with
      mouse-chromosome 14.

PMID- 8306980
TI  - Quantitative stoichiometry of the proteins of the stimulatory arm of the adenylyl
      cyclase cascade in neuroblastoma x glioma hybrid, NG108-15 cells.
AB  - To understand the details of regulation of guanine-nucleotide-binding-protein
      linked transmembrane cellular-signalling cascades, it is important to know the
      absolute levels of each polypeptide component and the stoichiometry of their
      interactions. Amounts of the IP prostanoid receptor, the stimulatory G protein of
      the adenylyl cyclase cascade (Gs alpha) and the functional complex of Gs alpha
      with adenylyl cyclase, which acts as the cyclic AMP generator, were measured in
      membranes of neuroblastoma x glioma hybrid, NG108-15, cells. As measured by the
      specific binding of [3H]prostaglandin E1, the IP prostanoid receptor was present
      in some 100,000 copies/cell. Gs alpha assessed by quantitative immunoblotting
      with recombinantly expressed protein, was present in considerably higher levels
      (1,250,000 copies/cell). However, the maximal formation of a complex of Gs alpha
      and adenylyl cyclase represented only some 17,500 copies/cell. The previously
      established 8:1 stoichiometry of concurrent downregulation of Gs alpha and the IP
      prostanoid receptor in these cells [Adie, E. J., Mullaney, I., McKenzie, F. R. &
      Milligan, G. (1992) Biochem. J. 285, 529-536] indicates that full-agonist
      occupation of the receptor should be able to activate some 65% of the expressed
      Gs. Despite the potential 70-fold excess of Gs alpha over the Gs alpha/adenylyl
      cyclase complex, IP prostanoid-receptor-agonist-mediated reduction of Gs alpha
      levels by some 35% resulted in a 25% reduction in the maximal formation of the Gs
      alpha/adenylyl cyclase complex. Such results demonstrate that adenylyl cyclase is
      quantitatively the least highly expressed component of this signalling cascade
      and suggests that much of the cellular Gs alpha may not have access to adenylyl
      cyclase.

PMID- 8306981
TI  - Isolation and structure of novel defensive peptides from frog skin.
AB  - In addition to the highly specific cell-mediated immune system, vertebrates
      possess an efficient host-defense mechanism against invading microorganisms which
      involves the synthesis of highly potent antimicrobial peptides with a large
      spectrum of activity. A 34-residue cationic and amphiphatic peptide, designated
      dermaseptin I, was recently isolated from the skin of the arboreal frog
      Phyllomedusa sauvagii and was shown to exhibit microbicidal activity against
      various pathogenic microorganisms including bacteria, yeast, protozoa and
      filamentous fungi. In this study, we report the isolation and characterization of
      four novel antimicrobial peptides from frog skin through the combined use of an
      anti-dermaseptin enzyme immunoassay and an antifungal bioassay. The 28-34-residue
      antimicrobial peptides are cationic, containing 3-5 lysine residues that
      punctuate an alternating hydrophobic and hydrophilic sequence. Based on their
      primary structure, all four peptides can be fitted to a class L amphipathic alpha
      helix which places all lysine residues on the polar side of the helix. The four
      antimicrobial peptides have high sequence similarity with dermaseptin I (53-94%
      similarity) suggesting that their respective genes are all members of the same
      family. In addition, pairwise sequence alignment of dermaseptin I and
      adenoregulin, a 33-residue cationic peptide recently isolated from frog skin and
      shown to enhance the binding of agonists to the A1 adenosine receptor, reveals
      62% similarity (39% amino acid positional identity). Both peptides share a
      similar but non-identical spectrum of antimicrobial activity, being active
      against bacteria, yeast and filamentous molds. However, no significant hemolytic
      activity was found for these peptides which suggests a selectivity for
      prokaryotic cells. These findings indicate that adenoregulin should be included
      in the dermaseptin family of peptides. In addition, tryptic digestion of purified
      pro-dermaseptin I liberated a 15-amino-acid peptide identified as the authentic C
      terminus of dermaseptin I. These results are in accordance with the predicted
      sequences of pro-dermaseptins obtained through molecular cloning, in which the
      dermaseptin progenitor sequences are located at the extreme C-terminus of the
      precursors.

PMID- 8306982
TI  - Trp279 is involved in the binding of quaternary ammonium at the peripheral site
      of Torpedo marmorata acetylcholinesterase.
AB  - Specific photoaffinity labelling of purified acetylcholinesterase from Torpedo
      marmorata by p-N,N-[3H]dimethylamino benzenediazonium and p-N,N-[3H]dibutylamino
      benzenediazonium derivatives was demonstrated. This occurred at the active site
      of the enzyme for lower concentrations of the probes and at the peripheral
      ammonium binding site for higher concentrations. The affinities and the rate
      constants of alkylation for each probe on both sites have been established.
      Specific labelling at the peripheral site of the enzyme with both probes allowed
      the identification of radio-labelled peptides having the common sequence
      K270PQELIDVEW. The radioactivity was always associated with the residue Trp279
      indicating the preferential ammonium complexation with this aromatic residue.

PMID- 8306983
TI  - Stimulation of phospholipase C-beta 2 by recombinant guanine-nucleotide-binding
      protein beta gamma dimers produced in a baculovirus/insect cell expression
      system. Requirement of gamma-subunit isoprenylation for stimulation of
      phospholipase C.
AB  - Recombinant wild-type beta 1 gamma 1 dimers of signal-transducing guanine
      nucleotide-binding proteins (G proteins) and beta 1 gamma 1 dimers carrying a
      mutation known to block gamma-subunit isoprenylation (beta 1 gamma 1 C71S) were
      expressed in baculovirus-infected insect cells. Both wild-type and mutant beta 1
      gamma 1 dimers were found in soluble fractions of infected cells upon subcellular
      fractionation. Anion exchange chromatographic and metabolic-radiolabeling studies
      revealed that the soluble beta 1 gamma 1 preparation contained approximately
      equal amounts of non-isoprenylated and isoprenylated beta 1 gamma 1 dimers.
      Soluble wild-type and mutant beta 1 gamma 1 dimers and native beta 1 gamma 1
      dimers purified from bovine retina were reconstituted with recombinant
      phospholipase C-beta 2. Only isoprenylated beta 1 gamma 1 dimers were capable of
      stimulating phospholipase C-beta 2. The results show that gamma-subunit
      isoprenylation and/or additional post-translational processing of the protein are
      required for beta gamma subunit stimulation of phospholipase C.

PMID- 8306984
TI  - The role of trehalose synthesis for the acquisition of thermotolerance in yeast.
      I. Genetic evidence that trehalose is a thermoprotectant.
AB  - In the yeast Saccharomyces cerevisiae, accumulation of the non-reducing
      disaccharide trehalose is triggered by various stimuli that activate the heat
      schock response. Several studies have shown a close correlation between trehalose
      levels and tolerance to heat stress, suggesting that trehalose may be a
      protectant which contributes to thermotolerance. In this study, we have examined
      mutants defective in genes coding for key enzymes involved in trehalose
      metabolism with respect to the heat-induced and stationary-phase-induced
      accumulation of trehalose and the acquisition of thermotolerance. Inactivation of
      either TPS1 or TPS2, encoding subunits of the trehalose-6-phosphate
      synthase/phosphatase complex, caused an inability to accumulate trehalose upon a
      mild heat-shock or upon initiation of the stationary phase and significantly
      reduced the levels of heat-induced and stationary-phase-induced thermotolerance.
      Deletion of NTH1, the gene coding for the neutral trehalase, resulted in a defect
      in trehalose mobilization during recovery from a heat shock which was paralleled
      by an abnormally slow decrease of thermotolerance. Our results provide strong
      genetic evidence that heat-induced synthesis of trehalose is an important factor
      for thermotolerance induction. In an accompanying study [Hottiger, T., De
      Virgilio, C., Hall, M. N., Boller, T. & Wiemken, A. (1993) Eur. J. Biochem. 219,
      187-193], we present evidence that the function of heat-induced trehalose
      accumulation may be to increase the thermal stability of proteins.

PMID- 8306985
TI  - The role of trehalose synthesis for the acquisition of thermotolerance in yeast.
      II. Physiological concentrations of trehalose increase the thermal stability of
      proteins in vitro.
AB  - In baker's yeast (Saccharomyces cerevisiae), accumulation of the non-reducing
      disaccharide, trehalose, is triggered by stimuli that activate the heat-shock
      response. Previously, trehalose levels have been shown to be closely correlated
      with thermotolerance, suggesting a protective function of this substance. Genetic
      evidence in support of this view is presented in an accompanying paper [De
      Virgilio, C., Hottiger, T., Dominguez, J., Boller, T. & Wiemken, A. (1993) Eur.
      J. Biochem. 219, 179-186]. In this study, we have examined the effect of
      trehalose on the thermal stability of proteins, a parameter thought to be a major
      determinant of thermotolerance. Physiological concentrations of trehalose (up to
      0.5 M) were found to efficiently protect enzymes of yeast (glucose-6P
      dehydrogenase, phosphoglucose-isomerase) as well as enzymes of non-yeast origin
      (bovine glutamic dehydrogenase, EcoRI) against heat inactivation in vitro.
      Trehalose also reduced the heat-induced formation of protein aggregates. The
      disaccharide proved to be a compatible solute, as even at very high
      concentrations (up to 1 M) it did not significantly interfere with the activity
      of test enzymes. Trehalose was at least as good or better a protein stabilizer
      than any of a number of other compatible solutes (including sugars, polyalcohols
      and amino acids), while the structurally related trehalose-6P was devoid of any
      protective effect. Thermoprotection of enzymes by trehalose was evident even in
      solutions containing high concentrations of yeast protein or substrate. The data
      indicate that trehalose accumulation may increase the thermotolerance of yeast by
      enhancing protein stability in intact cells.

PMID- 8306986
TI  - Surface potential regulation of phospholipid composition and in-out translocation
      in yeast.
AB  - In yeast cells the anionic phospholipids, phosphatidylinositol and
      phosphatidylserine, determine to a large extent the magnitude of the negative
      surface charge density (sigma) [Cerbon, J. & Calderon, V. (1990) Biochim.
      Biophys. Acta 1028, 261-267]. We now report further findings. (a) When the yeast
      phi out was reduced by increasing the concentration of monovalent (C+) or
      divalent (C2+) cations in the culture medium, the relative amount of anionic
      phospholipids increased (45-52%). (b) For each such increment, a corresponding
      increase in the external surface charge density (sigma) was found, due to the
      translocation from the cytoplasmic side to the exoplasmic side of the plasma
      membrane. (c) These changes were reversed when the phi out was increased by
      reducing the concentration of cations in the culture medium. (d) When the phi out
      was reduced and phosphatidylserine decarboxylation or phosphatidylinositol
      degradation were inhibited, to measure synthesis of anionic phospholipids, a 1.4
      times further increase in the anionic/zwitterionic phospholipid ratio occurred.
      As a consequence, a similar increase in the external surface charge (sigma) was
      found. (e) Under all the conditions studied, the percentage of anionic
      phospholipid at the external surface of the plasma membrane calculated from the
      sigma values was 2.3-3.0 times less than that in the cells, indicating that the
      asymmetric composition (more inside) was maintained. A model for the regulation
      of the anionic phospholipid composition of the yeast membranes is proposed.

PMID- 8306987
TI  - Intracellular expression of Vitreoscilla hemoglobin alters Escherichia coli
      energy metabolism under oxygen-limited conditions.
AB  - An earlier stoichiometric analysis of oxygen-limited metabolism of Escherichia
      coli expressing cloned Vitreoscilla hemoglobin (VHb) suggested improved
      efficiency of ATP production relative to wild-type controls [Khosla, C., Curtis,
      J. E., DeModena, J., Rinas, J. & Bailey, J. E. (1990) BioTechnol. 8, 849-853].
      This hypothesis has been further examined by determining several energetic
      parameters of different VHb-expressing E. coli (VHb+) strains relative to
      controls not expressing VHb (VHb-). The H+/O ratio, the transmembrane delta pH,
      and the ATP content of VHb+ constructs are 1.5, 1.6 and 2 times, respectively,
      corresponding values in VHb- controls. VHb was expressed using a low-copy-number
      vector in E. coli mutant strains lacking cytochrome o, cytochrome d, or both
      terminal oxidases; significant growth enhancement due to VHb expression was
      observed only in the strain having functional cytochrome o and lacking cytochrome
      d. All of these data obtained using different E. coli strains are consistent with
      a model of VHb action that hypothesizes enhancement by VHb of activity of the
      lower oxygen-affinity, higher proton-pumping-efficiency cytochrome o terminal
      oxidase under oxygen-limited growth conditions.

PMID- 8306988
TI  - The 100-kDa chain of nicein/kalinin is a laminin B2 chain variant.
AB  - We have isolated the basement membrane component nicein and performed rotary
      shadow analyses using electron microscopy that showed the presence of two forms
      (I and II) of the protein. Molecular cloning of the cDNA that codes for the 100
      kDa chain of the protein revealed that the sequence matches those independently
      identified for the 105-155-kDa subunit of kalinin, a recently identified basement
      membrane component. These data demonstrate that nicein and kalinin contain an
      identical chain. The length of the open reading frame in the cDNA (approximately
      5200 nucleotides) and amino acid sequence obtained from the N-terminus of the 105
      kDa kalinin chain showed the occurrence of a precursor polypeptide. This immature
      polypeptide is probably related to form I, observed by rotary shadowing, while
      the mature form is related to form II. It is noteworthy that nicein/kalinin
      subunits share discrete sequence similarities with the B2 chain of human laminin,
      but with a cleavage occurring within domain III that eliminates domains IV and V
      from the final product. The sequence of this subunit is nearly identical to that
      of B2t, a recently described polypeptide supposed to be related to a new laminin
      variant. Since nicein/kalinin expression is specifically impaired in the severe
      genodermatosis Herlitz junctional epidermolysis bullosa, the role and structure
      of this tissue-restricted laminin variant is crucial for the understanding of
      epidermal-dermal adhesion.

PMID- 8306990
TI  - Correlation of high-temperature stability of alpha-chymotrypsin with 'salting-in'
      properties of solution.
AB  - A correlation between the stability of alpha-chymotrypsin against irreversible
      thermal inactivation at high temperatures (long-term stability) and the
      coefficient of Setchenov equation as a measure of salting-in/out efficiency of
      solutes in the Hofmeister series has been found. An increase in the concentration
      of salting-in solutes (KSCN, urea, guanidinium chloride, formamide) leads to a
      many-fold decrease of the inactivation rate of the enzyme. In contrast, addition
      of salting-out solutes has a small effect on the long-term stability of alpha
      chymotrypsin at high temperatures. The effects of solutes are additive with
      respect to their salting-in/out capacities; the stabilizing action of the solutes
      is determined by the calculated Setchenov coefficient of solution. The
      correlation is explained by a solute-driven shift of the conformational
      equilibrium between the 'low-temperature' native and the 'high-temperature'
      denatured forms of the enzyme within the range of the kinetic scheme put forward
      in the preceding paper in this journal: irreversible inactivation of the high
      temperature form proceeds much more slowly compared with the low-temperature
      form.

PMID- 8306989
TI  - Reversible conformational transition gives rise to 'zig-zag' temperature
      dependence of the rate constant of irreversible thermoinactivation of enzymes.
AB  - We have obtained unusual 'zig-zag' temperature dependencies of the rate constant
      of irreversible thermoinactivation (k(in)) of enzymes (alpha-chymotrypsin,
      covalently modified alpha-chymotrypsin, and ribonuclease) in a plot of log k(in)
      versus reciprocal temperature (Arrhenius plot). These dependencies are
      characterized by the presence of both ascending and descending linear portions
      which have positive and negative values of the effective activation energy (Ea),
      respectively. A kinetic scheme has been suggested that fits best for a
      description of these zig-zag dependencies. A key element of this scheme is the
      temperature-dependent reversible conformational transition of enzyme from the
      'low-temperature' native state to a 'high-temperature' denatured form; the latter
      form is significantly more stable against irreversible thermoinactivation than
      the native enzyme. A possible explanation for a difference in thermal stabilities
      is that low-temperature and high-temperature forms are inactivated according to
      different mechanisms. Existence of the suggested conformational transition was
      proved by the methods of fluorescence spectroscopy and differential scanning
      calorimetry. The values of delta H and delta S for this transition, determined
      from calorimetric experiments, are highly positive; this fact underlies a
      conclusion that this heat-induced transition is caused by an unfolding of the
      protein molecule. Surprisingly, in the unfolded high-temperature conformation,
      alpha-chymotrypsin has a pronounced proteolytic activity, although this activity
      is much smaller than that of the native enzyme.

PMID- 8306992
TI  - Metallobiochemistry of the magnesium ion. Characterization of the essential metal
      binding site in Escherichia coli ribonuclease H.
AB  - Ribonuclease H (Escherichia coli) contains one strong magnesium-binding site, as
      determined by metal-titration experiments monitored by high field 1H-NMR and also
      by direct titration calorimetry. Kinetic and thermodynamic parameters were
      evaluated by 25Mg-NMR and were as follows: dissociation constant Kd,
      approximately 60 +/- 10 microM; activation free energy delta G*, approximately
      49.8 +/- 0.9 kJ; on/off-rate for magnesium binding Kon, approximately 1.8 x 10(8)
      M-1 s-1, koff, approximately 1.1 x 10(4) s-1; quadrupole coupling constant chi B,
      1.2 +/- 0.2 MHz. The dissociation constant was independently determined by
      standard analysis of 1H chemical shifts in magnesium-titration experiments and by
      microcalorimetry (Kd approximately 200 +/- 20 microM). Cobalt hexaamine, which
      also activates RNase H [Jou, R. & Cowan, J. A. (1991) J. Am. Chem. Soc. 113, 6685
      6686], appears to bind at the same location as Mg2+(aqueous). Assignments of C2H
      and C4H protons to specific histidine residues have been made by two-dimensional
      correlated spectroscopy experiments. Direct 25Mg-NMR pH titrations show that an
      ionizable residue (pKa approximately 5.8), most likely one of the carboxylates in
      the active site, influences magnesium binding. On the basis of the magnesium
      coordination chemistry elucidated herein, recent proposals on active-site
      chemistry are critically assessed and general physicochemical aspects of
      magnesium-binding sites on proteins and enzymes are discussed.

PMID- 8306991
TI  - Structure determination of extracellular fragments of amyloid proteins involved
      in Alzheimer's disease and Dutch-type hereditary cerebral haemorrhage with
      amyloidosis.
AB  - Amyloid deposition is a biochemical and histopathologic hallmark of various
      clinical forms of amyloidoses including Alzheimer's disease and the Dutch-type
      hereditary cerebral haemorrhage with amyloidosis. The self-aggregating peptides
      responsible for these irreversible deposits have been sequenced but the
      mechanisms involved in the aggregation processes are not well understood. In
      order to gain an understanding of the possible structures prior to self
      association, the extracellular fragment of the Alzheimer amyloid protein (beta
      A4) responsible for the deposits (the 'native' fragment) and a mutant of this
      with a single residue substitution (which is responsible for deposits in the
      Dutch-type amyloidosis) were examined by 1H-NMR spectroscopy. Interproton
      distance constraints were derived from NMR experimental data and incorporated
      into tertiary structure calculations using a simulated annealing protocol.
      Solution conformations of the fragment peptides associated with the two forms of
      amyloidoses are presented and compared. Although in both peptides the existence
      of a mixture of conformations in equilibrium is likely, one such population of
      structures possesses a flexible N-terminus and a well defined C-terminal region.
      The latter region includes a helical segment and a terminal turn-like structure.
      These structural features may be important for the basis of amyloid formation.
      Comparison of the calculated structures of the two peptides revealed a
      conformationally different region arising from the conservative substitution of
      Gln22 for Glu22. This region may be responsible for altered binding in the mutant
      peptide, giving rise to the clinically different form of amyloidosis.

PMID- 8306993
TI  - Alteration of the cleavage mode and of the transglycosylation reactions of the
      xylanase A of Streptomyces lividans 1326 by site-directed mutagenesis of the
      Asn173 residue.
AB  - The amino acid replacement of Asn173 by Asp in the xylanase A (Xln A) of
      Streptomyces lividans significantly altered its enzymic properties. A time-course
      hydrolysis of xylan showed that the altered xylanase ([N173D] Xln A) initially
      produced larger amounts of xylose (X1), xylobiose (X2) and xylotriose (X3) than
      Xln A, but less xylotetraose (X4). The bond-cleavage frequencies were determined
      for both enzymes using xylopentaose (X5), xylotetraose (X4) and xylotriose (X3)
      labelled at the reducing end of the molecule. Xln A hydrolysed X5, yielding 56%
      X2 and 44% X3, while [N173D]Xln A liberated 90% X2 and only 10% X3. Both enzymes
      hydrolysed X4 into 100% X2 and X3 into 100% X1. Transglycosylation reactions were
      detected in HPLC hydrolysis patterns using high substrate concentrations, where
      larger products than the starting substrates were formed. Their subsequent
      degradation also affected the yield of hydrolysis products. Using X5 as
      substrate, products from xylohexaose (X6) up to xylooligosides larger than
      xylooctaose (X8) were synthesized by Xln A, while [N173D]Xln A produced only a
      small amount of xyloheptaose (X7) and X8. Xln A hydrolysed X5 into an equivalent
      amount of X4 and X2 and 1.5-fold more X3. However, [N173D]Xln A yielded the same
      amount of X3 and X2 but half as much X4. With X4 as substrate, Xln A synthesized
      twofold more X7 and X6 than [N173D]Xln A. Xln A liberated 1.4-fold more X3 than
      X2, while [N173D]Xln A yielded twofold more X2 than X3. Xln A liberated almost
      fourfold more X2 than X1 from X3, while [N173D]Xln A produced only twofold more
      X2 than X1. These results indicated that the negative charge introduced by the
      mutation greatly affected the transglycosylation reaction catalysed by this
      xylanase.

PMID- 8306994
TI  - Chlorophyll synthetase cannot synthesize chlorophyll a'.
AB  - Chlorophyll synthetase catalyzes the last step of chlorophyll biosynthesis,
      namely prenylation (esterification) of chlorophyllide with phytyl diphosphate or
      geranylgeranyl diphosphate. During investigation of various chlorophyllide
      derivatives as potential substrates we observed lower esterification with
      increasing percentages of chlorophyllide a' in epimeric mixtures of
      chlorophyllides a and a'. To avoid epimerization during esterification, we
      studied the reaction in detail with model compounds [zinc-13(2)(R)-methoxy
      pheophorbide a and zinc-13(2)(S)-methoxy-pheophorbide a, zinc-13(2)(R)-methoxy
      pyropheophorbide a and zinc-chlorine6-13(1), 15(2)-dimethylester]. We conclude
      that compounds which have the 13(2)-carbomethoxy group at the same side of the
      macrocycle as the propionic side chain of ring D are neither substrates nor
      competitive inhibitors. Only compounds having the 13(2)-carbomethoxy group at the
      opposite site are substrates for the enzyme. Naturally occurring chlorophyll a'
      must be formed by epimerization after esterification.

PMID- 8306995
TI  - Molecular cloning and expression of a cDNA encoding human electron transfer
      flavoprotein-ubiquinone oxidoreductase.
AB  - Electron-transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) in the inner
      mitochondrial membrane accepts electrons from electron-transfer flavoprotein
      which is located in the mitochondrial matrix and reduces ubiquinone in the
      mitochondrial membrane. The two redox centers in the protein, FAD and a
      [4Fe4S]+2,+1 cluster, are present in a 64-kDa monomer. We cloned several cDNA
      sequences encoding the majority of porcine ETF-QO and used these as probes to
      clone a full-length human ETF-QO cDNA. The deduced human ETF-QO sequence predicts
      a protein containing 617 amino acids (67 kDa), two domains associated with the
      binding of the AMP moiety of the FAD prosthetic group, two membrane helices and a
      motif containing four cysteine residues that is frequently associated with the
      liganding of ferredoxin-like iron-sulfur clusters. A cleavable 33-amino-acid
      sequence is also predicted at the amino terminus of the 67-kDa protein which
      targets the protein to mitochondria. In vitro transcription and translation
      yielded a 67-kDa immunoprecipitable product as predicted from the open reading
      frame of the cDNA. The human cDNA was expressed in Saccharomyces cerevisiae,
      which does not normally synthesize the protein. The ETF-QO is synthesized as a 67
      kDa precursor which is targeted to mitochondria and processed in a single step to
      a 64-kDa mature form located in the mitochondrial membrane. The detergent
      solubilized protein transfers electrons from ETF to the ubiquinone homolog, Q1,
      indicating that both the FAD and iron-sulfur cluster are properly inserted into
      the heterologously expressed protein.

PMID- 8306996
TI  - Leukotriene B4 formation upon halothane-induced lipid peroxidation in liver
      membrane fractions under low O2 concentrations in vitro.
AB  - Lipid peroxidation was induced in rat liver membrane fractions in vitro upon
      NADPH-dependent metabolic activation of the anesthetic agent halothane at low O2
      concentrations. Halothane-induced lipid peroxidation was dependent on time,
      concentration of halothane, and the calculated O2 concentrations present in the
      system. Lipid peroxidation was inducible at increasing O2 concentrations up to 12
      microM, decreased at higher O2 concentrations up to 48 microM, and was not
      detectable at normoxic conditions. Leukotriene B4 (LTB4) was identified as a
      product arising upon lipid peroxidation by reverse-phase high-pressure liquid
      chromatography combined with a radioimmunoassay. LTB4 formation was maximal under
      conditions of maximal lipid peroxidation at a calculated O2 concentration of 12
      microM. Even at high concentrations, the 5-lipoxygenase inhibitors MK886 (10
      microM), ZD2138 (20 microM), and ZM230487 (20 microM) were not inhibitory in
      halothane-induced lipid peroxidation nor in the associated formation of LTB4.
      Synthetic LTB4 was transformed into its 20-hydroxy derivative by omega-oxidation
      in an O2-concentration-dependent manner, being considerably reduced at the low O2
      concentrations that maximally promoted lipid peroxidation. The collective
      evidence of these data raises the possibility that exposure to halothane might
      lead to peroxidation-associated net synthesis of LTB4 through 5-lipoxygenase
      independent escape routes in liver tissue under physiologically or
      pathophysiologically low O2 concentrations.

PMID- 8306998
TI  - The molecular forms of acetylcholinesterase from Necator americanus (Nematoda), a
      hookworm parasite of the human intestine.
AB  - Necator americanus (Nematoda: Strongyloidea), a human hookworm parasite, is known
      to release considerable amounts of acetylcholinesterase (AChE) [Pritchard, D. I.,
      Leggett K. V., Rogan, M. T., McKean, P. G. & Brown, A. (1991) Necator americanus
      secretory acetylcholinesterase and its purification from excretory/secretory
      products by affinity chromatography, Parasite Immunol. 13, 187-199]. The present
      study deals with AChE activity recovered in sequential somatic extracts, and
      excretory/secretory products, of the adult stage of the parasite. 97% of AChE was
      extractable in low-salt and high-salt detergent-free buffers, and only 3% was
      solubilised by a further extraction in the presence of Triton X-100. AChE in all
      three extracts was affected by the AChE inhibitors eserine, bis(4
      allyldimethylammoniumphenyl)pentan-3-one dibromide and edrophonium chloride, but
      was resistant to the effects of tetramonoisopropylpyrophosphortetramide, a
      butyrylcholinesterase inhibitor. Sucrose density centrifugation revealed that
      AChE in all somatic extracts (low-salt, high-salt and detergent) resolved almost
      exclusively as a single peak between 6.9-7.5 S, while excretory/secretory
      products resolved at 8.2 S. These values are all compatible with dimers of
      catalytic subunits and no evidence was found for the presence of higher oligomers
      such as asymmetric forms. The only sample to show a shift in sedimentation
      following the inclusion of detergent (Triton X-100, Brij 96) in the gradient was
      a component of the detergent-soluble extract, indicating the existence of a minor
      amphiphilic form. In low-salt-soluble and high-salt-soluble extracts, AChE was
      solubilised as a hydrophilic globular form, probably a dimeric G2. The analysis
      of diisopropylfluorophosphate-labelled extracts by SDS/PAGE, and unlabelled
      extracts by immunoblotting using a polyvalent antiserum to N. americanus AChE,
      indicated that the AChE isolated in each extract was biochemically and
      immunologically similar. The banding patterns obtained were comparable to that
      seen when purified AChE was analysed by SDS/PAGE and immunoblotted. This suggests
      that the basic catalytic subunit has a mass of 66-70 kDa with the active site
      being located in a 30-kDa domain. All experimental data indicate the existence of
      only one AChE class in Necator homologous to AChE of class B from Caenorhabditis
      elegans. The solubility characteristics and globular nature of this hookworm AChE
      suggest that its major function is as an excretory or secretory product. This
      again raises the question of the true biological function of this 'non
      cholinergenic' nematode secretion.

PMID- 8306997
TI  - Low-frequency stimulation of rat fast-twitch muscle enhances the expression of
      hexokinase II and both the translocation and expression of glucose transporter 4
      (GLUT-4).
AB  - This study followed changes in the capacities of uptake and phosphorylation of
      glucose in response to contractile activity in low-frequency stimulated (10Hz, 24
      h/d) rat fast-twitch muscle. We investigated the intracellular distribution of
      GLUT-4, the major glucose transporter isoform in muscle, changes in the amounts
      of its specific mRNA and total cellular protein, as well as changes in its
      relative synthesis rate. These analyses were complemented by measurements of
      total hexokinase activity and hexokinase II (HKII) expression at the levels of
      mRNA content and protein synthesis. Changes in protein synthesis were determined
      by in vivo labeling with [35S]methionine. Translocation of GLUT-4 into the
      sarcolemma was an immediate response to contractile activity, whereas changes in
      its total amount were observed only with ongoing stimulation (5 d and longer). A
      twofold increase in GLUT-4 content after 5 d and longer stimulation periods was
      preceded by elevations of its mRNA and by enhanced [35S]methionine incorporation.
      Conversely, increases in HKII expression with a rise in total hexokinase activity
      occurred soon after the onset of stimulation (30-fold elevations of HKII mRNA
      after 12 h and 20-fold increases in [35S]methionine incorporation after 24 h).
      With ongoing stimulation, HKII mRNA and synthesis returned to lower levels
      (fivefold elevations). Nevertheless, hexokinase activity continued to rise,
      stabilizing at fivefold-elevated levels after 3 d. These observation suggested
      that posttranscriptional mechanisms contributed to the upregulation of HKII, e.g.
      stabilization by elevated intracellular glucose and mitochondrial binding of the
      enzyme. This suggestion was supported by experiments with cessation after 24 h
      where hexokinase activity continued to increase, although the mRNA content and,
      especially, the [35S]methionine incorporation decayed steeply. The increase in
      HKII prior to GLUT-4 suggests that phosphorylation may be rate limiting in
      glucose utilization of glycolytic fibers under conditions of sustained
      contractile activity. Taken together, the changes in distribution and content of
      GLUT-4, as well as in HKII represent early metabolic adaptations. In addition,
      they are related to the overall process of stimulation-induced fiber type
      transformation.

PMID- 8306999
TI  - Photoaffinity labelling of cardiac membrane GTP-binding proteins in response to
      insulin.
AB  - Plasma membranes from rat cardiac ventricular tissue and insulin receptors
      partially purified by wheat-germ-agglutinin chromatography were subjected to
      direct photoaffinity labelling with [alpha-32P]GTP in order to elucidate the
      presence of insulin-receptor-coupled GTP-binding proteins. In plasma membranes
      three proteins have been identified that exhibit an enhanced photolabelling with
      the nucleotide in response to insulin. The apparent molecular masses of these
      proteins were found to be 56, 60 and 74 kDa. Photolabelling of partially purified
      insulin receptors showed the copurification of the 60-kDa species, whereas the 56
      kDa and 74-kDa proteins could not be detected. Furthermore, the 60-kDa G-protein
      was found to be specifically co-immunoprecipitated with the insulin receptor.
      Incubation of insulin receptors with insulin increased the labelling of the 60
      kDa band to 205 +/- 27% (n = 5) of control. Immuno- and ligand-blotting
      experiments revealed the additional presence of a 39-kDa G(o)-like protein and
      two G-proteins with molecular masses of 24 and 26 kDa in the receptor
      preparation. Under basal conditions the insulin receptor and the 60-kDa G-protein
      exhibited an apparent inverse distribution between plasma and microsomal
      membranes with the G-protein being extensively labelled in the microsomal
      fraction. In conclusion, our data show that, in its native environment, the
      cardiac insulin receptor couples to at least three GTP-binding proteins. Out of
      these, a 60-kDa species of microsomal origin, copurifies with the insulin
      receptor. It is suggested that this G-protein is associated with the insulin
      receptor and may be involved in insulin receptor signalling in target cells.

PMID- 8307000
TI  - Glycosylation of two recombinant human uterine tissue plasminogen activator
      variants carrying an additional N-glycosylation site in the epidermal-growth
      factor-like domain.
AB  - Recombinant human uterine tissue plasminogen activator (tPA) glycosylation
      mutants carrying an additional N-glycosylation site in the epidermal-growth
      factor-like domain due to the replacement of either Tyr67 by Asn (YN-tPA) or
      Gly60 by Ser (GS-tPA) were expressed in mouse epithelial cells (C127) in the
      presence of [6-3H]glucosamine. Glycopeptides comprising individual glycosylation
      sites were isolated and oligosaccharides attached were liberated by treatment
      with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta
      glucosaminyl)asparagine amidase F. Oligosaccharide alditols obtained after
      reduction were either directly characterized by high-pH anion-exchange
      chromatography (high-mannose and hybrid-type glycans) or preparatively
      subfractionated after enzymic desialylation and separation from sulphated
      asialooligosaccharides (complex-type sugar chains). Individual (sub)fractions of
      glucans were studied by methylation analysis, liquid secondary-ion mass
      spectrometry and, in part, by exoglycosidase digestion, whereas corresponding
      deglycosylated peptides were identified by amino acid analysis and N-terminal
      amino acid sequencing. The results revealed that Asn117 of YN-tPA carried
      exclusively high-mannose-type glycans with five to nine mannose residues similar
      to wild-type tPA expressed in this cell line [Pfeiffer, G., Schmidt, M., Strube,
      K.-H. & Geyer, R. (1989) Eur. J. Biochem. 186, 273-286]. In contrast, Asn117 of
      GS-tPA carried only small amounts (about 25%) of high-mannose and hybrid-type
      species and predominantly complex-type sugar chains (about 75%) which were
      partially incomplete and mostly devoid of fucose. Newly introduced N
      glycosylation sites at Asn67 (YN-tPA) or Asn58 (GS-tPA) as well as those at
      Asn184 and Asn448 were solely substituted by complex-type glycans. Each
      carbohydrate attachment site displayed a peculiar oligosaccharide pattern with
      regard to branching and substitution by Gal alpha 3-residues, sulphate groups,
      intersecting GlcNAc and lactosamine repeats. Our study clearly demonstrates that
      creation of a new glycosylation site at Asn58 influenced the oligosaccharide
      processing and, hence, the glycosylation pattern at Asn117, whereas introduction
      of a new site at Asn67 did not. The relative amounts of complex-type glycans at
      Asn117 of GS-tPA correlated with the degree of carbohydrate substitution of
      Asn58. Therefore, it can be concluded that the presence of a sugar chain at the
      position and not the Gly to Ser mutation itself is responsible for the observed
      alteration of GS-tPA glycosylation.

PMID- 8307001
TI  - The involvement of polyamines in the activation of vitamin D receptor from
      porcine intestinal mucosa.
AB  - In the intracellular process of the action of calcitriol, vitamin D receptor is
      thought to undergo some kind of physiochemical change, called activation, before
      the receptor binds to the vitamin D response element of the gene. In this paper,
      the effects of polyamines and their analogues on the sedimentation properties of
      vitamin D receptor prepared from porcine intestinal mucosa, and on DNA binding
      activity of the receptor, were studied. In sucrose density gradient analysis,
      polyamines decreased the sedimentation coefficient of vitamin D receptor in a
      dose-dependent fashion. Polyamines increased DNA binding activity of vitamin D
      receptor dose-dependently. These findings show that polyamines can activate
      vitamin D receptor in vitro. Among naturally existing polyamines, spermidine and
      spermine, but not putrescine, were effective within their physiological
      intracellular concentrations, suggesting that both spermidine and spermine can
      activate vitamin D receptor in vivo as well. Sucrose density gradient analysis
      using various kinds of polyamine analogues having various numbers of cations
      showed that the number of cation of polyamines is important for the efficiency to
      change the sedimentation coefficient of vitamin D receptor, and that the distance
      between two cationic charges does not play an important role.

PMID- 8307002
TI  - Characterisation of a trisulphide derivative of biosynthetic human growth hormone
      produced in Escherichia coli.
AB  - A novel protein derivative has been found during process development of
      biosynthetic human growth hormone; it has been characterised as human growth
      hormone with a Cys182-Cys189 trisulphide bridge. We have not been able to find a
      previous report in the literature about this kind of derivative. The
      characterisation was obtained partly on the full-length derivative and partly on
      a tryptic fragment of the derivative. The full-length derivative was
      characterised by reduction with 1,4-dithiothreitol followed by electrospray mass
      spectrometry, treatment with cysteine and measurement of hydrogen sulphide
      liberation upon cysteine treatment. The tryptic fragment from peptide mapping was
      characterised by amino acid analysis, amino acid sequencing and mass
      spectrometry. All data indicated an extra sulphur atom in the Cys182-Cys189
      cystine bridge.

PMID- 8307003
TI  - Molecular cloning and expression of chick embryo Gal beta 1,4GlcNAc alpha 2,6
      sialyltransferase. Comparison with the mammalian enzyme.
AB  - DNA clones encoding beta-galactoside alpha 2,6-sialyltransferase have been
      isolated from chick embryonic cDNA libraries using sequence information obtained
      from the conserved amino acid sequence of the previously cloned enzymes. The cDNA
      sequence revealed an open-reading frame coding for 413 amino acids, and the
      deduced amino acid sequence showed 57.6% identity with the sequence of rat liver
      Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase. The primary structure of this
      enzyme suggested a putative domain structure, similar to structures found in
      other glycosyltransferases, consisting of a short N-terminal cytoplasmic domain,
      a signal-membrane anchor domain, a proteolytically sensitive stem region and a
      large C-terminal active domain. The identity of this enzyme was confirmed by
      construction of a recombinant sialyltransferase in which the N-terminus part
      including the cytoplasmic tail, signal anchor domain and stem region was replaced
      with an immunoglobulin signal peptide sequence. The expression of this
      recombinant protein in COS-7 cells resulted in secretion of a catalytically
      active and soluble form of the enzyme into the medium. The expressed enzyme
      exhibited activity only towards the disaccharide moiety of Gal beta 1,4GlcNAc in
      glycoproteins.

PMID- 8307004
TI  - Characterization of native laminin from bovine kidney and comparison with other
      laminin variants.
AB  - A comprehensive characterization of laminin isoforms requires access to native
      preparations of laminins of a defined subunit composition. For this purpose an
      optimized isolation procedure was developed and shown to be broadly applicable to
      normal mammalian tissues. The protocol does in addition yield side fractions
      highly enriched in collagens XII and XIV. The major laminin purified from bovine
      kidney is indistinguishable from mouse Engelbreth-Holm-Swarm (EHS) tumor laminin
      in electron microscopy, but contains an A chain that migrates in a position
      intermediate to the Ae and the Am chains on SDS/PAGE. Antisera raised against
      mouse EHS-tumor laminin crossreact with B chains, but not with the A chain, of
      kidney laminin. Further, this A chain is not recognized by antisera raised
      against the Am chain. Laminins from heart and kidney both contain a significant
      subpopulation with a 190-kDa polypeptide identified as the B1s chain. The Am
      containing laminins from heart and placenta differ morphologically from the Ae
      containing EHS laminin in having one short arm that does not have the
      characteristic globule-rod-globule appearance. Further, the Am-containing
      laminins show a significantly higher thermal stability of the coiled-coil alpha
      helical region in the long arm than does Ae-containing EHS laminin, indicating
      that certain combinations of laminin chains interact more strongly than others.

PMID- 8307005
TI  - Purification, characterization and inhibition of dihydropyrimidinase from rat
      liver.
AB  - Dihydropyrimidinase (DHPase) was purified 564-fold over the initial rat liver
      extract, using heat, ammonium sulfate fractionation, DEAE-Sepharose CL-6B,
      carboxymethyl-Sepharose CL-6B, hydroxyapatite and Sephacryl S-300 chromatography.
      The purified enzyme was shown to be homogeneous by gel electrophoresis both in
      the presence and absence of SDS. Its molecular mass, determined by gel
      filtration, was 215 kDa and the subunit mass was 54 kDa. DHPase catalyzed the
      reversible cyclization of 5,6-dihydrouracil (H2Ura) to N-carbamoyl-beta-alanine
      or 5,6-dihydrothymine (H2Thy) to N-carbamoyl-beta-aminoisobutyric acid. Authentic
      5-bromo-5,6-dihydrouracil (BrH2Ura) and commercially available H2Thy were
      racemic. However, these 5-substituted 5,6-dihydropyrimidines were hydrolyzed by
      over 96% and 98%, respectively, by DHPase. These results suggest that
      dihydropyrimidinase has no stereo specificities for 5-substituents of H2Ura. The
      addition of H2Ura and H2Thy competitively inhibited the enzyme activity against
      BrH2Ura. However, the addition of N-carbamoyl-beta-alanine or N-carbamoyl-beta
      amino-isobutyric acid showed hyperbolic mixed-type inhibition, when BrH2Ura was
      used as the substrate. The values of the dissociation constants of BrH2Ura, N
      carbamoyl-beta-alanine and N-carbamoyl-beta-aminoisobutyric acid were 17 microM,
      0.38 mM and 0.38 mM, respectively. DHPase from the rat liver contains 4 mol
      Zn2+/mol active enzyme, presumably one atom/subunit. Zn2+ also inhibited the
      hydrolysis of BrH2Ura by the enzyme. The Ki for Zn2+ as an inhibitor of DHPase
      was 23 microM, and the maximum rate of inactivation was 0.057 min-1 at 37 degrees
      C. H2Ura and H2Thy protected the enzyme activity from Zn2+ inactivation.

PMID- 8307006
TI  - Hepatocyte growth factor elevates the activity levels of glycolipid
      sulfotransferases in renal cell carcinoma cells.
AB  - Accumulation of sulfoglycolipids associated with markedly elevated activity
      levels of glycolipid sulfotransferases has previously been demonstrated in the
      human renal cell carcinoma cell line, SMKT-R3. To elucidate the regulatory
      mechanisms of sulfoglycolipid synthesis in SMKT-R3 cells, the effects of various
      growth factors on the metabolic enzymes of sulfoglycolipids were investigated.
      Hepatocyte growth factor (HGF) significantly increased the activity levels of the
      sulfotransferases in a dose-dependent manner, but did not change that of
      arylsulfatase A, which hydrolyzes sulfoglycolipids. Scatchard analysis of 125I
      HGF binding to SMKT-R3 cells indicated that the cells expressed high-affinity
      receptors for HGF with a Kd of 36 pM and 750 sites/cell. Furthermore, metabolic
      labeling with [35S]sulfate revealed that the addition of HGF to the culture
      medium of the cells resulted in an increment of sulfoglycolipid synthesis.
      Therefore, these observations suggest that HGF can function as a regulatory
      factor in sulfoglycolipid synthesis through the modulation of the
      sulfotransferase activity levels in renal cell carcinoma cells. In addition, HGF
      stimulated the proliferation and motility of SMKT-R3 cells, suggesting that HGF
      has multiple biological activities in renal cell carcinoma cells.

PMID- 8307007
TI  - Purification, cDNA cloning and heterologous expression of human phosphomannose
      isomerase.
AB  - Phosphomannose isomerase catalyses the interconversion of fructose-6-P and
      mannose-6-P and has a critical role in the supply of D-mannose derivatives
      required for many eukaryotic glycosylation reactions. Three classes of enzymes
      possessing phosphomannose-isomerase activity have been identified in bacteria and
      lower eukaryotes. We have purified human phosphomannose isomerase to homogeneity
      from placental tissue. Protein sequence information obtained from internal
      fragments of the protein was used to design degenerate oligonucleotides which
      were used to amplify a fragment of a human phosphomannose-isomerase cDNA. A full
      length cDNA was isolated from a human testes lambda gt11 library using this
      fragment as a probe. The cDNA encoded a protein with significant sequence
      identity to fungal and some bacterial phosphomannose isomerases but was unrelated
      to those from other bacteria. Based on amino acid sequence identity we propose a
      classification system for enzymes with phosphomannose-isomerase activity. The
      cDNA, under the control of the GAL1 promoter, was expressed in a Saccharomyces
      cerevisiae strain from which the native gene encoding phosphomannose isomerase
      had been deleted. The human enzyme was found to be able to functionally
      substitute for the yeast enzyme. Phosphomannose-isomerase mRNA was found in all
      human tissues tested but was more highly expressed in heart, brain and skeletal
      muscle. The cDNA was expressed in Escherichia coli permitting the isolation of
      pure recombinant protein which will be used for kinetic and structural studies.

PMID- 8307008
TI  - Biosynthesis of carnosine and related peptides by skeletal muscle cells in
      primary culture.
AB  - Synthesis of carnosine (beta-alanyl-L-histidine) and related dipeptides could be
      demonstrated in primary muscle cell cultures derived from embryonic chick
      pectoral muscle. After incubation with radiolabeled beta-alanine or gamma
      aminobutyric acid, the radiolabeled dipeptides were isolated from the cell
      extracts and also in small amounts from the culture medium. The kinetics of
      dipeptide formation indicated that anserine (beta-alanyl-1-methylhistidine) is
      not formed directly by these cells but as a secondary product via the methylation
      of carnosine. Coinciding with the morphological differentiation of the
      mononucleated myoblast to form multi-nucleated myotubes, a rapid increase in beta
      alanine uptake and also in dipeptide synthesis could be observed. These results
      demonstrate that carnosine and related peptides are not merely deposited in
      skeletal muscles but that they are actively synthesized by muscle cells in
      culture.

PMID- 8307009
TI  - Discrimination against misacylated tRNA by chloroplast elongation factor Tu.
AB  - Chloroplast elongation factor Tu was purified from Pisum sativum and the binding
      properties of glutamylated chloroplast tRNAs were studied by gel-permeation
      chromatography. Whereas chloroplast Glu-tRNA(Glu) is efficiently bound by this
      factor, the misacylated Glu-tRNA(Gln) does not interact with chloroplast
      elongation factor Tu.GTP and is thus efficiently excluded from protein synthesis.
      Comparison with the behaviour of Escherichia coli elongation factor Tu.GTP shows
      that this factor, which is not confronted with the in vivo misacylation
      phenomenon of organelles, binds both Glu-tRNA(Glu) and Glu-tRNA(Gln) from
      chloroplasts with approximately equal efficiency.

PMID- 8307010
TI  - Isolation and complete sequence of CBR, a gene encoding a putative cytochrome b
      reductase in Saccharomyces cerevisiae.
AB  - We have isolated and characterised a novel yeast gene, CBR (cytochrome b
      reductase), encoding a 35-kDa yeast novobiocin-binding protein. The predicted
      protein sequence of CBR displays considerable similarity to both plant nitrate
      reductases and mammalian cytochrome b5 reductases indicating that it is a
      putative member of the flavoprotein pyridine-nucleotide-cytochrome-reductase
      family. Disruption of CBR is not lethal under various growth conditions,
      suggesting the presence of some functional overlap with other reductases,
      possibly with the cytochrome P-450 reductase.

PMID- 8307011
TI  - Purification and characterization of ATBP, a novel protein that binds to A/T
      stretches in three segments of the Sarcophaga lectin gene.
AB  - A DNA-binding protein for the Sarcophaga lectin gene, ATBP (A/T-stretches-binding
      protein) was purified to homogeneity from the nuclear extract of NIH-Sape-4
      cells. The molecular mass of ATBP determined under denaturing conditions was 53
      kDa, but its native molecular mass estimated by gel-filtration chromatography was
      430 kDa, suggesting that it is an octamer of the 53-kDa subunit. This protein
      bound to at least three DNA fragments from the Sarcophaga lectin gene, two of
      them are in the 5'-upstream region and the other is in a region containing an
      intron. These fragments are very AT rich and inlaid with stretches of A or T
      residues (A/T stretches). ATBP was found to have affinity for poly[d(A-T)]. These
      results suggest that ATBP binds to A/T stretches in the three DNA fragments from
      this gene. Furthermore, longer DNA was found to be bound more effectively,
      suggesting that an octamer of the 53-kDa subunit has multiple binding sites for
      the DNA fragments and requires a relatively long DNA sequence for binding.

PMID- 8307012
TI  - Expression, purification and characterization of the recombinant kringle 2 and
      kringle 3 domains of human plasminogen and analysis of their binding affinity for
      omega-aminocarboxylic acids.
AB  - The kringle 2 (E161T/C162S/EEE[K2HPg/C169S]TT) and the kringle 3 (TYQ[K3HPg]DS)
      domains of human plasminogen (HPg) were expressed in Escherichia coli in an
      expression vector with the phage T5 promotor/operator element N250PSN250P29 and
      the cDNA sequence for a hexahistidine tail to facilitate the isolation of the
      recombinant protein. A coagulation factor Xa (FXa)-sensitive cleavage site was
      introduced to remove the N-terminal histidine tag. In r-K2, mutations E161T and
      C162S were introduced to enhance the FXa cleavage yield and C169S to replace the
      cysteine residue, participating in the inter-kringle disulfide bridge between
      kringles 2 and 3. Recombinant proteins were isolated by affinity chromatography
      on Ni(2+)-nitrilotriacetic acid/agarose and refolded under denaturing and
      reducing conditions followed by a non-denaturing and oxidising environment. The
      free thiol group in position 297 in r-K3 was selectively alkylated with
      iodoacetamide. The hexahistidine tail was successfully removed with FXa. The N
      terminal sequence, the amino acid composition and the molecular mass analyses are
      in agreement with the expected data. The correct arrangement of the disulfide
      bonds was verified by sequence analysis of the corresponding thermolytic and
      subtilisin fragments. r-K2 exhibits weak binding to lysine-Bio-Gel. The weak
      binding affinity of r-K2 for omega-aminocarboxylic acids is confirmed by
      intrinsic fluorescence titration with 6-aminohexanoic acid (NH2C5COOH) indicating
      a Kd of approximately 401 microM. In contrast, r-K3 seems to be devoid of a
      binding affinity for omega-aminocarboxylic acids. Considering earlier determined
      Kd values of kringle 1, kringle 4 and kringle 5, the binding affinity of HPg
      kringle domains for NH2C5COOH is proposed to decrease in the following order,
      kringle 1 > kringle 4 > kringle 5 > kringle 2 > kringle 3.

PMID- 8307013
TI  - In vivo incorporation of copper into the iron-exchangeable and manganese
      exchangeable superoxide dismutase from Propionibacterium shermanii. Amino acid
      sequence and identity of the protein moieties.
AB  - Propionibacterium shermanii, an aerotolerant anaerobe, produces an iron
      containing or a manganese-containing superoxide dismutase, depending on the metal
      supplied in the culture medium [Meier, B., Barra, D., Bossa, F., Calabrese, L. &
      Rotilio, G. (1982) J. Biol. Chem. 257, 13977-13980]. In this study, we
      demonstrate in vivo incorporation of copper into an active superoxide-dismutase
      protein when iron and manganese are absent from the growth medium. Superoxide
      dismutases containing either iron, manganese or copper were isolated from P.
      shermanii, their complete amino acid sequences were determined and the identity
      of their protein moieties was established. The polypeptide chain is made up of
      201 amino acid residues, corresponding to a molecular mass of 22.6 kDa. From
      sedimentation equilibrium experiments, the native protein shows a molecular mass
      of approximately 86 kDa and therefore consists of four identical subunits. The
      primary structure was compared with the structure of other Fe-superoxide
      dismutases and Mn-superoxide dismutases, in particular those possessing a strict
      metal cofactor specificity.

PMID- 8307014
TI  - Mechanisms involved in serum-dependent inactivation of the immunotoxin enhancers
      monensin and carrier-protein-monensin.
AB  - The immunotoxin-enhancing properties of monensin and of human-serum-albumin
      monensin conjugates are severely impaired in the presence of human serum. In this
      study we have therefore investigated the interaction between serum proteins and
      monensin leading to the inactivation of monensin function as immunotoxin
      potentiator. We found that the binding of monensin-specific mAb to thioether
      cross-linked or disulfide-cross-linked protein-monensin conjugates is negatively
      affected by serum, as indicated by immunoenzymic (ELISA) and radioimmunobinding
      analysis. Size-exclusion chromatography of serum samples indicated that the
      greatest blocking effect is due to protein components of 40-90 kDa eluting as a
      broad peak (peak 4). Analysis of the proteins contained within peak 4 by ion
      exchange chromatography followed by microsequencing revealed that the major
      components of peak no. 4 were transferrin, human serum albumin and immunoglobulin
      fragments. Investigations on the nature of the interactions between serum
      proteins and monensin leading to monensin inactivation were conducted by affinity
      chromatography of serum on immobilized human-serum-albumin-monensin conjugates,
      size-exclusion chromatography, SDS/PAGE analysis of serum-treated human-serum
      albumin-monensin conjugates, and evaluation of the stability of immobilized human
      serum-albumin-bound 125I-monensin following treatment with serum. Addition of
      esterase inhibitors (e.g. EDTA, 4-nitrophenyl phosphate) or prior treatment of
      the serum at 56 degrees C partially reversed the serum effects observed. We
      conclude that serum proteins block the immunotoxin-enhancing effect of monensin
      and of human-serum-albumin-monensin conjugates by multiple mechanisms involving
      hydrophobic and covalent interactions and enzyme-mediated cleavage of protein
      bound monensin.

PMID- 8307015
TI  - Lead-ion-induced cleavage of RNase P RNA.
AB  - Pb(2+)-induced hydrolysis of RNase P RNAs from Escherichia coli and the
      thermophilic eubacterium Thermus thermophilus HB8 revealed one prominent site
      specific cleavage in the two RNAs and several minor cleavage sites in
      structurally corresponding regions of both RNAs. Data presented here and in a
      previous study [Kazakov, S. & Altman, S. (1991) Proc. Natl Acad. Sci. USA 88,
      9193-9197] provide evidence for several ubiquitous metal-ion-binding sites in
      eubacterial RNase P RNA subunits. With the T. thermophilus RNase P RNA,
      susceptibility to Pb(2+)-induced strand scission at the most prominent site was
      hypersensitive at the temperature of highest enzyme activity (55 degrees C). Pb2+
      hydrolysis at this site was strongly reduced at a temperature of 37 degrees C,
      where processing is also inefficient. For E. coli RNase P RNA, specific changes
      in the lead hydrolysis pattern were observed due to the presence of excess tRNA.
      Thus, Pb(2+)-induced hydrolysis seems suitable to sense different conformations
      of RNase P RNAs. The T. thermophilus RNase P RNA, in particular, displayed
      significant processing activity after severe fragmentation by Pb2+, and therefore
      appears to be suited for reconstituting an active enzyme from RNA subfragments.

PMID- 8307016
TI  - The mercury(II) and high-salt-induced conformational B<==>Z transitions of
      poly[d(G-m5C).d(G-m5C)] as studied by non-polarized (ultraviolet) and circularly
      polarized (CD) ultraviolet spectroscopy.
AB  - The B<==>Z transition of poly[d(G-m5C).d(G-m5C)] in buffered solution (0.002 M
      sodium cacodylate, pH 7) was studied by CD and ultraviolet spectroscopy as a
      function of the supporting electrolyte concentration (0.002-1.1 M NaClO4) in the
      absence of Hg(ClO4)2 [Hg(II)], and as a function of the Hg(II) concentration at a
      given NaClO4 level. NaClO4 alone changes the conformation of the polymer from
      B<==>Z at approximately 0.7 M NaClO4. The spectral changes caused by Hg(II) in
      the B-form polymer (e.g. at 0.002 M < or = [Na] < or = 0.7) resemble those
      generated by salt alone during the B<==>Z transition; the changes generated by
      Hg(II) in the Z-form polymer (e.g. in 1.1 M [Na]) leave principally intact the Z
      form spectrum obtained at the higher levels of NaClO4 (e.g. at [Na] > 0.7 M) in
      the absence of Hg(II). It is concluded that particularly the long-wavelength
      positive-CD band, located at 274 nm, is a correct indicator of duplex DNA
      right<==>left-screwness inversion. According to generally accepted criteria, the
      NaClO4-induced left-handed form is Z DNA; Hg(II) generates a left-handed form
      termed here ZHg(II). This form is close to (but not identical with) the salt
      induced Z-form. All Hg(II)-induced spectral changes are reversible upon removal
      of Hg(II) with a suitable complexing reagent (e.g. NaCN).

PMID- 8307018
TI  - Purification and characterization of erythrocyte caldesmon. Hypothesis for an
      actin-linked regulation of a contractile activity in the red blood cell membrane.
AB  - We have previously shown that in human or pig whole erythrocytes, only a single
      71-kDa polypeptide cross-reacts with the affinity-purified antibody to pig
      platelet caldesmon (der Terrossian et al., 1989). In the present paper, we
      demonstrate that this polypeptide represents a genuine caldesmon which remains
      attached to the membrane prepared in the presence of an excess of free Mg2+ but
      not in its absence. Immunoreactivity of this peptide is specific towards the
      antibody to pig platelet caldesmon since it is not labelled with antibodies to
      other components of the red cell membrane. Erythrocyte caldesmon was purified to
      95% homogeneity and displays well known characteristics of caldesmons from other
      sources. Together with tropomyosin, it has the ability to regulate platelet actin
      activated rabbit skeletal muscle myosin ATPase activity. The stoichiometry of 1
      caldesmon/1 tropomyosin/7-9 actin molecules indicates that the amount of
      caldesmon, in the red cell membrane, corresponds precisely to the amount of
      tropomyosin. Immunofluorescent labelling of whole erythrocytes gave similar
      punctate patterns with purified antibodies to myosin, to caldesmon, to
      tropomyosin and to actin (but not to spectrin), suggesting colocalization of
      these proteins. Together, and for the first time, our results give strong
      evidence that caldesmon, bound on the actin protofilament, might represent the
      inhibitory component, so far uncharacterized, of a thin-filament-like system in
      erythrocyte.

PMID- 8307017
TI  - Expression and characterization of recombinant human and rat liver 6-pyruvoyl
      tetrahydropterin synthase. Modified cysteine residues inhibit the enzyme
      activity.
AB  - 6-Pyruvoyl-tetrahydropterin synthase is the rate-limiting enzyme in the synthesis
      of human tetrahydrobiopterin, a cofactor for several hydroxylases involved in
      catecholamine and serotonin biosynthesis. The human and rat liver cDNAs encoding
      the 16-kDa subunit of 6-pyruvoyl tetrahydropterin synthase were expressed as
      maltose-binding-6-pyruvoyl-tetrahydropterin-synthase fusion proteins. After
      cleavage from the fusion protein, the human and rat enzymes were purified to
      homogeneity. Apparent Km for the substrate dihydroneopterin triphosphate (8.5
      microM for the human and 8.0 microM for the rat enzyme), pI (4.6 and 4.8) and
      heat stability of the recombinant enzymes were similar to the native enzymes. The
      specific activity of the enzymes was enhanced up to fourfold in the presence of
      dithiothreitol during purification. The modification of the only cysteine residue
      in rat 6-pyruvoyl tetrahydropterin synthase, which is conserved in the human
      enzyme, inhibited its activity up to 80%. Modification under non-reducing
      conditions of both cysteine residues of the human enzyme by N-ethylpyridine
      resulted in a 95% loss of enzyme activity. This demonstrates that the two
      cysteines are not linked by disulfide bridges but rather involved in catalysis.
      Cross-linking experiments and analysis by gel electrophoresis showed
      predominantly trimeric and hexameric forms of the recombinant enzymes from both
      species suggesting that the native form is a homohexamer of 98 kDa, for the
      human, and 95 kDa, for the rat enzyme, composed of two trimeric subunits.

PMID- 8307019
TI  - A 40-kDa myelin basic protein kinase, distinct from erk1 and erk2, is activated
      in mitotic HeLa cells.
AB  - Mitotic HeLa cells showed an increased phosphorylation activity towards myelin
      basic protein compared to cells in G1 or S phases. Further investigation using
      renaturation gels revealed that, in mitotic cell lysates, a protein with an
      apparent molecular mass of around 40 kDa phosphorylates myelin basic protein.
      This kinase is active early in mitosis, but is then downregulated concomitantly
      with p34cdc2 kinase as mitosis proceeds, its activity decreasing to basal levels
      by early G1. The molecular mass of the kinase suggested that it might be one of
      the human homologues of rat erk1 or erk2. However, antibodies raised against C
      terminal sequences of erk1 and erk2 failed to immunoprecipitate renaturable
      kinase activity from mitotic lysates. In addition, in immunoblots erk1 and erk2
      failed to show the well established changes in electrophoretic migration that are
      consequences of their activation. These data indicate that these two mitogen
      activated protein (MAP) kinases are not stimulated during HeLa cell mitosis and
      indicate that the 40-kDa kinase is either a new member of the MAP kinase family
      or it is a novel mitotic kinase that has not yet been described.

PMID- 8307020
TI  - Functional differences in the promoters of the interferon-inducible (2'-5')A
      oligoadenylate synthetase and 6-16 genes in interferon-resistant Daudi cells.
AB  - A clone of interferon-alpha-resistant (IFNr) Daudi cells retained much greater
      transcriptional inducibility of the (2'-5') oligoadenylate synthetase than the 6
      16 gene despite the fact that the response of both genes is mediated by highly
      similar interferon-stimulable DNA response elements (ISRE). The primary IFN-alpha
      activatable transcription factor E (ISGF3) and the additional IFN-alpha-inducible
      ISRE-binding complex M were greatly reduced in the IFNr cells. The defect in E
      was in the E alpha subunit. In electrophoretic mobility-shift assays the 6-16 and
      (2'-5') oligoadenylate synthetase ISRE competed approximately equivalently for E
      and M. Moreover although active in wild-type cells the (2'-5') oligoadenylate
      synthetase ISRE was no more capable of conferring inducibility on a reporter gene
      in the IFNr cells than was the 6-16 ISRE. The contrasting response of the
      endogenous (2'-5') oligoadenylate synthetase and 6-16 genes in the IFNr cells is,
      therefore, unlikely simply to reflect the slight difference in the sequence of
      their ISRE. Consistent with this, in addition to the ISRE, sequences 5' to the
      ISRE in the (2'-5') oligoadenylate synthetase promoter appeared necessary for
      good induction by IFN alpha in the IFNr cells. Subtle quantitative changes in the
      phenotype of the IFNr cells have, however, precluded a more precise definition of
      the DNA element(s) involved.

PMID- 8307021
TI  - Cloning and characterization of the gene for the catalytic subunit of cAMP
      dependent protein kinase in the aquatic fungus Blastocladiella emersonii.
AB  - We have isolated and characterized cDNA and genomic DNA clones encoding the
      catalytic subunit (C) of cAMP-dependent protein kinase in the aquatic fungus
      Blastocladiella emersonii. The C-subunit amino acid sequence derived from the
      nucleotide sequence predicts a basic polypeptide of 424 residues, excluding the
      initiator methionine, which by amino-terminal sequence analysis has been shown to
      be absent from the mature protein. The Blastocladiella C presents a 70-amino-acid
      extension at the amino terminus, when aligned to the mouse C alpha subunit, being
      one of the largest C subunits already characterized. The B. emersonii C-gene
      coding region is interrupted by three introns, ranging in size over 57-69 bp. The
      positions of the introns are quite different from those found in other species,
      suggesting a considerable amount of evolutionary drift in the gene structure. The
      5'-flanking region lacks recognizable TATA or CCAAT sequences, is remarkably high
      in GC content (70%), and primer extension experiments indicate that transcription
      initiates from multiple sites. Several sequence motifs were identified in the
      promoter region which could be involved in the developmental control of this
      gene.

PMID- 8307022
TI  - Heat shock enhances the amount of prenylated Dnaj protein at membranes of
      glyoxysomes.
AB  - Proteins similar to the bacterial Dnaj protein have been implicated as molecular
      chaperones in different compartments of eukaryots. A plant equivalent is now
      described in tissues of dark-grown cucumber seedlings. Using a cucumber Dnaj
      protein produced by expression in bacteria, we raised polyclonal antibodies
      against the protein and used them for localization studies. In etiolated cucumber
      seedlings, both cotyledons and hypocotyledons were found to contain Dnaj
      proteins. Cell fractionation of etiolated cotyledons showed that Dnaj proteins
      were detectable mainly in the postnuclear cell fraction after sedimentation at
      10,000 x g, and in the microsomes. Following subfractionation by sucrose density
      gradient centrifugation and analysis by immunoblotting, a 53-kDa protein was
      attributed to the glyoxysomal fraction and an 80-kDa protein to the mitochondrial
      fraction. The glyoxysomal Dnaj protein behaved as a membrane-bound form. Upon
      heat shock, a slight increase in the content of the glyoxysomal Dnaj protein was
      found. When glyoxysomes were treated with protease and subsequently isolated by
      gradient centrifugation, virtually all immunologically detectable Dnaj protein
      was removed. Administration of radiolabelled mevalonic acid to cotyledons and
      isolation of glyoxysomes yielded labelled Dnaj protein which remained membrane
      bound during the purification of glyoxysomal membranes by floatation in a density
      gradient.

PMID- 8307023
TI  - Three-dimensional structure of (1-71)bacterioopsin solubilized in
      methanol/chloroform and SDS micelles determined by 15N-1H heteronuclear NMR
      spectroscopy.
AB  - Spatial structures of a chymotryptic fragment C2 (residues 1-71) of bacterioopsin
      from Halobacterium halobium, solubilized in a mixture of methanol/chloroform
      (1:1, by vol.) and 0.1 M 2HCO2NH4, or in perdeuterated sodium (2H)dodecyl sulfate
      (SDS) micelles in the presence of perdeuterated (2,2,2-2H)trifluoroethanol, were
      determined by two-dimensional and three-dimensional heteronuclear 15N-1H NMR
      techniques. The influence of (2,2,2-2H)trifluoroethanol on the conformational
      dynamics of C2 in micelles and the effect of the salt (organic mixture) were
      studied. Under the best conditions, 1H and 15N resonances of 15N-uniformly
      enriched protein were assigned in both milieus by homonuclear two-dimensional NOE
      (NOESY) and two-dimensional total-correlated (TOCSY) spectra and heteronuclear
      three-dimensional NOESY-multiple-quantum-correlation (HMQC) and TOCSY-HMQC
      spectra. 651 (organic mixture) and 520 (micelles) interproton-distance
      constraints, derived from volumes of cross-peaks in two-dimensional NOESY and
      three-dimensional NOESY-HMQC spectra, along with deuterium exchange rates of
      amide groups measured in both milieus and 51 HN-C alpha H coupling constants
      obtained in the case of the organic mixture, were used in the construction of C2
      spatial structures. Obtained structures are similar in both milieus and have two
      right-handed alpha-helical regions stretching from Pro8 to Met32 and Phe42 to
      Tyr64 (organic mixture), and from Pro8 to Met32 and Ala39 to Leu62 (micelles). In
      micelles, the second alpha helix is terminated by C-cap Gly63, adopting a
      conformation characteristic of a left-handed helix. Residues Gly65 to Thr67 from
      the turn of a right-handed helix. In the isotropic medium of the organic mixture,
      the C-terminal region of residues 65-71 lacks an ordered structure. Torsion
      angles chi 1 were unequivocally determined for 18 alpha-helical residues in both
      milieus. In the isotropic organic mixture and anisotropic micellar system, C2
      remains a compact structure with a characteristic size of 3.0-3.5 nm. C2 seems to
      be present in at least two conformational states, packed and unpacked. Using NMR
      data, along with the electron cryomicroscopy model of bacteriorhodopsin
      [Henderson, R., Baldwin, J. M., Ceska, T. A., Zemlin, F., Beckman, E. & Downing,
      K. H. (1990) J. Mol. Biol. 213, 899-929], we suggested a model for the
      conformation of C2 in this putative close-packed state. However, no NOE contact
      between alpha helices was found in either milieu.

PMID- 8307024
TI  - Magnetic-circular-dichroism studies of Escherichia coli cytochrome bo.
      Identification of high-spin ferric, low-spin ferric and ferryl [Fe(IV)] forms of
      heme o.
AB  - Room-temperature (295 K) magnetic-circular-dichroism spectra at 280-2500 nm have
      been recorded for Escherichia coli cytochrome bo in its fast form (which has a g
      = 3.7 EPR signal and reacts rapidly with cyanide) and for its formate, fluoride,
      cyanide and hydrogen-peroxide derivatives. The spectra of all forms are dominated
      by signals from low-spin ferric heme b. These include a porphyrin-to-ferric ion
      charge-transfer transition in the near-infrared region (the near-infrared charge
      transfer band) at 1610 nm. High-spin ferric heme o gives rise to a negative
      magnetic-circular-dichroism feature at 635, 642 and 625 nm (corresponding to a
      shoulder observed in the electronic absorption spectra) and a derivative charge
      transfer feature at 1100, 1180 and 940 nm for the fast, formate and fluoride
      forms, respectively. The energies of these bands confirm that fluoride and
      formate are ligands to heme o. The energies of the analogous bands in the
      spectrum of fast cytochrome bo are typical for high-spin ferric hemes with
      histidine and water axial ligands. Addition of cyanide ion to fast cytochrome bo
      causes a red shift in the position of the Soret absorption peak, from 406.5 nm to
      413 nm, and results in the loss of the 635-nm feature from the magnetic-circular
      dichroism spectrum and of the corresponding shoulder in the electronic absorption
      spectrum. In the magnetic-circular-dichroism spectrum, the intensities of the
      Soret and alpha, beta bands are significantly increased. New near-infrared charge
      transfer intensity is observed at 1000-2300 nm with a peak near 2050 nm. These
      changes are interpreted as resulting from a high-spin to low-spin transition at
      ferric heme o brought about by the binding of cyanide ion. The energy of the near
      infrared charge-transfer band suggests that the cyanide ion is bridged to the CuB
      of the binuclear site. Treatment of fast cytochrome bo with hydrogen peroxide
      also causes a red shift in the position of the Soret absorbance, to 412 nm, and a
      loss of the 625-nm absorption shoulder. Changes in the magnetic-circular
      dichroism spectrum at 450-600 nm are observed, but there is no significant
      increase in the intensity of the magnetic-circular-dichroism Soret band and no
      new near-infrared charge-transfer bands are detected, ruling out a similar high
      spin to low-spin transition at heme o.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8307025
TI  - Fluorescence resonance energy transfer within the regulatory light chain of
      myosin.
AB  - Rabbit skeletal muscle myosin regulatory light chain-2 (LC2) contains two
      reactive cysteine residues, Cys125 and Cys154, and one tryptophan at position
      137. Using wild-type rabbit LC2 or its genetically engineered mutant with Cys125-
      >Arg (C125R), these residues can be selectively modified with fluorescent or
      chromophoric probes for spectroscopic studies. We have bound suitable
      donor/acceptor probe pairs to the two cysteine residues and Trp137 in LC2 or
      C125R, and measured the distance in solution between the probes by fluorescence
      resonance energy transfer spectroscopy. C125R was made to facilitate specific
      labelling of the less reactive Cys154, thus allowing the distance between Cys154
      and Trp137 to be measured. Our measurements show that these residues are in close
      proximity to each other, the distance between them ranging from 1.7 nm (between
      Cys125 and Trp137) to 2.7 nm (Cys125 and Cys154). These results suggest that
      Cys125, Trp137 and Cys154, spanning up to 29 residues in the sequence of LC2, are
      spatially close, consistent with these residues residing within a C-terminal
      globular domain. The distances we obtained are in agreement with previous
      crosslinking studies [Huber, P. A., Brunner, U.T. & Schaub, M. C. (1989)
      Biochemistry 28, 9116-9123; Saraswat, L. & Lowey, S. (1991) J. Biol. Chem. 266,
      19777-19785] and structure predictions of LC2. LC2 is located at the head-rod
      junction of the myosin crossbridge, and provides the primary regulatory mechanism
      in molluscan and smooth muscle. In skeletal muscle, its functional role is
      unclear, although it has been implicated in modulating actomyosin interaction
      [Metzger, J. M. & Moss, R. L. (1992) Biophys. J. 63, 460-468]. The incorporation
      of spectroscopic probes onto the light chains of myosin in solution or in fibres
      has become a valuable tool for evaluating the dynamic properties of the
      crossbridge during force generation.

PMID- 8307026
TI  - 1H resonance assignments and secondary structure of the carbon monoxide complex
      of soybean leghemoglobin determined by homonuclear two-dimensional and three
      dimensional NMR spectroscopy.
AB  - Homonuclear two-dimensional and three-dimensional 1H-NMR spectroscopy has been
      utilized to study the 15.9-kDa protein soybean leghemoglobin. NMR experiments
      were performed on the diamagnetic carbon monoxide complex at two temperatures and
      two pH values. Sequence-specific assignments have been made for 94% of the
      backbone and approximately 70% of the expected side-chain resonances. The
      secondary structure of leghemoglobin in solution has been determined on the basis
      of NOE connectivity patterns, hydrogen exchange and chemical-shift analyses.
      Leghemoglobin consists of seven helices and, unlike mammalian myoglobins, is
      missing the D helix. Instead an extended loop, the CE loop, is observed which
      might have importance for ligand entry into and exit from the protein interior.
      The hydrogen exchange behavior for the F helix and at the beginning of the A
      helix suggests different dynamic stability compared to other helical regions in
      leghemoglobin. Population of a second protein conformation, in which there is
      perturbation at the A-G-H helix interface, is observed at low pH.

PMID- 8307027
TI  - Proteinase yscD (oligopeptidase yscD). Structure, function and relationship of
      the yeast enzyme with mammalian thimet oligopeptidase (metalloendopeptidase, EP
      24.15).
AB  - The yeast PRD1 gene, encoding proteinase yscD, was cloned by complementation of
      the prd1-6 point mutation. Sequencing of the gene revealed an open reading frame
      of 2.136 kb, encoding a protein of 712 amino acids with a calculated molecular
      mass of 81.8 kDa. The sequence HEGLG beginning at residue 501 represents the
      HEXXH motif, unique for the zinc metallo-peptidases. Sequence comparison revealed
      complete identity of the proteinase yscD gene with a recently published open
      reading frame of yeast chromosome III. We found 34.8% identity between proteinase
      yscD and rat metalloendopeptidase (thimet oligopeptidase, EP 24.15). Proteinase
      yscD hydrolyzes several chromogenic and fluorogenic peptides that are substrates
      of thimet oligopeptidase. N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p
      aminobenzoic acid, a compound designed as specific inhibitor of EP 24.15, is also
      a strong inhibitor of the yeast enzyme. Proteinase yscD is a nonvacuolar enzyme.
      3-5% of the total enzyme activity can be detected in the intermembrane space of
      mitochondria. In a mutant carrying a deletion of the PRD1 gene no proteinase yscD
      activity is detectable in the cytoplasm and in mitochondria of these cells. They
      do not show any grossly altered phenotype but exhibit a decrease in the
      intracellular degradation of peptides. This suggests a function of proteinase
      yscD in the late stages of protein degradation.

PMID- 8307028
TI  - The amino acid sequence of iguana (Iguana iguana) pancreatic ribonuclease.
AB  - The pyrimidine-specific ribonuclease superfamily constitutes a group of
      homologous proteins so far found only in higher vertebrates. Four separate
      families are found in mammals, which have resulted from gene duplications in
      mammalian ancestors. To learn more about the evolutionary history of this
      superfamily, the primary structure and other characteristics of the pancreatic
      enzyme from iguana (Iguana iguana), a herbivorous lizard species belonging to the
      reptiles, have been determined. The polypeptide chain consists of 119 amino acid
      residues. The positions of insertions and deletions in the sequence are identical
      to those in the enzyme from snapping turtle. However, the two enzymes differ at
      54% of the amino acid positions. Iguana ribonuclease contains no carbohydrate,
      although the enzyme possesses three recognition sites for carbohydrate
      attachment, and has a high number of acidic residues in a localized part of the
      sequence.

PMID- 8307029
TI  - Secretion, purification and characterization of a soluble form of the yeast KEX1
      encoded protein from insect-cell cultures.
AB  - The Saccharomyces cerevisiae KEX1 gene encodes a carboxypeptidase involved in the
      C-terminal processing of the lysine and arginine residues from the precursors of
      K1 and K2 killer toxins and alpha-factor (mating pheromone). In order to produce
      large quantities of this unique carboxypeptidase for structural studies, a
      functional soluble form was obtained by deleting 224 amino acids from the C
      terminus of the KEX1-encoded protein which includes a putative membrane-spanning
      domain. The resulting truncated KEX1 gene (KEX1 delta) has been expressed in the
      baculovirus/insect cell system. The protein (Kex1 delta p) is efficiently
      secreted into the culture medium and was purified to apparent homogeneity with a
      yield of approximately 4 mg/l culture. Kex1 delta p is a glycoprotein with a
      molecular mass of 56 kDa, its N-terminal sequence is identical to that of the
      full-length membrane-associated form of the enzyme [Latchinian-Sadek, L. &
      Thomas, D. Y. (1993) J. Biol. Chem. 268, 534-540], and like the full-length
      enzyme it is not made as a proenzyme. For the soluble enzyme form, the optimum pH
      for activity was 5.5-6.0, and the apparent pI value of the protein determined by
      isoelectric focusing was 4.2. The enzyme cleaves arginine from the C-terminus of
      the synthetic peptide benzoyl-Phe-Ala-Arg with Km 335 microM and Vmax 282
      mumol.min-1 x mg protein-1. Insect-cell-derived Kex1 delta p processes alpha
      factor-Lys-Arg, a known natural substrate, to mature active alpha-factor in a
      manner similar to the membrane-associated full-length enzyme. This secreted form
      of the enzyme is a convenient source for the isolation of substantial quantities
      of the pure enzyme for detailed kinetic and structural studies.

PMID- 8307030
TI  - Undecagold cluster modified tRNA(Phe) from Escherichia coli and its activity in
      the protein elongation cycle.
AB  - An undecagold cluster (Au11) of molecular mass 6200Da was attached to the 3-(3
      amino-3-carboxypropyl)uridine at position 47 of tRNA(Phe) from Escherichia coli.
      This modified tRNA can be enzymically aminoacylated with phenylalanine in the
      reaction catalyzed by phenylalanyl-tRNA synthetase. Au11-labeled Phe-tRNA(Phe)
      forms a ternary complex with the elongation factor Tu.GTP and is active in
      poly(U)-dependent poly(phe) synthesis. The Au11 modification does not hinder the
      specific binding of tRNA to distinct ribosomal binding sites or the precise
      positioning of the aminoacyl and peptidyl residues in the peptidyltransferase
      center, and does not impair the translocation. The modified tRNA is suitable for
      the identification of ribosomal binding sites by scanning transmission electron
      microscopy and for crystallographic studies of the 70S ribosome at different
      states of the protein-elongation cycle.

PMID- 8307031
TI  - 1H one-dimensional and two-dimensional NMR studies of the ferricytochrome c 551
      from Rhodocyclus gelatinosus.
AB  - 1H two-dimensional NMR spectroscopy has been applied to the oxidized form of
      cytochrome c 551 from Rhodocyclus gelatinosus, which is paramagnetic with S =
      1/2. The investigation has allowed a complete and unambiguous assignment of the
      heme protons and some residues around the heme. We have learned that: the
      conformation of the axial methionine is equal to that of horse heart cytochrome c
      and different from two isoenzymes of the same cytochrome c 551 from a different
      strain; pKa of 6.6 +/- 0.3 has been detected through the shift variations of
      seventh propionate protons. The detailed differences with other cytochromes c in
      the hyperfine shifts are discussed.

PMID- 8307032
TI  - The derivation of the formyl-group oxygen of chlorophyll b in higher plants from
      molecular oxygen. Achievement of high enrichment of the 7-formyl-group oxygen
      from 18O2 in greening maize leaves.
AB  - The mechanism of formation of the formyl group of chlorophyll b has long been
      obscure but, in this paper, the origin of the 7-formyl-group oxygen of
      chlorophyll b in higher plants was determined by greening etiolated maize leaves,
      excised from dark-grown plants, by illumination under white light in the presence
      of either H2(18)O or 18O2 and examining the newly synthesized chlorophylls by
      mass spectroscopy. To minimize the possible loss of 18O label from the 7-formyl
      substituent by reversible formation of chlorophyll b-7(1)-gem-diol (hydrate) with
      unlabelled water in the cell, the formyl group was reduced to a hydroxymethyl
      group during extraction with methanol containing NaBH4: chlorophyll a remained
      unchanged during this rapid reductive extraction process. Mass spectra of
      chlorophyll a and [7-hydroxymethyl]-chlorophyll b extracted from leaves greened
      in the presence of either H2(18)O or 18O2 revealed that 18O was incorporated only
      from molecular oxygen but into both chlorophylls: the mass spectra were
      consistent with molecular oxygen providing an oxygen atom not only for
      incorporation into the 7-formyl group of chlorophyll b but also for the well
      documented incorporation into the 13(1)-oxo group of both chlorophylls a and b
      [see Walker, C. J., Mansfield, K. E., Smith, K. M. & Castelfranco, P. A. (1989)
      Biochem. J. 257, 599-602]. The incorporation of isotope led to as much as 77%
      enrichment of the 13(1)-oxo group of chlorophyll a: assuming identical
      incorporation into the 13(1) oxygen of chlorophyll b, then enrichment of the 7
      formyl oxygen was as much as 93%. Isotope dilution by re-incorporation of
      photosynthetically produced oxygen from unlabelled water was negligible as shown
      by a greening experiment in the presence of 3-(3,4-dichlorophenyl)-1,1
      dimethylurea. The high enrichment using 18O2, and the absence of labelling by
      H2(18)O, unequivocally demonstrates that molecular oxygen is the sole precursor
      of the 7-formyl oxygen of chlorophyll b in higher plants and strongly suggests a
      single pathway for the formation of the chlorophyll b formyl group involving the
      participation of an oxygenase-type enzyme.

PMID- 8307033
TI  - Effect of acclimation temperature on the concentration of uncoupling protein and
      GDP binding in rat brown fat mitochondria.
AB  - The effect of the acclimation temperature on the concentration of the uncoupling
      protein (UCP) and specific GDP binding in rat brown adipose tissue mitochondria
      was investigated. UCP was measured by competition ELISA using purified UCP as a
      standard and antiserum developed against the C-terminus of the protein. UCP was
      purified by means of specific polyclonal antibodies immobilized on protein-A-
      agarose. It represented 2.4% of the total protein in brown fat mitochondria from
      rats acclimated to 4 degrees C and 1.1% in mitochondria from rats acclimated to
      29 degrees C. No UCP was found in liver mitochondria. The molar ratio of bound
      GDP and UCP was 0.5 in mitochondria from warm-acclimated rats and 1.0 in cold
      acclimated rats. The GDP/UCP ratio was increased from 0.5 to 1.0 after a 90-min
      exposure to 4 degrees of warm-acclimated rats; it was decreased from 1.0 to 0.5,
      when cold-acclimated rats were transferred to 29 degrees C for 2 4h. Treatment of
      mitochondrial membranes from warm-acclimated rats with 3 M urea at pH 10.0
      increased the GDP/UCP ratio from 0.5 to 1.0. Specific GDP binding was a direct
      measure of the UCP concentration during maximally activated or inactivated
      thermogenesis in brown adipose tissue. We suggest that variable GDP binding
      reflects the functional activity of UCP based on different protein conformations.

PMID- 8307034
TI  - Two binding sites of inhibitors in NADH: ubiquinone oxidoreductase (complex I).
      Relationship of one site with the ubiquinone-binding site of bacterial
      glucose:ubiquinone oxidoreductase.
AB  - The effect of ten naturally occurring and two synthetic inhibitors of
      NADH:ubiquinone oxidoreductase (complex I) of bovine heart, Neurospora crassa and
      Escherichia coli and glucose:ubiquinone oxidoreductase (glucose dehydrogenase) of
      Gluconobacter oxidans was investigated. These inhibitors could be divided into
      two classes with regard to their specificity and mode of action. Class I
      inhibitors, including the naturally occurring piericidin A, annonin VI,
      phenalamid A2, aurachins A and B, thiangazole and the synthetic fenpyroximate,
      inhibit complex I from all three species in a partially competitive manner and
      glucose dehydrogenase in a competitive manner, both with regard to ubiquinone.
      Class II inhibitors including the naturally occurring rotenone, phenoxan,
      aureothin and the synthetic benzimidazole inhibit complex I from all species in
      an non-competitive manner, but have no effect on the glucose dehydrogenase.
      Myxalamid PI could not be classified as above because it inhibits only the
      mitochondrial complex I and in a competitive manner. All inhibitors affect the
      electron-transfer step from the high-potential iron-sulphur cluster to
      ubiquinone. Class I inhibitors appear to act directly at the ubiquinone-catalytic
      site which is related in complex I and glucose dehydrogenase.

PMID- 8307036
TI  - Secondary structure and signal assignments of human-immunodeficiency-virus-1
      protease complexed to a novel, structure-based inhibitor.
AB  - We report comprehensive NMR studies in solution of the human-immunodeficiency
      virus (HIV)-1 protease. Stable solutions of the protease were obtained by
      complexing the protein to a designed cyclic urea inhibitor DMP 323. A variety of
      triple-resonance experiments provided essentially complete 1H, 13C and 15N NMR
      signal assignments of the protease. These assignments, together with short-range
      NOE constraints, coupling constants and hydrogen-exchange data, yielded the
      secondary structure of the protease in solution. The results reported herein open
      the way to the determination of the high-resolution three-dimensional solution
      structures of protease/inhibitor complexes, as well as to studies of protease
      dynamics and solvent interactions.

PMID- 8307035
TI  - The mode of action of SA-FF22, a lantibiotic isolated from Streptococcus pyogenes
      strain FF22.
AB  - SA-FF22 is a lanthionine-containing bacteriocidal peptide isolated from
      Streptococcus pyogenes strain FF22. The peptide interacts closely with non
      energised artificial phospholipid vesicles, as evidenced by a 'blue shift' in the
      fluorescent emissions associated with a tryptophan residue within the peptide
      sequence. Furthermore, SA-FF22 induced efflux of radiolabelled amino acids from
      artificially energised cytoplasmic membrane vesicles and arrested uptake of amino
      acids by intact cells. By measuring the decrease in membrane potential of both
      starved and energised SA-FF22-treated cells, and through the use of artificial
      planar membranes, a potential of approximately 100 mV was deduced as the minimum
      required to induce pore formation by SA-FF22. This threshold potential is
      independent of the orientation of the applied voltage (i.e. trans or cis
      orientations are equally effective). Single channel conductance measurements
      suggested that the pores formed by SA-FF22 are relatively unstable, short-lived
      and approximately 0.5-0.6 nm in diameter. This is somewhat smaller than those of
      the previously described, pore-forming lantibiotics and should not allow
      significant efflux of large molecules such as ATP. Thus, death of affected cells
      seems to result from membrane-potential disruption and subsequent exhaustion of
      the cells.

PMID- 8307037
TI  - Genuine and apparent cross-reaction of polyclonal antibodies to proteins and
      peptides.
AB  - Antiserum to a native protein may cross-react with the corresponding denatured
      protein or with peptides. The cross-reaction is either a genuine property of the
      antibodies or caused by antibodies produced against some unfolded protein
      contaminating the native protein used for immunization. Appropriate conformation
      sensitive immunoassays must be employed to distinguish a genuine from an apparent
      cross-reaction. In the present study, we have analyzed critically the cross
      reaction of rabbit antisera against proteins and peptides. We have distinguished
      between genuine and apparent cross-reaction with the help of the protein A
      antibody-capture ELISA, a new conformation-sensitive ELISA format. Three systems
      were analyzed: cross-reaction of antisera to native yeast and horse cytochrome c
      with unfolded apo-cytochrome c; cross-reaction of antisera to a coiled-coil
      leucine-zipper peptide with a homologous random-coil peptide obtained by
      introducing two proline residues into the leucine-zipper sequence; cross-reaction
      of antisera to two peptides that correspond to the N-terminal and an internal
      sequence of ferredoxin: NADP+ reductase (FNR), with the native enzyme. The
      reaction of the anti-(cytochrome c) sera was clearly due to antibodies produced
      against unfolded protein, it was an apparent and not a genuine cross-reaction.
      Furthermore, the apparently cross-reactive antibodies to horse cytochrome c did
      not discriminate against sequence-related proteins from dog, beef, rabbit and
      pigeon. In contrast, antibodies to the leucine-zipper peptide did cross-react in
      a genuine way with the homologous random-coil peptide, that is, the cross
      reactive antibodies do not seem to have been produced against the unfolded form
      of the leucine-zipper peptide. Of the two anti-peptide sera the one against the
      unstructured and highly accessible N-terminal segment reacted strongly with the
      native protein. The second serum against a solvent-accessible turn-like sequence
      of FNR showed apparent cross-reactivity: antibodies recognizing the native
      protein were directed against a minor conformational isoform of the free peptide
      and did not react with the principal form(s) of the free peptide. The generation
      of cross-reactive antibodies depends on the conformational stability and
      integrity of the immunogen and on the molecular form of its application, i.e.,
      free, polymerized or carrier-bound. The results clarify the different nature of
      cross-reactivity of antisera to proteins and peptides. This knowledge is crucial
      if antisera are to be used as conformation-specific probes.

PMID- 8307038
TI  - Cloning and expression of three abrin A-chains and their mutants derived by site
      specific mutagenesis in Escherichia coli.
AB  - DNAs encoding of three abrin A-chains were obtained from the cDNA library of
      Abrus precatorius by polymerase chain reaction and ligated into the expression
      vector, pGEX-2T. The mature A-chains of abrins a, b and d have been expressed in
      the cytoplasm of Escherichia coli, and the yield of the soluble recombinant
      proteins was 7 mg/l induced culture. Three recombinant abrin A-chains were
      purified to be homogeneity and their N-glycosidase ability to inhibit protein
      biosynthesis in a cell-free system and to depurinate 28S rRNA in rat liver
      ribosomes was demonstrated in vitro. The recombinant abrin-a A-chain had the
      highest N-glycosidase activity among three recombinant abrin A-chains while the
      recombinant abrin-b A-chain, the least. Three mutants, glutamic-acid-to-alanine
      replacement (E164A), arginine to leucine (R167L) or double mutation (E164A and
      R167L) were constructed and expressed. The protein-biosynthesis-inhibitory
      activity of mutant (E164A), mutant (R167L) and the double mutant was found to be
      25-fold, 625-fold and 1250-fold lower than that of wild type, respectively. The
      results indicated that Arg167 was essential for abrin toxin A-chain catalysis.

PMID- 8307039
TI  - Solution structure of the variant-3 neurotoxin from Centruroides sculpturatus
      Ewing.
AB  - The solution structure of the CsE-v3 neurotoxin from the venom of the North
      American scorpion Centruroides sculpturatus Ewing (CsE) has been determined by a
      hybrid refinement procedure that employed distance geometry and dynamical
      simulated annealing. Distance constraints deduced from the nuclear Overhauser
      effect spectroscopy data and torsion angle constraints deduced from the vicinal
      coupling constant data were used in the refinement procedure. A family of
      simulated annealing structures that showed no constraint violations was
      generated. The energy-minimized average structure exhibited root-mean-square
      deviations of 0.121 nm for the backbone and 0.182 nm for all atoms, with respect
      to this family. These studies confirm the previously qualitative NMR findings
      about the secondary structural features, viz. the presence of a short alpha-helix
      composed of residues 23-31 and an antiparallel beta-sheet composed of the strands
      of residues 1-5, 45-50 and 36-42. A cluster of aromatic ring systems is located
      on one side of the protein. The solution and crystal structures have similar
      overall features, but show some minor differences.

PMID- 8307040
TI  - Solution structure of synthetic peptides corresponding to the C-terminal helix of
      interleukin-6.
AB  - Two synthetic peptides corresponding to the C-terminal 19 residues of human and
      murine interleukin-6, respectively, have been synthesized and their structures in
      solution investigated using high-resolution 1H-NMR spectroscopy. Both peptides
      show a marked dependence of chemical-shift dispersion on pH, with a greater
      degree of structure apparent above pH 4.5, where their glutamate carboxyl groups
      are ionised. In purely aqueous solution, neither peptide adopts a well-defined
      structure, although the murine peptide has characteristics of a nascent helix.
      Titration of the murine peptide with trifluoroethanol produced a significant
      increase in structure, which was then investigated using two-dimensional NMR. In
      50% (by vol.) trifluoroethanol the murine peptide consists of a well-defined
      central helix of 12 residues with unstructured N-terminal and C-terminal regions.
      These observations lend experimental support to the current model of the
      interleukin-6 structure, which proposes a four-helical bundle with the last helix
      encompassing the C-terminal 20-30 residues. Furthermore, the fact that synthetic
      peptides corresponding to part of the putative receptor-binding surface of
      interleukin-6 are able to adopt a similar conformation in solution to that
      proposed for the intact protein suggests that such peptide analogues should be
      useful starting points in the design of peptide agonists and antagonists of
      interleukin-6.

PMID- 8307041
TI  - Detection in an enzyme immunoassay of an immune response to a recombinant
      fragment of the 128 kilodalton protein (CagA) of Helicobacter pylori.
AB  - The possibility of using a recombinant fragment of the CagA (128 kDa protein) for
      the diagnosis of Helicobacter pylori infection was evaluated. Following cloning
      of the gene coding for the CagA, a recombinant fragment of it was expressed in
      Escherichia coli, purified and used in Western blot and an EIA to screen sera
      from 82 patients with gastroduodenal disease who underwent endoscopic
      examination. In Western blot, good correlation was found between the serological
      data obtained with the recombinant antigen and those obtained using non-purified
      extracts of Helicobacter pylori. The EIA using the antigen showed a sensitivity
      of 96.2% and a specificity of 96.6% compared with Western blot. These data
      indicate that the recombinant protein is a reliable antigen for detection of
      infections with Helicobacter pylori strains that are associated with disease. The
      EIA assay described may be used in follow-up of the progression of the illness
      and the results of therapy.

PMID- 8307042
TI  - Detection of Chlamydia trachomatis in the urine of young Norwegian males by
      enzyme immunoassay.
AB  - First-void urine samples from 392 Norwegian military conscripts were investigated
      for the presence of Chlamydia trachomatis by enzyme immunoassay (EIA) on day 1
      and day 5 after collection. Positive samples were subsequently investigated by
      direct immunofluorescence (IF) microscopy for the presence of chlamydial
      elementary bodies (EBs) in the urine pellet, and urethral swab material taken
      from the EIA-positive individuals was cultured. 4.8% (19/392) of the urine
      samples were EIA-positive on day 1, and 5.4% (21/392) were positive on day 5,
      with a combined total of 6.6% (26/392). Twenty-four of the 26 urine samples were
      confirmed as positive on IF microscopy. Urethral swabs were taken from 21 EIA
      positive individuals. Six of the swabs were positive on cell culture, whereas
      nine were positive on IF microscopy of swab material, suggesting that these
      techniques perform better in symptomatic cases than in male Chlamydia trachomatis
      carriers. In the urine samples a notable discrepancy in EIA results was seen when
      the same refrigerated samples were retested on day 5 compared to day 1. This
      discrepancy was probably due to storage-related factors.

PMID- 8307043
TI  - Evaluation of penicillin G in the prevention of streptococcal septicaemia in
      patients with acute myeloid leukaemia undergoing cytotoxic chemotherapy.
AB  - The efficacy of penicillin G was evaluated in the prevention of infections caused
      by streptococci in patients receiving remission induction or intensive
      consolidation treatment for acute myeloid leukaemia. Between 1980 and 1988, 29
      episodes of streptococcal septicaemia occurred in 139 treatment events. All
      patients received as prophylaxis regimen ciprofloxacin (n = 38) or a combination
      of polymyxin B with nalidixic acid (n = 42) or neomycin (n = 59). Six patients
      died of streptococcal septicaemia despite adequate antibiotic treatment. The high
      incidence of streptococcal septicaemia lead to the administration of penicillin G
      in addition to ciprofloxacin as prophylaxis regimen during the 14 days
      immediately following cytotoxic chemotherapy. Only two episodes of streptococcal
      septicaemia were documented after addition of penicillin G to the prophylaxis
      regimen (n = 76, p < 0.001). Both patients had an uneventful recovery after
      treatment with vancomycin. Patients receiving penicillin G prophylaxis
      experienced fever during 17% of the time and received antimicrobial therapy
      during 20% of the time per treatment event compared with 27% and 32% respectively
      of this time in patients receiving no streptococcal prophylaxis (p < 0.001).
      Penicillin G prophylaxis was associated with an increased incidence of fever of
      unknown origin and more frequent isolation of aerobic gram-negative bacteria in
      surveillance cultures. Penicillin G in combination with ciprofloxacin proved to
      be highly successful in preventing infections caused by streptococci and in
      reducing infection-related mortality and morbidity.

PMID- 8307044
TI  - Evaluation of serological methods in the diagnosis of Chlamydia pneumoniae
      pneumonia during an epidemic in Finland.
AB  - A complement fixation (CF) test, a micro-immunofluorescence (micro-IF) test and
      an enzyme immunoassay (EIA) using Re-lipopolysaccharide as antigen were compared
      in the diagnosis of chlamydial infection in 136 mainly elderly patients
      hospitalized with community-acquired pneumonia during a Chlamydia pneumoniae
      epidemic in Finland in 1986-1987. Chlamydial pneumonia was diagnosed in 58
      (42.6%) of the 136 pneumonia patients; 44 (75.9%) of them could be shown by micro
      IF to be caused by Chlamydia pneumoniae, three by Chlamydia psittaci and four by
      Chlamydia spp. Only 5 (11.4%) of 44 patients with Chlamydia pneumoniae pneumonia
      were IgM-positive, indicating that the majority of cases were reinfections. In
      this population of mainly elderly patients the CF test was insensitive, being
      positive in only 6 (10.3%) of 58 cases of chlamydial pneumonia. The EIA detected
      72.4% of cases and micro-IF 87.9% of cases (including infections with Chlamydia
      pneumoniae, Chlamydia psittaci and Chlamydia spp.). In the EIA 77% of positive
      cases were positive in serum samples taken a week apart, whereas the
      corresponding figure for micro-IF was 50%. In micro-IF the measurement of IgA
      antibody levels is recommended and IgM-positive sera should be retested after
      removal of IgG antibody to avoid false-positive findings due to presence of
      rheumatoid factor. The collection of a third serum sample, for instance one month
      after onset, is also recommended, since half of the patients showed a diagnostic
      response in the micro-IF only in the sera taken one month apart.

PMID- 8307045
TI  - Susceptibility to antimicrobial agents of Pseudomonas aeruginosa attached to
      siliconized latex urinary catheters.
AB  - The effect of siliconized latex urinary catheters on the in vitro activity of
      amikacin, ceftazidime, ciprofloxacin, norfloxacin and meropenem against
      Pseudomonas aeruginosa was determined by a microdilution assay. MICs of amikacin
      and meropenem increased at least 4-fold and 16-fold respectively in the presence
      of catheter material. The effect of catheter material on meropenem activity was
      not strain dependent and was similar for different brands of catheters. The
      susceptibility to antimicrobial agents of Pseudomonas aeruginosa attached to
      catheters for 6 and 24 hours was also evaluated. When bacteria attached for 6
      hours were used as inoculum, MBCs increased at least 8-fold for amikacin, 64-fold
      for ceftazidime, 64-fold for ciprofloxacin, 32-fold for norfloxacin and 2048-fold
      for meropenem. Similar results were observed when bacteria attached to catheters
      for 24 hours were used as inoculum. It is concluded that catheter material itself
      affected the in vitro activity of meropenem, and that the bactericidal activity
      of all antimicrobial agents against Pseudomonas aeruginosa present in biofilms on
      the surface of siliconized latex urinary catheters decreased dramatically, this
      effect being more pronounced with meropenem.

PMID- 8307047
TI  - Non-tropical pyomyositis in adults: report of four cases and literature review.
AB  - Four cases of non-tropical pyomyositis in adults are presented and 72 cases
      reported in the literature are reviewed. The diagnosis is often overlooked or
      delayed because most physicians are not familiar with the entity. Local signs of
      inflammation fever, leukocytosis and an elevated erythrocyte sedimentation rate
      are common features. Staphylococcus aureus is the most common pathogen and the
      thigh muscles are the most common site involved. Computerized tomography is used
      to establish the diagnosis and surgical incision and drainage in combination with
      antibiotic therapy is successful in the majority of the cases.

PMID- 8307046
TI  - Ceftriaxone versus penicillin G in the short-term treatment of meningococcal
      meningitis in adults.
AB  - Short-term treatment with ceftriaxone 2 g once daily for two days (group 1) was
      compared to treatment with a standard regimen of penicillin G (group 2) for six
      days in adults with meningococcal meningitis. Thirty-six patients were allocated
      in a randomized fashion to a treatment group: 16 to group 1 and 20 to group 2.
      The clinical and microbiological results were comparable in the two treatment
      groups. In both groups cultures of cerebrospinal fluid were sterile after 24
      hours. One patient in each group died. In group 1 one case of fulminant
      meningococcemia and one case of brain abscess required further antibiotic
      treatment. It is concluded that short-term treatment with ceftriaxone is feasible
      but patients with severe forms of meningitis would not be eligible for treatment
      with this regimen, and careful follow-up of the patients receiving ceftriaxone is
      necessary.

PMID- 8307048
TI  - Use of an immunoglobulin M containing preparation for treatment of two
      hypogammaglobulinemic patients with persistent Campylobacter jejuni infection.
AB  - This report describes two hypogammaglobulinemic patients with persistent
      Campylobacter jejuni infections in spite of IgG substitution and antibiotic
      therapy. Since serum bactericidal activity (SBA) depends on IgM, these patients
      were each treated with six doses of an IgM-containing immunoglobulin preparation
      (Pentaglobin) at three-week intervals. During IgG therapy SBA was not seen in
      either patient. However, one hour following administration of the IgM
      preparation, SBA increased to 90%. Just before the next dose SBA was still at the
      30-70% level. Both patients tolerated the therapy very well and there were no
      culture-confirmed relapses of Campylobacter jejuni infection. The IgM preparation
      may therefore be a useful alternative to conventional IgG in the treatment of
      hypogammaglobulinemic patients with persistent Campylobacter jejuni infection.

PMID- 8307049
TI  - Coxiella burnetii infection among subjects infected with HIV type 1 in the
      Central African Republic.
AB  - Sixty-six sera from HIV-1-seropositive adult African subjects and 49 sera from
      HIV-seronegative age and sex matched healthy African controls living in Bangui,
      Central African Republic, were screened for Coxiella burnetii antibody by an
      indirect immunofluorescent antibody test. 16.7% of HIV-infected patients and
      16.3% of the HIV-negative controls had positive IgG titres, with no significant
      difference between the two groups. Two of the seven HIV-infected patients
      seropositive for Coxiella burnetii for whom clinical data was available had a
      medical history compatible with symptomatic Q fever. These findings indicate that
      there is a high degree of exposure to Coxiella burnetii infection in Bangui. In
      individuals co-infected with HIV and Coxiella burnetii, cellular
      immunosuppression could favour symptomatic Q fever. Physicians should be aware of
      the possibility of symptomatic Coxiella burnetii infection among HIV-infected
      people, particularly in endemic regions for both infections such as in sub
      saharan Africa.

PMID- 8307051
TI  - Effect of inoculum size on antimicrobial susceptibility of Helicobacter pylori.
AB  - An agar dilution assay was used to assess the effect of inoculum size and culture
      period on the susceptibility of 15 clinical isolates of Helicobacter pylori to
      ampicillin, erythromycin, tetracycline, chloramphenicol, metronidazole and
      tinidazole. The mean MIC of the isolates increased 2.2- to 21.2-fold as the
      inoculum size progressed from 10(3) to 10(7) cfu/spot. Identical results were
      noted when isolates were maintained for two or four days prior to testing.
      Inoculum size should be carefully controlled when assessing the in vitro
      susceptibility of Helicobacter pylori.

PMID- 8307050
TI  - Antibody response to a two-dose influenza vaccine regimen in adult lymphoma
      patients on chemotherapy.
AB  - A study was conducted to determine if a two-dose regimen of influenza vaccine
      would enhance the immunologic response of 41 patients with lymphoma receiving
      chemotherapy. Hemagglutinin-inhibiting antibody responses to influenza A/H1N1,
      A/H3N2 and B virus occurred in 32%, 24% and 20% of patients following one dose,
      and in 49%, 41% and 46% of patients following two doses, respectively. Responses
      to one or more vaccine components occurred in 42% of patients after one dose and
      in 71% after two doses. Fifty percent of the patients who did not respond after
      one dose responded after two doses. A two-dose regimen of influenza immunization
      may significantly enhance the response rate of cancer patients receiving
      chemotherapy.

PMID- 8307052
TI  - Atypical bilateral symmetric erosive chronic polyarthritis in the course of Lyme
      disease.

PMID- 8307053
TI  - Native valve endocarditis caused by Staphylococcus capitis.

PMID- 8307055
TI  - Disseminated histoplasmosis in an AIDS patient in Spain.

PMID- 8307054
TI  - A case of fatal septicemia due to Mycobacterium kansasii.

PMID- 8307056
TI  - Use of the arbitrary primer polymerase chain reaction for investigating an
      outbreak of Clostridium difficile-associated diarrhea in AIDS patients.

PMID- 8307057
TI  - Prevalence of immunoglobulin G antibodies to Helicobacter pylori in Chilean
      individuals.

PMID- 8307058
TI  - Infections due to Flavimonas oryzihabitans: case report and literature review.

PMID- 8307059
TI  - Multiple sclerosis: new therapeutic concepts or better use of old drugs?

PMID- 8307060
TI  - Staging of Alzheimer-related cortical destruction.
AB  - The gradual intraneuronal accumulation of an insoluble fibrous material which
      partly consists of abnormally phosphorylated tau protein (neurofibrillary change)
      represents an important neuropathological hallmark of Alzheimer's disease.
      Neurofibrillary tangles and neuropil threads formed from this material develop in
      only a few types of cortical pyramidal cells. The first changes are seen in the
      entorhinal cortex. The destructive process then spreads into the hippocampal
      formation and eventually encroaches upon the isocortex. This sequence of events
      permits the distinction of six stages with a progressive increase in the severity
      of cortical destruction. The entorhinal region serves as an important interface
      between the isocortex and hippocampus. This interface function is markedly
      impaired due to the early deterioration of the entorhinal cortex. Severe
      entorhinal involvement is considered to represent the morphological counterpart
      of clinically incipient Alzheimer's disease. Similar changes are found in
      mentally impaired individuals suffering from Parkinson's disease or progressive
      supranuclear palsy.

PMID- 8307061
TI  - Pure progressive autonomic failure: a clinicopathological study.
AB  - Two cases of pure progressive autonomic failure (PAF) are presented. A postmortem
      study of one case (case 2) showed a pathology resembling that of Parkinson's
      disease. Marked cell loss was noted in the substantia nigra, nucleus ceruleus,
      and intermediolateral column of the spinal cord, while cell loss in the
      sympathetic ganglion was not remarkable. This case may be an exceptionally rare
      case of late-onset PAF in which autonomic failure was mainly ascribed to
      preganglionic (and central) pathology, although autonomic function tests
      suggested postganglionic sympathetic disorder in both cases.

PMID- 8307062
TI  - The association of meningioma and pituitary adenoma: report of seven cases and
      review of the literature.
AB  - Seven patients with the co-occurrence of meningioma and pituitary adenoma are
      reported. Diagnosis was based on histological examination and if not available on
      MR imaging. Extensive review of the literature reveals only 18 other cases with
      this association if meningiomas appearing after radiation therapy for pituitary
      tumors are excluded. As in isolated meningiomas, the female-to-male ratio is
      high. A preponderance of perisellar meningiomas is apparent. Another distinct
      characteristic of this combination is not revealed, since no specific typing of
      the meningioma and no specific endocrine syndrome is uncovered. Two patients
      presented with multiple meningiomas, of which one showed two histologically
      different tumor types. The presence of other tumors in association with pituitary
      adenomas and meningiomas in our series is striking and could suggest a genetic
      dysregulation leading to the development of these tumors.

PMID- 8307063
TI  - Muscle mitochondria investigation in myotonic dystrophy.
AB  - Mitochondrial abnormalities have been previously reported in some patients with
      myotonic dystrophy (DM). The aim of the present paper was to study muscle
      mitochondria in 32 DM patients by morphological, biochemical (when suggested by
      morphology) and genetic analysis. A single ragged red fiber, but no cytochrome c
      oxidase-negative fibers were found in the muscle specimen of 1 patient. However,
      mitochondrial enzyme activities resulted within the normal range. An electron
      microscopy study showed no significant mitochondrial changes. Southern blot
      analysis did not reveal any mitochondrial DNA heteroplasmy in all 32 patients. An
      explanation for the discordant results between this study and some previous
      reports of mitochondrial alterations in DM might be that their occasional
      presence is not related to the disease but to ageing. Another possibility is that
      among patients with a myotonic dystrophy phenotype, a small subgroup of subjects
      with a mitochondrial disease may exist and be differentiated.

PMID- 8307064
TI  - Evoked potentials in the evaluation of patients with mitochondrial myopathy.
AB  - Multimodality evoked potentials and pattern electroretinograms (PERGs) were
      performed in seventeen patients with histologically defined mitochondrial
      myopathy (MM). Brainstem auditory evoked potentials showed abnormalities in 47%
      and somatosensory evoked potentials in 76%. Visual evoked potentials were outside
      the normal range in 71%; PERGs exhibited a decreased amplitude or delayed P50 in
      78%. These findings may be considered as an expression of impairment of the
      central nervous system in MM, even if the specific mechanism, 'structural' or
      'functional', needs further investigation.

PMID- 8307065
TI  - Cognitive function in myotonic dystrophy: a follow-up study.
AB  - Intellectual and cognitive function were studied in 35 patients with myotonic
      dystrophy (DM). All 5 patients with the congenital form showed moderate or mild
      mental retardation. The 30 adult-onset patients had normal intelligence and
      memory quotients. In this adult-onset group no differences in cognitive function
      were observed either with respect to sex or physical disability. The sex of the
      affected parent, mother vs. father, was also without effect in this group. A
      follow-up study was performed in 16 patients with a mean test interval of 12
      years. There was no severe cognitive impairment over this time span or a
      significant correlation between the progression of physical and cognitive
      dysfunction.

PMID- 8307066
TI  - Leukocyte and platelet aggregation in patients with ischemic stroke: a case
      control study.
AB  - We evaluated simultaneously leukocyte and platelet aggregation in 40 untreated
      patients soon after atherothrombotic stroke and in 40 healthy controls matched
      for age, sex and risk factors. Both leukocyte and platelet aggregation were
      significantly increased in patients relative to controls (p < 0.01 and p < 0.02,
      respectively). However, whereas leukocyte aggregation was positive in a
      significantly higher proportion of patients with subsequent major neurological
      deficit compared to those with minor deficit (71% vs. 19%; p = 0.04), platelet
      aggregation was similar in the two patient groups. These data suggest different
      patterns of activation of leukocyte and platelet aggregation in patients with
      ischemic stroke. This finding may have pathophysiological and clinical
      implications.

PMID- 8307067
TI  - Immunosuppressive treatment in lower motor neuron syndrome with autoantibodies
      against GM1 ganglioside.
AB  - We report the results of immunosuppressive treatment with intravenous
      cyclophosphamide in 12 patients with lower motor neuron syndrome and elevated
      titers of serum autoantibodies to GM1 ganglioside. All patients had lower motor
      neuron dysfunction including proximal or distal weakness, fasciculation and
      muscle atrophy, but no upper motor neuron dysfunction such as hyperreflexia,
      spasticity or Babinski's sign. Electrophysiological studies revealed no evidence
      of conduction block, but EMG findings of acute or chronic denervation in the
      limbs were present. Serum biochemistry and immunological studies were negative
      for M protein. After a 6-month follow-up, despite a fall in antibody titer, there
      was no significant clinical improvement in any of the patients.

PMID- 8307068
TI  - Congenital muscular dystrophy associated with familial junctional epidermolysis
      bullosa letalis.
AB  - A 20-year-old patient was born with epidermolysis bullosa and a severe, slowly
      progressive muscle disease. Skin biopsy demonstrated junctional epidermolysis
      bullosa. Muscle biopsy demonstrated degenerative changes with increase in
      connective tissue, fibre size variability, rods and cytoplasmic bodies, central
      nuclei. In muscle biopsy dystrophin, chondroitin unsulphate, chondroitin 4
      sulphate, chondroitin 6-sulphate, heparan sulphate, collagen III, collagen IV and
      VI, laminin, and fibronectin were normally distributed. This is the first report
      of the association of a form of congenital muscular dystrophy with junctional
      epidermolysis bullosa and, together with the previous reports of muscle
      involvement in epidermolysis bullosa simplex and dystrophica, it suggests the
      existence of a syndrome characterized by the contemporaneous presence of skin and
      muscle involvement.

PMID- 8307069
TI  - Early hypoperfusion of technetium-99m hexamethylprophylene amine oxime brain
      single photon emission computed tomography in a patient with carbon monoxide
      poisoning.
AB  - Single photon emission computed tomography (SPECT) with technetium-99m (99mTc)
      hexamethylprophylene amine oxime (HM-PAO) were repeatedly performed in a 55-year
      old woman with carbon monoxide (CO) poisoning. The initial brain SPECT 10 days
      after anoxic insult showed focal hypoperfusion which appeared 20 days prior to
      the onset of delayed neurologic sequelae, and the findings of follow-up SPECTs
      correlated with the clinical course of CO poisoning. The possibilities of early
      hypoperfusion on SPECT of acute CO poisoning were discussed.

PMID- 8307070
TI  - Advances in laparoscopic renal and ureteral surgery.
AB  - With the introduction of laparoscopy into adult urology, a vast new field has
      suddenly opened itself up to the urologic surgeon, filled with exciting and
      promising possibilities of applying the principles of minimally invasive surgery
      to an ever increasing number of diseases that so far have only been approachable
      by incisional surgery. While undoubtedly, laparoscopy has been providing
      unprecedented challenges to the principles of open surgery, it is of paramount
      importance to critically evaluate each new laparoscopic procedure against its
      open surgical counterpart. However, despite a widely publicized higher
      complication rate for laparoscopic procedures, it must not be overlooked that
      each laparoscopist must go through his/her very own individual learning curve;
      although a painful process at times, it is not any different than the novice's
      introduction to open incisional surgery. The problems of the learning curve can
      be partly alleviated by carefully studying the basic principles of laparoscopy in
      the animal laboratory, and by subsequent clinical training under the guidance of
      an experienced laparoscopist. The discoverer's enthusiasm for his or her own
      newly developed procedure and the instinctive negative reaction of the practicing
      community to new concepts that threaten to overturn what is perceived as 'tried
      and true', must both be tempered by the accumulation of clinical data, testing
      the validity of all procedures, new and old alike. To this end, surgeons have the
      opportunity to explore a gentler form of surgical practice, one in which the
      practitioner can heal without the need to harm.

PMID- 8307071
TI  - Undiversion after previous cystectomy and Bricker derivation.
AB  - A 45-year-old man operated in 1989 for bladder cancer by a Bricker diversion was
      suffering from intractable eczema and stoma problems. A undiversion was
      unavoidable. A 'Camey type' diversion having been performed, a simple ligation of
      the membranoprostatic urethra seemed impossible but was in fact surprisingly
      easy. After introduction of a Benique sound, a simple opening in a kind of
      diaphragm at the proximal end of the ligated urethra made it possible to
      anastomose the created pouch. The patient remained continent during day- and
      nighttime.

PMID- 8307072
TI  - Significance of full nocturnal erections with short duration.
AB  - The aim of the study was to clarify the pathophysiologic significance of full but
      short-lived nocturnal erections observed in some impotent men. Penile circulation
      was assessed by color Doppler sonography and pharmacocavernosometry in 35
      impotent patients who underwent polysomnographic recording of nocturnal
      erections. In each case, there were at least 3 erectile episodes with a complete
      rigidity (always > 700 g) but with a short duration (mean duration of the maximum
      level of full erection = 4 min; always < 6 min). All patients demonstrated a
      normal arterial inflow with mean +/- SEM right and left cavernosal peak flow
      velocities of 39.5 +/- 1.8 and 41.3 +/- 1.5 cm/s, respectively.
      Pharmacocavernosometry detected a dysfunction of the cavernous veno-occlusive
      mechanism (mean +/- SEM maintenance flow: 45 +/- 8 ml/min and mean +/- SEM
      corporal pressure decay over 30 s: 82.5 +/- 9 mm Hg) in 18 patients (51%). In
      these patients, this finding may be a possible explanation for the short duration
      of nocturnal erectile episodes. In the remaining 17 patients (49%) with normal
      penile vascular status, a dysfunction of the adrenergic system could play a role
      in the pathophysiology of this picture. Full but short-lived nocturnal erections,
      as assessed by polysomnographic recording, are indicative of a normal arterial
      status and should encourage further assessment of the corporal veno-occlusive
      mechanism.

PMID- 8307073
TI  - Deep dorsal vein arterialization in vascular impotence.
AB  - 33 patients underwent a penile deep dorsal vein arterialization (DDVA) (11 venous
      leak, 8 pure arteriogenic impotence, 14 mixed arterial and venous impotence). The
      mean follow-up was 12 months. Surgery was considered successful when the patients
      had permeable anastomosis and were able to achieve satisfactory erections
      resulting in normal intercourse. 92% of the patients with venous leak, 62.5% of
      those with arteriogenic impotence and 58% with mixed lesions had a successful
      results. Due to antithrombotic therapy, there was no graft occlusion. Glans
      hypervascularity occurred in 3 patients and was treated by arterial banding. The
      role of DDVA in vascular impotence and its functional mechanism are discussed.

PMID- 8307074
TI  - New intra-ureteral stent for use during reconstructive surgery.
AB  - This paper describes a stent which has been specifically designed to facilitate
      the identification of the ureters during lower urinary tract reconstruction. It
      has semi-rigid limbs which allow easy ureteric identification and a soft central
      portion which lies across the trigone without traumatising the ureteric orifices.

PMID- 8307075
TI  - Treatment system for nocturnal enuresis according to an original classification
      system.
AB  - Our department has reported recent studies for nocturnal enuresis. The morning
      bladder capacity in enuretic children was smaller in the 3- and 4-year-old age
      range but larger in the 7-year and over age range than that in nonenuretic
      children. 15% of nonenuretic children showed nocturnal polyuria with nocturnal
      urination after complete awakening more than once per week. It was not likely
      from this evidence that an immature bladder capacity or nocturnal polyuria was
      the primary cause of enuresis. Patients with enuresis were classified into three
      types based on overnight simultaneous monitoring by electroencephalography and
      cystometry. The pathogenesis of enuresis type I and type IIa was a disturbance of
      awakening, while that of type IIb was a disturbance of bladder function not shown
      in the daytime but only at night. An original systematic therapeutic plan was
      established with the development of an original therapeutic machine primarily for
      enuresis type I.

PMID- 8307076
TI  - Renal parenchymal thickness in children measured by computed tomography.
AB  - Renal parenchymal thickness was measured at different regions and levels through
      the kidney in 162 abdominal computed tomography (CT) examinations of children 5
      months to 14 years old. The transverse diameter of the first lumbar vertebra (L1)
      was also measured, in order to take into account the child's body habitus. All
      patients were examined with an indication other than renal disease and had no
      abnormal CT findings in the retroperitoneum. Renal parenchyma increased in
      parallel with the transverse diameter of L1 and did not depend on age or sex in
      children of the same body format. There were no significant differences in size
      between the right and the left kidneys. Renal measurements were tabulated on
      reference tables, as an aid in the assessment of renal parenchymal thickness in
      children undergoing abdominal CT examination.

PMID- 8307077
TI  - Experimental studies for clinical standardization of transabdominal laparoscopic
      nephrectomy.
AB  - In keeping with the maxim that minimal invasiveness is the present working trend
      in most areas of surgery, we investigated the possibility of laparoscopically
      removing a diseased human kidney. Before any actual clinical attempt could be
      made in this direction, an experimental study was set up in order to determine
      the most beneficial methods and techniques which would guide us through our first
      clinical cases. This step-by-step training program consists of: (1) initial
      familiarization with different laparoscopic instruments, bimanual dissection,
      ligation and coagulation techniques, camera handling and trocar placement as well
      as organ retrieval systems using the lap simulator; (2) laparoscopic removal of
      the kidney and ureter of the pig either as short- or long-term study, and (3)
      laparoscopic simulation with the lap tent during open surgery.

PMID- 8307078
TI  - Rat model for the study of penile erection: pharmacologic and electrical
      stimulation parameters.
AB  - We report the use of a modified rat model for the study of the mechanisms of
      penile erection. In 92 Sprague-Dawley rats, the cavernous nerve was stimulated
      with different pulse intensities and frequencies, and the intracavernous
      pressure, time to maximal pressure and total duration of tumescence were
      measured. A maximal response was elicited at 20 pulses per second (pps) and 1.5
      mA. Using this as 100%, we determined the relative pressure responses obtained
      with other frequencies: 5 pps, 57.3% (p = 0.007), 10 pps, 84.9% (p = 0.043); 30
      pps, 99.5% (p = 0.832); 40 pps, 97.8% (p = 0.168); 50 pps, 90.9% (p = 0.021); 100
      pps, 76.1% (p < 0.001). The time to maximal pressure varied with different
      frequencies, but was in all cases significantly different from the 20-pps
      response. Erection time during continuous cavernous nerve stimulation was
      significantly longer with frequencies below 20 pps (10 and 5 pps). In 30 rats,
      the physiologic response to intracavernous injection (0.03 ml) of acetylcholine,
      atropine, guanethidine, norepinephrine, phenylephrine, papaverine, terbutaline
      (intravenous also) and phentolamine was measured. Papaverine caused a dose
      dependent rise in pressure; acetylcholine, atropine (a parasympathetic blocking
      agent) and guanethidine all had minimal effects. Phentolamine and norepinephrine
      increased systemic blood pressure, whereas phenylephrine decreased the
      intracavernous pressure in response to electrostimulation significantly.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8307079
TI  - The Mainz pouch II.
AB  - The Mainz pouch II procedure has proved to be a substantial modification of the
      classical technique of ureterosigmoidostomy at many institutions. To date we have
      used this procedure in 72 patients, including 15 children. Detubularization
      causes a low pressure and eliminates high-pressure contractions. Without the risk
      of compromising the blood supply the pouch is fixed at the promontory which
      reduces the risk of ureteral kinking and upper urinary tract dilatation as it is
      sometimes observed after ureterosigmoidostomy. The technique is not only
      indicated in cases of failed ureterosigmoidostomy but also for primary urinary
      diversion. Of the 72 patients operated, all are evaluable with a follow-up of 1
      31 months. All patients are continent during the daytime with a mean emptying
      frequency of 5. All but one elderly woman are dry at night with a mean frequency
      of 1. The described urodynamic/rectodynamic evaluation enables a reliable
      prediction of postoperative continence. With the reservoir full the basal
      pressure was 24 cm H2O and the highest peak pressure recorded was 35 cm H2O.

PMID- 8307080
TI  - Decreased blood flow and defective energy metabolism in the varicocele-bearing
      testicles of rats.
AB  - This study was designed to elucidate the hemodynamic and energetic changes of
      testicles in experimental varicocele. Partial ligation of the left renal vein was
      performed in 10 Sprague-Dawley rats to induce dilatation of the internal
      spermatic vein, and sham operation was performed in the other 10 age-matched
      Sprague-Dawley rats used as controls. Blood pressure and rectal temperature were
      maintained at a constant level. Testicular blood flow was detected by laser
      Doppler flowmeter on the day before surgery and 4 weeks after surgery,
      respectively. Concentrations of various adenine nucleotides were determined by
      high-performance liquid chromatography (HPLC). We found a significant decrease
      from 10.2 +/- 1.5 to 7.4 +/- 1.8 mlLD/min/100 g (p < 0.005) in testicular blood
      flow after inducing varicocele in the rats. The energy charge of adenine
      nucleotides of the varicocele-bearing rats was 0.62 +/- 0.07 which was
      significantly lower than the 0.73 +/- 0.02 of the control group (p < 0.005).
      These observations have, thus, led us to propose the hypothesis that impaired
      spermatogenesis may result from defective energy metabolism in the varicocele
      bearing testicles of rats.

PMID- 8307081
TI  - The treatment of superficial bladder tumours under local anaesthetic using
      suction diathermy electrodes.
AB  - Daycase cystoscopy under local anaesthetic is commonly used in screening patients
      with superficial transitional cell carcinoma of the bladder. Treatment of any
      lesions found, however, often requires a further cystoscopy under general or
      regional anaesthesia. Recent reports suggest that small lesions can be
      diathermied without anaesthesia with only mild patient discomfort. Suction
      diathermy electrodes, introduced for the treatment of small superficial bladder
      tumours, have significant advantages over conventional methods. Firstly, most of
      the superficial tumour fronds can be removed painlessly by suction alone.
      Diathermy, the uncomfortable component of treatment, is sparingly used to treat
      the tumour base. Larger tumours can therefore be treated by suction diathermy,
      with less patient discomfort, than by standard cystodiathermy methods. Secondly,
      by eliminating tumour debris within the bladder during treatment and reducing
      tissue damage due to diathermy, suction diathermy minimizes the risk of tumour
      recurrence due to implantation. In this preliminary report the ease and efficacy
      of using suction diathermy electrodes under local anaesthesia is assessed.

PMID- 8307082
TI  - Negative testicular biopsy and asynchronous bilateral testicular germ cell
      tumour.
AB  - A case is described of a patient who was recently found to have a second primary
      testicular cancer 3 years after his first orchidectomy and negative contralateral
      testis biopsy.

PMID- 8307083
TI  - Bilateral laparoscopic ureterolysis.

PMID- 8307084
TI  - Posttraumatic priapism in a 7-year-old boy.
AB  - Priapism in childhood is most commonly a low-flow state due to sickle cell
      anemia. A high-flow priapism was seen in a 7-year-old boy following a straddle
      injury-induced arteriocavernosal fistula. Penile aspiration, intracorporeal alpha
      agonist injection and unilateral arterial embolization failed to resolve the
      priapism which eventually settled following a cavernosaphenous shunt.

PMID- 8307085
TI  - Mack-Forster Award 1993.

PMID- 8307086
TI  - 1993 Mack Forster Award Lecture. Review. The endothelium as a target and mediator
      of cardiovascular disease.

PMID- 8307087
TI  - Fraudulent (and non fraudulent) fatty acids for human health.

PMID- 8307088
TI  - Defects of leukocyte locomotion and chemotaxis: prospects, assays, and lessons
      from Chediak-Higashi neutrophils.

PMID- 8307089
TI  - Effect of transferrin concentration on bacterial growth in human ascitic fluid
      from cirrhotic and neoplastic patients.
AB  - Cirrhotic patients with ascites have an unusually high frequency of development
      of spontaneous bacterial peritonitis. Iron availability is a key factor in
      bacterial growth and the ability of the host to limit it is associated with
      resistance to infection. The present study was undertaken to evaluate the
      influence of iron and transferrin on bacterial growth in ascitic fluid from 25
      biopsy-proven cirrhotic and nine neoplastic carcinomatous patients. No
      significant differences were found when comparing total ascitic fluid iron
      between the two groups but ascitic fluid transferrin concentration was
      significantly lower in cirrhotic (29.26 mg dl-1 SD 29.58) than neoplastic (96.57
      mg dl-1 SD 76.01) patients. Moreover, a significant negative correlation was
      found between bacterial growth and transferrin concentration in ascitic fluid (P
      = 0.039). When the iron concentration in ascitic fluid was experimentally
      elevated (50 micrograms dl-1 or 150 micrograms dl-1) we observed a progressive
      increase in bacterial growth. If transferrin concentration is simultaneously
      elevated (250 mg dl-1) this increase does not occur. These findings indicate that
      the transferrin level is an important factor in the regulation of bacterial
      growth in ascitic fluid and that the low concentration found in cirrhotic
      patients could facilitate spontaneous bacterial peritonitis.

PMID- 8307090
TI  - Influence of intravenous n-3 lipid supplementation on fatty acid profiles and
      lipid mediator generation in a patient with severe ulcerative colitis.
AB  - N-3 fatty acids were supplied to a 36-year-old female patient suffering from
      ulcerative colitis and severe steroid side-effects, in a sequence of parenteral
      and enteral administration. During a moderately active period of disease, 200 ml
      d-1 fish oil-derived lipid emulsion (eicosapentaenoic acid [EPA], 4.2 g;
      docosahexaenoic acid [DHA], 4.2 g) was infused for 9 days, in parallel with rapid
      tapering of the steroid dose. Disease activity declined rapidly, and the patient
      was subsequently provided with 16 fish oil capsules per day (EPA, 2.9 g; DHA, 1.9
      g) for 2 months. At the end of this period of therapy, severe colitis recurred
      with intestinal and extraintestinal manifestations. The n-3 lipid emulsion was
      then used for intravenous alimentation (29 days, maximum dose 300 ml per day);
      during this time, marked improvement of the inflammatory bowel disease was noted.
      During both periods of parenteral n-3 lipid administration, total plasma EPA and
      DHA contents increased several-fold, surpassing that of arachidonic acid; this
      plasma n-3 fatty acid enrichment was only maintained to a minor extent during the
      intermediate period of dietary fish oil supplementation. The intravenously
      administered EPA-containing triglycerides were rapidly hydrolyzed, as evidenced
      by the appearance of substantial quantities of EPA in the plasma free fatty acid
      fraction. Platelet and neutrophil total membrane content of EPA and DHA as well
      as n-3 fatty acid/AA membrane ratios similarly increased during the periods of
      intravenous n-3 lipid administration and declined during oral fish oil
      uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307091
TI  - The effect of porphyrins on cellular redox systems: a study on the dark effect of
      porphyrins on phagocytes.
AB  - Erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT) are
      characterized by skin morbidity, induced by pro-inflammatory reactive oxygen
      species generated by the photosensitizing properties of protoporphyrin IX and
      uroporphyrin I. How these porphyrins exert a toxic effect on the liver in the
      absence of light is poorly understood. We tested the hypothesis that porphyrins
      can interference with cellular redox systems, by studying the dark effects of
      protoporphyrin (PP), haematoporphyrin (HP), deuteroporphyrin (DP) and
      uroporphyrin (UP) on the cellular redox system of phagocytes, and on enzymatic
      oxyradical generating systems. Both in phagocytic cells and enzymatic systems, a
      dose-dependent inhibition of chemiluminescence was observed by all porphyrins
      added. Catalase and SOD-like activity of porphyrins was excluded by oxygraph and
      ferricytochrome c reduction. However, ferrocytochrome c oxidation was inhibited
      by porphyrins indicating ferrireductase-like activity. In a Fenton type reaction
      between H2O2 and PP, we could demonstrate the generation of .OH, or an
      electronically excited porphyrin species. No influence on phagocyte chemotaxis,
      phagocytosis and killing-capacity was observed. We conclude that porphyrins do
      interfere with (cellular) redox systems and can both inhibit and enhance oxygen
      free radical generation, dependent on the type of redox reaction. Porphyrins can
      thus affect cellular metabolism. Since H2O2 and PP both readily dissolve in
      biological membranes, their interaction in the presence of transition metals may
      contribute to the toxic dark effects of porphyrins as observed in patients with
      EPP and PCT.

PMID- 8307092
TI  - Abdominal and femoral adipose tissue lipolysis and cardiovascular disease risk
      factors in men.
AB  - The relationships between subcutaneous abdominal and femoral fat cell lipolyses,
      plasma free-fatty acid (FFA) levels and metabolic variables considered as risk
      factors for cardiovascular disease (CVD) (plasma glucose, insulin and lipoprotein
      levels) were investigated in 54 men, aged 36 +/- 3 (SD) years, covering a wide
      range of body fatness values (body mass indices from 19 to 34 kg m-2). Although
      there were no consistent relationships between femoral fat cell weight and the
      metabolic profile, positive and significant associations were found between
      abdominal fat cell weight and most of the metabolic indices. However, abdominal
      fat cell lipolysis measured with an alpha 2-(clonidine) or a beta-agonist
      (isoproterenol) was unrelated to metabolic variables. In contrast, femoral fat
      cell lipolysis measured in the presence of clonidine was positively associated
      with fasting plasma insulin, cholesterol (CHOL) and apolipoprotein (apo) B
      levels, as well as with LDL-CHOL and LDL-apo B concentrations. No association was
      found between isoproterenol-stimulated lipolysis of femoral adipocytes and the
      metabolic profile. Comparison of two subgroups of men with either low or high
      femoral residual lipolysis with clonidine revealed that subjects with the lowest
      femoral alpha 2-adrenergic component (i.e. the highest residual lipolysis)
      displayed significant alterations in both plasma lipid-lipoprotein and glucose
      insulin levels which could be predictive of an increased risk of CVD. Free fatty
      acid (FFA) levels measured in the fasting state and during an oral glucose
      tolerance test (OGTT) were positively associated with fasting plasma insulin and
      triglyceride levels as well as with both glucose and insulin areas measured
      during the OGTT. However, regional adipose tissue lipolysis measured in vitro was
      unrelated to plasma FFA levels. These results support the view that both femoral
      adipose tissue lipolysis and plasma FFA levels are significant correlates of
      plasma glucose-insulin homeostasis and lipoprotein-lipid levels, in men. However,
      as adipose tissue lipolysis and plasma FFA are unrelated to each other, they may
      be associated with risk variables through independent mechanisms.

PMID- 8307093
TI  - The impact of intermittent claudication on quality of life evaluated by the
      Sickness Impact Profile technique.
AB  - Unselected patients suffering from intermittent claudication (n = 148) were
      invited to take part in a prospective study. Physical examination and several
      circulatory investigations were performed including a treadmill walking test,
      bicycle ergometry and a quality of life examination (Sickness Impact Profile,
      SIP, technique). The SIP has been reported to be sensitive enough to identify
      specific dysfunction profiles in several clinical conditions, but it has not been
      used on patients with intermittent claudication. The aim of this study was to
      determine to what extent quality of life was influenced by reduced walking
      ability in patients with intermittent claudication. If so, the SIP technique
      should then be a useful tool for determination of the degree of reduced exercise
      capacity in patients who may benefit from surgery instead of conservative
      treatment. A majority of the SIP categories, Sleep and rest, Emotional behaviour,
      Body care and movement, Home management, Mobility, Social interaction, Ambulation
      and Overall SIP were shown to be useful in confirming objective dysfunctions in
      our patients. The correlation between maximum walking ability and SIP scores
      indicated an approximate cut-off limit at 70 W walking capacity. Thus,
      significant reductions in everyday life function were demonstrated in patients
      with maximum walking ability below 70 W. Patients with intermittent claudication
      also suffered from several other dysfunctions in addition to walking disability.
      These factors may, as well, impact on quality of life without walking disability.
      Our results demonstrated that quality of life assessment by the SIP technique was
      a sensitive method for evaluation of overall dysfunction in patients with
      intermittent claudication.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307094
TI  - Non-steady-state kinetics of low density lipoproteins in man: studies after
      plasma exchange in healthy subjects and patients with familial
      hypercholesterolaemia.
AB  - Five patients with heterozygous familial hypercholesterolaemia (FH), one patient
      with non-familial hypercholesterolaemia, and four healthy normals were treated
      with plasma exchange (PE). In order to achieve a non-steady-state situation with
      low plasma cholesterol levels, PE was performed twice in each subject at an
      interval of 1-3 days. At each time, 1500 ml of plasma were removed and replaced
      with colloids and albumin. Lipoprotein analyses were performed daily in all
      subjects for a period of 14 days following PE. Kinetic calculation of LDL
      cholesterol data using a two-compartment open model was performed, and rate
      constants, synthetic rate and apparent clearance of LDL were determined. A lower
      clearance and a tendency towards a higher synthesis of LDL were observed in the
      FH patients. In four of the subjects, LDL kinetics was also studied with the
      conventional 125I-LDL turnover technique. The synthetic rates of LDL were
      compared using data derived from PE and 125I-LDL kinetics. The two techniques
      showed a good correlation (r = +0.93) although synthetic rates in general were
      higher when calculated from the 125I-LDL procedure (3.98 vs. 2.64 mmol d-1 for
      LDL cholesterol synthesis). The results indicate that non-steady-state kinetics
      of LDL, as measured using the PE technique, is a useful method for analysis of
      LDL metabolism.

PMID- 8307095
TI  - Human intestinal alkaline phosphatase--release to the blood is linked to lipid
      absorption, but removal from the blood is not linked to lipoprotein clearance.
AB  - To evaluate a possible quantitative relationship between the rise in intestinal
      alkaline phosphatase (IAP) activity and triglyceride-rich lipoproteins in the
      blood after an oral fat intake, a specific and sensitive immunocatalytic assay
      was used. First, day to day variation of the basal IAP activity in the blood of
      eight volunteers was evaluated. One group of subjects with high basal IAP
      activity and great variations from one day to the other was distinguished from a
      group with low basal IAP activity and small day to day variations. The subjects
      with high basal IAP activities were all secretors of red blood cell antigens,
      while those with low basal IAP activities were non-secretors. The IAP activity in
      the blood rose after fat rich meals but not after fat free meals. To further
      investigate this, IAP activities were measured in the blood of 28 men before 3,
      6, 9 and 12 h after a standardized oral fat load of a mixed meal type. The
      activity rose in all individuals and showed a similar time course as the rise in
      plasma TG concentration. The elevations of the IAP activity were, however, not
      quantitatively correlated with the elevations in TG concentration, nor were there
      any relations in time to peak levels. Subjects with high basal IAP increased
      their IAP activity more than those with low basal IAP, but within neither group
      there was any correlation between the basal IAP activity and the rise in IAP
      activity. IAP did not float with lipoproteins on ultracentrifugation of plasma,
      nor did IAP bind to lipid droplets from a fat emulsion added to plasma.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8307096
TI  - Increased alpha 1B-adrenoreceptor mRNA levels in the rat kidney after
      thyroidectomy.
AB  - Oligonucleotide probes were designed to sequences of the rat alpha 1B- and alpha
      2B-adrenergic receptor mRNA and used for in situ hybridization histochemistry on
      tissue sections of kidneys from control and thyroidectomized rats. Both alpha 1B-
      and alpha 2B-receptor mRNA labelling was demonstrated in proximal tubule cells in
      the outer stripe of the outer medulla, with tubular rays radiating into the
      cortex. Thyroidectomy induced a more than 4-fold increase in mRNA for the alpha
      1B-receptor in the kidney, whereas no change in alpha 2B-receptor mRNA levels
      could be demonstrated in thyroidectomized rats as compared to control animals.
      The results suggest that thyroid hormone plays an important role in regulating
      expression of alpha 1B-receptors in renal tubule cells.

PMID- 8307097
TI  - Structure-activity relationships of serotonin transport: relevance to
      nontricyclic antidepressant interactions.
AB  - A transfectant cell model was used to examine the structure-activity
      relationships of serotonin (5-hydroxytryptamine, 5-HT) transport. The findings
      suggest that 5-HT interacts largely with nonpolar and sterically-confining
      environments on the transport system, and that a particular spatial coordination
      of the amino and phenyl groups (separated by an alkyl backbone) is important for
      transport interaction. Molecular modelling analyses revealed that this motif is
      also present in the structures of several nontricyclic antidepressants and
      specific inhibitors of 5-HT transport, as well as adrenergic agents which also
      possess 5-HT transport-inhibitory activities. While this amino-phenyl
      coordination motif seems to be a necessary structural requisite for transport
      interaction, and therefore likely to be part of the transport pharmacophore,
      additional phenyl rings present in some of the nontricyclic antidepressants may
      help to account for their relatively higher affinities in 5-HT transport
      interaction.

PMID- 8307098
TI  - Phenoxybenzamine mediated inhibition of the vascular dopamine D1 receptor.
AB  - Cultures of rat mesenteric artery vascular smooth muscle cells express both
      vascular dopamine D1 receptors and beta 2-adrenoceptors but not alpha 1- or alpha
      2-adrenoceptors, permitting direct investigation of the dopamine D1 receptor
      antagonist activity of phenoxybenzamine. After incubating cells with
      phenoxybenzamine (10(-5) M) for 20 min, an 80% inhibition of dopamine-induced
      (10(-4) M) cAMP formation was observed. Isoprenaline-induced (10(-5) M) cAMP
      formation remained unaffected by phenoxybenzamine. Inhibition of the dopamine
      response following 20 min incubation with phenoxybenzamine, was concentration
      related and could not be reversed by repeated washing. Mean IC50 (95% confidence
      limits) = 4.68 x 10(-6) M (3.86-5.01). Exposure of cells to the selective
      dopamine D1 receptor partial agonist (+)-SKF 38393 (10(-6) M) prior to
      phenoxybenzamine incubation, resulted in protection of dopamine-induced cAMP
      formation. Exposure of cells to the stereo-enantiomer (-)-SKF 38393 (10(-6) M)
      did not produce any protective effect. The concentration-effect curve for (+)-SKF
      38393 mediated protection had a mean EC50 value of 0.11 x 10(-6) M (0.10-0.11),
      which is comparable with the Ka apparent value (0.06 x 10(-6) M) for this
      compound when acting as an agonist to induce cAMP formation via the vascular
      dopamine D1 receptor. Previous studies of the vascular dopamine D1 receptor are
      likely to have been influenced by the frequent use of phenoxybenzamine, which we
      have shown to act as a potent antagonist at this site.

PMID- 8307099
TI  - Allosteric potentiation by diazoxide of AMPA receptor currents and synaptic
      potentials.
AB  - Diazoxide (100-560 microM) reversibly increased the amplitude and duration of
      excitatory post-synaptic field potentials recorded in the dentate gyrus of
      hippocampal slices following stimulation of the perforant pathway. In rat cortex
      mRNA-injected Xenopus oocytes diazoxide (1-1000 microM) alone had little effect
      on membrane current, but rapidly and reversibly increased (up to 5-fold) current
      responses to (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid
      (AMPA, 30 microM), L-glutamate (100 microM), quisqualate (3 microM), kainate (100
      microM) and domoate (3 microM), an effect that was neither mimicked by other
      activators of ATP-sensitive potassium channels nor blocked by glibenclamide.
      Diazoxide increased current amplitudes for all concentrations of the
      'inactivating' ligands, AMPA, L-glutamate and quisqualate but had little effect
      on their EC50 values. In contrast, diazoxide increased the apparent potency of
      the 'non-inactivating' ligands, kainate and domoate, but increased the efficacy
      of saturating concentrations by only 10-20%. Diazoxide did not modify the
      competitive inhibition of AMPA and kainate currents by 6-nitro-7
      sulfamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and thus does not compete for the
      agonist site as do AMPA and kainate. Similarly, diazoxide neither inhibited the
      binding of [3H]AMPA or [3H]kainate to rat cortical membranes in competition
      experiments nor consistently modified the apparent [3H]AMPA affinity (Kd) or
      receptor density (Bmax) in saturation experiments. These data suggest that
      diazoxide acts at an allosteric site on the AMPA receptor/channel to potentiate
      activation in a manner dependent upon the properties of the excitatory agonist.

PMID- 8307100
TI  - Effects of local anesthetics and related drugs on endogenous glibenclamide
      sensitive K+ channels in Xenopus oocytes.
AB  - Effects of local anesthetics and structurally related drugs on the glibenclamide
      sensitive K+ currents evoked by Y-26763 (a K+ channel opener) were investigated
      in native Xenopus oocytes. The K+ current induced by Y-26763 (100 microM) was
      reversibly suppressed by all six local anesthetics tested in a concentration
      dependent manner with the rank order of potencies (IC50 in microM): bupivacaine
      (67) > dibucaine (136) > tetracaine (845) > lidocaine (1710) = mepivacaine (1945)
      > procaine (3112). (+)-Propranolol and mexiletine also suppressed Y-26763-induced
      K+ currents with IC50 values of 115 microM and 789 microM, respectively. These
      results suggest that a suppressive action on glibenclamide-sensitive K+ channels
      is the common property of local anesthetics.

PMID- 8307101
TI  - Polyamine-enhanced NMDA receptor activity: effect of ethanol.
AB  - The effect of ethanol on spermidine-enhanced, N-methyl-D-aspartate (NMDA)-induced
      seizures and c-fos expression was investigated in the rat brain. The latency of
      tonic-clonic convulsions induced by i.p. administration of NMDA (50 mg/kg) was
      decreased by prior i.c.v. injection of spermidine (0.1-2.5 mumol) in a dose
      dependent manner. Neither NMDA (50 mg/kg) nor spermidine (up to 2.5 mumol) alone
      induced c-fos mRNA expression in the brain. When both agents were administered,
      significant induction of c-fos expression occurred 30 min after the convulsion.
      Prior treatment with ethanol did not alter the curve of spermidine dose
      dependency over most of the range. The c-fos expression induced by a combination
      of NMDA (50 mg/kg) and spermidine (1.0 mumol) was unaffected by ethanol. Only at
      a high dose of ethanol (2.0 g/kg) and at minimal spermidine enhancement was NMDA
      induced seizure and c-fos expression inhibited. These results suggest that
      polyamines may have an important role in modulating NMDA receptor function in
      vivo and that polyamine enhancement of NMDA receptor function is relatively
      insensitive to the inhibitory effects of ethanol.

PMID- 8307102
TI  - Tolerance to the effects of diazepam, clonazepam and bretazenil on GABA
      stimulated Cl- influx in flurazepam tolerant rats.
AB  - The effect of chronic flurazepam treatment on the GABA (gamma-aminobutyric acid)
      receptor/chloride channel complex was studied using GABA-stimulated 36Cl- influx
      into brain microsacs, and its potentiation by diazepam, clonazepam and
      bretazenil. Rats were given flurazepam for 1 week, then microsacs were prepared
      from cerebral cortices of rats that were still receiving flurazepam, and from
      those that had stopped treatment 48 h earlier. Diazepam and clonazepam produced
      concentration-dependent increases in GABA-stimulated 36Cl- influx while
      bretazenil produced a much smaller effect, which did not reach statistical
      significance in the tissue from control rats. There was no significant change in
      the basal or 10 microM GABA-stimulated 36Cl- influx between control and treated
      groups. Tolerance was shown by a significantly reduced effect of diazepam and
      clonazepam to enhance GABA-stimulated 36Cl- influx in the tissue prepared from
      non-withdrawn rats. However, for both diazepam and clonazepam, there was no
      tolerance 48 h after chronic treatment. The results suggest that changes in the
      GABA receptor/Cl- channel complex on cerebral cortical neurons contribute to
      cross-tolerance from flurazepam to other benzodiazepines.

PMID- 8307103
TI  - Characterisation of the binding of [3H]FR115427, a novel non-competitive NMDA
      receptor antagonist, to rat brain membranes.
AB  - The binding of [3H]FR115427 ([3H](+)-1-methyl-1-phenyl-1,2,3,4-
      tetrahydroisoquinoline) to rat cortical synaptosomal membranes was investigated.
      Binding was optimal at pH 7.4-8.0, and temperature had little effect on specific
      binding. Binding reached equilibrium within 30 min at 25 degrees C, and was
      reversible in the presence of excess unlabelled FR115427. [3H]FR115427 bound to a
      single population of non-interacting sites with an affinity of 45.4 +/- 3.9 nM,
      and a binding site density of 9.12 +/- 0.52 pmol/mg protein. The affinities of
      other N-methyl-D-aspartate (NMDA) receptor channel blockers for [3H]FR115427
      binding sites were consistent with binding to a similar site to that occupied by
      dizocilpine. Binding was potentiated by L-glutamate and glycine with EC50 values
      of around 80 nM. In the presence of L-glutamate (10 microM), specific binding was
      increased 4-fold, whilst addition of glycine (10 microM) increased specific
      binding 2-fold. FR115427 exhibited marked stereoselectivity; (+)-FR115427 has 100
      fold higher affinity than (-)-FR115427. This ligand may therefore be useful for
      the pharmacological investigation of the NMDA receptor ion channel.

PMID- 8307104
TI  - Ca2+ and Ca2+ channel antagonists in the control of human small cell lung
      carcinoma cell proliferation.
AB  - Small cell lung carcinoma cells possess voltage-dependent calcium channels
      (VDCCs) of the L, omega-conotoxin-sensitive and P-like type. We hypothesized that
      these VDCCs might regulate the secretion of autocrine growth factors and thus
      influence the proliferation of these cells. We found that extracellular Ca2+
      plays a stimulatory role in the proliferation of the GLC8 cell line. L-type
      calcium channel blockers of the dihydropyridine, phenylalkylamine and
      benzothiazepine classes inhibited [3H]thymidine incorporation in these cells,
      however at concentrations higher than those required to block L-type channel
      function. Moreover, the growth of murine Swiss 3T3 fibroblasts which do not
      possess L-type Ca2+ channels, was inhibited by the Ca2+ channel antagonists at
      the same effective concentrations as in small cell lung carcinoma cells. omega
      conotoxin and omega-agatoxin IVA, which block the N- and P-type channel
      respectively, had no effect on GLC8 cell proliferation. It is concluded that the
      presence of extracellular Ca2+ is a positive stimulus for small cell lung
      carcinoma cell growth. However, under our experimental conditions, the calcium
      channel blockers inhibited DNA synthesis most probably by a mechanism other than
      VDCC antagonism.

PMID- 8307105
TI  - Specific binding of [3H]GBR 12783 to the dopamine neuronal carrier included in
      polarized membranes.
AB  - We have compared the properties of the binding to the neuronal dopamine carrier
      located either in polarized membranes of synaptosomes or in non polarized,
      classical membranes. Non-polarized membranes were prepared by sonication of the
      partially purified synaptosomal fraction obtained from rat striatum which was
      used as the source of polarized membranes. Binding experiments were carried out
      at 37 degrees C in Krebs Ringer related media. [3H]GBR 12783 (1-[2
      (diphenylmethoxy)ethyl]4-(3-phenyl-2-[1- 3H]propenyl)piperazine) specifically
      bound with a nanomolar affinity to a homogeneous population of site (maximal
      binding site concentration: 8-10 pmol/mg protein). Pure uptake inhibitors, but
      not substrates, competed for the [3H]GBR 12783 binding site located in polarized
      membranes of synaptosomes at concentrations effective against dopamine neuronal
      transport. Except for [3H]GBR 12783, the replacement of Cl- by isethionate- did
      not result in significant change in the ability of pure uptake inhibitors to
      compete for the specific binding site. A reduction in the Na+ concentration from
      135 to 10 mM induced a significant decrease in the inhibitory potency of GBR
      12783, mazindol, nomifensine and methylphenidate. This decrease was likely to
      result from the presence of K+, Mg2+ and Ca2+, whose inhibitory effects were
      modified and/or increased by decreasing the Na+ concentration. These data
      indicate that the membrane polarity is not clearly involved in the binding of
      pure uptake inhibitors to the dopamine neuronal carrier; furthermore they
      underline the critical role of Na+ and K+ transmembrane gradients in both the
      recognition of the carrier by dopamine and its inward transport.

PMID- 8307106
TI  - [3H]gabapentin may label a system-L-like neutral amino acid carrier in brain.
AB  - The ability of large neutral amino acids to interact with a site in mouse and pig
      brain labelled by [3H]gabapentin was examined. As previously described for rat
      tissue, [3H]gabapentin bound to synaptic plasma membranes prepared from mouse or
      pig cerebral cortex with high affinity (Kinetically derived KD = 14 and 17 nM for
      mouse and pig, respectively). Equilibrium binding in each species was inhibited
      by gabapentin and a range of large neutral amino acids. L-leucine (IC50 = 80 nM),
      L-isoleucine (IC50 = 72 nM), L-norleucine (IC50 = 40 nM) and L-methionine (IC50 =
      50 nM) were the most potent of those tested. Binding was also inhibited by L
      phenylalanine (IC50 = 380 nM), L-valine (IC50 = 310 nM) and the selective system
      L substrate 2-amino-2-carboxy-bicycloheptane (IC50 = 420 nM) but not by the
      sodium-dependent System-A substrate methylaminoisobutyric acid. The presence of a
      submaximal concentration of leucine reduced [3H]gabapentin binding affinity but
      did not affect the maximum number of binding sites, suggesting a competitive
      interaction between leucine and the binding protein. The results suggest
      [3H]gabapentin may label a site in brain that resembles the large neutral amino
      acid transporter described in other tissues.

PMID- 8307107
TI  - Mg2+ modulates the binding of [3H]glibenclamide to its receptor in rat cerebral
      cortical membranes.
AB  - Radioligand binding studies were performed to determine the effect of various
      cations on the characteristics of [3H]glibenclamide binding to its high-affinity
      receptor in rat cerebral cortex membranes. Mg2+ was shown specifically to reduce
      radioligand binding to membranes pretreated with 5 mM EDTA. CaCl2 enhanced
      [3H]glibenclamide binding whilst MnCl2, KCl and NaCl were without significant
      effect. 2 mM MgCl2 induced a statistically significant rightward shift in the
      dissociation constant for glibenclamide obtained from both saturation and
      competition studies. These results suggest that Mg2+ may participate in the
      regulation of the sulphonylurea receptor in the rat cerebral cortex.

PMID- 8307108
TI  - Unexpected contractile response from the G-protein activator mastoparan in
      cardiac myocytes.
AB  - Mastoparan preferentially activates the G protein Gi in transmembrane signalling
      pathways. In heart tissue Gi couples receptors to negative inotropy so we have
      examined the effect of mastoparan on contractility in cardiac myocytes
      electrically stimulated at 0.5 Hz. Mastoparan (10(-5) mol/l) caused a time
      dependent increase in cell shortening to a maximum of 83.7 +/- 18.0% (n = 7) of
      the resting cell length at between 4 and 7 min. This could be the result of
      either stimulation of other G proteins or the release of beta gamma subunits from
      Gi which activate phospholipase C.

PMID- 8307109
TI  - Estrogen use and cancer risk: a review.
AB  - The role of estrogens as carcinogens, cocarcinogens or tumor promoters, as well
      as their mechanism(s) of action on cancer cells, are thoroughly reviewed.
      Although there is ample evidence that estrogens (natural and synthetic) can
      induce multiple benign and malignant tumors in animals, and most of these tumors
      are histologically similar to that in humans, there is no direct evidence that
      natural estrogens (estradiol-17 beta, estrone) are carcinogenic in humans. Recent
      evidence in cellular and molecular oncology revealed that estrogens act by
      genetic and epigenetic mechanisms on cancer cells, and a close relationship
      between estrogens, growth factors, and oncogenes is important for human cancer.
      Long-term exposure to estrogens should always be regarded as increased cancer
      risk. Estrogen replacement therapy (ERT) by unopposed estrogens in postmenopausal
      women with high familial cancer risk or existent premalignant lesions should be
      avoided, since estrogens may act as tumor promoters. Combination of estrogens
      with progesterone (or other progestins) cyclically or sequentially, significantly
      reduce and prevent the cancer risk.

PMID- 8307110
TI  - Chronic insulin treatment, but not chronic ACTH administration increases plasma
      dehydroepiandrosterone sulfate levels in adolescent male rats.
AB  - The chronic effect of daily i. m. administration of ACTH (1 U/kg bodyweight (BW),
      group A) and of insulin (15/kg BW, group B) on circulating dehydroepiandrosterone
      sulfate (DHEA-S) and testosterone was investigated in postpubertal male Wistar
      rats. NaCl-injected animals served as controls (group C). After at least 8 days
      under the respective hormone or NaCl treatment "basally" circulating testosterone
      levels were slightly suppressed in insulin- (1.56 +/- 0.86 ng/ml) and markedly
      reduced (0.54 +/- 0.21 ng/ml) in ACTH-treated rats vs. controls (2.33 +/- 0.69
      ng/ml). DHEA-S levels, however, nearly doubled under chronic insulin
      administration (0.4 +/- 0.18 ng/ml) in comparison to the groups A (0.22 +/- 0.11
      ng/ml) and C (0.23 +/- 0.09 ng/ml). Food intake and weight gain were also
      elevated (vs. groups A and C) as were the basal plasma corticosterone levels (vs.
      group C) in insulin treated rats. Following an acute ACTH stimulation test (12
      U/kg BW i.m.) performed in all three treatment groups, plasma DHEA-S showed a
      further increase in the animals receiving insulin (0.75 +/- 0.32 ng/ml), whereas
      no response was detectable in rats from group A (0.27 +/- 0.13 ng/ml) or C (0.24
      +/- 0.11 ng/ml). Further measurements of corticosterone or testosterone responses
      following endocrinological stimulation tests with supraphysiological doses of
      either ACTH or human chorionic gonadotropin (hCG) indicated that a lowering in
      the catabolism (metabolic clearance) of corticosteroids or androgens could not be
      the cause for the elevated DHEA-S levels seen after daily insulin
      injections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307111
TI  - Effect of protein deficiency on luteinizing hormone releasing hormone (LHRH),
      gonadotropin releasing hormone associated peptide (GAP) and luteinizing hormone
      (LH) immunocytochemistry in the hypothalamus and pituitary gland of prepubertal
      ewes.
AB  - Growing female lambs were fed diets containing 14.2% (standard) or 8.1% (protein
      restricted) of proteins to determine their effects on puberty and luteinizing
      hormone releasing hormone (LHRH), gonadotropin hormone associated peptide (GAP),
      luteinizing hormone (LH) hormonal system. At the end of the experiment (30-34
      weeks of age), hypothalamic LHRH, GAP and pituitary LH were analysed by
      immunocytochemical methods using specific antibodies. Plasma LH were determined
      by radioimmunoassay at 21 weeks of age. It was found that lowering of the dietary
      proteins content decreased the concentration of basal plasma LH significantly in
      lambs of 21 weeks of age. None of the sheep of this group reached sexual maturity
      at the same time as the animals of the standard group. However, immunoreactive
      (ir) LHRH neuronal system of protein restricted lambs was normally developed:
      Numerous irLHRH perikarya, dense network of axons and abundant material stored in
      the nerve terminals were well visualized in the typical sites of the preoptico
      septal area, hypothalamus and the median eminence (ME). Gonadotropin associated
      peptide (GAP) of the LHRH precursor was present in the same populations of
      neurons that contained LHRH in the sheep brain. The proportion of pituitary LH
      cells was three fold higher in pituitaries of the nutritionally restricted group.
      They displayed hypertrophy and very strong immunoreaction. These results show
      that protein deficiency in diets of growing female sheep delays their puberty but
      does not impair the synthesis and processing of LHRH in the brain neurons and
      synthesis of LH in pituitary cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307112
TI  - In vitro effects of ethanol on gonadotropin-binding sites in porcine granulosa
      cells.
AB  - In this study, we examined the in vitro effects of ethanol on [125I]human
      follicle-stimulating hormone (hFSH) and [125I]human luteinizing hormone (hLH)
      binding to porcine granulosa cells (GCs). The GC suspensions and [125I]hFSH or
      [125I]hLH were incubated in the presence or absence of 1-50% (vol/vol) ethanol
      until steady state binding was attained for 2 h at 37 degrees C. The presence of
      1-4% ethanol significantly enhanced the specific binding of hFSH to porcine GCs,
      with a maximal effect at 4% ethanol, however, had no effect on hLH binding.
      Higher concentration of ethanol (8-50%) significantly decreased both specific
      hFSH and hLH binding to porcine GCs. Scatchard analyses revealed that ethanol
      increased the number of FSH-binding sites without changing the affinity for FSH.
      The data suggest that porcine GCs contain a population of masked FSH-binding
      sites exposed by in vitro treatment with ethanol. Furthermore, the membrane
      fluidity may play an important role in the masking/unmasking mechanism of FSH
      binding sites within the porcine GCs.

PMID- 8307113
TI  - Effects of thyroid hormone status on the growth hormone responses to clonidine.
AB  - It has been shown that thyroid hormones are positive regulators of GH synthesis
      and secretion. The serum GH response to stimuli seems to be influenced either by
      sex or by spontaneous hypothalamic rhythm. The growth hormone responses to
      clonidine administration (4 micrograms/kg) have been therefore studied in a group
      of female patients with thyroid disease (seven hyperthyroid and five hypothyroid)
      before and after the achievement of the euthyroid state. In hyperthyroid patients
      both basal and clonidine-stimulated GH levels were similar to normal subjects;
      the achievement of euthyroidism did not modify the GH response to clonidine.
      Serum GH peaks after clonidine were lower in hypothyroids patients than in
      hyperthyroids and normal subjects; the GH response to alpha 2-agonist
      administration did not change during thyroid replacement therapy. The GH response
      to clonidine was not influenced by the GH secretory status in the preceding hour.

PMID- 8307114
TI  - Increased serum neopterin levels in patients with Graves' disease.
AB  - Neopterin (NPT) a marker of activation of the T-lymphocyte/monocyte axis has been
      measured in serum of 89 patients with autoimmune thyroid disease (72 patients
      with Graves' disease and 17 patients with autoimmune thyroiditis) and compared to
      a group of 24 normal controls and 24 patients with nontoxic goitre. There was a
      significant correlation between NPT levels and age in the patients with nontoxic
      goitre (r = 0.447, p < 0.001) but not in patients with autoimmune thyroid
      disease. Significantly higher NPT levels were found in all patients with Graves'
      disease (GD) compared to age and sex matched healthy controls, and patients with
      nontoxic goitre (5.7 +/- 2.4 vs 4.1 +/- 1.7, and 4.0 +/- 1.5, p < 0.01). However,
      there was no difference in NPT levels between each group of patients with GD when
      subdivided in: hyperthyroid newly diagnosed GD, treated GD, GD in remission and
      relapse. Patients with autoimmune thyroiditis did not have abnormal NPT levels
      compared to age and sex matched normal controls. Neopterin serum levels were not
      influenced by hyperthyroidism as no significant differences in NPT levels could
      be found in 24 patients with hyperthyroid Graves' disease and 13 patients with
      toxic goitre or toxic adenoma when compared to age and sex matched euthyroid
      patients with Graves' disease or normal controls. Moreover, there was no
      significant difference in mean NPT levels 1. before and after restoration of
      euthyroidism in 10 patients with hyperthyroid Graves' disease and 2. before and
      under T3 supplementation in 18 patients with Graves' disease in remission who
      underwent a T3 thyroid suppression test.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307115
TI  - Different steroidogenic response of young and aged porcine small and large luteal
      cells to prostaglandin F2 alpha, oxytocin and estradiol.
AB  - The role of oxytocin (OXT) and prostaglandin F2 alpha (PGF2 alpha) in the process
      of luteal regulation, particularly their function in the early luteal phase is
      poorly understood. Therefore the effects of both compounds on in vitro steroid
      release of porcine luteal cells harvested from young/middle-aged (day 4-6, day 0
      = 1st estrous day) or old (day 12-14) corpora lutea were tested. As corpora lutea
      (CL) contain at least two different steroidogenic cell populations, fractions of
      the so called small (SLC) and large (LLC) luteal cells were prepared and tested
      in separate experiments. In SLC as well as LLC from young CL OXT and PGF2 alpha
      inhibited progesterone (P) production but induced a strong increase of estradiol
      (E2) release. In old SLC and LLC OXT and PGF2 alpha were still inhibitory to P
      release but OXT was ineffective and PGF2 alpha had a moderate stimulatory effect
      on luteal E2 secretion. In SLC cultures from young but not from old CL E2 exerted
      a powerful stimulatory effect on progesterone (P) secretion, i.e. E2 has strong
      luteotrophic effects in the early luteal phase. Indeed, the pronounced inhibitory
      effect of OXT and PGF2 alpha on P release from SLC could be counteracted by the
      addition of exogenous E2 to the culture media. Therefore, we suggest that in the
      early luteal phase OXT as well as PGF2 alpha have an indirect, E2-mediated
      luteotrophic effect on P release which is stronger than the direct inhibitory
      action on P secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307116
TI  - Stimulatory action of porcine follicular fluid on granulosa cell secretion of
      cyclic GMP.
AB  - Effects of FSH, LH and follicular fluid isolated from preovulatory follicles on
      secretion of progesterone, cAMP a cGMP by cultured immature porcine granulosa
      cells were investigated. Exposure of granulosa cells to gonadotropins and
      follicular fluid resulted in increase of progesterone and cGMP formation.
      Follicular fluid had an inhibitory effect on cAMP synthesis. The findings suggest
      a possible intermediary role of cGMP for the stimulatory action of follicular
      fluid in the process of luteinization of granulosa cells.

PMID- 8307118
TI  - Effects of THA and physostigmine on spatial navigation and avoidance performance
      in mecamylamine and PCPA-treated rats.
AB  - The present study compares the effects of two cholinesterase inhibitors,
      tetrahydroaminoacridine (THA, 1 and 3 mg/kg) and physostigmine (0.12 and 0.36
      mg/kg), on spatial navigation (water maze, WM) and avoidance (step through
      passive avoidance, PA) performance. THA and physostigmine did not facilitate WM
      or PA performance in control or p-chlorophenylalanine (PCPA)-treated rats. THA at
      3 mg/kg, but not at 1 mg/kg, completely restored the defect in WM and PA
      performance in rats pretreated with 7.5 mg/kg mecamylamine, a centrally active
      nicotinic antagonist. Physostigmine completely restored behavior in WM and PA
      tests at 0.12 and 0.36 mg/kg in mecamylamine-treated rats. In rats pretreated
      with mecamylamine+PCPA, 3 mg/kg THA to some extent restored WM performance but
      had no effect on PA retention. Likewise, physostigmine partially restored WM
      performance but did not facilitate PA retention in mecamylamine+PCPA-pretreated
      rats. The present study suggests that serotonergic dysfunction may decrease the
      efficacy of cholinesterase inhibitors to reverse the defect in WM and PA behavior
      occurring as a consequence of a decrease in activity of nicotinic-mediated
      functions.

PMID- 8307117
TI  - Nerve resuturation decreases autotomy in the rat.
AB  - Effects of different kinds of nerve lesions on denervation-induced self
      mutilation (autotomy) was studied in the rat. Four different types of lesion were
      used: nerve transection, nerve transection combined with ligation and extirpation
      of the distal part of the transected nerve, nerve resuturation with a
      microsurgical technique, and lidocaine treatment after transection but before and
      during nerve resuturation. To determine the degree of nerve regeneration, the
      extensor muscles of the ankle joint were prepared and weighed after the follow-up
      period. If the transected nerves were resutured the incidence and severity of
      autotomy decreased significantly when compared to the transection+ligation
      treated rats. The pretreatment with lidocaine did not further decrease the
      autotomy behavior of the rats whose nerves were resutured. In those rats who
      performed autotomy the early onset of self-mutilation correlated positively with
      a moderate, but not high or low, degree of restoration of the muscle weight. The
      present results suggest that autotomy can be decreased with good surgical
      techniques after nerve resuturation.

PMID- 8307119
TI  - Behavioral effects of SI versus SII cortex ablations on tactile orientation
      localization and postural reflexes of rats.
AB  - Ten rats were observed, before and after selective unilateral ablation of the SI
      and/or SII cortical area, for the ability to turn toward tactile stimuli to head,
      limbs, or trunk. Placing and hopping postural reflexes were also observed. SI
      damage caused greater contralateral deficits than SII damage in all these
      behavioral measures; combined ablation of SI plus SII caused the greatest
      contralateral deficits in all measures. Partial recovery of all behaviors was
      observed during six postoperative test sessions, spanning 2 months. In contrast
      to these rats, cats studied in earlier experiments in this laboratory had shown a
      double dissociation, with SI damage followed by contralateral deficits in posture
      and movement but not passive touch, and damage to SII plus subjacent cortex by
      contralateral deficits in passive touch but only very small deficits in posture
      and movement. In other species comparisons, normal rats oriented as vigorously as
      do cats to tactile cues and, like cats, showed tactile responsiveness in
      orientation-localization greater rostrally than caudally. In both species wrong
      way orientations were occasionally observed during the early postoperative period
      following the largest unilateral lesions. Unoperated albino rats oriented much
      less readily than do unoperated cats toward appetitive auditory or visual cues
      signaling availability of food. An accompanying theoretical review paper further
      examines the nature of passive and active touch in terms of these and other
      comparative findings.

PMID- 8307120
TI  - Behavioral specializations of SI and SII cortex: a comparative examination of the
      neural logic of touch in rats, cats, and other mammals.
AB  - In what ways do passive touch and active touch require particular properties of
      cortical physiology? Because it is not easy to make predictions "bottom up" from
      neurophysiology and anatomy to behavior, there have been surprises in studying
      behavioral deficits following selective ablations of SI versus SII. For example,
      in earlier research on cats, unilateral ablation of SI unexpectedly had no effect
      on passive touch but did cause contralateral losses in posture and movement; it
      was ablation of SII plus subjacent cortex that led to contralateral losses in
      passive touch. In contrast, in a recent experiment with rats unilateral ablation
      of either SI or SII caused contralateral losses both in touch and postural
      reflexes. Some of the literature on dogs, monkeys, and humans suggests
      similarities with cats. To better understand these comparative findings, the
      following theoretical factors are considered: the degree of diffuseness versus
      specificity in brain input-output relations demanded or permitted by a behavior,
      the spatial and temporal scales of a behavior, the species' degree of
      encephalization, the need for stimulus generalization or functional equivalence
      of movements, and the relative sizes and sensitivities of different parts of the
      body. Hypotheses are also offered about why the evolution in rats of shortened
      forelimbs and increased vibrissal function may have entailed a peculiar
      compromise between active and passive touch and between functions of SI and SII.

PMID- 8307121
TI  - Vitamin E prevents the place learning deficit and the cholinergic hypofunction
      induced by AF64A.
AB  - The present study examined whether pretreatment with vitamin E would attenuate
      the place learning impairment and the neurochemical deficits induced by
      intracerebroventricular (icv) injection of the cholinotoxin ethylcholine mustard
      aziridinium ion (AF64A). Male Sprague-Dawley rats were pretreated by
      intramuscular injection of either vitamin E or saline 24 h and 15 min prior to
      surgery. They were then infused bilaterally into the cerebroventricles with AF64A
      (3 nmol/side) or artificial cerebrospinal fluid (CSF). Following 14 days of
      postoperative recovery, the rats were trained to acquire a place learning task in
      a water maze for two blocks of four trials a day for 5 days. Following the 40th
      trial a probe trial was used to assess memory for the platform location. After
      completion of behavioral testing, hippocampal high-affinity choline uptake
      (HAChU) was assessed. The groups which had received either saline or vitamin E
      pretreatment followed by icv injection of CSF did not differ significantly on any
      parameter measured and were therefore pooled as control group. Animals which had
      been pretreated with vitamin E and had received icv injection of AF64A exhibited
      neither significant impairment in water maze performance nor significant decrease
      in HAChU. In contrast, animals which had been pretreated by saline followed by
      icv injection of AF64A were significantly impaired in acquisition of the place
      learning task as well as during the probe trial and had reduced HAChU in the
      hippocampus. These findings indicate that vitamin E may have a neuroprotective
      effect in the septohippocampal cholinergic system.

PMID- 8307122
TI  - Seizure-induced increases in NGF mRNA exhibit different time courses across
      forebrain regions and are biphasic in hippocampus.
AB  - In the present study, in situ hybridization and S1 nuclease protection analyses
      were used to evaluate the temporal and spatial parameters of changes in nerve
      growth factor (NGF) mRNA expression in rat forebrain following hilus lesion
      induced recurrent limbic seizures. Seizure-induced increases in NGF mRNA levels
      were widespread with differences in the temporal parameters of change between
      brain areas. There were two distinct increases in NGF cRNA hybridization in
      dentate gyrus stratum granulosum. Hybridization was increased several-fold by 6 h
      after a seizure-producing hilus lesion (HL), declined to below control values by
      12 h post-HL, and then increased again by 24 h post-HL, or 12 h after the
      termination of seizures. This biphasic increase was corroborated by S1 nuclease
      protection analysis. In entorhinal cortex, cingulate cortex and neocortex NGF
      cRNA hybridization was markedly increased first in layers II/III by 6-12 h post
      HL and progressed to layers V/VI by 24 h post-HL. Striking increases in NGF mRNA
      were detected in the majority of amygdaloid nuclei beginning with the cortical
      nuclei by 12 h postlesion and extending into the more deeply placed nuclei by 24
      h postlesion. Labeling was increased in sparsely distributed neurons in the
      caudate putamen, ventral pallidum, and tenia tecta at 24 h post-HL. In all areas,
      hybridization declined to control values by 48-96 h post-HL. NGF expression was
      not changed in some forebrain regions which normally contain NGF mRNA including
      the diagonal bands of Broca and select thalamic nuclei. These data demonstrate
      that seizures stimulate NGF expression in many different types of neurons.
      Moreover, regional differences in the time courses of induction suggest that
      distinct regulatory mechanisms subserve activity-dependent changes in NGF mRNA
      expression in different neuronal populations.

PMID- 8307123
TI  - Magnetic resonance imaging of neuronal grafts in the primate.
AB  - This preliminary study demonstrates the vital role that magnetic resonance
      imaging plays in the study of neuronal grafts in a nonhuman primate model of
      Huntington's disease. MRI scans were used to accurately locate and
      stereotactically lesion the anterior putamen of an adult rhesus monkey, thereby
      mimicking the anatomical and biochemical changes in Huntington's disease. Follow
      up scans were utilized to confirm correct placement of the lesion and to
      stereotactically implant primate fetal neuronal tissue precisely into the lesion.
      Additionally, MRI appeared capable of imaging the fetal striatal grafts in rhesus
      monkeys. While the precise cellular composition of growing grafts was not
      identifiable on MRI scans, differentiation between normal, lesioned, and
      engrafted tissue was possible. Correlation of the magnetic resonance images of
      the grafted regions with actual graft tissue in perfused sections of the brain
      was shown. The use of magnetic resonance imaging, as indicated in these neuronal
      implantation studies, allows for a wide variety of future research possibilities
      where noninvasive and precise localization of the graft is mandated.

PMID- 8307124
TI  - Role of norepinephrine in forebrain and brainstem seizures: chemical lesioning of
      locus ceruleus with DSP4.
AB  - The role of norepinephrine in regulating brainstem seizures has been well
      documented. These seizures are characterized by running/bouncing clonus and tonic
      extensor convulsions. Evidence for noradrenergic regulation of brainstem seizures
      comes partially from studies with genetic models of epilepsy which are
      characterized by innate noradrenergic deficits and from selective lesioning of
      noradrenergic neurons and/or pathways. The present study was conducted to
      evaluate whether destruction of the noradrenergic system using DSP4 (N-(2
      chloroethyl)-N-2-bromobenzylamine) influences forebrain seizure severity.
      Accordingly, 90 female Sprague-Dawley rats (49-55 days old) received DSP4 (50
      mg/kg ip) after a pretreatment of desipramine (a norepinephrine reuptake
      inhibitor), fluoxetine (a serotonin reuptake inhibitor), or saline. A control
      group of 30 animals received two administrations of saline. Three weeks later,
      these animals were tested for facial and forelimb clonus (FFC) threshold
      (convulsive current50; CC50) via corneal electroshock stimulation. The FFC CC50
      thresholds in the animals treated with saline plus DSP4 were significantly
      reduced compared to control (vehicle-vehicle) values. Also, desipramine
      pretreatment, which partially protected the noradrenergic system from the
      neurotoxicity of DSP4, completely obviated the reduction in FFC thresholds. A
      subsequent evaluation of brainstem seizure response using maximal electroshock
      through earclip electrodes confirmed the noradrenergic influence on brainstem
      seizure regulation. These observations provide additional support for a
      noradrenergic role in forebrain as well as brainstem seizure regulation.

PMID- 8307125
TI  - On the role of enkephalin cotransmission in the GABAergic striatal efferents to
      the globus pallidus.
AB  - In the MPTP-treated primate model of Parkinson's disease, loss of dopaminergic
      afferents to the striatum leads to increased activity in striatal efferents to
      the external segment of the globus pallidus. This pathway utilizes both GABA and
      enkephalin as cotransmitters. Little is known regarding either the role of this
      cotransmission in the generation of parkinsonian symptoms or of the nature of any
      functional interaction between GABA and enkephalin. We have investigated the
      roles played by enkephalin and GABA in mediating parkinsonian symptoms by
      injection the GABAA antagonist bicuculline and the broad spectrum opioid
      antagonist naloxone directly into the globus pallidus in the reserpine-treated
      rat model of parkinsonism. Injections of bicuculline, but not naloxone, had
      marked antiparkinsonian effects. However, naloxone attenuated the
      antiparkinsonian effects of bicuculline. We interpret these findings as
      suggesting that increased GABAergic transmission in the globus pallidus is
      responsible for the generation of parkinsonian symptoms in the reserpine-treated
      rat. However, overactive enkephalinergic transmission is not responsible for the
      generation of symptoms and appears to act to reduce the effects of increased
      GABAergic transmission. In complementary studies in vitro, we have demonstrated a
      potential mechanism for this negative interaction. Met-enkephalin (3-10 microM)
      reduced depolarization-evoked release of GABA from terminals in slices prepared
      from rat globus pallidus (IC50, 0.38 microM). A better comprehension of the
      mechanisms by which enkephalin and other peptides modulate the action of amino
      acid transmitters in the basal ganglia is critical to the understanding of the
      neural processes underlying basal ganglia function and movement disorders.

PMID- 8307126
TI  - Neural substrate of a cerebellar movement disorder induced by
      intracerebroventricular injection of propidium iodide in the rat: a Fos
      immunocytochemical study.
AB  - Intracerebroventricular (icv) injection of propidium iodide (PI) in the rat
      results in a transient movement disorder characterized by nystagmus, ataxia, and
      shaking. In the present study we used c-Fos as a marker for neuronal activation
      to investigate the neural substrate underlying this movement disorder. PI was
      injected into the lateral cerebral ventricle of freely moving rats through a
      previously implanted cannula. Animals were perfused 3 h after the injection and
      the brains were processed for c-Fos immunocytochemistry. Paired control animals
      were injected with saline. After PI injection, a significant Fos expression was
      seen in the cerebral cortex, thalamic midline nuclei, thalamic intralaminar
      nuclei, hypothalamus, central gray, pontine nuclei, locus coeruleus, vestibular
      complex, inferior olive, ventrolateral medulla, nucleus of solitary tract, and
      deep cerebellar nuclei. Few or no Fos immunoreactive cells were seen in the above
      structures of the control animals. The present study indicates that a large
      number of neurons located in many different neural structures are activated
      following icv injection of PI. Second, consistent with the cerebellar feature of
      the movement disorder, a major Fos expression was found in the cerebellar
      circuitry (deep cerebellar nuclei, pontine nuclei, vestibular complex, and
      inferior olive). It reinforces further the assumption that the movement disorder
      is due to cerebellar dysfunction caused by PI.

PMID- 8307127
TI  - Consequences of spinal cord injury during the neonatal period on micturition
      reflexes in the rat.
AB  - This study examined the changes in micturition reflexes following spinal cord
      transection in neonatal rats to determine: (1) whether injury to the immature
      nervous system allows greater recovery of function than injury in adult animals
      and (2) whether the management of the lower urinary tract during the initial
      period following spinal injury influences the subsequent recovery of function. In
      one experiment, bladder-to-bladder reflexes in decerebrate neonatal rats (Day 15
      Day 26) were tested 5-11 days after T8-T10 spinalization. While there was no
      difference in the amplitude and duration of reflex bladder contractions or
      bladder capacity between these pups and their nonspinalized controls, the
      spinalized pups exhibited incomplete voiding and an uncoordinated urethral
      sphincter (bladder/sphincter dyssynergia). It is concluded that the dyssynergia
      is inherent to the spinal micturition reflexes and is not due to an initial
      period of bladder areflexia and overdistension since in both the control and
      spinalized neonates micturition is initiated by a somatobladder reflex triggered
      when the mother licks the perineum. A second experiment tested whether neonatal
      spinal cord injury led to improved bladder function in adulthood. Postnatal Day 1
      rat pups were spinalized at T8-T10 and returned to their mothers for the
      remainder of the neonatal period, and their bladder reflexes were tested 4-6
      months later under urethane anesthesia. These rats showed the same lower urinary
      tract dysfunctions (bladder/sphincter dyssynergia, high residual volumes,
      decreased percentage voided volumes, and large-amplitude, long-duration bladder
      contractions) as adult rats that were spinalized as adults.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8307128
TI  - Elevation and clearance of extracellular K+ following graded contusion of the rat
      spinal cord.
AB  - The elevation and clearance of extracellular potassium concentration ([K+]e) were
      studied following graded contusion injury of the rat thoracic spinal cord.
      Animals were anesthetized, paralyzed, laminectomized at T9-T10, and then
      artificially ventilated. A 10-g rod was dropped 1.25, 2.5, or 5 cm onto the
      dorsal thoracic cord with the dura intact. After impact, and incision of the dura
      arachnoid and pial membranes, double-barreled, potassium-selective
      microelectrodes were inserted midway between the midline and lateral edge of the
      cord. For all three injury levels, the elevation of [K+]e was greatest within the
      first 1000 microns from the dorsal surface. In 50 g-cm injuries, increasing [K+]e
      was sometimes observed between 250 and 1000 microns; however such gradients were
      not typically observed in 25 and 12.5 g-cm injuries. Measured at 3-7 min after
      injury, the mean peak elevations of [K+]e were significantly different, measuring
      13 +/- 2.4, 27 +/- 5.5, and 44 +/- 4.2 mM following 12.5, 25, and 50 g-cm
      contusions, respectively. The exponential half-times of [K+]e clearance averaged
      5.8 +/- 1.0, 9.2 +/- 1.8, and 17 +/- 5.7 min for the same respective injury
      levels. These results indicate that elevation of [K+]e following traumatic injury
      to the spinal cord is a graded phenomenon, dependent on the energy of impact.
      This finding is consistent with a mechanism in which simple mechanical injury of
      cell membranes is the proximate cause of potassium release.

PMID- 8307129
TI  - Differential effect of serum on laminin-dependent outgrowth of embryonic and
      adult mouse optic axons in vitro.
AB  - Laminin is an extracellular matrix molecule which promotes neurite outgrowth from
      a variety of neurons in culture. However, the reported effectiveness of laminin
      on neurite outgrowth from retinal ganglion cells in rat and that from chick have
      been contradictory. In chick, embryonic retinal ganglion cells show strong
      laminin-dependent neurite outgrowth which is lost during development. In
      contrast, in rat, laminin promotes neurite outgrowth from adult, but not
      embryonic retinal ganglion cells. We have reexamined the response of adult and
      embryonic mouse retinal ganglion cells to laminin in culture. We found, first,
      that both adult and embryonic retinal neurites respond to laminin with neurite
      outgrowth in serum-free medium. Second, we found that the addition of serum to
      the medium greatly inhibits the outgrowth of neurites from embryonic, but not
      adult, retinal explants. This inhibition appears specific for neurite outgrowth
      involving laminin receptors, since embryonic explants showed extensive neurite
      outgrowth in the presence of serum when astrocytes were used as a substrate.
      These developmental differences in the effect of serum on laminin-dependent
      neurite outgrowth may indicate maturational changes in surface molecules on optic
      fibers related to regenerative failure in the adult CNS.

PMID- 8307130
TI  - Presentation of the rifle project risk factors and life expectancy. The RIFLE
      Research Group.
AB  - Plans are presented for conducting an epidemiological observational project which
      will pool the data from nine Italian field studies covering over 70,000 men and
      women aged 20 to 69 years, belonging to 52 population samples distributed in 13
      different regions of the country. The main objective is to produce multivariate
      models for the prediction of all-cause mortality, life expectancy and selected
      causes of death as a function of some baseline characteristics. The entry
      examinations of the population samples were performed between 1978 and 1987 with
      the measurements of risk factors and other personal characteristics mainly
      related to cardiovascular diseases and other chronic conditions. They include a
      large number of anthropometric, social, biochemical, biophysical, clinical,
      nutritional and behavioural measurements, although only a limited subset of them
      is common to all the studies. The collection of data on life status, mortality
      and causes of death has already been completed for 45 out of the 52 samples,
      although for lengths of follow-up varying from 4 to 12 years. The systematic
      analysis of this data bank will be started in 1993.

PMID- 8307131
TI  - Snoring, sympathetic activity and cardiovascular risk factors in a 70 year old
      population.
AB  - In order to describe the relation between snoring, cardiovascular risk factors,
      metabolic factors and sympathetitic activity, 804 70-year-old males and females
      were classified according to snoring habits and life-style factors (alcohol and
      tobacco consumption), blood pressure, body mass index (BMI), plasma lipids
      (triglycerides, cholesterol, high density lipoprotein), plasma catecholamines
      (epinephrine, norepinephrine), fasting blood glucose and glucose tolerance test
      (1 gram glucose per kg body weight given and blood glucose was measured 1 and 2
      hours thereafter) were evaluated in all participants. Self-reported snoring was
      associated with gender (males showed higher prevalence than females, p < 0.05),
      alcohol consumption (p < 0.01), BMI (p < 0.001), systolic (p < 0.01) and
      diastolic (p < 0.05) blood pressure, glucose tolerance test (p < 0.01), plasma
      norepinephrine (p < 0.05) and partly with tobacco consumption (p = 0.08). No
      associations were found between snoring and fasting glucose, plasma lipids,
      plasma epinephrine or in the use of antihypertensive medication. In multivariate
      analysis, with forced entry of gender, BMI, physical activity, alcohol and
      tobacco consumption, the relation between snoring and blood pressure ceased; only
      systolic blood pressure was associated with snoring (p < 0.05). Snoring was still
      associated with plasma norepinephrine (p < 0.001) and abnormal glucose tolerance
      (p < 0.001). We conclude that, in a 70-year-old population, snoring is associated
      with gender, BMI and alcohol consumption. Snores showed higher plasma
      norepinephrine and abnormal glucose tolerance.

PMID- 8307132
TI  - First characterization in Italy of clinical isolates of mutans streptococci by
      using specific monoclonal antibodies.
AB  - The aim of this investigation was to gain further insight into the prevalence of
      different serotypes of mutans streptococci in the Italian population by using
      specific monoclonal antibodies in an enzyme immunoassay. Isolates from dental
      plaque samples, collected from an adult population living in Pisa (Italy), were
      identified as mutans streptococci on the basis of their morphological and
      biochemical properties, and were then serotyped. The results show that 77.5% of
      the strains isolated belonged to serotype c or f (i.e., S. mutans), 15.9% were
      serotype e (i.e., S. mutans) and only two strains (1.4%) belonged to serotype g
      (i.e., S. sobrinus). These data are partially in agreement with other studies in
      Europe and in the U.S.A. The distribution pattern of the various serotypes turned
      out to be substantially similar among the different groups of patients,
      subdivided on the basis of their caries status, indicating that none of the
      serotypes was particularly associated with dental caries.

PMID- 8307133
TI  - Serotypes and colonization factors of enterotoxigenic Escherichia coli isolated
      in various countries.
AB  - One hundred and six enterotoxigenic E. coli (ETEC) isolated from many
      geographical areas were serotyped and investigated for the presence of
      colonization factor antigens CFA/I and CFA/II, the expression of mannose
      resistant haemagglutination (MRHA) and the levels of surface hydrophobicity.
      CFA/I was found in 6 (17%) of 36 LT+STa+ strains and in 15 (54%) of 28 STa+
      strains; CFA/II was found in 16 (44%) of 36 LT+STa+ strains. None of 42 LT+
      strains showed CFA/I or CFA/II. CFA/I was found in ETEC of serotypes O63:K-:H-,
      O78:K80, O128:K67 and O153:K:H45, whereas CFA/II was found in serotypes O6:H-,
      O6:K15:H16 and O6:K?:H40. Of the 69 CFA/I- CFA/II- ETEC strains, 9 (13%) showed
      MRHA with some of the seven erythrocyte species used and 21 (30%) were
      hydrophobic. Among the 21 hydrophobic strains CFA-negative we have detected: (i)
      6 LT+ strains of serogroup O25 negative for MRHA, (ii) 5 strains O159 (4 LT+ and
      1 LT+ STa+) also negative for MRHA, and (iii) 3 STa+ strains of serotype O27:K
      :H7 that haemagglutinated calf and sheep erythrocytes when grown on Minca-Is. The
      106 ETEC strains belonged to 20 different O serogroups. However, 77 (73%) were of
      one of nine serogroups (O6, O8, O25, O27, O78, O148, O153, O159 and O167). E.
      coli strains belonging to O6 and O153 groups predominated among ETEC isolated in
      Spain, O159 strains in the Central African Republic, O25 and O148 strains in
      Japan, and O15 and O78 strains in India.

PMID- 8307134
TI  - Serum LP(A) levels in randomized healthy men from different European countries.
AB  - Serum lipoprotein(a) [Lp(a)], blood lipids, serum insulin and anthropometric
      parameters were determined in randomized samples of 38-year-old men living in six
      European cities: Ede (The Netherlands), Deinze (Belgium), Warsaw (Poland), Lumiar
      (Portugal), Verona and Naples (respectively in northern and in southern Italy).
      In total, 406 healthy men were studied. Serum Lp(a), blood lipids and serum
      insulin were measured in one laboratory. All the anthropometric and metabolic
      variables considered were statistically different among the participating sites,
      with the exception of Lp(a) serum levels. In spite of the lack of overall
      significant inter-center differences (Kruskal-Wallis test), the subjects from the
      two Italian cities had significantly lower Lp(a) serum levels than the subjects
      from Belgium and Portugal (Mann-Whitney U test, p < 0.01). In all cities the
      distribution of serum Lp(a) levels were highly skewed; the percentage of subjects
      with serum Lp(a) levels higher than 30 mg/dl (i.e., the commonly accepted risk
      level of cardiovascular disease) was 6% in both Verona and Naples (Italy), 12% in
      The Netherlands, 16% in Poland, 18% in Belgium and 19% in Portugal (for the last
      two cities, respectively, p < 0.02 and p < 0.01 vs Italian cities, chi-square
      test). Neither anthropometric (body mass index, waist/hip circumference ratio)
      nor metabolic (serum lipids and insulin) parameters showed any significant
      relationship with serum Lp(a) levels in any of the sites (Spearman's rank
      correlation). These data support the possibility of a difference in serum Lp(a)
      levels among different European countries.

PMID- 8307135
TI  - Nosocomial infection in surgery wards: a controlled study of increased duration
      of hospital stays and direct cost of hospitalization.
AB  - Excess length of hospital stays and associated costs were assessed in patients
      hospitalized in the department of general and digestive surgery who acquired
      nosocomial infections. A prospective study of matched infected-uninfected
      patients nested in a cohort was used to estimate the length of the hospital stay
      of infected patients. Matched controls were obtained with respect to patient
      exact primary diagnosis, operative procedure and classification, age and, if
      possible, underlying disease, elective or emergency procedure and invasive
      devices. Superficial surgical wound infection prolonged the average hospital stay
      of the nosocomially infected patient by an average of 12.6 days, wound infection
      (deep and superficial) by 14.3 days and infections other than wound infection by
      7.3 days as compared to the uninfected matched controls.

PMID- 8307136
TI  - A community survey on maternal and child health services utilization in rural
      Ethiopia.
AB  - A household health interview survey on MCH services utilization was carried out
      in 22 villages of a rural district of Arsi region, Ethiopia, before the launching
      of an integrated MCH programme. Coverage of antenatal services was 26%, and 61%
      of the women who received antenatal care reported having had 3 or more visits.
      Antenatal care was positively associated with living within 10 km of the Health
      Centre. Twenty-eight percent of the mothers attended the under-5 clinic and most
      returned for 3 or more visits. In addition, 99% reported having breast-fed their
      last child but more than 25% started weaning only after the seventh month of age.
      Differences in practice of treating diarrhoea according to knowledge of ORS were
      found. Of the 33% of those with knowledge of ORS, almost 90% reported use of ORS
      for treating child's diarrhoea, showing a positive attitude towards modern health
      care. The proportion of women using family planning was 5%, with no difference
      found between Christians and Muslims. Results on EPI coverage validated data from
      routine reporting. Integration of MCH services including out-reach activities may
      increase access and coverage of MCH services.

PMID- 8307137
TI  - Parental smoking and other risk factors for wheezing bronchitis in children.
AB  - A population-based case-control study was performed to investigate etiologic
      factors for wheezing bronchitis and asthma in children up to four years of age. A
      total of 199 children hospitalized for the first time with these diagnoses at a
      major hospital in Stockholm in 1986-1988 constituted the cases, 351 children from
      the catchment area of the hospital were used as controls. Information on known
      and suspected risk factors was obtained through home interviews with a parent.
      Parental smoking was associated with a relative risk of 1.8 (95% confidence
      interval 1.3-2.6) corresponding to a population attributable proportion of 27%.
      The strongest association was seen for maternal smoking and children below 18
      months of age. Other major risk factors included atopic heredity, recurrent upper
      respiratory tract infections and breast-feeding less than 3 months, which
      appeared to interact multiplicatively with parental smoking. The environmental
      factors had a stronger influence in the youngest age group, and the overall
      attributable proportion associated with parental smoking, short breast-feeding
      period and exposure to pets in the household was 43%. It is clear that successful
      primary prevention could dramatically reduce the incidence of wheezing bronchitis
      in children.

PMID- 8307138
TI  - Inter-cohort differences in coronary heart disease mortality in the 25-year
      follow-up of the seven countries study.
AB  - Sixteen cohorts of men aged 40-59 years at entry were examined with the
      measurement of some risk factors and then followed-up for mortality and causes of
      death for 25 years. These cohorts were located in the USA (1 cohort), Finland
      (2), the Netherlands (1), Italy (3), the former Yugoslavia (5), Greece (2), and
      Japan (2), and included a total of 12,763 subjects. Large differences in age
      adjusted coronary heart disease (CHD) death rates were found, with extremes of 45
      per 1000 in 25 years in Tanushimaru, Japan, to 288 per 1000 in 25 years in East
      Finland. In general, higher rates were found in the US and Northern European
      cohorts as compared to the Southern European and Japanese cohorts. However,
      during the last 10 years of follow-up large increases of CHD death rates were
      found in some Yugoslavian areas. Out of 5 measured entry characteristics treated
      as age-adjusted levels (serum cholesterol, systolic blood pressure, cigarette
      smoking, body mass index and physical activity at work), only serum cholesterol
      was significant in explaining cohort differences in CHD death rates. Over 50% of
      the variance in CHD death rates in 25 years was accounted for by the difference
      in mean serum cholesterol. This association tended to decline with increasing
      length of follow-up, but this was due to the great changes in mean serum
      cholesterol in the two Yugoslavian cohorts of Velika Krsna and Zrenjanin. When
      these two cohorts were excluded the association increased with time. Changes in
      mean serum cholesterol between year 0 and 10 helped in explaining differences in
      CHD death rates from year 10 onward. It can be concluded that this study suggests
      that mean serum cholesterol is the major risk factor in explaining cross-cultural
      differences in CHD.

PMID- 8307139
TI  - Prevalence of hepatitis virus infections in Albanian refugees.
AB  - A sample of 393 Albanian refugees, including both children and adults, was tested
      for serological HAV, HBV, HDV and HCV markers. A high prevalence of infection
      with both the hepatitis A and B viruses was found, while HDV and HCV infections
      were uncommon. The overall prevalence of anti-HAV was 96%; it was very high in
      children 0-10 years, suggesting that HAV infection is largely acquired during
      childhood and that poor ambiental conditions influence the spreading of this
      viral infection. One or more serological markers of HBV infection were found in
      295 Albanians (75%), confirming the endemic nature of this virus in the Albanian
      community. The overall prevalence of HBsAg was 19%, and the carrier rate was
      higher in males than in females. The high HBsAg prevalence among children
      suggests that HBV infection is usually acquired in early childhood. The
      serological data obtained in the Albanian sample examined clearly indicate the
      urgent need for measures to reduce the incidence of HAV and HBV infections and to
      avoid the further spread of HDV and HCV infections. Finally, the high prevalence
      of type B hepatitis indicates the necessity of vaccination against HBV for all
      risk groups and for all children at birth.

PMID- 8307140
TI  - Serological comparison of purified antigens 60 and 85A (P32) of Mycobacterium
      bovis BCG, and purified protein derivative, in active pulmonary tuberculosis.
AB  - The immunoglobulin G (IgG) response directed against Mycobacterium bovis BCG
      antigens 60 (A60) and 85A (P32), and purified protein derivative (PPD), was
      investigated in order to compare the serodiagnostic potentials of these antigens
      in tuberculosis (TB). The sera of 59 patients with active minimal or moderately
      advanced pulmonary TB and of 59 healthy control subjects were tested by enzyme
      linked immunosorbent assay. The frequencies of positivity were significantly
      higher (P < 0.001) in patients than in controls and similar with all three
      antigens. The strongest correlation was found between the responses to A60 and
      PPD (P < 0.001), the weakest between the responses to A60 and P32 (P < 0.05).
      Discrepancies were observed in newly diagnosed patients before the institution of
      specific chemotherapy and in patients with negative direct smears at the time of
      diagnosis. Untreated patients with negative direct smears presented the lowest
      sensitivities. P32 was the most effective antigen in diagnosing these cases (50%
      positivity); A60 was not better than PPD (29% and 21% positivity, respectively).
      The results presented here emphasize the importance of comparing antigens with
      the same samples in order to allow their real respective evaluation.

PMID- 8307141
TI  - Flow cytometric indirect immunofluorescence assay with high sensitivity and
      specificity for the detection of antibodies to HSV-1 and HSV-2.
AB  - Cells infected with HSV-1 or HSV-2 develop viral antigens which can be detected
      by immunofluorescence. We developed a flow cytometric indirect immunofluorescence
      assay to detect and quantitate antibodies to HSV-1 and HSV-2 in human sera.
      Results obtained by flow cytometry for detecting antibodies against HSV-1, when
      compared with results obtained by ELISA, showed an index of overall agreement of
      100%. The correlation between the antibody titers obtained with each method was
      found to be highly significant. An index of overall agreement equal to 94.1% was
      observed between results obtained by flow cytometry and by immunofluorescence as
      concerns the discrimination of HSV-2 positive from negative samples. However, the
      correlation between antibody titers was found to be not statistically
      significant. The flow cytometric assay proved to be type-specific.

PMID- 8307142
TI  - In vitro susceptibility of mycelial and yeast forms of Penicillium marneffei to
      amphotericin B, fluconazole, 5-fluorocytosine and itraconazole.
AB  - The mycelial (25 degrees C) and yeast-like (37 degrees C) forms of Penicillium
      marneffei clinical and type strains were investigated for their in vitro
      susceptibility to amphotericin B (AmB), 5-fluorocytosine (5-FC), fluconazole
      (FLU) and itraconazole (ITZ), using Bacto antibiotic medium 3, yeast-nitrogen,
      Sabouraud's dextrose (pH 5.7) and high resolution (pH 7.1) broth media
      (1ml/tube), respectively. Results indicated that the minimal inhibitory and
      minimal fungicidal concentrations (MICs and MFCs) for the mycelial cultures of P.
      marneffei to AmB were in the range 0.78-1.56 and 0.78-3.125 micrograms/ml,
      respectively, as against 3.125-25 micrograms (MICs) for the yeast form cultures.
      The MFCs to AmB for the yeast form were one dilution higher. The MICs to FLU were
      generally lower for the yeast form (6.25-25 micrograms) than the mycelial form
      (25-50 micrograms/ml), whereas MFCs for the mycelial cultures were > 100
      micrograms as compared to 6.25-100 micrograms for their yeast form. The MICs for
      the mycelial form to 5-FC ranged from < 0.195-0.39 microgram. Higher MICs (6.25
      micrograms) were recorded for their yeast form. The MFCs to 5-FC for the yeast
      form were 25-100 micrograms/ml. The MICs for the mycelial form to ITZ ranged from
      < 0.195 to 3.125 micrograms/ml. Higher values (< 0.195-50 micrograms) were
      recorded for their yeast-like form. The MFCs to ITZ for mycelial and yeast forms
      ranged from < 0.195-0.39 and 25-100 micrograms/ml, respectively. Results indicate
      that P. marneffei's yeast form is more sensitive to FLU and ITZ (8 of 10 strains)
      while the mycelial form displayed greater susceptibility to AmB and 5-FC. The
      MICs for ITZ remained steady in SD medium, pH 5.7 to 7.1. However, some strains
      gave higher MIC values (0.39-1.56 micrograms/ml) when tested in the HR.

PMID- 8307144
TI  - The early stage of the recurrent cholera epidemic in Luanda, Angola.
AB  - The recurrent cholera epidemic in Angola has been occurring in the rainy hot
      season since 1987. About 350 cases were registered in the Luanda province in the
      first quarter of 1992. Out of 110 analysed cases, 13 were positive for V.
      parahaemolyticus and 57 were positive for multiresistant V. cholerae O1. Such
      strains were also isolated in the Bengo river, which feeds the Luanda water
      supply.

PMID- 8307143
TI  - Antibiotic susceptibility and phage typing of methicillin-resistant
      Staphylococcus aureus clinical isolates from blood cultures of 692 patients in 15
      Israeli hospitals.
AB  - Six hundred ninety-two clinical isolates of Staphylococcus aureus were collected
      from blood cultures of 692 patients in 15 Israeli hospitals over a two year
      period. Antibiotic sensitivity was tested by the standard disk diffusion
      technique. Of these isolates, 41.6% were methicillin-resistant (MRSA). All 288
      MRSA isolates were sensitive to vancomycin and pristinomycin; 98.6% were
      sensitive to fucidine; 97.9% to imipenem; 79% to rifampicin; 63.6% to amikacin;
      54.5% to augmentin; 36.4% to clindamycin; 12.6% to ciprofloxacin; 11.9% to
      cotrimoxazole and ofloxacin; 10.5% to gentamicin; 9.8% to erythromycin; and 8.4%
      to norfloxacin. Phage typing was determined by using the international set of
      phages. All the isolates that were sensitive to Group I phages, and 91.8% of
      those sensitive to Group II phages, were sensitive to methicillin. Of the
      isolates that were sensitive to Group III phages, 79.2% were methicillin
      resistant and 72.4% of the latter were sensitive to phages 75/85. Of the isolates
      that were sensitive to Group III and miscellaneous phages, 50.7% were methicillin
      resistant and 71% of the latter were sensitive to phages 75/85 as well.

PMID- 8307145
TI  - Prevalence and incidence of hepatitis C virus infection among male prison inmates
      in Maryland.
AB  - To identify incidence of antibody to hepatitis C virus among 265 male prison
      inmates, we assayed paired serum specimens obtained at intake in 1985-1986 with
      follow-up specimens in 1987. Intake prevalence was 38 percent. Seroincidence was
      1.1/100 person years in prison. This finding might reflect saturation of high
      risk subgroups or possibly reduced frequency of exposures following
      incarceration.

PMID- 8307146
TI  - Molecular cloning of a murine N-type calcium channel alpha 1 subunit. Evidence
      for isoforms, brain distribution, and chromosomal localization.
AB  - A cDNA encoding a N-type Ca2+ channel has been cloned from the murine
      neuroblastoma cell line N1A103. The open reading frame encodes a protein of 2,289
      amino acids (257 kDa). Analysis of different clones provided evidence for the
      existence of distinct isoforms of N-type channels. High levels of mRNA were found
      in the pyramidal cell layers CA1, CA2 and CA3 of the hippocampus, in the dentate
      gyrus, in the cortex layers 2 and 4, in the subiculum and the habenula. The N
      type Ca2+ channel gene has been localized on the chromosome 2, band A.

PMID- 8307147
TI  - Cloning and characterization of the cDNA encoding rice elongation factor 1 beta.
AB  - We have cloned and sequenced a cDNA coding for rice elongation factor 1 beta (EF
      1 beta). The clone was 1420 bp long and contained an open reading frame coding
      for 229 amino acids. The overall identity between rice EF-1 beta and rice EF-1
      beta' [Matsumoto, S., Oizumi, N., Taira, H. and Ejiri, S. (1992) FEBS Lett. 311,
      46-48] is 60% at the amino acid sequence level; a higher percent identical
      residues (81%) were especially observed in the C-terminal region. Rice EF-1 beta
      has no conserved phosphorylation site for casein kinase II and no leucine zipper
      motif, although these motifs are well conserved in EF-1 delta (= beta in plants)
      subunits of animal EF-1.

PMID- 8307148
TI  - Cloning and functional expression of a cardiac inward rectifier K+ channel.
AB  - We have isolated a cDNA coding for an inward rectifier K+ channel (RBHIK1) from
      rabbit heart. The cloned cDNA encodes a protein of 427 amino acids with two
      putative transmembrane segments. The primary structure of RBHIK1 is highly
      homologous to that of IRK1 which is an inward rectifier K+ channel recently
      cloned from mouse macrophage by expression cloning. When expressed in Xenopus
      oocytes, RBHIK1 current showed strong inward rectification and was inhibited by
      extracellular Ba2+ and Cs+. RNA blot analysis revealed the expression of RBHIK1
      mRNA in various rabbit tissues, especially high level in the ventricular muscle.

PMID- 8307149
TI  - Solvent and thermal denaturation of the acidic compact state of apomyoglobin.
AB  - The stability of the acidic compact state of apomyoglobin toward the denaturant
      action of guanidinium hydrochloride and temperature was studied by examining the
      effects induced on the intrinsic tryptophanyl fluorescence and that of the adduct
      formed with 1,8-anilinonaphthalenesulfonate (ANS). The results indicated that the
      disorganization of tryptophanyl environments is caused by a cooperative discrete
      molecular transition, thus contrasting the assumption that the acidic compact
      form of apomyoglobin might be a molten globule state. The unfolding of the ANS
      binding regions was found to involve, at least, two stages over a wide range of
      denaturant concentrations.

PMID- 8307150
TI  - Cloning and functional expression of a tetrabenazine sensitive vesicular
      monoamine transporter from bovine chromaffin granules.
AB  - Using oligonucleotide primers derived from the vesicular monoamine transporters
      sequences, a cDNA predicted to encode the bovine chromaffin granule amine
      transporter has been cloned (b-VMAT2). Surprisingly, its structure is more
      similar to the rat brain transporter (VMAT2), than to the rat adrenal counterpart
      (VMAT1). Unlike rat VMAT1, bovine VMAT2 appears to be expressed both in the
      adrenal medulla and the brain, as judged by Northern analysis. After
      modification/deletion of the seven amino acids at the N-terminus of the protein
      it was expressed in a functional form. The order of affinity of the bovine VMAT2
      transporter to substrates is: serotonin > dopamine = norepinephrine >
      epinephrine. Also, the recombinant bovine adrenal transporter is highly sensitive
      to tetrabenazine, in sharp contrast to the rat adrenal transporter. The findings
      indicate, therefore, a clear species variation in which structure and function of
      the bovine adrenal transporter resemble the rat brain protein, while its tissue
      distribution is distinct from both types of rat proteins. In addition, the
      predicted protein sequence is identical to the experimentally determined N
      terminus sequence of the purified vesicular amine transporter [Stern-Bach et al.
      (1992) Proc. Natl. Acad. Sci. USA 89, 9730-9733].

PMID- 8307151
TI  - A high-conductance voltage-dependent multistate Ca2+ channel found in sea urchin
      and mouse spermatozoa.
AB  - Ion fluxes through poorly understood channel-mediated mechanisms participate in
      the interaction between spermatozoa and egg. Previously, we reported the
      characterization in planar bilayers of a high conductance Ca(2+)-selective,
      voltage-dependent multistate channel from S. purpuratus sea urchin sperm plasma
      membranes. Here we show that this ion channel can be directly transferred to
      planar lipid bilayers upon sperm addition, from sea urchin (S. purpuratus and L.
      pictus) and from mouse. We found that spermatozoa from these species possess a
      conspicuous Ca(2+)-selective, high conductance, multi-state, voltage-dependent
      channel, which displays similar voltage dependence and equal PBa2+/PK+
      approximately 4 in the three species. The presence of this Ca2+ channel in such
      diverse species suggests it plays a relevant role in sperm physiology. The high
      sensitivity of planar bilayers to detect single ion channels can now be used to
      study ion channel regulation and gamete interaction.

PMID- 8307152
TI  - The interleukin-1-stimulated protein kinase that phosphorylates heat shock
      protein hsp27 is activated by MAP kinase.
AB  - In KB cells, interleukin-1 (IL-1), epidermal growth factor and phorbol ester
      transiently activated both MAP kinase and a serine kinase which phosphorylated
      the heat shock protein hsp27. Extracts made from IL-1-stimulated KB cells
      phosphorylated recombinant hsp27, in vitro, on serine residues 78 and 82 which
      are contained within Arg-X-X-Ser motifs similar to those phosphorylated by the
      ribosomal protein S6 kinases. Upon size exclusion chromatography, however, hsp27
      kinase eluted as a single peak of activity at 50-60 kDa, clearly separated from
      ribosomal protein S6 kinases. Treatment of partially purified hsp27 kinase with
      protein phosphatase-2a reduced its activity by 80%. De-phosphorylated hsp27
      kinase could be approximately 50% reactivated by a factor present in IL-1-treated
      cell extracts in the presence of ATP. This factor co-eluted with MAP kinase after
      partial purification by DEAE-cellulose, phenyl Sepharose, and size exclusion
      chromatography. Purified sea star p44mpk and recombinant ERK2 MAP kinases were
      also capable of re-activating hsp27 kinase to a similar extent. These data
      suggest that hsp27 kinase is downstream from, and probably a direct target of MAP
      kinase.

PMID- 8307153
TI  - The alpha-isoform of glycogen synthase kinase-3 from rabbit skeletal muscle is
      inactivated by p70 S6 kinase or MAP kinase-activated protein kinase-1 in vitro.
AB  - The alpha-isoform of glycogen synthase kinase-3 (GSK3 alpha) was inactivated by
      80% towards a synthetic peptide substrate upon incubation with Mg-ATP and either
      MAP kinase-activated protein (MAPKAP) kinase-1 or p70 S6 kinase. Inactivation by
      either kinase resulted from the phosphorylation of Ser-21 and was reversed by
      treatment with protein phosphatase 2A1. Phosphorylation also decreased GSK3 alpha
      activity towards glycogen synthase, inhibitor-2 and c-jun. The specificity of
      GSK3 alpha was similar to GSK3 beta, but with the synthetic peptide substrate
      heparin stimulated the dephosphorylated form of GSK3 alpha (6-fold) more than
      GSK3 beta (1.8-fold). After phosphorylation, both isoforms were stimulated 15-20
      fold by heparin.

PMID- 8307154
TI  - Tumor necrosis factor enhances low density lipoprotein oxidative modification by
      monocytes and endothelial cells.
AB  - The effect of tumor necrosis factor on the oxidative modification of LDL by U937
      human monocytes or murine endothelial cells was studied by determination of the
      lipid peroxidation product content and the electrophoretic mobility of the
      particle. In the range of concentrations from 2.5 to 10 ng/ml, the cytokine
      induced a dose-dependent increase in cellular-induced oxidation of LDL. This
      effect was accompanied by a stimulation of LDL degradation by J774 macrophage
      like cells. Concurrently, the TNF-treated cells secreted superoxide anion with a
      higher rate. Since LDL oxidation is believed to be an important feature in the
      formation of the atherosclerotic plaque, the described effects of TNF might be of
      importance in long-term exposure to this cytokine during inflammation.

PMID- 8307155
TI  - Induction of protein-tyrosine phosphatase LC-PTP by IL-2 in human T cells. LC-PTP
      is an early response gene.
AB  - Tyrosine phosphorylation has been implicated in interleukin 2 (IL-2)-induced
      growth signaling and the phosphorylation levels are regulated by the balance of
      tyrosine kinase and tyrosine phosphatase activities. Here, we demonstrate the
      rapid activation of a leukocyte tyrosine phosphatase LC-PTP (HePTP) gene
      expression by IL-2 in an IL-2 dependent human T cell ILT-Mat. Accumulation of LC
      PTP mRNA appeared at 1 h and peaked at 6 h after IL-2 stimulation, simultaneous
      with the G1 to early S phase, and the induction of LC-PTP mRNA did not require
      protein synthesis. LC-PTP protein increased approximately 6-fold at 8 h after IL
      2 stimulation. Nuclear run-on assays showed that the induction of LC-PTP mRNA
      expression is mostly due to transcriptional activation. These data suggest that
      LC-PTP is an early response gene and its protein seems to be a crucial molecule
      which regulates the tyrosine phosphorylation level during T cell proliferation.

PMID- 8307156
TI  - Expression, purification and characterization of a Kunitz-type protease inhibitor
      domain from human amyloid precursor protein homolog.
AB  - The Kunitz-type protease inhibitor domain from a recently identified homolog of
      the Alzheimer amyloid precursor protein (APPH KPI) was expressed in yeast,
      purified and characterized. Its inhibition profile towards several serine
      proteases was studied and compared to that of APP KPI, the Kunitz domain from the
      Alzheimer amyloid precursor protein. APPH KPI was shown to inhibit proteases with
      trypsin-like specificity with an inhibitor profile resembling that of the APP KPI
      domain. The KPI domains from APP and APPH inhibited trypsin (Ki = 0.02 nM), and
      plasma kallikrein (Ki = 86 nM) with approximal equal affinity. In comparison to
      APP KPI (Ki = 82 nM) the KPI domain of the homolog, APPH KPI, (Ki = 8.8 nM) was a
      more potent inhibitor of glandular kallikrein. APPH KPI was a less potent
      inhibitor of chymotrypsin than APP KPI (Ki = 78 nM as compared to Ki = 6 nM),
      plasmin (Ki = 81 nM as compared to 42 nM), and factor XIa (Ki = 14 nM as compared
      to Ki = 0.7 nM). The affinity of factor XIa for APPH KPI is sufficiently high to
      allow for an interaction in the blood. It is, however, well possible that the
      physiological protease ligand for the receptor-like APPH protein has yet to be
      identified.

PMID- 8307157
TI  - Characterisation of the F-actin binding domains of villin: classification of F
      actin binding proteins into two groups according to their binding sites on actin.
AB  - The F-actin binding properties of chicken villin, its headpiece and domains 2-3
      (V2-3) have been analysed to identify sites involved in bundle formation.
      Headpiece and V2-3 bind actin with Kd values of approximately 7 microM and
      approximately 0.3 microM, respectively, at low ionic strength. V2-3 binding, like
      that of villin, is weakened with increasing salt concentration; headpiece binding
      is not. Competition experiments show that headpiece and V2-3 bind to different
      sites on actin, forming the two cross-linking sites of villin. Headpiece does not
      compete with the F-actin binding domains of gelsolin or alpha-actinin, but it
      dissociates actin depolymerizing factor. We suggest that the F-actin binding
      domains of actin severing, crosslinking and capping proteins can be organized
      into two classes.

PMID- 8307158
TI  - Distribution and characterization of immunoreactive adrenomedullin in human
      tissue and plasma.
AB  - A specific and sensitive radioimmunoassay for human adrenomedullin has been
      developed and distribution and characterization of immunoreactive adrenomedullin
      in human tissue were investigated. The radioimmunoassay specifically recognizes
      its carboxyterminal region and half maximal inhibition of binding of
      radioiodinated adrenomedullin(40-52)NH2 was observed at 11 fmol/tube.
      Immunoreactive adrenomedullin was abundant in adrenal medulla (47.7 +/- 26.1
      fmol/mg, mean +/- S.D.) and was ubiquitously found in all tissue examined. The
      mean plasma concentration of adrenomedullin in three normal individuals was 17.2
      +/- 6.4 pg/ml (mean +/- S.D.). By analysis with reverse-phase high-performance
      liquid chromatography coupled with the radioimmunoassay, most immunoreactive
      adrenomedullin in the adrenal medulla, atrium and lung was found to be
      adrenomedullin(1-52)NH2.

PMID- 8307159
TI  - Cloning of the classical guinea pig pancreatic lipase and comparison with the
      lipase related protein 2.
AB  - Starting from total pancreatic mRNAs, the classical guinea pig pancreatic lipase
      was cloned using rapid amplification of 3' and 5' cDNA ends. Internal
      oligonucleotide primers were designed from a partial cDNA clone including the
      region coding for the lid domain. Using this strategy, we did not amplify the
      cDNA corresponding to the pancreatic lipase related protein 2 in which the lid
      domain is deleted. Amino acid sequences of the classical guinea pig pancreatic
      lipase and the related protein 2 were compared based on the primary and tertiary
      structures of the classical human pancreatic lipase. Their distinct physiological
      roles are discussed in the light of functional amino acid differences.

PMID- 8307160
TI  - Isolation and characterization of multiple isoforms of the rat urokinase receptor
      in osteoblasts.
AB  - A rat urokinase receptor (uPAR) cDNA fragment was amplified by RT-PCR from RNA of
      the rat osteoblastic cell line CFK-1. Using this DNA species as a hybridization
      probe two rat uPAR cDNAs were isolated from a CFK-1 cDNA library. These two cDNAs
      encode an identical uPAR protein except for a single base mutation which results
      in the substitution of cysteine to serine at amino acid 71 in one variant. PCR
      analysis of rat genomic DNA revealed the presence of an additional uPAR arising
      from alternate splicing which is expressed in a variety of tissues. These studies
      provide the tools for examining uPAR function in fibrinolysis, tumor invasion and
      metastasis in the rat and for identifying the mechanism of species specificity in
      uPA actions.

PMID- 8307161
TI  - Calcium influx and protein kinase C alpha activation mediate arachidonic acid
      mobilization by the human NK-2 receptor expressed in Chinese hamster ovary cells.
AB  - We have cloned a cDNA encoding the human ileal neurokinin-2 (NK-2) receptor which
      mediates powerful neurokinin A-stimulated arachidonic acid (AA) and prostaglandin
      release when expressed in CHO cells. Two major signal transduction events appear
      to underlie this response. Firstly, AA liberation is critically dependent upon
      agonist-stimulated influx of extracellular Ca2+ although not release from
      intracellular stores. Secondly, NK-2 receptor-linked AA mobilization requires
      concomitant PKC activation and based upon limited subtype immunodetectability as
      well as toxin, identical pretreatment inhibits AA release partially and blocks
      PKC alpha translocation completely. These observations indicate that in this cell
      system AA liberation reflects NK-2 receptor-dependent activation of two distinct
      but converging signal transduction pathways regulated by different G-protein
      species and involving Ca2+ influx and PKC alpha activation.

PMID- 8307162
TI  - Elongation factor-2 kinase: effective inhibition by the novel protein kinase
      inhibitor rottlerin and relative insensitivity towards staurosporine.
AB  - The elongation factor-2 (eEF-2) is selectively phosphorylated by the eEF-2 kinase
      (calmodulin-dependent kinase III). This phosphorylation can be inhibited by
      calmodulin antagonists, such as CGS 9343B (IC50 = 4 microM). The novel protein
      kinase inhibitor rottlerin is shown to suppress eEF-2 phosphorylation with an
      IC50 of 5.3 microM. By contrast, the eEF-2 kinase is rather resistant towards the
      potent but non-selective protein kinase inhibitor staurosporine (IC50 > 50
      microM) and thus can be differentiated from most other protein kinases that are
      suppressed by staurosporine in the nM range.

PMID- 8307163
TI  - Structure and stability of pertussis toxin studied by in situ atomic force
      microscopy.
AB  - Pertussis toxin, both complete and the B-oligomer, were imaged by atomic force
      microscopy (AFM), using specimens prepared by simple surface adsorption on mica
      without further manipulation. The spatial arrangement of the subunits of the B
      oligomer was clearly resolved, representing the first protein quaternary
      structure obtained by AFM in situ. The results suggest that the B-oligomer is a
      flat pentamer with the two large subunits located next to each other, and the
      catalytic A-subunit situated at the center above. We found that the B-pentamer
      was structurally stable for temperatures up to 60 degrees C and within the pH
      range of 4.5-9.5. It is also demonstrated that the AFM was capable of resolving
      features down to 0.5 nm on the B-oligomers, indicating its great potential for
      structural determination.

PMID- 8307164
TI  - Mapping the binding surface of interleukin-8 complexed with an N-terminal
      fragment of the type 1 human interleukin-8 receptor.
AB  - Interleukin-8 and its receptors are key mediators of immune and inflammatory
      responses. Heteronuclear NMR spectroscopy has been utilized to map the binding
      surface on interleukin-8 (IL-8) for an N-terminal fragment of the human Type-1 IL
      8 receptor. A peptide corresponding to residues 1-40 of the IL-8 type 1 receptor
      (IL8-r1) was titrated into a sample of uniformly 15N-labeled IL-8. IL8-r1 binds
      to IL-8 with a dissociation constant of 170 +/- 50 microM assuming the peptide
      binds with a stoichiometry of one peptide per IL-8 monomer, exchanges rapidly (>
      900 s-1) between free and bound states, and selectively perturbs the chemical
      environment of several IL-8 residues. The binding surface on IL-8 suggested by
      our results is comprised of residues in strand beta 3 of the beta-sheet (Glu48 to
      Cys50), the turn preceding beta 3 (Ser44), the C-terminal alpha-helix (Val61) and
      the irregular N-terminal loop region (Thr12, Lys15, Phe17, His18, Lys20 and
      Phe21). The IL-8 dimer appears to present two symmetrical binding surfaces for
      the IL8-r1 peptide, suggesting two receptor peptides may bind per dimer.

PMID- 8307165
TI  - Determination of the molecular mass of the native beta-cell sulfonylurea
      receptor.
AB  - In the present study we have determined the molecular mass of the beta-cell
      sulfonylurea receptor in its native form by two different experimental
      approaches; gel filtration chromatography and radiation inactivation analysis. We
      first confirmed that the denatured photolabelled MIN6 beta-cell receptor had a
      molecular size of 141 +/- 2 kDa (mean +/- S.E., n = 8). Under non-denaturing
      conditions, using gel filtration chromatography, apparent molecular masses of 166
      +/- 1 kDa (mean +/- S.E., n = 3) and 182 +/- 5 kDa (mean +/- S.E., n = 4) were
      determined for the photoaffinity-labelled and unlabelled sulfonylurea receptor,
      respectively. We conclude that in the solubilized state the receptor exists as a
      monomer. Radiation inactivation analysis indicated that the receptor has a target
      size of 250 +/- 30 kDa (mean +/- S.E., n = 7). This value for the molecular mass
      is larger than that obtained from SDS-PAGE following photolabelling of the
      receptor (141 kDa) suggesting that the beta-cell sulfonylurea receptor is
      composed of more than one subunit in the native membrane.

PMID- 8307166
TI  - The GRB2/Sem-5 adaptor protein.
AB  - GRB2/Sem-5 is a 25-kDa adaptor protein which contains a central Src homology type
      2 (SH2) domain flanked by two Src homology type 3 (SH3) domains. GRB2/Sem-5 was
      first identified due to the essential role of the sem-5 gene product in the
      vulval induction pathway in Caenorhabditis elegans. The SH2 domain of GRB2/Sem-5
      binds to a number of tyrosine phosphorylated proteins, most notably the epidermal
      growth factor receptor, the insulin receptor substrate IRS-1 and another putative
      adaptor protein, Shc. The SH3 domains bind to Sos, a guanine nucleotide exchange
      factor for Ras proteins. GRB2/Sem-5 brings together Sos and tyrosine
      phosphoproteins into a complex and thereby may regulate the nucleotide exchange
      rate of Ras and hence its activation state.

PMID- 8307167
TI  - The origin of human immunodeficiency virus type-1 rev gene. An evolutionary
      hypothesis.
AB  - The Rev protein of human immunodeficiency virus type-1 is an RNA-binding
      posttranscriptional transregulator encoded by an accessory gene that is distinct
      from retroviral oncogenes and whose origin is unclear. We hypothesize that the
      rev gene was generated by duplication of a viral RNA segment having a secondary
      structure that evolved into the Rev-responsive element (RRE). This hypothesis is
      based on the following findings. First, accumulated data on functional mapping of
      Rev, Tat, and the transmembrane protein of Env suggested that the major coding
      exon of rev should have been inserted into the transmembrane region of env during
      the course of its evolution. Experiments with equine infectious anemia virus,
      another complex retrovirus, also indicate that a large portion of rev is located
      within the dispensable transmembrane region of env. Second, base usage analysis
      suggests the same origin for rev and RRE. Our hypothesis may provide a new
      insight into the evolutionary aspect of RNA-binding transactivators.

PMID- 8307168
TI  - Acidic pH enables caeruloplasmin to catalyse the modification of low-density
      lipoprotein.
AB  - LDL oxidation within the arterial wall may contribute to the disease of
      atherosclerosis. There is some evidence that elevated plasma levels of copper are
      associated with an increased risk of coronary artery disease. We have
      investigated the conditions under which caeruloplasmin (the plasma copper carrier
      protein) can catalyse the macrophage-mediated modification of LDL. Low
      concentrations of CuSO4 (< 1 microM) could catalyse the macrophage-mediated
      modification of LDL. Native caeruloplasmin was unable to catalyse the
      modification of LDL at pH 7.4, but could do so after preincubation at acidic pH.
      After preincubation at acidic pH, concentrations of caeruloplasmin as low as 30
      micrograms/ml (about one-tenth of the human plasma level) could catalyse
      significant LDL oxidation when added to macrophages. The activation of copper in
      caeruloplasmin in atherosclerotic lesions due to a localised acidic pH may help
      to explain why LDL oxidation occurs in these areas of the body.

PMID- 8307169
TI  - The binding site of the transcriptional activator VirG from Agrobacterium
      comprises both conserved and specific nonconserved sequences.
AB  - Virulence genes of Agrobacterium tumefaciens are transcriptionally activated in
      response to phenolic compounds and certain sugars. The transcription activator
      VirG specifically binds to fragments containing the conserved vir box sequence
      present in the promoter region of all vir genes. This study shows that both the
      vir box as well as specific nonconserved sequences downstream of the vir box are
      required for VirG binding and transcriptional activation. Insertion of the
      identified VirG binding site into the lac promoter resulted in transcriptional
      activation of this heterologous promoter in response to the plant phenolic signal
      molecule acetosyringone.

PMID- 8307170
TI  - Structure of the large ribosomal subunit RNA of Phytophthora megasperma, and
      phylogeny of the oomycetes.
AB  - The 5.8S and 28S rRNA sequences of the oomycete Phytophthora megasperma were
      determined in order to study the secondary structure of these molecules and to
      assess the phylogenetic position of the oomycetes among the eukaryotes.
      Preliminary results point to an affiliation between the oomycetes,
      dinoflagellates and ciliates, a cluster which seems related to the fungi. In the
      course of this work, we developed a set of primers which allow sequencing and PCR
      amplification of eukaryotic large ribosomal subunit RNA genes of a wide range of
      phylogenetically distant organisms.

PMID- 8307171
TI  - Vitamin K-antagonistic effect of plastoquinone and ubiquinone derivatives in
      vitro.
AB  - Decyl-ubiquinone and decyl-plastoquinone were used as model compounds to test the
      potential effect of quinone derivatives on two enzymes of the vitamin K cycle in
      vitro. Substantial inhibition of gamma-glutamate carboxylase was found, whereas
      vitamin K-epoxide reductase was inhibited to a much lesser extent. The inhibitory
      effect of both decylquinones was eliminated in a time-dependent way by
      solubilized microsomes, but not by purified carboxylase. Since a wide variety of
      prenylquinones occur as micronutrients, these results are of potential relevance
      for the effects of natural quinones in the human diet.

PMID- 8307172
TI  - Furin has the proalbumin substrate specificity and serpin inhibitory properties
      of an in situ hepatic convertase.
AB  - Furin, a KEX2 protease homolog with high RNA expression in the liver is an
      excellent candidate as a hepatic proprotein convertase. Here we show that
      purified recombinant furin has the same proalbumin specificity and serpin
      inhibitory properties as the in situ hepatic convertase. There was rapid cleavage
      at the -RRD- site of normal human proalbumin but there no significant cleavage of
      natural unprocessed variants with cleavage site sequences of -RRV-, -HRD-, -RQD-,
      or -CRD-. Cleavage of the latter was not increased by S-aminoethylation. Furin
      was specifically inhibited by alpha 1-antitrypsin Pittsburgh (358 Met-->Arg),
      (K1/2 = 3 microM) but not by 50 microM normal antitrypsin M or by antithrombin,
      however, antithrombin/heparin was a good inhibitor (K1/2 = 9 microM). The pH
      optimum for proalbumin cleavage was between pH 5.5 and 6.0, indicating that furin
      is potentially fully active within secretory vesicles, the site of proalbumin
      cleavage.

PMID- 8307174
TI  - The major cold shock protein of Bacillus subtilis CspB binds with high affinity
      to the ATTGG- and CCAAT sequences in single stranded oligonucleotides.
AB  - We have characterized the nucleic acid binding properties of the major cold shock
      protein of Bacillus subtilis, CspB. CspB is a member of the cold shock domain
      (CSD) family, which is widespread among pro- and eukaryotes and shares the
      nucleic acid binding domain CSD. The CSD domain is highly conserved and binds
      with strong affinity to the Y-box motif, a cis-element that contains the
      CTGATTGGC/TC/TAA sequence. In a series of gel retardation experiments using
      oligonucleotides, which contain the Y-box motif and altered sequences, we show
      the preferential binding of CspB to single-stranded DNA that contains the ATTGG
      as well as the complementary CCAAT Y-box core sequence. In contrast CspB exhibits
      lower affinity to altered Y-box core sequences. Dependent on the length of the
      oligonucleotide and the degree of sequence deviation from the Y-box core sequence
      3- to over 10-fold overexcess of CspB was needed for complete retardation.

PMID- 8307173
TI  - The prokaryotic thermophilic TF1-ATPase is functionally compatible with the
      eukaryotic CFo-part of the chloroplast ATP-synthase.
AB  - The ATP synthase from chloroplasts, CFo.F1, was reconstituted into liposomes,
      from which most of CF1 was removed by a short treatment with guanidinium
      chloride. ATP-dependent proton uptake was restored with these CFo-liposomes even
      better by the addition of the bacterial TF1-than of the related CF1-part. This
      proton uptake was prevented by tentoxin, a specific inhibitor of the CF1-ATPase,
      in these CFo.F1-liposomes, but not in the hybrid CFo.TF1-liposomes. Venturicidin,
      a specific inhibitor of proton flow through CFo, was able to block it in both the
      hybrid CFo.TF1-liposomes and reconstituted CFo.F1-liposomes. These results
      indicate that the bacterial TF1-part binds to the eukaryotic CFo-part of four
      subunits forming a functional CFo.TF1-ATPase.

PMID- 8307175
TI  - A novel gene delivery system using EGF receptor-mediated endocytosis.
AB  - A monoclonal antibody to the human epidermal growth factor (EGF) receptor was
      conjugated with polylysine and the resulting conjugate was affinity-linked with
      DNA (gene). This novel gene delivery system utilizes receptor-mediated
      endocytosis and would be especially suitable for gene therapy for EGF receptor
      overproducing squamous cell carcinomas.

PMID- 8307176
TI  - Cloning and expression of three isoforms of the human EP3 prostanoid receptor.
AB  - Functional cDNA clones coding for three isoforms of the human prostaglandin E
      receptor EP3 subtype have been isolated from kidney and uterus cDNA libraries.
      The three isoforms, designated hEP3-I, hEP3-II and hEP3-III, have open reading
      frames corresponding to 390, 388 and 365 amino acids, respectively. They differ
      only in the length and amino acid composition of their carboxy-terminal regions,
      beginning at position 360. The human EP3 receptor has seven predicted
      transmembrane spanning domains and therefore belongs to the G-protein-coupled
      receptor family. The rank order of potency for prostaglandins and related analogs
      in competition for [3H]PGE2 specific binding to membranes prepared from
      transfected COS cells was comparable for all three isoforms, and as predicted for
      the EP3 receptor, with PGE2 = PGE1 >> PGF2 alpha = iloprost > PGD2 >> U46619. In
      addition, the EP3-selective agonist MB28767 was a potent competing ligand with an
      IC50 value of 0.3 nM, whereas the EP1-selective antagonist AH6909 gave IC50
      values of 2-7 microM and the EP2-selective agonist butaprost was inactive. In
      summary, we have cloned three isoforms of the human EP3 receptor having
      comparable ligand binding properties.

PMID- 8307177
TI  - Comparison of different ribozymes for efficient and specific cleavage of BCR/ABL
      related mRNAs.
AB  - In chronic myelogenous leukemia (CML) the reciprocal translocation of the long
      arms of chromosomes results in the formation of the unique BCR/ABL fusion gene
      which is believed to play a crucial role in the pathogenesis of CML. Different
      short synthetic ribozyme constructs were compared with regard to their efficiency
      to cleave the BCR/ABL target RNA. In the CML cell line K562 we were able to
      inhibit the p210BCR/ABL synthesis by a ribozyme which was about twofold more
      effective than the corresponding antisense molecule.

PMID- 8307178
TI  - On the tertiary structure of the Citrus ichangensis satellite DNA.
AB  - A hexamer of the repeating unit of Citrus ichangensis satellite DNA was cloned.
      Polyacrylamide gel electrophoresis demonstrated that the shape of cloned hexamer
      is other than linear. As the computing of tertiary coordinates made by Eckdahl
      and Anderson's BEN program proved, the hexamer is a solenoid consisting of two
      turns termed coiled double helix (CDH)-form. An electron microscopic analysis
      revealed small diameter circles in the hexamer under investigation. Unlike the
      hexamer control molecules are s-shaped. It is concluded that the CDH-form is a
      characteristic of the satellite DNA of Citrus ichangensis.

PMID- 8307179
TI  - Analysis of an insulin gene transcription control element. Positive and negative
      regulation appears to be mediated by different element sequences.
AB  - Pancreatic beta-cell-type-specific transcription of the insulin gene is
      controlled by cis-acting sequence elements lying within its enhancer region. An
      essential element required for expression is the insulin control element (ICE).
      The activity of this element is regulated by both positive- and negative-acting
      transcription factors. In this study, we have identified the nucleotide sequences
      within the ICE that are required for repression in noninsulin producing cells.
      Our results indicate that the cis-acting sequences involved in negative control
      are distinct from those required in activating expression in beta cells.

PMID- 8307180
TI  - Spectroscopic characterization of PS I core complexes from thermophilic
      Synechococcus sp. Identical reoxidation kinetics of A1- before and after removal
      of the iron-sulfur-clusters FA and FB.
AB  - Monomeric and trimeric PS I complexes missing the three stromal subunits E,C and
      D (termed PS I core complexes) were prepared from the thermophilic cyanobacterium
      Synechococcus sp. by incubation with urea. The subunits E,C and D are
      sequentially removed. In the monomeric PS I the subunit C is removed with a half
      life of approx. 5 min. This is about eight times faster than in the trimeric PS I
      complex. In parallel with the removal of the FA/B containing subunit C the
      reduction kinetics of P700+ changed from a half life of about 25 ms to about 750
      microseconds. The partner of P700+ in the 750 microseconds charge recombination
      was identified to be FX by the difference spectrum of this phase. There are some
      minor differences in the spectra of trimeric and monomeric PS I core complexes.
      At 77K the forward electron transfer from A1- to FX is blocked in the major
      fraction of the PS I core complexes and P700+ A1- recombines with a half life of
      about 220 microseconds. In the remaining fraction P700+FX- is formed and decays
      with a half life of approx. 10 ms at 77 K. The kinetics of the forward electron
      transfer from A1- to the iron-sulfur-clusters was measured in the native PS I and
      the corresponding core complexes. The reoxidation kinetics of A1- are identical
      in both cases (t1/2 = 180 ns). We conclude that FX is an obligatory intermediate
      in the normal forward electron transfer.

PMID- 8307181
TI  - Light-dependent in vivo phosphorylation of an inhibitory subunit of cGMP
      phosphodiesterase in frog rod photoreceptor outer segments.
AB  - In vivo phosphorylation of P gamma, an inhibitory subunit of cGMP
      phosphodiesterase of frog (Rana catesbeiana) photoreceptor rod outer segments,
      was investigated using a quick-freezing technique and a newly developed method
      for the preparation of rod outer segments. Light-dependent phosphorylation of P
      gamma was observed. Okadaic acid, a potent inhibitor of protein phosphatases 1
      and 2A, enhanced the apparent incorporation of 32P into P gamma, suggesting that
      P gamma is in equilibrium between phosphorylation and dephosphorylation. Neither
      phorbol ester, a potent activator of protein kinase C, nor changes in the
      extracellular Ca2+ concentration affected the in vivo phosphorylation of P gamma.

PMID- 8307182
TI  - Effects of morphine on prolactin receptors in the rat brain.
AB  - The effect of chronically given morphine on the binding of ovine prolactin (oPRL)
      to specific areas in the male rat brain was studied. The drug was delivered
      through subcutaneously implanted miniosmotic pumps. The results indicated that
      the density of prolactin binding sites in the hypothalamus and the choroid plexus
      was significantly decreased in the acute phase of morphine administration but
      restored to control levels when tolerance to morphine was developed. The decrease
      in prolactin binding was contrasted by elevated plasma levels of the hormone. A
      negative correlation was found between the hormone concentration in plasma and
      the density of its binding sites in the hypothalamus and choroid plexus. The
      hormone-binding sites in these two regions were further characterized with regard
      to binding constants and molecular sizes. The relevance of the present results
      with respect to the hypothalamic control of prolactin secretion is discussed.

PMID- 8307183
TI  - Differentiation of PC12 cells in response to a cAMP analogue is accompanied by
      sustained activation of mitogen-activated protein kinase. Comparison with the
      effects of insulin, growth factors and phorbol esters.
AB  - It has been proposed previously that the sustained activation of mitogen
      activated protein kinase may be necessary for the differentiation of PC12 cells.
      Differentiation of PC12 cells is induced by many extracellular agonists including
      nerve growth factor (NGF) and cyclicAMP analogues, but not epidermal growth
      factor (EGF), insulin or phorbol esters. Our results demonstrate that: (i) 8-(4
      chlorophenylthio)-cyclicAMP (CPT-cAMP) activates MAP kinase; this raises the
      possibility that the MAP kinase pathway may be activated by agents that act
      through adenylate cyclase; (ii) NGF and CPT-cAMP as well as phorbol esters
      promote sustained activation of MAP kinase. This suggests that while sustained
      MAP kinase activation may be associated with differentiation it may not be
      sufficient, and that other as yet unidentified parallel pathways may be involved.

PMID- 8307184
TI  - Enhancement of hydrogen peroxide-induced luminol-dependent chemiluminescence by
      neopterin depends on the presence of iron chelator complexes.
AB  - We have previously shown that neopterin, 6-D-erythro-trihydroxypropyl-pteridine,
      synthesized by human monocytes/macrophages upon stimulation by interferon-gamma,
      enhances toxicity of reactive oxygen at neutral or slightly alkaline pH (7.5),
      but not at acidic pH (below 6.5). In the present study, we explored in more
      detail the necessary requirements for neopterin to modulate the effects of
      hydrogen peroxide in a luminol-dependent chemiluminescence assay. We demonstrate
      that neopterin enhances hydrogen peroxide effects only in the presence of iron
      chelator complexes like iron-(III)- or iron-(II)-EDTA or iron-(III)-DTPA. Thus,
      iron chelator complexes together with neopterin may play an important role in
      macrophage-mediated effector mechanisms.

PMID- 8307185
TI  - Structural implications for the role of the N terminus in the 'superactivation'
      of collagenases. A crystallographic study.
AB  - For the collagenases PMNL-CL and FIB-CL, the presence of the N-terminal Phe79
      correlates with an increase in proteolytic activity. We have determined the X-ray
      crystal structure of the recombinant Phe79-Gly242 catalytic domain of human
      neutrophil collagenase (PMNL-CL, MMP-8) using the recently solved model of the
      Met80-Gly242 form for phasing and subsequently refined it to a final
      crystallographic R-factor of 18.0% at 2.5 A resolution. The PMNL-CL catalytic
      domain is a spherical molecule with a flat active site cleft separating a smaller
      C-terminal subdomain from a bigger N-terminal domain, that harbours two zinc
      ions, namely a 'structural' and a 'catalytic' zinc, and two calcium ions. The N
      terminal segment prior to Pro86, which is disordered in the Met80-Gly242 form,
      packs against a concave hydrophobic surface made by the C-terminal helix. The N
      terminal Phe79 ammonium group makes a salt link with the side chain carboxylate
      group of the strictly conserved Asp232. Stabilization of the catalytic site might
      be conferred via strong hydrogen bonds made by the adjacent, likewise strictly
      conserved Asp233 with the characteristic 'Met-turn', which forms the base of the
      active site residues.

PMID- 8307186
TI  - Changes in alpha 1-adrenoceptor coupling to Ca2+ channels during development in
      rat heart.
AB  - It has been reported in the literature that alpha 1-adrenoceptor activation in
      adult rat heart does not cause an increase in Ca2+ current but involves a
      decrease in I(t). This may explain in part the positive inotropic effect of alpha
      1-adrenoceptor activation. In this study, the effect of phenylephrine, an alpha
      adrenergic agonist, on L-type Ca2+ channel current was compared in young and
      neonatal rat myocytes. In the presence of propranolol, phenylephrine increased
      the Ca2+ current (reversed by prazosin) in neonatal but not in young rat myocytes
      suggesting that the coupling of the alpha 1-adrenoceptor to Ca2+ channels may
      switch during development.

PMID- 8307187
TI  - Receptor-mediated endocytosis of plasminogen activators and activator/inhibitor
      complexes.
AB  - Recent findings have elucidated the mechanism for clearance from the
      extracellular space of the two types of plasminogen activators, urokinase-type
      plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA), and
      their type-1 inhibitor (PAI-1). Activator/PAI-1 complexes and uncomplexed t-PA
      bind to the multi-ligand receptors alpha 2-macroglobulin receptor/low density
      lipoprotein receptor-related protein (alpha 2MR) and epithelial glycoprotein 330
      (gp330). These receptors mediate endocytosis and degradation of u-PA/PAI-1
      complex bound to the glycosyl phosphatidyl inositol-anchored urokinase receptor
      (u-PAR) on cell surfaces, and participate, in cooperation with other receptors,
      in hepatic clearance of activator/PAI-1 complexes and uncomplexed t-PA from blood
      plasma. The alpha 2MR- and gp330-mediated endocytosis of a ligand (u-PA/PAI-1
      complex) initially bound to another receptor (u-PAR) is a novel kind of
      interaction between membrane receptors. Binding to alpha 2MR and gp330 is a novel
      kind of molecular recognition of serine proteinases and serpins.

PMID- 8307188
TI  - Protein dynamics.
AB  - Modern NMR has revitalized the study of protein dynamics. Multidimensional
      spectra and the heteronuclear spectroscopy allow a substantial gain in
      resolution. Dynamics can be analyzed at individual sites and data on segmental
      and sequence-dependent flexibility are accumulating. This review summarizes the
      wide variety of NMR approaches for observing internal motions, including the
      folding processes, and the attempts to correlate dynamics to the biological
      activity of proteins. The implications of mobility on structure determination by
      NMR is also discussed.

PMID- 8307189
TI  - Sequence similarity of mammalian epoxide hydrolases to the bacterial haloalkane
      dehalogenase and other related proteins. Implication for the potential catalytic
      mechanism of enzymatic epoxide hydrolysis.
AB  - Direct comparison of the amino acid sequences of microsomal and soluble epoxide
      hydrolase superficially indicates that these enzymes are unrelated. Both
      proteins, however, share significant sequence similarity to a bacterial
      haloalkane dehalogenase that has earlier been shown to belong to the alpha/beta
      hydrolase fold family of enzymes. The catalytic mechanism for the dehalogenase
      has been elucidated in detail [Verschueren et al. (1993) Nature 363, 693-698] and
      proceeds via an ester intermediate where the substrate is covalently bound to the
      enzyme. From these observations we conclude (i) that microsomal and soluble
      epoxide hydrolase are distantly related enzymes that have evolved from a common
      ancestral protein together with the haloalkane dehalogenase and a variety of
      other proteins specified in the present paper, (ii) that these enzymes most
      likely belong to the alpha/beta hydrolase fold family of enzymes and (iii) that
      the enzymatic epoxide hydrolysis proceeds via a hydroxy ester intermediate, in
      contrast to the presently favoured base-catalyzed direct attack of the epoxide by
      an activated water.

PMID- 8307190
TI  - Molecular cloning and expression of a novel type V adenylyl cyclase from rabbit
      myocardium.
AB  - A cDNA of a novel form of type V adenylyl cyclase has been cloned from rabbit
      myocardium using oligonucleotide probes derived from peptides that were produced
      by enzymatic cleavage of purified heart cyclase. A corresponding mRNA (6 kb) has
      been detected in rabbit myocardial tissue by Northern blot analysis. The cDNA
      encodes a protein of 1,264 amino acids exhibiting 12 putative membrane-spanning
      regions in its hydrophilicity profile. Sequence comparison to two other
      previously published type V adenylyl cyclase reveals amino-terminal domains of
      different length and low correlative homology, whereas the rest of the sequences
      is almost identical. The nonconserved amino-terminal region of the subtype
      consists of 214 amino acids and exceeds the length of the others by 40 and 80
      residues, respectively. Its presence in membrane preparations from different
      tissues has been confirmed immunologically using an antibody directed against a
      synthetic peptide. The cloned adenylyl cyclase was functionally expressed in COS
      1 cells to attain an enzymatic activity 3.5- to 14-fold above control in the
      presence of forskolin.

PMID- 8307191
TI  - Pertussis toxin-catalyzed ADP-ribosylation of GTP-binding proteins with
      digoxigenin-conjugated NAD. Identification of the proteins in plasma membranes
      and nuclei.
AB  - ADP-ribose moiety containing digoxigenin was transferred by pertussis toxin (IAP)
      to the alpha subunit of Gi (Gi alpha) from digoxigenin-conjugated NAD (DIG-NAD)
      in a beta gamma subunit-dependent manner. ADP-ribosylation of Gi alpha with DIG
      NAD plus IAP was inhibited by native NAD. These results indicate that non
      radiolabeled DIG-NAD also serves as the substrate for IAP-catalyzed ADP
      ribosylation of G proteins. Using DIG-NAD and fluorescein isothiocyanate-labeled
      anti-digoxigenin antibody, IAP-sensitive G protein(s) was found to be exist in
      nuclei as well as plasma membranes of rat liver and HeLa cells. Thus, DIG-NAD is
      useful to identify pertussis toxin-substrate G proteins.

PMID- 8307192
TI  - The atomic structure of Carnation Mottle Virus capsid protein.
AB  - The structure of the Carnation Mottle Virus (CMtV) capsid protein has been
      determined at 3.2 A resolution by the method of molecular replacement. Three
      dimensional data were collected from a small number of crystals (sp.g. I23, a =
      382.6 A) using the synchrotron radiation with an image plate as detector. The
      coordinates of Tomato Bushy Stunt Virus (TBSV) were used as a searching model.
      Refinement of the coordinates of 7,479 non-hydrogen atoms performed by the
      program XPLOR, has led to an R-factor of 18.3%. It was found that the amino acid
      chain fold of capsid protein is very similar to that in other icosahedral
      viruses. However, there are some differences in the contact regions between
      protein subunits and also the lack of the beta-annulus around the 3-fold
      icosahedral axes. The structural and biochemical results lead us to consider an
      alternative assembly pathway.

PMID- 8307193
TI  - Enterocytic differentiation of the human Caco-2 cell line is correlated with down
      regulation of fibronectin and laminin.
AB  - Human intestinal Caco-2 cells were used to examine the expression of fibronectin
      (FN) and laminin (LN) during enterocytic differentiation. Combination of
      immunoprecipitation, Western and Northern blotting revealed that Caco-2 cells
      expressed a classical FN and a variant form of LN: besides B1 and B2 chains, LN
      contained a 350-kDa heavy chain instead of the 400-kDa A chain. Throughout Caco-2
      cell differentiation, FN and LN synthesis decreased at both mRNA and protein
      levels. These data indicate that enterocytic differentiation involves both
      transcriptional and/or post-transcriptional down-regulation of FN and LN gene
      expression.

PMID- 8307194
TI  - Calcium influx blocks the skeletal muscle acetylcholine receptor alpha-subunit
      gene in vivo.
AB  - The transcriptional activity of the acetylcholine receptor alpha-subunit gene was
      measured in denervated chick skeletal muscle in response to calcium-active drugs,
      using a ribonuclease protection version of the conventional run-off assay. The L
      channel agonist (-)Bay-K6844 and the calcium ionophore A23187 mimicked, and the
      intracellular chelator BAPTA and the calcium channel blockers D600 and nifedipine
      blocked, the effect of electrostimulation. These results suggest that influx of
      extracellular calcium is an integral component of the membrane depolarization
      receptor gene inactivation cascade.

PMID- 8307195
TI  - Effects of calcium ions on proteolytic processing of HIV-1 gp160 precursor and on
      cell fusion.
AB  - Complete activation of human immunodeficiency virus type 1 (HIV-1) requires the
      endoproteolytic cleavage by cellular protease of the envelope glycoprotein
      precursor (gp160) into the external glycoprotein gp120, and the transmembrane
      glycoprotein gp41. We report here the effect of depletion of cellular calcium
      ions on maturation of precursor gp160 and its concomitant effect on syncytium
      formation. We show that the cellular endoprotease activity responsible for gp160
      maturation and the capacity for HIV-1 to induce syncytium formation are calcium
      dependent. In addition, we show that endoproteolytic maturation is a key step in
      syncytium formation induced by HIV-1.

PMID- 8307196
TI  - Superoxide production by cytochrome b559. Mechanism of cytosol-independent
      activation.
AB  - Purified cytochrome b559 relipidated with either a mixture of phosphatidylcholine
      and phosphatidic acid or with phosphatidylcholine only exhibits high and low
      superoxide (O2-) producing ability, respectively, in the absence of cytosolic
      activators [Koshkin, V. and Pick, E. (1993) FEBS Lett. 327, 57-62]. This system
      was used as a model for the study of the mechanism of NADPH oxidase activation.
      It is shown that, depending on the composition of the phospholipid environment,
      cytochrome b599 binds FAD with high or low affinity, this being accompanied by
      changes in flavin absorbance and fluorescence. High affinity binding of FAD to
      cytochrome b559 relipidated with phosphatidylcholine combined with phosphatidic
      acid is associated with an enhanced NADPH-driven O2- producing capacity. A
      kinetic study of O2- production by cytochrome b559 reflavinated under
      stoichiometric FAD binding conditions revealed an FAD/heme ratio of 1:2. A
      further kinetic study of O2- production by high- and low-activity relipidated and
      reflavinated cytochrome b559, at varying substrate concentrations, and the
      determination of steady-state difference spectra of such preparations, reduced by
      NADPH, indicated that O2- production is activated by facilitation of electron
      transfer from NADPH to FAD rather than by an enhancement of NADPH binding.

PMID- 8307197
TI  - Cloning of eggplant hypocotyl cDNAs encoding cytochromes P450 belonging to a
      novel family (CYP77).
AB  - From eggplant hypocotyl tissues we have cloned two closely related cDNAs encoding
      cytochromes P450 (P450s) by PCR amplification using a primer designed based on
      the highly conserved sequence among the known eggplant P450s. One cDNA lacks the
      NH2-terminal short sequence that is present in the other, full-length cDNA. The
      two predicted protein sequences are 71% identical with each other and show less
      than 30% identity with any other known P450s. It is concluded that these P450s,
      which are termed CYP77A1 and -A2, belong to a hitherto unknown P450 family.

PMID- 8307198
TI  - Identification of mRNAs encoding two different soluble forms of the human
      interferon alpha-receptor.
AB  - Transcripts of the human IFN alpha-receptor (IFNAR) gene, lacking the
      transmembrane (TM) domain were found in human myeloma U266S cells, in addition to
      the transmembranal IFNAR cDNA. Two different cDNAs encoding such soluble IFNAR
      forms were identified. Form 1 has a deletion causing a frameshift toward the end
      of the extracellular (EC) domain predicting a tail of 7 amino acids. Form 2 has
      two in-frame deletions and conserves most of the intracytoplasmatic domain of
      IFNAR. The transcripts for the two soluble forms are still found in U266R cells
      which have lost the transmembranal IFNAR transcript. Human cells seem to have
      independent mechanisms to synthesize soluble IFN receptors, which may act as
      competitors outside the cells or carry IFN-mediated functions inside the cell.

PMID- 8307199
TI  - Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor
      related protein is increased in reactive and neoplastic glial cells.
AB  - alpha 2-Macroglobulin receptor/low density lipoprotein receptor-related protein
      (alpha 2M-R/LRP) is a multi-functional cell-surface receptor that has been
      implicated in diverse physiologic processes. In normal human brain, alpha 2M
      R/LRP is expressed principally by pyramidal neurons with localization to cell
      bodies and proximal processes. By contrast, alpha 2M-R/LRP is not present in
      either the cell bodies or processes of most normal macroglia (including
      astrocytes). In this investigation, we studied the expression of alpha 2M-R/LRP
      in the brain, following tissue injury or neoplastic transformation, by
      immunohistochemistry. Significantly increased alpha 2M-R/LRP immunoreactivity was
      identified in reactive astrocytes, indicating the expression of this receptor is
      regulated in vivo in response to brain injury. alpha 2M-R/LRP immunoreactivity
      was also detected in glial cell tumors; this finding is novel since malignant
      transformation is typically thought to turn off expression of this receptor.

PMID- 8307200
TI  - Ubiquitin gene expression is increased in skeletal muscle of tumour-bearing rats.
AB  - Rats bearing the fast-growing AH-130 Yoshida ascites hepatoma showed a marked
      cachectic response which has been previously reported [Tessitore et al. (1987)
      Biochem. J. 241, 153-159]. Thus tumour-bearing animals showed significant
      decreases in body and muscle weight (soleus and gastrocnemius) as compared to
      both pair-fed and ad libitum-fed animals. These decreases were related to an
      enhanced proteolytic rate in the muscles of the tumour-bearing animals as
      measured by the tyrosine released in in vitro assays. In an attempt to elucidate
      which proteolytic system is directly responsible for the decrease in muscle mass,
      we have studied both lysosomal and non-lysosomal (ATP-dependent) proteolytic
      systems in this animal model. While the enzymatic activities of the main
      cathepsin (B and B + L) systems were actually decreased in gastrocnemius muscles
      of tumour-bearing rats, thus indicating that lysosomal proteolysis was not
      involved, the ubiquitin pools (both free and conjugated) were markedly altered as
      a result of tumour burden. These were associated with an increased ubiquitin gene
      expression in muscle of tumour-bearing rats, over 500% in relation to non-tumour
      bearers, thus suggesting that the ATP-dependent proteolytic system may be
      responsible for the muscle proteolysis and wastage observed in this animal tumour
      model. The fact that we have previously shown that TNF enhances the
      ubiquitinization of muscle proteins [Garcia-Martinez et al. (1993) FEBS Lett.
      323, 211-214], together with the high circulating levels of TNF detected in rats
      bearing the Yoshida hepatoma allows us to suggest that the cytokine may be
      responsible, most probably indirectly, for the activation of the referred
      proteolytic system in tumour-bearing rats.

PMID- 8307201
TI  - Antisense retinoic acid receptor gamma-1 oligonucleotide enhances chondrogenesis
      of mouse limb mesenchymal cells in vitro.
AB  - Retinoic acid receptor (RAR) gamma gene is expressed in the precartilaginous
      cells during chondrogenesis in mouse embryos, but the role of the gene products
      is still unclear. To examine the role during chondrogenesis, we isolated
      mesenchymal cells from the limb bud of mouse embryos and exposed them to
      antisense RAR gamma-1 oligodeoxynucleotide in micromass culture. The antisense
      oligodeoxynucleotide inhibited RAR gamma-1 protein expression and enhanced
      chondrogenesis in the exposed cells. These results suggest that the complex of
      RAR gamma-1 protein and its ligand RA acts as a suppressor of the chondrogenesis
      in the limb development.

PMID- 8307202
TI  - Antisense c-myc oligonucleotide promotes chondrogenesis and enhances RA
      responsiveness of mouse limb mesenchymal cells in vitro.
AB  - To examine the role of c-myc protein during chondrogenesis, we exposed 11 day
      p.c. mouse limb mesenchymal cells to the antisense c-myc oligonucleotide in
      micromass culture. The antisense oligonucleotide inhibited the c-myc protein
      expression, and intensely promoted chondrogenesis in the exposed cells. Most of
      the cells differentiated into cartilaginous cells, whereas they differentiated
      into cartilaginous and fibrous cells under the control conditions. The antisense
      oligonucleotide increased the inhibitory efficiency of all-trans retinoic acid
      (RA) to the chondrogenesis. These results suggest that the c-myc protein suppress
      the chondrogenesis and reduces RA responsiveness in the limb mesenchymal cells.

PMID- 8307203
TI  - Interaction of protein ligands with receptor fragments. On the residues of
      curaremimetic toxins that recognize fragments 128-142 and 185-199 of the alpha
      subunit of the nicotinic acetylcholine receptor.
AB  - Using a solid-phase assay, we found that 3H-labeled alpha Cobtx from Naja naja
      siamensis, a long-chain curaremimetic toxin, and 3H-labelled toxin alpha from
      Naja nigricollis, a short-chain toxin both bind specifically but with
      substantially different affinities (Kd = 4 x 10(-7) M and 50 x 10(-6) M) to
      fragment 185-199 (T alpha 185-199) of the alpha-subunit of the acetylcholine
      receptor (AcChoR) from Torpedo marmorata. Then we show that monoderivatizations
      of residues common to both long-chain and short-chain toxins (Tyr-25, Lys-27, Trp
      29, and Lys-53) or to long-chain toxins only (Cys-30 and Cys-34) do not affect
      the binding of the toxins to T alpha 185-199, suggesting that none of these
      invariant residues in implicated in the recognition of this AcChoR region. alpha
      Cobtx and toxin alpha bind to the fragment 128-142 (T alpha 128-142) with more
      similar affinities (Kd = 3 x 10(-7) M and 1.4 x 10(-6) M) and their binding is
      dramatically affected by the single abolition of the positive charge of Lys-53,
      an invariant residue that contributes to AcChoR recognition. Therefore, the data
      indicate that Lys-53 more specifically recognizes the 128-142 region of AcChoR.
      Other monoderivatizations have no effect on toxin binding. The approach described
      in this paper may be of great help to identify toxin residues that establish
      direct contact with receptor fragments.

PMID- 8307204
TI  - Percutaneous transluminal angioplasty and surgery of the renal artery.
AB  - The management of patients with renal artery disease has changed in recent years.
      This has occurred due to the advent of PTA as an effective method of treatment
      for certain patients, an enhanced appreciation of advanced atherosclerotic renal
      artery disease as a correctable cause of renal failure, and improved results of
      surgical revascularisation in both older patients with severe aortic
      atherosclerosis and younger patients with branch renal artery disease. PTA
      currently yields excellent results and is the treatment of choice for patients
      with fibrous dysplasia of the main renal artery and non-ostial atherosclerotic
      lesions. Most reports in the literature indicate that surgical revascularisation
      provides more effective therapy for patients with ostial atherosclerotic lesions.
      Surgical revascularisation also remains the treatment of choice for the majority
      of patients with branch renal artery disease, a renal artery aneurysm, renal
      artery occlusion, and recurrent renal artery stenosis after failed PTA or
      surgery. Excellent clinical results can be achieved with both PTA and surgical
      revascularisation in properly selected patients.

PMID- 8307205
TI  - von Willebrand factor, endothelial cell damage and atherosclerosis.
AB  - von Willebrand factor (vWf) is an interesting and potentially important molecule
      whose biology in health and disease warrants attention. A growing body of
      knowledge now suggests that plasma levels of this specific product of the
      endothelial cell may have potential as a marker for the assessment of endothelial
      injury in vivo. As its functions include platelet aggregation and mediation of
      platelet adhesion to the subendothelium, it may also have a role in the
      pathogenesis of progression of atherosclerosis. In comparison to asymptomatic
      controls, increased levels of vWf are found in atherosclerotic vascular disease
      and in the presence of several of its major risk factors (smoking,
      hypercholesterolaemia, hypertension, obesity and diabetes). High plasma levels of
      vWf are also associated with the prediction of adverse clinical events such as
      myocardial infarction and poor outcome following arterial surgery, possibly by
      the promotion of thrombus formation. These and other studies indicate that
      research directed towards determining whether therapy to reduce levels of vWf
      also influences the progression of arterial disease should prove to be
      profitable.

PMID- 8307206
TI  - Axillary aneurysm: an unusual complication of haemodialysis.

PMID- 8307207
TI  - Double aortovenous fistula: a unique presentation of a ruptured abdominal aortic
      aneurysm.

PMID- 8307208
TI  - Endothelium-derived relaxing factor is absent in experimental in situ vein
      grafts.

PMID- 8307209
TI  - Cystic adventitial degeneration of the popliteal artery: lectin-histochemical
      study.
AB  - A case of cystic adventitial degeneration (CAD) of the popliteal artery is
      presented. Histologically the cyst appeared localised in the adventitia, outside
      the elastic lamina. A lectin-histochemical study evaluated the following
      peroxidase conjugated lectins: Peanut agglutinin, Concanavalin A, Ulex Europaeus
      (UEA I) and Wheat Germ Agglutinin. The lack of UEA I reactivity excluded an
      arterial origin of the cyst. Moreover, the lectin binding pattern of CAD appeared
      to be similar to the reactivity pattern of normal synovia.

PMID- 8307210
TI  - Preoperative assessment of the pedal arch using pulse generated runoff and
      subsequent femorodistal outcome.
AB  - Calf vessel continuity with an intact pedal arch is an important factor in
      femorodistal (FD) bypass for critical ischaemia. Pulse generated runoff (PGR) was
      used in combination with the pedal arch patency test of Roedersheimer to
      determine preoperatively calf vessel and pedal arch patency. Three pedal arch
      groups were identified; complete (two calf vessels in continuity), incomplete
      (one vessel) and occluded (no vessels). One hundred non-reversed FD grafts were
      performed for critical ischaemia (63 men and 37 women), median age 72 (range 43
      89 years). Sixteen grafts were to the above knee popliteal artery, 36 to the
      distal popliteal, three to the tibioperoneal trunk and 45 to a single calf
      vessel. There were 25 complete, 64 incomplete and 11 occluded pedal arches. The
      overall primary patency rate was 73%, nine grafts were successfully revised
      giving a secondary patency rate of 83.5%. The secondary graft patency rates for
      the above knee popliteal, below knee popliteal, tibioperoneal and single calf
      vessel grafts were 100, 92, 66 and 66% respectively. The 1 year graft patency
      rates for grafts to a complete, incomplete and occluded pedal arch were 88, 75
      and 9% respectively (Lee-Desu p < 0.01). Similar results were obtained for limb
      salvage; 100, 84 and 24% respectively (p < 0.01). These results confirm the value
      of PGR in the preoperative assessment of patients with critical ischaemia. In
      reconstructions to the popliteal artery, PGR derived pedal arch status does not
      appear to influence the outcome. By contrast PGR derived pedal arch status in an
      excellent predictor of success following reconstructions to a single calf
      vessel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307211
TI  - Halving the number of leg amputations: the influence of infrapopliteal bypass.
AB  - A retrospective review of amputations in patients with vascular disease during 10
      years in Bispebjerg Hospital was undertaken. There were 1383 amputations leading
      to 1167 final level amputations. In previously independent patients there were
      482 below knee amputations (BKA), 476 above knee amputations (AKA) and 43 had
      disarticulations in the ankle, knee or hip. During the period studied the number
      of final level amputations in independent patients were halved from 122 in 1981
      to 58 in 1990. A similar reduction was also found in the total number of
      amputations: from 171 to 90, and in the number of reamputations: from 35 to 21.
      However, amputations in patients from long stay institutions remained at a
      constant level by on average 17 per year. The decrease in amputation rate took
      place synchronously with an increasing use of bypass to crural and pedal arteries
      as well as an overall increase in vascular reconstructions and angioplasties of
      more than 100%. However, the BKA/AKA ratio decreased from 1.12 to 0.67 (p <
      0.005).

PMID- 8307212
TI  - Vascular surgery reduces the frequency of lower limb major amputations.
AB  - In June 1988 a Department of Vascular Surgery was established in the county of
      Viborg, Denmark. In this retrospective study of the periods 1986-87 and 1989-90,
      we have observed a significant rise in the number of patients evaluated by a
      vascular surgeon before amputation, from 19 to 49%. At the same time the number
      of major lower limb amputations significantly decreased. This reduction was most
      marked in 1990 probably due to a rise of 43% in the number of distal
      reconstructions. The distribution between below knee, through knee and mid-thigh
      amputation was unaffected by the increased vascular surgical activity. The
      frequency of major amputations in the county in 1986-87 of 40.9 per 100,000 per
      year declined by 25% to 30.9 per 100,000 per year in 1989-90. We conclude that
      vascular surgery reduces the number of major lower limb amputations and
      consequently all patients threatened with amputation must be evaluated if
      vascular reconstruction is possible.

PMID- 8307213
TI  - Spontaneous aorto-caval fistulas from ruptured abdominal aortic aneurysms.
AB  - Thirty-six cases of abdominal aortic aneurysms rupturing into the vena cava and
      two iliac aneurysms rupturing into iliac veins are reported. This group
      represents 10% of the total number of observed ruptured abdominal aortic
      aneurysms (388). Such a condition is therefore quite rare but should be
      considered positively because the reported mortality rate is less than with
      ruptured aneurysms in general. Nevertheless, a spontaneous aorto-caval fistula is
      responsible for a critical haemodynamic deterioration and sudden worsening of the
      general condition of the patient and therefore prompt surgical repair is
      mandatory. The overall mortality rate in our series was 21% (8 cases).

PMID- 8307214
TI  - Inflammation of the abdominal aortic aneurysm wall.
AB  - Inflammation and fibrosis do not only appear in an "inflammatory" aneurysm, but
      also in "ordinary" abdominal aortic aneurysms. In this study inflammatory changes
      in 130 abdominal aortic aneurysms were studied and related to patients' clinical
      records. According to histopathological criteria five different degrees of
      inflammation (Histological Inflammation Scale of Aneurysms) were found and
      patients were classified according to these criteria: grade A or mixed
      acute/chronic inflammation (4.5%); grade 0 or no inflammation (16.2%); grade 1 or
      mild chronic (57.7%); grade 2 or moderate chronic (16.2%); and grade 3 or severe
      chronic inflammation (5.4%) corresponding to an "inflammatory" aneurysm. Patients
      with grade 3 or an "inflammatory" aneurysm were younger (p = 0.013), were all
      symptomatic (p = 0.02), showed no associated iliac or femoral aneurysms (p =
      0.03), were only recognised peroperatively and had elevated erythrocyte
      sedimentation rates (p = 0.0002). No other differences could be demonstrated
      between sex, risk factors, cardiovascular diseases, previous abdominal
      operations, bacterial culture, aneurysm diameter, white blood count, cholesterol
      level in-hospital mortality when compared to the degree of inflammation.

PMID- 8307216
TI  - The comparison of type of incision for transperitoneal abdominal aortic surgery
      based on postoperative respiratory complications and morbidity.
AB  - Equal access to the abdominal aorta can be attained through midline and
      transverse abdominal incisions. The surgical literature suggests that transverse
      incisions cause less postoperative pain and morbidity. Fifty patients (10 females
      and 40 males, mean age 67 years) undergoing abdominal aortic surgery were
      randomised to a midline (n = 25) or transverse (n = 25) incision. All patients
      were evaluated preoperatively and postoperatively for seven days. Changes in
      pulmonary function (FVC and FEV1), time to open and close the incision, analgesia
      used (morphine mg/kg/h), clinical or X-ray evidence of chest infection, and the
      duration of ICU stay were recorded. In the transverse group there was a reduction
      in the incidence of chest complications (20% vs. 28%, p = ns) and these incisions
      took longer to open (13.9 +/- 4.6 vs. 9.9 +/- 5.1, p < 0.05), but overall there
      was no significant difference between any other parameter in the two groups. Our
      results show no statistically significant difference in morbidity or analgesia
      consumption following transverse or midline abdominal incisions and we conclude
      that the type of incision used can be left to the surgeon's preference.

PMID- 8307215
TI  - Long-term results of arterial reconstruction of the upper extremity.
AB  - Arterial reconstructive surgery for upper limb ischaemia of non-traumatic non
      embolic origin is uncommon in comparison to that of the lower extremities and
      long-term follow-ups are rare. Forty-eight patients (27 females, 21 males) with a
      median age of 58 years (range 22-88) were retrospectively analysed for risk
      factors, survival and patency rates. Seventy-three per cent were smokers, 42% had
      hypertension and 33% had had previous vascular interventions. Diabetes was only
      seen in 4% of the cases. Effort fatigue was the dominant cause for surgery
      followed by micro-embolism and rest pain or gangrene. The left side was more
      frequently affected with 30 procedures compared to 18 on the right. Bypass with
      either Dacron, ePTFE or autologous vein was the most frequent procedure in 56% of
      the cases followed by thrombendarterectomy (23%) and subclavio-carotid
      transposition (11%). Arm-arm index rose from 0.63 (SD 0.28) preoperatively to
      1.02 (SD 0.12) after 1 month and at the end of follow-up (median 75 months) it
      was 0.96 (SD 0.15). Cumulative survival rates were at 1 month 98%, 1 year 91%, 5
      years 81% and at 10 years 73%. Cumulative primary patency rates at the same
      intervals were 96, 96, 88 and 80%, respectively. Thus the survival rate and
      patency rate are favourable in comparison with arterial surgical procedures of
      the lower extremity.

PMID- 8307217
TI  - The clinical course of patients following extensive deep venous thrombosis.
AB  - Following deep venous thrombosis (DVT), patients may develop leg swelling, skin
      changes and ulceration. Early studies have suggested that patients suffer
      progressive deterioration and poor eventual outcome. The objective of this study
      was to determine whether extensive DVT still carries a poor prognosis. In this
      study 83 patients with 86 affected limbs were followed with annual review for 12
      135 months, median 47 months. Thirty-seven patients were referred at time of DVT
      and 46 patients referred with established symptoms following DVT. In the latter
      group, time from DVT to referral ranged from mean 2-45 years (median 7 years).
      All patients had phlebographically proven deep venous thrombosis. The main
      outcome measures were subjective improvement in symptoms, healing of leg ulcer or
      development of a new leg ulcer. Deterioration or improvement in signs of post
      thrombotic syndrome were documented by one observer (CVR). Patients were
      routinely provided with graduated compression stockings. They were given advice,
      as appropriate, on weight reduction and care of the limb. Improvement of symptoms
      was reported in 25 (29%) limbs, 49 (57%) had no change and 12 (14%) deteriorated.
      Three patients (3%) developed a new leg ulcer. The great majority of patients
      following extensive deep venous thrombosis, when provided with graduated
      compression stockings and regularly supervised, either remained stable or
      improved when followed long-term. The development of a new leg ulcer was
      uncommon. The post-thrombotic syndrome does not carry the poor prognosis reported
      in earlier studies.

PMID- 8307218
TI  - The effect of low molecular weight heparin on intimal hyperplasia in vein grafts.
AB  - Intimal hyperplasia due to smooth muscle cell proliferation is a well recognised
      cause of vascular graft failure. In experimental studies heparin and its low
      molecular weight derivatives can inhibit this proliferative response. This study
      examines the effect of subcutaneous low molecular weight heparin (LMWH) therapy
      on intimal hyperplasia in a model of arterial vein grafting. Twenty-four New
      Zealand White rabbits underwent interposition vein grafting of the carotid
      artery. Animals were randomly assigned to a control or treated group. Treated
      animals received 60 anti Xa units/kg of subcutaneous LMWH daily for 1 month.
      Animals were then sacrificed, graft patency assessed and the vessels then
      harvested for analysis of intimal hyperplasia. Intimal hyperplasia in carotid
      arteries and vein grafts was measured using a computerised image analysis system
      and was expressed as an intimal:medial area ratio. A statistically significant
      reduction in the degree of intimal hyperplasia seen in the arterial component of
      the distal anastomoses of carotid vein grafts was achieved using subcutaneous
      LMWH [Control 0.44 (0.37-0.55): LMWH 0.27 (0-0.37) p < 0.05]. There was no
      difference in the degree of intimal hyperplasia seen in the vein grafts
      themselves. [Control 0.21 (0-0.54): LMWH 0.23 (0-0.72)]. This study suggests that
      subcutaneous LMWH can inhibit the development of intimal hyperplasia in arteries
      undergoing vascular grafting but does not influence intimal hyperplasia within
      vein grafts. This has important implications for the further evaluation of
      antithrombotic agents following vascular surgery.

PMID- 8307219
TI  - Comparison of laser Doppler perfusion imaging, laser Doppler flowmetry, and
      thermographic imaging for assessment of blood flow in human skin.
AB  - In this study we compared three non-invasive methods of measuring skin perfusion,
      thermographic imaging (TI), laser Doppler flowmetry (LDF) and the new technique
      of laser Doppler imaging (LDI). Seven normal volunteers were studied in a
      temperature-controlled room with an ambient temperature of 22 +/- 1 degree C.
      Images of the left hand were recorded using LDI followed by TI. LDF was then used
      on two standard locations on the fingers and back of the hand. The measurements
      were then repeated for a hot (37 degrees C) and then a cold (10 degrees C)
      challenge. A significant linear correlation (r = 0.960, p < 0.01, with 95%
      confidence limit of 0.35-0.77, n = 38) was found between LDF and LDI. However,
      LDF and LDI did not correlate well with TI (r = 0.577, p < 0.01, with 95%
      confidence limit of 0.32-0.76, n = 38). The LDI method was found to be highly
      reproducible (mean +/- 1 SD; 625 +/- 30, with coefficient of variation 5%). The
      blood flow and temperature distribution of skin of the hand was then recorded
      using TI and LDI in 10 patients (mean age +/- SD, 41.7 +/- 9.9) with scleroderma
      and eight normal volunteers (mean age +/- SD, 30.6 +/- 6.5). The overall mean
      blood flow and temperature in the hands of patients with scleroderma (mean +/- SD
      444 +/- 265 flux, 29.3 +/- 3.3 degrees C) was significantly (p < 0.0001) lower
      compared with the normal volunteers (mean +/- SD, 912 +/- 390 flux, 34.0 +/- 3.2
      degrees).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307220
TI  - Segmental mediolytic arteritis--electronmicroscopic and immunohistochemical
      study.
AB  - We examined specimens of human gastroepiploic artery aneurysm from a patient
      having several visceral aneurysms using electronmicroscopic and
      immunohistochemical techniques. The histopathological and ultrastructural
      findings confirmed the diagnosis of segmental mediolytic arteritis. Arterial
      smooth muscle cells from the gastroepiploic artery contained cytoplasmic
      vacuoles, media was thin and the internal elastic membrane showed distortion. X
      ray microanalysis revealed calcium deposits in the medial extracellular space.
      Antigenic determinants of human immunoglobulins, fibrinogen, complement C3a and
      factor VIII were demonstrated in the injured artery wall, suggesting that
      immunocomplexes deposited in the artery wall may be associated with local injury.
      These findings support the role of autoimmune disorders in the pathogenesis of
      segmental mediolytic arteritis.

PMID- 8307221
TI  - Early reoperation rates after arterial surgery.
AB  - Between 1 January 1985 and 31 December 1991, 2426 patients underwent arterial
      surgery. Three hundred and seventy one reoperations were performed on 258
      patients within 30 days of the initial procedure. One hundred and ninety three
      (52%) of the operations were attempted revascularisations, 95 (26%) were
      amputations and 58 (16%) were to control bleeding. One hundred and sixty nine
      (66%) of first operations were successful, but 76 patients required a further 113
      reoperations. The mortality of reoperation was 16%, while the mortality of
      patients not requiring reoperation was 9% (p < 0.01). The mean hospital stay in
      days was higher in patients requiring reoperation (p < 0.05). Where appropriate,
      patients should be informed of the significant incidence of reoperation and
      reoperative mortality after vascular surgery. The increased hospital stay in
      reoperated patients has financial implications.

PMID- 8307222
TI  - Platelet inhibition with ASA/dipyridamole after percutaneous balloon angioplasty
      in patients with symptomatic lower limb arterial disease. A prospective double
      blind trial. Study group on pharmacological treatment after PTA.
AB  - A randomised double-blind multicentre trial has been performed comparing the
      influence of 3 months prophylaxis with acetylsalicylic acid/dipyridamole (50
      mg/400 mg daily) or placebo on the outcome following percutaneous transluminal
      angioplasty for lower limb ischaemia. Two hundred and twenty-three patients were
      included and followed. There were no differences between the groups regarding
      results 1, 3, 6 and 12 months following the dilatation treatment. It can be
      concluded that acetylsalicylic acid at the dose of 50 mg daily combined with
      dipyridamole does not seem to have a prophylactic effect after transluminal
      angioplasty during a follow-up period of 1 year.

PMID- 8307223
TI  - Infrarenal aortic diameter in the healthy person.
AB  - In order to determine the relevance of abdominal aortic dilatation, knowledge of
      the normal aortic diameter and its relation to age, sex and body size (height,
      weight, body surface area) is essential. The diameter of the infrarenal aorta was
      measured in 146 healthy males and females 4-74 years old with ultrasonography and
      the influence of the aforesaid factors on aortic diameter was analysed by means
      of a multiple stepwise regression model. The infrarenal aorta was found to
      increase steadily in diameter throughout life. From about 25 years the diameter
      was larger in males than in females (p < 0.01) though this difference vanished if
      corrected for differences in body surface area. Significant correlations were
      found between aortic diameter and weight (r = 0.84, p < 0.001), height (r = 0.77,
      p < 0.001) and body surface area (r = 0.83, p < 0.001). Age followed by body
      surface area were the factors most influencing aortic diameter in both males (r =
      0.92, p < 0.001) and females (r = 0.94, p < 0.001). Nomograms predicting aortic
      diameters in relation to age, sex, and body surface area are presented.

PMID- 8307224
TI  - Spontaneous intraabdominal haemorrhage caused by segmental mediolytic arteritis
      in a patient with systemic lupus erythematosus--an underestimated entity of
      autoimmune origin?
AB  - We describe the sixth known case of segmental mediolytic arteritis and the third
      in a survivor. A 70-year-old woman had intraabdominal bleeding due to a ruptured
      aneurysm of the omental artery. Interestingly, this patient also had a systemic
      lupus erythematosus. This report gives further support to the role of immune
      abnormalities underlying segmental mediolytic arteritis.

PMID- 8307225
TI  - [New aspects of prosthetic treatment in adolescents].
AB  - The authors emphasise the similarities in the prosthodontic treatment of the 14
      18 age group and adult patients. This is a new concept compared to the available
      reports in the scientific literature. According to their opinion permanent
      prosthodontic treatment should be provided from the age of fourteen.

PMID- 8307226
TI  - [Clinical experience with the use of ceramic orthodontic brackets].
AB  - The advantage and disadvantage of applying ceramic orthodontic brackets were
      compared on base of practical experiences. The application of ceramic brackets is
      recommended in the clinical practice, considering that also enamel injuries may
      develop by debonding.

PMID- 8307227
TI  - [Cleansing effect of two micromotor-driven endodontic handpieces.II. Effect of
      various rinsing solutions on the cleansing effect of the handpieces].
AB  - The cleansing effectivity of citric acid solution was significantly better than
      that of Neomagnol both with respect to the removal of the Smear Layer (SL) and to
      the number of visible dentinal tubular orifices, however a complete elimination
      of the SL could not be obtained. Neomagnol seemed to be more effective in the
      removal of superficial debris and tissue-remnants.

PMID- 8307228
TI  - [Postmortem diagnosis of primary malignant tumors in a 10-year patient material].
AB  - Dissectional data were analysed of deceased patients due of malignant tumors of
      the neck-head area, in the authors institute in the last ten years. Besides the
      fatal primary tumor in 6.1% of the cases there were clinically not, just post
      mortem diagnosed multiple tumors. The authors advise more thorough examination
      and over five years control of the patients.

PMID- 8307229
TI  - Principles of radiographic selection and interpretation.
AB  - When performing a radiologic examination, it is important for the clinician to
      follow a diagnostic sequence. Specific viewing principles are necessary to create
      the proper physical environment to obtain the most information from the
      radiographs. The selection of radiologic examination must be based on the ALARA
      (As Low As Reasonably Achievable) principle, and the clinician should use a
      method approach to radiologic interpretation.

PMID- 8307230
TI  - Periapical and localized radiopacities.
AB  - Anatomic conditions and pathologic entities that commonly present as periapical
      and solitary radiopacities are categorized according to radiographic appearance.
      Clinical criteria for establishing a differential diagnosis are presented, and
      the rationale behind treatment objectives is discussed.

PMID- 8307231
TI  - Caries, periodontal disease, and periapical changes.
AB  - Conventional radiography is the standard for diagnosis of dental disease,
      although it lacks the sensitivity to demonstrate the earliest changes of
      diagnostic significance. Imaging techniques such as direct digital radiography
      and subtraction help to better demonstrate subtle changes in diagnostic
      information.

PMID- 8307232
TI  - Generalized radiopacities.
AB  - Lesions are grouped together based on their radiographic appearances. Although
      similar in radiographic appearance, lesions often are differentiated by the age
      of the patient when first detected, sex of the patient, and site predilection. In
      some cases, lesions can be differentiated further by their prevalence rates or
      unique radiographic signs.

PMID- 8307233
TI  - Disorders of the maxillary sinus.
AB  - The maxillary sinuses often are visualized on oral and maxillofacial radiographs,
      and the dentist should be able to interpret any signs of disease in the area. In
      addition, disorders of the sinuses may result in symptoms that the patient
      interprets to be of dental origin. Conversely, dental diseases may influence the
      radiographic appearance of the sinuses. This article reviews the radiographic
      signs of common sinus disorders to help the clinician accurately assess the
      patient.

PMID- 8307234
TI  - Disorders of the temporomandibular joint.
AB  - Diagnostic imaging, however impressive and informative, is only one aspect of the
      diagnostic evaluation required to render an accurate assessment of
      temporomandibular disorders. A thorough patient history, detailed clinical
      examination, and correlation of radiographic information are essential to
      formulate the diagnosis, prognosis, and treatment plan.

PMID- 8307235
TI  - Radiolucencies with distinct borders.
AB  - The differential diagnosis of circumscribed radiolucencies or those with distinct
      borders requires careful evaluation of lesion-specific characteristics. This
      evaluation is necessary because of the variable prognosis and possible
      aggressiveness of lesions that may fall into this category, which also contains
      many benign conditions. This section reviews the clinical features, radiographic
      appearance, histopathologic findings, and treatment recommendations for a
      selected group of lesions.

PMID- 8307236
TI  - Pericoronal radiolucencies with and without radiopacities.
AB  - Pericoronal radiolucencies are common entities of the jaws that account for about
      15% to 20% of all biopsy specimens. They are usually slow-growing, benign
      entities that involve odontogenic epithelium and the crown of a nonerupting
      tooth. Many lesions develop early in life and are detected during routine
      radiographic examination. Others are found in later years when a patient presents
      with a slow-growing swelling. The dentist is often the first provider to
      encounter these conditions. Thus, he or she must be familiar with their
      appearance and understand the proper management required.

PMID- 8307237
TI  - Multilocular radiolucencies.
AB  - This article discusses lesions that commonly present as multilocular
      radiolucencies and, therefore, should be considered when the clinician is forming
      a differential diagnosis. These lesions include odontogenic keratocyst,
      ameloblastoma, central giant cell granuloma, cherubism, odontogenic myxoma,
      aneurysmal bone cyst, and central hemangioma and other vascular lesions. There is
      much variation in the clinical nature of multilocular lesions and, thus,
      variation in management. The clinician always must consider the possibility of a
      vascular lesion whenever evaluating a multilocular radiolucency.

PMID- 8307238
TI  - Radiolucencies with indistinct or ragged borders.
AB  - The diagnostic challenge will always be present when encountering an ill-defined
      radiolucency. Is it an artifact, normal anatomy, or one of these inflammatory,
      proliferative, or neoplastic disorders? If it cannot be explained as an artifact
      or anatomic variant, then consideration certainly should be given for a short
      term follow-up radiograph or immediate biopsy. Understanding the clinical,
      radiographic, and histopathologic features, as well as the treatment protocols
      for these various disorders should help the dentist make the proper diagnostic
      decisions and provide the appropriate patient management.

PMID- 8307239
TI  - Overview of pancreatic duct physiology and pathophysiology.
AB  - The epithelium of the excretory duct system of the exocrine pancreas secretes
      bicarbonate ions and mucins. Epithelial cells of the duct system also constitute
      primary sites of dysfunction in cystic fibrosis, pancreatitis and pancreatic
      cancer. The present work provides an overview of the current state of
      understanding of the physiology and pathophysiology of the pancreatic duct system
      and suggests approaches that will provide continued progress in exploration of
      the basic physiological processes operating in this tissue.

PMID- 8307240
TI  - The hypersensitive gut: adequate approach or further confusion?

PMID- 8307241
TI  - Video analysis: a method of assessing changes in preverbal and early linguistic
      communication after cochlear implantation.
AB  - As the age of cochlear implantation in children decreases, there is an increasing
      need for methods to monitor the preverbal and early linguistic development of
      children fitted with these devices. One method that has been used successfully to
      monitor children wearing acoustic amplifying hearing aids entails the video
      recording over time of child-adult interactions in a conversational setting, and
      the subsequent methodical analysis of various aspects of the interaction. These
      aspects include eye contact, turn taking, autonomy, and auditory processing. The
      same method has been applied to children wearing the Nucleus 22-electrode
      cochlear implant system. An overview is given of the video analysis results for a
      group of 10 children studied from a period before implantation up to one year
      postimplantation. The results illustrate group changes in the various measures
      due to the provision of auditory information by the cochlear implant, plus the
      scatter of individual data. It is concluded that early indications of progress
      over time generally predict the level of functioning achieved at 12 months
      postimplantation. The method provides essential objective information, which
      enables discrete changes in behavior to be monitored realistically. Two case
      studies are presented to illustrate the application of the video analysis method
      to obtain information for clinical management of children with cochlear implants.

PMID- 8307242
TI  - Self-perceived and audiometric evaluations of hearing aid benefit in the elderly.
AB  - This study was designed to monitor benefit received from the use of amplification
      by 58 elderly new hearing users. The longitudinal study assessed changes in self
      perceived handicap and audiometric measures by analyzing data at prefitting and
      at 3-wk, 3-mo, 6-mo, and 1-yr postfitting intervals. Measurement tools included
      the Hearing Handicap Inventory for the Elderly (HHIE), functional gain (500
      through 4000 Hz), and speech recognition measures in quiet and in noise. Results
      indicated a significant decrease in perceived handicap after 3 wk of hearing aid
      use. After 3 mo, perceived handicap increased significantly before leveling off
      at 6 mo and 1 yr. Audiometric measures remained constant throughout the period
      under investigation. Benefit as defined using functional gain data was unrelated
      to benefit as defined using self-report data.

PMID- 8307243
TI  - Scoring Spanish word-recognition measures.
AB  - Spanish word recognition scores were determined from 10 native Spanish-speaking
      listeners' written and oral responses to four Auditec lists (A, B, C, and D) of
      two-syllable Spanish words. An analysis of variance revealed that the word
      recognition scores derived from the oral responses were the same when scored by
      15 native English-speaking judges with a knowledge of Spanish and when scored by
      15 native English-speaking judges without a knowledge of Spanish (p > 0.01). To
      evaluate the accuracy with which these two groups of judges scored the oral
      responses, the absolute values of the numeric differences between the word
      recognition scores derived from the oral and written responses were determined.
      An analysis of variance of these absolute difference scores revealed a
      significant main effect of judges' knowledge of Spanish (p < .01). Although the
      difference between the groups of judges was statistically significant, this
      difference is of little clinical significance. The word recognition scores for
      written and oral responses differed on average by two percentage points when oral
      responses were scored by judges with a knowledge of Spanish and by three
      percentage points when oral responses were scored by the group without a
      knowledge of Spanish. These data indicate that English-speaking audiologists are
      competent to judge the accuracy of Spanish-speaking listeners' oral responses to
      Spanish word recognition measures.

PMID- 8307244
TI  - The effect of middle ear pressure on transient evoked otoacoustic emissions.
AB  - To determine the effect of middle ear pressure on transient evoked otoacoustic
      emissions (TEOAEs), emissions were recorded in ears with tympanometric peak
      pressures < or = -100 daPa and audiometric thresholds < or = 30 dB HL at 500
      through 2000 Hz. TEOAEs were alternately recorded at ambient pressure and at the
      tympanometric peak pressure. As demonstrated for the 14 ears tested, equalization
      of the middle ear pressure increased TEOAE amplitude. Reproducibility was
      similarly improved in 12 of 14 ears. Unequalized middle ear pressure attenuated
      low frequency emissions more than high frequency emissions. These amplitude and
      spectrum differences were consistent with previously reported observations of the
      effects of ear canal pressure on otoacoustic emissions. Results suggest that
      unequalized middle ear pressure may increase the occurrence of false positive
      failures, if otoacoustic emission testing is used for hearing screenings without
      consideration of middle ear pressure.

PMID- 8307245
TI  - Multifrequency tympanometry in normal adults.
AB  - Multifrequency tympanograms were recorded from 56 ears of 28 normal-hearing adult
      subjects to obtain normative data and to determine abnormal criteria for
      tympanometric measures. Static admittance, tympanometric width, and tympanometric
      peak pressure at 226 Hz were analyzed along with eight different estimates of the
      resonant frequency of the middle ear. Based on test-retest reliability and normal
      distribution characteristics, preferred methods for clinical estimation of
      resonant frequency were determined. The sweep pressure mode (ear canal pressure
      is swept while probe frequency is held constant) is preferred for detection of
      abnormally high resonant frequencies. The sweep frequency mode (probe frequency
      is swept while ear canal air pressure is held constant) is preferred for
      identification of abnormally low resonant frequencies. Compensation for ear canal
      volume at +200 daPa was preferred over other compensation methods for estimation
      of middle ear resonant frequency.

PMID- 8307246
TI  - Ambient noise levels in audiometric test rooms used for clinical audiometry.
AB  - Recently, the American National Standards Institute (ANSI) has specified (ANSI
      S3.1-1991) maximum permissible ambient noise levels (MPANLs) allowed in an
      audiometric test room that would produce negligible masking of pure tones
      presented down to O-dB HL for two test conditions (ears covered, ears not
      covered) and three test frequency ranges (125-8000 Hz, 250-8000 Hz, 500-8000 Hz).
      In the present study, octave band ambient noise sound pressure levels were
      measured in 136 audiometric test rooms used for clinical audiometry and compared
      with the ANSI octave band MPANLs for each test condition and frequency range. For
      the ears covered condition, about 50% of the rooms were in compliance (passed)
      with the MPANLs for the 125-8000 Hz and 250-8000 Hz range and 82% for the 500
      8000 Hz range. For the ears not covered condition, only about 14% of the rooms
      passed for the 125-8000 Hz and 250-8000 Hz range and 37% passed for the 500-8000
      Hz range. The primary cause of the low pass rate for each test condition and
      frequency range was attributed to low frequency (125-500 Hz) ambient noise
      presumably from the ventilation system.

PMID- 8307247
TI  - Reduced variance in the latency and amplitude of the fifth wave of auditory brain
      stem response after normalization for head size.
AB  - The value of the Auditory Brain Stem Response (ABR) in the assessment and
      detection of neurological disorders could be considerably enhanced if the
      normative standards of ABR characteristic parameters take into account all other
      systematic sources of variance. The present study attempts to take into account
      the influence of head size on latency and amplitude of the ABR components. We
      examined amplitude and latency as a function of head size in 40 normal male
      subjects (age 20-40 years). Significant negative correlation was found between
      amplitude and head radius. The experimental data were fitted using a theoretical
      curve of the potential on the surface of a three-concentric sphere model
      representing the human head. The fitted curve of amplitude versus radius can be
      applied to normative data in order to substantially reduce dispersion and
      consequently increase the diagnostic value of this parameter. Moreover, a
      substantial effect of radius on wave V latency was detected. Normalization of the
      latencies with reference to the head radius, assuming that the latter is
      proportional to the length of brain stem, resulted in a significant reduction in
      the standard deviation of these data as compared to the original.

PMID- 8307248
TI  - Metabolic origin of insulin resistance in obesity with and without type 2 (non
      insulin-dependent) diabetes mellitus.
AB  - A metabolic hypothesis is presented for insulin resistance in obesity, in the
      presence or absence of Type 2 (non-insulin-dependent) diabetes mellitus. It is
      based on physiological mechanisms including a series of negative feed-back
      mechanisms, with the inhibition of the function of the glycogen cycle in skeletal
      muscle as a consequence of decreased glucose utilization resulting from increased
      lipid oxidation in the obese. It considers the inhibition of glycogen synthase
      activity together with inhibition of glucose storage and impaired glucose
      tolerance. The prolonged duration of increased lipid oxidation, considered as the
      initial cause, may lead to Type 2 diabetes. This hypothesis is compatible with
      others based on the inhibition of insulin receptor kinase and of glucose
      transporter activities.

PMID- 8307249
TI  - Angiotensin II receptor blockade improves nerve function, modulates nerve blood
      flow and stimulates endoneurial angiogenesis in streptozotocin-diabetic rats and
      nerve function.
AB  - We examined the effect of the angiotensin II receptor blocker, ZD 8731, on nerve
      function, capillary density, and blood flow in streptozotocin-diabetic rats.
      Deficits in sciatic motor and saphenous sensory nerve conduction velocity of 21%
      and 15%, respectively, were observed after 1 month of diabetes mellitus (p <
      0.001). These were completely ameliorated by a further month of ZD 8731 treatment
      (p < 0.001). Treatment of non-diabetic rats for 1 month with ZD 8731 had no
      effect on motor or sensory conduction velocity. Sciatic nerve capillary density
      was not significantly affected by 1- or 2-month untreated diabetes, however,
      there was a 15% increase in density with ZD 8731 treatment (p < 0.001). Treatment
      of non-diabetic rats for 1 month had no effect on capillary density. Diabetes
      prolonged the time taken for 80% conduction failure by 19% (p < 0.05) and 49% (p
      < 0.001) for 1 and 2 months of diabetes, respectively, when sciatic nerve was
      exposed to hypoxia in vitro. ZD 8731 treatment during the second month of
      diabetes limited the prolongation to 22%, not significantly different from 1
      month of untreated diabetes but less than for the 2-month diabetic group (p <
      0.001). Concentrations of sciatic nerve polyol pathway metabolites were elevated
      six-fold and myo-inositol was reduced 40% by diabetes; ZD 8731 treatment was
      without effect. Acute experiments examined the effect of ZD 8731 on sciatic nerve
      blood flow using laser-Doppler flowmetry. In non-diabetic rats, blood flow
      changes followed the dose-dependent reductions in systemic arterial pressure and
      there were no significant variations in sciatic vascular resistance.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8307250
TI  - Beta-cell hypersensitivity for glucose precedes loss of glucose-induced insulin
      secretion in 90% pancreatectomized rats.
AB  - Glucose-induced insulin secretion is impaired in the presence of chronic
      hyperglycaemia. Insulin secretion was studied in a diabetic rat model prior to
      the beta cells becoming non-responsive to glucose in order to map out the
      sequence of changes that accompany chronic hyperglycaemia. In vitro pancreas
      perfusions were carried out 1 and 2 weeks after a 90% pancreatectomy; controls
      underwent a sham pancreatectomy. One week post 90% pancreatectomy: (i) non
      fasting plasma glucose values were 2-3 mmol/l above normal, (ii) the in vitro
      insulin response to 16.7 mmol/l glucose was 20 +/- 4% of shams, a response that
      was appropriate for the surgical reduction in beta-cell mass, (iii) the beta-cell
      sensitivity for glucose was increased as reflected by left-shifted dose-response
      curves for glucose-induced insulin secretion (half maximal insulin output 5.7
      mmol/l glucose vs 16.5 mmol/l glucose in shams) and glucose potentiation of
      arginine-induced insulin secretion (half maximal insulin output 3.5 mmol/l
      glucose vs 14.8 mmol/l glucose in shams). This heightened beta-cell sensitivity
      for glucose was not a result of the hyperglycaemia, because similarly reduced
      half-maximal insulin responses were found after a 60% pancreatectomy, a surgical
      procedure in which plasma glucose values remained normal. In summary, a rise in
      beta-cell sensitivity for glucose precedes the loss of glucose-induced insulin
      secretion in diabetic rats.

PMID- 8307251
TI  - Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced
      diabetic mice.
AB  - Multiple low doses of streptozotocin (LDS) induce low-incidence diabetes mellitus
      in Balb/cHan and high-incidence diabetes in CD-1 mice. We studied offspring of
      diabetic parents in both strains. Group 1 consisted of litters from control mice
      with no streptozotocin treatment. Group 2 litters had an LDS diabetic mother and
      a control father, group 3 litters had control mother with LDS diabetic father,
      and group 4 litters had both, LDS diabetic mother and father. Diabetes was
      induced by 5 x 40 mg streptozotocin per kg on five consecutive days. Progeny of
      diabetic mothers showed a state of reduced glucose tolerance associated with
      reduced glucose disappearance during intravenous glucose tolerance test and
      increased insulin secretion of isolated islets of Langerhans. These metabolic
      abnormalities predominated in the male litters of both strains of mice. Amniotic
      insulin was increased in diabetic mothers during pregnancy. No histologic
      abnormalities were observed in group 2 progeny. Pancreases in male offspring of
      LDS diabetic CD-1 fathers (group 3) were studied for insulitis. Insulitis was
      found in 40% of mice with normal glucose tolerance. A single subdiabetogenic dose
      of streptozotocin (40 mg/kg) induced insulitis in 90% of pancreases accompanied
      by reduced insulin release of isolated islets. By contrast, male Balb/cHan
      progeny of diabetic fathers failed to develop insulitis. In conclusion, we found
      (1) parental LDS diabetes was transmitted more often to male offspring, (2)
      maternal LDS diabetes was associated with hyperinsulin secretion and glucose
      intolerance in the offspring and (3) paternal LDS diabetes was accompanied by
      insulitis and insulin secretion deficiency in CD-1 progeny.

PMID- 8307252
TI  - The role of cytotoxic macrophages in non-obese diabetic mice: cytotoxicity
      against murine mastocytoma and beta-cell lines.
AB  - The cytotoxicity of macrophages from non-obese diabetic (NOD) mice against murine
      mastocytoma (P-815), and murine beta-cell lines having the NOD gene background
      (MIN6N-9a), were examined. Peritoneal exudate cells from 20-week-old mice showed
      higher cytotoxicity, measured as inhibition of thymidine uptake into P-815, than
      those from 12-week-old mice (p < 0.01). In cyclophosphamide-injected mice,
      cytotoxicity of peritoneal exudate cells had increased at 8 days post-injection,
      at which time the mice were not diabetic. To confirm macrophage cytotoxicity
      against pancreatic cells and examine its cytolytic mechanism, the cytotoxicity of
      peritoneal exudate cells from cyclophosphamide-injected NOD mice against MIN6N-9a
      cells was measured by the chromium release assay. These peritoneal exudate cells
      showed higher cytotoxicity as compared to those of saline-injected mice (p <
      0.001). Macrophages were demonstrated to be the major component of peritoneal
      exudate cells (50%) by flowcytometric analyses. Cytotoxicity increased with
      macrophage enrichment by adhesion (p < 0.01). Furthermore, a macrophage toxin,
      silica, completely blocked the cytotoxicity (p < 0.001). Cytokines (interleukin 1
      and tumour necrosis factor) and a nitric-oxide-producing vasodilator, sodium
      nitroprusside, were cytotoxic to MIN6N-9a cells but only sodium nitroprusside
      showed cytotoxicity when incubated for the same period as peritoneal exudate
      cells. Thus, macrophages play an important role in beta-cell destruction and
      soluble factors other than cytokines (e.g. nitric oxide) may be mediators of this
      early cytolytic process.

PMID- 8307253
TI  - Chronic overproduction of islet amyloid polypeptide/amylin in transgenic mice:
      lysosomal localization of human islet amyloid polypeptide and lack of marked
      hyperglycaemia or hyperinsulinaemia.
AB  - Type 2 (non-insulin-dependent) diabetes mellitus is characterised by
      hyperglycaemia, peripheral insulin resistance, impaired insulin secretion and
      pancreatic islet amyloid formation. The major constituent of islet amyloid is
      islet amyloid polypeptide (amylin). Islet amyloid polypeptide is synthesized by
      islet beta cells and co-secreted with insulin. The ability of islet amyloid
      polypeptide to form amyloid fibrils is related to its species-specific amino acid
      sequence. Islet amyloid associated with diabetes is only found in man, monkeys,
      cats and racoons. Pharmacological doses of islet amyloid polypeptide have been
      shown to inhibit insulin secretion as well as insulin action on peripheral
      tissues (insulin resistance). To examine the role of islet amyloid polypeptide in
      the pathogenesis of Type 2 diabetes, we have generated transgenic mice with the
      gene encoding either human islet amyloid polypeptide (which can form amyloid) or
      rat islet amyloid polypeptide, under control of an insulin promoter. Transgenic
      islet amyloid polypeptide mRNA was detected in the pancreas in all transgenic
      mice. Plasma islet amyloid polypeptide levels were significantly elevated (up to
      15-fold) in three out of five transgenic lines, but elevated glucose levels,
      hyperinsulinaemia and obesity were not observed. This suggests that insulin
      resistance is not induced by chronic hypersecretion of islet amyloid polypeptide.
      Islet amyloid polypeptide immunoreactivity was localized to beta-cell secretory
      granules in all mice. Islet amyloid polypeptide immunoreactivity in beta-cell
      lysosomes was seen only in mice with the human islet amyloid polypeptide gene, as
      in human beta cells, and might represent an initial step in intracellular
      formation of amyloid fibrils.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307254
TI  - Impaired blood flow and arterio-venous shunting in human diabetic neuropathy: a
      novel technique of nerve photography and fluorescein angiography.
AB  - New techniques of sural nerve photography and fluorescein angiography which are
      able to provide an index of nerve blood flow have been developed. Under local
      anaesthetic, 3 cm of sural nerve was exposed at the ankle using an operating
      microscope. Without disturbing the epineurium, vessels were identified and
      photographed at a standard magnification (x 30). These were independently graded
      by an ophthalmologist not otherwise involved with the study. Fluorescein
      angiography was then carried out on the exposed nerve. The fluorescein appearance
      time and intensity of fluorescence were quantified, using computer analysis of
      digitised images. Thirteen subjects with chronic sensory motor neuropathy, five
      non-neuropathic diabetic and nine normal control subjects were studied. The mean
      epineurial vessel pathology score of the neuropathic group was significantly
      higher than the combined normal control and non-neuropathic diabetic groups (p <
      0.01). Direct epineurial arteriovenous shunting was observed in six neuropathic
      and one non-neuropathic diabetic patients and not in any of the normal control
      subjects. The nerve fluorescein appearance time was significantly delayed in
      subjects with chronic sensory motor neuropathy (51.5 +/- 12 s) compared to both
      normal (34.7 +/- 9 s, p < 0.01) and non-neuropathic diabetic subjects (33.4 +/-
      11 s, p < 0.025). The mean intensity of fluorescence at 96, 252 and 576 s, was
      significantly lower in subjects with chronic sensory motor neuropathy compared
      with both of the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307255
TI  - Hyperinsulinaemia, dyslipidaemia and exaggerated adrenal androgen response to
      adrenocorticotropin in male smokers.
AB  - Insulin resistance and dyslipidaemia associated with smoking may result from
      increased secretion of anti-insulin hormones. We compared the pituitary
      adrenocortical function using oral glucose tolerance, dexamethasone suppression
      and ACTH stimulation tests in smoking (n = 22) and non-smoking (n = 22) healthy
      males matched for age, body mass index, and waist-to-hip ratio. Smokers had lower
      HDL-cholesterol (p < 0.02), and higher triglyceride (p < 0.001), basal cortisol
      (p < 0.05), insulin (p < 0.05), and C-peptide (p < 0.02) levels, and a higher
      response of insulin and C-peptide to oral glucose (p < 0.005) than non-smokers,
      while the ACTH, cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone, and
      androstenedione responses to oral glucose were similar in both groups. No
      differences were found in the response of cortisol, 17-hydroxyprogesterone,
      dehydroepiandrosterone, and androstenedione to dexamethasone. In contrast, the
      response of 17-hydroxyprogesterone (p = 0.04), dehydroepiandrosterone (p =
      0.007), and androstenedione (p = 0.001) to ACTH was higher in smokers than non
      smokers, while the increase in cortisol was of marginal significance (p = 0.07).
      In multiple regression analyses the dehydroepiandrosterone response to ACTH was a
      significant determinant of insulin, C-peptide, and triglyceride levels
      independent of physical activity, waist-to-hip ratio and HDL-cholesterol. Thus,
      smoking inhibits the adrenal 21-hydroxylase resulting in an increase in the
      production of adrenal androgens, which might contribute to the insulin resistance
      and dyslipidaemia in smokers.

PMID- 8307257
TI  - The development of hyperglycaemia in patients with insulin-resistant generalized
      lipoatrophic syndromes.
AB  - Insulin resistance is present in patients suffering from lipoatrophic syndromes
      long before the onset of diabetes mellitus. Thus, the decreased peripheral
      glucose disposal may not be the only mechanism of hyperglycaemia. The kinetic
      parameters of glucose homeostasis were evaluated in six young females aged 15,
      16, 18, 19 and 24 years with generalized lipoatrophy; one patient was studied
      both at 12 and 15 years. Insulin resistance was evaluated in vivo by the
      hyperinsulinaemic euglycaemic clamp (3-4 insulin infusion rates from 1 to 100
      mU/kg.min). All patients showed a rightward shift of the dose-response curve,
      indicating decreased insulin sensitivity. In two patients, maximal glucose
      disposal was moderately decreased, while in five patients it was dramatically
      reduced (3.6-6.9 mg/kg.min). Fasting plasma glucose was variable (4.3-18.3
      mmol/l) and did not correlate with peripheral glucose disposal rates. Hepatic
      glucose production, measured by infusion of [6,6-2H] glucose, varied from 1.7 to
      8.3 mg/kg.min and was significantly correlated with fasting plasma glucose. The
      overproduction of glucose despite basal hyperinsulinism suggested hepatic insulin
      resistance, which was confirmed by the abnormal response to constant unlabelled
      glucose infusion (2 mg/kg.min) in five patients. In conclusion, impaired glucose
      tolerance seems to develop in generalized lipoatrophy with aggravated peripheral
      insulin resistance. The present data show that fasting hyperglycaemia is mainly
      the consequence of increased hepatic glucose production.

PMID- 8307256
TI  - The epidemiology of diabetes mellitus in the United Kingdom: the Yorkshire
      Regional Childhood Diabetes Register.
AB  - A register of the incidence of Type 1 (insulin-dependent) diabetes mellitus in
      the Yorkshire region of the United Kingdom has been completed. A total of 1,490
      subjects aged between 0 and 16 years were identified from 1978 to 1990, giving an
      incidence of 13.7 per 100,000 (ages 0-14) or 13.6 per 100,000 (ages 0-16),
      comparable to other recent studies in the United Kingdom. An age-period-cohort
      analysis shows evidence for a modest drift effect of 1.75% per year (95%
      confidence interval 0.28 to 3.25%). There is a marked epidemic pattern with peaks
      at 4-year intervals. The age-incidence curve is similar to that reported
      elsewhere, having peaks in early childhood and puberty. Girls have an earlier
      pubertal peak than boys. There is substantial seasonal variation in incidence
      confined to those over 5 years of age. Ascertainment is believed to be very
      complete, and is estimated to be 97.6% (95% confidence interval 97.2% to 98.1%).

PMID- 8307258
TI  - Genetic risk factors in diabetic retinopathy.
AB  - Diabetic retinopathy is the leading cause of blindness in adults aged 30 to 65
      years. However, 20% of the diabetic population does not develop significant
      retinopathy. To examine the influence of immune-related genetic factors on the
      development of diabetic retinopathy, we studied immunoglobulin allotypes in 102
      subjects aged 8 to 20 years, who had had Type 1 (insulin-dependent) diabetes
      mellitus for 4.5 to 11 years (mean 7.3 years). HLA had been previously typed on
      59 of these subjects. Retinopathy was assessed by expert review of retinal
      photographs. Among the 44 patients who had evidence of retinopathy, 33(75%) were
      G2m(23+), while among the 58 patients without retinopathy but with similar
      duration of disease, only 28(48%) were G2m(23+) (p = 0.006). The HLA-DR types of
      patients with and without retinopathy were not significantly different. We
      conclude that there is significant evidence of an association between G2m(23) at
      the locus encoding IgG2 subclass heavy chains and susceptibility to the
      development of diabetic retinopathy early in the clinical course of the disease.
      Our findings provide important independent confirmation of a previous report of
      association between Gm allotypes and predisposition to diabetic retinopathy. We
      are unable to determine if the Gm effect on development of retinopathy is due to
      the G2m(23) allotype itself, or due to genes that are closely linked to, and in
      linkage disequilibrium with, the locus encoding the G2m(23) allotype.

PMID- 8307259
TI  - Human hexokinase II: localization of the polymorphic gene to chromosome 2.
AB  - Type 2 (non-insulin-dependent) diabetes mellitus is characterized by decreased
      levels of glucose 6-phosphate in skeletal muscle. It has been suggested that the
      lower concentrations of glucose 6-phosphate contribute to the defect in glucose
      metabolism noted in muscle tissue of subjects with Type 2 diabetes or subjects at
      increased risk of developing Type 2 diabetes. Lower levels of glucose 6-phosphate
      could be due to a defect in glucose uptake, or phosphorylation, or both.
      Hexokinase II is the isozyme of hexokinase that is expressed in skeletal muscle
      and is responsible for catalysing the phosphorylation of glucose in this tissue.
      The recent demonstration that mutations in another member of this family of
      glucose phosphorylating enzymes, glucokinase, can lead to the development of Type
      2 diabetes prompted us to begin to examine the possible role of hexokinase II in
      the development of this genetically heterogeneous disorder. As a first step, we
      have cloned the human hexokinase II gene (HK2) and mapped it to human chromosome
      2, band p13.1, by fluorescence in situ hybridization to metaphase chromosomes. In
      addition, we have identified and characterized a simple tandem repeat DNA
      polymorphism in HK2 and used this DNA polymorphism to localize this gene within
      the genetic linkage map of chromosome 2.

PMID- 8307261
TI  - Relationship between early metabolic control and the development of
      microalbuminuria--a longitudinal study in children with type 1 (insulin
      dependent) diabetes mellitus.
AB  - The cumulative incidence of microalbuminuria from onset up to 15 years of Type 1
      (insulin-dependent) diabetes mellitus and the relative importance of age,
      duration, blood pressure and metabolic control for subsequent microalbuminuria
      was studied in 156 children. Urinary albumin excretion and HbA1c were followed at
      3-month intervals from onset and systolic and diastolic blood pressure at the
      same interval from 5 years of diabetes. Persistent microalbuminuria over 20
      micrograms/min developed in 17 children. The cumulative incidence by duration was
      24.2% at 15 years of diabetes. Eleven patients developed microalbuminuria after
      more than 5 years. Among these, first 5-year mean HbA1c was 8.4 +/- 1.3% vs 7.2
      +/- 1.1% in normoalbuminuric children (p < 0.001). The crude relative risk of
      developing microalbuminuria with a first 5-year mean HbA1c greater than 7.5% was
      4.49 (95% confidence interval 1.13-17.84). The age- and duration-adjusted
      relative risk was 3.51% (0.90-14.42). The year before transition to
      microalbuminuria neither mean HbA1c nor yearly mean blood pressures, sex or age
      at onset of diabetes differed from normoalbuminuric children at the same diabetes
      duration. Age and duration were higher (p = 0.04). The relative importance of
      early vs later hyperglycaemia, yearly blood pressures, age, age at onset and
      duration of diabetes for increased albumin excretion rate after more than 5
      years, was shown in a multiple regression analysis where the first 5-year mean
      HbA1c was the only independent predictor (p = 0.02). Six patients had an onset of
      microalbuminuria before 5 years of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307260
TI  - Decline of mumps antibodies in type 1 (insulin-dependent) diabetic children and a
      plateau in the rising incidence of type 1 diabetes after introduction of the
      mumps-measles-rubella vaccine in Finland. Childhood Diabetes in Finland Study
      Group.
AB  - A nationwide mumps-measles-rubella vaccination was introduced in 1982 in Finland
      to children aged 1.5 to 6 years and since then mumps has virtually disappeared in
      the country. We investigated whether this rapid epidemiological change had any
      impact on antibody activity against mumps virus in Type 1 (insulin-dependent)
      diabetic children or on the incidence of Type 1 diabetes in Finland. Two case
      control series were collected before (series I and II) and three series after
      (series III-V) the introduction of the vaccination. IgA class mumps antibody
      levels were significantly higher in Type 1 diabetic children than in matched
      control children in the first two but not in the three later series. IgG class
      antibody levels were similar in patients and control subjects in the first two
      series but significantly lower in patients than in control subjects in the three
      later series. The overall incidence of Type 1 diabetes in 0-14-year-old children
      increased until 1987 but remained about the same during 1988-1990. In 5-9-year
      old children no further increase in Type 1 diabetes was seen since 1985, whereas
      in 0-4-year-old children the incidence continued to rise until 1990. The results
      suggest that the elimination of natural mumps by mumps-measles-rubella
      vaccination may have decreased the risk for Type 1 diabetes in Finland; a
      possible causal relationship is substantiated by the observed concomitant
      decrease in mumps antibody levels in diabetic children. However, further studies
      are required to determine if the vaccine virus, like natural mumps, could trigger
      the clinical onset of Type 1 diabetes in young children.

PMID- 8307262
TI  - Relation of birthweight to maternal plasma glucose and insulin concentrations
      during normal pregnancy.
AB  - Maternal diabetes mellitus is complicated by fetal macrosomia and predisposes the
      offspring to diabetes, but recent evidence indicates that a low, not high,
      birthweight is associated with a higher incidence of Type 2 (non-insulin
      dependent) diabetes in adult life. To clarify the relationships between maternal
      glucose and insulin levels and birthweight, we measured oral glucose tolerance
      and neonatal weight in a large group (n = 529) of women during the 26th week of
      pregnancy. Women with gestational diabetes (n = 17) had more familial diabetes,
      higher pre-pregnancy body weight, and tended to have large-for-gestational-age
      babies. In contrast, women with essential hypertension (n = 10) gave birth to
      significantly (p < 0.01) smaller babies. In the normal group (without gestational
      diabetes or hypertension, n = 503), maternal body weight before pregnancy and at
      term, maternal height, week of delivery, gender of the newborn, and parity were
      all significant, independent predictors of birthweight, together explaining 23%
      of the variability of neonatal weight. In addition, both fasting (p < 0.006) and
      2-h post-glucose (p = 0.03) maternal plasma glucose concentrations were
      positively associated with birthweight independent of the other physiological
      determinants, accounting, however, for only 10% of the explained variability. In
      a subgroup of 134 normal mothers with pre-pregnancy body mass index of less than
      25 kg.m-2, in whom plasma insulin measurements were available, the insulin area
      under-curve was inversely related to birthweight (p < 0.02) after simultaneously
      adjusting for physiological factors and glucose area.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8307263
TI  - Substrate specificity of proinsulin conversion in the constitutive pathway of
      transfected FAO (hepatoma) cells.
AB  - Proinsulin is usually targetted to the regulated secretory pathway of beta cells,
      and converted to insulin in beta granules. Under certain pathological situations,
      a significant amount of proinsulin becomes diverted to the constitutive pathway.
      To study the kinetics of proinsulin conversion in the constitutive pathway, FAO
      (hepatoma) cells, which secrete proteins uniquely via this pathway and not the
      regulated pathway, were stably transfected with cDNA encoding human, rat I or rat
      II proinsulin. Products released to the medium of transfected cells were analysed
      by reversed phase HPLC and radioimmunoassay. For human proinsulin, des 31,32
      split proinsulin (the conversion intermediate resulting from cleavage only at the
      B-chain/C-peptide junction followed by trimming of C-terminal basic residues by
      carboxypeptidase) was the only detectable conversion intermediate; for rat
      proinsulin II it was des 64,65 split proinsulin (cleaved and trimmed only at the
      C-peptide/A-chain junction); for rat proinsulin I, both intermediates were seen.
      Complete processing to insulin occurred for all three, but was most extensive for
      rat proinsulin I. When considered with the corresponding proinsulin sequences,
      these data show that a -4 basic residue (i.e. 4 residues N-terminal to the site
      of cleavage) facilitates proinsulin conversion in the constitutive pathway, and
      that arginine is preferred over lysine.

PMID- 8307265
TI  - [A new approach to plasma protein fractionation and production of highly purified
      blood preparations].

PMID- 8307264
TI  - Insulin resistance and insulin deficiency in the pathogenesis of type 2 (non
      insulin-dependent) diabetes mellitus: errors of metabolism or of methods?

PMID- 8307266
TI  - [Infusion therapy of experimental hemorrhagic shock using the antihypoxic drug
      oliphen].
AB  - The authors studied the potential of an antihypoxic drug oliphen in raising the
      efficacy of hemorrhagic shock treatment with sodium chloride isotonic solution.
      The severity of the shock and the efficacy of treatment were evaluated by
      parameters of central hemodynamics, microcirculation, oxygen regimen and acid
      base condition. Dog and white rat experiments showed that the addition of oliphen
      to solution treatment produced better results than sodium chloride solution
      alone.

PMID- 8307267
TI  - [Effectiveness of oxygen delivery to tissues during complete replacement of blood
      by bovine polyhemoglobin].
AB  - The study has been performed to test the hypothesis on feasibility of omitting
      pyridoxylation in production of bovine polyhemoglobin as compared to
      polyhemoglobin from human red cells. The model of a complete replacement of
      rabbit blood for polyglucin (Het approximately 2%) was used to compare efficacy
      characteristics for O2 delivery to tissues upon introduction of bovine
      polyhemoglobin against rabbit red cells. Immediately after the replacement, O2
      release efficacy and that of circulation were identical, whereas 30 and 60 min
      after it, developing decompensation of hemodynamics indicated inability of bovine
      heterohemoglobin, unlike own red cells, to increase A-B difference by oxygen,
      probably due to metform rise.

PMID- 8307268
TI  - [Combined plasmaleukapheresis in donors immunized with staphylococcal anatoxin].

PMID- 8307269
TI  - [Radiologic diagnosis of non-Hodgkin's lymphoma in abdominal and retroperitoneal
      sites].
AB  - A total of 112 patients with non-Hodgkin's lymphomas of abdominal and
      retroperitoneal localization were examined by the ultrasonic and x-ray methods,
      in 83 of them x-ray computer-aided tomography was used. Angiographic examinations
      and puncture biopsy monitored by US or x-ray CAT were carried out if indicated.
      The authors discuss the problems of ultrasonic and x-ray semeiotics of the
      lymphomatous involvement of the lymph nodes, spleen, gastrointestinal tract. They
      claim that USE, permitting the specification of further plan of examination of
      each patient, and x-ray examination as a method to assess the gastrointestinal
      status are the optimal methods for the primary diagnosis of non-Hodgkin's
      lymphomas. US data may prompt further application of x-ray CAT, whose results
      will supplement the US findings. Angiographic examinations should be carried out
      only in the most difficult diagnostic situations, bearing in mind the invasive
      nature of the method and its high price.

PMID- 8307270
TI  - [Possibilities of individual functional diagnosis, therapy, and prognosis in
      hemoblastosis].
AB  - The authors propose a combined methodological approach enabling physicians to
      measure in hours the duration of the regeneration cycle and its periods without
      introduction of the tracers. The method has been tried on dogs with spontaneous
      lymphoblastic lymphosarcomas. It is believed feasible to make individual
      functional diagnosis, design of treatment policy and prognosis. The procedure is
      recommended for clinical trials.

PMID- 8307271
TI  - [Submicroscopic features of cells in the microenvironment of hematopoietic
      development of virus-induced Rauscher leukemia].
AB  - The study was made of submicroscopic changes in the cells of bone marrow and
      splenic microenvironment in mice developing virus-induced Rauscher leukemia. As
      shown by electron microscopy, ultrastructural cytochemistry and
      immunocytochemistry, ultrastructure of the complexes from the stromal and
      hemopoietic cells underwent noticeable alterations as early as the first days
      after the virus introduction. This suggests that bone marrow is the primary
      target of the virus in Rauscher leukemia. Affections of the macrophages,
      dendrite, interdigital and lymphoid cells of the spleen reflect their
      participation in the body defenses against the virus. Progressive shift of
      erythropoiesis from the bone marrow into the spleen is related to
      morphofunctional changes in the microenvironmental cells. The findings may be
      useful in consideration of cellular pathogenetic aspects of acute leukemia.

PMID- 8307272
TI  - [Pathogenetic aspects of treatment of aplastic anemia].

PMID- 8307273
TI  - [Effect of basic plasma polypeptides on the process of blood coagulation and
      fibrinolysis].
AB  - An original method was used to isolate polypeptides from citrate platelet-free
      plasma of healthy subjects. These polypeptides were able to prolong
      recalcification, kaolin, kaolin-cephalin and prothrombin plasma time, sharply
      reduce thrombin time of standard and heparinized plasma, to inhibit fibrin self
      building and stimulate fibrinolytic activity of blood. An antiheparin effect of
      polypeptides in adequate doses is similar to that of protamine sulfate.
      Polypeptide antiheparin plasma factor has molecular mass about 2000 D, its
      chromatographic profile coincides with that of protamine sulfate.

PMID- 8307274
TI  - [Local hemostatic drugs].
AB  - The paper summarizes the data available on utilization of drugs diverse by
      chemical structure and mechanism of action for local arrest of capillary
      parenchymal hemorrhages. Basic drugs in the field are listed with indication of
      their drawbacks. Further efforts should be directed to management of these side
      effects.

PMID- 8307275
TI  - [Distribution of immunogenetic markers of erythrocyte systems in ischemic heart
      disease].
AB  - Distribution of 24 phenotypes of 6 red cell systems (ABO, Rh-Hr, MNSs, Duffy,
      Kell-Chellano, Kidd) has been studied for the first time in 275 coronary patients
      of Armenian nationality. Antigens ABO and MN were determined by hemagglutination,
      antigen Rho(D) by conglutination, antigens C, c, E, e, Fya, Fyb, Jka, Jkb, K and
      k by indirect Coombs reaction. Out of the 6 systems, only heterozygous phenotype
      Cc and homozygous phenotype Jk (a-b+) were positively associated with coronary
      heart disease. The carriers of the former had a risk of CHD 2.2-times that for
      patients carrying CC and Jk (a+b+), while the carriers of the latter had this
      risk increased 5-fold. Simultaneous identification of Kidd system phenotypes and
      Rh-Hr (Jkb (a-b+) and CC in the same patient may be considered as a genetic CHD
      marker in Armenian population. The above fact needs special attention in early
      preclinical diagnosis and prevention of CHD.

PMID- 8307276
TI  - [Role of the liver in immunobiologic regulation of homeostasis].

PMID- 8307277
TI  - [Enhanced osteogenesis in severe aplastic anemia].
AB  - Histologic specimens of the bone marrow were obtained from healthy subjects and
      aplastic anemia (AA) ones. Comparison of the histomorphometry was indicative of
      an increase in spongy bone tissue and in the number of osteoid cells in AA. This
      indirectly suggested enhanced proliferative activity of osteogenic precursors and
      osteosynthesis in AA. Interrelationship is probable between osteogenesis and
      hemopoiesis.

PMID- 8307278
TI  - [A case of anti-Kell allosensitization in high titer resulting from a single
      blood transfusion].

PMID- 8307279
TI  - [Is it advisable to inject novocaine solution intra-articularly during invasive
      therapy of hemarthrosis in patients with hemophilia?].

PMID- 8307280
TI  - [Comparative study of the quality of domestic albumin solution and foreign
      analogs].
AB  - The quality and standards of albumin solutions (5, 10 and 20%) made in this
      country meet the requirements of national specification documentation. This,
      however, lacks some standards included into European Pharmacopoeia and mandatory
      for foreign manufacturers (Na and K ions, hemipigments, polymers,
      thermostability). The comparative tests of the albumin solutions made in Russia
      and abroad by conventional European standards showed that Russian solutions by
      some parameters are inferior to foreign samples. This urges improvement of the
      solution production technology as well as updating technical documents regulating
      the product quality.

PMID- 8307281
TI  - [Treatment of lymphosarcoma with onkaspar (PEG-L-asparaginase) in combination
      with other drugs].

PMID- 8307282
TI  - [Diagnostic potential of ultrasound methods of studying the lymph nodes and
      indirect lymphoscintigraphy in lymphoproliferative diseases].
AB  - Ultrasonic and radionuclide investigations of the lymph nodes have been performed
      in 342 patients with malignant lymphoproliferative diseases. A comparative
      analysis of the data obtained by sonography and indirect lymphoscintigraphy has
      specified diagnostic spectrum of these procedures. The accuracy and specificity
      of sonography and broad-scale visualization secured by it dictate primary usage
      of the procedure as a screening test in initial examinations and as a control
      sensitive estimator of the on-going treatment efficacy. Indirect
      lymphoscintigraphy is recommended as an adjuvant to echography for detailing
      topics and nature of the lymph node lesion and to assess the process above the
      diaphragm. Frequency and regimen of the examinations should be based on clinical
      demands.

PMID- 8307283
TI  - [Sonographic and histomorphologic parallels in various histologic variants of
      chronic myeloid leukemia].
AB  - Histomorphometric findings at the study of marrow puncture specimens were
      compared to sonographic picture of the liver and spleen in 20 myeloid leukemia
      chronic. Histomorphometric and sonographic changes observed showed parallel
      pathological processes in the hemopoietic micro-surroundings and in the liver,
      spleen. Sonography proved able to considerably broaden diagnostic armory of the
      physician, to prognosticate leukemia outcomes, thus suggesting a differential
      approach to the disease treatment.

PMID- 8307284
TI  - [Status of the pool of hematopoietic stem cells in the peripheral blood in
      patients with lung cancer before and during polychemotherapy].
AB  - The pool of hematopoietic cells-precursors from the peripheral blood of patients
      with lung cancer stage III-IV was characterized by reduced number of circulating
      cells-precursors of granulomonocyto-(CFU-GM) and erythropoiesis (CFU-E). In the
      course of antitumor chemotherapy the counts of CFU-GM and CFU-E diminished 2 and
      4-fold, respectively. The prednisolone functional test determined that depletion
      of CFU-GM and CFU-E pools in the peripheral blood was preceded with lowered pool
      reserve for hematopoietic precursors.

PMID- 8307285
TI  - [Lectin-induced aggregation of neutrophilic granulocytes before and after
      irradiation of the blood with a helium-neon laser].
AB  - To clarify the changes in cellular reactivity in response to single irradiation
      of blood with He-Ne laser, the authors studied neutrophil aggregation and
      neutrophil ATP release induced by stimulation with lectins diverse in
      carbohydrate specificity. Blood samples from 30 healthy donors were investigated
      using PICA lumoaggregometer (Chrono-Log Corporation, USA) and concanavalin A, PHA
      L, WGA, SBA as aggregation inductors. He-Ne laser radiation in most cases results
      in reduced neutrophil capacity for aggregation. Nevertheless, it activates ATP
      release under stimulation with lectins of various carbohydrate specificity. It
      follows that mechanisms of lectin-induced reactions, aggregation of neutrophils
      and ATP release, are different.

PMID- 8307286
TI  - [Stromal lipids of peripheral blood erythrocytes and myocardial dystrophy in
      patients with iron deficiency anemia].
AB  - Lipid fractions (total lipids and phospholipids, triglycerides, free fatty acids,
      cholesterol, lysophospholipids, sphingomyelins, phosphatidylserines,
      phosphatidylcholines, phosphatidylethanolamines, cardiolipins, phosphatidic
      acids) were assessed in stromal red cells of 41 patients with iron deficiency
      anemia (IDA). The values obtained were correlated with wave T height at rest ECG.
      It was found that IDA patients have abnormalities in the lipid spectrum of red
      cell stroma promoting myocardiodystrophy. Therapeutic measures to normalize
      relevant lipid spectrum may become one of the factors preventing further
      dystrophic developments in the myocardium.

PMID- 8307287
TI  - [Monoclonal antibodies against D-antigen of the rhesus system].
AB  - The authors review current data on the production and characterization of anti-D
      monoclonal antibodies. The main methods for establishment of anti-D antibody
      secreting cell lines are considered: EBV-transformation of B lymphocytes from
      immune donor and hybridization with malignant human or murine cell lines.
      Serologic and immunological properties of anti-D monoclonal reagents for blood
      group Rh-typing as well as feasibility of using anti-D monoclonal antibodies as a
      modality against hemolytic disease of the newborn are discussed.

PMID- 8307288
TI  - [Phospholipid and glycerol levels in women's erythrocytes depending on body iron
      reserves].
AB  - Red cell phospholipids and glycerols were measured in 18 normal by peripheral
      blood hemoglobin, 19 iron deficient (latent deficiency) and in 20 hypoferric
      anemia females. Latent and manifest iron deficiency caused a pronounced elevation
      in the levels of glycerols, lysophosphatidylinositols, lysophosphatidylcholines,
      lysophosphatidylethanolamines, phosphatidylinositol diphosphates and a drop in
      the phosphatidylserines in erythrocytes. This provokes serious structural and
      functional alterations in erythrocytic membranes of iron deficient subjects.

PMID- 8307290
TI  - [Interaction of prothrombin with erythrocytes and alveolar macrophages].
AB  - A study was made of porcine 125I-prothrombin interaction with red cells and
      alveolar macrophages in the presence of CaCl2 or EDTA. Prothrombin binding with
      red cells was similar to that to alveolar macrophages (Kd = 3.7 x 10(-6) M and
      1.9 x 10(-6) M, respectively). These parameters did not depend on the presence of
      Ca2+ ions in the medium. Red cell hemolysis led to diminished affinity of
      prothrombin to blood ghost surfaces.

PMID- 8307289
TI  - [A comprehensive radioisotope assessment of the effectiveness of Ferrum Lek in
      patients with iron-deficiency anemia].
AB  - Before and after treatment iron metabolism was evaluated in 37 iron deficient
      women given intravenous Ferrum Lek. In addition to standard blood counts and
      serum iron tests, iron metabolism was investigated with Fe-59 whole body
      radiometry in a low-background camera. The treatment effect was assessed in 1.3
      and 6 months. The red blood cells and iron content in the serum returned to
      normal values. The effect persisted for 6 months. The initial 3 months iron
      accumulated in the depot, being further distributed in the blood. Total body iron
      6 months after the treatment was at the baseline levels. It is thought adequate
      to use Ferrum Lek in the management of women with iron deficiency anemia.

PMID- 8307291
TI  - [Distribution of alpha-thalassemia in children in Uzbekistan].

PMID- 8307292
TI  - [Immune status of people participating in the clean-up of after-effects of the
      Chernobyl Nuclear Power Plant accident living in the industrial region of
      Donbass].
AB  - The examination of 286 subjects exposed to radiation hazards when taking part in
      liquidation of the Chernobyl accident aftereffects was performed to compare
      persons living under ecologically unfavourable conditions (significant air
      pollution due to heavy industry) against those living in relatively comfortable
      environment. It was found that immune status of the former displayed imbalance.
      In the latter immunity was much less damaged. The findings suggest a conclusion
      on the role of environmental factors in immunological disturbances in subjects
      exposed to small doses of ionizing radiation.

PMID- 8307293
TI  - [Effect of plasma stabilizers on fibronectin properties during storage].

PMID- 8307294
TI  - [An attempt to use the Ommaya reservoir to treat recurrent neuroleukemia].

PMID- 8307295
TI  - [Potential of hematopoietic stem cells marked with retrovirus: dependence on
      stimulation with growth factors].
AB  - Lethally irradiated mice were reconstituted with hematopoietic cells retrovirally
      marked by human ADA sequence. Before and during gene transfer adult bone marrow
      cells were pre-stimulated by a combination of exogenous growth factors, IL-6 and
      kit-ligand, or by culture on irradiated adherent cell layer of long-term bone
      marrow culture. Twelve-day-old embryonic liver cells were transduced without
      prestimulation with exogenous growth factors. In mice reconstituted with growth
      factors stimulated adult bone marrow cells during 4 months after transplantation
      200-300 hematopoietic cell clones were functioning simultaneously. Five months
      and later after reconstitution oligo-monoclonal hematopoiesis was revealed. The
      findings suggest that growth factors induce long-lasting proliferation of
      quiescent pHSC as a result of which clone(s) with proliferative advantage replace
      all others and only this clone(s) persists during long time, up to 11 months.
      Vice versa, in mice reconstituted with adult or embryonic hematopoietic cells
      which were transduced without growth factors prestimulation, the phase of
      polyclonal hematopoiesis was never observed and hematopoietic cell clonal
      succession was revealed. The data obtained for the first time demonstrate
      artifactual influence of high-concentration IL-6 and kit-ligand on the
      developmental potential of hematopoietic stem cell. The model can be useful for
      the study of mechanism of hematopoiesis regulation, proliferative and
      developmental potential of primitive HSC and growth factors effect on them.

PMID- 8307296
TI  - [Pathogenetic mechanisms in the onset of infectious complications in chronic
      myeloid leukemia].
AB  - Out of 177 patients with advanced chronic myeloid leukemia infectious
      complications developed in 23.66%. The chief reason for emergence of bacterial
      processes in chronic myeloid leukemia is attributed to qualitative and
      quantitative insufficiency of phagocytizing and immunocompetent cells provoking
      disturbance of cooperative interaction between lymphocytes and neutrophils.

PMID- 8307297
TI  - [Possible relationship between the cytologic characteristics of mouse leukemia P
      388 cells and their sensitivity to rubomycin].
AB  - In search for markers of tumor cell resistance to cytostatic drugs, cytologic
      characteristics were compared of resistant and sensitive to rubomycin variants of
      mouse P-388 leukemia. Morphocytochemical, morphometrical and cytogenetic
      investigations were performed as well as measurements of intracellular pH. As
      shown by the fluorescent test, pH levels in rubomycin-sensitive and resistant
      subpopulations differed. This fact evidences an important role of intracellular
      pH in inducing the resistance and revealed some mechanisms of rubomycin-resistant
      tumor cell selection.

PMID- 8307298
TI  - [Vesiculation and change of erythrocyte membrane proteins in storage of preserved
      blood and erythrocyte mass at 4 degrees C].
AB  - Erythrocyte vesiculation and changes in membrane protein composition during
      storage of blood and red cell concentrates in solution "Glugicir" at 4 +/- 2
      degrees C have been studied. It is shown that the main part of vesicles is
      shedding after 9 days of storage. This process corresponds to a decrease of
      protein 3 and to polyphase changes of membrane-bound hemoglobin as is shown by
      gel-electrophoresis. During 9-day storage, when erythrocyte ATP is constant and
      the vesicle shedding is small, an increase in membrane-bound hemoglobin and a
      decrease of spectrin in isolated membranes take place. The above changes are not
      the result of oxidative processes in membrane lipid bilayer or in hemoglobin.
      There was also protein destruction in membranes of stored erythrocytes. It is
      suggested that in stored blood two type of erythrocyte vesiculation take place:
      one is due to cell senescence, the other results from metabolic depletion.

PMID- 8307299
TI  - [Effect of total laser irradiation on migration of mature cells in rat bone
      marrow].
AB  - In experiment on 50 white Wistar male rats, total laser radiation was assessed as
      regards its effect on bone marrow structure and cells migration into the blood
      and small intestinal mucosa. The unit "ILGI-101" was used on the basis of copper
      laser for a single radiation procedure. As shown by light and electron
      microscopy, morphometry, copper laser single total irradiation causes material
      changes in the bone marrow and peripheral blood of rats. These were most
      pronounced 1 hour after the irradiation and depended on the cell migration into
      the small intestinal stroma. 24 hours after the procedure morphological structure
      of intestinal bone marrow showed a tendency to normalization.

PMID- 8307300
TI  - [Hemodilution coagulopathy and infusion-transfusion therapy of massive hemorrhage
      in obstetric practice].
AB  - The paper presents the experience gained by a critical hematological care team in
      diagnosis and treatment of hemodilution coagulopathy. The investigations were
      performed in Leningrad obstetric hospitals in 1985-1990 and included 38 patients.
      Basic principles of the therapy and its control are described. The policy of
      infusion-transfusion treatment indicated in the paper secured successful
      management of puerpera with massive blood loss.

PMID- 8307301
TI  - [Intravenous dalargin as a method of increasing the effectiveness of blood
      reinfusion in the late stages of hemorrhagic shock].
AB  - Acute experiments on 63 adult rabbits have shown that acute divided blood loss
      for 5 min (27 +/- 1% of the whole blood volume) results in the development of
      reversible hemorrhagic shock with survival of all the animals. In the same volume
      of continuous blood exfusion (27 +/- 5% of blood volume) or an increase in blood
      loss to 43 +/- 2% of blood volume hemorrhagic shock proved irreversible. Early
      reinfusion of heparinized blood saved all the animals, whereas late reinfusions
      only prolonged the survival. Intravenous administration of dalargin (0.1 mg/kg)
      in late shock was not effective and all the animals died. Dalargin introduction
      after blood reinfusion in late shock saved the animals lives. The conclusion is
      made on benefits of intravenous dalargin for raising the efficacy of reinfusions
      (hemotransfusion) at late stages of severe hemorrhagic shock.

PMID- 8307302
TI  - [Role of alpha-interferon in the treatment of hairy cell leukemia].
AB  - Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder that is
      characterized clinically by splenomegaly, pancytopenia, and the presence of
      malignant tartrate-resistant acid phosphatase (TRAP)-positive lymphocytes
      displaying unique morphological features in the peripheral blood and bone marrow.
      In the past, splenectomy has been the mainstay of treatment, resulting in
      symptomatic palliation and hematological improvement in 90 percent of patients.
      However, most patients undergoing splenectomy eventually require additional
      therapy; hematologic parameters and the degree of bone marrow cellularity are now
      utilized to identify to identify subsets of patients who might derive long-term
      benefit from the procedure. 2'-Deoxycoformycin (DCF) and 2-chlorodeoxyadenosine
      (2-cda) are experimental agents that have demonstrated curative potential in HCL;
      however, unresolved concerns about the long-term toxicity of DCF currently
      preclude its routine use, and further studies are required to define the toxicity
      and duration of responses obtained with 2-cda. As a result, alpha-interferon
      (alpha IFN) presently represents the treatment of choice for most patients with
      HCL. While alpha IFN has not been shown to cure HCL, its advantages include a
      high rate of response, a favorable side effect profile, its ability to be used
      safely in patients with active infections, and its ability to re-induce remission
      in relapsing patients. The mechanisms underlying alpha IFN's effectiveness seem
      to involve its immunomodulatory actions, which decrease the frequency of
      infectious complications in the early stages of therapy, and its ability to
      induce hairy cells to differentiate into more mature cells less responsive to
      proliferative signals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307303
TI  - [Reactive changes in hemopoiesis in hymenolepiasis].
AB  - Signs of hypoplastic anemia in experimental hymenolepiasis become manifest when
      immature cestodes develop and gain severity at the stage of mature cestodes.
      Phagocytic activity of neutrophils acquires an undulating pattern.
      Dehelminthization of mice with fenasal (1000 mg/kg/day) or asinox (75 mg/kg,
      daily) made hypoplastic processes in the bone marrow reversible and precluded
      routine undulation of phagocytosis.

PMID- 8307304
TI  - [Plasma lipid spectrum in acute leukemia].
AB  - The examination of 54 patients with acute leukemia (AL) found out ambiguous
      changes in plasmic lipid spectrum typical for elderly patients.
      Hypocholesterolemia occurred more frequently in nonlymphoblastic AL, is
      accompanied with severe anemia and infectious-septic complications.
      Hyperlipidemia was more common among senile AL patients with coronary heart
      disease which contributed to circulatory failure, cardiac arrhythmia, pneumonia
      complications and eventually to shorter survival of AL patients.

PMID- 8307306
TI  - [Multi-aberrant cells: phenomenon, reality and outlook for research progress].

PMID- 8307305
TI  - [Cytochemical lymphocytic markers as criteria suitable for mass and selective
      hematologic screening of children living in areas contaminated by radionuclides].
AB  - A cytochemical lymphocytogram by PAS--reaction and nonspecific esterase test was
      made using blood smears from 820 children living in different regions of the
      Bryansk area exposed to radioactive contamination and from 46 matched controls
      from noncontaminated territories. Most of the children were born before the
      Chernobyl accident. The cytochemical lymphocytogram was informative enough to
      evaluate lymphocytic pool and its renewal. The lymphocytogram parameters served
      criteria for selection of children's groups at relative risk. The groups
      comprised 25-60% of the examinees depending on the contamination degree and were
      registered for subsequent follow-up and rehabilitation.

PMID- 8307307
TI  - Rogue cells: possible future studies.

PMID- 8307308
TI  - [Multiple chromosome aberrations--realization of a programmed reaction of the
      genome of specialized cell subpopulations to various stressors].

PMID- 8307309
TI  - [Detection of multi-aberrant lymphocytes in cytogenetic examination of various
      groups of people in contact with mutagenic factors].

PMID- 8307311
TI  - [Irradiation as one of the possible causes of emergence of multi-aberrant cells
      in human populations].

PMID- 8307310
TI  - [Multi-aberrant cells in people undergoing radiation exposure].

PMID- 8307312
TI  - [Detection of multi-aberrant cells in miners of the Tselinograd district].

PMID- 8307313
TI  - [Neutrophil function in clinical medicine. I. Neutrophil migration].

PMID- 8307314
TI  - [Kinetics of circulating mature granulocytes and blast cells in hemoblastosis
      (experimental study)].

PMID- 8307315
TI  - [Toxic-allergic uveitis as a complication in hydrolysin infusion].

PMID- 8307316
TI  - [A casuistic case of DIC syndrome].

PMID- 8307317
TI  - [Bone marrow transplantation in thalassemia].
AB  - Thalassemia major is a progressive disease. Modern therapy with transfusions and
      iron chelation has greatly improved both the quality and length of thalassemics
      life. Nevertheless, progressive overload of iron in the organs, hepatitis and
      other infections acquired randomly imply the risk of mortality that increases
      with age. Bone marrow transplant from an HLA identical donor (a possibility for
      about 45%) represents the only form of radical cure of the disease. With the
      classification of the classes of risk we know today that a thalassemic child has
      a chance to die from transplant 3 to 100 with probability of being cured 94%.
      Thalassemics that receive the transplant at a more advanced stage of
      complications of the disease have a major risk of death due to the transplant of
      class 2 (14% probability of death due to the transplant against 83% chance of
      being cured). Class 43 patients have 9 chances out of 100 to die of transplant
      and 60% probability of being cured of thalassemia.

PMID- 8307318
TI  - Longevity-determining genes in Caenorhabditis elegans: chromosomal mapping of
      multiple noninteractive loci.
AB  - We have used chromosome mapping with polymorphic markers to define genetic
      components governing life span in the nematode Caenorhabditis elegans. A complex
      recombinant-inbred population was derived from an interstrain cross, yielding >
      1000 genotypes, each a composite of homozygous segments from the two parental
      strains. Genotypes were analyzed for the last-surviving 1-5% of worms in aging
      cohorts, and for young controls, by multiplex polymerase chain reaction using
      polymorphic markers to distinguish the parental alleles. We identified five
      regions of the genome at which one parental allele was significantly enriched in
      long-lived subpopulations. At four of five loci, the same alleles were selected
      in aging cohorts maintained under two different conditions, implying that these
      genes determine life span in differing environments.

PMID- 8307319
TI  - Suppressors of glp-1, a gene required for cell communication during development
      in Caenorhabditis elegans, define a set of interacting genes.
AB  - The glp-1 gene is essential for two cell interactions that control cell fate in
      Caenorhabditis elegans: induction of anterior pharynx in the embryo and induction
      of mitotic proliferation in the germ line. To identify other genes involved in
      these cell interactions, we have isolated suppressors of two temperature
      sensitive alleles of glp-1. Each of 14 recessive suppressors rescues both
      embryonic and germline glp-1(ts) defects. These suppressors are extragenic and
      define a set of six genes designated sog, for suppressor of glp-1. Suppression of
      glp-1 is the only obvious phenotype associated with sog mutations. Mutations in
      different sog genes show allele-specific intergenic noncomplementation,
      suggesting that the sog gene products may interact. In addition, we have analyzed
      a semidominant mutation that suppresses only the glp-1 germline phenotype and has
      a conditional feminized phenotype of its own. None of the suppressors rescues a
      glp-1 null mutation and therefore they do not bypass a requirement for glp-1.
      Distal tip cell function remains necessary for germline proliferation in
      suppressed animals. These suppressor mutations identify genes that may encode
      other components of the glp-1 mediated cell-signaling pathway or regulate glp-1
      expression.

PMID- 8307320
TI  - Intragenic dominant suppressors of glp-1, a gene essential for cell-signaling in
      Caenorhabditis elegans, support a role for cdc10/SWI6/ankyrin motifs in GLP-1
      function.
AB  - The glp-1 gene product mediates cell-cell interactions required for cell fate
      specification during development in Caenorhabditis elegans. To identify genes
      that interact with glp-1, we screened for dominant suppressors of two temperature
      sensitive glp-1 alleles and recovered 18 mutations that suppress both germline
      and embryonic glp-1 phenotypes. These dominant suppressors are tightly linked to
      glp-1 and do not bypass the requirement for a distal tip cell, which is thought
      to be the source of a signal that is received and transduced by the GLP-1
      protein. Using single-strand conformation polymorphism (SSCP) analysis and DNA
      sequencing, we found that at least 17 suppressors are second-site intragenic
      revertants. The suppressors, like the original glp-1(ts) mutations, are all
      located in the cdc10/SWI6/ankyrin domain of GLP-1. cdc10/SWI6/ankyrin motifs have
      been shown to mediate specific protein-protein interactions in other
      polypeptides. We propose that the glp-1(ts) mutations disrupt contact between GLP
      1 and an as yet unidentified target protein(s) and that the dominant suppressor
      mutations restore appropriate protein-protein interactions.

PMID- 8307321
TI  - Analysis of mutations in the sqt-1 and rol-6 collagen genes of Caenorhabditis
      elegans.
AB  - Different mutations in the sqt-1 and rol-6 collagen genes of Caenorhabditis
      elegans can cause diverse changes in body morphology and display different
      genetic attributes. We have determined the nucleotide alterations in 15 mutant
      alleles of these genes. Three mutations in sqt-1 and one in rol-6 that cause
      dominant right-handed helical twisting (RRol) of animals are arginine to cysteine
      replacements. These mutations are all within a short conserved sequence, on the
      amino terminal side of the Gly-X-Y repeats, that is found in all C. elegans
      cuticle collagens. A recessive RRol mutation of rol-6 is a replacement of one of
      the same conserved arginines by histidine. In contrast, three sqt-1 mutations
      that cause recessive left-handed helical twisting (LRol) are replacements of a
      conserved carboxy-terminal cysteine residue with either tyrosine or serine. These
      results suggest that disulfide bonding is important in collagen organization and
      that a deficit or surplus of disulfides may cause cuticle alterations of opposite
      handedness. In contrast to other collagens, glycine replacement mutations in the
      Gly-X-Y repeats of sqt-1 cause very mild phenotypes. Nonsense mutations of both
      sqt-1 and rol-6 cause nearly, but not totally, wild-type phenotypes. A nonsense
      mutation in sqt-1 suppresses the phenotype of rol-6 RRol mutations, suggesting
      that rol-6 collagen function is dependent on the presence of sqt-1 collagen.
      Mutations of sqt-1 are not suppressed by a rol-6 nonsense mutation, however,
      indicating that sqt-1 collagen can function independently of rol-6.

PMID- 8307322
TI  - Segmental polarity in Drosophila melanogaster: genetic dissection of fused in a
      Suppressor of fused background reveals interaction with costal-2.
AB  - fused (fu) is a segment polarity gene that encodes a putative serine/threonine
      kinase. A complete suppressor of the embryonic and adult phenotypes of fu
      mutants, Suppressor of fused (Su(fu)), was previously described. The amorphic
      Su(fu) mutation is viable and displays no phenotype by itself. We have used this
      suppressor as a tool to perform a genetic dissection of the fu gene. Analysis of
      the interaction between Su(fu) and 33 fu alleles shows that they belong to three
      different classes. Defects due to class I fu alleles are fully suppressed by
      Su(fu). Class II fu alleles lead to a new segment polarity phenotype in
      interaction with Su(fu). This phenotype corresponds to embryonic and adult
      anomalies similar to those displayed by the segment polarity mutant costal-2 (cos
      2). Class II alleles are recessive to class I alleles in a
      fu[I]/fu[II];Su(fu)/Su(fu) combination. Class 0 alleles, like class I alleles,
      confer a normal segmentation phenotype in interaction with Su(fu). However class
      II alleles are dominant over class 0 alleles in a fu[0]/fu[II];Su(fu)/Su(fu)
      combination. Alleles of class I and II correspond to small molecular events,
      which may leave part of the Fu protein intact. On the contrary, class 0 alleles
      correspond to large deletions. Several class I and class II fu mutations have
      been mapped, and three mutant alleles were sequenced. These data suggest that
      class I mutations affect the catalytic domain of the putative Fu kinase and leave
      the carboxy terminal domain intact, whereas predicted class II proteins have an
      abnormal carboxy terminal domain. Su(fu) enhances the cos-2 phenotype and cos-2
      mutations interact with fu in a way similar to Su(fu). All together these results
      suggest that a close relationship might exist between fu, Su(fu) and cos-2
      throughout development. We thus propose a model where the Fu+ kinase is a
      posterior inhibitor of Costal-2+ while Su(fu)+ is an activator of Costal-2+. The
      expression pattern of wingless and engrailed in fu and fu;Su(fu) embryos is in
      accordance with this interpretation.

PMID- 8307323
TI  - hobo enhancer trapping mutagenesis in Drosophila reveals an insertion specificity
      different from P elements.
AB  - P element enhancer trapping has become an indispensable tool in the analysis of
      the Drosophila melanogaster genome. However, there is great variation in the
      mutability of loci by these elements such that some loci are relatively
      refractory to insertion. We have developed the hobo transposable element for use
      in enhancer trapping and we describe the results of a hobo enhancer trap screen.
      In addition, we present evidence that a hobo enhancer trap element has a pattern
      of insertion into the genome that is different from the distribution of P
      elements in the available database. Hence, hobo insertion may facilitate access
      to genes resistant to P element insertion.

PMID- 8307324
TI  - A new biological rhythm mutant of Drosophila melanogaster that identifies a gene
      with an essential embryonic function.
AB  - To identify components of a circadian pacemaker output pathway, we have sought
      Drosophila mutations that alter the timing of eclosion but do not perturb
      circadian period or the expression of the activity rhythm. A mutant named lark
      has been identified, for which daily peaks of eclosion occur abnormally early
      while populations are synchronized to either light/dark or temperature cycles.
      The temporal phasing of locomotor activity in lark mutants, however, is entirely
      normal, as is the free-running period of the circadian pacemaker. The lark strain
      carries a single P-element insertion which, interestingly, has a dominant effect
      on the timing of eclosion, but is also associated with a recessive embryonic
      lethal phenotype. The analysis of excision-generated alleles suggests that the
      lark gene encodes an essential function. This function is apparently mediated by
      a transcription unit that is interrupted by the P-induced lark mutation. A
      combination of in situ hybridization analysis and reporter (beta-gal) staining
      indicates that this transcription unit expresses mRNAs throughout the embryonic
      central nervous system and in a defined subset of cells in the nervous system of
      pharate adults. RNAs are first detected at about embryonic stage 11, just prior
      to the stage at which lethality occurs in lark homozygotes. Based primarily on
      the observed mutant phenotypes, a function is proposed for the LARK product(s)
      that is consistent with the pleiotropic nature of lark mutations.

PMID- 8307325
TI  - Effects of multiple retrovirus insertions on quantitative traits of mice.
AB  - To assess the potential to generate quantitative genetic variation by insertional
      mutagenesis in a vertebrate, lines of mice in which many provirus vector inserts
      segregated at a low initial frequency on an inbred background (insert lines) were
      subjected to divergent artificial selection on body weight at 6 weeks and
      responses and heritability estimates compared to control lines lacking inserts.
      Heritability estimates were more than 1.5 times greater in the insert lines than
      in the controls, but because the phenotypic variance was substantially higher in
      the insert lines the genetic variance was about 3 times greater. Realized
      heritability estimates tended to be lower than heritabilities estimated by an
      animal model which utilizes information in covariances between all relatives in
      the data set. A surprisingly large response to selection occurred in the inbred
      control line. Insert lines were about 20% less fertile than controls. Division of
      the selection lines into inbred sublines in the later generations of the
      experiment revealed substantially greater variation among sublines of the insert
      lines than among the controls. Heritabilities were similar to typical estimates
      for the trait in outbred populations. In conclusion, there was clear evidence of
      extra variation deriving from inserts, which has yet to be attributed to
      individual genes.

PMID- 8307326
TI  - Molecular analysis of radiation-induced albino (c)-locus mutations that cause
      death at preimplantation stages of development.
AB  - Deletion mutations at the albino (c) locus have been useful for continuing the
      development of fine-structure physical and functional maps of the Fes-Hbb region
      of mouse chromosome 7. This report describes the molecular analysis of a number
      of radiation-induced c deletions that, when homozygous, cause death of the embryo
      during preimplantation stages. The distal extent of these deletions defines a
      locus, pid, (preimplantation development) genetically associated with this
      phenotype. The proximal breakpoints of eight of these deletions were mapped with
      respect to the Tyr (tyrosinase; albino) gene as well as to anonymous loci within
      the Fah-Tyr region that are defined by the Pmv-31 viral integration site and by
      chromosome-microdissection clones. Rearrangements corresponding to the proximal
      breakpoints of two of these deletions were detected by Southern blot analysis,
      and a size-altered restriction fragment carrying the breakpoint of one of them
      was cloned. A probe derived from this deletion fusion fragment defines a locus,
      D7Rn6, which maps within (or distal to) the pid region, and which discriminates
      among the distal extents of deletions eliciting the pid phenotype. Extension of
      physical maps from D7Rn6 should provide access both to the pid region and to loci
      mapping distal to pid that are defined by N-ethyl-N-nitrosourea-induced lethal
      mutations.

PMID- 8307327
TI  - Deletion mapping of four loci defined by N-ethyl-N-nitrosourea-induced
      postimplantation-lethal mutations within the pid-Hbb region of mouse chromosome
      7.
AB  - As part of a long-term effort to refine the physical and functional maps of the
      Fes-Hbb region of mouse chromosome 7, four loci [l(7)1Rn, l(7)2Rn, l(7)3Rn,
      l(7)4Rn] defined by N-ethyl-N-nitrosourea (ENU)-induced, prenatally lethal
      mutations were mapped by means of trans complementation crosses to mice carrying
      lethal deletions of the mouse chromosome-7 albino (c) locus. Each locus was
      assigned to a defined subregion of the deletion map at the distal end of the Fes
      Hbb interval. Of particular use for this mapping were preimplantation-lethal
      deletions having distal breakpoints localized between pid and Omp. Hemizygosity
      or homozygosity for each of the ENU-induced lethals was found to arrest
      development after uterine implantation; the specific time of postimplantation
      death varied, and depended on both the mutation itself and on whether it was
      hemizygous or homozygous. Based on their map positions outside of and distal to
      deletions that cause death at preimplantation stages, these ENU-induced mutations
      identify loci, necessary for postimplantation development, that could not have
      been discovered by phenotypic analyses of mice homozygous for any albino
      deletion. The mapping of these loci to specific genetic intervals defined by
      deletion breakpoints suggests a number of positional-cloning strategies for the
      molecular isolation of these genes. Phenotypic and genetic analyses of these
      mutations should provide useful information on the functional composition of the
      corresponding segment of the human genome (perhaps human 11q13.5).

PMID- 8307328
TI  - Evolution of multilocus genetic structure in Avena hirtula and Avena barbata.
AB  - Avena barbata, an autotetraploid grass, is much more widely adapted than Avena
      hirtula, its diploid ancestor. We have determined the 14-locus genotype of 754
      diploid and 4751 tetraploid plants from 10 and 50 Spanish sites, respectively.
      Allelic diversity is much greater in the tetraploid (52 alleles) than in the
      diploid (38 alleles): the extra alleles of the tetraploid were present in
      nonsegregating heteroallelic quadriplexes. Seven loci were monomorphic for the
      same allele (genotypically 11) in all populations of the diploid: five of these
      loci were also monomorphic for the same allele (genotypically 1111) in all
      populations of the tetraploid whereas two loci each formed a heteroallelic
      quadriplex (1122) that was monomorphic or predominant in the tetraploid. Seven of
      the 14 loci formed one or more highly successful homoallelic and/or heteroallelic
      quadriplexes in the tetraploid. We attribute much of the greater heterosis and
      wider adaptedness of the tetraploid to favorable within-locus interactions and
      interlocus (epistatic) interactions among alleles of the loci that form
      heteroallelic quadriplexes. It is difficult to account for the observed patterns
      in which genotypes are distributed ecogeographically except in terms of natural
      selection favoring particular alleles and genotypes in specific habitats. We
      conclude that natural selection was the predominant integrating force in shaping
      the specific genetic structure of different local populations as well as the
      adaptive landscape of both the diploid and tetraploid.

PMID- 8307329
TI  - Two maize genes are each targeted predominantly by distinct classes of Mu
      elements.
AB  - The Mutator transposable element system of maize has been used to isolate
      mutations at many different genes. Six different classes of Mu transposable
      elements have been identified. An important question is whether particular
      classes of Mu elements insert into different genes at equivalent frequencies. To
      begin to address this question, we used a small number of closely related Mutator
      plants to generate multiple independent mutations at two different genes. The
      overall mutation frequency was similar for the two genes. We then determined what
      types of Mu elements inserted into the genes. We found that each of the genes was
      preferentially targeted by a different class of Mu element, even when the two
      genes were mutated in the same plant. Possible explanations for these findings
      are discussed. These results have important implications for cloning Mu-tagged
      genes as other genes may also be resistant or susceptible to the insertion of
      particular classes of Mu elements.

PMID- 8307330
TI  - The role of the ameiotic1 gene in the initiation of meiosis and in subsequent
      meiotic events in maize.
AB  - Understanding the initiation of meiosis and the relationship of this event with
      other key cytogenetic processes are major goals in studying the genetic control
      of meiosis in higher plants. Our genetic and structural analysis of two mutant
      alleles of the ameiotic1 gene (am1 and am1-praI) suggest that this locus plays an
      essential role in the initiation of meiosis in maize. The product of the
      ameiotic1 gene affects an earlier stage in the meiotic sequence than any other
      known gene in maize and is important for the irreversible commitment of cells to
      meiosis and for crucial events marking the passage from premeiotic interphase
      into prophase I including chromosome synapsis. It appears that the period of
      ameiotic1 gene function in meiosis at a minimum covers the interval from some
      point during premeiotic interphase until the early zygotene stage of meiosis. To
      study the interaction of genes in the progression of meiosis, several double
      meiotic mutants were constructed. In these double mutants (i) the ameiotic1
      mutant allele was brought together with the meiotic mutation (afd1) responsible
      for the fixation of centromeres in meiosis; and with the mutant alleles of the
      three meiotic genes that control homologous chromosome segregation (dv1, ms43 and
      ms28), which impair microtubule organizing center organization, the orientation
      of the spindle fiber apparatus, and the depolymerization of spindle filaments
      after the first meiotic division, respectively; (ii) the afd1 mutation was
      combined with two mutations (dsy1 and as1) affecting homologous pairing; (iii)
      the ms43 mutation was combined with the as1, the ms28 and the dv1 mutations; and
      (iv) the ms28 mutation was combined with the dv1 mutation and the ms4
      (polymitotic1) mutations. An analysis of gene interaction in the double mutants
      led us to conclude that the ameiotic1 gene is epistatic over the afd1, the dv1,
      the ms43 and the ms28 genes but the significance of this relationship requires
      further analysis. The afd gene appears to function from premeiotic interphase
      throughout the first meiotic division, but it is likely that its function begins
      after the start of the ameiotic1 gene expression. The afd1 gene is epistatic over
      the two synaptic mutations dsy1 and as1 and also over the dv1 mutation. The new
      ameiotic*-485 and leptotene arrest*-487 mutations isolated from an active
      Robertson's Mutator stocks take part in the control of the initiation of meiosis.

PMID- 8307331
TI  - Application of a random walk model to geographic distributions of animal
      mitochondrial DNA variation.
AB  - In rapidly evolving molecules, such as animal mitochondrial DNA, mutations that
      delineate specific lineages may not be dispersed at sufficient rates to attain an
      equilibrium between genetic drift and gene flow. Here we predict conditions that
      lead to nonequilibrium geographic distributions of mtDNA lineages, test the
      robustness of these predictions and examine mtDNA data sets for consistency with
      our model. Under a simple isolation by distance model, the variance of an mtDNA
      lineage's geographic distribution is expected be proportional to its age.
      Simulation results indicated that this relationship is fairly robust. Analysis of
      mtDNA data from natural populations revealed three qualitative distributional
      patterns: (1) significant departure of lineage structure from equilibrium
      geographic distributions, a pattern exhibited in three rodent species with
      limited dispersal; (2) nonsignificant departure from equilibrium expectations,
      exhibited by two avian and two marine fish species with potentials for relatively
      long-distance dispersal; and (3) a progression from nonequilibrium distributions
      for younger lineages to equilibrium distributions for older lineages, a condition
      displayed by one surveyed avian species. These results demonstrate the advantages
      of considering mutation and genealogy in the interpretation of mtDNA geographic
      variation.

PMID- 8307332
TI  - Effective sizes for subdivided populations.
AB  - Many derivations of effective population sizes have been suggested in the
      literature; however, few account for the breeding structure and none can readily
      be expanded to subdivided populations. Breeding structures influence gene
      correlations through their effects on the number of breeding individuals of each
      sex, the mean number of progeny per female, and the variance in the number of
      progeny produced by males and females. Additionally, hierarchical structuring in
      a population is determined by the number of breeding groups and the migration
      rates of males and females among such groups. This study derives analytical
      solutions for effective sizes that can be applied to subdivided populations.
      Parameters that encapsulate breeding structure and subdivision are utilized to
      derive the traditional inbreeding and variance effective sizes. Also, it is shown
      that effective sizes can be determined for any hierarchical level of population
      structure for which gene correlations can accrue. Derivations of effective sizes
      for the accumulation of gene correlations within breeding groups (coancestral
      effective size) and among breeding groups (intergroup effective size) are given.
      The results converge to traditional, single population measures when similar
      assumptions are applied. In particular, inbreeding and intergroup effective sizes
      are shown to be special cases of the coancestral effective size, and intergroup
      and variance effective sizes will be equal if the population census remains
      constant. Instantaneous solutions for effective sizes, at any time after gene
      correlation begins to accrue, are given in terms of traditional F statistics or
      transition equations. All effective sizes are shown to converge upon a common
      asymptotic value when breeding tactics and migration rates are constant. The
      asymptotic effective size can be expressed in terms of the fixation indices and
      the number of breeding groups; however, the rate of approach to the asymptote is
      dependent upon dispersal rates. For accurate assessment of effective sizes,
      initial, instantaneous or asymptotic, the expressions must be applied at the
      lowest levels at which migration among breeding groups is nonrandom. Thus, the
      expressions may be applicable to lineages within socially structured populations,
      fragmented populations (if random exchange of genes prevails within each
      population), or combinations of intra- and interpopulation discontinuities of
      gene flow. Failure to recognize internal structures of populations may lead to
      considerable overestimates of inbreeding effective size, while usually
      underestimating variance effective size.

PMID- 8307333
TI  - A notable triumvirate of maize geneticists.

PMID- 8307334
TI  - The pheromone receptors inhibit the pheromone response pathway in Saccharomyces
      cerevisiae by a process that is independent of their associated G alpha protein.
AB  - Dominant mutations at the DAF2 locus confer resistance to the cell-cycle arrest
      that normally occurs in MATa cells exposed to alpha-factor. One of these alleles,
      DAF2-2, has also been shown to suppress the constitutive signaling phenotype of
      null alleles of the gene encoding the alpha subunit of the G protein involved in
      pheromone signaling. These observations indicate that DAF2-2 inhibits
      transmission of the pheromone response signal. The DAF2-2 mutation has two
      effects on the expression of a pheromone inducible gene, FUS1. In DAF2-2 cells,
      FUS1 RNA is present at an increased basal level but is no longer fully inducible
      by pheromone. Cloning of DAF2-2 revealed that it is an allele of STE3, the gene
      encoding the a-factor receptor. STE3 is normally an alpha-specific gene, but is
      inappropriately expressed in a cells carrying a STE3DAF2-2 allele. The two
      effects of STE3DAF2-2 alleles on the pheromone response pathway are the result of
      different functions of the receptor. The increased basal level of FUS1 RNA is
      probably due to stimulation of the pathway by an autocrine mechanism, because it
      required at least one of the genes encoding a-factor. Suppression of a null
      allele of the G alpha subunit gene, the phenotype associated with the inhibitory
      function of STE3, was independent of a-factor. This suppression was also observed
      when the wild-type STE3 gene was expressed in a cells under the control of an
      inducible promoter. Inappropriate expression of STE2 in alpha cells was able to
      suppress a point mutation, but not a null allele, of the G alpha subunit gene.
      The ability of the pheromone receptors to block the pheromone response signal in
      the absence of the G alpha subunit indicates that these receptors interact with
      another component of the signal transduction pathway.

PMID- 8307335
TI  - Deletion of a single-copy tRNA affects microtubule function in Saccharomyces
      cerevisiae.
AB  - rts1-1 was identified as an extragenic suppressor of tub2-104, a cold-sensitive
      allele of the sole gene encoding beta-tubulin in the yeast, Saccharomyces
      cerevisiae. In addition, rts1-1 cells are heat sensitive and resistant to the
      microtubule-destabilizing drug, benomyl. The rts1-1 mutation is a deletion of
      approximately 5 kb of genomic DNA on chromosome X that includes one open reading
      frame and three tRNA genes. Dissection of this region shows that heat sensitivity
      is due to deletion of the open reading frame (HIT1). Suppression and benomyl
      resistance are caused by deletion of the gene encoding a tRNA(Arg)AGG (HSX1).
      Northern analysis of rts1-1 cells indicates that HSX1 is the only gene encoding
      this tRNA. Deletion of HSX1 does not suppress the tub2-104 mutation by misreading
      at the AGG codons in TUB2. It also does not suppress by interfering with the
      protein arginylation that targets certain proteins for degradation. These results
      leave open the prospect that this tRNA(Arg)AGG plays a novel role in the cell.

PMID- 8307337
TI  - Ends-in vs. ends-out recombination in yeast.
AB  - Integration of linearized plasmids into yeast chromosomes has been used as a
      model system for the study of recombination initiated by double-strand breaks.
      The linearized plasmid DNA recombines efficiently into sequences homologous to
      the ends of the DNA. This efficient recombination occurs both for the
      configuration in which the break is in a contiguous region of homology (herein
      called the ends-in configuration) and for "omega" insertions in which plasmid
      sequences interrupt a linear region of homology (herein called the ends-out
      configuration). The requirements for integration of these two configurations are
      expected to be different. We compared these two processes in a yeast strain
      containing an ends-in target and an ends-out target for the same cut plasmid.
      Recovery of ends-in events exceeds ends-out events by two- to threefold. Possible
      causes for the origin of this small bias are discussed. The lack of an extreme
      difference in frequency implies that cooperativity between the two ends does not
      contribute to the efficiency with which cut circular plasmids are integrated.
      This may also be true for the repair of chromosomal double-strand breaks.

PMID- 8307336
TI  - Spo12 is a limiting factor that interacts with the cell cycle protein kinases
      Dbf2 and Dbf20, which are involved in mitotic chromatid disjunction.
AB  - The DBF2 and DBF20 genes of the budding yeast Saccharomyces cerevisiae encode a
      pair of structurally similar protein kinases. Although yeast with either gene
      deleted is viable, deletion of both genes is lethal. Thus, the Dbf2 and Dbf20
      proteins are functional alternatives for an essential activity. In contrast to
      deletions, four different mutant alleles of DBF2 are lethal. Thus, the presence
      of a nonfunctional Dbf2 protein, rather than the lack of function per se, is
      inhibitory. Here we present genetic evidence that nonfunctional mutant Dbf2
      protein blocks the function of Dbf20 protein by sequestering a common interacting
      protein encoded by SPO12. Even a single extra copy of SPO12 is sufficient to
      suppress the dbf2 defect. Since SPO12 appears to encode a limiting factor, it may
      be a rate limiting cofactor that is involved in the regulation of the Dbf2 and
      Dbf20 protein kinases. A corollary to the finding that one extra copy of SPO12
      can suppress dbf2, is that the acquisition of an extra chromosome VIII, which
      carries the SPO12 locus, will also suppress dbf2. Indeed, physical analysis of
      chromosome copy number in dbf2 revertants able to grow at 37 degrees showed that
      the frequency of chromosome VIII acquisition increased when cells were incubated
      at the restrictive temperature, and reached a frequency of more than 100-fold the
      amount in wild-type yeast. This suggested that the dbf2 mutation was not only
      suppressed by an extra copy of chromosome VIII but also that the dbf2 mutation
      actually caused aberrant chromosomal segregation. Conventional assays for
      chromosome loss confirmed this proposal.

PMID- 8307338
TI  - Generation of temperature-sensitive cbp1 strains of Saccharomyces cerevisiae by
      PCR mutagenesis and in vivo recombination: characteristics of the mutant strains
      imply that CBP1 is involved in stabilization and processing of cytochrome b pre
      mRNA.
AB  - Mitochondrial biogenesis is dependent on both nuclearly and mitochondrially
      encoded proteins. Study of the nuclearly encoded mitochondrial gene products and
      their effect on mitochondrial genome expression is essential to understanding
      mitochondrial function. Mutations in the nuclear gene CBP1 of Saccharomyces
      cerevisiae result in degradation of mitochondrially encoded cytochrome b (cob)
      RNA; thus, the cells are unable to respire. Putative roles for the CBP1 protein
      include processing of precursor RNA to yield the mature 5' end of cob mRNA and/or
      physical protection of the mRNA from degradation by nucleases. To examine the
      activity of CBP1, we generated temperature-sensitive cbp1 mutant strains by
      polymerase chain reaction (PCR) mutagenesis and in vivo recombination. These
      temperature-sensitive cbp1 strains lack cob mRNA only at the nonpermissive
      temperature. Quantitative primer extension analyses of RNA from these strains and
      from a cbp1 deletion strain demonstrated that CBP1 is required for the stability
      of precursor RNAs in addition to production of the stable mature mRNA. Thus, CBP1
      is not involved solely in the protection of mature cob mRNA from nucleases.
      Moreover, we found that mature mRNAs are undetectable while precursor RNAs are
      reduced only slightly at the nonpermissive temperature. Collectively, these data
      lead us to favor a hypothesis whereby CBP1 protects cob precursor RNAs and
      promotes the processing event that generates the mature 5' end of the mRNA.

PMID- 8307339
TI  - Plasmid suppressors active in the sexual cycle of Neurospora intermedia.
AB  - We have discovered that, in certain crosses of natural isolates of Neurospora
      intermedia, linear and circular mitochondrial plasmids of the maternal parent are
      not transmitted to the progeny. This contrasts with the maternal transmission of
      organellar genetic elements generally observed in crosses between laboratory
      strains and between other natural isolates. Formally, failure of plasmid
      transmission is a type of plasmid suppression. The present cases represent the
      first report of plasmid suppressors in natural populations of fungi. Strains used
      as female parents can transmit or not transmit plasmids depending on the strain
      used as male parent. Males that act to suppress in one cross fail to suppress in
      others. Therefore, the suppression of plasmids depends on a strain-specific
      interaction and is not determined exclusively by the males. Since suppression is
      a specific interaction we inferred that it must be genetically based and tested
      this hypothesis by seeking segregation of suppressed and nonsuppressed phenotypes
      in octads. Segregation of the original full suppression of all plasmids was
      indeed observed in each of the three sets of testcrosses examined. The
      interaction type of suppression must be initiated in ascogenous tissue during the
      sexual cycle. It is a nonautonomous type of suppression, affecting all descendent
      cells. In any one case of suppression, either one, several, or all plasmids can
      be lost. Both linear and circular plasmids can be eliminated by the same
      suppressor genotype. In addition, several strains were found to contain
      suppressors that act after ascospore delineation. This autonomous type of
      suppression has been observed previously in laboratory strains, but not in
      natural isolates. All the cases of plasmid suppression identified in this study
      involved a range of apparently neutral circular and linear plasmids. Using one
      senescent Kalilo strain of N. intermedia, we did not detect any case of
      suppression of the senescence-determining linear plasmid kalDNA.

PMID- 8307340
TI  - The array of psychiatric services in general hospitals.
AB  - This paper examines the frequency with which general hospitals with inpatient
      psychiatric units provide psychiatric emergency, outpatient, and partial hospital
      care. An analysis is presented of data from the 1988 American Hospital
      Association Annual Survey of Hospitals focusing on the number and proportion of
      general hospitals with psychiatric units that offer psychiatric emergency,
      outpatient, and partial hospital services. The vast majority (82.6%) of general
      hospitals with psychiatric units provided psychiatric emergency room services,
      approximately half (50.3%) provided psychiatric outpatient services, and slightly
      over a third (37.9%) offered partial hospitalization services. General hospitals
      with psychiatric units were more likely to provide outpatient psychiatric
      services if they were under private nonprofit or nonfederal governmental control
      than if they were under private for-profit control. General hospitals with
      inpatient substance abuse treatment services were more likely to provide
      complementary outpatient services than were general hospitals with inpatient
      psychiatric services (70.8% vs 50.3%). The results indicate that at half of the
      hospitals with psychiatric units, discharge planning necessarily involves
      referring patients outside of the hospital for continuing care.

PMID- 8307341
TI  - The impact of a meditation-based stress reduction program on fibromyalgia.
AB  - Fibromyalgia is a chronic illness characterized by widespread pain, fatigue,
      sleep disturbance, and resistance to treatment. The purpose of this study was to
      evaluate the effectiveness of a meditation-based stress reduction program on
      fibromyalgia. Seventy-seven patients meeting the 1990 criteria of the American
      College of Rheumatology for fibromyalgia took part in a 10-week group outpatient
      program. Therapists followed a carefully defined treatment approach and met
      weekly to further promote uniformity. Patients were evaluated before and after
      the program. Initial evaluation included a psychiatric structured clinical
      interview (SCID). Outcome measures included visual analog scales to measure
      global well-being, pain, sleep, fatigue, and feeling refreshed in the morning.
      Patients also completed a medical symptom checklist, SCL-90-R, Coping Strategies
      Questionnaire, Fibromyalgia Impact Questionnaire, and the Fibromyalgia Attitude
      Index. Although the mean scores of all the patients completing the program showed
      improvement, 51% showed moderate to marked improvement and only they were counted
      as "responders." These preliminary findings suggest that a meditation-based
      stress reduction program is effective for patients with fibromyalgia.

PMID- 8307342
TI  - A model integrating mental health and primary care services for families with
      HIV.
AB  - The need to integrate mental health and primary care service delivery for
      individuals and families living with human immunodeficiency virus (HIV) and
      acquired immune deficiency syndrome (AIDS) has been well documented.
      Accessibility, flexibility, and cultural specificity are qualities necessary, but
      generally lacking, in existing models of integrated care. In this paper, NOAH (No
      One Alone with HIV), an innovative, hospital-based program of family-focused HIV
      mental health services, will be described. NOAH is designed to meet the needs of
      primary care providers, allied professionals/paraprofessionals, and the diversity
      of inner-city patients they serve. Central to the model are population-specific
      "family health facilitators," who collaborate with providers by offering mental
      health interventions at one or more levels along a continuum of service
      intensity. Whenever possible, primary care team members are empowered to manage
      mental health problems directly. When more intensive services are required,
      responsibility for direct intervention transfers to the family health
      facilitator. With the locus of inner-city HIV primary care shifting from
      hospitals to neighborhood health centers, this hospital-based program has been
      extended into the community to support the early integration of mental health and
      primary care services at the community level.

PMID- 8307343
TI  - Inpatient suicide in a general hospital psychiatric unit. A consequence of
      inadequate resources?
AB  - The incidence of suicide and high lethality attempted suicide in the 20-bed
      inpatient psychiatric unit of a general hospital was reviewed over a 10-year
      period. Although locating accurate records was difficult, a trend suggestive of
      increasing incidence was identified. We noted that this observation corresponded
      with an increase in the number of patients being treated by staff on the ward,
      reduced length of stay, and an increase in the proportion of severely disordered
      patients. Although the ward was accepting a greater number of patients, the
      available facilities (both physical resources and personnel) were not changed
      until the early results of this study were known (late 1991). We suggest that the
      clinical demands placed upon a psychiatric facility may affect the incidence of
      suicide and attempted suicide. This has particular significance in the general
      hospital setting where resources may be limited by competing requirements from
      other units and the current trend to close large mental hospitals places more
      demand upon them.

PMID- 8307344
TI  - Crisis hospitalization on a psychiatric emergency service.
AB  - The availability of short-stay beds for brief admissions to a Psychiatric
      Emergency Service (PES) is a model that meets a variety of patient and system
      needs, allowing time to develop alternatives to hospitalization or gain
      diagnostic clarity, serving a respite function, providing a hospital setting that
      does not gratify dependency needs, and relieving inpatient census pressures. An
      eight-bed service for brief inpatient stays of up to 3 days was developed on a
      PES which serves a large nine-country catchment area in northeastern New York
      State. Admissions to this unit would otherwise have gone to a medical school
      teaching hospital psychiatric unit or a state psychiatric center. Fifty-one
      consecutive admissions were studied. The majority of patients were dischargeable
      in the short time frame and did not require transfer for longer-term care. The
      patients as a group showed improvement in psychiatric symptomatology and rated
      high satisfaction with the program. Most patients were diagnosed with
      schizophrenia or personality disorder (PD). Suicidality and substance abuse were
      frequent. The PD patients had a strong association with suicidality and some
      association with substance abuse, whereas the schizophrenics had more psychiatric
      symptomatology. PD patients were more likely to be discharged, leading us to
      propose a rationale for why this group may be uniquely suited to this approach.
      The study was replicated after a year on another sample of 51 consecutive
      admissions, confirming the earlier results and providing a 1-year follow-up on
      the program.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307345
TI  - Dimensions and predictors of change during brief psychiatric hospitalization.
AB  - The effects of brief psychiatric hospitalization on patient functioning remain
      controversial and poorly defined. In this study, 217 subjects were evaluated for
      the changes they experienced during a brief admission (average length of stay
      23.0 +/- 16.2 days). Significant improvements occurred in symptoms, global
      functioning, self-esteem, perceptions of others, and ego functioning. Better
      multidimensional outcome correlated with symptomatic improvement and preadmission
      functioning. No effects were found for age, gender, Axis I diagnosis, presence of
      an Axis II or Axis III disorder, prior hospitalization, severity of symptoms,
      length of stay, or payor group. During brief hospitalization, patients appear to
      improve in several areas of psychosocial functioning.

PMID- 8307346
TI  - Is there a relationship between reflex sympathetic dystrophy and helplessness?
      Case reports and a hypothesis.
AB  - Five case reports that illustrate the possible contribution of psychological
      factors in the etiopathogenesis of reflex sympathetic dystrophy (RSD) are
      presented. All five patients at the time of physical trauma were confronted with
      a significant loss that either accidentally coincided with the trauma, or was
      related to the experience of the trauma itself. The patients' reaction to the
      loss was invariably characterized by helplessness. A biopsychosocial hypothesis
      which considers the possible role of psychophysiological and behavioral aspects
      of helplessness in the precipitation, maintenance, and/or enhancement of RSD is
      outlined.

PMID- 8307347
TI  - Alexithymia in psychiatric consultation-liaison patients.
AB  - Alexithymic characteristics were assessed by the Toronto Alexithymia Scale (TAS),
      a self-report measure of alexithymia, in 230 consecutive outpatients referred to
      a psychiatric consultation-liaison service. The prevalence of alexithymia was
      37.8% (50.5% in men and 28.2% in women). Alexithymia was significantly associated
      with the following variables: male gender, low socioeconomic status, the presence
      of psychiatric disorder, especially depression, with old age and with a high
      level of psychological distress. No significant association between alexithymia
      and the presence of somatic illness was found.

PMID- 8307348
TI  - Attitudes of pediatricians toward psychiatric consultations.
AB  - This study attempts to evaluate the psychiatric consultation services in both a
      university and a non-university children's hospital by requesting opinions from
      121 pediatricians. A 26-item questionnaire asked pediatricians to comment on the
      percentage of their patients with psychological problems and their level of ease
      in dealing with them, problems making psychiatric referrals, and their level of
      satisfaction with psychiatric consultations and other consultation activities.
      There were no significant differences between the attitudes of physicians from
      the two hospitals. Overall, the level of satisfaction was very low, indicating a
      need for a better working relationship between pediatric and child psychiatry
      units. There appears to be a high level of readiness on the pediatricians' side
      to enhance the relationship between the two clinical disciplines.

PMID- 8307349
TI  - ECT emergence agitation and methohexital-succinylcholine interaction. Case
      report.
AB  - Two separate methods of preventing post-ECT emergence agitation are increasing
      the succinylcholine dose to about 1.1 mg/kg and adding a methohexital bolus of
      about 0.67 mg/kg immediately at seizure end. These methods can work separately
      and additively without any expectation of diminishing treatment efficacy. A
      relevant case is described.

PMID- 8307350
TI  - [The evolutionarily conserved gene Nc70F, expressed in nerve tissue of Drosophila
      melanogaster, encodes a protein homologous to the mouse delta transcription
      factor].
AB  - A cDNA copy of the Nc70F gene which is specifically expressed in Drosophila
      neural tissue was cloned and characterized. The gene has an open reading frame
      for the protein of 384 amino acids. The protein contains dimerization, DNA
      binding, activation and repression domains which are common for the eucaryotic
      transcription factors. However, the domain organization of the Nc70F protein has
      some peculiarities. The primary structure of the Nc70F product and other
      transcription factors were compared. High level of homology of Nc70F protein with
      the mouse delta transcription factor was found. The in situ hybridization on
      tissue section showed that the Nc70F gene expression is restricted to the central
      nerve system at all stages of Drosophila ontogenesis. By using Drosophila genomic
      and cDNA clones of Nc70F genes as probes, homologous transcripts were identified
      in the human poly(A) +RNA. The evolutionary conservative portion of this gene was
      localized in the 5-exons.

PMID- 8307351
TI  - [Family analysis of human "fingerprints" obtained using a phage M13 DNA probe].
AB  - The human "fingerprints" detected by the phage M13 DNA probe from 40 simple
      families with some presumably genetic malformations were observed. When only one
      parent had a specific band, the mean segregation frequency of all the
      electrophoretic bands detected was equal to 0.485, which confirmed the hypothesis
      about the Mendelian inheritance and high level of heterozygosity of hypervariable
      loci. The mean new measure of similarity between the parents calculated by Li
      C.C. was 0.54 (this measure within only fathers and only mothers was equal to the
      mean population level of similarity 0.41).

PMID- 8307352
TI  - [Genetic distances between various ethnic populations calculated on the basis of
      polymorphism of DNA detected by the hypervariable phage M13 DNA probe].
AB  - The frequencies of different electrophoretic bands in DNA "fingerprint" detected
      by the phage M13 DNA probe in six Russian populations from the Kirov district and
      Krasnodar, one from Chuvashia and one from Tuva were compared with each other and
      pseudo-genetic distances by Nei were calculated. The results corresponded well
      with a presumable extent of similarity between the populations observed.

PMID- 8307353
TI  - [Mutational analysis of the genes encoding the photosystem II proteins in
      Cyanobacterium synechocystis sp. 6803].
AB  - Chlorophyll--binding protein CP43 and cytochrome b559, encoded by psbC and psbE/F
      genes, are the components of photosystem II (PS II). Three psbC- and four psbE/F-
      mutants were isolated from the collection of PS II-deficient mutants of the
      cyanobacterium Synechocystis sp. 6803. Restoration of photosynthetic activity was
      achieved by transformation of psbE/F- mutants with cloned psbE/F gene cluster
      from wild type cells and each of psbC- mutants--with specific part of wild type
      psbC gene. DNA fragments carrying the mutations were isolated from mutant cells
      and sequenced. The mutations which affect PS II activity were identified in psbC
      gene as "frameshift" mutation, stop-codon formation, or as deletion of three
      nucleotides resulting in loss of one of three Phe residues in position 422-424 of
      CP43. Sequence of mutant psbE/F genes revealed single mutations resulting in
      deletion of Phe-36 or substitution of Pro-63 for Leu in alpha-subunit and Val-29
      for Phe in beta-subunit of cytochrome b559.

PMID- 8307354
TI  - [Effect of structural features of nitro-derivatives of fluorenone and biphenyl on
      frameshift mutagenesis in tester strains of Salmonella typhimurium].
AB  - Comparative mutagenic activity of 7 derivatives of biphenyl and fluorenone, 4,4'
      dinitrobiphenyl-2,2'-dicarboxylic acid; 4,4',6,6'-tetranitrobiphenyl-2,2'
      dicarboxylamide; 2-nitrofluorenone-5-carboxylic acid; 2,7-dinitrofluorenone-5
      carboxylic acid; 2,7-dinitrofluorenone-5-carboxylamide; 2-nitrofluorenone-5,7
      dicarboxylic acid; 2,4-dinitrofluorenone-5,7-dicarboxylic acid was studied. The
      highest activity was demonstrated for 2,7-DNF-5-KA and 2,7-DNF-5,7-DK which
      induced frameshift mutations in the tester strains Salmonella typhimurium TA1537,
      TA97, TA1538, TA98. High mutagenicity of these compounds is correlated with the
      position of nitro-groups and the effects of carboxylic and carboxyamide groups.

PMID- 8307355
TI  - [Variation of behavioral traits in natural Drosophila melanogaster populations
      from Eurasia].
AB  - Two behavior traits--phototactic response and locomotor activity--were studied in
      13 populations of Drosophila melanogaster with countercurrent distribution
      technique. These traits were characterized by three parameters: average
      phototactic (locomotor) activity, normalized variance of activity and proportion
      of inactive flies. Males had bigger average phototactic activity and average
      locomotor activity, but less proportion of inactive flies than females. For
      phototaxis, no correlation was found between all estimated parameters and
      geographic localization of populations. For locomotor activity, females exhibited
      clinal variation in proportion of inactive flies.

PMID- 8307356
TI  - [Frequent occurrence of BoLA w16 in cows susceptible to mastitis].
AB  - The association between BoLA class I antigens and mastitis was studied in Boheman
      Pied breed and its crosses. The mastitis status was followed during two years
      according to three diagnostic criteria: California Mastitis Test, bacteriological
      findings and the altered taste of milk. The antigen w16 was found to be
      significantly associated with susceptibility to mastitis in all diagnostic tests.
      On the other hand there were some indications that the wll animals were rather
      resistant to mastitis.

PMID- 8307357
TI  - [Heterozygosity and fertility in the Northern Selkup tribe].
AB  - The relationship between heterozygosity for 11 polymorphic loci and fertility of
      women having passed the menopause was studied in North-Siberian tribe North
      Selkup. Women with low level of heterozygosity were characterized by the highest
      values of variance of the number of livebirths and the index of early
      reproductive loss.

PMID- 8307358
TI  - [Variability of anthropometric traits in newborn offspring of Russian-Buryat
      unions].
AB  - The variation of 9 anthropometric traits of Buryat, Russian and (Russian x
      Buryat) F1 hybrid newborns was compared. Data show that hybrid newborns are
      markedly different either from Buryat or Russian newborns. These differences are
      associated with significant increase of correlation between 7 anthropometric
      traits in hybrid newborns. It is suggested that alteration of gene interaction in
      hybrids is the main reason of observed differences between them and Russian and
      Buryat newborns.

PMID- 8307359
TI  - [Various biochemical parameters in serum of pregnant women carrying fetuses with
      various congenital defects of development].
AB  - The number of changes in some maternal serum biochemical parameters for some
      congenital malformations are presented. In all pregnancies we observed low levels
      of LAT, AST, CPK, HBD, AP and high levels of GGTP, THY, amylase. These data
      demonstrate total depression in metabolism of women with an affected fetus. The
      biological basis of altered levels of enzymes in pregnancies with affected fetus
      is unclear.

PMID- 8307360
TI  - [Frequency distribution of HLA phenotypes, haplotypes and alleles in ethnic
      groups of Taimyr and Chukotka].
AB  - HLA typing data of two little populations living in Tajmyr peninsula (Dolgans and
      Nganasans) and Chukotka peninsula (Chukchas and Chuvantses) were presented. Our
      data were compared with the International standard distribution of class I HLA
      antigens in orients and its distribution in orients who live in the Asian part of
      Russia. Indexes of genetic distribution and genetic likeness were calculated.

PMID- 8307361
TI  - [The association of genetic and functional variability of alpha 1-antitrypsin in
      asbestosis].
AB  - The polymorphism and serum levels of alpha 1-antitrypsin (AT) were studied in
      asbestosis patients, the control and the workers exposed to mineral flax longer
      or less than ten years. M1S, M3S, M1Z and M2M2 phenotypes had low concentration
      of this protein. In the course of contact with mineral flax decrease in alpha 1
      AT concentration was found. The phenotypes with low protein levels were very rare
      among workers contacting with asbestos for a long time, and one of them--M1S was
      more often encountered in asbestosis patients. The standard deviation from the
      alpha 1-AT concentration was significantly higher in asbestosis patients.

PMID- 8307362
TI  - [Automated genetic register and computer support for the physician's diagnostic
      decisions].
AB  - Computer-based genetical register "GENREG" allows to carry out a prophylactic
      medical examination for families with children, having hereditary diseases,
      multifactorial pathology and congenital developmental defects of various nature,
      and also epidemiological examination. Automated consultative system for pre
      laboratory diagnosis of genetically determined diseases after the phenotypical
      manifestations "DIAGEN" allows to identify up to 1200 nosologic units; diagnostic
      value (or weight) of the signs according to physician's evaluation is taken into
      consideration. The system sorts out a narrow differential-and-diagnostic row and
      information about specific laboratory and functional changes for every selected
      diagnosis. Efficiency of the system is over 94% (after the next laboratory
      findings). The results of computer diagnosis and final physician's diagnosis, and
      also questionnaire of a child are stored in archives (files) of the "DIAGEN"
      system. Both of the systems are realized on PC/AT IBM-compatible computer.

PMID- 8307363
TI  - [Planning of samples for linkage analysis. Incomplete penetrance].
AB  - Dependence of the minimal size of a pedigree sample providing the given quality
      of a linkage decision on the genotype penetrance of the localized gene is
      considered. The two ways of the sample informativity increase are discussed and
      their effects are estimated. These ways are: the adequate choice of a marker gene
      and certain complication of a pedigree structure. It is shown for the latter that
      the effect can be achieved only for certain phenotypic characteristics of the
      additional pedigree members.

PMID- 8307364
TI  - [Frequency of various mini- and micro-satellite sequences in DNA of human
      chromosome 13].
AB  - The frequency of specific mini- and micro-satellites known also as short tandem
      repeated sequences (STR) in the human 13 chromosome was estimated by
      hybridization of STR core oligonucleotides to recombinant cosmid clones
      transferred to a grid from a human 13 chromosome specific cosmid library ICRF
      Lawrist 4 C108 (DN L4/HS 13). Oligonucleotides: M13 and Jeffreys minisatellite
      core sequences and micro-satellite core sequences (TCC)5, (CAC)5, and (GACA)4
      were [gamma-32P] end labeled and hybridized to membrane filters carrying good
      ordered cosmid clones. It was shown that great number of all these mini- and
      micro-satellite copies (besides of Jeffreys minisatellite) are spread
      independently along the 13th chromosome. It was also estimated that two or more
      (GACA)n blocks present in the same cosmid (i.e. on the stretch of 40-50 kb)
      forming similar groups of clustered micro-satellites. The interesting peculiarity
      has been recorded that some (GACA)n+ cosmids are also hybridizable to
      conservative 28SrDNA 3'-fragment that indicates that (GACA)n localization in the
      nucleoli area. As the result of it we began the creation of a new highly
      polymorphic markers collections for these chromosome.

PMID- 8307365
TI  - [Analysis of the selection process in breeding of caging populations of Arctic
      fox (Alopex lagopus L.)].
AB  - The purpose of this research is analysis of supporting heterozygosity mechanisms
      in caging population of Polar fox (Alopex lagopus L.). The polymorphism of the
      gene, which code the blood serum protein-transferrin, was used as a genetic
      marker. The level of the heterozygosity was studied in the reproductive and young
      parts of population. As it turned out, the reproductive part is separated on some
      subpopulations, moreover, inbreeding lead to the decrease of heterozygosity level
      in this part of population. On the other hand, selection which is to be held by a
      number of quantitative and qualitative signs in reproductive part of population
      promote to increase the number of heterozygous animals.

PMID- 8307367
TI  - [Complex instability in the system of hobo and stalker mobile element interaction
      in Drosophila melanogaster].
AB  - A number of mutations in different Drosophila loci resulted from the relationship
      between hobo and stalker mobile elements. In this investigation an insertion from
      the parential white mutation-waG-was cloned. And the Doc element, that is the
      reason of the mutation, is not moving in the observed instability system. But
      transpositions of the copia-like elements (e.g. mdg1, 2, 3 and copia) were shown
      in this system. A cases of chromosomal rearrangements and abnormal recombination
      in compound with transpositions of different mobile elements were found. Thus,
      the system of instability could be explained in terms of universal mechanism
      which involved both transpositions and recombinations phenomena.

PMID- 8307366
TI  - [Genetic regulation of limb development in vertebrates].
AB  - The data are surveyed concerning formation of limb buds in Vertebrate,
      development of morphogenetic fields in limb buds, their organization based on the
      simple gradient model and the model of polar coordinates. Formation of the
      morphogenetic fields of strictly located events, such as chondrogenesis and
      prescheduled cell death, based on the positional information is discussed. All
      the stages of limb formation in Vertebrate are under genetic control, the
      products of some genes behaving as extracellular factors (morphogens) and those
      of other as cell receptors or transcriptional factors inducing activity of
      specific gene sets. Highly important at that are regulatory homeobox genes.

PMID- 8307368
TI  - [Sequences resembling fragments of mitochondrial DNA in the human genome:
      features of evolution].
AB  - Mitochondrial-like sequences and their homologues from primate mitochondria are
      investigated to define direction and rate of evolution, time of integration into
      nuclear genome. The analysis showed that mito-like sequences differ from
      mitochondrial homologues by high level of symmetria of two chains of DNA. Besides
      that, difference between mito-like and Homo sapiens sequences in their GC
      contents is found. Apparently there is GC-pressure of nuclear genome region,
      being the place of integration of mito-like sequence, that brings about
      equalization of GC-contents in nuclear region and mito-like sequences. Properties
      of descent mitochondrial sequence play important role in the difference of mito
      like and Homo sapiens sequences also.

PMID- 8307369
TI  - [The use of Miniphage D3112 deltaHcts as an integrative vectorin Pseudomonas
      aeruginosa cells].
AB  - Catechol 2,3-dioxygenase gene (xylE) was cloned into the Pseudomonas aeruginosa
      miniphage D3112 delta Hcts. Miniphage provides an effective transduction of gene
      xylE and its transposition into different replicons. It can be used as an
      integrative vector in the P. aeruginosa cells. Besides, gene xylE is rather
      convenient genetic marker for identification of miniphage both in Excherichia
      coli and Pseudomonas species.

PMID- 8307370
TI  - [Establishment of linkage and the order of the genes GALA, G6PD, HPRT and PGK on
      the X-chromosome in two species of voles of the genus Microtus].
AB  - Localization of genes GALA, G6PD, HPRT and PGK on X-chromosome of Microtus
      subarvalis has been proved. Using the radiation hybrid mapping technique of Goss
      and Harris, the order of these genes for two species M. subarvalis and M.
      Kirgisorum was established. Statistical methods (program package RHMAP) result in
      the only gene order PKG--HPRT--G6PD--GALA for M. subarvalis. The same order was
      found to be the most probable for M. kirgisorum. Relative distances between these
      genes in two species appeared to be practically equal. A conservatism of a linear
      order of the X-linked genes in various mammalian taxons is discussed.

PMID- 8307371
TI  - [Possible mechanisms of the emergence of chromosome rearrangements. VI. Mitotic
      delay as a protective mechanism. Origin of spontaneous chromosome breaks].
AB  - It was proved by the investigation of the bone marrow cells and the culture of
      embryonic fibroblasts of mice, that experimental induction of chromosome breaks
      having such a distinctive feature as disposition of acentrics outside the
      equatorial plate at metaphase, results in reduction of the mitotic index and the
      radiation induced structural mutations frequency. Such disposition of acentrics-
      outside the equatorial plate--is typical for spontaneous chromosome breaks. It
      was suggested, that the process resulting in spontaneous chromosome breaks is a
      component of the protective mechanism, which is put into effect through the
      mitotic delay.

PMID- 8307372
TI  - [Genetic aspects of microphylogeny of nine breeds of rabbits raised in Russia].
AB  - Distribution of the frequencies of alleles and genotypes of albumin, post
      albumin, transferrin, post-transferrin and haemoglobin in 9 breeds of rabbits in
      Russia was analyzed. Genetic distances between these breeds were defined and the
      dendrograms of their phylogeny composed. The smallest distance was observed
      between the breeds white giant and gray giant. White giant, gray giant,
      california and soviet chinchilla breeds were in the first cluster of the
      dendrograms. The other breeds: butterfly, black-brown and black-fire constituted
      the second cluster. The gold and silver breeds composed the separate branches.
      The character of localization of the breeds on the dendrograms is in good
      agreement with the real interrelations of the rabbit breeds known from the
      history and genealogy of their formation.

PMID- 8307373
TI  - [Genetic dimorphism in beta-aminoisobutyric acid excretion in patients with
      atherosclerosis of the coronary artery and in groups at risk for atherosclerosis
      in the Lithuanian population].
AB  - Frequency of genetic variants of excretion of beta-aminoisobutyric acid (BAIB) in
      the urea was examined in patients suffering from atherosclerosis of coronary
      arteries and in risk group for atherosclerosis: children frequently suffering
      from respiratory viral infection, children with insulin-dependent diabetes
      mellitus (IDDM) and in adults suffering from IDDM and non-insulin-dependent
      diabetes mellitus. With the aim to determine whether excretion of BAIB could be
      related with CMV persistence of with proteolytic activity of blood serum the IgG
      class antibodies against CMV and level of alpha 1-proteinase inhibitor (alpha 1
      PI) in blood serum was tested also. Frequency of high excretors of BAIB was found
      significantly more often (P < 0.01) in children suffering from virus infection
      compared to that of population. Frequency distribution of BAIB excretion showed
      that "high excretors" were found significantly more often in children suffering
      from atherosclerosis. The difference of BAIB excretion among healthy and
      diabetics was not defined (P > 0.05). The changes of excretion of BAIB in urea
      were not related with quantity of alpha 1-PI in blood serum. Investigation reveal
      a possible relation between high BAIB excretor and latent CMV infection and that
      this may impact atherogenesis. This leads to a suggestion that children who are
      often ill with respiratory virus infection may constitute a risk group for
      coronary atherosclerosis.

PMID- 8307374
TI  - [Ecogenetic aspects of the study of phenotypes and levels of beta-aminoisobutyric
      acid excretion].
AB  - The levels of excretion of beta-aminoisobutyric acid (BAIB) in urea were examined
      in five groups. The distribution of BAIB concentration revealed the existence of
      high and low excretors in each group. Asbestosis patients had the lowest
      frequency of high excretors. The BAIB concentration among high excretors was
      similar for all the groups. The BAIB levels of low excretors varied. The most
      alike were two children groups, asbestosis patients and the workers from the town
      Asbest.

PMID- 8307375
TI  - [Population genetic study of hereditary motor and sensory neuropathy in the Kirov
      region].
AB  - All the cases of hereditary motor and sensory neuropathy (HMSN) in an eastern
      part of Kirov region (Russian north-east) were ascertained (N = 42 including 11
      persons with pre/subclinical forms; m: f = 1). HMSN prevalence is 15.95 +/-
      2.47.10(-5) being higher in rural than in urban populations. The distribution of
      HMSN families (total 16) in 9 districts of the region is uneven. HMSN is the most
      common of all hereditary muscular disorders in the region. Autosomal dominant
      inheritance was established in 12 families, AD gene frequency is 10.90 +/-
      2.90.10(-5) gene penetrance being 90%. Sporadic cases were few (N = 4; 9.76%). No
      proven autosomal recessive or X-linked inheritance was found out.

PMID- 8307376
TI  - [Genetic polymorphism of the sixth (C6) and seventh (C7) components of complement
      in Russian rural inhabitants of the Tomsk region].
AB  - Genetic polymorphism of the sixth (C6) and seventh (C7) components of complement
      revealed by isoelectric focusing among Russian rural inhabitants of the Tomsk
      region was studied. Allele frequencies at the C6 locus are as follows: C6*A =
      0.6250; C6*B = 0.3650, the frequency of the rare alleles is 0.0100. The C7 gene
      frequencies are: C7*1 = 0.9824; C7*2 = 0.0025; C7*3 = 0.0126, with 0.0025 for the
      rare variant.

PMID- 8307377
TI  - [Genetic polymorphism of haptoglobin and quantitative changes in its levels
      during exposure to asbestos].
AB  - The polymorphism and serum levels of haptoglobin were studied in asbestosis
      patients, in the control and the workers exposed to asbest. Hp1-1 has the
      highest, Hp2-2--the lowest and Hp2-1 has the intermediate concentration of this
      protein. In the course of contact with asbest, and especially in asbestosis
      patients, the haptoglobin levels are higher (for all phenotypes). The standard
      deviation from the Hp concentration in asbestosis patients was significantly
      higher. The phenotypes Hp1-1 were found more often in asbestosis patients than
      among asbest-exposed workers.

PMID- 8307378
TI  - [Statistical analysis of the mutagenic efficacy of chronic irradiation at low
      doses in the context of technologic environmental pollution].
AB  - Statistical analysis of natural experimental data's, that be derived in 30-km
      zone of Chernobyl APS to study cytogenetic action of super low doses (0.06-3.30
      cGy in the course of vegetative period) chronic irradiation on combined
      technogenic pollution background, demonstrated that irradiation in this doses
      range does not bring the certain registering contribution in obtaining genetic
      changeability. Significant difference between experimental areas in chromosomal
      aberrations level's, that be established with help boot straep-method, is
      determined apparently by heavy metals genotoxic action.

PMID- 8307379
TI  - [Genetic effects of lead nitrate on seeds of chronically irradiated populations
      of Arabidopsis thaliana].
AB  - The genetic effects of simultaneous treatment of Arabidopsis seeds by the sodium
      lead and low doses of chronic irradiation was studied. It was found that the
      sodium lead is not strongly mutagen and has more toxic effect on biological
      systems. The high lead toxicity is a possible reason of synergetic effects of
      combined treatment with irradiation rays.

PMID- 8307380
TI  - [Statistical validation of a radiation mapping method].
AB  - Correct statistical treatment of results of Goss and Harris experiments on
      radiation hybrid mapping is proposed. Using stochastic simulation a problem of an
      optimal sample size is investigated. Reasons for a repetition of experiments with
      different doses of radiation are discussed.

PMID- 8307381
TI  - [Modification of the mutagenicity of drugs by their immobilization. Effect of
      immobilization of analgin in starch in mice].
AB  - The mutagenic effect of analgin was studied in germ and somatic cells of male
      mice Mus musculus. It was found that injection of analgin (20 and 40 mg per
      mouse) significantly increased the frequency of sperm head anomalies and
      chromosome aberrations in bone marrow cells. Immobilization of analgin in starch
      led to decrease in the drug immobilization.

PMID- 8307382
TI  - Baby boomers: aging population at risk.

PMID- 8307383
TI  - SSRIs could worsen Alzheimer's, anorexia.

PMID- 8307384
TI  - Recommended dosing of ketoprofen clarified.

PMID- 8307385
TI  - Vertebral compression fractures: how to manage pain, avoid disability.
AB  - About 25% of U.S. women over age 50 will suffer one or more vertebral compression
      fractures related to osteoporosis. Vertebral fractures may be biconcave, anterior
      wedge, or crush deformities. A fracture is most often precipitated by putting a
      load on outstretched arms (eg, while raising a window). Back pain is usually
      incapacitating for a few weeks, then diminishes in severity but remains intense
      for 2 to 3 months. Acute complications include transient ileus, urinary
      retention, or (rarely) cord compression. Long-term effects include kyphosis,
      deconditioning, insomnia, and depression. Initial treatment includes bed rest,
      pain management with local and systemic analgesia, bracing to improve comfort,
      and patient reassurance. Long-term management includes spinal stretching
      exercises, walking, and treatment of underlying osteoporosis with calcitonin or
      estrogen in selected patients.

PMID- 8307386
TI  - Chronic lung disease: when to prescribe home oxygen.
AB  - Long-term oxygen therapy has become increasingly common in the treatment of
      hypoxemic patients with chronic lung disease. Its main benefit and indication is
      to prolong survival. Oxygen therapy is also recommended for patients with
      exercise desaturation or sleep desaturation in the presence of hypoxemic
      complications. Some patients may experience improvement in pulmonary
      hemodynamics, exercise duration, work of breathing, sleep, and neurologic
      function. Once a patient meets the criteria for oxygen prescription, you will
      need to complete a medical necessity form and choose from one of three types of
      delivery systems. Your role also includes re-evaluating patients at 1 and 3
      months to determine the need for continuing therapy.

PMID- 8307387
TI  - 30-minute evaluation of incontinence in the older woman.
AB  - The key to successful management of urinary incontinence in the older woman is
      accurate diagnosis of the underlying condition. A simple 30-minute in-office
      evaluation answers the important questions that increase the likelihood of
      reaching the correct diagnosis. This core evaluation includes a history and
      physical exam, urinalysis and other basic lab tests, assessment of urethral
      angulation, and a simple cystometrogram. A patient voiding diary may also help to
      pinpoint the severity of incontinence. Further testing is required if symptoms
      fail to resolve after empiric therapy.

PMID- 8307389
TI  - Meeting highlights. American Geriatrics Society 50th annual scientific meeting,
      New Orleans.

PMID- 8307388
TI  - Physical aspects of aging: is there such a thing as 'normal'?
AB  - Traditional thinking about the process of aging is changing as the distinction
      blurs between normal aging and disease. One of the myths about aging is that all
      older people are alike. However, one of the maxims of geriatrics is that as
      people get older they become less alike. Several models have been proposed for
      the interactions between aging and disease. Although the issue of distinguishing
      normal aging from disease poses challenges in the clinical setting, the inclusion
      of aging into the equation can also make the care of older persons more
      intellectually stimulating.

PMID- 8307390
TI  - Skull trauma in Egyptian and Hippocratic medicine.
AB  - To compare the treatment of skull trauma in Egyptian and Hippocratic medicine,
      the author reviews the pertinent passages of the Smith Papyrus and of the
      Hippocratic Corpus. By examining the treatment of similar cases reported in the
      two documents, it is concluded that the Egyptian physician, with his more
      conservative approach, pursued a more effective and less dangerous course of
      action than the Hippocratic physician, who would aggressively intervene with
      trephination and scraping of the bone.

PMID- 8307391
TI  - [Thoracopagus symmetricus. On the separation of Siamese twins in the 10th century
      A. D. by Byzantine physicians].
AB  - The byzantine author, Leon Diakonos, mentions in 974/975 A.D. a pair of "siamese
      twins", e.g., a thoracopagus symmetricus. He had seen them personally several
      times in Asia Minor when they were about 30 years old. This pair is possibly the
      same that was "successfully" surgically separated after the death of one of the
      twins in the second half of the 10th century in Constantinople. This operation is
      mentioned by two historiographs, Leon Grammatikos and Theodoros Daphnopates.
      Although the second twin survived the operation, he died three days later. In
      spite of its lethal outcome, the operation left a long-lasting impression on the
      historians of that time and was even mentioned 150 years later by Johannes
      Skylitzes. Furthermore, the manuscript of Skylitzes, now in the library of
      Madrid, contains a miniature illuminating this operation. This is likely to be
      the earliest written report of a separation of siamese twins illustrating the
      high standard of byzantine medicine of that time.

PMID- 8307392
TI  - [Medical biography: living fossils and return of the subject].
AB  - Biography, long shunned in the universities, has taken a dazzling revenge since
      the early 1980s--against the "Annales", to be sure, but also under the influence
      of "new history". As regards the history of medicine, the situation remains
      ambiguous. Biography, marrying ethics and progress, has always enjoyed a special
      place in the hearts of traditionalists; the partisans of "problem history"
      consider the genre pre- or ahistoric. However, for the last twenty years several
      authors, fascinated by the richness of individual destinies and anxious to
      transcend their irreducible singularities, have opened up new paths to
      reconciling the individual with anthropological and social history.

PMID- 8307393
TI  - [Surgical intervention against overpopulation: Professor Weinhold's foreskin
      infibulation].
AB  - One of the most bizarre and forgotten suggestions to have developed from the
      discussion of pauperism in the 19th century was the infibulation of the
      impoverished men. A communication in 1827 from the Halle professor of surgery,
      Carl August Weinhold (1782-1829), raised indignation and caused ironic as well as
      angry reactions. Despite such a heated response, Weinhold's proposed method of
      population control soon fell into oblivion, a fate considered by this
      contemporaries as "highly desirable".

PMID- 8307394
TI  - [Experimental data for evaluation of biological effect during exposure to
      chemical and biological factors].
AB  - Joint effects of lysin, eprin and formaldehyde in acute and subacute experiments
      were investigated. As shown, this effect can be evaluated as a partial summing
      with coefficient 1.84.

PMID- 8307395
TI  - [Study of cancerogenic effect of 4-amino-1,2,4-triazole in chronic experiments].
AB  - Results of carcinogenic testing of 4-amino-1,2,4-triazole (AT) in chronic
      experiments is presented. The testing did not reveal carcinogenic properties of
      this substance in rats but showed carcinogenicity in F1 mice. AT can be
      characterized as a substance with limited evidence of carcinogenicity.

PMID- 8307396
TI  - [Hygienic standardization of realon and zinc complex IOMC-1 in water reservoirs].
AB  - Maximum allowable concentrations of Realon and zinc complex IOMC-1 in water were
      recommended at levels, accordingly, 0.04 and 2.0 mg/1 with organoleptic signs of
      action.

PMID- 8307397
TI  - [Rationale for hygienic standards in water of some chemical substances used by
      the pharmaceutical industry].
AB  - Maximum allowable concentrations of 9 half-products of drug synthesis were
      substantiated. Threshold concentrations influencing organoleptic properties of
      substances, selfpurification of water and toxicological effects were determined.

PMID- 8307398
TI  - [Role of various sanitary and hygienic factors in seasonal morbidity of viral
      hepatitis A and acute intestinal infections of unknown etiology in Perm].
AB  - On the territory of town Perm there are some factors of hygienic, climatic and
      technical nature which yearly influence microbial pollution of drinking water and
      seasonal incidence of intestinal infections of obscure etiology. It was shown in
      several years investigations.

PMID- 8307399
TI  - [Quantitative correlation of the content of Campylobacter and sanitary indicative
      bacteria in surface water].
AB  - Quantitative relations between campylobacteria and sanitary indicating bacteria
      in surface waters were studied. A correlation between numbers of campylobacteria
      and lactose-positive bacteria was revealed.

PMID- 8307400
TI  - [Rapid methods for evaluation of hygienic standards of drugs in the air at the
      workplace].
AB  - System of calculating methods for staged prognostication of toxicometric
      parameters and hygienic standards of synthetic drugs was elaborated. This system
      gives possibility to substantiate quantitative criteria for determination of
      capacity and directions of investigations in pharmaceutical industry.

PMID- 8307401
TI  - [Early signs of renal pathology in small intensity chemical exposure].
AB  - Occupational exposure to vapours, gases and aerosols promotes increase of renal
      diseases incidence. Wider use of anamnestic data is recommended during
      preliminary and regular check-ups of this population.

PMID- 8307402
TI  - [Microbial colonization of the caviar of the sturgeon fishes].
AB  - Samples of black caviar in 47.7% of cases are contaminated by opportunistic
      bacteria Aeromonas, Proteus, Vibrio, V. parahaemolyticus. Standardization of
      these micro-organisms content in black caviar is recommended.

PMID- 8307403
TI  - [Food habits of the population in ecologically unfavorable regions].
AB  - Nutrition of population living on the territory polluted after the Chernobyl
      accident is unsatisfactory. Structure of nutrition is inadequate, vitamin
      quantity insufficient. Recommendations on improvement of population nutrition are
      given.

PMID- 8307404
TI  - [Sanitary and microbiologic evaluation of Caspian sprat preserves].

PMID- 8307405
TI  - [Comparison of parameters of physical development in schoolchildren of Moscow and
      Gorno-Altaisk].
AB  - In 1990-1992 a total of 1856 8-15-year-old Russian pupils in Moscow and Gorno
      Altaisk was examined. Chest size of pupils in Moscow were less than in Gorno
      Altaisk. According to our data, this difference became evident in recent years.
      Apparently it is connected with unfavourable social and ecological conditions in
      Moscow.

PMID- 8307406
TI  - [Problems of child health monitoring in connection with environmental factors].
AB  - Analysis of population health is necessary for sanitary and epidemiological
      service. Monitoring scheme is recommended for population health investigation. It
      includes: measuring--analysis--description--modelling--optimization. Computer
      system should be developed for analysis of health data.

PMID- 8307407
TI  - [Hygienic standardization of temperature parameters of sauna effects on pre
      school children].
AB  - Critical temperature (70 degrees C) of hot air exposure of children aged 4-5 was
      determined by physiological investigations. Determination of isothermal skin
      sites of children is useful for hygienic standardization of sauna air exposure.

PMID- 8307408
TI  - [Evaluation of irradiation dosage in the population of the Briansk region by
      determining the plutonium concentration in lung tissue].

PMID- 8307409
TI  - [Evaluation of radon-222 content in the drinking water supplies of the Tula
      region].

PMID- 8307410
TI  - [Hygienic evaluation of a new method of hydrochemical filtration of centralized
      hot water supplies].

PMID- 8307411
TI  - [Characteristics of blood leukocyte interactions in exposure to embryotoxic
      chemical substances in rats].

PMID- 8307412
TI  - [Sanitary and hygienic evaluation of asphalt concrete, manufactured with
      additions of galvanic waste].

PMID- 8307413
TI  - [Hygienic evaluation of microozonizers used for the cleansing of indoor air].

PMID- 8307414
TI  - [International cooperation on the problem of non-contagious diseases].

PMID- 8307415
TI  - [Trends of sanitation and prophylaxis in rural medicine].

PMID- 8307416
TI  - [Thin-layer chromatographic method for determination of N,N-dimethylbenzilamine
      in the air during sanitary and chemical studies of polymers].

PMID- 8307417
TI  - [Methods of evaluation of the validity of experimental studies on the resorptive
      effect of chemical substances on skin in water].

PMID- 8307418
TI  - [Methods of evaluation of animal behavior in sanitary and toxicologic
      experiment].

PMID- 8307419
TI  - [Evaluation of arsenic content in human urine].

PMID- 8307420
TI  - [Psychodiagnostic methods for evaluation and prognosis in the health status of
      the population].

PMID- 8307421
TI  - [Personal monitoring for the evaluation of human exposure to nitrogen dioxide in
      Moscow].
AB  - A method for measuring nitrogen dioxide (ND) individual exposure was developed.
      Levels of ND in lodgings and outside air were measured. On the whole these levels
      were different: in lodging air lower than outside; but if there were gas sources
      in lodgings it was vice versa.

PMID- 8307422
TI  - [Dynamic model of the physical health of the population].

PMID- 8307423
TI  - [Measurement of fluorine in the air].

PMID- 8307424
TI  - [Determination of hydrogen chloride in the air of the workplace in the presence
      of hydrogen bromide].

PMID- 8307425
TI  - [Regional characteristics and practice of sanitary surveillance for the
      protection of centralized drinking water supply of large urban areas].

PMID- 8307426
TI  - [Role of the physician as hygienist in sanitary-epidemiologic service].

PMID- 8307427
TI  - Travellers' diarrhoea.

PMID- 8307428
TI  - Acute fatty liver of pregnancy: a clinical study of 12 episodes in 11 patients.
AB  - Twelve episodes of acute fatty liver of pregnancy (AFLP) were diagnosed in 11
      patients during the past 18 years in a general hospital in Santiago, Chile, with
      a prevalence of 1 per 15,900 deliveries. Acute fatty liver of pregnancy started
      between the 31st and 38th weeks of pregnancy, with malaise, vomiting, jaundice,
      and lethargy as the main clinical manifestations. Polydipsia (in nine episodes)
      and skin pruritus (in seven episodes) were unusual clinical findings. In two
      patients, pruritus started two and four weeks before AFLP, suggesting that an
      intrahepatic cholestasis of pregnancy preceded AFLP in those patients.
      Considering the current prevalence of both diseases in Chile, their association
      should be considered fortuitous. In another patient, two consecutive pregnancies
      were affected by AFLP, raising to three the number of reported patients with
      recurrent AFLP. In 11 episodes, liver biopsies supported the diagnosis of AFLP by
      showing small and midsized vacuolar cytoplasmic transformation as the most
      prominent histopathological feature. Positive intracellular fat staining was
      found in the four samples analysed. Studies by electron microscopy showed
      megamitochondria with paracrystalline inclusions in four samples. All the mothers
      survived, but fetal mortality was 58.3%. Several extrahepatic complications
      delayed maternal recovery for up to four weeks after delivery. This study
      confirms an improvement in maternal prognosis in AFLP, discusses the possibility
      of an epidemiological association with intrahepatic cholestasis of pregnancy, and
      increases the number of patients reported with recurrent AFLP.

PMID- 8307429
TI  - Cigarette smoking and parity as risk factors for the development of symptomatic
      gall bladder disease in women: results of the Royal College of General
      Practitioners' oral contraception study.
AB  - The effects of cigarette smoking and parity on the development of symptomatic
      gall bladder disease remain controversial. These relations have been examined in
      a cohort of 46,000 women followed for up to 19 years during the Royal College of
      General Practitioners' (RCGP) oral contraception study. During follow up, 1087
      women were recorded as experiencing their first ever episode of symptomatic
      cholelithiasis (International Classification of Diseases, 8th revision (ICD-8)
      574) or cholecystitis (ICD-8 575). Smokers were more likely to develop
      symptomatic gall bladder disease than non-smokers (relative risk 1.19; 95%
      confidence intervals (95% CI) 1.06 to 1.34) and there was a significant trend
      with the number of cigarettes smoked daily (test for trend chi 2 = 7.58, p <
      0.01). This relation was most apparent among never users of oral contraceptives,
      although similar trends were found among current and former users. A significant
      direct relation between symptomatic gall bladder disease and parity was also
      found (test for trend chi 2 = 21.89, p < 0.001). When all were examined together
      a trend of increasing risk with lower social class was also found (test for trend
      chi 2 = 5.72, p = 0.02). Current users of oral contraceptives had a moderately
      increased risk of symptomatic gall bladder disease (relative risk 1.15; 95% CI
      0.99 to 1.34), unlike former users (relative risk 1.03; 95% CI 0.90 to 1.18).
      These results suggest that smoking and parity are important risk factors for the
      development of symptomatic gall bladder disease in women.

PMID- 8307430
TI  - Duodenal bile examination in identifying potential non-responders to bile salt
      treatment and its comparison with gall bladder bile examination.
AB  - The results of bile salt treatment in patients with radiolucent stones and a
      functioning gall bladder have been poor. In 42 of these patients awaiting
      cholecystectomy we determined the value of duodenal bile examination in
      predicting gall stone composition, and thus identifying those less likely to
      respond to bile salt therapy. Based on chemical analysis and scanning electron
      microscopy, 28 of 42 (67%) gall stones retrieved at surgery were potentially
      insoluble. Microscopic examination of duodenal bile correctly identified 21 (75%)
      of them: it predicted all four (100%) pigment stones, three of six (50%) calcium
      carbonate containing cholesterol stones, and 14 of 18 (78%) cholesterol stones
      with pigment shells. It was nearly as reliable as microscopic examination of bile
      aspirated directly from the gall bladder during surgery (21 (75%) v 23 (82%); p =
      NS). Furthermore, the presence of cholesterol crystals in duodenal bile was a
      more sensitive indicator than chemical detection of supersaturation (34 of 38
      (89%) v 25 of 35 (71%); p < 0.05) for prediction of cholesterol gall stones.
      Microscopic examination of duodenal bile, if used as a screening test, could help
      to exclude potential non-responders and thereby improve considerably the results
      of oral bile salt treatment for gall stone dissolution.

PMID- 8307431
TI  - Gall stone pulverisation strategy in patients treated with extracorporeal
      lithotripsy and follow up results of maintenance treatment with ursodeoxycholic
      acid.
AB  - Between November 1988 and July 1992 70 patients with radiolucent gall stones were
      treated with extracorporeal lithotripsy (ESL) and ursodeoxycholic acid (UDCA;
      mean (SD) dose 11.2 (1.9) mg/kg/day). Fifty three patients have been followed for
      one year. One week after lithotripsy, 30.6% had completely eliminated all stone
      fragments from the gall bladder and one year later 93.9% were free of stones.
      Three factors were considered important in achieving these results.
      'Pulverisation' of the stone--that is, its fragmentation into echogenic dust
      (crystalline aggregates, some few hundred mu in size) or particles similar to
      grains of sand, smaller than 1 mm in diameter, or both, is required. Secondly,
      dust and particles were rapidly eliminated, strongly suggesting a mechanical
      elimination process by physiological gall bladder contractions. Thirdly, there
      must be chemical dissolution with biliary acids. This therapeutic approach gave
      excellent results without causing any clinically relevant side effects. The first
      20 patients who became free of stones after ESL were given oral bile acid
      maintenance treatment--300 mg/day of UDCA at bedtime, for two years. All were
      asymptomatic and none had suffered a recurrence after two years. In four
      patients, crystalline aggregates, detected in gall bladder bile by ultrasound,
      were subsequently dissolved between one and three months after resuming a full
      dose regimen of UDCA.

PMID- 8307432
TI  - Management of common bile duct stricture caused by chronic pancreatitis with
      metal mesh self expandable stents.
AB  - Twenty patients with chronic pancreatitis and signs of biliary obstruction were
      treated by endoscopic placement of self expandable metal mesh stents, and
      followed up prospectively. Eleven had been treated previously with plastic
      endoprostheses. All had persistent cholestasis, seven patients had jaundice, and
      three overt cholangitis. Endoscopic stent placement was successful in all cases.
      No early clinical complication was seen and cholestasis, jaundice or cholangitis
      rapidly resolved in all patients. Mean follow up was 33 months (range 24 to 42)
      and consisted of clinical evaluation, ultrasonography, and endoscopic retrograde
      cholangiopancreatography (ERCP). In 18 patients, successive ERCPs and
      cholangioscopies have shown that the metal mesh initially embeds in the bile duct
      wall and is rapidly covered by a continuous tissue by three months. The stent
      lumen remained patent and functional throughout the follow up period except in
      two patients who developed epithelial hyperplasia within the stent resulting in
      recurrent biliary obstruction, three and six months after placement. They were
      treated endoscopically with standard plastic stents with one of these patients
      ultimately requiring surgical drainage. No patient free of clinical or
      radiological signs of epithelial hyperplasia after six months developed
      obstruction later. This new treatment could become an effective alternative to
      surgical biliary diversion if further controlled follow up studies confirm the
      initial impression that self expandable metal mesh stents offer a low morbidity
      alternative for longterm biliary drainage in chronic pancreatitis without the
      inconvenience associated with plastic stents.

PMID- 8307433
TI  - Endoscopic sphincteroplasty: a novel and safe alternative to papillotomy in the
      management of bile duct stones.
AB  - Removal of bile duct stones during endoscopic retrograde cholangiopancreatography
      (ERCP) usually includes papillotomy. Papillotomy is associated with occasional
      complications and in addition, the longterm sequelae of papillotomy in young
      patients having laparoscopic cholecystectomy remain unclear. As an alternative to
      papillotomy, this study prospectively evaluated the efficacy and safety of
      endoscopic balloon sphincteroplasty to facilitate bile duct clearance. Of 32
      patients with bile duct stones (diameter 3-30 mm) at ERCP, sphincteroplasty was
      considered inappropriate in four patients because of stone size (> 20 mm)
      necessitating papillotomy for bile duct clearance. Sphincteroplasty was performed
      in the remaining 28 patients to permit duct clearance by dormier basket, balloon
      or mechanical lithotripsy. The bile duct was cleared in 22 patients (79%) while
      additional measures including papillotomy or stent insertion were required in the
      remaining six patients (21%) because of stone size or technical difficulties.
      There was no associated papillary haemorrhage. Pancreatitis was seen in one
      patient (4%) but resolved within 24 hours. Our preliminary experience suggests
      that sphincteroplasty is a safe and effective sphincter preservation technique
      that significantly reduces the necessity for papillotomy in the management of
      bile duct stones.

PMID- 8307434
TI  - Intramural haematoma of the oesophagus complicating sclerotherapy for varices.
AB  - A patient is described who developed an intramural haematoma of the oesophagus
      shortly after variceal endoscopic sclerotherapy. This unusual complication is
      best imaged by computed tomography or nuclear magnetic resonance and needs
      conservative treatment. Resolution usually occurs spontaneously and may result in
      eradication of the varices.

PMID- 8307435
TI  - Multifocal osteonecrosis related to steroid treatment in a patient with
      ulcerative colitis.
AB  - A case of multifocal steroid related osteonecrosis in a patient with ulcerative
      colitis is presented. The pathogenesis, diagnosis, natural history, and treatment
      of the disease is discussed briefly with emphasis on the importance of early
      diagnosis--preferably by magnetic resonance imaging. Early diagnosis often
      depends on the gastroenterologist considering the possibility of osteonecrosis.

PMID- 8307436
TI  - Specialist training in gastroenterology in the European Community: the case for
      European boards. European Board of Gastroenterology.
AB  - Gastroenterological training differs so greatly from country to country in Europe
      it is impossible to believe that training is equally good in each one. This in
      turn, provides a barrier to the free migration of doctors with the European
      Community. These differences also create confusion for migrating patients, and
      call into question the validity of the European Commission directives, which
      pronounce all qualifications obtained in European Community countries to be
      equally acceptable within the community. The European Commission does not have
      the power to unify medical training, but the medical profession itself acting in
      concert as a European body could harmonise the differences to ensure acceptable
      standards of training across the community. The Union of European Medical
      Specialists (UEMS) is the representative body of national medical specialists
      bodies, which reports to the European Commission. The European Board of
      Gastroenterology, a working party of the Gastroenterology Section of the UEMS has
      agreed acceptable and fair standards of training for gastroenterologists, and has
      developed a system for external assessment of training centres and faculty. All
      three, candidates, faculty, and centre would, in the event of a successful
      application, be awarded the European Diploma of Gastroenterology or, in full, the
      Diploma of Recognition of Quality of Training in Gastroenterology. This paper
      discusses these problems, some of their origins, and the proposals of the
      European Board.

PMID- 8307437
TI  - Gall stones and gall bladder motility.

PMID- 8307438
TI  - Resection of the gastric fundus in rats.

PMID- 8307439
TI  - Iron deficiency anaemia.

PMID- 8307440
TI  - Platelet activating factor and Crohn's disease.

PMID- 8307441
TI  - The Nm23 gene and colorectal cancer.

PMID- 8307442
TI  - One week's anti-Helicobacter pylori treatment for duodenal ulcer.
AB  - This open study tested whether eradication of Helicobacter pylori (H pylori)
      heals duodenal ulcers as well as decreasing recurrence. H pylori was detected in
      patients with endoscopic duodenal ulcers by histology, CLO-test, culture, and 13C
      urea breath test (13C-UBT). Tripotassium dicitrato bismuthate (120 mg) and
      amoxycillin (500 mg) each four times daily, were given for seven days, with 400
      mg metronidazole five times a day on days 5-7. The 13C-UBT was repeated
      immediately after treatment and endoscopy repeated within 21 days. After
      treatment unhealed ulcers were reinspected one month later and healed ulcers
      followed up by 13C-UBT alone for 12 months. Of 45 patients, 44 were available for
      follow up. Mean pretreatment excess delta 13CO2 excretion was 25.6 per mil, which
      fell to 2.4 per mil immediately after finishing treatment, indicating clearance
      of H pylori in every patient. At the second endoscopy (median interval 20 days
      from start of treatment) 33 of 44 (75%) duodenal ulcers had healed. Ten of the
      remaining 11 duodenal ulcers were smaller and those 10 healed in the next two
      weeks with no further treatment. Two patients' ulcers that initially healed with
      clearance of H pylori recurred three weeks later (both had metronidazole
      resistant H pylori). H pylori was eradicated in 28 of 44 (64%) patients (13C-UBT
      negative for median follow up 10.2 months). Overall 41 of 43 (93%, 95% confidence
      intervals 81%-99%) duodenal ulcers were healed at one month. This study suggests
      that one week of anti-H pylori triple treatment is effective in healing duodenal
      ulcers.

PMID- 8307443
TI  - Evidence for the essential role of Helicobacter pylori in gastric ulcer disease.
AB  - Helicobacter pylori (H pylori) eradication heals chronic active type B gastritis
      and dramatically changes the natural history of duodenal ulcer disease. There are
      few data concerning the role of anti-H pylori treatment in gastric ulcer disease.
      A total of 83 patients presenting with H pylori positive active gastric ulcer
      disease were treated with omeprazole and antibiotics (amoxicillin, ciprofloxacin,
      roxithromycin) in seven different clinical protocols, each of which included the
      attempt to eradicate H pylori infection and to evaluate the post-therapeutic
      course of ulcer disease. The overall proportion of H pylori eradication was 67.9%
      (53 of 78 patients available for follow up). Best results were obtained with two
      week treatment regimens comprising omeprazole 20 mg twice daily and amoxicillin
      500 mg four times a day or 1000 mg twice daily (eradication > 80%). Eradication
      of H pylori speeds up ulcer healing, with a six week healing rate of 84.9%
      compared with 60% in patients with persistent H pylori infection (p = 0.0148). In
      a subgroup of 11 patients with refractory ulcers, H pylori eradication (n = 10)
      was associated with ulcer healing on continued acid suppression in nine cases.
      One male patient with chronic antral ulcer did not respond to treatment within
      the next six months (H pylori and ulcer persistence), and in one female patient a
      resistant body ulcer was identified as gastric lymphoma. Fifty patients with
      healed ulcers were followed up for one year. Patients with (n = 32) and without
      (n = 18) bacterial eradication had similar demographic and clinical
      characteristics. H pylori eradication was associated with a statistically
      significant reduction of ulcer recurrences (3.1 v 55.6%, p<0.001). This study
      concludes that H pylori eradication considerably changes the natural history of H
      pylori associated gastric ulcer disease. In addition, H pylori eradication speeds
      up ulcers healing and is associated with healing of previously refractory ulcers.
      Thus, treatment aimed at bacterial eradication should be considered in all
      patients with gastric ulcers severe enough to contemplate further treatment
      options.

PMID- 8307444
TI  - Duodenal bacterial overgrowth during treatment in outpatients with omeprazole.
AB  - The extent of duodenal bacterial overgrowth during the pronounced inhibition of
      acid secretion that occurs with omeprazole treatment is unknown. The bacterial
      content of duodenal juice of patients treated with omeprazole was therefore
      examined in a controlled prospective study. Duodenal juice was obtained under
      sterile conditions during diagnostic upper endoscopy. Aspirates were plated
      quantitatively for anaerobic and aerobic organisms. Twenty five outpatients with
      peptic ulcer disease were investigated after a 5.7 (0.5) weeks (mean (SEM))
      treatment course with 20 mg (nine patients) or 40 mg (16 patients). The control
      group consisted of 15 outpatients referred for diagnostic endoscopy without prior
      antisecretory treatment. No patient in the control group had duodenal bacterial
      overgrowth. In the omeprazole group bacterial overgrowth (> or = 10(5) cfu/ml)
      was found in 14 (56%) patients (p = 0.0003). The number of bacteria (log10) in
      duodenal juice in patients treated with omeprazole was distinctly higher (median
      5.7; range < 2-8.7) when compared with the control group (median < 2; range < 2
      5.0; p = 0.0004). As well as orally derived bacteria, faecal type bacteria were
      found in seven of 14 and anaerobic bacteria in three of 14 patients. Bacterial
      overgrowth was similar with the two doses of omeprazole. These results indicate
      that duodenal bacterial overgrowth of both oral and faecal type bacteria occurs
      often in ambulatory patients treated with omeprazole. Further studies are needed
      to determine the clinical significance of these findings, particularly in high
      risk groups during long term treatment with omeprazole.

PMID- 8307445
TI  - Effect of the quaternary ammonium compound trospium chloride on 24 hour jejunal
      motility in healthy subjects.
AB  - This study aimed to record 24 hour jejunal motility in healthy ambulant subjects
      and to analyse changes in motility caused by the oral administration of an
      anticholinergic agent, the quaternary ammonium compound, trospium chloride. In a
      placebo-controlled, double blind crossover trial, 24 hour jejunal motility was
      recorded in 12 healthy volunteers, aged 25 (21-30) years, using a digital data
      logger connected to two strain-gauge transducers mounted 20 cm apart in a
      flexible nasojejunal catheter. A computer program was developed to determine
      contraction parameters. Trospium chloride (15 mg orally thrice daily) prolonged
      the duration of irregular contractile activity after meals (p < 0.02) and reduced
      its contraction frequency and amplitude (p < 0.001). In the fasting state, the
      cycle length of the migrating motor complex was prolonged (p < 0.01) by an
      extended phase I (p < 0.025). Phase III was shortened (p < 0.005) and showed a
      slower aboral migration velocity (p < 0.005). Clustered contractions were less
      frequent during postprandial and fasting periods (p < 0.01). Runs of clustered
      contractions were completely absent with trospium chloride. Digital manometry was
      useful for long term recordings of jejunal motility and enabled the motor effects
      of an anticholinergic agent to be characterised in ambulant subjects.

PMID- 8307446
TI  - Lipid peroxidation and electrogenic ion transport in the jejunum of the vitamin E
      deficient rat.
AB  - Increased concentrations of reactive oxygen species in children with depleted
      antioxidant defences have been implicated in a cycle of malnutrition,
      malabsorption, and infection leading to protracted diarrhoea. A rat model of
      chronic vitamin E deficiency has been used to study the effects of antioxidant
      depletion on jejunal structure and function in vitro. Basal intestinal short
      circuit current (Isc), a measure of net electrogenic ion movement across the
      intestinal epithelium, was greater in chronically vitamin E deficient jejuna than
      controls, as was the electrogenic secretory response to aminophylline and
      Escherichia coli STa but not to bethanechol. The galactose stimulated current was
      also greater in vitamin E deficient jejuna. Indices of lipid peroxidation
      (concentrations of thiobarbituric acid reactive substances and malondialdehyde)
      were increased in the vitamin E deficient small bowel. Small intestinal brush
      border membranes from vitamin E deficient animals displayed changes in both
      static and dynamic components of membrane fluidity measured by steady state
      fluorescence polarography. The results of these studies support the hypothesis
      that oxidative stress in subjects with compromised antioxidant defences results
      in small intestinal hypersecretion, which could predispose to or perpetuate
      protracted diarrhoea.

PMID- 8307447
TI  - Effects of endotoxin and dexamethasone on group I and II phospholipase A2 in rat
      ileum and stomach.
AB  - Phospholipase A2 (EC 3.1.1.4) is a key enzyme in inflammation and is thought to
      play an important part in inflammatory diseases of the gastrointestinal tract. To
      investigate the nature and regulation of phospholipase A2 activity in the
      gastrointestinal mucosa, the distribution of messenger ribonucleic acid (mRNA)
      for group II phospholipase A2 in various parts of the rat gastrointestinal tract
      was studied, as well as the influence of endotoxin or dexamethasone, or both, on
      the group I and II phospholipase A2 mRNA expression and activity in the rat
      glandular stomach and distal ileum. The results show that (a) group II
      phospholipase A2 is present along the whole gastrointestinal tract, but in
      particularly large amounts in the distal ileum, (b) endotoxin increases group II,
      but not group I, phospholipase A2 mRNA expression in the glandular stomach and
      distal ileum, and (c) dexamethasone reduces the endotoxin induced increases in
      group II phospholipase mRNA expression and activity in the gastrointestinal
      mucosa. These findings suggest that phospholipase A2 of type II is a mediator of
      endotoxin effects in the gastrointestinal mucosa and that its expression at the
      mRNA level can be inhibited by corticosteroids.

PMID- 8307448
TI  - Why measure C reactive protein?

PMID- 8307449
TI  - Phenotypic and genotypic variation in Giardia lamblia isolates during chronic
      infection.
AB  - Two Giardia isolates were axenised in vitro after recovery by duodenal aspiration
      from a man with hypo-gamma globulinaemia and chronic giardiasis, before and after
      three unsuccessful courses of metronidazole. In vitro drug sensitivity assays
      showed that the pretreatment isolate was sensitive to metronidazole with minimum
      inhibitory concentration (MIC) and dose that inhibited growth by 50% (ED50)
      values of 0.1 and 0.03 mumol/l, respectively. The post-treatment isolate was 20
      fold more resistant (MIC and ED50 4.3 and 0.58 mumol/l, respectively).
      Differences between these isolates were also found in the surface protein
      profiles after radioiodination, metabolic labelling patterns with 35S-methionine,
      malic enzyme isoenzyme patterns, and by DNA fingerprinting with a M-13
      bacteriophage probe. The phenotypic and genotypic differences between the
      pretreatment and post-treatment isolates suggest that we have isolated two
      different strains from the same patient and that treatment with metronidazole
      resulted in selection of the more resistant strain.

PMID- 8307450
TI  - Immunohistochemical changes in the jejunum in first degree relatives of patients
      with coeliac disease and the coeliac disease marker DQ genes. HLA class II
      antigen expression, interleukin-2 receptor positive cells and dividing crypt
      cells.
AB  - The staining of HLA class II antigens, the presence of cells positive for
      interleukin-2 receptors, the proportion of crypt cells in mitosis in the jejunal
      biopsy specimens, and the dose of coeliac disease marker HLA-DQ genes were
      studied in 75 healthy family members of coeliac disease patients. Eleven had
      silent coeliac disease; in the rest the morphology of the jejunum was normal. In
      the specimens from family members, staining of epithelial cells with HLA-DP and 
      DR antibodies was more widely distributed and stronger than in those from 19
      controls. Interleukin-2 receptor+ cells were seen in the epithelium of all eight
      specimens from subjects with silent coeliac disease, and also in 24
      morphologically normal specimens from family members, but not in the 19 control
      specimens. The proportion of crypt cells in mitosis was increased only in the
      specimens from the subjects with silent coeliac disease. The staining intensity
      of the epithelial cells with HLA-DP and -DR antibodies, the presence of
      interleukin-2 receptor+ cells and the percentage of crypt cells in mitosis were
      significantly associated with the number of coeliac disease marker DQB genes.
      Many family members of patients with coeliac disease have signs of inflammation
      even in morphologically normal jejunum; these inflammatory changes together with
      coeliac disease marker DQ genes may point to latent disease in these subjects.

PMID- 8307451
TI  - Serological screening suggests that adult coeliac disease is underdiagnosed in
      the UK and increases the incidence by up to 12%.
AB  - Because coeliac disease often presents atypically it is underdiagnosed. It is
      suggested that the detection rate may be increased by 12% if serology is used to
      identify cases of occult enteropathy. All adults noted incidentally to be R1 anti
      reticulin antibody (ARA) positive in the course of routine autoantibody testing
      of 6532 sera over one year were followed. None of the eight patients with
      seropositive serum was suspected of having coeliac disease. All eight had high
      titres of IgA anti-gliadin and IgA anti-endomysial antibodies, neither of which
      is detected in a routine autoantibody test, in addition to IgA R1-ARA. On
      clinical review coeliac disease was considered probable in only one patient, but
      because of the strong serological evidence of gluten sensitivity, jejunal biopsy
      was advised in all eight. Seven agreed and all had villous atrophy and crypt
      hyperplasia in keeping with coeliac disease. Six of the seven presented initially
      with vague symptoms such as tiredness or arthralgia. These symptoms disappeared
      after several weeks of gluten withdrawal. Forty two sera showing reticulin
      staining patterns other than R1 were used as controls. Low titre IgA anti-gliadin
      was noted in two of 42 but none had IgA anti-endomysial antibody. These 42 cases
      were not recommended for biopsy. During our study 58 other new adult cases of
      coeliac disease were diagnosed, primarily on clinical rather than serological
      grounds, at the four hospitals that request autoantibody studies. Occult coeliac
      disease detected serologically thus increased the overall incidence of coeliac
      disease by 12% from 58 to 65 cases. R1-ARA, even in the absence of the expected
      symptoms and signs of coeliac disease, is an indication for jejunal biopsy and is
      a reliable indicator of occult coeliac disease.

PMID- 8307452
TI  - Coeliac disease in the elderly.
AB  - Of 228 patients with adult coeliac disease, 42 (19%) were diagnosed aged 60 years
      or over. In this series, of 35 patients who did not have dermatitis
      herpetiformis, 15 had attended family doctors and hospital outpatient departments
      for an average of 28 years with unexplained symptoms or abnormalities in blood
      tests but the diagnosis of coeliac disease had been missed. This is
      unsatisfactory because these patients can both manage and respond to a gluten
      free diet. Thirty eight patients complied strictly with the diet with resolution
      of symptoms. Significant improvement in weight, haemoglobin, albumin, calcium,
      and alkaline phosphatase values after a year on the diet also occurred.
      Clinicians should be alert to the possibility of coeliac disease in the elderly
      particularly in patients with non-specific complaints in the presence of
      unexplained anaemia.

PMID- 8307453
TI  - Intestinal permeability in patients with Crohn's disease and ulcerative colitis
      and their first degree relatives.
AB  - Increased intestinal permeability in patients with Crohn's disease and their
      first degree relatives has been proposed as an aetiological factor. The nine hour
      overnight urinary excretion of polyethyleneglycol-400 (PEG-400) and three inert
      sugars (lactulose, l-rhamnose, and mannitol) was used to test the permeation in
      47 patients with Crohn's disease of whom 18 had at least one first degree
      relative with inflammatory bowel disease (2BD) and 52 patients with ulcerative
      colitis of whom 16 had at least one first degree relative with IBD. A total of 17
      first degree relatives with IBD and 56 healthy first degree relatives were
      included. Thirty one healthy subjects not related to patients with IBD served as
      controls. No significant differences in PEG-400 permeation were found between the
      groups of patients, relatives, and controls, or between diseased and healthy
      relatives. The permeability to lactulose, rhamnose, and mannitol similarly did
      not differ between the three groups. This study challenges the previously
      reported findings of increased PEG-400 permeation in patients with Crohn's
      disease and in their healthy and diseased first degree relatives. There was no
      increase in permeability in a similar group of ulcerative colitis patients and
      their families.

PMID- 8307454
TI  - Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent
      ulcerative colitis.
AB  - The short chain fatty acids, acetate, propionate, and butyrate are produced by
      colonic bacterial fermentation of non-starch polysaccharides. Butyrate is the
      major fuel source for the colonic epithelium and there is evidence to suggest
      that its oxidation is impaired in ulcerative colitis. Triplicate biopsy specimens
      were taken at colonoscopy from five regions of the large bowel in 15 sufferers of
      ulcerative colitis. These patients all had mild or quiescent colitis as assessed
      by clinical condition, mucosal endoscopic and histological appearance. The rate
      of oxidation of glucose, glutamine, and butyrate through to carbon dioxide was
      compared with that in biopsy specimens from 28 patients who had no mucosal
      abnormality. Butyrate (272 (199-368)) was the preferred fuel source for the
      colitic mucosa followed by glutamine (33 (24-62)) then glucose (7.2 (5.3-15))
      pmol/micrograms/hour; medians and 95% confidence intervals, p < 0.01. There was
      no regional difference in the rate of utilisation of these metabolites. In the
      group with colitis the rate of butyrate oxidation to carbon dioxide was
      significantly impaired compared with that in normal mucosa decreasing from 472
      (351-637) pmol/micrograms/hour to 272 (199-368) pmol/micrograms/hour; median and
      95% confidence intervals, p = 0.016. The rate of glucose and glutamine
      utilisation were not significantly different between normal and colitic mucosa.
      These data confirm that in quiescent ulcerative colitis there is an impairment of
      butyrate oxidation.

PMID- 8307455
TI  - Interrelations between interleukin-6, interleukin-1 beta, plasma C-reactive
      protein values, and in vitro C-reactive protein generation in patients with
      inflammatory bowel disease.
AB  - Acute phase proteins are released from the liver in response to cytokines, and
      measurement of serum concentrations offers a valuable means of assessing
      inflammatory bowel disease. C-reactive protein (CRP) is a participating prominent
      component of the acute phase response in active Crohn's disease. This study aimed
      at determining the comparative role of the cytokines interleukin-1 beta (IL-1
      beta) and interleukin-6 (IL-6), in driving CRP production in inflammatory bowel
      disease, and to test the hypothesis that there is a difference in the profile of
      cytokines generated in these two conditions. Serum CRP, the release of the
      cytokines IL-1 beta and IL-6 from monocytes, and the ability of monocyte
      conditioned medium to stimulate CRP synthesis by hepatocytes in an in vitro
      system was measured in patients with ulcerative colitis and Crohn's disease.
      Monocytes from patients with Crohn's disease produced more 1L beta-1 than
      monocytes from patients with ulcerative colitis or normal controls. There was no
      increased tendency for monocytes from Crohn's disease patients to produce more 1L
      6, so the greater circulating values of IL-6 reported by a number of authors in
      Crohn's disease may reflect the participation of a larger number of cells of the
      monocyte-macrophage series, or production of IL-6 by other cell types.
      Correlation of cytokine production by monocytes with in vitro CRP release from
      cultured hepatocytes in response to monocyte conditioned medium showed that, in
      that system, IL-1 beta was the stronger stimulus to CRP production. Some of the
      differences in the inflammatory processes of ulcerative colitis and Crohn's
      disease may reflect differences in the amount of IL-1beta and IL-6 generated from
      macrophages and monocytes.

PMID- 8307456
TI  - Predictive factors of the long term outcome in gastro-oesophageal reflux disease:
      six year follow up of 107 patients.
AB  - There is little information concerning the long term outcome of patients with
      gastro-oesophageal reflux disease (GORD). Thus 109 patients with reflux symptoms
      (33 with erosive oesophagitis) with a diagnosis of GORD after clinical evaluation
      and oesophageal testing were studied. All patients were treated with a stepwise
      approach: (a) lifestyle changes were suggested aimed at reducing reflux and
      antacids and the prokinetic agent domperidone were prescribed; (b) H2 blockers
      were added after two months when symptoms persisted; (c) anti-reflux surgery was
      indicated when there was no response to (b). Treatment was adjusted to maintain
      clinical remission during follow up. Long term treatment need was defined as
      minor when conservative measures sufficed for proper control, and as major if
      daily H2 blockers or surgery were required. The results showed that one third of
      the patients each had initial therapeutic need (a), (b), and (c). Of 103 patients
      available for follow up at three years and 89 at six years, respective
      therapeutic needs were minor in 52% and 55% and major in 48% and 45%. Eighty per
      cent of patients in (a), 67% in (b), and 17% in (c) required only conservative
      measures at six years. A decreasing lower oesophageal sphincter pressure (p <
      0.001), radiological reflux (p = 0.028), and erosive oesophagitis (p = 0.031),
      but not initial clinical scores, were independent predictors of major therapeutic
      need as shown by multivariate analysis. The long term outcome of GORD is better
      than previously perceived.

PMID- 8307457
TI  - Liver disease in ulcerative colitis: an epidemiological and follow up study in
      the county of Stockholm.
AB  - In an epidemiological study of the incidence of ulcerative colitis (UC) in the
      county of Stockholm between 1955 and 1979, 1274 patients with UC were discovered.
      Almost all these patients had regularly been investigated with liver function
      tests; 142 (11%) of them showed signs of hepatobiliary disease. A follow up study
      on all 142 patients with abnormal liver function and UC was made between 1989 and
      1991 to evaluate the cause of the liver abnormality and to find out if the liver
      disease had affected the survival rates. At follow up, eight patients were
      reclassified as having Crohn's disease, 60 had developed normal liver function as
      judged from test results, while the remaining 74 still had signs of hepatobiliary
      disease. The most common explanation for a transient abnormality in liver
      function was active colitis. The temporary signs of liver injury were not
      associated with changes in survival rates for these patients. Infections,
      especially those because of hepatitis B and C virus transmitted by blood
      transfusions accounted for the abnormalities in liver function in 21 patients,
      nine of which had a chronic, but non-fatal course. Twenty nine (2.3%) of the
      patients developed primary sclerosing cholangitis (PSC), and 12 of them died
      during the study period four because of cholangiocarcinoma and eight because of
      hepatic failure; one patient had a transplant. The estimated median time of
      survival from the first presentation of evidence of a liver function, compatible
      with the diagnosis of PSC, to death or liver transplantation was 21 years. A
      comparison of survival rates in patients with UC and patients with UC and
      concurrent PSC showed, a significant reduction in survival in the PSC group
      (p<0.0001). The number of patients with UC who developed PSC remained constant
      during the study period. Thus, although evidence of abnormal liver function is a
      common finding in UC, a spontaneous return to normal levels is common. In this
      study, which did not have a selection bias, the median time of survival among PSC
      patients was far longer than previously described although development of PSC
      among patients with UC does significantly reduce the estimated median time of
      survival.

PMID- 8307458
TI  - Bile acid malabsorption in Crohn's disease and indications for its assessment
      using SeHCAT.
AB  - Patients with Crohn's disease who suffer from longstanding diarrhoea that does
      not respond to conventional treatment pose a common clinical problem. Bile acid
      malabsorption is a possible cause, although its prevalence and clinical
      importance is unclear. This paper explores the clinical indications for referring
      patients with Crohn's disease for bile acid assessment and the extent of bile
      acid malabsorption in this selected group of patients. The selenium labelled bile
      acid SeHCAT was used to assess the effect of disease on the integrity of the
      enterohepatic circulation. Altogether 76% of the patients referred for bile acid
      assessment had longstanding diarrhoea that had not responded to conventional anti
      diarrhoeal treatment or an increase in steroid therapy as their sole or
      predominant symptom. Ninety per cent of patients with bowel resections, almost
      exclusively ileocaecal, had abnormal SeHCAT retention (< 5% at seven days).
      Twenty eight per cent of patients with Crohn's disease who had not undergone
      resection 28% had a SeHCAT retention < 5%, signifying bile acid malabsorption.
      Nineteen of 22 patients given cholestyramine treatment subsequent to the SeHCAT
      test had a good symptomatic response. In conclusion, the prevalence of bile acid
      malabsorption in this selected group with Crohn's disease is sufficiently high to
      justify performing the SeHCAT test in order to separate the various differential
      diagnoses.

PMID- 8307459
TI  - Pathogenesis of gall stones in Crohn's disease: an alternative explanation.
AB  - The increased prevalence of gall stones in Crohn's disease is thought to be
      related to depletion of the bile salt pool due either to terminal ileal disease
      or after ileal resection. This study was designed to examine whether this
      hypothesis is correct and explore alternative explanations. Two hundred and fifty
      one randomly selected patients (156 females, 95 males, mean age 45 years) were
      interviewed and screened by ultrasonography to determine the prevalence of gall
      stones in a large population of patients with Crohn's disease. Sixty nine (28%)
      patients had gall stones proved by ultrasonography (n = 42), or had had
      cholecystectomy for gall stone disease (n = 27). The risk factors for the
      development of gall stones including sex, age, site, and duration of disease, and
      previous intestinal resection were examined by multivariate analysis. Age and
      duration of disease were positive risk factors for gall stones and were
      covariables. The site of disease and of previous intestinal resection did not
      predispose to gall stones. Previous surgery was an independent risk factor for
      the development of gall stones, the risk increasing with number of laparotomies.
      It is suggested that mechanisms other than ileal dysfunction may predispose to
      gall stones. Postoperative gall bladder hypomotility with biliary sludge
      formation may be precursors of gall stone formation in patients with Crohn's
      disease.

PMID- 8307460
TI  - Expression of mutant p53 protein in hepatocellular carcinoma.
AB  - p53 mutations are a common genetic finding in hepatocellular carcinoma from areas
      of high aflatoxin exposure. Recent small studies have shown that p53 gene
      mutations may be less common in areas with a low prevalence of hepatocellular
      carcinoma such as Great Britain. The protein product of mutant p53 can be
      detected immunohistochemically because of its longer half life in comparison with
      native protein. This study used a novel monoclonal antibody DO-7, raised against
      recombinant p53 and effective in routinely processed biopsy specimen tissue, to
      detect the mutant protein in a series of 45 cases of hepatocellular carcinoma
      occurring in white subjects resident in the United Kingdom. Focal nuclear
      labelling was seen in four cases (9%); surrounding cirrhotic tissue in one of
      these was negative for p53 expression. This study shows that p53 mutations are a
      rare event in hepatocarcinogenesis in Great Britain, an area of low aflatoxin
      exposure, and supports the concept of geographical variations in the cause and
      pathogenesis of hepatocellular carcinoma.

PMID- 8307462
TI  - Bone mineral density in coeliac disease.

PMID- 8307461
TI  - Cholera and severe toxigenic diarrhoeas.

PMID- 8307463
TI  - Stimulation and characteristics of secondary oesophageal peristalsis in normal
      subjects.
AB  - The study evaluates the triggering and characteristics of secondary oesophageal
      peristalsis in 25 healthy volunteers. Secondary peristalsis was stimulated by
      rapid intraoesophageal injection of boluses of air and water, and by a five
      second oesophageal distension with a balloon. Air and water boluses triggered
      secondary peristalsis that started in the proximal oesophagus regardless of
      injection site. Response rates were volume dependent with 83% of the 20 ml air
      boluses triggering secondary peristalsis compared with 2% for the 2 ml water
      bolus (p < 0.0001). Response rates for air and water were similar for equal bolus
      volumes and were not influenced by the site of injection. In contrast, balloon
      distension usually induced a synchronous contraction above the balloon, with
      secondary peristalsis starting below the balloon after deflation. The peristaltic
      response rate to balloon distension was also volume dependent and the middle
      balloon was more effective in triggering secondary peristalsis than either the
      upper or lower balloons (p < 0.001). Secondary peristaltic amplitude was less
      than that of primary peristalsis (p < 0.001). Secondary peristaltic velocity with
      a water bolus was slower (p = 0.001) than that of primary peristalsis.
      Intravenous atropine significantly reduced secondary peristaltic responses to all
      stimuli. There was also a significant reduction in pressure wave amplitude for
      air stimulated secondary peristalsis while those for the water responses were
      similar. Secondary peristaltic velocity with air and water boluses was not
      changed by atropine. The reproducibility of testing secondary peristalsis was
      examined six volunteers and did not show any significant differences on separate
      test days in response rate and peristaltic amplitude or velocity. It is concluded
      that in normal subjects, secondary peristalsis can be more reliably triggered by
      intraoesophageal air or water infusion than balloon distension. Secondary
      peristaltic amplitude and velocity are stimulus but not site or volume dependent
      and propagation is partially mediated by cholinergic nerves.

PMID- 8307464
TI  - Strain induced augmentation of upper oesophageal sphincter pressure in children.
AB  - The hypothesis that troublesome oesophagopharyngeal reflux arises from defective
      upper oesophageal sphincter response to straining has been evaluated in 53
      children aged two to 81 months (median 13) referred with symptoms thought to be
      related to gastro-oesophageal reflux. Spontaneously occurring pharyngeal, upper
      oesophageal sphincter, oesophageal body, and gastric pressures were analysed
      after feeding. Inspiratory strain was the most common spontaneously occurring
      strain (172 episodes), defined as an oesophageal body inspiratory negative
      pressure dip at least twice the size of the normal inspiratory wave. Overall,
      during inspiratory strain, upper oesophageal sphincter pressure was significantly
      higher than before straining (p < 0.01) (5 v 27 mm Hg, p < 0.01). Sustained
      strains defined as increases in gastric and oesophageal body pressure for two to
      20 seconds were also common (149 episodes) and when compared with just before
      straining, also augmented upper oesophageal sphincter pressure (60 v 39 mm Hg, p
      < 0.01). The vigour of straining, estimated as increase of gastric pressure,
      correlated significantly with the degree of augmentation of upper oesophageal
      sphincter pressure (p < 0.05). Children with and without evidence of troublesome
      oesophagopharyngeal reflux showed no difference in upper oesophageal sphincter
      response patterns to straining. Failure of augmentation of upper oesophageal
      sphincter tone in the face of strain induced increases of oesophageal body
      pressure is probably a secondary factor in the production of oesophagopharyngeal
      reflux in children.

PMID- 8307465
TI  - Diminished oesophageal traction forces with swallowing in gastro-oesophageal
      reflux disease and in functional dysphagia.
AB  - Relations between primary oesophageal peristaltic amplitude and traction force
      were studied in 30 normal volunteers, 12 patients with functional dysphagia, and
      48 patients with gastro-oesophageal reflux disease, using a new intraluminal
      strain gauge device. Forces generated by swallowing in the normal oesophagus were
      42 (35-60) g (median and interquartile range), a close positive correlation
      existing between traction force and contractile amplitude for each subject (r =
      0.5 (0.38-0.6). Traction force increased with increasing balloon volume from 62
      (50-73) g at 2 ml to 86 (70-105) g at 4 ml (p < 0.05), indicating distension
      related modulation of peristaltic force. Patients with oesophagitis generated
      lower traction forces on swallowing 30 (20-40) g compared with the normal
      subjects (p < 0.01), the degree of impairment being greatest in those patients
      with the most severe mucosal damage. Patients with gastro-oesophageal reflux
      without endoscopic oesophagitis also showed abnormal forces (32 22-38) g p < 0.01
      v controls), which were similar to those patients with mild oesophagitis but were
      greater than those with severe oesophagitis (p < 0.05). In patients with
      functional dysphagia, forces were also impaired (28 (10-60) g p < 0.05 v
      controls) despite normal standard manometry. Our results show that measurement of
      the traction force generated by primary peristalsis provides information about
      oesophageal neuromuscular function that is not demonstrable by manometry alone
      and can be abnormal in patients with oesophageal symptoms in whom standard
      techniques are normal.

PMID- 8307466
TI  - Postprandial antropyloroduodenal motility and gastric emptying in gastroparesis-
      effects of cisapride.
AB  - There is little information about the organisation of antroduodenal contractions
      or pyloric motility in patients with gastroparesis. The mechanisms responsible
      for the acceleration of gastric emptying by cisapride in patients with
      gastroparesis are also poorly understood. Simultaneous manometric and
      scintigraphic recordings were performed in 12 patients with gastroparesis and
      nine healthy volunteers before and after cisapride administration.
      Antropyloroduodenal pressures were recorded with a sleeve/side hole manometric
      assembly and gastric emptying with a scintigraphic method. Thirty minutes after
      the solid component of the test meal had begun to empty from the stomach all
      subjects received 5 mg cisapride intravenously over 10 minutes and recordings
      continued for a further 60 minutes. In the 30 minutes before cisapride there was
      no significant difference in the number of antral pressure waves (median 20 v 33,
      NS), basal pyloric pressure, or the number of isolated pyloric pressure waves
      between patients and volunteers, but the number of antral waves of extent > or =
      6 cm (median 1 v 5, p < 0.05) was less in the patients, as was gastric emptying
      (8% v 20%, p < 0.05). In the patients, there was no change in the number of
      antral waves after cisapride, but there was an increase in the number of antral
      waves > or = 6 cm in extent (median 7 v 1, p < 0.05) and in the rate of gastric
      emptying (26% v 8%, p < 0.01). In the healthy subjects, cisapride increased
      gastric emptying (31% v 20%, p < 0.05), but reduced the number of antral waves
      (10 v 33, p < 0.05). Cisapride had no significant effect on the number of antral
      waves of extent more than or equal to 6 cm (11 v 5, NS). The number of isolated
      pyloric pressure waves decreased after cisapride (4 v 11, p < 0.05). There was a
      relationship between gastric emptying and the number of antral pressure waves of
      extent more than or equal to 6 cm in both the patients (r=0.38, p<0.05) and
      healthy subjects (r=0.05, p<0.01). There was no significant relationship between
      gastric emptying and the number of antral waves. It is concluded that disturbance
      of the relationship between antral, pyloric, and duodenal pressure waves is a
      major abnormality of postprandial gastric motor function in patients with
      gastroparesis. The stimulation of antral pressure waves of extent more than or
      equal to 6 cm may contribute to the acceleration of gastric emptying produced by
      cisapride in patients with gastroparesis and in normal subjects.

PMID- 8307467
TI  - Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite
      production in vivo.
AB  - To determine if reactive oxygen metabolites have a pathogenic role in
      Helicobacter pylori (H pylori) related gastroduodenal disease, this study
      measured their production in antral mucosal biopsy specimens. Two related
      chemiluminescence techniques were used comparing H pylori positive (n = 105) and
      negative patients (n = 64) with a similar spectrum of macroscopic disease. After
      chemiluminescence assays, biopsy specimens were graded histologically. Increased
      luminol dependent chemiluminescence (detecting reactive oxygen metabolites
      through peroxidase catalysed reactions) was found in H pylori positive patients
      (median photon emission = 6.4 x 10(3)/min/mg wet weight (95% confidence intervals
      3.6 to 9.9)) but not H pylori negative cases (-0.9 (-1.3 to -0.6)) (p = 0.0001).
      Similar results were found using lucigenin (which reacts directly with oxygen
      metabolites, particularly superoxide): (H pylori positive 0.9 (0.1 to 3.2); H
      pylori negative -1.2 (-3.4 to -0.6)) (p = 0.0003). Chemiluminescence was greater
      in H pylori positive compared with negative tissue when samples were grouped by
      equivalent macroscopic or microscopic damage. This difference was in part
      accounted for by a greater neutrophil infiltration in the H pylori positive
      mucosa, but when biopsy specimens with equivalent neutrophil infiltration could
      be compared directly, positive specimens gave greater chemiluminescence than
      negative. Smoking, drugs, and alcohol consumption had no independent effect. It
      is concluded that excess mucosal reactive oxygen metabolite production is
      associated with H pylori gastric antral infection and may be an important
      pathogenic mechanism. There is no evidence for reactive oxygen metabolite
      participation in the pathogenesis of gastric mucosal injury in cases unrelated to
      H pylori infection.

PMID- 8307468
TI  - Superior mesenteric artery blood flow and gastric emptying in humans and the
      differential effects of high fat and high carbohydrate meals.
AB  - This study was designed to determine if the differential effect of high fat and
      high carbohydrate meals on mesenteric blood flow is a result of changed gastric
      emptying rate. Eight healthy men were studied twice. Superior mesenteric artery
      blood flow (Doppler ultrasound) was measured before and after a 2.5 MJ meal
      (either 74% of the energy as carbohydrate or 71% as fat). Emptying of meals was
      followed by gamma-scintigraphy. The pattern of the superior mesenteric artery
      blood flow response was different after the two meals (interaction effect p <
      0.001 analysis of variance), with a far more sustained response after fat. The
      time by which half the meal had emptied (t50) was also significantly greater
      after fat (p < 0.02). Superior mesenteric artery blood flow corresponding to t50
      was 449 ml/min after carbohydrate and 592 ml/min after fat. There was a
      significant curvilinear relation between the superior mesenteric artery blood
      flow response and gastric emptying after carbohydrate (r2 = 0.94) and no relation
      at all after fat. This study confirms the finding that ingestion of meals with a
      high fat content slows gastric emptying compared with meals with a high
      carbohydrate content in healthy volunteers. A more sustained mesenteric
      hyperaemia was also recorded after the fat meal compared with the carbohydrate
      meal. The relation, however, between the volume of meal remaining in the stomach
      and the mesenteric response was considerably different after the two meals.
      Further study is required to elucidate the mechanism behind the vascular
      responses recorded in the mesenteric bed after food in humans.

PMID- 8307469
TI  - A database on dyspepsia.
AB  - A prospective study of dyspepsia was carried out in a primary referral hospital
      between 1974-1987 including 1540 patients of whom 1433 were seen as outpatients.
      The study protocol was agreed in advance and a structured questionnaire was used
      to elicit relevant clinical information: up to three diagnoses were permitted for
      each patient. The commonest principal diagnoses were duodenal ulcer (26%),
      functional dyspepsia (22%), and irritable bowel syndrome (IBS) (15%); alcohol
      related dyspepsia (4%) was as common as gastric carcinoma or symptomatic gall
      stones. Multiple diagnoses were common (31% given two diagnoses, and 6% given
      three) so that in all 2111 diagnoses were given to 1540 patients; the functional
      disorders (IBS and functional dyspepsia) considered together accounted for 39% of
      all diagnoses made. Whereas organic conditions were diagnosed by clinicians with
      confidence (63-98% considered 'certain'), even when given as the principal or
      first diagnosis IBS was considered 'certain' in only 61% and functional dyspepsia
      48%. The demographic symptom data, together with information on tobacco and
      alcohol use, and work lost are described in detail.

PMID- 8307470
TI  - Ambulatory small intestinal motility in 'diarrhoea' predominant irritable bowel
      syndrome.
AB  - Dysmotility of the duodenum and proximal jejunum has been reported in patients
      with irritable bowel syndrome. This study extended these findings by recording
      fasting ambulatory motility from electronic strain gauge sensors sited in the
      jejunum and ileum of eight diarrhoea predominant irritable bowel syndrome
      patients and 12 healthy controls. During the day, periodicity of migrating motor
      complexes mean (SEM) did not differ between patients (92 (10) min) and controls
      (85 (7) min). At night, periodicity was shorter in both patients and controls,
      and the daytime dominance of phase II was replaced by phase I. In both groups,
      aboral progression of phase III fronts was associated with a slowing of
      propagation velocity and maximum contractile rate, but an increase in mean
      amplitude of contraction. Discrete clustered contractions were seen in seven
      patients and 10 controls occupying 14 and 16% of daytime phase II activity,
      respectively. Pain episodes were not associated with any specific motility
      patterns. Despite the lack of motility differences between the two groups,
      orocaecal transit time in the irritable bowel syndrome patients was shorter at 57
      (9) min than in the controls, 82 (6) min (p < 0.05). This ambulant study has
      failed to show any abnormalities of fasting small intestinal motility that might
      distinguish diarrhoea predominant irritable bowel syndrome patients from healthy
      controls.

PMID- 8307472
TI  - Tumour necrosis factor and endotoxin synergistically activate intestinal
      phospholipase A2 in mice. Role of endogenous platelet activating factor and
      effect of exogenous platelet activating factor.
AB  - Previous studies have shown that: (a) platelet activating factor induces shock
      and intestinal injury, (b) exogenous platelet activating factor stimulates
      synthesis of endogenous platelet activating factor, and (c) tumour necrosis
      factor alpha and endotoxin synergise to induce shock and bowel injury in animals.
      These last two effects are largely mediated by platelet activating factor forming
      phospholipase A2 A2, a key enzyme for platelet activating factor synthesis, was
      examined in mouse intestine. It was found that tumour necrosis factor alpha and
      endotoxin synergise to stimulate platelet activating factor forming phospholipase
      A2 activity in the intestine, as well as platelet activating factor production,
      and these effects were blocked by pretreatment with platelet activating factor
      antagonists, SRI-63-441 and WEB 2086. In addition, exogenous platelet activating
      factor stimulates intestinal phospholipase A2 activity. These results show that
      tumour necrosis factor alpha and lipopolysaccharide synergistically activate the
      phospholipase A2 that participates in platelet activating factor formation, and
      this activation is largely mediated by endogenous platelet activating factor.
      Furthermore, platelet activating factor itself increases phospholipase A2
      activity, suggesting that platelet activating factor induces its own synthesis,
      probably by phospholipase A2 activation.

PMID- 8307473
TI  - Surgical resections in parous patients with distal ileal and colonic Crohn's
      disease.
AB  - The surgical resection rates among parous women with distal ileal and colonic
      Crohn's disease have been compared with resection rates among distal ileal (n =
      197) and colonic (n = 332) Crohn's disease patients. Thirty of 44 parous women
      with distal ileal Crohn's disease and 28 of 44 with colonic Crohn's disease had
      achieved their first pregnancy on average 8 years and 6.2 years respectively
      before the diagnosis of Crohn's disease was established. Resections for each
      patient were negatively correlated with parity in both groups. (Distal ileal
      disease (p = 0.034, rs = 0.3207), colonic disease (p = 0.051, rs = -0.2960)).
      Patients with distal ileal Crohn's disease and a history of pregnancy at
      diagnosis (n = 30, mean follow up = 15 years) had fewer resections/patient when
      compared with the published resection group: mean (SD); 1.17 (0.65) v 1.57
      (1.05), p = 0.006. Patients with colonic Crohn's disease and a history of
      pregnancy at diagnosis (n = 28, mean follow up = 16.5 years) had fewer
      resections/patient when compared with the published resection group: mean (SD);
      0.68 (0.77) v 1.05 (0.77), p = 0.019. In summary, patients with distal ileal and
      colonic Crohn's disease, who had been pregnant in the past subsequently need
      fewer surgical resections. Pregnancy could influence the natural history of
      Crohn's disease either by decreasing immune responsiveness or by retarding
      fibrous stricture formation, which is the commonest indication for surgical
      intervention.

PMID- 8307471
TI  - Absorption of a hypotonic oral rehydration solution in a human model of cholera.
AB  - The development of oral rehydration solutions (ORSs) has been one of the
      important therapeutic advances of this century. The optimal formulation, however,
      of ORSs for both cholera and other infective diarrhoeas is still debated. Part of
      the problem in developing ORSs has been the lack of adequate test systems for the
      assessment of new formulations before clinical trial. We have developed a jejunal
      perfusion, cholera toxin induced, secretory model in humans and have compared net
      water and solute absorption from a hypotonic ORS (HYPO-ORS: sodium 60 mmol/l,
      glucose 90 mmol/l, osmolality 240 mOsm/kg) and the British Pharmacopoeia
      recommended ORS (UK-ORS: sodium 35 mmol/l, glucose 200 mmol/l, osmolality 310
      mOsm/kg) in six healthy volunteers. A plasma electrolyte solution (PES) was also
      perfused in all subjects to confirm a secretory state. Only HYPO-ORS reversed
      sodium secretion to absorption (p < 0.01). Both ORSs promoted net water
      absorption but this was greatest with HYPO-ORS (p < 0.01). Glucose and potassium
      absorption rates were similar for both ORSs whereas chloride absorption mirrored
      sodium absorption and was greatest from HYPO-ORS (p < 0.05). These results, in a
      biologically relevant model of secretory diarrhoea, suggest it may be possible to
      achieve improved rates of rehydration by the use of hypotonic ORS with mid range
      sodium concentrations.

PMID- 8307474
TI  - Enzyme linked immunosorbent assay (ELISA) and immunoprecipitation studies on anti
      goblet cell antibody using a mucin producing cell line in patients with
      inflammatory bowel disease.
AB  - Circulating anti-goblet cell antibody and its corresponding antigen in patients
      with inflammatory bowel disease were investigated. Anti-goblet cell antibody in
      the serum was examined by immunocytochemistry and enzyme linked immunosorbent
      assay (ELISA), using a colonic cancer cell line, HT29-18-N2, which differentiates
      into intestinal goblet cells. The frequencies of anti-goblet cell antibody
      detected by immunocytochemistry were 14 in 48 patients with ulcerative colitis
      (29%) and five in 15 patients with Crohn's disease (33%). By ELISA, the
      frequencies of anti-goblet cell antibody were 38% in ulcerative colitis and 33%
      in Crohn's disease. This antibody did not relate directly to anti-neutrophil
      cytoplasmic antibodies (ANCA), although the serum samples positive for anti
      goblet cell antibody were commonly positive for ANCA in ulcerative colitis.
      Immunoprecipitation and SDS polyacrylamide gel electrophoresis (PAGE) study
      showed that the antibody in the ELISA positive serum samples recognised a > 200
      kD goblet cell antigen, which remained unchanged after reduction, indicating that
      it consists of single chain polypeptides. These results suggest that there is a
      subgroup of inflammatory bowel disease that has circulating anti-goblet cell
      antibody reactive with a > 200 kD antigen. The antibody detected by newly
      established ELISA will be a disease marker for this group and the identification
      of the corresponding antigens may be important for the understanding of the
      underlying immune abnormalities.

PMID- 8307476
TI  - Pouchitis--recurrence of the inflammatory bowel disease?
AB  - The incidence and characteristics of reservoir inflammation after restorative
      proctocolectomy for ulcerative colitis were studied in a series of 179 patients.
      The median follow up time was 27 months (range 6-80). Pouchitis occurred in 36
      patients (20%) and nine of these (5%) developed a chronic, persisting pouchitis.
      There were no pouch failures as a result of pouchitis and no significant adverse
      effect on longterm functional outcome. The overall cumulative risk to develop
      pouchitis four years after surgery was 23%. The risk of pouchitis is
      unpredictable on clinical grounds except that there were significantly less
      patients with left sided colitis in the group who subsequently developed
      pouchitis. Morphological and histochemical studies showed a greater degree of
      colonic metaplasia in the pouch mucosa in patients with pouchitis and patients
      with a chronic pouchitis had the highest degree of changes. The results support
      the view that pouchitis is a novel manifestation of inflammatory bowel disease in
      ileal mucosa that has changed slowly to a colon like mucosa.

PMID- 8307475
TI  - Faecal diversion for Crohn's colitis: a model to study the role of the faecal
      stream in the inflammatory process.
AB  - The high incidence of clinical remission after faecal diversion for Crohn's
      colitis suggests the faecal stream may play a part in the inflammatory mechanism.
      The effect of faecal diversion (n = 22) and restoration of intestinal continuity
      (n = 10) was assessed in patients with Crohn's colitis and compared with
      controls. Faecal diversion produced significant improvement in the disease
      activity index mean (SEM) (before 176 (9); after 114 (9), p < 0.01) and serum
      albumin concentrations (before 33 (3.0); after 38 (3.0), p < 0.05) in all
      patients with Crohn's colitis. The crypt cell production rate (CCPR) was
      maintained after faecal diversion for Crohn's colitis but fell in the control
      group (before = 3.6 (0.8)), at two (1.4 (0.4), p < 0.02), and six weeks (1.6
      (0.4), p < 0.05). Mucosal glucosamine synthetase activity, reflecting
      glycoprotein synthesis, was significantly lower in patients with Crohn's colitis
      (analysis of variance p < 0.05) after diversion but was maintained in the control
      group. Restoration of intestinal continuity failed to produce reciprocal changes.
      The sustained cellular proliferation and fall in glycoprotein synthesis in
      Crohn's colitis after faecal diversion may represent the end of an exaggerated
      protective response and regenerative hyperplasia after exclusion of the faecal
      stream. This study suggests the faecal stream may participate in the inflammatory
      process in Crohn's colitis. The underlying mechanism is unknown.

PMID- 8307477
TI  - Effect of nicotine on rectal mucus and mucosal eicosanoids.
AB  - Because ulcerative colitis is largely a disease of non-smokers and nicotine may
      have a beneficial effect on the disease, the effect of nicotine on rectal mucosa
      in rabbits was examined. Nicotine was given subcutaneously by an Alzet mini-pump
      in doses of 0.5, 1.25, and 2 mg/kg/day for 14 days to three groups of eight
      animals and compared with eight controls. Mean (SD) serum nicotine concentrations
      (ng/ml) were 3.5 (1.1), 8.8 (2.3), and 16.2 (5.2) respectively in the treated
      groups. The thickness of adherent mucus on rectal mucosa in controls (median 36
      microns) was significantly reduced by low dose (22 microns, p = 0.0011), and
      increased by high dose nicotine (48 microns, p = 0.035). Incorporation of
      radioactive glucosamine into papain resistant glycoconjugates was unchanged,
      indicating that mucin synthesis was unaltered. Prostaglandins (PG) were reduced,
      in some cases significantly (6-keto PGF1 alpha, PGF2 alpha, and hydroxy
      eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence-
      with greatest inhibition in relation to the lowest dose. Nicotine, and possibly
      smoking, may affect colitis by an action on mucosal eicosanoids and on adherent
      surface mucus secretion in the rectum and large bowel.

PMID- 8307478
TI  - Effects of biofeedback on obstructive defecation--reconditioning of the
      defecation reflex?
AB  - Twenty two patients with obstructive defecation were recruited for relaxation
      training by domiciliary self regulatory biofeedback. Each patient served as his
      or her own control for anorectal and proctographic assessments. Biofeedback
      training improved the obstructive symptoms of the patients and showed significant
      change in various parameters related to the obstructive defecation syndrome. As
      examined by isotope dynamic proctography: the defecation rate (% of
      evacuation/defecation time) was significantly increased (p < 0.05), the anorectal
      angles at rest and during attempted defecation were made more obtuse (p < 0.05),
      and the pelvic floor movements were made more dynamic on voluntary contraction of
      the anal sphincter (p < 0.03). The external anal sphincter electromyographic
      voltage recorded during defecation was significantly reduced (p < 0.0005) as was
      the surface anal plug electromyographic electrode voltage (p < 0.0001), which was
      associated with a greatly reduced anismus index (p < 0.0001). The rectal
      sensation was improved (p < 0.05), concomitantly. Biofeedback thus improves the
      defecation act in patients suffering from inappropriate contraction of the pelvic
      floor and sphincter musculature. Furthermore, this study has shown that
      biofeedback objectively influences the defecation reflex leading to an improved
      quality of higher control of bowel function.

PMID- 8307479
TI  - Longterm outcome after injection sclerotherapy for oesophageal varices in
      children with extrahepatic portal hypertension.
AB  - A consecutive series of 36 children with bleeding from oesophageal varices
      secondary to extrahepatic portal hypertension was successfully treated by
      endoscopic injection sclerotherapy and followed up over a mean period of 8.7
      years after variceal obliteration. There were no deaths from portal hypertension
      or its treatment and morbidity related to oesophageal sclerotherapy was minimal.
      Endoscopic injection sclerotherapy alone proved safe and effective in controlling
      variceal bleeding from portal hypertension in over 80% of the children. Recurrent
      variceal bleeding developed in 10 (31%) patients but half of these were
      effectively treated by further sclerotherapy. Gastric variceal bleeding
      unresponsive to sclerotherapy necessitated successful portosystemic shunt surgery
      in four (13%) patients. Two children required splenectomy for painful
      splenomegaly. In most children injection sclerotherapy is the best treatment for
      the primary management of bleeding oesophageal varices, reserving portosystemic
      shunting or other surgical procedures for those with bleeding from
      gastrointestinal varices.

PMID- 8307480
TI  - Antimitochondrial antibody negative primary biliary cirrhosis: a distinct
      syndrome of autoimmune cholangitis.
AB  - This study reports on a group of 20 patients with an initial diagnosis of primary
      biliary cirrhosis (PBC) whose serum tested negative for antimitochondrial
      antibodies by immunofluorescence. All had a clinical history compatible with
      primary biliary cirrhosis, and results of biochemical, histological, and
      radiological investigations were consistent with this diagnosis despite the
      absence of antimitochondrial antibodies by immunofluorescence. For comparison,
      these patients were matched for sex and serum bilirubin with 20 antimitochondrial
      antibody positive (> 1:160) and histologically confirmed primary biliary
      cirrhosis patients who served as controls. Serum samples from both groups were
      retested blindly for antimitochondrial antibodies using immunoblotting and for
      antibodies to the major M2 mitochondrial autoantigens by enzyme linked
      immunosorbent assay (ELISA). Three antimitochondrial antibody immunofluorescence
      negative patients had antimitochondrial antibodies by immunoblotting and ELISA;
      the remaining 17 patients were confirmed negative by all methods. The
      antimitochondrial antibody immunofluorescence positive controls were verified by
      immunoblotting or ELISA, or both. All 17 patients negative for antimitochondrial
      antibodies had antinuclear antibodies, often in high titres, compared with 3/17
      of the antimitochondrial antibody positive controls (p = 0.0001). Additionally,
      the antimitochondrial antibody negative group also had significantly higher
      smooth muscle antibody titres (p = 0.03) and lower serum IgM (p = 0.01) and
      aspartate aminotransferase (p = 0.03) activities than the antimitochondrial
      antibody positive controls. Analysis of clinical findings, histological tests,
      serum bilirubin, alkaline phosphatase, alanine aminotransferase, and IgG,
      disclosed no significant differences between the two groups. This paper describes
      a group of patients with the clinical and histological features of PBC but who do
      not fulfil the usual criteria necessary to make this diagnosis. Because they also
      have very high titres of antinuclear antibodies, smooth muscle antibodies, and
      comparatively low IgM and aspartate aminotransferase activities, we believe they
      are distinct from PBC and have a syndrome of autoimmune cholangitis.

PMID- 8307481
TI  - Expression of glutathione S-transferases in normal and malignant pancreas: an
      immunohistochemical study.
AB  - The glutathione S-transferases (GSTs) are a family of detoxification and
      metabolising enzymes, which have been linked with the susceptibility of tissues
      to environmental carcinogens and resistance of tumours to chemotherapy.
      Environmental carcinogens have been implicated in the pathogenesis of pancreatic
      carcinoma, which is also a tumour characterised by marked chemotherapeutic drug
      resistance. In this study 26 pancreatic adenocarcinoma and 12 normal pancreatic
      samples were examined immunohistochemically for expression of pi (acidic), alpha
      (basic), and mu (neutral) GST. Fourteen (54%) of the tumours expressed pi GST
      alone, two (8%) expressed both pi and alpha GST, and two (8%) showed
      immunoreactivity with alpha GST alone. In the normal pancreas the intralobular
      ducts and centroacinar cells expressed pi GST alone whereas the large ducts
      expressed both pi and alpha GST. The acinar cells showed immunoreactivity only
      with anti-alpha GST. Mu GST was not expressed by normal or malignant pancreas.
      Expression of pi GST by pancreatic carcinoma may be a marker of the malignant
      phenotype and be induced during neoplastic transformation. Alternatively it could
      possibly reflect cell of origin, suggesting that the tumour arises from the
      centroacinar cells or intralobular ducts, or both rather than the large ducts.

PMID- 8307482
TI  - Cholecystokinin type B receptor antagonist PD-136,450 is a partial secretory
      agonist in the stomach and a full agonist in the pancreas of the rat.
AB  - Gastrin (cholecystokinin type B (CCK-B)) receptor antagonists may help to
      elucidate the physiological role of gastrin, have therapeutic potential as acid
      antisecretory drugs, and may be of use as adjuvant therapy for gastrin sensitive
      tumours. In binding studies, the gastrin receptor antagonist PD-136,450 had at
      least 1000 fold greater affinity for gastrin (CCK-B) than CCK-A receptors. In
      this study the biological activity of PD-136,450 was evaluated in conscious and
      anaesthetised rats. PD-136,450 antagonised gastrin stimulated acid secretion
      after subcutaneous (IC50: 0.28 mumol/kg; conscious rats) and intravenous (IC50:
      0.17 mumol/kg; anaesthetised rats) administration. In basal secreting fistula
      animals, the compound stimulated acid output to 30 (5)% of the maximal response
      to gastrin. Stimulant activity was not caused by gastrin release. As an agonist
      PD-136,450 was about 350 times less potent than gastrin-17 on a molar basis. In
      addition, PD-136,450 was a powerful agonist of pancreatic secretion in
      anaesthetised rats. The specific gastrin antagonist L-365,260 inhibited the
      (partial) agonist activity of PD-136,450 in the stomach and the specific CCK-A
      receptor antagonist L-364,718 inhibited the agonist activity of PD-136,450 in the
      pancreas. It is concluded that the agonist effect of PD-136,450 is mediated via
      interaction with the gastrin (CCK-B) receptor in the stomach and the CCK-A
      receptor in the pancreas.

PMID- 8307484
TI  - Crohn's disease and myasthenia gravis: a possible role for thymectomy.
AB  - A female patient with a three year history of Crohn's disease of the colon
      developed myasthenia gravis. Despite diversion of the faecal stream by an
      ileostomy, and total colectomy, the patient had continuing problems with perineal
      and perianal abscesses and fistulas. Her myasthenia gravis became unresponsive to
      anti-cholinergics so a thymectomy was performed. The perineal and perianal
      disease improved subsequently. This case supports the theory that functional
      disturbances of the thymus may have a role in the pathogenesis of inflammatory
      bowel disease.

PMID- 8307483
TI  - Argyrophil cell hyperplasia and a carcinoid tumour in the stomach of a patient
      with sporadic Zollinger-Ellison syndrome.
AB  - In the rat, hypergastrinaemia induced by drug treatment with omeprazole or potent
      H2-receptor antagonists leads to the development of gastric enterochromaffin-like
      cell carcinoids. In man, gastric carcinoids induced by hypergastrinaemia have
      been described only in patients with chronic atrophic gastritis type A and in
      patients with the multiple endocrine neoplasia syndrome type 1. This patient with
      Zollinger-Ellison syndrome without gastric mucosal atrophy and without evidence
      of the multiple endocrine neoplasia syndrome developed an argyrophil gastric
      carcinoid tumour. This observation indicates that hypergastrinaemia in the
      sporadic Zollinger-Ellison-syndrome may induce gastric carcinoids.

PMID- 8307485
TI  - Pulmonary hypertension associated with primary biliary cirrhosis in the absence
      of portal hypertension: a case report.
AB  - Pulmonary hypertension is well described in association with portal hypertension
      of any cause including end stage primary biliary cirrhosis (PBC). The essential
      feature of this association is the presence of portosystemic shunting, including
      surgically created shunts. A patient with primary pulmonary hypertension and PBC
      without portal hypertension is reported. This suggests that primary pulmonary
      hypertension may be associated with PBC in the absence of portal hypertension.
      Decisions regarding appropriate organ transplantation may depend on whether
      pulmonary hypertension is primary or secondary to portal hypertension.

PMID- 8307486
TI  - Towards safer endoscopic retrograde cholangiopancreatography (ERCP)

PMID- 8307487
TI  - Location of superoxide anion in the human colonic mucosa.

PMID- 8307488
TI  - Selective affective biasing in recognition memory in the irritable bowel
      syndrome.

PMID- 8307489
TI  - Left sided colon cancer.

PMID- 8307490
TI  - Alcohol v epinephrine and polidocanol.

PMID- 8307491
TI  - Oroileal transit of 5-aminosalicylic acid.

PMID- 8307492
TI  - Tumor necrosis factor and platelet activating factor in stool during
      salmonellosis.

PMID- 8307493
TI  - Bile duct injury after laparoscopic cholecystectomy.

PMID- 8307494
TI  - Yes, there are sexual problems. Now, what can we do about them?

PMID- 8307495
TI  - Sexuality among gynecologic cancer patients--a cross-sectional study.
AB  - To establish the prevalence of sexual activity among gynecologic cancer patients
      and to estimate the extent of sexual problems, a cross-sectional study using
      questionnaires was used. All patients (pts) had gynecologic cancer treated with
      chemotherapy or radiation therapy and attended the gynecologic outpatient
      department at Rigshospitalet, Copenhagen from December 1, 1989 to January 31,
      1990; 146/186 (78%) pts participated. The study describes the 107/146 (74%) pts
      who had a partner. Median ages for pts with endometrial, cervical, and ovarian
      cancers were 63, 55, and 52 years, respectively. The median time since diagnosis
      was 15 months (range, 0-311 months). Little or no desire for sexual relations was
      found among 74% of the patients and 42% of their partners, but 54% of the
      patients were sexually active, 79% of the patients < 55 years old, and 37% of the
      patients > 55 years old. Sexual activities were not related to diagnosis or stage
      of disease. Among the sexually active patients 40% experienced dyspareunia. Only
      22% of all patients with a partner expressed dissatisfaction with their sexual
      life or lack thereof. Despite considerable decrease in sexual desire and frequent
      dyspareunia, many gynecologic cancer patients continue to be sexually active.
      Gynecologic cancer patients of all ages should be supplied with information on
      the possible sexual changes their disease may evoke, but they should also be
      reassured that many patients regain their sexual capacity and satisfaction.

PMID- 8307496
TI  - A phase II study of intraperitoneal carboplatin as adjuvant treatment in early
      stage ovarian cancer patients.
AB  - In a previously reported phase I study of carboplatin administered ip to patients
      with ovarian cancer at our clinic, it was determined that the recommended dose
      for phase II was 500 mg/m2. In this study, this dose was given to 47 patients
      with the purpose of determining the relapse-free interval and toxicity. Four
      courses were given with a 28-day interval in an escalated fashion. Median age of
      patients was 55 years. Karnofsky index was 100 in 98% of the patients. Thirty-one
      patients had FIGO stage I and 16 patients had FIGO stage II ovarian cancer.
      Median time to recurrence has not yet been reached among 43 evaluable patients
      after a median (range) follow-up time of 26.2 (5.5-45.9) months. Recurrent
      disease was documented in 10 patients (23%). The relapse site was intraabdominal
      in 7 and extraabdominal in 1 patient. Two patients had combined intra- and
      extraabdominal relapse sites. Thirty-six of 43 patients went through second-look
      surgery. The total number of treatment cycles given to evaluable patients was
      154. In the patient group with relapsed tumor, > or = 3 courses were administered
      to 60%, whereas nonrelapsed patients had > or = 3 courses in 94% (P = 0.019). The
      reason for this distribution was higher toxicity and more frequent catheter
      related problems in patients with relapsed tumor. Median (range) disease-free
      interval for relapsed patients was 11.5 (5.5-26.6) months. Myelosuppression,
      especially thrombocytopenia, was the dose-limiting systemic toxicity. The overall
      hematologic toxicity (all courses) was median (range) WBC 3.9(0.3-25.0) x
      10(9)/liter, PLTC 212(7-961) x 10(9)/liter, and Hb 109(75-153) g/liter. WHO grade
      4 toxicity for WBC was observed in 6.7%, for PLTC in 17.8%, and for Hb in 0% of
      the patients. Day to nadir values for WBC, PLTC, and HB were in median (cycle 1
      4) 18, 16, and 18 days, respectively. Subjective toxicity was mild. In
      conclusion, ip carboplatin as a single-agent drug in first-line adjuvant
      chemotherapy of early-stage ovarian cancer has shown moderate activity. The
      administered dose in this study was safe, with acceptable toxicity.

PMID- 8307498
TI  - Estrogen and endometrial cancer: an epilogue a la recherche du temps perdu.

PMID- 8307497
TI  - GnRH agonist therapy in human ovarian epithelial carcinoma (OVCAR-3)
      heterotransplanted in the nude mouse is characterized by latency and transience.
AB  - We have previously documented the responsiveness of a cell line of human ovarian
      epithelial carcinoma (Bowman Gray 1) heterotransplanted in nude mice to treatment
      with the GnRH agonist Lupron-SR. In this study we used another human ovarian
      epithelial carcinoma cell line, OVCAR-3, and the human endometrial carcinoma cell
      line HEC-1A. After a latent period, OVCAR-3 tumors showed significant inhibition
      of growth on Days 17, 21, and 24 (P < 0.03) compared to controls. The effect was
      transient and did not persist beyond Day 24. HEC-1A tumors showed no inhibition
      of growth. Radioreceptor assay studies utilizing native radiolabeled GnRH and [D
      Lys6]-GnRH revealed no specific GnRH receptors in any of the tumor samples (BG-1,
      OVCAR-3, HEC-1A, University of Nebraska cell line, and two fresh human ovarian
      epithelial tumor samples) compared to male rat anterior pituitary cells. Binding
      studies and the latency and transience of effect would suggest that the mechanism
      of action in this animal model may be indirect. This activity may be via altered
      circulating steroids, gonadotropins, cell-cycle regulatory events, or some other
      as-yet-undefined action related to GnRH agonist administration or indirectly via
      effects of the metabolic products of degraded GnRH agonist such as D-amino acids,
      which are incorporated into the cells by constitutive or adsorptive pinocytosis.
      This study confirms latency and transience of effect of GnRH agonist therapy on
      an in vivo model of ovarian cancer.

PMID- 8307499
TI  - Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial
      neoplasia (CIN).
AB  - A spectroscopic system incorporating a pulsed nitrogen laser, an optical fiber
      probe, and an optical multichannel analyzer was utilized to record fluorescence
      spectra of the intact cervix at colposcopy. Spectra were obtained from 66
      colposcopically normal areas and 49 histologically abnormal areas (5 pathologic
      inflammation, 21 HPV infection, 9 CIN I, 10 CIN II, and 4 CIN III) in 28
      patients. The resulting spectra could be used to differentiate histologically
      abnormal tissues from colposcopically normal tissues with a sensitivity,
      specificity, and positive predictive value of 92, 90, and 88%. Furthermore, CIN
      could be differentiated from nonneoplastic abnormal tissues with a sensitivity,
      specificity, and positive predictive value of 87, 73, and 74%. These results
      suggest that laser-induced fluorescence can be used in the recognition and
      differential diagnosis of CIN at colposcopy.

PMID- 8307500
TI  - Who finds cervical laser therapy painful?
AB  - To identify women who find outpatient laser cervical surgery painful we designed
      a prospective observational study correlating surgical pain with multiple
      variables. The pain scoring systems were validated by comparing the subjective
      linear analogue score with an objective scoring method. The pain of surgery was
      compared with age, parity, acute anxiety scores, psychological state,
      premenstrual syndrome scores, phase of the menstrual cycle, contraceptive use,
      menstrual history, nature of the lesion, and intraoperative bleeding. Anxious
      women with no children suffered most. Nulliparity, acute preoperative anxiety,
      and a history of dysmenorrhea independently predict high pain scores. Young women
      and those using the combined oral contraceptive pill also find laser surgery more
      painful but this is because they are less likely to have delivered children and
      more likely to suffer from dysmenorrhea. Psychological state, premenstrual
      syndrome score, phase of the menstrual cycle, type of surgery, and perioperative
      bleeding have no predictive value. We suggest that nulliparous women and
      dysmenorrhea sufferers who are anxious about outpatient surgery but ambivalent
      about hospital admission should be offered cervical surgery under general
      anesthesia. Parous women who do not suffer from dysmenorrhea can be reassured
      that outpatient laser treatment should be tolerable.

PMID- 8307501
TI  - Granulosa cell tumors of the ovary: prognostic factors and outcome.
AB  - Granulosa and theca cell tumors of the ovary account for 2-3% of ovarian
      malignancies. This study includes 54 patients with the diagnosis of granulosa
      cell tumors of the ovary treated between 1953 and 1987. Median age at diagnosis
      was 57 (27-83) years. The lesions were staged according to FIGO. The number of
      patients in various stages was IA, 41; IB, 3; IC, 3; IIB, 6; and III, 1. Median
      tumor size, 11 cm; range, 0.5-30 cm. Post-menopausal bleeding was diagnosed in
      48%, MHC in 37%, proliferative endometrium in 32%, and atypia of endometrial
      cells in 13% of the cases. Fifty patients were treated with primary surgery, 48
      patients were treated with adjuvant external radiotherapy, and 3 patients
      received complementary chemotherapy. The survival rates in stage I were 94 and
      88% after 5 and 10 years, respectively, and in stages II-III were 44% after 5 and
      10 years. Overall survival was 90% at 5 years. The frequency of observed mitosis
      influenced the survival rate: with less or equal 4/10 HPF the survival was 100%
      in 5 years, with 5-9/10 HPF the survival was 80% in 5 years with a median
      survival time of 9 years, and with more or equal 10/10 HPF the longest survival
      was 4 years. At the end of the study, 45 patients (83%) are alive with no
      evidence of disease, 1 patient is alive with disease, 4 patients are dead of
      recurrent disease, and 4 patients are dead from intercurrent disease. Endometrial
      carcinoma was detected in 5 patients. The total survival is better than that with
      epithelial ovarian cancer as the hormonal symptoms make an early diagnosis
      possible. Stage for stage the survival is equal. There is an increased incidence
      of endometrial carcinoma and concomitant other malignancies. The mitotic rate is
      a well-defined parameter and influences the survival significantly and should be
      considered the most important prognostic factor at treatment planning.

PMID- 8307502
TI  - A multivariate analysis of clinicopathologic factors for predicting outcome in
      uterine sarcomas.
AB  - This study involved a comprehensive review of the histologic slides of 62
      patients who were diagnosed with uterine sarcoma from 1978 through 1988 at a
      single institution. In addition, DNA content (ploidy level) could be determined
      from the H & E slides of these tumors using image analysis. Also, 42 of these
      cases had retrievable cell blocks on which DNA analysis was performed by means of
      flow cytometry. A linear regression analysis found a high degree of correlation
      (r = 0.8) between the measurement of the DNA index of these tumors by these two
      techniques. All cases were retrospectively restaged using the newly adopted FIGO
      surgical staging criteria which found the following distribution: 22 (35.5%)
      Stage I, 10 (16.1%) Stage II, 12 (19.4%) Stage III, and 18 (29%) Stage IV. A
      multivariate analysis of 60 evaluable patients using the Cox proportional hazard
      model found that surgical staging was the most significant prognostic factor with
      respect to the endpoint of overall survival (P = 0.00004). Both patient age at
      diagnosis and mitotic index were independent from surgical staging in predicting
      outcome. Furthermore, there was a trend suggesting that DNA index also had
      prognostic value. Of particular interest was that patients with diploid tumors
      (DNA index, 0.9-1.1) had a 5-year overall survival of 72% and did not approach
      median survival; however, hyperdiploid tumors (DNA index > 1.1) and hypodiploid
      tumors (DNA index < 0.9) were associated with median survivals of 18 and 12
      months, respectively. In conclusion, this study supports the use of surgical
      staging of patients with uterine sarcomas in order to optimally determine their
      chance for survival. Further biologic investigations which may result in
      identifying those patients who could benefit from adjunctive treatment are
      recommended.

PMID- 8307503
TI  - The prognostic value of TPA and SCC in squamous cell carcinoma of the cervix.
AB  - Three hundred two patients with squamous cell carcinoma of the cervix had
      pretreatment measurement of serum levels of tissue polypeptide antigen (TPA) and
      squamous cell carcinoma antigen (SCC) to assess their prognostic value. Both
      markers were of prognostic significance in relation to stage, recurrence, and
      poor survival. The addition of TPA to SCC did not increase the percentage of
      patients with elevated pretreatment tumor marker level nor improve the prognostic
      significance. One hundred thirty-five of these patients also had serial assay of
      both markers during follow-up. Rise from normal or persistently elevated markers
      after treatment was associated with recurrence. The median lead time to
      recurrence was 2 months for SCC and 2.5 months for TPA. The addition of TPA to
      SCC in serial monitoring increased the sensitivity of detection of recurrence but
      decreased its specificity. The cost of assay of two markers over one may not
      justify the slight improvement in sensitivity of detection of recurrence. For
      squamous cell carcinoma of the cervix, SCC is a better tumor marker than TPA.

PMID- 8307504
TI  - Insertion of Groshong central venous catheters utilizing fluoroscopic techniques.
AB  - Groshong central line indwelling catheters are extensively used in gynecologic
      oncology patients for administration of chemotherapy, intravenous fluids, and
      pain medications. They are easy to maintain and have a good safety record. We
      report on the placement of these central venous catheters under direct
      fluoroscopic visualization as a method which is safe, inexpensive, and
      efficacious in high-risk patients. Fluoroscopic visualization during insertion
      provides several advantages: visualization of bony landmarks, placement of the
      guidewire into the subclavian vein and superior vena cava under direct
      visualization, and confirmation of appropriate distal placement of the Groshong
      catheter. Patient advantages include the following: (1) avoidance of unnecessary
      punctures to access the subclavian vein; (2) verification of guidewire placement
      to avoid cephalic placement; (3) passage of the guidewire only as far as the
      right atrium to avoid potential dysrrhythmias secondary to right ventricular
      irritation; and (4) a savings of approximately 60% over insertion in the general
      operating room. Thirty patients had placement under fluoroscopic visualization in
      the angiography suite of Georgetown University Hospital. The average age of the
      patients was 58 years (42-78). Sixteen patients had ovarian cancer, 6 had
      endometrial cancer, 5 had cervical cancer, and 3 had other gynecologic
      malignancies. Fifteen patients had catheters placed for chemotherapy, 14 for
      hydration, and 1 for pain control. Ten patients had had previous central venous
      catheters: 6 had been removed for infection, 2 for thrombus, 1 for completion of
      chemotherapy, and 1 for catheter kinkage. All 10 with previous catheters had
      successful placement of catheters in the angiography suite. Complications from
      insertion were minimal with one asymptomatic pneumothorax and one proximal port
      in an extravascular position. We present the technique of fluoroscopic insertion
      of Groshong catheters which is an effective method of placement in high-risk
      patients.

PMID- 8307505
TI  - Uterine leiomyosarcomas coexistent with cellular and atypical leiomyomata in a
      young woman during the treatment with luteinizing hormone-releasing hormone
      agonist.
AB  - We report a case of a 28-year-old woman who had received 2 months of intranasal
      buserelin (a luteinizing hormone-releasing hormone agonist; LH-RH agonist)
      therapy for presumed uterine leiomyomata. In addition to no reduction of the
      tumor size evaluated by sonography, heavy vaginal bleeding and abdominal pain
      recurred and worsened during the therapy. Pathological examination of the
      myomectomy and hysterectomy specimens revealed leiomyosarcomas coexistent with
      cellular, atypical, and classical leiomyomata. We suggest that this is a case of
      leiomyosarcomas arising in preexisting leiomyomata rather than de novo from the
      smooth muscle fibers of the myometrium. Furthermore, the potential of LH-RH,
      agonist therapy to delay the surgical treatment of an unsuspected leiomyosarcoma
      is high-lighted. Close monitoring of the treatment response by improvement of
      clinical symptoms and sonographic assessment of tumor size may be helpful in
      early diagnosis of an underlying malignant tumor.

PMID- 8307507
TI  - Dysgerminoma of the ovary associated with hypercalcemia.
AB  - A 19-year-old female presented with a 3-week history of abdominal swelling,
      polydipsia, and polyuria. Ultrasound examination disclosed a right adnexal mass.
      Preoperative workup showed that the serum calcium level was evaluated to 12.2
      mg/dl. Laparotomy disclosed a right ovarian tumor and a right salpingo
      oophorectomy was performed. The serum calcium level fell to within the normal
      range postoperatively. The ovarian tumor was a typical dysgerminoma on both gross
      and microscopic examination. The majority of ovarian tumors associated with
      paraneoplastic hypercalcemia in young females are small cell carcinomas of
      hypercalcemic type. It is important, however, for pathologists to be aware that
      the dysgerminoma is the second most common ovarian neoplasm associated with
      hypercalcemia in this age group, as diagnostic confusion between these two tumors
      may rarely occur on microscopic examination. The literature on ovarian tumors
      associated with hypercalcemia is briefly reviewed.

PMID- 8307506
TI  - Metastasis of breast carcinoma to a primary mucinous cystadenocarcinoma of the
      ovary.
AB  - A case of a patient with breast cancer metastatic within the tumor stroma of a
      primary ovarian carcinoma is presented. This finding is to the best of our
      knowledge the first case reported. The encountered diagnostic problems are
      discussed. A distinct peroperative frozen section diagnosis on the large, cystic,
      partially necrotic ovarian mass was not possible because of sampling problems. A
      comparable immunohistochemical staining pattern of cells being CEA negative, OC
      125 negative, and HMFG-1 positive was found in both the primary breast tumor and
      in the solid epithelial parts in the tumor stroma of the left-sided ovarian
      carcinoma, as well as in the stroma of the right ovary. Immunohistochemical
      findings in the left-sided epithelial cystic ovarian tumor showed, as expected,
      apical reactivity with antibodies directed against CEA, whereas OC-125 and HMFG-1
      were negative. Ploidy analysis showed that the primary breast carcinoma and the
      stromal part of left ovarian malignancy had the same aneuploid stemlines (DNA
      index = 1.18). The epithelial lining of the cystic ovarium carcinoma not showing
      the presence of metastatic lesion in the stroma showed the presence of a diploid
      GO,1 population only. These results show that DNA flow cytometry and
      immunohistochemistry may be helpful in assessing the origin of the malignancies
      in this unusual double presentation of both metastatic breast cancer and primary
      ovarian carcinoma.

PMID- 8307508
TI  - Primary malignant lymphoma of the uterine cervix: is radiotherapy the best
      therapeutic choice for stage IE?
AB  - The present report describes a 27-year-old woman diagnosed with Ann Arbor stage
      IE primary malignant lymphoma of the cervix. Radiation therapy was instituted as
      conventionally advocated at this early stage of the disease. Despite adequate
      local tumor response, central nervous system metastasis occurred a few months
      later. She succumbed to her condition 7 months after initial diagnosis. As occult
      distant foci may not be amenable to detection by available imaging techniques at
      the time of initial work-up, combination chemotherapy alone or in conjunction
      with radiation therapy may be the most appropriate first line of therapy in
      patients with stage IE primary malignant lymphoma of the cervix.

PMID- 8307509
TI  - Intravascular leiomyomatosis with uterine lipoleiomyoma.
AB  - A very rare case of uterine lipoleiomyomata with intravascular leiomyoma in a 48
      year-old woman is described. Located in the corpus of the uterus, the
      lipoleiomyomata showed proliferation of leiomyocytes intermingling with mature
      adipocytes. Intravascular leiomyoma was present in the broad ligament. It
      exhibited only spindle cells, and was reactive for HHF35 actin, without
      adipocytes. No continuity was detected between these tumors. Immunohistochemical
      studies revealed that the same portion of the intravascular leiomyoma was
      positive for S-100 alpha protein, NSE, factor VIII-related antigen, and HHF35
      actin. These findings suggest that the leiomyomatous tumor components arise from
      multipotent undifferentiated mesenchymal stem cells.

PMID- 8307510
TI  - Clinical stage IB endometrial adenocarcinoma with an isolated small bowel
      metastasis.
AB  - Although patients with widely disseminated endometrial adenocarcinoma can have
      tumor involving the intestine, a focal metastasis to the small bowel with no
      other evidence of extra-uterine spread has not been reported. A patient with a
      clinical stage IB, grade 2 superficially invasive endometrial adenocarcinoma was
      found to have an isolated distant metastasis to the small intestine. The patient
      has been asymptomatic and disease free for almost 4 years following postoperative
      treatment with whole abdominal radiation therapy on a Gynecologic Oncology Group
      protocol. The finding of a solitary small bowel metastasis was not predictable
      based on the current understanding of the biologic behavior of endometrial
      adenocarcinomas. This case emphasizes the need for a thorough abdominal
      exploration in patients with endometrial adenocarcinoma by surgeons trained to
      detect and resect abdominopelvic tumors, and it validates the need for innovative
      treatment protocols for women with gynecologic malignancies.

PMID- 8307511
TI  - [Ambulatory surgery--changes in surgical gynecology].

PMID- 8307512
TI  - [Problems in surgical endoscopy. Introduction].

PMID- 8307513
TI  - [Laparoscopic treatment of tubal pregnancy].

PMID- 8307514
TI  - [Laparoscopic laser therapy of endometriosis].

PMID- 8307515
TI  - [Complications of surgical laparoscopy].

PMID- 8307516
TI  - [Surgical hysteroscopy].

PMID- 8307517
TI  - [Tumorous actinomycosis of the pelvis with in situ intrauterine device].

PMID- 8307518
TI  - [Surgery and surgical monitoring by a resident. The so-called "specialist
      judgement" of the BGH 10 March 1992 (VI ZR 64/91)].

PMID- 8307519
TI  - Forensic study on stains of blood and saliva in a chimpanzee bite case.
AB  - A case of a boy bitten by a chimpanzee is reported. Forensic investigations were
      carried out on his T-shirt which had been torn open at the right armpit. By
      presumptive tests using chemical reagents and definitive tests using antisera
      against human hemoglobin A (HbAo), human serum and human saliva amylase, it was
      demonstrated that stains scattered around the torn portion of the shirt consisted
      of saliva or both blood and saliva. Though the blood was immunologically assumed
      to be human, the saliva could not be identified as human or chimpanzee. The mixed
      stains and the saliva stains were grouped A and secretor. By treatment of the
      mixed stains with a mixture of two volumes of chloroform and one volume of
      methanol (CM solution), the water-insoluble blood substance derived from blood
      was typed as O and the water-soluble substance derived from saliva was typed as A
      and secretor. The former was the victim's blood type and the latter were the
      chimpanzee saliva types.

PMID- 8307520
TI  - Differentiation between bruises and putrefactive discolorations of the skin by
      immunological analysis of glycophorin A.
AB  - In a differential study to distinguish bruises from putrefactive discoloration,
      glycophorin A, a component of the erythrocyte membrane, was extracted from
      discolored skins and detected by immunological methods utilizing an anti
      glycophorin A serum. Skin samples of 18 bruises, 8 postmortem hypostasises and 7
      putrefactive discolorations were removed from 27 bodies in which postmortem
      intervals ranged from 4 h to 2.5 months. In 13 out of the 18 bruises (72.2%),
      glycophorin A was detected by the immunological methods. It was noted that
      glycophorin A was detectable even in a severely putrefied body 10 days after
      death. In contrast, no glycophorin A was detected in any of the postmortem
      lividities or the putrefactive discolorations. These results suggest that the
      absence of glycophorin A does not always indicate a skin discoloration of
      postmortem origin, but a positive glycophorin A reaction does indicate a skin
      discoloration due to bruise.

PMID- 8307521
TI  - Death in a head-down position.
AB  - Dying in a head-down position is rare and autopsy may reveal no morphological
      findings which explain the cause of death sufficiently. Functional changes,
      mainly postural changes of circulation must be considered to explain the cause of
      death. Two cases of death are reported where death occurred in a head-down
      position, among them an autoerotic accident with suspension of a man head-down in
      a sack.

PMID- 8307522
TI  - Assessment of Lewis blood group antigens and secretor status in autopsy
      specimens.
AB  - The ability of enzyme linked immunosorbent assays (ELISA) to detect Lewis and H
      antigens in secretions obtained from 280 autopsies was assessed. The ELISA
      results were compared with those for matched blood specimens examined by
      agglutination of erythrocytes by monoclonal anti-Lewis(a) and anti-Lewis(b)
      antibodies. There was good agreement between the results for the two tests and
      the ELISAs could be used to determine secretor status of the subject. While
      determination of ABO group with monoclonal anti-A and anti-B was possible even
      with lysed blood, the results for Lewis typing by erythrocyte agglutination were
      poor if the sample was lysed or partially lysed. Detection of the antigens by
      ELISA was as efficient among elderly subjects as among younger ones and both H
      and Lewis antigens could be detected on erythrocytes and in secretions up to 127
      h after death.

PMID- 8307523
TI  - Quantified comparison of frontal sinus patterns by means of computed tomography.
AB  - The observation of frontal sinus patterning is a well-established technique of
      personal identification in forensic anthropology. Variations in size, shape,
      symmetry, border outline, and the presence and number of septa and cells are
      compared using antemortem and postmortem radiographs. Traditionally, a standard
      frontal view is utilized. Computed tomography produces contiguous radiographic
      images of the cranium at predetermined increments. Multiple comparisons of the
      sinus configuration can therefore be made at different levels. The use of
      different 'window' settings (attenuation coefficient ranges) for the production
      of CT scans is discussed. A scoring system is described for the precise and
      quantified comparison of frontal sinuses in antemortem to postmortem CT scans.
      The application of these procedures to actual cases is described.

PMID- 8307524
TI  - The study of tricyclic antidepressants in formalin-fixed human liver and formalin
      solutions.
AB  - The stability of amitriptyline, nortriptyline, desipramine and imipramine in
      formalin-fixed human liver tissue and formalin solutions was investigated. The
      levels of the tricyclic and its primary demethylated metabolite in the frozen
      liver were determined and compared with levels obtained in the formalin-fixed
      liver and formalin solutions in which the liver was stored. It was obvious that
      some methylation of the secondary amine, nortriptyline, to the corresponding
      tertiary amine, amitriptyline, and of desipramine to imipramine took place in the
      formalin environment. Nortriptyline was not detected in most cases, suggesting
      that it may degrade more rapidly than desipramine. There was no consistent ratio
      between the concentration of the drug in the frozen liver tissue versus formalin
      preserved tissue or versus formalin solution. The methylation rates of the
      secondary amines could not be quantitated. Storage of the liver tissue in
      formalin at room temperature resulted in leaching of the drugs into the formalin
      solution. The drugs tested may be detected for up to 22 months in the formalin
      fixed liver and in the formalin medium.

PMID- 8307525
TI  - Sudden death from tourniquet shock.
AB  - A fatal case of tourniquet shock is reported. The deceased, a 58-year-old tractor
      driver, died 12 h after his rescue from an overturned tractor. A 'roll-bar' on
      the tractor had pinned his left arm for approximately 24 h before his rescue.
      Histological observations revealed the typical findings of tourniquet shock.

PMID- 8307526
TI  - Determination of firing distance and firing angle by neutron activation analysis
      in a case involving gunshot wounds.
AB  - This paper reports the determination of the firing distance and a method for the
      evaluation of the firing angle in a fatal incident caused by two gunshots.
      Neutron Activation Analysis (NAA) was used to determine the Sb pattern around the
      bullet entrance holes on a garment of the victim, and around bullet holes
      produced by different shots on test targets from the gun and ammunition under
      investigation. The calibration curves obtained at various distances and firing
      angles enabled the determination of the firing distances and angles of the crime
      shots with a standard deviation of +/- 2 cm and +/- 5 degrees, respectively.

PMID- 8307527
TI  - PCP: a review of synthetic methods for forensic clandestine investigation.
AB  - A review of the synthetic routes to phencyclidine (PCP, 1-(1
      phenylcyclohexyl)piperidine) available in the open literature is presented. The
      emphasis herein is directed toward the forensic investigation of clandestine PCP
      laboratories. Six published synthetic routes to PCP/analogs are discussed. Each
      method is rated for overall yield, degree of difficulty and potential hazard, in
      order to assist the forensic chemist in evaluation of a particular clandestine
      operation. One clandestine recipe is illustrated and discussed.

PMID- 8307528
TI  - Extraction and quantitation of paraquat and diquat from blood.
AB  - Trace amounts of paraquat and diquat in blood were extracted with phenol after
      deproteinization of blood protein with a chloroform:ethanol mixture and ammonium
      sulfate. The color reaction of paraquat was achieved by addition of alkaline
      sodium dithionite to the phenolic extract. The blue paraquat radical produced was
      determined directly by measurement of the absorption of the phenol layer. The
      assay of paraquat (> or = 0.5 micrograms) in 1.0 ml of blood (recovery, 93.4%)
      could be performed within 30 min. Furthermore, simultaneous analysis of paraquat
      and diquat in the phenolic extract of the sample could be achieved by use of
      second-derivative spectroscopy within 30 min.

PMID- 8307529
TI  - Positive- and negative-ion mass spectrometry of diphenylmethane antihistaminics
      and their analogues and rapid clean-up of them from biological samples.
AB  - Positive-ion electron impact (PIEI), positive-ion chemical ionization (PICI) and
      negative-ion chemical ionization (NICI) mass spectra are presented for 15
      compounds of diphenylmethane antihistaminics and their analogues, and each
      fragmentation pathway was analyzed. In the PIEI mode, molecular peaks were very
      small or missing for most compounds. Peaks at m/z 58, due to a
      dimethylaminomethyl group liberated, constituted base peaks in five compounds.
      Peaks at m/z 165 and/or 167, due to diaromatic rings plus a methyl group,
      appeared in most compounds. In the PICI mode, peaks due to M+H and M+C2H5
      appeared in all compounds. Peaks due to diaromatic rings plus a methyl or ethyl
      group constituted base peaks in five compounds, which had an ether bond in their
      structures. In the NICI mode, anions at m/z M-H appeared in most compounds. Peaks
      at m/z 35 were observed for compounds having a chlorine group in their
      structures. Detection limits for total ion monitoring of these compounds were 20
      50 ng on column in the PIEI mode, 100-200 ng in the PICI mode and 500-1000 ng in
      the NICI mode. A rapid and simple clean-up procedure of these drugs with use of
      Sep-Pak C18 cartridges is also presented. The drugs could be detected by gas
      chromatography with DB-1 and DB-17 capillary columns with satisfactory separation
      from impurities in their underivatized forms. The recovery of the drugs, which
      had been added to whole blood and urine, was more than 60% except for meclizine.

PMID- 8307531
TI  - Alveolar macrophages and the diagnosis of drowning.
AB  - In the present study, we examined the number of alveolar macrophages in lung
      tissue from 17 cases of fresh water drowning, 22 cases of acute death and 6 cases
      of lung emphysema. When counting only the number of alveolar macrophages per
      alveolus without consideration of the alveolar size we found no relevant
      differences between the groups investigated. To exclude any influence of the
      alveolar size on the results the surface density of the alveolar macrophages and
      interstitial tissue was estimated and compared in the different groups. In cases
      of drowning, the lungs showed significantly lower values in both categories. The
      ratio of 'alveolar macrophages/interstitial tissue' was also reduced in cases of
      drowning in comparison to the other groups, however, without significant
      differences. These morphometrical results characterizing the 'emphysema aquosum'
      with almost 'empty' and dilated alveoli could be explained by a wash-out effect
      of the drowning fluid leading to a partial removal of the macrophages from the
      alveoli. This hypothesis was confirmed by the detection of alveolar macrophages
      in the drowning froth by immunohistochemical analysis. Even though alveolar
      macrophages were unambiguously identified in advanced putrefied lungs in HE
      stained sections as well as by immunohistochemical staining, an estimation of the
      number of these cells cannot provide further information for the diagnosis of
      drowning in putrefied corpses due to the autolytic destruction of the lung
      architecture providing no reliable values.

PMID- 8307530
TI  - Sudden death due presumably to internal use of methamphetamine.
AB  - A 26-year-old male was found naked and excited in the backyard of his neighbor's
      house. He was carried to a nearby hospital, and returned home with his family,
      but took a sudden turn for the worse and died. In a judicial autopsy, the ethanol
      concentration of blood was found to be 0.58 milligrams, and methamphetamine (MA)
      was detected in his blood by thin-layer chromatography. The concentration of MA
      in his blood was 4.38 mumol/dl, higher than the fatal level. The amount of MA in
      his stomach was 5.8 mg (34.58 mumol/100 g), indicating that he ingested MA by
      internal use. Among the autopsy cases of acute MA poisoning reported in Japan,
      hyperesthesia is known to last 1-3 h before death, whether the administration is
      by intravenous injection or orally. But the present case is quite unusual, as the
      death followed 6 h or more of hyperesthesia. This was attributed to the patient's
      combined intake of alcohol with MA, as it is known to decrease the mortality in
      mice.

PMID- 8307532
TI  - The investigation of beta-hydroxybutyrate as a marker for sudden death due to
      hypoglycemia in alcoholics.
AB  - The purpose of this study was to determine if the ketone body beta
      hydroxybutyrate (beta-HBA) is a useful positive marker for sudden deaths in
      chronic alcoholics, thought to be due to hypoglycemia. Beta-HBA can be reliably
      measured in postmortem samples of vitreous humour and urine. In fatalities where
      there is a history of chronic alcoholism and routine investigations, including
      autopsy and routine toxicology, yield only a fatty liver as positive findings, a
      raised level of beta-HBA can be used as an indicator for alcoholic ketosis.
      Alcoholic ketosis is often associated with antemortem hypoglycemia. Caution
      should be observed in attributing the significance of ketosis exclusively to
      alcohol in those conditions where it would otherwise be expected (i.e. diabetic
      ketoacidosis and chronic starvation). A measurement of this marker of alcoholic
      ketosis may also help in the investigation of cases where hypothermia or alcohol
      withdrawal fits are suspected.

PMID- 8307533
TI  - [What is the role of family medicine?].

PMID- 8307534
TI  - [Contact lenses--medical indications and problems].
AB  - Today, hard and soft contact lenses are useful visual aids. In common with any
      other effective medication, however, they can also produce side effects. They are
      medically indicated whenever spectacles fail to optimally compensate poor vision.
      They are not easy to customize, and wearers must be examined by the
      ophthalmologist more frequently than wearers of eye glasses. Complications are
      more common with contact lenses than with other visual aids. Nevertheless, modern
      lens systems do provide optimal correction of impaired sight in any age group.
      The present paper offers an overview of the limitations and possibilities of
      treatment with contact lenses, and discusses the medical indications.

PMID- 8307535
TI  - [Hypertension and disorders of cognitive function].
AB  - In the treatment of hypertension, the aspect of cognitive function is now
      becoming ever more important. In recent years, the influence of hypertension
      itself--as well as that of anti-hypertensive treatment--on cognitive functioning
      has repeatedly been investigated. The results obtained differ too widely to
      permit any final statement to be made on the relationships involved. The reasons
      for these differences seem to be due in particular to differences in the methods
      of investigation and random sampling involved in the studies. More recent
      studies, however, seem to support a relationship between hypertension and
      decreased cognitive performance. Improved investigations are expected to produce
      more detailed results in the future.

PMID- 8307536
TI  - [Viral safety of blood and blood products].

PMID- 8307538
TI  - [BCG immunization of newly infected HIV patients?].

PMID- 8307537
TI  - [Antiphlogistic effect of salicylic acid and its derivatives].
AB  - An overview of the literature on the effects of salicylic acid and its
      derivatives with particular consideration being given to their antiinflammatory
      properties is presented. While acetylsalicylic acid, in common with most non
      steroidal anti-inflammatory drugs, has a marked inhibitory effect on
      cyclooxygenase in vitro, salicylic acid only weakly inhibits this enzyme. Animal
      inflammation models, however, have shown that the two substances are comparable
      in terms of efficacy. It is therefore assumed that the antiinflammatory
      properties of salicylic acid and its derivatives are also based on prostaglandin
      independent mechanisms. Both salicylates and salicylic acid are used for topical
      applications. Their penetration into deeper tissue layers, as also their efficacy
      after local application have been demonstrated in both animal studies and
      clinical trials.

PMID- 8307539
TI  - [Current developments in gastrointestinal endoscopy. Part 1: The upper
      gastrointestinal tract].

PMID- 8307541
TI  - [Viral infections--clinical pictures and laboratory diagnosis. Part 4: Hepatitis
      C, D, E virus and herpesviruses].

PMID- 8307540
TI  - [Treatment strategies in infections of the shoulder joint].
AB  - Shoulder joint infections are severe pathological conditions. Since the success
      of therapy is decisively dependent on early treatment, if joint infection is
      suspected, the patient should be hospitalized immediately. Characteristic
      suspicious features are extremely severe shoulder pain, adoption of a pain
      relieving posture, and severe malaise. The diagnosis and differential diagnosis
      are discussed. In addition to selective parenteral administration of antibiotics,
      treatment comprises various methods of draining the shoulder joint in combination
      with temporary immobilization.

PMID- 8307542
TI  - [Tetrazepam in the treatment of acute cervical syndrome. Randomized double-blind
      pilot study comparing tetrazepam and placebo].
AB  - METHODS: In a double-blind study, 20 ambulatory patients with acute painful
      restriction of mobility of the cervical spine and overall marked impairment were
      treated for seven days with tetrazepam (150 mg or a lower dose from the third day
      onward) or placebo. Paracetamol was permitted in addition if required. Test
      criteria: The main criterion of efficacy was a summed score of three parameters:
      pain, restriction of mobility, and general impairment. RESULTS: The difference
      between the groups was statistically highly significant (p = 0.005). Tolerability
      was adjudged to be "very good" for the placebo group, and, on average, "good" for
      the tetrazepam group.

PMID- 8307543
TI  - [Current developments in gastrointestinal endoscopy. Part 2: Bile ducts,
      pancreas].

PMID- 8307544
TI  - [The role of the dextro-rotating cucumber borer (Deflator dextrospirillus Barks
      1957) in differential diagnosis of tick bite in the northern hemisphere].

PMID- 8307545
TI  - [Viral infections--clinical pictures and laboratory diagnosis. Part 5: Human
      immunodeficiency virus (HIV 1, HIV 2) to measles virus].

PMID- 8307546
TI  - [Topical treatment of psoriasis with calcipotriol. Report of clinical
      experience].
AB  - BACKGROUND: Numerous clinical studies have demonstrated the efficacy of
      calcipotriol, a synthetic vitamin D3 analogue, in the treatment of mild to
      moderate chronic psoriasis. METHOD: Report on clinical experience of 40 psoriasis
      patients treated with calcipotriol, alone or in combination with phototherapy.
      RESULTS: After four weeks of treatment, the condition had largely cleared up in
      eleven out of 18 patients (61%) receiving calcipotriol alone, and in 20 out of 22
      patients (91%) receiving combination treatment with UVB or UVA plus UVB. The new
      anti-psoriasis agent was well tolerated and readily accepted by the patients.
      CONCLUSION: Calcipotriol represents a valuable addition to the available therapy
      spectrum in chronic psoriasis.

PMID- 8307547
TI  - [Molecular genetics of Streptococcus mutans and the clinical application].

PMID- 8307548
TI  - [Experimental studies on the effect of heating on blood flow in the tongue of
      golden hamsters].
AB  - The effect of hyperthermia on the tongue of hamsters was evaluated histologically
      and by measuring blood flow. The dorsal tongue surface of the male mature golden
      hamster was heated at 41 degrees C-45 degrees C (surface temperature) by 2450 MHz
      microwave for 60 min, and the regional blood flow was measured using the hydrogen
      clearance method at 6, 24, 42, and 60 min during heating. When heated at 41
      degrees C (9 animals), 42 degrees C (11 animals), 43 degrees C (8 animals), 44
      degrees C (8 animals), or 45 degrees C (8 animals), the temperature of the
      measurement at 0.5 mm deep from the tongue surface was 38.4 +/- 1.0 degrees C,
      39.3 +/- 0.6 degrees C, 40.2 +/- 0.6 degrees C, 40.8 +/- 0.5 degrees C, or 43.5
      +/- 1.0 degrees C (Mean +/- S.D.), respectively. In the groups heated at 41
      degrees C, 42 degrees C, 43 degrees C, 44 degrees C, the blood flow was
      significantly increased at the first measurement (6 min) and remained elevated
      during heating. The blood flow was further increased during the second heating
      which took place after a 2 hour interval. The group heated at 45 degrees C showed
      a gradual decrease in the blood flow after the initial increase. The second
      heating induced a slight increase to a lower blood flow than the control.
      Histologically, dilation and congestion of venules, hemorrhage, interstitial
      edema in the musculature, and swelling of muscle fibers were found. Dilation,
      congestion, and rapture of capillaries beneath the mucosal epithelial layer were
      found also. These damages were more severe with an increase in heating
      temperature and duration. Additionally, thromboses were found in the group heated
      at 45 degrees C which was examined 2 hours after heating. The heated part was
      necrosed in every case heated at 45 degrees C. These results suggest that the
      critical surface temperature at which the tongue of hamsters receive irreversible
      damage lies between 44 degrees C and 45 degrees C.

PMID- 8307549
TI  - [Analysis of immune response to Japanese encephalitis virus infection in mice:
      effect of cyclosporin A on the production of HI antibody and interferon].
AB  - To study the protective factors against Japanese encephalitis (JE) virus
      infection, the effects of cyclosporin A (CsA) on the mortality, hemagglutination
      inhibition (HI) antibody response and interferon (IFN) production induced by JE
      virus were investigated in mice. CsA was given to each mouse orally 50 mg/kg/day.
      CsA had a tendency to enhance HI antibody production from 14th day and
      significantly enhanced on 21st and 28th days after inoculation with inactivated
      JE virus vaccine. Similarly CsA also enhanced HI antibody production up to at
      least 50th day after live JE virus inoculation. CsA-treated mice showed a
      significantly lower mortality rate (7/52, 13.5%) than non-CsA-treated (control)
      mice (17/51, 33.3%) (p < 0.05). CsA did not affect the serum IFN levels, which
      reached their peak values at 12 hours and fell to almost basal levels by 24 hours
      after the inoculation of inactivated JE virus vaccine. These results suggest that
      an adequate antibody response is one of the major protective factors in JE virus
      infected mice, even if it is limited in the early stage of the primary JE virus
      infection.

PMID- 8307550
TI  - [Value of transesophageal echocardiography in diagnosis of diseases of native
      heart valves].
AB  - In the clinical management of patients with valvular heart disease, transthoracic
      echocardiography (TTE) combined with Doppler has become the central diagnostic
      tool during the past decades. The development of transesophageal echocardiography
      (TEE) has led to an improved image quality especially of structures distant to
      the chest wall. However, since TEE is a semi-invasive technique, its use has to
      be considered carefully. In aortic valve disease, TEE facilitates a detailed
      study of valve morphology and allows sufficiently reliable planimetry of aortic
      valve area, at least when the multiplane approach is used. This is particularly
      helpful in those patients where Doppler interrogation from precordial windows
      fails. Aortic regurgitation is diagnosed more frequently by TEE color-flow
      imaging than by TTE; however, both techniques allow only semiquantitative
      assessment of the severity of regurgitation. TEE is also superior to TTE in
      defining the exact origin site, number and configuration of regurgitant jets in
      patients with mitral insufficiency. In particular minimal and mild mitral
      regurgitation is more easily detected by TEE than by TTE. The same is true for
      flail mitral leaflets, chordal and papillary muscle rupture, and potentially also
      for discrete forms of mitral valve prolapse. During surgery, TEE can be
      considered as an ideal tool for immediate assessment of the results of mitral
      valve reconstruction. Calculation of pressure gradients and valve area by TEE
      Doppler analysis shows comparable results to precordial studies. When multiplane
      TEE is available, Doppler beam alignment may become even improved in selected
      cases with severely excentric flow jet orientation. In addition, TEE provides of
      course clinically important information concerning presence or absence of atrial
      and particularly atrial appendage thrombi as well as of spontaneous echo contrast
      in patients with stenotic mitral valve. This is not only helpful regarding the
      decision for anticoagulation but it may also be critical in the selection of
      candidates for percutaneous mitral balloon valvuloplasty. TEE does also allow the
      morphological and functional evaluation of tricuspid and pulmonic valves. In this
      context, the use of biplane or multiplane TEE probes is superior to that of
      monoplane devices. However, currently available data does not provide unequivocal
      evidence that the analysis of tricuspid and pulmonic valve disease by TEE is
      superior to the conventional transthoracic approach.

PMID- 8307551
TI  - Value and limitations of transesophageal echocardiography in infective
      endocarditis.
AB  - Echocardiography has contributed considerably to the evolution in the management
      of patients with infective endocarditis. There is a clear hierarchy with respect
      to sensitivity of the different methods is superior when compared to 2-D and M
      mode echocardiography in identifying both vegetations and perivalvular
      complications e.g. abscess formation, aneurysms, mural endocardial lesions. For
      patients with suspected endocarditis, in whom vegetations can not be clearly
      identified or in whom abscess formation is suspected with transthoracic
      echocardiography (TTE), transesophageal echocardiography (TEE) with mono- or
      multiplane scans has become the standard diagnostic procedure. For the
      examination of prosthetic valves it is the method of choice. It has even been
      suggested that it is employed as routine measure in all patients with suspected
      infective endocarditis. TEE is a safe semi-invasive technique with an extremely
      low complication rate and high sensitivity. Its specificity depends largely on
      the patient group which is examined. In patients with indicative clinical
      symptoms the specificity and the predictive value of vegetations are high. When
      used as screening method to assess echodense formations at cardiac valves
      particularly in the elderly, in whom degenerative changes prevail, its
      specificity and positive predictive value of vegetation-like structures are much
      lower. The negative predictive value of a negative transesophageal echocardiogram
      remains high, however. Valve abscesses are detected rarely by transthoracic
      echocardiography. It is the domain of TEE to assess them particularly in the
      aortic and mitral valve area. For them the specificity and positive predictive
      value of TEE in the diagnosis of infective endocarditis is high again. Of further
      importance was the observation that patients with vegetations of > 10 mm were
      more likely to suffer embolic complications. It should be noted, however, that
      infective endocarditis remains a clinical diagnosis: neither is the demonstration
      of a vegetation already the equivalent of endocarditis, nor does missing
      vegetations completely rule out the possibility of it. But without doubt, the
      presence of vegetations, of abscess formation or a concomitant pericardial
      effusion add valuable information to clinical diagnosis of infective
      endocarditis, which still needs a "high index of suspicion".

PMID- 8307552
TI  - [Transesophageal echocardiography on the intensive care unit].
AB  - Transesophageal echocardiography is an important diagnostic tool available to the
      critical care physician. Indications for the use of transesophageal
      echocardiography in the intensive care unite include: critical illness and
      circulatory shock, thoracic aortic dissection, pulmonary embolism and
      endocarditis. Probe insertion is easy and is successful in 98% of intensive care
      patients. Further information concerning 44% of the patients was obtained with
      transesophageal as compared to transthoracic echocardiography. Transesophageal
      echocardiography is particularly helpful in evaluating cardiac size and function
      in patients with circulatory shock. When these patients are on multiple positive
      inotropic and vasopressor drugs, transesophageal echocardiography is useful in
      assessing left ventricular preload. In these patients, hemodynamic estimation of
      left ventricular filling may be misleading. More difficult is the assessment of
      hemodynamic events in patients requiring mechanical ventilation with increasing
      positive end-expiratory pressure (PEEP). This ventilation mode develops its own
      pathophysiology which superposes the effects of the underlying disease.
      Transesophageal examination of the heart after application of PEEP up to 16 cm
      H2O demonstrated an acute decrease in size of the right and left ventricle
      (Figure 1). Cardiac index was affected by the decrease in right ventricular
      dimension by external compression. The addition of positive and expiratory
      pressure to a level of 8 cm H2O did not depress cardiac index in patients with
      severe left ventricular dysfunction. PEEP ventilation is associated with abnormal
      filling patterns characterized by a significant reduction in peak early filling
      velocity, acceleration and deceleration rate of early filling and peak early to
      atrial filling velocity ratio (Figures 2a and 2b). Stoddard et al. showed, that
      these findings of transmitral Doppler flow indices are associated with abnormal
      left ventricular relaxation. Analysis of regional wall motion under different
      PEEP levels demonstrated a distinct transmission of increased intrathoracic
      pressure on the left ventricular wall. We found significant changes in systolic
      wall motion, in particular a decrease in systolic shortening of the septum and an
      increase of the lateral wall. Thus, increased intrathoracic pressure under PEEP
      ventilation is associated with nonuniform regional changes in systolic
      contraction and abnormal left ventricular relaxation. Both factors are
      responsible for the decrease in cardiac index under PEEP ventilation. Right
      ventricular infarction: The transgastric view is usefull in detecting right
      ventricular wall motion abnormalities and dilatation. Hemodynamically significant
      right ventricular infarction occurs in the posterior wall, which makes the
      transesophageal approach ideal. We studied a group of 39 patients with right
      ventricular infarction.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8307553
TI  - Intraoperative transesophageal echocardiography for detection of myocardial
      ischemia.
AB  - Preoperative myocardial ischemia seems to be a predictor of poor outcome when
      detected by electrocardiography, pulmonary capillary wedge/pressure measurement
      and echocardiography. It could be demonstrated, that regional wall motion
      abnormalities appear earlier and are more sensitive signs of myocardial ischemia
      than the ECG. Using intraoperative epicardial and transesophageal
      echocardiography, high quality 2-d echocardiographic images of the heart can be
      recorded. For monitoring of left ventricular function and wall motion the
      transesophageal approach is most often used. By the transesophageal approach the
      left ventricle can be scanned in the long axis and by the transgastric approach
      in cross sections. They correspond to the apical four-chamber and left
      parasternal cross sectional imaging of the heart. Using the transgastric approach
      in the papillary short axis view all segments representing the three coronary
      arteries can be imaged. Recording in this position have been found to be highly
      reproducible. Only localized ischemia of the apex of the ventricle may be missed.
      Methologically the rotation and translocation of the heart remain a problem using
      the cross section images of the heart. But the left ventricular papillary muscles
      and the septal-right ventricular boarders can be used as land marks. Wall motion
      is scored in five grades. In addition to the semiquantitative analysis also a
      quantitative calculation using computers is possible. Using the midd papillary
      short axis view in nearly 120 intraoperative transesophageal echocardiograms
      since 1989 analysis of the systolic wall thickening was possible in 73% of the
      patients. According to the literature review 87% of the patients undergoing
      coronary bypass surgery or non-cardiac surgery have signs of preoperative
      ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307554
TI  - [Cardiac protection in heart surgery interventions by preventive drug
      administration before extracorporeal circulation. Studies with troponin T as a
      parameter for perioperative myocardial damage].
AB  - The present study was designed to test if prophylactic intravenous nifedipine or
      nitroglycerine could reduce myocardial damage after cardiopulmonary bypass. 45
      patients scheduled for elective coronary artery bypass grafting were divided at
      random into three groups: Group 1: control; group 2: nifedipine (0.25
      microgram/kg/min); group 3: nitroglycerine (1.5 micrograms/kg/min). Infusion
      period reached from the beginning of anaesthesia until crossclamp of the aorta.
      Myocardial damage was estimated by troponin T (TnT), CK-MB and ST-segment
      analysis of the ECG. TnT is a cardiospecific protein from the contractile
      apparatus of striated muscle cells. TnT-levels might provide a very sensitive
      marker of small amounts of cardiac muscle necrosis. It was tested with an
      ELISA/one-step sandwich-assay with streptavidin-technology [9]. Criteria for
      ischemia in the ST-segment analysis were (according to Smith et al. [19]): ST
      depression > 1 mm from baseline or ST-elevation > 2 mm from baseline at J-point +
      60 ms. Statistical interpretation was done by one- and two-factorial analyses of
      variance (including multivariate analyses of variance). Correlation between two
      variables was tested by regression analysis. A level of p < 0.05 was taken for
      indicating statistical significance. Biometrical data, circulation data and data
      from cardiopulmonary bypass were without significant differences among all groups
      (Tables 1 and 2). Starting from normal values (< 0.05 ng/ml) TnT significantly
      rose in all groups immediately after cardiopulmonary bypass and remained elevated
      until the forth day after operation (values between 0.4 and 0.6 microgram/ml)
      (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307556
TI  - Genetic map of the human pseudoautosomal region reveals a high rate of
      recombination in female meiosis at the Xp telomere.
AB  - This paper describes the genetic map of the pseudoautosomal region bounded by the
      telomere of the short arms of the X and Y chromosomes. In males, meiotic exchange
      on Xp/Yp is confined to this region, leading to highly elevated recombination
      rates. The map was constructed using 11 pseudoautosomal probes (six of which are
      new) and typing individuals from 38 CEPH families. All markers have been
      physically mapped, thus providing the opportunity to compare genetic distance to
      physical distance through all intervals of the map. This comparison reveals an
      unexpected high rate of recombination in female meiosis between loci DXYS20 and
      DXYS78, within 20-80 kb from the telomere. Within this telomere-adjacent region
      no differences in male and female recombination rates are seen. Furthermore, data
      from this genetic map support the hypothesis of a linear gradient of
      recombination across most of the region in male meiosis and provide densely
      spaced anchor points for linkage studies especially in the telomeric portion of
      the pseudoautosomal region.

PMID- 8307555
TI  - Autosomal dominant polycystic kidney disease: localization of the second gene to
      chromosome 4q13-q23.
AB  - At least two loci are known to exist for autosomal dominant polycystic kidney
      disease (ADPKD). One was localized to 16p, but the second less common locus has
      remained unlinked. Over 100 microsatellite markers, distributed across all
      chromosomes, have been typed on informative family members from the large
      Sicilian kindred in which the genetic heterogeneity was first discovered. Both
      the affected and the unaffected status of every family member used in the study
      were confirmed by renal ultrasonography. This search has resulted in the
      successful localization of a second ADPKD gene to chromosome 4q. It was found to
      be flanked by the markers D4S231 and D4S414, defining a segment that spans about
      9 cM. The new locus has been designated PKD4. This second localization will allow
      researchers to target another ADPKD gene for isolation in an effort to understand
      the pathogenesis of this common disorder. Furthermore, when flanking markers for
      the second ADPKD gene are used in conjunction with flanking markers for PKD1, the
      accuracy of the diagnosis of the subtype of ADPKD present in any particular
      family will be enhanced. This will improve the accuracy of linkage-based
      presymptomatic diagnoses by reducing the error due to genetic heterogeneity.

PMID- 8307557
TI  - A somatic cell hybrid map of human chromosome 13.
AB  - We have constructed a chromosome 13 somatic cell hybrid map using seven cell
      lines: PGMEA6, a hybrid containing the entire chromosome 13, and six hybrids
      containing various deletions of chromosome 13 (BARF7, PPF22, KBF11, KSF39, CF25,
      and CF27). We have mapped 80 markers that define 10 regions of chromosome 13 with
      respect to 10 breakpoints in the mapping panel; these regions range in size from
      4 to 24 Mb, with an average size of 8 Mb. The 80 markers sublocalized on our
      mapping panel include 10 Alu-PCR clones, 6 of which were converted to sequence
      tagged sites; 40 (CA)n repeat-containing clones, 27 of which are microsatellite
      PCR markers; 8 (AAAG)n repeat-containing PCR markers, 1 two-allele PCR marker, 4
      genes or expressed sequences, and 17 anonymous DNA probes. This low-resolution
      physical map can be used as a backbone map for more refined physical mapping
      using radiation hybrids or yeast artificial chromosomes.

PMID- 8307558
TI  - Characterization of genetic defects of hemophilia A in patients of Chinese
      origin.
AB  - The molecular characterization of hemophilia A of Chinese origin was carried out
      by the polymerase chain reaction (PCR) and direct sequencing of patients' factor
      VIII genes. Single-strand conformation polymorphism (SSCP) and dideoxy
      fingerprinting (ddF) were used as screening methods to detect mutated DNAs. A
      total of 102 individuals from 87 different families, including 10 patients (10
      families) with mild-to-moderate and 92 patients (77 families) with severe
      hemophilia A, were analyzed by PCR-SSCP and PCR-ddF. Of the 87 independent cases,
      40 revealed a single mutation in the coding regions of their factor VIII genes.
      These mutations include 21 with single base changes resulting in 8 nonsense and
      13 missense codons, 16 with deletion or insertion of 1-11 nucleotides, and 3 with
      deletion of large DNA fragments. The frequency of 8 of the identified factor VIII
      polymorphisms or silent mutations was also determined among Chinese. The
      frequencies for codons 1241, 1269, and 2223 (the numbering system follows J.
      Gitschier et al., 1984, Nature 312: 326-330) were found to be different from
      those reported for other populations. As for the 47 severe cases whose mutational
      events were not readily detected by PCR-SSCP and PCR-ddF, the reverse
      transcriptase PCR method was applied. In 24 such cases analyzed, 17 were found to
      be of the "intron 22 mutations" as described by Naylor et al. (1992, The Lancet,
      342: 1066-1067), accounting for 39% of Chinese patients with hemophilia A.

PMID- 8307559
TI  - Structural organization of the human cardiac alpha-myosin heavy chain gene
      (MYH6).
AB  - The human myocardium expresses two cardiac myosin heavy chain (MyHC) isoforms,
      alpha and beta, that exist in tandem array on chromosome 14q12. We have
      previously sequenced the entire human cardiac beta-MyHC gene and now report the
      complete nucleotide sequence of the human cardiac alpha-MyHC, encompassing 26,159
      bp as well as the entire 4484-bp 5'-flanking intergenic region. The gene (MYH6)
      consists of 39 exons, 37 of which contain coding information. The 5'-untranslated
      region is split into 3 exons, with the third exon containing the AUG translation
      initiation codon. With the exception of the 13th intron of the human cardiac beta
      MyHC, which is not present within the alpha-isogene, all exon/intron boundaries
      are conserved. Conspicuous sequence motifs contained within the alpha-MyHC gene
      include four Alu repeats, a single (GT)n element, and a homopurine-homopyrimidine
      tract containing 23 GAA repeating units followed by 10 GAG repeating units.
      Comparison of the encoded amino acid sequence with a previously reported human
      alpha-MyHC cDNA sequence reveals several potential polymorphisms.

PMID- 8307560
TI  - Single-strand conformational polymorphism (SSCP) mapping of the mouse genome:
      integration of the SSCP, microsatellite, and gene maps of mouse chromosome 1.
AB  - Interspersed repetitive sequence (IRS) PCR and repetitive element-to-bubble (IRS
      bubble) PCR have been utilized to rapidly generate large numbers of mouse
      specific, chromosome 1-enriched STSs from mouse-hamster somatic cell hybrids.
      Single-strand conformational polymorphism (SSCP) has been used to localize 39 new
      repetitive element-linked STSs to the mouse map: 22 to Chr 1, 10 to Chr. 15, 2
      each to Chrs 12 and 14, and three to Chr 7. In addition, we have integrated the
      SSCP, single-strand length polymorphism, and restriction fragment length
      polymorphism maps of mouse Chr. 1, resulting in a high-density map of the
      chromosome, containing over 100 loci, all typed on a single interspecific
      backcross.

PMID- 8307561
TI  - A panel of deleted mouse X chromosome somatic cell hybrids derived from the
      embryonic stem cell line HD3 shows preferential breakage in the Hprt-DXHX254E
      region.
AB  - A panel of 91 somatic cell hybrids containing deleted mouse X chromosomes and
      falling into seven nested intervals has been isolated and characterized from
      fusions involving the murine embryonic stem cell HD3. Many of the X chromosome
      breakpoints present in these hybrids fall within regions in which few or no other
      hybrids were previously available. The apparent enrichment for breakpoints lying
      within the Hprt-DXHX254E region is discussed in relation to both the nature of
      the embryonic stem cell fusions and the presence of the Fmr1 gene associated with
      FRAXA in man within this span.

PMID- 8307562
TI  - Structural organization and evolution of the liver isoform gene for bovine
      cytochrome c oxidase subunit VIIa.
AB  - Subunit VIIa of mammalian cytochrome c oxidase is one of three nuclear-encoded
      subunits that exhibit isoforms, existing predominantly as an H-form in cardiac
      and skeletal muscle tissues and as an L-form in others. We have isolated and
      characterized the L-isoform gene (COX7aL). It is 5.4 kb long, consists of four
      exons, and is located at a CpG island. Sp1 sites and an NRF1 site are located in
      an approximately 100-bp region immediately upstream of the gene. Comparison of
      the sequence and organization with the previously described H-isoform gene shows
      identical intron-exon organizations, with the first intron of both isoform genes
      splitting the presequence coding region almost identically. These results suggest
      that the isoform genes arose by duplication from a common ancestor prior to the
      mammalian radiation and that the ancestor already contained the presequences. In
      addition, four processed pseudogenes of the L-type have been isolated and
      characterized, one of which (COX7aLP1) contains no deletions, insertions, or
      frame-shifts and can encode a precursor protein of 83 amino acids. Construction
      of a phylogenetic tree employing extant COX7aL cDNA and bovine pseudogene
      sequences suggests that the expressed bovine gene and COX7aLP1 arose from a gene
      duplication event 4.6-6.8 Mya.

PMID- 8307563
TI  - Identification and analysis of the chicken c-mil promoter: possible involvement
      of Sp1- and Ets-related proteins.
AB  - We have determined the exon organization in the 5' region of the chicken c-mil
      gene and identified its promoter. A 0.44-kb fragment containing the 5' terminus
      of the c-mil gene showed strong promoter activity when placed upstream of the
      bacterial chloramphenicol acetyltransferase gene and transfected into chicken
      embryo fibroblasts (CEF). By primer extension analysis, multiple transcriptional
      start sites were detected within the promoter region. Nucleotide sequence
      analysis revealed that the c-mil promoter had a high G + C content (71.8%) and
      contained multiple GC box-like sequences, but no TATA or CAAT boxes. Deletion
      analysis of 5' upstream sequences showed that the minimal region required for
      maximal promoter activity in CEF resides in the 99 bp located immediately
      upstream of the major initiation site. This region contains two putative Sp1
      binding sites and one PU box/PEA3 motif, defined as a recognition element for
      members of the Ets gene family. These sequences bound proteins present in nuclear
      extracts of CEF as well as in vitro synthesized Ets-related proteins, suggesting
      that the binding of Sp1 or related proteins and of Ets-related proteins within
      the promoter is important for modulation of the mil gene.

PMID- 8307564
TI  - A complete YAC contig of the Prader-Willi/Angelman chromosome region (15q11-q13)
      and refined localization of the SNRPN gene.
AB  - Since a previous report of a partial YAC contig of the Prader-Willi/Angelman
      chromosome region (15q11-q13), a complete contig spanning approximately 3.5 Mb
      has been developed. YACs were isolated from two human genomic libraries by PCR
      and hybridization screening methods. Twenty-three sequence-tagged sites (STSs)
      were mapped within the contig, a density of approximately 1 per 200 kb. Overlaps
      between YAC clones were identified by Alu-PCR dot-blot analysis and confirmed by
      STS mapping or hybridization with ends of YAC inserts. The gene encoding small
      nuclear ribonucleoprotein-associated peptide N (SNRPN), recently identified as a
      candidate gene for Prader-Willi syndrome, was localized within this contig
      between markers PW71 and TD3-21. Loci mapped within and immediately flanking the
      Prader-Willi/Angelman chromosome region contig are ordered as follows: cen-IR39
      ML34-IR4-3R-TD189-1-PW71-SNRPN -TD3-21- LS6-1-GABRB3,D15S97-GABRA5-IR10-1-CMW1+
      ++-tel. This YAC contig will be a useful resource for more detailed physical
      mapping of the region, for generation of new DNA markers, and for mapping or
      cloning candidate genes for the Prader-Willi and Angelman syndromes.

PMID- 8307565
TI  - Construction and characterization of a YAC library with a low frequency of
      chimeric clones from flow-sorted human chromosome 9.
AB  - Human chromosome 9 DNA, flow-sorted from somatic cell hybrid PK-87-9, has been
      used to construct two complete digest YAC libraries. The combined representation
      of chromosome 9 in these libraries, estimated by hybridization of chromosome 9
      specific sequences to YAC colony grids, is approximately 95%. The frequency of
      chimeric clones, analyzed by fluorescence in situ hybridization of chromosome 9
      YACs to human metaphase chromosomes, was estimated to be approximately 4%. These
      libraries provide a resource for physical mapping and for moving from genetic
      markers to disease loci on chromosome 9.

PMID- 8307566
TI  - Chromosomal localization of the mouse titin gene and its relation to "muscular
      dystrophy with myositis" and nebulin genes on chromosome 2.
AB  - In the mouse, the genes for the structural components of the myofibril titin and
      nebulin, Ttn and Neb, map to proximal Chr 2, as does the gene for a muscle
      disease, "muscular dystrophy with myositis," mdm. To facilitate the evaluation of
      Ttn and Neb as possible candidates for mdm, we have determined their relative map
      positions, using a Mus spretus/Mus musculus interspecific backcross. The gene
      order (distances in cM) cenVim-16.9 +/- 4.7-Neb-7.6 +/- 3.0-Ttn, Acra-18.0 +/-
      4.9-Pax-6-17.7 +/- 4.9-a ... has been determined. Considering the standard
      deviations, Neb, Ttn, and Acra could colocalize with mdm. Using Ttn and Neb
      probes, DNAs from mdm/mdm and mdm/+ mice were tested for restriction fragment
      variants in comparison to the M. musculus wildtype. No variants have been found
      with 11 restriction nucleases. Our data corroborate a conserved synteny
      comprising genes NEB, TTN, CHRNA1 on human Chr 2q.

PMID- 8307568
TI  - Human Zn-alpha 2-glycoprotein: complete genomic sequence, identification of a
      related pseudogene and relationship to class I major histocompatibility complex
      genes.
AB  - The human gene (AZGP1) encoding Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a
      protein present in several biological fluids and produced by a subtype of breast
      carcinomas, has been cloned and its complete nucleotide sequence determined. The
      gene spans over 9.7 kb, and its overall organization and nucleotide sequence are
      very similar to those of the first four exons of class I MHC genes. However, the
      Zn-alpha 2-gp gene differs from these genes in several significant ways. It lacks
      the coding information for the transmembrane and cytoplasmic domains typical of
      MHC genes, which is consistent with its presence as a soluble protein in
      different physiological and pathological fluids. In addition, it contains a high
      density of repetitive sequences, including Alu, MER, and MIR elements, which are
      not present at equivalent positions in class I MHC genes. Finally, its 5'
      flanking region lacks the class I MHC regulatory complex and the interferon
      consensus sequence characteristic of class I MHC genes. These findings may
      explain the different expression pattern of Zn-alpha 2-gp and class I MHC genes
      in human tissues. Southern blot hybridization of DNA from several species with a
      cDNA probe indicated that Zn-alpha 2-gp genes are present in a wide variety of
      animal species, including monkey, rat, mouse, dog, cow, and rabbit. The human
      genome also contains a putative Zn-alpha 2-gp pseudogene that has been isolated
      and partially characterized. This pseudogene has an intron-exon organization
      identical to that of the functional gene, but it presents two deleterious
      mutations in the third exon that lead to the appearance of premature stop codons.
      Finally, considering the lack of polymorphism in the Zn-alpha 2-gp gene in
      comparison with MHC genes, putative roles for this human glycoprotein in the
      transport of nonpolymorphic substances or in intercellular recognition processes
      are proposed.

PMID- 8307567
TI  - Isolation of the cDNA and chromosomal localization of the gene (TAX1) encoding
      the human axonal glycoprotein TAG-1.
AB  - The transient axonal glycoprotein (TAG-1) is a cell adhesion molecule that
      promotes neurite outgrowth and belongs to the immunoglobulin superfamily. We have
      isolated cDNAs encoding TAX1, the human homologue of TAG-1. Human TAX1 shows a
      high degree of homology to rat TAX1 and less to its chick counterpart, axonin-1,
      with 91 and 75% identity at the amino acid level, respectively. The numbers of
      immunoglobulin (IgC2) domains and fibronectin repeats present in TAG-1 are
      conserved among the three species. The highest degree of conservation occurs in
      the second IgC2 domain (98% with the rat and 82% with the chick). The human
      homologue also contains a putative N-terminal signal sequence and a C-terminal
      hydrophobic sequence, suggestive of linkage to the cell membrane via
      phosphatidylinositol. In addition, the two mammalian TAG-1 proteins share the RGD
      tripeptide, a motif known to mediate recognition of fibronectin by integrins. In
      situ hybridization to human metaphase chromosomes maps the TAX1 gene encoding
      human TAG-1 to a single location on chromosome 1q32.

PMID- 8307569
TI  - A genetic map of index DNA loci on bovine chromosome 21.
AB  - Genetic maps of highly polymorphic index DNA loci exist essentially only in
      humans and some experimental organisms. Here we report the first genetic map of
      highly polymorphic index DNA loci in livestock for bovine chromosome 21. This map
      consists of six loci with an average heterozygosity of 82%, each with a minimum
      of five alleles, spaced at an average genetic distance of 9.7 cM, and covers most
      of the expected length of the acrocentric bovine chromosome 21. The order of
      markers along the chromosome is cen-ETH 131-UWCA 4-TGLA 337-TGLA 122-CSSM 18-GMBT
      16-tel. There is heterogeneity among the recombination fractions between the
      sexes.

PMID- 8307570
TI  - Genomic structure of the EWS gene and its relationship to EWSR1, a site of tumor
      associated chromosome translocation.
AB  - The EWS gene has been identified based on its location at the chromosome 22
      breakpoint of the t(11;22)(q24;q12) translocation that characterizes Ewing
      sarcoma and related neuroectodermal tumors. The EWS gene spans about 40 kb of DNA
      and is encoded by 17 exons. The nucleotide sequence of the exons is identical to
      that of the previously described cDNA. The first 7 exons encode the N-terminal
      domain of EWS, which consists of a repeated degenerated polypeptide of 7 to 12
      residues rich in tyrosine, serine, threonine, glycine, and glutamine. Exons 11,
      12, and 13 encode the putative RNA binding domain. The three glycine- and
      arginine-rich motifs of the gene are mainly encoded by exons 8-9, 14, and 16. The
      DNA sequence in the 5' region of the gene has features of a CpG-rich island and
      lacks canonical promoter elements, such as TATA and CCAAT consensus sequences.
      Positions of the chromosome 22 breakpoints were determined for 19 Ewing tumors.
      They were localized in introns 7 or 8 in 18 cases and in intron 10 in 1 case.

PMID- 8307571
TI  - Primary sequence, evolution, and repetitive elements of the Gallus gallus
      (chicken) beta-globin cluster.
AB  - The DNA sequence of the Gallus gallus (chicken) beta-globin cluster was completed
      and analyzed. This G + C-rich region is 23.7 kb in length and includes the rho-,
      beta H-, beta A-, and epsilon-globin genes, the enhancer found between the beta A
      and epsilon genes, and three upstream DNase I hypersensitive sites. The CpG
      dinucleotides are nonrandomly distributed, being present at an increased relative
      frequency near the promoters and upstream hypersensitive sites. The cluster has
      an unusually low TA dinucleotide frequency. The upstream hypersensitive sites
      (5'HS1, 5'HS2, and 5'HS3) contain DNA sequence motifs recognized by erythroid
      transcription factors. However, no significant sequence similarity was found
      among the upstream hypersensitive sites and the beta A/epsilon enhancer. The G.
      gallus upstream site sequences were not similar to the upstream sites of the
      mammalian globin clusters, probably due to the small size of the functional
      regions and large evolutionary distance between the classes. The avian cluster
      evolved by gene duplication from an ancestor beta-globin gene, first producing
      the epsilon and the rho/beta H/beta A ancestor genes, then the rho and the beta
      H/beta A ancestor genes, and finally the beta H- and beta A-globins. Four
      probable gene conversions can be documented: beta A to beta H, epsilon to beta H,
      and rho/epsilon (twice). The cluster shows a massive overrepresentation of a non
      LTR retrotransposon, CR1, which accounts for 16% of the DNA. We suggest that the
      locus is a preferred site for CR1 insertion.

PMID- 8307572
TI  - Mapping and cloning of the critical region for the spinocerebellar ataxia type 1
      gene (SCA1) in a yeast artificial chromosome contig spanning 1.2 Mb.
AB  - The gene responsible for spinocerebellar ataxia type 1 (SCA1) has been localized
      to a 6.7-cM region between the centromeric marker D6S109 and the telomeric marker
      D6S89. We screened two yeast artificial chromosome (YAC) libraries using sequence
      tagged sites at D6S89 and at newly identified markers in 6p22-p23. Fifty YAC
      clones were identified and 34 insert termini were isolated from some of these
      YACs for detailed overlap mapping and long-range restriction analysis. A large
      YAC contig estimated to span 2.5 Mb was developed and genetic analysis in five
      large SCA1 kindreds using highly informative dinucleotide repeat polymorphisms
      mapped to this contig allowed the identification of D6S274 as the closest
      centromeric flanking marker for SCA1. Long-range restriction analysis determined
      the size for the critical SCA1 region, as defined by the two flanking markers
      D6S274 and D6S89, to be 1.2 Mb. This region is spanned by a minimum set of four
      nonchimeric YAC clones. The development of a 2.5-Mb YAC contig in 6p22-p23
      provides valuable reagents for characterization of this genomic region and for
      the cloning of the SCA1 gene.

PMID- 8307573
TI  - A eutherian X-linked gene, PDHA1, is autosomal in marsupials: a model for the
      evolution of a second, testis-specific variant in eutherian mammals.
AB  - We report the cloning and mapping of a gene (PDHA) for the pyruvate dehydrogenase
      E1 alpha subunit in marsupials. In situ hybridization and Southern blot analysis
      show that PDHA is autosomal in marsupials, mapping to chromosome 3q in
      Sminthopsis macroura and 5p in Macropus eugenii. Since these locations represent
      a region that was translocated to the p arm of the human X chromosome following
      marsupial/eutherian divergence, we suggest that the marsupial PDHA gene is
      homologous to PDHA1, the somatic eutherian isoform located on human Xp and mouse
      X. Only one copy of PDHA is found in marsupials, whereas a second, testis
      specific, intronless form is observed in eutherian mammals. We also suggest that
      translocation of PDHA to the eutherian X chromosome, which is inactivated during
      spermatogenesis, led to the evolution of a second testis-specific locus by
      retroposition to an autosome.

PMID- 8307574
TI  - The human peripheral benzodiazepine receptor gene: cloning and characterization
      of alternative splicing in normal tissues and in a patient with congenital lipoid
      adrenal hyperplasia.
AB  - The mitochondrial benzodiazepine receptor (mBzR) appears to be a key factor in
      the flow of cholesterol into mitochondria to permit the initiation of steroid
      hormone synthesis. The mBzR consists of three components; the 18-kDa component on
      the outer mitochondrial membrane appears to contain the benzodiazepine binding
      site, and is hence often termed the peripheral benzodiazepine receptor (PBR).
      Using a cloned human PBR cDNA as probe, we have cloned the human PBR gene. The 13
      kb gene is divided into four exons, with exon 1 encoding only a short 5'
      untranslated segment. The 5' flanking DNA lacks TATA and CAAT boxes but contains
      a cluster of SP-1 binding sites, typical of "house-keeping" genes. The encoded
      PBR mRNA is alternately spliced into two forms: "authentic" PBR mRNA retains all
      four exons, while a short form termed PBR-S lacks exon 2. While PBR-S contains a
      102-codon open reading frame with a typical initiator sequence, the reading frame
      differs from that of PBR, so that the encoded protein is unrelated to PBR. RT-PCR
      and RNase protection experiments confirm that both PBR and PBR-S are expressed in
      all tissues examined and that expression PBR-S is about 10 times the level of
      PBR. Expression of PBR cDNA in pCMV5 vectors transfected into COS-1 cells
      resulted in increased binding of [3H]PK11195, but expression of PBR-S did not. It
      has been speculated that patients with congenital lipoid adrenal hyperplasia, who
      cannot make any steroids, might have a genetic lesion in mBzR. RT-PCR analysis of
      testicular RNA from such a patient, sequencing of the cDNA, and blotting analysis
      of genomic DNA all indicate that the gene and mRNA for the PBR component of mBzR
      are normal in this disease.

PMID- 8307575
TI  - Genomic structure of and a cardiac promoter for the mouse carnitine
      palmitoyltransferase II gene.
AB  - The mouse carnitine palmitoyltransferase II gene has been isolated and its
      genomic structure determined. The gene contained five exons, including an
      unusually long 1305-nt exon 4. The exon/intron boundaries were sequenced and
      conformed to the consensus splice junction sequences. The transcription start
      site was determined from adult mouse heart mRNA by primer extension analysis and
      confirmed by 5' rapid amplification of cDNA ends. A promoter that differs from
      the previously published promoter for the carnitine palmitoyltransferase II gene
      was isolated and sequenced. When placed in a mammalian expression vector, this
      promoter was shown to drive the chloramphenicol acetyltransferase gene in mouse
      hepatoma cells. This new promoter is the major driver of carnitine
      palmitoyltransferase II gene expression in heart and may also be active in liver.

PMID- 8307576
TI  - Genetic linkage of mild pseudoachondroplasia (PSACH) to markers in the
      pericentromeric region of chromosome 19.
AB  - Pseudoachondroplasia (PSACH) is a dominantly inherited form of short-limb
      dwarfism characterized by dysplastic changes in the spine, epiphyses, and
      metaphyses and early onset osteoarthropathy. Chondrocytes from affected
      individuals accumulate an unusual appearing material in the rough endoplasmic
      reticulum, which has led to the hypothesis that a structural abnormality in a
      cartilage-specific protein produces the phenotype. We recently identified a large
      family with a mild form of pseudoachondroplasia. By genetic linkage to a
      dinucleotide repeat polymorphic marker (D19S199), we have localized the disease
      gene to chromosome 19 (maximum lod score of 7.09 at a recombination fraction of
      0.03). Analysis of additional markers and recombinants between the linked markers
      and the phenotype suggests that the disease gene resides within a 6.3-cM interval
      in the immediate pericentromeric region of the chromosome.

PMID- 8307577
TI  - Linkage of typical pseudoachondroplasia to chromosome 19.
AB  - Pseudoachondroplasia (PSACH) is an autosomal dominant dwarfing condition
      associated with disproportionate short stature, marked joint deformities, and
      early onset osteoarthritis. Previous linkage studies have excluded linkage to
      cartilage and noncartilagenous extracellular matrix candidate genes. Here, we
      report mapping the pseudoachondroplasia gene to chromosome 19. Maximum lod scores
      of 4.70, 4.15, and 4.86 at theta = 0.00 were found for D19S212, D19S215, and
      D19S49, respectively. Multipoint analysis suggests the following order: D19S253
      D19S199-(D19S212/PSACH/D19S215)-++ +D19S222-D19S49.

PMID- 8307578
TI  - Fibrillin genes map to regions of conserved mouse/human synteny on mouse
      chromosomes 2 and 18.
AB  - Fibrillin proteins are major structural components of the 10-nm microfibrils
      found in elastic and nonelastic connective tissues. Previous studies have mapped
      the human genes for two fibrillins to chromosome bands 15q21 (FBN1) and 5q23-q31
      (FBN2) and have demonstrated that FBN1 mutations are associated with Marfan
      syndrome, while FBN2 is linked to the gene for congenital contractural
      arachnodactyly. Here, we report the isolation of genomic clones of the
      corresponding mouse fibrillin genes (Fbn-1 and Fbn-2). By analyzing a mapping
      panel of mouse x rodent somatic hybrid cell lines, we have assigned the Fbn-1
      gene to mouse chromosome 2 and the Fbn-2 gene to mouse chromosome 18. We then
      sublocalized the fibrillin genes to bands 2F (Fbn-1) and 18D-E1 (Fbn-2) by
      fluorescence in situ hybridization. These regions are known to exhibit conserved
      synteny with the regions on human chromosomes 15 and 5 that carry the homologous
      human fibrillin genes. In addition, the Fbn-1 gene maps in the vicinity of the
      gene for a connective tissue disorder on mouse chromosome 2 called Tight-skin
      (Tsk).

PMID- 8307579
TI  - Structure and organization of the human alpha class glutathione S-transferase
      genes and related pseudogenes.
AB  - We have isolated and characterized genomic DNA encoding several human Alpha class
      glutathione S-transferase genes and pseudogenes. All the genes are composed of
      seven exons with boundaries identical to those of the Alpha class genes in rats.
      The GSTA1 gene is approximately 12 kb in length and is closely flanked by other
      Alpha class gene sequences. The complete sequence of the 1.7-kb intergenic region
      between exon 7 of an upstream pseudogene and exon 1 of the GSTA1 gene has been
      determined. An additional gene that encodes an uncharacterized Alpha class
      glutathione S-transferase has been identified. The protein derived from this gene
      would have 19 amino acid substitutions compared with the GSTA1 isoenzyme. Several
      pseudogenes with single-base and/or complete exon deletions have been identified,
      but no reverse-transcribed pseudogenes have been detected. The occurrence of
      multiple genes and pseudogenes on a single fragment of cloned genomic DNA and the
      prior identification of a single chromosomal region (6p12) of hybridization
      (Board and Webb, 1987, Proc. Natl. Acad. Sci. USA 84:2377-2381) suggest that all
      the Alpha class genes are members of a closely linked gene family that has
      evolved by duplication and gene conversion events.

PMID- 8307580
TI  - The gene for murine CTP:phosphocholine cytidylyltransferase (Ctpct) is located on
      mouse chromosome 16.
AB  - CTP:phosphocholine cytidylyltransferase is the rate-controlling enzyme in
      phosphatidylcholine biosynthesis and is essential for the survival of eukaryotic
      cells. The murine cDNA for the cytidylyltransferase was cloned and sequenced. A
      genomic clone was isolated and the chromosomal location of the Ctpct locus
      determined by Southern blot hybridization of DNAs from a panel of interspecific
      backcross progeny derived from matings of [(C57BL/6J x Mus spretus)F1 x C57BL/6J]
      mice. These data place the Ctpct gene on mouse chromosome 16 between the Smst and
      Stf-1 genes.

PMID- 8307581
TI  - Regional mapping of short tandem repeats on human chromosome 10: cytochrome P450
      gene CYP2E, D10S196, D10S220, and D10S225.
AB  - Human CYP2E encodes an ethanol-inducible cytochrome P450 monooxygenase that
      metabolizes various carcinogens and may therefore play a role in cancer
      susceptibility. An intronic (GGAT)n.(CCTA)n repeat element was found to display
      limited polymorphism in Caucasoids and was used as a sequence-tagged site for
      genomic amplification from somatic cell hybrids to localize CYP2E to 10q24.3
      qter; using the same panel, three microsatellite markers, D10S196, D10S220, and
      D10S225, were mapped to 10q21. The close synteny of CYP2E, CYP2C, and CYP17
      belonging to two different cytochrome P450 families suggests a central role for
      the long arm of chromosome 10 in the evolution of this large gene superfamily.

PMID- 8307582
TI  - A transducin-like gene maps to the autosomal dominant polycystic kidney disease
      gene region.
AB  - A novel human gene (sazD) that maps to the autosomal dominant polycystic kidney
      disease region shares sequence similarity with members of the beta-transducin
      superfamily. The cDNA sazD-c predicts an approximately 58-kDa protein (sazD) with
      seven internal repeats, similar to the WD-40 motif of the transducin family. The
      size of this protein family has been expanding rapidly; however, neither the
      structure nor the function of this repeated motif is known. Preliminary data do
      not suggest that sazD is mutated in patients with polycystic kidney disease.

PMID- 8307583
TI  - Isolation and genetic mapping of four microsatellite repeats from chromosome 3p21
      using 40 CEPH pedigrees.
AB  - We have isolated and characterized the microsatellite markers D3S1447, D3S1448,
      D3S1449, and D3S1450, with PIC values of 0.771, 0.644, 0.633, and 0.552,
      respectively, from a hamster/human chromosome 3 library. By typing 40 CEPH
      pedigrees with each of these novel markers, we have sublocalized each
      microsatellite to 3p21 and with multipoint analyses have shown that the
      likelihood of the order centromere-D3S13-24.24 cM-D3S1450-9.41 cM-D3S1447-7.05 cM
      D3F15S2-3 cM-[D3S1448-2.2 cM-D3S1449]-6.13 cM-D3S1100- telomere significantly
      exceeds any other order (8.0 x 10(3):1). These finely mapped markers will be
      extremely useful in aiding in the physical characterization of 3p21, which has
      been implicated in a range of tumor tissues.

PMID- 8307584
TI  - Regional mapping of a human rod alpha-transducin (GNAT1) gene to chromosome 3p22.

PMID- 8307585
TI  - The human CD53 gene, coding for a four transmembrane domain protein, maps to
      chromosomal region 1p13.

PMID- 8307587
TI  - An oligonucleotide probe specific to the centromeric region of human chromosome
      5.

PMID- 8307586
TI  - The CA repeat marker D17S791 is located within 40 kb of the WNT3 gene on
      chromosome 17q.

PMID- 8307588
TI  - Localization of the human growth arrest-specific gene (GAS1) to chromosome bands
      9q21.3-q22, a region frequently deleted in myeloid malignancies.

PMID- 8307589
TI  - A homologue of the Drosophila Son of sevenless gene maps to mouse chromosome 17.

PMID- 8307590
TI  - Report of the Fourth International Workshop on Human Chromosome 21.

PMID- 8307591
TI  - Multiresolution wavelet analysis of evoked potentials.
AB  - Neurological injury, such as from cerebral hypoxia, appears to cause complex
      changes in the shape of evoked potential (EP) signals. To characterize such
      changes we analyze EP signals with the aid of scaling functions called wavelets.
      In particular, we consider multiresolution wavelets that are a family of
      orthonormal functions. In the time domain, the multiresolution wavelets analyze
      EP signals at coarse or successively greater levels of temporal detail. In the
      frequency domain, the multiresolution wavelets resolve the EP signal into
      independent spectral bands. In an experimental demonstration of the method,
      somatosensory EP signals recorded during cerebral hypoxia in anesthetized cats
      are analyzed. Results obtained by multiresolution wavelet analysis are compared
      with conventional time-domain analysis and Fourier series expansions of the same
      signals. Multiresolution wavelet analysis appears to be a different, sensitive
      way to analyze EP signal features and to follow the EP signal trends in
      neurologic injury. Two characteristics appear to be of diagnostic value: the
      detail component of the MRW displays an early and a more rapid decline in
      response to hypoxic injury while the coarse component displays an earlier
      recovery upon reoxygenation.

PMID- 8307592
TI  - ECG data compression with time-warped polynomials.
AB  - This paper presents a new adaptive compression method for ECG's. The method
      represents each R-R interval by an optimally time-warped polynomial. It achieves
      a high-quality approximation at less than 250 bits/s. The article shows that the
      corresponding rates for other transform based schemes (the DCT and the DLT) are
      always higher. Also, the new method is less sensitive to errors in QRS detection
      and it removes more (white) noise from the signal. The reconstruction errors are
      distributed more uniformly in the new scheme and the peak error is usually lower.
      The reconstruction method is also useful for adaptive filtering of noisy ECG
      signals.

PMID- 8307593
TI  - Cross-correlation analyses of nonlinear systems with spatiotemporal inputs.
AB  - Methods are presented for analyzing the low-order stimulus-response cross
      correlation functions (or kernels) of visual neurons studied with spatiotemporal
      white noise. In particular, formulas are derived that relate the low-order
      kernels of a cell to its responses to single-drifting, double-drifting, and
      counterphase gratings. The harmonic response terms contributed by the low-order
      kernels include a mean response term, first- and second-harmonic terms, and sum-
      and difference-harmonic terms. Using the formulas in this paper, one can obtain
      kernel-based predictions for the spatiotemporal-frequency tuning of each
      harmonic. These kernel-based predictions can then be compared with harmonic
      tuning data obtained in experiments with real grating stimuli. The methods are
      illustrated using data recorded from one simple and one complex cell from the
      primary visual cortex of the monkey. The approach of transforming low-order
      kernels into predicted harmonic tuning functions provides a useful data reduction
      technique as well as providing insight into the interpretation of kernels.

PMID- 8307594
TI  - Peptides secondary structure prediction with neural networks: a criterion for
      building appropriate learning sets.
AB  - Artificial neural networks have been recently applied with success for protein
      secondary structure prediction. So far, one of the two main aspects on which
      neural net performance depends, the topology of the net, has been considered. The
      present work addresses the other main aspect, the building up of the learning
      set. We present a criterion to build up suitable learning sets based on the alpha
      helix percentage. Starting from a set of several well known proteins, we formed 7
      groups of proteins with similar helix percentages and we used them for the
      learning of the same neural net. We found that the best secondary structure
      prediction for each of the tested proteins (not belonging to the initial set) was
      the one obtained using the learning set whose helix percentage was closest to
      that of the tested protein. The accuracy of correct prediction of our method on
      three types of secondary structure (alpha-helix, beta-sheet and coil), has been
      compared with the accuracy of other secondary structure prediction methods.

PMID- 8307595
TI  - Measurement of acetylcholine receptor function in microcircuit-coupled myoblasts.
AB  - An electrophysiological measurement principle for long-term, noninvasive
      monitoring of the nicotinic acetylcholine receptor (nAChR) function is described.
      The measurement is based on the ability to record agonist-induced depolarizations
      of clonal myoblasts that have formed high impedance seals with extracellular
      microcircuit electrodes. The technique appears promising for several types of
      assays and environmental monitoring applications.

PMID- 8307596
TI  - An optical fiber transducer for single myofibril force measurement.
AB  - A force transducer has been developed for use in force measurement of skeletal
      muscle myofibrils. The transducer is suitable for measurement of passive and
      contractile forces in a range up to 200 micrograms, with 1 microgram resolution.
      It is based upon the operating principle of the deflection of an optical fiber of
      known compliance, sensed by the differential illumination of two
      phototransistors. Attractive features include ease of operation and specimen
      mounting, high bandwidth, adaptability for different force ranges, and simple and
      inexpensive construction.

PMID- 8307597
TI  - A robust controller for insulin pumps based on H-infinity theory.
AB  - The feedback control of insulin pumps for diabetic patients is discussed. Because
      the parameters in the mathematical model of the blood glucose dynamics present a
      considerable amount of uncertainty, the H-infinity framework is well suited for
      the design of controllers that take into account a nice compromise between robust
      closed-loop regulation of a constant set point and performance expressed in terms
      of peak values of the plasma glucose concentration.

PMID- 8307598
TI  - The four-electrode resistivity technique in anisotropic media: theoretical
      analysis and application on myocardial tissue in vivo.
AB  - Several aspects of the four-electrode resistivity technique were studied with
      special emphasis on the theoretical determination of penetration depth and sample
      volume in anisotropic media such as (cardiac) muscle. Moreover, the presence of a
      thin disturbing layer on top of the medium under study was analyzed. A four
      electrode sensor was developed for the measurement of local myocardial
      resistivity in two orthogonal directions. The sensor was applied to the
      epicardium of anesthetized open chest dogs and, as an example, results are given
      on the frequency dependence (5-60 kHz) and the changes during the cardiac cycle
      of longitudinal and transverse myocardial resistivity.

PMID- 8307599
TI  - Modeling of neural systems by use of neuronal modes.
AB  - A methodology for modeling spike-output neural systems from input-output data is
      proposed, which makes use of "neuronal modes" (NM) and "multi-input threshold"
      (MT) operators. The modeling concept of NM's was introduced in a previously
      published paper in order to provide concise and general mathematical
      representations of the nonlinear dynamics involved in signal transformation and
      coding by a class of neural systems. This paper presents and demonstrates (with
      computer simulations) a method by which the NM's are determined using the 1st-
      and 2nd-order kernel estimates of the system, obtained from input-output data.
      The MT operator (i.e., a binary operator with multiple real-valued operands which
      are the outputs of the NM's) possesses an intrinsic refractory mechanism and
      generates the sequence of output spikes. The spike-generating characteristics of
      the MT operator are determined by the "trigger regions" defined on the basis of
      data. This approach is offered as a reasonable compromise between modeling
      complexity and prediction accuracy, which may provide a common methodological
      framework for modeling a certain class of neural systems.

PMID- 8307600
TI  - Quantitative colorimetric analysis of liquid crystal films (LCF) for phantom
      dosimetry in microwave hyperthermia.
AB  - A fully quantitative analysis of liquid crystal film (LCF) color patterns, in
      phantom thermal dosimetry for microwave hyperthermia, is presented. An accurate
      determination of absorption rate density (ARD) is achieved by color image
      computer processing. This work is proven to be an improvement upon the semi
      quantitative or qualitative descriptions of LCF colors performed essentially by
      visual analysis of photographs. Temperature-induced chromatic distributions are
      acquired as R, G, B (red, green, blue) signals by a CCD camera connected to a PC
      frame grabber board. These data, stored into three 512 x 512 memory buffers, are
      then converted to H, S, I (hue, saturation, intensity) colorimetric system.
      Provided a suitable calibration of the LCF, the H quantity can be transformed to
      temperature using a monotonic relationship. In this way, a temperature accuracy
      lower than 0.2 degrees C and a spatial resolution less than 1 mm are obtained. A
      sequence of thermal maps can be acquired and stored on disk at a maximum rate of
      1 image/2 s, and then the ARD is calculated at each pixel of the map using the
      least squares method.

PMID- 8307601
TI  - A fast method to compute the potential in the multisphere model.
AB  - A series expansion is derived for the potential distribution, caused by a dipole
      source in a multilayered sphere with piecewise constant conductivity. When the
      radial coordinate of the source approaches the radial coordinate of the field
      point the spherical harmonics expansion converges only very slowly. It is shown
      how the convergence can be improved by first calculating an asymptotic
      approximation of the potential and using the so-called addition-subtraction
      method. Since the asymptotic solution is an approximation of the true solution,
      it gives some insight on the dependence of the potential on the conductivities.
      The formulas will be given in Cartesian coordinates, so that difficulties with
      coordinate transformations are avoided. Attention will be paid to the (fast)
      computation of the partial derivatives of the potential, which is useful for
      inverse algorithms.

PMID- 8307602
TI  - Effects of induced electric fields on finite neuronal structures: a simulation
      study.
AB  - In this paper we present an analysis of magnetic stimulation of finite length
      neuronal structures using computer simulations. Models of finite neuronal
      structures in the presence of extrinsically applied electric fields indicate that
      excitation can be characterized by two driving functions: one due to field
      gradients and the other due to fields at the boundaries of neuronal structures.
      It is found that boundary field driving functions play an important role in
      governing excitation characteristics during magnetic stimulation. Simulations
      indicate that axons whose lengths are short compared to the spatial extent of the
      induced field are easier to excite than longer axons of the same diameter.
      Simulations also indicate that independent cellular dendritic processes are
      probably not excited during magnetic stimulation. Analysis of the temporal
      distribution of induced fields indicates that the temporal shape of the stimulus
      waveform modulates excitation thresholds and propagation of action potentials.

PMID- 8307603
TI  - Induction of tolerance by T-cell vaccination is possible beyond the area of
      autoimmunity: down-regulation of immunity directed to foreign protein antigens.
AB  - T-cell vaccination using antigen-specific lines or clones has been shown to be
      effective in down-regulating immunity in various experimental autoimmune models.
      Anti-idiotypic networks developing during differentiation of the immune system
      are considered to be a safeguard against autoimmunity and these pre-existing
      networks are supposed to be a prerequisite for successful vaccination. However,
      the interesting question of feasibility of T-cell vaccination beyond the area of
      autoimmunity remains to be answered. The present study is the first one providing
      evidence of successful T-cell vaccination in mice immunized against foreign
      protein antigens (in this system supposedly no pre-existing network exists).
      Intraperitoneal (i.p.) administration of hen egg lysozyme (HEL)- and chicken egg
      albumin (OVA)-specific lymph node cells (LNC) were shown to effectively down
      regulate immunity (as measured in a delayed type of hypersensitivity) to HEL and
      OVA, respectively. In contrast, vaccination was unsuccessful with methylated
      bovine serum albumin (mBSA)-specific LNC in mBSA immunity. Suppression induced by
      HEL- and OVA-specific LNC was antigen specific. Unlike the greater part of other
      studies, in which antigen-specific lines or clones were used, we used draining
      LNC of immunized mice, which after activation were fixed with glutardialdehyde
      and injected i.p. 10 days before immunization. Finally, effects of T-cell
      vaccination were studied in a chronic HEL-induced arthritis. Joint swelling, cell
      influx and cartilage matrix depletion were significantly less in mice treated
      with antigen-specific cells. We conclude that successful vaccination is feasible
      in mice rendered immune to foreign protein antigens using a pool of LNC as source
      of vaccine, suggesting no necessity of a strong pre-existing network.

PMID- 8307604
TI  - Lack of connectivity between the induced and autoimmune repertoires of lpr/lpr
      mice.
AB  - It has been proposed that the autoantibody-secreting cells active during
      autoimmune diseases are derived from B cells initially responding to
      environmental antigens. In order to test the relationship between the antigen
      induced and autoimmune repertoires, we monitored the fate of antigen-activated
      idiotypically defined B cells present in mice that developed the systemic lupus
      erythematosus (SLE)-like syndrome associated with the lpr mutation. Mice
      homozygous for both the A/J-derived Igh and Ig kappa region haplotypes and the
      lpr mutation were bred. Immunization of these mice with p-azophenylarsonate (Ars)
      protein conjugates elicited the idiotypic components (IdCR) characteristic of the
      A/J anti-Ars response and did not interfere with the spontaneous development of
      the lpr-mediated autoimmune disease. These Id/lpr mice provided an ideal system
      for studying the relationship between the exogenously and endogenously induced
      responses because: (1) VHIdCR antibodies have been shown to bind autoantigens in
      vitro; and (2) serological and molecular reagents exist which can identify and
      monitor VHIdCR antibody production as disease progresses. Serum samples and
      hybridoma cell lines derived from non-immune as well as Ars-keyhole limpet
      haemocyanin (KLH)-immunized Id/lpr mice were monitored for idiotype expression as
      well as Ars and ssDNA reactivity at various stages of disease progression. We
      found that antibodies utilizing the VHIdCR gene segment did not preferentially
      contribute to the autoantibody pool. Moreover, even when IdCR B-cell clones were
      expanded by deliberate immunization with Ars-KLH, Ars non-binding variants were
      only rarely detected among the activated B-cell populations of diseased mice.
      These results indicate that there is only minimal overlap between the VHIdCR
      conventional and autoimmune repertoires.

PMID- 8307606
TI  - Studies of lymphocyte transendothelial migration: analysis of migrated cell
      phenotypes with regard to CD31 (PECAM-1), CD45RA and CD45RO.
AB  - CD31 is a 130,000 MW cell-surface glycoprotein expressed on endothelial cells,
      polymorphonuclear leucocytes, monocytes and about 50% of peripheral blood
      lymphocytes, and it has been proposed that it plays a role in transendothelial
      migration. If it is involved in endothelial transmigration of lymphocytes then
      the proportion of CD31+ cells should be increased in the lymphocyte population
      which has crossed an endothelial monolayer. This was tested using two endothelial
      types, namely human umbilical vein endothelial cells (HUVEC) and rat high
      endothelial venule (RHEV) cells. As a control, lymphocyte CD45RA and CD45RO
      expression was also determined since there is a correlation between lymphocytes
      bearing these isoforms and different migratory patterns. Double labelling
      techniques showed a close correlation between CD31 and CD45RA expression. With
      HUVEC monolayers, the transmigrated lymphocyte population was depleted of CD31+
      cells. This depletion was even more marked if the HUVEC monolayers had been
      stimulated with interleukin-1 beta (IL-1 beta). The migrated lymphocytes were
      enriched for CD31-CD45RO+ cells but depleted of CD31+CD45RA+ cells. In addition,
      lymphocyte populations depleted of CD31+ cells by immunopanning were also able to
      migrate across HUVEC monolayers. Taken together these data suggest that
      lymphocyte CD31 expression is not necessary for transmigration across HUVEC
      monolayers and, if anything, is negatively correlated with transmigration. With
      the second endothelial cell type, RHEV cells, there was no consistent change in
      the proportion of CD31+ lymphocyte in the transmigrated population, suggesting
      neither a positive nor a negative correlation between CD31+ expression and
      lymphocyte transmigration across RHEV cells. However, with both endothelial cell
      types, the migrated lymphocyte populations were enriched for the marker CD45RO.
      In conclusion, lymphocyte surface expression of CD31 is not necessary for
      transmigration across the endothelial cell types used in this study, but with
      both cell types an enrichment of CD45RO+ lymphocytes is seen in the migrated
      population.

PMID- 8307605
TI  - IgE antibody responses induced by transplantation of the nematode Nippostrongylus
      brasiliensis in rats: a possible role of nematode excretory-secretory product in
      IgE production.
AB  - In order to examine the effective site of sensitization for IgE responses, we
      transplanted 2000 adult-stage worms of the nematode Nippostrongylus brasiliensis
      into the duodenum or the peritoneal cavity of naive rats. Total serum IgE began
      to increase 1 week after the nematode inoculations and reached a peak at week 2.
      Living worms inoculated into the duodenum induced the highest serum IgE, this
      being 800 times the level in control animals. Intraperitoneal inoculations of
      living and dead worms resulted in increases of the serum IgE levels to 120 and 13
      times the control level, respectively. The intraduodenal inoculation of living
      adult worms also induced a significant increase in specific IgE against the
      excretory-secretory (ES) product of adult N. brasiliensis 1 week later than the
      rise in total IgE, whereas intraperitoneal inoculations did not induce such an
      increase. These results suggest that sensitization through the intestinal mucosa
      with adult N. brasiliensis might be important for the effective induction of both
      specific and non-specific IgE responses. Since these findings also indicated that
      factors secreted by living worms play an important role in the induction of total
      IgE response, the ES product was injected to naive rats for 6 consecutive days
      (total 2.7-4.4 mg). Intraperitoneal injection of the ES product alone induced a
      14.7-fold increase in total IgE without any specific IgE response. This indicates
      that some constituents of the ES product have the potential to trigger a non
      specific IgE response.

PMID- 8307607
TI  - Aberrant T-cell function in vitro and impaired T-cell dependent antibody response
      in vivo in vitamin A-deficient rats.
AB  - We have previously reported that vitamin A deficiency resulted in a reduced IgA
      antibody response to cholera toxin (CT) after per-oral immunization. In the
      present investigation we have studied the in vivo and in vitro immune response in
      vitamin A-deficient rats to two parenterally applied antigens, beta-lactoglobulin
      (beta-LG) and picrylsulphonic acid (TNP)-Ficoll. The serum IgG and IgM antibody
      responses to the T-cell dependent antigen beta-LG were significantly lower in the
      vitamin A-deficient rats than in the pair-fed control rats. No such differences
      were seen with the IgG and IgM responses to the T-cell independent antigen TNP
      Ficoll. However, the biliary IgA and the serum IgE antibodies against both
      antigens were decreased in the vitamin A-deficient rats. In vitro lymphocyte
      stimulation with concanavalin A (Con A) or beta-LG gave higher T-cell
      proliferation rates in the vitamin A-deficient than in the control rats.
      Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) levels in supernatants from
      Con A-stimulated mesenteric lymph node cells were also higher in the vitamin A
      deficient rats, while IL-6 levels were decreased, which is consistent with an up
      regulated Th1 activity. Proliferation studies on purified accessory cells and T
      cells from the deficient and the control rats, mixed in different combinations,
      showed that the T cells, but not the accessory cells, were disturbed in the
      vitamin A-deficient rats. Despite the increased T-cell activity in vitro the
      vitamin A-deficient rats had a lower delayed-type hypersensitivity (DTH) reaction
      than the pair-fed control rats. In conclusion, the increased IL-2 and IFN-gamma
      levels may reflect an up-regulation of Th1 cell function, while the decreased
      IgA, IgE and IL-6 levels indicate a suppression of Th2 cells. The disturbed T
      lymphocyte function is manifested in vivo as a decreased DTH reaction and
      suppressed antibody production, the latter possibly due to a lack of B-cell
      switching and proliferation factors in vitamin A-deficient rats.

PMID- 8307608
TI  - Chronic elevation of plasma corticosterone causes reductions in the number of
      cycling cells of the B lineage in murine bone marrow and induces apoptosis.
AB  - Steroid-containing implants were used to ascertain the effects of chronic
      elevation of physiological levels of plasma corticosterone (CS) (30-100
      micrograms/dl) on lymphopoietic processes in the bone marrow of the mouse.
      Phenotypic analysis of bone marrow B-lineage lymphocytes using flow cytometry
      (FACS) indicated a 50% decrease in bone marrow Ig+ cells, and a 70-80% decrease
      in B220+ cells had occurred 3 days after exposure to steroid. By day 5, the B220+
      Ig- precursor B cells in the marrow of mice exposed to CS were nearly depleted,
      with many of the remaining B cells being B220bright IgM+IgDbright. To determine
      if the depletion of B cells was due to disruption in cell cycling and/or
      induction of apoptosis, phenotype-gated FACS cell cycle analysis was utilized.
      The proportion of B220+ cells in the S phase of the cell cycle declined 75% after
      24 hr exposure to CS. A few hours after CS implantation, the appearance of a
      small but distinct population of B220+ and IgM+ cells in the 'hypodiploid' region
      of the cell cycle was also noted, which was previously termed the Ao region and
      corresponded to cells undergoing apoptosis. Thus, the chronic presence of
      modestly elevated levels of plasma CS analogous to that produced during
      malnutrition, stress and trauma caused rapid depletion of developing B-lineage
      cells in the marrow by reducing the number of cycling precursor B cells and
      inducing apoptosis.

PMID- 8307609
TI  - Antibodies to major histocompatibility complex class II inhibit proliferation,
      but increase production of soluble CD23 in lymphoblastoid B-cell lines.
AB  - Class II major histocompatibility complex (MHC) proteins bind and present peptide
      antigens to T cells. Moreover, their function as signal transduction molecules
      has recently been emphasized. Here we used Epstein-Barr virus (EBV)-transformed B
      cell lines (B-LCL) in experiments to investigate the changes induced by binding
      of specific antibodies to HLA-DR molecules. Binding of the antibodies induced, in
      an allele-specific manner, striking non-cytotoxic inhibition of B-LCL
      proliferation. This inhibition was associated with an increase in shedding of
      soluble CD23. These findings provide further evidence for the function of MHC
      class II proteins as signal transduction molecules which may be important in B
      cell activation.

PMID- 8307610
TI  - 'Subthreshold stimulation' of allospecific delayed hypersensitivity by corneal
      allografts.
AB  - Corneal allografts contain few or no Ia+ Langerhans' cells and consistently fail
      to elicit allospecific delayed-type hypersensitivity (DTH). The present study
      examined the hypothesis that the inability of corneal allografts to induce
      allospecific DTH was the result of active suppression. However, the results
      indicated that an initial exposure to corneal allografts provided a subthreshold
      stimulus for the induction of DTH because hosts that received a second pair of
      corneal grafts 7 days later developed DTH. By contrast, hosts that received all
      four corneal allografts simultaneously, failed to display DTH to donor
      alloantigens. Hosts that received a single set of corneal allografts did not
      display DTH to donor alloantigens, yet their spleen cells were capable of
      transferring DTH to hosts subsequently stimulated with a single set of corneal
      grafts. The capacity of Langerhans' cell-free corneal grafts to prime the host so
      that a second set of corneal grafts stimulated DTH to donor alloantigens was
      termed 'subthreshold stimulation of DTH'. The ability of sequential sets of
      corneal grafts to induce DTH was abolished by fixation with 0.2%
      paraformaldehyde. Surprisingly, the single cell-layered corneal endothelium was
      found to be the crucial corneal component necessary for the induction of
      allospecific DTH. This unique spectrum of corneal alloimmunogenicity may
      contribute to the immunological privilege and high success rate of corneal
      allografts.

PMID- 8307611
TI  - Cyclic AMP inhibits macrophage suppressor function and enhances lymphocyte
      proliferation.
AB  - The effects of increasing the level of cyclic AMP (cAMP) activity on lymphocyte
      proliferation in the rat mixed lymphocyte reaction (MLR) were investigated.
      Dibutyryl cAMP (dbcAMP) and prostaglandin E2 (PGE2) produced a dose-dependent
      reduction in proliferation in the lymph node (LN) MLR, but produced a substantial
      increase in proliferation in the spleen MLR at the lower concentrations used (10(
      5)-10(-4) M dbcAMP; 10(-7)-10(-6) M PGE2). Enhancement of proliferation was
      dependent on the presence of macrophages and was probably due to inhibition of
      macrophage activation. This was based on the following findings: (1) spleen MLR
      proliferation was lower than that in the LN MLR; (2) depletion of spleen
      macrophages increased proliferation in the spleen MLR and addition of these
      macrophages to the LN MLR reduced proliferation; (3) macrophage depletion from
      the spleen MLR abolished the proliferation-enhancing effect of dbcAMP. In
      conclusion, cAMP enhances lymphocyte proliferation in this system, apparently as
      a consequence of suppressing the inhibitory influence of macrophages.

PMID- 8307612
TI  - Regulation of murine macrophage function by IL-4: IL-4 and IFN-gamma
      differentially regulate macrophage tumoricidal activation.
AB  - To understand the differential role of interferon-gamma (IFN-gamma) and
      interleukin-4 (IL-4) in the process of macrophage tumoricidal activation, we
      investigated the production of tumor necrosis factor-alpha (TNF-alpha) and nitric
      oxide in activated murine macrophages and the effects of those lymphokines on
      prostaglandin E2 (PGE2)-mediated down-regulation. IFN-gamma and IL-4 increased
      lipopolysaccharide (LPS)-induced TNF-alpha production by different mechanisms
      because IL-4, unlike IFN-gamma, failed to overcome the LPS-hyporesponsiveness in
      C3H/HeJ mice. Moreover, only IFN-gamma synergized with LPS to induce nitric oxide
      production and blocked eicosanoid-mediated down-regulation. These differential
      effects of IFN-gamma and IL-4 on the select efferent cytolytic activities may be
      the result of an altered or different signal transduction pathway. Because
      potentiation of protein kinase C (PKC) activity by IFN-gamma has been previously
      documented, we next studied the role of IFN-gamma and IL-4 in alteration of
      enzymatic activity of PKC. Two lymphokines caused translocation of PKC from
      cytosol to membrane with different levels, providing a biochemical basis for
      explaining how two lymphokines lead to different phenotypic responses. Although
      treatment of macrophages with IFN-gamma and IL-4 gave rise to a similar enhancing
      effect on macrophage TNF-alpha production, these two lymphokines appeared to
      differentially regulate the overall functional state of macrophages for tumour
      cell killing capability. Additionally, this differential regulation seems to be
      accomplished in part by different biochemical events.

PMID- 8307613
TI  - Heterogeneity amongst natural killer cells revealed by limiting dilution culture;
      selectivity against virus-infected and tumour cell targets.
AB  - Previous studies have suggested that natural killer (NK) cells exhibit
      heterogeneous cytotoxicity towards different tumour cell targets. No studies have
      set out to determine whether different NK populations have relative selectivity
      for virus-infected cells. The aims of this study were to determine if this was
      the case for short-term clones, and whether there were differences in relative
      selectivity for particular target cells between clones with NK activity but with
      different surface phenotypes. Cells from different starting populations [whole
      peripheral blood lymphocytes (PBL), E-rosette positive or negative, CD16+ or CD3-
      cells] were grown in limiting dilution culture (LDC) with interleukin-2 (IL-2).
      The precursor frequency (NK-p) of cells proliferating and exhibiting NK activity
      towards various virus-infected or uninfected fibroblasts or tumour cell targets
      was determined by split-well analysis of the LDC. The relative NK-p were similar
      for different individuals, but were much lower for virus-infected fibroblasts
      than a tumour cell target. The pattern of cytotoxicity of 757 short-term clones,
      identified from the LDC, against four to five tumour and virus-infected target
      cells were analysed. We conclude that there was selective lysis of virus-infected
      cells by a proportion of NK clones which were predominantly PBL-derived (mainly
      CD3+). Twenty-six per cent of E(+)-derived clones lysed Molt4 cells only in the
      absence of phytohaemagglutinin (PHA), and a proportion of PBL- or E(+)-derived
      clones (up to 44%) lysed uninfected or virus-infected fibroblasts but not
      Molt4+PHA. Thus, under hese conditions lectin-induced cytotoxicity does not
      detect total potential cytotoxicity.

PMID- 8307614
TI  - The role of the phosphatidylinositol turnover in 12-hydroxyeicosatetraenoic acid
      generation from human platelets by Escherichia coli alpha-haemolysin, thrombin
      and fluoride.
AB  - Activation of human platelets with either the Escherichia coli alpha-haemolysin
      or thrombin, or with pharmacological agonists such as sodium fluoride (NaF), Ca
      ionophore A23187 or phorbol myristate acetate (PMA), induced a similar pattern of
      serotonin release, unlike 12-hydroxyeicosatetraenoic acid (12-HETE) generation.
      In the presence of neomycin (0.1, 1, 10 mM), an inhibitor of the
      phosphatidylinositol-specific phospholipase C (PIP2-PLC), the E. coli alpha
      haemolysin-induced 12-HETE generation was enhanced up to threefold in a dose
      dependent manner. 12-HETE generation by NaF and thrombin was slightly inhibited
      at high neomycin concentrations (10 mM). Treatment of human platelets with E.
      coli alpha-haemolysin induced a different activation pattern of PIP2-PLC and
      phosphatidylinositol4-kinase (PI4-kinase), compared to NaF and thrombin.
      Haemolysin treatment resulted in a down-regulation of PIP2-PLC and PI4-kinase
      enzymatic activities by 20 +/- 9/40 +/- 8% compared to unstimulated cells; the
      decrease in enzymatic activities was observed within 2 min of stimulation and was
      still apparent after 60 min of stimulation. In NaF- and thrombin-stimulated
      platelets, dose- and time-dependent increases in PIP2-PLC (by up to 21 +/- 10%,
      34 +/- 11%, respectively) and PI4-kinase (by up to 71 +/- 18, 54 +/- 14)
      activities were measured. Maximal enzymatic activities were reached after 5-20
      min of stimulation (NaF, thrombin) followed by a decline to baseline levels
      (thrombin) or below baseline levels (NaF). Our results indicate that the
      phosphatidylinositolphosphate metabolism plays an important role in the
      regulation of 12-HETE release from human platelets by E. coli alpha-haemolysin.

PMID- 8307615
TI  - Binding ability of complement receptor CR1 to C3 bound on the surface of M+ group
      A streptococci.
AB  - A previous study demonstrated that although M+ bacteria bound C3, mainly C3b and
      iC3b, via the classical pathway of complement activation, they were not
      phagocytosed by polymorphonuclear leucocytes (PMN). To elucidate this mechanism,
      we attempted to distinguish between the possibilities that M+ bacteria are
      effectively adhering to PMN but are not being endocytosed, or that the C3
      deposited on M+ bacteria is not able to interact with the complement receptors on
      PMN. In the present study, we studied the interaction of C3-coated M+ bacteria
      with complement receptor CR1, which was isolated from the stroma of human
      erythrocytes. We show that the isolated complement receptor CR1 can associate
      with C3-coated M+ bacteria as well as with C3-coated M- bacteria, and the C3
      deposited on M+ bacteria is cleaved and releases a C3 fragment in the presence of
      factor I and liquid-phase CR1. These results suggest that the C3 bound on the
      surface of M+ bacteria is able to promote adherence to the complement receptor
      CR1 on PMN. We also studied the distribution of C3 deposited on M+ bacteria in
      normal human serum (NHS) or normal human plasma (NHP). By immunofluorescence, we
      show that the C3 bound to M+ bacteria in NHS was deposited uniformly over the
      surface of the bacteria. On the other hand, the C3 bound to M+ bacteria in NHP
      was deposited at both ends between adjacent daughter cocci. The results suggest
      that an additional factor contained in NHP is related to the enhancement of anti
      phagocytic activity of M+ bacteria.

PMID- 8307616
TI  - Regulation of CD3 expression in a protein kinase C isozyme-deficient T-cell line.
AB  - Using the T-cell lymphoma line HuT 78, and a clone derived from HuT 78,
      designated K-4, the role of protein kinase C (PKC) isozymes in the expression of
      a variety of T-cell surface antigens was investigated. HuT 78 expresses PKC
      isozymes alpha and beta while K-4 expresses only PKC alpha. Flow cytometric
      analysis revealed that incubation of HuT 78 cells with phorbol 12-myristate 13
      acetate (PMA) results in significant down-regulation of surface expression of
      CD3. While K-4 cells expressed reduced amounts of CD3, a similar reduction in CD3
      expression was not observed when these cells were stimulated with PMA. The
      regulation of expression of CD11a (LFA-1), CD44, CD45RA and CD45RO and of the
      class II molecules DR and DP in response to PMA, was similar in both cell lines.

PMID- 8307617
TI  - Requirement for tyrosine phosphorylation in lipopolysaccharide-induced murine B
      cell proliferation.
AB  - Bacterial lipopolysaccharide (LPS) induces a strong B-cell proliferative response
      with subsequent differentiation, through a complex signal transduction pathway.
      This process is known to be mediated through protein kinase C (PKC) translocation
      without Ca2+ mobilization. Here, we show that B-cell proliferative responses
      induced by five different LPS preparations, as well as by F(ab')2 anti-IgM
      antibodies, are inhibited by the tyrosine kinase inhibitors, genistein and
      herbimycin A. In contrast, B-cell proliferation induced by the combination of
      phorbol 12-myristate 13-acetate (PMA) plus ionomycin was not influenced by
      treatment with either herbimycin A or genistein. These data indicate that
      tyrosine phosphorylation is required to initiate B-cell proliferation by LPS.

PMID- 8307618
TI  - Mls-1 and Mls-2 superantigens do not control susceptibility to collagen-induced
      arthritis in HI and HII mice.
AB  - The HI mouse line is sensitive to collagen-induced arthritis (CIA), whereas HII
      is refractory, although both express the H-2q permissive haplotype. The two lines
      also share the same T-cell receptor (TcR) gene haplotypes for alpha and beta
      chains. The distribution of mouse mammary tumour viruses (MMTV), which encode
      endogenous superantigens (SAg) such as minor leucocyte-stimulating antigens (Mls)
      known to modulate the available TcR-V beta repertoire, was investigated in the
      two lines. Mls-1 is present in HI-susceptible mice, while Mls-2 and Mls-2-like
      SAg are absent in both lines. This suggests that Mls antigens play no significant
      role in the resistance to CIA. Moreover, HI and HII exhibit close V beta gene
      usage as assessed by fluorescence staining with 11 V beta-specific monoclonal
      antibodies (mAb). These results indicate that mechanisms other than clonal
      deletion based on V beta expression and induced by SAg are involved in the
      resistance of H-2q-positive mice to experimental arthritis. Yet, a slightly
      reduced level of V beta 5+ T cells is observed in HII animals which might
      correlate with the presence of Mtv-6 and Mtv-9 proviruses.

PMID- 8307619
TI  - Xenogenic transfer of human lymphocytes in tolerized mice.
AB  - Female nu/+ or BALB/c mice were immunized with human peripheral blood lymphocytes
      (PBL) before and during pregnancy. Pups born to these mothers were inoculated
      with human PBL or human fetal bone marrow and thymus cells. Tolerization of the
      pups to human PBL was observed without graft-versus-host reaction. Presence of
      human immunoglobulins was observed in the pups for 3-4 weeks. Human T cells also
      could be detected for a period of 3-4 months in these mice.

PMID- 8307621
TI  - Toward a more effective and efficient communication process.

PMID- 8307620
TI  - Localization of IFN-gamma and IL-6 mRNA in murine intestine by in situ
      hybridization.
AB  - Previous studies have highlighted the importance of CD4+ T cells in regulation of
      IgA responses and have indicated a functional heterogeneity among these cells
      between inductive (Peyer's patch) and effector (lamina propria) sites in the
      intestine. To determine whether these functional differences could be accounted
      for by differences in cytokine profile of cells in each of these sites, the
      distribution of mRNA for interferon-gamma (IFN-gamma) and interleukin-6 (IL-6)
      was investigated by in situ hybridization techniques using 35S-labelled
      riboprobes. Whereas message for IL-6 is abundant in all regions of the lamina
      propria from the base of the mucosa to the tips of the villi, very little is
      expressed in Peyer's patches or in the epithelium. In contrast, message for IFN
      gamma is expressed predominantly by cells localized only in the base of the
      lamina propria and, as with IL-6, very little message was detected in Peyer's
      patches although occasional strongly positive IFN-gamma cells were observed in
      the epithelium. These results indicate that, at least in the absence of
      deliberate intestinal stimulation, functional expression of these cytokines is
      restricted to effector rather than induction sites in the intestine. This is
      consistent with our previous observations demonstrating a requirement for T-cell
      signals in promoting post-extravasation differentiation and proliferation of IgA
      committed B cells in vivo and the implications of these findings to the role of
      the Th1 and Th2 subsets of CD4+ cells in mucosal immune responses is discussed.

PMID- 8307622
TI  - National High Blood Pressure Education Program Working Group report on
      hypertension in diabetes.
AB  - Hypertension and diabetes mellitus are interrelated diseases that, if untreated,
      strongly predispose to atherosclerotic cardiovascular disease and renal disease.
      More than 3 million Americans have both hypertension and diabetes, which are
      particularly prevalent in the socioeconomically disadvantaged. Hypertension
      contributes substantially to morbidity and mortality in people with diabetes.
      This report is an update of the 1987 working group report on hypertension and
      diabetes and includes important new information on the management of hypertension
      in people with diabetes. Although treatment of hypertension in most people with
      diabetes does not differ from that in people who do not have diabetes, this
      report outlines some special considerations relevant to the presence of both
      diseases. Lifestyle modification is considered as an initial treatment modality
      or as an adjunct to pharmacologic measures. This report also includes a
      discussion of the treatment of hypertension and diabetes in children, an expanded
      review of sexual dysfunction, and an increased emphasis on the effect of
      hypertension and diabetes on target organs. A treatment algorithm represents a
      practical guideline for the physician. Since the previous report, there has been
      an increased awareness, through clinical trials and pharmacologic research, of
      the importance of flexibility in the use of antihypertensive drugs as well as a
      refinement of nonpharmacologic approaches in treating people with both
      hypertension and diabetes.

PMID- 8307623
TI  - Hypertension in the spontaneously hypertensive rat and the sex chromosomes.
AB  - We investigated the involvement of loci on the sex chromosomes in the
      hypertension of the spontaneously hypertensive rat (SHR) by studying male F1 and
      F2 generation rats derived from reciprocal crosses of SHR with Wistar-Kyoto (WKY)
      rats (cross 1: WKY female x SHR male; cross 2: SHR female x WKY male). At 16
      weeks of age there was no significant difference in the blood pressures of F1
      animals derived from the two crosses. Similarly, in the F2 generation there was
      no significant difference in either indirect blood pressures measured at 12, 16,
      or 20 weeks of age or in direct systolic and diastolic blood pressures measured
      at 25 weeks of age between animals derived from the two crosses maintained on a
      normal salt diet. In a second study, cohorts of F2 rats from the two crosses were
      given 1% salt in their drinking water for 10 weeks from 16 weeks of age with
      indirect blood pressure measurements at 16 (presalt), 18, and 20 weeks and direct
      blood pressure measurements at 26 weeks. Although overall these animals had
      significantly higher blood pressures at both 20 and 26 weeks than animals of the
      first study, again there was no difference in blood pressures of animals derived
      from the two crosses, apart from a marginally significantly higher blood pressure
      at 18 weeks in animals from cross 1 (with SHR grandfather). The findings indicate
      that the sex chromosomes of the SHR and WKY rat used in these crosses do not
      contain loci where alleles differentially influence blood pressure under the
      genetic milieu provided by the cross.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307624
TI  - Systemic hemodynamics during sleep in young or middle-aged and elderly patients
      with essential hypertension.
AB  - Age-related changes in cardiovascular regulatory mechanisms may affect blood
      pressure homeostasis during sleep and in the daytime. This study compared
      systemic hemodynamics during the daytime and sleep between 12 young or middle
      aged patients (young, 42.1 +/- 13.9 years old, mean +/- SD, less than 56 years
      old) and 12 elderly patients with essential hypertension (old, 65.3 +/- 2.8, 60
      to 70 years old). They were all hospitalized and placed on a diet containing
      approximately 7 g sodium chloride per day. Intra-arterial blood pressure and
      electrocardiogram were recorded for 24 hours, and electroencephalogram and
      electroophthalmogram were recorded during the night with a telemetric method.
      Cardiac output was measured with patients in the supine position by the cuvette
      method during the daytime and stage 3 or 4 sleep at night. The averaged 24-hour
      blood pressure was similar in the two groups (140 +/- 2 [SEM]/85 +/- 3 mm Hg in
      the young group and 144 +/- 4/81 +/- 2 mm Hg in the old group). The reduction in
      mean blood pressure during sleep was also comparable in both groups (-18 +/- 2 in
      the young group and -20 +/- 2 mm Hg in the old group). Cardiac index was smaller
      in the old group than the young group during both the daytime and sleep (daytime,
      2.3 +/- 0.1 versus 3.2 +/- 0.2 [L/min]/m2, P < .01; sleep, 2.1 +/- 0.1 versus 2.6
      +/- 0.2 [L/min]/m2, P < .01). The reduction in cardiac index during sleep was
      greater in the young than the old group (P < .05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8307625
TI  - Dose-related effects of magnesium on myocardial function in the neonate.
AB  - The antagonistic effects of magnesium ion as a calcium ion blocker may decrease
      calcium influx associated with ischemia. However, the effect of magnesium on the
      preischemic neonatal myocardium has not been investigated previously. The purpose
      of this study was to investigate the effects of the administration of increasing
      doses of magnesium on left ventricular performance in the neonate. We assessed
      left ventricular function (pressure-volume data obtained by the conductance
      catheter/micromanometer technique) in three groups (n = 6 in each) of newborn
      pigs (3 to 5 days old) differing with respect to magnesium concentrations. End
      systolic elastance did not change during infusion in group A (magnesium = 1.2
      mmol/L), whereas in groups B (magnesium = 8 mmol/L) and C (magnesium = 16 mmol/L)
      it decreased significantly (P < .05) to 67 +/- 6% and 44 +/- 8% of baseline,
      respectively. The decrease in end-systolic elastance was associated with a
      significant reduction in cardiac output (P < .05) and stroke work (P < .05) in
      group C. After administration of magnesium, end-systolic elastance returned to
      baseline in group B in contrast to group C (78 +/- 3% of baseline value, P <
      .05). The slope constant of the end-diastolic pressure-volume relation decreased
      significantly (P < .05) from the preinfusion baseline values of 0.42 +/- 0.08 mL
      1 in group B and 0.46 +/- 0.05 mL-1 in group C to 0.3 +/- 0.04 and 0.26 +/- 0.03
      mL-1, respectively, versus no change in group A.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307626
TI  - Regulation of aldosterone secretion in hypertensive blacks.
AB  - Hypertension in blacks is common, often severe, and largely unexplained. Recent
      studies have suggested that aldosterone secretion in blacks may be reduced,
      whereas older data demonstrate no racial differences in aldosterone excretion. We
      performed this study to examine adrenal responsiveness in black hypertensive
      patients under controlled metabolic conditions. Thirty-one black hypertensive
      patients and 7 black normotensive subjects were studied on intakes of 10 mmol/d
      sodium and 100 mmol/d potassium, with the renin-angiotensin-aldosterone system
      further stimulated by upright posture or infusion of angiotensin II (Ang II).
      Forty-six hypertensive and 14 normotensive whites underwent the same protocol as
      a comparison group. Hypertensive blacks and whites had similar mean basal plasma
      aldosterone levels on a low salt diet, lower in both groups than in normotensive
      subjects. In the black patients, however, plasma aldosterone responses were
      significantly lower than responses in white hypertensive patients when further
      stimulated by either posture (1451 +/- 216 versus 2571 +/- 225 pmol/L [52.3 +/-
      7.8 versus 92.7 +/- 8.1 ng/dL], P < .002) or Ang II infusion (843 +/- 122 versus
      1617 +/- 189 pmol/L [30.4 +/- 4.4 versus 58.3 +/- 6.8 ng/dL], P < .001). Renin
      status did not account for the difference. Basal and stimulated plasma
      aldosterone concentrations, on the other hand, were similar in normotensive white
      and black subjects. Blunted adrenal responses to upright posture and Ang II
      infusion are common among black hypertensive patients. These abnormalities may be
      part of a larger constellation of abnormalities in blacks, reflecting perhaps a
      greater, more frequent underlying disturbance in salt handling than in whites.

PMID- 8307627
TI  - Long-term cardiovascular role of nitric oxide in conscious rats.
AB  - The goal of this study was to determine the arterial pressure and renal excretory
      responses to a continuous intravenous infusion of 7.4 nmol/kg per minute of the
      nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in
      conscious rats. Studies were conducted in six groups of Sprague-Dawley rats with
      indwelling arterial and venous catheters over periods lasting 12 to 26 days. In
      the first group of rats, L-NAME infusion for 9 days caused a sustained increase
      in arterial pressure, and on the ninth day arterial pressure was increased 29 mm
      Hg. Infusion of L-NAME at the higher dose of 37 nmol/kg per minute for 9 days
      caused no greater increase in arterial pressure than the lower dose. Sodium and
      volume balances and phenylephrine pressor sensitivity were unchanged during L
      NAME administration at 7.4 nmol/kg per minute; plasma renin activity increased
      2.5-fold, but the vasodepressor and vasodilator responses to acetylcholine and
      bradykinin were unchanged. Arterial pressure remained significantly increased 7
      days after L-NAME was stopped, but in another group of rats, intravenous L
      arginine infusion caused arterial pressure to return to control within 1 day.
      This same dose of L-arginine was administered for 7 days intravenously, and
      neither arterial pressure nor sodium balance changed. In other groups of rats, L
      arginine was administered in conjunction with L-NAME; this prevented any change
      in arterial pressure, whereas D-arginine did not. In conclusion, the data suggest
      that continuous intravenous infusion of L-NAME causes sustained increases in
      arterial pressure in conscious rats without any sodium or water retention. The
      hypertension is accompanied by increases in plasma renin activity and can be
      prevented with intravenous L-arginine administration.

PMID- 8307628
TI  - Microalbuminuria in salt-sensitive patients. A marker for renal and
      cardiovascular risk factors.
AB  - We previously showed that a high salt diet increases glomerular capillary
      pressure in salt-sensitive hypertensive patients and suggested that this may
      underlie the greater propensity of these patients to develop renal failure.
      Because microalbuminuria is considered an initial sign of renal damage, we have
      tested whether salt-sensitive patients display greater urinary albumin excretion
      than salt-resistant hypertensive patients. Twenty-two patients were placed on a
      low sodium intake (20 mEq/d) for 7 days followed by a high sodium diet (250
      mEq/d) for 7 more days. Twelve patients were classified as salt sensitive and 10
      as salt resistant. Urinary albumin excretion was greater in salt-sensitive than
      salt-resistant patients (54 +/- 11 versus 22 +/- 5 mg/24 h, P < .01). During the
      low sodium diet, glomerular filtration rate, renal plasma flow, and filtration
      fraction were similar between the two groups. During the high sodium intake,
      glomerular filtration, renal plasma flow, filtration fraction, and calculated
      intraglomerular pressure did not change in salt-resistant patients; in salt
      sensitive patients, however, renal plasma flow decreased, and filtration fraction
      and intraglomerular pressure increased, whereas glomerular filtration rate did
      not change. Urinary albumin excretion was significantly correlated with
      glomerular capillary pressure. Salt-sensitive patients displayed higher serum
      levels of low-density lipoprotein cholesterol and lipoprotein(a) and lower levels
      of high-density lipoprotein cholesterol than salt-resistant patients. These
      studies have shown greater urinary albumin excretion and serum concentrations of
      atherogenic lipoproteins in salt-sensitive than in salt-resistant hypertensive
      patients, suggesting that salt sensitivity may be a marker for greater risk of
      renal and cardiovascular complications.

PMID- 8307629
TI  - OPC-21268, a vasopressin V1 antagonist, produces hypotension in spontaneously
      hypertensive rats.
AB  - We studied the hypotensive effects of OPC-21268, an orally effective nonpeptide
      vasopressin V1 receptor antagonist, in spontaneously hypertensive rats (SHR) and
      stroke-prone SHR (SHRSP). OPC-21268 was given intravenously to conscious, freely
      moving SHR and SHRSP. We used young and aged animals to examine the contribution
      of vasopressin to the development and maintenance of hypertension in both types
      of rats. In SHR, hypertension was fully established at 38 weeks of age, and
      intravenous injection of OPC-21268 produced slight hypotensive effects at either
      38 or 70 weeks of age. In SHRSP, hypertension developed at 25 weeks of age, and
      blood pressure was sustained at a high level (approximately 250 mm Hg systolic
      blood pressure) thereafter. Intravenous administration of OPC-21268 did not cause
      hypotensive effects in young rats at 15 weeks, but at 25 weeks a significant
      decrease in blood pressure was observed. Furthermore, in the malignant state of
      SHRSP (35 to 41 weeks), OPC-21268 significantly decreased mean blood pressure by
      32.4 +/- 7.9 mm Hg (mean +/- SEM) at 3 mg/kg IV, and the decrease was dose
      dependent (0.3 to 3.0 mg/kg). Plasma vasopressin concentrations were increased in
      a more malignant phase of SHRSP at 45 weeks of age, whereas at other ages of
      SHRSP or in SHR, plasma vasopressin levels were not increased. These results
      suggest that vasopressin plays an important role through V1 receptors in the
      maintenance of hypertension, at least in the malignant phase of SHRSP, and OPC
      21268 may be therapeutically useful in the treatment of some types of
      hypertension.

PMID- 8307630
TI  - Endothelin blockade lowers total peripheral resistance in hemorrhagic shock
      recovery.
AB  - To determine whether endothelin (ET) has a role in maintaining circulatory
      support during hypotensive hemorrhage, we (1) examined cardiac and systemic
      hemodynamics after a 6-mL hemorrhage in the presence and absence of the ETA
      receptor blocker BQ-123, (2) examined cardiac and systemic hemodynamics during BQ
      123 infusion in nonhemorrhaged rats, (3) measured changes in circulating
      immunoreactive endothelin (IR-ET) after a 6-mL hemorrhage, and (4) infused
      pathophysiological doses of ET-1 into rats anesthetized with thiobutabarbital.
      Twenty minutes after hemorrhage, cardiac output and mean arterial pressure had
      stabilized in part because of an increase in systemic vascular resistance from
      0.86 +/- 0.04 (baseline) to 1.04 +/- 0.05 (20 minutes) mm Hg/mL per minute. The
      rise in systemic vascular resistance was temporally associated with a significant
      (24%) increase in circulating IR-ET from 29 +/- 2 to 36 +/- 3 pg/mL 20 minutes
      after hemorrhage. During BQ-123 infusion mean arterial pressure at 5, 10, and 20
      minutes after hemorrhage was 9 +/- 2, 23 +/- 4, and 23 +/- 3 mm Hg lower than
      values obtained after hemorrhage alone (P < .05). Mean arterial pressure was
      unaffected by BQ-123 infusion at baseline and 30 minutes after hemorrhage.
      Systemic vascular resistance was not affected at baseline by BQ-123 infusion.
      However, systemic vascular resistance was significantly lower 5, 10, 20, and 30
      minutes after hemorrhage during BQ-123 infusion compared with hemorrhage alone at
      each time point. Infusion of BQ-123 into nonhemorrhaged rats had no effect on
      mean arterial pressure, systemic vascular resistance, or cardiac output.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8307631
TI  - Factors affecting ambulatory blood pressure reproducibility. Results of the
      HARVEST Trial. Hypertension and Ambulatory Recording Venetia Study.
AB  - To assess the reproducibility of ambulatory blood pressure, we recorded 24-hour
      blood pressure twice 3 months apart in 508 hypertensive subjects participating in
      the HARVEST trial using a noninvasive technique. Blood pressure was measured
      every 10 minutes during the daytime and 30 minutes during the nighttime.
      Reproducibility was better for ambulatory than for office blood pressure. It was
      greater for 24-hour than for daytime blood pressure and lowest for nighttime
      blood pressure. The reproducibility of blood pressure variability (standard
      deviation) was poorer than that of the average values. A small but significant
      decrease in average daytime blood pressure (-0.8/-1.0 mm Hg) and virtually no
      change in nighttime blood pressure (+0.5/+0.1 mm Hg) were observed at repeat
      recording. Reducing the sampling rate by 50% caused only a small impairment of
      the reproducibility indexes of both the average values and variability. Blood
      pressure reduction was greater during the first and last hours of the recordings,
      indicating an effect of the hospital environment on the between-monitoring
      difference. Changes in body weight (-0.7 kg, P = .006, at repeat recording) were
      related to those of 24-hour diastolic blood pressure (P < .05). In conclusion,
      patient reaction to medical environment and changes of body weight seem to
      account for most of the change in 24-hour blood pressure that occurs over a 3
      month period.

PMID- 8307632
TI  - Inhibition of vasopressin action in vascular smooth muscle by the V1 antagonist
      OPC-21268.
AB  - In vascular smooth muscle cells arginine vasopressin acting through the V1
      receptor increases intracellular Ca2+, leading to vasoconstriction. Recent
      studies have also shown that vasopressin activates mitogen-activated protein
      kinase (MAP kinase), which may contribute to vasopressin-induced hypertrophy of
      vascular smooth muscle cells. We examined the ability of an orally active,
      nonpeptide selective V1 antagonist (OPC-21268) to block vasopressin binding and
      postreceptor signaling in these cells. [3H]Vasopressin binding at 2 x 10(-9)
      mol/L was half-maximally blocked at 10(-9) mol/L OPC-21268. To compare effects of
      OPC-21268 on binding and postreceptor signaling, we stimulated cells with 10(-8)
      mol/L vasopressin. At this vasopressin concentration, half-maximal inhibition of
      binding occurred at 5 x 10(-9) mol/L OPC-21268. Half-maximal inhibition of Ca2+
      efflux or increases in intracellular free Ca2+ required higher concentrations of
      antagonist (10(-7) mol/L), and half-maximal inhibition of vasopressin-stimulated
      MAP kinase was observed only at 10(-6) mol/L OPC-21268. These results indicate
      that this agent selectively blocks both vasopressin binding and postreceptor
      signaling in vascular smooth muscle cells. The requirement of higher
      concentrations of OPC-21268 for blocking increases in intracellular Ca2+ and
      activation of MAP kinase suggests that binding to a fraction of V1 receptors
      generates maximal levels of second messengers or the existence of subtypes of the
      V1 receptor with differential affinity for this antagonist. These data have
      implications for the clinical use of this compound.

PMID- 8307633
TI  - Pressure-flow curves reflect arteriolar responses in perfused rat hindquarters.
AB  - Results from studies using pump-perfused rat hindquarters are consistent with
      increased wall-to-lumen ratios in resistance vessels of spontaneously
      hypertensive rats (SHR). However, in vivo measurements of cremaster arterioles
      have not shown increased wall-to-lumen ratios in SHR. To investigate this
      discrepancy, we studied three groups of male SHR and Wistar-Kyoto rats at 12
      weeks of age. In the first two groups, the cremaster muscle was prepared to allow
      microscopic observation while the hindquarters were pump-perfused with increasing
      concentrations of norepinephrine in oxygenated Tyrode's solution. Both groups of
      SHR showed an increase in vasodilated resistance and elevated maximal
      vasoconstrictor response. In the first group, arterioles showed dose-dependent
      constriction that was greater in smaller arterioles but did not differ between
      hypertensive and normotensive rats. Vasodilated diameters of second-order
      arterioles were significantly smaller in the hypertensive rats. In the second
      group, servo-null pressures in the first-order arteriole showed that the
      microvessels contributed proportionally to the elevation in resistance in both
      SHR and normotensive rats. In the third group, first- and second-order arterioles
      were measured in vivo and histologically. Arteriolar diameters did not differ
      between SHR and normotensive rats with either method. In fixed sections the cross
      sectional area of the media-intima was greater in the SHR. Therefore, data from
      the pump-perfused rat hindquarters accurately reflect vasoconstrictor responses
      of the arterioles, and in deference to in vivo measurements on arteriolar walls
      that include the adventitia, the increased response in the SHR can be explained
      by hypertrophy of the arteriolar medial-intimal area.

PMID- 8307634
TI  - Role of superoxide anions in the mediation of endothelium-dependent contractions.
AB  - We designed experiments to characterize the role of superoxide anions in the
      mediation of endothelium-dependent contractions in isolated canine basilar
      arteries. Rings with and without endothelium were suspended for isometric tension
      recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (37
      degrees C, pH 7.4). Radioimmunoassay was used to determine the levels of cyclic
      GMP and cyclic AMP. Calcium ionophore A23187 (10(-9) to 10(-6) mol/L) caused
      concentration-dependent contractions. The removal of endothelium abolished the
      effect of A23187. Contractions to A23187 were reversed into relaxations in the
      presence of superoxide dismutase (150 U/mL) or the prostaglandin H2/thromboxane
      A2 receptor antagonist SQ29548 (10(-6) mol/L). NG-nitro-L-arginine methyl ester
      (3 x 10(-4) mol/L) augmented contractions to A23187. In rings with endothelium,
      A23187 (3 x 10(-7) mol/L) significantly increased levels of both cyclic AMP and
      cyclic GMP. Indomethacin (10(-5) mol/L) inhibited stimulatory effects of A23187
      on cyclic AMP production. In contrast, indomethacin augmented A23187-induced
      production of cyclic GMP. Selective augmentation of cyclic GMP production by
      indomethacin appears to be due to protection of nitric oxide or a closely related
      molecule released following translocation of calcium into endothelial cells. Our
      findings suggest that (1) an increased concentration of calcium in endothelial
      cells may activate both cyclooxygenase and the L-arginine/nitric oxide pathway,
      (2) arachidonic acid metabolism via cyclooxygenase is a source of superoxide
      anions, and (3) superoxide anions may be responsible for impairment of balance
      between relaxing and contracting factors leading to contraction of underlying
      smooth muscle cells.

PMID- 8307635
TI  - Twenty-four-hour blood pressure and heart rate profiles in humans. A twin study.
AB  - To delineate the relative roles of genetic and environmental factors on
      physiological variations of blood pressure and heart rate, we performed 24-hour
      ambulatory blood pressure monitorings with simultaneous polygraphic sleep
      recordings in 28 monozygotic and 16 dizygotic healthy young male twin pairs
      investigated in a standardized physical and social environment. Blood pressure
      and heart rate were measured every 10 minutes for 24 hours. A best-fit curve
      based on the periodogram method was used to quantify changes in blood pressure
      and heart rate over the 24-hour span. Surprisingly, monozygotic twins as a group
      tended to have higher blood pressure values than dizygotic twins, and this
      difference reached the level of significance for daytime systolic blood pressure
      (P < .005). Although environmental influences largely controlled the mean levels
      and characteristics of the 24-hour systolic blood pressure variations,
      significant genetic effects were demonstrated for the mean levels and 24-hour
      patterns of diastolic blood pressure and heart rate. For both diastolic blood
      pressure and heart rate, the genetic effects concerned largely the same
      characteristics of the 24-hour profiles: the 24-hour mean, the daytime mean, the
      value of the evening acrophase, and the value of the major acrophase. Moreover,
      there was a strong genetic influence for the amplitude of the 24-hour rhythm of
      heart rate.

PMID- 8307636
TI  - Potential problems with the random-zero sphygmomanometer.
AB  - The random-zero sphygmomanometer is frequently used in epidemiologic and clinical
      research to increase the reliability and validity of blood pressure readings.
      However, recent reports have suggested that there is a correlation between the
      zero values of a random-zero sphygmomanometer and the zero-corrected blood
      pressure readings obtained. The design of the random-zero sphygmomanometer would
      suggest that the zero values and zero-corrected blood pressures should be
      uncorrelated. Hence, residual correlation might be of importance in determining
      the utility of this device. We have explored this relation in the Middlesex
      County Blood Pressure Survey, which collected data on 2725 randomly selected
      adults. Each person had three blood pressure readings taken with a random-zero
      sphygmomanometer operated by trained interviewers. There was a very weak but
      statistically significant correlation between the zero values and zero-corrected
      systolic blood pressure (r = .034, regression slope = -.10), but there was no
      statistically significant relation with zero-corrected diastolic blood pressure
      (r = .0003, slope = .0006). Both the correlations and regression slopes were
      higher for subjects over age 65 years. These data fail to confirm the observed
      correlations found by Kronmal et al. This discrepancy might be explained by
      differences in measurement technique, which could introduce a blood pressure
      dependent skewing of the range of zero values. If confirmed, this effect would
      have no effect on the validity of the final blood pressure readings and hence
      would not need to be considered in decisions about the use of the random-zero
      sphygmomanometer.

PMID- 8307637
TI  - Tissue angiotensin converting enzyme in cardiac and vascular hypertrophy, repair,
      and remodeling.

PMID- 8307638
TI  - Inverse association between baseline pressure and benefit from treatment in
      isolated systolic hypertension.

PMID- 8307639
TI  - The problem of gastrointestinal bleeding.
AB  - Gastrointestinal bleeding accounts for more than 300,000 hospital admissions per
      year in the United States. Despite the introduction of an array of novel
      diagnostic and therapeutic approaches, the mortality rate associated with
      gastrointestinal bleeding has remained stable at 5% to 12%, primarily because of
      the rising percentage of elderly patients with gastrointestinal bleeding and the
      high mortality of bleeding that occurs during the course of a hospitalization for
      an unrelated medical problem. With defined high-risk subgroups of patients and
      competing diagnostic and therapeutic techniques, the study of gastrointestinal
      bleeding lends itself almost ideally to the application of outcomes and
      effectiveness research.

PMID- 8307640
TI  - Bleeding peptic ulcer: pathogenesis and endoscopic therapy.
AB  - The presence of stigmata of hemorrhage in a peptic ulcer indicate an increased
      risk of rebleeding and the need for endoscopic intervention. Clinical trials
      indicate that laser photocoagulation, multipolar and heater probe coagulation,
      and injection therapy are all effective in decreasing bleeding from peptic ulcer
      disease. The modality used for the individual patient depends on available
      resources and the experience of the endoscopist. Laser photocoagulation is used
      infrequently, not because of a lack of efficacy but because of its increased cost
      and impracticality, including its lack of portability. Multipolar coagulation and
      heater probe coagulation are commonly employed but may give way to injection
      therapy as first-line therapy, because it is equally effective, cost less, and is
      easy to implement in a variety of clinical settings.

PMID- 8307641
TI  - Bleeding peptic ulcer: surgical therapy.
AB  - The management of bleeding peptic ulcer disease varies with multiple clinical and
      endoscopic variables. For the patient with rapid hemorrhage and hemodynamic
      instability refractory to endoscopic control, operation clearly is indicated. For
      patients with a low probability of recurrent ulcer hemorrhage because of the
      absence of endoscopic stigmata or clinical predictors of further ulcer bleeding,
      nonoperative management with selective use of endoscopic hemostasis is
      appropriate. For the remaining patients with a moderate risk of recurrent ulcer
      hemorrhage, the clinician must use what is known of the clinical and endoscopic
      predictors of recurrent hemorrhage and arrive at a judgment regarding the
      selective use of endoscopic hemostasis and subsequent early operation. For
      elderly patients with a large duodenal or gastric ulcer who have experienced
      significant blood loss precipitating an episode of hypovolemic shock and who have
      endoscopic stigmata of ulcer hemorrhage, early elective operation after
      endoscopic hemostasis is the most judicious course. Surgery also is the wise
      choice for those patients in whom an initially successful attempt at endoscopic
      hemostasis fails and who rebleed while hospitalized. Recommendations for the
      surgical management of bleeding peptic ulcer disease include Immediate operation
      for (1) patients with rapidly exsanguinating ulcer hemorrhage and (2) patients
      with active bleeding and failure of endoscopic hemostasis to control the
      bleeding. Early elective operation after initial endoscopic hemostasis for (1)
      elderly patients with comorbid disease and/or hemodynamic instability who have
      active arterial ulcer hemorrhage (Forrest Ia) controlled with endoscopic
      hemostasis; (2) elderly patients with comorbid disease and/or hemodynamic
      instability who have a visible vessel in an ulcer crater (Forrest IIa) treated
      with endoscopic hemostasis: surgery is particularly advised in this circumstance
      for those with a positive arterial Doppler signal in the ulcer crater or a large
      posterior duodenal ulcer or a large lesser-curvature gastric ulcer; and (3)
      elderly patients with comorbid disease and/or hemodynamic instability who develop
      recurrent ulcer bleeding while hospitalized or with a total blood transfusion
      requirement exceeding 5 U.

PMID- 8307642
TI  - Variceal hemorrhage: surgical therapy.
AB  - Surgical options for management of variceal hemorrhage include portosystemic
      shunts (nonselective and selective), nonshunting operations, and hepatic
      transplantation. In most centers, operations that preserve hepatic portal
      perfusion (selective shunt and nonshunting operations) have replaced nonselective
      shunts as the most commonly performed surgical procedures. The results of
      multiple controlled trials suggest that the frequency of postshunt encephalopathy
      is less after the distal splenorenal shunt than after the nonselective shunts.
      Hepatic transplantation should be considered as initial therapy for nonalcoholic
      cirrhotics and abstinent alcoholic cirrhotics with variceal hemorrhage or
      advanced liver disease and without contraindications.

PMID- 8307643
TI  - Less frequent causes of upper gastrointestinal bleeding.
AB  - Although they account for a minority of episodes of upper gastrointestinal
      bleeding, the awareness of less frequent causes of upper gastrointestinal
      bleeding can be crucial to the endoscopist in the evaluation of the patient with
      bleeding. This review discusses the Dieulafoy lesion, hemobilia, gastric antral
      vascular ectasia, Mallory-Weiss tear, and gastroduodenal arteriovenous
      malformation.

PMID- 8307644
TI  - Measurement of aging anxiety: development of the Anxiety about Aging Scale.
AB  - This research is based on the premise that aging anxiety is an important
      mediating factor in attitudes and behavior toward elderly individuals as well as
      a mediating factor in adjustment to one's own aging processes. The combined
      concern and anticipation of losses centered around the aging process constitute
      aging anxiety. This article proposes a multidimensional aging anxiety model,
      develops a measurement of this model, and assesses the factorial validity of the
      model. The original eighty-four item Anxiety about Aging Scale (AAS) was
      developed to assess four dimensions of aging and three types of fears. A
      principal components analysis of data collected from 312 adult volunteers
      revealed the presence of four interpretable factors: 1) Fear of Old People, 2)
      Psychological Concerns, 3) Physical Appearance, and 4) Fear of Loss. Items were
      eliminated to strengthen this factor structure and resulted in the retention of
      twenty items. Men were significantly more anxious about aging than were women on
      the AAS. Correlates of the four factors and implications for further research are
      discussed.

PMID- 8307645
TI  - Changing attitudes toward the old in Oriental families in Israel.
AB  - Old people held a central position in traditional Jewish-Oriental family and
      society. After immigration to Israel this changed within a very short time, as
      Israel's Western-style society is not based upon the authority of the elder
      generation. Often this change was accompanied by the development of negative
      attitudes toward the aged, appearing in many families as disrespect and even as
      physical neglect of parents. But in other families the traditional attitudes of
      honoring the elder generation were retained, although in them too the rise of the
      nuclear family led to loss of power and importance formerly held by the aged
      members. The changing attitudes within the family are reflected in discussions by
      disadvantaged soldiers of Oriental origin in classes for basic training in the
      Israeli army and by answers of fifth-grade children to questions on their
      relations with their grandparents.

PMID- 8307646
TI  - Trends in care and services for elderly individuals in Denmark and Sweden.
AB  - Both Denmark and Sweden have achieved a reduction in institutionalization of
      elderly individuals; 23 percent nursing home care in Denmark from 1980-89 and 34
      percent overall institutionalization in Sweden from 1970-1985. This was
      accomplished by increasing home care and housing with services and adaptations.
      Further increases in growth of the elderly population combined with modest
      economic expansion will be the forces responsible for finding additional
      alternatives to costly institutional care. Community-based services and care have
      not been demonstrated at this time to be less costly than institutional care. An
      illustration of an innovative model of nursing home care in Denmark is described.
      The medical model of care was abandoned in favor of a self-care model for the
      purpose of fostering independent living and decision-making as long as possible.
      In Sweden, a reduction in demand for beds in a long-term care hospital has been
      achieved through a tightly coordinated system of care and services among the
      various health and social service professionals.

PMID- 8307647
TI  - Family network and mortality: survival chances through the lifespan of an entire
      age cohort.
AB  - This study relates certain family network variables (martial status and number of
      children) to chances of survival. Through multivariate analysis, survival is also
      related to social class, social mobility, migration and local environment, and
      legitimacy of birth. All persons in a local birth cohort born in the years 1902
      and 1903 were followed in population records from birth until eighty years of
      age. The group comprised 487 individuals with a dropout rate of 4 percent.
      Univariate survival analysis between twenty to eighty years of age showed widows
      and also divorced women to have a significantly higher survival than those still
      married and never married. Never married men and women had the lowest survival
      rates. The number of children was not associated with survival for neither men
      nor women when controlled for marital status. Multiple regression survival
      analysis showed different patterns for males and females. The risk of not
      surviving to eighty years of age for men resulted from a combination of being
      single, downward social mobility, a father in the manual working class group and
      few children, with being single as the strongest predictor. For women the
      strongest predictor for death before eighty was the category single and/or
      married (as opposed to earlier married). The combination of being single/married,
      high migration, earlier life mainly in rural areas, and having few children were
      predictors in the model of death before eighty. Thus, for both men and women
      marital status was the strongest predictor for survival but in different ways.

PMID- 8307648
TI  - Including social factors in the analysis of reminiscence in elderly individuals.
AB  - Developmental psychologists have studied reminiscence in elderly individuals
      using widely varied conceptions of adult development. Determinist psychologists
      conceived of reminiscent behavior in elderly individuals as constituting the last
      phase in normal development. Contextualist psychologists have pointed to the
      historical and cultural relativity of adult development, and highlighted the
      variation in elderly persons with respect to reminiscent behavior. However, they
      do not fully acknowledge the role the environment plays in establishing
      reminiscent behavior in elderly people. Therefore, sociological life course
      theory should be included in the analyses and interpretation of this behavior.

PMID- 8307649
TI  - Making sense of usefulness: an avenue toward satisfaction in later life.
AB  - Studies of later life assert that sense of usefulness impacts life satisfaction.
      This study determines what impacts sense of usefulness. The sample consists of
      108 older adults, ages sixty through ninety, who were involved with community
      organizations. The research instrument was a forty-five-item questionnaire.
      Findings identify five correlates of sense of usefulness: continuity in respect
      from younger ages (p < .01), involvement with family (p < .05), involvement with
      a significant other (p < .01), involvement with community (p < .01), and meeting
      one's expectations for old age (p < .01). "Continuity in respect," "meeting one's
      expectations," and "sense of usefulness" combine into a scale that correlates
      with satisfaction in later life (p < .001). Results contribute to theoretical
      understanding of later life development and suggest directions for work with the
      aging client system.

PMID- 8307650
TI  - Quantitative estimates for the effects of AIDS public education on HIV
      infections.
AB  - Previous projections of HIV infection have not accounted explicitly for AIDS
      public information. The present analysis does so, using computer content analysis
      of AIDS news stories to make time trend forecasts of both HIV infection and
      knowledge, attitudes, and sexual behaviors relevant to AIDS. The data show that
      there was a rapid rise in infections before public information took effect. Then
      news about AIDS, its modes of transmission and high risk groups led to a 3-4-fold
      decrease in high risk sex among gay/bisexual men by the late 1980s. The result
      was a diminished infection rate saving 580,000 to 1.9 million lives. In more
      recent times, rates of HIV infection are forecast to increase again, although
      slowly, in small part because people are less prudent and in large part because
      the pool of infected individuals has greatly expanded.

PMID- 8307651
TI  - Optimal test strategy in the case of two tests and one disease.
AB  - Decision-making, especially about test performance, is very complex in nature.
      Clinical decision analysis can provide tools for doctors which can be used in
      improving the ordering of laboratory tests. This article describes an approach
      which is relevant for medical practice and easy to understand, with the goal of
      obtaining better decisions rather than optimal solutions. The methodology enables
      a clear understanding of the possibilities and restrictions of test use and needs
      very little calculation. The cornerstone of the methodology is a graphical
      representation, by which the benefits of test use are evaluated. Furthermore, a
      simple algorithm has been developed that can be used to find the optimal solution
      in the case of two tests. In each step decision rules can be used. In a graphical
      representation the effect of combining tests can be easily evaluated. If a test
      combination is chosen one has to decide which sequence is optimal. Finally one
      has to choose between parallel and series testing. The gain in time of the
      parallel procedure (and possible gain in effectiveness of treatment) should be
      compared with the efficiency gain of series testing. The authors conclude that
      the developed methodology is closer to the intuitive decision-making process than
      the traditional decision-making techniques and therefore can be used in order to
      improve the rather intuitive decisions of doctors.

PMID- 8307652
TI  - Power spectrum analysis of the fetal heart rate during noradrenaline infusion and
      acute hypoxemia in the chronic fetal lamb preparation.
AB  - In a chronically instrumented fetal lamb the effect on heart rate variability of
      noradrenaline as well as hypoxemia is studied by the use of power spectral
      analysis. Subsequent to both noradrenaline infusion and hypoxemia the very low
      frequency components of the variability are markedly decreased as compared with
      control conditions. After hypoxemia also a high frequency peak appears in the
      spectrum.

PMID- 8307653
TI  - The polar phase response property of monopolar ECG voltages using a Computer
      Aided Design and Drafting (CAD)-based data acquisition system.
AB  - The present paper discusses a Computer-Aided Design and Drafting (CAD) based data
      acquisition and polar phase response study of the ECG. The scalar ECG does not
      show vector properties although such properties are embedded in it. In the
      present paper the polar phase response property of monopolar chest lead (V1 to
      V6) ECG voltages has been studied. A software tool has been used to evaluate the
      relative phase response of ECG voltages. The data acquisition of monopolar ECG
      records of chest leads V1 to V6 from the chart recorder has been done with the
      help of the AutoCAD application package. The spin harmonic constituents of ECG
      voltages are evaluated at each harmonic plane and the polar phase responses are
      studied at each plane. Some interesting results have been observed in some
      typical cases which are discussed in the paper.

PMID- 8307654
TI  - Extrapolation of incomplete marker tracks by lower rank approximation.
AB  - Motion and deformation of an object such as the heart may be measured by tracking
      optical or radiopaque markers. In the experimental situation markers may fail to
      be detected due to occlusion or lack of contrast. As a result a continuous marker
      track is observed in separated parts, which often cannot be directly identified
      as corresponding to one marker. This paper presents a method of extrapolating a
      partly known track by using information provided by the known track part and the
      available complete tracks of other markers. The extrapolations are obtained by
      iteratively fitting a lower rank matrix to the set of noisy, incomplete marker
      tracks. The performance is evaluated with computer-simulated data and data
      obtained in an animal experiment. In both cases 43% of the available complete
      tracks were made incomplete by removal of track parts varying in length from 3%
      up to 44%. For the simulated data comparison of the extrapolations with true
      signal values results in a root mean square (RMS) error about equal to the noise
      level. For the animal experiment, when comparing the extrapolations with the
      measured values, in images of 256 x 256 pixels, the RMS error was found to be +/-
      0.5 pixel, which is quite small relative to the total excursion of a marker (20
      pixels). Estimation of the missing data by applying BMDPAM (BMDP Statistical
      Software Inc.) to the same data results in RMS errors which are about twice as
      high.

PMID- 8307655
TI  - EndoCyte 1.2: An improved algorithm for quantitative analysis of receptor
      mediated endocytosis.
AB  - This paper reports the improvement of EndoCyte, the computer program for kinetic
      analysis of receptor-mediated endocytosis. A non-standard algorithm for parameter
      evaluation was developed and incorporated into the program. The comparison of the
      original program and the updated EndoCyte 1.2 revealed that the new algorithm was
      significantly more efficient.

PMID- 8307656
TI  - PC program for estimating polynomial growth, velocity and acceleration curves
      when subjects may have missing data.
AB  - A stand-alone, menu-driven PC program, written in GAUSS386i, for estimating
      polynomial growth, velocity, and acceleration curves from longitudinal data is
      described, illustrated and made available to interested readers. Missing data are
      accommodated: we assume that the study is planned so that individuals will have
      common times of measurement, but allow some of the sequences to be incomplete.
      The degrees, Di, adequate to fit the growth profiles of the N individuals are
      determined and the corresponding polynomial regression coefficients are
      calculated and can be saved in ASCII files which may then be imported into a
      statistical computing package for further analysis. Examples of the use of the
      program are provided.

PMID- 8307657
TI  - A rule-based postoperative pain controller: simulation results.
AB  - We describe a system for controlling postoperative pain, a phenomenon that is
      difficult to treat by conventional control methods due to interpatient
      variability, interferences, non-linearity and the lack of a plausible, well
      defined mathematical model. The system consists of two phases. In Phase 1 a
      closed-loop fuzzy controller implementing a suitable control strategy brings the
      patient to a zero-pain state. In Phase 2, an open-loop computer-assisted
      continuous infusion controller maintains a constant concentration of the
      analgesic (alfentanil) in plasma, subject to an upper safety limit on infusion
      rate; the set-point of this controller is periodically revised (either maintained
      or reduced) on the basis of feedback on the duration of zero pain (set-point
      reduction is necessary because the open-loop system has no means of knowing
      whether analgesic is accumulating in the patient). Pain is quantified by the
      patient on a numerical scale of 1 to 10 at 1.5-min intervals during Phase 1 and 9
      min intervals during Phase 2. In simulation trials in which a fixed approximate
      model was used for the effect of sedation on pain while the pharmacokinetics of
      alfentanil were varied from one simulated patient to another, zero pain was
      achieved in under 15 min with minimal overshoot in plasma drug concentration and
      was maintained, with only minor deviation, by means of low drug concentrations.

PMID- 8307658
TI  - Quantitative analysis of dystrophin gene amplification products using a PC-based
      image analysis system.
AB  - A PC-based image analysis system for gel photographs of DNA gel patterns was
      developed. It was originally designed as a general-purpose, low-cost, yet high
      performance system for wide applications in the biomedical area. In this study,
      we performed analysis of gel images obtained by polymerase chain reaction (PCR)
      amplification. The system employs a high-resolution CCD camera that can
      accurately measure grayness of the gel photographs for quantitative analysis of
      PCR products. The target DNA (exon 52 of the dystrophin gene), which had been
      found to be deleted in some patients with Duchenne/Becker muscular dystrophy
      (DMD/BMD), was amplified for the female family members together with the control
      DNA (exon 60) as a reference. The ratio of the target DNA to the control DNA was
      determined from PCR products to identify the carrier status of this disease by
      means of gene dosage. We conclude that 'the PC-based image analysis system' was
      useful for quantitative deletion analysis of DMD/BMD heterozygotes.

PMID- 8307659
TI  - PC program extending the two-stage polynomial growth curve model to allow missing
      data.
AB  - A stand-alone, menu-driven PC program, written in GAUSS386i, extending the
      analysis of one-sample longitudinal data sets satisfying the two-stage polynomial
      growth curve model (Ten Have et al., Am J Hum Biol, 3 (1991) 269-279) to allow
      missing data is described, illustrated and made available to interested readers.
      The method and the program are illustrated using data previously analyzed by the
      authors (Schneiderman and Kowalski, Am J Phys Anthropol, 67 (1985) 323-333) but
      with several randomly chosen data points discarded and treated as missing.

PMID- 8307660
TI  - Parameter sensitivity of a model of viral epidemics simulated with Monte Carlo
      techniques. IV. Parametric ranges and optimization.
AB  - A model is presented of the spread of influenza into and within a nursing home.
      To use this model for studies involving surveillance and vaccine efficacy, it is
      necessary to estimate optimal ranges of a group of parameters. Attempts to do so
      by manual methods proved unsatisfactory. Initial use of the methods presented in
      the previous three papers of this series led to points that were also
      unsatisfactory. However, by noting which parameters were placed at the outer
      surface of the chosen hypervolume, it was possible to choose new ranges and to
      select an optimal point in hyperspace that satisfied the epidemiologically
      preselected characteristics.

PMID- 8307661
TI  - Risk dimensions of HIV-tested substance users.
AB  - Methadone outpatients (n = 177) and outpatients enrolled in a nonchemotherapy (n
      = 65) counseling unit requested HIV testing. A HIV risk-related questionnaire
      elicited information on needle-sharing, drug injecting, sexual behaviors, and
      other risk activities. Although age and geographical seroprevalence were not
      significantly related to a positive HIV test result, a significant relationship
      was found between the patient's self-report of AIDS deaths among personal
      acquaintances and serostatus. Dimensions of risk concerns were found to be
      significantly related to gender in the methadone sample but not in the
      nonchemotherapy sample. Serostatus in the nonchemotherapy sample was
      significantly related to drug injecting and the sum of a 12-item risk index
      constructed to predict HIV infection.

PMID- 8307662
TI  - Beyond liver and culture: a review of theories and research in drinking among
      Chinese in North America.
AB  - Low levels of alcohol consumption and drinking problems have been consistently
      found among the Chinese in North America and in other Chinese societies. Two
      theories of Chinese drinking have been popular in the literature. First, the
      physiological explanation attributes the light alcohol use among the Chinese to
      their high propensity to flush, which protects them from heavy drinking. Second,
      the cultural explanation suggests that Chinese cultural values emphasizing
      moderation and self-restraint discourage drinking to the point of drunkenness. A
      review of existing research shows that both explanations are not supported by
      adequate empirical research findings and are plagued with conceptual and
      methodological shortcomings. It is also noted that both theories cannot explain
      why some Chinese do become heavy or problem drinkers. It is suggested that we
      should look beyond physiological and cultural factors for a better understanding
      of contemporary Chinese drinking patterns.

PMID- 8307663
TI  - Adolescent cigarette consumption: the influence of attitudes and peer drug use.
AB  - Predictors of tobacco consumption were investigated with path analytic techniques
      using household survey data from 1,093 teenagers aged 13-17. When current smokers
      are compared to past or never smokers, pro-tobacco attitudes are always the most
      important predictor variable followed by friends' use of marijuana and own use of
      marijuana, suggesting that pro-tobacco attitudes are responsible for maintaining
      tobacco consumption. We infer that peer illicit drug use has the greatest effect
      in taking up smoking because it is the most important predictor of past smoker
      status compared to never smoking and it does not appear as such an important
      predictor of current use compared to never smoker status. Pro-tobacco attitudes
      are a consequence of smoking rather than an influence upon taking up smoking.

PMID- 8307664
TI  - No consensus on fighting the drug war: differences between state policy elites
      and the mass public.
AB  - This article explores implications for the implementation of drug policy in the
      United States, based on the findings from a 1990 survey of state drug policy
      coordinators in all 50 states and the responses to a national mass public survey.
      State drug policy elites' perceptions of the relative seriousness of nine
      different specific drugs are assessed, together with their evaluations of federal
      drug policy. Significant differences in state elites' attitudes are found for
      certain regional effects, for the relative degree of state urbanism, and for
      relative state income levels. These results are compared against the findings
      from a 1989 CBS News/New York Times mass opinion survey measuring citizen
      perceptions on drug misuse and the efficacy of Bush administration policy
      initiatives. This comparison reveals a wide disparity between elite and mass
      attitudes regarding appropriate funding of the drug war, the rating of federal
      drug policy initiatives, and federal drug policy strategies. Such mass/elite
      perceptual disparities accentuate the difficulties inherent in pursuing a "drug
      war" strategy.

PMID- 8307665
TI  - The role of selected risk factors in predicting adolescent drug use and its
      adverse consequences.
AB  - The purpose of this study was to examine the effectiveness of selected risk
      factors in predicting alcohol and other drug (AOD) use and adverse consequences
      of use. Three regression analyses were performed on four categories of risk
      factors: individual, family related, school related, and social related. The
      sample size was 887 (99%). Significant predictors for AOD use were grade level,
      participation in religious services, GPA, frequency of dating and driving,
      trouble at school, mastery, and family management index. Predictors for adverse
      consequences were GPA, frequency of dating, trouble at school, family management
      index, risk taking, alienation, susceptibility to peer pressure, and living
      arrangements.

PMID- 8307666
TI  - Drug users' self-reports of behaviors and affective states under the influence of
      alcohol.
AB  - This study tested a modified version of the Alcohol-Related Behavior
      Questionnaire (ARBQ) to investigate the influence of alcohol on negative mood
      states. The ARBQ asked subjects (substance users and those not misusing drugs or
      alcohol) to recall various moods and behaviors under three drug conditions:
      sober, drinking, and drunk. Tests of the ARBQ subscales provided support for its
      reliability and validity. Scale scores measuring negative affect increased as
      levels of recalled alcohol intake increased, suggesting that larger amounts of
      alcohol produced more negative and aggressive feelings. Alcohol-dependent
      subjects reported more anger and aggression with increasing levels of alcohol
      intake than nonproblem drinkers. These data further indicated that, among those
      with alcohol dependence, a history of childhood aggression is an important
      predictor of negative behaviors and feelings associated with alcohol intake.
      Among other groups of drug users, a diagnosis of antisocial personality was
      relatively more important.

PMID- 8307667
TI  - Physicians and intravenous drug users: attitudes and opinions in the Canton of
      Vaud, Switzerland.
AB  - A postal questionnaire was used to survey the attitudes of practising physicians
      in the Swiss Canton of Vaud (population 570,000) toward intravenous drug (IVD)
      users and to study the possibility of recruiting more such physicians for
      treatment of these patients. The study population included all general
      practitioners, internal medicine specialists, and psychiatrists in private
      practice in the canton (n = 776). The response rate was 50%. Results indicate
      that it would be possible to significantly increase (40 to 100%) the number of
      practising physicians now treating IVD users.

PMID- 8307668
TI  - Depression as an antecedent of frequency of intravenous drug use in an urban,
      nontreatment sample.
AB  - The present study examined the relationship between depressive symptoms and
      frequency of drug use in 91 low income nontreatment intravenous drug users in
      Baltimore, Maryland. The majority of participants were injecting both heroin and
      cocaine. Scores on the depression scale at both waves were correlated with
      frequency of injection at wave two. Depression at wave one had a higher
      correlation with frequency of injections at wave two than did concurrent
      depression at wave two. Even after accounting for several confounds between
      depression and frequency of injection, depression at wave one remained highly
      correlated with frequency of injection at wave two.

PMID- 8307669
TI  - Gender life expectancy and alcohol: an international perspective.
AB  - This research determined the alcoholism-related and other correlates of the
      discrepancy between life expectancy in females and males using information for
      161 different countries. The variables that correlated most highly with female
      minus male life expectancy were per capita alcohol consumption, cirrhosis of the
      liver deaths per capita, and overall life expectancy. Greater gender discrepancy
      was also found in non-Moslem countries and in countries with greater per capita
      income and less infant mortality. Public health implications are discussed.

PMID- 8307670
TI  - Mortality and use of health services surveys in rural Zaire.
AB  - The Combatting Childhood Communicable Disease (CCCD) project is a comprehensive
      public health programme designed to reduce child mortality by 25% through the use
      of the following strategies: vaccination, oral rehydration therapy, and prompt
      treatment for malaria. To evaluate this programme, cross-sectional surveys were
      conducted in neighbouring health zones in Zaire in 1984 to determine the use of
      selected medical services by the population and to estimate the child mortality
      rate before the CCCD programme began. A reinterview survey was conducted on a
      subsample of women previously interviewed to determine the reliability of the
      mortality estimates. In both health zones 84-85% of women used antenatal
      services, 45% of children under age 6 who had had fewer were treated with an anti
      malarial drug, 19-22% of children age 12-23 months had been vaccinated against
      measles, and virtually no children who had had diarrhoea were treated with oral
      rehydration therapy. Women's underreporting of births and deaths resulted in low
      estimates of mortality in both surveys. The reinterview survey provided more
      accurate estimates of mortality and led to a better understanding of the factors
      influencing underreporting. The estimated infant mortality rate was 74 deaths per
      1000 livebirths; and the probability of dying before age 5 was 191 per 1000.
      Because births and deaths reported with incomplete dates were excluded from
      analysis, the mortality rates from the reinterview survey are underestimates.
      Given the difficulty in obtaining accurate estimates of mortality, primary
      importance should be given to developing and improving routine health information
      systems that measure changes in health status and provide information to evaluate
      programmes.

PMID- 8307671
TI  - Monitoring child survival programmes in Africa: the Africa Child Survival
      Initiative. Background.

PMID- 8307672
TI  - Changes in use of health services in a rural health zone in Zaire.
AB  - As part of the Combatting Childhood Communicable Diseases (CCCD) project funded
      by the US Agency for International Development (USAID), the Zairian CCCD
      programme conducted surveys in the rural health zones of Kingandu and Pai
      Kongila, Zaire, in 1984-1985 and 1988-1989 to determine whether a strategy of
      selective primary health care would affect childhood mortality. This paper
      describes the changes in the medical care infrastructure and the increasing
      coverage of selected services. The strategies evaluated were vaccination, oral
      rehydration therapy, and treatment of febrile episodes with antimalarial drugs
      for children; and tetanus vaccination and malaria prophylaxis for pregnant women.
      The health infrastructure in the Kingandu and Pai-Kongila Health Zones expanded
      considerably from 1984 to 1989, with health centres increasing from 7 to 18.
      During this period, economic conditions deteriorated moderately, with the nation
      experiencing nearly 700% inflation. Medical care costs remained stable because of
      external subsidies. Use of health services was assessed in 1984, 1988, and 1989.
      Between 1984 and 1989, the proportion of children aged 12-23 months vaccinated
      against measles increased from 22% to 71%. Coverage with other vaccine antigens
      increased similarly. Women's knowledge of the correct recipe for the preparation
      of sugar-salt solution increased from 0% to 61%. Reported treatment at home with
      sugar-salt or oral rehydration solution increased from 6% to 53%. The proportion
      of children with febrile episodes who were treated presumptively for malaria with
      chloroquine remained unchanged (47% in 1984; 44% in 1988). We conclude that,
      despite a moderate deterioration in economic conditions, Kingandu and Pai-Kongila
      Health Zones achieved remarkable increases in use of selected health services
      between 1984 and 1989, especially in vaccination coverage.

PMID- 8307673
TI  - Impact of selective primary care on childhood mortality in a rural health zone of
      Zaire.
AB  - Following the introduction of intensified child survival activities, use of
      health services for children increased markedly: measles vaccination reached 74%
      of children aged 12-23 months, and the use of oral rehydration therapy for the
      treatment of diarrhoea had increased. During the same period, childhood mortality
      declined by 33% for children aged 1-4 years. Data on cases of measles in the
      local hospital reveals that the pattern of measles epidemics characteristic of
      the years preceding programme implementation was altered in the years following
      programme implementation. The mean annual number of inpatient measles cases
      declined from 108 before the programme to 36 after its start. The high
      correlation between the number of inpatient measles cases and mortality at ages 6
      35 months suggests that the programme reduced mortality largely by reducing the
      incidence of measles. Primary health care activities, supported in part by the
      Combatting Childhood Communicable Diseases Project, is estimated to have reduced
      mortality at ages 6-35 months by at least the 18-23% associated with the change
      in the incidence of measles and may have been responsible for the full 28%
      reduction recorded between 1980-1984 and 1985-1989.

PMID- 8307674
TI  - Infant and child mortality estimates in two counties of Liberia: 1984.
AB  - To estimate baseline infant and child mortality in Liberia, a survey was carried
      out in 1984 as part of the Combatting Childhood Communicable Diseases (CCCD)
      project. The project, a collaborative effort of the Liberian Ministry of Health,
      the US Agency for International Development, and the US Centers for Disease
      Control, is aimed at reducing childhood morbidity and mortality through oral
      rehydration therapy, vaccination and treatment for malaria. As a measure of
      programme impact, mortality estimates from this survey will be compared with
      those from a second survey after 4-5 years. A sample of 40 clusters (50-70
      households per cluster) was used. The size is sufficient to detect a 25%
      reduction in mortality of children under 5 years of age. Mortality was estimated
      from a pregnancy history questionnaire asked of women aged 15-49 residing in
      cluster households. A reliability survey was conducted and pregnancies were
      matched to determine the level of omission of births and deaths. Results show a
      very high level of mortality with a risk of death in infancy above 20% and a risk
      of dying before the fifth birthday of one-third. Since the extent of omission of
      deaths in the first survey proved substantial, the reinterview survey was
      essential.

PMID- 8307675
TI  - Immunization, oral rehydration therapy and malaria chemotherapy among children
      under 5 in Bomi and Grand Cape Mount counties, Liberia, 1984 and 1988.
AB  - As part of an evaluation of child survival programmes in 13 African countries,
      cluster surveys were carried out in two Liberian counties in 1984 and 1988 to
      measure use of three primary health care services: immunization of infants,
      antimalarial treatment of children with fever, and oral rehydration of childhood
      diarrhoea. Immunization rates increased (30-53% for DPT-1 and 13-33% for
      measles), treatment of malaria with drugs available in the home increased from 5
      to 35%, and home use of sugar-salt solution to prevent dehydration remained
      essentially unchanged, 5.9% in 1984 and 3.8% in 1988.

PMID- 8307676
TI  - Infant and child mortality in two counties of Liberia: results of a survey in
      1988 and trends since 1984.
AB  - A baseline survey of childhood mortality in two counties of Liberia in 1984 found
      the risk of dying before age 5 to be almost one-third. Three years into the
      Combatting Childhood Communicable Diseases (CCCD) project, a survey using a
      pregnancy history questionnaire was conducted in the same clusters to determine
      if any change in mortality had occurred. Reinterviews were done in a subsample
      and pregnancies were matched from the two surveys to determine levels of missing
      events. After adjustment for omission, infant mortality was estimated at 180 per
      1000, a 25% decline from the estimated 1984 level. Childhood mortality declined
      by an estimated 28%. Tabulations of death by reported cause using a verbal
      autopsy questionnaire showed that the risks of neonatal tetanus and fever
      associated deaths declined significantly. These reductions might have been a
      direct result of programme activities which were shown by a marked increase in
      tetanus toxoid immunization and access to antimalarial drugs in the study area.

PMID- 8307677
TI  - Impact of health programmes on child mortality in Africa: evidence from Zaire and
      Liberia.
AB  - The Mortality and Use of Health Services studies were designed to measure changes
      in the coverage of health services and in infant and child mortality rates
      associated with the implementation of the Combatting Childhood Communicable
      Diseases programme. The papers in this supplement provide the results of research
      carried out in areas of Zaire and Liberia. Data from these studies provide
      credible evidence that these programmes actually reduced mortality. The
      proportion of children dying by their fifth birthday declined by 17% in Zaire and
      by 32% in Liberia. These estimates of programme impact are consistent with the
      increases in the use of health services and with data from similar studies in
      other countries. Results of these surveys suggest that child survival programmes
      in Africa can reduce mortality substantially in populations living in different
      environments at very different initial levels of child mortality.

PMID- 8307678
TI  - A critical analysis of the design, results and implications of the Mortality and
      Use of Health Services surveys.

PMID- 8307679
TI  - A strategy for evaluating the mortality impact of child survival programmes in
      Africa: Combatting Childhood Communicable Diseases Project.
AB  - The Mortality and Use of Health Services surveys were designed to measure the
      mortality impact of the Combatting Childhood Communicable Diseases programmes
      which are based on childhood vaccinations, prenatal immunization against tetanus,
      home-based use of oral rehydration therapy, and presumptive treatment of malaria.
      The survey design includes pretest and post-test surveys in programme and non
      programme areas. The questionnaires are designed to collect information on use of
      health services and on pregnancy histories to provide retrospective reporting of
      child mortality. When combined with data from surveillance systems (particularly
      information on cases of measles cases seen at clinics and health centres), these
      data should provide reasonable estimates of programme impact.

PMID- 8307680
TI  - Effect of secondary structure on the rate of deamidation of several growth
      hormone releasing factor analogs.
AB  - The objective of this study was to determine whether the rates of deamidation of
      Asn8 in selected growth hormone releasing factor (GRF) analogs were related to
      the peptide's secondary structures in solution. Bovine or human [Leu27]GRF(1
      32)NH2 (both having Gly at position 15), [Ala15Leu27]bGRF(1-32)NH2 and
      [Pro15Leu27]bGRF(1-32)NH2 were used as model peptides. The peptide helical
      content (assessed by CD) increased with the increasing methanol concentration and
      was as follows: 7, 12 and 18% in 0% MeOH; 24, 48 and 52% in 40% MeOH; and 41, 77
      and 81% in 80% MeOH for Pro15Leu27 bGRF(1-32)NH2, [Leu27]hGRF(1-32)NH2 and
      Ala15Leu27 bGRF(1-32)NH2, respectively. 2D NMR studies done in the presence of
      40% CD3OH indicated more helical structure for the Ala15 analog as compared to
      [Leu27]hGRF(1-32)NH2. In both these peptides Asn8 was included in the helical
      region. In contrast, the lack of conformational information for the Pro15 analog
      indicated little helical structure around Asn8. The peptides' deamidation rates
      decreased and their half-lives increased with increasing MeOH concentrations. At
      40% MeOH, the least helical Pro15 bGRF analog (t1/2 = 10.78 h) deamidated 1.5 and
      2 times faster than its Gly15 (t1/2 = 15.74 h) and Ala15 (t1/2 = 21.53 h)
      counterparts, respectively. This study indicates that helical environment around
      Asn8 in GRF makes this residue less prone to deamidation.

PMID- 8307681
TI  - Importance of lysine and arginine residues to the biological activity of
      trichosanthin, a ribosome-inactivating protein from Trichosanthes kirilowii
      tubers.
AB  - Lysine and arginine residues in trichosanthin were modified with ethyl
      acetimidate and phenylglyoxal, respectively. The effects of these chemical
      modifications on the cell-free protein-synthesis-inhibitory activity and the
      antigen-antibody (Ag-Ab) interaction between trichosanthin and its antibody were
      examined. Ethyl acetimidate modification abolished the protein-synthesis
      inhibitory activity of trichosanthin. The inactivation process followed simple
      first-order kinetics with an inactivation half-life of about 18.5 min.
      Modification of one lysine residue seemed to be responsible for such
      inactivation. Arginine modification also inactivated trichosanthin. The
      inactivation process, however, was biphasic with inactivation half-lives of
      approximately 15 and 540 min. Arginine modification of trichosanthin had little
      or no effect on Ag-Ab interaction, whereas lysine modification slightly but
      significantly weakened Ag-Ab binding.

PMID- 8307682
TI  - Design and synthesis of sulfur-free cyclic hexapeptides which contain the RGD
      sequence and bind to the fibrinogen GP IIb/IIIa receptor. A conformation-based
      correlation between propensity for imide formation and receptor affinity.
AB  - The Arg-Gly-Asp (RGD) sequence is the key recognition site in many adhesive
      interactions. To probe the structural and conformational requirements for
      potential antithrombotic agents, we have designed and synthesized three cyclic
      hexapeptides (1, 5 and 6) containing the RGD sequence. In the ELISA GP IIb/IIIa
      fibrinogen receptor assay, 1, 5 and 6 bound with IC50 values of 1, 0.1 and 0.016
      microM, respectively. All three peptides completely displaced fibrinogen from the
      receptor. No potent, sulfur-free cyclic hexapeptide had heretofore been described
      as a fibrinogen receptor antagonist. The enhanced binding affinity of 6,
      distinguished by the presence of two D-amino acids, is likely to reflect an
      increased conformational resemblance to the natural peptide ligands. Cyclization
      of H-Asp(OFm)-DSer-Phe-DPhe-Arg-Gly-OH with DPPA and NaHCO3 in DMF to afford 6
      was attended by subsequent aspartimide formation with generation of 9
      fluorenylmethanol. Interestingly, imide formation was not observed with any of
      the three linear hexapeptides (3, 8 and 9), with the all-L-cyclic peptide 1, nor
      with 5, which contains only Ser-1 in the D-configuration. The observed imide
      formation led us to use catalytic transfer hydrogenation rather than piperidine
      to remove the 9-fluorenylmethyl ester protecting group at the beta-carbonyl of
      aspartic acid. Further investigation revealed that imide formation was minimized
      by careful exclusion of water, reducing dissolution of NaHCO3. Thus the
      distinguishing conformational features of 6 express themselves both in receptor
      affinity and chemical propensity toward imide formation.

PMID- 8307683
TI  - Conformational study on trans- and cis-N-acetyl-N'-methylamides of Pro-Xaa
      dipeptides.
AB  - Conformational free energy calculations using an empirical potential (ECEPP/2)
      and the hydration shell model were carried out on the N-acetyl-N'-methylamides of
      Pro-Xaa dipeptides (Xaa = Ala, Leu, Val, Gly, Cys, Met, Phe, Tyr, Asn, Asp, and
      Ser) with trans and cis peptide bonds preceding proline residue in the unhydrated
      and hydrated states. As compared with the results obtained by using the earlier
      version of ECEPP, the values of beta-bend probabilities are doubled. The average
      calculated population of cis-dipeptide is about 4%, which is close to the
      abundance obtained from the analysis of X-ray crystal structures of proteins. The
      beta-bends are the most dominant structures of cis-dipeptides. Type I, usually
      having intramolecular hydrogen bonds, contributes greatly to the beta-bend
      conformations of trans- and cis-dipeptides. However, type I beta-bends of cis
      dipeptides do not have any hydrogen bonds. By including the hydration, the beta
      bend probabilities for trans- and cis-dipeptides decreased, indicating that the
      interactions of water molecules with a backbone or side-chain may force the
      dipeptides to be more distorted or extended. In particular, type II is found to
      be a dominant beta-bend conformation of trans- and cis-Pro-Gly dipeptides in both
      the unhydrated and hydrated states. In general, the calculated propensities for
      Pro-Xaa dipeptides to adopt beta-bend conformations are reasonably consistent
      with available experimental data. From comparing conformations of Pro and Xaa
      residues in the dipeptides and single residues, we found that inter-residue
      interactions and hydration are of importance in determining the conformational
      properties of the Pro-Xaa dipeptide.

PMID- 8307684
TI  - Is an amphiphilic region responsible for the haemolytic activity of Bacillus
      thuringiensis toxin?
AB  - The amino acid sequence of the 27 kDa protein responsible for the haemolytic
      activity of Bacillus thuringiensis subsp. israelensis toxin has been analysed by
      secondary structure prediction, helical wheel/net diagrams and molecular
      mechanics calculations. We found that segment 116-126 presumably forms a strongly
      amphiphilic alpha-helix. This is supported by the findings that the synthesized
      segment 116-126 (a) has a significant alpha-helical content in water, and (b)
      displays an in vitro haemolytic activity comparable to that of bee venom peptide
      melittin. As segment 116-126 is present in the haemolyzing, but not present in
      the non-haemolyzing proteins from B. thuringiensis toxins, we suggest that this
      segment is responsible for the lytic potential of the B. thuringiensis subsp.
      israelensis protein.

PMID- 8307685
TI  - Synthesis of gamma-carboxyglutamic acid-containing peptides by the Boc strategy.
AB  - gamma-Carboxyglutamic acid (Gla) derivatives having several protecting groups at
      the gamma-carboxyl function were synthesized and examined for their stabilities
      and removabilities under the conditions used in peptide synthesis by the Boc
      strategy. Among them, the cyclohexyl (cHx) group of the Gla residue was found to
      be stable during the synthesis of the protected peptides, but was quantitatively
      cleaved by the final HF treatment without decarboxylation. Using Boc-Gla(OcHx)2
      OH as a starting material, the synthesis of Gla-containing peptides was achieved
      by the Boc strategy using a standard HF procedure for the final deprotection.

PMID- 8307687
TI  - Kinetic characterization of alkaline mesentericopeptidase. Comparison with serine
      proteinases from different origins.
AB  - Comparative studies of the hydrolysis of succinyl-Ala2-Phe-methylcoumarylamide
      with mesentericopeptidase, a mesophilic extracellular serine proteinase from
      Bacillus mesentericus, and proteinases produced by organisms representing
      different levels of evolutionary development, were performed. Drastic differences
      in the proteolytic coefficient kcat/Km were found. As regards their catalytic
      efficiency, the proteinases studied can be placed in the following order:
      mesentericopeptidase < subtilisin Novo << subtilisin DY < proteinase K <
      subtilisin Carlsberg < thermitase < alpha-chymotrypsin. The size of the substrate
      binding site of mesentericopeptidase for synthetic peptides was studied by using
      chloromethyl ketones with the general formula benzyloxycarbonyl-Alan-Phe-CH2Cl (n
      = 1, 2, 3). The presence of at least five binding subsites (S1 ... S5) on the S
      side of the hydrolysed bond was suggested. Studies of the primary specificity of
      mesentericopeptidase with a series of dipeptide chloromethyl ketones having the
      general formula benzyloxycarbonyl-Ala-Aa-CH2Cl (Aa = Ala, Val, Leu, Phe) revealed
      the following order of reactivity toward these inhibitors: Aa = Leu >> Ala > Phe
      > Val. Kinetically, mesentericopeptidase is similar to subtilisin BPN'/Novo.

PMID- 8307686
TI  - Molecular structures of two crystalline forms of the cyclic heptapeptide
      antibiotic ternatin, cyclo[-beta-OH-D-Leu-D-Ile-(NMe)Ala-(NMe)Leu-Leu-(NMe)Ala-D
      (NMe)Ala-].
AB  - The crystal structures of two solvated forms of ternatin, cyclo[-beta-OH-D-Leu-D
      Ile-(NMe)Ala-(NMe)Leu-Leu-(NMe)Ala-D-(NMe)Ala-] are reported. The first
      crystallizes with two molecules of peptide and one of dioxane in the asymmetric
      unit: P2(1)2(1)2(1), a = 11.563(1), b = 21.863(2), c = 36.330(4) A. The second
      crystallizes with two molecules of peptide and one of water in the asymmetric
      unit: P2(1)2(1)2(1), a = 14.067(2), b = 16.695(1), c = 36.824(6) A. N-Methylation
      of four of the seven residues of ternatin appears to reduce the number of low
      energy conformations the molecule can assume. The same H-bonded macrocyclic ring
      conformation is adopted by the backbone of each of the four molecules observed
      here. All the amino-acid side chains, with the exception of D-Ile2, have similar
      orientations in each of the four conformers. The heptapeptide macrocycle is
      characterized by: (i) a cis peptide between (NMe)Ala3 and (NMe)Leu4, (ii) a type
      II beta-bend, involving residues Leu5-(NMe)Ala6-D-(NMe)Ala7-beta-OH-D-Leu1,
      stabilized by two H-bonds, N1-->O5 and N5-->O1, between Leu5 and beta-OH-D-Leu1
      residues, (iii) a third intramolecular H-bond, observed in each of the four
      molecules, between the hydroxyl group of beta-OH-D-Leu1 and the carbonyl oxygen
      of D-Ile2.

PMID- 8307688
TI  - Infrared analysis of peptide succinimide derivatives.
AB  - In order to establish parameters to identify imide derivatives formed during in
      vitro aging of aspartyl-alanyl-containing proteins, a dipeptide and a
      tetrapeptide containing this sequence were acidified and heated in vacuo. The
      formation of succinimide derivatives could be confirmed by FTIR and Raman
      spectroscopy. Hereto, earlier assignments of succinimide vibrations had to be
      revised. FTIR absorbance spectra of the succinimide, derived from H-Asp-Ala-OH,
      in the solid state give five bands between 1700 and 1800 cm-1. In this case,
      owing to Fermi resonance, the anti-symmetric imide carbonyl stretching vibration
      gives rise to an apparent doublet, centered around 1715 cm-1. The symmetric
      stretching mode is found at 1793 cm-1. The other bands are assigned to carboxylic
      acid stretching modes (1728 cm-1; COOH dimer and 1751 cm-1: COOH monomer). Fermi
      resonance does not occur in succinimide derivatives occurring in larger peptides.
      As a consequence, the imide bands of the succinimide, generated from H-Val-Asp
      Ala-Gly-OH, are observed at 1716 and 1791 cm-1 (anti-symmetric and symmetric
      stretching modes, respectively).

PMID- 8307689
TI  - Implications of replacing peptide bonds in the COOH-terminal B chain domain of
      insulin by the psi (CH2-NH) linker.
AB  - To evaluate more thoroughly the importance of main-chain structure and
      flexibility in ligand interactions with the insulin receptor, we undertook to
      synthesize analogues with reduced peptide bonds in the COOH-terminal B chain
      domain of the hormone (a stable, but adjustable beta-strand region). By use of
      solid-phase, solution-phase and semisynthetic methods, analogues were prepared in
      which ArgB22 of des-octapeptide(B23-B30)-insulin was extended by the sequences
      Gly-Phe-psi (CH2-NH)-Phe-NH2, Gly-Gly-psi(CH2-NH)-Phe-Phe-NH2, Gly-Phe-psi (CH2
      NH)-Phe-Phe-Thr-Pro-Ala-Thr-OH, and Gly-Phe-Phe-psi (CH2-NH)-Phe-Thr-Pro-Ala-Thr
      OH, and were studied with respect to their abilities both to interact with the
      hepatocyte insulin receptor and to form soluble anion-stabilized hexamers in the
      presence of Co2+ and phenol. Additional analogues of des-pentapeptide(B26-B30)
      insulin were also examined. Overall, our results show that, whereas all analogues
      retain considerable ability to form organized metal ion-coordinated complexes in
      solution, the reduction of peptide bonds both proximal and distal to the critical
      side chain of PheB25 results in analogues with severely diminished receptor
      binding potency. We conclude that the peptide carbonyls from both PheB24 and
      PheB25 are important for insulin-receptor interactions and that the structural
      organization of the region when insulin is bound to its receptor differs from
      that occurring during simple monomer-monomer and higher-order interactions of the
      hormone.

PMID- 8307690
TI  - Teaching and learning in an analytic mode--a model for studying psychoanalysis at
      university.
AB  - The neglected issue of teaching psychoanalysis to non-practitioners, specifically
      in the university setting, is addressed and a model is put forward, which
      recognises the many difficulties that are inevitable to such an undertaking.
      Evolved in the course of two decades of teaching psychoanalysis at the
      university, the model is based on the recognition of certain essential parallels,
      alongside evident differences, between the teaching and learning of
      psychoanalysis and the analytic process itself. As in analysis, the inevitable
      difficulties encountered in the teaching-learning process are treated in this
      model as integral to the process rather than as interfering with it. The analyst
      teaching psychoanalysis in accord with the model uses his/her skills to create an
      atmosphere in which the analytic stance is pervasive, which encourages the
      student to learn in an experientially-near way. Major features of the model are
      discussed, and ways of examining, evaluating and refining it put forward.

PMID- 8307691
TI  - Tangled patterns: Freud, Vienna, and the brain.
AB  - A pattern that prevails in Freud's early texts and carries over into his life
      suggests a culturally-derived coherence in Freud's thinking and work. This
      pattern connects the early studies in neuro-anatomy, the description in Studies
      on Hysteria of the structure of hysterical neuroses, urban design in Vienna,
      antisemitism, and the role of bourgeois values in Freud's life. The theoretical
      basis for this view depends upon the work of cognitive psychologists who define
      thinking as pattern recognition. I propose that consideration of such features as
      the structure of physical space can lend additional dimensions to our
      understanding of Freud, and that a complex appreciation might include attention
      to recent interdisciplinary developments such as chaos theory, and lead to a
      redefinition of the notion of 'cultural context'.

PMID- 8307692
TI  - Freud's cases: are they valuable today?
AB  - To appreciate the recent debate as to whether Freud's case histories should still
      be taught to analysts, it is fruitful first of all to look at the wider context
      of other disciplines. Indeed, there is a contemporary movement at large which
      challenges the notion of canon or any authoritative list of classics. Three
      attitudes towards teaching Freud's works are worth spelling out. There is, first,
      the dismissive attitude represented recently by Jacob Arlow. A second approach is
      that Freud's works should be retained in the teaching curriculum merely for the
      purpose of subverting them. A final approach is that, in spite of the undeniable
      advances in theoretical and clinical psychoanalysis, Freud's case histories
      remain indispensable and even unsurpassed.

PMID- 8307693
TI  - The dynamics of psychoanalytic therapies of the early parent-child relationship.
AB  - This paper examines the psychodynamic factors whereby the conflict of interaction
      in therapies of the early parent-child relationship can be unblocked. The author
      suggests that the therapeutic effect is due to a 'staging' of the conflict by the
      child himself in the form of a dramatic performance. By making his presence felt
      at a precise and meaningful moment while the parents are giving their account of
      the situation, the child makes the interactional conflict manifest and allows the
      therapist to decode the message, to elaborate the emotions projected into him and
      to interpret the unconscious motivations of the various members of the cast of
      the 'play'.

PMID- 8307694
TI  - Sado-masochism in Charlotte Bronte's Jane Eyre: a ridge of lighted health.
AB  - Charlotte Bronte's Jane Eyre contains a paradox of character: Jane Eyre is an
      assertive successful woman, who marries, after every obstacle is overcome, the
      man she loves; she is also a traumatised, terrorised child, who later becomes
      deeply involved, to the point of losing herself, with a moral sadist. In the
      critical literature on Jane Eyre there is controversy concerning Bronte's aims in
      the characterisation of her fictional autobiographer. Did Bronte's artistic
      control of character slip and result in Jane Eyre's irreconciliable attributes?
      Did she mean to give us an assertive feminine heroine and instead reveal her own
      castration complex in the marriage to a maimed and near-blind man? The hypothesis
      of this paper is that the multiple functions of masochism--adaptive, defensive
      and gratifying--the multiple defence mechanisms at work in masochism--denial,
      introjection and projection--and the special layering of masochism at each
      developmental level--oral, anal, and phallic--are mirrored in Bronte's
      characterisation. The irreducible complexity of the clinical concept of masochism
      finds its match in Bronte's characterisation of Jane Eyre.

PMID- 8307695
TI  - Truth and reality in psychoanalytic discourse.

PMID- 8307696
TI  - What is psychoanalysis now?
AB  - Firstly, Freud's classical statement that every treatment that takes into account
      the phenomena of transference and resistance deserves the designation
      psychoanalysis is critically examined in a current, post-classical context. The
      confusion as a consequence of the fact that two different concepts of
      transference are often used indiscriminately is elucidated. Likewise, the dynamic
      conditions of two types of resistance--the classical type, as a result of
      internal conflict, and the interactional type, having to do with empathic failure
      and countertransference--are disentangled and related to current ideas on two
      types of conflict, convergent and divergent. This is technically reflected in the
      understanding of two types of therapeutic action: a nonverbal, object-relational
      factor as distinguishable from the effect of insight and interpretation. Finally,
      the dialectics of insight and relation are theoretically clarified through the
      clinical concepts of background and foreground, which are clinically bound to the
      concrete psychoanalytical situation and form a tool to distinguish the two types
      of transference, resistance and conflict.

PMID- 8307697
TI  - The uniqueness of the patient-analyst pair: approaches for elucidating the
      analyst's role.
AB  - This paper describes ways in which patient-analyst interactions result in a
      unique creation in each psychoanalytic endeavour. The particular character of the
      analyst and analysand overlap in a manner that potentially influences both the
      depth and the limits of the analysis. Analysts, therefore, need to be alert to
      their impact on the analytic process. Three approaches for elucidating the
      analyst's role and its effect on the patient are described. Case examples
      illustrate the impeding effect of unrecognised similarities between patients and
      analysts. Once the analysts became aware of these similarities, there was a
      change in their behaviour, resulting in a deepening and expanding of the
      patients' analytic experiences.

PMID- 8307698
TI  - 'Between the devil and the deep blue sea': the dyad and the triad in
      psychoanalytic thought.
AB  - This paper examines the limitations of the dyad as the prevailing conceptual
      model in psychoanalytic theory and clinical practice, and proposes the triad as a
      more relevant model. From an ontological perspective, triangulation is regarded
      as essential in the development of self-experience in psychic space. The Oedipus
      complex is visualised as a culminating event in a continuum of triadic experience
      rather than as the singular gravitational centerpiece of development. The role of
      the triad and triangulation in child development and clinical technique is
      discussed, with the phenomenon of 'tracking' selected to illustrate the
      limitations of an exclusively dyadic clinical focus.

PMID- 8307699
TI  - The impasse within a theory of the analytic field: possible vertices of
      observation.
AB  - The author attempts to place the problem of the impasse within field theory,
      showing that a prolonged period of countertransference metabolisation is
      sometimes necessary before an analytic process seemingly at a standstill can get
      under way again. Clinical examples are given to demonstrate the emotional
      difficulties with which the analyst must come to grips. The microprocess of the
      session and change in the analyst's mind are considered to be the significant
      loci of any possible resumption of therapeutic progress, provided that hope and
      patience do not fail, and subject also to the ability to adopt new and original
      viewpoints in the session.

PMID- 8307700
TI  - Depression and moral masochism.
AB  - Depression and moral masochism are inseparable, and originate in a particular
      climate of lived experience in which one or both parents suffer from a
      masochistic-depressive disposition. Developmentally, there has been a deficit in
      the child's experience of shared pleasure, and of being a source of enjoyment to
      the parent. Instead, the child experiences himself or herself as a source of pain
      and feels responsible for the parent's dysphoric, anhedonic state. This is not
      simply a fantasy construction of the child, as parental reproachfulness is
      characteristically encountered. The child makes reparative efforts, but they
      generally do not succeed. Central psychological capacities are compromised under
      these conditions, particularly a sense of personal efficacy and of natural
      entitlement. The evolution of initiative, autonomy, and individuation are also
      significantly affected. The aggression, both conscious and unconscious, which is
      generated by these early conditions creates intrapsychic conflict which further
      inhibits the development of these essential psychological functions. Some
      therapeutic recommendations are proposed based on these considerations.

PMID- 8307702
TI  - Some reflections on humour in psychoanalysis.
AB  - This article proposes that for humour to be effective as a therapeutic
      intervention in psychoanalytic treatment, it must approximate an affect releasing
      and growth promoting interpretation. The presence and psychological significance
      of surprise, which is common to both wit and 'good' interpretations, is taken as
      the point of departure and the importance of the psychoanalyst's spontaneity is
      discussed in relation to this. The author explains his opposition to the use of
      humour as a contrived communication: as a parameter aimed at reviving a dying
      analysis or as an attempt to resolve an impasse. In particular the dangers of
      countertransference acting out the provision of transference gratifications are
      explored. Equal emphasis is placed on recommending that the analysis of a
      patient's humorous responses should not be neglected and how an analyst without
      humour may negatively affect the treatment process. The paper includes clinical
      vignettes which illustrate the constructive and creative use of humour in the
      analytic situation.

PMID- 8307701
TI  - The absent father: his role in sexual deviations and in transference.
AB  - In this paper, sexual perversion is discussed and connected with the absence of
      the father and with the failure of a primary relationship with a mother who is
      incapable of leading the child to the threshold of Oedipus. Sexual perversion may
      be considered as the expression of a narcissistic personality organisation which
      makes massive use of splitting and projective identification as a defence against
      separation anxiety. This prevents homosexual perverts from dis-identifying from
      their mothers and from attaining a distinct gender identity. The clinical case of
      a homosexual male patient is presented, where the absence of the father underlay
      his resentment, conveyed in the transference by means of lamentations and
      boredom, with which the patient sadistically tormented the analyst, thus giving
      vent to his deep resentment over an absent and unreliable father and over a
      mother from whom he could only be separated at the cost of persecutory anxiety
      and feelings of jealousy.

PMID- 8307703
TI  - A phantasy of infection.
AB  - 'A phantasy of infection' is a case study of the role of unconscious phantasy in
      the experience of illness. This paper discusses a phantasy that was brought to
      light during the psychoanalysis of a homosexual man who has been diagnosed as HIV
      positive. The paper concentrates on the difference between this patient's
      conscious knowledge of his infection and an unconscious phantasy which was
      reawakened and elaborated in this situation. Detailed clinical material is
      presented to illustrate the point that the often unexpected and strange relation
      the patient has to his infection can be explained only through an understanding
      of such unconscious phantasies as they are lived-out and analysed in the
      transference.

PMID- 8307704
TI  - Conditions for the relevance of infant research to clinical psychoanalysis.
AB  - There is increased pluralism within psychoanalysis today, and the practice of
      psychoanalysis rests on many different theories and distinctly different
      epistemologic perspectives about the nature of the truth, the position of the
      observer-analyst in the process, and the phenomena to be observed. The relevance
      of developmental observation research to clinical psychoanalysis will vary with
      the epistemological perspective of the practitioner, and to be relevant the
      perspective of the researcher must 'match' that of the clinician. Additionally,
      its relevance is conditioned by what is considered 'empirical' data, i.e. whether
      the data are defined behaviourally or by empathic judgements of an observer.
      Three broad categories of psychoanalytic perspectives are discussed: empirical
      natural science, hermeneutic-empirical, and hermeneutic-constructivist. A patient
      in analysis is described, with details of two sessions. Three imaginary
      consultants, each representing one of the major epistemological clinical
      perspectives, comment on the material to demonstrate the relationship among
      technique, epistemology, and the ways infants and developmental observation
      research may be relevant (or not relevant).

PMID- 8307705
TI  - A candidate dreams of her patient: a report and some observations on the
      supervisory process.
AB  - In this paper we argue that a candidate's reporting of her countertransference
      dream (CTD) in supervision, and its subsequent discussion, had two consequences.
      Firstly, it enabled the candidate to find her way out of an acute therapeutic
      impasse with her patient. Secondly, it provided important experimental and
      cognitive learning for the candidate, especially in the area of
      countertransference management and in the maintenance of her analytic work ego.
      This successful use of her CTD allowed her to enhance her self-analytical skills,
      with particular reference to her ability to monitor her own affective responses,
      and subsequent interpretive formulations, to her patient's contributions to the
      on-going transference-countertransference dynamic. Our findings concur with those
      of other authors who suggest that CTDs occur at conflict-laden times in analysis.
      In addition, we postulate a link between the parallelism phenomenon and CTDs as
      adaptive responses to internal and external challenges in the context of control
      analyses and supervision.

PMID- 8307706
TI  - Biological zero of laser Doppler fluxmetry: microcirculatory correlates in the
      hamster cheek pouch during flow and no flow conditions.
AB  - The microcirculation of the hamster cheek pouch was visualized by the intravenous
      injection of FITC-dextran 150,000 during normal flow conditions and when flow was
      interrupted by clamping proximal to the pouch. Laser Doppler fluxmetry (LDF) was
      used to evaluate flow during control, 30 min of occlusion and after reperfusion.
      Intravital video recordings of the microcirculation during occlusion show that
      blood moves between the different arteriolar segments after occlusion and during
      the whole period of no flow. This motion was oscillatory in nature, had maximum
      velocity of order of 30 microns sec-1, and was related to progressive decrease of
      arteriolar diameter. The LDF output was in the range of 60-100 AU during control.
      This value fell in the range of 5-25 +/- 15% AU during occlusion and was assumed
      to constitute the biological zero for this system. The variability of the LDF
      signals was characterized by the autoregressive modeling power spectrum
      technique. The power spectra during control, occlusion, and reperfusion were
      similar, suggesting that motion of blood not related to perfusion or blood flow
      is present in all conditions. These findings suggest that the biological zero
      arises from signals that are not flow related and that it should be subtracted
      from the flow signal.

PMID- 8307707
TI  - Oxygen diffusion in a network model of the myocardial microcirculation.
AB  - Oxygen supply was studied in a three-dimensional capillary network model of the
      myocardial microcirculation. Capillary networks were generated using one common
      strategy to locate the capillary branchings and segments, arterioles and venules.
      Flow paths developed with different capillary flow velocities. All pressure-flow
      relationships were linear. The model includes free diffusion of oxygen within
      tissue slices that are perpendicular to the main capillary orientation. Oxygen
      pressure distributions were calculated and correlated to oxygen delivery by small
      capillary segments. It was shown that intercapillary diffusion is important for
      reducing PO2 heterogeneity. The absence of this feature leads to an oxygen
      distribution that has similar heterogeneity characteristics as the capillary flow
      heterogeneity. Such situations may also occur during simulated, elevated
      metabolic activity in a network model that allows intercapillary diffusion. On
      the basis of our simulations of metabolic vasoactivity we concluded that the
      venous PO2 is a misleading quantity to indicate tissue oxygenation. The venous
      PO2 in our model was not a good measure for the mean tissue or capillary PO2, and
      for the low oxygen pressures that exist at some locations in the network model.
      Moreover, the venous PO2 may remain constant despite considerable changes on the
      tissue PO2 distribution induced by metabolic activity.

PMID- 8307708
TI  - Microvascular responses to oxygen and muscle contraction in hypertensive Dahl
      rats.
AB  - We evaluated the possibility that increased arteriolar tone in salt-sensitive
      hypertension could be partially due to an altered vascular responsiveness to
      oxygen and/or tissue metabolites. The microvasculature of the superfused
      spinotrapezius muscle was studied with fluorescence microscopy in Dahl salt
      sensitive rats fed low (0.45%) or high (7%) salt diets for 4 weeks. High salt
      intake produced hypertension (mean arterial pressure = 162 +/- 5 mm Hg vs 130 +/-
      4 mm Hg for low salt rats, p < 0.05), and increased vascular tone at the level of
      the arcade arterioles but not in the smaller transverse or distal arterioles.
      Arcade arteriole constriction induced by increasing superfusate oxygen content
      (from 0% to 10% O2) was 60% greater in hypertensive rats than in normotensive
      rats, whereas oxygen-dependent constriction of transverse and distal arterioles
      was similar in the two groups. The oxygen-induced reduction in capillary
      perfusion (the fraction of time during which flow was observed in each vessel)
      was also greater in hypertensive than in normotensive rats. Arcade arteriole
      dilation during 2 Hz muscle contraction was significantly greater in hypertensive
      than in normotensive rats, but there were no differences between groups in the
      dilation of any other vessel type or in the capillary flow increases accompanying
      2 or 8 Hz contraction. These results suggest that a hyperresponsiveness to the
      actions of blood-borne or tissue oxygen could contribute to increased arcade
      arteriolar tone in the spinotrapezius muscle of Dahl rats with salt-induced
      hypertension. The enhanced dilation of arcade arterioles during muscle
      contraction also suggests a localized hyperresponsiveness to tissue metabolites
      in this form of hypertension.

PMID- 8307709
TI  - Hepatic microvascular regulatory mechanisms. XII. Effects of 5-HT2-receptor
      blockade on serotonin-induced intralobular hypoperfusion.
AB  - A 5-HT2-receptor antagonist (LY53857) was evaluated in the livers of male Sprague
      Dawley rats receiving a dose of serotonin (5-HT) producing systemic (arterial)
      hypotension and low flow. The specific aim of this investigation was to determine
      the cross-blocking potential of a 5-HT2 blocker having low affinity for alpha
      adrenergic and histamine H 1-receptors. This was a follow-up study to one which
      characterized the effects of normo- and hypotensive doses of 5-HT on intralobular
      perfusion and volumetric rates of blood flow at the inlet of periportal and
      outlet of centrivenous sinusoids. Twenty rats were injected intraperitoneally
      (i.p.) with 0.05 mg per g b.w. pentobarbital five min following an i.p. injection
      of 0.1 mg per 100 g b.w. LY53857. The left lobes of the livers from these rats
      were exteriorized and examined with intravital videomicroscopic and electro
      optical methods following surgical implantation of a catheter into the ileocecal
      vein. This venous catheter served as the route for endoportal infusion of
      hypotensive dose of 5-HT (10 micrograms per 100 g b.w.) in 10 rats, while the
      remaining 10 rats were given an equivalent volume of its carrier as a control
      (0.1 ml per 100 g b.w. Ringer's solution). Injection of LY53857 completely
      antagonized 5-HT-elicited low flow at the inlet of periportal and outlet of
      centrivenous sinusoids. In addition, no change in sinusoidal internal diameter
      was observed following blockade of 5-HT2 receptors. These results, in the concert
      with those from previous studies characterizing 5-HT vasoresponsiveness in the
      liver, suggest that: a) constrictor 5-HT2 receptors are localized on hepatic
      sinusoids, and b) 5-HT-provoked hypoperfusion is mediated by activation of the 5
      HT2-receptor subtype.

PMID- 8307710
TI  - AUR Memorial Award 1993. A drug system (PDH) for interventional radiology.
      Synthesis, properties, and efficacy.
AB  - RATIONALE AND OBJECTIVES: The authors synthesized and tested a novel hydrogel
      system proposed for use in extra- and intravascular radiologic interventions,
      such as chemoembolizations and embolizations, and as a vehicle for sustained drug
      release. MATERIALS: The material was specifically designed to meet the
      prerequisites of biodegradation, biocompatibility, low immunogenicity, low
      toxicity, and easy use. The material consists of a protein backbone cross-linked
      with activated bifunctional polyethyleneglycol (PEG) derivatives (PEG-derivatized
      hydrogel, [PDH]) to which are attached therapeutic (e.g., doxorubicin, a
      chemotherapeutic agent = PDH-dx) or diagnostic labels (e.g. Gd-DTPA). RESULTS:
      PDH-dx effectively reduced the risk of local tumor recurrence in a rat model when
      implanted locally after surgical tumor removal. After administration, PDH is
      degraded by proteases release from macrophages; implantations of 1 mL samples
      into paraspinal muscles of rats were completely absorbed within 4 weeks and its
      constituents were metabolized. Antibody titers (total Ig response) against the
      PDH were not detectable 1 week after implantation, whereas protein control
      substances elicited a strong response. CONCLUSIONS: PDH and its derivatives are
      relatively nontoxic, biodegradable materials for use in radiologic interventions
      and as a vehicle for sustained drug release.

PMID- 8307711
TI  - Joseph E. Whitley Award. The effect of preradiology clinical training on the
      performance of radiology residents.
AB  - RATIONALE AND OBJECTIVES: A multi-institutional study was developed to evaluate
      whether having preradiology clinical training has an effect on the quality of
      performance of radiology residents assessed both after 1 year of training and at
      the end of the 4-year residency. MATERIAL AND METHODS: Five faculty members from
      each of nine collaborating institutions that accept residents both directly from
      medical school and with postgraduate clinical training completed 1,015 evaluation
      forms on their 203 residents who had just completed their first year of radiology
      training or had finished training in the past 2 years. Each resident was
      evaluated by two senior faculty, two junior faculty, and the residency program
      director using a cross-institutionally validated, behavior-oriented, standardized
      instrument that assessed five behavioral characteristics: conscientiousness,
      curiosity, interpersonal skills, confidence, and recognition of limits. The
      differences between residents who did and did not have preradiology clinical
      training were evaluated by analysis of variance and by simple effects testing.
      RESULTS: At the conclusion of training, no significant differences in resident
      performance were found between residents who did and did not have postgraduate
      clinical training before radiology residency. Among residents who had just
      finished their first year of training, those who had had clinical training scored
      significantly higher on four of the five behavioral scales. CONCLUSIONS: Clinical
      training before radiology residency does not correlate with any measurable
      benefit in performance at the end of radiology residency. Training programs
      should consider elimination of this requirement.

PMID- 8307712
TI  - Short echo time magnetic resonance imaging of tendon.
AB  - RATIONALE AND OBJECTIVES: Current clinical magnetic resonance (MR) imaging
      studies provide almost no useful signal from normal tendon and have no clear
      advantage over other imaging modalities in the evaluation of tendon injuries. The
      authors believe that tendon MR signal may be T2-limited, and, if so, could be
      enhanced by short echo time (TE) pulse sequences. The relationship of tendon
      signal intensity and tendon infrastructure conspicuity to TE was assessed at
      three different field strengths. METHODS: Magnetic resonance imaging studies were
      performed on samples of normal equine tendon at 3 different field strengths with
      spin-echo or gradient-recalled-echo sequences of varying TE. Tendon signal-to
      noise ratios (SNR) were determined for each study and images were evaluated for
      visual evidence of tendon infrastructure. RESULTS: Tendon SNR demonstrated a
      strong inverse relationship to TE at each field strength. Signal-to-noise ratio
      values of 10 to 40 were achieved on the shortest TE studies (TE < 3 msec). Tendon
      infrastructure could be visualized and was primarily dependent on in-plane
      resolution and to a lesser extent on SNR. CONCLUSIONS: Short echo time MR imaging
      enhances tendon signal. Under optimal imaging conditions, tendon infrastructure
      can be evaluated. As high-performance gradient coil systems become available for
      clinical imaging systems, the authors believe similar results will be achievable
      on routine diagnostic studies and foresee an expanding role for MRI in the
      evaluation of tendon disease.

PMID- 8307713
TI  - Evaluation of cardiac cone-beam single photon emission computed tomography using
      observer performance experiments and receiver operating characteristic analysis.
AB  - RATIONALE AND OBJECTIVES: Single photon emission computed tomography (SPECT) with
      a cone-beam collimator improves the trade-off between detection efficiency and
      spatial resolution for cardiac imaging. However, acquisitions using orbits where
      the focus remains in a plane do not provide sufficient data for exact
      reconstruction. In the current study the authors evaluate the clinical utility of
      planar-orbit cone-beam SPECT in detecting a simple myocardial defect. METHODS:
      Observer performance experiments compared high-resolution cone-beam with same
      resolution parallel-hole and fan-beam collimator designs in myocardial defect
      detection using a computer-simulated cardiac model. The uptake of Thallium-201 in
      the myocardium and other tissue organs was modeled by a mathematical three
      dimensional upper torso phantom from which physically realistic projections were
      simulated. Eight observers viewed reconstructed transaxial images from the three
      collimator designs and indicated the certainty with which they detected a
      Gaussian-shaped defect at a specified location. RESULTS: The area under the
      receiver operating characteristic curve indicated that the cone-beam design,
      regardless of slice position, was superior to the fan-beam, which in turn was
      superior to the parallel-hole design for the specified detection task.
      CONCLUSIONS: The observer study demonstrated that reconstruction artifacts
      resulting from insufficient data sampling do not hinder obtaining improved
      diagnostic information from planar-orbit cone-beam cardiac SPECT images compared
      to conventional cardiac SPECT using parallel-hole and fan-beam collimators.

PMID- 8307714
TI  - Effects of delayed processing on mammographic phantom object detection.
AB  - OBJECTIVES: Delayed processing of films is a common occurrence in mobile
      mammography screening programs. The effects of such delayed processing on
      radiologists' detection of phantom test objects are investigated. METHODS: Twelve
      screen-film combinations were exposed using a phantom and developed after delays
      of 0, 1, 2, 3, 5, and 7 days. Films were scored by three board-certified
      radiologists specializing in mammography, based on visibility of calcifications,
      masses, fibrils, and line pairs. RESULTS: Variance analyses of mean scores
      indicate that, across screen-film combinations, there are no statistically
      significant decreases in object detection associated with delayed processing. The
      analyses do indicate, however, a statistically significant difference in scores
      unrelated to delay, attributable to the screen-film combination used.
      CONCLUSIONS: Delayed processing of mammography film does not lead to a decrease
      in the visibility of phantom test objects, despite large decreases in overall
      image optical density.

PMID- 8307715
TI  - Patterns of central acetabular osteophytosis in osteoarthritis of the hip.
AB  - RATIONALE AND OBJECTIVES: The frequency and morphology of central acetabular
      osteophyte formation were evaluated in patients with osteoarthritis. METHODS: One
      hundred preserved acetabular specimens were evaluated for the occurrence of
      central osteophytes (excrescences present in the articulation of the hip joint),
      their relationship to marginal and femoral osteophytes of the hip, and their
      radiographic appearance. RESULTS: In both specimen and patient analysis, the
      authors found that central excrescences occur commonly and appear to be related
      temporally to osteophytes of the femur and the margin of the acetabulum.
      CONCLUSIONS: The authors demonstrated a close relationship between the degree of
      marginal and femoral osteophytes with those found centrally, indicating a
      temporal relationship. The new radiographic signs discussed are: 1) a fine linear
      density associated with early osteoarthritis; 2) larger, more irregular densities
      associated with a more advanced stage of osteoarthritis; and 3) obliteration of
      the acetabular fossa by excrescences as found in severe osteoarthritis.

PMID- 8307716
TI  - Optimal sampling interval and edge detection algorithm for measurement of blood
      vessel diameter on a cineangiogram.
AB  - RATIONALE AND OBJECTIVES: The authors studied the effects of image magnification
      and the type of edge detection filter on the precision of measuring blood vessel
      diameters on coronary angiograms. METHOD: A blood vessel phantom containing five
      channels of various diameters filled with contrast medium was filmed. The
      magnifications examined were x4, x10, and x20, and the edge detection filters
      used were the first derivative, second derivative, composite, and entropy
      filters. The regression line y = a+bx was introduced, where x represents the
      nominal diameter and y the diameter measured by the edge-detection filters.
      Determination criteria were the offset, slope, and residual variance from the
      regression equation. RESULTS: The best value among three criteria was obtained
      with a magnification of x10 or x20. The entropy filter gave the best value of
      slope and residual variance. The composite filter gave the best value of offset.
      CONCLUSION: The most precise measurement is obtained when the entropy filter and
      a magnification of x10 or x20 are applied.

PMID- 8307717
TI  - Evaluation of an enhanced digital film-duplication system by receiver operating
      characteristic analysis.
AB  - RATIONALE AND OBJECTIVES: Over- or underexposure often results in poor quality
      radiographs. Using receiver operating characteristic analysis, the authors
      investigated the potential utility of a system that corrects densities in such
      images to improve the accuracy of lung nodule detection. METHODS: Chest
      radiographs were digitized by a laser film digitizer. Simulated nodules were
      superimposed on 36 improperly exposed chest radiographs. All images, with and
      without nodules, were then processed by a nonlinear density-correction technique.
      Hard-copy images were produced by a laser film printer. Eight radiologists
      evaluated the corrected and uncorrected images for the presence or absence of
      lung nodules using a continuous (0-100) confidence-rating scale. RESULT: The
      detectability of lung nodules improved significantly in the
      retrocardiac/retrodiaphragmatic regions of underexposed images and in the
      peripheral lung region of overexposed images. CONCLUSIONS: This system may
      increase diagnostic accuracy in detection of lung nodules in improperly exposed
      images.

PMID- 8307718
TI  - Methods used for liver computed tomography scanning in community radiology
      practice.
AB  - RATIONALE AND OBJECTIVES: A survey conducted in 1987 of mostly academic
      radiologists revealed that 8 of 22 (36%) respondents used bolus enhanced dynamic
      technique when performing computed tomography (CT) of the liver. In the current
      study, the authors performed a new survey of private practice radiologists that
      was over four times larger and had more comprehensive questions. METHODS: An 18
      item questionnaire was sent to 260 members of the American College of Radiology.
      The answers from 98 usable responses were tallied and analyzed. RESULTS: Forty
      six percent of the radiologists polled use bolus enhanced dynamic CT. Thirty
      three percent still use ionic contrast, and a significantly lower iodine dose was
      used when nonionic contrast was chosen. CONCLUSIONS: There is general agreement
      in the imaging literature that dynamic enhanced scanning is the method of choice
      for detecting liver masses with CT. The authors speculate that cost and
      convenience considerations strongly influence such decisions, because less than
      50% of radiologists we polled use this somewhat more expensive and time-consuming
      technique.

PMID- 8307719
TI  - Modeling of analog film-file radiographic retrievals. A Markov chain.
AB  - RATIONALE AND OBJECTIVES: Existing retrieval models for radiology film libraries
      have not incorporated the influence of previous retrievals. A Markov chain model
      for the retrieval rates from an analog film library is proposed as a means of
      considering this effect. METHODS: A Markov chain model was developed for the
      retrieval rates of an analog film library. The Markov chain model required
      identification of the states of the Markov chain, the required one-step
      transition probabilities between states, and the initial state probabilities.
      RESULTS AND CONCLUSIONS: The results from the Markov chain model compared
      favorably with the 30-day measurements (25,775 retrievals), but a large enough
      sample to determine a statistical confidence level was not considered.

PMID- 8307720
TI  - Computed tomography-pathologic assessment of laser-induced necrosis in rat liver.
AB  - RATIONALE AND OBJECTIVES: Interstitial laser photocoagulation (ILP) causes
      localized tissue necrosis. This study was performed to determine 1) whether the
      changes seen on computed tomography (CT) correspond to the necrosis
      pathologically, and 2) which CT technique best shows the necrosis. METHODS:
      Eighteen Wistar rats had ILP to their liver using a neodymium yttrium aluminum
      garnet [Nd:YAG] laser. Radio-opaque markers attached to the liver defined an
      imaging plane. Precontrast "dynamic" and delayed CT scans were performed. The
      size of necrosis was measured on CT, and macroscopically after resecting the
      liver. Computed tomography density numbers were measured from the necrotic area
      and normal liver for each CT technique. RESULTS: There was a good correlation
      between the necrosis size on CT and pathologically (P < .001). Maximum lesion-to
      liver contrast was obtained on "dynamic" CT scans. CONCLUSIONS: The extent of
      tissue density changes on CT in rat liver after ILP match the extent of necrosis
      seen pathologically. The best CT technique use assessed for evaluating laser
      induced liver necrosis is dynamic contrast-enhanced scanning.

PMID- 8307721
TI  - Gas-filled liposomes as echocardiographic contrast agents in rabbits with
      myocardial infarcts.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated gas-filled liposomes as
      echocardiographic contrast agents in rabbits with myocardial infarcts. METHODS:
      Ten rabbits underwent ligation of the left anterior descending coronary artery.
      Five animals underwent echocardiography before and after production of myocardial
      infarct (MI) and four animals had post-MI imaging only. In either case, images
      were obtained before and after injection of a single dose of 1 mL of gas-filed
      liposomes. Three radiologists blinded to clinical information reviewed the pre-
      and postcontrast images and assessed endomyocardial border definition, wall
      motion, confidence levels for normal versus abnormal wall motion and
      visualization of papillary muscle and mitral valve. RESULTS: Postcontrast scans
      showed significant improvement (P < .05) in endomyocardial border definition,
      visualization of wall motion, papillary muscle and mitral valve as well as
      increased reader confidence level. CONCLUSIONS: These results are encouraging and
      suggest that gas-filled liposomes may be a useful contrast agent for
      echocardiography.

PMID- 8307722
TI  - Effects of diatrizoate and iopamidol on spermatogenesis.
AB  - RATIONALE AND OBJECTIVES: The biological effects of iodinated contrast media were
      examined by using spermatogenesis in mouse testis as the experimental model.
      METHODS: Spermhead survival and abnormality assays were used as the biological
      end points. Diatrizoate meglumine/diatrizoate sodium and iopamidol were
      administered intravenously at equal rates and concentrations. Testicular uptake
      and clearance of these contrast agents were examined by high-performance liquid
      chromatography techniques. Appropriate mannitol solutions were employed as
      osmolality controls. RESULTS: Intravenous administration of the contrast agent or
      its respective mannitol control resulted in approximately a 30% decrease in
      spermhead count. A dose-related experiment with mannitol demonstrated that the
      spermhead count decreased rapidly until 600 mOsm/kg was reached, beyond which
      this decrease was minimal. Clearance of both contrast media was complete in
      approximately 4 hours. No significant increase in the induction of spermhead
      abnormalities was observed. CONCLUSION: Osmotic substances, such as iodinated
      contrast agents, affect the process of spermatogenesis.

PMID- 8307723
TI  - Evaluation of a new vascular occlusion device.
AB  - RATIONALE AND OBJECTIVES: A new vascular occlusion device was tested in canine
      femoral and iliac arteries and in an animal model of a patent ductus arteriosus
      (PDA). METHODS: Four variations of the vascular plug were placed into 18 iliac or
      femoral arteries of 17 mongrel dogs. Follow-up angiography was performed 1 hour
      and, if necessary, 2 hours after placement in all animals, 14 of which were then
      killed. Three dogs were followed angiographically for 2 weeks to 3 months. The
      "butterfly" plug was then tested in a canine model of a PDA. RESULTS: All plugs
      contained thrombi, and 12 of the 18 devices caused complete or nearly complete
      vascular occlusion within 2 hours. In one dog, one vascular plug had eroded
      through the vessel wall at 3 months without clinical sequelae. Successful PDA
      occlusion was achieved in 1 or 2 days in 6 of 8 dogs. Three misplacements
      occurred, one of which resulted in death. DISCUSSION: The balloon-expandable
      vascular plug appears to be a promising device for occlusion of blood vessels.
      Migration has not been observed once the device is placed, thus, sizing of the
      device appears less critical than with coils. However, modification of the
      delivery system and considerably more experience with the device are necessary to
      reduce the risk of misplacement.

PMID- 8307724
TI  - Richard Owen's vertebrate archetype.

PMID- 8307725
TI  - Ehrlich's "beautiful pictures" and the controversial beginnings of immunological
      imagery.

PMID- 8307727
TI  - Editing nature. Joseph Stalin and the "new" Soviet biology.

PMID- 8307726
TI  - Evolution, biogeography, and maps. An early history of Wallace's line.

PMID- 8307728
TI  - Current bibliography of the history of science and its cultural influences. 1993.

PMID- 8307729
TI  - Bioethics and philosophy.

PMID- 8307730
TI  - Three views of history: view the first.

PMID- 8307731
TI  - Three views of history: view the second.

PMID- 8307732
TI  - Three views of history: view the third.

PMID- 8307733
TI  - What bioethics brought to the public.

PMID- 8307734
TI  - Thirty years ago.

PMID- 8307735
TI  - But was it bioethics?

PMID- 8307736
TI  - How bioethics got its name.

PMID- 8307737
TI  - From forgoing life support to aid-in-dying.

PMID- 8307738
TI  - Why America accepted bioethics.

PMID- 8307739
TI  - The principles approach.

PMID- 8307740
TI  - Why I am neither a communitarian nor a medical ethicist.

PMID- 8307741
TI  - Smart cards, smarter policy. Medical records, privacy, and health care reform.

PMID- 8307742
TI  - The Remmelink study. Two years later.

PMID- 8307743
TI  - One more pelvic exam.

PMID- 8307744
TI  - For them rather than by them.

PMID- 8307745
TI  - The sorcerer's broom. Medicine's rampant technology.

PMID- 8307746
TI  - Less slippery.

PMID- 8307747
TI  - Less slippery.

PMID- 8307748
TI  - Whither the ELSI program?

PMID- 8307749
TI  - If only AIDS were different!

PMID- 8307750
TI  - Audit of the Scottish morbidity record 1 (SMR1) returns from an ENT unit.

PMID- 8307752
TI  - Nurses or doctors: patient choice in family planning.
AB  - For many years at one inner city practice, practice nurses trained in family
      planning and using an in-house protocol have been providing family planning
      advice and supplies to patients initially seen by the general practitioner. Two
      hundred consecutive patients attending the practice nurse or doctor for family
      planning supplies or advice were invited to complete a questionnaire to assess
      their preferred career and their overall satisfaction with the services. The
      patients' perceptions of whom they thought most appropriate to deal with their
      family planning requirements were explored. The patients who had seen the nurse
      rather than the doctor claimed to be more up to date with their cervical smear,
      to have had their blood pressure (BP) checked, and to be generally more satisfied
      with the consultation. Apart from the initial consultation for oral contraception
      most patients stated they would prefer to attend the nurse.

PMID- 8307751
TI  - The epidemiology of Haemophilus influenzae invasive disease in Scotland prior to
      immunisation.
AB  - Immunisation against Haemophilus influenzae b (Hib) was added to the UK childhood
      vaccination schedule on 1 October 1992. Based on reports of laboratory isolations
      from blood and/or CSF, the epidemiology of Haemophilus influenzae invasive
      disease in Scotland during the last full year before immunisation (1991) is
      reviewed. In children aged under five years the estimated incidence of infection
      (25.5 per 100,000) is higher than that previously reported from Scotland, but
      lower than estimates from Glasgow and other UK studies. However, the age-sex and
      seasonal distribution is consistent with previous surveys. As in England and
      Wales, there appears to be regional variation in incidence within Scotland,
      although this may simply reflect differences in the completeness of laboratory
      reporting. In addition to 113 laboratory reports of H. influenzae invasive
      infection, a retrospective search of hospital discharge data and death
      registrations identified a further 51 and two cases respectively, some of whom
      may be genuine. In spite of reservations about hospital discharge data, this
      raises the possibility that there may be an element of under-reporting by
      laboratories. With the advent of record linkage of hospital discharge data, it
      would be prudent to monitor the impact of the Hib vaccine programme using this
      data source in addition to laboratory reports and death registrations.

PMID- 8307753
TI  - An evaluation of the personal child health record in Fife.
AB  - Personal child health records were introduced in Fife in March 1992; an
      evaluation carried out in November 1992-February 1993 sought the views of both
      parents and health professionals and examined a sample of the records. All 104
      parents who were interviewed considered it important that they hold a copy of
      their child's health record. The majority made good use of the personal child
      health record by bringing it regularly to clinics and by reading or completing
      the appropriate sections. The views of health professionals were mixed and some
      specific problems were raised. However, there is still relatively limited
      experience with the record in Fife; it is possible that professional endorsement
      of it will grow with increasing experience in its use. Suggestions for
      improvements should be acted upon where possible to encourage regular and correct
      use. The loose leaf format of the record facilitates the incorporation of
      amendments. The use of the record in Fife should be promoted by emphasising that,
      despite individual views of health professionals about the record, the great
      majority of parents value it and the improved access to the information about
      their child's health which it represents.

PMID- 8307754
TI  - Differences in expectation of life between Glasgow and Edinburgh. Implications
      for health policy in Scotland.
AB  - Inequality in health is not a minor issue confined to small areas, but a major
      feature of contemporary Scotland and a massive public health problem. Comparison
      of mortality rates in Glasgow and Edinburgh is instructive, not only because of
      the large current difference in mortality rates between the cities, but also
      because the availability of data for both cities for most of this century
      provides an opportunity to view current differences from a historical
      perspective. This shows that current large differences in disease-specific
      mortality rates are part of a broader pattern of earlier death from all causes
      which has been established at least by the age of 25 in successive generations.
      Whether and how this pattern may be reversed and prevented deserves urgent
      discussion and debate. In the meantime, differences in life expectancy between
      sections of the Scottish population should be included as part of routine health
      monitoring. Reduction in differences in life expectancy should also become a
      national health target.

PMID- 8307755
TI  - Drug injectors in Glasgow: a community at risk? A report from a multidisciplinary
      group. The Possilpark Group.
AB  - In 1987 it became apparent that the number of drug injectors with HIV infection
      living in a district in the north of Glasgow was increasing. As this area was
      well served by a wide variety of clinical, epidemiological and laboratory
      facilities, a multidisciplinary group was convened to examine the extent and
      spread of infection, and its relationship to behavioural and environmental
      factors. By 1989 a World Health Organisation working group had developed a
      standardised methodology, consisting of an interview schedule and voluntary
      anonymous HIV testing procedures. The study has been implemented annually in
      Glasgow since 1990, with a collateral project evaluating prevalence of injecting
      drug use in the general population. The Glasgow HIV Behavioural and Prevalence
      Study was designed to yield as representative as possible a sample of the city's
      injectors, respondents being drawn from a variety of in-treatment and out-of
      treatment sites. Of the estimated 8,500 injectors in Glasgow (1.35% of the
      population aged 15-55), 503 and 535 injectors were recruited to the study in 1990
      and 1991 respectively. Over 90% of respondents injected daily and reported
      injecting, on average, four different types of drugs in the six months prior to
      interview, the three most commonly injected drugs being buprenorphine, heroin and
      temazepam. There is evidence of HIV risk reduction for sharing of injecting
      equipment and for using condoms with casual sexual partners. Salivary testing has
      proved to be successful, less than 5% of respondents refusing to be tested; the
      prevalence rate was 1.8% in 1990 and 1.1% in 1991. While HIV prevalence remains
      low, all-cause mortality among injectors in Glasgow is high; drug injecting is
      probably responsible for more deaths among people aged under 40 than any other
      factor. At the present time, the drug injecting epidemic in Glasgow poses a
      considerable challenge to the city's public health services.

PMID- 8307756
TI  - Medical staffing in the National Health Service in Scotland in 1992.

PMID- 8307757
TI  - AIDS and the African American woman: the triple burden of race, class, and
      gender.
AB  - The disproportionate impact of human immunodeficiency syndrome (HIV) disease on
      African American women is devastating to their lives, their families, their
      communities, and our society. Among AIDS cases in women, 52.5% are black. African
      American women with HIV disease constitute one of the least powerful and most
      burdened segments of society. The African American woman whose behavior places
      her at risk for HIV infection must be the focus of increased prevention and
      treatment efforts. This article will describe risk factors for HIV infection and
      AIDS educational needs of women at risk. The interaction of race, gender, and
      social class will be explored. The controversy over medical manifestations of HIV
      will be addressed within the context of the social reality of African American
      women at risk. Reproductive rights and public policy issues will be discussed.
      Health educators must overcome their fear, class prejudice, and racial bias in
      order to form the interracial coalition necessary to lead our nation in the
      struggle to stop the devastation of AIDS among African American women and
      children.

PMID- 8307758
TI  - A meta-evaluation of nutrition education intervention research among pregnant
      women.
AB  - Inadequate nutrition during pregnancy retards human fetal growth and increases
      the risk of delivering a low birthweight (LBW) infant. Some studies place
      particular emphasis on reducing LBW through improved nutrition. Consensus
      documents have strongly recommended intense nutrition education programs for
      patients at risk. Despite this well-defined need few methodologically rigorous
      studies have been conducted to evaluate the behavioral impact of nutrition
      education for pregnant patients. Criteria are recommended in the following areas:
      (1) research design, (2) sample size and power, (3) specification of population
      characteristics, (4) measurement quality, and (5) replication. The methodological
      quality of completed evaluations are reviewed using these criteria. The authors
      advocate guidelines for future investigators for conducting rigorous trials in
      this critical public health area.

PMID- 8307759
TI  - Persuasive conversations between friends about health and safety precautions.
AB  - One hundred eighty-five conversations in which a college student attempted to
      convince a friend to adopt a health or safety precaution were examined. A
      detailed category coding system was developed to describe the content of such
      conversations and to answer nine specific questions about these interactions.
      Among other results, the data showed that subjects spend very little time
      describing the nature of the harm that might occur and usually speak of
      protection in dichotomous, all-or-none terms rather than acknowledging degrees of
      risk. Much time is spent discussing the correct actions to take and the problems
      faced in carrying out these actions. Initial and 2-month assessments of of
      persuasiveness found no significant relationships between the presence of
      specific themes and changes in intentions or behavior. The observed content of
      these conversations is discussed in relation to current theories of self
      protective behavior and likely mechanisms of social influence.

PMID- 8307760
TI  - Using focus groups to develop health surveys: an example from research on social
      relationships and AIDS-preventive behavior.
AB  - Focus group data can inform the choice of words or phrases in a questionnaire,
      the construction of items to measure a given concept, the formation of new
      hypotheses, and the development of survey procedures. To date, few examples exist
      to show researchers in health behavior and health education how they might use
      focus groups for these purposes. This paper provides an example of group
      discussions that were held with gay and bisexual men on the topic of their
      experiences of the human immunodeficiency virus/acquired immune deficiency
      syndrome (HIV/AIDS) epidemic and illustrates the many ways that focus groups
      assist in questionnaire development.

PMID- 8307761
TI  - Assessment of adolescent refusal skills in an alcohol misuse prevention study.
AB  - Although many substance abuse prevention programs seek to enhance the ability of
      adolescents to refuse offers of alcohol and other drugs, few report assessments
      of refusal skill ability or its relationship to substance use. This report
      describes a procedure to assess the ability of adolescents to refuse the offer of
      a beer, and presents the findings of those assessments as well as their
      relationships to alcohol misuse prevention knowledge, susceptibility to peer
      pressure, internal health locus of control, self-esteem, and alcohol use and
      misuse. A one-third random sample (n = 1012) of 10th graders participating in a
      longitudinal evaluation of an alcohol misuse prevention curriculum was assessed
      individually. Students rated their own refusals, which were also rated by trained
      female and male raters. The results indicated that adolescents refuse the offer
      of a beer only somewhat convincingly. Those adolescents with better refusal
      skills had higher levels of alcohol misuse prevention knowledge, especially
      regarding resisting pressures to use alcohol and the application of knowledge of
      typical alcohol-related situations. They also reported less susceptibility to
      peer pressure, greater internal health locus of control and self-esteem, and less
      alcohol use and misuse. The results provide support for teaching refusal skills
      in substance abuse prevention programs and for assessing refusal skills in the
      evaluation of such programs.

PMID- 8307762
TI  - Participation in worksite health promotion: a critique of the literature and
      recommendations for future practice.
AB  - One of the major rationales for conducting health promotion/disease prevention
      activities at the worksite is the potential to reach a high percentage of
      employees, including many who would otherwise be unlikely to engage in preventive
      health behaviors. Most studies of worksite health promotion do not report
      participation data, but among those that do, definitions of participation and
      participation rates vary dramatically. In general, men and blue-collar employees
      appear less likely to participate, but little is known about other employee
      variables related to participation. There have been few studies of worksite
      characteristics associated with participation and even fewer experimental
      evaluations of interventions to increase participation. In this paper we review
      what is known about participation in worksite health promotion programs and
      recommend procedures for defining participation for different types of programs,
      for reporting determinants of participation, and for increasing participation. We
      conclude that participation is both an important process measure and an outcome
      that should be reported routinely. Participation data have important implications
      for generalizability of results, feasibility of interventions, and health
      outcomes.

PMID- 8307763
TI  - Factors associated with AIDS-related behavioral intentions among high school
      students in an AIDS epicenter.
AB  - Using data from a cross-sectional survey of 531 predominantly black and Hispanic
      10th graders in two New York City schools, the explanatory power of predictors of
      intentions to engage in sexual intercourse, to have multiple intercourse
      partners, and to use condoms was compared. Theoretically derived predictor
      variables (i.e., susceptibility, severity, benefits, barriers, self-efficacy,
      values, norms) were derived from the health belief model, social cognitive
      theory, and a model of social influence. One half of sampled students definitely
      intended to have sexual intercourse in the next year, one tenth definitely
      intended to have multiple partners, and two thirds definitely intended to use
      condoms. In multivariate analyses, variables derived from the model of social
      influence and from social cognitive theory were most strongly associated with the
      three investigated behavioral intentions; however, certain background and health
      belief variables also contributed to the explained variance in intercourse and
      multiple partner intentions.

PMID- 8307764
TI  - Use of focus group methodology to develop an asthma self-management program
      useful for community-based medical practices.
AB  - Health education programs developed in academic medical centers are not optimally
      disseminated to community clinical settings. Strategies are needed to translate
      the findings of research on health education programs into programs useful in a
      wide range of health care settings. Focus group techniques were used to provide
      data for revising a successful university-based asthma self-management program to
      make it more practical for use by community physicians. Physicians representing a
      variety of specialties attended the sessions and provided feedback on the utility
      of various components of the original program. The discussions revealed that many
      physicians felt they did not have the time or resources to conduct the original
      program and identified elements viewed as impractical. This physician input
      contributed significantly to the development of a revised program with a briefer,
      less costly intervention. The revised program was later evaluated by focus group
      participants. Eighty-eight percent of those who evaluated the revised program
      agreed they would be able and willing to use the program in their own practices.
      As a formative evaluation tool, the focus group technique made available useful
      information that would have been difficult to obtain through evaluation forms
      alone.

PMID- 8307765
TI  - Population prevalence and correlates of stages of change in physical activity.
AB  - Stages of change for exercise, sociodemographic variables, and beliefs about the
      health benefits of exercise were obtained for a representative sample of
      Australian adults (N = 4404). Logistic regression analysis was used to examine
      the relationship between exercise stage of change and sociodemographic variables
      and beliefs about the benefits of exercise. Thirteen percent of respondents
      stated that they did not exercise and did not intend to start; 10% stated that
      they did not exercise but were thinking of starting; 16% stated that they
      exercise occasionally and were not thinking of doing more; 23% stated that they
      exercised occasionally and were thinking of doing more; and 38% stated that they
      exercised regularly and intended to continue. Intention to do more exercise
      generally decreased with increasing age, but increased with level of education.
      An increased frequency of exercise and an intention to do more exercise was
      associated with the belief that exercise would help to prevent heart disease and
      with a higher level of education. The results provide a useful profile of the
      exercise habits (and intention to change those habits) of population subgroups.
      Public communication campaigns on the benefits of physical activity should focus
      particularly on those who do not intend to exercise, older adults, and the less
      well educated.

PMID- 8307766
TI  - Assessing the stages of change and decision-making for contraceptive use for the
      prevention of pregnancy, sexually transmitted diseases, and acquired
      immunodeficiency syndrome.
AB  - A synergistic approach was taken to examine contraceptive use adoption for two
      related behaviors: pregnancy prevention and the prevention of sexually
      transmitted diseases (STDs), including human immunodeficiency virus
      (HIV)/acquired immunodeficiency syndrome (AIDS). One hundred twenty-three young
      adults responded to questionnaire items based on two constructs from the Trans
      theoretical Model of Change, the Stages of Change and Decisional Balance, as well
      as other pertinent variables. In Phase 1, two Decisional Balance measures were
      developed: One for the prevention of pregnancy and one for disease prevention.
      Final versions of both measures consisted of two 10-item scales: one representing
      the positive aspects (PROS) and one representing the negative aspects (CONS) of
      contraceptive and condom use. In Phase 2, the same individuals were staged for
      both pregnancy and disease prevention according to their readiness to change for
      contraceptive and condom use. MANOVAs and ANOVAs indicated that the PROS and CONS
      for both measures were related to stage of change for both contraceptive and
      condom use. Results from this pilot study were consistent with prior applications
      of the Trans-theoretical Model to the cessation of such problem behaviors as
      smoking and to the adoption of positive health behaviors such as exercise
      acquisition.

PMID- 8307767
TI  - Predictors of home radon testing and implications for testing promotion programs.
AB  - Four data sets (total N = 3,329) are examined to identify the predictors of home
      radon testing. The data, interpreted in terms of a stage model of radon testing
      behavior, reveal that the variables predicting transitions between stages change
      as people move from one stage to the next. Thinking about radon testing (vs.
      never having even considered testing) is best predicted by general radon
      knowledge and by knowing other people who are concerned or have tested. Once
      contemplating testing, the decision to test is most closely related to the
      perceived likelihood of a home radon problem. Finally, there are few differences
      between people who say they have decided to test and those who have already
      tested. Instead situational factors--including difficulties in locating and
      choosing among test kits--appear to constitute the final barrier to testing. The
      ways in which these findings might assist the design of radon outreach programs
      are discussed, and specific outreach recommendations are advanced.

PMID- 8307768
TI  - Effect of perceived barriers on compliance with antihypertensive medication.
AB  - Noncompliance with antihypertensive medication remains an obstacle to the
      management of hypertension, and despite research efforts over the past decade,
      the predictors of noncompliance remain unclear. According to values expectancy
      theory, individuals rationally choose noncompliance when the barriers or costs of
      treatment outweigh the expected benefits. Noncompliance, therefore, is likely to
      occur when net costs of treatment are high. Using a cross-sectional study design
      among subjects (n = 197) attending a specialized clinic for hypertension, we
      measured "net barriers" (costs), self-reported compliance, and possible
      determinants of noncompliance, including socio-demographics, the medical regimen,
      and locus of control. The effect of each quartile of the net barriers score
      (none, low, moderate, and high) on compliance, controlling for potential effect
      modifiers, was assessed using logistic regression modeling. Noncompliance (47%)
      was associated with younger age, higher salt use, longer duration of treatment,
      and higher levels of net barriers, but duration of treatment modified the effect
      of net barriers. Among subjects in short-term treatment, noncompliance increased
      with severity of net barriers suggesting a dose-response effect. In contrast,
      patients in long-term treatment showed no dose-response effect but a consistent
      association between noncompliance and levels of net barriers. Subjects at greater
      risk for noncompliance, however, were those who reported high net barriers,
      regardless of duration of treatment. Net barriers accounted for 50% of the
      noncompliance and appeared most important for patients who were younger or in the
      early stages of treatment. Implications for health care providers are discussed.

PMID- 8307769
TI  - Lay evaluation of symptoms by older people: an assessment of potential risk.
AB  - This paper examines the appropriateness of lay evaluations of potential risk of
      symptoms among a sample of 667 elderly people living in community settings. Data
      were gathered through personal interviews and 3 weeks of structured health
      diaries in which older respondents recorded the symptoms they experienced.
      Potential medical risk was determined on a symptom by symptom basis based on
      clinical information gathered during the interviews. Almost three fourths of the
      respondents exhibited potential clinical risk for at least one symptom they
      experienced during the 3-week diary period. One in eight respondents was judged
      at risk yet gave no evidence of physician consultation, either during or prior to
      the diary period. Implications of these results for health education designed to
      improve consultation decisions among elderly people are discussed.

PMID- 8307770
TI  - Findings from the Horizontes Acquired Immune Deficiency Syndrome Education
      project: the impact of indigenous outreach workers as change agents for injection
      drug users.
AB  - A human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
      intervention using indigenous outreach workers was implemented with Hispanic
      injection drug users (IDUs) and their sexual partners in three locations: Laredo,
      Texas; San Diego, California; and San Juan, Puerto Rico. A total of 2,169
      subjects were contacted, given health education, HIV antibody testing, and follow
      up counseling. This article reports on the 1,616 IDUs (75%) who completed the
      initial and follow-up interviews. The results indicated significant increases in
      health knowledge on AIDS, decreases in needle risk drug taking behaviors, some
      decreases in sex risk behaviors, and more realistic perceptions of personal AIDS
      risk. Using multivariate analyses, gender (male) and increasing age (older than
      age 25 years) were the strongest predictors of behavior change. Surprisingly, the
      identification of a positive HIV serostatus was not a significant predictor of
      behavior change. Although intended as a comparison study between contrasting
      levels of intervention, logistical and administrative problems undermined the use
      of a true quasi-experimental design. Nonetheless, the results from this research
      suggest that the use of indigenous outreach workers is an effective means of
      combatting the spread of HIV in this difficult to reach population. Some
      programmatic recommendations are provided for future efforts of this kind,
      particularly in relation to role conflicts experienced by outreach workers.

PMID- 8307771
TI  - Breast cancer screening among older Hispanic women: knowledge, attitudes, and
      practices.
AB  - A survey was conducted with 409 Hispanic and 138 Anglo women in Tucson, Arizona,
      to assess their knowledge of breast cancer and cancer screening tests, their
      attitudes toward breast cancer and cancer screening, and their use of screening
      tests. There were few differences between these two groups in use of breast
      cancer screening tests, with both group falling well below the recommended levels
      of screening frequency. Clinical breast exam was most often used, followed by
      breast self-exam, with mammography a distant third. Levels of knowledge about the
      risks for breast cancer and the ways to detect it were also low. Comparison with
      national data show Arizona women to have lower rates of breast cancer screening
      than the national average; this may be due to the absence of the Medicaid program
      in Arizona. The rates for Tucson Hispanics, although lower than that for Anglos,
      are comparable with the findings of other studies. More needs to be done to alert
      all older women about breast cancer screening, but more specific attention needs
      to be paid to the population of older Hispanic women. We suggest some culturally
      relevant strategies to address this problem.

PMID- 8307772
TI  - Efficacy of a home-based human immunodeficiency virus prevention video program
      for teens and parents.
AB  - Family-based communication about sexual behavior and sexuality is a predominate
      theme in the key risk reduction and service objectives for human immunodeficiency
      virus (HIV) prevention and related issues in Healthy People 2000. These
      recommendations are particularly poignant for younger adolescents who are not yet
      sexually active and whose social orientation is primarily to family and parents.
      A family-centered, home-based, video program to foster parent and teen knowledge
      and communication regarding issues related to HIV prevention and to increase
      family and teen communication skills was used in an intensive field test of
      program efficacy. Sixty-nine families with at least one adolescent age 12 to 14
      years were recruited through their primary-care physicians and were randomly
      assigned to either experimental (video with information and skills training) or
      control (video with information only) conditions in a pre-posttest with a 4-month
      follow-up design. Both versions of the video program resulted in substantial
      increases in HIV-related knowledge for parents and teens, but only the skill
      training (experimental) version produced increases in knowledge of communication
      skills and behavioral demonstrations of family problem solving. Approaches for a
      broader and more effective parent-training video program and for dissemination
      through primary-care physicians are discussed.

PMID- 8307773
TI  - Development of the Adolescent Health Concerns Inventory.
AB  - Health concerns of adolescents are important factors to consider when developing
      and implementing school health education programs. In addition, an understanding
      of adolescent concerns compared to their teachers' and parents' beliefs about
      adolescents' concerns may enhance communication between adolescents and adults.
      Despite the need to identify the health concerns of adolescents and beliefs about
      them among parents and teachers, few instruments exist. The inventory described
      in this article is one approach to assessing adolescent health concerns. Three
      forms of the Adolescent Health Concerns Inventory (AHCI) were developed to
      assess: (1) the health concerns of adolescents, (2) teachers' beliefs about
      adolescent health concerns, and (3) parents' beliefs about adolescent health
      concerns. The final version of the instrument contained 150 health-related items
      grouped into 12 topical subscales. Reliability estimates for the 12 subscales as
      measured by Cronbach's alpha ranged from .76 to .92. A panel of experts was used
      to assess content validity. Construct validity was assessed using principal
      components factor analysis. All items were positively loaded on factor 1.
      Readability was estimated at the eighth grade as measured by the SMOG readability
      formula. Psychometric characteristics of the instrument and recommendations for
      the use of the ACHI are presented.

PMID- 8307774
TI  - Heterogeneous expression of ornithine decarboxylase gene in the proximal tubule
      of the mouse kidney following testosterone treatment.
AB  - The expression of the ornithine decarboxylase (ODC) gene in the mouse kidney
      following testosterone treatment was examined using in situ hybridization
      histochemistry. Testosterone (n = 5) or vehicle (n = 5) was subcutaneously
      injected (1 mg/animal) into male BALB/c mice (8 weeks in age) 14 h before
      sacrifice. Animals were sacrificed under ether anesthesia, their kidneys were
      removed and immediately frozen in liquid nitrogen. Frozen sections (10-microns
      thick) were cut on a cryostat. Sections were hybridized with 35S-labeled sense or
      antisense RNA probe. The hybridization continued for 24 h at 50 degrees C and
      emulsion autoradiography was subsequently performed. A marked increase in ODC
      mRNA was exclusively detected in the proximal tubule of the renal cortex in the
      testosterone-treated animals. The hybridization signal was greater in the outer
      portion of the proximal tubule than in the inner portion. No significant
      hybridization signal was detected either in the distal tubule, renal corpuscle or
      peritubular tissues. These results indicate that testosterone induces the
      expression of the ODC gene in the proximal tubule of the renal cortex, leading to
      the increase in ODC activity in the same region.

PMID- 8307775
TI  - Cell differentiation of alveolar epithelium in the developing rat lung:
      ultrahistochemical studies of glycoconjugates on the epithelial cell surface.
AB  - Glycoconjugates on the surface of pulmonary epithelial cells were
      ultrahistochemically examined in the fetal, neonatal and adult rat lung. Lectin
      and colloidal iron staining procedures were performed in combination with
      digestion using carbohydrate-degrading enzymes or methylation. The glycoconjugate
      composition of columnar cells at 16 days gestation was similar to that of
      cuboidal cells at 19 days gestation. Glycoconjugate differentiation on the cell
      surface occurred at 20 days gestation, and especially the loss of soybean
      agglutinin (SBA) binding sites could be detected on type II cells. The contents
      of Ricinus communis agglutinin-I (RCA-I) and Concanavalin A (Con A) binding sites
      on type II cells also began to decrease. On the contrary, the content of sulfated
      saccharides decreased on the surface of type I cells during development.
      Glycoconjugate differentiation on both type I and II cells was completed with the
      disappearance of hyaluronic acid and peanut agglutinin (PNA) binding sites; type
      I and II cells acquired a similar histochemical composition to that on adult type
      I and II cells at 5 days after birth. Both type I and II cells share a common
      early precursor cell, that is, the cuboidal epithelial cell at the canalicular
      stage.

PMID- 8307776
TI  - Immunohistochemical localization of extracellular matrix in perivillous fibrinoid
      of normal human term placenta.
AB  - The extracellular matrix of perivillous fibrinoid in normal human term placenta
      was investigated by means of the indirect immunofluorescent technique. Polyclonal
      antibodies to collagen types I, III, IV, V, fibronectin, fibrinogen, laminin,
      entactin and heparan sulphate proteoglycan and monoclonal antibodies BC-1, IST-9
      and IST-4 to human fibronectin were used. The antigens can be grouped according
      to their presence in fibrinoid as abundant (fibrinogen, fibronectin, heparan
      sulphate proteoglycan, basement membrane collagen types IV and V), absent
      (laminin) and variable between fibrinoids (interstitial collagen types I and III,
      entactin). Our results also demonstrate that fibronectin in fibrinoid originates
      from placental cells (presumably cytotrophoblast). Monoclonal antibodies BC-1 and
      IST-9 specific to tissue fibronectin do not stain neighbouring placental
      extracellular matrix but do bind to fibrinoids on the same sections. Work by
      other authors has presented evidence that fibrin actually originates from
      maternal blood and even makes an attempt to substitute the term "fibrinoid" for
      "fibrin deposition". Our data on the composition of perivillous fibrinoids and
      the abundance of extracellular matrix components do not support this view and
      suggest that fibrinoid is a more relevant term for this interesting phenomenon,
      which deserves further investigation.

PMID- 8307777
TI  - Multicolour preparations for in situ hybridization using precipitating enzyme
      cytochemistry in combination with reflection contrast microscopy.
AB  - We have further developed a method for the detection of different enzyme
      cytochemical reaction products by means of reflection contrast microscopy (RCM).
      By embedding these enzyme precipitates in a protein matrix, we were able to
      prevent the reaction products from dissolving in immersion oil, which is required
      for RCM analysis. The applicability of the RCM procedure is, therefore, extended
      to a range of cytochemical enzyme precipitation methods, which normally result in
      oil soluble reaction products. To test their usefulness, these enzyme
      precipitates have been used in single- and well as double-label in situ
      hybridization (ISH) procedures to visualize a number of DNA target sequences by
      several different reflection colours, i.e. white, yellow and red. Three
      repetitive DNA probes for the (sub)centromeric regions of chromosomes 1, 7 and
      17, as well as a repetitive DNA probe for the telomeric region of chromosome 1,
      and two cosmid DNA probes (40 kb each) for both arms of chromosome 11 could be
      detected with high efficiency in both interphase and metaphase preparations.
      Moreover the enzyme precipitates were shown to be stable upon exposure to
      excitation light or upon storage. It may be concluded that these findings render
      RCM a sensitive method for the visualization of multiple targets in biological
      specimens.

PMID- 8307778
TI  - Immuno- and lectin histochemistry of epithelial subtypes and their changes in a
      radiation-induced lung fibrosis model of the mini pig.
AB  - Cell types of lung epithelia of mini pigs have been studied using a panel of
      monoclonal and polyclonal antibodies against cytokeratins (CKs) and vimentin and
      three lectins before and after radiation-induced fibrosis. In normal tissues,
      CK18 specific antibodies reacted above all with type II alveolar epithelial
      cells, while CK7 and pan CK-specific antibodies stained the whole alveolar
      epithelium. In bronchial epithelial cells, CKs 7, 8, 18 and focally CKs 4 and 13
      as well as vimentin were found. Cell specificity of the CK pattern was confirmed
      by double label immunofluorescence using type II cell-specific Maclura pomifera
      (MPA) lectin, type I cell specific Lycopersicon esculentum (LEA) lectin and
      capillary endothelium-binding Dolichos biflorus (DBA) lectin. In experimental
      pulmonary fibrosis, enhanced coexpression of CK and vimentin was observed in
      bronchial epithelium. Subtypes of alveolar epithelial cells were no longer easily
      distinguishable. CK18 was found to be expressed in the entire alveolar
      epithelium. The gradual loss of the normal alveolar epithelial marker, as seen by
      the binding of MPA to type I-like cells, of LEA to type II-like cells and the
      partial loss of MPA-binding to type II cells, was paralleled by the appearance of
      CK4, typical for squamous epithelia, and the occurrence of DBA-binding in
      epithelial cells. Implications of these results for general concepts of
      intermediate filament protein expression and lectin binding in the fibrotic
      process are discussed.

PMID- 8307779
TI  - Immunohistochemical localization of glucose transporters and insulin receptors in
      human fetal membranes at term.
AB  - The localization has been investigated of the isoforms GLUT1, GLUT3 and GLUT4 of
      glucose transporter proteins as well as of insulin receptors. Fetal membranes (n
      = 10) were examined by immunohistochemical methods at the light and electron
      microscopic levels using mono- and polyclonal antibodies. In all amnion
      epithelial cells, GLUT1 and GLUT3 antibodies were bound to the apical membrane.
      Very rarely the GLUT1 antibody also immunostained the basolateral membrane and
      reacted weakly with the endomembrane system and membranes of the lateral cell
      protrusions. Fibroblasts reacted with the antibodies against GLUT1, GLUT4 and
      insulin receptor, whereas they were labelled only in one case with GLUT3
      antibody. Cytotrophoblast cells were only stained with antibodies against GLUT1
      and GLUT3. Antibodies against GLUT4 only reacted with fibroblasts in the
      membranes. On amnion epithelial cells, weak immunoreactivity with insulin
      receptor antibodies was detected only at the electron microscopic level. The data
      indicate: (1) GLUT1 is located on all cells of the amnion, whereas GLUT3 is
      present in detectable amounts only on amnion epithelial cells and
      cytotrophoblast; (2) GLUT1 and GLUT3 on amnion epithelial cells are predominantly
      located on the apical surface; (3) GLUT4 and insulin receptors are not regularly
      expressed. We suggest that amnion epithelial cells cover their basal glucose
      requirements from the amniotic fluid and not from the maternal circulation.

PMID- 8307780
TI  - Comparison of 3' and 5' biotin labelled oligonucleotides for in situ
      hybridisation.
AB  - Oligonucleotide probes enzymatically labelled at the 3'-end with biotin have been
      used successfully to detect target RNA and DNA in combination with in situ
      hybridisation. Addition of multiple biotin residues to the 3'-end increases the
      hybridisation signals, but it is not known whether the same principle is
      applicable to the 5'-end. We have labelled a 35-base oligonucleotide during
      synthesis with 1, 5 and 12 biotin molecules at the 5'-end and compared it to
      conventional 3'-labelling. In additional experiments the probes were labelled at
      both ends. Probes were applied to histological sections obtained from paraffin
      embedded cell-clot-complexes that contain uninfected and Rhinoviral-infected
      cells, using a standard in situ hybridisation protocol with appropriate controls.
      Hybridisation signals were compared for intensity of cytoplasmic signal and
      sensitivity as number of positive cells. Both parameters increased in parallel
      with higher numbers of biotin residues attached to the 5'-end and 12 biotin
      residues were almost as effective as 3'-enzymatic tailing. The sensitivity could
      be increased above that of either 3'- or 5'-labelling by the addition of residues
      at both ends of the probe. The 5'-attachment of biotin residues can extend the
      value of oligonucleotide probes employed for in situ hybridisation and yield
      increased sensitivity when combined with 3'-enzymatic labelling.

PMID- 8307781
TI  - Do neuroendocrine cells in human prostate cancer express androgen receptor?
AB  - The presence of androgen receptors (AR) in neuroendocrine cells was investigated
      in benign tissue of 10 prostatectomy specimens, in 12 prostatic adenocarcinomas
      with focal neuroendocrine differentiation and in 1 case of a pure neuroendocrine
      small cell carcinoma of the prostate. Neuroendocrine cells were defined by their
      reactivity with an antibody to chromogranin A. Monoclonal antibody F39.4 directed
      against the amino-terminal domain of the AR molecule was used to detect AR. AR
      and chromogranin A were simultaneously visualized with a double
      immunofluorescence technique. The results indicate that chromogranin positive
      cells in both benign and malignant prostatic tissue lack detectable expression of
      AR. No effect of endocrine therapy was noted. These results are in agreement with
      the hypothesis that prostatic neuroendocrine tumour cells represent an androgen
      insensitive cell population, which incidentally may expand to replace the
      androgen-sensitive tumour cell population during androgen ablation therapy.

PMID- 8307782
TI  - 4th Asia-Oceania Histocompatibility Workshop. April 22-29, 1993. Perth, Western
      Australia. Proceedings.

PMID- 8307783
TI  - New major histocompatibility complex genes.
AB  - The MHC is a region of some 4 megabases that has been studied intensively owing
      to the large number of diseases that are associated with susceptibility genes
      within this region of the genome. The total number of genes located within the
      MHC is now approximately 100, but more can be predicted. Recently identified
      genes within the MHC include PERB6, a large gene producing multiple transcripts
      located between HLA-B and TNF, and PERB1, a member of the protein tyrosine kinase
      gene family. PERB6 was identified by YAC probing of tissue blots, while PERB1 was
      identified by genomic sequencing.

PMID- 8307784
TI  - Characterization of 4AOHW cell line panel including new data for the 10IHW panel.
AB  - There will be a continuing need for well characterized panels of EBV-transformed
      lymphoblastoid cell lines. Selection of the 4AOH panel was based on prior MHC
      typing and was intended to ensure representation of ancestral haplotypes from
      various racial groups. Cells from nonhuman primates, bone marrow donor-recipient
      pairs, and patients with IDDM were included. Selected cells from the 10IHW were
      included to enable further characterization. Cells were distributed to
      participants in the 4AOHW and were typed at multiple loci by a variety of
      procedures. Non-HLA genes such as TNF were included. Since the cells were
      distributed "blind" with hidden replicates, it was possible to evaluate the
      quality of the typing data. An approach to data management is described. The best
      current estimates of the typing of these cells are presented. The panel will be
      useful since it provides standards for most alleles at most loci. Since the cells
      are so well characterized, they represent a useful resource for MHC sequencing
      and for the evaluation of new typing procedures.

PMID- 8307785
TI  - Differences in the central major histocompatibility complex between humans and
      chimpanzees. Implications for development of autoimmunity and acquired immune
      deficiency syndrome.
AB  - Chimpanzees (Pan Troglodytes) and humans are closely related and belong to the
      same subfamily, Homininae. The approximately 1.8% genetic difference that exists
      between humans and the chimpanzees must be responsible for observed differences
      between these two species. It has been shown that chimpanzees can be infected
      with HIV, but AIDS has not been reported. Furthermore, the prevalence of
      autoimmune diseases may be low in this species. For instance, type II diabetes
      occurs, but type I (autoimmune) diabetes (IDDM), to our knowledge, has not been
      reported. In humans, susceptibility genes for MG and IDDM have been localized to
      the region between TNF and HLA-B. This region may also influence the rate of
      progression to death after HIV infection. We have identified differences in this
      region between humans and the chimpanzees. As shown by PFGE, the TNF to Patr-B
      region in the chimpanzees is approximately 130-160 kb shorter than the equivalent
      in humans. Southern and sequence analyses indicate that the deletions in
      chimpanzees (insertions in humans) include one copy of CL (approximately 10 kb)
      and the X sequences (< 30 kb). Obviously, other deletions/insertions
      (approximately 120 kb) need to be identified. Since CL has been shown to be
      transcribed, the results imply the lack of the gene or, at least, a different
      gene copy number in the chimpanzees, and we propose that such differences may be
      relevant to the observed functional differences. We demonstrate here a strategy
      to identify critical genes responsible for disease development.

PMID- 8307786
TI  - Histocompatibility matching for bone marrow transplantation. Donor-recipient
      pairs in the 4AOHW cell panel.
AB  - While the results of unrelated bone marrow transplantation are continually
      improving, a number of important issues remain: what are the histocompatibility
      requirements, what genes are involved, what mismatches are acceptable, and what
      are the best methods for determining donor-recipient match? In this study of
      material provided through the 4AOHW and the US NMDP, the match between 53 donor
      recipient pairs was determined using several different markers within the MHC.
      The data showed that many apparently well-matched pairs have many mismatches,
      including mismatches for non-HLA genes (i.e., non-class-I or non-class-II) within
      the MHC. New methods matching for blocks of DNA around HLA-B and around HLA-DR/DQ
      are available that are sensitive and identify additional mismatches that are not
      apparent using conventional typing methods. The 4AOHW cells provide a valuable
      resource for the comparison and assessment of new matching techniques.

PMID- 8307787
TI  - Typing of 4AOHW cells by allospecific natural killer cells.
AB  - Alloreactivity of human NK cells was tested on a subset of the 4AOHW cell panel.
      A total of 37 cells were typed with NK clones reactive with the NK-1, 2, 3, and 5
      allospecificities. No cell was susceptible to lysis by both by anti-NK-1 and anti
      NK-2 clones in accordance with the notion of a biallelic system, where the
      susceptibility toward lysis is a recessive trait. HLA homozygous cells were lysed
      either by the anti-NK-1 or anti-NK-2 clones while HLA heterozygous cells in some
      cases were not lysed by either clone. Negativity for the NK-1 specificity
      corresponded to the presence of asparagine and lysine at positions 77 and 80,
      respectively, in the second exon of HLA-C (alleles Cw2, 4, 5, and 6), while
      negativity for the NK-2 group corresponded to the presence of serine and
      asparagine, respectively, at these two positions (alleles Cw1, 3, 7, and 8). Too
      few cells were typed with clones reactive with the NK-3 and NK-5 specificities to
      enable an analysis of correlation between these specificities and HLA alleles.

PMID- 8307788
TI  - A region centromeric of the major histocompatibility complex class I region is as
      highly polymorphic as HLA-B. Implications for recombination.
AB  - Two hallmarks of the MHC are the high degree of polymorphism apparent at multiple
      loci and "linkage disequilibrium." The data presented here suggest that a
      consequence of selection at a particular locus may be the inhibition of
      recombination through the accumulation of DNA sequence polymorphisms. Equivalent
      6.4 kb regions from a locus, CL1, located approximately 25-30 kb centromeric of
      HLA-B, were sequenced for three ancestral haplotypes: A1,B8,DR3; A30,B18,DR3; and
      A1,B57,DR7. Comparison of the sequences indicated that the level of DNA sequence
      polymorphism was high when compared with the TNF region; approximately 80 single
      nucleotide differences were found when comparing any two sequences. In addition,
      multiple deletions/insertions were present. We believe that the degree of
      polymorphism within the CL interval may be adequate to at least partially inhibit
      recombination between the haplotypes studied.

PMID- 8307789
TI  - Re-examining the use of pulmonary function tests in treatment of acute asthma
      patients.

PMID- 8307790
TI  - No 'paradigm shift' needed at COMs.

PMID- 8307791
TI  - Literature on pulmonary diseases.
AB  - The following annotated bibliography has been developed for the purpose of
      providing primary care physicians with a handy source of review articles in the
      field of pulmonary diseases. Almost all of the articles are review articles of
      clinical topics that will be of interest to the practicing physician. JAOA will
      be publishing additional annotated bibliographies in various fields of internal
      medicine over the next several months.

PMID- 8307792
TI  - Focused goals of osteopathic medical education achieve results.

PMID- 8307793
TI  - History of osteopathic medical education accreditation.

PMID- 8307794
TI  - Undergraduate osteopathic medical education.

PMID- 8307795
TI  - Financial assistance resources for osteopathic medical students.

PMID- 8307796
TI  - Income and expenditures of osteopathic medical colleges.

PMID- 8307797
TI  - Osteopathic graduate medical education. Division of Postdoctoral Training of the
      American Osteopathic Association.

PMID- 8307798
TI  - Research programs of the AOA and their role in osteopathic medical education.

PMID- 8307799
TI  - AOA continuing medical education.

PMID- 8307800
TI  - Important characteristics of a director of medical education.
AB  - In osteopathic graduate medical education programs, the Director of Medical
      Education (DME) plays the key leadership role. This article outlines critical
      characteristics and skills that the DME should possess to successfully perform in
      this role. Central to this success is a passionate commitment to osteopathic
      medical education and a commitment to justice and fairness.

PMID- 8307801
TI  - Geriatric team approach scores high for healthcare.

PMID- 8307802
TI  - Research defines the hantavirus pulmonary syndrome.

PMID- 8307803
TI  - Debate continues on the call to reform the profession.

PMID- 8307804
TI  - Debate continues on the call to reform the profession.

PMID- 8307805
TI  - Debate continues on the call to reform the profession.

PMID- 8307806
TI  - Geriatric assessment teams in nursing homes: do they work?
AB  - Several studies have examined the effectiveness of geriatric assessment teams in
      outpatient and acute care settings. This project compared medical records of 69
      consecutive nursing home patients randomly assigned on arrival to team (n = 33)
      and nonteam (standard care, n = 36) conditions. Quality-of-care indices and
      healthcare service utilization were compared over a 12-month postadmission
      period. Team patients had a significantly greater number of diagnoses and
      ancillary services combined with nonsignificant trends toward decreased
      mortality, fewer emergency department visits, and fewer drugs prescribed. The
      team approach improves quality of care. Additional clinical studies evaluating
      the effectiveness of geriatric assessment teams should be made in other nursing
      homes.

PMID- 8307807
TI  - Myofascial manipulative release of carpal tunnel syndrome: documentation with
      magnetic resonance imaging.
AB  - Four patients with carpal tunnel syndrome, unresponsive to routine conservative
      care, underwent treatment with myofascial release manipulation and self
      stretching. Magnetic resonance imaging analysis of the cross-sectional area of
      the carpal tunnel and electrodiagnosis were performed before and after treatment.
      The patients improved clinically. The nerve conduction studies showed concomitant
      reduction in distal latencies or increase in motor response amplitudes. Magnetic
      resonance imaging demonstrated that the anteroposterior and transverse dimensions
      of the carpal canal significantly increased after treatment. This study
      demonstrates that the carpal canal is a distensible structure with the potential
      to yield to a relatively simple, aggressive, nonsurgical treatment for carpal
      tunnel syndrome.

PMID- 8307808
TI  - Hantavirus in the southwestern United States: epidemiology of an emerging
      pathogen.
AB  - In May of this year, an outbreak of sudden, unexplained, and highly fatal
      respiratory illness of unknown etiology was identified in the four-corners region
      of the southwestern United States. Within 3 weeks after the collaborative
      response launched by the state and local health agencies in the affected area,
      laboratory studies from the federal Centers for Disease Control and Prevention
      suggested that an acute infection with a previously unrecognized Hantavirus
      species was responsible for the reported cluster of cases. The hantavirus
      associated with this outbreak has since been isolated in tissue culture, and
      diagnostic test systems specific for the newly identified hantavirus have been
      developed. This article summarizes the history of the outbreak as experienced by
      investigators from the Arizona Department of Health Services and reviews the
      epidemiologic and clinical aspects of both the current epidemic and hantaviruses
      in general. The sudden occurrence of acute illnesses in the Southwest due to a
      previously unrecognized hantavirus reaffirms that the potential for the emergence
      of new infectious diseases exists at any place or time in the United States. The
      response to the outbreak also illustrates how community clinicians and federal,
      state, and local health agencies work together to promptly identify the emergence
      of new disease threats, rapidly determine new etiologic agents, and develop and
      swiftly implement appropriate disease prevention and control strategies.

PMID- 8307809
TI  - Hantavirus pulmonary syndrome (HPS): report of first case in Louisiana.
AB  - Since May 1993, 26 people have died of a "unique, previously unknown" viral
      illness that presents with flu-like symptoms and progresses rapidly to
      respiratory failure and death. Originally isolated in the four-corners region of
      the Southwest, the hantavirus responsible has now been isolated from patients in
      several other areas. In this article, we describe our experience with "the most
      puzzling case so far," an infection by a "cousin" of the Southwest hantaviral
      strain in a Louisiana bridgeworker. This case is unique not only because of the
      slightly different makeup of the virus, but also because of the absence of deer
      mice, the suspected carrier of the hantavirus, in the Louisiana region.

PMID- 8307810
TI  - Crafting effective internal memos.
AB  - If properly written and used, internal memoranda communicate effectively, build
      morale, and facilitate quality work in osteopathic graduate medical education
      programs. This article outlines a format and method to use internal memoranda,
      with the overall purpose being to positively contribute to the education
      programs.

PMID- 8307811
TI  - New role for food animal practitioners.

PMID- 8307812
TI  - Relationships with consultants.

PMID- 8307813
TI  - Caprine arthritis-encephalitis virus infection.

PMID- 8307814
TI  - Pet food additives.

PMID- 8307815
TI  - What is your diagnosis? Ileocecocolic intussusception.

PMID- 8307816
TI  - Compendium of chlamydiosis (psittacosis) control, 1994. National Association of
      State Public Health Veterinarians Inc.

PMID- 8307817
TI  - Employment, starting salaries, and educational indebtedness of 1993 graduates of
      US veterinary medical colleges.

PMID- 8307818
TI  - Surgical management of atypical lateral tracheal collapse in a dog.
AB  - Tracheal collapse is often diagnosed in small-breed dogs through use of
      conventional radiography or fluoroscopy, by which the dorsoventral orientation of
      the collapse can be seen. In the dog of this report, an unusual lateral form of
      tracheal collapse was diagnosed by means of bronchoscopy after multiple
      radiographic procedures had failed to define a cause for cough and dyspnea.
      Surgical reinforcement of the abnormal region of the trachea resulted in
      resolution of clinical signs and in reduction in dynamic airway collapse, which
      was documented on follow-up bronchoscopy.

PMID- 8307819
TI  - Primary right atrial chondrosarcoma in a dog.
AB  - Primary right atrial chondrosarcoma was diagnosed in a dog that had clinical
      signs of right-sided heart failure. The tumor was attached to the intra-atrial
      septum, dorsal to the septal leaf of the tricuspid valve. Tumor cells were not
      identified elsewhere.

PMID- 8307820
TI  - Reexpansion pulmonary edema after surgery to repair a diaphragmatic hernia in a
      cat.
AB  - Fulminant pulmonary edema developed after rapid lung reexpansion following
      diaphragmatic herniorrhaphy in a cat. Despite medical treatment, the cat died.
      Pulmonary edema is a potential complication of lung reexpansion achieved by
      negative intrathoracic pressure or positive-pressure ventilation. Slow expansion
      of a collapsed lung over a 12-hour period may help prevent this devastating
      complication.

PMID- 8307821
TI  - Factor IX deficiency (hemophilia B) in a family of British shorthair cats.
AB  - This report describes the clinical findings of a British shorthair cat with
      hemophilia B, the family pedigree surrounding the case, and how this disorder can
      be perpetuated in rare breeds of cats that may be inbred by necessity. Young cats
      with histories of bleeding episodes following elective or other surgical
      procedures, periodic shifting lamenesses, or the development of subcutaneous
      hematomas should be suspect for an inherited coagulation disorder. Hemophilia A
      (factor VIII deficiency) or hemophilia B (factor IX deficiency) are the most
      likely causes, although other inherited bleeding disorders also have been
      recognized in cats.

PMID- 8307822
TI  - Pantarsal arthrodesis in dogs and a cat: 11 cases (1983-1991).
AB  - Bone plates applied to the cranial surfaces of the tibia, the tarsus, and the
      metatarsus were used in 10 dogs and 1 cat that underwent pantarsal arthrodesis.
      Lengthening plates were used in 7 dogs, and 2.7- and 3.5-mm dynamic compression
      plates were used in the remaining dogs and the cat. Radiography was used to
      determine whether bone plates became loose or broke, and whether the joint fused
      completely. Bone plates became loose in 5 dogs; mean time between surgery and
      development of radiographic evidence of plate loosening was 19.4 months. The bone
      plate used in the cat broke 4 months after surgery. Overall, 9 of 11 animals had
      evidence of complete bony fusion of the tarsus at the time of the last
      radiographic evaluation. One dog had incomplete healing of the
      talocalcaneocentral joint and another dog had incomplete healing of the
      tarsometatarsal joint.

PMID- 8307823
TI  - Immunocytochemical and dye distribution studies of nerves potentially
      desensitized by injections into the distal interphalangeal joint or the navicular
      bursa of horses.
AB  - To determine whether the distal interphalangeal (DIP) joint directly or
      indirectly communicates with the navicular bursa (bursa podotrochlearis) and to
      identify sensory nerves in these synovial structures that might be desensitized
      by intra-articular injections of anesthetics, Evans blue dye in physiologic
      saline solution, Luxol fast blue dye with mepivicaine, or commercial latex was
      injected into the DIP joint (5 ml) or the navicular bursa (3 ml) of 152 digits
      obtained from horses or ponies at necropsy. The digits were frozen, cut with a
      band saw, and examined for distribution of dye or latex. Of 122 digits that had
      injections into the DIP joint, 120 did not have evidence of a communication
      between the DIP joint and either the navicular bursa or digital flexor tendon
      sheath. Of 16 digits that had injections into the navicular bursa, 14 did not
      have evidence of a direct communication with the DIP joint. Injection of dye into
      the DIP joint resulted in diffusion of dye and staining of other structures,
      including the synovial linings of the collateral sesamoidean ligaments and of the
      distal sesamoidean impar ligament and the medullary cavity of the navicular bone.
      In addition, a blue tinge was observed in the navicular bursa after dye was
      injected into the DIP joint, suggesting an indirect, and potentially functional,
      communication between the DIP joint and the navicular bursa. Injection of dye
      into the navicular bursa resulted in staining only of the bursa's synovial
      lining. Immunocytochemical analysis revealed nerves immunoreactive for the
      peptidergic neurotransmitters substance P, and calcitonin gene-related peptide
      located in structures that were stained after dye was injected into the DIP
      joint.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307824
TI  - Diagnosis of EDTA-dependent pseudothrombocytopenia in a horse.
AB  - Thrombocytopenia in horses may be idiopathic or secondary to chronic infectious
      or inflammatory diseases (eg, equine infectious anemia, lymphosarcoma), drug
      administration, bone marrow depression, myelophthisic disease, or disseminated
      intravascular coagulation. This report describes EDTA-dependent
      pseudothrombocytopenia in a horse. Platelet counts for blood containing EDTA were
      consistently less than reference range, but platelet counts of blood containing
      heparin were within reference range. When thrombocytopenia is diagnosed in horses
      without clinical evidence of a bleeding tendency, EDTA-dependent
      pseudothrombocytopenia should be considered. The diagnosis can be confirmed
      simply by screening blood films for platelet clumps and by comparing platelet
      counts of paired blood samples, one containing EDTA and the other containing
      heparin.

PMID- 8307825
TI  - Rabies surveillance in the United States during 1992.
AB  - In 1992, 49 states, the District of Columbia, and Puerto Rico reported 8,644
      cases of rabies in nonhuman animals and 1 case in a human being to the Centers
      for Disease Control and Prevention. Almost 92% (7,912 cases) were wild animals,
      the largest number of wild animals ever reported, whereas 8.5% (732 cases) were
      domestic species. The total number of reported cases increased 23.9% over that of
      1991 (6,975 cases), with most of the increase resulting from continued spread of
      rabies in raccoons. The 2 epizootics of rabies in raccoons (Northeastern/mid
      Atlantic region and Southeastern region) are now approaching convergence in North
      Carolina (49 reported cases of rabies in 1992). Massachusetts (57 cases), New
      York City (41 cases), and New Hampshire (10 cases) became new additions to the
      epizootic in the Northeast, with Maine, Rhode Island, and Vermont the only states
      in the region without cases associated with the raccoon strain of rabies. The
      state of New York (including New York City) reported 1,761 cases (79% in
      raccoons) of rabies, the largest number ever recorded for any state. Increases
      attributable to epizootics of rabies in other species were reported by Alaska (25
      cases in 1992, compared with 12 in 1991, mainly attributable to rabies in foxes)
      and Kansas (374 cases in 1992, compared with 63 in 1991, mainly attributable to
      rabies in skunks). Reported cases of rabies in coyotes (75) increased 50% over
      those for 1991 (50 cases). In the southern portion of Texas (reporting 70 of the
      75 cases in coyotes), there was a similar increase (55%) in reported cases of
      rabies in dogs, whereas nationally, reported cases of rabies in dogs (182)
      increased 17%. Twenty states, the District of Columbia, and Puerto Rico reported
      decreases in rabies in animals in 1992, compared with 16 states in 1991. Hawaii
      was the only state that did not report a case of rabies in 1992.

PMID- 8307826
TI  - Use of prostaglandin products by dairy cattle owners, beef cattle owners, and
      veterinarians.
AB  - Questionnaires regarding the use of prostaglandin F2 alpha and its analogues
      (hereafter referred to as PG) were sent to 332 Alabama beef cattle owners and to
      279 Alabama dairy cattle owners after attempting to contact them by telephone to
      request their participation in the survey. Questionnaires concerning the use of
      PG in their clients' herds were likewise sent to 147 food animal and mixed animal
      practitioners in Alabama after attempting telephone contact. Response among beef
      cattle owners, dairy cattle owners, and veterinarians to whom questionnaires were
      mailed was 64.5, 61.6, and 75.5%, respectively. Only 7.4% (13 of 175) of
      respondent beef cattle owners reported use of PG in their herds, and this use was
      predominantly for artificial insemination and embryo transfer. In contrast, 66.5%
      (109 of 164) of respondent dairy cattle owners reported use of PG, generally with
      satisfactory results, for some of the following conditions: unobserved estrus (n
      = 77), uterine infections (n = 74), retained placenta (n = 65), cystic ovaries (n
      = 56), estrus synchronization (n = 45), and induction of parturition (n = 13).
      Although 94.9% of respondent veterinarians treated cattle with PG, those
      attending beef herds thought that more important strategies were available for
      improvement of beef cattle productivity than increased use of PG. Among these
      strategies were shorter calving seasons, improved nutrition, better record
      keeping, more frequent herd health visits, improved animal identification, and
      increased use of bull breeding soundness examinations.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8307827
TI  - Treating chronic food refusal in young children: home-based parent training.
AB  - We evaluated the effects of behavioral parent training program on parent and
      child feeding-related behaviors in the home. We trained mothers to initiate
      regular offerings of previously rejected (target) foods and to provide contingent
      attention (i.e., specific prompts, positive reinforcement) to increase their
      child's acceptance of nonpreferred foods. For 1 subject, we also directed
      training at increasing self-eating. Results of a nonconcurrent multiple baseline
      design across 3 mother-child dyads demonstrated that, with training, all mothers
      increased offerings of target foods and use of specific prompts, and 2 mothers
      increased levels of positive attention. In turn, children increased their
      acceptance of target foods and self-eating, thus demonstrating the functional
      effects of parent training on in-home meal times. Temporary increases in food
      refusals occurred when treatment was initiated but declined as treatment
      continued. We discuss the results in terms of the potential benefits and
      limitations of a home-based treatment model.

PMID- 8307828
TI  - Increasing calorie consumption in children with cystic fibrosis: replication with
      2-year follow-up.
AB  - Three mildly malnourished children with cystic fibrosis and their parents
      participated in a behavioral group-treatment program that focused on promoting
      and maintaining increased calorie consumption. Treatment included nutritional
      education, gradually increasing calorie goals, contingency management, and
      relaxation training, and was evaluated in a multiple baseline design across four
      meals. Children's calorie intake increased across meals, and total calorie intake
      was 32% to 60% above baseline at posttreatment. Increased calorie consumption was
      maintained at the 96-week follow-up (2 years posttreatment). The children's
      growth rates in weight and height were greater during the 2 years following
      treatment than the year prior to treatment. Increases in pace of eating and
      calories consumed per minute were also observed 1 year posttreatment. These
      findings replicated and extended earlier research supporting the efficacy of
      behavioral intervention in the treatment of malnutrition in children with cystic
      fibrosis.

PMID- 8307829
TI  - Empirically derived injury prevention rules.
AB  - This study describes a set of empirically derived safety rules that if followed,
      would have prevented the occurrence of minor injuries. Epidemiologists have
      criticized behavioral interventions as increasing "safe" behavior but failing to
      demonstrate a decrease in injury. The present study documents retrospectively the
      link between safe behavior and injury. It demonstrates that these empirically
      derived rules are very similar to rules for the prevention of serious injury. The
      study also shows that these rules are not widely accepted and implemented by
      parents. Suggestions for future research in this area are advanced.

PMID- 8307830
TI  - An appointment-keeping improvement package for outpatient pediatrics: systematic
      replication and component analysis.
AB  - Child health-care appointments that are not kept are an important pediatric
      problem. Previous research has shown that reducing effort (with a parking pass)
      and reminding patients (with mailed and telephone reminders) significantly
      improved appointment keeping for first-time and patient-scheduled appointments.
      This study, using a posttest-only group design, evaluated the effects of various
      combinations of that intervention applied to clinic-scheduled follow-up
      appointments. All combinations of the intervention significantly increased
      cancellations, but none increased appointments kept or decreased appointments not
      kept significantly. Log linear analyses showed that the lag time between
      scheduling and the appointment significantly influenced appointment keeping. The
      results suggest that if clinics want to increase cancellations, a mailed reminder
      and effort reduction are sufficient. To increase appointment keeping, other
      interventions, such as reduced lag time, may be necessary.

PMID- 8307831
TI  - Behavior analysis of motion control for pediatric neuroimaging.
AB  - Magnetic resonance imaging is a promising technological advance used for research
      and diagnosis of disease. The procedure has no risks, except when uncooperative
      patients require sedation. Four normal children participated in simulated scans
      to study the effects of (a) antecedent changes in the imaging environment and (b)
      operant conditioning of movement inhibition. Changing the environment can
      decrease movement, but operant contingencies were necessary to decrease movement
      to a level that, in most cases, would allow the procedure to occur without
      sedation.

PMID- 8307832
TI  - Changing protective and risky behaviors to prevent child-to-parent transmission
      of cytomegalovirus.
AB  - Child-to-parent transmission of cytomegalovirus may be reduced by increasing
      protective behaviors (handwashing and glove use) and decreasing risky behaviors
      (intimate contact between child and parent). This study showed that an
      educational intervention resulted in increases in reported and objective measures
      of protective behaviors and decreases in reported risky behaviors. Further study
      must determine if changes in protective and risky behavior are maintained and
      prevent cytomegalovirus transmission.

PMID- 8307833
TI  - A water-prompting procedure for the treatment of urinary incontinence.
AB  - Based on clinical observations of a naturally occurring phenomenon, a water
      prompting procedure was used to facilitate toilet training with a 9-year-old boy
      with profound mental retardation. Other frequently used toilet-training
      procedures were either ineffective or were associated with increased self-injury.
      The water-prompting treatment package may increase continence by eliciting and
      reinforcing urination under specific stimulus conditions.

PMID- 8307834
TI  - A brief component analysis of potential treatment packages in an outpatient
      clinic setting with young children.
AB  - The purpose of this study was to develop outpatient clinic assessments that
      allowed us to assess multiple treatment variables, produce relatively quick
      effects, and isolate active treatment components. Assessment began by evaluating
      a treatment package consisting of antecedent and consequence variables followed
      by a component analysis to determine the separate effects of the treatment
      variables. Three examples of the findings are presented.

PMID- 8307835
TI  - A behavioral model of infant sleep disturbance.
AB  - Chronic sleep disturbance, such as bed refusal, sleep-onset delay, and night
      waking with crying, affects 15% to 35% of preschool children. Biological factors,
      particularly arousals associated with recurrent episodes of rapid-eye-movement
      sleep, render infants vulnerable to repeated awakenings. Parental failure to
      establish appropriate stimulus control of sleep-related behaviors and parent
      mediated contingencies of reinforcement for sleep-incompatible behaviors may
      shape and maintain infant sleep disturbance. Treatment and prevention strategies
      are discussed, and research needs are identified.

PMID- 8307836
TI  - A behavioral prescription for promoting applied behavior analysis within
      pediatrics.
AB  - In recent decades, pediatric medicine has undergone a shift in focus from
      infectious diseases to the effects of behavior on the health and development of
      children. At the same time, behavior analysts have increasingly evaluated the
      direct application of their technology to the development and maintenance of
      child health behavior. Unfortunately, applied behavior analysts have developed
      their technology parallel to, rather than collaboratively with, pediatricians
      and, as a result, are not recognized as experts in the treatment of child health
      behavior. In addition, behavioral technology is not widely recognized as the
      treatment of choice by pediatricians. This paper provides a behavioral
      prescription for behavior analysts who wish to enter pediatrics as expert
      scientists and technicians. Specific recommendations are provided for stimulating
      collaborative rather than parallel development between applied behavior analysis
      and pediatrics in the promotion and maintenance of child health behavior.
      Strategies for maintaining this collaborative relationship and for strengthening
      the social relevance of behavior analysis are discussed.

PMID- 8307837
TI  - On systems analysis in autism intervention programs.
AB  - Although intervention technology has grown substantially during the past quarter
      century, the design of intervention systems has not grown apace. This paper
      examines organizational arrangements that enhance and diminish treatment
      effectiveness and argues that defining, measuring, and manipulating systemic
      antecedent and consequent variables are as important as assessment and
      intervention on an individual client's behalf.

PMID- 8307838
TI  - Creating new realities: program development and dissemination.
AB  - Program development and dissemination in human services present challenges and
      opportunities for social scientists. Over the past 27 years the Teaching-Family
      Model of group home treatment has moved from prototype development to widespread
      dissemination across North America. Reviewing concepts in industry related to
      product development and dissemination, the application of these concepts to a
      human services delivery system, and program replication and dissemination data
      offer information about how innovative human services can be widely adapted and
      adopted.

PMID- 8307839
TI  - The development of a treatment-research project for developmentally disabled and
      autistic children.
AB  - This paper describes the development and main results over the last 30 years from
      the treatment-research project with developmentally disabled (autistic) children
      in the Psychology Department at the University of California, Los Angeles (UCLA).
      Three important dimensions in treatment research are addressed. The first
      pertains to the role of serendipity or accidental discoveries, the second to the
      importance of pursuing inductive rather than theory-driven research, and the
      third to the importance of adding in a cumulative and step-wise manner to improve
      treatment adequacy. Data from various areas of treatment research have been used
      to illustrate new directions for the project. These illustrations center on early
      and successful attempts to isolate experimentally the environmental variables
      that control self-injury, failure to observe response and stimulus generalization
      with subsequent loss of treatment gains, and the main results of intensive and
      early behavioral intervention in the child's natural environment. Effective
      treatment for severe behavioral disorders is seen to require early intervention
      carried out during all or most of the child's waking hours, addressing all
      significant behaviors in all of the child's environments, by all significant
      persons, for many years.

PMID- 8307840
TI  - Amiloride inhibits arginine vasopressin-induced decrease in fetal lung liquid
      secretion.

PMID- 8307841
TI  - Amiloride inhibits arginine vasopressin-induced decrease in fetal lung liquid
      secretion.
AB  - The effects of arginine vasopressin (AVP) and amiloride were studied in 16
      unanesthetized fetal sheep (129-135 days of age) with indwelling catheters.
      Secretion was measured by an impermeant tracer technique. Control fetuses showed
      no change in lung liquid secretion over a 5-h period with an average secretion
      rate of 3.6 +/- 0.31 ml.kg-1.h-1. Infusion of AVP (23.4 +/- 2.23 mU.kg-1.min-1)
      in seven fetuses (134-140 days of age) produced significant decreases (from
      control) in the secretion rate over a 5-h period: the secretion rate decreased by
      68% in the last hour. Amiloride placed in the lung liquid during infusion of AVP,
      but after AVP effects had taken place, reversed the AVP-induced decrease in lung
      liquid secretion. AVP in conjunction with other hormones that are elevated during
      the stress of birth (epinephrine and cortisol) may be important in the removal of
      lung fluid at birth.

PMID- 8307842
TI  - Evaluation of effects of PAF on alveolar fluid clearance with use of NMR imaging.
AB  - Autologous serum with or without platelet-activating factor (PAF) was instilled
      into one lung lobe of an anesthetized cat, and changes in the regional lung water
      content were monitored for 4 h with proton nuclear magnetic resonance (NMR)
      images and relaxation time measurements. With serum as an instillate, water was
      cleared with a half time of approximately 670 min; after 4 h, 86 +/- 6% of that
      instilled remained. With PAF added to the instillate, clearance was biphasic with
      an initial clearance half time of approximately 30 min followed by clearance
      similar to that observed after serum instillation; after 4 h, 35 +/- 4% of that
      instilled remained. In contrast, 4 h after instillation of serum or serum plus
      PAF, 91 +/- 3% and 82 +/- 5%, respectively, of the instilled 125I-labeled albumin
      remained in the lung (P = 0.06). From transverse magnetization relaxation curves
      we were able to resolve two relaxation components, which we have attributed to
      the instilled fluid in the air spaces (relaxation time = 177 +/- 7 ms) and the
      tissue-bound fluid (relaxation time = 25 +/- 1 ms).

PMID- 8307843
TI  - Exposure to ozone alters regional function and particle dosimetry in the human
      lung.
AB  - Effects of experimental exposure to O3 (0.33 ppm) or filtered air on regional
      lung function were assessed in nine healthy male subjects. Immediately after 2-h
      chamber exposures, regional ventilation and particle dosimetry were measured by
      gamma camera imaging. The vertical distributions of a radiolabeled gas (133Xe)
      and aerosol (3.5-microns-diam insoluble 99mTc-tagged Fe2O3 particles) were
      quantitated for upper, middle, and lower lung regions; distribution data were
      corrected for regional differences in lung volume and tissue attenuation. Indexes
      of mechanical function, inspiratory capacity, and mid-maximal expiratory flow
      rates were significantly reduced after O3, but functional residual capacity
      remained unchanged. Exposure to O3 significantly enhanced the fraction of
      respired aerosol retained by the lung and altered the distribution pattern of
      deposited aerosol by increasing particle deposition to the middle lung region (P
      < 0.05). Aerosol penetration indexes, i.e., ratio of particle deposition in
      central lung regions to that in peripheral lung regions, and particle retention
      24 h postinhalation (an index of aerosol deposition within alveoli and slowly
      clearing bronchioles) indicated that particle filtration efficiency had increased
      for tracheobronchial and parenchymal lung regions. For seven of the nine
      subjects, regional ventilation after O3 was reduced by 14% to the lung base and
      enhanced by 8 and 6% to the upper and middle lung regions, respectively; these
      changes were significant (P < 0.02) compared with ventilation after filtered
      air.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307844
TI  - Swim training alters renal and cardiovascular responses to stress in borderline
      hypertensive rats.
AB  - The present study assessed the effects of 40 min of tail shock stress (1-s shock,
      0.2 mA every 30 s) on renal and cardiovascular function in swim-trained (T),
      water-immersed (IM), and untrained (UT) borderline hypertensive rats (BHR). T BHR
      swam for 2 h/day 5 days/wk for 10-12 wk, whereas IM BHR on the same schedule were
      placed in water at neck level and were not permitted to swim. Age-matched
      sedentary controls were paired one each with the exercise group (group 1) and the
      immersion group (group 2). Heart rate was significantly greater in UT than in T
      BHR (P = 0.09) during baseline (rest). Heart rate responses during stress were
      not different between UT and IM BHR (group 2). Systolic and diastolic blood
      pressures during stress and recovery were not different between UT BHR and T or
      IM BHR. Urine flow rate was significantly increased from baseline during the
      first 20 min of stress in UT and IM BHR only. Changes in glomerular filtration
      rate were not consistent across studies. Renal blood flow decreased significantly
      from baseline during tail shock stress in UT but not T BHR. Plasma glucose levels
      were significantly increased above baseline during the second 20 min of stress in
      UT BHR only and were significantly greater than those in the T BHR. Plasma
      insulin levels in UT BHR were significantly decreased from baseline during tail
      shock stress and recovery but were unchanged from baseline in T BHR. These
      observations suggest that swim training independent of water immersion alters the
      effect that stress exerts on renal and cardiovascular function in BHR, which
      results in better fluid and electrolyte conservation in T BHR.

PMID- 8307845
TI  - Nicotine is responsible for airway irritation evoked by cigarette smoke
      inhalation in men.
AB  - To determine whether nicotine is involved in evoking the irritant effects of
      cigarette smoke in airways, we studied the responses to inhalation of a single
      puff (30 ml) of three types of smoke (high nicotine, low nicotine, and gas phase)
      in healthy male nonsmokers. After the upper airways were locally anesthetized,
      the subjects, breathing through a mouthpiece, were instructed to signal the
      detection and the intensity of airway irritation with a push-button device.
      Inhalation of high-nicotine smoke consistently triggered an intense airway
      irritation in the lower neck and upper chest region; the total number of push
      button signals generated in the first 5 s was 6.61 +/- 0.87 (mean +/- SE, n =
      12), with a detection latency of 0.93 +/- 0.11 s. By contrast, inhalation of low
      nicotine and gas phase smoke either was not detected or caused only very mild
      irritation (0.89 +/- 0.4 and 0.36 +/- 0.22, respectively). In addition, the
      intensity of smoke-induced airway irritation was markedly reduced after
      premedication with aerosolized hexamethonium, a nicotinic receptor antagonist (P
      < 0.01, n = 8). Furthermore, inhalation of nicotine aerosol also immediately
      evoked intense airway irritation and coughs (n = 5). Thus we conclude that the
      airway irritation evoked by inhaling cigarette smoke results from an activation
      of sensory endings located in the central airways and nicotine is the primary
      agent responsible for this action.

PMID- 8307846
TI  - Faster O2 uptake kinetics at onset of supine exercise with than without lower
      body negative pressure.
AB  - The kinetics of oxygen uptake (VO2) were observed at the onset of submaximal
      cycling exercise in seven men and one woman [mean age 22.6 +/- 0.9 (SE) yr] in
      the upright and supine positions and the supine position with -40 mmHg lower body
      negative pressure (LBNP). There was no significant difference for peak VO2 and
      ventilatory threshold between the supine (3,081 +/- 133 and 1,954 +/- 138 ml/min,
      respectively) and the supine + LBNP positions (3,062 +/- 152 and 1,973 +/- 122
      ml/min); however, both were reduced compared with upright exercise (3,483 +/- 200
      and 2,353 +/- 125 ml/min). Kinetic analysis applied to six repetitions by each
      subject indicated a slowing from a mean total lag time (time required to achieve
      63% of the difference in VO2 between baseline and new steady state) of 36.3 +/-
      2.7 s in upright exercise to 44.1 +/- 3.5 s in the supine position. However,
      total lag time for the supine + LBNP position (36.0 +/- 2.8 s) did not differ
      from upright exercise but was significantly faster than supine exercise. These
      data have been interpreted in support of an O2 transport limitation to VO2
      kinetics at the onset of supine exercise that is countered by LBNP, likely
      through a more rapid increase in perfusion to the exercising muscle at these
      submaximal work rates.

PMID- 8307847
TI  - Autonomic regulation of heart rate response to exercise in Tibetan and Han
      residents of Lhasa (3,658 m).
AB  - To test the hypothesis that native high-altitude residents have less beta
      sympathetic and more parasympathetic tone than newcomers, we compared the effects
      of beta-sympathetic and parasympathetic blockade in 10 Tibetan and 9 Han
      acclimatized male residents of Lhasa, Tibet Autonomous Region, China (elevation
      3,658 m). Each subject was studied during cycle ergometer exercise at 70, 132,
      and 191 W after placebo (normal saline), beta-sympathetic (propranolol, 0.2 mg/kg
      iv), or parasympathetic (atropine, 0.04 mg/kg iv) blockade in random order on
      different days. At rest, the fall in resting heart rate with propranolol and the
      rise with atropine were equal in Tibetan and Han subjects. During exercise, the
      fall in heart rate with propranolol relative to placebo values was greater in the
      Han than in the Tibetan group, whereas the rise in heart rate with atropine was
      greater in the Tibetans. Propranolol or atropine administration did not change
      minute ventilation per unit O2 consumption in either group. At the highest level
      of exercise on the placebo day, the Tibetans achieved a higher work load and
      level of O2 consumption than the Han subjects. Propranolol or atropine reduced O2
      consumption and work load similarly in the two groups at the highest exercise
      level. The results supported our hypothesis that native Tibetan residents of high
      altitude exhibit more para-sympathetic and less beta-sympathetic tone during
      exercise. Neither relatively greater parasympathetic nor less sympathetic
      activation appeared implicated in the greater exercise capacity of Tibetans
      compared with that of acclimatized newcomer residents of high altitude.

PMID- 8307848
TI  - Lactate turnover at rest and during submaximal exercise in patients with heart
      failure.
AB  - Systemic and lower limb skeletal muscle lactate metabolism was studied in 10 men
      with congestive heart failure by use of a primed continuous intravenous infusion
      of L-(+)-[U-14C]lactate. Arterial and deep femoral venous blood samples were
      obtained at rest and during 30 min of submaximal exercise. Systemic lactate
      metabolic turnover rate (Rd) was determined using Steele's isotopic steady-state
      equation (Rd = isotopic infusion rate/arterial specific activity). Plasma lactate
      concentrations in the artery and deep femoral vein did not change significantly
      from resting values during exercise (1.11 +/- 0.13 vs. 1.26 +/- 0.12 and 1.27 +/-
      0.12 vs. 1.30 +/- 0.12 mM, respectively), whereas Rd increased from 22.5 +/- 1.8
      to 41.6 +/- 4.8 mumol.kg-1.min-1 (P < 0.005). Rd did not significantly correlate
      with arterial lactate concentration during rest or exercise. Because of
      simultaneous uptake and release of lactate in skeletal muscle, arterial and deep
      femoral venous lactate concentrations are not closely related to either systemic
      or lower limb skeletal muscle lactate metabolism in patients with congestive
      heart failure.

PMID- 8307849
TI  - Effect of humidity on hyperoxic toxicity.
AB  - Time to onset of hyperbaric oxygen-induced convulsions was measured in mice and
      rats exposed to hyperbaric oxygen (515-585 kPa) under conditions of low humidity
      (dry gas, < 10% relative humidity) or in a humidified environment (60% relative
      humidity). At all pressures tested, the duration of convulsive activity was
      markedly increased (P < 0.001), because of the earlier onset of severe
      generalized convulsions, in the groups of rodents exposed to the higher humidity.
      Pulmonary oxygen poisoning was determined by increases in lung wet and dry
      weights. Such pulmonary damage was also significantly (P < 0.001) increased in
      the humidified groups. Hyperoxic toxicity was also measured in rats and mice
      exposed to approximately 100% oxygen (normobaric hyperoxia) under conditions of
      30 or 62% relative humidity. In contrast to the results obtained with hyperbaric
      oxygen exposure, there was slightly less toxicity in the rodents maintained at
      62% compared with 30% humidity in normobaric hyperoxia.

PMID- 8307850
TI  - Contribution of vasopressin to blood pressure regulation during hypovolemic
      hypotension in humans.
AB  - In animals subjected to hemorrhage, plasma arginine vasopressin concentrations
      increase to levels sufficient to cause vasoconstriction, thus attenuating the
      hypotensive response. The purpose of this study was to examine the contribution
      of vasopressin to blood pressure regulation during hypotension in humans.
      Hypotension was induced in twelve normal subjects by lower body negative pressure
      (LBNP) before and after intravenous administration of vasopressin V1 receptor
      antagonist. Before drug administration, LBNP reduced systolic blood pressure from
      125 +/- 4 to 78 +/- 12 mmHg (P < 0.01) as vasopressin concentration increased
      from 2.9 +/- 0.6 to 17 +/- 6 pg/ml (P < 0.05). After administration of the
      vasopressin antagonist, LBNP reduced systolic blood pressure from 128 +/- 3 to 89
      +/- 11 mmHg (P < 0.01). The hypotensive response to LBNP was not potentiated by
      inhibiting vasopressin's vasoconstrictive effects (P = NS). Thus hypotension
      causes marked increases in plasma vasopressin concentration. In contrast to
      findings in animal studies, however, vasopressin does not contribute to the
      maintenance of blood pressure during hypotension in humans.

PMID- 8307851
TI  - Left ventricular function during dynamic exercise in untrained and moderately
      trained subjects.
AB  - The influence of exercise training on left ventricular function at rest (R), at
      anaerobic threshold (AT), and during peak exercise (PE) was evaluated in 12
      healthy untrained and 13 trained (T) subjects who underwent Doppler
      echocardiography at R and radionuclide ventriculography at R and during exercise.
      The end-diastolic volume and stroke volume were significantly higher in the T
      group than in the untrained group at R. The ejection fraction rose significantly
      from R to AT and from AT to PE (80.0 +/- 0.84 vs. 83.6 +/- 0.91%), but no
      significant difference was observed between groups. The peak diastolic filling
      rate rose significantly during exercise, with a further significant increase
      observed in the T group (AT, 6.38 +/- 0.40 vs. 5.01 +/- 0.16 end-diastolic
      counts/s; PE, 8.24 +/- 0.42 vs. 7.15 +/- 0.35 end-diastolic counts/s). The
      percent variation of minimal systolic counts fell significantly at AT and PE in
      relation to R. Our data demonstrate that exercise training produces a significant
      increase in peak diastolic filling rate but no change in systolic function during
      exercise and that metabolic acidosis caused by exercise does not limit systolic
      function.

PMID- 8307852
TI  - Interactive effect of inhaled bradykinin with histamine and PGD2 in bronchial
      asthma.
AB  - Interaction among mediators such as bradykinin (BK), histamine (H), and
      prostaglandin (PG) D2 may contribute to reduction in airway caliber in asthma.
      Ten stable asthmatic subjects took part in a study to investigate possible
      mediator interaction. The provocative concentration of mediator required to
      reduce forced expiratory volume in 1 s (FEV1) by 12.5% from the starting baseline
      value (PC12.5) and that required to reduce the fall in FEV1 from 12.5 to 25%
      (PC25-12.5) of H, BK, and PGD2 were determined. On three subsequent occasions,
      subjects inhaled either the vehicle plus BK PC12.5 or the vehicle plus H or PGD2
      PC25-12.5, and FEV1 was measured at regular time intervals up to 40 min.
      Predicted time course curves were calculated from these results. On two
      additional occasions, interactive time course studies were undertaken when the
      subject inhaled BK PC12.5 followed by H or PGD2 PC25-12.5. On a further three
      visits, the time courses of individual mediators were studied. When BK was
      combined with H and PGD2, the maximum fall in FEV1 and the rate of recovery after
      inhalation of the second mediator were not significantly different from those
      values of predicted time course responses for the same combination of mediator.
      Thus, by employing pharmacologically active concentrations of inhaled BK, H, and
      PGD2, which act through separate receptor mechanisms, we were unable to
      demonstrate any pharmacological interaction on airway caliber in asthma.

PMID- 8307854
TI  - Relevance of classification by size to topographical differences in bronchial
      smooth muscle response.
AB  - To investigate heterogeneity of airway smooth muscle response, we studied strips
      of large and small branches from third- to sixth-generation bronchi obtained from
      ragweed antigen-sensitized and control dogs. The response to electrical field
      stimulation and carbamylcholine chloride was greater in strips from larger
      branches of the same generation when expressed as "tissue stress" (force per unit
      cross-sectional area of the whole tissue), whereas no difference emerged with use
      of the more appropriate "smooth muscle stress" (force per unit cross-sectional
      area of the muscle tissue). The response to histamine was significantly higher in
      small branches than in large ones, and histamine sensitivity [mean effective
      concentration (EC50)] was 7.79 x 10(-6) [geometric standard error of the mean
      (GSEM) 1.20] and 1.49 x 10(-5) M (GSEM 1.14), respectively (P < 0.01). Strips
      from control and sensitized animals at each site and strips from different
      generations did not show any significant difference. When we clustered our
      preparations according to dimensions, the response to histamine was significantly
      higher in small bronchi than in large ones and histamine EC50 was 8.95 x 10(-6)
      (GSEM 1.17) and 1.57 x 10(-5) M (GSEM 1.18), respectively (P < 0.05). We conclude
      that evaluation of muscle response in different tissues requires appropriate
      normalization. Furthermore, classification into generations is inadequate to
      study bronchial responsiveness, inasmuch as major differences originate from
      airway size.

PMID- 8307853
TI  - Adaptive buffering of breath-by-breath variations of end-tidal CO2 of humans.
AB  - We have designed and implemented a computer-controlled system that uses an
      adaptive control algorithm (generalized minimum variance) to buffer the breath-by
      breath variations of the end-tidal CO2 fraction (FETCO2) that occur spontaneously
      or are exaggerated in certain experimental protocols (e.g., induced hypoxia, any
      type of induced variations in the ventilatory pattern). Near the end of each
      breath, FETCO2 of the following breath is predicted and the inspired CO2 fraction
      (FICO2) of the upcoming breath is adjusted to minimize the difference between the
      predicted and desired FETCO2 of the next breath. The one-breath-ahead prediction
      of FETCO2 is based on an adaptive autoregressive with exogenous inputs (ARX)
      model: FETCO2 of a given breath is related to FICO2, FETCO2 of the previous
      breath, and inspiratory ventilation. Adequacy of the prediction is demonstrated
      using data from experiments in which FICO2 was varied pseudorandomly in
      wakefulness and sleep. The algorithm for optimally buffering changes in FETCO2 is
      based on the coefficients of the ARX model. We have determined experimentally the
      frequency of FETCO2 variations that can be buffered adequately by our controller,
      testing both spontaneous variations in FETCO2 and variations induced by hypoxia
      in young awake human subjects. The controller is most effective in buffering
      variations of FETCO2 in the frequency range of <0.1 cycle/breath. Some potential
      applications are discussed.

PMID- 8307855
TI  - Chemical and nonchemical stimuli during breath holding in divers are not
      independent.
AB  - In the breath-hold model described by S. Godfrey and E. J. M. Campbell (Respir.
      Physiol. 5: 385-400, 1968), chemical and nonchemical stimuli are independent.
      Because these two factors are time dependent, the effect of each could not be
      measured by breath-holding time (BHT). The aim of this study is to dissociate
      chemical and nonchemical stimuli and to assess the effects of BHT and PCO2 on
      respiratory center output by measurement of occlusion pressure (P0.1) and mean
      inspiratory flow (VI). Nine well-trained divers (age 36.5 +/- 5.0 yr) took part
      in the study. Each subject had to hold his breath at 75% of vital capacity for
      30, 50, and 70 s of BHT. Before each breath hold, the subject inspired
      successively two vital capacities of the same CO2-O2 gas mixture. P0.1 and VI
      were measured during the first reinspiration after the breath hold. For the same
      BHT, we observed good linear relationships between P0.1 or VI and alveolar PCO2.
      The slopes of these relationships increased with BHT. For alveolar PCO2 of > 50
      Torr, P0.1 increased linearly with BHT. These results indicate that, during
      breath holding, chemical and nonchemical stimuli acted linearly on respiratory
      motoneuron activity, but they were not independent.

PMID- 8307856
TI  - Spreading of exogenous surfactant in an airway.
AB  - Using a theoretical model, we studied spreading of a bolus of insoluble
      surfactant deposited on a thin liquid layer of a model airway. Applications
      include instillation of exogenous surfactant as a treatment for neonatal
      respiratory distress syndrome, the use of surfactant carriers to deliver drugs
      via the lung, and the movement of liquid along the airway tree due to naturally
      occurring gradients of surface tension. The time-dependent governing equations
      were solved numerically for longitudinal axisymmetric surfactant spreading. We
      examined the influences of the resident liquid layer (thickness, viscosity,
      endogenous surfactant, airway radius), of the bolus (volume and surfactant
      content), and of gravity. The gradient in surface tension drives the flow toward
      the region of higher surface tension, ultimately creating a shocklike wave of
      nearly twice the initial lining thickness. Pressure gradients due to interfacial
      curvature (capillarity) have little effect on the rate of surfactant spread. The
      presence of an endogenous resident surfactant greatly augments the rate of
      spreading while inhibiting development of the shock. In all cases studied, the
      effect of circumferential curvature was negligible, indicating that the liquid
      layer can be treated as if it were spreading over a flat surface. Our results
      reveal that the surfactant spreads as time to the one-third power. Accordingly, a
      surfactant deposited in the trachea of a neonate would spread to the periphery in
      approximately 12 s.

PMID- 8307857
TI  - Maximum discharge rates of respiratory neurons during opossum development.
AB  - The observed low frequencies of action potentials observed in medullary
      respiratory neurons of immature opossums (Didelphis virginiana) could occur
      because these cells are incapable of achieving higher sustained firing rates.
      Nonsustainability of firing might also help explain why the inspired breath is
      brief (approximately 0.1 s) in the youngest opossums and rises very slowly during
      postnatal life. Firing frequencies of medullary respiratory neurons were examined
      in spontaneously breathing thiobarbiturate-anesthetized opossums before and after
      stimulation by the glutamate agonists, N-methyl-D-aspartate (NMDA; 20 mM) or
      kainic acid (KA; 0.5 mM). Drugs were applied using progressively larger pressure
      injections through a micropipette; animals were tested from the 5th postnatal wk
      to adulthood. With a sufficient injection volume, stimulation of cell firing
      would be followed by apparent suppression of action potentials. A maximum
      "sustained" firing frequency was obtained from the last injection where discharge
      remained elevated for at least 0.5 s. Inspiratory and expiratory neurons tested
      with either drug showed the lowest rates of firing in opossums at 5-9 wk of age
      compared with 10- to 14-wk-old animals and/or adults. Despite higher rates of
      discharge in 10- to 14-wk-old animals and/or adults, maximum sustained neuronal
      firing in the youngest animals was at a higher frequency than during spontaneous
      breathing and, at least in the cell population tested, does not represent a
      limitation that might affect breathing pattern.

PMID- 8307858
TI  - Growth of airways and air spaces in teenagers is related to sex but not to
      symptoms.
AB  - To determine growth patterns of the lung and airways in adolescents, we analyzed
      maximal expiratory flow-volume curves, closing capacity, and residual volume.
      They were obtained every 6 mo for up to 7 yr in 430 boys and 125 girls (11-19
      yr), of whom 143 boys and 36 girls were classified as symptomatic; symptoms were
      most often minor and limited to childhood. Development of flows vs. volumes was
      used to investigate growth of the airways relative to lung size. A model of
      isotropic growth of the airways and air spaces (J. Appl. Physiol. 65: 822-828,
      1988) was modified for increasing elastic recoil pressure with growth. Growth of
      airways relative to volume occurred faster in teenage boys than in teenage girls
      and was compatible with isotropic growth in 92% of asymptomatic boys and in 44%
      of asymptomatic girls: dysanaptic growth in teenage girls seems to be a normal
      phenomenon and not a unique characteristic of symptomatic subjects. Subjects with
      respiratory symptoms in childhood and/or adolescence have lower flows for a given
      lung size and airway closure at a greater lung volume when they enter adulthood.
      However, no difference in patterns of lung growth was observed in association
      with the presence of respiratory symptoms.

PMID- 8307859
TI  - Cerebral blood flow and evoked potentials during reoxygenation with 21 or 100% O2
      in newborn pigs.
AB  - The effects of resuscitation with 21 or 100% O2 on cerebral blood flow (CBF) and
      somatosensory evoked potentials (SEPs) were studied in 19 newborn pigs
      anesthetized with pentobarbital sodium. They were ventilated with 8% O2 until
      base excess reached -20 mmol/l and then were randomly reoxygenated with 21% O2 (n
      = 10) or 100% O2 (n = 9) for 25 min followed by 21% O2. Mean duration of
      hypoxemia in the two groups was 57 +/- 6 (SE) and 59 +/- 6 min, respectively. CBF
      determined by radioactive microspheres was significantly increased in all areas
      in both groups after 5 and 20 min of reoxygenation. At 5 min of reoxygenation
      forebrain O2 uptake (CMRo2) had increased significantly compared with baseline
      values in the 21% O2 group (2.5 +/- 0.1 to 3.2 +/- 0.2 ml.100 g-1.min-1) but not
      in the 100% O2 group. There were, however, no significant differences between the
      two groups in CBF or CMRo2 at any time, and by 60 min of reoxygenation both had
      returned to baseline levels. SEPs were not significantly different in the two
      groups. We conclude that, as judged by CBF, CMRo2, and SEP, 21% O2 is not
      inferior to 100% O2 when hypoxemic newborn pigs are reoxygenated.

PMID- 8307860
TI  - Bradykinin contributes to the exercise pressor reflex: mechanism of action.
AB  - This study determined the receptors responsible for mediating bradykinin's effect
      on skeletal muscle afferents that cause the pressor reflex in anesthetized cats.
      In eight cats, 1 microgram of bradykinin was injected intra-arterially into the
      gracilis muscle before and after intravenous injection of a kinin B2-receptor
      antagonist (NPC 17731, 20 micrograms/kg). Initial injection of bradykinin
      reflexly increased mean arterial pressure by 23 +/- 7 mmHg, maximal change in
      pressure over time by 439 +/- 272 mmHg/s, and heart rate by 11 +/- 4 beats/min.
      The hemodynamic response to bradykinin was abolished by kinin B2-receptor
      blockade. Similar injection of the kinin B1-receptor agonist des-Arg9-bradykinin
      caused no cardiovascular responses (n = 6). In eight different animals, mean
      arterial pressure, maximal change in left ventricular pressure over time, and
      heart rate responses to 30 s of electrically stimulated hindlimb contraction were
      attenuated by 50 +/- 6, 55 +/- 7, and 41 +/- 8%, respectively, after kinin B2
      receptor blockade. In eight other animals, mean arterial pressure, maximal change
      in left ventricular pressure over time, and heart rate responses were reduced by
      58 +/- 8, 66 +/- 6, and 40 +/- 12%, respectively, after inhibition of
      prostaglandin synthesis with indomethacin (2.5-3 mg/kg iv) and were then
      abolished by subsequent B2-receptor blockade. These data suggest that bradykinin
      contributes to the exercise pressor reflex through its action on kinin B2
      receptors located on the nerve endings of the muscle afferents.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8307861
TI  - Thromboxane receptor stimulation/inhibition and perfusion redistribution after
      acute lung injury.
AB  - Perfusion redistribution (PR) after acute oleic acid (OA) lung injury may be the
      result of changes in the tissue concentration ratio of thromboxane (Tx) and
      prostacyclin (A. H. Stephenson et al. J. Appl. Physiol. 73: 2126-2134, 1992). We
      tested this hypothesis by determining whether the Tx mimetic U-46619 would mimic
      PR caused by cyclooxygenase inhibition with meclofenamate and whether the Tx
      receptor antagonist ONO-3708 would inhibit PR even in the presence of
      meclofenamate. Measurements of regional pulmonary blood flow (PBF) and lung water
      concentration were made with the nuclear medicine imaging technique of positron
      emission tomography. Measurements were made at baseline and 2 h after OA. At
      baseline, the spatial distribution of PBF was similar in all experimental groups.
      Two hours after OA, fractional PBF was reduced to the edematous lung in all
      groups given OA, but the magnitude of change was greater in those groups
      receiving meclofenamate or U-46619 compared with the change in the group given OA
      only. Thus, although the Tx mimetic produced the same amount of PR as
      meclofenamate, Tx inhibition did not prevent PR after meclofenamate. Therefore,
      the ratio of Tx to prostacyclin per se is not the critical determinant of PR.

PMID- 8307862
TI  - Volume changes in the legs of paraplegic subjects during arm exercise.
AB  - The purpose of this study was to examine the inability of paraplegic (P) subjects
      to redistribute fluid below the spinal cord lesion during arm exercise, with
      emphasis on the role of the sympathetic system in this redistribution failure.
      Fifteen male P and 15 male able-bodied [control (C)] subjects performed arm
      cranking exercise, and volume changes in the calf were measured by strain gauge
      plethysmography before, during, and after exercise. Muscle pump activity in the
      legs of C subjects was eliminated. The rate of calf volume decrease at the
      beginning and halfway points of the exercise period, the total volume decrease
      during exercise, and the volume increase during recovery were significantly lower
      in P than in C subjects. Whereas completeness of the lesion had no influence on
      leg volume changes, the rate of calf volume decrease at the beginning of exercise
      and the total volume decrease during exercise were significantly correlated with
      the level of the spinal cord lesion. This study confirms that P subjects are
      unable to redistribute fluid effectively below the spinal cord injury during arm
      exercise, which is partly caused by a loss of sympathetically induced
      vasoconstriction and which appears to be independent of the completeness of the
      lesion but dependent on its level.

PMID- 8307863
TI  - Tracheal and neck position influence upper airway airflow dynamics by altering
      airway length.
AB  - Upper airway obstruction during sleep is characterized by inspiratory airflow
      limitation and reductions in maximal inspiratory airflow (VImax). To determine
      how mechanical factors modulate VImax, we analyzed pressure-flow relationships
      obtained in the isolated upper airway of paralyzed cats. VImax and its
      determinants, the pharyngeal critical pressure (Pcrit) and the nasal resistance
      (Rn) upstream to the flow-limiting site (FLS), were measured as caudal tracheal
      displacement, neck position, and airway length were systematically varied. As the
      proximal tracheal stump was displaced caudally, graded increases in VImax from
      145.3 +/- 90.8 (SD) to 285.9 +/- 117.5 ml/s (P < 0.02) and decreases in Pcrit
      from -3.0 +/- 3.0 to -9.5 +/- 3.4 cmH2O (P < 0.002) were seen without any
      significant change in Rn. During neck flexion, significant decreases in VImax
      from 192.1 +/- 68.5 to 87.2 +/- 48.4 ml/s (P = 0.001), increases in Pcrit from 
      5.3 +/- 2.03 cmH2O to -1.6 +/- 1.4 cmH2O (P < 0.001), and decreases in Rn from
      29.7 +/- 12.2 cmH2O.l-1.s to 16.2 +/- 8.9 cmH2O.l-1.s (P < 0.001) were noted
      compared with the neutral or extended neck position. Relative to the neutral
      airway length, upper airway length was found to decrease by 1.15 +/- 0.14 cm
      during neck flexion and to lengthen by 0.45 +/- 0.12 cm during neck extension.
      When tracheal displacement and neck position were altered, VImax and Rn
      correlated directly and Pcrit correlated inversely with airway length (P <
      0.001). We conclude that alterations in airflow mechanics with caudal tracheal
      displacement and changes in neck positions are primarily due to alterations in
      airway length.

PMID- 8307864
TI  - Effects of respiratory afferent stimulation on phrenic neurogram during hypoxic
      gasping in the cat.
AB  - Previous studies suggested that phrenic motor output is largely refractory to
      afferent stimuli during gasping. We tested this concept by electrically
      stimulating the carotid sinus nerve (CSN) or the superior laryngeal nerve (SLN)
      of anesthetized peripherally chemodenervated vagotomized ventilated cats during
      eupnea or gasping induced by hypoxia. During eupnea, phrenic neurogram amplitude
      (PNA) increased by 110% during 30 s of supramaximal CSN stimulation, but burst
      frequency did not change. Progressive hypoxia caused gasping after arterial O2
      content was reduced by 75%. During gasping, CSN stimulation caused premature
      onset of gasp in 12 of 13 trials, shortened intergasp interval [6.3 +/- 0.9 vs.
      14.8 +/- 2.5 (SE) s], and resulted in a small (20%) but significant increase in
      PNA. Intensity of SLN stimulation was adjusted to abolish phrenic activity during
      the 30-s eupneic stimulation period. During gasping, SLN stimulation of the same
      intensity tended to delay onset of the next gasp, increased intergasp interval
      (16.9 +/- 1.9 vs. 13.3 +/- 1.2 s), and reduced PNA by 32%. Thus the respiratory
      burst pattern formation circuitry responds to afferent stimuli during gasping,
      albeit in a manner different from the eupneic response. These observations
      suggest that gasping is the output of a modified eupneic burst pattern formation
      circuit.

PMID- 8307865
TI  - Lung responses to ultrasound-guided fetal treatments with corticosteroids in
      preterm lambs.
AB  - Maternal corticosteroid treatments augment lung function in the human preterm
      infant. However, not all fetuses respond, the response requires > or = 48 h of
      exposure, and multiple maternal doses expose the mother to potential risks. To
      evaluate the potential of direct fetal therapy, we used ultrasound to direct
      fetal intramuscular or intravascular injections of corticosteroids or saline in
      sheep and subsequently delivered the preterm lambs at 128 days gestational age to
      assess postnatal lung function. Relative to saline-injected controls, 0.5 or 2
      mg/kg betamethasone given as a single intramuscular dose 48 h before delivery
      increased compliance and the efficiency of ventilation (as measured by an
      indicator that included ventilatory pressures and CO2 values) nearly twofold (P <
      0.05). Lung volumes, measured from deflation pressure-volume curves, also
      increased (P < 0.05). However, the 2 mg/kg dose caused severe pulmonary
      interstitial emphysema in 5 of 13 lambs, suggesting adverse effects. An
      intravascular fetal dose of 12.5 mg/kg hydrocortisone or an intramuscular dose of
      0.1 mg/kg betamethasone had no effect on postnatal lung function. In separate
      studies, the 2 mg/kg dose improved all indicators of lung function almost twofold
      after only 24 h of fetal exposure and delivery at 128 days gestational age (P <
      0.01). There was a dose-dependent suppression of the postnatal cortisol surge in
      treated animals, although fetal treatment did not alter cord cortisol levels.
      Single-dose fetal hormone treatments can cause large and rapid improvements in
      postnatal lung function in preterm lambs.

PMID- 8307866
TI  - Direct measurement of pulmonary microvascular distensibility.
AB  - Pulmonary vascular distensibility has an important influence on pulmonary
      hemodynamics. Although many measurements of distensibility have been made on
      large pulmonary vessels, there is less information on microvascular
      distensibility. We have measured the distensibility of the smallest (< 70-microns
      diam) precapillary arterioles and postcapillary venules. Isolated dog lobes, at
      2.5 cmH2O transpulmonary pressure, were perfused at low flows, which caused the
      arteriovenous pressure gradient to be very small and thereby permitted accurate
      estimation of microvascular pressure. As microvascular pressure was
      systematically varied between 0 and 30 mmHg, subpleural microvascular diameters
      were determined from computer-enhanced images obtained by videomicroscopy.
      Arteriolar and venular distensibilities were not different from each other. The
      microvascular pressure-diameter relationship was alinear with distensibility
      coefficients of 1-3% mmHg-1, values that are of the same order of magnitude as
      previously measured distensibilities of 100- to 1,000-microns-diam canine
      pulmonary vessels.

PMID- 8307867
TI  - Responsiveness of the guinea pig trachea to stretch: role of the epithelium and
      cyclooxygenase products.
AB  - The role of the epithelium and cyclooxygenase products was investigated in the
      responses of isolated airways to sudden stretch. Strips of guinea pig trachea, in
      some of which the epithelium had been removed mechanically, were suspended in
      organ chambers; isometric tension was recorded. After rapid stretching to their
      optimal tension, the preparations (with and without epithelium) relaxed initially
      and then contracted to a level close to the imposed tension. Afterward, tissues
      with epithelium maintained this level of tension, but those without epithelium
      relaxed. After treatment with papaverine or isoproterenol (at concentrations
      causing maximal relaxation), stretch was followed only by a decrease in tension;
      a similar response to stretch was also obtained in tissues treated with
      indomethacin or acetylsalicylic acid (inhibitors of cyclooxygenase). Dazmegrel
      (an inhibitor of thromboxane synthase) and SQ-29548 (an antagonist of
      prostaglandin H2 or thromboxane A2 receptors) did not affect the response of
      tissues with epithelium but abolished the stretch-induced contraction in those
      without epithelium. Tranylcypromine, which inhibits prostacyclin synthase, and
      tetrodotoxin, which blocks local reflexes, did not significantly affect the
      responses of the tissues to stretch. These observations suggest that thromboxane
      may mediate the epithelium-independent contraction and that another product of
      cyclooxygenase contributes to the maintenance of tension on stretching observed
      in tissues with epithelium.

PMID- 8307868
TI  - Influence of sleep on response to negative airway pressure of tensor palatini
      muscle and retropalatal airway.
AB  - Increased retropalatal airway resistance may be caused by a sleep-induced loss of
      palatal muscle activity and a diminished ability of these muscles to respond to
      the increasing intrapharyngeal negative pressure that develops during sleep. To
      investigate these possibilities, in six normal subjects, we determined the effect
      of non-rapid-eye-movement sleep on 1) the tensor palatini (TP) electromyogram
      (EMG) response to rapid-onset negative-pressure generations (NPG) in the upper
      airway and 2) the collapsibility of the retropalatal airway during these NPGs.
      During wakefulness, the change in TP EMG from basal to peak levels (during NPG)
      was 19.8 +/- 3.2 arbitrary units (P < 0.005). This was markedly reduced during
      sleep (3.6 +/- 1.5 arbitrary units; P < 0.001). The latency of the TP EMG
      response was 48.5 +/- 5.6 ms during wakefulness but was prolonged during sleep
      (105.0 +/- 12.2 ms; P < 0.02). The peak transpalatal pressure during NPG (a
      measure of airway collapse) was 2.1 +/- 0.7 cmH2O during wakefulness and
      increased to 5.3 +/- 0.8 cmH2O during sleep (P < 0.05). We conclude that the
      brisk reflex response of the TP muscle to negative pressure during wakefulness is
      markedly reduced during non-rapid-eye-movement sleep, in association with a more
      collapsible retropalatal airway. We speculate that the reduction in this TP
      reflex response contributes to retropalatal airway narrowing during sleep in
      normal subjects.

PMID- 8307869
TI  - Muscle metabolism during exercise in young and older untrained and endurance
      trained men.
AB  - To examine effects of aging and endurance training on human muscle metabolism
      during exercise, 31P magnetic resonance spectroscopy was used to study the
      metabolic response to exercise in young (21-33 yr) and older (58-68 yr) untrained
      and endurance-trained men (n = 6/group). Subjects performed graded plantar
      flexion exercise with the right leg, with metabolic responses measured using a
      31P surface coil placed over the lateral head of the gastrocnemius muscle. Muscle
      biopsy samples were also obtained for determination of citrate synthase activity.
      Rate of increase in P(i)-to-phosphocreatine ratio with increasing power output
      was greater (P < 0.01) in older untrained [0.058 +/- 0.022 (SD) W-1] and trained
      men (0.042 +/- 0.010 W-1) than in young untrained (0.038 +/- 0.017 W-1) and
      trained men (0.024 +/- 0.010 W-1). Plantar flexor muscle cross-sectional area and
      volume (determined using 1H magnetic resonance imaging) were 11-12% (P < 0.05)
      and 16-18% (P < 0.01) smaller, respectively, in older men. When corrected for
      this difference in muscle mass, age-related differences in metabolic response to
      exercise were reduced by approximately 50% but remained significant (P < 0.05).
      Citrate synthase activity was approximately 20% lower (P < 0.001) in older
      untrained and trained men than in corresponding young groups and was inversely
      related to P(i)-phosphocreatine slope (r = -0.63, P < 0.001). Age-related
      reductions in exercise capacity were associated with an altered muscle metabolic
      response to exercise, which appeared to be due to smaller muscle mass and lower
      muscle respiratory capacity of older subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307870
TI  - Gender differences in leucine kinetics and nitrogen balance in endurance
      athletes.
AB  - The current Canadian Recommended Nutrient Intake (RNI) for protein (0.86 g.kg
      1.day-1) makes no allowance for an effect of habitual physical activity. In
      addition, Tarnopolsky et al. (J. Appl. Physiol. 68: 302-308, 1990) showed that
      males may catabolize more protein than females consequent to endurance exercise.
      We examined nitrogen (N) balance and leucine kinetics during submaximal endurance
      exercise to determine the adequacy of the current Canadian RNI for protein for
      male and female endurance athletes. Athletes were matched for equal training
      volume, competitive status, and conditioning and were fed diets isoenergetic with
      their habitual intake, containing protein at the Canadian RNI. Subjects were
      adapted to the diet for 10 days before completing a 3-day measurement of N
      balance. N balance showed that the RNI was inadequate for females (-15.9 +/- 6.0
      mg.kg-1.day-1) and males (-26.3 +/- 11.0 mg.kg-1.day-1). Leucine kinetics during
      exercise were determined for each subject on day 3 of the N balance experiment by
      use of a primed continuous infusion of L-[1-13C]leucine and the reciprocal pool
      model. Exercise resulted in a significant (P < 0.01) increase in leucine
      oxidation for both groups. Males oxidized a greater amount of leucine during the
      infusion than females (P < 0.01). Leucine flux also increased significantly (P <
      0.01) during exercise in both groups. We conclude that the current Canadian RNI
      for protein is inadequate for those who chronically engage in endurance
      exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307871
TI  - Comparison of thoracoabdominal calibration methods in normal human subjects.
AB  - In 19 normal subjects in the supine posture, we compared accuracy and precision
      of calibration methods that utilized different ranges of tidal volumes and
      thoracoabdominal partitioning: spontaneous quiet breathing (QB), isovolume
      maneuvers, and voluntary efforts to breathe with variable tidal volume and
      thoracoabdominal partitioning. Thoracic and abdominal movements were measured
      with the respiratory area fluxometer. Calibration methods utilizing one or more
      types of respiratory efforts were applied to three measurement situations: QB,
      variable breathing (volume and thoracoabdominal partitioning), and simulated
      obstructive apnea (isovolume efforts). Qualitative diagnostic calibration (QDC)
      included QB data only. The isovolume method (ISOCAL) included isovolumetric
      efforts at end expiration (functional residual capacity) and QB. Multilinear
      regression analyses were performed on data sets that included 1) voluntary
      efforts to breathe with variable volume and thoracoabdominal partitioning (CAL
      1), 2) QB in addition to variable volume and partitioning (CAL 2), and 3)
      isovolume maneuvers in addition to QB and variable volume and partitioning
      efforts (CAL 3). When calibration data included a wide range of tidal volume,
      variable thoracoabdominal partitioning, and isovolume efforts (CAL 3), a stable
      calibration with small bias and scatter during all respiratory patterns was
      obtained. Excluding isovolume maneuvers (CAL 2) and QB (CAL 1) did not diminish
      accuracy. Limiting data to isovolume efforts at functional residual capacity plus
      QB (ISO-CAL) caused a significant increase in scatter during variable breathing
      patterns. Limiting calibration data to that portion of QB with small variation in
      the uncalibrated sum of thoracic and abdominal movements (QDC) caused significant
      increases in scatter in both isovolume efforts and variable breathing.

PMID- 8307872
TI  - Effects of eccentric exercise on insulin secretion and action in humans.
AB  - The effects of an exhaustive bout of eccentric exercise on insulin secretion and
      action were determined using the hyperglycemic clamp technique. Clamps were
      performed on eight healthy men after 7 days of inactivity and approximately 36 h
      after a bout of eccentric exercise. Eccentric exercise consisted of 10 sets of 10
      repetitions of combined knee extensions and flexions for each leg at a mean
      torque 84 +/- 5% of peak concentric torque. During the hyperglycemic clamp
      procedure, plasma glucose concentration was acutely raised to 10 mmol/l and was
      maintained near this level for 120 min. Arterialized blood samples were obtained
      from a heated hand vein to determine plasma glucose and insulin concentrations.
      Eccentric exercise appeared to produce marked muscle damage, as indicated by a 50
      fold increase in plasma creatine phosphokinase (100 +/- 17 vs. 5,209 +/- 3,811
      U/l, P < 0.001) and subjective reports of muscle soreness. Peak insulin response
      during the early phase (0-10 min) of the hyperglycemic clamp was higher after
      eccentric exercise (183 +/- 38 microU/ml) than after the control clamp (100 +/-
      23 microU/ml, P < 0.005). Late-phase (10- to 120-min) insulin response was not
      altered after eccentric exercise. Peak plasma C-peptide concentrations were
      higher during the early phase (5.0 +/- 0.7 vs. 4.3 +/- 0.8 ng/ml, P < 0.05) and
      the late phase (7.5 +/- 0.9 vs. 5.4 +/- 0.6 ng/ml, P < 0.05). Prior eccentric
      exercise had no significant effect on whole body glucose disposal or glucose
      disposal rate adjusted for prevailing plasma insulin concentration. These data
      provide evidence that a single bout of eccentric exercise causes an increase in
      pancreatic beta-cell insulin secretion in response to hyperglycemia.

PMID- 8307873
TI  - Asymmetric reflex responses of the nasal and tracheal vasculatures of the dog.
AB  - Both sides of the nasal vasculature of the dog in vivo were perfused separately,
      with measurement of vascular resistance responses to stimulation of various
      nerves. Stimulation of the central end of a cut superior laryngeal nerve caused
      an ipsilateral vasodilation (-4.98%) and a contralateral vasoconstriction
      (+3.96%), the difference being statistically significant (P < 0.01). Stimulation
      of a glossopharyngeal nerve caused vasodilation on both sides, the ipsilateral (
      17.52%) being greater than the contralateral (-6.33%) response (P < 0.05).
      Mechanical stimulation of the nasal mucosa caused little ipsilateral change
      (+0.47%) and a weak contralateral vasoconstriction (+3.78%; P < 0.01).
      Stimulation of the central end of a cervical vagus nerve caused vasodilations on
      both sides, the ipsilateral (-9.75%) being greater than the contralateral (
      5.73%) change (P < 0.05). With bilateral perfusions of the cervical tracheal
      arteries, stimulation of a superior laryngeal nerve caused vasodilation on both
      sides, the ipsilateral (-10.1%) being greater than the contralateral (-7.4%)
      response (P < 0.05). Stimulation of the central end of a vagus nerve caused
      vasoconstrictions on both the sides, the ipsilateral (+37.4%) being greater than
      the contralateral (+10.8%) change (P < 0.05). Thus various nervous inputs from
      the nose, pharynx, larynx, and vagal distribution cause asymmetric vascular
      responses both in the nose and in the cervical trachea.

PMID- 8307874
TI  - Effects of age and acclimation on responses to passive heat exposure.
AB  - To examine the effect of chronological age on thermoregulation during passive
      heat exposure, six older (O, 61 +/- 1 yr) and six young (Y, 26 +/- 2 yr) men sat
      at rest during a 30-min baseline period (dry-bulb temperature = 28 degrees C), a
      60-min thermal transient (28-46 degrees C by 2 degrees C steps every 5 min), and
      30 min at 46 degrees C dry-bulb temperature. Subjects were matched for maximal O2
      consumption, anthropometry, and body composition. Testing was repeated after a 9
      day active heat acclimation protocol. There were no age differences in rectal
      (Tre), mean skin (Tsk), or mean body temperature (Tb = 0.8Tre + 0.2Tsk) before or
      after acclimation, but heart rate was lower (P < 0.01) in the O group in both
      acclimation states. Heat acclimation resulted in a significantly lower baseline
      Tre and Tb in both groups, which remained lower throughout the passive heat
      stress (P < 0.05). To examine the effects of age and acclimation on
      thermoregulatory effector function, forearm blood flow (by venous occlusion
      plethysmography) and chest sweating rate (SRch, by dew-point hygrometry) were
      plotted against Tb. The slope of the forearm blood flow-Tb relationship was
      significantly (P < 0.05) lower in the O group before and after acclimation. A
      lower maximal SRch (P < 0.05) was achieved by the O group, but neither the slope
      of SRch-Tb relationship nor the Tb threshold for sweating was affected by age.
      Predictably, acclimation resulted in a lower Tb threshold for the onset of
      sweating and skin vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307875
TI  - Exogenous carbohydrate oxidation from different carbohydrate sources during
      exercise.
AB  - The exogenous carbohydrate (CHO) oxidation of naturally enriched [13C]CHO sources
      with different solubilities was studied during cycling exercise (150 min, 60%
      maximum work output). Moreover, the effect of adding a 13C tracer with different
      physical properties than the tracee on exogenous CHO oxidation was investigated.
      Test solutions (28.5 ml/kg body wt) were water for control of 13C background, 15%
      soluble partially hydrolyzed corn starch (SOL), 15% insoluble corn starch (In
      SOL), and 15% InSOL with [13C6]glucose as tracer. Both the mean and peak
      exogenous oxidation rates were significantly greater (P < 0.05) in the SOL trial
      than in the InSOL trial (mean oxidation rate, 0.84 +/- 0.21 and 0.50 +/- 0.15
      g/min, respectively; peak oxidation rate, 1.10 +/- 0.18 and 0.81 +/- 0.25 g/min,
      respectively). The amount of the ingested CHO that was oxidized was significantly
      higher (P < 0.05) in the SOL trial (126 +/- 31 g) than in the InSOL trial (75 +/-
      25 g). When we added an extrinsic tracer ([13C]glucose), the apparent mean and
      peak oxidation rates of the trial with InSOL and [13C6]glucose were significantly
      (P < 0.05) higher (0.91 +/- 0.30 and 1.23 +/- 0.41, respectively) than the InSOL
      values. These results 1) indicate that the addition of the soluble [13C]glucose
      tracer to an insoluble starch tracee leads to overestimation of the exogenous CHO
      oxidation rates and 2) suggest that soluble CHO is oxidized at a higher rate
      during exercise than isocaloric insoluble CHO.

PMID- 8307876
TI  - Reflex control of the tracheal vasculature of sheep.
AB  - Arteries to the cervical trachea were perfused at constant flow in anesthetized
      sheep. Perfusion pressures (PP), blood pressure (BP), and changes in tracheal
      smooth muscle tone (Ptr) were measured. Stimulation of pulmonary C-fiber
      receptors decreased PP (-6.5%) and BP (-16.8%) and increased Ptr (+61.5%),
      changes prevented by vagotomy and therefore reflex. Stimulation of cardiac
      receptors and slowly adapting pulmonary stretch receptors decreased PP (-7.9%)
      and BP (-21.0) and increased Ptr (+19.0%), changes reversed by vagotomy and
      therefore reflex. Stimulation and inhibition of slowly adapting pulmonary stretch
      receptors had no vagal-dependent effect on PP and BP, but inflation decreased (
      20.3%) and deflation increased Ptr (+35.2%), effects abolished by vagotomy and
      therefore reflex. Systemic hypoxia increased PP and BP before and after vagotomy
      (+12.2 and +40.3%), effects greatly reduced by cutting the carotid body nerves;
      it increased Ptr (+29.8%), an effect abolished by vagotomy and cutting the
      carotid body nerves. Systemic hypercapnia increased PP (+16.9%), BP (+20.5%), and
      Ptr (+36.2%), the first two responses being unaffected by vagotomy and the last
      almost abolished. Stimulation of carotid body chemoreceptors by KCN increased PP
      (+22.5%), BP (+104.7%), and Ptr (+8.5%), all responses prevented by cutting the
      carotid body nerves. Responses to intravenous injections of KCN were similar.

PMID- 8307877
TI  - Effect of ischemia-reperfusion on diaphragm strength and fatigability.
AB  - Although episodes of prolonged limb skeletal muscle ischemia followed by periods
      of reperfusion and reoxygenation are known to elicit free radical-mediated
      injury, the susceptibility of the diaphragm to this form of injury is not known.
      The purpose of the present study was to determine the effects of a period of
      severe partial ischemia, followed by reperfusion, on diaphragm contractile
      function. We also examined the effect of administration of a free radical
      scavenger, dimethyl sulfoxide (DMSO), on the diaphragmatic response to ischemia
      reperfusion. Experiments were performed on three groups of anesthetized dogs in
      which a vascularly isolated strip of diaphragm was dissected in situ: 1) a
      control group in which the diaphragm was perfused at the ambient systemic
      pressure, 2) a group in which the diaphragm was made ischemic for 3 h and
      reperfused for 1 h, and 3) a group given DMSO before periods of ischemia and
      reperfusion. In all groups, we measured diaphragm strip strength and
      fatigability; we also assessed diaphragm blood flow at several levels of
      contractile activity. Periods of ischemia, followed by reperfusion, were found to
      produce a downward shift of the diaphragm force-frequency relationship and also
      to markedly increase diaphragm fatigability. Diaphragm blood flow at rest and at
      low levels of contractile activity was unaffected by ischemia-reperfusion, but
      the flow achieved during fatiguing contractions was appreciably lower than that
      in nonischemic control animals. DMSO administration protected the diaphragm from
      the effects of ischemia-reperfusion, preventing alterations in fatigability and
      strength. Diaphragm flow in DMSO-treated animals was similar to that in
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307878
TI  - Metabolic basis for inspiratory muscle fatigue in normal humans.
AB  - Inspiratory muscle fatigue, a common event in patients in the intensive care
      unit, is under multifactorial control. To test the hypothesis that systemic
      oxygenation is a factor in this event, we subjected five healthy males (age 42 +/
      3 yr) to continuous inspiratory pressure (75% of maximal inspiratory pressure, 
      95 +/- 5 cmH2O) with the use of a controlled breathing pattern while they
      breathed normoxic (21% O2), hyperoxic (30% O2), and hypoxic (13% O2) mixtures.
      Inspiratory muscle endurance (IME; time that pressure could be maintained) and
      other cardiorespiratory parameters were monitored. Room air IME (3.3 +/- 0.4 min)
      was shortened (P < 0.05) during 13% O2 breathing (1.6 +/- 0.4 min) but was
      unaffected during 30% O2 breathing (4.0 +/- 0.6 min). Inspiratory loading lowered
      the respiratory exchange ratio (RER) during the 21 and 30% O2 trials (1.02 +/-
      0.01 to 0.80 +/- 0.03% and 1.05 +/- 0.05 to 0.69 +/- 0.01%, respectively) but not
      during the 13% O2 trials (1.03 +/- 0.03 to 1.06 +/- 0.07%). At the point of
      fatigue during the 13% O2 trials, RER was lower compared with the same time point
      during the 21 and 30% O2 trials. A significant relationship was observed between
      IME and RER (r = -0.73, P = 0.002) but not between IME and any of the other
      measured variables. We conclude that 1) hypoxemia impairs the ability of the
      inspiratory muscles to sustain a mechanical challenge and 2) substrate
      utilization of the respiratory muscles shifts toward a greater reliance on lipid
      metabolism when O2 is readily available; this shift was not observed when the O2
      supply was reduced.

PMID- 8307879
TI  - Reflex bronchial vasodilation in dogs evoked by injection of a small volume of
      water into a bronchus.
AB  - Injection of water into a lobar bronchus stimulates airway C-fibers and rapidly
      adapting receptors and evokes airway defense reflexes. To determine whether this
      stimulus also evokes a reflex increase in bronchial blood flow (Qbr), we injected
      1-2 ml of water into a lobar bronchus in anesthetized dogs. Injection decreased
      arterial pressure but increased Qbr from 9 +/- 1 to 21 +/- 3 ml/min. The increase
      had a latency of 6-8 s and reached a peak after approximately 20 s; Qbr returned
      to control after 60-90 s. Airway mucosal blood flow, measured by colored
      microspheres, increased in proportion to Qbr. In contrast, flow in an adjacent
      intercostal artery that did not supply the airway decreased slightly. Injection
      of isosmotic saline had little effect. In 13 of 16 dogs, the water-induced
      increase in Qbr was abolished by cutting or cooling the cervical vagus nerves and
      hence was entirely dependent on centrally mediated vagal pathways. When the vagus
      nerves were intact, about one-third of the vasodilator response remained after
      pharmacological blockade of muscarinic and adrenergic receptors. We conclude that
      in dogs the defense response to water in the lower airways includes a large
      increase in Qbr that is partly due to activation of nonadrenergic noncholinergic
      autonomic pathways.

PMID- 8307880
TI  - Histomorphometric analyses of cancellous bone from COSMOS 2044 rats.
AB  - The influence of 14 days of spaceflight on cancellous bone of male Wistar rats
      was assessed by histomorphometric analysis. In proximal tibia, no difference was
      found between flight, synchronous, vivarium, and basal groups for epiphyseal bone
      volume or trabecular arrangement. In metaphysis, primary spongiosa width was
      reduced in flight rats, suggesting an alteration in bone longitudinal growth. In
      flight rats, secondary spongiosa evidenced a trend toward decreased bone mass,
      trabecular number and thickness, and osteoid surfaces, whereas there was a
      tendency toward increased osteoclast number compared with vivarium control but
      not with synchronous rats. In femoral fossa trochanteri, an area facing deep
      muscular insertions, no changes in bone volume or structure were noted among the
      different groups. However, a reduction of osteoid surfaces was seen in flight and
      synchronous groups compared with the other groups. Resorption activity was
      increased in flight rats compared with control rats. In thoracic vertebral body,
      osteoblastic surfaces decreased similarly in flight and synchronous rats. In
      lumbar vertebral body, decreased osteoblastic surfaces and increased osteoclastic
      parameters were observed in flight and synchronous rats. The more striking
      effects of spaceflight were the decrease in tibial primary spongiosa width and
      the increase in resorption activity of the femoral fossa trochanteri. In all
      other sites, cellular alterations appeared similar in flight and synchronous
      rats, suggesting a role for physiological stress. The time course of events would
      depend on initial growth and turnover rates of bone, its weight-bearing function
      on earth, and the presence of muscular insertions.

PMID- 8307881
TI  - Ventilatory sensitivity to CO2 in hyperoxia and hypoxia in older aged humans.
AB  - Findings from studies of the effects of aging on the human respiratory controller
      are equivocal. This study assessed the ventilatory response to CO2 in hyperoxia
      and hypoxia in groups of younger (YS) and older (OS) humans. Two protocols were
      used. In the first, end-tidal PCO2 (PETCO2) was clamped at 1-2 Torr above rest
      (eucapnia), and, in the second, PETCO2 was clamped at 7-8 torr above resting
      PETCO2 (moderate hypercapnia). End-tidal PO2 was clamped at 100 Torr throughout
      except for two 2-min periods at 500 and 50 Torr. The ventilatory responses for
      each subject at each PO2 were fitted to the linear equation, VE = S(PETCO2 - B),
      where VE is minute ventilation, S is the response curve slope, and B is the
      response curve threshold. In eucapnia, there were no differences in hypoxic and
      hyperoxic VE between YS and OS. In hypercapnia, hypoxic VE was 24% lower in OS
      [39.93 +/- 2.71 (SE) l/min] than in YS (52.16 +/- 3.17 l/min). In hypoxia, S was
      significantly lower in OS (3.25 +/- 0.38 l.min-1.Torr-1) than in YS (4.76 +/-
      0.37 l.min-1.Torr-1). We conclude that, in older humans, VE is lower in hypoxia
      during moderate hypercapnia, resulting mainly from a decreased peripheral
      chemoreflex CO2 sensitivity.

PMID- 8307882
TI  - Modulation of the QT interval: effects of graded exercise and reflex
      cardiovascular stimulation.
AB  - During exercise, as heart rate (HR) increases, the QT interval of the
      electrocardiogram shortens. The mechanism(s) involved in this QT shortening has
      not been clearly defined. To distinguish the influence of increased circulating
      catecholamines from myocardial efferent stimulation, the relationship between HR
      and QT interval was investigated during exercise and cardiovascular reflex
      stimulation in cardiac transplant patients and normal control subjects. Because
      of cardiac denervation, increases in HR in these patients are solely due to
      circulating catecholamines and thus allow isolation of their effect on the QT
      interval. Twenty-one cardiac transplant patients were studied and compared with
      16 normal control subjects. The QT-HR relationship was determined according to an
      exponential model during treadmill exercise in both groups [QT = 0.12 + 0.492e(
      0.008.HR) and QT = 0.12 + 0.459e(-0.007.HR) in normal subjects and transplant
      patients, respectively] and was statistically similar between groups, suggesting
      similar QT interval shortening in both groups. During cold pressor and Valsalva
      maneuvers, HR increased significantly in normal subjects only, whereas QT
      interval changed minimally in both groups. These results suggest that during
      exercise the QT interval is influenced predominantly by increases in circulating
      catecholamines rather than by neurally mediated reflex autonomic changes.

PMID- 8307883
TI  - Influence of body position on diaphragmatic and scalene activation during hypoxic
      rebreathing.
AB  - We measured electromyographic activity of the diaphragm (EMGdi) and scalene
      (EMGsc) during isocapnic progressive hypoxic ventilatory responses in five normal
      males in the supine and upright seated positions. The slope of the regression
      line relating EMGdi expressed as a percentage of maximum to percent fall in
      arterial oxyhemoglobin saturation was 93% steeper upright than supine (P <
      0.005), whereas the slope of EMGdi activity to minute volume of ventilation was
      73% higher upright than supine (P < 0.05). In addition, the slope of EMGsc
      activity relative to percent fall in arterial oxyhemoglobin saturation and minute
      ventilation was greater upright than supine (151%, P < 0.001 and 61%, P = 0.056,
      respectively). Greater EMGsc activity upright than supine was similar to findings
      during hypercapnic rebreathing. However, the greater EMGdi activity upright than
      supine stands in contrast to hypercapnic rebreathing where it was previously
      shown that EMGdi activity was not affected by a change in body position. We
      conclude that during hypoxic ventilatory responses both EMGdi and EMGsc
      activities are more pronounced upright than supine. Diaphragmatic activation
      during progressive hypoxia in response to a change in body position is different
      from that seen during progressive hypercapnia.

PMID- 8307884
TI  - Assessment of methacholine-induced airway constriction by ultrafast high
      resolution computed tomography.
AB  - Assessment of changes in airway dimensions during bronchoconstriction is
      conventionally based on measurements of respiratory mechanics. We evaluated the
      efficacy of ultrafast high-resolution computed tomography (UHRCT) to directly
      determine the dynamic changes in cross-sectional area (CSA) of airways in
      response to methacholine (MCh). UHRCT scans were obtained at functional residual
      capacity before (baseline) and after intravenous bolus injections of MCh (10(
      8.5)-10(-7.0) mol/kg) to seven mechanically ventilated pigs. Changes in CSA of
      bronchi of varying baseline size (1-10 mm diam) were determined by using a
      customized image processing software package (VIDA) based on a user-directed
      computer-adjusted edge-finding algorithm. MCh induced dose-dependent decreases in
      CSA, which were paralleled by increases in airway opening pressure at higher
      doses of MCh; at lower doses of MCh, decreases in CSA of smaller airways were
      detected without concomitant changes in airway opening pressure. Changes in CSA
      were heterogeneous and variable, especially in the smaller airway ranges. The
      results of the present study support the concept that UHRCT can be used in
      conjunction with bolus challenges to effectively determine dose-response changes
      in airway caliber in both large and small airways. This technique provides data
      that may not be reflected by conventional lung function measurements and, hence,
      is a useful tool to study airway reactivity.

PMID- 8307885
TI  - Generation and transit pathway of H+ is critical for inhibition of palmar
      sweating by iontophoresis in water.
AB  - Passing galvanic current across the skin (known as "tap water iontophoresis" or
      TWI) inhibits sweating; however, its mechanism of action is unclear. Using
      improved methods, we confirmed that anodal current has more of an inhibitory
      effect than cathodal current, water is superior to saline, and the inhibitory
      effect is a function of the amperage used. To address the importance of current
      flowing through the pores, a layer of silicone grease was placed on the skin to
      reduce the shunt pathway across the epidermis. With silicone, total skin
      conductance decreased 60% without the sweat pores being occluded, swelling of the
      stratum corneum and collapse of the poral lumen was prevented, and current
      induced inhibition of sweating was enhanced, most likely because of an increase
      in current density in the pores. The pH of anodal water, but not of saline,
      dropped to 3, whereas that of cathodal water increased to 10 during passage of
      current through the skin. Acidified anodal water was superior to alkaline water.
      Sweat glands isolated from TWI-induced anhidrotic palmar skin responded to
      methacholine in vitro, but the sweat rate and pharmacological sensitivity were
      slightly lowered. Thus the strong acidity generated by hydrolysis of water in the
      anodal bath and the further accumulation of H+ in the sweat duct by anodal
      current may be responsible for TWI-induced inhibition of sweating due to an
      unknown lesion(s) in the duct or sweat pore. The secretory coil function may also
      be altered because of exposure to intense acidity during TWI. The importance of
      H+ movement into the sweat pore for inhibition of sweating could be further
      exploited to develop new strategies for the control of sweating.

PMID- 8307886
TI  - Mechanical determinants of isotonic relaxation in isolated diaphragm muscle.
AB  - Determinants of lengthening velocity have not been investigated in the diaphragm
      muscle. This study was undertaken to define the mechanical determinants of
      isotonic relaxation rate over the entire load continuum in isolated rat diaphragm
      (n = 30). We tested the hypothesis that the determinants of lengthening could
      include loading conditions, namely, preload and afterload; abrupt changes of load
      during the contraction phase; end-shortening muscle length (ESL); extent of
      shortening (delta L); time; stimulation mode; and stimulation frequency. In
      afterloaded contractions preloaded at optimal initial length and stimulated in
      tetanus at 30 Hz, peak lengthening velocity (+dL/dtmax) was linearly related to
      delta L, ESL, and/or total load. Varying initial muscle length, ESL, afterload,
      or the load imposed on the muscle during the isotonic lengthening process did not
      modify +dL/dtmax vs. delta L relationship, whereas +dL/dtmax vs. load and
      +dL/dtmax vs. ESL relationships were modified by these procedures. For a given
      delta L, +dL/dtmax could be modified when lengthening was delayed by reversing
      the relaxation sequence and when twitch and tetanus modes were compared. In
      conclusion, our results demonstrate that in isolated diaphragm muscle, delta L is
      the main determinant of +dL/dtmax over a wide range of loads and under various
      experimental conditions, independent of ESL and initial muscle length and
      independent of the load imposed on the muscle during the lengthening process.
      Time and stimulation mode were also shown to modulate the lengthening rate in
      diaphragm muscle.

PMID- 8307887
TI  - Velocity profiles measured for airflow through a large-scale model of the human
      nasal cavity.
AB  - An anatomically accurate, x20 enlarged scale model of a healthy right human adult
      nasal cavity was constructed from computerized axial tomography scans for the
      study of nasal airflow patterns. Detailed velocity profiles for inspiratory and
      expiratory flow through the model and turbulence intensity were measured with a
      hot-film anemometer probe with 1 mm spatial resolution. Steady flow rates
      equivalent to 1,100, 560, and 180 ml/s through one side of the real human nose
      were studied. Airflows were determined to be moderately turbulent, but changes in
      the velocity profiles between the highest and lowest flow rates suggest that for
      normal breathing laminar flow may be present in much of the nasal cavity. The
      velocity measurements closest to the model wall were estimated to be inside the
      laminar sublayer, such that the slopes of the velocity profiles are reasonably
      good estimates of the velocity gradients at the walls. The overall longitudinal
      pressure drop inside the nasal cavity for the three inspiratory flow rates was
      estimated from the average total shear stress measured at the central nasal wall
      and showed good agreement with literature values measured in human subjects.

PMID- 8307888
TI  - Density of decompression bubbles and competition for gas among bubbles, tissue,
      and blood.
AB  - We used numerical solutions of a system of equations to simulate gas exchanges of
      bubbles after a decompression, with particular attention to the effect of number
      of bubble formation sites per unit of tissue. If many bubbles grow, they deplete
      the excess dissolved gas in the tissue. The consequences are as follows: 1) the
      many individual bubbles do not become as large as they would if fewer were
      competing for gas; 2) more gas is evolved when there are many sites; 3) the
      bubbles are absorbed sooner than the bigger bubbles that grow with few sites; 4)
      after diffusion into many bubbles causes N2 partial pressure in the tissue to
      fall immediately to a low level, N2 partial pressure in the tissue and the
      exiting blood remain "clamped" to this low level because dissolved N2 removed by
      blood is replenished by diffusion out of the bubbles; and 5) as long as many
      bubbles persist, the long-term removal of inert gas from the total system (tissue
      plus bubbles) follows a straight-line time course rather than an exponential
      course.

PMID- 8307889
TI  - CO2 homeostasis during periodic breathing: predictions from a computer model.
AB  - The Bohr/Riley model of CO2 homeostasis describes the relationship between CO2
      production, ventilation, and arterial PCO2 and assumes that ventilation and CO2
      delivery to the lung are both anatomically and temporally well matched. In
      contrast to normal breathing, periodic patterns of ventilation show temporal
      mismatch of ventilation to CO2 delivery. We developed a computer model of lung
      CO2 clearance that uses CO2 transfer equations to generate iterative solutions
      for PCO2 in multiple body compartments as a function of time. During continuous
      ventilatory patterns our model predicts steady-state arterial PCO2 identical to
      that of the Bohr model. During periodic ventilation, we predict mean PCO2 will be
      elevated unless mean ventilation is increased above that required by the Bohr
      model. Waxing and waning tidal volumes, low functional residual capacity, and low
      capillary blood volume potentiate the hypercapnia. However, if cardiac output
      oscillates in phase with breathing, hypercapnia is minimized. This analysis
      suggests a new mechanism for the development of sustained hypercapnia, separate
      from absolute hypoventilation or the presence of lung disease.

PMID- 8307890
TI  - Important influence of respiration on human R-R interval power spectra is largely
      ignored.
AB  - Frequency-domain analyses of R-R intervals are used widely to estimate levels of
      autonomic neural traffic to the human heart. Because respiration modulates
      autonomic activity, we determined for nine healthy subjects the influence of
      breathing frequency and tidal volume on R-R interval power spectra (fast-Fourier
      transform method). We also surveyed published literature to determine current
      practices in this burgeoning field of scientific inquiry. Supine subjects
      breathed at rates of 6, 7.5, 10, 15, 17.1, 20, and 24 breaths/min and with
      nominal tidal volumes of 1,000 and 1,500 ml. R-R interval power at respiratory
      and low (0.06-0.14 Hz) frequencies declined significantly as breathing frequency
      increased. R-R interval power at respiratory frequencies was significantly
      greater at a tidal volume of 1,500 than 1,000 ml. Neither breathing frequency nor
      tidal volume influenced average R-R intervals significantly. Our review of
      studies reporting human R-R interval power spectra showed that 51% of the studies
      controlled respiratory rate, 11% controlled tidal volume, and 11% controlled both
      respiratory rate and tidal volume. The major implications of our analyses are
      that breathing parameters strongly influence low-frequency as well as respiratory
      frequency R-R interval power spectra and that this influence is largely ignored
      in published research.

PMID- 8307891
TI  - Intravasal use of pliable K(+)-selective electrodes in the femoral vein of humans
      during exercise.
AB  - Continuous recording of plasma K+ concentration ([K+]) during exercise would be
      valuable in determining K+ fluxes associated with muscle activation. Pliable
      polyvinyl chloride electrodes were constructed by incorporation of valinomycin
      into a polyvinyl chloride membrane attached to the end of a catheter with a 1 mm
      outer diameter. Through an outer catheter the electrode was inserted into the
      femoral vein of human subjects. The setup allowed easy in vivo calibration, and
      rapid changes of femoral venous [K+] of < 0.1 mmol/l could easily be detected.
      Drift over 1 h amounted to < 3 mV and was corrected for by analysis of blood
      samples. Rapid changes in femoral venous [K+] occurred during and after dynamic
      exercise, short and prolonged isometric contractions, and repetitive isometric
      contractions of the quadriceps muscle. Combined with arterial blood sampling and
      flow measurements, the electrodes will allow good approximation of 1) cellular K+
      efflux rate associated with increased electrical activity, 2) rate of
      intramuscular reuptake of K+ mediated by the Na(+)-K+ pump, and 3) rate of K+
      loss to or uptake from the circulation by the muscle.

PMID- 8307892
TI  - Effect of common vasodilators on lung microvascular permeability.
AB  - The effect of papaverine on the albumin permeability-surface area product (PS),
      reflection coefficient (sigma), and capillary filtration coefficient (Kf) was
      examined in isolated rabbit lungs. Because PS and Kf are functions of vascular
      surface area and permeability, we also compared papaverine with two other means
      of maximizing lung surface area: isoproterenol (1 x 10(-7) M) and a mild increase
      in vascular pressure. Only lungs perfused with 0.1 mg/ml papaverine were
      significantly different from control. PS increased from control (2.80 +/- 0.16 to
      5.53 +/- 0.20 ml.min-1.g dry lung-1 x 10(-2), whereas sigma decreased from
      control (0.92 +/- 0.01 to 0.78 +/- 0.03). Kf after papaverine was significantly
      lower than baseline predrug Kf (5.60 +/- 0.78 to 4.56 +/- 0.53 ml.s-1.cmH2O-1.g
      dry lung-1 x 10(-3). However, this group's predrug Kf was higher than that of any
      other group. Our results indicate that papaverine increases albumin permeability
      and decreases endothelial selectivity. The isolated perfused lung appears fully
      recruited, because Kf and PS did not increase with isoproterenol or increased
      vascular pressure. Papaverine should be used with caution in the Ringer-perfused
      lung.

PMID- 8307893
TI  - Nitric oxide inhibition varies with hemoglobin saturation.
AB  - Endothelium-derived nitric oxide (NO) appears to be involved in the regulation of
      pulmonary vascular tone by O2. We hypothesized that the ability of blood to
      inhibit the vasodilation caused by NO would vary inversely with the saturation of
      hemoglobin by O2. To test this hypothesis, we used the pulmonary circulation of
      the unanesthetized fetal lamb as a bioassay for NO-induced vasodilation. Two to 3
      days before the experiment, the main pulmonary artery, left atrium, carotid
      artery, and trachea of the fetus were catheterized and an ultrasonic blood flow
      transducer was placed around the proximal portion of the left pulmonary artery.
      On the day of the experiment, NO solution was prepared by bubbling 10% NO-90% N2
      gas mixture in saline. This solution was injected into the fluid-filled potential
      air spaces of the fetal lungs via the trachea. At the highest dose (0.8 mumol),
      NO increased pulmonary blood flow fourfold and decreased pulmonary vascular
      resistance similarly. The dose-response curve for NO was similar to those
      obtained from isolated pulmonary blood vessels and gas-ventilated animals. Mixing
      NO solution with maternal arterial blood before injection decreased the effect of
      NO, and mixing it with venous blood virtually eliminated the effect. The decrease
      in fetal pulmonary vascular resistance caused by NO was inhibited by blood in
      inverse proportion to the saturation of hemoglobin with O2 in the blood (R2 =
      0.93, P < or = 0.0001), confirming our hypothesis.

PMID- 8307894
TI  - Electrophoretic separation of rat skeletal muscle myosin heavy-chain isoforms.
AB  - A new technique for the sodium dodecyl sulfate-polyacrylamide gel electrophoretic
      separation of rat skeletal muscle myosin heavy-chain (MHC) isoforms is presented.
      This technique allows for the separation of the four identified MHC isoforms
      known to be present in adult rat skeletal muscle. These types of MHC are commonly
      called I, IIa, IIx or IId, and IIb. The procedure can be performed using minigel
      electrophoresis systems and does not involve preparation of gradient-separating
      gels or the use of special cooling devices. The procedure accommodates both
      silver and Coomasie Blue staining. Thus the procedure is simple to perform and
      highly repeatable, providing high-resolution separation of MHC protein isoforms.
      The percent composition of the four adult MHCs in rat soleus, medial
      gastrocnemius, diaphragm, and levator ani muscles by use of this procedure and
      Coomasie Blue staining is similar to that previously reported. This new technique
      provides a novel and easy-to-perform method for the separation of rat skeletal
      muscle MHC isoforms.

PMID- 8307895
TI  - Underestimation of substrate oxidation during exercise due to failure to account
      for bicarbonate kinetics.

PMID- 8307896
TI  - Effects of diabetes on cardiac glycogen metabolism in rats.
AB  - The effects of diabetes on myocardial glycogen metabolism in rats were examined
      and compared with those of fasting. Male Wistar rats were divided into three
      groups: controls, streptozotocin-induced diabetics, and one-week fasted. Isolated
      rat hearts were subjected to substrate-free 30-min Langendorff perfusion followed
      by 60-min working heart perfusion with glucose alone or in combination with
      insulin or insulin plus beta-hydroxybutyrate (BHB). Myocardial glycogen contents
      were determined before or 30 min after Langendorff perfusion, or 60 min after
      working heart perfusion. Before Langendorff perfusion, tissue glycogen
      concentrations in control, diabetic, and fasted hearts were 3.3 +/- 0.2, 10.0 +/-
      0.9, and 5.7 +/- 0.5 (mg/g wet weight), respectively. In diabetic rats, the
      myocardial glycogen concentration was markedly decreased after working heart
      perfusion of any of the substrate combinations, even those with insulin and BHB.
      In contrast, myocardial glycogen in control or fasted rats was not reduced after
      the addition of glucose with insulin, and/or glucose with insulin and BHB. These
      results suggest that degradation of tissue glycogen occurs in isolated perfused
      hearts from diabetic rats, while a clearly different response is shown by fasted
      hearts.

PMID- 8307897
TI  - Smooth muscle responses of the rat septal artery are not influenced by
      surrounding passive cardiac tissue.
AB  - We investigated the possible contribution of surrounding passive cardiac tissue
      to the smooth muscle responses of coronary arteries. The vasoactive properties of
      the intramyocardial septal artery (outer diameter 350-400 microns) of the rat
      heart were investigated when it was freed from the surrounding cardiac tissue
      (dissected artery) and when it remained in the left ventricle and was thus
      embedded in passive cardiac tissue (in situ). The changes in external diameter
      relative to the maximal diameter (isoproterenol) resulting from the application
      of 125 mM KCl and 1,000 microU/ml vasopressin were measured at 37 degrees C, a
      transmural pressure of 100 cm H2O, and zero flow. In the dissected septal
      arteries (n = 5) the maximum diameter was 402 +/- 16 microns, while during
      exposure to KCl and vasopressin the diameter was reduced to 66.1 +/- 4.6% and
      74.2 +/- 3.0%, respectively. For the in situ arteries (n = 6), the maximal
      diameter was 386 +/- 28 microns, a value not statistically different from the
      dissected vessels and the diameters reduced to 63.2 +/- 5.5% and 65.6 +/- 7.2%
      due to KCl and vasopressin, respectively. The constrictions of dissected arteries
      and in situ arteries were statistically not different. The results show that the
      maximally-dilated diameter and the constriction responses of intramyocardial
      conduit arteries of the rat heart are not affected by the surrounding passive
      cardiac tissue.

PMID- 8307898
TI  - Three-dimensional distribution of myocardial fibrosis in the new J-2-N
      cardiomyopathic hamster: comparison with electrocardiographic findings.
AB  - Using the new J-2-N strain of cardiomyopathic hamster obtained by cross-breeding
      Bio 14.6 and Golden hamsters, we investigated the three-dimensional distribution
      of ventricular myocardial fibrosis and compared it with electrocardiographic
      (ECG) changes. Twelve-lead ECG recordings were made by our own method. The hearts
      were cut into serial sections and subjected to light microscopic examination. The
      distribution, density, and volume of myocardial interstitial fibrosis and
      replacement fibrosis due to myocardial degeneration (F%) were visualized three
      dimensionally using the TRI system (TRI; Three-Dimensional Reconstruction Image;
      Ratoc System Engineering, Tokyo, Japan). Thirty-two J-2-N hamsters were divided
      into two groups; one group comprised 17 animals with normal hearts and normal ECG
      findings similar to those of Golden hamsters, and the other group of 15 hamsters
      had dilated hearts and abnormal ECG findings. In the normal hearts, the F% values
      for the right ventricle, left ventricle, and ventricular septum were 6.4 +/-
      0.94, 6.5 +/- 0.95, and 6.5 +/- 0.98 (mean +/- SD), respectively. The dilated
      hearts showed marked fibrosis, which was distributed mainly in the middle layer
      of the left ventricle and the ventricular septum. The corresponding F% values for
      the hamsters with cardiac enlargement were 19 +/- 2.6, 19 +/- 1.8, and 22 +/- 3.2
      (mean +/- SD), respectively. Replacement of myocytes by fibrosis seemed to
      correspond to abnormal Q waves in the anterior chest leads and left axis
      deviation of the QRS complex.

PMID- 8307899
TI  - Velocity profiles in the ascending aorta in pigs: axial development and influence
      of changes in left ventricular contraction pattern.
AB  - Earlier studies using hot-film anemometry in pigs have revealed skewed
      tangentially rotating velocity profiles in the ascending aorta during systole.
      The reason for this phenomenon has been postulated to be caused by the left
      ventricular contraction pattern. Therefore, the aim of this study was to
      investigate the influence of the left ventricular contraction pattern on the
      velocity fields in the ascending aorta of pigs. We used a 10 MHz perivascular
      pulsed Doppler ultrasound system to measure point blood velocities at two axial
      locations over the entire cross sectional area in the ascending aorta of 90 kg
      pigs. The axial component of the velocity profiles was visualized dynamically by
      computerized 3-dimensional animation techniques. Changing left ventricular
      contraction patterns were accomplished by reversible occlusion of either the left
      anterior descending or right posterior descending coronary artery. The axial
      development of the systolic rotating and skewed velocity profiles in the
      ascending aorta was described. The appearance of the systolic velocity profiles
      were virtually unaffected by changes in left ventricular contraction pattern.

PMID- 8307900
TI  - Pharmacological intervention for renal protection during cardiopulmonary bypass.
AB  - The possibility of minimizing organ damage following cardiopulmonary bypass (CPB)
      was examined. In the control group, n = 21, upon completion of CPB, elevation of
      the lysosomal enzyme beta-glucuronidase, which is a sensitive indicator of
      cellular damage, was affected by the concentration of granulocyte elastase (r =
      0.59) or the endothelial-derived constricting factor, endothelin, (r = 0.8).
      Renal damage, which was detected by an increase in renal tubular enzymes (N
      acetyl-beta-D-glucosaminidase and gamma-glutamyltranspeptidase) in urine, was
      also affected by endothelin (r = 0.79, r = 0.56), elastase (r = 0.6, r = 0.71),
      and by free hemoglobin levels (r = 0.76, r = 0.82). Next, the efficacy of
      pharmacological intervention for the prevention of renal damage was evaluated.
      During CPB, the administration of an elastase inhibitor (ulinastatin, 3 x 10(5)
      IU), n = 8, or a calcium antagonist (nicaldipine HCl, elastase release inhibitor;
      5 gamma/kg per min), n = 8, significantly reduced the elevation of beta
      glucuronidase and renal tubular enzymes (p < 0.05). Although the ulinastatin and
      nicardipine groups demonstrated low values of elastase in the Intensive Care Unit
      (ICU), only the values of the nicardipine group reached statistical significance
      (p < 0.05). A reduction in endothelin levels compared to the control group was
      observed in the nicardipine group. However, preventive and counteractive effects
      of nicardipine against vasoconstriction caused by endothelin were also considered
      to play an important role in the prevention of renal damage. The addition of
      haptoglobin (4,000 IU) to the priming solution of the CPB also reduced levels of
      renal tubular enzymes (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8307901
TI  - Hemangioma of the left ventricular cavity: presumptive diagnosis by magnetic
      resonance imaging.
AB  - In a 16-year-old boy, magnetic resonance imaging (MRI) revealed a 1 x 1.5-cm
      tumor on a stalk attached to the anterior ventricular wall. The tumor showed
      homogeneous enhancement after the administration of gadolinium(Gd)-DTPA,
      indicating it was highly vascular. The tumor was excised during surgery and the
      histological examination led to a diagnosis of juvenile hemangioendothelioma. MRI
      therefore allowed a definitive diagnosis of cardiac hemangioma to be made
      preoperatively. This case represents the first reported instance of a benign left
      ventricular hemangioma diagnosed by MRI.

PMID- 8307902
TI  - A message from your president. AMS announces managed care initiative.

PMID- 8307903
TI  - Managed care feasibility study for the Arkansas Medical Society.

PMID- 8307904
TI  - Utilization review puts doctors on a tightrope.

PMID- 8307905
TI  - Radiological case of the month. Ganglion cyst with suprascapular nerve
      entrapment.

PMID- 8307906
TI  - Tight diabetes control: can it prevent complications?

PMID- 8307907
TI  - The how and what of CNS tuberculomas.

PMID- 8307908
TI  - A retrospective study of 1247 cases of intracranial tuberculomata diagnosed by
      computerized tomography.
AB  - Tuberculomata in the brain are a common feature of intracranial tuberculosis,
      especially in the sub-continent. With the advent of computerized tomography, a
      diagnosis can be made, in many instances. In this study, 1247 cases of CT
      diagnosed intracranial tuberculomata were analysed retrospectively with regard to
      the age, sex and symptoms of the patient as well as the number, site and
      distribution of the lesion within the brain. Tabulation with respect to age
      revealed that patients with ages ranging from 1-30 years accounted for 60% of the
      cases. The male to female ratio was approximately 60:40. The parietal hemisphere
      accounted for 46.75% of the cases. Left sided lesion were more common when
      compared with the right (statistically significant). We postulate that this
      increased occurrence of left sided lesions is due to the hematogenous mode of
      infection and increased blood flow to the dominant hemisphere.

PMID- 8307909
TI  - Prevalence of microalbuminuria in diabetic subjects.
AB  - Total 193 diabetic patients were investigated to assess the prevalence of
      microalbuminuria. Urinary albumin excretion rate (UAER) was measured by
      radioimmunoassay (RIA) on 3 hours urine samples. The prevalence of
      microalbuminuria (UAER) > 15 micrograms/min was 41%. Microalbuminuria was
      commonly observed in patients having diabetes for more than 5 years. A
      significant correlation was found between duration of diabetes and
      microalbuminuria (p < 0.01). Glycemic control (fasting and postprandial blood
      sugar) did not show any correlation with UAER, whereas blood urea (r.39, p <
      0.01), creatinine (r.26, p < 0.05) and chloride (r.24, p < 0.05) were positively
      correlated. A significant correlation was found between raised blood pressure and
      UAER (p < 0.01).

PMID- 8307910
TI  - Autonomic and peripheral neuropathy in insulin dependent diabetics.
AB  - Twenty five diabetics (all insulin dependent) and 20 age and sex matched controls
      were studied to assess peripheral nerve functions and autonomic (cardiovascular
      and urinary bladder) nerve functions. Impotence was the commonest symptom
      followed by postural dizziness, atonic bladder, shooting pains in the limbs and
      gustatory sweating. Cardiac autonomic neuropathy was found in 60% of the
      diabetics while 68% of them had diabetic cystopathy. Peripheral nerve dysfunction
      was present in 80% of the patients. Forty percent of the diabetics had all the
      three forms of neuropathies (cardiac, urinary bladder and peripheral), while
      another 40% of the patients had at least two forms of neuropathy.

PMID- 8307911
TI  - Detection of autonomic nervous dysfunction by SL manoeuvre.
AB  - We have evaluated the immediate heart rate response to standing and lying and in
      100 Diabetic subjects aged 43 +/- 10 years who underwent five other
      cardiovascular autonomic tests. Using a specially devised scoring system the
      patients were divided into three groups: a) 58 subjects without autonomic
      neuropathy, b) 15 borderliners, c) 27 with autonomic neuropathy. The results were
      compared with 50, sex and age matched controls. We studied SL1 = ratio between R
      R mean before lying and R-R maximum between the 20th to 25th beat and R-R minimum
      over the first 5 beats after lying. In controls SL1 was 1.35 +/- 0.18 and SL2 was
      1.52 +/- 0.23. In diabetic subjects without autonomic neuropathy SL1 was 1.20 +/-
      0.86 (p < 0.01), SL2 1.50 +/- 0.02 (p < 0.001). In the group with autonomic
      neuropathy SL1 was 1.04 +/- 0.02 (p < 0.001) and SL2 was 1.20 +/- 0.09 (p <
      0.001). We propose that the lowest normal and highest abnormal limits of SL1 are
      1.12 and 1.08 respectively and that normal and highest abnormal limits of SL2 are
      1.23 and 1.18 respectively. We suggest the use of SL1 as a pure parasympathetic
      test and SL2 as a mixed but predominantly sympathetic test in the diagnosis of
      autonomic neuropathy.

PMID- 8307912
TI  - Toxicity of exposed aluminium phosphide.
AB  - Poisoning by the partially or fully exposed compound of aluminium phosphide (ALP)
      is becoming common, Fifty patients with history of ingestion of ALP either in the
      form of broken tablets or granular powder were included in this study for
      analysis of systemic effects and outcome. Forty patients (Gr. I) consumed broken
      or granular form of tablets. Ten patients (Gr. II) consumed only powder form of
      tablets from an old container. 30 patients in group-I developed mild hypotension
      (BP 80-90 mm Hg). 4 patients (10%) developed ECG changes and mild metabolic
      acidosis. One patient died constituting 2.5% mortality rate. The patients of
      group-II neither developed any systemic effects nor showed any mortality. The aim
      of the study is to differentiate these cases from patients who consume active,
      fresh compound where mortality rate will be much higher.

PMID- 8307913
TI  - Patterns of rheumatic diseases and antirheumatic drug usage in 11931 Indian
      patients.
AB  - Patterns of rheumatic diseases and antirheumatic drug usage in different regions
      of India were analysed. The data was collected from a post-marketing surveillance
      of diclofenac sodium (Voveran) in 11931 patients. The common conditions were
      rheumatoid arthritis (RA) 28.1%, osteoarthrosis (OA) 24.8%, soft-tissue
      rheumatism 12.4%, cervical spondylosis 6%, ankylosing spondylitis (AS) 3.5%, gout
      2%. East zone had a significantly lower proportion of osteoarthritis (20.9%). The
      age distribution and sex ratios of RA, OA and AS were in line with literature
      reports. The severity of illness was moderate in 62% and duration was more than 6
      months in 50.2%. Data on NSAID usage showed a preponderance of combinations and
      ibuprofen. There were no significant differences in NSAID usage across diseases
      or regions.

PMID- 8307914
TI  - Aortic regurgitation in hypertrophic cardiomyopathy.
AB  - Aortic regurgitation (AR) has been sparsely reported in Hypertrophic
      Cardiomyopathy (HCM) but neither its frequency nor severity has been determined.
      30 patients of HCM were evaluated both by Echocardiography as well as by Cardiac
      Catheterisation and angiography over a 2 year period. Most of them had
      echocardiographically normal aortic cusps. Patients were divided into 2 groups,
      those with AR (Group-I) and those without AR (Group-II). Group-I patients (10
      patients) were significantly older than group-II (51 +/- 4 years vs 38 +/- 3
      years, p < 0.001) and had larger end-diastolic dimension (EDD) (5 +/- 0.5 vs 2.5
      +/- 0.4 cms p < 0.001) and end-systolic dimension (ESD) (3.2 +/- 0.3 vs 2.7 +/-
      0.4 cms p < 0.05) of Left ventricle (LV) in Echo. LC Wall thickness, and LV
      asymmetric septal hypertrophy (ASH) and fractional shortening (FS) were similar
      in the 2 groups. Mitral regurgitation (MR) was more common in Group-I (100% vs
      45% p < 0.001) although there was no difference in left atrial (LA) size between
      the two groups. The HCM patients were compared with a control group of 20 normal
      subjects. None of them (Normal) had any AR murmur or Doppler or angiography
      proved AR. Thus nearly 1/3rd of patients with HCM had mild AR by Doppler or
      aortic root angio and about 10% of HCM patients also had aortic early diastolic
      murmur. The AR most probably results from high velocity systolic blood flow
      causing microscopic or macroscopic damage to the valve cusps.

PMID- 8307915
TI  - Blood pressure trends and life style risk factors in rural India.
AB  - A door to door survey of a random sample of 448 subjects (> or = 15 years of age)
      of Kodamendhi village (near Nagpur) revealed a prevalence of hypertension of 4%
      rising to 19% in more than 60 years age group. One of the main goals of the study
      was to search for social, behavioural and life style risk factors and provide
      baseline information on blood pressure distribution in rural Indian population,
      information regarding which is scarce from Central India. The relationship
      between alcohol consumption, smoking, obesity, education, income and diet
      (assessed by a questionnaire administered by trained interviewers) to blood
      pressure were studied, in multivariate context. Separate multiple linear
      regression analysis, performed in males and females with mean blood pressure
      (MBP) as dependent variable showed that the MBP increased significantly with age
      (p = 0.000) and males had significantly higher MBP than females (p = 0.002). In
      males, BMI (p = 0.000) and alcohol intake (p = 0.008) were significantly related
      to MBP while smokers had significantly lower MBP than non smokers (p = 0.004).
      Per capita income was a significant predictor of MBP in females (p = 0.000).
      There was no relationship with education and diet.

PMID- 8307916
TI  - Ranitidine for the prevention of complications following endoscopic sclerotherapy
      for esophageal varices.
AB  - Thirty one patients with significant esophageal variceal bleed were allocated
      alternately to receive endoscopic sclerotherapy along with ranitidine 300 mg
      daily or endoscopic sclerotherapy alone till eradication of varices. The mean
      sclerotherapy sessions, time and volume of sclerosant required for obliteration
      of varices were similar for the two groups. The esophageal varices were
      eradicated in all the patients except three in sclerotherapy alone group. There
      was statistically significant reduction in frequency of post sclerotherapy
      mucosal ulcers (P < 0.05) after addition of ranitidine to sclerotherapy.
      Rebleeding was not only significantly reduced (P < 0.05) in the sclerotherapy
      with ranitidine group but was minor and did not even require blood transfusion.
      In sclerotherapy alone group rebleeding was controlled by surgery in two patients
      and one died due to massive bleeding. The results of this study suggest a
      beneficial role of ranitidine in reducing post sclerotherapy mucosal ulcers and
      rebleeding. This effect of ranitidine emphasises the role of acid-pepsin in
      pathogenesis of these ulcers and its associated morbidity.

PMID- 8307917
TI  - Liver cysts in patients with autosomal dominant polycystic kidney disease.

PMID- 8307918
TI  - Coronary artery disease in women: a biased medical approach.

PMID- 8307919
TI  - Acromegaly.

PMID- 8307920
TI  - Cephalosporins.

PMID- 8307921
TI  - Diabetic nonketotic hyperglycemia presenting as partial status epilepticus.

PMID- 8307922
TI  - Adult onset medullary cystic disease.

PMID- 8307923
TI  - Isolated splenic tuberculosis.

PMID- 8307924
TI  - Acquired pure red cell aplasia: is chloroquine a culprit?

PMID- 8307925
TI  - Fatal ethylene dibromide ingestion.

PMID- 8307926
TI  - Nifedipine overdose in a 70 year old man.

PMID- 8307927
TI  - Spontaneous reversal of atropine induced delirium in organophosphorus compound
      poisoning: an early sign of re-excretion.

PMID- 8307928
TI  - Kasabach Merrit syndrome with verrucous haemangiomata.

PMID- 8307929
TI  - Neuroacanthocytosis with pure chorea.

PMID- 8307930
TI  - Ruptured amoebic liver abscess: an unusual presentation.

PMID- 8307931
TI  - Subdural hematoma presenting as catatonia.

PMID- 8307932
TI  - Factors modifying plasma activity in diabetic nephropathy.

PMID- 8307933
TI  - Changing trends in the treatment of Salmonella typhi infections in north-western
      India.

PMID- 8307934
TI  - Sickle cell disease in south India.

PMID- 8307935
TI  - Spontaneous left ventricular cavity thrombus in a patient of systemic lupus
      erythematosus.

PMID- 8307937
TI  - Aconite induced cardiac arrhythmias.

PMID- 8307936
TI  - Malaria and Widal reaction.

PMID- 8307938
TI  - Osteogenesis imperfecta--an incidental diagnosis in a girl with tropical
      pulmonary eosinophilia.

PMID- 8307940
TI  - Paramann programme labs.

PMID- 8307939
TI  - Adenosine deaminases in pleural effusions.

PMID- 8307941
TI  - Cardiovascular and respiratory manifestations in tobacco chewers.

PMID- 8307942
TI  - Tropical medicine deserves adequate status in India.

PMID- 8307943
TI  - Descriptive cataloging for collections of medical art.
AB  - Conserving our profession's historical record would be aided by creating a guide
      for recording bibliographical information associated with medical art. A guide of
      this nature should conform to currently accepted national standards for
      bibliographical listings, reflect the cataloging needs of these specialized
      materials, and contain a sample data collection sheet. Such a guide would provide
      a starting point for new or undocumented collections to begin organizing and
      listing their holdings. This article presents a cataloging guide that is specific
      to the needs of collecting medical art and that conforms, in both language and
      structure, to established guidelines for descriptive cataloging.

PMID- 8307944
TI  - Collaboration in support of curriculum media: educational media and video
      production services.
AB  - Video Production Services and the Educational Media Department of the St. Louis
      University Health Sciences Center Library have an interrelated working
      relationship serving the schools of medicine, nursing, and allied health by
      providing videotaped instructional material. This paper details the various
      processes involved from the time a faculty member approaches the librarian in
      search of a specific subject video to the completion of an original production by
      the video professional, with both professionals playing an integral role in the
      provision of high quality curricular material. Our experience in the evolution of
      the process provides other medical libraries or biomedical communications units
      with a framework for successful production delivery.

PMID- 8307945
TI  - Activin-A binds to a heterotrimeric receptor complex on the vascular endothelial
      cell surface. Evidence for a type 3 activin receptor.
AB  - The effect of transfection of the type 2 activin receptor, ACTR2, on binding of
      125I-activin-A to the surface of bovine aortic endothelial cells (BAEC) was
      investigated. BAEC transfected either with full-length ACTR2 or with a truncated
      form of ACTR2 lacking the intracellular kinase domain (ACTR2T) displayed two
      classes of 125I-activin-A binding sites, one of high affinity (Kd = 250-254 pM)
      and one of low affinity (Kd = 6.5-16 nM). Affinity labeling of ACTR2-transfected
      BAEC with 125I-activin-A revealed labeled species of 55, 95, 100, and 160 kDa,
      all four of which were immunoprecipitated by an anti-ACTR2 monoclonal antibody.
      Only the 95- and 100-kDa species, however, were immunoprecipitated following
      denaturation of the affinity-labeled cell lysate with SDS. BAEC transfected with
      an epitope-tagged form of ACTR2T (ACTR2TMyc) displayed intense 55- and 70-kDa
      affinity-labeled forms of the truncated receptor, together with a 160-kDa
      species. As with the full-length receptor, the 160-kDa species associated non
      covalently with ACTR2TMyc. These data indicate that, in vascular endothelial
      cells, ACTR2 forms a high affinity heterotrimeric receptor complex with activin
      binding proteins characteristic of type 1 and type 3 activin receptors, and that
      formation of the complex does not require the kinase domain of ACTR2.

PMID- 8307946
TI  - Interaction of Ras and Raf in intact mammalian cells upon extracellular
      stimulation.
AB  - It has recently been shown that Ras proteins interact directly with Raf
      serine/threonine kinases in vitro and in the yeast two-hybrid system, leading to
      speculation that Raf proteins function as effectors for Ras. Here it is
      demonstrated that the endogenous Raf-1 protein co-immunoprecipitates with Ras
      from mammalian cells when the non-neutralizing anti-Ras monoclonal antibody Y13
      238 is used. The formation of a Ras-Raf complex is absolutely dependent on prior
      treatment of the cells with a stimulus that activates Ras: phorbol ester or anti
      T cell receptor antibody in the case of human peripheral blood T lymphoblasts, or
      epidermal growth factor in the case of Rat-1 fibroblasts. Up to 3% of cellular
      Raf-1 can be found in association with Ras. The association is not competed by
      addition of exogenous GST-Raf to the cell lysates and is therefore unlikely to be
      due to Ras-Raf binding after cell lysis. Specific interaction of Ras and Raf
      therefore occurs in intact mammalian cells in response to stimuli that cause Ras
      to become GTP-bound.

PMID- 8307947
TI  - Characteristics of the internalization signal in the Y543 influenza virus
      hemagglutinin suggest a model for recognition of internalization signals
      containing tyrosine.
AB  - Several proteins, including the hemagglutinin (HA)-Y543 mutant influenza virus
      hemagglutinin, are internalized by clathrin-coated pits but do not have a
      sequence that fits a recently proposed consensus for internalization signals
      containing tyrosine. To determine whether or not the HA-543 signal is a
      degenerate form of the internalization signal found in proteins such as the
      transferrin receptor and mannose 6-phosphate/insulin-like growth factor (IGF) II
      receptor, we have mutated amino acid positions of HA-Y543 shown to be important
      for internalization of the two receptors. Our results indicate that the HA-Y543
      mutant contains a sub-optimum sequence for a tyrosine-based internalization
      signal similar to those found in the receptors for transferrin, low density
      lipoprotein, and mannose 6-phosphate/IGFII. However, amino acids with side chains
      having very different chemical properties functioned well in positions that are
      important for the internalization signal. The variety of amino acid side chains
      found in known internalization sequences suggests that atoms of the polypeptide
      chain backbone may contribute important interactions for binding proteins to
      clathrin coats, with many of the side chains serving mainly to permit these
      interactions, a situation similar to that observed for the binding of peptides by
      histocompatibility proteins.

PMID- 8307948
TI  - Effect of initiation factor eIF-5A depletion on protein synthesis and
      proliferation of Saccharomyces cerevisiae.
AB  - Eukaryotic translation initiation factor eIF-5A (formerly eIF-4D) is thought to
      function in protein synthesis by promoting synthesis of the first peptide bond
      because it stimulates methionyl-puromycin formation in vitro. eIF-5A is encoded
      by two genes (TIF51A and TIF51B) in Saccharomyces cerevisiae; the protein and its
      hypusine modification are essential for cell viability. To analyze the factor's
      function in vivo, we expressed from the repressible GAL promoter a functional but
      unstable eIF-5A fusion protein (R-eIF-5A) with an NH2-terminal arginine which is
      subject to rapid turnover through the NH2-terminal end rule proteolytic pathway.
      When the conditional mutant strain is shifted from galactose to glucose medium,
      the rapid disappearance of R-eIF-5A protein occurs within one generation, causing
      an immediate inhibition of cell growth. However, eIF-5A-depleted cells synthesize
      protein at about 70% of the wild type rate and exhibit only a slight change in
      polysome profiles reflecting a subtle defect in a late step of translation
      initiation. These results suggest that the activity of eIF-5A may not be
      absolutely essential for general protein synthesis. Rather, eIF-5A may be
      selectively required for translation of certain mRNAs and/or may be involved in
      some other aspect of cell metabolism.

PMID- 8307949
TI  - Directed mutagenesis of chloroplast ribulosebisphosphate carboxylase/oxygenase.
      Substitutions at large subunit asparagine 123 and serine 379 decrease CO2/O2
      specificity.
AB  - Chloroplast-encoded large subunits of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (EC 4.1.1.39) are insoluble when separated from the
      holoenzyme or expressed in Escherichia coli, limiting directed mutagenesis to
      prokaryotic enzymes. In the present study, we performed directed mutagenesis and
      chloroplast transformation with the large subunit gene of Chlamydomonas
      reinhardtii. Two separate mutations were created that are known to influence the
      CO2/O2 specificity of prokaryotic enzymes. The asparagine 123 to glycine and
      serine 379 to alanine substitutions gave rise to photosynthesis-deficient mutants
      that synthesize normal levels of holoenzyme. The Vmax for carboxylation was
      reduced more than 95% and the Km(CO2) was increased more than 3-fold for both
      mutant enzymes. Km (O2) was slightly reduced for the glycine 123 enzyme, but
      increased more than 5-fold for the alanine 379 enzyme. CO2/O2 specificity factors
      for both enzymes are decreased by more than 70%. Km values for ribulose 1,5
      bisphosphate are not significantly affected, but binding affinities for the
      transition-state analog 2-carboxy-D-arabinitol 1,5-bisphosphate are reduced. The
      changes brought about by these substitutions in the eukaryotic large subunit are
      different from the changes observed in prokaryotic enzymes.

PMID- 8307950
TI  - Interactions between fibronectin and chondroitin sulfate are modulated by
      molecular context.
AB  - Interactions between fibronectin (FN) and glycosaminoglycans are essential for
      extracellular matrix morphology and cell adhesion. One of the most abundant
      glycosaminoglycans is chondroitin sulfate, and here we show that recombinant FNs
      (deminectins (DN)) containing the carboxyl-terminal cell, heparin, and fibrin
      domains bind specifically to chondroitin sulfate in affinity chromatography
      assays. Using a panel of mutant DNs, important determinants for chondroitin
      sulfate binding have been localized to repeats III13 and III14 within the heparin
      domain. In particular, mutation of an arginine pair in repeat III13 to neutral
      residues ablated binding to chondroitin sulfate as we previously reported for
      heparin (Barkalow, F.J.B., and Schwarzbauer, J.E. (1991) J. Biol. Chem. 266, 7812
      7818). These results, in combination with the ability of heparin and chondroitin
      sulfate to compete for binding to DNs, demonstrate that these two
      glycosaminoglycans interact with similar or overlapping sites in FN. One
      important difference between FN interactions with heparin and chondroitin sulfate
      is that, while FN and DNs bound equally to heparin, FN bound less efficiently
      than DNs to chondroitin sulfate. Reduced binding to chondroitin sulfate was also
      observed with a larger recombinant FN lacking internal repeats III1-7 indicating
      that the amino-terminal region acts to limit binding to the carboxyl-terminal
      domain. Our results demonstrate that interactions between FN and chondroitin
      sulfate are modulated by molecular context.

PMID- 8307951
TI  - Phosphorylation down-regulates the store-operated Ca2+ entry pathway of human
      neutrophils.
AB  - We have reported previously that the chemotactic peptide N-formyl-methionyl
      leucyl-phenylalanine (fMLP) inhibits transiently Ca2+ entry through the plasma
      membrane Ca2+ pathway activated by emptying the intracellular Ca2+ stores
      (Montero, M., Garcia-Sancho, J., and Alvarez, J. (1993) J. Biol. Chem. 268, 13055
      13061). We show here that calyculin A and okadaic acid, inhibitors of protein
      phosphatases 1 and 2A, prevent the spontaneous reversion of the fMLP-induced
      inhibition of the entry of Ca2+ and Mn2+ (used as a Ca2+ surrogate), leading to a
      permanently inhibited Ca2+ entry pathway. At high concentrations or long
      incubation times the phosphatase inhibitors were even able to inhibit the store
      operated Ca2+ entry pathway (SOCP) in the absence of fMLP. Inhibition of SOCP by
      phorbol dibutyrate, which is not reversible, was not modified by phosphatase
      inhibitors. These results provide additional support for the view that fMLP
      inhibits SOCP through phosphorylation of either the SOCP protein or a regulatory
      protein and indicate that dephosphorylation mediated by protein phosphatases 1
      and/or 2A restores the activity of SOCP after inhibition by fMLP. The time course
      of the inhibition of SOCP by fMLP was similar to the one reported previously for
      the transient fMLP-induced phosphorylation of a 47-kDa protein involved in the
      generation of respiratory burst, which was similarly affected by the phosphatase
      inhibitors.

PMID- 8307952
TI  - Effect of acidic ribosomal phosphoprotein mRNA 5'-untranslated region on gene
      expression and protein accumulation.
AB  - Constructions were made from genes encoding ribosomal acidic phosphoproteins YP1
      beta (L44') and YP2 beta (L45) from Saccharomyces cerevisiae in which different
      parts of the 5'-untranslated regions were included. The constructs were inserted
      into centromeric plasmids under the control of the GAL1 promoter and expressed in
      yeast strains in which the genes coding for each acidic protein family, P1 and
      P2, had been disrupted. Deletions in the 5' region of the two genes have been
      found to oppositely affect their expression. Deletion of most of this region
      strongly stimulates the expression of YP2 beta (L45), increasing the translation
      efficiency of the mRNA, and generating a 6-fold excess of protein in the cell. A
      similar deletion in the rpYP1 beta gene represses the expression of the protein,
      reducing drastically the amount of the mRNA in the cell. The overexpression of
      rpYP2 beta affects the cell growth by inhibiting protein synthesis at the level
      of initiation. Reduction of the YP2 beta(L45) overproduction by growing in
      controlled concentrations of glucose abolishes the inhibitory effect. The excess
      protein, probably as a high molecular weight complex, apparently interferes with
      the joining of the 60 S subunit to the initiation complex generating the
      accumulation of polysome half-mers. In addition, the results indicate the
      existence of a regulatory mechanism by which each one of the two acidic proteins
      controls the expression of the other polypeptide. YP1 beta(L44') represses the
      expression of YP2 beta(L45), while this protein stimulates the expression of YP1
      beta(L44').

PMID- 8307953
TI  - Heparin increases the affinity of basic fibroblast growth factor for its receptor
      but is not required for binding.
AB  - The role of heparin or heparan sulfates in the interaction of basic fibroblast
      growth factor (bFGF) with its high affinity receptor were investigated using
      purified extracellular ligand-binding region of FGF receptor-1 (FGFR-1) and
      intact receptors expressed in a myeloid cell line (32D) that does not express
      detectable levels of heparan sulfate proteoglycans or in Chinese hamster ovary
      (CHO) cell mutants defective in heparan sulfate synthesis. The purified
      extracellular domain of FGFR-1 formed complexes with 125I-bFGF both in the
      presence or absence of heparin. Intact FGFR-1 expressed in 32D cells also bound
      the same amount of 125I-bFGF in the presence or absence of heparin when
      saturating concentrations of bFGF were used. Varying the concentration of 125I
      bFGF showed that heparin increased the amount of 125I-bFGF bound at low bFGF
      concentrations and increased the affinity of bFGF for its receptor by about 3
      fold. To eliminate the possibility of alteration of bFGF properties through the
      chemical modification reactions, bFGF was labeled biosynthetically. The binding
      of biosynthetically labeled bFGF to FGFR-1 also did not require heparin. When
      FGFR-1 or FGFR-2 were expressed in mutant CHO cells deficient in heparan sulfate
      synthesis, the cells also bound 125I-bFGF in the absence of heparin, and the
      addition of heparin increased the affinity of bFGF for its receptors 2-3-fold.
      Thus, heparin or heparan sulfate is not required for the binding of bFGF to its
      receptors but increases the binding affinity to a moderate degree. Finally, the
      requirement for heparin in signal transduction through the receptor was
      investigated. Expression of c-fos mRNA was induced by bFGF in 32D cells
      expressing FGFR-1 to the same extent in the presence or absence of heparin.

PMID- 8307954
TI  - Down-regulation of P4501A1 and P4501A2 mRNA expression in isolated hepatocytes by
      oxidative stress.
AB  - We have previously shown that the inflammatory mediator interleukin-1 suppressed
      transcription of CYP1A1 and CYP1A2 mRNAs (Barker, C.W., Fagan, J.B., and Pasco,
      D.S. (1992) J. Biol. Chem. 267, 8050-8055). Since many of the actions of
      inflammatory mediators are mimicked by oxidative stress, we treated isolated
      hepatocytes with 0.25-1.0 mM H2O2 to determine whether expression of these genes
      is also modulated by oxidative stress. Inducer-dependent accumulation of CYP1A1
      and CYP1A2 mRNAs were maximally reduced approximately 50 and 70%, respectively,
      by 1.0 mM H2O2. Run-on transcription analysis suggested that the effect of H2O2
      was mediated transcriptionally. The reduction in CYP1A mRNA levels was not due to
      a reduction in the levels of all mRNAs due to some general toxic effect since
      H2O2 did not reduce glyceraldehyde-3-phosphate dehydrogenase, alpha-tubulin, beta
      fibrinogen, or albumin mRNA levels, and did not increase lactate dehydrogenase
      released into the medium. Insulin-mimicked H2O2 action, reducing the expression
      of both mRNAs, and N-acetylcysteine, which increases intracellular glutathione
      levels, completely reversed the insulin effect on both mRNAs and the H2O2 effect
      on CYP1A1 mRNA, but only partially reversed the H2O2 effect on CYP1A2 mRNA. This
      study indicates that the CYP1A1 and CYP1A2 genes are responsive to oxidative
      stress and that the majority of this responsiveness can be modified by cellular
      redox potential.

PMID- 8307955
TI  - A label selection approach to assess the role of individual amino groups in human
      choriogonadotropin receptor binding.
AB  - Human choriogonadotropin (hCG) was trace-labeled with [3H]acetic anhydride and
      then incubated with transformed murine Leydig cells (MA-10). The bound hormone
      was recovered, subunits (alpha and beta) were separated and then cleaved, and the
      peptides were purified by high performance liquid chromatography. Analysis of the
      labeling patterns of peptides from the initial preparation and the bound hCG
      fraction enabled us to determine the protection factor of several amino groups,
      which is a measure of the effects of acetylation on receptor binding. The largest
      protection factors, indicating lower labeling in the bound fraction, were found
      on beta and involved the alpha-amino group/Lys2 (analyzed together) and Lys104,
      which exhibited 6-fold and 5-fold selections against binding, respectively. Thus,
      acetylation at either of these amino groups does not prevent binding but results
      in selection against hormone association with receptor. Other amino groups were
      analyzed (e.g. Lys122 on beta; the alpha-amino group and lysines 44/45 (analyzed
      as a pair), 51, and 75 on alpha), and the selection factors indicated either no
      change or only modest changes (2-fold) in selection for or against binding. These
      results indicate that the alpha-amino group/Lys2 and Lys104 of the hormone
      specific beta subunit participate, either directly or indirectly, in receptor
      binding.

PMID- 8307956
TI  - Viral long terminal repeat substrate binding characteristics of the human
      immunodeficiency virus type 1 integrase.
AB  - A DNA binding assay was developed for the human immunodeficiency virus type 1
      (HIV-1) integrase. The assay was capable of defining discrete complexes between
      the enzyme and the viral long terminal repeat (LTR) substrate. DNA binding
      reflected the sequence requirements previously demonstrated for the enzyme's 3'
      end processing activity. Binding exhibited a nonlinear dependence on integrase
      concentration, suggesting that the enzyme functions as a multimer. The oligomeric
      state was investigated by UV-photo-cross-linking of integrase-LTR oligonucleotide
      complexes using DNA substrates substituted with 5-bromo-2'-deoxycytidine within
      the integrase recognition sequence. In the absence of divalent cation, integrase
      cross-linked to the LTR oligonucleotide as a single species whose mobility by SDS
      polyacrylamide gel electrophoresis was consistent with the formation of
      tetramers. Using these techniques, analysis of the binding properties of
      integrase mutants demonstrated that the catalytic and sequence-specific DNA
      binding activities of the enzyme are distinct, involving residues within the
      conserved "DD(35)E" and zinc finger motifs, respectively.

PMID- 8307957
TI  - Monoterpene synthases of Pinus contorta and related conifers. A new class of
      terpenoid cyclase.
AB  - A cell-free extract from the xylem of lodgepole pine (Pinus contorta) catalyzes
      the conversion of [1-3H1]geranyl pyrophosphate to a variety of monoterpene
      olefins found in lodgepole pine oleoresin. This monoterpene synthase activity is
      similar to previously described terpenoid cyclases from grand fir (Abies grandis)
      and other higher plants in molecular mass (67 +/- 2 kDa as estimated by size
      exclusion chromatography), Km for geranyl pyrophosphate (7.8 +/- 1.9 microM), and
      isoelectric point (4.75 +/- 0.2 as determined by isoelectric focusing), but the
      cyclases from both lodgepole pine and grand fir are unlike previously
      characterized terpenoid cyclases from angiosperms and fungi, in that they have an
      alkaline pH optimum (pH 7.8), are activated by K+, Rb+, Cs+, or NH+4 (Li+ and Na+
      are not effective), require either Mn2+ or Fe2+ as divalent metal ion cofactors
      (Mg2+ is not effective), and are not protected by the substrate-metal ion complex
      against inhibition by the histidine-directed reagent diethyl pyrocarbonate.
      Chromatography of the pine xylem extracts on a quaternary amino anion-exchange
      resin results in the separation of four similar, but distinct, multiple product
      monoterpene synthases that produce sabinene, beta-phellandrene, 3-carene, and
      beta-pinene as the principal components, respectively. The major cyclase
      (phellandrene synthase) was subsequently purified by hydroxyapatite
      chromatography and electrophoresis. V8 proteolysis provided a peptide map
      significantly different from that obtained with limonene synthase from spearmint
      (Mentha spicata), and limited NH2-terminal sequencing of the phellandrene
      synthase fragments revealed no significant similarity to the deduced amino acid
      sequence of the angiosperm limonene synthase, the only monoterpene cyclase to be
      cloned and sequenced thus far. Furthermore, polyclonal antibodies raised against
      the angiosperm limonene synthase did not detectably cross-react with any proteins
      in extracts from either lodgepole pine or grand fir by immunoblotting analysis.
      In addition to these structural differences between cyclases from conifers and
      herbaceous angiosperms, the unusual pH optimum, mono- and divalent metal ion
      requirement, and reactivity toward histidine carbethoxylation indicate that
      monoterpene cyclases isolated from conifers may also have a different complement
      of active-site amino acid residues involved in substrate binding and catalysis
      than those of terpenoid cyclases previously isolated from angiosperms.

PMID- 8307958
TI  - Biophysical characteristics of Tus, the replication arrest protein of Escherichia
      coli.
AB  - Tus, a DNA-binding protein, mediates arrest of DNA replication in Escherichia
      coli. Tus binds to DNA sequences called Ter sites, located in the terminus region
      of the chromosome, and forms replication-arrest complexes that block movement of
      DNA replication forks in a polar fashion. We have analyzed Tus to determine some
      of its physical parameters and biochemical characteristics. Native Tus had an
      8(20,w) of 3.2, a Stokes' radius of 23 A, an axial ratio of 2, and a molar
      absorption coefficient of 39,700 M-1 cm-1. The data also indicated that Tus
      existed as a monomeric protein in solution and when complexed with its cognate
      DNA binding site. Secondary structure estimated from the circular dichroism
      spectrum suggested that Tus consisted of 40% alpha-helix, 0% beta-sheet, 15%
      turn, and 45% aperiodic structure. The isoelectric point of native Tus (pH 7.5)
      was significantly different than that calculated from its amino acid sequence (pH
      10.1), possibly because the tertiary structure of Tus perturbs the ionization of
      several residues. In addition, partial proteolytic digests of free Tus protein
      did not produce a subfragment of Tus that retained DNA binding activity, but did
      demonstrate that Tus was resistant to proteolysis when complexed with a Ter site.

PMID- 8307959
TI  - Localization of O-glycan initiation, sphingomyelin synthesis, and
      glucosylceramide synthesis in Vero cells with respect to the endoplasmic
      reticulum-Golgi intermediate compartment.
AB  - The identification of an endoplasmic reticulum-Golgi intermediate compartment
      (ERGIC), defined by the 53-kDa transmembrane marker protein ERGIC-53, has added
      to the complexity of the exocytic pathway of higher eukaryotic cells. Recently, a
      subcellular fractionation procedure was established for the isolation of the
      ERGIC from Vero cells (Schweizer, A., Matter, K., Ketcham, C. M., and Hauri, H.
      P. (1991) J. Cell Biol. 113, 45-54) which provides a means to study more
      precisely the compartmentalization of the various enzymic functions along the
      early secretory pathway. Here, we have investigated if O-glycan initiation and
      sphingomyelin synthesis are associated with the ERGIC by analyzing both the
      responsible enzyme activities and their corresponding products. Moreover, the
      synthesis of glucosylceramide, the precursor of most glycosphingolipids, was also
      analyzed. In the purified ERGIC fraction UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferase (GalNAc transferase) was only minimally enriched,
      sphingomyelin synthase was not enriched, and UDP-glucose:ceramide-glucosyl
      transferase specific activity was lower than in the homogenate. On Percoll
      gradients all three enzymes cofractionated with Golgi markers rather than ERGIC
      53. Accordingly, sphingomyelin concentrations were extremely low in the ERGIC
      fraction. Double immunofluorescence localization of core N-acetylgalactosamine,
      the product of GalNAc transferase, by monoclonal antibodies against GalNAc
      Ser/Thr (Tn antigen) revealed only little apparent overlap with ERGIC-53. This
      was particularly evident in brefeldin A-treated cells which showed entirely
      different patterns of Tn antigens and ERGIC-53. The results suggest that in the
      secretory pathway of Vero cells O-glycan initiation and sphingomyelin as well as
      glucosylceramide synthesis mainly occur beyond the ERGIC in the Golgi apparatus.

PMID- 8307961
TI  - Enthalpy-entropy balance and convergence temperatures in protein unfolding.
AB  - We find that isoenthalpic and isoentropic temperatures characterizing the
      unfolding of small globular proteins are linked by a simple relationship, which
      takes into account the occurrence of common values of specific unfolding enthalpy
      and entropy changes. The difference between these temperatures implies that the
      hydration effect favors protein folding over a quite large range of temperatures.

PMID- 8307960
TI  - The human alpha 1(XV) collagen chain contains a large amino-terminal non-triple
      helical domain with a tandem repeat structure and homology to alpha 1(XVIII)
      collagen.
AB  - We have cloned and characterized cDNAs encoding the alpha 1 chain of type XV
      collagen from a human placenta library. Using primer extension cloning we
      extended the cDNAs to the 5' end of the mRNA and determined the complete deduced
      primary structure of the human alpha 1(XV) chain. The polypeptide chain contains
      nine triple helical domains separated by eight non-triple helical regions and
      flanked by large amino-terminal (555 amino acid residues) and carboxyl-terminal
      (256 amino acid residues) non-triple helical domains. Comparison of amino acid
      sequences of the human alpha 1(XV) chain with those of mouse alpha 1(XVIII)
      collagen showed remarkable similarity within both amino- and carboxyl-terminal
      non-triple helical domains. Within the carboxyl third of the amino-terminal
      domain a tandem repeat structure is found with an about 45-amino acid residue
      sequence repeated four times. This amino acid sequence has a strikingly high
      similarity to rat cartilage proteoglycan core protein. Northern blot analysis of
      human embryonic RNA revealed that alpha 1(XV) mRNA is expressed predominantly in
      internal organs such as the adrenal gland, kidney, and pancreas.

PMID- 8307962
TI  - Fusogenic virosomes prepared by partitioning of vesicular stomatitis virus G
      protein into preformed vesicles.
AB  - Virosomes were prepared by the insertion of vesicular stomatitis virus
      glycoprotein, a pH-sensitive fusion protein, into preformed liposomes. The
      fusogenic activity of these virosomes was characterized in cell-free fusion
      assays using liposomal targets. Fusion was monitored by concentration-dependent
      changes in the efficiency of resonance energy transfer between N-(lissamine
      rhodamine B sulfonyl)-phosphatidylethanolamine and N-(4-nitrobenzo-2-oxa-1,3
      diazol)-phosphatidylethanolamine and by electron microscopy. The fusogenic
      activity was dependent on the presence of vesicular stomatitis virus
      glycoprotein, was pH-sensitive, and had a pH threshold of activation similar to
      that of the native virus. The extent of fusion was dependent upon the lipid
      composition of the vesicles. This technique will allow vesicles prepared by any
      method to be made fusogenic.

PMID- 8307963
TI  - 2-Amino-3-ketobutyrate-CoA ligase from beef liver mitochondria. Purification and
      partial sequence.
AB  - 2-Amino-3-ketobutyrate-CoA ligase (EC 2.3.1.29), or aminoacetone synthetase, has
      been purified by a nine-step procedure from 1.0 kg of beef liver to yield 8.8 mg
      of homogeneous enzyme. The homogeneous form of the enzyme, a monomer of M(r) =
      44,000, shows unusually high absorption at 430 nm, with a ratio of absorbance at
      280 and 430 nm of 2.6. On storage a species with an additional absorption peak at
      332 is formed. Neither the 430-nm peak nor the 332-430 ratio is affected by pH or
      substrates. The peak at 430 nm and enzyme activity are both reduced by
      borohydride reduction and treatment with cysteine. The first 21 amino acids at
      the NH2-terminal of the ligase occur in the sequence Ser-Ala-Leu-Ala-Gln-Leu-Arg
      Gly-Ile-Leu-Glu-Glu-Glu-Leu-Glu-Ser-Ile-Arg- Gly-Ala - Gly. No homology is
      detectable in the first 20 amino acids of the Escherichia coli and beef liver
      mitochondria enzymes. However, homology is found around the lysine residue to
      which the pyridoxal 5'-phosphate is attached in the two enzymes. A very
      hydrophobic peptide containing pyridoxal phosphate having the following sequence
      Leu-Leu-Gly-Val-Met-Asp-Gln-Val-Thr-Ile-Ile-Asn-Ser-Thr-Leu-Gly-Lys(P xy)-Ala-
      Leu-Gly-Gly-Ala-Ser-Gly-Gly-Tyr-Thr-Thr-Gly-Pro-Gly-Ala-Leu-Val has been isolated
      from the ligase. Fourteen residues around the lysine to which the pyridoxal 5'
      phosphate is bound are completely identical with the pyridoxal 5'-phosphate
      containing peptide isolated from the E. coli 2-amino-3-ketobutyrate-CoA ligase.

PMID- 8307964
TI  - Conditional activation of cAMP signal transduction by protein kinase C. The
      effect of phorbol esters on adenylyl cyclase in permeabilized and intact cells.
AB  - To understand the convergence of cAMP and protein kinase C signal transduction,
      adenylyl cyclase isozyme identification and biochemical studies were performed on
      the HT4 neural cell line. In HT4 cells, basal cAMP production by adenylyl cyclase
      types I and VI were unaffected by phorbol esters, nor did phorbol esters have any
      effect on forskolin-induced cAMP production. However, phorbol esters
      synergistically increased cAMP production when adrenaline receptors were
      simultaneously activated, indicating a conditional activation of cAMP production
      by phorbol esters. A permeabilized cell preparation was used to analyze the
      mechanism by which phorbol esters were affecting cAMP production. This
      preparation enables G-proteins to be activated directly by GTP gamma S or
      bacterial toxins. In the permeabilized cell preparation, phorbol esters enhanced
      cAMP produced by GTP gamma S-activated G-protein. A stimulatory G-protein pathway
      may be involved since phorbol esters synergistically increased cAMP production by
      cholera toxin, yet had no effect on that produced by pertussis toxin. In this
      cell culture model, phorbol esters stimulate cAMP production only when some
      component of the cAMP cascade is simultaneously activated. Moreover, the pattern
      of modulation suggests that protein kinase C acts on an activated component of
      the second messenger system, such as the G-protein or the coupling of the G
      protein with adenylyl cyclase, and not on the resting state of the protein
      components.

PMID- 8307965
TI  - Characteristics and partial purification of a novel cytosolic, magnesium
      independent, neutral sphingomyelinase activated in the early signal transduction
      of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation.
AB  - Treatment of HL-60 cells with a 1 alpha,25-dihydroxyvitamin D3 induces activation
      of a neutral sphingomyelinase (SMase), resulting in a decrease in sphingomyelin
      (SM) levels and an increase in ceramide levels in a proposed "sphingomyelin
      cycle" of cell regulation (Okazaki, T., Bell, R., and Hannun, Y. (1989) J. Biol.
      Chem. 264, 19076-19080). Cell-permeable synthetic ceramides induce HL-60 cell
      differentiation toward a monocytic lineage without conversion to sphingosine,
      suggesting that ceramide is a lipid mediator of cell differentiation (Okazaki,
      T., Bielawska, A., Bell, R., and Hannun, Y. (1990) J. Biol. Chem. 265, 15823
      15831). In this study, we investigated a novel SMase that was activated 2-2.5 h
      after treatment of cells with 1 alpha,25-dihydroxyvitamin D3. The activated SMase
      was localized to the cytosolic fraction. It was inhibited by copper, ferric iron,
      and zinc and showed optimal activity at pH 7.5. A mixed micellar assay was
      developed for the enzyme, with optimal activity achieved at 12 mol% SM in Triton
      X-100 mixed micelles and at 20 mol% SM in deoxycholate micelles. The activity was
      modestly enhanced by phosphatidic acid, phosphatidylserine, or
      phosphatidylinositol, but not by other major phospholipids. Purification was
      performed by chromatography on DEAE anion-exchange, Q-Sepharose Fast Flow,
      hydroxylapatite, sphingosylphosphocholine affinity, and Superose 12 gel
      filtration columns. Two peaks of activity with molecular masses of 45 and 95 kDa
      were resolved by gel filtration chromatography on Superose 12. The specific
      activities of the purified 45- and 95-kDa enzymes were 2780 and 2790 nmol/mg/h,
      respectively. These data identify a novel cytosolic, magnesium-independent,
      neutral SMase(s) that is activated during cell differentiation.

PMID- 8307966
TI  - Processing of gonadotropin-releasing hormone gene transcripts in the rat brain.
AB  - The precursor of gonadotropin-releasing hormone (GnRH) and the 56-amino acid GnRH
      associated peptide is encoded in an mRNA of about 560 bases in length. This mRNA
      derives from an approximately 4300-base pair-long gene consisting of four
      relatively short exons (denoted 1, 2, 3, and 4) and three large introns (A, B,
      and C). In this study, we characterized the order by which the three introns are
      spliced from the primary transcript and processing intermediates to give rise to
      a mature mRNA and evaluated the potential role of gene transcription and pre-mRNA
      processing in the control of proGnRH mRNA levels in vivo. Nuclear and cytoplasmic
      RNA fractions isolated from rat preoptic area-anterior hypothalamus (POA-AH) and
      basal olfactory area (located rostral to the POA) were analyzed by 1) solution
      hybridization-RNase protection mapping using several RNA probes directed at
      various regions of the proGnRH gene and 2) reverse transcription-polymerase chain
      reaction using several oligonucleotide primers. Both types of analysis showed
      that proGnRH pre-mRNA processing begins with the splicing of intron B from the
      primary gene transcript. Hence, intron B is the ideal target for studying proGnRH
      primary transcript by in situ hybridization. Subsequent splicing of introns A and
      C appeared to take place in two alternative, although not equally prevalent
      pathways. Quantitative analysis indicated that the proGnRH hnRNA species
      constituted, on a mole basis, about 20% of the total gene transcripts in the POA
      AH. The primary transcript alone constituted about 10% of the total gene
      transcripts in the POA-AH and as much as 20% in the basal olfactory area. The
      prospect of blockade of proGnRH hnRNA processing by means of hybridization with
      endogenous antisense RNAs (transcribed from the SH gene on the opposite strand of
      the same DNA locus) did not prove to be likely, as the SH transcripts were
      present at very low levels compared to any of the proGnRH RNA species. We
      conclude that the relatively large pool of proGnRH hnRNA may reflect a high rate
      of gene transcription and/or slow RNA processing.

PMID- 8307967
TI  - The role of cysteine 78 in fluorosulfonylbenzoyladenosine inactivation of rat
      liver S-adenosylhomocysteine hydrolase.
AB  - Inactivation of rat liver S-adenosylhomocysteine hydrolase by the site-directed
      reagent 5'-p-fluorosulfonylbenzoyladenosine (FSBA) is associated with the
      formation of a disulfide bond between Cys-78 and Cys-112 (Takata, Y., and
      Fujioka, M. (1984) Biochemistry 23, 4357-4362; Gomi, T., Ogawa, H., and Fujioka,
      M. (1986) J. Biol. Chem. 261, 13422-13425). To characterize the inactivation
      mechanism more precisely, the properties of four hydrolase proteins mutated at
      Cys-78 or Cys-112 were compared to those of the wild-type enzyme. When Cys-78 was
      mutated to either a serine or an alanine, proteins with greatly reduced enzymatic
      activity were obtained, large effects on kinetic constants were observed, and
      enzymatic activity was not affected by incubation with FSBA. When Cys-112 was
      mutated to either a serine or an alanine, the activity was similar to the wild
      type protein, only small changes in the kinetic constants were observed, and the
      enzyme was inactivated more rapidly upon incubation with FSBA. FSBA inactivation
      of the C112A mutant protein was accompanied by the formation of a disulfide
      between Cys-78 and Cys-52. The data indicate that FSBA initially reacts with Cys
      78 and that Cys-78 has an important role in the structure of the enzyme.

PMID- 8307968
TI  - Acetylcholine mustard labels the binding site aspartate in muscarinic
      acetylcholine receptors.
AB  - Acetylcholine mustard (AChM) is an analogue of acetylcholine (ACh) in which the
      onium headgroup is replaced by a chemically reactive aziridinium moiety. AChM
      aziridinium has agonist activity, but, having bound, reacts with and blocks the
      muscarinic receptor (mAChR) binding site. Purified mAChRs from rat forebrain have
      been specifically labeled with [3H]AChM. The linkage formed is cleaved by
      hydroxylamine, is found within cyanogen bromide (CNBr) peptides with molecular
      masses of approximately 2.4 and 3.9 kDa, and is close to a disulfide-bonded
      cysteine. Edman degradation reveals a site of label attachment 26 residues C
      terminal to a CNBr cleavage site. As in the case of the alkylating antagonist
      analogue [3H]propylbenzilylcholine mustard, these findings indicate that a
      conserved aspartic acid residue in transmembrane helix 3 of the mAChRs,
      corresponding to Asp-105 (m1 sequence), is the site of label attachment.

PMID- 8307969
TI  - Diacylglycerol kinase in receptor-stimulated cells converts its substrate in a
      topologically restricted manner.
AB  - The regulation of diacylglycerol (DG) kinase activity was studied in fibroblasts
      and Jurkat T cells. We questioned whether enzyme activity only depends on
      substrate availability or whether it requires receptor stimulation. To this end,
      we raised DG levels up to 15-fold by treatment of cells with bacterial
      phosphatidylinositol-specific phospholipase C (PLC). In detergent cell lysates,
      DG kinase was readily capable of converting this surplus of DG to phosphatidic
      acid (PA), but in intact cells the enzyme remained inactive. Stimulation of
      fibroblasts with bradykinin or endothelin and Jurkat cells with anti-CD3 resulted
      in DG kinase-mediated formation of PA, but its level was unaffected by PLC
      pretreatment. Likewise, in streptolysin O-permeabilized fibroblasts, where
      bradykinin stimulation in the presence of [gamma-32P]ATP and guanosine 5'-O
      (thiotriphosphate) generates [32P]PA exclusively via DG kinase, PLC pretreatment
      did not affect the amount of [32P]PA formed. We conclude that DG kinase acts on
      DG generated by receptor stimulation, but not on DG generated by exogenous PLC.
      We propose a model in which DG kinase physically associates with endogenous PLC.
      Within this complex, receptor-induced DG would then be transmitted ("channeled")
      from endogenous PLC to the active site of DG kinase, whereas excess DG generated
      randomly in the plasma membrane by bacterial PLC is inaccessible to this
      catalytic site.

PMID- 8307970
TI  - Formation and release of a peroxisome-dependent arachidonic acid metabolite by
      human skin fibroblasts.
AB  - Human skin fibroblasts labeled with [5,6,8,9,11,12,-14,15-3H]arachidonic acid
      produce a radioactive metabolite that has a shorter retention time on reverse
      phase high-performance liquid chromatography than arachidonic acid. This product
      is not retained in the cells; it is released entirely into the extracellular
      fluid in a time-dependent manner. The metabolite does not cochromatograph with
      any of the eicosanoid standards, and its formation is not prevented by the
      addition of cyclooxygenase, lipoxygenase, or cytochrome P-450 inhibitors. The
      compound is not produced by fibroblasts labeled with [1-14C]arachidonic acid,
      suggesting that it is formed through an oxidative process. Chemical analyses
      indicated that the metabolite is 4,7,10-hexadecatrienoic acid (16:3). Peroxisome
      deficient human skin fibroblasts did not produce 16:3, indicating that it
      probably is formed through peroxisomal beta-oxidation. Human umbilical vein
      endothelial cells and porcine pulmonary artery smooth muscle cells also release
      radioactive 16:3 following labeling with [3H]arachidonic acid. Therefore, the
      production of this metabolite is not limited only to fibroblasts. The fact that
      16:3 is released into the extra-cellular fluid suggests that it may be a new type
      of lipid mediator derived from arachidonic acid, formed through a peroxisome
      dependent oxidative process.

PMID- 8307971
TI  - Long-term expression of c-H-ras stimulates Na-H and Na(+)-dependent Cl-HCO3
      exchange in NIH-3T3 fibroblasts.
AB  - In a study of intracellular pH (pHi) regulation, we compared c-H-ras-transformed
      fibroblasts (FT9s) with parental NIH 3T3 cells. Cells were grown on a coverslip
      and placed in a flow-through cuvette; pHi was monitored using a fluorescent dye.
      Whether cells were in a CO2-free or CO2-containing solution, steady-state pHi was
      approximately 0.5 higher in FT9s than in 3T3s. Rates of pHi recovery from acid
      loads in the presence of CO2 indicate that total net acid extrusion (Jtotal) was
      far greater in FT9s than 3T3s in the pHi range 6.3-7.4. In both FT9s and 3T3s,
      pHi recovery was blocked by removing Na+. In FT9s, most of Jtotal was blocked by
      ethyl isopropyl amiloride (EIPA) and was probably due to Na-H exchange. A smaller
      component was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS)
      and required Cl- and was probably due to Na(+)-dependent Cl-HCO3 exchange. In
      3T3s, the DIDS-sensitive and Cl(-)-dependent components of Jtotal were very
      small. The dominant acid-extruder in 3T3s appears to be a Na-H exchanger
      insensitive to 50 microM EIPA. We determined the flux-pHi relationships for both
      the Na-H and Na(+)-dependent Cl-HCO3 exchangers in both FT9s and 3T3s. p21ras
      alkaline shifts the pHi profile of each transporter by approximately 0.7, without
      affecting the Vmax. These shifts in the flux-pHi relationships provide a
      mechanism for the large increase in steady-state pHi produced by long-term
      expression of p21ras.

PMID- 8307972
TI  - Caldesmon enhances the binding of myosin to the cytoskeleton during platelet
      activation.
AB  - Activation of platelets with physiological agents results in distinct cellular
      events such as shape change, cell aggregation, granule secretion, and clot
      retraction. Translocation of soluble cytoplasmic myosin to the actin cytoskeleton
      occurs during activation and may be involved in some of these physiological
      responses. Phosphorylation of the 20,000-dalton myosin light chain occurs in
      parallel with myosin translocation; however, exceptions to this correlation have
      been reported. The present study tests the hypothesis that the actin- and myosin
      binding protein, caldesmon, is required for this enhanced binding of myosin to
      the actin cytoskeleton. Caldesmon, a putative regulatory protein found in non
      muscle and smooth muscle cells, binds actin and myosin simultaneously to form an
      actin-caldesmon-myosin complex and "tethers" myosin to actin in a manner that
      promotes, rather than inhibits, translocation of actin filaments relative to
      myosin. In this study, we demonstrated that a purified myosin-binding fragment of
      caldesmon competitively blocks caldesmon-dependent tethering in an in vitro
      motility assay and that this effect is prevented by phosphorylating the fragment.
      More importantly, we demonstrated that the unphosphorylated, but not the
      phosphorylated, fragment displaces myosin from the cytoskeleton of activated
      platelets; this suggests that caldesmon enhances the binding of myosin to the
      cytoskeleton during platelet activation.

PMID- 8307973
TI  - 3'-O-(5-fluoro-2,4-dinitrophenyl)-ATP exclusively labels Lys-492 at the active
      site of the sarcoplasmic reticulum Ca(2+)-ATPase.
AB  - Sarcoplasmic reticulum vesicles were labeled with 40 microM 3'-O-(5-fluoro-2,4
      dinitrophenyl)-ATP (FDNP-ATP) at 25 degrees C and pH 7.0 for 4 h. The Ca(2+)
      ATPase was inhibited strongly. The enzyme was almost completely protected either
      by 20 mM Mg.ATP or by 50 mM acetyl phosphate against this inhibition. Pi gave no
      protection. There was a linear relationship between the extent of this inhibition
      and the Mg.ATP-sensitive part of the content of bound FDNP-ATP. Extrapolation
      showed that the enzyme is completely inhibited by Mg.ATP-sensitive binding of 3.6
      nmol of FDNP-ATP/mg of the vesicle protein. This value is in good agreement with
      the content of the phosphorylation site (3.3 nmol/mg of the vesicle protein) in
      the vesicles used. These findings indicate that binding of 1 mol of FDNP-ATP per
      mol of the active sites leads to a complete inhibition of the enzyme. The
      acetylphosphatase activity and phosphorylation with ATP were also strongly
      inhibited by this labeling, whereas phosphorylation with Pi was not inhibited.
      The labeled vesicles were solubilized in SDS, and the Ca(2+)-ATPase was purified
      by size exclusion high performance liquid chromatography. Mapping the labeled
      peptides in the tryptic digest by reversed-phase high performance liquid
      chromatography and sequencing showed that Lys-492 was exclusively labeled with
      FDNP-ATP. These results show that Lys-492 is located in or near the ATP binding
      site and apart from the phosphorylation site and Pi binding site. Molecular
      modeling of FDNP-ATP suggests that this Lys-492 residue is situated on the 3'-OH
      side of the ribose moiety of bound ATP and is close to the alpha-phosphoryl
      group.

PMID- 8307974
TI  - The bacterial periplasmic histidine-binding protein. structure/function analysis
      of the ligand-binding site and comparison with related proteins.
AB  - Bacterial periplasmic binding proteins are initial receptors in the process of
      active transport across cell membranes and/or chemotaxis. Among them, the
      histidine-binding protein (HisJ) has been extensively studied from the
      biochemical, physiological, and genetic points of view. The three-dimensional
      crystal structure of the histidine-binding protein complexed with histidine has
      been determined at 2.5-A resolution by the molecular replacement method using a
      probe structure the previously solved lysine-liganded structure of the lysine-,
      arginine-, ornithine-binding protein (LAO), which shares 70% sequence identity
      with HisJ. The structure is bi-lobate; the two lobes, one bigger than the other,
      are connected by two short strands and are in contact with each other (closed)
      enclosing the histidine. Charged, polar, and non-polar side chains, as well as
      the peptide backbone, are involved in tight binding of the histidine. The bound
      histidine is involved in eight direct hydrogen bonds, six with the bigger lobe
      and two with the smaller lobe, in one potential water-mediated hydrogen bond with
      the bigger lobe, as well as in ionic interactions. The HisJ residues surrounding
      the ligand are the same as the LAO residues interacting with lysine, except for
      residue 52 which is leucine in HisJ and phenylalanine in LAO. The Leu-52 in HisJ
      makes a hydrophobic interaction with the imidazole ring of histidine. Of seven
      mutations affecting the ligand-binding site, five are located in the ligand
      binding site, one in a connecting strand, and one at the domains interface. Based
      on comparisons among related binding proteins, the specific interactions between
      the ligands and the respective binding protein residues are predicted for the
      glutamine-binding protein and the opines-binding protein.

PMID- 8307975
TI  - Enediyne-mediated DNA damage in nuclei is modulated at the level of the
      nucleosome.
AB  - DNA damage in HeLa nuclei and isolated nucleosome core particles has been
      examined for several members of the enediyne family of antitumor antibiotics:
      calicheamicin gamma 1I (CAL), esperamicin A1 (ESP A1), esperamicin C (ESP C), and
      neocarzinostatin (NCS). In nuclei, both NCS and ESP A1 produced DNA damage
      limited to the linker region of the nucleosome, while CAL and ESP C, an analog of
      ESP A1 missing the deoxyfucose-anthranilate moiety, damaged both the core and
      linker DNA. DNA fragments produced by CAL and ESP C in the nucleosome core
      occurred with a 10-11-nucleotide periodicity similar to that produced by DNase I,
      while damage produced by NCS and ESP A1 appeared to be limited to the terminal
      portions of the core DNA. The damage in nuclei is shown to be caused directly by
      the drugs with little contribution from endogenous factors, such as nucleases and
      topoisomerases. Features of drug structure that may limit damage to the
      nucleosome core include the presence of substituents on both sides of the CAL/ESP
      type core, and the presence of an intercalating moiety, such as the naphthoate of
      NCS and possibly the anthranilate of ESP A1.

PMID- 8307976
TI  - Structural and functional characterization of the mouse hepatocyte growth factor
      gene promoter.
AB  - To understand the molecular mechanisms underlying the regulation of hepatocyte
      growth factor (HGF) gene expression and to define the DNA sequences essential for
      its cell-type specific and inducible expression, we have isolated and
      characterized the 5'-flanking region of the HGF gene. A genomic clone containing
      2.8 kilobases of the 5'-flanking region of the HGF gene has been isolated from a
      mouse liver genomic library. Sequence analysis showed that the promoter region of
      the mouse HGF gene contains a noncanonical TATA box (ATAAA). Further analysis of
      the 5'-flanking region revealed a number of putative regulatory elements, such as
      four interleukin-6 response elements (IL-6 RE), two potential binding sites for
      NF-IL6, a TGF-beta inhibitory element (TIE), a cAMP response element (CRE), two
      estrogen response elements (ERE) including one located in the first intron, a
      potential vitamin D response element (VDRE) which overlaps a chicken ovalbumin
      upstream promoter (COUP) transcription factor binding element, two liver-specific
      transcription factor (C/EBP) binding sites, and a B cell- and macrophage-specific
      transcriptional factor binding site (PU.1/ETS). To determine the location of
      sites that may be critical for the function of the HGF promoter, we constructed a
      series of chimeric genes containing variable regions of the 5'-flanking sequence
      of HGF gene and the coding region for chloramphenicol acetyltransferase (CAT).
      Transient transfection of chimeric plasmids demonstrated that the mouse HGF gene
      promoter containing 70 base pairs of the 5'-flanking sequences were active in
      mouse fibroblast NIH 3T3 cells and in human endometrial carcinoma RL95-2 cells.
      This basal transcription activity of the HGF promoter was modulated in NIH 3T3
      and RL95-2 cells by multiple upstream elements. Three positive elements were
      identified at positions -2848 to -2674, -1386 to -1231, and -699 to -274, and
      three negative candidate elements were mapped to positions -1652 to -1386, -964
      to -699, and -274 to -70, respectively. By the combination of a series of 5'-end
      deletion and internal deletion, a cell type-specific negative regulatory element
      in RL95-2 cells was localized to the nucleotide position -964 to -699. Moreover,
      the reporter plasmid containing interleukin 6 (IL-6) response element was
      responsive to IL-6 stimulation in stably transfected NIH 3T3 cells. Our findings
      revealed a complex pattern of transcriptional regulation of the mouse HGF gene
      expression.

PMID- 8307977
TI  - Participation of the small molecular weight GTP-binding protein Rac1 in cell-free
      activation and assembly of the respiratory burst oxidase. Inhibition by a
      carboxyl-terminal Rac peptide.
AB  - NADPH-dependent superoxide generation was activated by anionic amphiphiles plus
      GTP gamma S in a cell-free system consisting of plasma membranes plus recombinant
      p47-phox, p67-phox, and the small GTP-binding protein Rac1. Rac1 was expressed in
      Escherichia coli both as the native form and as a mutant form (Rac1(C189S))
      lacking the prenylation site. When preloaded with GTP gamma S, both Rac proteins
      supported activity to a level comparable to that seen using cytosol. A peptide
      corresponding to the carboxyl-terminal region of Rac1 was used to investigate
      oxidase assembly and activation. Rac1(178-188), but not several control peptides,
      inhibited activity. The peptide inhibited competitively (Ki = 15 microM) with
      respect to Rac1(C189S), while inhibition was noncompetitive or mixed with respect
      to p47-phox and p67-phox. This indicated specific inhibition of the interaction
      of the Rac protein with its target, possibly cytochrome b558. The peptide was
      effective only when added prior to activation with arachidonic acid, suggesting
      that it affects assembly rather than activity. Consistent with this possibility,
      the peptide prevented translocation of p47-phox and p67-phox to the plasma
      membrane. Thus, Rac plays a central role in the assembly of the neutrophil NADPH
      oxidase.

PMID- 8307978
TI  - Autoprocessing of prothiolsubtilisin E in which active-site serine 221 is altered
      to cysteine.
AB  - Subtilisin, an extracellular serine protease from Bacillus subtilis, requires the
      amino-terminal propeptide of 77 amino acid residues for the formation of the
      active enzyme. The propeptide is cleaved upon completion of folding. Serine 221
      at the active center was substituted with cysteine, and the mutant enzyme
      (prothiolsubtilisin) was expressed in Escherichia coli under the control of a T7
      promoter. Prothiosubtilisin, which was produced as inclusion bodies, was
      dissolved in 6 M guanidine HCl and purified to near homogeneity in the presence
      of 5 M urea. The purified protein was renatured by stepwise dialysis. In spite of
      the mutation at the active center, the propeptide was found to be autoprocessed
      with approximately 60-80% efficiency. However, protease activity could not be
      detected in the final product by the spectrophotometric assay. Moreover, the
      cleaved propeptide remained tightly bound to thiolsubtilisin without being
      digested, as evident by SDS-polyacrylamide gel electrophoresis. The amino
      terminal sequence of the processed thiolsubtilisin was determined and proved that
      the propeptide was cleaved at a site identical to that of wild-type
      prosubtilisin. The processed thiolsubtilisin was also found to contain one free
      SH group/molecule. These results unambiguously demonstrate that the processing of
      prosubtilisin occurs by an intramolecular autoprocessing mechanism.

PMID- 8307979
TI  - Characteristics of a negative thyroid hormone response element.
AB  - Thyroid hormones may stimulate or repress transcriptional activity depending upon
      the specific gene. Whereas, a palindromic DNA sequence, TREpal, mediates positive
      regulation by thyroid hormone, the negative response element (nT3RE) remains
      undefined. Therefore, we have examined the DNA sequences that mediate the
      inhibitory effects of thyroid hormone on the transcription of the beta-subunit
      gene of rat thyrotropin (rTSH beta). In rat pituitary tumor cells (GH3),
      transient expression of plasmid constructs containing the putative nT3RE of rTSH
      beta mediated negative regulation by L-triiodothyronine (T3). Since this nT3RE
      contained sequences which resembled a half-site motif of the consensus T3RE and
      the idealized palindrome (TREpal), we tested a construct containing this half
      site motif in the same cells. T3 decreased the activity of this plasmid.
      Cotransfection studies in T3-receptor (T3R)-deficient cells indicated that either
      alpha or beta isoforms of T3R were required for the inhibitory effects of the
      hormone. Both T3R isomers bind to DNA sequences containing the nT3RE from rTSH
      beta DNA or the half-site motif of TREpal. In summary, our results show that the
      repressive properties of T3 are mediated by a nT3RE from rTSH beta. Unexpectedly,
      this motif resembles a half-site component of TREpal which enhances promoter
      activity in response to T3.

PMID- 8307980
TI  - Molecular cloning and expression of the Saccharomyces cerevisiae STS1 gene
      product. A yeast ABC transporter conferring mycotoxin resistance.
AB  - We have cloned a yeast gene that confers a multidrug resistance phenotype on
      Saccharomyces cerevisiae when present in multiple copies. The STS1 (for
      Sporidesmin Toxicity Suppressor) gene encodes a 1511-residue protein whose
      predicted structural organization is characterized by 12 alpha-helical membrane
      segments and two domains containing consensus sites for ATP binding, indicating
      that STS1 is a new yeast ATP-binding cassette (ABC) transporter. A chromosomal
      deletion of STS1 leads to viable delta sts1 cells of both mating types,
      suggesting that STS1 is not essential for cell growth. However, delta sts1 cells
      exhibit supersensitivity to sporidesmin and to other structurally unrelated drugs
      such as cycloheximide. Conversely, overexpression of STS1 leads to increased
      resistance to the same drugs. Although Northern analysis showed that STS1 mRNA is
      present in all yeast cell types, its drastically reduced level in alpha-factor
      arrested cells indicates that expression of STS1 is regulated by mating
      pheromones. Subcellular fractionation and immunoblotting using monoclonal
      antibodies, which recognize a fully functional epitope-tagged Sts1 protein,
      showed that Sts1 is a 175-kDa membrane protein localized mainly to intracellular
      membranes.

PMID- 8307981
TI  - Analysis of a brain-specific isozyme. Expression and chromatin structure of the
      rat aldolase C gene and transgenes.
AB  - Aldolase C mRNA is detected by Northern blot in all fetal tissues in rat; it is
      very abundant in the adult brain and undetectable in the other adult tissues.
      However, reverse transcriptase polymerase chain reaction amplification indicates
      that this gene is not totally repressed in these tissues. A DNase-I
      hypersensitivity site located in a 115-base pair proximal promoter fragment is
      detectable in the brain as well as in other adult tissues. Two MspI/HpaII
      restriction sites located at -3800 and -450 base pairs are demethylated in the
      brain and totally or partially methylated in other tissues. In transgenic mice, a
      12.5-kilobase genomic fragment is strongly and tissue specifically expressed in
      different lines, with conservation of a methylation pattern similar to that of
      the endogenous gene. A chloramphenicol acetyltransferase gene directed by either
      800 or 115 base pairs of aldolase C 5'-flanking sequences is tissue specifically
      expressed in transgenic mice, but the level of expression is very low. This level
      is greatly increased when the transgene consists of a chloramphenicol
      acetyltransferase hybrid gene directed by 5.5 kilobases of aldolase C 5'-flanking
      sequences. We propose therefore that the chromatin structure around the aldolase
      C promoter is accessible in fetal tissues, then remains open in the adult brain,
      where the gene is very active, as well as in tissues in which it is practically
      inactive. The specificity of expression in the brain is conferred by a short 115
      base pair proximal promoter fragment that needs more upstream sequences to be
      fully active.

PMID- 8307982
TI  - G(Anh)MTetra, a natural bacterial cell wall breakdown product, induces
      interleukin-1 beta and interleukin-6 expression in human monocytes. A study of
      the molecular mechanisms involved in inflammatory cytokine expression.
AB  - It is believed that induction of cytokine expression by bacterial cell wall
      components plays a role in the development and course of sepsis. However, most
      attention has been focused on lipopolysaccharide (LPS). We studied the ability of
      N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D- isoglutamyl-m
      diaminopimelyl-D-alanine (G(Anh)MTetra), a naturally occurring breakdown product
      of peptidoglycan that is produced by soluble lytic transglycosylase of
      Escherichia coli, to induce cytokine expression in human monocytes. G(Anh)MTetra
      was found to strongly induce interleukin (IL)-1 beta and IL-6 mRNA expression
      after 2 h and IL-1 beta and IL-6 protein secretion after 48 h of activation. The
      increase in mRNA accumulation was at least partly due to an increase in the
      transcription rates of the respective genes and was accompanied by a strong
      induction of nuclear factor-kappa B and activator protein-1 transcription factor
      expression. Experiments using inhibitors of protein kinase C, protein kinase A,
      and tyrosine kinase-dependent pathways revealed that G(Anh)MTetra-induced IL-1
      beta and IL-6 mRNA expression involves activation of an H7-inhibitable pathway.
      By using the protein synthesis inhibitor cycloheximide, it was shown that
      G(Anh)MTetra-induced IL-6 mRNA expression depends on the synthesis of new
      protein, whereas G(Anh)MTetra-induced IL-1 beta mRNA accumulation does not. When
      responses to G(Anh)MTetra were compared with those to LPS and muramyldipeptide
      (MDP), it was found that the optimal response to G(Anh)MTetra induction was
      similar to that of LPS but significantly higher than the response to MDP.
      Furthermore, maximal G(Anh)MTetra-induced IL-1 beta and IL-6 mRNA expression
      could be enhanced by co-stimulation with LPS or MDP, suggesting that different
      receptors and/or transduction pathways were involved. These results indicate that
      G(Anh)MTetra induces IL-1 beta and IL-6 expression in human monocytes suggesting
      a possible role for G(Anh)MTetra in the release of cytokines during sepsis.

PMID- 8307983
TI  - His64(E7)-->Tyr apomyoglobin as a reagent for measuring rates of hemin
      dissociation.
AB  - To develop an assay for hemin dissociation, His64(E7) was replaced by Tyr in
      sperm whale myoglobin producing a holoprotein with a distinct green color due to
      an intense absorption band at 600 nm. Val68(E11) was replaced by Phe in the same
      protein to increase its stability. When excess Tyr64-Val68 apoglobin is mixed
      with either metmyoglobin or methemoglobin, the solution turns from brown to
      green, and the absorbance changes can be used to measure complete time courses
      for hemin dissociation from either holoprotein. This assay has been used to
      measure rates of hemin dissociation from native metmyoglobin, four myoglobin
      mutants (Ala64(E7), Ala68(E11), Phe68(E11), and Glu45(CD3)), native
      methemoglobin, valence hybrid hemoglobins, and two mutant hemoglobins ((alpha(Gly
      E7)beta(native))2, and (alpha(native)beta(Gly-E7))2). Two kinetic phases were
      observed for hemin dissociation from native human hemoglobin at pH 7.0 and 37
      degrees C. Valence and mutant hybrid hemoglobins were used to assign the faster
      phase (k = 7.8 +/- 2.0 h-1) to hemin dissociation from ferric beta subunits and
      the slower (k = 0.6 +/- 0.15 h-1) to dissociation from alpha subunits. The
      corresponding rate for wild-type metmyoglobin is 0.007 +/- 0.004 h-1.

PMID- 8307984
TI  - Purification and characterization of nitrogenase from a delta nifW strain of
      Azotobacter vinelandii.
AB  - Deletion of the nifW gene in Azotobacter vinelandii yields a strain (DJ224) that
      grows poorly under N2 fixing conditions (Jacobson, M. R., Cash, V. L., Weiss, M.
      C., Laird, N. F., Newton, W. E., and Dean, D. R. (1989) Mol. & Gen. Genet. 219,
      49-57). Here we report the purification of nitrogenase from DJ224. The purified
      Fe protein was indistinguishable from wild-type. The MoFe protein was
      indistinguishable from the wild-type MoFe protein by the criteria of sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, native gel electrophoresis,
      two-dimensional gel electrophoresis, metal analysis, UV/visible and EPR
      spectroscopies. It was different by the criteria of CD spectroscopy and specific
      activities. At a 5:1 molar ratio of Fe protein to MoFe protein, H2 evolution
      under argon was identical to wild-type, C2H2 reduction was inhibited by 27%, N2
      reduction was inhibited by 38%, and CO inhibited H2 evolution by 17%. The above
      data show that the nifW gene product is not required for: 1) detectable
      alteration of the polypeptide; 2) the synthesis of the metal portion of FeMo
      cofactor; or 3) FeMo cofactor insertion. The MoFe protein synthesized in the
      absence of NifW appears to have an alteration near the FeMo cofactor site,
      possibly at homocitrate, which causes differential inhibition of different
      substrates.

PMID- 8307985
TI  - Non-native intragenic reversions selected from Saccharomyces cerevisiae
      cytochrome b-deficient mutants. Structural and functional features of the
      catalytic center N domain.
AB  - A total of 110 revertants have been isolated from two well-characterized
      cytochrome b deficient (mit-) mutants. The mit- mutations are located in an
      extramembranous loop linking the transmembrane alpha-helices IV and V of
      cytochrome b which has been postulated to be part of the catalytic center QN and
      therefore is assumed to be essential for the functioning of the bc1 complex. The
      molecular bases of the reversions were identified by sequencing the cytochrome b
      mRNAs. This allowed us to identify seven new structures of cytochrome b which are
      more or less compatible with its catalytic activity. The secondary mutations
      occurred either at the level of the original site mutation or at adjacent
      positions (region 204-208 of the polypeptide chain), or even at a distance of
      more than 150 amino acids (position 30) suggesting topological interaction
      between these two areas. All the revertants recovered cytochrome contents and
      phosphorylation efficiencies similar to the wild-type ones, albeit differences
      appeared in their specific growth rates and NADH respirations. The failure in bc1
      complex functioning induced by the mutation S206L and its restoration by non
      native reversions are tentatively explained.

PMID- 8307986
TI  - Amino acid replacements at binding sites of monoclonal antibody in the F1-ATPase
      beta subunit from Escherichia coli caused altered subunit interactions.
AB  - The monoclonal antibodies (mAb), beta 12 and beta 31, against the beta subunit of
      Escherichia coli F1-ATPase (Miki, J., Matsuda, T., Kariya, H., Ohmori, H.,
      Tsuchiya, T., Futai, M., and Kanazawa, H. (1992) Arch. Biochem. Biophys. 294, 373
      381) recognize the amino-terminal portion of the maximal 104 residues that are
      not exposed to the surface of the F1-ATPase. To identify the epitope residues
      within these 104 residues, we introduced random mutations in the region, and
      clones without binding activity to the mAb, beta 12 and beta 31, were screened.
      beta subunits defective in binding with mAb beta 12 or beta 31 had amino acid
      replacements at residues 26, 40, 52, 71, and 74 or at residues 40, 41, 43, 44,
      46, and 52, respectively. These residues could be part of the epitope and are
      possibly located close together. We tested the effects of the mutations on
      oxidative phosphorylation-dependent growth by introducing expression plasmids of
      the beta subunit gene with the point mutations into the beta-less mutant, JP17.
      The alpha and beta subunits were missing from the JP17 membranes, and both
      subunits were assembled functionally after expression of the beta subunit was
      induced by introducing the expression plasmid. The replacement of Leu-40 by Pro
      caused the amounts of the alpha and beta subunits on the membranes to be reduced
      less than 20% of the amounts in wild type. The replacement of Glu-41 by Lys
      caused a loss of the alpha subunit on the membranes, without any decrease in the
      beta subunit. These results indicated that the mutation of Leu-40 to Pro affects
      the essential role of the beta subunit in the assembly of the alpha and beta
      subunits on the membranes and that the mutation of Glu-41 to Lys partly affects
      it. The amino-terminal region of the beta subunit, in particular its ternary
      structure, including residues 40 and 41, plays an important role in the molecular
      assembly of the alpha and beta subunits on the membranes.

PMID- 8307987
TI  - Close proximity of Cys64 and Cys140 in the delta subunit of Escherichia coli F1
      ATPase.
AB  - The delta subunit of the F1-ATPase from Escherichia coli contains 2 cysteine
      residues, one at position 64 and the second at position 140 of the amino acid
      sequence. These residues were specifically labeled with sulfhydryl reagents in
      this study without labeling other -SH groups in the enzyme. Modification of
      Cys140 by maleimides such as N-ethylmaleimide or fluorescein maleimide resulted
      in a reconstitutively active enzyme that was indistinguishable from the native
      protein. Labeling of Cys64 with or without concomitant labeling of Cys140
      resulted in a reconstitutively inactive enzyme. The ATPase activity of either
      form of the labeled enzyme was unaffected. However, labeling of Cys64 was
      accompanied by dissociation of the delta subunit from the enzyme. These
      observations suggest a role for the microenvironment of Cys64 in interactions of
      the delta subunit with other subunits in the enzyme. Two types of evidence
      support the conclusion that the 2 cysteine residues of the delta subunit are in
      close proximity. First, incorporation of pyrene maleimide into both delta
      cysteines led to excimer formation. Second, incubation of F1 with 5,5'
      dithiobis(2-nitrobenzoic acid) resulted in quantitative formation of a disulfide
      bond between Cys64 and Cys140, presumably via disulfide interchange. The enzyme
      containing the internally cross-linked delta subunit exhibited an undiminished
      ability to support proton pumping when reconstituted into F1-depleted membrane
      vesicles. The presence of 2 closely apposed cysteinyl residues in the delta
      subunit of the native enzyme places constraints on the type of structure that may
      be proposed for the subunit.

PMID- 8307988
TI  - Cloning, characterization, and functional expression of cDNAs encoding glucose
      transporter proteins from the human parasite Schistosoma mansoni.
AB  - The blood-dwelling adult form of the parasitic worm, Schistosoma mansoni,
      consumes prodigious quantities of host glucose following its transport across the
      tegument. Immunologic or pharmacologic targeting of the relevant transporter
      proteins might form the basis of a schistosome control strategy. Here we report
      the isolation and characterization of three different full-length cDNAs whose
      predicted protein sequences show a high degree of sequence and structural
      similarity to the facilitated diffusion transporter proteins of other animals,
      plants, and bacteria. Functional expression of two cDNAs has been achieved by
      injection of Xenopus oocytes with in vitro derived sense strand RNA. Injected
      oocytes have a significantly increased ability to take up radiolabeled glucose
      analogues over controls. S. mansoni glucose transporters expressed in oocytes
      exhibit stereospecificity for D-glucose, have relaxed specificity for different
      hexoses, exhibit sodium independence, and are markedly inhibited by phloretin and
      cytochalasin B. These two transporters, expressed in oocytes, have a Km for 3-O
      methylglucose of 1.3 and 2 mM. A third glucose transporter homologue cDNA appears
      to derive from a recent pseudogene. Both of the functional S. mansoni glucose
      transporter genes are expressed in larval and adult male and female schistosomes.

PMID- 8307989
TI  - Platelet-activating factor may stimulate both receptor-dependent and receptor
      independent increases in [Ca2+] in human airway epithelial cells.
AB  - Platelet-activating factor (PAF) is a potent mediator which produces a wide range
      of biological responses by binding to specific, high affinity receptors on the
      target cell surface. In addition, we and others have observed cellular responses
      to PAF which are not receptor-mediated. We report here that in HBE-16 human
      bronchial epithelial cells, PAF produces a biphasic increase in [Ca2+]i
      consisting of a rapid initial increase due to release from intracellular stores
      followed by a gradual, sustained phase caused by influx of extracellular Ca2+.
      Under certain conditions, the PAF receptor antagonist L-659,989 completely blocks
      the release of Ca2+ from intracellular stores, suggesting a complete block of the
      receptor-mediated response. Under these same conditions, a residual influx of
      extracellular Ca2+ is observed, suggesting a possible receptor-independent
      response. HBE-16 cells partially metabolize PAF to 1-O-alkyl-2-acetyl-sn-glycerol
      (AAG), a bioactive diacylglycerol analog. Moreover, AAG stimulates Ca2+ influx in
      these cells; the response to AAG is at least 100-fold more potent than that to
      PAF. Taken together, these results suggest that PAF may stimulate Ca2+ influx in
      HBE-16 cells through a receptor-independent pathway mediated by AAG. Thus these
      studies suggest a previously unrecognized dual-pathway regulatory mechanism for
      PAF in the airway.

PMID- 8307990
TI  - A role for Asp-251 in cytochrome P-450cam oxygen activation.
AB  - We have mutated Asp-251, Thr-252, and Lys-178 in cytochrome P-450cam and studied
      their effect on steady-state P-450cam catalysis. The mutation of Asp-251 to Asn,
      which dramatically slows the reaction rate, affects a pH-dependent step in the
      reaction cycle. By examining the individual steps in the reaction cycle, we have
      determined that the effect of the D251N mutation occurs after dioxygen binding.
      Furthermore, our results suggest that the rate-limiting step of the D251N
      reaction cycle is the O-O bond scission event and that this residue also plays a
      crucial role in O-O bond scission in wild-type P-450cam. Based on homology with
      other P-450 enzymes and previous mutagenesis investigations, this role may be
      common to other P-450 systems, and we suggest a mechanism that is consistent with
      the effects of these mutations on enzyme activity.

PMID- 8307991
TI  - Increased expression and genomic organization of a folate-binding protein
      homologous to the human placental isoform in L1210 murine leukemia cell lines
      with a defective reduced folate carrier.
AB  - This laboratory previously described an L1210 leukemia cell line (MTXrA) selected
      for resistance to methotrexate by virtue of impaired transport. In this line, the
      reduced folate carrier had unchanged affinity for methotrexate, was present at
      the cell surface in usual quantity, but did not deliver drug into the cell,
      indicative of a functional defect in the translocation process. In this study, we
      further characterize this cell line along with a subline (F2-MTXrA) selected for
      growth in low levels of folic acid. This subline demonstrates continued high
      resistance to methotrexate and very low influx of [3H]methotrexate and 5
      [3H]formyltetrahydrofolate, indicating the persistence of the defect in the
      reduced folate carrier. Both MTXrA and F2-MTXrA are shown to overexpress FBP2,
      the murine homolog of a folate-binding protein initially isolated from human
      placenta. Compared with parent L1210 cells, Northern analysis revealed FBP2
      expression to be elevated 40-fold in the MTXrA line and 500-fold in F2-MTXrA. The
      large increase in FBP2 expression in the F2-MTXrA line correlates with a 10-fold
      increase in [3H]folic acid membrane surface binding and a 1000-fold decrease in
      the folic acid growth requirement compared with parental L1210 cells. Also, there
      are 20- and 500-fold decreases in the 5-formyltetrahydrofolate growth requirement
      compared with parent L1210 and MTXrA cells, respectively. Finally, the genomic
      organization of the FBP2 locus is presented. The results of Northern analyses
      using probes specific to FBP2 5'-untranslated sequences or to a splice junction
      within this region suggest that the up-regulated FBP2-specific message in F2
      MTXrA utilizes 5'-noncoding sequences distinct from those used in the message
      encoded in L1210 cell lines with low level FBP2 expression. The MTXrA cells
      provide an example of a line selected for primary resistance to methotrexate that
      also exhibits concomitant increased expression of a folate-binding protein.
      Further overexpression of this folate-binding protein (which has homology to that
      initially identified in placenta) provides cells with the ability to meet
      cellular folate needs in a folate-deprived environment.

PMID- 8307992
TI  - Involvement of two sulfur atoms of protein disulfide isomerase and one sulfur
      atom of the DsbA/PpfA protein in the oxidation of mutant human lysozyme.
AB  - Protein disulfide isomerase (PDI) and the DsbA/PpfA protein catalyze the
      oxidation of mutant human lysozyme, L79CC81A, which has two native disulfide
      bonds, Cys6-Cys128 and Cys30-Cys116, a non-native Cys79-Cys95, and 2 free
      cysteine residues at positions 65 and 77. Oxidation of L79CC81A (R-form) yielded
      two isomers, L79CC81A-a (A-form) with tandem-linked Cys65-Cys77 and Cys79-Cys95,
      and L79CC81A-b (B-form) with cross-linked Cys65-Cys79 and Cys77-Cys95 (Kanaya,
      E., Ishihara, K., Tsunasawa, S., Nokihara, K., and Kikuchi, M. (1993) Biochem. J.
      292, 469-476). PDI mainly enhanced the formation of the A- form in the absence of
      oxidized glutathione (GSSG); however, as the concentration of GSSG increased, it
      markedly accelerated the formation of the B-form. In contrast, the DspA/PpfA
      protein mainly enhanced the formation of the A-form, regardless of the presence
      or absence of GSSG. These results and the presumed spatial locations of Cys65,
      Cys77, and Cys79-Cys95 in the R-form suggest that 1 of the half-cystine residues
      in the active site of PDI and the DsbA/PpfA protein can react with 1 of the 2
      free Cys residues of the R-form. The dependence on GSSG of the B-form formation
      with PDI can be explained by the formation of two transient intermolecular
      disulfide bonds between PDI and the R-form and the attack of GSSG by the
      resultant thiolate anion of Cys79 or Cys95. The independence of the reaction with
      the DsbA/PpfA protein from GSSG can be explained by the formation of one
      transient intermolecular disulfide bond. The possible formation of the two
      transient intermolecular disulfide bonds involving two sulfur atoms of PDI and 2
      cysteine or half-cystine residues of the substrate could explain the high
      isomerase activity of PDI.

PMID- 8307993
TI  - Characterization of the actin binding site on smooth muscle filamin.
AB  - We have isolated an NH2-terminal fragment of filamin (M(r) = 70,000) after
      digestion with Staphylococus aureus V8 protease. This fragment was shown to
      interact with filamentous actin in cosedimentation assays. Using cross-reactive
      anti-peptides antibodies directed against the strongly conserved 27-mer sequence
      of alpha-actinin, already implicated as an actin binding site (Kuhlman, P. A.,
      Hemmings, L., and Critchley, D. R. (1992) FEBS Lett. 304, 201-206), we obtained
      evidence suggesting that the homologous sequence of filamin (121-147 sequence) is
      the major element in the interaction with actin. In particular, we used enzyme
      linked immunosorbent assay experiments, in conjunction with a synthetic peptide
      approach, and found that the hydrophobic part of the 27-mer peptide (141-147
      sequence) is largely involved in actin binding. Thus, the filamin sequence 121
      147 (or the alpha-actinin sequence 108-134) and the actin counterpart composed of
      residues 112-125 and 360-372 (we have already implicated) could constitute the
      main interface between actin and these cytoskeletal proteins. However, the
      divergent behavior of filamin and alpha-actinin toward conformational changes of
      actin argues in favor of distinctive interfaces. Finally, the ionic strength
      dependence of the filamin-actin interaction, in contrast to that with alpha
      actinin, strongly suggests that, besides hydrophobic interactions conferred by
      the 27-mer sequence, more hydrophilic region(s) of filamin participate(s) in the
      binding.

PMID- 8307994
TI  - The emergence of a basolateral 1-deoxymannojirimycin-sensitive mannose carrier is
      a function of intestinal epithelial cell differentiation. Evidence for a new
      inhibitory effect of 1-deoxymannojirimycin on facilitative mannose transport.
AB  - We have previously reported that 1-deoxymannojirimycin (dMM), a specific alpha
      mannosidase I inhibitor interfered with the uptake of D-[2-3H]mannose in
      differentiated HT-29 cells (a cell line derived from a human colon
      adenocarcinoma) (Ogier-Denis, E., Trugnan, G., Sapin, C., Aubery, M., and
      Codogno, P. (1990) J. Biol. Chem. 265, 5366-5369). In the present work, we have
      used another cell line derived from a human colon adenocarcinoma, Caco-2 cells,
      which has the capacity to grow and to differentiate on porous filters. We have
      determined that mannose could enter the cells by two distinct transporters. One
      sensitive to dMM, present at the basolateral membrane of differentiated Caco-2
      cells, and one insensitive to the drug localized at the brush border membrane of
      these cells. The basolateral mannose uptake is mediated by a Na(+)-independent
      transporter whereas the apical entry of mannose is under the dependence of Na+.
      We have focused our studies on the basolateral dMM-sensitive mannose carrier.
      Kinetic studies indicated that this facilitative mannose transporter has a Km and
      a Vmax of 55 +/- 8 microM and 0.144 +/- 0.005 mumol/mg of protein/min,
      respectively. This basolateral transporter is clearly distinct from facilitative
      glucose transporters. Moreover, this dMM-sensitive mannose transport accurately
      follows the differentiation process of intestinal epithelial cells as well in
      vitro as shown using Caco-2 cells as in vivo when experiments were done on crypt
      cells and villus cells isolated from rat jejunum.

PMID- 8307995
TI  - Agonist-mediated destabilization of m1 muscarinic acetylcholine receptor mRNA.
      Elements involved in mRNA stability are localized in the 3'-untranslated region.
AB  - The effects of chronic agonist exposure on receptor number (down-regulation) have
      been shown, in part, to be due to effects on mRNA levels. Agonist-mediated
      effects on muscarinic acetylcholine receptor (mAChR) mRNA were investigated in
      Chinese hamster ovary (CHO) cells stably transfected with m1 mAChR gene
      constructs containing the open reading frame and a series of deletions of the
      flanking 3'-untranslated region (3'-UTR). Carbachol (CBC) down-regulated m1
      mAChRs encoded by the construct m1C1, an m1 mAChR transcript containing the
      entire flanking 3'UTR (nucleotides 1526-2622), in a time-dependent fashion with
      maximal decreases occurring by 12 h. Steady-state levels of m1C1 mRNA declined in
      a parallel fashion beginning 6 h after CBC pretreatment. Similar findings were
      obtained with m1C2, a construct which is missing all but 261 bases of flanking 3'
      UTR (nucleotides (nt) 1526-1786). Since the rate of mRNA degradation represents
      an important potential regulatory mechanism to control the level of gene
      expression, we investigated the effects of CBC treatment on m1C1 and m1C2 mRNA
      stability. The half-life of either transcript in untreated cells was
      approximately 14 h, whereas m1C1 and m1C2 transcript half-lives decreased to
      approximately 3 h in cells treated with CBC. Agonist-induced destabilization of
      m1C2 mRNA could be mimicked by phorbol esters in a concentration-dependent manner
      and blocked by the protein kinase inhibitor, H-7. In contrast, m1 mAChR mRNA
      constructs missing nt 1526-1786 of the 3'-UTR (m1C3 and m1C4) did not undergo
      agonist- or phorbol ester-induced destabilization. In the neuroblastoma cell line
      IMR-32, endogenous m1 mAChR mRNA was down-regulated and destabilized following
      CBC treatment. These results demonstrate that agonist-induced mRNA
      destabilization is a potential mechanism for regulating m1 mAChR levels.
      Furthermore, deletion studies identify a 261 base region of the 3'-UTR having the
      potential to form stable stem-loop structures which likely harbors element(s)
      responsible for message destabilization.

PMID- 8307996
TI  - 2-O-methyl-D-mannose residues are immunodominant in extracellular polysaccharides
      of Mucor racemosus and related molds.
AB  - In this study, the structure of the immunodominant carbohydrate epitope of the
      extracellular polysaccharides from mold species belonging to the order Mucorales
      reactive with rabbit IgG antibodies was elucidated. An exo-alpha-D-mannanase
      which was able to abolish the antigenicity of these polysaccharides completely
      was purified and characterized, and the activity was compared with that of an
      alpha-D-mannosidase. Analysis of the monomeric reaction products after enzymatic
      treatment revealed the presence of 2-O-methyl-D-mannose residues. This compound
      is a constituent of the polysaccharides from the mold genera Mucor, Rhizopus,
      Rhizomucor, Absidia, Syncephalastrum, and Thamnidium, and its occurrence in fungi
      has not been reported until now. Two mannan fractions which are highly reactive
      with rabbit IgG were isolated from the extracellular polysaccharides of Mucor
      racemosus and characterized with ethylation analysis. The role of the newly found
      2-O-methyl-D-mannose residues in the immunoreactivity was assessed by specific
      degradation of these mannans with the exo-alpha-D-mannanase and subsequent
      ethylation analysis. It was concluded that the immunodominant carbohydrates
      reactive with rabbit IgG are chains composed of a single terminal non-reducing 2
      O-methyl-D-mannose residue, alpha (1-2)-linked to a short sequence of alpha(1-2)
      linked D-mannose residues.

PMID- 8307997
TI  - Identification of an epidermal growth factor receptor transcriptional repressor.
AB  - Identification of the factors controlling transcription of the epidermal growth
      factor (EGF) receptor gene is essential for understanding regulation of the EGF
      receptor and its overexpression in human carcinomas. In this study, we have
      identified a 60-base pair (bp) region (-919 to -860) relative to the AUG
      translation initiation codon in the EGF receptor 5' promoter that functions as a
      cis-acting EGF receptor transcriptional repressor (ETR). This fragment also acted
      as a repressor when linked to the thymidine kinase promoter. Gel mobility shift
      assays demonstrated that trans-acting factors bind to 60- and 19-bp fragments.
      Competition and chloramphenicol acetyltransferase assays with oligonucleotides
      containing mutations and deletions in this region indicate that the TTCGAGGG
      sequence (-877 to -870) is required for binding as well as repressor activity.
      While the ETR-protected region contains consensus sequences for the E2F binding
      site, no competition was observed with an E2F binding fragment. However, DNA
      protein blot analysis indicates that both the 60- and 19-bp fragments
      specifically bind a 128-kDa polypeptide in extracts from HeLa or A431 human
      epidermoid carcinoma cells. These results suggest that a novel transcription
      factor(s) negatively regulates EGF receptor gene expression through binding to
      the ETR element.

PMID- 8307998
TI  - Assignment of disulfide bonds in corticotropin-releasing factor-binding protein.
AB  - We have previously isolated, cloned, and characterized a protein that
      specifically binds and inactivates the peptide corticotropin-releasing factor.
      The integrity of the disulfide bonds in the binding protein is essential for this
      activity as reduction abolishes the protein's ability to bind corticotropin
      releasing factor. The disulfide arrangement of the 10 cysteines present in the
      mature protein was established by analysis of proteolytically cleaved protein and
      sequence analysis of cystine containing fragments. A pattern is observed where
      each cysteine is connected to the next one in a sequential manner. Inspection of
      the genomic DNA encoding for this protein reveals that four of the domains
      defined by disulfide linkage coincide with four different exons.

PMID- 8307999
TI  - Free radical-induced generation of isoprostanes in vivo. Evidence for the
      formation of D-ring and E-ring isoprostanes.
AB  - We recently reported the discovery that a series of novel prostaglandin (PG)F2
      like compounds (F2-isoprostanes) are produced in vivo independent of the
      cyclooxygenase as products of free radical-catalyzed lipid peroxidation. F2
      isoprostanes are initially formed in situ from arachidonic acid esterified to
      phospholipids and then released preformed. We have now investigated whether
      PGD2/E2-like isoprostanes are also produced by rearrangement of the PGG2-like
      intermediates involved in isoprostane formation. Using a variety of approaches
      utilizing mass spectrometry, compelling evidence was obtained for the presence of
      D2/E2-isoprostane-containing phosphospholipids in the liver (85 +/- 33 ng/g of
      liver) and free D2/E2-isoprostanes in the circulation (215 +/- 90 pg/ml) of rats
      treated with CCl4 to induce lipid peroxidation. In untreated rats, levels of
      D2/E2-isoprostanes esterified in liver phospholipids were much lower (0.90 +/-
      0.10 ng/g), and free compounds could not be detected in the circulation (< 5
      pg/ml). Interestingly, one of the E2-isoprostanes that would be expected to be
      formed in abundance, 8-epi-PGE2, was found to be a potent renal vasoconstrictor,
      and these effects could be abrogated by SQ29548, a thromboxane receptor
      antagonist. Further understanding of the biological consequences of the formation
      of these novel compounds and factors that influence their formation may provide
      valuable insights into the pathophysiology of oxidant injury.

PMID- 8308000
TI  - Activation of beta-isozyme of protein kinase C (PKC beta) is necessary and
      sufficient for phorbol ester-induced differentiation of HL-60 promyelocytes.
      Studies with PKC beta-defective PET mutant.
AB  - 12-O-Tetradecanoylphorbol-13-acetate (TPA) induces growth arrest and
      differentiation of a number of leukemia cell lines including HL-60 human
      promyelocytic leukemia. We investigated the involvement of protein kinase C (PKC)
      isotypes in phorbol ester-induced differentiation using the phorbol ester
      tolerant PET mutant of HL-60 cells, which (in contrast to the parent phorbol
      ester-sensitive (wild-type) S variant of HL-60 cells) does not growth-arrest,
      become adherent, or undergo apoptosis when exposed to TPA (Macfarlane, D. E.,
      Gailani, D., and Vann, K. (1988) Br. J. Haematol. 68, 291-302). In comparison to
      S cells, we found that proliferating PET cells markedly underexpress mRNA for PKC
      beta, but do express PKC alpha and PKC delta. The PKC beta-selective activator 12
      deoxyphorbol 13-phenylacetate 20-acetate induces growth arrest, adherence,
      surface expression of CD11a, and apoptosis in S cells, but not in PET cells.
      Expression of PKC beta in PET cells can be restored by exposing them to
      dihydroxyvitamin D3, and this treatment restores the ability of subsequently
      added 12-deoxyphorbol 13-phenylacetate 20-acetate or TPA to induce immediate cell
      adherence and growth arrest of PET cells. These data led us to conclude that
      activation of PKC beta is both necessary and sufficient for phorbol ester-induced
      growth arrest and adherence in these myeloid cells.

PMID- 8308001
TI  - Assignment of the binding site for tissue plasminogen activator on human
      fibronectin.
AB  - The tissue-type plasminogen activator (t-PA) has been found to bind reversibly to
      human fibronectin (Fn). To locate the binding site on Fn for t-PA, the Fn was
      degraded with N-tosyl-L-phenylalanyl chloromethyl ketone-treated trypsin, and the
      resulting fragments were monitored by the enzyme-linked immunosorbent assay
      method for t-PA binding activities. A 20-kDa fragment with t-PA binding activity
      was identified, separated, and purified. It was subjected to further degradation
      with Staphylococcus aureus proteinase V8. An active 10-kDa fragment was finally
      purified by reverse-phase high pressure liquid chromatography on a C3 column. The
      dissociation constants of the binding of Fn and the 10-kDa fragment to t-PA were
      estimated by Scatchard plot to be 1.13 x 10(-8) and 2.08 x 10(-8) M,
      respectively. The 10-kDa fragment was sequenced and proved to be located at the 8
      9th domains of type I homology of Fn. Based on the structural analysis of the 8
      9th domains, a heptadecapeptide corresponding to the sequence Thr535-Glyl551 of
      Fn, which resided at the large disulfide loop of domain (I-9), was designed and
      synthesized. Both the 10-kDa fragment and the synthetic peptide could
      competitively inhibit the binding of Fn to t-PA. The synthetic peptide showed
      about one-tenth of the binding activity of Fn to t-PA with a dissociation
      constant of 1.35 x 10(-7) M and was proved to be the binding region of Fn for t
      PA. In addition, like the intact Fn, both the 10-kDa fragment and the synthetic
      peptide could remarkably enhance the amidolytic activity of t-PA in a dose
      dependent manner, as shown by using S-2288 as a chromogenic substrate.

PMID- 8308002
TI  - Inositol 1,4,5,6-tetrakisphosphate is phosphorylated in rat liver by a 3-kinase
      that is distinct from inositol 1,4,5-trisphosphate 3-kinase.
AB  - Liver homogenates phosphorylated inositol 1,4,5,6-tetrakisphosphate exclusively
      to inositol 1,3,4,5,6-pentakisphosphate. Approximately 30% of this
      phosphorylating activity was associated with the particulate fraction of the
      cell, in contrast to the inositol 3,4,5,6-tetrakisphosphate 1-kinase, which was
      90% soluble. This soluble 1-kinase activity was resolved from the soluble
      activity that phosphorylated inositol 1,4,5,6-tetrakisphosphate by anion-exchange
      chromatography. The two phosphorylating activities were also found to be
      differentially inhibited by inositol 1,3,4-trisphosphate (IC50 for 3-kinase > 100
      microM; IC50 for 1-kinase < 1 microM). Thus, we have demonstrated that inositol
      1,4,5,6-tetrakisphosphate is phosphorylated directly by a 3-kinase, and inositol
      3,4,5,6-tetrakisphosphate is not an obligatory intermediate, in contrast to one
      previous model (Oliver, K. G., Putney, J. W., Jr., Obie, J. F., and Shears, S. B.
      (1992) J. Biol. Chem. 267, 21528-21534). Inositol 1,4,5,6-tetrakisphosphate 3
      kinase was inhibited by inositol 1,3,4,6-tetrakisphosphate (IC50, 1 microM).
      Soluble inositol 1,4,5,6-tetrakisphosphate 3-kinase and inositol 1,4,5
      trisphosphate 3-kinase were resolved by anion-exchange chromatography.
      Furthermore, cDNA clones of two isozymes of inositol 1,4,5-trisphosphate 3-kinase
      from rat and human brain did not phosphorylate inositol 1,4,5,6
      tetrakisphosphate. Thus, these two 3-kinase activities are performed by distinct
      enzymes.

PMID- 8308003
TI  - Irreversible steps in the ferritin synthesis induction pathway.
AB  - The ability of cells to re-repress ferritin synthesis after removal of an
      inducing agent (iron or heme) was investigated. Re-repression was found to be a
      slow process, requiring approximately 4 (after iron removal) to 10 h (after heme
      removal) for completion. Desferrioxamine mesylate (Desferal) had only a slight
      effect on the rate of re-repression, whereas cycloheximide was strongly
      inhibitory, indicating that new protein synthesis is required for re-repression.
      Re-repression occurred at a slow but significant rate in the presence of both
      Desferal and cycloheximide. These results indicate that, in the absence of an
      iron chelator, the induction of ferritin synthesis is essentially irreversible.
      The kinetics of the previously reported covalent modification of IRE-binding
      protein (IRE-BP) were then examined, to see whether this phenomenon might account
      (at least in part) for the irreversibility of induction. It was found that the
      heme- or iron-dependent disappearance of 98-kDa IRE-BP occurred rapidly (within 1
      h), and was equally rapidly reversed upon removal of heme after a 1-h exposure.
      By contrast, after a 4-h exposure to heme, little 98-kDa IRE-BP could be
      regenerated after heme removal. These results suggest that the slow, irreversible
      covalent modification of IRE-BP correlates closely over time with the induction
      of ferritin synthesis. The covalent modification of IRE-BP depends on cell growth
      rate, and is most readily detected in rapidly growing cells.

PMID- 8308004
TI  - Histidine 21 does not play a major role in diphtheria toxin catalysis.
AB  - It has been proposed that the histidine at position 21 (H21) of the diphtheria
      toxin A subunit (DTA) plays an important role in the ADP-ribosyltransferase
      (ADPRT) activity of the toxin. The region of DT encompassing H21 demonstrates
      sequence similarity with other toxins exhibiting ADPRT activity, is located along
      the catalytic cleft of DTA, and when H21 is chemically modified, ADPRT activity
      is abolished. H21 was mutagenized by a polymerase chain reaction-based system
      whereby all alternative amino acids were substituted in place of the histidine.
      The majority of the substitutions virtually abolished enzymatic activity, the
      exception being a mutant in which H21 was replaced with asparagine (DTA-H21N).
      This mutant demonstrated only a slight increase in Km and relatively small
      decreases in both reaction rate (kcat) and catalytic efficiency (kcat/Km).
      Asparagine is a sterically conserved substitution, but its side-chain is unable
      to replace the imidazole group of histidine in general acid-base mechanisms or to
      participate in electrostatic interactions. This suggests that H21 is important in
      maintaining a steric conformation required for catalysis rather than in
      participating in an electrostatic or acid-base type of exchange.

PMID- 8308005
TI  - Similarities between the oxygen-sensing mechanisms regulating the expression of
      vascular endothelial growth factor and erythropoietin.
AB  - The ability to adapt successfully to periods of relative hypoxia is crucial to
      the survival of all higher life forms. Several genes have previously been
      identified which are up-regulated in response to hypoxia; these include the genes
      encoding erythropoietin (Epo), platelet-derived growth factor B chain,
      endothelin, interleukin-1 alpha, ornithine decarboxylase, and vascular
      endothelial growth factor (VEGF). However, the molecular mechanisms by which
      hypoxia is sensed remain enigmatic. In addition, it is unknown whether the genes
      mentioned share a common oxygen-sensing signal transduction pathway. In this
      report we demonstrate multiple similarities between the oxygen-sensing mechanisms
      regulating the expression of VEGF and Epo. The expression of both mRNAs is
      significantly up-regulated by hypoxia and cobalt chloride (CoCl2), and the half
      life of both mRNAs is markedly prolonged by cycloheximide. In addition, hypoxic
      induction of both Epo and VEGF is inhibited by carbon monoxide. As part of our
      investigation into the signal transduction pathway responsible for the hypoxia
      and cobalt induction of these genes, we discovered that the expression of members
      of the jun and fos protooncogene families is also up-regulated early after
      exposure to either of these stimuli. These findings provide support for the
      hypothesis that the mechanism(s) by which hypoxia is sensed at a molecular level
      may be highly conserved and tightly regulated.

PMID- 8308006
TI  - Elongation factor-1 alpha mRNA is selectively translated following mitogenic
      stimulation.
AB  - Stimulation of quiescent Swiss 3T3 cells to proliferate leads to a selective 6
      fold increase in the rate of translation of protein synthesis elongation factor
      eEF-1 alpha. Northern blot and solution hybridization protection studies show
      that levels of eEF-1 alpha mRNA remain constant following serum stimulation,
      demonstrating that eEF-1 alpha transcripts are not degraded following mitogenic
      stimulation and that the increase in eEF-1 alpha synthesis is accounted for by
      pre-existing mRNA. Localization of these transcripts in resting cells shows that
      they are largely distributed equally between stored mRNA protein particles and
      monosomes/disomes. Following serum addition, eEF-1 alpha transcripts present in
      mRNA protein particles redistribute to large polysomes rather than to monosomes
      and disomes as would be expected. The same is true for those transcripts present
      in monosomes and disomes. Salt-shift and translational runoff studies indicate
      that eEF-1 alpha transcripts sedimenting with monosomes and disomes in quiescent
      cells are associated with actively translating ribosomes. The results suggest
      that a specific transcript can move within polysome profile as a function of the
      affinity of translational apparatus for that transcript.

PMID- 8308007
TI  - Casein kinase II preferentially phosphorylates human tau isoforms containing an
      amino-terminal insert. Identification of threonine 39 as the primary phosphate
      acceptor.
AB  - The in vitro phosphorylation of the microtubule-associated protein tau by casein
      kinase II was studied. Purified human brain tau was phosphorylated by casein
      kinase II to a stoichiometry of 0.7 mol of 32P/mol of tau. Individual recombinant
      human tau isoforms were phosphorylated to stoichiometries ranging from 0.2 to 0.8
      mol of 32P/mol of tau. Casein kinase II catalyzed a 4-fold greater incorporation
      of phosphate into the tau isoform containing a 58-amino acid insert near its
      amino terminus (T4L) than the isoforms without the 58-amino acid insert (T3 and
      T4). Phosphopeptide mapping of casein kinase II phosphorylated human tau and
      recombinant tau isoforms suggested that the isoforms containing an amino-terminal
      insert constitute the major substrates for casein kinase II within the tau
      family. The sites of phosphorylation on T4L were identified by digesting
      phosphorylated T4L with the protease Asp-N, separating the peptides by reversed
      phase high performance liquid chromatography, and analyzing the isolated peptides
      by liquid-secondary ion mass spectrometry and solid-phase amino-terminal
      sequencing. Thr39 was identified as the predominant phosphorylation site, which
      is located 5 residues from the amino-terminal insert in T4L. Phosphopeptide
      mapping of tau isolated from LA-N-5 neuroblastoma cells indicates that Thr39 is
      phosphorylated in situ. To our knowledge, this is the first demonstration of a
      differential phosphorylation of the human tau isoforms, with the isoforms
      containing the acidic amino-terminal insert being the preferred substrates of
      casein kinase II.

PMID- 8308008
TI  - Cooperative binding of GA-binding protein transcription factors to duplicated
      transcription initiation region repeats of the cytochrome c oxidase subunit IV
      gene.
AB  - Transcriptional activity of the TATA-less cytochrome c oxidase subunit IV (COXIV)
      gene promoter depends upon two tandemly repeated sequence elements, each mapping
      immediately downstream of major loci of transcriptional initiation. In this
      paper, we demonstrate that binding of the GA-binding protein (GABP) to ets
      sequence motifs within each repeated unit is required for transcriptional
      activation of the COXIV promoter. High affinity binding of GABP to the COXIV
      promoter required both the DNA-binding GABP alpha subunit and the non-DNA-binding
      GABP beta subunit. Binding of the heteromeric GABP complex to sequences
      containing two GABP binding sites was shown to have a 10-20-fold greater affinity
      than to DNA sequences with a single site. GABP binding was necessary for promoter
      function of a 33-base pair fragment of the COXIV initiation region in transfected
      3T3 or COS cells. Binding of GABP to the COXIV initiation region was also
      required for maximal transcriptional stimulation by an upstream Sp1 binding site.
      The initiation region was demonstrated to direct accurate transcriptional
      initiation in vitro, and mutations to the GABP binding sites affected not only
      transcriptional activity but also initiation site selection. These results
      indicate that the initiation region repeats of the COXIV promoter may function as
      GABP-dependent initiator motifs that position mRNA start sites in the absence of
      a TATA box or other promoter elements.

PMID- 8308009
TI  - G protein beta gamma subunits. Simplified purification and properties of novel
      isoforms.
AB  - The beta and gamma subunits of heterotrimeric guanine nucleotide-binding
      regulatory proteins (G proteins) form tightly associated complexes. To examine
      functional differences among the large number of possible combinations of unique
      beta and gamma subunits, we have synthesized and characterized beta gamma
      complexes containing gamma 5 and gamma 7, two widely distributed gamma subunits.
      When either gamma 5 or gamma 7 is expressed concurrently with beta 1 or beta 2
      subunits in a baculovirus/Sf9 cell system, all four subunit complexes support
      pertussis toxin-catalyzed ADP-ribosylation of rGi alpha 1 (where "r" indicates
      recombinant), indicating formation of functional complexes. Each of the complexes
      was purified by subunit exchange chromatography, using the G203A mutant of rGi
      alpha 1 as the immobilized ligand. The purified preparations were compared with
      other recombinant beta gamma subunits, including beta 1 gamma 1 and beta 1 gamma
      2, for their ability to modulate type I and II adenylyl cyclase activities;
      stimulate phosphoinositide-specific phospholipase C beta; support pertussis toxin
      catalyzed ADP-ribosylation of rGi alpha 1 and Go alpha; and inhibit steady-state
      GTP hydrolysis catalyzed by Gs alpha, Go alpha, and myristoylated rGi alpha 2.
      The results emphasize the unique properties of beta 1 gamma 1. The properties of
      the complexes containing gamma 5 or gamma 7 were similar to each other and to
      those of beta 1 gamma 2.

PMID- 8308010
TI  - Mammalian ferrochelatase. Overexpression in Escherichia coli as a soluble
      protein, purification and characterization.
AB  - Ferrochelatase (protoheme ferrolyase, EC 4.99.1.1), a membrane-bound protein,
      catalyzes the terminal step of the heme biosynthesis in all living systems. A
      cDNA encoding the murine ferrochelatase (Taketani, S., Nakahashi, Y., Osumi, T.,
      and Tokunaga, R. (1990) J. Biol. Chem. 265, 19377-19380) has been expressed in
      Escherichia coli, using the alkaline phosphatase promoter. Ferrochelatase was not
      only overexpressed in an active form, but more importantly, was produced as a
      "soluble protein" (i.e. associated with the soluble bacterial protein fraction).
      A simple purification from the ferrochelatase overproducing bacterial strain
      yielded approximately 50 mg of protein/2-3 liters of bacterial culture.
      Recombinant ferrochelatase exhibited identical physical and catalytic properties
      to those of mammalian ferrochelatases. Specifically, the recombinant
      ferrochelatase has iron and porphyrin as substrates, and N-methylprotoporphyrin
      and metal ions (e.g. Hg2+ and Mn2+), as strong inhibitors of its enzyme activity.
      The Km values are 112.5 microM for iron and 95 microM for deuteroporphyrin IX,
      which are in the same range of the Km values determined for the ferrochelatases
      isolated from natural sources. This report describes the overexpression of a
      mammalian ferrochelatase in E. coli, as a soluble protein, and its purification
      from an overproducing strain. The production of a functional and "soluble"
      ferrochelatase has significance for the pursuit of structural and functional
      studies of this enzyme.

PMID- 8308011
TI  - Identification of two regions of beta G spectrin that bind to distinct sites in
      brain membranes.
AB  - This study analyzed the complex interactions of intact spectrin with bovine brain
      membranes by evaluating membrane associations of defined regions of beta G
      spectrin, the subunit responsible for high affinity membrane binding. Two regions
      of beta G spectrin were expressed in bacteria and demonstrated to contain fully
      functional binding site(s) for a subset of spectrin-binding sites in brain
      membranes depleted of peripheral proteins. One region, located near the NH2
      terminus, was comprised of 106-residue repeats and required repeats 2-7 for full
      activity. The other binding domain was located at the COOH terminus, which is the
      most variable between beta G and beta R spectrins, is distinct from the 106
      residue repeats, and contains a pleckstrin homology domain. NH2-terminal beta
      spectrin polypeptides interacted with a membrane site(s) that recognized both
      brain and erythrocyte isoforms of spectrin, was inhibited by calcium/calmodulin,
      and was not blocked by the COOH-terminal polypeptide. The COOH-terminal region
      associated with a membrane site(s) that was specific for brain spectrin, was not
      inhibited by calcium/calmodulin, and was not blocked by the NH2-terminal
      polypeptide. These observations demonstrate membrane association of spectrin with
      at least two independent sites, which differ with regard to regulation by
      calcium/calmodulin and in selectivity for spectrin isoforms.

PMID- 8308012
TI  - Receptor-independent activation of guanine nucleotide-binding regulatory proteins
      by terminal complement complexes.
AB  - Activation of heterotrimeric guanine nucleotide-binding proteins (G proteins) by
      terminal complement complexes (TCC) was investigated on human lymphoblastoid B
      cell line JY25 and its mutant JY5 deficient in glycosylphosphatidylinositol
      anchored proteins. TCC assembly achieved by antibody-dependent activation of C7
      deficient serum reconstituted with C7 increased specific guanosine-5'-(gamma
      thio)triphosphate (GTP gamma S) binding, 4- and 8-fold, in JY25 and JY5
      membranes, respectively, between 2 and 10 min, over the level without C7. TCC
      also increased GTPase activity 5- and 4-fold in JY25 and JY5, respectively,
      between 5 and 10 min. Increased GTPase activity was noted first with C5b-7
      assembly, which increased further with C5b-8 and C5b-9. The presence of G
      proteins in anti-TCC immunoprecipitates of cell lysates was investigated by
      demonstration of G alpha subunit that can be ADP-ribosylated by pertussis toxin
      (PTX). Immunoprecipitated TCC complexes contained a PTX-sensitive 41-kDa Gi
      alpha/Go alpha subunit, as shown by SDS-PAGE and Western blotting. These
      complexes were functionally active as determined by GTP gamma S binding. We have
      further shown that enhanced TCC elimination from the plasma membrane induced by
      TCC-generated signals was inhibited by PTX. In conclusion the biological
      activities induced by TCC in nucleated cells may be mediated in part by
      activation of PTX-sensitive G proteins.

PMID- 8308013
TI  - Regulation of secretion and surface expression of Mac-2, a galactoside-binding
      protein of macrophages.
AB  - Mac-2, a 30-35-kDa galactose-binding protein, is synthesized at similar levels in
      murine peritoneal exudate macrophages whether recruited in response to an
      intraperitoneal pathogen Mycobacterium microti, to sterile inflammatory stimuli
      such as thioglycollate broth, or to concanavalin A. In elicited or activated
      macrophages up to 30% of Mac-2 is constitutively secreted, and secretion is
      stimulated markedly by calcium ionophore A23187. Only thioglycollate-elicited
      macrophages express cell surface Mac-2, and binding is mostly (> 80%) a result of
      affinity for cell surface carbohydrate structures. Mac-2 surface expression is
      markedly reduced upon further activation of thioglycollate-elicited macrophages
      with bacterial lipopolysaccharide in vitro. Polylactosamine structures are
      present on all macrophage populations examined as determined by binding of
      Lycopersicon esculentum lectin, whereas alpha-galactosyl residues detected by
      Griffonia simplicifolia isolectin B4 are expressed only on the thioglycollate
      elicited macrophages, indicating that these residues are the major determinants
      responsible for Mac-2 surface expression. Chemical cross-linking experiments have
      identified binding of endogenous cell-surface Mac-2 to three glycoproteins of
      molecular masses of 92, 125, and 180 kDa containing alpha-galactosyl and
      polylactosamine structures on thioglycollate-elicited macrophages. The restricted
      cell surface distribution of Mac-2 on thioglycollate-elicited peritoneal
      macrophages, a population of recently recruited monocytes, suggests a role(s) in
      early events of macrophage infiltration and tissue fixation such as extravasion
      and cell-matrix interactions.

PMID- 8308014
TI  - Purification of the DNA binding form of dioxin receptor. Role of the Arnt
      cofactor in regulation of dioxin receptor function.
AB  - The basic region/helix-loop-helix dioxin receptor mediates signal transduction by
      dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin). Upon ligand binding the dioxin
      receptor is converted from a latent, non-DNA binding form to a form that directly
      interacts with target genes by binding to dioxin-responsive transcriptional
      control elements. We have purified by conventional and DNA affinity
      chromatographic procedures the ligand-activated, DNA binding form of dioxin
      receptor to examine its architecture and functional properties. We observed that
      the DNA binding activity of the receptor was labile. Most notably, this activity
      was lost following DNA affinity purification. In complementation experiments we
      have identified an auxiliary factor(s) that exhibited very poor, if any,
      intrinsic affinity for the DNA target sequence in vitro but strongly increased
      the DNA binding activity of the purified receptor-containing material identified
      by immunoblot analysis. In a similar fashion the in vitro expressed basic
      region/helix-loop-helix factor Arnt (that has been postulated to modulate the
      nuclear translocation function of the receptor) reconstituted the DNA binding
      function of the purified receptor, and the purified auxiliary factor
      reconstituted receptor activity upon addition to an extract from mutant, Arnt
      deficient hepatoma cells. Conversely, purified dioxin receptor reconstituted DNA
      binding activity in extracts from receptor-deficient hepatoma cells which express
      bona fide levels of Arnt. Interestingly, UV cross-linking studies using a BrdU
      substituted DNA target sequence indicated that primarily the receptor protein was
      bound to DNA. Moreover, we demonstrate that purified receptor or Arnt exhibited
      virtually no detectable affinity for the target sequence individually but, in the
      presence of one another, showed a strong synergy in DNA binding activity in
      vitro. Importantly, simultaneous expression of the receptor and Arnt resulted in
      synergistic induction of gene expression in vivo. These data demonstrate that
      Arnt plays a central role in control of dioxin receptor function by cooperatively
      modulating the DNA binding activity of the receptor in vitro and dioxin-dependent
      transactivation in vivo.

PMID- 8308015
TI  - Phosphorylation of the human estrogen receptor. Identification of hormone
      regulated sites and examination of their influence on transcriptional activity.
AB  - We have used a transient transfection system with a cytomegalovirus-based vector
      expressing high levels of biologically active human estrogen receptor (ER) in COS
      1 cells to study the phosphorylation of human ER and to identify major hormone
      regulated phosphorylation sites. The features of phosphorylation of the wild-type
      ER were very similar to those previously observed for the endogenous ER in
      uterine cells: The ER exhibited a basal level of phosphorylation which was
      increased approximately 3-4-fold by estrogen (estradiol) and by antiestrogens
      (hydroxytamoxifen and ICI164,384), and phosphorylation was increased to an almost
      similar extent by activation of either protein kinase A or C signal transduction
      pathways with cholera toxin plus isobutyl methylxanthine (CT+IBMX) or phorbol
      ester 12-O-tetradecanoylphorbol-13-acetate (TPA), respectively. Phosphoamino acid
      analysis revealed that the phosphorylation occurred exclusively on serine
      residues in all cases. Tryptic phosphopeptide analysis of ER, using a two
      dimensional peptide mapping procedure, revealed similar patterns for ER in cells
      treated with estradiol, antiestrogens or TPA; with CT+IBMX treatment, the same
      phosphopeptides were seen, but the relative phosphorylation of the different ER
      phosphotryptic peptides differed. In ER deleted of the NH2-terminal A and B (A/B)
      domains, estrogen and antiestrogen-stimulated phosphorylations were abolished,
      while the phosphorylation induced by CT+IBMX was maintained. This suggests that
      sites of phosphorylation enhanced by estradiol and antiestrogen, but not those
      induced by CT+IBMX, are located in the A/B domain. These results were further
      confirmed by comparing the tryptic phosphopeptide patterns of wild-type and A/B
      deleted receptor upon estradiol and CT+IBMX treatments, and then by site-directed
      mutagenesis, by substituting alanines for the serine residues in the A/B domain
      (Ser104, Ser106, Ser118, Ser154, and Ser167) involved in known protein kinase
      consensus sequences. Comparison of the tryptic phosphopeptide patterns of wild
      type ER and these mutant ERs allowed us to identify serine 104 and/or serine 106
      and serine 118, all three being part of a serine-proline motif, the preferred
      substrate of proline-directed protein kinase, as major ER phosphorylation sites.
      When tested with two estrogen-responsive reporter gene constructs in several cell
      types, the mutant S104A, S106A, S118A showed a approximately 40% reduction in
      transactivation activity in response to E2, while the mutants S118A and S104A,
      S106A alone showed a approximately 15% decrease in transactivation. Our studies
      identify several serines in the NH2-terminal portion of the human ER as being
      major hormone-regulated phosphorylation sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308016
TI  - Expression of a differentiation antigen and poly-N-acetyllactosaminyl O-glycans
      directed by a cloned core 2 beta-1,6-N-acetylglucosaminyltransferase.
AB  - Chinese hamster ovary (CHO) cells do not contain detectable amounts of core 2
      beta-1,6-N-acetylglucosaminyltransferase, C2GnT, and thus lack various
      modifications in their branched O-linked oligosaccharides. In the present study,
      the O-linked oligosaccharides and the occurrence of a differentiation antigen
      were analyzed in CHO cells stably transfected with cDNA encoding human
      leukosialin alone (CHO-leu) or with cDNAs encoding both leukosialin and C2GnT
      (CHO-leu.C2GnT). The analysis of O-glycans, released from [3H]glucosamine-labeled
      cells, revealed that CHO-leu cells synthesize O-glycans with a Gal beta 1-
      >3GalNAc backbone, whereas CHO-leu.C2GnT cells synthesize in addition O-glycans
      with a Gal beta 1-->3(Gal beta 1-->4GlcNAc beta 1-->6)GalNAc backbone. Moreover,
      CHO-leu.C2GnT cells express poly-N-acetyllactosaminyl extensions from the GlcNAc
      beta 1-->6 branch in O-glycans, while CHO-leu cells express no detectable amount
      of poly-N-acetyllactosaminyl O-glycans. It was also demonstrated that leukosialin
      in CHO-leu.C2GnT cells is recognized by the T305 monoclonal antibody, while the
      same antibody did not react at all with CHO-leu cells. In addition, the transient
      expression cloning scheme using the T305 monoclonal antibody as a selectin marker
      and COS-1 cells, which endogenously express C2GnT as recipient cells, resulted in
      the isolation of cDNA encoding leukosialin. These results indicate that C2GnT
      determines the expression of poly-N-acetyllactosamines in O-glycans and together
      with leukosialin, an onco-differentiation antigen recognized by the T305
      antibody.

PMID- 8308017
TI  - Saccharomyces cerevisiae Hsp104 protein. Purification and characterization of ATP
      induced structural changes.
AB  - Heat-shock proteins (hsps) function in a variety of ways to help cells and
      organisms cope with environmental changes. One class of hsps, the Hsp100
      proteins, is especially important for tolerance to a variety of extremely
      stressful conditions (e.g. high temperatures or high concentrations of ethanol).
      To begin to characterize the mechanism of action of Hsp100 proteins, we have
      initiated an in vitro analysis of the Saccharomyces cerevisiae Hsp104 protein.
      Here, we report the purification and initial structural characterization of the
      wild-type protein and three variants carrying mutations in the two ATP-binding
      site consensus elements. As demonstrated by both gel filtration chromatography
      and by cross-linking studies with glutaraldehyde, Hsp104 forms a homohexameric
      particle. By electron microscopy, these particles are ring-shaped and reminiscent
      of proteins in the Hsp60 and TF55/TCP families. In contrast to these other
      proteins, Hsp104 forms single rings, each containing only six subunits. More
      strikingly, the assembly and maintenance of Hsp104 particles are dependent upon
      the presence of adenine nucleotides. Oligomerization appears to primarily depend
      upon the second of the two ATP-binding sites in the protein.

PMID- 8308018
TI  - Amplification of an adenylosuccinate synthetase gene in alanosine-resistant
      murine T-lymphoma cells. Molecular cloning of a cDNA encoding the "non-muscle"
      isozyme.
AB  - Adenylosuccinate synthetase (EC 6.3.4.4) catalyzes the initial step in the
      conversion of IMP to AMP. Two isoforms of this enzyme have been observed in
      vertebrates. A muscle isozyme is highly abundant in cardiac and skeletal muscle
      tissue and is thought to play a role in muscle energy metabolism. The non-muscle
      isozyme, which is present at low levels in most tissues, likely functions in de
      novo AMP biosynthesis. The analysis of the non-muscle isozyme has been hampered
      by its low abundance and instability during purification. In this study a genetic
      selection scheme was used to generate a murine T-lymphoma cell line which was at
      least 100-fold enriched for the non-muscle isozyme, as a result of amplification
      of the non-muscle synthetase gene. This cell line made possible the purification
      of the non-muscle isozyme, and the subsequent isolation of isozyme-specific
      peptides. Based on peptide sequence information a degenerate oligonucleotide
      probe was designed and used to screen a mouse kidney cDNA library. A 1.5-kilobase
      cDNA encoding the non-muscle isozyme was cloned and found to contain an open
      reading frame of 1368 base pairs encoding 456 amino acids. Gene transfer
      experiments showed that the cDNA encoded a 50-kDa protein, the size expected for
      mammalian synthetases, that correlated with the presence of high levels of
      synthetase activity. The deduced amino acid sequence of the mouse non-muscle
      synthetase is approximately 75% identical to the previously reported mouse muscle
      synthetase. Southern blot analysis of mouse genomic DNA with the isozyme-specific
      cDNA probes revealed that the synthetase isozymes are encoded by separate genes.
      The non-muscle gene is expressed in most tissues but is virtually undetectable in
      striated muscle tissues. Three different transcripts (1.7, 2.8, and 3.4
      kilobases) are detected for the non-muscle isozyme which show a similar tissue
      distribution. The availability of a cDNA for the non-muscle isozyme of
      adenylosuccinate synthetase will facilitate further comparative analyses with the
      previously cloned muscle isozyme.

PMID- 8308019
TI  - The peptide product of a 5' leader cistron in the beta 2 adrenergic receptor mRNA
      inhibits receptor synthesis.
AB  - The 5' leader region of mammalian beta 2 adrenergic receptor messenger RNAs
      (mRNA) have a short open reading frame (sORF) preceding the receptor cistron.
      Mutational inactivation of the sORF start codon increased beta 2 receptor
      expression and translation 1.9-fold from beta 2 receptor genes transfected into
      COS-7 cells. sORF inactivation also increased receptor synthesis 2.4-fold in a
      cell-free expression system that synthesizes functional beta 2 receptor in vitro.
      Translational initiation at the sORF was demonstrated both in vitro and in
      transfected COS-7 cells using an epitope-tagged fusion protein. Using the fusion
      protein as a reporter for initiation at the sORF shows that 5' leader mutations
      which increase translation of the sORF decrease receptor translation. Mutation
      analysis of the 5' leader region and peptide coding sequences suggests the
      peptide itself inhibits beta 2 receptor expression. Consistent with this
      hypothesis, a synthetic peptide corresponding to the peptide encoded by the beta
      2 receptor sORF potently inhibits translation in vitro. Our results suggest that
      a nonoverlapping cistron in the beta 2 receptor mRNA 5' leader region is
      translated and the resulting peptide inhibits receptor translation.

PMID- 8308020
TI  - NADP(+)-activable, NAD(+)-specific glutamate dehydrogenase. Purification and
      immunological analysis.
AB  - An NAD(+)-specific glutamate dehydrogenase (NAD-GDH) that is inducible by L
      glutamine was isolated from Achlya klebsiana and purified to electrophoretic
      homogeneity. The enzyme is only partially active in vitro unless NADP+ (an
      activator) is present in both its oxidative deamination and reductive amination
      reactions. This type of enzyme was reported (LeJohn, H.B. (1971) Nature 231, 164
      168) to be widespread among the amorphous group of algae-related fungi classified
      as Oomycota. The enzyme retained its dependence on NADP+ at all stages of its
      purification. NADP+ decreased the Km of substrates 3-fold and increased the Vmax
      4-fold. M(r) of the undernatured enzyme was 480,000, and, denatured, only a
      single subunit of M(r) 120,000 was seen. A polyclonal antibody raised in rabbit
      against purified enzyme subunit excised from SDS-polyacrylamide gel
      electrophoresis gels immunoprecipitated the M(r) 120,000 polypeptide, the
      undenatured enzyme, and a physically distinct polypeptide of M(r) 74,000. The
      antibody, purified against the M(r) 120,000 enzyme subunit as anchored antigen on
      Sepharose, still immunoprecipitated the M(r) 74,000 polypeptide. The M(r) 74,000
      polypeptide was found to be a subunit of a M(r) 220,000 native protein.

PMID- 8308021
TI  - Cloning and analysis of a constitutive heat shock (cognate) protein 70 gene
      inducible by L-glutamine.
AB  - An intronless gene encoding a protein of 652 amino acid residues with an M(r) of
      71,266, showing between 79% and 59% identity in nucleotide sequence with heat
      shock protein 70 (HSP 70) genes of Bremia lactucae (a parasitic Oomycete of
      lettuce) and a wide range of organisms that include humans, was isolated from the
      nonparasitic Oomycete Achlya klebsiana. While the gene appears to be
      constitutively expressed, L-glutamine augmented its expression particularly under
      conditions of nutritional stress. L-Glutamine enhanced the transcription of a 2.4
      kilobase poly(A)+ RNA simultaneously in the same way as it elevated the cellular
      level of the HSP 70-like protein. A polyclonal antibody (affinity-purified)
      raised in rabbit against the purified monomeric (M(r) 120,000) form of an NAD
      specific glutamate dehydrogenase (Yang, B., and LeJohn, H.B. (1994) J. Biol.
      Chem. 269, 4506-4512) immunoprecipitated the HSP 70-like protein, and it was used
      to study the kinetics of induction of this stress-related protein and the effect
      of proteinase inhibitors on its metabolism. By using as probes four partial
      length cDNA clones, nine overlapping DNA fragments of the organism's genome
      carrying the HSP 70-like protein gene were isolated from a genomic library. The
      nucleotide sequence of the gene, including its boundaries, was determined by
      using these genomic clones. The 5'-untranslated boundary of the gene displayed
      the classical nucleotide arrangement of heat shock elements as well as CCAAT and
      TATA box motifs. Within the coding region are the typical conserved amino acid
      heat shock protein signatures 1 and 2 at the predicted locations. By primer
      extension and S1 nuclease protection mapping system, we estimated that the gene
      is probably transcribed into a message of 2.2 kilobases.

PMID- 8308022
TI  - Molecular characterization of an NAD-specific glutamate dehydrogenase gene
      inducible by L-glutamine. Antisense gene pair arrangement with L-glutamine
      inducible heat shock 70-like protein gene.
AB  - The gene for an NAD-specific glutamate dehydrogenase (NAD-GDH) that is
      allosterically activated by NADP+ (non-substrate) was cloned, and its physical
      structure and nucleotide sequence was determined. The gene consists of 9 introns
      and 10 exons; the 10th and largest exon, which is 1863 nucleotides long, is at
      the 3'-end of the gene. The shortest exon of 33 base pairs is the first and is
      located at the 5'-end of the gene. The large exon is in perfect register along
      the complementary strand with a heat shock 70 (HSP)-like protein gene. The NAD
      GDH gene is inducible with L-glutamine, just as the HSP 70-like protein gene
      (LeJohn, H.B., Cameron, L.E., Yang, B., MacBeath, G., Barker, D.S., and Williams,
      S.A. (1994) J. Biol. Chem. 269, 4513-4522). The phenomenon of anti-parallel
      coupling of two genes is named antisense gene pair. By Northern and Western
      blotting techniques, we obtained indirect evidence that the gene is expressed in
      vivo. The gene encodes a protein of M(r) 118,740 which consists of 1063 amino
      acid residues. The 5' and 3' borders of the gene display typical but unproven
      promoter motifs of CCAAT, TATAAT, and AAATAAAA polyadenylation signal bounded by
      a pyrimidine-rich transcription termination-type format. Restriction endonuclease
      site mapping of all the genomic clones isolated that carry most or all of the
      gene, and of the genome itself, gave hybridization patterns that are consistent
      with the interpretation that the organism, Achlya klebsiana, has only one form of
      the gene. 3'-End-labeling of a 5.2-kb XbaI DNA fragment (carrying the antisense
      gene pair) that was then asymmetrically cleaved to produce two single 3'-end
      labeled pieces that were used as probes on L-glutamine-induced cell poly(A)+ RNA,
      showed that the end-labeled DNA equivalent to the HSP 70-like protein mRNA
      hybridized to a 3.4-kb transcript and the end-labeled DNA equivalent to the NAD
      GDH mRNA hybridized to a 2.4-kb transcript.

PMID- 8308023
TI  - Identification of an activity that interacts with the 3'-untranslated region of c
      myc mRNA and the role of its target sequence in mediating rapid mRNA degradation.
AB  - Single or multiple copies of the pentameric motif, AUUUA, are found in the 3'
      untranslated domain of most immediate early mRNAs. A broad body of data links
      this 5-base element to the selective degradation of these mRNAs. However, AUUUA
      motifs are neither always necessary nor always sufficient to tag an mRNA for
      rapid degradation. Here, we describe a cytoplasmic, protease-sensitive factor in
      Balb/c3T3 cells that interacts with the 3'-untranslated region of c-myc mRNA. The
      factor recognizes a 39-base uridine-rich domain adjacent to, but distinct from,
      the c-myc AUUUA motif. In chimeric mRNA constructs, the 39-base binding element
      cooperates with adjacent sequence material to destabilize beta-globin mRNA.

PMID- 8308024
TI  - Nuclear localization of glycosaminoglycans in rat ovarian granulosa cells.
AB  - In rat ovarian granulosa cell cultures, internalized cell surface heparan sulfate
      is processed by either a fast lysosome-mediated pathway or by a slow pathway
      which generates glycosaminoglycan fragments. Cell-associated dermatan sulfate
      proteoglycans also undergo processing through analogous pathways, although the
      slow pathway does not involve endoglycosidic cleavage of the dermatan sulfate
      chains. In the present study we tested whether intracellular glycosaminoglycan
      fragments in rat ovarian granulosa cells were transient residents of the nuclei.
      A technique for isolating nuclei was devised in which cells were lysed with a
      hypo-osmotic extraction buffer containing detergent. Nuclei were then purified by
      conventional methods, and final preparations gave excellent recovery of the
      starting DNA (approximately 90%). The technique was used to isolate
      glycosaminoglycans from nuclei after cells were metabolically radiolabeled with
      [35S]sulfate. The results indicated the possible presence of dermatan sulfate,
      but not heparan sulfate, glycosaminoglycans at this location. Failure to remove
      cell surface proteoglycans with trypsin before preparation of nuclei resulted in
      nuclear contamination with significant amounts of intact dermatan sulfate
      proteoglycans. Nuclei preparations obtained using traditional homogenization
      steps from cells either treated without or with trypsin gave identical results
      except that recoveries of DNA were much lower (approximately 30%). The results
      demonstrate the difficulty in isolating pure nuclei and therefore also of firm
      conclusions pertaining to the nuclear association of glycosaminoglycans.

PMID- 8308025
TI  - Differential expression and regulation of multiple dynamins.
AB  - Dynamin is a GTP-, microtubule-, and phospholipid-binding protein that is
      expressed primarily in brain. In Drosophila, the shibire gene encodes a homologue
      of dynamin; mutations in this gene result in a defect in endocytosis, suggesting
      a function for dynamin in endocytic membrane traffic. In the present study we
      show that there are at least two distinct dynamin genes in mammals whose products
      are referred to as dynamins I and II. The two dynamins are similar to each other
      (79% identity) and are both equally homologous to the Drosophila shibire gene
      product (66% identity). The highest degree of identity between dynamins is
      observed in their N-terminal halves, whereas their C termini exhibit little
      homology. Transcripts of both dynamin genes are subject to at least two
      alternative splicing events, the first of which is identically found in both
      dynamins, whereas the second site of alternative splicing is different between
      the two types of dynamins. The first alternatively spliced sequence of the
      dynamins consists of an interior region that is present in two distinct but
      homologous forms in both dynamins, suggesting alternative use of exons in both
      genes at identical positions. The second site of alternative splicing results in
      the generation of different C termini in dynamin I and in the inclusion or
      exclusion of an interior four-amino acid sequence in dynamin II. The two dynamins
      exhibit remarkable differences in their tissue distribution and regulation.
      Dynamin I is almost exclusively expressed in the central nervous system.
      Conversely, dynamin II is expressed ubiquitously in all tissues tested. Previous
      studies revealed that the GTPase activity of dynamin I is regulated by
      phosphorylation by protein kinase C in nerve terminals. Expression of dynamins I
      and II by transfection in COS cells demonstrates that only dynamin I but not
      dynamin II is a substrate for protein kinase C. Our data suggest a specialization
      in the endocytic functions and the regulation of dynamins between neural and non
      neural tissues in mammals.

PMID- 8308026
TI  - Molecular events in close proximity to the membrane associated with the binding
      of ligands to the Na,K-ATPase.
AB  - The membrane-bound fraction of purified Na,K-ATPase was characterized following
      extensive proteolytic digestion in the presence of various physiological ligands
      which stabilize different conformational states of the sodium pump. There are
      distinctive conformational changes of the protein which are revealed by amino
      terminal amino acid sequence analysis of the digests following sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The changes in cleavage patterns
      result from alterations in domain-domain interactions of the protein. We provide
      evidence in the alpha-subunit for (i) tight interaction between part of the
      cytoplasmic ATP binding domain and the membrane-bound portion of the protein;
      (ii) involvement of the cytoplasmic loop between M2 and M3 in structural
      rearrangements upon phosphorylation or ion binding; (iii) generation of the same
      digested products when either ouabain or potassium (rubidium) is present.
      Similarly, evidence is provided for conformational sensitivity of the
      extracellular domain of the beta-subunit. The position of the tryptic cleavage
      point in the beta-subunit is altered depending on whether the alpha-subunit is
      phosphorylated or whether rubidium ions are occluded. Based upon the
      conformationally dependent patterns of exposure and protection of different
      tryptic cleavage sites in the alpha- and beta-subunits we propose a model for
      intraprotein interactions within the alpha-subunit and between alpha- and beta
      subunits following the binding of physiological ligands to the Na,K-ATPase.

PMID- 8308027
TI  - Serum-independent phosphorylation of c-Jun and alterations in AP-1 components by
      transformation with various oncogenes.
AB  - To understand the mechanisms regulating the transactivating activity of Jun/AP-1,
      we analyzed alterations in c-Jun induced by growth stimulation and cell
      transformation. Serum stimulation of quiescent NIH3T3 cells induced a marked
      increase in phosphorylation of c-Jun in its amino-terminal activation domain. On
      the other hand, this domain was highly phosphorylated, in a serum-independent
      manner, in cells transformed with various oncogenes, including active c-raf-1, v
      src, active Ha-ras, and active erbB-2. There were no obvious differences in the
      phosphorylation states of c-Jun in exponentially growing normal and transformed
      cells. However, in the exponentially growing state, the TRECAT activity in
      transformed cells was markedly higher than that in normal cells. Gel retardation
      analysis indicated that the AP-1 components in transformed cells were
      significantly different from those in normal cells. These results suggest that
      some other alterations besides phosphorylation of c-Jun are involved in
      enhancement of AP-1 activity in exponentially growing transformed cells.

PMID- 8308028
TI  - Failure to myristoylate the alpha subunit of Gz is correlated with an inhibition
      of palmitoylation and membrane attachment, but has no affect on phosphorylation
      by protein kinase C.
AB  - The alpha subunit of the GTP-binding regulatory protein Gz has been shown to be a
      substrate for N-myristoylation, palmitoylation, and protein kinase C-catalyzed
      phosphorylation. In the present study, we used an NH2-terminal Gly-->Ala mutation
      to examine the relevance of myristoylation to phosphorylation and anchorage. 293
      cells were transfected with cDNA encoding the normal or mutant form of alpha z.
      Normal alpha z was myristoylated and stably anchored, as assessed by biosynthetic
      labeling and sedimentation with membrane following cell lysis. The mutant form of
      alpha z was not myristoylated and was found predominantly (70-90%) in the
      cytosol. These distributions were corroborated by immunofluorescence microscopy.
      Thus, the NH2-terminal glycine of alpha z appears critical for both
      myristoylation and anchorage. The effects of the Gly-->Ala mutation, however,
      were not confined to these two events. Significantly, the mutation also prevented
      palmitoylation, which presumably occurs at Cys3 in the normal subunit. Therefore,
      it cannot be concluded that myristoylation alone is sufficient for anchorage. The
      protein kinase C-catalyzed phosphorylation of alpha z was demonstrated previously
      to occur near to the NH2 terminus, raising the possibility of an effect of
      phosphorylation on anchorage or, conversely, an effect of myristoylation and/or
      palmitoylation on phosphorylation. The phosphorylation induced in 293 cells with
      phorbol 12-myristate 13-acetate, however, had little impact on anchorage.
      Moreover, the mutant (and thus cytosolic) form of alpha z was as good a substrate
      for phosphorylation as the normal subunit. The fact that myristoylation occurs in
      cells containing alpha z normally, as well as the fact that phosphorylation does
      not influence anchorage, was confirmed with mouse anterior pituitary AtT-20 and
      rat basophilic RBL-2H3 cells. These results demonstrate: 1) that mutagenesis of
      the glycine needed for myristoylation of alpha z also inhibits palmitoylation, 2)
      that the resultant lack of myristoylation and/or palmitoylation does not support
      anchorage, and 3) that neither myristoylation, palmitoylation, nor anchorage is
      required for phosphorylation.

PMID- 8308029
TI  - Structure at the active site of an acylenzyme of alpha-chymotrypsin and
      implications for the catalytic mechanism. An electron nuclear double resonance
      study.
AB  - The structure of the acylenzyme intermediate in the hydrolysis of the specific
      spin-label ester substrate methyl N-(2,2,5,5-tetramethyl-1-oxypyrrolinyl-3
      carbonyl)-L-tryptophan ate and its fluoro analogs catalyzed by alpha-chymotrypsin
      (EC 3.4.21.1) has been determined by electron nuclear double resonance (ENDOR)
      and molecular modeling methods. By a combination of kinetic and cryoenzymological
      methods, we have established conditions to stabilize the spin-labeled acylenzyme
      reaction intermediate. Proton ENDOR features specific for the substrate were
      assigned on the basis of specific deuteration. From the observed ENDOR shifts for
      protons and fluorines that correspond to principal hyperfine coupling components,
      the dipolar hyperfine coupling contributions were calculated to estimate electron
      nucleus distances. With these dipolar separations as constraints, conformations
      of the substrate both free in solution and in the active site of alpha
      chymotrypsin were determined by molecular graphics analysis. Comparison of the
      conformation of the bound substrate to that of the free substrate showed that
      formation of the acylenzyme requires significant torsional alteration in
      substrate structure. The structural relationships between active-site residues
      and the substrate in its ENDOR-assigned conformation are examined with respect to
      the requirements of stereoelectronic rules for formation and breakdown of the
      acylenzyme species.

PMID- 8308030
TI  - Catalytic conformation of carboxypeptidase A. Structure of a true enzyme reaction
      intermediate determined by electron nuclear double resonance.
AB  - The structure of a catalytically competent reaction intermediate of
      carboxypeptidase A (CPA) formed with the specific spin-label ester substrate O-[3
      (2,2,-5,5-tetramethyl-1-oxypyrrolinyl)propen-2-oyl]-L-b eta- phenyllactate
      through application of cryoenzymological methods has been determined by electron
      nuclear double resonance (ENDOR) and molecular modeling. It is shown that the
      reaction intermediate is best identified as a mixed-anhydride acylenzyme
      derivative in which the side chain of Glu-270 is acylated by the spin-label
      substrate, in agreement with previous cryoenzymological and spectroscopic studies
      from this laboratory. From the observed proton ENDOR shifts corresponding to
      principal hyperfine coupling components and assigned by selective deuteration,
      the dipolar hyperfine coupling components were calculated to estimate electron
      proton distances. With these ENDOR-determined distances as constraints, the
      conformation of the substrate free in solution and in the active site of CPA has
      been determined on the basis of torsion angle search calculations. With a
      catalytically active, acetylated form of CPA, we have also assigned the position
      of the side chain of Tyr-198 with respect to the nitroxyl group. The positional
      assignments of both substrate and active-site residues in a true reaction
      intermediate provide important constraints in defining the structural basis of
      action of CPA.

PMID- 8308031
TI  - Peroxovanadium compounds. A new class of potent phosphotyrosine phosphatase
      inhibitors which are insulin mimetics.
AB  - Twelve peroxovanadium (pV) compounds, each containing an oxo ligand, one or two
      peroxo anions, and an ancillary ligand in the inner coordination sphere of V,
      were synthesized, crystallized, and characterized by 51V NMR as > 95% pure. These
      compounds activated the insulin receptor kinase (IRK) of cultured hepatoma cells,
      stimulated lipogenesis in adipocytes, and inhibited the in situ dephosphorylation
      of autophosphorylated IRs and epidermal growth factor receptors of rat liver
      endosomes. The phosphotyrosine phosphatase inhibitory and IRK activating
      potencies of these compounds were linearly correlated (r = 0.74; p < 0.003),
      decayed in parallel in solution, and varied considerably with the ancillary
      ligands within these compounds. In vivo administration activated rat liver IRK in
      parallel with its tyrosine phosphorylation. Co-administration of insulin plus pV
      was markedly synergistic in both respects. pV administration significantly
      decreased circulating insulin and plasma glucose concentrations; the latter to
      levels seen after a dose of insulin yielding > or = 50% occupancy of IRs in vivo.
      Two compounds (mpV(pic) and mpV(2,6-pdc)) displayed relative specificity as
      phosphotyrosine phosphatase inhibitors by inhibiting IR dephosphorylation to a
      significantly greater degree than epidermal growth factor receptor
      dephosphorylation. Thus, pV compounds are the most potent phosphotyrosine
      phosphatase inhibitors described to date. Their capacity to activate IRK appears
      to derive from their phosphotyrosine phosphatase inhibitory activity. Their
      hypoglycemic action is due to a direct tissue effect.

PMID- 8308032
TI  - Binding of insect apolipophorin III to dimyristoylphosphatidylcholine vesicles.
      Evidence for a conformational change.
AB  - Apolipophorin-III (apoLp-III), a hemolymph protein of Manduca sexta, can
      reversibly associate with the surface of lipoprotein particles. In order to
      examine the lipid-associated form of apoLp-III, the present studies investigate
      the structure and properties of apoLp-III complexes with
      dimyristoylphosphatidylcholine (DMPC). Association of apoLp-III with DMPC
      vesicles results in the formation of uniform discs with an average diameter and
      width of 18.5 +/- 2.0 nm and 4.8 +/- 0.8 nm, respectively, as determined by
      electron microscopy. ApoLp-III.DMPC complexes analyzed by pore-limiting native
      gradient PAGE demonstrated that a single major species of complex was formed
      within a wide range of lipid to protein molar ratios (DMPC:apoLp-III; 13:1 to
      360:1). Flotation equilibrium experiments, conducted in an analytical
      ultracentrifuge, confirmed that only one species of apoLp-III.DMPC complex was
      formed at an initial lipid to protein molar ratio of 67:1, with an apparent
      molecular mass of 642,000. Complexes cross-linked with dimethyl suberimidate
      indicate that there are a maximum of 6 apoLp-III molecules per disc. Circular
      dichroism experiments revealed that apoLp-III becomes essentially completely
      alpha-helical on formation of apoLp-III.DMPC complexes. Compared to apoLp-III in
      the lipid-free state, apoLp-III.DMPC complexes were relatively resistant to
      denaturation by guanidine HCl, displaying denaturation transitions with midpoints
      at 2.2 and 3.7 M guanidine HCl, respectively. The fluorescence excitation and
      emission spectra of apoLp-III.DMPC complexes demonstrate a large enhancement of
      tyrosine fluorescence as compared to the lipid-free state, suggesting that a
      conformational change occurs when apoLp-III associates with a lipid surface.
      Denaturation of apoLp-III in the complex by guanidine HCl resulted in a tyrosine
      fluorescence level similar to that of lipid-free apoLp-III in the presence of
      guanidine HCl. The tyrosine-induced fluorescence of the complex was quenched with
      both Cs+ (Kq = 0.573 M-1) and KI (Kq = 0.376 M-1). The results presented in this
      study indicate that the conformation of apoLp-III is stabilized when complexed
      with phospholipids and suggest that tyrosine fluorescence provides a sensitive
      method to detect M. sexta apoLp-III interaction with lipid surfaces.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8308033
TI  - Cone arrestin identified by targeting expression of a functional family.
AB  - High acuity, color vision in humans is initiated in cones by a receptor/G-protein
      linked phototransduction cascade. G-protein-linked receptors are rapidly
      deactivated by receptor phosphorylation and the binding of a member of the
      "arrestin" family of proteins. Divergence in amino acid sequence at the carboxyl
      terminus of S-antigen (rod photoreceptor arrestin) and beta-arrestin 1 and beta
      arrestin 2 (beta-adrenergic receptors) suggests that receptor specificity may be
      coded within this region. An anchor primer strategy was utilized to screen for
      carboxyl-terminal variability with a rat pineal library, identifying three known
      arrestins plus three unknowns (C-arrestin, D-arrestin, and E-arrestin). cDNA was
      prepared by reverse transcription of mRNA from 12 rat tissues, and members of the
      arrestin family were amplified by polymerase chain reaction using the anchor
      primer and customized 3'-primers for the individual arrestins. The amplified
      arrestins were then digested by selected restriction endonucleases, producing a
      pattern of characteristic cleavage products for each arrestin isoform. The
      procedural combination of epitope domain anchor and tissue screening demonstrated
      that C-arrestin is enriched in the retina. C-arrestin was isolated from a lambda
      MAX1 human retinal cDNA library and sequenced, revealing significant identity to
      known arrestins and divergence within the 3'-region. The mRNA for C-arrestin was
      visualized by in situ hybridization, localizing in the retina with cone
      photoreceptors and in the pineal to a subpopulation of pinealocytes. A gene for
      human C-arrestin was mapped to the X chromosome, making C-arrestin a candidate
      for several inherited X-linked retinopathies. The localization of C-arrestin to
      cone photoreceptors suggests that it, like others in the arrestin family, may
      bind to phosphorylated receptors and participate in deactivation of the
      phototransduction cascade.

PMID- 8308034
TI  - Identification of the poly-L-proline-binding site on human profilin.
AB  - Profilin is a ubiquitous protein that has been implicated in the signaling
      pathway leading to cytoskeletal rearrangement in cells. An unusual property of
      profilin is its high binding affinity for poly-L-proline (PLP). This binding
      property is conserved in the profilins from diverse species with little sequence
      homology. We have monitored the binding of PLP to profilin by fluorescence and
      nuclear magnetic resonance spectroscopies. NMR spectroscopy has identified
      several residues whose amide nitrogen and amide hydrogen chemical shifts are
      significantly perturbed by binding of PLP. The affected residues are located at
      various locations throughout profilin's primary structure; however, mapping the
      location of the affected residues onto the recently determined three-dimensional
      solution structure of human profilin indicates that the effects of PLP binding
      are highly localized. Poly-L-proline binds profilin at the hydrophobic interface
      between profilin's NH2- and COOH-terminal helices and the upper face of its
      antiparallel beta-sheet. In contrast, residues located on the opposite side of
      the profilin structure are unaffected. The extent of the potential interaction
      surface of the PLP-profilin complex suggests that as few as 6 contiguous prolines
      would be sufficient for binding profilin. Examination of sequence data bases
      indicates that stretches of prolines of this length and longer occur in numerous
      regulatory proteins, suggesting that the ability of profilin to bind polyproline
      may be an important component of its signaling capabilities.

PMID- 8308035
TI  - Lipoprotein lipase. Molecular model based on the pancreatic lipase x-ray
      structure: consequences for heparin binding and catalysis.
AB  - Lipoprotein lipase and pancreatic lipase have about 30% sequence identity,
      suggesting a similar tertiary fold. Three-dimensional models of lipoprotein
      lipase were constructed, based upon two recently determined x-ray crystal
      structures of pancreatic lipase, in which the active site was in an open and
      closed conformation, respectively. These models allow us to propose a few
      hypotheses on the structural determinants of lipoprotein lipase which are
      responsible for heparin binding, dimer formation, and phospholipase activity. The
      folding of the protein assembles a number of positive charge clusters at the back
      of the molecule, opposite the active site. These clusters probably form the
      heparin binding site, as confirmed by recent site-directed mutagenesis
      experiments. The active sites of lipoprotein lipase and pancreatic lipase look
      very similar, except for the lid (a surface loop covering the catalytic serine in
      the inactive state). A different open (active) conformation of the lid in both
      enzymes may be responsible for their differing substrate specificities.
      Predictions of the nature of the lipoprotein lipase dimer remain elusive,
      although our model enabled us to propose a few possibilities.

PMID- 8308036
TI  - Overproduction of a Ca(2+)-independent protein kinase C isozyme, nPKC epsilon,
      increases the secretion of prolactin from thyrotropin-releasing hormone
      stimulated rat pituitary GH4C1 cells.
AB  - Rat pituitary GH4C1 cells express protein kinase C (PKC) transcripts for cPKC
      alpha, cPKC beta II, nPKC delta, nPKC epsilon, nPKC eta, and aPKC zeta, but not
      for cPKC gamma or nPKC theta. Of the transcripts produced, the nPKC epsilon
      isoform is the most abundant. Transfection of GH4C1 cells with an expression
      plasmid containing nPKC epsilon cDNA leads to the transient overexpression of
      cellular nPKC epsilon and confers enhanced phorbol ester binding activity.
      Transient expression of an inactive point mutant (nPKC epsilon K-->R) of nPKC
      epsilon, where Lys436 at the putative ATP-binding site is replaced with Arg, also
      confers elevated binding activity. However, only overproduction of the wild type
      in transfected cells increases the basal levels and stimulates the secretion of
      prolactin (PRL) by 12-O-tetradecanoylphorbol-13-acetate or thyrotropin-releasing
      hormone (TRH). In stable clones overexpressing nPKC epsilon,
      immunocytofluorescence and immunoblot experiments indicated that TRH causes the
      rapid translocation and down-regulation of an appreciable fraction of nPKC
      epsilon. Both the basal and TRH-stimulated levels of PRL secretion are clearly
      correlated with the expression level of nPKC epsilon but not with the TRH
      receptor densities in these clones. The dose dependence of TRH-stimulated
      secretion were similar in all cells overexpressing cPKC alpha, cPKC beta II, nPKC
      epsilon, and nPKC delta, but the enhancement of PRL secretion was specific for
      the overproduction of nPKC epsilon, no effect was found when other isozymes were
      overproduced. These findings clearly demonstrate that the expression level of
      nPKC epsilon in GH4C1 cells is rate-limiting for basal and TRH-stimulated PRL
      secretion, and they provide the first direct evidence that nPKC epsilon plays a
      key role in hormonal secretory processes.

PMID- 8308037
TI  - Mouse serum amyloid A protein (SAA5) structure and expression.
AB  - A novel member of the mouse serum amyloid A protein family, SAA5, has been
      identified as a normal apolipoprotein component of non-acute-phase high density
      lipoprotein (HDL). The structure of SAA5 was derived from a clone isolated from a
      normal Balb/c liver cDNA library. The clone predicts a pre-SAA5 molecule of 130
      residues from which an 18-residue leader peptide is cleaved. The mature molecule
      has an octapeptide insert spanning from position 70 to 77. Similar inserts are
      found in human C-SAA and, paradoxically, in acute-phase SAA molecules of a number
      of other species. There is 48% amino acid identity between apo-SAA5 and the other
      mouse SAA proteins and 57% identity between the human C-SAA and apo-SAA5. The
      SAA5 mRNA is three times larger than previously identified SAA mRNAs. Although
      SAA5 is constitutively expressed in the liver, it has a rapid albeit muted
      response to inflammatory stimuli. The increase of SAA5 mRNA is due to increased
      transcription rather than mRNA stabilization. Plasma SAA5 levels during the acute
      phase are biphasic, either because of translational control or displacement from
      HDL and rapid clearance. We propose that constitutive SAAs (SAA5) on normal HDL
      contribute to its normal physiological role, whereas the dramatically inducible
      family members (SAA1, SAA2, SAA3) equip this particle for an altered functional
      role during inflammation.

PMID- 8308038
TI  - The axonal gamma-aminobutyric acid transporter GAT-1 is sorted to the apical
      membranes of polarized epithelial cells.
AB  - Recent studies suggest that epithelial cells and neurons employ similar
      mechanisms to target proteins to the distinct subdomains of their polarized cell
      surface membranes. We have examined the sorting behavior of the neuronal gamma
      aminobutyric acid (GABA) transporter GAT-1 expressed by transfection in the
      polarized epithelial Madin-Darby canine kidney (MDCK) cell line. We find that the
      GABA transporters endogenously expressed by polarized hippocampal neurons in
      culture are restricted to axonal plasma membranes. In transfected MDCK cells, the
      GABA transporter is found to be localized primarily to the apical cell surface
      when examined by immunocytochemistry, cell surface biotinylation, and transport
      assay. MDCK cells exposed to hyperosmotic stress express a close relative of GAT
      1, the betaine transporter (BGT-1). We find that BGT-1 expressed by transfection
      in MDCK cells accumulates predominantly at the basolateral cell surface. These
      observations suggest that the sorting information required for axonal targeting
      may be similar to that which mediates apical localization in epithelia.
      Furthermore, it would appear that despite their high degree of homology, the BGT
      1 and GAT-1 transporters manifest sorting signals which specify their targeting
      to distinct cell surface domains.

PMID- 8308039
TI  - Identification of a domain of Escherichia coli primase required for functional
      interaction with the DnaB helicase at the replication fork.
AB  - Primase plays a key role in governing the sequence of events required on the
      lagging strand during a cycle of Okazaki fragment synthesis. To begin to probe
      the protein-protein interactions necessary for primase function at the
      replication fork, we have used limited trypsinolysis to separate primase into two
      functional domains, an N-terminal domain of 49 kDa (p49) and a carboxyl-terminal
      domain of 16 kDa (p16). p49 retained primase activity in replication assays that
      utilized bacteriophage M13 DNA carrying the bacteriophage G4 origin of DNA
      replication as the template, but was inactive during general priming or the
      conversion of phi X174 single-stranded circular (ss(c))-DNA to the replicative
      form (RF) and could not support lagging-strand DNA synthesis at replication forks
      reconstituted with the phi X-type primosomal proteins and the DNA polymerase III
      holoenzyme. On the other hand, p16 inhibited those replication reactions that
      included the replication fork helicase, DnaB (general priming, phi X174 ss(c)-
      >RF, and at the replication fork), but had no effect on those that did not
      (M13Gori ss(c)-->RF). These results demonstrate that p49 defines a domain of
      primase required for catalytic activity, that p16 defines a domain of primase
      required for functional interaction with DnaB, and that it is a protein-protein
      interaction with DnaB that attracts primase to the replication fork.

PMID- 8308040
TI  - Crystals of a hammerhead ribozyme.

PMID- 8308041
TI  - Effects of porous coating, with and without collar support, on early relative
      motion for a cementless hip prosthesis.
AB  - In theory, porous or rough coatings could be used to reduce early post-operative
      relative motion about cementless hip prostheses. To investigate this theory, we
      used detailed, non-linear finite element analysis to compare early relative
      motion about a well-fit Anatomical Medullary Locking (AML) prosthesis for
      different amounts of porous coating (full, proximal 2/3, and no coating), both
      with and without collar support. Details of the model included quantitative
      computed tomography-derived (QCT-derived) geometric and material properties for
      the bone, and a no-tension interface condition at all bone-prosthesis interfaces,
      with Coulomb friction (mu = 1.73) over coated surfaces and zero friction
      elsewhere. Predicted values of relative motion for this well-fit device were in
      the range of approximately 1-550 microns. The distribution of relative motion was
      relatively insensitive to the amount of porous coating but was sensitive to
      collar support, while the magnitude of relative motion was sensitive to the
      porous coating and collar support. In addition, a reduction in the porous coating
      caused larger increases in relative motion when there was no collar support,
      indicating an interaction between the effects of porous coating and collar
      support. For example, distal twist increased (full vs 2/3 partial coating) by 38%
      with collar support and by 58% without collar support. These data suggest that
      porous coating, or other surface treatments which result in a high coefficient of
      friction at the bone-prosthesis interface, may well be used to control the
      magnitude of early relative motion, particularly when there is no collar support.

PMID- 8308042
TI  - Stress relaxation function of bone and bone collagen.
AB  - Relaxation Young's and shear moduli of bovine bone and bone collagen were
      investigated. It was found that each relaxation process observed had two stages,
      which were referred to as process I and process II in order of time. Process II
      was described by a simple exponential decay while process I was not. The
      Kohlrausch-Williams-Watts (KWW) function, psi(t) = exp[-(t/tau 1)B] (0 < B < 1),
      was found to be suitable to describe process I. The normalized relaxation
      modulus, M(r)(t), was expressed by the combination of the simple exponential type
      relaxation function and the KWW function M(r)(t) = A1exp[-(t/tau 1)B]+A2exp[
      (t/tau 2)] (0 < B < or = 1). On the basis of this equation, the relaxation
      mechanism in bone and bone collagen was identified. According to the model
      proposed for the KWW relaxation function, the stress relaxation process in bone
      was considered to be governed by viscoelastic properties of matrix collagen
      fiber. The model for the KWW relaxation function requires the disordered glassy
      structure of collagen fiber, which is consistent with the results of the
      structural investigations.

PMID- 8308043
TI  - Spatial and temporal variations of wall shear stress within an end-to-side
      arterial anastomosis model.
AB  - Wall shear stress has been strongly implicated in the initiation of fibrous
      intimal hyperplasia that leads to arterial bypass graft failure. In this study,
      the photochromic tracer technique was used to determine the instantaneous value
      of the wall shear stress in order to provide a detailed description of its
      spatial and temporal variations within a 45 degrees end-to-side anastomosis
      model. At the heel and on the bed across from the heel, the shear stress was
      close to zero throughout the sinusoidal flow cycle. Flow separation was produced
      just beyond the toe where the peak phase-averaged shear stress was 6 dyn cm-2,
      whilst on the bed across from the toe it was 27 dyn cm-2. The stagnation point
      was seen to fluctuate quite sharply on the bed over a distance of about one tube
      radius upstream from the site across from the toe. This led to large spatial
      gradients of the wall shear stress with a peak value of 580 dyn cm-3. In
      addition, the sudden motion of the stagnation point around peak flow produced
      sharp temporal gradients of the wall shear stress with a peak absolute value of
      3400 dyn cm-2 s-1. When compared to the sites where intimal hyperplasia tends to
      occur, a strong correlation is seen with low wall shear stress at the heel and
      toe, and with the sharp temporal variations of the magnitude and spatial gradient
      of the wall shear stress on the bed across from the junction.

PMID- 8308044
TI  - Carpal bone kinematics and ligament lengthening studied for the full range of
      joint movement.
AB  - Present data on carpal kinematics and carpal ligament behaviour are limited to
      flexion and deviation movements of the hand. These motions do not represent all
      the wrist-joint motions which are important for the activities of daily living.
      The goal of this project was to obtain insight into carpal kinematics and carpal
      ligament behaviour during motions of the hand covering the full range of motion
      of the wrist joint. The carpals and the ligaments of four wrist-joint specimens
      were provided with radiopaque markers. These joints were subjected to
      Rontgenstereophotogrammetric experimentation in a large number of hand positions
      to determine carpal positions and ligament lengths. The movements of the carpal
      bones were described by means of finite helical axes (FHA). It was found that the
      movements of the carpals in the distal row closely resemble those of the hand.
      Conversely, the motions of the carpals of the proximal row appeared not to be
      directly proportional to the hand motions and exhibited clear out-of-plane
      movements. Furthermore, it could be shown that movements of the hand into the
      ulnodorsal quadrant of the full range of hand motion corresponds to larger
      helical rotations and translations for most of the carpals than when the hand was
      moved into any other quadrant. The maximal ligament length changes determined did
      not exceed the length changes reported for pure flexion and pure deviation
      movements of the hand.

PMID- 8308045
TI  - Finger joint force minimization in pianists using optimization techniques.
AB  - A numerical optimization procedure was used to determine finger positions that
      minimize and maximize finger tendon and joint force objective functions during
      piano play. A biomechanical finger model for sagittal plane motion, based on
      finger anatomy, was used to investigate finger tendon tensions and joint reaction
      forces for finger positions used in playing the piano. For commonly used piano
      key strike positions, flexor and intrinsic muscle tendon tensions ranged from 0.7
      to 3.2 times the fingertip key strike force, while resultant inter-joint
      compressive forces ranged from 2 to 7 times the magnitude of the fingertip force.
      In general, use of a curved finger position, with a large metacarpophalangeal
      joint flexion angle and a small proximal interphalangeal joint flexion angle,
      reduces flexor tendon tension and resultant finger joint force.

PMID- 8308046
TI  - Storage and utilization of elastic strain energy during jumping.
AB  - Based upon the optimal control solutions to a maximum-height countermovement jump
      (CMJ) and a maximum-height squat jump (SJ), this paper provides a quantitative
      description of how tendons and the elastic elements of muscle store and deliver
      energy during vertical jumping. After confirming the ability of the model to
      replicate the major features of each jump (i.e. muscle activation patterns, body
      segmental motions, ground reaction forces, jump height, and total ground contact
      time), the time histories of the forces and shortening velocities of all the
      musculotendon actuators in the model were used to calculate the work done on the
      skeleton by tendons as well as the series-elastic elements, the parallel-elastic
      elements, and the contractile elements of muscle. We found that all the elastic
      tissues delivered nearly the same amount of energy to the skeleton during a CMJ
      and an SJ. The reason is twofold: first, nearly as much elastic strain energy was
      stored during the SJ as the CMJ; second, more stored elastic strain energy was
      lost as heat during the CMJ. There was also a difference in the way energy was
      stored during each jump. During the CMJ, strain energy stored in the elastic
      tissues came primarily from the gravitational potential energy of the skeleton as
      the more proximal extensor muscles were stretched during the downward phase of
      the jump. During the SJ, on the other hand, energy stored in the elastic tissues
      came primarily from the contractile elements as they did work to stretch the
      tendons and the series-elastic elements of the muscles. Increasing tendon
      compliance in the model led to an increase in elastic energy storage and
      utilization, but it also decreased the amount of energy delivered by the
      contractile elements to the skeleton. Jump height therefore remained almost the
      same for both jumps. These results suggest that elastic energy storage and
      utilization enhance jumping efficiency much more than overall jumping
      performance.

PMID- 8308047
TI  - An EMG-assisted model of loads on the lumbar spine during asymmetric trunk
      extensions.
AB  - An EMG-assisted, low-back, lifting model is presented which simulates spinal
      loading as a function of dynamic, asymmetric, lifting exertions. The purpose of
      this study has been to develop a model which overcomes the limitations of
      previous models including static or isokinetic mechanics, inaccurate predictions
      of muscle coactivity, static interpretation of myoelectric activity, and
      physiologically unrealistic or variable muscle force per unit area. The present
      model predicts individual muscle forces from processed EMG data, normalized as a
      function of trunk angle and asymmetry, and modified to account for muscle length
      and velocity artifacts. The normalized EMGs are combined with muscle cross
      sectional area and intrinsic strength capacity as determined on a per subject
      basis, to represent tensile force amplitudes. Dynamic internal and external force
      vectors are employed to predict trunk moments, spinal compression, lateral and
      anterior shear forces. Data from 20 subjects performing a total of 2160 exertions
      showed good agreement between predicted and measured values under all trunk
      angle, asymmetry, velocity, and acceleration conditions. The design represents a
      significant step toward accurate, fully dynamic modeling of the low-back in
      multiple dimensions. The benefits of such a model are the insights provided into
      the effects of motion induced, muscle co-activity on spinal loading in multiple
      dimensions.

PMID- 8308048
TI  - Reflection coefficients in pulsatile flow through converging junctions and the
      pressure distribution in a simple loop.
AB  - Analytical expressions for the reflection coefficients in pulsatile flow through
      converging junctions are derived by two independent methods and are used to study
      the effects of wave reflections on the pressure distribution in a simple vascular
      loop. A simulated physiological situation is used as an example in which the loop
      is formed by the combination of a bypass and a bypassed vessel, the relative
      diameter of the latter being varied in order to simulate a narrowing. The results
      demonstrate how, in the case of a converging junction, the effects of wave
      reflections on the pressure distribution in one vessel depend on conditions
      within the vessel itself as well as in the other. The new reflection coefficients
      take into account this interdependence of flow in the two vessels forming a
      converging junction, and are shown to be consistent with reflection coefficients
      commonly used in diverging junctions.

PMID- 8308049
TI  - Comparative assessment of two algorithms for calibrating stereophotogrammetric
      systems.
AB  - In this paper, a comparison is carried out between two photogrammetric algorithms
      aimed at camera calibration and three-dimensional target point reconstruction by
      'absolute' distributions of control points; the first is Marzan and Karara's DLT,
      the second is CESNO, by the author, an algorithm quite close to Hatze's modified
      DLT (MDLT). The comparative assessment is especially aimed at testing the
      capability of the two methods to produce good results when calibration data are
      to be extrapolated beyond the space spanned by the control distribution. The
      assessment was carried out not by a real stereophotogrammetric system, but by the
      computer simulation of a two-camera set-up. Various combinations of internal
      camera parameters, such as the scaled principal distances, were tried out. As for
      the magnitude of the simulated non-linear lens distortion, three configurations
      were used which produced 'low', 'medium' and 'strong' distortion. The influence
      of decreasing the number of control (calibration) points on the accuracy
      performance of the two algorithms was also investigated. The results show the
      superiority of CESNO, especially with medium or strong lens distortion, or when
      the two camera principal distances sensibly differ.

PMID- 8308050
TI  - Displacement analysis of the temporomandibular condyle from magnetic resonance
      images.
AB  - A technique was developed to investigate the condylar displacement of the human
      temporomandibular joint. Condylar displacement was analyzed from magnetic
      resonance images of the joint. Fourteen static images were obtained during
      incremental jaw closure. Landmarks were identified on the magnetic resonance
      images and reference points were digitized. The condylar displacement was
      calculated based on an optimization algorithm. The technique was proven to be
      reproducible based on two feasibility tests. The results provided quantitative
      descriptions of the condylar displacement as a function of a prescribed jaw
      movement. The displacement was characterized by a translation of an anatomical
      point on the condyle and a rotation of the mandible. The condylar displacement
      was 6 mm at a mouth opening of 17 mm. Maximum rotation of the mandible was 12.3
      degrees C. The motion of the condyle produced by the mechanical guidance system
      used in this study may be characterized as a small forward translation at the
      beginning of jaw opening, followed by a combination of translation and rotation.

PMID- 8308051
TI  - Telemetry system to record force and EMG from cat ankle extensor and tibialis
      anterior muscles.
AB  - The purpose of this technical note is to present the design of an eight-channel
      telemetry system of dimensions and weight small enough to record muscular forces
      and EMGs simultaneously from gastrocnemius, soleus, plantaris and tibialis
      anterior muscles of a freely moving cat. All schematics for constructing the
      telemetry device are shown in detail. Using this system, we were successful in
      measuring force and EMG data of all four instrumented muscles in freely moving
      animals. The telemetry system presented here has the advantage over a
      conventional cable system that recordings may be obtained at any time in the
      freely moving animal without interference by an experimenter.

PMID- 8308052
TI  - Determining the movements of the skeleton using well-configured markers.
AB  - The problem of determining skeletal movements in three dimensions by using a
      number of landmarks is treated. We present a method that determines the motion of
      a rigid body by using the positions of the landmarks in least-squares sense. The
      method uses the singular value decomposition of a matrix derived from the
      positions of the landmarks. We show how one can use this method to express
      movement of skeleton segments relative to each other. As many others have pointed
      out, the movement can be very ill determined if the landmarks are badly
      configured. We present a condition number for the problem with good geometrical
      properties. The condition number depends on the configuration of the landmarks
      and indicates how to distribute the landmarks in a suitable way.

PMID- 8308053
TI  - Pressure distribution on mattresses.
AB  - Measurements of pressure distribution are usually performed on a hard base, such
      as those in gait analysis or tire research; measurements on soft surfaces are
      avoided because of technical problems. A sensor mat was developed which consists
      of 512 pressure sensors, glued to arbitrary locations of a fabric. The mat can be
      bent to spherical and saddle shapes so that it can be utilised on soft and
      flexible surfaces like chairs and beds. Performance of eight hospital mattresses
      concerning decubitus prophylactics and support in supine and side position was
      studied in four subjects representing extreme body build. It was found that one
      particular mattress served well for three subjects, whereas no mattress was
      suitable for the high and heavy type. It was concluded that measurement of
      pressure distribution is a valuable tool for designing and selecting.

PMID- 8308054
TI  - Intracellular relationship between actin and alpha-actinin in a whole corneal
      epithelial tissue.
AB  - Alpha-actinin is an actin crosslinking protein that may be one of the proteins
      involved in the attachment of the actin cytoskeletal framework to the plasma
      membrane. We investigated the distribution of alpha-actinin in whole-mount
      embryonic chick corneal epithelia using confocal laser scanning analysis. The
      intracellular alpha-actinin distribution was compared with F-actin using
      phalloidin, or total actin using an anti-actin antibody. Corneal epithelial
      tissues were isolated with or without the basal lamina (+ or -BL), and fixed
      immediately. In addition, epithelia isolated -BL were cultured for 2 hours with
      either control medium, laminin-supplemented medium or laminin and cytochalasin D
      (CD)-containing medium. The single- and double-labeled epithelia showed that
      alpha-actinin delineated the cell borders and microvilli of the periderm cells in
      the most apical optical sections of control and laminin-treated epithelia. At the
      optical plane through the basal cell nuclei, the alpha-actinin was distributed
      diffusely throughout the cytoplasm, whereas the actin was sparse, only associated
      with the lateral cell membranes. Epithelia (-BL) cultured in control medium had
      cytoplasmic protrusions or blebs on the basal cell surface. The blebs contained
      both actin and alpha-actinin. In epithelial cultured with laminin, the basal cell
      surface was flat. The actin cortical mat became reorganized within two hours.
      Actin and alpha-actinin were colocalized in the re-formed basal cytoskeletal
      network. In cells cultured with cytochalasin D (CD) and laminin the actin
      cortical mat was not reorganized. Actin networks from both cell layers were
      eliminated and replaced by aggregates scattered throughout the cytoplasm. The
      alpha-actinin remained diffusely distributed in the cytoplasm and failed to
      colocalize with the actin aggregates. The alpha-actinin appeared closer to the
      basal cell membrane than the actin in cross-sectional views of the tissue.
      Results from these double-labeling experiments confirmed the intimate association
      of alpha-actinin and actin in the laminin-stimulated actin cortical mat
      reorganization. This study is the first to demonstrate that CD-aggregated F-actin
      does not capture the alpha-actinin. The alpha-actinin appeared to remain diffuse
      throughout the cytoplasm and separate from F-actinin; however, there was some
      overlap with G-actin.

PMID- 8308055
TI  - A centrosome-associated antibody from Drosophila melanogaster reveals a new
      microtubule-dependent structure in the equatorial zone of Parascaris univalens
      embryos.
AB  - The distribution of antigens to two antibodies (Bx63 and Rb188) that associate to
      Drosophila melanogaster centrosomes has been investigated in the nematode
      Parascaris. By western blot analysis both antibodies identify in Parascaris
      polypeptides of the same molecular mass as in Drosophila (Rb188 a 185 kDa antigen
      and Bx63 185 kDa and 66 kDa antigens). By immunocytochemistry we show that the
      centrosomes of Parascaris contain the 185 kDa antigen recognized by polyclonal
      Rb188 and monoclonal Bx63 antibodies. In addition, Bx63 reveals cytoplasmic
      midzone structures, not found in Drosophila, that display a cell cycle-dependent
      organization in embryos. These structures, which most probably contain the 66 kDa
      antigen revealed by Bx63, appear at the onset of anaphase as fibrillar-like
      structures that during anaphase form a ring-like structure encircling the
      equatorial plane of the blastomere. Before furrowing, the antigen participates in
      the formation of the midbody and associates with convergent polar microtubules.
      After blastomere division, Bx63 signal persists as a single body between the
      daughter cells. The analysis of chilled and nocodazole-treated embryos suggests
      that the localization of the midzone Bx63 antigen is dependent on non-kinetochore
      microtubules. Inhibition of furrowing by cytochalasin B shows that the antigen
      persists after the disassembly of microfilaments. Cytological observations of
      contractile ring and Bx63 ring assembly indicate that both structures do not
      simultaneously colocalize at the equatorial zone. The data suggest a spindle
      dependent distribution of the Bx63 antigen during cytokinesis. We discuss the
      participation of this antigen in the organization of the midbody before
      furrowing, and consider the possible relevance of the midbody with respect to
      cell to cell communication during early development in nematodes.

PMID- 8308056
TI  - Regulated and constitutive secretion of distinct molecular forms of
      acetylcholinesterase from PC12 cells.
AB  - PC12 cells secrete the enzyme acetylcholinesterase (AChE) while at rest, and
      increase the overall rate of this secretion 2-fold upon depolarization. This
      behavior is different from the release of other markers by the constitutive or
      regulated secretory pathways in PC12 cells. Both the resting and stimulated
      release of AChE are unchanged after treatment with a membrane-impermeable
      esterase inhibitor, demonstrating that it represents true secretion and not
      shedding from the cell surface. The stimulation release of AChE is Ca(2+)
      dependent, while the unstimulated release is not. Analysis of the molecular forms
      of AChE secreted by PC12 cells indicates that the release of AChE actually
      involves two concurrent but independent secretory processes, and that the G4 form
      of the enzyme is secreted constitutively, while both the G2 and G4 forms are
      secreted in a regulated manner, presumably from regulated secretory vesicles.
      Compared with other regulated secretory proteins, a much smaller fraction of
      cellular AChE is secreted, and the intracellular localization of this enzyme
      differs from that of other regulated secretory proteins. The demonstration that a
      cell line that exhibits regulated secretion of acetylcholine (ACh) is also
      capable of regulated secretion of AChE provides additional evidence for the
      existence of multiple regulated secretory pathways within a single cell.
      Moreover, there appears to be a selective packaging of different molecular forms
      of AChE into the regulated versus the constitutive secretory pathway. Both the
      specificity of sorting of AChE and the regulation of its secretion suggest that
      AChE may play a more dynamic role in synaptic function than has been recognized
      previously.

PMID- 8308057
TI  - The analysis of 40 kDa nuclear protein, p40, in interphase cells and mitotic
      cells.
AB  - We previously reported that the monoclonal antibody M108 recognized a 40 kDa
      protein both in the nucleus and the cytoplasm. This nuclear 40 kDa antigen was
      located in the nuclear envelope in interphase cells and in the perichromosomal
      region during mitosis. Now, we have analyzed this nuclear 40 kDa protein (p40)
      further, through morphological and biochemical approaches. At the beginning of
      mitosis, the perinuclear p40 detached from the nuclear envelope and moved to
      surround the condensing chromatin, while in the late stage of mitosis, the
      perichromosomal p40 moved back to the reassembled nuclear envelope. Most of the
      perichromosomal p40 on the metaphase chromosome was solubilized only by DNase I
      treatment, not by either high salt or detergent treatment. On the other hand, the
      perinuclear p40 was not solubilized by DNase1 alone, or high salt detergent
      alone. Sequential treatments with DNase I and high salt detergent were required
      to extract p40 in interphase nuclei. These results suggest that p40 was
      associated both with the nuclear envelope and chromatin DNA in interphase nuclei,
      while it bound only to chromatin DNA in mitosis.

PMID- 8308058
TI  - Titin aggregates associated with intermediate filaments align along stress fiber
      like structures during human skeletal muscle cell differentiation.
AB  - Differentiating human skeletal muscle cell cultures were used to study the
      association of titin with other sarcomeric and cytoskeletal proteins during
      myofibrillogenesis. Several developmental stages of these cultures were double
      stained with antibodies to titin in combination with antibodies to alpha-actin,
      alpha-actinin, myosin heavy chain (MHC), nebulin, desmin, and beta-tubulin. The
      first indications of titin expression were found in postmitotic mononuclear
      myoblasts where it is located in a random, punctate fashion. At the light
      microscope level no evidence was found for an association of these titin spots
      with any of the other proteins studied, with the exception of MHC, which
      colocalized with titin in a small minority of the titin expressing cells.
      Subsequently the titin spots were found to be linked to longitudinally oriented
      stress fiber-like structures (SFLS), containing alpha-actinin and sarcomeric
      alpha-actin, but not MHC, nebulin or desmin. Upon further maturation titin
      antibodies seemed to stain SFLS in a rather homogeneous fashion together with
      MHC, alpha-actin and alpha-actinin. Thereafter a more periodic localization of
      titin, MHC, alpha-actin and alpha-actinin on SFLS became obvious. From these
      structures myofibrils developed as a result of further differentiation. Initially
      only short stretches with a striated titin, MHC, F-actin and alpha-actinin
      organization were found. Nebulin was integrated in these young myofibrils at a
      later developmental stage. Desmin was not found to be incorporated in these
      myofibrils until complete alignment of the sarcomeres in mature myotubes had
      occurred. At the ultrastructural level titin antibodies recognized aggregates
      that were associated with intermediate filaments (IF) in postmitotic mononuclear
      myoblasts. At a later maturational stage, prior to the development of cross
      striated myofibrils, the IF-associated titin aggregates were found in close
      association with subsarcolemmally located SFLS. We conclude that IF and SFLS play
      an important role in the very early stages of in vitro human myofibrillogenesis.
      On the basis of our results we assume that titin aggregates are targeted to SFLS
      through IF. The association of titin with SFLS might be crucial for the unwinding
      of titin necessary for the assembly of sarcomeres and the first association of
      titin with other sarcomeric proteins.

PMID- 8308059
TI  - Localisation of granulocyte macrophage colony-stimulating factor in human long
      term bone marrow cultures. Biological and immunocytochemical characterisation.
AB  - The distribution of granulocyte macrophage colony-stimulating factor (GM-CSF) in
      human long-term bone marrow cultures (HLTBMC) was examined using two monoclonal
      antibodies raised using purified recombinant GM-CSF and a third commercially
      available GM-CSF antibody. The antibodies were able to bind to purified
      recombinant GM-CSF and showed inhibition of GM-CFC colonies in the presence of
      both recombinant and native protein. All antibodies displayed similar patterns of
      distribution in both permeabilised and non-permeabilised stromal cell
      preparations. Fibroblasts were labelled at their periphery in early cultures and
      both endothelial cells and fibroblasts showed cytoplasmic labelling with anti-GM
      CSF. The fact that GM-CSF appears to be sequestered by cells of the bone marrow
      stroma raises the possibility that it is synthesized by these cells and may
      regulate activity of the progenitor cells in the haemopoietic foci. In contrast,
      early progenitor cells within the foci did not stain with any of the anti-GM-CSF
      antibodies. Adipocytes, which differentiate from fibroblasts in these cultures,
      showed a diffuse staining pattern. Two types of macrophage staining were observed
      in the non-permeabilised cells; those exhibiting only autofluorescence and those
      that bound the antibody. Intracellular staining was apparent in a small sub
      population. Generally, the staining persisted up to eight weeks of culture and
      thereafter declined, becoming virtually undetectable after 12 weeks. This
      correlates with the pattern of GM-CFC production in long-term bone marrow
      cultures.

PMID- 8308060
TI  - Differential expression of the human mucin genes MUC1 to MUC5 in relation to
      growth and differentiation of different mucus-secreting HT-29 cell
      subpopulations.
AB  - Mucin expression was analysed, in relation to cell growth, in parental HT-29
      cells and in two populations of mucus-secreting HT-29 cells selected by
      adaptation to methotrexate (HT29-MTX) or 5-fluorouracil (HT29-FU). These two
      populations express mature mucins that differ in their immunoreactivity to
      antibodies against gastric (HT29-MTX) or colonic mucins (HT29-FU). In the
      parental population, at late confluency, only very few cells produce mucins or
      the MUC1 glycoprotein, this being consistent with the low level of expression of
      the mRNAs corresponding to the MUC1 to MUC5C mucin genes. In the HT29-MTX and
      HT29-FU populations, the appearance of mucus droplets, as shown by histochemistry
      and immunofluorescence, starts a few days after confluency, progressively
      involving a greater proportion of cells and reaching a steady state at late
      confluency. The MUC1 glycoprotein appears earlier, already being detectable in
      preconfluent cells. Its distribution is restricted to the apical surface of the
      cells and is distinct from that of the mucus droplets. In both populations the
      growth-related levels of MUC1 mRNA are concordant with the apparent levels of
      expression of the MUC1 glycoprotein. The levels of MUC2, MUC3, MUC4 and MUC5C
      mRNAs differ from one population to another and, within each population,
      according to the stage of the culture. The highest levels of MUC2 and MUC4 mRNAs
      are found in the HT29-FU cells, whereas the highest levels of MUC3 and MUC5C are
      found in the HT29-MTX cells, suggesting that the differences observed in the
      mature mucins expressed by either population may be related to which MUC genes
      are expressed. In both populations significant or even high levels of MUC mRNAs
      are already present in early cultures, i.e. at a stage when the mature mucins are
      not yet detectable, suggesting that mucin maturation is a later event.

PMID- 8308061
TI  - Antisense RNA inactivation of gp138 gene expression results in repression of
      sexual cell fusion in Dictyostelium discoideum.
AB  - A glycoprotein, gp138, is implicated in the sexual cell fusion of Dictyostelium
      discoideum. We previously cloned and sequenced the two genes encoding the gp138
      protein, GP138A and GP138B (Fang et al. (1993) Dev. Biol. 156, 201-208). Here, we
      have constructed a vector producing antisense RNA for the gp138 genes and have
      transformed the vector into Dictyostelium cells. The transformed cells showed a
      reduction in the amounts of gp138 mRNA and protein and their sexual cell fusion
      activity was considerably repressed.

PMID- 8308062
TI  - The small GTP-binding protein rab6p is redistributed in the cytosol by brefeldin
      A.
AB  - Rab6 protein belongs to the Sec4/Ypt/rab subfamily of small GTP-binding proteins
      involved in intracellular membrane trafficking in yeast and mammalian cells. Its
      localization both in medial and trans-Golgi network prompted us to study the
      effects of brefeldin A (BFA) on rab6p redistribution. By two techniques, indirect
      immunofluorescence and cell fractionation, we investigated the fate of rab6p and
      compared it to other Golgi or trans-Golgi network markers in BHK-21 and NIH-3T3
      cells. BFA, at 5 micrograms/ml, induced redistribution of rab6p according to a
      biphasic process: during the first 10-15 minutes, tubulo-vesicular structures-
      colabelled with a bona fide medial Golgi marker called CTR 433--were observed;
      these structures were then replaced by punctate diffuse staining, which was
      stable for up to 3 hours. The 110 kDa peripheral membrane protein beta-COP was
      released much more rapidly from the Golgi membranes, whereas the trans-Golgi
      network marker TGN 38 relocated to the microtubule organizing center. The
      kinetics of reversion of BFA action on these antigens was also followed by
      immunofluorescence. Consistent with these results, rab6 antigen, originally found
      as 40% in the cytosolic versus 60% in the particulate (P 150,000 g) fraction,
      became almost entirely cytosolic; moreover, it partitioned in the aqueous phase
      of Triton X-114 whereas the membrane fraction was detergent-soluble. Rab6p did
      not become part of the coatomers after its BFA-induced release from Golgi
      structures. Three requirements seemed to be necessary for such a release:
      integrity of the microtubules, presence of energy, and a hypothetical trimeric G
      protein, as revealed by the respective roles of nocodazole, ATP depletion, and
      sensitivity to aluminium fluoride. Finally, we have shown that BFA does not
      prevent attachment of newly synthesized rab6p to membranes.

PMID- 8308063
TI  - Rab6 is associated with a compartment that transports rhodopsin from the trans
      Golgi to the site of rod outer segment disk formation in frog retinal
      photoreceptors.
AB  - The biogenesis of light sensitive membranes in retinal rod photoreceptors
      involves polarized sorting and targeting of newly synthesized rhodopsin to a
      specialized domain, the rod outer segment (ROS). We have isolated and
      characterized the population of post-Golgi membranes that mediate intracellular
      transport of rhodopsin. In the present study we have examined the association of
      small (20-25 kDa) GTP-binding (G) proteins with these membranes. We found that
      one of the small G proteins, rab6, behaves like an integral membrane protein of
      the post-Golgi vesicles, although approximately 30% of rab6 is soluble. The
      distribution of the membrane-associated and the soluble forms is highly
      polarized. By confocal and EM immunocytochemistry it can be seen that most of
      rab6 is associated with the photoreceptor trans-Golgi cisternae, trans-Golgi
      network (TGN) and post-Golgi vesicles. The photoreceptor axon and synaptic
      terminal are unlabeled, but dendrites of deeper retinal layers are labeled. The
      distribution of rab6 across sucrose density gradient fractions parallels the
      distribution of sialyltransferase (a TGN marker) activity. About 9% of membrane
      bound rab6 is associated, however, with the rhodopsin-bearing sialyltransferase
      free post-Golgi vesicles, which represent a very small fraction (< 1%) of the
      total retinal membranes. Rab6 is absent from the mature ROS disk membranes but it
      is present at the sites of new ROS disk formation and in the ROS cytoplasm. This
      suggests that rab6 becomes soluble upon disk membrane formation. Therefore, rab6
      may function not only as a component of the sorting machinery of photoreceptors
      that delivers rhodopsin to its appropriate subcellular domain but may also
      participate in some aspects of ROS disk morphogenesis.

PMID- 8308064
TI  - Immunoisolation of Kex2p-containing organelles from yeast demonstrates
      colocalisation of three processing proteinases to a single Golgi compartment.
AB  - One of the Golgi compartments of Saccharomyces cerevisiae is defined by the
      presence of a specific endoproteinase, Kex2p, which cleaves precursor
      polypeptides at pairs of basic residues. We have used antibodies directed against
      the cytoplasmically disposed C-terminal domain of Kex2p to develop an immuno
      affinity procedure for the isolation of Kex2p-containing organelles. The method
      gives a high yield of sealed organelles that are essentially free of
      contamination from other secretory pathway organelles while being significantly
      enriched for two other late Golgi enzymes, dipeptidylaminopeptidase A and the
      Kex1 carboxypeptidase. Our findings provide clear evidence for a single yeast
      Golgi compartment containing all three late-processing enzymes, which is likely
      to be the functional equivalent in yeast of the mammalian trans-Golgi network.

PMID- 8308065
TI  - Involvement of Ypt7p, a small GTPase, in traffic from late endosome to the
      vacuole in yeast.
AB  - The YPT7 gene encodes the Saccharomyces cerevisiae homolog of mammalian rab7
      protein. Data obtained from studies on a delta ypt7 mutant suggested that Ypt7p
      is involved in the endocytic pathway in yeast (Wichmann et al., Cell 71, 1131
      1142, 1992). We report here that endocytosed pheromone alpha-factor accumulates
      in late endosomes in delta ypt7 cells, indicating that Ypt7p is involved in the
      regulation of transport steps from late endosomes to the vacuole. We also show
      that alpha-factor can be degraded in a PEP4-dependent manner in a
      prevacuolar/endosomal compartment in delta ypt7 cells, providing independent
      evidence that the pathways of vacuole biogenesis and endocytosis in yeast may
      intersect in the endosomal membrane system.

PMID- 8308066
TI  - The MHC class II-associated invariant chain contains two endosomal targeting
      signals within its cytoplasmic tail.
AB  - The oligomeric complex formed by major histocompatibility complex (MHC) class II
      alpha and beta chains and invariant chain (Ii) assembles in the endoplasmic
      reticulum and is then transported via the Golgi complex to compartments of the
      endocytic pathway. When Ii alone is expressed in CV1 cells it is sorted to
      endosomes. The Ii cytoplasmic tail has been found to be essential for targeting
      to these compartments. In order to characterize further the signals responsible
      for endosomal targeting, we have deleted various segments of the cytoplasmic
      tail. The Ii mutants were transiently expressed and the cellular location of the
      proteins was analyzed biochemically and morphologically. The cytoplasmic tail of
      Ii was found to contain two endosomal targeting sequences within its cytoplasmic
      tail; one targeting sequence was present within amino acid residues 12-29 and
      deletion of this segment revealed the presence of a second endosomal targeting
      sequence, located within the first 11 amino acid residues. The presence of a
      leucine-isoleucine pair at positions 7 and 8 within this sequence was found to be
      essential for endosomal targeting. In addition, the presence of this L-I motif
      lead to accumulation of Ii molecules in large endosomal vacuoles containing
      lysosomal marker proteins. Both wild type Ii and Ii mutant molecules containing
      only one endosomal targeting sequence were rapidly internalized from the plasma
      membrane. When the Ii cytoplasmic tail was fused to the membrane-spanning region
      of neuraminidase, a resident plasma membrane protein, the resulting chimera (INA)
      was found in endocytic compartments containing lysosomal marker proteins. Thus
      the cytoplasmic tail of Ii is sufficient for targeting to the endocytic/lysosomal
      pathway.

PMID- 8308067
TI  - Ultrastructure of the endocytotic pathway in glutaraldehyde-fixed and high
      pressure frozen/freeze-substituted protoplasts of white spruce (Picea glauca).
AB  - An ultrastructural study of endocytosis has been made for the first time in
      protoplasts of a gymnosperm, white spruce (Picea glauca), fixed by high-pressure
      freezing and freeze substitution. Protoplasts derived from the WS1 line of
      suspension-cultured embryogenic white spruce were labelled with cationized
      ferritin, a non-specific marker of the plasma membrane. The timing of cationized
      ferritin uptake and its subcellular distribution were determined by fixing
      protoplasts at various intervals after labelling. To address concerns about using
      chemical fixation to study the membrane-bound transport of cationized ferritin,
      protoplasts were fixed both by conventional glutaraldehyde fixation and by rapid
      freezing in a Balzers high-pressure freezing apparatus (followed by freeze
      substitution). Cationized ferritin appeared rapidly in coated pits and coated
      vesicles after labelling. Later it was present in uncoated vesicles, and in Golgi
      bodies, trans-Golgi membranes and partially coated reticula, then subsequently in
      multivesicular bodies, which may ultimately fuse with and deliver their contents
      to lytic vacuoles. The results show that the time course and pathway of
      cationized ferritin uptake in the gymnosperm white spruce is very similar to the
      time course and pathway elucidated for cationized ferritin uptake in the
      angiosperm soybean. High-pressure freezing yielded much better preservation of
      intracellular membranes and organelles, although plasma membranes appeared
      ruffled. Protoplasts fixed by both methods possessed numerous smooth vesicles in
      the cortex and smooth invaginations of the plasma membrane. These became labelled
      with cationized ferritin, but apparently did not contribute directly to the
      internalization of cationized ferritin, except via the formation of coated pits
      and vesicles from their surfaces.

PMID- 8308068
TI  - Diffusible, retinal factors stimulate the barrier properties of junctional
      complexes in the retinal pigment epithelium.
AB  - The retinal pigment epithelium lies at the interface between the neural retina
      and the choriocapillaris where it forms a blood-retinal barrier. Barrier function
      requires a polarized distribution of plasma membrane proteins and 'tight' tight
      junctions. During chicken embryogenesis, these features develop gradually.
      Although terminal junctional complexes are established by embryonic day 4, the
      distribution of the Na+/K(+)-APTase is not polarized in all cells of the
      epithelium until embryonic day 11. Similarly, the tight junctions of early
      embryos are leaky, but become tight by hatching (embryonic day 21). We used
      primary cell culture to examine the molecular basis of this gradual induction of
      polarized function. Pigment epithelium harvested from embryonic day 7, and
      cultured on filters, formed monolayers coupled by junctional complexes. The
      distribution of the Na+/K(+)-ATPase was non-polarized and the tight junctions
      were leaky with a transepithelial electrical resistance of 20-30 omega cm2. To
      isolate diffusible factors that stimulate the transepithelial electrical
      resistance, neural retinas from embryonic day 7, 14 or 16 embryos were incubated
      at 37 degrees C in base medium for 6 hours. The conditioned medium was added to
      the apical chamber of freshly cultured pigment epithelium. The distribution of
      the Na+/K(+)-ATPase became basolateral, and the electrical resistance gradually
      increased two to three times over 6 days. The increase in electrical resistance
      corresponded to a decrease in the rate of [3H]inulin diffusion across the
      monolayer. The effectiveness of the conditioned medium increased steadily with
      increasing age of the neural retina. Rather than increased production of an
      active factor, apparently different active factors were produced at different
      ages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308069
TI  - Transient effect of epidermal growth factor on the motility of an immortalized
      mammary epithelial cell line.
AB  - The effects of growth factors on epithelial cell motility and dispersion have
      been examined on an immortalized human mammary epithelial cell line, the 184A1
      nontumorigenic cell line. Among all the molecules tested, epidermal growth factor
      (EGF) and transforming growth factor-alpha (TGF-alpha) were demonstrated to
      stimulate an increase in mammary epithelial cell motility and wound closure that
      was associated with a morphological transformation of the cells and was
      accompanied by modifications in cell-cell and cell-substrate adhesion systems.
      The EGF-induced increase in cell motility and monolayer wound closure occurred
      over a 24 hour period and was not dependent on an increase in cell number. The
      effect of EGF was abolished by inhibiting alpha 2 integrins with specific
      antibodies, indicating that part of the mechanism for the increase in cell
      motility and accelerated wound closure depends on alpha 2 integrin functional
      expression. After 72 hours of exposure to EGF, the EGF-induced alterations in
      cell morphology, motility and cell adhesion systems underwent a spontaneous
      reversion that was correlated with a 10-fold reduction in the number of EGF
      receptors. The ability to regulate the scattering response induced by growth
      factors might be an important feature distinguishing normal epithelial cells from
      their tumoral counterparts.

PMID- 8308070
TI  - Cultured microvascular endothelial cells (MVEC) differ in cytoskeleton,
      expression of cadherins and fibronectin matrix. A study under the influence of
      interferon-gamma.
AB  - Endothelial cells are known to undergo transitions in cell shape during long-term
      culture. Thus, the assumption that the separate phenotypes of microvascular
      endothelial cells (MVEC) recently isolated from bovine corpus luteum represent
      constitutively different cell strains cannot automatically be made. For this
      reason, particular morphological qualities from four of five reported MVEC types
      were studied. Confluent cultures of MVEC types 1, 3, 4 and 5 were either left
      untreated or exposed to recombinant bovine interferon-gamma (IFN-gamma; 200
      units/0.5 ml culture medium) for 3 days. Paraformaldehyde-fixed monolayers were
      permeabilized with Triton X-100 prior to the detection of filamentous actin,
      using phalloidin-FITC. Vimentin filaments, cytokeratin filaments, microtubules, E
      and N-cadherins as molecules of cell adhesion plaques, and fibronectin filaments
      were localized by the application of specific antibodies in combination with
      epifluorescence microscopy. Cells from untreated single cultures uniformly and
      reproducibly showed an actin cytoskeleton that distinguished the particular MVEC
      type. MVEC type 1 presented a circular band of fine actin filaments. MVEC type 3
      preferentially had developed a starburst-like actin pattern. MVEC type 4 mainly
      exhibited a polygonal network. MVEC type 5 showed a prominent circular band of
      thick microfilament bundles from which short filaments radiated. Cytokeratin
      filaments were noted in MVEC type 1 only. Vimentin filaments occurred as a dense
      network constricted to the central area in MVEC type 1, while they were spread
      out in MVEC types 3 and 4. A wavy path comparable to the course of microtubules
      was apparent in MVEC type 5. Fibronectin assembled into two differently shaped
      layers at the basal cell side of each MVEC type. Under IFN-gamma treatment,
      cytoskeletal diversities were maintained between the MVEC types, yet each MVEC
      type showed specific modulations to its cytoskeleton and to its fibronectin
      matrix. Upregulation of anti-E-cadherin labelling was detected in MVEC type 1,
      showing a fluorescent cell border of linear contour. The upregulation of E
      cadherin by IFN-gamma treatment could also be demonstrated by western blotting,
      which revealed a 135 kDa full-sized molecule and a 95 kDa tryptic fragment
      characteristic of cadherins. Anti-N-cadherin labelling was evident for MVEC type
      5, giving rise to a fluorescent punctate cell margin. Our investigations support
      the existence of truly separate MVEC types.

PMID- 8308071
TI  - The phosphotyrosine phosphatase inhibitor vanadyl hydroperoxide induces
      morphological alterations, cytoskeletal rearrangements and increased adhesiveness
      in rat neutrophil leucocytes.
AB  - The functional consequences of treating rat neutrophils with the potent tyrosine
      phosphatase inhibitor vanadyl hydroperoxide (pervanadate) has been investigated.
      Pervanadate induced rapid increases in cellular protein phosphotyrosine content
      in a dose-dependent manner. This treatment also resulted in a change in
      morphology of the cells from a rounded to a polarised morphology, with many cells
      exhibiting uropods, pseudopodia and increased membrane activity. Pervanadate
      induced a transient actin polymerisation and reorganisation similar to that in
      agonist-stimulated cells. The pervanadate-induced increases in tyrosine
      phosphorylation, shape change and actin polymerisation were inhibited by the
      tyrosine kinase inhibitors tyrphostin and erbstatin, indicating that these
      phenomena were mediated by the constitutive activity of cellular tyrosine
      kinases. Double fluorescence experiments demonstrated that there was a co
      localisation of tyrosine phosphorylated proteins with F-actin in both pervanadate
      and agonist-stimulated neutrophils. Pervanadate also induced spreading of
      neutrophils on tissue culture substrata with concurrent changes in F-actin
      localisation including unusual F-actin-containing structures. These results
      demonstrate that morphological changes and cytoskeletal reorganisation in
      neutrophils are regulated by tyrosine phosphorylation, and that inhibition of
      tyrosine phosphatase activity in neutrophils is sufficient to activate motile
      machinery of these cells. These results suggest that an alternative pathway
      involved in neutrophil stimulation might be via inhibition of endogenous tyrosine
      phosphatases rather than activation of tyrosine kinases.

PMID- 8308072
TI  - Novel developmentally regulated exon identified in the rat fast skeletal muscle
      troponin T gene.
AB  - In theory, the rat fast skeletal muscle troponin T gene can generate 64 different
      isoforms. Here we report the identification of a novel alternative exon (exon y)
      that increases the potential isoform variation to 128. The inclusion of exon y in
      fast skeletal muscle troponin T mRNA occurs in perinatal, but not adult, skeletal
      muscle. Exon y is located between exons 8 and 9. This is the first time that a
      developmentally regulated exon located amongst a set of alternatively spliced
      exons has been described. Exon y is included in two mRNA isoforms. The proteins
      that these mRNAs would encode have molecular masses greater than that of the
      largest fast skeletal muscle troponin T isoform lacking exon y. These two
      proteins correlate well in both size and pattern of expression with the two fast
      skeletal muscle troponin T isoforms expressed in perinatal skeletal muscle. These
      results indicate that there is coordinated regulation of the splicing of exon y
      with other alternative exons.

PMID- 8308073
TI  - Tektin B1 from ciliary microtubules: primary structure as deduced from the cDNA
      sequence and comparison with tektin A1.
AB  - Tektins are a class of proteins that form filamentous polymers in the walls of
      ciliary and flagellar microtubules, and they may also be present in centrioles,
      centrosomes and mitotic spindles. We report here the cloning and sequencing of a
      cDNA for ciliary tektin B1. Comparison of the predicted amino acid sequence of
      tektin B1 with the previously published sequence for tektin A1 reveals several
      features that better define this class of proteins. Like tektin A1, the central
      region of the tektin B1 polypeptide chain is predicted to form a coiled-coil rod,
      consisting of four major alpha-helical regions that are separated by non-helical
      linkers. Between the central rod domains of tektins A and B there is a 34%/20%
      amino acid sequence identity/similarity, including equivalent 50-residue segments
      containing 36 identities, and a high probability of long-range structural
      homology. The tektin polypeptide chains are divided into two major segments that
      have significant sequence homology to each other, both within a given tektin
      chain and between tektins A and B, indicative of gene duplication events. The
      tektins have a secondary structure and molecular design similar to, but a low
      primary sequence homology with, intermediate filament proteins. Unlike tektin A1,
      tektin B1 lacks any part of the C-terminal IFP consensus sequence.

PMID- 8308074
TI  - In vitro assembly properties of vimentin mutagenized at the beta-site tail motif.
AB  - The intermediate filament (IF) proteins vimentin, desmin and peripherin share a 9
      residue sequence motif (beta-site) located near the end of their COOH-terminal
      tail domain. Peptide inhibition experiments have previously suggested that the
      beta-site is involved in interactions that limit the lateral growth of IFs and
      prevent inappropriate filament-filament associations. To investigate this
      question further, we have constructed and expressed, in Escherichia coli, hamster
      vimentin bearing different mutations in the beta-site. We show here that a single
      exchange of glycine 450 with a valine residue, or an internal deletion of amino
      acids 444-452, strongly interferes with the normal assembly of IFs under in vitro
      conditions. These mutants polymerize into irregular fibrils that have a strong
      tendency to anastomose and laterally aggregate under isotonic conditions. In
      contrast, a non-conservative substitution of arginine 448 for glutamic acid does
      not significantly interfere with filament structure and yields subunits that
      polymerize into long, smooth filaments that show a slight aberration in
      thickness. All mutant proteins are soluble in low salt and form oligomers similar
      to the ones formed by wild-type vimentin. On the basis of these findings and on
      related observations, we propose that the tail domain of type III IF proteins
      contains important structural elements involved in lateral protofilament
      protofilament interactions.

PMID- 8308075
TI  - Co-localization of class II antigen and exogenous antigen in the rat enterocyte.
AB  - The role of class II major histocompatibility antigens in classical antigen
      presenting cells has been described (Unanue (1984) Annu. Rev. Immunol. 2, 395
      428; Watts and McConnell (1987) Rev. Immunol. 5, 461-475). Whether enterocytes,
      which also express class II antigens, can act as antigen-presenting cells in vivo
      is not known. One pre-requisite for a role for enterocytes in antigen
      presentation is an interaction between exogenous antigen and class II antigens.
      Our results demonstrate that class II antigen and exogenous antigen absorbed from
      the gastrointestinal tract are co-localized within endocytic compartments and
      along the basolateral membranes of enterocytes.

PMID- 8308076
TI  - HIV-induced syncytia of a T cell line form single giant pseudopods and are
      motile.
AB  - The human immunodeficiency virus, HIV, induces syncytium formation in cultures of
      many T cell lines. These syncytia have previously been viewed as disorganized
      fusion products in the throes of death. Evidence is presented that in HIV1
      infected SupT1 cultures, syncytia five times to over one hundred times larger
      than single cells organize their many nuclei into blastula-like balls, reorganize
      their cytoskeleton to mimic that of a single cell, and extend single, giant
      pseudopods in a polar fashion. Medium-sized syncytia are capable of translocation
      through extension of these giant pseudopods. The rate of translocation of
      syncytia is comparable to that of single cells. Single cell motility, syncytium
      motility and pseudopod extension also appear to play roles in the recruitment of
      cells into syncytia. Finally, condensation of F-actin at cell-syncytium and
      syncytium-syncytium adhesion sites suggests the involvement of the cytoskeleton
      in the adhesion and/or subsequent fusion event. These results suggest that the
      fusion events involved in HIV-induced syncytia formation involve both cell
      motility and reorganization of the cytoskeleton, and demonstrate that syncytia
      are highly organized, motile entities.

PMID- 8308077
TI  - Distinct roles of cdk2 and cdc2 in RP-A phosphorylation during the cell cycle.
AB  - RP-A is a single-stranded DNA-binding protein, which has been shown to be
      required for DNA replication using an SV40 model system. The protein has also
      been shown to be phosphorylated at the G1-S phase transition. Using Xenopus cell
      free extracts we have investigated the role of RP-A in nuclear replication and
      characterized the kinases and conditions that lead to phosphorylation of RP-A
      during the cell cycle. By immunodepleting RP-A from Xenopus extracts we have
      shown that RP-A is essential for replication of chromosomal DNA. Our results show
      that, during S phase, only that RP-A which is associated with nuclei is
      phosphorylated. Furthermore our results indicate that during S phase RP-A is only
      phosphorylated when associated with single-stranded DNA. By immunodepleting cdk2
      kinase we show that cdk2 kinase is required for the observed phosphorylation of
      RP-A in nuclei during S phase. However, using purified cdk2 kinase and RP-A we
      are unable to detect a direct phosphorylation of RP-A by cdk2 kinase. This
      observation suggests that phosphorylation of DNA-bound RP-A at S phase is carried
      out by a kinase distinct from cdk2. Consistent with this we find that when single
      stranded DNA is added to S phase extracts depleted of cdk2 kinase, RP-A is
      phosphorylated. Together these results suggest that cdk2 kinase participates in
      the activation of DNA replication at a stage prior to the binding of RP-A to the
      initiation complex. In addition to RP-A phosphorylation in S phase, we have also
      found that at the onset of mitosis RP-A is quantitatively phosphorylated and that
      phosphorylation is directly mediated by cdc2 kinase. However, at this time during
      the cell cycle, cdc2-dependent phosphorylation of RP-A is independent of DNA
      binding. These observations further demonstrate the distinctions between cdk2 and
      cdc2 kinases.

PMID- 8308078
TI  - Gas chromatographic-mass spectrometric method for measuring stable isotope
      enrichments of underivatized cortisol from small plasma volumes.
AB  - Isotope dilution methods utilizing quantification of stable enrichment by mass
      spectrometry has been used recently to determine cortisol production rates in
      humans. Studies of steroid production and utilization rates require frequent
      blood sampling, and while stable isotopes are safe for pediatric and perinatal
      use, the required blood volumes may be problematic using published methodologies.
      We have developed methods to isolate and quantify the plasma enrichment of
      cortisol with its stable isotope, [9,12,12-2H3]cortisol using a simple four-step
      isolation procedure and gas chromatography-mass spectrometry. Isolation is semi
      quantitative, but reproducible (mean recovery; 51.5 +/- 5.4% coefficient of
      variation) and the method does not require derivation. In human studies, this
      method can determine plasma enrichments between 1 and 10 mol% at plasma
      concentrations of 2 micrograms/dl or more; only 1 ml of plasma is required. The
      concentrations of labelled cortisol added to plasma are low (0.2-0.5
      micrograms/dl) and are not expected to interfere with the sensitive hypothalamic
      pituitary-adrenal feedback system. We conclude that reproducible quantification
      of stable cortisol isotope enrichment can be achieved from small plasma volumes.

PMID- 8308079
TI  - Rapid and sensitive gas chromatographic determination of estazolam.
AB  - The triazolobenzodiazepine estazolam can be quantitated by gas chromatography
      with electron-capture detection. After addition of a suitable internal standard,
      plasma samples are extracted into toluene-isoamyl alcohol or benzene-isoamyl
      alcohol. The organic extract is separated, evaporated to dryness, reconstituted,
      and chromatographed using a 50:50 methyl-phenyl column (SP-2250). The sensitivity
      limit is approximately 1 ng of estazolam in a 1-ml sample. The method is suitable
      for clinical or experimental pharmacokinetic studies.

PMID- 8308080
TI  - Simultaneous assay of fluoroquinolones and theophylline in plasma by high
      performance liquid chromatography.
AB  - A sensitive and selective reversed-phase high-performance liquid chromatographic
      method for the determination of theophylline in plasma simultaneously with either
      ciprofloxacin, enoxacin or norfloxacin has been developed. It involves extraction
      of plasma with chloroform-isopropanol or dichloromethane-isopropanol prior to
      chromatography on a Spherisorb ODS2 column. The mobile phase is 15% acetonitrile
      in a phosphate buffer (pH 3.0) containing tetrabutylammonium hydrogen sulphate
      (4.4 mM) as an ion-pairing agent. Ultraviolet detection is carried out at 280 nm.
      Run time is less than 10 min for all three separations. The assays have been used
      to determine the effect of plasma concentrations of fluoroquinolone on
      theophylline clearance.

PMID- 8308081
TI  - Determination of etoposide in blood by liquid chromatography with electrochemical
      detection.
AB  - A liquid chromatographic (LC) method for determination of etoposide in dog blood
      is described. The technique includes solvent extraction of etoposide using a
      dichloroethane-hexane mixture and reconstitution of the drug in an aqueous
      reconstitution solution. The samples are analyzed by reversed-phase LC with
      electrochemical detection. Validation of the method demonstrated good
      sensitivity, precision and reproducibility. The method is useful for the study of
      etoposide pharmacokinetics in the dog.

PMID- 8308082
TI  - Determination of dexfenfluramine and nordexfenfluramine in urine by high
      performance liquid chromatography using ultraviolet detection.
AB  - A method to determine the concentration of dexfenfluramine and its active
      metabolite nordexfenfluramine in human urine from healthy volunteers is described
      utilising a high-performance liquid chromatographic procedure with liquid-liquid
      extraction and ultraviolet detection. Analytes are measured after extraction of
      alkalinised urine with diethyl ether and subsequent back extraction with 0.5 M
      H2SO4 and with chromatography performed on a reversed-phase C18 column, using a
      mobile phase of acetonitrile-50 mM K2HPO4 (25:75, v/v) (flow-rate 1.3 ml/min) and
      ultraviolet detection at 210 nm. The sensitivity of the technique (10 ng/ml) is
      appropriate to measure both parent drug and metabolite in urine in humans for up
      to 5 days after a single 30-mg dose. The method is selective, reproducible
      (within- and between-day coefficient of variation ranged from 4.2 to 15%) and
      accurate (bias less than 8%) and thus suitable for dexfenfluramine
      pharmacokinetic investigations.

PMID- 8308083
TI  - Systematic approach to the development of plasma amino acid analysis by high
      performance liquid chromatography with ultraviolet detection with precolumn
      derivatization using phenyl isothiocyanate.
AB  - A reversed-phase liquid chromatographic method for the separation of 26
      phenylthiocarbamyl derivatives of amino acids in human plasma in ca. 35 min. is
      described. The method used a C18 column (150 x 4.6 mm I.D., 3 micron)
      thermostatted at 41 degrees C, and a simple multistep linear gradient of two
      solvents. Solvent A was 0.05 M sodium acetate (pH 5.1)-acetonitrile (98:2, v/v),
      and solvent B was water-acetonitrile (40:60, v/v). A simple and successful
      approach to the optimization of the conditions for the separation of the 26 amino
      acid derivatives was realized. In the initial phase of development, the
      composition of the gradient, its timings, the column temperature, the flow-rate
      and the mobile phase compositions were optimized. At the end the influence of pH
      was studied, and this approach led to a clear resolution of the 26 amino acids.
      The method was validated by accuracy, precision, and recovery studies, by
      analyzing patient samples, and by comparing the quality control sample results
      with the classical ion-exchange method.

PMID- 8308084
TI  - Hydrophobic interaction chromatography for isolation and purification of Equ.cl,
      the horse major allergen.
AB  - Equ.cl, the horse (Equus caballus) major allergen, was identified in a partially
      purified extract obtained from a crude aqueous horse dander extract, by acetonic
      precipitation and a salting-out process. It was isolated and purified by size
      exclusion chromatography followed by hydrophobic interaction chromatography.
      Equ.cl appeared as an almost pure protein in a fraction eluted at 1.2 M ammonium
      sulphate from a phenyl Superose column. It is a single peptide with a relative
      molecular mass of 20,000 and a pI of ca. 3.9.

PMID- 8308085
TI  - Advantages of paper chromatography as a preparative step in the assay of 1,25
      dihydroxyvitamin D.
AB  - Ether extraction and paper chromatography were used to separate the main
      metabolites of vitamin D in plasma [25-(OH), 24,25-(OH)2 and 1,25-(OH)2 vitamin
      D]prior to radio receptor-assay. The overall procedural loss of the 1,25-(OH)2
      vitamin D was 58 +/- 5% (n = 40), corrected for by tracer addition. The
      sensitivity of the assay was 0.5 fmol/tube, corresponding to 4 pmol/l, and the
      intra- and inter-assay coefficients of variation were 10.5% and 11.5%,
      respectively. The range of values measured in healthy controls was 80-200 pmol/l
      (n = 60), which is in agreement with findings reported in the literature. A
      comparison of the results of the present procedure with those obtained with a
      procedure employing C18 purification, disclosed a correlation coefficient of 0.92
      (p < or = 0.0001), a slope of 0.89 (p < or = 0.0001) and a small non-significant
      intercept of 5.0 pmol/l (n = 53).

PMID- 8308086
TI  - Automated sample preparation by on-line dialysis and trace enrichment. Analysis
      of morphine, 6-monoacetylmorphine, codeine, ethylmorphine and pholcodine in
      plasma and whole blood by capillary gas chromatography and capillary gas
      chromatography-mass spectrometry.
AB  - A fully automated sample preparation method for the determination of five opiates
      in human plasma and whole blood is described. The technique combines dialysis and
      trace enrichment prior to gas chromatography and gas chromatography-mass
      spectrometry. Dialysis and trace enrichment on a polymer column was shown to be a
      highly reliable method for sample preparation. The method can be used, after
      minor modification, to determine other basic drugs in plasma and whole blood. The
      method demonstrates the potential of the automated sequential trace enrichment of
      dialysate (ASTED) system for automated sample preparation.

PMID- 8308087
TI  - Identification of radiolabeled metabolites of nicotine in rat bile. Synthesis of
      S-(-)-nicotine N-glucuronide and direct separation of nicotine-derived conjugates
      using high-performance liquid chromatography.
AB  - Four metabolites of nicotine, including two glucuronides, have been separated by
      high-performance liquid chromatography. This separation was applied to
      identification of biliary metabolites of radiolabeled nicotine by radiometric
      detection. S-(-)-Nicotine N-glucuronide was synthesized and used as a standard in
      method development.

PMID- 8308088
TI  - Determination of rocuronium and its putative metabolites in body fluids and
      tissue homogenates.
AB  - A sensitive and selective HPLC method was developed for the quantification of the
      neuromuscular blocking agent rocuronium and its putative metabolites (the 17
      desacetyl derivative and the N-desallyl derivative of rocuronium) in plasma,
      urine, bile, tissue homogenates and stoma fluid. Samples were prepared by
      extraction of the biological matrix with dichloromethane, after mixing with a KI
      glycine buffer. After evaporation of the organic solvent the samples were
      chromatographed on a reversed-phase HPLC column, using an aqueous buffer-dioxane
      (84:16, v/v) as the mobile phase. The aqueous buffer consisting of 0.1 M sodium
      dihydrogen phosphate, 0.11 mM 9,10-dimethoxyanthracene-2-sulphonate (DAS), 0.11
      mM 1-heptane-sulfonic acid, was adjusted to pH 3 with orthophosphoric acid. After
      separation, the eluent was extracted with dichloroethane, and the organic phase
      was led to a fluorimetric detector, operating at 385 nm (excitation) and 452 nm
      (emission). The method was validated for the assay in plasma, urine, bile, tissue
      homogenates and stoma fluid, by determination of the repeatability,
      reproducibility, accuracy, lower limit of quantification, lower limit of
      detection, extraction recovery, effect of sample volume, and stability in the
      biological matrix. The method was found to be sensitive (lower limit of
      quantification for rocuronium in plasma is 10 ng/ml) and accurate. The
      interference of concomitant drugs with the assay of rocuronium and its putative
      metabolites has been studied extensively. In order to confirm the identity of
      rocuronium and its putative metabolites, a TLC method was developed. The method
      has been applied successfully in several pharmacokinetic studies with rocuronium.

PMID- 8308089
TI  - Automated headspace gas chromatographic analysis of faecal short-chain fatty
      acids.
AB  - A method was developed and validated for analysis of faecal short-chain fatty
      acids using automated headspace gas chromatography. Quantification was by
      standard addition. Ghosting was minimized by lining the transfer tube from the
      headspace sampler to the gas chromatograph with deactivated fused silica and
      addition of formic acid to sample vials. Saturation of samples with lithium
      sulphate increased recoveries. The method was used to analyse small amounts of
      faecal matter collected from premature babies. Advantages of the technique are
      rapid, accurate, analysis of faecal specimens in batches, with minimum sample
      preparation.

PMID- 8308090
TI  - Highly sensitive high-performance liquid chromatography for the measurement of
      malondialdehyde in biological samples.
AB  - A highly sensitive method for the measurement of malondialdehyde as
      thiobarbituric acid-malondialdehyde complex by reversed-phase high-performance
      liquid chromatography with fluorescence detection in biological samples is
      described. As samples, 20 microliters of rat plasma or 10% (w/v) liver homogenate
      mixed with 2.0% thiobarbituric acid in 2 M sodium acetate buffer containing 0.05%
      butyl hydroxytoluene (pH 3.5) were heated at 95 degrees C for 45 min to give the
      complex. The complex, extracted with n-butanol, was chromatographed on a system
      equipped with a reversed-phase column, and the eluted peak was monitored with a
      fluorescence detector (excitation wavelength 515 nm, emission wavelength 553 nm).
      The mobile phase was a acetonitrile-water (2:8, v/v) under isocratic conditions
      at ambient temperature, and a single analysis was done in ca. 4 min. The minimum
      detection level for malondialdehyde was as low as 0.05 pmol. The n-butanol
      extract was stable at least for 3 days. The simple mobile phase, the extremely
      sensitive detection limit, and the stability of the complex make this system
      applicable to routine clinical analysis with a small amount of tissue or biopsy
      sample.

PMID- 8308091
TI  - Breakdown of 3,4-dihydroxybenzylamine and dopamine in plasma of various animal
      species by semicarbazide-sensitive amine oxidase.
AB  - We report a rapid breakdown of dopamine and especially of 3,4
      dihydroxybenzylamine, the frequently-used internal standard in catecholamine
      determinations, in plasma of many but not all animal species. Species
      investigated were cow, sheep, goat, pig, horse, rabbit, dog, guinea pig, mouse,
      chicken, rat and man. In some species 3,4-dihydroxybenzylamine nearly completely
      disappeared at 4 degrees C within 15 min after addition to the plasma. Added
      dopamine, but not norepinephrine and epinephrine, also rapidly disappeared at 4
      degrees C. Disappearance rates were increased at higher temperatures, and at 20
      degrees C also norepinephrine showed some breakdown. The breakdown is caused by a
      semicarbazide-sensitive amine oxidase in the plasma, and can be completely
      blocked by the addition of the inhibitor semicarbazide. Measurement of plasma
      catecholamine concentrations in animal species can thus lead to erroneous
      results, especially when 3,4-dihydroxybenzylamine is used as an internal
      standard. Only when blood is collected in tubes containing an inhibitor of
      semicarbazide-sensitive amine oxidase like semicarbazide can reliable plasma
      catecholamine measurements be performed.

PMID- 8308092
TI  - Gas chromatographic-mass spectrometric determination of plasma and brain cocaine
      in mice.
AB  - A gas chromatographic-mass spectrometric method is described for the
      determination of cocaine in mouse plasma microsamples and brain. Cocaine and
      [2H3]cocaine were extracted with pentane-isopropyl alcohol (97:3, v/v),
      chromatographed on a (5% phenyl) methylpolysiloxane capillary column, and
      detected by selected-ion monitoring of electron impact generated m/z 182 and 185
      fragment ions. The small sample size (50 microliters), simplicity of workup, and
      high response linearity (mean r = 0.9993) distinguish the method. Cocaine was
      found in mouse brain at approximately 5 times greater concentration than in
      plasma after 20 or 40 mg/kg subcutaneous doses.

PMID- 8308093
TI  - Determination of nifedipine in gingival crevicular fluid: a capillary gas
      chromatographic method for nifedipine in microlitre volumes of biological fluid.
AB  - This paper describes a sensitive capillary gas chromatographic (GC) method for
      the determination of nifedipine in sub-microliter samples of gingival crevicular
      fluid (GCF) in order to assess if nifedipine is present in the GCF and if so,
      whether the local tissue concentrations of this drug are an important determinant
      in the development of gingival overgrowth. Liquid-liquid and solid-phase
      extraction were combined to give adequate sample clean-up and concentration for
      measurement by automated capillary GC with electron capture detection. Nifedipine
      and its principal metabolite, M-I, were analysed in both plasma and GCF in 9
      adult male patients who had been taking nifedipine for over six months. M-I could
      not be measured in GCF. Plasma nifedipine and M-I levels were normal, but the
      nifedipine levels found in the GCF of 7 patients (including all those with
      overgrowth) were remarkably elevated, 15 to 316-fold greater. This massive
      concentration of nifedipine into the GCF is therefore linked with gingival
      overgrowth. This is the first time that a GC method has been developed which
      permits determination of GCF pharmacokinetics of a drug which causes gingival
      overgrowth, and further investigation will lead to a better understanding of the
      tissue mechanisms involved.

PMID- 8308094
TI  - Determination of chlorinated insecticides in blood samples of agricultural
      workers.
AB  - Lindane, aldrin and p,p'-DDT were determined in blood samples from 71 farmers by
      means of an analytical method which combines a direct whole-blood extraction with
      n-hexane and gas chromatography (GC)-electron-capture detection (ECD), using a
      capillary column, applied to the organic extract. This technique allowed the
      determination of pesticides at levels varying from 0.1 to 180 micrograms per l of
      blood, the detection limit for every pesticide being 0.1 microgram/l. GC-mass
      spectrometry was used to confirm the identity of each pesticide. The advantage of
      capillary column GC-ECD for pesticide determination is its sensitivity and high
      resolution, which makes it possible to separate pesticides from a complex n
      hexane extract obtained in a very simple pretreatment of the blood sample, which
      is itself a very complex matrix.

PMID- 8308095
TI  - Determination of clenbuterol and salbutamol in urine by capillary gas
      chromatography with capillary columns of 100 microns.
AB  - A method to determine clenbuterol and salbutamol in calf urine is described. Two
      independent extraction procedures using Extrelut (clenbuterol) and
      octadecylsilica (salbutamol) were used; the extracts obtained were mixed and
      purified over a cyanopropyl minicolumn. Trimethylsilyl derivatives were prepared
      and analysed by GC-MS in selected-ion monitoring mode using a fused-silica open
      tubular capillary column, 10 m x 100 microns coated with 5% phenylmethylsilicone.
      Splitless injection was optimized to achieve low percentage residual standard
      deviation of absolute areas. The best conditions were: injection volume 0.5
      microliter, column head pressure 22 p.s.i. (1 p.s.i. = 6894.76 Pa), inlet
      temperature 250 degrees C and glass liner volume 250 microliters. The recoveries
      of the complete procedure were in the range 50-60% for both compounds.

PMID- 8308096
TI  - Separation and characterization of rat kidney isometallothioneins induced by
      exposure to inorganic mercury.
AB  - High-performance liquid chromatography (HPLC) was applied to the separation of
      metallothionein (MT) isoforms from different tissues from a variety of eukaryotic
      species. Recently we reported an analytical method for 203Hg-metallothionein,
      which detects the radioisotope bound to each iso-MT after separation by HPLC on a
      size-exclusion column coupled with on-line radioactivity flow detection. The MTs
      can be separated as distinct isoprotein peaks by elution with alkaline buffer
      solution owing to cation-exchange chromatographic action. In the present work,
      renal MT from rats exposed to inorganic mercury was separated into four peaks by
      UV and 203Hg detection. Moreover, it was resolved into four components by non
      denaturing polyacrylamide gel electrophoresis. The two major components
      correspond to MT-1 and MT-2, which were characterized by amino acid analysis.
      Finally, Hg induces and binds to both iso-MTs.

PMID- 8308097
TI  - Liquid chromatography and radioimmunoassay method for the determination of
      prostaglandins E1 and E2 in rat embryo incubates.
AB  - This paper describes the application of a combined high-performance liquid
      chromatography and radioimmunological assay method for the measurement of
      prostaglandins E1(PGE1) and E2(PGE2). Samples were acidified to pH 3.15,
      extracted twice with ethyl acetate and further processed through C18 solid-phase
      extraction cartridges. After HPLC purification, PGE1 and PGE2 were measured by
      radioimmunological techniques. The limit of detection for PGE1 was 3.9 pg/ml and
      the intra-assay relative standard deviation was 7.8% for n = 5. The accuracy of
      the assay procedure was also verified. The method has been applied to the
      determination of PGE1 and PGE2 in embryo incubates from 10-day pregnant rats.

PMID- 8308098
TI  - High-performance liquid chromatographic determination of plasma triglyceride type
      composition in a normal population of Barcelona. Relationship with age, sex and
      other plasma lipid parameters.
AB  - A coupled TLC-HPLC procedure is proposed for the separation and determination of
      plasma triglycerides. The method was tested by application to plasma samples
      corresponding to a normal population of Barcelona (Spain). Eighteen different
      triglyceride types were identified and their relative proportions were
      established, in order to give a "normal profile" for men and women. Sex-related
      differences (p < 0.05) were only found for dioleostearin and palmitodilinolein +
      linoleooleopalmitolein (LLP+LOPa). A correlation study showed that palmitodiolein
      and total cholesterol levels increase with age, whereas LLP-LOPa decreases in men
      and palmitolinoleoolein + palmitooleopalmitolein in women.

PMID- 8308099
TI  - Supercritical fluid extraction of fluvalinate residues in honey. Determination by
      high-performance liquid chromatography.
AB  - A method for the analysis of fluvalinate residues in honey from beehives treated
      with this product to prevent varroatosis is described. The method involves
      supercritical fluid extraction with carbon dioxide and further analysis by high
      performance liquid chromatography on a C18 reversed-phase column, acetonitrile
      water (80:20) as mobile phase and detection at 254 nm. This method is simpler
      than the one in which extraction with organic solvents, thin-layer chromatography
      and gas chromatography is used.

PMID- 8308100
TI  - Serodiagnosis in early Lyme disease.
AB  - Using a commercially available enzyme-linked immunosorbent assay (ELISA) and an
      immunoblot assay (IB), we tested sera from 100 patients with erythema migrans
      (EM) seen in 1991 a the Westchester County Medical Center Lyme Disease Diagnostic
      Center. Convalescent-phase sera were available from 59 patients. Fifty-five
      patients had EM of < 7 days' duration, 31 had EM of 7 to 14 days' duration, and
      14 had EM of > 14 days' duration. During the acute phase of infection, 35
      patients had a positive ELISA result and 43 had a positive IB result by the
      recently published criteria of Dressler et al. (F. Dressler, J. A. Whalen, B. N.
      Reinhardt, and A. C. Steere, J. Infect. Dis. 167:392-400, 1993) for
      interpretation of IB in patients with Lyme disease. A greater sensitivity of IB
      was observed in patients with EM of < 7 days' duration, as follows: 14 of 55
      (25%) for IB versus 7 of 55 (13%) for ELISA (P = 0.144). Sera of all 14 patients
      with EM of > 14 days' duration were reactive by both tests, as follows: 13
      positive and 1 equivocal by ELISA and 12 positive and 2 indeterminate by the IB.
      The band reactivity most frequently observed in the IB was to the 41- and 25-kDa
      antigens, the latter being the most frequent band observed in immunoglobulin M
      blots. Seroconversion was observed in 74 and 64% of evaluable patients by ELISA
      and IB, respectively, despite the use of antibiotic therapy.

PMID- 8308101
TI  - Distribution and molecular analysis of Lyme disease spirochetes, Borrelia
      burgdorferi, isolated from ticks throughout California.
AB  - Previous studies describing the occurrence and molecular characteristics of Lyme
      disease spirochetes, Borrelia burgdorferi, from California have been restricted
      primarily to isolates obtained from the north coastal region of this large and
      ecologically diverse state. Our objective was to look for and examine B.
      burdorferi organisms isolated from Ixodes pacificus ticks collected from numerous
      regions spanning most parts of California where this tick is found. Thirty-one
      isolates of B. burgdorferi were examined from individual or pooled I. pacificus
      ticks collected from 25 counties throughout the state. One isolate was obtained
      from ticks collected at Wawona Campground in Yosemite National Park, documenting
      the occurrence of the Lyme disease spirochete in an area of intensive human
      recreational use. One isolate from an Ixodes neotomae tick from an additional
      county was also examined. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, immunoblot analysis, agarose gel electrophoresis, Southern blot
      analysis, and the polymerase chain reaction were used to examine the molecular
      and genetic determinants of these uncloned, low-passage-number isolates. All of
      the isolates were identified as B. burgdorferi by their protein profiles and
      reactivities with monoclonal and polyclonal antibodies, and all the isolates were
      typed by the polymerase chain reaction as North American-type spirochetes (B.
      burgdorferi sensu stricto). Although products of the ospAB locus were identified
      in protein analyses in all of the isolates, several isolates contained deleted
      forms of this locus that would result in the expression of chimeric OspA-OspB
      proteins. The analysis of OspC demonstrated that this protein was widely
      conserved among the isolates but was also quite variable in its molecular mass
      and the amount of it that was expressed.

PMID- 8308102
TI  - Establishment of a quality assurance program for human immunodeficiency virus
      type 1 DNA polymerase chain reaction assays by the AIDS Clinical Trials Group.
      ACTG PCR Working Group, and the ACTG PCR Virology Laboratories.
AB  - An independent quality assurance program has been established by the Virology
      Committee of the AIDS Clinical Trials Group in the Division of AIDS, National
      Institute of Allergy and Infectious Diseases, for monitoring polymerase chain
      reaction (PCR) assays for human immunodeficiency virus type 1 (HIV-1) DNA that
      are performed by 11 laboratories participating in multicenter clinical trials in
      the United States. To perform HIV-1 DNA PCR for patients in AIDS Clinical Trials
      Group protocols, each laboratory was initially certified by correctly testing a
      coded certification panel consisting of eight well-defined clinical whole-blood
      specimens and 30 cell pellets containing 0, 2, 5, 10, 20, or 50 8E5/LAV cells per
      125,000 uninfected peripheral blood mononuclear cells. PCR was performed by one
      of two standardized commercial assays for amplification and nonisotopic detection
      of HIV-1 proviral DNA. For continuing certification, each laboratory must
      correctly test eight coded whole-blood samples per quarter and run three or four
      coded cell pellets and HIV-1 DNA copy standards with every PCR assay in real
      time. The PCR results for the coded pellets on each run are entered into an
      encrypted computer file, which immediately assesses the validity of the run. To
      date, 10 of 11 laboratories have correctly tested all HIV-1-positive and 
      negative samples in the initial certification panel on their first or second
      attempt. Subsequently, 9 of these 11 laboratories have continued to maintain
      their certified status. The use of commercial HIV-1 DNA PCR assays and an
      external quality assurance program have ensured that results from different
      laboratories are comparable and that problems with sensitivity and specificity
      are quickly identified.

PMID- 8308103
TI  - Development of a rapid and sensitive polymerase chain reaction assay for
      detection of bovine herpesvirus type 1 in bovine semen.
AB  - We developed a polymerase chain reaction (PCR) assay to detect bovine herpesvirus
      type 1 (BHV-1) in bovine semen. Since bovine semen contains components that
      inhibit PCR amplification, a protocol was developed to purify BHV-1 DNA from
      bovine semen. To identify failures of PCR amplification, we used an internal
      control template that was coamplified by the same PCR primers. When separated
      fractions of BHV-1-contaminated semen were analyzed by the PCR, we found that
      more than 90% of the BHV-1 DNA was present in a pooled fraction consisting of
      seminal fluid, nonsperm cells, and virus adsorbed to spermatozoa. By using this
      fraction, three to five molecules of BHV-1 DNA in 50 microliters of bovine semen
      could be detected. A pilot study to compare this PCR assay with the routinely
      used virus isolation method showed that this PCR assay is 2- to 100-fold more
      sensitive. In addition, the results of the PCR assay are available in 1 day,
      whereas the virus isolation method takes 7 days. Therefore, the PCR assay may be
      a good alternative to the virus isolation method.

PMID- 8308104
TI  - Comparative analysis of Brucella serotype A and M and Yersinia enterocolitica O:9
      polysaccharides for serological diagnosis of brucellosis in cattle, sheep, and
      goats.
AB  - Hapten polysaccharides of Brucella smooth M and A serotypes were prepared from
      Brucella sp. and Yersinia enterocolitica O:9 by previously described hydrolytic
      (O chain) or nonhydrolytic (native hapten [NH]) procedures. The purified
      polysaccharides differed only in the presence (O chain) or absence (NH) of
      lipopolysaccharide core sugars. The polysaccharides were compared by reverse
      radial immunodiffusion for the diagnosis of brucellosis in cattle (Brucella
      abortus biotype 1 [A serotype] and Brucella melitensis biotype 3 [AM serotype]),
      sheep (B. melitensis biotypes 1 [M serotype] and 3), and goats (B. melitensis
      biotype 1). The reverse radial immunodiffusion test with the NH from B.
      melitensis 16 M (serotype M) showed the highest sensitivity (89.6 to 97.3%),
      regardless of the host species and the serotype of the infecting Brucella sp. Y.
      enterocolitica O:9 NH (A serotype) was useful for diagnosing disease in cattle
      infected with B. abortus biotype 1, but not in cattle infected with B. melitensis
      biotype 3, sheep, or goats. The different results obtained with the serotype M
      and A polysaccharides and the sera from animals infected with M, A, and AM
      serotypes of Brucella spp. showed that in naturally infected animals, a large
      proportion of the antibodies are directed to or react with a previously defined
      common epitope(s) (J. T. Douglas and D. A. Palmer, J. Clin. Microbiol. 26:1353
      1356, 1988) different from the A or M epitopes. By using the radial
      immunodiffusion test with B. melitensis 16M NH, it was possible to differentiate
      infected from vaccinated cattle, sheep, and goats with a sensitivity and
      specificity similar to that of the complement fixation test.

PMID- 8308105
TI  - Use of a monoclonal antibody in a dot immunobinding assay for detection of a
      circulating mannoprotein of Candida spp. in neutropenic patients with invasive
      candidiasis.
AB  - A dot immunobinding assay for the detection of a circulating mannoprotein (MP)
      antigen of Candida species in the sera of neutropenic patients in a hematological
      setting is described. The technique is based on the use of a monoclonal antibody
      which recognizes an oligomannoside epitope shared by distinct MP of pathogenic
      Candida species. The sensitivity of the assay for antigen detection in serum was
      between 2 and 5 ng/ml, and MPs from Candida albicans, Candida tropicalis,
      Torulopsis glabrata, and Candida parapsilosis, but not Candida krusei, could be
      detected. A retrospective analysis of sera from patients with proven invasive
      candidiasis versus sera from controls (Candida-colonized and noncolonized
      subjects) revealed that the novel assay has sufficient sensitivity, specificity,
      and predictive values to be of potential diagnostic significance.

PMID- 8308107
TI  - Evaluation of a technique for identification of Shiga-like toxin-producing
      Escherichia coli by using polymerase chain reaction and digoxigenin-labeled
      probes.
AB  - A polymerase chain reaction (PCR) technique for the identification of Shiga-like
      toxin (SLT)-producing Escherichia coli was assessed by using 95 strains of SLT
      producing E. coli and 5 Shigella dysenteriae type 1 strains. PCR was used for the
      amplification of slt gene sequences from whole bacterial colonies. A digoxigenin
      labeled DNA probe was used for identification of the PCR products in a spot blot
      hybridization assay. Modifications were made to adapt this technique for the
      proper identification of 10 SLT-producing isolates which were refractory to the
      heat lysis step that was used to liberate whole-cell DNA for PCR and 6 isolates
      which gave nonspecific amplification products. The sensitivity and specificity of
      this assay were each 99% when compared with toxin neutralization results by using
      SLT-specific monoclonal antibodies. These values indicate that this detection
      technique could be suitable for use in a clinical laboratory.

PMID- 8308106
TI  - Reliable confirmation of antibodies to bovine respiratory syncytial virus (BRSV)
      by enzyme-linked immunosorbent assay using BRSV nucleocapsid protein expressed in
      insect cells.
AB  - The nucleocapsid (N) protein of bovine respiratory syncytial virus (BRSV) in the
      baculovirus expression system was evaluated as a source of antigen in an enzyme
      linked immunosorbent assay (ELISA) for the detection of respiratory syncytial
      virus (RSV) antibodies. The recombinant N protein was purified from infected-cell
      extracts by sucrose gradient centrifugation and used in the ELISA for the
      detection of antibodies to various RSV strains. The ELISA was compared with the
      virus neutralization (VN) test for determining BRSV antibodies in 10 consecutive
      serum samples from four calves vaccinated with a live modified BRSV vaccine and
      from two nonvaccinated control calves. The ELISA compared favorably with the VN
      test for detecting serological responses. All serum samples which were positive
      in the VN test were also positive in the ELISA. None of the serum samples
      collected from the two nonvaccinated calves reacted in the ELISA. To determine
      the usefulness of the ELISA for epidemiological studies, 58 cattle serum samples
      were tested in the ELISA and the VN test. Approximately 94% (42 of 45) of field
      serum samples which were positive in the ELISA were also positive in the VN test.
      No case was found in which the ELISA result was negative and the VN test result
      was positive. Thirteen of the serum samples were negative in both methods. Our
      results indicate that the ELISA with the baculovirus-expressed N protein as an
      antigen is an efficient, sensitive, and specific method for detecting serum
      antibodies to RSV.

PMID- 8308108
TI  - Parallel comparison of accuracy of API 20E, Vitek GNI, MicroScan Walk/Away Rapid
      ID, and Becton Dickinson Cobas Micro ID-E/NF for identification of members of the
      family Enterobacteriaceae and common gram-negative, non-glucose-fermenting
      bacilli.
AB  - We compared the API 20E (21 h) (API; bioMerieux Vitek, Hazelwood, Mo.), the Vitek
      GNI card (4 to 18 h) (Vitek; bioMerieux Vitek), the identification portion of the
      MicroScan Walk/Away Rapid Neg Combo 3 panel (2 h) (W/A; Baxter Diagnostics, Inc.,
      West Sacramento, Calif.), and the Becton Dickinson Cobas Micro ID-E/NF rotor (21
      h) (Cobas; Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.), versus
      conventional biochemicals for their abilities to identify accurately 252 strains
      of biochemically typical and atypical members of the family Enterobacteriaceae
      and common non-glucose-fermenting gram-negative bacilli. All strains used were
      included in the data base of each product. At the end of the initial incubation,
      194 (77.0%), 213 (84.5%), 198 (78.6%), and 192 (76.2%) strains were correct to
      the genus and species levels with the API, Vitek, W/A, and Cobas systems,
      respectively. After additional biochemical tests were performed, as directed by
      each manufacturer's protocol, the numbers of strains correctly identified to the
      genus and species levels were 241 (95.6%), 234 (92.8%), 243 (96.4%), and 230
      (91.3%) with the four systems, respectively. The errors were random in all
      systems, with the exception of two atypical Salmonella enteritidis strains, each
      of which was misidentified by three systems. After the initial recommended
      incubation period, both API and Cobas were significantly less accurate than Vitek
      (Yates' corrected P < 0.05). No significant differences were noted between the
      results of Vitek and W/A or between the results of API and W/A. After additional
      tests were completed, Cobas was significantly less accurate than W/A (P < 0.05)
      but was equal in accuracy to Vitek and API. API, Vitek, and W/A were equal in
      accuracy after these same additional tests. All four systems were significantly
      more accurate after additional biochemical testing than after the initial
      reporting period (194 of 252 versus 241 of 252 for API, 213 of 252 versus 234 of
      252 for Vitek, 198 of 252 versus 243 or 252 for W/A, and 192 of 252 versus 230 of
      252 for Cobas [P<0.05]).

PMID- 8308109
TI  - Evaluation of Biolog for identification of members of the family Micrococcaceae.
AB  - The Biolog Identification System (Biolog, Inc., Hayward, Calif.) was challenged
      at two separate laboratories with 113 coded isolates, including 33 type strains
      of staphylococci, 5 strains of Micrococcus spp., and 1 strain of Stomatococcus
      mucilaginosus. Test parameters between the sites were controlled as much as
      possible. Discrepancies were arbitrated by using conventional biochemicals.
      Overall accuracies (correct to the species level) upon initial testing were 47.7
      and 59.3%, respectively, at the two laboratories. After repeat testing of
      isolates generating "no identification" responses or errors, the overall
      accuracies increased to 69.0 and 74.3% at the two sites, respectively, revealing
      no significant difference in the final results at the two laboratories (78 of 113
      versus 84 of 113; P > 0.05). Error rates were 7.1% at one site and 9.7% at the
      other. The Biolog is not yet accurate enough to serve as a primary method for
      identifying staphylococci.

PMID- 8308110
TI  - Genetic similarity and phenotypic diversity of commensal and pathogenic strains
      of Candida albicans isolated from the oral cavity.
AB  - Colony phenotype and genetic similarity were assessed within and between groups
      of commensal and pathogenic strains of Candida albicans collected from the oral
      cavities of individuals in a single geographical locale. Thirty-eight percent of
      pathogenic isolates contained predominant or minor variant colony morphologies
      (other than smooth) when samples from the sites of infection were cultured on
      plates, while 16% of commensal isolates contained minor variant colony
      morphologies when samples from the sites of carriage were cultured. The genetic
      similarities of isolates within and between groups were assessed by DNA
      fingerprinting by using Southern blot hybridization with the fingerprinting probe
      Ca3 and analysis with the computer-assisted, automated Dendron system. Both the
      commensal and the pathogenic groups contained a major cluster of genetically
      similar C. albicans isolates representing 31 and 33% of the strains in the
      respective groups. When a combined dendrogram of both commensal and pathogenic
      isolates was generated, the major clusters of genetically similar isolates in
      each group mixed into one large cluster. Minor clusters in the individual
      dendrograms also mixed. These results suggest common clonal origins for commensal
      and pathogenic strains in the same geographical locale.

PMID- 8308111
TI  - Factors affecting detection of Brucella melitensis by BACTEC NR730, a
      nonradiometric system for hemocultures.
AB  - The detection of Brucella bacteremia by subculture does not always correlate with
      a positive signal in the BACTEC NR730 nonradiometric system (Becton Dickinson
      Diagnostic Instrument Systems, Sparks, Md.). The effect of the inoculum size, pH,
      sodium polyanetholesulfonate, carbon sources (i-erythritol, sodium pyruvate,
      monosodium glutamate, D-glucose, and L-alanine), and urea in the release of CO2
      was evaluated by using the reference strain Brucella melitensis 16M. In standard
      NR6 vials with or without blood, inocula 5 to 10 times larger (at least 265 CFU
      per vial) than those usually found in the blood of patients with brucellosis were
      necessary to produce a positive growth value (GV) in 4 days or less, and similar
      results were obtained with vials supplemented with the substrates listed above.
      GVs were consistently lower in vials with sodium polyanetholesulfonate than in
      vials without this agent. Vials with no blood inoculated with 265 CFU per vial
      showed turbidity 1 day before GVs became positive, proving that the major
      limiting detection factor was the low level of release of CO2 and not an
      inadequate growth medium. In NR6 vials buffered to pH 6.2, GVs became positive
      faster and were higher than those in standard vials. NR6 vials at pH 6.2 with
      0.3% sodium pyruvate yielded a positive GV in the first day of bacterial
      turbidity.

PMID- 8308112
TI  - Evaluation of Clearview and Magic Lite tests, polymerase chain reaction, and cell
      culture for detection of Chlamydia trachomatis in urogenital specimens.
AB  - The Clearview Chlamydia test (CV; Unipath Ltd., Bedford, United Kingdom), the
      Magic Lite Chlamydia test (ML; CIBA Corning, Medfield, Mass.), a polymerase chain
      reaction (PCR), and cell culture (CC) were evaluated for detection of Chlamydia
      trachomatis in urogenital specimens. Specimens were collected from 283 men and
      724 women visiting the outpatient clinic for Sexually Transmitted Diseases at the
      University Hospital Rotterdam, Rotterdam, The Netherlands. ML, PCR, and CC were
      all performed on the same sample to prevent swab-to-swab variability. CV was
      performed on a separate sample. Analysis of discordant results was performed by
      application of the following confirmatory assays: first, PCR on the CC, second,
      ML was repeated, and third, PCR was repeated by using a different DNA extraction
      protocol. If more than one test was positive, the sample was considered true
      positive. If only one test was positive, which was confirmed by the confirmatory
      assay, the sample was also considered true positive. By using these
      interpretations, the following results were obtained. The sensitivity and
      specificity of CV for samples from men were 60.4 and 86.3%, respectively. For
      samples from women, these values were 62.3 and 99.7%, respectively. The low
      specificity for samples from men was caused by unidentified substances in the
      swab that was used. The use of CV on samples from men is not recommended by the
      manufacturer. For samples from women, the specificity of CV was high, but the low
      sensitivity of CV limits its use for diagnostic purposes. The sensitivities of ML
      were low for samples from both men and women (68.8% and 50.9% respectively),
      while specificities were excellent for samples from both groups (100 and 99.9%,
      respectively). The low sensitivity of ML limits its diagnostic value. The PCR
      technique was highly specific for samples from both men (99.6%) and women
      (99.9%). The sensitivity of PCR, however, was unexpectedly low for samples from
      both groups (men, 87.5%; women, 79.2%), most likely because of the sample
      treatment method used. The sensitivity and specificity values of CC for samples
      from men were 95.8 and 100%, respectively. For samples from women, these values
      were 100 and 99.9%, respectively. In the present study, CC was the most reliable
      technique for the detection of C. trachomatis.

PMID- 8308113
TI  - Serological differentiation between cystic and alveolar echinococcosis by use of
      recombinant larval antigens.
AB  - Two recombinant antigens of the larval stages of Echinococcus granulosus and
      Echinococcus multilocularis, termed EG55 and EM10, respectively, were applied for
      serodiagnosis and serological differentiation between parasitic infections caused
      by the metacestode tissue of both tapeworms. Antigen EM10 is synthesized by E.
      multilocularis larvae. Antigen EG55 represents the recombinant form of the low
      molecular-weight subunit of antigen B, which is an Echinococcus genus-specific
      antigen. Both recombinant antigens were expressed as glutathione S-transferase
      fusion proteins. A sandwich enzyme-linked immunosorbent assay with monoclonal
      antibodies against EM10 and EG55 as capture reagents for the recombinant antigens
      was established and was evaluated with 74 serum samples from patients with
      histologically confirmed alveolar echinococcosis and 63 serum samples from
      patients with histologically confirmed cystic echinococcosis. A sensitivity of
      93.2% and a specificity of 96.8% were achieved for the serodiagnosis of alveolar
      echinococcosis. Cystic echinococcosis could be detected with a sensitivity of
      89.1% and a specificity of 98.6%.

PMID- 8308114
TI  - Effects of media, atmosphere, and incubation time on colonial morphology of
      Arcanobacterium haemolyticum.
AB  - Arcanobacterium haemolyticum causes pharyngitis as well as skin and other wound
      infections. Although it is a beta-hemolytic organism, the hemolysis is less well
      defined than that of beta-hemolytic streptococci and may be overlooked in
      cultures with heavy growth of commensal throat flora. To determine whether
      routine throat culture conditions are sufficient to produce recognizable colonies
      of A. haemolyticum, the morphology of six distinct strains was studied after
      various combinations of incubation time, medium, and atmosphere. The agar media,
      containing 5% sheep blood, were Trypticase soy agar, Columbia agar, and heart
      infusion agar. Cultures were incubated in ambient air, 6 to 8% CO2, or an
      anaerobic atmosphere. Cultures were compared after 24, 48, and 72 h of incubation
      for colony size, clarity and size of hemolytic zone, and macroscopic evidence of
      agar pitting. A minimum of 48 h was needed for expression of beta-hemolysis and
      pitting. Trypticase soy agar was the superior medium and CO2 was the superior
      atmosphere for beta-hemolysis. Agar pitting was not significantly affected by
      variations in medium or atmosphere. Strains differed in their expression of
      hemolysis and production of pits at 48 h. After 72 h of incubation, beta
      hemolysis and pitting were visible in over 96% of culture observations.

PMID- 8308115
TI  - Isolation of Mycobacterium avium complex from water in the United States,
      Finland, Zaire, and Kenya.
AB  - Disseminated infection with organisms of the Mycobacterium avium complex (MAC) is
      a common complication of AIDS in the United States and other developing
      countries, but it is rare or absent in sub-Saharan Africa. To assess the
      comparative likelihood of exposure to MAC in these geographic areas, we used a
      standard protocol to culture 91 water samples from environmental sites and piped
      water supply systems in the United States, Finland, Zaire, and Kenya. MAC was
      isolated from all geographic areas and from 22 of 91 (24%) samples. Isolation
      rates were 13 of 47 (28%) for environmental samples and 9 of 44 (20%) for water
      supply samples. Overall isolation rates were 18 of 52 (35%) samples in the United
      States and Finland, whereas they were 4 of 39 (10%) samples in Zaire and Kenya (P
      = 0.015). MAC isolation rates from water supply systems were 8 of 25 (32%)
      samples in the United States and Finland and 1 of 19 (5%) samples in Zaire and
      Kenya (P = 0.056). MAC was isolated from hospital water in the United States and
      Finland but not in hospital water in Zaire and Kenya. Serovar determinations
      showed that six of eight isolates from the United States were serovar 4 or 8. One
      MAC isolate from Zaire was identified as an "X" mycobacterium. These data suggest
      that exposure to MAC in water is likely in diverse areas of the world, but that
      the likelihood of human exposure to the organism in water may be slightly less in
      sub-Saharan Africa than in developed countries in the Northern Hemisphere.

PMID- 8308116
TI  - Clinical significance, biochemical features, and susceptibility patterns of
      sporadic isolates of the Mycobacterium chelonae-like organism.
AB  - Mycobacterium chelonae-like organisms are nonpigmented rapidly growing
      mycobacteria whose clinical significance is unknown. We evaluated 87 sporadic
      isolates encountered in a clinical laboratory. Most isolates (62%) were
      respiratory; only 2 of 54 (4%) (both from patients with AIDS) were clinically
      significant. Among 33 nonrespiratory isolates, 20 of 33 (or 61%) were clinically
      significant. Clinical diseases included posttraumatic wound infections and
      catheter-related sepsis. Routine biochemical features included growth inhibition
      by 5% NaCl (100%), a smooth colony morphology (94%), positive 3-day arylsulfatase
      reaction (84%), no color or a light tan color on iron uptake (100%), and variable
      nitrate reduction (45%). Additional characteristics that helped to separate this
      group from M. chelonae and Mycobacterium abscessus were susceptibility to
      cephalothin (90%) and ciprofloxacin (100%), utilization of mannitol (94%) and
      citrate (83%) as carbon sources, and unique patterns of mycolic acid esters by
      high-performance liquid chromatography. This group was quite drug susceptible,
      with 100% of isolates inhibited by amikacin, imipenem, cefoxitin, cefmetazole,
      and the newer quinolones ciprofloxacin and ofloxacin. Three examples of this
      group, including a proposed type strain, have been deposited in the American Type
      Culture Collection.

PMID- 8308117
TI  - Coxsackievirus B1-based antibody-capture enzyme-linked immunosorbent assay for
      detection of immunoglobulin G (IgG), IgM, and IgA with broad specificity for
      enteroviruses.
AB  - An antibody-capture enzyme-linked immunosorbent assay (ELISA) with coxsackievirus
      B1 as the antigen was evaluated for detection of immunoglobulin G (IgG), IgM, and
      IgA antibodies and showed broad specificity for enteroviruses. In total, 116
      serum or cerebrospinal fluid samples from 62 patients were tested by ELISA and
      the complement fixation test (CFT). Additionally, 15 serum samples that contained
      poliovirus-specific IgM antibody were tested. Serum samples from 200 healthy
      blood donors were used for standardization of the assays. The sensitivity of the
      ELISA varied with time of serum sampling, with a relatively low sensitivity when
      serum was collected within 3 days after the onset of symptoms (23%; 5 of 22) but
      good sensitivity when serum was collected later (83%; 20 of 24). The sensitivity
      was better than that of the CFT. The ELISAs were broadly reactive as concluded
      from typing of virus isolates that were simultaneously obtained. The assay did,
      furthermore, detect antibody against poliovirus type 3. Sera that contained
      rheumatoid factor, antinuclear antibody, or cardiolipin antibody (by the Venereal
      Disease Research Laboratory test) did not react in this ELISA. Nonspecific
      reactivity did occur, however, in cases of infectious mononucleosis and in
      Mycoplasma pneumoniae infection. The enterovirus-specific ELISA is found to be
      simple to perform, more sensitive than the CFT, and far less laborious than the
      neutralization test.

PMID- 8308118
TI  - Demonstration of circulating pneumococcal immunoglobulin G immune complexes in
      patients with community-acquired pneumonia by means of an enzyme-linked
      immunosorbent assay.
AB  - An enzyme-linked immunosorbent assay was developed for quantitation of
      circulating immune complexes (CICs) containing specific antipneumococcal
      immunoglobulin G (IgG). These CICs were detected in 17 (85%) of 20 patients with
      bacteremic pneumococcal pneumonia, 4 (36.4%) of 11 patients with probable
      pneumococcal pneumonia, 3 (16.7%) of 18 patients with pneumonia of other
      (nonpneumococcal) etiology, and 13 (41.9%) of 31 patients with pneumonia of
      unknown etiology. There was no correlation between CICs and serum IgG antibody
      levels. Pneumococcal capsular antigen was demonstrated in dissociated CICs by
      latex agglutination.

PMID- 8308119
TI  - E test as susceptibility test and epidemiologic tool for evaluation of Neisseria
      meningitidis isolates.
AB  - The E test (AB Biodisk, Solna, Sweden), a new approach developed to test
      antimicrobial susceptibility, was compared with the agar dilution method for
      seven-drug antibiogram analysis of Neisseria meningitidis isolates. The overall E
      test quantitative accuracy (+/- 1 log2 dilution) was 93% compared with that of
      agar dilution testing. The E test was then used to perform the susceptibility
      tests on a 10-year sample of 102 N. meningitidis isolates, including 5 from a
      recent epidemic outbreak in the University of Iowa (Iowa City) community. The E
      test proved to be an efficient methodology for identifying common source clusters
      of meningococcal disease having resistance to rifampin or sulfonamides. Moreover,
      the data demonstrated a recent increase in penicillin MICs (MIC for 90% of
      strains, 0.094 microgram/ml) and an escalation of high-level resistance to
      trimethoprimsulfamethoxazole (33%) and rifampin (14%). The E test should be
      considered a simple and accurate susceptibility method for the emerging need to
      test meningococci and other pathogenic neisserias. Chocolate Mueller-Hinton agar
      was observed to provide the best support of growth and E-test MIC results that
      correlated well with results of the reference agar dilution method previously
      used for neisserias.

PMID- 8308120
TI  - Simultaneous detection of and differentiation between herpes simplex and
      varicella-zoster viruses with two fluorescent probes in the same test system.
AB  - Specimens from skin lesions were examined simultaneously for herpes simplex virus
      (HSV) and varicella-zoster virus (VZV) by direct specimen testing and shell vial
      culture in single-test systems. For direct testing, cells in a single specimen
      well were stained with a combination direct-indirect immunofluorescence stain by
      using two fluorescent tags. A total of 203 fresh specimens were tested in
      parallel. Of these, 100 specimens contained too few cells for the direct VZV
      comparison and 91 contained too few cells for the HSV comparison. After these
      specimens were eliminated, the sensitivities and specificities, respectively, of
      the dual direct test were 86.1 and 97.3% for HSV compared with single culture and
      92.2 and 100% for VZV compared with single direct testing. Shell vial monolayers
      in the combined cultures were stained for both viruses by the same method. A
      total of 305 fresh specimens were cultured in parallel by dual- and single
      culture methods. The sensitivities and specificities, respectively, of the
      combined culture compared with separate cultures were 100 and 98.4% for HSV and
      87.9 and 99.2% for VZV. The combined methods gave a performance comparable to
      those of single tests, required less specimen volume, and were less costly to
      perform.

PMID- 8308121
TI  - Detection of Mycobacterium tuberculosis in clinical specimens by polymerase chain
      reaction and Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test.
AB  - The polymerase chain reaction (PCR) using oligonucleotides based on the
      repetitive sequence (IS986) of Mycobacterium tuberculosis as a primer and the Gen
      Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD), which combines an
      M. tuberculosis rRNA amplification method with the hybridization protection assay
      format, were evaluated for detection of M. tuberculosis in clinical samples. The
      detection limits of these two assay systems based on nucleic acid amplification
      for cultured M. tuberculosis were less than 10 cells per reaction. A total of 135
      sputum specimens were examined by the two assay systems. The PCR and the MTD
      systems for detection of M. tuberculosis gave overall positivity rates of 84.2%
      (32 of 38) and 91.9% (34 of 37), respectively, as compared with 71.9% (23 of 32)
      by smear and 96.9% (31 of 32) by culture in the liquid medium MB-Check.
      Procedures for sample preparation used in the two methods were different.
      Although the sensitivities of the PCR and MTD appeared to be similar to that of
      culture with the MB-Check system, the two methods based on nucleic acid
      amplification should be very useful for rapid detection of M. tuberculosis
      infections without the long time required for culture of M. tuberculosis.

PMID- 8308122
TI  - Roseomonas, a new genus associated with bacteremia and other human infections.
AB  - In the 1980s, a pink bacterium different from species of the genus
      Methylobacterium was implicated in human infection. Using biochemical tests and
      DNA hybridization, we examined 42 strains of pink-pigmented, gram-negative
      bacteria that were not members of the genus Methylobacterium. The isolates
      included 6 strains each of CDC "pink coccoid" groups I, II, III, and IV; 10
      isolates from Gilardi's "unnamed taxon"; and 8 blood isolates from ill,
      debilitated, or immunosuppressed patients. The DNA hybridization studies
      supported the creation of six genomospecies encompassing the 42 strains.
      Reactions for esculin hydrolysis, glycerol oxidation, and D-mannose oxidation
      enabled separation of genomospecies 1 through 4. These tests, as well as
      motility, nitrate reduction, citrate utilization, and oxidation of L-arabinose, D
      galactose, and D-xylose, differentiated genomospecies 5 and 6 from each other and
      from genomospecies 1 through 4. These organisms were susceptible in vitro to the
      aminoglycosides, tetracycline, and imipenem and generally susceptible to the
      quinolones. We propose the new genus, Roseomonas, for these bacteria to include
      three named species, Roseomonas gilardii sp. nov., Roseomonas cervicalis sp.
      nov., and Roseomonas fauriae sp. nov., and three unnamed genomospecies.

PMID- 8308123
TI  - Methodological approaches to disinfection of human hepatitis B virus.
AB  - Three commercial disinfectants (two quaternary formulations and one phenolic)
      were tested against human hepatitis B virus (HHBV). The treated virus was assayed
      for infectivity by the chimpanzee assay and for morphological alteration by the
      Morphological Alteration and Disintegration Test. The same agents were tested
      against duck hepatitis B virus in a duck hepatocyte infectivity assay. It is
      apparent that human and duck hepatitis viruses were relatively susceptible to
      disinfection, becoming noninfectious after < or = 10 min of contact with the
      disinfectant. The Morphological Alteration and Disintegration Test accurately
      predicted activity in the two infectivity tests. The anti-human hepatitis B virus
      effect of the low-level quaternary ammonium germicides is a novel finding and
      suggest that members of the family Hepadnaviridae are relatively susceptible to
      chemical agents.

PMID- 8308125
TI  - Virological diagnosis of progressive multifocal leukoencephalopathy: detection of
      JC virus DNA in cerebrospinal fluid and brain tissue of AIDS patients.
AB  - Cerebrospinal fluid (CSF) from 12 AIDS patients with clinical signs consistent
      with progressive multifocal leukoencephalopathy (PML) was examined by the
      polymerase chain reaction (PCR) for the presence of JC virus (JCV). A specific
      JCV target sequence was amplified in the CSF from 9 of the 12 patients and also
      in brain tissue from all nine JCV-positive patients. The clinical course,
      neuroimaging features, and, in four cases, histopathology of brain tissue proved
      that the nine patients had PML. In the other three patients with central nervous
      system disorders, the JCV genome was undetectable by PCR and Southern blot
      analysis in CSF and brain tissue. The clinical course and neuroimaging features
      ruled out PML in these three patients. Five CSF samples and five brain tissue
      specimens from 10 PML-free AIDS patients with central nervous system disorders
      were all negative for the JCV genome by PCR and Southern blot analysis. These
      results show that detection of JCV in CSF by PCR is a good alternative to brain
      tissue studies for the virological diagnosis of PML in AIDS patients.

PMID- 8308124
TI  - Karyotyping of Cryptococcus neoformans as an epidemiological tool.
AB  - Karyotyping of Cryptococcus neoformans var. neoformans can be used as an
      epidemiological tool for C. neoformans infections. In this study of over 40
      isolates from both clinical and environmental sources, 90% had a unique
      chromosome banding by pulsed-field electrophoresis. There was no conserved
      pattern associated with body site of infection, geographical location of the
      isolate, or human immunodeficiency virus status. Karyotypes of individual
      isolates remained stable during both in vitro passage and in vivo infections.
      Karyotype was used to exclude the possibility of nosocomial spread of C.
      neoformans in one clinical situation and supported relapse in two other cases.
      Because of its variable sizes between isolates, karyotyping of C. neoformans is a
      convenient method for molecular identification of different strains.

PMID- 8308126
TI  - Bacterial flora of the sigmoid neovagina.
AB  - The bacterial microbiota of 15 sigmoid neovaginas, created in patients with
      congenital vaginal aplasia or male transsexualism, was studied. No specimen was
      sterile, and only normal inhabitants of the colon were cultured. The total counts
      of bacteria were lower than those reported for healthy sigmoid colons.

PMID- 8308127
TI  - Discrimination of epidemic and sporadic isolates of Arcobacter butzleri by
      polymerase chain reaction-mediated DNA fingerprinting.
AB  - DNA polymorphisms of Arcobacter butzleri outbreak-related strains and Arcobacter
      reference strains were determined by use of the polymerase chain reaction with
      primers aimed at repetitive sequences. The epidemiological relationship among 14
      outbreak-related strains was substantiated, as they showed virtually no genomic
      variations. Their DNA amplification patterns were, however, clearly different
      from those of all Arcobacter reference strains studied; each reference strain was
      characterized by a unique DNA fingerprint.

PMID- 8308128
TI  - Rapid method for presumptive identification of Corynebacterium jeikeium.
AB  - Corynebacterium jeikeium causes systemic infections, particularly in
      immunocompromised hosts. A minitube assay has been developed for the presumptive
      identification of C. jeikeium. With our rapid sucrose-urea test and conventional
      biochemical tests, sixty isolates of gram-positive, catalase-positive bacilli
      were identified in our laboratory. Results indicated that our assay has a
      sensitivity of 100% and a specificity of 90%.

PMID- 8308129
TI  - Prosthetic hip joint infection due to Campylobacter fetus.
AB  - A case of postoperative prosthetic hip joint infection due to Campylobacter fetus
      subsp. fetus is described. Difficulties in isolation and antimicrobial
      susceptibility testing of this organism are discussed.

PMID- 8308130
TI  - Rapid detection of Legionella species in bronchoalveolar lavage fluids with the
      EnviroAmp Legionella PCR amplification and detection kit.
AB  - A molecular assay based on a rapid DNA extraction protocol and the EnviroAmp
      Legionella Kits was used to detect Legionella species in bronchoalveolar fluid
      specimens. All Legionella strains isolated from tap water in hospitals could be
      detected distinctly. Both sensitivity and specificity were tested. In a
      prospective study, bronchoalveolar lavage fluids obtained from patients with
      atypical pneumonia were investigated. Three positive samples were detected with
      the molecular techniques and were subsequently confirmed by culture. Application
      of the system described may lead to safe and early diagnosis of Legionnaires'
      disease in patients with atypical pneumonia.

PMID- 8308131
TI  - Comparison of three buffers used in the formulation of buffered charcoal yeast
      extract medium.
AB  - Growth of Legionella spp. on buffered charcoal yeast extract medium supplemented
      with alpha-ketoglutarate and formulated with 3-(n-morpholino)propanesulfonic acid
      (MOPS), 3-(n-morpholino)-2-hydroxypropanesulfonic acid (MOPSO), or n-(2
      acetamido)-2-aminoethanesulfonic acid (ACES) buffer was similar. With three
      exceptions, growth was no different in buffered yeast extract broth supplemented
      with alpha-ketoglutarate and formulated with MOPS or ACES buffer.

PMID- 8308132
TI  - Value of whole-cell antigen extracts for serologic detection of Helicobacter
      pylori.
AB  - Whole-cell protein extracts of Helicobacter pylori strains were evaluated by
      enzyme-linked immunosorbent assay to detect immunoglobulin G antibody against H.
      pylori in 113 patients with upper gastrointestinal complaints. These antigen
      preparations were of value for detecting infection by H. pylori in patients with
      high antibody titers (> or = 12,800), whereas for patients with lower titers, the
      results were inconclusive.

PMID- 8308133
TI  - Molecular epidemiology and subgroup analysis of bovine group A rotaviruses
      associated with diarrhea in South African calves.
AB  - Rotavirus-positive specimens were recovered from 143 Afrikander calves on two
      farms in the northeastern Cape of South Africa during late 1988 and 1989. The
      rotavirus strains were analyzed by polyacrylamide gel electrophoresis of the RNA
      genome, and four rotavirus RNA electrophoretypes, each with a long profile, were
      identified. A distinct RNA profile was identified on the farms during 1988, but
      by early 1989, two patterns existed, one unique to each farm. Over the next 8
      months a new electrophoretic pattern emerged on one farm, whereas the pattern on
      the other farm remained unchanged. The rotavirus subgroup I antigen was detected
      in all specimens examined with subgroup-specific monoclonal antibodies. Non-group
      A rotaviruses were not identified by RNA genome analysis of 82 specimens from
      calves with diarrhea negative for group A rotaviruses by an enzyme-linked
      immunosorbent assay.

PMID- 8308134
TI  - Reliability of the E test for detection of ampicillin, vancomycin, and high-level
      aminoglycoside resistance in Enterococcus spp.
AB  - By comparison with agar dilution results, the E test was investigated for the
      ability to detect high-level aminoglycoside (gentamicin and streptomycin),
      ampicillin, and vancomycin resistance among strains representing six enterococcal
      species. For ampicillin and vancomycin, disk diffusion results also were
      obtained. No false high-level aminoglycoside resistance occurred, and no false
      gentamicin susceptibility was noted. With the high-range streptomycin E test
      (2,048 micrograms), 24% of the 38 resistant strains were falsely susceptible.
      However, these discordances could likely be reconciled by adjustments in
      incubation duration and by using broth microdilution rather than agar screen
      breakpoint criteria, or by using the lower-range (1,024-micrograms) strip. For
      ampicillin, category results obtained by E test and disk diffusion showed good
      agreement with agar dilution; E test MICs were generally comparable to agar
      dilution MICs. The E test was more sensitive than disk diffusion for detecting
      vancomycin-intermediate strains, but for these strains and those exhibiting low
      level vancomycin resistance (MIC, 32 to 128 micrograms/ml), disk diffusion and E
      test inhibition zones must be interpreted with caution. Given the reliability of
      E test for detecting resistance to anti-enterococcal agents, the decision to use
      this method should be based on convenience, cost, testing frequency, and
      satisfaction with currently used methods.

PMID- 8308135
TI  - New method for detection of Candida albicans in human blood by polymerase chain
      reaction.
AB  - We developed a new method for detection of Candida albicans cells in human blood
      by the polymerase chain reaction that amplifies a 125-bp region within a species
      specific, multiple-copy DNA fragment. In preparing template DNA from C. albicans
      containing blood, the addition of C. tropicalis cells, together with antibody
      which reacts with both cells, raised the sensitivity of detection of C. albicans
      to about 3 cells per 0.1 ml.

PMID- 8308136
TI  - Application of Lior biotyping by use of genetically identified Campylobacter
      strains.
AB  - We used the scheme of Lior to biotype 140 genetically identified Campylobacter
      strains. Our results confirmed previous studies and extended Lior biotyping to
      show that nine C. jejuni subsp. doylei strains (100%) were one biotype and nine
      C. jejuni subsp. jejuni nalidixic acid-resistant strains (100%) were C. jejuni
      biotype I or II. All C. jejuni subsp. jejuni hippurate-negative strains studied
      and 6 of 35 C. lari strains (17%) were grouped with C. coli biotypes. These
      findings may be useful in epidemiologic investigations.

PMID- 8308137
TI  - Diarrhea in U.S. troops deployed to Thailand.
AB  - Ninety-five (28%) of 333 U.S. military personnel deployed to Ubonratchathani,
      Thailand, for 1 month in February 1993 developed diarrhea. Campylobacter jejuni
      was identified in 6 (25%), attaching and effacing Escherichia coli was identified
      in 3 (13%), nontyphoidal Salmonella spp. were identified in 2 (8%), and rotavirus
      was identified in 1 (4%) of 24 persons who had diarrhea and submitted specimens.

PMID- 8308138
TI  - Actinomyces pyogenes-like bacteria.

PMID- 8308139
TI  - Monitoring during supratentorial surgery.
AB  - Electroneurophysiological monitoring is employed during various supratentorial
      surgical procedures. EEG and evoked potential monitoring are used to detect and
      to facilitate the timely correction of cerebral ischemia during carotid
      endarterectomy and aneurysm surgery. Direct cortical recording and stimulation is
      used to identify areas or cortex that would be likely to produce clinical
      deficits if removed. Electrocorticography is used to identify epileptogenic
      cortex intraoperatively during surgical treatment of epilepsy.

PMID- 8308140
TI  - Posterior fossa intraoperative monitoring.
AB  - Monitoring of brainstem structures is requested of the neurophysiologist for both
      intra-axial and extra-axial surgeries of the posterior fossa. A variety of
      techniques to include upper extremities somatosensory evoked potentials, short
      latency auditory evoked potentials, spontaneous and evoked electromyographic
      activity, and recordings from the cochlea and the eighth nerve are available. The
      indication, implementation, and interpretation of each of these modalities are
      delineated. The efficacy and utility of these techniques are also discussed.

PMID- 8308141
TI  - Up and down the spinal cord: intraoperative monitoring of sensory and motor
      spinal cord pathways.
AB  - Monitoring of spinal cord function during certain orthopedic and neurosurgical
      procedures is done to reduce the likelihood of neurologic complications. This
      article is based on intraoperative experiences gained at Duke University Medical
      Center since 1978. Both ascending sensory (up) and descending motor (down) data
      can be evaluated to assist in improved patient outcomes. Refinements in technique
      and better understanding of the neural generators of evoked potentials obligate
      the components to have improved sensitivity and specificity of spinal
      intraoperative monitoring. An additional improvement has been the intraoperative
      use of motor evoked potentials. This discussion deals with a description of
      specific responses obtained following lower-limb mixed nerve stimulation in terms
      of neural generation, influences of rate and intensity, and anesthetic effects.
      The techniques and advantages of bipolar epidural recording and stimulation are
      discussed. Motor tract stimulation via the same epidural electrodes used for
      recording of sensory components is described. Case reports are presented to
      emphasize major points.

PMID- 8308142
TI  - Intraoperative electroencephalography.
AB  - EEG is useful in several operating room procedures. It has come to be a standard
      part of monitoring patients during carotid endarterectomy. Monitoring for
      cerebral hypoperfusion or emboli can also be done in cardiac surgery or other
      similar settings. For carotid endarterectomy, studies in humans suggest that the
      risk of stroke can be reduced 10-fold by selective vascular shunting based on
      major EEG changes compared to no shunting. EEG can be recorded from exposed
      cerebral cortex, a technique referred to as electrocorticography. Such recordings
      can help identify damaged cortex, separating it from normal functioning cortex.
      This can influence the extent of neurosurgical cortical resections. Although much
      of the technology in the operating room is based on that common in routine EEG
      testing, some differences exist and are discussed here. The well-trained
      electroencephalographer should find recording and interpreting EEG in the
      surgical setting to be a natural extension of routine EEG.

PMID- 8308143
TI  - Continuous EEG and evoked potential monitoring in the neuroscience intensive care
      unit.
AB  - As with other methods long used in intensive care units (ICU) and operating rooms
      (OR), the goal of neuroscience ICU continuous EEG (NICU-CEEG) and evoked
      potential (NICU-EP) monitoring is to extend our powers of observation to detect
      abnormalities at a reversible stage. EEG is an appropriate monitoring tool
      because it is linked to cerebral metabolism, is sensitive to ischemia and
      hypoxemia, correlates with cerebral topography, detects neuronal dysfunction at a
      reversible stage, and is the best method for detecting seizure activity. When
      applied systematically, it can impact medical decision-making in 81% of monitored
      patients. It is useful in monitoring precarious cerebral perfusion at the
      bedside, and it has revealed that nonconvulsive seizures, undetectable otherwise,
      occur in 34% of NICU patients. In convulsive status epilepticus, NICU-CEEG can
      help avoid undertreatment and overtreatment. In comatose patients, it can provide
      useful prognostic information as well as detect potentially treatable causes.
      Traditional impediments to its application are yielding to technological advances
      and educational efforts. Real-time digitized EEG in particular has been a major
      advance. Within limits, somatosensory evoked potential monitoring (ICU-SEP) is
      useful in the prognosis of coma, but it is less helpful in monitoring focal
      cerebral ischemia. Brainstem auditory evoked potential monitoring has a
      relatively restricted role in the NICU but is helpful in distinguishing
      structural from nonstructural causes of coma and can supplement ICU-SEP in
      predicting outcome.

PMID- 8308144
TI  - History and evolution of electroencephalographic instruments and techniques.

PMID- 8308145
TI  - Facilitation of motor evoked potentials from magnetic brain stimulation in man: a
      comparative study of different target muscles.
AB  - The influence of tonic muscle contraction and stimulus intensity on compound
      muscle action potentials (CMAPs) elicited by magnetic brain stimulation was
      studied in the biceps brachii (34 subjects), the abductor digiti minimi (11
      subjects), the anterior tibial muscle (12 subjects), and the soleus muscle (5
      subjects). The muscles were examined at rest and with various degrees of
      background contraction of up to 60% of maximum force. Stimulus intensity was set
      at threshold (TSI) or 20% above threshold (1.2 TSI), and in one series
      additionally at 50% above threshold (1.5 TSI). The effect of voluntary background
      contraction on CMAP onset latency was similar in the four muscles tested: the
      latencies shortened by approximately 3 ms when the muscle changed from the
      relaxed to the contracted state of the 10% of maximum force. An additional
      increase in the background contraction up to 60% of maximum force induced only
      few, if any, additional decreases in latency. The uniformity of the latency shift
      in distal and proximal muscles conflicts with the idea of recruitment of larger
      and rapidly conducting motoneurons being the cause, since this hypothesis would
      imply a more pronounced latency reduction in distal than in proximal muscles. The
      shorter latency during voluntary contraction is more likely due to an enhanced
      synaptic efficacy at spinal level. Since the motoneurons are brought into an
      increased state of activity during contraction, they require less temporal
      summation to reach firing threshold and thus discharge earlier. The CMAP
      amplitudes of the different muscles were more distinctly affected by voluntary
      background contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308146
TI  - Equivalent electrical source analysis of pain-related somatosensory evoked
      potentials elicited by a CO2 laser.
AB  - The purpose of this study was to localize possible neural sources of pain-related
      cortical evoked potentials. A brain electrical source analysis was performed on
      late somatosensory evoked potential data (500-ms window was analyzed) elicited by
      short heat pulses produced by a CO2 laser. These stimuli activate pain and
      temperature pathways. The first, fairly small, negative response can be recorded
      on the scalp about 160 ms from the stimulus (N1 component). The major negativity
      on the scalp has its peak about 240 ms from the stimulus and is followed by a
      positivity (N2 and P2 components). A four-dipole model was developed using data
      following left-hand stimulation. Spatiotemporal source analysis suggested that
      the N1 component could be generated by contralateral activity in both primary and
      secondary somatosensory cortices and that N2 could be generated by bilateral
      activity mainly in secondary somatosensory cortices. A deep dipole in the midline
      was active during the time range of the negative potentials and seemed to be
      mostly responsible for the P2 component. This dipole was located too frontally to
      be thalamic, but it corresponded well to the location of the anterior cingulate
      gyrus. The model also yielded good fits for right-hand and left-foot stimulation
      data and, in addition, another set of left-hand data obtained with different
      electrode spacing in a different group of subjects (residual variances from 2.8%
      to 3.3%). The model explaining data sets from different body part stimulations
      varied very little, except with respect to the location of the dipole
      representing the activity of the primary somatosensory area.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8308147
TI  - Alfentanil-induced epileptiform activity in patients with partial epilepsy.
AB  - We performed a retrospective study investigating the effect of alfentanil
      hydrochloride on electrocorticography (ECoG) in 23 patients with intractable
      nonlesional partial epilepsy undergoing anterior temporal lobectomies at this
      institution. Alfentanil is a short-acting, parenteral, opioid analgesic with a
      rapid onset of action. Opioid drugs have the potential to induce hippocampal
      electrographic seizures. Pre-excision ECoG was obtained before and after the
      administration of 50 micrograms/kg of alfentanil. ECoG was performed using
      subdural strips placed on the lateral temporal surface and in the suprasylvian
      region and monopolar depth electrodes implanted into the amygdala and
      hippocampus. The surgically excised temporal lobes revealed cortical gliosis and
      varying degrees of hippocampal neuronal loss in all patients. A quantitative
      assessment of the effect of alfentanil on the ECoG was performed by measuring the
      frequency of interictal spikes. There was a significant increase in the mesial
      temporal lobe mean spike frequency after the administration of alfentanil (p <
      0.001). One patient had an alfentanil-induced mesial temporal lobe electrographic
      seizure. Alfentanil did not have a significant effect on spike activity in the
      suprasylvian region (p = 0.500). Further studies will be necessary to determine
      the specificity of alfentanil activation in patients with partial seizures of
      temporal lobe origin.

PMID- 8308148
TI  - Technology and equipment review. Intraoperative monitoring equipment.

PMID- 8308149
TI  - Responses to the views and commentary on "Standard specification for transferring
      digital neurophysiological data between independent computer systems" (ASTM E1467
      92) (J Clin Neurophysiol 1993;10:397)

PMID- 8308150
TI  - Responses to the views and commentary on "Standard specification for transferring
      digital neurophysiological data between independent computer systems" (ASTM E1467
      92) (J Clin Neurophysiol 1993; 10:397)

PMID- 8308151
TI  - Responses to the views and commentary on "Standard specification for transferring
      digital neurophysiological data between independent computer systems" (ASTM E1467
      92) (J Clin Neurophysiol 1993; 10:397)

PMID- 8308152
TI  - Responses to the views and commentary on "Standard specification for transferring
      digital neurophysiological data between independent computer systems" (ASTM E1467
      92) (J Clin Neurophysiol 1993; 10:397)

PMID- 8308153
TI  - Responses to the views and commentary on "Standard specification for transferring
      digital neurophysiological data between independent computer systems" (ASTM E1467
      92) (J Clin Neurophysiol 1993; 10:397)

PMID- 8308154
TI  - Responses to the views and commentary on "Standard specification for transferring
      digital neurophysiological data between independent computer systems" (ASTM E1467
      92) (J Clin Neurophysiol 1993; 10:397)

PMID- 8308155
TI  - Responses to the views and commentary on "Standard specification for transferring
      digital neurophysiological data between independent computer systems" (ASTM E1467
      92) (J Clin Neurophysiol 1993; 10:397)

PMID- 8308156
TI  - Responses to the views and commentary on "Standard specification for transferring
      digital neurophysiological data between independent computer systems" (ASTM E1467
      92) (J Clin Neurophysiol 1993; 10:397)

PMID- 8308157
TI  - Responses to the views and commentary on "Standard specification for transferring
      digital neurophysiological data between independent computer systems" (ASTM E1467
      92) (J Clin Neurophysiol 1993; 10:397)

PMID- 8308158
TI  - Responses to the views and commentary on "Standard specification for transferring
      digital neurophysiological data between independent computer systems" (ASTM E1467
      92) (J Clin Neurophysiol 1993; 10:397)

PMID- 8308159
TI  - Mushroom spring for minor tooth movement.

PMID- 8308160
TI  - Simplified Quad Helix construction.

PMID- 8308161
TI  - 1993 JCO orthodontic practice study. Part 1. Trends.

PMID- 8308162
TI  - Rapid Class II correction with a headgear-expander.

PMID- 8308163
TI  - A practical biteplane for use with fixed appliances.

PMID- 8308164
TI  - Generalized idiopathic external root resorption.

PMID- 8308165
TI  - Organization of the proximal, orbital segment of the infraorbital nerve at
      multiple intervals after axotomy at birth: a quantitative electron microscopic
      study in rat.
AB  - Although much is known of the central consequences of infraorbital nerve (ION)
      transection at birth, little is known about the effects of this lesion on the
      organization of the ION itself. To advance our understanding of how
      deafferentation alters the developing trigeminal neuraxis, 19 newborn rats were
      subjected to left ION section and perfused 1, 2, 4, 7, 17, or 90 days later. Left
      IONs were removed in the orbit proximal to the nerve injury site, and axon
      numbers, types, and fasciculation patterns were assessed with light and electron
      microscopic methods. Complete axon counts demonstrated that the axotomized ION
      contained an average (+/- SD) of 13,945 +/- 10,335, 14,112 +/- 3,501, 16,531 +/-
      1,904, 9,045 +/- 1,465, 7,018 +/- 4,212, and 8,672 +/- 1,030 axons at the above
      listed ages, respectively. These values are well below the 33,059 axons in the
      normal adult ION (Jacquin et al. [1984] Brain Res. 290:131-135) and the 42,219
      axons in the newborn ION (Renehan and Rhoades [1984] Brain Res. 322:369-373). The
      axotomized ION also contained lower than normal percentages of myelinated axons
      (26.7% +/- 6.3% on postnatal day 90 vs. 59.7% +/- 6.2% in normal adults).
      Unmyelinated fibers constituted the vast majority of the remaining fiber types;
      degenerating fibers never accounted for > 1.6% of all the axons. The number of
      fascicles making up the axotomized ION overlapped significantly with those found
      in the normal newborn and adult ION. We conclude that 1) extensive, though
      variable, axon elimination occurs proximally within one day of the lesion; 2) the
      74% reduction in fiber number seen at 90 days is not reliably achieved until
      postnatal day 7; 3) the higher than normal proportion of unmyelinated axons in
      the injured ION may underly many of the known effects of neonatal ION injury on
      the developing whisker-barrel neuraxis; 4) gross changes in ION fasciculation
      patterns are not prerequisite to injury-induced pattern alterations in the
      developing trigeminal system.

PMID- 8308166
TI  - Segregation of direction selective neurons and synaptic organization of
      inhibitory intranuclear connections in the medial terminal nucleus of the rat: an
      electrophysiological and immunoelectron microscopical study.
AB  - A combined electrophysiological and morphological investigation of the medial
      terminal nucleus (MTN) in the rat was undertaken, aimed at a better understanding
      of the relationship between structure and function in this nucleus. The locations
      of upward and downward direction selective units in the MTN were documented with
      extracellular electrophysiological recording. By means of tracer experiments,
      with Phaseolus vulgaris-leucoagglutinin, biocytin, and cholera toxin subunit B
      horseradish peroxidase, the internal connections of the MTN, its retinal
      afferents, and the projection neurons to the inferior olive were visualized.
      Terminals originating from the retina and from internal connections were
      characterized at the ultrastructural level. Their termination pattern on cells in
      the MTN, including identified inferior olive projection neurons, were determined.
      Additionally, postembedding GABA immunocytochemistry was performed to identify
      GABAergic elements. From reconstructions of the positions of
      electrophysiologically recorded units in the MTN, a local segregation between
      upward and downward direction selective units was revealed. Upward direction
      selective units were found in the dorsal part and ventromedially, whereas
      downward direction selective units were found ventral and laterally in the MTN.
      The MTN receives optic fibers via two separate routes which, based on their
      trajectory, presumably terminate in different parts of the MTN: the inferior
      fascicle of the accessory optic tract in the dorsal part, and the posterior fiber
      bundle of the superior fascicle in the ventral part of the MTN. A correspondence
      has been found between the segregation of direction selective units and the areas
      in the MTN where the retinal fibers from the two pathways distribute. It is,
      therefore, proposed that the inferior fasciculus conveys upward direction
      selectivity and the posterior fiber bundle downward direction selectivity, and
      that the two fiber bundles terminate segregated in the MTN. After anterograde
      tracing from the eye, retinal terminals were found evenly distributed throughout
      the MTN. They are characterized as GABA negative R-type terminals. After
      retrograde tracing from the inferior olive, identified MTN-inferior olive
      projection neurons were found in the dorsal MTN and medially in the ventral MTN.
      Their location in the MTN suggests that MTN-inferior olive projection neurons are
      upward direction selective. MTN-inferior olive projection neurons are large non
      GABAergic cells, with a variable form. A majority of both F- and R-type terminals
      were found to make synaptic contacts on the dendrites of MTN cells. MTN-inferior
      olive projection neurons did not differ from other neurons in this respect.

PMID- 8308167
TI  - Transient cortical pathways in the pyramidal tract of the neonatal ferret.
AB  - Anterograde transport of wheat germ agglutinin conjugated to horseradish
      peroxidase (WGA-HRP) was used to study transient axons from the visual cortex in
      the pyramidal tract. Injections at birth restricted to the visual cortex labeled
      axons in the vicinity of the pontine nuclei. Two to eight days after birth, axons
      from the occipital cortex were found posterior to the pontine nucleus, their
      caudalmost stable target. Transient corticospinal axons from the presumptive
      primary visual cortex did not grow caudal to the pyramidal decussation.
      Innervation of more distal targets preceded innervation of proximal targets.
      Innervation of the pontine nucleus is initiated around 68 hours after birth, when
      the transient extension in the medullary pyramidal tract has attained its maximum
      caudal extent. Innervation of the superior colliculus begins 9 days after birth.
      Retrograde tracers were used to follow the developmental changes in the cortical
      distribution of the parent neurons giving rise to axons in the pyramidal tract.
      In the adult, labeled neurons following injection of retrograde tracer in the
      pyramidal tract occupied less than a third of the neocortex and were centred on
      the anterior part of the coronal and spleniocruciate gyri. In the immature brain,
      labeled neurons covered more than two-thirds of the neocortex. Areal density
      measurements in the neonate showed that peak labeling was centred in the anterior
      coronal and spleniocruciate gyri, where corticospinal cells in the adult are
      located. There was a marked rostral-caudal gradient so that labeled neurons were
      very scarce towards the occipital pole. These results, showing transient
      neocortical axons in the pyramidal tract in a carnivore, suggest that this may be
      a common feature of mammalian development. The finding that the adult pattern of
      corticospinal projections does not emerge from a uniform distribution is
      discussed with respect to the areal specification of cortical connectivity.

PMID- 8308168
TI  - Recovery of original nerve supply after hypoglossal-facial anastomosis causes
      permanent motor hyperinnervation of the whisker-pad muscles in the rat.
AB  - Hypoglossal-facial anastomosis (HFA), used in humans for the treatment of facial
      palsy, was experimentally performed in adult female Wistar rats. The time course
      of facial reinnervation and the extent of the new motor nerve supply of the
      vibrissal muscles that develops after HFA were estimated by counting all
      motoneurons in the brainstem labeled by injection of horseradish peroxidase (HRP)
      into the whisker pad; muscle innervation by motor endplates was not studied. In
      untreated animals, HRP injection labels 1,254 +/- 54 (mean +/- S.D.; n = 6)
      motoneurons, localized exclusively in the lateral subdivision of the facial
      nucleus. Immediately following HFA, this number drops to zero. The first HRP
      labeled motoneurons appear in the hypoglossal nucleus at 28 days postoperation
      (dpo) and at 56 dpo their number reaches 1,096 +/- 48. Unexpectedly, the facial
      nerve, whose proximal stump has been left as blind end during surgery,
      additionally sends axons to the facial periphery. This resprouting is first
      detected at 42 dpo with HRP-marked neurons throughout the facial nucleus lacking
      somatotopic organization. The number of these labeled neurons also rises with
      time, and at 56 dpo, a total of 1,797 +/- 142 facial and hypoglossal motoneurons,
      that is, 43% more motoneurons than in normal animals, supplies the whisker pad.
      This hyperinnervation, that is, the projection of more motoneurons into the
      target muscle than under normal conditions--further increases to 1,978 +/- 92
      motoneurons at 224 dpo and may provide a new animal model for studying the
      competitive relationships between motoneurons in their search for peripheral
      targets.

PMID- 8308169
TI  - Descending projections of the songbird nucleus robustus archistriatalis.
AB  - The descending, efferent projections of nucleus robustus archistriatalis were
      investigated in male zebra finches and greenfinches with injections of either
      biotinylated dextran amine or cholera toxin B-chain conjugated to horseradish
      peroxidase. The results show that in addition to the well-known projections to
      the tracheosyringeal motor nucleus and the dorsomedial nucleus of the
      intercollicular complex, there are other projections of comparable density to the
      ipsilateral nucleus ambiguus and nucleus retroambigualis. Within nucleus
      ambiguus, robustus axons terminate in close proximity to laryngeal motoneurons
      which were retrogradely labelled in the same bird by injections of cholera B
      chain into the laryngeal muscles; and within nucleus retroambigualis robustus
      axons terminate in relation to bulbospinal neurons previously shown to project to
      regions of spinal cord containing motoneurons innervating abdominal expiratory
      muscles (J.M. Wild, Brain Res. 606:119-124, 1993). These projections of nucleus
      robustus thus seem well placed to coordinate syringeal, laryngeal, and expiratory
      muscle activity during vocalization. Other relatively sparse, but distinct,
      projections of nucleus robustus were found to nucleus dorsolateralis anterior
      thalami, pars medialis, to a narrow region between the superior olivary nucleus
      and the spinal lemniscus, and to the rostral ventrolateral medulla. Neurons in
      these last two locations were retrogradely labelled bilaterally following
      injections of cholera B-chain into nucleus retroambigualis of one side. Together
      with sparse contralateral projections of nucleus robustus to all brainstem
      targets receiving ipsilateral projections, potential pathways are thus identified
      by which the respiratory-vocal activity controlled by one side of the lower
      medulla can be influenced by the nucleus robustus of either side, thereby
      possibly bringing about bilateral coordination of respiratory-vocal output.

PMID- 8308170
TI  - Retinal ganglion cells within the foveola of New World (Saimiri sciureus) and Old
      World (Macaca fascicularis) monkeys.
AB  - The morphology and distribution of retinal ganglion cells within the foveola of
      New World (Saimiri sciureus) and Old World (Macaca fascicularis) monkeys labeled
      as a result of horseradish peroxidase injections into the dorsal lateral
      geniculate nucleus were studied. The results indicate that monkey's foveola
      normally contains significant numbers of retinal ganglion cells. Most of these
      project ipsilaterally. Cells within the foveola are larger than other cells in
      monkey central retina; their dendritic fields are up to 50 times larger in area
      than those of cells in the foveal slope. The dendritic fields of the ganglion
      cells within the foveola cover at least 70-100% of its area. Among ganglion cells
      within the foveola (as in most ganglion cells), there was a strong tendency for
      the axon and dendritic tree to arise from opposite poles of the soma. The axon
      dendrite axes of ganglion cells within the foveola did not show a consistent
      pattern. In contrast, the axes of ganglion cells in the transition zone between
      the foveola and the foveal slope were directed tangentially to the circumference
      of the fovea. The dendritic coverage of the foveola by retinal ganglion cells
      suggests functional significance and provides a possible neural basis for 2-3
      degrees of bilateral representation of the fovea within the central visual
      pathways. Alternatively, or in addition, these cells may be "remnants of
      foveation" and provide insight into the developmental processes that mediate the
      development of the fovea.

PMID- 8308171
TI  - The patterns of afferent innervation of the core and shell in the "accumbens"
      part of the rat ventral striatum: immunohistochemical detection of retrogradely
      transported fluoro-gold.
AB  - Recent data have emphasized the neurochemically distinct nature of subterritories
      in the accumbens part of the rat ventral striatum termed the core, shell, and
      rostral pole. In order to gain a more comprehensive understanding of how
      afferents are distributed relative to these subterritories, immunohistochemical
      detection of retrogradely transported Fluoro-Gold was carried out following
      iontophoretic injections intended to involve selectively one of the
      subterritories. The data revealed that a number of cortical afferents of the
      medial shell and core originate in separate areas, i.e., the dorsal peduncular,
      infralimbic, and posterior piriform cortices (to medial shell) and the dorsal
      prelimbic, anterior agranular insular, anterior cingulate, and perirhinal
      cortices (to core). The lateral shell and rostral pole are innervated by cortical
      structures that also project either to the medial shell or core. The orbital,
      posterior agranular insular, and entorhinal cortices, hippocampus, and basal
      amygdala were observed to innervate the accumbens in a topographic manner.
      Following core injections, strong bilateral cortical labeling was observed. Few
      labeled cortical cells were observed contralaterally following injections in the
      medial shell. Intermediate numbers of labeled neurons were observed in
      contralateral cortices following lateral shell injections. Robust subcortical
      labeling in a variety of structures in the ventral forebrain, lateral
      hypothalamus, deep temporal lobe, and brainstem was observed after shell
      injections, particularly those that involved the caudal dorsomedial extremity of
      the shell, i.e., its "septal pole." Selective ipsilateral labeling of subcortical
      structures in the basal ganglia circuitry was observed following injections in
      the core and, to a lesser extent, lateral shell. It was concluded that a number
      of afferent systems exhibit varying degrees of segregation with respect to the
      accumbal subterritories.

PMID- 8308172
TI  - Spatial and temporal expression identify dromyosuppressin as a brain-gut peptide
      in Drosophila melanogaster.
AB  - The Drosophila dromyosuppressin peptide (TDVDHVFLRFamide) is a member of a family
      of peptides containing the common C-terminal sequence-RFamide. Dromyosuppressin
      shares a high degree of sequence homology with leucomyosuppressin isolated from
      cockroach (pEDVDHVFLRFamide) and identity with neomyosuppressin isolated from
      fleshfly. By means of sequence-specific antisera, the cellular expression pattern
      of dromyosuppressin immunoreactive material was determined for all stages of
      Drosophila development. Dromyosuppressin immunoreactivity first appears in two
      cells of the medial protocerebrum in embryos. The larval stage is characterized
      by an increase in the number of dromyosuppressin immunoreactive cells in the
      brain and the first appearance of cellular expression in the ventral ganglion.
      Immunoreactive fibers extend from the medial protocerebrum cells into the ventral
      ganglion. Relative to the larval stage, the pupal and adult stages are marked by
      an increase in the number of immunoreactive cells in the central nervous system
      and an increase in the arborization of immunoreactive fibers extending from these
      cells. Immunoreactivity is present in larvae in two cells near the anus; in the
      adult gut, expression is observed in two cells in the rectum and immunoreactive
      fibers in the crop that appear to extend from the central nervous system. In
      general, the number of cells containing dromyosuppressin immunoreactive material
      increases throughout Drosophila development. However, expression in three cells
      is restricted to specific developmental periods. These data identify
      dromyosuppressin as a brain-gut peptide regulated at both a cellular and
      developmental level.

PMID- 8308173
TI  - Survey of the morphology of macaque retinal ganglion cells that project to the
      pretectum, superior colliculus, and parvicellular laminae of the lateral
      geniculate nucleus.
AB  - In common with other vertebrates, the primate retina contains a number of
      different ganglion cell types that project to different regions in the brain. We
      wanted to determine how the different ganglion cell types, distinguished
      morphologically, mapped to these regions of the brain. We injected a fluorescent
      dye into one of three regions of a macaque brain: the superior colliculus (SC),
      the pretectal region, and the parvicellular laminae of the lateral geniculate
      nucleus. By means of an in vitro preparation, the retrogradely labelled ganglion
      cells were intracellularly injected with horseradish peroxidase, so as to reveal
      their dendritic morphology. When the dendritic-field diameters of the injected
      cells were plotted against retinal eccentricity, each of the three regions was
      found to receive input from a distinctive population of cells. The pretectal
      projection was dominated by cells with large dendritic fields. The SC projection
      was composed of a number of distinct types, with smaller dendritic fields.
      Parasol cells project to SC but are extremely rare. In addition to midget
      ganglion cells, the parvicellular laminae receive inputs from at least two
      additional groups. Parvicellular bistratified (PB) cells have bistratified
      dendritic fields, slightly larger than those of parasol cells. Parvicellular
      giant (PG) cells have dendritic-field diameters larger than that of any parasol
      cell, ranging from 250 microns to greater than 850 microns--the largest of any
      primate ganglion cells. In contrast to the retinal projections of the cat, in
      which a specific ganglion cell type can project to different regions of the
      brain, each of the regions in this survey appears to receive inputs from its own
      distinct group of ganglion cells.

PMID- 8308174
TI  - Prenatal development of the retinohypothalamic pathway and the suprachiasmatic
      nucleus in the sheep.
AB  - Circadian rhythms are present during fetal life in several mammalian species. To
      characterize the ontogeny of the neural mechanisms that account for circadian
      rhythmicity in a precocious species, we studied the prenatal development of the
      retinohypothalamic pathway in lambs (gestation period of 147 days), using
      horseradish peroxidase and wheat germ agglutinin as anterograde tracers. The
      suprachiasmatic nucleus was present as early as embryonic day 52 (E52). After
      E58, the suprachiasmatic nucleus reached its full number of neurons, estimated by
      the disector method in about 160,000 cells per nucleus at E62. The
      retinohypothalamic axons invaded the suprachiasmatic nucleus from E58, while
      neuroblasts were still migrating to the nucleus. At E62, there was a strong
      retinal projection that evolved until E121, when the retinal afferents
      established their definitive pattern of distribution in the ventral and central
      regions of the suprachiasmatic nucleus, and adjacent hypothalamic structures. The
      development of the retinohypothalamic pathway was delayed by about a week
      relative to the innervation of other subcortical visual centers. The present
      findings demonstrated an early prenatal development of the visual pathways in
      lambs, including the retinohypothalamic pathway, suggesting that the mechanisms
      for the visual entrainment of circadian rhythms in lambs may be functioning
      several weeks before birth.

PMID- 8308175
TI  - Atopic children with cystic fibrosis have increased urinary leukotriene E4
      concentrations and more severe pulmonary disease.
AB  - BACKGROUND: We investigated the hypothesis that cysteinyl leukotriene (LT)
      production is altered in atopic patients with cystic fibrosis (CF). METHODS:
      Urinary LTE4 was measured in two groups of children with CF: atopic (ACF group, n
      = 22) and nonatopic (NACF group, n = 13); and in two groups of unaffected
      children, those with atopic asthma (AA group, n = 11) and nonatopic normal
      control subjects (NN group, n = 12). RESULTS: Atopic groups excreted
      significantly more urinary LTE4 (geometric means [95% confidence intervals] in
      picomoles per millimole creatinine), ACF group: 104 (73-147) and AA group: 195
      (136-282) compared with NACF group: 19 (9-39) and NN group: 27 (15-48). The ACF
      group had significantly more airflow obstruction than the NACF group, with forced
      expiratory volume in 1 second (percent predicted, mean +/- SD) in ACF: 58 +/- 21
      versus NACF: 81 +/- 23, and forced vital capacity (percent predicted, mean +/-
      SD) 72 +/- 17 versus 87 +/- 23, respectively. There were significant correlations
      between the degree of airflow obstruction, bronchodilator responsiveness, and
      urinary LTE4 concentration within the entire CF group. We used multiple
      regression analysis to assess the respective influence of age, atopy,
      sensitization to Aspergillus fumigatus, and colonization with Pseudomonas
      aeruginosa on urinary LTE4 concentration. The atopic state was the only
      significant variable associated with urinary LTE4 production in subjects with CF.
      CONCLUSIONS: The similarities in urinary LTE4 between ACF and AA groups suggest
      that the atopic state is the prime determinant of urinary LTE4 excretion.
      Enhanced cysteinyl LT production associated with atopy in CF may increase the
      severity of pulmonary disease.

PMID- 8308176
TI  - IgE produces monocyte superoxide anion release: correlation with CD23 expression.
      Comparison of patients with asthma, patients with rhinitis, and normal subjects.
AB  - Allergic inflammation involves many different cell types among which mononuclear
      cells, such as macrophages and monocytes, play an important role. These cells
      release numerous chemical mediators, including superoxide anion (O2.-). We
      evaluated the capacity of atopic serum to stimulate peripheral blood monocyte O2.
      release. Thirteen untreated allergic patients (seven with asthma and six with
      rhinitis), and five nonallergic control subjects were studied. O2.- was measured
      in a photon-counting camera with Lucigenin-enhanced (Sigma Chemical Co., St.
      Louis, Mo.) chemiluminescence. Results were expressed (mean +/- SEM) in relation
      to basal values (peak/basal chemiluminescence values). Spontaneous production of
      O2.- was greater in allergic patients. Moreover, atopic serum stimulated O2.-
      production of blood monocytes in all subjects, but this was greater in subjects
      with allergic asthma than in subjects with allergic rhinitis and normal subjects.
      Anti-IgE immunoadsorption of atopic serum completely abrogated this effect, which
      was restored by the IgE-rich eluted fraction. IgE-induced O2.- release decreased
      as adherence duration increased and was correlated with surface CD23 expression.
      These results indicate that monocytes from allergic patients are in an activated
      state and that binding of IgE to their receptors generates O2.-, possibly by
      direct activation of blood monocyte reduced nicotinamide adenine dinucleotide
      phosphate oxidase.

PMID- 8308177
TI  - Immunologic analysis of anaphylaxis to protamine component in neutral protamine
      Hagedorn human insulin.
AB  - We report the clinical and immunologic analysis of two patients with diabetes who
      had anaphylaxis to neutral protamine Hagedorn (NPH) human insulin in the absence
      of allergy to regular insulin. A 36-year-old woman without a recent history of
      local insulin reactions or interruption of insulin therapy experienced
      anaphylaxis within 15 minutes of her usual morning dose of subcutaneously
      administered NPH human insulin. A 62-year-old man with a history of generalized
      reactions to NPH human insulin and of anaphylaxis to intravenously administered
      protamine had generalized urticaria after injection of NPH human insulin. Both
      patients subsequently tolerated Lente human insulin. Skin test results in both
      patients were negative to regular and Lente insulin preparations but positive to
      NPH insulin and to protamine at concentrations tested. In vitro assays
      demonstrated that both patients had markedly elevated serum levels of IgE and IgG
      to protamine, but not to regular human insulin, and that their IgE antibodies to
      protamine recognized protamine antigenic determinants in NPH human insulin. We
      conclude that the anaphylactic reactions to NPH insulin in our patients were
      mediated by IgE to protamine, which should be a pathogenetic consideration in the
      evaluation of immediate-type reactions to protamine-containing insulins.

PMID- 8308178
TI  - Is reactive airways dysfunction syndrome a variant of occupational asthma?
AB  - BACKGROUND: Reactive airways dysfunction syndrome (RADS) or irritant-induced
      asthma is a syndrome that leaves subjects with asthma-like symptoms after one or
      more exposures to a high concentration of an irritant substance. The degree of
      reversibility of airway obstruction in subjects with RADS is nevertheless
      unknown, as is the degree of associated lesions at the airway level. METHODS: We
      compared the acute reversibility of forced expiratory volume in 1 second (FEV1)
      after inhalation of albuterol (200 micrograms) in 15 subjects with RADS (12 cases
      caused by chlorine inhalation) with that of 30 subjects with occupational asthma
      (OA) caused by various agents. They were paired according to baseline airway
      obstruction (61% and 63% of predicted value in the RADS and OA groups),
      requirement for medication (bronchodilator only--7 of 15 subjects with RADS and
      14 of 30 subjects with OA--as compared with bronchodilator + inhaled steroids in
      8 of 15 subjects with RADS and 16 of 30 subjects with OA, respectively), and
      interval since removal from exposure (means of 30 and 24 months in the RADS and
      OA groups). In addition, five nonsmokers with RADS who had not received inhaled
      steroids underwent bronchoscopy with lavage and bronchial biopsies less than 2
      years after the exposure. RESULTS: The percentage increase in FEV1 over baseline
      after inhalation of albuterol was 10% +/- 9% in the RADS group and 19% +/- 16% in
      the OA group (p = 0.005). Only 2 of 15 subjects (13%) with RADS and 12 of 30
      subjects (40%) with OA showed an improvement in FEV1 of 20% or greater after
      inhalation of albuterol. Bronchoalveolar lavage showed an increased number of
      cells with a predominance of lymphocytes, and biopsy specimens showed increased
      basement membrane thickness in the five subjects with RADS who underwent
      bronchoscopy. CONCLUSION: Subjects with RADS are generally left with less airway
      reversibility than those with OA. We suggest that this difference is secondary to
      distinct pathologic changes.

PMID- 8308179
TI  - Production of factors with B-cell growth and differentiation activities by
      peripheral blood mononuclear cells from patients with hypogammaglobulinemia.
AB  - BACKGROUND: The maturation of normal B lymphocytes proceeds through a growth
      phase and a differentiation phase. These two phases appear to be under the
      influence of mediators released by immune cells, B-cell growth factor(s), which
      induce proliferation of B cells; and B-cell differentiation factor(s), which
      induce B-cell differentiation. METHODS: We analyzed the ability of peripheral
      blood mononuclear cells from patients with hypogammaglobulinemia to produce B
      cell growth factor and B-cell differentiation factor activity in comparison with
      normal peripheral blood mononuclear cells. RESULTS: Of 27 patients tested, 26 had
      normal production of B-cell growth factor activity. A quantitative but not
      absolute defect in B-cell growth factor production was demonstrable in one boy
      with hypogammaglobulinemia. Interleukin-2 and interleukin-4 levels, as determined
      antigenically in these supernatants, had a similar distribution pattern from
      patients' or from control peripheral blood mononuclear cells; that is,
      undetectable levels of interleukin-2 were produced by cells from 4 of 16 patients
      tested and from 4 of 13 control subjects, and undetectable levels of interleukin
      4 produced by cells from 6 of 16 patients and 4 of 13 control subjects. B-cell
      differentiation factor activity was absent in only one child tested but present
      in all other patients. Two patients had quantitatively low secretion of B-cell
      differentiation factor, but all others were within normal range. The two patients
      with quantitatively depressed B-cell differentiation factor activity had normal
      levels of B-cell growth factor activity, interleukin-2, and interleukin-4
      produced from their cells. CONCLUSION: Peripheral blood mononuclear cells from
      the majority of patients with hypogammaglobulinemia appear to have the capacity
      to produce B-cell growth factors and B-cell differentiation factor activity in
      vitro.

PMID- 8308180
TI  - Influence of mite exposure on symptoms of mite-sensitive patients with asthma.

PMID- 8308181
TI  - Occupational asthma and immunologic responses induced by inhaled carmine among
      employees at a factory making natural dyes.
AB  - Carmine is a natural red dye widely used as a food coloring agent and for
      cosmetic manufacture. It is extracted from the dried females of the insect
      Dactylopius coccus var. Costa (cochineal). Although it has been reported that
      inhalation of carmine may give rise to occupational asthma and extrinsic allergic
      alveolitis, there is little evidence of its immunogenic capacity. We studied nine
      current employees at a factory making natural dyes and one former employee who
      had left this plant after occupational asthma developed. A current employee had
      work-related symptoms of rhinitis and asthma that were confirmed by bronchial
      provocation tests, and another worker had rhinitis. Immunologic sensitization to
      carmine and cochineal was evaluated by means of skin testing and determination of
      serum-specific IgE and IgG subclass antibodies by RAST and ELISA, respectively.
      The specificity of the RAST assay was investigated by RAST inhibition with
      different fractions of carmine. The three workers with respiratory symptoms had
      positive skin prick test reactions to both carmine and cochineal. An immediate
      response to the bronchial provocation test with carmine and cochineal was
      observed in the current employee with asthma. Specific IgE antibodies against
      carmine and cochineal were found only in this worker. RAST inhibition studies
      indicated that the main allergen had a molecular weight between 10 and 30 kd.
      Specific IgG antibodies against carmine and cochineal, mainly the subclasses
      IgG1, IgG3, and IgG4, were found in the 10 subjects surveyed. These findings
      suggest that carmine may induce immunologic responses, most likely IgE mediated
      in workers with symptoms of occupational asthma.

PMID- 8308182
TI  - A clinicopathologic study of ten patients with recurrent unexplained flushing.
AB  - We describe the clinicopathologic features of 10 patients with recurrent
      unexplained flushing. These patients were referred to the National Institutes of
      Health with a diagnosis of mastocytosis or idiopathic anaphylaxis. Both diagnoses
      were eliminated after evaluation. Patients reported attacks of flushing lasting
      15 minutes to 2 days and associated with such symptoms as anxiety, chest
      tightness, paresthesia, slurred speech, weakness, and pruritus. Abdominal pain
      was a constant feature, often associated with cramping and an increase in stool
      frequency. Attacks witnessed by physicians consisted of an exaggerated blush
      response of the face and upper part of the chest, and were sometimes associated
      with tachycardia, mild hypertension, and tachypnea. Hives, angioedema, wheezing,
      and hypotension were not observed. Routine laboratory studies and 5
      hydroxyindoleacetic acid, vanillylmandelic acid, and plasma histamine levels were
      normal. Plasma histamine levels did not elevate during attacks. When performed,
      results of bone marrow examinations, skin biopsies, and bone scans were normal.
      Psychiatric examinations frequently revealed somatization disorders. Patients had
      often been prescribed a wide variety of medications including antihistamines,
      nonsteroidal anti-inflammatory drugs, and steroids, with little or no benefit.
      Despite the benign nature of the clinical and laboratory findings, patients had
      undergone repeated, often invasive, examinations for several years. Whether such
      patients have a prominent flush response exaggerated through a somatization
      disorder or a relatively benign flushing disorder associated with putative
      mediator release remains to be determined. Recognition of this category of
      patients with unexplained flushing will avoid subjecting such patients to
      unwarranted repeated examinations, procedures, and inappropriate therapy.

PMID- 8308183
TI  - Safety and efficacy of oral immunotherapy with standardized cat extract.
AB  - Fifty-three subjects with positive skin prick test results to cat extract and
      rhinoconjunctival symptoms on exposure to cat dander were enrolled in a double
      blind, placebo-controlled study of oral cat immunotherapy. Responses were
      assessed by development of symptoms and nasal blockage on exposure to an
      apartment contaminated with cat dander, by titrated skin prick tests, and by cat
      specific IgG and IgE. A total cumulative dose of 2.5 x 10(6) allergy units or 436
      U Fel d I were administered over a period of 3 months. Both groups of subjects
      had significantly fewer symptoms on exposure to cat dander during the course of
      the study, but there was no significant difference between active and placebo
      groups. There were no significant changes in either group in nasal blockage, skin
      prick test results, or specific IgG levels. Both groups had significant increases
      in cat-specific IgE, but there were no differences between groups. Subjects
      receiving active treatment had a slight excess of gastrointestinal complaints.
      Two subjects receiving active treatment experienced systemic symptoms: one had
      pulmonary edema, and the other had persistent asthma and urticaria, which may
      have represented reactions to the treatment. We conclude that oral cat
      immunotherapy with the preparation and doses used in this study is not effective.

PMID- 8308184
TI  - Evaluation of the overall degree of sensitization to airborne allergens by a
      single serologic test: implications for epidemiologic studies of allergy.
AB  - In most epidemiologic studies of respiratory allergy, the overall degree of
      sensitization is usually measured by indices based on skin prick test reactions
      to a panel of relevant airborne allergens. In the present study we used a single
      assay (CAP-Phadiatop, Pharmacia, Uppsala, Sweden), which is based on the reaction
      between serum-specific IgE and a mixture of locally relevant inhalant allergens
      to measure the degree of sensitization to inhalants in the sera of 1815 young
      Italian men, in whom a complete diagnostic workup for respiratory allergy was
      performed in parallel. The intensity of reaction in the CAP-Phadiatop assay was
      highly correlated with: (1) an allergy index (p < 0.005), based on skin prick
      test reactivity to seven relevant inhalant allergens (Dermatophagoides
      pteronyssinus, mixed grass pollens, cat epithelium, Parietaria judaica, Olea
      europaea, Artemisia vulgaris, Alternaria tenuis); (2) the concentration of
      specific IgE to the same allergens, measured by CAP-RAST (p < 0.001), in both
      monosensitized and polysensitized subjects; (3) the rate of respiratory allergic
      diseases (p < 0.0001). Therefore CAP-Phadiatop intensity of reaction is a
      reliable indicator of the overall degree of sensitization to inhalant allergens.
      Furthermore, as demonstrated by relative operating characteristic analysis, it
      has an acceptable detectability power in identifying subjects with symptomatic
      expression of the atopy status [P(A) = 0.948]. The evaluation of the degree of
      sensitization to inhalants by a single and semiautomated assay represents a step
      forward in the standardization of procedures for epidemiologic studies of
      inhalant allergic diseases and for mass screening programs, which are aimed at
      identifying predictive markers of disease susceptibility.

PMID- 8308185
TI  - Comparison of rhinomanometry, symptom score, and inflammatory cell counts in
      assessing the nasal late-phase reaction to allergen challenge.
AB  - Inspiratory nasal resistance, symptom score, and influx of inflammatory cells
      into the nose were evaluated before and after a nasal challenge in 15 patients
      with grass pollen rhinitis and in six nonallergic control subjects, to study the
      nasal late-phase reaction and its relationship with nasal cytology. All patients
      had an immediate positive reaction to specific nasal challenge. In seven allergic
      subjects we observed a later inspiratory nasal resistance increase, but only two
      had a significant late symptom score. Inflammatory cells increased by 8 hours in
      all the patients; the higher the cell influx, the higher the symptom score. Close
      correlations were found between the inspiratory nasal resistance increase, nasal
      obstruction at hours 8 and 24, and all cell counts. In control challenges there
      were no significant increases of symptom score or inspiratory nasal resistance
      either during the challenge or in the next 24 hours. A weakly significant
      increase was found only for neutrophil counts at 8 hours. These results indicate
      that an inflammatory reaction constantly occurs after a specific nasal challenge;
      its extent is closely related to inspiratory nasal resistance and to the
      intensity of nasal obstruction. Moreover, our data outline the pivotal role
      played by eosinophils and basophils in the genesis of an allergic late-phase
      reaction in the nose.

PMID- 8308187
TI  - 6 x 1 = 1: Part III.

PMID- 8308186
TI  - The production of interferon-gamma in response to a major peanut allergy, Ara h
      II correlates with serum levels of IgE anti-Ara h II.
AB  - The current study was undertaken to examine the potential role of T cells in the
      pathogenesis of peanut allergy. Peripheral blood mononuclear cells (PBMCs) from
      patients with peanut allergy, patients with asthma, and nonatopic normal control
      subjects were assessed for proliferation after stimulation with a 17 kd major
      peanut allergen (Ara h II), ovalbumin, casein, soy, and Candida albicans. We
      found that Ara h II and C. albicans induced significantly higher levels of
      proliferation than ovalbumin, casein, and soy. Because interferon-gamma (IFN
      gamma) and interleukin-4 (IL-4) play critical roles in IgE regulation, we
      assessed the production of these cytokines after stimulation with C. albicans and
      Ara h II. C. albicans stimulated similar levels of IFN-gamma in all three study
      groups. In contrast, after stimulation with Ara h II, culture supernatants from
      PBMCs of subjects with peanut allergy contained significantly lower levels of IFN
      gamma than did the PBMCs of the two control groups (p = 0.02). More important,
      there was a significant (p = 0.05) inverse correlation between the serum IgE anti
      Ara h II levels and IFN-gamma production by PBMCs from the respective peanut
      allergic patients. IL-4 protein was not detected in culture supernatants of PBMCs
      stimulated with Ara h II. However, amplification of cytokine gene transcripts by
      polymerase chain reaction did demonstrate IL-4 expression in Ara h II-stimulated
      PBMCs from both patients with peanut allergy and control subjects. These data
      suggest that the level of IFN-gamma production in response to Ara h II may be an
      important factor in determining the development of peanut-specific IgE responses.

PMID- 8308188
TI  - Is there a prevention and treatment strategy for macular degeneration?
AB  - BACKGROUND: Reduced antioxidant defense of the retina secondary to poor nutrition
      and smoking combined with increased life expectancy and exposure to solar
      radiation can provide a triple assault on the aging retina. If left untreated,
      without prophylactic measures, 7.5 million American adults will suffer vision
      loss from ARM by the year 2020. METHODS: Better known pathobiologic
      interrelationships between ARM, nutritional/antioxidant status and UV/blue
      visible solar exposure risk based on animal research and recent epidemiologic
      studies is presented, along with an overview of ocular free radical biochemistry.
      RESULTS: Because ARM begins parafoveally, and confounding ocular lens changes
      often occur, there have been practical clinical/research difficulties in early
      diagnosis, and assessing improvement/loss from nutritional intervention.
      Threshold Amsler grid testing, contrast sensitivity and more recently red foveal
      flicker fusion frequency testing are presented as promising tests for discerning
      subtle pathologic and functional changes in vision. CONCLUSIONS: A conservative
      prevention/treatment strategy is presented involving identification of at-risk
      patients, solar radiation protection, nutritional counseling based on the new
      USDA Food Pyramid concept and vitamin/mineral supplementation if necessary for
      non-compliant high risk patients. Excessive vitamin intake of particular
      micronutrients has some drawbacks, and the optometrist should be aware of the
      implications of self-prescribed OTC ocular formulations, the difference between
      UV risk vs. "blue light hazard" and ongoing clinical trials.

PMID- 8308189
TI  - Infection control: guidelines for the optometric practice. AOA Primary Care and
      Ocular Disease Committee.

PMID- 8308190
TI  - Evaluation of dietary antioxidant levels and supplementation with ICAPS-Plus and
      Ocuvite.
AB  - BACKGROUND: Oxidative damage caused by free radicals has been implicated in the
      development of age-related macular degeneration (ARMD). Recent studies suggest
      that antioxidant vitamins and minerals can be useful for the management and/or
      prevention of this condition. METHODS: To assess the normal dietary intake of the
      antioxidants, 28 healthy subjects 55 years of age and over completed a diet
      survey. Then two over-the-counter (OTC) nutritional supplements that make claims
      about the antioxidant nutrients they contain (ICAPS-Plus and Ocuvite) were
      evaluated with respect to their ability to raise blood levels of two important
      antioxidant nutrients: zinc and beta-carotene. RESULTS: Based on the diet survey,
      26 of the 28 subjects were found to have deficient intakes; zinc and selenium
      were the most commonly deficient nutrients. Following a 2-week administration
      period, both ICAPS-Plus and Ocuvite significantly raised mean serum zinc levels
      24.7 percent and 18 percent respectively; ICAPS-Plus significantly raised mean
      beta-carotene levels by 21.4 percent, but Ocuvite did not change the mean level
      significantly. CONCLUSIONS: Based on the probable relationship between
      antioxidant levels and diseases such as ARMD, these results suggest that OTC
      supplements might be useful for selected patients.

PMID- 8308191
TI  - Free radicals and antioxidant supplementation: a review of their roles in age
      related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration (ARMD) is a major cause of blindness
      in the elderly. Unfortunately, no proven form of treatment is currently available
      for the dry, atrophic form of ARMD seen in more than 90 percent of patients with
      this condition. METHODS: A recent theory suggests that ARMD is associated with
      damage to the retina caused by free radicals. If this is correct, it is possible
      that the damage could be prevented or moderated by supplementing the diet with
      specific antioxidant vitamins and minerals that enhance the body's natural
      defenses against free radicals. RESULTS AND CONCLUSION: This paper reviews the
      literature regarding the pathogenesis of ARMD and presents a rationale for its
      management or prevention by the use of supplemental vitamins and minerals.

PMID- 8308192
TI  - A novel way to generate nonspecifically radiolabeled proteins for use as
      molecular-weight markers.
AB  - A method for labeling proteins using radioactive nucleotides in the presence of
      divalent cations such as Cu2+, Zn2+ and Cd2+ is described. Small amounts of
      marker proteins can be rapidly labeled using the method and they can be used for
      molecular-weight determination of radioactive proteins of unknown molecular
      weights, as for example, any protein labeled with 35S-methionine in vivo or any
      protein radiolabeled by 32P in protein phosphorylation experiments. The gels in
      which the labeled markers and the proteins of unknown molecular weight are
      electrophoresed could be directly exposed to X-ray films and comparisons made
      from a single autoradiogram, avoiding a two step procedure of Coomassie blue
      staining followed by autoradiography and aligning of the two sets of bands. This
      metal-ion-mediated labeling of proteins described in the present communication is
      not by any site-specific interaction of the nucleotide with the proteins and the
      protein is denatured after the complex formation. The adducts, once formed, are
      stable under conditions of SDS-PAGE or EDTA treatment. It is suggested that
      proteins labeled under conditions described in this communication are ternary
      complexes involving aromatic residues of the proteins, nucleotides and the
      divalent cations.

PMID- 8308193
TI  - Generation and detection of hydroxyl radical in vivo in rat spinal cord by
      microdialysis administration of Fenton's reagents and microdialysis sampling.
AB  - We developed a double microdialysis fiber technique to generate hydroxyl radicals
      (OH.) in rat spinal cord. H2O2 and FeCl2/EDTA were pumped through two parallel
      microdialysis fibers inserted into the spinal cord such that the reactants mix in
      the tissue to generate OH. by the Fenton reaction. Generated OH. was detected by
      administering phenylalanine through one fiber and measuring o-, m- and p
      hydroxyphenylalanine in collected dialysates by high pressure liquid
      chromatography and fluorescence detection. The hydroxyphenylalanines are produced
      by OH. attacking the phenylalanine. OH. generation was also accomplished in in
      vitro experiments and the results were consistent with in vivo experiments. This
      novel method to generate and measure OH. radical in vivo overcomes difficulties
      in studying damage to tissue by short-lived OH.. Although developed to study the
      role of OH. in spinal cord injury, this method could be used to study other
      diseases involving OH. damage.

PMID- 8308194
TI  - Cytosolic 5'-nucleotidase/nucleoside phosphotransferase: a single assay for a
      bifunctional enzyme.
AB  - Cytosolic 5'-nucleotidase/nucleoside phosphotransferase has been purified from
      calf thymus. Since the same protein is able to catalyze both the hydrolysis and
      the interconversion of several nucleoside monophosphates, it is necessary to
      study the effect of different metabolites and assay conditions on both activities
      in order to elucidate their physiological roles. We describe herein a method
      which allowed us to follow both activities contemporaneously in the same assay
      mixture. The method takes advantage of the observation that deoxyGMP is both a
      good substrate for hydrolysis and a good phosphate donor for the
      phosphotransferase reaction, but its dephosphorylated product, deoxyguanosine, is
      not a phosphate acceptor. As a consequence, it is possible to follow both the
      deoxyguanosine production and the transfer of phosphate from deoxyGMP to the best
      phosphate acceptor, inosine, during the reaction, applying a method for the
      chromatographic separation on HPLC of both substrates (inosine and deoxyGMP) and
      both products (IMP and deoxyguanosine). The method was applied to the
      determination of the KM for inosine.

PMID- 8308195
TI  - Dependence of whole blood luminol chemiluminescence on PMNL and RBC count.
AB  - Luminol chemiluminescence (LCL) of whole blood as response to zymosan stimulation
      was used to assess the activity of polymorpho-nuclear leukocytes (PMNLs). Since
      PMNL and red blood cells (RBCs) are the primary components determining LCL
      response, the influence of PMNL and RBC count on the response was investigated
      over wide ranges of cell count and time interval. A linear relationship was found
      between maximum LCL intensity (Imax) (reflecting PMNL activity) and PMNL count.
      This allows a proper correction of Imax to be made as related to the sample PMNL
      count. This correction was valid for PMNL concentrations from 3.10(3) PMNL/ml to
      6.10(5) PMNL/ml. When concentrations range from 6.10(3) PMNL/ml to 3.10(4)
      PMNL/ml the relationship was valid for a time interval round the peak. During the
      same interval the inhibitory effect of RBC count was studied. A correction of LCL
      was found possible for different RBC concentration ranging from 2.5.10(6) RBC/ml
      to 10(8) RBC/ml. These independent corrections of LCL response to PMNL and RBC
      counts were applied to diluted whole blood samples. The common correction of Imax
      was applicable in dilutions not less than 1:50. To correct light intensity for
      the time interval around Imax, the dilutions used had to be not less than 1:200.
      The results obtained permit an objective assessment of PMNL activity to be made
      by testing whole blood samples from different individuals and/or samples diluted
      to different extents.

PMID- 8308196
TI  - Batch isolation of hen egg white lysozyme with magnetic chitin.
AB  - Biospecific magnetic sorbent for lysozyme isolation (magnetic chitin) has been
      prepared from magnetic chitosan after acetylation with acetic anhydride. The
      capacity of magnetic chitin was 2.5 mg of lysozyme per 1 ml of sorbent.

PMID- 8308197
TI  - [Immunological recognition in pregnancy: physiology].
AB  - In the last decade works on the responses of the mother's immune system to the
      presence of the feto-placental unit have burgeoned. The antigens that are
      presented to the mother are special because the trophoblast does not show
      classical transplantation antigens which are classically implicated in graft
      rejection. A class I antigen, antigen HLA-G is present in the extra-villous
      cytotrophoblast, different from classical antigens by virtue of its molecular
      weight and its reduced antigenic polymorphism. Many functions have been
      attributed to this antigen; most of them are still being evaluated. The most
      important immunological phenomena are found at the feto-placental interface.
      Several events occur simultaneously or successively. Recognition of the
      trophoblast brings about an inflammatory reaction which is the initial phase of
      graft rejection. The numerous cytokines that are produced in this initial phase
      allow decidualization to occur and for the embryo to implant when it has reached
      an adequate stage of evolution. Rapidly, immunosuppressant mechanisms stop this
      rejection reaction which if not stopped can cause the pregnancy to end. There is
      a delicate equilibrium between the different cytokines, those favourable to
      pregnancy and those damaging to pregnancy. The trophoblast which is resistant to
      factors which would cause rejection protects the fetus particularly if its growth
      is helped along by certain cytokines. On the other hand, other cytokines are
      prejudicial to the growth of the trophoblast and activate certain cytotoxic cells
      which become aggressive. The maternal immune system and the endocrine system work
      together to maintain this cytokine network which if destabilized leads to certain
      pathological situations. Disturbances can be due to poor maternal recognition
      particularly if the trophoblast does not give out good antigens, or if the mother
      is genetically programmed not to respond although the disturbance can come from
      external factors such as certain infections.

PMID- 8308198
TI  - [Current indications for colposcopic examination].
AB  - OBJECTIVE: It has become necessary to set out exactly the indications for
      colposcopic examination and to improve out-patient therapy. A response has been
      made to the ever increasing pre-cancerous pathological conditions of the lower
      genital tract. TYPE OF STUDY: A review of the pathological conditions of the
      lower genital tract has led to colposcopic examinations being carried out to work
      out how far grounded its indications are. The authors particularly lead to the
      future for colposcopy and histology of so called "atypical" cytology. MATERIAL: A
      review of the literature and a retrospective study of the agreement between the
      cytology and the histology in 1,454 patients who were examined and followed up at
      the centre for laparoscopy and colposcopy between 1.1.1987 and 31.12.1991. THE
      PRINCIPLE: A study of the information is being gathered about the cytological,
      colposcopic and histological diagnoses. PRINCIPLES RESULTS: Dysplasias diagnosed
      cytologically were confirmed in 95% of cases by colposcopic examination and by
      the results of directed biopsy. In over 90% cases of smears showing "atypical"
      cells the colposcopy confirmed the pathology that was found and in more than 85%
      of cases the histological examination confirmed a papillomavirus lesion or a
      dysplasia of the cervix or elsewhere in the lower genital tract. CONCLUSION: Over
      and above the indication for colposcopic examination, cytological dysplasias were
      found and to were condylomata of the lower genital tract or leukoplakia of the
      vulva, and one has to add "atypical" smears. Furthermore repeating a smear in
      cases of atypical cytology is useless, and can be deceptive. Systemic control of
      the vulva and vagina has to be carried out when the cervix is examined because
      there is a frequent association of dysplasic lesions and there is a possible
      presence of isolated extracervical lesions when cytologically pathological smears
      are found.

PMID- 8308199
TI  - [Cervical cancer before 35 years of age: epidemiological and prognostic aspects.
      Retrospective study of 46 cases of cervical cancer before 35 years of age in a
      series of 449 cases in stages IA2 and IV].
AB  - OBJECTIVE: To investigate the diagnosis and prognosis aspects of carcinoma of the
      cervix in a group of young patients less 35 years old, not very clear in
      literature. STUDY: Retrospective and comparative diagnostic and prognostic study.
      This study is related to the epidemiology and prognosis of such cervical cancer
      in young women. SUBJECTS: Of 449 new patients with carcinoma of cervix FIGO
      stages IA2-IV treated between 1972-1990 inclusive, 46 patients were aged less
      than 35 years old. RESULTS: The frequency is about 10.2%; during the last 20-year
      period, there was a gradual rise in the proportion of young women with invasive
      carcinoma of the cervix (7.6% between January 1972 and June 1981, 13.9% between
      July 1981 and December 1990). There is more frequent incidence of adenocarcinoma
      in the young women group (19.6% adenocarcinoma < 35 years, 8.2% > 35 years). The
      overall 5-year survival all stages together is better before 35 years (71% < 35
      years, 50% > 35 years), because in women aged less than 35 years, early stages
      disease (IA2, IB), predominated. Stage for stage, the 5-year survival is a little
      lower for stage I (78.6% < 35 years, 88.5% > 35 years) and much lower for stage
      II (45.5% < 35 years, 71% > 35 years). The young age is an independent prognosis
      factor, predicting early recurrences within 20 months: the relative risk is 3.7.
      CONCLUSION: The young age (less than 35 years), is a worse prognosis factor of
      carcinoma of the cervix; the treatment is very difficult: heavy (radiotherapy,
      neoadjuvant chemotherapy), efficient, problem of femininity.

PMID- 8308200
TI  - [Cervical cancer in the young woman].
AB  - OBJECTIVE: To study the frequency, the histological type, the stages, and
      prognosis of cancer of the cervix in women under 35 years of age or less. METHOD:
      A retrospective analysis of a series of 1,024 cases notes of which 63 dealt with
      young women. The therapeutic modalities are the same throughout the whole
      duration of the study from 1975-1988. RESULTS: There was no increase in the
      incidence of cancer in young women. The incidence of epidermoid cancer dropped.
      However, mixed adenosquamous tumours were more frequent. There is a predominance
      of stages I cancers. The survival taking all stages together is at 5, 10 and 15
      years better in young women. All the same, taking stage by stage there is no
      difference in the prognosis.

PMID- 8308201
TI  - [Familial cancer of the ovary. A family with 6 index cases].
AB  - Greggi and Kerlikowske have worked out that a woman has a 1.4% chance of
      developing ovarian cancer during her life. When cancer of the ovary is found, 5
      to 10% of these cases have a familial form of this pathology. Thus there are some
      hereditary forms of cancer of the ovary and Lynch has demonstrated that there are
      three types of hereditary associations with ovarian neoplastic pathology:
      specific familial cancer of the ovary, cancer of the ovary associated with
      endometrial cancer and with non-polypoidal cancer of the caecum and rectum,
      cancer of the ovary associated with cancer of the breast. The clinical material
      we are presenting here is of the first type of association and we are reporting
      the study of a family in which 6 members in two generations had cancer of the
      ovary and of whom one had cancer of the breast as well. Familial cancer of the
      ovary shows different characteristics coming on as it does earlier (ten years
      earlier) and with a shorter length of survival (1.8 as against 5 years). The risk
      of the next generation having ovarian neoplastic pathology is clear because there
      is a 50% chance in a patient who has a history of cancer of the ovary in at least
      two first degree relatives. For most daughters when this type of familial cancer
      is found it is justifiable to carry out prophylactic oophorectomy from the age of
      35 year onwards. Particular supervision should be carried out for patients who
      are members of a family where 2 index cases have been found within 20-35
      years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308202
TI  - [Endocystic echography by laparoscopy. 6 preliminary cases].
AB  - The decision whether to ablate an ovarian cyst using the operating laparoscope
      depends on a whole bundle of clinical, biological, ultrasound and laparoscopic
      factors. But opening a uni or multi-locular fluid containing cyst and exploring
      its walls can leave the operator in doubt as to whether it is benign, malignant
      or a borderline lesion. Now it is possible to use 3 mm catheters carrying a
      rotary ultrasound transducer. When this sound is placed inside a cyst it is
      possible to study the walls topographically. Six preliminary cases are presented;
      the increased sensitivity of the pictures obtained by this miniaturised sound
      make it possible to improve ultrasound diagnosis.

PMID- 8308203
TI  - [Pulmonary lymphangioleiomyomatosis and sex hormones].
AB  - The authors having prepared for a case of pulmonary lymphangioleiomatosis point
      out the diagnostic boundaries of this condition with benign metastasizing
      intravenous leiomyomas of the uterus, pulmonary localisation of Bourneville's
      tuberous sclerosis and the important aetio pathologic role of sex hormones.
      Finally they deal with the therapeutic management and the various uses of
      hormones to inhibit oestrogenic activity.

PMID- 8308204
TI  - [Giant breast fibroadenoma].
AB  - We report a case of giant fibroadenoma of the breast, "juvenile type", in a 15
      year old girl. We study the characteristics of this tumor that occurs in
      adolescents females, the differential diagnosis with cystosarcoma phylloide and
      benign virginal hypertrophy, and treatment. Follow-up is recommended because of
      possible recurrent tumor of a short time.

PMID- 8308205
TI  - [Ivemark syndrome: 2 case reports].
AB  - Ivemark Syndrome is a multiple organ syndrome associated with splenic
      abnormalities, complex cardiac pathology and an abnormality of the abdominal
      viscera. The incidence in our department is 1/6000 deliveries and the teratogenic
      effect seems to occur between the 30th and 40th days of intrauterine life, but
      the cause is unknown. The principal warning signal is bradycardia. Prenatal
      diagnosis can be made by ultrasound. The prognosis depends on the degree of
      malformation of the heart.

PMID- 8308206
TI  - [Congenital auriculo-ventricular block and anti-Ro (SS-A)/anti-La (SS-B)
      antibody].
AB  - Congenital heart blocks due to immunological causes are rare. A case is reported
      of a fetus with auriculo-ventricular block diagnosed at 22 weeks of amenorrhoea
      and intrauterine death at 32 weeks. The authors discussing the case find the most
      likely link: an anti-RO (SS-A) and anti-LA (SS-B) immunological block and they
      suggest that there are minor localised lesions in the nodal tissue which gives
      rise to benign disturbances of cardiac rhythm and they point out ways of
      preventing intrauterine auriculo-ventricular block.

PMID- 8308207
TI  - [Pregnancy in a rudimentary uterine horn].
AB  - The authors report a case of pregnancy in a rudimentary horn diagnosed by
      laparotomy. The location could not be suspected by any clinical sign. This
      pregnancy stopped at 19 weeks of amenorrhoea. Any attempts of induction of labour
      failed. Laparotomy was necessary to assess the diagnosis and to allow the
      resection of the uterine horn. The authors present a review of literature.

PMID- 8308208
TI  - [Maternal fetal choriocarcinoma after normal delivery].
AB  - Materno-fetal choriocarcinoma discovered after a normal delivery is very rare.
      The risks for choriocarcinoma after a pregnancy at term is estimated at 1 in
      100,000. All the same the ease with which the diagnosis is made by levels of
      plasma beta-hCG makes it possible to think of this possibility after delivery
      when there is maternal pathology which cannot be diagnosed or a fetal tumour that
      cannot be labelled. The transmission of this illness from mother to fetus evokes
      discussion about the tolerance of an allograft.

PMID- 8308209
TI  - [Gifts authorized under some conditions. The law on gifts to physicians].

PMID- 8308210
TI  - Nasal continuous positive airway pressure. A new treatment for nocturnal
      gastroesophageal reflux?
AB  - Nasal continuous positive airway pressure (CPAP) reduces nocturnal
      gastroesophageal reflux (GER) in obstructive sleep apnea syndrome (OSAS)
      patients. The primary objectives of our investigation were to determine if CPAP
      could reduce reflux in non-OSAS patients and, if so, by what mechanism.
      Esophageal pH was monitored for 48 h in six nocturnal reflux patients. During the
      first 24 h, basal reflux data were collected; the second night, nasal CPAP was
      administered (pressure = 8 cm H2O). Esophageal manometry was obtained in six
      healthy adult volunteers both on and off nasal CPAP (pressure = 8 cm H2O) to
      ascertain CPAP's effects on esophageal pressure and peristalsis. The six reflux
      patients experienced less nocturnal GER while on CPAP. The mean percent time
      esophageal pH < 4 was reduced from 27.7 +/- 10.0 to 5.8 +/- 2.6 (p < 0.004); the
      mean reflux duration dropped from 2.1 +/- 0.6 to 0.9 +/- 0.5 min (p < 0.03); and
      the mean duration of longest reflux improved from 84.3 +/- 32.6 to 13.8 +/- 6.9
      min (p < 0.01). The CPAP raised the mean resting midesophageal pressure by 4.4 cm
      H2O (p < 0.01) and the mean resting lower esophageal pressure (LES) by 13.2 cm
      H2O (p < 0.02) in the healthy volunteers. Nasal CPAP effectively reduced
      nocturnal GER in six patients with nocturnal reflux. The antireflux activity of
      CPAP is likely due to passive elevation of intraesophageal pressure and possibly
      to reflex LES constriction.

PMID- 8308211
TI  - Esophageal dysfunction does not always worsen in systemic sclerosis.
AB  - Using the manometric method, we studied the progression of esophageal involvement
      in 17 women with a diagnosis of systemic sclerosis (SSc) and compared the results
      with those obtained for 14 healthy women. The manometric examination of SSc
      patients was performed twice, with an interval of 9 to 111 months (median, 40
      months). All patients had peristaltic contractions in the proximal esophagus.
      Eight had peristaltic contractions, and 9 had no contraction in the middle and
      distal esophagus. The lower esophageal sphincter pressure and the amplitude of
      contractions in the esophageal body were lower in SSc patients than in controls.
      The duration of contractions was the same in SSc patients and controls. The
      velocity of peristaltic contractions did not differ between patients and controls
      in the distal esophagus, but was higher in SSc patients in the proximal
      esophagus. In 16 patients, no difference in lower esophageal sphincter (LES)
      pressure, esophageal contraction amplitude, duration, and velocity was observed
      between the first and second evaluation. In one patient, the distal esophageal
      contractions changed from peristaltic to completely absent, and the lower
      esophageal sphincter pressure changed from 20.2 mm Hg to 5.1 mm Hg. The results
      suggest that the esophageal involvement of SSc patients was not progressive in
      all cases.

PMID- 8308212
TI  - Acute pancreatitis in Crohn's disease.
AB  - Pancreatitis as an extraintestinal manifestation of Crohn's disease (CD) is
      controversial. We review the episodes of acute pancreatitis in patients with CD.
      Of 852 patients, 12 developed clinically overt pancreatitis, representing a
      frequency of 1.4% in a follow-up period of 10 years. In 10 patients, common
      causes of pancreatitis were excluded. In 2 patients, drug-induced disease
      (azathioprine, sulfasalazine) could not be ruled out. Recurrence of pancreatitis
      was observed in only 2 patients. Younger patients and those with active disease
      seemed more at risk for development of pancreatitis. If prednisolone was needed
      for treatment of active CD, no adverse effect was observed for the pancreatitis.
      Along with the clinical features, we studied autoantibodies against exocrine
      pancreas; the incidence of autoantibodies in patients with pancreatitis was the
      same as in the controls who did not develop pancreatic abnormalities. This does
      not support the hypothesis that acute pancreatitis in CD is associated with the
      formation of pancreatic autoantibodies.

PMID- 8308213
TI  - Peptic ulcer on a Kibbutz in Israel: 1930-1990.
AB  - In the last 30 years, many changes have occurred in the epidemiology and natural
      history of peptic ulcer disease. During the 60 years since Kibbutz Afikim's
      beginning, 94 members have been diagnosed with duodenal or gastric ulcer. Seventy
      one percent were males, 29% died. Ninety-four percent of the patients were
      diagnosed by barium meal only. Six patients had a gastric ulcer. The incidence
      rate among adults was 0.6% through the mid-1940s; the rate decreased to 0.3% by
      the end of the 1970s and to 0.1% in the 1980s. The decrease was noted for both
      sexes. The prevalence rate among adults since the 1970s has been 7%. In one
      fourth of the patients, an ulcer was diagnosed before age 30 and in another
      fourth after age 50. An average of 3.1 upper gastrointestinal radiographs were
      done per patient. There was no temporal relationship between the incidence and
      the stressful effects of arrival in Israel or at the Kibbutz. Twenty-four
      patients underwent surgery: In the last decade there seemed to be a slight
      decrease in elective surgery.

PMID- 8308214
TI  - Treatment of chronic hepatitis B in children with recombinant alfa interferon.
      Different response according to age at infection.
AB  - The objective of this study was to investigate the possibility of predictive
      factors of response to treatment with interferon in children with chronic
      hepatitis B virus infection. We analyzed the influence on the response rate of
      age, sex, mode of acquisition of infection, severity, and duration of disease in
      16 children with chronic hepatitis B treated with 3 MU of recombinant alpha
      interferon 2b three times a week for 6 months. Six months after the end of
      treatment, eight patients (50%) had cleared HBV DNA, seroconverted to anti-HBe
      and normalized serum transaminase values. Response was significantly higher in
      those whose serum transaminase levels were > 100 IU/liter before treatment (70%)
      and those infected after birth (72%) compared with those with lower serum
      transaminase levels (16%) and those infected at birth (7%). Our findings indicate
      that a 6 month course of low dose interferon (3 MU) is highly effective in
      children with horizontally transmitted chronic hepatitis B virus infection, but
      noneffective in children infected at birth.

PMID- 8308215
TI  - Metastatic Crohn's disease. A rare cutaneous manifestation.
AB  - Cutaneous extraintestinal manifestations of Crohn's disease are common. Lesions
      contiguous with the gastrointestinal tract, such as perianal, peristomal, and
      perifistular inflammation are characterized by the histologic demonstration of
      granulomas. Rarely a cutaneous granulomatous lesion occurs that is noncontiguous
      with the gastrointestinal tract and is separated from it by normal skin. We
      report axillary "metastatic" Crohn's disease that appeared with exacerbation of
      the inflammatory bowel disease and responded well to steroid therapy.

PMID- 8308216
TI  - Neuroendocrine carcinoma of the colon. Correct diagnosis is important.
AB  - Neuroendocrine carcinomas of the colon and rectum are unusual and have in the
      past been misrepresented as either carcinoid tumors or undifferentiated cancers.
      Colorectal neuroendocrine tumors comprise a clinicopathologic spectrum that
      ranges from indolent to highly aggressive. The case discussed illustrates the
      importance of the right diagnosis because it will affect treatment and may better
      predict the clinical course.

PMID- 8308217
TI  - Hepatic teratoma in an adult. Case report with a review of the literature.
AB  - Teratomas of the liver in adults are rare. We believe this to be only the fifth
      such case reported, the first with CT correlation and with plain film
      documentation of the development and slow progression of the lesion from age 44
      to 61. A review of the literature regarding hepatic teratomas is appended.

PMID- 8308218
TI  - Fulminant hepatic failure after methotrexate and PUVA therapy for psoriasis.
AB  - Acute hepatic failure developed after 8-methoxypsoralen and ultraviolet
      irradiation for psoriasis in a patient with prior methotrexate-induced cirrhosis.
      Review of the literature and the temporal relationship between 8-methoxypsoralen
      and hepatic injury in our patient suggests it may be a direct hepatotoxin. In our
      report, submassive necrosis superimposed on cirrhosis appears to have produced
      hepatic failure.

PMID- 8308219
TI  - An incarcerated peristomal gastric hernia causing gastric outlet obstruction.
AB  - A 77-year-old woman had had several 3-day episodes of nausea and vomiting for 3
      years. Upper endoscopy led to findings consistent with pyloric outlet
      obstruction, and barium studies demonstrated an incarcerated peristomal gastric
      hernia. This is taken to be the third description of this diagnosis. We discuss
      the pathophysiology of gastric hernias.

PMID- 8308220
TI  - A case of cyclosporine-sensitive, steroid-resistant, autoimmune chronic active
      hepatitis.
AB  - Few alternative treatments are available for those patients with autoimmune
      chronic active hepatitis who fail to respond to the conventional treatment of
      corticosteroids. Such patients have a poor prognosis and frequently require liver
      transplantation. We report a patient with autoimmune hepatitis who failed
      treatment with corticosteroids and azathioprine. He responded to treatment with
      cyclosporine but relapsed with its discontinuation; reinstitution of the
      cyclosporine again induced remission. Cyclosporine appears to be an effective
      alternative treatment in patients with steroid-resistant, autoimmune chronic
      active hepatitis; its use may preclude or delay liver transplantation.

PMID- 8308221
TI  - 99mTc colloid and 99mTc IDA imagings in diffuse hepatic disease.
AB  - Ninety-six patients with various diffuse hepatic diseases were observed using
      both 99mTc colloid and 99mTc iminodiacetic acid (IDA), focusing on the potential
      etiologies of the disease process as well as its chronicity and severity. The
      presence of acute hepatic disease was more sensitively depicted with 99mTc IDA
      than with 99mTc colloid. In chronic hepatic disease, on the other hand, 99mTc
      colloid and 99mTc IDA demonstrated a similar sensitivity. The potential etiology
      of the disease process (differential diagnosis) and the chronicity of the disease
      could be evaluated better with 99mTc colloid. Among the patients with different
      stages of liver cirrhosis, however, 99mTc IDA significantly discriminated the
      severity of the hepatic disease. These results suggest that 99mTc IDA may be used
      to determine the degree of functional disorder in acute hepatic disease and
      evaluate the severity of diffuse hepatic disease, whereas 99mTc colloid can
      effectively evaluate the potential etiology and chronicity of the disease.

PMID- 8308223
TI  - Jejunal polyps in familial adenomatous polyposis assessed by push-type endoscopy.
AB  - Cancer of the upper gastrointestinal tract is a leading cause of death in
      patients with familial adenomatous polyposis who have previously undergone total
      colectomy. The prevalence and the degenerative risk of gastric and duodenal
      adenomas has been well documented, but little is known about the occurrence of
      jejunal polyps in these patients. We evaluated 21 (16 affected and five high
      risk) subjects in nine families prospectively in order to assess the frequency of
      polyps in the upper jejunum. With the push-type technique, it has been possible
      to insert a standard gastroduodenoscope or a longer fiberscope 15-80 cm beyond
      the ligament of Treitz. Eight out of 16 (50%) affected patients and none of the
      nonaffected subjects had polyps. All lesions were adenomas, including a 4-cm
      tubulovillous adenoma with severe dysplasia, and were almost exclusively located
      in the first 20 cm of jejunum. The depth of insertion obtained with
      gastroduodenoscopes was significantly smaller than that obtained with longer
      endoscopes (pediatric colonoscope or experimental enteroscope). However, the
      jejunal area thought to be at the highest risk of adenoma (the proximal 20 cm)
      was usually investigated even with standard 105-cm long gastroduodenoscopes. This
      study confirms that the upper jejunum has a high prevalence of adenomas in
      patients affected by familial adenomatous polyposis and that proximal jejunoscopy
      is a worthwhile, not excessively uncomfortable procedure that should be added to
      the usual follow-up protocols.

PMID- 8308222
TI  - Enterocolic lymphocytic phlebitis. Clinical, radiologic, and pathologic features.
AB  - Venous compromise as a cause of ischemic colitis and enteritis is infrequent.
      Enterocolic lymphocytic phlebitis, a rare cause of such compromise, to our
      knowledge has been reported in only three patients. We describe a patient with
      this condition who had hematochezia and a cecal mass that was mistaken
      endoscopically and radiologically for carcinoma and required resection. The mass,
      which was ulcerated, was due to intense submucosal edema. The patient had no
      history of taking hydroxyethylrutoside, a drug used in Europe in treating
      varicose veins that has been implicated in all three previously reported cases.
      This entity is characterized by a mixed T- and B-cell vasculitis affecting veins
      exclusively in the wall and mesentery of the colon and small bowel, without
      systemic involvement, leading to fibrointimal proliferation, thrombosis, venous
      occlusion, and subsequent edema and ischemic necrosis. It should be distinguished
      from other enterocolic phlebitides, including Behcet disease, systemic lupus
      erythematosus, and myointimal hyperplasia of mesenteric veins, and can be treated
      by local excision of the affected bowel.

PMID- 8308224
TI  - Upper digestive hemorrhage secondary to the rupture of the splenic artery as the
      first sign of a squamous gastric carcinoma.

PMID- 8308225
TI  - Subcutaneous seeding of hepatocellular carcinoma following fine-needle aspiration
      biopsy.

PMID- 8308226
TI  - Primary Kaposi's sarcoma of the gallbladder in AIDS.

PMID- 8308227
TI  - Neurobiology of inflammatory bowel disease.

PMID- 8308228
TI  - Celiac sprue and insulin-dependent diabetes mellitus.

PMID- 8308229
TI  - Experience with the hemophiliac child in a pediatric emergency department.
AB  - We conducted a retrospective chart review of all hemophiliacs followed by our
      pediatric hematology service from January 1, 1980 to December 31, 1989 inclusive,
      to determine the frequency and nature of their visits to our Emergency Department
      (ED). Of 36 patients studied, 26 were Factor VIII deficient (13 mild, 3 moderate,
      and 10 severe) and 10 had Factor IX deficiency (7 mild and 3 severe). No patient
      had red blood cell (RBC) antibodies or factor inhibitors. One patient was HBsAg
      positive and 4 patients were HIV positive. One hundred and twenty-six ED visits
      [98 (78%) in the 1-5 age group] occurred. Soft tissue hematomas accounted for 48%
      of total injuries, hemarthroses for 24%, and head injuries for 12%. Twelve
      patients were admitted to hospital for observation or ongoing factor replacement.
      Of 15 episodes of head injuries, 1 patient had intracranial hemorrhages on 2
      occasions, while 13 received prophylactic factor replacement and recovered
      uneventfully. Despite the availability of home factor replacement, the ED remains
      an important locus for the management of the pediatric patient with hemophilia.

PMID- 8308230
TI  - Spontaneous pneumomediastinum.
AB  - A case of spontaneous pneumomediastinum with cervical emphysema is reported.
      Spontaneous pneumomediastinum may complicate processes that decrease pulmonary
      interstitial pressure or increase intraalveolar pressure leading to alveolar
      rupture. Free air may then tract along blood vessels and decompress into the soft
      tissues of the neck. Clinical symptoms include neck and chest pain, dysphonia,
      and shortness of breath. Care is supportive unless the patient has a history of
      trauma or foreign body aspiration. Symptoms typically resolve within days.

PMID- 8308231
TI  - Ketotic hypoglycemia: a case report.
AB  - Ketotic hypoglycemia (KH) is recognized in the pediatric literature as the most
      common cause of childhood hypoglycemia. Since the first manifestation of the
      syndrome is classically that of new onset seizures, initial emergency department
      presentation is likely. We describe a representative case and emphasize the
      importance of routine serum glucose and urine ketone measurements in young
      children with new onset seizures.

PMID- 8308232
TI  - Complications of varicella: varicella-associated cerebritis in a child. Case
      report and review.
AB  - Chickenpox is a common contagious disease of childhood. Infection with varicella
      zoster virus generally follows a benign course, but complications may occur. We
      report the case of a child with chickenpox who developed diffuse cerebritis with
      significant dehydration, azotemia, elevations in transaminases, and coagulopathy.
      The neurologic complications of varicella-zoster infection are reviewed.

PMID- 8308233
TI  - Gas-fired gravity floor furnace contact burns.
AB  - Infants and toddlers are at particular risk for contact burns from the registers
      of gas-fired floor furnaces. We report 11-month-old and 12-month-old boys who
      sustained the classic grid-like pattern of burns to their skin after contracting
      the registers of gas-fired floor furnaces. The depth of these burns were judged
      to be partial thickness and healed without the application of skin grafts.
      Manufacturers must devise safe registers for gas-fired furnaces that will not
      cause contact burn injuries.

PMID- 8308234
TI  - Pediatric electrocardiography in the emergency department.
AB  - Electrocardiography can be a useful screening and diagnostic tool for children
      seen in an Emergency Department setting. This article reviews the technical
      aspects of electrocardiography in children and offers an approach to
      interpretation. Normal values for ECGs in children are presented in tabular
      format. Electrocardiographic features of several specific conditions are
      discussed.

PMID- 8308235
TI  - Bacterial meningitis in infants and children: a review.
AB  - Emergency physicians are often required to evaluate febrile infants and children
      with no obvious source of infection. Most have uncomplicated viral illnesses. It
      is imperative, however, to identify the child with potentially life-threatening
      bacterial meningitis. The clinical presentation of meningitis is variable and
      depends on many factors. These variables are discussed as well as the indications
      for lumbar puncture and guidelines for laboratory evaluation. Recommendations for
      antibiotic selection and dosages are provided. The clinical trials regarding the
      use of dexamethasone are also reviewed.

PMID- 8308236
TI  - The use of Glasgow Coma Scale in poisoning.
AB  - A 12-month prospective study was undertaken to observe current practice and to
      determine if a Glasgow Coma Scale (GCS) of 8 or less on admission is a useful
      parameter to predict the need for airway protection in poisoning. For the period
      of September 1988 to August 1989, there were 414 admissions for poisoning with 3
      fatalities (0.7%). A total of 41 patients (10%) were assessed by attending
      physicians as requiring airway protection. An initial GCS of 8 or less had a
      sensitivity of 90% and specificity of 95% for predicting the need for intubation.
      Logistic regression analysis showed an odds ratio of 0.48 for the relationship
      between GCS and intubation, significant at P < 0.001. In addition, the absence of
      a gag reflex on admission gave a sensitivity of 70% and specificity of 100% for
      predicting the need for airway protection. Further analysis showed that the
      presence or absence of a gag reflex added nothing to the GCS for the prediction
      of probability for intubation. In conclusion, an initial GCS of 8 or less was
      found to be a useful guideline for intubation. However, it should be used in
      conjunction with the clinical context.

PMID- 8308237
TI  - The incidence of wound infection following crotalid envenomation.
AB  - Many sources advocate the empiric use of antibiotics to prevent wound infection
      (WI) following crotalid (rattlesnake) envenomations. We undertook a prospective
      observational study to examine the incidence of infections following crotalid
      envenomation. We studied crotalid envenomations presenting to our institution
      with follow-up by direct examination or telephone consultation. All patients
      presenting to our institution from June 1990 to October 1991 with history and
      clinical evidence of crotalid envenomation were included in the analysis. Routine
      management of crotalid envenomation was undertaken in each case, including the
      use of antivenin, surgical debridement, and antibiotics only when indicated by
      signs and symptoms of infection. A total of 54 patients were observed during the
      study period. Twelve patients received prophylactic antibiotics begun either
      prior to transfer to our institution or following a surgical procedure, and were
      evaluated separately. Follow-up was obtained on 32 patients 7 or more days
      following envenomation. Only 1 patient from the study group developed clinical
      evidence of WI during the study period. We conclude that because of a low
      incidence of WI in this series, the routine use of prophylactic antibiotics in
      such patients may not be warranted.

PMID- 8308238
TI  - Stress fracture of the femoral neck in a long distance runner: biomechanical
      aspects.
AB  - With the rising public interest in physical fitness, emergency physicians are
      seeing an increasing number of stress fractures. Early diagnosis, followed by
      conservative management, allowed a long-distance runner with a compression type
      stress fracture of the femoral neck to return to running. The biomechanical cause
      of this injury may be related to erosion of the sole of the running shoe that
      reduced its shock absorption and increased the potential for injury.

PMID- 8308239
TI  - Emphysematous cholecystitis in an elderly woman: case report and review of the
      literature.
AB  - Cholecystitis, a frequent diagnosis in emergency departments, has been discussed
      extensively in the medical literature. We report a case of emphysematous
      cholecystitis, an unusual form of this disease process, including the classic
      radiographic findings. We also offer a review of the literature, emphasizing the
      proposed pathophysiology and the life-threatening nature of this surgical
      condition. Early recognition and surgical consultation are vital in these
      patients.

PMID- 8308240
TI  - Electric shock, Part III: Deliberately applied electric shocks and the treatment
      of electric injuries.
AB  - Earlier parts of this series have discussed the physics, pathophysiology, and
      nature of electric injury. This part will discuss deliberately applied electric
      shocks and the treatment of electric injuries. Electric shocks are deliberately
      applied to persons during electroshock therapy and with stun guns, shock batons,
      and electric cattle prods. Electric injuries, whether a complication of
      deliberate electric shock or due to accidental injury, should be treated to
      preserve cardiac and respiratory function and to prevent further tissue damage.
      Safe extrication at the scene, rapid triage, and emergency medical treatment are
      discussed.

PMID- 8308241
TI  - Alcohol-related seizures, Part II: Clinical presentation and management.
AB  - Alcoholism may be society's most devastating problem short of war and
      malnutrition. Perhaps the most complex and preplexing medical complication of
      alcoholism is alcohol-related seizures. This article is a collective review
      designed to provide emergency physicians with an overview of the topic that is
      pertinent to their clinical practice. Part 1 addressed the pathophysiology,
      differential diagnosis, and evaluation of alcohol-related seizures. Part 2
      focuses on the clinical presentation, management, and disposition. In addition, a
      classification of alcohol-related seizures is proposed.

PMID- 8308242
TI  - Cervical radiography in the emergency department: who, when, how extensive?

PMID- 8308243
TI  - Past and present standards on evaluation of patient with chest pain.

PMID- 8308244
TI  - A case that illustrates the distinct advantages of femoral nerve block.

PMID- 8308245
TI  - Objectives to direct the training of emergency medicine residents on off-service
      rotation in neurosurgery.
AB  - The off-service rotation in Neurosurgery is included in some programs training
      emergency medicine residents. It may also be offered as an elective. The
      experience on this rotation can lack opportunity and educational content if
      structured guidance is not available. We have addressed this problem by
      developing a written curricula containing subject content listing, objectives,
      and references for the Neurosurgery off-service rotation for emergency medicine
      residents. This is the 23rd in a series of objectives for off-service rotations
      for emergency medicine residents.

PMID- 8308246
TI  - The art of dealing with consultants.
AB  - This article presents guidelines for interactions with consultant physicians by
      emergency physicians. The political aspects of dealing with consultant physicians
      often are not stressed in emergency medicine training programs and little has
      been written in the emergency medicine literature on this topic. Practicing
      maintenance of good relations with consultant physicians can make work in the
      emergency department more enjoyable for all concerned, and probably contributes
      to better overall patient care.

PMID- 8308247
TI  - Cranial CT scans--emergency department utilization.
AB  - The purpose of this retrospective review was to determine high-yield criteria for
      the ordering of cranial computed tomography (CT scans) in the emergency
      department. All patients (n = 416) presenting to an adult tertiary care Emergency
      Department over a 1-year period who required an emergency CT scan were studied.
      The indications for the scan and the rate of abnormal results were headache
      (26%), seizures (17%), focal weakness (46%), acute trauma (37%), late trauma
      (22%), altered mental status (32%), coma (54%), and other (32%). The overall rate
      of abnormal scans was 39%. In conclusion, the current clinical practice of
      ordering cranial CT scans on an emergency basis seems to produce an acceptable
      level of "abnormal" results. Additional prospective studies are required to
      further define high-yield criteria and measure the impact of the "negative" scan
      on patient management.

PMID- 8308248
TI  - Localization of EGF receptors in frozen tissue sections by antibody and
      biotinylated EGF-based techniques.
AB  - We developed a sensitive EGF receptor detection method for frozen tissue sections
      using biotinylated EGF as the primary reagent. The method was directly compared
      with an immunohistochemical technique based on an anti-EGF receptor monoclonal
      antibody (MAb EGFR1) in normal human and rat tissues and in human tumors. The
      method was more sensitive than a previously published biotinylated EGF-based
      technique. In normal human tissues and in 37 of the 50 tumors, the binding
      pattern mirrored that of positive staining with EGFR1. Five further tumors showed
      weak immunoreactivity, but in these no binding of biotinylated EGF was detected.
      The remaining eight tumors were negative by both techniques. The discordant cases
      may reflect a lower level of sensitivity of the ligand-binding technique or,
      alternatively, abnormal receptors may have been expressed in these tissues. EGF
      receptors could be detected in rat liver with biotinylated EGF but not with the
      antibody, indicating the usefulness of the ligand-based technique in cross
      species studies.

PMID- 8308249
TI  - New monoclonal antibodies directed against mouse follicular dendritic cells.
AB  - The follicular dendritic cells (FDC) in B-lymphoid follicles are unique reticular
      cells that retain immune complexes on their surfaces. We developed new monoclonal
      antibodies (MAb), SKY01, 28, 41, and 49, against mouse FDC without useful cell
      markers. Immunohistochemical study of spleen and lymph node tissues from Balb/c,
      C3H, and C57BL/6 mice revealed that SKY01 and 49 were highly specific for FDC,
      whereas SKY28 and 41 reacted with other stromal components as well as FDC. On
      immunoelectron microscopy (IEM), reaction products for all MAb were localized on
      the surfaces of FDC. In ontogenetic study of Balb/c spleen, FDC precursors were
      not immunodetected with any of the MAb at 1 week after birth. The FDC that first
      appeared as immune complex-retaining cells at 2 weeks were a subpopulation of
      SKY01-, 49-, 28+, and 41+ reticular cells. At 3 weeks, FDC were positive for all
      MAb, like adult spleen. These results indicate that our MAb recognize
      differentiation antigens of FDC. Comparative immunohistochemical studies of
      spleen from athymic nude and severe combined immunodeficiency mice suggested that
      B-cells may be required for the differentiation of FDC. Consequently, these MAb
      are considered useful tools for research on FDC.

PMID- 8308250
TI  - Immunocytochemical localization of M2 muscarinic receptors in rat ventricles with
      anti-peptide antibodies.
AB  - We produced antibodies against a synthetic peptide corresponding to amino acids
      168-192 of the second extracellular loop of the M2 human muscarinic receptor in
      rabbits. In immunoblot, affinity-purified antibodies specifically recognized a
      major band of rat ventricular muscarinic receptor protein with a molecular weight
      of about 80 KD. This recognition could be blocked by pre-incubation with peptide.
      Moreover, with both light (LM) and electron microscopic (EM) immunocytochemistry
      techniques, muscarinic receptors were detected on sarcolemma and T-tubules of rat
      cardiomyocytes. In addition, immunoreactions were localized in membranes of
      capillaries. Likewise, these reactivities were abolished by pre-incubation with
      peptide. These results suggest that the antibodies against the second
      extracellular loop of human M2 muscarinic receptor could specifically recognize
      rat ventricular muscarinic receptor protein and could be a powerful tool to study
      the fate of this receptor under different pathological or physiological
      conditions.

PMID- 8308251
TI  - Simultaneous visualization of G- and F-actin in endothelial cells.
AB  - We developed site-specific fluorescent probes that permit simultaneous
      microscopic observation of G- and F-actin in bovine endothelial cells. G-actin
      distribution was visualized with fluorescein-deoxyribonuclease I (DNAse I). F
      actin was labeled with phalloidin conjugated to the new long-wavelength
      fluorophore BODIPY 581/591 (581-nm excitation, 591-nm emission), which is
      spectrally similar to Texas Red. The G-actin appeared as pervasive green
      fluorescence that was more intense in the nuclear region, where cell thickness is
      greater and stress fibers are less frequent. In addition, we observed a punctate
      fluorescein pattern around the nuclei and in other parts of the cells, suggesting
      that some G-actin is localized to small discrete sites. F-actin was observed as
      red fluorescent filaments. Unlabeled DNAse I effectively prevented staining of G
      actin by the fluorescent DNAse I conjugates. The specificity of DNAse I for G
      actin was confirmed by the presence of a single labeled band with molecular
      weight corresponding to actin in a Western blot of total cytoplasmic endothelial
      proteins reacted with biotin-DNAse I-streptavidin-alkaline phosphatase. Anti
      actin antibody, which associates with both G- and F-actin, in conjunction with
      fluorescent secondary antibody produced a pattern similar to that obtained by
      simultaneous visualization with fluorescein-DNAse I and BODIPY 581/591- or
      rhodamine-phalloidin.

PMID- 8308252
TI  - Ultrastructural immunogold localization of osteopontin in human gallbladder
      epithelial cells.
AB  - We used a post-embedding ultrastructural immunogold method to localize
      osteopontin in human gallbladder epithelial cells. This glycoprotein, originally
      described in bone but recently found to have a much wider distribution in many
      epithelia and in some mesenchymal cells, was present in the filamentous
      glycocalyx, small apical cytoplasmic smooth membrane-bound vesicles, large
      membrane-bound cytoplasmic granules, and in portions of the Golgi complex in
      gallbladder columnar epithelial cells. These findings suggest that newly
      synthesized osteopontin is packaged in Golgi-derived granules that release their
      contents by classical exocytosis from the cell surface. At least a portion of
      secreted osteopontin remains on the cell surface, where it becomes integrated
      into the filamentous glycocalyx coating the luminal surface of gallbladder
      epithelial cells.

PMID- 8308253
TI  - A protein-specific monoclonal antibody to rat liver beta 1-->4
      galactosyltransferase and its application to immunohistochemistry.
AB  - We have produced a new protein-specific monoclonal antibody (MAb) to rat liver
      beta 1-->4 galactosyltransferase. This MAb, GTL2, was selected as the most
      reactive IgG to a periodate-treated antigen. Antigen and protein specificities of
      GTL2 were verified by immunoblotting of a non-glycosylated recombinant protein of
      human galactosyltransferase and enzymatically deglycosylated rat
      galactosyltransferase. Using GTL2, an immunohistochemical study was done in rat
      liver, epididymis, and salivary glands. Intense staining was observed in Golgi
      areas of epididymal duct epithelial cells, and submandibular and sublingual
      acinar cells. Hepatocytes showed weaker staining. Immunoelectron microscopic
      observation revealed that the staining was exclusively localized in trans-Golgi
      membranes of these cells.

PMID- 8308254
TI  - Fucosylated Thomsen-Friedenreich antigen in alpha-anomeric configuration in human
      gastric surface epithelia: an allogeneic carbohydrate antigen possibly controlled
      by the Se gene.
AB  - Human gastric surface epithelial cells display the ABH blood group antigens with
      the core structure of N-acetyllactosamine (NAcLc). Their expression is under the
      control of the secretor gene Se. The Thomsen-Friedenreich (T)-antigen (Gal beta 1
      3GalNAc) is another core structure of the ABH antigens. We examined the gastric
      surface epithelial expression of T- and alpha 1-2 fucosylated T (FucT)
      histochemically with peanut agglutinin (PNA) and monoclonal antibody (MAb) MBr1,
      respectively. Eight of 24 individuals exhibited the PNA-reactive antigen (i.e., T
      expressers) and others the MBr1-reactive antigen (i.e., FucT-expressers). alpha-L
      fucosidase digestion of the FucT-positive tissues and beta-galactosidase
      digestion of the T-positive tissues, respectively, made them reactive with PNA
      and the antibody specific for GalNAc alpha-O-Ser/Thr. There was a remarkable
      correlation among reactivities with MBr1, Ulex europaeus lectin 1 (UEA1), and
      anti-Leb MAb CO-431. ABH blood group status had no correlation with this
      expression. We conclude that human gastric surface epithelial cells
      constitutionally synthesize T in alpha configuration (i.e., Gal beta 1-3GalNAc
      alpha-O-Ser/Thr) and that it was alpha 1-2 fucosylated only in the FucT
      expressers. alpha 1-2 fucosylation of T is suggested to be regulated by the Se
      gene.

PMID- 8308255
TI  - Use of computer-assisted analysis for myofiber size measurements of rat soleus
      muscles from photographed images.
AB  - Since myofiber cross-sectional area measurements are important in describing
      myofiber adaptations to physiological and pathological changes, we developed a
      reproducible method for measuring myofiber size using fluorescent stains. Several
      35-mm slides of dystrophin-, laminin-, and concanavalin A (ConA)-stained muscle
      sections were used to calculate myofiber cross-sectional areas and to compare
      different techniques and settings of an image capture system. Although variation
      in equipment settings did result in variation in myofiber area, the overall
      effect was of little practical significance (< 6%). Using midrange values for the
      settings of illumination, black level, and gain, reproducible quantitative data
      were collected and analyzed from 35-mm slides of FITC-labeled conA taken from
      atrophic, normal, and hypertrophic muscle samples. As expected, the atrophic
      muscle fibers were smaller. However, in hypertrophic muscle from compensatory
      overload, the fibers were composed of both large and small fibers. We found it
      important that the myofiber cross-sectional area measurements be expressed both
      in terms of average fiber areas and as frequency distribution histograms. In
      addition, detailed methodology of fiber area measurement must be provided.

PMID- 8308256
TI  - A comparison of heating modes in rapid fixation techniques for electron
      microscopy.
AB  - Recent studies have established that microwave irradiation during aldehyde
      fixation of electron microscopy specimens can reduce fixation times
      substantially. Similar reductions in duration of histochemical and light
      microscopy procedures have been reported. Both thermal and non-thermal effects of
      microwaves have been proposed to explain these dramatic decreases in processing
      time. Possible thermal effects include increases in fixative diffusion and
      reaction rates and increased formation of glutaraldehyde monomers. Proposed non
      thermal effects include preferential orientation of fixative molecules by the
      microwave field and other more speculative direct microwave effects. Several
      reported attempts to produce rapid fixation without temperature increase by
      cooling specimens during irradiation have produced conflicting results. If rapid
      fixation is a thermal effect, other heating modes in addition to microwave
      exposure should produce similar effects. We show that for mouse liver samples (<
      or = 1 mm3) comparable fixation can be obtained with microwave irradiation,
      conductive and convective heating in a waterbath, and resistive heating with a
      low-frequency (1 kHz) current passed through the fixative solution. We also show
      that using an efficient convective cooling method to prevent temperature increase
      during microwave exposure produces unsatisfactory fixation. These results are
      consistent with thermal mechanisms for rapid fixation.

PMID- 8308257
TI  - Pilocarpine-induced changes in the saccharide composition of the tectorial
      membrane and interdental cells of the organ of Corti: a study with gold-labeled
      lectins.
AB  - The glycoconjugates in the cytoplasm of inner ear interdental cells and those
      constituting the limbal tectorial membrane were identified by a post-embedding
      cytochemical method using low-temperature embedding in Lowicryl K4M and labeling
      with biotinylated lectins, goat anti-biotin antibody, rabbit anti-goat antibody,
      and gold-labeled protein A in control animals, and after the systemic injection
      of pilocarpine. The lectins used were ConA, PHA-E, PSA, RCA, SBA, Succ-WGA, UEA,
      and WGA. In control animals, a semiquantitive analysis of gold particles showed
      that Succ-WGA produced the strongest labeling on the tectorial membrane, followed
      by SBA, ConA, WGA, RCA, PHA-E, and PSA. The lowest values were obtained with UEA.
      The cytoplasm of the interdental cells was also labeled with all the lectins, but
      the number of particles/microns2 was lower than on the tectorial membrane. The
      concentration of gold particles on the limbal tectorial membrane in pilocarpine
      treated animals was higher than in control animals for some lectins (RCA, PSA,
      UEA) but lower for others (WGA, SBA, PHA-E, Succ-WGA). The changes in the
      labeling pattern of the cytoplasm of the interdental cells paralleled those in
      the tectorial membrane. These results demonstrate that the saccharide composition
      of the limbal tectorial membrane can be modified by systemic injection of
      pilocarpine. This action may take place through a change in either the secretion
      rate or the amount of some glycoconjugates by the interdental cells.

PMID- 8308258
TI  - Lysosomal cysteine proteinases in rat epididymis.
AB  - To examine the precise localization of lysosomal cysteine proteinases, cathepsins
      B, H, and L in rat epididymal epithelial cells, immunohistochemistry and enzyme
      assay were applied to the epididymal tissue. Granular immunodeposits for
      cathepsins B and H were detected in epididymal epithelial cells, whereas faint or
      no immunoreactivity for cathepsin L was found. Moreover, immunoreactivity for
      cathepsin B appeared mainly in principal cells and was more intense in the head
      of the epididymis than in the tail, whereas that for cathepsin H appeared in both
      principal and clear cells and was more intense in the tail than the head. By
      enzyme assay, activities of cathepsins B and H showed a similar distribution to
      that of the immunoreactivity. The cathepsin L-specific activity was distributed
      evenly in each part of the epididymis and was also detected in epididymal fluids
      obtained from the body and tail parts. By immunoblotting, proforms of cathepsins
      B, H, and L were present in the seminal fluid. The results suggest that
      cathepsins B and H are involved in the intracellular degradation system of
      epididymal epithelial cells, and proforms of cathepsins B, H, and L may be
      secreted into the epididymal duct lumen.

PMID- 8308260
TI  - Double-immunostaining method using biotin-conjugated primary antibodies from the
      same species.

PMID- 8308259
TI  - Immunogold electron microscopic localization of timothy grass (Phleum pratense)
      pollen major allergens Phl p I and Phl p V after anhydrous fixation in acrolein
      vapor.
AB  - We used the vapor phase of acrolein as an anhydrous fixative for timothy grass
      pollen in an immunogold double-labeling localization study of two different major
      allergens, Phl p I and Phl p V. More than 48 hr of fixation were needed for the
      subcellular pollen structures to be satisfactorily stabilized. The
      immunoreactivity of acrolein-fixed pollen allergens was not destroyed even after
      prolonged acrolein fixation. By immunoblotting, the two allergens differ in their
      immunological and structural characteristics. Electron microscopic localization
      traced the allergens at least partially to different subcellular pollen
      compartments.

PMID- 8308261
TI  - Fast regeneration of the olfactory nerve in goldfish: fine structure and
      behaviour.
AB  - Normal olfaction-guided behaviour in goldfish returns surprisingly fast after
      bilateral transection of the olfactory nerve (ON). In order to find correlation
      between morphological changes and behaviour we performed parallel studies on the
      behaviour of the fish and the ultrastructure of the olfactory bulb in axotomised
      fish. Signs of degeneration were most prominent between the 4th and 6th day post
      operatively. First appearance of regenerated ON fibres and terminals was noted on
      the 10th post-operative day. ON terminals became frequent again two weeks after
      the operation. This supports earlier suppositions that morphological regeneration
      plays a crucial role in the fast and complete restoration of olfaction-guided
      behaviour.

PMID- 8308262
TI  - [Development of telencephalon in Agapornis roseicollis Vieillot (Psittacidae) and
      its relationship to the evolution of the telencephalon in vertebrates].
AB  - 1. The cerebral anlage of Agapornis roseicollis was investigated in serially cut
      slices during the developmental stages before hatching (day 3-day 20) by light
      microscopical quantitative and qualitative methods. 2. During earlier stages of
      development, the brain anlage is divided in three dorsally and four ventrally
      situated, longitudinally oriented matrix zones (D1-D3, V1-V4 according to
      Kuhlenbeck). In this developing system, mainly the lateral part of the
      telencephalic wall including its dorsal extension is considered to establish
      special importance for the further ontogenetic development. 3. The quite simple
      structure of the epistriatum in Reptils occurs as the neo-hyperstriatum-complex
      in Birds; likewise, deriving from the neocortex primitivus in Reptils, in
      Mammalia this part obviously develops to the more and more expanding neocortex as
      can be followed from lower mammalia species up to the highly developed Primates.
      According to the first main criterion of Remane, the homology of these parts of
      the brain in different vertebrates is most evident because these brain parts
      occupy exactly the same position in the brain anlage of early embryonal stages.
      4. In Reptils, the neocortex primitivus appears as the last during ontogenetic
      development. Likewise in Birds, the neohyperstriatum-complex that is homologeous
      to the neocortex in Mammalia, differentiates during the final stages. These facts
      again emphasize the homology of these structures. 5. Further evidence for
      homology is obtained by the observation that in Agapornides the primordium of the
      neo-hyperstriatumcomplex contains migrating matrix cells columns, which also in
      Mammalia arrange into the same manner. Moreover, the transient and
      heterochronuous occurrence of cell layers at the outer surface of the brain
      anlage reminds to the development of palaeocortex and neocortex in Reptils and
      Mammalia. 6. From the point of view of evolution biology, the process of the
      progressive evolution is considered to be based on the step by step addition of
      tiny new structure-function-units to the already present morphology going along
      with a full structural and functional integration of the added, thus to achive
      the new quality. This so-called "Additive Morphogenesis" was effective during
      millions of years, consisting of such microevolutionary processes, and finally
      caused the "Gestaltungswandel", the ever changing evolving variety of bodily
      forms (and functions) that is recapitulated during individual species
      ontogenesis.

PMID- 8308263
TI  - Induced hydrocephalus in postnatal rats following an intracerebral injection of
      ricin.
AB  - A single injection of peroxidase-labelled Ricinus communis agglutinin (RCA-HRP)
      was given intracerebrally in 5-day old postnatal rats to determine its effects on
      neural tissues. The rats were sacrificed at various time intervals ranging from 1
      hour to 8 weeks after the injection. 5 days after the injection, the lateral
      ventricle ipsilateral to the injection was progressively enlarged. The size of
      the ventricle continued to expand so that 10-15 days after the injection the
      ventricle on the contralateral side was also affected. In longer surviving rats,
      i.e 3-8 weeks after the injection, both the ventricles were extremely dilated
      resulting in the thinning of the cerebral cortex. Scanning electron microscopy of
      the dilated ventricles showed signs of disruption of the ependyma in some
      regions. A number of cells including macrophages, neurons, glioblasts, astrocytes
      and oligodendrocytes were present on the ependyma. Their identification was
      confirmed by scanning- and transmission electron microscopy. Transmission
      electron microscopy of the cerebral cortex subjacent to the dilated ventricles
      showed the presence of many degenerating neurons, 2-5 hours after the injection
      of RCA-HRP. The neurons displayed typical features of degeneration, i.e.
      displacement of nucleus, dilatation of cisternae of rough endoplasmic reticulum,
      and swelling and disintegration of mitochondria. In conclusion, following a
      single intracerebral injection of RCA-HRP, drastic neuronal degeneration was
      elicited near the site of injection and this resulted in the dilatation of the
      lateral ventricles similar to hydrocephalus.

PMID- 8308264
TI  - The perivascular fibrotic reaction in rat brain in the late period after
      experimental clinical death. II. Precapillary vessels.
AB  - The aim of the study was to investigate the area surrounding precapillary vessels
      in the temporal cortex of rat-brains. The material consisted of animals that
      survived a 10-minute cardiac arrest and then lived on for 10 to 12 months. In the
      specimens that survived 10 month we observed dilatation of the pericapillary
      space pervaded with unidentified cells surrounded by multiple collagen fibrils.
      In the close vicinity of these vessels we often discerned cells participating in
      the process of phagocytosis. Smooth muscle cells held numerous pinocytic vesicles
      which contained microfibrillar material. Collagen fibrils were also discerned
      beneath their basement membrane. In the animals that survived 12 months in many
      cases the spaces between blood vessel mural myocytes and brain cells were filled
      with numerous collagen fibrils. In some cases these fibrils formed bridge-like
      structures between vessel walls and surrounding nerve cells. These compartments
      were often accompanied by brain phagocytes, the cytoplasm of which contained
      single fibres or bundles of collagen located in the close proximity of the
      phagolysosomes. We discussed the role of myocytes, myofibroblasts and phagocytes
      in the production of reparative collagen following the destruction of
      precapillary vessels and brain continuity.

PMID- 8308265
TI  - EM study on Phaseolus vulgaris lectin labelled terminals of rotundal fibers and
      on GABA immunogold stained structures in chicken ectostriatum centrale.
AB  - After having iontophoretically injected Phaseolus vulgaris Lectin into nucleus
      rotundus, labelled terminals were examined in ectostriatum centrale by EM. These
      terminals contained round synaptic vesicles. They were observed earlier by Golgi
      method and proved to be of rotundal origin by Phaseolus Lectin tracing method.
      The labelled terminals establish synapses, on large and small dendritic truncs of
      projection and local circuit neurons, and also contact spines and dendritic
      processes of projection neurons. They were observed on soma of GABA
      immunopositive local circuit neurons, and also on dendrites. Some observations
      completed the already known data on fine structure of the chicken ectostriatum
      centrale.

PMID- 8308266
TI  - Differential activation of the cortical visual areas in visually deprived rats.
AB  - The distribution of Fos-like protein, suggested to be a sensitive marker for
      neuronal activity, was studied in the visual cortex of 60 days old rats which
      were either blind congenitally and had their eyelids remained closed, or were
      born normally in terms of their visual apparatus but were dark reared, or were
      dark reared and exposed to light shortly before sacrifice, or were normal and
      reared in normal ambient light. Regardless of the primary cause, light
      deprivation produced a striking increase in Fos immunoreactivity, mainly in
      visual areas 17 and 18 a, with Fos-positive cells predominantly located in
      laminae IV and VI. Exposure of dark reared rats to ambient light further enhanced
      Fos immunoreactivity but it did not change the distribution pattern of Fos
      immunoreactive neurons.

PMID- 8308267
TI  - A light-microscopic study on pineal organ structure and innervation in the
      catfish, Heteropneustes fossilis.
AB  - In Heteropneustes fossilis, the pineal organ consists of a long hollow stalk (PS)
      and an elongate spindle-shaped end vesicle (EV) which lies beneath a highly
      specialized window. The EV is formed of a dorsal thin and ventral thick
      parenchymal layer, separated by a lumen and contains photoreceptor, supportive
      and ganglion cells. The numerous photoreceptor cells are characterized by apical
      processes which are AF- and PAS-positive. In Holmes' silver preparation, the
      apical processes showed parallel silver-positive lamellae embedded in luxol fast
      blue coagulum. The supportive cells are ependymal or glial-like. The ganglion
      cells or neurons are bipolar or multipolar with prominent dendrites and long,
      beaded and occasionally branched axonal processes. The neurons are strongly
      acetylcholinesterase (AChE)-positive. The EV also showed strong toluidine blue
      positive mast cells and AF-positive granules and fibres. The PS is composed of
      the same cellular structures. The neurons are small and AChE-positive. Pineal
      tract fibres were arranged into dorsal and ventral bundles in the middle and
      proximal regions of the PS. Silver-positive neurons were found among or close to
      the pineal tracts. The pineal tract fibres innervate the habenular commissure,
      habenular nucleus, subcommissural organ, posterior commissure and pretectum, and
      are AChE-positive. At the origin of the stalk, the pineal tract fibres were seen
      to project into the ventricle and innervate the subcommissural organ both
      supraependymally and transependymally.

PMID- 8308268
TI  - Colloid cyst of the third ventricle with XYY-syndrome.
AB  - Case presentation of an intra-uterine diagnosed third ventricle colloid cyst in a
      male with XYY-Syndrom. The inner cellular cover of cyst was composed by flat or
      cuboidal to columnar epithelium, which beared cilia in some areas. Other cells of
      the inner cover showed protrusions of cytoplasm, which extended into the cyst
      cavity. The cyst wall showed loosely arranged fibrous connective tissue, some
      Plasmocytes, and a few cells with granulated plasma. The histogenesis of this
      cyst was suggested immunohistologically from primitive neuroepithelial
      structures. According to sonographic findings an intra-uterine diagnosed
      intracerebral cyst should be a cause to search other malformations.

PMID- 8308269
TI  - Isolation of CD3-, CD4-, CD8-, IL-2R+ thymocyte precursors by panning.
AB  - We present a panning method for isolation of thymocytes that are CD3-, CD4-, CD8-
      and IL-2R+. These cells have been isolated by positive selection on dishes coated
      with 7D4 antibody followed by treatment with biotinylated 145-2C11, GK1.5, and 53
      6.7 antibodies and negative selection on avidin coated dishes.

PMID- 8308270
TI  - Enhanced IgG production in eRDF media with and without serum. A comparative
      study.
AB  - The performance of three basal media RPMI, DMEM/F12 (DF) and eRDF (enhanced RDF,
      RPMI:DMEM:F12 in 2:1:1) were evaluated in cultures with and without serum with
      respect to cell proliferation, metabolism and monoclonal antibody (Mab)
      productivity. Based on the ease of adaptation, growth rate, maximum cell density
      and Mab production, the media were ranked as follows: eRDF > DF > RPMI. This was
      true for serum-free (SF) and serum supplemented (SS) media in static and shaker
      cultures. Growth performances in static and shaker cultures were consistently 20
      50% lower in all three SF media compared to the corresponding SS conditions.
      Antibody titres in DF/SF and RPMI/SF cultures, irrespective of the culture
      condition, were generally similar or slightly lower than their SS counterparts.
      However, eRDF/SF medium yielded a much higher Mab titre (193 mg l-1) compared to
      eRDF/SS medium (145 mg l-1). This was also six times higher than the lowest titre
      of 30 mg l-1 in RPMI/SF medium. Hybridomas in eRDF/SF were further adapted to
      media without bovine serum albumin (eRDF/SF-BSA). Maximum cell densities in these
      cultures improved with scale up, from 1.1 x 10(6) ml-1 in static, to 1.9 x 10(6)
      ml-1 in shaker flasks, to 2.5 x 10(6) ml-1 in bioreactors. However, Ig levels
      remained between 100-130 mg l-1 which were much lower than in eRDF/SF medium.
      Thus BSA appears to be necessary for Ig production. The manufacturing cost
      (excluding purification) of Ig using eRDF was calculated to be between 17-50% of
      the price of the other two media and therefore this is regarded as the best
      medium for Ig production.

PMID- 8308271
TI  - A method for in vitro synthesis of unglycosylated recombinant complement
      component C9.
AB  - A method for in vitro synthesis of human complement component C9 has been
      established in order to generate unglycosylated normal and mutant proteins
      without the need to sub-clone. One or two step polymerase chain reaction (PCR)
      was used to add the T7 RNA polymerase promoter and introduce multiple mutations
      within the cDNA. The cDNA was then transcribed by T7 RNA polymerase and the mRNA
      translated in a rabbit reticulocyte lysate or wheat germ system. Successful
      synthesis was confirmed by: the correct size of PCR product DNA on agarose gel
      electrophoresis, incorporation of [alpha-32P]UTP into mRNA, and formation of
      [35S]methionine-labelled protein of the correct molecular mass for full length
      C9. The wheat germ extract generated up to 1.5 micrograms of recombinant C9. This
      unglycosylated C9 had at least 10% of the haemolytic activity of native C9.
      Unglycosylated C9 polymerised more readily than the native protein. This
      spontaneous polymerisation was increased by removal of the first 23 amino acids
      or mutating two cysteines at positions 33 and 36. This therefore provides a rapid
      method for screening the effect of multiple mutations on the biological activity
      and polymerisation of pore forming proteins.

PMID- 8308272
TI  - The use of peptide ELISA in determining malaria endemicity.
AB  - A study was undertaken with the objective to find out whether a reliable
      transmission index could be established by a simple peptide ELISA. This would be
      important to evaluate the success of the bioenvironmental malaria control
      programmes implemented in endemic areas like the Haldwani and Shankargarh
      districts of Uttar Pradesh, India. We have estimated antimalarial antibodies
      against three synthetic peptides derived from blood stage antigens of Plasmodium
      falciparum and against P. falciparum crude antigen by enzyme-linked immunosorbent
      assay (ELISA), in children and adults. We have found that while all the peptides
      react with serum antibodies, as does the whole crude blood stage antigen, a
      nonapeptide from RESA antigen gave the most uniform results. Our results suggest
      that synthetic peptides, which are easy to obtain and can be fully characterized,
      may offer a simple way to measure malaria endemicity.

PMID- 8308273
TI  - Large-scale expansion in interleukin-2 of tumor-infiltrating lymphocytes from
      patients with ovarian carcinoma for adoptive immunotherapy.
AB  - Tumor infiltrating lymphocytes (TIL) from malignant ascites or solid tumor
      specimens obtained from patients with ovarian carcinoma were expanded to large
      numbers in vitro (10(10)-10(11)) by a four-step method using AIM V medium and low
      concentrations of recombinant interleukin-2 (rIL-2). The expansion procedure
      employed 24-well culture plates, T-flasks, polyolefin gas-permeable bags (PGPB),
      and an artificial capillary culture system (ACCS). The mean number of mononuclear
      leukocytes introduced into the 24-well plates was 16.5 +/- 4.2 x 10(6) cells. TIL
      from a total of 16 patients were expanded only through the first three steps of
      the process (24-well-plates, T-flasks, and PGPB) with an overall expansion of 255
      +/- 99 fold and mean duration of 27.4 +/- 2.2 days. TIL from 9 of 16 patients
      were expanded further through the fourth step (ACCS) of the expansion method. The
      cumulative fold-expansion in nine patients was 8044 +/- 4807 (mean +/- SEM), the
      median was 2876 and the mean expansion time was 47.1 +/- 4.7 days. TIL from seven
      additional patients did not grow in rIL-2. Six of these 7 patients received
      chemotherapy at least four weeks before the specimens were collected. Two ACCS
      were used in parallel to facilitate expansion of TIL. Viable rIL-2-expanded TIL
      in the range of 1 x 10(10)-1 x 10(11) were recovered from the two ACCS, a number
      sufficient for adoptive immunotherapy of patients with ovarian carcinoma. The rIL
      2-expanded TIL were predominantly CD3+ CD4+ CD8- alpha beta TCR+, although CD3+
      CD4- CD8+ alpha beta TCR+ T cell lines were obtained from certain patients. An
      increase (43 +/- 8 vs 75 +/- 13; P = 0.05) in the proportion of CD4+ cells was
      observed over the duration of the four expansion steps. However, CD8+ TIL-derived
      T cells lines were also expanded in the ACCS. The four-step expansion method
      described here has several significant advantages over existing techniques. It
      requires substantially less personnel, equipment and space and the risk of
      contamination during expansion of the cultures is decreased. These results
      demonstrate that the four-step method described here can be effectively used for
      the large-scale expansion of ovarian TIL for the treatment of patients with
      ovarian carcinoma by adoptive immunotherapy.

PMID- 8308274
TI  - A dot-immunobinding assay for the demonstration of soluble Fc gamma receptors.
AB  - We have developed a sensitive dot-immunobinding assay to demonstrate and
      characterize the functional activity of soluble Fc gamma receptors (FcR). Samples
      containing soluble FcR were immobilized on a nitrocellulose membrane. Immune
      complexes of horseradish peroxidase and rabbit IgG antibodies to horseradish
      peroxidase (HRP) were allowed to react with nitrocellulose-bound FcR, and the
      immune complexes were visualized by HRP developer. The intensity of the grey dots
      reflected the amount of immune complex bound. Binding of immune complexes to
      placental extract containing soluble FcR was inhibited completely by IgG and Fc
      fragments, but not by F(ab')2 fragments, IgA and IgM. The method was used to
      characterize the subclass specificity of solubilized placental FcR. Human Fc
      fragments, and intact IgG1 and IgG3 proteins inhibited the binding whereas
      preparations of F(ab')2, IgG2 and IgG4 did not. In conclusion, the dot
      immunobinding assay described is a rapid and simple method for the demonstration
      and characterization of functionally active soluble FcR.

PMID- 8308275
TI  - Enzyme immunoassay detection of induction of MHC class I expression by synthetic
      peptides from the E6 and E7 regions of human papillomavirus type 16.
AB  - Viral antigens are presented to cytotoxic T cells (CTL) in the form of
      endogenously processed peptides bound to major histocompatibility complex (MHC)
      class I molecules. A variety of different methods for measuring the ability of
      peptides to bind to MHC class I have been described. Several of these methods use
      the murine lymphoma mutant cell line RMA-S, which has a peptide loading defect
      resulting in a low expression of surface class I molecules that can be
      upregulated if a synthetic binding peptide with class I binding ability is added
      to the culture medium. In order to be able to screen for peptides with MHC class
      I binding ability, we developed an enzyme immunoassay for quantitation of MHC
      class I expression on RMA-S cells. 107 synthetic peptides derived from the E6 and
      E7 regions of human papillomavirus type 16 were screened for ability to
      upregulate class I expression of Kb or Db alleles. At a concentration of about
      300 microM, 9/107 peptides were found to restore expression of Db to equal or
      greater levels than found in the RMA-S parental cell line RMA, while 35/107
      peptides were able to partially restore Db expression. For Kb, 16/107 peptides
      were able to restore expression and 40/107 peptides induced partial upregulation.
      Titration experiments showed that upregulation of class I expression by these
      peptides was dependent on a high peptide concentration, since consistent
      upregulation could in no case be detected at concentrations below 10 microM. The
      class I binding peptides identified in the present study may be useful in the
      study of the CTL response to HPV in mouse model systems. The enzyme immunoassay
      used could facilitate the rapid search for class I binding peptides.

PMID- 8308276
TI  - Purification and immunochemical characterization of a natural human polyreactive
      monoclonal IgM antibody.
AB  - In vitro and in vivo experiments to explain the function of natural polyreactive
      antibodies, usually of the IgM isotype, require large amounts of purified
      antibodies. We have developed a two-step purification procedure using a human
      natural polyreactive monoclonal IgM antibody (CB03). This combines hydrophobic
      interaction chromatography on phenyl-Superose and gel filtration over Superose 12
      and readily permits scaling-up to isolate mg to g amounts of antibody. Retention
      of the CB03 antibody during gel filtration by precipitation and interaction with
      the gel matrix was overcome by the addition of 10 mM 3-[(3-cholamidopropyl)
      dimethylammonio]-1-propanesulfonate. The yield of purified antibody was 34% and
      Fab fragments were obtained from the purified CB03 antibody by hot tryptic
      digestion (yield, 68% of theoretical amount). In an enzyme-linked immunosorbent
      assay, Fab and complete antibody had similar reaction patterns with different
      antigens.

PMID- 8308277
TI  - The standard chi 2 test used in limiting dilution assays is insufficient for
      estimating the goodness-of-fit to the single-hit Poisson model.
AB  - Limiting dilution analysis is a common technique that is used in immunology to
      estimate accurately the frequency of cells possessing a wide variety of
      functional activities, such as growth, cytotoxicity and production of
      lymphokines. In the literature, most experiments are fit well by the single-hit
      Poisson model (SHPM), which assumes that only one cell of one defined cell subset
      is necessary for a positive response. This is somewhat surprising since other
      models such as multi-hit or multi-target models that involve the interaction of
      one or more cells from one or more cell subpopulations for generating or
      inhibiting a positive response are conceivable. Since the validity of the SHPM is
      usually investigated by performing a standard chi 2 test, based on the number of
      observed and expected positive and negative responses, we questioned here the
      efficiency of this test in comparison with other validity tests for the SHPM, the
      log likelihood test derived by Cox, and the modified Weibull plot tests, the
      principles of which are entirely different from that of the standard chi 2 test.
      We used the following theoretical approach. First, we generated artificial data
      corresponding to multi-hit and multi-target models. Second, considering that
      these data were derived from real experiments, we calculated the frequency of the
      desired cell subset according to the SHPM using the maximum likelihood method.
      Then, the goodness-of-fit of these data with the SHPM was evaluated. The log
      likelihood test and the modified Weibull plot tests rejected the SHPM hypothesis,
      while the standard chi 2 test did not. Thus, the standard chi 2 test is unable to
      discriminate sensitively between the SHPM and more complicated (non-single-hit)
      Poisson models. We concluded that the results of limiting dilution studies
      published thus far must be evaluated with caution. The statistical tests
      presented here should be routinely applied for each limiting dilution experiment.

PMID- 8308278
TI  - DMISA (dissociated membrane immunosorbent assay), a new ELISA technique performed
      with blotted samples.
AB  - This study describes the use of electrophoretically purified antigens blotted
      onto nitrocellulose, as solid phase antigens for enzyme-linked immunosorbent
      assays. This procedure is called DMISA, for dissociated membrane immunosorbent
      assay. The method is illustrated using immunoblotted antigens of Dactylis
      glomerata grass pollen extract. The band of interest was located on a print of
      nitrocellulose by light staining (India ink), then the corresponding strip of
      nitrocellulose was cut out. Immediately after its solubilization in
      ethyleneglycol monomethyl ether, the antigen coated nitrocellulose was
      precipitated by the addition of buffer. In this way the bulk of the antigen
      remained bound to the membrane. The resulting suspension was carefully washed,
      and used as a solid phase antigen in an enzyme-linked immunosorbent assay. Two
      different electrophoretic methods were used to separate the Dactylis glomerata
      antigens. We compared the results obtained with classical immunoblot and with
      DMISA, for IgG4 and IgE quantification using sera from patients allergic to D.
      glomerata and purified blotted antigens present at the nanogram level.

PMID- 8308279
TI  - Comparison of a lysed whole blood method to purified cell preparations for
      lymphocyte immunophenotyping: differences between healthy controls and HIV
      positive specimens.
AB  - Although the majority of clinical laboratories now use a lysed whole blood (LWB)
      method for routine immunophenotyping, researchers wishing to perform other types
      of studies with lymphocytes from HIV+ patients may still need to use purified
      cell preparations, such as peripheral blood mononuclear cells (PBMC). A
      comparison study of the two methods was performed, using peripheral blood
      specimens from normal donors and from patients infected with the human
      immunodeficiency virus (HIV+). Reproducibility studies and several types of
      holding studies (both before and after specimen processing) were also performed.
      The results suggest that the two different methods of sample preparation have
      different effects upon abnormal patient specimens than those observed in healthy
      controls. Immunophenotyping results derived from the two different methods cannot
      be considered equivalent for the purposes of quantitating the presence of a
      particular type of cell.

PMID- 8308280
TI  - The separation of the granulocytes from different rat strains. A comparative
      study.
AB  - Different Percoll density gradients were used to purify granulocytes from Long
      Evans, Fischer, Sprague-Dawley, and Fischer/Long-Evans hybrid rats. Three
      different discontinuous gradient types were developed which permitted the
      separation of polymorphonuclear leukocytes (PMNLs) from the peripheral blood of
      the different rat strains. Our purification techniques were compared to each
      other in terms of purity and yield. Purities of 97.7 +/- 0.6%, 97.0 +/- 1.1%,
      96.4 +/- 1.2% and 96.7 +/- 1.1% were achieved for the granulocyte fractions of
      LE, F344, SD and FL/F1 rats, respectively. The superoxide production of the
      isolated cells was also investigated and it was established that the granulocytes
      could be activated by phorbol-12-myristate-13-acetate (PMA).

PMID- 8308281
TI  - An ELISA for the measurement of human leukemia inhibitory factor in biological
      fluids and culture supernatants.
AB  - A new monoclonal antibody-based ELISA for leukaemia inhibitory factor/human
      interleukin for DA cells (LIF/HILDA) measurements is described. The sensitivity
      (56 pg/ml after 4 h incubation, 14 pg/ml after 24 h incubation), precision (intra
      assays < 5%), reproducibility (interassay < 10%), and accuracy (recoveries,
      ranging between 98 and 119%, in several fluids) of the assay, plus its excellent
      performance in dilution tests, and the lack of interference when in the presence
      of possible cross-reactive substances guarantee accurate cytokine measurement in
      biological fluids such as serum, plasma, synovial fluid, follicular fluid, urine
      and culture supernatants. Using the assay, LIF/HILDA was measurable in
      supernatants after in vitro whole blood stimulation with phytohemagglutinin
      (PHA), OKT3, and phorbol myristate acetate (PMA) but not with lipopolysaccharide
      (LPS) or Ca ionophore. LIF/HILDA production was not measurable until after 24 h
      of culture, when cytokine levels were seen to increase linearly in the
      supernatant to reach values of up to 40 ng/ml after 96 h of culture. Finally, a
      good correlation was found (r = 0.96; p < 0.0001; y = 23.1x + 233) between the
      LIF/HILDA values obtained using the ELISA and DA-1a bioassay.

PMID- 8308282
TI  - A scanning tunnelling microscopy comparison of passive antibody adsorption and
      biotinylated antibody linkage to streptavidin on microtiter wells.
AB  - An antiferritin antibody was either, (a) passively adsorbed to microwells or (b)
      biotinylated and immobilised to streptavidin coated microwells. Scanning
      tunnelling microscope (STM) imaging of these well surfaces coated with a platinum
      (95%) carbon (5%) coating (Pt/C) conductive layer showed a randomly oriented
      array of antibodies for passive adsorption whereas for biotin-streptavidin
      immobilisation there was a more uniform and even distribution of antibodies on
      the well surface. On further incubation with ferritin STM imaging showed that for
      passive adsorption approximately 5% of the surface was functional, while for the
      biotinylated antibody it was greater than 60%. The images presented in this paper
      show graphically the loss of functionality that occurs using passive adsorption
      and, conversely, the preservation of antibody functionality using the biotin
      streptavidin linkage for antibody immobilisation. These results correlate well
      with the work of others in the field.

PMID- 8308283
TI  - A new vector for the high level expression of chimeric antibodies in myeloma
      cells.
AB  - We previously reported the expression of a mouse/human chimeric anti-ganglioside
      GD3 antibody, KM871 (IgG1,kappa) in mouse myeloma SP2/0 cells under the control
      of the ecotropic Moloney virus long terminal repeat by the co-transfection of
      chimeric heavy (H) and light (L) chain vectors (Shitara et al. (1993) Cancer
      Immunol. Immunother.). To establish an efficient and high level expression system
      for the chimeric antibody, we did comparative study on vector systems and host
      cells. An improved expression vector, named 'a tandem vector, pChi641HLGM4' was
      constructed, in which both of the chimeric H and L chain gene transcription units
      and a dihydrofolate reductase (dhfr) gene transcription unit were inserted. When
      two kinds of mouse myeloma cell lines, SP2/0 and P3U1, were used as host cells,
      frequency of the incidence of antibody-producing transfectants was markedly
      increased by the use of the tandem vector compared with the use of the mixture of
      each chimeric H vector and L chain vector. To select out appropriate host cells,
      transfection frequency and antibody production level were compared among SP2/0,
      P3U1 and rat myeloma YB2/0 cells by transfection of the tandem vector. YB2/0 cell
      was shown to have the highest potential in both the transfection frequency and
      the antibody production. Introduction of the tandem vector into YB2/0 cells and
      the subsequent amplification with 50-200 nM methotrexate gave rise to several
      clones that stably secreted 70-100 micrograms/10(6) cells per 24 h of the
      chimeric antibody. This productivity of the antibody is one of the highest levels
      which have been achieved by other investigators using transfected myeloma cells.
      Using this system it took only 2-3 months to establish the transfectant clones
      which stably produced the chimeric antibody.

PMID- 8308284
TI  - Biochemical and functional characterization of soluble form of IL-5 receptor
      alpha (sIL-5R alpha). Development of ELISA system for detection of sIL-5R alpha.
AB  - Interleukin-5 (IL-5) mediates pleiotropic functions in various types of cells
      through its specific receptor (IL-5R) which is composed of two distinct subunits,
      alpha and beta. In mice, the alpha subunit (IL-5R alpha) specifically binds IL-5
      with low affinity. The beta subunit (IL-5R beta) does not bind IL-5 by itself,
      but constructs the high affinity receptor with IL-5R alpha. We have isolated cDNA
      encoding the soluble form of IL-5R alpha (sIL-5R alpha). To elucidate the
      biochemical and functional properties of sIL-5R alpha, we developed an expression
      system for sIL-5R alpha cDNA in insect cell line Sf21 using baculovirus
      expression vector and obtained conditioned medium containing large quantities of
      mouse sIL-5R alpha. Mouse sIL-5R alpha was purified from the conditioned medium
      by using anti-IL-5R alpha mAb-coupled beads. Immunoaffinity-purified sIL-5R alpha
      with an approximate molecular mass of 42 kDa inhibited the binding of 125I
      labeled IL-5 to IL-5R. By using purified sIL-5R alpha, we prepared rabbit anti
      sIL-5R alpha antibody and developed a sandwich ELISA for detection of sIL-5R
      alpha. Significant amounts of sIL-5R alpha were detected in sera and ascitic
      fluids of mice bearing tumors (BCL1 and MOPC104E) that responded to IL-5 for DNA
      synthesis, but not in sera of normal mice. Interestingly, elevated levels of
      serum sIL-5R alpha were observed in NZB and NZW mice. The sIL-5R alpha may,
      therefore, have an immunoregulatory role in vivo.

PMID- 8308285
TI  - TNF abrogates the response of the CT.4S cell line to IL-4.

PMID- 8308286
TI  - Non-isotopic in situ detection of mRNA for interleukin-4 in archival human
      tissue.
AB  - Non-isotopic in situ hybridisation (NISH) is a rapid and sensitive method
      currently used in molecular pathology to identify DNA in fresh and archival human
      biopsies. In this study we have extended NISH technology for mRNA detection to
      include the use of digoxigenin-labelled riboprobes to localise low abundance mRNA
      for interleukin-4 in paraffin embedded material (from active inflammatory bowel
      disease). As this methodological approach makes the retrospective study of
      cytokine gene expression in archival material possible for the first time, it
      could act as a prototype for studies of cytokine involvement in various human
      diseases.

PMID- 8308287
TI  - An assay for the analysis of lymphocyte migration across cerebral endothelium in
      vitro.
AB  - We describe a recently developed assay for the analysis of leukocyte migration
      across cerebral endothelium in vitro. The endothelium is grown as monolayers on
      Goretex or Cyclopore membranes coated with extracellular matrix proteins and
      supported on inserts. This system permits the recovery and phenotyping of cells
      which migrate down through the endothelium. Using labelled lymphocytes we were
      able to differentiate four populations of cells, with differing degrees of
      mobility in the migration assay. We have compared the results from this system
      with those from conventional adhesion assays. Binding of cells to the endothelium
      is rapid, but is confined to a particular subpopulation of the applied
      lymphocytes. We have followed cell migration over 24 h in the system using normal
      and cytokine-activated endothelium and have found that whereas adhesion depends
      both on the state of lymphocyte activation and on the condition of the
      endothelium, the level of migration of stimulated lymphocytes is largely
      independent of endothelial activation. Moreover, whereas CD8+ cells bind well to
      the endothelium, it is the CD4+ cells which migrate most effectively. Comparison
      of brain and epididymal fat endothelium showed similar migration levels over 2 h,
      but migration was greater across epididymal fat endothelium at 24 h.

PMID- 8308288
TI  - Isolation of immature and mature T cell receptor complexes by lectin affinity
      chromatography.
AB  - The antigen-specific T cell receptor (TCR) is a multisubunit complex composed of
      at least six different polypeptide chains (alpha, beta, gamma, delta, epsilon,
      zeta), several of which are glycoproteins. Assembly of the TCR occurs in the
      endoplasmic reticulum (ER) and involves intermediary complexes of CD3-gamma,
      delta, epsilon proteins and TCR alpha and -beta molecules. Egress of TCR from the
      ER and transport through the Golgi apparatus is most often monitored by the
      sensitivity of TCR glycoproteins to endoglycosidase H (Endo H), an enzyme
      specific for immature oligosaccharides which have not yet been processed by Golgi
      glycosidases and glycosyltransferases. Because they are not glycosylated, the
      subcellular localization of CD3-epsilon and TCR zeta chains cannot be directly
      determined by Endo H treatment, and therefore must be inferred by association
      with glycoprotein members of the TCR complex. Thus, when both immature and mature
      TCR glycoproteins are present within a given sample, this becomes extremely
      difficult. In this report, we describe a method for the physical separation of
      immature and mature murine TCR complexes based on processing of N-linked
      carbohydrate side chains. Specifically, we report the use of wheat germ
      agglutinin-affinity matrices to separate TCR complexes which have reached the
      trans Golgi compartment of the cell from those that have not. This technique is
      rapid, sensitive, and does not affect the integrity of assembled TCR complexes.

PMID- 8308289
TI  - Rapid nonradioactive in situ hybridization for interleukin-2 mRNA with riboprobes
      generated using the polymerase chain reaction.
AB  - In situ hybridization is a technique with widespread application. However, its
      usefulness has been limited by the need for radioactive materials and the
      requirement for the DNA to be cloned onto an appropriate vector. We have utilized
      the polymerase chain reaction to directly incorporate a T7 RNA polymerase
      promoter sequence onto the cDNA for interleukin-2. Digoxigenin-labelled
      riboprobes were then synthesized using this PCR product as a template. The
      digoxigenin-labelled riboprobes were then used in non-radioactive in situ
      hybridization to detect messenger RNA for interleukin-2 in mitogen stimulated
      peripheral blood mononuclear cells. This methodology has the potential for
      widespread application in immunology and cytokine research.

PMID- 8308290
TI  - Quantitation of the receptor for urokinase plasminogen activator by enzyme-linked
      immunosorbent assay.
AB  - Binding of the urokinase plasminogen activator (uPA) to a specific cell surface
      receptor (uPAR) plays a crucial role in proteolysis during tissue remodelling and
      cancer invasion. An immunosorbent assay for the quantitation of uPAR has now been
      developed. This assay is based on two monoclonal antibodies recognizing the non
      ligand binding part of this receptor, and it detects both free and occupied uPAR,
      in contrast to ligand-binding assays used previously. In a variant of the assay,
      the occupied fraction of uPAR is selectively detected with a uPA antibody. To be
      used as a standard, a soluble variant of uPAR, suPAR, has been constructed by
      recombinant technique and the protein content of a purified suPAR standard
      preparation was determined by amino acid composition analysis. The sensitivity of
      the assay (0.6 ng uPAR/ml) is strong enough to measure uPAR in extracts of
      cultured cells and cancer tissue. Recent studies have shown that a high uPA level
      in tumor extracts is in some cancers associated with poor prognosis. The present
      assay will now allow similar prognostic studies of uPAR levels.

PMID- 8308291
TI  - The genetic engineering of monoclonal antibodies.
AB  - A number of recent technological developments have greatly facilitated the
      genetic engineering of immunoglobulins. The use of PCR has permitted the variable
      regions to be rapidly cloned either from a specific hybridoma source or as a gene
      library from non-immunised cells. The conversion of the rodent antibody into a
      humanized version is now well established. To develop these antibodies for
      clinical use has required the development of high level expression systems. For
      the expression of large multimeric glycoproteins, mammalian cell systems
      generally provide the highest levels of secreted product and therefore are the
      methods of choice for producing whole recombinant antibodies. Novel antigen
      binding units have been developed by joining the two variable domains of an
      antibody into single-chain polypeptides. Such fragments can be produced in high
      yield by secretion from E. coli raising the prospect of bulk preparation of these
      antibody fragments for the development of low-cost immunopurification and assay
      reagents. Finally, the ability to screen for antigen binding by displaying
      immunoglobulin variable regions on the surface of filamentous bacteriaphages has
      opened up the possibility of bypassing the immune system to generate novel
      antibody specificities in vitro.

PMID- 8308292
TI  - Detection of allergen- and mitogen-induced human cytokine transcripts using a
      competitive polymerase chain reaction.
AB  - Human cytokines, IL-4, IL-5, and IFN-gamma play an important role in the
      regulation of IgE synthesis and atopic diseases. In this communication, we
      describe the development of a quantitative assay of steady-state cytokine mRNAs
      (IL-4, IL-5, and IFN-gamma) from a variety of cell sources, including peripheral
      blood mononuclear cells (PBMCs) stimulated with either a mitogen (PHA) or ragweed
      pollen allergen extract, and cells from allergen-challenged inflammatory sites.
      Quantitative analysis of IL-5, IL-4 and IFN-gamma transcripts was achieved by a
      competitive reverse transcription-polymerase chain reaction (RT-PCR) technique
      using internal standard (IS) cRNAs in the presence of specific oligonucleotide
      primers. Each IS was generated from a plasmid vector containing the respective
      cytokine cDNA modified by insertion with an SV40-DNA fragment. Both test RNA and
      IS were reverse-transcribed and subjected to the 'competitive' PCR in the same
      tube. We first demonstrate the linearity and reproducibility of this technique;
      second, we apply this competitive PCR assay to analyze quantitatively the
      expression of IL-4, IL-5, and IFN-gamma transcripts in PBMCs before and after
      stimulation with PHA or crude ragweed allergen. Finally, we analyzed cells
      isolated from the lung lavage fluids of an atopic subject following allergen
      challenge, and showed a significant increase of IL-4 and IL-5 transcripts, but
      not IFN-gamma, in the allergen-challenged site when compared to the control. This
      technique of PCR quantitation provides an easy and efficient tool to study the
      expression of cytokine genes in allergic inflammatory diseases.

PMID- 8308293
TI  - Ammonium chloride exposure inhibits cytokine-mediated eosinophil survival.
AB  - To study human eosinophils, their efficient purification from peripheral blood is
      crucial. Although a number of purification procedures, including discontinuous
      Percoll and metrizamide density gradient centrifugation, have been used, it has
      been difficult to isolate eosinophils from normal donors with consistently high
      yields and purities. Recently, a new isolation technique called magnetic cell
      separation system (MACS) was reported. To evaluate this procedure, we isolated
      eosinophils from human peripheral blood using either MACS or the standard
      discontinuous Percoll density methods, and compared cellular viability,
      morphology, and response to degranulation stimuli. MACS gave a higher yield of
      eosinophils than Percoll density centrifugation; for example, 6.6 +/- 1.1 x 10(6)
      eosinophils were isolated from 20 ml of blood by MACS compared to 6.4 +/- 2.4 x
      10(6) from 120 ml by Percoll density gradient. Further, the purity of eosinophils
      isolated by MACS was 97.1 +/- 0.5% (X +/- SEM) compared to 77.8 +/- 2.9% with
      Percoll. As part of the MACS protocol, erythrocytes are lysed with either 155 mM
      ammonium chloride or hypotonic lysis. With 155 mM ammonium chloride treatment,
      the eosinophils showed a striking reduction in cytokine mediated survival due to
      interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM
      CSF), marked morphologic abnormalities and a reduced degranulation response. With
      hypotonic lysis, no differences were observed in survival and morphology between
      eosinophils purified by MACS and Percoll methods; the degranulation responses to
      stimuli were essentially the same between the two methods. Taken together, these
      observations suggest that the exposure of eosinophils to 155 mM ammonium chloride
      results in cellular damage. Therefore, MACS with hypotonic lysis is a useful
      technique to isolate eosinophils for biological study.

PMID- 8308294
TI  - A simple method for the immunocytochemical processing of large numbers of
      floating sections and its application in screening for monoclonal antibodies.
AB  - A technically simple modification of routine (non-adsorbent) multi-well plates,
      permitting the simultaneous immunocytochemical processing of hundreds of free
      floating sections is described. The adaptations consist of (1) making a 1.5 mm
      wide perforation in the bottom of each well of the multi-well plate, (2) placing
      a 6 mm wide 50 microns mesh nylon filter on the bottom of each well and (3)
      preincubating the plate with excess inert protein in order to prevent adsorption
      of protein reagents. During the incubation of the floating sections with the
      immunocytochemical reagents, the fluid is retained in the well by capillarity,
      provided the detergent concentrations within the well do not exceed 0.005% (v/v).
      The wells can be emptied simply and quickly by blotting the plate bottom with a
      piece of laboratory paper toweling: the fragile sections are gently caught on the
      filter, without the risk of loss or damage. Sections start floating again as soon
      as the next reagent is added to the well. The present method drastically reduces
      the time needed for rinsing and reagent exchange, making immunocytochemistry on
      free-floating sections feasible as a primary screening method during hybridoma
      production.

PMID- 8308295
TI  - Non-radioactive labelling and immunoprecipitation analysis of leukocyte surface
      proteins using different methods of protein biotinylation.
AB  - The biotinylation of surface proteins and the detection of immunoprecipitated
      protein(s) after transfer to nitrocellulose using chemiluminescence methods is a
      highly sensitive alternative to hazardous radioactive labelling procedures.
      Ligation of proteins using the common biotin-NHS-ester (N-hydroxysuccinimido
      biotin) is often associated with a decrease in immunoreactivity. Here a new non
      radioactive method of leukocyte surface glycoprotein labelling using biotin-LC
      hydrazide is described. This technique is based on the labelling of glycoproteins
      after mild oxidation of carbohydrate hydroxyl groups to reactive aldehydes. Flow
      cytometric and immunoprecipitation analyses of selected leukocyte markers such as
      CD3, CD26 and CD65 indicated that the alteration in immunoreactivity achieved by
      NHS-mediated biotin ligation was different from that obtained with hydrazide
      mediated biotin ligation. CD3 and CD26 immunoreactivity was diminished using NHS
      biotinylation but preserved by biotin-LC-hydrazide, whereas CD65 binding to
      monoclonal antibodies was completely abolished after treatment with biotin
      hydrazide. However, the immunoreactivity of CD13 was found to be totally
      unaffected by both NHS and hydrazide biotinylation. The combination of different
      biotinylation methods for surface protein labelling offers a viable alternative
      to radioiodination in the biochemical analysis of membrane proteins.

PMID- 8308296
TI  - Measuring CDR3 length variability in individuals during ontogeny.
AB  - The portion of the antibody sequence that contributes most to the conformation of
      the antigen-combining site is the third complementarity-determining region
      (CDR3). The CDR3 in antibody heavy chains are somatically produced by the
      rearrangement of three different immunoglobulin (Ig) gene segments, VH, D and JH,
      and are therefore highly variable in sequence and length. We have devised a
      technique for rapid analysis of CDR3 length variability from a large number of
      cDNA samples. This technique allows comparative evaluation of IgH heterogeneity
      in individuals without recourse to DNA cloning and sequencing. We also present
      data on Ig sequences from different stages of development in the amphibian,
      Xenopus laevis. Most of the larval and post-metamorphic Ig samples contained CDR3
      of 3-10 codons, two codons shorter than those of the adult CDR3, which were 5-12
      codons. Antibodies may by immunized tadpoles have been shown to be much less
      diverse than those produced by adults to the same antigen. The shorter tadpole
      CDR3 perhaps generates a more limited spectrum of antigen-combining site
      structures and, in this way, makes for a more restricted antibody repertoire.

PMID- 8308297
TI  - Effect of antibody density on the displacement kinetics of a flow immunoassay.
AB  - This study investigates the effect of antibody density on the kinetics of a solid
      phase displacement immunoassay. Conducted in flow under nonequilibrium
      conditions, the assay utilizes a monoclonal antibody to the cocaine metabolite
      benzoylecgonine, which has been immobilized onto Sepharose beads and saturated
      with fluorophore labeled antigen. Displacement of antibody-bound labeled antigen
      by non-labeled antigen occurs when sample is introduced in the buffer flow.
      Comparison of matrices coated with two different antibody densities revealed that
      the displacement efficiency is a function of the density of antibody-bound
      labeled antigen. A higher density of antibody provides a higher amount of
      displaced labeled antigen, but the displacement efficiency of the assay is
      decreased. The effect of antibody density on the immunoassay kinetics was
      analyzed using a mathematical formulation developed to characterize antibody
      antigen interactions at solid-liquid interfaces. Higher antibody density proved
      to be associated with a lower apparent dissociation rate constant. The
      implications of these results on the design of immunoassays in flow are
      discussed.

PMID- 8308298
TI  - Riboprobe expression cassettes for measuring IGF-I, beta-actin and glyceraldehyde
      3-phosphate dehydrogenase transcripts.
AB  - The development of riboprobe expression cassettes for phosphorimager-based
      quantitation of steady-state transcripts for three different genes using solution
      hybridization, RNase protection assays is described. Glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH) and beta-actin genes are widely used as reporter genes to
      estimate the amount and integrity of RNA as well as for comparing gene expression
      among different tissues. To directly compare expression of these two genes in
      lymphoid tissue and liver, cDNA fragments of beta-actin and GAPDH from both mice
      and rats were generated by RT-PCR and cloned together into pGEM1 under control of
      the T7 RNA polymerase promoter. Antisense transcripts from this fusion construct
      protected the appropriate-sized fragments of beta-actin (115 nt) and GAPDH (214
      nt) in RNA isolated from rat spleen, thymus and liver. Expression of GAPDH
      transcripts was less variable across tissues because this mRNA was only two-fold
      lower in liver as compared to either thymus or spleen, whereas expression of beta
      actin transcripts was eight-fold lower in liver than in these tissues. Two other
      riboprobe expression cassettes (IGF-I/actin) were constructed by ligating a cDNA
      fragment of mouse or rat beta-actin that would protect 115 nt to either a mouse
      or rat IGF-I genomic DNA fragment containing 182 bp of exon 4. These mouse and
      rat IGF-I/actin riboprobes were used to conclusively demonstrate that rat CSF-1
      derived bone marrow macrophages, mouse elicited peritoneal macrophages and the
      murine PU5-1R macrophage cell line synthesize abundant transcripts for both IGF-I
      and beta-actin. However, the mouse M1 progenitor myeloid cell line does not
      express RNA for IGF-I, as demonstrated by the absence of protected transcripts
      for IGF-I in the presence of abundant protected transcripts for beta-actin.
      Phosphorimager scanning of the gels revealed that macrophages of both mice and
      rats express IGF-I transcripts at a level of 60-100% of those found in liver.
      These data show that a single riboprobe can be developed to generate multigene
      antisense RNAs that can then be used to quantitatively compare IGF-I transcripts
      in macrophages and other tissues to an internal standard, with GAPDH transcripts
      being less variable among tissues than those for beta-actin. This approach should
      be broadly applicable for measuring a variety of markers of cellular activation.

PMID- 8308299
TI  - An improved MTT assay using the electron-coupling agent menadione.
AB  - A modification of the MTT based tetrazolium colorimetric assay is described.
      Using the electron-coupling agent menadione formazan formation by murine
      splenocytes and P-815 cells was significantly increased whereas dye reduction by
      macrophages was hardly influenced. These observations suggest that it should be
      possible to improve the tetrazolium based cytotoxicity assays of murine
      macrophages against cells of the syngeneic tumour cell line P-815.

PMID- 8308300
TI  - Typing of the HLA-DRB3 gene by temperature gradient gel electrophoresis.
      Prediction of the resolution of four allelic fragments by computational
      simulation of DNA melting.
AB  - Four alleles are currently recognised at the HLA-DRB3 locus (DRB3*0101,
      DRB3*0201, DRB3*0202 and DRB3*0301). We studied whether 271 bp fragments of the
      polymorphic second exon, which were prepared using the polymerase chain reaction,
      could be typed using temperature gradient gel electrophoresis. Thermal stability
      curves for the allelic DNA molecules were calculated by computer simulation and
      the results were validated experimentally. The DRB3*0201 and DRB3*0202 derived
      homoduplexes were predicted to have identical thermal stability. Thus, only three
      denaturation and relative mobility curves were obtained for the four homoduplex
      fragments DRB3*0101, DRB3*0201, DRB3*0202 and DRB3*0301. Computational analysis
      predicted that DRB3*0201 and DRB3*0202 could be distinguished by electrophoresis
      of artificially generated heteroduplexes. When verified experimentally, the
      results of the theoretical analyses were confirmed. We conclude, that
      computational simulation of the melting behaviour of DNA molecules permits the
      resolution of allelic sequences to be predicted by temperature gradient gel
      electrophoresis. We also demonstrate that temperature gradient gel
      electrophoresis is a powerful tool for the assessment of HLA genotypes. It may
      have wide application in transplantation immunology and in the study of disease
      associations of allelic variation at the HLA loci.

PMID- 8308301
TI  - Simultaneous measurement of natural killer cell cytotoxicity against each of
      three different target cell lines.
AB  - A time-resolved fluorometric assay for the simultaneous measurement of natural
      killer cell activity against three different lanthanide
      diethylenetriaminopentaacetate (LaDTPA) labelled target cell lines is described.
      The target cell line K-562 was labelled with SmDTPA, the cell line Molt with
      TbDTPA and the cell line Raji with EuDTPA. After co-incubation of the three
      target cell lines with effector cells the fluorescence of the lanthanides
      released from the lysed target cells was measured in an enhancer solution in
      which they formed highly fluorescent complexes. It was possible to differentiate
      the specific release from the three target cell lines because the emission lines
      of the europium, samarium and terbium complexes formed in the enhancer solution
      are well separated from each other. The autofluorescence from culture media
      supplemented with serum was avoided by the use of time-resolved fluorometry. The
      results show that applying fluorometry based on the combination of spectral and
      temporal resolution to natural killer cell assays, makes possible the
      simultaneous determination of lysis in up to three target cell lines in complex
      culture medium.

PMID- 8308302
TI  - Identification of a higher molecular weight protein that shows apparent cross
      reactivity with anti-p21ras monoclonal antibodies on western blots.
AB  - We have characterized the immune cross-reactivity of several commercially
      available monoclonal antibodies prepared against the p21ras proteins and used in
      Western blotting experiments against human tissue homogenates. Under optimal
      conditions, only two bands were observed on Western blots. One of these
      comigrated with control p21ras protein. A second protein of apparent mobility
      corresponding to approximately 54 kDa was also observed with all four monoclonal
      antibodies tested. Protein sequencing by automated Edman degradation indicates
      that the 54 kDa species corresponds to human immunoglobulin heavy chain. Under
      suboptimal conditions, another high molecular weight species of apparent mobility
      65 kDa was also observed to cross-react with some of the monoclonal antibodies
      tested. This 65 kDa species was identified by protein sequencing as human serum
      albumin. Coomassie blue staining of SDS-polyacrylamide gels indicates that serum
      albumin is a major contaminant of many surgically obtained human tissue samples,
      while p21ras and immunoglobulin heavy chain are present at much lower
      concentrations. These results may be of significance when using monoclonal
      antibodies to determine p21ras levels of whole tissue homogenates by dot-blot,
      slot-blot or microplate assays.

PMID- 8308303
TI  - Ability of 'OptiLyse' lysing/fixing reagents to inactivate HIV-infected H9 cells
      in whole blood.

PMID- 8308304
TI  - Public health and health for all by the year 2000 AD.

PMID- 8308305
TI  - Accountability of medical professionals.

PMID- 8308306
TI  - Serological study of human toxoplasmosis in Calcutta.
AB  - A total of 248 randomly selected subjects from urban, semiurban and rural areas
      of Calcutta was studied serologically for the prevalence of antibody to
      Toxoplasma gondii using latex agglutination technique. Fifty-nine (23.79%) out of
      these 248 subjects were found to possess anti-toxoplasma antibody. Seropositivity
      was found to be higher in females (25%) as compared to males (22.32%). Agewise
      highest positivity (30.5%) for toxoplasma antibody was observed in the third
      decade and lowest in the first decade of life, though all the age groups were
      involved by this protozoal infection. Sexwise distribution of anti-toxoplasma
      antibody showed highest positivity rate in the third decade in males and in the
      fourth decade in females. Twenty-five per cent of the subjects had history of
      contact with cat and/or soil and most of the subjects belonged to the middle and
      low income groups.

PMID- 8308307
TI  - A field trial of Billings' ovulation method for spacing and limitation of birth.
AB  - In spite of constant efforts by health and social workers, existing family
      planning measures are not used by a vast majority of eligible couples. This is
      because of the fear that the method may affect their health and happiness.
      Billings' ovulation method is based on the scientific observation that by noting
      the changes in cervical mucus, which is clear, slippery and copious in
      periovulatory period, it is possible to prevent pregnancy by avoiding intercourse
      during this period. As this method does not require the use of drugs or devices
      it was decided to promote this method in the urban areas and slums of Patna,
      Bihar where couples were not using other methods. This is not a comparative study
      of the cost-effectiveness of Billings' ovulation method versus other
      contraceptive measures at all. An analysis of 501 cases (267 in urban and 234 in
      slums) over a period of 2 1/2 years has been presented and it is gratifying to
      note that the couples from all religions and strata of the society (nearly 47%
      were slum dwellers) agreed to continue this method.

PMID- 8308308
TI  - Non-articular pain.

PMID- 8308309
TI  - Post-traumatic hypopituitarism.

PMID- 8308310
TI  - Future of health care in the changing paradigm of human health.

PMID- 8308311
TI  - Ectopic pregnancy and the various determinant factors.

PMID- 8308312
TI  - Pattern of D-xylose excretion test in kala-azar patients.

PMID- 8308313
TI  - Human microsporidiosis.

PMID- 8308314
TI  - Heterogeneity in expression of lipopolysaccharides by strains of Escherichia coli
      O157.
AB  - A total of 47 strains of Escherichia coli belonging to serogroup O157 were
      examined for the expression of long-chain lipopolysaccharide (LPS) by means of
      SDS-PAGE and silver staining. Strains belonged to 10 different flagellar (H)
      types or did not express flagella. Nine strains carried genes encoding Vero
      cytotoxin (VT). Strains of E. coli O157 expressed one of three LPS SDS-PAGE
      profiles designated A, B and C. Strains expressing profile A belonged to H-types
      6 and 19, while those expressing LPS profile B belonged to H-types 2, 16, 20, 39,
      42 and 45. Strains of E. coli expressing profile C belonged to H-types 7 and 8;
      strains producing VT expressed LPS profile C only, although not all strains with
      H-types 7 and 8 carried genes for VT. Regardless of H-type or the LPS profile
      expressed, serum antibodies produced by patients infected with strains of E. coli
      belonging to serogroup O157 would be detected by serological tests.

PMID- 8308315
TI  - Septicaemia in patients with and without AIDS at Westminster Hospital, London.
AB  - The types of organism causing septicaemia in patients with AIDS and without AIDS
      at Westminster Hospital were examined prospectively over a period of 2 years
      (1990-1991). Altogether 417 episodes of septicaemia were diagnosed, 148 (35%) of
      which were in patients with AIDS. Of septicaemias in patients with AIDS, 53 (36%)
      were caused by mycobacteria. Non-mycobacterial septicaemias were associated with
      IV access devices in 58 (61%) of patients with AIDS and in 50 (19%) of those
      without AIDS. Gram-negative organisms were responsible for septicaemia associated
      with IV access devices in 16 (28%) of 58 patients with AIDS and in 8 (16%) of 50
      patients without AIDS. Non-typhoidal Salmonella species or Shigella species
      caused 13 (31%) of 42 episodes of septicaemia caused by Gram-negative organisms
      in patients with AIDS. These findings have influenced the strategy for empirical
      therapy of septicaemia in patients with AIDS at Westminster Hospital.

PMID- 8308316
TI  - Measles, mumps and rubella immunisation in children at risk of infection with
      human immunodeficiency virus.
AB  - A retrospective serological study of 81 children at risk of HIV (II HIV-infected,
      70 HIV-negative) was performed to assess susceptibility to measles, mumps and
      rubella and response to measles, mumps and rubella (MMR) immunisation. There was
      no difference in the initial serological response between the HIV-infected and
      HIV-negative children. Repeat serology should be performed on HIV-infected
      children as during follow-up antibodies may be lost. Reimmunisation should be
      considered for the seronegative.

PMID- 8308317
TI  - Immunity to tetanus in United Kingdom populations.
AB  - As tetanus, a totally preventable disease, is still encountered in the older age
      group in England and Wales, a study was carried out to assess the state of
      immunity to the disease in the elderly population. These levels were compared to
      those in recruits and service personnel in the Army. Elderly patients with
      underlying disease had lower levels than the elderly who were healthy. When
      compared with recruit population the elderly group had significantly lower levels
      of antibody. If tetanus is to be eliminated, an effective programme of
      immunisation extending throughout life must be ensured.

PMID- 8308318
TI  - The effects of electric current on bacteria colonising intravenous catheters.
AB  - The effect of a direct electric current (10 microA) on the growth of
      Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella
      pneumoniae and Proteus mirabilis was investigated. When the ends of negatively
      charged intravascular catheters were placed in nutrient agar seeded with
      bacteria, circular zones of inhibition of bacterial growth were observed around
      the catheters. The zones ranged from 6 to 16 mm in diameter according to the
      organism under test. Zones of inhibition were not produced around positively
      charged catheters. Bacteria colonising the surfaces of catheters were similarly
      affected by the application of a 10 microA electric current. A negative electric
      current applied to colonised catheters for 4 to 24 h significantly reduced the
      number of adherent viable organisms as compared to controls. The results
      demonstrated that a constant electric current of low amperage might be used to
      reduce bacterial colonisation of intravascular catheters. This may offer a novel
      means of protecting catheters and other prosthetic devices from associated sepsis
      in vivo.

PMID- 8308319
TI  - Rapid detection of enteric adenoviruses by means of the polymerase chain
      reaction.
AB  - A simple polymerase chain reaction (PCR) assay for detecting enteric adenoviruses
      (Ads 40 and 41) in faecal extracts is described. A pair of PCR primers designed
      to hybridise to the EIB genes of Ad40 and 41 was found to amplify only Ad40 and
      41 DNA but not EIB genes or viral DNA from representative numbers of the other
      human adenovirus subgenera. The PCR assay was tested on a panel of 10 faecal
      extracts, all of which contained adenovirus particles (as judged by electron
      microscopy) but only four of which proved amenable to serotyping. Extracts in
      which enteric adenoviruses had been detected serologically yielded positive
      results in the PCR assay. These results suggest that this PCR assay may be useful
      for detecting enteric adenoviruses in clinical samples.

PMID- 8308320
TI  - Meningitis due to penicillin resistant Streptococcus pneumoniae occurring in a
      patient on long term ampicillin prophylaxis.
AB  - A patient with persistent dural fistula, CSF rhinorrhoea and a history of
      recurrent bacterial meningitis developed meningitis with a penicillin-resistant
      strain of Streptococcus pneumoniae while on prophylactic ampicillin. The
      microbiological aspects of management are discussed.

PMID- 8308321
TI  - Leptospirosis presenting as atypical pneumonia, respiratory failure and pyogenic
      meningitis.
AB  - A 20-year-old man who looked after a pack of hounds was admitted with a short
      history of headache, fever, haemoptysis and muscle cramps. Investigations showed
      type I respiratory failure with diffuse pneumonitis, pyogenic meningitis and
      raised liver enzymes. Leptospirosis was suspected and treated with the
      appropriate antibiotics leading to a full recovery. The diagnosis was confirmed
      by a titre of I/2560 to Leptospira icterohaemorrhagiae. The case illustrates an
      unusual presentation of this infection and argues for early antibiotic treatment.

PMID- 8308322
TI  - Recurrent lymphocytic meningitis associated with hereditary isolated IgG subclass
      3 deficiency.
AB  - We report the case of an otherwise healthy young adult woman who has suffered
      three episodes of lymphocytic meningitis of possible enteroviral aetiology during
      a 5 year period. Analysis of immunoglobulin subclasses has revealed a sustained
      reduction of IgG3 to below the fifth percentile. In addition, the patient's
      father and brother have a similar degree of IgG3 deficiency. Isolated IgG3
      deficiency has previously been described in association with recurrent upper
      respiratory tract infections, asthma, obstructive lung disease and enteral
      infections. However, our patient did not have any of these and there was no other
      identifiable immune defect to account for the recurrent meningitis. Although a
      mere chance association is possible, the case is interesting as antibody
      responses involving IgG3 tend to be triggered by protein antigens such as viral
      envelopes, while humoral immunity is known to be important in the clearance of
      enteroviral infection.

PMID- 8308323
TI  - Endocarditis caused by Kingella denitrificans.
AB  - We report the case of a 48-year-old man with native valve endocarditis caused by
      Kingella denitrificans. He was successfully treated with a combination of beta
      lactam antibiotics and aminoglycosides, after which he underwent valve
      replacement surgery. This case represents the first report in the literature of
      elective native valve replacement. Previously reported cases are discussed
      together with management options, including suggestions for the treatment of
      patients with beta-lactam allergy and those infected with beta-lactamase
      producing strains.

PMID- 8308324
TI  - Covert multi-focal infective arthritis.
AB  - Six patients with pre-existing rheumatic joint disease presented with
      overwhelming septicaemia but without overt signs of joint inflammation. Joint
      aspirates demonstrated multifocal staphylococcal infective arthritis. Despite
      intensive care all six died from the infection or its immediate sequelae. The
      contrast between this clinical entity and classical infective arthritis,
      presenting with one or more swollen, tender joints, is discussed.

PMID- 8308325
TI  - Chronic active toxoplasmosis in an immunocompetent patient.
AB  - We report the case of an apparently immunocompetent woman whose symptoms and
      signs have persisted for 8 years following a serologically and histologically
      confirmed diagnosis of toxoplasmosis. During this period she had two successful
      pregnancies despite persistently increased anti-toxoplasma IgM antibodies.
      Neither child is infected.

PMID- 8308326
TI  - Coxsackie B virus epidemiology and neonatal infection in Belgium.
AB  - Outbreaks of Coxsackie B virus infection occur mainly in the warm spring and
      summer when enteroviruses are most prevalent. A study of five Coxsackie B virus
      serotypes was made over the last decade by collecting and typing nearly all
      enteroviruses isolated in Belgium. The study showed that Coxsackie B virus
      infection appeared in waves. We describe two outbreaks of Coxsackie B virus
      infection in our maternity unit. The first took place in 1988, when Coxsackie B 2
      virus was the most prevalent serotype in the general population. One baby fell
      ill 6 days after birth and developed signs of meningitis. In a second baby the
      infection showed a diphasic pattern. The first phase was relatively mild but,
      after a period of recovery the child developed signs of myocarditis. After a
      period of low prevalence or complete absence from 1982 to 1988, Coxsackie B I
      virus reappeared in the summer of 1989. That summer, a small outbreak was seen in
      our maternity unit where one baby was infected from his mother and the infection
      spread from that baby to another one. Both babies developed meningitis but their
      convalescence was uncomplicated. A higher risk of outbreaks in nurseries was
      observed in summer when viruses are most prevalent. Measures to prevent such
      infections are discussed.

PMID- 8308327
TI  - Investigation of milk-borne Streptococcus zooepidemicus infection associated with
      glomerulonephritis in Australia.
AB  - An outbreak of infection due to Streptococcus zooepidermicus is reported. The
      index case was a patient who suffered an episode of septicaemia complicated by
      glomerulonephritis. Two other persons in his family were found to be asymptomatic
      throat carriers. The source of the outbreak was unpasteurised milk from a house
      cow on the farm where the family lived. Molecular studies confirmed that the
      strains isolated from the index case, the other family members and the cow's milk
      were identical. Although a renal biopsy was not performed, the diagnostic
      criteria for poststreptococcal glomerulonephritis were satisfied. The organism is
      an uncommon human pathogen that sometimes causes outbreaks of severe infection
      which may be associated with glomerulonephritis.

PMID- 8308328
TI  - Some early British contributions to tropical disease.

PMID- 8308329
TI  - Glycopeptide sensitivity of staphylococci.

PMID- 8308330
TI  - Not Branhamella catarrhalis: misidentification of oxidase-positive, Gram-negative
      cocci isolated from the genital tract.

PMID- 8308331
TI  - Impairment by verotoxin of tubular function contributes to the renal damage seen
      in haemolytic uraemic syndrome.

PMID- 8308332
TI  - Endocarditis following skin procedures.

PMID- 8308333
TI  - Atypical presentation of a patient with meningococcaemia.

PMID- 8308334
TI  - Serodiagnosis of giardiasis by counterimmunoelectrophoresis and indirect
      immunofluorescence tests.
AB  - Serodiagnosis of giardiasis by counterimmunoelectrophoresis assay (CIEP) and
      indirect immunofluorescence test (IFAT) were evaluated versus stool examination.
      Giardia lamblia antibodies were detected in sera of 46.9% and 53.1% using CIEP
      and IFAT respectively out of 49 giardiasis-infected children (5-10 years)
      diagnosed microscopically. Among the control group (22 children) 13.6% and 18.2%
      were positive by CIEP and IFAT respectively. The findings of the study showed
      that we can not rely on serology to diagnose giardiasis specially in cases with
      low excretion rates.

PMID- 8308335
TI  - Oral contraceptive pills in experimental schistosomiasis mansoni:
      parasitological, biochemical, histopathological and ultrastructural studies.
AB  - This study examines the effect of intake of oral contraceptive steroid in S.
      mansoni infected mice as regards parasitological, biochemical, histopathological
      and ultrastructural changes. Three groups were studied group I: S. mansoni
      infected mice received contraceptive pills six weeks post-infection (p.i.), group
      II: S. mansoni infected control and group III: non-infected control.
      Administration of oral contraceptive pills to S. mansoni infected mice results in
      significant reduction in tissue egg count with a high percentage of dead eggs as
      observed in the oogram study. There was statistically significant increase in all
      parameters of the hepatic functions except the prothrombin activity which showed
      significant decrease. Histopathological examination revealed less cellular
      granulomas with marked fibrosis, foci of hyperplastic changes in the liver cells
      and accentuation of cellular degenerative changes. On the subcellular level,
      there were marked proliferation and dilatation of rER and SER, evident increase
      of ribosomes, alteration in mitochondrial cristae with intra luminal inclusions
      and increase glycogen content of hepatocytes.

PMID- 8308336
TI  - Population dynamics and schistosomal infection of Biomphalaria alexandrina in
      four irrigation canals in Egypt.
AB  - The natural growth, reproductivity, mortality and schistosomal infection of
      Biomphalaria alexandrina, the snail vector of Schistosoma mansoni in Egypt, were
      studied for one year in four irrigation canals, namely El-Khassa and Radwan (Giza
      Governorate) and Sendebis and Sanafeer (Qalyoubiya Governorate). Radwan canal
      contains a considerably dense Biomphalaria population and three generations of
      snails (parents generation and autumn and spring generations) were recognized.
      Two phases of growth were distinguished in both autumn and spring generations, a
      faster phase followed by a slower one. The faster phase extends from January to
      May and from March to August in the autumn and spring generations, respectively.
      The daily mortality rate of snails was highest in the hot season (June-
      September) and lowest in the cold months (December--April). Continuous
      reproductivity of Biomphalaria snails was observed allover the year with highest
      values of reproduction index from November to March. Biomphalaria snails
      collected from El Khassa and Radwan canals were free of S. mansoni infection,
      while snails of Sanafeer canal carried patent infection in September and October.
      Prepatent infection was also found in Sanafeer canal in July and September and in
      Sendebis canal in September.

PMID- 8308337
TI  - Study of free living amoebae in Egypt.
AB  - At different locality in Egypt, free living amoebae (FLA) were detected in 32%,
      20% and 4% of water samples obtained from swimming pools, surface water canals
      and tap water respectively. Naegleria spp. were identified from 12 (75%) out of
      16 swimming pool samples and 6 (60%) out of 10 surface water & canals samples
      from different Governorates in Egypt, while Acanthamoeba spp. were identified
      from 4 (25%) of 16 swimming pools samples, 4 (40%) out of 10 surface water &
      canals samples and 2 (100%) tap samples. The isolated FLA in the present study
      were non-pathogenic as proved by the pathogenicity test.

PMID- 8308338
TI  - Studies on cutaneous leishmaniasis in El Hasana Center, North Sinai, Egypt.
AB  - The persistent of Cutaneous Leishmaniasis (CL) transmission mainly in Sinai and
      one or two foci in the Nile Valley and the outbreak of CL. in Nakhel Center form
      the rationale for including Leishmaniasis as one of the main health problems in
      Egypt. In this paper, it was aimed to spot-light survey humans for Cutaneous
      Leishmaniasis in El Hasana Center, North Sinai. Also rodents were trapped from
      several towns and villages within the Center to document the relative importance
      of the different species of rodents as animal reservoirs at the local or national
      level. The results showed 18 parasitologically proven human cses of CL. (14
      coming from the Nile Valley and 4 Bedouins). Eight species of rodents were
      trapped, natural infection was only demonstrated in two Meriones crassus in Ain
      El Gideirat and in one Gerbillus pyramidum in Abu Aweigila. The results were
      discussed on the light of the previous data obtained.

PMID- 8308339
TI  - Selective intestinal decontamination in patients with schistosomal hepatic
      fibrosis and low-protein ascites.
AB  - Selective intestinal decontamination (SID) for 7 days with norfloxacin (NF) was
      performed in 15 patients with schistosomal hepatic fibrosis (SHF) and low-protein
      ascites. Changes in ascitic fluid (AF) opsonic activity and complement3 (C3),
      complement4 (C4), total protein (TP) and albumin concentrations after NF therapy
      were compared with those of a control group composed of 15 untreated patients
      with similar characteristics. After oral NF administration, the mean % changes of
      AF opsonic activity & AF C3 & TP concentrations showed significant increases and
      were significantly higher than those in the control group. There were direct
      correlations between mean % changes in AF opsonic activity and C3 concentrations
      (r = 0.62). AF opsonic activity and TP concentrations (r = 0.54) and AF C3 and TP
      concentrations (r = 0.57) in the NF group. On the other hand, the AF C4 and
      albumin concentrations were not significantly changed in any group at the end of
      the study. Based on the results of the present study, it can be concluded that
      short-term NF therapy in patients with SHF and low-protein ascites increased AF
      opsonic activity and AF C3 and TP concentrations and hence, AF bactericidal
      activity. Study of larger numbers of patients for longer periods will determine
      if these beneficial effects on NF translate into a decreased incidence of
      spontaneous bacterial peritonitis in patients with chronic liver disease and high
      risk of infection.

PMID- 8308340
TI  - Immunofluorescent diagnosis of Chlamydia trachomatis infection of the respiratory
      tract and the eye.
AB  - Direct and indirect immunofluorescent antibodies as well as IgM antichlamydia
      antibodies were studied for diagnosis of 60 patients with Chlamydia trachomatis
      infection as well as 20 normal controls (group C). 30 Patients were suffering
      from C. trachomatis pneumonia (group A) and the other 30 patients were suffering
      from trachoma eye infection (group B). Indirect immunofluorescent technique (IIF)
      was positive 9.9% of group A. IgM antichlamydia antibodies by ELISA was positive
      in 23.3% and 16.6% in group "A" and "B" respectively. While highly positive
      results (60%) were obtained in conjunctival smears of group "B" when using direct
      immunofluorescent staining.

PMID- 8308341
TI  - Rodents and cutaneous leishmaniasis in Qasim, Saudi Arabia.
AB  - The past and the present studies in Saudi Arabia show that zoonotic cutaneous
      leishmaniasis (ZCL) is the most common and widely distributed form of
      leishmaniasis. The classic natural foci near human settlements exist in the
      Eastern Region and to less extend the Central Region. In the former region
      Psammomys obesus, Meriones crassus and M. libycus (?) are the animal reservoirs.
      In this paper, rodents were surveyed in Qasim (Central Region) to identify the
      reservoir host. The results showed that M. crassus is the reservoir host. Also,
      natural infection with Leishmania parasite was demonstrated in one M. libycus.
      The results were discussed on the light of the work done locally and regionally.

PMID- 8308342
TI  - Studies on the interrelation between rodents and their ectoparasitic acarines in
      Riyadh region, Saudi Arabia.
AB  - The ectoparasitic acarines of commensal and wild rodents collected from various
      areas in Riyadh Region were four species of mites (Laelaps nutalli, Ornythonyssus
      bacoti, Cheyletus eruditus and Articholaelaps glasgowi), and two species of
      ticks. (Immature stages) Rhipicephalus spp. and Hyalomma spp. In urban areas the
      highest infestation rate by mites was 49.9% on Rattus rattus followed by 18.5% on
      Rattus norvegicus. The highest rat-mite index was 2.3 on R. rattus followed by
      1.3 on R. norvegicus and 0.1 on Mus musculus. In semiarid areas, the highest rat
      mite index was 2.1 on Gerbillus spp. followed by 1.7 on Meriones spp., 1.6 on
      Jaculus jaculus and 0.9 on Acomys dimidiatus. The highest infestation rate by
      mites was on Meriones spp. followed by Gerbillus spp. and then A. dimidiatus.

PMID- 8308343
TI  - Detection of free-living amoeba (Acanthamoeba polyphagia) in the air conditioning
      systems.
AB  - Acanthamoeba polyphagia was found in the cooling towers of the air conditioning
      systems. This finding directs the attention to more studies on water and air
      conditioning systems of hospitals and dwellings and the relation to outbreaks of
      legionnaire's disease be caused by Legionella bacilli which complete its natural
      life cycle inside the Acanthamoeba.

PMID- 8308344
TI  - Treatment of human scabies by sulfur and permethrin.
AB  - Scabies is one of the most important prevalent contagious disease caused by itch
      mite "Sarcoptes scabiei." Many effective scabiecides have been suggested and
      tried. They differ in their side effects since they are applied on diseased skin
      sometimes all over the body. In this paper, sixteen parasitologically proved
      human scabies were successfully treated by 5% sulfur precipitate and 2.5%
      permethrin. Application of sulfur for one week or 2 applications of permethrin
      followed by a third one a week later proved to be safe and effective. The one
      week course of sulfur and the third application of permethrin acts against any
      emerging immature stages of the mite.

PMID- 8308345
TI  - Effect of temperature on the developmental stages of Wohlfahrtia nuba
      (Diptera:Sarcophagidae).
AB  - Total developmental time of flesh flies Wohlfahrtia nuba (Wiedemann) from first
      larval stage to adult emergence was 34.7, 23.5, 18.7, 13.4 and 13.6 days when
      reared at 21, 25, 29, 33 and 37 degrees C, respectively. There were no
      significant differences between both sexes (P > 0.05). The overall mean of the
      larval duration periods was shorter (P < 0.05) than pupal duration periods.
      Estimates of the lower developmental threshold temperatures (tL) were 12.8, 14.0
      and 13.6 degrees C and the thermal constant (K) were 116.8, 152.2 and 268.2
      degree-days for larvae, pupae and total developmental time, respectively. Pupal
      mortality was low at all temperatures used. The fly reached their maximum weight
      in pupal and adult stages at 21 degrees C. At all temperatures, the mean weight
      of pupa and adult was smaller (P < 0.001) in males than in females. The
      developmental rate, low mortality and greatest weight reached their optimal
      condition between 21 to 33 degrees C.

PMID- 8308346
TI  - Blind peritoneal biopsy with other diagnostic parameters in diagnosis of ascites.

PMID- 8308347
TI  - Mosquito age as a factor influencing the transmission of Wuchereria bancrofti.
AB  - Two mosquito species; Culex pipiens and Aedes caspius of different ages were
      experimentally infected with moderate microfilarial densities of Wuchereria
      bancrofti and examined for their vector potential to transmit this parasite.
      Tested age groups of Cx. pipiens supported the development of the infective stage
      of the parasite (L3) but those of Ae. caspius arrested its development especially
      aged mosquitoes. For Cx. pipiens, infection rates and the mean number of
      microfilaria (mf) were found decreased with insect age groups while their
      survival was not affected. Also, proportion of mosquitoes harbouring L3 of the
      parasite was quite similar for the examined age groups, however; the 4 days-old
      group was the highest. On the other hand, Ae. caspius capability to respond
      against W. bancrofti was decreased in older mosquitoes. The observed results may
      indicate certain influence of mosquito aging on the development of W. bancrofti
      which differ according to mosquito species.

PMID- 8308348
TI  - Studies on the ectoparasites (fleas and lice) on rodents in Riyadh and its
      surroundings, Saudi Arabia.
AB  - A survey was conducted on rodents from the Riyadh City and surroundings. Two
      species of fleas, Xenopsylla cheopis and Ctenocephalides felis felis together
      with Polyplax spinulosa were collected. The highest infestation rate by both
      fleas occurred on Rattus rattus followed by Rattus norvegicus and Mus musculus.
      Females of R. rattus and R. norvegicus were more infested by fleas than males. On
      the other hand, Meriones spp., Gerbillus spp., Jaculus jaculus and Acomys
      dimidiatus were infested with X. cheopis and C.f. felis. The highest infestation
      rate by fleas occurred on Gerbillus spp. followed by Meriones spp.

PMID- 8308349
TI  - Urino-genital myiasis due to Piophila casei.
AB  - Myiasis is a subject of medical and veterinary importance particularly, in
      tropical and subtropical regions. In this paper, three cases of human urino
      genital myiasis due to Piophila casei were identified and discussed.

PMID- 8308350
TI  - Effects of ration and Fasciola infection on some blood parameters of ewes.
AB  - This study was conducted using fourty cross-bred ewes in 5 groups of which one
      was kept as a control and the others were infected with metacercariae of Fasciola
      gigantica twice at the beginning of the experiment and 200 days from the first.
      The four infected groups fed on basal ration or high protein ration with or
      without mineral mixture. Blood samples were taken from the five groups to assess
      the concentrations of plasma fibrinogen and serum total proteins, albumin,
      globulin, calcium and inorganic phosphorous. Results indicated that ewes total
      serum protein, albumin and globulin were decreased by Fasciola infection. The
      decrease was only significant in ewes fed basal ration with or without mineral
      mixture. Mineral mixture had no effect on the later blood parameters of infected
      ewes although little improvement in blood serum globulin was noticed. Plasma
      fibrinogen decreased significantly by infection. The level of plasma fibrinogen
      was improved by feeding high protein ration but did not affect by adding mineral
      mixture to any of the ration used. Infection was also found to decrease blood
      serum inorganic phosphorous but not calcium level. Feeding high protein ration
      with or without mineral supplement maintained blood serum inorganic phosphorous
      as that of the uninfected ewes. Blood serum calcium to phosphorous ratio of ewes
      fed only basal ration was significantly higher than that of other groups.

PMID- 8308351
TI  - Toxoplasma gondii in Saudi blood donors a serological study using three tests.
AB  - A total of one hundred and fifty Saudi blood donors were examined for Toxoplasma
      gondii antibodies (IgG-IgM) by three serological techniques, 50 normal cross
      matched controls were subjected to the same examination. The number of positive
      donors for IgG by Indirect Haemagglutination test (IHA) was 36 (24%), by Enzyme
      Linked Immunosorbent Assay (ELISA) was 70 (46.7%), and by Immunofluorescent test
      (IFAT) 74 (49.3%). As to IgM the ELISA and IFAT showed 3 positive cases among the
      blood donors (2%). Rheumatoid factor and antinuclear antibodies were done for
      positive cases, and showed no significant cross reaction, IgG antibodies were
      significantly high in donors than in controls. The three tests were more or less
      dependable. However regarding simplicity, specificity, accuracy and time
      consumption factor IFAT was recommended for Toxoplasma IgG for all blood donors
      to avoid the risk of in infection.

PMID- 8308352
TI  - Effect of rice cultivation on the prevalence and infection rates of Schistosoma
      intermediate host.
AB  - In this study, it was aimed to explore the effect of rice cultivation on the
      prevalence, density and infection rates on the snail intermediate hosts of human
      schistosomiasis. A village was chosen and examine for the main water canal
      supplying the rice field by making three successive scoops at 10.20, 30, 40 and
      50 meters up stream the site of the pump supplying the rice field. The same was
      done in the large irrigation canal supplying 50 feddans of rice up to 100 meters
      (i.e. 10 sampling sites). Also the drains in between the rice fields were
      examined at 10 meters distance throughout the drain. The hunted snails were
      sorted, the Biomphalaria alexanderina and Bulinus truncatus were separated, their
      age was determined then crushed to look for immature stages under the microscope.
      Also the vegetations coming in the scoops were examined. The results showed that
      rice cultivation and irrigation is a suitable site for the prevalence and
      intensity of snails. Both species of snails were found in the main canal,
      irrigation canal and drains. All Bulinus truncatus snails were free from
      infections. The number of infected Biomphalaria alexanderina snails was
      significantly higher in the irrigation canal and drains than main canal which may
      be attributed to pollution of the drain water and irrigation canal by micturition
      and defecation or to the use of water in ablution.

PMID- 8308353
TI  - Factors affecting C3 in intestinal schistosomiasis.
AB  - Complement component C3 was investigated in sera of a group of schistosomal
      patients free from obvious nephritis. C3 was studied in relation to S. mansoni
      egg count, presence of HBsAg, and liver functions. C3 level was low in
      schistosomal patients than normal individuals. Levels were low in both HBsAg --ve
      and HBsAG +ve schistosomal patients. No significant difference was found between
      HBsAg --ve and HBsAg +ve in one hand, and between patients with egg counts more
      than 400 and those with egg counts less than 400 eggs/1 gr as regards level of C3
      on the other hand. Presence of ascites did not affect C3 concentration. Positive
      correlation was found with Serum albumin, but not with prothrombin concentration
      serum alkaline phosphatase or serum transaminases.

PMID- 8308354
TI  - Rodents and their arthropod ectoparasites in South Sinai Governorate, Egypt.
AB  - From the scientific point of research, little attention has been paid to South
      Sinai Governorate. In this paper, it was aimed to study the rodent population and
      their arthropod ectoparasites in three selected areas; St. Catherine, Wadi Sahab
      and Wadi Feran. The highest rodent trap index was in St. Catherine, followed by
      Wadi Sahab and then Wadi Feran. Mus musculus was predominant mainly indoors in
      the three areas while Acomys C. dimidiatus was predominant mainly outdoors.
      Dipodillus dasyurus was found in St. Catherine and Wadi Sahab, Eliomys quercinus
      in St. Catherine and Wadi Feran and Meriones sacramenti in Wadi Feran. The
      commonest arthropod ectoparasites in a descending order were Xenopsylla cheopis,
      X. ramesis, Ctenocephalides canis, Rhipicephalus sp., Hyalomma sp., Ornithonyssus
      bacoti (on M. musculus), Haemogamasus pontiger, Hirstionyssus isabellinus (on
      A.c. dimidiatus and Meriones sacramenti). The medical and veterinary importance
      of the results were discussed.

PMID- 8308355
TI  - Susceptibility of three tick Hyalomma spp. from North Sinai Governorate to
      certain pesticide groups.
AB  - Three species of Hyalomma tick, (H. anatolicum, H. dromedarii and H. impeltatum)
      were collected from camels in North Sinai. The susceptibility of adult females
      and males of each species to four different groups of insecticides (BHC,
      Fenitrothion, Permethrin and Baygon) were determined. The results of Lc50 values
      showed that BHC was the most effective compound against adult males and females
      of H. impeltatum, whereas the superior efficiency against H. anatolicum and H.
      dromedarii occurred by Baygon and Permethrin respectively on both males and
      females. Also the results indicated that the adult males of all tested species of
      ticks were more susceptible to all the tested insecticides than the adult
      females.

PMID- 8308356
TI  - Epidemiological studies on human scabies in Cairo.
AB  - Nowadays, human scabies is more or less a public health problem in Egypt,
      particularly among school children. The results of this epidemiological studies
      among one hundred scabietic patients showed that (a) Scabies is widespread among
      children and youth particularly students (b) The sex and the site distribution
      are attributed to the risk factor of exposure to infestation (c) Scabies is a
      disease determined by Sociodemographic and Hygienic customs of the population
      with high familial incidence among the patients. The whole results were discussed
      on the light of the work done in Egypt and similar countries.

PMID- 8308357
TI  - Parasitological and clinical studies on human scabies in Cairo.
AB  - This study is a parasitological and clinical study on human scabies. This study
      was carried out on 100 patients attending the Dermatology Outpatient Clinic at
      Ain Shams University Hospitals, including 54 males and 46 females. All patients
      were subjected to detailed history taking, complete dermatological examination
      including Skin Scraping Test and Burrow Ink Test. Younger patients attended the
      dermatology clinic earlier than older patients, who usually delayed their visits
      until complications occurred. Scratching, erythematous papules and secondary
      infected lesions were the commonest lesions. The hands, wrist and external
      genitalia were the most frequently affected sites while the feet, ankles, knees
      and back were the least affected. Burrows could only be detected in 40% of
      patients. The most frequent sites were the web spaces, external genitalia, and
      finger sides. Burrow Ink Test was positive among 85% of patients with burrows
      while mites could be identified by Skin Scraping Test in 55% of patients. The
      most frequent clinical manifestations in the parasitologically positive patients
      were itching, burrows, and papules, and the most frequent sites were the web
      spaces, and the finger sides. Multiple sites affection was the characteristic
      feature among the preschool age children who represented 14% of cases.

PMID- 8308358
TI  - Parasitic infections among patients of Al Nour Specialized Hospital.
AB  - Parasitic infections are still the main public health problem in the developing
      countries. Saudi Arabia is a developing country beside, it is the main center for
      all muslims for "Haj and Omra". Most of the work done in the field of parasitic
      infections dealt with Saudis or Yemenis. In this paper, most of the patients are
      muslims coming for Haj and or Omra. The highest rate if infection was 11.63% for
      Giardia and the lowest was 0.007% for Fasciola. Urine examination showed S.
      haematobium (2.99%), T. vaginalis (3.82%) and Enterobius eggs (0.04%). Malaria
      infection was also encountered. P. vivax showed 2.5% and P. falciparum showed
      6.5% among a total of 5233 suspected cases. Still the direct examination of urine
      and stool being the most reliable method for diagnosis of helminthic infections.
      The whole results were discussed.

PMID- 8308359
TI  - Studies on larval digenetic trematodes of xiphidiocercariae from some Egyptian
      fresh water snails.
AB  - Six xiphidiocercariae are described from seven Egyptian snails, includes
      Cleopatra bulimoides, Malanoides tuberculata, Lymnaea cailliaudi, Bulinus
      truncatus, Biomphlaria alexandrina and Lanistes carinatus collected from Giza
      (Abou Rawash) and Qualiobyia (Qualiuob). Details are presented on the morphology,
      behavior of the cercariae, as well as other larval stages within the snails, with
      discussion and comparison between the previously described cercariae.

PMID- 8308360
TI  - Studies on the nematode parasites from Egyptian rodents. I. Spirurid nematodes.
AB  - Three spirurid nematode species have been collected from Egyptian rodents in Giza
      province. Streptopharagus kuntzi was collected from stomach and small intestine
      of Rattus ratus, R. norvegicus, Arvicanthis niloticus and Gerbillus gerbillus.
      Protospirura muris and P. marsupialis have also been collected from A. niloticus,
      R. rattus and R. norvegicus but P. marsupialis was collected only from the
      stomach while P. muris collected from stomach and small intestine. P. marsupialis
      was firstly recorded in Egypt during this work and no males of this species were
      collected. Females of S. kuntzi and P. muris showed marked dominance over males.
      Streptopharagus sudanensis and S. kuntzi are placed in synonomy.

PMID- 8308361
TI  - Seroprevalence of Toxoplasma and cytomegalovirus in complicated pregnancies.
AB  - Anti-Toxoplasma and anti-cytomegalovirus (CMV) antibodies were sought in 200
      pregnant women (100 with complicated pregnancies and 100 matched controls without
      any hazards) by ELISA test. Sixty-five per cent of the women with complicated
      pregnancies had Toxoplasma antibodies, while 51% had CMV antibodies. Toxoplasma
      seroprevalence alone was higher in women with intrauterine foetal death (IUFD)
      (80%). CMV seroprevalence alone was higher in women with premature labour (44.4%)
      and women with stillbirth (40%). Seroprevalence of both Toxoplasma and CMV was
      clearly higher in women with abortion (55.7%). Seroprevalence of Toxoplasma and
      CMV in the control group was 6% and 30%, respectively. These data confirm that
      Toxoplasma and CMV are important causes of complicated pregnancy.

PMID- 8308362
TI  - Isoenzyme characterization of Leishmania isolates from patients in El Nour
      Specialized Hospital, Saudi Arabia.
AB  - No doubt, the three forms of leishmaniasis (VL, ZCL & ACL) are well documented in
      Saudi Arabia. The basis of epidemiological studies must be adequate
      identification of the Leishmania patients. Seven leishmanial strains have been
      isolated from patients attending El Nour Specialized Hospital, Makka Al
      Mokarrama. The majority of the patients of this hospital are temporary visitors
      to Makka Al Mokarrama for "Haj and Omra". Isoenzyme characterization by cellulose
      acetate electrophores's used nine enzymes was done. The seven isolates were: two
      L. donovani zymodeme LON 41 (Indian patient) and LON 46 (Sudanese patient); three
      L. tropica zymodeme LON 71 (2 Yemeri patients) and LON 22 (Egyptian patient) and
      two L. major zymodeme LON 4 (2 Saudi patients).

PMID- 8308363
TI  - The effect of praziquantel treatment on the liver functions, worm burden, and
      granuloma size using two drug regimen in murine Schistosoma mansoni infection.
AB  - The effect of single dose of praziquantel (400 mg/kg) or two doses on two
      consecutive days was studied in mice infected with S. mansoni. With the single
      dose there was improvement in the serum protein pattern towards pre-infection
      values & a transient rise in serum transaminases which soon declined to normal.
      Improvement was more evident after using two doses of praziquantel (P < 0.001).
      Worms were eradicated by 70%. 77% and 80% after the single dose and by 88%, 92%
      and 95% after two doses. Granuloma size was reduced by 50%, 54% and 60% after
      single dose and by 58% and 73% respectively after 10, 20, and 30 days from
      treatment.

PMID- 8308364
TI  - [The indications and limitations of open heart surgery without homologous blood
      transfusion in children and infants].
AB  - Open heart surgery without homologous blood transfusion in adults is a
      generalized method, but not in children and infants. We have attempted to perform
      open heart surgery without blood transfusion in small children and infants, and
      report here our experiences and ideas in this regard. The number of open heart
      surgeries we performed on patients less than 15 years old was 117 from April 1988
      to April 1993. In 57 patients among them we attempted open heart surgery with
      bloodless priming in the cardiopulmonary bypass circuit. Eleven patients were
      given blood transfusion during the operation or the post-operative period.
      Another 46 discharged without blood transfusion. From April 1988 to December 1990
      (the earlier period) we used the conventional style cardio-pulmonary bypass
      circuit with gravity venous drainage for 12 patients undergoing open heart
      surgery without blood transfusion. The lowest weight of these patients was 13 kg
      and the main diseases were ASD and mild VSD. From January 1991 to April 1993 (the
      later period), we used the new type cardio-pulmonary bypass circuit with lower
      priming volume for 34 patients undergoing open heart surgery without blood
      transfusion. The youngest age was 7 months and the lowest weight was 6.5 kg. The
      diseases were ASD (9), mild VSD and VSD/PH (15), TOF (6) and other (4). In the
      new cardiopulmonary bypass system, the venous reservoir and cardiotomy sucker are
      given negative pressure ((-10)-(-40) mmHg) with a vacuum not a pump, and only one
      roller pump is used for the arterial pump.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308365
TI  - [A case of Salmonella osteomyelitis of the rib].
AB  - Salmonella osteomyelitis is a rare disease occurring at a frequency of less than
      1% of all cases of osteomyelitis, we report a case of salmonella osteomyelitis of
      the rib, which was hard to differentiate from chest wall tumor. A 40-year-old man
      without gastrointestinal symptoms was admitted to our hospital for swelling of
      the right mammary region. It was suggestive of inflammatory pseudotumor because
      the swelling diminished, and we could not establish a diagnosis of abscess by
      scintigraphy with gallium-67 or by computed tomogram (CT). Drainage was carried
      out in the chest and about 10 ml of pus was removed. A culture was taken from the
      pus, revealing salmonella enteritidis, he was treated by local wound care and
      ABPC (aminobenzyl-penicillin). The open wound became sterile in 40 days, and was
      closed 46 days after being opened for drainage.

PMID- 8308366
TI  - [A case of gastric cancer occurred after coronary artery bypass grafting using
      the right gastroepiploic artery].
AB  - We experienced a rare case of the gastric cancer occurred after the coronary
      artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA). On
      April, 1990, a 74-year-old woman underwent CABG using RGEA for angina pectoris
      due to 99% stenosis of the right coronary artery. Anorexia and vomiting appeared
      from December 1992. Examination of the stomach by an oral procedure led to a
      diagnosis of the pyloric stenosis due to the gastric cancer. The coronary
      arterial lesion was progressive, and 90% stenosis of LAD (#6, #7) was noted. On
      February 1993, the re-CABG and the gastrectomy were performed simultaneously. The
      re-CABG using the saphenous vein was performed to #3, and additional CABG using
      the bilateral internal thoracic artery were performed to #8 and #9. At the same
      time, the gastrectomy were performed and RGEA was resected to remove the R2 lymph
      node completely. If the root of RGEA had been exposed completely at the first
      operation, RGEA could be preserved as the bypass graft.

PMID- 8308367
TI  - [A case of multiple primary malignant melanoma of the esophagus].
AB  - A case of multiple primary malignant melanoma of the esophagus was reported. A 66
      year-old male was referred to the hospital with complaints of appetite loss and
      dysphagia. A barium swallow revealed two polypoidal tumors of approximate equal
      size, one in the lower third of esophagus and the other in the cardiac region of
      stomach. The tumors were shown blackish at endoscopy and biopsy yielded a
      histological diagnosis of malignant melanoma. Abdominal CT, abdominal
      ultrasonography and hepatic arteriography showed metastasis to liver and rt
      paracardiac lymph nodes. However, no primary lesion of malignant melanoma but
      esophagus was found through the preoperative clinical examination. Partial
      resection of the esophagus along with the proximal of stomach and the paracardiac
      lymph nodes was performed. Microscopically, the typical finding of junctional
      activity adjacent to the tumor mass was not obtained but we diagnosed as primary
      esophageal tumor because melanocytes were present along the basal layer of normal
      esophageal mucosa and groups of melanophages were found in the submucosal layer.
      However, we could not conclude which polypoidal tumor was the primary lesion. The
      patient received systemic chemotherapy postoperatively and is alive 5 months
      after surgery.

PMID- 8308368
TI  - [Ehlers-Danlos syndrome with impending ruptured thoracic descending aortic
      aneurysm in a young adult--a case report].
AB  - We here report on a rare case of Ehlers-Danlos syndrome type IV with impending
      ruptured thoracic aortic aneurysm in a young adult. A 38-year-old man complained
      of severe back pain and transient paralysis in both legs. He was diagnosed as
      having an impending ruptured thoracic descending aortic aneurysm. Emergency
      operation which was aneurysmectomy and reconstruction of the descending aorta was
      performed. The fact that the aneurysm (11 cm) in a patient was so large for his
      age and the abnormal subcutaneous fatty tissue suggested the existence of
      systemic metabolic disease. An analysis of collagen extracted from the patient
      revealed the absence of type III collagen. Furthermore, an electron microscopic
      analysis finding that the collagen fibrils was of non-uniform size lead to the
      diagnosis of Ehlers-Danlos syndrome, Type IV (arterial type). Postoperatively the
      patient suffered paralysis in both legs due to ischemia of the spinal cord.
      However, his general condition was stable. He was transferred to another hospital
      for rehabilitation of both legs 60 days after the operation. Although the
      physical signs usually associated with Ehlers-Danlos syndrome were absent in this
      case, diagnosis followed electrophoresis of collagen extracted from the patient.
      As a result of the above observation, we recommended analysis of collagen in
      cases where the size of the aneurysm or the age of the patient appear unusual
      even though physical signs of Ehlers-Danlos syndrome are absent.

PMID- 8308369
TI  - [Application of PCPS (percutaneous cardiopulmonary support) to the resuscitation
      of DOA (dead on arrival) patients].
AB  - We report three cases of DOA patients who were resuscitated by using PCPS. All
      had resisted standard advanced life support methods. The conditions responsible
      for the heart arrest were acute myocardial infarction (AM1) in 2 (case 1 and 3)
      and subarachnoid hemorrhage (SAH) in the other (case 2). All 3 were resuscitated
      by PCPS. Case 1 survived with a slight neurological deficit. Case 2 succumbed to
      SAH 3 days later. Case 3 was transferred to left heart bypass but succumbed to
      hemorrhagic infarction of the brain 6 days later. Although this system allows
      rapid and simple deployment and provides a benefit in resuscitation of DOA
      patients in a state that is refractory to standard cardiopulmonary resuscitation,
      the problem of indication for resuscitation remains to be solved.

PMID- 8308370
TI  - [A case report of successful open valvotomy in neonate with critical aortic
      stenosis].
AB  - Open valvotomy was successfully performed in neonate with critical aortic
      stenosis using cardiopulmonary bypass. The baby was referred to our hospital at
      the age of 24 days with very grave state, and needed intensive care including
      endotracheal intubation and inotropic support. Critical valvular aortic stenosis
      was confirmed by echocardiography. Poststenotic dilatation and enough size of
      short axis LV dimension were reported, and aortic annulus was measured 6 mm in
      diameter. Without catheterization and angiography, open valvotomy was performed
      with moderate hypothermia and ischemic arrest using single dose of cold
      cardioplegia at the age of 29 days. Bicuspid aortic valve was thick and
      dysplastic with thick gelatinous cusp edge, however commissurotomy was applicable
      in two direction. The diameter of aortic opening was enlarged from 2 mm to 7 mm.
      Total bypass and aortic cross clamp time were 78 and 28 minutes respectively. The
      baby recovered uneventfully and there was no evidence of significant AS or aortic
      regurgitation in echocardiography 7 months after surgery. Sorts of reoperation
      for restenosis or regurgitation were reported. The results of reoperation for
      regurgitation were reported to be poor, especially in young infants who should be
      performed aortic valve replacement. However, residual AS could be manipulated
      with re-valvotomy, PVB, apico-aortic conduit or AVR. As the choice of first
      relief of critical AS without other anatomical disadvantages including
      hypoplastic left ventricle, endocardial fibroelastosis, and mitral stenosis, it
      would be crucial for late results to prevent progression of aortic
      regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308371
TI  - [Description of arterial grafts from the aspect of preoperative angiography].
AB  - Bilateral internal thoracic arteries (ITA) and right gastroepiploic artery (RGEA)
      have come into more frequent use of late in coronary revascularization.
      Angiography of these arterial grafts, however, is performed only postoperatively
      in almost all patients. There have, so far, been no reports giving a preoperative
      angiographic description of each arterial graft. In this paper, we describe a
      study in which we performed preoperative angiography of ITA and RGEA and made a
      comparison of various grafts, which yielded interesting findings. Twenty-four
      patients (68 arterial grafts) who were judged to need surgery were performed
      preoperative angiography of the grafts. The diameter of ITA was measured at three
      points--the proximal part (Prox), center (Cent) and bifurcation of the artery
      near the rectus abdominal muscle (Bif). The diameter of RGEA was measured at two
      points--the proximal part and at 1/2 of the greater curvature of the stomach
      (Mid). The graft diameter of RGEA was 2.78 mm and significantly the largest,
      followed by RITA (2.59 mm) and LITA (2.08 mm), when the diameters of the proximal
      parts of the grafts were compared. Comparison of the diameters of RGEA-Mid and
      ITA-Bif, which were expected to be the anastomosis sites, also showed that RGEA
      was significantly the largest, and that the right ITA tended to be larger than
      the left ITA. Of the 24 patients, 68 arterial grafts, on which angiography was
      performed, 2 patients were found to have arterial occlusion and 1 to have
      arteriostenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308372
TI  - [Experience in surgical management for active aortic valve endocarditis with
      periannular abscess--outcome of abscess cavity after patch closure].
AB  - Two patients with active aortic valve endocarditis and periannular abscess
      underwent surgical management. Both patients had bicuspid aortic valves.
      Involvement of the aortic annulus with the formation of the periannular abscess
      was found at one third circumference in the aortic annulus and extended to the
      sinuses of Valsalva. In one patient the periannular abscess ranged from the right
      side of the ostia of a left coronary artery to the right commissural region, and
      in another patient it existed at the left commissural region. the ostia of
      coronary arteries were separated from the inflammatory and necrotic tissue in
      both patients. The wall of periannular abscess could not be totally excised.
      Instead, debridement and transaortic patch closure of the abscess cavity were
      performed. In the former patient, partial resection of the aneurysmal wall of the
      abscess was performed and the remaining aortic wall was approximated with extra
      luminal sutures supported by Teflon felt pledgets. However, in the latter
      patient, the plication of the abscess wall could not be performed. Prosthetic
      mechanical valve was implanted at the paraannular position by utilizing the
      patch. In the former patient it took a month and a half until the disappearance
      of the inflammatory reaction, and the echo free space could not be detected at
      the same place of the abscess cavity by the two-dimensional echocardiogram since
      early postoperative period. However, in the latter patient it took three months
      until the disappearance, and the echo free space had been existing at the same
      place for thirteen months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308373
TI  - [The youngest case of isolated interruption of the aortic arch without associated
      cardiac anomalies].
AB  - A five-month-old girl was admitted to our institute because of the systolic blood
      pressure gradient of 42 mmHg between upper and lower extremities. Cineangiography
      revealed that the brachiocephalic artery originated from ascending aorta, while
      the left subclavian and left vertebral arteries took their origin from the
      descending aorta. However, the left common carotid artery was not visualized
      either on the angiogram or on the digital subtraction angiogram. No other
      associated cardiovascular anomalies, such as patent ductus or ventricular septal
      defect, were found. Therefore the diagnosis of isolated interruption of the
      aortic arch (IAA) Celoria-Patton type C, was made. As the heart failure gradually
      progressed, the aortic arch reconstruction with a extended
      polytetrafluoroethylene graft of 10 mm in diameter under extracorporeal
      circulation utilizing separate ascending aortic cannulation were performed. Her
      postoperative course was uneventful. The majority of cases with IAA associated
      with cardiac anomalies require surgical intervention in the neonatal period or in
      infancy. However, clinical course of isolated IAA generally resembles to that of
      the post ductal coarctation of the aorta, and most of the isolated interruption
      is diagnosed in adulthood. The infant is the youngest case with isolated IAA
      undergone aortic arch reconstruction with success ever reported in the
      literature.

PMID- 8308374
TI  - [A case of partial anomalous pulmonary venous return to inferior vena cava and
      left atrium (Scimitar syndrome)].
AB  - Scimitar syndrome is relatively uncommon syndrome. A 14-year-old female referred
      to our hospital for abnormal shadow of chest fluoroscopic examination. She had no
      symptom except cough due to bronchial asthma. Chest X-ray film showed Scimitar
      sign. Cardiac catheterization revealed 30% left to right shunt without atrial
      septal defect. Pulmonary angiography showed anomalous pulmonary vein was drained
      to inferior vena cava and left atrium. Surgical correction was attempted
      monitoring the pulmonary arterial pressure. Anomalous pulmonary vein and systemic
      arteries were ligated and divided at the level of diaphragm. Postoperative course
      was smooth. We have found 4 similar operated cases previously reported in the
      world.

PMID- 8308375
TI  - [Aneurysm of the diverticulum of the ductus arteriosus].
AB  - Aneurysm of the diverticulum of the ductus arteriosus in adult is rare, with only
      37 cases reported so far in the literatures. A 18-year-old male was admitted for
      abnormal tumor shadow in the scout chest X-ray film. Ductal aneurysm was
      preoperatively diagnosed by chest CT scan, MRI, UCG, and angiography, and was
      confirmed by the intraoperative findings. In this patient, narrow isthmus and
      ductus diverticulum were supposed to be contributing factors for aneurysm
      formation. The aneurysm was approached through a posterolateral thoracotomy and
      aneurysmal orifice was closed with a trimmed dacron graft under partial femoro
      femoral cardiopulmonary bypass. Postoperative course was uneventful.

PMID- 8308376
TI  - [A successful case of valve-sparing surgery for tricuspid valve endocarditis].
AB  - A successful repair for infective endocarditis of the tricuspid valve is
      presented. A 35-year-old man was referred to our hospital complaining of high
      fever despite antibiotic chemotherapy. Lung scan showed multiple thromboembolism.
      Blood cultures revealed staphylococcus aureus. Echocardiography showed
      vegetations attached to the tricuspid valve and severe tricuspid regurgitation.
      Conservative surgery such as vegetectomy and DeVega's annuloplasty was
      successfully carried out. The patient's postoperative course was uneventful. The
      conservative surgery might provide a satisfactory result in the selected cases
      with localized vegetation and minimum valve involvement.

PMID- 8308377
TI  - [Removal of infected total pacemaker system under extracorporeal circulation--a
      case report and review of the Japanese literature].
AB  - A 35-year-old male with sick sinus syndrome was complicated with recurrent local
      infection at the site of the generator pocket associate with a retained pacemaker
      lead, followed by septicemia presenting with Staphylococcus aureus. Several
      attempts to remove the lead via the implantation vein by direct traction were
      performed unsuccessfully because the leads were strongly adhered to the trabecula
      of the right ventricle. Repeated debridement employing antibiotic therapy was
      ineffective. As a last resort, we finally operated under extracorporeal
      circulation (ECC) 24 months after the first implantation and 22 months after
      initiation of the local infectious episode. As we found it difficult to remove
      the leads by traction even under direct vision, we used the vinyl chloride tube,
      which is a part of the ECC circuit, as a sheath for applying countertraction
      around the lead tip to prevent the myocardial wall from being torn and extracted
      together with the lead tip. The lead was removed successfully and a new
      epicardial lead was implanted. The postoperative course uneventful and no
      recurrence has occurred after 1 year. In reviewing the Japanese literature, 10
      case, operated on under ECC to remove the infected retained leads, were described
      in detail. Among them, eight cases had undergone previous debridement including
      removal of the generator and the subcutaneous portion of the lead. It is clear
      that removal of all of the pacemaker system is necessary for eradication of
      infection. Adhesion of the lead to the wall is firm. Only one case besides ours
      succeeded in having its lead removed without requiring incision of the tissue
      around the lead tip.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308378
TI  - [Planned combination therapy of coronary artery bypass and PTCA in ischemic heart
      disease].
AB  - Concomitant planned therapy consisting of a coronary artery bypass operation and
      percutaneous transluminal coronary angioplasty (PTCA) was attempted to shorten
      the period of cardiac arrest and make operations safer in patients undergoing
      emergency coronary artery bypass operations or coronary artery bypass operations
      in cases of significantly reduced left ventricle function or small perfusion
      lesions. The bypass operation was performed to treat only the main lesion and
      PTCA was undertaken 1-2 months later for coronary revascularization to treat
      secondary lesions. Finally, complete coronary revascularization was achieved.
      This concomitant method was performed on three cases. In all of these cases, two
      grafts were made and 1-2 lesions were dilated by PTCA. It was suggested that
      planned concomitant coronary artery bypass operations and PTCA provide a safer
      method of treatment in certain selected cases.

PMID- 8308379
TI  - [Coronary artery bypass grafting to total occlusion of all three coronary
      vessels].
AB  - We studied total occlusion of all three coronary arteries. From 1975 to 1992, a
      total of 4,100 patients underwent coronary arteriography at Show University
      Hospital. Of these, four patients (0.1%) had complete occlusion of all three
      coronary arteries and all of them underwent coronary artery bypass grafting
      (CABG). The mean numbers of coronary risk factors were only 2.3 but history of
      angina of effort were long-standing such as 4 to 29 years (mean 16.3 yr). All
      cases had previous episodes of myocardial infarction. Three cases (75%) had
      aortic aneurysm. One case was also diagnosed as Leriche syndrome besides
      coexisting aneurysm. Coronary arteriogram showed total occlusion of right
      coronary artery, left anterior descending artery and left circumflex artery in
      the segment of 1.6 or 7 and 11 respectively. All cases had intracoronary
      anastomosis and intercoronary anastomosis. Among 12 occluded coronary arteries of
      all four cases, 11 were distally visualized with contrast medium via collateral
      flow but good opacification of the distal coronary trees were not seen. Also
      proper assessments of cardiac performance including viability of myocardium were
      not established because all cases were in the state of C.C.S grades IV. But
      significant clinical recovery were obtained in all cases after CAGB of three or
      four bypass. We conclude that these results might be a useful suggestion for the
      treatment of total occlusion of all three coronary arteries.

PMID- 8308380
TI  - [Is it safe and available to transfuse directly the shed mediastinal blood after
      cardiac surgery?].
AB  - Autotransfusion of the shed mediastinal blood after cardiac operations was
      performed in 20 cases (ATS group). Safety and efficacy of the autotransfusion
      were studied comparing with the 10 cases without autotransfusion (control group).
      A 65.1 +/- 17.1% of bleeding volume within 24 hours after surgery was
      autotransfused in the ATS group. The ATS group received 1,396 +/- 1,674 ml of the
      banked blood compared with 780 +/- 1,194 ml for the control group. There was no
      significant difference between two groups in regard to saving the banked blood.
      Hematological and biochemical studies after surgery in the ATS and control groups
      revealed that CPK, BUN and creatinine of the ATS group were significantly higher
      than those of the control group, although these changes were transitory and
      trivial. However, prothrombin time of the ATS group was lower than that of
      control group, so there may be the possibility that this technique itself
      increases the hemorrhage. Since the cardiotomy filter was obstructed with clots
      in cases of massive bleeding, shed mediastinal blood may not be fully
      defibrinogenated in the cases with massive bleeding. These results lead to the
      following conclusions: autotransfusion of the shed mediastinal blood after
      cardiac operations is a safe method, but the efficacy of it is doubtful.

PMID- 8308381
TI  - [Clinical reassessment of open mitral commissurotomy as a treatment for mitral
      valve stenosis: a comparative study with percutaneous transvenous mitral
      commissurotomy].
AB  - Recently, percutaneous transvenous mitral commissurotomy (PTMC) was applied as a
      treatment for mitral valve stenosis (MS) and patients who received PTMC are
      increasing. The objective of this study is to establish therapeutic strategy for
      MS by comparing the indication and clinical results of open mitral commissurotomy
      (OMC: n = 95) and PTMC (n = 54). Both groups showed almost equivalent
      preoperative data in echocardiographic score and cardiac catheterization, and
      postoperatively, they obtained almost same results. But when the author defined
      that successful commissurotomy is to gain the following postoperative cardiac
      catheterization data: mitral valve gradient < 10 mmHg, mitral valve area (MVA) >
      or = 1.3 cm2, mitral regurgitation < or = Sellers II/IV, success rate was higher
      in OMC group up (72%) than PTMC group (63%). There was no difference between OMC
      group and PTMC group in the early mortality and late survival. But reoperation
      free rate at the four postoperative year was higher in OMC group (100%) than PTMC
      group (94.5%). We found that the factors of unsuccessful PTMC were 1) MVA < 0.8
      cm2, 2) total echo score > or = 8 and 3) subvalvar thickening score > or = 3 in
      the preoperative data. We conclude that PTMC can be applied for MS with mild
      subvalvar lesion (subvalvar thickening score < or = 2) and OMC is superior to
      PTMC for releasing subvalvar stenosis than PTMC. However, mitral valve
      replacement might be a procedure of choice for MS with severe subvalvar lesion
      (subvalvar thickening score 4).

PMID- 8308382
TI  - [Experimental study of effect on lung in pig supported with RVAD].
AB  - Ventricular assist device (VAD) has a potent assist effect in the treatment of
      severe cases of acute heart failure, exhibiting excellent results at present.
      Right ventricular assist device (RVAD) has a potent flow volume assist effect in
      severe right heart failure, but in possibly induces aggravation because of
      pulmonary function disturbance, left heart failure, etc, since it supplies blood
      to the low-pressure pulmonary circulation system. However, its assist effects and
      drawbacks have not yet been examined sufficiently. These points, an acute
      experiment was performed on the effect of RVAD-induced changes in assist flow
      volume on hemodynamic changes and the lungs. Pulmonary arterial trunk of pigs
      weighting 40 +/- 3.4 kg were strangulated to obtain right heart failure models of
      pulmonary arterial blood flow reduced to about 60%. RVAD was then set to run on
      the models at a fixed rate (100 beats/min, S/D 35%). The models with RVAD flow
      about 30% of Ao flow were defined as Group I (low flow assist group: N = 9) and
      those with RVAD flow about 60% of Ao flow were defined as Group II (high flow
      assist group: N = 9), and results were compared between both groups. RVAD showed
      remarkable right ventricular preload relieving effect in both groups. The left
      cardiac function in Group II after 3 hours of RVAD run differed significantly
      from Group I in LVRDF, LAP, AoP, and Ao flow, and tended to aggravate them when
      the left cardiac function was reduced. Pulmonary function changes in Group II in
      terms of PaO2, PaCO2, SaO2, and A-aDO2 change rates suggested retention to some
      extent of gas exchange capacity and gradual decrease in gas diffusion capacity.
      In Group II after 3 hours of RVAD run, pulmonary extravascular thermal volume
      increased significantly, ACE levels decreased significantly, and the lungs
      presented morphologically high-level edematous changes, suggesting the possible
      damage to the lung physiological function in Group II. It was considered that
      excess flow volume assist during right ventricular assist alone may possibly
      induce left heart failure and that the assist volume should be decided carefully
      with attention paid to the left ventricular and pulmonary function.

PMID- 8308383
TI  - [Relationship between deep body temperature and hemodynamics in pediatric
      patients with congenital heart disease].
AB  - Relationship of the abdomen-sole deep body temperature difference (DBT) to the
      hemodynamics was examined in patients with congenital heart disease. Hemodynamic
      data were obtained by routine cardiac catheter examination, and DBT was measured
      during the catheterization. Significant positive correlation was found between
      DBT and systemic-pulmonary flow ratio (Qp/Qs) (r = 0.85, p = 0.001). DBT was
      maintained below 2 C degrees in almost every patient when the Qp/Qs was less than
      2, whereas DBT rose rapidly when the Qp/Qs was more than 2. Furthermore, systemic
      blood flow and arterial-venous oxygen difference ranged widely within the normal
      values when DBT was less than 2 C degrees. On the other hand, when DBT was more
      than 2 C degrees, systemic blood flow and arterial-venous oxygen difference
      tended to show fixed values which were around the normal upper or lower limits.
      This means that systemic circulation is marginally adapted when the Qp/Qs is more
      than 2. The measurement of deep body temperature difference is noninvasive, easy
      and useful as a circulatory monitor in pediatric patients with congenital heart
      disease.

PMID- 8308384
TI  - [Rescue effect of 15-deoxyspergualin for acute rejection on heart transplantation
      -using a rat model].
AB  - 15-Deoxyspergualin (DSG) attracts a lot of attention as an immunosuppressive drug
      which has less side effects these days. In the present study, we researched the
      rescue effect of DSG for acute rejection on heart transplantation (HTX) by using
      rat models. We performed 40 heterotopic heart transplantation models. We injected
      them DSG (group A: 5 mg/kg/day, group B: 10 mg/kg/day) intravenously through 3
      days, starting from the 3rd day the 4th day, and the 5th day after HTX. Our
      previous study showed the pathology on the 3rd day after HTX corresponded to mild
      rejection, the 4th day to moderate rejection, and the 5th day to severe
      rejection. One day after the injection was completed, the recipients were
      sacrificed. The rescue effect was histopathologically assessed by H-E stain, and
      the action mechanism of DSG was considered by immunohistochemical stain using
      monoclonal antibodies, which were against CD4 positive cells, CD8 positive cells,
      and macrophages. In result, the rescue effect of DSG was significant in all
      groups, in comparison with controls, which had no immunosuppression. And the
      rescue effect of group B was superior to group A. We also found using a
      immunohistochemical technique, that DSG inhibited the accumulation of CD4 and CD8
      positive cells. We concluded the rescue effect of DSG for acute rejection on HTX
      was significant, especially in 10 mg/kg/day even in the severe rejection. And the
      suppression of helper and cytotoxic T cells accumulation might be one of the
      action mechanisms of DSG.

PMID- 8308385
TI  - [Reoperation with a bifurcated nonvalved extracardiac conduit for stenosis of the
      valved conduit and the pulmonary bifurcation after a Ross-Rastelli operation].
AB  - We report a case of successful reoperation with a bifurcated nonvalved
      extracardiac conduit for stenosis of the valved conduit and the pulmonary
      bifurcation after a Ross-Rastelli operation. The patient was 11-year-old female,
      who had undergone Ross-Rastelli operation with a 16 mm Carpentier-Edwards valved
      conduit for pulmonary atresia with ventricular septal defect at six year-old
      following Blalock-Taussig shunt at four year-old. She required reoperation for
      progressive right heart failure due to stenosis of the valved conduit and the
      pulmonary bifurcation. The reoperation was performed under cardiopulmonary bypass
      with aortic crossclamp. The stenosed valved conduit placed between the right
      ventricle and the right pulmonary artery was removed and replaced with 18 mm
      EPTFE graft. Because the direct repair of the pulmonary bifurcation stenosis was
      thought to be difficult, a 12 mm ringed EPTFE graft was anastomosed to the left
      pulmonary artery distal to the bifurcation stenosis as a branch of the 18 mm
      EPTFE main graft. Although transitional heart failure required IABP support in
      her early postoperative course, she subsequently recovered and discharged the
      hospital at the 37th postoperative day. Her right ventricular pressure reduced
      from 105 mmHg to 54 mmHg by the cardiac catheterization. She is now alive and
      well without any complaints.

PMID- 8308386
TI  - [Surgical treatment of traumatic rupture of the bicuspid aortic valve: case
      report].
AB  - A 64-year-old female was admitted to our hospital with the complaints of chest
      oppression and dyspnea, 3 months after the traffic accident. She was operated on
      with the diagnosis of aortic regurgitation and bicuspid aortic valve. The tear of
      aortic valve was detected in the anterior cusp, and the size of the tear was 12
      mm. The aortic valve replacement was performed and her postoperative course was
      uneventful. In the pathological study of the cusps, the tear was originated from
      trauma without inflammatory changes. This is the first report of traumatic
      rupture of the bicuspid aortic valve in Japan.

PMID- 8308387
TI  - [A case of acute retrograde type I dissecting aneurysm of aorta underwent three
      operations].
AB  - A 54-year-old man with an acute retrograde type I dissecting aneurysm of the
      aorta underwent three operations for four years. The first operation was by the
      Collins method, the second was a graft replacement of the descending aorta, and
      the third involved a graft replacement of the ascending aorta and aortic arch,
      revascularization of the aortic branches and replacement of the aortic valve. In
      operations on acute retrograde type I dissecting aneurysms of the aorta, the
      methods of Koster or Collins are in appropriate in cases where sufficient entry
      treatment is impossible, and graft replacement of the ascending aorta at least is
      considered to be necessary.

PMID- 8308388
TI  - [Mediastinal lymph node dissection improves survival rate in N2(-) non-small cell
      lung cancer patients].
AB  - The effect of mediastinal lymph node dissection on survival rate in clinical N2(
      ) non-small cell lung cancer patients was assessed. N2(-) was evaluated by both
      pre-operative computed tomography studies and physical examination during
      surgery. Systematic mediastinal lymph node dissection, including nodes #1, 2, 3,
      3a, 3p, 4, 7, 8 and 9 was performed in 27 patients (T1 or 2, N0 or 1, M0) since
      1987 (dissected group). Survival rate and complications were compared with those
      in 21 patients treated before 1986, in whom mediastinal lymph nodes were not
      dissected (non-dissected group). 1, 3 and 5 year survival rates in the dissected
      group were 92.6%, 74.9%, and 74.9%, respectively, which were significantly higher
      than those in the non-dissected group (71.4%, 61.9% and 41.3%, respectively).
      Mediastinal lymph node metastases were detected histologically found in three
      patients, 11% of the dissected group. Respiratory complications showed a
      significantly higher incidence in the dissected group (p = 0.001). However these
      complications did not increase the mortality rate in that group. Among elderly
      patients over 70 years old (8 patients in the dissected group, 7 in the non
      dissected group), survival rates were similar in the two groups. In conclusion,
      systematic mediastinal lymph node dissection significantly improved the survival
      rate in clinical N2(-) non-small cell lung cancer patients.

PMID- 8308389
TI  - [Anomalous origin of the right pulmonary artery from the ascending aorta: a
      report of eight cases].
AB  - We report eight cases with anomalous origin of the right pulmonary artery from
      ascending aorta. The ages at operation ranged from five days to fifteen years
      (average two years and seven months) with the body weights ranging from 1,610 g
      to 47.5 kg. Two patients underwent a surgical intervention in infancy; one of
      them with the body weight of 1,610 g was the smallest case previously reported in
      Japan. Associated cardiothoracic anomalies were patent ductus arteriosus (PDA) in
      five patients, atrial septal defect (ASD), PDA with ASD, tetralogy of Fallot with
      absent pulmonary valve in each one patient. Preoperative systolic pressure of
      pulmonary trunk were varied 83 to 115 mmHg (mean 94.7 mmHg). The continuity
      between pulmonary trunk and detached right central pulmonary artery was restored
      by a direct side-to-end anastomosis either behind (anatomical route) or in front
      of (non-anatomical route) the ascending aorta in all but one patient. There were
      one operative death and one hospital death. Postoperative pulmonary pressure was
      lower in patients with anatomical route than in patients with non-anatomical
      route. We conclude that successful surgical repair can be achieved by a direct
      anastomosis between abnormal detached central pulmonary artery and pulmonary
      trunk behind the ascending aorta even in infancy or early in childhood.

PMID- 8308390
TI  - [A successful case report of redo composite graft and total aortic arch
      replacement for active prosthetic graft endocarditis].
AB  - A successful redo composite graft and total aortic arch replacement for active
      prosthetic graft endocarditis is reported in the 31-year-old female with Marfan
      syndrome who had undergone Bentall procedure and proximal aortic arch replacement
      for type A acute aortic dissection 21 months previously. Echocardiography
      revealed massive vegetation in the composite graft and left ventricular outflow
      tract, and blood culture suggested Candida endocarditis. The composite graft and
      arch grafts were completely removed, and the reconstruction was carried out with
      a new composite graft using Piehler's technique. Finally, the total aortic arch
      was replaced and the all branches were reconstructed. The post-operative course
      has been uneventful, and she is now doing well 12 months after the operation
      without any evidence of recurrence of endocarditis.

PMID- 8308391
TI  - [Curative report of post sternotomy mediastinitis due to bacterofungal
      infection].
AB  - We describe a 72-year-old patient with mediastinitis caused by Methicillin
      resistant Staphylococcus aureus (MRSA) and Candida albicans after median
      sternotomy who was successfully treated with wound closure with pectoral
      musculocutaneous flap and closed continuous mediastinal irrigation. The
      irrigation device consisted of two pairs of irrigation and suction tubes which
      placed upper and lower half of mediastinum respectively, in which high rate
      irrigation technique (200 ml/h) was employed using 0.01% of Vancomycin
      hydrochloride as a base agent and additional 0.1% of Povidone-iodine in early
      phase and 0.01% of Fluconazole in late phase. After 12-days irrigation, the
      drainage culture turned negative and the wound was healed and tomographically
      granulated. High rate irrigation with sufficient concentration of antimicrobial
      agents selected according to each organism sensitivity could eliminate redundant
      irrigation and contribute to avoid antimicrobial toxication. We experienced also
      another four cases (two caused by MRSA, two caused by Serratia liquefaciens)
      treated successfully with this technique. These results led us to believe that
      continuous mediastinal irrigation technique could be carried out with safe and
      effectiveness so far as high rate irrigation with low concentration of Povidone
      iodine is employed.

PMID- 8308392
TI  - [Current studies on glycosyltransferase genes and their perspective: N
      acetylglucosaminyltransferases III & V].

PMID- 8308393
TI  - [Midkine (MK): a retinoic acid-responsive, heparin-binding growth factor in
      relationship with differentiation, development, cancer and neural function].

PMID- 8308394
TI  - [Regulation of Saccharomyces cerevisiae HSP genes].

PMID- 8308395
TI  - [Display of foreign protein on a coat protein of filamentous phage--phage
      antibody].

PMID- 8308396
TI  - [Biosynthesis of the bFGF binding domains of heparan sulfate-N-deacetylase/N
      sulfotransferase].

PMID- 8308397
TI  - [Structure and regulation of hepatic lipase].

PMID- 8308398
TI  - [Correlation between fetal growth and platelet function in normal pregnancy].
AB  - Various interpretations have been attempted, but no definitive theory has yet
      been established as to the etiology of the low-birth-weight infant. We carried
      out the present study in an attempt to explore the relationship between platelet
      functions and fetal growth during normal pregnancy. For this purpose, we made a
      retrospective study of 130 pregnant women aged 23-35 with no clinical
      abnormalities throughout pregnancy or at delivery. Blood samples were taken at 29
      30 weeks of gestation (referred to as the 2nd trimester) and 37-38 weeks of
      gestation (referred to as the 3rd trimester). The cases studied were divided into
      two groups: i) those with a birth weight of under 2,500g (n = 32), and ii) those
      with a birth weight of over 2,500g (n = 98). In these two groups, we studied the
      platelet functions in maternal blood in the 2nd and 3rd trimesters. The following
      results were obtained: 1) In the 2nd to 3rd trimester, the platelet count showed
      no significant variation with the birth weight. 2) In the 2nd to 3rd trimester,
      the platelet aggregation was found to be moderately depressed in cases with a
      birth weight of under 2,500g, while it was found to be moderately activated in
      cases with a birth weight of over 2,500g. 3) In the 2nd to 3rd trimester,
      platelet factor 4 was significantly lower (p < 0.005) in cases with a birth
      weight of under 2,500g, while it was moderately higher in cases with a birth
      weight of over 2,500g.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308399
TI  - [Advanced system for real-time fetal breathing movements tracking using pulsed
      Doppler ultrasound].
AB  - Utilization of the fetal behavioral information in clinical medicine requires the
      development of an automated monitoring technique. As previously reported, the off
      line signal processing of the low frequency Doppler signals by high accuracy
      displacement estimation made it possible to measure fetal breathing movements
      (FBM). However, there were several problems to solve before clinical application.
      We propose an advanced system that provides real-time calculation. The multi
      channel pulsed doppler device was newly developed by modifying the Doppler
      ultrasound module of the cardiotocograph (CTG). A new signal processing algorithm
      was designed to produce real-time measurements. To improve the resolution, the
      backing module was attached to the probe. On-line signal processing produced a
      successful real-time and continuous calculation of displacement inside tissue. By
      means of an on-line 2/3 Hz high pass filter, the very low frequency noises and
      the artifacts derived from maternal respiration etc. were removed. The
      signal/noise ratio was obviously increased and the waves of fetal tissue
      movements due to FBM were easily recognized in real-time LCD outputs. Although
      there is a limitation in measuring accuracy as far as using modified CTG units,
      the results demonstrate that our system has commendable quality in FBM tracking.

PMID- 8308400
TI  - [Clinical evaluation of sub-zonal insemination in male infertility].
AB  - Two hundred forty-two cases of subzonal insemination (SUZI) were performed in 172
      infertile male patients. Criteria for selection of subjects to receive SUZI were
      as follows; those who had previously failed to achieve fertilization by
      conventional in vitro fertilization (IVF) with normal semen analyses (group 1, n
      = 36), those who had previous fertilization failure in conventional IVF with
      abnormal semen analyses (group 2, n = 49) and those who had not been accepted for
      IVF because of severely abnormal semen analyses (group 3, n = 87). Two to twenty
      spermatozoa were injected into the perivitelline space of metaphase II oocytes.
      Fertilization occurred in 77.3% of patients and 40.9% of 1,220 eggs and 28
      clinical pregnancies were established. There were no significant differences in
      fertilization rates, cleavage rates and embryo transfer rates among the three
      groups. However, the pregnancy rate was significantly lower in group 1 (7.7%)
      than in group 2 (20.0%) and group 3 (14.5%) (p < 0.05). These results indicated
      that SUZI improved the incidence of fertilization in male infertility. However,
      the fact that the lowest pregnancy rate was in group 1 indicates that further
      studies of patients with idiopathic failure of fertilization are needed.

PMID- 8308401
TI  - [Studies on hypogeusia in hyperemesis gravidarum].
AB  - We measured changes in gustatory sensitivities and gustation threshold levels and
      those of some trace elements, vitamin E and lipids in the serum of 38 patients
      suffering from hyperemesis gravidarum, 12 normal pregnant women in the first
      trimester and 22 healthy non-pregnant women by means of filter discs and an
      electrogusto meter (EGM) and we obtained the following results. 1. Gustatory
      sensitivity to sweetness was found to be significantly lowered in the patients
      with hyperemesis gravidarum when tested with filter discs (p < 0.05). 2.
      Gustation threshold levels were significantly lowered in the patients with
      hyperemesis gravidarum and the normal pregnant women tested with the EGM (p <
      0.01). 3. There was considerable heterogeusia of women in the patients with
      hyperemesis gravidarum (p < 0.05). 4. Zn and Mg in serum decreased (p < 0.01),
      but Cu increased significantly in the patients with hyperemesis gravidarum and
      the normal pregnant women (p < 0.01). 5. Total cholesterol and phospholipid in
      serum significantly decreased, but lipid peroxide in serum significantly
      increased in the patients with hyperemesis gravidarum (p < 0.01). These results
      suggested that the gustatory test was helpful in investigating hyperemesis
      gravidarum and that biological defense systems (scavenger systems) to free
      radicals were damaged in patients with hyperemesis gravidarum.

PMID- 8308403
TI  - [A case of spontaneously reduced congenital cystic adenomatoid malformation].

PMID- 8308402
TI  - [Endothelin-1-induced contraction of pregnant rat myometrium: role of platelet
      activating factor].

PMID- 8308404
TI  - [A case of pregnancy after surgery for congenital biliary atresia].

PMID- 8308405
TI  - [Postpartum hemorrhage and disseminated intravascular coagulation].

PMID- 8308406
TI  - [A histopathological study on intraepithelial extensivity of carcinoma in situ of
      the uterine cervix in the period of sexual maturity].
AB  - To investigate intraepithelial extension of CIS, thirty-two cases of carcinoma in
      situ (CIS) of the uterine cervix in the period of sexual maturity were examined
      histopathologically and compared with ten cases of microinvasive carcinoma of the
      uterine cervix (restricted to Japanese criteria). The results were summarized as
      follows. 1) A positive correlation was found between the circular spreads and
      longitudinal ones in the lesion in CIS cases. 2) A positive correlation was found
      between circular spread and the depth of gland involvement in the lesion in CIS
      cases. 3) Circular spread of the lesion in microinvasive carcinoma cases was
      significantly more extended than that in CIS cases. These results suggest that
      CIS in the period of sexual maturity is intraepithelially extensive and that
      there is a high risk possibility of invading stroma when circular spread of the
      CIS lesion is greater than one fourth of the whole circle of the uterine cervix.

PMID- 8308407
TI  - Evaluation of isokinetic hip strength after rotational acetabular osteotomy.
AB  - Fifty-four patients with dysplastic hip and secondary degenerative arthrosis (58
      hips) underwent rotational acetabular osteotomy (RAO) using a conventional
      anterior-posterior method or a new technique involving detachment of the greater
      trochanter. Pre- and postoperative hip abductor strength (HAS) and knee extensor
      strength (KES) were evaluated using an isokinetic dynamometer. Postoperative HAS
      in patients treated by detachment of the greater trochanter reached preoperative
      levels 16 weeks postoperatively. Comparison of the postoperative HAS based on the
      two different surgical approaches showed that RAO by detachment of the greater
      trochanter was superior to the conventional method. Pre- and postoperative HAS
      showed a good correlation. Postoperative improvements in HAS over presurgical
      values were not significant in patients with advanced-stage arthrosis and
      severely dysplastic hips. Preoperative HAS should serve as an index for
      determining whether RAO is undertaken using detachment of the greater trochanter.

PMID- 8308408
TI  - [Roentgenographical and anatomical study of the midcarpal joint--morphology and
      degenerative change of ulnar side].
AB  - The present investigator has studied the following anatomic variations and
      degenerative changes of the articular cartilage of the ulnar side of the
      midcarpal joint: the perforation of the triangular fibrocartilage (TFC), and the
      ruptures of the scapholunate and lunotriquetral interosseous ligaments (S-L lig.,
      L-T lig.). The materials were 127 wrist joints obtained from 66 cadavers (age 32
      95, average age 74) and were studied radiographically and anatomically. Two types
      of the ulnar side of the midcarpal joint were classified radiographically and
      anatomically. In the first type, there was no articulation present between the
      hamate and the lunate in 42.5% of the dissected specimens. In the second type,
      there was an articulation present between the hamate and the lunate in 57.5% of
      the dissected specimens. Wrists of the second type correlated significantly with
      the ulnar shift ratio of lunate on the radiographical measurement (p < 0.01).
      Significant cartilage erosion and exposed subchondral bone were found at the
      joints of the second type. There was no correlation between the TFC perforation,
      the carpal interosseous ligament ruptures and degenerative changes of the
      articular cartilage of the ulnar side of the midcarpal joint.

PMID- 8308409
TI  - [Evaluation by microneurography of muscle sympathetic nerve activity in
      myelopathic patients].
AB  - The purpose of this study was to observe the functional condition of the muscle
      sympathetic nerve activity (MSNA) in nine patients with mild myelopathy for which
      surgery was indicated [mean score 14/17 by Japanese Orthopaedic Association (JOA)
      cervical myelopathy and 7/11 for thoracic myelopathy]. The MSNA was obtained from
      the tibial nerve at the popliteal fossa by microneurography. The resting
      activities and the responses during handgripping were analyzed and compared with
      those of a control group of nine healthy volunteers and patients with disorders
      unrelated to myelopathy. The MSNA with the subjects supine was recorded first at
      rest for 5 min. (rest period), next during exertion of 20% of the maximum
      voluntary handgripping power for 5 min. (handgripping period), and last at rest
      for 5 min. (recovery period). The number of MSNA bursts per min. (burst rate) in
      the group with myelopathy was more than that in the control group (p < 0.05) in
      all three periods. The response by MSNA to handgripping in the group with
      myelopathy was higher than that in the control group at the start of handgripping
      (p < 0.01), and tended to be higher even 5 min. after handgripping ended. The
      results appeared to demonstrate that MSNA of patients with mild myelopathy for
      which surgery is indicated is increased in the lower extremities.

PMID- 8308410
TI  - [Experimental study on cryopreservation and intramuscular allografting of
      vertebral body and disc units].
AB  - This study investigated optimal conditions for preservation and intramuscular
      allografting of vertebral body and disc units. First, thirty-one vertebral body
      and disc units were removed from rabbits and divided into three groups: a slow
      freezing group, a quick freezing group, and a fresh non-freezing group. In the
      slow freezing group, disc units were slowly cryopreserved by decreasing
      temperatures from 4 to -80 degrees C using a program freezer. In the quick
      freezing group, they were rapidly cryopreserved by freezing to -80 degrees C
      without a program freezer. Second, to determine favorable duration of immersion
      in cryoprotectant (10% dimethyl sulfoxide), another 20 vertebral body and disc
      units were divided into four groups: immersed at 4 degrees C for 30, 90, 240 and
      1440 minutes. After immersion, they were cryopreserved slowly using a program
      freezer. These disc units were thawed and examined histologically and
      biochemically. In the slow freezing group, both cell number in the anulus
      fibrosus and the value of 35SO4 incorporation in the disc were higher than those
      in the quick freezing group, and the disc viability of the 90-minute group was
      the highest. On the basis of these experiments, vertebral body and disc units
      were grafted into the back muscles of rabbits. To investigate the viability of
      the disc after allografting, another 38 specimens were grafted into the back
      muscles and examined after 4 or 12 weeks. The values for 35SO4 incorporation of
      each group at 4 weeks were about 80% of the pre-grafting level and those at 12
      weeks were about 60%, and the viability of discs maintained. There were no
      significant differences between the slow freezing group, the quick freezing
      group, and the fresh non-freezing group after grafting. Further study is needed
      to determine a method in maintaining viability of the disc after grafting.

PMID- 8308411
TI  - [Clinicopathological study of Ewing's sarcoma and primitive neuroectodermal
      tumor].
AB  - A comparative study concerning the histogenesis of Ewing's sarcoma and its
      relationship with peripheral primitive neuroectodermal tumor (PNET) was
      undertaken using histological, immunohistochemical and ultrastructural
      techniques. The cases studied included 22 Ewing's sarcomas, 17 (ganglio)
      neuroblastomas, 3 peripheral PNETs, 1 peripheral neuroblastoma, 1 Askin's tumor
      and a case in which it was difficult to distinguish between Ewing's sarcoma and
      neuroblastoma. Almost all the cases of Ewing's sarcoma showed neural
      differentiations. Immunohistochemical study using antibodies for neuron-specific
      enolase, protein gene product 9.5, Leu 7 and neurofilament (200 kD) was most
      useful for examining the neural differentiation of these tumors. These results
      suggest that Ewing's sarcoma is in a broad sense one of such peripheral PNETs as
      (ganglio) neuroblastoma, peripheral neuroblastoma and Askin's tumor.

PMID- 8308413
TI  - [Oral rehabilitation in occlusal treatment].

PMID- 8308412
TI  - Longitudinal study of in vivo bone mineral changes in rats using dual X-ray
      absorptiometry--effect of ovariectomy and prednisolone.
AB  - Longitudinal bone mineral measurement was performed by dual X-ray absorptiometry
      (DXA) in fifty 14-week-old Wistar rats divided into the following five groups:
      ovariectomized (OVX); sham-ovariectomized (SHAM); ovariectomized with release of
      proximal tail muscles (OVX + MR); prednisolone-administered (PDN); and saline
      administered (control). Bone mineral density (BMD) was measured at the skull,
      distal femur, proximal tibia, and caudal vertebrae at 4, 8, 12, 16, 20, and 24
      weeks after surgery or onset of administration. This in vivo DXA technique
      accurately showed correlation with the ash weight (r = 0.912-0.971), with a
      precision error of 1.01-2.05%. In the OVX group, the percent changes in distal
      femoral BMD and proximal tibial BMD were -7.6% and -5.3% at four weeks, followed
      by a gradual increase toward the initial value by 12 weeks. On the other hand,
      both OVX and SHAM rats gained BMD of the skull and caudal vertebrae. OVX+MR rats
      also gained BMD of the caudal vertebrae. Release of proximal tail muscles only
      had no significant effect on bone mineral of the caudal vertebrae. Prednisolone
      had no significant effect on bone mineral at any site.

PMID- 8308414
TI  - [Histomorphometric study on age-, diet- and teeth loss-related changes in rat
      condyle].
AB  - To elucidate the mandibular morphological changes due to occlusal and masticatory
      alterations in addition to aging, 66 Donryu male rats (30-74 weeks old) were
      divided into three groups, the control group (solid diet), the soft diet group
      (powder diet containing the same components as the solid one from the 43rd week)
      and the molarless group (all molars were removed at 43 weeks and then fed a
      powder diet). The powder diet group and the molarless group were compared with
      the control group by using a handy microscope system with a CCD camera, soft X
      ray pictures and light microscopy. The results obtained are as follows: 1. The
      height of the mandibular ramus, the length and the width of the condyle in the
      experimental group were shorter than that of the control group, showing a
      statistical significance (p < 0.01). 2. Volumetric bone mineral density of the
      condyle measured by the image analyzer system in the experimental group was less
      than that of the control group, showing a statistical significance (p < 0.01). 3.
      Age-related change and chewing style-related alterations were observed in the
      condylar cartilage area. These findings suggested that the bone remodeling in the
      condyle of aged rats was considerably influenced by occlusal and masticatory
      alterations in addition to aging.

PMID- 8308415
TI  - [Questionnaire about dental health in new university students].
AB  - A questionnaire about dental health was given to 6846 new students in the
      University of Tokyo. The results were as follows: 1. 5.3% of students had
      experienced periodontal diseases. The percentage of students with gingival
      bleeding was 20.7%. 2. Most of the students brushed their teeth 3 minutes at a
      time, 2 times a day. 3. 11.5% of the students had experienced orthodontic
      treatments. The percentage of female students was significantly higher than the
      percentage of male students. 4. 0.9% of the students had experienced TMJ
      disorders. TMJ symptoms were noted in 9.7%. 5. More than 90% of the students
      usually chewed on both sides of the mouth.

PMID- 8308416
TI  - [Histological studies on growth and function of condylar process in rat
      mandible].
AB  - The purpose of this study was to investigate the growth direction and the
      function of the mandibular condyle with the observations of the bone structure.
      Seven week-old rats were used as materials and the condylar processes were
      studied by macroscopic, light microscopic and electron microscopic observations.
      The results were as follows: 1. Many types of bone of different degree of
      calcification and differentiation were observed in the condylar processes. The
      calcified cartilage and immature bone, which were highly calcified, function as
      the core of bone trabeculae and compact bone. Each core was surrounded by other
      types of bone, and then, it seemed that some of these types of bone gave the
      characteristics of stiffness and flexibility to the bone trabeculae and compact
      bone. 2. The bone trabeculae indicated the rational arrangements in the condylar
      process, and as a result, the pressure from the mandibular fossa was transmitted
      to the compact bone efficiently in the masticatory movement. 3. The condylar
      processes in these week-old rats were growing only backward. 4. It seemed that
      the function as the articular head was enhanced mainly after seven week-old
      though the condylar process grew while it was functioning until this stage.

PMID- 8308417
TI  - [Fluorescent labelling of rhodamine-labelled albumin in rabbit incisor dentine].
AB  - Incorporation of rhodamine-labelled serum albumin (R-ALB) into the developing
      dentine was investigated by fluorescent microscopy. Male Japanese white rabbits
      were injected with R-ALB at a dose of 50 mg/kg and the undecalcified section of
      the incisor dentine was obtained 11 days after the injection. The orange-red
      fluorescent labelling of R-ALB was observed in the internal dentine. The
      labelling consisted of several periodic stripes and decreased its intensity
      toward the predentine-dentine junction. Serum concentration of R-ALB rapidly
      decreased after the injection and 10% of the initial value was present after 12
      hours. The concentration gradually decreased thereafter. No relationship was
      observed between the fluorescent labelling pattern and the change in the
      concentration of serum R-ALB. These results suggest that R-ALB fluorescent
      labelling is related to the diurnal dentine formation by the odontoblasts in the
      rabbit incisor.

PMID- 8308418
TI  - [Clinical evaluation of hydroxyapatite-coated titanium artificial tooth root].
AB  - The present study was aimed at evaluating the clinical usefulness of a new type
      of dental implant, one piece-type artificial root made of a titanic core coated
      with HAp by plasma-spray coating. A total of 227 artificial roots were implanted
      in 78 healthy subjects (44 females, 34 males) ranging in age from 17 to 74 years.
      Each of them was examined on several given occasions by both radiography and a
      method used in periodontal disease screening. Prognostic observation lasted up to
      4 years and 3 months. No implants were rejected in 77 subjects, although marked
      mobility of the implants resulted in their withdrawal in 1 subject (2 implants).
      They were functioning favorably during the study period, affording great
      satisfaction to the subjects. No side effects were found in any of the subjects
      excluding one case of oral lichen planus in which the presence of a direct cause
      effect relation remained unclear. From the above results, we conclude that this
      new type of artificial root is of extremely high clinical use.

PMID- 8308419
TI  - [Epidemiological study on distribution of plaque, calculus and gingivitis among
      Nigerian people].
AB  - In 1991, dental health examination was carried out in Nigeria: ILE-IFE (urban)
      and Ashipa (rural) located in the southwest of Nigeria. The number of the
      subjects was 205 (aged 8, 10, 12) in ILE-IFE and 511 (aged 8, 10, 12, 15 to 75)
      in Ashipa. The purpose of this study is to clarify the distribution of plaque,
      calculus and gingivitis and to reveal the correlation between the plaque score
      (DI-S, OHI-S), calculus score (CI-S, OHI-S) and gingivitis score (GI) among the
      Nigerian by age. Results were as follows: 1. In the comparison between urban and
      rural schoolchildren, CI-S was higher in the rural children statistically but DI
      S was not. This evidence is to be expected as a consequence of using PACO
      (traditional twig) for tooth brushing, because 73.1% of rural children were using
      the PACO whilst 92.1% of urban children were using the tooth-brush. 2. Because of
      the poor oral cleanliness using PACO, the changing pattern of DI-S, CI-S and GI
      by age could be natural and physiological. 3. DI-S and CI-S among the rural
      people were of a high level in the children 8 and 10 years of age and decreased
      to the bottom level in the 20's. After the lowest scores in the 20's, these
      increased with age. 4. The correlations between DI-S and GI were higher in the
      young people than in the elder people.

PMID- 8308420
TI  - Silicone synovitis. The current role of silicone elastomer implants in joint
      reconstruction.

PMID- 8308421
TI  - Silastic implants of the scaphoid and lunate. A long-term clinical study with a
      mean follow-up of 13 years.
AB  - 39 implant replacement arthroplasties were reviewed with a mean follow-up of 13
      years. The study includes nine cases of partial replacement of the proximal pole
      of the scaphoid, 16 cases of total replacement of the scaphoid and 14 cases of
      replacement of the lunate. In 33 cases the conventional silicone elastomer (CSE)
      was used and in six the high performance elastomer (HP). Subjective, clinical and
      radiological evaluations gave different results. Respectively the results were
      excellent in 41, 23 and 5%, satisfactory in 41, 49 and 39% and poor in 18, 28 and
      56% of the cases. Lytic lesions in carpal and/or pericarpal bones were present in
      all except two cases. Study of the X-rays chronologically revealed that they
      increased in number and size. Six cases had their implant removed. All had
      histologically proven silicone synovitis. A major secondary operation has been
      performed or is foreseen in all cases except one. We do not recommend implant
      replacement arthroplasty for the scaphoid or the lunate bone.

PMID- 8308422
TI  - Metacarpophalangeal joint arthroplasty based on the osseointegration concept.
AB  - The osseointegration concept has been used for fixation of 68 MP joint
      endoprostheses in 31 patients operated on at the Department of Hand Surgery,
      Malmo General Hospital during the period 1988-1992. The indications were
      rheumatoid arthritis (50 joints), primary osteoarthrosis (three joints), post
      traumatic osteoarthrosis (three joints), post-traumatic osteoarthrosis (five
      joints), post-infectious osteoarthrosis (seven joints) and joint deformities
      secondary to spastic conditions (three joints). The average follow-up time was
      2.5 years (6-54 months). The surgical procedure included resection of the joint
      followed by introduction of screw-shaped titanium fixtures into the bone marrow
      cavities of the metacarpal and the phalangeal base. Rheumatoid cases usually
      required grafting of cancellous bone and marrow from the iliac crest. At the same
      time a flexible constrained silicone spacer was connected to the titanium
      fixtures in such a way as to allow later replacement of the spacer if accessory.
      The average active range of motion (ROM) was 57 degrees in the rheumatoid cases
      and 50 degrees in all cases. Radiological and clinical osseointegration occurred
      in every case, and there were no clinical signs of loosening. In four cases (6%)
      there was a fracture of the joint mechanism. Patient satisfaction was high, with
      pain relief, increased range of motion, improved hand function and good cosmetic
      appearance.

PMID- 8308423
TI  - Tendon ball interposition arthroplasty for traumatic ankylosis of the MP joint.
      Preliminary reports of two cases.
AB  - Two cases of traumatic ankylosis of the MP joint were treated by tendon ball
      interposition arthroplasty. Enough mobility for pinch and grasp was obtained at
      follow-up.

PMID- 8308424
TI  - Irreducible MP joint dislocation due to entrapment of FPL.
AB  - A case of irreducible dorsal dislocation of the first MP joint is presented. The
      tendon of FPL was trapped dorsal to the metacarpal head, and open reduction was
      necessary.

PMID- 8308425
TI  - The range of motion of the MP joint of the thumb following operative repair of
      the ulnar collateral ligament.
AB  - The range of motion of the MP joint of the thumb following repair of the ulnar
      collateral ligament has been compared with the range of motion of the uninjured
      thumb. By making this comparison we conclude that there is no good evidence that
      joint stiffness is a common post-operative complication.

PMID- 8308426
TI  - Hand injuries on artificial ski slope.
AB  - 50 consecutive patients with injuries due to skiing on an artificial ski slope
      were seen in our emergency department over a 16-month period; 76% of these
      involved the hand or wrist. 52.5% of hand lesions were fractures and only one
      third of the first ray injuries were sprains of the ulnar aspect of the MP joint.
      These data significantly differ from those known for skiing on snow.

PMID- 8308427
TI  - The doorstop procedure. A technique for treating unstable fracture dislocations
      of the proximal interphalangeal joint.
AB  - The unstable fracture dislocation of the proximal interphalangeal joint remains a
      difficult injury to manage despite the availability of a wide variety of
      treatment options. We describe a simple alternative method of treatment called
      the doorstop procedure.

PMID- 8308428
TI  - Imaging the position of a screw within the scaphoid. A clinical, anatomical and
      radiological study.
AB  - In an audit of 68 scaphoid fractures with delayed and non-union that had been
      internally fixed using the Herbert bone screw, it was found that 39 had a
      significant fault in screw position. Poor intra-operative imaging was a major
      contributing factor. An anatomical and radiological study was therefore performed
      to evaluate which views were necessary in order to be confident about screw
      position. We recommend a minimum of four views. To display the proximal pole, an
      ulnar deviated postero-anterior (PA) view and true lateral; and to display the
      distal pole, a semi-pronated and semi-supinated view.

PMID- 8308429
TI  - Scapho-lunate diastasis in fractures of the distal radius. Pathomechanics and
      treatment options.
AB  - The concurrence of scapho-lunate diastasis and distal radial fractures is now
      well established. External fixation is considered to be one of the best methods
      of treating distal radial fractures, but in the presence of ligament injury,
      distraction fixation may lead to carpal instability and chronic wrist pain. We
      have reviewed existing English literature and analyzed possible mechanisms of
      injury, and offer some suggestions towards treatment of this combination of
      injuries.

PMID- 8308430
TI  - The isolated scapho-trapezio-trapezoid ligament injury. Diagnosis and surgical
      treatment in four cases.
AB  - Isolated injuries of the scapho-trapezial ligament complex are not well
      recognized. The ligament complex comprises the stout scapho-trapezial ligament,
      the floor of the flexor carpi radialis (FCR) tendon sheath and the scapho
      capitate ligament. Between August 1991 and May 1992, we diagnosed and treated
      four cases of partial chronic post-traumatic lesions of this ligament complex.
      There was chronic pain at the base of the thenar eminence and instability of the
      thumb-index-middle finger pinch. Standard X-rays were normal. The diagnosis of
      ligament rupture was confirmed by mid-carpal arthrography showing filling of the
      sheath of FCR tendon. Surgical exploration showed complete rupture of the tendon
      sheath of FCR in two cases, associated in the other two cases with complete
      rupture of the scapho-trapezial ligament. Direct repair of the ligamentous
      elements was performed in all cases. The tendon of FCR was sutured to the
      tubercle of scaphoid to protect and to reinforce the ligament repair. The
      patients have been followed-up for between 6 and 12 months. All four patients
      recovered normal pinch strength to the middle finger. One patient suffered from
      chronic pain at work.

PMID- 8308431
TI  - Aneurysmal bone cysts in the hand treated by free non-vascular transfer of
      metatarsal or proximal phalanx from the foot.
AB  - Two cases of aneurysmal bone cyst in the hand are reported. In one case the
      entire first metacarpal was resected and grafted using the fourth metatarsal. In
      the second case diaphysectomy of the middle phalanx of the index digit was
      performed, and the proximal phalanx of the second toe was used as graft.
      Satisfactory length and function were maintained, the grafts remained viable and
      there was no donor site morbidity. Transplant of a metatarsal or toe phalanx to
      the hand, as a free non-vascularized graft, is a relatively straight forward
      operation, requires minimal refashioning of the graft, provides articular
      surfaces for joint reconstruction and leaves little donor site morbidity.

PMID- 8308432
TI  - Eosinophilic granuloma of the hand.
AB  - The first reported case of eosinophilic granuloma of the hand is presented. A
      slowly expanding lesion of the right third metacarpal shaft was treated by biopsy
      and curettage. Histological examination confirmed the presence of eosinophilic
      granuloma. A bone scan showed that it was a solitary lesion. There has been no
      evidence of recurrence of the lesion during follow-up. Eosinophilic granuloma is
      a rare disease of the mononuclear phagocyte system, representing one of the
      clinical manifestations of Langerhans-cell histiocytosis. The lesions are usually
      associated with the skull, femur, mandible and ribs; this condition has not been
      previously reported in the hand.

PMID- 8308433
TI  - Ultrasonography of a subungual glomus tumour.
AB  - Glomus tumour is sometimes difficult to diagnose accurately before surgery. We
      report a case where ultrasonography confirmed the presence and precise location
      of a lesion before surgery.

PMID- 8308434
TI  - Unilateral carpal tunnel syndrome and space-occupying lesions.
AB  - To assess the association between unilateral carpal tunnel syndrome and space
      occupying lesions, 128 patients have been reviewed. They were divided into
      bilateral, subclinical (unilateral signs and symptoms, and bilateral slowing in
      the median nerve conduction) and unilateral carpal tunnel syndrome. Space
      occupying lesions were investigated on the basis of physical examination and
      wrist imaging using plain radiographs and ultrasonograms. Of 20 patients with
      unilateral carpal tunnel syndrome, space-occupying lesions were found in seven
      (occult ganglion in five and occult calcified mass in two). In contrast, none of
      89 patients with bilateral carpal tunnel syndrome and 19 with subclinical carpal
      tunnel syndrome had space-occupying lesions. We conclude that careful examination
      and wrist imaging on suspicion of local pathology, especially a space-occupying
      lesion, are needed when the condition is unilateral and the aetiology is not
      clear from the history and on physical examination.

PMID- 8308435
TI  - Grip strength following carpal tunnel decompression.
AB  - To monitor the effect of open carpal tunnel decompression on grip strength in the
      hand, a prospective study was made of 25 patients undergoing a total of 31
      operations. Hand grip, key pinch and pulp-to-pulp pinch strengths were measured
      pre-operatively and at regular intervals until 1 year following operation. At
      that time there was no significant difference in the hand grip and pulp-to-pulp
      pinch strengths compared to their pre-operative values, but the key pinch in
      females showed a marginally significant reduction (P = 0.04) compared to the pre
      operative value.

PMID- 8308436
TI  - Posterior interosseous nerve compression due to an enlarged bicipital bursa
      confirmed by MRI.
AB  - Posterior interosseous nerve compression is a well-described clinical entity with
      many aetiologies. Fewer than 12 documented cases of the condition due to an
      enlarged bicipital bursa exist in the literature. We describe a case in which
      magnetic resonance imaging (MRI) was used in the preoperative assessment of a
      mass in the proximal forearm with a clinical diagnosis of partial posterior
      interosseous nerve compression.

PMID- 8308437
TI  - Posterior interosseous nerve paralysis related to focal radial nerve constriction
      secondary to vasculitis.
AB  - A case of posterior interosseous nerve paralysis is reported with discussion of
      some characteristics that appear to distinguish it from entrapment neuropathy and
      neuralgic amyotrophy. The surgical implications are also discussed. More than ten
      similar cases have been reported, but the pathogenesis of this condition is still
      controversial. The patient presented with posterior interosseous nerve paralysis
      related to focal radial nerve constriction secondary to vasculitis in the
      perineurium. The constriction site was resected and the radial nerve was sutured.
      The patient recovered completely after 8 months.

PMID- 8308438
TI  - Hypothenar hammer syndrome in workers occupationally exposed to vibrating tools.
AB  - Among 330 vibration-exposed workers, 24 cases of hypothenar hammer syndrome in 29
      hands were diagnosed by arteriography. The right hand was involved in 13, the
      left hand in six, and both hands in five cases. The mean age was 55 years, mean
      duration of vibration exposure 19.4 years, and mean duration of episodic
      Raynaud's phenomenon 6.4 years. The vascular lesions of the ulnar arteries were
      classified into three major types with subtypes. Type 1: stenosis of the
      superficial palmar arch around the hook of the hamate. Type 2a: occlusion of the
      superficial palmar arch around the hook of the hamate. Type 2b: occlusion of both
      superficial and deep palmar arches around the hook of the hamate. Type 3a:
      occlusion of the ulnar artery at the proximal part of the wrist. Type 3b:
      occlusion of the ulnar artery near the wrist with the occlusion of the dorsal
      carpal branch of the ulnar artery.

PMID- 8308439
TI  - The corkscrew sign in hypothenar hammer syndrome.
AB  - Arteriography of an adult manual labourer presenting with numbness and cold
      intolerance in the middle and ring fingers of the right hand demonstrated filling
      defects in the digital arteries of these two fingers associated with a corkscrew
      like configuration of the ulnar artery in Guyon's canal. This arterial segment
      was subsequently excised revealing intramural necrosis and fibrosis and
      nonocclusive intraluminal thrombosis. An arteriogram performed 2 years previously
      for an unrelated condition revealed a similar but less pronounced corkscrew
      configuration of the artery, suggesting that this finding could be a marker for
      arterial injury which may eventually lead to embolization or thrombosis with
      accompanying ischaemic symptoms.

PMID- 8308440
TI  - Response of fingertip circulation to local warming in the injured hand--a study
      using laser Doppler flowmetry.
AB  - A laser Doppler flowmeter was used to assess the fingertip circulation serially
      in 41 patients with various hand injuries. The "flux value" measures the flow of
      red cells across the site of assessment and the "fluctuation" represents the
      pulsatile peak-trough difference in flux value with each cardiac contraction.
      Local temperature at the fingertip was raised stepwise by a special heater
      thermostat from 36 to 44 degrees C. Compared to the normal hand both the flux
      value and fluctuation in the injured hand are smaller at lower temperatures. The
      differences narrow down at higher temperatures and the trend reverses above 42
      degrees C and remains so on cooling. This may represent abnormal sympathetic tone
      in the injured hand.

PMID- 8308441
TI  - Vein grafting with the telescoping anastomotic technique for venous defects.
AB  - The telescoping anastomotic technique was used at both ends of autogenous vein
      grafts bridging a defect in slow-running, vulnerable veins. This was done on left
      epigastric veins of the rat, the central part of which was used as a graft. In
      the right epigastric veins, both the proximal and distal anastomoses were
      repaired using the conventional anastomotic technique. The overall patency rate
      of the grafts repaired with the telescoping anastomotic technique was 27/29
      (93.3%) compared to 17/28 (60.7%) in the conventional group. The telescoping
      technique was also easier to perform than the conventional method.

PMID- 8308442
TI  - Cross thumb transfer.
AB  - Thumb reconstruction following amputation was accomplished by microvascular
      transfer of the thumb from the contralateral paralyzed hand in two cases. The
      appearance and function of the transferred thumbs were excellent and no problem
      was seen in the donor hand.

PMID- 8308443
TI  - Amputations in the treatment of Dupuytren's disease.
AB  - 23 finger amputations in 19 patients operated on for Dupuytren's disease were
      reviewed 6 months to 8.5 years after operation (mean 4 years). The distribution
      of amputations were 17 little fingers and six ring fingers. We found a recurrent
      lack of extension in nine out of 16 finger amputations distal to the MP joint and
      painful neuroma or phantom limb pain in five out of seven little finger
      amputations through or proximal to the MP joint. When amputation in the little
      finger is necessary, disarticulation of the MP joint may be preferable to
      amputation at a more distal level. Alternatives to finger amputation should be
      sought in difficult cases of Dupuytren's disease.

PMID- 8308444
TI  - Closed continuous irrigation as a treatment for infection in the hand.
AB  - A method of closed irrigation has been devised to treat infections in the hand.
      After adequate debridement, two tubes are placed in the infected area, an inlet
      tube and an outlet tube. For a small infection, one tube serves both purposes.
      The wound is closed completely. Irrigation with saline and antibiotic solution is
      continued for 1 week, extended up to 3 weeks in cases of severe infection. This
      method has been applied in 31 cases including pyogenic tenosynovitis, tuberculous
      tenosynovitis, pyogenic arthritis, osteomyelitis, bite injury, crush injury and
      amputation stump infection. Infection healed primarily in 29 cases. Further
      surgery was needed in two cases which healed finally.

PMID- 8308445
TI  - Two-point discrimination tests versus functional sensory recovery in both median
      and ulnar nerve complete transections.
AB  - Transection of both median and ulnar nerves provides an objective model to
      compare sensory and functional recovery. 22 patients were evaluated after nerve
      repair. The mean age was 30 years and the mean time since surgery 80 months.
      Primary direct suture was performed in 15 patients and six grafts were necessary.
      Median nerve suture and ulnar nerve graft were combined in one case. Both sensory
      and functional evaluation were completed. Statistical evaluation analyzed the
      relationship between age, injury location, mechanism, type of rehabilitation and
      the result, and the relationship between two-point discrimination distance (2-PD)
      and the functional score. According to the S0 to S4 grading, only 26.5% (ulnar)
      and 31% (median) of direct suture cases achieved S3+ or more. All nerve grafts in
      adults were poor. A strong relationship was found between two-point
      discrimination distance (moving and static) and the functional result, even after
      multivariate analysis. A modification of the Medical Research Council's
      classification is suggested.

PMID- 8308446
TI  - Interpreting the results of unilateral digital nerve repair.
AB  - We report the results of examination of patients before primary and secondary
      unilateral digital nerve repair. Two-point discrimination was uniformly recorded.
      The results show that significant overlap of adjacent digital nerves is common
      and this has important implications for interpretation of results after repair.
      Recommendations are made regarding the evaluation of outcome following surgery.

PMID- 8308447
TI  - The Hoffmann-Tinel sign. 1915.
AB  - The aim of this article is to show that the well-known Tinel sign is really a
      Hoffmann-Tinel sign. The translation of the two papers of Hoffmann, published in
      the same year that Tinel wrote his article (1915), is completed by a short
      biography of Paul Hoffmann.

PMID- 8308448
TI  - Dupuytren's contracture.

PMID- 8308449
TI  - An epidemiological framework for the formulation of health insurance policy.

PMID- 8308450
TI  - Mandated supervision, monitoring, and therapy of disciplined health care
      professionals. Implementation and model regulations.

PMID- 8308451
TI  - Avoiding discriminatory drug testing practices under the Americans with
      Disabilities Act.

PMID- 8308452
TI  - 1992 Le Tourneau Award. Problems with pharmaceutical regulation in the United
      States. Drug lag and orphan drugs.

PMID- 8308453
TI  - Castration of sexual offenders. Legal and ethical issues.

PMID- 8308454
TI  - Excitatory amino acids and hypothalamo-pituitary-gonadal function.

PMID- 8308455
TI  - Localization, characterization and activity of pituitary adenylate cyclase
      activating polypeptide in the frog adrenal gland.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has recently been
      isolated from the frog brain and the sequence of the peptide appears to be
      strikingly similar to that of mammalian PACAP. In the present study, we have
      investigated the localization of PACAP in the frog interrenal (adrenal) gland by
      immunocytochemistry using antisera directed against PACAP 38 or PACAP 27. Two
      types of PACAP-immunoreactive fibres were observed: thick varicose fibres
      coursing between adrenal cells and thin processes located in the walls of blood
      vessels irrigating the gland. Bilateral transection of the splanchnic nerves did
      not affect the intensity and distribution of PACAP immunoreactivity. The mean +/-
      S.E.M. concentration of PACAP, measured by radioimmunoassay in crude adrenal
      extracts, was 0.65 +/- 0.16 nmol/g wet tissue. Two molecular forms of PACAP in
      the adrenal gland were characterized by reversed phase high-performance liquid
      chromatography combined with radioimmunoassay quantification. The elution
      profiles revealed the existence of two peaks exhibiting the same retention times
      as synthetic frog PACAP 38 (fPACAP 38) and PACAP 27, the predominant form being
      PACAP 38. The possible involvement of PACAP in the regulation of adrenal
      steroidogenesis was investigated in vitro using a perifusion system for frog
      adrenal slices. Graded doses of fPACAP 38 (0.1-10 mumol/l) increased the
      secretion of both corticosterone and aldosterone in a dose-dependent manner.
      Administration of repeated pulses of fPACAP 38 (1 mumol/l), at 120-min intervals,
      led to a reproducible stimulation of corticosteroid secretion without any
      tachyphylaxis. Prolonged infusion (2 h) of the peptide induced a rapid increase
      in corticosterone and aldosterone output, followed by a gradual decline in the
      secretion rate, suggesting the occurrence of a desensitization phenomenon.
      Synthetic porcine vasoactive intestinal peptide, which is structurally related to
      PACAP, was about ten times less potent than fPACAP 38 in stimulating
      steroidogenesis while the [Des-His1]-fPACAP 38 analogue was 100 times less
      effective. These results demonstrate that a peptide closely related to fPACAP 38
      is present in fibres innervating the frog adrenal gland and could participate in
      the regulation of corticosteroid secretion, particularly during neurogenic
      stress.

PMID- 8308456
TI  - Preferential increase in prostaglandin endoperoxide H synthase compared with
      lipoxygenase activity in sheep placenta and amnion at term pregnancy and after
      intrafetal glucocorticoid administration.
AB  - Prostaglandins (PGs) have been implicated as stimulants to myometrial
      contractility at parturition in many species. To determine whether the increased
      production of PGs at parturition reflects a general increase in the metabolism of
      arachidonic acid or a specific increase in PG endoperoxide H synthase (PGHS)
      compared with lipoxygenase activities, and to determine intrauterine sites of
      these activities, we examined the metabolism of [3H]arachidonic acid by
      homogenates of placenta, amnion and chorion from sheep at days 78-80, 100-105,
      135-140 of pregnancy and at term (day 145). Tissues were also obtained from
      fetuses at day 125; four of these were infused for 84 h with cortisol and four
      were used as saline-treated controls. The endogenous arachidonic acid content at
      the start of incubation was measured by capillary gas chromatography. Radioactive
      metabolites were separated and quantified by reverse-phase high-pressure liquid
      chromatography. At each gestational age arachidonic acid was converted to PGs,
      leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs). Conversion to PGs
      was greater in amnion than in chorion or placenta between days 78 and 140. The
      formation of PGs rose in placenta at term to a mean value twice that of amnion
      and ten times that of chorion. In amnion, the ratio of PG:LT rose significantly
      at term relative to 100-140 days of gestation. In placenta, the ratio of PG:LT
      produced from arachidonic acid and the ratio of total PGHS:lipoxygenase products
      rose significantly at term. In the day-125 fetuses treated with cortisol there
      was a significant increase in PG production relative to that in control fetuses
      infused with saline in placenta, amnion and chorion; the placenta and amnion
      being the major sites of PG production. Production of LTs and HETEs also rose
      significantly in the chorion and the placenta relative to controls. In both the
      placenta and the amnion there was a significant increase in the ratio of total
      PGHS to lipoxygenase products formed. We conclude that at term labour and in
      labour induced by intrafetal cortisol infusion, the placenta is the major site of
      arachidonic acid metabolism, and that there is a preferential increase in the
      formation of PGs over lipoxygenase products. These results are consistent with
      the suggestion that there is an increase in the expression or activity of PGHS in
      the placenta of sheep in late pregnancy.

PMID- 8308457
TI  - The influence of the maternal thyroid hormone environment during pregnancy on the
      ontogenesis of brain and placental ornithine decarboxylase activity in the rat.
AB  - The influence of maternal hypothyroxinaemia on early brain and placental
      development was examined in a partially thyroidectomized (parathyroid-spared; TX)
      rat dam model. Ornithine decarboxylase (ODC) specific activity, along with more
      general indices of cell growth, were determined in prenatal whole brain (at 15,
      19 and 22 days of gestation), postnatal brain regions (at 5, 10 and 14 days) and
      placenta. Maternal hypothyroxinaemia resulted in reductions in fetal body weight,
      brain weight, brain DNA content and brain total protein content at 15 days of
      gestation; the latter effect persisting until 19 days of gestation. Further
      changes in brain cell growth were observed near term, when an increase in the DNA
      concentration was accompanied by a decrease in the total protein:DNA ratio.
      Growth of the postnatal brain regions appeared normal, with the exception of an
      isolated increase in the protein content of the cerebellum at postnatal day 5.
      Determination of the specific activity of brain ODC revealed a complex pattern of
      change in the progeny of TX dams, superimposed upon the normal ontogenetic
      decline. In the fetal brain, activity was initially deficient at 15 days of
      gestation but was increased at 22 days of gestation relative to controls. The
      compromise extended into the postnatal period; ODC specific activity being
      transiently reduced in the brainstem, the subcortex and the cerebral cortex.
      Placental development was less consistently affected; wet weight, gross indices
      of cell growth (DNA content, DNA concentration, total protein:DNA ratio) and ODC
      specific activity were all normal in the TX dam. However, cytosolic and total
      protein concentrations were reduced at 15 and 19 days of gestation
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308458
TI  - Dopamine is taken up from the circulation by, and released from, local
      noradrenergic varicose axon terminals in zona glomerulosa of the rat: a
      neurochemical and immunocytochemical study.
AB  - The effect of supramaximal electric field stimulation on [3H]dopamine (DA)
      release by rat adrenal capsule-glomerulosa preparations was studied using a micro
      volume perfusion system. When the tissues were preloaded with [3H]DA, a
      considerable amount of [3H]DA and [3H]noradrenaline (NA) were released in
      response to field stimuli. Reserpinization, calcium removal or tetrodotoxin
      blocking of Na+ influx all completely inhibited the stimulation-evoked release of
      DA/NA, indicating that the radioactivity released is of neuronal and vesicular
      origin. In the adrenal cortex, a substantial proportion of tyrosine hydroxylase
      and dopamine-beta-hydroxylase immunoreactive nerve fibres and varicosities were
      observed around the zona glomerulosa. DA-containing nerves were not seen in the
      adrenal cortex; however, the same immunocytochemical procedures clearly
      demonstrated dopaminergic nerve cells and fibres in the substantia nigra and the
      striatum respectively, and cells of the adrenal medulla. Like the NA release from
      noradrenergic varicosities in the zona glomerulosa, the DA release from
      noradrenergic endings is not subject to negative feedback modulation through DA2
      receptors since apomorphine, a DA2-receptor agonist, and sulpiride, a selective
      DA2-receptor antagonist, failed to affect the release. After in-vivo i.v.
      administration of [3H]DA, the glomerulosa content of DA and NA and the in-vitro
      release of [3H]DA and [3H]NA of zona glomerulosa both increased, indicating that
      the local varicose axon terminals were able to accumulate DA from the
      circulation, convert it into NA and release it in response to neural activity.
      This local arrangement of noradrenergic axon terminals, able to take up DA from
      the circulation and release it or convert it into NA, provides the possibility of
      a fine tuning of local circulation and aldosterone synthesis in the zona
      glomerulosa.

PMID- 8308459
TI  - Rat placental lactogen-I binds to the choroid plexus and hypothalamus of the
      pregnant rat.
AB  - Recent findings suggest that placental lactogen has a role in the regulation of
      hypothalamic function during pregnancy. To explore the mechanisms by which
      placental hormones may exert effects in the maternal central nervous system, we
      have examined the binding of rat placental lactogen-I (rPL-I) to brain slices
      from pregnant rats at mid- and late gestation. The binding of rPL-I to maternal
      rat brain was compared with that of human GH (hGH). Radiolabelled rPL-I bound
      specifically to ependymal cells of the choroid plexus in the lateral ventricles
      and in the roof of the third ventricle. The binding of 125I-labelled rPL-I was
      inhibited by unlabelled rPL-I, hGH or rat prolactin but not by rat GH, indicating
      that rPL-I and rat prolactin interact with a common binding site in maternal rat
      brain. Radiolabelled hGH bound to the choroid plexus and to ependymal cells
      lining the third ventricle in the region of the arcuate nucleus. In addition, hGH
      bound specifically to the ventromedial nuclei and to the medial preoptic area of
      the hypothalamus. The binding of radiolabelled hGH to all brain regions was
      inhibited by unlabelled rPL-I as well as hGH, indicating that rPL-I competes for
      lactogenic binding sites in the hypothalamus as well as the choroid plexus of the
      pregnant rat. These findings suggest potential mechanisms by which placental
      hormones may exert direct effects on the maternal central nervous system during
      pregnancy. The precise functions and roles of the PL-I binding sites in maternal
      choroid plexus and hypothalamus remain to be explored.

PMID- 8308460
TI  - Nutritional regulation of insulin-like growth factor-I mRNA expression in salmon
      tissues.
AB  - In salmonids, nutritional insufficiency leads to retarded growth and reduced
      hepatic GH receptors, but increased circulating GH levels. To understand the
      endocrine mechanism underlying the retarded growth in starved fish better, we
      investigated the effect of food deprivation and refeeding on circulating levels
      of GH and insulin, as well as insulin-like growth factor-I (IGF-I) mRNA
      expression in different tissues of juvenile coho salmon (Oncorhynchus kisutch).
      Deprivation of food for 2-4 weeks resulted in cessation of growth and a
      significant decrease in condition factor (an indicator of fish body shape). No
      difference in circulating insulin or glucose levels were found between starved
      and fed fish, whereas starvation increased the plasma GH levels. After 4 weeks of
      starvation, the plasma GH level rose to 9 ng/ml, which was four times as high as
      that of the fed fish. In spite of elevated circulating GH, hepatic IGF-I mRNA
      levels were significantly reduced after 4 weeks of starvation. No significant
      difference in IGF-I mRNA levels of fed and starved fish was found in other
      tissues, including kidney, spleen, ovary, gill filament and gut. Two weeks of
      refeeding significantly increased hepatic IGF-I mRNA levels and growth and
      reduced plasma GH levels. These results suggest that food deprivation primarily
      reduces IGF-I mRNA expression in the liver which results, most probably, in a
      decline in systemic IGF-I levels and consequently leads to the retarded growth of
      salmon.

PMID- 8308461
TI  - Adrenal progesterone facilitates the negative feedback of oestrogen on LH release
      in ovariectomized rats.
AB  - There is evidence that the adrenals play a role in the regulation of the
      synthesis and release of gonadotrophins in various vertebrates. The aim of this
      study was to determine the part played by adrenal steroids, with special
      reference to progesterone, on the concentration of LH in ovariectomized (OVX) and
      oestrogen-primed rats. OVX rats received a single s.c. injection of vehicle or
      oestradiol benzoate (OB, 20 micrograms/rat). This day was designated as day 0.
      Three or four days later (day 3-day 4), the rats were treated with mifepristone
      (10 mg/kg) or with two doses of progesterone antiserum and blood samples were
      obtained at 13.00 and 18.00 h. OB treatment of OVX rats reduced serum LH at 13.00
      h and 18.00 h on day 3 but only at 13.00 h on day 4. The administration of
      mifepristone at 08.00 h to OVX and oestrogen-treated rats induced a significant
      increase in serum LH at 18.00 h on days 3 and 4, without modifying the values at
      13.00 h. When mifepristone was given at 13.00 h a much larger increase in serum
      LH was obtained at 18.00 h. In OVX and oestrogen-treated rats, adrenalectomy on
      day 2 (08.00-09.00 h) induced an increase in serum LH at 18.00 h similar to that
      observed in the OVX and oestrogen-primed rats after mifepristone treatment. In
      order to determine the specificity of the effect of mifepristone, a group of OVX
      and oestrogen-treated rats was injected with progesterone antiserum at 08.00 and
      13.00 h on day 3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308462
TI  - Prolonged intermittent but not continuous administration of oestradiol-17 beta
      increases bone volume in the rat.
AB  - We have previously found that administration of oestradiol-17 beta (OE2) to
      intact adult female rats of 19 days stimulates cancellous bone formation.
      However, this effect is not observed following longer periods of OE2 treatment,
      suggesting that the responsiveness of the skeleton to oestrogen's anabolic action
      is reduced after prolonged administration. A possible explanation for this is
      that oestrogen also suppresses bone resorption, which is an important stimulus
      for bone formation. We therefore investigated the effect of omitting OE2 for
      short periods, on the proximal tibial metaphysis of intact female rats. We found
      that, unlike continuous treatment with OE2 (40 micrograms/kg) for 56 days,
      omission of OE2 for 4 days out of every 20 was associated with a significant
      increase in cancellous bone volume. Although continuous and intermittent OE2 were
      both associated with a reduction in osteoclast surface, a decrease in the
      proportion of double fluorochrome-labelled surface was only seen after continuous
      OE2 treatment. We then studied the effects of longer periods of OE2 omission by
      giving OE2 (40 micrograms/kg) for three repeated cycles of: (1) OE2 for 16
      days/vehicle for 4 days, (2) OE2 for 12 days/vehicle for 8 days, (3) OE2 for 8
      days/vehicle for 12 days, or (4) OE2 for 4 days/vehicle for 16 days. We found a
      significant increase in cancellous bone volume when OE2 was stopped for either 4
      or 8 days at a time. However, longer periods of OE2 omission did not affect bone
      volume, possibly because these were associated with an increase in bone
      resorption and/or a reduction in bone formation during the OE2-free
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308463
TI  - Stimulation of placental, fetal and neonatal growth by thyroxine administration
      to pregnant rats.
AB  - The effects of daily thyroxine (T4) administration to pregnant rats on the growth
      of their fetuses and placentae were examined. Additional trials examined the
      effect of such treatment on the postnatal growth of the offspring. Injection of
      10 micrograms T4 into the mother caused a tenfold elevation in maternal plasma T4
      concentration, which remained elevated for more than 12 h, but returned to basal
      levels by 24 h after injection. Despite the increase in maternal T4
      concentrations, no increase in fetal plasma T4 was found. A greater weight of
      both the fetuses (20.1%; P < 0.001) and placentae (14.6%; P < 0.05) was found in
      the young of T4-treated mothers compared with those from control mothers at
      delivery by hysterotomy on day 20 of gestation. In trials where mothers delivered
      naturally, birth weights of the young from mothers treated with T4 (10, 20 or 50
      micrograms daily) were also significantly heavier than controls, and continued to
      grow faster postnatally. These data suggest that maternal thyroid hormone status
      is important for fetal growth, and further indicate that stimulation of the
      thyroid hormone axis during pregnancy could provide a method for improving
      postnatal growth.

PMID- 8308464
TI  - A novel angiotensin I isolated from an elasmobranch fish.
AB  - It is believed that the renin-angiotensin system evolved initially in primitive
      bony fishes and is absent from elasmobranchs. We have isolated angiotensin I from
      the incubates of plasma and kidney extracts of an elasmobranch fish, Triakis
      scyllia, using eel vasopressor activity as an assay system. Its sequence was
      determined to be H-Asn-Arg-Pro-Tyr-Ile-His-Pro-Phe-Gln-Leu-OH. Dogfish
      angiotensin I is teleost-like because of an asparagine residue at position 1 but
      it is mammalian-like because of an isoleucine residue at position 5. The unique
      and most important substitution in dogfish angiotensin I is a proline residue at
      position 3 which may cause significant changes in its tertiary structure. A
      glutamine residue at position 9 is also unique among all angiotensin Is sequenced
      to date. Dogfish angiotensin I is more potent than rat angiotensin I in its
      vasopressor activity in the dogfish but the relationship is reversed in the rat.
      Thus angiotensin receptors as well as the hormone molecules appear to have
      evolved during vertebrate phylogeny. Our findings establish the elasmobranch
      renin-angiotensin system and support the hypothesis that the renin-angiotensin
      system is a phylogenetically old hormonal system which plays important roles in
      cardiovascular and fluid homeostasis.

PMID- 8308465
TI  - Suppression of basal secretion of FSH inhibits follicular development and
      maturation during the oestrous cycle of the rat.
AB  - The role of basal FSH secretion during the rat oestrous cycle in regulating
      ovulation was examined by suppressing FSH secretion using charcoal-treated
      porcine follicular fluid (pFF). Although 0.5 ml pFF given at 05.00 and 11.00 h on
      the day of pro-oestrus had no effect on ovulation, 0.5 ml pFF given five times at
      6-h intervals from 11.00 h on dioestrus to 11.00 h on pro-oestrus completely
      eliminated ovulation on the morning of the next oestrus. When 0.25 ml pFF was
      given on the same schedule, all animals ovulated a significantly decreased number
      of oocytes (9.0 +/- 0.8) at the next oestrus. During the period of pFF treatment,
      the number of follicles capable of ovulating in response to human chorionic
      gonadotrophin (hCG) decreased (7.6 +/- 0.7 at 05.00 h on pro-oestrus) and plasma
      levels of oestradiol showed a peak level 6 h later than in controls treated with
      0.5 ml steroid-free porcine serum. Treatment with pFF suppressed plasma FSH
      concentrations in a dose-dependent manner, although plasma LH was inhibited
      irregularly. Supplementary administration of LH throughout the treatment period
      and 0.5 ml pFF resulted in ovulation of one to three oocytes in response to hCG
      in only three out of ten animals. These results suggest that basal secretion of
      FSH during the rat oestrous cycle plays an essential role in follicular
      development and maturation towards ovulation, and that the levels of FSH
      secretion may contribute to the maturation of normal numbers of follicles for
      ovulation.

PMID- 8308466
TI  - Des-acetylated variants of alpha-melanocyte-stimulating hormone and beta
      endorphin can antagonize the mammotrope-recruiting activity of their acetylated
      forms.
AB  - We have previously reported that hypophysial neurointermediate lobe peptides, di
      acetylated alpha-melanocyte-stimulating hormone (di-ac-alpha-MSH) and N
      acetylated beta-endorphin (N-ac-beta-END), can acutely increase the relative
      number of prolactin-secreting cells in anterior pituitary cell cultures from
      ovariectomized rats. Inasmuch as the des-acetylated forms of these peptides (des
      ac-alpha-MSH and beta-END) were not effective in this regard, we concluded that
      acetylation was an absolute requirement for manifestation of the recruitment
      response. The aim of the present study was to determine whether these des
      acetylated variants could antagonize the mammotrope-recruiting activity of their
      acetylated congeners. Treatment of anterior pituitary cell cultures with di-ac
      alpha-MSH and N-ac-beta-END increased the relative amount of prolactin secretors
      above control values. Interestingly, des-acetylated variants of alpha-MSH and
      beta-END blocked the mammotrope-recruitment activity of their respective
      acetylated forms. In addition, beta-END antagonized the mammotrope-recruitment
      activity of di-ac-alpha-MSH while des-ac-alpha-MSH did not attenuate the
      stimulatory effect of N-ac-beta-END. Given that mammotropes maintained in vivo
      are exposed to all these peptides, it is possible that these acetylated and non
      acetylated congeners may act in an opposing manner to regulate dynamic prolactin
      release.

PMID- 8308468
TI  - Serum unmasks the binding of thyroid-stimulating hormone to endogenous and
      transfected receptors: evidence for a soluble form of the receptor in human
      thyroid.
AB  - A specific homologous radioligand receptor assay for thyroid-stimulating hormone
      (TSH) using bovine thyroid membranes was adapted for use with human thyroid.
      Specific 125I-labelled TSH binding was detected in the 3000 g membrane pellet
      from bovine thyroid but predominantly in the 3000 g supernatant of the human
      thyroid homogenate. Both assays required incubation in the presence of 10% serum,
      whilst the assay using human thyroid could only be precipitated using
      polyethylene glycol (PEG). The serum requirement transcended a possible role as
      carrier protein and unmasked specific TSH binding. Molecular sieving determined
      that the active fraction of the serum had an apparent size of 30,000-100,000. The
      requirement for PEG-assisted precipitation of the TSH receptor assay was a
      consequence of the TSH-binding entity from Graves' thyroid behaving like a
      soluble 'receptor': it did not sediment with the membranes, passed a 0.2 microns
      filter and, upon molecular sieving, had an apparent size of 300,000-1,000,000. A
      full-length TSH receptor cDNA was cloned from a human Graves' thyroid library and
      stably transfected cell lines expressing the TSH-receptor protein were
      constructed using human HeLa and murine 3T3 cells. Specific TSH binding was
      unmasked by serum in the human cell lines, as observed for the human thyroid TSH
      receptor, whereas serum hindered TSH binding in the murine cell lines. A soluble
      form of the receptor was not released from the cells and was not produced in
      conditions which demonstrated a soluble receptor-like binding component in human
      thyroid tissue.

PMID- 8308467
TI  - 11 beta-Hydroxylase gene expression in the rat adrenal cortex.
AB  - It is now known that in the rat there are two distinct species of cytochrome
      P450(11 beta/18), namely aldosterone synthase and 11 beta-hydroxylase. Whereas
      aldosterone synthase is located exclusively in the zona glomerulosa, the zonal
      distribution and site of production of 11 beta-hydroxylase is not entirely clear.
      In the present study we examined the zonal expression of 11 beta-hydroxylase mRNA
      in adrenals from control rats and animals subjected to ACTH treatment and dietary
      sodium restriction using a non-isotopic in-situ hybridization technique. The
      results were compared with those obtained using an inner zone specific antigenic
      (IZAg) marker to give unequivocal identification of the adrenocortical cell
      types. 11 beta-Hydroxylase mRNA was clearly shown to be expressed in the inner
      zones of the control rat adrenal cortex, and none was detected in the zona
      glomerulosa and medulla. The message was more abundant in the outer zona
      fasciculata. A similar pattern of distribution of 11 beta-hydroxylase mRNA was
      observed in adrenals from rats subjected to dietary sodium restriction, although
      the width of the negatively staining layer of zona glomerulosa was significantly
      increased. In rats treated with 100 micrograms ACTH for 1 day, the number of
      cells expressing 11 beta-hydroxylase mRNA was increased, especially in the zona
      reticularis. With continued ACTH treatment, 11 beta-hydroxylase mRNA was found in
      the region of the zona glomerulosa, and after 3 and 5 days of ACTH treatment
      cells expressing 11 beta-hydroxylase mRNA extended to the connective tissue
      capsule. At this time there was a significant reduction in the total expression
      of the message compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308469
TI  - Fragments of chromogranin A are present in the urine of patients with carcinoid
      tumours: development of a specific radioimmunoassay for chromogranin A and its
      fragments.
AB  - Chromogranin A is a well-known protein constituent in granules of neuroendocrine
      cells. It is also known that plasma levels of chromogranin A increase
      considerably in patients with neuroendocrine tumours and thus chromogranin A is
      used as a marker for these tumours. In the present study, we have shown that
      fragments of chromogranin A are excreted into the urine in some patients with
      carcinoid tumours. The chromogranin A molecule appeared in the urine N-terminally
      cleaved at amino acid positions 116 and 210, which are previously reported
      cleavage sites of the molecule. The fragments identified were mainly of about 35
      kDa in size. The unprocessed chromogranin A molecule was not excreted in the
      urine. Five out of 40 patients excreting the fragments had slight tubular
      dysfunction in the kidneys. We also showed that these renally excreted split
      products of chromogranin A were immunogenic and could be used for production of
      antibodies against chromogranin A. These antibodies were used both for
      immunocytochemistry and for the development of a specific and sensitive
      radioimmunoassay for chromogranin A and its fragments. Measurements of plasma
      chromogranin A by radioimmunoassay appeared to be a better marker for tumour
      growth than were measurements of chromogranin A in the urine.

PMID- 8308470
TI  - The inter-relationship between insulin and chromium in hyperinsulinaemic
      euglycaemic clamps in healthy volunteers.
AB  - Evidence in the literature suggests that the trace element chromium may have a
      role in glucose homeostasis through the regulation of insulin action. We have
      previously reported a significant reduction in plasma chromium levels in healthy
      individuals, following a 75 g oral glucose load, and after meals and glucose
      dependent uptake of chromium in insulin-dependent tissues in vitro. However, in
      vivo it is unclear whether the changes in plasma chromium relate to changes in
      plasma glucose or insulin. The present study describes a series of euglycaemic
      hyperinsulinaemic clamps designed to attempt to define the initiator of changes
      in plasma chromium levels in ten healthy individuals. The data showed a
      significant (P < 0.01) reduction in fasting plasma chromium levels following
      glucose infusion and an initial bolus of insulin. Significant (P < 0.02)
      increases in post-clamp urinary chromium excretion were insufficient to explain
      the decrease in plasma levels. During the recovery phase of an extended two-phase
      clamp protocol we found plasma insulin levels decreased by 70% within 10 min,
      associated with an increase in plasma chromium levels of 30% and no significant
      change in plasma glucose level. These data indicate that alterations in plasma
      glucose are unlikely to be directly related to changes in plasma chromium, whilst
      supporting the hypothesis that plasma insulin may influence plasma levels of this
      trace element. In contrast, plasma zinc was unaffected throughout these clamp
      studies.

PMID- 8308471
TI  - Scientific misconduct--does it exist?

PMID- 8308472
TI  - Prevention and management of fraud--in theory.

PMID- 8308473
TI  - Management of research misconduct--in practice.

PMID- 8308474
TI  - Research misconduct: a brief history and a comparison.

PMID- 8308475
TI  - The pathology of research fraud: the history and politics of the US experience.

PMID- 8308476
TI  - Diabetes mellitus in the black communities of southern Africa.

PMID- 8308477
TI  - Can laboratory testing improve screening strategies for deep vein thrombosis at
      an emergency unit?
AB  - OBJECTIVES: To study various markers of blood coagulation and fibrinolysis in
      relation to the extension of deep vein thrombosis (DVT), and to compare the
      diagnostic usefulness of these markers as screening tests for excluding DVT.
      DESIGN: A clinical study of patients admitted to an emergency unit. SETTING:
      Ostra Hospital, Goteborg, Sweden. SUBJECTS: One hundred and five patients with a
      clinical suspicion of DVT. MAIN OUTCOME MEASURES: Phlebography was used as the
      reference method for a diagnosis of DVT. Small distal thromboses as well as large
      proximal thromboses were included. Plasma D-dimer as well as other markers of
      coagulation and fibrinolysis were analysed. RESULTS: Twenty-eight proximal and 20
      distal DVTs were found. Plasma D-dimers (one ELISA and two latex assays), fibrin
      monomer, prothrombin fragment 1 + 2 (F1+2), thrombin-antithrombin III complex
      (TAT) and the t-PA-PAI-1 complex were all significantly correlated to the
      extension of DVT, whilst fibronectin, tissue-type plasminogen activator (t-PA),
      single-chain urokinase-type plasminogen activator (scru-PA) and plasminogen
      activator inhibitor 1 (PAI-1) were not. The sensitivity was 94% for the D-dimer
      ELISA and one of the latex methods (latex-B), at a specificity of 60% and 68%,
      respectively. The negative predictive value was 92% for ELISA and 93% for latex
      B, and both assays showed a negative predictive value of 100% for proximal DVTs.
      Fibrin monomer, F1+2, TAT, D-dimer (latex-S) and the t-PA-PAI-1 complex all
      showed lower negative predictive values (88, 84, 79, 78 and 65% respectively).
      CONCLUSIONS: Sensitivity and negative predictive values for a latex assay (D
      dimer latex-B) was similar to that of a D-dimer ELISA: With a sensitivity of 94%
      (100% for proximal DVTs) such a latex assay may be included in a screening
      strategy for DVT at an emergency unit. However, the safety of such an approach
      has to be tested in other prospective studies.

PMID- 8308479
TI  - Haematocrit, hypertension and risk of stroke.
AB  - OBJECTIVES: To assess the relationship between haematocrit and risk of stroke.
      DESIGN: Prospective study of a cohort of men followed up for 9.5 years. SETTING:
      General practices in 24 towns in England, Scotland and Wales (British Regional
      Heart Study). SUBJECTS: A total of 7735 men aged 40-59 years at screening,
      selected at random from one general practice in each of 24 towns. MAIN OUTCOME
      MEASURES: Fatal and non-fatal strokes. RESULTS: During a follow-up period of 9.5
      years for all men there were 123 stroke events (33 fatal) in the 7346 men in whom
      the haematocrit level had been determined. In the cohort as a whole, risk of
      stroke was significantly raised at haematocrit levels > or = 51% (relative risk
      [RR] = 2.5; 95% confidence intervals [CI] 1.2-5.0) after adjustment for age,
      social class, smoking, body mass index, physical activity, presence of diabetes
      and pre-existing ischaemic heart disease. Further adjustment for systolic blood
      pressure did not attenuate this association (RR = 2.4; 95% CI 1.2-4.9). A raised
      haematocrit was associated with an increase of stroke only in men with
      hypertension (systolic blood pressure > or = 160 mmHg or diastolic blood pressure
      > or = 90 mmHg or on regular antihypertensive treatment). No increased risk of
      stroke was seen at the higher haematocrit level (> or = 51%) in normotensive men.
      At haematocrit levels below 51%, hypertension was associated with a three-fold
      increase in risk of stroke compared with normotension (RR = 3.4, 95% CI 2.3,
      5.1). At haematocrit levels > or = 51%, hypertension was associated with a nine
      fold increase in risk of stroke compared with normotension (RR = 9.3; 95% CI 4.2,
      21.0). Exclusion of men receiving regular antihypertensive therapy did not alter
      the strong associations seen. CONCLUSION: The data suggest that an elevated
      haematocrit is an independent risk factor for stroke and that it interacts
      synergistically with elevated blood pressure.

PMID- 8308478
TI  - Urinary thromboxane A2 metabolites in patients presenting in the emergency room
      with acute chest pain.
AB  - OBJECTIVES: The diagnosis of acute myocardial infarction (MI) is difficult in
      emergency rooms where large groups of patients present with chest pain.
      Confirmation of the diagnosis of MI based on the myocardial band of creatine
      phosphokinase may take a day. A more rapid diagnostic screening procedure is
      desirable and for this reason we evaluated urine thromboxane. DESIGN: The study
      consisted of patients presenting with chest pain. Urine samples were obtained in
      the emergency room and on the following 5 days for those patients who were
      admitted to the hospital. The urine samples were used to determine the levels of
      immunoreactive 11-dehydro-thromboxane B2 (i-11-dehydro-TXB2) and 2,3-dinor
      thromboxane B2 (i-2,3-dinor-TXB2). Myocardial infarction was defined as an
      increase in the myocardial band fraction of plasma creatine phosphokinase (> 5%
      of the total) and changes in the electrocardiogram. The patients' diagnoses were
      retrospectively correlated with thromboxane metabolite levels. SETTING: The
      present study took place in the emergency rooms of two major hospitals:
      Georgetown University Medical Center, Washington DC, and Fairfax Hospital,
      Virginia, USA. SUBJECTS: The study comprised 369 patients presenting with acute
      chest pain and consisted of 247 men and 122 women aged 30-94 years. MAIN OUTCOME
      MEASURES: The outcome measure of this study was the predictive value of i-11
      dehydro TXB2 and i-2,3-dinor-TXB2, for the diagnosis of MI, in patients
      presenting in the emergency room with chest pain. RESULTS: Patients undergoing an
      MI had significantly higher levels of both thromboxane metabolites in their urine
      in the emergency room, when compared to patients undergoing a cardiac event other
      than an MI or to patients with unstable angina. Thromboxane metabolite levels
      rapidly returned to normal on the days following admission to the hospital.
      Aspirin intake appeared to significantly decrease the levels of i-11-dehydro
      TXB2, but not that of i-2,3-dinor-TXB2. CONCLUSIONS: The measurement of
      thromboxane metabolites in the urine may provide a more rapid, accurate and cost
      effective means of diagnosing MIs in patients presenting with chest pain.

PMID- 8308480
TI  - Familial hypercholesterolaemia-like syndrome with apolipoprotein E-7 associated
      with marked Achilles tendon xanthomas and coronary artery disease: a report of
      two cases.
AB  - We observed two patients with hypercholesterolaemia and tendon xanthomas
      associated with apolipoprotein (apoE-7) E-7, a rare variant of the apoE isoforms.
      Both suffered from coronary artery disease and had undergone a coronary bypass
      operation. Their cholesterol levels were 268 and 310 mg dl-1, respectively. Both
      patients had marked xanthomas in the Achilles tendons. Both also suffered from
      diabetes. Although their clinical and laboratory findings were compatible with
      typical familial hypercholesterolaemia (FH), the analysis of low-density
      lipoprotein (LDL) receptors in cultured fibroblasts showed no abnormality of
      binding, internalization or degradation of 125I-LDL. Diabetic control with a low
      calorie, low-fat diet led to the rapid reduction of serum cholesterol. Other
      family members of the patients with apoE-7, who were normoglycaemic, showed
      normal cholesterol levels and no xanthomas. These findings suggest that
      coexistent diabetes mellitus may induce overt hyperlipidaemia and accumulation of
      lipids in tissues in subjects with apoE7.

PMID- 8308481
TI  - Sarcoidosis and agnogenic myeloid metaplasia.
AB  - Agnogenic myeloid metaplasia (AMM) was recognized 3 years after a diagnosis of
      sarcoidosis in a 45-year-old man. This is the second reported instance of that
      association, and the 15th reported case in which systemic granulomata have been
      associated with a myeloproliferative disorder (MPD). In the client population at
      risk, this connection would be expected to occur by chance once in 1700 years.
      Therefore, it is unlikely that the association is fortuitous. Systemic
      granulomata may represent an immunologic response to antigens of neoplastic
      origin in MPD.

PMID- 8308482
TI  - Thymoma with immunodeficiency (Good's syndrome) associated with selective
      cobalamin malabsorption and benign IgM-kappa gammopathy.
AB  - We have described the first case, to our knowledge, in which recurrent
      respiratory tract infections were the primary manifestation of thymoma with
      immunodeficiency (Good's syndrome) associated with cobalamin malabsorption and
      immunoglobulin M-kappa (IgM-kappa) M component. The intrinsic factor receptor
      activity was dramatically decreased in a mucosal homogenate prepared from ileal
      biopsies. This decreased activity could be the principal cause of the
      malabsorption of labelled cobalamin which was observed in the presence of
      intrinsic factor. However, it could be the consequence of the cobalamin
      deficiency, as it is known that a cobalamin deficiency can affect the
      assimilation of cobalamin, even in presence of exogenous intrinsic factor.

PMID- 8308483
TI  - Carcinoma of the pituitary in association with pulmonary stenosis and
      microcephaly.
AB  - We report a 31-year-old female with microcephaly and pulmonary stenosis who
      developed a pituitary carcinoma: this combination of anomalies has not been
      described previously.

PMID- 8308484
TI  - Osteonecrosis of the femoral head in refractory coeliac disease.
AB  - Osteonecrosis has been described occurring in many clinical conditions that
      require steroid administration. Mechanisms by which steroids produce
      osteonecrosis are not well known and the importance of the underlying disease has
      been recently emphasized. We report on a 48-year-old woman with coeliac disease
      who developed osteonecrosis of the femoral head after being treated with steroids
      for non-response to gluten withdrawal. We stress the possible role of
      osteoporosis and osteomalacia, frequently found in patients with coeliac disease,
      in the pathogenesis of this complication, and advise using drugs other than
      steroids in the treatment of refractory coeliac disease.

PMID- 8308485
TI  - Oesophageal ulcers in HIV-infected patients.

PMID- 8308486
TI  - Rhabdomyolysis with acute renal failure due to Borrelia burgdorferi.

PMID- 8308487
TI  - End of the coffee mystery: diterpene alcohols raise serum low-density lipoprotein
      cholesterol and triglyceride levels.

PMID- 8308489
TI  - Distinction between places and paths in rats' spatial representations.
AB  - Rats were trained on a 3-dimensional, 4-arm radial maze. In Experiment 1, Ss
      trained to climb to the single goal platform chose fewer novel routes to the goal
      than Ss trained to climb to the 4 spatially distinct platforms. In Experiment 2 a
      reinforcement contingency was imposed, requiring a novel route choice on each
      trial to receive reinforcement. Learning to associate route choice with
      reinforcement outcome was much more difficult for Ss tested with the single goal
      than for Ss tested with the 4 distinct goals. In Experiment 3 a partitioned
      central platform group learned the reinforcement contingency as quickly as the Ss
      given 4 spatially distinct platforms. In Experiment 4, distinctive floor inserts
      did not affect performance relative to no inserts.

PMID- 8308488
TI  - Scratch and match: pigeons learn matching and oddity with gravel stimuli.
AB  - Two groups of 4 pigeons learned either matching-to-sample or oddity-from-sample
      by digging in white and black gravel for buried grain. Learning occurred as early
      as Trial 11, and acquisition was accelerated by as much as 100-fold compared with
      learning in traditional key-peck environments. Control experiments showed that
      performance was not controlled by cues other than the gravel stimuli and was not
      due to distributed practice effects of 8 trials per day and longer intertrial
      intervals.

PMID- 8308490
TI  - Selective breeding for negative contrast in consummatory behavior.
AB  - Rats showing either large or small reductions in licking following a shift from
      32% to 4% sucrose were selectively bred for 7 generations. Rats from the 2
      resulting lines reliably differed in successive negative contrast and in activity
      (radial-arm maze and open field). Differences in activity and contrast were not
      correlated. Heritability (h2) of the reaction to sucrose shift was reliable in
      the last 6 filial generations and equaled 0.64 in the F7 generation. The 2 lines
      did not differ (a) in response to the absolute rewarding value of sucrose or
      cocaine; (b) in open-field defecations or thigmotaxis; (c) in anticipatory
      contrast; or (d) in responsivity to midazolam. Responsivity to reward reduction
      may involve a relatively delimited psychological process that is amenable to
      selection.

PMID- 8308491
TI  - Quantitative two-process analysis of avoidance conditioning in goldfish.
AB  - The shuttlebox performance of goldfish was studied under standardized conditions
      in a variety of problems--with or without an avoidance contingency, a conditioned
      stimulus (CS)-termination contingency, and an escape contingency. The effects of
      CS-only, unconditioned stimulus (US)-only, and explicitly unpaired training were
      also examined. All the data could be simulated quantitatively with a version of
      O. H. Mowrer's (1947) 2-process theory expressed in 2 learning equations (1
      classical, the other instrumental) and a performance equation. The good fit
      suggests that the theory is worth developing further with new experiments
      designed to challenge it.

PMID- 8308492
TI  - Control of instrumental performance by Pavlovian and instrumental stimuli.
AB  - Two experiments used rats to examine the transfer of control of a stimulus to a
      new instrumental response. That transfer was successful to the degree that the
      stimulus and the response shared a common outcome. The transfer was more
      substantial, however, when the stimulus signaled the availability of that outcome
      for another instrumental response compared with signaling its occurrence in a
      Pavlovian manner. That result suggests that the stimulus-outcome associations
      formed during instrumental training are not reducible to a Pavlovian association.

PMID- 8308493
TI  - Context-specificity of target versus feature inhibition in a feature-negative
      discrimination.
AB  - Four experiments with rats examined the effects of a context switch on inhibition
      that was acquired during a feature-negative discrimination. A target conditioned
      stimulus was paired with food when it was presented alone but occurred without
      food when it was combined with a feature stimulus. A context switch following
      training did not disrupt inhibition conditioned to the feature. However,
      responding to the target was more difficult to inhibit when it was tested in a
      different context. It is suggested that both the target and the feature acquired
      inhibition and that the target's inhibition was especially sensitive to the
      context. The feature may inhibit responding to the target (a) by directly
      suppressing the representation of the food and (b) by activating the target's own
      inhibitory association with food, which is at least partly context-specific.
      Implications for theories of inhibition and negative occasion-setting are
      discussed.

PMID- 8308494
TI  - Kinetics of matching.
AB  - Rats responded on concurrent variable interval schedules of brain stimulation
      reward in 2-trial sessions. Between trials, there was a 16-fold reversal in the
      relative rate of reward. In successive, narrow time windows, the authors compared
      the ratio of the times spent on the 2 levers to the ratio of the rewards
      received. Time-allocation ratios tracked wide, random fluctuations in the reward
      ratio. The adjustment to the midsession reversal in relative rate of reward was
      largely completed within 1 interreward interval on the leaner schedule. Both
      results were unaffected by a 16-fold change in the combined rates of reward. The
      large, rapid, scale-invariant shifts in time-allocation ratios that underlie
      matching behavior imply that the subjective relative rate of reward can be
      determined by a very few of the most recent interreward intervals and that this
      estimate can directly determine the ratio of the expected stay durations.

PMID- 8308495
TI  - Molar function depends on molecular structure of behavior.
AB  - Pigeons chose between green side keys, then waited a shorter or longer time
      before pecking a center key, and finally chose between red side keys. Two
      successive left choices (to green and then red) with a shorter wait intervening,
      or 2 successive right choices with a longer wait intervening, were intermittently
      reinforced with food. The 2 required waiting times and the relative frequency of
      reinforcement for the shorter reinforced pattern were varied. Molar preference,
      defined in terms of coherent responses that satisfied the molecular reinforcement
      contingency, conformed to the highly adaptive matching level, but molar
      preference, defined in terms of incoherent responses, did not. The molar matching
      result therefore generalizes to responses with complex molecular structures
      provided that analyses distinguish between coherent and incoherent responses. The
      results are compatible with the idea that awareness can facilitate adaptation.

PMID- 8308496
TI  - Importance of listening.

PMID- 8308497
TI  - Psychiatric interview.

PMID- 8308498
TI  - Umbilical 'stones'.

PMID- 8308499
TI  - Low-risk pregnancies.

PMID- 8308500
TI  - Acyclovir: how often should it be used?

PMID- 8308501
TI  - Family physicians: exercise testing and community needs.

PMID- 8308502
TI  - Post-myocardial infarction survival: plus ca change ...

PMID- 8308503
TI  - Geographic variation in exercise testing by family physicians.
AB  - BACKGROUND: The purposes of this study were to determine the extent to which
      exercise stress testing is performed by family physicians; whether rural
      physicians are more likely to utilize exercise stress testing than their urban
      counterparts; and what factors influence their decisions. METHODS: A random
      sample of 211 practicing members of the Nebraska Academy of Family Physicians was
      surveyed. Responses were received from 163 (77%). To ensure independence, if two
      or more subjects were members of the same group practice, one was randomly
      assigned to the study, for a total of 125 respondents available for analysis.
      Questionnaire items included performance of exercise stress tests, population
      base, and distance to the nearest specialist who performed the test. Respondents
      were classified as urban, rural, or frontier, based on population per square mile
      in their county. RESULTS: Seventy-three of the 125 respondents (58%) reported
      that they perform exercise stress testing. Physicians in rural or frontier
      counties were twice as likely to perform the test as urban physicians (P < .001).
      Similar results were found for distance to the closest specialist who performs
      exercise stress tests (P < .001) and reported population base (P < .01). Of those
      performing the procedure, 42 (58%) indicated they had learned it during
      residency, whereas 15 (21%) were self-taught or had learned from a colleague.
      CONCLUSIONS: Family physicians in rural Nebraska are significantly more likely to
      perform exercise stress testing than those in urban areas and much more likely to
      do stress testing than previous national studies indicate. National guidelines
      should acknowledge the need for family physicians to perform exercise tests and
      promote training in this procedure.

PMID- 8308504
TI  - Discriminant value of symptoms in patients with dyspepsia.
AB  - BACKGROUND: Family physicians encounter many pitfalls in managing and treating
      dyspeptic patients, most of whom are treated in family practice based solely on
      their signs and symptoms. METHODS: A computer literature search followed by a
      systematic methodological appraisal was performed to identify studies that
      evaluated clinical symptomatology in dyspeptic patients. RESULTS: Ten studies,
      none of which took place in a family practice, fulfilled our inclusion criteria.
      The main conclusion drawn from outpatient populations and patients referred for
      open-access endoscopy was that certain clusters of symptoms have a negative
      predictive value for organic causes of dyspepsia. Higher age, male sex, pain at
      night, relief by antacids or food, and previous history of peptic ulcer disease
      were identified as predictors of organic causes for abdominal symptoms.
      CONCLUSIONS: These findings can be helpful to family physicians in determining
      the need for endoscopy referral. However, since the diagnostic values of tests in
      family practice may differ from those in referred populations, there is a need
      for prospective studies in primary care.

PMID- 8308505
TI  - Fluticasone propionate: an effective alternative treatment for seasonal allergic
      rhinitis in adults and adolescents.
AB  - BACKGROUND: Topical corticosteroids are widely regarded as the reference standard
      in allergic rhinitis therapy because they are well tolerated and effective
      against all rhinitis symptoms. We evaluated the efficacy, onset of action, and
      safety of two dosing regimens of the new corticosteroid fluticasone propionate
      compared with that of beclomethasone dipropionate in patients with moderate to
      severe seasonal allergic rhinitis. METHODS: In this double-blind, randomized
      multicenter trial, 110 adolescents and 128 adults were treated for 4 weeks with
      one of the following regimens: fluticasone aqueous nasal spray 100 micrograms
      twice daily or 200 micrograms once daily, beclomethasone aqueous nasal spray 168
      micrograms twice daily, or placebo. RESULTS: Patient-rated scores for nasal
      obstruction, rhinorrhea, and combined nasal symptoms indicated that the two
      fluticasone regimens were equally effective and that both were superior to
      beclomethasone during most of the study (P < or = .05) and to placebo throughout
      the study (P < or = .01). Both fluticasone regimens also demonstrated significant
      clinical efficacy by 24 hours after the first dose. Clinician-rated mean total
      nasal symptoms scores for all three active treatments were superior to placebo at
      most time points but were not significantly different from each other. All
      treatments were well tolerated, with similar incidence and type of adverse events
      in all treatment groups and no apparent effects on hypothalamic-pituitary-adrenal
      (HPA) axis function. CONCLUSIONS: Fluticasone aqueous nasal spray was effective
      in relieving nasal symptoms in adolescents and adults with seasonal allergic
      rhinitis. Fluticasone administered once or twice daily was superior to
      beclomethasone administered twice daily in relieving nasal obstruction and
      rhinorrhea and in reducing nasal symptoms more quickly.

PMID- 8308506
TI  - Lethal tissue temperature during cervical cryotherapy with a small flat
      cryoprobe.
AB  - BACKGROUND: Some female patients, especially those with cervical intraepithelial
      neoplasia III (CIN III), are not successfully cured following cervical
      cryotherapy, for which a small flat cryoprobe tip is commonly used. The
      thermodynamic effect produced in the cervical tissue by this device has not been
      previously described. This study examined the capability of a small flat
      cryoprobe tip to generate a lethal temperature during thermocouple-monitored
      cryosurgery of the cervix. METHODS: A thermocouple was placed in the cervix 5 mm
      from the cryoprobe margin, and a pyrometer indicated temperatures generated by
      nitrous oxide cryosurgery. Iceball lateral spread of freeze was measured with a
      cryosurgical iceball gauge. RESULTS: A minimum temperature of -2C degrees was
      generated at the termination of freeze (6 1/2 minutes). The maximum lateral
      spread of freeze at termination was 6.2 mm. A lethal zone of 4.2 mm was estimated
      based on a 2-mm recovery zone. CONCLUSIONS: When compared with morphometric
      studies of cervical dysplasia depth of involvement, an estimated 12.5% of CIN III
      would be inadequately treated based on our in vivo data. A small flat cryoprobe
      is incapable of eradicating all severe premalignant cervical disease deep within
      the glandular clefts. An alternative treatment method, such as electrosurgical
      loop excision of the cervical transformation zone (ELECTZ), therefore, may be the
      preferred treatment modality for CIN III:

PMID- 8308507
TI  - Physicians' perceptions of the impact of the reclassification of vaginal
      antifungal agents.
AB  - BACKGROUND: In January 1991, miconazole and clotrimazole were released as
      nonprescription therapy for vaginal candidiasis. Considering the number of women
      suffering from vaginal symptoms annually, these new over-the-counter (OTC)
      products may have a considerable impact on women's health care. METHODS: All 191
      family physicians and obstetrician and gynecologist members of the Toledo and
      Lucas County Academy of Medicine were surveyed in June 1992. The survey
      instrument was constructed to include questions regarding physician perceptions
      of the impact of OTC antifungal agents on preventive care; the type of advice
      they currently give patients concerning the use of OTC antifungal agents; and
      their estimates of the incidence of misdiagnosis and reported side effects
      resulting from use of OTC antifungal agents. RESULTS: Of the surveyed physicians,
      24% concluded that the reclassification of antifungal agents was a positive
      change for their female patients, 19% believed it was a negative change, and the
      remaining 57% noted no impact on their patients' well-being. Over 40% of the
      physicians indicated that four to six of their patients had delayed treatment for
      other vaginal conditions because of inappropriate use of an OTC antifungal
      preparation within the last year. On a positive note, the physicians in favor of
      the OTC preparations believed their patients were getting faster and more
      economical care and were in "control of their health care." CONCLUSIONS:
      Physicians participating in this study reported mixed opinions concerning the
      reclassification of vaginal antifungal agents and raised several pertinent
      questions that require further examination.

PMID- 8308508
TI  - Asthma in ambulatory care: use of objective diagnostic criteria.
AB  - Asthma, a disease of reversible airway hyperactivity, is responsible for 6.5
      million visits to ambulatory care offices each year. In spite of treatment
      advances, asthma-related deaths have increased 31% from 1980 to 1987. The
      severity of asthma is often determined solely by history and physical
      examination, which can result in either overestimation or underestimation of
      disease severity. To optimize management, objective quantitative criteria should
      be added to the diagnostic evaluation. The use of peak flow meters provides
      physicians with easily obtainable objective measurements to augment their
      diagnostic armamentarium in the treatment of asthma.

PMID- 8308509
TI  - Competing demands of primary care: a model for the delivery of clinical
      preventive services.
AB  - Despite a high level of support for the importance of clinical prevention,
      physician delivery of preventive services falls well below recommended levels.
      Competing demands faced by physicians during the medical encounter present a
      major barrier to the provision of specific preventive services to patients. These
      demands include acute care, patient requests, chronic illnesses, psychosocial
      problems, screening for asymptomatic disease, counseling for behavior change,
      other preventive services, and administration and management of care. This paper
      outlines how competing demands affect physician delivery of clinical preventive
      services and provides a model designed to help practicing physicians improve the
      delivery of preventive services. This model can be helpful in the planning of
      preventive interventions in primary care settings and can facilitate a better
      understanding of physician behavior.

PMID- 8308510
TI  - Penicillin failure and copathogenicity in streptococcal pharyngotonsillitis.
AB  - Recurrent group A beta-hemolytic streptococcus (GABHS) pharyngotonsillitis
      related to penicillin failure presents a serious clinical problem. Failure to
      eradicate streptococci from patients can occasionally lead to rheumatic fever and
      rarely to glomerulonephritis. beta-lactamase-producing strains of aerobic and
      anaerobic bacteria in inflamed tonsils have been associated with increased
      failure rates of penicillins in the eradication of these infections. These
      organisms include Staphylococcus aureus, Haemophilus influenzae and H
      parainfluenzae, Moraxella catarrhalis, Fusobacterium sp, and pigmented Prevotella
      and Porphyromonas spp. The indirect pathogenicity of these organisms is apparent
      in their ability not only to survive penicillin therapy but also to protect
      penicillin-susceptible pathogens from that drug. These organisms have
      demonstrated the ability to protect GABHS in vitro and in vivo from penicillin.
      Numerous reports have described the successful therapy of recurrent GABHS
      tonsillitis with antimicrobials directed at both GABHS and the beta-lactamase
      producing organisms.

PMID- 8308511
TI  - Uses and safety of acyclovir in pregnancy.
AB  - Acyclovir, an antiviral nucleoside analogue, is a widely used agent highly
      specific for herpes simplex and varicella-zoster viruses. Unintended exposure to
      acyclovir early in pregnancy, which is not uncommon, may cause excessive maternal
      and physician anxiety. This drug has not been studied prospectively in large
      numbers of pregnant women and lacks the Food and Drug Administration's approval
      for gestational use unless benefits clearly outweigh potential fetal harm.
      However, data published since acyclovir became available do not indicate
      increased adverse effects related to its use in pregnancy, especially if
      prescribed in selected situations, such as disseminated primary herpes simplex
      infections or maternal varicella pneumonia. This article reports the impact of
      inadvertent acyclovir exposure on a woman during the first trimester of pregnancy
      and reviews the literature on acyclovir's pharmacology, safety profile, and
      potential uses during pregnancy.

PMID- 8308512
TI  - Ethics and health care reform.

PMID- 8308513
TI  - Zits for health.

PMID- 8308514
TI  - Detection of small and large genomes of hepatitis D virus in serum of patients
      with hepatitis D.
AB  - By combining the polymerase chain reaction (PCR) with restriction enzyme
      digestion technologies, we characterized the genomes for the small and large
      delta proteins of HDV in retrospective analysis of sera from 10 patients with
      varied clinical outcomes. Both small and large genomes of HDV were present in all
      13 serum samples from the 6 acute and 4 chronic cases studied, while the specific
      HDV proteins (P24 and P27) could be detected by immunoblot analysis in only 4 of
      them. The relative amounts and ratios of the genomes for the large and the small
      proteins of HDV were different for each individual. The molecular ratio of large
      to small HDV genomes in serum correlated with viral replication. When the
      replication of HDV RNA increased, the ratio decreased and vice-versa. No specific
      correlation, however, was found between the ratio of both molecular forms and the
      clinical outcome.

PMID- 8308515
TI  - Genome type analysis of Chilean adenovirus strains isolated in a children's
      hospital between 1988 and 1990.
AB  - In a study designed to evaluate the genetic variability of adenovirus strains
      associated with infantile cases of respiratory disease requiring hospitalization,
      a collection of 136 adenovirus isolates obtained in the Roberto del Rio
      Children's Hospital of Santiago, Chile between June 1988 and November 1990 was
      studied by restriction enzyme analysis. Nasopharyngeal aspirates were obtained on
      admission from children under 2 years. During the study period a total of 227
      adenovirus respiratory infections (ARI) were diagnosed at the ward for ARI by
      immunofluorescence, representing 23% of all admissions. Fifty percent of the 136
      typed strains were found to belong to subgenus B, and the other 50% corresponded
      to subgenus C. Digestion with a set of seven enzymes allowed the identification
      of nine different genome types of subgenus C, three of which had not been
      previously described, exhibiting novel restriction patterns with either BgI II or
      BstEII. Ad7h, identified in 66 isolates, was the predominant genome type and was
      associated with the nine cases requiring mechanical respiratory assistance and
      with the two fatalities recorded during the 29 months. No differences were found
      between the age and sex distribution of subgenus B and C genomic variants, but
      the mean length of hospital stay (X +/- 2 SE) recorded among patients infected
      with subgenus B types was significantly higher (17.72 + 4.52 days (n = 55) vs.
      7.54 + 1.70 days (n = 53); F = 17.22; P < 0.0001).

PMID- 8308516
TI  - Rapid detection of hepatitis C virus RNA by direct capture from blood.
AB  - A new diagnostic assay for hepatitis C virus RNA detection is described. HCV
      genomic RNA is captured onto streptavidin-coated magnetic beads by solution
      hybridization with biotinylated complementary oligonucleotides. The specificity
      of the capture assay is confirmed using different capture oligonucleotides as
      well as sera representing different types of HCV. Sensitivity was determined by
      testing serial dilutions of a HCV infected plasma. A panel of 50 sera was tested
      for anti-HCV by a Line Immunoassay and for HCV-RNA by both a conventional
      guanidinium extraction method and the new capture assay. The specificity of the
      capture assay was 95.8% and the sensitivity was 92.3% compared to the standard
      protocol. This method provides a rapid and simple alternative for HCV-RNA
      detection in blood samples.

PMID- 8308517
TI  - Cytomegalovirus/herpesvirus and carotid atherosclerosis: the ARIC Study.
AB  - Ubiquitous viruses such as members of the human herpes virus group, particularly
      cytomegalovirus (CMV), have been proposed to be clinically important agents in
      the initiation and progression of atherosclerosis. Antibodies to CMV and herpes
      simplex virus type 1 (HSV1) and type 2 (HSV2) were determined in 340 matched case
      control pairs from the Atherosclerosis Risk in Communities (ARIC) Study. Cases
      were defined by B-mode ultrasonography as persons with thickened carotid artery
      walls consistent with early atherosclerosis but without a history of
      cardiovascular disease. Controls were defined as persons without thickened walls
      or history of cardiovascular disease. The case-control odds ratio for CMV
      antibodies was 1.55 (P = .03), for HSV 1.41 (P = .07), and for HSV2 0.91 (P =
      .63). When adjustment was made for potential confounders, the odds ratios were
      1.36 for CMV (P = .24), 1.21 for HSV1 (P = .45), and 0.61 (P = .05) for HSV2.
      These results suggest a modest association between CMV and asymptomatic carotid
      wall thickening consistent with early atherosclerosis.

PMID- 8308518
TI  - Blood in saliva of patients with acquired immunodeficiency syndrome: possible
      implication in sexual transmission of the disease.
AB  - The presence and concentration of haemoglobin in saliva of anti-human
      immunodeficiency virus (HIV) positive subjects, anti-HIV-negative subjects at
      high risk of infection, and healthy controls were studied. One hundred eighty
      eight subjects were anti-HIV-positive intravenous drug abusers (IVDA), 22 were
      anti-HIV-positive homosexual men, 23 were anti-HIV-positive heterosexual
      contacts, 132 were anti-HIV-negative IVDA, 35 were anti-HIV-negative homosexual
      men, and 154 were healthy controls. Two milliliters of saliva was collected in
      the morning before brushing teeth, and the presence and the concentration of
      haemoglobin were determined. Based on hemoglobin, the data show that the anti-HIV
      positive IVDA have the highest tendency to bleeding. The difference between this
      group with respect to anti-HIV-negative IVDA (P < 0.05) and compared with healthy
      controls (P < 0.01) is statistically significant. This is also true of anti-HIV
      positive heterosexual contacts with respect to healthy controls (P < 0.01). Our
      data show that all at-risk groups, both anti-HIV positive and anti-HIV negative,
      have higher haemoglobin concentration than the control group; this difference
      reaches statistical significance only between anti-HIV-positive IVDA and controls
      (P < 0.01). The concentration of haemoglobin is significantly higher in subjects
      with CD4+ lymphocytes < 200/mm3 compared to subjects with CD4+ lymphocytes >
      200/mm3 (P < 0.01), in subjects with AIDS-related complex (ARC)/AIDS compared to
      asymptomatic/PGL subjects (P < 0.01), and in subjects with stomatitis compared to
      subjects without stomatitis (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308519
TI  - High titers of anti-Epstein-Barr virus DNA polymerase are found in patients with
      severe fatiguing illness.
AB  - Forty-one patients with chronic fatigue syndrome (CFS), 76 healthy controls
      matched with the patient group for age range, sex, race, and socioeconomic class,
      and 22 symptomatic patients with seasonal affective disorder (SAD) had serum
      sampled for antibodies against 2 Epstein-Barr virus (EBV) replicating enzymes.
      Abnormal titers of antibodies were found twice as often in CFS patients as
      controls (34.1% vs. 17.1%), with SAD patients having an intermediate frequency
      (27.3%). Stratifying for disease severity sharpened the differences considerably,
      with the sicker CFS and SAD patients having 52% and 50% abnormal tests,
      respectively; more mildly afflicted CFS and SAD patients had a frequency of
      abnormal tests in the normal range. Antibodies to EBV DNA polymerase (DNAP) were
      the more sensitive of the two tests in that they were positive in all cases but
      one. These findings suggest that antibodies against EBV DNAP may be a useful
      marker in delineating a subset of patients with severe fatiguing illness for
      appropriate treatment trials and for monitoring their outcomes.

PMID- 8308520
TI  - Investigation of varicella-zoster virus DNA by the polymerase chain reaction in
      healthy children with varicella vaccination.
AB  - Investigation of varicella-zoster virus (VZV) DNA in 20 healthy children with
      varicella vaccination was carried out by using the polymerase chain reaction
      (PCR) and nested double PCR. Samples of peripheral blood mononuclear cells (PBMC)
      and throat swabs were simultaneously collected 3 times (before, 1 week, and 4
      weeks after vaccination) for PCR analysis. One sample of PBMC was also obtained
      from each of the 12 healthy children with varicella during the acute phase as a
      positive control. VZV DNA was not found by the first PCR in any samples except
      one PBMC of a control subject. The nested double PCR, which is a more sensitive
      method for VZV DNA detection, was applied to the same samples. The viral DNA was
      detected in every PBMC of the controls, and in 2 (16.7%) PBMC at 1 week and in 6
      (50%) PBMC at 4 weeks after vaccination in the 12 vaccinees with seroconversion.
      In 3 of 4 vaccinees who were seropositive before vaccination, VZV DNA was
      detected in PBMC at 1 or 4 weeks after vaccination. The three vaccinees showed a
      booster immunization with a significant increase in antibody titers. In contrast,
      no VZV DNA could be detected in any throat swabs of all the vaccinees nor in PBMC
      of the vaccinees who did not seroconvert.

PMID- 8308522
TI  - Completely or nearly identical hepatitis B virus strains replicate between
      patients with acute or fulminant hepatitis B and their respective infectious
      sources.
AB  - Five patients with acute hepatitis B and four with fulminant hepatitis B were
      selected for sequencing of the precore/core gene of the virus strains.
      Furthermore, identical sequencing was done with the HBV of the infectious
      sources, i.e., the sexual partner in eight cases and a natural child (chronic
      carrier) infecting the mother in one case. Of the subjects responsible for the
      infection, four were healthy HBV carriers, three suffered from chronic hepatitis
      B, and one from acute and one from fulminant hepatitis B. The nucleotide
      sequences of HBV from both the patients and the implicated sources of infection
      exhibited perfect identity of the precore region and perfect or high identity of
      the core region. The completely or nearly identical strain of virus seemed to
      proliferate successively in the patients following the transmission from the
      infecting individuals regardless of sequence variations and infectious status. In
      two cases a peculiar pattern of infection and disease was found: In one married
      couple the husband, during the incubation period of acute hepatitis B, infected
      his wife, who developed fulminant hepatitis. In another married couple, both
      partners ultimately developed fulminant hepatitis (the wife being the source of
      the infection).

PMID- 8308521
TI  - Antibody response to a synthetic peptide derived from the human papillomavirus
      type 6/11 L2 protein in recurrent respiratory papillomatosis: correlation between
      Southern blot hybridization, polymerase chain reaction, and serology.
AB  - Recurrent respiratory papillomatosis (RRP) is the most common benign tumour of
      the larynx, affecting both children and adults. We present a series of 25
      patients, including 10 cases of juvenile multiple, 8 cases of adult solitary, and
      7 cases of adult multiple RRP. Biopsy tissue from each patient was screened by
      Southern blot hybridization and polymerase chain reaction for the presence of
      human papillomavirus (HPV) DNA. Sera from patients and age- and sex-matched
      controls were tested for the presence of HPV-specific antibodies using a
      synthetic peptide derived from the minor capsid protein (L2) of HPV 6/11. By
      Southern blot hybridization and/or polymerase chain reaction, biopsies from all
      patients were positive for HPV 6/11 DNA. There was no difference in antibody
      response between cases and controls. Female cases and controls had significantly
      higher antibody titers than male subjects. A correlation was observed between the
      HPV-specific antibody level and the number of surgery-necessitating recurrences.

PMID- 8308523
TI  - Variant of hepatitis B virus isolated in Zimbabwe.
AB  - The polymerase chain reaction (PCR) was used to amplify an approximately 1.2 kb
      DNA fragment encompassing the pre-S/S gene region of HBV DNA from serum of
      patients with acute hepatitis B virus infection. Nucleotide sequence analysis
      revealed a number of interesting features in the S gene region. Two Bam HI sites
      were located at nucleotide positions 557 and 872, respectively, in the S gene.
      Guanine (G) was found at nucleotide position 903 as part of AGA, the codon for
      arginine (R) corresponding to amino acid position 122 of the S protein. Adenine
      (A) was found at nucleotide position 1017 as part of AAA, the codon for lysine
      (K) corresponding to amino acid position 160 of the S protein. Nucleotide
      sequence alignment revealed a 97% homology to the corresponding domain of an
      HBVadw genome (clone pFDW294). Within the second loop of the "a" determinant, two
      mutations resulting in substitution of serine or threonine with the hydrophobic
      amino acids, methionine at position 143 and with alanine in place of glycine at
      position 145, are predicted from the consensus nucleotide sequence of the PCR
      derived clones. Subtyping with monoclonal antibodies showed that the HBsAg was of
      the ayw subtype.

PMID- 8308524
TI  - Consistent selection of mutations in the 5'-untranslated region of oral
      poliovirus vaccine upon passaging in vitro.
AB  - We have previously found that upon passaging type 3 oral poliovirus vaccine (OPV)
      in cell cultures the proportion of revertants at nucleotide 472 rapidly increases
      [Chumakov et al.: Proceedings of the National Academy of Sciences of the United
      States of America 88:199-203 1991]. Systematic study on the accumulation of these
      revertants showed that it was dependent on the multiplicity of infection and the
      temperature at which virus was grown. Revertants at position 472 of type 3 OPV
      accumulated faster in vaccines derived from Sabin Original (SO) substrain than
      from RNA-plaque purified (RSO) substrain. The rate of accumulation of 472-C
      revertants differed among cell lines and was higher in overgrown cell cultures
      suggesting that host factors are involved in the selection of mutants. We also
      found that accumulation of mutants occurred in vitro at position 480 in type 1
      and position 481 in type 2 OPV, making the selection for revertants in domain F
      of the 5'-noncoding region a general phenomenon for all three Sabin strains.
      Assessment of the abundance of these mutants may be used for evaluation of the
      quality of OPV lots.

PMID- 8308525
TI  - Factors associated with viremia and elevated transaminase levels in asymptomatic
      hepatitis D virus-infected risk groups.
AB  - To detect hepatitis D virus (HDV) RNA in asymptomatic HDV-infected risk groups,
      Northern blot hybridization was carried out using a strand-specific riboprobe.
      Univariate and multivariate analyses were carried out to evaluate factors
      associated with HDV viremia and elevated transaminase levels in these subjects.
      Two (15%) of 13 antibody to HDV (anti-HDV) -positive intravenous drug addicts, 15
      (33%) of 45 anti-HDV positive prostitutes, and 6 (40%) of 15 anti-HDV positive
      brothel goers had detectable serum HDV RNA. Older age (> 31 years old) was
      negatively associated with HDV RNA (P < .04), while hepatitis B e antigen (HBeAg)
      was positively associated with it (P < .002) in univariate analysis. Only HBeAg
      was still significant in multivariate analysis (P < .05). Of the 76 asymptomatic
      anti-HDV positive case, 28 (37%) had mildly elevated serum ALT levels and only 5
      (7%) had ALT levels more than twice normal (> 80 U/L). HBeAg (P < .05) and HDV
      RNA (P < .02) were two factors associated with ALT elevation in univariate
      analysis, and HDV RNA was the only significant factor in multivariate analysis (P
      < .005). In summary, active replication of HBV seemed to be of help for the
      assembly of HDV and viremia. However, active replication of HDV was associated
      mostly with mildly elevated ALT levels in these subjects. These cases may
      represent a particular group in the disease spectrum of HDV infection.

PMID- 8308526
TI  - Serological response to rotavirus infection in newborn infants.
AB  - We report the identification of rotavirus in stools of newborn infants at the
      "Hospital Materno Infantil de Caricuao" (HMIC) as well as the infants'
      serological responses to various rotavirus strains. The serological responses of
      another group of rotavirus-positive neonates studied previously at the
      "Maternidad Concepcion Palacios" (MCP) hospital was also evaluated. Fifty-four of
      266 (20%) newborns examined at HMIC shed rotavirus. The infection rate was higher
      among infants admitted to the nursery (75%) than in those "rooming in" with their
      mothers (7%) (P < .01). Eleven of the 54 neonates (20%) had diarrhea; seven of
      them experienced mild, short-lived episodes, whereas five had frequent diarrhea
      bouts or diarrhea lasting for over 3 days; the remaining 43 infants were
      asymptomatic. Twenty-seven of 28 rotavirus specimens tested at HMIC had VP7
      serotype 4 specificity and one belonged to VP7 serotype 1; VP4 typing performed
      on 24 of the viruses by RNA hybridization showed these viruses to be similar to
      the M37 strain, a rotavirus previously associated with asymptomatic infections in
      newborns at MCP. IgA seroresponses were detected in eight of 11 infants born at
      HMIC (73%), but most failed to developed neutralization responses to homologous
      or heterologous strains. Newborn infants who had shed the M37 rotavirus strain at
      MCP reacted similarly: 16 of 24 (67%) developed a rotavirus IgA rise, but only
      29% developed a neutralization response.

PMID- 8308527
TI  - Social competence deficits in adolescents at risk for schizophrenia.
AB  - Social competence in subjects at risk for schizophrenia and affective disorder
      and in normal-comparison subjects was examined in childhood and adolescence.
      Based on interviews with the parents of the subjects and with the children and
      adolescents themselves, subjects at risk for schizophrenia had poorer overall
      social competence than subjects at risk for affective disorder and comparison
      subjects in early adolescence and adolescence but not in childhood. In analyses
      of specific aspects of social competence, the adolescents at risk for
      schizophrenia had significantly poorer peer relationships and decreased
      hobbies/interests than the adolescents at risk for affective disorder and the
      normal-comparison adolescents. With respect to school adjustment, however, the
      two groups of adolescent offspring of parents with psychiatric disorders had
      significantly poorer adjustment than the comparison adolescents but did not
      differ from each other on this measure. These results suggest that various
      aspects of poor social competence may precede the onset of schizophrenia and play
      an important role in its development.

PMID- 8308528
TI  - Relationship of positive and negative symptoms to cocaine abuse in schizophrenia.
AB  - The prevalence of cocaine abuse by patients with schizophrenia has led
      researchers to investigate features of the disorder correlated with abuse.
      Although abuse has been found to be more common among patients with a diagnosis
      of paranoid subtype and a history of earlier and more frequent hospitalizations,
      it is unclear if it is related to any particular pattern of negative or positive
      symptoms. This study examines the severity of positive and negative symptoms for
      patients with and without histories of cocaine abuse. Subjects with a history of
      at least 2 months of cocaine abuse (N = 25), no lifetime substance abuse (N =
      20), and 2 months of alcohol abuse with no other substance abuse (N = 23) are
      compared on five-factor analytically and three rationally derived scores from the
      Positive and Negative Syndrome Scale (PANSS). Following a multivariate analyses
      of variance (p < .01), univariate analyses indicated significant differences on
      the negative syndrome scales, with cocaine-abusing subjects exhibiting less
      severe negative symptoms than subjects with no substance-abuse history. Cocaine
      abusing subjects were also found to have been younger at time of first
      psychiatric hospitalization and more likely to qualify for a diagnosis of the
      paranoid subtype.

PMID- 8308529
TI  - Vitamin E in the treatment of tardive dyskinesia: a replication study.

PMID- 8308530
TI  - Schizophrenic inpatients and the chemical war threat.

PMID- 8308531
TI  - Poison ivy dermatitis and secondary mania.

PMID- 8308532
TI  - Psychiatric manifestations of hereditary coproporphyria in a child.

PMID- 8308533
TI  - Nonphysiological (functional) unilateral motor and sensory syndromes involve the
      left more often than the right body.

PMID- 8308534
TI  - Panic disorder, palpitations, and the awareness of cardiac activity.
AB  - One hundred forty-five consecutive patients referred for ambulatory
      electrocardiographic monitoring for the evaluation of palpitations were studied
      just before monitoring. They were compared with 75 asymptomatic, nonpatient
      volunteers. The research battery included a structured diagnostic interview, self
      report questionnaires, and perceptual tasks measuring awareness of cardiac
      activity. After monitoring, symptom reports were compared with concurrent
      electrocardiographic recordings to determine their accuracy. Forty palpitation
      patients (27.6%) had DSM-III-R lifetime panic disorder, and 27 (18.6%) had
      current (1-month) panic disorder. Panic patients were significantly more likely
      to describe their palpitations as "racing" or "pounding" and to have been
      awakened from sleep by them. They did not have more cardiac arrhythmias during 24
      hour, electrocardiographic monitoring, and their symptom reports were
      significantly less likely to be due to demonstrable cardiac irregularities. They
      were not more accurately aware of resting heartbeat than nonpanic palpitation
      patients. They did score higher on self-report measures of somatization,
      hypochondriasis, and bodily amplification.

PMID- 8308535
TI  - Panic, agoraphobia, and panic disorder with agoraphobia. Data from a multicenter
      anxiety disorders study.
AB  - In a cross-sectional investigation of the properties of DSM-III-R panic disorder
      (PD), panic disorder with agoraphobia (PDA), and agoraphobia without history of
      panic disorder (AWOPD), we analyzed demographic, descriptive, comorbidity,
      treatment, and course data for 562 subjects with PD, PDA, or AWOPD in a
      multicenter anxiety-disorders study. In general, AWOPD subjects had the worst
      functioning and PD subjects the best, as measured by length of intake episodes,
      education attained, likelihood of receiving financial assistance, depressive
      comorbidity, and likelihood of having experienced 8 weeks symptom-free. Panic
      disorder with agoraphobia was the most common disorder and emerged as a condition
      intermediate in severity between the other two. Treatments received varied little
      by diagnosis. Most subjects received medication, usually benzodiazepines.
      Psychodynamic psychotherapy was the most frequently received psychosocial
      treatment; cognitive and behavioral approaches were less common. Subjects
      classified with AWOPD were the most likely to have received exposure therapies.

PMID- 8308536
TI  - The frequency and severity of generalized anxiety disorder symptoms. Toward a
      less cumbersome conceptualization.
AB  - The frequency and severity of the symptoms of generalized anxiety disorder (GAD)
      were determined in a sample of 49 patients with the DSM-III-R diagnosis of GAD.
      The frequency of the symptoms was considered to meet the DSM-III-R requirement of
      "often" if the symptoms were present for at least 3 days in every week over a 6
      month period. The severity of the symptoms was rated on a 5-point scale. Seven
      symptoms, all of which belong to the clusters of motor tension and vigilance and
      scanning, were identified as both frequent and at least moderate in terms of
      their intensity. They were provisionally designated as the "criterion symptoms"
      of GAD, in contrast to the symptoms of autonomic hyperactivity, which were found
      to be less frequent and, especially, less intense. A more simplified
      conceptualization of GAD was proposed on the basis of these findings.

PMID- 8308537
TI  - Chronic posttraumatic stress disorder in Vietnamese refugees. A prospective
      community study of prevalence, course, psychopathology, and stressors.
AB  - A community cohort of 145 Vietnamese boat refugees in Norway was prospectively
      studied for presence of chronic posttraumatic stress disorder (PTSD) after
      resettlement. Ten percent had PTSD on arrival and/or after 3 years. This group
      had been exposed to significantly more traumatic stress before their escape
      (e.g., reeducation camps, combat, and other war incidents) and had more
      psychopathology (SCL-90-R Global Assessment Scale) after resettlement. A logistic
      regression analysis indicated that different types of traumatic stress had an
      independent relationship with chronic PTSD. Nine SCL-90-R items discriminated
      between the PTSD group and the rest both on arrival and follow-up. These were not
      anxiety items, but related to interpersonal sensitivity, somatization, and
      aggression. The inclusion of additional diagnostic features in the criteria for
      chronic PTSD is indicated.

PMID- 8308538
TI  - Assessment of independent living skills for psychotic patients. Further validity
      and reliability.
AB  - It is well known that psychotic patients have severe social and life-skill
      deficits. Psychiatric rehabilitation programs are designed to teach these skills
      to patients. Before implementing such a program, patient deficits should be
      evaluated with reliable measures. The present study assessed the psychometric
      properties of the French version of the "Independent Living Skills Survey" (ILSS)
      developed by Wallace, Kochanowicz and Wallace (Wallace C J, Kochanowicz N,
      Wallace J [1985] Independent living skills survey. Unpublished manuscript, Mental
      Health Clinical Research Center for the Study of Schizophrenia, West Los Angeles
      Veterans Administration Medical Center, Rehabilitation Medicine Service
      [Brentwood Division], Los Angeles, CA). Although widely used, the patient version
      of this scale has unknown psychometric properties. The ILSS was composed of 75
      items, rated as present or absent and distributed in 10 scales. The French
      version was administered to 145 patients with a psychotic diagnosis who were
      living in the community. All scales had very good psychometric qualities with the
      exception of the job-maintenance scale. The test-retest reliability varied from
      .48 to .85, and alpha coefficients were good for seven of the nine scales.
      Various aspects of construct validity were explored. The scales discriminated
      between patients as a function of their subgroups, sex, and diagnosis. Concurrent
      validity confirmed the specificity of the ILSS dimensions. Factor analysis
      revealed two factors, one for basic skills and one representing higher order
      skills. Recommendations for future development of the ILSS are proposed.

PMID- 8308539
TI  - Affective reactivity of language in schizophrenia.
AB  - Thirty acutely schizophrenic inpatients each provided two speech samples: one on
      affectively negative, "high-stress" topics and one on affectively positive, "low
      stress" topics. We analyzed these using two different, established methods for
      assessment of deviance in natural language, including clinical measures of
      thought disorder and linguistic measures of reference performance. For the group
      as a whole, the speech on negative topics contained more disorder than did the
      speech on positive topics, as rated both clinically and linguistically, and these
      differences were sizeable and highly significant. Level of language disturbance
      and degree of affective reactivity of language symptoms correlated positively
      with severity of the positive syndrome but were not associated in either
      direction with negative syndrome severity. Affective reactivity of symptoms is
      discussed as a variable potentially relevant to studies of psychophysiology and
      subtyping in schizophrenia.

PMID- 8308540
TI  - Evaluation of three-dimensional MRI exploration of prolactin-secreting
      microadenomas.
AB  - Over an 8-month period (July 1990-to February 1991), we explored 21 women
      presenting with a clinical and laboratory profile of prolactin-secreting
      microadenoma of the pituitary gland. Magnetic resonance imaging (MRI) is
      undoubtedly the most efficient method to explore microadenomas, especially when
      carried out in the absence of any treatment. In 8 cases, MRI was performed in the
      absence of medical treatment and gave a positive result, i.e. always showed a
      focal lesion. In the remaining 13 cases the patients had been treated before the
      exploration, and MRI detected a microadenoma in only 4 cases. The duration of
      treatment and the time elapsed between its withdrawal and the MRI examination did
      not seem to influence the positivity or negativity of the imaging results. Among
      the 9 cases where MRI failed to show a focal lesion, the image was normal in 3
      cases and displayed an arachnoidocele in 3 cases; the pituitary gland was convex
      and homogeneous in 1 case and convex and heterogenous in 3 cases, which raised
      the problem of the effects of bromocriptine on the MRI images. As regards
      signals, in 5 cases the microadenoma was hyperintense on the spin-echo sequence
      without contrast injection; it was undetectable on the same sequence in 2 cases.
      In 4 cases the lesion was contrast-enhanced after gadolinium injection. Using
      millimetric sections enables small-size adenomas (2.5 x 3 mm) to be visualized.

PMID- 8308542
TI  - Functional exploration of brain vessels by MRI. Usefulness of presaturation
      techniques.
AB  - The authors report an original method to explore vascular structures. This method
      combines the presaturation technique with gradient-echo vascular imaging, and it
      makes it possible to obtain qualitative data complementing those obtained by
      digital subtraction angiography in cerebral vascular pathology.

PMID- 8308541
TI  - MRI exploration of the intrapetrous facial nerve.
AB  - We report our experience of intrapetrous facial nerve evaluation in 33 patients
      examined by three-dimensional MRI (3D-FT) with intravenous gadolinium injection.
      The examinations were performed by a 1 Tesla magnet, using Flash and Turbo-Flash
      sequences which enabled us to obtain contiguous millimetric sections and to make
      reconstructions in all planes. Among these 33 patients, 31 had facial palsy and 2
      a facial nerve lesion without clinical signs and discovered by chance. Facial
      palsy had started rather abruptly in 26 cases. It was either idiopathic (n = 20)
      or caused by herpes zoster (n = 1), injuries (n = 2), metastasis (n = 1) and
      tumour (n = 1); it was concomitant with a granuloma in 1 case. Five patients seen
      or explored late had congenital cholesteatoma (n = 2), facial nerve neurinoma (n
      = 2) or persistent idiopathic facial palsy (n = 1). There was no contrast
      enhancement in "chronic" non tumoral facial palsy. All tumours (neurinoma,
      neurofibroma, metastasis) were contrast-enhanced, as were the 2 cases of
      traumatic palsy and the case with granuloma of the labyrinth. In acute idiopathic
      facial palsy (n = 20), contrast enhancement was demonstrated in 11 patients;
      among these, recovery was complete at 2 months in 1 case and incomplete in 9
      cases; 1 patient was lost sight of. In the 9 patients without contrast
      enhancement, recovery was complete in 7; 2 patients were lost sight of. This
      study shows that minute lesions of the facial nerve can be detected with
      millimetric MRI T1-weighted sequences and contrast enhancement. It also suggests
      that contrast enhancement has some prognostic value in patients with acute
      idiopathic facial palsy.

PMID- 8308543
TI  - Concentric MR patterns in multiple sclerosis. Report of two cases.
AB  - We report two cases of multiple sclerosis with concentric patterns of
      demyelinated foci on MR images. These were compared with the pathological data of
      Balo's disease. The T2-weighted MR images displayed alternating high and low
      signal areas which probably corresponded to the concentric type of demyelination.
      Our two cases were characterized by their acute onset and their regression
      following corticosteroid therapy. This suggests that Balo's disease may be a
      transient disease and not always associated with a fatal course.

PMID- 8308544
TI  - MRI of acute disseminated encephalomyelitis after coxsackie B infection.
AB  - Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating condition of
      the central nervous system, usually developing after a viral infection or
      vaccination. We report a case of ADEM predominantly affecting the spinal cord in
      an 8-year old boy evaluated by MRI. The radiographic picture consisted of
      multiple focal lesions of the spinal cord, a left posterior thalamic lesion and a
      subcortical right posterior parietal lesion. These lesions regressed several
      weeks after corticosteroid treatment. The clinical presentation, the laboratory
      results and the radiological findings suggest the diagnosis of ADEM secondary to
      viral infection by Coxsackie B.

PMID- 8308545
TI  - MRI evaluation of sacral cysts.
AB  - Sacral cysts or intrasacral sacral meningeal cysts constitute a well-defined
      entity. Their clinical presentation is protean. Few cases have been reported
      concerning their MR aspects. From a series of six patients, the authors present
      the MR images. MRI is the examination of choice to demonstrate their liquid
      content. MRI provides a good evaluation of the lesion, and sagittal images show
      the intrasacral development. MRI scan appears to be superior to CT scan.

PMID- 8308546
TI  - Thoracic disc herniation and spinal cord compression. MRI and gadolinium
      enhancement.
AB  - The authors present a study of 6 patients aimed at assessing the role of Magnetic
      Resonance Imaging with gadolinium-enhancement in the diagnosis of thoracic disc
      herniation. The results of MRI were compared with the findings of computed
      tomography, myelography and surgery. In two patients, the signal from the
      herniated disc was so low on all sequences that thoracic disc herniation was
      diagnosed only on the mass effect on the cord. The anterior longitudinal epidural
      venous plexus (AEVP) is displaced posteriorly and thickened in case of thoracic
      disc herniation. Gadolinium-enhancement of AEVP was marked in these conditions,
      giving a "tent-like" round configuration, or "lifted band" appearance. The exact
      volume and mass effect of the thoracic disc herniation were assessed by T1
      enhanced images on the sagittal and axial planes.

PMID- 8308548
TI  - Sacral pseudomeningocele and Marfan's disease. One case.
AB  - The authors report a case of sacral pseudomeningocele discovered by chance in a
      29-year old male patient presenting with Marfan's disease. In this disease, such
      abnormalities are common and due to excessive fragility. of the dura mater. CT
      and MRI provide an accurate morphological analysis and a complete evaluation of
      lumbosacral osteomeningeal abnormalities.

PMID- 8308547
TI  - Integrated imaging system for stereotactic neurosurgery.
AB  - Talairach's method remains the most universal of all stereotactic methods. It
      makes it possible to go back to an examination left interrupted, but above all,
      it provides multiple lateral and coronal approaches in matters of epilepsy, radio
      isotopes or photobiology. The advances achieved in modern imaging methods,
      notably CT and MRI, and the performance of modern computers have enabled us to
      devise an integrated imaging system meant to accelerate and make feasible
      calculations of penetrating trajectories, according to the position of the target
      as previously defined by CT and MRI sections, and taking into account the
      position of vessels given by angiography. The principal options we selected were:
      transfer onto video tapes of teleangiographic films and introduction of CT and
      MRI images obtained either from films or directly in digits on cartridges or
      networks. The system includes an advanced PC-type microcomputer with 8 memories
      of 1,024/1,024 images: 4 mega octets random access memories and a hard disc of
      150 mega octets; 2 high-resolution screens to present the images, dialogue tools
      (alphanumeric screen, keyboard, trackball) and the usual peripherals. Our system
      performs three main functions: it acquires images to create or complete the
      patient's records; it exploits the images by calculating the parameters required
      for operations; it handles the records through the various peripherals of the
      system. Our system can retrace the proportional 3D squaring according to the CA
      CP distance calculated from ventriculography or MRI, and calculates the position
      of the SEEG electrodes. The stereoscopic effect is obtained by means of glasses
      with liquid crystal obturator from two angiographic series: one orthogonal, the
      other 6 degrees out of phase. The daily use of this system on more than 50
      patients has shown that it is accurate and reliable, irrespective of the makes of
      CT and MRI machines.

PMID- 8308549
TI  - Magnetization transfer imaging in vivo study of normal brain tissues and
      characterization of multiple sclerosis and experimental allergic
      encephalomyelitis lesions.

PMID- 8308550
TI  - Biodistribution and dosimetry of samarium-153-EDTMP.

PMID- 8308552
TI  - If it ain't broke ... break it!

PMID- 8308551
TI  - Specialty maldistribution. The next nursing crisis?
AB  - Clinical specialty maldistribution is a problem in the United States due, in
      part, to ongoing supply and demand problems created by the nursing shortage.
      Although the extent of difficulty is unclear, predictions of future shortages in
      some specialties are startling. If unresolved, maldistribution may affect quality
      of care or result in rationing of care in some specialties areas.

PMID- 8308553
TI  - Modern day pirates. Software users and abusers.
AB  - Although the use of computers for word processing and spreadsheet analysis is
      widespread, other less well-known uses can also increase efficiency and
      productivity. In this bimonthly column, Dr. Nicoll discusses a variety of
      computer applications to help the nurse executive catch up, keep up, and get
      ahead.

PMID- 8308554
TI  - Rural magnet hospitals of excellence. Part 1.
AB  - Although almost half of the hospitals in the United States are rural and small,
      they are often not seen as leaders in innovation. However, many practices just
      now being adopted by large hospitals have been used in rural hospitals for many
      years. To understand excellence in rural hospitals, the authors present a study
      of rural hospitals of excellence, using procedures from the 1982 Magnet Hospitals
      Study. Part 2 will be published in the February issue.

PMID- 8308555
TI  - Using licensed vocational nurses to provide telephone patient instructions in a
      health maintenance organization.
AB  - A pilot project was initiated at Kaiser Permanente Medical Offices in Fairfield,
      California, to determine whether licensed vocational nurses, working with
      registered nurses, can effectively and safely provide selected patient
      instructions by telephone to adult medical patients. We describe the environment,
      funding, implementation process, consultants' major findings, and results of the
      project's impact on staff and operations.

PMID- 8308556
TI  - Mock survey. Methodology for measuring compliance and facilitating change.
AB  - Every nurse executive is responsible for maintaining compliance to current
      externally established standards. As standards change, the nurse executive must
      evaluate the organization, making sure it continues to demonstrate compliance.
      This article describes how one organization used the Joint Commission on
      Accreditation of Healthcare Organizations' Agenda for Change as an opportunity to
      examine its nursing practice. The process included: 1) analyzing compliance to
      the 1991 standards; 2) developing an action plan to address deficiencies; and 3)
      developing and conducting a mock survey to monitor and evaluate effectiveness of
      the action plan. Increased staff comfort with the survey process, monitoring
      tools, and data regarding compliance to standards were the primary outcomes of
      this process. Leadership development, team building, and networking were also
      outcomes.

PMID- 8308557
TI  - The right thing: past & future heroes.

PMID- 8308558
TI  - Quality of work life in home care. The contribution of leaders' personal concern
      for staff.
AB  - The process of healthcare restructuring is creating substantial stress for
      healthcare organizations and professionals. As the health system focuses on
      issues associated with restructuring, concern for staff may be minimized when
      nursing administrators and other healthcare leaders address contextual pressures
      and their impact on service delivery. The authors examine how leaders' personal
      concern for nurses and homemakers contributes to quality of working life in home
      health. Strategies aimed at enhancing personal concern for staff are discussed
      from the perspective of transformational leadership.

PMID- 8308559
TI  - The emerging role of the nurse manager. Implications for educational preparation.
AB  - What trends are evident in redesigning the nurse manager role and what will it
      look like in the year 2000? The author compares data from several different
      sources in identifying trends. The data suggest that the nurse manager role will
      continue to increase in complexity and importance. Implications of trends for
      graduate programs preparing nurse managers and suggested guidelines for planning
      programs are detailed.

PMID- 8308560
TI  - The other side of shared governance.

PMID- 8308561
TI  - Advanced practice roles in the managed care environment.
AB  - The role of the advanced practice nurse is based on expert clinical knowledge and
      skill and is practiced in multiple settings. As healthcare reform emerges, the
      context in which healthcare is delivered changes. The authors describe a creative
      approach to packaging and marketing the services of advanced practice nurses to
      the customers of the managed care system.

PMID- 8308562
TI  - Purchasing information technology solutions: what should you be looking for?

PMID- 8308563
TI  - Perspectives on public health nursing. Interview by Pamela Scott.

PMID- 8308564
TI  - The world's health problems.

PMID- 8308565
TI  - Regulation of fatty acid oxidation in heart.
AB  - The control of fatty acid oxidation in heart is reviewed with special emphasis on
      the energy-linked regulation of this process. Studies with perfused working
      hearts and isolated mitochondria have revealed an inverse relationship between
      the energy-dependent rate of fatty acid oxidation and the intramitochondrial
      ratio of [acetyl-CoA]:[free CoA] at sufficiently high concentrations of fatty
      acids. Studies with isolated enzymes demonstrated a strong inhibition of 3
      ketoacyl-CoA thiolase by acetyl-CoA at low concentrations of free CoA. Together
      these observations prompted the proposal that the rate of fatty acid oxidation is
      tuned to the energy demand of heart via the regulation of 3-ketoacyl-CoA thiolase
      by the [acetyl-CoA]:[free CoA] ratio. Evidence in support of this regulatory
      model has been obtained with isolated rat heart mitochondria in which either the
      activity of 3-ketoacyl-CoA thiolase was decreased by use of mechanism-based
      inhibitors or the intramitochondrial ratio of [acetyl-CoA]:[free CoA] was
      adjusted with L-carnitine. Because intermediates of beta-oxidation normally do
      not accumulate in mitochondria, it remains unclear how the entry of fatty acyl
      CoA into the beta-oxidation spiral is tuned to the activity of 3-ketoacyl-CoA
      thiolase. A control of fatty acid oxidation in heart via the regulation of
      carnitine palmitoyltransferase I by malonyl-CoA has not been established even
      though malonyl-CoA is present in this tissue and strongly inhibits myocardial
      carnitine palmitoyltransferase I.

PMID- 8308566
TI  - A very low intake of fat is required to decrease fecal bile acid concentrations
      in rats.
AB  - The purpose of this study was to determine the effect of different amounts of
      dietary fat on colonic cell proliferation and fecal bile acid concentrations.
      Thirty-nine male Sprague-Dawley rats were randomly assigned to three diets (13
      rats per diet) containing 5, 10 and 20 g butter/100 g diet. Diets were fed for 3
      wk. As fat intake increased, total fecal fat excretion remained constant. When
      dietary fat was decreased from 20 to 10 g/100 g diet, total fecal bile acid
      concentrations tended to increase 14.5%. However, a further reduction to 5 g
      butter/100 g diet significantly decreased fecal total bile acid concentration by
      48% from the concentration in feces of rats fed 10 g butter/100 g diet. The
      concentration of deoxycholate (considered a highly promotive bile acid) was not
      reduced unless the amount of fat in the diet was reduced to 5 g/100 g. Labeling
      index was used as an intermediate marker for colon carcinogenesis. For
      deoxycholate, a decrease of fat intake to 5 g/100 g diet decreased the cecal
      labeling index relative to those of rats fed 10 or 20 g butter/100 g diet. These
      data indicate that decreasing the dietary fat from 20 to 10 g/100 g does not
      decrease fecal bile acid concentration or colonic cell proliferation, but some
      effects are seen in rats fed 5 g butter/100 g diet.

PMID- 8308567
TI  - Rats fed high fat diets with increased calcium levels have fecal bile acid
      concentrations similar to those of rats fed a low fat diet.
AB  - The mechanism by which calcium may protect against colon carcinogenesis was
      studied in rats fed three levels of calcium (0.5, 1.0 and 1.5 g/100 g diet) and a
      high butter diet (20 g/100 g). Results were compared with values obtained using a
      low butter diet (5 g/100 g) supplemented with 0.5 g Ca/100 g diet. Concentration
      and relative proportions of individual fecal bile acids were determined by gas
      chromatography, and in vivo colonic cell proliferation was assessed using
      [3H]thymidine. Total fecal output and total fecal lipids increased as dietary
      calcium increased. When calcium supplementation remained at 0.5%, raising the
      level of fat in the diet increased the fecal concentrations of deoxycholate,
      omega-muricholate and total bile acids. However, when the level of fat
      supplementation remained constant at 20 g/100 g diet, but dietary calcium was 1.0
      or 1.5 g/100 g, the concentration of these bile acids returned to the level found
      in feces of rats fed the low fat diet. Despite the significant decrease in the
      concentrations of certain fecal bile acids with increasing calcium
      supplementation, these differences were not reflected in substantive changes in
      epithelial cytokinetics. These data show that in rats fed high butter diets, 1.0%
      calcium is sufficient to lower total bile acid concentration and the
      concentrations of certain individual bile acids to those found in feces of rats
      fed low fat diets. Despite the significant effects of calcium on bile acid
      concentrations, minimal effects were observed on indices of colonic cell
      proliferation.

PMID- 8308568
TI  - Estimates of trace element intakes in Chinese farmers.
AB  - Epidemiologic data on the average daily human dietary intake of the trace
      elements nickel, cadmium, molybdenum and silicon are scarce, worldwide, primarily
      because foods consumed vary widely over days and seasons. Available full year
      food allocation records for farmers in rural areas of China provide an unique
      opportunity to estimate dietary trace elements. In 1988, we measured the
      concentration of zinc, copper, iron, cadmium, nickel, molybdenum, silicon and
      selenium in different foods by using food samples collected from 232 villages
      (distributed among 21 communes). These measurements, combined with the food
      consumption information from existing food allocation records in each commune for
      an entire year, allowed us to estimate the average daily consumption of these
      trace elements by Chinese farmers. With one exception (an association of zinc and
      esophageal cancer), the variation of dietary trace elements did not show any
      association with mortality from several common diseases. The estimates for some
      of the dietary trace elements from some subpopulations were either less or more
      than current recommendations. No increases in mortality were found, however, from
      diseases normally associated with either dietary deficiencies or excesses of
      these elements.

PMID- 8308569
TI  - Factors associated with perceived insufficient milk in a low-income urban
      population in Mexico.
AB  - Survival analysis and logistic regression were used to identify factors
      associated with the onset of perceived insufficient milk among 165 healthy
      mothers who planned to breast-feed and gave birth by vaginal delivery, without
      complications, to a healthy term infant in either a nursery (n = 58) or a rooming
      in-hospital where formula supplementation was not allowed (n = 107). Women were
      interviewed in the hospital and at 1 wk, 2 mo and 4 mo postpartum. Women from
      both hospitals were similar in socioeconomic, demographic, anthropometric,
      previous infant feeding experience and prenatal care variables. Eighty percent of
      the women reported perceived insufficient milk at some point during the study.
      The cue interpreted most often as indicating insufficient milk was the crying of
      the infant. Multivariate analyses indicated that lack of confidence in breast
      feeding, delayed onset of milk production, maternal education, multiparity, sore
      nipples, early introduction of formula to the previous child and mother breast
      fed as a child were significantly associated (P < 0.05) with perceived
      insufficient milk. Among women who reported perceived insufficient milk before 1
      wk, breast-feeding confidence and maternal education interacted with the hospital
      in which they delivered.

PMID- 8308570
TI  - Intake of 25 g of soybean protein with or without soybean fiber alters plasma
      lipids in men with elevated cholesterol concentrations.
AB  - Twenty-one mildly hypercholesterolemic men consumed a diet that was low in fat (<
      30% of energy) and cholesterol (300 mg/d) and were given muffins containing 25 g
      protein + 20 g dietary fiber daily from either isolated soybean protein + soybean
      cotyledon fiber, isolated soybean protein + cellulose, casein + soybean cotyledon
      fiber or casein + cellulose. All subjects progressed through the low fat, low
      cholesterol baseline period, lasting 2 wk, and then through all four dietary
      treatments, lasting 4 wk each, according to a Latin square design. Plasma
      concentrations of total, LDL, HDL and VLDL cholesterol, total and VLDL
      triacylglycerols, and apolipoprotein A-I and B were measured at the end of each
      period. When data from all subjects were analyzed, dietary treatments did not
      influence lipemia; however, in subjects with initial total cholesterol
      concentrations > 5.7 mmol/L, both isolated soybean protein treatments resulted in
      significantly lower total cholesterol compared with the two casein treatments (P
      < 0.05). In addition, a negative linear relationship was observed when a
      subject's total or LDL cholesterol change after each of the soybean treatments
      was regressed against the subject's baseline cholesterol concentration (P <
      0.05). Apolipoprotein A-I varied dependent on baseline cholesterol with no
      apparent pattern, whereas apolipoprotein B levels were not affected. Results
      indicate that consumption of 25 g soybean protein/d is associated with lower
      total cholesterol concentrations in individuals with initial cholesterol
      concentrations > 5.7 mmol/L.

PMID- 8308571
TI  - Carbohydrate utilization by rainbow trout is affected by feeding strategy.
AB  - A 16-wk experiment was conducted to compare the utilization of four carbohydrates
      by rainbow trout (Oncorhynchus mykiss) fed either continuously or four meals
      daily. The carbohydrates were glucose, maltose, dextrin and raw cornstarch, and
      were included at 32 g/100 g diet. Average initial body weight of the fish was 5.5
      g, and fish were fed at a restricted rate of 2.0% body wt/d. Significant (P <
      0.05) interactions between feeding strategy and carbohydrate were observed only
      for specific growth rate, final body weight, feed efficiency, and protein and
      energy retained. These measurements as well as whole-body moisture and lipid
      concentrations were also significantly higher in the continuously fed trout than
      in the meal-fed trout. Liver weight:body weight ratio, liver glycogen
      concentration, and liver lipogenic enzyme activities generally were higher in the
      continuously fed trout than in the meal-fed trout. Trout fed the glucose diet and
      those fed the maltose diet had higher specific growth rates, final body weights,
      feed efficiencies, energy retained, and whole-body and visceral moisture and
      lipid concentrations than those fed the starch diet. Trout continuously fed the
      glucose and maltose diets also had higher glucose-6-phosphate dehydrogenase and 6
      phosphogluconate dehydrogenase activities than those continuously fed the starch
      diet. The higher protein and energy retained and the higher lipogenic enzyme
      activities in the continuously fed fish compared with the meal-fed fish showed
      that in trout growing slowly due to a restricted ration, continuous feeding
      improved the carbohydrate utilization and increased lipid storage by enhancing
      lipogenesis.

PMID- 8308572
TI  - Jejunal glucose absorption is enhanced by epidermal growth factor in mice.
AB  - The effects of epidermal growth factor on intestinal glucose transport were
      examined in mice. Glucose transport measurements were performed using an in vitro
      assay system that estimated the rate of accumulation of [3H]3-O-methyl-D-glucose.
      In Experiment 1, two-mo-old male and female mice were subcutaneously injected
      once daily with 0, 150 or 300 micrograms epidermal growth factor/kg body weight
      for 3 d. Jejunal glucose active transport was increased in a dose-dependent
      manner. There were no gender-related differences in intestinal glucose transport
      or the response to exogenous epidermal growth factor. In Experiment 2, 2-, 10-
      and 18-mo-old mice were administered 0 or 300 micrograms epidermal growth
      factor/kg body weight using a treatment similar to that used in Experiment 1.
      Active intestinal glucose transport was 30% greater in response to epidermal
      growth factor in each of the three age groups. Ouabain-sensitive and -insensitive
      jejunal oxygen consumption was increased in response to epidermal growth factor
      such that total jejunal respiration was stimulated 15 to 31%. The epidermal
      growth factor related percentage increase in glucose absorption was similar to
      the percentage increase in oxygen consumption such that the apparent energetic
      efficiency of glucose transport was unaffected. In both experiments, the active
      component of glucose transport was increased by epidermal growth factor while
      passive transport was not affected. Jejunal morphology and mucosal DNA and
      protein concentration were not altered by epidermal growth factor treatment.
      Epidermal growth factor-induced increases in intestinal absorption was not
      attributable to mucosal hyperplasia.

PMID- 8308573
TI  - Vitamin C deficiency causes hematological and skeletal abnormalities during fetal
      development in swine.
AB  - The influence of maternal vitamin C deficiency on fetal development was studied
      in swine with a hereditary lack of ability to synthesize ascorbic acid (OD pigs).
      Thirteen pregnant sows homozygous (od/od) for the defect were depleted of
      ascorbic acid for 24 to 38 d at various stages of gestation. Six normal (OD/OD)
      sows were used as controls. Only a few experimental sows showed clinical symptoms
      of vitamin C deficiency. Nevertheless, severe pathological changes were seen in
      the uterus and fetuses. Characteristic findings were hemorrhages and hematomas in
      both fetal and maternal placenta, and general edema and subcutaneous hemorrhages
      in the fetuses. Similarities were noted to the abruptio placentae syndrome in
      women. Depletion of vitamin C resulted in a pronounced decline in ascorbic acid
      concentration in most maternal and fetal organs as well as in plasma and
      embryonic fluids. No morphological malformations were found in the fetuses, but
      the ossification of the skeleton was severely deranged. Macroscopically the
      lesions comprised swelling of the costochondral junction and separation of the
      epiphysial cartilage from the spongiosa in ribs and limb bones. Another
      characteristic finding was loosening of the periost from the cortex, often
      resulting in subperiosteal bleedings. Microscopically normal osteoblasts were few
      and the formation of osteoid defective.

PMID- 8308574
TI  - Production of proline-rich proteins by the parotid glands of rats is enhanced by
      feeding diets containing tannins from faba beans (Vicia faba L.).
AB  - Feeding a casein-based diet with either 400 g/kg of tannin-containing faba bean
      hulls (Vicia faba L.) (1.41% condensed tannins) or 60 g/kg of a tannin-rich hull
      extract of faba beans (1.99% condensed tannins) to rats over a period of 7 d
      resulted in a 2.6 and 1.5 fold increase in weight of the parotid glands,
      respectively, (P < 0.05) and a corresponding 5.5 and 3.7 fold increase in the
      level of proline-rich proteins in the glands (P < 0.05). In a dose-response
      experiment, increasing the level of tannin-rich hull extract in the diet (0.0,
      3.8, 7.5, 15.0, 30.0 and 60.0 g/kg) resulted in a linear increase in both the
      relative size of parotid glands (R2 = 0.90; P < 0.05) and the quantity of proline
      rich proteins in the glands (R2 = 0.89; P < 0.05). The apparent digestibility of
      total (R2 = 0.97) and individual amino acids (R2 varied from 0.27 to 0.99)
      decreased linearly (P < 0.05). The quantity of proline-rich proteins in the cecum
      of rats was estimated from the decrease in digestibility of proline, glycine and
      glutamic acid. The estimated secretions of proline-rich proteins, when calculated
      on the basis of the three respective amino acids, were 3.5, 3.5 and 3.9 mg of
      proline-rich proteins per 10 mg of additional hull extract (21.8% condensed
      tannins). The results indicate that tannins from faba beans stimulate the parotid
      glands to increase the secretion of proline-rich proteins in rats. The proline
      rich proteins then interact with dietary condensed tannins to reduce their
      antinutritional effects.

PMID- 8308575
TI  - Intragastric tryptophan reduces glycemia after glucose, possibly via glucose
      mediated insulinotropic polypeptide, in early-weaned piglets.
AB  - The aim of this experiment was to investigate the influence of oral tryptophan on
      insulin, glucose-mediated insulinotropic polypeptide and glucose concentrations
      in early-weaned piglets. Piglets were given by intragastric infusion, at the same
      level of feeding, either a tryptophan-deficient or tryptophan-adequate diet for
      22 d. During the experiment blood samples were taken after intragastric infusion
      of 1) the accustomed meal, 2) a glucose plus tryptophan load and 3) a glucose
      load. Plasma samples were analyzed for insulin, glucose-mediated insulinotropic
      polypeptide, glucose and lactate. After the accustomed meal plasma insulin
      concentrations were augmented and liquid gastric emptying faster in pigs fed
      tryptophan-adequate compared with tryptophan-deficient diets (P < 0.05) but
      glucose-mediated insulinotropic polypeptide, glucose and lactate were unaffected.
      The addition of tryptophan to a glucose load increased glucose-mediated
      insulinotropic polypeptide and reduced glucose in both tryptophan-adequate and
      tryptophan-deficient diet fed pigs (P < 0.05). Piglets adapted to the tryptophan
      adequate diet had a greater glucose-mediated insulinotropic polypeptide response
      to intragastric glucose plus tryptophan than piglets adapted to the tryptophan
      deficient diet. Adaptation to a tryptophan-adequate diet seems to increase the
      release of glucose-mediated insulinotropic polypeptide due to infusion of a
      tryptophan-adequate compared with a tryptophan-deficient diet. The addition of
      tryptophan to a glucose load reduces the level of glycemia, possibly through
      glucose-mediated insulinotropic polypeptide-mediated glucose disposal.

PMID- 8308576
TI  - Size of the zinc pools that exchange rapidly with plasma zinc in humans:
      alternative techniques for measuring and relation to dietary zinc intake.
AB  - A relatively simple technique was used to estimate the size of the combined pools
      of zinc with which plasma zinc exchanges within 2 d (EZP). EZP size was
      determined from the amount of isotope introduced into the plasma and the
      coefficient of the simple exponential decay function fitting enrichment data
      between d 3 and 9 after isotope administration. Using data from 11 healthy
      adults, comparisons were made of EZP size estimations using oral and intravenous
      isotopes (r = 0.93 using urine) and urine and plasma enrichment (r = 0.85 for
      intravenous). EZP size estimations from urine and plasma enrichment following
      intravenous isotope administration were 2.35 +/- 0.84 and 2.83 +/- 0.86 mmol,
      respectively (mean +/- SD, P < 0.01). EZP size correlated with habitual dietary
      zinc intake (partial r = 0.74, P < 0.02). Cumulative declines in EZP size in two
      healthy adults after 3 wk of consuming a moderately zinc-restricted diet followed
      by 1 wk of severe zinc restriction were 26 and 32%. These results indicated that
      EZP size is dependent on dietary intake. We conclude that this technique is
      adequate to demonstrate EZP differences that are of nutritional and physiological
      interest. EZP size estimates can be obtained using orally or intravenously
      administered isotope and using plasma or urine enrichment data.

PMID- 8308577
TI  - Quantifying the vitamin K requirement of juvenile marine shrimp (Penaeus monodon)
      with menadione.
AB  - A feeding trial was conducted to estimate the optimum dietary vitamin K
      requirement for juvenile marine shrimp, Penaeus monodon. Purified diets with
      eight levels (0, 5, 10, 20, 50, 80, 160 and 320 mg/kg) of supplemental menadione
      were fed to P. monodon (mean weight 1.33 +/- 0.05 g) for 12 wk. Each diet was fed
      to three replicate groups of shrimp. Shrimp fed diets supplemented with vitamin K
      (5-320 mg/kg) had significantly (P < 0.05) higher weight gain and feed efficiency
      than those fed the unsupplemented control diet. Shrimp fed diets supplemented
      with > or = 50 mg/kg vitamin K had higher protein efficiency ratios than shrimp
      fed the control diet. Calcium deposition in shrimp generally increased as dietary
      vitamin K supplementation increased. Vitamin K-dependent carboxylase activity was
      highest in shrimp fed the control diet, followed by shrimp fed 5-160 mg
      menadione/kg diet, and lowest in those fed 320 mg menadione/kg diet. Vitamin K
      dependent protein precursor concentrations were high in shrimp fed 0-10 mg
      menadione/kg diet, lower in those fed 20 mg/kg, and lowest in shrimp fed > or =
      50 mg/kg diet. Protein efficiency ratio and vitamin K-dependent protein precursor
      concentration analyzed by broken-line regression indicated that the adequate
      dietary vitamin K concentration in growing P. monodon is 30-40 mg/kg diet.

PMID- 8308578
TI  - Dietary tannins from cowpeas and tea transiently alter apparent calcium
      absorption but not absorption and utilization of protein in rats.
AB  - Tannins reportedly alter absorption and utilization of protein and minerals. The
      present study investigated the effect of tannins extracted from 'Mississippi
      Silver' cowpeas and black tea when incorporated into nutritionally balanced
      diets. Condensed tannins were incorporated into the diet of weanling male Sprague
      Dawley rats at 0.0, 0.0057, 0.0171 and 0.057 g/100 g diet for 28 d. Ingestion of
      tannin from cowpeas or tea did not change significantly growth rate, protein
      efficiency ratio, apparent protein digestibility, nitrogen excretion, relative
      liver weight, or nitrogen concentration of liver. During d 11-18, apparent
      calcium absorption was lower in rats fed the medium and high levels of cowpea
      tannin and in those fed all levels of tea tannin compared with the control group.
      By wk 4, no differences were observed in apparent calcium absorption among
      treatment groups. Apparent magnesium absorption was not affected by dietary
      treatment, nor was femur content of calcium or magnesium. We conclude that at the
      levels of condensed tannins fed, a short-term reduction of apparent calcium
      absorption occurred; however, by wk 4 calcium absorption was comparable to that
      of the control group. The acute change that occurred in apparent calcium
      absorption did not influence bone calcium content.

PMID- 8308579
TI  - Formula 18:2(n-6) and 18:3(n-3) content and ratio influence long-chain
      polyunsaturated fatty acids in the developing piglet liver and central nervous
      system.
AB  - Docosahexaenoic acid and arachidonic acid are deposited in large amounts in the
      developing central nervous system, and concentrations are particularly high in
      synaptic plasma membrane and retina ethanolamine phospholipids. Arachidonic acid
      and docosahexaenoic acid are present in human milk. The precursors linoleic
      [18:2(n-6)] and alpha-linolenic [18:3(n-3)] acid, but not arachidonic acid or
      docosahexaenoic acid, are present in formulas. Desaturation and elongation of
      18:2(n-6) and 18:3(n-3) to arachidonic acid and docosahexaenoic acid,
      respectively, depend on the dietary content and ratio of 18:2(n-6) and 18:3(n-3),
      but appropriate levels and ratios of 18:2(n-6) and 18:2(n-3) for formula are not
      well defined. The effect of formula with 1 or 4% fatty acids 18:3(n-3) and 16, 30
      or 35% fatty acids 18:2(n-6) on synaptic plasma membrane and retina ethanolamine
      phospholipid fatty acids was therefore studied in piglets, with reference to
      piglets fed milk. Piglets fed 4% fatty acids 18:3(n-3), but not those fed 1%
      fatty acids 18:3(n-3), had similar central nervous system docosahexaenoic acid
      levels but had significantly lower brain weights than piglets fed sow milk.
      Synaptic plasma membrane and retina arachidonic acid were lower in piglets fed
      the formulas with 4% rather than 1% fatty acids 18:3(n-3). The dietary 18:3(n-3)
      content, rather than the 18:2(n-6) to 18: 3(n-3) ratio, seemed more important for
      deposition of docosahexaenoic acid in brain. However, synaptic plasma membrane
      and retina docosahexaenoic acid levels were further reduced in piglets fed 1%
      fatty acids 18:3(n-3) (0.4% energy) with 30% rather than with 16% fatty acids
      18:2(n-6). The need for further study of upper limits of dietary 18:3(n-3) during
      development is suggested.

PMID- 8308580
TI  - Increasing calcium intakes lower urinary concentrations of phosphorus and
      magnesium in adult ovariectomized cats.
AB  - The effect of dietary calcium level on the fecal and urinary excretion of
      calcium, phosphorus and magnesium was studied in adult cats. Ovariectomized cats
      were fed purified diets containing 3.2, 4.8, 9.5 or 19.3 mmol calcium/MJ in a 4 x
      4 wk crossover study. During the experiment, balance studies were performed and
      blood samples were taken. The adult ovariectomized cats maintained calcium
      balance at all four levels of calcium tested. Extra dietary calcium, in the form
      of CaCO3, caused a slight increase in urinary pH. Urinary concentrations of
      phosphorus and magnesium dropped, but that of calcium remained unchanged, when
      the cats were fed diets with increasing calcium levels. The percentages of
      apparent absorption of phosphorus and magnesium fell when calcium intake was
      raised. The dietary calcium level did not affect plasma concentrations of
      calcium, magnesium and phosphorus or plasma activity of alkaline phosphatase.

PMID- 8308581
TI  - Dietary cholesterol supplementation improves growth and behavioral response of
      pigs selected for genetically high and low serum cholesterol.
AB  - We hypothesized that, in pigs selected for low (L) or high (H) serum cholesterol
      for four generations, neonatal endogenous cholesterol synthesis would be
      sufficient to meet requirements for brain and body growth. In Experiment 1, eight
      16-wk-old L pigs received a diet with or without 200 mg cholesterol/100 g diet
      for 35 d. Supplemented pigs grew approximately 25% faster and had a significantly
      greater concentration of free cholesterol in the cerebrum. In Experiment 2, 16 H
      and 16 L newborn pigs were fed a milk replacer with or without 200 mg
      cholesterol/100 g diet for 28 d. Pigs fed cholesterol had greater average daily
      gain (P < or = 0.09), significantly reduced liver 3-hydroxy-3-methylglutaryl
      coenzyme A reductase activity, and significantly increased cerebral cholesterol
      content than pigs not fed cholesterol. One of three indices of exploratory
      behavior was significantly greater in the L pigs that received cholesterol
      compared with L pigs that did not receive cholesterol. These data suggest that
      these neonatal pigs are unable to produce sufficient cholesterol to meet
      requirements for normal growth and brain development and are dependent on dietary
      cholesterol in milk.

PMID- 8308582
TI  - Ethical issues in separation of the Lakeberg Siamese twins.

PMID- 8308583
TI  - Prenatal maternal indomethacin use resulting in prolonged neonatal renal
      insufficiency.
AB  - The short-term use of indomethacin has been shown to be relatively safe and
      effective in halting premature labor. Its use has been associated with adverse
      renal effects in both the fetal and newborn periods that are generally transient
      and resolve on discontinuation of the drug. However, limited data suggest that
      prolonged prenatal exposure to indomethacin may be harmful to the fetus. We
      report a case of prolonged severe renal dysfunction characterized by
      oligohydramnios and postnatal anuria, azotemia, and ultrasonographic kidney
      abnormalities associated with the long-term prenatal use of indomethacin.
      Although partial resolution was observed, a moderate decrease in renal function
      persists. Prenatal maternal indomethacin use represents a potential cause of
      renal dysfunction in the newborn infant that may be only partially reversible.

PMID- 8308584
TI  - Fluorescence anisotropy of tracheal and oropharyngeal aspirates as an indicator
      of lung disease in neonates.
AB  - Fluorescence anisotropy was assessed in tracheal and oropharyngeal aspirates to
      evaluate its use in the diagnosis of respiratory distress syndrome. Samples from
      31 neonates at birth were purified by using Sephacryl S-300 column
      chromatography. After the addition of the molecular probe, 1,6-diphenyl 1,3,5
      hexatriene fluorescence was measured and anisotropy calculated. Ten neonates with
      normal respiratory function had a mean anisotropy (+/- SD) of 0.226 +/- 0.023.
      Fourteen infants with a diagnosis of respiratory distress syndrome had a mean
      anisotropy of 0.260 +/- 0.014 (p < 0.001). Seven neonates with respiratory
      problems other than respiratory distress syndrome had a mean anisotropy of 0.211
      +/- 0.027 (p < 0.001 vs respiratory distress syndrome). A diagnosis of
      respiratory distress syndrome was associated with higher tracheal fluid
      anisotropy, indicating a qualitative difference in the characteristics of the
      pulmonary surfactant. We conclude that this 30-minute test could help identify
      neonates who benefit from surfactant replacement therapy.

PMID- 8308585
TI  - Neonatal and postneonatal mortality: useful constructs or outdated concepts?
AB  - Infant deaths are traditionally divided into neonatal and postneonatal categories
      by age at death. In the past neonatal deaths were largely caused by perinatal and
      biologic conditions (endogenous causes) and postneonatal deaths resulted from
      nonperinatal conditions, injuries, and socioenvironmental causes (exogenous
      causes). This study explores the congruence between neonatal-endogenous, and
      postneonatal-exogenous causes of infant death, with underlying cause of death
      data for the Wisconsin resident birth cohorts from 1979 to 1986. Although birth
      weight-specific neonatal and postneonatal mortality rates within cause of death
      categories remained stable during the 1980s, differences in the distribution of
      endogenous and exogenous infant deaths by cause of death suggest that the
      neonatal-postneonatal classification is no longer a useful proxy. Although
      neonatal and endogenous infant mortality remain fairly synonymous, postneonatal
      deaths are no longer equivalent to deaths of exogenous causation. Alternatives to
      use of days of life for classifying infant deaths as neonatal or postneonatal
      include dating infant deaths by corrected gestational age, and mortality rate
      during the hospital stay. These approaches should be evaluated as alternatives to
      the neonatal-postneonatal classification.

PMID- 8308586
TI  - Pneumogram recordings and cerebral computed tomography as predictors of the
      severity of infant apnea.
AB  - We studied several predictors of severity of apnea and caretakers' anxiety about
      home cardiorespiratory monitoring in 476 families with infants enrolled in a
      perinatal follow-up program. Thirty-six (8%) of the infants had apparent life
      threatening events at home. These infants were compared with the remaining
      infants, who had benign outcomes. Normal pneumograms and normal cerebral computed
      tomographic scans predicted the absence of significant respiratory problems (99%
      and 100% true negative rates, respectively). Infants with these signs may not
      require home monitoring. This study used a stringent criterion of periodic
      breathing (< or = 3% of quiet time) in defining a normal pneumogram. A more
      common criterion (< or = 10%) would have accurately predicted only 45% and missed
      55% of the infants with life-threatening events. Level of caretakers' anxiety
      about monitoring was related to severity of apnea. Parental anxiety about
      monitoring may have been overestimated in previous research.

PMID- 8308587
TI  - Parental compliance with home apnea monitoring.
AB  - Until now, compliance with home apnea monitoring (HAM) has been assessed by
      parental recall. The availability of monitors with electronic memory allows a
      more objective evaluation of HAM. Fourteen premature infants discharged home from
      the hospital and receiving theophylline and 15 infants not receiving medication
      were studied. Medical and birth records, parent questionnaires, and 1 month of
      electronically recorded data were analyzed. Birth weights of the infants ranged
      from 850 to 2400 gm and gestational age from 26 to 34 weeks. Of 26 parents who
      recalled never leaving their infants unmonitored, 70% missed at least one night,
      30% three or more. During the first month, treated infants were left unmonitored
      21% of the days and 9% of the nights, and untreated babies were unmonitored 32%
      of the days and 15% of the nights. Average daily HAM use was 18 hours for treated
      and 16 hours for untreated (p = 0.19). Two weeks after discharge, the decline in
      use for treated babies was 5% (day and night), whereas for untreated infants the
      decrease was 20% during the day and 15% at night. Lead-related alarms occurred
      with similar frequency (one to two times per day) in both groups. Non-lead
      related alarms were somewhat more frequent for treated (four times per day) than
      for untreated infants (twice daily). Parents' perception of the likelihood of
      severe apnea at the time of discharge influenced HAM use. Little risk prompted 13
      hr/day use and moderate risk 16 hr/day, whereas great perceived risk resulted in
      18 hr/day of monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308588
TI  - Influence of family functioning on maternal-fetal attachment.
AB  - Although the development of a positive relationship between the mother and infant
      most likely begins during pregnancy, the correlates of maternal-fetal attachment
      are poorly understood. This study examined the influence of family functioning on
      maternal-fetal attachment in a sample of varied ethnic and socioeconomic
      backgrounds. The authors surveyed 339 pregnant women in their last trimesters
      with the Family Adaptability and Cohesion Scales-III (FACES-III), Maternal-Fetal
      Attachment Scale (MFA), and a demographic interview. On the basis of
      correlational and regression analyses, the demographic variables of parity,
      ethnicity, age, education, and occupation of primary wage earner correlated
      significantly with maternal-fetal attachment. When entered in a multiple
      regression analysis, parity, ethnicity, and occupation explained 12% of the
      variance in the MFA scores. The FACES-III total score and the subscale scores of
      adaptability and cohesion also correlated significantly with scores on the MFA
      and explained an additional 3% of the variance in the MFA beyond that explained
      by the demographics. Support of positive family dynamics during pregnancy by
      health care workers may potentially increase the quality of maternal-fetal
      attachment.

PMID- 8308589
TI  - Maternal renal impairment after indomethacin tocolysis.
AB  - Indomethacin is widely used to treat both preterm labor and polyhydramnios.
      Although adverse fetal and neonatal reactions have been described, the use of
      indomethacin is not thought to pose a risk to the mother. A case of maternal
      renal function impairment caused by indomethacin therapy for preterm labor at 27
      weeks in a twin pregnancy is presented. The patient was given a 17-day course of
      indomethacin at standard tocolytic doses of 25 mg orally, every 6 hours. She was
      delivered after a diagnosis of chorioamnionitis was made and antibiotics,
      including gentamicin, were instituted. Three days post partum the patient was
      found to have a blood urea nitrogen value of 27 mg/dl and a serum creatinine
      level of 3.2 mg/dl. Maternal renal function rapidly improved after the
      discontinuation of gentamicin. This case represents a potentially serious
      interaction between an aminoglycoside and indomethacin in an otherwise healthy
      woman at no risk of renal disease. Monitoring of renal function is advisable when
      potentially nephrotoxic drugs are given with or soon after indomethacin.

PMID- 8308590
TI  - Infants with chronic lung disease: predictors of mortality at day 28.
AB  - The outcome of infants who were admitted to the neonatal intensive care unit at
      Liverpool Maternity Hospital between January 1980 and December 1989 and who
      developed chronic lung disease (n = 242) was determined. Forty-three (18%) died
      in hospital and 18 (9% of survivors) were discharged with home oxygen therapy.
      The number of days spent receiving supplementary oxygen significantly correlated
      with the number of days of ventilatory support received and the inspired oxygen
      concentration on day 28. Logistic regression analysis revealed that death in the
      hospital was independently associated with being male, and correlated with the
      number of days of ventilatory support received and the inspired oxygen
      concentration on day 28. An equation that predicted the probability of death in
      infants with chronic lung disease was derived and was validated for infants with
      chronic lung disease at another center (Nottingham). This equation may be useful
      clinically and for research.

PMID- 8308591
TI  - Guarantee my child will be "normal" or stop all treatment.

PMID- 8308592
TI  - Traumatic pseudodiverticulum of the pharynx.
AB  - Traumatic pseudodiverticulum of the pharynx is a rare complication of
      endotracheal intubation. Prompt recognition and management will help in reducing
      the morbidity. A case of traumatic pseudodiverticulum of the pharynx in a preterm
      infant and the management with a brief review are reported.

PMID- 8308593
TI  - Toxic epidermal necrolysis in a newborn infant after exposure to adhesive
      remover.

PMID- 8308594
TI  - Combined Rh hemolytic disease and granulocyte alloimmunization causing prolonged
      agranulocytosis in a newborn infant.

PMID- 8308595
TI  - Ventilatory management casebook. Intermittent mandatory ventilation with
      continuous negative pressure for treatment of pulmonary artery hypertension.

PMID- 8308597
TI  - Special imaging casebook. Infantile hemangioendothelioma of the liver.

PMID- 8308596
TI  - Fetal heart rate monitoring casebook. Concealed abruptio placentae.

PMID- 8308598
TI  - Placental pathology casebook. A bidiscoid, monochorionic placenta.

PMID- 8308600
TI  - Four-part displaced proximal humeral fractures: operative treatment using
      Kirschner wires and a tension band.
AB  - Thirty-five patients with four-part displaced proximal humeral fractures and
      fracture-dislocations were retrospectively reviewed from the years 1977-1990.
      Thirty-three patients were available for study. All fractures were treated by
      open reduction and internal fixation allowing early motion. Surgical technique
      was as atraumatic as possible with the goal of restoring normal anatomy of the
      proximal humerus with a minimal fixation system. The fixation device consisted of
      two modified Kirschner wires introduced through the tuberosities and reinforced
      by a tension band wiring. Neer's criteria were used to evaluate results. With a
      mean follow-up of 7 years, results were excellent and satisfactory in 21 cases,
      nonsatisfactory in 10, and poor in two. The most common complication was
      avascular necrosis (nine patients). All cases of fracture-dislocations
      corresponded with the nonsatisfactory and poor results. Because of our results,
      we conclude that in four-part displaced fractures, open reduction and internal
      fixation with our system of osteosynthesis should be indicated initially.
      Prosthetic replacement should be considered as primary treatment in cases with
      marked comminution of the humeral head, in fracture-dislocations, and in patients
      > 75 years of age.

PMID- 8308599
TI  - Pilon fractures: treatment with combined internal and external fixation.
AB  - The purpose of this study was to prospectively evaluate the use of limited
      internal fixation and the application of a hybrid external fixator (tensioned
      wires distally and 5.0 mm half pins proximally attached to a semicircular frame
      without crossing the ankle joint) in the treatment of severe distal tibia
      fractures. This technique involves accurate reduction and fixation of the
      intraarticular component through an incision based over a fracture site followed
      by stabilization of the metaphysis with the hybrid external fixator. We studied
      26 patients 15-55 years of age who were followed for 8-36 months. All fractures
      were within 5 cm of the joint. Seventeen fractures were intraarticular, nine
      extraarticular, and six open. Eleven patients required bone grafting. The average
      time to healing was 4.2 months. Using clinically based criteria, there were 81%
      good and excellent results overall, 70.5% for the 17 intraarticular fractures,
      and 69% for Ruedi type III fractures. Complications included one superficial and
      one deep infection, one 10 degrees varus malunion, and three pin tract
      infections. This method yielded results comparable with previous studies while
      reducing the amount of soft tissue dissection necessary for the placement of
      large plates. Soft tissue complications were infrequent and the goals of early
      motion and fracture stability were not sacrificed.

PMID- 8308601
TI  - Nailgun injuries of the hand.
AB  - Nailgun injuries of the digits and palm are an occupational hazard for
      carpenters. Sixty-five percent of all nailgun injuries have been reported to
      involve the hand. Clinically they can be further classified into three types,
      varying with the injury and the prognosis. Prompt nail removal after i.v.
      antibiotics, minimal wound debridement, operative curettement of the nail tract
      with removal of any foreign material, irrigation, open wound drainage, and
      nonoperative treatment of skeletal injuries resulted in healing without infection
      and with good function in seven cases.

PMID- 8308602
TI  - The location of the sacroiliac joint on the outer table of the posterior ilium.
AB  - Ten cadaveric sacroiliac joints were cleaned of soft tissue and analyzed to
      determine the average location of the sacroiliac joint on the outer table of the
      posterior ilium. The superior and inferior limbs of the joint were characterized
      according to length and width. The longitudinal axis for each limb was determined
      and located on the outer table of the posterior ilium. The location of the
      sacroiliac joint was then characterized with respect to established anatomic
      landmarks. The average lengths of the superior and inferior limbs were 4.4 and
      5.6 cm, respectively. The width of each limb averaged 2.0 cm. The average
      distance from the longitudinal axis of the superior limb to the posterior
      superior iliac spine was 5.5 cm. The average longitudinal axis of the inferior
      limb was 1.2 cm superior to the inferior margin of the posterior inferior iliac
      spine. The angle between the two axes averaged 93 degrees.

PMID- 8308603
TI  - Posterior sacroiliac fixation using a sacral pedicle targeting device: an
      anatomical study.
AB  - This study compares the accuracy of posterior sacroiliac (SI) screw placement
      using a "free-hand" method, without the use of fluoroscopy, versus a specially
      developed targeting device. Posterior SI screws were inserted after exposing the
      iliac wing in five cadavers on one side, and inserted percutaneously with a
      unique targeting device on the opposite side. Fluoroscopy was not used for screw
      or pedicle placement on either side. Computed tomography and dissection results
      were then used to grade screw placement for both sides. A statistically
      significant difference between the sides was found. More importantly, three
      screws on the free-hand side violated major neurovascular structures. The
      regional anatomy was defined: structures most at risk are the iliac vein
      ventrally and the sacral canal dorsally. A highly variable "safe zone" (mean arc
      43 degrees at the S1 level and 30 degrees at the S2 level) was established.
      Inclination of the SI joint was also defined (mean 29 degrees at the S1 level and
      17 degrees at the S2 level). SI screw placement using the specially developed
      targeting device is technically less demanding, requires less soft tissue
      dissection, allows variable placement, and poses minimal risk to major
      neurovascular structures. Our limited clinical experience with the device is
      encouraging. The potential application of this technique to unstable vertical
      shear fractures is appealing.

PMID- 8308604
TI  - Treatment of a central fracture-dislocation of the hip using external fixation
      with iliofemoral distraction.
AB  - Three patients were treated with external fixation with iliofemoral distraction
      as an alternative treatment of comminuted central fracture-dislocations of the
      hip. The patients were mobilized on the first postoperative day and discharged
      from the hospital an average of 10 days postaccident. The frame was left in place
      for 6 weeks while the traction was maintained. Full weight bearing was started 3
      months after the injury. A full range of motion in the injured hip was achieved
      at 4 months postoperation. No signs of avascular bone necrosis were seen during
      follow-up for up to 2 years. The clinical results of the described method were
      good, and it can be used as an alternative method, especially when open reduction
      is contraindicated or complicated.

PMID- 8308605
TI  - Age and sex as determinants of mortality after hip fracture: 3,895 patients
      followed for 2.5-18.5 years.
AB  - Between 1970 and 1985, a total of 3,895 persons > or = 40 years of age were
      treated for hip fracture in a Danish municipality. The female: male ratio was
      2.7. The cumulative survival was estimated and compared with that of the age- and
      sex-matched general population. The analysis showed that (a) the mortality was
      increased compared with the expected mortality, especially during the first year
      (19% for women, 25% for men), but a statistically significant excess mortality
      could be demonstrated up to 10 years after a hip fracture; (b) the mortality
      increased with age, even after adjustment for the expected higher mortality of
      the elderly; and (c) the mortality was higher for men than for women, even after
      adjustment for the expected higher mortality of males. This difference was
      already present after the first 2 weeks among patients > or = 70 years of age.

PMID- 8308606
TI  - Effect of time delay from injury to primary management on the incidence of deep
      infection after open fractures of the lower extremities caused by blunt trauma in
      adults.

PMID- 8308608
TI  - Direct leg lengthening.
AB  - Twenty patients with an average posttraumatic leg length shortening of 4.6 cm
      (range 2.5-9) underwent direct leg lengthening. The operation time averaged 210
      min and the peroperative blood loss was 1,800 ml. Angular and rotational
      malalignment, when present, were corrected. Lengthening averaged 3 cm. At follow
      up, two patients had serious sequelae after vascular injuries. Seven patients had
      postoperative neurological complications, which in four cases resolved
      completely. The time required for solid union of the lengthened segment averaged
      10 months. Bone grafting two or more times was performed in six patients.
      Seventeen patients were assessed an average of 7 years (range 3-10) after
      surgery. Thirteen of these were satisfied with the results of the lengthening.
      Complications of the procedure and/or a remaining major leg length inequality
      could explain the dissatisfaction of the others. A majority of the patients
      complained of low-back pain both preoperatively and at follow-up. Few complaints
      about the joints in the long leg were expressed. Preoperative pain about the hip
      and knee in the short leg existed in more than half of the patients, and these
      complaints were reduced on a weak statistical level at follow-up. Walking ability
      improved in 12 patients, working ability in 10, and recreational activity level
      in eight. Direct leg lengthening is generally regarded as major, demanding
      surgery, entailing potential risks of serious complications, and should be used
      with great care and only in selected cases.

PMID- 8308607
TI  - Heterotopic ossification after femoral intramedullary rodding.
AB  - Heterotopic ossification (HO) after femoral intramedullary rodding is a
      significant complication of the procedure. One hundred eighteen cases of femoral
      roddings performed on 113 patients were available for review. The data were
      computerized and evaluated using univariate analysis and multivariate regression
      analysis. A statistically significant increase of HO was found with male gender,
      increased delay to surgery, and in patients requiring prolonged intubation
      because of their multiple injuries. HO was classified using a modified version of
      the method of Brumback et al. (grades 0-IV). A strong correlation of HO with
      brain injury documented by computed tomography scan was also found to be
      statistically significant for the more severe grades of HO. This group of
      patients had not previously been identified as being at high risk for HO.

PMID- 8308609
TI  - Resonant frequency analysis of the tibia as a measure of fracture healing.
AB  - The Resonant Frequency (RF) of the tibia is proportional to its stiffness. As a
      fractured tibia heals, its RF should increase. The RF was serially determined in
      74 fractured tibias (205 examinations). These were subdivided by fracture
      location and fixation. Fast Fourier transform software generates the RF from data
      obtained with an instrumented impactor and accelerometer. The RF was normalized
      by expressing it as a ratio of the intact tibia. This ratio is called the tibial
      stiffness index (TSI). A 20 point tibial fracture score (TFS) quantitated the
      clinical and radiographic signs of healing. For each group the paired TSI and TFS
      were compared by regression analysis. Except for those fractures limited to the
      proximal fourth of the tibia, the TSI was found to correlate significantly (p =
      0.0001) with the TFS. Fractures without fixation and those with unlocked,
      unreamed tibial nails showed very significant correlation of TSI with TFS (p =
      0.0001). RF analysis was not useful in fractures with locked or reamed tibial
      nails. Examination of tibia with external fixation showed significant correlation
      (p = 0.02) of the TSI with the TFS.

PMID- 8308610
TI  - Closed elbow dislocation and brachial artery damage.
AB  - Damage to the brachial artery associated with closed elbow dislocation but
      without accompanying fracture is rare. Only 25 cases have been reported to date.
      We present a case that responded well to brachial artery vein grafting, and
      review the literature on this subject. Operative repair is recommended in this
      uncommon complication of closed dislocation of the elbow.

PMID- 8308611
TI  - A case of traumatic spino-pelvic dissociation.
AB  - A case of traumatic spino-pelvic dissociation is reported. The unusual fracture
      pattern (grade III-B open left sacroiliac joint fracture dislocation, Denis type
      I longitudinal right sacral fracture, transverse sacral fracture at the S3-4
      level, and a left comminuted pelvic wing fracture) led to a complete dislocation
      of the spine from the pelvis, transection of the left S1 and S2 nerve roots, and
      intrusion of the cranial portion of the spine into the pelvis. The patient
      underwent open reduction internal fixation of the spine and the pelvis in
      combination with general surgical management. Two years postinjury, the patient
      lives independently and walks with one cane.

PMID- 8308612
TI  - An unusual posterior fracture-dislocation of the hip.

PMID- 8308613
TI  - EDI ... a new way to reduce dental expenses.

PMID- 8308614
TI  - Actinic cheilitis.
AB  - Ultraviolet (UV) radiation of the vermilion border of the lips can precipitate
      recurrent herpetic infections, varying degrees of dysplasia, and squamous cell
      carcinoma. UV light also can aggravate certain systemic conditions, such as lupus
      erythematosus, and produce solar urticaria, porphyrias, and drug photosensitivity
      reactions.

PMID- 8308615
TI  - A community-based program to facilitate dental care for senior citizens.
AB  - This article presents findings of a one-year trial which examined a community
      based program in Clinton County, Indiana, to help facilitate entry of senior
      citizens into the oral health care delivery system. A multifaceted approach
      addressed the senior citizens' limited knowledge of oral health care, personal
      barriers to obtaining dental services, and the community's concern for the health
      of older citizens. Program components included oral health education (newspaper
      articles, presentations, pamphlet distribution), personalized patient motivation
      ("Bring-a-Friend" campaign), and oral health screenings (public screenings and
      "Senior Day at the Dentist"). During the study year, 345 patients visited the
      dentist, compared to 179 in the baseline year. Ninety-three participated in the
      two "Senior Day" screenings, and 53 percent of the total 134 screening patients
      returned for follow-up care. Given its experimental nature, the program was a
      success.

PMID- 8308616
TI  - You can forget that gas!

PMID- 8308617
TI  - Still edentulous.

PMID- 8308618
TI  - Varying treatment strategies for reconstruction of maxillary atrophy with
      implants: results in 98 patients.
AB  - This report describes the outcome of maxillary implant reconstruction in 98
      consecutively treated patients assigned to three groups based on the degree of
      maxillary atrophy as noted on radiographic examination and method of treatment.
      In group 1, 33 patients had 83 implants installed following sinus and/or nasal
      mucosal lift procedures. In group 2, 26 patients had 56 implants placed that
      penetrated the sinus and/or nasal cavities. The penetrating portion of the
      implant was covered with autogenous particulate bone harvested from the lateral
      aspect of the ipsilateral sinus. In group 3, 39 patients had 152 implants fixed
      to autogenous mandibular bone grafts placed either in the antral and/or nasal
      floors and/or as an onlay over the residual alveolar ridge. The age range of the
      patients was 15 to 76 years, with a mean of 56 years. Follow-up periods ranged
      from 12 to 58 months, with a mean of 26 months. Of the 291 implants installed, 19
      have been lost. The importance of considering different treatment strategies when
      reconstructing the edentulous maxilla is discussed.

PMID- 8308619
TI  - The anxiolytic effects of intravenous sedation using midazolam alone or in
      multiple drug techniques.
AB  - This study examines four drug combinations (midazolam, midazolam-midazolam,
      fentanyl-midazolam, and fentanyl-midazolam-methohexital) in a placebo-controlled
      double-blind clinical trial of intravenous sedation. It tests the hypothesis that
      there is no difference between the anxiolytic effect of the four combinations
      when compared with a saline placebo. Subjects were 207 mildly anxious young
      adults having their third molars removed. Cognitive measures of anxiety increased
      from preoperative levels in the placebo and both midazolam groups (P < .05). The
      anxiety response remained the same in the fentanyl-midazolam and fentanyl
      midazolam-methohexital groups (P > .05). The level of successful anxiolysis
      ranged from 24% in the placebo group to 74% in the barbiturate group. Using the
      log likelihood method, comparisons suggest that the drug groups (from midazolam
      alone to the methohexital combination) have increasingly positive anxiolytic
      effects even when controlling for the effects of dental fear and intraoperative
      pain. The fentanyl-midazolam group is 8.1 and the methohexital group is 9.0 times
      more likely to have had a favorable outcome than the placebo group. Additional
      analyses of behavioral measures of anxiety yielded parallel results. Global
      evaluations after surgery were related to the success of anxiolysis for subjects
      in the active drug conditions (P < .05).

PMID- 8308620
TI  - Rigid fixation of mandibular fractures: does operator experience reduce
      complications?
AB  - Rigid internal fixation (RIF) is a frequently used method of reduction and
      immobilization of mandibular fractures. It has been postulated that the
      unexpectedly high complication rates reported in early studies of RIF were
      related to operator inexperience. The objective of this study was to determine if
      increased operator experience with RIF would result in a lower complication rate.
      Two 24-month patient care periods, separated by an intervening 12 months to avoid
      overlap, were evaluated retrospectively. Group 1 (n = 69 patients) represented
      the early experience and group 2 (n = 76 patients) the more recent data. The
      results of the study demonstrate a downward trend in the complication rate as
      surgeon experience increased. This improvement, however, was not statistically
      significant, and other factors may play a more important role in reducing
      complications.

PMID- 8308621
TI  - Complications of miniplate osteosynthesis for mandibular fractures.
AB  - Postoperative complications of delayed osteosynthesis with stainless steel
      miniplates were examined in 110 patients with mandibular fractures. The
      miniplates were removed in 91 of the patients, even if symptom-free, once
      sufficient bony union was obtained, and the healing conditions and the
      surrounding tissues were examined. Malocclusion, exposure of miniplates, delayed
      union, and infection were observed in 3.6%, 3.6%, 1.8%, and 1.0% of the patients,
      respectively. The complication rates were within acceptable limits even when
      treatment was performed later than 24 hours after injury. The healing conditions
      and the surrounding tissues did not show any serious problems. Thus, at least in
      short-term retention, stainless steel miniplates seem to be effective and
      suitable for osteosynthesis of mandibular fractures.

PMID- 8308622
TI  - Mandibular fractures in infants: review of the literature and report of seven
      cases.
AB  - Mandibular fractures in infants are rare. During the last 50 years, only 13 cases
      have been recorded in the literature. In this study seven cases of mandibular
      fractures in infants treated within a period of 3 years are reported. The male-to
      female ratio was 6:1. All fractures were caused by short falls, and in all cases
      the symphysis region was the injured site. The treatment approach was
      conservative, without any active intervention. The results were satisfactory;
      perfect alignment of the fractured bone segments was achieved in all cases.

PMID- 8308623
TI  - Comparison of the resistance of miniplates and microplates to various in vitro
      forces.
AB  - A comparison of the Luhr Mini System (Howmedica, Inc, Rutherford, NJ) and the
      Luhr Micro System (Howmedica, Inc) was undertaken to determine resistance to
      various forces using a biomechanical model. Miniplates and microplates were first
      tested to determine their resistance to forces of displacement on flat bend, edge
      bend, tension, and compression generated by a materials testing system machine.
      Then, miniplates and microplates were attached to fresh porcine ribs, fixed to a
      custom-made jig, and subjected to the same forces of displacement. The load was
      applied to the bone plate to permanent deformation in all tests. The mini and
      microplate systems resisted 14.50 and 1.14 kg, respectively, on edgewise bending,
      2.65 and 1.10 kg, respectively, on flat bending, 92.03 and 16.44 kg,
      respectively, on tension, and 127.9 and 27.02 kg, respectively, on compression.
      The mini and microsystem biomechanical model resisted 1.89 and 0.94 kg,
      respectively, on edgewise bending, 5.20 and 0.85 kg, respectively, on flat
      bending, 37.60 and 15.72 kg, respectively, on tension, and 53.55 and 16.0 kg,
      respectively, on compression. The results suggest that the Luhr Mini Fixation
      System provides a significant amount of resistance to tensile and compressive
      forces, but is weakest when large forces are applied at 90 degrees to the flat
      portion of the plate. The system showed decreased force resistance in the
      biomechanical model except on flat bending. The Luhr Micro Fixation System has
      significantly less resistance to deformation, but shows no decrease in ability to
      resist forces of displacement in the biomechanical model.

PMID- 8308624
TI  - Repair of temporomandibular joint disc perforation using a synovial membrane flap
      in Macaca fascicularis monkeys: light and electron microscopy studies.
AB  - Previous studies have demonstrated that experimentally produced perforations in
      the discs of Macaca fascicularis monkeys lead to osteoarthrosis. Synovial
      membrane hyperplasia also was demonstrated in monkey and human joints with disc
      perforations. The hypothesis was advanced that a synovial flap obtained from
      within the affected joint would be the most appropriate tissue to repair chronic
      disc perforation. To test this hypothesis, four adult M fascicularis monkeys were
      anesthetized and 4- to 6-mm perforations were made in the posterolateral aspects
      of the avascular discs bilaterally. The wounds were sutured leaving the
      perforations open, and the animals were fed their normal diet. After 4 weeks, one
      joint in each monkey was reopened and a repair was performed using a double
      layered flap from the synovial lining of the superior and inferior recesses. Four
      weeks after repair, the animals were killed and the temporomandibular joints
      (TMJs) were removed en bloc and decalcified. The joints were sectioned into
      lateral, middle, and medial sections and were photographed using a
      stereomicroscope and then processed for light and electron microscopy. The same
      processing was done to four intact joints that were used as controls. Eight weeks
      following perforation, the joint components showed degenerative changes
      consistent with osteoarthritis. Close to the perforations the disc showed loss of
      collagen, vacuolation of extracellular matrix, accumulation of dense proteoglycan
      like material, and the appearance within the disc of type A or macrophage-like
      cells of the synovium. The discal tissue away from the perforation showed high
      cellularity and vascularity. The temporal and condylar surfaces showed
      denudation, fibrillation, osteophytes, and chondrocytic clustering, all
      characteristics of osteoarthrosis. The surgically repaired discs were intact and
      the articular surfaces showed no degenerative changes. Discal collagen was
      restored and appearance of myofibroblasts and elastogenesis were a consistent
      feature of the repaired disc. The vascularity of the condylar cartilage of the
      repaired joints appeared similar to that of embryonic cartilage. The
      reversibility of the degenerative alterations following discal repair in this
      experimental model should provide the basis for a rational and useful method for
      surgical repair of TMJ disc perforation using intraarticular synovial tissue.

PMID- 8308625
TI  - A comparison of the form and function of the human, monkey, and goat
      temporomandibular joint.
AB  - The anatomic form and function of the human temporomandibular joint is compared
      with the monkey (Macaca and Papio) and goat joint. The findings indicate that the
      joint of the goat seems to be superior to the joint of Macaca and Papio as a
      research model.

PMID- 8308626
TI  - Diagnostic accuracy of the ultrathin arthroscope for temporomandibular joint
      osteoarthrosis: comparison of arthroscopic and histologic findings in a sheep
      model.
AB  - The diagnostic accuracy of the ultrathin arthroscope was evaluated by examination
      of the superior joint space of the left temporomandibular joint in 20 sheep. At
      the time of induction of osteoarthrosis all joints were found to be normal. Six
      months later the arthroscopic examination was repeated and the results compared
      with the histologic examination. Similar findings were seen in 11 joints (55%),
      with arthroscopic overdiagnosis in two (10%) and underdiagnosis in seven (35%).
      Eight of 16 (50%) disc perforations were found. It was concluded that
      underdiagnosis occurred because the whole joint space cannot be examined
      arthroscopically and fibrillated tissue masks bone exposure.

PMID- 8308627
TI  - Use of distraction osteogenesis for maxillary advancement: preliminary results.
AB  - In this pilot study, the principle of distraction osteogenesis to advance the
      anterior maxilla of the dog was used. After an anterior maxillary osteotomy, the
      anterior segment was advanced 10 mm in 10 days. Soft and hard tissue formation
      resulted in complete healing across the distraction gap without a soft tissue
      defect.

PMID- 8308628
TI  - Current concepts in the surgical management of temporomandibular joint disorders.
AB  - A thorough understanding of the structure and function of diarthrodial joints is
      necessary for clinicians who treat individuals with temporomandibular disorders.
      Surgical procedures must be based on principles designed to restore and preserve
      joint physiology. The surgical management of patients with temporomandibular
      joint disorders not only requires adherence to surgical principles that make
      sense from a physiologic basis, but also an understanding of the disease process
      and continued nonsurgical management that is aimed at reducing or eliminating
      factors which perpetuate joint overloading.

PMID- 8308629
TI  - Painful preauricular mass.

PMID- 8308630
TI  - A case of extensive subperiosteal spread of squamous cell carcinoma in the
      mandible.

PMID- 8308631
TI  - Fracture of radius 1 year after procurement of osteocutaneous flap.

PMID- 8308632
TI  - Cytomegaloviral infection of the mandible in acquired immunodeficiency syndrome.

PMID- 8308633
TI  - Monophasic spindle cell synovial sarcoma of the head and neck: report of two
      cases an review of the literature.

PMID- 8308634
TI  - Severe retroperitoneal hemorrhage complicating anterior iliac bone graft
      acquisition.

PMID- 8308635
TI  - Orofacial granulomatosis: report of a case with decreased CD4/CD8 ratio.

PMID- 8308636
TI  - Immunohistochemical analysis of a case of intraoral nodular fasciitis.

PMID- 8308637
TI  - A combined Le Fort I and bilateral zygomatic osteotomy for management of midface
      and maxillary deficiency.

PMID- 8308638
TI  - Modification of the sinus lift procedure for septa in the maxillary antrum.

PMID- 8308639
TI  - Reduction of manpower: a solution to the problem of busyness.

PMID- 8308640
TI  - Reduction of manpower: a solution to the problem of busyness.

PMID- 8308641
TI  - Reduction of manpower: a solution to the problem of busyness.

PMID- 8308642
TI  - A new species of Heterorhabditis from the Hawaiian Islands.
AB  - A new species of nematode of the genus Heterorhabditis (Nemata:
      Heterorhabditidae) was found during a survey of the soil entomopathogenic
      nematode fauna of the Hawaiian Islands. Heterorhabditis hawaiiensis sp. n. can be
      separated from all other species of Heterorhabditis by the length of the
      infective juvenile and the morphological characters of the spicules,
      gubernaculum, and bursa. Random amplified polymorphic DNA (RAPD) fragment
      analysis showed that this species also has a distinct genetic pattern in RAPD
      bands relative to the other 6 species or isolates of Heterorhabditis that were
      compared.

PMID- 8308643
TI  - New morphological characters for identifying individual specimens of Haemonchus
      spp. (Nematoda: Trichostrongyloidea) and a key to species in ruminants of North
      America.
AB  - The large stomach worms Haemonchus contortus, Haemonchus placei, and Haemonchus
      similis are important pathogens of cattle and sheep. This paper describes
      characteristics of surface cuticular ridges (synlophe), which for the first time
      provide morphological criteria for identifying individual adult specimens of
      either sex. The diagnostic patterns of the synlophe on the anterior half of
      specimens can be observed at 400x in temporary mounts on glass slides. The
      synlophe can be studied in cleared preserved specimens or in living or freshly
      thawed frozen specimens mounted in water. The synlophe of H. contortus has 30
      ridges in the region of the posterior half of the esophagus, 4 fewer than H.
      placei and H. similis. The 4 extra ridges of H. placei and H. similis are
      consistently located bilaterally to the 3 ventralmost and the 3 dorsalmost
      ridges. The 4 extra ridges of H. similis extend to the end of the synlophe
      posterior to midbody, but in H. placei they extend posteriorly only to the end of
      the anterior quarter of the nematode. A key is included to the 3 species of
      Haemonchus parasitic in domestic sheep and cattle using characteristics of
      spicules, female reproductive system, female tail, and the synlophe.

PMID- 8308644
TI  - Trichospirura amphibiophila n. sp. (Nematoda: Rhabdochonidae) in the frog
      Eleutherodactylus martinicensis from La Desirade, French Antilles.
AB  - Trichospirura amphibiophila n. sp. (Nematoda) is described from the abdominal
      cavity (encapsulated near the liver) of the frog Eleutherodactylus martinicensis
      (Anura: Leptodactylidae) from the island of La Desirade in the French Antilles.
      It is characterized by the length of its spicules (459 microns and 90 microns)
      and their length ratio (1:5), by the presence of deirids and 7 pairs of caudal
      papillae in the male (2 preanal and 5 postanal), and by the site of localization
      (abdominal cavity) in the host. Trichospirura amphibiophila is the first known
      species of the genus parasitizing amphibians.

PMID- 8308645
TI  - Interaction of mebendazole with tubulin from body wall muscle, intestine, and
      reproductive system of Ascaris suum.
AB  - The binding of tritiated mebendazole, a benzimidazole anthelmintic, to tubulin
      derived from intestine, body wall muscle, and reproductive system of adult
      Ascaris suum was examined and compared. Mebendazole binding was resolved into
      specific and nonspecific binding and the binding affinity (Ka) and maximum
      binding at infinite ligand concentration (Bmax) determined. Electron microscopy
      was performed to assess the tubulin in various tissues of A. suum quantitatively
      by observing the presence of microtubules. Total binding was highest in intestine
      followed by body wall muscle. It was least in the reproductive system. The
      intestine demonstrated greater specific binding per milligram of protein than the
      body wall muscle. However, in the reproductive system extract, high affinity
      binding was not detected. After correction for nonspecific binding of ligand, the
      results indicated that the Bmax of mebendazole for the tubulin of A. suum
      intestine was about 3-fold higher than for that of body wall muscle. The Ka of
      mebendazole for intestinal tubulin was similar to that for body wall muscle.
      Electron microscopy of A. suum tissues demonstrated that the tubulin content
      decreased from the intestine through the body wall muscle to the reproductive
      system. Differences in tubulin content from different tissues may determine the
      selective sensitivity of these tissues to benzimidazole attack.

PMID- 8308646
TI  - Ultrastructural comparison of extracellular and intracellular encapsulation of
      Brugia malayi in Anopheles quadrimaculatus.
AB  - Ultrastructural aspects of extracellular humoral encapsulation of microfilariae
      of Brugia malayi in the hemocoel of Anopheles quadrimaculatus were compared with
      those of intracellular encapsulation of first-stage larvae (L1) of the same
      parasite species, in the thoracic muscle cells of the same species of mosquito.
      The results showed that extracellular humoral encapsulation of microfilarial
      sheaths, and sheathed and exsheathed microfilariae, in the hemocoel of mosquitoes
      occurs around the parasite within the first 6 hr postingestion, apparently
      without initial participation of hemocytes. Hemocytes and their remnants were
      observed near the parasite during the first 6 hr postingestion. Within the next
      24 hr, hemocytes attach to the initial humoral capsule. By contrast,
      intracellular encapsulation of L1S is initiated by the accumulation of a dense
      cytoplasmic layer derived from the infected thoracic muscle cell. Melanin
      deposits accumulate in this layer adjacent to the parasite cuticle, again without
      visible participation of hemocytes.

PMID- 8308647
TI  - Echinococcus granulosus (Taeniidae) and autochthonous echinococcosis in a North
      American horse.
AB  - We report the first documented case of autochthonous echinococcosis in a horse of
      North American origin. Three fully mature and viable unilocular hydatid cysts of
      Echinococcus granulosus (Batsch, 1786) were an incidental finding at necropsy in
      the liver of a 14-yr-old gelding thoroughbred that had been foaled in Virginia
      and raised in Maryland. Protoscolices were armed with 2 rows of 28-37 rostellar
      hooks; small hooks measured 23-30 microns; large hooks measured 26-33 microns.
      Morphologically, these were compatible with rostellar armature considered typical
      for the equine strain of E. granulosus currently known primarily from the United
      Kingdom. This horse had a history of fox hunting, and huntsman at some premises
      in the region are known to feed uncooked viscera from horse carcasses to their
      dogs. These factors would support maintenance of infection by E. granulosus in
      equine hosts. The putative introduction and establishment of the equine strain of
      E. granulosus and recognition of endemic equine hydatid disease in the eastern
      U.S.A. warrants monitoring and additional investigation.

PMID- 8308649
TI  - Enhancement of virulence of Naegleria fowleri by growth in Vero-cell cultures.
AB  - The virulence of Naegleria fowleri for mice decreases with prolonged maintenance
      in axenic culture. Would the virulence be affected if amebas were grown in
      African green-monkey kidney (Vero)-cell cultures rather than in axenic culture?
      The weakly virulent LEE strain of N. fowleri was cultivated with Vero cells for 6
      mo and tested in mice for changes in virulence. We found that continuous growth
      in Vero-cell cultures enhanced the virulence of the LEE strain and we propose
      that, as an alternative to serial passage in mice, the virulence of weakly
      virulent strains of N. fowleri may be enhanced by maintenance in Vero-cell
      cultures.

PMID- 8308648
TI  - 5-Hydroxytryptamine (serotonin)-immunoreactivity in the nervous system of
      Mesocestoides corti tetrathyridia (Cestoda: Cyclophyllidea).
AB  - An indirect immunocytochemical technique has been interfaced with confocal
      scanning laser microscopy to investigate the occurrence and distribution of
      serotoninergic (5-HT) nerve elements in Mesocestoides corti tetrathyridia. Cell
      bodies and nerve fibers immunoreactive to 5-HT were found concentrated in the
      innervation around the 4 suckers and associated commissures and in the 5 pairs of
      longitudinal nerve cords and their cross-connectives. Immunoreactivity was
      evident also in the extensive, peripheral network of fine fibers of the
      subtegumental region and in the plexus of varicose fibers that innervate the
      muscle in each of the suckers. In dividing stages of the tetrathyridium, the
      immunoreactive lateral nerve cords of adjoining progeny were in continuity around
      the base of the division cleft.

PMID- 8308650
TI  - Identification of Trichinella isolates from naturally infected stray dogs in
      Egypt.
AB  - Larvae of Trichinella species recovered from the diaphragms of 2 stray dogs
      killed during a governmental antirabies campaign in Cairo, Egypt, were fed to
      white mice for production of adult worms and larvae for morphological and
      isoenzyme studies. Comparisons were made with reference species of Trichinella
      spiralis, Trichinella nelsoni, Trichinella nativa, and Trichinella
      pseudospiralis. Results indicated that the 2 Trichinella specimens from the dogs
      were morphologically and biochemically identical with T. spiralis.

PMID- 8308651
TI  - Brevimulticaecum sp. larvae (Nematoda: Anisakidae) from the frog Hyla minuta
      Peters in Trinidad.
AB  - Enscapsulated third-stage nematode larvae collected from the abdominal cavity of
      the Trinidadian hylid frog Hyla minuta are referred to the rare anisakid genus
      Brevimulticaecum. These are the first specimens of Brevimulticaecum from a
      tropical frog, and their presence may reflect the importance of amphibians as
      intermediate or paratenic hosts of reptilian parasites.

PMID- 8308652
TI  - Presbytis entellus, a new experimental host for Plasmodium fragile.
AB  - The course of blood-induced Plasmodium fragile infection in 3 simian hosts,
      Macaca radiata (bonnet monkey), Macaca mulatta (rhesus monkey), and Presbytis
      entellus (Indian langur), was studied. The infection in 8 bonnet monkeys was very
      mild and nonfatal. In M. mulatta, P. fragile produced acute initial infection
      followed by anemia and death in 3 of 6 monkeys. The parasite has a relatively
      high level of virulence for P. entellus, a new experimental host for P. fragile,
      in which peak parasitemia ranging between 15 and 75% was recorded, and the
      infection was uniformly fatal. Plasmodium fragile infection in P. entellus can
      serve as an ideal biological counterpart to human Plasmodium falciparum.

PMID- 8308653
TI  - Prolonged exposure of Plasmodium falciparum to ciprofloxacin increases anti
      malarial activity.
AB  - The minimum inhibitory concentration (MIC) of ciprofloxacin was determined for 2
      isolates of Plasmodium falciparum at 48, 96, and 144 hr. The MIC decreased from
      mean values of 28.1 micrograms/ml for the FC isolate and 27.2 micrograms/ml for
      the K1 isolate at 48 hr to 2.8 micrograms/ml and 4.4 micrograms/ml, respectively,
      at 96 hr. Concentrations of 0.1-1.0 micrograms/ml were effective in suppressing
      parasite growth over 144 hr of incubation. These findings indicate that the
      multiplication of malaria parasites can be inhibited by clinically achievable
      concentrations of ciprofloxacin provided that exposure to the drug is prolonged
      over several asexual erythrocytic cycles. They also raise the possibility that
      this antibiotic could be used eventually, in combination with a rapidly acting
      but noncurative drug regimen, to treat patients with refractory falciparum
      infections.

PMID- 8308654
TI  - The food resource of adult Heligmosomoides polygyrus in the small intestine.
AB  - The aim of this study was to identify the food resources of Heligmosomoides
      polygyrus, a gastrointestinal nematode of mice. Gastrointestinal nematodes obtain
      food from 1 of 3 compartments: host ingesta, blood, or intestinal tissue. A
      method was developed to label these compartments differentially in the living
      host using 2 fluorescent marker dyes and to record in situ feeding activity of
      the parasite. Fluoresbrite is a yellow-green fluorescent dye bound to small
      diameter beads that are membrane impermeable. Thus, it is restricted to the
      bloodstream when introduced there, or it remains in the ingesta when fed to the
      host. Rhodamine B, a red fluorescent dye, is membrane permeable and stains tissue
      cytoplasm. These dyes were fed to or injected into the bloodstream of the host.
      Following treatment, the worms were removed, and the contents of the worm
      intestines were examined by fluorescent microscopy. Worm intestinal contents only
      fluoresced with rhodamine B dye. These results suggest that H. polygyrus adults
      feed on tissue in the living host and not on host ingesta or blood.

PMID- 8308655
TI  - In vitro cultivation of cells from larval Schistosoma mansoni.
AB  - With the intent of providing a useful tool for studies on the cellular and
      molecular biology of Schistosoma mansoni, we have attempted to establish
      indefinitely proliferating cell lines. Primary (mother) sporocysts have served as
      sources of tissue fragments for initiation of primary cultures in complex media
      containing fetal bovine serum. Viability is maintained for several months, during
      which time there is differential survival of individual cell types. Cells that
      ultrastructurally resemble germinal cells are among the most persistent.
      Contractile responsiveness to serotonin and flagellar movement of flame cells are
      sustained for several weeks. Exposure to epidermal growth factor failed to induce
      tyrosine phosphorylation as detectable by western blot analysis. Incorporation of
      5-bromo-2'-deoxyuridine into nucleic acid has been used as an indicator of the
      merit of experimental variables tested for their growth-promoting potential.
      Continuous proliferation remains an elusive goal, but coculture with host snail
      ganglia has yielded promising results. These primary cultures can be used to
      obtain useful information on parasite physiology. In light of our results, and of
      the varied lines of investigation that would be facilitated by such tools,
      further efforts to immortalize cell lines are warranted.

PMID- 8308656
TI  - Comparative studies on Giardia lamblia encystation in vitro and in vivo.
AB  - The distribution of Giardia lamblia (WB strain) trophozoites, encysting
      trophozoites (i.e., trophozoites bearing encystation-specific vesicles [ESV]) and
      cysts in the intestines of gerbils was examined over a period of 30 days.
      Trophozoites and encysting trophozoites were found in 3 equal length sections of
      the small intestine and in much lower numbers in the colon. Cysts were
      consistently found only in the second and third sections of the small intestine
      and in the colon. In a comparative encystation study in vitro, 4 populations of
      WB strain trophozoites were used: WB (uncloned), D1 (a recent clone of WB), WB-C6
      (a 1983 clone of WB), and V1 (a recent subclone of WB-C6). The WB-C6 and V1
      populations produced significantly higher numbers of encysting trophozoites and
      cysts in vitro than did the WB and D1 populations. In addition, WB-C6 and V1
      produced significantly more water-resistant cysts in vitro than WB and D1.
      However, there was no difference in fecal cyst excretion in gerbils infected with
      the 4 populations of WB-derived trophozoites. One cycle of
      encystation/excystation in gerbils increased the in vitro encystation of WB and
      D1 populations but decreased in vitro encystation of C6 and V1. We could detect
      no difference in protein profiles or isoenzyme patterns between these 4
      populations of cells before or after passage in gerbils.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8308657
TI  - Proteolytic enzymes of Pomphorhynchus laevis and in three other acanthocephalan
      species.
AB  - Cystacanths and adults of the acanthocephalan Pomphorhynchus laevis were found to
      release proteolytic enzymes during in vitro culture. Culture media in which
      cystacanths had been kept contained a trypsinlike collagenolytic proteinase
      exhibiting a molecular mass of 29 kDa on gelatin substrate gel electrophoresis
      and a pH optimum at pH 9.0. Samples of adults possessed a trypsinlike
      collagenolytic proteinase with a molecular mass of 26 kDa and showed a pH optimum
      at 9.0. Leucine aminopeptidase activity was also present in culture media of
      adults. An apparent molecular mass of 92 kDa and a pH optimum at pH 8.5 were
      determined for this proteolytic enzyme. It was concluded that the trypsinlike
      proteinases of both stages were necessary for the complete and quick perforation
      of the fishes' intestinal wall, whereas the leucine aminopeptidase seemed to have
      a nutritional function in the terminal stages of protein hydrolysis at the
      surface of the worm's body wall. Cystacanths of 3 other species of fish
      parasitizing Acanthocephala (Acanthocephalus anguillae, Acanthocephalus lucii,
      Paratenuisentis ambiguus) did not show any histolytic activity.

PMID- 8308658
TI  - The interaction of Lactobacillus acidophilus and Trichomonas vaginalis in vitro.
AB  - Recent work with a mouse model of Trichomonas vaginalis infection indicated that
      estrogenized BALB/c mice that were preinfected with Lactobacillus acidophilus
      showed a greater duration of T. vaginalis infection as compared to a control
      group of mice that were not treated with L. acidophilus. To examine the
      interaction between T. vaginalis and L. acidophilus further we performed in vitro
      competitive growth assays between the 2 species. Although the addition of L.
      acidophilus to the T. vaginalis cultures slowed the growth of the protozoa, the
      added bacteria did not increase trichomonad death. However, T. vaginalis had a
      deleterious effect on L. acidophilus growth in combined cultures when compared to
      matched controls. Using an initial inoculum of 10(5)/ml, at 40 hr the control L.
      acidophilus concentrations had grown to 1.3 x 10(7)/ml. However, in combined
      culture with T. vaginalis, L. acidophilus concentrations at 40 hr had fallen to
      7.8 x 10(5)/ml and 6.1 x 10(4)/ml for the 10:1 (T. vaginalis at 10(4)) and 1:1
      (T. vaginalis at 10(5) test ratios, respectively (P < 0.01). This demonstrates
      that T. vaginalis can cause the concentration of L. acidophilus to fall in vitro
      and may explain why the concentration of L. acidophilus in the vagina falls in
      trichomoniasis.

PMID- 8308659
TI  - Periparturient rise in the excretion of Giardia sp. cysts and Cryptosporidium
      parvum oocysts as a source of infection for lambs.
AB  - The possibility of a periparturient rise (PPR) in the excretion of
      Cryptosporidium parvum oocysts and Giardia duodenalis-type cysts and its
      implications in the epidemiology of these 2 pathogens were investigated. Fecal
      samples were taken from 32 lambing ewes every 2 wk from 4 wk before lambing until
      8 wk after the start of lambing. Samples from both ewes and lambs were examined
      with a quantitative immunofluorescence assay. Excretion of Giardia sp. cysts by
      ewes increased at 2 wk prepartum, peaked at zero and 4 wk postpartum, and
      returned to low levels at 6 and 8 wk postpartum. Some ewes also excreted C.
      parvum oocysts at the start of lambing. Excretion rates and intensities of
      Giardia sp. cysts by lambs were high, whereas those of C. parvum oocyst excretion
      were light. The PPR in excretion of Giardia sp. cysts by ewes was considered to
      be the major source of giardiasis for lambs. Excretion of C. parvum oocysts by
      ewes at parturition also played a role in initiating cryptosporidiosis in lambs.

PMID- 8308660
TI  - An ELISA for detecting anti-Plasmodium spp. antibodies in African black-footed
      penguins (Spheniscus demersus).
AB  - An enzyme-linked immunosorbent assay (ELISA) utilizing 3 Plasmodium falciparum
      antigens, R32tet32, P.F.R27, and crude red blood cell extract, was developed for
      the detection of circulating anti-Plasmodium relictum or anti-Plasmodium
      elongatum antibodies in sera from naturally infected adult African black-footed
      penguins (Spheniscus demersus) at The Baltimore Zoo, Maryland. A concentration of
      2.0 micrograms/ml of each antigen was optimal in terms of specificity,
      sensitivity, and test speed. It was possible to detect anti-Plasmodium spp.
      antibodies at a dilution of 10(-4.11). Low absorbance values (less than 0.050) of
      nonspecific background were observed. The binding efficacy of anti-penguin IgG
      coupled to alkaline phosphatase to antibodies in the penguin sera was
      significantly higher than the binding efficacy of anti-chicken IgG. All penguins,
      bled in the winter time, in controlled mosquito-free conditions had anti
      Plasmodium spp. antibodies reactive with P. falciparum antigens. The penguins
      showed age-dependent variation in antibody levels. There was a decrease in
      antibody titration units that was significantly correlated with the number of
      outdoor exposure years experienced by the birds, despite the season-comparable
      epizootiologic conditions in their summer open-air habitat. We concluded that the
      decrease of anti-malarial antibodies could be explained by an antibody-mediated
      equilibrium of immunity in naturally immunized birds harboring endothelial-stage
      parasites. The ELISA described is sensitive, and it requires a minimal amount of
      equipment to collect the blood samples. The assay can be used for detecting and
      monitoring levels of anti-Plasmodium spp. antibodies in selected groups of
      penguins.

PMID- 8308661
TI  - Feline serum antibody responses to Toxoplasma gondii and characterization of
      target antigens.
AB  - The Toxoplasma gondii-specific target antigens for feline immunoglobulin M (IgM)
      and immunoglobulin G (IgG) immune responses were studied longitudinally using
      western blot immunoassay in 8 cats experimentally inoculated with T. gondii
      strain ME49. Multiple antigens were recognized by IgM and IgG during the course
      of infection. Dense bands were associated with 12 antigens in the IgM western
      blot immunoassay and 30 antigens in the IgG western blot immunoassay.
      Immunoglobulin M responses were maximal on week 4 postinoculation (PI) and were
      greatly diminished by week 20 PI. Immunoglobulin G responses were maximal on week
      12 PI. On week 20 PI, the 19-kDa (6/8 samples), 26-kDa (8/8 samples), 28-kDa (8/8
      samples), 31-kDa (7/8 samples), 35-kDa (6/8 samples), 51-kDa (6/8 samples), 55
      kDa (7/8 samples), and 65-kDa (7/8 samples) antigens were recognized most
      commonly in the IgG western blot immunoassay. When the western blot immunoassay
      results were compared to enzyme-linked immunosorbent assay (ELISA) results, there
      was no clear advantage to the development of IgM-ELISA, IgG-ELISA, IgM western
      blot immunoassay, or IgG western blot immunoassay using a single antigen instead
      of multiple antigens as the detection system for the diagnosis of recent
      infection.

PMID- 8308662
TI  - Absence of acquired resistance to nymphal Ixodes ricinus ticks in BALB/c mice
      developing cutaneous reactions.
AB  - BALB/c mice underwent 3 successive infestations with 15 Ixodes ricinus nymphs. No
      resistance was acquired as assessed by evaluating tick attachment, duration of
      blood meal, weights of engorged nymphs, and molting success. However, the hosts
      developed cutaneous immediate- and delayed-type hypersensitivity reactions when
      reinfested. Histological examination of tick attachment sites showed that
      inflammatory cells consisting of neutrophils, eosinophils, and mononuclear cells
      (lymphocytes and monocytes) infiltrated the skin more intensively during
      reinfestations. The number of intact mast cells did not vary between successive
      infestations, whereas the number of degranulated mast cells increased in the
      early stages of reinfestations. Basophils, which represent 12% of total
      infiltrating cells, were only observed and quantified in the skin of reinfested
      mice using transmission electron microscopy (TEM). Degranulating eosinophils were
      also observed by use of TEM.

PMID- 8308663
TI  - Effects of transmission-blocking immunity on Plasmodium vivax infections in
      Anopheles albimanus populations.
AB  - Two colonized populations of Anopheles albimanus isolated from the Suchiate
      region, Chiapas State, Mexico, were compared for their susceptibility to
      coindigenous Plasmodium vivax. Groups of mosquitoes were fed in vitro with either
      autologous donor blood or the same blood cells substituted with serum negative
      for anti-gametocyte antibody. Significant differences in susceptibility between
      the 2 colonies were encountered if the autologous blood from a patient was fed to
      mosquitoes: mean infection rates of AnA2-positive groups was double that in AnA1
      mosquitoes. Consistent for both colonies, only 23.6% of samples positive from
      malaria-negative serum-substituted blood were infected with an autologous blood
      feed. Vector competence in these mosquito populations was partially linked to the
      human populations's immune response to the parasite.

PMID- 8308664
TI  - An experimental model of the production of metastases in murine cutaneous
      leishmaniasis.
AB  - An experimental investigation into the influence of artificially induced trauma
      in the production of leishmanial metastatic lesions and into the possible role
      played by Leishmania-reactive T cell populations in the metastatic process was
      carried out. Trauma was induced by incising a small cut into the shaved rump of
      Leishmania amazonensis-infected BALB/c mice. Ten days after the trauma, mice were
      killed to quantify the parasite load in the traumatic lesion or in the equivalent
      area in nontraumatized mice, by limiting dilution analysis. Results demonstrated
      that metastatic lesions occurred earlier in traumatized animals and that
      parasites could be detected sooner in traumatic lesions than in equivalent areas
      in nontraumatized mice. When lymph node cells from L. amazonensis antigen
      immunized BALB/c mice were adoptively transferred intravenously to L. amazonensis
      infected syngeneic mice, the parasite load in the metastatic lesions was greater
      in the animals that received La Ag-reactive T cells than in the controls. When
      CD4(+)- or CD8(+)-depleted T cell populations from La Ag-immunized mice were
      adoptively transferred to infected traumatized or nontraumatized animals, we
      observed that the metastatic lesions in CD4(+)-inoculated animals had a greater
      number of parasites than the lesions in mice from all other groups. Thus, a new
      and reliable mouse model for studying the mechanisms involved in leishmanial
      metastasis is described.

PMID- 8308665
TI  - Estimation of lungs' hypoplasia on postoperative chest x-rays in congenital
      diaphragmatic hernia.
AB  - Since we stopped inserting ipsilateral underwater chest drains after surgical
      reduction of the herniated contents in congenital diaphragmatic hernia, both
      lungs are allowed to expand at their own pace, making it possible to estimate
      their degree of hypoplasia on postoperative chest x-rays. Thirty-nine consecutive
      series of postoperative chest x-rays were examined by an independent reviewer in
      a blind manner and classified into three groups: none to mild pulmonary
      hypoplasia (group I, 10 cases); moderate to severe (group II, 20 cases); and very
      severe hypoplasia (group III, 9 cases). Correlations were done among groups and
      available anatomical and clinical data. Eight patients out of 9 survived in spite
      of very severe hypoplasia on postoperative chest x-rays, suggesting that indexes
      of severity may be misleading when they mistake pulmonary hypoplasia for the
      cause of death.

PMID- 8308666
TI  - A new method of treatment for pulmonary hypertension in congenital diaphragmatic
      hernia: experimental study in cats.
AB  - This research proposes a new treatment for pulmonary hypertension secondary to
      perivascular emphysema, the so-called air-block syndrome. Vibrations applied on
      the thorax can fraction air bubbles around the vessels into smaller ones,
      facilitating their redistribution and reabsorption, thus reducing the extrinsic
      compression on pulmonary vasculature. In cats, pulmonary lesions were obtained by
      continuous insufflation of air at 40 cm H2O for 2 minutes in a lower lobe of the
      lung. Vibrations applied on the thorax were produced with the same apparatus as
      used by physiotherapists to eliminate pulmonary secretions. Thirty-three cats
      were divided into three groups: lesions without treatment, lesions treated by
      vibrations, and controls. A catheter was inserted in the pulmonary artery for
      pulmonary artery pressure (PAP) measurements. One carotid was cannulated for
      arterial pressure and blood gases monitoring. Morphometric analysis of the lung
      had also to be carried out in all cases. Results showed a very significant
      decrease on pulmonary hypertension in the treated group after only 20 minutes of
      treatment by vibrations (P < .004). Results also confirmed the very strong
      relationship between PAP variations and perivascular emphysema found on
      postmortem examination (r2 = .64, P < .01). Extrinsic compression decreased from
      29% in the untreated group to 21% in the treated one (n = 10 pairs, P < .08).
      These data suggest that vibrations may be a new simple treatment for pulmonary
      hypertension, when perivascular emphysema is involved, and could be useful in
      congenital diaphragmatic hernia as well in other neonatal pathologies.

PMID- 8308667
TI  - Withholding and withdrawal of life support from surgical neonates with life
      threatening congenital anomalies.
AB  - We evaluated why and how life support was withheld or withdrawn in surgical
      neonates. During the study period, January 1988 through December 1991, 529
      neonates were admitted, 52 of whom died (10%). Twenty-eight deaths were due to
      the underlying disease. The other 24 patients died because treatment was withheld
      or withdrawn. In 15 of 24 (group A, mean stay 9.2 +/- 9.1 days) treatment was
      initially started but later withdrawn (13/15) because of the severity of
      congenital anomalies alone (7/12) or congenital anomalies associated with
      chromosomal anomalies (5/12). In 9 of 24 (group B, mean stay 20.3 +/- 17.3 days)
      treatment was withdrawn because of serious complications. In all cases often
      lengthy discussions have led the doctors and nurses together with the parents to
      chose unanimously for withdrawal of treatment. Mechanical ventilation was the
      intervention most frequently withdrawn (10/15 group A, 9/9 group B). Vasoactive
      and other drugs were withheld in 5 patients of group A. Sedatives and analgetics
      were administrated as supportive care permitting the child to die in a humane
      way, 17 in the lap of a parent and 7 in the lap of a nurse. We conclude that life
      sustaining care is withheld or withdrawn relatively frequently from patients at
      our ICU. Such decisions are ethical ones, taken in the light of professional and
      technical expertise. Evaluation of withholding or withdrawal of treatment is
      difficult but necessary to evolve appropriate decision-making procedures and to
      formulate humane standards of intensive care.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308668
TI  - The impact of spina bifida on the medical services of Newfoundland and Labrador.
AB  - This institution receives all live spina bifida patients from Newfoundland and
      Labrador. The aim of this study is to determine the outcome of these patients and
      the impact on the medical system. On a retrospective chart review, 274 patients
      born between 1967 and 1990 were studied. An analysis of the statistical variables
      showed that the incidence per 1,000 live births has remained stationary in
      Newfoundland and Labrador; there is a slight female predominance; 64% were born
      to young mothers and the peak incidence occurred in March, April, and May. A
      total of 179 patients of 254 who underwent surgery were alive and underwent
      rehabilitation programmes. Only 35% are wheelchair bound; the rest are
      ambulatory. One hundred sixty-one are of school age or older, 78 are in regular
      high school (3 dropouts), 36 are in special education, 6 graduated from high
      school, 4 are in university, 15 had no neurological deficit, 7 were lost in
      follow-up, 5 died, 9 had gross mental retardation, and 1 is the mother of three
      normal children. To attain these results these patients had multiple admissions
      and surgical procedures and the patients are seen twice a year in a
      rehabilitation and multidisciplinary clinic. From this study, the utilization of
      the medical services and impact on the community is great. However, the majority
      of these patients appear to attain a surprisingly high quality of life.

PMID- 8308669
TI  - Biliary tract complications in pediatric orthotopic liver transplantation.
AB  - Biliary tract complications are reported in 15% to 30% of orthotopic liver
      transplantations (OLTs). Since 1986, 53 OLTs were done in 48 children with a mean
      age and weight of 5.3 years and 18.9 kg, respectively. Twenty-seven
      transplantations (51%) were reduced liver grafts (RLG) and 26 (49%) were whole
      liver grafts (WLG). Since 1988, 70% of transplantations have been RLG.
      Choledochocholedochostomy (mean weight, 25 kg) with a T-tube (CC) or
      choledochojejunostomy (CJ) (mean weight, 14.5 kg) were done in 24 (45%) and 29
      (55%) cases, respectively. The overall mortality was 19% but none of the deaths
      were related to biliary problems. There were 13 biliary tract complications
      (24.5%) in 11 patients including 7 leaks, 5 obstructions, and 1 intrahepatic
      biloma. Leaks leading to bile peritonitis were managed with simple suture and
      drainage and were related to the T-tube (4), to the Roux-en-Y loop (2), and to
      the transection margin of a RLG (1). Obstruction was documented in 5 cases with
      none associated with hepatic artery thrombosis (HAT). Stenosis after CC
      reconstruction (2) required conversion to CJ. Two patients had revision of CJ
      because of kinking of the common bile duct after a left lateral segment graft and
      an anastomotic stricture 46 months after OLT. The last patient developed a
      vanishing bile duct syndrome 4 months posttransplant and is awaiting
      retransplantation. One patient had multiple episodes of cholangitis after HAT and
      was retransplanted. Neither the type of grafts (RLG 25.9% v WLG 23.1%) nor the
      type of biliary reconstruction (CC 25% v CJ 24%) influenced the rate of biliary
      complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308670
TI  - Idiopathic acute portal vein thrombosis: a case report.
AB  - There are few reported cases of acute portal vein thrombosis presenting as an
      acute abdomen in adolescent age group. Most published series concern chronic
      extrahepatic portal vein thrombosis. Acute portal vein thrombosis is rare, but
      can develop into serious complications. Hence, prompt diagnosis and
      heparinization can prevent the development of lethal complications such as venous
      gangrene of the bowel and portal hypertension.

PMID- 8308671
TI  - Thrombosis of the portal venous system after splenectomy for pediatric
      hematologic disease.
AB  - Splenic, portal, or mesenteric venous thrombosis after splenectomy for
      hematologic disease has not been reported in the pediatric literature. It is a
      rare complication associated with significant morbidity and mortality in adult
      reports. Between 1981 and 1991, 3 patients (13-year-old boy with hereditary
      elliptocytosis [HE], 13-year-old boy with thalassemia intermedia [TI], and 18
      year-old girl with idiopathic thrombocytopenic purpura [ITP]) presented with
      abdominal pain, nausea, with or without fever, at 4, 11, and 13 days
      postsplenectomy, respectively. Abdominal Doppler ultrasound (US) and/or computed
      tomography (CT) showed: (1) an intraluminal filling defect with partial
      obstruction to flow in the right branch of the portal vein with the remaining
      vessels patent (HE); (2) splenic vein thrombosis with complete occlusion of the
      main portal vein and proximal superior mesenteric vein (TI); and (3) complete
      thrombosis of the splenic vein, proximal superior mesenteric vein and portal vein
      (including central radicles), with retrogastric collateralization (ITP).
      Subsequent imaging showed either complete resolution of vascular obstruction on
      no treatment (patient 1), or portal venous cavernomatous transformation with
      hepatofugal flow after 6 months of systemic anticoagulation (patients 2 and 3),
      and all 3 patients are currently asymptomatic. Postoperative sonographic
      evaluation of a consecutive series of pediatric splenectomies for hematologic
      disease (n = 16), was performed at a median of 51 days (range, 3 to 124). This
      demonstrated one case of asymptomatic left portal venous thrombosis with
      subsequent recanalization in the absence of treatment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8308672
TI  - Histamine does not mediate mucosal permeability changes after subclinical
      intestinal ischemia-reperfusion injury.
AB  - Subclinical intestinal ischemia-reperfusion injury (IRI) increases mucosal
      permeability, and may be an important mechanism in the etiology of necrotizing
      enterocolitis. The current study was designed to assess the role of histamine in
      mediating this phenomenon. Six-week-old rats underwent 10-minute superior
      mesenteric artery occlusion (SMAO) or sham operation, and ileal mucosal
      permeability to 51Cr EDTA was measured 30 minutes after reperfusion. Rats were
      pretreated with intravenous saline, mepyramine (6 mg/kg), or ranitidine (5
      mg/kg). SMAO resulted in a significant increase in permeability compared to sham,
      which was not attenuated by either of the histamine antagonists. In a second
      experiment, mucosal permeability to 51Cr EDTA was measured in 6-week-old rats
      during aortic infusion of saline or histamine (0.5 mg/kg/min). There was no
      significant increase in permeability as a result of histamine infusion. In a
      third experiment, 6-week-old and 10-day-old rats underwent sham or 10-minute
      SMAO, and both portal vein and ileal tissue histamine levels were measured 30
      minutes after reperfusion. There was no significant difference between sham and
      SMAO with respect to portal vein histamine or tissue histamine at either age. IN
      CONCLUSION: (1) increased permeability was not blocked by either H1 or H2
      blockers; (2) histamine infusion did not increase permeability; and (3) SMAO did
      not increase portal vein or tissue histamine levels. These data suggest that
      histamine does not play a role in mediating the increase in permeability after
      subclinical IRI in this model.

PMID- 8308673
TI  - Vasoactive intestinal polypeptide causes relaxation of the pyloric sphincter in
      the rabbit.
AB  - Vasoactive intestinal peptide (VIP), which causes relaxation of gastrointestinal
      smooth muscle, has been found in high concentrations in the pylorus in many
      animal species, suggesting a prominent role for VIP in the control of pyloric
      sphincter function. We infused VIP into the gastric artery of 6 rabbits at rates
      from 12 to 1,200 ng/min and measured the intensity, duration, and frequency of
      spontaneous pyloric contractions with an intraluminal balloon and
      electromyography. VIP produced a dose-dependent reduction in the intensity (55%
      +/- 15% of baseline, P < .001) and the duration (29% +/- 25%, P < .001) of
      pyloric contraction. Maximal inhibition was observed at an infusion rate of 240
      ng/min. The frequency of contractions did not decrease significantly in response
      to VIP infusion. Neostigmine infusion increased the intensity of pyloric
      contraction in a dose-dependent manner in doses of 0.10, 0.15, and 0.25 mg (140%
      +/- 78%, 273% +/- 76%, and 357% +/- 26% of baseline, respectively; P < .001). VIP
      infusion at 12 ng/min and 480 ng/min completely inhibited the increased intensity
      of contraction at neostigmine doses of 0.10 and 0.15 mg, respectively. Our
      results show that VIP decreases the intensity and the duration of pyloric
      contraction in a dose-dependent manner. As pyloric spasm may contribute to the
      pathogenesis of hypertrophic pyloric stenosis, we can postulate a role for
      reduced VIP-induced relaxation in the pathophysiology of hypertrophic pyloric
      stenosis.

PMID- 8308674
TI  - Glucose utilization in the surgical newborn infant receiving total parenteral
      nutrition.
AB  - Glucose is the main source of nonprotein calories in total parenteral nutrition
      (TPN). However, its use has been associated with various nutritional, metabolic,
      and respiratory complications. The aim of this study was to determine, in the
      stable surgical newborn infant, the characteristics of carbohydrate metabolism,
      in particular the maximum oxidative threshold for intravenous glucose and the
      thermogenic effect of glucose. Twenty-one studies were done on 11 infants (weight
      2.82 +/- 0.19 kg) receiving TPN containing constant amounts of amino acids (2.5
      g/kg/d) and fat (3.0 g/kg/d), and different amounts of glucose (range, 10 to 25
      g/kg/d). Oxygen consumption (VO2), carbon-dioxide production (VCO2), and resting
      energy expenditure (REE) were measured by indirect calorimetry. Urinary nitrogen
      excretion rate was measured and substrate utilization calculated from the
      nonprotein respiratory quotient (NPRQ). There was a positive correlation between
      the predictor variable glucose intake and the dependent variables VO2 (r = .55; P
      < .05), VCO2 (r = .83; P < .0001), REE (r = .65; P < .005), NPRQ (r = .94; P <
      .0001), respiratory rate (r = .46; P = .06), and plasma triglycerides level (r =
      .67; P < .01). When glucose intake exceeded 18 g/kg/d the NPRQ was greater than
      1.0, indicating glucose conversion to fat. Above this level of intake, the
      gradient of the correlation between the predictor variable glucose intake and the
      dependent variables VCO2 and REE increased. From this study we conclude that: (1)
      Glucose intake is the principal determinant of glucose utilization and exerts an
      influence on the metabolism of exogenous fat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308675
TI  - Cat-scratch disease: an unusual presentation.
AB  - A 2-year-old child was found to have mesenteric lymphoadenopathy during
      investigation of a fever of unknown origin. The lymphadenopathy persisted at
      follow-up 2 months later. Workup for an infectious etiology was negative. A
      laparotomy and excisional biopsy was performed to eliminate lymphoma. Pathology
      showed enlarged lymph nodes containing granulomas with giant cells and central
      caseating necrosis. Warthin-Starry staining showed cat-scratch bacilli within the
      necrotic material. Cat-scratch disease is a well-recognized cause of regional
      adenopathy in children and usually resolves without treatment. Intraabdominal
      involvement, consisting of hepatic and splenic lesions, often associated with
      retroperitoneal adenopathy, has been reported. Isolated mesenteric adenopathy is
      an unusual presentation of this disease but should be included in the
      differential diagnosis of intraabdominal lymphadenopathy.

PMID- 8308676
TI  - Thoracoscopy in the management of empyema in children.
AB  - Many pediatric surgeons advocate early open drainage or decortication for
      children with acute empyema. Unfortunately, such procedures can be associated
      with significant morbidity. Since 1981, we have used early thoracoscopic
      adhesiolysis and pleural debridement as an alternative to open thoracotomy in 9
      children with acute empyema. The average age was 7.8 +/- 1.8 years (range, 2 to
      16). All patients had failed initial treatment, which included antibiotics and
      chest tube drainage. All procedures were performed under general anesthesia.
      Following thoracoscopy, 8 of the 9 patients were managed with a single drainage
      tube and the average duration of tube drainage was 8.4 +/- 1.4 days. One patient
      died of underlying leukemia. Of the 8 patients who recovered, the average
      postoperative hospital stay was 13.4 +/- 2.9 days. No complications resulted from
      the thoracoscopies and there was no need for further surgical intervention in any
      of these patients. We conclude that thoracoscopy allows for minimally invasive,
      yet effective treatment of acute empyema with loculated collections.
      Thoracoscopic visualization of the pleural cavity permits efficient debridement,
      thorough adhesiolysis, and optimal placement of drainage tubes. Since we have
      begun using early thoracoscopy in the treatment of pediatric empyema, open
      drainage or decortication has not been required in any of these patients.
      Thoracoscopy is a useful adjunct in the treatment of empyema in children and its
      early application may eliminate the need for decortication.

PMID- 8308677
TI  - Childhood primary pulmonary neoplasms.
AB  - Nine children (6 boys, 3 girls) were diagnosed with a primary endobronchial or
      pulmonary parenchymal neoplasm. The average age at diagnosis was 9 years.
      Presenting complaints included cough (7), fever (5), pulmonary infection (3),
      respiratory distress (3), weight loss (2), pain (2), and hemoptysis (1).
      Pulmonary x-rays showed persistent atelectasis, pneumonic infiltrates or mass
      lesions. A computed tomography scan was performed in 8. Five of six endobronchial
      tumors were diagnosed with bronchoscopy and biopsy. Treatment consisted of
      thoracotomy and pulmonary resection in 7 cases and laser resection in 2. The
      pathologic diagnoses were bronchial carcinoid (3), bronchial mucoepidermoid
      carcinoma (1), inflammatory pseudotumor (plasma cell granuloma) of the bronchus
      (2) and of the lung parenchyma (1), fibrosarcoma (1), and rhabdomyosarcoma (1).
      Postoperative chemotherapy was given only to the patient with pulmonary
      rhabdomyosarcoma; this child died. One child has developed a local recurrence
      while 7 children are alive and free of disease at an average of 2.4 years
      postresection. Pulmonary neoplasms are unusual in the pediatric age group and
      represent a wide spectrum of pathology. Including the present series, 383 tumors
      have been described. Seventy-six percent were malignant. Early investigation and
      surgical intervention are essential in children with persistent pulmonary
      symptoms or x-ray abnormalities. In most cases, the prognosis is excellent with
      complete surgical resection; however, malignancies other than bronchial adenoma
      are associated with significantly mortality.

PMID- 8308678
TI  - Optimal management of patent ductus arteriosus in the neonate weighing less than
      800 g.
AB  - Between January 1988 and December 1990, 132 neonates weighing < 800 g were
      admitted to our neonatal intensive care unit. Of the 76 who survived initial
      resuscitation, 42 had developed a hemodynamically significant patent ductus
      arteriosus (PDA) (mean +/- SD): gestational age 25.3 +/- 1.9 weeks, birth weight
      650 +/- 93 g. Two infants were referred for primary surgical ligation because of
      contraindications to indomethacin. Forty infants were initially treated with
      indomethacin. Seventeen of 40 (43%) were subsequently referred for surgical
      ligation because of indomethacin failure. Infants requiring surgical duct closure
      were a lower gestational age (24.6 +/- 1.3 v 25.7 +/- 2.0 weeks, P = 0.49) and
      had a greater left atrial-aortic (LA/Ao) ratio on echocardiography (1.71 +/- 0.28
      v 1.46 +/- 0.26, P = .04) compared with those treated successfully with
      indomethacin. There were 6 deaths (15%), all of which occurred in infants
      receiving indomethacin (5 indomethacin alone, 1 indomethacin+ligation).
      Indomethacin was directly associated with intestinal perforation in 3 patients,
      and acute renal failure in 1; all 4 died. Surgery was associated with minimal
      morbidity (intraoperative transfusion in 1, postoperative pneumothorax requiring
      chest tube in 1). These data suggest that in the extremely premature neonate with
      a hemodynamically significant PDA: (1) indomethacin therapy is associated with a
      high failure rate and significant complications; (2) PDA associated with a large
      LA/Ao ratio is unlikely to close with indomethacin therapy; and (3) surgical duct
      closure is associated with minimal morbidity. We conclude that primary surgical
      ligation may provide the optimal management for PDA in carefully selected
      patients.

PMID- 8308679
TI  - Giant hydatid lung cysts in the Canadian northwest: outcome of conservative
      treatment in three children.
AB  - Hydatid lung disease due to Echinococcus granulosus in the Canadian northwest and
      Alaska is often asymptomatic and usually benign. We reviewed the course and
      outcome of three children with giant hydatid lung cyst seen over a 2-year period.
      All were North American Indian children aged 9 to 12 years who presented with
      cough, fever, and chest pain. One had a rash. There was a history of exposure to
      domestic dogs who had been fed moose entrails in each case. Chest x-rays showed
      solitary lung cysts with air-fluid levels, from 6 cm to 12 cm in diameter.
      Aspiration of each cyst demonstrated Echinococcus hooklets and protoscolices.
      Serology was unhelpful, being negative in two cases. Transient pneumonitis and
      pneumothorax were seen as complications of needle aspiration. Two cysts gradually
      resolved over the following 6 months. One child returned after 9 months with a
      lung abscess due to superimposed infection of the cyst remnant with Haemophilus
      influenzae, and eventually required lobectomy. The existence of an endemic benign
      variant of E granulosus in Canada is not widely known, and it is important to
      distinguish it from the more aggressive pastoral form of the disease seen in
      immigrants from sheep-rearing countries. The native Canadian disease usually
      resolves spontaneously, does not cause anaphylaxis, and does not implant daughter
      cysts if spilled. Surgical treatment should be avoided except for complications
      such as secondary bacterial infection.

PMID- 8308680
TI  - Pentoxifylline improves resting membrane potential in sepsis.
AB  - The resting membrane potential (RMP) of skeletal muscle cells was investigated in
      a hyperdynamic animal model of sepsis. Reduced membrane potential is known to
      parallel the clinical course of sepsis and hemorrhagic shock in animal models.
      Pentoxifylline (PTF), a dimethyl xanthine derivative of the theophylline family,
      may improve the metabolic effects of sepsis. A cecal ligation and puncture (CL&P)
      sepsis model in Wistar rats was used in which RMP was measured with differing
      administration regimes of PTF. The RMP decreased less rapidly in our study when
      PTF was administered after CL&P and this effect was most noticeable after 18
      hours. Administration of PTF before CL&P had little effect on membrane potential
      fall-off. These results suggest a potential role for PTF in the management of
      sepsis.

PMID- 8308681
TI  - Pure esophageal atresia: outlook in the 1990s.
AB  - Eleven newborns with pure esophageal atresia were treated between 1980 and 1989
      inclusive; there were six girls and five boys. Their gestational age ranged from
      31 to 40 weeks (average, 37 weeks) and weight from 1.1 to 3.0 kg (average, 2.2).
      The only associated anomalies were Down's syndrome, respiratory distress
      syndrome, and patent ductus arteriosus. All babies received an immediate
      gastrostomy. Several radiologic studies were done to see if the distance between
      the two esophageal pouches was decreasing. Dilatations of the upper pouch were
      carried out in two patients. After a wait of 1 to 7 months (average, 3 1/2) a
      primary anastomosis was attempted; the weight of six babies doubled during this
      time. Eight neonates had a primary repair (two were aided by a circular myotomy).
      Two had a staged gastric tube constructed, and one baby had a gastric pull-up
      procedure. Three of the infants with a primary anastomosis required a subsequent
      antireflux operation, and one needed her anastomosis resected 16 months later.
      Ten of these 11 newborns are alive and well; one of the gastric tube children
      died from an adhesive small bowel obstruction at age four years.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8308682
TI  - Fetal tumors associated with hydrops: the role of the pediatric surgeon.
AB  - Fetal tumors are being diagnosed with increasing frequency and great accuracy by
      antenatal ultrasound. High-output cardiac failure and hydrops indicate fetal
      distress. Management may be limited by the gestational age of the fetus. Our
      experience with three fetal tumors demonstrates the dilemma with respect to
      timing of delivery and prognosis. Following the diagnosis of a large
      sacrococcygeal tumor, a 22-week-gestation fetus became hydropic and died. Another
      fetus with a rapidly growing posterolateral chest wall mass required cesarean
      section delivery at 29 weeks gestation. Postnatal course was complicated by
      pulmonary hypoplasia, intratumoral hemorrhage, and death. The third fetus had an
      enlarging tumor in the right lobe of the liver. Poor biophysical profile and mild
      hydrops necessitated cesarean section delivery at 34 weeks. Right hepatic
      lobectomy was performed and the infant was subsequently discharged home at one
      month of age. The deleterious effects of the fetal tumor and the need for its
      removal have to be carefully weighed against the ability of the fetus to survive
      postnatally.

PMID- 8308683
TI  - Indications for laparotomy after hydrostatic reduction for intussusception.
AB  - A criterion for successful hydrostatic reduction of intussusception is reflux
      into the terminal ileum. In our practice, absence of reflux into the terminal
      ileum is not an indication for laparotomy if the radiographic appearances suggest
      edema of the ileocecal valve. The aim of this study was to validate our approach.
      We reviewed the case notes of patients with a diagnosis of intussusception (n =
      107; age 11.74 +/- 1.48 months; mean +/- SEM) treated from 1987 to 1991. Eleven
      required primary laparotomy for peritonitis. Ninety-six patients who had a
      contrast enema were studied. Edema of the ileocecal valve was defined as a
      persistent filling defect in the cecum after apparently complete hydrostatic
      reduction, without reflux of contrast into the distal small bowel. In 59 patients
      hydrostatic reduction was successful: 11 (18.6%) had edema of the ileocecal valve
      and no reflux contrast into the terminal ileum (group B). All improved clinically
      after the enema and needed no further treatment. In 37 patients hydrostatic
      reduction of the intussusception was unsuccessful and an operation was performed:
      26 (70.3%) required manual reduction of the intussusception (group C) and 11
      (29.7%) underwent bowel resection (group D). None of the patients with edema of
      ileocecal valve required further treatment or developed recurrent
      intussusception. In none of the patients who had an operation was the
      intussusception found to have been reduced by the contrast enema. There were no
      deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308684
TI  - Anorectal function in adults operated for a benign sacrococcygeal teratoma.
AB  - Fecal continence and quality of life were evaluated by a questionnaire in 26
      adult patients (mean age, 30 years; 6 men, 20 women) who had undergone surgery
      for a benign sacrococcygeal teratoma in infancy. The fecal continence was
      assessed by a score described by Holschneider. Twenty-six healthy people with a
      similar age and sex distribution were used as controls. Good fecal continence was
      reported by 88% of the patients; however, only 27% had completely normal bowel
      habits. Some fecal soiling was present in 27% of the patients. No correlation
      between the severity of aberrations in anorectal functions and the degree of
      intrapelvic extension of the tumor was found. Social problems related to
      deficient anorectal function were reported by 27% of the patients. Other health
      problems including urinary incontinence were reported by 50% of the patients. All
      the controls had good fecal continence; 77% of them had completely normal bowel
      habits. The present study shows that at the adult age, a significant proportion
      of patients who have undergone surgery for sacrococcygeal teratoma suffer from
      deficient anorectal function and a diminished quality of life.

PMID- 8308685
TI  - Fetal neuroblastoma: prenatal diagnosis and natural history.
AB  - Obstetrical sonography has helped diagnose and define the features of some
      congenital malformations and tumors. We present five fetal neuroblastomas
      detected by routine prenatal sonography. All were adrenal tumors diagnosed
      between 26 and 39 weeks gestation. All 5 tumors were completely resected
      postnatally and the patients have remained disease free from 2 months to 10 years
      after resection without adjuvant therapy. A literature review collated 16 other
      cases of fetal neuroblastoma detected by sonography between 29 and 38 weeks
      gestation. These cases included 1 cervical, 1 thoracic, and 14 adrenal tumors.
      Thirteen neonates had Evans stage I or II tumors, and three had more advanced
      disease. Eleven mothers did not have hypertension or preeclampsia during the
      pregnancy, and the neonates all had stage I or II disease. Four mothers had
      hypertension or preeclampsia. Three of these neonates had stage IV or IVS disease
      with liver metastases, and all three had fetal hydrops. Review of the congenital
      neuroblastoma literature documented 71 cases diagnosed soon after birth, and
      several of these cases had unusual features that could have been detected by
      prenatal ultrasound. Four of the tumors were so large that dystocia resulted and
      fetal dismemberment was required for delivery. Eight of the tumors metastasized
      to the placenta, and 1 metastasized to the umbilical cord with subsequent fetal
      death. We conclude that fetal neuroblastoma can be diagnosed by prenatal
      sonography. Accurate staging is difficult by sonography, but in mothers with no
      preeclampsia symptoms the chance of widely disseminated disease is
      small.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308686
TI  - Allopurinol protects the bowel from necrosis caused by indomethacin and temporary
      intestinal ischemia in mice.
AB  - The present study was undertaken to evaluate if allopurinol administration
      protects mice from bowel necrosis caused by temporary intestinal ischemia
      followed by indomethacin (INDO). We have previously reported that ischemia (15
      minute occlusion of superior mesenteric vessels) followed by intravenous (i.v.)
      INDO caused significant bowel necrosis in CD-1 mice. Ischemia or INDO alone did
      not cause necrosis. To investigate protective measures against necrosis, we used
      CD-1 mice, 25 to 30 g. Forty-four animals were gavage fed 1 mL of water for 7
      days and 32 animals were gavage fed 10 mg/kg allopurinol for 7 days. On the
      seventh day all animals were anesthetized and the superior mesenteric vessels
      occluded for 15 to 20 minutes, followed by i.v. INDO (0.5 mg/kg) once daily for 3
      days. Animals who died were examined for bowel necrosis and all animals were
      killed 7 days after surgery and necropsied. Of the 44 saline-fed animals, 12
      developed bowel necrosis (27%). Of the 32 allopurinol-fed animals, 1 developed
      necrosis (3%). The result of Fisher's exact two-tailed test was P = .006.
      Pretreatment with oral allopurinol significantly protects the mice from
      developing bowel necrosis when the mesenteric vessels are temporarily occluded
      and INDO is administered. Allopurinol may prevent reperfusion injury by
      inhibiting formation of xanthine oxidase generated, oxygen-derived free radicals
      and may be valuable in pretreating premature infants with patent ductus
      arteriosus who have had an ischemic episode in whom INDO use is contemplated.

PMID- 8308687
TI  - Chronic esophagitis and gastric metaplasia are frequent late complications of
      esophageal atresia.
AB  - Long-term follow-up examination with esophagogastroduodenoscopy was performed on
      39 esophageal atresia patients 2 to 11 years (mean, 7.6) after the anastomotic
      operation. Nine of these patients had undergone fundoplication for symptomatic
      gastroesophageal reflux. The subjective results at the last follow-up were as
      follows: excellent in 25, good in 10, and fair in 4 patients. The endoscopic
      findings were normal in 17 patients. Endoscopy of the remaining 22 patients
      showed esophagitis in 20, 5 associated with Barrett's change. Hiatal hernia was
      found in 10 patients. The fundoplication was totally or partially disrupted in 3
      patients. Esophageal biopsies were obtained from 37 patients. The histological
      findings were as follows: esophagitis in 21, gastric metaplasia in 3, and normal
      esophageal mucosa in 13 patients. The endoscopic and histological findings
      correlated poorly with subjective results as more than half of the patients with
      excellent subjective results had esophagitis, one of them with gastric
      metaplasia. Therefore, long-term endoscopic follow-up of all esophageal atresia
      patients is warranted.

PMID- 8308688
TI  - Treatment of giant omphalocele by enlargement of the abdominal cavity with a
      tissue expander.
AB  - Even in the absence of major associated anomalies, treatment of giant
      omphaloceles is difficult primarily because of the disproportion between the
      large volume of the omphalocele and the small volume of the intraabdominal
      cavity. The case of a child is presented in whom conservative treatment had to be
      abandoned. Reduction of the omphalocele contents and closure of the defect was
      successfully accomplished after a 19-day period of enlargement of the abdominal
      cavity by means of an intra-abdominally placed tissue expander.

PMID- 8308689
TI  - Routine inguinal hernia repair in the pediatric population: is office follow-up
      necessary?
AB  - Routine inguinal hernia repair in the pediatric population has a low complication
      rate. Very few complications are identified at follow-up, which brings into
      question the necessity of the traditional postoperative visit. A retrospective
      review of patients who had undergone a routine inguinal hernia repair in 1991 at
      our institution was done in order to determine our current follow-up practices
      and complication rate. To determine the perceived necessity for the follow-up
      visit, parents were given a short telephone questionnaire. Of 175 eligible
      patients, questionnaires were completed on 145. Of these 145 patients, 77 were
      seen in follow-up by the pediatric surgeon only, 43 by the family doctor only, 12
      were seen by both, and 13 patients had no physician follow-up. The sole
      complication was a stitch abscess (complication rate 0.7%). Results of the
      questionnaire showed that 90% of parents felt the follow-up visit was "helpful,"
      80% felt it was "necessary," and 35% would have been satisfied with telephone
      follow-up. The main purpose of the postoperative visit appears to be parental
      reassurance. Careful preoperative and postoperative instruction and reassurance
      may be sufficient in a significant number of cases.

PMID- 8308690
TI  - Malignant risk in juvenile polyposis coli: increasing documentation in the
      pediatric age group.
AB  - The presence of juvenile polyps with resulting bleeding and abdominal pain has
      traditionally been considered a benign, self-limiting process which would resolve
      with age. The dictum that these polyps were usually solitary, were found
      predominantly in the rectosigmoid area, and were without malignant potential has
      been reconsidered in recent years with the increased use of colonoscopy. Several
      case reports in both adults and children have documented the presence of
      adenomatous changes in this syndrome. We report 3 cases of children, ages 3, 11,
      and 11 who were found to have adenomatous polyps in the midst of fields of
      juvenile polyps on evaluation for rectal bleeding. All three were treated
      definitively with endorectal pull-through. Two of these patients had atypia on
      histological evaluation, one of which was severe. We recommend a more aggressive
      approach to patients found to have multiple juvenile polyps on barium enema,
      including colonoscopic biopsies at several sites to determine the presence of
      adenomatous changes, with colectomy and endorectal pull-through should these be
      found.

PMID- 8308691
TI  - Anal fistula in infants: etiology, features, management.
AB  - Anal fistulas in infants are poorly understood. A high incidence of recurrence
      has been attributed to a congenital abnormality of the anal crypts. To verify
      this hypothesis, we reviewed all anal fistulas seen in children less than 2 years
      of age and treated between 1980 and 1991. All patients were males with a mean age
      of 9.5 months, and only 3 had other illnesses. Ninety-two percent have had
      previous anorectal abscesses. The fistulas were single in 31 patients and double
      in 5. Their origin in the crypts was clearly identified in 14 cases. When
      anoscopy was routinely performed, deep thick-walled crypts were found in 47% of
      the cases. In most instances only one crypt was abnormal. The operative
      management included fistulotomy in 17 patients and fistulectomy in 9.
      Cryptotomies besides fistula excision were performed in 9 cases, and concurrent
      abscess drainage in 6. Follow-up was available in 31 patients for a mean length
      of 20 months. There were 4 complications (11%): one abscess requiring drainage,
      one wound infection treated conservatively, one granuloma, and one postoperative
      laryngitis. No recurrences were observed and none of the patients had fistula
      related complaints at the last visit. Anal fistulas in infants are observed
      exclusively in males and are often related to abnormal crypts. Although 92% of
      fistulas are preceded by a perianal abscess, only 42% of perianal abscesses will
      result in fistula formation. Anal fistulas can be treated by either fistulotomy
      or fistulectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308692
TI  - Posterior sagittal rectal myectomy for persistent rectal achalasia after the
      Soave procedure for Hirschsprung's disease.
AB  - For the management of persistent rectal achalasia after the Soave endorectal pull
      through procedure, we have used posterior sagittal myectomy of the remaining
      aganglionic rectal muscular cuff, and have had satisfactory outcomes in five
      patients. Via a posterior sagittal skin incision, the posterior aspect of the
      rectal muscular cuff is reached. With the striated muscular complex retracted
      downward, the level of the dentate line is identified on the posterior wall of
      the rectum with the aid of the surgeon's finger inserted inside the anorectum.
      Two parallel longitudinal incisions are made on the rectal muscular cuff to
      create a muscular strip which is elevated and excised; the distal end of the
      myectomy strip is at the level of the dentate line and includes a part of the
      internal and sphincter muscle. During the last 4 years, we performed this
      procedure in 5 patients with remarkable relief of constipation, distension, and
      enterocolitis. The advantages of this procedure include: (1) less technical
      difficulty than the transanal approach, (2) avoiding colostomy, and (3) promising
      results.

PMID- 8308693
TI  - Fetal lambs with surgically produced congenital diaphragmatic hernia (CDH) are
      deficient in pulmonary surfactant.

PMID- 8308694
TI  - Mathematical model for the selective deposition of inhaled pharmaceuticals.
AB  - To accurately assess the potential therapeutic effects of airborne drugs, the
      deposition sites of inhaled particles must be known. Herein, an original theory
      is presented for physiologically based pharmacokinetic modeling and related
      prophylaxis of airway diseases. The mathematical model describes the behavior and
      fate of particles in the lungs of adult human subjects under various breathing
      conditions. Their deposition patterns are calculated via superposition of the
      separate but not independent processes of inertial impaction, sedimentation, and
      diffusion. The related computer code is designed to calculate total and
      compartmental (tracheobronchial and pulmonary) distributions of inhaled aerosols.
      In this manuscript, the model is first tested via comparisons of predicted
      deposition patterns with laboratory data from human inhalation exposure
      experiments and then it is applied to determine which factors most influence the
      dosimetry of inhaled particles. In this format, deposition patterns are
      explicitly related to particle characteristics, ventilatory parameters, and
      intersubject variabilities of lung morphologies. The dosimetric model was
      developed to improve the efficacy of aerosol therapy via the selective deposition
      of inhaled pharmaceuticals at prescribed lung locations to elicit optimum
      effects.

PMID- 8308695
TI  - Synthesis and antineoplastic evaluation of alpha-substituted alkanesulfonates:
      analogues of clomesone.
AB  - 2-Chloroethyl (methylsulfonyl)methanesulfonate (clomesone) is highly effective
      against certain experimental neoplasma and is now undergoing initial clinical
      trials. Two groups of analogues have been prepared to explore further the
      anticancer activity of this type of sulfonates. The first group is comprised of
      several 2-chloroethyl sulfonates that have electron-attracting groups alpha to
      the sulfonate group; among these, the alpha-chloroethanesulfonate and the
      (trifluoromethyl)-methanesulfonate caused increases in lifespan of 45 and 72%,
      respectively, in tests against P388 leukemia in mice. The second group is
      comprised of several (methylsulfonyl)methanesulfonates that possess alkylating
      groups other than the 2-haloethyl groups. 2-Hydroxyethyl
      (methylsulfonyl)methanesulfonate was active against P388 leukemia (increases in
      lifespan, 66 and 94%), but was less effective than clomesone, which effects
      cures. The 3-chloropropyl and the propyl derivatives caused modest increases in
      lifespan. Therefore, several 2-chloroethyl alpha-substituted methanesulfonates
      are less effective against P388 leukemia than is the alpha-(methylsulfonyl)
      derivative (clomesone), and several substituted alkyl
      (methylsulfonyl)methanesulfonates are also less effective than is the 2
      chloroethyl derivative (clomesone). The synthesis of clomesone was simplified to
      one operational step from methanesulfonyl chloride.

PMID- 8308696
TI  - Dual sorption model for the nonlinear percutaneous permeation kinetics of
      timolol.
AB  - The nonlinear percutaneous permeation kinetics of timolol were studied in vitro
      with human cadaver skin. In the sorption isotherm (equilibrium) study, the plots
      of the amount of timolol per unit area of epidermis versus aqueous timolol
      concentration in equilibrium were curvilinear as the dual sorption model
      predicts. In the penetration study, several aqueous timolol concentrations were
      maintained in the donor cell for 25 h. The lag-time was prolonged as the timolol
      concentration in the donor cell was decreased. The change in the lag time was
      analyzed by a newly proposed method with the lag-time prolongation factor that is
      calculated from the parameter values obtained in the sorption isotherm study. The
      ratio of the lag-time to lag-time prolongation factor was of the same magnitude,
      indicating that the dual sorption model explains the nonlinear percutaneous
      permeation kinetics of timolol. Finally, the diffusion parameter for the mobile
      solute was estimated by fitting the data of the cumulative amount excreted into
      receptor cell versus time to the numerical solution of the dual sorption model.
      The observed data were roughly compatible with the values predicted by the dual
      sorption model.

PMID- 8308697
TI  - Effects of insulin and acarbose alone and in combination in the female
      streptozotocin-induced diabetic rat.
AB  - Diabetes is characterized by hyperphagia, polydipsia, polyuria, elevations in
      blood and urinary glucose, and alterations in the adrenergic nervous system.
      Insulin treatment is effective in reversing most of the adverse conditions of
      diabetes in the streptozotocin-treated rat. Acarbose (BAY G 5421), an intestinal
      alpha-glucosidase inhibitor, decreases postprandial glycemia by delaying
      carbohydrate absorption and also affords some beneficial effects in the diabetic
      animal. The purpose of this study was to evaluate the effects of chronic insulin
      (< or = 2 U/day) with and without acarbose treatment (20 mg/100 g of diet) on the
      metabolic and adrenergic parameters altered in streptozotocin (50 mg/kg,
      intravenously)-induced diabetes in female rats. Insulin dosage was changed weekly
      after the first 2 weeks of treatment in both insulin-treated groups in an attempt
      to maintain a level of blood glucose that was comparable to that achieved with
      acarbose treatment alone. Insulin dosage was reduced to a greater extent in the
      dual-treated group than in the group treated with insulin alone. Diabetic rats
      were hyperphagic, polydipsic, and polyuric within 1 week of streptozotocin
      treatment. Each treatment alone was effective in reducing these alterations.
      However, these reductions were more apparent in the combined therapy group. Only
      in this combined therapy group was glycated hemoglobin returned to normal. All
      treatments also prevented the significant weight loss observed in untreated
      diabetic animals. Adrenergic responses were assessed by monitoring the rise in
      tail skin temperature associated with administration of isoproterenol. Diabetic
      rats were less responsive than controls, and each of the treatments restored this
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308698
TI  - Properties and cost effective method for production of the antitumor agent
      declauxin from sporulating Penicillium herquei.
AB  - Duclauxin, an antitumor agent, was isolated from sporulating Penicillium herquei
      (ATCC34665) grown on a medium of peanut hulls supplemented with potato starch
      solution (termed "Gostar"). The medium was inoculated with a sporulating
      subculture of P. herquei established on a 2% potato starch slurry supplemented
      with mineral salts. The P. herquei grew as well on Gostar as on an enriched
      medium. Duclauxin was isolated in crystalline form from Gostar-grown P. herquei.
      Comparison of costs of duclauxin obtained from inexpensive Gostar versus costly
      enriched media indicated that Gostar reduces production expenses. Duclauxin was
      not effective as an antibiotic against certain species of gram-positive and gram
      negative bacteria, fungi, and viruses, but a concentration-dependent inhibition
      of wheat coleoptile growth was observed. Duclauxin was characterized by melting
      point, optical rotation, IR and NMR spectroscopy, MS and X-ray diffraction.

PMID- 8308699
TI  - In vitro evaluation of the antimicrobial activities of selected lozenges.
AB  - The in vitro antimicrobial activities of 10 lozenges (Merothol, Merocets,
      Merocaine, Strepsils (two varieties), Dequacaine, Dequacets, Zensyls, Tyrozets,
      and Labosept) were determined by use of a microtiter counting method with
      Streptococcus pyogenes, Staphylococcus aureus, and Candida albicans as the test
      organisms. Merothol, Merocets, Merocaine, and both Strepsils formulations all
      reduced the counts of both S. aureus and S. pyogenes suspensions by approximately
      6 log cycles within 5 and 20 min, respectively. Merothol, Merocets, and Merocaine
      also caused a reduction in the counts of the C. albicans suspension approximately
      5 log cycles within 40 min, but no other lozenge formulation showed rapid and
      marked activity against C. albicans. Dequacaine and Dequacets showed marked but
      much slower activities against this yeast. Zensyls caused an approximately 6-log
      cycle reduction in bacterial counts within 40 min, and Dequacaine, Dequacets, and
      Tyrozets showed marked but slower antibacterial activities. This work confirmed
      by a statistically sound in vitro method the in vivo antibacterial activities
      reported for Merothol, Merocets, and Merocaine, demonstrated equivalent
      antibacterial activities for Strepsils, and indicated that Merothol, Merocets,
      and Merocaine also showed marked activities against C. albicans.

PMID- 8308700
TI  - Elucidation of the role of hydrophobic bonding in influencing intestinal
      absorption of model sulfonamides and revealing possible mechanism of drug
      absorption in rat model.
AB  - A recirculation technique was used to study the first-order kinetics of
      intestinal absorption of un-ionized sulfadiazine, sulfamerazine, and
      sulfamethazine in rats in situ at 32, 35, and 38 degrees C. The absorption rate
      constant (Kab) of each sulfonamide increased with increase in temperature and, at
      each temperature, Kab was the highest for sulfamethazine and the lowest for
      sulfadiazine. Applying the activated complex formation theory, the energy of
      activation (Ea), free energy of activation (delta F*), enthalpy of activation
      (delta H*), and entropy of activation (delta S*) of absorption were determined
      for the sulfonamides to gain some insight into the mechanism of their intestinal
      absorption. The high values of delta F* indicated that the barrier for
      sulfonamide absorption was great. For each drug, the value of delta H* was
      positive and that the delta S* negative. However, delta H* and delta S* were the
      highest for sulfamethazine and the lowest for sulfadiazine, thus revealing the
      influence of hydrophobic bonding in increasing Kab of the sulfonamides with the
      increase in methyl group content of their molecules. By considering the facts
      that (1) the microvillus membrane of the intestinal absorptive cells regulates
      the rate of passive absorption of drugs, (2) the microvillus membrane is rich in
      proteins, which are located external to the membrane and exposed to the
      intestinal fluid, and (3) hydrophobic bonding contributes to the activation
      parameters of absorption, it was postulated that the activated complex formed in
      the absorption process consisted of a transient association of the sulfonamide
      molecules with some protein component of the microvillus membrane.

PMID- 8308701
TI  - Determination of serum biotinidase activity with biotinyl derivatives of
      lodotyramines as substrates.
AB  - We synthesized biotinylated mono- and di-iodotyramine and their radioactive
      counterparts and used these substances as substrates to estimate serum
      biotinidase activity in a radioassay system. The Km values determined for mono-
      and di-iodobiotinyl derivatives were 15.8 and 25.9 microM, respectively, whereas,
      the maximum velocities of the enzymatic reaction were 27.0 and 8.7 nmol.min-1.mL
      1, respectively. Both substrates competed with biocytin for the same active site
      of the enzyme and the Ki values were 7.30 and 9.56 microM for the mono- and di
      iodinated substrate, respectively. Higher assay sensitivity was obtained using
      [125I]biotinyl-monoiodotyramine as substrate, and the values obtained were
      directly related with those determined with the well-established colorimetric
      method (r = 0.9377, n = 31). However, for routine use, the assay may be
      accomplished by diluting the radiotracer with biocytin instead of its "cold"
      counterpart, because it is a commercially available reagent. The values obtained
      in this case were very well correlated with those determined by the colorimetric
      assay as well (r = 0.9289, n = 31).

PMID- 8308702
TI  - Prodrugs of 2',3'-didehydro-3'-deoxythymidine.
AB  - Six ester prodrugs of 2',3'-didehydro-3'-deoxythymidine (D4T) were synthesized,
      and their physicochemical properties were evaluated. Marked differences were
      observed. All of the prodrugs were chemically stable within the pH range 2-7.
      Hydrolysis of these esters was observed in all cases for four rat enzyme systems
      (plasma, liver, duodenum, and kidney), with D4T being regenerated. D4T or the
      prodrug was administered orally to rats, and the plasma concentrations of D4T and
      a corresponding prodrug were measured. The half-life of D4T after intravenous
      administration was 35.9 min. The half-life calculated from the terminal phase and
      the maximum concentration in plasma following oral administration of D4T were
      35.9 min and 48.4 microM, respectively. After oral prodrug administration (with
      water or olive oil as a solvent), though none of the prodrugs was detected in
      plasma except for 5'-hemisuccinyl D4T and 5'-hemiglutaryl D4T with olive oil as a
      solvent, retention time of plasma D4T concentration was extended and the elevated
      D4T concentration in plasma decreased.

PMID- 8308703
TI  - Investigation of the particle size distribution of a model intravenous emulsion.
AB  - The size distribution of a model intravenous (iv) emulsion was investigated with
      special regard to the lower size classes. The special interest in the lower size
      classes is related to their possible responsibility for a number of side effects
      as well as their possible influence on pharmacokinetics of incorporated drugs.
      The particle size distribution of the unfractionated emulsion observed by photon
      correlation spectroscopy (PCS) showed no particles with diameters < 140 nm. In
      contrast, a three-dimensional analysis of transmission electron micrographs (TEM)
      resulted in a mean particle diameter of approximately 68 nm. 31P NMR experiments
      revealed that approximately 48 mol% of the emulsifier forms particles smaller
      than approximately 100 nm in diameter. The results from TEM observations and NMR
      spectroscopy suggest that the majority of particles by number have diameters <
      100 nm. PCS measurements of fractionated samples of the emulsion, in combination
      with their chemical analysis, confirmed the predominance of particles with
      diameters < 100 nm. The relevance of PCS data analysis for the characterization
      of unfractionated iv emulsions, consisting of particles differing in structure
      and showing a broad size distribution by number, seems limited.

PMID- 8308704
TI  - Ionic size and behavior of diclofenac salts in water and ethanol/water mixtures
      by conductivity at 25 degrees C.
AB  - The objectives of this study were to evaluate the size of the diclofenac ion and
      the electrical behavior of diclofenac salts (DM; M = Li, Na, or K) in
      ethanol/water mixtures. The molar conductance of DM in aqueous solution was
      measured in a dilute concentration range of < 10 mol.m-3 at 25 degrees C. The
      Fuoss-Onsager conductance equation for unassociated electrolytes was used to
      determine the limiting molar conductance (lambda degrees) of DM. The molar
      conductivity of DM at a finite concentration was, however, larger than the value
      calculated by the Fuoss-Onsager limiting law. To correct the difference in the
      experimental data, two equations were employed to fit the experimental molar
      conductance of DM. The size of the diclofenac ion was calculated from the
      limiting molar conductance and compared with the values obtained by the Fedors
      method and the apparent ionization constant (pKa) of sodium diclofenac in
      ethanol/water mixture. The Walden products of DM increased up to 20% (w/w)
      ethanol, but above this concentration of ethanol they decreased. Specific
      interactions between the ions and solvent are discussed.

PMID- 8308705
TI  - Physicochemical characterization of 9,10-anthraquinone 2-carboxylic acid.
AB  - The physicochemical properties of 9,10-anthraquinone-2-carboxylic acid (AQCA)
      were investigated by thermal analysis, powder X-ray diffraction pattern,
      solubility, and partition coefficient. The chemical structure of AQCA was
      confirmed by the data from UV, Fourier transform IR (FTIR), and NMR analyses.
      Solubility and partition coefficient data were pH dependent. A new methanolic
      solvate of AQCA that lost 9.34% of its initial weight from 70 to 100 degrees C
      was found by thermogravimetric analysis. Sublimation of AQCA occurred at
      temperatures > 250 degrees C and needle-like crystals (Form I) were formed. The
      water solubility of AQCA increased with temperature; its heat of solution was
      32.7 kJ/mol. A differential scanning calorimetry-FTIR microscopic system
      correlated a thermal phase transition with structural changes due to loss of
      methanol from the solvate, and three-dimensional FTIR spectra indicated that the
      process was complete by 100 degrees C. The kinetics of desolvation and
      sublimation from each crystal form of AQCA were determined. The activation energy
      of desolvation of methanol from solvate was 425.8 kJ/mol, and the activation
      energy of sublimation from Form I or desolvated crystals was 182.7 kJ/mol.

PMID- 8308706
TI  - Anticonvulsant and neurotoxic activities of twelve analogues of valproic acid.
AB  - Twelve racemic analogues of the antiepileptic drug valproic acid (VPA) were
      tested and compared with VPA for anticonvulsant activity by the subcutaneous
      pentylenetetrazol (PTZ) seizure threshold test and for neurotoxicity by the
      rotorod test. Four compounds produced maximal anticonvulsant activity (100%
      protection) in equimolar doses (1.5 mmol/kg) to VPA and two compounds showed a
      similar effect with lower doses (1.0 mmol/kg). Four compounds produced lower
      activity (38-80% protection), and two compounds showed no anticonvulsant activity
      at the dose used (1.5 mmol/kg). Two of the 12 compounds, (+/-)-2-n-propyl-4
      hexynoic acid (11) and (+/-)-4-methyl-2-n-propyl-4-pentenoic acid (12), showed no
      sedation at doses that produced the maximum anticonvulsant effect. For the first
      time we succeeded to develop two compounds with higher protective index and
      safety ratios than VPA. Compound 11 had a longer duration of action and higher
      protective index but a lower safety ratio than 12. Comparisons of the
      anticonvulsant and minimal neurotoxic effects of these compounds with their
      calculated lipophilicity (C log P) revealed that compounds with the desired high
      anticonvulsant activity and minimal neurotoxicity showed C log P values between
      1.84 and 2.64 and had nine carbon atoms (in contrast to eight carbon atoms for
      VPA).

PMID- 8308707
TI  - Inhibitory effects of procainamide and probenecid on renal excretion of
      sultopride enantiomers in rats.
AB  - The effects of the coadministration of procainamide and probenecid on the
      pharmacokinetic behavior of sultopride, an antipsychotic agent, after intravenous
      administration were studied with rats. The areas under the concentration-time
      curve for and renal clearances of (+)-sultopride and (-)-sultopride, which exist
      as organic cations under physiological pH conditions, were significantly
      decreased (p < 0.01) by the coadministration of procainamide, an organic cation
      under physiological pH conditions. The renal clearance of (-)-sultopride was
      partially decreased (p < 0.05) by the coadministration of probenecid, an organic
      anion under physiological pH conditions. The results suggest that drug-drug
      interactions between organic cations and organic anions occur to a certain extent
      during the tubular secretion process in rats.

PMID- 8308708
TI  - Comparative study of the two polymorphic forms of p-(1R,3S) 3-thioanisoyl-1,2,2
      trimethylcyclopentane carboxylic acid.
AB  - The crystal structure of polymorph I of p-(1R,3S)3-thioanisoyl-1,2,2
      trimethylcyclopentane carboxylic acid has been determined and is compared with
      that of polymorph II that was previously described. Polymorph I is very different
      at the level of the carboxyl group. It does not present disorder and the values
      found for the C-O bonds correspond exactly to single and double bond lengths. In
      addition, the carboxyl groups of the two molecules in the cell packing are
      involved in symmetric hydrogen bonds [2.662(6) A] leading to the formation of a
      dimer around the twofold axis following x with a shift on z. The different
      conformations on the carboxylic group between the two polymorphs are in good
      agreement with the thermodynamic study.

PMID- 8308709
TI  - Permeabilities of alkyl p-aminobenzoates through living skin equivalent and
      cadaver skin.
AB  - The in vitro permeabilities of alkyl p-aminobenzoates through living skin
      equivalent (LSE) and cadaver skin were compared. Methyl, ethyl, and butyl p
      aminobenzoates were used as model compounds. The permeabilities of these
      compounds through LSE and cadaver skin from an aqueous drug suspension were
      determined with a flow-through diffusion cell. The permeability coefficients of
      these esters in LSE were an order of magnitude higher than in cadaver skin. This
      was primarily because of low resistances offered by the outermost layer (i.e.,
      stratum corneum) of LSE. In the case of cadaver skin, the permeability
      coefficient increased as the carbon chain length increased, whereas no
      appreciable change in the permeability coefficients of these esters in LSE was
      observed. These results clearly suggest that the LSE membrane offered very little
      resistance as opposed to cadaver skin. Therefore, the LSE membrane may not
      quantitatively represent a good human skin model for evaluating skin permeation
      of a drug from topical or transdermal formulations.

PMID- 8308710
TI  - Optical crystallographic characteristics of some USP drugs.
AB  - Optical crystallographic data were determined on a variety of newer USP drugs for
      which data had not been previously obtained. The ingredients in an unknown sample
      can be identified by polarized light microscopy by mounting small amounts of the
      material in successive specific refractive index liquids and determining
      refractive indices, optic sign, type of extinction, estimated 2V angle, and other
      optical characteristics for each ingredient present. This information can then be
      compared with the data listed on known drugs and excipients and all of the
      ingredients can be identified. To aid in the identification of unknown drugs,
      optical crystallographic data obtained on 52 of the newer USP drugs are
      presented.

PMID- 8308711
TI  - 1-(Tetrahydro-2-furanyl)-5-fluorouracil (Ftorafur) determined in rat hair as an
      index of drug exposure.
AB  - The fluorescence derivatization of 1-(tetrahydro-2-furanyl)-5-fluorouracil
      (Ftorafur, FT) with 4-bromomethyl-6,7-dimethoxycoumarin (BrMdmc) with 18-crown-6
      as catalyst was utilized for a sensitive and selective liquid chromatographic
      method to determine the concentration of FT in hair. Hair samples collected from
      rats, which had received FT intraperitoneally for 1 to 4 weeks, were dissolved in
      1 M NaOH by heating at 80 degrees C for 30 min. A three-step extraction procedure
      for FT in the dissolved hair was used before and after the derivatization of FT
      with BrMdmc. The detection limit achieved was < 0.16 ng/mg hair. A dose-dependent
      accumulation of FT was evident in the rat hair (r = 0.914, p < 0.001): 0.24 +/-
      0.07, 1.35 +/- 0.39, and 2.85 +/- 0.74 ng/mg hair (mean +/- SD, n = 4-5) at the
      doses of 5, 15, and 50 mg/kg/day for 4 weeks, respectively. In the rats that had
      received the highest dose of FT, the accumulation of FT in the hair depended also
      on the duration of FT administration: 0.82 +/- 0.33 (1 week), 1.52 +/- 0.38 (2
      weeks), and 2.85 +/- 0.74 (4 weeks) ng/mg hair (n = 4-5). These findings suggest
      that the analysis of an oral antineoplasmic FT in the hair may be useful for
      assessing the degree of exposure to the drug.

PMID- 8308712
TI  - Necessary conditions for the pi-electron delocalization in enamino-type muscle
      relaxants.
AB  - Two necessary conditions have been proposed for the pi-electron delocalization
      across four bonds in bis-quaternary bromides of enamino spiro-ketal-type
      compounds. Dynamic NMR data analysis of these compounds suggests that pi-electron
      delocalization takes place if the first atom is nitrogen and the fourth atom is
      either nitrogen or oxygen [i.e., N+ = C-C = N (or O)]. The second condition is
      that the end atoms of the four-bond system should not be the terminal group.

PMID- 8308713
TI  - Evaluation of the bioequivalence of tablet and capsule formulations of
      granisetron in patients undergoing cytotoxic chemotherapy for malignant disease.
AB  - Granisetron is a novel, highly specific 5-hydroxytryptamine receptor antagonist
      given prophylactically to patients undergoing chemotherapy. An open, randomized,
      crossover trial was performed with 37 patients (24 females and 13 males)
      undergoing cytotoxic chemotherapy for malignant disease to compare an oral tablet
      (1-mg tablet given twice daily) with a clinical-trial capsule (1-mg capsule given
      twice daily). Complete pharmacokinetic data were determined for 24 patients (14
      females and 10 males). The concentration of granisetron in plasma was measured by
      HPLC; the limit of quantitation was 0.2 ng/mL. The bioavailability evaluation was
      based mainly on the area under the curve (AUC) (mean values: 52.1 ng.h/mL for the
      capsule and 54.2 ng.h/mL for the tablet) and the maximum concentration (Cmax)
      (mean values: 7.42 ng/mL for the capsule and 8.18 ng/mL for the tablet) measured
      at the steady state after 7 days of continuous therapy. Wide interpatient
      variability in plasma granisetron levels after oral administration was observed.
      The 90% standard confidence interval for the geometric mean ratio overlapped the
      critical range, 0.8-1.25. Point estimates for AUC and Cmax based on two one-sided
      t tests and log-transformed data showed that the upper limit of the confidence
      interval was not within 20% of the mean for the capsule; the corresponding power
      analysis values for AUC and Cmax were 0.89 and 0.81, respectively. Despite
      bioequivalence not being proven, any differences that exist between the two
      formulations are likely to be small. There was no difference in efficacy or
      safety between the two formulations assessed.

PMID- 8308714
TI  - Protection of the rat jejunal mucosa against oxidative injury by cationized
      superoxide dismutase.
AB  - The purpose of the present study was to investigate whether local prevention of
      luminal superoxide-mediated biological damage in the rat jejunal mucosa could be
      achieved by use of cationized superoxide dismutase (SOD). Mucosal damage was
      induced in a closed circulating intestinal loop of the rat either by a mixture of
      xanthine and xanthine oxidase or by a mixture of xanthine, xanthine oxidase, and
      chelated ferrous sulfate. Thus, superoxide radicals or hydroxyl (OH.) radicals
      were induced. The mucosal activity of intracellular lactate dehydrogenase and the
      levels of cellular potassium ions were used to quantitatively characterize the
      tissue damage. SOD was cationized by reaction with N,N'-dimethyl-1,3
      propanediamine to yield a soluble product or with polyhistidine to yield an
      insoluble product. The cationization yield and the activity of the modified
      enzymes were assessed, and the ability of the cationized enzymes to protect the
      rat jejunal mucosa against oxidative stress was studied. It was found that
      cationized SOD provided significant protection against mucosal damage induced by
      OH. radicals. The findings indicate the potential role of cationized enzymes in
      the local protection of the intestinal epithelium against pathological processes
      associated with oxidative stress.

PMID- 8308715
TI  - Controlled-release isosorbide dinitrate pellets. Part I: Design and evaluation of
      controlled-release capsule dosage form.
AB  - Design and evaluation of 8-h controlled-release isosorbide dinitrate capsules
      representing 20.0 and 40.0 mg of the drug are described. The formulation conforms
      to the total drug incorporated in the dosage form. In vitro dissolution studies
      indicate that the formulations behave as controlled-release dosage forms. Studies
      of storage at 30 +/- 2 and 40 +/- 2 degrees C at relative humidities of 72.0 and
      90.0%, respectively, indicate that both temperature and humidity accelerate the
      degradation of the formulation. These results indicate the need of controlled
      packaging conditions during manufacture of these capsules.

PMID- 8308716
TI  - Controlled-release isosorbide dinitrate pellets. Part II: In vivo studies.
AB  - Isosorbide dinitrate (ISDN) capsules containing 20.0 and 40.0 mg of the drug
      (reported earlier in Part I of this series) were evaluated in vivo in eight
      healthy volunteers in a double-blind study with marketed sustained-release
      preparations containing 20.0 and 40.0 mg of ISDN. The results were normalized by
      administering placebo and four conventional ISDN tablets, each containing 5.0 mg
      of ISDN, to the same group of volunteers in a separate study. The blood pressure
      of the volunteers was monitored for 8 h. The results indicate that the capsules
      prepared in the laboratory with the new formulation gave controlled release when
      compared with the respective marketed SR product.

PMID- 8308717
TI  - Estimation of partition ratio when the value is much smaller than the initial
      substrate/enzyme concentration ratio in a suicide enzyme system.

PMID- 8308718
TI  - Estimation of absorption rate constant in a one-compartment model with the
      profile of the bioavailable dose eliminated as a function of multiples of half
      life.

PMID- 8308719
TI  - GABAB receptor modulation of Ca2+ currents in rat sensory neurones by the G
      protein G(0): antisense oligonucleotide studies.
AB  - 1. Calcium channel currents (IBa) were recorded in cultured dorsal root ganglion
      neurones (DRGs), 24-32 h after microinjection with 20-mer phosphorothioate
      antisense oligonucleotides complementary either to a G alpha o or a G alpha i
      unique sequence, or with a nonsense sequence. 2. The ability of the GABAB agonist
      (-)-baclofen (50 microM) to inhibit IBa was examined. The maximum peak current
      was inhibited by 35.3 +/- 4.0% (n = 11) in control non-injected cells, and by
      38.1 +/- 2.6% (n = 11) and 34.8 +/- 4.2% (n = 5) in nonsense- and G alpha i
      oligonucleotide-injected cells. Following G alpha o oligonucleotide injection, (
      )-baclofen inhibited IBa by 21.0 +/- 3.2% (n = 19). 3. Confocal
      immunocytochemical localization of G alpha o showed prominent staining at the
      plasma membrane in control DRGs, and this was also present in G alpha i and
      nonsense oligonucleotide-injected cells. The G alpha o staining at the plasma
      membrane was reduced by 76% in G alpha o oligonucleotide-injected cells. In
      contrast, confocal immunocytochemical localization of G alpha i showed
      immunostaining in the membrane and cytoplasm of control, G alpha o- and nonsense
      injected DRGs, whereas this was depleted by 68% in G alpha i oligonucleotide
      injected cells. 4. These results indicate that the GABAB receptor couples to
      voltage-sensitive calcium channels via the G protein G(o) and not Gi, and that
      antisense oligonucleotides can be used to deplete G proteins in DRGs.

PMID- 8308720
TI  - The effects of low calcium on the voltage-dependent conductances involved in
      tuning of turtle hair cells.
AB  - 1. The voltage-dependent conductances of turtle cochlear hair cells of known
      resonant frequency were characterized by tight-seal, whole-cell recording during
      superfusion with solutions containing normal (2.8 mM) and reduced (0.1-10 microM)
      Ca2+. 2. In 1 microM Ca2+, the current flowing through the voltage-dependent Ca2+
      channels was increased roughly fivefold and had a reversal potential near 0 mV.
      This observation may be explained by the Ca2+ channels becoming non-selectively
      permeable to monovalent cations in low-Ca2+ solutions. Lowering the Ca2+ further
      to 0.1 microM produced little increase in the current. 3. The size of the non
      selective current increased systematically with the resonant frequency of the
      hair cell over the range from 10 to 320 Hz. This suggests that hair cells tuned
      to higher frequencies contain more voltage-dependent Ca2+ channels. 4. There was
      a good correlation between the amplitudes of the non-selective current and the K+
      current which underlies electrical tuning of these hair cells. The amplitude of
      the K+ current also increased systematically with resonant frequency. 5. In cells
      with resonant frequencies between 120 and 320 Hz, the K+ current was completely
      abolished in 1 microM Ca2+, consistent with prior evidence that this current
      flows through Ca2+ activated K+ channels. In a majority of cells tuned between 50
      and 120 Hz, the K+ current was incompletely blocked in 1 microM Ca2+, but was
      eliminated in 0.1 microM Ca2+. In all hair cells the K+ current was abolished by
      25 mM tetraethylammonium chloride. 6. In cells tuned to 10-20 Hz, the K+ current
      was not substantially diminished even in 0.1 microM Ca2+, which argues that it
      may not be Ca2+ activated. 7. In cells tuned to frequencies above 100 Hz, the K+
      current could still be evoked by depolarization during superfusion with 10 microM
      Ca2+. However, its half-activation voltage was shifted to more depolarized levels
      and its maximum amplitude was systematically reduced with increasing resonant
      frequency. 8. These observations are consistent with the notion that in cells
      tuned to more than 50 Hz, there is a fixed ratio of the number of voltage
      dependent Ca2+ channels to Ca(2+)-activated K+ channels, the numbers of each
      increasing in proportion to resonant frequency. The results also provide indirect
      evidence that the Ca(2+)-activated K+ channels in cells tuned to higher
      frequencies may be less sensitive to intracellular Ca2+.

PMID- 8308721
TI  - The frequency content of common synaptic inputs to motoneurones studied during
      voluntary isometric contraction in man.
AB  - 1. The discharges of pairs of individual motor units were recorded from intrinsic
      hand muscles in man. Single motor unit recordings were obtained either when both
      members of the motor unit pair were within first dorsal interosseous muscle
      (1DI:1DI recordings) or where one motor unit was within 1DI and the other in
      second dorsal interosseous muscle (1DI:2DI recordings). The pairs of motor unit
      spike trains were cross-correlated in the time domain and the results compared to
      those of coherence analysis performed on the same spike train data. Central peaks
      were present in the cross-intensity functions, indicating the presence of common
      synaptic input to the motoneurone pair. Coherence analysis of these data
      indicated significant association between motor unit firing in the frequency
      ranges 1-12 and 16-32 Hz. 2. Analysis of sequential non-overlapping segments of
      data recorded from individual motor unit pairs, demonstrated that both the
      central cross-intensity peak and coherence in the frequency bands 1-12 and 16-32
      Hz were consistent features throughout a long recording. In these sequential
      recordings, the size of the central cross-intensity peak and the maximal value of
      coherence in the frequency band 16-32 Hz covaried from segment to segment.
      Analysis of the entire population of motor unit pairs confirmed a positive
      relationship between the magnitude of peak coherence and the size of the central
      cross-intensity peak. 3. Voluntary sinusoidal co-modulation of the firing rates
      of pairs of individual motor units recorded from within 1DI was found to produce
      significant values of coherence corresponding to the frequency of the common
      modulation. However, firing rate co-modulation was not found to affect either the
      size of the central cross-intensity peak or the maximum value of coherence in the
      frequency band 16-32 Hz. 4. Pairs of single motor units were recorded from within
      1DI and biceps brachii muscles of healthy subjects. The number and size of the
      central cross-intensity peaks and coherence peaks detected were compared for the
      two muscles. The incidence and size of central cross-intensity peaks and the
      incidence and magnitude of 16-32 Hz coherence peaks were both found to be greater
      for 1DI recordings when compared to biceps brachii recordings. 5. Single motor
      unit recordings were made from the intrinsic hand muscles of a patient with
      severe peripheral deafferentation. Time- and frequency-domain analysis of these
      recordings revealed cross-intensity peaks and frequency bands of coherence
      similar to those seen in healthy subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8308722
TI  - Human sodium channel myotonia: slowed channel inactivation due to substitutions
      for a glycine within the III-IV linker.
AB  - 1. Three families with a form of myotonia (muscle stiffness due to membrane
      hyperexcitability) clinically distinct from previously classified myotonias were
      examined. The severity of the disease greatly differed among the families. 2.
      Three dominant point mutations were discovered at the same nucleotide position of
      the SCN4A gene encoding the adult skeletal muscle Na+ channel alpha-subunit. They
      predict the substitution of either glutamic acid, valine or alanine for
      glycine1306, a highly conserved residue within the supposed inactivation gate.
      Additional SCN4A mutations were excluded. 3. Electrophysiological studies were
      performed on biopsied muscle specimens obtained for each mutation. Patch clamp
      recordings on sarcolemmal blebs revealed an increase in the time constant of fast
      Na+ channel inactivation, tau h, and in late channel openings as compared to
      normal controls. tau h was increased from 1.2 to 1.6-2.1 ms and the average late
      currents from 0.4 to 1-6% of the peak early current. 4. Intracellular recordings
      on resealed fibre segments revealed an abnormal tetrodotoxin-sensitive steady
      state inward current, and repetitive action potentials. Since K+ and Cl-
      conductances were normal, only the increase in the number of non-inactivating Na+
      channels has to be responsible for the membrane hyperexcitability. 5. Length,
      ramification and charge of the side-chains of the substitutions correlated well
      with the Na+ channel dysfunction and the severity of myotonia, with alanine as
      the most benign and glutamic acid as the substitution with a major steric effect.
      6. Our electrophysiological and molecular genetic studies strongly suggest that
      these Na+ channel mutations cause myotonia. The naturally occurring mutants
      allowed us to gain further insight into the mechanism of Na+ channel
      inactivation.

PMID- 8308723
TI  - Power production and working capacity of rabbit tibialis anterior muscles after
      chronic electrical stimulation at 10 Hz.
AB  - 1. The muscles of the distal anterior compartment of the left hindlimb of rabbits
      were subjected to continuous indirect electrical stimulation at 10 Hz for periods
      of up to 12 weeks by means of an implantable stimulator. 2. The maximum
      shortening velocity (Vmax) and the velocity for maximum power production in
      single contractions (Vopt) were reduced to 42% and 32% of control values
      respectively after 12 weeks of stimulation. The rate of change of these
      parameters was greatest between the second and sixth week of stimulation. These
      changes, it is suggested, reflect the documented time course of the replacement
      of fast with slow isoforms of myosin. 3. The reductions in force production and
      speed of the stimulated muscles combined to produce a marked, progressive decline
      in the maximum power produced in single contractions. After 8 weeks of
      stimulation, the maximum power output had fallen to less than 10% of the control
      value. 4. The fatigue resistance of the stimulated and control muscles was tested
      over several hours of cyclical shortening contractions designed to elicit an
      initial power output of 10 W kg-1 with the muscles set to contract at Vopt. This
      level of work output represented about 1.6% (control) and 25% (12-week
      stimulated) of the absolute maximum power output achieved during single
      contractions. 5. Despite the large reduction in the maximum power output of
      single contractions, the stimulated muscles showed less than 10% reduction in
      their power output during the fatigue tests over periods of up to 7 h. The
      control muscles showed a 70% reduction over the same period. There was no
      difference in the fatigue resistance under this protocol between muscles
      stimulated for 2 weeks and those stimulated for longer periods. Transformation of
      myosin isoforms, which is known to occur later than 2 weeks after the start of
      stimulation, is not necessary for the induction of this degree of fatigue
      resistance.

PMID- 8308724
TI  - Characteristics of multiple voltage-activated K+ currents in acutely dissociated
      chick ciliary ganglion neurones.
AB  - 1. The properties of voltage-activated K+ currents were examined using whole-cell
      recording techniques in acutely isolated chick ciliary ganglion neurones. 2.
      Application of depolarizing voltage pulses from a holding potential of -60 mV
      evoked sustained outward currents that inactivated with time constants of
      hundreds of milliseconds (IDR). Bath application of 10 mM tetraethylammonium
      (TEA) caused a 70-90% reduction of IDR. Application of depolarizing voltage steps
      from a holding potential of -120 mV revealed a second class of TEA-resistant
      outward currents. These currents activated quickly but inactivated completely
      within tens of milliseconds (IA). IA activated at more negative command
      potentials than IDR. However, IDR exhibited a steeper voltage dependence of
      activation than IA. 3. The midpoint of the steady-state inactivation curve of IA
      was between -95 and -110 mV. By contrast the midpoint of the steady-state
      inactivation curve of IDR was between -80 and -90 mV. It was not possible to
      produce a complete inactivation of IDR using prepulses of up to 2 s duration. 4.
      The time course of IA inactivation could only be fitted with double-exponential
      curves with time constants of 5-18 ms and 30-60 ms at membrane potentials
      positive to -30 mV. The inactivation of IA was slower at more positive membrane
      potentials because of a greater contribution of the long time constant. The
      individual time constants were not markedly voltage dependent. 5. Bath
      application of 5 mM 4-aminopyridine (4-AP) caused a 70-100% block of IA whereas 1
      mM 4-AP was ineffective. Bath application of 560 nM alpha-dendrotoxin (DTX)
      produced a 50-70% reduction of IA, but application of 280 nM DTX had no effect on
      IA. 6. Application of 1 mM 4-AP produced a reversible 55-80% block of IDR
      measured at the end of a 500 ms depolarizing pulse. The 4-AP-sensitive components
      of IDR activated rapidly and exhibited a gradual inactivation with continued
      depolarization. The 4-AP-resistant components of IDR activated much more slowly
      and showed very little tendency to inactivate. Significant blockade of IDR was
      produced by 10 microM 4-AP. 7. The decay of IDR tail currents could only be
      fitted with double exponential curves with time constants of 3-6 and 40-60 ms,
      respectively. The fast and slow components of the tail currents behaved
      independently with respect to the duration of the depolarizing voltage step. 8.
      Application of 1 mM 4-AP eliminated the fast, but not the slow component of IDR
      tail currents.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8308725
TI  - Thyroliberin-induced changes in the fluorescence of a membrane probe in
      individual bovine anterior pituitary cells.
AB  - 1. We have investigated the use of TMA-DPH (1-[4-(trimethylammonio) phenyl]-6
      phenylhexa-1,3,5-triene) as an indicator of exocytosis in individual bovine
      anterior pituitary cells using microfluorimetric imaging. 2. TMA-DPH was
      photolabile in artificial and cell membranes. In cells incubated in TMA-DPH the
      distribution of fluorescence depended both on the incubation time and the
      illumination schedule. If the dye was added while the cells were subjected to
      repeated cycles of 0.36 s light intermittent with 1-15 s dark, the fluorescence
      of the peripheral annulus and the central region of individual cells rose in
      parallel and reached a steady state within 200 s; the annulus was always brighter
      than the central region. However, using long intervening dark periods (200 s),
      the central region continued to incorporate dye after the annulus had reached a
      plateau. 3. When the cells were loaded with TMA-DPH using intermittent light with
      short dark periods, the dye washed out of the central region and the annulus in
      parallel when external dye was removed. However, if the cells had been loaded
      using long dark periods, the dye was washed out of the central region more slowly
      than from the annulus. 4. When cells were incubated in TMA-DPH in the dark for 1
      min and then exposed to constant illumination in the presence of external dye,
      the fluorescence of the central region and the annulus both decayed in parallel
      to a new steady state. If the cells were incubated in TMA-DPH in the dark for 240
      min the fluorescence from each region fell to a steady state but the falls were
      larger and were not in parallel. 5. We suggest that TMA-DPH fluorescence was
      derived from plasma membrane-associated and internalized dye and that the amount
      of fluorescence from the latter varied because TMA-DPH was photobleached. Thus,
      when illumination was interrupted by short dark intervals, annular fluorescence
      was high compared to central fluorescence because bleached dye in the plasma
      membrane was rapidly replaced by unbleached dye from the medium. However, long
      dark intervals permitted the dye to be internalized before it was bleached and
      fluorescence was therefore also present in central regions. 6. The total cell
      fluorescence, observed using 15 s dark intervals, was increased 5-40% (in single
      cells) in a dose-dependent fashion by addition of TRH (tripeptide thyrotrophin
      releasing hormone; 1-200 nM).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8308726
TI  - Characterization of the outward rectifying potassium channel in a novel mouse
      intestinal smooth muscle cell preparation.
AB  - 1. The outward rectifying K+ conductance and underlying single channel behaviour
      in mouse small intestine (MSI) smooth muscle cells was studied using
      microelectrode impalement and the patch clamp technique. 2. At 37 degrees C,
      smooth muscle cells in MSI explants had a resting membrane potential around -65
      mV and showed spontaneous electrical and mechanical activity. 3. Under whole-cell
      voltage clamp, depolarization of smooth muscle cells in the explants evoked a
      methoxyverapamil (D600)-sensitive, partially inactivating inward current and a
      non-inactivating outward current. The outward current was also observed in
      enzymatically dispersed cells from neonatal mouse small intestine. 4. The
      reversal potential of the outward current as established in tail current
      experiments was -70.2 mV. Tail currents could be fitted with a single
      exponential, suggesting the participation of only one population of channels. 5.
      The outward current was sensitive to 4-aminopyridine (10(-4) M), Ba2+ (1 mM) and
      to the presence of Cs+ in the pipette, but not to D600 (10(-6) M), or the
      presence of ATP (1 mM) in the pipette. 6. In the cell-attached patch
      configuration, a unitary outward current was observed that showed increased
      activity upon depolarization of the patch. The current-voltage relationship was
      close to linear with a slope conductance of 186 pS. 7. With normal K+ (6 mM) in
      the pipette, the extrapolated reversal potential for the unitary current was
      around -75 mV, while with high K+ (120 mM) the reversal potential was close to 0
      mV. 8. Averaging single channel traces recorded under a depolarizing pulse
      protocol resulted in a trace with similar time characteristics as the outward
      current observed in the whole-cell configuration. 9. The burst behaviour of the
      channel was described by a simple model consisting of two closed states, Cf
      (intraburst closed state) and Cs (interburst closed state) and an open state (O).
      The rate constants in the model showed differential sensitivity to potential
      changes, channel blockade by Ba2+ and equimolar K+ conditions. 10. It was
      concluded that the outward rectifying potassium current in MSI smooth muscle
      cells is mediated by a 186 pS bursting channel. Voltage dependency and Ba2+
      blockade are mainly reflected by changes in the transition rate from the open
      channel state to the interburst closed state.

PMID- 8308727
TI  - Calcium currents and calcium-dependent potassium currents in mammalian medullary
      respiratory neurones.
AB  - 1. Respiratory neurons of mammals are rhythmically active because their membrane
      potential fluctuates periodically over a voltage range of -70 to -55 mV. These
      respiratory drive potentials lead to periodic discharges of bursts of action
      potentials lasting for 1-2 s. The neuronal processes stabilizing this rhythmic
      activity involve excitatory and inhibitory synaptic processes that interact with
      specific membrane properties of the postsynaptic neurones. In the present
      experiments, performed on dorsal and ventral groups of respiratory neurones under
      in vivo and in vitro conditions, we verified the modulating feature of such
      intrinsic neuronal properties. 2. Intrinsic neuronal properties involve Ca2+
      mechanisms that lead to intracellular Ca2+ accumulation, and consequently to
      activation of Ca(2+)-dependent K+ currents. 3. Blockade of intracellular Ca2+
      accumulation significantly changed the amplitude and pattern of respiratory drive
      potentials, and blocked initial hyperpolarizing shifts of the membrane potential
      following each period of synaptic activation. 4. The data demonstrate that
      postsynaptic activities and action potential discharges activate low and high
      voltage-activated Ca2+ currents leading to intracellular Ca2+ accumulation and to
      activation of Ca(2+)-dependent K+ currents that significantly modulate the
      voltage response of medullary respiratory neurones to on-going synaptic
      activation. These intrinsic membrane properties also seem to be involved in the
      processes controlling termination of rhythmic burst discharges.

PMID- 8308728
TI  - The influence of thermoregulatory mechanisms on post-exercise hypotension in
      humans.
AB  - 1. To examine the influence of the rate of heat loss on the magnitude of post
      exercise hypotension, subjects were exposed to three different environmental
      conditions during recovery from bicycle exercise. 2. When subjects recovered in
      warm conditions both core temperature (measured in the external auditory meatus)
      and mean skin temperature were significantly elevated 60 min after the cessation
      of exercise. This attenuation of heat loss was associated with a significant
      reduction in post-exercise mean arterial pressure. 3. In contrast, when subjects
      recovered in neutral or cool conditions both core temperature and mean arterial
      pressure had returned to baseline levels 60 min after exercise. 4. These results
      indicate that persistence of peripheral vasodilatation during recovery from
      exercise, and therefore the magnitude of post-exercise hypotension, is dependent
      upon thermoregulatory-induced changes in skin blood flow.

PMID- 8308729
TI  - Uniform olivocerebellar conduction time underlies Purkinje cell complex spike
      synchronicity in the rat cerebellum.
AB  - 1. The issue of isochronicity of olivocerebellar fibre conduction time as a basis
      for synchronizing complex spike activity in cerebellar Purkinje cells has been
      addressed by latency measurement, multiple-electrode recording and Phaseolus
      vulgaris leucoagglutinin (PHA-L) tracing of climbing fibres in the adult rat. 2.
      The conduction time of the olivocerebellar fibres was measured by recording
      Purkinje cell complex spike (CS) responses from various areas of the cerebellum.
      The CSs were evoked by stimulating the olivocerebellar fibres near the inferior
      olive. In spite of a difference in length, as determined directly by light
      microscopy, the conduction times of different climbing fibres were quite uniform,
      3.98 +/- 0.36 ms (mean +/- S.D., n = 660). 3. Multiple-electrode recording of
      spontaneous Purkinje cell CS activity was employed to study the spatial extent of
      CS synchronicity in the cerebellar cortex. Recordings of CS were obtained from
      Purkinje cells located on the surface and along the walls of lobule crus 2a. The
      rostrocaudal band-like distribution of simultaneous (within 1 ms) CS activity in
      Purkinje cells extended down the sides of the cerebellar folia to the deepest
      areas recorded (1.6-2.6 mm deep). As shown in previous experiments, the
      distribution of simultaneous CS activity did not extend significantly (500
      microns) in the mediolateral axis of the cerebellar cortex. 4. In two animals a
      detailed determination of the length of the olivocerebellar fibre bundles was
      performed by staining the fibres with PHA-L injected into the contralateral
      inferior olive. This measurement included fibre bundles terminating in twenty-six
      different areas, ranging from the tops of the various folia to the bottoms of the
      fissures in both the hemisphere and the vermis. There was a 47.5% difference
      between the length of the longest measured fibre bundle (15.8 mm, terminating in
      lobule 6b, zone A) and the length of the shortest measured fibre bundle (8.3 mm,
      terminating in the cortex at the base of the primary fissure, zone D), after
      correction for tissue shrinkage. To attain an isochronous conduction time the
      conduction velocities for these two fibre bundles were calculated to be 4.22 m/s
      and 2.37 m/s, respectively. 5. By interpolating between measured points a simple
      formula was derived to estimate the average length of olivocerebellar fibres
      terminating in any given area of the cerebellar cortex, excluding the
      paraflocculus, the flocculus and the most lateral regions of the hemisphere. 6.
      We investigated the most likely mechanisms by which conduction velocity
      variations with length could result in global isochronicity.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8308730
TI  - Electrophysiological properties of cat reticular thalamic neurones in vivo.
AB  - 1. The electrophysiological properties of neurones of the reticular thalamic (RE)
      nucleus were studied in acutely prepared cats under urethane anaesthesia. 2. Two
      main types of neuronal firing were recorded. At the resting membrane potential (
      60 to -65 mV) tonic repetitive firing was elicited when the cell was activated
      synaptically or by current injection. From membrane potentials more negative than
      -75 mV, synaptic or direct stimulation generated a burst of action potentials. 3.
      The burst of RE cells consisted of a discharge of four to eight spikes riding on
      a slowly growing and decaying depolarization. The discharge rate during the burst
      showed a characteristic increase, followed by a decrease in frequency. 4. The
      burst response behaved as a graded phenomenon, as its magnitude was modulated by
      changing the intensity of the synaptic volley or the intensity of the injected
      current. 5. Spike-like small potentials presumably of dendritic origin occurred
      spontaneously and were triggered by synaptic or direct stimulation. They were all
      or-none, voltage-dependent events. We postulate that these spikes originate in
      several hot spots in the dendritic arbor, with no reciprocal refractoriness and
      may generate multi-component depolarizations at the somatic level. 6. Excitatory
      postsynaptic potentials (EPSPs) evoked by internal capsule stimulation consisted
      of two components, the late one being blocked by hyperpolarization. Such compound
      EPSPs were followed by a period of decreased excitability during which a second
      response was diminished in amplitude. 7. A series of depolarizing waves at the
      frequency range of spindle oscillations was triggered by internal capsule
      stimulation. The individual depolarizing waves constituting the spindle
      oscillation gradually decreased in amplitude when decreasing the intensity of the
      stimulation. 8. These results, showing that RE cells are endowed with an
      excitable dendritic tree and a graded bursting behaviour, support the proposed
      role of RE nucleus as the generator and synchronizer of spindle rhythmicity.

PMID- 8308731
TI  - Voltage-dependent block by internal Ca2+ ions of inwardly rectifying K+ channels
      in guinea-pig ventricular cells.
AB  - 1. The block of the inwardly rectifying K+ channel by intracellular Ca2+ was
      studied in guinea-pig ventricular cells. 2. Single-channel currents through the
      inwardly rectifying K+ channel were recorded in the inside-out configuration at
      150 mM external and internal K+. Internal Ca2+, at a concentration of 0.4-10
      microM, induced subconductance levels with one-third and two-thirds of the
      unitary amplitude in the outward currents without affecting the inward currents.
      3. Occupancy at each sublevel was estimated from the amplitude histogram which
      showed four equally spaced peaks in the presence of internal Ca2+. At different
      degrees of blockade, the distribution of the current levels showed a reasonable
      agreement with the binomial theorem. 4. The outward mean open-channel currents
      were measured at different Ca2+ concentrations and voltages. The current-voltage
      relation rectified inwardly in the presence of internal Ca2+ in a concentration
      dependent manner. 5. The outward mean open-channel currents were normalized to
      unitary amplitudes in the absence of Ca2+. The normalized current-Ca2+
      concentration curve was fitted by saturation kinetics with a Hill coefficient of
      1 at each voltage. The voltage dependence of the dissociation constants gives the
      value for the fractional electrical distance of the Ca2+ binding site of 0.7. 6.
      The dwell times in each substrate were distributed exponentially. On the
      assumption that the inwardly rectifying K+ channel of cardiac cells is composed
      of three identical conducting subunits and each subunit is blocked by Ca2+
      independently, the blocking (mu) and unblocking (lambda) rates were calculated.
      The value of mu increased with higher Ca2+ concentrations or larger
      depolarizations, while lambda was independent of Ca2+ and decreased with larger
      depolarization. 7. It is thus concluded that internal Ca2+ produces a voltage
      dependent block of the channel to cause inward rectification although the
      blocking effect is less potent than that of Mg2+. The substate behaviour seen
      with internal Ca2+ supports the triple-barrelled structure of the cardiac
      inwardly rectifying K+ channel.

PMID- 8308732
TI  - Effects of ryanodine on the properties of Ca2+ release from the sarcoplasmic
      reticulum in skinned skeletal muscle fibres of the frog.
AB  - 1. We studied the effects of ryanodine on the functions of the sarcoplasmic
      reticulum (SR) in skinned muscle fibres from Xenopus laevis. 2. Ryanodine
      treatment decreased the Ca2+ uptake capacity of the SR in a fixed Ca2+ loading
      condition. The extent of the decrease in the SR Ca2+ uptake capacity was closely
      correlated with the activity of the Ca(2+)-induced Ca2+ release (CICR) during the
      ryanodine treatment. This suggests, in agreement with the previous biochemical
      results, that ryanodine acts on the CICR channels when they are open. 3. The rate
      of Ca2+ leakage from the SR increased after ryanodine treatment. However, the
      leakage rate constants were independent of the degree of the loss of SR Ca2+
      uptake capacity by the ryanodine treatment. This is inconsistent with the notion
      that the SR is a single uniform compartment and that the decline in the SR Ca2+
      uptake capacity is a result of the increase in the Ca2+ leakage. 4. Partial
      recovery of the Ca2+ uptake capacity of the ryanodine-treated SR was observed
      when Ca2+ loading was carried out in the presence of 10 mM procaine. This
      indicates that procaine partially blocks the open-locked channels. 5. After Ca2+
      loading in the presence of procaine, removal of procaine induced a rapid release
      of Ca2+ from the SR through the open-locked channels. This rapid release was
      dependent both on the adenine nucleotide concentration and on the Ca2+
      concentration. Thus, the 'open-locked' CICR channels are still regulated by Ca2+
      and adenine nucleotides.

PMID- 8308733
TI  - Membrane potential modulates inositol 1,4,5-trisphosphate-mediated Ca2+
      transients in guinea-pig coronary myocytes.
AB  - 1. Vascular smooth muscle cells were isolated from the coronary artery of the
      guinea-pig. At 2.5 mM [Ca2+]o and 36 degrees C, whole cell membrane currents were
      recorded under voltage-clamp and the concentration of ionized calcium in the
      cytoplasm ([Ca2+]i) was monitored by indo-1 fluorescence. 2. At -60 mV, [Ca2+]i
      was 143 +/- 36 mM (mean +/- S.D.) and was insensitive to clamp steps to +100 mV.
      During 1 min application of acetylcholine (ACh, 10 microM) [Ca2+]i increased
      within approximately 2 s to 1480 +/- 250 nM. During the subsequent slow decay,
      [Ca2+]i was transiently increased by depolarizing clamp steps and decreased
      during hyperpolarizing steps. [Ca2+]i transients in response to caffeine (10 mM)
      could not be modulated by voltage steps. The results suggest that modulation of
      [Ca2+]i by membrane potential involves inositol 1,4,5-trisphosphate
      (Ins(1,4,5)P3)-induced Ca2+ release (IICR). 3. Modulation of IICR by membrane
      potential did not depend on sarcolemmal Ca2+ fluxes; it persisted after block of
      sarcolemmal Ca2+ fluxes with 3 mM lanthanum or after a change to nominally Ca(2+)
      free bathing solutions. 4. Modulation of [Ca2+]i by membrane potential was
      recorded during cell dialysis of 50 microM GTP-gamma-S in the absence of ACh.
      Cell dialysis of exogenous Ins(1,4,5)P3 (50 or 100 microM) did not mimic the
      effects. The sensitivity of [Ca2+]i to depolarizing clamp steps was also induced
      by cell dialysis of lithium ions which, presumably, inhibited the breakdown of
      Ins(1,4,5)P3. The results are compatible with the idea that the membrane
      potential modulates the liberation of Ins(1,4,5)P3. 5. Modulation of IICR by
      membrane potential is discussed as a new mechanism that contributes to the
      regulation of activator calcium and to the modulation of contraction in vascular
      smooth muscle cells.

PMID- 8308734
TI  - Calcium and potassium currents in ventricular myocytes isolated from diabetic
      rats.
AB  - 1. The whole-cell voltage-clamp technique was applied to ventricular myocytes
      isolated from normal and streptozotocin-induced diabetic rat hearts to
      investigate the contribution of the calcium current and of the calcium
      independent potassium currents to diabetes-induced alterations of the action
      potential. 2. In single calcium-tolerant isolated myocytes diabetes induced a
      lengthening of the action potential similar to that previously described in
      intact ventricular muscles. 3. Only L-type calcium current was present both in
      normal and diabetic cells. Inactivation of ICa was described in both preparations
      by two exponentials, whose time constants were not modified by diabetes. 4.
      Calcium current density-voltage relationships and steady-state inactivation
      curves were not significantly affected by diabetes. 5. Potassium background
      inward rectifier current was not modified by diabetes. 6. Calcium-independent
      outward potassium current inactivated, in both cell types, according to a
      biexponential process whose time constants were not affected by diabetes. 7. The
      transient outward potassium current density was significantly reduced by diabetes
      whereas neither the voltage dependence of the inactivation nor the time
      dependence of recovery from inactivation was modified. 8. A 4-aminopyridine
      insensitive potassium current was also reduced by diabetes. 9. Our results show
      that in isolated ventricular myocytes the lengthening of the action potential
      induced by diabetes results mainly from a decrease of the transmembrane calcium
      independent potassium permeability.

PMID- 8308735
TI  - Axonal projections and synaptic connections of C5 segment expiratory
      interneurones in the cat.
AB  - 1. Respiratory interneurones in the C4-C6 segments of the spinal cord have only
      recently been described; until now their projections and connections were not
      known. We investigated expiratory interneurones in the C5 spinal segment, using
      antidromic mapping to trace their projections and spike-triggered averaging to
      test their synaptic connections with phrenic motoneurones. 2. A total of seventy
      expiratory interneurones were recorded in nineteen cats anaesthetized with
      pentobarbitone, paralysed and ventilated. The interneurones were found scattered
      dorsomedial to the phrenic motor nucleus, with discharge patterns of a constant
      (66%), augmenting (24%) or decrementing (10%) type. 3. Interneurone axons were
      found in the ipsilateral ventrolateral funiculus using antidromic activation at
      thresholds < 20 microA. The axons of eighteen of thirty-three interneurones
      tested (55%) were found to extend to the rostral part of the C6 segment,
      seventeen of thirty-three (52%) to the caudal part of the C6 segment and ten of
      nineteen (53%) to the rostral part of the C7 segment. 4. Axon collaterals for
      thirteen of thirty-three interneurones (39%) were found in the ipsilateral half
      of the C6 segment, with their endings near the phrenic motor nucleus. In three
      cases two collaterals were found. None of the interneurones had projections in
      the contralateral halves of the C5 or C6 segments. 5. In a separate group of
      thirty-four expiratory interneurones, antidromic mapping was used to find an axon
      collateral in the C6 segment prior to spike-triggered averaging. Eleven of these
      interneurones had collaterals (32%) and were subsequently tested for synaptic
      connections to thirty-two phrenic motoneurones. In three separate instances (9%),
      inhibitory postsynaptic potentials were observed. Amplitudes, fall times and half
      amplitude widths of the inhibitory postsynaptic potentials were 6.7, 10.4 and
      10.6 microV; 0.3, 0.5 and 0.7 ms and 0.6, 1.6 and 3.3 ms respectively. 6. We
      conclude: (i) there is a population of expiratory interneurones in the C5
      segment, located predominantly dorsomedial to the phrenic motor nucleus; (ii) at
      least one-half of these interneurones have ipsilateral intersegmental projections
      to the C6 segment and (iii) although synaptic connections from expiratory
      interneurones in the C5 segment to phrenic motoneurones in the C6 segment may be
      rare, the observed inhibitory postsynaptic potentials had fall times and
      latencies commensurate with monosynaptic connections.

PMID- 8308736
TI  - Electrical coupling of circular muscle to longitudinal muscle and interstitial
      cells of Cajal in canine colon.
AB  - 1. Electrical communication between circular muscle, longitudinal muscle and
      interstitial cells of Cajal (ICC) was investigated; the hypothesis was tested
      that the resting membrane potential (RMP) gradient in the circular muscle of
      canine colon is caused by electrical coupling to neighbouring cells. 2. Isolated
      longitudinal muscle exhibited spike-like action potentials at a RMP of -45 mV
      with a frequency and amplitude of 20 cycles/min and 12 mV, respectively. 3. The
      circular muscle (CM), devoid of longitudinal muscle, myenteric plexus and
      submuscular ICC-smooth-muscle network, was electrically quiescent at a uniform
      RMP of -62 mV across the entire circular muscle layer. 4. Preparations consisting
      of only the submuscular ICC network and a few adjacent layers of circular muscle
      cells exhibited slow wave-type action potentials at a RMP of about -80 mV. 5. In
      ICC-CM preparations, consisting of the submuscular ICC network and circular
      muscle, a RMP gradient of 10 mV was observed near the submucosal border, whereas
      the RMP was constant at -62 mV in the myenteric half of the circular muscle. 6.
      In full thickness (FT) preparations, a RMP gradient of 23 mV was observed. The
      RMP decreased gradually from -71 mV at the submucosal border to -48 mV at the
      myenteric border of the circular muscle. 7. Coupling of longitudinal muscle to
      circular muscle caused circular muscle cells at the myenteric surface to
      depolarize by 14 mV and longitudinal muscle cells to hyperpolarize by 3 mV. 8. In
      the ICC-CM preparations, the slow wave amplitudes did not decay exponentially
      away from the ICC network indicating that slow waves propagated actively into the
      circular muscle; in the FT preparations there was an apparent exponential decay
      but this was due to the RMP gradient. 9. Spike-like action potentials (SLAPs)
      superimposed on the plateau phase of slow waves did not decay exponentially away
      from the myenteric border suggesting that SLAPs were generated within the
      circular muscle layer. 10. In summary, circular muscle cells possess a uniform
      intrinsic RMP of -62 mV. The RMP gradient in situ is caused by electrical
      coupling of circular muscle cells to longitudinal muscle cells and the
      submuscular network of ICC. In situ, slow wave-type action potentials propagate
      actively into the circular muscle layer, and, dependent on the level of
      excitation, circular muscle cells actively generate spikes.

PMID- 8308737
TI  - A dendritic gain control mechanism in axonless neurons of the locust,
      Schistocerca americana.
AB  - 1. To understand the possible function of active dendritic currents in local
      neurons, the non-linear electrical properties of locust axonless non-spiking
      interneurons were considered in parallel with the properties of graded
      transmitter release from their dendrites. 2. The dendritic membrane of the non
      spiking interneurons was least responsive to an applied or synaptic current at
      potentials between -55 and -45 mV. This is because, at these potentials, the
      input resistance of the dendrites is reduced by the activation of voltage
      dependent K+ conductances. Conversely, the membrane of the non-spiking
      interneurons was most responsive to an applied or synaptic current at potentials
      more negative than -55 mV (where the membrane behaves more or less passively), or
      more positive than -45 mV (where the activation of a Ca2+ current can boost
      depolarizing potentials). 3. The threshold for detectable release at the non
      spiking synapse was around -65 mV. The dynamic gain of the synape (slope of the
      synaptic transfer curve) was maximum around -50 mV. Saturation was observed
      around -40 mV. Synaptic transfer is therefore most efficient at presynaptic
      potentials where the non-spiking dendritic membrane is least responsive to
      incoming signals. 4. The possible consequences of this matching of membrane and
      synaptic non-linearities was studied theoretically, with computer-assisted
      simulations, and experimentally, by recording simultaneously from the dendrites
      of synaptically connected non-spiking interneurons and motoneurons. This precise
      matching of non-linearities was found to have two important consequences: (i) it
      allowed the effective gain of polysynaptic pathways via non-spiking dendrites to
      depend little on the state of the interposed interneuron (linearization) and (ii)
      it optimized coding by preventing undesired over-amplification and synaptic
      saturation.

PMID- 8308738
TI  - The role of vasopressin in the regional vascular responses evoked in the
      spontaneously breathing rat by systemic hypoxia.
AB  - 1. In spontaneously breathing rats anaesthetized with Saffan, we have
      investigated the role of vasopressin in the cardiovascular responses evoked by
      systemic hypoxia (breathing 8 or 6% O2 for 5 min). 2. Breathing 8% O2 evoked an
      increase in respiratory frequency and tidal volume; arterial O2 pressure (Pa,O2)
      fell to 37 mmHg and arterial CO2 pressure (Pa,CO2) fell to 30 mmHg.
      Concomitantly, there was a fall in arterial pressure, tachycardia and increases
      in femoral and renal vascular conductances indicating net vasodilatation in
      skeletal muscle and kidney. The vasopressin V1-receptor antagonist,
      d(CH2)5Tyr(Me)-arginine vasopressin (20 micrograms kg-1 i.v.), had no significant
      effect on the baseline values of any recorded variables, nor on the respiratory
      or blood gas changes evoked by 8% O2. However, it accentuated the fall in
      arterial pressure and the increase in femoral vascular conductance (+22 vs. +77%
      at the 5th minute) produced by 8% O2, but had no significant effect on the
      increase in renal vascular conductance. 3. Breathing 6% O2 evoked qualitatively
      similar responses as 8% O2 but Pa,O2 fell to 33 mmHg and Pa,CO2 fell to 28 mmHg
      and the respiratory and cardiovascular changes tended to be larger than those
      evoked by 8% O2. Again the V1-receptor antagonist accentuated the hypoxia-induced
      fall in arterial pressure and increase in femoral vascular conductance (+5 vs.
      +76% at the 5th minute). 4. Infusion of vasopressin (1.5 ng min-1 kg-1 i.v.) for
      5 min with the aim of producing a plasma concentration comparable to that reached
      during 8% O2, induced a rise in arterial pressure (9%), bradycardia (-5%) and a
      decrease in femoral (-11%) and renal vascular conductance (-4%). 5. These results
      suggest that vasopressin released during hypocapnic hypoxia helps to limit the
      evoked fall in arterial pressure by exerting a vasoconstrictor influence on
      skeletal muscle.

PMID- 8308739
TI  - The influence of vasopressin on the arterioles and venules of skeletal muscle of
      the rat during systemic hypoxia.
AB  - 1. In rats anaesthetized with Saffan, the spinotrapezius muscle was prepared for
      in vivo microscopy. Systemic hypoxia (breathing 8% O2 for 3 min) induced a fall
      in arterial pressure and tachycardia, together with constriction in some
      arterioles and venules of each section of the vascular tree and dilatation in
      others. 2. The vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)-arginine
      vasopressin (20 mg kg-1 I.V.) preferentially attenuated constrictor responses
      induced by hypoxia in both arterioles and venules, but had no significant effect
      on the dilator responses. Analysis of responses in individual sections of the
      vascular tree suggested that the V1-receptor antagonist reduced hypoxia-induced
      constrictor responses in proximal arterioles (> 13 microns diameter) though not
      in terminal arterioles (< 13 microns), but reduced hypoxia-induced constrictor
      responses in both the proximal and distal venules (9-130 microns). 3. Infusion of
      vasopressin at 1.4, 2.8, 5.7 and 11.4 ng min-1 kg-1 i.v. for 3 min, expected to
      produce plasma concentrations within the range 28-228 pg ml-1, evoked rises in
      arterial pressure together with decreases in heart rate. There was also
      vasoconstriction in the proximal arterioles of spinotrapezius that was graded
      with vasopressin concentration (5-35% decrease in diameter). 4. Infusion of
      vasopressin at 1.4 mg min-1 kg-1 i.v. for 3 min with the intention of producing a
      plasma concentration likely to be reached or exceeded during 8% O2, evoked
      constriction of all proximal arterioles, though not of terminal arterioles, and
      constriction of all venous vessels. The magnitude of the constriction induced by
      vasopressin in vessels that dilated during hypoxia was just as great as in those
      that constricted during hypoxia. 5. We propose that vasopressin released during
      systemic hypoxia exerts a constrictor influence upon the proximal arterioles and
      all sections of the venous tree of skeletal muscle. In individual arterioles and
      venules the constrictor influence of vasopressin and catecholamines may be
      overcome by the influence of locally released vasodilator metabolites.

PMID- 8308740
TI  - Differential expression of sodium channels in acutely isolated myelinating and
      non-myelinating Schwann cells of rabbits.
AB  - 1. Single channel recordings were made of voltage-sensitive sodium channels in
      outside-out patches excised from the cell body region of Schwann cells. The cells
      were freshly isolated from sciatic nerves of 10-week-old rabbits and both
      myelinating and non-myelinating Schwann cells were visually identified for
      recordings. 2. Sodium channel activities were observed in approximately 75% of
      patches (n = 41) obtained from cell bodies of non-myelinating Schwann cells. In
      contrast, sodium channels were not observed in patches (n = 78) obtained from
      cell bodies of myelinating Schwann cells. 3. Transection of the sciatic nerves
      and allowing Wallerian degeneration to occur for 5-11 days in vivo prior to
      recording resulted in the appearance of sodium channel activities in
      approximately 30% of the patches (n = 33) obtained from the cell body of the
      myelinating cells. 4. It is interesting that although immunocytochemical and
      saxitoxin binding experiments indicate the clear presence of sodium channels in
      the plasmalemma of myelinating Schwann cells (both at the cell body and at the
      paranodal region), the present study suggests that these channels are absent from
      the soma region of normal myelinating Schwann cells.

PMID- 8308741
TI  - Role of GTP-protein and endothelium in contraction induced by ethanol in pig
      coronary artery.
AB  - 1. We examined the effects of ethanol on the contractility of strips of porcine
      coronary artery, with and without endothelium, and following permeabilization
      with alpha-toxin, and of aortic valvular endothelial cells, in situ. Changes in
      cytosolic Ca2+ concentration ([Ca2+]i) of the coronary artery smooth muscle cells
      and of the valvular endothelial cells were monitored using front-surface
      fluorometry of the calcium indicator dye, fura-2. In permeabilized preparations,
      [Ca2+]i was clamped using 10 mM ethyleneglycol-bis-(beta-aminoethylether)
      N,N,N',N'-tetra ace tic acid (EGTA) and 10 microM A23187 (a calcium ionophore).
      2. The strips without endothelium were placed in normal physiological salt
      solution (normal PSS) in the presence of ethanol (100-1000 mM). There were dose
      dependent increases in [Ca2+]i and a rapid sustained rise in tension. In Ca(2+)
      free PSS, ethanol increased [Ca2+]i and tension, similar to, but much smaller
      than, findings with normal PSS. 3. For a given change in [Ca2+]i induced by
      ethanol, the developed tension was greater than that observed during contractions
      induced by high [K+]o. Thus, the [Ca2+]-tension curve for ethanol was shifted to
      the left of that for high [K+]o. The [Ca2+]-tension curve for the contraction
      induced by ethanol in the absence of extracellular Ca2+ was shifted further to
      the left from that obtained in the presence of [Ca2+]o. 4. The mechanisms
      involved in this Ca(2+)-sensitizing effect of ethanol were investigated using
      alpha-toxin-permeabilized coronary medial strips. Ethanol increased the tension
      development, in a concentration-dependent manner, at a fixed concentration of
      Ca2+ (pCa = 6.3) in the presence of guanosine-5'-triphosphate (GTP), an effect
      antagonized by guanosine-5'-O-(beta-thiodiphosphate) (GDP beta S), a non
      hydrolysable GDP analogue. 5. With intact endothelium, the ethanol-induced
      tension development was markedly reduced, although inhibition in the increase in
      [Ca2+]i was slight. The [Ca2+]-tension relationship of this contraction
      overlapped with that obtained with high [K+]o-induced contraction and was shifted
      to the right from that obtained in the absence of the endothelium. This
      endothelium-dependent reduction of [Ca2+]i and tension induced by ethanol was
      inhibited when the strips were exposed to NG-monomethyl-L-arginine (L-NMMA). 6.
      Ethanol induced a gradual and sustained increase in [Ca2+]i in normal PSS, and a
      transient, concentration-dependent increase in [Ca2+]i in Ca(2+)-free PSS in
      porcine aortic valvular endothelial cells in situ.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8308742
TI  - Mechanism of mu-opioid receptor-mediated presynaptic inhibition in the rat
      hippocampus in vitro.
AB  - 1. The electrophysiological action of the mu-opioid receptor-preferring agonist D
      Ala2, MePhe4, Met(O)5-ol-enkephalin (FK 33-824) on synaptic transmission has been
      studied in area CA3 of organotypic rat hippocampal slice cultures. 2. FK 33-824
      (1 microM) had no effect on the amplitude of pharmacologically isolated N-methyl
      D-aspartate (NMDA) or non-NMDA receptor-mediated EPSPs. 3. FK 33-824 (10 nM to 10
      microM) reduced the amplitude of monosynaptic inhibitory postsynaptic potentials
      (IPSPs) that were elicited in pyramidal cells with local stimulation after
      pharmacological blockade of excitatory amino acid receptors. This effect was
      reversible, dose-dependent, and sensitive to naloxone and the mu-receptor
      antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP). FK 33-824 at 1 microM caused a mean
      reduction in the amplitude of the monosynaptic IPSP of 70%. 4. Neither delta- nor
      kappa-receptor-preferring agonists had any effect on excitatory or inhibitory
      synaptic potentials. 5. The disinhibitory action of FK 33-824 was blocked by
      incubating the cultures with pertussis toxin (500 ng/ml for 48 h) or by
      stimulation of protein kinase C with phorbol 12,13-dibutyrate (PDBu, 0.5 microM).
      6. The depression of monosynaptic IPSPs by FK 33-824 was unaffected by
      extracellular application of the K+ channel blockers Ba2+ or Cs+ (1 mM each). 7.
      FK 33-824 produced a decrease in the frequency of miniature, action potential
      independent, spontaneous inhibitory synaptic currents (mIPSCs) recorded with
      whole-cell voltage-clamp techniques, but did not change their mean amplitude.
      Application of the Ca2+ channel blocker Cd2+ (100 microM) or of nominally Ca(2+)
      free solutions did not alter either the frequency and amplitude of mIPSCs or the
      reduction of mIPSC frequency induced by FK 33-824. 8. The effect of FK 33-824 on
      spontaneous mIPSCs was prevented by naloxone, and by incubation of cultures with
      pertussis toxin. 9. These results indicate that mu-opioid receptors decrease GABA
      release presynaptically by a G protein-mediated inhibition of the vesicular GABA
      release process, and not by changes in axon terminal K+ or Ca2+ conductances that
      are sensitive to extracellular Ba2+, Cs+ or Cd2+.

PMID- 8308743
TI  - ATP modulation of calcium channels in chromaffin cells.
AB  - 1. The effects of externally applied micromolar concentrations of adenosine 5'
      triphosphate (ATP) on Ca2+ currents (ICa) were studied in whole-cell clamped
      adrenaline-secreting chromaffin cells. 2. Ca2+ currents in chromaffin cells
      activated at about -40 mV, reached a maximum at 0 mV and had an apparent reversal
      potential at +50 to +60 mV, indicating the existence of only high voltage
      activated Ca2+ channels. 3. ATP blocked Ca2+ current rapidly, reversibly and in a
      concentration-dependent manner (10(-9)-10(-4) M). 4. ATP did not completely block
      Ca2+ current even at the highest concentrations used (100 microM). The remaining
      component of Ca2+ current was characterized by slower activation and inactivation
      kinetics. 5. ATP blocked ICa even in the presence of nisoldipine and/or omega
      conotoxin GVIA, suggesting that its modulatory role is not specific for L- and/or
      N-type Ca2+ channels. 6. Other adenine nucleotides also blocked the Ca2+ current
      partially. The order of potencies was ATP > or = ADP > AMP >> adenosine,
      indicating that the ATP effects are most probably mediated by a P2-type
      purinergic receptor. 7. Dialysis of the cells with an intracellular solution
      containing 1 mM guanosine 5'-O-thiodiphosphate (GDP-beta-S) or pre-incubation of
      the cells with pertussis toxin (PTX) blocked the inhibitory effects of ATP. 8.
      Intracellular application of the non-hydrolysable GTP analogue guanosine 5'-O-(3'
      thiotriphosphate) (GTP-gamma-S; 50 microM) also decreased ICa in a manner similar
      to that seen for ATP and significantly reduced the ATP inhibitory effect. 9.
      Conditioning pulses to potentials positive to +80 mV partly reversed the
      inhibitory effects of ATP on the Ca2+ current. The prepulse-induced enhancement
      of ICa depended on [GTP]i-related G protein activity such that concentrations
      larger than 200 microM GTP, or GTP-gamma-S (50 microM) were required for
      significant prepulse potentiation of the Ca2+ current, while dialysis with GDP
      beta-S prevented it. 10. We conclude that the ATP, co-released with
      catecholamines in the intact adrenal gland, may inhibit the secretory process by
      down-regulating the Ca2+ channel via a P2-type purinergic receptor coupled to a
      PTX-sensitive G protein.

PMID- 8308744
TI  - A comparison of effect of temperature on phosphorus metabolites, pH and Mg2+ in
      human and ground squirrel red cells.
AB  - 1. 31P NMR spectra were obtained at temperatures ranging from 2 to 30 degrees C
      from freshly drawn human (cold-sensitive) and ground squirrel (cold-tolerant) red
      cells. The concentration of ATP was also determined by luciferin-luciferase assay
      over the same temperature range. 2. The concentration of ATP as determined by NMR
      or by the luciferin-luciferase assay did not change with temperature in either
      species. The absolute concentration of ATP in human cells determined by NMR was
      not significantly different from the total ATP determined enzymatically. 3. The
      concentration of 2,3-diphosphoglycerate was higher and that of pyridine
      nucleotides lower in human than in ground squirrel red cells. This species
      difference was independent of temperature. 4. Intracellular pH, as determined
      from the positions of the NMR peaks of 2- and 3-phosphates of diphosphoglycerate,
      became more alkaline as the temperature was lowered. 5. Free intracellular
      magnesium, determined from the difference in the positions of the peaks for alpha
      and beta-phosphorus of ATP, increased in the ground squirrel red cells and
      decreased in the human red cells with cooling from 30 to 2 degrees C. Total
      magnesium, as determined by atomic emission spectroscopy, did not change with
      temperature in red cells of either species. 6. The intensities of all phosphorus
      metabolite signals from the ground squirrel cells increased with decreasing
      temperature, while those from the human cells were unaffected. Since chemical
      shift anisotropy in the presence of magnesium is a powerful spin-lattice
      relaxation mechanism for phosphates, this is additional evidence for the
      temperature dependence of free magnesium concentration in the ground squirrel
      cells. 7. We conclude that there is no difference in phosphorus metabolites or
      intracellular pH which could account for the differential cold sensitivity in
      human and ground squirrel red cells. We suggest that, in the cold-tolerant red
      cells from the ground squirrel, magnesium is released from binding sites as the
      temperature is lowered. The change in free intracellular Mg2+ may account at
      least in part for the unusually low temperature sensitivity of the Na(+)-K+ pump
      in the red cells of this species.

PMID- 8308745
TI  - Calcium-mediated modulation of N-methyl-D-aspartate (NMDA) responses in cultured
      rat hippocampal neurones.
AB  - 1. Agonist-independent (inactivation) and agonist-induced (desensitization)
      refractory states of N-methyl-D-aspartate (NMDA) receptors were studied on
      cultured rat hippocampal neurones using whole-cell and inside-out patch-clamp
      techniques and a fast perfusion system. 2. Shortly after whole-cell formation,
      application of 100 microM NMDA in the presence of 10 microM glycine and 0.2 mM
      [Ca2+]o induced membrane currents that desensitized by 23%. Repeated application
      of NMDA at 30 s intervals resulted in a progressive increase in the degree and
      rate of onset of NMDA receptor desensitization. 3. Test responses to NMDA
      recorded in the presence of 0.2 mM [Ca2+]o were reversibly inactivated by 60%
      following a train of ten 1 s applications of NMDA delivered at 0.5 Hz in the
      presence of 2 mM [Ca2+]o; similar results were obtained with 2 mM [Sr2+]o and 2
      mM [Ba2+]o. In the presence of Ca2+ or Sr2+, desensitization during the train of
      responses to NMDA increased by 14 and 19% respectively, while with Ba2+ there was
      no increase in desensitization. 4. In the presence of 0.2 mM [Ca2+]o at a holding
      potential of -60 mV, or in the presence of 2 mM [Ca2+]o at a holding potential of
      +50 mV, a train of ten applications of NMDA failed to induce either inactivation
      or an increase in desensitization of test responses to NMDA. These results
      suggest an important role for [Ca2+]o in the induction of both inactivation and
      desensitization of NMDA receptors. 5. Increasing the intracellular calcium
      concentration, [Ca2+]i, via repeated activation of voltage-gated Ca2+ channels,
      resulted in a reversible inactivation of test responses to NMDA by 35% but failed
      to increase desensitization. In neurones dialysed with intracellular solution
      containing 2.5 mM Ca2+ NMDA receptor desensitization was similar to that in
      neurones dialysed with 10 nM Ca2+. 6. Block of NMDA receptor-channels by 2 mM
      [Mg2+]o during the train application of NMDA prevented the induction of both
      inactivation and desensitization. In contrast 3 mM [Mg2+]i was ineffective. 7.
      The magnitude of both inactivation and desensitization of NMDA receptors was not
      affected by intracellular dialysis of ATP, the non-hydrolysable ATP analogue 5'
      adenylylimido-diphosphate (AMP-PNP), different Ca2+ chelators (EGTA or BAPTA),
      the Ca(2+)-activated protease inhibitor (leupeptin), dithiothreitol, or the
      phosphatase inhibitors (okadaic acid and a calcineurin inhibitor). 8. Application
      of 2.5 mM Ca2+ to the cytoplasmic side of inside-out patches induced inactivation
      of NMDA responses similar in magnitude to the inactivation seen in whole-cell
      recording.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8308746
TI  - Long-term modulation of the exercise ventilatory response in goats.
AB  - 1. To test the hypothesis that repeated associations of exercise and increased
      respiratory dead space elicit mechanisms that augment future ventilatory
      responses to exercise alone, experiments were conducted on normal adult goats
      familiarized with experimental procedures. 2. Measurements of ventilation,
      arterial blood gases and CO2 production were made at rest, during mild steady
      state exercise (4 km h-1; 5% grade) and with increased dead space at rest in
      seven goats before and after training. In Series I experiments, training
      consisted of fourteen to twenty exercise trials explicitly paired with increased
      dead space (0.8 l) over 2 days. Increased dead space predominantly represents a
      CO2 chemoreceptor stimulus with only mild hypoxic stimulation. Post-training
      measurements were made 1-6 h and 1 week after training was completed. 3. The same
      goats repeated a slightly modified protocol several months later (Series II; 6
      trials per day for 4 days) to determine if responses were both repeatable and
      reversible, and to investigate training effects on dynamic ventilatory responses
      at the onset of exercise. 4. In Series I experiments, resting minute ventilation
      and breathing frequency were elevated 1-6 h post-training compared to baseline
      (44 and 74% respectively), whereas resting tidal volume decreased (14%). One week
      post-training, resting values had returned to baseline. Series II training had no
      significant effects on resting measurements. 5. Relative to baseline, arterial
      partial pressure of CO2 (Pa,CO2) values decreased significantly more from rest to
      exercise 1-6 h post-training in both Series I (2.7 +/- 0.2 vs. 1.8 +/- 0.9 mmHg)
      and Series II (3.4 +/- 0.6 vs. 2.0 +/- 0.6 mmHg). The exercise ventilatory
      response increased 25-28% 1-6 h post-training (both series), largely due to a
      greater exercise frequency response, but returned to baseline 1 week post
      training. Training had no effect on ventilatory responses to CO2 at rest,
      suggesting that decreases in CO2 chemoreceptor responsiveness did not cause the
      greater exercise ventilatory response. Model estimates indicate that the net
      feedforward exercise ventilatory stimulus was increased 40-50% by training. 6.
      Training had no discernable effects on ventilatory dynamics at the onset of
      exercise. However, post-training differences in Pa,CO2 regulation and ventilation
      were established early in exercise, prior to steady state. 7. Collectively, these
      experiments suggest a previously unsuspected degree of repeatable and reversible
      plasticity in the control system subserving the exercise ventilatory response.
      Such plasticity may contribute to the development of normal exercise hyperpnoea
      and to adaptive responses of the ventilatory control system in adult animals.

PMID- 8308747
TI  - Evidence for active maternal-fetal transport of Na+ across the placenta of the
      anaesthetized rat.
AB  - 1. In order to investigate mechanisms of Na+ transfer, the unidirectional
      maternal-fetal clearance (Kmf) of 22Na+ and of 51Cr-EDTA (a marker of
      paracellular diffusion) was measured across the intact or umbilically or dually
      perfused placenta of the anaesthetized rat. 2. The Kmf of 22Na+ in the intact
      preparation (18.5 +/- 2.7 microliters min-1, mean +/- S.D., n = 105 placentas)
      exceeded that of 51Cr-EDTA in the same experiments (1.4 +/- 0.3 microliters min
      1) by more than ten times, whereas the difference in their diffusion coefficients
      in water was only 2-fold. In the perfused preparations the difference in the Kmf
      values was 6-fold. 3. Assuming that a simple model of paracellular diffusion
      through wide pores was one component of transfer, the Kmf of 51Cr-EDTA and the
      diffusion coefficients were used to calculate a component of 22Na+ clearance
      (Kmf,residual) and of Na+ flux (Jmf,residual) across the perfused placentas which
      could not be accounted for by transfer through the paracellular route. 4.
      Kmf,residual of 22Na+ across the dually perfused placenta was significantly lower
      when temperature was reduced, the temperature quotient (Q10) of the transfer
      being about 2. Kmf,residual was also significantly lower when 0.1 mM ouabain was
      perfused on the fetal side. Jmf,residual exhibited saturation kinetics
      characterized by an apparent Michaelis constant (Km) of 90 mM. Kmf,residual was
      not influenced by 0.5 mM frusemide, 0.5 mM amiloride or by 0.5 mM
      hydrochlorothiazide administered to the maternal side. It was significantly
      increased by 1 mM alanine on the maternal side suggesting that the coupled
      transfer of Na+ and amino acids may contribute significantly to the maternal
      fetal flux of Na+. 5. These observations suggest that most (80%) of the maternal
      fetal flux of Na+ across the rat placenta is effected by active transcellular
      transport. This transport involves passive entry of Na+ into the trophoblast from
      the maternal side by a largely unknown saturable mechanism and active extrusion
      of Na+ from trophoblast to the fetal side by Na(+)-K(+)-ATPase.

PMID- 8308748
TI  - Transport into retina measured by short vascular perfusion in the rat.
AB  - 1. The short duration cerebrovascular perfusion method for measuring permeability
      of the blood-brain barrier has been adapted to measuring transport into the
      retina. 2. The method has been characterized on the one hand by comparing uptakes
      of radiotracers during HCO3(-)-buffered saline perfusion with those occurring
      after intravenous bolus injection of radioisotopes, and on the other by comparing
      uptake into retina with the uptake into frontal cerebral cortex. The mean
      permeability-surface area (PS) products (ml s-1 g-1) for [14C]urea and
      [14C]thiourea in the perfused retina were 1.2 +/- 0.26 x 10(-3) and 2.1 +/- 0.01
      x 10(-3) respectively. The intravenous injection method gave comparable values
      for [14C]urea and [14C]thiourea of 1.6 +/- 0.28 x 10(-3) and 3.24 +/- 0.55 x 10(
      3). The rates of uptake of the hydrophilic solutes were 2- to 7-fold greater than
      in brain. 3. Retinal and choroidal capillary perfusion fluid flow rates were
      measured using a diffusible flow marker ([14C]diazepam) and a particulate
      indicator (15 microns cerium141-labelled microspheres). Results using both flow
      markers confirmed that both capillary networks supplying the retina were being
      adequately perfused.

PMID- 8308749
TI  - The effect of epidural anaesthesia with 1% lidocaine on the pressor response to
      dynamic exercise in man.
AB  - 1. In order to examine the sensitivity to local anaesthetics of afferent neural
      feedback from working muscle during dynamic exercise, sixteen subjects cycled for
      12 min before and after epidural anaesthesia using 1% lidocaine. The presence of
      afferent neural blockade was verified by elimination of the blood pressure
      response to a cold pressor test, laser-induced evoked potentials and increases in
      pain detection and tolerance thresholds of the foot. Conversely, epidural
      anaesthesia had no effect on these variables in the unblocked skin areas or on
      electrically evoked potentials in blocked or unblocked skin. 2. During dynamic
      exercise, heart rate increased as did mean arterial pressure and cardiac output.
      Mean arterial pressure remained at the exercise level during post-exercise
      ischaemia, but heart rate and cardiac output decreased while total peripheral
      resistance increased. Epidural anaesthesia did not significantly affect these
      variables during rest, dynamic exercise, post-exercise ischaemia or recovery. 3.
      The results of this study show that, in order to affect blood pressure during
      dynamic exercise, epidural anaesthesia must block the pressor response to post
      exercise ischaemia. The implication of these data is that complete or almost
      complete block of group III and/or group IV muscle afferents is necessary to
      inhibit the pressor response to dynamic exercise in man.

PMID- 8308750
TI  - Neural control of cardiovascular responses and of ventilation during dynamic
      exercise in man.
AB  - 1. Nine subjects performed dynamic knee extension by voluntary muscle
      contractions and by evoked contractions with and without epidural anaesthesia.
      Four exercise bouts of 10 min each were performed: three of one-legged knee
      extension (10, 20 and 30 W) and one of two-legged knee extension at 2 x 20 W.
      Epidural anaesthesia was induced with 0.5% bupivacaine or 2% lidocaine. Presence
      of neural blockade was verified by cutaneous sensory anaesthesia below T8-T10 and
      complete paralysis of both legs. 2. Compared to voluntary exercise, control
      electrically induced exercise resulted in normal or enhanced cardiovascular,
      metabolic and ventilatory responses. However, during epidural anaesthesia the
      increase in blood pressure with exercise was abolished. Furthermore, the
      increases in heart rate, cardiac output and leg blood flow were reduced. In
      contrast, plasma catecholamines, leg glucose uptake and leg lactate release,
      arterial carbon dioxide tension and pulmonary ventilation were not affected.
      Arterial and venous plasma potassium concentrations became elevated but leg
      potassium release was not increased. 3. The results conform to the idea that a
      reflex originating in contracting muscle is essential for the normal blood
      pressure response to dynamic exercise, and that other neural, humoral and
      haemodynamic mechanisms cannot govern this response. However, control mechanisms
      other than central command and the exercise pressor reflex can influence heart
      rate, cardiac output, muscle blood flow and ventilation during dynamic exercise
      in man.

PMID- 8308751
TI  - Rundown of N-methyl-D-aspartate channels during whole-cell recording in rat
      hippocampal neurons: role of Ca2+ and ATP.
AB  - 1. N-methyl-D-aspartate (NMDA) channel activity was studied on cultured rat
      hippocampal neurons in whole-cell voltage-clamp mode. NMDA responses were evoked
      by rapid application of NMDA and the cytosol was modified using pipette dialysis
      and intracellular perfusion. 2. In the presence of 2 mM [Ca2+]o with 2.4 mM BAPTA
      (1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) and 0.4 mM Ca2+ in the
      whole-cell pipette, the response evoked by regular applications of 10 microM NMDA
      gradually decreased during prolonged whole-cell recording. After 25 min the peak
      current was reduced to 56 +/- 1.6% of control. Channel 'rundown' could be
      prevented by inclusion of an ATP regenerating solution in the pipette. 3. Rundown
      did not occur in Ca(2+)-free medium even in the absence of added ATP regenerating
      solution. Rundown was also prevented by increasing [BAPTA]i to 10 mM whereas
      raising [Ca2+]i by inhibiting the Na(+)-Ca2+ exchanger or by perfusing the patch
      pipette with high [Ca2+]i (15-1000 microM) reversibly inhibited the NMDA current.
      By contrast, the rundown of kainate responses was Ca(2+)-independent. 4. The rate
      and reversibility of rundown was use-dependent. Rundown did not occur with
      infrequent NMDA applications (0.2/min). Following channel rundown in Ca(2+)
      containing medium, a 5 min pause in agonist applications or adding ATP
      regenerating solution by intracellular perfusion resulted in complete recovery.
      However, rundown did not recover following large currents evoked by 300 microM
      NMDA or when 10 mM EGTA was used as the intracellular buffer. Protease inhibitors
      did not prevent irreversible rundown. 5. ATP-gamma-S (4 mM) was less effective
      than the ATP regenerating solution in preventing rundown. Likewise, intracellular
      dialysis with alkaline phosphatase, phosphatase 1 or calcineurin did not induce
      rundown and addition of phosphatase inhibitors also did not block rundown. Thus
      receptor dephosphorylation did not appear to be primarily responsible for channel
      rundown. 6. The mean open time and unitary conductance of the NMDA channel were
      unaffected by rundown as estimated by fluctuation analysis. The conductance was
      42.8 +/- 2.9 nS before and 43.7 +/- 2.8 nS after rundown. The mean open times
      were 17.3 and 4.0 ms before and 15.9 and 4.0 ms after rundown. However the open
      probability was reduced following rundown as determined by the onset of MK-801
      block of steady-state NMDA currents. 7. Our results suggest that an increase in
      intracellular calcium leads to channel rundown during whole-cell recording by
      reducing the open probability of the NMDA channel.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8308753
TI  - Cytoplasmic Ca2+ oscillation in rat megakaryocytes evoked by a novel type of
      purinoceptor.
AB  - 1. The responses of megakaryocytes isolated from rat bone marrow to externally
      applied adenosine triphosphate (ATP) were investigated in the whole-cell mode by
      the use of nystatin perforated patch-clamp technique. 2. ATP at 1-100 microM
      evoked periodic outward currents at a holding potential of -40 mV. The reversal
      potential of the currents was close to K+ equilibrium potential (EK) and the K+
      channel blockers such as quinine and quinidine suppressed the currents,
      indicating that the outward currents are predominantly carried by K+. 3. Since it
      has been reported that adenosine diphosphate (ADP) evoked monophasic K+ current
      using a conventional whole-cell recording, we compared the results obtained by
      perforated and conventional patch-clamp techniques. The crucial difference
      between our results and previous results was due to the intracellular perfusion
      with internal solution containing a high concentration of EGTA by which both
      current shape and concentration response were modified. 4. The membrane permeable
      Ca2+ chelator, 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (acetoxy
      methyl ester; BAPTA AM), inhibited the K+ current concentration dependently,
      suggesting that ATP-induced oscillatory K+ currents are caused by changes in
      cytoplasmic free Ca2+ concentration ([Ca2+]i). 5. With increasing ATP
      concentration, the frequency and the maximum amplitude of K+ current oscillation
      increased and the latency of current, which is the period required to activate
      the first K+ current after ATP application, decreased. 6. ADP, 2-methylthio-ATP
      and ATP-gamma-S could also evoke the periodic K+ currents, but adenosine, uridine
      triphosphate (UTP) and alpha-beta-methylene adenosine 5'-triphosphate (AMP-CPP)
      failed. 2-Methylthio-ATP was the most potent agonist; next was ADP which showed a
      10-30 times stronger effect than ATP. Cross-desensitization was observed between
      ATP and ADP, but not between ATP or ADP and thrombin. 7. Extracellular Ca2+ was
      not required for the ATP-induced K+ current activation, indicating that Ca2+
      released from intracellular pools induced the oscillatory response. In addition,
      the agonist potency increased when extracellular Ca2+ concentration ([Ca2+]o)
      decreased, suggesting that the principal agonists might be ATP4- and ADP3-. 8.
      The results suggest the presence of a novel subtype of purinoceptor in the
      megakaryocyte plasma membrane which induces cytoplasmic Ca2+ oscillation and
      evokes periodic K+ current flux.

PMID- 8308752
TI  - Two phosphatase sites on the Ca2+ channel affecting different kinetic functions.
AB  - 1. Changes in dihydropyridine-sensitive (L-type) Ca2+ channel kinetics were
      studied after prolongation of intrinsic phosphorylated time by the phosphatase
      inhibitor okadaic acid (OA) in cell-attached patches made from single isolated
      rabbit ventricular myocytes, using barium as the charge carrier. 2. At low
      concentrations (0.001-1 microM), OA decreased the number of sweeps without
      openings, while open duration was not changed. However, when cells were
      pretreated by a membrane-permeant cyclic AMP, 0.1 microM OA induced long-lasting
      channel openings as well. 3. At high concentrations (10-750 microM), OA
      additionally induced long-lasting openings, resulting in open time distributions
      that were best fitted by two exponentials. 4. The durations of an available state
      (TS) and an unavailable state (TF) were estimated by the numbers of non-blank
      sweeps per run and blank sweeps per run by applying repetitive 45 ms steps at 2
      Hz to 0 mV from holding potentials of -80 mV. TS was well fitted by an
      exponential curve, of which the time constant was increased from 0.67 to 1.60
      sweeps by 0.1 microM OA, while TF was 0.347 sweeps and remained unchanged. 5. OA
      activated brief openings and long-lasting, wide openings in a concentration
      dependent manner. Namely, we find different dose-response relationships for the
      two kinetic effects of increased opening probability (mode 1) and prolongation of
      opening (mode 2). This behaviour suggests that there are at least two modulatory
      phosphorylation sites that are dephosphorylated by different phosphatases.

PMID- 8308756
TI  - False allegation. A concept in the context of rape.
AB  - "False allegation" is an imprecise term that is frequently used, but does not
      convey the same meaning to everyone. False allegations are statements that are
      unproven and untrue in the spirit of deliberateness or deceit. False allegations
      of sexual assault are relatively rare occurrences. For an allegation to be false,
      there first must be the motivation to deceive. There then must be unproven,
      untrue statements about the perpetrator(s), act(s), and/or setting that are
      either false accusations of false denials. It is recommended that false
      allegations be expressed using the following format: False allegation = false
      accusation/denial with respect to perpetrator(s)/act(s)/setting.

PMID- 8308754
TI  - Lateral hypothalamic lesions alter baroreceptor-evoked inhibition of rat
      supraoptic vasopressin neurones.
AB  - 1. Previous electrophysiological studies on rat hypothalamic supraoptic nucleus
      neurones have demonstrated that both the activation of peripheral baroreceptors
      (induced by a brief rise in arterial pressure consequent to an intravenous
      injection of an alpha-adrenergic agonist, metaraminol) and electrical stimulation
      in the diagonal band of Broca evokes a GABA-mediated postsynaptic inhibition
      which selectively involves the phasic-firing (putative vasopressin-secreting)
      neuronal population. Although baroreceptor-triggered inhibitions are abolished
      after diagonal band lesions, anatomical data support the hypothesis that the
      GABAergic neurones mediating both the baroreflex and electrically induced
      inhibitions are not located in the diagonal band, but rather in the lateral
      hypothalamus adjacent to the supraoptic nucleus. To determine the validity of
      this hypothesis, excitotoxic lesions were placed in the lateral hypothalamus and
      their effects on both baroreceptor- and diagonal band-evoked inhibitions were
      evaluated. 2. Male Long-Evans rats were initially anaesthetized with
      intraperitoneal pentobarbitone, stereotaxically injected with an excitotoxin
      (ibotenic acid) or vehicle into the lateral hypothalamus on the left side and
      allowed to recover. Three or more days later, animals were again anaesthetized
      with pentobarbitone and the ventral surface of their hypothalamus was exposed for
      electrophysiological recording of neurones in the left supraoptic nucleus. In all
      injected animals, extracellular recordings from antidromically identified,
      phasically firing supraoptic neurones were evaluated for their response to
      activation of peripheral baroreceptors and to electrical stimulation in the
      diagonal band. 3. Increases in arterial pressure sufficient to activate
      peripheral baroreceptors were achieved by intravenous bolus infusions of
      metaraminol (10 micrograms/10 microliters). In vehicle control animals (n = 6),
      the activity of 34/39 neurones was inhibited by baroreceptor activation. In
      lesion control animals (n = 13) similar inhibitions were observed from 60/65
      neurones. In the lateral hypothalamic lesioned group (n = 7), the activity of
      only 12/34 neurones were inhibited by similar elevations in blood pressure. 4.
      Ibotenic acid lesions in the lateral hypothalamus also disrupted the
      responsiveness of supraoptic neurones to electrical stimulation in the diagonal
      band. Whereas diagonal band stimulation in vehicle control and lesion control
      rats reduced the excitability in 7/9 cells and 15/19 cells respectively, only 1/7
      cells responded in the lesioned animals. 5. Lesions having a significant effect
      on the responsiveness of vasopressin-secreting neurones to baroreceptor
      activation extended laterally towards the nucleus of the lateral olfactory tract,
      dorsally into the striatum and medially to the fornix.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8308755
TI  - Respiratory sensations, cardiovascular control, kinaesthesia and transcranial
      stimulation during paralysis in humans.
AB  - 1. To determine whether discomfort associated with breathing (dyspnoea) is
      related to the chemical drive to breath, three subjects were totally paralysed
      while fully conscious. Subjective responses to a rising CO2 stimulus were
      obtained during rebreathing, rebreathing with CO2 added, and breath holding.
      Dyspnoea was measured with a 10-point Borg scale. 2. Following nasotracheal
      intubation and ventilation (oxygen saturation, O2,Sat, 98-100% and end-tidal CO2,
      PET,CO2, 30-40 mmHg), total neuromuscular blockade was induced by a rapid
      injection of atracurium (> 2.5 mg kg-1) and complete paralysis was maintained
      with an infusion (5 mg (kg h)-1). Paralysis was confirmed by abolition of the
      compound muscle action potentials of both the diaphragm and abductor hallucis
      evoked by supramaximal electrical stimulation of the relevant nerves.
      Communication via finger movement was preserved for the first 20-30 min following
      paralysis by inflation of a sphygmomanometer cuff on one arm. 3. Before and
      during complete paralysis, dyspnoea increased progressively during hypercapnia
      produced by rebreathing (with or without CO2 added to the circuit at 250 ml min
      1). The mean PET,CO2 eliciting 'severe' dyspnoea was 46 mmHg during rebreathing,
      42 mmHg during 'breath holding', and 52 mmHg during rebreathing with added CO2.
      There were no significant differences between the values obtained during
      paralysis and in the control study immediately before paralysis. The duration of
      breath holding was not prolonged by paralysis and the PET,CO2 at the 'break
      point' was not altered by paralysis. 4. Thus, dyspnoea is preserved following
      total neuromuscular blockade. This suggests that chemoreceptor activity, via the
      central neuronal activity which it evokes, can lead to discomfort in the absence
      of any contraction of respiratory muscles. 5. During paralysis, attempted
      contraction of arm, leg and trunk muscles increased heart rate and blood
      pressure. For attempted handgrip contractions, the increases in heart rate
      (range, 7-15 beats min-1) and mean arterial pressure (range, 20-32 mmHg) were
      similar to those recorded with actual contractions in trials immediately before
      paralysis. In one subject, graded increases in heart rate and blood pressure
      occurred for attempted contractions of 45 s duration over a range of intensities
      (0-100% maximal effort). 6. During complete paralysis, transcranial
      electromagnetic stimulation of the motor cortex produced illusory twitch-like
      movements of the wrist and digits. This also occurred in separate studies during
      complete ischaemic paralysis and anaesthesia of the forearm and hand.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8308757
TI  - Forensic responsibilities of the legal nurse consultant.
AB  - 1. Legal nurse consultants are registered nurses who use their clinical knowledge
      and expertise to assist attorneys with their cases in any context where law and
      medicine overlap. 2. A working knowledge of the four elements that constitute
      negligence is essential for a legal nurse consultant who works on medical and
      dental malpractice cases. 3. The ultimate goal of the legal nurse consultant is
      to provide the attorney with answers to questions relating to medical issues that
      may arise in a court of law. 4. The greatest challenge and opportunity the legal
      nurse consultant faces is the task of educating attorneys on the medical issues
      of their cases so that they are as knowledgeable and comfortable with these
      issues as they are with the liability issues.

PMID- 8308758
TI  - The role of the battered woman specialist.
AB  - 1. Nurses must recognize that every battered woman is a crime victim. Battered
      women also are frequently sexually assaulted and raped by their abusive
      boyfriends or husbands. All states have criminal sexual assault statutes;
      approximately 40 states have marital rape statutes. 2. Consistent within the
      clinical knowledge base for domestic violence survivors are the following
      concepts that the battered woman needs to hear from the nurse: her history of
      abuse is believed, she is not crazy, no one deserves to beaten, she is not alone,
      domestic violence is a crime, there is hope the cycle of violence can be broken,
      and there are specific places where she can go for help. 3. Few nurses have
      received any formal training in the principles of clinical forensics and clinical
      forensic nursing. Many nurses have had to go outside of nursing to learn forensic
      skills. However, as more nurses enter clinical forensic nursing roles, the
      necessity of formal education becomes increasingly important.

PMID- 8308759
TI  - Survey report on forensic nursing.
AB  - 1. There are at least 1,200 registered nurses working in psychiatric forensic
      facilities, 5% of whom are master's prepared. In 1991, approximately 1,900
      student nurses were affiliated with an institution providing evaluation and
      treatment for mentally ill offenders. 2. Based on the response to this survey,
      there is an eagerness to develop a professional network of forensic psychiatric
      nurses. The nature of this practice tends to be isolating, with heretofore
      infrequent opportunities to share common concerns and challenges. 3. Forensic
      psychiatric nurses represent a stable work force of substantial tenure. The most
      rewarding aspects of forensic nursing identified by the survey were the potential
      for autonomous professional practice and the unique challenges of providing care
      in a security environment.

PMID- 8308760
TI  - Forensic aspects of health care: new roles, new responsibilities.

PMID- 8308761
TI  - Forensic nursing. Diversity in education and practice.
AB  - Forensic nursing, as a professional discipline, originally defined its role as a
      medical examiner's investigator in the field of death investigation. However,
      with the evolution of a new area of clinical practice, the application of
      forensic science to nursing reveals a wider role in the investigation of crime
      and in the legal process. Forensic nursing, as a clinical subspecialty, fills a
      complementary role to clinical forensic medicine. As an emerging discipline,
      clinical forensic nursing recognizes that health care providers must assume a
      mutual responsibility with forensic scientists and the criminal justice system in
      concern for the survivor of violent crime and perpetrators of criminal acts. The
      registered nurse can be a great asset in the forensic sciences. Death has become
      a respectable field of inquiry, demanding answers to satisfy the public need and
      demand to determine the cause and manner of death. Nurses can bring empathy and
      compassion--as well as excellent observation, clinical, and communication skills-
      to death investigation.

PMID- 8308762
TI  - Smoking and the risk of rheumatoid arthritis.

PMID- 8308763
TI  - Prognosis in rheumatoid arthritis: applying new technologies to old questions.

PMID- 8308764
TI  - Disabling fibromyalgia: appearance versus reality.

PMID- 8308765
TI  - HLA-DR antigens, Gm allotypes and antiallotypes in early rheumatoid arthritis-
      their relation to disease progression.
AB  - OBJECTIVE: Evaluation of the prognostic value of immunogenetic markers in early
      rheumatoid arthritis (RA). METHODS: Ninety-nine patients with definite RA and
      disease duration 24 months or less were followed with standardized assessment.
      Disability was assessed by the HAQ index and radiographic changes in hands and
      feet by the Larsen method. The frequencies of HLA-DR genes were determined by
      serological typing, Gm allotype distribution by classical hemagglutination
      inhibition test, and occurrence of anti-Gm allotypes by use of anti-Rh coats. The
      immunogenetic findings were related to disease severity after 2 years' followup.
      RESULTS: Functional capacity was well preserved, disease activity was less, but
      radiographic changes in hands and feet had increased considerably at study
      finish. A group of 13 patients had developed rapidly progressive changes of hip
      and/or shoulder joints, all requiring arthroplasty. There was a significantly
      increased frequency of HLA-DR4. Twenty-seven of the 68 HLA-DR4 positive patients
      were putatively homozygous. HLA-DR4 was not related to disability or to severe
      small joint destruction. However, progressive large joint damage was
      significantly more prevalent in homozygous patients (p < 0.01). Gm allotype
      distribution was normal and not related to clinical findings. Anti-Gm antibodies
      were common and frequently specific for nonhost Gm allotype. Fifty-six patients
      carried anti-G1m(a), and occurrence of this antibody was significantly associated
      with radiographic progression of small joints (p = 0.01), presence of nodules (p
      < 0.01) and number of active joints (p = 0.001). CONCLUSION: Immunogenetic
      markers aided in identifying patients with early RA with more severe disease.

PMID- 8308766
TI  - Smoking and risk of rheumatoid arthritis.
AB  - OBJECTIVE: To investigate smoking for its association with the incidence of
      seropositive and seronegative rheumatoid arthritis (RA). METHODS: A cohort of
      adult Finns was examined by the Social Insurance Institution's Mobile Clinic in
      1966-72. The 24,445 women and 28,364 men who had neither arthritis nor a history
      of it at the start of the study were followed until the end of 1989 using record
      linkage with the Institution's population register to identify patients entitled
      to free antirheumatic medication. Sufficient information was obtained on 512
      incident cases of RA, of whom 119 men and 229 women were seropositive and 42 men
      and 122 women seronegative. RESULTS: There was a close association between
      smoking and the incidence of seropositive RA in men. It was not due to
      confounding by age, geographical location of residence, marital status, social
      class, self-perceived general health, or body mass index, although these factors
      correlated with smoking history. As adjusted for these factors, the relative risk
      of seropositive RA was 2.6 (95% confidence interval, 1.3-5.3) in male ex-smokers
      and 3.8 (95% confidence interval, 2.0-6.9) in current smokers, in comparison with
      the men who had never smoked. The association persisted throughout the entire
      followup period, but it was most distinct after the first 14 years of followup.
      Smoking did not predict seropositive RA in women, nor was it predictive of
      seronegative RA in men or women. CONCLUSION: Exposure to tobacco smoke, or some
      factor or cluster of factors associated with smoking, may trigger the production
      of rheumatoid factors and, in interaction with the male sex, subsequently
      contribute to the development of clinically manifest RA.

PMID- 8308767
TI  - The stress process in rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the Stress Process Model proposed by Pearlin and
      colleagues by examining the role of personal and social resources in mediating
      the relationship between the rheumatoid arthritis (RA) related stressors of
      functional disability, pain, and flares, and the outcome of depressive symptoms.
      METHODS: Data are from 285 patients who participated in a study of the natural
      history of RA, comorbidity and depression. Measures include the Center for
      Epidemiologic Studies-Depression (CES-D) scale, the Arthritis Impact Measurement
      Scale Functioning and Pain scales, the Lubben Social Network scale, and items
      indicating sociodemographic status, health status and personal resources. A
      series of hierarchical regression analyses with multiplicative interaction terms
      were conducted. RESULTS: Substantial consistency between the Stress Process Model
      and relationships observed in the data was demonstrated. CONCLUSION: Although no
      claim is made to having demonstrated that the observed relationships are causal,
      the fact that the data are consistent with the model invites a prospective
      analysis in which the ordering of the variables over time can be established
      unambiguously. Because of the implications of the Stress Process Model for the
      design of psychosocial interventions, such a test is especially important.

PMID- 8308768
TI  - A comparison of low dose methotrexate bioavailability: oral solution, oral
      tablet, subcutaneous and intramuscular dosing.
AB  - OBJECTIVE: To compare the relative bioavailability of low dose methotrexate (MTX)
      administered as tablet, oral solution, and subcutaneous (sc) injection to that of
      intramuscular (im) injection in patients with rheumatoid arthritis (RA). METHODS:
      Twelve patients meeting the American College of Rheumatology criteria for RA had
      serial blood MTX concentration samples drawn over a 24-h period after receiving
      their normal weekly MTX dose. Relative bioavailability (F) of the tablet and oral
      solution formulations was determined by comparison of the area under the time
      versus-serum-concentration curves (AUC) for the 2 different oral formulations as
      a percentage of the AUC for im injection. Also, relative bioavailability of the
      sc formulation was compared to im in 6 of the patients. RESULTS: Mean F for the
      oral tablet was 0.85, while that for the oral solution was 0.87. Both oral
      formulations showed a statistically significant difference in mean F when
      compared to im (tablet vs im, p = 0.002, oral solution vs im, p = 0.009). No
      statistically significant difference, however, was found in mean relative
      bioavailability between tablet and solution (p = 0.744). The mean F for sc was
      0.97; no statistically significant difference existed between the mean F values
      for the sc and im routes of administration (p = 0.657). CONCLUSIONS: Our data
      suggest the oral solution may be substituted for tablet dosing and sc injection
      substituted for im. Thus, a variety of different dosing methodologies may be
      considered providing the most appropriate route in each patient, given issues of
      compliance, medication cost, and preference.

PMID- 8308769
TI  - Adverse effects of low dose methotrexate therapy in rheumatoid arthritis.
AB  - OBJECTIVE: To determine (1) the risk of treatment termination for low dose,
      weekly methotrexate (MTX) therapy in patients with rheumatoid arthritis (RA), and
      (2) the prevalence, nature and predictors of adverse effects due to longterm low
      dose MTX therapy. METHODS: A 13-year, retrospective survey of all patients with
      RA receiving low dose MTX therapy was conducted using life table, logistic
      regression and case control methods of analyses. Major and minor adverse effects
      were defined. RESULTS: Consecutive patients with RA (144) starting MTX (mean dose
      8.2 mg/week) were observed to have a 75% risk of treatment termination at 60
      months. Reasons for 81 patients stopping MTX were adverse effects (43), loss/lack
      of effect (18), other medical and nonmedical reasons (13), and lost to followup
      (7). Sixty-two patients experienced 83 major adverse events, including
      gastrointestinal symptoms (29), hepatic enzyme test abnormalities (23),
      pneumonitis (5) and severe leukopenia (8). Aging was the only predictor of
      treatment discontinuation associated with a major toxicity. Five patients
      developed a malignancy during the observation period. CONCLUSIONS: In our survey
      the risk of treatment termination was 75% in patients with RA taking MTX after 60
      months. An adverse drug effect is a more common reason for treatment termination
      (53%), compared to loss/lack of beneficial effect (22%) or other reasons (16%) or
      lost to followup (9%). Increasing age is associated with an increased risk of
      treatment termination associated with a major toxicity.

PMID- 8308770
TI  - The effects of nonsteroidal antiinflammatory drug therapy in early rheumatoid
      arthritis on serum levels of soluble interleukin 2 receptor, CD4, and CD8.
AB  - OBJECTIVE: Cell surface molecules can be shed by activated T lymphocytes and
      measured in serum to assess in vivo T cell activation. To evaluate the
      relationship between these serum markers and disease activity in rheumatoid
      arthritis (RA), we determined levels of soluble interleukin 2 receptor (sIL-2R),
      CD4 (sCD4), and CD8 (sCD8) in sera from a well characterized group of 26 patients
      with active RA treated with a nonsteroidal antiinflammatory drug (NSAID) alone.
      METHODS: A retrospective, blinded determination of sIL-2R, sCD4, and sCD8 levels
      in serum samples from patients with early, active RA participating in 2 trials of
      NSAID therapy. Commercially available enzyme linked immunosorbent assays were
      employed. Data analysis included nonparametric techniques and correction for
      multiple comparisons. RESULTS: The patients with RA had significantly elevated
      levels of sIL-2R at baseline compared with age matched healthy controls. During
      NSAID therapy, mean sIL-2R levels among responders decreased to lower levels
      while nonresponder levels increased, although these trends did not reach
      statistical significance. Patients with RA did not differ from controls in
      baseline measures of serum sCD4 or sCD8 levels. Moreover, the serum sIL-2R, sCD4,
      and sCD8 levels among patients did not vary significantly from their baseline
      measures during NSAID therapy, irrespective of response. CONCLUSION: Our results
      suggest that elevated levels of serum sIL-2R in early RA likely reflect
      generalized immune system activation, not always associated with elevated serum
      sCD4 or sCD8 levels or varying with other measures of disease activity in RA.

PMID- 8308771
TI  - Prospective 5-year followup of recombinant interferon-gamma in rheumatoid
      arthritis.
AB  - OBJECTIVE: To define clinical and laboratory outcomes of longterm recombinant
      interferon-gamma (rIFN-gamma) treatment of patients with rheumatoid arthritis
      (RA). METHODS: Patients with RA (70) completing a 12-week multicenter double
      blind trial comparing rIFN-gamma with placebo were enrolled in a longterm
      prospective protocol evaluating rIFN-gamma in RA. RESULTS: The majority of
      patients sustained clinical improvement for one year. Eight (11%) patients with
      RA continued to receive rIFN-gamma after 5 years. One patient fulfilled remission
      criteria. rIFN-gamma was well tolerated with remarkably few suspected adverse
      drug reactions. Forty-seven (67%) patients discontinued rIFN-gamma because of
      lack of efficacy, 7 (10%) because of concurrent illnesses, 5 (7%) were not
      compliant to study protocol, 3 (4%) developed suspected adverse drug reactions
      for a total of 62 (89%) withdrawals over the 5 years of followup. Patients
      continuing rIFN-gamma treatment for 5 years had lower initial total leukocyte and
      neutrophil counts and higher hemoglobin and hematocrit levels than patients who
      discontinued rIFN-gamma during the 5-year followup. CONCLUSIONS: Longterm
      treatment of RA with rIFN-gamma was generally well tolerated. Although many
      patients maintained sustained clinical improvement for at least one year, the
      main reason for discontinuing the drug over 5 years was the lack of continued
      benefit.

PMID- 8308772
TI  - Concentration-effect relationship of hydroxychloroquine in rheumatoid arthritis-
      a cross sectional study.
AB  - OBJECTIVE: To determine the relationship between hydroxychloroquine concentration
      and effect in patients with rheumatoid arthritis (RA). METHODS: Using a cross
      sectional study design, drug concentration and effect were measured at one time.
      Forty-three patients with RA, receiving hydroxychloroquine therapy for at least 6
      months and not receiving glucocorticosteroids, gold or penicillamine therapy were
      enrolled. The main outcome measures were hydroxychloroquine concentration and
      disease activity measured as degree of synovitis, pain, duration and intensity of
      morning stiffness, impairment of activities of daily living, patients' and
      physicians' subjective assessment of disease, erythrocyte sedimentation rate, and
      rheumatoid factor (RF). Hemoglobin and albumin concentrations were also recorded.
      RESULTS: Patients with none or mild intensity of morning stiffness, those with
      stiffness lasting less than 0.5 h and those with negative RF had significantly
      higher hydroxychloroquine blood concentrations than those in whom these measures
      indicated a more active disease (Mann-Whitney U test, p < 0.05). Similar trends
      were recorded for 3 other disease activity measures (p = 0.12-0.24). Analysis of
      all 9 individual disease activity measures indicated that the groups with less
      active disease had higher mean blood concentrations of hydroxychloroquine than
      those with measures indicating more active disease (p < 0.01). CONCLUSION: Our
      data provide the first evidence of a concentration-response relationship for
      hydroxychloroquine in RA for individual disease activity measures. However, an
      unweighted summed score of disease activity did not correlate significantly with
      drug blood concentrations. A prospective study is necessary to confirm the
      relationship and to determine a therapeutic concentration range.

PMID- 8308774
TI  - Skin thickness score in systemic sclerosis: an assessment of interobserver
      variability in 3 independent studies.
AB  - OBJECTIVE: Using data from 3 independent studies, to quantify the interobserver
      reliability of semi-quantitative skin scoring methods (the original and the
      modified Rodnan skin thickness scores) used to assess the degree and extent of
      cutaneous thickening in systemic sclerosis (SSc). METHOD: Interobserver
      variability of the original Rodnan skin thickness score method (cutaneous
      thickness assessed in 26 body surface areas using a 0-4 scale) was evaluated in
      one study. The modified Rodnan method (cutaneous thickness assessed in 17 body
      surface areas using a 0-3 scale) was evaluated in 2 studies. In all 3 studies,
      each patient's skin thickness was assessed by 6 or 7 observers in a blinded
      fashion. RESULTS: The overall within patient standard deviations were not
      statistically different in all 3 studies (5.4, 4.6 and 4.6) irrespective of the
      overall mean skin thickness scores (26.6, 18.3 and 17.7). With the original
      Rodnan technique, the within patient standard deviation tended to be higher in
      patients with higher skin thickness scores. In the 2 studies which used the
      modified technique, no significant differences in within patient standard
      deviation were noted between high and low skin thickness scores. CONCLUSIONS:
      Three independent studies demonstrate that the Rodnan skin thickness scoring
      techniques are reproducible among different observers (the within patient
      standard deviation being consistently about 5 units). Our data provide valuable
      information needed for sample size calculations for SSc trials in which skin
      thickness score is an outcome variable.

PMID- 8308773
TI  - Rheumatic manifestations in human immunodeficiency virus positive and negative
      individuals: a study of 2 populations with similar risk factors.
AB  - OBJECTIVE: Assess the impact of human immunodeficiency virus (HIV) infection on
      the onset of rheumatic manifestations in HIV+ patients, and to compare them with
      a control HIV- group with similar risk factors. METHODS: We prospectively studied
      74 consecutive HIV+ patients, looking for clinical and laboratory findings of
      rheumatic manifestations and compared them with 72 control subjects with similar
      risk factors for HIV who tested negative for HIV. RESULTS: Rheumatic
      manifestations were more frequently observed in the HIV+ group than the HIV-group
      (p < 0.001): Arthralgias were found in 34 (45%), arthritis in 8 (10%), and
      Reiter's syndrome in 6 (8%). Laboratory findings revealed rheumatoid factor in 16
      (21%) HIV+ vs 2 (2%) in HIV-, antinuclear antibodies in 13 (17%) HIV+ vs 0 in HIV
      , IgG anticardiolipin antibodies in 70 (94%) HIV+ vs 7 (9%) in HIV- (p < 0.001).
      Hyperuricemia was found in 31 HIV+ patients (41%), and hypouricemia in 4 (5%),
      compared with none in the HIV- group (p < 0.0001). Neoplasia were identified in
      13 HIV+ patients, in 7 associated with hyperuricemia and 3 with hypouricemia. Of
      interest, 2 patients had urate abnormalities before the diagnosis of neoplasia.
      CONCLUSIONS: Our study suggests that rheumatic manifestations are more prevalent
      in HIV+ patients. In advanced HIV infection, hypo and hyperuricemia may be
      considered markers of neoplasia.

PMID- 8308775
TI  - Dermatomyositis and ovarian cancer: a report of 7 cases and literature review.
AB  - The relationship between malignancy and inflammatory myopathies is now
      statistically well established. However, the link between polymyositis (PM) or
      dermatomyositis (DM) and ovarian cancer (OC) has never been clearly emphasized.
      OC is the 6th most frequent malignancy, occurring in about 1% of the general
      female population. We describe 7 cases of DM associated with OC (proven in 6
      patients, and very probable in a 7th), in a series of 140 adult inflammatory
      myopathies followed in our institution [84 PM and 56 DM (including 45 female)].
      Twenty-four patients had associated malignancy (12 PM and 12 DM). Without
      considering the probable case, OC occurred in 13.3% (6/45) of the total female DM
      population, a much higher rate than the 1% observed in the general female
      population; and in 21.4% (6/28) of females aged over 40 with DM. In women over 40
      with DM, ovarian cancer has a major position among associated internal
      malignancies, and has to be adequately looked for by physicians.

PMID- 8308776
TI  - Sex ratio in the spondyloarthropathies and its relationship to phenotypic
      expression, mode of inheritance and age at onset.
AB  - OBJECTIVE: To investigate the interrelated effect of phenotypic expression [i.e.,
      primary ankylosing spondylitis (1 degree AS) or disease secondary to psoriasis
      (Ps) AS or inflammatory bowel disease (IBD)AS], age at onset, sex and inheritance
      of responsible genes in AS. METHODS: Three studies were performed to evaluate
      1949 subjects with AS. Subgroups of the patients were formed for each study
      depending on disease type (1 degree AS = 1695; Ps AS = 173; IBD AS = 81), nature
      of inheritance or age at onset of AS symptoms. These groups were further
      subdivided to assess the effect of sex. RESULTS: The sex ratio of the entire
      group was 2.6:1 in favor of men. However, IBD AS had an equal sex distribution as
      does IBD alone. By contrast, Ps, which has an equal sex ratio as a lone event or
      in association with arthritis, resulted in a male dominance of 4.1:1 when it
      occurred as Ps AS. Women with IBD AS had a significantly younger onset compared
      to women with 1 degree AS [mean onset 21.7 years (SD 6.65) vs mean onset 24.4
      years (SD 9.79), respectively; p = 0.019]. A younger age at onset was found in
      women with familial disease [mean 22.2 years (SD 7.55)] compared with the mean
      onset of sporadic disease in women [24.5 years (SD 10.0); p = 0.0059]. There was
      a progressive fall in the sex ratio as the age at onset increased (p = 0.053).
      For example: M:F ratio of < 20 years old was 3:1 compared to 1.8:1 for those with
      an onset of > 40 years. CONCLUSION: Sex ratio and age at onset are influenced
      both by each other and such factors as disease type and familial versus sporadic
      occurrence. These data help provide a predictable pattern of disease in
      spondyloarthropathy.

PMID- 8308777
TI  - Chest radiographs as a screening test for diffuse idiopathic skeletal
      hyperostosis.
AB  - OBJECTIVE: To evaluate the sensitivity, specificity, predictive value, interrater
      reliability and intrarater reliability of using chest radiographs as a screening
      tool for the diagnosis of diffuse idiopathic skeletal hyperostosis (DISH).
      METHODS: After review of thoracic spine radiographs by 2 "gold standard"
      physicians, 45 patients with DISH meeting the criteria of Resnick and Niwayama
      were contrasted with 106 control patients consisting of 45 with thoracic
      spondylosis, 45 who lacked spondylosis and whose thoracic spine radiographs were
      otherwise normal for the age of the patient, and 16 with ankylosing spondylitis.
      The chest radiographs on the 151 subjects were placed in random order and read
      independently using an ordinal diagnostic certainty scale by 2 "test"
      radiologists, experienced in reading bone radiographs. Two months later the order
      of chest radiographs was rerandomized and the films reassessed by the same test
      radiologists. RESULTS: The averages for the diagnostic and population test
      characteristics were sensitivity = 77%; specificity = 97%; positive predictive
      value = 91%; and, negative predictive value = 91%. The area under the receiver
      operating characteristic curves was 0.975 and 0.976 for the radiologists, and
      kappa was 0.93, demonstrating that interrater reliability was high. On rereading
      the chest radiographs, intrarater reliability was exceptional (weighted kappa of
      0.90 and 0.96 for the two test radiologists). DISH patients whose chest
      radiographs were read as not demonstrating DISH had significantly less extensive
      disease. CONCLUSIONS: We conclude that chest radiographs are a reliable and valid
      screening tool for the diagnosis of DISH.

PMID- 8308778
TI  - Reliability of new indices of radiographic osteoarthritis of the hand and hip and
      lumbar disc degeneration.
AB  - OBJECTIVE: To develop a method for assessing the presence and severity of
      radiographic features of osteoarthritis (OA) of the hip and hand, and thoracic
      and lumbar disc degeneration. METHODS: An atlas illustrating scoring of
      individual radiographic features and summary grades for individual joints was
      developed. Three readers evaluated 31 pelvic films, 27 hand films, and 25 lateral
      lumbar and thoracic spine films selected from a community based sample of healthy
      elderly women. Interrater agreement between the 3 readers, and test-retest
      agreement for one of the readers, were estimated by the intraclass correlation
      coefficient (ICC) and kappa statistic. RESULTS: Interrater agreement (ICC, unless
      otherwise noted) for individual radiographic features of the hip ranged from 0.66
      for osteophytes to 0.80 for narrowing. For the 9 interphalangeal (IP) joints of
      the hand, agreement ranged from 0.42 (kappa) for sclerosis to 0.93 for narrowing,
      and for the lumbar spine from 0.55 (kappa) for sclerosis to 0.95 for narrowing.
      Interrater agreement for summary grades of radiographic findings was as follows:
      hip, 0.81; 5 distal interphalangeal joints (DIP), 0.89; 4 proximal
      interphalangeal joints (PIP), 0.82; and lumbar spine, 0.93. Intrarater agreement
      for summary grades was as follows: hips, 0.79; 5 DIP, 0.86; 4 PIP, 0.81; and
      lumbar spine, 0.90. CONCLUSION: We have developed reliable indices of the
      presence and severity of radiographic features of hip and hand OA and spinal disc
      degeneration for use in epidemiologic studies. The assessment includes grading of
      individual radiographic features, which allows for the independent variation in
      these features often found in OA and a summary grade of disease that is derived
      from the presence and severity of individual features.

PMID- 8308779
TI  - Reliability and validity of the measurement of position sense in women with
      osteoarthritis of the knee.
AB  - OBJECTIVE: We examined the test-retest reliability and the construct validity of
      the measurement of knee position sense for describing the functional
      weightbearing performance of women with osteoarthritis (OA) of the knee. METHODS:
      For the purpose of this study, position sense was defined as the error occurring
      when subjects attempted to reproduce a criterion angle in standing with visual
      cues eliminated. Five such tests were recorded photographically on 3 different
      occasions. On each occasion the 10 subjects also completed a self-paced walking
      test over a 13 m indoor walkway. RESULTS: The photographic measurements were
      reproducible (r = 0.90) and there was no change in positioning accuracy across
      sessions. There was a significant (p < 0.05) inverse correlation of 0.70 between
      the standard deviation of the mean individual measurements of position sense
      (precision of the test) and those of walking speed. CONCLUSION: Our study
      demonstrates good measurement reliability and a comparable mean angular error
      with repeated tests. It also suggests the amplitude of the variability of this
      error is a strong determinant of an individual OA patient's functional
      performance in walking.

PMID- 8308780
TI  - Weather conditions and complaints in fibromyalgia.
AB  - Patients with musculoskeletal disorders, including fibromyalgia syndrome (FS),
      often state that weather conditions modulate their complaints. There have been a
      few studies concerning this issue, but the results appear to be contradictory. We
      tried to relate the subjective symptoms of pain, stiffness, sleep and mood in
      patients with FS to objective meteorological factors. Correlation analyses showed
      no relation between the subjective complaints and the meteorological factors. The
      symptoms pain, stiffness and fatigue, however, showed a strong intercorrelation.

PMID- 8308781
TI  - Litigation, sleep, symptoms and disabilities in postaccident pain (fibromyalgia)
AB  - Twenty-four patients with chronic postaccident pain were studied with self-rating
      symptom checklists, polysomnography and disability questionnaires. All except one
      had fibromyalgia. Eight had litigation resolved (R) while 16 had medicolegal
      claims still unresolved (UR). Patients from the R group were older, with a longer
      duration of symptoms and more occupation handicap compared to those from the UR
      group. There were no significant differences between the 2 groups in other
      demographic data, nature of accident, symptoms, polysomnographic findings and
      disability. Medicolegal claim status in these patients did not differentiate the
      outcome of their symptoms. Implications for litigation, treatment and further
      studies are discussed.

PMID- 8308783
TI  - Association of methotrexate treatment with a decrease of double negative (CD4-CD8
      ) and gamma/delta T cell levels in patients with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: It has been suggested that double negative (CD4-CD8-) (DN) and
      gamma/delta T cells may be involved in some autoimmune diseases. We investigated
      peripheral blood DN and gamma/delta T cell levels in patients with active
      juvenile rheumatoid arthritis (JRA). METHODS: DN and gamma/delta T cell levels
      were measured in 42 patients with active JRA and in 10 healthy controls
      comparable for age by an immunofluorescence double staining procedure. RESULTS:
      All 3 JRA onset types had DN and gamma/delta T cell levels not significantly
      different from those of controls, although a wide scattering of data was present.
      No correlation was found between DN or gamma/delta T cell levels and erythrocyte
      sedimentation rate values or the number of active joints. When patients were
      divided according to treatment, we found that DN and gamma/delta T cell levels
      were significantly lower (p = 0.001, p = 0.02, respectively) in patients
      receiving methotrexate (MTX) than in patients not receiving MTX. The association
      of MTX treatment with a decrease in DN and gamma/delta T cell levels was also
      confirmed in a followup study of individual patients. Among patients not
      receiving MTX, patients with systemic JRA presented DN T cell levels
      significantly higher than those of controls. In 5 patients with pauciarticular
      JRA DN and gamma/delta T cell levels were higher in synovial fluid than in the
      peripheral blood. CONCLUSIONS: We found an increase in peripheral blood DN T cell
      levels in systemic JRA; treatment with MTX appears to be associated with a
      decrease in DN and gamma/delta T cell levels.

PMID- 8308782
TI  - Established fibromyalgia syndrome and parvovirus B19 infection.
AB  - OBJECTIVE: To determine the seroprevalence of prior and persistent parvovirus B19
      (B19) infection in a group of patients with fibromyalgia (FS) compared with
      controls. METHODS: Fifteen female patients with FS who recalled a viral prodrome
      (+VP) preceding the onset of FS symptoms and eleven patients with FS who did not
      recall any such illness (-VP) were selected from a referral practice. We excluded
      patients with FS who described a history of trauma prior to the onset of FS
      symptoms. Twenty-six female medical workers served as controls. Serum IgM and IgG
      anti-B19 antibodies were measured by ELISA: Polymerase chain reaction (PCR)
      products from serum were analyzed by dot blot hybridization for B19 DNA. Fisher's
      2-tailed exact test was used to compare the proportion of positive serologies in
      each group. RESULTS: No patient or control had positive IgM levels. For all
      patients with FS, the prevalence of prior B19 infection was comparable to that of
      healthy controls (11/26 vs 12/26, p = 1.00) and that of the general population.
      No significant difference was found in the prevalence of prior B19 infection in
      FS + VP and FS-VP patients (8/15 vs 3/11, p = 0.25). None of the patients or
      controls showed evidence for persistent B19 viremia, as determined by PCR
      analysis. CONCLUSION: Our data do not suggest that B19 plays a pathogenic role in
      this population of patients with FS. Testing for IgM against B19 within 2-3
      months of symptom onset may prove more helpful in further defining the role of
      B19 in FS.

PMID- 8308784
TI  - Interleukin 6 and autoantibodies in juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To assess whether interleukin 6 (IL-6) may influence autoantibody
      production, the correlation of rheumatoid factors (RF) and antitype II collagen
      antibodies with IL-6 was determined in children with juvenile rheumatoid
      arthritis (JRA). METHODS: IL-6 was measured by proliferation of the B-9 cell line
      or by ELISA: IgG, IgA, and IgM RF were measured by ELISA: RESULTS: Plasma IL-6
      levels were higher in patients with polyarticular JRA than controls. In serial
      studies, the presence of a greater number of RF isotypes and IgG antinative type
      II collagen antibodies correlated with higher IL-6 levels [1650 x divided by 3.4
      vs 831 x divided by 4.4, p < 0.01 (geometric mean x divided by SD); and 1828 x
      divided by 5.9 vs 646 x divided by 4.1, p < 0.005, respectively]. The change in
      RF isotype expression most often involved IgG or IgA RF. In vitro IgG RF
      production increased in one and became detectable in another 2 cases upon the
      addition of IL-6 to B cell cultures. CONCLUSION: Our results suggest that IL-6
      may promote the production of IgG and IgA RF and IgG antinative type II collagen
      antibodies.

PMID- 8308785
TI  - Chest expansion in healthy adolescents and patients with the seronegative
      enthesopathy and arthropathy syndrome or juvenile ankylosing spondylitis.
AB  - OBJECTIVE: To determine chest expansion measurements in healthy children and
      those with juvenile spondyloarthropathies. METHODS: Chest expansion, as defined
      by the difference between maximal inspiration and maximal expiration was measured
      in 157 healthy adolescents (112 boys and 45 girls) aged 11 to 15 years, 20
      patients with the seronegative enthesopathy and arthropathy (SEA) syndrome and 15
      with juvenile ankylosing spondylitis (AS). RESULTS: The median and mean chest
      expansion (+/- 2 SD) were 5.0 cm and 5.6 cm (+/- 3.52) for the whole group of
      healthy adolescents, 6.0 cm and 5.9 cm (+/- 3.64) for boys and 5.0 cm and 4.8 cm
      (+/- 2.69) for girls. The frequency distribution of the values was leptokurtic
      and skewed to the right and did not follow the normal pattern; nearly 90% of the
      measurements fell within the interval from 3 to 9 cm. Of all variables analyzed
      (age, height, weight, sex and health/disease status), only height correlated with
      chest expansion (r = 0.20, p = 0.01). Even so, the effect of all these variables
      explained only 13% of the total variance of the measurements. Interobserver and
      intraobserver intraclass correlation coefficients were moderate (0.58 and 0.67,
      respectively). Mean values and cumulative frequency distribution in asymptomatic
      and symptomatic SEA syndrome and patients with juvenile AS were similar to those
      from healthy adolescents. CONCLUSION: Measuring chest expansion does not seem to
      be a useful method for the rare cases of early involvement of the chest joints in
      SEA syndrome and juvenile AS.

PMID- 8308786
TI  - A case of systemic sclerosis with anticentromere, antitopoisomerase I, and anti
      U1RNP antibodies.
AB  - We describe a case of systemic sclerosis (SSc) positive for 3 autoantibodies;
      anticentromere antibody, antitopoisomerase I antibody, and anti-U1RNP antibody,
      It is known that coexistence of 2 of these 3 antibodies is rare and the
      coexistence of these 3 antibodies in serum from a patient with SSc has not been
      reported. In addition, we examined our stock serum samples from 236 cases with
      SSc or related disorders for the presence of specific antinuclear antibodies and
      were unable to find a serum sample containing all 3 antibodies.

PMID- 8308787
TI  - Henoch-Schonlein purpura associated with anti-Ro (SSA) and antiphospholipid
      antibody syndrome.
AB  - We describe a case of Henoch-Schonlein purpura with a history of recurrent deep
      vein thromboses found to have anti-Ro (SSA) and anticardiolipin antibodies.
      Association of these serologic markers with cutaneous vasculitis is discussed.

PMID- 8308788
TI  - Femoral fracture mimicking acute arthritis in Down's syndrome.
AB  - We describe a 38-year-old white woman with Down's syndrome with a history of
      chronic arthritis and hyperuricemia who presented with acute left knee pain,
      patellar tenderness and patello-femoral instability. Findings appeared due to a
      fracture of the lateral femoral condyle, which responded to conservative therapy
      with a spica cast. Patellofemoral instability in Down's syndrome can be
      associated with significant morbidity including femoral condyle fracture.
      Patients with Down's syndrome who present with acute knee arthritis responding
      poorly to antiinflammatory agents and other conventional therapy should be
      assessed for fractures related to patellar dislocation, as treatments for the 2
      disorders differ.

PMID- 8308789
TI  - Digital vasculitis following allergic desensitization treatment.
AB  - Systemic necrotizing vasculitis or a polyarteritis nodosa-like clinical
      presentation, is an unusual complication of immunotherapy (hyposensitization
      therapy). We describe a patient who developed features of vasculitis several
      years after beginning hyposensitization treatment for allergic rhinitis. In the 7
      months preceding the onset of the vasculitis he experienced 4 episodes of
      anaphylaxis immediately after receiving desensitization injections. The
      vasculitis was characterized by the abrupt onset of pain and discoloration of the
      middle 3 digits of his right hand. Cyanosis and small areas of frank necrosis of
      these digits were present. Erythrocyte sedimentation rate and C-reactive protein
      were elevated and total serum complement was decreased. The development of
      digital vasculitis following hyposensitization is clearly illustrated in this
      patient.

PMID- 8308790
TI  - Position dependent livedo reticularis in cholesterol emboli syndrome.
AB  - We describe a case of a 64-year-old Filipino man who presented with cholesterol
      emboli syndrome manifesting as worsening hypertension, renal failure and livedo
      reticularis involving the upper legs and lower abdomen. The livedo reticularis
      became very prominent with the patient standing, but completely vanished after
      several minutes of lying supine. Deep cutaneous biopsy of an area of skin that
      was found to be consistently involved with livedo reticularis demonstrated
      cholesterol clefts in several vessels, thus establishing the diagnosis in this
      patient, and avoiding the more problematic option of biopsying an involved
      visceral organ.

PMID- 8308791
TI  - Acute apatite podagra with negative birefringent spherulites in the synovial
      fluid.
AB  - We describe a young male patient who presented with acute podagra after jogging
      activity. He had no underlying pathology. Polarized light microscopy of the
      synovial fluid from his first metatarsophalangeal joint revealed numerous
      negative birefringent spherulites about 6 microns in diameter, presenting the
      typical appearance of Maltese crosses. The molar calcium/phosphorus ratio of
      these spherulites as determined by X-ray energy dispersive analysis was virtually
      identical to that of synthetic or pathologic apatite.

PMID- 8308792
TI  - Fusobacterium septic arthritis of the sternoclavicular joint.
AB  - We describe a case of septic arthritis of the sternoclavicular joint caused by
      Fusobacterium in an otherwise healthy young man. The Fusobacterium had
      morphologic features most in keeping with Fusobacterium (F.) necrophorum, which
      was a common organism in sternoclavicular septic arthritis in the preantibiotic
      era. To our knowledge this is the first reported case of a fusobacterium
      sternoclavicular joint infection in the antibiotic era. This case should lead to
      heightened awareness of sternoclavicular joint infection and fusobacterium joint
      infection in the healthy host.

PMID- 8308793
TI  - Endocarditis with left atrial thrombus formation in Behcet's disease mimicking
      myxoma.
AB  - A 51-year-old male patient with Behcet's disease had a large echogenic mass in
      the left atrium mimicking myxoma, documented by echocardiography. Postoperative
      pathological examination revealed left atrial thrombus, deep ulcerations of
      mitral valve leaflets with signs of active endocarditis. Cardiac evaluation with
      echocardiography should be considered in patients with Behcet's disease.

PMID- 8308794
TI  - Platelet 3H-imipramine uptake receptor density and serum serotonin levels in
      patients with fibromyalgia/fibrositis syndrome.

PMID- 8308795
TI  - Pleurodesis for refractory pleural effusion in systemic lupus erythematosus.

PMID- 8308796
TI  - Tetracyclines in arthritis.

PMID- 8308797
TI  - Vascular involvement in Behcet's disease.

PMID- 8308798
TI  - Hypothyroidism and chondrocalcinosis: new evidence for lack of association
      between the 2 pathologies.

PMID- 8308799
TI  - Pustulotic arthroosteitis triggered by echovirus 9?

PMID- 8308800
TI  - Scleroderma after exposure to domestic detergent LOC.

PMID- 8308801
TI  - Health promotion is not a Cinderella subject.

PMID- 8308802
TI  - Vestibular schwannoma.

PMID- 8308803
TI  - The genius of disease. 2. La Nausee--Jean-Paul Sartre.

PMID- 8308804
TI  - Rudolf Virchow--father of cellular pathology.

PMID- 8308805
TI  - Reflex sympathetic dystrophy and repetitive strain injury: temperature and
      microcirculatory changes following mild cold stress.
AB  - Temperature and blood flow studies were performed in the upper limbs of six
      patients with reflex sympathetic dystrophy (RSD), nine patients with repetitive
      strain injury (RSI) and 12 control subjects using thermography, laser Doppler
      flowmetry, infrared photoplethysmography and venous occlusion strain gauge
      plethysmography. The contralateral responses of the symptomatic and asymptomatic
      limbs were examined after being subjected, separately, to mild cold stress (20
      degrees C for 1 min). Altered thermoregulation and haemodynamics were evident in
      RSD. Though the pattern of response to contralateral cold challenge is similar to
      normal in RSI, vasodilatation and reduced vasomotion appears to be characteristic
      in this condition. Such changes may assist in distinguishing between RSD and RSI
      from other causes of chronic upper limb pain.

PMID- 8308806
TI  - Health promotion at work.
AB  - This study examined health promotion intervention amongst council employees and
      determined the extent that any changes were subsequently maintained. The results
      showed that even with modest intervention, beneficial changes were observed in
      alcohol consumption, diastolic blood pressure, body mass, waist/hips ratio, body
      fat, aerobic capacity and arm strength. Behavioural measures tended not to
      change, but this could be a consequence of unfocused questioning or insufficient
      intensity of the health promotion activities. The sickness and absenteeism rates
      improved during the intervention and maintenance phases, making a strong case for
      health promotion from the employer's perspective. A critique of the experimental
      procedure suggested that the testing venue, the methods of obtaining consent, the
      continuity of subjects, initial attitudes, the intensity of the intervention and
      the project delivery were all features that would contribute to a successful
      outcome.

PMID- 8308807
TI  - The impact of the National Breast Screening Programme on the incidence of breast
      cancer in a UK health district.

PMID- 8308808
TI  - The influence of diagnostic and therapeutic laparoscopy on patients presenting
      with an acute abdomen.
AB  - The role of laparoscopy in the management of patients presenting to one surgical
      firm with an acute abdomen is discussed. Sixty-seven laparoscopies have been
      performed over an 18 month period and it has altered the diagnosis in 19.4% of
      cases and the management in 13.4% of cases. At laparoscopy the diagnosis of
      appendicitis was made in 37 patients (81% had attempted laparoscopic
      appendicectomies); pelvic inflammatory disease in 15 patients; torted fimbrial
      cyst in two patients; and free pus in the right lower peritoneum as a result of a
      perforated appendix was seen in two patients. Normal laparoscopy was performed in
      five patients and four patients who presented with a perforated duodenal ulcer
      had the diagnosis confirmed at laparoscopy, in three cases the perforation was
      oversewn laparoscopically. Two laparoscopies were performed on trauma patients;
      one stabbing and one blunt trauma to the right hypochondrium. It has been
      demonstrated that diagnostic laparoscopy is a useful adjunct to the general
      surgeon's armamentarium. It is suggested that the skill of laparoscopy is passed
      on to junior trainee surgeons who can use this technique to help attain a
      diagnosis in patients presenting with an acute abdomen.

PMID- 8308809
TI  - The management of dental problems presenting to an accident and emergency
      department.
AB  - Patients with dental diagnoses, not necessarily traumatic, often present to
      accident and emergency departments and general medical practitioners. Few doctors
      have received much, if any, education in the management of these patients. A 6
      month prospective study revealed 107 patients (0.3% of new attenders) attending
      the accident and emergency department of Glasgow Royal Infirmary. Only 19 of
      these had suffered trauma. Medical staff in the department were only rarely able
      to make any diagnosis, and management of these patients took place on an
      empirical, symptomatic basis. Management could be improved by better education of
      medical students and doctors. Use of an algorithm may be appropriate.

PMID- 8308810
TI  - The population Doomsday forecast: lessons from Kerala.

PMID- 8308812
TI  - The Crowner's quest.

PMID- 8308813
TI  - Logic and magic in mainstream and fringe medicine.

PMID- 8308811
TI  - Control of neonatal group B streptococcal infection.
AB  - Group B beta-haemolytic streptococcus (GBS) is the leading cause of life
      threatening perinatal infection in developed countries. As immunization of women
      is not yet available, selective intrapartum chemoprophylaxis appears to be the
      best current strategy for preventing disease. All pregnant women should be
      screened for GBS at 26 to 28 weeks gestation. During labour, all colonized women
      with risk factors for invasive GBS neonatal infection should be treated with
      intravenous penicillin or ampicillin. Risk factors include preterm labour,
      premature rupture of membranes, intrapartum fever, multiple births, prolonged
      rupture of membranes, maternal diabetes, previous sibling with invasive GBS
      disease, and maternal GBS bacteriuria. The latter two categories warrant
      chemoprophylaxis regardless of maternal colonization status.

PMID- 8308814
TI  - The portrayal of the physician in non-medical literature--favourable portrayals.

PMID- 8308815
TI  - Successful therapy of the follicular occlusion triad in a young woman with high
      dose oral antiandrogens and minocycline.

PMID- 8308816
TI  - An unusual blue baby.

PMID- 8308817
TI  - Reconstruction of the anterior lower third of the face using a composite
      pectoralis major free flap.

PMID- 8308818
TI  - Successful resuscitation from hypothermic induced cardiac arrest using
      cardiopulmonary bypass.

PMID- 8308819
TI  - Breast cancer and pregnancy.

PMID- 8308820
TI  - How many physicians? An enigmatic dilemma.

PMID- 8308821
TI  - Drug misusers in police custody: a prospective survey.
AB  - Approximately 11% of individuals seen by forensic medical examiners in police
      custody in London are drug misusers. This prospective survey using an anonymized
      structured questionnaire attempted to define some of the characteristics of this
      selected group of drug misusers. The study was undertaken in Metropolitan Police
      Service stations (London, UK) within the area covered by Group IV Forensic
      Medical Examiners. One hundred and fifty consecutive drug misusers in police
      custody were assessed. Of these individuals 77% used heroin; 30% used both heroin
      and cocaine regularly; 72% were injecting drugs; 32% were being prescribed drugs
      (e.g. methadone) by general practitioners or drug agencies. Those individuals
      prescribed drugs spent a similar amount per day on illicit drugs as those who
      were not (100.30 pounds versus 106 pounds). Four per cent of individuals were HIV
      positive; 25.7% were hepatitis-B positive. Only 9.7% were aware that prophylaxis
      for hepatitis-B was possible. Seventy-four per cent had served previous prison
      sentences and of those 82% had used class A controlled drugs whilst serving the
      sentence. It is concluded that drug misusers seen in police custody tend to be
      recidivists. It seems that some clear means of identifying and ensuring referral
      and attendance at an appropriate agency may be the only way to break the cycle of
      drug misuse, prison and further drug misuse in this highly (self) selected group
      of patients.

PMID- 8308822
TI  - Large bowel biopsies in colitis: a clinicopathological collaboration.

PMID- 8308823
TI  - Sport-related sudden natural death in the City of Birmingham.
AB  - We undertook a prospective study of all consecutive deaths reported to the
      Coroner for Birmingham and Solihull in a 5 year period. We identified 52 sudden
      deaths associated with symptoms commencing during sport participation. We studied
      the characteristics of these individuals. The majority had been performing at
      accustomed levels of activity without symptoms for several years. The
      extrapolation of our findings to preventive strategies remains unclear but we
      wish to highlight the importance of recognizing premonitory effort-related
      symptoms.

PMID- 8308824
TI  - The genius of disease. 3. A journey round my skull--Frigyes Karinthy.

PMID- 8308825
TI  - Length of life in the ancient world: a controlled study.
AB  - The length of life for a population of ancient Greek and Roman men with quoted
      dates of birth and death has been compared statistically with three sample
      populations from different periods. It was found that the ancients who were born
      before 100 BC lived as long as the moderns who died before 1950; they lived
      significantly shorter lives than those who have died in the present half century.

PMID- 8308826
TI  - Darwinian aftershocks: repercussions in late twentieth century medicine.

PMID- 8308827
TI  - A history of physical activity, health and medicine.

PMID- 8308828
TI  - Changes in locomotor function, complementary medicine and the general
      practitioner.

PMID- 8308829
TI  - The medical museum and its relevance to modern medicine.

PMID- 8308830
TI  - Body builder's liver.

PMID- 8308831
TI  - Ergot induced myocardial ischaemia in a patient without vasospastic disorder.

PMID- 8308832
TI  - Tuberculous fissure-in ano.
AB  - Anal tuberculosis is rare, with cases appearing sporadically in the worldwide
      literature, and only a single case report of the condition occurring in the UK
      over the last 10 years. We are able to present a case of tuberculous fissure-in
      ano.

PMID- 8308833
TI  - The American health care system: a perspective from a visiting British general
      practitioner.

PMID- 8308834
TI  - Cervical dorsal column stimulation relieves pain of brachial plexus avulsion.
AB  - Five patients with deafferentation pain due to brachial plexus avulsion injuries
      were treated with cervical dorsal column stimulation (DCS). This has produced a
      clinically useful improvement in pain relief and mood scores during a mean follow
      up period of 13.5 months. No complications have been encountered and the
      advantages of DCS are discussed.

PMID- 8308835
TI  - Compartments of medicine.

PMID- 8308836
TI  - Increasing role of MRI in the investigation of spinal osteomyelitis.

PMID- 8308837
TI  - Monsieur Andry's proposition.

PMID- 8308838
TI  - Europe and the tropics--how benevolence can lead to disaster.

PMID- 8308839
TI  - Squint--an etiological marker in microcephaly.

PMID- 8308840
TI  - The use of acyclovir in suspected encephalitis.
AB  - The early use of intravenous acyclovir in herpes simplex encephalitis (HSE) is
      essential. However, rapid diagnostic tests are not freely available. Hence, all
      patients with suspected encephalitis may need to be commenced on acyclovir. In
      our study, of 34 patients with suspected encephalitis, only two eventually had
      HSE confirmed, 19 had encephalitis not due to herpes simplex and in 13 a non
      encephalitis illness was finally diagnosed. Guidelines for the use of acyclovir
      in suspected encephalitis are given aimed at minimizing the drug cost whilst
      still protecting all cases of presumed HSE.

PMID- 8308841
TI  - Susceptibility of Helicobacter pylori to the antibacterial activity of manuka
      honey.
AB  - Honey is a traditional remedy for dyspepsia, and is still used for this by some
      medical practitioners although there is no rational basis for its use. The
      finding that Helicobacter pylori is probably the causative agent in many cases of
      dyspepsia has raised the possibility that the therapeutic action of honey may be
      due to its antibacterial properties. Consequently, the sensitivity of
      Helicobacter pylori to honey was tested, using isolates from biopsies of gastric
      ulcers. It was found that all five isolates tested were sensitive to a 20% (v/v)
      solution of manuka honey in an agar well diffusion assay, but none showed
      sensitivity to a 40% solution of a honey in which the antibacterial activity was
      due primarily to its content of hydrogen peroxide. Assessment of the minimum
      inhibitory concentration by inclusion of manuka honey in the agar showed that all
      seven isolates tested had visible growth over the incubation period of 72 h
      prevented completely by the presence of 5% (v/v) honey.

PMID- 8308842
TI  - Diagnosis of HIV in babies of HIV-infected mothers.

PMID- 8308843
TI  - Medical counselling and patient compliance in Turkish and Greek speaking
      communities in Haringey and Enfield.

PMID- 8308844
TI  - A study of the impact of Arabic coffee consumption on serum cholesterol.
AB  - Consumption of Arabic coffee is commonly practised by Saudi citizens. The present
      study was conducted to explore the possible relationship between the serum total
      cholesterol levels and the intake of Arabic coffee. A total of 252 adult Saudi
      individuals were recruited, of whom 143 were coffee drinkers and 109 did not
      drink coffee. The study showed that in comparison to the non-coffee drinkers the
      serum total cholesterol concentration was significantly higher among the coffee
      drinkers. Furthermore, the level was higher among females than males who were
      coffee drinkers. The effect of the duration of coffee consumption on the serum
      total was significant for both sexes (P < 0.001). It is suggested that further
      studies should be generated in order to address questions related to the issues
      discussed. At the present time a reduction in coffee consumption by those groups
      found to be more liable to adverse influence on their serum total cholesterol
      levels to have a positive influence should be considered.

PMID- 8308845
TI  - Arena tests with piperonal, a new louse repellent.
AB  - Piperonal, once used to kill lice in Australian hospitals, was acclaimed as an
      effective pediculicide (Corlette, 1925) by the standards of the day. It is
      unusual in also exhibiting a repellent action against lice, a property only
      recently realised. A new, easy to use, low-fragrance, pump action spray, which
      incorporates 2% piperonal, was tested in the laboratory using clothing lice in an
      arena test and was found to exhibit consistently high repellency after half an
      hour, dropping only slightly after 24 hours. A well known multi-purpose insect
      repellent, diethyltoluamide (DEET), was then tested against piperonal. A 2%
      solution of piperonal was found to be almost twice as effective as a 50% solution
      of DEET. In arena tests using lice with the tip segments of both antennae
      removed, no behavioural differences or statistically significant differences from
      a random distribution could be found between untreated and Rappell-treated areas.
      This strongly suggests that sense organ(s) on the tip of the antenna are
      necessary for detection of the repellent. Although there can be no strict
      correlation between results in the laboratory and potential efficacy in the
      field, materials such as insecticides found to be effective in the laboratory
      have been found to be equally effective in the field. Furthermore, what with the
      threat of resistance to head lice insecticides, ineffectual treatment and the
      lack of contact tracing, a repellent would be of obvious use in the control of
      head lice.

PMID- 8308846
TI  - National recording of environmental incidents in Scotland.
AB  - One of the main problems in determining the environmental status of a territory
      is the common failure to accurately record the occurrence of environmental
      incidents. All too often control of pollution is the responsibility of various
      independent central and local government departments without overall cooperation
      and recording of incidents. If an official recording mechanism is not in place no
      determination of the number of environmental incidents that occur in a given
      period of time can be determined, no relation of connected incidents can be made,
      no lessons can be learned and passed on to all those working in the pollution
      control field, and no assessment of improved environmental standards can be
      achieved. In Scotland for the past 3 years a central system for recording
      environmental health incidents has been in place and many benefits from this
      administrative arrangement are already evident. The implementation, management
      benefits and results obtained from the programme are given and suggestions are
      made as to how this programme could be extended internationally.

PMID- 8308847
TI  - Smoking habits among physicians in two Gulf countries.
AB  - The smoking habit of physicians in United Arab Emirates (UAE) and Kuwait were
      studied as first step towards surveying the habit among medical professionals. A
      cross-sectional survey was conducted in Kuwait between January-June 1990. Out of
      the 300 physicians who were contacted 252 (84%) completed the questionnaires, 190
      (75%) were males and 62 (25%) were females. Among male physicians, current
      smokers were 86 (45.3%), ex-smokers were 34 (17.9%) and non-smokers were 70
      (36.8%), while among the female physicians 10 (16%) were smokers and 52 (84%)
      were non-smokers. Also, a cross-sectional study was conducted between December
      1991-November 1992 to identify the extent of smoking among physicians in UAE. Of
      the 300 physicians, 275 (91.6%) responded, 214 (77.8%) were males and 61 (22.2%)
      were females. Among the males, current smokers were 94 (43.9%), ex-smokers were
      32 (14.9%) and non-smokers were 88 (41.2%), while among the females 5 (8.2%) were
      smokers, 3 (4.9%) were ex-smokers and 53 (86.9%) were non-smokers. Most important
      factors responsible for non-smoking doctors for not taking up smoking were:
      'Protection of health', 'Self-discipline' and 'To set a good example to others'.
      The majority of physicians in UAE (91.3%) and Kuwait (75.6%) strongly agreed that
      smoking is hazardous to health. The results revealed that less than 50% of
      physicians provide information to over 70% of smoking patients. The majority of
      physicians and health professionals were aware of association between smoking and
      various diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8308848
TI  - A comparison of community pharmacists' and general practitioners' opinions on
      rational prescribing, formularies and other prescribing related issues.
AB  - A postal survey of Community Pharmacists (CPs) and General Medical Practitioners
      (GPs) in the Enfield and Haringey (E&H) and North Yorkshire (N Yorks) Family
      Health Services Authority (FHSA) areas was carried out to investigate: a. their
      opinions regarding clinically oriented 'extended' roles for CPs, and the
      possibility of interprofessional collaboration on them, and b. their views on a
      range of prescribing related issues. The overall response rate was 67% for CPs
      and 42% for GPs. There were no significant differences in responses to questions
      between CPs in both FHSAs, but significant differences in answers to some
      questions between the two groups of GPs, due to a large proportion of dispensing
      GPs in N Yorks. Results were therefore expressed as comparisons between total
      numbers of CPs and GPs, and between dispensing and non-dispensing GPs. The
      results showed an affinity of outlook between CPs and GPs on a range of
      prescribing related issues, and considerable goodwill between the two groups on
      which future cooperation could be founded. GPs were, however, significantly less
      enthusiastic than CPs about collaboration in areas which would concede a role to
      CPs in making prescribing decisions. GPs were most favorably disposed to
      collaboration in areas such as the provision of drug information, which could be
      considered as within GPs' domain of specialist expertise.

PMID- 8308849
TI  - Rapid assessment of environmental radon levels.
AB  - Radon is an important potential cause of cancer but this hazard is preventable. A
      rapid means of assessing the concentration of radon occurring in an area is
      described. The method requires only simple robust equipment to determine if there
      is a significant problem needing further detailed research. Results obtained in
      Cornwall by this method are shown to illustrate the potential for the procedure.

PMID- 8308850
TI  - Environmental health in remote aboriginal communities.

PMID- 8308851
TI  - Restorative dental care of the geriatric patient.
AB  - Dental care of the elderly generally does not form a major area of study in the
      undergraduate curriculum, and seldom forms the main attraction at dental
      conferences. All too often treatment of the elderly is considered to be a
      backwater of prosthetic dentistry and little attention is paid to the restorative
      needs of this rapidly growing section of society. The aim of this paper is to
      identify the dental needs of an ageing population, and to focus the attention of
      the profession on these needs as well as to explore certain myths and prejudices
      associated with the treatment of patients in senescence.

PMID- 8308852
TI  - Food safety: an appraisal of a training programme.

PMID- 8308853
TI  - Playground safety.

PMID- 8308854
TI  - Nutritional quality--a contract caterer's perspective.

PMID- 8308855
TI  - Joint hyperlaxity and its long-term effects on joints.
AB  - The range of movement at a joint varies between individuals. Reasons for this
      include inherited collagen structure in the joint capsule and ligaments,
      inherited shape of the bony articulating surfaces and neuromuscular tone which
      may be acquired and is modified by training. Methods for quantifying the range of
      movement at joints are described and compared, including the hyperextensometer
      and the Carter and Wilkinson score. Clinical patterns of joint hyperlaxity and
      their correlation with aetiology are discussed. Joint hyperlaxity may be
      advantageous in certain sports. Coaches need to be aware of optimum methods for
      improving it as well as for guarding against injury. Conversely, physiotherapists
      may learn from sports physiologists in the management of symptoms arising from
      patients who have hyperlax joints. Joint stability reduces the risk of injury.
      Joint hyperlaxity may also be associated with premature osteoarthritis but this
      is not always so. Joint instability may be the most potent cause though a
      radiological survey of retired teachers of physical education conducted by our
      Unit failed to show a higher incidence of osteoarthritis after a life spent in
      sport than in sedentary controls. However, certain factors that place some
      individuals at particular risk were identified.

PMID- 8308856
TI  - Public health in the United States.

PMID- 8308857
TI  - The discovery of sulfonamide endothelin antagonists and the development of the
      orally active ETA antagonist 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1
      naphthalenesulf onamide.

PMID- 8308858
TI  - A new potent and selective histamine H3 receptor agonist, 4-(1H-imidazol-4
      ylmethyl)piperidine.

PMID- 8308859
TI  - Enzyme-activated antagonists of the strychnine-insensitive glycine/NMDA receptor.

PMID- 8308860
TI  - Rational modification of human synovial fluid phospholipase A2 inhibitors.

PMID- 8308861
TI  - Substituted O6-benzylguanine derivatives and their inactivation of human O6
      alkylguanine-DNA alkyltransferase.
AB  - Several new O6-benzylguanine analogs bearing increasingly bulky substituent
      groups on the benzene ring or at position 9 were tested for their ability to
      inactivate the human DNA repair protein, O6-alkylguanine-DNA alkyltransferase.
      Substitution on the benzene ring was well tolerated although activity varied
      considerably with structural changes in groups attached to position 9. For this
      site, activity was preserved with large or small lipophilic groups while
      introduction of non-carbohydrate polar groups generally reduced activity
      regardless of their size.

PMID- 8308862
TI  - Design, synthesis, and in vitro activity of bis(succinimido)hexane peptide
      heterodimers with combined B1 and B2 antagonist activity.
AB  - We have developed a series of peptide heterodimers based on the B2 antagonist D
      Arg0-[Hyp3,D-Phe7,Leu8]-BK (1) and the B1 antagonist Lys0-[Leu8,des-Arg9]-BK (7)
      that are potent antagonists of both B1 and B2 receptors. From this series,
      compound 50 (alternatively, CP-0364), the 1,6-bis(succinimido)hexane heterodimer
      of D-Arg0-[Hyp3,Cys6,D-Phe7,Leu8]-BK (2), and D-Arg0-[Cys1,Hyp3,Leu8,des-Arg9]-BK
      (6), was found to be the most active both in vitro and in vivo. Compound 50 has a
      pA2 of 8.3 when measured against bradykinin (BK)-induced rat uterine smooth
      muscle contraction and an IC50 of approximately 10(-8) M against [des-Arg9]-BK
      induced rabbit aorta smooth muscle contraction in vitro. Compounds such as 50 may
      be useful in the treatment of both subacute and chronic inflammatory disorders
      wherein both B2 and B1 receptors appear to contribute to the clinical
      manifestations of the disease.

PMID- 8308863
TI  - Relationships between structure and kinetics of cyclization of 2-aminoaryl
      amides: potential prodrugs of cyclization-activated aromatic mustards.
AB  - 2-Nitroaryl amides of general structure I are proposed as bioreducible prodrugs,
      capable of releasing cytotoxic aminoaniline mustards V on bioactivation by
      spontaneous cyclization of the resulting 2-aminoarylamides II via a tetrahedral
      intermediate, III. This concept allows separate optimization of the substituent
      effects influencing nitro-group reduction and mustard reactivity. A series of
      model 2-aminoaryl amides has been synthesized, and their rates of cyclization
      have been studied; these varied by a factor of more than 50,000-fold (kobs from
      0.00040 to 21 min-1) at pH 2.4. For three compounds studied in detail, the rates
      were linearly dependent of pH, indicating that no change in the mechanism of the
      rate-determining step occurs over the pH range studied. The nucleophilicity of
      the amino group had a modest influence on the kinetics of cyclization, with
      electron-withdrawing groups slowing the rate. The geometry of the compound was
      also important, with structure-activity relationships indicating that the rate of
      cyclization is greatly enhanced by the preorganization of the molecule. In
      contrast, 4-substitution on the leaving aniline by a variety of groups had little
      effect on the cyclization reaction. These results are consistent with the rate
      determining step being formation of the tetrahedral intermediate. These model
      studies suggest that the phenyldimethylacetamide system could be developed as a
      prodrug system for the bioreductively-triggered release of amines. Further
      substantial rate enhancements appear possible by alterations in the geometry of
      the system, whereas substitution of electron-withdrawing groups (required to
      raise the nitro-group reduction potential into the appropriate range) has only
      relatively modest retardation effects on rates of cyclization. More rigid systems
      may also be useful; a nitronaphthaleneacetamide analogue cyclized spontaneously
      during nitro-group reduction, suggesting a very short half-life for the reduced
      intermediate (amine or hydroxylamine).

PMID- 8308864
TI  - Hypoxia-selective antitumor agents. 8. Bis(nitroimidazolyl)alkanecarboxamides: a
      new class of hypoxia-selective cytotoxins and hypoxic cell radiosensitisers.
AB  - A series of novel bis(nitroimidazolyl)alkanecarboxamides has been prepared and
      evaluated for hypoxia-selective cytotoxicity and hypoxic cell radiosensitisation
      in vitro and in vivo. The compounds were prepared by direct coupling of preformed
      side chain acid and amine components, using diethyl phosphorocyanidate at room
      temperature. Although designed to be bis-bioreductive prodrugs of DNA cross
      linking agents, none of the compounds showed evidence of DNA cross-linking
      activity, being equally potent against cell lines deficient and proficient in
      repair of cross-links. However, one of these compounds, N-[2-(2-methyl-5-nitro-1H
      imidazolyl)ethyl]-4-(2-nitro-1H- imidazolyl)butanamide (10; SN 24699), showed
      high hypoxic selectivity as a cytotoxin (rising to 200-fold after exposure to the
      drug for several hours) in the repair-proficient Chinese hamster cell line AA8.
      This selectivity was greater than observed for the alkylating 2-nitroimidazole
      (4; RB 6145) (40-fold) or simple mononitroimidazoles (5-25-fold). Investigation
      of structure-activity relationships for hypoxic selectivity of
      bis(nitroimidazoles) was restricted by their low aqueous solubility, but a
      certain minimum separation of the two nitroimidazole units (by more than five
      atoms) appears desirable. All the compounds radiosensitized hypoxic cells in
      vitro but were little more potent as radiosensitizers than the corresponding
      monomeric nitroimidazoles. Compound 10 caused additional cell killing in the KHT
      tumor when multiple drug doses were administered in combination with a single
      dose of radiation. It is not yet clear whether this activity reflects hypoxic
      cell radiosensitization or cytotoxicity toward hypoxic cells, but this new class
      of bis-bioreductive agent clearly warrants further investigation.

PMID- 8308865
TI  - CNAD: a potent and specific inhibitor of alcohol dehydrogenase.
AB  - CNAD (5-beta-D-ribofuranosylnicotinamide adenine dinucleotide) is an isosteric
      and isomeric analogue of NAD, in which the nicotinamide ring is linked to the
      sugar via a C-glycosyl (C5-C1') bond. CNAD acts as a general dehydrogenase
      inhibitor but shows unusual specificity and affinity for liver alcohol
      dehydrogenase (ADH, EC 1.1.1.1). The pattern of inhibition is congruent to 4 nM,
      with NAD as the variable substrate. These values are 3-5 orders of magnitude
      smaller than those obtained for CNAD in other dehydrogenases and are comparable
      to values observed for the tightest binding ADH inhibitors known. The specificity
      and affinity of CNAD for ADH are likely due to coordination of the zinc cation at
      the ADH catalytic site by the CNAD pyridine nitrogen. This is supported by
      kinetic and computational studies of ADH-CNAD complexes. These results are
      compared with those for a related analogue, CPAD. In this analogue, displacement
      of the pyridine nitrogen to the opposite side of the ring removes the specificity
      for ADH.

PMID- 8308866
TI  - Dual-action cephalosporins incorporating a 3'-tertiary-amine-linked quinolone.
AB  - We have previously reported that linking quinolones to the cephalosporin 3'
      position through an ester bond, a carbamate function, or a bond through a
      quaternary nitrogen produced cephalosporins with a dual mode of antibacterial
      action. We now describe a new class of dual-action cephalosporins, with greater
      chemical stability than those previously reported, in which the basic nitrogen of
      ciprofloxacin is bonded directly to the 3'-cephalosporin position, i.e., the two
      moieties are linked through a tertiary amine function. These compounds have
      demonstrated potent activity against a broad spectrum of Gram-positive and Gram
      negative bacteria, including beta-lactam-resistant strains.

PMID- 8308867
TI  - Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application
      for identifying retinoids with unusual binding properties.
AB  - all-trans-Retinoic acid is known to bind to the retinoic acid receptors (RARs)
      resulting in an increase in their transcriptional activity. In contrast, recently
      identified 9-cis-retinoic acid (9-cis-RA), which is an additional endogenous RA
      isomer, is capable of binding to both RARs and retinoid X receptors (RXRs). These
      distinct properties have raised questions as to the biological role governed by
      these two retinoic acid isomers and the set of target genes that they regulate.
      Herein, we report the synthesis of high specific activity [3H]-9-cis-RA and its
      application to study the ligand-binding properties of the various retinoid
      receptor subtypes. We examined the binding properties of RARs and RXRs for a
      series of synthetic retinoids and compared the ligand-binding properties of these
      arotinoid analogs with their ability to regulate gene expression via the retinoid
      receptors in a cotransfection assay. The utilization of the [3H]-9-cis-RA
      competitive binding assay and the cotransfection assay has made it possible to
      rapidly identify important structural features of retinoids leading to increased
      selectivity for either the RAR or RXR receptor subtypes.

PMID- 8308868
TI  - Synthesis and photodynamic activities of silicon 2,3-naphthalocyanine
      derivatives.
AB  - Bis(tert-butyldimethylsiloxy)- (7), bis(dimethylthexylsiloxy)- (8), bis(tri-n
      hexylsiloxy)- (9), and bis(dimethyloctadecylsiloxy)silicon 2,3-naphthalocyanines
      (10) were prepared via substitution of the bis(hydroxy) precursor with the
      corresponding chlorosilane ligands and characterized by spectroscopic and
      combustion analyses. They show strong absorption around 780 nm where tissues
      exhibit optimal transparency. Compounds 7-10 are capable of producing singlet
      oxygen. They are relatively photostable although less stable than the analogous
      phthalocyanine, i.e., the bis-(dimethylthexylsiloxy)silicon phthalocyanine (12).
      They were evaluated as potential photosensitizers for the photodynamic therapy
      (PDT) of cancer in vitro against V-79 cells and in vivo against the EMT-6 tumor
      in Balb/c mice. In vitro all four dyes showed limited phototoxicity combined with
      substantial dark toxicity. Surprisingly, in vivo (i.v., 0.1 mumol/kg, 24 h prior
      to the photoirradiation of the tumor with 780-nm light, 190 mW/cm2, 400 J/cm2)
      all dyes induced tumor regression in at least 50% of mice whereas compound 8 gave
      a complete tumor response in 80% of mice without apparent systemic toxicity at
      doses as high as 10 mumol/kg. At 24 h postinjection, compound 8 showed a
      favorable tumor to muscle ratio of 7, assuring minimal damage to the healthy
      tissue surrounding the tumor during PDT. Our data confirm the potential of
      silicon naphthalocyanines as far-red-shifted photosensitizers for the PDT of
      cancer and indicate the importance of the selection of the two axial silicon
      ligands for optimal photodynamic efficacy.

PMID- 8308869
TI  - Selective protection and relative importance of the carboxylic acid groups of
      zaragozic acid A for squalene synthase inhibition.
AB  - Chemistry that allows selective modification of the carboxylic acid groups of the
      squalene synthase inhibitor zaragozic acid A (1) was developed and applied to the
      synthesis of compounds modified at the 3-,4-,5-,3,4-,3,5-, and 4,5-positions. A
      key step in this procedure is the selective debenzylation by transfer
      hydrogenolysis in the presence of other olefinic groups. These compounds were
      tested in the rat squalene synthase assay and in vivo mouse model. Modification
      at C3 retains significant enzyme potency and enhances oral activity, indicating
      that C3 is not essential for squalene synthase activity. Modification at C4 and
      C5 results in significant loss in enzyme activity. In contrast, substitution at
      C3 or C4 enhances in vivo activity. Furthermore, disubstitution at the C3 and C4
      positions results in additive in vivo potency.

PMID- 8308870
TI  - Isosteric phosphonate analogs of ET-16-OMe. Synthesis and biological evaluation
      of the enantiomers of 2'-(trimethylammonio)ethyl 4-(hexadecyloxy)-3
      methoxybutanephosphonate and 2'-(trimethylammonio)ethyl 4-(hexadecylthio)-3
      methoxybutanephosphonate.
AB  - The enantiomers of two isosteric phosphonate analogs of the ether-linked
      antitumor agent 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OMe)
      were synthesized and evaluated for their cytotoxicity against various mouse
      leukemic cell lines in vitro and in vivo. The key step in the synthesis of the
      alkyloxy and alkylthio analogs (1 and 2, respectively) is the opening of an
      epoxide [hexadecyl 2-oxiranylmethyl ether (4) or hexadecyl 2-oxiranylmethyl
      thioether (8)] by LiCH2P(O)(OMe)2 using BF3.Et2O in tetrahydrofuran at low
      temperature. The cytotoxic activities of the hexadecyloxy and hexadecylthio
      phosphonate analogs of ET-18-OMe (1 and 2) against the murine leukemias WEHI
      3B,L1210, and P388 were similar, indicating that substitution of a sulfur atom
      for oxygen in the long-chain ether does not result in a significant difference in
      cytotoxicity. The IC50 values of 1 and 2 were in the range of 1-5 microM.
      Alkyloxy phosphonate 1 was highly effective in inhibiting the growth of WEHI-3B
      and P388 tumors implanted in BALB/C mice. The alkyloxy and alkylthio phosphonates
      1 and 2 prolonged the survival of CD1 mice bearing L1210 tumors. The antitumor
      activities of the phosphonate analogs of ET-18-OMe in these in vitro and in vivo
      studies were independent of chirality, consistent with previous studies with the
      enantiomers of 1-O-hexadecyl-2-O-methyl-sn-glycero-3-phosphocholine.

PMID- 8308871
TI  - Autonomy, respect for autonomy and weakness of will.

PMID- 8308872
TI  - Demystifying bioethics--a lay perspective.

PMID- 8308873
TI  - Deciding not to resuscitate in Dutch hospitals.
AB  - The use of do not resuscitate (DNR) orders in Dutch hospitals was studied as part
      of a nationwide study on medical decisions concerning the end of life. DNR
      decisions are made in 6 per cent of all admissions, and 61 per cent of all in
      hospital deaths were preceded by a DNR decision. We found that in only 14 per
      cent of the cases had the patients been involved in the DNR decision (32 per cent
      of competent patients). The concept of futility is analysed as these findings are
      discussed. We conclude that determining the effectiveness of resuscitation is a
      medical judgement whereas determining the proportionality (burden/benefit ratio)
      of it requires a discussion between doctor and patient (or his or her
      surrogates). Since the respondents in the cases without patient involvement gave
      many reasons for their decision that went beyond determining effectiveness, we
      conclude that more patient involvement would have been desirable.

PMID- 8308874
TI  - Autonomy and the akratic patient.
AB  - I argue that the distinction which is current in much writing on medical ethics
      between autonomous and non-autonomous patients cannot cope comfortably with weak
      willed (incontinent) patients. I describe a case involving a patient who refuses
      a blood transfusion even though he or she agrees that it would be in his or her
      best interests. The case is discussed in the light of the treatment of autonomy
      by B Brody and R Gillon. These writers appear to force us to treat an incontinent
      patient either as autonomous, just like a rational agent whose decisions are in
      accordance with his beliefs or as non-autonomous, like comatose patients or
      children. Though neither is entirely satisfactory I opt for describing such
      patients as autonomous but point out that in cases like this the principle of
      respect for autonomy does not give a determinate answer about how the patient
      ought to be treated.

PMID- 8308875
TI  - Clinical trials: two neglected ethical issues.
AB  - Ethical reasons are presented for requiring 1) that a proposal for a clinical
      trial should be accompanied by a thorough review of all previous trials that have
      examined the same and closely related questions, and 2) that a trial should be
      approved by a research ethics committee only if the investigator undertakes to
      register it in an appropriate register of clinical trials as soon as one exists.

PMID- 8308876
TI  - Neonatal extracorporeal membrane oxygenation (ECMO): clinical trials and the
      ethics of evidence.
AB  - Neonatal extracorporeal membrane oxygenation (ECMO), a technology for the
      treatment of respiratory failure in newborns, is used as a case study to examine
      statistical and ethical aspects of clinical trials and to illustrate a proposed
      'ethics of evidence', an approach to medical uncertainty within the context of
      contemporary biomedical ethics. Discussion includes the twofold aim of the ethics
      of evidence: to clarify the role of uncertainty and scientific evidence in
      medical decision-making, and to call attention to the need to confront the
      irreducible nature of uncertainty.

PMID- 8308877
TI  - Ethics and statistical methodology in clinical trials.
AB  - Statisticians in medicine can disagree on appropriate methodology applicable to
      the design and analysis of clinical trials. So called Bayesians and frequentists
      both claim ethical superiority. This paper, by defining and then linking together
      various dichotomies, argues there is a place for both statistical camps. The
      choice between them depends on the phase of clinical trial, disease prevalence
      and severity, but supremely on the ethics underlying the particular trial. There
      is always a tension present between physicians primarily obligated to their own
      patients (the weight of 'individual ethics') and ethical committees responsible
      for the scientific merit of the trial and its long-term implications ('collective
      ethics'). Individual ethics, it is proposed, favour the Bayesian approach;
      collective ethics, the frequentist. Though in some situations the choice appears
      clear-cut, there remain other where both methodologies can be appropriate.

PMID- 8308878
TI  - The nurse under physician authority.
AB  - A medical centre is an institution established for a specific purpose: to
      facilitate the health and health-related welfare of the medical centre's
      patients. Within this institution, there are a variety of professionals who act
      and interact to serve this purpose. Of particular interest is the interaction
      between physician and nurse. Generally, the nurse is thought to be under a
      certain obligation to implement a physician's orders unless there is good reason
      not to do so. This qualifier places a conflicting obligation upon the nurse not
      to implement some physician orders. How should a judgement about which orders
      there is 'good reason' not to implement be made? I propose to approach this
      question through an analysis of the obligation the nurse has to implement the
      order of a physician, and the conditions under which the order does not pose such
      obligations. This analysis will consist of an examination of the obligation in
      terms of the purposive authority of the physician. For example, in the context of
      the medical centre, the physician's medical training qualifies her as best able
      to make determinations of what treatment would promote the patient's health.
      However, this purpose not only serves as the basis of the physician's authority,
      but also serves as a limitation upon the physician's authority (for example, an
      order which would harm the patient would not reflect the purpose for which the
      physician has been given authority). Thus, a philosophical investigation into the
      nature of the obligation to implement a physician's orders can help to clarify
      those occasions when a nurse should not implement an order.

PMID- 8308879
TI  - Assessing the clinical ethical competence of undergraduate medical students.
AB  - At the University of Newcastle, health law and ethics is taught and assessed in
      each year of the five-year curriculum. However, the critical question for
      assessment remains: 'Does teaching ethics have a measurable effect on the
      clinical activity of medical students who have had such courses?' Those
      responsible for teaching confront this question each year they sit down to
      construct their assessment tools. Should they assess what the student knows?
      Should they assess the student's moral reasoning, that is, what decisions the
      student makes, and, how these decisions are justified, or should they assess what
      the student actually does when dealing with patients in the clinical setting, and
      how he or she does it? From 1982 to 1991, assessment at Newcastle was primarily
      aimed at determining the quality of the students' ethics knowledge base. This
      paper describes the strengths and limitations of a purely knowledge-based method
      of evaluation and why in 1992, we are now attempting to redefine and assess, what
      we call 'clinical ethical competence' in terms of how students actually apply
      this knowledge base in a controlled clinical context.

PMID- 8308880
TI  - Is medical ethics lost? Response 1.

PMID- 8308881
TI  - Is medical ethics lost? Response 2.

PMID- 8308882
TI  - Resuscitation policy.

PMID- 8308883
TI  - Analysis of RNA chain elongation and termination by Saccharomyces cerevisiae RNA
      polymerase III.
AB  - When Saccharomyces cerevisiae RNA polymerase (Pol) III transcribes the S.
      cerevisiae SUP4 tRNA(Tyr) gene, it is obliged to navigate past a large, multi
      subunit DNA-bound complex of proteins. We have analyzed individual steps of RNA
      chain elongation on this gene. Slow steps of transcriptional initiation were by
      passed by forming 5'-end-labeled, arrested and precisely positioned transcription
      complexes. Synchronous resumption of chain elongation by these complexes allowed
      a single round of RNA synthesis and termination to be analyzed in detail. Results
      for synthesis at 20 degrees C and 0 degrees C, in the presence of 100 microM and
      1 mM ribonucleoside triphosphates (NTPs) are presented. RNA chain elongation
      through assembled transcription complexes was uneven but relatively rapid: at 20
      degrees C with 1 mM NTPs, the fastest RNA chains elongated at an average rate of
      29 nucleotides (nt)/second, and the median RNA chains elongated at 21 to 22
      nt/second on average. These rates are comparable with a recent measurement of the
      average rate of chain elongation in vivo by Drosophila RNA polymerase II at 25
      degrees C. At 0 degree C, RNA chain elongation rates were, on average,
      approximately 30-fold slower. Quantitative analysis of the individual steps of
      RNA chain elongation showed that steps of adding U and A to U-terminated RNA
      chains tended to be relatively slow, and to be more strongly influenced by
      nucleotide concentration. Termination of transcription occurred in the sequence
      T7GT6 (in the non-template DNA strand) and was progressive. Transcripts with
      five, six and seven U residues were formed, and there was even slow readthrough
      of the T7 stretch, with GU3 adding rapidly, suggesting that incorporation of a
      single G into the RNA chain served to reset elongation rates substantially or
      entirely. Stripping transcription factor (TF) IIIC from transcription complexes
      did not substantially increase overall RNA chain growth rate, but did diminish
      pausing at a single site upstream of the boxB binding site of TFIIIC. The TFIIIC
      generated delay at this single site was estimated to be only approximately 0.15
      to 0.2 seconds at 20 degrees C. Quantitative analysis of RNA chain elongation
      yielded kinetic parameters for the individual steps of nucleotide addition that
      were used in computer simulations of RNA chain growth. Elongation modeled as a
      simple sequence of pseudo-first-order reactions yielded computed RNA chain length
      distributions that remained relatively synchronous during elongation, while
      observed chain growth quickly became desynchronized.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8308884
TI  - Encounters of Saccharomyces cerevisiae RNA polymerase III with its transcription
      factors during RNA chain elongation.
AB  - The analysis of RNA chain elongation by Saccharomyces cerevisiae RNA polymerase
      (Pol) III in the accompanying paper has been extended by examining the encounter
      of highly purified RNA polymerase with purified individual transcription factors.
      Arrested ternary transcription complexes were formed with purified Pol III
      initiating precisely at the 3' overhanging ends of linear DNA. Transcription
      factors were then bound to DNA and their effects on individual steps of RNA chain
      elongation were analyzed. The outcome of the encounter between Pol III and TFIIIC
      was orientation-specific. For RNA synthesis in the sense direction, with Pol III
      approaching the obstructing protein from the direction of normal transcription,
      pure TFIIIC rapidly yielded the way to the advancing polymerase: only a single
      step of RNA chain elongation was slightly slowed by pure TFIIIC occupying its
      boxB binding site in the SUP4 tRNA(Tyr) gene. In a complete cell-free fraction,
      protein binding to this tRNA gene likewise generated a delay of only
      approximately 0.15 to 0.2 second in executing the same step. Transcription by
      pure Pol III in the sense direction also dissociated the TFIIIC-SUP4 gene
      complex. The encounter of Pol III elongating RNA chains in the anti-sense
      direction with the backside of TFIIIC yielded a different outcome. RNA chain
      elongation paused extensively six to nine base-pairs beyond the downstream edge
      of the DNA-binding site of TFIIIC, with a median delay of nine seconds,
      approximately 50 times longer than in the sense direction. At the height of its
      effect on RNA chain elongation, the TFIIIC-imposed barrier entrapped the great
      majority of RNA chains, but their elongation was eventually allowed to continue.
      In contrast, DNA-bound TFIIIB completely blocked RNA chain elongation in the anti
      sense direction. The role of the internal promoter element in transcription by
      Pol III is discussed in the light of this analysis. The large bulk of TFIIIC,
      which binds with high affinity to boxB, and also to boxA, is particularly suited
      to occluding its transcription unit to other proteins. At the same time, TFIIIC
      makes way for transcription so rapidly that it places no limit on the level of
      gene activity.

PMID- 8308886
TI  - The human calbindin-D9k gene. Complete structure and implications on steroid
      hormone regulation.
AB  - The gene encoding the human calbindin-D9k has been cloned and the complete
      sequence established. The gene spans about 5.5 kilobases and is localized on the
      X-chromosome, consists of three exons and carries four Alu repeats. The promoter
      and 1300 base-pairs of 5' flanking region have been characterized. Besides a TATA
      box and two CAAT-like motifs a sequence related to a vitamin D response element
      was detected about 1.1 kilobases upstream from the promoter. A sequence
      positioned 50 nucleotides downstream from the promoter showed extensive homology
      to the estrogen response element at the same location within the rat calbindin
      D9k gene. Two essential nucleotides within this region are changed when the rat
      and human sequences are compared. The human element failed to bind the estrogen
      receptor as determined by gel retardation assay. It is proposed that a two
      nucleotide change within this region causes the gene to lack expression in human
      uterus and possibly placenta.

PMID- 8308885
TI  - Conformational drug determinants of the sequence specificity of drug-stimulated
      topoisomerase II DNA cleavage.
AB  - To gain further knowledge of the molecular features of topoisomerase II
      inhibitors required for drug-receptor complex formation, we investigated the
      conformational drug determinants of the sequence specificities of drug-stimulated
      DNA cleavage by computer-aided molecular modeling techniques. DNA sequence
      specificities of bisantrene, genistein, piroxantrone and ellipticinium were
      determined by using simian virus 40 DNA and compared to those of mitoxantrone, 4
      demethoxydaunorubicin, VM-26 and mAMSA. DNA cleavage intensity patterns of
      bisantrene and mAMSA were virtually identical in sequencing gels, although these
      drugs are of distinct chemical classes. Genistein and ellipticinium showed drug
      specific DNA cleavage intensity patterns with no apparent similarity to other
      drugs or to each other. From 54 to 72 drug-stimulated sites were sequenced, and
      local base sequence specificities were established by statistical analyses. In
      complete agreement with mAMSA requirements, bisantrene required an adenine at
      position +1. Ellipticinium required a thymine and excluded a cytosine at position
      -1. Genistein was the only drug showing base requirements (thymines) at both
      positions -1 and +1. Piroxantrone (structurally related to mitoxantrone) required
      a pyrimidine at position -1. Since the common sequence specificity of bisantrene
      and mAMSA could not be simply explained by the nature of some chemical
      substituents, a comparative molecular modeling analysis of the drugs was carried
      out based on their steric and electronic attributes. Energy-minimized structures
      of mAMSA and bisantrene were very similar, since their planar aromatic domains
      and pendant side-chains overlapped to a very good approximation. In contrast,
      their most stable conformations were different from other drug structures. In
      particular, the planar system and pendant sugar moiety of doxorubicin, which also
      required an adenine but at position -1, was not superimposed to the corresponding
      moieties of mAMSA and bisantrene even when considering computer-generated
      conformations with higher energy contents. The most stable conformations of the
      other drugs studied revealed specific three-dimensional motifs. Therefore, since
      in a simple model of drug action each spatial region has a single chemical
      pharmacological function, these results suggest that bisantrene and mAMSA share
      common steric and electronic features that may constitute a specific
      pharmacophore. We suggest that the molecular properties of this pharmacophore may
      be critical determinant of the +1 position specificity shown by mAMSA and
      bisantrene.

PMID- 8308887
TI  - Visualization of protein-nucleic acid interactions involved in the in vitro
      assembly of the Escherichia coli 50 S ribosomal subunit.
AB  - Protein-nucleic acid interactions which occur during Escherichia coli 50 S
      ribosomal subunit assembly between 23 S rRNA, 5 S rRNA and a complete set of 34 L
      proteins were monitored by high resolution scanning transmission electron
      microscopy (STEM). This approach made it possible to visualize and quantitatively
      analyze conformational changes induced in the rRNAs during E. coli 50 S ribosomal
      subunit assembly. The reconstituted RNA-protein complexes, the control 23 S rRNA
      and native 50 S subunits were characterized by their mass and morphology.
      Association of 23 S rRNA with the first assembly protein, L24, led to the
      formation of a distinct nucleus of mass ("cluster") on the filamentous and
      loosely coiled molecule of the 23 S rRNA. This structural feature was preserved
      and enhanced in 23 S rRNA after its association with the rest of the early
      assembly proteins, namely L3, L20, L13, L4 and L22. Since the above proteins,
      with the exception of L3, bind to the 5' end of the 23 S rRNA, the cluster seems
      to be formed predominantly by interactions of L24, L13, L20, L22 and L4 with this
      segment of the 23 S rRNA molecule. Association with the rest of the primary
      binding proteins (L2, L23, L9, L1), which interact with the 3' end of the 23 S
      rRNA, appears to result in the formation of a second mass center. Binding of
      additional proteins led to the formation of compact particles with an apparent
      similarity to the 50 S subunit. However, particles with defined structural
      features characteristic of the native 50 S subunit requires the interaction of
      both 23 S rRNA and 5 S rRNA with all of the L-proteins. STEM image analysis
      demonstrated that 50 S subunit reconstitution proceeds by the immediate folding
      of the 23 S rRNA into a single mass center followed by the formation of a second
      mass center. These mass centers merge into one central body, which is gradually
      enhanced and decorated with structural elements characteristic of the 50 S
      subunit in the latter stages of assembly.

PMID- 8308888
TI  - Isolation, characterization and structure of bacterial flagellar motors
      containing the switch complex.
AB  - A putative complex of the three switch proteins, FliG, FliM and FliN appears to
      be directly involved in torque generation and control of direction of rotation.
      We have developed a preparative procedure for flagellar motors that retains these
      proteins as evidenced by Western blots using anti-FliG, anti-FliM and anti-FliN
      antibodies. Immunogold labeling with these three antibodies shows that the three
      switch proteins are localized to the motor. Electron micrographs of frozen
      hydrated preparations reveal a large, new component we have termed the "C ring
      complex" attached to the cytoplasmic face of the M ring. In a three-dimensional
      reconstruction of the cylindrically averaged structure, the M-S ring complex
      appears thicker and wider by the addition of extra material to the cytoplasmic
      surface of the M ring. In addition, extending into the cytoplasm from the
      thickened M ring is the C ring complex, a thin-walled cylinder having a length of
      170 A and an outer diameter of 450 A compared to the 290 A diameter of the M
      ring. We provide evidence that the thickened M ring contains FliG and that the C
      ring complex may contain FliM and FliN. The large diameter of the C ring complex
      may permit interaction with the M ring and with the circlet of studs thought to
      be the MotA/MotB complex.

PMID- 8308889
TI  - conformation and phasing of dystrophin structural repeats.
AB  - The presumptive rod domain of dystrophin contains a series of degenerate
      repeating sequences with homology to those of spectrin. To determine the relation
      of the implied structural repeating units to the sequence repeat (the phasing),
      recombinant fragments of the domain of dystrophin were prepared by expression in
      Escherichia coli. The phasing was established by identifying the minimum sequence
      element that would form a stable fold of high (approx. 75%) alpha-helicity: by
      contrast, incorrectly phased fragments had labile structure with an average alpha
      helicity of about 40%. The isolated folded structural repeat showed high
      stability towards proteolysis and a urea-denaturation profile with a plateau at
      low denaturant concentration, indicative of a unique folded conformation. The
      phasing is consistent with a structure inferred from analysis of the amino acid
      sequence and also found in spectrin, in which each structural repeat comprises a
      three-stranded coiled-coil, made up of one short helix (approx. 30 residues) and
      the N and C-terminal halves of two separate long helices, such that each long
      helix participates in the formation of two contiguous structural units.

PMID- 8308890
TI  - Analysis of repeated motifs in the talin rod.
AB  - The amino acid sequence of the rod portion of talin contains strong periodic
      patterns with a long period of 32 to 34 residues superimposed on short periods of
      7 and 7/2 residues. The rod includes 50 to 60 copies of an irregular repeated
      motif approximately 34 residues long. The motif itself consists of three
      sections: a short "leader" segment of about six residues, which has a high
      proportion of the prolines and acidic residues; a relatively well-conserved
      hydrophobic "core" pattern of approximately 21 residues; and a highly variable
      "linker" region of seven residues which joins onto the next leader. The core
      section sequence has many of the characteristics of an amphipathic helix. The
      extensive hydrophobic side of this postulated helix has a characteristic surface
      pattern of large and small hydrophobic residues (mainly Leu and Ala), with a
      strong periodicity of seven residues. It also has a narrow hydrophilic edge with
      a highly variable sequence. The core sequence is unlike either a normal helical
      coiled coil or a leucine zipper, because it contains several helical ridges and
      grooves. The helical cores probably form a tightly packed hydrophobic central
      strand for the fibrous tail. The leader and linker sections are highly variable
      in length, so that the spacing between the starting points of adjacent cores
      varies between 20 and 40 residues. The most common spacing is 34, and many
      spacings are close to this length.

PMID- 8308891
TI  - Cardiotoxin III from the Taiwan cobra (Naja naja atra). Determination of
      structure in solution and comparison with short neurotoxins.
AB  - The structure in solution of cardiotoxin III, a membrane toxin purified from the
      venom of the Taiwan cobra, Naja naja atra, is reported. Sequence-specific
      assignment of 1H-NMR lines was completed and the NMR data show the presence of a
      triple and a double-stranded antiparallel beta-sheet. Many NOE cross peaks
      identified in NOESY spectra were applied as distance constraints based on a
      hybrid distance geometry/dynamical simulated annealing technique; 20 structures
      were found within a single family. The average value of atomic RMS differences
      between the 20 structures and their geometric mean is 0.087 nm for the backbone
      atoms and 0.152 nm for all heavy atoms; they are 0.055 nm and 0.12 nm,
      respectively for the segments of secondary structure. In these selected
      structures the backbone of the polypeptide chain folds such that five strands
      emerge from a globular head. Three major loops link these strands to form a
      double and a triple-stranded antiparallel beta-sheet. Comparison of the
      structures of the toxin in solution with the X-ray crystal structure of its
      homologous protein, cardiotoxin V4II from Naja mossambica mossambica, showed good
      agreement between the structures except at segments of the turns. As the
      functions of short neurotoxins and cardiotoxins are distinct, despite their
      similar secondary structural patterns and tertiary folding, a comparative
      analysis has been carried out between cardiotoxin III and short neurotoxins of
      known structures. We discuss their structural features in order to clarify
      relationships between their structure and function.

PMID- 8308892
TI  - Solution structure of a pair of fibronectin type 1 modules with fibrin binding
      activity.
AB  - The tertiary structure of the fourth and fifth type 1 module pair from the N
      terminus of human fibronectin, has been determined by two-dimensional homonuclear
      1H nuclear magnetic resonance (NMR) spectroscopy. Comparison of each module fold
      with those of two other type 1 modules shows that the type 1 "consensus"
      structure is conserved in the pair. The modules connect end-to-end to form an
      elongated structure with a limited clockwise twist around the long axis, from N
      to C terminus. The short five residue linker sequence forms a tight loop and the
      relative orientation of the two modules is maintained by fixed and intimate
      hydrophobic contacts, dominated by a non-conserved tryptophan residue from the
      fourth type 1 module. The protein binds specifically to fibrin in an ELISA and
      surface accessible residues that may be involved in this and other protein
      interactions can be identified. The structure provides an insight into how chains
      of type 1 modules may link up in intact fibronectin.

PMID- 8308893
TI  - Formation of alpha-helix 88-98 is essential in the establishment of higher-order
      structure from reduced lysozyme.
AB  - Lys96 and Lys97 in lysozyme are located at the C terminus of alpha-helix 88-98.
      The positive charges of these residues are supposed to stabilize the helical
      structure, and these residues are conserved as the basic amino acids among c-type
      lysozymes. The renaturation rate of reduced mutant lysozyme, where both Lys96 and
      Lys97 were mutated together to Ala, was slower than that of native lysozyme at pH
      8.0 and 37 degrees C by SH-SS interchange reactions. In order to investigate the
      reason, the peptide fragment 36-105 (where we can obtain information of the
      interaction between helix 88-98 and Trp62 and Trp63 residues) was prepared. CD
      spectra were compared between peptide fragment 36-105 and its acetylated form,
      where the positive charges of Lys96 and Lys97 were eliminated, and it was
      elucidated that the displacement of positive charges at the C terminus of the
      helix caused the shift of the advantageous structure of the fragment from alpha
      helix to coil. Moreover, we obtained evidence that there was interaction of the
      helix with Trp62 and/or Trp63, which maintained a thermodynamically stable higher
      order structure. Therefore, these results suggest that the formation of alpha
      helical structure in 88-98 is a significant factor in the establishment of native
      structure from reduced lysozyme.

PMID- 8308894
TI  - Thermodynamic puzzle of apomyoglobin unfolding.
AB  - It has been shown that a compact, partly unfolded state of apomyoglobin, which is
      obtained in acidic solutions, had a heat capacity lower than that of the unfolded
      polypeptide chain. With increasing temperature, this intermediate state unfolds
      in a rather narrow temperature region. Its unfolding is accompanied by an
      increase of the heat capacity, which reaches the value specific for the fully
      unfolded polypeptide chain having all groups exposed to water. This unfolding,
      however, proceeds without the excess heat absorption expected for a temperature
      induced two-state transition. This eliminates the possibility of considering this
      process as a first order phase transition, as gross conformational transitions in
      proteins are usually considered. It appears that the process of unfolding of the
      intermediate state of apomyoglobin might represent a second order phase
      transition, which has been predicted on theoretical grounds for those compact
      proteins without unique structure, known as "molten globules".

PMID- 8308895
TI  - Mutation of tyrosine-67 to phenylalanine in cytochrome c significantly alters the
      local heme environment.
AB  - The high resolution three-dimensional atomic structures of the reduced and
      oxidized states of the Y67F variant of yeast iso-1-cytochrome c have been
      completed. The conformational differences observed are localized directly in the
      mutation site and in the region about the pyrrole A propionate. Shifts in atomic
      positions are largely restricted to nearby amino acid side-chains, whereas little
      perturbation of the polypeptide chain backbone is observed. One prominent
      difference between the variant and wild-type structures involves a substantial
      increase in the size of an already existing internal cavity adjacent to residue
      67. This same cavity contains an internally bound water molecule (Wat166), which
      is found in all eukaryotic cytochromes c for which structures are available. In
      the reduced Y67F mutant protein a second water molecule (Wat300) is observed to
      reside in this enlarged internal cavity, assuming a position approximately
      equivalent to that of the hydroxyl group of Tyr67 in the wild-type protein. A
      further consequence of this mutation is the alteration of the hydrogen bond
      network between Tyr67, Wat166 and other nearby residues. This appears to be
      responsible for the absence of oxidation state dependent changes in polypeptide
      chain flexibility observed in the wild-type protein. Furthermore, loss of the
      normally resident Tyr67 OH to Met80 SD hydrogen bond leads to a significantly
      lower midpoint reduction potential. These results reaffirm proposals that both
      Tyr67 and Wat166 play a central role in stabilizing the alternative oxidation
      states of cytochrome c.

PMID- 8308896
TI  - Crystallization of 31 kDa C-terminal fragment of rat DNA polymerase beta.
AB  - A 248 residue C-terminal fragment of rat DNA polymerase beta (335 amino acid
      residues), a eukaryotic DNA repair enzyme, has been crystallized from
      polyethylene glycol 6000 solution. The crystals are orthorhombic, space group
      P2(1)2(1)2 with cell dimensions a = 120.3 A, b = 64.2 A, c = 39.4 A, and contain
      a single 31 kDa fragment in an asymmetric unit. The crystals diffract to 2.8 A
      resolution with laboratory X-ray source, and to 2.3 A resolution with synchrotron
      X-ray source, and are suitable for detailed structural analysis.

PMID- 8308897
TI  - Crystallization, characterization and preliminary crystallographic studies of
      carbamate kinase of Streptococcus faecium.
AB  - Crystals of carbamate kinase (E.C.2.7.2.2) suitable for high resolution studies
      have been obtained, using the hanging drop vapour diffusion technique, with
      polyethylene glycol 8000 and NaCl as precipitants at pH 6.5 and a temperature of
      4 degrees C. Crystals of about 0.3 mm x 0.2 mm x 0.2 mm in size diffract to at
      least 3.2 A resolution and are stable to X-radiation for more than ten hours. The
      space group is P2(1)2(1)2(1), with unit cell dimensions a = 84.5 A, b = 99.6 A, c
      = 173.3 A. Density packing considerations are consistent with the presence of
      four to five monomers (M(r) of the monomer = 33,000) in the asymmetric unit, two
      dimers or even a tetramer being favoured by the results of cross-linking
      experiments of the enzyme in solution.

PMID- 8308898
TI  - Crystallization and preliminary diffraction analysis of the catalytic domain of
      xylanase Z from Clostridium thermocellum.
AB  - The catalytic domain of a thermostable xylanase from Clostridium thermocellum has
      been expressed in Escherichia coli and crystallized from a polyethylene glycol
      2000 solution by the hanging drop method. Crystals belong to the triclinic space
      group P1 with cell dimensions a = 46.8 A, b = 50.8 A, c = 70.3 A, alpha = 100.7
      degrees, beta = 83.8 degrees, gamma = 101.6 degrees, and two molecules in the
      unit cell. These crystals diffract X-rays to at least 1.8 A resolution and are
      suitable for high-resolution X-ray analysis.

PMID- 8308899
TI  - Identification of a divergent actin-related protein in Drosophila.
AB  - The actin-related proteins (ARPs) have primary sequence homology to actin, have
      no homology to other proteins and, unlike the conventional actins, are clearly
      divergent. We have identified an ARP in Drosophila that has approximately 30%
      amino acid identity to most actins, making it the most divergent yet reported. It
      is also quite divergent from all other ARP sequences. When the Drosophila ARP is
      aligned with actin it contains sequence insertions, as is the case with all other
      ARPs. The unique location of the insertions, as well as its overall divergence,
      indicates it may represent a new isotype. Only one gene was detected by
      hybridization to both genomic DNA and polytene chromosomes; the location of the
      gene is 13E on the X chromosome. A transcript of 1350 bases was detected at all
      stages of development. This transcript was relatively abundant during early
      embryogenesis, decreasing during the later stages of embryogenesis and increasing
      again in larvae and adults.

PMID- 8308900
TI  - Arabidopsis thaliana NAPHP thioredoxin reductase. cDNA characterization and
      expression of the recombinant protein in Escherichia coli.
AB  - Using a clone characterized in the course of a random sequencing programme of
      Arabidopsis thaliana, two cDNAs encoding plant type cytosolic NADPH-dependent
      thioredoxin reductase (NTR) have been isolated. Their sequence homology with
      Escherichia coli NRT (the only thioredoxin reductase of known primary structure)
      is about 45%. In addition, analysis of the sequence of the encoded polypeptide
      (333 amino acids) reveals that several motifs are conserved in the FAD, central
      and NADPH binding domains, suggesting a similar folding of the protein.
      Definitive proof that the clone ATTHIREDB indeed encodes NTR was obtained by
      expressing the recombinant protein in E. coli cells. It was observed that plant
      type NTR was strongly overproduced (about 10 mg homogeneous protein could be
      purified per liter of culture). The recombinant enzyme is homodimeric, each
      subunit containing an FAD prosthetic group. Recombinant plant type NTR is as
      effective as E. coli NTR in the DTNB (5,5'-dithiobis nitrobenzoic acid) reduction
      reaction, but its affinity for thioredoxin substrates was strikingly different.
      These results are discussed in relation to the primary structures of NADPH
      thioredoxin reductases.

PMID- 8308901
TI  - Comparison between the complete mtDNA sequences of the blue and the fin whale,
      two species that can hybridize in nature.
AB  - The sequence of the mitochondrial DNA (mtDNA) molecule of the blue whale
      (Balaenoptera musculus) was determined. The molecule is 16,402 bp long and its
      organization conforms with that of other eutherian mammals. The molecule was
      compared with the mtDNA of the congeneric fin whale (B. physalus). It was
      recently documented that the two species can hybridize and that male offspring
      are infertile whereas female offspring may be fertile. The present comparison
      made it possible to determine the degree of mtDNA difference that occurs between
      two species that are not completely separated by hybridization incompatibility.
      The difference between the complete mtDNA sequences was 7.4%. Lengths of peptide
      coding genes were the same in both species. Except for a small portion of the
      control region, disruption in alignment was usually limited to insertion/deletion
      of a single nucleotide. Nucleotide differences between peptide coding genes
      ranged from 7.1 to 10.5%, and difference at the inferred amino acid level was 0.0
      7.9%. In the rRNA genes the mean transition difference was 3.8%. This figure is
      similar in degree to the difference (3.4%) between the 12S rRNA gene of humans
      and the chimpanzee. The mtDNA differences between the two whale species,
      involving both peptide coding and rRNA genes, suggest an evolutionary separation
      of > or = 5 million years. Although hybridization between more distantly related
      mammalian species may not be excluded, it is probable that the blue and fin
      whales are nearly as different in their mtDNA sequences as hybridizing mammal
      species may be.

PMID- 8308902
TI  - The nucleotide sequence of the mitochondrial DNA molecule of the grey seal,
      Halichoerus grypus, and a comparison with mitochondrial sequences of other true
      seals.
AB  - The sequence of the mtDNA of the grey seal, Halichoerus grypus, was determined.
      The length of the molecule was 16,797 base pairs. The organization of the
      molecule conformed with that of other eutherian mammals but the control region
      was unusually long due to the presence of two types of repeated motifs. The grey
      seal and the previously reported harbor seal, Phoca vitulina, belong to different
      but closely related genera of family Phocidae, true (or earless) seals. In order
      to determine the degree of differences that may occur between mtDNAs of closely
      related mammalian genera, the 2 rRNA genes, the 13 peptide coding genes, and the
      22 tRNA genes of the 2 species were compared. Total nucleotide difference in the
      peptide coding genes was 2.0-6.1%. The range of conservative difference was 0.0
      1.5%. In the inferred peptide sequences the amino acid difference was 0.0-4.5%,
      and the difference with respect to chemical properties of amino acids was 0.0
      3.0%. A gene that showed a limited degree of difference in one mode of comparison
      did not necessarily show a corresponding limited difference in another mode. The
      ratio for differences in codon positions 1, 2, and 3 was approximately 2.7:1:16.
      The corresponding ratio for conservative differences was approximately 1.8:1.1:1.
      The evolutionary separation of the two species was calculated to have taken place
      2-2.5 million years ago. This dating gives the figure approximately 8 x 10(-9) as
      the mean rate of substitution per site and year in the entire mtDNA molecule.
      Comparison with the cytochrome b gene of the Hawaiian monk seal and the Weddell
      seal suggested that the lineage of these two species and that of the grey and
      harbor seals separated approximately 8 million years ago.

PMID- 8308903
TI  - Genome organization and species formation in vertebrates.
AB  - Some years ago Wilson and co-workers proposed that the higher rates of karyotypic
      change and species formation of mammals compared to cold-blooded vertebrates are
      due to the formation of small demes, as favored by the social structuring and
      brain development of the former. Here, evidence is reviewed which indicates that
      mammals are more prone to karyotypic change and species formation than cold
      blooded vertebrates because of their different genome organization. Similar
      evidence has also recently become available for birds. While this different
      organization appears to be a necessary and, in all likelihood, a sufficient
      condition for the increased rates of karyotypic change and species formation
      found in mammals, it is still possible that social structuring and brain
      development may have played an additional accelerating role.

PMID- 8308904
TI  - Toward a more accurate time scale for the human mitochondrial DNA tree.
AB  - Several estimates of the time of occurrence of the most recent common
      mitochondrial DNA (mtDNA) ancestor of modern humans have been made. Estimates
      derived from noncoding regions based on a model that classifies sites into two
      categories (variable and invariable) have been consistently older than those
      derived from the third positions of codons. This discrepancy can be attributed to
      a violation of the assumption of rate homogeneity among variable sites when
      analyzing the noncoding regions. Additional data from the partial control region
      sequences allow us to take into account some of this further heterogeneity. By
      assigning the sites to three classes (highly variable, moderately variable, and
      invariable) and by assuming that the last common mtDNA ancestor of humans and
      chimpanzees lived 4 million years ago, the most recent common mtDNA ancestor of
      humans is estimated to have occurred 211,000 +/- 111,000 years ago (+/- 1 SE),
      consistent with the estimate, 101,000 +/- 52,000 years, made from third positions
      of codons and also with those proposed previously. We used the same technique to
      estimate when a putative expansion of modern humans out of Africa took place and
      estimated a time of 89,000 +/- 69,000 years ago. Even though the standard errors
      of these estimates are large, they allow us to reject the multiregional
      hypothesis of modern human origin.

PMID- 8308905
TI  - Characterization of the cow stomach lysozyme genes: repetitive DNA and concerted
      evolution.
AB  - Cow stomach lysozyme genes have evolved in a mosaic pattern. The majority of the
      intronic and flanking sequences show an amount of sequence difference consistent
      with divergent evolution since duplication of the genes 40-50 million years ago.
      In contrast, exons 1, 2, and 4 and immediately adjacent intronic sequences differ
      little between genes and show evidence of recent concerted evolution. Exon 3
      appears to be evolving divergently. The three characterized genes vary from 5.6
      to 7.9 kilobases in length. Different distributions of repetitive DNA are found
      in each gene, which accounts for the majority of length differences between
      genes. The different distributions of repetitive DNA in each gene suggest the
      repetitive elements were inserted into each gene after the duplications that give
      rise to these three genes and provide additional support for divergent evolution
      for the majority of each gene. The observation that intronic and flanking
      sequences are evolving divergently suggests that the concerted evolution events
      involved in homogenizing the coding regions of lysozyme genes involve only one
      exon at a time. This model of concerted evolution would allow the shuffling of
      exon-sized pieces of information between genes, a phenomenon that may have aided
      in the early adaptive evolution of stomach lysozyme.

PMID- 8308906
TI  - Pathways of lysozyme evolution inferred from the sequences of cytochrome b in
      birds.
AB  - A reliable phylogeny relating the major groups of Galliformes was sought in order
      to shed light on an unusual case of coupled amino acid replacements in the
      lysozymes c of these birds. The New World quail and the African guinea fowl share
      a unique trio of amino acids at three internal positions but have been separated
      phylogenetically by the majority of trees based on morphological characters.
      Alternative hypotheses based on molecular data have suggested an arrangement that
      would be more parsimonious with regard to the lysozyme data. The entire
      mitochondrial cytochrome b gene (1,143 bp) was amplified via the polymerase chain
      reaction (PCR) and sequenced for nine galliforms and a representative anseriform
      to provide DNA sequence data for a phylogenetic reconstruction. The mode and
      tempo of change in these sequences were analyzed to determine the characters most
      appropriate for phylogenetic reconstruction. Our results place the New World
      quail outside all other representative game birds except the cracids. Although in
      conflict with various morphological analyses, this finding is consistent with the
      results of DNA-DNA hybridization studies. A model to account for the coupled
      replacements in the lysozymes is presented. Our results also suggest a rapid but
      ancient radiation among the Galliformes such that the majority of cytochrome b
      sequence differences among taxa have accumulated on the terminal branches of the
      reconstructed phylogenetic trees.

PMID- 8308907
TI  - Evolution of the recA gene and the molecular phylogeny of bacteria.
AB  - The DNA sequences of the recA gene from 25 strains of bacteria are known. The
      evolution of these recA gene sequences, and of the derived RecA protein
      sequences, is examined, with special reference to the effect of variations in
      genomic G + C content. From the aligned RecA protein sequences, phylogenetic
      trees have been drawn using both distance matrix and maximum parsimony methods.
      There is a broad concordance between these trees and those derived from other
      data (largely 16S ribosomal RNA sequences). There is a fair degree of certainty
      in the relationships among the "Purple" or Proteobacteria, but the branching
      pattern between higher taxa within the eubacteria cannot be reliably resolved
      with these data.

PMID- 8308908
TI  - The sequence-immunology correlation revisited: data for cetacean myoglobins and
      mammalian lysozymes.
AB  - Quantitative microcomplement fixation tests employing rabbit antisera were done
      to compare immunologically 13 cetacean myoglobins and 15 mammalian lysozymes c of
      known amino acid sequence. In both cases there was a strong correlation between
      immunological distance (y) and percent sequence difference (x), as had been found
      for several other globular proteins. For myoglobin the relationship could be
      described by y = 10.5x and for lysozyme by y = 8.5x. The coefficients in both of
      these equations are appreciably higher than the values of 5.1-6.9 reported for
      three other vertebrate globular proteins (bird lysozyme c, mammalian
      ribonuclease, and mammalian serum albumin), and they imply that rabbit antisera
      to mammalian myoglobins and lysozymes are more sensitive to evolutionary
      substitutions. A strong inverse correlation (r = -0.95) was found when the slope
      of the line relating y to x for these five data sets was plotted against the
      percent sequence difference between the rabbit's own protein and the proteins
      immunized with. Specifically, the cetacean myoglobins on average differ in amino
      acid sequence from rabbit myoglobin by less than 13% and exhibit the steepest
      slope (10.5), while bird lysozyme sequences differ by nearly 40% from rabbit
      lysozyme and exhibit the shallowest slope (5.1).

PMID- 8308909
TI  - Sequence evolution in and around the mitochondrial control region in birds.
AB  - By cloning and sequencing 3.4 kilobases of snow goose mtDNA we found that the ND5
      gene is followed by the genes for cytochrome b, tRNA(Thr), tRNA(Pro), ND6,
      tRNA(Glu), the control region, tRNA(Phe), and srRNA. This order is identical to
      that of chicken, quail, and duck mtDNA but differs from that of mammals and a
      frog (Xenopus). The mean extent of difference due to base substitution between
      goose and chicken is generally closer to the same comparison between rat and
      mouse but less than that between human and cow. For one of the nine regions
      compared (tRNA(Glu)), the bird differences appear to be anomalous, possibly
      implicating altered functional constraints. Within the control region, several
      short sequences common to mammals are also conserved in the birds. Comparison of
      the goose control region with that of quail and chicken suggests that a sequence
      element with similarity to CSB-1 duplicated once prior to the divergence of goose
      and chicken and again on the lineage leading to chicken. Between goose (or duck)
      and chicken there are four times more transversions at the third positions of
      fourfold-degenerate codons in mitochondrial than in nuclear genes.

PMID- 8308910
TI  - Evolution of protamine P1 genes in primates.
AB  - Protamine P1 genes have been sequenced by PCR amplification and direct DNA
      sequencing from 9 primates representing 5 major families, Cebidae (new world
      monkeys), Cercopithecidae (old world monkeys), Hylobatidae (gibbons), Pongidae
      (gorilla, orangutan, and chimpanzee), and Hominidae (human). In this recently
      diverged group of primates these genes are clearly orthologous but very variable,
      both at the DNA level and in their expressed amino acid sequences. The rate of
      variation amongst the protamine P1s indicates that they are amongst the most
      rapidly diverging polypeptides studied. However, some regions are conserved both
      in primates and generally in other placental mammals. These are the 13 N-terminal
      residues (including a region of alternating serine and arginine residues (the
      motif SRSR, res. 10-13) susceptible to Ser phosphorylation), a tract of six Arg
      residues (res. 24-29) in the center of the molecule, and a six-residue region
      (RCCRRR, res. 39-44), consisting of a pair of cysteines flanked by arginines.
      Detailed consideration of nearest-neighbor matrices and trees based on maximum
      parsimony indicates that P1 genes from humans, gorillas, and chimpanzees are very
      similar. The amino acid and nucleotide differences between humans and gorillas
      are fewer than those between humans and chimpanzees. This finding is at variance
      with data from DNA-DNA hybridization and extensive globin and mitochondrial DNA
      sequences which place human and chimpanzee as closest relatives in the super
      family, Hominoidea. This may be related to the fact that protamine P1s are
      expressed in germ line rather than somatic cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8308911
TI  - The differences among Jewish communities--maternal and paternal contributions.
AB  - The haplotypes of Y chromosome (paternally inherited) and mtDNA (maternally
      inherited) were analyzed in representatives of six Jewish communities
      (Ashkenazic, North African, Near Eastern, Yemenite, Minor Asian/Balkanian, and
      Ethiopian). For both elements, the Ethiopian community has a mixture of typically
      African and typically Caucasian haplotypes and is significantly different from
      all others. The other communities, whose haplotypes are mostly Caucasian, are
      more closely related; significant differences that were found among some of them
      possibly indicate the effects of admixture with neighboring communities of non
      Jews. The different contribution of the Y chromosome and mtDNA haplotypes to the
      significant differences among the communities can be explained by unequal
      involvement of males and females in the different admixtures. In all communities,
      except the Ethiopians, the level of diversity (h) for Y chromosome haplotypes is
      higher than that for mtDNA haplotypes, suggesting that in each community the
      people who become parents include more males than females. An opposite proportion
      (more females than males) is found among the Ethiopians.

PMID- 8308913
TI  - The paradoxical nature of sexuality in anorexia nervosa.
AB  - Psychosexual dysfunctioning is often put forward as an etiological factor in
      anorexia nervosa. In contrast, we hypothesize that anorexia nervosa patients were
      in general psychosexually normal before their illness, and that the problems in
      their sexual life arise only after the emergence of hypogonadism, as a
      consequence of emaciation. Our study shows that patients, before they became
      anorectic, were indeed rather similar to normal subjects with respect to sexual
      attitude. Moreover, patients reported a considerably decreased sexual interest
      during their anorectic period when compared with normal controls. We conclude
      that these results corroborate our hypotheses. In the discussion we sketch a
      theoretical account of the origin and course of anorexia nervosa, according to
      which the hormonal and associated psychosexual changes are central to its
      pathogenesis.

PMID- 8308912
TI  - Mammalian gene evolution: nucleotide sequence divergence between mouse and rat.
AB  - As a paradigm of mammalian gene evolution, the nature and extent of DNA sequence
      divergence between homologous protein-coding genes from mouse and rat have been
      investigated. The data set examined includes 363 genes totalling 411 kilobases,
      making this by far the largest comparison conducted between a single pair of
      species. Mouse and rat genes are on average 93.4% identical in nucleotide
      sequence and 93.9% identical in amino acid sequence. Individual genes vary
      substantially in the extent of nonsynonymous nucleotide substitution, as expected
      from protein evolution studies; here the variation is characterized. The extent
      of synonymous (or silent) substitution also varies considerably among genes,
      though the coefficient of variation is about four times smaller than for
      nonsynonymous substitutions. A small number of genes mapped to the X-chromosome
      have a slower rate of molecular evolution than average, as predicted if molecular
      evolution is "male-driven." Base composition at silent sites varies from 33% to
      95% G+C in different genes; mouse and rat homologues differ on average by only
      1.7% in silent-site G+C, but it is shown that this is not necessarily due to any
      selective constraint on their base composition. Synonymous substitution rates and
      silent site base composition appear to be related (genes at intermediate G+C have
      on average higher rates), but the relationship is not as strong as in our earlier
      analyses. Rates of synonymous and nonsynonymous substitution are correlated,
      apparently because of an excess of substitutions involving adjacent pairs of
      nucleotides. Several factors suggest that synonymous codon usage in rodent genes
      is not subject to selection.

PMID- 8308914
TI  - Some clinical and psychometric characteristics of primary and secondary premature
      ejaculators.
AB  - Patients with premature ejaculation (PE) were subdivided into primary (PPE),
      individuals who had suffered from PE since the beginning of their sexual lives,
      and secondary (SPE), those who developed the condition after years of
      satisfactory sexual functioning. PPEs differed from SPEs on a number of clinical
      and psychometric variables. Clinically SPEs were significantly more likely to
      manifest a coexisting erectile disorder, reduction in sex drive, and a decrease
      in arousal during sexual stimulation than SPEs. They were significantly less
      likely to report high levels of anxiety during coitus. Psychometrically, on the
      Derogatis Sexual Functioning Inventory, PPEs were significantly more "impaired"
      than the SPEs as reflected by scores on the Symptoms and Satisfaction scales and
      the GSSI. They were significantly less impaired on measures of sex drive (e.g.,
      Drive and Fantasy). On the Hamilton Anxiety Rating Scale (HRAS), the PPEs scored
      as significantly more anxious than the SPEs. The findings suggest that
      dichotomizing PE into PPE and SPE may be clinically useful, and may have
      etiologic treatment and prognostic implications.

PMID- 8308915
TI  - Masturbatory guilt and sexual responsiveness among post-college-age women: sexual
      satisfaction revisited.
AB  - Although masturbation has come to be viewed as an appropriate sexual outlet for
      women, it is the one form of sexual behavior that has been most harshly treated
      throughout the centuries by society, religion, and the field of medicine. Thus,
      despite the increased incidence of masturbation among adult women during the
      1970s and 1980s, substantial evidence suggests that guilt feelings associated
      with the practice may interfere with physiological and psychological sexual
      satisfaction in general. The purposes of this study were to determine the degree
      of masturbatory guilt, if any, and its effects on the sexual responsiveness and
      sexual satisfaction of adult women. An anonymous questionnaire concerning self
      perception of the female sexual response was administered to female, registered
      nurses in 15 states, yielding a sample of 868 respondents. The 671 respondents
      who were the focus of this investigation had engaged in masturbation and revealed
      their guilt status regarding the practice. Those women who reported guilt
      feelings associated with masturbation were more likely to have negative feelings
      toward the practice and less likely to indicate positive physiological and
      psychological reactions after engaging in self-stimulation. Further, they were
      less likely to report sexual adjustment, physiological sexual satisfaction, and
      psychological sexual satisfaction. Since masturbation has emerged as a potential
      sexual outlet and as a means to engage in personal body exploration for women,
      these findings have substantial implications for therapists, physicians,
      sexuality professionals, and researchers.

PMID- 8308916
TI  - Partial versus complete autogynephilia and gender dysphoria.
AB  - Autogynephilia (sexual arousal in men produced by the thought or image of
      themselves as women) is often associated with gender dysphoria (the desire to
      belong to the opposite sex). Previous research has shown that autogynephiles who
      are principally aroused by images of themselves as nude women are more gender
      dysphoric than those principally aroused by images of themselves as partially or
      fully dressed women. This study tested the hypothesis that the feature of the
      nude self-image most responsible for its correlation with gender dysphoria is the
      imagined vulva. The subjects were 220 nonhomosexual male outpatients who reported
      sexual arousal while imagining themselves with one or more features of the female
      anatomy. Autogynephilia and gender dysphoria were assessed with questionnaires.
      The findings confirmed that men who are sexually aroused at the thought of having
      a vulva are more likely to want to be women.

PMID- 8308917
TI  - Fantasy and reality: an essay on incest.
AB  - The question of fantasy and reality in incest cases has been and continues to be
      a complex and much debated issue. From an historical perspective this issue was
      at its peak following Freud's introduction of the seduction theory. The
      renunciation of his theory and the silence that ensued for decades placed this
      debate on hold. Now that incest is again being acknowledged, clinicians are once
      again confronted with the issue of reality versus fantasy. This paper will
      demonstrate different ways the relationship between fantasy and reality in
      incestuous experiences may be expressed. The need to reexamine our positions and
      to bring the interplay of fantasy and reality back to the forefront will be
      addressed.

PMID- 8308918
TI  - Female sexuality: a comparative study between women in homosexual and
      heterosexual relationships.
AB  - To explore female sexuality, a student population of women (ages 23-35 years) in
      intimate relationships were stratified and matched for demographics into two
      samples, homosexual and heterosexual, each group consisting of 34 women.
      Significant differences emerged between the two groups on seven of the nine
      variables. The homosexual women in this study demonstrated greater interpersonal
      dependency, compatibility, and intimacy in their intimate relationships. The
      heterosexual women evidenced more positive dispositions toward sexual fantasy,
      greater sexual assertiveness, stronger sexual desire, and higher frequencies of
      sexual activity. Despite these findings, there were no significant differences
      between the two groups in sexual satisfaction.

PMID- 8308919
TI  - Germline p53 gene mutations and cancer--Pandora's box or open sesame?

PMID- 8308920
TI  - Time of truth for cancer vaccines.

PMID- 8308921
TI  - Gene therapy trial for lung cancer: caught between the RAC and a hard place.

PMID- 8308922
TI  - Guidelines recommended for sponsored research agreements.

PMID- 8308923
TI  - Cover costs, test treatments, pay patients: health care reform hearings hot on
      Hill.

PMID- 8308924
TI  - Congress maintains interest in NIH matters.

PMID- 8308925
TI  - Postvaccinal sarcomas in cats.

PMID- 8308926
TI  - Germline p53 gene mutations in subsets of glioma patients.
AB  - BACKGROUND: Heritable germline mutations of the p53 gene have been described in
      patients with Li-Fraumeni syndrome, occasionally in nonfamilial malignancies such
      as multifocal osteosarcoma, in a small subgroup of young patients with two or
      more primary malignancies, and in patients with sporadic breast carcinoma. We
      recently reported that multifocal gliomas are frequently associated with other
      primary malignancies, and we hypothesized that genetic alterations may account
      for this phenomenon. PURPOSE: We examined the frequency of germline p53 gene
      mutations in patients with glioma and either multifocality of lesions, history of
      an additional primary (different) malignancy, or a family history of cancer.
      METHODS: Lymphocytes from 51 glioma patients were analyzed for germline p53 gene
      mutations using RNA-polymerase chain reaction analysis, single-strand
      conformation polymorphism, and gene sequencing techniques. RESULTS: Germline p53
      gene mutations were detected in six of 19 patients with multifocal glioma,
      including two with family history of cancer, one with another primary malignancy,
      and two with all three risk factors; one of four patients with unifocal glioma,
      another primary malignancy, and a family history of cancer; and two of 15
      patients with unifocal glioma and a family history of cancer but no second
      malignancies. No mutations were detected in the patient with unifocal glioma and
      another malignancy or in the 12 control patients with unifocal glioma and no
      second malignancies or family history of cancer. Patients having mutations were
      younger than other patients in the same group. CONCLUSIONS: Germline p53
      mutations are frequent in patients with multifocal glioma, glioma and another
      primary malignancy, and glioma associated with a family history of cancer,
      particularly if these factors are combined. IMPLICATIONS: Relatives at high risk
      can be identified for genetic counseling, early cancer detection, and possible
      enrollment in chemoprevention trials.

PMID- 8308927
TI  - Clinical relevance of the i(12p) marker chromosome in germ cell tumors.
AB  - BACKGROUND: Germ cell tumors in men are curable at all stages and are among the
      most sensitive of all cancers to chemotherapy. An isochromosome of the short arm
      of chromosome 12, i(12p), has been reported to be a frequent marker of these
      tumors and to have diagnostic and prognostic significance. PURPOSE: We evaluated
      the possible association between this cytogenetic marker and clinical outcome for
      men with germ cell tumors. METHODS: One hundred seventy-eight germ cell tumor
      samples from 150 men were studied using conventional and molecular cytogenetic
      techniques. Of these samples, 171 were evaluable. Patient characteristics,
      disease stage, treatment outcome, and disease status were correlated with the
      observed cytogenetic changes. In addition, 28 biopsy specimens obtained from 28
      patients with tumors of uncertain histogenesis were evaluated to determine
      whether the presence of i(12p) could serve as a diagnostic marker of a germ cell
      origin for these tumors. RESULTS: Of the 171 evaluable tumor accessions, 101
      (59%) yielded abnormal karyotypes. i(12p) was determined to be present in 79 of
      the 101 (79%) abnormal karyotypes, which were derived from all cell types and
      primary sites. An abnormal karyotype was more frequently obtained from
      nonseminomatous tumors (91/137 [81%]) than from seminomas (10/34 [30%] [P <
      .001]). Tumors resulting in a cytogenetic failure were more likely to respond
      completely to chemotherapy than tumors with an abnormal karyotype (P = .004).
      i(12)p copy number was not associated with response or survival. Fluorescence in
      situ hybridization using a chromosome 12 centromere-specific probe detected
      i(12p) in 47 of 47 tumors (100%) already shown to have i(12p) by cytogenetic
      analysis and in 13 of 49 tumors (27%) exhibiting either an abnormal karyotype or
      a cytogenetic failure. One or more copies of i(12p), excess 12p copy number, or a
      deletion on the long arm of chromosome 12 was found in seven of 28 (25%) midline
      tumors of uncertain histogenesis, thus establishing a diagnosis of a germ cell
      tumor in these patients. One partial and five complete responses were observed in
      these seven patients. Only two partial responses were seen in the 17 patients who
      had no detectable germ cell tumor-related cytogenetic marker (P = .009).
      CONCLUSIONS: i(12p) is a highly nonrandom chromosomal marker seen in about 80% of
      male germ cell tumors with evaluable cytogenetic abnormalities. The presence of
      this isochromosome has diagnostic and possibly prognostic importance for patients
      with these tumors. IMPLICATIONS: Cytogenetic studies of germ cell tumors in
      prospective clinical treatment trials are warranted to define more precisely the
      relationship between histologic subtype, serum tumor marker production, and
      prognosis.

PMID- 8308928
TI  - Benign-to-malignant B16 melanoma progression induced in two stages in vitro by
      exposure to hypoxia.
AB  - BACKGROUND: Benign tumors apparently become malignant by generating a succession
      of variants with ever-greater growth potential and autonomy. Such stepwise
      progression has not been achieved in vitro under conditions likely to occur in
      developing tumors. PURPOSE: Tumors initiated by clone G3.5 of the mouse B16
      melanoma regularly generate stable variants that are more malignant. We
      investigated the possibility that hypoxia might promote stepwise progression
      along a benign-to-malignant pathway in monolayer cultures of G3.5 cells. METHODS:
      Confluent monolayers of metastatic clone G3.5 and the nonmetastatic clone G3.15
      were subjected to severe hypoxia (< 50 ppm O2) for up to 72 hours, or to moderate
      hypoxia (300-1200 ppm O2) for up to 12 days, and were then maintained
      subconfluent or at confluence for several weeks to permit emergence of
      progression variants. The relative malignancy of variants was assayed in vivo
      after subcutaneous injection into mice, by measuring tumor growth rate and
      counting lung metastases, and after intravenous injection, by counting lung
      colonies. In vitro assessment of the variants involved growth as monolayers with
      or without serum, growth in soft agar, and measurement of invasiveness. RESULTS:
      G3.5 cells were converted to a more malignant variant (G3.5*) by 12-48 hours of
      severe hypoxia, or longer periods of moderate hypoxia, when followed by
      maintenance at confluence for 3-5 weeks. Conversions occurred in discrete foci of
      morphologically-discernible cells (optimum focus formation about one in 1-2 x
      10(5) cells) that rapidly expanded to dominate the cultures. The G3.5* phenotype
      was comparable to the conversion phenotype generated in tumors and included
      acquisition of growth autonomy in serum-free medium. G3.15 cells were converted
      to a G3.5-like phenotype by one round of exposure to hypoxia and confluence, and
      then to the G3.5* phenotype during a second round, at a low frequency (one focus
      in 5 x 10(6) cells). This behavior was consistent with a failure of all but the
      largest G3.15 tumors to generate G3.5* conversion cells. CONCLUSIONS: Progression
      from a relatively benign phenotype, G3.15, to a highly malignant phenotype,
      G3.5*, can be produced in monolayer culture in two stable stages by sequential
      rounds of exposure to hypoxia and confluence. The resulting conversions
      corresponded to phenotypes generated within tumors. Both conversions resulted in
      populations with enhanced growth capabilities, which could establish dominance
      within tumors. IMPLICATIONS: The stepwise conversion of B16 melanoma clones
      provides a unique model for the in vitro investigation of mechanisms underlying
      acquisition of malignancy during tumor development.

PMID- 8308929
TI  - Phase I study of adozelesin administered by 24-hour continuous intravenous
      infusion.
AB  - BACKGROUND: Adozelesin, a synthetic analogue of the antitumor antibiotic CC-1065,
      is the first of a class of potent sequence-specific alkylating agents to be
      brought to clinical trial. In preclinical in vitro testing, it has demonstrated
      antitumor activity at picomolar concentrations. PURPOSE: We conducted a phase I
      study of adozelesin to (a) determine a recommended dose for phase II testing
      using a 24-hour intravenous infusion, (b) characterize the toxic effects of the
      drug using this schedule, and (c) document any antitumor activity observed.
      METHODS: Adozelesin was given as a 24-hour continuous intravenous infusion.
      Treatments were initially scheduled every 3 weeks, but the prolonged
      myelosuppression observed necessitated a final dosing interval of every 6 weeks.
      The starting dose of 30 micrograms/m2 was escalated using a modified Fibonacci
      scheme until dose-limiting toxicity was encountered. RESULTS: Twenty-nine
      patients were entered in the study. Successive dose levels used were 30, 60, 100,
      150, 120, and 100 micrograms/m2. Prolonged thrombocytopenia and granulocytopenia
      were dose limiting. No antitumor responses were observed. CONCLUSION: We
      recommend that the phase II dose of adozelesin given as a continuous 24-hour
      intravenous infusion be 100 micrograms/m2, repeated every 6 weeks. Other
      potentially less myelosuppressive schedules could be pursued.

PMID- 8308930
TI  - Mortality patterns among chemical plant workers exposed to formaldehyde and other
      substances.

PMID- 8308931
TI  - Epidemiologic evidence showing that human papillomavirus infection causes most
      cervical intraepithelial neoplasia.

PMID- 8308932
TI  - Radiation-induced breast cancer: long-term follow-up of radiation therapy for
      benign breast disease.

PMID- 8308933
TI  - Psychotherapy with dual diagnosis patients: working with denial.
AB  - The author discusses a strategy of working with chronically impaired dual
      diagnosis patients who are in denial of their substance abuse problems. It is
      argued that due to a number of unique features among such patients, directly
      confronting denial and insisting on abstinence will not be effective for many of
      these patients. Instead, it is suggested that patients' continued substance use
      should be tolerated although at the same time be made a focus of treatment.
      Techniques are offered which can be utilized to broach the denial of this
      challenging patient population. Types of patients not suitable for this approach
      are also discussed.

PMID- 8308934
TI  - The clinical management of HIV-related dementia and other memory disorders in the
      residential drug treatment environment.
AB  - Human immunodeficiency virus (HIV)-related dementia and other memory and
      attention disorders are described in terms of etiology, incidence, and symptoms.
      Assessment for cognitive impairment includes basic screening (examples are
      given), or a thorough neuropsychological evaluation. Implications for treatment
      within the residential drug treatment environment include: (a) providing accurate
      information to staff and residents; (b) identifying residents' anticipatory
      anxiety; (c) supportive counseling of residents; (d) coaching residents in the
      use of coping strategies; (e) creating environmental support; and (f) frequent
      reassessment of treatment goals, including the appropriateness of independent
      living. Helpful concrete suggestions are listed.

PMID- 8308935
TI  - Women opiate users' perceptions of treatment services in New York City.
AB  - This paper focuses on the treatment experiences of women opiate users in New York
      City. Historically, drug research has used male samples, and drug treatment
      programs have been based upon the concerns of men. Treatment counselors and
      administrators are typically male, and female clients are frequently outnumbered
      by male clients. In addition, unique needs of women are not addressed. Primary
      among these needs is child care, a provision that is not a standard feature of
      most programs. Additionally, many women opiate users may be in dysfunctional
      families and/or have histories of sexual victimization that may require special
      counselling. Using data from 208 women drug users who had been in an opiate
      treatment program, this paper examines their perceptions of the extent to which
      these programs incorporate women's distinctive concerns and the degree to which
      such provisions are affected by the perceived numbers of women clients in these
      programs.

PMID- 8308936
TI  - Behavioral response to buspirone in cocaine and phencyclidine withdrawal.
AB  - The effects of buspirone in treating cocaine and phencyclidine (PCP) withdrawal
      were studied. Withdrawal symptoms of these two street-drugs are thought to be due
      to norepinephrine, dopamine and possibly serotonin depletion. Buspirone acts by
      enhancing dopaminergic and noradrenergic firing as well by suppressing
      serotonergic activity. Thirty-two cocaine abusers and 24 PCP abusers were
      withdrawn over a 30-day period. Half of each group received buspirone 10 mg
      t.i.d. and the other half 10 mg placebo t.i.d. In the cocaine group, buspirone
      was significantly more effective from the fifth day onward. In the PCP group,
      significant improvement was seen on the thirtieth day. Delayed effectiveness in
      PCP is thought due to its actions at other neurotransmitter sites.

PMID- 8308937
TI  - Methadone combined with clonidine versus clonidine alone in opiate
      detoxification.
AB  - The availability and use of a methadone/clonidine combination versus clonidine
      alone in opiate detoxification were studied. In Phase I of the study, a
      sequential combination of methadone followed by clonidine was utilized in those
      patients presenting with a primary diagnosis of opiate dependence. During the
      Phase II of the study, only clonidine was available. Medications were
      administered only if the history and clinical findings indicated impending or
      acute opiate withdrawal syndrome. Overall, there was no difference between the
      Phase I and Phase II groups when the number of opiate dependent admissions,
      patients completing detoxification, and the patients completing a follow-up
      rehabilitation program were compared. However, the patients in Phase I whose
      clinical symptomatology warranted the use of methadone were more likely to
      complete the detoxification program when compared to the patients in Phase II who
      received clonidine only. There was no difference between the two groups in
      completion of a follow-up rehabilitation. Detoxification with clonidine alone was
      more likely to be successful if the patient has had prior detoxification
      experience with methadone or if there was a secondary dependence of alcohol,
      sedative, or tranquilizer present coexisting with the primary opiate dependence
      diagnosis.

PMID- 8308938
TI  - Chemical dissociation in adults sexually victimized as children: alcohol and drug
      use in adult survivors.
AB  - Using a structured diagnostic interview, 65.9% of a clinical group of adult
      survivors of childhood sexual abuse met DSM-III-R criteria for lifetime
      prevalence of drug or alcohol abuse or dependence. Only 4.6% of the total were
      still using drugs or alcohol at the time of testing. Childhood risk factors
      predicted those survivors who used drugs or alcohol with users coming from more
      chaotic home environments. The data supports the hypothesis that many adults
      sexually victimized as children use substances to "chemically dissociate."

PMID- 8308939
TI  - Alcohol and cocaine abusers 6 months after traditional treatment: do they fare as
      well as problem drinkers?
AB  - Problem drinkers (N = 49) and individuals presenting with both alcohol and
      cocaine problems (N = 51) admitted to a traditional 28-day alcoholism treatment
      milieu were compared on their psychosocial, psychological, neuropsychological
      functioning and substance abuse at admission as well as at six months
      posttreatment follow-up. On admission, alcohol and cocaine patients were younger,
      more likely to live alone or with their family of origin, to report having
      started using alcohol at an earlier age, to have fewer alcohol-related problems
      and to have fewer years of but more diversity in their substance abuse than the
      alcohol-only patients. Otherwise both groups were more similar than different on
      psychosocial, psychological and neuropsychological dimensions. At six-months
      posttreatment, both groups showed similar improvement on most dimensions of
      functioning measured. However, a significantly greater proportion of the alcohol
      and cocaine abusers admitted to having relapsed in the previous six months,
      reported significantly fewer average days of abstinence than the alcohol group
      since terminating treatment, and were more likely to present urine specimens
      indicative of recent substance abuse at the six-month follow-up interview. Thus,
      traditional approaches to alcoholism treatment may be less effective in
      establishing abstinence for individuals with both alcohol and cocaine problems.
      Adaptations to treatment to reduce the risk for relapse faced by alcohol and
      cocaine abusers in such milieu are discussed.

PMID- 8308940
TI  - Detected heroin use in an Australian methadone maintenance program.
AB  - A reanalysis was undertaken of survey and retrospective urinalysis data on
      patients remaining in an abstinence-oriented, public methadone maintenance
      program in Sydney, Australia. A comparison of urinalysis results with those of
      previous reports of Australian methadone programs suggests that the clinic's
      disciplinary program failed to reduce detected heroin use; morphine was detected
      in 27% of urine specimens. Women, those with a partner in methadone maintenance,
      and exprisoners were significantly more likely to submit morphine positive
      urines. When account was taken of subjects' General Health Questionnaire scores
      in a second logistic regression model, the more psychologically disturbed
      patients were one fifth as likely to submit a morphine positive specimen as the
      less disturbed. This and other findings are interpreted as indicating that
      psychologically disturbed patients who continued to use heroin were more likely
      to be expelled from or otherwise leave treatment than the less psychologically
      disturbed who continued to use heroin.

PMID- 8308941
TI  - Treatment and services for drug users in Britain.
AB  - The pattern of British drug service provision was transformed during the late
      1980s. Policy makers and service providers recognised the need for a more
      flexible response to changing drug trends and client needs; consequently
      community-based services proliferated. HIV has had considerable impact on the
      working approach of many agencies, where harm minimisation is now the immediate
      goal. This article provides an overview of patterns of drug use and drug service
      provision in Britain.

PMID- 8308942
TI  - Acupuncture treatment for drug abuse: a technical review.
AB  - Conflicting opinions exist regarding the efficacy of acupuncture for the
      treatment of substance abuse. On October 23, 1991, the National Institute on Drug
      Abuse (NIDA) sponsored a technical review to discuss this issue. The purpose of
      the meeting was to review the current status of research regarding acupuncture
      treatment for drug abuse and to propose directions for future studies. This
      report represents a summary of the meeting which consisted of presentations by
      individuals currently involved in acupuncture treatment and discussions by a
      panel of experts in the field of substance abuse treatment research.

PMID- 8308943
TI  - Changes concurrent with initiation of abstinence from cocaine abuse.
AB  - In an exploration of changes that occur with initiation of cocaine abstinence,
      this study examined treatment outcomes in four domains--behavior (cocaine use),
      affect (depression), cognition (schematic self-representations), and
      psychophysiology (reactivity to drug cues). Nineteen patients initially entered
      this 8-week outpatient psychopharmacotherapy trial for the treatment of cocaine
      dependence. Thirteen completed treatment, and eleven maintained abstinence during
      the last four weeks of the study. In addition to a demonstrated change in their
      cocaine-using behavior, these "abstainers" reported reduced depression, increased
      congruency with "ideal" self-schemas, increased discrepancy with "addict" self
      schemas, and generally more positive self-representations. In addition,
      "abstainers" reported reduced posttreatment craving in the presence of cocaine
      cues, but evidenced no change in physiological reactivity. Implications of these
      findings for research and treatment are discussed.

PMID- 8308944
TI  - Program changes and retention on methadone.

PMID- 8308946
TI  - Prediction of acetaminophen concentrations in overdose patients using a Bayesian
      pharmacokinetic model.
AB  - A pharmacokinetic program using population-based parameter estimates and a
      Bayesian forecasting model was retrospectively evaluated for predicting
      acetaminophen serum concentrations in overdose patients. Dynamic disposition
      factors known to affect acetaminophen disposition (emesis, activated charcoal, N
      acetylcysteine, etc.) were included in the program. Twenty six patients who
      reported an acetaminophen ingestion of at least 70 mg/kg within 24 h of
      presentation to the hospital and had at least one measured acetaminophen
      concentration were included. Prediction of initial acetaminophen concentrations
      using only population-based parameter estimates resulted in a percent mean error
      (%ME) and percent mean absolute error (%MAE) of 9.3 and 42.2, respectively. Using
      only the initial concentration as feedback, the Bayesian forecasting model
      accurately predicted the second acetaminophen concentration (%ME = 4.0, %MAE =
      23.6). The Bayesian model also accurately predicted all concentrations within 8 h
      of the ingestion (%ME = 10.6, %MAE = 24.0). The prediction of concentrations
      between 2 to 4 h and 4 to 4.5 h after ingestion with only population-based
      parameter estimates resulted in %ME of 17.0 and 13.2, respectively, and %MAE of
      36.5 and 35.1, respectively. Our data suggests that acetaminophen serum
      concentrations occurring within the first 4.5 h after ingestion can be reliably
      predicted by the set of population-based parameter estimates evaluated. Once a
      single acetaminophen concentration is available, the Bayesian forecasting model
      can accurately predict subsequent concentrations within the first 8 h after an
      acetaminophen ingestion.

PMID- 8308945
TI  - Retrospective analysis of calls to poison control centers resulting from exposure
      to the insect repellent N,N-diethyl-m-toluamide (DEET) from 1985-1989.
AB  - This study analyzed 9,086 human exposures involving N,N-diethyl-m-toluamide-
      containing insect repellents that were reported to Poison Control Centers from
      1985-1989. Nearly two-thirds of those exposed had no adverse effects or only
      experienced minor symptoms that resolved rapidly. Symptoms were more likely to
      occur after ocular or inhalation exposures and least likely to occur if the
      product was ingested. The only reported death occurred in a patient who
      suicidally ingested 8 oz of an insect repellent containing N,N-diethyl-m
      toluamide. Five patients may have experienced a serious or potentially life
      threatening effect but the poison center record did not provide unequivocal
      substantiation of the effect or clearly establish N,N-diethyl-m-toluamide as the
      causative agent. From the analysis of those patients calling Poison Control
      Centers, it appears the risk of serious medical effects with the labeled use of
      N,N-diethyl-m-toluamide-containing insect repellents is low in comparison with
      its reported annual use by about 30% of Americans. For patients contacting Poison
      Control Centers, the occurrence of adverse effects appears to be related to the
      route of exposure rather than age or gender of the patient or the concentration
      of N,N-diethyl-m-toluamide in the product.

PMID- 8308947
TI  - Acid-base abnormalities associated with cocaine toxicity in emergency department
      patients.
AB  - There is little information on the prevalence and clinical presentation of acid
      base abnormalities associated with cocaine toxicity. To address these issues,
      arterial blood gas results were evaluated in 156 cocaine-associated emergency
      department patient visits. Arterial blood gas results were obtained as part of
      the patient's clinical assessment. The majority of patients (52%) had a normal pH
      (7.35 to 7.45). Thirty-three percent of patients were acidotic, with a pH between
      6.4 and 7.35. In 33 patients the acidosis was metabolic, with a HCO3- of 14 +/- 6
      mmol/L. The acidosis was primarily respiratory in 18 patients, with evidence of
      hypoventilation. Hypoventilation was generally secondary to chest trauma or
      decreased mental status. Alkalosis (pH > 7.45) was observed in 15% of patients,
      and was usually respiratory, as evidenced by tachypnea and a low PCO2. These
      results indicate that metabolic and respiratory acid-base abnormalities are
      common during cocaine toxicity. Acidosis and alkalosis were associated with
      numerous patient presentations, including chest pain, shortness of breath,
      decreased mental status, trauma, and seizures. Acid-base abnormalities do not
      appear to be associated with a specific route of cocaine self-administration.
      Patients with a history of potential cocaine toxicity should be evaluated for
      acid-base abnormalities.

PMID- 8308948
TI  - Hypokalemia, hyperglycemia and plasma catecholamine activity after severe
      theophylline intoxication.
AB  - To determine if differences in the rate of hypokalemia and hyperglycemia between
      victims of acute versus chronic theophylline intoxication relate to alterations
      in plasma catecholamine activity, we evaluated plasma catechols in three groups
      of patients: victims of acute theophylline intoxication (n = 10), chronic
      theophylline overmedication (n = 3), and healthy controls (n = 6). There were no
      differences in peak serum theophylline concentration between acute and chronic
      groups (86.6 vs 73.0 mcg/mL, p = NS). Among those with acute intoxication mean
      (+/- SEM) serum potassium was 2.80 +/- .16 mEq/L while mean serum glucose was 208
      +/- 26 mg/dL. In contrast, those with chronic intoxication had a mean serum
      potassium of 4.10 +/- .70 mEq/L with a mean serum glucose of 139 mg/dL (p < .0001
      and p < .04 for between-group potassium and glucose, respectively). Potassium and
      glucose concentrations of those with chronic theophylline intoxication were
      similar to those of controls. Plasma epinephrine was higher in those with acute
      theophylline intoxication than in victims of chronic overmedication and controls
      (282 vs 133 vs 58 pg/mL, p < .003). Plasma norepinephrine and dopamine in
      contrast were significantly higher in those with chronic overmedication than in
      those with acute intoxication and controls (norepinephrine 1395 vs 965 vs 268
      pg/mL, p < .008; dopamine 198 vs 148 vs 39 pg/mL, p < .009). These data suggest
      that the pattern of glucose and potassium disturbances after acute theophylline
      intoxication parallel differences in plasma epinephrine concentrations. This
      supports theories that hypokalemia is the result of enhanced beta-2 receptor
      stimulation.

PMID- 8308949
TI  - Phenthoate metabolites in human poisoning.
AB  - Five metabolites were detected in the plasma and urine of a patient following
      ingestion of the organophosphate insecticide, phenthoate. Intact phenthoate was
      detected only in gastric lavage fluid. After methylation of acidic extracts of
      plasma and urine, phenthoate acid, demethyl phenthoate, demethyl phenthoate oxon
      acid, demethyl phenthoate S-isomer, and demethyl phenthoate acid S-isomer were
      identified with synthesized phenthoate analogues by gas chromatography and gas
      chromatograph-mass spectrometry. The main metabolites were phenthoate acid and
      demethyl phenthoate oxon acid. Although demethyl phenthoate oxon acid was a
      significant metabolite, no phenthoate oxon, phenthoate oxon acid or demethyl
      phenthoate oxon were detected. If the oxon was formed in the patient, it may have
      been rapidly degraded by carboxylesterase or glutathione transferase to demethyl
      phenthoate oxon acid.

PMID- 8308950
TI  - Organophosphate poisoning: peripheral vascular resistance--a measure of adequate
      atropinization.
AB  - We report severe organophosphate poisoning complicated by hypotension and
      ischemic sequelae in two patients with pre-existing vascular disease. Both
      patients had a low total peripheral resistance and high cardiac output that were
      significantly reversed by doses of atropine in excess of those required to
      control other muscarinic symptoms. Cerebral infarcts and gangrene requiring a
      below knee amputation were complications of the poisonings. It is proposed that
      the ischemic complications are due to paradoxical vasoconstriction by
      acetylcholine at sites of endothelial injury. One patient, who had taken
      fenthion, also had a significantly delayed peak and prolonged, 2-3 week, systemic
      toxicity. We propose that stability of the plasma cholinesterase at 6 to 8 h
      after temporarily suspending oxime provides a rapid guide to the duration of
      therapy, especially in patients whose complications make clinical assessment
      difficult.

PMID- 8308951
TI  - Cutaneous exposure to warfarin-like anticoagulant causing an intracerebral
      hemorrhage: a case report.
AB  - A case of intercerebral hematoma due to warfarin-induced coagulopathy is
      presented. The 39-year-old woman had spread a warfarin-type rat poison around her
      house weekly using her bare hands, with no washing post application. Percutaneous
      absorption of warfarin causing coagulopathy, reported three times in the past, is
      a significant risk if protective measures, such as gloves, are not used. An
      adverse drug interaction with piroxicam, which she took occasionally, may have
      exacerbated the coagulopathy.

PMID- 8308952
TI  - Inhalation abuse of fentanyl patch.
AB  - A 36-year-old male became intoxicated from fentanyl by heating and inhaling the
      contents from a fentanyl patch. He collapsed immediately after one inhalation
      with a respiratory rate of 6/m, heart rate of 120 bpm, and unobtainable blood
      pressure. He responded to a naloxone injection. Inhalation abuse of fentanyl base
      is a novel phenomenon. In two studies of nebulized fentanyl at doses of 64-318
      micrograms of fentanyl base, analgesia was achieved with these doses, and small
      decreases in respiratory rate occurred with the larger dose. The greater
      absorption expected from inhaling the volatilized product, the large quantity of
      fentanyl available in a patch, and the high potency of fentanyl produces a high
      potential for abuse and overdose.

PMID- 8308953
TI  - Osmolar gap with minimal acidosis in combined methanol and methyl ethyl ketone
      ingestion.
AB  - Methyl ethyl ketone is a common solvent but data on overdose in humans are
      scarce. We report a case of co-ingestion of methyl ethyl ketone together with
      methanol associated with a hyperosmolar coma without anion gap metabolic
      acidosis. Blood levels of methyl ethyl ketone and its metabolite, 2-butanol,
      indicated that this solvent did contribute approximately 20 mosm/L to an observed
      osmolar gap of 99 mosm/L. At the levels detected, methyl ethyl ketone may have
      inhibited methanol metabolism, contributing to the low serum formate (1.3 mmol/L)
      and normal anion gap despite a blood methanol of 67 mmol/L.

PMID- 8308954
TI  - GLC determination of serum-ethylene glycol, interferences in ketotic patients.

PMID- 8308955
TI  - Osmol gap vs. residual osmolality or excess osmolal gap.

PMID- 8308956
TI  - Validity of AAPCC data base.

PMID- 8308957
TI  - Hereditary papillary renal cell carcinoma.
AB  - We describe a 3 generation family with members affected with papillary renal cell
      carcinoma, an uncommon histological type of renal cell carcinoma. Multiple tumors
      of varying size were present in both kidneys of affected family members. The
      disorder was not linked to polymorphic markers on chromosome 3p and there was no
      loss of heterozygosity at loci on 3p in renal tumors. The results suggest the
      presence of a renal cell carcinoma gene not located on 3p that predisposes to
      renal cell carcinoma with a distinct histological appearance. The inherited
      disorder in this family appears to be different from recognized hereditary cancer
      syndromes.

PMID- 8308958
TI  - Hydatid disease of the kidney: evaluation and features of diagnostic procedures.
AB  - We discuss 8 patients with hydatid cystic disease of the kidney. Diagnostic
      procedures included eosinophil count, Casoni's skin test, Ghedini-Weinberg
      complement fixation test, abdominal x-ray, excretory urogram, ultrasonography and
      computerized tomography. The combined findings of these different modalities aid
      greatly in establishing the correct diagnosis.

PMID- 8308959
TI  - Clinical and biochemical differences in patients with pure calcium oxalate
      monohydrate and calcium oxalate dihydrate kidney stones.
AB  - To examine the factors and patient characteristics predisposing to formation of
      calcium oxalate monohydrate or calcium oxalate dihydrate kidney stones, we
      compared blood and 24-hour urine tests, gender distribution and patient age in 2
      groups of patients with pure calcium oxalate monohydrate (422) and calcium
      oxalate dihydrate (68) stones treated at the lithotripsy unit of the Wellesley
      Hospital and University of Toronto during 4 years. The calcium oxalate
      monohydrate group included relatively more women (31% versus 16% in the calcium
      oxalate dihydrate group, chi-square 7.89, p = 0.005). Patients were older in the
      calcium oxalate monohydrate group (59 +/- 13 versus 51 +/- 13 years, p = 0.001).
      The calcium oxalate monohydrate group had lower urinary calcium (4.19 +/- 2.34
      versus 7.19 +/- 3.38 mmol. per day, p < 0.0001), calcium oxalate relative
      saturation rate (6.9 +/- 3.9 versus 8.9 +/- 3.3, p = 0.001), brushite relative
      saturation rate (0.7 +/- 0.8 versus 1.2 +/- 0.9, p = 0.0001) and urinary pH (5.72
      +/- 0.75 versus 5.93 +/- 0.72). When corrected for patient age and gender, the
      calcium oxalate dihydrate group still had higher urine calcium levels. Higher
      urine pH in the calcium oxalate dihydrate group was age-related. In summary, we
      present evidence that calcium oxalate dihydrate stones are relatively more common
      among younger male patients with higher urine calcium levels and higher urine pH.

PMID- 8308960
TI  - Reassessment of the value of post-vascularization biopsy performed at renal
      transplantation: the effects of arteriosclerosis.
AB  - Between January 1, 1984 and December 31, 1991, 471 cadaver renal transplants were
      performed. We reviewed 130 transplants, which were biopsied 30 minutes to 1 hour
      after the establishment of renal allograft blood flow. Analysis showed a
      significant difference in 2-year graft survival rate between the groups with and
      without arteriosclerosis (71.8% versus 65.9%, p < 0.05). Arteriosclerotic changes
      were noted more frequently in biopsies from older donors (37 versus 28 years, p <
      0.005). There was also a difference in ischemic time between the groups with and
      without tubular degeneration (30.1 hours versus 26.7 hours, p < 0.02), which did
      not correlate with the need for dialysis in the perioperative period (48% versus
      49%, p > 0.8).

PMID- 8308961
TI  - Rescue of renal transplants with distal ureteral complications by pyelo
      pyelostomy.
AB  - Secondary ureteroneocystostomy is the procedure most commonly used for repair of
      ureteral stenosis or necrosis in renal transplant patients. However, when the
      transplant ureter available for reconstruction is too short, ureteropyelostomy is
      the standard procedure. Another option is pyelo-pyelostomy, which has been used
      infrequently to date. Between 1979 and 1988 we managed 6 patients (4 men and 2
      women 42 to 62 years old) with renal allografts who required repair of the
      transplant ureter for long segmented ureteral necrosis (3), long segmented
      ureteral stenosis (2) and an iatrogenic lesion of the ureter (1) with pyelo
      pyelostomy. Of the 6 patients 2 had undergone previous rescue operations. Pyelo
      pyelostomy with the renal pelvis of the graft was performed as first described by
      Gil-Vernet and Caralps in 1968. Median followup was 6 years (range 3 to 12
      years). Two patients died of chronic rejection and pulmonary embolism,
      respectively. Four patients are still alive with functioning transplants and
      serum creatinine levels of less than 210 mumol/l. According to our experiences
      with 6 patients, we believe that pyelo-pyelostomy is a promising rescue maneuver
      that is worth consideration in cases of total or subtotal ureteral necrosis and
      long segmented ureteral stenosis after renal transplantation.

PMID- 8308962
TI  - Cyclosporine versus azathioprine: a 5-year followup of 200 consecutive cadaver
      renal transplant recipients.
AB  - When cyclosporine was introduced as an immunosuppressive agent, there was concern
      that cyclosporine could be detrimental to long-term renal allograft function and
      survival. In response to this concern, we report a 5-year followup of 200
      consecutive renal transplant recipients among whom initial immunosuppression and
      risk factors were similar except for the substitution of cyclosporine for
      azathioprine in the second 100 recipients. The azathioprine and cyclosporine
      groups had similar 1-year (89% versus 91%) and 5-year (74% versus 80%) patient
      survival rates. Cyclosporine treated patients had superior 1-year (83% versus
      58%) and 5-year (61% versus 29%) graft survival rates. At the 5-year interval,
      cyclosporine treated grafts had an elevated, yet stable, mean serum creatinine
      level compared to azathioprine treated grafts. Despite ongoing mild renal
      dysfunction in cyclosporine treated grafts, cyclosporine does not induce an
      inexorable decrease in graft function and continues to provide long-term graft
      survival superior to azathioprine.

PMID- 8308963
TI  - Ongoing advances in renal transplantation.

PMID- 8308964
TI  - Autoantibodies in interstitial cystitis.
AB  - We have identified and partially characterized autoantibodies from the sera of
      patients with interstitial cystitis. Our characterization included initial
      screening by antinuclear antibody testing on human HEp-2 cell substrate and mouse
      kidney/stomach tissue substrate, titering and subtyping of positive sera, and
      Western blotting to identify target autoantigens. Of 96 interstitial cystitis
      patients 35 (36%) were positive for antinuclear antibodies at titers of 1/40 or
      greater. Among the antinuclear antibody patterns observed 24 were dense fine
      nuclear speckles, 7 were nucleolar, 3 were mitochondrial and 1 was coarse nuclear
      speckles. All but 4 of the antinuclear antibody positive sera were exclusively of
      the IgG class. As determined by unique antinuclear antibody staining patterns and
      by specificities on Western blots, interstitial cystitis autoantibodies appear to
      recognize novel autoantigens not previously described in patients with systemic
      autoimmune diseases, such as lupus, scleroderma and Sjogren's syndrome.

PMID- 8308965
TI  - Primary methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy and
      bladder preservation in locally invasive bladder cancer: a 5-year followup.
AB  - A phase 2 protocol was designed for conservative treatment of muscle invasive
      transitional cell carcinoma of the bladder and consisted of primary methotrexate,
      vinblastine, doxorubicin and cisplatin chemotherapy followed by bladder sparing
      surgical reevaluation and surveillance. Of 36 patients 30 completed the protocol
      and were followed for at least 5 years. Initial complete response to chemotherapy
      was noted in 14 patients (47%, 95% confidence interval 30 to 64%) and complete
      responses were more common with low stage tumors. After chemotherapy the bladder
      was preserved in 18 patients (60%) but at 5 years only 6 (20%, 95% confidence
      interval 6 to 34%) were alive with the bladder intact. Bladder preservation was
      possible only in the complete response group. The long-term followup showed that
      after 5 years 16 patients (53%) were alive and 15 (50%, 95% confidence interval
      32 to 68%) were disease-free. When patients were stratified according to the type
      of response to chemotherapy, the 5-year disease-free survival was 79% versus 25%
      for the complete response and the partial or no response groups, respectively (p
      < 0.01). According to these results and considering the highly selective nature
      of our study, primary methotrexate, vinblastine, doxorubicin and cisplatin
      chemotherapy compared to standard treatments does not improve the overall
      survival rate, nor does it allow for bladder preservation in most cases of
      locally invasive transitional cell carcinoma of the bladder. This approach seems
      only to segregate patients with a greater chance for long-term survival in the
      complete response group and a poor outcome for partial/no response patients
      regardless of early salvage bladder extirpation.

PMID- 8308966
TI  - Pattern of failure and survival of patients with metastatic urothelial tumors
      relapsing after cis-platinum-based chemotherapy.
AB  - Cis-platinum-based chemotherapy combinations have improved the outcome of
      patients with metastatic urothelial tumors, since two-thirds of these patients
      respond to treatment. Nevertheless, the majority of such patients have relapse
      within a median of 12 months. To define the pattern of failure and subsequent
      outcome, we retrospectively assessed 58 consecutive patients with relapse after
      prior response to cis-platinum-based combination chemotherapy. Of the patients
      who presented initially with local-regional metastases, 74% had relapse with
      involvement of a similar site, while only 26% of these patients had visceral
      metastases at relapse. The median survival after relapse was 9 months, and
      parameters associated with longer survival were local-regional relapse (10.7
      months) and response to salvage chemotherapy (12.6 months). These data suggest
      that select patients with urothelial tumors and local-regional metastases may
      benefit from consolidation therapy with surgery or radiotherapy after maximum
      response to chemotherapy.

PMID- 8308967
TI  - A pilot study of chemotherapy alternating with twice-a-day accelerated radiation
      therapy as an alternative to cystectomy in muscle infiltrating (stages T2 and T3)
      cancer of the bladder: preliminary results.
AB  - Laboratory studies have suggested that rapidly alternating chemotherapy and
      accelerated radiation therapy might act synergistically. We evaluated the
      toxicity and effectiveness of this approach in muscle infiltrating transitional
      cell carcinoma of the bladder in patients who were poor risks for or who refused
      cystectomy. We treated 18 men and 3 women with stage T2 or T3 transitional cell
      carcinoma of the bladder by transurethral resection, followed by 3 cycles of
      chemotherapy (during weeks 1, 4 and 7) rapidly alternating with 3 cycles of twice
      a-day radiation therapy (during weeks 2, 5 and 8). Chemotherapy consisted of
      methotrexate, vinblastine, doxorubicin and cisplatin. The total dose of radiation
      therapy was 5,400 to 6,000 cGy, during 6 1/2 weeks and the total duration of
      chemotherapy and radiation therapy was 7 1/2 weeks. One patient died of
      hematological toxicity during treatment. With a median followup of 2 years (range
      0.5 to 5.5 years) the observed survival rate was 72% at 2 years and 60% at 3
      years. To date, only 1 patient (5%) had recurrence of invasive cancer in the
      pelvis. Only 3 others (15%) had carcinoma in situ but to date none has required
      cystectomy. Bladder function was normal in 15 of 18 evaluable patients (83.5%).
      This pilot study suggests that chemotherapy alternating with radiation therapy
      produced an encouraging survival rate without cystectomy and deserves further
      study. These patients require continued surveillance for carcinoma in situ.

PMID- 8308968
TI  - The cure of bladder cancer: the need for multidisciplinary efforts.

PMID- 8308969
TI  - Periurethral injection of autologous fat for the treatment of sphincteric
      incontinence.
AB  - A total of 15 women with stress incontinence and 6 men with post-prostatectomy
      sphincteric incontinence underwent periurethral injection of autologous fat while
      under local anesthesia. The fat was harvested from the abdominal wall by
      liposuction. Preoperative evaluation consisted of a micturition diary,
      questionnaire, semiquantitative pad test, cystoscopy and urodynamics. Sequential
      injections were performed at 1 to 3-month intervals. Results were assessed by
      subjective patient scores, pad tests and clinical evaluation performed at
      intervals. Followup was 12 to 30 months (mean 18). Only 1 man and none of the
      women with urethral hypermobility had lasting improvement. Of the 15 women 12 had
      intrinsic sphincteric deficiency (type 3 stress incontinence) and they were our
      most successful group. Of the 12 women 10 (83%) were improved (mean score of 8.8
      7 before injection compared to 1.87 after injection) at 1 month following the
      initial injection. Of the 9 patients who continued with the treatment 7 (78%)
      noticed lasting improvement objectively and subjectively after 1 to 4 injections
      (mean 2.4). We believe that this technique shows sufficient promise as an
      alternative therapy for sphincteric incontinence to warrant continued clinical
      investigation.

PMID- 8308970
TI  - Impotence and chronic renal failure: a study of the hemodynamic pathophysiology.
AB  - A retrospective multi-institutional study was performed to document and
      characterize the arterial vascular disease in the hypogastric-cavernous arterial
      bed and/or veno-occlusive dysfunction of the corpora cavernosa in patients with
      end stage renal disease. We evaluated 20 impotent patients (mean age 40 +/- 9
      years) with chronic renal failure using pharmaco-cavernosometry and
      pharmacocavernosography (4 also underwent pharmaco-arteriography). Patients were
      divided into groups based on the treatment (14 with renal transplantation and 6
      with hemodialysis or peritoneal dialysis), as well as by history of vascular risk
      factors (16 with and 4 without risk factors). Of the patients 19 revealed
      abnormal intracavernous pressure responses to repeated intracavenous injections
      of vasoactive agents implying vascular disease of the penis. Cavernous artery
      occlusive disease was found in 78% of the patients. All patients who underwent
      arteriography had diffuse atherosclerotic disease of the distal penile arteries.
      Corporeal veno-occlusive dysfunction was found in 90% of the patients, of whom
      60% had diffuse pan-cavernous leakage involving the dorsal, cavernous and crural
      veins, glans penis and corpus spongiosum. This renal failure-associated vascular
      disease of the penis was found to occur independently of the presence of known
      systemic atherosclerotic vascular risk factors. Patients who underwent early
      treatment of the uremia by renal transplantation had vasculogenic impotence only
      in the case of rejection of the renal transplant, suggesting that early renal
      transplantation may delay or prevent the development of the penile vasculopathy.
      The most likely pathophysiology of the vascular impairment includes renal failure
      associated atherosclerosis, and renal failure-associated hypoxia changes of the
      contractile (smooth muscle) and structural (collagen/elastin) components of the
      erectile tissue. Strategies for future research and clinical therapies are
      suggested.

PMID- 8308971
TI  - Sperm antibody status does not correlate with egg penetration ability.
AB  - During a 6-month period 59 semen specimens were subjected to the direct
      immunobead test and 12 were positive (15% or more of sperm bound by IgA or IgG to
      the head, mid piece or principal piece of the tail, for an incidence of 20%).
      Mean motility and forward progression (scale of 0 to 4) were 47% (range 10 to 80)
      and 1.7 (range 1 to 3), respectively, in the positive test group, whereas these
      values were 53% (range 1 to 90) and 2.2 (range 1 to 3), respectively, in the
      negative test group. Sperm penetration assay was performed on 11 of the 12 direct
      immunobead test positive specimens. A normal sperm penetration assay score was
      noted in 5 of the 11 specimens (46%), a subfertile score in 4 (36%) and an
      infertile score (no penetrations) in 2 (18%). The incidence of scores in these 3
      subcategories of fertility status in the direct immunobead test positive group
      did not differ significantly from distribution of scores from all 87 sperm
      penetration assays performed at our laboratory during the same period: normal--39
      of 87 (45%), subfertile--35 (40%) and infertile--13 (15%). Furthermore, there was
      no pathognomonic binding pattern for those antibody positive patients with
      subfertile or infertile scores. In conclusion, sperm antibody positivity is
      typically independent of egg penetration ability, there is no pathognomonic
      antibody binding pattern for poor egg penetration and there is a tendency for
      antibody positive sperm to have a lower percentage of motility and forward
      progression.

PMID- 8308972
TI  - Demonstration of a rational strategy for human prostate cancer gene therapy.
AB  - The potential efficacy and clinical feasibility of gene therapy for prostate
      cancer were tested. Efficacy was tested using the Dunning rat prostate carcinoma
      model. Rats with anaplastic, hormone refractory prostate cancer treated with
      irradiated prostate cancer cells genetically engineered to secrete human
      granulocyte-macrophage colony-stimulating factor (GM-CSF) showed longer disease
      free survival compared to either untreated control rats or rats receiving
      prostate cancer cell vaccine mixed with soluble human GM-CSF. A gene modified
      prostate cancer cell vaccine thus provided effective therapy for anaplastic,
      hormone refractory prostate cancer in this animal model. An evaluation of the
      clinical feasibility of gene therapy for human prostate cancer based on these
      findings was then undertaken. Prostate cancer cells from patients with stage T2
      prostate cancer undergoing radical prostatectomy were first transduced with MFG
      lacZ, a retroviral vector carrying the beta-galactosidase reporter gene.
      Efficient gene transfer was achieved in each of 16 consecutive cases (median
      transduction efficiency 35%, range 12 to 65%). Cotransduction with a drug
      selectable gene was not required to achieve high yield of genetically modified
      cells. Histopathology confirmed malignant origin of these cells and
      immunofluorescence analysis of cytokeratin 18 expression confirmed prostatic
      luminal-epithelial phenotype in each case tested. Cell yields (2.5 x 10(8) cells
      per gram of prostate cancer) were sufficient for potential entry into clinical
      trials. Autologous human prostate cancer vaccine cells were then transduced with
      MFG-GM-CSF, and significant human GM-CSF secretion was achieved in each of 10
      consecutive cases. Sequential transductions increased GM-CSF secretion in each of
      3 cases tested, demonstrating that increased gene dose can be used to escalate
      desired gene expression in individual patients. These studies show a preclinical
      basis for proceeding with clinical trials of gene therapy for human prostate
      cancer.

PMID- 8308973
TI  - Transdermal clonidine for ameliorating post-orchiectomy hot flashes.
AB  - To determine the efficacy of transdermal clonidine for alleviating post
      orchiectomy hot flashes, a randomized, double-blind, crossover clinical trial was
      designed including 70 men with a history of prostate cancer who had undergone a
      medical or surgical orchiectomy and were suffering from hot flashes. The results
      of this study demonstrated that clonidine did not significantly decrease hot
      flash frequency or severity. Future research is necessary to find effective means
      of alleviating hot flashes in post-orchiectomy patients.

PMID- 8308974
TI  - Quality of life of incontinent men after radical prostatectomy.
AB  - The impact of urinary incontinence on the quality of life among 50 men (average
      age 67 years) after radical prostatectomy was assessed by a self-administered
      questionnaire. The majority were not restricted by incontinence, whereas 26% of
      the men reported limitations in the usual physical activity and more than half
      reported moderate to severe emotional distress. Of 33 patients evaluated less
      than 5 years postoperatively 26 (79%) would choose surgery again despite
      incontinence, whereas 9 of 17 (53%) evaluated after 5 years were unsure or would
      not. Objective quality of life information may help to improve nonoperative
      intervention strategies for the incontinent patient.

PMID- 8308975
TI  - Lithotripsy of urinary calculi by tunable pulsed dye lasers: a randomized in
      vitro study.
AB  - Pulsed dye laser lithotripsy has been used in the treatment of urinary calculi.
      We compared the efficacy of 2 pulsed dye lasers with different pulse durations in
      lithotripsy. A total of 20 pairs of human kidney stones was matched by size and
      composition, and randomized for laser lithotripsy under identical in vitro
      conditions. Each stone received 150 shocks at sequential energy settings between
      40 and 140 mJ. while in a laser fiber compatible stone basket until complete
      fragmentation occurred. Stone fragments were separated by size and weight. We
      found that the laser with the shorter pulse duration fragmented stones with less
      total energy and produced fewer fragments greater than 3.35 mm. The differences
      were statistically significant.

PMID- 8308976
TI  - Vesical lithiasis: open surgery versus cystolithotripsy versus extracorporeal
      shock wave therapy.
AB  - We compare the different methods of treating vesical calculi to establish the
      most effective and safe modality. Of 128 patients with bladder calculi 5
      underwent an open operation, 80 underwent mechanical cysto-lithotripsy and 43
      underwent extracorporeal shock wave therapy. Severe complications included
      hematuria, bladder perforation and mucosal injury in the mechanical
      cystolithotripsy group. We find extracorporeal shock wave therapy to be a simple,
      effective and safe modality for the management of vesical lithiasis.

PMID- 8308977
TI  - Management of lower pole nephrolithiasis: a critical analysis.
AB  - The results of extracorporeal shock wave lithotripsy (ESWL*) and percutaneous
      nephrostolithotomy for the treatment of lower pole nephrolithiasis were examined
      in 32 consecutive patients undergoing percutaneous nephrostolithotomy at the
      Methodist Hospital of Indiana and through meta-analysis of publications providing
      adequate stratification of treatment results. Of 101 cases managed with
      percutaneous nephrostolithotomy 91 (90%) were stone-free, a result significantly
      better than that achieved with ESWL (1,733 of 2,927 stone-free, 59%). Stone-free
      rates with percutaneous nephrostolithotomy were independent of stone burden,
      whereas stone-free rates with ESWL were inversely correlated to the stone burden
      treated. The morbidity of patients undergoing percutaneous nephrostolithotomy at
      our hospital was minimal, with a mean hospital stay of 4.7 +/- 2.8 days. No blood
      transfusions were required. All patients became stone-free. The percentage of
      urolithiasis patients with lower pole calculi is increasing. Because of the
      significantly greater efficacy of percutaneous nephrostolithotomy for lower pole
      calculi, particularly stones larger than 10 mm. in diameter, further
      consideration should be given to an initial approach with percutaneous
      nephrostolithotomy.

PMID- 8308978
TI  - Interventional urinary stone management.

PMID- 8308979
TI  - Comparative financial analysis of laparoscopic versus open pelvic lymph node
      dissection for men with cancer of the prostate.
AB  - Laparoscopic pelvic lymph node dissection has been applied as a minimally
      invasive staging technique for men with prostate cancer. This procedure has been
      shown to shorten markedly postoperative hospitalization, decrease analgesic
      requirements and shorten convalescence period compared to open pelvic node
      dissection. However, the laparoscopic procedure takes longer to perform and many
      disposable instruments are used, thus increasing the cost. We determine the
      overall cost of laparoscopic versus open pelvic lymph node dissection. Between
      January 1989 and April 1992, 61 men underwent only staging pelvic lymph node
      dissection for cancer of the prostate at a single university teaching hospital.
      Of these patients 11 and 50 underwent open and laparoscopic pelvic lymph node
      dissection, respectively. Information from the hospital business office was
      reorganized into preoperative, intraoperative and postoperative expenses. All
      individual charges were transformed up or down to the dollar amounts of the 1990
      to 1991 fiscal year so as to correct for inflationary changes. Preoperative costs
      were not significantly different between the 2 operative approaches.
      Intraoperative expenses were 52% greater if laparoscopic pelvic lymph node
      dissection was performed and can be explained by the longer operative times and
      use of disposable instrumentation. However, the postoperative period lasted an
      average of 1.61 days following laparoscopic pelvic lymph node dissection.
      Postoperative nursing and analgesic requirements were significantly more for
      patients undergoing open pelvic lymph node dissection. The overall postoperative
      costs following open pelvic lymph node dissection were 280% more expensive than
      for the laparoscopic procedure. The overall total costs were approximately $1,250
      more for laparoscopic pelvic lymph node dissection. Wages lost or earned during
      this period and rapid return to normal activity following laparoscopic pelvic
      lymph node dissection would, in our opinion, justify this additional cost.

PMID- 8308980
TI  - Complications of laparoscopic urological surgery: experience at St. Louis
      University.
AB  - A total of 221 patients underwent laparoscopic surgery at our institution. An
      outcome analysis with regard to type of procedure, success and complications was
      done. Overall, 216 of 221 procedures (97.7%) were performed as originally
      planned. One operation was converted to an open procedure. Complications
      producing morbidity occurred in 33 of 217 patients (15.2%). There was no
      associated mortality. Most complications occurred early in the participating
      surgeons experience. Of the complications 11 (5.0%) were considered major and
      included formation of symptomatic lymphoceles (4 patients), vascular injury (1),
      ureteral transection (1), bladder perforation (1), bowel obstruction (1), cecal
      perforation (1) and cerebrovascular accident (1). One patient had an idiopathic
      reaction to the inhalation anesthetic. Of the 11 major complications 9 occurred
      among 98 patients undergoing pelvic lymphadenectomy and 7 of these occurred among
      a subset of 15 patients undergoing an extended dissection. Adjuvant surgical
      intervention was necessary in 13 patients: celiotomy in 5, laparoscopic
      techniques in 4 and minor surgical procedures or percutaneous techniques in 4.
      Our experience suggests that urological laparoscopic surgery is safe and offers a
      shorter convalescence. However, the technique must be regarded as major surgery,
      associated with a steep learning curve.

PMID- 8308981
TI  - Laparoscopic therapy.

PMID- 8308982
TI  - Percutaneous stone removal with the patient in a flank position.
AB  - We report a case of percutaneous removal of a staghorn calculus that was
      accomplished in a morbidly obese patient while he was in a full flank position.
      In this position, the stone could be successfully accessed and fragmented without
      compromising the pulmonary status of the patient.

PMID- 8308983
TI  - Transurethral clot evacuation from a bladder with a catheter irrigating syringe.

PMID- 8308984
TI  - Percutaneous approach to treatment of Indiana pouch stones.
AB  - Continent urinary diversions have gained popularity during recent years in the
      treatment of patients who require cystectomy. The formation of urinary stones
      remains a possible late complication of urinary diversion. We report the
      successful use of a percutaneous approach to remove stones from an Indiana pouch
      after other methods failed.

PMID- 8308985
TI  - Scrotal ultrasound for evaluation of subacute testicular torsion: sonographic
      findings and adverse clinical implications.
AB  - There is an increased use of scrotal ultrasound in the clinician's office and
      emergency room for the investigation of scrotal pain. The use of real-time
      scrotal ultrasound for the diagnosis of testicular torsion has been described in
      the literature. A false-negative ultrasound examination can postpone the
      diagnosis of torsion and result in testicular loss. We examined 6 patients 1 day
      to 18 years old who had subacute testicular torsion with scrotal symptomatology
      (pain and/or swelling) for longer than 8 hours (range 12 hours to 6 days).
      Scrotal ultrasound was performed as 1 of the initial tests. A common sonographic
      pattern was an inhomogeneous testicle with hypoechoic areas alternating with
      hyperechoic areas and thickening of adjacent scrotal tissue. Another common
      finding was an edematous hyperechoic epididymis and a small hydrocele. In 4 of
      the 6 cases these nonspecific findings suggested a misleading diagnosis of tumor
      or epididymitis and resulted in delay of surgery and testicular loss. Treatment
      was not delayed in only 2 patients in whom the diagnosis of torsion was made
      initially by history and physical examination, and ultrasound was done for
      interest only. Misdiagnosis of intratesticular blood flow and some potential
      pitfalls of scrotal imaging by color Doppler ultrasound are discussed. We
      conclude that real-time scrotal sonography can be misleading in cases of subacute
      testicular torsion and, therefore, it should not be used in this clinical
      setting.

PMID- 8308986
TI  - Large iliac artery aneurysm masquerading as prostate cancer.
AB  - Vascular aneurysms can present with signs and symptoms of urological disease. We
      report on a 74-year-old man who underwent urological referral because of an
      abnormal prostate on rectal examination. Diagnostic evaluation revealed large,
      abdominal aortic and iliac artery aneurysms with prostate and bladder
      displacement.

PMID- 8308987
TI  - Mucinous adenocarcinoma of the prostate and hormone sensitivity.
AB  - We report a case of mucinous adenocarcinoma of the prostate treated successfully
      with androgen ablation followed by laparoscopic lymphadenectomy and total
      perineal prostatectomy. This case demonstrates that mucinous adenocarcinoma of
      the prostate may be hormonally sensitive.

PMID- 8308988
TI  - Re: A simple technique for intraoperatively stenting a transected ureter.

PMID- 8308989
TI  - Re: Management of urinary calculi during pregnancy.

PMID- 8308990
TI  - Re: The value of immediate or early catheterization of the traumatized posterior
      urethra.

PMID- 8308991
TI  - Re: Testis sparing surgery for pediatric epidermoid cysts of the testis.

PMID- 8308992
TI  - Re: Urinary tract infections in healthy university men.

PMID- 8308993
TI  - Early detection of unilateral occlusion of duplicated mullerian ducts: the use of
      serial pelvic sonography for girls with renal agenesis.
AB  - For early detection of unilateral occlusion of duplicated mullerian ducts, serial
      pelvic sonography was performed in 215 girls with known renal agenesis,
      especially following menarche, during the last 6 years. To date, 16 girls with
      unilateral occlusion of duplicated mullerian ducts were detected. We stress the
      value of this modality, which can lead to a prompt diagnosis, and allow for early
      and appropriate surgical intervention.

PMID- 8308994
TI  - Onlay island flap urethroplasty for severe hypospadias: a variant of the
      technique.
AB  - A variant of the onlay island flap urethroplasty in severe hypospadias repair is
      described. The principles of the technique include mobilization of the urethral
      plate without dividing it, release of chordee, creation of a pedicle island flap
      on the dorsal penile skin with redundant vascularized tissue that is transposed
      to the ventral side of the penis by a buttonhole maneuver, and onlay of the flap
      to the mobilized urethral plate, covering all suture lines with a wide pedicle of
      flap. During the last 3 years this operation was performed in 92 patients 12
      months to 19 years old with severe hypospadias. The complication rate was 5%.

PMID- 8308995
TI  - Neonatal testis tumors: a review of the Prepubertal Testis Tumor Registry.
AB  - Since 1980, 338 testis tumors have been registered in the Prepubertal Testis
      Tumor Registry of the American Academy of Pediatrics, Section on Urology. Of
      these tumors 22 occurred in neonates less than 1 month old, of which 7 (31%) were
      diagnosed at birth. The distribution of lesions in this group revealed 6 yolk sac
      tumors, 6 gonadal stromal tumors, 6 juvenile granulosa cell tumors, 2
      gonadoblastomas, 1 teratoma and 1 hamartoma. Preoperative serum alpha-fetoprotein
      levels were available for 10 patients and ranged from 23 to 61,700 ng/ml., which
      is within normal limits. No patient had evidence of metastatic disease at
      presentation. Of the 18 children in whom follow up is available 17 have no
      evidence of disease and 1, who was diagnosed with a yolk sac tumor before the
      advent of chemotherapy, died of metastatic disease before reaching age 1 year.
      Although neonatal testis tumors are rare, they should be considered in the
      differential diagnosis and management of a newborn with a scrotal mass.

PMID- 8308996
TI  - Normal epididymal anatomy in boys.
AB  - It is accepted that a range of epididymal anomalies exists in boys with
      cryptorchidism, varying from ductal patency aberrations to abnormal attachments
      of the epididymis to the testes or even complete absence. Despite several series
      characterizing these variations, there are few studies of normal controls for
      comparison. We document normal epididymal anatomy in boys. During an 18-month
      period ending in 1991, 94 boys (mean age 4.8 years, range 1 month to 18 years)
      underwent inguinal or scrotal exploration unrelated to cryptorchidism. Epididymal
      anatomy was recorded for all exposed testes. Indications for surgery included
      hydrocele or hernia in 85 boys, torsion in 8 and varicocele in 1. A total of 112
      epididymides was examined and the configurations were recorded as type 1-head and
      tail attachment with a "looped" body in 94 of 112 cases (83.9%), type 2-complete
      attachment to the testis in 14 (12.5%), type 3-head attachment only in 3 (2.7%),
      type 4-tail attachment only in 0 (0%), type 5-nonfusion in 1 (0.9%) and type 6
      anomalies of ductal patency in 0 (0%). These data reveal that the most common
      epididymal configuration in normal boys is a looped epididymis with the head and
      tail attached (84%) followed by complete fusion with the testes (12.5%). Other
      variations are rare. Absence of the epididymis was not observed.

PMID- 8308997
TI  - Laparoscopic renal surgery in children.
AB  - A total of 17 laparoscopic renal procedures was performed in children, including
      nephrectomy (10), nephroureterectomy (4), partial nephrectomy (2) and giant renal
      cyst excision (1). Patient age ranged from 4 months to 11 years (average age 34
      months). The average operating time was 2 hours and 15 minutes, ranging from 1
      hour 50 minutes to 2 hours 45 minutes. The usual period of hospitalization was 23
      hours, with the longest being 36 hours for 2 patients. No complications ensued.
      Despite the decreased working space in children, laparoscopic renal surgery
      offers compelling advantages, including short hospitalization, less perioperative
      and postoperative pain, improved cosmesis, earlier return to normal unrestricted
      activities and early return to work for the parents. Methods to accomplish renal
      laparoscopic surgery safely in children are detailed.

PMID- 8308998
TI  - Laparoscopic nephroureterectomy in the child: initial case report.
AB  - Laparoscopy in the pediatric population is beginning to be used for major
      therapeutic procedures. We report the completion of a laparoscopic
      nephroureterectomy and bladder diverticulectomy in a 6-year-old child.

PMID- 8308999
TI  - Detection of interleukin-1 activity in human bladder cancer cell lines.
AB  - Detection of interleukin (IL)-1 activity was studied in two human bladder cancer
      cell lines, T24 and EJ1, and one rat bladder carcinoma cell line, 804G.
      Significantly high proliferation of mouse thymocytes in the assay of IL-1
      activity was observed in the conditioned medium (CM) of T24 cells, indicating
      that the cells released IL-1-like activity. Enzyme-linked immunosorbent assay
      (ELISA) and Northern blot analysis showed the presence of both IL-1 alpha and IL
      1 beta in the CM of T24 cells and expression of mRNAs of both cytokines in the
      cells. Interleukin-1 activity in EJ1 cells, which produced a little activity, was
      induced by E. coli lipopolysaccharide (LPS) while it was not induced in T24 by
      either LPS or other test substances. Conditioned medium of T24 increased
      proliferation of both T24 and EJ1 in cell-growth assay. Further investigation of
      the mode of action and role of cytokines, especially those from tumor cells
      themselves, is necessary in relation to BCG or photodynamic therapy.

PMID- 8309000
TI  - Alterations to the electrophysiology of isolated human detrusor smooth muscle
      cells in bladder disease.
AB  - The aim of the study was to investigate the properties of the inward calcium
      current (iCa) obtained from isolated human detrusor smooth muscle cells in
      different pathological conditions using the whole-cell patch-clamp technique.
      Previous experiments on field stimulated detrusor muscle strips have shown
      specific differences associated with hypertrophy and detrusor instability. As iCa
      plays an important role in excitation-contraction coupling in this tissue, it was
      therefore of interest to determine if iCa was altered in the above disease
      states. It was found that myocytes from patients with prostatic symptoms had a
      significantly increased surface area and that the kinetics of iCa were also
      significantly altered in these cells. Although the surface area of cells from
      patients with idiopathic instability and detrusor hyperreflexia was also
      significantly increased, the kinetics of iCa were altered in different ways.
      These alterations to iCa will alter the action potential configuration and its
      propagation through the muscle mass.

PMID- 8309001
TI  - Sensory modulation of the medial preoptic area neuronal activity by dorsal penile
      nerve stimulation in rats.
AB  - The study was aimed at finding out the influence exerted by the genital afferents
      on the medial preoptic area (mPOA), which plays a pivotal role in the regulation
      of male sex behavior. To fulfil this objective, the effects of stimulation of the
      dorsal penile nerve (DPN) on the activity of 82 mPOA neurons were studied. The
      base line firing rates of the mPOA neurons, studied by extracellular recording,
      ranged between 0.5 and 38.5 Hz (mean 7.18 +/- 7.91). The stimulation of the DPN
      (20 Hz, 0.4 msec. 70 microA) influenced 79.69% of the neurons studied. Though
      increased firing was the predominant influence produced (50%), decreased firing
      was also seen in a few (29.69%). The excited and inhibited neurons were randomly
      distributed within the mPOA. Neurons located in the lateral and posterior
      hypothalamus were not affected by the DPN stimulation. The stimulation parameters
      used in this study did not produce any change in the systemic arterial pressure
      and heart rate. The results provide electrophysiological evidence of afferent
      inputs from the male sex organ to the mPOA, which is an important area
      controlling male sex behavior.

PMID- 8309002
TI  - Localization of endothelin receptors in the human prostate.
AB  - The objective of the present study was to localize endothelin receptors in the
      human prostate using quantitative autoradiography. Slide-mounted tissue sections
      20 microns. in thickness were obtained from the transition zones of seven
      patients undergoing radical prostatectomies for low volume prostate cancer.
      Sarafotoxin (S6C) and BQ123 have been used to distinguish endothelin receptor
      subtypes (ETA and ETB). The prostatic tissue sections were incubated in four
      different stock solutions containing the following: 0.1 nM. 125I-endothelin-1
      (125I-ET-1) (total ET-1 binding); 0.1 nM. 125I-ET-1 and 100 nM. S6C (total ETA
      binding); 0.1 nM. 125I-ET-1 and 1 microM. BQ123 (total ETB binding); and 0.1 nM.
      125I-ET-1 and 1 microM. ET-1 (nonspecific ET-1 binding). Nonspecific binding
      accounted for only 12 and 15% of total 125I-ET-1 binding in the stroma and
      glandular epithelium. Autoradiograms were quantitatively analyzed using a
      computerized image analysis system. Specific radioactive densities (nCi/mg.) were
      determined for the stromal and glandular epithelial elements of the prostate. The
      specific radioactive densities of ETA and ETB binding sites in the stroma were
      7.57 +/- 0.65 and 2.98 +/- 0.81. The specific radioactive densities of ETA and
      ETB binding sites in the glandular epithelium were 1.59 +/- 0.15 and 7.87 +/-
      1.35. The present study demonstrates that the predominant endothelin receptors in
      the stroma and glandular epithelium are the ETA and ETB subtypes, respectively.

PMID- 8309003
TI  - Renal pathology and the 99mTc-DMSA image during the evolution of the early
      pyelonephritic scar: an experimental study.
AB  - This study describes the pathologic changes underlying the appearances of the
      99mTc-DMSA renal image during acute pyelonephritis induced in piglets by a
      combination of vesicoureteral reflux (VUR) and urinary infection. In a total of
      42 animals examined, pathologic lesions were identified in 36 of the 46 kidneys
      subjected to VUR and urinary infection, but no lesions developed in the remaining
      10 refluxing kidneys. While scintigraphic defects were invariably associated with
      pyelonephritic lesions (specificity 100%), some small lesions were not identified
      (sensitivity 80%). There was a significant association (p = < 0.001) between the
      degree of photon deficiency seen scintigraphically and the histologic changes
      (early and late lesions). However, the scintigraphic appearance of individual
      lesions was also influenced by factors such as their extent and density, so that
      consideration of the macroscopic characteristics was also important for precise
      correlation.

PMID- 8309004
TI  - Reduction in norepinephrine content of the rabbit urinary bladder by alpha-2
      adrenergic antagonist after electrical pelvic floor stimulation.
AB  - The present study was designed to obtain evidence of reflex activation of the
      hypogastric nerves during electrical pelvic floor stimulation. Rabbits were
      treated with yohimbine (900 micrograms./kg./min.) with and without electrical
      stimulation under general anesthesia. Norepinephrine (NE) content of the rabbit
      bladder body and base were estimated by high performance liquid chromatography.
      Administration of yohimbine alone reduced the NE content of the bladder base (p <
      0.05). The combination of yohimbine and electrical pelvic floor stimulation
      decreased NE content in the bladder base to a greater extent (p < 0.001); NE
      content in the bladder body decreased slightly (p < 0.001). Here we present
      evidence that the hypogastric nerves are reflexively activated by stimulation of
      the pelvic floor structures.

PMID- 8309005
TI  - Prosthetic bladder: in vivo studies on an active negative-pressure-driven device.
AB  - Active alloplastic bladders were implanted into four dogs after cystectomy and
      were well tolerated. The prosthesis created a vacuum of -90 cm. H2O in the upper
      tracts, which gradually decreased until the bladder filled. Renal function was
      maintained as long as the prostheses worked effectively. Hydronephrosis developed
      and renal function deteriorated if the bladder was not emptied, even though the
      leak pressure was only 3 to 5 cm. H2O. Both resolved when active bladder function
      was restored. Pressures in the ureter were measured percutaneously, at flow rates
      up to 15 ml. per minute (900 ml. per hour). At 15 ml. per minute, the pressure
      only reached a maximum of 16 cm. H2O. Encrustation did not occur even in the
      presence of infection. The results achieved with this negative pressure bladder
      prosthesis, which is emptied actively, are very promising and should provide the
      impetus for increased research in this field of urology.

PMID- 8309006
TI  - Urinary bladder dysfunction in the BB/W diabetic rat: effect of ganglioside
      treatment on functional and structural alterations.
AB  - Urinary bladder dysfunction in the diabetic BB/W rat is characterized by
      infrequent irregular contractions of high amplitude. Initially these occur in the
      absence of detectable neuroanatomical lesions of sensory afferent and
      parasympathetic fibers of the pelvic nerve, which constitute the micturition
      reflex arc. Structural lesions consisting of progressive axonal atrophy of
      myelinated and unmyelinated fibers become detectable only after 4 months of
      diabetes. In the current study we evaluated the effect of ganglioside treatment
      (10 mg./kg. body weight) for one month. This drug regimen was initiated at 4
      months of diabetes, when functional bladder abnormalities were well established,
      whereas structural lesions were yet to appear. Animals examined 1 or 3 months
      after termination of the one-month treatment protocol showed sustained
      normalization of the characteristic functional abnormalities, accompanied by
      prevention of the neuroanatomical lesions of sensory afferent and parasympathetic
      efferent myelinated fibers in the pelvic nerve. These data suggest that
      ganglioside treatment may be beneficial in delaying the progression of diabetic
      autonomic neuropathy in this experimental animal model.

PMID- 8309007
TI  - Potentiation of purinergic neurotransmission in guinea pig urinary bladder by
      histamine.
AB  - Patients suffering from the inflammatory condition of interstitial cystitis
      frequently exhibit an increased number of mast cells in the bladder. To determine
      whether mast cell mediators have the potential to influence the neurogenic
      contraction of the bladder smooth muscle and thereby possibly contribute to the
      symptoms of interstitial cystitis, we examined the effects of histamine, a major
      inflammatory mediator of mast cell origin, on nerve- and agonist-induced
      contractions of in vitro strips of guinea pig urinary bladder. Histamine (10
      microM.) potentiated by more than 50% the nerve-induced contraction of bladder
      strips evoked by field stimulation with 0.5 msec. pulses at 4 Hz. Because the
      neurogenic contraction of the bladder is mediated by at least two
      neurotransmitters, acetylcholine (ACh) and ATP, we examined the effects of
      histamine on each of these transmitters. Histamine potentiated responses to the
      purinergic component of the neurogenic response (that part of the neurogenic
      response that remains after treatment with atropine) and potentiated responses to
      exogenously applied ATP. Histamine did not potentiate the response to the
      cholinergic component of the neurogenic response (that part of the neurogenic
      response that remains after desensitization of purinoceptors with alpha, beta
      methylene ATP) nor responses to carbachol, a cholinergic agonist. These results
      indicate that histamine potentiates the neurogenic response of the bladder by
      influencing the purinergic component, apparently at postjunctional sites.

PMID- 8309008
TI  - Early antibody response following vasectomy is related to fertility after
      vasovasostomy in glucocorticoid-treated and untreated Lewis rats.
AB  - The influence of treatment with a glucocorticoid on antisperm antibodies and
      fertility after vasectomy and vasovasostomy was studied in Lewis rats. Animals
      received a bilateral vasectomy followed 4 weeks later by bilateral vasovasostomy.
      Treatment with methylprednisolone for two months beginning at the time of the
      vasovasostomy resulted in a decrease in antisperm antibodies compared with
      nontreated vasovasostomized animals, but there was no difference in fertility
      between treated and nontreated vasovasostomized groups. However, when fertile
      vasovasostomized animals from treated and nontreated groups were compared with
      infertile vasovasostomized animals, antisperm antibodies were found to be
      significantly lower in fertile rats 2, 4 and 8 weeks after vasectomy, while
      antibodies did not differ between fertile and infertile animals at the end of the
      study (12 weeks). The observation that differences in antisperm antibodies
      appeared shortly after vasectomy, preceding either vasovasostomy or treatment,
      suggests that changes occurring very early after vasectomy have far-reaching
      effects and are among the factors that influence future fertility after
      vasovasostomy.

PMID- 8309009
TI  - Effects of castration and exogenous testosterone supplementation in an animal
      model of penile erection.
AB  - The dependence of erectile behavior on androgen functioning is well established.
      Castration produces loss of both libido and potency in man and animals. The
      present study, using an animal model for potency, demonstrates the dependence of
      centrally induced erectile behavior on an intact androgen milieu. Castrated rats
      failed to produce an erection in response to apomorphine, an agent shown to
      produce erection in nearly all normal rats. Administration of exogenous
      testosterone propionate in dosages exceeding 60 micrograms./kg. produced a
      significant increase in erectile behavior. Yawning, an essentially parallel
      phenomenon to the stimulation of the erectile response, was also decreased
      following castration and responded similarly to increasing amounts of exogenous
      testosterone, demonstrating the influence of androgen functioning on the central
      nervous system. It was concluded that testosterone is a necessary prerequisite
      for the maintenance of a centrally induced erectile and yawning response. In an
      animal model of penile erection, testosterone increases the number of erections
      in a dose-dependent manner in castrated rats. The dependence of the erectile
      response on testosterone is, at least in part, centrally mediated.

PMID- 8309010
TI  - A piece of my mind. Hands on.

PMID- 8309011
TI  - AMA office directs smokeLess states.

PMID- 8309012
TI  - No lighting up in more workplaces, other sites.

PMID- 8309013
TI  - Smokers may pay, but not their own way.

PMID- 8309014
TI  - Tobacco control report card fails some Federal entities, gives all tough future
      assignments.

PMID- 8309016
TI  - Biotechnology industry calls for active US role.

PMID- 8309015
TI  - Canada reduces cigarette tax to fight smuggling.

PMID- 8309017
TI  - From the Health Care Financing Administration.

PMID- 8309018
TI  - From the Centers for Disease Control and Prevention. Reported vaccine-preventable
      diseases--United States, 1993, and the childhood immunization initiative.

PMID- 8309019
TI  - From the Centers for Disease Control and Prevention. Foodborne outbreaks of
      enterotoxigenic Escherichia coli--Rhode Island and New Hampshire, 1993.

PMID- 8309020
TI  - Actual causes of death in the United States.

PMID- 8309021
TI  - Actual causes of death in the United States.

PMID- 8309022
TI  - Actual causes of death in the United States.

PMID- 8309023
TI  - Actual causes of death in the United States.

PMID- 8309024
TI  - Is there a Gulf War syndrome?

PMID- 8309025
TI  - The predictive capabilities of clinical tests: the 6-minute walk.

PMID- 8309026
TI  - Optic and peripheral neuropathy in Cuba.

PMID- 8309027
TI  - Optic and peripheral neuropathy in Cuba.

PMID- 8309028
TI  - Optic and peripheral neuropathy in Cuba.

PMID- 8309029
TI  - A comparison of the efficacy and toxic effects of sustained- vs immediate-release
      niacin in hypercholesterolemic patients.
AB  - OBJECTIVE: To compare escalating doses of immediate-release (IR) and sustained
      release (SR) niacin for effectiveness in reducing levels of low-density
      lipoprotein cholesterol and triglycerides and increasing levels of high-density
      lipoprotein cholesterol, and for the occurrence of adverse reactions, especially
      hepatotoxicity. DESIGN: Randomized, double-blind, parallel comparison of IR and
      SR niacin administered sequentially at 500, 1000, 1500, 2000, and 3000 mg/d, each
      for 6 weeks. SETTING: Cholesterol research center. PATIENTS: Forty-six adults, 23
      in each group, with low-density lipoprotein cholesterol levels greater than 4.14
      mmol/L (160 mg/dL) after 1 month of a step 1 National Cholesterol Education
      Program diet. OUTCOME MEASURES: Fourteen-hour fasting lipid and lipoprotein
      cholesterol levels, results of clinical laboratory tests, a symptom
      questionnaire, and withdrawal rates. RESULTS: The SR niacin lowered low-density
      lipoprotein cholesterol levels significantly more than IR niacin did at the
      dosage of 1500 mg/d and above, while IR niacin increased high-density lipoprotein
      cholesterol levels significantly more than SR niacin did at all dosage levels.
      The reduction in triglyceride levels was similar with IR and SR niacin. Nine
      (39%) of the 23 patients assigned to the IR dosage form withdrew before
      completing the 3000-mg daily dose; the most common reasons for withdrawal were
      vasodilatory symptoms, fatigue, and acanthosis nigricans. Eighteen (78%) of the
      23 patients assigned to the SR dosage form withdrew before completing the 3000-mg
      daily dose; the most common reasons for withdrawal were gastrointestinal tract
      symptoms, fatigue, and increases in levels of liver aminotransferases, often with
      symptoms of hepatic dysfunction. None of the patients taking IR niacin developed
      hepatotoxic effects, while 12 (52%) of the 23 patients taking SR niacin did.
      CONCLUSION: The SR form of niacin is hepatotoxic and should be restricted from
      use. The IR niacin is preferred for the management of hypercholesterolemia but
      can also cause significant adverse effects and should be given only to patients
      who can be carefully monitored by experienced health professionals.

PMID- 8309030
TI  - Outcome of out-of-hospital cardiac arrest in New York City. The Pre-Hospital
      Arrest Survival Evaluation (PHASE) Study.
AB  - OBJECTIVE: To determine survival from out-of-hospital cardiac arrest in New York
      City and to compare this with other urban, suburban, and rural areas. DESIGN:
      Observational cohort study. SETTING: New York City. PARTICIPANTS: Consecutive out
      of-hospital cardiac arrests occurring between October 1, 1990, and April 1, 1991.
      INTERVENTION: Trained paramedics performed immediate postarrest interviews with
      care providers, using a standardized questionnaire. MAIN OUTCOME MEASURES: Entry
      criteria, elapsed time intervals, and nodal events conformed to Utstein
      recommendations. The single target end point was death or discharge home.
      RESULTS: Of 3243 consecutive cardiac arrests on which resuscitation was
      attempted, 2329 (72%) met entry criteria as primary cardiac events. Overall
      survival was 1.4% (99% confidence interval [CI], 0.9% to 2.3%). No patients were
      lost to follow-up. Survival from witnessed ventricular fibrillation was 5.3% (99%
      CI, 2.9% to 8.8%). Using survival from witnessed ventricular fibrillation for
      intersystem comparison, our survival rate was similar to that of Chicago, Ill
      (4.0%; 99% CI, 1.9% to 7.5%; P = .41), the only other large city on which data
      were available. However, it was significantly lower than that reported from
      midsized urban/suburban areas (33.0%; 99% CI, 30.4% to 35.6%; P < .0001) and
      suburban/rural areas (12.6%; 99% CI, 8.9% to 16.3%; P < .0001). Survival rate
      among arrests occurring after arrival of emergency medical services personnel
      (8.5%; 99% CI, 4.7% to 14.0%) was comparable with Chicago (6.6%; 99% CI, 3.3% to
      11.5%; P = .41) but markedly lower than King County, Washington (36%; 99% CI,
      28.6% to 43.8%; P < .0001). CONCLUSIONS: Survival from out-of-hospital cardiac
      arrest in New York City was poor. This was partly attributable to lengthy elapsed
      time intervals at every step in the chain of survival. However, examination of
      survival among arrests occurring after emergency medical services arrival
      suggests that other features may predispose residents of large cities to higher
      cardiac arrest mortality than individuals living in more suburban or rural
      settings. Since half the US population resides in large metropolitan areas, this
      represents a public health problem of considerable magnitude.

PMID- 8309031
TI  - Physicians' behavior and their interactions with drug companies. A controlled
      study of physicians who requested additions to a hospital drug formulary.
AB  - OBJECTIVE: It is controversial whether physicians' interactions with drug
      companies affect their behavior. To test the null hypothesis, that such
      interactions are not associated with physician behavior, we studied one behavior:
      requesting that a drug be added to a hospital formulary. DESIGN: Nested case
      control study. SETTING: University hospital. PARTICIPANTS: Full-time attending
      physicians. Case physicians were all 40 physicians who requested a formulary
      addition from January 1989 through October 1990. Control physicians were 80
      randomly selected physicians who had not made requests. MAIN EXPOSURE MEASURE:
      Physician interactions with drug companies, as determined by survey of physicians
      (response rate, 88% [105/120]). RESULTS: Physicians who had requested that drugs
      be added to the formulary interacted with drug companies more often than other
      physicians; for example, they were more likely to have accepted money from
      companies to attend or speak at educational symposia or to perform research (odds
      ratio [OR], 5.1; 95% confidence interval [CI], 2.0 to 13.2). Furthermore,
      physicians were more likely than other physicians to have requested that drugs
      manufactured by specific companies be added to the formulary if they had met with
      pharmaceutical representatives from those companies (OR, 13.2; 95% CI, 4.8 to
      36.3) or had accepted money from those companies (OR, 19.2; 95% CI, 2.3 to
      156.9). These associations were consistent in multivariable analyses controlling
      for potentially confounding factors. Moreover, physicians were more likely to
      have requested formulary additions made by the companies whose pharmaceutical
      representatives they had met (OR, 4.9; 95% CI, 3.2 to 7.4) or from whom they had
      accepted money (OR, 1.7; 95% CI, 1.0 to 2.7) than they were to have requested
      drugs made by other companies. CONCLUSION: Requests by physicians that drugs be
      added to a hospital formulary were strongly and specifically associated with the
      physicians' interactions with the companies manufacturing the drugs.

PMID- 8309032
TI  - Culture and clinical care. Folk illness beliefs and behaviors and their
      implications for health care delivery.
AB  - This article presents an approach to the evaluation of patient-held beliefs and
      behaviors that may not be concordant with those of biomedicine. Physicians and
      patients often hold discrepant models of health and illness that may affect the
      effectiveness of communication during the clinical visit. An extreme example of
      such a discrepancy exists when the patient feels that he or she has an illness
      that is not defined within the biomedical paradigm. These are commonly referred
      to as folk illnesses. An example of such an illness is provided in order to
      discuss the effects of folk beliefs on patient-held perceptions of health and
      sickness, treatment-seeking behavior, clinical care, and physician-patient
      communication. Guidelines for addressing clinical issues surrounding folk beliefs
      and behaviors in a culturally sensitive way are discussed.

PMID- 8309033
TI  - A cluster of invasive pneumococcal disease in young children in child care.
AB  - OBJECTIVE: To investigate a cluster of invasive pneumococcal disease in children
      8 to 26 months of age, using standard microbiological procedures and ribosomal
      DNA gene-restriction patterns to characterize the outbreak strain. DESIGN:
      Outbreak investigation. SETTING: A family child-care home with six children in
      Baltimore, Md. RESULTS: During an 8-day period, three of the six children in the
      family child-care home had febrile illnesses with pneumococcal bacteremia, and a
      fourth had purulent pneumococcal conjunctivitis. Type 12F Streptococcus
      pneumoniae was isolated from the four ill children and from the nasopharynges of
      the two healthy children. Ribotyping revealed all outbreak isolates had an
      identical ribotype pattern. Administration of rifampin to the children did not
      eradicate carriage of the organism. CONCLUSIONS: Our data demonstrate that child
      care provides an opportunity for outbreak of invasive pneumococcal disease in
      young children. This observation suggests a need for increased alertness for
      clusters of pneumococcal disease in young children in child-care facilities and
      underscores the necessity for a pneumococcal vaccine that is effective in infants
      and young children.

PMID- 8309034
TI  - Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the
      published literature.
AB  - OBJECTIVE: To quantify the efficacy of BCG vaccine against tuberculosis (TB).
      DATA SOURCES: MEDLINE with index terms BCG vaccine, tuberculosis, and human.
      Experts from the Centers for Disease Control and Prevention and the World Health
      Organization, among others, provided lists of all known studies. STUDY SELECTION:
      A total of 1264 articles or abstracts were reviewed for details on BCG
      vaccination, concurrent vaccinated and unvaccinated groups, and TB outcome; 70
      articles were reviewed in depth for method of vaccine allocation used to create
      comparable groups, equal surveillance and follow-up for recipient and concurrent
      control groups, and outcome measures of TB cases and/or deaths. Fourteen
      prospective trials and 12 case-control studies were included in the analysis.
      DATA EXTRACTION: We recorded study design, age range of study population, number
      of patients enrolled, efficacy of vaccine, and items to assess the potential for
      bias in study design and diagnosis. At least two readers independently extracted
      data and evaluated validity. DATA SYNTHESIS: The relative risk (RR) or odds ratio
      (OR) of TB provided the measure of vaccine efficacy that we analyzed. The
      protective effect was then computed by 1-RR or 1-OR. A random-effects model
      estimated a weighted average RR or OR from those provided by the trials or case
      control studies. In the trials, the RR of TB was 0.49 (95% confidence interval
      [CI], 0.34 to 0.70) for vaccine recipients compared with nonrecipients
      (protective effect of 51%). In the case-control studies, the OR for TB was 0.50
      (95% CI, 0.39 to 0.64), or a 50% protective effect. Seven trials reporting
      tuberculous deaths showed a protective effect from BCG vaccine of 71% (RR, 0.29;
      95% CI, 0.16 to 0.53), and five studies reporting on meningitis showed a
      protective effect from BCG vaccine of 64% (OR, 0.36; 95% CI, 0.18 to 0.70).
      Geographic latitude of the study site and study validity score explained 66% of
      the heterogeneity among trials in a random-effects regression model. CONCLUSION:
      On average, BCG vaccine significantly reduces the risk of TB by 50%. Protection
      is observed across many populations, study designs, and forms of TB. Age at
      vaccination did not enhance predictiveness of BCG efficacy. Protection against
      tuberculous death, meningitis, and disseminated disease is higher than for total
      TB cases, although this result may reflect reduced error in disease
      classification rather than greater BCG efficacy.

PMID- 8309035
TI  - Users' guides to the medical literature. III. How to use an article about a
      diagnostic test. B. What are the results and will they help me in caring for my
      patients? The Evidence-Based Medicine Working Group.

PMID- 8309036
TI  - Failure of tuberculosis control. A prescription for change.

PMID- 8309037
TI  - Over-the-counter niacin.

PMID- 8309038
TI  - The importance of taking a sensitive sexual history.

PMID- 8309039
TI  - The experience of gay and lesbian students in medical school.

PMID- 8309040
TI  - [Clinical evaluation of diazepam suppository for premedication in children].
AB  - Anesthesiologists need a safe and effective premedication before general
      anesthesia and want to help decrease anxiety and minimize psychologic trauma to
      children. Therefore, we evaluated diazepam suppository (0.5 mg.kg-1 body weight)
      administered to 21 children before minor surgery under general anesthesia. We
      evaluated the sedative effect of the diazepam suppository (tablet) on the arrival
      at the operating room, during anesthesia induction and in the recovery room. On
      the arrival at operating room, 86% of children were sedated, and 65% of children
      could be induced smoothly under mask. There was no delayed emergence. Plasma
      diazepam level at induction was 376.5 +/- 28.4 ng.ml-1, which is the level needed
      for sedation. We conclude that diazepam suppository is a useful drug for
      premedication in children.

PMID- 8309041
TI  - [Intranasal midazolam for sedation before anesthesia in pediatric patients].
AB  - To evaluate the efficacy of nasally administered midazolam for sedation before
      anesthesia in pediatric patients, the authors studied 45 ASA PS 1 or 2 patients
      (aged 9 months-6 years) scheduled for elective surgery. The sedative effect of
      intranasal midazolam (0.2 mg.kg-1 or 0.3 mg.kg-1) was compared with that of our
      standard premedication by score. Significant sedative effect was obtained 4 min
      (in the 0.2 mg.kg-1 group) and 3 min (in the 0.3 mg.kg-1 group) after nasal
      administration. Most patients (93%) in the midazolam group became either free
      from anxiety or calm allowing easy separation from the parents and a smooth
      induction of anesthesia 10 min after nasal administration. There was no
      respiratory depression or anesthetic complication during induction of anesthesia,
      and no delayed recovery was observed. These results indicate that intranasal
      midazolam 0.2 mg.kg-1 is an effective and useful method for rapid sedation of
      children just prior to the induction of anesthesia.

PMID- 8309042
TI  - [Anesthetic management for emergency operation in seven patients with gunshot
      injury].
AB  - Seven patients with gunshot injury underwent emergency operations under general
      anesthesia. Trachea was intubated without muscle relaxants or after crash
      induction. Anesthesia was maintained with intravenous or volatile anesthetic
      agents titrated slowly. Four of seven patients fell into hypovolemic shock and
      were treated with aggressive intravenous volume replacement, vasopressors and
      catecholamines. Seven patients were given blood transfusion, of which the largest
      amount given was 17700 ml during the operation. Hemopneumothorax occurred in four
      patients, who needed intrathoracic drainage. Six patients survived and one died
      of multiple organ failure secondary to hypovolemic shock. The nature and severity
      of a bullet wound depend on the characteristics of the bullet (mass,
      construction, tendency to fragment or yaw, and velocity) and the tissue through
      which it has traveled. Therefore, the wound is often larger than expected, and
      the bullet may travel in an unexpected direction. Thus, it is important in
      anesthetic management of a patient with gunshot injury, to understand its
      mechanisms and evaluate the wound and to treat the patients in the same way as
      with other multiple trauma, especially taking care of hypovolemic shock.

PMID- 8309043
TI  - [Anesthetic management of a patient with abdominal aortic aneurysm (AAA) with
      giant bulla].
AB  - We report a case of abdominal aortic aneurysm with giant bulla in a 58-year-old
      man who had an elective abdominal aortic reconstruction surgery. Preoperative
      chest x-ray showed a giant bulla in the right lung and small bullae in the left.
      General anesthesia was induced with midazolam 0.5 mg, fentanyl 0.2 mg and
      succinylcholine chloride 80 mg. After tracheal intubation, anesthesia was
      maintained under spontaneous breathing with halothane 0.5-1% in a mixture of air
      and oxygen (FIO2 0.4-1.0) supplemented with continuous epidural mepivacaine from
      the catheter inserted the day before surgery. Since satisfactory analgesia and
      muscle relaxation were achieved by epidural mepivacaine, no analgesics and muscle
      relaxants were administered during the operation. Postoperatively, no
      complications occurred and the patient was extubated and transferred to the
      intensive care unit. We emphasize that combined epidural and light general
      anesthesia with spontaneous respiration might be ideal for the safe anesthetic
      management of a patient with a giant bulla.

PMID- 8309044
TI  - [A case of elevated serum creatine-kinase after anesthesia].
AB  - An elevation of creatine-kinase was noted postoperatively in a 50 year-old male
      who had cerebral aneurysm surgery under isoflurane, N2O and O2 anesthesia. Serum
      CK concentration reached as high as 5919 IU.l-1 immediately after surgery and
      elevation was associated with the temperature elevation of above 39.5 degrees C
      and port-wine urine. The postoperative course was uneventful and elevated serum
      creatine-kinase was corrected within next 6 days. Since elevated serum creatine
      kinase is known to occur in acute stage of cerebrovascular accident, and since
      the influence of myocardial infarction, malignant hyperthermia and drugs could be
      neglected, we assumed that an abnormal elevation of CK values observed in the
      present patient resulted from stimulation of sympathetic nervous system due to
      cerebral bleeding and to hyperpermeability of sarcolemma of skeletal muscle.

PMID- 8309045
TI  - [Anesthesia for the intraoperative electrocorticography of patients with
      uncontrollable epilepsy].
AB  - For the surgical treatment of uncontrollable epilepsy, it is essential to
      delineate the epileptogenic focus by the use of intraoperative
      electrocorticography. Most general anesthetic agents, however, suppress the
      epileptogenic focus. Therefore, such a patient is usually kept awake during the
      procedure using local anesthesia. We experienced 15 cases for these procedures.
      Anesthesia was induced with thiamylal and pancuronium was administered for
      tracheal intubation. Anesthesia was maintained with nitrous oxide, oxygen and
      enflurane or isoflurane. After the brain was exposed, volatile anesthetics were
      discontinued and replaced with intermittent fentanyl administration.
      Approximately 15 minutes before the start of intraoperative electrocorticography,
      nitrous oxide concentration was reduced to 30% or less. A resective epileptogenic
      focus was identified in every patients. In 2 patients, electrocorticographical
      focal seizure status was identified following the intraoperative
      electrocorticography. After the focus resection, seizure attacks were controlled
      only by the application of regular medical regimen in these patients. Low nitrous
      oxide and intermittent fentanyl administration can be recommended as a superior
      anesthesia technique for intraoperative electrocorticography.

PMID- 8309046
TI  - [A patient with hepatoma and hepatic cirrhosis showing abnormally high blood
      morphine concentration after periodical suppository administration].
AB  - Morphine hydrochloride 10 mg suppository was given every 6 hours in a patient
      with hepatoma and hepatic cirrhosis. The serum morphine concentration increased
      continuously until 4 hours after the second administration, and peak level showed
      17 ng.ml-1. Morphine-6-glucuronide and morphine-3-glucuronide in the serum
      persisted at low levels of 32.4 ng.ml-1 and 169 ng.ml-1 respectively. Three days
      after the administration, morphine suppository had to be discontinued because of
      severe nausea and vomiting. It should be noticed that a remarkable reduction in
      morphine metabolism may occur and this may lead to unexpected high serum
      concentration of morphine in a patient with hepatic dysfunction.

PMID- 8309047
TI  - [Microcirculatory disturbances in normotensive stage of endotoxin shock].
AB  - Red blood cell (RBC) deformability is necessary for maintenance of normal
      oxygenation in microcirculation. To evaluate oxygen utilization in the early
      stage of endotoxin shock, we observed RBCs from a rheological point of view in
      mesenteric microcirculation in rats. Endotoxin shock was induced by Shwaltzman
      reaction. The velocity of RBC decreased from 1.33 mm.sec-1 to 0.55 mm.sec-1 at 60
      min after the provoking injection. RBC could not change its shape in capillaries.
      In contrast, the mean blood pressure remained at 110 mmHg throughout this
      observation. In hemorrhagic shock the deformability of RBC in capillaries was not
      impaired even though mean blood pressure decreased to 43 mmHg. In vitro, we
      examined the index of RBC deformability with or without endotoxin by the modified
      Reid's method. The index was decreased significantly by endotoxin. We conclude
      that impaired deformability of RBC may be a factor of insufficient oxygen
      utilization in the early stage of endotoxin shock.

PMID- 8309048
TI  - [Anesthesiological management of a patient with primary aldosteronism complicated
      with hypertrophic cardiomyopathy].
AB  - A 49-year-old male with primary aldosteronism, accompanied by hypertrophic
      cardiomyopathy (HCM), underwent our anesthesiological management for resection of
      a left adrenal tumor. The preoperative examination revealed hypertension, mild
      nephropathy and hypokalemia. Spilnolactone treatment was discontinued 3 days
      before surgery. In the operating room, a Swan-Ganz catheter was inserted for
      monitoring hemodynamic parameters. Anesthesia was maintained with nitrous oxide
      oxygen-isoflurane and vecuronium. During the surgery, prostaglandin E1 and
      nitroglycerin were used as vasodilators. During surgery, the patient was
      successfully managed, anesthesiologically. In anesthesiological management of
      patients with primary aldosteronism, care is needed regarding changes in blood
      pressure and electolyte levels during adrenalectomy. In cases where aldosteronism
      is accompanied by HCM, as in the present case, hemodynamic changes can cause a
      fatal outcome, and hence, carefulness is needed in using anesthetics and drugs
      which act on the circulatory system.

PMID- 8309050
TI  - [Usefulness of the interchangeable medical bibliography: introduction of
      "reference transform utility" program for Macintosh].
AB  - We made a text file format exchange program on HyperCard 2.0 for medical
      bibliography. Some database applications on Macintosh to manage the medical
      bibliography were available. FileMaker ProJ, EndNotePlus and Microsoft Excel were
      well known as popular databases and spread sheet application for Macintosh. The
      data format among the applications is not uniform. We need to translate a data
      format into another format to share the same data among these database
      applications. But it requires a lot of time and labor to make this conversion by
      manual operation. We have developed a file conversion utility program with
      HyperCard as a user friendly software.

PMID- 8309049
TI  - [A new neuromuscular transmission monitor (TOF Guard): the rationale behind the
      method and its clinical usefulness].
AB  - TOF Guard is one of the latest developments in the field of neuromuscular
      monitoring equipment. This system uses a miniature acceleration transducer (a
      piezo-electric ceramic wafer is used), simply fastened to the thumb with tape.
      The rationale behind the method is Newton's second law, stating that the
      acceleration is directly proportional to the force. In this study, authors
      assessed the accuracy of this system in clinical use, comparing with the force
      transducer method (Myograph 2000). The result showed that there was a very close
      positive correlation between the values of T1, TOF ratio and posttetanic count
      simultaneously measured by both methods. The coefficient of correlation was 0.96,
      and its significance level was P < 0.001. From the clinical view point, it is
      concluded that TOF Guard is very useful because of its accuracy and because the
      equipment is easy to handle, compact and of low price as a neuromuscular
      monitoring system for routine anesthesia.

PMID- 8309051
TI  - [The effect of endotoxin on the neutrophil chemiluminescence in the rabbit].
AB  - To examine the effects of endotoxin on the neutrophil function, neutrophil
      dependent microbicidal activities were evaluated by the chemiluminescence (CL)
      method in rabbits injected with endotoxin. Six rabbits in the first group were
      administered saline intravenously as control. Ten rabbits each in the second and
      third group received endotoxin 0.7 microgram.kg-1 and 70 micrograms.kg-1
      respectively. Luminol-dependent CL in whole blood (whole blood CL) and in
      isolated neutrophils (neutrophil CL) were examined before administration and 30,
      60, 180 and 360 min after administration. Peak values of whole blood CL in the
      second group were significantly depressed at 30 and 60 min, and elevated at 360
      min. Those in the third group were depressed more than in the second group at all
      times after endotoxin administration. Peak values of neutrophil CL in the second
      group at 180 and 360 min were significantly elevated, but those in the third
      group at 30, 60, 180 min were markedly depressed. Experiments combining
      neutrophils and pooled plasma revealed that these CL responses were associated
      with the neutrophils themselves. It is speculated that the neutrophil suppression
      observed in the third group was caused by the overactivation of neutrophils
      induced by the activated complements and some other stimulating factors, and/or
      may be due to the abundant appearance of immature granulocytes with lesser
      activities.

PMID- 8309052
TI  - [The effect of the posture in the spread of the epidural anesthesia].
AB  - In 20 gynecological patients, the radionuclide was injected through the epidural
      catheter to determine the effect of the posture on the distribution of the
      radionuclide in the epidural space. Each 5 were placed on supine, right
      decubitus, left decubitus or sitting position and the posture was maintained for
      30 min after the injection of the radionuclide. The distribution of the
      radionuclide in the epidural space was determined by measurement of gamma ray by
      a gamma camera. The data were stored and analyzed by a digital computer
      (SINTIPAC). In supine and right decubitus position, the radionuclide was
      distributed more on the right side and in the left decubitus position the
      radionuclide was distributed evenly. In the sitting position the radionuclide was
      distributed more caudad and the cephalad distribution was limited compared to the
      other postures. In summary the solution in the epidural space may move by the
      gravity but these effects were very slight and are of only minor clinical
      significance.

PMID- 8309053
TI  - [Arterial ketone body ratio and its modification by PGE1 in elderly patients
      during gastrectomy].
AB  - We evaluated the change in arterial ketone body ratio (AKBR), which is a
      parameter to indicate the liver cells, during gastrectomy, and effect of PGE1 on
      its change in the elderly patients, compared with the younger patients. Twenty
      patients studied were elderly (above 65 years) and twenty were younger (below 60
      years). PGE1 was administered in 10 elderly and 10 younger patients, and the
      remainders did not receive PGE1. Decrease in AKBR during the resection of stomach
      and immediate increase in AKBR after the resection of stomach were observed in
      younger patients. On the other hand, prolonged decrease in AKBR after the
      resection of stomach was observed in elderly patients. Administration of PGE1
      accelerated the restoration of AKBR after the resection of the stomach in elderly
      patients and caused an increase in AKBR during the resection of stomach in
      younger patients. These findings suggest that hepatic functional capacity in
      elderly patients is less than that in younger patients, and that administration
      of PGE1 has a protective effect on liver in both elderly and younger patients.

PMID- 8309055
TI  - [The effects of fresh gas flow rate on the work of breathing during semi-closed
      circuit anesthesia].
AB  - To evaluate the effects of fresh gas flow rate on the work of breathing during
      semi-closed circuit anesthesia, we measured respiratory frequency, tidal volume,
      inspiratory work of breathing, peak inspiratory and expiratory flow rate and
      fluctuations in airway pressure during breathing with fresh gas flow of 6 l.min
      1, 3 l.min-1 and 1.5 l.min-1. There was no significant difference among three
      flow rates in terms of tidal volume, respiratory frequency, inspiratory work of
      breathing, peak inspiratory flow rate and fluctuation in airway pressure at
      inspiration. On the other hand, in the expiratory phase, peak expiratory flow
      rate was lower and fluctuation in airway pressure at expiration was higher at 6
      l.min-1 than those at 3 l.min-1 and 1.5 l.min-1, which may be indicative of
      increased expiratory work of breathing. The present study shows that low fresh
      gas flow rate does not increase the inspiratory work of breathing and high fresh
      gas flow rate may increase the expiratory work of breathing, implying that
      lowering the fresh gas flow is profitable for the work of breathing during semi
      closed circuit anesthesia.

PMID- 8309054
TI  - [Alteration of lipid peroxidation and the activity of peroxide metabolism enzymes
      in the liver, kidney and lung following the administration of paraquat in mice].
AB  - The sequential changes of the activity of peroxide metabolism enzymes and
      thiobarbituric acid reaction substance (TBARS) as an indicator of lipid peroxide
      concentration were observed to analyze the mechanisms of tissue injury due to the
      administration of paraquat in DDY mice. Each six mice were decapitated at 3, 6,
      9, 12, 15, 18, 21 or 24 hours following the intraperitoneal administration of
      paraquat 60 mg.kg-1, and the liver, kidney and lung were removed and homogenized
      to quantify lipid peroxide concentration and the activity of peroxide metabolism
      enzymes. In the liver and kidney, TBARS increased gradually and reached the
      maximum level at 9 hours after the administration of paraquat in the liver and at
      12 hours in the kidney. Significant increases in superoxide dismutase (SOD),
      glutathione peroxidase and catalase (CAT) activities were observed at 15 or 18
      hours after the injection of paraquat. In the lung, lipid peroxide concentration
      decreased significantly and the activities of SOD and CAT increased at 15 hours
      after injection of paraquat. TBARS in serum started to increase at 9 hours after
      the administration of paraquat and reached the maximum level at 15 hours. These
      findings indicate that the induction of peroxide metabolism enzymes followed the
      increase of TBARS which was induced by paraquat in the liver and kidney. However,
      the enzyme induction was produced by paraquat without the increase of TBARS in
      the lung. Active oxygen radicals play an important role in the toxic action of
      paraquat and might produce the induction of peroxide metabolism enzymes following
      the administration of paraquat.

PMID- 8309057
TI  - [The effects of intrathecal clonidine in spontaneously hypertensive rats].
AB  - The relationship between intrathecal clonidine and hypertension was investigated
      in SHR rat and WKY rat. After the animals were given clonidine 15 micrograms into
      the lumbar intrathecal space, blood pressure, heart rate and respiratory rate
      were recorded for 60 minutes under nembutal anesthesia. Percent change of mean
      blood pressure was significantly larger in SHR rat than in WKY rat at 50 and 60
      minutes after clonidine injection. No difference was observed in percent change
      of heart rate and respiratory rate. The results suggest the possibility that
      lumbar intrathecal clonidine injection produces greater hypotension in
      hypertensive subjects than in normotensive subjects.

PMID- 8309056
TI  - [Effect of 10% carbon dioxide on regional myocardial tissue oxygen tension and
      myocardial metabolism].
AB  - We investigated the effects of arterial carbon dioxide tension on myocardial
      blood flow, tissue oxygen tension and metabolism in the anesthetized dogs.
      Eighteen adult mongrel dogs weighing 13.4 +/- 3.6 kg were anesthetized with 0.5%
      isoflurane, intubated and ventilated mechanically with 50% oxygen to maintain
      normocapnia. Endtidal CO2 fraction (FECO2) was monitored continuously by
      capnograph. Regional myocardial tissue PO2 was measured using a monopolar
      polarographic needle electrode inserted to the myocardium. Electromagnetic blood
      flow probes were applied on the left anterior descending artery and circumflex
      artery. For cardiac venous blood sampling, a 23G intravenous catheter was
      inserted into the cardiac veins (great coronary veins) carefully. After
      normocapnic ventilation, hypocapnia was induced by increasing the respiratory
      rate, and hypercapnia was induced by adding 10% carbon dioxide to the inspired
      gas. The coronary blood flow and myocardial tissue oxygen tension increased
      during hypercapnia and the myocardial lactate extraction decreased, while excess
      lactate and cardiac venous L/P ratio increased during hypercapnia. These results
      indicate that hypercapnia increase coronary flow and myocardial tissue oxygen
      tension but myocardial aerobic metabolism is impaired during hypercapnia.

PMID- 8309058
TI  - [Increased [3H] PN 200-110 binding sites in the myocardial sarcolemmal membrane
      in endotoxin shock rats].
AB  - To study the effects of endotoxin shock on calcium channels of sarcolemma, we
      investigated the characteristics of binding of a radioligand, [3H] PN 200-110
      (PN), to relatively pure sarcolemmal membrane (SL) from the heart of endotoxin
      shock rats. The rats were induced into endotoxin shock with the cecal ligation
      and puncture. The SL of the early group (EG), in hyperdynamic stage, was isolated
      from the rat's heart, 9 hours after the procedure, and that of late group (LG),
      in hypodynamic stage, was isolated from the rat's heart, 18 hours after the
      procedure. Binding of PN to SL of EG was 31-37% greater than to SL of the sham
      operated rat (CG), while binding of PN to SL of LG was not raised significantly,
      as compared to that to CG. The maximum number of PN binding sites (Bmax) was 35%
      higher in SL of EG than in SL of CG, but there was no significant difference
      between Bmax in SL of LG and CG. On the other hand, the affinity for PN binding
      (KD) was similar in all three groups. Since PN binding sites are considered to be
      specific sites for the voltage-dependent Ca2+ channels of sarcolemma, it is
      concluded that the density of these channels in the sarcolemma of rat increases
      during the early stage of endotoxin shock and decreases to control level in the
      late stage of the shock.

PMID- 8309059
TI  - [Comparative study of 20% marine salt and 20% NaCl on circulatory dynamics during
      hemorrhagic shock in dogs].
AB  - This study was conducted to investigate the effect of 20% marine salt as compared
      with 20% NaCl solution, on the circulatory dynamics in hemorrhagic shock using
      mongrel dogs. Ten mongrel dogs were randomly divided into two groups. One treated
      with 20% marine salt, and the other treated with 20% NaCl. Modified Wigger's
      method was used to induce hemorrhagic shock. Hypotension was kept at 45 mmHg for
      45 minutes and then 1.5 ml.kg-1 of 20% marine salt or 20% NaCl was injected
      intravenously in bolus. Twenty percent marine salt reduced total peripheral
      resistance and increased cardiac output with statistically significant difference
      compared with 20% NaCl. There were increases in MAP, PAP and PWP without
      statistic differences between the two groups. These results suggest that 20%
      marine salt, including various trace elements, is superior to 20% NaCl in
      improving cardiac output and TPR during hemorrhagic shock.

PMID- 8309060
TI  - [Effects of ulinastatin on extravascular lung water volume in patients undergoing
      cardiopulmonary bypass].
AB  - Pulmonary dysfunction often follows cardiopulmonary bypass (CPB). In the present
      study, we examined (1) the effects of the human urinary tripsin inhibitor
      ulinastatin on the extravascular lung water volume (EVLW), and (2) A-aDO2 as an
      indicator of pulmonary function, in 30 adult patients undergoing CPB. We
      administered 600,000 U of ulinastatin intravenously immediately before start of
      CPB in 15 patients (U group). In the control group without ulinastatin,
      remarkable transient increases in EVLW and A-aDO2 occurred after CPB. In
      contrast, in the U group extravascular lung water volume level was maintained
      within the normal range and an inhibited transient increase in A-aDO2 after CPB
      was observed. We conclude that the administration of ulinastatin in patients
      undergoing CPB may be useful to prevent pulmonary dysfunction following CPB.

PMID- 8309061
TI  - [Inhibitory effect of fentanyl citrate on endothelium-dependent relaxation in rat
      aorta].
AB  - We studied the effect of fentanyl on the endothelium-dependent vascular responses
      in isolated rat aortic strips. Fentanyl depressed the endothelium-dependent
      relaxation induced by acetylcholine but not that induced by the calcium
      ionophore, A23187. Endothelium-independent relaxation in response to sodium
      nitroprusside (SNP), a soluble guanylate cyclase activator, was not depressed by
      fentanyl. On the other hand, fentanyl depressed the increase in cyclic GMP level
      stimulated by acetylcholine but not that stimulated by A23187 or SNP.
      Furthermore, fentanyl depressed the vasocontraction by acetylcholine but not that
      by histamine or KCl in isolated pig coronary artery strips without endothelium,
      suggesting that fentanyl can inhibit endothelium-independent contraction via
      muscarinic receptor on smooth muscle cells. These results suggest that fentanyl
      can inhibit endothelium-dependent vasorelaxation via endothelium-derived relaxing
      factor (EDRF) by acting on endothelial cells but not on smooth muscle cells. The
      inhibitory effect of fentanyl on the relaxation probably occurs at the level of
      muscarinic receptor on endothelial cells or at a site before biochemical pathways
      converting L-arginine to EDRF.

PMID- 8309062
TI  - [The effect of wound perfusion on the relief of postoperative pain].
AB  - The efficacy of wound perfusion (WP) with lidocaine for postoperative pain relief
      was studied in patients with median incision for cholecystectomy. Twenty four
      patients were divided into 3 groups according to the method of postoperative pain
      relief; group C, n = 8: intramuscular injections of penta-zocine 30 mg
      administered on demand, group WP, n = 8: WP with continuous lidocaine perfusion
      for 24 hours (plus pentazocine on demand); group EPI, n = 8: buprenorphine
      administered epidurally for 24 hours (plus pentazocine on demand). Pain scores at
      0, 6, 12, 24, 48, hours after operation were examined. Arterial blood gas
      analysis, FVC and FEV1 were measured preoperatively and on the first
      postoperative day. Pain scores at 0 and 24 hours in group WP and EPI were
      significantly lower than those in group C. There were no significant differences
      in the scores between group WP and EPI at all the points. Analgesic requirement
      was significantly reduced in group WP and EPI compared with group C. FVC, FEV1
      and PaO2 were significantly reduced postoperatively in every group but there were
      no differences among three groups. PaCO2 significantly increased postoperatively
      in group C and EPI. We conclude that the technique of wound perfusion with
      lidocaine is effective and safe for postoperative pain relief.

PMID- 8309063
TI  - [Laboratory and clinical evaluation of S-1108 in pediatric field].
AB  - We performed laboratory and clinical evaluation of S-1108 granules, a new oral
      cephalosporin antibiotic, in the pediatric field. 1. Pharmacokinetics of S-1108
      was examined with 6 patients, at a dose of 4 mg/kg that was orally ingested 30
      minutes after meal. Mean plasma concentrations at 30 minutes, 1, 2, 4, 6 and 8
      hours after dose were 0.35, 0.63, 0.86, 0.75, 0.37 and 0.09 microgram/ml,
      respectively, with a half life of 1.14 hours. The urinary recovery rate in the
      first 8 hours was 25.5%. 2. The clinical efficacy of S-1108 was evaluated in 31
      patients with various infectious diseases. S-1108 was administered at doses
      ranging 2 to 4.2 mg/kg/dosage, 3 times a day for 1/3 to 10 days. Clinical effects
      were excellent in 19, good in 12, with an efficacy rate of 100%.
      Bacteriologically, all causative organisms except two of Staphylococcus aureus
      and Haemophilus influenzae were eradicated, with an eradication rate of 80%. As
      an adverse reaction, mild diarrhea was noted in 2 patients. Slight elevations of
      GOT and/or GPT were noted in 2 patients. Only 1 child had difficulty ingesting
      the antibiotic preparation. From the above results, we have concluded that S-1108
      is a highly effective and safe for patients with various infectious diseases in
      the pediatric fields.

PMID- 8309064
TI  - [Clinical studies on S-1108 in the field pediatrics].
AB  - Clinical studies on S-1108, a new oral cephem antibiotic, were carried out in the
      field of pediatrics. The following results were obtained. 1. The peak plasma
      level of S-1006 when administered after meal at a dose of 4 mg/kg was 2.47
      micrograms/ml at an hour, and the serum half-life was 0.81 hour. The 4 hours
      urinary excretion rate of S-1006 was 35.7%. 2. S-1108 was administered to 15
      children with various infections (3 patients with pneumonia, 3 with acute
      bronchitis, 4 with scarlet fever, 2 with acute tonsillitis, 1 with phlegmon and 2
      with urinary tract infections). The overall clinical efficacy rate was 100%. 3.
      Side effects or abnormal laboratory test values were not observed except for
      diarrhea in 1 and eosinophilia in 1.

PMID- 8309065
TI  - [Clinical evaluation of S-1108 in children].
AB  - We administered S-1108 to 16 children with ages ranging from 7 month to 15 years
      at doses between 1.8 and 6.0 mg/kg x 3/day for 3 to 13 days. We evaluated the
      efficacy and safety of S-1108 in 11 children with respiratory tract infections, 3
      urinary tract infections, and 2 skin infections. The efficacy rate of S-1108 was
      100% and bacteriological eradication rate was 83.3%. No adverse effects were
      observed. These results suggested that S-1108 could be used safely in children.

PMID- 8309066
TI  - [Clinical study on S-1108 in treatment of pediatric infections].
AB  - To evaluate the efficacy, the safety and the usefulness of a novel and esterified
      cephem antibiotic for oral use, S-1108, in pediatric infections, a clinical trial
      was performed. The study subjects were 15 patients including 9 with acute
      pharyngitis, 1 with acute tonsillitis, 2 with acute bronchitis, 1 with chronic
      pyelonephritis, 1 with acute abscess of the skin and 1 with impetigo contagiosa.
      S-1108 was administered orally at a dose of 3.7 mg/kg to 12.5 mg/kg t.i.d. for 4
      to 9 days. Clinical effects were excellent in 7 cases, good in 6, fair in 1 and
      poor in 1. The Overall efficacy rate was 86.7%. Bacteriologically, causative
      organisms were all eradicated in evaluable 4 cases. As to side effects, diarrhea
      was observed in 2 cases. No abnormal laboratory test values were obtained.

PMID- 8309067
TI  - [Clinical evaluation of S-1108 in pediatric field].
AB  - Nine pediatric patients with bacterial infections (5 cases of tonsillitis, 3
      cases of impetigo and 1 case of UTI) were treated with S-1108, and the efficacy
      and the safety were evaluated. The clinical responses to S-1108 treatment were
      excellent in 7 cases and good in 2. The efficacy rate was 100%.
      Bacteriologically, the causative organisms (Streptococcus pyogenes,
      Staphylococcus aureus, Haemophilus parainfluenzae and Escherichia coli) were
      eradicated. No clinical side effects were observed. Elevation of CK in 2 cases
      and eosinophilia in 1 case were noted.

PMID- 8309068
TI  - [Criteria for the clinical evaluation of antifungal drugs in pediatrics].

PMID- 8309069
TI  - [Bacteriological evaluation of combined effects of vancomycin and beta-lactams.
      I. Results against methicillin-resistant Staphylococcus aureus].
AB  - We previously reported a part of the results we obtained regarding
      antibacteriological synergism between beta-lactams and vancomycin (VCM) against
      methicillin-resistant Staphylococcus aureus (MRSA). This paper reports an
      additional assessment we made subsequently to the previous report regarding
      antibacterial effects of different beta-lactams and VCM concurrently used against
      MRSA. Assessed in this study were bacteriological synergistic actions between
      flomoxef (FMOX) and VCM, latamoxef (LMOX) and VCM, cefpirome (CPR) and VCM and
      imipenem (IPM) and VCM against MRSA. 1. Synergistic enhancements of therapeutic
      activities were observed against MRSA with FMOX +VCM, CPR + VCM and IPM + VCM,
      but the activity of LMOX + VCM was low. 2. Concentration dependencies of actions
      of these antibiotic agents against MRSA were strong for beta-lactams, but weak
      for VCM. These observations were opposite of the results for beta-lactams and
      aminoglycosides, or beta-lactams and tetracyclines against MRSA we reported
      previously. 3. It appeared that strong synergistic antibacterial effects were
      obtained with FMOX or CPR concentrations between 8 and 32 micrograms/ml when used
      with VCM, and IPM concentrations between 4 and 16 micrograms/ml when used with
      VCM, hence, in the therapy using these combinations, concentrations and dose
      intervals of beta-lactams employed should be carefully considered. 4. When these
      antibiotics are used together in in vitro experiments, values of MIC and FIC
      index may be different depending upon experimental systems used.

PMID- 8309070
TI  - [Bacteriological evaluation of combined effects of vancomycin and beta-lactams.
      II. Results against gram-negative rods].
AB  - Evaluations were made for antibacterial activities of combination uses of
      flomoxef (FMOX) + vancomycin (VCM) against clinically isolated bacteria of family
      Enterobacteriaceae, and latamoxef (LMOX) + VCM, cefpirome (CPR) + VCM, and
      imipenem (IPM) + VCM against also clinically isolated Pseudomonas aeruginosa. The
      obtained results are summarized as follows. 1. FMOX and VCM appeared to act
      independently against Enterobacteriaceae without showing synergism or antagonism.
      2. Regarding antibacterial effects of LMOX + VCM, or CPR + VCM against P.
      aeruginosa strains, MIC values under the combined uses were approximately 1
      dilution (2 folds) higher than LMOX or CPR used alone, but we did not consider
      that these results meant the presence of antagonism between the beta-lactams and
      VCM. 3. Experimental results suggested that an antagonistic relationship was
      present between IPM and VCM against P. aeruginosa. The degree of the antagonism
      was dependent on VCM concentrations. In other words, when VCM is present at a
      concentration between 4 and 128 micrograms/ml, MIC values for IPM increased 2 to
      4 dilutions (4 to 16 folds), whereas in the presence of 1 to 2 micrograms/ml VCM,
      MIC values for IPM were close to those of IPM alone. Further, some of this
      tendency was observed for FMOX against bacteria of family Enterobacteriaceae in
      the presence of VCM. 4. These results suggest that the dose level of VCM should
      be considered based on a low range when a combination therapy is considered
      between beta-lactams and VCM in the treatment of infections with MRSA alone or
      with Gram-negative rods with MRSA.

PMID- 8309071
TI  - [Pharmacokinetic, bacteriological and clinical studies on S-1108 in children].
AB  - Pharmacokinetic, bacteriological and clinical studies on S-1108 were performed in
      children. The results were as follows: 1. A total of 11 patients were treated
      with S-1108. Each dose was 3 mg/kg, orally administered 3 times daily for 4-14
      days. The clinical efficacies of S-1108 in 10 patients with bacterial infections
      (1 with bacteremia, 4 with pneumonia, 1 with acute maxillary sinusitis, 1 with
      scarlet fever and 2 with streptococcal pharyngitis) were evaluated as excellent
      in 8 patients and as good in 2 patients with an efficacy rate of 100%. Only one
      patient with staphylococcal scalded skin syndrome due to methicillin resistant
      Staphylococcus aureus (MRSA) who received gamma-globulin was not evaluated.
      Fourteen causative strains of 5 species were found in 10 patients. Three strains
      of Streptococcus pneumoniae out of 5, 2 of 3 Branhamella catarrhalis strains,
      none of Staphylococcus aureus and all 3 strains of Streptococcus pyogenes were
      eradicated. No adverse reaction was observed in any of the 11 patients. 2. MICs
      of S-1108 against 5 clinically isolated S. pneumoniae from cases of infections
      were examined. All of them were relatively highly resistant to penicillins. S
      1108 was compared with cefteram pivoxil, cefpodoxime proxetil, cefaclor and
      cefixime, and it showed better antibacterial activity or than other cephems. 3.
      Double peaks were obtained in plasma levels of S-1108 orally administered at a
      dose of 3 mg/kg at 30 minutes after meal and were 1.03 microgram/ml and 0.74
      microgram/ml at 1 and 4 hours after administration, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8309072
TI  - [Clinical evaluation of S-1108 in children].
AB  - A new oral cephem antibiotic, S-1108, was evaluated for its clinical efficacy and
      safety in children. S-1108 was effective in 95% of the 59 examined cases of
      respiratory, middle ear, skin and urinary tract infections. S-1108 was highly
      effective in infections of Streptococcus pyogenes, Haemophilus influenzae and
      Escherichia coli, but was less effective in penicillin-resistant Streptococcus
      pneumoniae and Staphylococcus aureus infections. The serum half-life was 1.26 +/-
      0.36 hours upon after meal administration of 4 mg/kg. No severe adverse reaction
      was encountered. From these data, S-1108 appears to be safe and effective in
      children with susceptible bacterial infections.

PMID- 8309073
TI  - [Laboratory and clinical studies on S-1108 in the pediatric field].
AB  - Laboratory and Clinical Studies on S-1108, a new oral cephem antibiotic, were
      carried out to evaluate its usefulness at a dose between 2 and 4 mg/kg a day for
      7 to 14 days in the pediatric field. 1) Pharmacokinetic studies S-1108 at a dose
      of 2 mg/kg was administered to evaluate the pharmacokinetic parameters in 1
      subject. Cmax, T1/2 and AUC were 0.69 hour, 1.42 hours and 2.15 micrograms.hr/ml,
      respectively. 2) Antimicrobial activities MICs against various clinically
      isolated organisms (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus
      pneumoniae, Branhamella catarrhalis, Escherichia coli and Haemophilus influenzae)
      were determined. The MIC values of S-1006 were similar to those of cefteram, the
      MICs against S. pyogenes, and H. influenzae were < or = 0.025 and 0.10
      microgram/ml, respectively. 3) Clinical studies S-1108 was administered to
      patients with various pediatrics infections in 34 cases (upper respiratory tract
      infections: 12 cases, lower respiratory tract infections: 5 cases, urinary tract
      infections: 9 cases, skin and soft tissue infection: 6 cases, otitis media: 2
      cases). Clinical efficacy rate was evaluated according to "Standard of clinical
      evaluation in pediatrics field". The responses were all good or excellent. 4)
      Side reactions There were no serious adverse reactions in any cases. The above
      results suggest that S-1108 is potent effective and safe agent in the pediatric
      field at a dose between 2-4 mg/kg (t.i.d.) a day.

PMID- 8309074
TI  - [Studies on S-1108 in pediatric infection].
AB  - Pharmacokinetic and clinical studies on S-1108, a new oral cephem antibiotic,
      were performed in pediatric infections and the following results were obtained.
      1. Pharmacokinetics studies Pharmacokinetics of S-1108 was studied in 4 children
      (3 y 7 m-11 y 1 m) using doses of 2 mg/kg (n = 2) and 4 mg/kg (n = 2). The
      average peak plasma level was 0.88 microgram/ml at 2 hours after administration
      of 2 mg/kg and 2.00 micrograms/ml at 3 hours after administration of 4 mg/kg, and
      plasma half-lives were 1.45 and 0.96 hours, respectively. Average cumulative
      urinary recovery rates at 0-6 hours were 30.0 and 34.8%, respectively. 2.
      Clinical studies S-1108 was administered to 32 patients with various infectious
      diseases (6 with acute tonsillitis, 2 each with pertussis and acute bronchitis, 3
      with pneumonia, 4 with scarlet fever, 5 with impetigo contagiosa, 6 with acute
      urinary infection and 1 each with subcutaneous abscess, impetigo, vulvitis and
      urethritis) at daily doses between 6-12 mg/kg/day, t.i.d., for 5-12 days.
      Clinical responses were excellent in 17 patients, good in 13, and poor in 2, and
      the efficacy rate was 93.8%. Bacteria were identified and 33 strains of 12
      species were found. The eradication rate was 93.9%. No side effects were observed
      in 43 patients. Abnormal laboratory test values were observed in 2 patients, 1
      with elevation of eosin. and the other with elevations of GOT and GPT. The
      results suggest that S-1108 may be a very useful and safe drug for the treatment
      of pediatric infections.

PMID- 8309075
TI  - [Pharmacokinetic and clinical studies of S-1108 in the pediatric field].
AB  - Pharmacokinetic and clinical studies on S-1108, a new oral cephem antibiotic,
      were performed in the field pediatrics. The following results were obtained. 1)
      Antibacterial activities Antibacterial activities of S-1006, the active form of S
      1108, were studied against clinically isolated strains of (Staphylococcus aureus
      (n = 5), Streptococcus pneumoniae (n = 6), Streptococcus pyogenes (n = 3),
      Haemophilus influenzae (n = 8), Branhamella catarrhalis (n = 5) and Haemophilus
      parainfluenzae (n = 2). MIC values ranged < or = 0.025-1.56 for GPC and < or =
      0.025-0.78 microgram/ml for GNR. 2) Absorption and excretion Blood concentrations
      and urinary excretion rates of S-1108 were measured upon administration of S-1108
      after meal at dose of 3 mg/kg (n = 4), 4 mg/kg (n = 1) and 6 mg/kg (n = 1). The
      peak blood concentrations of S-1006 at a dose of 3 mg/kg (n = 4), ranged from
      0.57 to 1.82 micrograms/ml at 1, 2 and 4 hours after dosing. Mean pharmacokinetic
      parameters T1/2 and AUC were 1.29 +/- 0.69 hours and 4.47 +/- 2.25
      micrograms.hr/ml, respectively. At a dose of 4 mg/kg and 6 mg/kg, peak
      concentrations were 1.79 and 1.27 micrograms/ml at 2 and 3 hours after treatment.
      T1/2 and AUC were 1.34 and 1.11 hours, and 8.19 and 5.65 micrograms.hr/ml,
      respectively. Urinary recovery rates ranged from 13.0 to 37.2% for the first 8
      hours after administration. 3) Clinical studies Clinical efficacies were examined
      in 32 cases of various pediatric infections including 5 cases of acute pneumonia,
      11 cases of bronchitis, 2 cases of scarlet fever, 8 cases of tonsillitis, 1 case
      of pharyngitis, 2 cases of otitis media and 3 cases of UTI. Clinical efficacy
      rate was 96.9% (31/32) and bacteriological eradication rate was 87.1% (27/31).
      There were no side effects and abnormal laboratory test values except 1 case
      (Eosino. 2-->10%) in the 32 cases.

PMID- 8309076
TI  - [Microbiological and immunological studies on mycobacteria, especially on the
      biologic activities of BCG.DNA].

PMID- 8309077
TI  - [Molecular genetic studies on virulence-associated chromosomal loci of Shigella
      flexneri 2 a].

PMID- 8309078
TI  - [Clinical evaluation of endoscopic variceal ligation (EVL)].
AB  - From August 1992 through February 1993, we treated 21 patients with endoscopic
      variceal ligation (EVL). Two patients had a history of the esophageal variceal
      bleeding, but 19 patients did not have bleeding episodes. To evaluate preventive
      effect of bleeding, we selected the patients who had grade F2 or red color sign
      positive varices. We repeated EVL until varices improved into grade F0 or F1 and
      red color sign negative. The therapeutic goal was sometimes changed according to
      patient's general condition. No additional therapy was performed to eradicate
      varices, such as endoscopic injection sclerotherapy. As a result of our therapy,
      eradication rate was 73.7% and period of hospitalization were 25 +/- 11 days. No
      major complications were found during and after EVL. EVL affected neither liver
      function test nor size of gastric varices. Recurrent varices with red color sign
      were found in 4 patients, but easily controlled by retreatment with EVL. EVL
      seems to be convenient and effective therapy in our short-term study, and useful
      for preventive therapy of the esophageal variceal bleeding.

PMID- 8309079
TI  - [A case of cystadenocarcinoma of the liver assessed by MRI before surgical
      operation].

PMID- 8309080
TI  - [A case of hepatic lipoma].

PMID- 8309081
TI  - [Three cases of tumorous necrotic lesion of the liver].

PMID- 8309082
TI  - [A case of hepatic artery aneurysm ruptured into the biliary tract to be treated
      with hepatic artery embolization].

PMID- 8309083
TI  - [A case of sarcoidosis presenting paracholedochal lymph nodes swelling].

PMID- 8309084
TI  - [Crohn's disease accompanied with pancreatitis. A report of a case].

PMID- 8309085
TI  - [Forms of an in vivo polymerization product, n-butyl-2-cyanoacrylate, within the
      gastric wall].
AB  - The in vivo morphology of sclerosants, n-butyl-2-cyanoacrylate (Histoacryl;
      referred hereinafter to briefly as HA) polymer formed within the gastric wall was
      investigated in an animal experiment. The results indicate that HA polymer formed
      after local injection of HA into the stomach wall with deliberate avoidance of
      contact with blood got scattered in an arboroid pattern, suggesting thus that
      when HA is injected into the gastric mucosa at an extravascular site, the
      resulting polymer is likely to get scattered and miss the target site.
      Polymerization products that were formed after injection of HA alone were deep
      purple, dense, firm, rounded in shape and lesser in adverse histologic influence
      upon the walls of stomach. On the other hand, those formed by injection of HA
      with Lipiodol were large-sized, light brown and oval-shaped ones with more
      irregular margins and less distinct boundaries as compared to those seen after
      injection of HA alone. These results of the study led us to conclude that at the
      present time it would seem wise to limit the use of HA for this particular
      therapeutic purpose only to those cases of bleeding gastric varices.

PMID- 8309086
TI  - [Evaluation of the mechanism of endothelin-induced rat gastric mucosal lesion
      formation].
AB  - There are several reports on the gastric mucotoxic effect of endothelin (ET). The
      mechanism of this effect, however, remains largely unknown. To evaluate this, we
      assessed the gastric injury and changes in gastric mucosal blood flow induced by
      ET using ONO-1078, a sulfide peptide leukotriene (LT) antagonist, CV-3988, a
      platelet-activating factor (PAF) antagonist, and diltiazem, a Ca2+ channel
      blocker. In fasted and anesthetized rats, 2 nmol/kg of ET was infused for 30 min
      into splenic artery to deliver the drug as much as selectively to the stomach.
      Ninety minutes after beginning the drug infusion rats were killed and gastric
      mucosal damage in the removed stomachs was assessed. Gastric mucosal blood flow
      (GMBF) was measured for 90 min with a 30 min-interval by the laser Doppler
      flowmetry method. ET induced severe gastric mucosal damage, which was
      characterized by congestion of mucosal capillary and accompanied by significant
      reduction of GMBF, as compared with control. However, these mucotoxic effect of
      ET was significantly inhibited by 20 mg/kg of ONO-1078 given i. g. 60 min before
      ET infusion and i. v. administration of 10 mg/kg of CV-3988 and 1 mg/kg of
      diltiazem 30 min prior to ET. From these results, we conclude that PAF, LT and
      Ca2+ may play important pathogenetic roles as chemical mediators in the mechanism
      of the formation of ET-induced gastric mucosal lesions.

PMID- 8309087
TI  - [Functional anomaly of the duodenal papilla].

PMID- 8309088
TI  - [Evaluation of colon diseases by using new method of extracorporeal ultrasonic
      examination during usual colon endoscopy].
AB  - Generally two types of ultrasonic colon examination method are carried out. One
      is extracorporeal ultrasonographic examination (US). And another is endoscopic
      ultrasonographic examination (EUS). US is technically easy but is difficult to
      take good image of colon diseases. EUS can give us good and sufficient
      informations. But it is technically difficult and gives much trouble to patients.
      During usual endoscopy, we have tried extracorporeal ultrasonic examination by
      filling de-aired water around the diseased colon area. With this new method, we
      could easily identify the disease and got much better picture than usual US. And
      this new method gave almost no trouble and pain to examinees in comparison with
      EUS.

PMID- 8309089
TI  - [Manometric study of the biliary sphincter zone: a comparison between the length
      of phasic activity and the narrow distal segment].
AB  - Motor activity of the sphincter of Oddi has been evaluated in 26 patients who
      underwent ERCP examination. Manometric recordings from the common bile duct and
      the sphincter of Oddi were performed with a single end-lumen perfused catheter.
      The number of successive 3 mm spaced black marks, observed during the pull
      through from the first appearance of the proximal sphincter activity to that of
      duodenal pressure, was used to measure the length of the sphincter zone. In 14 of
      26 patients, the length of phasic activity zone of the sphincter of Oddi was 9
      mm. However, the narrow distal segment of the common bile duct was 15.1 +/- 3.6
      mm in length. In same patients, the length of phasic activity zone was shorter
      than the anatomical one. The mean sphincter of Oddi pressure (SOP) at the
      distance of 6 mm from the papillary pore (77.8 +/- 22.1 mmHg) was greater than
      that of 9 mm (58.4 +/- 27.0 mmHg) and 12 mm (51.0 +/- 16.9 mmHg). These results
      suggest that the location of the orifice of catheter should be taken into
      consideration when comparing the SOP.

PMID- 8309090
TI  - [The effect of cholecystectomy on cellular proliferation of colonic mucosa in
      mice].
AB  - The relationship between cholecystectomy and colonic cancer has been suggested.
      The effect of cholecystectomy on cell proliferation of colonic mucosa in mice was
      studied immunohistochemically using bromodeoxyuridine (BrdU) and anti-BrdU
      monoclonal antibody after sham operation and cholecystectomy. In addition, the
      effect of carcinogen 1,2-dimethylhydrazine (DMH), on cellular proliferation of
      colonic mucosa was following. The results were obtained, (1) Cellular
      proliferation of colonic mucosa was increased after cholecystectomy. It was
      suggested that cholecystectomy influenced to the cellular proliferation of
      colonic mucosa in the study without carcinogen. (2) In the study using DMH, cell
      proliferation of colonic mucosa was increased after cholecystectomy. (3) At the
      time for the increased effect of DMH, cholecystectomy group tended to induce
      earlier proliferative effect than sham operation group.

PMID- 8309091
TI  - [Clinical evaluation of choledochoduodenal fistula near the duodenal papilla:
      association with separate openings of the pancreatic and biliary ducts].
AB  - A total of 1293 patients who underwent ERCP between 1980 and 1990 were reviewed.
      A parapapillary choledochoduodenal fistula (PCDF) was noted in 42 patients
      (3.2%). In order to study the frequency of PCDF, the patients were divided into
      groups of age of ten years. As a result, PCDF was formed to increase with advance
      in age. Thus the dispose is regarded as a "later on" disease. Thirty-one of these
      patients were included in the definite PCDF group, in which the distance between
      the papillar and fistulous opening was confirmed by cannulation or
      choledochography, and 11 in the questionable PCDF group, in which the distance
      was not confirmed, and thus the opening might be the separate openings of the
      pancreatic and biliary ducts (Mehnen's type I). The frequency of pneumobilia,
      biliary stone, history of cholecystectomy, biliary inflammation and obstruction
      were similar in the two groups. Only one patient suspected of having separate
      openings of the pancreatic and biliary ducts except the questionable PCDF was
      seen over the same period. This suggests that majority of the cases of separate
      openings of the pancreatic and biliary ducts, whose prevalence is estimated to be
      2-4% in Japan, may be PCDF.

PMID- 8309092
TI  - [Mucin-producing tumor of the pancreas: surgery or follow-up?].
AB  - Clinicopathological studies were carried out in 35 cases of mucin-producing tumor
      of the pancreas. In addition, natural history and serial pancreatogram changes
      were studied in 12 long-term follow-up cases. 83% of the main duct type and
      branch duct type greater than 4 cm were malignant, whereas hyperplasia cases were
      found in the branch duct type of 3 cm or less in size without marked dilation of
      the main duct and excrescent nodules. 33% of carcinoma cases were accompanied by
      parenchymal invasion and all those cases were of polypoid type of 2.5 cm or more
      in size. In long-term follow-up cases, all 3 cases of the main duct type showed
      progression of pancreatograms. In contrast, 8 of 9 cases of the branch duct type
      remained unchanged. These results suggest that surgical resection is mandatory in
      the main duct type and that the branch duct type where hyperplasia is highly
      suspected can be followed up.

PMID- 8309093
TI  - [A case of carcinosarcoma of the stomach].

PMID- 8309094
TI  - [A case of synchronous early gastric cancer and gallbladder adenosquamous
      carcinoma].

PMID- 8309095
TI  - [Crohn's disease in siblings].

PMID- 8309096
TI  - [Two cases of ischemic colitis in teenagers without underlying disease].

PMID- 8309097
TI  - [Sex identification of forensic biological materials].
AB  - The progress of sex identification methods for forensic biological materials such
      as dried bloodstains and others is reviewed on the basis of results obtained in
      our laboratory. Barr and Bertram (1949) discovered sexual dimorphism of mammalian
      interphase nuclei based on the presence of sex chromatin in the female and its
      absence in the male and also recognized a similar sex difference in human cells.
      Davidson and Smith (1954) first demonstrated sexual dimorphism in the
      polymorphonuclear leucocytes in the peripheral blood in man based on the presence
      of drumstick in the female and its absence in the male. Dixon and Torr (1956)
      first utilized the sex chromatin in the female nucleus to determine the sex from
      forensic materials. Matsumoto (1959, 1960) described a method to identify the sex
      from dried bloodstains by detecting drumstick. In general, however, the use of
      drumstick for the sex determination from dried bloodstains is very difficult
      because of a low frequency of drumstick itself and deformities of leucocyte
      nuclei in the stains by drying. Late in 1971, we introduced a method for
      detecting Y chromatin in the interphase nuclei of human male by fluorescent
      microscopy as a new tool for decisive male sex determination from forensic
      materials. This method was accepted as the reliable means to identify sex in
      forensic medicine. Since 1980, we have studied to identify sex from bloodstains
      by the ratio of sex hormones, testosterone and progesterone, determined by
      radioimmunoassay (RIA). We also examined the method of Witt and Erickson (1989)
      to detect Y and X chromosome specific DNA sequences using the polymerase chain
      reaction (PCR), and we improved this technique to exhibit its ability to identify
      sex from forensic materials. Our improved PCR method is thought to have a broad
      applicability to forensic practice because of its simplicity, sensitivity and
      reliability.

PMID- 8309098
TI  - [Relationship between postmortem change and biological reaction].
AB  - In the adipocere which is one of postmortem changes, some specific fatty acids
      possessing higher melting points together with soap play an important role in the
      formation of adipocere. These fatty acids were clarified to be mainly 10
      hydroxystearic and 10-hydroxypalmitic acids. Moreover, slight amounts of 10
      oxostearic and 10-oxopalmitic acids, which have higher melting points than those
      of hydroxy fatty acids, exist in the adipocere as well. The substantial adipocere
      is formed and stabilized by these specific fatty acids together with the soap.
      The hydroxy fatty acid (OHFA) and oxo fatty acid (OXOFA) are biosynthesized by
      some enzymes from bacteria. Various aerobic and anaerobic bacteria are involved
      in the formation of adipocere. For example, microbial conversion of various
      unsaturated fatty acids to 10-OHFA by Micrococcus luteus was investigated. As a
      result, 10-OHFA was synthesized only from fatty acids possessing cis-9
      unsaturation. It was also clarified that 10-OHFAs were converted to the
      corresponding 10-OXOFAs but the 10-OXO compounds were inactive as substrates.
      Furthermore, the enzyme preparations from Flavobacterium meningosepticum
      solubilized by sonication catalyzed not only hydration of oleic acid to produce
      10-hydroxystearic acid but also dehydrogenation of this product in the presence
      of deuterium. On the other hand, we found out that there was 10-hydroxy-12
      octadecenoic acid (10-OHLA) from linoleic acid in some kinds of adipocere. 10
      OHFA existing in adipocere has been thought not to exist in a living body.
      However, recently 10-epoxy-12-octadecenoic acid (leukotoxin, LTx) which is one of
      lipid peroxides was found not only in rice plants but in polymorphonuclear
      leukocytes. It was also clarified that these polymorphonuclear leukocytes
      produced the same 10-OHLA as the compound found in adipocere. Since LTx was found
      from leukocytes related to inflammatory response, it has been interested in
      involvement of not only the basic mechanism of biological defense but also the
      mechanism of shock as a vasoactive substance. A postmortem change itself is
      little associated with a phenomenon on a living body. However, 10-OHLA found in
      adipocere existed also in polymorphonuclear leukocytes, suggesting that this
      compound metabolized from LTx is closely related to a biological reaction.

PMID- 8309099
TI  - [Medico-legal studies on detection of organ-specific antigens].
AB  - When the organs have been injured, specific antigens pertaining to the organs
      could be expected to be released into the circulation and/or adhere to the
      weapons which has inflicted the damage to the organs. We could thus be able to
      identify the injured organs, if we could detect the antigens specific to the
      organs in blood of the victim and/or in bloodstains left on the weapons. 1. Liver
      specific antigen (LSA). The liver-specific antigen (LSA) was purified from the
      human liver and was showed to have a molecular mass of 52 kDa and pI of 5.8-5.9.
      Anti-human LSA antibody only reacted with the liver extract using immuno-dot
      blotting technique, and depending on the immunohistochemistry, this antigen was
      located within the cytoplasm of hepatocytes. The human LSA was proved to be a
      novel protein, isolated from the human liver, by the NH2-terminal amino acid
      sequence analysis. Anti-human LSA Fab'-peroxidase conjugate was prepared and a
      highly sensitive and specific sandwich enzyme immunoassay for human LSA was
      developed. The detection limit of this assay was 0.52 pg/tube. The LSA levels in
      the serum and blood of cadavers with liver injuries were markedly increased.
      These findings suggest that the human LSA will become a useful marker for
      detecting liver injury. 2. Sucrase-Isomaltase (SI). A sandwich enzyme immunoassay
      for SI, a dimeric digestive enzyme, was developed using pig as a model animal.
      SDS-solubilized proteins from the small intestine contained at least 50-fold
      larger SI than those from the other organs. Significant amount of SI could be
      detected in small intestinal contents and in stains left on the knife which had
      been stabbed into the small intestine. These results suggested that SI was a
      possible forensic marker for small intestinal injuries, although human SI
      remained to be examined. 3. Cardiac Troponin I (cTnI). The purpose of our study
      is to identify injuries to the heart from a small amount of blood quickly and
      accurately by using a sensitive enzyme immunoassay for cardiac troponin I (cTnI),
      a heart specific protein. Accordingly we purified cTnI from bovine cardiac muscle
      and prepared the antibody against cTnI in order to develop this assay. We
      furthermore investigated the usefulness of this antibody by immuno-dot-blotting.
      As the result, it was confirmed that this antibody reacted against only heart. 4.
      Dystrophin. The purpose of this work is to develop a method to determine skeletal
      muscle injuries using muscle-specific substances. Dystrophin was purified from
      SDS-solubilized bovine skeletal muscle.

PMID- 8309100
TI  - [Organ transplantation and inspection from medico-legal aspects].

PMID- 8309101
TI  - [Sex determination with a discriminant function analysis of deciduous teeth size
      in plaster models].
AB  - Plaster models of the teeth of 3-year-old Japanese children (96 males, 98
      females) were used to record the crown length, crown width and crown thickness of
      5 maxillary and 5 mandibular deciduous teeth (30 measurement values). These
      measurements were used to devise a number of sex determination formulae. A sex
      determination formula using all 30 values was calculated. Furthermore, a number
      of practical formulae were derived from only the crown width and crown thickness
      values because the deciduous teeth wear in 4 years and older children rapidly
      progress, making the crown length measurement unreliable. These formulae were
      calculated for the maxillary teeth alone and mandibular teeth alone. The formulae
      based on only the crown width or thickness were also calculated for both
      maxillary and the mandibular teeth. A step-wise discriminant analysis was then
      used to ascertain the most reliable measurements and a practical formula
      subsequently devised. The results obtained were as follows: 1. The mean value for
      each measurement was greater in males than in females. 2. Significant differences
      in the values recorded were seen in 28 out of the 30 measurements taken. The
      measurement items not exhibiting these significant differences were the crown
      width of the maxillary lateral incisor and the crown thickness of the mandibular
      second molar. 3. The accuracy rates for the sex-determination analysis and the
      step-wise sex determination analysis calculated using all 30 values were 78.6%
      and 75.7%, respectively. 4. The accuracy ranges for the modified sex
      determination formulae and the associated step-wise sex determination analyses
      were 70.6-78.4% and 67.0-76.8%, respectively.

PMID- 8309102
TI  - [ABO genotyping by polymerase chain reaction (PCR) and its application to
      paternity testing].
AB  - The authors describe the usefulness of ABO genotyping by polymerase chain
      reaction (PCR) in paternity testing. Blood samples were obtained from 80
      unrelated Japanese (20 samples in each of phenotypes of the ABO blood group
      system) and 13 cases of disputed paternity. PCR amplification of DNA extracted
      from blood by a conventional extraction procedure was carried out using the
      primers (primer 1: CACCGTGGAAGGATGTCCTC; primer 2: AATGTCCACAGTCACTCGCC; primer
      3: TGGAGATCCTGACTCCGCTG; primer 4: GTAGAAATCGCCCTCGTCCTT) described by Lee and
      Chang (J Forensic Sci, Vol. 37). The amplified DNA products using primer 1 and 2
      and the amplified DNA products using primer 3 and 4 were digested with Kpn I and
      Alu I, respectively. The amplified and digested DNA products were then analysed
      by electrophoresis on polyacrylamide gels. The bands on gels stained with
      ethidium bromide were observed with UV light and with silver staining. In 20
      samples of phenotype A, genotype AA was recognized in five samples and the others
      were genotype AO. In 20 samples of phenotype B, three samples were genotype BB
      and the others were genotype BO. According to this procedure, genotypes of
      phenotype AB and O were clearly and consistently confirmed. In 13 cases of
      disputed paternity, the paternity of six cases was excluded with some of red
      cell, serum protein, enzyme genetic markers and HLA systems except ABO phenotype.
      However, the paternity of three cases out of these six cases was excluded with
      ABO genotype. This study seems to support the usefulness of ABO genotyping by PCR
      in paternity testing.

PMID- 8309103
TI  - [Two unusual cases of half-sibling test with DNA polymorphism].
AB  - In usual paternity cases, the putative man and the mother-child couple are alive.
      However, there are some cases in which putative man and mother were deceased and
      only children were available for analyses. It is difficult to determine the
      presence or absence of half-sibling relationship from analyses of conventional
      blood group markers (CBGM). In this study, five kinds of single locus DNA probes
      were applied to 2 half-sibling cases. To decide usefulness of single locus DNA
      probes, we defined likelihood ratio of half-sibling (LRHS) based on the
      likelihood ratio of paternity (LRP) and also investigated the distribution curves
      of log10 LRHS in cases of unrelated combinations and half-sibling combinations.
      Distribution curves of log10 LRHS from DNA analyses in the cases of unrelated
      combinations and half-sibling combinations is more clearly separated than from
      CBGM. Single locus DNA probes are considered to be more informative for half
      sibling cases.

PMID- 8309104
TI  - [Paternity test by DNA fingerprinting in a sexual assault].
AB  - We have applied the method of DNA fingerprinting to resolve a paternity case. DNA
      samples were extracted from the blood of mother, child (4 months old fetus) and
      alleged father, digested with the restriction endonuclease Hinf I and Hae III,
      size separated by agarose gel electrophoresis, and hybridized with the multi
      locus minisatellite probe B.E.S.T.-MZ1.3 digoxigenin. DNA fingerprinting patterns
      in the child and alleged father indicated possibly paternity. Following
      extraction of DNA from cord blood (infant of 26 to 39 week's gestation), the
      quantity of DNA isolated was determined on a spectrophotometer at 260 nm and its
      integrity by electrophoresis in agarose gels. We found that high-molecular-weight
      DNA could be recovered in large quantities from cord blood as well as from adult
      blood.

PMID- 8309105
TI  - [Simultaneous assessment of exercise-induced abnormalities in myocardial
      perfusion and regional wall motion by using 99mTc-tetrofosmin].
AB  - To clarify the usefulness of the combined assessment of exercise (EX)-induced
      abnormalities in myocardial perfusion and regional wall motion for detecting
      coronary artery disease (CAD), we carried out first-pass radionuclide angiography
      and myocardial perfusion imaging during EX and at rest by 99mTc-tetrofosmin.
      Twenty-four patients with angiographically proven CAD, 9 (Gp A) with single and
      15 (Gp B) with multivessel disease, were studied. The sensitivity for the
      detection of CAD was 78% of Gp A, 73% of Gp B in planar image and 78%, 87% in
      SPECT image, respectively. When left ventricular ejection fraction and regional
      ejection fraction (rEF) were combined with the result of myocardial perfusion,
      sensitivity increased up to 89% of Gp A, 100% of Gp B. Diagnostic accuracy of
      LAD, LCX and RCA was 79%, 88% and 83%, respectively. Regional EF in ischemic
      areas decreased during EX in both Gps, particularly in Gp B. Regional EF in
      relatively normal perfusion areas did not significantly change in Gp A, but
      decreased in Gp B. These results suggest that 99mTc-tetrofosmin contributes to
      the improvement of sensitivity for CAD by combined assessment of EX-induced wall
      motion and myocardial perfusion abnormalities.

PMID- 8309106
TI  - [123I-OIH renoscintigraphy in children with chronic disorder of glomerulus].
AB  - To evaluate the usefulness of 123I-orthoiodohippurate (OIH) renography, 31
      patients with chronic disorder of glomerulus, from 5 years to 15 years old, were
      studied. In chronic glomerulonephritis and nephrotic syndrome with resistance to
      steroid therapy, Tmax and T 1/2 of the time-activity curve were statistically
      prolonged. Most of the renograms (time-activity curves) of the patients showed
      the hypofunction pattern. In most of the patients, other laboratory data,
      including BUN, PSP test and creatine clearance, didn't show abnormal values. 123I
      OIH scan was considered to be a sensitive and useful method to evaluate the renal
      function in pediatric patients with chronic glomerulonephritis.

PMID- 8309107
TI  - [Functional parameters calculated by 99mTc-MAG3 in transplanted kidney].
AB  - A newly developed 99mTc-labeled renal tubular agent, 99mTc
      mercaptoacetyltriglycine (99mTc-MAG3) was evaluated and compared with 99mTc-DTPA
      and 123I-OIH in 10 patients with a transplanted kidney. Renal uptake of MAG3
      correlated well with both DTPA and OIH; however, these uptake values of MAG3 were
      lower than those of OIH and higher than those of DTPA. Renogram parameters also
      correlated well with each other, but excretion of MAG3 was slower than that of
      OIH and faster than that of DTPA. The bladder to kidney ratio of MAG3 also
      correlated well, but these ratios of MAG3 were lower than those of OIH and higher
      than those of DTPA. In conclusion, MAG3 is a promising agent for evaluating the
      function of transplanted kidney.

PMID- 8309108
TI  - [Experimental study of per-rectal portal scintigraphy using 99mTc-HM-PAO].
AB  - Usefulness of per-rectal portal scintigraphy by 123I-IMP has already been
      admitted. We assessed whether 99mTc-HM-PAO, another agent used for cerebral blood
      flow scintigraphy, could be utilized for scintigraphic evaluation of the portal
      system. Animal experiments were carried out to evaluate the usefulness of the
      examination. Shunt indices obtained from per-rectal portal scintigraphy by 123I
      IMP and 99mTc-HM-PAO in shunt models and shunt rate obtained by direct injection
      of 99mTc-MAA into the inferior mesenteric vein under laparotomy were compared.
      Correlation coefficient of each agent with 99mTc-MAA was 0.90 for 99mTc-HM-PAO
      and 0.80 for 123I-IMP. It was also noted that as larger quantity of the tracer
      could be administrated in 99mTc-HM-PAO than in 123I-IMP, absorption from rectum
      was optimum and liver extraction fraction was 94.4%. Therefore, we concluded that
      99mTc-HM-PAO was useful for per-rectal portal scintigraphy.

PMID- 8309109
TI  - [Attenuation correction using postinjection transmission measurements for PET:
      the optimization of measurement conditions].
AB  - A new method of PET attenuation using post-injection transmission scan is
      presented, which is especially useful in 18F-FDG static studies. The transmission
      scan is acquired right before the emission scan, which is used to subtract the
      emission component from the transmission data. When the effect of measurement
      condition upon the image noise was evaluated with a 20 cm diameter cylindrical
      phantom, an increase in the injection dose inflated the noise and caused
      artifacts. There was an optimum dose that minimized the image noise. As the
      external source activity increased, the image noise decreased, and the optimum
      dose increased linearly, which enabled estimation of the optimum injection dose
      under a given external source. When the total (emission plus transmission) scan
      time was fixed, longer emission scan resulted in better images than longer
      transmission scan.

PMID- 8309110
TI  - [Assessment of left ventricular function with 99mTc-MIBI gated myocardial SPECT
      using 3 head rotating gamma camera].
AB  - Twenty-one patients with ischemic heart disease were studied by resting 99mTc
      methoxyisobutyl isonitrile (MIBI) gated SPECT images using a 3 head rotating
      gamma camera (Picker/Shimadzu: PRISM 3000). The data were acquired over 360
      degrees in 20 (x 3) steps, each of which was 70 beats. The systolic wall
      thickening index (%WT) was calculated as (ES count-ED count/ED count x 100),
      using the circumferential profile analysis of ED and ES short axial images. The
      %WT was correlated well with LVEF obtained from contrast ventriculography (r =
      0.85, n = 17). By using high speed (3 head) rotating gamma camera, we have
      shortened the time of collecting MIBI gated SPECT data, and this method can
      provide useful information on ventricular function.

PMID- 8309111
TI  - [Clinical usefulness of thallium-201 chloride in the diagnosis of tumors (I)-
      Evaluation in brain tumors].
AB  - Forty-eight patients with suspected brain tumor were studied to evaluate the
      clinical efficacy of Thallium-201 (201Tl) SPECT. 201Tl scintigrams showed
      abnormal accumulation in 24/26 (92.3%) and 9/14 (64.3%) of patients with
      malignant and benign tumors, respectively. 201Tl tended to be retained more
      prominently in malignant brain tumors than in benign ones. The lesion-to-normal
      ratios (L/N ratios) of 201Tl demonstrated significant correlation with those of
      18F-FDG (n = 5, r = 0.90, p = 0.044). L/N ratios were higher in patients with
      recurrent tumors than those with necrotic lesions (3.33 +/- 0.81 and 1.73 +/-
      0.81, respectively, p = 0.0123). The positive predictive value of L/N ratios > or
      = 2.5 for diagnosing as recurrence and L/N ratios < 2.5 as necrosis were 83.3%
      and 100%, respectively. These results suggest that 201Tl scintigraphy may be
      useful to determine the malignancy of brain tumors and to differentiate
      recurrence from necrosis after therapeutic procedures.

PMID- 8309112
TI  - [Clinical usefulness of thallium-201 chloride in the diagnosis of tumor (II)--An
      evaluation in bone, soft tissue and mediastinal tumors].
AB  - The clinical usefulness of scintigraphy with thallium-201 (201Tl) chloride
      injection was evaluated in 79 patients with suspected bone, soft tissue or
      mediastinal tumors. No abnormal changes of subjective or objective signs and
      clinical test values were observed post injection. It is considered that 201Tl
      chloride is a safe radiopharmaceutical. In comparison with benign tumors,
      malignant tumors showed longer retention or more increased uptake of the 201Tl in
      the lesions on delayed images. The results suggested that the evaluation of
      changes of 201Tl uptake might be useful to some extent to differentiate malignant
      tumor from benign tumor. It is considered that 201Tl scintigraphy is useful for
      evaluating the location and extent of tumor and differentiating malignant from
      benign tumor.

PMID- 8309113
TI  - [Clinical assessment of 99mTc-MAG3 scintigraphy for impaired renal function].
AB  - The renal scintigraphy and clearance of 99mTc-mercaptoacetyltriglycine (MAG3) and
      123I-ortho-iodohippuric acid (OIH) were compared in 12 patients with impaired
      renal function. The patients were first studied with MAG3 and then reinvestigated
      with OIH two days later. The MAG3 renal scintigraphy gave better quality and
      functional information in comparison with OIH. The MAG3 and OIH renogram showed
      identical relative kidney uptake and Tmax, but T1/2 of MAG3 was longer (p <
      0.001). The plasma clearance of MAG3 was lower than that of OIH, but they
      correlated significantly (r = 0.87, p < 0.005). Also, the plasma clearances of
      MAG3 and para-aminohippuric acid (calculated by the standard clearance technique)
      showed good correlation (r = 0.77, p < 0.05). The urinary excretion during the
      first 60 min after injection was the same for the two radiopharmaceuticals. We
      conclude that 99mTc-MAG3 is a suitable alternative to 123I-OIH in renal
      scintigraphy.

PMID- 8309114
TI  - [The role of Japan Radioisotope Association in nuclear medicine].
AB  - The Japan Radioisotope Association (JRIA) is established as a nonprofit
      organization operated by the users with the purpose of facilitating the
      utilization of RI. Its major activities include academic activities, supplying
      RI, labeled compounds and radiopharmaceuticals, and collecting and treating
      radioactive wastes. All RI, 90% of which is radiopharmaceuticals, are distributed
      through JRIA. The growing rate of radiopharmaceuticals is now getting slow, and
      RIA has a tendency to be replaced by nonradioactive assays. Nishina Memorial
      Cyclotron Center is to be operated for cooperative research projects of all
      institutions in Japan. Kaya Memorial Takizawa Laboratory is established to treat
      all medical radioactive wastes.

PMID- 8309115
TI  - [Histological study of the fetal kidneys. Development of the nephrons according
      to gestational weeks].
AB  - Despite recent advance of prenatal ultrasonography leading to an increase in the
      detection of various fetal urological abnormalities, a lot a unresolved problems
      exist surrounding their diagnosis and management. It is unclear whether an
      antenatal intervention helps to preserve the renal function, because little has
      been known about the nephrogenesis of the human fetal kidney associated with
      congenital obstruction. To find the normal development of the kidney, we studied
      the fetal kidneys in relation to the gestational weeks. Of all fetuses autopsied
      in the Department of Pathology of our Institute from 1982 to 1992, 87 kidneys
      from 60 fetuses which showed no abnormalities of the urinary tracts on
      macroscopic inspections were reviewed. Microscopic examination was done to define
      the radial glomerular count (RGC) and glomerular size according to gestational
      weeks. Nephrogenic zone was observed in all kidneys before 34 weeks of gestation,
      and disappeared in all kidneys after 37 weeks. The RGC increased steadily with
      gestational weeks, and gradually reached a plateau of around 12 counts at about
      36 weeks. The RGC was not influenced by the intrauterine fetal growth. The
      glomeruli were arranged in the uniform fashion on the medullary ray with the
      smallest in the most superficial cortex and the largest in the juxtamedullary
      zone. The superficial glomeruli remained at the surprisingly same size up to
      birth. Juxtamedullary glomeruli showed no significant differences before birth,
      either. Based on the present studies to know the normal standard of renal
      development, pathological changes are possible to define. It was thought that an
      understanding of the morphological characteristics of fetal kidneys would give
      clues to elucidate pathogenesis of abnormal kidneys.

PMID- 8309116
TI  - [Histological study of fetal hydronephrosis. Development background of prenatal
      treatment].
AB  - It is still unclear whether prenatal decompression of the dilated urinary tracts
      can preserve renal development and function. Following the previous report on the
      relationship between the nephrogenesis and the gestational weeks in normal
      fetuses, we studied the hydronephrotic kidneys to find the histological
      background of the fetal treatment. Of the fetuses autopsied in the Department of
      Pathology of our Institute from 1982 to 1992, 32 kidneys from 21 fetuses
      associated with dilatation of the upper urinary tracts irrespective of the
      presence of urethral obstruction on macroscopic inspections were reviewed. The
      underlying disorders causing hydronephrosis included urethral obstruction in 7,
      vesico-intestinal fissure in 3, hydrometrocolpos in 2 and double ureter in 1. The
      etiology of the hydronephrosis was not clarified in another 8. The position and
      configuration of the ureteral orifices were not described in the autopsy reports.
      Microscopic examination was done to define the radial glomerular count (RGC),
      presence or absence of the nephrogenic zone, cortical cysts and dysplastic
      elements, changes of the collecting tubules and interstitium. Of the kidneys 19
      had cortical cysts of various sizes. In some kidneys, the normal cortex was mixed
      with pathological segments where there were subcapsular small cysts and tubular
      dilatation. Nephrogenic zone, which was observed in specimens of 33-weeks fetus
      with moderate hydronephrosis, was already missing by 28 weeks in severe
      hydronephrosis. Collecting tubules were dilated in 12 kidneys with mild to
      moderate hydronephrosis. Tubular atrophy and increase in the interstitium were
      seen in 12 kidneys, eleven of which were of the fetus over 30 weeks.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8309117
TI  - [Immunohistological grade of renal cell carcinoma employing anti Leu-M1 antibody
      and anti EMA antibody].
AB  - Attempting to establish more objective grading system of renal cell carcinoma, I
      studied 104 renal cell carcinoma tissue samples from 52 cases by
      immunohistochemical technique employing the anti-Leu M1 antibody and the anti-EMA
      antibody. These 52 cases could be classified into 4 groups according to the
      reactivity for Leu-M1 (L) and EMA (E), i.e., L+E-, L+E+, L-E+, and L-E-.
      Considering the expression pattern of Leu-M1 (L) and EMA (E) in normal
      adult/fetal renal tissue, I speculated that normal cellular characters of the
      proximal tubules were preserved most well in the L+E- carcinomas, and gradually
      lost in the L+E+ carcinomas, L-E+ carcinomas, and L-E- carcinomas in this order.
      The reactions L+E-, L+E+, L-E+, and L-E- were designated immunohistochemical
      grade 1, 2, 3, and 4, respectively. In most cases, the immunohistochemical grade
      corresponded with the conventional histologic grade. However, dissociation of
      more than 2 steps of the grade was observed in some cases. I analyzed the cases
      with such dissociation and discussed usefulness of the immunohistochemical
      grading system (as a supplemental role for histologic grading) for renal cell
      carcinoma.

PMID- 8309118
TI  - [Transurethral teflon paste injection for vesicoureteral reflux in neurogenic
      bladder dysfunction].
AB  - We experienced transurethral teflon paste injection for 12 refluxing ureters of 7
      patients with neurogenic bladder dysfunction. Preoperative assessment of
      cystometry showed hypoactive bladder function with normal bladder compliance in 4
      patients, and low compliance bladder (< 10 ml/cmH2O) in 1. Voiding cystography
      revealed grade 1 reflux in 2 ureters, grade 2 in 3, grade 3 in 2, grade 4 in 2,
      and grade 5 in 2. One ureter did not show reflux. Zero point two to 1.6 ml of
      teflon paste was injected on each ureter under cystoscopic observation. These
      patients were followed for a mean of 25.1 months. Reflux disappeared immediately
      after the first operations in all patients, however recurrence was observed in 2
      ureters, in which improvement of reflux (grade 5 to 2) was achieved in 1 ureter
      but no improvement (grade 2 to 2) in another. Pyelonephritis was not encountered
      in any patients after injection. No complication was observed through the follow
      up period. In conclusion, we advocate that endoscopic teflon paste injection is a
      useful alternative to ureteroneocystostomy in the treatment of reflux in patients
      with neurogenic bladder dysfunction.

PMID- 8309119
TI  - [Staging pelvic lymphadenectomy for prostatic carcinoma].
AB  - Forty-two prostatic carcinoma patients with clinical stage A2, B or C underwent
      pelvic lymphadenectomy (limited node dissection) as a staging operation. The
      relationships among the presence of lymph node metastasis, tumor marker levels
      and histological findings of primary lesions were examined in 42 patients. Pelvic
      lymph node metastasis was noted in 18 (43%) of the 42 patients. The incidence of
      lymph node metastasis tended to be correlated with differentiation and Gleason's
      primary lesion sum. The preoperative PSA and PAP levels were significantly
      elevated in patients with positive lymph nodes for carcinoma than in those with
      negative lymph node for carcinoma. Patients with higher serum PSA (> or = 20
      ng/ml) and PAP (> or = 10 ng/ml) levels were more frequently associated with
      lymph node metastasis. Thus, when serum PSA and PAP were markedly elevated before
      treatment in patients with prostatic carcinoma, they should be considered to have
      a potential of pelvic lymph node metastasis. Pelvic lymph node metastasis was
      observed in some cases even without high tumor marker levels, particularly those
      with poorly differentiated carcinoma.

PMID- 8309120
TI  - [The effect of desmopressin (DDAVP) in patients complaining of nocturia].
AB  - The mechanism of increased nocturnal urine production in adult patients
      complaining of nocturia has seldom been reported. The objective of this clinical
      study is to investigate the circadian rhythm of both urine production and plasma
      arginine-vasopressin (AVP) level, and the efficacy of intranasal instillation of
      1-deamino-8-D-arginine-vasopressin (DDAVP) in adult patients complaining of
      nocturia. Eight patients (seven men, one woman) who ranged in age from 44 to 77
      years (mean 64.1 years) were examined. Three of them suffered from Shy-Drager
      syndrome, and no patient had shown any improvement of symptoms in spite of
      administration of anti-cholinergic agents and restriction of water intake.
      Nocturnal urine volume was more than bladder capacity in all patients, and no
      patient showed normal elevation of nocturnal plasma AVP level. Intranasal
      administration of DDAVP of 5 or 10 micrograms revealed marked decrease in
      nocturia, and nocturnal urine volume (p < 0.01). There were mild side effects
      (headache, nasal obstruction, and hyponatremia) not requiring any treatment. In
      conclusion, DDAVP is a safe and effective treatment for adult patients
      complaining of nocturia due to hyperproduction of nocturnal urine and
      inappropriate nocturnal secretion of AVP.

PMID- 8309121
TI  - [Ultrasonic diagnosis of renal cell carcinoma in hemodialysis patients].
AB  - Abdominal ultrasonic examination (US) was performed in 1556 patients on
      hemodialysis for 7 years and 6 months from April 1955 to September 1992. Renal
      cell carcinoma (RCC) proved histologically by operation was found in 36 patients
      (41 kidneys). Among the 36, RCC developed from the contracted kidney in 15, the
      individual kidney after renal transplantation in 3, and from ACDK (acquired
      cystic disease of the kidney) in 18. Among the 18 (ACDK), multiple tumors were
      found in the unilateral kidney in 8 and in bilateral kidney in 5. RCC was
      detected at the rate of 2.3% in patients on hemodialysis (1 out of 43). It was 29
      time as high as in healthy persons (RCC was found in 22 out of 27933 at our
      Health Check-up Center, 0.079%). RCC was diagnosed 100% by US, 68% by CT, and 55%
      by angiography. US is the most excellent examination for the diagnosis of RCC in
      patients on hemodialysis.

PMID- 8309122
TI  - [Progression and recurrence in the prostate and upper urinary tract following
      intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer].
AB  - A total of 13 patients received intravesical bacillus Calmette-Guerin (BCG)
      therapy for superficial bladder cancer and were followed for at least 6 months
      (range 6 to 50 months). Of the patients 7 had carcinoma in situ and 6 had
      recurrent tumors following intravesical mitomycin C therapy. Of the 7 patients
      who had carcinoma in situ, 4 (57%) are free of disease and 3 (43%) have required
      cystectomy for recurrence or progression. Of the 6 patients who had recurrent
      tumors following intravesical mitomycin C therapy, 3 (50%) remain free of tumor
      after BCG therapy alone, 2 (33%) had superficial recurrences but no progression
      and 1 (17%) has required cystectomy for prostatic involvement. After intravesical
      BCG therapy, transitional cell carcinoma of the prostate was identified in 4 of
      the 13 patients, and tumors in the upper urinary tract were detected in 2 of the
      4 patients with prostatic involvement. Of the 4 patients 2 have local recurrence
      or distant metastasis. In patients treated with BCG therapy the prostate and
      upper urinary tract represent a potential site of progression or recurrence.
      Patients treated with intravesical BCG therapy for superficial bladder cancer
      should be monitored closely for the development of transitional cell carcinoma of
      the prostate and upper urinary tract.

PMID- 8309123
TI  - [Effects of norepinephrine and alpha-1 adrenergic blockers on cultured stromal
      cell from benign prostatic hyperplasia].
AB  - Specimens obtained by open prostatectomy from patients with benign prostatic
      hyperplasia were used for primary stromal cell culture. Cell were treated with
      norepinephrine and alpha-1 blocker, prazosin. The cell proliferation was measured
      by 3H-thymidine incorporation and cell number. The cellular hypertrophy was
      assessed by flow cytometric analysis. Norepinephrine did not stimulate cell
      proliferation and prazosin did not induce to inhibit cell growth. Prazosin also
      did not have any effect on the hypertrophic stromal cell stimulated by serum. Our
      results suggested that alpha-1 adrenoceptors had no relation to the cellular
      hypertrophy or hyperplasia in the prostate.

PMID- 8309124
TI  - [A case of renal cell carcinoma treated by ex vivo partial nephrectomy and
      autotransplantation].
AB  - We report on a case of renal cell carcinoma in a functionally solitary kidney,
      treated by ex vivo partial nephrectomy and autotransplantation. A 62-year-old
      woman was admitted for examination of a left renal mass and right hydronephrosis,
      incidentally detected on echography and CT scan. The right hydronephrosis was
      caused by congenital ureteropelvic junction obstruction, associated with severely
      impaired renal function. A solid tumor was found in the left kidney, located in
      the upper pole and extending to the hilus, and was suspected to be renal cell
      carcinoma. The patient was treated by ex vivo partial nephrectomy of the left
      kidney followed by autotransplantation. The tumor was 35 x 55 x 40 mm in size and
      diagnosed histologically to be renal cell carcinoma. Hemodialysis was unnecessary
      since good urine output was obtained postoperatively from the transplanted
      kidney. The patient was discharged 3 months after surgery, following interferon
      alpha therapy, with serum creatinine level of 1.4 mg/dl.

PMID- 8309125
TI  - [Retroperitoneal liposarcoma with intrarenal metastases which was difficult to
      distinguish from angiomyolipoma. A case report].
AB  - A 40-year-old man was admitted to our hospital with a fat-density extrarenal
      tumor and intrarenal nodules which were detected by ultrasonography (US) and CT
      scan obtained the general health check. After his admission, US, CT, MRI and
      angiography were performed. As the final diagnostic procedure, we performed a US
      guided percutaneous needle biopsy of the extrarenal tumor, because this tumor was
      difficult to distinguish from liposarcoma and angiomyolipoma (AML). The
      pathological study revealed a well-differentiated liposarcoma, and the extrarenal
      tumor and the left kidney were removed en bloc. Pathologically, the tumor not
      only invaded into the renal parenchyma directly but also have metastasized
      independently to the intrarenal region. Postoperatively, he received a tumor dose
      of irradiation of 50 Gy. Liposarcoma arising in the perirenal space should be
      considered in the differential diagnosis of exophytic AML. If radiological
      studies can not confirm the appropriate diagnosis, we consider that biopsy of the
      tumor should be selected as an alternative diagnostic approach. And, we think
      that this is the first case report dealing with intrarenal metastases of
      liposarcoma.

PMID- 8309126
TI  - A New Year's resolution that saved my life.

PMID- 8309127
TI  - Emergency nursing in Poland.

PMID- 8309128
TI  - A look at our new emergency department. Triage renovation, University
      Hospital/University of New Mexico Medical Center, Albuquerque, New Mexico.

PMID- 8309129
TI  - President's message: scoping out our emergency nursing practice.

PMID- 8309130
TI  - 1993 Scientific Assembly research abstracts: introduction and reflections.

PMID- 8309131
TI  - Faster bed assignment for admitted patients: one emergency department's
      experience.

PMID- 8309132
TI  - "Quick fix" medication questioned.

PMID- 8309133
TI  - More on family presence during resuscitation.

PMID- 8309135
TI  - Additional suggestion for chest pain critical pathway.

PMID- 8309134
TI  - The presence of family during resuscitation attempts.

PMID- 8309136
TI  - Primary care demonstration project eases New Jersey ED patient load.

PMID- 8309137
TI  - Rectal versus axillary temperatures.

PMID- 8309138
TI  - Inhalation injuries: review and two case studies.

PMID- 8309139
TI  - Reported use of autotransfusion systems in initial resuscitation areas by one
      hundred thirty-six United States hospitals.
AB  - INTRODUCTION: The purpose of this study was to determine autotransfusion system
      availability and use in the initial resuscitation area. METHODS: A 22-item
      questionnaire was mailed to 290 facilities across the country; 136 (46.8%) were
      returned. Questions included availability and use of the autotransfusion system,
      patient population, resistance to the system, frequency of in-service programs,
      use of anticoagulants, and recommendations regarding the use of autotransfusion
      systems. RESULTS: One hundred seven hospitals (79%) reported autotransfusion
      system availability. Frequency of autotransfusion system initiation was as
      follows: always, 17 (15.9%); most of the time, 34 (31.8%); occasionally, 41
      (38.3%); and never, 15 (14%). Not all patients who had an autotransfusion system
      initiated received shed blood. The most frequent reasons for not using an
      autotransfusion system were as follows: "not requested by medical staff," n = 50;
      "no need for autotransfusion system," n = 33; "preferred banked blood," n = 25;
      and "did not use [often] enough to maintain skill," n = 21. Those with more than
      one in-service program per year were more likely to use an autotransfusion system
      than those with one in-service program per year. DISCUSSION: The majority of
      hospitals surveyed had autotransfusion system availability; however,
      autotransfusion system use was inconsistent. Two major areas influencing
      autotransfusion system use were having specific criteria for use and educational
      factors.

PMID- 8309140
TI  - Women, thrombolytic therapy, and the gender gap: recommendations for practice.

PMID- 8309141
TI  - How to report research with clarity, coherence, and grace.

PMID- 8309142
TI  - A suburban community emergency department's adaptation of case management.

PMID- 8309143
TI  - Munchausen syndrome: a test of clinical reasoning.

PMID- 8309144
TI  - Significant changes in Advanced Cardiac Life Support medication guidelines.

PMID- 8309145
TI  - What are some guidelines for restraint use in the emergency department?

PMID- 8309146
TI  - Emergency department nursing record.

PMID- 8309147
TI  - Trauma chart.

PMID- 8309148
TI  - Trauma admission checklist.

PMID- 8309149
TI  - "On call" staffing.
AB  - ED on-call programs can be a feasible staffing option, provided they are
      designed, implemented, and modified with responsive flexibility to meet both the
      institution's and staff's unique needs. Surveying similar health care facilities
      in a local area can guide the implementation and aid in perception of what type
      of on-call system would be most accepted in the area.

PMID- 8309150
TI  - Law and the emergency nurse. Professional malpractice or simple negligence?

PMID- 8309151
TI  - Oral rehydration therapy: a new document and standard of care.

PMID- 8309152
TI  - Designing a competency-based orientation for the emergency department.

PMID- 8309153
TI  - Cardiac contusion in a 2 1/2-year-old child.
AB  - This case was unique in that we were seeing signs and symptoms of a cardiac
      contusion 11 hours after injury, when cellular edema was causing lethal
      bradyarrhythmias and hypotension. Keeping the possibility of a cardiac contusion
      in mind when caring for pediatric patients with trauma and including a 12-lead
      EKG more routinely for pediatric patients with chest trauma would increase
      identification of potential problems as early as possible. Although cardiac
      contusion is not common in children, it must not be overlooked.

PMID- 8309154
TI  - "Trauma volunteers": vital members of the trauma team.

PMID- 8309155
TI  - Triage decisions: a 15-year-old boy with shortness of breath, hoarseness, and
      sore throat.

PMID- 8309156
TI  - Nursing leader Rita Celmer: the spirit of emergency nursing. Interview by Mary
      Bailey.

PMID- 8309157
TI  - The revelation.

PMID- 8309158
TI  - Up in smoke.

PMID- 8309159
TI  - Use of approved drugs for unlabeled indications.

PMID- 8309160
TI  - Smoking-attributable mortality in Kansas, 1990.

PMID- 8309161
TI  - The KUFP five-visit quit-smoking program.
AB  - This article has presented an overview of the Quit-Smoking Program developed and
      modified at the KUMC Department of Family Practice. Originally, this clinic was
      designed as a group treatment program, facilitated by a psychologist and
      physician. Recently, however, the program has been modified for office-based
      primary care physicians. Because smoking is such a deadly habit, it is hoped that
      physicians will take a more active role in smoking cessation efforts with their
      patients who are currently smokers.

PMID- 8309162
TI  - Frontal lobe dementia due to a meningioma.

PMID- 8309163
TI  - Surveillance for arboviral disease in Kansas, 1993.

PMID- 8309164
TI  - Midwestern PTCA utilization rates are highest.

PMID- 8309165
TI  - [Acute myocardial infarction with shock. Intracoronary thrombolysis].
AB  - Of 932 pts with acute myocardial infarction (AMI) who underwent reperfusion
      therapy (RT) by intracoronary streptokinase (IC.STK), 32 pts had cardiogenic
      shock (CS). Shock was defined as systolic blood pressure (BP) < or = 80 mmHg
      without inotropic support or BP < or = 90 mmHg with inotropic or balloon
      counterpulsation support and left ventricular end diastolic pressure < 18 mmHg
      and clinical symptoms of hypoperfusion. Time from onset of symptoms to initiation
      of therapy was less than 6 hours. Reperfusion was defined as reestablishment of
      antegrade TIMI-2 or 3 flow in occluded artery. Comparison revealed no significant
      differences in sex, age, time after onset of symptoms, artery involved, history
      of previous AMI, left ventricular ejection fraction and in extent of coronary
      disease between pts with successful and failed thrombolysis. IC.STK was
      successful in 12 pts with CS (37.5%) and in 67.2% of pts without CS (p < or =
      0.001). Mortality rate in pts with CS was 25% in reperfused and 81.8% among
      nonreperfused (p = 0.0095). CONCLUSIONS: 1. IC.STK gives a considerably lower
      rate of reperfusion in pts with AMI complicated by CS. 2. No influence on the
      frequency of effective reperfusion with respect to the analyzed clinical and
      angiographical data was found. 3. The high mortality in the group with
      unsuccessful reperfusion as well as the low effectiveness of the IC STK indicates
      the necessity to apply more effective methods of reperfusion in pts with AMI
      complicated by CS.

PMID- 8309166
TI  - [Cardiogenic shock. Coronary angioplasty after failed intravenous thrombolysis].
AB  - Rescue coronary angioplasty (PTCA) was employed as reperfusion strategy after
      unsuccessful intracoronary infusion of streptokinase in 13 patients with AMI
      complicated by cardiogenic shock (CS). Reperfusion defined as reestablishment of
      TIMI 3 degree flow in the infarct related artery and reduction in luminal
      narrowing to less than 50% was achieved in 8 patients (61.5%). The failure of
      PTCA was caused by: inability to cross occlusion in 2 patients and recurrent
      thrombosis despite repeated dilatations resulting in hemodynamic instability
      requiring cardiopulmonary resuscitations during the procedure in 3 patients.
      There was no significant differences in mean age, sex, time from onset of
      symptoms, LVEF, artery involved, extent of coronary disease and incidence of
      cardiopulmonary resuscitations during the procedures. There where 4 in-hospital
      deaths among patients with failed PTCA (80%) compared to 25% mortality in
      reperfused group. We conclude that PTCA is an effective method of achieving
      reperfusion in patients with CS complicating AMI after failed thrombolysis with
      intracoronary streptokinase and that it improves in-hospital survival.

PMID- 8309167
TI  - [Morphology of atheromatous change during and after PTCA and occurrence of
      restenosis].
AB  - The frequency of restenosis incidence in a group of 72 patients after effective
      PTCA as well as dependence of its incidence on dilated coronary artery and
      morphology of sclerotic changes according to ACC/AHA classification were
      analyzed. The subject of analysis included also effect of the degree of residual
      stenosis on restenosis incidence as well as determining dependence between the
      degree of dissection after PTCA on restenosis rate. Restenosis was stated in 20
      (20.7% percent) patients, in 26 cases (29%) among 88 dilated coronary arteries.
      Restenosis was more frequently observed in cases of left coronary artery
      dilatation. Analyzing restenosis occurrence in relation to morphology of
      sclerotic changes according to ACC/AHA classification its more frequent incidence
      in type B (35%) and type C (44%) in comparison type A--25% of this classification
      was observed. The percentage of residual stenosis was higher in the group of
      restenosis and amounted to 22.8% in comparison to the residual stenosis of 13% in
      the group of patients with no reported restenosis. Localized dissection can be a
      good predictor of results after successful PTCA. More frequent incidence of
      limited dissection took place in 34% of dilated coronary arteries without
      restenosis in relation to 20% of cases with restenosis. No evidence of dissection
      as well as long dissection after PTCA was associated with higher degree of
      restenosis. Angiographic evaluation of the morphology of sclerotic changes in
      view of degree of dissection after PTCA is a good predictor of results after
      angioplasty.

PMID- 8309168
TI  - [Heart rhythm variation and electrophysiologic parameters of the sino-atrial
      node].
AB  - Sinoatrial node (SAN) function depends on its intrinsic properties and on
      regulatory influences of autonomic nervous system. Disturbances in these both
      factors are responsible for intrinsic and extrinsic SAN dysfunction (SAND),
      respectively. Heart rate variability (HRV) is a reliable noninvasive marker of
      cardiovascular autonomic control. We examined 120 patients (pts) with syncope,
      palpitations and/or bradycardia (< 40 bpm during daily activity). In these
      patients, after one-minute oesophageal-ECG recording for HRV assessment, rapid
      continuous and programmed premature transesophageal left atrial pacing (TAP) were
      performed. Regarding the results of TAP, pts were divided into two groups: group
      I included 57 subjects with negative TAP, and group II consisted of 63 pts with
      positive TAP (SAND). We analysed two HRV parameters: variation ratio (VR, %) and
      maximal difference of any two consecutive sinus cycle lengths (DSCL, ms). The
      following TAP variables were calculated: corrected sinus node recovery time
      (CSNRT), second pause time (SPT) and calculated sinoatrial conduction time after
      Strauss (SACT). RESULTS: Mean DSCL was significantly shorter in group I (106 +/-
      96) than in gr. II (151 +/- 169) (p < 0.05). Similarly behaved VR values. In SAND
      pts with abnormal CSNRT or SPT we observed significantly greater VR and DSCL.
      This correlation was not confirmed in respect to SACT. We corroborated the
      significant coincidence of high HRV (VR < 20.0 and DSCL > 100) with pathologic
      CSNRT or SPT, but not with SACT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309169
TI  - [Coronary ultrasonography. More exact than coronary angiography? Description of
      two case histories].
AB  - Coronary angiography as the "golden standard" in diagnostic imaging, guiding and
      assessing the results of interventional therapy has well known limitations
      inherent to the two dimensional imaging of three dimensional structures.
      Intravascular ultrasonography provides cross-sectional images of coronary artery,
      allowing an accurate calculation of cross-sectional luminal area and assessment
      of the degree of eccentricity of plaque and its structure including fissures,
      dissections and intracoronary thrombi. Case 1: Coronary angiography was performed
      in a 60 y. male patient with unstable angina revealing only a 40% stenosis in
      proximal LAD. The inconsistency of clinical presentation with angiography
      findings led to perform an intravascular ultrasound (IVUS) examination of LAD.
      The angiographic 40% stenosis was found to be over 80% on IVUS. Subsequent PTCA
      procedure led to a good IVUS and clinical result with no obvious changes in
      angiography. Case 2: PTCA of 80% Cx stenosis was performed with good immediate
      angiographic result, without dissection nor residual stenosis. However, IVUS
      immediately after PTCA assessed a dissection of the plaque with a flap protruding
      into the lumen. The patient was sent back to coronary angiography several hours
      later with clinical and ecg symptoms of acute myocardial ischemia. An important,
      occlusive dissection was found at the PTCA site. Angioplasty was performed again
      restoring a wide lumen at intervention site. IVUS was able to clarify the
      ambiguous angiographic findings with an important impact on interventional
      therapy. The immediate results of invasive procedures were readily and safely
      assessed by intravascular ultrasound.

PMID- 8309170
TI  - [Doppler microprobe allows evaluation of local coronary circulation].
AB  - The local coronary flow in 42 patients (mean age: 59 +/- 9 years) with ischemic
      heart disease was assessed by means of an 0.018" intracoronary Doppler guidewire.
      Study population was divided into two groups: group I--"normal vessels" (diameter
      stenosis < 30%) and group II--"stenosis vessels" (diameter stenosis > 60%).
      Measurements of: averaged peak velocity (APV), diastolic-systolic velocity ratio
      (DSVR) were performed in proximal segments of normal vessels and proximally to
      stenosis in group II. APV and DSVR were recorded at rest (bas) and during
      papaverine induced hyperemia. Coronary flow reserve (CFR) was calculated as ratio
      hyperemic and resting values of APV. Mean value of APV at rest was highest for
      left main stem, lowest for venous by-passes (SVBG) but did not differ among three
      coronary arteries (LAD, LCX, RCA). CFR value was significantly higher for group I
      then for group II (2.75-3.3 vs 1.8-2.0) but did not differ significantly among
      particular arteries in both groups. Mean value of DSVRbas in both examined groups
      was lowest for right coronary artery and for SVBG (ca. 1.0) and did not change
      significantly during hyperemia. This value was significantly higher (ca. 2.0) for
      left coronary arteries (LAD, LCX) then for RCA and SVBG and significantly
      decreased after administration of papaverine.

PMID- 8309171
TI  - [Doppler microprobe for evaluation of coronary circulation after successful
      coronary angioplasty].
AB  - The influence of angiographically successful coronary angioplasty (PTCA) in 27
      patients (mean age 64 +/- 8 years) was assessed by means of 0.018" intracoronary
      Doppler guidewire. Averaged peak flow velocity (APV) and diastolic-systolic
      velocity ratio (DSVR) were recorded in resting conditions (bas) and during
      papaverine induced hyperemia before and after PTCA. Coronary flow reserve (CFR)
      was calculated as ratio of hyperemic and resting APV. The parameters mentioned
      above were estimated proximally and distally to coronary stenosis to be dilated.
      Mean value of APVbas for distal part of the vessels was significantly lower
      (about 46-57%) then for the two proximal segments. PTCA caused significant
      increase of APVbas as for proximal (about 21-69%) as for distal segments (about
      62-77%). That procedure caused significant increase of CFR only for right
      coronary artery (RCA). Mean values of DSVRbas in proximal position for left
      descendens (LAD) and left circumflex (LCx) arteries before PTCA were
      significantly higher than DSVbas for distal position but did not differ for RCA.
      PTCA caused significant increase of DSVRbas in distal position only for LAD and
      LCx. Our results showed that angiographically successful PTCA causes significant
      increase of APVbas for right and left coronary arteries and normalization of
      DSVRbas in distal segments of LAD and LCx.

PMID- 8309172
TI  - [Peculiarity of myocardial heart diseases in women].

PMID- 8309173
TI  - [The pharmacodynamics of the new anti-arrhythmia preparation bonnecor based on
      the data from an acute drug test].
AB  - The pharmacodynamics of the new antiarrhythmic agent bonnecor was studied in 33
      patients with coronary heart diseases and ventricular arrhythmias in the acute
      drug test. The parenteral formulation of the drug (0.04-0.8 mg/kg) and its
      tablets were given to 23 and 27 patients, respectively. Bonnecor was found to be
      effective in suppressing ventricular premature contractions. Its intravenous and
      oral efficacy is 65 and 70%), respectively. During intravenous injection, the
      drug showed its antiarrhythmic effect on an average of 14 minutes later, lasting
      about 68 minutes. During oral administration, the action of the drug started 0.5
      hour later and lasted 7.2 hours. Adverse reactions were rare. An
      echocardiographic study revealed its negative inotropic effect which is likely to
      be insignificant since there was no development or increase of heart failure in
      any of the examinees (including 8 patients with signs of Stage I-IIA circulatory
      insufficiency).

PMID- 8309174
TI  - [Neoton in the treatment of myocardial infarct and unstable stenocardia].
AB  - A total of 485 patients with complicated myocardial infarction (MI) in the
      presence of concurrent abnormality and 104 patients with unstable angina (UA)
      were followed up. Intravenous infusion of neoton (phosphocreatine) in a dose of
      70 g at day 1 and 36 g at days 2 and 3 of the onset was made in 96 patients with
      MI, 28 patients with UA took neoton in a daily dose of 30 g during 3 days.
      Control patients had conventional therapy, In UA, poor outcomes (death, MI, no
      effects, referral of patients for bypass surgery) were seen in 4 (14%) patients
      on the drug and in 18 (28%) in the controls (p > 0.05). In MI, more rapid
      disappearance of events (heart failure and tachyarrhythmias) was observed in the
      major group, the mortality being 23.9%, the incidence of cardiac ruptures 6.4
      versus 33.6 and 12.6% respectively, in the control. It is concluded that large
      dose neoton exerts positive action on the cause and outcome of UA and complicated
      MI.

PMID- 8309175
TI  - [Cardiodynamics and myocardial contractile reserve in patients with hypertrophic
      cardiomyopathy].
AB  - Cardiodynamics and myocardial contractile reserve were studied in 60 patients
      with hypertrophic cardiomyopathy by using radionuclide ventriculography at rest
      and during graded exercise test. All findings that characterize cardiodynamics
      (normal or higher overall ejection fraction and stroke volume or lower end
      systolic volume, higher maximum ejection rate) show the contractility of the left
      ventricle in patients with hypertrophic cardiomyopathy which can be regarded to
      be more severe. During graded exercise test, in patients with hypertrophic
      cardiomyopathy three types of reactions were identified: (1) positive inotropic
      effect; (2) negative inotropic effect; (3) intermediate (deviation of major
      cardiodynamic parameters was no more than 20-25% of the baseline levels).
      Identification of the above types allows one to assess the presence and
      conditions of myocardial contractile reserve implementation in these patients and
      to objectivize the choice of corrective drugs.

PMID- 8309176
TI  - [An evaluation of the course and prognosis of hypertrophic cardiomyopathy in
      relation to the presence of circulatory failure].
AB  - A total of 55 patients with hypertropic cardiomyopathy (HCMP) with and without
      circulatory insufficiency were examined at rest and in the restorative period (up
      to 24 hours) after graded exercise. The serum levels of lactate were measured and
      the activity of lysosomal enzymes: acid phosphatase, beta-glucosidase and beta
      galactosidase were assayed. Healthy untrained donors (n = 21) and athletes (n =
      12) with moderately working myocardial hypertrophy, as evidenced by
      echocardiography served as controls. The patients with HCMP had higher lactate
      levels and enhanced activity of lysosomal enzymes both at rest and during
      exercise than the controls. Highest hyperenzymia was found in HCMP patients with
      circulatory insufficiency and in those without the latter who showed progressive
      disease even with signs of circulatory insufficiency during 6-9 month follow-ups.
      In these groups, the patients had the lowest capacity to restore after exercise.
      It is concluded that the high activity of blood lysosomal enzymes in HCMP
      patients is a poor predictor.

PMID- 8309177
TI  - [Cardiomyopathies in the practice of sports medicine].
AB  - In the past 10 years, cardiomyopathy has been diagnosed in 16 athletes, out of
      them in 13 this abnormality has been ascertained for the first time when they
      were examined or they were in the outpatient department. The paper provides
      clinical and instrumental findings of 13 patients with hypertrophic cardiopathy
      and 3 with dilated cardiomyopathy whose diagnosis was established by making a
      differential diagnosis of congenital and acquired heart diseases, coronary heart
      disease, essential hypertension and athletic heart. Most athletes with
      hypertrophic cardiomyopathy has an asymptomatic or mild natural history.

PMID- 8309178
TI  - [Atherosclerotic heart defects].
AB  - Clinical, echocardiographic, Doppler echocardiographic, electro- and
      phonocardiographic studies were performed in 31 patients with cardiac
      atherosclerotic lesions (aortic in 17 patients, aortomitral in 10, mitral in 4)
      and in 20 patients matched for age, sex, and underlying abnormality, but without
      cardiac disease. Atherosclerotic defects caused by calcification of the valvular
      apparatus were shown to be rarely (5.9% of patients) isolated, they were more
      frequently combined or concurrent. Atherosclerotic defects caused no significant
      myocardial structural and functional changes in addition to the underlying
      pathology. Aortic atherosclerotic stenosis is diagnosed at equal rates by using
      echo and phonocardiography, whereas aortic valvular insufficiency and mitral
      diseases are better (7- and 9-fold) detected with echocardiography and Doppler
      echocardiography, whereas aortic valvular insufficiency and mitral diseases are
      better (7- and 9-fold) detected with echocardiography and Doppler
      echocardiography than with phonocardiography.

PMID- 8309179
TI  - [Retrograde blood circulation and ischemic heart disease].
AB  - The author performed experiments on 350 dogs and X-ray postmortem studies of 1520
      corpses of subjects who had died of various diseases and injuries. It was found
      that in occlusive great vessels in the ischemic organs and tissues, retrograde
      circulation developed, which completely maintained their viability under definite
      conditions. Retrograde venous blood flow to diseased organs and tissues
      drastically increased in insufficient retrograde arterial blood circulation.
      Under certain conditions, surplus venous blood influx caused edema and their
      dysfunctions. The mechanisms of retrograde circulation account for asymptomatic
      occlusion of the great vessels.

PMID- 8309180
TI  - [The bicycle ergometry test in the functional assessment of the cardiovascular
      system and kidneys].

PMID- 8309181
TI  - [The classification of ischemic heart disease].

PMID- 8309182
TI  - [The classification of ischemic heart disease (a comment on the article by A. S.
      Melent'ev and V. A. Kruglov in Kardiologiia, 1991, vol. 31, no. 7, pp. 77-80)].

PMID- 8309183
TI  - [The classification of IHD].

PMID- 8309184
TI  - [The classification and formulation of a diagnosis of ischemic heart disease].

PMID- 8309186
TI  - [A trial of the clinical use of the Russian hypocholesterolemic preparation
      fenbutol--an analog of probucol].
AB  - Phenbutol, a Russian analogue of probucol, was studied by the single blind method
      by using placebo in 30 patients aged 36 to 65 years whose total serum cholesterol
      levels were more than 250 mg/dl after a month placebo therapy. The patients were
      divided into two groups: (1) 15 patients on placebo and (2) 15 patients on
      phenbutol, 500 mg twice a day for 5 months. Blood lipid parameters were monthly
      determined. The findings are in agreement with the data on the effects of
      probucol on lipids and its adverse effects. During the follow-up, phenbutol
      showed 17%, 14% and 10% decreases in total cholesterol and low density
      lipoprotein cholesterol and high density lipoprotein cholesterol, respectively,
      as compared with the baselines. These changes were greater than those in patients
      on placebo. In the first week of therapy with phenbutol, vomiting, appetite
      decrease, digestive disturbances were observed in 73% of patients. These adverse
      reactions did not require its withdrawal. Resting ECG Q-T interval became
      prolonged in 7 out of 15 patients receiving phenbutol (maximum 500 msec).

PMID- 8309187
TI  - [Difficulties and errors in the diagnosis of aortic cardiac defects].

PMID- 8309188
TI  - [The mechanisms of the development of the papillary muscle dysfunction syndrome].

PMID- 8309189
TI  - [Obliteration of vessels growing into the cornea with the help of laser energy].
AB  - The vessels proliferating into cornea cause epithelium biotransformation and
      lipid keratopathy, decreasing corneal transparency. In 9 patients (10 eyes) argon
      laser obliteration of these vessels was performed. In 8 eyes improvement of
      corneal transparency and visual acuity was achieved, in other two the
      neovascularization was restrained. The best results were observed in lipid
      keratopathy.

PMID- 8309190
TI  - [Genetic basis of Leber's hereditary optic neuroretinopathy].
AB  - Basic information about mitochondrial inheritance have been presented. The nature
      of inheritance of Leber's hereditary optic neuroretinopathy (LHON) has been
      described. The recent reports about heterogeneity of mutations, heteroplasm and
      nucleo-mitochondrial interaction have been taken into consideration. Principles
      of modern genetic diagnostics and counselling of LHON have been described.

PMID- 8309191
TI  - [Evaluation of visual evoked potentials and static perimetry in chiasmal tumors
      and retrobulbar neuritis].
AB  - The author presented results of visual evoked potentials and static perimetry
      examinations performed in 17 patients with chiasmal tumors and in 27 with
      retrobulbar neuritis. A comparative analysis of the gathered parameters was done,
      using computer programs. The results suggest that the applied non-invasive
      methods of examination could be useful in differential diagnosis of these
      diseases.

PMID- 8309192
TI  - [Value of ERG examination in evaluation of retinal function in children and youth
      with type I diabetes].
AB  - The methods of studying early phases of diabetic retinopathy were presented. ERG
      as a method of examination of the functional activities of the retina was
      described. A variety of hypotheses concerning origination of oscillatory
      potentials (OPs) as well as their status in the early stage of diabetic
      retinopathy were outlined.

PMID- 8309193
TI  - [Effect of diabetes type I duration on changes of oscillatory potentials in ERG
      of children and youth].
AB  - Oscillatory potentials (OPs) of ERG in 70 juvenile patients (140 eyes) with
      visual acuity 1.0, suffering from insulin-dependent diabetes were analyzed.
      According to the duration of the disease, the patients were divided into 4
      groups. A significant diminution of the OPs amplitude in the group of patients
      with diabetes lasting more than 10 years was observed. An extension of implicit
      times of OPs were discovered starting with the group of patients with diabetes
      lasting over 5 years.

PMID- 8309194
TI  - [Evaluation of surgical methods of treatment for retinal detachment].
AB  - During last year we have used episcleral buckling and cryopexy in 63 eyes with
      retinal detachment. Final reattachment of the retina after 6 months follow-up was
      achieved in 52 eyes (83%) after one or two surgical procedures. 4 patients
      refused further surgery. In 7 cases pars plana vitrectomy and silicone oil
      tamponade were used. In 4 cases complete retinal reattachment was obtained. In
      further 2 eyes central retina was attached but flat detachment in the lower part
      of the retina was observed. Visual acuity of 0-0.5/50 was achieved in 5 eyes,
      1/50-4/50 in 5 eyes, 5/50-5/12 in 18 eyes and 5/10-5/5 in 35 eyes. Our results
      show that the majority of cases with retinal detachment can be successfully
      treated with episcleral buckling and cryopexy. Pars plana vitrectomy and silicone
      oil tamponade allowed some success in only the small number of eyes that
      otherwise would have a prognosis.

PMID- 8309195
TI  - [Treatment of retinal detachment with macular hole].
AB  - The authors presented 6 cases of macular hole retinal detachment in which pars
      plana vitrectomy with endo-tamponade was performed; in 4 cases SF6 gas and in 2,
      with PVR silicone oil was used. Retina was completely attached in 4 eyes. Visual
      acuity 1/50 to 2/50 was achieved in 5 eyes. Follow-up ranged from 5 to 9 months.

PMID- 8309196
TI  - [Traumatic rupture of the optic nerve in a 14-year old boy. Case report].
AB  - A case of 14-year boy with the optic nerve avulsion from the eyeball is
      presented. There were no changes in the anterior segment of the eye and
      pathological findings in the x-ray examination. Diagnostic difficulties and the
      probable pathomechanism of the injury are discussed.

PMID- 8309197
TI  - [Traumatic avulsion of the optic nerve in the chiasm region].
AB  - Avulsion of the optic nerve in the chiasmal region is a very rare injury. The
      authors presented a case of such avulsion with concomitant temporal visual field
      defect in the other eye. The pathomechanism of this type of optic nerve injuries
      is discussed.

PMID- 8309198
TI  - [Ultrasound screening of newborn infants. Uses and role in routine diagnosis].
AB  - The results of sonographic brain, renal and hip studies in 3396 clinically
      healthy, consecutive newborns during two and a half years are correlated to
      various anamnestic, clinical and ultrasound data. In the nearly sex-matched
      babies there were 4.2% anomalous brain studies, 4.4% renal studies followed by
      further diagnostic and therapeutic steps, and 7.4% right-sided and 9.7 left-sided
      hip dysplasias. A statistically significant dependence of neurosonographic
      findings from the delivery mode and a significant amount of renal abnormalities
      in turkish babies and infants of other nationalities were remarkable. The
      ultrasound hip studies confirmed the significantly higher rate of left-sided hip
      dysplasias in baby girls found in other studies. 80% of the initially diagnosed
      hip dysplasias type IIa according to Graf matured within the first six weeks of
      life. After six weeks there remained 4.2% hip dysplasias type IIg to type IV
      (luxation) which were treated. Breech-delivered infants, especially if manually
      handled, had delayed hip maturation. In turkish babies we found relatively more
      normal hip exams. Hip symptoms clinically proved correlated significantly with
      pathologic ultrasound hip studies. Statistically proved correlations between
      initially measured and follow-up alpha- angles provide the possibility to
      prognose the hip maturation using a regression-equation. Whereas the value of an
      ultrasound brain-screening is still in discussion, the authors believe that the
      introduction of a general ultrasound-screening of the urinary system and hips is
      mandatory.

PMID- 8309199
TI  - [Legal limits in the treatment of severely handicapped newborn infants?].
AB  - For the determination of legal limits in the care of seriously impaired newborns
      no real or presumed decisions of the patient are at hand. An autonomy of the
      patient (such as informed consent/refusal) does not exist nor do individual signs
      that would allow assumptions about the newborn's will. Also, decisions of the
      legal guardians are not binding if they are directed against the child's
      interests. Judgements based on arguments that consider social and psychological
      facts must be rejected as well as considerations about the rightfulness of an
      abortion on eugenic grounds. Solely general legal principles and norms can serve
      as a guideline for the determination of such limits: "life" as the most precious
      value guaranteed by constitution, the ban of the killing of any human being as a
      criminal act, the physicians general objectives that are based on professional
      ethics and affect law. From this can be deducted: Any obligation of the physician
      ends with the cerebral death of the patient. The obligation to prolong life
      ceases with: irreversible coma, or if necessary operations would result in such
      coma, or if life that befits a human being can never be secured without the help
      of mechanical ventilation, or if survival would constantly require new serious
      operations, or if imminent death could only be postponed for a short period of
      time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309200
TI  - [Increased incidence of developmental hip dysplasia in hypertrophic newborn
      infants].
AB  - "Lack of space" in utero is considered to be a major factor in the aetiology of
      the congenital dislocation of the hip. This study tries to answer the question
      whether hypertrophy of a newborn has to be regarded as a risk factor on the basis
      of the principle mentioned above. The results of postnatal clinical and
      sonographical examination performed on 98 large-for-gestational-age (LGA-)
      newborn were compared to those performed on 310 newborn children during a non
      selective screening program. Among the LGA-newborn pathological hip joints were
      found more often mainly female LGA-newborn infants were affected. It seemed that
      the birth weight did not correlate to the extent of the retardation of the hip
      joint development. It was again confirmed that the restriction to only clinical
      diagnostic procedures in the neonatal period is not effective in the early
      diagnosis of the malformation. Hypertrophy of a newborn has to be considered as a
      risk factor behind the development of congenital dislocation of the hip. It is
      recommended to examine all LGA-newborn infants post partum by clinical and most
      importantly also by sonographical means to recognize a retardation of hip joint
      development.

PMID- 8309201
TI  - [Near-infrared spectroscopy--a new method for non-invasive monitoring of cerebral
      hemodynamics].
AB  - Non-invasive techniques allow monitoring in prematures and newborns with the
      maxime of "minimal handling". Cerebral changes in oxi- and deoxihemoglobin and in
      total hemoglobin, which reflects the intracranial blood volume, can be monitored
      continuously by near infrared spectroscopy (NIRS) for the first time. As derived
      parameter the cerebral blood flow can be determined. With reservations the method
      allows to get a view of the cellular level by recorded changes of the
      cytochromeoxidase. This article gives a survey of the physics, the technique and
      shows the clinical application of the method.

PMID- 8309202
TI  - [Can follow-up scintigraphy be a decision aid for therapy choice in Perthes
      disease?].
AB  - In the period from 1988 to 1982 91 patients with M. Legg-Calve-Perthes received
      orthopaedic treatment. In 51 cases surgical treatment for femoral head
      containment by intertrochanteric derotation varus osteotomy was performed. 40
      patients were treated conservatively. Most cases received a Thomas-splint to
      eliminate weightbearing on the affected hip, some used crutches. Out of this
      group we present 6 cases that showed during the time of their first examination
      the radiologic stages 1 and 2 according to Waldenstrom. At the time when the M.
      Perthes was diagnosed these patients received a radionuclide bone scan, which was
      repeated of the average 6 months later to aid in the choice of therapy. Two other
      cases are presented for comparison, who received the first bone scan in the
      Perthes stage 2 and 3 according to Waldenstrom (fragmentation stage) showing an
      activity defect and were then operated with a derotation varus osteotomy after
      the follow-up bone scan had not shown revascularisation. All patients that had a
      complete revascularisation in the follow-up bone scan during the fragmentation
      stage had a good final result after conservative treatment. For other cases,
      where the bone scan in the fragmentation stage shows a persisting lack of
      epiphysis perfusion, it is recommended to decide for surgical treatment with
      derotational varus osteotomy, since the development of "head-at-risk" signs is
      likely, which will not resolve after later surgery.

PMID- 8309203
TI  - [Pediatric characteristics of adult respiratory distress syndrome: a meta
      analysis].
AB  - A meta-analysis of the literature is carried out in order to present the current
      knowledge of ARDS in childhood (0-15 years). This might be helpful for planning
      controlled studies on new therapeutic measures (e.g. surfactant replacement,
      antioxidants, extracorporeal gas exchange). By means of Medline all available
      publications were taken into account referring to minimal criteria defined
      before. There were 4 studies (50 patients) and 48 individual case-reports (48
      patients). Most often ARDS was caused by infection (21 resp. 30%), aspiration (12
      resp. 23%) and trauma (10 resp. 23%). Therapeutically high respiration pressures
      and toxic oxygen tensions were applied generally (average maximum PEEP: 14.7
      resp. 15.8 cm H2O; average maximum PIP: 59.6 resp. 61.9 cm H2O; FiO2 > 0.5 for an
      average of 10.1 resp. 10.4 days). The most frequent complications were barotrauma
      (43.8 resp. 78%), infection (60.4%) and multiorgan failure (66.7%). Mortality
      rate was 31.3 resp. 52%. So also in childhood almost every second case is fatal.
      Especially multiorgan failure as well as high levels of FiO2 and PEEP indicate
      bad prognosis at an early stage. Therefore it is necessary and justified to
      perform clinical trials on therapeutic agents successfully tested in animal
      studies before.

PMID- 8309204
TI  - [Vitamin D status of children and adolescents of African and Asian diplomats in
      Germany].
AB  - Vitamin D-deficiency has been observed among immigrant children with rickets and
      osteomalacia in Western Europe. So vitamin D-status in 34 children and juveniles
      (17 girls, 17 boys) of African and Asian diplomats staying in West Germany only
      for a certain time is examined. During summer 1989 plasma levels of alkaline
      phosphatase, calcium, phosphate, 25-hydroxy-cholecalciferol and 1,25
      dihydroxycholecalciferol is measured. According to their native country the
      subjects are divided into three groups: I North Africa (n = 7), II Central Africa
      (n = 18), III Asia (n = 9). No clinical signs of rickets or osteomalacia are
      detected. All plasma levels of calcium and phosphate are in the normal range so
      as most of the values of the alkaline phosphatase. In Group I 85.7% (n = 6),
      group II 77.8% (n = 14) and group III 44.4% (n = 4) have decreased values of 25
      OHD whereas most strikingly elevated amounts of 1,25-OH2D are measured in 57.1%
      (n = 4) of the subjects in group I, 66.7% (n = 12) in group II and 11.1% (n = 1)
      in group III. Normal values for both 25-OHD and 1,25-OH2D are rare: one case
      (11.1%) in group I, no case in group II, four cases (44.4%) in group III. The
      influence of the time staying in West Germany on vitamin D-status, a possible
      dietary lack due to inadequate nutrition, the role of skin pigmentation and a
      potential genetic abnormality of vitamin D-metabolism is discussed to explain the
      results.

PMID- 8309205
TI  - [Ceftriaxone-induced cholelithiasis--a harmless side-effect?].
AB  - 43 children suffering from borreliosis, meningitis and septicemia were treated
      with ceftriaxone. A six year old boy with acute jaundice due to ceftriaxone
      induced cholelithiasis encouraged us to reevaluate the frequency of ceftriaxone
      induced cholelithiasis and its' sequelae in children in a prospective study. Out
      of 43 children (age 6.3 years, 4 months to 16 years, male: female 25:18), 20
      children (46.5%) showed sonographical evidence for ceftriaxone induced
      cholelithiasis after a treatment of at least 10 days. Two of them even had signs
      of intrahepatic cholestasis, 3 kids suffered from severe abdominal pain, non of
      them showed serologic abnormalities. Another 5 children (11.6%) had sludge in the
      gallbladder without evidence for cholelithiasis. In all patients the
      "pseudocholelithiasis" spontaneously resolved within at most 2 months. We suggest
      a sonographical examination of the gallbladder at the end of the ceftriaxone
      treatment in order to detect cholelithiasis, which might call for further
      monitoring and maybe dietary treatment.

PMID- 8309206
TI  - [Nutritional iodine status of healthy infants in Germany].
AB  - In 78 healthy term babies from Dusseldorf and surroundings spontaneous urine
      samples were collected on day 108 to day 144 of life and analyzed for the content
      of iodine and creatinine. 26 babies were breast fed. 23 babies received an
      iodized hypoallergenic formula and 26 babies different commercial formulas only
      partly iodized. From 4 parameters to estimate iodine supply of the babies
      (urinary iodine concentration microgram/dl, iodine/creatinine ratio microgram/g;
      estimated daily iodine excretion microgram/d, estimated daily iodine excretion
      corrected for body surface area microgram/dl 1.73 m2) estimated daily iodine
      excretion was the most useful parameter. Breast fed babies showed a significantly
      lower estimated daily iodine excretion (median 32 microgram/d) than babies fed
      the hypoallergenic (52 microgram/d) or a commercial formula (54 micrograms/d). In
      Germany with an insufficient iodine supply of pregnant and lactating mothers
      breast fed infants run a risk for an insufficient iodine supply. Furthermore,
      supplementation of infant formulas with iodine started in 1990/1991 proved to be
      a sufficient measure to correct iodine deficiency.

PMID- 8309207
TI  - [Serum uric acid concentration and anticonvulsant therapy in childhood].
AB  - In antiepileptic treated adults a decrease of serum uric acid concentration was
      reported. In contrast to these findings we did not find a general decrease of
      uric acid concentration in 233 studied epileptic children and juveniles treated
      with antiepileptic drugs. But we found a significant decrease of uric acid
      concentration in epileptic children and juveniles treated with carbamazepine in
      monotherapy as well as in combined treatment. Rather increased uric acid serum
      concentration were found in primidone and valproate monotherapy. In the studied
      age groups only carbamazepine seems to be able to diminish uric acid
      concentration. The underlying mechanisms are unknown.

PMID- 8309208
TI  - [Bromism or chronic bromide poisoning].
AB  - Bromism, the chronic intoxication with bromide is rare and has been almost
      forgotten. In the recent past bromide is rediscovered as an anticonvulsive drug.
      The increasing frequency of bromism in children coming to admission induced this
      report. We describe the cause, the symptoms and the pseudohyperchloremia
      associated with bromism. If unclarified neurological or psychiatric symptoms are
      associated with the determination of an elevated serum chloride concentration and
      a diminished anion gap chronic intoxication with bromide has to be excluded.

PMID- 8309209
TI  - [Use of recombinant tissue plasminogen activator (rt-PA) in occluding thrombosis
      of a Hickman catheter after bone marrow transplantation: clinical and coagulation
      physiologic aspects].
AB  - A 12 year-old female patient suffering from multifocal Ewing's Sarcoma underwent
      bone marrow transplantation in March 1992. The donor was the patient's HLA
      identical brother. On day 38 following BMT, an occluding catheter thrombosis of
      the superior vena cava was diagnosed. Lysis therapy using rt-PA was initiated.
      During therapy, serious bleeding occurred and administration was temporarily
      discontinued. Normalisation of previously high fibrinogen levels during an acute
      phase reaction was seen concomitantly with systemic fibrin and probably also
      fibrinogen fragments as demonstrated using the Western blot technique. Lysis
      therapy resulted in regained catheter patency, while thrombosis of the superior
      vena cava persisted. The reduction in the need for the transfusion of packed
      thrombocytes following lysis was seen as being a positive result. The use of rt
      PA following BMT should be carefully weighed against the risks and requires
      careful patient observation. Due to the systemic fibrinolytic and
      fibrinogenolytic effects combined with mucositis and thrombocytopenia as a result
      of transplantation therapy, a high risk of bleeding complications seems likely.

PMID- 8309210
TI  - Hair analysis for drugs of abuse: evaluation of analytical methods, environmental
      issues, and development of reference materials.
AB  - Methods for extraction of cocaine, some of its metabolites, morphine, and codeine
      from hair and methods for analyzing the extracts have been investigated. Results
      of these studies have shown that extractions with 0.1N HCl are efficient at
      removing the target compounds from hair and appear to be as effective as
      enzymatic digestions that dissolve the hair. GC/MS with either electron
      ionization or chemical ionization was found to provide accurate and unambiguous
      determinations of the target compounds. Tandem mass spectrometry (MS/MS) also
      provided accurate results when performed on extracts from hair, but results were
      ambiguous when MS/MS was performed on hair segments directly. Environmental
      issues, including the removal of powdered and vapor-deposited cocaine from the
      hair surface and the effect of various hair treatments on the levels of cocaine
      entrapped in hair, have also been investigated. Removal of cocaine deposited on
      hair was incomplete by all approaches tested, making differentiation of hair of
      cocaine users from hair with environmental exposure of cocaine difficult.
      Cocaethylene, a cocaine metabolite believed to be formed in the liver, was found
      in the hair of some cocaine users and may be a good marker for proving drug use.
      Common hair treatments, such as shampoos, conditioners, and peroxide bleaches,
      reduced cocaine levels in a fortified hair material by 60 to 80% after 30
      treatments. Finally, to assist laboratories in evaluating the accuracy of their
      methods, two human hair reference materials with recommended concentrations of
      cocaine, benzoylecgonine, morphine, and codeine determined by GC/MS have been
      developed.

PMID- 8309211
TI  - A novel GC/MS derivatization method for amphetamines.
AB  - Many widely used methods for derivatizing drugs of the amphetamine group for
      GC/MS are problematic. The difficulties with these methods include
      incompatibility with other derivatizing agents, short column life, lack of
      abundant high molecular weight ions, and the potential for interference from
      other drugs. The present procedure is an effort to reduce some of these problems
      by the use of a novel derivatizing agent, N-methyl-N-t-butyldimethylsilyl
      trifluoroacetamide (MTBSTFA). We describe here an MTBSTFA derivatization method
      for amphetamine (AMP) and methamphetamine (MAMP) that leads to stable derivatives
      that are well-separated from potential interferences and features high molecular
      weight fragments suitable for selected ion monitoring. The procedure is linear to
      approximately 3000 ng/mL for both AMP and MAMP and appears to be both precise and
      sensitive. Furthermore, it seems to have no adverse effect on column life.

PMID- 8309212
TI  - Potential use of a radioreceptor assay for the determination of benzodiazepine
      compounds in serum.
AB  - The clinical monitoring and intensive care of patients who have taken an overdose
      of a benzodiazepine require rapid and quantitative methods to assess
      benzodiazepine concentrations in biological fluids. A radioreceptor assay (RRA)
      permits the simultaneous measurement of the benzodiazepine molecules that bind to
      the receptor, providing a total estimate of all pharmacologically active forms of
      the drug(s) (parent drug and active metabolites). This study describes the
      development of an RRA for the determination of benzodiazepine compounds in serum
      using a lyophilized bovine brain cerebral cortex receptor preparation. The
      standard curves and the sensitivity of this RRA are determined for 20 different
      benzodiazepines and the specific antagonist flumazenil. The sensitivity ranges
      from 5 ng/mL for clonazepam to 3500 ng/mL for chlordiazepoxide. The IC50 values
      are significantly correlated (r = 0.81) with the lowest recommended therapeutic
      concentrations. The advantages and disadvantages of this RRA are discussed and
      compared with those of other chromatographic and immunological methods.

PMID- 8309213
TI  - Determination of meprobamate in human plasma, urine, and hair by gas
      chromatography and electron impact mass spectrometry.
AB  - A sensitive and specific quantitative assay for the determination of meprobamate
      in human fluids and hair is described. Meprobamate and an internal standard,
      vinylbarbital, are isolated by acid extraction and methylated by derivatization.
      The final extract is separated on a 12-m capillary column HP-1 and drugs are
      detected by selected ion monitoring at m/z 162 and m/z 182 for meprobamate and
      the internal standard, respectively. Applications in forensic science,
      particularly for hair analysis, are presented.

PMID- 8309214
TI  - Detection of paraquat-induced in vivo lipid peroxidation by gas
      chromatography/mass spectrometry and high-pressure liquid chromatography.
AB  - The cyclic oxidation-reduction of paraquat results in the formation of oxygen
      free radicals, which are believed to mediate the toxic manifestations of this
      herbicide. Because of paraquat's profound effects on lipid peroxidation, the
      effect of oral administration of 75 mg paraquat/kg to rats has been examined on
      the urinary excretion of the lipid metabolites malondialdehyde (MDA),
      formaldehyde (FA), acetaldehyde (ACT), and acetone (ACON) over 48 hours post
      treatment. The urinary metabolites were identified by gas chromatography/mass
      spectrometry and quantitated by high-pressure liquid chromatography. Time
      dependent increases in the urinary excretion of the four metabolites were
      observed after paraquat administration. Over the 48 hours of the study, the
      paraquat-induced urinary excretion of MDA, FA, ACT, and ACON increased by
      approximately 218, 155, 331, and 995%, respectively, relative to control animals.
      The data were expressed in nmol/kg body weight/4.5 h. The results clearly
      demonstrate that paraquat increases the urinary excretion of four lipid
      metabolites, which may have widespread applicability as biomarkers of altered
      lipid metabolism in disease states and cases of exposure to environmental
      pollutants and xenobiotics that induce enhanced lipid peroxidation.

PMID- 8309215
TI  - Determination of chloroform levels in blood using a headspace capillary gas
      chromatographic method.
AB  - Headspace (HS) capillary gas chromatography with flame-ionization detection was
      developed for the determination of chloroform levels in blood. Separation of
      chloroform was improved significantly using a DB-WAX capillary column, without
      interference by other volatile substances. Sensitivity was increased by adjusting
      the splitter ratio to 20, without any decline in peak resolution. The HS
      conditions, a 50 degrees C incubation for 30 min, gave reproducible and sensitive
      determinations. The distribution coefficient (k) was calculated to be 8.24. The
      CV was 1.8% for 27.7 micrograms/mL chloroform, and the detection limit was 0.02
      microgram/mL (S/N = 4) when the splitter ratio was 10. Raising HS temperature
      resulted in a significant decrease in k for chloroform in the absence of blood,
      in contrast to the relatively small effect seen in the presence of blood.
      Although inorganic salts showed a salting-out effect, erythrocytes and
      hydrophobic compounds, such as detergent and lipid, significantly suppressed the
      vaporization of chloroform. Chloroform was found to be distributed mainly in
      erythrocytes when incubated with blood overnight at 2 degrees C.

PMID- 8309216
TI  - Pitfalls and solutions in the development of a fully automated solid-phase
      extraction method for drug screening purposes in plasma and whole blood.
AB  - A fully automated solid-phase extraction (SPE) method for drug screening is
      described. The extraction of 19 toxicologically relevant drugs from pretreated
      plasma and pretreated whole blood was accomplished automatically by a Gilson
      ASPEC system equipped with disposable 2.8-mL Bond Elut Certify columns. The
      automated extraction procedure includes 11 fundamental steps: column
      preconditioning; sample application; column washing; pH adjustment; elution of
      drugs by two eluents, which were collected into two separated tubes; addition of
      the chromatographic standard solution; and several SPE column rack movement
      steps. After evaporation, the drugs were quantitated by gas chromatography. Water
      was chosen as the transfer liquid in the ASPEC system because it was cheap and,
      more importantly, because it caused no protein precipitation problem. The effects
      of the sample and eluent flow rates were investigated, and it was found that low
      flow rates were necessary to recover the drugs maximally. In the study, the
      optimal flow rates of sample application, acetone-chloroform elution, and
      ammoniated ethyl acetate elution were 1.5, 0.72, and 0.33 mL/min, respectively.
      The absolute recoveries of 19 drugs from whole blood exceeded 82%, with relative
      standard deviations less than 5% at 2 micrograms/mL.

PMID- 8309217
TI  - Urinary screening for adinazolam and its major metabolites by the Emit d.a.u. and
      FPIA benzodiazepine assays with confirmation by HPLC.
AB  - Adinazolam is a triazolobenzodiazepine, currently under clinical investigation,
      that possesses antidepressant and anxiolytic activity. It has a short half-life
      (less than 3 h), and less than 2% of an oral dose is excreted unchanged. The
      major urinary metabolite is N-desmethyladinazolam, and minor metabolites are
      estazolam and alpha-OH-alprazolam. The objective of this study was to
      characterize the reactivity of adinazolam, N-desmethyladinazolam, and estazolam
      in the Emit d.a.u. benzodiazepine assay and the Abbott TDx urine (FPIA)
      benzodiazepine assay. N-desmethyladinazolam and estazolam gave an equivalent
      response to the Emit cutoff calibrator (300 ng/mL) at 100-200 ng/mL, and
      adinazolam gave an equivalent response at 200 ng/mL. By FPIA, N
      desmethyladinazolam and adinazolam had equivalent net polarization values as the
      300-ng/mL low control at 500-1000 ng/mL, and estazolam gave a positive response
      at 300 ng/mL. Six volunteers received single oral doses of 10, 30, and 50 mg of
      adinazolam. Urine specimens (N = 7) were collected from 0 to 36 h post
      administration. By Emit, all urine specimens at all doses were positive from 2 to
      36 h, and all FPIA analyzed specimens were positive from 2 to 24 h. Confirmation
      testing was performed by HPLC by analyzing for N-desmethyladinazolam. All urine
      specimens were confirmed positive for N-desmethyladinazolam (greater than 200
      ng/mL) except for the blank specimens (time = 0) and 7 of 18 specimens collected
      36 h post-administration. In conclusion, both immunoassay screening assays are
      acceptable for detecting the presence of adinazolam in human urine for up to 24 h
      after a single oral dose of 10-50 mg.

PMID- 8309218
TI  - Isolation of benzoylecgonine from urine using solid-phase extraction.
AB  - An improved procedure for the extraction of benzoylecgonine from urine is
      described. The method uses Drug-Clean GC/MS Benzoylecgonine solid-phase
      extraction tubes and a simple extraction protocol to provide high recoveries of
      the analyte while simultaneously decreasing the preparation time.

PMID- 8309219
TI  - Fatal flecainide intoxication.
AB  - Two fatalities resulting from suicidal ingestion of flecainide are described. The
      decedents, ages 33 and 15, were otherwise healthy; both took their mothers'
      medications. In one case, from electrocardiographic data, there was found a high
      grade conduction block with idioventricular rhythm. Blood and tissue samples from
      autopsy were analyzed for flecainide by gas chromatography/nitrogen-phosphorous
      detection and gas chromatography/mass spectrometry. Blood concentrations of 93.7
      and 100 mg/L flecainide were found.

PMID- 8309220
TI  - Three fatal drug overdoses involving bupropion.
AB  - Bupropion is a "second generation" antidepressant agent structurally related to
      the phenethylamines. Postmortem toxicology data are presented from three suicidal
      drug overdoses in which bupropion was detected. In two cases in which bupropion
      was the major toxicology finding, peripheral blood levels of the parent drug were
      4.0 and 4.2 mg/L and total metabolite levels were 15 and 16.6 mg/L. Lethal doses
      in both cases were estimated by history to be less than 10 g.

PMID- 8309221
TI  - High urinary cannabinoids from a hashish body packer.
AB  - A body packer swallowed 39 condoms containing a total of 518 g hashish oil. He
      was arrested on entry into Canada. Two days later, a urine sample was obtained.
      Total cannabinoid concentrations by TDx and Emit II were 10,200 ng/mL and 11,400
      ng/mL, respectively. The concentration of 11-nor-delta 9-tetrahydrocannabinol-9
      carboxylic acid by gas chromatography/mass spectrometry was 1140 ng/mL.

PMID- 8309222
TI  - Lack of formation of methamphetamine-like artifacts by the monoacetates of
      pseudoephedrine and related compounds in the GC/MS analysis of urine extracts.

PMID- 8309223
TI  - Determination of buprenorphine and its dealkylated metabolite in human hair.

PMID- 8309225
TI  - A simple wash procedure for improving chromatography of HFAA derivatized
      amphetamine extracts for GC/MS analysis.

PMID- 8309224
TI  - Prevalence of cocaethylene in the hair of pregnant women.

PMID- 8309226
TI  - In vitro evaluation of an implantable force transducer (IFT) in a patellar tendon
      model.
AB  - A new implantable transducer has been developed for in situ evaluation of
      ligament and tendon forces. Unlike previous devices, this sensor is placed within
      the specimen, minimizing measurement errors due to impingement on surrounding
      soft tissues and bone. In this study, we present the sensor design details as
      well as test results from initial in vitro trials in the goat patellar tendon
      model. Device performance and influence of the device on the specimen were
      evaluated under several loading conditions. In all cases, device output had a
      strong correlation with induced tissue load. Significant variations in device
      performance were only noted at high tissue deformation rates. More extensive
      investigations will be conducted to assess how changes in transducer design might
      alter performance characteristics.

PMID- 8309227
TI  - Application of the joint coordinate system to three-dimensional joint attitude
      and movement representation: a standardization proposal.
AB  - The selection of an appropriate and/or standardized method for representing 3-D
      joint attitude and motion is a topic of popular debate in the field of
      biomechanics. The joint coordinate system (JCS) is one method that has seen
      considerable use in the literature. The JCS consists of an axis fixed in the
      proximal segment, an axis fixed in the distal segment, and a "floating" axis.
      There has not been general agreement in the literature on how to select the body
      fixed axes of the JCS. The purpose of this paper is to propose a single
      definition of the body fixed axes of the JCS. The two most commonly used sets of
      body fixed axes are compared and the differences between them quantified. These
      differences are shown to be relevant in terms of practical applications of the
      JCS. Argumentation is provided to support a proposal for a standardized selection
      of body fixed axes of the JCS consisting of the axis e1 embedded in the proximal
      segment and chosen to represent flexion-extension, the "floating" axis e2 chosen
      to represent ad-abduction, and the axis e3 embedded in the distal segment and
      chosen to represent axial rotation of that segment. The algorithms for the JCS
      are then documented using generalized terminology.

PMID- 8309228
TI  - Three-body segment dynamic model of the human knee.
AB  - In this paper, a two-dimensional, three-body segment dynamic model of the human
      knee is introduced. The model includes tibio-femoral and patello-femoral
      articulations, and anterior cruciate, posterior cruciate, medial collateral,
      lateral collateral, and patellar ligaments. It enables one to obtain dynamic
      response of the knee joint to any one or combination of quadriceps femoris,
      hamstrings, and gastrocnemius muscle actions, as well as any externally applied
      forces on the lower leg. A specially developed human knee animation program is
      utilized in order to fine tune some model parameters. Numerical results are
      presented for knee extension under the impulsive action of the quadriceps femoris
      muscle group to simulate a vigorous lower limb activity such as kicking. The
      model shows that the patella can be subjected to very large transient patello
      femoral contact force during a strenuous lower limb activity even under
      conditions of small knee-flexion angles. The results are discussed and compared
      with limited data reported in the literature.

PMID- 8309229
TI  - A two-dimensional dynamic anatomical model of the human knee joint.
AB  - The objective of this study is to develop a two-dimensional dynamic model of the
      knee joint to simulate its response under sudden impact. The knee joint is
      modeled as two rigid bodies, representing a fixed femur and a moving tibia,
      connected by 10 nonlinear springs representing the different fibers of the
      anterior and posterior cruciate ligaments, the medial and lateral collateral
      ligaments, and the posterior part of the capsule. In the analysis, the joint
      profiles were represented by polynomials. Model equations include three nonlinear
      differential equations of motion and three nonlinear algebraic equations
      representing the geometric constraints. A single point contact was assumed to
      exist at all times. Numerical solutions were obtained by applying Newmark
      constant-average-acceleration scheme of differential approximation to transform
      the motion equations into a set of nonlinear simultaneous algebraic equations.
      The equations reduced thus to six nonlinear algebraic equations in six unknowns.
      The Newton-Raphson iteration technique was then used to obtain the solution. Knee
      response was determined under sudden rectangular pulsing posterior forces applied
      to the tibia and having different amplitudes and durations. The results indicate
      that increasing pulse amplitude and/or duration produced a decrease in the
      magnitude of the tibio-femoral contact force, indicating thus a reduction in the
      joint stiffness.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309230
TI  - A B-spline least-squares surface-fitting method for articular surfaces of
      diarthrodial joints.
AB  - The B-spline least-squares surface-fitting method is employed to create geometric
      models of diarthrodial joint articular surfaces. This method provides a smooth
      higher-order surface approximation from experimental three-dimensional surface
      data that have been obtained with any suitable measurement technique. Akima's
      method for surface interpolation is used to provide complete support to the B
      spline surface. The surface-fitting method is successfully tested on a known
      analytical surface, and is applied to the human distal femur. Applications to
      other articular surfaces are also shown. Results show that this method is
      precise, highly flexible, and can be successfully applied to a large variety of
      articular surface shapes.

PMID- 8309231
TI  - Finite element analysis of the temperature field around two adjacent cryo-probes.
AB  - A finite element code was developed for the analysis of the temperature field
      around two adjacent cylindrical cryo-probes. The two-phase, two-dimensional
      Stefan problem is solved using a moving boundary approach and space-time finite
      elements. Solution of one-cryo-probe problem compared well with an existing
      analytic solution. The two-cryo-probes problem yielded reasonable results. The
      program simulated the nonsymmetric activation of two probes and the merging of
      the two freezing fronts in the case of symmetric activation.

PMID- 8309232
TI  - Reconstruction of experimental hyperthermia temperature distributions:
      application of state and parameter estimation.
AB  - Subsets of data from spatially sampled temperatures measured in each of nine
      experimental heatings of normal canine thighs were used to test the feasibility
      of using a state and parameter estimation (SPE) technique to predict the complete
      measured data set in each heating. Temperature measurements were made at between
      seventy-two and ninety-six stationary thermocouple locations within the thigh,
      and measurements from as few as thirteen of these locations were used as inputs
      to the estimation algorithm. The remaining (non "input") measurements were
      compared to the predicted temperatures for the corresponding "unmeasured"
      locations to judge the ability of the estimation algorithm to accurately
      reconstruct the complete experimental data set. The results show that the
      predictions of the "unmeasured" steady-state temperatures are quite accurate in
      general (average errors usually < 0.5 degrees C; and small variances about those
      averages) and that this reconstruction procedure can yield improved descriptors
      of the steady-state temperature distribution. The accuracy of the reconstructed
      temperature distribution was not strongly affected by either the number of
      perfusion zones or by the number of input sensors used by the algorithm. One
      situation extensively considered in this study modeled the thigh with twenty
      seven independent regions of perfusion. For this situation, measurements from
      ninety-six to thirteen sensors were used as input to the estimation algorithm.
      The average error for all of these cases ranged from -0.55 degrees C to +0.75
      degrees C, respectively, and was not strongly related to the number of sensors
      used as input to the estimation algorithm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309233
TI  - Dynamic behavior analysis of mechanical monoleaflet heart valve prostheses in the
      opening phase.
AB  - In this paper, fluttering behavior of a mechanical monoleaflet tilting disk heart
      valve prostheses during the opening phase was analyzed. The impact between the
      occluder and the guiding strut at the fully open position was included in the
      analysis with a Bjork-Shiley monoleaflet aortic valve. The motion of the valve
      occluder was modeled as a rotating system, and equations were derived by
      employing the moment equilibrium principle. Forces due to lift, drag, gravity,
      and buoyancy were considered as external forces acting on the occluder. The 4th
      order Runge-Kutta method was used to solve the governing equations. The results
      demonstrated that the occluder reaches the steady equilibrium position only after
      damped vibration. Fluttering frequency varies as a function of time after opening
      and is in the range of 8-84 Hz. Valve opening appears to be affected by the
      orientation of the valve relative to gravitational force. The opening velocities
      are in the range of 0.56-1.37 m/sec and the dynamic loads by impact of the
      occluder and the strut are in the range of 60-190 N.

PMID- 8309234
TI  - Determination of principal reynolds stresses in pulsatile flows after elliptical
      filtering of discrete velocity measurements.
AB  - The purpose of this study was to develop a method to accurately determine mean
      velocities and Reynolds stresses in pulsatile flows. The pulsatile flow used to
      develop this method was produced within a transparent model of a left ventricular
      assist device (LVAD). Velocity measurements were taken at locations within the
      LVAD using a two-component laser Doppler anemometry (LDA) system. At each
      measurement location, as many as 4096 realizations of two coincident orthogonal
      velocity components were collected during preselected time windows over the pump
      cycle. The number of realizations was varied to determine how the number of data
      points collected affects the accuracy of the results. The duration of the time
      windows was varied to determine the maximum window size consistent with an
      assumption of pseudostationary flow. Erroneous velocity realizations were
      discarded from individual data sets by implementing successive elliptical filters
      on the velocity components. The mean velocities and principal Reynolds stresses
      were determined for each of the filtered data sets. The filtering technique,
      while eliminating less than 5 percent of the original data points, significantly
      reduced the computed Reynolds stresses. The results indicate that, with proper
      filtering, reasonable accuracy can be achieved using a velocity data set of 250
      points, provided the time window is small enough to ensure pseudostationary flow
      (typically 20 to 40 ms). The results also reveal that the time window which is
      required to assume pseudostationary flow varies with location and cycle time and
      can range from 100 ms to less than 20 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309235
TI  - An experimental study of pulsatile pipe flow in the transition range.
AB  - The study of pulsatile flows is relevant to many areas of applications. Typical
      applications include aerodynamics, biofluid mechanics, wind flows, and gas
      transport. Transition to turbulence during pulsatile flow is physiologically and
      clinically important. It has been suggested as a possible mechanism to enhance
      the transport of gases during high-frequency ventilation, may be related to
      valvular regurgitation and heart murmurs and to post stenotic dilatation and
      aneurysms. Measurements in a pulsatile pipe flow with a superimposed mean flow
      are reported. Data were taken in a water flow with mean Reynolds numbers in the
      range of 0 < Re(m) < 3000, oscillating Reynolds numbers of 0 < Re omega < 4000,
      and Stokes parameter 7 < lambda < 15. Velocity profiles of various phases of the
      flow, condition for flow reversal, and pressure losses were measured. The
      adequacy of a quasi-steady-state model is discussed. Condition for transition is
      determined by visually inspecting velocity signals at the centerline.

PMID- 8309236
TI  - An experiment on the pulsatile flow at transitional Reynolds numbers--the fluid
      dynamical meaning of the blood flow parameters in the aorta.
AB  - An experiment on the fully developed sinusoidal pulsatile flow at transitional
      Reynolds numbers was performed to evaluate the basic characteristics of the wall
      shear stress. In this experiment, the wall shear stress was calculated from the
      measured section averaged axial velocity and the pressure gradient by using the
      section averaged Navier-Stokes equation. The experimental results showed that the
      ratio of the amplitude of the wall shear stress to the amplitude of the pressure
      gradient had the maximum value when the time averaged Reynolds number was about
      4000 and the Womersley number was about 10. As this condition is close to the
      blood flow condition in the human aorta, it is suggested that the parameter of
      the aorta has an effect to increase the amplitude of the wall shear stress acting
      on the arterial wall.

PMID- 8309237
TI  - Steady flow in abdominal aortic aneurysm models.
AB  - Steady flow in abdominal aortic aneurysm models has been examined for four
      aneurysm sizes over Reynolds numbers from 500 to 2600. The Reynolds number is
      based on entrance tube diameter, and the inlet condition is fully developed flow.
      Experimental and numerical methods have been used to determine: (i) the overall
      features of the flow, (ii) the stresses on the aneurysm walls in laminar flow,
      and (iii) the onset and characteristics of turbulent flow. The laminar flow field
      is characterized by a jet of fluid (passing directly through the aneurysm)
      surrounded by a recirculating vortex. The wall shear stress magnitude in the
      recirculation zone is about ten times less than in the entrance tube. Both wall
      shear stress and wall normal stress profiles exhibit large magnitude peaks near
      the reattachment point at the distal end of the aneurysm. The onset of turbulence
      in the model is intermittent for 2000 < Re < 2500. The results demonstrate that a
      slug of turbulence in the entrance tube grows much more rapidly in the aneurysm
      than in a corresponding length of uniform cross section pipe. When turbulence is
      present in the aneurysm the recirculation zone breaks down and the wall shear
      stress returns to a magnitude comparable to that in the entrance tube.

PMID- 8309238
TI  - Bolus contaminant dispersion in oscillatory tube flow with conductive walls.
AB  - Dispersion of a bolus contaminant in a straight tube with oscillatory flows and
      conductive walls is solved by using a derivative-expansion method. Using
      asymptotic methods when small conductance exists, the axial dispersion, as
      measured by the time-averaged effective diffusivity, increases over the insulated
      case, as long as the dimensionless frequency (Womersley parameter), alpha, is
      smaller than a critical value. When alpha exceeds this value, axial dispersion is
      diminished by wall conductance. The functional dependence of this critical alpha
      on the system parameters is investigated. We examine the radial wall transport
      both for total mass and localized flux, which is found to be independent of
      velocity field, and compute the time-dependent total mass of wall transport and
      asymptotic Sherwood number for large times as a function of the wall conductance.

PMID- 8309239
TI  - Collapse of thin-walled elliptical tubes for high values of major-to-minor axis
      ratio.
AB  - The topic of this study concerns principally representative models of some
      elliptical thin-walled anatomic vessels and polymeric tubes under uniform
      negative transmural pressure p (internal pressure minus external pressure). The
      ellipse's ellipticity k(o), defined as the major-to-minor axis ratio, varies from
      1 up to 10. As p decreases from zero, at first the cross-section becomes somewhat
      oval, then the opposite sides touch in one point at the first-contact pressure
      pc. If p is lowered beneath pc, the curvature of the cross-section at the point
      of contact decreases until it becomes zero at the osculation pressure or the
      first line-contact pressure pl. For p < pl, the contact occurs along a straight
      line segment, the length of which increases as p decreases. The pressures pc and
      pl are determined numerically for various values of the wall thickness of the
      tubes. The nature of contact is especially described. The solution of the related
      nonlinear, two-boundary-values problem is compared with previous experimental
      results which give the luminal cross-sectional area (from two tubes), and the
      area of the mid-cross-section (from a third tube).

PMID- 8309240
TI  - A finite difference heat transfer analysis of a percutaneous transluminal
      microwave angioplasty system.
AB  - Finite difference time domain (FDTD) techniques have been developed to calculate
      the specific absorption rates (SAR) in hyperthermia models. The University of
      Utah Hyperthermia Research Group has extended these numerical techniques for
      developing a percutaneous transluminal microwave angioplasty applicator,
      calculating the SARs produced by a high energy electromagnetic field to remove
      atherosclerotic plaques in blood vessels. The objective of this research was to
      derive a method for calculating the bioheat transfer in biological tissue
      surrounding a microwave angioplasty applicator. A hypothetical model was
      developed and observations are discussed based on the numerical results of this
      study. A limited analysis on the thermal effects of microwave pulsing was also
      completed. Preliminary numerical calculations yielded reasonable results.
      Experimental laboratory tests are required to validate the accuracy of the
      numerical results found in this study. Further development of this thermal
      analysis method may greatly assist in future studies of new applicator
      configurations to ensure safe atherosclerotic plaque removal and to predict the
      resulting thermal environments.

PMID- 8309241
TI  - Effects of rehydration state on the flexural properties of whole mouse long
      bones.
AB  - The effects of bone water content during dehydration and rehydration on the
      flexural properties of whole mouse femora were evaluated using three-point
      bending. The elastic and plastic flexural properties of the bones were determined
      on a dry mass normalized basis over dehydration times ranging from 0.25 to 48.0
      hr; and (following complete dehydration) rehydration times ranging from 0.08 to
      12.0 hr. Bones stored in physiological saline for times < 1 hr served as the
      control group. As expected, dehydration produced increased stiffness and strength
      along with decreased ductility. Upon rehydration, a statistically significant
      linear dependence of mechanical properties on recovered free water was obtained
      for all parameters except the maximum load. Elastic mechanical properties
      comparable to the controls were regained at differing rates and levels of
      recovered water content; however, after 3 hr of rehydration there were no
      statistically significant differences with respect to the control values. The
      results of this study indicate that the original flexural properties of whole
      mouse femora are preserved by air dehydration and can be recovered using
      appropriate saline rehydration intervals.

PMID- 8309242
TI  - The concept of profession and professional ethics.

PMID- 8309243
TI  - The differential diagnosis of white lesions resembling oral hairy leukoplakia.

PMID- 8309244
TI  - Microleakage of glass ionomer cement and composite resin restorations in cut non
      retentive preparations and pre-existing cervical erosion/abrasion lesions.

PMID- 8309245
TI  - Modulation of intracellular metabolism of cytosine arabinoside in acute myeloid
      leukemia by granulocyte-macrophage colony-stimulating factor.
AB  - The current study investigated the effect of granulocyte-macrophage colony
      stimulating factor (GM-CSF) on the intracellular metabolism and cytotoxicity of 1
      beta-D-arabinofuranosylcytosine (araC) in leukemic cells of 45 patients with
      acute myeloid leukemia (AML). AML blasts from bone marrow (BM) (n = 39) and
      peripheral blood (PB) (n = 17) were incubated for 48 h with or without GM-CSF
      (100 U/ml) followed by a concurrent treatment with increasing concentrations of
      araC (0.06-100 microM) for an additional 24 h. After GM-CSF a 1.5-8.4-fold
      (median 2.3) increase in 3H-araC incorporation into the DNA was observed in ten
      of 14 peripheral blast specimens and in 23 of 28 bone marrow samples, 18 of whom
      also showed an enhanced 3H-TdR incorporation (1.5-8.5-fold, median 2.0-fold).
      Four different types of response were identified when analyzing 3H-araC
      incorporation into the DNA of bone marrow samples in relation to the applied araC
      dose: (i) 8/28 cases had increases of the araC incorporation at all araC dose
      levels applied (0.06-100 microM), (ii) 12/28 at low araC concentrations only
      (0.06-1.0 microM), (iii) 3/28 at high araC concentrations only (10-100 microM),
      and (iv) 5/28 showed no increase at any dose level given. Hence, 20 of the 23
      responding patients revealed a GM-CSF induced enhancement of araC incorporation
      at low or conventional doses of araC (0.06-1.0 microM). Fourteen of the 18 cases
      with concomitant rises of 3H-TdR and 3H-araC incorporation into the DNA after GM
      CSF had elevated DNA polymerase alpha activity (16-531%, median 72%) and in ten
      cases overall DNA polymerase activity was enhanced (10-70%, median 22.5%). In
      contrast, thymidine kinase (TK) and deoxycytidine kinase (dCK) activity were
      elevated after GM-CSF in only ten and five patients, respectively. An increase in
      the fraction of cells in S phase was found in 11/21 bone marrow specimens and in
      5/9 peripheral blast samples. However, no correlation was observed between
      increases in the proportion of cells in S phase and enhancements in enzyme
      activities. In 13 cases the cytotoxicity of araC with and without GM-CSF was
      assessed by means of a blast cell colony assay. Preincubation with GM-CSF
      increased the araC mediated cytotoxicity in ten of 13 patients by a median of 3.2
      fold (range 2.2-229-fold). The respective LD50 values for araC were reduced from
      0.45 to 0.19 microM on average.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8309246
TI  - Human trithorax gene rearrangements in therapy-related acute leukaemia after
      etoposide treatment.
AB  - Molecular analysis of leukaemic blasts from 9 patients with secondary myeloid
      leukaemia reveals rearrangements of the human trithorax gene (Htrx-1) in three
      patients, including one in whom abnormalities of chromosome 11 band q23 were not
      detected by conventional cytogenetics. All three patients had been treated with
      epipodophyllotoxins, whilst none of the six without rearrangements had received
      these agents. The patients with rearrangements also presented with different
      clinical features. These findings support the separation of secondary leukaemia
      into two classes, and correlate rearrangements of the Htrx-1 gene with a group of
      secondary leukaemias that follow specific cancer treatment regimens.

PMID- 8309247
TI  - Calcitonin gene methylation in chronic myeloproliferative disorders.
AB  - Alterations in DNA methylation appear to be an integral part of the malignant
      transformation. For example, the p15 region of chromosome 11 with multiple genes
      related to cell growth regulation exhibits different methylation patterns in the
      5' area of the calcitonin A gene in healthy bone marrow cells, and in leukemic
      cell populations. In this work the methylation status of the 5' area of the
      calcitonin gene in myeloproliferative disorders (MPD) other than chronic myeloid
      leukemia (CML) is studied. A total number of 37 patients with polycythemia vera,
      essential thrombocythemia, or myelofibrosis were studied. A control group of 18
      healthy persons and patients with reactive hematologic changes was included. The
      DNA isolated from peripheral blood or bone marrow cells was digested with the
      methylation-sensitive HpaII restriction enzyme. A Southern blot was hybridized
      with a 1.7 kb probe specific to the 5' area of the calcitonin gene. The result
      was visualized autoradiographically and analyzed with a densitometer. The results
      have been expressed as ratios between the abnormal and normal autoradiography
      band intensities, referred to as the calc-value or CALC. An increase in the calc
      value signifies increasing methylation. In the control group the calc-value had a
      mean of 0.274. The myelofibrosis patients exhibited very strong hypermethylation
      in the calcitonin gene 5' area, with a mean calc-value of 11.1 (median 2.6). The
      polycythemia vera patients showed considerable variation in their methylation
      status, with a mean value of 1.52. The essential thrombocythemia patients
      exhibited weak hypermethylation, with a mean calc-value of 0.58. A correlation
      between karyotypic abnormalities and hypermethylation was observed. Complicated
      forms of MPD exhibited higher levels of methylation than the uncomplicated
      disease forms.

PMID- 8309248
TI  - A hematopoietic protein tyrosine phosphatase (HePTP) gene that is amplified and
      overexpressed in myeloid malignancies maps to chromosome 1q32.1.
AB  - Tyrosine phosphorylation is an important regulator of cell growth and
      differentiation reflecting the interaction of protein tyrosine kinases (PTK) and
      protein tyrosine phosphatases (PTP). Although excessive PTK activity can result
      in hematopoietic cell transformation, perturbation of either of these two
      modulators may result in uncontrolled cell growth. Myeloid cells are responsive
      to growth factors and cytokines that induce tyrosine phosphorylation and can
      become ligand independent when endogenous PTKs become dysregulated. Specific
      PTPs, through mutation or altered expression, may enhance PTK activities and also
      cause myeloid ligand independence, though this has not yet been demonstrated. We
      have previously reported the isolation of a hematopoietic specific cytoplasmic
      PTP (HePTP). We now report that this gene maps to chromosome 1q32.1 utilizing
      fluorescent in situ chromosomal hybridization (FISH). This site is frequently
      amplified in preleukemic myeloproliferative diseases. FISH analysis of a patient
      with myelodysplastic syndrome characterized by myeloid hypoplasia and monocytosis
      reveals triplication of the HePTP gene on one allele with elevated protein
      expression in neoplastic myelomonocytic cells. Elevated expression is also
      identified in blasts from some patients with acute leukemia. These observations
      prompted us to examine the experimental effects on cell growth of HePTP
      overexpression. Though normal myeloid cells show minimal HePTP expression, all
      hematopoietic cell lines tested show high expression of HePTP. Gene transfer of
      HePTP into NIH 3T3 cells was therefore performed, which caused altered cell
      morphology, disorganized growth, anchorage independent colony formation and
      subtle differences in the pattern of tyrosine phosphoproteins compared to control
      cell lines. We conclude that amplification and overexpression of HePTP may be an
      important cofactor contributing to abnormal myeloid cell growth.

PMID- 8309249
TI  - Recurrent cytogenetic abnormalities observed in complete remission of acute
      myeloid leukemia do not necessarily mark preleukemic cells.
AB  - We have undertaken the cytogenetic monitoring of 39 adult patients treated for de
      novo acute myeloid leukemia (AML) by intensive chemotherapy. We describe this
      monitoring in seven patients in continuous complete clinical and morphologic
      remission (CR) of AML. Although in CR, these patients exhibit the emergence of
      cytogenetically abnormal clones. Abnormalities observed include monosomy 7,
      del(20)(q11), partial trisomy 1q, and 6p12-22 rearrangements. They correspond to
      well-known chromosomal rearrangements commonly found in myelodysplasia (MDS), and
      myeloproliferative syndromes (MPS), as well as AML. Present as the sole detected
      chromosomal change, they preceded by months the onset of overt leukemia or MDS.
      In some cases, the abnormal clone showed a proliferative advantage (some patients
      exhibited up to 100% of abnormal bone marrow metaphases in subsequent analyses).
      AML relapse, when it occurred, was associated with a different chromosomal
      modification. Altogether the question arises, whether the abnormalities pointed
      out in our study (monosomy 7, del(20)(q11), partial trisomy for the long arm of
      chromosome 1 (q21qter), 6p12-22 rearrangements), and seen after chemotherapy,
      mark preleukemic cells or not, and whether they participate indirectly, or not at
      all in the leukemic process.

PMID- 8309250
TI  - Resistance to cytosine arabinoside in acute leukemia: the significance of
      mutations in CTP synthetase.
AB  - The molecular events which confer cellular resistance to cytotoxic drugs such as
      cytosine arabinoside (ara-C) are poorly understood. Nevertheless, in a proportion
      of patients with acute leukemia, such events will be responsible for the failure
      of therapy. Mutations which cause ara-C resistance in a chinese hamster ovary
      (CHO) cell model have been identified as regulatory base substitutions, occurring
      in specific sites of the gene coding for an enzyme critical in pyrimidine
      metabolism, CTP synthetase (CTPs). These cells have elevated dCTP pools, a
      feature common to biochemical studies of other ara-C resistant leukemic cells. A
      94% homology exists between the hamster and human ctps genes. In this study,
      similar mutations were sought in samples taken from 36 patients, with recurrent
      or resistant acute leukemia. No mutations were identified in the regions
      indicated by the CHO model using techniques capable of detecting mutations only
      if present in more than 10% of the cells studied. Thus, mutations in these sites
      within the human ctps gene do not appear to be a major mechanism of resistance to
      ara-C in acute leukemia. Further studies should be directed towards developing
      more sensitive methods of detection, and these then applied both to CTPs and to
      other enzymes involved in pyrimidine metabolism.

PMID- 8309251
TI  - Selective inhibition of primary acute myeloid leukaemia cell growth by
      lovastatin.
AB  - Primary human acute myeloid leukaemic (AML) cells from bone marrow (BM) and
      peripheral blood (PB), the human myeloblastic leukaemia cell line (HL60) and
      normal human BM mononuclear cells were cultured in serum-free medium. The
      survival of progenitor cells from normal BM, HL60 and AML cell populations was
      reduced over a range of concentrations of lovastatin. This dose response
      relationship was more pronounced in HL60 and AML cell cultures, indicating
      greater sensitivity of AML progenitor cells compared with normal BM progenitors.
      Short-term exposure (18 h) to a range of concentrations of lovastatin showed the
      same differential response between leukaemic and normal BM cells in terms of
      clonogenicity. At a concentration of 10 micrograms/ml progenitor cell survival
      remained above 65% for normal BM while at this concentration leukaemia progenitor
      cell survival fell below 25% of the untreated values. The differential effect of
      lovastatin on normal and leukaemic progenitor cells may have value in the
      clinical management of AML. The possible use of lovastatin, or related drugs, as
      adjuvants to conventional chemotherapy including in vitro BM purging, merits
      consideration.

PMID- 8309252
TI  - Molecular heterogeneity of variant Philadelphia translocations in childhood acute
      lymphoblastic leukaemia.
AB  - In acute lymphoblastic leukemia (ALL), it is unclear whether variant Philadelphia
      (Ph) translocations have the same molecular and clinical implications as the
      classical translocation. Two children with Ph+ ALL with variant translocations
      are described. One, in whom cytogenetic remission was not achieved, had evidence
      of translocation of c-abl to chromosome 22, rearrangement of minor breakpoint
      cluster region (mBCR) and expression of hybrid bcr/abl transcripts. In the other
      case, no gene rearrangement was found and complete remission was achieved.
      Variant Ph translocations in childhood ALL are heterogeneous at the molecular
      level. Molecular studies coupled with observations of clinical outcome are needed
      in larger numbers of such children to determine whether poor clinical response
      correlates with bcr/abl involvement and to allow planning of appropriate
      therapeutic strategies.

PMID- 8309253
TI  - Polymerase chain reaction amplification analyses of clonality in T-cell
      malignancy including peripheral T-cell lymphoma.
AB  - Clonality in T-cell malignancy was investigated using T-cell receptor (TcR) V
      beta 1-20 family primers and polymerase chain reaction amplification (PCR) of
      cDNA prepared from tissue biopsies and blood involved with tumour. Secondary PCR
      amplification of the VDJ joints of primary PCR products was performed to
      distinguish clonal from polyclonal products, and clonal V beta gene products were
      confirmed by direct PCR sequencing in the majority of cases. In eight T-cell
      malignancies including T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell
      chronic lymphocytic leukaemia (T-CLL) shown to be clonal by Southern blot
      analysis, one or two primary PCR products were identified and shown to be clonal.
      In five cases of peripheral T-cell lymphoma (PTCL) all V beta 1-20 families were
      identified after primary PCR amplification, and clonal products were identified
      in two cases after secondary amplification; TcR V beta clonal families could not
      be demonstrated in the remaining three cases. These data were in agreement with
      previous Southern blot analysis of these cases, and confirmed the presence of
      reactive T cells in PTCL as well as providing further evidence for the genotypic
      heterogeneity of this entity. In the remaining case, a blood lymphocytosis,
      primary PCR amplification produced predominant TcR V beta 6 and V beta 12 family
      products, of which the V beta 6 family proved clonal after secondary PCR
      amplification. There was no evidence for overrepresentation of TCR V beta
      families by the tumour populations in this study, furthermore the data confirm
      the involvement of reactive cells in T-cell malignancy and the genetic
      heterogeneity of PTCL.

PMID- 8309254
TI  - Differential expression of collagenase by human fibroblasts and bone marrow
      stromal cells.
AB  - The bone marrow stroma, represented in long-term marrow culture by cells of the
      adherent layer, is composed of a heterogenous mixture of macrophages and
      mesenchymal cells, including fibroblasts, endothelial cells and adipocytes, in
      association with a proteoglycan matrix. This matrix, which is synthesized by the
      stroma, is capable of binding hematopoietic growth factors, and likely plays a
      major role in hematopoietic regulation. Clonally-derived non-transformed bone
      marrow stromal cells, propagated in the presence of basic fibroblast growth
      factor, were studied for expression of collagenase, an enzyme whose substrate,
      collagen, is a major component of the extracellular matrix. Expression of steady
      state collagenase mRNA was undetectable in both unstimulated dermal fibroblasts
      and non-transformed marrow stromal cells. However, stimulation with interleukin 1
      alpha (10 U/ml) for 24 h resulted in marked accumulation of collagenase mRNA in
      dermal fibroblast cells, yet failed to elicit a similar response in bone marrow
      stromal cells. Both marrow stromal cells and dermal fibroblasts constitutively
      expressed transcripts of collagen I, and rhIL-1 alpha upregulated transcripts of
      interleukin 6 in both these cells as well. Although similar in morphology, these
      data indicate that bone marrow stromal cells differ from fibroblasts in their
      response to IL-1. In the marrow microenvironment, where IL-1 may be secreted by a
      variety of cell types, such suppression of collagenase expression may serve to
      prevent unwanted mobilization of collagen from the glycoprotein matrix by marrow
      stromal cells.

PMID- 8309255
TI  - A novel chromosomal abnormality detected in a case of acute myelomonocytic
      leukemia.
AB  - A not yet recorded translocation, t(3:17)(q21;q23), detected in a case of acute
      myelomonocytic leukemia, is reported. In spite of an aggressive cytotoxic
      chemotherapy, the disease showed a rapid fatal course, confirming the dismal
      prognostic significance of structural, 'primary' chromosomal abnormalities in
      acute leukemias.

PMID- 8309256
TI  - Poor response to all-trans retinoic acid therapy in a t(11;17) PLZF/RAR alpha
      patient.
AB  - All-trans retinoic acid (ATRA) is a potent inducer of differentiation and cell
      death in malignant cells. Its effect is known to be mediated through binding to
      specific nuclear (RARs and RXRs) or cytoplasmic (CRABP) proteins. ATRA is
      strikingly effective in acute promyelocytic leukemia (the AML3 subtype) inducing
      a high incidence of complete remissions. Paradoxically, most AML3 cells harbor an
      abnormal retinoic acid receptor (PML/RAR alpha) resulting from the t(15;17)
      translocation. Though few AML3 patients do not respond to ATRA therapy,
      individualization of these cases is of practical importance. Recently the RAR
      alpha gene has been demonstrated to be involved in a novel fusion transcript
      (PLZF/RAR alpha) through a t(11;17) translocation. We describe here the second
      case of such a patient with a t(11;17)-PLZF/RAR alpha leukemic clone. Southern
      analysis revealed that the breakpoint in the RAR alpha gene was within the second
      intron (as for PML/RAR alpha) and the intron separating the second and third zinc
      finger of the PLZF gene. In vitro, the leukemic cells did not show increased NBT
      reduction or loss of self-renewal after incubation with ATRA. After therapy with
      ATRA, only partial remission was obtained. These results suggest that the
      t(11;17) (PLZF/RAR alpha) case of this study was less responsive to ATRA therapy
      than t(15;17) (PML/RAR alpha) cases and raises the question of the definition of
      this novel AML subtype.

PMID- 8309257
TI  - Simultaneous progressive multifocal leukoencephalopathy, Epstein-Barr virus (EBV)
      latent infection and cerebral parenchymal infiltration during chronic lymphocytic
      leukemia.
AB  - We report a non-HIV patient who had B chronic lymphocytic leukemia (CLL) with
      progressive multifocal leukoencephalopathy (PML) and diffuse cerebral leukemic
      parenchymal infiltration in the presence of JC virus and Epstein-Barr virus (EBV)
      cerebral co-infection. Multiple subcortical hypodensities lining the cortico
      subcortical junction were present within the white matter on computerized
      tomography (CT) scan, with large areas of high signal intensity on T2-weighted
      sequences on magnetic resonance imaging (MRI). JCV DNA was identified in
      peripheral blood nuclear cells and cerebrospinal fluid polymerase chain reaction
      (PCR) DNA/DNA hybridization plus Southern blot analysis. Frontal stereotactic
      biopsy confirmed the diagnosis of PML by immunocytochemistry, in situ
      hybridization (ISH) with JC Enzo probe and electron microscopy. Leukemic B cells
      with the same phenotype as leukemic blood cells were disseminated in the
      demyelinated areas. They were labeled by anti-latent membrane protein and by
      BamHl W EBV probe after ISH. Adhesion and activation molecules were positive for
      CD23. Autopsy showed diffuse visceral leukemic infiltration without acutization.
      EBV-transformed B lymphocytes would favour JCV penetration and/or intracerebral
      reactivation of previously latent JCV infection with further development of
      simultaneous PML and cerebral CLL infiltration in an immunosuppressed patient.

PMID- 8309258
TI  - Sensitivity of different methods for the detection of myeloperoxidase in leukemia
      cells.
AB  - We examined the sensitivity of different myeloperoxidase (MPO) detection methods
      in leukemia cell lines. To this end the MPO-positive acute promyelocytic leukemia
      cell line NB-4 was diluted into cell populations of the MPO-negative myeloma cell
      line MM-1 at different ratios. MPO protein was identified by classical
      cytochemical staining and by a specific anti-MPO monoclonal antibody in an
      immunofluorescent reaction. Cytochemical staining detected 1% positive cells
      among 99% negative cells. Careful, but time-consuming observation enabled the
      detection of positive cells in even higher dilutions. At least a 10-fold increase
      in sensitivity was achieved with the immunofluorescent method, as brightly
      fluorescent cells are more amenable for a screening of slides at lower
      microscopic magnification than the cytochemically visualized cells. MPO mRNA
      expression was examined in whole cell populations by Northern blotting (maximal
      sensitivity 1%), a reverse transcriptase-polymerase chain reaction (RT-PCR)
      amplification assay (sensitivity 0.1%), and by RT-PCR followed by Southern
      blotting (sensitivity 0.05%). The high sensitivity of PCR-based techniques is
      offset by the fact that these methods do not allow for the identification and
      further characterization of the individual, MPO-positive cells. Thus, methods
      examining bulk populations require homogeneous cell samples in order to avoid
      false-positivity stemming from a few residual bystander cells. The five different
      techniques were used to determine the status of MPO expression in 20 randomly
      chosen leukemia cell lines of myelomonocytic origin. In 11 cell lines (8 positive
      and 3 negative) all five tests provided concordant results. Three cell lines were
      Northern-negative, but RT-PCR-positive and MPO protein-positive suggesting that
      Northern blot analysis is the least sensitive tool. Six cell lines were devoid of
      MPO protein, at least according to the methods used here, but trace expression of
      MPO message was documented by PCR. All five techniques have advantages and
      drawbacks and must be carefully selected in order to obtain useful data. The
      detection of MPO is of experimental and clinical importance in the distinction of
      myeloid from lymphoid leukemias, and in the lineage assignment of apparently
      biphenotypic or unclassifiable cases.

PMID- 8309259
TI  - Dr. Charles W. Mayo, surgeon and humanitarian.

PMID- 8309260
TI  - Enteric protein loss after the Fontan operation.
AB  - OBJECTIVE: The current study was undertaken to assess the frequency of excessive
      enteric protein loss and protein-losing enteropathy in the relatively early
      period after the Fontan operation. DESIGN: Protein excretion was determined in 26
      of 27 consecutive patients who underwent the Fontan procedure between January and
      June 1990 at the Mayo Clinic. MATERIAL AND METHODS: At two testing intervals
      during the first 4 months after the Fontan operation, alpha 1-antitrypsin
      clearance and fecal alpha 1-antitrypsin concentration studies were done. RESULTS:
      All results were normal for the first postoperative test period (2 to 8 weeks).
      For the second study period, all 17 patients tested had normal alpha 1
      antitrypsin clearances. One of the 17 patients had an appreciably increased fecal
      alpha 1-antitrypsin concentration and transient protein-losing enteropathy.
      CONCLUSION: Excessive enteric protein loss and protein-losing enteropathy are
      relatively uncommon during the first 4 months after the Fontan operation.

PMID- 8309261
TI  - Orbital emphysema: case reports and review of the literature.
AB  - OBJECTIVE: This study was designed to describe the usual clinical findings of
      orbital emphysema as well as unusual and infrequent but important causes of this
      condition. DESIGN: We present seven detailed cases of orbital emphysema and
      review the pertinent English-language literature published since 1900. MATERIAL
      AND METHODS: Characterization of the seven patients with orbital emphysema
      illustrates the various causes and clinical findings of the disorder.
      Additionally, we review 78 previously published cases of orbital emphysema to
      determine the treatment and prognosis of this condition. RESULTS: Trauma is the
      most frequent cause of orbital emphysema; however, orbital emphysema also may
      occur spontaneously or as a complication of pulmonary barotrauma, infection, and
      operation. In most cases, orbital emphysema resolves spontaneously without
      compromising ocular function. If excessive amounts of air accumulate within the
      orbit, however, complications such as occlusion of the central retinal artery or
      compressive optic neuropathy may lead to loss of vision if not recognized
      promptly and treated. CONCLUSION: In most cases, orbital emphysema is an
      incidental, benign finding that resolves with time. Careful observation is the
      only treatment necessary unless an orbital fracture involves an infected sinus,
      in which case prophylactic orally administered antibiotics may be prescribed.

PMID- 8309262
TI  - Tumor-ablative surgery, microvascular free tissue transfer reconstruction, and
      postoperative radiation therapy for advanced head and neck cancer.
AB  - OBJECTIVE: The objectives of this study were to determine whether the combination
      of complex tumor-ablative surgery and microvascular free tissue transfer
      reconstruction delays the onset of postoperative radiation therapy, whether free
      tissue transfers are lost after a course of radiation therapy, and what patterns
      of tumor recurrence and survival rates are present in patients who undergo this
      type of multidisciplinary treatment. DESIGN: A retrospective review was conducted
      in 37 patients who underwent tumor-ablative surgery and reconstruction between
      November 1987 and August 1991. MATERIAL AND METHODS: Of the 30 men and 7 women
      who underwent tumor-ablative surgery, microvascular free tissue transfer
      reconstruction, and postoperative radiation therapy, recurrent or T4 primary
      tumors were treated in 84%. Sixty-two percent of the patients had nodal
      metastatic disease. The median dose of postoperative irradiation was 60 Gy
      (range, 32.4 to 76.8). Follow-up in all patients was until death (21 patients) or
      for a median of 17.5 months (range, 4.1 to 43.2). RESULTS: The median duration of
      overall survival and the 2-year overall survival rate were 17 months and 46%,
      respectively. For cause-specific survival, the median duration and 2-year rate
      were 17 months and 50%, respectively. Local recurrence developed in 8 patients,
      neck recurrence in 10, and distant metastatic disease in 11. No microvascular
      free tissue transfers failed. CONCLUSION: Radiation therapy can begin in most
      patients within 8 weeks postoperatively, microvascular free tissue transfers seem
      to tolerate postoperative radiation therapy well at the doses administered, and
      the rates of local and neck control are reasonable relative to the advanced stage
      of the cancers treated.

PMID- 8309263
TI  - Relative value of transdermal and oral estrogen therapy in various clinical
      situations.
AB  - OBJECTIVE: In this study, we reviewed the comparative effectiveness of
      transdermal and oral estrogen therapy in various groups of women. DESIGN: On the
      basis of published data and personal clinical experience, we compiled
      recommendations for use of the various modes of estrogen replacement therapy.
      MATERIAL AND METHODS: The use of injectable estrogen or implantable estrogen
      pellets can no longer be recommended because of their expense, inconvenience, and
      unphysiologic pattern of serum estrogen response. The two main estrogen
      preparations currently used in the United States--orally administered conjugated
      estrogens and transdermally administered estradiol--undergo different metabolism,
      and these processes are reflected in differing levels of circulating hormones and
      hepatic by-products, including blood clotting factors, binding proteins, renin
      substrate, and apolipoproteins, and in varied composition of the bile. RESULTS:
      At least theoretically, transdermal estrogen therapy might be more beneficial
      than oral estrogen therapy for women who smoke cigarettes or who have migraine
      headaches, hypertriglyceridemia, hepatobiliary disorders, fibrocystic breast
      disease, or a history of thromboembolism. In contrast, women with
      hypercholesterolemia might respond better to oral than to transdermal estrogen
      therapy. CONCLUSION: Additional properly designed clinical studies are necessary
      before these recommendations for estrogen replacement therapy can be validated or
      refuted.

PMID- 8309264
TI  - Julius Axelrod--American biochemist and Nobel Prize winner.

PMID- 8309265
TI  - Immunomagnetic separation of subpopulations of apolipoprotein A-I.
AB  - OBJECTIVE: This study was undertaken to measure the subfractions of high-density
      lipoprotein (HDL) in patients with diabetes or coronary artery disease and in
      normal control subjects. DESIGN: A new immunomagnetic separation technique was
      used to characterize the lipid profile in four groups: (1) control subjects, (2)
      patients with diabetes but no coronary artery disease (CAD), (3) those with CAD
      only, and (4) those with both diabetes and CAD. MATERIAL AND METHODS: To study
      the individual roles of the two discrete HDL subpopulations of particles-
      LpAI/AII (apolipoprotein [apo] A-I associated with A-II) and LpAI (apo A-I
      without A-II)--in lipoprotein metabolism, we developed an immunomagnetic
      separation technique using magnetic beads coated with antibodies to human apo A
      II. The beads bind particles that contain both apo A-II and apo A-I and are
      precipitated by a magnetic field. LpAI levels were measured in the supernatant by
      performing an apo A-I radioimmunoassay. LpAI/AII levels were determined by
      subtracting the LpAI levels from total plasma apo A-I. RESULTS: In comparison
      with control subjects, patients with diabetes, CAD, or both had significantly
      decreased levels of LpAI/AII. LpAI levels were normal in patients with diabetes
      without CAD but significantly lower than control values in those with diabetes
      and CAD. CONCLUSION: Our findings suggest that both subpopulations of HDL
      particles have implications in the development of atherosclerosis in patients
      with and without diabetes.

PMID- 8309266
TI  - Pernicious anemia revisited.
AB  - OBJECTIVE: We discuss the pathophysiologic mechanisms, clinical features,
      diagnosis, and treatment of pernicious anemia (PA). DESIGN: A review of the
      clinical applications of the diagnostic and therapeutic progress of PA is
      presented. MATERIAL AND METHODS: A patient with PA may have a wide range of
      initial complaints that affect various organ systems or may be entirely
      asymptomatic. Hematologic variables may be normal in patients with cobalamin
      (Cbl) deficiency. Because of the difficulties in diagnosing Cbl deficiency,
      alternatives to measuring Cbl have been sought. Determining the urinary
      methylmalonic acid level is a less invasive, more practical, and, possibly, more
      sensitive method. The Schilling test is performed for assessment of the
      absorption of orally ingested radiolabeled crystalline cyano-Cbl; results should
      be interpreted cautiously. RESULTS: Vitamin B12 therapy should be lifelong. It is
      customarily administered intramuscularly. Other routes of administration have
      been studied. CONCLUSION: PA is one of the most treatable hematologic disorders.

PMID- 8309267
TI  - Pigmented conjunctival and scleral lesions.
AB  - OBJECTIVE: The multiple causes of pigmentations of the conjunctiva and sclera are
      reviewed, and the recommended therapeutic modalities are discussed. DESIGN:
      Information from personal experience and the recent literature is summarized to
      determine the optimal diagnostic and treatment approaches for suspicious
      pigmented conjunctival and scleral lesions. MATERIAL AND METHODS: Clinical
      descriptions and illustrations are presented to characterize these ocular
      lesions. RESULTS: Pigmented lesions of the conjunctiva and sclera arise from
      either melanocytes or nonmelanocytes and have a diverse differential diagnosis.
      These lesions can be classified into congenital melanosis, conjunctival nevi,
      acquired melanosis (secondary or primary), and conjunctival melanomas. In
      secondary acquired melanosis, the increased conjunctival pigmentation is caused
      by irradiation, hormonal changes, chemical irritation, or chronic inflammatory
      conjunctival disorders. The biologic behavior of primary acquired melanosis of
      the conjunctiva is a controversial topic with important implications because it
      may progress to melanoma. In patients with primary acquired melanosis, a biopsy
      is recommended in order to grade the disease, offer a prognosis, and direct
      further treatment. Conjunctival melanomas may arise from primary acquired
      melanosis, from nevi, or de novo, or they may be metastatic lesions. CONCLUSION:
      Of the wide spectrum of melanocytic conjunctival lesions, those with malignant
      potential are melanosis oculi, nevus of Ota, junctional nevus, compound nevus,
      primary acquired melanosis, and melanomas.

PMID- 8309268
TI  - Restrictive cardiomyopathy associated with the eosinophilia-myalgia syndrome.
AB  - OBJECTIVE: We report the first case of restrictive cardiomyopathy occurring in a
      patient with the eosinophilia-myalgia syndrome. DESIGN: In this article, we
      discuss the various clinical manifestations of the eosinophilia-myalgia syndrome.
      MATERIAL AND METHODS: In a 46-year-old woman with the eosinophilia-myalgia
      syndrome, orthopnea, chronic persistent edema, and severe dyspnea on exertion
      developed 2 years after she had discontinued use of L-tryptophan. Doppler
      echocardiography showed ventricular filling confined to early diastole and no
      atrial filling during ventricular systole--the Doppler hallmarks of restrictive
      disease. Right-sided cardiac catheterization revealed that the pulmonary wedge
      pressure equaled the pulmonary artery diastolic pressure and the mean right
      atrial pressure. A myocardial biopsy specimen showed dense endocardial fibrosis.
      Special immunofluorescent stains for eosinophilic granule major basic protein
      showed substantial deposition along the endocardial myocardial interface, an
      indication that eosinophils were present some time in the past. RESULTS: A follow
      up telephone call 14 months after the patient's initial assessment at the Mayo
      Clinic revealed that she had class III symptoms of congestive heart failure. She
      was receiving high doses of three diuretics daily, and her condition had improved
      considerably since her first examination at our institution. CONCLUSION:
      Restrictive cardiomyopathy may occur in the setting of the eosinophilia-myalgia
      syndrome and should be considered in patients with this disease in whom
      exertional dyspnea and peripheral edema occur.

PMID- 8309270
TI  - The biochemical basis of cobalamin deficiency.
AB  - OBJECTIVE: In this report, our goal was to summarize the current knowledge of the
      biochemical basis for the impaired DNA synthesis and neuropathy associated with
      vitamin B12 deficiency. MATERIAL AND METHODS: We reviewed the pertinent
      literature and our clinical experience with cobalamin deficiency. RESULTS:
      Studies have established that the megaloblastic hematopoiesis associated with
      vitamin B12 and folate deficiency is secondary to impaired DNA synthesis. Two
      mechanisms of impairment of DNA synthesis have been proposed: the "methylfolate
      trap hypothesis" and the "formate starvation hypothesis." One possibility is that
      both hypotheses may be contributory--that is, incoming dietary folate may be
      inaccessible for polyglutamation in accordance with the methylfolate trap
      hypothesis, whereas the formate starvation hypothesis may explain the failure to
      use already polyglutamated forms of folate. CONCLUSION: Although the
      pathophysiologic mechanisms of vitamin B12 and folate deficiency are not
      completely understood, nutritional anemias offer suitable models for the study of
      the biochemical basis of disease.

PMID- 8309269
TI  - Idiopathic intracranial hypertension.
AB  - OBJECTIVE: This review was undertaken to summarize the significant progress that
      has been made in the epidemiology of idiopathic intracranial hypertension (IIH),
      the changing nosology, and the diagnostic criteria and therapeutic strategy.
      DESIGN: We reviewed the pertinent literature on IIH published in major English
      language journals for the last 20 years. MATERIAL AND METHODS: The diagnosis,
      epidemiology, pathophysiology, complications, and treatment of IIH are described.
      RESULTS: IIH occurs at an average annual incidence rate per 100,000 persons of 1
      to 2 for the total population and 19 to 21 in obese females of the reproductive
      age-group. IIH is a recognized cause of reversible vision loss in adult obese
      women. The diagnosis of IIH requires a documented elevation of intracranial
      pressure, normal cerebrospinal fluid (CSF) composition, and normal findings on
      neuroimaging studies. At least two primary mechanisms for the development of
      increased CSF pressure in IIH have been postulated and supported by experimental
      data: vasogenic extracellular brain edema and a low conductance of CSF outflow at
      the arachnoid villi. This condition may be secondarily exacerbated by compression
      of intracranial venous sinuses by the increased intracranial pressure, resulting
      in a further reduction of flow across the arachnoid villi. The therapeutic
      strategy is determined by visual status, which needs close monitoring.
      CONCLUSION: Although medical measures to lower the intracranial hypertension are
      successful in the majority of patients, surgical therapy should not be delayed in
      those with significant or progressive vision loss. Based on recent advances, a
      practical approach has been described for the diagnosis, early detection of
      visual impairment, and targeting therapy to preserve the vision or to reverse
      recent loss of vision in patients with IIH.

PMID- 8309271
TI  - Posttraumatic cervical dystonia manifesting as isolated spasm of the middle
      scalene muscle.

PMID- 8309272
TI  - Monitoring of serum haloperidol.

PMID- 8309273
TI  - Autoimmunity and idiopathic dilated cardiomyopathy.

PMID- 8309274
TI  - Age-dependent modification of lipid composition and lipid structural order
      parameter of rat peritoneal macrophage membranes.
AB  - The effect of aging on the lipid composition and fluidity of rat peritoneal
      macrophage membranes has been determined using young (3 months), mature (12
      months) and aged (24 months) Wistar rats. In the aged animals, total phospholipid
      decreased significantly (P < 0.05), whereas cholesterol increased (P < 0.01),
      with an age-dependent increase in the molar ratio of cholesterol/phospholipid.
      The most marked change in phospholipid content was the significant (P < 0.001)
      age-dependent increase of phosphatidylserine and cardiolipin and the significant
      decrease of phosphatidylcholine and phosphatidylinositol. During aging there was
      a considerable decrease in arachidonic acid and docosapentanoic acid (about 50%
      in both cases). In contrast, an increase in the levels of oleic, linoleic and
      docosahexanoic acid was observed. Steady-state fluorescence polarization using
      1,6-diphenyl-1,3,5-hexatriene as the probe was used to estimate the lipid
      structural order parameter of macrophage membranes. There was a highly
      significant (P < 0.001) age-dependent increase in the lipid structural order
      parameter, which correlated well with the increased molar ratio of
      cholesterol/phospholipid in the membranes isolated from aged animals. The data
      suggests alteration in membrane lipid-protein interactions in aging, and are
      consistent with the hypothesis of the aging process.

PMID- 8309275
TI  - Sex-related and age-related differences in platelet function in vitro: influence
      of hematocrit.
AB  - Even minor changes in the sodium citrate concentration of citrated plasma from
      young probands due to diverse hematocrit values were found to affect platelet
      functional activity following in vitro stimulation. There were no differences
      between men and women in the platelet aggregation and TXB2 production of young
      probands with similar hematocrit values. Platelets from elderly persons virtually
      failed to respond to such changes in plasma sodium citrate. Mechanisms of
      increased platelet activity in the elderly are discussed. It is assumed that the
      age-related differences are caused by a more pronounced platelet response even to
      lower plasma calcium levels in citrated plasma.

PMID- 8309276
TI  - Calcium-dependent efflux of K+ ions from stimulated T lymphocytes of young and
      old mice.
AB  - The changes in the rate of efflux of potassium cations from ionomycin-, A23187-,
      and Concanavalin A (Con A)-stimulated lymphocytes from young and old mice were
      studied with an ion-selective electrode in a 'half-micro' system. It was found
      that, for both types of stimuli, the maximal rate of Ca(2+)-dependent efflux of
      K+ from young T cells was more than twice that attained by old cells. A
      bimodality of the curve illustrating change of efflux rate was observed,
      indicating possible existence of two types of Ca(2+)-dependent conductances. The
      kinetics of change of the efflux rate was similar for young and old cells
      stimulated with calcium ionophores, but differed in the cells stimulated with Con
      A. There, a lag period between mitogen addition and onset of measurable K+ efflux
      was absent in the case of old T cells, suggesting that function of other (Ca
      independent?) mechanisms of K+ efflux during the mitogen stimulation may also be
      changed there. The measured efflux of K+ was only partially dependent on the
      extracellular Ca2+. Also, it was quantitatively different in a 'physiological'
      medium containing 140 mM Na+, as compared to a sodium-free medium. Different
      blockers of potassium, calcium and sodium channels had at least partially
      inhibitory effect on the measured flux. Presented findings indicate that
      potassium conductance through Ca(2+)-gated K+ channels is impaired in T cells of
      old mice. Ca(2+)-dependent efflux of K+ in murine T cells is apparently conducted
      by a specific class of membrane channels, possibly consisting of two types of
      channels with different activation kinetics and pharmacological sensitivities
      (expressed in different subpopulations of T cells?). Impaired potassium
      conductance in old T cells is discussed as one of possible causes of age-related
      dysfunction of the immune system.

PMID- 8309277
TI  - Expression of alpha-glycerophosphate dehydrogenase during the development and
      aging of malaria vector Anopheles stephensi (Diptera: Culicidae).
AB  - alpha-Glycerophosphate dehydrogenase (GPDH) expression during the complete
      development and aging of Anopheles stephensi has been studied by electrophoretic
      and spectrophotometric techniques. Single gene locus seems to govern the
      developmental expression of three isozymes numbered from GPDH-1 to GPDH-3 in
      order of decreasing mobility. GPDH-3 was present in all the stages of
      development. GPDH-1 disappeared during senescence. GPDH-2, the band of
      intermediate mobility, was adult specific. GPDH-1 has been indicated to be more
      suitable for energy metabolism and GPDH-3 for lipid biosynthesis. Three
      codominant alleles control the four electrophoretic variants revealed in the
      laboratory strain. Quantitatively, the activity of GPDH continuously increased
      during development and showed its peak on day-4 adults of both sexes. However,
      the activity decreased during senescence. Tissue and sex specific differences in
      isozymes pattern have also been analysed. Changes in isozymes and specific
      activity have been correlated with the various physiological and morphological
      events occurring during development.

PMID- 8309278
TI  - Effect of age on antibody responses in low responder C57BL/10ScSn and high
      responder A/J strains of mice.
AB  - The IgM antibody response to sheep red blood cells (SRBC) appeared significantly
      earlier in A/J strain mice (already in 10-day-old animals), but after 21 days
      responses were higher in B10 mice. These differences disappeared after reaching
      adulthood and IgM responses after either primary or secondary immunization were
      thereafter comparable in these strains. High-responder A/J mice made
      significantly more IgG antibodies than low-responder B10 mice from 21 days of age
      and strong differences lasted until the age of 19 months, when IgG antibody
      production was again similar. Potentiation of IgM formation by simultaneous
      application of 10 micrograms of LPS was higher in B10 mice until 19 months of
      age. On the other hand, potentiation of the IgG response was markedly high in B10
      mice only in adult animals (3 months). Thereafter the potentiation was higher in
      A/J mice. The onset of Ig secretion in A/J mice was at 15 days and markedly
      increased at the age of 30 days. Levels of immunoglobulin synthesis remained
      extremely low in B10 mice. Age-related changes in IgG antibody production
      generally correlated with the decline of MHC class II antigen expression on
      peritoneal macrophages in these strains.

PMID- 8309279
TI  - Age-dependent alterations of human recombinant GM-CSF effects on human
      granulocytes.
AB  - The granulocyte-macrophage colony stimulating factor (GM-CSF) is an important in
      vivo regulator of granulopoiesis and neutrophil functions. It is well-known that
      the immune response and the transmembrane signalling in immune cells change with
      aging. We wished to elucidate the effects of GM-CSF in itself and in priming the
      activities of other inflammatory agents on neutrophils of elderly persons.
      Neutrophils of 20 healthy elderly (aged 60-90 years) and 20 healthy young (aged
      20-25 years) subjects were studied for superoxide anion production, intracellular
      free calcium mobilization, antibody dependent cellular cytotoxicity (ADCC) and
      intracellular killing activities. It was found that GM-CSF is unable to prime
      neutrophils of elderly subjects to the action of FMLP, metenkephalin or opsonized
      zymosan. By the use of Pertussis toxin and H7 it was demonstrated that a
      different signal transduction pathway in neutrophils of elderly subjects is
      activated by GM-CSF or FMLP if compared to that of young subjects. These results
      suggest that the lack of priming could contribute to the greater susceptibility
      of the elderly to infections and that the change of the signal transduction
      mechanism in neutrophils of elderly subjects might partly explain this
      phenomenon.

PMID- 8309280
TI  - Evaluation by dual-energy X-ray absorptiometry of age-related changes in body
      composition of male rats.
AB  - The purpose of this study was to determine the feasibility of using a recently
      developed procedure, dual-energy x-ray absorptiometry, to determine body
      composition in rats as a function of aging. Results were obtained that were
      consistent with previous findings for male rats.

PMID- 8309281
TI  - Age-associated changes in superoxide dismutase activity, thiobarbituric acid
      reactivity and reduced glutathione level in the brain and liver in senescence
      accelerated mice (SAM): a comparison with ddY mice.
AB  - The antioxidant defense alteration in young and old senescence accelerated mice
      (SAM) was studied by examining superoxide dismutase (SOD) activity,
      thiobarbituric acid (TBA) reactivity, and reduced glutathione (GSH) level in
      brain and liver tissues. The changes were compared with those in age-paired ddY
      mice, a strain exhibiting normal aging. SAM mice showed an age-dependent increase
      in SOD activity in liver, and an age-dependent increase in TBA reactivity in both
      the brain and the liver; they also showed an age-dependent decrease in the GSH
      level in the brain and the liver. When compared with ddY mice, SAM mice showed a
      higher SOD activity in the brain (at both 3 and 11 months old), a lower GSH level
      in the liver (at 3 months old), and a higher TBA reactivity in the liver (at 3
      months old). These findings suggest that the mechanism of senescence acceleration
      in SAM mice is to some extent related to free radical damage.

PMID- 8309282
TI  - Age-related alterations in the activation and expression of phosphotyrosine
      kinases and protein kinase C (PKC) among human B cells.
AB  - Age-related changes in the functional properties of human B cells have been
      reported by several groups, but little is known about the early biochemical
      events and signaling pathways that might be altered during aging. The present
      investigation examined whether differences in the activation of protein tyrosine
      kinases (PTK) and in the expression of protein kinase C (PKC) enzymatic activity
      could be identified in B cells from 16 elderly subjects (mean 77 years) compared
      to B cells from 15 young subjects (mean 33 years). B cells from young subjects
      stimulated with the surface immunoglobulin (sIg) crosslinkers anti-IgM or
      Staphylococcus aureus Cowan I (SAC) demonstrated rapid increases in PTK mediated
      de novo tyrosine phosphorylation of endogenous proteins. In comparison,
      stimulated B cells from elderly subjects were reduced 22-46% in tyrosine
      phosphorylations. Quantitation of the enzymatic levels and
      activation/translocation of PKC activity among resting and sIg stimulated B cells
      showed that B cells from approximately 50% of elderly subjects had significant
      reductions compared to B cells from young subjects. Further analyses of the
      expression of PTK and PKC enzymatic activity by stimulated B cells from elderly
      subjects demonstrated that aging was associated with greater heterogeneity in PKC
      expression and that defects in PKC enzymatic activity could coexist with
      relatively normal PTK activity. Thus, these data suggest that aging can alter the
      expression of PTK/PKC enzymatic activity in human B cells and that these age
      related alterations might perturb the balance between PKC-dependent and 
      independent signaling pathways.

PMID- 8309283
TI  - Influence of the energetic pattern of mitochondria in cell ageing.
AB  - Injections of mitochondria isolated from liver of young or old rats have been
      performed in young or old WI-38 human fibroblasts and the survival of the
      injected cells was followed with time. Cells having received young mitochondria
      behave as the control non-injected cells while cells having received old
      mitochondria showed signs of degeneration after a few days. Such a behaviour
      could however be obtained with young mitochondria when partially uncoupled. The
      negative effect of the presence of uncoupled mitochondria could be overcome by
      addition of a ketone body: D(-) beta-hydroxybutyrate. When comparisons were
      performed between injected young and old fibroblasts, old cells were found less
      efficient in counteracting the presence of uncoupled mitochondria. These results
      clearly indicate that old cells contain partly altered mitochondria which are
      less able to fulfil their energy requirement so that a general lowering of
      homeostasis but also an increased susceptibility, toward unfavorable situations
      is obtained.

PMID- 8309284
TI  - Augmentation of endothelin-1, prostacyclin and thromboxane A2 secretion
      associated with in vitro ageing in cultured human umbilical vein endothelial
      cells.
AB  - Differences in the secretion of the vascular regulators endothelin-1 (ET-1,
      prostacyclin (PGI2) and thromboxane A2 (TXA2) associated with ageing were
      investigated in cultured endothelial cells isolated from normal human umbilical
      veins (HUVECS). HUVECS at different population doubling levels (PDLs) were
      cultured in medium MCDB-104 supplemented with FBS and ECGF. Cell saturation
      density was determined by a Coulter counter, and concentrations of ET-1, PGI2 and
      TXA2 in the media were determined by radioimmunoassay. The cellular and nuclear
      size of HUVECS increased with advancing age, and the dividing ability decreased.
      Cell saturation density of HUVECS decreased 5-fold between PDLs 7 and 67 (P <
      0.01). The secretion of ET-1 by HUVECS at a young stage of growth (PDL 7.6)
      increased linearly between 0 and 36 h of incubation (P < 0.01). ET-1 secretion
      increased approximately 3-fold between PDLs and 67 (P < 0.01). PGI2 secretion
      increased 6-fold between PDLs 7 and 67 (P < 0.01), and TXA2 secretion increased
      18-fold between PDLs 7 and 67 (P < 0.01). The ratio of PGI2 to TXA2 secretion
      decreased 3-fold between PDLs 7 and 40 (P < 0.01), and remained at the lower
      ratio between PDLs 40 and 67. This data indicates that the anti-thrombotic or
      anti-vasoconstrictive role of endothelial cells may decrease during in vitro
      ageing.

PMID- 8309285
TI  - The effect of caloric restriction on the lateral diffusion constant of hepatocyte
      membrane proteins in C57BL/6 male mice of different ages: FRAP studies on liver
      smears.
AB  - The lateral mobility of proteins in hepatocyte plasma membranes was compared in
      calorically restricted and ad libitum (AL)-fed C57BL/6 male mice in age groups
      from 7 to 28 months. Caloric restriction was achieved by means of the every-other
      day (EOD) feeding regimen, maintained for various periods from 1 to 15 months.
      Protein lateral diffusion constant (D) in hepatocyte membranes was measured by
      means of fluorescence recovery after photobleaching (FRAP) in liver smears. The
      peroxide-induced autofluorescence (PIAF) was utilized as a fluorescent label. A
      mild (1 mM for 10 min) H2O2 treatment of liver smears produces oxidation of
      riboflavin that is bound to all proteins of the cell membrane. Using this
      technique, the average lateral diffusion constant (D) and the fractional recovery
      (FR) of these proteins can be measured. EOD feeding resulted in a significant
      decrease in body weights and also a significant increase in the values of D in
      all age groups after 1 month of EOD feeding. After 3.5 months of EOD feeding a
      further increase of D was observed (up to about 15%). Nevertheless no further
      change in D occurred if the EOD feeding was maintained for 6.5 or even 15 months.
      The negative linear age correlation of D observed in the AL-fed animals was
      present also under the EOD feeding; however, the whole regression equation
      shifted towards higher values. These experiments indicate that caloric
      restriction influences the lateral diffusion constant of membrane proteins in
      hepatocytes. The results are interpreted as a result of an increased protein
      turnover caused by the caloric restriction.

PMID- 8309286
TI  - Increase in housing temperature can alleviate decrease in white blood cell counts
      after energy restriction in C57BL/6 female mice.
AB  - White blood cell (WBC) counts decrease after energy restriction (ER) in both
      rodents and humans. ER reduces cellular proliferation rates in various organs of
      rodents. Increases in housing temperatures can cancel this inhibitory effect of
      ER. We investigated whether a high housing temperature can alleviate decreases in
      WBC counts after ER, since peripheral WBC counts at basal levels are considered
      to represent cellular proliferation rates in the bone marrow. C57BL/6 female mice
      were allocated to three groups: the control (397 kJ/week), the ER (176 kJ/week)
      and the ER housed-in-incubator group (ERI: 134 kJ/week). The former two groups
      were housed at 21-23 degrees C and the third group was housed at 30 degrees C. At
      4 and 13 months of age, WBC counts were significantly lower in ER or ERI mice
      than in control mice. WBC counts, however, were significantly higher in ERI mice
      (194%) than in ER mice at 13 months of age. A high housing temperature was proved
      to antagonize the effect of ER on WBC counts, as it antagonizes suppressive
      effects of ER on cellular proliferation rates in various organs.

PMID- 8309287
TI  - [Susceptibility of methicillin-sensitive and methicillin-resistant staphylococci
      to ciprofloxacin].
AB  - Investigations were carried on 352 strains of Staphylococcus aureus and 105
      strains of coagulase-negative staphylococci, isolated from various clinical
      materials and derived from some regions of the country. Methicillin-resistance
      was tested by an antibiotic dilution method in solid Mueller-Hinton medium with
      addition of 2% NaCl. Staphylococci with MIC higher than 4 micrograms/ml were
      considered as resistant. The same method for testing resistance to ciprofloxacin
      was used. Only one strain (S. aureus) was resistant to both ciprofloxacin and
      methicillin. All remaining strains of staphylococci were ciprofloxacin
      susceptible. The MIC for all of them was not higher than 2 micrograms/ml,
      regardless of resistance to methicillin. Some slight differences in MIC50 and
      MIC90 values were found between MRSA and MSSA and they were, respectively, 1
      microgram/ml and 0.25 microgram/ml, and 2 micrograms/ml and 1 microgram/ml. Mean
      MIC of ciprofloxacin for MRSA was 1.1 microgram/ml and for MSSA it amounted to
      0.4 microgram/ml. Range of MIC was following: MRSA--0.12 microgram/ml--16
      micrograms/ml and MSSA--0.12-2 micrograms/ml. Coagulase-negative staphylococci,
      both methicillin-resistant and methicillin-sensitive, exhibited same value for
      MIC50, MIC90 and MIC range and they were following: 0.5 microgram/ml, 1
      microgram/ml and 0.12-1 micrograms/ml. Both groups differed slightly in mean MIC
      values which was 0.6 microgram/ml for methicillin-resistant strains and 0.47
      microgram/ml for methicillin-sensitive staphylococci. It seems that within
      staphylococci isolated in Poland there is no correlation between resistance to
      methicillin and ciprofloxacin, which is frequently pointed out by other authors.

PMID- 8309288
TI  - [Action in vitro of disodium ethylenediaminetetraacetic acid (Na2EDTA) and
      antibiotics on resistant strains of staphylococcus aureus].
AB  - The investigation of action of Na2EDTA and doxycycline on strains of
      staphylococci resistant to doxycycline was performed by two methods: serial
      dilutions of tested substances in the fluid and solid medium. MIC values for
      Na2EDTA, doxycycline and both substances together were determined. Both methods
      resulted in an observation that for majority of tested doxycycline-resistant
      strains, application of various concentrations of doxycycline together with
      Na2EDTA resulted in a change of sensitivity of bacteria to the antibiotic by
      lowering concentration needed for bacterial growth inhibition. It seems that in
      further studies laborious and time-consuming method of serial dilutions in the
      fluid medium, should be replaced by more convenient and easier to perform method
      of serial dilutions of drugs in solid agar medium.

PMID- 8309289
TI  - [Treatment with neomycin and Na2EDTA for skin infections in rabbits caused by
      Staphylococcus aureus].
AB  - The rabbits were infected intradermally with a strain of S. aureus resistant to
      neomycin. They were treated with neomycin, Na2EDTA and by combination of these
      substances, which were applied as a cream with differing concentrations of these
      factors. Simultaneous application of neomycin and Na2EDTA for treatment of
      experimental staphylococcal infections caused in rabbits with a strain resistant
      to neomycin, resulted in acceleration of healing of pustular changes, when
      compared with results obtained in animals treated with these substances alone.

PMID- 8309290
TI  - [Group B streptococci as an etiologic agent of infections in adults and their
      characteristics].
AB  - The investigation was performed on 1471 bacteriologically-positive samples of
      materials derived from patients hospitalized in various hospital wards (mainly
      gynecology and obstetrics). Group B streptococci were in 10% etiological factors
      of infections in patients from gynecological and obstetrical wards. These
      bacteria were isolated in 25% from pus, 15.7% from vaginal smears and in 13.7%
      from cervix uteri. In urinary tract infections, group B streptococci were present
      in 10.7% of urine samples with positive bacteriological result. They were also
      isolated from 8.3% of sperm samples treated because of infertility. Isolated
      strains of group B streptococci belonged most frequently to following serotypes:
      Ic, III, R, Ib and II consisting respectively 33.5, 19.3, 12.9, and 11.0% of all
      strains out of 155 tested serologically. These results demonstrate that group B
      streptococci are frequently causative in bacterial infections of hospitalized
      patients.

PMID- 8309291
TI  - [Usefulness of plasmids as epidemiologic markers for typing of Klebsiella].
AB  - The study was aimed at evaluation of utility of plasmids as epidemiological
      markers for interspecific differentiation of 200 strains of Klebsiella isolated
      from patients with generalized infections and hospitalized at intensive care ward
      of the Gdansk Medical Academy. Strains isolated from the ward environment were
      also investigated. In the first phase of this study classical methods of typing
      were used, such as determination of the biochemical, bacteriocin (susceptibility
      to 8 bacteriocins) and phage types, and MIC for 9 antibiotics. Basing on these
      methods it was found that 41 types of Klebsiella pneumoniae, 13 types of
      Klebsiella oxytoca and 1 type of Klebsiella ozenae occur. Six groups of bacteria
      were differentiated in the group which had the same type. These strains were
      investigated for plasmid and restrictive patterns. Identity of types occurring in
      individual groups was detected. For one of them, a restrictive pattern was
      determined by cleavage of plasmid DNA by a restrictive Eco RV enzyme. In
      remaining groups such pattern was not found, both after treatment with Eco RV and
      Hha I enzyme and this may be associated with modification of the plasmid DNA.
      Strains belonging to one of these groups did not contain plasmids in their cells.

PMID- 8309292
TI  - [Analysis of susceptibility of bacteria isolated from clinical material to
      cefuroxime, ceftazidime and cefotaxime].
AB  - The authors have compared the susceptibility of bacterial strains isolated from
      clinical material in 1990 and 1991 to the most frequently used cephalosporins:
      cefuroxime, ceftazidime and cefotaxime. The highest susceptibility in 1990 was to
      cefotaxime, which was seldom used at that time, unlike cefuroxime and
      ceftazidime. In 1991 an increase in the number of strains resistant to cefotaxime
      was found, in parallel with a further rise in resistance to cefuroxime and
      ceftazidime. Frequent use of an antibiotic in a certain region favours the
      development of resistance. This observation calls for rational therapy with
      antibiotics, supported by regular studies of susceptibility of the strains in the
      region.

PMID- 8309293
TI  - [Susceptibility of bacteria to selected cephalosporins of the II and III
      generation].
AB  - Susceptibility of 1893 strains of bacteria responsible for infections in children
      treated in the Institute of Mother and Child in 1991 was investigated.
      Sensitivity to cefuroxime, cefamandole, cefotaxime, ceftriaxone and ceftazidime
      were tested by application of discs produced by Bio-Merieux. MIC for cefuroxime
      against selected clinical strains was determined by a solid medium dilution
      method. Cefamandole in comparison with cefuroxime was more effective for S.
      aureus (94.7%), coagulase-negative staphylococci (93.1%), P. rettger (87.5%), M.
      morganii (76.9%) and P. vulgaris (63.6%). Cefuroxime was more active against P.
      mirabilis and C. freundii. Percentages of Enterobacteriaceae and Gram-positive
      cocci sensitive to III generation cephalosporins were high and amounted to 60
      100%. Cefotaxime was active against higher percentages of S. marcescens (94.1%),
      C. freundii (76.0%), K. pneumoniae (54.8%), S. aureus (79.0%) and coagulase
      negative staphylococci (82.2%) when compared with ceftazidime and ceftriaxone. P.
      aeruginosa, other non-fermenting Gram-negative bacteria and A. calcoaceticus were
      most susceptible to ceftazidime. Comparison of MIC50 and MIC ranges for
      cefotaxime and cefuroxime indicates significantly higher activity of cefotaxime
      toward all tested strains of Enterobacteriaceae.

PMID- 8309294
TI  - [Studies of the effect of cephradine and lincomycin on dynamics of selected
      parameters of nonspecific cellular immunity in experimental animals].
AB  - Rabbits of group I received cephradine i.m. and of group II lincomycin in mean
      therapeutic doses (calculated by body weight) for seven days. Determinations were
      performed before application of antibiotics and at 7, 14, 28 and 42 days of the
      study. Following tests were performed: phagocytosis index by determination of
      phagocytizing neutrophils, phagocytosis index and the NBT test. After application
      of cephradine, each determination revealed significant decrease of percentage of
      phagocytosing neutrophils, whereas phagocyte index was lowered at 14 day and the
      NBT value in 14 and 28 days of investigation. After application of lincomycin,
      value of percentage of phagocytosing neutrophils was lowered at the 14 day, and
      of phagocytosis index at the 7 day. NBT test values were lowered at 7 and 28 day
      and increased at the 42 day of the study.

PMID- 8309295
TI  - [Studies on the effect of cephradine, cefuroxime, lincomycin and amikacin on
      complement levels in experimental animals].
AB  - Rabbits were injected intramuscularily with antibiotics in mean therapeutic doses
      (calculated by body weight) for the period of 7 days. Group I received
      cephradine, group II--cefuroxime, group III--lincomycin and group IV--amikacin.
      Determination of complement level by CH50 method was performed before application
      of antibiotics and at 7, 14, 28 and 42 day of the study. Application of the
      cephalosporin antibiotics did not result in any changes in the complement level.
      After application of lincomycin, complement level increased at the 17 day and
      after amikacin treatment it was higher after 7 days of investigation.

PMID- 8309296
TI  - [Characteristics of lactobacillus species strains isolated from reproductive
      organs in various clinical cases].
AB  - The study was aimed at detection of presence of Lactobacillus species bacteria in
      167 samples of material derived from vagina of patients with cervix uteri (22
      samples), chronic vaginosis (100 samples) and from women after treatment of
      inflammatory diseases (45 samples). Out of 100 isolated strains of Lactobacillus
      only 13 belonged to L. acidophilus. They were mainly present (10 strains) in
      patients after effective treatment of inflammatory diseases of reproductive
      organs. Remaining strains belonged to L. jensenii (18 strains) and Lactobacillus
      sp. (69 strains) and did not cleave glycogen. This was detected by quantitative
      determinations of lactic acid in cultures of these bacteria in the fluid media
      containing 0.25% of glycogen. It seems that treatment of bacterial infections of
      reproductive organs should be concentrated on not only elimination of pathogenic
      bacteria, but also on noneffective strains from Lactobacillus species (strains
      unable to cleave glycogen with production of lactic acid).

PMID- 8309297
TI  - [Gardnerella vaginalis in infections of reproductive organs].
AB  - The study was aimed at multidirectional studies on bacteria isolated from smears
      from vagina and cervix uteri in 226 patients with inflammatory states of their
      reproductive organs. Most frequently isolated aerobic bacteria were Gram-negative
      -27%, mainly E. coli, and Enterococcus faecalis--in 18% of cases. Anaerobic
      bacteria were isolated in 81% of cases: Gardnerella vaginalis was isolated in 28%
      and Lactobacillus in 53% of cases. Other anaerobic bacteria were: Peptococcus
      asaccharolyticus (15.5%), Streptococcus sp. (15.9%), and Bacteroides
      melaninogenicus (14.1%). Gardnerella vaginalis was most frequently found in
      chronic cases of vaginosis (41.7%). All strains of G. vaginalis were susceptible
      to cefotaxime, while 15-40% of them were resistant to gentamycin, tetracycline
      and metronidazole.

PMID- 8309298
TI  - [Occurrence of Helicobacter pylori in mucous membrane of stomach in patients with
      duodenal ulcer and inflammation of stomach mucous membrane].
AB  - In 1990-1991 microbiological studies were performed aimed at determination of
      frequency of occurrence of Helicobacter pylori in patients treated because of
      peptic ulcer in Department of Gastroenterology in Katowice. Studies were
      performed in 112 patients. Out of these, in 73 duodenal ulcer was detected
      endoscopically (group I), in 26--inflammation of stomach mucous membrane with
      erosion (group II), and in 13--both duodenal ulcer and erosion of stomach
      membrane (group III). Samples from mucous membrane of pylorus and of stomach
      taken endoscopically were tested microscopically and in culture. Helicobacter
      pylori was found in 74 patients (66.1%). Frequency of isolation was different in
      individual groups. Helicobacter pylori was found in 51 patients (70%) of group I,
      15 (58%) of group II and in 8 (61%) of group III. Helicobacter pylori was most
      frequently isolated from patients with duodenal and stomach ulcer (81.3%).

PMID- 8309299
TI  - [Effect of bismuth salts in elimination of Helicobacter pylori from gastric
      mucosa in patients with duodenal ulcer].
AB  - Bismuth salts belong do basic drugs used for elimination of Helicobacter pylori
      (HP), a microorganism which is postulated to participate in etiopathogenesis of
      duodenal ulcer. The study was aimed at evaluation of effectiveness of application
      of tripotassium bismuth citrate (Ventrisol-Polfa) in elimination of HP and its
      influence on treatment of the ulcer. In 30 patients with diagnosed endoscopically
      duodenal ulcer, Ventrisol in tablets was applied (2 x 2); it was also used in its
      fluid form (4 x 5 ml). The time of treatment amounted to 28 days. During
      endoscopy, samples from various parts of the stomach were taken for
      microbiological inspection and they were studied in direct smear and in culture.
      HP was isolated from 20 out of 30 patients (37%) before treatment. After
      application of Ventrisol, the bacteria were present in 11/30 (34%) treated
      patients (p < 0.05). There was no influence of the form of drug for elimination
      of HP. No dependence was also found between elimination of HP and healing of the
      ulcer.

PMID- 8309300
TI  - [Occurrence of species of the Acinetobacter genus in material from patients and
      in the hospital environment].
AB  - 370 clinical strains of genus Acinetobacter were classified in accordance of
      taxonomy of this group of bacteria introduced by Nouvet and Grimont (1986). Most
      frequent species isolated was A. baumanii (195), followed by A. lwoffii (71), A.
      junii (79) and A. haemolyticus (27). A. calcoaceticus and A. jonsonii were
      present only sporadically. A. baumanii was isolated from bronchial secretions
      (36.9%), sputum (20.5%), blood (8.7%), pus (8.2%) and ur@ine (8.2%). A. lwoffi
      was isolated above all from throat smears (26.8%), sputum (16.9%), bronchial
      secretions (16.9%) and urine (16.9%). A. junii was present in sputum (25.7%),
      blood (17.6%), throat smears (17.6%), bronchial secretions (13.5%) and urine
      (12.2%).

PMID- 8309301
TI  - [Anaerobic Propionibacterium in opportunistic infections].
AB  - In three cases, two of which regarded exudative pericardium inflammation and one
      of lung abscess, biopsy revealed negative bacteriological results. Blood cultures
      resulted in culture of anaerobic Gram-negative bacteria from Propionibacterium
      genus. Precise chemo- geno-taxonomic studies were performed which confirmed
      generic identification of isolated strains. These were following: in cell wall--L
      DAP, alanine, glycine, galactose, glucose, mannose; lack if mycolic acids; %GC 58
      59. Basing on additional bacteriological studies it was established that two
      strains belong to the genus Propionibacterium acnes (type I), while third strain
      appeared to be Propionibacterium propionicum (before Arachnia propionica). These
      results confirm growing participation of relative pathogenic bacteria in
      opportunistic infections. It suggests necessity of blood cultures in cases
      subjected to prolonged therapy, especially when immunosuppression is involved.

PMID- 8309302
TI  - [Etiologic bacterial factors of infections in patients treated at the clinical
      anesthesiology ward and with intensive therapy].
AB  - Bacteriological investigations were carried on 264 patients treated in 1988-1990.
      1736 samples of biological materials were taken and it amounts to 6-7 samples
      from each patient. Most frequently isolated microorganisms were: Pseudomonas
      aeruginosa (15%), Proteus mirabilis (13%), Klebsiella pneumoniae (10%) and
      Staphylococcus aureus (10%). Serological typing of Pseudomonas aeruginosa was
      performed according to Habs and domination of immunotype P16 (30%) was detected.
      Majority of isolated Klebsiella pneumoniae were not typable with basic and
      broadened phage set. One strain was susceptible to phages KI12 and KI27. This
      phage type was not isolated in Poland before. Staphylococci were most frequently
      susceptible to group II phages (29%), additional phages (19%) and 15% were not
      typable with the phage set used. Isolated bacteria were in majority resistant to
      numerous antibiotics.

PMID- 8309303
TI  - [Quantitative changes of bacterial flora from the oral cavity and throat in
      children with acute lymphoblastic leukemia].
AB  - Quantitative investigations were carried on aerobic and anaerobic bacterial flora
      of oral cavity and throat in 44 children in the age of 5-10 years with acute
      lymphoblastic leukemia, intensively treated with cytostatics, and in 23 healthy
      children which served as a control group. Samples of saliva from leukemic
      children revealed significantly higher than in control group--presence of aerobic
      bacteria, particularly streptococci and enterococci. Material from throat was
      differing only in regard to staphylococci. Moreover, in children with leukemia,
      Gram-negative rods were present, which was not the case in the control group.

PMID- 8309304
TI  - [Bacteriologic examinations of patients with burns].
AB  - Bacteriological studies were performed on 189 patients treated during 1985-1989.
      800 samples were tested which were taken from various sites of burn wound (3-5
      smears from a patient). Surface of burn amounted to 15-86% and degree of burn was
      IIb/III. In 772 samples, 2073 bacterial strains were found. Most frequent were
      Pseudomonas aeruginosa (31%) and Staphylococcus aureus (29%). Remaining strains
      consisted chiefly of Proteus mirabilis, Pseudomonas cepacia, Klebsiella
      pneumoniae, Escherichia coli and Acinetobacter calcoaceticus. Serological typing
      of Pseudomonas aeruginosa carried according to Fisher demonstrated dominance of
      immunotype T3.7 (43%). Staphylococcal strains were most frequently sensitive to
      group III phages and/or supplementary phages.

PMID- 8309305
TI  - [Biochemical differentiation of proteus strains from various clinical materials].
AB  - The material consisted of 729 strain of Proteus isolated from clinical samples in
      three microbiological laboratories of city of Lodz region. Our of these strains,
      466 were Proteus mirabilis, and remaining represented: P. penneri-13 strains, P.
      vulgaris (II biogroup)-56 and 54 strains which were not classifiable on the basis
      of biochemical properties and scheme elaborated by Hickman et al. for biogroups
      of P. vulgaris. The authors indicate feasibility of differentiation of P.
      vulgaris basing on biochemical tests as a supplementary method to other tests of
      intracellular differentiation of Proteus.

PMID- 8309307
TI  - [Effect of Staphylococcal proteinase on adherence of Candida albicans to mucous
      membrane cells in vitro].
AB  - The study was aimed at evaluation of influence of staphylococcal proteinase on
      adherence of Candida albicans to the cheek mucous membrane cells. Epithelial
      cells were preincubated with the enzyme which was followed by adherence tests.
      Significant increase of number of cells of Candida albicans adhering to
      epithelial cells preincubated with enzyme in concentrations of 10 micrograms/ml
      and 50 micrograms/ml, was detected. Staphylococcal serine protease seems to play
      an important role in mixed infections caused by fungi and bacteria.

PMID- 8309306
TI  - [Properties of Pseudomonas aeruginosa strains. Adherence and proteolytic
      activity].
AB  - The material consisted of 141 strains of Pseudomonas aeruginosa isolated from
      various sources and derived from children treatment in the Institute of
      Pediatrics. Adherence properties of these strains were tested by application of
      an own micromethod with application of 96 well titration plates. Proteolytic
      activity was investigated by means of gel radial diffusion with application of
      caseine and elastin as substrates. It was established that reverse correlation of
      adherence and proteolytic activity exists.

PMID- 8309308
TI  - [Candida parapsilosis in reproductive organ infections].
AB  - Frequency of occurrence of strains of C. parapsilosis, their susceptibility to
      drugs and importance in pathogenesis of vaginal mycosis, was evaluated. Strains
      of C. parapsilosis were isolated in 44 cases which comprises 1.34% of a total
      number of 3275 tested Candida-like strains. Vaginal mycoses occurred in presence
      of Lactobacillus sp., normal pH values of vaginal contents, whereas leukocytosis
      was differing. Following drugs were used for testing susceptibility of C.
      parapsilosis: nystatin, pimaricin, amphotericin B, flucytosine, cotrimoxazole,
      miconazole, ketoconazole, tioconazole, fluconazole and itraconazole. It has been
      demonstrated that 38.3% strains of C. parapsilosis were exhibiting lowered
      activity toward amphotericin B, nystatin (23.5% resistant) and flucytosine (11.7%
      resistant). Tested strains were susceptible to remaining drugs within 94.1% and
      100%.

PMID- 8309309
TI  - [Evaluation of susceptibility of dermatophytes to antifungal drugs].
AB  - A serial dilution and a disc method were used for evaluation of susceptibility of
      50 dermatophyte strains belonging to the species Trichophyton rubrum,
      Trichophyton mentagrophytes, Microsporum canis and Epidermophyton floccosum.
      Following drugs were investigated: griseofulvin, pimaricin, clotrimoxazole,
      miconazole, ketoconazole, biphonazole and naftifin. Application of two methods of
      testing resulted in high convergence of determinations. Naftifin was most
      effective and pimaricin least active. Among imidazole drugs, relatively high
      activity against dermatophytes was exhibited by clotrimoxazole and ketoconazole.
      Strain of Trichophyton rubrum were more susceptible to antifungal drugs than
      strains of Trichophyton mentagrophytes.

PMID- 8309310
TI  - [Evaluation of mycologic and myco-serologic studies of materials derived from the
      respiratory tract of patients in the years 1986-1990].
AB  - The material for mycological studies consisted of 7146 samples of respiratory
      tract material derived from 7764 patients (6495 samples of sputum, 235 bronchial
      rinsings and 416 throat smears). Serological studies were performed with 684
      samples of serum by application of indirect immunofluorescence (IF) and gel
      immunodiffusion (ID) tests. Candida- like fungi in amounts which were
      diagnostically significant (10(6) cells/ml) were found in 16.7% samples of
      sputum. among fungi isolated from sputum there were 14 species of Candida- like
      fungi, mainly C. albicans (76%) and 7 species of moulds (including A. fumigatus
      0.7%). Fungi were isolated from bronchial washings in 23.4% of samples. Among the
      isolated strains, 12.6% of Candida albicans were resistant to 5-fluorocytosine
      and 14.1% were resistant to amphotericin B. Antibodies against C. albicans by
      application of both IF and ID were found in 2.2% samples of serum. Antibodies
      against A. fumigatus were present in 11.6% of samples.

PMID- 8309311
TI  - [Effect of treatment with autologous staphylococcal vaccine on the course of the
      immunologic process].
AB  - In 18 patients with furunculosis and in 9 with chronic inflammation of upper
      respiratory tract, some cellular immunity parameters were tested. These were:
      phagocytosis index and bactericidal activity against leukocytes. Humoral immunity
      was also investigated by measurement of serum gammaglobulins. All test were
      performed before treatment and 30 days after application of the last dose of
      autologous vaccine. In 12 patients with furunculosis, improvement of the clinical
      status (disappearance of furunculosis) was appearing together with an increase of
      phagocytosis index and bactericidal activity of leukocytes without changes in
      gamma-globulin levels. No such changes were found in remaining patients in whom
      no clinical improvement was found. The authors suggest that cellular immunity
      factors studied in this investigation permit for evaluation of the immunity
      status in patients receiving autologous staphylococcal vaccine.

PMID- 8309312
TI  - Rapamycin: a novel immunosuppressive macrolide.

PMID- 8309313
TI  - Interactive multivariate modeling of ArgGlyAsp (RGD) derivatives.

PMID- 8309314
TI  - Multivariate influence of polyinositols on IP3 in diaphragm: individually applied
      matrix and vectorial analysis of trauma from small and large body surface area
      burn groups.
AB  - In this report, we have used multivariate and vectorial analyses to aid in
      understanding perturbations in diaphragmatic signal transduction in consequence
      to burn trauma. This trauma results from shock emanating from skin scald burn.
      Its respiratory complications are well-known. Relational matrices derived from
      experimental animal groups of varying body surface area (% BSA) burn size were
      subjected to individual multiple linear regression and vectorial analyses. Such
      individual matrices tested the simultaneous dependency of inositol 1,4,5
      triphosphate (IP3) on inositol 1,4-biphosphate (I1,4P2), inositol 1-phosphate
      (I1P) and inositol. Understanding the contribution of multiple independent
      parameters simultaneously co-governing the dependency of IP3 offers new insight
      in regulating signal transduction mechanisms under the duress of burn trauma.

PMID- 8309315
TI  - Increase of histidine decarboxylase activity in mice hypothalamus after
      intracerebroventricular administration of lipopolysaccharide.
AB  - The effect of intracerebroventricular (icv) administration of lipopolysaccharide
      on histidine decarboxylase activity and histamine content in the hypothalamus
      were investigated in male mice of ddY strain in vivo. Two-fold increase in
      histidine decarboxylase activity (HDC) was observed 4 h after administration of
      50 mcg lipopolysaccharide, and HDC activity returned to the basal level within 12
      h after injection. Furthermore, histamine contents showed a slight decrease at 1
      and 2 h and a mild increase at 12 h after administration. However, changes in
      histamine content were not statistically significant. These results suggest that
      the increase of HDC activity in the hypothalamus by lipopolysaccharide may be
      involved in the central neuroimmune responses.

PMID- 8309316
TI  - Ocular effects of topical administration of the phosphodiesterase III inhibitor
      milrinone in rabbits and cats.
AB  - Increases in intracellular cAMP levels have previously been shown to decrease
      intraocular pressure (IOP) and increase ocular blood flow (OBF). However, the
      ocular effects of milrinone, which increases intracellular cAMP levels via
      selective cAMP PDE III inhibition, have not been investigated. The purpose of
      this study was to investigate the ocular effects of topically administered
      milrinone at different concentrations in rabbits and cats. When compared to
      vehicle in conscious rabbits, topical administration of milrinone at 0.03%
      decreased IOP (-14.1 +/- 2.6% vs. -7.4 +/- 3.7%, max. changes expressed as mean
      +/- SEM), at 0.1% increased IOP (10.4 +/- 8.5% vs. -1.7 +/- 4.1%), and at 0.01%
      and 1% did not significantly affect IOP. Neither pupil size nor central corneal
      thickness were affected by milrinone. Additionally, there were no signs of
      inflammation and no effects on corneal clarity. In anesthetized cats, topical
      administration of milrinone at 0.01-0.3% increased OBF (38.9 +/- 6.0% for
      milrinone vs. -7.4 +/- 4.4% for vehicle), and at 0.03%-0.3% decreased mean
      arterial pressure (-19.0 +/- 5.6 vs. 3.0 +/- 4.1 mmHg) in a dose-related manner.
      The durations of OBF enhancement (1.5-2.5 h) and MAP reduction (less than 30 min
      to 2 h) were also dose-dependent. In conclusion, milrinone induced biphasic IOP
      effects: IOP was decreased at 0.03% but increased at 0.1%. Milrinone at 0.01%
      increased OBF, possibly via a local vasodilator effect, and at 0.03-0.3%
      increased OBF, possibly via local and systemic effects. These data suggest that
      cAMP PDE III inhibitors such as milrinone may have efficacy as agents which
      enhance ocular blood flow following topical ocular application.

PMID- 8309317
TI  - SURVIVAL--an integrated software package for survival curve estimation and
      statistical comparison of survival rates of two groups of patients or
      experimental animals.
AB  - SURVIVAL, a new integrated software package for survival curve estimation and
      statistical comparison of survival rates of two censored or uncensored groups of
      patients or experimental animals, is described and demonstrated. The software is
      based on the calculation of the Kaplan-Meier estimates of survival curves and
      utilizes the Mantel-Haenszel and/or Fisher's test for the statistical comparison
      of the corresponding survival rates. SURVIVAL can be used for statistical
      evaluation of survival data obtained either on sequentially created or fixed size
      groups. The software is menu driven to provide a very user friendly tool for
      analyzing survival data. It may be of great value mainly in clinical use because
      it automatically enables evaluation of a large set of survival data, sequentially
      collected in SURVIVAL's own database during a long survival study, with entry and
      evaluation possible at any time during the study.

PMID- 8309318
TI  - A simple method for the determination of articaine and its metabolite articainic
      acid in dentistry: application to a comparison of articaine and lidocaine
      concentrations in alveolus blood.
AB  - This study was undertaken to develop a time- and cost-effective method for the
      detection of articaine and articainic acid in alveolus blood by high-performance
      liquid chromatography with a simple method of sample pretreatment. To overcome
      the problem of very rapid hydrolysis a method for controlling hydrolysis in vitro
      after blood sampling was developed. Blood samples were withdrawn from the
      alveolus of the upper molars 2-14 min after submucous injection of articaine (2.0
      ml 4%) or identical injection of lidocaine (2.0 ml 2%). The higher blood levels
      found for articaine correspond to the higher concentration of the drug in the
      injection solution. A relationship between the serum concentration of articaine
      and lidocaine, respectively, and the time between injection and blood sampling
      could be established.

PMID- 8309320
TI  - [Organ donation--when should inquiry be made?].

PMID- 8309319
TI  - The monophasic action potential technique and its application in cardiac
      electropharmacology.
AB  - Monophasic action potentials (MAPs) are a measure of electrical activity of local
      myocardial cells recorded from the epicardial or endocardial surfaces of the
      beating heart, in vivo, using a positive pressure-contact electrode or electrode
      catheter. The MAP technique is a reliable and safe method for studying and
      detecting the cardiac electrophysiological and electropharmacological activities
      and mechanisms in animal heart, and most importantly, in human hearts. In the
      present review we discuss the monophasic action potential technique and its
      applications to electropharmacology, especially antiarrhythmic and antiischemic
      agents.

PMID- 8309321
TI  - [Who will revise the Swedish health policy?].

PMID- 8309322
TI  - [Is follow-up of infectious diseases unprofitable?].

PMID- 8309323
TI  - [The intern is needed at the family practitioner's office!].

PMID- 8309324
TI  - [Individualizing needed in aminoglycoside therapy].

PMID- 8309325
TI  - [Gynecologic surgery is not only laparoscopic technique. Knowledge of routine
      gynecology is also needed].

PMID- 8309326
TI  - [Laparoscopic hysterectomy. Further knowledge of advantages and disadvantages is
      necessary].

PMID- 8309327
TI  - [Battered and sexually abused children. Handling routines are based on analysis
      of medical records].

PMID- 8309328
TI  - [Local recurrence after rectal cancer surgery. A surgical and oncological
      challenge].

PMID- 8309329
TI  - [Desmopressin as a hemostatic. Selective treatment is most effective].

PMID- 8309330
TI  - [Overconsumption of antibiotics. Indications and choice of preparation must be
      reevaluated].

PMID- 8309331
TI  - [Antinuclear antibodies. Diagnostic potential in systemic rheumatic diseases].

PMID- 8309332
TI  - [Supportive therapy. The ugly duckling of psychiatry].

PMID- 8309333
TI  - [Supportive therapy in practice. Technical rules of thumb for effective
      psychotherapy].

PMID- 8309334
TI  - [Fibromyalgia. Views on diagnosis and management].

PMID- 8309335
TI  - [Treatment of fibromyalgia. Positive experiences with group education].

PMID- 8309336
TI  - [Chemical analyses in primary health care. Important link in the rapid technical
      development].

PMID- 8309337
TI  - [How will they cope? Relatives are an important resource in home care].

PMID- 8309338
TI  - [Alcohol--when should the physician intervene? New data motivate prevention].

PMID- 8309339
TI  - [Fibronectin--a key substance in pathogenesis of liver cirrhosis?].
AB  - Diffuse and chronic liver damage leads to scar formation of the liver structure
      accompanied with a disproportionate increase of the extracellular matrix (ECM)
      constituents. Therapeutic intervention in fibrogenesis with its serious clinical
      consequences requires analysis of structure and cellular sources of ECM.
      Fibronectin (FN) is a high molecular weight glycoprotein and increases first
      among ECM proteins during liver fibrosis. The following report summarizes the
      crucial aspects of FN during fibrogenesis. Besides its controvertible role as
      initiator or regulator of fibrogenesis FN plays an important role as a scaffold
      for other matrix proteins.

PMID- 8309340
TI  - [Alcohol abuse as a cause of illness in an internal medicine department with
      emphasis on gastroenterology and hepatology].
AB  - The percentage and spectrum of alcohol-induced diseases were determined in 200
      male and female patients. In 28 percent of the men and 8 percent of the women,
      inpatient treatment had been necessitated in the first instance by alcohol
      induced diseases. In both men and women abusing alcohol, the percentage of
      younger patients was appreciably higher than in patients who did not abuse
      alcohol. Among male drinkers, the most common pathologies diagnosed were diseases
      of the liver (78.6%), the upper gastrointestinal tract, the pancreas (51.7%) and
      the central nervous system (42%), as well as cardiovascular diseases (23.2%). The
      majority of male patients abusing alcohol had two or more organic diseases (80%).
      In 35.4%, three or more different diseases were diagnosed. Among female patients
      abusing alcohol, the pattern of the various diseases was largely identical with
      that seen among the male patients. The duration of hospitalisation was
      appreciably longer in male drinkers (mean +/- SD = 14.1 +/- 10.1 days). Among
      male drinkers 51.8%, and among female drinkers 68.7%, were also heavy smokers. Of
      the 144 men in whom alcohol abuse was not certain, 30 were heavy smokers and, in
      the main, were being treated for cardiac and/or bronchopulmonary diseases. It is
      highly probable that, owing to the nature of the evaluation employed, the
      percentages of patients abusing alcohol or nicotine were underestimated. The fact
      that a high 43% of mainly younger male patients presented with diseases that
      could be traced back mainly or solely to alcohol or tobacco consumption, together
      with the multimorbidity and chronicity of the diseases of these patients
      underscores the urgent need to attach more importance to promoting preventive
      measures.

PMID- 8309341
TI  - [The knowledge base of the Hepaxpert I System: automatic interpretation of
      Hepatitis A and B serology].
AB  - The knowledge base of Hepaxpert-I, a medical expert system for interpretive
      analysis of hepatitis A and B serologic findings, contains 13 rules for hepatitis
      A and 106 rules for hepatitis B serology. Formally, the construction of the
      knowledge base was done by forming a partition of the sets of possible serologic
      finding patterns--64 for hepatitis A and 4096 for hepatitis B serology--induced
      by an equivalence relation, divides the elements of the sets into disjoint
      subsets, the equivalence classes. Each equivalence class is represented as one If
      Then rule that assigns to every member of the equivalence class one interpretive
      text. The partition of the possible finding patterns into equivalence classes and
      the disposal of one and only one interpretive text for each equivalence class
      made the creation of a very practical and efficient computer program for the
      precise interpretation of any finding pattern of serologic tests for hepatitis A
      and B possible. The complete set of the provided If-Then rules is represented in
      this paper.

PMID- 8309342
TI  - [Diffuse pseudo-diverticulosis of the esophagus with severe cranial stricture,
      axial hiatal hernia and Barrett syndrome].
AB  - We report about a patient with esophageal intramural pseudodiverticulosis (EIP)
      who was referred to our department for further investigation of dysphagia. EIP is
      a rare, pathologically well defined disease, most frequently characterized by
      stricture-associated symptoms. The diagnosis of EIP is made by barium swallow and
      can be confirmed by endoscopy which shows typical diverticula-like changes of the
      esophageal wall.

PMID- 8309343
TI  - [Gastrointestinal endoscopic studies in ambulatory practice].

PMID- 8309344
TI  - [Physician-patient seminar: physicians and patients discuss gastrointestinal
      diseases].

PMID- 8309345
TI  - Evidence for delta opioid receptor subtypes regulating adenylyl cyclase activity
      in rat brain.
AB  - Opioid agonists selective for mu- or delta opioid receptors inhibit adenylyl
      cyclase in membranes from rat caudate-putamen and nucleus accumbens. The presence
      of subtypes of delta opioid receptors has been suggested. In both brain regions
      we have found that the inhibition of adenylyl cyclase by DPDPE was more readily
      antagonized by 7-benzylidenenaltrexone (BNTX), than by naltriben. In contrast,
      the inhibitory effects of deltorphin-II and DSLET were more readily antagonized
      by naltriben, than by BNTX. Neither naltriben nor BNTX significantly antagonized
      the effect of a mu selective agonist. These results suggest that inhibition of
      adenylyl cyclase in caudate-putamen and nucleus accumbens is regulated by two
      forms of delta-opioid receptor with ligand selectivities similar to those two
      forms proposed to mediate analgesic effect.

PMID- 8309346
TI  - SR 48692, a non-peptide neurotensin receptor antagonist, blocks the
      cardiovascular effects elicited by neurotensin in guinea pigs.
AB  - In guinea pigs anaesthetized with sodium pentobarbital, SR 48692, a non peptide
      neurotensin receptor antagonist blunted the blood pressure increase induced by
      exogenous neurotensin in a dose dependent manner. Furthermore, in isolated
      spontaneously beating guinea pig atria, both the tachycardia and inotropic
      responses induced by neurotensin were potently antagonized. SR 48692 did not show
      any intrinsic effect in vivo or in vitro.

PMID- 8309347
TI  - TGF alpha-PE40 inhibits non-small cell lung cancer growth.
AB  - The ability of a chimeric toxin containing transforming growth factor alpha (TGF
      alpha) and truncated Pseudomonas exotoxin A to inhibit NSCLC growth was
      investigated. TGF alpha-PE40 inhibited binding of 125I-EGF to NSCLC cell lines
      with an IC50 value of 0.5-3 micrograms/ml. Similarly, other forms of the fusion
      protein, TGF alpha-PE38 and TGF alpha-PE40Asp553, which have active TGF alpha
      binding domains, inhibited specific 125I-EGF binding to NSCLC cells with IC50
      values of 0.1-2 and 0.05-05 microgram/ml respectively. TGF alpha-PE40 inhibited
      35S-methionine uptake by NSCLC cells with an ED50 value of 1-30 ng/ml. TGF alpha
      PE38, which has one of the two disulfide pairs of PE40, inhibited amino acid
      uptake with ED50 values of 3-50 ng/ml whereas TGF alpha-PE40Asp553, which lacks
      ADP ribosylation activity, had an ED50 > 100 ng/ml. TGF alpha-PE40 inhibited
      colony formation of NSCLC cells with an LD50 value of 0.008-0.1 ng/ml. Similarly,
      TGF alpha-PE38 inhibited NSCLC colony formation with LD50 values of 0.002-0.1
      ng/ml whereas TGF alpha-PE40Asp553 had an LD50 > 10 ng/ml. Also, TGF alpha-PE40
      and TGF alpha-PE38 inhibited NSCLC xenograft formation in nude mice whereas TGF
      alpha-PE40Asp553 was inactive. These data suggest that TGF alpha-PE40 and TGF
      alpha-PE38 may be useful agents to inactivate NSCLC cells.

PMID- 8309348
TI  - Decreased prostacyclin production by liver non-parenchymal cells precedes liver
      injury in experimental alcoholic liver disease.
AB  - We used the intragastric feeding rat model for alcoholic liver disease to
      investigate the relationship between prostacyclin and liver injury. Rats were fed
      the following diets for periods ranging from 1 to 8 weeks: corn oil plus ethanol
      (CO+E), corn oil plus dextrose (CO+D), saturated fat plus ethanol (SF+E) and
      saturated fat plus dextrose (SF+D). Prostacyclin production (assessed by 6
      ketoprostaglandin F1 alpha) by liver non-parenchymal cells decreased steadily
      over the 8 week period in animals fed CO+E (liver injury present) whereas in
      animals fed SF+E (no liver injury) there was no change in prostacyclin
      production. Plasma levels of 6-ketoprostaglandin F1 alpha were also significantly
      lower in the CO+E group compared to the other groups studied. We propose that
      decreased prostacyclin production by liver non-parenchymal cells may contribute
      to the hepatotoxic effect of ethanol.

PMID- 8309349
TI  - Effects of MR889, a cyclic thiolic neutrophil elastase inhibitor, on rheologic
      properties of mucus.
AB  - MR889 is a synthetic inhibitor of human neutrophil elastase with potential in
      clinical conditions characterized by a high load of this proteolytic enzyme,
      mainly chronic obstructive pulmonary disease. On the basis of its mechanism of
      inhibition, it has been suggested that MR889, upon reaction with elastase, would
      generate new free thiol groups. The aim of this study was to investigate whether
      MR889, upon reaction with elastase, may modify rheologic properties, i.e.
      apparent viscosity and elasticity, of both human sputum and porcine stomach
      mucus, in ex-vivo and in vitro experiments. MR889 10(-4) M alone had no effect on
      rheologic properties of samples, whereas an agent with free thiol group, n
      acetylcysteine 10(-4) M reduced both viscosity and elasticity. MR889 10(-4) M
      upon reaction with elastase 0.03 nMol (giving 83% of elastase inhibition) had no
      effect on rheologic properties of samples, whereas upon reaction with elastase
      0.15 nMol (49% inhibition) yielded a marked decrease in viscosity. This result
      would suggest that MR889, in the presence of a high load of elastase, may acquire
      direct mucus modifying capacity, likely because of its greater utilization upon
      reaction with the enzyme.

PMID- 8309350
TI  - Development of a model for Parkinson's disease in sheep using unilateral
      intracarotid injection of MPTP via slow continuous infusion.
AB  - The effects of unilateral intracarotid administration of MPTP (1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine) in sheep were studied with the goal of producing a
      non-primate, large animal model of Parkinson's Disease. Adult female sheep were
      given an acute (over 30 min) or chronic (over 1 week) injection of MPTP (0.4-5.0
      mg/kg) via the common carotid artery. Both methods produced parkinsonian-like
      behavior. Turning contralateral to the side of injection was induced by
      apomorphine (APO) in both groups. However, amphetamine (AMP) induced ipsilateral
      turning only in the chronic treatment group. Acute and chronic MPTP treatment
      resulted in a loss of substantia nigra tyrosine hydroxylase immunoreactive (THIR)
      neurons with a significantly greater loss ipsilateral to the injection in each
      treatment group (acute p < 0.05; chronic p < 0.01). Caudate dopamine (DA) was
      depleted in both treatment groups, although the difference between ipsilateral
      and contralateral DA content was significant only in the chronic treatment group
      (p < 0.05). The best results were seen in those animals with chronic infusion
      with the occipital artery occluded to prevent entry of drug into the posterior
      circulation with subsequent bilateral distribution. Use of slow and continuous
      intracarotid administration of MPTP with the ipsilateral occipital artery
      occluded can prevent some of the bilateral effects of acute treatment, and
      results in statistically significant ipsilateral reduction of THIR neurons in the
      substantia nigra and reduction of tissue levels of DA in the caudate nucleus.
      Such treatment produces appropriate turning responses to both AMP and APO
      challenge not seen in the acute treatment group, and appears to be an effective
      method of producing parkinsonian-like behavior in a large animal.

PMID- 8309351
TI  - Anti-obesity and anti-diabetic effects of CL 316,243, a highly specific beta 3
      adrenoceptor agonist, in yellow KK mice.
AB  - The anti-obesity and anti-diabetic effects of CL 316,243, a highly specific beta
      3-adrenoceptor agonist (beta 1: beta 2: beta 3 = 0:1:100,000), were evaluated in
      obese diabetic yellow KK mice and C57Bl control mice. The study compound was fed
      through a gastric tube at a rate of 0.1 mg/kg/day for 2 weeks. The following
      parameters were compared in the treated and control animals given distilled
      water: brown adipose tissue thermogenesis, resting metabolic rate, insulin
      receptors in adipocytes, and blood glucose and serum insulin levels during a
      glucose overloading test. CL 316,243 significantly increased brown adipose tissue
      thermogenesis and resting metabolic rate in both yellow KK mice and C57Bl
      controls. The amount of white adipose tissue decreased, although food intake was
      not affected. The effects contributed to the mitigation of obesity in yellow KK
      mice. CL 316,243 also increased the concentration of insulin receptors and
      decreased the levels of serum insulin and blood glucose during the glucose
      overloading test in yellow KK mice. These observations suggest that CL 316,243
      possesses anti-obesity and anti-diabetic effects and consequently may be useful
      for treating obesity as well as non-insulin-dependent diabetes mellitus in obese
      persons, without causing excessive side effects.

PMID- 8309352
TI  - Tauro alpha-muricholate has a biliary transport maximum (Tm) value equivalent to
      that for tauroursodeoxycholate and tauro beta-muricholate in the rat.
AB  - Our previous studies have shown that Tm values for tauroursodeoxycholate (TUDC)
      and tauro beta-muricholate (T beta-MC) are more than two-fold higher than that
      for taurocholate (TC) in the rat. The present study attempted to clarify whether
      tauro alpha-muricholate (T alpha-MC) also has such an unusually large Tm value in
      the rat. Under nembutal anesthesia, male Wistar derived rats (body weight 280-300
      g, 13 wks in age) were continuously infused with T alpha-MC solution. The
      infusion rate was raised stepwise every 20 min, until the bile flow began to
      decline. Bile was collected every 10 min and bile salt excretion rate was
      determined. The average of the highest three excretion values was assumed to be
      the Tm in each animal. The Tm value of T alpha-MC was found to be 2.86 +/- 0.36
      mumol/min/100 g (mean +/- SD, n = 4), which was even greater than Tm values for
      TUDC (2.59 +/- 0.39 mumol/min/100 g, n = 4) and T beta-MC (1.93 +/- 0.31
      mumol/min/100 g, n = 4) as we reported previously. The relationship between the
      bile flow rate (microliter/min/100 g, Y axis) and bile salt excretion rate
      (mumol/min/100 g, X axis) was highly linear [Y = (6.00 +/- 0.29) x +(6.60 +/-
      1.88), P < 0.001, r = 0.95, n = 54]. The slope value for T alpha-MC (6.00 +/-
      0.29 microliters/mumol) was significantly higher than that for TUDC (4.76 +/-
      0.71 microliters/mumol) and was comparable to that for T beta-MC as we previously
      found for these bile salts in this rat strain. The results suggest that T alpha
      MC has a very efficient transport system in this species as was observed for the
      other two bile salts that have a 7 beta-hydroxy group (TUDC and T beta-MC). This
      efficient transport system thus appears to be shared not only by bile salts
      specifically having a 7 beta-hydroxy group, but also by other bile salts such as
      T alpha-MC that have a 6 beta-hydroxy group but not a 7 beta-hydroxy group.

PMID- 8309353
TI  - Experimentally induced Mycoplasma pneumoniae pneumonia in chimpanzees.
AB  - Eight chimpanzees were examined. Two served as negative control and six
      inoculated with Mycoplasma pneumoniae became colonized. Colonization persisted
      for 28-68, 16-50 and 21 days with an average duration of 47, 32.5 and 21 days in
      the oropharyngeal, tracheal and lung tissues, respectively. Mycoplasma titers
      ranged from 10(8) to 10(1) color-changing units per specimen during the course of
      the infections. Seroconversion occurred within 12-15 days and peak antibody
      titers ranged from 1.256 to 1.1024 and developed between days 28 and 48 post
      inoculation. Positive cold agglutinin titers were detected between 12 to 15 days
      and peak titers ranged from 1:80 to 1:640. Significant increases in sIgA and IgG
      immunoglobulin antibody levels were detected in lung lavage fluids. Unlike the
      many other experimentally infected animals examined, chimpanzees infected with M.
      pneumoniae had positive X-ray findings, developed cold agglutinins and showed
      overt signs of disease. These signs include persistent cough, low grade fever,
      rhinitis, oropharyngitis, diarrhea, and loss of appetite. Peak severity of
      disease corresponded with peak lung colonization, and the detection of cold
      agglutinins and positive X-ray findings. The microbiological, serological and
      clinical aspects of pneumonia induced in chimpanzees was similar to naturally
      occurring primary atypical pneumonia in humans.

PMID- 8309354
TI  - Cloning and characterization of three hemolysin genes from Aeromonas salmonicida.
AB  - Two hemolysin genes (ASH3 and ASH4) of Aeromonas salmonicida strain 17-2 and one
      (ASH1) of A. salmonicida ATCC14174 were cloned into the cosmid vector charomid 9
      36 in Escherichia coli DH1. The overall amino acid sequence of the ASH3 was
      similar to that of the aerolysins of Aeromonas hydrophila and Aeromonas sobria,
      and hemolysins AHH3, AHH4, and AHH5 of A. hydrophila, and hemolysin ASA1 of A.
      sobria. The sequence of ASH4 was similar to that of the AHH1 hemolysin of A.
      hydrophila. The ASH4 hemolysin contains some homologous sequence regions of the
      Vibrio vulnificus and Vibrio cholerae cytolysin-hemolysin. Both ASH3 and ASH4 DNA
      probes reacted with all 104 strains of A. salmonicida, whereas the ASH1 DNA probe
      did not hybridize with any of the 104 strains studied except strain ATCC14174.
      ASH1 and ASH3 were broad spectrum hemolysins with most activity against rabbit
      and horse erythrocytes, respectively, whereas ASH4 hemolysin did not lyse bovine
      and horse erythrocytes. ASH3 and ASH4, but not ASH1, were activated by trypsin.

PMID- 8309355
TI  - Experimental infection of Chlamydia pneumoniae in mice.
AB  - NIH/S, Swiss Webster, and BALB/c mice were infected intranasally with three
      Chlamydia pneumoniae isolates, Kajaani 6, Helsinki 12, and TW-183. C. pneumoniae
      could be isolated from the lung homogenates and bronchoalveolar lavage fluids up
      to the third week post-infection. Specific serum IgG antibodies against C.
      pneumoniae reached high levels in the third week and remained elevated until the
      end of the 6-week follow-up period. Serum IgM levels were highest in the third
      week post-infection and started to decrease thereafter. In spite of these signs
      of ongoing infection, the mice did not show any symptoms of disease. NIH/S mice
      could be readily and uniformly infected, while BALB/c mice were the most
      resistant and developed the weakest antibody response. The greatest histological
      changes were detected in NIH/S mice as well. The inflammatory infiltrate, which
      consisted of lymphocytes and plasma cells throughout the study, was restricted to
      the peribronchial and perivascular space and to the interstitium of the lung
      parenchyma.

PMID- 8309356
TI  - Streptokinase gene polymorphism in group A streptococci isolated from Ethiopian
      children with various disease manifestations.
AB  - Certain variants of streptokinase from group A streptococci have been associated
      with acute post-streptococcal glomerulonephritis (APSGN). The streptokinase gene
      (ska) has previously been grouped into nine different polymorphic genotypes of
      which ska1, ska2, ska6, and ska9 were identified in group A streptococci
      associated with clinical and experimental APSGN. A total of 53 group A
      streptococci isolated from Ethiopian children: five from acute rheumatic fever,
      18 from APSGN, ten each from tonsillitis, impetigo and healthy carriers, were
      analyzed for ska gene polymorphism using polymerase chain reaction (PCR) and
      restriction enzyme analysis. The frequency of the nephritis-associated
      streptokinase genotypes was 83% among the APSGN isolates and 74% in the non-ASPGN
      isolates. ska2 was the most commonly found genotype with a frequency of 64% among
      all isolates, 66% among the APSGN isolates, and 63% among the non-APSGN isolates.
      ska1 was identified in 13% among all isolates and 17% among the APSGN isolates.
      Seventeen non-APSGN isolates from Scandinavian countries were studied for
      comparison and all carried either ska1 or ska2. The other nephritis-associated
      ska6 and ska9 were not detected among the 53 Ethiopian isolates. ska1 was
      exclusively associated with serum opacity reaction (SOR) producers. ska2 was
      evenly distributed among SOR-positive and SOR-negative isolates. The other
      genotypes were detected only among SOR-negative strains. The findings of the
      present study showed an even distribution of the nephritis-associated
      streptokinase gene among group A streptococcal isolates with no correlation to
      disease pattern. Thus additional factors must also be operative in the
      pathogenesis of APSGN.

PMID- 8309357
TI  - The role of a 40-megadalton plasmid in the adherence and hemolytic properties of
      Aeromonas hydrophila.
AB  - A cured strain of Aeromonas hydrophila, MS-2PC, was examined for phenotypic
      changes in antibiotic resistance, adherence, and hemolysis. Parental strain MS-2
      was resistant to ampicillin, novobiocin, and carbenicillin; MS-2PC, which lacked
      a 40-MDa plasmid, was also resistant to ampicillin but was sensitive to
      novobiocin and carbenicillin. The adherence of these isolates to CaCo-2 and HeLa
      cells was examined. MS-2PC demonstrated greater attachment to both cell lines
      than did strain MS-2 (p < 0.05). MS-2PC also demonstrated greater hemolysis
      activity than did MS-2 (p < 0.01). The 40-Mda plasmid was isolated and
      reintroduced into MS-2PC. The resulting transformant, 20T, regained resistance to
      carbenicillin and novobiocin. The attachment ability of 20T was equal to that of
      MS-2, and both strains demonstrated significantly lower attachment ability than
      that of MS-2PC (p < 0.01). Strains MS-2 and 20T exhibited the same hemolysis
      pattern, which was markedly less than that of strain MS-2PC. These results
      indicate that the 40-Mda plasmid which codes for antibiotic resistance also
      controls other functions of A. hydrophila MS-2.

PMID- 8309358
TI  - Expression of an immunoreactive 72 kDa protein in strains of Haemophilus
      influenzae biogroup aegyptius associated with Brazilian purpuric fever.
AB  - Brazilian purpuric fever (BPF) is a newly described pediatric syndrome that
      results in significant morbidity and mortality. BPF is caused by specific
      phenotypic strains of Haemophilus influenzae biogroup aegyptius that are capable
      of intravascular survival. Immunoblotting of outer membrane proteins of H.
      influenzae biogroup aegyptius with normal human serum showed that most virulent
      strains of H. influenzae biogroup aegyptius associated with BPF expressed an
      immunologically prominent protein at 72 kDa. A corresponding protein in avirulent
      isolates migrated at 79 kDa. Although a minor component on SDS-PAGE analysis of
      the outer membrane, specific antibody against this protein is present in high
      concentrations in normal human serum.

PMID- 8309359
TI  - Dermopathy of Graves disease (pretibial myxedema). Review of 150 cases.
AB  - Pretibial myxedema is an uncommon manifestation of Graves disease, and little
      information is available regarding its natural course and its relation to other
      manifestations of Graves disease. We reviewed 150 consecutive cases with the
      diagnosis of pretibial myxedema over a 20-year period in a referral center. Only
      1 patient in this group did not have ophthalmopathy, whereas 88% had significant
      proptosis and 30% required orbital decompression surgery. Dermopathy was a late
      manifestation of Graves disease, and its onset usually followed the diagnosis of
      hyperthyroidism and ophthalmopathy. In a few patients, dermopathy preceded
      diagnosis of hyperthyroidism or onset of ophthalmopathy. Fourteen patients were
      never clinically hyperthyroid; spontaneous hypothyroidism had developed in 11 in
      this group. All cases involved the lower extremities, with only 1 patient having
      combined upper and lower extremity involvement. The most common form of thyroid
      dermopathy was nonpitting edema, followed by nodular and plaque forms, which
      occurred with equal frequency. The polypoid form occurred in 1 patient and the
      elephantiasic form in another; 7.3% had thyroid acropachy. Follow-up was
      available for 120 patients (range, 3 mo to 19 yr; mean, 3.2 yr), and complete
      remission was observed in only 12 patients. Topically applied corticosteroid
      therapy was used in 76 patients, and in this group 38% had sustained long-term
      partial remission, as opposed to 18% in the group receiving no corticosteroid
      therapy.

PMID- 8309361
TI  - Neurocysticercosis in Houston, Texas. A report of 112 cases.
AB  - Neurocysticercosis (NCC) is a common disease among Hispanic immigrants to the
      American Southwest. The experience in this series suggests a higher incidence of
      disease than has been reported by public health personnel. Symptoms at
      presentation correlate with the anatomic site of disease. Parenchymal disease and
      inactive calcifications present primarily with seizures; ventricular disease with
      headaches and symptoms of acute hydrocephalus; and cisternal disease with basilar
      meningitis, hydrocephalus, or seizures from coexisting parenchymal disease.
      Current treatment regimens are suboptimal, although symptoms may resolve in the
      absence of therapy. Patients may not respond to a single course of praziquantel
      therapy. Procedures to divert cerebrospinal fluid are often needed and frequently
      require revision. We found an association between corticosteroid treatment and
      the need for repeat therapy with praziquantel, but controlled studies are needed
      to clarify the role of antiparasitic agents in all forms of neurocysticercosis.

PMID- 8309360
TI  - Hepatic outflow obstruction (Budd-Chiari syndrome). Experience with 177 patients
      and a review of the literature.
AB  - Budd-Chiari syndrome (BCS) may not be as uncommon as was once believed. Our study
      has substantiated the existence of 2 major clinical forms. The acute syndrome is
      invariably associated with extensive blockage of the major hepatic veins,
      resulting in congestive liver cell necrosis. In a small, but significant, number
      of patients the inferior vena cava (IVC) is also occluded. The important
      etiologic factors are related to hypercoagulability of blood. Immediate placement
      of a shunt improves survival. The chronic syndrome is characterized by portal
      hypertension and is associated with a variable abnormal vascular anatomy. The
      causes of the chronic syndrome are not clear, but a substantial number of cases
      are related to the presence of an IVC membrane. Shunt surgery is effective but
      procedures aimed at the primary pathology are likely to be even more so. The
      natural history of BCS should be viewed over a long period of time. The very long
      survival of several patients urges a more cautious approach to surgical remedies.
      Budd-Chiari syndrome probably represents a spectrum of disease caused primarily
      by a hypercoagulable state and having a varied presentation depending on the
      balance between rate of formation and the extent of the thrombosis and the body's
      own rate of thrombolysis and recanalization. The extent and efficacy of the
      individual's collateral circulation and the rate of development of liver fibrosis
      are other determinants. It is thus possible to view BCS as a continuum of a
      single pathogenetic spectrum. Pregnancy-related BCS in India probably has strong
      social determinants, and is usually acute and fulminant. We have, however,
      documented a chronic form not described earlier. Children usually do not have
      acute BCS, but chronic BCS in children and adolescents is similar to that in
      adults. Membranous obstruction of the inferior vena cava (MOVC) is common and was
      found even at a young age. The association of MOVC with hepatocellular carcinoma,
      however, did not appear to be as clear as was previously believed. There has been
      a wide geographical variability in the causes and manifestations of BCS. Our
      study has clearly shown that--Kipling's categorical statement to the contrary-
      East and West do meet in India, in the Budd-Chiari syndrome.

PMID- 8309362
TI  - Mixed cryoglobulinemia in chronic hepatitis C infection. A clinicopathologic
      analysis of 10 cases and review of recent literature.
AB  - We present 10 cases of mixed cryoglobulinemia in patients infected with hepatitis
      C, including pertinent clinical, serologic, and pathological data. The findings
      attributable to MC appear to be similar in patients who are HCV-infected as in
      those with unknown HCV status. The prevalence of MC in HCV-infected patients
      appears to be lower in our region (13%) than in southern Europe (50-90%) although
      some of this difference is due to our requirement that patients included in our
      study have a cryocrit of at least 5%. In our patients, cryoglobulins were shown
      to be deposited in skin and kidney, but not in liver. The mechanisms by which HCV
      and MC are related remain uncertain. Although we and others have evidence for
      enrichment of HCV RNA in the cryoprecipitates of some patients, this was not
      always the case, and it is not yet clear that this finding is of fundamental
      pathogenic importance. Finally, it appears that some patients with HCV and MC may
      have a beneficial clinical response of vasculitic symptoms to therapy with alpha
      interferon, as well as to glucocorticoids or other immunosuppressants. In our
      group, no predictors were apparent to distinguish responders from nonresponders
      before treatment. Similarly, the duration of response remains to be determined.

PMID- 8309363
TI  - Pancreatitis in patients with end-stage renal disease.
AB  - In a population of 716 patients with end-stage renal disease (ESRD), 46 patients
      (6.4%) were identified as having pancreatitis. Pancreatitis was significantly
      more common in those with alcohol abuse, systemic lupus erythematosus (SLE), and
      polycystic kidney disease. It was not significantly associated with
      hyperlipidemia, biliary tract disease, or hypercalcemia. Acute pancreatitis
      occurring before the patient developed ESRD was mainly alcohol-related and did
      not appear to be a significant risk factor for future episodes of pancreatitis
      during dialysis. Chronic calcific pancreatitis diagnosed before ESRD was almost
      invariably due to alcohol abuse, and tended to be a marker for recurrent acute
      exacerbation after development of ESRD, whether alcohol consumption continued or
      not. Pancreatitis occurring for the first time after ESRD in patients on dialysis
      was generally benign, and was usually accompanied by an uneventful recovery and
      few recurrent episodes. However, a significant elevation of the calcium x
      phosphate product was observed in these patients, occurring in about half the
      patients without any known precipitating factor. After kidney transplantation,
      the development of pancreatitis was associated with higher morbidity and
      mortality. Chronic calcific pancreatitis diagnosed after ESRD occurred only in
      patients with SLE; reported here for the first time, it may be a manifestation of
      long-standing disease, chronic steroid therapy, or both.

PMID- 8309364
TI  - X-ray crystallography of proteins.

PMID- 8309365
TI  - Quantitative fluorescence imaging techniques for the study of organization and
      signaling mechanisms in cells.

PMID- 8309366
TI  - Automated enzyme assays.

PMID- 8309367
TI  - Rapid-scanning stopped-flow spectrophotometry.

PMID- 8309368
TI  - Epilepsy in pregnancy: neural tube defects and folate.

PMID- 8309369
TI  - An evaluation of laparoscopic versus open cholecystectomy.
AB  - OBJECTIVE: To compare open cholecystectomy (OC) with laparoscopic cholecystectomy
      (LC) in terms of clinical aspects and a limited review of costs. SETTING: The
      Austin Hospital, Melbourne, a university teaching hospital. DESIGN: Prospective
      LC patients were compared with a retrospective group of OC patients whose surgery
      had been performed by the same surgeons. METHODS: Consecutive patients undergoing
      LC were interviewed, their medical records were analysed and the cost of their
      hospitalisation was assessed. Similar data, collected previously from patients
      undergoing OC, were used for comparison. RESULTS: There were 108 patients in each
      group, 93.5% treated electively. All had gallstones. No deaths or common bile
      duct injury occurred. The mean operating room time was 131 +/- 3.7 minutes for OC
      and 164 +/- 4.7 minutes for LC. Operative cholangiography was attempted in 80% in
      each group, being successful when attempted in all OCs and in 95% of LCs. The
      conversion rate of LCs to OCs was 4.5%. Minor complications were more frequent
      with OCs. The mean duration of hospital stay was 6.5 +/- 0.3 days for OCs and 2.0
      +/- 0.2 days for LCs. The amount and period of analgesia were significantly less
      in the LC group. Patients recovered significantly faster after LC (P < 0.01)
      during the first eight weeks after surgery. There was no difference by 12 weeks.
      The overall cost for each LC was $838 less than OC for the entire hospital stay.
      CONCLUSION: These results support the view that LC is a safe and justified
      replacement for OC in the elective situation, with benefits to the patient,
      hospital and general community. The hospital cost for LC was less than for OC.

PMID- 8309371
TI  - Adequacy of control of asthma in a general practice. Is maximum peak expiratory
      flow rate a valid index of asthma severity?
AB  - OBJECTIVES: To evaluate the adequacy of control of asthma in patients attending a
      general practice; and to examine the validity of peak expiratory flow rate (PEFR)
      as an index of asthma severity in the context of general practice. DESIGN: Short
      term cohort study using indices derived from two weeks of peak flow monitoring to
      evaluate asthma control. PARTICIPANTS: Known and newly diagnosed asthmatics aged
      six years or more who presented during the study period for any reason. They were
      enrolled if baseline forced expiratory volume in one second (FEV1) increased by
      10% or more after the administration of nebulised salbutamol. Children under the
      age of 12 years with no initial response to bronchodilator were included if an
      exercise test performed on another day was positive. OUTCOME MEASURES: Peak flow
      criteria for "mild asthma" in the Asthma Management Plan, 1989 (Med J Aust 1989;
      151: 650-653) were used as the initial definition of "adequate control". The
      definition of "adequate control" was modified to variability less than 20% and a
      minimum PEFR of 50% or more of mean predicted value. RESULTS: There was no
      association between variability and maximum PEFR, but variability was strongly
      correlated with minimum PEFR (R = -0.60; P < 0.0005). Asthma was adequately
      controlled in 68% of the participants. CONCLUSION: Current guidelines with
      respect to the peak flow indices used in the classification of the severity of
      asthma need to be re-evaluated and probably changed for application in general
      practice.

PMID- 8309370
TI  - Ethical issues in Australian hospitals.
AB  - OBJECTIVE: To identify the most common ethical issues of concern in Australian
      hospitals. DESIGN: A descriptive study using data collected by means of a
      questionnaire. PARTICIPANTS: Seven hundred and thirty-nine (74%) hospital
      administrators and employees nominated by hospital administrators in Australian
      public and private hospitals. RESULTS: Over half the respondents reported that
      ethical concerns had been raised in relation to: making "not for resuscitation
      orders"; the treatment of patients with HIV and AIDS; interprofessional conflict;
      and the allocation of resources. CONCLUSION: "End of life" concerns, patient
      autonomy issues, questions of resource distribution, and communication
      difficulties commonly raise ethical concerns in Australian hospitals.

PMID- 8309372
TI  - Educational support for overseas-trained doctors.
AB  - Overseas-trained doctors face a number of obstacles in the process of seeking to
      become registered to practise medicine in Australia. Educational support programs
      have been developed in all states to assist overseas-trained doctors to prepare
      for the examinations of the Australian Medical Council. We describe our
      experiences in providing such support and detail the educational needs we have
      identified of overseas-trained doctors migrating to Australia.

PMID- 8309373
TI  - Anticoagulants and antiplatelet drugs.

PMID- 8309374
TI  - Cardiology.

PMID- 8309375
TI  - Vitamin K and childhood cancer.

PMID- 8309376
TI  - ACE inhibition and lateral thinking.

PMID- 8309377
TI  - The reform of medical education.

PMID- 8309378
TI  - Cerebrovascular accident after taipan bite.

PMID- 8309379
TI  - Congenital syphilis: when the medium fails to transmit the message.

PMID- 8309380
TI  - Postpartum haemorrhoids--evaluation of a cooling device (Anurex) for relief of
      symptoms.

PMID- 8309381
TI  - Resource restraints: what do we tell our patients?

PMID- 8309382
TI  - Hearing impairment and hearing aid use in women over 65 years of age.

PMID- 8309383
TI  - Antiphospholipid antibodies.

PMID- 8309384
TI  - The public health problem of environmental lead exposure.

PMID- 8309385
TI  - Abstinence and Antabuse: symbolism and supervision.

PMID- 8309386
TI  - Petrol sniffing down the track.

PMID- 8309387
TI  - Petrol sniffer's encephalopathy. A study of 25 patients.
AB  - OBJECTIVES: To determine the clinical features, response to treatment and outcome
      of petrol sniffers presenting to Perth's teaching hospitals. DESIGN:
      Retrospective study of all admissions to Perth's tertiary referral hospitals that
      were related to petrol sniffing from 1 January 1984 to 31 December 1991. RESULTS:
      Twenty-five patients (22 male and 3 female) were admitted with a diagnosis of
      intentional petrol sniffing. Five presented with acute petrol intoxication as the
      result of an isolated action. The remaining 20 patients were "chronic petrol
      sniffers". The mean age was 17.7 years (range, 5-27 years). Twenty patients were
      Australian Aborigines, including 18 of 20 chronic petrol sniffers and the three
      females. In the chronic petrol sniffers, a high prevalence of seizures and an
      alarmingly high case fatality ratio (8 of 20), usually by sudden death, were
      found. An altered mental state was universal, manifesting as drowsiness, delirium
      or stupor. Generalised tonic-clonic seizures occurred in 14, three with status
      epilepticus. Myoclonus (9), chorea (8) and cerebellar ataxia (appendicular and
      truncal) (13) were common. High blood lead levels on presentation were associated
      with a poor prognosis (survivors v. deaths, P = 0.002). Eighteen of the 20
      patients were treated with specific agents to reduce the lead load, but the
      results were extremely disappointing. CONCLUSION: Petrol sniffing is an important
      cause of sickness and death in young people from some rural Aboriginal
      communities. It can cause sudden death or irreversible encephalopathy. Those
      severely affected have a poor prognosis, despite treatment. Effective strategies
      for prevention are needed.

PMID- 8309388
TI  - Upper gastrointestinal endoscopy in central Australian aborigines.
AB  - OBJECTIVES: To examine the upper gastrointestinal endoscopic findings in
      Australian Aborigines in central Australia; to determine if peptic ulceration
      occurs in this group; and to discover whether this population shares Helicobacter
      pylori as a risk factor for peptic ulceration. METHODS: A retrospective analysis
      of the records of all Aboriginal patients undergoing endoscopy at a general
      hospital over a two-year period. RESULTS: Eighty-five endoscopies were performed
      in 64 patients. Haematemesis and melaena was the indication for 24 patients (more
      commonly in men) and a cause was identified in 83% of these patients; varices
      were the cause in 17%. Pain was an indication for 25 patients (more commonly in
      females) and abnormalities were detected in 64%. Peptic ulceration was found in
      nine patients and a further 23 had gastritis or duodenitis. Cases of oesophageal,
      gastric and duodenal malignancy were seen, as well as late complications of
      simple diseases, including gastric outlet obstruction, oesophageal stricture and
      cholecystoduodenal fistula formation. Of 17 gastric biopsies with evidence of
      inflammation, H. pylori was found in 15 (88%). CONCLUSION: This, the first study
      of upper gastrointestinal endoscopy in Aborigines, shows its usefulness in the
      investigation of their gastrointestinal complaints. Oesophageal varices were
      found to be an important cause of bleeding. Peptic ulceration associated with H.
      pylori was found to be common.

PMID- 8309389
TI  - Aboriginal health and a new curriculum for rural doctors.

PMID- 8309390
TI  - The Journal's black record.

PMID- 8309391
TI  - The prevalence of tuberculosis infection among Year 8 schoolchildren in inner
      Sydney in 1992.
AB  - OBJECTIVE: To determine the prevalence of tuberculosis (TB) infection in Year 8
      schoolchildren (aged 12-14 years) in Sydney. DESIGN: Cross-sectional survey.
      SETTING: 22 inner city Sydney secondary schools. PARTICIPANTS: 2290 Year 8 school
      children enrolled in 1992. OUTCOME MEASURES: Distribution of Mantoux test
      reaction size and proportion of children who were Mantoux positive (i.e., having
      Mantoux reaction > or = 15 mm with previous Bacille Calmette-Guerin vaccination;
      > or = 10 mm without). RESULTS: Of the 2290 children, 1836 (81%) were screened
      and 1801 Mantoux reactions were read. Ten per cent of children were Mantoux
      positive--27% of foreign-born children and 2% of Australian-born children
      (relative risk 16.7, 95% confidence interval 10.6-26.4). Two children were found
      to have active TB disease. CONCLUSION: There is a high prevalence of primary (non
      contagious) TB infection in children aged 12-14 years in inner Sydney, mostly
      confined to children born overseas. Thus there is a large pool of infected
      children at risk of developing active (contagious) adult-type TB disease in the
      future. This public health problem should be addressed by identification and
      treatment of those infected.

PMID- 8309392
TI  - Antiarrhythmic drugs.

PMID- 8309393
TI  - Travel medicine. 2. Upon return.
AB  - The volume of international travel and diversity of destinations have increased
      dramatically in recent decades and continue to grow. The scope and variety of
      travel related health problems increase accordingly, with 15% to more than 50% of
      travellers to developing countries reporting some illness. Infections acquired
      abroad may be acute and life-threatening, requiring urgent, sometimes empirical,
      intervention. They may also be chronic and associated with late complications,
      particularly in immigrants, refugees and long term travellers. We present a
      perspective on and practical approach to the management of illness in returned
      travellers.

PMID- 8309394
TI  - Another kind of flying doctor.

PMID- 8309395
TI  - Antiphospholipid syndrome in pregnancy: a diagnostic dilemma.
AB  - OBJECTIVE: To present a case of severe pre-eclampsia in which diagnosis of the
      antiphospholipid syndrome was made after delivery, and to discuss pointers to the
      diagnosis. CLINICAL FEATURES: A 32-year-old woman in her second pregnancy
      presented at 32 weeks' gestation with severe pre-eclampsia. Her persisting severe
      postpartum illness was investigated. The presence of anticardiolipin antibodies
      and lupus anticoagulant led to the diagnosis of antiphospholipid syndrome.
      INTERVENTION AND OUTCOME: Induction of labour was successful, with delivery of a
      healthy baby girl. The patient made a full recovery after treatment with
      corticosteroids and warfarin. CONCLUSION: The antiphospholipid syndrome should be
      considered in cases of severe early pre-eclampsia.

PMID- 8309396
TI  - Inflammatory bowel disease--its history, current status and outlook.
AB  - In conclusion, it seems there has been a definite change in the epidemiology and
      course of IBD since earlier this century. Several points are worth emphasising:
      The diseases are relatively common, and there has been a general increase in
      their incidence, more so in some regions than others. The largest group affected
      is young adults, who will have their disease over several decades. This could
      potentially impact markedly on the workforce and on health care services. There
      is clearly a range of severity of this disease, and a greater number of mild
      cases have probably been diagnosed recently. This also helps to explain the
      differences in severity, need for surgery, and survival noted between community
      based studies and referral centre groups. Treatment has improved, particularly
      surgery (which usually takes place earlier on less critically ill patients),
      better operations, including continence surgery for most patients with UC and gut
      sparing procedures in Crohn's disease such as stricturoplasty. Medical management
      of acute disease has also improved which, in particular, has reduced mortality in
      elderly patients. Except for a subset of patients, life expectancy is close to
      normal, and time lost from the workforce, when considered in perspective over a
      working lifetime, is negligible. We can therefore be justifiably optimistic about
      the current long term outcome of IBD, and encourage our patients, their families
      and their employers to share in this outlook. With the promise of newer medical
      therapies on the horizon, prognosis may be further improved. Corticosteroids with
      little or no systemic side effects are currently in clinical trials and new anti
      inflammatory agents are being examined for their efficacy through prostaglandin,
      leukotriene, or oxygen free-radical inhibition. Now that mortality from IBD is
      largely a thing of the past, we need to concentrate our attention more closely on
      the associated morbidity. It is to be hoped that future long term studies attempt
      the difficult clinical measurements of morbidity and quality of life.

PMID- 8309397
TI  - Emergency medicine.

PMID- 8309398
TI  - Death from inadvertent chloroquine overdose.

PMID- 8309400
TI  - Vaccination against influenza infection.

PMID- 8309399
TI  - Neurocysticercosis.

PMID- 8309401
TI  - Putting back the bugs: bacterial treatment relieves chronic diarrhoea.

PMID- 8309402
TI  - Pseudobacteraemia with Pseudomonas fluorescens.

PMID- 8309404
TI  - Prospects for the treatment of obesity.

PMID- 8309403
TI  - The doctor and the clinic: young people's experiences of HIV testing.

PMID- 8309405
TI  - Asian adoptees in Western Australia.

PMID- 8309406
TI  - Medical psychiatric unit.

PMID- 8309407
TI  - Tea tree oil poisoning.

PMID- 8309408
TI  - The antimicrobial activity of tea tree oil.

PMID- 8309409
TI  - The investigation of chest pain: audit and intervention.

PMID- 8309410
TI  - Is cholesterol testing/treatment really beneficial?

PMID- 8309411
TI  - HTLV-I and clinical disease correlates in central Australian aborigines.

PMID- 8309412
TI  - Is cholesterol testing/treatment really beneficial?

PMID- 8309413
TI  - Cerebral palsy--reducing damages for medical indemnity.

PMID- 8309414
TI  - Decentralisation of assisted reproduction programs in Queensland and Victoria.

PMID- 8309415
TI  - Medicine and surgery inside the fallopian tube.

PMID- 8309416
TI  - Complications of laparoscopy.

PMID- 8309417
TI  - Laparoscopic hysterectomy: a series of 100 cases.

PMID- 8309418
TI  - [Misoprostol. Pharmacologic characterization and evaluation].

PMID- 8309419
TI  - [Phase-specific wound treatment. Application, function and use of wound
      dressings].

PMID- 8309420
TI  - [Prions--infectious particles or cytotoxic metabolites?].

PMID- 8309421
TI  - [Composition of fatty acids in foods].

PMID- 8309422
TI  - Characterization of porcine bone sialoprotein: primary structure and cellular
      expression.
AB  - Bone sialoprotein (BSP) is a highly glycosylated and sulphated phosphoprotein
      that is a major non-collagenous protein of bone. To further characterize the
      porcine protein and to study its expression during bone formation BSP cDNA clones
      were isolated from a porcine bone cDNA library. The primary sequence of the
      protein was derived from the nucleotide sequence of the largest cDNA insert and
      from the amino-terminal amino acid sequence determined by the automated Edman
      degradation procedure. When compared with sequences obtained from the human and
      rat BSPs 74% and 64% of the amino acids, respectively, were identical and a
      further 11% and 17%, respectively, were conservative replacements. Moreover, 60%
      of the amino acids in a concensus sequence derived from the primary sequences of
      mammalian BSPs were conserved with 16% conservative replacements. The two
      stretches of polyglutamic acid, through which the protein is capable of binding
      to hydroxyapatite, and an RGD motif that mediates cell attachment are retained in
      conserved sequences as are a number of potential sites of serine, threonine and
      tyrosine phosphorylation, glycosylation and tyrosine sulphation. Secondary
      structure prediction and hydrophilicity analysis indicate that the nascent BSP
      has an open flexible structure with the potential to form significant amounts of
      alpha-helix and some beta-sheet. In situ hybridization of fetal porcine bone with
      cRNA probes to porcine BSP mRNA shows that BSP is specifically expressed in
      differentiated osteoblasts on the surface of newly-forming bone trabeculae with
      especially high levels of hybridization at sites of de novo bone formation. The
      highly conserved features of BSP and its restricted distribution indicate an
      important role for this sialoprotein in the formation of bone.

PMID- 8309423
TI  - Hyaluronic acid modulates proliferation, collagen and protein synthesis of
      cultured fetal fibroblasts.
AB  - Fetal wound healing is characterized by minimal inflammation, mild fibroplasia
      and rapid, but organized collagen deposition such that scarring is not apparent.
      The matrices of fetal wounds differ greatly from adult wounds in that fetal
      wounds are persistently enriched with hyaluronic acid (HA). It has been shown
      that a reduction in fetal rabbit wound HA results in an adult-like healing
      response with increased fibroplasia and neovascularization. These observations
      suggest that HA can modulate cellular activity in fetal repair. Therefore, this
      study was designed to define the effect of HA on fetal fibroblast function.
      Fibroblasts from the skin of fetal rabbits were isolated and maintained in
      culture medium containing either no HA (controls), 1 microgram/ml, 10
      micrograms/ml or 100 micrograms/ml of HA (n = 6 for each group). Fibroblast
      proliferation was quantitated by DNA content in each culture, and collagen and
      noncollagen protein synthesis were analyzed by incorporation of [3H] proline into
      collagenase-digestible and collagenase-nondigestible protein, respectively. At
      all concentrations tested, HA significantly inhibited fetal fibroblast
      proliferation (p < 0.02), but stimulated collagen (p < 0.002) and noncollagen
      protein (p < 0.005) synthesis. These findings provide further evidence that HA
      affects the function of fetal fibroblasts. Moreover, this study in conjunction
      with previous in utero findings suggests that HA may have a regulatory influence
      in scarless fetal healing by affecting cellular function during the repair
      process.

PMID- 8309424
TI  - Dissociation of actin microfilament organization from acquisition and maintenance
      of elongated shape of human dermal fibroblasts in three-dimensional collagen gel.
AB  - Actin microfilaments of the fibroblasts cultured in a collagen gel were
      distributed along the inner surface of the entire cell membrane, in either
      spherical shape at an initial stage of culture or elongated shape at a later
      stage. The distribution was quite different from that of the fibroblast cultured
      on a two-dimensional surface, where actin microfilaments were found to be aligned
      essentially along the inner membrane which is in contact with a flat surface.
      Timing of morphological change from spherical shape to spread shape or elongated
      shape was also greatly affected by contact with substrates whether in two
      dimension or in three-dimension: distinct morphological change was observed
      within 6 h on glass or on the collagen gel, and at 30 h or later within the
      collagen gel. The retardation of cell elongation in the gel was antagonized by a
      low dose (0.2 microM) of cytochalasin D, although the drug kept the cells in
      round shape at a concentration of 2 microM. Since a low concentration of
      cytochalasin was reported to induce actin polymerization in vitro, the
      organization of actin microfilaments was examined by rhodamine-phalloidin
      staining. It was found that actin filaments in elongated cells by low
      cytochalasin D were disrupted. These results suggest that accelerated acquisition
      of elongated shape by the treatment of a low dose of cytochalasin D might be
      initiated by destabilization of the actin microfilaments that may scaffold the
      spherical shape of the cell in the collagen gel. The elongated shape thus formed
      returned to spherical upon washing of the added free cytochalasin D.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8309425
TI  - Alternate exon usage is a commonly used mechanism for increasing coding diversity
      within genes coding for extracellular matrix proteins.
AB  - Extracellular matrix proteins are a diverse family of secreted proteins and
      glycoproteins that are responsible for a variety of critical functions in
      different tissues. A large number of multiexon genes encode these proteins of the
      extracellular matrix. Over the last few years, it has become evident that the
      processing of the pre-mRNA from several of these genes involves alternative
      splicing. This review summarizes the known examples of alternative splicing in
      genes coding for the extracellular matrix and attempts to relate the increase in
      coding diversity generated by alternate exon usage to the function(s) of
      individual extracellular matrix proteins.

PMID- 8309426
TI  - Quantitative studies of human lung airspace wall in relation to collagen and
      elastin content.
AB  - Biochemical determinations of the collagen and elastin content in 50 mm3 samples
      of human lung are presented in relation to morphometric measurements of lung
      structure, as the amount of alveolar wall surface area per unit volume (AWUV), on
      adjacent slices. There were no differences in AWUV values, collagen content
      (determined as hydroxyproline) or elastin content (determined as isodesmosine)
      between upper and lower lobes within a single lung. In a study of 102 samples
      from 9 smokers lungs with no evidence of macro- or microscopic emphysema (as
      estimated by AWUV measurement), there was a negative correlation between AWUV and
      the amounts of collagen or elastin per unit volume of inflated lung. The
      correlation was stronger when collagen and elastin content were expressed per
      unit area of alveolar wall. The negative correlation is interpreted as
      representing either the anatomical variation within the complex hierarchy of
      normal lung structure or possibly low levels of fibrosis in response to cigarette
      smoking.

PMID- 8309427
TI  - Expression of the osteogenic phenotype in porous hydroxyapatite implanted
      extraskeletally in baboons.
AB  - A porous hydroxyapatite was used as a morphogenetic matrix to study early tissue
      formation preceding the morphogenesis of bone in extraskeletal sites of the
      baboon (Papio ursinus). Porous hydroxyapatites, obtained by hydrothermal
      conversion of the calcium carbonate exoskeleton of coral, were implanted
      extraskeletally in 16 baboons. Specimens were harvested at days 30, 60 and 90,
      and processed to obtain decalcified sections for histomorphometry, and
      undecalcified sections for enzyme histochemical demonstration of alkaline
      phosphatase, immunohistochemical demonstration of laminin and type I collagen,
      and for comparative histologic analysis. At day 30, the tissue that invaded the
      porous spaces showed mesenchymal condensations at the hydroxyapatite interface,
      and prominent vascular penetration. Collagen type I staining was localized within
      mesenchymal condensations. Bone had not formed in any specimen harvested at day
      30. At days 30 and 60, alkaline phosphatase staining was initially localized in
      the invading vasculature, and subsequently found in cellular condensations prior
      to their transformation into bone, and in capillaries close to cellular
      condensations. Laminin staining was localized around invading capillaries
      adjacent to and within mesenchymal condensations, and in capillaries in direct
      contact with the hydroxyapatite. Bone had formed by day 60; cartilage, however,
      was never observed. By day 90, bone formation within the porous spaces was often
      extensive. Goldner's trichrome stain and fluorescence microscopy of tetracycline
      labeled specimens demonstrated nascent mineralization within condensations during
      initial bone morphogenesis. Coating the hydroxyapatite with collagen type I
      prepared from baboon bone did not increase the amount of bone formation. In this
      hydroxyapatite-induced osteogenesis model in primates, vascular invasion and bone
      differentiation appear to be accompanied by a specific temporal sequence of
      alkaline phosphatase expression. The differentiation of osteogenic cells in
      direct apposition to the hydroxyapatite suggests that this substratum may act as
      a solid state matrix for adsorption and controlled release of endogenously
      produced bone morphogenetic proteins. The porous hydroxyapatite, as used in this
      bioassay in primates, may be an appropriate delivery system for bone
      morphogenetic proteins for the controlled initiation of therapeutic osteogenesis.

PMID- 8309428
TI  - Transient expression of type III collagen by odontoblasts: developmental changes
      in the distribution of pro-alpha 1(III) and pro-alpha 1(I) collagen mRNAs in
      dental tissues.
AB  - The expression of pro-alpha 1(III) and pro-alpha 1(I) collagen mRNAs in mouse and
      human dental tissues during tooth development and after its completion was
      analyzed by in situ hybridization, with use of [35S]-labeled RNA probes. The
      expression of pro-alpha 1(III) mRNA was also compared to that of the protein
      product, as localized by immunostaining with polyclonal antibodies to type III
      collagen and the N-terminal propeptide of type III procollagen. Contrary to many
      previous reports, our results suggest that odontoblasts express type III
      collagen. While pro-alpha 1(III) transcripts were less intensely expressed in
      odontoblasts than pro-alpha 1(I) transcripts, the amounts of both mRNAs increased
      in odontoblasts with progressing dentin formation, and decreased toward its
      completion. In contrast to pro-alpha 1(III) mRNA, pro-alpha 1(I) mRNA was still
      detectable in odontoblasts of fully developed teeth. Type III collagen
      immunoreactivity was observed in the early predentin, and again in predentin
      toward the completion of dentinogenesis, when mRNA was no longer detected. Also
      in the pulp, the protein product, unlike pro-alpha 1(III) mRNA, was relatively
      strongly expressed. Hence, these immunostaining patterns were inversely related
      to the expression of pro-alpha 1(III) mRNA, suggesting accumulation of the
      protein. The mesenchymal cells, when condensed in the region of the future
      mandibular bone, expressed pro-alpha 1(III) mRNA intensely, whereas osteoblasts
      expressed pro-alpha 1(I) but not pro-alpha 1(III) transcripts strongly. Cell type
      and developmental stage-related differences in the expression of the two mRNAs
      suggest that type I/type III collagen ratio influences the structure of dental
      tissues.

PMID- 8309429
TI  - Nationalities in Europe: the risk of war and medical responsibility.
AB  - War is often considered to be a way of solving political or economic problems. On
      the psychological level, war and acts of war are correlated with fear and guilt.
      In dealing with fear and guilt projection is a common defence mechanism, whereby
      others are scapegoated as the cause for one's own problems. This article presents
      an analysis of the relations between socio-political and economic problems, fear
      and guilt, and armed conflicts and wars. An alternative strategy is described,
      whereby people accept responsibility for the situation and work out solutions,
      based on a mature identity and by democratic processes. Conditions to promote
      this strategy are discussed. In the introduction some consequences of the last
      world war and of the work of the National Institute for the Victims of War in the
      Netherlands are described.

PMID- 8309430
TI  - MEDACT: submission of evidence, May 1993.

PMID- 8309431
TI  - William Duane and the radium cow: an American contribution to an emerging atomic
      age.
AB  - In 1912 many physicians considered radium a cure for cancer but few could afford
      it because radium cost a fortune. William Duane, Marie Curie's associate,
      discovered that "radium milk" (later officially named radon) was easier for
      physicians to use. In 1915 he built Boston's first radium "cow" and thousands of
      patients were treated with its "milk." But because radon decayed with high-energy
      alpha emissions, it also became the first "atom smasher." Making radon available
      to nuclear scientists was one of America's major contributions to an evolving
      nuclear age.

PMID- 8309432
TI  - The origins of medical physics in the USA: William Duane, Ph.D., 1913-1920.

PMID- 8309433
TI  - Application of fractal geometry techniques to the study of trabecular bone.
AB  - It is well recognized that both trabecular bone density and structure affect the
      overall bone quality and strength. In this study the aim is to quantify
      variations in the structural network of trabeculae using the concepts of fractal
      geometry. Fractal objects are objects that appear statistically similar over a
      range of scales. Typically fractals do not have smooth surfaces, but instead have
      rather complex structures with highly convoluted surfaces. Associated with every
      fractal is a characteristic dimension, called the fractal dimension. In this
      study, techniques of fractal analysis were used to characterize the trabecular
      bone matrix on digital images acquired by quantitative computed tomography (QCT)
      of dried excised human vertebral bodies (density ranging from 76-220 mg/cc) and
      photomicrography of transiliac crest biopsies. An automatic boundary tracking
      algorithm was used to identify the trabecular-bone and bone marrow interface, and
      a box-counting algorithm was used to estimate the fractal dimension of the
      trabecular boundary. Using this technique for fractal objects, if the boundary
      being analyzed is covered with boxes of differing sizes, epsilon, then the number
      of boxes N required to cover the surface increases indefinitely according to the
      relation N = epsilon-D, where D is the fractal dimension. Using this relationship
      in a preliminary study on five specimens we have found that the trabecular-bone
      boundary is fractal in nature. Using photomicrographs of iliac crest biopsies, it
      is found that the fractal dimension changes with the fractional trabecular bone
      content.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309434
TI  - Dynamic range requirements in digital mammography.
AB  - The dynamic range and the number of gray levels, gamma s, required for digital
      mammography has been evaluated using an energy transport model. The effects of
      molybdenum (Mo) and tungsten (W) target spectra and the energy-dependent
      attenuation by elemental filters, breast tissue, and a phosphor screen were
      included in the model. For detectors with ideal optical coupling and no inherent
      detector noise, 3,100 gray levels are discernable (requiring 12 bits per pixel),
      assuming a 40 kVp, W target spectrum (1.0 mm A1 filtration), a mean glandular
      dose to a 5 cm thick breast of 0.6 mGy, and an ideal observer with a 5 mm diam
      viewing aperture. The effects of inherent detector noise and realistic coupling
      efficiency on gamma s were also examined. For the 40 kVp, W spectrum, a detector
      with total coupling efficiency of 16 electrons (e-) per x-ray interaction and a
      dynamic range of 3000 (maximum carrier signal of 1.93 x 10(5) e-/pixel and
      inherent detector noise of 64 e- pixel) would decrease the number of gray levels
      that could be resolved by only 2% compared to a detector with ideal coupling and
      no inherent noise. A detector with a total coupling efficiency of 2.0 electrons
      per x-ray interaction and a dynamic range of 240 (maximum carrier signal 2.41 x
      10(4) e-/pixel and inherent detector noise of 100 e-/pixel) would reduce the
      number of gray levels by 26% for the 40 kVp spectrum. On the basis of dynamic
      range, W spectra are preferable for digital mammography, since Mo spectra
      yielding the same signal-to-noise ratio require a detector with dynamic range
      twice as large, and with a 30% greater saturation signal. When no scatter
      rejection method is used, scattered radiation over a 254 cm2 imaging field
      reduces the number of discernable gray levels by 23% for a 5 cm thick breast and
      34% for an 8 cm thick breast.

PMID- 8309435
TI  - Helical CT image noise--analytical results.
AB  - Helical CT is an important recent development in x-ray CT. In helical CT, planar
      projection sets are synthesized from raw projection data via interpolation. Among
      various interpolation schemes, linear interpolation is usually preferred due to
      its efficiency and performance. In this paper, image noise variance is derived
      for typical helical CT linear interpolation techniques, including the full scan
      (FS), under-scan (US), full scan with interpolation (FI), half-scan (HS), half
      scan with interpolation (HI) and half-scan with extrapolation (HE) methods. Image
      noise deviation ratios of helical CT to conventional 360 degrees reconstruction
      (CR) are tabulated. These are consistent with previously reported simulation
      results. The theoretical results provide further understanding of helical CT
      noise performance. It is shown that helical CT image noise deviation is
      independent of transaxial position, proportional to the raw projection noise
      deviation, and not affected by the fan angle (approximately for the HE method).
      Also, helical CT image noise variance is proportional to the area under the
      square of the reconstruction filter.

PMID- 8309436
TI  - Grooved phosphor screens for on-line portal imaging.
AB  - Video-based systems for on-line portal imaging utilize a metal plate coated with
      Gd2O2S phosphor at a typical thickness of 500 mg/cm2. A new screen design is
      proposed wherein the conventional flat phosphor coating is replaced by a much
      thicker phosphor layer (1000-2000 mg/cm2) penetrated by either lineal grooves or
      pyramidal holes comparable to the system pixel size. By increasing the surface
      area of the phosphor, the grooves or holes allow light from deep layers of the
      phosphor to escape by a process of internal reflection. In addition, the escaping
      light is strongly forward peaked, improving optical coupling to the video camera.
      The processes by which grooved screens intensify light output have been modeled
      in a simple computer program that gives approximate agreement with experiment.
      Prototype screens have been constructed that provide several times the forward
      light output of flat screens, and that improve DQE(f) in light photon limited
      systems for spatial frequencies below 0.4 mm-1.

PMID- 8309437
TI  - A modified x-ray image intensifier with continuously variable field of view:
      resolution considerations.
AB  - A conventional x-ray image intensifier (XRII) has been modified to enable the
      field of view (FOV) to be varied continuously, by adjusting the potentials at the
      focusing electrodes. The benefit, to system resolution, from decreasing the FOV
      has been characterized by measuring the modulation transfer function (MTF) of the
      XRII coupled to a high-resolution photo-diode array (PDA), at a number of
      different FOVs achieved either by electronic or optical zooming. Electronic
      zooming of the XRII from FOV = 24 cm to FOV = 10 cm led to an increase in f0.1
      (the frequency at which MTF = 0.1) from 1.41 to 3.05 mm-1, while optical zooming
      increased f0.1 from 1.41 mm-1 only to 1.88 mm-1. It is proposed that the
      advantage, with respect to resolution gain, of electronic zooming over optical
      zooming was realized only when the XRII limits system resolution. The MTF of the
      XRII coupled to a video camera, with lower resolving power than the PDA, was
      measured at different FOVs to show that using electronic zooming is only
      marginally beneficial when the optical detector and the XRII contribute equally
      to the resolution degradation. However, when a higher-resolution optical detector
      is used, electronic zooming always yields a greater gain in resolution.

PMID- 8309438
TI  - Computer-aided detection of clustered microcalcifications: an improved method for
      grouping detected signals.
AB  - A computerized scheme for the automated detection of clustered
      microcalcifications from digital mammograms is being developed. This scheme is
      one part of an overall package for computer-aided diagnosis (CAD), the purpose of
      which is to assist radiologists in detecting and diagnosing breast cancer. One
      important step in the computer detection scheme is to group or cluster
      microcalcifications, since clustered microcalcifications are more clinically
      significant than are isolated microcalcifications. Previously a "growing"
      technique in which signals (possible microcalcifications) were clustered by
      grouping those that were within some predefined distance from the center of the
      growing cluster was used. In this paper, a new technique for grouping signals,
      which consists of two steps, is introduced. First, signals that may be several
      pixels in area are reduced to single pixels by means of a recursive
      transformation. Second, the number of signals (nonzero pixels) within a small
      region, typically 3.2 x 3.2 mm, are counted. Only if three or more signals are
      present within such a region are they preserved in the output image. In this way,
      isolated signals are eliminated. Furthermore, this method can eliminate falsely
      detected clusters, which were identified by a previous detection scheme, based on
      the spatial distribution of signals within the cluster. The differences in
      performance of the CAD scheme for detecting clustered microcalcifications using
      the old and new clustering techniques was measured using 78 mammograms,
      containing 41 clusters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309440
TI  - Iterative algebraic reconstruction algorithms for emission computed tomography: a
      unified framework and its application to positron emission tomography.
AB  - In this paper, a unified framework of iterative algebraic reconstruction for
      emission computed tomography (ECT) and its application to positron emission
      tomography (PET) is presented. The unified framework is based on an algebraic
      image restoration model and contains conventional iterative algebraic
      reconstruction algorithms: ART, SIRT, Landweber iteration (LWB), the generalized
      Landweber iteration (GLWB), the steepest descent method (STP), as well as
      iterative filtered backprojection (IFBP) reconstruction algorithms: Chang's
      method, Walters' method, and a modified iterative MAP. The framework provides an
      effective tool to systematically study conventional iterative algebraic
      algorithms and IFBP algorithms. Based on this framework, conventional iterative
      algebraic algorithms and IFBP algorithms are generalized. It is shown from the
      algebraic point of view that IFBP algorithms are not only excellent methods for
      correction of attenuation (either uniform or nonuniform) but are also good
      general iterative reconstruction algorithms (they can be applied to either
      attenuated or attenuation-free projections and converge very fast). The
      convergence behavior of iterative algebraic algorithms is discussed and insight
      is drawn into the fast convergence property of IFBP algorithms. A simulated PET
      system is used to evaluate IFBP algorithms and LWB in comparison with the maximum
      likelihood estimation via expectation maximization algorithm (MLE-EM) and the
      filtered backprojection (FBP) algorithm. The simulation results indicate that for
      both attenuation-free projection and attenuated projection cases IFBP algorithms
      have a significant computational advantage over LWB and MLE-EM, and have
      performance advantages over FBP in terms of contrast recovery and/or noise-to
      signal ratios (NSRs) in regions of interest.

PMID- 8309439
TI  - Photon contribution to tumor dose from considerations of 131I radiolabeled
      antibody uptake in liver, spleen, and whole body.
AB  - The contribution of penetrating photon energy to tumor dose is usually ignored
      because of the difficulty in calculating absorbed fractions and because it is
      frequently assumed to represent a small proportion of the total energy. The
      MABDOSE software--written explicitly to simulate photon transport for the
      calculation of penetrating radiation absorbed fractions--was used to simulate the
      131I photon spectrum originating from the liver, spleen, and whole body source
      organs. Specific absorbed fractions were calculated for tumors of radius 1.0,
      1.5, and 2.0 cm placed near the liver and spleen in the Reference Man geometry.
      Cumulated activities were estimated using values reported from the literature.
      Dosimetry estimates from the combined cumulated activity and specific absorbed
      fractions indicate that neglecting the photon contribution underestimates the
      tumor dose by 10%-25%.

PMID- 8309441
TI  - Dose calculations using convolution and superposition principles: the orientation
      of dose spread kernels in divergent x-ray beams.
AB  - The convolution/superposition method of dose calculation has the potential to
      become the preferred technique for radiotherapy treatment planning. When this
      approach is used for therapeutic x-ray beams, the dose spread kernels are usually
      aligned parallel to the central axis of the incident beam. While this reduces the
      computational burden, it is more rigorous to tilt the kernel axis to align it
      with the diverging beam rays that define the incident direction of primary
      photons. We have assessed the validity of the parallel kernel approximation by
      computing dose distributions using parallel and tilted kernels for monoenergetic
      photons of 2, 6, and 10 MeV; source-to-surface distances (SSDs) of 50, 80, and
      100 cm; and for field sizes of 5 x 5, 15 x 15, and 30 x 30 cm2. Over most of the
      irradiated volume, the parallel kernel approximation yields results that differ
      from tilted kernel calculations by 3% or less for SSDs greater than 80 cm. Under
      extreme conditions of a short SSD, a large field size and high incident photon
      energy, the parallel kernel approximation results in discrepancies that may be
      clinically unacceptable. For 10-MeV photons, we have observed that the parallel
      kernel approximation can overestimate the dose by up to 4.4% of the maximum on
      the central axis for a field size of 30 x 30 cm2 applied with a SSD of 50 cm.
      Very localized dose underestimations of up to 27% of the maximum dose occurred in
      the penumbral region of a 30 x 30-cm2 field of 10-MeV photons applied with a SSD
      of 50 cm.

PMID- 8309442
TI  - Simulation of x-ray spectral reconstruction from transmission data by direct
      resolution of the numeric system AF = T.
AB  - X-ray spectral reconstruction from transmission data was investigated by direct
      resolution of the matrix system A*F = T using spectral algebra. Theoretical,
      numerical, and physical conditions were studied to obtain the physical solution
      of the problem. It is shown why the least-square-fitting methods may not give
      good results for high energy photon spectra above several MeV. The proposed
      method does not need a preshaped starting spectrum. Simulation studies have been
      made with arbitrary but realistic spectra of different shapes and maximum
      energies simulating the reality and using different materials as attenuator like
      carbon, aluminum, and even water. Conditions on the attenuator choice to obtain
      the physical solution of the system are given. The reconstruction method provides
      good results in the radiotherapy energy range despite measurement errors. The
      computation is quick and implementable on a personal computer with a mathematical
      coprocessor.

PMID- 8309443
TI  - Jaws 2: a description of in-air beam profiles for half blocked and dynamically
      wedged radiation fields.
AB  - In a recent paper [Med. Phys. 19, 1441 (1992)] it was shown that the field size
      dependence of on-axis relative output from a linear accelerator can be well
      described by a model comprising two components. One component represents
      radiation emanating from a point source and the other represents radiation from a
      field size dependent distributed source. In this communication the application of
      the model is extended to off-axis situations and demonstrates that a good
      description of the dependence of off-axis output on collimator configuration can
      be obtained. Of particular clinical relevance in this regard is the beam profile
      of half blocked fields which are adequately reproduced. The model has also been
      applied to the study of profiles generated by simulated dynamic wedging.

PMID- 8309444
TI  - Tomotherapy: a new concept for the delivery of dynamic conformal radiotherapy.
AB  - Tomotherapy, literally "slice therapy," is a proposal for the delivery of
      radiation therapy with intensity-modulated strips of radiation. The proposed
      method employs a linear accelerator, or another radiation-emitting device, which
      would be mounted on a ring gantry like a CT scanner. The patient would move
      through the bore of the gantry simultaneously with gantry rotation. The intensity
      modulation would be performed by temporally modulated multiple independent leaves
      that open and close across the slit opening. At any given time, any leaf would be
      (1) closed, covering a portion of the slit, (2) open, allowing radiation through,
      or (3) changing between these states. This method would result in the delivery of
      highly conformal radiation. Overall treatment times should be comparable with
      contemporary treatment delivery times. The ring gantry would make it convenient
      to mount a narrow multisegmented megavoltage detector system for beam
      verification and a CT scanner on the treatment unit. Such a treatment unit could
      become a powerful tool for treatment planning, conformal treatment, and
      verification using tomographic images. The physical properties of this treatment
      delivery are evaluated and the fundamental design specifications are justified.

PMID- 8309445
TI  - Electronic equilibrium and primary dose in collimated photon beams.
AB  - Electronic equilibrium conditions are studied in a homogeneous medium irradiated
      by monoenergetic photons with Compton scattering as a predominant process. Based
      on the concept of straight charged particle tracks, a geometrical model for
      spatial distribution of Compton electrons is developed in the limit of primary
      photon interactions. The model is applied to examine conditions of electronic
      equilibrium in collimated photon beams and to define equilibrium phase diagrams
      which establish correlation between various degrees of electronic equilibrium and
      primary dose. The diagrams predict that in a single direction (longitudinal or
      lateral) partial electronic equilibrium can be observed in radiation fields of
      dimensions smaller than the maximum range of secondary electrons. Associated
      macroscopic effects appear as a variation of the primary dose build-up rate with
      beam radius and depth in phantom. These effects are observed in the case of both
      primary and total absorbed dose as judged by the Monte Carlo generated data in
      waterlike material (1-8 MeV photons).

PMID- 8309446
TI  - Assessment of the accuracy of stereotactic radiosurgery using Fricke-infused gels
      and MRI.
AB  - The treatment plans for stereotactic radiosurgery employ small, circular,
      noncoplanar fields applied in a series of arcs, or with synchronous rotation of
      the accelerator gantry and patient support assembly. Primary or metastatic brain
      tumors and arterial-venous malformations are localized in relation to a
      stereotactic head frame using CT, MRI, and angiography. As x-ray doses in the
      range of 20-40 Gy are delivered in a single treatment, it is critical that the
      dose distribution produced by the accelerator accurately reflect the one
      developed by the treatment planning computer. Until the advent of Fricke-infused
      gels, whose NMR characteristics are changed by irradiation, there was no
      practical method for assessing the accuracy of x-ray beam positioning on a target
      that was localized by both CT and MRI. A stereotactic head frame was attached to
      a hollow glass head filled with a Fricke-infused gel. A 2-mm target point at
      approximately the center of this manikin was localized by CT and MRI. The head
      frame was then mounted to the patient support assembly of a linear accelerator,
      and given a dose of 40 Gy to the isocenter from 6-MV x rays using a modified
      version of the dynamic stereotactic radiosurgery plan developed in Montreal.
      Subsequent MRI showed the target point at the center of the dose distribution,
      thus confirming the accuracy of the stereotactic radiosurgery procedure. This
      demonstrated the unique characteristics of the Fricke-infused gel for the
      simultaneous localization of x-ray beams in three dimensions.

PMID- 8309447
TI  - Verification of a two-dimensional pencil beam arc electron dose calculation
      algorithm.
AB  - The dosimetry of arced electron beams is of increasing importance because of the
      increased capabilities of modern linear accelerators. A practical pencil beam
      algorithm has been developed for arc electron beams and is capable of using
      computed tomography information for heterogeneity corrections. For homogeneous
      phantoms, the maximum dose and bremsstrahlung components are predicted very
      accurately, that is, within 1% of the maximum dose. However, the depth of maximum
      dose (treatment depth) is predicted to be deeper than measurement, as much as 0.7
      cm deeper. For a heterogeneous lung phantom, the discrepancies are as high as
      30%, but the accuracy of dose calculation is consistent with conventional
      stationary pencil beam algorithms. It was concluded that improvements in the dose
      prediction are possible with more accurate calculations of the pencil beam widths
      and the incorporation of range straggling into the algorithm.

PMID- 8309448
TI  - Matching the 6-MV photon beam characteristics of two dissimilar linear
      accelerators.
AB  - A new prototype 6-MV flattening filter was designed by the manufacturer for use
      in a popular dual energy linear accelerator. To satisfy the contract demands,
      this filter was designed to produce a beam whose characteristics matched
      precisely with those of the 6-MV beam produced from a single photon peak energy
      unit from the same manufacturer and already in operation in the department. A
      single set of 6-MV dosimetric files for both units can now be maintained. The new
      filter has forced percent depth values over a wide clinical range of field sizes
      and depths to agree within 1.3%. Beam profiles now agree to within 1% over the
      useful area. For wedges with similar wedge angles, transmission factors now agree
      to within 1%. Standard acceptance testing performance specifications provided by
      the manufacturer were not adequate for clinical beam matching. The purchase
      contract for these units included our own specifications, which were more rigid
      and pertinent to our goal. Details of the effort are discussed.

PMID- 8309449
TI  - Use of a megavoltage constancy meter for orthovoltage quality assurance.
AB  - A commercial megavoltage constancy meter was tested for routine checks of the x
      ray output of an orthovoltage therapy unit. A practical method of using the meter
      for both output and energy checks was developed and is presented as part of an
      orthovoltage quality assurance program.

PMID- 8309450
TI  - The definition of transient and secular radioactive equilibrium.

PMID- 8309451
TI  - AAPM Report No. 41: remote afterloading technology.

PMID- 8309452
TI  - [The definition of research].

PMID- 8309453
TI  - [The characteristics of biomaterials: HA, titanium, polytetrafluoroethylene,
      teflon fluorocarbonate, polyglactin 910, polypropylene].

PMID- 8309454
TI  - [The physicochemical characteristics and biological profile of calcium phosphate
      bioceramics].

PMID- 8309455
TI  - [An ultrastructural morphological examination of the relationships between the
      PTFE membrane and the surrounding tissues].

PMID- 8309456
TI  - [The clinical applications of biomaterials].
AB  - The more and more availability of new alloplastic materials in oral and maxillo
      facial reconstructions causes the necessity of judging if the biomaterials
      satisfy the surgical needs. The authors re-examine the main chemical, physical
      and biological characteristics of following materials: hydroxylapatite,
      polytetrafluoroethylene, polyglactin 910, polyfluorocarbons, polypropylene and
      report their experiences.

PMID- 8309458
TI  - Brucellosis outbreak at a pork processing plant--North Carolina, 1992.

PMID- 8309457
TI  - [Clinical applications compared in implantology].
AB  - On the basis of their own experience and of orientation reported by literature,
      the authors display how important it is for professional men who practise
      implantology or who approach it, to have the possibility of knowing several
      implantologic systems. Indeed, what we want to demonstrate is, that in different
      situations of edentulous, in relation to the quantity and the quality of the
      available bones, to the gnotologic situation and to the aesthetic functional
      result they aim to, corresponds the choice of one or several implantologic
      systems. In that sense the basic research occupies a role of vital importance,
      because only through the knowledge of chemical, chemical-physical and
      biomechanical characteristics it is possible to recognize some essential chemical
      entities for an implantologic approach. Thus the several diagnostic instrumental
      means available enable the surgeon to make an exact clinical diagnosis. The TAC,
      in this case, assumes a determinant role, because, in addition to supplying exact
      dimensional and qualitative informations, also occupies an important medico-legal
      aspect. The resolution of some forms of edentulous programmed like that, will
      subsequently be illustrated. Finally, a control hypothesis is proposed for the
      rearrangement, of peri-implant bone. On this account, the SPECT (single photon
      emission computerized tomography), through a semi-quantitative research, could
      provide some specific indications about the osteotropic implantation activity.

PMID- 8309459
TI  - Daily dietary fat and total food-energy intakes--Third National Health and
      Nutrition Examination Survey, Phase 1, 1988-91.
AB  - Excessive dietary fat intake has been linked to increased risk for obesity,
      coronary heart disease, and certain cancers (1,2). The Third National Health and
      Nutrition Examination Survey (NHANES III), conducted by CDC's National Center for
      Health Statistics (NCHS), provides data to monitor changes in the dietary,
      nutritional, and health status of the U.S. population (3) and to track progress
      toward achieving the national health objectives for the year 2000, including that
      related to dietary fat intake (1). This report uses data from NHANES III, Phase 1
      (October 1988-October 1991), to present findings about daily total food-energy,
      total dietary fat, and saturated fat intakes for the U.S. population.

PMID- 8309460
TI  - Health risk behaviors among adolescents who do and do not attend school--United
      States, 1992.
AB  - High proportions of U.S. high school students engage in behaviors that place them
      at increased risk for the leading causes of death and morbidity (e.g., motor
      vehicle crashes and other unintentional injuries, homicide, suicide, heart
      disease, and cancer), unintended pregnancy, and infection with human
      immunodeficiency virus (HIV) and other sexually transmitted diseases. Because
      efforts to measure health-risk behaviors among adolescents throughout the United
      States have not included those who do not attend school, the prevalences of those
      behaviors are probably underestimated for the total adolescent population. To
      characterize more accurately the prevalence of selected health-risk behaviors
      among adolescents aged 12-19 years who do and do not attend school, CDC analyzed
      self-reported national data from the Youth Risk Behavior Survey (YRBS), conducted
      as part of the 1992 National Health Interview Survey (NHIS). This report
      summarizes the results of the analysis.

PMID- 8309461
TI  - Physical violence during the 12 months preceding childbirth--Alaska, Maine,
      Oklahoma, and West Virginia, 1990-1991.
AB  - In addition to clearly defined health risks that develop during pregnancy (e.g.,
      toxemia and diabetes), pregnant women are at risk for physical violence inflicted
      by intimate partners. Although estimates in public and private health-care
      settings indicate that 4%-17% of women experience violence during pregnancy,
      population-based prevalence estimates of this problem have not been available.
      This report uses 1990 and 1991 data from the Pregnancy Risk Assessment Monitoring
      System (PRAMS) in Alaska, Maine, Oklahoma, and West Virginia to assess the
      prevalence of physical violence against women during the 12 months preceding
      childbirth* and its relation to maternal characteristics.

PMID- 8309462
TI  - Clostridium perfringens gastroenteritis associated with corned beef served at St.
      Patrick's Day meals--Ohio and Virginia, 1993.
AB  - Clostridium perfringens is a common infectious cause of outbreaks of foodborne
      illness in the United States, especially outbreaks in which cooked beef is the
      implicated source. This report describes two outbreaks of C. perfringens
      gastroenteritis following St. Patrick's Day meals in Ohio and Virginia during
      1993.

PMID- 8309463
TI  - Progress toward elimination of Haemophilus influenzae type b disease among
      infants and children--United States, 1987-1993.
AB  - Haemophilus influenzae (Hi) causes disease among persons in all age groups, and
      Haemophilus influenzae type b (Hib) was the most common cause of bacterial
      meningitis among children in the United States. Since the introduction of Hib
      conjugate vaccines in 1988, the incidence of invasive Hib infections in the
      United States has declined among infants and children. Hib disease among children
      aged < 5 years is now included in the list of vaccine-preventable diseases
      targeted for elimination in the United States by 1996. Because Hi disease rates
      are generally higher for blacks than for whites, incidence rates are race
      adjusted; race most likely reflects differing distributions of socioeconomic risk
      factors for Hi disease (e.g., household crowding) that may account for the
      variance in incidence rates. This report summarizes race-adjusted provisional
      data about trends in invasive Hi disease from two separate surveillance systems
      and emphasizes the need for early identification, investigation, and reporting of
      Hi cases.

PMID- 8309464
TI  - NIOH and NIOSH basis for an occupational health standard: chlorobenzene.

PMID- 8309465
TI  - Clinical laboratory measurements traceable to the National Reference System for
      Cholesterol.

PMID- 8309466
TI  - [Intestinal failure--its consept, physiopathology and treatment].

PMID- 8309467
TI  - [Cryopreservation of thyroid pieces--optimal freezing condition and recovery].
AB  - We have studied the cryopreservation of thyroid pieces for the purpose of
      autotransplantation. In this paper, the optimal freezing condition was
      investigated by comparing the survival cells of the cryopreserved thyroid pieces
      under various freezing conditions, including cooling rate, freezing medium,
      cryoprotectant, size of pieces and prefreezing incubation. The recovery regarded
      as survival rate was also evaluated. Based on the results, the optimal freezing
      condition was that 1 mm 3 of the thyroid pieces in the freezing medium, consisted
      of culture medium supplemented with 10% of fetal bovine serum and 10% of
      dimethylsulfoxide, were cooled slowly until -80 degrees C with prefreezing
      incubation at 4 degrees C for 1 hour and kept in liquid nitrogen for
      preservation. The number of survival cells under the optimal condition was 1.24
      2.03 (1.71 +/- 0.40) x 10(6)/0.1 g tissue, and recovery was 25.2-58.0 (45.5 +/-
      14.6)%. This high survival rate suggests the possibility that the cryopreserved
      thyroid pieces are utilized as the autografts maintaining the intact follicles.

PMID- 8309468
TI  - [The effects of bacterial infection in bronchial stump healing and the usefulness
      of the mechanical stapling device].
AB  - It is an important problem to associate bacterial infection in the process of
      bronchial stump healing. Wound healing processes in two types of bronchial stump
      closure methods, hand suturing with absorbable threads and mechanical stapling
      with stainless steel staples, were compared in mongrel dogs (154 dogs) which
      underwent right upper lobe reactions with and without infections. Half of the
      animals were infected with 10(9) CFU/dog of Pseudomonas aeruginosa E7 organisms.
      In order to understand the influence of bacterial infection on bronchial stump
      healing and also to evaluate the usefulness of the mechanical stapling device, we
      studied the number of viable bacteria, the activities of collagenase types I, II,
      III and IV, the amount of hydroxyproline and the histopathological finding in the
      bronchial stump tissue and the maximum leakage pressure. The number of viable
      bacteria decreased daily, but more than 10(3) CFU/g were detected even on the
      21st day in infected dogs. There were no organisms detected in the stump tissues
      of uninfected dogs. The maximum leakage pressure levels by the 14th day after
      operation in the infected group were lower than in the uninfected group
      regardless of closure method. In the infected group of mechanical stapling the
      maximum leakage pressure increased daily, and on the 21st day became almost equal
      to that of uninfected group of mechanical stapling. The activity levels of
      collagenase type I in the infected group of both methods were at a maximum on the
      5th day. On the same day the amount of hydroxyproline was at a minimum, and
      maintained a low level until the 14th day.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309469
TI  - [Clinical study of the hypogastric plexus preserving operation for Y-prosthesis
      replacement for abdominal aneurysm--operative technique for avoiding
      postoperative sexual disorders].
AB  - We studied the effect of the hypogastric plexus preserving operation for Y
      prosthesis replacement in abdominal aneurysm. The hypogastric plexus preserving
      operation was performed for avoiding postoperative sexual disorders such as the
      impotence and the abnormalities of ejaculation. With wide abrasion of
      retroperitoneum as usually, postoperative abnormalities of ejaculation occurred
      in 70% and postoperative impotence occurred in 50% of cases undergoing Y
      prosthesis replacement. More reliable nerve preserving operation was the minimum
      abrasion of retroperitoneum and the aorta had not to he abrased at the origin of
      the inferior mesenteric artery, bifurcation of the aorta and the common iliac
      artery. Then with this nerve preserving operation, abnormalities of ejaculation
      occurred in 30% (p < 0.05) of cases and impotence occurred in 20% of cases. The
      results indicate that sexual dysfunction may he prevented to minimize by the
      nerve preserving operation.

PMID- 8309470
TI  - [Diagnosis of incompetent perforators in primary varicose veins by high
      resolution ultrasonography].
AB  - The purpose of this study is to investigate morphological changes of incompetent
      perforators in primary varicose vein, and to elucidate diagnostic accuracy of
      high resolution ultrasonography regarding the incompetent perforators. The
      subjects were 42 lower limbs in 28 patients. Sixteen lower limbs had stasis
      symptoms and 26 had stasis dermal findings. Perforators were diagnosed when they
      penetrated the strong echo from the fascia. Their diameter was measured and their
      subfascial draining veins were identified. By operation, their penetrating
      portions on the fascia were confirmed and bleed back test was performed. They
      were divided into 8 types according to their draining veins. Eighty-nine
      perforators were detected and of them were major 3 types. The incompetent
      perforators arose at 3mm in diameter, and the all perforators more than 7mm
      became incompetent. The diagnostic accuracy of ultrasonography regarding their
      positions was 92%. However, the diagnostic accuracy of ultrasonography regarding
      their incompetency was 65% in total accuracy, when 4mm in diameter was used as a
      cut-off line. The positions of perforators were accurately detected using
      ultrasonography, but their competency was not precisely evaluated by diameter
      measurement. Therefore, this method was available for marking the precise
      position of incompetent perforators preoperatively.

PMID- 8309471
TI  - [Two cases of thyroid cancer resected with trachea].
AB  - We described two patients of thyroid cancer with tracheal invasion. A 54-aged
      female visited our hospital with complaint of the neck pain. Echography showed a
      tumor in the right lobe of the thyroid. In operation the thyroid tumor invaded
      the trachea and right recurrent nerve. A 24-aged male visited our hospital with
      complaint of a mass of the left side neck. Echography showed a tumor in the left
      lobe of the thyroid. In operation the thyroid tumor invaded the trachea, lymph
      node and left recurrent nerve. In these two cases we could find thyroid tumors
      invaded into the trachea by echography. We re-evaluated the utility of
      echography.

PMID- 8309472
TI  - [Surgical treatment of abdominal aortic aneurysm associated with idiopathic
      thrombocytopenic purpura and consumption coagulopathy: a case report].
AB  - A 68-year-old man who had abdominal aortic aneurysm (AAA) associated with
      idiopathic thrombocytopenic purpura (ITP) and consumption coagulopathy was
      successfully operated upon. The count of platelet was improved from 1.4 x
      10(4)/microL to 8.0 x 10(4)/microL by the preoperative treatment with gamma
      globulin (400mg/kg/day for 5 days) and heparin sodium (10000-15000 unit/day).
      Abdominal aortic aneurysm was replaced with a Y-shaped knitted Dacron graft, and
      splenectomy was performed for ITP. No severe hemorrhagic diathesis was
      encountered during and after the operation. This is the first report of surgical
      treatment of AAA associated with ITP and consumption coagulopathy.

PMID- 8309473
TI  - [Experimental study on the etiology of ischemic colitis].
AB  - A reliable experimental model for ischemic colitis in rat could be obtained by
      ligating the marginal vessels of the colon 3 days after attaching the ring to
      induce partial colon obstruction. This model has the advantage of enabling to
      observe the chronic progress and the organ of the sideration to clarify the cause
      of ischemic colitis. The decrease of blood flow within the colonic mucosa
      continued up to 7 days after ligation in rat with partial obstruction, while no
      apparent abnormal changes were observed, and the previous level for several hours
      in the rats with out attaching the ring. This fact proved that the RT group is in
      a state easily developing sideration due to the sustained partial colon
      obstruction. The reactant reacting with thiobarbituric acid (TBA) was found to
      increase, in particular, 6 or more hours after ligation of vessels. A superoxide
      scavenger, liposomal-encapsulated superoxide dismutase (1-SOD) suppressed
      development of the ischemic lesion. The change in free radicals is therefore,
      considered to be involved in the occurrence of ischemic colitis.

PMID- 8309474
TI  - TCR gene segments from at least one third of V alpha subfamilies rearrange at the
      delta locus.
AB  - Using PCR and an experimentally validated V alpha subfamily-specific
      oligonucleotide panel (V alpha 1-w29), we have investigated whether the TCR delta
      chain may increase its combinatorial diversity by using V genes considered as
      alpha chain-specific. We show that at least 10 distinct human V alpha segments
      rearrange at the J delta locus, leading to scrambling of the two V gene
      repertoires. Fifty-five per cent of the V alpha/J delta transcripts characterized
      here were in frame. The 17 V alpha/C delta chains analysed included an extended
      CDR3 region with up to 18 aa encoded by the junctional region. In addition, a new
      J delta segment (J delta 4) has been characterized. Together, these findings
      demonstrate that combinatorial diversity in the human delta locus is larger than
      previously thought.

PMID- 8309475
TI  - Expression of immunoglobulin heavy chain-ricin A chain fusions in mammalian
      cells.
AB  - Mammalian cell lines were transfected with antibody heavy (H) chain-ricin A chain
      gene fusions in attempts to assemble a recombinant immunotoxin. We found that a
      light chain-secreting mouse plasmacytoma cell line can be transfected stably with
      such a chimaeric gene, but only if the ricin A chain portion is disarmed by
      genetic means prior to transfection; if not, stable transfection appears to
      select for genetic inactivation of the transfected gene. Co-expression of an
      antibody heavy chain-ricin A chain fusion with light chain in non-lymphoid cells
      results in cell death. We conclude that the ricin A chain moiety retains
      biological activity precluding the expression of biologically active antibody
      ricin A chain fusion proteins in mammalian cells.

PMID- 8309476
TI  - Differences in the biochemical properties of esterolytic antibodies correlate
      with structural diversity.
AB  - A prerequisite to the design and engineering of catalytic antibodies is the
      knowledge of their structure and in particular which residues are involved in
      binding and catalysis. We compared the structure and catalytic properties of a
      series of six monoclonal antibodies which were all raised against a p-nitrophenyl
      (PNP) phosphonate and which catalyze the hydrolysis of p-nitrophenyl esters.
      Three of the antibodies (Group I) have similar light and heavy chain variable
      regions. The other three antibodies have similar VL regions of which two (Group
      II) have VH regions from the MOPC21 gene family and the remaining one (Group III)
      a VH from the MC101 gene family making a total of three different groups based on
      their V region sequences. The structural division into groups is paralleled by
      the differences in binding constants to hapten analogs, substrate specificity and
      the susceptibility of the catalytic activity of the antibodies to chemical
      modification of tryptophan and arginine residues. The relative binding of a
      transition state analog to the binding of substrate is much higher for the Group
      I antibodies than for the other groups. Only the Group I antibodies can catalyze
      the hydrolysis of a carbonate substrate. However all of the antibodies lose
      catalytic activity upon specific tyrosine modification which highlights the
      importance of tyrosine in the active site of the antibodies. Thus, antibodies
      raised against a single hapten can give antibodies with different structures, and
      correspondingly different specificities and catalytic properties.

PMID- 8309477
TI  - An upstream protein interacts with a distinct protein that binds to the cap site
      of the human interleukin 1 beta gene.
AB  - Interleukin 1 beta (IL-1 beta) is a proinflammatory cytokine that exhibits a wide
      variety of biological activities. Genomic sequences that mediate the induction of
      human IL-1 beta gene transcription by lipopolysaccharide and phorbol esters are
      located more than 2,700 bp upstream of the transcriptional start site (cap site).
      These upstream elements require additional cap site-proximal (CSP) sequences
      which are necessary for basal transcription of the human IL-1 beta gene. In
      addition, these CSP sequences have been shown to mediate both cell type-specific
      expression of this gene, and trans-activation by some viral proteins. In this
      study, we report the identification of a novel nuclear protein, termed NF beta C,
      that binds to a DNA sequence which spans the cap site of the human IL-1 beta gene
      (positions -12 to +8). We have also identified a second region (positions -305 to
      -280) containing a putative NF-kappa B binding site. We show here that this
      region can bind three distinct nuclear proteins. One protein is similar or
      identical to NF-kappa B, a second protein (termed NF beta B) binds a distinct
      sequence that substantially overlaps the 5' half of the NF kappa B binding
      sequence, and a third protein (termed NF beta D) binds a distinct sequence that
      substantially overlaps the 3' half of the NF kappa B binding sequence. Unlike NF
      kappa B, NF1 beta B and NF beta D are present in nuclear extracts prepared from
      unstimulated monocytic cells. Although the NF beta D and NF beta C binding
      sequences share no significant similarity, each sequence can specifically compete
      for the binding of either protein to DNA, whereas oligonucleotides containing
      only the NF kappa B or NF beta B motifs do not compete for the binding of NF beta
      C or NF beta D. This suggests that NF beta C and NF beta D can specifically
      interact in vitro, possibly through a common subunit.

PMID- 8309478
TI  - Characterization of monoclonal anti-furosemide antibodies and molecular modeling
      studies of cross-reactive compounds.
AB  - Four mouse monoclonal antibodies directed against furosemide have been isolated
      and characterized. The cross-reactivity of the antibodies with eight compounds
      which are structurally and/or functionally related to furosemide was determined
      using a competition ELISA. All of the compounds, including furosemide, were then
      modeled using molecular mechanical and quantum mechanical methods in an attempt
      to correlate antibody binding with the conformational and electronic properties
      of the molecules. The results of these experiments demonstrated that all of the
      cross-reactivity observed could be readily explained using these techniques.
      Furthermore, these results should allow for more accurate prediction of
      unexpected cross-reactivities with these antibodies when they are used in
      immunoassays for determination of furosemide.

PMID- 8309479
TI  - Expression and purification of biologically active domain I of the human
      polymeric immunoglobulin receptor.
AB  - Previous studies using proteolytic fragments and synthetic peptides have
      indicated that domain I of human polymeric immunoglobulin receptor (PIgR) is
      necessary for ligand binding. The expression in E. coli, and subsequent IgM
      affinity purification of domain I of human PIgR is described. The recombinant
      domain I protein (rDI) was similar in structure to native SC domain I in that it
      bound specifically to MAb 6G11, an antibody which recognizes a critical portion
      of the PIg binding site in domain I. The biological activity of rDI was indicated
      by high affinity binding to PIgA (Kd = 1.6 x 10(-7) M) and IgM (Kd = 5.1 x 10(-7)
      M). Domain I of human SC is therefore sufficient for binding to PIg.

PMID- 8309480
TI  - Mapping the upstream boundary of somatic mutations in rearranged immunoglobulin
      transgenes and endogenous genes.
AB  - Mammalian B-cell specific somatic hypermutation contributes to affinity
      maturation of the antibody response. This mutator activity is highly focused on
      rearranged immunoglobulin variable regions, but the underlying mechanism remains
      to be elucidated. In an effort to gain insights into the mechanism of somatic
      hypermutation, the precise distribution and frequency of mutations upstream of
      murine immunoglobulin genes was determined by examining the same variable gene
      segments when mutated in different B-cell lines. Immunoglobulin sequences
      analysed included kappa light chain transgenes bearing mutated V kappa 24
      variable regions, and the endogenous V kappa gene isolated from myeloma MOPC167,
      which also exhibits mutations in the variable region. In addition, mutated
      endogenous VH1 gene segments of the S107 heavy chain variable gene family were
      also examined. For both VH1 and V kappa 24, somatic mutations were generally not
      found upstream of the leader intron, even in genes which exhibited a high
      mutation frequency in the variable region itself. The 5' somatic mutation
      boundary identified in immunoglobulin transgenes overlaps the boundary observed
      in endogenous genes, suggesting that both share cis-elements required for
      defining the mutable domain. Furthermore, the location of this 5' boundary
      appears not to change when these immunoglobulin genes are examined in different
      cell lines. These data may be indicative of a defined start site for
      immunoglobulin mutator activity.

PMID- 8309482
TI  - German Society for Pharmacology and Toxicology. 5th winter meeting. Hannover,
      Germany, 1-3 December 1993. Abstracts.

PMID- 8309481
TI  - Intron sequences determine the expression of kappa light chain genes.
AB  - Alterations in kappa light chain expression were demonstrated to originate from
      genomic changes in the L-V intron (L-IVS) which changed the splicing pattern of
      the kappa mRNA. In R15, a mutant of mouse myeloma W3129 which produces no kappa
      light chain, a 358 bp novel sequence element (R15ns) of unknown origin replaced
      19 bases of wild-type L-IVS, both altering the normal splicing pattern and
      activating a cryptic polyadenylation site. Subclones of R15 which reverted to
      kappa light chain production contained genomic deletions of R15ns and/or the
      surrounding intron. These deletions led to partial or full restoration of wild
      type kappa mRNA levels due to further changes in the pattern of mRNA processing.
      Two cryptic splice acceptor sites and a polyadenylation signal exist in the L
      IVS; a cryptic splice acceptor sequence also exists in V kappa. These cryptic
      sites can be activated by changing the genomic context. It is thus possible to
      influence light chain expression without altering either the exon sequences or
      the known regulatory elements. Alterations in splicing patterns also serve to
      produce kappa light chains with novel variable region sequences and thereby could
      contribute to antibody diversity. Surprisingly, in the cell line producing this
      novel kappa light chain, intact alpha heavy chains were secreted in the absence
      of an apparent association with light chain. These studies also demonstrate that
      it is not possible to distinguish functional from non-functional genes solely by
      sequence analysis and that genes can both be inactivated and activated by changes
      in intron sequences.

PMID- 8309483
TI  - A descent into the maelstrom.

PMID- 8309484
TI  - Clinton health system reform.

PMID- 8309485
TI  - Hyperglycemia as a paraneoplastic endocrinopathy in renal cell carcinoma: a case
      report and review of the literature.
AB  - A case of renal cell carcinoma presenting with severe hyperglycemia,
      ketoacidosis, and hyperosmolar coma is described. Hyperglycemia was difficult to
      control but improved dramatically after nephrectomy and required no further
      insulin therapy. Hyperglycemia as a paraneoplastic endocrinopathy in renal cell
      carcinoma is suggested.

PMID- 8309486
TI  - Vaginal birth after cesarean section in a rural private setting.

PMID- 8309487
TI  - Time to think.

PMID- 8309488
TI  - What physicians need to know about the Nebraska Workers Compensation Law.

PMID- 8309489
TI  - Microvascular reconstruction of the head and neck cancer patient.
AB  - Surgical resection of cancer of the head and neck often results in significant
      functional and cosmetic deformity. Reconstruction of these deficits have often
      been inadequate to reintegrate these patients into daily life. Recent advances in
      microsurgical techniques, however, have ushered in a new era for reconstruction
      following head and neck cancer ablative surgery. Microvascular free tissue
      transfers have made possible the reconstruction of major head and neck defects
      that previously were not possible as well as markedly improving function and
      cosmesis. Successful reconstruction requires close cooperation between the head
      and neck ablative surgeon as well as the reconstructive surgeon. We describe four
      different microvascular flap techniques which we have used for head and neck
      cancer reconstruction to illustrate some of the many applications of these
      microvascular flaps.

PMID- 8309490
TI  - Stereotactic breast biopsy: initial experience and recommendations for
      improvement.
AB  - The results of 54 stereotactic core breast biopsies performed at Bishop Clarkson
      Memorial Hospital were reviewed. In 47 biopsies (87% of the total), a definitive
      diagnosis of either benign or malignant was made. Two biopsies (4% of the total)
      were classified as missed, and 5 biopsies (9% of the total) were deemed
      indeterminate. To improve both the success of the procedure and patient
      management, six recommendations were made: Patients judged to be potentially
      uncooperative and inclined to move during the procedure should receive sedation.
      A post-biopsy, non-stereo film should be taken to determine whether additional
      stereotactic biopsies will be required to adequately sample the lesion. Lesions
      containing microcalcifications should have a specimen radiograph prior to
      completing the biopsy procedure. A history sheet including clinical and
      mammographic findings should be given to pathology along with the biopsy specimen
      to assist in the histologic interpretation. The radiologist should review the
      pathology results in order to determine if a miss has occurred and additional
      biopsy is indicated. Six-month follow-up mammograms are to be required following
      a benign stereotactic biopsy diagnosis.

PMID- 8309491
TI  - Newborn eye prophylaxis--where are we now?

PMID- 8309492
TI  - [Relative postnatal growth of the basal regions of the cranial fossa].
AB  - The relative postnatal growth of the bony floor parts was calculated from
      previous measurements and planimetrically determined on 21 adults and 13 skulls
      of children. As expected 1) the percentage rise in length and breadth values was
      lower than that of the area values. 2) The greatest postnatal area rise (63%) was
      determined in the hypophyseal region. 3) The growth of the individual skull areas
      terminates at a variable period after birth, e.g. a) between the foramen caecum
      and the tuberculum sellae in the 8th year of life; the planum sphenoidale,
      however, grows after the 9th year of life by approx. 27%! b) In children of 8
      years of age, the lateral length of the middle cranial fossa is about 98% of the
      adult value. c) Between the 6th year of life and adult age a length increase of
      18.5% takes place (tuberculum sellae--dorsum sellae). d) In 5-year old children
      the lateral length of the posterior cranial fossa is 97.5%, in 8-year-olds 99.9%
      of the adult value. e) After the 8th year of life the breadth increase is e.g.
      6.4% in the region of the anterior cranial fossa, 3.5% in the middle fossa, and
      10% in the pituitary region.

PMID- 8309493
TI  - A trans-orofacial approach for the removal of an extracranial meningioma in the
      skull base.
AB  - Two rare cases of extracranial meningiomas associated with intracranial masses
      are reported. From the roentgenological findings both of the tumors were regarded
      as being partly connected. The tumors were surgically treated 21 and 19 years,
      respectively, after the first removal of the intracranial masses. They appeared
      as nasal-oral and orbicular masses, respectively, and were histologically
      diagnosed as meningotheliomatous meningioma. In one case a partial removal of a
      naso-oral tumor, including a subtotal removal of the tumor in the lateral orbital
      cavity, was performed by Weber-Kocher's incision plus Kronlein's incision. In the
      other case a tumor was removed via a transoral route by a lateral retraction of
      one half of the mandible after cutting it into halves. Our operative approaches
      and origins of the tumor are discussed.

PMID- 8309494
TI  - [Supratentorial glioma: analysis of clinical and temporal parameters in 163
      cases].
AB  - 163 cases of supratentorial astrocytomas and glioblastomas were evaluated
      retrospectively after close-meshed observation and treatment. We attached the
      greatest importance to the reevaluation of already known prognostic parameters
      and to the temporal analysis of the course of gliomas. We could confirm the
      influence of the histologic grade on the survival time. Histologic grading by
      means of immunohistochemistry proved to be more precise than grading only by
      means of HE staining. Furthermore, the patient's age was one of the most
      important prognostic variables for survival time after operation. Other factors
      were the first preoperative Karnofsky rating, the preoperative diameter of the
      tumour, the duration of preoperative symptoms and the interval between operation
      and diagnosis of tumour recurrence as well as between tumour recurrence and
      reoperation. Epileptic seizures as preoperative symptoms were found to be far
      less prognostic for survival time. Localisation of the tumour, other preoperative
      symptoms, Karnofsky rating before reoperation and the extent of tumour resection
      proved to be of no importance for survival time.

PMID- 8309495
TI  - [Clinical aspects and pathology of intracranial subependymoma--18 personal cases
      and review of the literature].
AB  - Intracranial subependymomas are rare, benign tumours (WHO grade I) occupying a
      special position compared to the other ependymal neoplasms. They often remain
      asymptomatic and, in consequence, are found incidentally at autopsy. In the
      present study clinico-pathological data of 84 symptomatic (8 own cases) and 58
      asymptomatic tumours (10 own cases) are summarised. Subependymomas are more
      frequently situated in the fourth (58.4%) than in the lateral ventricle (38.0%).
      They occur predominantly in middle-aged and elderly males. Tumours in the lateral
      ventricles manifest themselves more often than those in the fourth ventricle. In
      general, asymptomatic subependymomas do not exceed a diameter of 1.2 cm. The
      nature of symptoms, with a median symptomatic period of 12 months, is usually
      associated with hydrocephalus, which is present in more than 80% of the symptom
      producing subependymomas. Growth within the ventricular lumen and sharp
      demarcation from the surrounding brain tissue allow a complete removal in half of
      the cases. Radical extirpation can be achieved more often in patients with
      subependymomas located in the lateral ventricles than in those with tumours
      arising from the floor of the fourth ventricle. The high operative mortality, at
      a rate of 28.8% so far, mainly refers to the period before microsurgical
      technique was established. Recurrences are very rare, spinal seeding has not been
      found to date. For the assessment of long-term results further detailed
      compilation and documentation of individual follow-ups is necessary.

PMID- 8309496
TI  - Tumors of the nasal cavity occurring after hypophysectomy.
AB  - Olfactory neuroblastoma and malignant melanoma of the nasal cavities as second
      primary tumors after resection of pituitary adenomas in two patients are
      described. These cases, which seem to be the first documented in the literature,
      demonstrate the problems in diagnosis and treatment. Because of its rare
      occurrence, a second primary tumor may not be suspected when symptoms develop in
      the region of a previous hypophysectomy. A close follow-up after hypophysectomy
      for pituitary adenoma is recommended for the early detection of a second primary
      tumor. Pathogenetic considerations are discussed.

PMID- 8309497
TI  - [Spinal seeding metastasis of a WHO grade III oligo-astrocytoma].
AB  - 3 1/2 years after two operations and radiation therapy of a biparietally,
      parasagittaly localised grade III oligoastrocytoma, a 34-year-old patient
      developed symptoms of the spinal cord. By performing magnetic resonance
      tomography and laminectomy, multiple metastases of the anaplastic part of the
      primary tumour could be identified. Spinal seedings of a tumour of this grading
      are even rarer than those sporadically reported on corresponding complications of
      a multiform glioblastoma. Risk factors for the development of such a complication
      are youth of the patient, primary site of the tumour near the midline and
      anaplastic parts of the tumour in adults. If such a constellation exists, one
      should definitely consider the possibility of a spinal seeding in a grade III
      glioma, especially because in these younger patients thus would be of greater
      relevance for therapy than in patients with multiform glioblastoma.

PMID- 8309498
TI  - [Primary leptomeningeal sarcomatosis in a 26-year-old patient].
AB  - Primary malignant mesenchymal tumours were seen in 2.4 per cent of all autopsy
      cases with primary CNS-tumours. Primary leptomeningeal sarcomatosis is rare in
      this group of tumours. We discuss the rare disease on the basis of the case
      history of a 26-year-old patient.

PMID- 8309499
TI  - Gangliosides and Guillain-Barre syndrome: the Spanish data.
AB  - Although ganglioside administration has been suspected as being responsible for
      Guillain-Barre syndrome (GBS) and peripheral neuropathies in some patients,
      current epidemiological, experimental, and clinical data do not support such an
      association. In Spain, a total of 17 cases of suspected GBS and neuropathy had
      been reported to the National Drug Surveillance System as of April 15, 1992. No
      definite relationship between ganglioside administration and the illness in these
      cases could be established after careful review of available data.

PMID- 8309501
TI  - Epidemiology of neuromuscular diseases, including the postpolio sequelae, in a
      Swedish county.
AB  - The epidemiology of neuromuscular diseases was studied in the county of Orebro,
      Sweden (study population 270,000). Several different sources of data were
      utilized, compared and validated. On the prevalence of day (January 1, 1988) 474
      patients were identified. The rate per 100,000 population was 92 for the
      postpolio sequelae (PPS) and 84 for the other neuromuscular diseases (motor
      neuron disease 9, hereditary neuropathies 9, myoneural disorders 16, myotonic
      disorders 19, muscular dystrophies 20 and myositis 11). Of the patients with the
      PPS, 80% reported late-onset symptoms. On the basis of an expanded survey
      including all medical records in one health care district, the prevalence of the
      PPS was estimated to be 186/100,000 population.

PMID- 8309500
TI  - Generalized neuropathy in Taiwan: an etiologic survey.
AB  - From July 1988 to June 1989, the etiology was registered of 520 patients with
      generalized neuropathy in 5 neurological centers in Taiwan. The neuropathy was
      diabetic in 256 cases (49.23%), alcoholic in 45 (8.65%), inflammatory in 34
      (6.53%; including 21 with acute inflammatory demyelinating polyneuropathy, 12
      with chronic inflammatory demyelinating polyneuropathy, and 1 with chronic
      relapsing polyneuropathy), 12 with associated malignancy (2.31%), 9 with
      dysproteinemia (1.73%), uremic in 22 (4.23%), hereditary motor and sensory in 22
      (4.23%), toxic in 14 (2.69%), ischemic in 12 (2.31%), hypothyroidism in 10
      (1.92%), nutritional deficiency and malabsorption in 6 (1.15%), chronic liver
      disease in 4 (0.77%), other diseases in 11 (2.12%) and unclassified in 63
      (12.12%). This survey provided a crude etiological picture of generalized
      neuropathy on this island.

PMID- 8309502
TI  - Primary tumors of the brain, cranial nerves and cranial meninges in Victoria,
      Australia, 1982-1990: patterns of incidence and survival.
AB  - This report presents for the first time a detailed analysis of the distribution
      of primary brain tumors in a population in Australia. Data on 3,575 cases of
      benign and malignant tumors of the brain, cranial nerves and cranial meninges
      diagnosed among residents of the state of Victoria from 1982 to 1990 are used to
      calculate incidence rates and survival by histologic type, age and sex and to
      compare incidence of birthplace, socioeconomic status and year of diagnosis. No
      sharp decline in incidence rates is seen among those over age 60 and only small
      increases in incidence over the 9-year period have been observed. The overall
      incidence rates, distributions by histologic type, and patterns of excess
      incidence among those born in Southern and Eastern Europe and the Middle East are
      similar to observations in other geographic areas. No clear trend relating
      incidence and socioeconomic status is observed. Survival after brain tumor
      diagnosis is better among women then men (52 vs. 37% survive 5 years); this
      difference is attributable to the greater frequency among men of the more
      aggressive tumor types. The most striking male over female excess is for
      medulloblastoma, a type that occurs predominantly in the pediatric age group.
      This excess coupled with the fact that this tumor occurs at a much younger age in
      males may suggest the presence of a genetic predisposition in some patients with
      this disease.

PMID- 8309503
TI  - Anticoagulation for atrial fibrillation and stroke prevention.
AB  - Nonvalvular atrial fibrillation (NVAF) has a prevalence of about 1% in the 60- to
      70-year age group, increasing to above 4% in persons older than 80 years. The
      yearly stroke incidence in NVAF patients is 3-8%, which is 5-7 times higher than
      that in age-matched persons in sinus rhythm. In five independent studies of
      stroke prevention in NVAF patients, anticoagulation therapy resulted in a risk
      reduction of stroke of about 65%. The risk of intracerebral hemorrhage was 0.3%
      per year during warfarin therapy compared with 0.1% in the placebo group. In one
      study aspirin reduced the risk of thromboembolic events by 42% while another
      study found a nonsignificant effect of aspirin. The following variables were
      identified as risk factors for stroke in the individual studies: prior myocardial
      infarction, increasing age, mitral annular calcification, history of
      hypertension, congestive heart failure and previous arterial thromboembolism. A
      pooled analysis of risk factors in the placebo-treated patients of the five
      studies is ongoing.

PMID- 8309505
TI  - Motor neuron disease on the Kii Peninsula of Japan: cycad exposure.
AB  - In the Hohara area of Nansei-cho, one of the foci of motor neuron disease (MND)
      on the Kii Peninsula, an inquiry was conducted to investigate whether cycad
      exposure is an etiological factor of MND in the western Pacific. Although cycads
      were commonly used as medicine around World War II all over Japan, the medicinal
      use of cycads was exceptional in the Hohara area. A questionnaire study in the
      Hohara and the neighboring four areas in Nansei-cho showed that cycad used as
      food, medicine, toys, and garden trees had no relation to the incidence of MND in
      these areas. The result in the Hohara area does not support the hypothesis that
      cycad is an etiological factor of MND common to the western Pacific foci.

PMID- 8309504
TI  - Prevalence study of neurologic disorders in Kelibia (Tunisia).
AB  - A full-scale survey, in Kelibia, Tunisia, screening 34,874 persons started on
      July 1, 1985. The accuracy of this survey was evaluated by a second survey using
      a randomized sample of 1,673 subjects (control survey). Better selection and
      training of the interviewers during the control survey led to a higher positive
      predictive value with no modification in prevalence ratios of neurologic
      disorders. The control survey helped to validate the full-scale survey data which
      were then used to establish the prevalence ratios of major neurologic disorders
      in Kelibia. Prevalence ratios, age-adjusted to the WHO population, were compared
      to those of studies using similar methodology. Migraine prevalence ratios in
      Nigeria, Ecuador, and Kelibia were equivalent. Epilepsy and Parkinson's disease
      prevalence ratios were close to those of other similar studies. The stroke
      prevalence ratio was low, compared to other studies, but was not the lowest. It
      seems that in Kelibia, stroke does not constitute a public health problem as it
      does in the USA or urban China. The large full-scale survey, in Kelibia, provided
      estimates of prevalence ratios for stroke, epilepsy, migraine and other common
      neurologic disorders for comparisons with other countries. However, definitions
      of neurologic disorders and diagnostic criteria differ from one study to another
      making difficult the comparison of results between different countries. Had the
      WHO protocol developed well-defined criteria and a standardized neurologic
      examining tool, more accurate comparisons could have been made.

PMID- 8309506
TI  - Incidence and risk factors for Bell's palsy in Laredo, Texas: 1974-1982.
AB  - Incidence rates of Bell's palsy in the predominantly Mexican-American population
      of Laredo, Texas, USA, are higher than those reported elsewhere, reaching 23.5
      per 100,000 among males and 32.7 per 100,000 among females. During childbearing
      years (15-44) the risk of Bell's palsy was greater for women than for men
      (incidence density ratio 2.0; 95% confidence interval 1.3-3.1). No evidence for
      seasonality or epidemicity was obtained. Using prevalence estimates from
      community surveys in south Texas or the Hispanic Health and Nutrition Survey,
      standardized prevalence ratios (SPR) calculated for hypertension revealed a 10 or
      20% increased risk for women and a 50 or 60% increased risk for men. SPRs
      calculated for diabetes among men with Bell's palsy were twice that expected,
      while risks of 60% or 90% were noted for women. The increased incidence of Bell's
      palsy observed in Laredo appears to be due to the high prevalence of diabetes in
      Mexican-Americans and, to a lesser extent, uncontrolled hypertension.

PMID- 8309507
TI  - Reappraisal of the incidence rate of Duchenne and Becker muscular dystrophies on
      the basis of molecular diagnosis.
AB  - The incidence rates of Duchenne and Becker muscular dystrophies (X-linked
      recessive) in a given sample of the Italian population were recalculated using
      the results of DNA and dystrophin analysis. While the incidence rate of Duchenne
      muscular dystrophy remained unchanged, the new figure for the incidence of Becker
      muscular dystrophy (7.2 per 100,000 male live births) was much higher than
      previously reported, since molecular diagnosis revealed additional cryptic cases,
      but this incidence is still an underestimate.

PMID- 8309508
TI  - Juvenile lower cervical spinal muscular atrophy in Taiwan: report of 27 Chinese
      cases.
AB  - Clinical observations as well as electromyographic studies were carried out on 27
      Taiwanese Chinese patients deemed to be suffering from a rare, unique and self
      limiting variant of lower motor neuron disease affecting the upper limbs with
      juvenile onset and a marked male preponderance. The results agree with previous
      descriptions of the disease except for the higher incidence of triceps affection.
      The term 'juvenile lower cervical spinal muscular atrophy', which describes the
      disease more accurately, is being proposed. The geographic relevance is
      discussed.

PMID- 8309509
TI  - Parkinson's and Alzheimer's diseases: epidemiological comparison. 1. Descriptive
      aspects.
AB  - Parkinson's (PD) and Alzheimer's (AD) diseases are age-related degenerative
      disorders that share common clinical, pathological and biochemical features.
      Epidemiological studies show similar age-specific incidence and prevalence
      curves, although PD tends to occur at earlier ages and, at old age, AD is more
      frequent. Both diseases are more common in western than in Mediterranean or
      Asiatic populations. These findings suggest that these diseases may have common
      determinants.

PMID- 8309510
TI  - Parkinson's and Alzheimer's diseases: epidemiological comparison. 2. Persons at
      risk.
AB  - Parkinson's and Alzheimer's diseases are age-related degenerative disorders that
      share common clinical, pathological and biochemical features. Epidemiological
      studies demonstrate a similar distribution of the disease in place and time.
      Causes of death and populations at higher risk are similar. These findings
      suggest that these diseases must have common determinants.

PMID- 8309511
TI  - Glucose-6-phosphate dehydrogenase deficiency and multiple sclerosis in northern
      Sardinia.

PMID- 8309512
TI  - Diffuse white matter disease in three children: an encephalopathy with unique
      features on magnetic resonance imaging and proton magnetic resonance
      spectroscopy.
AB  - Amongst 21 children with unclassified white matter diseases three patients could
      be characterised by an identical clinical picture, magnetic resonance imaging
      (MRI) and proton magnetic resonance spectroscopy (MRS) findings as a probably
      distinct entity. Following a normal early development they later showed rapidly
      progressive motor symptoms (ataxia, spasticity) leading to severe handicap within
      one or two years after onset. Later on bulbar symptoms, optic atrophy and
      epileptic seizures occurred. The MRI showed a diffuse homogeneous hypodensity of
      the white matter almost identical to the signal of the ventricles. MRS revealed a
      near total absence of N-acetylaspartate, choline and creatine and an increase of
      lactate and glucose. One girl and one boy were siblings, indicating an autosomal
      recessive trait.

PMID- 8309513
TI  - Photosensitivity--genetics and clinical significance.
AB  - Photosensitivity is defined by the occurrence of spikes or spikes and waves in
      response to intermittent light stimulation (= photoparoxysmal response [PPR]).
      The EEG pattern can show a wide range of expression from solely occipital spikes
      to generalized irregular spikes and waves. The different types of responses
      represent different levels of expression of the same genetically determined
      trait. The photoconvulsive response of Bickford et al (7) is only a subtype of
      the PPR characterized by close relation to epilepsy. The average incidence of PPR
      is 7.6% in healthy children aged 1 to 16 years. Girls are more often affected
      than boys. The available data provide evidence for autosomal dominant inheritance
      of photosensitivity. Genetic heterogeneity must be considered. In studies
      starting from a neurobiological genetic point of view including the whole
      spectrum of PPR, the phenomenon could be shown to be a widespread condition being
      only loosely associated with epilepsy, but more often with symptoms of
      psychovegetative instability. Only about 3% of children with PPR of the given
      definition will manifest epilepsy up to age 20 years. According to family studies
      in epileptic and non-epileptic photosensitive probands, the phenotypical
      expression of the PPR and carriers' risk to manifest epileptic phenomena is
      decisively determined by other pathogenetic factors related to epilepsy. Possible
      interactions of photosensitivity within the multifactorial pathogenetic
      background of the epilepsies are reviewed.

PMID- 8309514
TI  - Cerebral magnetic resonance imaging (MRI) and mental and motor function of very
      low birth weight infants at one year of corrected age.
AB  - Thirty-one (77.5%) of a year cohort of 40 surviving infants with birth weight <
      1500 grams were seen on follow-up examination at one year of corrected age. At
      neurological evaluation 20 infants were normal (Group 1), seven infants were
      considered at risk (Group 2), and four infants had cerebral palsy (Group 3).
      Assessment on the Bayley Scales gave significantly lower mean scores in Group 3
      compared with Group 1, both on the Mental Index (63 versus 102, p < 0.001) and on
      the Psychomotor Index (PDI) (60 versus 94, p < 0.005). Mean PDI score in Group 2
      was significantly lower than in Group 1 (74 versus 94, p < 0.005). Cerebral MRI
      was performed in 27 infants. Of the 19 infants in Group 1 examined with MRI, 14
      infants showed deviating changes in both myelin deposition and maturation (2). In
      all 14 infants the central occipital white matter was affected and in three
      infants also the centrum semiovale, both areas correspond to predilection sites
      for periventricular leukomalacia (PVL). Five infants had irregular shape of the
      occipital horns of the lateral ventricles. These findings may also represent the
      end stages of PVL (4). Only four out of seven infants were examined with MRI in
      Group 2. However, three infants had deviating myelination and three had irregular
      shape of the posterior horns. In Group 3 all infants were examined with MRI and
      all had deviating myelination and irregular and slightly dilated posterior horn.
      There was a significant correlation between abnormally dilated occipital horns
      seen with MRI, and cerebral palsy and low scores on the Denver and the Bayley
      tests.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309515
TI  - Correlation between the degree of periventricular leukomalacia diagnosed using
      cranial ultrasound and MRI later in infancy in children with cerebral palsy.
AB  - During a period of 30 months, 504 infants of 34 weeks gestation or less were
      enrolled in a prospective cranial ultrasound study. Ninety-two (18.4%) infants
      developed different degrees of periventricular leukomalacia (PVL), being
      transient periventricular echogenicities (PVE) in 75, localised cystic lesions in
      7 and extensive cysts in 10. Eight of 75 (10.6%) infants with PVE, 4 of the 6
      (66.6%) survivors with localised cysts and all 8 survivors with extensive cysts
      developed cerebral palsy in infancy and MRI studies could be performed in 15 of
      these 20 infants between 11 and 32 months of age. Neurological sequelae were most
      severe among the infants with extensive cysts and none were able to walk, while 6
      of the 12 who developed cerebral palsy following either PVE or localised cysts
      had learned to walk independently. There appeared to be a good correlation
      between the degree of PVL, diagnosed using ultrasound, and the extent of MRI
      changes noted in infancy. Ventricular enlargement and delay in myelination were
      more common in infants with cystic lesions and periventricular hyperintensity
      (PVHI) was present in all infants, but most extensive in the cases with extensive
      cysts. MRI performed later in infancy may, even in the absence of neonatal
      cranial ultrasound, provide information about both the presence as well as the
      degree of leukomalacia, which the child may have suffered in the neonatal or
      antenatal period.

PMID- 8309516
TI  - Outcome of transient periventricular echodensities in preterm infants.
AB  - In this prospective study routine ultrasound scanning of the brain was performed
      in all 353 infants of less than 32 weeks of gestation who had been admitted to
      our neonatal intensive care unit from 1987-1990. Ten infants (2.8%) showed
      transient periventricular echodensities (TPE) without the subsequent development
      of cysts and/or ventricular dilation. Nineteen infants (5.4%) developed
      periventricular leukomalacia (PVL). At the corrected age of 2 years the
      neurodevelopmental outcome was assessed. Five children with PVL had died before
      the age of 2 years. The neurodevelopmental outcome of children with TPE and PVL
      was compared with the outcome of 21 preterm children matched for gestational age,
      birth weight and severity of illness, and without ultrasound abnormalities of the
      brain in the neonatal period, who had also been admitted to our neonatal
      intensive care unit during the study period. Children with TPE and PVL appeared
      to have more handicaps than the control children. The children with TPE had
      significantly more minor motor handicaps than the control children, while the
      children with PVL had more major handicaps of all origins. Although infants with
      TPE had a more favorable prognosis than infants with PVL they should not be
      disregarded because TPE appear to be of clinical importance.

PMID- 8309517
TI  - Infantile spasms: infectious disorders.
AB  - Infections were considered to be etiological factors in 29 patients (10%) with
      infantile spasms; congenital CMV (n = 5), congenital or acquired CMV (n = 1),
      acquired CMV (n = 5), congenital rubella (n = 2), herpes simplex virus (n = 5),
      enterovirus (n = 1), adenovirus (n = 1), viral encephalitis of unknown agent (n =
      3), meningococcus (n = 4), pneumococcus (n = 1) and pertussis (n = 1). The
      children with congenital infections had long-lasting tremor and convulsions from
      birth. Early EEG pattern was characteristic for children with herpes encephalitis
      but not for other patients. Infantile spasms appeared only some weeks after viral
      encephalitis. One patient with enterovirus and another with probable adenovirus
      infection had necrotic changes in their brain CT resembling those of herpes
      encephalitis. The response to ACTH was poor (38%) compared to the whole series
      (60%). The long-term outcome was also poor compared to the whole series; mental
      retardation in 90%, convulsions in 62%, abnormal EEG in 89%. Four children died
      during the follow-up of 7 years. Autopsy showed disseminated CMV infection in one
      patient and chronic CMV infection in another. The outcome of children with
      infectious etiology appears to be particularly poor. Thus, the prevention and
      specific diagnosis and treatment are important. Steroid therapy should be avoided
      in children with a history of herpes virus encephalitis (CMV, herpes simplex) in
      the past.

PMID- 8309518
TI  - Effects of long barbiturate anaesthesia on eight children with severe epilepsy.
AB  - Frequent epileptic seizures in children are often related to delayed psychomotor
      development, and status epilepticus is always a neurological emergency. In both
      situations barbiturate anaesthesia has been used for status epilepticus since the
      1960s, and for intractable seizures in children since the 1980s. However, the
      clinical results on the effectiveness of barbiturate anaesthesia in children with
      chronic epileptic disorders remain contradictory. Between 1986 and 1991 in
      Tampere University Hospital in Finland long barbiturate anaesthesia was
      introduced--using thiopentone sodium--to eight children with very severe
      epilepsy. Children were 10 months to 7 years 11 months of age and the mean time
      from the onset of seizures to the introduction of BA was 2 years 8 months.
      Effects upon seizure frequency, antiepileptic medication and/or psychomotor
      development were clearly positive in three patients, slightly positive in one
      patient and in four patients there was no effect. Good effect seemed to be
      associated with an anaesthesia which is deep and long enough to produce loss of
      consciousness and spontaneous reactions, and an electroencephalographic pattern
      of burst-suppression. Positive results were also more often achieved when the
      treatment lag was less than 12 months. Physical and neurophysiological properties
      of barbiturates make their effectiveness as anticonvulsants understandable, but
      there is only little evidence to explain the mechanism of this action.

PMID- 8309519
TI  - Subtotal aplasia of myelinated nerve fibers in the sural nerve.
AB  - Thus far, only very few cases with neuronal maldevelopment in the peripheral
      nervous system have been reported (Table 1). The present sporadic case manifested
      itself with peripheral sensorimotor polyneuropathy in early infancy. Clinical
      findings included pareses and hypaesthesia of distal extremities and severely
      reduced nerve conduction velocities. During adolescence, cerebellar ataxia
      developed. Sural nerve biopsy taken at the age of 14.5 years showed severe
      fascicular hypoplasia, aplasia of large myelinated nerve fibers, and subtotal
      deficiency of small myelinated nerve fibers without numerical reduction of
      unmyelinated axons. There was no structural evidence of a progression of
      myelinated fiber breakdown although some collagen pockets and empty Schwann cell
      processes among preserved unmyelinated axons indicated some loss of unmyelinated
      fibers. These findings are interpreted as representing maldevelopment of the
      myelinated fibers in the peripheral nervous system. Appropriate classification of
      this unique disease among the known developmental disorders of peripheral nerves
      is discussed.

PMID- 8309520
TI  - Clinical features of Kleine-Levin syndrome with localized encephalitis.
AB  - We report the clinico-pathological findings regarding a 9 year-old girl with some
      clinical features of Kleine-Levin syndrome who died suddently as a result of
      pulmonary embolism in the course of femoro-iliac thrombophlebitis.
      Neuropathological examination provided evidence of perivascular inflammatory
      infiltrates and microglial proliferation of nodular type located in the
      diencephalon and midbrain. These findings suggest that a localized encephalitis
      may be the underlying condition in Kleine-Levin syndrome.

PMID- 8309521
TI  - Activity-dependent neuronal-glial and synaptic plasticity in the adult mammalian
      hypothalamus.

PMID- 8309522
TI  - Oxytocin binding sites in rat limbic and hypothalamic structures: site-specific
      modulation by adrenal and gonadal steroids.
AB  - Basal density and estrogen induction of oxytocin binding sites in limbic and
      hypothalamic structures of the rat brain were investigated by semi-quantitative
      autoradiography following chronic administration of dexamethasone or
      progesterone. The selective oxytocin receptor antagonist
      d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)] ornithine-vasotocin was used as a ligand for
      oxytocin binding sites. Estrogen administration increased ligand binding in all
      sites investigated. Dexamethasone treatment significantly increased ligand
      binding in the bed nucleus of the stria terminalis, lateral ventral septum and
      amygdala to an extent which was comparable to that of estradiol alone. In the
      hypothalamic ventromedial nucleus, dexamethasone significantly decreased basal
      levels of oxytocin binding. Estrogen administration subsequent to dexamethasone
      failed to cause a further increase in oxytocin binding in all structures
      investigated. Chronic progesterone treatment significantly increased basal
      oxytocin receptor density in the limbic structures, decreased it in the
      ventromedial nucleus, and prevented estrogen-induced increases in ligand binding
      in all areas studied with the exception of the medial preoptic area. These
      findings demonstrate that, in addition to gonadal steroids, glucocorticoids
      differentially and site-specifically modulate cerebral oxytocin binding sites.
      The evidence for glucocorticoid and gestagen influences on oxytocin receptors and
      their inducibility by estrogen may be relevant to the understanding of mechanisms
      leading to impairment of oxytocin-related behaviours.

PMID- 8309523
TI  - Alterations of the GluR-B AMPA receptor subunit flip/flop expression in kainate
      induced epilepsy and ischemia.
AB  - In the hippocampus, glutamatergic pathways are altered following seizure activity
      or transient global ischemia, both pathological conditions leading to selective
      neuronal degeneration. Glutamatergic receptors, and notably alpha-amino-3-hydroxy
      5-methyl-4-isoxazolopropionate (AMPA) receptors, a family of glutamate receptors
      involved in fast synaptic transmission and in the maintenance of synaptic
      potentiation may play an important role in the pathological outcome. AMPA
      receptors are assembled from GluR-A, GluR-B, GluR-C and GluR-D polypeptides which
      exist in flop and flip variants, the latter allowing larger glutamate responses.
      Using in situ hybridization techniques, we show that kainate-induced epilepsy
      provokes a rapid but transient increase (50%) of GluR-B flip mRNA levels in all
      subregions of the hippocampus (CA1, CA3, dentate gyrus). This early phase is
      followed by a second, persistent GluR-B flip increase in regions in which neurons
      are known to be seizure-resistant (i.e. CA1 an dentate gyrus) while a 35%
      decrease is observed in the vulnerable CA3 area. Following global ischemia, the
      levels of GluR-B flip and flop variants are dramatically reduced (90-100%), well
      before any morphological signs of cell death, in the subiculum and CA1, two areas
      known to be particularly sensitive to ischemic insult. In keeping with the
      properties of GluR flip variants, it is suggested that altered subunit
      stoichiometry may lead to long-lasting enhanced efficiency of fast synaptic
      transmission in the epileptic hippocampus. Since GluR-B containing receptors are
      Ca2+ impermeable, our results also suggest altered Ca2+ permeability in the
      vulnerable pyramidal neurons of areas CA3 and CA1 in the epileptic and ischemic
      hippocampi, respectively.

PMID- 8309524
TI  - The behavior of mossy cells of the rat dentate gyrus during theta oscillations in
      vivo.
AB  - Intracellular current clamp recordings were obtained from mossy cells (n = 6,
      identified by intracellular injection of biocytin) of the dorsal dentate gyrus
      from rats under ketamine-xylazine anesthesia. During electroencephalographic
      theta rhythm (4-6 Hz), recorded with a macroelectrode placed in the contralateral
      dorsal hippocampus near the fissure, mossy cells displayed intracellular membrane
      potential oscillations at low frequencies (4-6 Hz) which appeared to be phase
      locked to the electroencephalographic theta rhythm. The frequency of the
      intracellular theta rhythm was independent of the membrane potential. However,
      the phase difference between the intracellular and the electroencephalographic
      theta rhythms as well as the amplitude of the intracellular theta oscillations
      were voltage-dependent. These findings are consistent with the hypothesis that
      rhythmic GABAA receptor-mediated inhibitory postsynaptic potentials contribute to
      the genesis of the intracellular theta rhythm. Indeed, mossy cells displayed an
      early, fast inhibitory postsynaptic potential in response to electrical
      stimulation of the entorhinal cortex, which most likely represents a GABAA
      receptor-mediated event, indicating that mossy cells possess functional GABAA
      receptors. At the resting membrane potential, mossy cells did not fire at each
      cycle of the electroencephalographic theta rhythm but fired only rarely (< 1 Hz).
      However, when they did fire they did so preferentially in phase with the peak
      positivity of the electroencephalographic theta rhythm. Reconstruction of two
      mossy cells with axonal projections to the inner molecular layer showed that the
      spatial extent of the influence such weakly discharging mossy cells may have on
      other dentate gyrus neurons during theta oscillations can be several millimeters
      in the septotemporal direction. In conclusion, these findings show that mossy
      cells of the rat hilus during ketamine-xylazine anesthesia participate in theta
      oscillations of the hippocampal formation, during which their low-frequency
      firing may contribute to the phase-locking of a large number of spatially
      distributed postsynaptic neurons with postsynaptic sites in the inner molecular
      layer of the dentate gyrus.

PMID- 8309525
TI  - Disinhibition of hippocampal CA3 neurons induced by suppression of an adenosine
      A1 receptor-mediated inhibitory tonus: pre- and postsynaptic components.
AB  - Intracellular recordings were performed on hippocampal CA3 neurons in vitro to
      investigate the inhibitory tonus generated by endogenously produced adenosine in
      this brain region. Bath application of the highly selective adenosine A1 receptor
      antagonist 1,3-dipropyl-8-cyclopentylxanthine at concentrations up to 100 nM
      induced both spontaneous and stimulus-evoked epileptiform burst discharges. Once
      induced, the 1,3-dipropyl-8-cyclopentylxanthine-evoked epileptiform activity was
      apparently irreversible even after prolonged superfusion with drug-free solution.
      The blockade of glutamatergic excitatory synaptic transmission by preincubation
      of the slices with the amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM), but not with the N
      methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovaleric acid (50
      microM), prevented the induction of epileptiform activity by 1,3-dipropyl-8
      cyclopentylxanthine. The generation of the burst discharges was independent of
      the membrane potential, and the amplitude of the slow component of the paroxysmal
      depolarization shift increased with hyperpolarization, indicating that the 1,3
      dipropyl-8-cyclopentylxanthine-induced bursts were synaptically mediated events.
      Recordings from tetrodotoxin-treated CA3 neurons revealed a strong postsynaptic
      component of endogenous adenosinergic inhibition. Both 1,3-dipropyl-8
      cyclopentylxanthine and the adenosine-degrading enzyme adenosine deaminase
      produced an apparently irreversible depolarization of the membrane potential by
      about 20 mV. Sometimes, this depolarization attained the threshold for the
      generation of putative calcium spikes, but no potential changes resembling
      paroxysmal depolarization shift-like events were observed. At the concentrations
      used in electrophysiological experiments (30-100 nM), 1,3-dipropyl-8
      cyclopentylxanthine displayed only a negligible inhibitory action on total cyclic
      nucleotide phosphodiesterase activity measured by means of a radiochemical assay
      in a homogenate of the rat cerebral cortex. Furthermore, even high concentrations
      of the selective phosphodiesterase inhibitor rolipram (10 microM), which displays
      no affinity to adenosine receptors, did not mimic the electrophysiological
      actions of 1,3-dipropyl-8-cyclopentylxanthine, thus excluding the possibility
      that the effects of the A1 receptor antagonist on neuronal discharge behavior can
      be ascribed to an inhibition of phosphodiesterases. The present data demonstrate
      that endogenously released adenosine exerts a vigorous control on the
      excitability of hippocampal CA3 neurons on both the pre- and postsynaptic sites.
      The long-lasting disinhibition following a transient suppression of adenosinergic
      inhibition strongly suggests that, besides its well-known short-term effects on
      neuronal activity, adenosine might also contribute to the long-term control of
      hippocampal excitability.

PMID- 8309526
TI  - Patch-clamp recording from Muller (glial) cell endfeet in the intact isolated
      retina and acutely isolated Muller cells of mouse and guinea-pig.
AB  - Muller cells span through the entire retina and terminate with the formation of
      endfeet at the vitreous body. These endfeet are thought to be specialized for
      maintaining the K+ homeostasis in the retina based on the assumption that voltage
      signals can passively spread from the cell body to the endfeet. We employed the
      patch-clamp technique to study the physiological properties of these endfeet in a
      retinal wholemount preparation from guinea-pig or mouse. After assessing one
      endfoot with the patch pipette and establishing the whole cell recording
      configuration, a membrane area which approximately matched the size of one
      endfoot and proximal process could be voltage-clamped. This morphological
      correlation could be established by filling the cytoplasm with the fluorescent
      dye Lucifer Yellow via the patch-pipette. The morphological, immunocytochemical
      and ultrastructural inspection of the recorded cells revealed that mouse Muller
      cell endfeet were connected by only a thin stalk to the proximal process. In
      contrast, guinea-pig endfeet were connected by thick stalks. The endfoot current
      in the mouse was dominated by a voltage and time-independent K+ conductance. In
      contrast, in some of the recordings from guinea-pig, delayed and inwardly
      rectifying K+ currents were observed. These voltage-gated currents were more
      frequently observed or were facilitated when the membrane area under voltage
      clamp was increased, blocking the passive K+ currents by Ba2+ in both, mouse and
      guinea-pig. We thus assume that the voltage-gated currents were not in the
      endfeet membrane, but rather in the proximal process and could thus be better
      activated in the guinea-pig with its thicker stalk or after increasing the
      membrane area under voltage clamp control. Similar results were obtained in
      freshly isolated Muller cells; in contrast to the cells from the wholemount the
      voltage-gated currents were more frequently observed. These studies demonstrate
      that the Muller cell endfoot of the mouse with its vascularized retina is an
      electrically isolated unit and that voltage signals do not spread to the proximal
      process. Such a property would, however, be required for the redistribution of K+
      via spatial buffer currents. In contrast, guinea-pig Muller glial cells with
      their stout morphological connection between endfoot and proximal process are
      better suited to fulfil this task.

PMID- 8309527
TI  - Expression of acetylcholinesterase messenger RNA in human brain: an in situ
      hybridization study.
AB  - The distribution of messenger RNA coding for acetylcholinesterase was studied in
      human post mortem brain and rhesus monkey by in situ hybridization histochemistry
      and compared to the distribution of acetylcholinesterase activity.
      Acetylcholinesterase messenger RNA had--similar to acetylcholinesterase enzymatic
      activity--a widespread distribution in human bain. Acetylcholinesterase messenger
      RNA positive cells corresponded to perikarya rich in acetylcholinesterase
      activity in most but not all regions. Examples for mismatches included the
      inferior olive and human cerebellar cortex. The presence of hybridization signals
      in cerebral cortex and an enrichment in layer III and V of most isocortical areas
      confirmed that perikaryal acetylcholinesterase in cerebral cortex is of
      postsynaptic origin and not derived from cholinergic projections. In striatum the
      expression of high levels of acetylcholinesterase messenger RNA was restricted to
      a small population of large striatal neurons. In addition, low levels of
      expression were found in most medium sized striatal neurons. Cholinergic neurons
      tended to express high levels of acetylcholinesterase messenger RNA whereas in
      cholinoceptive neurons the levels were moderate to low. However, some
      noncholinergic neurons like dopaminergic cells in substantia nigra, noradrenergic
      cells in locus coeruleus, serotoninergic cells in raphe dorsalis, GABAergic cells
      in thalamic reticular nucleus, granular cells in cerebellar cortex and pontine
      relay neurons expressed levels comparable to cholinergic neurons in basal
      forebrain. It is suggested that neurons expressing high levels of
      acetylcholinesterase messenger RNA may synthesize acetylcholinesterase for axonal
      transport whereas neurons with an expression of acetylcholinesterase confined to
      somatodendritic regions tend to contain lower levels of acetylcholinesterase
      messenger RNA.

PMID- 8309528
TI  - Subsets of neurotensin-immunoreactive neurons in the rat striatal complex
      following antagonism of the dopamine D2 receptor: an immunohistochemical double
      labeling study using antibodies against Fos.
AB  - A study was done to determine if the Fos and neurotensin immunoreactivities
      elicited in the rat striatal complex by the selective dopamine D2 receptor
      antagonist, S(-)-eticlopride hydrochloride are co-localized in the same neurons.
      Following injections of eticlopride, Fos and neurotensin immunoreactivity were
      both non-uniformly distributed among the striatal compartments and
      subterritories. Fos was co-localized in a significant number of small, lightly
      neurotensin-immunoreactive neurons, but not in a larger subset of neurons with
      significantly greater median diameter that exhibited intense neurotensin
      immunoreactivity extending well into the dendritic arbor. It is proposed that
      neurotensin-immunoreactive neurons lacking Fos immunoreactivity are prominent
      following selective blockade of the dopamine D2 receptor and represent a subset
      of striatal neurotensin-immunoreactive neurons. Neurotensin-immunoreactive cells
      containing Fos nuclei represent a distinct subset, possibly the one that is
      dominant following administration of reserpine [Zahm (1992) Neuroscience 46, 335
      350]. Insofar as Fos expression has been reported to accompany activation of
      striatonigral and striatopallidal neurons, the absence of Fos in the subset of
      neurotensin neurons displayed following D2 receptor blockade may be at odds with
      activation and perhaps is more consistent with inactivation and accompanying
      decreased release of neurotensin [see Frey et al. (1988) Neurochem. Int. 12, 33
      38, and Bean et al. (1989) J. Neurosci. 9, 4430-4438] as a mechanism underlying
      the accumulation of neurotensin in that subset of striatal neurons.

PMID- 8309530
TI  - Chronic continuous and intermittent L-3,4-dihydroxyphenylalanine treatments
      differentially affect basal ganglia function in 6-hydroxydopamine lesioned rats-
      an autoradiographic study using [3H]flunitrazepam.
AB  - The effects of chronic 'continuous' and 'intermittent' L-3,4
      dihydroxyphenylalanine treatments on GABA receptor function in the basal ganglia
      of rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle
      was investigated, by autoradiography with [3H]flunitrazepam. The 6
      hydroxydopamine lesion itself, increased [3H]flunitrazepam binding in the
      substantia nigra pars reticulata (+17%, with respect to intact side) and
      entopeduncular nucleus (+44%), but decreased binding in the globus pallidus of
      the denervated hemisphere (-20%). 'Intermittent' L-3,4-dihydroxyphenylalanine
      treatment reduced the [3H]flunitrazepam binding changes observed in the
      substantia nigra pars reticulata (-13%) and entopeduncular nucleus (-4%), whereas
      'continuous' infusion of the same daily dose of L-3,4-dihydroxyphenylalanine had
      less effect (+14%, substantia nigra pars reticulata; +26%, entopeduncular
      nucleus). In contrast, the [3H]flunitrazepam binding decrease in the globus
      pallidus of the 6-hydroxydopamine lesioned animals was unaffected by either
      regime of chronic L-3,4-dihydroxyphenylalanine treatment. The changes in GABA
      receptor function implied by these results provide further insight into the
      pathophysiological effects of L-3,4-dihydroxyphenylalanine treatment on basal
      ganglia function, following dopamine denervation. In accordance with existing
      electrophysiological and biochemical evidence on this subject, the main
      implications of these results include reduced GABA sensitivity of neurons in the
      entopeduncular nucleus and substantia nigra pars reticulata, following chronic
      'intermittent', but not chronic 'continuous' L-3,4-dihydroxyphenylalanine
      treatment; this may be due to a reversal of the 6-hydroxydopamine induced
      decrease in the GABA-mediated neurotransmission in the striatoentopeduncular and
      striatonigral pathways. In contrast, the regulation of GABA receptors in the
      globus pallidus does not appear to be subject to modulation by chronic L-3,4
      dihydroxyphenylalanine administration, suggesting that dopamine replacement in
      this manner does not modify the 6-hydroxydopamine induced increase in GABA
      mediated neurotransmission in the stratopallidal pathway.

PMID- 8309529
TI  - Spatial organization of patch and matrix compartments in the rat striatum.
AB  - The visualization of mu opiate receptors by [3H]naloxone binding was used to
      determine precisely the spatial organization of the patch compartment in the rat
      striatum and its reproducibility in different animals. Three-dimensional
      reconstruction of the patch network was made using maps of autoradiographic data
      obtained from successive coronal, sagittal or horizontal sections. The extreme
      rostral pole of the striatum (A 11) was characterized by a large patch territory
      exhibiting complex and tortuous fields with several extensions. In the
      intermediate part of the structure (A 9.0-10.0), about 20 serial parallel
      continuous patch channels running in a mediolateral axis, obliquely oriented and
      displaying in some cases connecting branches, could be observed. However, no
      channels could be distinguished in the rostrocaudal direction. More caudally,
      patches were rare and of small size. In addition, the laterocaudal region of the
      striatum was almost exclusively represented by a large matrix field. Finally, a
      fine discontinuous band of [3H]naloxone binding was seen in all sections,
      bordering and limiting the dorsolateral part of the striatum. The topographical
      and spatial distribution of the patch compartment was similar in all animals
      investigated. However, due to the tortuous shape and the labyrinthine
      organization of the patches, the precise degree of reproducibility from one
      animal to another could not be established. Nevertheless, the prominent patch
      compartment observed in the rostral pole of the striatum, the patch channels,
      oriented in the mediolateral axis as well as the large laterocaudal matrix field
      were observed in all cases. These results were compared with previous data
      obtained in the cat in which patch (striosome) channels oriented along a
      rostrocaudal axis are also observed.

PMID- 8309531
TI  - Topographical organization of the sources of discrete cortical projections within
      the striatum as determined by a retrograde fluorescence tracing technique in the
      cat.
AB  - The projections from the neostriatum and the paleostriatum to the cerebral cortex
      in the cat were examined by means of retrogradely transported fluorescent tracers
      primuline, Fast Blue, Nuclear Yellow and Evans Blue injected into different
      neocortical fields. In all cases after dye injections only large labelled cells
      of sources of striatocortical ipsilateral projections were observed. The main
      projections from the caudate nucleus and the putamen are directed to the auditory
      and neighbouring "associative" cortex, and more numerous projections from the
      globus pallidus are addressed to the motor cortex. No sources of cortical
      projections within the entopeduncular nucleus were found. Simultaneous injections
      of Fast Blue and primuline into even closely located and tightly bound functional
      regions of parietal or temporal cortex failed to reveal double-labelled neurons
      in the caudate nucleus, internal capsule, putamen and globus pallidus. Thus, our
      findings on cats are consistent with recent studies on rats and monkeys that
      suggest that striatal neurons innervate relatively small, restricted fields of
      the neocortex. Again, the results show evidence for a significant contribution to
      cholinergic cortical innervation not only of magnocellular neurons of the basal
      forebrain but also of large neo- and paleostriatal cells.

PMID- 8309532
TI  - Corticoamygdaloid and corticocortical projections of the rat temporal cortex: a
      Phaseolus vulgaris leucoagglutinin study.
AB  - The projections of the rat temporal cortex to the amygdala and cerebral cortex
      were studied using the sensitive anterograde tracer, Phaseolus vulgaris
      leucoagglutinin. These studies revealed that the core of temporal area 1 had no
      projections to the amygdala but did send efferents to several cortical fields
      that projected to the amygdala, including temporal area 2, temporal area 3, the
      lateral occipital area 2, and a cortical zone along the dorsal, rostral and
      caudal borders of temporal area 1 ("Tel fringe"). The temporal area 1 fringe
      cortex had light projections to the amygdala that were confined to the
      dorsolateral subdivision of the lateral amygdaloid nucleus. Temporal area 2 and
      the caudal portion of temporal area 3 had projections to both the dorsolateral
      and ventromedial subdivisions of the lateral nucleus; the projection from
      temporal area 2 targeted mainly the ventromedial subdivision, whereas the
      projection from the caudal portion of temporal area 3 terminated primarily in the
      dorsolateral subdivision. The rostral portion of temporal area 3 had projections
      to both subdivisions of the lateral nucleus and to the basal magnocellular
      nucleus. Temporal areas 2 and 3 also had light projections to the lateral
      capsular subdivision of the central amygdaloid nucleus. Temporal cortical areas
      exhibited extensive reciprocal connections with each other. Temporal areas with
      amygdaloid projections also had extensive projections to the perirhinal cortex.
      The results of the present investigation, in conjunction with other studies of
      temporal cortical connections, suggest that all temporal regions projecting to
      the amygdala are multimodal sensory areas. The core of temporal area 1, which is
      probably the primary auditory area, apparently has no direct projections to the
      amygdala. The differential projections of different temporal areas to the
      amygdala suggests the existence of several distinct multimodal pathways arranged
      in a parallel configuration.

PMID- 8309533
TI  - Effects of lesions in the horizontal diagonal band nucleus on olfactory
      habituation in the rat.
AB  - The nucleus of the horizontal limb of the diagonal band, a component of the basal
      forebrain magnocellular complex affected in Alzheimer type dementia, supplies
      centrifugal innervation to the olfactory bulb. We have tested the hypothesis that
      horizontal limb of the diagonal band lesions will interfere with olfactory memory
      in a simple olfactory test paradigm. Lesions occupied a restricted volume,
      approximately 20%, of medial horizontal limb of the diagonal band. There was
      interference with habituation of investigation latency and duration, six and 16
      days after lesioning. It is concluded that bilateral partial lesions of the
      medial nucleus of the horizontal limb of the diagonal band interfere with
      habituation memory for odours.

PMID- 8309534
TI  - Characterization of resiniferatoxin binding sites on sensory neurons: co
      regulation of resiniferatoxin binding and capsaicin sensitivity in adult rat
      dorsal root ganglia.
AB  - Binding of [3H]resiniferatoxin was seen by autoradiography in sections of rat
      dorsal root ganglia and the superficial dorsal horn of the spinal cord. Membranes
      from rat dorsal root ganglia and spinal cord, but not other tissues, had
      saturable high-affinity binding sites for [3H]resiniferatoxin. A series of
      capsaicin analogues competed for these sites. The sites probably correspond to
      capsaicin receptors. Systemic pretreatment of rats with capsaicin caused loss of
      capsaicin sensitivity in sensory neurons and a reduction in binding of
      resiniferatoxin to rat dorsal root ganglia, measured by binding assays and
      autoradiography. Adult rat dorsal root ganglion neurons cultured without nerve
      growth factor also lost their capsaicin-sensitivity and showed reduced
      resiniferatoxin binding. Therefore, capsaicin responses in sensory neurons may be
      regulated by nerve growth factor through control of the number of capsaicin
      receptors.

PMID- 8309535
TI  - GAP 43-like immunoreactivity in normal adult rat sciatic nerve, spinal cord, and
      motoneurons: axonal transport and effect of spinal cord transection.
AB  - Using immunofluorescence and cytofluorimetric scanning techniques in the rat, the
      fast anterograde and retrograde axonal transport of growth-associated protein-43
      like immunoreactivity in normal sciatic nerves, and after spinal cord transection
      in the lower thoracic region, were investigated. Spinal roots and motor endplates
      in the peroneal muscles were also studied. For comparison, anti-synaptophysin
      (p38) was used. In intact adult animals, the amounts of immunoreactive growth
      associated protein-43 increased linearly, both proximally and distally to the
      crush site, between 1 and 24 h after crushing the sciatic nerve. The
      accumulations were present in thick as well as in thin axons. Distal
      accumulations in the sciatic nerve were about 40-60% of the proximal amounts,
      indicating a recycling of organelles with growth-associated protein-43-like
      immunoreactivity. During the week after spinal cord transection, no clear changes
      were observed; the anterograde transport of growth-associated protein-43-like
      immunoreactivity showed a tendency to decrease at day 1 and then a tendency to
      increase, reaching 120% of control at seven days (not significant). Transported
      p38-like immunoreactivity showed similar but smaller changes. In the lumbar
      spinal cord gray matter many nerve terminals with growth-associated protein-43
      like immunoreactivity were seen in intact animals. After spinal transection,
      these terminals gradually decreased, suggesting that they belonged to descending
      pathways. However, p38-positive terminals were not obviously decreased. After
      crushing ventral and dorsal roots, accumulations of pf growth-associated protein
      43-like immunoreactivity were present in thick axons in the ventral roots and in
      thin to medium-sized axons in the dorsal roots. In peroneal muscles, growth
      associated protein-43-like immunoreactivity was present in some (but not all)
      motor endplates in all groups. These results indicate that: (i) growth-associated
      protein-43 is normally present in nerve terminals of many descending projections
      of the spinal cord; (ii) growth-associated protein-43-like immunoreactivity is
      expressed and bidirectionally transported in neurons (motor as well as sensory)
      of normal sciatic nerves; (iii) growth-associated protein-43-like
      immunoreactivity is present in some adult motor endplates; and (iv) inhibited
      supraspinal input causes minor, if any, alterations--paralleled by p38--in axonal
      transport of growth-associated protein-43-like immunoreactivity.

PMID- 8309537
TI  - Functional nicotinic receptor expression in mesodermal cells transfected with
      MyoD cDNA.
AB  - Previous studies had shown that MyoD promoted nicotinic acetylcholine subunit
      gene expression; the present experiments were done to determine whether this
      subsequently led to the development of functional nicotinic acetylcholine
      receptors. Transfection of C3H 10T1/2 cells with MyoD cDNA resulted in the
      appearance of [125I]alpha-bungarotoxin binding sites; radiolabelled alpha-toxin
      binding was not observed in cells transfected with a plasmid that lacked MyoD
      cDNA. Receptor development plateaued over a time course of several days with
      maximal binding seven and 11 days after exposure to fusion medium. [125I]alpha
      bungarotoxin binding was of high affinity (Kd = 1 nM), saturable and was
      inhibited by nicotinic but not muscarinic receptor ligands, with IC50s of 1-3 nM
      for alpha-bungarotoxin, 1-3 microM for d-tubocurarine and 3-10 microM for
      nicotine. Not only did the cells exhibit a cell surface nicotinic receptor but
      they also expressed a nicotinic receptor mediated functional response. Carbachol
      resulted in uptake of 22Na into the cells at concentrations similar to those
      required for receptor activation at a muscle type nicotinic receptor;
      furthermore, the functional response was effectively blocked by nicotinic
      receptor ligands, including alpha-bungarotoxin (IC50 = 2 to 6 nM) and d
      tubocurarine (IC50 = 0.1 to 0.4 microM); muscarinic receptor ligands had no
      effect. A time course study showed that alpha-bungarotoxin binding and carbachol
      stimulated 22Na uptake developed in parallel, suggesting that the observed
      functional response was mediated through an interaction at the alpha-bungarotoxin
      recognition site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309536
TI  - Ontogeny of diazepam-binding inhibitor-related peptides (endozepines) in the rat
      brain.
AB  - Benzodiazepine receptors are expressed very early in the brain during embryonic
      life, suggesting that endogenous ligands for these receptors may play an
      important role during ontogenesis in the central nervous system. In the present
      study, the distribution and characterization of diazepam-binding inhibitor
      related peptides (endozepines) in the rat brain was investigated during embryonic
      and postnatal development using an antibody raised against the biologically
      active region of the precursor molecule. Immunohistochemical labelling showed
      that, in newborn rats, endozepine-like immunoreactivity was present in ependymal
      cells of the hypothalamus. Although the number of positive cells increased by day
      5, the intensity of the immunoreaction in each cell diminished. In 15-day-old
      rats, both the number of endozepine positive cells and the intensity of the
      immunoreaction increased in the ependymal layer. At day 40, a dense accumulation
      of immunoreactive tanycytes and glial cells was observed in the median eminence
      and the arcuate nucleus. Endozepines were detected by radioimmunoassay in all
      regions of the brain as early as embryonic day 18. The concentration of
      endozepine-related peptides increased in the hypothalamus and olfactory bulb
      during late gestation. Between birth and postnatal day 5, the levels of
      endozepines decreased two- to four-fold in all brain regions studied. Thereafter,
      endozepine concentration increased gradually until day 25. Reversed-phase high
      performance liquid chromatography analysis of tissue extracts revealed that the
      olfactory bulb, pituitary, hypothalamus and cerebellum contained only one
      immunoreactive peak eluting at 39 min (peak C). In the telencephalon two peaks
      were observed: peak C and a second one eluting at 34 min (peak B). Peak B was
      present as early as embryonic day 20 and the ratio peak B/peak C gradually
      increased until day 25. At day 25 peak B was also detected in hippocampus,
      medulla oblongata, cortex and striatum extracts. In any brain region, no
      immunoreactivity co-eluting with the octadecaneuropeptide was observed. Sephadex
      G-50 gel filtration of hypothalamus extracts of 25-day-old animals, confirmed the
      existence of only one immunoreactive compound with an apparent molecular weight
      of 10,000. In the telencephalon two major species were resolved, with apparent
      molecular weights of 10,000 and 8800, and a minor one of 6500 mol. wt. In
      conclusion, the present study shows that endozepines are expressed in the rat
      brain as early as embryonic day 18 and the amount of endozepine-like material
      increases rapidly during the two days preceding birth. The results also indicate
      that diazepam-binding inhibitor is processed to different molecular forms
      depending on the brain region.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8309538
TI  - Phosphate-activated glutaminase immunoreactive synapses in the intermediolateral
      nucleus of rat thoracic spinal cord.
AB  - A monoclonal antibody against phosphate-activated glutaminase was used to
      identify glutamatergic neuronal components in the intermediolateral nucleus of
      the thoracic spinal cord of the rat. Under electron microscopy of the
      intermediolateral nucleus, most glutaminase immunoreactivity was detected in the
      axoplasm surrounding spherical synaptic vesicles in the presynaptic axon
      varicosities which formed asymmetric synapses with small dendrites and
      occasionally with neuronal cell bodies. About 40% of axon varicosities within the
      intermediolateral nucleus and 49% of the axon varicosities forming asymmetric
      synaptic contacts showed glutaminase immunoreactivity. Glutaminase
      immunoreactivity was further seen in mitochondria of neuronal perikarya and
      dendrites in the intermediolateral nucleus, and occasionally in the cytoplasm of
      the dendrites and glial processes in the vicinity of glutaminase-immunoreactive
      axon varicosities. By the combined method of immunocytochemistry and retrograde
      axonal transport, glutaminase-immunoreactive axons were shown to make direct
      synaptic contacts with the preganglionic sympathetic neurons, which were
      retrogradely labeled by injection of horseradish peroxidase conjugated with
      choleratoxin B subunit into the superior cervical ganglion. The present results
      indicate that glutaminase-containing axons are the major synaptic inputs to
      intermediolateral nucleus neurons including preganglionic sympathetic ones,
      suggesting that glutamate is used as the neurotransmitter to control those
      neurons in the intermediolateral nucleus.

PMID- 8309539
TI  - Distinct subsets of neuropeptide Y-negative principal neurons receive basket-like
      innervation from enkephalinergic and gabaergic axons in the superior cervical
      ganglion of adult rats.
AB  - The distributions of axons immunoreactive for [Leu]- or [Met]enkephalin and GABA
      were studied in the superior cervical ganglion of adult rats. The antigens were
      visualized separately and in combination with neuropeptide Y by the
      immunoperoxidase technique, using reaction end-products of different colors.
      Similarities and differences were found in the light-microscopic innervation
      patterns of enkephalin- and GABA-immunoreactive nerve fibers. Both fiber systems
      were heterogeneously distributed within the superior cervical ganglion, forming
      denser networks in its rostral part than elsewhere in the ganglion. The
      appearance of labeled nerve fibers differed in the two systems. Enkephalin
      immunoreactive axons exhibited dotted profiles due to a strong immunoreaction in
      the axonal varicosities as compared with that in the intervaricose segments,
      whereas GABA-positive fibers were evenly labeled in both parts of the axons. The
      most marked difference between the innervation patterns from enkephalin- and GABA
      immunoreactive axons was the presence of bundles of varicose axons in conjunction
      with the basket-like aggregation of enkephalin-immunoreactive nerve terminals.
      The possibility that enkephalins and GABA are co-localized in certain axons was
      excluded in double-labeling studies, silver intensification being used for the
      first antigen and the nickel-enhanced diaminobenzidine reaction for the second
      antigen. Different subsets of principal neurons were richly innervated in a
      basket-like manner by axons immunoreactive for enkephalins and GABA.
      Additionally, combined staining with antisera against either enkephalin and
      neuropeptide Y or GABA and neuropeptide Y revealed that both subsets of principal
      neurons richly innervated either by enkephalin-immunoreactive or by GABA
      immunoreactive axons were devoid of neuropeptide Y immunoreactivity. Thus, the
      enkephalinergic and GABAergic axons have different subpopulations of neuropeptide
      Y-negative principal neurons as targets in the superior cervical ganglion. These
      results provide further evidence that sympathetic ganglion cells can be
      classified on the basis of their receiving input from different sources.

PMID- 8309540
TI  - Caffeine-induced calcium release from internal stores in cultured rat sensory
      neurons.
AB  - Free intracellular calcium concentration ([Ca2+]in) was recorded at 22 degrees C
      by means of Indo-1 or Fura-2 single-cell microfluorometry in cultured dorsal root
      ganglion neurons obtained from neonatal rats. The resting [Ca2+]in in dorsal root
      ganglion neurons was 73 +/- 21 nM (mean +/- S.D., n = 94). Fast application of 20
      mM caffeine evoked [Ca2+]in transient which reached a peak of 269 +/- 64 nM
      within 5.9 +/- 1.1 s. After reaching the peak the [Ca2+]in level started to
      decline in the presence of caffeine and for 87.2 +/- 10.6 s cytoplasmic calcium
      returned to an initial resting value. In 40% of neurons tested [Ca2+]in decreased
      to subresting levels following the washout of caffeine (the so-called post
      caffeine undershoot). On average, the undershoot level was 19 +/- 2.5 nM below
      the resting [Ca2+]in value. Prolonged exposure of caffeine depleted the caffeine
      sensitive stores of releasable Ca2+; the degree of this depletion depended on
      caffeine concentration. The depletion of the caffeine-sensitive internal stores
      to some extent was linked to calcium extrusion via La(3+)-sensitive plasmalemmal
      Ca(2+)-ATPases. The stores could be partially refilled by the uptake of
      cytoplasmic Ca2+, but the complete recovery of releasable Ca2+ content of the
      caffeine-sensitive pools required the additional calcium entry via voltage
      operated calcium channels. Caffeine-evoked [Ca2+]in transients were effectively
      blocked by 10 microM ryanodine, 5 mM procaine, 10 microM dantrolene or 0.5 mM
      Ba2+, thus sharing the basic properties of the Ca(2+)-induced-Ca2+ release from
      endoplasmic reticulum. Pharmacological manipulation with caffeine-sensitive
      stores interfered with the depolarization-induced [Ca2+]in transients. In the
      presence of low caffeine concentration (0.5-1 mM) in the extracellular solution
      the rate of rise of the depolarization-triggered [Ca2+]in transients
      significantly increased (by a factor 2.15 +/- 0.29) suggesting the occurrence of
      Ca(2+)-induced Ca2+ release. When the caffeine-sensitive stores were emptied by
      prolonged application of caffeine, the amplitude and the rate of rise of the
      depolarization-induced [Ca2+]in transients were decreased. These facts suggest
      the involvement of internal caffeine-sensitive calcium stores in the generation
      of calcium signal in sensory neurons.

PMID- 8309541
TI  - Two neurotropic viruses, herpes simplex virus type 1 and mouse hepatitis virus,
      spread along different neural pathways from the main olfactory bulb.
AB  - Several neurotropic viruses enter the brain after peripheral inoculation and
      spread transneuronally along pathways known to be connected to the initial site
      of entry. In this study, the pathways utilized by two such viruses, herpes
      simplex virus type 1 and mouse hepatitis virus strain JHM, were compared using in
      situ hybridization following inoculation into either the nasal cavity or the main
      olfactory bulb of the mouse. The results indicate that both viruses spread to
      infect a unique and only partially overlapping set of connections of the main
      olfactory bulb. Both quantitative and qualitative differences were observed in
      the patterns of infection of known primary and secondary main olfactory bulb
      connections. Using immunohistochemistry for tyrosine hydroxylase combined with in
      situ hybridization, it was shown that only herpes simplex virus infected
      noradrenergic neurons in the locus coeruleus. In contrast, both viruses infected
      dopaminergic neurons in the ventral tegmental area, although mouse hepatitis
      virus produced a more widespread infection in the A10 group, as well as infecting
      A8 and A9. The results suggest that differential virus uptake in specific
      neurotransmitter systems contributes to the pattern of viral spread, although
      other factors, such as differences in access to particular synapses on infected
      cells and differences in the distribution of the cellular receptor for the two
      viruses, are also likely to be important. The data show that neural tracing with
      different viruses may define unique neural pathways from a site of inoculation.
      The data also demonstrate that two viruses can enter the brain via the olfactory
      system and localize to different structures, suggesting that neurological
      diseases involving disparate regions of the brain could be caused by different
      viruses, even if entry occurred at a common site.

PMID- 8309542
TI  - Action of endogenous oxytocin within the paraventricular or supraoptic nuclei: a
      powerful link in the regulation of the bursting pattern of oxytocin neurons
      during the milk-ejection reflex in rats.
AB  - During suckling, the periodic and synchronous bursting activity of oxytocin
      neurons has been shown to be facilitated by oxytocin itself, acting via several
      target sites, including the magnocellular nuclei. To investigate the role of the
      endogenous oxytocin released within the magnocellular nuclei during the milk
      ejection reflex in the rat, an oxytocin antagonist (50 microM solution of
      [d(CH2)5, Tyr(Me)2,Orn8]-vasotocin was pressure-injected into either one
      paraventricular or one supraoptic nucleus while recording the bursting pattern of
      oxytocin neurons within the injected nucleus and within a contralateral nucleus.
      The oxytocin antagonist was injected either during an ongoing milk-ejection
      reflex or during its facilitation induced by oxytocin (1 microliter of 1 microM
      solution injected into the third ventricle, i.e. 1 ng). During an ongoing milk
      ejection reflex, injections of the oxytocin antagonist (10 nl of 50 microM
      solution, i.e. 50 ng) into the paraventricular or supraoptic nucleus decreased
      (more than 20% change) the burst amplitude (total number of spikes/burst) of
      neurons within the injected nucleus in 100% of tests, and simultaneously of
      contralateral neurons in 68% of tests. Burst periodicity of the entire population
      was also decreased in 50% of tests whatever the nucleus injected, but burst
      desynchronization was never observed. Successive injections of minute volumes of
      oxytocin (10 nl of 10 microM solution, i.e. 0.1 ng) into the paraventricular or
      supraoptic nucleus (which will progressively affect a greater number of neurons)
      first increased burst amplitude of oxytocin neurons within the injected nucleus
      and then increased simultaneously burst amplitude of contralateral neurons and
      burst frequency of the whole oxytocin neuron population. All these results
      suggest that the recruitment of a critical number of oxytocin neurons within one
      nucleus induces changes in the bursting activity of the oxytocin neurons in the
      four magnocellular nuclei. Within the minute following an intracerebroventricular
      oxytocin injection, the oxytocin antagonist injected into the supraoptic nucleus
      not only prevented the oxytocin-induced facilitation but also completely
      interrupted the milk-ejection reflex. When injected into the paraventricular
      nucleus, the oxytocin antagonist was less efficient: it decreased the oxytocin
      induced facilitation but the reflex was not blocked. Similar partial inhibitory
      effect (decrease in burst amplitude and burst frequency) was also observed when
      the oxytocin antagonist was injected into the supraoptic nucleus after
      facilitation of the milk-ejection reflex by intracerebroventricular oxytocin
      injection. In conclusion, endogenous oxytocin released within the magnocellular
      nuclei during suckling represents a necessary link of the neuronal network
      regulating the bursting activity of oxytocin neurons.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8309543
TI  - Distribution of GABA immunoreactivity in the amygdaloid complex of the cat.
AB  - This study describes the distribution of GABA immunoreactivity in the amygdaloid
      complex of cats. At the light microscopic level, immunopositive structures
      consisted of morphologically diverse somata and numerous small punctate elements.
      The latter accounted for most of the staining at low magnification and, at the
      electron microscopic level, were found to be axon terminals establishing
      symmetric synaptic contacts with a variety of postsynaptic profiles. Deep and
      superficial amygdaloid nuclei could be assigned to one of four groups according
      to (i) the intensity of immunolabeling they displayed, (ii) their density in
      reactive somata, and (iii) the size of the immunopositive somata they contained.
      Intercalated cell masses displayed the highest density of strongly immunoreactive
      cell bodies and presumed GABAergic terminals. However, electron microscope
      observations showed that intercalated somata were almost devoid of synaptic
      contacts. In contrast, central and medial nuclei were characterized by a low
      density of intensely immunoreactive somata and an elevated concentration for
      GABAergic terminals which contacted somatic and dendritic profiles. In addition,
      central and medial nuclei contained numerous neurons displaying low to moderate
      immunoreactivity. Superficial amygdaloid nuclei and nuclei of the basolateral
      complex displayed an intermediate density of immunoreactive somata and a low to
      moderate concentration of presumed terminals. Analysis of the distribution of
      soma areas within these nuclei revealed that the basolateral complex contains a
      distinct subpopulation of larger immunoreactive neurons. In light of recent
      electrophysiological findings, these results suggest that the intra-amygdaloid
      GABAergic system plays a major role in controlling the synaptic responsiveness
      and spontaneous activity of amygdaloid neurons.

PMID- 8309544
TI  - The intercalated cell masses project to the central and medial nuclei of the
      amygdala in cats.
AB  - In order to study the efferent projections of the intercalated cell masses within
      the amygdaloid complex, iontophoretic injections of cholera toxin B subunit were
      performed in several amygdaloid nuclei of the centromedial and basolateral groups
      in cats. Analysis of the ensuing retrograde labeling revealed that the main intra
      amygdaloid targets of the intercalated cell masses are the central and medial
      nuclei. Most intercalated neurons projecting to the medial nucleus were found in
      the larger, rostrally located intercalated cell masses. In contrast, the majority
      of intercalated cells projecting to the central medial and central lateral nuclei
      were found in the smaller, caudally located intercalated cell masses. In
      addition, evidence for weaker projections to the basolateral nucleus and other
      intercalated cell masses was obtained. In light of previous immunohistochemical
      results showing that GABAergic cells represent the main cell type in the
      intercalated cell masses, these results imply that the intercalated cell masses
      constitute an important source of GABAergic input to the centromedial complex.
      The significance of this finding lies in the fact that the intercalated cell
      masses are located at the interface between the basolateral nuclear group and the
      centromedial complex, the main route through which the amygdaloid complex can
      directly influence hypothalamic and brainstem centers involved in the elaboration
      of autonomic responses and species-specific emotional behaviors.

PMID- 8309545
TI  - Bilateral communication between vestibular labyrinths in pigeons.
AB  - Extracellular action potentials from single horizontal semicircular canal primary
      afferent fibers were recorded in paralysed decerebrate pigeons during pulse
      mechanical stimulation of the contralateral horizontal semicircular canal. Clear
      responses to the contralateral membranous duct displacement stimuli were observed
      in 51% of the tested 158 horizontal semicircular canal afferents. Generally,
      three different types of responses were obtained in the primary afferent fibers
      including excitation, inhibition, and a few complex type neural activity
      profiles. Inhibitory responses were of larger amplitude and had longer time
      constants than did excitatory responses. The few complex type responses observed
      were characterized by an initial excitatory discharge followed by a longer
      duration decrease in the fiber's firing rate. The sensitivity to stimulation and
      type of response obtained for each afferent was significantly correlated with the
      fiber's coefficient of variation value. Regular firing afferents were less
      sensitive and exhibited primarily excitatory responses (71%) to contralateral
      canal stimulation. Irregular firing afferents were more sensitive and exhibited
      mostly inhibitory responses (84%). The present results demonstrate that a
      communication network for information exchange between the bilateral labyrinths
      exists in pigeons. The observed responses in primary afferent fibers to
      contralateral horizontal semicircular canal stimulation are proposed to be
      mediated by the vestibular efferent system, which could provide an anatomical
      pathway for information exchange from vestibular receptors on opposite sides of
      the head.

PMID- 8309546
TI  - Mouse fetal trisomy 13 and hypotrophy of the spinal cord: effect on calbindin
      D28k and calretinin expressed by neurons of the spinal cord and dorsal root
      ganglia.
AB  - Trisomy 13 was detected in 10% of mouse embryos obtained from pregnant females
      which were doubly heterozygous for Robertsonian chromosomes involving chromosome
      13. The developing dorsal root ganglia and spinal cords were examined in trisomy
      13 and littermate control mice between days 12 and 18 of gestation (E12-18). The
      overall size of the dorsal root ganglia and number of ganglion cells within a
      given ganglion were not altered, but the number of neurons immunoreactive for
      calbindin and calretinin was reduced. The trisomic spinal cord was reduced in
      size with neurons lying in a tightly compact distribution in the gray matter. In
      trisomic fetuses, the extent of the neuropil of the spinal cord was reduced, and
      may represent a diminished field of interneuronal connectivity, due to reduced
      arborization of dendritic processes of the neurons present, particularly of
      calbindin-immunostained neurons. Furthermore, the subpopulation of calretinin
      immunoreactive neurons and axons was also reduced in developing trisomic gray and
      white matter, respectively. Thus, overexpression of genes on mouse chromosome 13
      exerts a deleterious effect on the development of neuropil, affecting both
      dendritic and axonal arborization in the trisomy 13 mouse. The defect of
      calbindin or calretinin expression by subsets of dorsal root ganglion or spinal
      cord neurons may result from deficient cell-to-cell interactions with targets
      which are hypoplastic.

PMID- 8309547
TI  - Regulated cleavage of Alzheimer beta-amyloid precursor protein in the absence of
      the cytoplasmic tail.
AB  - Alzheimer beta-amyloid precursor protein can be phosphorylated on residues
      Thr654, Ser655 and Thr668 on its cytoplasmic domain. Proteolytic cleavage of the
      amyloid precursor protein and release of the amyloid precursor protein ectodomain
      into the medium of cultured cells can be activated by phorbol esters which
      stimulate protein kinase C. In the present study, using mutated amyloid precursor
      protein, we show that phosphorylation of cytoplasmic residues is not required for
      the phorbol ester-activated cleavage and release of the amyloid precursor protein
      ectodomain. Remarkably, deletion of the entire amyloid precursor protein
      cytoplasmic tail had no effect on the phorbol ester-activated cleavage/release.
      The results indicate that activation of amyloid precursor protein
      cleavage/release by protein kinase C involves phosphorylation of some component
      of the processing pathway, instead of or in addition to the cytoplasmic tail of
      the amyloid precursor protein.

PMID- 8309548
TI  - Modulation of opiate responses in brain noradrenergic neurons by the cyclic AMP
      cascade: changes with chronic morphine.
AB  - It has been recently reported that the cyclic AMP cascade substantially modulates
      excitatory amino acid and d-aminobutyric acid responses in central neurons.
      Furthermore, interactions between the cyclic AMP system and opiate receptors have
      been well documented. The modification of neuronal responsiveness to opiates
      through such a second messenger system could be important in both normal
      functioning of opioid neurotransmitter systems and in opiate abuse. As the
      noradrenergic nucleus locus coeruleus receives a prominent endogenous opioid
      innervation and is thought to be important in brain mechanisms of opiate abuse,
      we examined opiate responses in locus coeruleus neurons following activation of
      the cyclic AMP cascade. We report that opiate responses of locus coeruleus
      neurons are enhanced by forskolin, an activator of adenylate cyclase, and by
      intracellular application of cyclic AMP. This potentiation of the opiate response
      was blocked by protein kinase inhibitors, which also depressed opiate responses
      below baseline values. Forskolin also potentiated responses to the a2
      adrenoceptor agonist, clonidine, but did not consistently potentiate opiate
      responses in locus coeruleus neurons from rats chronically treated with morphine.

PMID- 8309549
TI  - Intermittent release of noradrenaline by single pulses and release during short
      trains at high frequencies from sympathetic nerves in rat tail artery.
AB  - As shown by electrophysiological analysis, the release of the sympathetic co
      transmitter adenosine 5'-triphosphate (ATP) from individual release sites is
      monoquantal and intermittent; the average release probability may be as low as
      0.01. Indirect evidence from biochemical studies of noradrenaline overflow is
      compatible with a similar monoquantal, low probability release of noradrenaline
      as well. In the present study our first aim was to address this issue more
      directly in rat tail artery, using continuous amperometry to monitor in real time
      the release of noradrenaline from a relatively small number of sympathetic nerve
      varicosities. The results seem to provide the first direct evidence that
      noradrenaline, similarly to ATP, may be released intermittently during nerve
      stimulation at low frequency. Our second aim was to use the same technique to
      study the release of noradrenaline caused by nerve stimulation with single pulses
      or short trains (two to eight pulses) at high frequencies. The results show that
      during stimulation at 20 Hz the peak amplitude of the noradrenaline oxidation
      current response grew linearly with the train length, but at 50 Hz the curve
      describing this growth was sigmoid in shape.

PMID- 8309550
TI  - Entorhinal cortex regulation of multiple brain-derived neurotrophic factor
      promoters in the rat hippocampus.
AB  - Developmental or degenerative damage of the neuronal architecture in the
      entorhinal cortex may disintegrate a functional part of hippocampal input since
      the entorhinal cortex provides a major source of neocortical and subcortical
      input to the hippocampus. These alterations, such as seen in Alzheimer's disease,
      schizophrenia and temporal lobe epilepsy are likely to be associated with
      cognitive deficits. To understand the basis for pathological changes in the
      corticohippocampal loop it is important to study mechanisms involved in neuronal
      plasticity. Brain-derived neurotrophic factor provides a possible substrate to
      mediate such plasticity. We have previously provided evidence that stimulation of
      hippocampal afferents transynaptically increase the level of brain-derived
      neurotrophic factor messenger RNA within the hippocampus. In the present study we
      have investigated whether different brain-derived neurotrophic factor messenger
      RNAs are specifically regulated in the hippocampus. We provide evidence for a
      differential and dose-dependent regulation of the different brain-derived
      neurotrophic factor promoters in the hippocampus by afferents in the entorhinal
      cortex. Our finding of a graded regulation is in contrast to earlier evidence of
      an "all-or-none" type of regulation.

PMID- 8309551
TI  - Increased expression of trkB and trkC messenger RNAs in the rat forebrain after
      focal mechanical injury.
AB  - Tyrosine protein kinases trkA, trkB and trkC are signal transduction receptors
      for a family of neurotrophic factors known as the neurotrophins. Here we report
      on changes in the expression of messenger RNAs for trkA, trkB and trkC in the
      brain following an injury caused by insertion of a 30-gauge needle into adult rat
      hippocampus or neocortex. Quantitative in situ hybridization revealed no change
      in the level of trkA messenger RNAs in any brain region following this insult. In
      contrast, increased levels of trkB messenger RNA compared to untreated animals
      were seen in the granule cell layer of the dentate gyrus ipsilateral to the
      injury already 30 min after the injury. The increase reached maximal levels (four
      fold) between 2 and 4 h, but returned to control levels 8 h after the injury. No
      change was seen in the contralateral dentate gyrus. The levels of trkC messenger
      RNA increased in the same brain regions as trkB messenger RNA, though with a
      delayed response, reaching a maximal increase of 3.3-fold 4 h after the injury.
      As for trkB messenger RNA, the level of trkC messenger RNA then tapered off and
      reached control levels 8 h after the injury. However, 4 h after the injury, a 1.7
      fold increase of trkB and trkC messenger RNAs were seen in the ipsilateral
      piriform cortex. The increases of trkB and trkC messenger RNAs were confirmed
      using a nuclease protection assay. Increases of both trkB and trkC messenger RNAs
      were also seen in the piriform cortex, but not in the hippocampus, following
      needle insertion into the neocortex. Pretreatment of the animals with the non
      competitive N-methyl-D-aspartate antagonist ketamine completely prevented the
      increases of trkB and trkC messenger RNAs, suggesting that the brain injury
      caused a release of glutamate with subsequent activation of N-methyl-D-aspartate
      receptors. In contrast, the anticonvulsive drug diazepam, the muscarinic
      antagonist atropine and the calcium-channel antagonist nimodipine had no effect
      on the increases of trkB and trkC messenger RNAs. Combined with previous data on
      the expression of neurotrophin messenger RNAs following similar injuries, our
      results support the hypothesis that increased levels of neurotrophins and their
      receptors could protect against neuronal damage following a brain insult.

PMID- 8309552
TI  - Fast and widespread increase of basic fibroblast growth factor messenger RNA and
      protein in the forebrain after kainate-induced seizures.
AB  - Basic fibroblast growth factor promotes the survival and outgrowth of neurons and
      protects neurons from glutamate mediated excitotoxicity. The present study
      investigates the effects of kainate-induced epileptic seizures on the cellular
      expression of basic fibroblast growth factor messenger RNA and protein. Seizures
      were induced by injection of 12 mg/kg kainic acid. Rats were killed 3 h, 6 h, and
      24 h after injection of the drug and analysed by radioactive and non-radioactive
      in situ hybridization as well as immunohistochemistry for glial fibrillary acidic
      protein and basic fibroblast growth factor. Radioactive in situ hybridization
      revealed a fast (6 h), strong (300-400% of control) and widespread increase of
      basic fibroblast growth factor messenger RNA after kainate-induced seizures. Non
      radioactive in situ hybridization using digoxigenin-labeled riboprobes combined
      with glial fibrillary acidic protein immunohistochemistry showed that basic
      fibroblast growth factor messenger RNA was markedly increased in astroglial cells
      throughout the brain. Immunohistochemistry for basic fibroblast growth factor
      revealed labeling of nuclei in astrocytes in many forebrain areas and in neurons
      in area CA2 and fasciola cinereum. Kainate markedly increased basic fibroblast
      growth factor-like immunoreactivity in nuclei of astrocytes in several forebrain
      areas. This effect peaked 24 h after injection. It is concluded that basic
      fibroblast growth factor may play a neuroprotective role in kainate mediated
      excitotoxicity as seen from a massive and widespread astroglial increase in basic
      fibroblast growth factor messenger RNA and -like immunoreactivity. These effects
      may, to a large degree, be mediated through the excessive release of endogenous
      glutamate, induced by the epileptic seizures, leading to activation of glutamate
      receptors on astroglial cells through volume transmission, i.e. via diffusion of
      electrochemical signals in the extracellular fluid pathways.

PMID- 8309553
TI  - Chronic nicotine treatment counteracts nigral cell loss induced by a partial
      mesodiencephalic hemitransection: an analysis of the total number and mean volume
      of neurons and glia in substantia nigra of the male rat.
AB  - This study combines immunocytochemical and stereological methods for the first
      time to obtain unbiased estimates of the number of cells in the entire substantia
      nigra and their respective mean volume. Nicotine, delivered by subcutaneously
      implanted osmotic pumps (0.125 mg/kg/h, 14 days) to male Sprague-Dawley rats with
      a partial unilateral mesodiencephalic lesion, caused a significant counteraction
      of the lesion-induced reduction in total number of nigral tyrosine hydroxylase
      like immunoreactive neurons counterstained with Cresyl Violet compared with
      saline treated control animals. The number of Nissl stained neurons without
      tyrosine hydroxylase-like immunoreactivity was not affected by the lesion nor by
      nicotine. The numbers of non-neuronal glial fibrillary acidic protein-like
      immunoreactive cells counterstained with Cresyl Violet and smaller cells seen
      after Cresyl Violet staining alone, possibly representing microglia, were
      increased by the lesion but not affected by nicotine. No nicotine-induced effects
      were found on the number of nigral cells located contralateral to the lesion. The
      lesion-induced reduction in the mean volume of the nigral cells showing tyrosine
      hydroxylase-like immunoreactivity, as determined with the stereological rotator
      method, was not affected by nicotine. These findings suggest that continuous
      nicotine infusion exerts protective effects on lesioned nigroneostriatal dopamine
      systems and that these protective effects are selective for the nigral dopamine
      neurons not affecting other populations of neurons or non-neuronal cells. This
      neuroprotective effect might lead to new therapeutic strategies in clinical
      neurodegenerative disorders such as Parkinson's Disease.

PMID- 8309554
TI  - The segregation and expression of glutamate receptor subunits in cultured
      hippocampal neurons.
AB  - The distribution and expression of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate-selective glutamate receptor subunits (GluR1-4) were studied
      in cultured hippocampal neurons using antibodies generated against peptides
      corresponding to the C-termini of GluR1, GluR2/3 and GluR4, and with a set of
      oligonucleotide probes designed complementary to specific pan, flip and flop
      GluR1-4 messenger RNA sequences. GluR1-4 subunit proteins were localized in fixed
      hippocampal neurons (2 h to three weeks after plating) by immunocytochemistry
      with light and electron microscopy. At early stages in culture, moderate staining
      with antibodies to GluR1 and GluR2/3 and very light staining with antibody to
      GluR4 was observed in cell bodies and proximal portions of all neurites of some
      neurons. Upon establishment of identified axons and dendrites by seven days in
      culture, staining was intense with specific antibodies to GluR1 and GluR2/3 and
      light with anti-GluR4 antibody in cell bodies and dendrites. Little or no
      staining was observed in axons. Cells at seven days in culture exhibited a
      variety of morphologies. However, we could not assign a pattern of staining to a
      particular type. As the cultures matured over two and three weeks, staining was
      limited to the somatodendritic compartment. The intensity of glutamate receptor
      subunit staining increased and the extent of staining proceeded to the distal
      extreme of many dendrites. Moreover, antibodies to GluR1-4 subunits were co
      localized in neurons. Immunocytochemistry on living neurons did not result in any
      significant labeling, suggesting that the epitope is either not expressed on the
      surface of the neurons, or is present, but inaccessible to the antibody. Electron
      microscopy demonstrated receptor localization similar to that found in brain,
      with staining of postsynaptic membrane and density, dendritic cytoplasm and cell
      body, but not within the synaptic cleft. We examined the possible role of
      "cellular compartmentation" in the pattern of glutamate receptor expression in
      hippocampal neurons. Compartmentalization studies of the subcellular distribution
      of messenger RNAs encoding GluR1-4 subunits was determined in mature cultures by
      in situ hybridization. Significant silver grain appearance was restricted to the
      cell body, indicating that the synthesis of glutamate receptor subunits is
      limited largely to the neuronal cell body. The expression of microtubule
      associated protein 2 was studied in parallel. Microtubule-associated protein 2
      expression appeared 6 h after plating, while glutamate receptor subunit
      expression was present at 2 h. This indicates that microtubule-associated protein
      2 does not regulate the initial distribution of glutamate receptor subunits into
      neurites.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8309555
TI  - Apoptotic cell death occurs in hippocampal neurons cultured in a high oxygen
      atmosphere.
AB  - When embryonic rat hippocampal neurons were cultured in a 50% oxygen atmosphere,
      neurons gradually died after 20 h in culture. This death pattern was found to be
      mediated by an intracellular active death program, so called apoptosis, as
      follows: (1) Cycloheximide and actinomycin-D, protein and RNA synthesis
      inhibitors, respectively, prevented cell death, indicating that cell death
      required new protein biosynthesis. (2) DNA fragmentation (called a "DNA ladder"),
      a specific biochemical marker of apoptosis, was detected during the course of
      cell death. (3) Depolarization with high K+ medium (26-50 mM) prevented cell
      death. This effect was suppressed by some dihydropyridine derivatives, L-type Ca
      channel blockers, such as nifedipine and nicardipine. These results indicate that
      increased levels of oxygen activate an apoptotic mechanism in the cultured
      hippocampal neurons, and suggest that neuronal activity may protect the neurons
      from oxygen-induced apoptosis.

PMID- 8309556
TI  - Lesion-induced neurite sprouting and synapse formation in hippocampal organotypic
      cultures.
AB  - By sectioning, using a razor blade, one- and three-week-old rat hippocampal
      organotypic cultures, we have tested the possibility that neurite outgrowth and
      reactive synaptogenesis would take place even after several weeks in culture in
      this in vitro model. At the light-microscopic level, recovery from the section
      and formation of a thin scar were observed within six days following the lesion.
      Immunostainings using neurofilament antibodies showed the presence of numerous
      degenerative and regenerative images one day after the cut and many fibres
      crossing the section six days after the lesion. Electrophysiological recordings
      of synaptic responses elicited across the section indicated the formation of new
      functional synaptic contacts and complete recovery of transmission within three
      to six days. Interestingly, functional recovery in three-week-old cultures was
      found to be significantly slower than in one-week-old tissue. These findings were
      confirmed at the electron-microscopic level. Evidence was obtained for an
      effective cleaning of the lesion site by macrophages and astroglial cells, the
      existence of many degenerative and regenerative images one day after the cut and
      the presence of new dendrites, axonal fibres and synapses in the area of the
      section six days after the lesion. All these changes were slower in three- than
      in one-week-old cultures. These results indicate that organotypic cultures can be
      used as an interesting model for studies of reactive synaptogenesis.

PMID- 8309557
TI  - Evidence for age-dependent changes in motoneuron dendritic morphology following
      neonatal nerve-crush in the rat.
AB  - Motoneurons supplying the extensor hallucis longus muscle of the rat were
      temporarily separated from the muscle by sciatic nerve-crush at five days
      postnatally. Such treatment permanently alters the reflex response of the
      affected motoneurons without the large-scale cell death associated with nerve
      crush at birth. After reinnervation, the motoneurons were retrogradely labelled
      with cholera toxin subunit-B conjugated to horseradish peroxidase and the
      dendritic tree of each labelled cell was analysed. When compared to normal data,
      significantly higher levels of dendritic density were observed in the
      rostrodorsally orientated parts of the dendritic field. This was similar to that
      found previously for the same motor pool after nerve-crush at birth. However, in
      other parts of the field where a lower dendritic density was found after nerve
      crush at birth, no change was seen after nerve-crush at five days. These data
      present evidence for the influence of sensory afferents on the development of
      motoneuron dendrites. Taken together with the previous findings after nerve-crush
      at birth, we suggest that the differential dendritic changes caused by neonatal
      nerve lesion contribute to an imbalance in the pattern of excitatory and
      inhibitory inputs to the motoneuron, which results either in cell death, or the
      abnormal activity seen in those motoneurons which survive.

PMID- 8309558
TI  - Schaltenbrand and Hallervorden.

PMID- 8309559
TI  - Methodology in neuroanatomic measurement.

PMID- 8309560
TI  - Neurology, psychiatry, and neuropsychiatry.

PMID- 8309561
TI  - The brain in infantile autism: posterior fossa structures are abnormal.
AB  - Infantile autism is a neurologic disorder of social, cognitive, and language
      development. Earlier MRI studies found hypoplasia of posterior vermal lobules VI
      and VII and cerebellar hemispheres in the majority of autistic patients, and
      recent autopsy analyses find severe Purkinje neuron loss in the posterior vermis
      (lobules VI and VII and VIII to X) and hemispheres. A second type of cerebellar
      pathology in infantile autism was recently found: hyperplasia (excessive
      enlargement) of posterior vermal lobules VI and VII. If the autistic samples in
      some MRI studies that did not detect cerebellar hypoplasia were actually composed
      of both the hypoplasia and hyperplasia subtypes, then the autistic mean size
      reported in such studies would have appeared to be near the normal mean size only
      because it would be the sum of the two opposite subtypes. To test this
      possibility, we statistically reanalyzed previously published vermal area
      measures of 78 autistic patients from four separate studies. The results revealed
      that the autistic patient samples from these four studies were indeed composed of
      both the hypoplasia subtype (87%, 92%, 89%, and 84% of patients) and the
      hyperplasia subtype (13%, 8%, 11%, and 16% of patients). Cerebellar abnormalities
      have been found in 15 autopsy and quantitative MRI reports from nine laboratories
      involving a total of 226 autistic cases. Autism may be one of the first
      developmental neuropsychiatric disorders for which substantial concordance exists
      among several independent microscopic and macroscopic studies as to the location
      and type of neuroanatomic maldevelopment. Onset might be as early as the second
      trimester. Discovery of the etiologies underlying cerebellar maldevelopment may
      be the key to uncovering some of the causes of infantile autism.

PMID- 8309562
TI  - High-dose intravenous immunoglobulin and serum viscosity: risk of precipitating
      thromboembolic events.
AB  - High-dose intravenous immunoglobulin (IVIg) can increase blood viscosity in vitro
      and has been associated with cardiovascular or cerebrovascular thromboembolism.
      Because thromboembolic events were observed in two (3%) of 65 patients we treated
      with IVIg, we measured serum viscosity serially in 13 patients (five with
      amyotrophic lateral sclerosis [ALS], eight with IgM paraproteinemic
      polyneuropathy) before and immediately after each of three consecutive monthly
      infusions of IVIg. We correlated changes in viscosity with serial determinations
      of the total serum IgG, IgM, and IgA before and after each infusion. Serum
      viscosity increased after IVIg in all the patients by 0.1 to 1.0 centipoise (cp)
      (mean, 0.55 cp). In three ALS patients and in all the patients with
      paraproteinemic polyneuropathy, serum viscosity exceeded the upper limit of
      normal (normal, 1.5 to 1.9 cp) and increased as high as 2.6 cp. The increase in
      viscosity occurred immediately after completion of the infusion, declined over 1
      month, and appeared to correlate best with the serum IgG level, which after the
      infusions was as high as 6,160 mg/dl (normal, 545 to 1,560 mg/dl). I conclude
      that IVIg increases serum viscosity and in many patients can cross the
      symptomatic threshold level. Because increased serum viscosity can impair blood
      flow and trigger a cardiovascular or cerebrovascular thromboembolic event, IVIg
      should be used judiciously and with concurrent monitoring of serum viscosity in
      elderly patients and patients with cryoglobulinemia, monoclonal gammopathies,
      high lipoproteins, or preexisting vascular disease.

PMID- 8309563
TI  - Inverse association of anti-inflammatory treatments and Alzheimer's disease:
      initial results of a co-twin control study.
AB  - We conducted a co-twin control study among 50 elderly twin pairs with onsets of
      Alzheimer's disease (AD) separated by 3 or more years. Twenty-three male pairs
      (46%) were screened from the (U.S.) National Academy of Sciences-National
      Research Council Registry (NAS-NRC Registry) of World War II veteran twins;
      others (mostly women) had responded to advertisements or were referred from AD
      clinics. Twenty-six pairs (52%) were monozygous. The onset of AD was inversely
      associated with prior use of corticosteroids or ACTH (odds ratio [OR], 0.25; 95%
      confidence interval [CI], 0.06 to 0.95; p = 0.04). Similar but weaker trends were
      present among pairs discordant for history of arthritis or for prior daily use of
      nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. The association was
      strongest when we combined use of steroids/ACTH or NSAIDs post hoc into a single
      variable of anti-inflammatory drugs (AIs) (OR, 0.24; CI, 0.07 to 0.74; p = 0.01).
      The inverse relation was strong in female (volunteer) twin pairs but was not
      present in the younger men from the NAS-NRC Registry. AIs had typically been
      taken for arthritis or related conditions, but a similar result was apparent
      after controlling statistically for the arthritis variable (OR, 0.08; CI, 0.01 to
      0.69; p = 0.02). AIs have been proposed as a means of retarding the progression
      of AD symptoms, and these data suggest that AIs may also prevent or delay the
      initial onset of AD symptoms. Because of limitations in the case-control method,
      our results require corroboration with hypothesis-driven research designed to
      control bias and confounding.

PMID- 8309564
TI  - Cognitive impairment in adults with Down's syndrome: similarities to early
      cognitive changes in Alzheimer's disease.
AB  - Postmortem studies of brains from adults with Down's syndrome (DS) reveal a
      dramatic age-dependent increase in the incidence of neuropathology associated
      with Alzheimer's disease (AD). By the age of 40 years, virtually all DS
      individuals have AD neuropathology. Documentation of cognitive correlates of this
      phenomenon has been difficult, partly because of the preexisting mental
      retardation in DS. In the current study, we compared a group of adults with DS,
      22 to 51 years old, with a matched control group on various behavioral measures
      such as savings scores, which are known to be sensitive in detecting early
      dementia in AD patients. By using the short delayed savings score from the
      California Verbal Learning Test (a test of verbal memory), a subgroup of DS
      adults was identified as memory-impaired. This group demonstrated a decline in
      performance on various other cognitive tests with advancing age, whereas another
      group identified as having non-memory-impaired DS, and the non-DS controls,
      showed no evidence of decline with age. These results provide evidence for the
      presence of early dementia among adults with DS within an age range in which
      neuropathologic manifestations of AD are predicted to be developing.

PMID- 8309565
TI  - Cross-national interrater agreement on the clinical diagnostic criteria for
      dementia. WHO-PRA Age-Associated Dementia Working Group, WHO-Program for Research
      on Aging, Health of Elderly Program.
AB  - We assessed the interobserver agreement on the clinical diagnosis of dementia
      syndrome and dementia subtypes as part of a cross-national project on the
      prevalence of dementia. Fourteen clinicians from the participating countries
      (Canada, Chile, Malta, Nigeria, Spain, and the United States) independently
      assessed the diagnosis of 51 patients whose clinical information was in standard
      records written in English. We used the DSM-III-R and ICD-10 criteria for
      dementia syndrome, the NINCDS-ADRDA criteria for Alzheimer's disease (AD), and
      the ICD-10 criteria for other dementing diseases, and measured interobserver
      agreement. We found comparable levels of agreement on the diagnosis of dementia
      using the DSM-III-R (kappa = 0.67) as well as the ICD-10 criteria (kappa = 0.69).
      Cognitive impairment without dementia was a major source of disagreement (kappa =
      0.10). The kappa values were 0.58 for probable AD, 0.12 for possible AD, and rose
      to 0.72 when the two categories were merged. The interrater reproducibility of
      the diagnosis of vascular dementia was 0.66 in terms of kappa index; the
      diagnoses of other dementing disorders as a whole reached a kappa value of 0.40.
      This study suggests that clinicians from different cultures and medical
      traditions can use the DSM-III-R and the ICD-10 criteria for dementia effectively
      and thus reliably identify dementia cases in cross-national research. The
      interrater agreement on the diagnosis of dementia might be improved if clear-cut
      guidelines in the definition of cognitive impairment are provided. To improve the
      reliability of AD diagnosis in epidemiologic studies, we suggest that the NINCDS
      ADRDA "probable" and "possible" categories be merged.

PMID- 8309566
TI  - Sexual dysfunction in partial epilepsy: a deficit in physiologic sexual arousal.
AB  - Men and women with epilepsy frequently complain of sexual dysfunction. We studied
      the sexual response in men and women with partial epilepsy of temporal lobe
      origin (TLE) by measuring genital blood flow (GBF) during sexual arousal. Nine
      women and eight men with TLE and 12 women and seven men as controls completed
      inventories for symptoms of depression, sexual experience, and sexual attitude
      and underwent measurement of digital pulse and GBF during alternating segments of
      sexually neutral and erotic videotape. Subjective ratings of arousal to the
      videotape were obtained. We calculated digital pulse and GBF response as the
      percentage increase in pulse amplitude during the erotic compared with the
      preceding sexually neutral film. No subject group reported symptoms of
      significant depression on the inventory. However, men and women with epilepsy had
      fewer sexual experiences than subjects without epilepsy, and women with epilepsy
      imagined specific sexual activities to be more anxiety-producing and less
      arousing than did women without epilepsy. Men and women with TLE had a diminished
      GBF response. The mean increase in GBF in men with TLE was 184% versus 660% for
      controls (p = 0.01). Women with TLE had a mean increase of 117% versus 161% for
      controls (p < 0.01). Digital pulse did not vary across stimulus conditions.
      Subjective ratings for all groups indicated moderate sexual arousal. We conclude
      that there is a diminution in one aspect of physiologic sexual arousal in some
      men and women with TLE.

PMID- 8309567
TI  - High-dose intravenous immunoglobulin therapy in chronic progressive lumbosacral
      plexopathy.
AB  - Previous reports of primary lumbosacral plexopathy (LSP) have stressed the benign
      nature of the syndrome. No effective treatment is known for the occasional
      patients who do not recover or who have relapses. We report two patients
      presenting with a progressive form of idiopathic LSP. Both patients showed
      remarkable improvement on high-dose intravenous immunoglobulin therapy. We
      suggest that these patients represent a treatable subgroup of LSP.

PMID- 8309568
TI  - Prevalence of dementia in old age: clinical diagnoses in subjects aged 95 years
      and older.
AB  - Epidemiologic studies have consistently shown an exponential increase in the
      prevalence of dementia in the very old, but different standards of the
      investigators and the instruments, as well as the selection of the samples, limit
      the comparison of these studies. They usually include only a small number of
      participants aged 90 years and older. This investigation focuses on whether there
      is an exponential increase in the prevalence of dementia in people aged 90 years
      and older. The Berlin Aging Study (BASE) consists of a representative sample of
      elderly aged 70 to 105 years stratified by age and gender. Analyses of a BASE
      first sample (N = 156) with 52 participants aged 90 years and older showed an
      exponential increase in dementia from age 70 up to age 94 years, but the group
      aged 95 years and older (N = 26) showed a plateau near 45%, with no further
      increase in dementia prevalence.

PMID- 8309569
TI  - Occipitotemporal seizures with ictus emeticus induced by intermittent photic
      stimulation.
AB  - We recorded occipitotemporal seizures induced by intermittent photic stimulation
      in three children with brain injuries, aged 10 to 13 years. All had a history of
      seizures and showed occipital spikes on EEG, but were seizure free and were not
      being treated at the time of investigation. In all, photic stimulation induced
      seizures in the right occipital lobe. They were followed by clinical and EEG
      signs suggesting infrasylvian spreading to ipsilateral mesiotemporal limbic
      structures and by vomiting, appearing at late stages of the attacks. Seizure
      spread was very slow in two patients in whom attacks lasted 16 and 25 minutes.
      Patients with occipital epileptiform abnormalities presenting with ictal vomiting
      are often diagnosed as having vague migraine-epilepsy syndromes. We conclude that
      vomiting can be a late ictal phenomenon resulting from temporal lobe spread of
      seizures originating in the occipital lobe.

PMID- 8309570
TI  - Observations on the short-term 'natural history' of probable Alzheimer's disease
      in a controlled clinical trial.
AB  - We examined the performance of patients with probable Alzheimer's disease (AD)
      who participated in the placebo arm of a 12-week clinical trial. Assessments
      occurred at baseline and at 4, 6, 10, and 12 weeks after starting study
      medication. Patients received the Alzheimer's Disease Assessment Scale--Cognitive
      on all five occasions and the Mini-Mental State Examination on three occasions
      (baseline, week 6, and week 12). Their primary caregivers completed the
      Progressive Deterioration Scale on all five visits. This self-administered
      questionnaire consists of 29 items regarding the patient's behavioral and
      functional status. The extrapolated yearly rate of change of the mental status
      examinations was considerably smaller than expected compared with uncontrolled
      natural history studies. In addition, there was a large within-subject
      variability on all three measures. Scores from the baseline assessments
      contributed more to the variability than did the later assessments. The small
      magnitude of change, as well as the large between-subjects and within-subject
      variability, points out the methodologic drawbacks of short-duration therapeutic
      trials in patients with AD and the challenges in demonstrating reliable treatment
      effects for potential therapeutic agents.

PMID- 8309571
TI  - Olfactory function in Parkinson's disease subtypes.
AB  - Decreased olfactory function commonly occurs in idiopathic Parkinson's disease
      (PD), regardless of stage, treatment, or duration of disease. In the present
      study, we sought to determine whether different subtypes of PD, categorized
      according to well-defined clinical criteria, evidence different degrees of
      olfactory dysfunction. Significantly different scores on the University of
      Pennsylvania Smell Identification Test (UPSIT) were present between patients with
      benign PD and malignant PD (respective means [SD] = 22.51 [8.50] and 17.38
      [6.29]) and between tremor-predominant PD and postural instability-gait disorder
      (PIGD)-predominant PD (23.43 [8.18] versus 17.35 [6.00]). No statistically
      significant differences in UPSIT scores were observed between young-onset and
      older-onset PD patients. Women outperformed men in most subtypes examined.

PMID- 8309572
TI  - Speech localization using repetitive transcranial magnetic stimulation.
AB  - To evaluate whether repetitive transcranial magnetic stimulation (RTMS) may be
      used for speech localization, we compared the results from RTMS with the
      intracarotid amobarbital test (IAT) in 21 patients undergoing surgical treatment
      (amygdalohippocampectomy or anterior temporal lobe resection) for medically
      intractable partial epilepsy. None of the patients had aphasia. We stimulated the
      temporal and frontal cortex on each side at a frequency of 30 Hz for 1 second and
      increased the intensity until speech was inhibited. A list of words and forward
      and backward counting were used to test speech function. The IAT was performed on
      the hemisphere of proposed surgery by unilateral injection and simultaneous
      regional cerebral blood flow (rCBF) recordings. In one patient, there was doubt
      about hemisphere dominance and a second bilateral IAT was performed. Fifteen
      patients had left-sided speech dominance; one, left-sided dominance and a
      moderate right-sided speech inhibition; two, right-sided speech dominance; and
      one, bilateral speech representations (bilateral injection at the IAT) with both
      techniques. One patient showed bilateral with right-sided speech dominance by
      RTMS and showed right-sided speech inhibition with right-sided injection only at
      the IAT procedure. One patient differed from the rest, showing bilateral
      representations with right-sided speech dominance with RTMS and left-sided speech
      inhibition by IAT with left-sided injection only. The concordance was 95%. None
      of the patients had seizures provoked by the procedure. We conclude that speech
      localization with RTMS shows a high concordance with the results from the IAT and
      may be useful in addition to traditional techniques in speech
      localization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309573
TI  - Motion perception in optic neuropathy.
AB  - We tested motion perception in 15 eyes of 13 patients with optic neuropathy.
      Eleven of the eyes had optic neuritis. The motion perception paradigm tested
      subjects' ability to discriminate the direction of a global coherent motion
      signal amid varying levels of background noise. The results showed defective
      motion processing in eight of the 15 eyes. This defect was not due to low
      visibility (poor spatial resolution), since 11 of the 15 eyes had Snellen
      acuities of 20/20 or better. Neither was impaired motion perception due to
      decreased luminance sensitivity, since attenuating the display signal by 2.1 log
      units (0.6 units more than the worst relative afferent pupillary defect in any
      patient) in five normal eyes had no effect. Motion perception and critical
      flicker fusion were independent of each other. Given proposals that both depend
      exclusively on the same M, or transient, channel, we had not predicted this
      double dissociation between flicker and motion perception.

PMID- 8309574
TI  - Pathologic findings in a case of primary progressive aphasia.
AB  - We report the histopathologic and immunohistochemical findings of a patient who
      suffered from primary progressive aphasia for 13 years. During the course of his
      illness, he was diagnosed as having Pick's disease, based on gradually
      progressive mild personality changes and MRI findings of severe bilateral
      temporal lobe atrophy. There was severe neuronal loss in the temporal gyri,
      intense gliosis throughout the cortex, and mild gliosis of the temporal white
      matter, without any changes typical for Alzheimer's disease or Pick's disease.
      Using the antibody Alz-50, we found many Alz-50-positive neurons that exhibited a
      granular or diffuse cytoplasmic stain without fibrous structures in the temporal
      and parietal cortex, but no ubiquitin or beta (A4) protein-reactive cells, nor
      spongiform changes. Staining for Alz-50 and ubiquitin did not reveal the presence
      of Pick bodies or Lewy bodies. We consider this case to be an example of
      nonspecific cortical degeneration. Our findings stress the need for
      histopathologic verification of the primary progressive aphasia syndrome.

PMID- 8309575
TI  - A study of idiopathic torsion dystonia in a non-Jewish family: evidence for
      genetic heterogeneity.
AB  - A gene (DYT1) for idiopathic torsion dystonia (ITD) was mapped to chromosome 9q34
      in non-Jewish and Jewish families; the dystonia in these families usually began
      in childhood, with the limb muscles affected first. The role of the DYT1 gene in
      adult-onset and cervical- or cranial-onset ITD is unknown. We examined 53
      individuals from four generations of a non-Jewish North American family with
      adult-onset ITD. There were seven affected family members, with a mean age at
      onset of 28.4 years (range, 7 to 50 years). In six of the seven, the neck was
      affected first. All seven developed cervical dystonia, and dysarthria or
      dysphonia occurred in five. Linkage data excluded the region containing the DYT1
      locus, indicating that DYT1 was not responsible for ITD in this family. This
      study provides evidence that a gene other than DYT1 is responsible for some cases
      of adult cervical-onset dystonia.

PMID- 8309576
TI  - Cerebrotendinous xanthomatosis: molecular diagnosis enables presymptomatic
      detection of a treatable disease.
AB  - We report an early molecular diagnosis of cerebrotendinous xanthomatosis (CTX) in
      a Jewish Moroccan family with two affected siblings. The proband displayed
      characteristic manifestations of the disease, whereas a younger brother,
      homozygous for the mutant allele, was asymptomatic. Clinical studies in the
      younger patient disclosed mild cognitive impairment, peripheral neuropathy, and
      abnormal EEG. Elevated plasma cholestanol levels were evident in both affected
      patients, with documented normal levels in the molecularly diagnosed heterozygous
      family members. Molecular characterization of affected CTX families provides
      early diagnosis and treatment of homozygotes in the presymptomatic state as well
      as identification of heterozygotes, which is crucial for genetic counseling and
      for prenatal diagnosis.

PMID- 8309577
TI  - Iatrogenic Creutzfeldt-Jakob disease: an example of the interplay between ancient
      genes and modern medicine.
AB  - We tested DNA from 15 centrally infected cases of iatrogenic Creutzfeldt-Jakob
      disease (CJD) (dura mater or corneal homografts and stereotactic EEG electrodes),
      11 peripherally infected cases (native human growth hormone or gonadotrophin),
      and 110 control individuals for the presence of mutations in the chromosome 20
      amyloid gene. No patient or control had any of the known pathogenic point or
      insert mutations found in familial disease, but allelic homozygosity at
      polymorphic codon 129 was present in all but two (92%) of the 26 patients,
      compared with 54 (50%) of the 110 controls (p < 0.001). Pooled data from all
      identified and tested cases of iatrogenic disease yielded a worldwide total of 56
      patients, of whom all but four were homozygous at codon 129 (p < 0.001). These
      findings support the thesis that homozygosity at codon 129 enhances
      susceptibility to iatrogenic infections of both central and peripheral origin,
      with evident implications for the population of dura mater homograft and
      pituitary hormone recipients whose lives have been complicated by the possibility
      of exposure to the infectious agent of CJD.

PMID- 8309578
TI  - Improvement of left unilateral spatial neglect in a line extension task.
AB  - Patients with left unilateral spatial neglect following lesions that mainly
      involved the right parietal lobe performed a line extension task, extending a
      horizontal line leftward to double its original length. We examined line
      extension performances in the left and right hemispaces, as well as in the
      midline, to assess whether spatial conditions affected these performances.
      Whatever the severity of neglect found in the line bisection test, the line
      extension performances of the patients were almost accurate and comparable with
      those of normal controls across the three spatial conditions. The neglect
      patients executed movements in or toward the contralesional space as the task
      oriented their attention sufficiently to the left. The results suggest that the
      motor component, ie, directional hypokinesia, has little part in left unilateral
      spatial neglect due to right parietal lesions.

PMID- 8309579
TI  - Left hemispheric neuronal heterotopia: a PET, MRI, EEG, and neuropsychological
      investigation of a university student.
AB  - A 21-year-old left-handed medical student had a prominent unilateral cerebral
      cortical malformation due to an ontogenetic migration disorder. We performed
      neuropsychological studies, EEG, T1- and T2-weighted and proton-density MRI, and
      positron emission tomography (PET) (under both the resting condition and
      neuropsychological activation). Neuropsychological testing revealed normal
      intelligence and generally normal memory functioning but selective deficits in
      tests of verbal fluency and spatial-figural relationships. Proton-density and T2
      weighted MRI revealed extensive left cortical heterotopia that included parts of
      the Wernicke area. PET under the resting condition revealed a small
      interhemispheric difference with slightly reduced glucose metabolism in the left
      temporoparietal cortical zone. An activation PET (with the patient performing a
      verbal fluency test) resulted in a normal overall increase in metabolism but
      marked deviations in cortical areas. The highest activity changes were in the
      Broca and Wernicke areas of the right hemisphere, and there was very little
      activation in those regions of the left hemisphere that were expected to respond
      well to the activation--the temporal, parietal, and temporo-occipital cortical
      zones. We conclude that there can be large compensations for unilateral
      heterotopia.

PMID- 8309580
TI  - Altered pulsatile secretion of luteinizing hormone in women with epilepsy.
AB  - Menstrual disorders and infertility are common among women with epilepsy of
      temporal lobe origin (TLE). Reproductive endocrine disorders may be the cause.
      Polycystic ovarian syndrome (PCO) and hypothalamic amenorrhea (hypogonadotropic
      hypogonadism, HH), in particular, are significantly overrepresented and
      attributable to hypothalamic dysfunction. We therefore compared the hypothalamic
      function of 14 women with clinically and electrographically documented TLE with
      that of eight age-matched normal controls by determining the interictal pulse
      frequency and amplitude of luteinizing hormone (LH) secretion. Serum for LH
      measurement was drawn every 15 minutes from 8 AM to 4 PM in both groups. LH pulse
      frequency values were significantly more variable (p < 0.05) and lower (p < 0.05)
      among women with TLE than among controls. Women with left temporal EEG foci
      showed a trend toward higher pulse frequencies compared to women with right foci
      (p = 0.05 to 0.10). Among five women with reproductive endocrine disorders, the
      three with PCO had left-sided foci and average LH pulse frequency two times
      higher than that of the two women with HH, who had right-sided foci. Eight
      reproductively normal, medically treated women with TLE had significantly lower
      LH pulse frequencies than did the one reproductively normal, untreated woman with
      TLE (p < 0.05) and the eight normal controls (p < 0.001). These findings suggest
      that LH pulse frequencies in women with TLE may be influenced by the laterality
      of the epileptic focus, the reproductive endocrine status, and the use of
      antiseizure medications.

PMID- 8309581
TI  - Longitudinal study of frequency of HPRT mutant T cells in patients with multiple
      sclerosis.
AB  - Analysis of somatic mutation in circulating peripheral blood T cells can be used
      as an index of in vivo T-cell amplification. The ability to assess the frequency
      of T cells that survive in vitro in the presence of 6-thioguanine is an index of
      mutation at the HPRT gene locus. In the absence of exposure to mutational agents,
      elevations of the HPRT mutant frequency (mF) of T cells reflects errors in DNA
      replication and repair that have become fixed during the process of cell
      division. We estimated the mF of T cells in MS patients and controls over a
      period of 36 months and found that the mF was consistently elevated in MS
      patients of all clinical subgroups. In the chronic progressive group of MS, the
      mF increased over a 3-year period and appeared to correlate with the clinical
      worsening of the disease.

PMID- 8309582
TI  - Familial carpal tunnel syndrome due to amyloidogenic transthyretin His 114
      variant.
AB  - We studied two patients from a Japanese family with carpal tunnel syndrome (CTS).
      The biopsy samples obtained during CTS surgical release revealed deposits of
      amyloid that stained with antihuman transthyretin (TTR) antiserum. Single-strand
      conformation polymorphism analysis and sequence analysis of polymerase chain
      reaction (PCR)-amplified exons of the proband's TTR gene revealed a point
      mutation resulting in a substitution of histidine for tyrosine at position 114.
      The mutation was confirmed by PCR-primer-induced restriction analysis. Our
      findings account for clinical heterogeneity of TTR-derived amyloidosis, and
      suggest the importance of substitution itself for deposits of amyloid in CTS.

PMID- 8309583
TI  - Impaired simultaneous cognitive task performance in Parkinson's disease: a
      dopamine-related dysfunction.
AB  - Patients with Parkinson's disease (PD) have trouble programming two separate
      motor acts concurrently. We tested the hypotheses that (1) PD patients may also
      have difficulty processing two cognitive tasks simultaneously, and (2) the
      expected deficit may be related to the striatal dopaminergic depletion. We used
      auditory and visual choice reaction time (CRT) tasks, presented either separately
      or concurrently, and compared the performance of three groups of PD patients: a
      group of patients under their usual dose of levodopa ("standard"); a group
      assessed both at the time of maximal clinical benefit ("on" state) and at the
      time of minimal clinical benefit (treatment withdrawn for about 18 hours; "off"
      state); and a group of recently diagnosed untreated patients ("de novo").
      Compared with controls, standard and "on" state patients had a normal performance
      for both separate and concurrent CRT tasks. In contrast, "off" state and de novo
      patients had a normal performance in the separate CRT tasks but significant
      deficits in the concurrent CRT tasks. These results suggest that adequate
      dopaminergic transmission is necessary for concurrent processing of cognitive
      information and that the striatum integrates the sensorimotor information
      required to program cognitive acts.

PMID- 8309584
TI  - Magnetic resonance evaluation of disease activity during pregnancy in multiple
      sclerosis.
AB  - We followed two women with MS during pregnancy by means of serial unenhanced MR
      imaging. On each follow-up image, we assessed the number of new or enlarging
      lesions. Both women showed a decrease in MR disease activity during the second
      half of pregnancy and a return of MR disease activity to prepregnancy levels in
      the first months postpartum. These findings support the view that pregnancy
      reduces disease activity in MS.

PMID- 8309585
TI  - A genetic marker and family history study of the upstate New York multiple
      sclerosis cluster.
AB  - We report nine additional cases of new-onset multiple sclerosis (MS) among
      employees of an upstate New York manufacturing plant that uses zinc as a primary
      metal. These cases, identified during the decade 1980 to 1989, had clinical onset
      of the disease between 1979 and 1987. The new cases confirm the increased
      incidence of MS previously reported in the plant population for the 1970 to 1979
      decade. The MS subjects in this occupationally based cluster do not seem
      different from other MS patients with regard to rates of familial MS or the
      frequencies of alleles for human leukocyte (HLA-DR) antigens or transferrin. The
      frequency distribution of alleles for transferrin (an iron- and zinc-binding
      protein) may differ in these and other MS subjects compared with controls.

PMID- 8309586
TI  - Heterogeneity of calcium channel autoantibodies detected using a small-cell lung
      cancer line derived from a Lambert-Eaton myasthenic syndrome patient.
AB  - We investigated the heterogeneity of anti-voltage-gated calcium channel (VGCC)
      antibodies in the Lambert-Eaton myasthenic syndrome (LEMS) using a small-cell
      lung carcinoma line (MB) derived from an LEMS patient. Four of 13 LEMS patients
      had raised titers of anti-125I-omega-conotoxin-labeled (N-type) VGCCs, measured
      by radioimmunoassay using line MB as the source of antigen. Antagonists for L
      type (nitrendipine and nifedipine) and N-type (omega-conotoxin) VGCCs inhibited
      K(+)-stimulated (voltage-dependent) Ca2+ flux into this line--by 22% for L-type
      and 2% for N-type at maximum concentration. Inhibition by the LEMS IgGs, by
      contrast, ranged from 46 to 78% at a concentration of 2 mg/ml. These differing
      effects on Ca2+ flux inhibition by LEMS IgGs on the one hand and by L- and N-type
      channel antagonists on the other, taken together with the observation that many
      of the sera failed to react with omega-conotoxin-labeled (N-type) channels in the
      immunoprecipitation assay, suggest that in many LEMS patients the autoantibodies
      target other VGCC subtypes besides L- or N-types, and that these are important in
      inducing the myasthenic disorder.

PMID- 8309587
TI  - ApoE epsilon 4 allelic association with Alzheimer's disease: independent
      confirmation using denaturing gradient gel electrophoresis.
AB  - There is intriguing evidence associating apolipoprotein E (ApoE) with Alzheimer's
      disease (AD). ApoE is deposited with beta-amyloid in senile plaques and binds to
      beta-amyloid in vitro. We used denaturing gradient gel electrophoresis to
      identify ApoE epsilon 2, epsilon 3, and epsilon 4 alleles in 135 control subjects
      and 57 AD patients. We observed a marked increase in ApoE epsilon 4 allele
      frequency (0.40) in AD patients compared with control subjects (0.14) (p <
      0.0001). Our independent finding of a marked association of ApoE epsilon 4 allele
      with AD further supports a possible role of ApoE in the pathogenesis of AD and
      confirms the study of Saunders et al (Neurology 1993;43:1467-1472).

PMID- 8309588
TI  - Confirmation of the epsilon 4 allele of the apolipoprotein E gene as a risk
      factor for late-onset Alzheimer's disease.
AB  - Family studies indicate a possible linkage between the q13.2 region of chromosome
      19 and Alzheimer's disease (AD). An isoform of apolipoprotein E, whose gene maps
      in this region, is more frequent in AD. In this study, we investigated the
      possible association of a genetic polymorphism of the apolipoprotein E gene with
      late-onset AD. We compared apolipoprotein E polymorphism distribution between
      patients with sporadic late-onset AD (n = 36) and controls of the same age (n =
      38). Individuals carrying at least one epsilon 4 allele were present in 41.7% of
      the patients, compared with only 10.5% of the controls (p < 0.001). This result
      indicates an association between late-onset AD and the 19q13.2 region containing
      the apolipoprotein E gene locus.

PMID- 8309589
TI  - Intermittent encephalopathy, reversible nerve conduction slowing, and MRI
      evidence of cerebral white matter disease in methylenetetrahydrofolate reductase
      deficiency.
AB  - We describe a patient with methylenetetrahydrofolate reductase (MTHFR) deficiency
      in whom clinical and electrophysiologic fluctuations paralleled exacerbations of
      hyperhomocyst(e)inemia. MRI demonstrated abnormalities characteristic of a
      leukodystrophy.

PMID- 8309591
TI  - The "Schaltenbrand experiment," Wurzburg, 1940: scientific, historical, and
      ethical perspectives.

PMID- 8309590
TI  - SOD1 missense mutation in an Italian family with ALS.
AB  - We have discovered a new Italian pedigree with autosomal-dominant ALS. The
      pedigree, at present, comprises 75 members distributed in five generations. ALS
      was diagnosed in eight patients. The mean +/- SD age of onset of the disease was
      46.8 +/- 13.5 years, with a range of 29 to 63 years. The mean +/- SD duration of
      the disease was 11.6 +/- 1.7 months. Molecular genetic studies showed a missense
      mutation (Gly-->Ser, codon 41) in exon 2 of the Cu/Zn superoxide dismutase gene
      (SOD1) on chromosome 21 in the available affected member and in 45% of the at
      risk subjects of the pedigree. This study confirms the presence of SOD1 point
      mutations in families with autosomal-dominant ALS and suggests that additional
      genetic or environmental factors may be involved in the full expression of the
      disease.

PMID- 8309592
TI  - Diabetes insipidus as first manifestation of primary central nervous system
      lymphoma.

PMID- 8309593
TI  - Fisher's syndrome.

PMID- 8309594
TI  - HIV or zidovudine myopathy?

PMID- 8309595
TI  - HIV or zidovudine myopathy?

PMID- 8309596
TI  - HIV or zidovudine myopathy?

PMID- 8309597
TI  - HIV or zidovudine myopathy?

PMID- 8309598
TI  - Levodopa pharmacodynamics.

PMID- 8309599
TI  - 'Locked-in' patients.

PMID- 8309600
TI  - [Laparoscopic cholecystectomy. Our experience].
AB  - This study analysed 90 cases of symptomatic cholelithiasis treated with
      laparoscopic cholecystectomy. 27% of the cases studied suffered from
      microlithiasis, 44% from multiple calculosis with calculi measuring 1 to 2 cm in
      diameter, 25% from single calculi measuring up to 4 cm in diameter, and 4% from a
      benign proliferative pathology of the cholecystic wall. Calculosis of the main
      biliary tract was also found in 3 patients and was treated by preoperative
      endoscopic papillosphincterotomy. In addition to routine tests and
      ultrasonography, endovenous cholangiography, or retrograde cholangiography (ERCP)
      in cases of suspected calculosis of the biliary tract, was always performed prior
      to surgery. Mean operating time was 60 min. Two procedures were converted into
      laparotomy due to laceration of the cystic artery. In one case laparotomy was
      performed on day two due to choleperitoneum following a lesion of the cystic
      duct. Pneumoperitoneum could not be performed in three cases. Mean hospital stay
      was 48 hours. No other intra- or postoperative complications were reported. These
      results support the opinion that laparoscopic cholecystectomy is a safe method,
      with few limitations and represents the treatment of choice in the therapy of
      symptomatic cholelithiasis.

PMID- 8309602
TI  - [Indications for the surgical treatment of esophageal varices hemorrhage].
AB  - The authors present their experience in the treatment of acute bleeding from
      oesophageal varices. From 1983 to 1991, 596 patients underwent sclerotherapy
      during diagnostic endoscopy; a stop to bleeding was achieved in 512 cases (86%).
      Twenty-seven surgical emergency decompressive shunts were performed, 14 total
      portal-systemic and 13 selective; operative mortality was 64% and 54%
      respectively. One patient was submitted to oesophageal-gastric devascularization.
      Hundred-sixty elective shunts were performed, 99 total portal-systemic and 61
      selective; operative mortality was 8% and 11% respectively. Since 1990 3 patients
      received liver transplantation. The 5-year survival rate of patients submitted to
      selective shunts was 46%; the 5-year survival rate of nonalcoholic cirrhotics
      submitted to shunt SRD was 73%.

PMID- 8309601
TI  - [Videolaparoscopic cholecystectomy. Experience, evolution, and comparison of
      techniques].
AB  - The paper broadly outlines the technique of laparoscopic cholecystectomy used by
      the authors to treat patients suffering from calculosis of the gallbladder.
      Basing their comments on the French school, the authors review the literature to
      identify those innovations introduced by individual operators in elation to the
      original technique which have enabled this method to be extended to those cases
      complicated by acute cholecystitis, VBP calculosis or sequelae from abdominal
      surgery. The most important innovations include the use of a laparoscope with
      oblique 30-degrees vision, which is extremely useful during the dissection of
      Calot's triangle since it allows VBP to be identified with greater ease and
      precision, above all in the event of phlogistic sequelae enclosing the peduncle.
      In addition, laparoscopic suture or ligation using Roeder's running-knot, used by
      the Dundee school to treat the cystic duct and artery, presents considerable
      advantages compared to the conventional use of metal clips. The authors also
      emphasise the growing return to intraoperative cholangiography which is routinely
      performed by some authors and is of value in identifying anatomic anomalies,
      iatrogenic lesions and VBP calculi unnoticed by preoperative tests. A second
      innovation which is highlighted consists of the treatment of choledocholithiasis
      during the course of laparoscopic cholecystectomy, in addition to pre- and
      postoperative endoscopic papillo-sphincterotomy.

PMID- 8309603
TI  - [Surgical therapy of obstructive tumors of the large intestine].
AB  - Current option in managing obstructive colorectal carcinoma is a one stage
      procedure. Between 1987 and 1991, 47 cases of obstructive colorectal cancer were
      managed. A statistical analysis showed no significant difference in mortality,
      morbidity and hospital stay when comparing elective and emergency one staged
      resection and reconstruction.

PMID- 8309604
TI  - [Primary lymphoma of the small intestine].
AB  - Lymphomas of the small bowel are rare tumors with few characteristics. Clinical
      and radiological diagnosis is difficult, because they may be confused by
      inflammatory or neoplastic forms, especially in primary involvement of the small
      intestine. Observation of three cases of primary extranodal lymphomas of the
      small bowel prompted a review of problems relating to the histology, clinical
      manifestations and the staging classification. This system is an important aid in
      the evaluation of the treatment and prognosis of these forms.

PMID- 8309605
TI  - [Biliary lithiasis and carcinoma of the gallbladder].
AB  - Gallstones are a major risk factor for gallbladder cancer, but only few patients
      with stone experience develop this tumor. To examine this relationship, twenty
      one patients with gallbladder cancer referred to our Institute over a 26-year
      period were studied. The tumor was most common in older females (95.2%) (median
      age 69.2 years). Seventy-six percent of patients had gallstones. The cell type in
      57.1% of patients was adenocarcinoma. The prognosis is poor, the median survival
      time was 6.7 months.

PMID- 8309606
TI  - [Prophylaxis of postoperative infections: immunoglobulins or antibiotics?].
AB  - Authors report the preliminary results of their experience in the infections
      prophylaxis treatment on the operated oncologic patient, with a particular care
      for immunoprophylaxis aiming to improve the immune defenses. 89 patients have
      been considered, dividing them into three groups according to the therapy carried
      out: e.v. immunoglobulins (300 mg/kg per day, for three days), e.v.
      immunoglobulins associated with routine antibiotic prophylaxis, routine
      antibiotic prophylaxis. The results show a remarkable reduction both of the
      period of postoperative bedridding in the group treated with e.v. immunoglobulins
      only, and of the infective complications in the patients treated with e.v.
      immunoglobulins (alone or in association with antibiotic prophylaxis), compared
      with the check group (antibiotic prophylaxis only).

PMID- 8309607
TI  - [Upper digestive hemorrhage. Comparison of terlipressin and octreotide].
AB  - The efficacy and tolerability of both Terlipressin and Octreotide in the
      treatment of upper digestive haemorrhage (oesophagus, stomach and duodenum) have
      been compared, at random, on 30 adult patients. Terlipressin dosage was 2 mg/4
      hours i.v. during the first 24 hours, 2 mg/6 hours during the following 24 hours.
      Octreotide dosage was 50 micrograms i.v. and infusional therapy, 25
      micrograms/hours, followed. Haemostasis was obtained in 100% of patients treated
      with Terlipressin and in 73% of patients treated with Octreotide. Rebleeding
      occurred in 3 patients treated with Terlipressin and 4 patients treated with
      Octreotide. Side effects occurred in 4 patients treated with Terlipressin and 8
      patients treated with Octreotide. Terlipressin proved to have a better efficacy
      in comparison with Octreotide, and had less side effects.

PMID- 8309608
TI  - [Treatment of inguinal hernia in local anesthesia: our experience with the
      Shouldice surgical technique].
AB  - The authors present their personal experience in the surgical treatment of 256
      cases of patients suffering from inguinal hernia, using the Shouldice technique
      in local anaesthesia. Minor incidence intra and postoperative complications
      compared with other types of anaesthesia, the possibility to converse with the
      patient during the operation and if necessary to invite him to cough in order to
      exclude the presence of other associated hernias or to assay the robustness and
      the resistance of the plastic, minor frequency of relapses compared with other
      operating techniques (1.5% in the Shouldice against 3% of the Bassini), and last
      but not least the possibility of early discharge from hospital and more swift
      resumption of work, confirm the full validity of this hernial plastic surgery.

PMID- 8309609
TI  - [Local anesthesia in anal surgery. Technical note and immediate results].
AB  - The authors report their experience with the use of local anesthesia in anal
      surgery (hemorrhoids, anal fissures and fistulas). They describe their technique
      in detail, stressing the importance of thorough knowledge of the neuroanatomy of
      the anal canal and of a stepwise blockage of all sensory and motor fibers to the
      area. They report their results on 300 anal procedures performed under local
      anesthesia, with good patient acceptance.

PMID- 8309610
TI  - [Iatrogenic esophago-tracheal fistula treated with endoscopically administered
      fibrin glue].
AB  - Successful closure of a iatrogenic tracheoesophageal fistula by means of
      bronchoscopic application of fibrin glue in a 77-year old patient is reported.
      The fistula was completely obliterated after a single application of the glue,
      with resolution of the clinical and radiological signs. The procedure may be
      suggested as an alternative to surgery or as first attempt before surgery in very
      selected patients with TEF.

PMID- 8309611
TI  - [Myomatous tumor of the stomach. 3 clinical cases].
AB  - Three cases of smooth muscle tumors of the stomach are reported: a leiomyoma, a
      leiomyosarcoma and a leiomyoblastoma observed over a period of five years.
      Clinical presentation, diagnostic procedure and surgical treatment are discussed
      and the literature is reviewed.

PMID- 8309612
TI  - [Bouveret's syndrome: unusual variety of biliary ileum].
AB  - The authors report one case of Bouveret's syndrome that come to their
      observation. Physiopathology, clinic and diagnosis are discussed. After the
      method of stone removal they emphasized the surgical procedure in one stage with
      enterotomy and stone-removal, cholecystectomy and repair of biliary fistula.

PMID- 8309613
TI  - [Digestive hemorrhage secondary to biliary ileus. Endoscopic diagnosis].
AB  - A rare case of gastrointestinal hemorrhage is presented. The cause of bleeding
      was ulcer of the descending duodenum due to erosion of an impacted gallstone.
      Oral endoscopy made possible a preoperative diagnosis and, pushing the gallstone,
      made surgery easier. The patient underwent enterolithotomy and had a completely
      uneventful course.

PMID- 8309614
TI  - [Splenectomy for splenic abscess caused by Salmonella typhi].
AB  - Splenectomy due to splenic abscess is without doubt an unusual occurrence,
      especially in Western countries. The paper reports the case of 19-year-old male
      who underwent splenectomy because of an abscess caused by Salmonella typhi.
      Following a revision of the literature it appears that only six cases of splenic
      abscess by S. typhi have been reported since 1940. Splenectomy represents the
      elective treatment for patients with splenic abscess provoked by any cause.

PMID- 8309615
TI  - [Subacute Budd-Chiari syndrome treated with rTPA. Considerations on a case].
AB  - The authors report on a case of hepatic vein thrombosis or Budd-Chiari syndrome
      (BCS) successfully treated with recombinant Tissue Plasminogen Activator (rTPA).
      They briefly outline the etiology and symptomatology of this disease as well as
      the various surgical procedures used for treatment. Medical therapy has been so
      far poorly effective in treatment BCS, but recently various reports seem to
      indicate that rTPA may have a role. The authors suggest that rTPA may be used as
      the only therapy in selected cases, or in treating patients that are not
      candidates for surgical intervention, or as a temporizing measure to improve
      symptoms in patients awaiting surgery.

PMID- 8309616
TI  - Chronic morphine alters dopamine transporter density in the rat brain: possible
      role in the mechanism of drug addiction.
AB  - The effect of acute or chronic morphine treatment on dopamine transporters was
      studied with the selective transporter blocker [3H]GBR12935. Chronic, but not
      acute treatment of rats with morphine significantly decreased the Bmax of
      [3H]GBR12935 binding to membranes from the anterior basal forebrain, that
      includes the nucleus accumbens, but had no such effect on binding to striatum
      membranes. No effect on the affinity (Kd) of the radioligand to either one of the
      two brain regions was observed. The selectivity of morphine interaction with the
      dopamine system was tested with a ligand that binds selectively to serotonin
      transporters, [3H]citalopram. Neither acute nor chronic morphine altered
      [3H]citalopram binding to the anterior basal forebrain, or the striatum
      membranes. It is suggested, therefore, that chronic morphine treatment has a long
      lasting and selective effect on the activity of dopamine transporters in the
      dopaminergic reward pathway, but not in the striatum.

PMID- 8309617
TI  - Affinity of 1-aminoadamantanes for the sigma binding site in post-mortem human
      frontal cortex.
AB  - The 1-aminoadamantanes memantine (1-amino-3,5-dimethyl-adamantane) and amantadine
      (1-amino-adamantane) are clinically used as anti-parkinsonian, anti-spasticity,
      anti-dementia and antiviral drugs. In the present investigation we have tested a
      series of 1-aminoadamantane derivatives including memantine and amantadine for
      their ability to compete with [3H](+)-pentazocine in homogenates of post-mortem
      human frontal cortex. The Ki values ranged from 0.237 +/- 0.019 microM for 1-N
      dimethyl-amino-3,5-dimethyl-adamantane to 20.25 +/- 16.48 microM for amantadine.
      The Ki value of memantine was 19.98 +/- 3.08 microM and was thus very similar to
      that of amantadine. Memantine, at therapeutic concentrations, probably does not
      interact with the sigma binding site. Amantadine, at therapeutic concentrations,
      probably binds both to the sigma site and to the phencyclidine (PCP) binding site
      of the N-methyl-D-aspartate (NMDA) receptor.

PMID- 8309618
TI  - Prior ischemic stress protects against experimental stroke.
AB  - We studied the possible role of prior ischemic stress as a protective mechanism
      against cerebral infarction in rats. Two brief periods of global cerebral
      ischemia, separated by 24 h, did not cause cell death in brain, but did produce
      neuronal stress, as demonstrated by induction of the nonconstitutive 72 kDa heat
      shock protein (HSP72). Forty-eight hours later, animals subjected to prior
      ischemia had smaller infarct from permanent middle cerebral artery occlusion than
      did sham-operated controls. These findings support an association between
      ischemia-induced stress, HSP72 induction, and attenuation of injury from
      subsequent focal cerebral ischemia.

PMID- 8309619
TI  - Intracellular ATP changes the voltage-dependence of delayed rectifier potassium
      current in bullfrog primary afferent neurons.
AB  - Dissociated bullfrog dorsal root ganglion cells were voltage-clamped in the whole
      cell configuration to study the steady-state activation and inactivation curves
      for a delayed rectifier potassium current. The 50%-activation of the current
      occurred at +15 mV when measured with ATP (5 mM) in the pipette solution as
      opposed to -11 mV with 5'-adenylylimidodiphosphate (AMP-PNP, 5 mM) and -15 mV
      with adenosine 5'-O-(3-thiotriphosphate) (5 mM). The 50%-inactivation of the
      current occurred at -6 mV with ATP but at -31 mM with AMP-PNP. The results
      suggest that intracellular ATP modulates voltage-dependence of the delayed
      rectifier in amphibian afferent neurons.

PMID- 8309620
TI  - A study of GABAergic system in Scrapie-infected hamsters after striatal
      microinoculation of the agent.
AB  - Experimental Scrapie in hamster is a simple, reproducible model of prion diseases
      that occur in humans and animals. Stereotaxic microinoculation (0.5 microliter)
      of the agent (263 K) into a specific cerebral structure (striatum) in hamster,
      previously developed in our group, gives the opportunity to further investigate
      the pathogenesis of these degenerative diseases and to more precisely define the
      brain areas and the groups of cells more vulnerable to the effects of the agent.
      In this model, early significant changes of glutamic acid decarboxylase (GAD)
      activity in striatum suggested a preferential alteration of the GABA system. The
      present study was focused on the effects of Scrapie agent directly injected into
      striatum on GABA neurons at the presynaptic level (GABA uptake) and at the
      postsynaptic level (GABAA receptors). The high-affinity [3H]GABA uptake is not
      changed in the Scrapie-injected striatum neither in the controlateral site and
      the kinetics (Km, Vmax) values are not statistically different for control and
      Scrapie-inoculated animals. The binding of [3H]GABA (Scatchard analysis) to
      cerebral membranes does not seem to be altered either at the local site of agent
      inoculation (striatum) neither at distance in the cerebellum: the affinity
      constant (Kd) to the ligand and the maximal number of receptor sites were of the
      same magnitude in control and Scrapie animals, but we do not have a statistical
      analysis. These effects are completely different of those of a neurotoxin. The
      present data suggest that the effects of prion agent may be very limited and very
      specific to some cellular mechanisms, without altering the whole cellular
      machinery, as recently shown in an in vitro model.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8309621
TI  - Electrophysiological evidence for the presence of receptors for cholecystokinin
      and bombesin on cultured astrocytes of rat central nervous system.
AB  - The action of cholecystokinin (CCK) and bombesin (Bom) was studied on the
      membrane potential of astrocytes in explant cultures of rat cortex, cerebellum,
      brain stem and spinal cord. Both peptides (10(-8) and 10(-7) M) caused a
      hyperpolarization of most astrocytes studied. The hyperpolarization by CCK was
      markedly reduced or blocked by the CCKB-antagonist L-365,260 whereas addition of
      the Bom-antagonist [D-Phe12,Leu14]-Bom antagonized the effects of Bom, suggesting
      a specific action of these peptides. When CCK and Bom were tested on the same
      cell, both peptides were effective, indicating a colocalization of receptors for
      CCK and Bom on the glial membrane. Our electrophysiological investigations
      provide strong evidence for the existence of functional CCK and Bom receptors on
      astrocytes.

PMID- 8309622
TI  - A paradox after systemic kainate injection in rats: lesser damage of hippocampal
      CA1 neurons after higher doses.
AB  - The pyramidal neuron loss in dorsal rat hippocampus was determined 4 days after
      i.p. administration of 10 or 20 mg/kg kainic acid (KA). Histological examination
      revealed that subtotal-to-total loss of the pyramidal neurons in both the CA3 and
      CA1 regions of hippocampus was produced after 10 mg/kg KA. At the higher dose,
      severe damage was evident in the CA3 region while no or only sporadic damage was
      observed in the CA1 region. These findings suggest that the high KA dose damaged
      the CA3 pyramidal neurons before excitatory input through the Schaffer
      collaterals produced irreversible damage to the CA1 pyramidal neurons.

PMID- 8309623
TI  - Effects of 2-mercaptoethanol on survival and differentiation of fetal mouse brain
      neurons cultured in vitro.
AB  - Effects of 2-mercaptoethanol on primary cultures of fetal mouse brain neurons
      have been investigated. The addition of 2-mercaptoethanol to the culture medium
      increased 6- or 200-fold the survival rates of embryonic day-16 murine striatum
      neurons and day-18 cerebral cortical neurons cultured in serum-free medium,
      respectively, and also induced neurite outgrowth, particularly being prominent in
      cortical neurons. Moreover, this drug enhanced trophic activities of the
      conditioned medium of VR-2g or BIM cells. These findings indicate that 2
      mercaptoethanol can support the viability and differentiation of fetal mouse
      brain neurons.

PMID- 8309624
TI  - Frequency of synchronous oscillations of neuronal activity increases during
      development and is correlated to the number of synapses in cultured cortical
      neuron networks.
AB  - It has been proposed that synchronous oscillations of groups of neurons
      corresponding to sensory information and changes in temporal pattern of
      oscillations are important for processing of the information in the cortex.
      However, it has not been determined yet how the temporal or spatial pattern of
      such oscillations are regulated. We observed spontaneous synchronous oscillations
      of Ca2+ transients, which were caused by bursts of action potentials of neurons,
      even in cultured cortical neurons. The frequency of synchronous Ca2+ oscillations
      increased with development of synapses in cultured neurons and was highly
      correlated to the number of synapses formed in the same culture.

PMID- 8309625
TI  - A high frequency of apolipoprotein E4 isoprotein in Japanese patients with late
      onset nonfamilial Alzheimer's disease.
AB  - Phenotypes of apolipoprotein E (apo E) were determined by the iso-electric
      focusing method in 42 Japanese patients with nonfamilial late-onset Alzheimer's
      disease (AD) and 96 age-matched controls without hyperlipidemia and/or diabetes.
      There was a striking difference in the distribution of apo E phenotypes between
      patients with AD and controls (P < 0.0001). Such a difference was mostly
      attributable to different frequencies of phenotypes E4/3 and E3/3. The apo E4/3
      phenotype was detected in 24 (57.1%) of 42 patients with AD, more than six times
      oftener than in nine (9.4%) of 96 controls. In contrast, apo E3/3, which is the
      most common apo E phenotype in various ethnic groups, was detected in only 15
      (35.7%) patients with AD. These results indicate a strong association between apo
      E4 isoprotein and Japanese late-onset nonfamilial AD, and that apo E4 is a
      possible risk factor for the development of this type of AD.

PMID- 8309626
TI  - Spinal cord blood flow changes during the sleep-wake cycle in rat.
AB  - Regional spinal cord blood flow was measured in rats during the sleep-wake cycle
      with the use of radioactive microspheres. Spinal cord blood flow decreases from
      wakefulness to quiet (synchronized) sleep while increasing in active
      (desynchronized) sleep. Blood-flow changes depend on changes in vascular
      resistance whose mechanisms have yet to be elucidated. Blood-gas tension or mean
      arterial pressure, however, do not play a relevant causal role.

PMID- 8309627
TI  - Photic induction of Fos in the hamster suprachiasmatic nucleus is inhibited by
      baclofen but not by diazepam or bicucullin.
AB  - The present study makes use of the photic induction of Fos in the suprachiasmatic
      nucleus (SCN) to explore the pharmacology of retinal input to this circadian
      pacemaker. Our results demonstrate that the GABAA antagonist bicuculline and the
      benzodiazepine agonist diazepam, both of which prevent light-induced phase
      shifts, do not inhibit photic induction of Fos expression in the hamster SCN. In
      contrast, the GABAB agonist, baclofen, prevents both light-induced phase shifts
      and inhibits photic induction of Fos expression in the SCN. One explanation of
      this difference may be that baclofen acts to prevent photic information from
      reaching the SCN while bicuculline and diazepam act within the SCN at a point
      'downstream' from Fos induction.

PMID- 8309628
TI  - Dorsal root ganglion proteins in Friedreich's ataxia.
AB  - The polypeptide composition of dorsal root ganglia from 8 human controls, 6
      Friedreich's ataxia (FA) patients and 1 patient with diabetic neuropathy was
      studied by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis
      (PAGE). Silver-stained gels demonstrated a decrease in a 40-kDa protein in FA
      patients. This protein appeared to be present in normal amounts in the diabetic
      ganglion, suggesting that this 40-kDa protein deficiency was not simply a
      reflection of reduced neuronal numbers but may be specific for FA.

PMID- 8309629
TI  - Activation of the human hippocampal formation during auditory-verbal long-term
      memory function.
AB  - Clinical data from brain-damaged patients implicates the human hippocampal
      formation in memory function. We tested the hypothesis that long-term memory
      function is associated with activation of the hippocampal formation in humans by
      measuring regional cerebral blood flow changes whilst subjects performed memory
      tasks. Bilateral hippocampal regional cerebral blood flow was significantly
      correlated with a measure of the engagement of long-term auditory-verbal memory.
      No such association was observed for the degree of engagement of auditory-verbal
      subspan memory. These data provide, for the first time, direct in vivo evidence
      for the involvement of the hippocampal formation in long-term memory in the
      intact human brain.

PMID- 8309630
TI  - Circadian regulation of per repeat mRNA in the suprachiasmatic nucleus of rat
      brain.
AB  - We have recently reported fluctuations in the expression of the period repeat
      sequence (pp2.5) during light-dark cycles in the suprachiasmatic nucleus (SCN) of
      rat [Neurosci. Lett., 122 (1991) 113-116]. Presently, we performed in situ
      hybridization which shows that the fluctuation of pp2.5 expression continues
      during constant darkness conditions in the SCN of rat. The light exposure during
      subjective night but not subjective day triggered its elevated expression in a
      time-dependent manner which is parallel to that of c-fos expression. The results
      suggest the involvement of pp2.5 in the entrainment pathway of the circadian
      rhythm in rodent SCN.

PMID- 8309632
TI  - Differential taste responses of mouse chorda tympani and glossopharyngeal nerves
      to sugars and amino acids.
AB  - The differential taste responses of the chorda tympani (CT) and the
      glossopharyngeal (GL) nerves in preweanling and adult mice were examined by
      comparing magnitudes of responses to six sugars and 10 amino acids. The results
      indicate that for sugars the responses of the CT nerve are greater than those of
      the GL nerve while for umami and essential amino acids the responses of the GL
      nerve are greater than those of the CT nerve. Such differential taste responses
      of the CT and GL nerves does not prominently change during development.

PMID- 8309631
TI  - Effect of prolonged administration of clonidine on [3H]PN 200-110 and [125I]omega
      conotoxin binding in mouse brain.
AB  - The effect of chronic exposure to clonidine or morphine on clonidine- and
      morphine-induced analgesia in mice was examined. Binding of L- or N-type calcium
      channel antagonist to cortical membrane fractions was also compared between these
      groups of mice. A decrease in the analgesic effect of clonidine and morphine was
      observed following prolonged administration of clonidine or morphine. Binding of
      [3H]PN 200-110, an L-type calcium channel antagonist, decreased following
      prolonged administration of clonidine whereas it increased after morphine
      treatment. On the other hand, a significant increase of [125I]omega-conotoxin, an
      N-type calcium channel antagonist, binding was observed after chronic clonidine
      or morphine treatment. These results will be discussed in relation with the
      possible development of cross-tolerance between clonidine and morphine through
      the change in calcium channels, more specifically in N-type channels.

PMID- 8309633
TI  - Upregulation of the pro-opiomelanocortin gene in spinal motoneurones in muscular
      dystrophy in mice.
AB  - Pro-opiomelanocortin (POMC) mRNA was detected in motoneurones of mice using
      histochemical in situ hybridization and cDNA oligonucleotide probes for the
      adrenocorticotropin (ACTH) 4-11 and beta-endorphin 1-8 regions of POMC. Staining
      for POMC mRNA was negligible in motoneurones in normal adult mice but in
      dystrophic mice the mRNA was present in > 60% of the ventral horn cells. It is
      concluded that neuropathic change in motoneurones is accompanied by upregulation
      of the POMC gene and synthesis of POMC-derived peptides.

PMID- 8309634
TI  - Messenger RNAs from chick muscle encode a motoneuronal survival-promoting factor.
AB  - The survival of motoneurons requires a trophic factor derived from the target
      muscles, but the nature of this trophic factor is not known. We examined whether
      skeletal muscle expresses mRNAs encoding survival-promoting factors for
      motoneurons. Messenger RNAs were purified from hindlimbs of chick embryos and
      injected into Xenopus oocytes for translation. The media conditioned by
      incubation of the injected oocytes were applied to chick embryos during the
      natural cell death period of lumbar motoneurons. This procedure significantly
      reduced the magnitude of natural motoneuronal death. The conditioned media also
      promoted the survival of motoneurons cultured from chick embryos.

PMID- 8309635
TI  - Electrophysiological identification of horizontal synaptic connections in rat
      visual cortex in vitro.
AB  - The presence of intrinsic horizontal synaptic connections in rat visual cortex
      was explored electrophysiologically using in vitro slice preparations.
      Intracellular recordings were made from pyramidal neurons located in the
      superficial and deep layers. Electrical stimulation at the gray matter in the
      same or different layers but 0.8-2.7 mm apart from the recording site evoked
      compound synaptic potentials composed of excitatory and inhibitory postsynaptic
      potentials of fast and slow time courses. Glutamate blockers, DNQX (5 microM) and
      kynurenate (2 mM) reduced the excitatory postsynaptic potential (EPSP), and GABAB
      receptor antagonist, phaclofen (0.5 mM), abolished the inhibitory postsynaptic
      potential of the slow time course. EPSP of the fast time course followed 20 Hz
      repetitive stimulation in the medium of high Ca2+ (6.0 mM) and Mg2+ (4.0 mM)
      concentration, suggesting that this fast EPSP was monosynaptic. Conduction
      velocity of the fibers mediating the monosynaptic EPSP was estimated to be 0.15
      0.55 m/s. These results provide physiological evidence for the horizontal
      synaptic connections in the rat visual cortex, which had been previously
      suggested by morphology.

PMID- 8309636
TI  - Incurvation of early embryonic neural retina by acetylcholine through muscarinic
      receptors.
AB  - Acetylcholine could induce the incurvation of neural retina to form a cup
      structure by muscarinic receptors in vitro. Neural retinae isolated from chick
      embryos were cup-shaped, but, it soon became flat in a normal bath solution. Then
      addition of acetylcholine caused an incurvation of the retina remaking the
      initial cup-structure. Ca2+ was involved in this movement since a calcium
      ionophore A23187 could also induce the folding of neural retina. Acetylcholine
      caused a rise in cytoplasmic Ca2+ concentration even in a Ca(2+)-free bath
      solution as measured with Fura-2. Atropine completely blocked both of the Ca2+
      rise and the incurvation of neural retina by acetylcholine. It was suggested that
      the Ca2+ mobilization from intracellular reservoirs triggered the contractile
      movement to fold the embryonic neural retina.

PMID- 8309637
TI  - Oral administration of idebenone, a stimulator of NGF synthesis, recovers reduced
      NGF content in aged rat brain.
AB  - The relationship between nerve growth factor (NGF) and senile dementia of the
      Alzheimer type is of interest. We demonstrate here that the oral administration
      of idebenone, a stimulator of NGF synthesis in vitro, produced recovery of
      reduced NGF content in aged rat brain. Twenty-one-day successive administration
      of idebenone produced significant recovery of reduced NGF content in the frontal
      cortex and parietal cortex of aged rats. These results suggest that NGF content
      in the brain is low in aged rats and that oral administration of idebenone leads
      to a recovery of this reduction.

PMID- 8309638
TI  - Selective loss of calbindin D28K-immunoreactive neurons in the cortical layer II
      in brains of Alzheimer's disease: a morphometric study.
AB  - To investigate the relationship between neuronal death and intracellular calcium
      homeostasis in brains from patients with Alzheimer's disease (AD), we
      quantitatively analyzed morphological changes of calbindin-immunoreactive
      neurons. Neuronal counts were made in the autopsy brains from 6 control and 6 AD
      patients. Calbindin-immunoreactive neurons were mainly distributed in cortical
      layer II and were selectively lost in the AD brains. Further, the number of
      calbindin-immunoreactive neurons showed a negative correlation with age in the
      control group. These findings strongly suggest that age-related reduction of
      calbindin-immunoreactive neurons may be exaggerated in AD brains and change in
      calcium homeostasis may be involved in the pathogenesis of AD.

PMID- 8309640
TI  - Quantal behaviour of synaptic transmission can be statistically examined using
      the Fourier line spectrum of the histogram of synaptic potentials.
AB  - A statistical approach to reveal the quantal behaviour of postsynaptic potentials
      (PSPs) is described. This includes: (1) obtaining the Fourier line spectrum
      (decomposition into harmonics) of the PSP histogram; and (2) testing the null
      hypothesis, 'the spectrum is that of white noise', using an ANOVA. The harmonic
      that rejects the hypothesis will indicate the regular peaks in the histogram,
      i.e., the quantal size of PSPs. The method was tested using published results of
      three experimental studies in central synapses and yielded the quantal sizes
      close to those derived from other methods. However, using three examples of
      published simulation studies (where the quantal model of synaptic transmission
      was known a priori), it was shown that the approach can estimate quantal sizes of
      PSPs more reliably than other methods.

PMID- 8309639
TI  - Reactive changes of glial cells after optic nerve axotomy in adult rats.
AB  - We have studied the glial response to optic nerve axotomy in vitro. Glial cells
      were obtained from normal and crush-axotomized optic nerves. In cultures from
      axotomized nerves, large numbers of astrocytes, oligodendrocyte progenitors and
      mature oligodendrocytes were found. Significantly fewer astrocytes and
      oligodendrocyte progenitors were present in cultures from normal nerves, mature
      oligodendrocytes did not occur. Proliferation and maturation of oligodendrocyte
      progenitor cells was only observed in cultures from axotomized nerves, suggesting
      the regulatory influence of blood-derived factors which are not present in normal
      nerves after in vitro axotomy. These data show that optic nerve injury enhances
      the ability of astrocytes, oligodendrocytes and their precursors to survive
      and/or proliferate in vitro.

PMID- 8309641
TI  - Heroes in health care: yesterday and today.

PMID- 8309642
TI  - Medical history: a letter written two centuries ago.

PMID- 8309643
TI  - Action myoclonus after cerebral anoxia.
AB  - Intention or kinesogenic myoclonus is uniquely one of many different movement
      disorders that if recognized and treated, early or late, responds to treatment.
      Posthypoxic intention myoclonus appears to be a syndrome associated with a
      variety of interacting biochemical mechanisms.

PMID- 8309645
TI  - How to get paid by workers' compensation.

PMID- 8309644
TI  - Primitive thought process and mental illness.

PMID- 8309646
TI  - Creating an agenda for women's health.

PMID- 8309647
TI  - Saccharin's aversive taste in rats: evidence and implications.
AB  - In most biobehavioral research using rats as subjects, saccharin is viewed as a
      "sugar substitute"--sweet, palatable, and conveniently lacking in calories. This
      characterization has merit: Saccharin seems to share some sensory, affective, and
      motivating properties with sugars. This paper focuses on saccharin's lesser
      known, aversive properties. Evidence of saccharin's distinctive taste in rats is
      reviewed, followed by discussion of several modulating variables. Procedures that
      influence rats' responses to saccharin and their measurement are summarized, and
      the argument is advanced that saccharin can be used to study the relationship of
      taste and ingestion to learning, stress, and emotional processes in rats and
      humans.

PMID- 8309649
TI  - Do the organs of the labyrinth differentially influence the sympathetic and
      parasympathetic systems?
AB  - It has long been recognized that the vestibular system plays a major role in
      autonomic control. The nature of this control remains in dispute, however, as
      some evidence points to a vestibularly mediated parasympathetic activation,
      whereas other evidence points to a sympatho-excitatory role for labyrinthine
      outputs. A theoretical explanation is offered that attempts to resolve this issue
      by postulating that the utricles exert a predominantly sympatho-excitatory
      influence via their interactions with brain noradrenergic pathways, while the
      semicircular canals (and possibly saccules) increase parasympathetic tone via
      their cholinergic brain stem and cerebellar projections. This explanation is
      relevant for understanding the vestibular role in orthostatic regulation, motion
      sickness, oculomotor control, and in many disorders or situations associated with
      neurochemical or autonomic imbalances.

PMID- 8309648
TI  - Fluoxetine: a spectrum of clinical applications and postulates of underlying
      mechanisms.
AB  - The antidepressant efficacy of fluoxetine in major depression has been briefly
      reviewed. A brief outline of dose selection, therapeutic onset, and
      pharmacokinetics of fluoxetine were made. The potential use of the drug in
      management of various psychiatric conditions has been examined. These include
      obsessive-compulsive disorder and related variances, anorexia nervosa, bulimia
      nervosa, Tourette's syndrome, and trichotillomania. The suggested use of
      fluoxetine in pain relief in certain diabetics, premenstrual syndrome, and
      migraine headache were assessed. The reports on the use of fluoxetine in panic
      disorders, paraphilias, and related conditions and in the management of substance
      abuse, alcoholism, and cocaine abuse, were summarized and elaborated upon. A
      composite of preliminary reports cited in literature pertinent to the potential
      of fluoxetine in treatment of abusing injurious behavior, dysthymic disorder,
      fibrositis, postanoxicaction myoclonus, pathologic jealously, personality
      disorder, pseudobulbar affect, and social phobia were also reviewed. Fluoxetine
      pharmacological profile may be extended to cover a relative wide range of
      application, provided future controlled studies confirm the preliminary data
      found in the literature.

PMID- 8309650
TI  - Aggression in humans: what is its biological foundation?
AB  - Although human aggression is frequently inferred to parallel aggression based on
      testosterone in nonprimate mammals, there is little concrete support for this
      position. High- and low-aggression individuals do not consistently differ in
      serum testosterone. Aggression does not change at puberty when testosterone
      levels increase. Aggression does not increase in hypogonadal males (or females)
      when exogenous testosterone is administered to support sexual activity.
      Similarly, there are no reports that aggression increases in hirsute females even
      though testosterone levels may rise to 200% above normal. Conversely, castration
      or antiandrogen administration to human males is not associated with a consistent
      decrease in aggression. Finally, changes in human aggression associated with
      neuropathology are not consistent with current knowledge of the neural basis of
      testosterone-dependent aggression. In contrast, human aggression does have a
      substantial number of features in common with defensive aggression seen in
      nonprimate mammals. It is present at all age levels, is displayed by both males
      and females, is directed at both males and females, and is not dependent on
      seasonal changes in hormone levels or experiential events such as sexual
      activity. As would be expected from current knowledge of the neural system
      controlling defensive aggression, aggression in humans increases with tumors in
      the medial hypothalamus and septal region, and with seizure activity in the
      amygdala. It decreases with lesions in the amygdala. The inference that human
      aggression has its roots in the defensive aggression of nonprimate mammals is in
      general agreement with evidence on the consistency of human aggressiveness over
      age, with similarities in male and female aggressiveness in laboratory studies,
      and with observations that some neurological disturbances contribute to criminal
      violence. This evidence suggests that human aggression has its biological roots
      in the defensive aggression of nonprimate mammals and not in hormone-dependent
      aggression based on testosterone.

PMID- 8309652
TI  - Inferring regional brain activity from evoked potential fields on the scalp.
AB  - A new method is described to calculate epicortical potential fields from scalp
      fields based on linear algebra. It requires detailed anatomical information, for
      each subject, obtained from MR images. The calculation is validated in a physical
      model of the human head and applied to human subjects. The results suggest that
      the method yields reliable epicortical fields that help to localize evoked
      cortical activity in humans.

PMID- 8309651
TI  - Human menstrual synchrony: a critical assessment/.
AB  - This review on menstrual synchrony in human females has four purposes: (a) to
      determine whether or not the phenomenon exists, and whether it differs in the
      various groups studied: roommates in dormitories, roommates in private
      residences, close friends, work groups, mothers-daughters; (b) to assess the
      magnitude of its effect, i.e., to what extent does the single factor of living
      together affect menstrual synchrony?; (c) to examine the effects of menstrual
      related factors, social interaction factors, and personality on menstrual
      synchrony; (d) to assess whether the findings support a pheromonal or common
      environmental explanation of menstrual synchrony. Several methodological issues
      are also discussed.

PMID- 8309653
TI  - Strategies for 3-D visualization of ocular structures.
AB  - The ability to visualize noninvasively the internal structure of the body has
      been widely utilized in clinical and research applications. Current tomographic
      structural imaging modalities, i.e., x-ray computed tomography (CT) and magnetic
      resonance imaging, produce image data which can be processed to reveal the three
      dimensional surface of an internal object using surface rendering, or
      alternatively, the surface and internal details of the object using volume
      rendering. To take full advantage of these techniques, the acquisition and
      preparation of the tomographic data must be optimized for the imaging modality,
      for the target tissue, and for the specific visualization needs of the structure
      of interest. Strategies for optimizing each of these parameters are presented
      using, as an example, an x-ray CT study of a bony orbital fracture.

PMID- 8309654
TI  - Laser-tissue interaction and artifacts in confocal scanning laser ophthalmoscopy
      and tomography.
AB  - The goal of the present study was to analyze the interaction between incident
      laser light and retinal tissue in confocal scanning laser ophthalmoscopy and
      tomography. We examined the change in axial intensity distribution during
      evaluation of the retinal surface topography in macular and optic nerve head
      evaluation in normal volunteers and patients with different retinal diseases.
      Additionally, we examined a model eye with a model cyst and human globes in an
      eye mounting chamber. We found that confocal scanning laser tomographs record
      specular reflected light originating from intraocular surfaces as well as light
      scattering from deeper retinal structures. Concave and convex retinal surfaces
      and eye movements may influence accurate topographic detection. Knowledge of the
      exact mechanism of image formation in confocal tomography is of great importance
      for the understanding of validity of these measurements. Proper identification of
      observed artifacts and preventive measures will increase the utility,
      reproducibility, and validity of this technology.

PMID- 8309655
TI  - Positron emission tomographic studies of cortical function in human amblyopia.
AB  - Positron emission tomography has confirmed that amblyopia is a visual disorder
      manifested by functional abnormalities in cerebral cortex. Studies of local
      cerebral blood flow and glucose metabolism as indicators of brain function in
      amblyopia are reviewed. Also presented is evidence for functional similarity of
      normal calcarine cortical responses during deprivation of high spatial
      frequencies by optical blur, to the responses during visual stimulation of
      amblyopic eyes. Recent evidence is presented concerning the quantitative
      relationship between behavioral measures of visual function in amblyopic eyes,
      and functional measures such as visual evoked potentials and blood flow increases
      in calcarine cortex.

PMID- 8309656
TI  - Enhancement of retinal images: pros and problems.
AB  - Evaluation of retinal images is essential to modern ophthalmic care. With the
      advent of image processing equipment, digital recording and processing of retinal
      images is starting to replace the standard film based fundus photography. The
      ability to enhance images is cited as one of the major benefits of this expensive
      technology. This paper critically reviews the practices employed in the image
      enhancement literature. It is argued that the papers published to date have not
      presented convincing evidence regarding the diagnostic value of retinal image
      enhancement. The more elaborate studies in radiology suggest, at best, modest
      diagnostic improvement with enhancement. The special difficulties associated with
      the demonstration of an improved diagnosis in ophthalmic imaging are discussed in
      terms of the diagnostic task and the selection of study populations.

PMID- 8309657
TI  - The application of confocal microscopy to the study of living systems.
AB  - A unique tandem confocal microscope (TSCM) has been developed that permits
      noninvasive imaging in vivo of the eye and many other organ systems in real time
      in situ. The application to the study of microphysiological processes in vivo is
      described and illustrated for the cornea, kidney, liver, epididymis, muscle, and
      adipose tissue. Novel applications are shown for studying the healing of wounds
      in four dimensions (x, y, z, t) in single animals over time at the cellular
      level. Application to clinical diagnostic use in humans is also demonstrated.
      When combined with Laser Scanning Confocal fluorescence microscopy, the TSCM
      offers a unique new imaging paradigm for experimental biology and medicine with
      great potential for use in neuroscience and many other disciplines.

PMID- 8309658
TI  - Medical-legal aspects of placental examination.

PMID- 8309659
TI  - Nineteenth century obstetrical practice: a different view.

PMID- 8309660
TI  - Pregnancy in patients with idiopathic thrombocytopenic purpura: assessing the
      risks for the infant at delivery.
AB  - The objective of this review is to estimate the risk of severe thrombocytopenia
      at birth and minor or major morbidity for the infant of a pregnancy complicated
      by immune thrombocytopenic purpura. English language publications on immune
      thrombocytopenic purpura in pregnancy from January 1980 to December 1990 were
      used. Manuscripts considered for infant risk assessment fulfilled the following
      criteria: 10 or more entrants, reported fetal platelet samples (cordocentesis,
      scalp sampling or cord sample at birth), and provided all infant platelet data.
      All other data not fulfilling these criteria are reported. The main results were
      11 manuscripts reporting 288 live-born infants fulfilled the criteria enabling
      assessment of infant risk. There were no deaths or intracranial hemorrhages in
      these studies and secondary morbidity occurred in 3.5 per cent (95 per cent CI
      1.4-5.6 per cent). An infant platelet count of less than 50 x 10(9) per liter was
      reported in 10.1 per cent (95 per cent CI 6.6-13.6 per cent) and an infant
      platelet count of less than 20 x 10(9) per liter occurred in 4.2 per cent (95 per
      cent CI 1.9-6.5 per cent). Neither cordocentesis, scalp sample, nor umbilical
      cord sampling at birth altered the outcome of these infants and minor morbidity
      occurred equally in vaginal and cesarean births. Smaller case reports (less than
      10 entrants) significantly over-estimated the prevalence of severe infant
      thrombocytopenia and secondary morbidity. All deaths and intracranial hemorrhages
      were reported in manuscripts which did not specify the timing of infant platelet
      count determination; thus the relationship of these events to the event of
      birthing was unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309661
TI  - Adenomyosis: a deja vu?
AB  - Adenomyosis is a relatively frequent finding in series of hysterectomies
      performed for menorrhagia and dysmenorrhea. Evident selection biases of the
      available studies on adenomyosis have always limited the possibilities of
      defining the real clinical importance of the condition. Until now the only
      certain diagnoses have been made by histopathologists on uteri removed at
      surgery, but recently various sufficiently accurate techniques have been
      suggested which allow diagnosis on the uterus in situ. With the these methods it
      might be possible to obtain correct information on the epidemiologic
      characteristics of adenomyosis and to clarify whether it has a pathogenic role in
      unexplained ovulatory menorrhagia and juvenile dysmenorrhea. Furthermore,
      resectoscopic treatment has been proposed in some mild forms of adenomyosis to
      avoid hysterectomy, whereas it seems improbable that medical treatment can offer
      a definitive solution. The adoption of standard histologic criteria for
      adenomyosis seems important. Until this is done, it will be difficult to
      establish whether adenomyosis is really a disease or merely a paraphysiologic
      condition.

PMID- 8309662
TI  - Amniotic fluid assessment.
AB  - Amniotic fluid assessment is a tool for the evaluation of fetal well-being.
      Because of the uterine cavity being irregular direct evaluation is difficult and
      subsequently, indirect techniques have been utilized. The three ultrasound
      techniques currently used for the evaluation of amniotic fluid include 1) maximum
      vertical pocket, 2) subjective assessment, and 3) amniotic fluid index. A review
      of these techniques show that the amniotic fluid index technique is valid, and
      the subjective technique and the amniotic fluid index technique appear to have a
      good inter- and intraobserver variability. All three techniques have been shown
      to predict peripartum morbidity and mortality when they define decreased amniotic
      fluid. Amniotic fluid volume is a weak predictor of morbidity and should be used
      in conjunction with other fetal biophysical variables to predict perinatal
      outcome.

PMID- 8309663
TI  - Rhesus immunization in pregnancy: a review.

PMID- 8309664
TI  - Basic questions on intrauterine insemination: an update.

PMID- 8309665
TI  - Amnioinfusion: a review.
AB  - Amnioinfusion is a commonly practiced technique used for intrapartum improvement
      of the fetal condition. Room temperature normal saline (0.9 per cent) infused
      through an intrauterine pressure catheter has been used to alleviate variable
      decelerations, dilute thick meconium, and improve the intrauterine environment.
      Randomized studies comparing amnioinfusion to no therapy have shown that
      amnioinfusion is associated with lower cesarean delivery rates, decreased numbers
      of operative deliveries, and improved umbilical artery and venous blood gas
      values. Amnioinfusion also has been suggested as means to instill antibiotics
      into an infected uterine cavity, or the uterine cavity of a woman with preterm
      premature rupture of the membranes. Transabdominal amnioinfusion may be used to
      improved prenatal ultrasound evaluation in pregnancies associated with
      oligohydramnios. Complications of amnioinfusion include umbilical cord prolapse,
      uterine overdistention, fetal bradycardia, and one report of possible amniotic
      fluid embolism. Overall, amnioinfusion seems to be a safe and effective technique
      to improve the intrauterine milieu.

PMID- 8309666
TI  - Scientists continue quest for the link between electromagnetic fields, cancer.

PMID- 8309667
TI  - Be prepared.

PMID- 8309668
TI  - When sick building complaints arise...

PMID- 8309669
TI  - Weight of evidence links obesity, fitness to carpal tunnel syndrome. Companies
      implementing wellness programs experience a reduction in CTS incidence.

PMID- 8309670
TI  - A violent state of mind?

PMID- 8309672
TI  - The vessel architecture of the pars plana in the cynomolgus monkey, rat and
      rabbit eye. A scanning electron microscopic study of plastic corrosion casts.
AB  - In the cynomolgus monkey, rabbit and rat the architecture of the pars plana
      vasculature was investigated using scanning electron micrographs of resin casts.
      The most complex vessel architecture was found in the cynomolgus monkey. Here,
      the pars plana venules have affluxes from the ciliary processes, ciliary muscle
      and iris. Numerous interconnections between these venules exist in the central
      portion of the pars plana. Arterial affluxes reach the pars plana not until the
      choriocapillaries. The variations of this architecture in the rat and rabbit are
      not only caused by the different size of the ciliary muscle and its
      vascularization. In the rat the most peripheral part of the uveal supply of the
      retina represents a transition form between pars plana venules and the
      choriocapillaries. In the rabbit, two vascular layers exist in the pars plana
      while in the cynomolgus monkey and rat the pars plana vessels spread out in one
      plane. The functional significance of the vessel architecture and the species
      differences are discussed.

PMID- 8309671
TI  - Reports detail problem of violence in the workplace.

PMID- 8309673
TI  - Glycation of human lens crystallins: effect of age and aspirin treatment.
AB  - Human lenses of three different ages were used to study the effect of age and
      aspirin treatment on glycation of alpha-, beta- and gamma-crystallins. Soluble
      lens proteins were subjected to in vitro glycation with 5 mM [14C]glucose in the
      presence and absence of 10 mM aspirin. With crystallins from a 27-year-old lens
      alpha-crystallin was the most readily glycated protein. Glycation of all
      crystallins decreased substantially (37-77%) in 46- and 67-year-old lenses
      indicating an age-dependent decline in glycation sites. On the basis of a
      sensitive chemical assay for protein-bound glycogroups in lenses of 2-82 years of
      age this decline is apparently due to a 60% increase in in vivo glycation.
      Aspirin did not show any selectivity with regard to its ability to inhibit
      glycation of various crystallins. Irrespective of the age glycation of all
      crystallins was inhibited to a varying extent.

PMID- 8309674
TI  - Prostacyclins in diabetes: an electrophysiological study.
AB  - Twelve patients with juvenile (insulin-dependent, type I) diabetes were treated
      either with prostacyclins or placebo in a double-masked randomized study. The
      electroretinogram (ERG) was recorded before, 1 day and 8 months after treatment.
      An analysis of variance and covariance was carried out to evaluate possible
      treatment or time effects on the a and b waves and the oscillatory potentials of
      the ERG. Mean values of potentials displayed a decrease of amplitude and an
      increase of latency over the follow-up period in all patients. No statistically
      significant difference between treated and placebo groups could be proven.

PMID- 8309675
TI  - Cis-hydroxyproline inhibits adhesion, migration and proliferation of cultured
      rabbit keratocytes.
AB  - Recruitment of keratocytes into injured corneal stroma, and secretion of proteins
      including collagen in the cells are essential for wound healing of the corneal
      stroma. We examined the effect of a proline analog, cis-hydroxyproline, on the
      adhesion, migration and growth of rabbit keratocytes in vitro. This agent
      decreased the plating efficiency, migration and growth of the keratocytes in a
      dose-dependent manner. Reduction in these cellular activities may reflect altered
      functions of pericellular proteins such as collagen. Further studies are needed
      to determine which specific protein is involved.

PMID- 8309676
TI  - Effects of ischemia-reperfusion on light-evoked alkalinization outside rod
      photoreceptors in the cat retina.
AB  - The effects of ischemia-reperfusion on the light-evoked alkalinization, which
      reflects the metabolism of rod photoreceptors, were studied in the dark-adapted
      cat retina in vivo. We recorded the pH value in the extracellular space
      surrounding rod photoreceptors with double-barreled H(+)-selective
      microelectrodes. The light-evoked alkalinizations at the outer nuclear layer were
      diminished during reperfusion after 10-30 min of ischemia which was induced by an
      increase of the intraocular pressure above the arterial systolic pressure. This
      result suggests that the rod metabolism might be suppressed during reperfusion
      after ischemia.

PMID- 8309677
TI  - Effects of some opiates and opioid peptide eyedrops on ocular melatonin
      regulation in rabbits.
AB  - Levels of melatonin in rabbit eye tissues were detected by radioimmunoassay.
      Solutions of met-enkephalin, leu-enkephalin, alpha-endorphin and beta-endorphin
      were given topically. Met-Enkephalin and alpha-endorphin lowered levels of
      melatonin in the iris, iris root-ciliary body, retina and choroid; leu-enkephalin
      raised levels in the retina and lowered them in other tissues. beta-Endorphin
      only lowered levels in the iris root-ciliary body. DAGO (a mu agonist) given i.v.
      lowered levels of melatonin in the iris, iris root-ciliary body and retina. The
      delta and sigma agonists given i.v. only lowered levels in the iris root-ciliary
      body, and a kappa agonist given i.v. raised levels in the ciliary body. No opiate
      binding sites could be detected in the rabbit iris or iris root-ciliary body for
      any class of receptor. Our data suggest opioids may be useful for treating
      glaucoma.

PMID- 8309678
TI  - Retinal pigment epithelium adhesion to Bruch's membrane is weakened by
      hemicholinium-3 and sodium iodate.
AB  - We have studied the effects of hemicholinium-3 (HC-3), an outer segment and
      retinal pigment epithelium (RPE) toxin and sodium iodate, an RPE toxin, on
      retinal and RPE adhesion in rabbits. During the first 3 days after intravitreal
      HC-3, the force required to peel retina from RPE fell to 50% of normal, and large
      patches of RPE separated from Bruch's membrane and adhered to the peeled retina.
      The same phenomena were observed during the first 100 min after intravenous
      sodium iodate. Beyond 3 days after HC-3, and 100 min after sodium iodate, the
      peeling force became even weaker, but separation occurred at the subretinal space
      or by fragmentation of RPE cells. Acute RPE toxicity probably accounts for the
      initial weakening of the bond between RPE and Bruch's membrane.

PMID- 8309680
TI  - [Current possibilities of malaria chemoprophylaxis].
AB  - The number of chloroquine-resistant Pl. falciparum malaria cases in the last
      decade dramatically increased. This fact causes significant problems not only in
      the therapy but in the malaria chemoprophylaxis as well. Presently, in accordance
      with the WHO's recommendations, the drug of choice in the malaria
      chemoprophylaxis is mefloquine. Other drugs can be used only when there is a
      problem (medical or other) in mefloquine-use. Halofantrine (Halfan) or the so
      called "double-acting" drugs (e.g. Fansidar) are not recommended in the malaria
      chemoprophylaxis.

PMID- 8309679
TI  - Aldose reductase inhibition and the phosphorus-31 profile of the intact diabetic
      rat lens.
AB  - Diabetic metabolic change and response to aldose reductase inhibition in the
      Wistar rat lens were examined with phosphorus-31 (31P) nuclear magnetic resonance
      (NMR) spectroscopy. To avoid artifacts in sample preparation, we used freshly
      excised lenses and acquired NMR data for 20 min immediately after lens
      extraction. The results showed a diabetes-induced time-dependent loss of ATP and
      phosphorylcholine (PC), an increase in alpha-glycerophosphate (alpha-GP) and
      inorganic phosphate and the appearance of sorbitol-3-phosphate (S-3-P) and
      fructose-3-phosphate (F-3-P). Oral but not topical dosing of an aldose reductase
      inhibitor, 5-(3-ethoxy-4-pentyloxyphenyl)-2,4- thiazolidinedione, resulted in a
      positive dose-response correlation characterized by a restoration of PC, S-3-P
      and F-3-P to the prediabetic level; however, alpha-GP and ATP were only partially
      normalized. The significance of the 31P change was further discussed.

PMID- 8309681
TI  - [Primary malignant melanoma of the lung and lower respiratory tract].
AB  - After detailed analysis of the international special literature, the authors
      found--together with their own two patients--only 18 cases, considered primer
      malignant melanoma of the lower respiratory tract and/or lung. Of the accepted
      criteria, they dispute the obduction's absolute evidentiary role, because among
      primer patients there are the most who survives, even a decade. In seven cases
      tumour was located endobronchially and in one patient in the trachea. It was
      manifested endobronchially and on the dependent lung-areas, simultaneously in two
      patients and merely parenchymally, in eight. There was a successful resection in
      fourteen of 18 cases. Survival was influenced primarily by the operability
      depending on distension of the tumour. Besides procedures forming opinions,
      bronchoscopy and histological examinations of bioptatum gained this way play a
      greater role than usual in determining the tumour's primarity, localisation,
      operability and type of surgery, respectively. Namely, only operated patients can
      rely on a long survival.

PMID- 8309682
TI  - [Major theoretical and practical aspects of publications].
AB  - The author discusses some ideas concerning the sharing of scientific
      informations. The fundamental goal of the latter is to serve the readers as
      perfectly as possible. A physician of research ambitions may valuable contribute
      to the progress of applied sciences but this must not jeopardize the medical care
      of the patients. Reading relevant literature is one of the prime obligations of
      all doctors. The author raises some dilemmas and question concerning how to write
      publications while he attempts to clarify matters. He emphasizes that the
      importance of correctness of a publication is second to none. The problem of
      fragmentation and that of "double publication" is also briefly discussed. The
      author elaborates on how to identify the co-authors and the sequence they appear
      in the publication. He provides some hands- on advice as to the concise language
      and abbreviations. He enters the list for the qualitative improvement rather than
      quantitative increase of publications in Hungary.

PMID- 8309683
TI  - [Pharmacology of colchicine and its use in dermatology].
AB  - This study provides a summary about an old drug, colchicine, which has been used
      in medicine for two thousand years. It emphasizes the importance of this agent in
      the treatment of dermatologic diseases, especially in vasculitis. One of the aims
      of the study to spread the application of colchicine in the therapeutic
      management.

PMID- 8309684
TI  - [Acute parotitis in children previously vaccinated against mumps].
AB  - Children who had previously received Morbilli-(Mumps) Rubella (MMR) vaccine
      developed parotid swelling which was diagnosed as acute parotitis 7 days to 2
      years following inoculation. Blood samples from each of the patients were tested
      for the following virological parameters: Mumps-virus, Parainfluenza-viruses
      (PIV) type 1., 2., 3., Respiratory Syncytial Virus (RSV), Epstein Barr Virus
      Capsid Antigen (EBVCA) IgM, IgA, IgG immunofluorescent test (IFT) and EBVCA IgM,
      IgG ELISA (HUMAN); Epstein Barr Virus Early Antigen (EBV EA) IgG IFT; Adenovirus,
      Influenza A, B Complement Fixation (CF) test. Some of the sera were examined for
      CMV IgM, IgG ELISA (Organon Teknika) and Human Parvovirus B19 IgM, IgG
      recombinant ELISA (Bender) too. Nine cases were interpreted as a clinical
      reaction of mumps vaccination. Beside the clinical reaction of mumps vaccination.
      Beside the clinical reaction of mumps vaccination, the etiological role of PIV-1,
      PIV-2, PIV-3 and PIV-1,2 was confirmed in four, three, one and one patients,
      respectively. The alonely etiological agent was the PIV-2 in four and PIV-2 and
      Epstein-Barr virus together were in one patients, respectively. The etiology was
      unknown in one patient. The results show the importance both of the broad
      spectrum precise serologic studies and of the skillful interpretation in the
      exact diagnosis of the acute parotitis to identify parotitis either as a
      consequence of the mumps vaccine or vaccine failure. The correct diagnosis of
      acute parotitis can influence the booster mumps vaccination practice too.

PMID- 8309685
TI  - [Changes in osteocalcin serum levels in children with growth hormone deficiency
      during substitution therapy].
AB  - Osteocalcin (OC), a specific marker of osteoblast activity, was measured in 21
      short, growth hormone deficient (GHD) children before and during 2 years of
      growth hormone (GH) therapy. Anthropometric and serum measurements were performed
      in every three-month during the first year (15 patients) and after the second
      year (16 patients). Mean OC concentration was significantly lower in GHD children
      compared to normal value (11.9 +/- 2.1 ng/ml (n = 15) and 11.4 +/- 2.5 ng/ml (n =
      16) vs. 17.5 +/- 4.9 ng/ml). During the GH treatment serum OC increased
      continuously: 15.5 +/- 2.4 - 20.5 +/- 8.2 - 26.1 +/- 8.6 - 25.1 +/- 9.8 ng/ml (n
      = 15) and 24.9 +/- 9.1 ng/ml (n = 16) then decreased (16.6 +/- 9.7 ng/ml). OC
      level measured in the 9th and 12th months was markedly higher than in normal
      children (p = 0.01 and p < 0.001). IN CONCLUSION: 1. Serum OC is low in short
      statured GHD children. 2. In the first 9-12 months of GH therapy OC raises
      continuously exceeding the normal mean value. 3. During the second year of GH
      treatment OC decreases to the normal level. 4. OC concentration measured does not
      correlate with change of other parameters observed (growth velocity, bone
      maturation, height for age). 5. Although OC is a sensitive marker of bone
      formation, it has no prognostic value concerning the growth.

PMID- 8309686
TI  - [Importance of the examination level in the ultrasonic diagnosis of knee joint
      meniscus injuries].
AB  - One hundred and five cases have been selected at random out of the first 500
      ultrasonographic examinations of the knee joint. The ultrasonographic findings
      have been compared to the arthroscopic operative descriptions. Examinations have
      been performed on intact knee joint menisci of dead young persons to improve
      specificity, sensitivity and accuracy of the method. Based on these experiences,
      optimal method of examination of the semilunar cartilage is reported. Special
      attention is given to the advantages of two-view (cross and longitudinal section)
      examinations. Against the opinion of many authors it is stated that longitudinal
      section image of the meniscus provides more information even in cases of
      longitudinal ruptures, while radial injuries can be recognized only in this
      plane.

PMID- 8309687
TI  - [A case of successful operation of left atrial myxoma causing cerebral embolism].
AB  - The authors describe the case report of a young woman in whom a left atrial
      myxoma causing cerebral embolism was diagnosed by echocardiography. On the ninth
      day after the development of neurologic symptoms the tumor was excised by an
      emergency intervention. After the operation the condition of the patient improved
      considerably. In connection with the case the authors underline the role of
      echocardiography in the detection of sources of embolism.

PMID- 8309689
TI  - ["Medicalization" and ethics].

PMID- 8309688
TI  - [The career of Elek Hints (1893-1966].

PMID- 8309690
TI  - [Injuries of the knee ligaments].

PMID- 8309691
TI  - [Knee joint function and the cruciate ligaments. Biomechanical principles for
      reconstruction and rehabilitation].
AB  - Trauma to the knee joint with disruption of one or both cruciate ligaments will
      start a biological response: inflammatory reactions, neurophysiological changes
      due to disruption of afferent nerve endings, and biomechanical changes which will
      ultimately lead to instability (functional and mechanical) as well as to early
      degenerative changes. Treatment, whether operative or non-operative, has to be
      based on a sound knowledge of biological and biomechanical principles. Cruciate
      ligament graft positioning, fixation, pre-tensioning, operative technique for
      reconstruction, and rehabilitation will all have influence on each other. All
      these factors therefore have to be balanced to achieve good mid- to long-term
      results.

PMID- 8309692
TI  - [Diagnosis of acute and chronic injuries of the knee joint].
AB  - Following a general review of the basic principles of knee examination, the
      specific instability tests of the different ligaments are explained. The
      pathophysiology, the pathomechanic and the diagnostic evidence of these
      instability tests are shown. The diagnosis of meniscal and cartilaginous lesions
      are not discussed.

PMID- 8309693
TI  - [Current state of evaluation of knee ligament lesions. The new IKDC knee
      evaluation form ].
AB  - Various scoring systems have been proposed for quantification of the disability
      caused by knee ligament injuries and to evaluation of the results of their
      treatment. None of them was found worldwide acceptance, mainly because all
      scoring systems attribute numerical values to factors that are not quantifiable,
      after which the arbitrary scores for parameters that are not comparable with each
      other are added together. For these reasons a group of knee surgeons from Europe
      and America met in 1987 and founded the International Knee Documentation
      Committee. A common terminology and an evaluation form were created. This form is
      the standard form for use in all publications on results of treatment of knee
      ligament injuries. It is a concise one-page form and includes a documentation
      section, a qualification section and a evaluation section. For evaluation there
      are four problem areas (subjective assessment, symptoms, range of motion and
      ligament examination). These are supplemented by four additional areas that are
      documented but are not included in the evaluation (compartmental findings, donor
      site pathology, X-ray findings and functional tests). The form can be used pre-
      and postoperatively and at follow-up. The Committee also laid down that in a
      publication the minimum follow-up time for short-term results should be 2 years,
      for medium-term results, 5 years, and for long-term results, 10 years. Most of
      the sheet is devoted to the qualification section. It is called "qualification"
      and not "scoring" section because no scores are given. Each parameter is
      qualified as "normal", "nearly normal", "abnormal" or "severely abnormal". This
      qualification is less subjective and emotional than "very good", "good", "fair"
      and "poor". No knee and no knee function can be better than normal, and it is
      rather doubtful whether any knee that has been operated on can ever be "normal"
      again. For evaluation, the parameters of the four problem areas "subjective
      assessment", "symptoms", "range of motion" and "ligament examination" are
      qualified for the group qualification. The worst qualification within the group
      is taken as the group qualification. The worst group qualification is taken as
      the final evaluation. If the knee is abnormal in any of the problem areas it
      cannot be entered as normal knee. For knees with chronic pathology it is also
      possible to evaluate the sum of levels of improvement or deterioration of all
      groups compared with the preoperative evaluation. The committee also recommends
      that terms describing knee ligament problems should be used according to the
      definitions published by Noyes et al.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8309694
TI  - [Treatment of collateral ligament ruptures of the knee joint].
AB  - Functional treatment of the medial collateral ligaments (grades I and II) gives
      the best results. Both, experimental results and clinical experience thus far,
      show that such treatment leads to a short period of morbidity and always gives a
      good functional result. Any minimal residual instability can be successfully
      compensated for. Functional treatment is only possible if the cruciate ligaments
      are intact. Severe ruptures (grade III) can also be treated with functional
      therapy, but with certain qualifications (not in the presence of axial deviation,
      cruciate instability or previous meniscectomy). Isolated lesions of the lateral
      collateral ligaments are very rare; severe combined ruptures of the capsule and
      ligaments are treated surgically.

PMID- 8309695
TI  - [The healing process after cruciate ligament repair in the sheep model].
AB  - The patellar tendon autograft is widely used in cruciate ligament replacement.
      Knowledge of the basic processes involved in graft healing and of factors
      regulating the healing process is still limited. The patellar tendon and cruciate
      ligament are morphologically and biochemically distinct, which reflects the
      different mechanical forces acting on them. Based on morphological studies in
      posterior cruciate ligament replacement in a sheep model, the patellar tendon
      autograft undergoes a remarkable transformation process during healing. Distinct
      healing phases similar to those in would healing can be differentiated. During
      the phase of necrosis and degeneration the graft tissue becomes disorganized and
      mechanically weak. During the following phase of revitalization, which is
      characterized by revascularization, cellular proliferation and formation of
      collagen and other components of the extracellular matrix, the mechanical
      properties gradually improve. Even after the phase of remodeling the autograft
      tissue differs structurally and mechanically from a ligament, suggesting that the
      autograft only heals to a scar-like replacement tissue. The lack of a fascicular
      structure, the widespread presence of type III collagen and fibronectin, and the
      predominance of thin collagen fibrils correlate with a maximum stress of 60% and
      an elastic modulus of 70% compared with control values. In the sheep model
      cartilage alterations in the treated knees are similar to those in controls even
      though reconstruction of the posterior cruciate ligament cannot restore joint
      stability of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309697
TI  - [Cruciate ligament prostheses. Techniques, results and perspectives].
AB  - Artificial ligaments have been used as augmentation devices, scaffolds, ingrowth
      ligaments and even prostheses. The augmentation devices rely entirely on the
      autologous tissue for their function, whereas each of the other types functions
      more or less as a prosthesis. These devices can function only for a limited time
      and they are very sensitive to the implantation technique. Problems involve
      debris formation, synovitis and finally ligament rupture. There is also a loss of
      stability in the treated knee over the first 2-3 postoperative years. The
      clinical results obtained in various studies with the prosthetic devices are not
      satisfactory. The problem of reconstruction of a knee with ligamentous
      instability is far greater than that involved in replacing the ligament only.

PMID- 8309696
TI  - [Indications for anterior cruciate ligament reconstruction--current surgical
      techniques, choice of transplant].
AB  - At present there is still a great deal of uncertainty about the natural history
      of ruptures of the ACL. The literature reveals that a significant number of
      secondary meniscus lesions and chondral damage results, when a high activity
      level is maintained. Reconstruction of the ACL now improves objective stability
      and decreases the meniscectomy rate in a large number of cases. Replacement with
      a patellar tendon or semitendinosus graft and augmented repair give better
      results than primary suture of the ligament. A limited arthrotomy or an
      arthroscopic technique should be used for reconstruction of the ACL. Two tunnel
      techniques with a lateral incision and single incision techniques with a femoral
      half tunnel are used. There is no consensus at present on the optimal graft
      source and surgical technique for ACL reconstruction.

PMID- 8309698
TI  - [Reconstruction of the cruciate ligaments with allogeneic transplants.
      Techniques, results and perspectives].
AB  - The authors have used allografts for reconstruction of the cruciate ligaments in
      over 600 cases since 1985. Advantages are the reduced operative trauma and the
      unlimited availability of high-quality grafts even in multiple ligament
      reconstructions. Arthroscopic techniques are available for reconstruction of the
      anterior and the posterior cruciate ligament, which makes arthrotomies and large
      skin incisions unnecessary. The grafts of choice are the bone-patellar tendon
      bone preparation and the Achilles tendon with bone bloc. No specific
      complications were observed with the use of allograft material in this series.
      Results show a high subjective acceptance of the procedure among the patients,
      with a high rate of return to pre-injury sports activities following ACL
      reconstruction. Objective stability was restored in over 70% of these cases. All
      cases with posterior instability had 3+ posterior drawer preoperatively. At
      follow-up, almost normal stability had been restored in 50%. Further research
      must focus on the biological processes that take place during incorporation of
      these tissues and on better techniques of graft processing and sterilisation. At
      present, the risk of disease transmission must be considered and discussed with
      the patient.

PMID- 8309699
TI  - [Therapy of arthrofibrosis after ligament reconstruction of the knee joint].
AB  - The development of arthrofibrosis in a serious complication of knee ligament
      injury or knee ligament surgery. The fibrosis is caused by a pathologic quantity
      or quality of collagen fiber formation in the knee or in the capsular structures,
      causing irreversible loss of range of motion, restricted patellar motion and
      finally patella baja with frank osteoarthritis of the patella. The major factors
      inducing fibrosis are notch impingement, development of a cyclops on an anterior
      cruciate ligament graft, scarring of the fat pad and the retinacula and adhesions
      in the recesses of the joint. Our therapeutic concept includes aggressive
      physiotherapy and an early arthroscopic procedure if conservative measures fail.
      A posterior capsulotomy is performed from a posteromedial arthrotomy in cases
      with flexion contracture persisting over a number of years. In 16 patients
      reviewed 17 months after arthroscopic treatment of arthrofibrosis the average
      improvement in range of motion was 13 degrees for extension and 25 degrees for
      flexion. A further 7 patients with chronic flexion contractures persisting for 1
      year or more were treated with a posterior capsulotomy and reviewed 18 months
      after surgery. The average gain for extension was 15 degrees in these patients at
      follow-up.

PMID- 8309700
TI  - [Revision surgery after failed anterior cruciate ligament repair].
AB  - Not every reconstruction of the anterior cruciate ligament is successful.
      Possible reasons for failure are renewed severe trauma, inadequate fixation of
      the transplant, an isometric mistake, weak transplant material, an anterior
      cruciate ligament reconstruction performed in isolation in a complex unstable
      knee, or prosthetic ligaments. Revision surgery is indicated when patients
      complain about the recurrence of knee instability. Preoperative diagnostic
      procedures must include X-rays with the knee in defined positions in order to
      determine drill hole courses and visualize any signs of arthrosis and the
      patellar position. Revision surgery is hampered by disadvantageously placed drill
      holes, exhaustion of the supply of transplant material, secondary instabilities,
      gonarthrosis or a possible arthrofibrosis. During rehabilitation a variable knee
      position is imperative, because of the different procedures that might need to be
      implemented.

PMID- 8309701
TI  - [Therapy of posterior and posterolateral knee instability].
AB  - The natural course after posterior cruciate ligament (PCL) tear is a slow process
      of degeneration starting in the medial compartment. Functional disability is
      mainly present in those instabilities that are combined with posterolateral
      insufficiency. The surgical treatment at present mainly addresses these combined
      types of posterior-posterolateral instability. It is generally agreed that suture
      of the torn PCL alone is insufficient and augmentation with autologous
      structures, such as the patellar ligament, are mandatory. Synthetic augmentation
      to facilitate after treatment is another adjunct. Because of the difficulty of
      precise tibial tunnel placement a two-stage procedure is advocated, an anterior
      approach with the patient supine being used for femoral graft placement. If a
      posterior approach with the patient prone is used, a straight posterior incision
      is made between the two heads of the gastrocnemius and the neuromuscular bundle.
      With this approach the tibial bone block is placed in a trough. The accuracy of
      graft placement and the immediate functional aftertreatment facilitated by the
      use of osseous fixation of a synthetic augmentation device at both ends have made
      better results of surgical reconstruction of the PCL possible.

PMID- 8309702
TI  - [Replacement of the posterior cruciate ligament and Clancy biceps tenodesis.
      Technique and results].
AB  - Operative treatment of chronic combined posterior/posterolateral knee instability
      is difficult. If the osseous anatomy of the leg causes a varus loading of the
      knee, we perform a high tibial valgus osteotomy as first step. Since 1988 we have
      been using a special drill guide system for reconstruction of the posterior
      cruciate ligament. The tunnels are drilled with the instruments placed through
      the notch and with image intensifier control. We prefer a bone-tendon-bone
      patellar tendon autograft or allograft for replacement of the posterior cruciate
      ligament. The procedure is combined with a biceps tenodesis as described by
      Clancy. Rerouting of the biceps tendon over the origin of the lateral collateral
      ligament puts tension on the posterolateral corner and augments the collateral
      ligament. It was possible to review 16 out of 18 cases treated in this way at an
      average of 18 months after surgery. Preoperatively, all had a 2 to 3+ posterior
      drawer and a reversed pivot shift. At follow-up, 10 had a 1+ posterior drawer, 3
      a 1-2+ drawer and 3 a 2+ drawer; 5 patients still had a reversed shift. KT-1000
      measurements revealed 8 mm (4-12 mm) posterior translation. The Lysholm Score
      averaged 83 points and the Tegner Score 4.0 at follow-up.

PMID- 8309703
TI  - [Biological, biomechanical and clinical concepts of after-care following knee
      ligament surgery].
AB  - Rehabilitation of the anterior cruciate ligament (ACL) continues to be a topic of
      intense interest among surgeons and therapists. Numerous experimental studies
      have demonstrated that motion and a certain amount of stress are necessary for
      ligament healing. In experimental and clinical studies closed kinetic chain
      exercises have been proven to be safe already in the early phase of
      rehabilitation. Since 1987, over 2900 patients who have undergone ACL
      reconstruction using the central one-third of the bone patellar tendon bone graft
      have followed our accelerated rehabilitation protocol. Follow-up of the patients
      reveals early return to athletic activity and maintenance of long-term stability.
      Our 1987 accelerated rehabilitation program continues to be modified, with less
      constraints placed on the postoperative patient in our present rehabilitation
      protocol. Past patient non-compliance to previously established protocols still
      yielded excellent results that demanded further investigation. Gradually we
      developed a four-phase rehabilitation protocol. The initial phase encompasses the
      preoperative period with the goal of resolving swelling and regaining full
      motion. The second phase involves the initial two weeks post ACL reconstruction
      and focuses primarily on wound healing, full extension, control of swelling, and
      leg control. The third phase (two to five weeks) involves increasing flexion,
      developing a functional gait, and resuming activities of daily living. The fourth
      phase (> five weeks) identifies a safe return to competitive athletics. With this
      accelerated rehabilitation protocol a decreased postoperative morbidity was noted
      without jeopardizing the long term stability of the ACL reconstructed knee.

PMID- 8309704
TI  - A philological note on some words concerning itch and related cutaneous
      sensations.

PMID- 8309705
TI  - Flexion reflexes following anterolateral cordotomy in man: dissociation between
      pain sensation and nociceptive reflex RIII.
AB  - Nociceptive flexion reflexes (RIII response) of the lower limbs were recorded
      after unilateral cervico-thoracic anterolateral cordotomy (ALC) in 7 patients.
      Pre-operative recordings were also obtained in 1 patient and follow-up
      observations in 3 patients. Flexion reflexes ipsilateral to cordotomy remained
      normal after surgery. Conversely, responses contralateral to the cordotomy
      exhibited two consistent postoperative changes: first, the RIII reflex was always
      dissociated from subjective pain, i.e., it appeared in the absence of any pain
      sensation, and, second, the RIII was depressed in the limb contralateral to ALC
      in 5 of 7 patients. RIII attenuation ranged from slight reduction to total
      abolition, and proved to be reversible in 2 of 3 patients tested during the
      follow-up. The reappearance of withdrawal reflexes was never accompanied by a
      recovery of pain sensation in the stimulated limb. We conclude that the
      dissociation between flexion reflexes and pain sensation, which was evidenced
      even in case of depressed RIII responses, should be attributable to the surgical
      lesion of spinothalamic fibers. Dissociation between RIII and subjective pain is
      a landmark indicating a lesion of the spinothalamic fibers, and may be used for
      the clinical assessment of spinothalamic dysfunction. Conversely, RIII depression
      after ALC does not depend upon the surgical lesion to the spinothalamic axons,
      but may be secondary to interruption of ascending spinoreticular fibers in the
      anterolateral quadrant, and/or of descending excitatory axons in the ventral
      cord.

PMID- 8309706
TI  - Reflex sympathetic dystrophy of the hand: an excessive inflammatory response?
AB  - In 23 patients with reflex sympathetic dystrophy (RSD) of the hand, scintigraphy
      with indium-111 labeled human non-specific polyclonal immunoglobulin G (In-111
      IgG) was performed to investigate whether inflammatory characteristics are
      present in RSD. Both blood flow and accumulation over 48 h were assessed.
      Nineteen patients had increased flow to the affected hand, and 3 had decreased
      flow. One patient had bilateral RSD. Exercise provoked aggravation of complaints
      and signs in all patients. The affected/non-affected hand ratio (target-to
      background, T/B) immediately before and after exercise did not change
      significantly. The T/B ratios 48 h after In-111-IgG injection were significantly
      higher in patients with RSD less than 5 months than in patients with RSD existing
      5 months or longer. The T/B ratios 24 and 48 h after In-111-IgG injection were
      not correlated with the flow T/B ratios. In fact, 2 of the 3 patients with a
      decreased flow showed excess accumulation on the late images. Significantly more
      patients with early RSD, existing less than 5 months, had a positive In-111-IgG
      scintigraphy (14 of 17) than the patients with late RSD (1 of 6). Increased
      vascular permeability for macromolecules, an important characteristic of
      inflammation, appears to play a role in the development of RSD. This phenomenon
      is not flow-dependent.

PMID- 8309707
TI  - Pain sensation during cold stimulation of the teeth: differential reflection of A
      delta and C fibre activity?
AB  - Cold stimuli of varying intensities were randomly applied to upper middle
      incisors of 12 healthy young subjects for a mean duration of 2 min by
      individually adapted thermodes the temperatures of which ranged from +30 degrees
      C to -30 degrees C. The subjects were asked to rate the magnitude of their pain
      sensations during application of the stimuli by means of a linear potentiometer
      according to a category scale. After each stimulus, they were asked to describe
      the quality of their pain sensations. Cold stimulation of the teeth evoked pain
      sensations were reproducible that in subsequent trials and could be graded
      according to stimulation intensity. Below certain individually different
      threshold thermode temperatures the onset of a stimulus was followed, after a
      short latency (1.6 +/- 1 sec), by a sharp and shooting pain sensation which
      immediately decreased after reaching its maximum value while the stimulus was
      still present. The mean maxima of the pain intensities were correlated to the
      thermode temperature. In general, this first pain component was followed by a
      second one (latency: 29.9 +/- 6.3 sec) with a lower threshold temperature, less
      of an increase in rate and lower magnitude. This was described as a dull, burning
      pain which was difficult to localize. The human pain ratings are compared to
      recordings of intradental nerve fibres in the cat and, under the assumption that
      the response behaviour of human pulpal nerve fibres is comparable to that of the
      cat, we hypothesize that the first pain component is evoked by intradental A
      delta fibres exhibiting their typical phasic response behaviour and firing during
      the initial steep temperature decrease. After some seconds, intradental
      temperature reached values sufficient to evoke C-fibre activity associated with
      the second pain component.

PMID- 8309708
TI  - Role of norepinephrine in the interaction between the lateral reticular nucleus
      and the nucleus raphe magnus: an electrophysiological and behavioral study.
AB  - We have previously demonstrated that the nucleus raphe magnus (NRM) sends a
      predominantly inhibitory projection to the lateral reticular nucleus (LRN);
      however, the pharmacology of this pathway is not known. The purpose of this study
      was to examine the role of norepinephrine in the NRM-LRN system using both
      electrophysiological and behavioral techniques. Sixty-nine LRN cells were
      recorded extracellularly. Cells were tested for their response to noxious and
      innocuous peripheral stimulation applied to the dorsal body surface. The majority
      of cells were classified as wide dynamic range, with inhibition being the
      predominant response; receptive fields were located primarily on the tail and
      hind limbs. The effect of excitatory amino acid glutamate (GLU) administration
      into NRM (GLU-NRM) was tested on all 69 cells. GLU-NRM inhibited 55 of 69 LRN
      cells tested; 7 cells were excited and 7 cells did not respond. Thirty-nine LRN
      cells were tested for their response to norepinephrine (NE) iontophoretically
      applied in LRN (NE-LRN). Two distinct types of effects were noted. In 9 cells,
      both NE-LRN and GLU-NRM produced a strong inhibition, with the magnitude of
      effect between the 2 drugs significantly correlated. In a second group of cells
      (n = 12), GLU-NRM produced an inhibitory effect while NE-LRN had no effect on the
      cells' baseline firing rate. However, when the 2 drugs were applied
      simultaneously, NE-LRN blocked the inhibitory effects of NRM stimulation. The
      effect of the alpha 2-receptor antagonist yohimbine (YOH) on NRM-evoked responses
      was tested in 30 LRN cells. The majority of these cells were inhibited by GLU
      NRM. Similar to the dichotomous effect noted by NE-LRN, YOH applied
      iontophoretically in LRN (YOH-LRN) had two predominant effects on NRM-produced
      inhibition. In 14 of 27 cells, YOH-LRN significantly potentiated the inhibitory
      effects of NRM stimulation by increasing the duration of the inhibitory epoch an
      average of 100 sec. In 7 of 27 cells, YOH directly applied in LRN partially
      antagonized NRM-evoked inhibition. In a second series of experiments,
      microinjection cannulas were placed within NRM and LRN in order to determine the
      effect of blocking alpha 2-receptor activity within LRN on NRM stimulation
      produced analgesia in an intact animal. Administration of D,L-homocysteic acid in
      NRM resulted in a significant increase in baseline tail-flick latency of
      approximately 140%. Pretreatment with YOH (3 micrograms in 0.5 microliter) in LRN
      resulted in a significant potentiation of this analgesic effect.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8309709
TI  - Increasing the reliability and validity of pain intensity measurement in chronic
      pain patients.
AB  - This study examined the effects of increasing the number of assessments on the
      reliability and validity of measures of average pain intensity. Two hundred
      chronic pain patients completed 2 weeks of hourly pain ratings. A series of
      regression analyses were performed, and test-retest stability, internal
      consistency and validity coefficients were computed to address 4 questions. (1)
      Are chronic pain patients' reports of pain similar from one day to another? (2)
      What is the reliability and validity of a single rating of pain intensity when
      used as an indicant of average pain? (3) How many assessments (data points) are
      required to obtain estimates of average pain intensity with adequate to excellent
      psychometric properties? (4) How important is it to sample pain from different
      days? The results were consistent with predictions based on patients' self
      reports of their pain and on psychometric theory. First, the majority of patients
      did not report similar levels of pain from one day to another, and average pain
      scores calculated from ratings obtained from a single day were less stable than
      those calculated from ratings obtained from multiple days. Also, and as expected,
      the results indicate that a single rating of pain intensity is not adequately
      reliable or valid as a measure of average pain. However, a composite pain
      intensity score calculated from an average of 12 ratings across 4 days
      demonstrated adequate reliability and excellent validity as a measure of the
      average pain in this sample of chronic pain patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8309710
TI  - Genetic factors influence the development of mechanical hypersensitivity, motor
      deficits and morphological damage after transient spinal cord ischemia in the
      rat.
AB  - Genetic influence on the sensory, motor and histopathological outcome of
      transient spinal cord ischemia was studied in Sprague-Dawley (SD), spontaneously
      hypertensive (SH) and Wistar-Kyoto (WKY) rats. Ischemia caused minor motor
      deficits and no identifiable morphological damage in the spinal cord of the
      majority of SD rats after 1 min laser irradiation. However, severe mechanical
      hypersensitivity, characterized by an allodynia-like reaction to non-noxious
      tactile and pressure stimuli, was observed for several days in SD rats after
      spinal cord ischemia. SH rats exhibited less allodynia than SD rats, but
      developed profound motor deficits. WKY rats, the normotensive progenitor of SH
      rats, developed both severe mechanical allodynia and motor impairment after
      spinal cord ischemia. Histological examination revealed that there was
      significantly more extensive morphological damage in the epicenter of the
      irradiated segments of the spinal cord in SH and WKY rats than in SD rats after
      transient spinal cord ischemia. The results indicated that SH rats are more
      resistant to the development of central pain after central nervous system
      ischemia, but SH and WKY rats are more susceptible to neuronal damage than SD
      rats. Thus, genetic variability can lead to variable predisposition for the
      development of pain and spinal cord damage after ischemia. Such factors may
      underlie the wide variability in the occurrence of pain after central nervous
      system injury in humans.

PMID- 8309711
TI  - Excitatory effects on neck and jaw muscle activity of inflammatory irritant
      applied to cervical paraspinal tissues.
AB  - A study was carried out in 19 anaesthetized rats to determine if the
      electromyographic (EMG) activity of jaw and neck muscles could be influenced by
      injection of the inflammatory irritant mustard oil into deep paraspinal tissues
      surrounding the C1-3 vertebrae. The EMG activity was recorded ipsilaterally in
      the digastric, masseter and trapezius muscles and bilaterally in deep neck
      muscles (rectus capitis posterior). In comparison with control (vehicle)
      injections, mustard oil (20 microliters, 20%) injected into the deep paraspinal
      tissues induced significant increases in EMG activity in the neck muscles in all
      the animals and in the jaw muscles in the majority of the animals; the effects of
      mustard oil were more prominent in the former. The EMG response evoked by mustard
      oil injection was frequently reflected in two phases of enhanced activity. The
      early phase of the increase in EMG activity was usually initiated immediately
      following mustard oil injection (mean latency: 20.4 +/- 17.7 sec) and lasted 1.6
      +/- 1.1 min. The second phase occurred 11.3 +/- 7.6 min later and lasted 11.0 +/-
      8.1 min. Evans Blue extravasation was apparent in the deep paraspinal tissues
      surrounding the C1-3 vertebrae after mustard oil injection, and histological
      examination showed that mustard oil injection induced an inflammatory reaction in
      the rectus capitis posterior muscle. These results document that injection of the
      inflammatory irritant mustard oil into deep paraspinal tissues results in a
      sustained and reversible activation of both jaw and neck muscles. Such effects
      may be related to the reported clinical occurrence of increased muscle activity
      associated with trauma to deep tissues.

PMID- 8309712
TI  - First onset of common pain symptoms: a prospective study of depression as a risk
      factor.
AB  - This report examined first onset rates of 5 common pain symptoms and assessed, on
      a prospective basis, whether depressive symptoms at baseline were associated with
      onset risks. Adult Health Maintenance Organization (HMO) enrollees (n = 1016)
      were interviewed in 1986 about their history of each of 5 pain conditions (back
      pain, severe headache, chest pain, abdominal pain and temporomandibular disorder
      (TMD) pain). Three years later, this sample was re-interviewed (n = 803) to
      measure site-specific first onset rates. The Symptom Checklist 90-Revised (SCL-90
      R) Depression scale was administered at baseline and at 3 year follow-up. Over
      the three year follow-up interval, rates of first onset were: 17.7% for back
      pain; 4.2% for severe headache; 3.0% for chest pain; 3.1% for abdominal pain; and
      6.5% for TMD pain. Onset rates of persistent pain and of chronic pain dysfunction
      were substantially lower, but over 1% experienced onset of chronic pain
      dysfunction for back pain and for headache. There were not significant
      differences in onset rates of back pain, abdominal pain or TMD pain by severity
      or chronicity of depressive symptoms. Relative to the non-depressed, persons with
      moderate-to-severe depressive symptoms were more likely to develop headache and
      chest pain (adjusted odds ratios of 1.7 to 5.0). For headache and chest pain,
      onset risks were highest among the chronically depressed.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8309713
TI  - What does the BDI measure in chronic pain?
AB  - The Beck Depression Inventory (BDI) has been widely used to document the
      prevalence of depressive symptomatology in samples of chronic pain patients and
      as an outcome measure in studies of the psychological management of chronic pain.
      Several BDI items have a somatic content (sleep disturbance, fatigue, etc). Since
      chronic pain may have similar somatic effects, the significance of the total BDI
      score in this population is unclear. Two hundred and forty mixed chronic pain
      patients completed the BDI at screening interview for a psychologically based
      pain management programme; of these, 207 (mean age 50.1 years; 63% female) were
      later admitted to the programme when the BDI was readministered along with
      measures of pain, anxiety, pain-related cognitions, and physical performance. The
      mean BDI score of the sample was 18.1, with 71.7% meeting criteria (scoring 13 or
      more) for at least mild depression. A principal-components analysis of the BDI
      yielded 3 meaningful factors labelled: sadness about health, self-reproach, and
      somatic disturbance. Among the most frequently endorsed items were those loading
      on the somatic factor. The pattern of relationships between individual factor
      scores and measures of pain, mood, cognition, and physical functioning indicated
      that the use of the total BDI score may give a misleading impression of the
      nature and degree of affective disturbance in this group of patients. The
      implications of these findings for our understanding of BDI scores obtained by
      chronic pain patients are discussed.

PMID- 8309714
TI  - 'Mirror pain' in the formalin test: behavioral and 2-deoxyglucose studies.
AB  - Subcutaneous injection of a dilute formaldehyde solution (5 or 10%) into a hind
      paw induced, in the majority of rats, the appearance of 'mirror pain': licking
      the contralateral untreated hind paw 10-60 min after injection. Contralateral
      licking activity was much less frequent than the ipsilaterally directed one, but
      the overall intensities of the two responses were positively correlated.
      Qualitatively, the two behaviours were similar. Functional activity levels of the
      lumbar spinal cord, as revealed by the 2-deoxyglucose (2-DG) technique, were
      increased bilaterally over the first hour after unilateral hind limb formalin
      injection in unanesthetized, freely moving rats. The enhancement of the [14C]2-DG
      uptake could be detected both in dorsal and ventral horns, as well as in the gray
      matter surrounding the central canal, and the anterolateral and dorsolateral
      funiculi. These metabolic changes may reflect an enhancement of the functional
      activity of both interneuronal pools and units projecting to supraspinal centers,
      giving rise to a referred contralateral pain.

PMID- 8309715
TI  - Ipsilateral referral of pain following cordotomy.
AB  - We report a patient who developed ipsilateral referred pain following unilateral
      percutaneous cervical cordotomy (PCC). A right-sided PCC was performed on a 44
      year-old woman who had been suffering from left groin and thigh pain caused by a
      fibrosarcoma. PCC produced analgesia below T7 on the left side, and the pain
      disappeared. A novel spontaneous pain with prominent allodynia occurred
      postoperatively in the right infraclavicular region (C3-C4). Strong pressure on
      the left groin where severe spontaneous pain and tenderness had been before PCC
      increased the new pain, and an epidural block which produced analgesia below T10
      relieved the new pain. These facts indicate that the new pain was induced by
      afferent inputs from the originally painful region.

PMID- 8309716
TI  - [Immunomodulating effects of antibiotics influencing digestive flora].
AB  - Mucosal surfaces are habitats of the physiological microflora and are closely
      related to the mucosal immune compartment (mucosa-associated lymphoid tissue,
      MALT). Recently, considerable evidence has been accumulated showing that various
      members of the physiological microflora liberate low molecular weight peptides
      which, apparently, are essential for adequate immune responses of the host.
      Antibiotic decontamination (e.g. of the BALB/c-mouse intestinal tract) results in
      a lack of generation of immunopriming microbial peptides leading to
      immunosuppression. Biochemical analysis of the peptides revealed reproducible
      chromatographic fractions which selectively influence maturation, proliferation,
      and activation of lymphatic cells.

PMID- 8309717
TI  - [Are antibiotics immunomodulators?].
AB  - This review of the literature, although non complete, involving different
      observations, experiments and documented demonstrations, suggest the real
      importance of the interrelations existing between, the pathogenic bacteria, the
      specific and non specific reactions of the normal or infected host and the
      antibiotics. The bacterial infections are potent immunomodulators by causing
      significant alterations in one or more mediators of homeostasis (coagulation,
      complement, inflammation), inducing cellular and tissular alterations more or
      less dramatic depending upon the number, the virulence of the bacteria and the
      immune status of the host. Antibiotics in reducing the number of the infecting
      pathologic bacteria, in modifying their pathologic and virulence factors might
      them be considered as immunorestoring molecules. On the other hand, when large
      numbers of bacteria are killed rapidly by bactericidal antibiotics, their
      cytoplasmic enzymes or bacterial cell wall structures, are rapidly released
      locally and are able to amplify the various systems involved in the deleterious
      inflammatory reaction. Thus depending on their dose and their mode of action,
      antibiotics could be considered as immunomodulators, albeit indirectly in
      modifying the pathophysiology of the host, in inhibiting or enhancing the release
      of immunoreactive bacterial molecules. Moreover antibiotics have been shown to
      interfere directly on the non specific and specific defenses mechanisms. Until
      the recent years, only the immunotoxicological aspect has been evaluated,
      involving mostly the immunopharmacologic screening of the antibiotics effects on
      phagocytic cells or on the effectors of the immune responses. Several recent
      examples are given that illustrate a new approach looking at the molecular level
      of the cellular action of antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309718
TI  - [Isotypic regulation of antibodies and antibiotics].
AB  - Several reports have shown that antibiotics can in vitro interfere with many
      aspects of the immune response such as phagocytic processes, macrophage
      functions, T and B cell proliferation. Very few data on the effect of antibiotics
      on the antibody response were available. It is well known that the humoral immune
      response is sustained by different immunoglobulin isotypes (IgA, IgE, IgG or IgM)
      according to the antigen, its penetration route, the mucosal-associated lymphoid
      tissue, the genetic background and the age of the host. Such an isotypic
      regulation was very recently demonstrated to be closely related to some cytokines
      like interferon-gamma, interleukins (IL)-2, -4 and -10. We tested the effect of
      some cephalosporins on in vitro cytokine-dependent immunoglobulin production.
      Neither cefadroxil nor cefalexine had any modulating effect on pokeweed mitogen
      induced IgG and IgM production by normal human B-cells. In contrast, cefadroxil,
      and not cefalexine, blocked up to 90% of the in vitro IL-4-dependent IgE
      production by normal B lymphocytes. In the same way, this cephalosporin was able
      to inhibit the membrane expression of CD23 molecules (low affinity Fc-epsilon
      receptors) which is involved in phagocytic processes and in IgE regulation. The
      first target cell of the effect of cefadroxil was clearly shown to be monocyte
      macrophage lineage which were stimulated to produce prostaglandin E2 which down
      regulated CD23 membrane expression and IgE secretion. Such data showed that
      antibiotics were able to interfere with cytokine cascade which controlled the
      immunoglobulin isotype.

PMID- 8309719
TI  - [Antiviral chemotherapy: mechanisms of action, evaluation of activity, resistance
      and future developments].
AB  - Antiviral chemotherapy is based on the selective inhibition of intracellular
      virus multiplication. Inhibitors of viral DNA polymerases perfectly exemplifies
      this mode of action. In spite of their selectivity, some of these drugs are
      cytotoxic and all remain unefficient against latent viruses. Evaluation of
      antiviral activity requires in vitro sensitivity tests, in vivo studies on
      animals and virological analyses during clinical trials. This evaluation needs
      well standardized assays. The emergence of in vitro resistance reflects the
      occurrence of mutations regarding target enzymes. Clinical significance of
      antiviral drug resistance needs to be assessed in many circumstances, even if its
      association with immunodeficiency often leads to a clear therapeutic failure.
      Further developments will include the synthesis of novel inhibitors, study of
      drug associations and improvement of virological diagnosis techniques relevant to
      therapy.

PMID- 8309720
TI  - [Role of cytokines in the regulation of HIV expression].
AB  - The cytokine network, which is involved in the regulation of normal immune
      responses, may play a role in the pathogenesis of human immunodeficiency virus
      (HIV) infection, by altering the replication of HIV in target cells. In vitro
      data, suggest that certain cytokines like "tumor necrosis factor" alpha (TNF
      alpha) "granulocyte-macrophage colony-stimulating factor" (GM-CSF) and
      interleukin-6 (IL-6) could up-regulate HIV expression in T-cells and macrophages.
      Other cytokines like alpha interferon, are potent inhibitors of HIV replication.
      Surprisingly, the macrophage and the T-lymphocyte, the main source of cytokines
      in the body, do not produce any of these cytokines following HIV infection. B
      lymphocytes however, spontaneously release TNF alpha and IL-6, that might enhance
      HIV replication in nearby monocytes and T-lymphocytes. This situation may occur
      in lymph nodes, a major reservoir of HIV.

PMID- 8309721
TI  - [What is known about the cellular and molecular pharmacodynamics of
      nucleosides?].
AB  - 3'-azido-3'-deoxythymidine (zidovudine-AZT) was the first clinically approved
      reverse transcriptase inhibitor for the treatment of acquired immunodeficiency
      syndrome (AIDS) and recently, 2',3'-dideoxyinosine (didanosine-ddI) has also been
      approved in France. These nucleoside analogs have no intrinsic anti-HIV activity
      and must be metabolized to their respective 5'-triphosphates by means of kinases,
      nucleotidases, or other activating enzymes present naturally in cells. The
      presence and activity of the necessary intracellular enzymes for activation of
      nucleoside analogs is highly dependent on species, cell type, and cell cycle
      stage, illustrating the importance of cellular functions in the mechanism(s) of
      action or toxicity of nucleoside analogs. Although the apparent plasma
      elimination half-life of the parent drug varies between 1 and 2 hours, the active
      triphosphate derivatives have intracellular half-lives between 4 and 12 h with
      2',3'-dideoxyadenosine-5'-triphosphate (ddATP), the active component of ddl being
      one of the most stable with an intracellular half-life of 8 to 12 hours which
      result in relatively infrequent dosing as compared to other classes of potential
      anti-HIV drugs under development. The multifactorial mechanism(s) of toxicity of
      this class of drugs likely explains the different spectrums of toxicity observed
      with the various nucleoside analogs, and demonstrates the uniqueness of each
      compound. Recently, AZT-resistant strains have been isolated from AZT-treated
      patients, probably reflecting a sequential acquisition of amino-acid mutations in
      the HIV-RT. Of importance, cross-resistance was demonstrated with other compounds
      with an 3'-azido group, but no cross-resistance was detected with either ddl of
      2',3'-dideoxycytidine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309722
TI  - [Is resistance of human immunodeficiency viruses (HIV) to nucleoside analogs an
      indication for their combined use?].
AB  - HIV resistance to nucleoside analogues such as zidovudine (AZT) is to date a
      source of concern, even if its clinical significance is yet to be determined.
      Phenotypic and genotypic data concerning HIV resistance will be presented, then
      the potential benefits of nucleoside combinations will be discussed.

PMID- 8309723
TI  - [Are immunomodulators capable to improve the activity of nucleoside
      antiretroviral agents?].
AB  - Synthetic polyribonucleotides stimulate cells to produce interferons and other
      cytokines and increase both humoral and cell-mediated immunity. The
      polynucleotide complexes affect host defense system and may have antiviral
      properties. Studies in animal models of experimental viral infection may
      therefore be performed to define a possible strategy for their use in human
      disease. Antiviral properties of polyribonucleotides have been demonstrated in
      animals, especially in murine models of retroviral infection. In the early
      treatment of Friend virus infection, the antiretroviral effect of zidovudine is
      enhanced by combination with poly I poly C or poly A poly U. Polyribonucleotides
      also enhance the inhibitory effect of zidovudine on HIV replication in lymphocyte
      T or macrophage cultures. Therefore this class of compounds could be used in
      combination with antiviral agents in the treatment of HIV infection, especially
      when they induce no significant toxicity as it is the case for poly A poly U.

PMID- 8309724
TI  - [Visceral leishmaniasis resistant to conventional treatments: value of
      amphotericin B].
AB  - The reference treatment in visceral leishmaniasis is administration of antimonial
      compounds (Pentostam, Glucantime). Primary and secondary failures have been
      reported and may involve several mechanisms resulting in alterations in the T
      cell-dependent response, particularly in HIV-positive patients. Alternative
      agents proposed for use as single-drug therapy or in combination with other drugs
      include Lomidine, which carries a high risk of toxicity, allopurinol, cytokines
      (IL-2 and interferon gamma), and amphotericin B. Amphotericin B, in addition to
      effects on the metabolism of sterols in the wall of the protozoan, induces
      macrophage activation. This article illustrates the difficulty of treatment of
      visceral leishmaniasis by reporting the case of an immunocompetent 36-year-old
      patient whose bone marrow cultures remained positive after successive treatment,
      over 48 months, with two courses of Glucantime (60 mg/kg/day for 15 days), one
      course of allopurinol (10 mg/kg/4 weeks), two courses of Glucantime in
      combination with interferon gamma, splenectomy, and one course of Pentostam (20
      mg/kg/4 weeks). Bone marrow cultures became negative after administration of
      amphotericin B (1 mg/kg every 48 hours for 8 weeks). Cytokine studies disclosed
      defective production of IL-2, IL-1 beta, and IFN gamma. Amphotericin B seems to
      be a valuable alternative when conventional treatment fails. The liposomal form
      is especially promising.

PMID- 8309725
TI  - [Cytokines and severe infections].
AB  - In severe infections two factors play a part: the infectious agent and the
      response of the host. The response of the host involves production of a large
      number of endogenous mediators including a number of cytokines that are currently
      the focus of many studies: tumor necrosis factor (TNF alpha), interleukins (IL-1
      and IL-6), and interferon gamma (IGN gamma). These cytokines are part of the
      body's normal defense mechanisms but can have toxic effects when produced in
      excessive amounts. Although levels of these cytokines are often high in the blood
      of patients with sepsis, persistence of these elevations is the main indicator of
      severe infection. Experimentally, injections of TNF alpha and IL-1 reproduce the
      manifestations of severe sepsis. Mice that are genetically unable to produce TNF
      alpha are resistant to the injection of endotoxin. Severe sepsis can be prevented
      by pretreatment of animals with anticytokine agents (polyclonal and monoclonal
      antibodies and anti-receptor agents ...). Many issues remain unresolved: for
      instance, the experimental results obtained with an intravenous bolus of
      endotoxin or bacteria have not been confirmed in some animal models of subacute
      infection. These models may more closely resemble human infections. The
      interrelations between these cytokines are extremely complex. Synergistic effects
      do occur, but the effects of combinations of cytokines can be different from
      those of each cytokine given alone... It follows that therapeutic use in humans
      of anti-cytokine molecules is still an approach of uncertain outcome that will
      perhaps be clarified by ongoing multicenter clinical trials.

PMID- 8309726
TI  - [State of activation of polynuclear neutrophils and cytokines in acute
      respiratory distress syndrome in adults].
AB  - To gain further insight into the pathogenesis of the adult respiratory distress
      syndrome (ARDS), the authors studied possible relationships among the activation
      status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and
      the severity of lung injury in 31 patients: 15 with ARDS, 9 with severe pneumonia
      uncomplicated by ARDS, and 7 mechanically ventilated patients with neither ARDS
      nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry,
      the authors identified a subpopulation of PMN with an increased capacity to
      generate hydrogen peroxide after stimulation ex vivo in all three patient groups;
      significantly higher values were found in those with ARDS. The PMN stimulation
      index, a reflection of the degree of hyperresponsiveness, correlated with
      elevated levels of tumor necrosis factor alpha (TNF-alpha) in plasma, and both
      spontaneous and lipopolysaccharide (LPS)-induced TNF-alpha production by cultured
      monocytes. These biological expressions of PMN activation and cytokine generation
      both correlated with indices of the severity of lung injury, but not with the
      overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no
      relationship with either the degree of lung injury or PMN hyperresponsiveness. We
      conclude that TNF alpha-primed PMN may play a major role in the pathogenesis of
      ARDS-associated lung injury.

PMID- 8309728
TI  - [Proposed standardization of histo-oncologic diagnosis and terminology].

PMID- 8309727
TI  - [Effects of antibiotics on production of cytokines by human monocytes].
AB  - Antibiotics do not act alone but in conjunction with the host defence system. In
      particular, it has been shown that antibiotics can modify cytokine production.
      The authors reported here the effects of antibiotics which penetrate inside the
      cells, such as quinolones and macrolides, on the capacity of blood monocytes to
      produce IL-I alpha, IL-1 beta, TNF alpha and IL-6 in response to endotoxin.
      Antibiotics can exert a differential effect on cytokine production: in fact,
      quinolones, in vitro, at concentrations higher than 25 micrograms/ml decreased IL
      1 beta, TNF alpha and IL-6, while they do not modify IL-1 alpha. Moreover,
      ciprofloxacin orally administered (25 mg/kg for 7 days) transitory increased
      cytokine production. These results are discussed in terms of tissue
      concentration. Among the same family of antibiotics such as macrolides,
      differences on cytokine modulation were observed: spiramycin and erythromycin
      increased IL-6 production while roxithromycin did not exert any significant
      effect. All these results tend to prove that some antibiotics are
      immunomodulators; however interactions between antibiotics and immune responses
      are complex and studies with patients with infections will be necessary to a
      better understanding of these relationships.

PMID- 8309729
TI  - Multimedial data base and management system for self-education and testing the
      students' knowledge on pathomorphology.
AB  - The composition assumed our experience in creating and using multimedial data
      base of examination questions and management system, which is used for. This
      system is implemented on microcomputers compatible with IBM PC and works in
      network system Net Ware 3.11. The test questions exceeded 2000 until now. The
      packet consists of the two functionally individual programs: ASSISTANT, which is
      the administrator for the databases, and EXAMINATOR which is the executive
      program. This system enables to use text files and add images to each question,
      which are adjusted to display on standard graphics devices (VGA). Standard format
      of the notation files enables to elaborate the results in order to estimate the
      scale of answers and to find correlations between the results.

PMID- 8309730
TI  - Genetic and epigenetic mechanisms for the limited lifespan and ageing of normal,
      diploid cells.
AB  - The genetic basis of the limited lifespan and apparently programmed number of
      divisions in normal, diploid cells is discussed. Two different mechanisms may
      underlie a programmed inhibition of cell divisions before they age and die: 1. A
      genetic mechanism involving the CpG sequence in promotor regions of genes.
      Inactive, but gradually activated basic function genes such as ribosomal and
      energy metabolism genes, when inactive have their CpG promotor sequences
      methylated. During each cell division a proportion of 5-methyl cytosines will be
      oxidatively deaminated leading to C to T transitions. After a certain number of
      divisions all methylated CpG islands will be mutated with consequent loss of
      viability and cell death. 2. An epigenetic mechanism involving the methylated
      promotor sequences of silent growth control genes. After a certain number of
      divisions with incomplete maintenance methylation, the growth control genes will
      be derepressed with consequent cessation of proliferation, decline of metabolic
      activity, ageing, and death.

PMID- 8309731
TI  - Cytomorphometry of fine-needle aspiration biopsy material from the liver tumours.
AB  - The present study describes morphometric analysis of nodular changes examined by
      using fine-needle aspiration biopsy guided ultrasonographically. A group of 49
      patients with suspected neoplastic changes of the liver was studied including 4
      hepatocellular carcinomas, 21 neoplasms metastasizing to the liver, 23 non
      neoplastic changes. The whole material was divided into three major groups: A
      with neoplastic cells, B with non-neoplastic cells and C with suspected cells. In
      each case 100 cells were measured, and in each cell the surface area, maximal
      diameter and coefficient of shape of the cytoplasm, nucleus and nucleolus were
      measured. It was found that neoplastic cells have larger nuclei and nucleoli; the
      ratio of nucleus to cytoplasm was shifted in favour of the nucleus. The largest
      nucleoli are typical for hepatocellular carcinoma. Most rounded are cells of
      adenocarcinomas metastasizing to the liver. Morphometric measurements
      automatically isolate large liver cell dysplasia. The present study provides
      morphometric parameters of the hepatocytes in the cytological material, which may
      be the basis for further studies.

PMID- 8309732
TI  - Neuropathological study on the nucleus basalis of Meynert in mature and old age.
AB  - The nucleus basalis of Meynert (nbM) is the single major source of cholinergic
      innervation of the entire cerebral cortex. Data from human and animal studies
      suggest that brain cholinergic activity diminishes as a consequence of aging. The
      aim of this study was the description of the morphological changes in the nbM in
      normal aging. Our cases, who died of non neurological diseases and without
      dementia, were divided into three comparison groups on the basis of age at death;
      the young group (A)--10 brains of patients (mean age mean = 34.7), the mature
      group (B)--15 (mean = 55.2), the old group (C)--18 (mean = 75.0). Lipid affinity
      was characteristic of neurons of the nbM. It occurred in young cases and reached
      maximum in the mature age. Astrocytic gliosis (increase in GFAP-positive
      astrocytes) dominated in the group B and decreased in the group C. Fibrillary
      gliosis showed significant positive linear correlation with age (p < 0.001). The
      markable feature of the aging is significant cell loss in the nbM in association
      with advancing age (p < 0.05). The cellular loss in the nbM which projects to
      entire cortical mantle may be responsible for the cortical atrophy and disorders
      of higher cortical function that appear during normal aging.

PMID- 8309733
TI  - The level of immunoglobulins in the small and large intestinal mucosa from
      children with ulcerative colitis.
AB  - In 42 children 4 to 16 years old with ulcerative colitis by using peroxidase
      method and monoclonal antibodies we evaluated the presence of immunoglobulin A,
      M, G, E in the mucosa of the large and small intestines. It was found that the
      distribution of immunoglobulins in the acute phase was similar in the intestinal
      segments studied, which supports the opinion that the whole intestine has a
      common immune system playing a major role in the pathogenesis of the disease.

PMID- 8309734
TI  - Influence of thyroliberin (TRH) on hypothalamo-neurohypophysial vasopressin and
      oxytocin content of rats drinking 2% NaCl.
AB  - Rats drinking and libitum tap water or hypertonic (i.e., 2%) sodium chloride
      solution were given intracerebroventricularly (i.c.v.), during three days,
      thyrotropin-releasing hormone (TRH) in a daily dose of 200 ng dissolved in 10
      microliters of 0.9% sodium chloride. Treatment with TRH resulted in significantly
      increased hypothalamic oxytocin content in both euhydrated (i.e., given tap water
      ad libitum) and salt-loaded rats and vasopressin content only in euhydrated rats.
      Similarly, neurohypophysial vasopressin and oxytocin content significantly
      increased in animals drinking tap water or 2% sodium chloride during treatment
      with TRH. The present data suggest that TRH may be involved in some regulatory
      processes to vasopressin and oxytocin biosynthesis and release from the rat
      hypothalamo-neurohypophysial system.

PMID- 8309735
TI  - Amyloid tumour (amyloidoma) of the mediastinum.
AB  - A unique case of a surgically treated primary amyloid tumour of the mediastinum
      has been reported in a 40-year-old man. Immunohistochemical examinations revealed
      the presence of transthyretin and amyloid AA within the amyloid masses.

PMID- 8309736
TI  - Splenogonadal fusion. A case report.
AB  - A case of splenogonadal fusion in a 60/year-old man has been described. This
      congenital malformation in this very case was composed of an abnormal fusion
      between the spleen and epididymis. This is an 124th case reported in the
      literature.

PMID- 8309737
TI  - The effects of bedside pulmonary mechanics testing during infant mechanical
      ventilation: a retrospective analysis.
AB  - We examined the effects of regular bedside testing of pulmonary mechanics (PM) on
      the outcome of 468 acutely ill, mechanically ventilated neonates. During the
      first of two 18-month study periods, 217 infants were mechanically ventilated
      without the assistance of PM measurements. During the second 18-month period, 251
      infants were ventilated with the assistance of at least daily PM measurements.
      Using data obtained from the PM tests, we adjusted the infants' ventilators to
      maintain tidal volume, inspiratory time, and pressure-volume loops within
      predetermined limits. With the exception of the PM measurements, given the
      limitations of retrospective analyses, both groups of infants received identical
      medical and nursing care. The infants ventilated with the assistance of PM
      testing developed fewer pneumothoraces (4.0%; 10/251) vs. no PM testing, 10.1%
      (22/217); P < 0.05 by Chi-square analysis]. Infants weighing less than 1,500 g
      ventilated with the assistance of PM measurements had less intraventricular
      hemorrhage (IVH) overall, most notably, less grades I and II IVH (total IVH-PM
      testing, 39.1% vs. no PM testing, 65.7%; P < 0.01; Grades I-II IVH-PM testing,
      30.4% vs. no PM testing, 54.9%; P < 0.01). IVH incidence was decreased
      independent of pneumothorax occurrence. Survival rates, incidences of
      bronchopulmonary dysplasia, and durations of mechanical ventilation and
      hospitalization were similar. This retrospective analysis suggests that PM
      testing during infant mechanical ventilation reduces common acute ventilator
      associated complications.

PMID- 8309738
TI  - Continuous end-tidal CO2 in pediatric bronchoscopy.
AB  - In recent years flexible fiberoptic bronchoscopy (FFB) has been applied to
      children for diagnostic and therapeutic purposes. Sedation during FFB, along with
      introduction of the bronchoscope into the pediatric airway, may cause
      hypoventilation, leading to hypoxia and desaturation, even in the presence of
      oxygen supplementation. Arterial oxygen saturation is usually monitored by pulse
      oximetry (SpO2) during FFB. End-tidal PCO2 (P(etCO2)) monitoring is not routinely
      used. Twenty-two pediatric patients (15 days to 18 years old) undergoing FFB and
      receiving supplemental oxygen were studied prospectively and had continuous
      P(etCO2) and SpO2 measured before and during the procedure (bronchoscope at the
      carina or either main bronchus). Mean P(etCO2) (+/- SD) decreased from 33.9 (+/-
      6.0) mmHg before to 27.1 (+/- 12.1) mmHg during the procedure (P < 0.024).
      Concomitantly, mean SpO2 (+/- SD) also decreased from 99.9 (+/- 0.4)% before to
      95.7 (+/- 11.1)% during the procedure (P < 0.015). P(etCO2) changes seemed to
      precede the variations in SpO2, especially in young patients who experienced
      significant desaturation and decompensation during FFB. We conclude that PetCO2
      and SpO2 decrease during FFB in children, even with supplemental oxygen. We
      speculate that this reflects airway obstruction by the instrument. Further
      studies are needed to assess the utility of PetCO2 monitoring in pediatric FFB.

PMID- 8309739
TI  - The effect of age on oxygen desaturation during histamine inhalation challenge in
      normal infants.
AB  - Arterial oxygen saturation (SaO2) is usually measured during inhalation
      challenges in infants as desaturation has been demonstrated with provoked
      bronchoconstriction. We wished to examine whether measurement of SaO2 would
      provide a simple noninvasive indicator of respiratory function (RF) changes
      occurring during inhalation challenge in infants. Histamine inhalation challenges
      were performed longitudinally in 22 normal healthy infants at 4 and 26 weeks of
      age. RF was measured by calculating maximum forced expiratory flow at functional
      residual capacity (VmaxFRC) using the rapid thoracic compression technique.
      Airway responsiveness was assessed using histamine; the provoking concentration
      (PC) was that which caused a fall in VmaxFRC of at least 40% from baseline. The
      provocative concentration for an exact fall of 40% in VmaxFRC (PC40) from
      baseline was derived by linear interpolation. SaO2 was continuously monitored by
      pulse oximetry. One month old infants had higher SaO2 levels throughout the
      inhalation challenge in comparison to their SaO2 levels at 6 months of age.
      Significant falls in SaO2 were observed at the PC at both ages. However, at the
      age of 26 weeks the infants had greater median falls in SaO2 [PC, 4.5% (95%CI:
      3.0, 7.0)] compared to the response at age 4 weeks [3.0% (95%CI: 1.0, 4.0) (P <
      0.01)]. Median falls in VmaxFRC at the PC were not different between the ages.
      These results indicate an age-dependent discordance between airway and SaO2
      response in healthy infants during histamine-induced bronchoconstriction.

PMID- 8309740
TI  - Continuous positive airway pressure by nasal prongs in bronchiolitis.
AB  - Ten infants with evidence of impending respiratory failure from severe
      bronchiolitis were successfully treated with continuous positive airway pressure
      (NCPAP) with double nasal prongs. Their mean (SD) age was 6.7 (3.8) months and
      mean (SD) body weight was 7.1 (2.1) kg. Respiratory assessments were made
      immediately before and 2 hours after application of NCPAP. Clinical symptoms,
      signs, and arterial blood gases improved in all patients, with a significant fall
      in mean (SD) respiratory rate [71 (6) vs. 54 (9) per minute], mean (SD) heart
      rate (178(9) vs. 154(15) per minute], and mean (SD) partial pressure of arterial
      carbon dioxide [Paco2; 48.0 (13.9) vs. 42.4 (12.9) mmHg]. There was a significant
      rise in mean (SD) arterial blood pH [7.33 (0.05) vs. 7.37 (0.05)] and mean (SD)
      oxygenation ratio [Fio2/Pao2, 155 (25) vs. 175 (22)]. We believe NCPAP is an
      effective method, with numerous advantages in the treatment of severe
      bronchiolitis. Early application of NCPAP is suggested to avoid the need for
      mechanical ventilation.

PMID- 8309741
TI  - An isotopic study of nasal mucociliary transport in newborns: preliminary
      investigation.
AB  - The diagnosis of primary ciliary dyskinesia (PCD) depends on electron microscopic
      examination of cilia obtained from mucosal biopsies of the nasal turbinates or
      the trachea. This is an invasive, time-consuming, and expensive technique. The
      low incidence of this abnormality, the large number of infants and children with
      suggestive symptoms, and the lack of a reliable screening test make the decision
      to proceed with diagnostic biopsy a common problem in recurrent or chronic
      respiratory pediatric conditions. To improve this situation early in infancy,
      nasal mucociliary transport was evaluated in 10 normal newborns using the Tc-99m
      labeled seroalbumin technique, and the results obtained were compared with those
      corresponding to a newborn with Kartagener's syndrome. Transport velocity in
      normal newborns was similar to that observed in older children and in adults, in
      contrast to the tracer immobility seen in the affected newborn. This technique is
      simple, safe, objective, and well tolerated in this age group and might be used
      as an early screening test to ruling out PCD.

PMID- 8309742
TI  - Resistive and elastic unloading to assist spontaneous breathing does not change
      functional residual capacity.
AB  - Resistive and/or elastic unloading (a negative ventilator impedance, otherwise
      termed proportional assist ventilation) may be a useful means to assist
      spontaneous breathing. This only applies if the ventilator accurately provides
      pressure changes at the airway opening (P(ao)) proportional to the instantaneous
      flow and/or volume signal of spontaneous breathing and no significant phase lag.
      We designed such an infant ventilator, which controls the P(ao) by a negative
      feedback loop, and superimposes a second positive feedback circuit to generate
      unloading. To test this mode and the ventilator's accuracy in performing the
      synchronized pressure changes, we examined the functional residual capacity
      (FRC). We hypothesized that unloading by itself would not alter FRC because P(ao)
      should return to a preset baseline at end-expiration, and furthermore, that FRC
      could be actively altered by changing the baseline. Five anesthetized,
      tracheotomized, spontaneously breathing rabbits [respiratory system compliance
      22.4 +/- 4.6 mL/kPa (mean +/- SEM)] were exposed to end-expiratory P(ao) levels
      of 0, 0.2, 0.4, and 0.6 kPa. At each of these levels a period of regular
      continuous positive airway pressure (CPAP) was alternated with a period of
      unloading (-40 mL/kPa ventilator compliance combined with -3 kPa/L/s ventilator
      resistance). FRC measured by a sulfur hexafluoride washout technique was
      virtually identical on CPAP and during unloading at equal end-expiratory P(ao)
      (difference, 1.41% +/- 0.95%), but FRC increased upon elevation of the end
      expiratory P(ao) by 29.4 +/- 3.6 mL/kPa on CPAP and 30.2 +/- 3.2 at unloading
      (difference NS). We conclude that FRC is not destabilized by unloading, but that
      during unloading, as during CPAP, it depends on the end-expiratory P(ao).

PMID- 8309743
TI  - Lung function and bronchial challenges in infants: repeatability of histamine and
      comparison with methacholine challenges.
AB  - Limited information exists regarding the repeatability of lung function and
      bronchial challenge tests using the rapid thoracic compression technique (RTC) in
      infants. AIMS: To determine the repeatability of lung function and histamine
      challenge test results using the RTC technique and to compare the results
      obtained for bronchial challenges using histamine (H) and methacholine (M).
      METHODS: Twelve infants [7 healthy, 5 with cystic fibrosis (CF) had pairs of H
      challenges 1 week apart. Eleven infants (7 healthy, 4 CF) had one H and one M
      challenge a week apart. The provocative concentration of H or M to cause a 40%
      fall in maximum flow at functional residual capacity (PC40) was determined using
      the RTC technique. Twenty-three comparisons were possible between maximal
      expiratory flow at functional residual capacity (VmaxFRC) measurements made 1
      week apart. RESULTS: The mean difference between pairs of VmaxFRC measurements
      was 6.4% of baseline, and the coefficient of repeatability was 31.1% of baseline.
      The mean difference between PC40(H) measurements was 0.163 doubling
      concentrations, with a coefficient of repeatability of 1.66 doubling
      concentrations. The mean difference between PC40(H) and PC40(M) was 0.75 doubling
      concentrations, with 95% of PC40(H) between -0.18 to 1.69 doubling concentrations
      of the PC40(M). CONCLUSIONS: Although the repeatability of VmaxFRC using the RTC
      technique is less than for voluntary forced expiratory flow parameters in older
      children, similar results were obtained for infants as observed in older subjects
      for repeatability of H challenges and agreement between measures of bronchial
      responsiveness using H or M.

PMID- 8309744
TI  - Chronic interstitial lung disease in children.

PMID- 8309745
TI  - Comparison of helium dilution and nitrogen washout measurements of functional
      residual capacity in premature infants.
AB  - Comparison has been made of measurements of functional residue capacity (FRC) by
      a helium gas dilution (He) and a nitrogen washout (N2) technique. Twenty infants
      (median gestational age, 29.5 weeks) were studied at a median postnatal age of 25
      days. No infant was oxygen dependent. The coefficient of repeatability of FRC
      (He) was 6.4 mL/kg and of FRC (N2), 6.3 mL/kg. The coefficient of repeatability
      of the two methods combined was 13.8 mL/kg. In 10 infants the results of two
      techniques differed by more than 20% of the mean FRC; those infants were born at
      a significantly earlier gestation than the rest of the cohort (P < 0.01). We
      conclude that, except in very immature infants, techniques for measuring FRC (He)
      and FRC (N2) yield reproducible and comparable results in convalescent premature
      infants.

PMID- 8309746
TI  - Neonatal pulmonary vascular and parenchymal changes associated with arteriovenous
      malformation.

PMID- 8309747
TI  - Pulmonary oxygen toxicity: demonstration of abnormal capillary permeability using
      contrast-enhanced MRI.
AB  - An animal model of oxygen-induced pulmonary injury was used to assess the
      potential of contrast-enhanced MRI to identify and quantify abnormal capillary
      permeability. Sprague-Dawley rats were exposed to 100% oxygen for 48 h (n = 5) or
      60 h (n = 9). Axial spin-echo MR images were acquired in intubated, anesthetized
      rats with ECG-gating (TR 400; TE 6) immediately or 7 days after the cessation of
      oxygen exposure. Polylysine-Gd-DTPA, a macromolecular paramagnetic blood-pool
      marker, was then given intravenously and the lungs were serially imaged for 42 to
      47 min to monitor changes in signal intensity. Pulmonary enhancement was stable
      in rats exposed to 48 h of oxygen, and in rats exposed to 60 h of oxygen and
      given 7 days to recover. However, animals exposed to 100% oxygen for 60 h without
      a period of recovery showed a progressive increase in lung signal intensity for
      15 min after polylysine-Gd-DTPA. Pleural effusions also showed progressively
      increasing signal, reflecting a capillary endothelial leak. A two compartment
      model describing the kinetics of polylysine-Gd-DTPA in the plasma and
      interstitial water of the lung was consistent with the dynamic MRI data and
      allowed estimation of the fractional leak rate (0.235 min-1) of the contrast
      agent from plasma to interstitial water. Given the assumption of our kinetic
      model, MRI following intravenous administration of polylysine-Gd-DTPA can be used
      to quantitate changes in capillary integrity induced by hyperoxia, including
      acute capillary leakiness and return to normal endothelial integrity with
      recovery from hyperoxic injury.

PMID- 8309748
TI  - Doppler sonography in congenital ureteropelvic junction obstruction and
      multicystic dysplastic kidneys.
AB  - The accurate diagnosis of severe congenital ureteropelvic junction obstruction
      (UPJO) and the indications for surgical intervention are a matter of debate.
      Differential diagnosis from, for example, congenital cystic kidney malformations
      is important. In the present study we analysed the value of Doppler sonography
      (DS) for assessment of obstruction in congenital UPJO and its usefulness for
      differential diagnosis. A total of 138 infants and children were examined. Forty
      three healthy infants and 24 children who had had a pyeloplasty at least 1 year
      previously served as control groups. Seventy-one children with UPJO and cystic
      kidney malformations underwent DS in addition to the usual examinations of
      intravenous urography and scintigraphy. Resistive Index (RI) was measured in both
      kidneys. Twenty infants showed decompensated UPJO and had needed an operation.
      Preoperatively all showed significantly increased RI (RI = 74%), which returned
      to normal after operation (RI = 68.3%). Thirty-nine children with UPJO could be
      managed conservatively, showing compensated obstruction on diuretic renography.
      On DS they had normal and symmetrical RI values (RI = 67%). Eleven children had
      multicystic dysplastic kidneys; 4 underwent nephrectomy. On DS all showed either
      absence of perfusion signals or very low flow velocities with very high RI values
      (RI = 90-100%) in the renal vessels. One child was found to be suffering from a
      cystic nephroma. DS was able to reveal quite normal vessel distribution in renal
      parenchyma with slightly elevated RI values (RI = 80%). Our results indicate that
      DS a non-invasive, non-ionising method of investigation, may serve as an
      additional functional parameter for defining accurately the degree of obstruction
      in UPJO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309749
TI  - Intra- and interobserver variability in interpretation of DMSA scans using a set
      of standardized criteria.
AB  - A set of criteria was developed to standardize assessment of DMSA renal
      scintigraphy which were performed to evaluate children for acute pyelonephritis
      and renal scarring. This study was undertaken to assess intra- and interobserver
      variability in the interpretation of DMSA renal scintigraphy using these
      criteria. Renal contours and parenchyma were assessed in three zones. Contours
      were assessed as normal or abnormal and parenchymal defects were evaluated in
      terms of character, shape and degree in three regions (upper and lower pole and
      midzone). Two nuclear medicine physicians blindly reviewed 57 DMSA scintigraphy
      on two occasions each. Disagreement of each observer's evaluation of the same
      scintigraphy on two different occasions was described as intraobserver
      variability, and the comparison between readings by each of the two observers was
      described as interobserver variability. High levels of intra- (95.9% and 90.6%
      respectively, p < 0.05) and interobserver agreement (84.4%, p < 0.05) were
      demonstrated. There were minor differences in inconsistencies between the two
      kidneys or different kidney zones. We conclude that standardization of criteria
      resulted in higher intra- and interobserver consistency in interpretation of DMSA
      scintigraphy.

PMID- 8309750
TI  - Pseudotumoral cystitis.
AB  - Pseudotumoral cystitis is an unusual lesion and since it may be confused with
      rhabdomyosarcoma, knowledge of its existence is important. We report eight cases.

PMID- 8309751
TI  - Pediatric spinal bone marrow: assessment of normal age-related changes in the MRI
      appearance.
AB  - A retrospective study of 100 children (0-15 years) without known bone marrow
      abnormality, was performed to elucidate the spectrum of the MRI appearance of
      spinal bone marrow with age on T1-weighted images at 0.5 T. Fatty marrow
      distribution and vertebral signal intensity (SI) relative to disk SI were noted
      in each subject, and allowed the identification of distinctive patterns. The
      spinal marrow patterns and their relative frequency for different age groups were
      consistent with the known physiologic conversion from cellular to fatty marrow
      with age. Between the ages of 0 and 1 year, SI of corporeal ossification centers
      was similar or lower than SI of adjacent cartilage and disk in 87% of cases.
      Between the ages of 5 and 15 years, vertebral SI was higher than SI of adjacent
      disks in 90% of cases. A central or basivertebral zone of high SI consistent with
      focal fatty marrow was found in 16% and 31% of cases respectively. In conclusion,
      knowledge of these conversion patterns should serve as a practical aid in the
      interpretation of MRI examinations of the spine in children.

PMID- 8309752
TI  - Adrenal hemorrhage in infants undergoing ECMO: prevalence and clinical
      significance.
AB  - OBJECTIVE: To determine the prevalence and clinical significance of adrenal
      hemorrhage in infants undergoing ECMO therapy. METHODS: Prospective US evaluation
      of the adrenal glands was performed in 50 consecutive infants undergoing ECMO.
      The infants were examined at least every other day while on bypass. Adrenal
      hemorrhage was diagnosed at US examination when a suprarenal mass or adrenal
      gland enlargement was identified. RESULTS: Adrenal hemorrhage was identified in
      two infants (4%); one infant with septicemia, and one with primary pulmonary
      hypertension. Both hemorrhages were unilateral; one was right-sided, and one left
      sided. One hemorrhage occurred on the first day following the onset of ECMO and
      the other on the third day. The adrenal hemorrhage was not associated with an
      acute drop in hematocrit nor with adrenal insufficiency in either infant.
      CONCLUSION: Adrenal hemorrhage is uncommon in infants undergoing ECMO. When
      hemorrhage did occur in this series, it did not result in clinical complications.

PMID- 8309753
TI  - MR imaging of deferoxamine-induced bone dysplasia in an 8-year-old female with
      thalassemia major.
AB  - Bone changes in thalassemic patients receiving deferoxamine therapy for iron
      chelation include metaphyseal and growth plate irregularities. We present a case
      of an 8-year-old female with thalassemia major, who had magnetic resonance
      imaging after plain radiographs had shown metaphyseal changes in the distal
      femur. The signal characteristics of these abnormalities were consistent with
      hyaline cartilage; the surrounding marrow showed no evidence of iron overload.

PMID- 8309755
TI  - Gray-scale sonography in torsion of the testicular appendages.
AB  - The reliability of gray-scale ultrasonography in diagnosing torsion of the
      testicular appendages was studied in a series of 54 boys with acute non-traumatic
      scrotal pain. All boys were operated upon, and the appendages extirpated
      irrespective of their appearance at exploration; the final diagnosis was based on
      histological examination. Forty-two boys had appendicular torsion, 2 had
      testicular torsion and 10 had other diagnoses. Using the sign of appendicular
      torsion--an echogenic extratesticular structure situated between the head of the
      epididymis and the upper pole of the testis--as the criterion, 37 displayed a
      true positive, 9 a true negative, 3 a false positive and 5 a false negative
      diagnosis. Thus, the sensitivity was 88%, the specificity 75% and the positive
      predictive value 93% respectively. The echogenic mass varied in size from 3 to 17
      mm in diameter. In 34 of the 42 cases of appendicular torsion extratesticular
      fluid was present, and 19 patients showed enlargement of the head of the
      epididymis. It is concluded that gray-scale sonography is an accurate and
      valuable tool in diagnosing torsion of the testicular appendages.

PMID- 8309754
TI  - Spinal deformities in deferoxamine-treated homozygous beta-thalassemia major
      patients.
AB  - A new constellation of spinal changes are observed in homozygous beta-thalassemia
      major (HBT) patients receiving deferoxamine (DF), an iron-chelating drug used in
      combination with transfusion therapy in certain anemic syndromes. In a
      retrospective study of 22 HBT patients who were receiving DF therapy,
      morphological deformities (decreased spinal height, increased thoracic kyphosis,
      vertebral flattening and elongation anteriorly, and disk calcification) were
      found in 16 of 22 patients. These changes are believed to be caused by
      interference with spinal growth-plate development. Investigation of DF-dose
      correlation supports the conclusion that the spinal changes were DF-induced.
      Spinal changes observed in DF-treated patients differ both morphologically and
      pathogenetically from earlier reports of vertebral deformities occurring as a
      sequel to compensatory marrow hyperplasia in poorly transfused patients.

PMID- 8309756
TI  - Hepatobiliary sonography in cystic fibrosis.
AB  - Real-time abdominal sonograms of 27 pediatric patients with cystic fibrosis were
      reviewed to determine the frequency of hepatobiliary abnormalities and their
      variation with patient age. Attention was paid to hepatic echotexture and
      gallbladder size and contents. Seventeen patients (63%) had abnormal livers
      appearing as diffuse hyperechogenicity with loss of visualization of periportal
      echoes in 5 of 17 patients (29%), periportal hyperechogenicity in 9 of 17 (53%)
      and heterogeneity in 3 of 17 (17%). Gallbladder abnormalities, including a small
      gallbladder and sludge, were found in 9 patients (33%). Our findings show that
      altered hepatic echotexture is quite common in children with cystic fibrosis.
      Younger children tend to have diffusely hyperechoic livers, while older children
      often demonstrate periportal hyperechogeneity or diffuse hepatic heterogeneity.

PMID- 8309757
TI  - MRI appearances in amoebic granulomatous hepatitis: a case report.
AB  - Amoebiasis is a common cause of liver disease usually presenting as single large
      or multiple smaller abscesses. Cases with granulomatous hepatitis have rarely
      been described. We report the case of a 7-year-old girl with amoebic
      granulomatous hepatitis in which multiple liver abscesses were demonstrated by
      MRI. A total of 14 abscesses were identified, ranging from 5 mm to 3 cm in
      diameter. The largest lesions appeared to T2-weighted images as heterogeneous,
      low-intensity areas surrounded by a double-layered wall, the inner layer of which
      was hyperintense and the outer layer hypointense. These signs, which have never
      been described in classic amoebic abscess, represent, we believe, a pattern of
      hepatic granulomatous amoebiasis lesions. We suggest that MRI should always be
      performed in cases of amoebic infection.

PMID- 8309758
TI  - A new holder and surface MRI coil for the examination of the newborn infant hip.
AB  - A special holder was developed for examination of the infant hip joint using MRI.
      This holder allows the infant hip joint to be examined both in a neutral position
      and in various defined functional positions. A special integrated surface coil,
      also developed for this purpose, provides the high spatial resolution required
      for assessment of the fine joint structures. Thirty infants were examined and the
      new device has proved useful in advanced hip dysplasia, therapy-resistant
      subluxation and luxation, and for operative therapy planning (reconstruction of
      the acetabular roof, redirectional osteotomies). Interpretation errors due to
      misprojection can be eliminated to a large extent since the holder allows
      standardized and reproducible positioning.

PMID- 8309759
TI  - Multifocal thoracic actinomycosis simulating lymphoma.
AB  - Thoracic actinomycosis is rare in the pediatric age group. We report the unusual
      case of a 10-year-old girl who presented with prolonged fever and weight loss
      with a neck mass and multiple pulmonary nodules resembling lymphoma. Open lung
      biopsy confirmed the diagnosis of actinomycosis and the symptoms and signs
      improved after treatment with cephalosporin. The pathogenesis and radiographic
      manifestations are briefly discussed.

PMID- 8309760
TI  - Gorham's disease involving the thoracic skeleton. Plain films and CT in two
      cases.
AB  - Two cases of Gorham's disease (massive osteolysis, idiopathic osteolysis,
      vanishing bone disease) involving the thoracic skeleton are reported. Both
      patients were adolescent females with involvement of multiple ribs. Involvement
      of the thoracic spine and pleural effusions--unusual manifestations carrying a
      poor prognosis--were also present. The radiographic and computed tomographic
      appearances are included with discussion and review of this disease entity.

PMID- 8309761
TI  - Radiographic findings in 13q-syndrome.
AB  - Of 169 children with retinoblastoma treated at our institution between 1962 and
      1993, 5 had concurrent severe mental retardation, hypotonia, and abnormalities of
      constitutional chromosome 13. The associated skeletal abnormalities of these 5
      children are described and include delayed skeletal maturation, metaphyseal
      abnormalities, microcrania, facial bone abnormalities, and gracile long bones.

PMID- 8309762
TI  - Pediatric bladder outlet obstruction due to urethral calculus. Case report and
      review of the literature.
AB  - A case of urethral calculus in a child is presented. While there are several
      reviews of urethral stones from centers in Europe and Asia, a number of which
      include pediatric patients, we are not aware of descriptions of urethral calculi
      in childhood in patients in the United States or elsewhere in North America.

PMID- 8309763
TI  - Plain film identification of inverted Meckel diverticulum.
AB  - Inversion is a potentially serious complication of Meckel diverticulum. Since
      inversion provokes gangrene and small bowel obstruction, diagnosis by
      enteroclysis or imaging studies can conflict with the need for timely surgical
      intervention. We have noted that plain films may predict this lesion when a
      solitary mottled polypoid lesion occupies the ileum at the site of a small bowel
      obstruction.

PMID- 8309764
TI  - Carpal and tarsal osteolysis: an MRI, angiographic and histopathologic study.
AB  - The case of a 13-year-old girl with striking carpal and tarsal osteolysis
      (sporadic occurrence) is reported. MRI confirmed the total absence of carpal
      bones and medial tarsal bones. Dense fibrocollagenous tissue replaced the spaces
      left by the resorbed bones. Arteriography showed occlusion of the radial artery
      at the level of the physis of the distal radius with increased tortuosity of the
      ulnar artery. There was no major vascular occlusion in the foot except for some
      indistinct and blurred tarsal branches of the anterior tibial artery.

PMID- 8309765
TI  - Gradenigo syndrome: a case report.
AB  - The case is presented of a 13-year-old boy with recurrent episodes of otitis
      media who developed Gradenigo syndrome. Mastoid and petrous bone involvement were
      demonstrated by CT. Symptoms resolved with antibiotic treatment.

PMID- 8309766
TI  - Communicating bronchopulmonary foregut malformation associated with esophageal
      atresia and tracheo-esophageal fistula.
AB  - We report on two neonates who had esophageal atresia with a distal tracheo
      esophageal fistula (type III) and a second fistula between the distal esophagus
      and an intralobular sequestrated lung segment. In both patients the
      bronchopulmonary foregut malformation became evident only when the entire
      esophagus was in continuity following primary repair and a contrast swallow was
      performed to evaluate the anastomotic site.

PMID- 8309768
TI  - Lobar pneumonia: an ultrasound diagnosis.
AB  - Ultrasound was used to examine a 5-year-old girl with radiographic evidence of
      right upper lobe consolidation. The specific ultrasonic features of uncomplicated
      lobar pneumonia excluded other causes of consolidation.

PMID- 8309767
TI  - Unilateral perihilar opacification caused by lightning.
AB  - The chest radiographs of two children struck by lightning showed right perihilar
      opacification. The radiographs were taken 2 h and 5 h after the event
      respectively. To our knowledge no similar cases have been reported.

PMID- 8309769
TI  - Sonographic diagnosis of a huge necrotizing thymic cyst.
AB  - We report on a 10-year-old boy with a huge right-sided thoracic mass. The chest
      radiograph, ultrasonography CT and laboratory data were suspicious of an abscess
      forming pneumonia. Following unsuccessful antibiotic treatment the mass was
      surgically removed. Histological examination revealed a huge necrotizing thymic
      cyst.

PMID- 8309770
TI  - Ultrasound and MRI findings in a case of childhood amyloid goiter.
AB  - Goiter secondary to amyloidosis is rare in clinical practice and only a few
      descriptions of its radiologic features have been reported. We present the
      ultrasound and MRI findings of thyroid amyloidosis in a 7-year-old Turkish boy
      with familial Mediterranean fever.

PMID- 8309771
TI  - Sonographic diagnosis of pylephlebitis in children.
AB  - We present a case of inflammatory bowel disease in which the diagnosis of
      pylephlebitis was made by ultrasonography. The patient was treated with
      antibiotics and aspirin and had an uneventful recovery. The sonographic findings
      are described.

PMID- 8309772
TI  - Ascites produced by peritoneal seeding of neuroblastoma.
AB  - Preoperative CT and ultrasound of a 16-month-old girl with abdominal mass
      demonstrated the calcified mass and a copious amount of ascites. Pathological
      examination of the tumor revealed neuroblastoma, a tumor not usually associated
      with peritoneal seeding or ascites.

PMID- 8309773
TI  - Gyral calcifications detected on the 45th day after cerebral infarction.
AB  - The case is presented of a child with cyanotic congenital heart disease in whom
      middle cerebral artery stroke occurred, and consequently heavy gyriform
      calcification developed in the infarcted area within 45 days. To the author's
      knowledge, this is the shortest time interval within which such a calcification
      has ever been demonstrated.

PMID- 8309774
TI  - Iniencephaly: 3D-computed tomography imaging.

PMID- 8309775
TI  - CT evaluation of an eosinophilic granuloma simulating an aggressive rib neoplasm.

PMID- 8309776
TI  - Spondylometaphyseal dysplasia type VII.

PMID- 8309777
TI  - Are the pulmonary and aortic valves misnamed?

PMID- 8309778
TI  - M.P. Meza et al.: color flow imaging in children with clinically suspected
      testicular torsion.

PMID- 8309779
TI  - Calcium modulates the influence of length changes on the myofibrillar adenosine
      triphosphatase activity in rat skinned cardiac trabeculae.
AB  - The relationship between adenosine triphosphate (ATP) turnover and muscle
      performance was investigated in skinned cardiac trabeculae of the rat at
      different [Ca2+] and two different sarcomere lengths (1.8 microns and 2.2
      microns) at 20 degrees C. ATP turnover was measured photometrically by enzymatic
      coupling of the regeneration of ATP to the oxidation of reduced nicotinamide
      adenine dinucleotide. The trabeculae were studied under isometric conditions and
      when the length was altered repetitively at a frequency of 23 Hz, with a square
      wave, by 5% of the initial length. The isometric ATPase activity amounted to 0.48
      mM/s. Isometric ATP turnover and force were proportional at different [Ca2+].
      During length changes at maximal activation (pCa 4.27) and 2.2 microns sarcomere
      length, ATPase activity increased to up to 162% whereas at low [Ca2+], ATPase
      activity decreased with respect to the isometric value at that pCa. At pCa 5.5,
      ATPase activity was reduced to 33%. These results indicate that during the length
      changes the apparent cross-bridge detachment rate is increased and the apparent
      attachment rate is decreased. The findings suggest that the Fenn effect, i.e. the
      increase in energy turnover above the isometric value during shortening, is
      present in cardiac trabeculae at high levels of activation, but is absent or
      reversed at lower levels of activity.

PMID- 8309780
TI  - The role of the kidney in the development of hypertension: a transplantation
      study in the Prague hypertensive rat.
AB  - It has been shown that genetic hypertension in rats usually "travels with the
      kidney". To elucidate the mechanism of this phenomenon further, experiments were
      carried out in the Prague hypertensive (PH) rat, a model of genetic hypertension
      derived from the Wistar strain, in which a normotensive parallel, the Prague
      normotensive (PN) rat, was also bred from the same parent pair. Thus, it is
      possible to transfer organs between both parallels without substantial signs of
      rejection and without the use of immunosuppressive drugs. Unilateral nephrectomy
      and transplantation of one kidney between PH and PN rats, did not affect the
      arterial blood pressure (BP). Transplantation of one kidney from PN rats to
      bilaterally nephrectomised PH rats normalised the high BP. If a PH rat was left
      with one original kidney in situ after the transplantation of a "normotensive"
      kidney, the high BP persisted until the original "hypertensive" kidney was
      removed. This removal resulted in sustained normalisation of BP. When the
      development of high BP in the PH rats was prevented for 2 months after weaning by
      antihypertensive drugs, transplantation of kidneys from these rats to bilaterally
      nephrectomised PN rats always induced a sustained hypertension in the recipient.
      These results argue against a role of high-BP-induced damage to the kidney and
      against an intrinsic increase in the salt-reabsorptive capacity of the tubular
      epithelium in PH rats. The data support the view that the kidney from PH rats
      produces a "hypertensinogenic" substance, the secretion of which is genetically
      determined and is not influenced by the magnitude of the BP.

PMID- 8309781
TI  - Effects of ADH on the apical and basolateral membranes of toad urinary bladder
      epithelial cells.
AB  - Short-circuited urinary bladders from Bufo marinus were supported on their apical
      surface by an agar mounting method and impaled with microelectrodes via their
      basolateral membrane. This arrangement provided stable and long-lasting
      impalements of epithelial cells and yielded reliable membrane potentials and
      voltage divider ratios (Ra/Rb), where Ra and Rb are apical and basolateral
      membrane resistances respectively. The membrane potential under short-circuit
      conditions (Vsc) was -51.4 +/- 2.2 mV (n = 59), while under open-circuit
      conditions apical membrane potential (Va) and basolateral membrane potential (Vb)
      were -31.0 +/- 2.4 and 59.5 +/- 2.4 mV, respectively. This yields a "well-shaped"
      potential profile across the toad urinary bladder, where Va is inversely related
      to the rate of transport, Isc. Antidiuretic hormone (ADH) produced a
      hyperpolarisation of Vsc and Vb but had no significant effect on Va. In addition,
      Ra/Rb was significantly increased by ADH (4.6 +/- 0.5 to 10.2 +/- 3.6).
      Calculation of individual membrane resistances following the addition of
      amiloride showed that ADH produced a parallel decrease in Ra and Rb membrane
      resistance, with the observed increase in Ra/Rb being due to a greater percentage
      decrease in Rb than in Ra. The ability of ADH to effect parallel changes in
      apical and basolateral membrane conductance helps to maintain a constant cellular
      volume despite an increase in transepithelial transport.

PMID- 8309782
TI  - Basolateral mechanisms of intracellular pH regulation in the colonic epithelial
      cell line HT29 clone 19A.
AB  - The intracellular pH (pHi) of the colonic tumour cell line HT29 cl.19A was
      studied by microspectrofluorometry using the pH-sensitive dye BCECF. Single cells
      within a confluent monolayer, grown in a polarized manner on permeable supports,
      were examined. An amiloride-sensitive Na+/H+ exchange and a stilbene-insensitive
      Cl-/HCO3- exchange mechanism have been identified in the basolateral membrane.
      Removal of Na+ from the basolateral solution caused a decrease of pHi by 0.50 +/-
      0.09 unit (n = 4). Amiloride or Na(+)-free solution at the apical side had no
      effect on pHi. Cl- removal at the basolateral side led to an increase of pHi by
      0.20 +/- 0.03 unit (n = 4) whereas apical removal had no influence on pHi. This
      effect was independent of Na+ and was insensitive to 0.2 mM 4,4'
      diisothiocyanatodihydrostilbene-2,2'-disulphonic acid. A basolateral Cl-/HCO3-
      exchanger is the most likely explanation for this observation. The Na+/H+
      exchange mechanism in the basolateral membrane is an acid extruder, whereas the
      Cl-/HCO3- exchanger is an acid loader. Both of these mechanisms are important for
      the maintenance of intracellular pH in HT29 cl.19A cells.

PMID- 8309783
TI  - The time course of intracellular calcium movements in single human umbilical vein
      smooth muscle cells.
AB  - Intracellular Ca2+ ([Ca2+]i) was measured in single isolated human umbilical vein
      smooth muscle cells. Stimulation with histamine, in the absence of external Ca2+,
      mobilised Ca2+ from intracellular stores. When repeated brief applications of
      agonist were used, the time to onset, amplitude and rate of rise of the Ca2+
      transients were found to change. Two components could often be discerned in the
      rising phase of the transients, an initial slow "pacemaker" and a second faster
      and larger component. Following the first histamine-activated transient the basal
      level of [Ca2+]i was invariably lower than that prior to stimulation. This lower
      value was maintained whilst the cell remained in Ca(2+)-free solution, but could
      be returned to a higher level if the cell was exposed to external Ca2+. When the
      mobilisation of the intracellular store was reduced to undetectable levels, re
      exposure to Ca(2+)-containing medium reactivated responses. In the absence of
      external Ca2+, continuous application of histamine activated a series of
      transient increases in intracellular Ca2+, which decreased progressively in
      amplitude and rate of rise. The interval between transients also increased. These
      findings are discussed in terms of the activation of inositol trisphosphate
      sensitive intracellular Ca2+ stores and their sensitivity to cytoplasmic Ca2+ and
      intrasarcoplasmic reticulum Ca2+.

PMID- 8309784
TI  - Modulation by anions of p-aminohippurate transport in bovine renal basolateral
      membrane vesicles.
AB  - In the presence of 10 microM 2-oxoglutarate (2-OG) and of an inward Na+ gradient,
      uphill [3H]p-aminohippurate (PAH) uptake occurs due to cooperation of the PAH/2
      OG exchanger and the Na(+)-coupled 2-OG transporter in bovine renal basolateral
      membrane vesicles. Uphill PAH uptake is observed with Cl-, but not with gluconate
      as the bulk anion. To determine specificity and nature of this anion effect
      [3H]PAH uptake was measured in the presence of several anions without and with
      ionophores to distinguish indirect from direct effects on the PAH transporter.
      Na(+)-gradient plus 2-OG-stimulated [3H]PAH uptake is fast with Cl-, intermediate
      with F-, Br-, I-, NO3- and SCN-, and slow in the presence of gluconate, SO4(2-)
      and HPO4(2-). Stimulation by Cl-(as compared to gluconate) is attenuated but not
      abolished, by clamping electrical potential and pH differences to zero,
      suggesting a partial effect through charge compensation and a major effect of
      anions on the PAH transporter itself. Indeed, [3H]PAH/2-OG and [3H]PAH/PAH
      exchange rates under voltage- and pH-clamped condition depend on bulk anions
      although the anion effects are less pronounced than with Na(+)-gradient plus 2-OG
      stimulated [3H]PAH uptake. Since an inward Cl- gradient does not drive [3H]PAH
      above or below equilibrium distribution, Cl- ions are most probably not
      translocated by the PAH transporter. We propose that anions modulate the PAH
      transporter by interacting with a site not directly related to anion transport.

PMID- 8309785
TI  - The primary reflex effects of distension of the stomach on heart rate, arterial
      pressure and left ventricular contractility in the anaesthetized pig.
AB  - The present study was planned to investigate whether distension of the stomach
      primarily affects the heart rate, arterial blood pressure and left ventricular
      inotropic state and to explore the reflex mechanisms involved. In 16
      anaesthetized pigs, distension of gastric balloons with 0.81 of Ringer solution
      (gastric transmural pressure of about 13 mmHg) without controlling any
      haemodynamic variable caused an increase in arterial blood pressure. When this
      response was prevented, an increase in heart rate was obtained in each animal. In
      five pigs, the increase in heart rate was graded by step increments of
      distension. No significant changes in maximum rate of change of left ventricular
      pressure were observed in the sixteen pigs during gastric distensions performed
      whilst preventing changes in heart rate and arterial blood pressure. The
      responses of arterial blood pressure and heart rate were not influenced by the
      administration of atropine (four and six pigs respectively), while they were
      abolished by the administration of bretylium tosylate (ten pigs) and by bilateral
      vagotomy (six pigs; three cervical, three subdiaphragmatic). The present study
      showed that gastric distension which was likely to be innocuous in the
      anaesthetized pig reflexly increased arterial blood pressure and heart rate. The
      afferent limb of the reflex was in the vagal nerves and the efferent limb
      involved sympathetic pathways.

PMID- 8309786
TI  - Reactivity of the dog cavernous carotid artery. The role of the arterial and
      venous endothelium.
AB  - The cavernous carotid artery, that portion of the internal carotid artery that
      lies within the intracranial cavernous sinus, is covered by arterial (luminal
      surface) and venous (external surface) endothelium. The reactivity of the
      isolated canine, cavernous carotid artery, precontracted with 10(-5) M 5
      hydroxytryptamine, was studied by using in vitro perfusion and superfusion to
      evaluate the effects of vasoactive stimuli applied to the internal or external
      surface. Acetylcholine (10(-8)-10(-4) M), thrombin (0.01-1 U/ml) or calcium
      ionophore A23187 (10(-8) - 10(-6) M) on the luminal side produced concentration
      dependent relaxations which were reduced by the NO synthase inhibitor NG-nitro-L
      arginine methyl ester (L-NAME, 10(-4) M) or by removing either the internal or
      both endothelia. Thrombin or ionophore A23187 on the external side produced
      concentration-dependent contractions which were reduced by removing either the
      external or both endothelia, and by meclofenamate (10(-5) M). Acetylcholine on
      the external side, produced a concentration-dependent contraction that was
      unaffected by meclofenamate or by removing the external or both endothelia.
      Sodium nitroprusside (10(-7) - 10(-5) M) induced similar relaxation on both sides
      and regardless of whether the arteries were with or without endothelium. These
      results suggest firstly, that the cavernous carotid artery responds to
      acetylcholine, thrombin or calcium ionophore A23187 by relaxing or contracting
      when these agents act on the luminal or the external surface respectively.
      Secondly, the arterial endothelium mediates relaxation to these three substances
      by releasing NO, whereas the venous endothelium mediates contraction to thrombin
      and ionophore A23187 by releasing a cyclooxygenase product.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8309788
TI  - Influence of hepatic innervation on renal glomerular filtration rate.
AB  - Electrical stimulation of perivascular portal nerves leads to rapid, transient
      increase of renal glomerular filtration rate (GFR) and of urinary flow rate (V).
      In contrast, perivascular stimulation at the vena cava inferior does not
      significantly alter GFR and V. Spinal transfection at the thoracocervical
      junction does not significantly modify the effect of periportal nerve
      stimulation. Infusion of the alpha-adrenergic agonist phenylephrine (20 nmol/min)
      into the superior mesenteric vein increases GFR and V, whereas infusion of
      identical amounts of phenylephrine (20 nmol/min) into the jugular vein does not
      significantly alter GFR or V. The observations indicate that alpha-adrenergic
      innervation of the liver modifies renal function.

PMID- 8309787
TI  - Effects of training in normoxia and normobaric hypoxia on human muscle
      ultrastructure.
AB  - The adaptive response of skeletal muscle to training in normoxia and in severe
      normobaric hypoxia was studied. The first group of five male subjects trained for
      3 weeks on a bicycle (2 h/day, 6 days/week) in normoxia (Control training, Con
      T). A second group of five subjects trained in an ambient FIO2 decreasing
      progressively from 12.7% to a final level of 10.0% (hypoxic training, Hyp T).
      Fourteen months later, these subjects trained in normoxia at the same absolute
      power (normoxic training, Nor T). Peak oxygen consumption (VO2 max) was measured
      in normoxic and hypoxic conditions. Biopsies from the vastus lateralis muscle
      were analysed for fibre size, capillary and ultrastructural composition. Nor T
      had no effect on muscle tissue or VO2 max. Con T increased volume density of
      total mitochondria and lipids by 36 and 135% respectively (P < 0.05). Hyp T
      induced a 10% increase (P < 0.05) in peak VO2 max measured in hypoxia. Mean fibre
      cross-sectional area, interfibrillar mitochondrial volume density and capillary
      to-fibre ratio were increased (P < 0.05) by 10, 42 and 13% respectively in the
      Hyp T group. These results suggest that training at the same relative workload in
      normoxia and hypoxia have similar, but not identical, effects on muscle tissue.
      If training in normoxia is carried out at the same absolute workload as in severe
      hypoxia, no significant effects are observed.

PMID- 8309789
TI  - Effect of secretin and inhibitors of HCO3-/H+ transport on the membrane voltage
      of rat pancreatic duct cells.
AB  - The aim of the present study was to study the effect of secretin on the
      electrophysiological response of pancreatic ducts. Furthermore, we investigated
      the effects of lipid-soluble buffers and inhibitors of HCO3-/H+ transport. Ducts
      obtained from fresh rat pancreas were perfused in vitro. Secretin depolarized the
      basolateral membrane voltage, Vbl, by up to 35 mV (n = 37); a half-maximal
      response was obtained at 3 x 10(-11) mol/l. In unstimulated ducts a decrease in
      the luminal Cl- concentration (120 to 37 mmol/l) had a marginal effect on Vbl,
      but after maximal secretin stimulation it evoked a 14 +/- 2 mV depolarization (n
      = 6), showing that a luminal Cl- conductance (GCl-) was activated. The
      depolarizing effect of secretin on Vbl was often preceded by about a 6 mV
      hyperpolarization, most likely due to an increase in the basolateral GK+.
      Perfusion of ducts with DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic
      acid, 0.01 mmol/l) or addition of ethoxzolamide (0.1 mmol/l) to the bath medium
      diminished the effect of secretin. Acetate or pre-treatment of ducts with
      NH4+/NH3 (10 mmol/l in the bath) depolarized the resting Vbl of -65 +/- 2 mV by
      16 +/- 4 mV (n = 7) and 19 +/- 3 mV (n = 10), respectively. The fractional
      resistance of the basolateral membrane (FRbl) doubled, and the depolarizing
      responses to changes in bath K+ concentrations (5 to 20 mmol/l) decreased from 22
      +/- 1 to 11 +/- 2 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309790
TI  - Bisubstrates: substances that interact with renal contraluminal organic anion and
      organic cation transport systems. I. Amines, piperidines, piperazines, azepines,
      pyridines, quinolines, imidazoles, thiazoles, guanidines and hydrazines.
AB  - In order to evaluate whether N-containing substrates interact with the organic
      "anion" (p-aminohippurate, PAH) or only with the organic "cation" (N1
      methylnicotinamide, NMeN) transport system or with both, the stop-flow
      peritubular capillary microperfusion method was applied in the rat kidney in situ
      and the apparent Ki values of several classes or organic substrate against
      contraluminal NMeN and PAH transport were determined. Organic "anion" and organic
      "cation" transport are in inverted commas because neither transporter sees the
      degree of ionization in bulk solution, and they also accept nonionizable
      substrates [Ullrich KJ, Rumrich G (1992) Pflugers Arch 421:286-288]. Amines must
      be sufficiently hydrophobic (phenylethylamine, piperidine, piperazine) in order
      to interact with NMeN transport. Additional Cl, Br, NO2 or other electronegative
      groups render them inhibitory towards PAH transport also. Such bisubstrate amines
      were identified as follows: metoclopramide, bromopride, diphenhydramine,
      bromodiphenhydramine, verapamil, citalopram, ketamine, mefloquine, ipsapirone,
      buspirone, trazodone, H7 and trifluoperazine. Imidazole analogues interact with
      both transporters if they bear sufficiently hydrophobic alkyl or aryl groups or
      electronegative sidegroups. Bisubstrate imidazole analogues are tinidazole,
      pilocarpine, clonidine, azidoclonidine and cimetidine. Pyridines and thiazoles
      interact with the NMeN transporter if they have an additional ring-attached NH2
      group. Again with an additional Cl, Br, or NO2 group the aminopyridines and
      aminothiazoles also become inhibitors for the PAH transporter. Amongst the
      guanidines only substances with several electronegative side-groups such as
      guanfacine, amiloride, benzylamiloride and ranitidine, interact with both
      transporters. Amongst the phenylhydrazines only 4-bromophenylhydrazine interacts
      with the NMeN transporter and 4-nitrophenylhydrazine with both transporters.
      Quinoline (isoquinoline) and its amino and hydroxy analogues interact with both
      transporters, their pKa values correlate directly with the affinity to the NMeN
      transporter and reciprocally with their affinity to the PAH transporter. In
      experiments with labelled substrates only the sufficiently hydrophilic
      cimetidine, amiloride and ranitidine show a saturable transport, which can be
      inhibited by probenecid (apalcillin) and tetraethylammonium in an additive
      manner. The highly hydrophobic substrates verapamil, citalopram, imipramine,
      diltiazem and clonidine enter the cell very fast in an unsaturable and
      uninhibitable manner, apparently in the undissociated form, since N-methyl-4
      phenylpyridinium, which--disregarding its ionization--is similarly hydrophobic,
      shows a transport behaviour similar to that of tetraethylammonium [Ullrich et al.
      (1991) Pflugers Arch 419:84-92]. Ethidium bromide and dimidium bromide, which
      have a permanent cationic quaternary nitrogen and two sufficiently
      electronegative NH2 groups, also interact with both transporters.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8309791
TI  - Bisubstrates: substances that interact with both, renal contraluminal organic
      anion and organic cation transport systems. II. Zwitterionic substrates:
      dipeptides, cephalosporins, quinolone-carboxylate gyrase inhibitors and
      phosphamide thiazine carboxylates; nonionizable substrates: steroid hormones and
      cyclophosphamides.
AB  - In order to test what chemical structure is required for a substrate to interact
      not only with the contraluminal organic anion (p-aminohippurate, PAH)
      transporter, but also with the organic cation (N1-methylnicotinamide, NMeN, or
      tetraethylammonium, TEA) transporter, the stop-flow peritubular capillary
      perfusion method was applied and app. Ki values were evaluated. Zwitterionic
      hydrophobic dipeptides not only interact with PAH but also with NMeN transport
      although with lower inhibitory potency (Ki,PAH = 0.2-1.4; Ki,NMeN 6-14 mmol/l).
      Amongst the zwitterionic cephalosporins, which all inhibit PAH transport, the
      amino cephalosporin analogue cefadroxil was identified to interact also with NMeN
      transport (Ki,PAH = 3.0, Ki,NMeN = 11.2 mmol/l). All zwitterionic naphthyridine
      and oxochinoline gyrase inhibitors tested inhibit NMeN transport with app.
      Ki,NMeN values between 1.2 mmol/l and 4.7 mmol/l; the naphthyridine analogues
      show a good inhibitory potency against PAH transport (Ki,PAH approximately 0.4
      mmol/l), the piperazine-containing quinolone analogues have a moderate inhibitory
      potency (Ki,PAH = 1.1-2.5 mmol/l) and the piperazine-containing pipemidic acid
      did not inhibit PAH transport at all. Zwitterionic thiazolidine carboxylate
      phosphamides also interact with both transporters (app. Ki,PAH approximately 3.0;
      app. Ki,NMeN approximately 18.0 mmol/l). The nonionizable oxo- and hydroxy-group
      containing corticosteroid hormones also interact with the two transporters. (a)
      An OH group in position 21 is necessary for interaction with the PAH transporter,
      but not for interaction with the TEA transporter. (b) Introduction of an OH group
      in position 17 alpha abolishes interaction with the TEA transporter, but has
      different effects with the PAH transporter. (c) Introduction of an OH group in
      position 6 abolishes interaction with both, the PAH and the TEA transporter. (d)
      A change of the side-group in position 11 of corticosterone from -OH to -H to = O
      enhances interaction with the PAH transporter but has no effect on the
      interaction with the TEA transporter. Nonionizable 4- or 5-androstene analogues
      inhibit both transporters with app. Ki between 0.16 mmol/l and 0.64 mmol/l, if
      the steroids are soluble in a concentration greater than 1 mmol/l. Nonionizable
      oxazaphosphorins with more than one chloroethyl group interact with the PAH
      transporter with app. Ki between 0.84 mmol/l and 4.9 mmol/l and with the NMeN
      transporter with app. Ki between 3.2 mmol/l and 18.7 mmol/l. Thus a substrate
      interacts with both transporters if it is sufficiently hydrophobic, possesses
      acidic and/or electron-attracting plus basic and/or electron-donating groups, or
      possesses several electron-attracting nonionizable groups (O, OH, Cl). A certain
      spatial arrangement of the interacting groups seems to be necessary.

PMID- 8309792
TI  - Respiratory interneurons of the lower cervical (C4-C5) cord: membrane potential
      changes during fictive coughing, vomiting, and swallowing in the decerebrate cat.
AB  - The possible roles of interneurons in the C4-C5 cervical spinal cord in conveying
      central drives to phrenic motoneurons during different behaviour patterns were
      investigated using intracellular recordings in decerebrate, paralysed,
      artificially ventilated cats. Eleven cells were tentatively classified as
      respiratory interneurons since they: (i) could not be antidromically activated
      from the ipsilateral whole intrathoracic phrenic nerve, and (ii) exhibited large
      membrane potential changes during eupnea (7.3 mV +/- 3.6, range 2-13.5 mV) or non
      respiratory behaviour patterns. Six neurons depolarized in phase with phrenic
      discharge; four others depolarized during the expiratory phase; one neuron
      exhibited depolarization during the end of both expiration and inspiration. A
      variety of responses was observed during fictive coughing, vomiting, and
      swallowing. The results are consistent with C4-C5 expiratory interneurons
      conveying inhibition to phrenic motoneurons during different behaviour patterns.
      The responses of inspiratory and multiphasic neurons suggest that the roles of
      these interneurons are mode complex than simply relaying central excitatory or
      inhibitory drive to phrenic motoneurons.

PMID- 8309793
TI  - The ATP and Mg2+ dependence of Na(+)-K(+)-2Cl- cotransport reflects a requirement
      for protein phosphorylation: studies using calyculin A.
AB  - Na(+)-K(+)-2Cl- cotransport activity has previously been shown to depend on both
      intracellular ATP and Mg2+, but the mechanisms remain unknown. Cotransport in
      avian erythrocytes can be stimulated by a variety of agents including cAMP and
      permeant serine/threonine phosphatase inhibitors and is inhibited by prior
      depletion of either ATP with antimycin A, or mg2+ by incubation in A23187 plus
      EDTA. However, when cells were first stimulated with cAMP rather than calyculin A
      then subjected to either depletion strategy, a differential effect was found. The
      phosphatase-inhibitor-treated cells were resistant to subsequent ATP or Mg2+
      depletion while cAMP-treated cells were sensitive to both treatments. Parallel
      examination of protein phosphorylation confirmed that ATP or Mg2+ depletion leads
      to dephosphorylation of membrane proteins in cAMP-treated but not in calyculin-A
      treated cells. These results suggest that, for cotransport, ATP and Mg2+ are
      required primarily to maintain the system in a phosphorylated state rather than
      as direct modulators. The relative effectiveness of okadaic acid (EC50
      approximately 630 nM) and calcyulin A (EC50 approximately 8 nM) in stimulating
      the cotransporter indicate that a type-1 protein phosphatase is probably
      responsible for dephosphorylating the system. Cells stimulated by hypertonicity
      were also resistant to ATP or Mg2+ depletion suggesting that the mechanism of
      shrinkage-induced cotransport stimulation might also involve protein phosphatase
      modulation.

PMID- 8309794
TI  - Membrane-delimited activation of muscarinic K current by an albumin-associated
      factor in guinea-pig atrial myocytes.
AB  - Atrial myocytes obtained by enzymatic perfusion of hearts from adult guinea-pigs
      and cultured for 0-14 days were studied using different configurations of the
      patch-clamp technique. Activation of muscarinic K current [IK(ACh)] in whole-cell
      voltage-clamp mode by strongly diluted sera from various sources could be
      mimicked by corresponding concentrations of albumin, but not by delipidated
      ("fatty-acid-free") samples of albumin. In cell-attached membrane patches
      activity of IK(ACh) channels was significantly higher than basal IK(ACh) channel
      activity, if the pipette contained serum, whereas application of serum-containing
      solution to the cell outside the patch did not affect channel activity. In
      isolated inside-out membrane patches, strong IK(ACh) activation by internal
      guanosine triphosphate (GTP, 5 microM) was observed if the pipette contained
      serum. If no activator was presented to the outer face of the membrane, only weak
      opening activity was observed during bath application of GTP. These results
      demonstrate that the serum factor which causes activation of IK(ACh) is
      associated with albumin. Furthermore activation of IK(ACh) by that factor
      proceeds analogous to ACh or adenosine, i.e. via a membrane-delimited receptor, G
      protein, channel interaction.

PMID- 8309795
TI  - G(o) transduces GABAB-receptor modulation of N-type calcium channels in cultured
      dorsal root ganglion neurons.
AB  - High-voltage-activated (HVA) calcium channel currents (IBa) were recorded from
      acutely replated cultured dorsal root ganglion (DRG) neurons. IBa was
      irreversibly inhibited by 56.9 +/- 2.7% by 1 microM omega-conotoxin-GVIA (omega
      CTx-GVIA), whereas the 1,4-dihydropyridine antagonist nicardipine was
      ineffective. The selective gamma-aminobutyric acidB (GABAB) agonist, (-)-baclofen
      (50 microM), inhibited the HVA IBa by 30.7 +/- 5.4%. Prior application of omega
      CTx-GVIA completely occluded inhibition of the HVA IBa by (-)-baclofen,
      indicating that in this preparation (-)-baclofen inhibits N-type current. To
      investigate which G protein subtype was involved, cells were replated in the
      presence of anti-G protein antisera. Under these conditions the antibodies were
      shown to enter the cells through transient pores created during the replating
      procedure. Replating DRGs in the presence of anti-G(o) antiserum, raised against
      the C-terminal decapeptide of the G alpha o subunit, reduced (-)-baclofen
      inhibition of the HVA IBa, whereas replating DRGs in the presence of the anti-Gi
      antiserum did not. Using anti-G alpha o antisera (1:2000) and confocal laser
      microscopy, G alpha o localisation was investigated in both unreplated and
      replated neurons. G alpha o immunoreactivity was observed at the plasma membrane,
      neurites, attachment plaques and perinuclear region, and was particularly
      pronounced at points of cell-to-cell contact. The plasma membrane G alpha o
      immunoreactivity was completely blocked by preincubation with the immunising G
      alpha o undecapeptide (1 microgram.ml-1) for 1 h at 37 degrees C. A similar
      treatment also blocked recognition of G alpha o in brain membranes on
      immunoblots.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309797
TI  - The effect of tolbutamide on cerebral blood flow during hypoxia and hypercapnia
      in the anaesthetized rat.
AB  - The increase in blood flow in the cerebral cortex of the anaesthetized rat during
      hypoxia and hypercapnia was investigated. Cerebral blood flow (CBF) was measured
      using the hydrogen clearance method with acutely implanted platinum electrodes.
      Hypoxia (PaO2 35.3 +/- 2.4 Torr) and hypercapnia (PaCO2 68.1 +/- 5.1 Torr)
      increased basal CBF from 76.3 +/- 9.0 ml/100g/min to 168.1 +/- 20.1 ml/100g/min
      and 162.4 +/- 31.9 ml/100g/min respectively. The sulphonylurea tolbutamide (1mM
      in 1%DMSO) had no significant effect on CBF in hyperoxia or in hypercapnia.
      However, it attenuated the increase of CBF during hypoxia by 66 +/- 11% (p <
      0.01). This suggests that opening of tolbutamide-sensitive potassium channels may
      be involved in the process of hypoxic vasodilation in the rat cerebral cortex.

PMID- 8309796
TI  - Functional properties of mechanosensitive units from the chicken ureter in vitro.
AB  - A total of 66 mechanosensitive units was recorded from an in vitro preparation of
      the chicken ureter with attached nerves. They were classified into three groups
      according to their functional properties. U-1 units (30% of the units) responded
      to contractions of the ureter and exhibited very low spontaneous activity (mean:
      0.1 Hz). They had low average thresholds to distension (5.8 mmHg or 0.77 kPa),
      responded immediately to mechanical stimuli without exhibiting after discharges
      to strong stimuli. Their function might be the monitoring of peristalsis. U-2
      units (38%) did not respond to contractions and had irregular spontaneous
      activities (mean: 0.7 Hz). They exhibited a high average activation threshold to
      distension (42.6 mmHg or 5.73 kPa) and after discharges to strong mechanical
      stimuli. U-2 units might be involved in nociception. U-G units (32%) were
      characterized by their long-latency response to any mechanical stimulus used and
      had a regular high ongoing activity (mean: 2.2 Hz). The pressure thresholds cover
      the whole range of the U-1 and U-2 units (5 to 70 mmHg or 0.67-9.33 kPa) with an
      average of 31.5 mmHg or 4.2 kPa. The peak discharge to pressure stimuli occurred
      much later than in the U-1 and U-2 units and they exhibited pronounced after
      discharges. Some U-G units were inhibited by mechanical stimuli. U-G units had
      large receptive fields sometimes covering the entire ureter. The units responded
      to electrical stimulation of the ureter after a variable latency, indicating that
      they were synaptically driven. In addition, a late long-lasting response to
      electrical stimulation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309798
TI  - Making the invisible visible.

PMID- 8309799
TI  - Now is the time to advocate.

PMID- 8309800
TI  - Time to nurse: musings of an aging nurse radical.

PMID- 8309801
TI  - Methodological issues in a team approach to community health needs assessment.

PMID- 8309802
TI  - Men in nursing: a cautionary comparative critique.

PMID- 8309803
TI  - Victim blaming in nursing.

PMID- 8309804
TI  - Culturally competent health care.

PMID- 8309805
TI  - Infections of nonthoracotomy ICD leads: a note of caution.

PMID- 8309806
TI  - Alcoholism.
AB  - Several medications may help improve treatment of alcoholic patients. Medications
      that effectively and specifically reverse symptoms of alcohol intoxication or
      coma currently are lacking. Benzodiazepines remain the most effective medications
      for the treatment of alcohol withdrawal and for the prevention of withdrawal
      seizures and delirium, even though the adrenergic agents clonidine or atenolol
      may hasten resolution of withdrawal symptoms and facilitate outpatient
      detoxification. Psychosocial rehabilitation of alcoholics may be improved by
      judicious addition of the alcohol-sensitizing agents disulfiram and carbimide,
      the serotonergic drugs fluoxetine and buspirone, the opiate antagonist
      naltrexone, and, for primarily depressed alcoholics, tricyclic antidepressants.
      As in psychosocial alcohol rehabilitation, patient-treatment matching may improve
      results of pharmacotherapeutic intervention.

PMID- 8309807
TI  - Treatment of drug abuse syndromes.
AB  - This article serves as an introduction to the treatment of the various drug abuse
      syndromes. The theoretical concept underlying all diagnoses in drug dependence is
      presented first in detail, along with an extensive discussion of how these
      diagnoses are operationalized. Tolerance and dependence among the various drugs
      of abuse are considered. The review of treatment approaches divides drugs of
      abuse into pharmacologic categories and treatment into time segments, acute
      detoxification, intermediate-term, and long-term treatment. Pharmacotherapies for
      each of the categories of substance abuse and for each of the time periods are
      presented in a treatment-oriented fashion. Drug substitution therapy is
      considered. Individual and group therapy are discussed, as is education in the
      form of group process and peer feedback. The role of peer support groups is
      stressed. Finally, patient placement criteria across levels of care are
      explained.

PMID- 8309808
TI  - Differential diagnosis and psychopharmacology of dual disorders.
AB  - There are multiple potential interactions of substances of abuse with psychiatric
      illnesses. The individual agents, the stage of abuse, withdrawal, or recovery,
      and the patient's psychiatric illness must be considered as an integrated whole
      to ascertain the appropriate interventions. Polysubstance abuse can cause still
      more complicated interactions. Assessment of differential treatment needs for
      both the psychiatric illness component and the substance use disorder component
      permits both elements to be approached, often simultaneously, and can facilitate
      treatment of both. Ignoring either component can lead to inappropriate treatment
      or exacerbation of illness. The high rate of comorbidity of chemical dependence
      and other psychiatric illnesses is intriguing in light of studies that
      demonstrate vulnerability to drug abuse associated with specific alleles of the
      dopamine D2 receptor gene in some families. It is hoped that further
      investigations will shed light on the complex interactions and associations
      between chemical dependency and other psychiatric illnesses and result in new
      treatment strategies for both. In the past, many substance abuse treatment
      programs used to emphasize the complete cessation of all medications including
      some potentially beneficial prescription medications. This was likely because of
      previous excessive prescription by physicians of sedatives or benzodiazepines.
      Increasingly, recovery programs support intelligent, responsible use of
      nonaddictive psychiatric medications, and AA World Services prints a pamphlet
      supporting such physician-supervised use. Conversely, psychiatrists previously
      frequently overlooked or neglected diagnosis and treatment of chemical-dependency
      disorders. Greater efforts are needed to focus equal energy on diagnosis and
      treatment of chemical-dependency disorders in "psychiatric" populations. Many
      studies show that physicians neglect to collect adequate information and are not
      sufficiently aggressive in referring patients to chemical dependence treatment
      programs. By combining knowledge and appropriate therapeutic interventions from
      both psychiatric and addiction treatment fields, the needs of the dually
      diagnosed patient can be met more adequately.

PMID- 8309809
TI  - Psychopharmacologic treatment of panic, generalized anxiety disorder, and social
      phobia.
AB  - The anxiety disorders discussed in this article are common, affecting 5% to 10%
      of the general population. They may cause significant distress and disability and
      are often complicated by substance abuse and depression. Fortunately, these
      disorders can be treated successfully in the majority of patients, with
      alleviation of the most distressing symptoms and significant improvement in
      occupational and social functioning. Systematic research studies during the past
      decade have identified both specific medication-responsive anxiety syndromes and
      a variety of psychopharmacologic agents effective in their management.
      Psychopharmacologic treatment, often in combination with cognitive-behavioral
      therapies, can be tailored for the individual patient based on that patient's
      specific anxiety syndrome, comorbid disorders, and vulnerability to side effects.
      Careful monitoring of target symptoms can be used to assess the efficacy of
      treatment. Future research will help to develop new classes of antianxiety agents
      for currently treatment-resistant patients, and to investigate further the
      necessary duration of psychopharmacologic treatment.

PMID- 8309810
TI  - Post-traumatic stress disorder.
AB  - In the past few years, there has been a growing interest in the neurobiology of
      PTSD. A number of models have been proposed including possible structural
      changes. We have now seen the appearance in the literature of controlled and
      double-blind trials. Of interest are positive outcome studies associated with the
      use of drugs with serotonergic actions for a period of 8 weeks. Symptom relief
      provided by pharmacotherapy enables the patient to participate more thoroughly in
      individual, behavioral, or group therapy.

PMID- 8309811
TI  - The psychopharmacology of obsessive compulsive disorder. Implications for
      treatment and pathogenesis.
AB  - Recent advances in the pharmacotherapy of obsessive compulsive disorder (OCD)
      have led to a significant reduction in suffering and a return to productive
      living for many patients previously considered refractory to treatment. Potent
      inhibitors of 5-hydroxytryptamine (5-HT) re-uptake clearly have been established
      as the first-line pharmacotherapy for treatment of OCD. The addition of agents
      that enhance 5-HT neurotransmission to ongoing treatment in patients whose OCD is
      refractory to 5-HT re-uptake inhibitors has not yielded impressive results. The
      addition of dopamine (DA) antagonists to the regimens of treatment-resistant
      patients appears to be a potentially useful strategy for the specific subgroup of
      OCD patients with a comorbid chronic tic disorder such as Tourette's syndrome.
      Pharmacologic studies suggest that both the 5-HT and DA systems may be critical
      to the treatment and possibly the pathophysiology of OCD.

PMID- 8309812
TI  - Psychopharmacology of disorders in children.
AB  - Several features of pediatric pharmacology applied to psychiatry were mentioned
      throughout this review. The use of medications in young children requires
      attention to nuances of informed consent because of limited data and many
      potentially beneficial, possibly safer medications that are not approved for
      children. Children more rapidly metabolize and eliminate medications. They differ
      in sensitivity to main effects and side effects of a variety of medications.
      Therefore, it is important to start low and aim for the lowest effective dose.
      Ultimate doses may be higher, split and frequent doses may be necessary, and both
      clinical and laboratory follow-up may need to be more frequent. Finally,
      childhood onset of psychiatric disorders, similar to pediatric experience with
      diabetes or rheumatoid arthritis, frequently confers devastating stress and
      chronicity. The child's physician shares the frustration of poor treatment
      response or responses that cannot be sustained in a developing, dependent
      organism with a more aggressive variant of a disorder and an inevitably longer
      course. Despite a heartening increase in pediatric psychopharmacology interest
      and knowledge, much remains to be learned.

PMID- 8309813
TI  - Pharmacotherapy of disorders of adolescents.
AB  - Despite the increase in the diversity of Axis I disorders that can appear during
      adolescence, the psychopharmacology treatment literature is just now focusing on
      their special needs and response patterns. Several findings, such as the secular
      increase in suicide completion among male adolescents and the lack of controlled
      data showing tricyclic antidepressant efficacy in this age group, underscore the
      unique response of adolescents to drug treatment plans that have been successful
      with younger and older patients. The positive response to psychostimulants for
      adolescents with ADHD resembles that seen in younger children. On the other hand,
      the great increase in suicidal behavior, particularly overdoses, that occur in
      patients over 12 years of age makes the choice of a nonlethal (in intentional
      overdose) antidepressant a critical matter. Female patients who are younger seem
      to achieve higher blood levels than male patients, and also show more side
      effects for the same weight-adjusted dose. When one adds the developmental issues
      of this life stage, namely the need for separation and individuation, to the
      complications of prescribing medications, office practice and drug management
      become more complicated and require a strong therapeutic alliance to ensure good
      compliance. These issues make the use of psychotropic medications in adolescent
      patients challenging and complicated, but ultimately rewarding for those
      clinicians who can combine psychopharmacologic knowledge with good interpersonal
      therapeutic skills.

PMID- 8309814
TI  - Treatment of premenstrual mood symptoms.
AB  - For the sake of improvement in therapeutic approaches for women with cyclical
      menstrual symptoms, the presentation of premenstrual mood disturbances per se
      deserves specific consideration. Treatments studies for premenstrual mood
      symptoms have included conservative, supportive, nutritional, psychotropic,
      hormonal, and anovulatory measures. An analysis of the literature on premenstrual
      mood symptoms suggests that a rational schemata for diagnosis can yield a
      hierarchy of selected individualized treatments based on minimizing the
      intervention necessary for effective relief.

PMID- 8309815
TI  - Insomnia and related sleep disorders.
AB  - Insomnia may result from a variety of causes, including pathophysiology of the
      cardiorespiratory system, medical or psychiatric disorders, medications,
      substance abuse, and circadian rhythm disturbances. When these many causes are
      excluded, there remains an interesting group of patients whose disorder is
      characterized either by learned sleep-preventing associations or by a
      dissociation between physiologic measures and the subjective experience of sleep.
      One approach to understanding the latter group is to examine the patient's
      perception of the experience of being awake or asleep as well as the effects of
      hypnotic medication on this process.

PMID- 8309816
TI  - [The doctor in the eyes of his patients. Human values of medicine and at the
      threshold of the XXI century. Physician-patient relations].

PMID- 8309817
TI  - [Activity of bactericidal peripheral granulocytes in blood of workers employed in
      production of ferromanganese alloys].
AB  - We estimated bactericidal activity of peripheral blood neutrophils, using
      nitrotetrazolium blue reduction test (NBT), in metallurgists producing
      ferromanganese alloys. We didn't find essential changes in neutrophils metabolic
      activity in metallurgists comparing with the control group. Only spontaneous
      reduction index mean values were lower in metallurgists working over 10 years,
      and higher in metallurgists who smoked more cigarettes. Chronic bronchitis
      increased the index of stimulated reduction NBT.

PMID- 8309818
TI  - [Nephrotoxic action of cadmium].
AB  - Functional state of kidney in persons exposed to cadmium (Cd) is estimated mostly
      by determination of low molecular proteins in urine (beta 2MG, RBP) they are
      sensitive but not specific indicators of Cd exposure effects. The usefulness of a
      new indicator of renal functional disorders which is similar to metallothionein
      was studied. The test involved the determination of the urinary excretion of
      cadmium bound to low molecular specific protein. It was assessed in population
      exposed to cadmium in industry (high cadmium concentration) and in population
      limited to the conditions of residential area (low cadmium concentrations). It
      was found, that CdBP excretion in urine was higher in a group of persons exposed
      to cadmium with renal dysfunction (regardless of level of exposure). This was
      closely correlated with beta 2MG and levels in urine. People with renal
      dysfunction,-unexposed to cadmium have not excreted any CdBP in urine.

PMID- 8309819
TI  - [Migration of selected heavy metals in a water environment].

PMID- 8309820
TI  - [Activity of erythrocyte glucose-6-phosphate dehydrogenase in men occupationally
      exposed to asbestos].

PMID- 8309821
TI  - [Some parameters of Guerin cancer growth after exposure to Pielik (sodium salt of
      2,4-dichlorophenoxyacetate)].
AB  - Herbicide Pielik (sodium 2,4-dichlorophenoxyacetate) was tested with the aid of
      Guerin cancer animal model in 129 Wistar rats. An effect of this herbicide on the
      cancer growth dynamic (size and weight of the tumor), its malignancy (lymphatic
      nodes involvement), tumor-dependent animal cachexia (real body weight), and
      survival of rats depending on exposure period have been analysed. Aqueous
      solution of the herbicide was administered to animals of groups II, IV, V, and VI
      in the dose of 200 mg/kg body weight daily (1/3 LD50). Young rats were exposed to
      the herbicide during pre- and postnatal period till the death (groups III, IV and
      VI in the 80th day of life. Exposure to the herbicide was continued. Rats of all
      groups were sacrificed in the 16th, 20th, and 42nd day after implantation of
      Guerin cancer. Eight animals of each group were kept alive to assess survival.
      Accelerated growth of the tumor was noted in the animals exposed to the herbicide
      for the prolonged period of time (before and after birth). The same daily dose
      administered to the animals after weaning and continued to the 16th, 20th, and
      42nd day of tumor development (group IV) has not significant effect on tumor
      growth rate. An increase in the incidence as well as earlier onset of metastases
      to auxillary and groin lymphatic nodes were seen in group VI in comparison with
      the control animals (group III).

PMID- 8309822
TI  - [Halogenated hydrocarbons in human milk].
AB  - The concentration of several chloro-organic derivatives as PBC, HCH isomers, HCB,
      and DDT and its metabolites was assayed in the human milk. Sixty two samples
      collected from 15 human milk donors from Warsaw and surroundings were studied.
      The results show, that PCB is present in the most elevated concentration in
      comparison with the remaining compounds (mean 0.0241 mg/dl of milk or 0.723 mg/kg
      of fat). Substantial differences in halogenated hydrocarbons excretion with human
      milk were noted during lactation. However no correlation between the amounts of
      excreted fat and these compounds levels in the milk was seen. No tendency to the
      decrease of the excretion of assayed compounds with milk during lactation was
      observed.

PMID- 8309823
TI  - [Content of calcium and magnesium in daily food rations of children from two
      districts of southern Poland].
AB  - Calcium and magnesium content in daily diets for children of the range from 1.0
      up to 14.6 years was examined. Children from Bielsko districts lived in villages
      near Zywiec and from Katowice districts lived in the city of Bytom. Results are
      grouped according to: 1 domicile (city-village), 2 age range 1.0-1.5, 3.5-4.5,
      6.5-7.5, 11.4-14.6 years (in the range 11.4-14.6 also according to sex), and
      according to 3 qualitative evaluation of the diet (adequate, poor and
      inadequate). As can be seen from the presented results amounts of the two
      elements under study in the daily diets for children are incompatible with
      recommended nutritional standards. Discrepancies increased, when age of children
      was higher and when qualitative evaluation of the diet was poorer.

PMID- 8309824
TI  - [Epidemiology of mushroom poisoning in Poland].

PMID- 8309825
TI  - [Evaluation of plasmapheresis utility in treatment of poisoning with Amanita
      phalloides].

PMID- 8309826
TI  - [Mixed connective tissue disease in a male patient chronically exposed to toxic
      chemicals].
AB  - A case of the mixed disease of the connective tissue (MCTD) in male patient
      occupationally exposed to PVC and other toxic agents is presented. Clinical
      symptoms consisted of the typical signs of SLE, rheumatoid arthritis and lupoid
      hepatitis. MCTD diagnosis was confirmed serologically by the presence of
      autoantibodies anti-RNP. Prednisone administered in the daily dose of 60 mg
      produced remission.

PMID- 8309827
TI  - [Metabolism and toxic effects of methanol].

PMID- 8309828
TI  - [The role of estrogens in bone metabolism in women after menopause].
AB  - Mechanism of estrogens effect on bone metabolism in relation to postmenopausal
      period is discussed. An emphasis is on multiple effects of estrogens as both
      systemic and local factors. A role of progesterone and other gestagens in the
      process of bone remodelling is also stressed.

PMID- 8309829
TI  - [Prevalence and risk factors of osteoporosis in a population sample of Szczecin
      residents over 50 years of age].
AB  - The prevalence of osteoporosis and risk factors were evaluated in the random
      sample of Szczecin population aged over 50 years. Five hundred five individuals
      (273 women and 232 men) were examined. Risk factors for osteoporosis were
      evaluated with the aid of an questionnaire. Two X-ray pictures of both thoracic
      and lumbar spine were taken in the lateral position in all examined subjects and
      evaluated for osteoporosis. The most frequently encountered risk factors
      included: low physical activity (60% of women and 50% of men), tobacco smoking
      (43% of women and 79% of men), low consumption of the diary products in
      adolescence (53% of women and 49% of men), history of bone fractures, early
      menopause, and diabetes mellitus. The interpretation of X-ray findings showed
      that the incidence of osteoporosis was increasing with the age in both sexes, and
      was considerably higher in women. An analysis of the relationship between risk
      factors and radiological diagnosis of osteoporosis with chi 2 test showed that
      significantly higher incidence of the disease in women was associated with long
      term immobilization, low milk consumption, tobacco smoking, and early menopause.
      Osteoporosis in men correlated with only tobacco smoking.

PMID- 8309830
TI  - [Evaluation of bone mass in children in a national sample of the population].
AB  - Dual energy X-ray absorptiometry (DEXA) was used to measure a mean bone mineral
      density (BMD) and bone mineral content (BMC) in total body and lumbar spine (L2
      L4--BMD; L2-L4--BMC) in a group of 306 healthy children of both sexes, aged
      between 6 and 18 years. Step-wise increase in BMD in peripubertal age was noted.
      A degree of an increase in BMD at the age of 10 and 16 years was higher in boys
      than in girls. Bone mineral density of the spine was lower in the Polish
      population than that in USA. A high degree correlation between densitometric
      measurements and calendar age, and body height and weight was noted.

PMID- 8309831
TI  - [Dynamics of the course of idiopathic juvenile osteoporosis].
AB  - Clinical course of the idiopathic juvenile osteoporosis (IJO) was monitored in
      the group of 45 patients of both sexes with diagnosed disease, verified during
      follow-up period. The aim of the study was to evaluate the relationship between
      clinical symptoms and the results of biochemical, anthropometric, and
      densitometric measurements. An analysis of the obtained data enabled to
      distinguish the acute and chronic IJO phases. Evolution of the acute phase into
      chronic one was manifested by the cessation of pain and pathological gait
      stereotype, normalization of muscular strength, anthropometric parameters and
      urinary Pyr and DPyr excretion, as well as improvement in bone density.
      Hypercalciuria and increased urinary excretion of Pyr and DPyr, observed in the
      acute phase of IJO, may indicate that bone resorption exceeded bone formation.
      Tendency to maintain of alkaline phosphatase activity within lower limits of the
      normal values with slight increase during an improvement of densitometric
      parameters suggested transient osteoblast dysfunction.

PMID- 8309832
TI  - [Measurements of bone mineral density of the calcaneus in children with
      ultrasonic methods].
AB  - The study aimed at determining precision and accuracy of the ultrasound technique
      measuring bone mineral density in the calcaneus bone in children. Bone
      densitometer of Achilles type was adapted for measurements in children.
      Ultrasound beam was narrowed and a system of special pads positioning the foot
      were used for this purpose. Precision (CV (%) SOS: phantom 0.42, patients -0.42;
      BUA: phantom 1.46, patients -3.03) and accuracy of this technique were determined
      in comparison with dual energy X-ray absorptiometry as well as its value in
      diagnosis of osteopenia in childhood. An increase in SOS and BUA with the age was
      found. A decrease in these parameters was noted in children with osteopenia,
      comparing with the values in healthy children. Significant correlations (r
      ranging from 0.50 to 0.91) between ultrasound and DEXA techniques were seen. The
      results suggest that ultrasound technique might be useful in pediatric
      densitometry.

PMID- 8309833
TI  - [Evaluation of reproducibility and precision of ultrasonic measurements of the
      calcaneus for diagnosing osteopenia].
AB  - The study aimed at evaluating precision of ultrasound measurements of mineral
      bone density of the calcaneus, and evaluating correlation between the obtained
      results with those measured with single photon absorptiometry (SPA) and DEXA in
      different skeletal sites. In 24 healthy individuals and 44 patients with
      osteoporosis SOS, BUA, calcaneus stiffness index, spine bone mineral density (L2
      L4), femoral neck and calcaneal bone mineral densities were measured with DEXA
      technique whereas BMD in distal radial bone was measured with SPA. Very good
      precision of ultrasound measurements--better for SOS (CV = 0.12%), worse for BUA
      (CV = 1.64%) due to repositioning--was achieved. Statistically significant
      correlation between ultrasound and DEXA measurements of BMD in calcaneus bone (r
      = 0.90), and significant but worse correlations with BMD measurements for the
      spine (r = 0.43), femoral bone neck (r = 0.53), and 1/3 radius, (r = 0.51) were
      achieved. Ultrasound measurements of bone mineral density have low error of
      repeatability and good accuracy, enabling to discriminate healthy individuals
      from osteoporosis patients.

PMID- 8309834
TI  - [Analysis of risk factors and prevalence of spinal osteoporosis in a population
      sample of Warsaw residents over 50 years of age].
AB  - Vertebral fractures are the one typically seen in osteoporosis. An incidence of
      vertebral body fractures and risk factors for osteoporosis were analysed in the
      retrospective population based epidemiological study. Population sample included
      607 Warsaw inhabitants aged between 50 and 80 years (301 women and 306 men
      divided into age groups of 5 years, including approx. 50 subjects each).
      Vertebral body fractures were diagnosed on thoraco-lumbar spine X-rays made in
      the lateral projection. Risk factors for osteoporosis were analysed with the aid
      of an questionnaire. Bone mineral density was measured with dual energy X-ray
      absorptiometry and single photon absorptiometry in about 1/3 of the examined
      women. The prevalence of vertebral osteoporosis was high in both women (20.5%)
      and in men (27.8%). Low dietary calcium intake (below 800 mg daily) and low serum
      vitamin D levels (250HD less than 11 micrograms/ml) were characteristic for about
      90% of the examined population. In osteoporotic subjects the following risk
      factors were significantly more frequent: age (p < 0.01), tobacco smoking (p <
      0.001), low physical activity (p < 0.05), long-term immobilization (p < 0.01).
      Densitometry showed significantly lower bone mineral density in both women with
      vertebral fractures (p < 0.01) and low serum vitamin D levels (p < 0.05).
      Osteoporotic vertebral fractures were diagnosed more frequently in women with
      early menopause (p < 0.001). In the examined population there is a ligh
      prevalence of vertebral osteoporosis (predominating in mean) and risk factors.

PMID- 8309835
TI  - [Bone density in axial and peripheral skeleton and mineral density of the entire
      body as an age dependent factor in a population sample of healthy women].
AB  - Bone mineral density has been measured with dual energy X-ray absorptiometry
      (DEXA) in both axial and peripheral skeleton of 208 randomly selected healthy
      women aged between 20 and 80 years. Examined women have been stratified into the
      age groups of every 10 years. Bone mineral density has been measured in lumbar
      spine L2-L4 (AP), L2-L3 (Lat.) and proximal femur together with total body
      mineral density in every examined woman. The obtained results are considered
      reference values for the Polish population.

PMID- 8309836
TI  - [Pyridinoline and deoxypyridinoline excretion in urine of healthy children-
      dependence on age].
AB  - Pyridinoline (Pyr) and deoxypyridinoline (DPyr) are crosslinking compounds of
      bone collagen. Their urinary excretion is considered to be the first sensitive
      and specific marker of bone resorption in a number of metabolic bone diseases in
      adults. Application of crosslinks measurements to evaluate bone turnover rate in
      pediatric patients is so far limited because of lack of reference values.
      Therefore, the aim of our study was to determine urinary excretion of Pyr and
      DPyr in healthy children aged 3-18 yrs, and to evaluate the possible relationship
      between the levels of both compounds and body height, weight, BMC, and BMD. Pyr
      and DPyr levels were determined in first void urine samples obtained from 249
      children (124 boys, 125 girls). Urine aliquots were hydrolysed, Pyr and DPyr
      extracted on CF1 cellulose, and analysed by HPLC with fluorimetric detection.
      Bone mineral content (BMC) and density (BMD) were measured with Lunar DPX-L
      apparatus in 205 children (104 boys, 101 girls) from the same population, aged
      over 5.5 yrs. In prepubertal children, a tendency towards lowering of urinary Pyr
      and DPyr levels with advancing age was shown. At puberty, urinary excretion of
      both crosslinks markedly decreased. This phenomenon was observed at various
      calendar age in girls as compared to boys, reflecting sex-dependent differences.
      Significant negative correlation (p < 0.0001) between urinary Pyr and DPyr levels
      and calendar age, body height and weight, BMC and BMD, were also found. The
      obtained results suggest that references values for Pyr and DPyr excretion in
      growing children should be related to calendar age, sex, and--in case of
      adolescents--phase of puberty.

PMID- 8309837
TI  - [Transient osteoporosis of the hip].
AB  - Recently, more and more interest has been focused on the local bone lost, e.g.
      transient osteoporosis of the hip. It is believed that its etiology is similar to
      that Sudeck's disease. However, it is not clear, yet. Transient osteoporosis of
      the hip is more frequent in man than in women, at middle age as well as in the
      III trimester of pregnancy. The patients suffer from increasing hip pain without
      any definite cause. Laboratory findings do not show pathologies but X-ray reveal
      marked bone loss in the area of both the head and neck of the femoral bone with
      normal articular space. The symptoms disappear spontaneously within approximately
      few months, provided that no complications develop. At the same time, a normal
      bone structure in the proximal end of femoral bone is restored. The author
      presents a case of a 37-year old pregnant woman who suffered from rare
      complication of undiagnosed transient osteoporosis of the hip in the form of
      pathological compression fracture of the femoral bone neck, immediately below its
      head.

PMID- 8309838
TI  - [Diagnosis of osteoporosis].

PMID- 8309839
TI  - [Activation of osteogenic cells with polypeptide growth factors].

PMID- 8309840
TI  - [Treatment of osteoporosis].

PMID- 8309842
TI  - [The role of calcitonin in treatment of osteoporosis].

PMID- 8309841
TI  - [Rehabilitation procedures for osteoporosis in children: practical advice].
AB  - The authors, basing on their own experience, propose rehabilitation program for
      osteoporotic children. Such a program may restore basic locomotive system
      functions in the period of time up to 12 weeks. Efficacy of the proposed
      rehabilitation program was evaluated with orthopaedic examination, X-ray,
      densitometry, and biochemical measurements in 210 children of both sexes who were
      followed-up for 3 years. The program includes motoric rehabilitation with
      specifically designed exercises. Basic exercises include active exercises without
      loading, isotonic resistive exercises and exercises in water whereas auxiliary
      program includes relaxing and active-passive exercises. The authors discuss
      rehabilitation priorities in osteoporosis such as the use of analgesics and early
      erect positioning. An effective rehabilitation requires, however,
      hospitalization.

PMID- 8309843
TI  - [Epidemiology of proximal femur fracture and results of therapy in patients
      treated at the Orthopedic-Trauma Ward of the Railway Hospital in Warsaw in the
      years 1986-1990].
AB  - A retrospective analysis included 441 hospitalized patients with fractures of the
      proximal femoral bone, treated at the orthopedic-traumatology ward in 1986-1990.
      Such patients constituted 9.12% of all patients treated during those years. There
      were 313 women aged between 26 and 99 years (mean 77.4 years) and 128 men aged
      between 30 and 95 years (mean 68.3 years). Fractures were more frequent in women
      than in men (rate 2.4:1). Four hundred four patients (91.6%) were treated
      surgically. Mortality rate in this group was about 10% whereas in patients
      treated conservatively--approximately 66%. Locomotive functions were restored in
      the majority of patients under 80 years of age. Mean hospitalization time was 22
      days. Mean cost per patient in zlotys treated surgically was 4.97 million in
      1990, and 8.3 million in 1992.

PMID- 8309844
TI  - [Calcitonin in treating bone and joint lesions--clinical and experimental
      findings and personal experience].
AB  - Several experimental studies in the animal models and the use of calcitonin in
      patients with osteoarthritis, rheumatoid arthritis, and osteoporosis have shown
      multiple actions of this hormone, justifying its use in the wide range of
      osteoarthritic pathologies. We used well known animal models of tests to study
      chondro-tropic drugs such as: post-corticoid arthropathy, partial meniscectomy,
      immobilization of the lower extremity of rabbits, follow-up of the natural knee
      degeneration in the black mouse C57, and radiolabelled sulphates uptake by the
      cartilage, and have shown: (a) anticatabolic effect of salmon calcitonin as
      measured as GAG levels, width of articular space, and histochemical and
      morphologic examination of the cartilage in some model arthropathies, (b) anti
      osteoporotic properties counteracting an effect of corticosteroids, (c) increased
      uptake of sulphates by the articular cartilage of the rat following calcitonin
      administration in vivo. The studies explaining mechanisms of calcitonin actions
      included IGF-1 assays and beta-endorphins. The former increased transiently after
      calcitonin administration whereas the latter increased after non-steroid anti
      inflammatory agents use. Calcitonin decreased gastrin secretion with negligible
      effect on calcium ions and prostaglandin E2 levels in blood plasma while it
      potently acid secretion and increasing gastric mucus content in the stomach. The
      use of calcitonin in patients with arthrosis, rheumatoid arthritis, and
      osteoporosis with accompanying peptic and/or duodenal ulcers produced healing of
      peptic and/or duodenal ulcers in 75% of patients within 4 weeks with simultaneous
      shortening of the morning stiffness, increase in hand grip strength (in
      rheumatoid arthritis), and significant decrease in pain as well as an improvement
      in the quality of life in the majority of the treated patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8309845
TI  - Androgenic regulation of phosphorylation and stability of nucleolar protein
      nucleolin in rat ventral prostate.
AB  - Nucleolin is an abundant nucleolar phosphoprotein which has been implicated as a
      factor in various stages of ribosome synthesis, including transcription. Since
      androgens exert a profound effect on the rRNA synthesis in the target organ
      prostate, we have examined the nature of androgenic regulation of the amount and
      phosphorylation of nucleolin in this tissue. Phosphorylation of prostatic
      nucleolin is catalyzed in part by heparin-sensitive casein kinase 2 (CK-2) and by
      another (heparin-insensitive) protein kinase. Both the amount and phosphorylation
      of prostatic nucleolin are profoundly sensitive to androgens. Rapid reduction in
      the level and phosphorylation of nucleolin occurs following androgen deprivation,
      which corresponds to the ensuing cessation of prostatic growth leading to
      involution. Further, the loss of nucleolin phosphorylation and its degradation
      appear to be concordant. Administration of a single injection of 5 alpha
      dihydrotestosterone to castrated animals causes an early increase in the amount
      and phosphorylation of nucleolin, starting in the prereplicative phase in the
      prostatic cell nucleus. These data suggest that early androgenic regulation of
      nucleolin expression and phosphorylation may play a role in nucleolar control
      mechanisms relevant to prostatic cell growth.

PMID- 8309846
TI  - Plasma atrial natriuretic peptide concentration and renin activity during
      overhydration with 1.5% glycine solution in conscious sheep.
AB  - We estimated the changes of fluid compartment volumes and concomitant effects on
      plasma atrial natriuretic peptide (ANP) and plasma renin activity (PRA) for up to
      4 hr after intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min
      in six conscious ewes. Infusions of the same volumes of isotonic saline served as
      controls. Glycine infusions resulted in a four-fold increase and saline in a
      doubling of the plasma ANP concentration, despite a more pronounced volume
      expansion from saline. The ANP level remained significantly elevated for 2 hr
      after glycine infusion. This result suggests that glycine has a specific ANP
      stimulating effect which may contribute to the hypovolemia, hypotension, and
      natriuresis seen in the "transurethral resection (TUR) syndrome." The PRA
      decreased by about 50% in response to both infusions. However, PRA returned to
      the baseline level at the end of the glycine infusion, whereas it remained
      depressed during the entire follow-up period after saline infusion. This is in
      accordance with a pure volumetric influence on renin release, since calculations
      of fluid distribution between different compartments suggested that, in contrast
      to the effect of saline, only a small amount of irrigant water remained in the
      extracellular fluid after glycine administration. The urea and creatinine
      clearances increased only in response to isotonic saline. Glycine infusion was
      even followed by reduction of the creatinine clearance.

PMID- 8309847
TI  - Estramustine potentiates the effects of irradiation on the Dunning (R3327) rat
      prostatic adenocarcinoma.
AB  - The present study was designed to determine if estramustine phosphate (EMP) could
      potentiate the effects of irradiation on the Dunning (R3327) prostatic
      adenocarcinoma in rats. Two groups of male Copenhagen x Fisher F1 rats carrying
      bilateral tumors in the flank were used. Irradiation was given with a linear
      accelerator 6 MV, in a dose of 6 Gy/day for 4 days to the tumor on one side while
      the tumor on the other side served as control. EMP (360 micrograms/24 hours) was
      administered with osmotic pumps to one group of rats for 2 weeks, starting 1 week
      before irradiation. Tumor growth was calculated by measuring tumor volume, and
      tumor blood flow was measured 8 weeks after treatment. Irradiation alone
      effectively delayed tumor growth and EMP enhanced these effects. Tumor blood flow
      was stimulated by EMP treatment irrespective of radiotherapy. Volume density of
      tumor epithelium was effectively decreased by irradiation but no significant
      effects could be seen after EMP. In conclusion, the present study shows that EMP
      potentiates irradiation on rat prostatic adenocarcinoma, and further evaluation
      of this therapeutic approach in the clinical treatment of prostatic carcinoma is
      thus justified.

PMID- 8309848
TI  - Effects of chronic oral administration of a selective 5 alpha-reductase
      inhibitor, finasteride, on the dog prostate.
AB  - Young mature dogs received finasteride, a selective 5 alpha-reductase inhibitor,
      orally at 0, 5, 15, and 45 mg/kg/day for 27 or 53 weeks. The effect of
      finasteride administration on prostatic size and morphology was evaluated
      macroscopically and microscopically. Changes in glandular and fibromuscular
      compartments were quantitated by a point counting method on trichrome-stained
      sections. Finasteride administration induced a decrease of mean prostatic weights
      and epithelial atrophy in all treated groups. No changes in testicular weights
      and morphology were observed. The greatest prostatic shrinkage was obtained in
      the group receiving 45 mg/kg/day for 53 weeks; compared to placebo controls, the
      percent decreases in absolute volumes occupied by epithelium, lumens,
      fibrovascular stroma, and smooth muscle were 88, 97, 51 and 72, respectively.
      These results clearly demonstrate that prostatic shrinkage following finasteride
      administration results from a decrease in both glandular and fibromuscular
      compartments.

PMID- 8309849
TI  - [Gene therapy perspectives in cystic fibrosis].
AB  - Cystic fibrosis (CF) is a frequent autosomal recessive genetic disease. The
      isolation of the gene at the CF locus assigned to the long arm of chromosome 7
      band q 31 and defining description of its protein named CFTR (cystic fibrosis
      transmembrane conductance regulator) promoted understanding the basic biochemical
      defect. Brief review of relevant literature demonstrates that glycoprotein CFTR
      is a chloride channel and is activated by a combination of phosphorylation by
      protein kinase A and binding of ATP. Most common mutation of CF gene, a deletion
      of the three nucleotides encoding phenylalanine (Delta F508) results in
      disturbance of chloride transport through membrane of epithelial cells involved
      in pathomechanism of CF. The way for gene therapy in CF is open, however
      therapeutic progress is noted on both pharmacologic arena and on the gene cure
      front. Recombinant vectors utilizing the adenovirus system with high efficiency
      of CFTR gene transfer to airway epithelium demonstrated in a rat model look
      promising. The use of retroviruses for CFTR transfer is also advanced mode of
      somatic gene therapy. An alternative approach suggesting the use of germ line
      cells is prerequisite of the development of the preimplantation/preconception
      genetic CF diagnosis. A number of safety and efficacy issues have to be addressed
      for all approaches before human trials can be implemented.

PMID- 8309850
TI  - [Analysis of DNA adducts in molecular epidemiology of human neoplasms].
AB  - The techniques applicable for DNA adducts identification and quantitation are
      critically reviewed. The review also presents the data concerning an analysis of
      DNA adducts resulted from occupational exposure, tobacco smoking, diet and
      chemotherapy of tumors.

PMID- 8309851
TI  - [Mechanisms of cellular cytotoxicity. II. Cytotoxic factors of killer cells].

PMID- 8309852
TI  - [Role of melatonin in human physiology and pathology. II. Involvement of
      melatonin in pathogenesis of affective and chronobiological disorders. Melatonin
      and the aging process. Melatonin and neoplasms].
AB  - In the second part of this review the role of melatonin in pathogenesis of
      affective diseases and chronobiological disorders is discussed. Current views on
      melatonin involvement in aging are presented. Clinical experiments on the
      possible usefulness of melatonin in treatment of various types of cancers and
      hypothetical mechanisms of oncostatic influence of melatonin are also summarized.

PMID- 8309853
TI  - [Cathepsin D in diagnosis of neoplastic diseases].
AB  - The paper presents a review of results concerning the aspartic proteinase
      cathepsin D and its role in tumor invasion and metastasis. Special attention was
      paid to the clinical prognostic value of cathepsin D determination in the breast
      cancer cytosol.

PMID- 8309854
TI  - [Systemic vasculitis].

PMID- 8309855
TI  - Gout and 'pseudogout'. When are arthritic symptoms caused by crystal deposition?
AB  - The proper diagnosis of gout and pseudogout (ie, calcium pyrophosphate dihydrate
      crystal deposition disease) leads to correct treatment. The two disorders can be
      easily confused and misdiagnosed in certain situations. Thus, in every case,
      synovial fluid aspiration and microscopic synovial fluid analysis under
      compensated polarized light should be done to confirm the suspicion of crystal
      induced arthropathy. Underlying diseases should always be sought, because many
      are treatable.

PMID- 8309856
TI  - Obstructive sleep apnea. Treatment improves quality of life--and may prevent
      death.
AB  - Obstructive sleep apnea syndrome may be just an annoyance to an affected person's
      bed partner, or it can be a more serious and even dangerous condition for the
      person involved. One clue to the condition is daytime somnolence, although not
      all sleepy patients have the syndrome. If obstructive sleep apnea syndrome is
      confirmed by a polysomnogram, a trial of nasal continuous positive airway
      pressure (NCPAP) is warranted. If daytime somnolence is unaffected, then it is
      unlikely that the syndrome is the sole cause of the patient's sleepiness.
      Alternative diagnoses (eg, narcolepsy, atypical depression) should then be
      considered. Surgery, orthodontic devices, and pharmacotherapy are generally less
      effective than NCPAP and are usually reserved for patients who cannot tolerate
      NCPAP. Surgical techniques may be best suited for patients who have clearly
      defined craniofacial abnormalities and those who cannot tolerate NCPAP. Weight
      reduction to near ideal body weight and avoidance of benzodiazepines, opiates,
      and alcohol should be emphasized in all patients with suspected or confirmed
      sleep apnea.

PMID- 8309857
TI  - Complications of acute myocardial infarction.
AB  - Acute myocardial infarction is difficult enough to manage without the
      complications that commonly occur in the first days and weeks that follow. This
      article covers the most frequent complications, outlining when they are likely to
      occur, what the symptoms are, how they are best treated, and what sort of
      prognosis can be expected. In this way, the author provides a "map" of the days
      after infarction, showing the pitfalls and sand traps of clinical management.

PMID- 8309858
TI  - Attention-deficit hyperactivity disorder. Getting control of impulsive behavior.
AB  - A sizable number of school-aged children, more often boys, may have attention
      deficit hyperactivity disorder (ADHD). Its cause is unknown. Some investigators
      implicate food additives or lead poisoning. These theories are not supported by
      study results, however. Physicians are dependent on reports of parents and
      teachers to diagnose ADHD, since the children may not show signs at an office
      visit. The presence of criteria listed in the Diagnostic and Statistical Manual
      of Mental Disorders, third revised edition, and descriptions by parents and
      teachers of significant and pervasive impairment at home or school are
      diagnostic. Treatment is essential to minimize the academic failure, rejection,
      and loss of self-esteem that can result from the behaviors that typify ADHD. Use
      of stimulant medication is the most effective intervention and should be
      continued as long as it provides benefits without adverse effects. Concomitant
      behavioral therapy may be useful, and the entire family may benefit from
      psychotherapy.

PMID- 8309859
TI  - Oral empirical treatment of pneumonia. The challenge of choosing the best agent.
AB  - Knowledge of the respiratory pathogens that cause pneumonia, combined with data
      obtained from the initial history, physical examination, and laboratory studies,
      provides the framework for an empirical approach to the treatment of community
      acquired pneumonia. Selection of empirical therapy is based in large part on
      which of three broad groups the patient belongs to: previously well young adults,
      adults who are older or have a history of smoking or alcoholism, or HIV-infected
      adults. Several newer oral agents offer subtle advantages and disadvantages when
      compared with traditional agents, and these must be carefully weighed when
      prescribing treatment.

PMID- 8309861
TI  - Victory.

PMID- 8309862
TI  - Expanded roles for NPs and PAs?

PMID- 8309860
TI  - Peripartum complications. Hemorrhage, embolism, hypertension, and infection.
AB  - Maternal peripartum complications continue to be a significant problem in the
      United States, even among previously healthy women. The problems include
      peripartum bleeding, infection, hypertension, and thromboembolic disease. Primary
      care physicians are often called upon to treat these conditions. An awareness of
      the approach to diagnosis and management helps to ensure optimal outcome.

PMID- 8309863
TI  - Lipoproteins and apolipoproteins. Making use of their metabolic properties to
      individualize therapy.
AB  - Plasma contains four major lipoprotein particles: chylomicrons, VLDLs, LDLs, and
      HDLs. How cholesterol is metabolized depends on the particle with which it is
      associated. Thus, treatment for hypercholesterolemia is most effective when it is
      designed to fit the lipoprotein features of a given patient. Dr Kottke describes
      the five common forms of hyperlipoproteinemia and provides specific therapeutic
      approaches for each.

PMID- 8309864
TI  - Dyslipidemias in diabetic patients. Is standard cholesterol treatment
      appropriate?
AB  - Optimum care of diabetic patients should include screening for lipid
      abnormalities. The combination of high triglyceride and low high-density
      lipoprotein cholesterol levels, which is common in non-insulin-dependent (type
      II) diabetes, should be considered a separate risk factor for coronary artery
      disease. Pharmacologic therapy for dyslipidemias should be considered early in
      diabetic patients with atherosclerotic disease that has not responded to hygienic
      measures, including diet, exercise, and smoking cessation. Use of HMG-CoA
      reductase inhibitors and gemfibrozil (Lopid) may be more appropriate for
      treatment of diabetic dyslipidemias than niacin or bile acid-binding resins.

PMID- 8309865
TI  - Gastroesophageal reflux disease. Selecting optimal therapy.
AB  - An understanding of the pathophysiology of gastroesophageal reflux disease should
      aid selection of appropriate therapy. Symptoms of mild reflux disease may be
      controlled by traditional management (ie, elevating the head of the bed, dietary
      and other lifestyle changes, antacid use). These conservative measures also
      should be encouraged in patients with complicated disease. Prescription
      histamine2 (H2) receptor blockers remain the mainstay of antireflux medical
      therapy. Use of prokinetic drugs and H+,K(+)-ATPase inhibitors may be considered
      in refractory cases. A small percentage of patients may require antireflux
      surgery. If over-the-counter preparations of H2 blockers become available, they
      would likely become a popular component of conservative therapy.

PMID- 8309866
TI  - Our own organizations are campaigning for a healthcare bureaucracy. And you and I
      are paying for it!

PMID- 8309867
TI  - Multiphasic analysis of egg production in Japanese quail.
AB  - A multiphasic function that considers egg production of individual hens to result
      from more than one phase was used to describe egg production for Japanese quail.
      Each phase is determined by number of eggs within a clutch, including internally
      laid eggs, and pause between clutches. Cumulative egg production was fitted by
      using a function (Koops and Grossman, 1992) expressing time in terms of
      cumulative egg number. Data from nine hens over a 31-day period were analyzed to
      estimate parameters for lag and delay. The data were preadjusted for internal
      laying. Lag ranged from -1.14 to .19 h. Unlike chickens, there was no clear
      relationship between lag and average clutch length in Japanese quail. Average
      delay was about 21.6 h and seemed to be longer than that in the chicken.
      Furthermore, the residual standard error for delay was higher in Japanese quail
      than in the chicken.

PMID- 8309868
TI  - Realized heritability of tonic immobility in White Leghorn hens: a replicated
      single generation test.
AB  - Fearfulness was measured as latency to recover from induced tonic immobility
      using White Leghorn hens from a population originated by crossing three different
      strains selected for egg number and egg weight. Realized heritability was
      calculated in a single generation selection experiment with eight replicates,
      each consisting of 76 40-wk-old females from which 21% were selected for
      decreased tonic immobility duration. A randomly selected control population was
      maintained for each replicate. Separately from this experiment, fear differences
      between ages and sexes were investigated at 1, 2, 4, 8, 12, 16, 20, 24, 28, and
      32 wk. The realized heritability (.32 +/- .10) indicates that induced tonic
      immobility should respond to selection. It was numerically higher than the
      estimate calculated by half-sib analysis of variance in the base population (.18
      +/- .07); the logarithmic transformation did not yield higher heritability
      estimates. Crossing effects were evaluated in two different crossbreds, i.e.,
      Leghorn x Castellana and Buff Prat x White Prat, which suggested important
      negative heterotic effects for this fear-related trait (-31% and -54%,
      respectively). Significant (P < .05) quadratic and cubic variation between 1 and
      32 wk of age was obtained in females and males, respectively; the involvement of
      these age effects make it difficult to generalize about realized heritability for
      tonic immobility. Tonic immobility increased from 32 to 72 wk. Differences
      between the sexes were apparent, males showing longer tonic immobility durations
      than females except in the postjuvenile period before sexual maturity, suggesting
      a relationship between this trait and hormonal changes.

PMID- 8309869
TI  - Utilization of crude and refined palm and palm kernel oils in broiler diets.
AB  - Four experiments were conducted to evaluate the use of crude and refined palm
      (PAO) and palm kernel oil (PKO) in diets for broiler chickens. In Experiment 1,
      refined PAO and PKO were compared with corn oil (CO) and poultry oil (PO) at
      levels up to 10%. In Experiment 2, refined PAO and PKO were compared with PO at
      levels up to 8%. In Experiments 3 and 4, crude PAO and PKO were compared with PO
      at levels up to 8%. Diets were formulated based on the energy level assigned to
      PAO; other oils were added in amounts calculated to be isocaloric with an inert
      filler as required. Live production variables were measured. Samples of birds
      were processed to determine carcass characteristics, and fatty acid composition
      of adipose tissue was determined. In all studies, broilers fed crude or refined
      sources of PAO and PKO grew as well and utilized their feed as efficiently as
      those fed diets with isocaloric amounts of CO or PO. There were minimal
      interactions of source and dietary level of oil in any of the studies. Dressing
      percentage and quantity of abdominal fat were not influenced by source of
      supplemental oil; however, the fatty acid profile of adipose tissue was altered
      by the source of supplemental oil. There were only minor differences in fatty
      acid content of adipose tissue of broilers fed PAO (either crude or refined)
      versus those fed PO. However, increasing levels of PKO resulted in increased
      deposition of saturated fatty acids, especially lauric and myristic acid, and
      decreased concentrations of both monoenoic and polyunsaturated fatty acids. The
      resulting change in hardness of adipose tissue may prove to be advantageous in
      marketing.

PMID- 8309870
TI  - Growth, feed conversion, and carcass composition in females of four broiler
      crosses fed starter diets with different energy levels and energy to protein
      ratios.
AB  - Body weight, feed conversion, and carcass composition were studied in females of
      four commercial broiler crosses that differed in weight at 7 wk of age. The birds
      were fed starter diets for the first 3 wk containing different energy levels but
      the same protein level (Experiment 1) or varying energy or protein to equilibrate
      energy:protein ratios (Experiment 2). Experiment 1 was conducted in floor pens;
      Experiment 2 in batteries. All birds received a common grower diet from 4 to 7 wk
      of age. No significant cross by starter diet interactions were found for body
      weight, feed conversion, carcass weight, or protein percentages. In the floor
      experiment, 3- and 7-wk body weights were lower in birds receiving the highest
      energy starter than in those receiving lower energy starters; in the battery
      experiment, body weights were unaffected by energy of the starter. Feed
      conversion was lower in the birds receiving the high-energy starter in both
      experiments. Carcass weights essentially paralleled live weights in both
      experiments; however, percentage of protein in carcasses of 7-wk-old broilers was
      unaffected by starter diets. Feeding a high-energy starter for the first 3 wk
      posthatch resulted in higher carcass fat percentages at 7 wk of age but lower
      absolute and relative abdominal fat pad weights. The significant cross by starter
      diet interactions indicated that the fastest growing broilers responded to the
      high-energy starter diet by a significant reduction in abdominal fat without an
      overall reduction in carcass fat.

PMID- 8309871
TI  - Effect of early feed withdrawal on subsequent laying hen performance.
AB  - Two experiments evaluated the effects of short periods of feed withdrawal early
      in production on subsequent performance of laying hens. Laying hens of the H&N
      strain (22 or 20 wk of age) were full fed (control) or deprived of feed for 4 or
      7 days when they reached 10% production. Egg production was evaluated for 45 wk,
      but other performance data were collected for 32 wk because no treatment
      differences existed beyond that point. Feed withdrawal for 4 and 7 days caused BW
      losses of 14 and 20%, respectively. In Experiment 1 (winter), BW at 2-wk
      postwithdrawal for hens that did not eat for 7 days were reduced (P < or = .05)
      compared with controls or hens that did not eat for 4 days. However, in
      Experiment 2 (summer), BW of hens deprived of feed for 4 or 7 days were lower (P
      < or = .05) than those of controls. Average early egg weight (Weeks 1 to 6) was
      not different among treatments in both experiments. The only observed effect of
      treatment on long-term egg weight was that egg weight for 7-day hens was greater
      (P < or = .05) than for controls in Experiment 2. Early hen-day egg production
      was depressed by 4- or 7-day feed withdrawal, but long-term production was not
      different between control and 4-day hens in both experiments. However, hen-housed
      production was lower (P < or = .05) for 4-day hens compared with controls in
      Experiment 2. Fewer (P < or = .05) eggs were produced by 7-day hens versus
      controls in both experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309872
TI  - Ultrasonography as a tool for monitoring in ovo chicken development. 1. Technique
      and morphological findings.
AB  - Preliminary studies were performed to develop a method for using real-time, B
      mode ultrasonography (US) to directly image the internal morphology of the
      chicken egg and developing embryo. Different soft tissue interfaces will reflect
      US waves differentially. These reflected waves, or echoes are then converted into
      a two-dimensional image of internal morphology. A major limitation of diagnostic
      US is its inability to penetrate through gas or hard tissue (bone, shell)
      interfaces. Methodology development to overcome the acoustic obstacle presented
      by the eggshell and air cell constituted the initial part of the preliminary
      study. An acoustical window was achieved by creating a 2-cm fenestration through
      the large end of the eggshell, then filling the air cell with sterile saline.
      Morphological features of the yolk and embryo were recorded at 0, 2, 6, 9, 14,
      and 17 days of incubation. The second part of the preliminary study explores
      whether the acoustic window, once created, could then be closed, and if closed,
      whether egg viability could be maintained. A second concurrent trial was
      conducted with 32 eggs that were fenestrated, imaged, recorded, reclosed, and
      incubated. Two methods of closure were attempted: one using dialysis membrane and
      tape; the other using an eggshell allograft. Hatchability was partially retained
      with both window closure methods.

PMID- 8309873
TI  - Ultrasonography as a tool for monitoring in ovo chicken development. 2. Effects
      of eggshell alteration and ultrasonography on embryonic and posthatch
      development.
AB  - The influence of creating and closing acoustic windows on embryonic and posthatch
      development for the purpose of chicken embryogenesis monitoring by real-time
      ultrasonography (US) was evaluated at 2, 6, 9, 14, and 17 days of incubation.
      Acoustic windows were closed using either a porous dialysis film and tape (FM) or
      an eggshell allograft attached with collodion (CP). Results from eggs closed in
      each manner with and without concurrent nonsterile US examination were compared
      with two control groups. Window creation reduced hatchability. The hatchability
      reduction was caused primarily by bacterial contamination. Contamination was more
      common in the FM eggs than in the CP eggs and was greater in eggs that also
      underwent US. Hatchability increased and contamination decreased when US was
      performed closer to hatch. Egg weight loss was increased after Day 6 of
      incubation in FM + US eggs treated on Day 2 and after Day 9 in all eggs with
      windows except CP eggs treated on Day 9 and CP + US eggs treated on Days 6 and 9.
      Hatch weight decreased in chicks from eggs that had windows, particularly in FM
      eggs.

PMID- 8309875
TI  - Salmonella enteritidis immune leukocyte-stimulated soluble factors: effects on
      increased resistance to Salmonella organ invasion in day-old Leghorn chicks.
AB  - Cytokines, derived from either concanavalin A-stimulated Salmonella enteritidis
      immune chicken T lymphocytes [SE-immune Lymphocyte Stimulated Soluble Factor
      (LSSF)] or lipopolysaccharide-stimulated SE-immune chicken macrophages [SE-immune
      Macrophage Stimulated Soluble Factor (MSSF)], were evaluated for their ability to
      increase resistance to SE organ invasion in day-old Leghorn chicks. In Trial 1,
      day of hatch chicks were injected i.p. with either SE-immune LSSF or SE-nonimmune
      LSSF (control). In Trial 2, chicks were similarly injected with either SE-immune
      MSSF, SE-nonimmune MSSF, or SE-immune LSSF (positive control). Thirty minutes
      postinjection, all chicks were gavaged with an invasive dose of SE. Twenty-four
      hours later, livers and spleens from all chicks were cultured for SE. In Trial 1,
      SE-immune LSSF caused a rapid and marked protection (P < .01) against SE
      infection as determined by the number of chicks that were culture positive
      regardless of challenge dose. In Trial 2, SE-immune MSSF was not associated with
      protection against SE organ infection. These experiments demonstrate that SE
      immune LSSF, but not MSSF, are able to confer protection against SE organ
      invasion in day-old Leghorn chicks. Thus, it appears that the stimulated immune T
      cell, and not the macrophage, is responsible for producing the soluble products
      that protected the chicks.

PMID- 8309874
TI  - In vitro metabolism of radiolabeled carbohydrates by protective cecal anaerobic
      bacteria.
AB  - Cecal anaerobic bacteria from adult broilers were cultured in media containing
      .25% glucose or .25% lactose. Media also contained either [14C]-labeled lactose,
      glucose, galactose, or lactic acid as metabolic tracers. Cultures were analyzed
      at 4, 8, and 12 h for pH, radiolabeled and unlabeled volatile fatty acids, and
      lactic acid. The pH values of cultures containing .25% lactose were significantly
      (P < .05) higher than the pH values of cultures containing .25% glucose. Lactose
      cultures reached their lowest pH more slowly than glucose cultures.
      Concentrations of unlabeled volatile fatty acids increased and lactic acid
      decreased during incubation of the cultures. Radiolabeled sugars and lactic acid
      were more readily metabolized to volatile fatty acids in media containing lactose
      than in media containing glucose. The preferred metabolism of [14C]substrates,
      independent of media carbohydrate, was in the following order: lactic acid >
      galactose, lactose > glucose. The volatile fatty acids in which radiolabel was
      most concentrated were acetic acid, propionic acid, or butyric acid.

PMID- 8309876
TI  - Compromised antioxidant status associated with ascites in broilers.
AB  - Tissue infiltration by white blood cells in poultry with ascites has been
      reported, which could alter endogenous antioxidant status from oxidant stress.
      Therefore, the objective of this study was to determine the effect of ascites on
      ascorbic acid, tocopherol, and glutathione (GSH), which are major intracellular
      antioxidants. Broiler chicks (1 day) were placed in environmental chambers
      maintained with normal ventilation (Control) or under low ventilation, which
      produced a cumulative mortality of 31.3% due to ascites. At 3, 5, and 7 wk, lung
      and liver tissues were obtained from control birds (n = 5) and from birds in the
      low ventilation chamber with (ASC, n = 5) or without (NASC, n = 5) overt symptoms
      of ascites. There were no differences in tissue ascorbate, tocopherol, and GSH
      between the control and NASC groups with the exception of hepatic tocopherol at 7
      wk, which was higher (P < .05) in NASC birds than in ASC and control birds. In
      general, lung and liver concentrations of all three antioxidants were lower (P <
      .05) in ASC birds than in NASC and control groups. Uric acid, a product of purine
      metabolism, was lower (P < .05) in liver and lung in ASC birds at 3 wk compared
      with control birds. However, uric acid concentrations in ASC birds were higher (P
      < .05) in the lung and serum at 5 wk, and in the liver at 7 wk compared with NASC
      and control birds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309877
TI  - Effect of enzyme supplementation on the nutritional value of raw, autoclaved, and
      dehulled lupins (Lupinus albus) in chicken diets.
AB  - The effects of adding crude enzyme preparations to diets containing raw,
      autoclaved, and dehulled lupin seeds on the performance of broiler and Leghorn
      chicks (7 to 21 days) were evaluated in five experiments. In the first
      experiment, enzyme addition (combination of Energex-carbohydrase, Bio-Feed Pro
      protease, and Novozyme-alpha-galactosidase) to a diet containing 70% raw lupins
      improved the weight gain and feed to gain ratio of broiler chicks by 18 and 10%,
      respectively. The relative intestinal length and gizzard weight also were reduced
      by enzyme treatment. In the second experiment, the optimum concentration of
      enzymes was determined in diets containing 50% raw lupins. Bio-Feed Pro at 3%
      increased weight gains by 24% and the feed to gain ratio by 11%, whereas a
      combination of three enzymes at .10% of each yielded respective improvements of
      18 and 9%. In Experiment 3, the AME and protein digestibility of dehulled lupin
      seeds were increased by 18 and 7% compared with those for raw seeds. Autoclaving
      (20 min) significantly (P < .05) improved chick performance and AME and protein
      digestibility of raw seeds. In the fourth experiment, autoclaving (15 min),
      dehulling, and a combination of both improved weight gains by 11, 15, and 8% and
      feed to gain ratios by 4, 11, and 6%, respectively. Enzyme addition improved the
      performance of birds fed raw, but not autoclaved lupin diets. In the fifth
      experiment, dehulling and enzyme treatment but not autoclaving (20 min) improved
      the performance of birds fed diets containing 50% lupins. The relative weight of
      gizzard was reduced by both treatments but that of the pancreas was affected only
      by enzyme treatment. Overall, enzyme supplementation of raw lupin diets
      considerably improved chick performance. Dehulling of lupins also improved chick
      performance with results for autoclaved lupins being inconsistent.

PMID- 8309878
TI  - An investigation of the distribution of the protein content of samples of corn,
      meat and bone meal, and soybean meal.
AB  - This study examines the critical assumption of a normal distribution for protein
      content in feedstuffs. Data were collected from broiler feed mills on the
      nutrient content of corn, meat and bone meal, and soybean meal. Tests of
      normality for protein within each feedstuff were performed by each of two
      methods: 1) the Shapiro-Wilk test (n < 50) or Kolmogorov-Smirnov test (n > 50);
      and 2) the D'Agostino-Pearson K2 test. Results indicate that protein is non
      normally distributed in corn and in meat and bone meal, but protein is normally
      distributed in soybean meal.

PMID- 8309879
TI  - Effects of extrusion and expelling on the nutritional quality of conventional and
      Kunitz trypsin inhibitor-free soybeans.
AB  - Two chick growth experiments and a precision-fed cockerel digestibility assay
      were conducted to evaluate the effect of extrusion and expelling on the nutritive
      value of conventional (CSB) and Kunitz trypsin inhibitor-free (KFSB) soybeans. In
      the first experiment, performance of chicks fed CSB or KFSB autoclaved at 121 C
      was similar to that of chicks fed CSB or KFSB extruded at 138 C. The effect of
      extrusion temperature on protein quality of the soybeans was evaluated in the
      second experiment. Eleven corn-soybean diets were formulated to contain one of
      the following: CSB extruded at 104, 121, 138, or 154 C; KFSB extruded at 104,
      121, or 138 C; CSB extruded at 121, 138, or 154 C followed by processing through
      an expeller; and commercial dehulled solvent-extracted soybean meal (SBM). All
      diets contained 20% crude protein and the same amount of soybean oil and were fed
      to chicks from 7 to 21 days of age. The CSB extruded at 104 or 121 C and KFSB
      extruded at 104 C yielded depressed growth and feed efficiency compared with SBM.
      Performance of chicks on the other treatments was similar to that of chicks fed
      SBM. Pancreas weight (as a percentage of BW) decreased as extrusion temperature
      increased, with the response being greater for CSB. Growth performance was
      greater and pancreas weights were lower for chicks fed KFSB extruded at 104 or
      121 C compared with those of chicks fed CSB extruded at the same temperatures.
      Expelling improved weight gain and feed efficiency when CSB was extruded at 121
      C. A 48-h digestibility assay with cecectomized cockerels indicated that
      digestibility of amino acids in CSB and KFSB increased as extrusion temperature
      increased and that digestibilities of amino acids in CSB extruded at 104 or 121 C
      were lower than those in KFSB extruded at the same temperatures. Results of this
      study indicated that extrusion of CSB at 138 to 154 C or extrusion of KFSB at 121
      to 138 C yields protein quality similar to that of SBM.

PMID- 8309880
TI  - Nutritional evaluation of a copper-methionine complex for chicks.
AB  - Three chick experiments were conducted to evaluate a new Cu complex product, Cu
      Met. Relative bioavailability of Cu was assessed with two bioassay systems, one
      employing bile Cu concentration as the criterion at Cu-deficient levels and
      another employing liver Cu concentration at Cu-excess levels. Relative
      bioavailability of Met was assessed separately. Common-intercept multiple linear
      regression (slope-ratio) of bile Cu concentration or liver Cu concentration
      regressed on supplemental Cu intake was used to assess Cu bioavailability
      relative to the standard, analytical-grade CuSO4.5H2O, which was set at 100%. In
      addition, Cu-Lys and CuCl (compounds previously evaluated by bile Cu
      concentration) were evaluated by the liver Cu accumulation method. Relative
      bioavailability of Cu in Cu-Met was estimated as 96% by the bile Cu assay and 88%
      by the liver Cu assay, which were not different (P > .05) from 100%. The liver Cu
      assay estimated that relative Cu bioavailabilities in Cu-Lys and CuCl of 114 and
      145% (P < .05), respectively. These values were very close to those previously
      estimated by the bile Cu assay. Relative Met bioavailability of Cu-Met was 100%
      of the standard, i.e., feed-grade DL-Met.

PMID- 8309881
TI  - Effect of maternal dietary triiodothyronine on embryonic physiology of turkeys.
AB  - The objective of the present experiment was to feed triiodothyronine (T3) to
      lines of turkey breeders selected for egg production and growth, and an
      unselected control line. The data were collected to determine a genetic basis for
      thyroid-mediated maternal effects on embryonic physiology and livability. At 30
      wk of age, turkeys of the three lines were photostimulated and half of each line
      was fed a diet containing .5 ppm T3. Maternal dietary T3 increased egg weight,
      reduced yolk solids and eggshell conductance constants, and increased albumen
      solids and water in eggs in all lines compared with control eggs. Hatchability in
      all lines was not affected by the dietary treatment (Control = 72.2%; T3
      treatment = 70.7%), but there was a significant interaction between dietary T3
      and line of turkey for the time of embryonic mortality, time of hatching, and
      carbohydrate metabolism of the embryo. The T3 increased mortality of the Egg line
      and unselected line during pipping, increased mortality of the Growth line in the
      plateau stage, but decreased its mortality during internal pipping. Reduced
      glycogen in liver as well as a reduced gluconeogenesis were evident in embryos of
      the two selected lines fed T3. It is concluded that genetic lines may have
      different metabolic patterns based on their genetic constitution in order to
      compensate for variations in egg solids and eggshell conductance constants. The
      metabolic patterns are reflected in different levels of embryonic blood plasma
      glucose, glycogen, and gluconeogenesis.

PMID- 8309883
TI  - Factors affecting circulating growth hormone binding protein in chickens.
AB  - Growth hormone binding protein (GHBP) may be an important factor in the
      regulation of growth and might provide an indirect, relatively noninvasive means
      of predicting the status of hepatic growth hormone receptor (GHR) activity.
      Several factors have been reported to influence growth hormone (GH), GHR, or
      GHBP. Therefore, these studies were conducted to test how age, sex, nutritional
      status, and glucocorticoids (cortisone acetate, CA) influence serum
      concentrations of chicken GHBP. Serum GHBP activity was highest (mean percentage
      specific binding (%SB) = 12.43 +/- .80) at hatch and decreased linearly (P <
      .0001) to 5 wk of age (%SB = 1.99 +/- 1.13). There were no sex-related
      differences in serum GHBP activity from hatch to 5 wk of age (P > .08). Short
      term nutrient deprivation (24-h) of 4-wk-old broilers also had a significant
      effect on serum GHBP activity (P < .0001). Measurement of serum GHBP activity
      with refeeding (after a 24-h period without feed) restored %SB to normal values.
      Feeding broilers a low-protein diet (12% CP) did not significantly affect serum
      GHBP activity when compared with that of broilers fed a commercial broiler diet
      (23% CP; P > .30). Administration of cortisone (1, 5, and 10 mg/day), every 24 h
      for 7 days, had no effect, at any dose, on serum GHBP activity at 48 h and 1 wk
      after the last injection. These results indicate that serum GHBP activity is
      influenced by factors such as age and feed deprivation. It remains to be
      determined whether these changes in GHBP are associated with changes in GHR as
      reported for mammalian species.

PMID- 8309882
TI  - Immunohistochemical differentiation of gastrin and cholecystokinin in
      gastrointestinal tract of chickens.
AB  - The presence of cholecystokinin (CCK) in the gastrointestinal tract of chickens
      has not been well demonstrated, although immunological and chromatographic
      techniques have shown the presence of intestinal gastrin-CCK-like factors.
      Recently, a new peptide, structurally related to mammalian CCK, but with a
      gastrin-like activity, has been isolated from the digestive tract of chickens.
      The objective of this work has been: 1) to study the presence of gastrin-CCK-like
      immunoreactivity (IMR) in the digestive tract of chickens; 2) to distinguish
      chicken gastrin from CCK; and 3) to establish their distribution using specific
      antibodies. Tissue specimens from the proventriculus, gizzard, pylorus, duodenum,
      jejunum, ileum, ceca, and rectum were studied using indirect immunofluorescence
      procedures. The antibodies used were: 1) an antibody specific against the C
      terminal pentapeptide common to gastrin and CCK; 2) one specific against CCK-33;
      and 3) one specific against chicken gastrin. Their use allowed the
      differentiation of two cellular populations which showed different affinities for
      the antibodies, indicating the presence of a gastrin-like peptide in the antrum
      and another CCK-like peptide in the small intestine, with the highest
      concentration in the proximal ileum. Immunoreactivity was not found in any other
      studied area. Two different peptides of the gastrin-CCK family are present in the
      chicken's gastrointestinal tract. However their differentiation and
      identification are more difficult than in mammals due to the greater structural
      similarities of these peptides in birds.

PMID- 8309884
TI  - Research note: a modified most probable number technique to enumerate total
      aerobes, enterobacteriaceae, and Salmonella on poultry carcasses after the whole
      carcass rinse procedure.
AB  - A modified most probable number (MPN) technique utilizing a single 10-fold
      dilution series was tested to enumerate the microbiological population from the
      whole carcass rinse procedure for poultry. Diluent for the MPN series was a
      general nutrient broth. Resuscitation of damaged cells and pre-enrichment of low
      numbers of microorganisms was accomplished by the MPN media. The MPN dilution
      tubes positive for growth were used to calculate the total aerobic bacterial
      population. Subculturing with tetrathionate enrichment broth and subsequent
      plating to differential media were used to identify and enumerate Salmonella.
      Enterobacteriaceae were enumerated by subculture of the MPN positive tubes in
      brilliant green (BG) bile 2% broth supplemented with 1% dextrose that were then
      observed for gas production. The aerobic bacterial counts obtained by the
      modified MPN were similar, yet significantly higher than those obtained with the
      conventional plate count techniques (P < .05), and both were significantly higher
      than the three tube MPN counts.

PMID- 8309886
TI  - An open letter to public health nurses.

PMID- 8309885
TI  - Research note: the performance of spring- and summer-reared broilers as affected
      by precision beak trimming at seven days of age.
AB  - In each of two duplicate trials approximately 2,500 day-old Peterson x Arbor
      Acres straight-run broiler chicks were equally divided between two treatments of
      three pens each. Treatment 1 was maintained as controls (C), and Treatment 2
      birds were precision beak-trimmed (PBT) at 7 days of age. Feed and water were
      supplied for ad libitum consumption to both groups. Trials 1 and 2 were initiated
      in March and June, respectively. Performance of spring-reared broilers were
      comparable regardless of beak trimming procedure, except that PBT broilers
      experienced slightly higher mortality after PBT. Final body weights of the summer
      reared broilers were 15% lower than those reared in the spring. Additionally, PBT
      resulted in significantly reduced final body weights and feed intake. There were
      no significant differences in mortality or feed conversion due to PBT.

PMID- 8309887
TI  - One hundred years of powerful women: a conversation with Marguerite Cobb.
      Interview by Katherine Young Graham.

PMID- 8309888
TI  - One hundred years of powerful women: a conversation with Doris Roberts. Interview
      by Marla E. Salmon.

PMID- 8309889
TI  - A model for delivering culture-relevant care in the community.
AB  - The increase in cultural diversity of the urban populations of the United States
      is presenting a challenge for the delivery of culturally relevant care by
      community health care nurses. We developed a model for delivering such care built
      on key theoretical concepts derived from community health nursing, transcultural
      nursing, self-efficacy, and social support theories.

PMID- 8309890
TI  - The impact of organizational and environmental factors on staffing in home health
      care.
AB  - Home health care agencies are experiencing changes in staffing demands. I
      evaluated the staffing patterns of such agencies and investigated the impact of
      organizational and environmental factors on staffing. Disproportionate stratified
      random sampling, based on type and region of agency, was used to select Visiting
      Nurse Associations and hospital-based agencies. Seventy-three percent responded
      to the mail survey, 120 and 156, respectively.) On average, the majority of staff
      nurses and supervisors in individual agencies had associate degrees or diplomas.
      Nursing experience and medical-surgical nursing experience were of greater
      importance than having a B.S.N. or home health care experience for potential
      nursing applicants. Type, size, and age of agency and types of services provided
      had relatively little impact on staffing patterns. However, the director's degree
      was associated with the percentage of staff nurses and supervisors by educational
      degree. Competition had little impact on staffing patterns, although the extent
      of rural service area and Medicare involvement were related to educational
      backgrounds of nurses and hiring preferences.

PMID- 8309891
TI  - Maternal factors that influence inadequate prenatal care.
AB  - Fifty-seven pregnant women who received inadequate prenatal care identified the
      factors that influenced their decisions related to prenatal care. Data were
      collected in an institution that serves neighborhood clinics that offer free
      prenatal care and can be reached by public transportation. Women were interviewed
      either prenatally (n = 23) or postnatally (n = 34). The interview questions were
      drawn from the literature on the adequacy of prenatal care. The women identified
      22 personal reasons and structural barriers for receiving inadequate prenatal
      care. The five most frequently cited reasons were small children at home, no
      medical assistance card, didn't know reason, sadness or ambivalence about the
      pregnancy, and just moved to the area. Despite demographic risk and facing the
      similar barriers, some women manage to receive sufficient care and others do not.
      Presently, government and other policy-making groups often believe that public
      insurance, Medicaid, or socialized medicine is the answer to our high infant
      mortality rate. However, in some geographic areas where financial barriers are
      not factors and where services are available that meet pregnant women's needs,
      some women still do not enter care early and remain in care. Data that expand
      knowledge on why women receive inadequate prenatal care will be useful in
      developing community outreach programs, preparing public service announcements,
      and designing prenatal services.

PMID- 8309892
TI  - Loneliness, depression, and social support of patients with COPD and their
      spouses.
AB  - Thirty clients with chronic obstructive pulmonary disease (COPD) and their
      spouses were interviewed to examine differences in the relationships among
      loneliness, depression, and social support. Data were collected during structured
      in-home interviews using the UCLA loneliness scale, the Center for
      Epidemiological Studies depression scale, and the social support questionnaire.
      The clients and spouses did not differ significantly on measures of loneliness
      and depression, with mean scores for both groups higher than those in other
      comparable groups. Spouses, however, tended to be a little lonelier than clients,
      and clients tended to be a little more depressed than spouses. The two groups
      were also similar with respect to the number of people in their social networks
      but different as to network composition. Spouses were less satisfied with their
      networks than clients. Social support satisfaction was linked to loneliness and
      depression for clients but not for spouses. Results of the study suggest that
      community nurses working in home settings must be sensitive to clients' and
      spouses' psychologic reactions to COPD, which may be expressed in feelings of
      loneliness and depression.

PMID- 8309893
TI  - Lifestyle changes and coping patterns among caregivers of stroke survivors.
AB  - Although caregiving has been a major focus for research, little is known about
      the day-to-day changes in lifestyle faced by caregivers. Yet lifestyle, developed
      over time, manifests an individual's very identity. Using a multimethod approach,
      we assessed the perceptions of lifestyle changes and coping patterns of 20
      caregivers of first-time stroke survivors in the early poststroke period. An
      outcome-oriented matrix was employed for qualitative analysis, and findings were
      expanded by additional quantitative analysis. Three themes emerged: pervasiveness
      of lifestyle change, cohort differences in the perception of lifestyle change and
      coping patterns, and primary issues of time and confinement. Findings suggest
      that strains relative to caregiving may not be confined to direct caregiving
      activities, but may be related to established patterns of daily life.

PMID- 8309894
TI  - AIDS-related knowledge, fear, and behavioral change among nurses in Taiwan.
AB  - Current literature documents a phenomenon of fear that affects the willingness of
      health care professionals to care for persons with acquired immunodeficiency
      syndrome (AIDS). We attempted to identify differences between nurses who exhibit
      fearful attitudes toward AIDS and those who do not, based on knowledge and
      behavior. Taiwan, site of the study, is only beginning to identify the first of
      its citizens with AIDS. The subjects were a population of caregivers from a
      culture with little exposure, therefore, either through education or experience,
      to the disease and the issues it engenders. A cross-sectional, self-administered
      survey was conducted in 1990 of 1759 nurses in 12 institutions throughout Taiwan.
      Data on AIDS-related knowledge, fear, and behavior, as well as selected
      demographic data, were gathered. Analysis revealed significantly less fear of
      AIDS among nurses who reported three behavioral changes related to AIDS than
      among those who reported fewer changed behaviors (F = 4.43, df = 3; P < 0.004);
      those with higher levels of education (F = 3.54, df = 3; P < 0.014); and those
      who were single rather than married (t = 2.81; P < 0.005).

PMID- 8309895
TI  - Prenatal diagnosis of trisomy 9 mosaicism: two new cases.
AB  - We present two prenatal cases of trisomy 9 mosaicism, both of which presented
      intrauterine growth retardation (IUGR) and other abnormal ultrasound findings. In
      case A, mosaicism was found in amniotic fluid cell cultures, of which 65 per cent
      were trisomic cells, on average. In case B, trisomic cells were present in
      amniotic fluid cell cultures (12 per cent) but none were found in fetal cord
      blood. After autopsy, cytogenetic findings were confirmed in different tissue
      cultures. It is concluded that echographic indicators are a very useful tool for
      a correct prenatal diagnostic interpretation of trisomy 9. Suspected trisomy 9
      mosaicism always requires further investigation and fetal cord blood cytogenetic
      analysis may not be considered as providing an accurate diagnosis of fetal
      trisomy 9.

PMID- 8309896
TI  - Why confine chorionic villus biopsy to single pregnancies?

PMID- 8309897
TI  - Familial congenital diaphragmatic hernia: prenatal diagnosis, management, and
      outcome.
AB  - Congenital diaphragmatic hernia (CDH) is a developmental defect of as yet unknown
      aetiology which accounts for 8 per cent of all major congenital anomalies and is
      associated with up to 80 per cent mortality despite optimal postnatal treatment.
      The risk of recurrence of CDH for future sibs after one affected infant is about
      2 per cent. A multifactorial/threshold inheritance pattern with an observed high
      male:female sex ratio is currently favoured for the rare occurrence of familial
      CDH, although other modes of inheritance have also been described. We report
      three cases of familial CDH, two of whom were brother and sister sibs and the
      third was a first cousin, born within 18 months of each other. The diagnosis was
      by ultrasound and there were several factors predicting a poor outcome. The
      mortality in this group was 100 per cent. The prenatal diagnosis, treatment
      options, the unusual genetic aspects, outcome, and the pathology involved are
      discussed.

PMID- 8309898
TI  - Preaxial ray reduction defects as part of valproic acid embryofetopathy.
AB  - It is well known that prenatal exposure of valproic acid (VPA) may be associated
      with the occurrence of neural tube defects (Robert and Gibaud, 1982). Additional
      adverse effects related to VPA exposure include craniofacial abnormalities,
      skeletal defects, brain defects, cardiovascular defects, and urogenital defects
      (DiLiberti et al., 1984; Winter et al., 1987; Huot et al., 1987; Jager-Roman et
      al., 1986; Martinez-Frias, 1990). Recently, radial ray reduction has been
      reported as a severe type of skeletal defect associated with VPA exposure (Jager
      Roman et al., 1986; Huot et al., 1987; Verloes et al., 1990). We report two
      additional cases of this severe limb reduction defect as part of a broader
      pattern of altered morphogenesis in fetuses exposed to VPA and to confirm an
      association between such severe specific skeletal defects and VPA exposure. We
      briefly review teratologic studies in experimental animals which document the
      biologic plausibility of this association, and suggest that fetuses exposed to
      VPA undergo detailed prenatal ultrasonographic evaluation of the limbs.

PMID- 8309900
TI  - Cytogenetic diagnoses after chorionic villus sampling are less reliable in very
      high-or very-low-risk pregnancies.
AB  - An increasing number of cytogenetic prenatal diagnoses are performed on chorionic
      villus samplings. The accuracy of this method is influenced by chromosomal
      mosaicism, mostly confined to direct preparation methods. Especially those
      investigators who have experienced false-negative and false-positive findings
      propagate the combined use of direct and culture methods. Yet large collaborative
      studies have shown that in approximately two-thirds of diagnostic cases only one
      procedure is applied. Moreover, the accuracy of a cytogenetic investigation
      depends not only on the ontogenetic origin of the tissues investigated, but also
      on interacting factors such as the 'a priori risk' and the 'predictive value of a
      cytogenetic finding'. On this basis a differentiated prenatal diagnostic
      procedure is discussed, including either sole short-term culture (STC), combined
      STC and long-term culture (LTC), primary amniocentesis (AC), or primary
      percutaneous umbilical blood sampling (PUBS). The predictive value of the
      cytogenetic diagnosis from CVS varies significantly dependent on the a priori
      risk of a chromosome aberration and, in the case of an abnormal karyotype, on the
      specific chromosome involved. A non-mosaic and 'non-lethal' trisomy detected in
      STC is highly representative of the embryo/fetus, but there are exceptions of
      limited predictive value, e.g., trisomy 18. Guided by the strategy of an optional
      follow-up by LTC, AC, or PUBS in 1317 successive CV samplings, we are not aware
      of a false-negative diagnosis, but probably had one false-positive diagnosis:
      47,XXY after STC; 46,XY after LTC. When referring to the rate of fetuses with an
      unbalanced karyotype expected in the different indication groups, a relative
      increase of false-positive findings in the very-low-risk group (maternal age < or
      = 35 years of age) and of false-negative findings in the very-high-risk group
      (abnormal ultrasonographic findings) of pregnant women when only performing CVS
      becomes obvious. Because of this dilemma, AC or--especially in the latter group-
      PUBS might be primarily offered to these indication groups instead of CVS.

PMID- 8309899
TI  - Randomized trial comparing first-trimester transcervical chorionic villus
      sampling and second-trimester amniocentesis.
AB  - A total of 800 patients were randomized at the 9th to 11th week of pregnancy
      either for transcervical chorionic villus sampling (CVS) on the day of trial
      entry or for amniocentesis (AC) at the 16th week. The indication for fetal
      karyotyping was maternal age in 94 per cent of the cases; the mean maternal age
      was 39.2 years. An adequate sample was obtained in 98.3 per cent of the cases in
      the CVS group and in all cases in the AC group. Retesting was indicated in 3.3
      per cent of the CVS cases. An abnormal karyotype was found in 6.1 per cent of the
      CV samples and in 4.5 per cent of the amniotic fluid samples. There was one false
      positive chromosome result in both groups. Twelve (3.1 per cent) miscarriages
      occurred by the 22nd week of pregnancy in the CVS group in pregnancies intended
      to continue. No difference was seen between the groups for total fetal loss
      rates. The number of surviving infants in the CVS group was 92.2 per cent and in
      the AC group 91.7 per cent (rate difference 0.5 per cent (95 per cent confidence
      interval -3.3 to 4.3)). In our study, both the diagnostic accuracy and the risk
      of fetal loss were equal in the CVS and AC groups.

PMID- 8309901
TI  - Oral teratoma (epignathus) with intracranial extension: a report of two cases.
AB  - Epignathi are unusual congenital tumours presenting as oropharyngeal masses,
      often resulting in rapid asphyxia following birth. Occasionally, intracranial
      extension of the tumour is present, and two such cases are described. The
      presence of this complication, diagnosable by ultrasound examination, indicates
      that aggressive surgical treatment is inappropriate.

PMID- 8309902
TI  - Cleft palate: confirmation of prenatal diagnosis by colour Doppler ultrasound.
AB  - We present a case of a twin with trisomy 47,XX+i(9p) in whom the diagnosis of
      cleft palate was confirmed by colour Doppler imaging demonstrating abnormal fluid
      flow across the fetal pharyngeal bone defect. Application of this technique in
      cases predisposed for this congenital lesion may prove beneficial in the
      diagnosis of the more subtle types of isolated cleft palate.

PMID- 8309903
TI  - Rapid prenatal diagnosis of Patau's syndrome in a fetus with an abdominal wall
      defect by 72 hour culture of cells from amniotic fluid.
AB  - A woman in the 32nd week of pregnancy was referred for investigation because of
      fetal abnormalities, including an abdominal wall defect, detected by
      ultrasonography. In view of the increased risk of chromosome abnormality,
      amniocentesis was performed to enable informed decisions about the management of
      the pregnancy and delivery to be taken. Cells from the liquor were inoculated
      into standard lymphocyte culture medium and incubated for 72 h. Slides with a
      high mitotic index and good quality metaphases, comparable to those from a blood
      culture, were obtained after harvesting. Cytogenetic analysis showed the
      karyotype to be 46,XY, - 14,+t(13q14q), which is consistent with Patau's
      syndrome. This technique appears to be an option for rapid karyotyping in cases
      of abdominal wall defect, where a chromosomal abnormality is suspected.

PMID- 8309905
TI  - Doppler echocardiographic diagnosis of intrauterine closure of the ductus
      arteriosus.
AB  - A case of in utero closure of the ductus arteriosus was detected by Doppler
      echocardiography at 31 weeks of gestation. It presented as a non-hydropic
      distressed fetus with ultrasound detection of tricuspid regurgitation. Pulsed
      Doppler ultrasound showed markedly decreased blood flow through the tricuspid and
      pulmonary valves and absent blood flow at the ductus arteriosus. These, as well
      as the resultant increased right-to-left shunting across the foramen ovale, were
      reaffirmed by colour flow mapping.

PMID- 8309904
TI  - Prenatal diagnosis of a fetus with partial monosomy 7(q34-->qter) and partial
      trisomy 18(q21-->qter).
AB  - Ultrasound examination of a 31-year-old woman at 27 weeks' gestation revealed
      fetal growth retardation, a bilateral cleft lip and palate, and the absence of
      median cerebral structures. Chromosome analysis after cordocentesis showed an
      abnormal karyotype with a structural abnormality of the long arm of chromosome 7:
      46,XX,-7,+der(7),t(7;18) (q34;q21.3)mat. The pregnancy was terminated at week 29.
      The ultrasound findings were confirmed by post-mortem examination, which also
      revealed a semilobar holoprosencephaly.

PMID- 8309906
TI  - Prenatal diagnosis of anatomical connections in conjoined twins by use of
      contrast magnetic resonance imaging.
AB  - Omphalopagus conjoined twins were diagnosed by ultrasonography in a pregnant
      woman at 21 weeks' gestation. In order to clarify the anatomical connections,
      magnetic resonance imaging (MRI) was performed, having achieved fetal paralysis
      by intravascular injection of 100 mg of pancuronium into each twin. Prior to MRI,
      2 ml of a 0.0001 mmol/ml solution of gadolinium DTPA was also injected into the
      stomach of one twin. The contrast agent opacified the bowel loops of both twins,
      indicating bowel to bowel anastomosis. Following pregnancy termination, autopsy
      confirmed the prenatal diagnosis.

PMID- 8309907
TI  - [New quinolones, new indications].

PMID- 8309909
TI  - [Vancomycin in meningitis caused by penicillin G resistant Streptococcus
      pneumoniae].
AB  - We report two cases of penicillin G-resistant pneumococcal meningitis in adults,
      with clinical and bacteriological failure of amoxicillin and negative or
      incomplete response to third generation cephalosporins. Meningitis occurred in a
      man treated for myeloma and in an elderly woman under prolonged intermittent
      amoxicillin therapy for chronic otitis. Such situations are known as exposing to
      pneumococcal meningitis and to resistance of the strain involved to penicillin G.
      Both patients were cured by vancomycin in continuous infusion associated with
      rifampicin or fosfomycin. Contrary to third generation cephalosporins, which have
      higher minimal inhibitory concentrations, vancomycin and rifampicin are still
      fully active against penicillin G-resistant pneumococcal strains. Thus,
      vancomycin administered in continuous infusion and associated with rifampicin and
      fosfomycin deserves to be tried as first-line treatment of pneumococcal
      meningitis in patients at risk of resistance to penicillin G.

PMID- 8309908
TI  - [Continuous infusion of vancomycin in post-neurosurgical staphylococcal
      meningitis in adults].
AB  - Eight adult patients with post-surgery meningitis caused by methicillin-resistant
      staphylococci were treated with continuous intravenous infusion of vancomycin in
      mean doses of 50 mg/kg/day. This treatment, which lasted 3 to 6 weeks, was well
      tolerated by the kidneys and resulted in cure in all cases; its effect on the ear
      was not evaluated. Stable concentrations of 4 to 7 mg/l in cerebrospinal fluid
      were obtained after the 48th hour of treatment.

PMID- 8309910
TI  - [Tunnelized double femoral catheters. A technique for vascular access in
      hemodialysis].
AB  - OBJECTIVES: Temporary vascular access for haemodialysis is an everyday problem in
      a dialysis unit. We used the double catheter method developed for the internal
      jugular vein to catheterize the femoral vein in patients in which the jugular
      route could not be used. METHODS: A double catheter was inserted via
      percutaneous, bedside, punction into the femoral vein in 12 patients under local
      anaesthesia. The exit point was located near the middle of the thigh. RESULTS:
      Mean implantation time was 45 minutes. The inferior vena cava was the ideal site
      for the distal tip of the catheters. Mean duration of utilisation was 41 days
      (range 6-118) and allowed a mean of 28 haemodialysis sessions (range 4-49). Echo
      Doppler examinations after withdrawal did not reveal any thrombosis of the
      femoral, iliac or vena cava. CONCLUSIONS: When the jugular route is difficult or
      contraindicated, double femoral catheterism is a useful alternative vascular
      access for haemodialysis.

PMID- 8309911
TI  - [Non-parasitic cysts of the liver].
AB  - Solitary biliary cysts and polycystic liver disease are among the most frequent
      cystic lesions of the liver. Solitary biliary cysts have a prevalence of 1 to 2
      percent; they are almost always asymptomatic and do not require treatment.
      Ultrasonography shows a regular, round or oval, entirely liquid and trans-sonic
      image sufficient to make the diagnosis. Complications are exceptional. Polycystic
      liver disease is associated with polycystic kidney disease in 50 percent of the
      cases, and the prognosis depends on the degree of renal failure. In polycystic
      disease of the liver and kidney the hepatic cysts develop before the renal cysts.
      Complications (e.g. cyst infection) are rare and principally observed in patients
      with terminal renal failure. In patients with complicated polycystic liver
      disease various treatments, such as needle aspiration, alcohol sclerotherapy or
      surgery, must be considered.

PMID- 8309913
TI  - [Pulmonary lobectomy under video-endoscopy without thoracotomy].

PMID- 8309912
TI  - [Antiarrhythmic treatment after reduction of atrial fibrillation by external
      shock].
AB  - Among the drugs recommended to prevent recurrences of atrial fibrillation after
      external electric shock, antiarrhythmic agents of classes Ia (quinidine,
      disopyramide), Ic (cibenzoline, flecainide, propafenone) and III (sotalol) seem
      to have the same effectiveness in maintaining the sinus rhythm in about 50
      percent of the cases after 6 months and one year. Amiodarone, seldom used as
      first-line treatment, appears to be the most effective drug. The percentage of
      side-effects requiring discontinuation of treatment is the same for all drugs
      (about 10 percent). All these drugs have potential proarrhythmic effects. In case
      of recurrence electric shocks can be repeated in some special cases. The
      therapeutic strategy according to the clinical context (atrial fibrillation of
      vagal nerve or catecholergic origin, normal or altered left ventricular function)
      is discussed.

PMID- 8309914
TI  - [Radiotherapy in the management of atlantoaxial osteolytic bone metastases].

PMID- 8309915
TI  - [Munchhausen stridor: a psychiatric cause of acute dyspnea].

PMID- 8309916
TI  - [Spontaneous ruptures of the Achilles tendon after kidney transplantation: use of
      fluoroquinolones].

PMID- 8309917
TI  - [Breast cancer in the male].

PMID- 8309918
TI  - [Elevation of lipoprotein(a) in Horton disease].

PMID- 8309919
TI  - [Etiological diagnosis of syncope by the inclination test. How to determine
      positivity of the test?].

PMID- 8309920
TI  - [Recommendations for diagnostic bronchoalveolar lavage. German Society of
      Pneumology].
AB  - The working group "BAL" was established to develop guidelines and recommendations
      for the practical application of BAL. The indications and complications of the
      technique are shown, followed by recommendations for the bronchoscopic procedure
      to collect the samples, for the laboratory processing of the specimen and for the
      evaluation of the cytological preparations. Guidelines for the interpretation of
      BAL findings are given. Some normal values from the literature are listed.
      Disease characteristic changes are presented.

PMID- 8309921
TI  - [Psychogenic respiratory disorders].

PMID- 8309922
TI  - [Effect of a filter system on measurement data and bacterial contamination in
      lung function studies].
AB  - 80 measurements of the airway resistance of 20 patients did not yield any
      significant differences with or without using a bacterial filter (Pall PF 30) (p
      = 0.1213). Likewise, lung function tests conducted in 61 further patients did not
      reveal any relevant changes caused by introducing the filter, in respect of the
      lung function parameters VKin, FEV1, PEF, FEF25, FEF50, FEF75 and TLCO. In these
      studies the flow receptors were examined for contamination by bacteria. The
      introduction of the bacterial filter reduced the total count of identified germs
      from 108, 615 to 307, i.e. by 99.7 per cent, the greatest contamination being
      found in those parts that were close to the patient (57.6% with filter, 97.1%
      without filter). Germs of the resident flora of the mouth and pharynx were
      identified, and occasionally also potential infectious agents such as
      staphylococcus aureus and streptococcus pneumoniae. The use of a filter system
      results in a marked decrease in the exposition to germs in lung function tests,
      without exercising any adverse effect on the measurement data (cross
      contamination risk: 0.00078%). This is also achieved--albeit to a lesser extent-
      by changing those parts of the flow receptor that are close to the patient (cross
      contamination risk: 0.0841%). Hence, the use of a filter system appears
      particularly meaningful in patients with considerable immunodeficiency (advanced
      stages of HIV infection).

PMID- 8309923
TI  - [Detection of the IgE receptor CD23 in sarcoidosis].
AB  - In 30 sarcoidosis patients the soluble IgE receptor sCD23 was determined.
      Compared to healthy controls a marked increase of this molecule could be detected
      in serum (4.9 versus 0.9 ng/ml). In 19 patients who underwent bronchoscopy a
      strong expression of CD23 on alveolar macrophages could be demonstrated in
      immunochemistry compared to healthy controls (40.8 versus 12.6%). Determination
      of total IgE and anti-IgE antibodies did not allow discrimination between healthy
      controls and sarcoidosis patients. Our data suggest that alveolar macrophages are
      an important source for soluble CD23 in serum. CD23 expression might reflect
      functional activation of macrophages since our results do not appreciate a role
      for IgE-related reactions in sarcoidosis.

PMID- 8309924
TI  - [Physical therapy with VRP1 in chronic obstructive respiratory tract diseases-
      results of a multicenter comparative study].
AB  - In a multicenter group comparative study with 51 patients suffering from chronic
      obstructive lung diseases, efficacy and tolerance of physiotherapy with the VRP1
      Desitin was investigated. In comparison with the control group (concomitant
      respiratory physiotherapy) a statistically significant increase in the lung
      function parameter VC, FEV1 and PEF was demonstrated in the VRP1 Desitin-group
      after 2 weeks of investigation. Auscultatory findings as well as the clinical
      symptoms cough, sputum and dyspnea were clearly improved. The patients observed
      an improvement in their condition and capability.

PMID- 8309925
TI  - [Double infection of the lung with Pneumocystis carinii and Cryptococcus
      neoformans in an AIDS patient].
AB  - A 25-year old HIV-1-positive hemophiliac was admitted with fever, cough,
      exertional dyspnea and pleuritic chest pain. Chest x-ray showed diffuse bilateral
      infiltrates with a left sided nodular consolidation. Pneumocystis-carinii
      pneumonia was suspected and diagnosed by broncho-alveolar lavage. With therapy
      the diffuse infiltrates improved, but the nodule and the symptoms failed to
      resolve. A fine-needle aspiration of the nodule revealed concurrent
      cryptococcosis. Treatment with fluconazole resulted in complete resolution of
      symptoms. Details of the case are presented and clinical implications are
      discussed.

PMID- 8309926
TI  - A new approach to the design of stable proteins.
AB  - We propose a simple algorithm to design a sequence which fits a given protein
      structure with a given energy. The algorithm is a modification of the Metropolis
      Monte Carlo scheme in sequence space with an evolutionary temperature which sets
      the energy scale. There is a one to one correspondence between this optimization
      scheme and the Ising model of ferromagnetism. This analogy implies that the
      design algorithm does not encounter multiple-minima problems and is very fast.
      The algorithm is tested by 'predicting' the primary structures of four proteins.
      In each case the calculated primary structures had statistically significant
      homology with the natural structures.

PMID- 8309927
TI  - Regularities in interaction patterns of globular proteins.
AB  - The description of protein structure in the language of side chain contact maps
      is shown to offer many advantages over more traditional approaches. Because it
      focuses on side chain interactions, it aids in the discovery, study and
      classification of similarities between interactions defining particular protein
      folds and offers new insights into the rules of protein structure. For example,
      there is a small number of characteristic patterns of interactions between
      protein supersecondary structural fragments, which can be seen in various non
      related proteins. Furthermore, the overlap of the side chain contact maps of two
      proteins provides a new measure of protein structure similarity. As shown in
      several examples, alignments based on contact map overlaps are a powerful
      alternative to other structure-based alignments.

PMID- 8309929
TI  - Improved alignment of weakly homologous protein sequences using structural
      information.
AB  - Protein sequence alignments can be improved when at least one of the proteins to
      be aligned has a known 3-D structure. In this work, geometrical constraints
      extracted from the target fold are evaluated in independent units that deal with
      complementary structural features. This information is used to set up mutation
      tables specific to the locally observed structural environments. The resulting
      partial evaluations are then combined linearly into a global function which is
      optimized by dynamic programming. Eventually, a score based on tertiary
      interactions can be used as a selection criterion to discriminate among a set of
      suboptimal alignments. The relevance of the scores given by each unit is tested
      on a representative set of protein families. Finally, a method for combining the
      different scores is described and its efficiency is evaluated on a few pairs of
      weakly homologous proteins.

PMID- 8309928
TI  - Development of pseudoenergy potentials for assessing protein 3-D-1-D
      compatibility and detecting weak homologies.
AB  - Recent approaches to the 3-D-1-D compatibility problem have tried to predict
      protein 3-D structure from sequence. One of the critical factors in this issue is
      the evaluation of fitness between a given 3-D structure and any sequence mounted
      on it. We have developed an evaluation function composed of four terms, side
      chain packing, hydration, hydrogen bonding and local conformation potentials,
      which were empirically derived from 101 proteins of known structure. The
      efficiency of the evaluation function was tested in two ways. In the first test,
      the sequence of protein A is mounted (without gaps) on the structure of protein B
      which is greater in size than A. For 81 proteins examined, the native structure
      was always detected. In the second test, a standard sequence homology search is
      performed against the entire database, followed by an assessment of the alignment
      with its proposed structure, using the empirical evaluation function. When this
      test was applied to the 101 proteins, our evaluation function successfully
      discriminated truly homologous sequence pairs from non-homologous proteins even
      when the sequence similarities were very weak. This approach was found to have
      clear advantages over conventional sequence search methods.

PMID- 8309930
TI  - Secondary structure prediction of all-helical proteins in two states.
AB  - Can secondary structure prediction be improved by prediction rules that focus on
      a particular structural class of proteins? To help answer this question, we have
      assessed the accuracy of prediction for all-helical proteins, using two
      conceptually different methods and two levels of description. An overall two
      state single-residue accuracy of approximately 80% can be obtained by a neural
      network, no matter whether it is trained on two states (helix and non-helix) or
      first trained on three states (helix, strand and loop) and then evaluated on two
      states. For four test proteins, this is similar to the accuracy obtained with
      inductive logic programming. We conclude that on the level of secondary
      structure, there is no practical advantage in training on two states, especially
      given the added margin of error in identifying the structural class of a protein.
      In the further development of these methods, it is increasingly important to
      focus on aspects of secondary structure that aid in the construction of a correct
      3-D model, such as the correct placement of segments.

PMID- 8309931
TI  - Improvement of turn structure prediction by molecular dynamics: a case study of
      alpha 1-purothionin.
AB  - Because of the problems in predicting a correct conformation for loop regions in
      homology-based prediction, disagreements are often found between the predicted
      models and the refined X-ray structures of the same protein in loop regions. Such
      a situation has been encountered for alpha 1-purothionin (alpha 1-PT). Hence,
      attempts have been made to improve the predicted model of alpha 1-PT by limited
      molecular dynamics using both AMBER and XPLOR. With molecular dynamics, the
      previously predicted incorrect turn region reverts to the correct conformation as
      seen in the X-ray refined structure. In contrast to the model which is not
      subjected to molecular dynamics, the improved model refines with the X-ray data
      of alpha 1-PT in fewer cycles, without any manual rebuilding and with comparable
      or better refinement statistics. Also, the improved model serves as a better
      starting model in the determination of the structure with the molecular
      replacement methods.

PMID- 8309932
TI  - Quantification of secondary structure prediction improvement using multiple
      alignments.
AB  - The use of multiple sequence alignments for secondary structure predictions is
      analysed. Seven different protein families, containing only sequences of known
      structure, were considered to provide a range of alignment and prediction
      conditions. Using alignments obtained by spatial superposition of main chain
      atoms in known tertiary protein structures allowed a mean of 8% in secondary
      structure prediction accuracy, when compared to those obtained from the
      individual sequences. Substitution of these alignments by those determined
      directly from an automated sequence alignment algorithm showed variations in the
      prediction accuracy which correlated with the quality of the multiple alignments
      and distance of the primary sequence. Secondary structure predictions can be
      reliably improved using alignments from an automatic alignment procedure with a
      mean increase of 6.8%, giving an overall prediction accuracy of 68.5%, if there
      is a minimum of 25% sequence identity between all sequences in a family.

PMID- 8309933
TI  - Theoretical studies of Rhizomucor miehei lipase activation.
AB  - Computational methods have been used to study the extensive conformational change
      of Rhizomucor miehei lipase upon activation. The present study considers the
      possible activation route, the energies involved and molecular interactions
      during the conformational change of the lipase in a hydrophobic environment. The
      conformational change was studied by conventional molecular dynamics methods and
      with a combined molecular dynamics and mechanics protocol, in which the
      conformational change was simulated by restraining C alpha pseudotorsional angles
      in small steps between the two crystallographically observed positions of the
      lid. In the closed conformer of the enzyme the active site is completely buried
      under a short helical loop, 'the lid'. The activation of the lipase consists of a
      movement of the lid, which results in an open conformer with an exposed active
      site. From the results of the simulations in the present work we suggest that the
      lipase in a hydrophobic environment is stabilized in the open form by
      electrostatic interactions.

PMID- 8309934
TI  - Model structures and action of interleukin 1 and its antagonist.
AB  - A comparison has been made between the homology and hydrophobicity profiles of
      six interleukin amino acid sequences and that of the human interleukin 1 beta (IL
      1 beta) for which a crystal structure exists. The resulting sequence alignment
      was used to build model structures for the sequences for three IL-1 alpha, two IL
      1 beta and an interleukin receptor antagonist. Analysis of these structures
      demonstrates that the interleukin molecule has a strong electric dipole which is
      generated by the topological position of the amino acids in the sequence.
      Electrostatic surface calculations implicate a particular residues (Lys145) as
      being fundamental to interleukin activity and this supports site-directed
      mutation evidence that this residue is required for activity.

PMID- 8309935
TI  - Modelling multiple disulphide loop containing polypeptides by random conformation
      generation. The test cases of alpha-conotoxin GI and endothelin I.
AB  - A general procedure for arriving at 3-D models of disulphide-rich polypeptide
      systems based on the covalent cross-link constraints has been developed. The
      procedure, which has been coded as a computer program, RANMOD, assigns a large
      number of random, permitted backbone conformations to the polypeptide and
      identifies stereochemically acceptable structures as plausible models based on
      strainless disulphide bridge modelling. Disulphide bond modelling is performed
      using the procedure MODIP developed earlier, in connection with the choice of
      suitable sites where disulphide bonds could be engineered in proteins
      (Sowdhamini, R., Srinivasan, N., Shoichet, B., Santi, D.V., Ramakrishnan, C. and
      Balaram, P. (1989) Protein Engng, 3, 95-103). The method RANMOD has been tested
      on small disulphide loops and the structures compared against preferred backbone
      conformations derived from an analysis of putative disulphide subdatabase and
      model calculations. RANMOD has been applied to disulphide-rich peptides and found
      to give rise to several stereochemically acceptable structures. The results
      obtained on the modelling of two test cases, alpha-conotoxin GI and endothelin I,
      are presented. Available NMR data suggest that such small systems exhibit
      conformational heterogeneity in solution. Hence, this approach for obtaining
      several distinct models is particularly attractive for the study of
      conformational excursions.

PMID- 8309936
TI  - Analysis of RNA phage fr coat protein assembly by insertion, deletion and
      substitution mutagenesis.
AB  - A structure-function analysis of the icosahedral RNA bacteriophage fr coat
      protein (CP) assembly was undertaken using linker-insertion, deletion and
      substitution mutagenesis. Mutations were specifically introduced into either pre
      existing or artificially created restriction enzyme sites within fr CP gene
      expressed in Escherichia coli from a recombinant plasmid. This directs synthesis
      of wild type protein that undergoes self-assembly and forms capsid-like particles
      indistinguishable morphologically and immunologically from native phage
      particles. A series of fr CP variants containing sequence alterations in the
      regions which are (i) exposed on the external surface of capsid or (ii) located
      on the contacting areas between CP subunits were obtained and their assembly
      properties investigated. The majority of mutants demonstrated reduction of
      assembly ability and formed either CP dimers (mutations at residues 2, 10, 63 or
      129) or both dimer and capsid structures (residue 2 or 69). The exceptions were
      variants demonstrating normal assembly and containing insertions at residues 2,
      50 or 129 of the fr CP. A third type of assembled structure was formed by a
      variant with a single amino acid substitution I104T. The alpha A-helix region
      (residues 97-111) is particularly sensitive to mutation and any alteration in
      this region decreases accumulation of mutant protein in E. coli. The relative
      contributions of particular fr CP domains in maintenance of capsid structural
      integrity as well as the possible capsid assembly mechanism are discussed.

PMID- 8309938
TI  - Identification by site-directed mutagenesis of amino acids in the B2 subsite of
      bovine pancreatic ribonuclease A.
AB  - In addition to hydrolysing RNA, bovine pancreatic ribonuclease splits esters of
      pyrimidine nucleoside 3'-phosphates, including dinucleotides. For a series of
      3':5'-linked dinucleotides of general structure CpN, where N is a 5' linked
      nucleoside, kcat for the release of N varies enormously with the precise
      structure of N. Structural studies have been interpreted to indicate that the
      group N interacts with a subsite, B2, on the enzyme that comprises Gln69, Asn71
      and Glu111. We report studies by site-directed mutagenesis that indicate that
      Gln69 is not involved in productive interactions with any of the dinucleotide
      substrates and that Asn71 is an important component of subsite B2 for all
      dinucleotide substrates tested. Glu111 appears to be functionally involved in
      catalysis for dinucleotide substrates solely when N is guanosine.

PMID- 8309937
TI  - Replacing the (beta alpha)-unit 8 of E.coli TIM with its chicken homologue leads
      to a stable and active hybrid enzyme.
AB  - In order to investigate how structural modifications interfere with protein
      stability, we modified a (beta alpha)-unit in E.coli triosephosphate isomerase
      (TIM), a typical (beta alpha)-barrel protein, assuming that the pseudosymmetrical
      beta-barrel can be divided into eight successive loop/beta-strand/loop/alpha
      helix motifs. We replaced the eighth (beta alpha)-unit of E.coli TIM with the
      corresponding chicken (beta alpha)-unit. The substitution, involving the
      replacement of 10 of the 23 residues of this (beta alpha)-unit, was evaluated
      first by modelling, then experimentally. Modelling by homology suggests how the
      amino acid replacements might be accommodated in the hybrid E.coli/chicken TIM
      (ETIM8CHI). Both natural and hybrid recombinant TIMs, overproduced in E.coli,
      were purified to homogeneity and characterized as to their stability and
      kinetics. Our kinetic studies show that the modification performed here leads to
      an active enzyme. The stability studies indicate that the stability of ETIM8CHI
      is comparable to that of the wild type TIM.

PMID- 8309939
TI  - Zinc ions bound to chimeric His4/lactate dehydrogenase facilitate decarboxylation
      of oxaloacetate.
AB  - A chemically synthesized DNA linker coding for a peptide fragment that contains
      four histidines was fused in-frame to the 5'-end of the Bacillus
      stearothermophilus lactate dehydrogenase gene. The gene product, His4/lactate
      dehydrogenase, could be purified to homogeneity using either immobilized metal
      (Zn2+)-affinity chromatography or affinity chromatography on oxamate agarose. The
      stability against heat and urea for the modified enzymes was decreased as
      compared to the native lactate dehydrogenase but could be increased if zinc ions
      were present during the denaturation. In the presence of zinc ions the
      His4/lactate dehydrogenase could catalyse the sequential reaction from
      oxaloacetate to L-lactate, hence operating as a semi-synthetic bifunctional
      enzyme. A small increase in the apparent second-order rate constant (kcat/Km) of
      the coupled reaction was observed as compared to a corresponding system with
      native lactate dehydrogenase.

PMID- 8309940
TI  - 6-Phospho-beta-galactosidases of gram-positive and 6-phospho-beta-glucosidase B
      of gram-negative bacteria: comparison of structure and function by kinetic and
      immunological methods and mutagenesis of the lacG gene of Staphylococcus aureus.
AB  - The 6-phospho-beta-galactosidase of Staphylococcus aureus, Lactococcus lactis and
      Lactobacillus casei and 6-phospho-beta-glucosidase B of Escherichia coli build a
      subfamily inside a greater enzyme family, named the glycosal hydrolase family 1,
      which, in addition, contains nine beta-glycosidases of different origins. Kinetic
      and immunological evidence is provided in this report which strengthens the
      relationship of the four 6-phospho-beta-glycosidases. It is shown that the 6
      phospho-beta-galactosidases and 6-phospho-beta-glucosidase B are able to split
      aromatic beta-galactoside phosphates and beta-glucoside phosphates. The turnover
      numbers of hydrolysis of substrates with different epimerization at C-4 of the
      glycon vary up to 15-fold only. Two polyclonal antisera, one derived against the
      native 6-phospho-beta-galactosidase from S. aureus and the other derived against
      the 6-phospho-beta-glucosidase B, cross-reacted with both enzymes. Peptides of
      the proteins were separated by reverse phase HPLC. The cross-reacting peptides
      were sequenced and shown to be localized at almost the same position in the
      aligned primary structures of both enzymes. An insertion of nine amino acids near
      these antigenic domains is unique for the 6-phospho-beta-glycosidases and missing
      within the sequences of the beta-glycoside-specific members of the family. The
      lacG gene of a 6-phospho-beta-galactosidase negative S. aureus mutant was cloned
      into E. coli and sequenced. In the totally inactive mutant protein only the
      glycine at position 332 was changed to an arginine. This amino acid is part of
      the sequence insertion near the antigenic domain reacting with both
      antisera.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309941
TI  - Identification of two amino acids contributing the high enzyme activity in the
      alkaline pH range of an alkaline endoglucanase from a Bacillus sp.
AB  - An alkaline cellulase (beta-1,4-endoglucanase; NK1) from an alkalophilic Bacillus
      sp. shows great similarity in amino acid sequence to a neutral cellulase (BSC)
      from Bacillus subtilis, despite a considerable difference in their pH activity
      profiles. Multiple amino acid exchanges by site-directed mutagenesis, using BSC
      as the reference, were performed on the residues in region 5 of NK1, which was
      previously shown to be responsible for the high enzyme activity of this alkaline
      cellulase in a broad alkaline pH range. Two amino acid residues, Ser287 and
      Ala296, were identified as being responsible for the activity in the alkaline
      range. The double mutation, Ser287 to Asn and Ala296 to Ser, of NK1 made its pH
      activity profile almost the same as that of BSC. On the other hand, the pH
      activity profile in the acidic range was not significantly affected by various
      amino acid replacements including these two positions in region 5. This
      observation, together with the information available on other endoglucanases,
      suggests that the above two amino acid substitutions caused a profound effect
      through rearrangement of the hydrogen bond network forming the substrate-binding
      site or the catalytic site.

PMID- 8309942
TI  - Engineering of the substrate-binding region of the subtilisin-like, cell-envelope
      proteinase of Lactococcus lactis.
AB  - The substrate-binding region of the cell-envelope proteinase of Lactococcus
      lactis strain SK11 was modelled, based on sequence homology of the catalytic
      domain with the serine proteinases subtilisin and thermitase. Substitutions,
      deletions and insertions were introduced, by site-directed and cassette
      mutagenesis of the prtP gene encoding this enzyme, based on sequence comparison
      both with subtilisin and with the homologous L.lactis strain Wg2 proteinase,
      which has different proteolytic properties. The engineered enzymes were
      investigated for thermal stability, proteolytic activity and cleavage specificity
      towards small chromogenic peptide substrates and the peptide alpha s1-casein(1
      23). Mutations in the subtilisin-like substrate-binding region showed that Ser433
      is the active site residue, and that residues 138 and 166 at either side of the
      binding cleft play an important role in substrate specificity, particularly when
      these residues and the substrate are oppositely charged. The K748T mutation in a
      different domain also affected specificity and stability, suggesting that this
      residue is in close proximity to the subtilisin-like domain and may form part of
      the substrate-binding site. Several mutant SK11 proteinases have novel properties
      not previously encountered in natural variants. Replacements of residues 137
      139AKT along one side of the binding cleft produced the 137-139GPP mutant
      proteinase with reduced activity and narrowed specificity, and the 137-139GLA
      mutant with increased activity and broader specificity. Furthermore, the 137
      139GDT mutant had a specificity towards alpha s1-casein(1-23) closely resembling
      that of L.lactis Wg2 proteinase. Mutants with an additional negative charge in
      the binding region were more stable towards autoproteolysis.

PMID- 8309943
TI  - Cassette mutagenesis of Aspergillus awamori glucoamylase near its general acid
      residue to probe its catalytic and pH properties.
AB  - Nine single amino acid mutations in the active site of Aspergillus awamori
      glucoamylase were made by cassette mutagenesis to alter the pH dependence of the
      enzyme and to determine possible functions of the mutated residues. The Glu179-
      >Asp mutation expressed in yeast led to a very large decrease in kcat but to no
      change in Km, verifying this residue's catalytic function. Asp176-->Glu and
      Glu180-->Asp mutations affected Km more than kcat, implying that Asp176 and
      Glu180 are involved in substrate binding or structural integrity. The Leu177-
      >Asp mutation decreased kcat only moderately, probably by changing the position
      of the general acid catalytic group, and did not affect Km. The Trp178-->Asp
      mutation greatly decreased kcat while increasing Km, showing the importance of
      Trp178 in the active site. Val181-->Asp and Asn182-->Asp mutations changed
      kinetic values little, suggesting that Val181 and Asn182 are of minor catalytic
      and structural importance. Finally, insertions of Asp or Gly between residues 176
      and 177 resulted in almost complete loss of activity, probably caused by
      destruction of the active site structure. No large changes in pH dependence
      occurred in those mutations where kinetic values could be determined, in spite of
      the increase in most cases of the total negative charge. Increases in activation
      energy of maltoheptaose hydrolysis in most of the mutant glucoamylases suggested
      cleavage of individual hydrogen bonds in enzyme-substrate complexes.

PMID- 8309944
TI  - Properties conferred on Clostridium thermocellum endoglucanase CelC by grafting
      the duplicated segment of endoglucanase CelD.
AB  - The DNA sequence encoding the duplicated 22 amino acid segment of Clostridium
      thermocellum endoglucanase CelD was fused to the 3'-terminus of the celC gene
      encoding C.thermocellum endoglucanase CelC. The presence of the duplicated
      segment endowed CelC with the capacity to form cytoplasmic inclusion bodies
      containing active enzyme when the hybrid gene was expressed in Escherichia coli.
      Inclusion body formation prevented proteolytic cleavage of the duplicated
      segment. The intact hybrid protein CelC-Cel'D was purified from inclusion bodies
      and characterized. In contrast to CelC, CelC-Cel'D was able to bind to CipA, a
      protein acting as a scaffolding component of the C.thermocellum cellulase complex
      (cellulosome). However, the catalytic properties of CelC-Cel'D were similar to
      those of CelC. These results suggest that foreign proteins tagged with the
      duplicated segment could be incorporated into the cellulosome in order to modify
      the enzymatic properties of the complex. The formation of inclusion bodies by
      proteins carrying the duplicated segment may also prove a convenient means of
      purifying cloned gene products that are sensitive to proteolytic degradation.

PMID- 8309945
TI  - The expression of bovine microsomal cytochrome b5 in Escherichia coli and a study
      of the solution structure and stability of variant proteins.
AB  - The DNA sequence of bovine microsomal cytochrome b5 has been amplified from a
      liver cDNA library using a polymerase chain reaction. The amplified cDNA when
      cloned into plasmids that support the high-level production of cytochrome b5 in
      E.coli leads to protein overexpression and results in cell colonies bearing a
      strong red colouration. Using cassette mutagenesis, truncated versions of the
      cytochrome b5 cDNA have been made that encode the first 90 amino acid residues
      (Ala1-Lys90), the first 104 amino acids (Ala1-Ser104) and the complete protein
      (Ala1-Asn133). The location of the overexpressed cytochrome b5 within prokaryotic
      cells is dependent on the overall length of the protein. Expression of the Ala
      Lys90 and Ala1-Ser104 variants leads to a location in the cytoplasmic phase of
      the bacteria whereas the whole protein, Ala1-Asn133, is found within the
      bacterial membrane fraction. The last 30 residues of cytochrome b5 therefore
      contain all of the necessary information to insert the protein into E.coli
      membranes. The solubility of the Ala1-Ser104 variant permits the solution
      structure and stability of this protein to be measured using 1- and 2-D 1H-NMR
      methods and electronic spectroscopy. 1-D NMR studies show that the chemical
      shifts of the haem and haem ligand resonances of the Ala1-Ser104 variant exhibit
      only very slight perturbations to their magnetic microenvironments when compared
      with the tryptic fragment of ferricytochrome b5. These results indicate an
      arrangement of residues in the haem pocket that is very similar in both the Ala1
      Ser104 variant and the tryptic fragment and by 2-D NMR it is shown that this
      similarity extends to the conformations of the polypeptide backbone and side
      chains. Electronic spectroscopy of this variant shows absorbance maxima for the
      Soret peaks at 423 nm (reduced) and 413 nm (oxidized). From absorbance spectra
      the relative thermal stabilities of the Ala1-Ser104 variant and the tryptic
      fragment were measured. In the oxidized state the Ala1-Ser104 variant denatures
      in a single cooperative transition with a midpoint temperature (Tm) of 73 degrees
      C that is significantly higher than that of 'tryptic' ferricytochrome b5. The
      reduced form of the protein shows increased transition temperatures (Tm
      approximately 78 degrees C) reflected in the values of delta Hm, delta Sm and
      delta(delta G) of 420 kJ/mol, 1096 J/mol/K and 12.38 kJ/mol respectively,
      estimated for this variant. The increased stability of the Ala1-Ser104 variant
      and other recombinant forms of cytochrome b5 is correlated with the presence of
      additional residues at the N- and C-termini.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8309946
TI  - Humanization of a mouse anti-human IgE antibody: a potential therapeutic for IgE
      mediated allergies.
AB  - Mouse mAb TES-C21(C21) recognizes an epitope on human IgE and, therefore, has
      potential as a therapeutic agent in patients with IgE-mediated allergies such as
      hay fever, food and drug allergies and extrinsic asthma. The clinical usefulness
      of mouse antibodies is limited, however, due to their immunogenicity in humans.
      Mouse C21 antibody was humanized by complementarity determining region (CDR)
      grafting with the aim of developing an effective and safe therapeutic for the
      treatment of IgE-mediated allergies. The CDR-grafted, or reshaped human, C21
      variable regions were carefully designed using a specially constructed molecular
      model of the mouse C21 variable regions. A key step in the design of reshaped
      human variable regions is the selection of the human framework regions (FRs) to
      serve as the backbones of the reshaped human variable regions. Two approaches to
      the selection of human FRs were tested: (i) selection from human consensus
      sequences and (ii) selection from individual human antibodies. The reshaped human
      and mouse C21 antibodies were tested and compared using a biosensor to measure
      the kinetics of binding to human IgE. Surprisingly, a few of the reshaped human
      C21 antibodies exhibited patterns of binding and affinities that were essentially
      identical to those of mouse C21 antibody.

PMID- 8309947
TI  - Cloning, sequencing and expression of the Fab fragment of a monoclonal antibody
      to the herbicide atrazine.
AB  - The Fab region of an IgG2b antibody (AM7B2.1) reactive to the herbicide atrazine
      was cloned into a plasmid vector using the polymerase chain reaction and two sets
      of degenerate oligonucleotide primers designed to mimic the amino acid variation
      at the N-termini of kappa L-chains and gamma H-chains. These primers also provide
      a secretion signal fused precisely to the antibody gene sequence for secretion of
      the mature antibody. A further set of universal oligonucleotide primers was
      developed for the direct sequencing of the VH and CH1 regions of gamma H-chains
      and the VL and CL regions of kappa L-chains without subcloning and were used to
      determine the sequence of this antibody. The kappa L-chain was found to not
      possess a conserved Cys residue at position 23 and the implications of this
      observation are discussed. The cloned genes were expressed in Escherichia coli
      using a commercially available T7 RNA polymerase-based plasmid. The clones were
      also expressed in a T7 RNA polymerase-based system containing an attenuated
      version of the T7 RNA polymerase promoter, plus a lac promoter placed in an
      antisense orientation, to enhance plasmid stability. The expressed products were
      confirmed as atrazine reactive by binding to an atrazine derivative conjugated
      with alkaline phosphatase.

PMID- 8309948
TI  - An improved linker for single-chain Fv with reduced aggregation and enhanced
      proteolytic stability.
AB  - The effects of linker length on binding affinity and degree of aggregation have
      been examined in the antifluorescein 4-4-20 and anticarcinoma CC49 single-chain
      Fvs. Longer linkers in the antifluorescein sFvs have higher affinities for
      fluorescein and aggregate less. A proteolytically susceptible site between Lys8
      and Ser9, in the previously reported 212 linker has been identified. A new linker
      sequence, 218 (GSTSGSGKPGSGEGSTKG) was designed in which a proline was placed at
      the C-terminal side of the proteolytic clip site in the 212 linker. The CC49 sFv
      containing the 218 linker showed reduced aggregation and was found to be more
      stable to proteolysis in vitro, when compared to the CC49/212 sFv. The CC49 sFv
      with the longer 218 linker had higher affinity than CC49/212 sFv. An aggregated
      CC49/212 sFv sample had higher affinity than CC49/218 sFv. The CC49/218 and
      CC49/212 sFvs had similar blood clearances in mice, while the aggregated CC49/212
      sFv remained in circulation significantly longer. In mice bearing LS-174T human
      colon carcinoma xenografts, the CC49/218 sFv showed higher tumor uptake than the
      CC49/212 sFv and lower tumor uptake than the aggregated CC49/212 sFv. The higher
      tumor uptake of the CC49/218 is most likely a result of its higher resistance to
      proteolysis. The higher affinity and higher tumor uptake of the aggregated
      CC49/212 sFv are most likely due to the repetitive nature of the TAG-72 antigen
      and the higher avidity of multivalent aggregates. When the sFvs were radiolabeled
      with a lutetium-chelate the CC49/218 sFv showed a lower accumulation in the liver
      and spleen compared to the aggregated CC49/212 sFv.

PMID- 8309949
TI  - Inhibitors of sterol biosynthesis and their applications.

PMID- 8309950
TI  - Prostanoid receptors and their biological actions.

PMID- 8309951
TI  - Bradykinin suppresses alcohol intake and plays a role in the suppression produced
      by an ACE inhibitor.
AB  - The possible role of the endogenous kinins in the control of alcohol intake was
      assessed in two experiments. In Experiment 1, naive rats, maintained on ad lib
      food and water, were given daily 40-min access to a 6% (w/v) alcohol solution and
      water. Daily intraperitoneal (IP) injections of captopril (20 mg/kg)
      significantly reduced alcohol intake, while pretreatment with subcutaneous (SC)
      injections of the bradykinin antagonist [D-Phe7]-bradykinin (100-300
      micrograms/kg) attenuated the suppressive effect of captopril on alcohol intake.
      The saline vehicle or the bradykinin antagonist alone did not alter alcohol
      intake. In Experiment 2, bradykinin was administered daily at 100, 200, and 400
      micrograms/kg doses SC either alone or in combination with captopril 10 mg/kg IP.
      Neither bradykinin nor captopril by themselves changed alcohol or water intake.
      Bradykinin combined with captopril stimulated water intake and reduced alcohol
      intake by up to 70%. This effect was not due to drug-induced changes in the
      pharmacokinetics of alcohol. The angiotensin II receptor antagonist [Sar1,Thr8]
      angiotensin II at 250 and 500 micrograms/kg SC attenuated the stimulation of
      water intake but not the reduction in alcohol intake. It is suggested that by
      inhibiting kininase II, ACE inhibitors extend the duration of action of
      bradykinin and thereby unmask a potent inhibition of alcohol intake mediated by
      kinins--an effect that is dissociable from the accompanying stimulation of water
      intake. Taken together, these results point to an involvement of the kinin system
      in the regulation of alcohol intake and in particular to a role of bradykinin in
      the suppressive effect of ACE inhibitors on alcohol intake.

PMID- 8309952
TI  - Selective D1 and D2 dopamine receptor antagonists produce differential effects on
      reaction time in the rat.
AB  - The purpose of this investigation was to determine whether selectively blocking
      D1 and D2 dopamine receptors produces a differential effect on the
      characteristics (speed and success) of the reaction time response in rats.
      Animals were shaped to release a lever in response to an auditory/visual stimulus
      to avoid mild foot shock. The selective D1 antagonist SCH 23390 (0, 70, and 100
      micrograms/kg, IP) and the selective D2 antagonists spiperone (0, 1, and 10
      micrograms/kg, IP) and haloperidol (0, 10, and 100 micrograms/kg, IP) were
      studied for their effects on successful avoidance and response latency. SCH 23390
      impaired successful avoidance and increased response latencies in a dose
      dependent manner. Spiperone and haloperidol also produced dose-related decreases
      in successful avoidance. In contrast to the dose-related increase in response
      latencies produced by SCH 23990, 1 microgram/kg spiperone and 10 micrograms/kg
      haloperidol significantly decreased the latencies of successful responses.
      Spiperone (10 micrograms/kg) had little effect on response latencies, while 100
      micrograms/kg haloperidol increased them. The results of these experiments
      demonstrate that reaction time is differentially affected by selective dopamine
      receptor blockade and that the speed and success of reaction time responses can
      be independently modulated by D1 vs. D2 receptor activity.

PMID- 8309953
TI  - Apomorphine and amphetamine produce differential effects on the speed and success
      of reaction time responding in the rat.
AB  - Apomorphine, a nonselective, direct-acting dopamine agonist, and amphetamine, a
      nonselective indirect-acting dopamine agonist, were compared for their effects on
      the reaction time response in rats. Animals were shaped to release a lever in
      response to an auditory/visual stimulus to avoid mild foot shock. The
      characteristics of the reaction time response of primary interest were percent
      successful avoidance and response latency. Apomorphine (0, 1, and 5 mg/kg, IP)
      significantly decreased successful avoidance, but had no effect on response
      latencies. Thus, the decrease in successful avoidance was not a direct result of
      longer latencies. Amphetamine (0, 0.5, and 1 mg/kg, IP) produced a different
      pattern of effects on the reaction time response. Successful avoidance was not
      affected by amphetamine treatment. However, response latencies were dose
      dependently decreased in response to amphetamine. These results demonstrate that
      dopamine receptor stimulation by different dopamine agonists produces a different
      pattern of effects on the characteristics of the reaction time response. In
      addition, these results demonstrate that successful avoidance can be modulated
      independently of response latencies.

PMID- 8309954
TI  - Sex differences in the antinociceptive effects of the enkephalinase inhibitor,
      SCH 34826.
AB  - The effects of endogenous opioid peptides are limited by proteolytic enzymes such
      as endopeptidase 24.11 ("enkephalinase"), which cleaves the Gly-Phe bonds in Met-
      and Leu-enkephalin. SCH 34826 [(S)-N-[n-[1-[(2,2-dimethyl-1,3-dioxolan-4-
      yl)methoxy]carbonyl]-2-phenylethyl]-L-phenyl-alanine-B-alanine] is a potent,
      highly specific, enkephalinase inhibitor that has marked analgesic effects in
      laboratory rodents. The present study compared the effects of SCH 34826 on
      nociception and restraint stress-induced opioid analgesia in reproductive adult
      male and female deer mice, Peromyscus maniculatus. SCH 34826 had significantly
      greater antinociceptive actions and facilitatory effects on stress-induced
      analgesia in male than female mice. These antinociceptive effects of SCH 34826
      were reduced by the general opioid antagonist naloxone and completely blocked by
      the specific delta opioid receptor antagonist, ICI 174,864, and nonsignificantly
      affected by the mu and kappa opioid receptor antagonists, beta-funaltrexamine and
      nor-binaltorphimine, respectively. These results show that there are sex
      differences in the effects of the enkephalinase inhibitor, SCH 34826, on opioid
      mediated antinociception and that these sex differences are associated with delta
      opioid mechanisms.

PMID- 8309955
TI  - A nonferrous instrumental joystick device for recording behavioral responses
      during magnetic resonance imaging and spectroscopy.
AB  - A nonferrous joystick device was developed to permit subjects to continuously
      report ethanol-induced alterations in subjective mood states while undergoing a
      magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)
      procedure. The device utilizes air pressure (supplied by a small compressor) that
      is directed to a series of tubes that terminate in a hand-held unit. The hand
      held unit easily fits inside the magnet and resembles a standard computer game
      joystick except that the ends of the air hoses replace the buttons. The control
      unit contains three pressure transducers, which are triggered when the tubes are
      occluded by the subject, activating different pens on an event marker located 6 m
      from the whole body imager. The unit is safe to use inside a 1.5-Tesla magnetic
      field and does not disrupt the MRI and MRS recording procedures. Subjective
      reports of ethanol-induced euphoria and intoxication paralleled the MRS detection
      of ethanol in the brain. This device could prove to be useful in numerous
      behavioral studies involving whole-body MRI and MRS.

PMID- 8309956
TI  - Centrally administered bacterial lipopolysaccharide depresses feeding in rats.
AB  - Bacterial lipopolysaccharide (LPS) suppresses feeding in rats when administered
      peripherally in the microgram range. In the present study, the effects of LPS
      (Escherichia coli serotype 0111:B4) on the central regulation of feeding in rats
      maintained ad lib was investigated. Intracerebroventricular (ICV) microinfusion
      of LPS (0.1 to 1000 ng/rat) suppressed the short-term (2-h) and long-term
      (nighttime and total daily) food intakes, dose dependently. Computerized analysis
      of behavioral patterns demonstrated a significant reduction of meal size during
      the nighttime, whereas meal frequency and meal duration were also decreased, but
      not significantly. Water intake and locomotor activity also decreased.
      Intraperitoneal administration of LPS in doses equivalent to those administered
      centrally had no effect on food intake. The results suggest that centrally
      administered LPS acts directly in the central nervous system (CNS) to depress
      feeding.

PMID- 8309957
TI  - Vacuous jaw movements in rats induced by acute reserpine administration:
      interactions with different doses of apomorphine.
AB  - Two experiments were conducted to study the vacuous jaw movements induced in rats
      by acute administration of the monoamine-depleting agent reserpine. In the first
      experiment, different doses of reserpine (1.25, 2.5, and 5.0 mg/kg) were assessed
      for their ability to induce vacuous jaw movements. Acute administration of
      reserpine induced a dose-related increase in vacuous jaw movements, with the two
      highest doses being significantly different from the vehicle control. In the
      second experiment, interactions between 5.0 mg/kg reserpine and the dopamine
      agonist apomorphine were investigated. Coadministration of reserpine with the
      lowest dose of apomorphine (0.1 mg/kg) significantly increased vacuous jaw
      movements relative to reserpine alone. The two higher doses of apomorphine (0.5
      and 1.0 mg/kg) significantly decreased vacuous jaw movements in reserpine-treated
      rats. These results demonstrate that vacuous jaw movements are induced by acute
      reserpine treatment in a dose-related manner. In addition, the interactions with
      apomorphine suggest that vacuous jaw movements are stimulated by decreases in
      dopamine release produced by low doses of apomorphine that are thought to have
      mainly presynaptic actions, but that these movements are decreased by higher
      doses of apomorphine that are known to act postsynaptically.

PMID- 8309958
TI  - The potent free radical scavenger alpha-lipoic acid improves memory in aged mice:
      putative relationship to NMDA receptor deficits.
AB  - alpha-Lipoic acid (alpha-LA) improved longer-term memory of aged female NMRI mice
      in the habituation in the open field test at a dose of 100 mg/kg body weight for
      15 days. In a separate experiment, no such effect could be found for young mice.
      alpha-LA alleviated age-related NMDA receptor deficits (Bmax) without changing
      muscarinic, benzodiazepine, and alpha 2-adrenergic receptor deficits in aged
      mice. The carbachol-stimulated accumulation of inositol monophosphates was not
      changed by the treatment with alpha-LA. These results give tentative support to
      the hypothesis that alpha-LA improves memory in aged mice, probably by a partial
      compensation of NMDA receptor deficits. Possible modes of action of alpha-LA
      based on its free radical scavenger properties are discussed in relation to the
      membrane hypothesis of aging.

PMID- 8309959
TI  - Comparison of the effects of pretreatment with competitive or noncompetitive NMDA
      antagonists on vestibular compensation.
AB  - Unilateral labyrinthectomy (UL) results in a syndrome of ocular motor and
      postural disorders which abates over time in a process of behavioural recovery
      known as vestibular compensation. We have previously reported that a single
      systemic pre-UL injection of the organic Ca2+ channel antagonist verapamil or the
      noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 reduces the
      behavioural effects of UL in guinea pigs. The present study was conducted to
      determine if similar effects would be obtained with single injections of the
      competitive NMDA receptor antagonists 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1
      phosphonic acid (CPP) or cis-4-(phosphonomethyl)-piperidine-2-carboxylic acid
      (CGS 19755). Guinea pigs received an IP injection of 5 mg/kg CPP 2.5 h pre-UL, 5
      or 10 mg/kg CPP 1 h pre-UL, 10 or 20 mg/kg CGS 19755 1 h pre-UL, or 1 ml/kg
      vehicle (saline) 1 h pre-UL, and the effects on the compensation of spontaneous
      nystagmus were measured over the following 52 h post-UL. Pretreatment with CPP
      had no significant effect on spontaneous nystagmus frequency or its compensation
      over 52 h post-UL. However, pretreatment with CGS 19755 resulted in a significant
      decrease in spontaneous nystagmus frequency without any acceleration of the rate
      of compensation.

PMID- 8309960
TI  - Naltrexone in vivo protects mu receptors from inactivation by beta
      funaltrexamine, but not kappa receptors from inactivation by nor-binaltorphimine.
AB  - The ability of the competitive opioid antagonist, naltrexone, to protect opioid
      receptors from inactivation by the nonequilibrium antagonists, beta
      funaltrexamine (beta-FNA) and nor-binaltorphimine (nor-BNI), was examined in
      vivo. Male rats were injected SC with 10 mg/kg naltrexone or saline, 30 min
      before being injected intracisternally (IC) with water, 10 micrograms beta-FNA,
      or 1.0 or 10 micrograms nor-BNI. The rats were tested for analgesic responses to
      either U69,593 (nor-BNI groups) or morphine (beta-FNA groups), on a 50 degrees C
      hot plate, 24 h later. Morphine produced dose-related increases in the latency to
      paw lick in rats that received water (IC) (mean ED50 = 3.2 mg/kg). Little or no
      analgesia occurred after 1.0-30 mg/kg of morphine in animals that had received
      saline (SC) and 10 micrograms beta-FNA (IC) 24 h earlier. Pretreatment with 10
      mg/kg naltrexone attenuated the antagonist effects of beta-FNA (morphine ED50 =
      10.8 mg/kg). U69,593 also produced analgesia in animals that received water (IC)
      (ED50 = 0.97 mg/kg). This analgesia was dose-dependently blocked by nor-BNI for
      up to 7 days. Naltrexone did not inhibit the actions of nor-BNI. Thus, naltrexone
      prevented inactivation of mu receptors by beta-FNA but not inactivation of kappa
      receptors by nor-BNI, suggesting that antagonist interactions with mu receptors
      are different from those with kappa receptors.

PMID- 8309961
TI  - Opioid modulation of amphetamine-stimulated dopamine release and concentration in
      rat striatal slices.
AB  - The effects of morphine and naltrexone on amphetamine-stimulated release and
      total concentration of dopamine (DA) from rat striatal slices in vitro were
      examined in this study. Adult male Sprague-Dawley rats were sacrificed and the
      striata were dissected, sliced, and then incubated in buffer solution at 37
      degrees C with amphetamine in the presence or absence of various concentrations
      of morphine, naltrexone (or both), or the dihydroxyphenylalanine (DOPA)
      decarboxylase inhibitor (NSD-1015). The concentrations of DOPA, DA, and
      dihydroxyphenylacetic acid (DOPAC) in the tissue slices and buffer media were
      measured by HPLC/EC. Amphetamine enhanced DA release and also increased total DA
      concentrations. However, neither morphine nor naltrexone alone altered DA
      concentration in the media or tissue slices relative to control (no drug added).
      Moreover, neither morphine nor naltrexone at 1, 10, or 100 microM altered
      amphetamine-stimulated DA release. However, morphine (1 or 10 microM) inhibited
      the amphetamine-stimulated increase in total concentration of DA. This effect of
      morphine was blocked by naltrexone. NSD-1015 alone or in combination with
      morphine did not alter amphetamine-stimulated DA release, but significantly
      reduced DA concentration in striatal slices. NSD-1015 alone also increased DOPA
      accumulation in both media and tissue slices, and this effect was inhibited by
      the addition of morphine. These results indicate that morphine inhibits the
      amphetamine-stimulated increase in total DA content, but not the amphetamine
      stimulated release of DA.

PMID- 8309962
TI  - Concurrent acute exercise alters central and peripheral responses to
      physostigmine.
AB  - This study reports the modulatory effects of physostigmine (Phy) and concurrent
      acute exercise on the time course of cholinesterase (ChE) activity, the rate of
      decarbamylation (Kd), and half-time of recovery of ChE in red blood cells (RBC)
      and various tissues of rats. Acute exercise equivalent to 80% VO2-max (maximal
      oxygen consumption) transiently increased the RBC ChE activity, whereas Phy
      decreased ChE activity in RBC and various tissues. Physostigmine along with
      concurrent acute exercise increased the Kd in RBC, brain, and heart by 56.4%,
      66.7%, and 139%, respectively, compared to Phy alone. The Kd in diaphragm and
      muscle decreased to 14.1% and 56.2%, respectively, compared to Phy alone. The
      variation in Kd might be due to the effect of concurrent acute exercise on the
      redistribution of Phy in various tissues of rat as a result of changes in blood
      flow.

PMID- 8309963
TI  - Effect of cocaine on the production of puberty-accelerating pheromone by male
      mice.
AB  - This study examined whether chronic cocaine exposure could reduce reproductive
      fitness of adult male mice by interfering with their production of the puberty
      accelerating pheromone, an androgen-dependent urinary pheromone that accelerates
      puberty in juvenile female mice. Administered at a high dose of 60 mg/kg body
      weight/day, cocaine caused mortality, body weight loss, and suppression of
      circulating testosterone during the first week of treatment. However, at 40
      mg/kg/day, it resulted in little adverse effect on these parameters. Animals
      showed habituation to repeated cocaine exposure by regaining part of the lost
      weight and reelevating suppressed testosterone level at later stages of
      treatment. Urine samples collected from animals receiving 60 mg/kg cocaine daly
      for 2 weeks lost the puberty-accelerating effect. However, neither a 3-day
      treatment of the same dose nor a lower dose of 40 mg/kg reduced the
      effectiveness. The diminished effect of cocaine-treated male mouse urine might
      reflect lowered testosterone levels with a lag of 10 to 15 days, similar to that
      of castrated male mouse urine. These results indicate that cocaine has no direct
      effect on the production of priming pheromone, and its metabolites in the urine
      did not affect the response of juvenile females to the pheromone.

PMID- 8309964
TI  - The effects of methionine-enkephalin and its related metabolites upon the
      duration of the dorsal immobility response in rats.
AB  - The effects of SC injections of methionine-enkephalin (Met1-5-Enk) and its N
      terminal and C-terminal fragments upon the duration of the dorsal immobility
      response (DIR) over a 60-min time course were investigated. Experiment 1 analyzed
      the effects of various dosages (0.00-100.0 micrograms/kg) on DIR resulting in a
      potentiation of the duration in a dose-time course function. The effects of
      various fragments of Met1-5-Enk (10.0 micrograms/kg) from the N-terminal in
      Experiment 2 and from the C-terminal in Experiment 3 on the DIR resulted in the
      potentiation of the duration with the Met2-5-Enk and Met1-3-Enk fragments. All
      other fragments were not significant. The results were discussed in reference to
      the processing and metabolism of Met1-5-Enk.

PMID- 8309965
TI  - Haloperidol-induced blockade of induction of long-term potentiation in perforant
      path-dentate gyrus pathway in chronically prepared rabbits.
AB  - We investigated the effects of the representative neuroleptic and dopamine
      receptor antagonist haloperidol (HPD) on the induction of long-term potentiation
      (LTP) or on the previously induced LTP in the perforant path-dentate gyrus
      pathway in chronically prepared rabbits. The IP HPD injection of 0.8 mg/kg
      blocked the induction of LTP when it was given before LTP-inducing tetanic
      stimulations, although this dose showed virtually no effect on the baseline
      control responses in the perforant path-dentate gyrus pathway to single shocks.
      However, neither 0.8-mg/kg nor 1.6-mg/kg HPD doses affected the previously
      induced LTP. The possible mechanisms underlying these results, notably the HPD
      induced blockade of LTP induction, are discussed, especially in association with
      the inhibitory action of HPD on calmodulin-mediated events rather than
      dopaminergic function.

PMID- 8309966
TI  - The nucleus accumbens is a site of action for the inhibitory effect of ritanserin
      on ethanol intake in rats.
AB  - The present study evaluated the effect of central injections of the 5-HT2/1C
      receptor antagonist, ritanserin, on ethanol intake in rats with developed
      preference for 3% ethanol. Intracerebroventricular (ICV) injections of ritanserin
      (10 micrograms/rat/day for 10 days) decreased ethanol preference, while
      subcutaneous (SC) treatment with the same dose was ineffective. Ritanserin ICV, 1
      microgram/rat/day, did not reduce alcohol preference. Bilateral injections of
      ritanserin into the nucleus accumbens (NAC; 0.5 microgram/site/day for 10 days)
      produced a prompt and very pronounced suppression of ethanol preference, without
      affecting total fluid intake. Bilateral injections of ritanserin (0.5
      microgram/site/day for 10 days) into the ventral tegmental area (VTA) or into the
      medial prefrontal cortex (MPC) evoked only slight and variable reduction of
      ethanol preference. Injections of ritanserin, 5 micrograms/site/day, into the VTA
      gave a nonselective suppression of the ingestive behavior. The present results
      provide evidence for a central site of action for the effect of ritanserin on
      ethanol intake and suggest that the NAC might be a highly sensitive site for its
      action. Since the NAC is a major target of the mesolimbic dopaminergic system,
      they also suggest that the effect of ritanserin might be due to interference with
      this system.

PMID- 8309967
TI  - Long-term effects of postnatal hypoxia and flunarizine on the dopaminergic
      system.
AB  - Long-term changes of learning behavior and of the striatal dopaminergic system
      were observed in a rat model of early postnatal hypoxia. Striatal dopamine (DA)
      concentration, K(+)-stimulated DA release from slices, and DA uptake into crude
      synaptosomal preparations (S1 fractions) were used as markers of the striatal
      DAergic system. Active avoidance learning was tested as behavioral criterion.
      Cyclodextrin and flunarizine were found to produce long-term effects on the
      DAergic system in control animals. While cyclodextrin normalized hypoxia-induced
      effects in DA release, flunarizine prevented those in DA uptake and improved
      avoidance learning.

PMID- 8309968
TI  - Effects of (-)-pindolol and SDZ 216-525 on social and agonistic behavior in mice.
AB  - In view of conflicting results reported for 5-HT1A receptor involvement in murine
      social conflict, this study examined the effect of two compounds, SDZ 216-525 and
      (-)-pindolol, on agonistic and social behavior in male mice. In a resident
      intruder paradigm, (-)-pindolol (1.0-20.0 mg/kg), a beta-adrenergic 5-HT1A/1B
      antagonist, significantly attenuated all agonistic behaviors across the dose
      range employed. Social behaviors showed significant decreases, while nonsocial
      cage exploration showed significant increases at all doses. Defensive evade was
      significantly attenuated at 20.0 mg/kg. SDZ 216-525 (0.025-1.0 mg/kg), a
      selective 5-HT1A antagonist, significantly attenuated offensive posturing and
      bite-attacks at 1.0 mg/kg, and all offensive behaviors nonsignificantly at the
      smaller doses tested. Rearing was significantly attenuated at 1.0 mg/kg, while
      cage exploration increased at this dose. Defensive and social behaviors remained
      largely unchanged. These results show that both compounds tested produced
      significant reductions in offensive behavior, with concomitant changes in
      defensive, social, and nonsocial behaviors. Results are discussed in relation to
      SDZ 216-525 and (-)-pindolol potential for the control of anxiety and agonistic
      behavior.

PMID- 8309969
TI  - The role of dopamine and AMPA/kainate receptors in the nucleus accumbens in the
      hypermotility response to MK801.
AB  - The purpose of this study was to evaluate the role of endogenous dopamine in the
      hypermotility response to MK801. The administration of MK801 (0.1 mg/kg, SC) to
      rats produced an intense stimulation of coordinated locomotor activity, which was
      not associated with stereotyped behavior. This stimulatory response was inhibited
      by pretreatment with either reserpine (5 mg/kg, IP) or alpha-methyl-p-tyrosine (2
      doses of 250 mg/kg, IP). Similarly, pretreatment with the D2 antagonist
      eticlopride (0.03 mg/kg, SC) or the D1 antagonist SCH23390 (0.1 mg/kg, SC)
      produced a marked inhibition of MK801-stimulated hypermotility, and the
      combination of eticlopride (0.03 mg/kg, SC) and SCH23390 (0.03 mg/kg, SC)
      produced a greater inhibition of MK801-stimulated locomotion than either agent
      alone. The administration of SCH23390 or eticlopride directly into the nucleus
      accumbens inhibited the locomotor response to MK801, with the combination of both
      drugs producing a greater inhibition than either agent alone. The intra-accumbens
      administration of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate
      (AMPA)/kainate receptor antagonists DNQX or GAMS also inhibited the locomotor
      response produced by MK801. These data suggest that the activation of D1 and D2
      dopaminergic receptors and AMPA/kainate excitatory amino acid receptors in the
      nucleus accumbens is required for the stimulation of locomotor activity produced
      by MK801.

PMID- 8309970
TI  - Prevention of soman-induced cognitive deficits by pretreatment with human
      butyrylcholinesterase in rats.
AB  - This study examined the ability of pretreatment with human serum
      butyrylcholinesterase (HuBChE) to prevent soman-induced cognitive impairments.
      Behavioral testing was carried out using the Morris water maze task evaluating
      learning, memory, and reversal learning processes. Pretreatment with HuBChE
      significantly prevented the memory and reversal learning impairments induced by
      soman. A small deficiency in performance was observed only during part of the
      learning period in HuBChE-treated rats after administration of soman. Results
      support the contention that pretreatment alone with HuBChE is sufficient to
      increase survival and to prevent impairment in cognitive functioning following
      exposure to soman.

PMID- 8309971
TI  - Pharmacological studies of centrifugation-induced analgesia.
AB  - Subjecting rats to a brief period of centrifugal rotation produces a brief
      analgesia (1-2 min) that is similar to that produced by pretreatment with
      morphine. The effect of the morphine is blocked by naloxone, while that of the
      centrifugal rotation is only partially blocked by the same dose of naloxone.
      Cholinergic blocking agents such as scopolamine are also capable of partially
      blocking the rotational-induced analgesia. The combination of pretreatment with
      scopolamine plus naloxone is capable of completely blocking the rotational
      induced analgesia, suggesting the involvement of both central cholinergic and
      endogenous opioid components.

PMID- 8309972
TI  - Naloxone's anorectic effect is dependent upon the relative palatability of food.
AB  - It has been suggested that opioids modify food intake by enhancing palatability.
      In the present series of studies we evaluated the effect of naloxone on food
      intake of a preferred food (chocolate chip cookies), normal rat chow, and an
      "aversive" food (high fiber chow). We found that naloxone decreased 18- and 48-h
      deprivation-induced intake of chocolate chip cookies much more potently than that
      of chow, when these foods were presented on separate occasions. When these foods
      were presented concurrently, this difference in naloxone's potency was no longer
      apparent. When rats were offered high fiber chow, only the 10 mg/kg dose of
      naloxone decreased intake. In these same rats naloxone significantly decreased
      normal chow intake at a dose of 0.1 mg/kg. Thus, naloxone's ability to decrease
      food intake appears to be dependent upon the palatability of the food.

PMID- 8309973
TI  - Propranolol-induced increases in target-biting attack.
AB  - The effect of a beta-adrenoreceptor blocking agent on defensive aggression in
      mice was evaluated. Acute doses of d,l-propranolol (0.2, 0.4, 0.8, 1.6, 3.2, 6.4,
      and 12.8 mg/kg) were administered to male Rockland-Swiss mice prior to testing in
      a target-biting paradigm. Baseline conditions established a high target-biting
      rate low biting rate during a 15-s tone stimulus preceding the next shock. Every
      dose of propranolol increased target-biting rates above baseline during each
      interval with one exception: 0.4 mg/kg decreased the biting rate immediately
      after delivery of the tail shock. The overall increase in aggression observed
      following dosing with propranolol was not expected from a review of the clinical
      literature. These results are discussed in reference to propranolol's known
      effects on the brain serotoninergic systems and the use of an animal model of
      defensive aggression.

PMID- 8309974
TI  - Reinforcing effects of extended inhalation of a low nitrous oxide concentration
      in humans.
AB  - The reinforcing, subjective, and psychomotor effects of 30 min of inhalation of
      20% nitrous oxide were determined in 12 healthy volunteers using a choice
      paradigm with 100% oxygen as placebo. Nitrous oxide was chosen on only 22% of
      choice occasions, indicating that, in general, this concentration did not
      function as a reinforcer. Nitrous oxide produced changes in mood, but had no
      effect on psychomotor performance. Three out of the 12 subjects chose nitrous
      oxide on at least two out of the three choice sessions, and during a poststudy
      debriefing interview, reported pleasant effects of the drug. The other nine
      subjects reported unpleasant acute effects of the drug (e.g., drowsiness) or
      residual (postsession) effects of the drug which, they said, influenced their
      drug choice. The present results are compared to those results obtained in a
      previous study in which higher concentrations of nitrous oxide (30 and 40%) also
      produced relatively low choice rates. The apparent lack of reinforcing effects of
      extended inhalation of nitrous oxide is discussed.

PMID- 8309975
TI  - Different effects of nucleus accumbens and ventrolateral striatal dopamine
      depletions on instrumental response selection in the rat.
AB  - This experiment was undertaken to investigate dopaminergic involvement in food
      related instrumental behavior. Rats were tested in an operant chamber in which
      there was a choice between pressing a lever to receive a preferred food (Bioserve
      pellets) or feeding upon a less preferred food (lab chow). The lever-pressing
      schedule was a fixed ratio 5 (FR5). Rats usually pressed the lever at high rates
      to obtain the preferred food, and typically ate little of the lab chow even
      though it was freely available in the chamber concurrently with the lever
      pressing schedule. The neurotoxic agent 6-hydroxydopamine was injected directly
      into the nucleus accumbens, medial striatum, or ventrolateral striatum to
      determine the effects of dopamine depletion on the performance of this task.
      Depletion of dopamine in the nucleus accumbens led to a dramatic shift in
      behavior in which there was a significant decrease in lever pressing but a
      significant increase in consumption of lab chow. The shift away from lever
      pressing and towards chow consumption in rats with accumbens DA depletions was
      significantly correlated with a decrease in spontaneous locomotor activity.
      Dopamine depletions in the medial striatum did not significantly affect lever
      pressing or chow consumption. Ventrolateral striatal dopamine depletions
      decreased lever pressing but also tended to reduce consumption of lab chow. Rats
      with ventrolateral striatal dopamine depletions also showed profound deficits in
      home-cage feeding, and these rats had to receive wet mash or tube feeding to
      maintain body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8309976
TI  - Inhibition of nitric oxide (NO) production selectively impairs learning and
      memory in the rat.
AB  - Animals administered the nitric oxide (NO) synthase inhibitor N-w-nitro-L
      arginine methyl ester (NAME) for five days exhibited severe deficits in
      acquisition of a place-navigation learning task. The effect of NAME was selective
      to place-navigation learning. NAME had no effect on sensorimotor or motivational
      processes in a related task. These results are consistent with the view that NO
      participates in learning and execution of memory tasks.

PMID- 8309977
TI  - Discriminative stimulus properties of midazolam are shared by a GABA-receptor
      positive steroid.
AB  - 3-Alpha-5-alpha-tetrahydrodeoxycorticosterone (alloTHDOC) is a 3-alpha ring A
      reduced metabolite of deoxycorticosterone that has been shown to act via
      nongenomic mechanisms to modulate the GABAA receptor complex allosterically in
      vitro. Moreover, there are behavioral data consistent with the anxiolytic actions
      of GABA-receptor positive steroids. The drug discrimination paradigm was used in
      rats to demonstrate that effects of alloTHDOC are mediated by the GABAA receptor
      complex in the intact animal. In rats trained to discriminate 1.8 mg/kg of
      midazolam from saline, alloTHDOC substituted for the training stimulus.

PMID- 8309978
TI  - In vivo electrochemical studies of gradient effects of (SC) cocaine on dopamine
      and serotonin release in dorsal striatum of conscious rats.
AB  - Cocaine (20 mg/kg) was administered subcutaneously (SC) to conscious male Sprague
      Dawley rats after exploration in a novel chamber. (SC) cocaine was studied for
      its influence on in vivo dopamine (DA) and serotonin (5-HT) release in dorsal
      striatum (STr), with a further study of an anterior-posterior dorsal subdivision
      in a range of +/- 400 microns. Semiderivative voltammetry, a circuit for in vivo
      electrochemical biotechnologies, was used in combination with a stearate
      microelectrode to concurrently detect in separate electrochemical signals the
      electroactive species for DA and 5-HT in dorsal STr. The temporal resolution for
      detection was in the order of seconds. Concomitantly, cocaine-induced
      psychostimulant behaviors were studied with infrared photo beam detection.
      Psychostimulant behaviors classically thought to depend on DA--that is,
      hyperactivity (increased locomotor activity or ambulations), rearing, and finally
      stereotypy (fine movements of grooming and head bob)--and a 5-HT-ergic behavior,
      central ambulations, were monitored. The results showed that (SC) cocaine
      significantly (p < 0.0001) increased DA release in dorsal STr, whereas the
      overall effect of (SC) cocaine on 5-HT release was a significant increase (p <
      0.0001) followed by an overall small (13%) but statistically significant decrease
      (p < 0.05). A dramatic cocaine-induced gradient effect on 5-HT release was seen
      in anterior-posterior dorsal STr, where 5-HT release was significantly (p <
      0.0001) increased throughout the entire time period of study. Classically DA
      dependent behaviors were significantly and positively correlated with increased
      DA release in dorsal STr and anterior-posterior dorsal STr (p < 0.001) in the 4-h
      period of study. However, 5-HT release after cocaine in the anterior-posterior
      dorsal STr was significantly and positively correlated with the classically DA
      dependent behaviors as well (p < 0.001), implicating a role for 5-HT in the
      effectuation of cocaine-induced psychostimulant behavior. Generally, the 5-HT
      ergic response to cocaine was enhanced before the DA-ergic response. Therefore,
      the data show that 5-HT as well as DA plays a role in the underlying mechanism of
      action of cocaine in dorsal STr. The data suggest that 5-HT may play a
      compensatory or adaptive role in the modulation of cocaine-induced nigrostriatal
      DA-ergic regulation.

PMID- 8309979
TI  - Voluntary alcohol consumption in vervet monkeys: individual, sex, and age
      differences.
AB  - The patterns of voluntary alcohol consumption were studied in 35 vervet monkeys
      (Cercopithecus aethiops), classified into four groups. Each monkey showed a
      fairly steady rate during the studied period, resulting in individual differences
      that became more evident as the treatment evolved. Females showed higher alcohol
      intake frequencies than males. This sexual difference was maintained among adults
      and juveniles. Age differences were also observed: juveniles showed higher
      frequencies of intake than adults, both in general and in each sex group. Intake
      frequency was not related to age in prepubertal subjects, neither in general nor
      in each particular sex. The origin of these sex and age alcohol consumption
      differences remains to be studied, but differences in alcohol metabolism and
      factors related to puberty are possible influences.

PMID- 8309980
TI  - Effects of the dopamine release inhibitor, CGS 10746B, on the locomotor stimulant
      and discriminative stimulus effects of cocaine and methamphetamine.
AB  - CGS 10746B or 5-(4-methyl-1 piperazinyl)-imadazo[2,1-b]1,3,5]benzothiadiazepine
      maleate is a clozapine analog that, unlike clozapine, produces decreases in
      neostriatal dopamine release without changing dopamine metabolism or occupying D2
      receptors. CGS 10746B also blocks neuronal impulse flow. The ability of this
      atypical antipsychotic candidate to alter the discriminative stimulus effects
      induced by cocaine or methamphetamine in rats or the stimulation of locomotor
      activity in mice was evaluated. A range of doses of CGS 10746B was tested against
      maximally effective doses of the psychomotor stimulants. Although CGS 10746B
      completely blocked the locomotor stimulant effects of cocaine and
      methamphetamine, it also decreased spontaneous activity in mice over the same
      dose range. Rats were trained to discriminate 10 mg/kg cocaine or 1 mg/kg
      methamphetamine from saline. The discriminative stimulus effects of cocaine or
      methamphetamine were not blocked by CGS 10746B. Thus, in contrast to other
      potential atypical antipsychotic compounds (e.g., D1 receptor antagonists), CGS
      10746B does not appear to produce selective blockade of these behavioral effects
      of psychomotor stimulant compounds.

PMID- 8309981
TI  - Role of endorphins in benzodiazepine-induced hyperglycaemia in mice.
AB  - The possibility that benzodiazepine-induced hyperglycaemia is mediated through
      the release of endogenous endorphins was tested. The results show that naloxone,
      the opiate antagonist, potentiated clonazepam-induced hyperglycaemia. Treatment
      with increasing doses of morphine for six days, which induced tolerance to
      endorphins, did not affect clonazepam-induced hyperglycaemia. The results
      indicate that endorphins do not mediate benzodiazepine-induced hyperglycaemia.

PMID- 8309982
TI  - 5-HT1A receptors mediate the effect of the bulbospinal serotonin system on spinal
      dorsal horn nociceptive neurons.
AB  - The present study examined whether the effect of stimulation of the nucleus raphe
      magnus (NRM) is mediated by spinal cord dorsal horn serotonin1A (5-HT1A)
      receptors in the rat. This hypothesis predicts that nociceptive dorsal horn units
      inhibited by NRM stimulation or iontophoretic 5-HT application would also be
      inhibited by iontophoresis of the selective 5-HT1A agonists 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) and buspirone. A total of 78 dorsal horn wide
      dynamic-range neurons were recorded. Overall, 62% of the cells tested (48/78)
      were responsive to electrical stimulation of the NRM with the predominant
      response being inhibitory (38/48; 79%). Fifty-eight cells were tested for their
      response to both NRM stimulation and 8-OH-DPAT iontophoresis: 20/58 cells were
      inhibited by NRM stimulation and 50% of the cells inhibited by NRM stimulation
      were also inhibited by 8-OH-DPAT. Fifty-two cells were tested for their response
      to both NRM stimulation and buspirone iontophoresis: 14/52 cells were inhibited
      by NRM stimulation with 9/14 similarly inhibited by buspirone. To examine whether
      exogenously applied serotonin produced an effect through 5-HT1A receptors, the
      effect of both 5-HT and 8-OH-DPAT iontophoresis was tested on 57 dorsal horn
      neurons. The majority of cells (25/57) were inhibited by 5-HT application; 15/25
      were similarly inhibited by 8-OH-DPAT. The response of 48 dorsal horn cells to 5
      HT and buspirone iontophoresis was compared. Forty-four percent (21/48) of the
      cells were inhibited by 5-HT; 16/21 were also inhibited by buspirone.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8309983
TI  - The effect of immunomodulator muramyl dipeptide on serotoninergic responses of
      isolated neuromuscular preparations.
AB  - The mode of action of muramyl dipeptide (MDP), a compound with
      immunopharmacological properties, was studied in isolated nerve smooth muscle
      preparations with different receptor systems. The amplitudes of contractions
      evoked directly by stimulants as well as neurogenic twitches or relaxations were
      registered. In the rat stomach strip EC50 of acetylcholine, serotonin (5-HT) and
      KCl was estimated. MDP (50 nmol/l) but not levamisole potentiated selectively the
      contractions evoked by 5-HT and significantly (p < 0.01) lowered the respective
      EC50. In the rat vas deferens MDP selectively potentiated the twitches enhanced
      by 5-HT but not those enhanced by noradrenaline. Such potentiation was blocked by
      5-HT3 antagonists tropisetron and MDL 72,222 (1 alpha H,3 alpha,5 alpha-H-tropan
      3-yl 3,5-dichlorobenzoate) but not by the 5-HT2 antagonist ketanserin. The
      antagonist methiothepin nonselectively abolished the potentiation by MDP as well
      as the enhancement of twitches by 5-HT and noradrenaline, whereas l-propranolol
      and isamoltan influenced neither the enhancement of twitches by 5-HT nor the
      potentiation by MDP. In the isolated longitudinal muscle of guinea pig proximal
      colon, 5-HT caused a biphasic response in the presence of atropine; the initial
      neurogenic relaxation was potentiated in the presence of MDP and was suppressed
      in the presence of tropisetron. Thus, the potentiating effect of MDP in the
      isolated organs studied was selective with respect to the serotoninergic system
      and might be mediated by 5-HT3 receptors.

PMID- 8309984
TI  - Hyperpolarizing afterpotentials in C fibers and local anesthetic effects of
      clonidine and lidocaine.
AB  - Effects of clonidine and lidocaine on the hyperpolarizing after-potential (HAP)
      and frequency-dependent block in C fibers were examined on desheathed rabbit
      vagus nerves, using the sucrose gap technique. A single action potential (AP) was
      followed by a fast and a slow HAP. Clonidine, at concentrations from 0.05 to 50
      mumol/l, decreased the fast HAP, while the AP amplitude was unchanged. At a 500
      mumol/l concentration of clonidine, the fast HAP amplitude was similar to
      control, the slow HAP was increased, and the AP amplitude decreased. Lidocaine at
      500 mumol/l delayed and broadened the HAP, making a distinction between fast and
      slow HAP impossible, and decreased and delayed the AP amplitude. In the presence
      of lidocaine (500 mumol/l), clonidine at concentrations from 0.05 to 500 mumol/l
      decreased the HAP amplitude, without modifying the lidocaine-induced shape of the
      HAP. The modifications of the HAP, however, do not contribute to the local
      anesthetic effects of clonidine, as the addition of clonidine (0.5 and 500
      mumol/l) to Locke or lidocaine (500 mumol/l) solution does not enhance the
      frequency-dependent block (3 and 10 Hz) observed with either Locke or lidocaine
      solution alone.

PMID- 8309985
TI  - Sodium ions modulate differentially the effect of a benzodiazepine agonist on rat
      spinal mu-, delta- and kappa-opioid receptors.
AB  - Midazolam, a benzodiazepine receptor agonist, when injected intrathecally either
      enhances or decreases antinociception produced by intrathecal administration of
      morphine in rats. Furthermore, midazolam inhibits binding of several opioid
      ligands to spinal opioid receptors in vitro [Rattan et al, Anesth Analg
      1991;73:124-131]. This study was designed to investigate the effect of midazolam
      on binding of mu-, delta- and kappa-ligands to rat spinal opioid receptors in the
      presence of sodium ions which differentially modulate binding of opioid agonists
      and antagonists. Sodium ions (50-1,000 mmol/l) selectively increased the specific
      binding of [3H]naloxone but decreased binding of opioid agonists such as [3H]DAGO
      (Tyr-D-Ala-Gly-Methyl-Phe-Gly-ol-enkephalin) to mu-receptors, [3H]DSTLE (Tyr-D
      Ser-Gly-Phe-Leu-Thr-enkephalin) to delta-receptors and [3H]EKC
      (ethylketocyclazocine) to kappa-receptors in rat spinal cord in vitro. Midazolam
      (1-100 mumol/l) inhibited the binding of [3H]naloxone, [3H]DAGO, [3H]DSTLE and
      [3H]EKC. Sodium ions (100 mmol/l) antagonized the inhibition of binding of
      [3H]naloxone and [3H]DSTLE by midazolam by increasing IC50 values for midazolam.
      However, sodium ions potentiated the inhibition of binding of [3H]DAGO by
      midazolam by decreasing IC50 value for midazolam and had a mixed effect on
      binding of [3H]EKC in the presence of midazolam. Scatchard analysis performed in
      the presence of sodium ions and/or midazolam confirmed the specific effects of
      sodium ions as well as midazolam on the Bmax and KD of mu-, delta-, and kappa
      receptors. These results suggest for the first time that sodium ions play an
      important role in the modulation of spinal opioid receptors by benzodiazepines.
      Sodium ions potentiate the inhibition of DAGO binding but antagonize the
      inhibition of naloxone and DSTLE binding by midazolam in rat spinal cord.

PMID- 8309986
TI  - Effect of isoproterenol on the relationship between regional cyclic AMP and local
      coronary blood flow in the canine myocardium.
AB  - This study was designed to test in the dog heart the hypothesis that local levels
      of myocardial cyclic AMP (cAMP) would exhibit significant heterogeneity; that
      this heterogeneity would correlate with local coronary blood flow, and that this
      association would be increased with isoproterenol stimulation. Anesthetized open
      chest dogs were studied during control (n = 7) or isoproterenol (0.5
      micrograms/kg/min) infusion (n = 7) to test this hypothesis. Coronary blood flow
      was measured with radioactive microspheres, and cAMP was determined with a
      competitive binding assay using 3H-cAMP. Significant heterogeneity in cAMP
      existed during basal [592 pmol/g, within-animal coefficient of variation (100 x
      mean/SD) = 45.2%] and isoproterenol stimulated [872 (27.3%)] conditions. Method
      variability could account for only 28% of the total basal variability. No
      correlation between local blood flow [87 ml/min/100 g (12.9%)] and local cAMP was
      found under control conditions. Both coronary blood flow [206 (20.8%)] and cAMP
      levels increased significantly with isoproterenol stimulation. There was a
      significant correlation between normalized stimulated blood flow and cAMP: % flow
      = 0.39 (% cAMP) + 61.3 (r = 0.48, p < 0.0001). We conclude that significant
      heterogeneity in myocardial cAMP levels exists, and that this heterogeneity
      correlates with coronary blood flow heterogeneity during isoproterenol
      stimulation.

PMID- 8309987
TI  - Fantofarone (SR33557): effects on myocardial oxygen consumption and coronary
      blood flow.
AB  - We have investigated the effects of a novel calcium antagonist, fantofarone (SR
      33557) on myocardial oxygen consumption (MO2C) and coronary blood flow in
      anaesthetized dogs during periods of normal and elevated heart rate. 25
      micrograms/kg i.v. fantofarone induced a transient increase in coronary blood
      flow (+25% after 2 min; p < 0.05) and a more sustained decrease in MO2C (-50%
      after 5 min; p < 0.05). During the periods of pacing, these alterations on
      cardiac function were not evident. Administration of 50 micrograms/kg i.v.
      resulted in similar modifications of cardiac function; however, these changes
      were apparent for a longer duration. Coronary blood flow was still significantly
      elevated by 29% 2 min after drug administration (p < 0.01) and MO2C was reduced
      by 67% after 5 min (p < 0.01) and by 56% after 30 min (p < 0.05). Most
      importantly, a significant decrease in MO2C was observed during the pacing
      periods (32% after 10 min; p < 0.01). Thus fantofarone can significantly modify
      cardiac function and in particular, decrease MO2C consumption during periods of
      elevated heart rate.

PMID- 8309988
TI  - Antiulcer and gastroprotective effects of quercetin: a gross and histologic
      study.
AB  - This study was designed to determine the cytoprotective properties of quercetin
      and the involvement of endogenous prostaglandins in mucosal injury produced by
      absolute ethanol. Gastric glands were also analyzed histologically. Oral
      pretreatment with the highest dose of quercetin (200 mg/kg), 120 min before
      absolute ethanol, was most effective in necrosis prevention. Subcutaneous
      administration of indomethacin (10 mg/kg) to the animals treated with quercetin
      (200 mg/kg) partially inhibited gastric protection. All treated groups showed a
      marked increase in the amount of gastric mucus although this increase was less in
      animals pretreated with indomethacin. Total proteins and the hexosamine content
      decreased in the groups receiving indomethacin. The histomorphometric evaluation
      of the gastric damage confirmed a significant increase in mucus production
      accompanied by a parallel reduction of gastric lesions with the highest dose of
      quercetin tested.

PMID- 8309989
TI  - Effect of alpha-interferon on erythrocyte and hepatocyte plasma membranes derived
      from cirrhotic rats.
AB  - Interferons are recognized to inhibit collagen production. Since fibrosis has
      been associated with liver dysfunction, we investigated the effects of alpha
      interferon on the function and lipid composition of hepatocyte and erythrocyte
      plasma membranes derived from CCl4-cirrhotic male Wistar rats. In both cell
      types, CCl4 decreased Na+/K+ and Ca(2+)-ATPase activity and increased the
      cholesterol to phospholipids (CH/PL) ratio (p < 0.05). Administration of
      interferon (80,000 IU/kg s.c. for 8 weeks) increased survival from 40 to 90%, and
      preserved normal ATPase activity and CH/PL ratio. Our results show that
      administration of alpha-interferon to CCl4-cirrhotic rats improves survival, and
      liver and erythrocyte membrane function and composition, probably as a result of
      its antifibrogenic effect.

PMID- 8309990
TI  - Epidemiology of poisoning.
AB  - Despite difficulties in the interpretation of available data, certain general
      observations can be made on the epidemiology of poisioning. Childhood poisoning
      is usually accidental and tends to be associated with a low morbidity and
      mortality. In Western Europe and North America, it is most often due to household
      products and pharmaceuticals; in developing countries, paraffin, traditional
      medicines , snakes bites and insect stings are more commonly involved. In adults,
      self-poisoning is usually deliberate (suicide or parasuicide) and has a higher
      morbidity and mortality rate. Analgesics and psychotropics predominate in Western
      Europe and North America as causes of admission to hospital, though carbon
      monoxide is responsible for most deaths (the majority of which occur outside
      hospital). In developing countries, accidental and deliberate pesticide poisoning
      is probably the commonest cause of adult deaths.

PMID- 8309991
TI  - The potential of protein kinase C as a target for anticancer treatment.
AB  - Many investigators have embarked upon the search for novel cellular targets for
      the treatment of cancer. A popular therapeutic strategy is to intervene with the
      components of cellular signalling systems that are altered during malignancy. The
      molecular heterogeneity of the protein kinase C (PKC) family and their functional
      divergence make them attractive targets for anticancer drug development. PKC can
      also influence the sensitivity of tumor tissue to conventional cytotoxic drugs.
      As discussed in this review, a complete understanding of the PKC signal
      transduction pathway is obligatory for the selective destruction of tumor tissue
      by exploiting PKC as either a target or a modulator of cancer chemotherapeutic
      agents.

PMID- 8309992
TI  - Modification of eukaryotic signaling proteins by C-terminal methylation
      reactions.
AB  - Eukaryotic polypeptides that are initially synthesized with the C-terminal
      sequence -Cys-Xaa-Xaa-Xaa, including a variety of signal-transducing proteins,
      such as small G-proteins, large G-proteins and cGMP phosphodiesterases, can be
      targeted for a series of sequential post-translational modifications. This
      processing pathway includes the isoprenylation of the cysteine residue with a
      farnesyl or geranylgeranyl moiety, followed by proteolysis of the three terminal
      residues and alpha-carboxyl methyl esterification of the cysteine residue. The
      potential reversibility of the last step suggests that it may be involved in
      modulating the function of these proteins. Firstly, methylation may play a role
      in the activation of cellular peptides or proteins. Secondly, this modification
      may aid in the membrane attachment of cytosolic precursor proteins. Thirdly,
      methylation may protect the polypeptide from C-terminal proteolytic degradation
      once the three terminal amino acid residues are removed. Finally, reversible
      methylation may directly regulate the function of its target proteins.
      Therapeutically, inhibitors of C-terminal isoprenylcysteine methylation or
      demethylation reactions may prove to be useful pharmacological tools as anti
      cancer and anti-inflammatory agents.

PMID- 8309993
TI  - Modelling of the passage of drugs into milk.
AB  - Pharmacokinetic modelling of plasma to milk transfer of drugs has assisted our
      understanding of the milk to plasma ratio (M/P) and pitfalls associated with it.
      The most useful way of measuring M/P ratios is, however, by model independent
      analysis. Physiological models have been proposed to enable the prediction of M/P
      ratios. The most accurate in prospective performance is the log-transformed phase
      distribution model. This model, developed by stepwise multiple linear regression
      analysis, also assists in the understanding of the relative contribution of the
      various physiological factors involved in the distribution of drugs into milk.

PMID- 8309994
TI  - Anticoagulants in pregnancy.
AB  - Pregnancy is associated with a prethrombotic state. Pulmonary embolism is the
      major cause of maternal mortality. Anticoagulant prophylaxis and therapy are
      therefore commonplace in pregnant women. Those with inherited and acquired
      thrombophilic conditions are at increased risk and special considerations arise
      in management. Heparin has recently become the favoured anticoagulant drug in
      pregnancy. Its use carries risks of osteopaenia and thrombocytopaenia, as well as
      haemorrhage, in the mother. Warfarin is teratogenic and may also cause
      haemorrhagic complications in mother and fetus. Few clinical trial data exists
      for guidance on optimal anticoagulant regimes during pregnancy and the puerperium
      and details of management will depend upon the personal preferences of patient
      and clinician, after due consideration of the perceived risks and benefits in the
      individual clinical situation.

PMID- 8309995
TI  - Tissue inhibitor of metalloproteinases (TIMP, aka EPA): structure, control of
      expression and biological functions.
AB  - The TIMPs play an important role in regulating the activity of the secreted
      metalloproteinases (collagenases, stromelysins, gelatinases). Two different TIMPS
      have been well characterized, each capable of inhibiting all tested eukaryotic
      metalloproteinases but showing specific binding to a particular gelatinase at a
      site distinct from the active site. They influence the activation of the
      prometalloproteinase and act to modulate proteolysis of extracellular matrix,
      notably during tissue remodeling and inflammatory processes. On certain cell
      types, they can exhibit growth factor-like activity, and they can inhibit the
      tumorigenic and metastatic phenotype of cancer cells.

PMID- 8309996
TI  - Viral protein kinases and protein phosphatases.
AB  - Certain large DNA viruses (e.g. herpesviruses and poxviruses) encode proteins
      related to cellular protein-serine/threonine kinases, and Hepatitis B virus and
      vesicular stomatitis virus may encode structurally different protein kinases.
      Other viruses activate cellular protein kinases, e.g. interferon-induced
      eukaryotic initiation factor-2 kinase, growth factor-induced kinases and protein
      kinases that regulate mitosis. Protein phosphatases are encoded by vaccinia virus
      and bacteriophage lambda and must also play a role in viral infection--as do
      cellular protein phosphatases. The functions of many of these viral enzymes
      remain to be determined, but they represent possible new targets for anti-viral
      therapy.

PMID- 8309997
TI  - Apoptosis during photodynamic therapy-induced ablation of RIF-1 tumors in C3H
      mice: electron microscopic, histopathologic and biochemical evidence.
AB  - Very little is known about the applicability of the metabolic and biochemical
      events observed in cell culture systems to in vivo tumor shrinkage following
      photodynamic therapy (PDT). The purpose of this study was to assess whether PDT
      induces apoptosis during tumor ablation in vivo. We treated radiation-induced
      fibrosarcoma (RIF-1) tumors grown in C3H/HeN mice with PDT employing three
      photosensitizers, Photofrin-II, chloroaluminum phthalocyanine tetrasulfonate, or
      Pc IV (a promising phthalocyanine developed in this laboratory). Each
      photosensitizer was injected intraperitoneally and 24 h later the tumors were
      irradiated with an appropriate wavelength of red light using an argon-pumped dye
      laser. During the course of tumor shrinkage, the tumors were removed at 1, 2, 4
      and 10 h post-PDT for DNA fragmentation, histopathologic, and electron
      microscopic studies. Markers of apoptosis, viz. the ladder of nucleosome-size DNA
      fragments, increased apoptotic bodies, and condensation of chromatin material
      around the periphery of the nucleus, were evident in tumor tissue even 1 h post
      PDT; the extent of these changes increased during the later stages of tumor
      ablation. No changes were observed in tumors given photosensitizer alone or
      irradiation alone. Our data suggest that the damage produced by in vivo PDT may
      activate endonucleolysis and chromatin condensation, and that apoptosis is an
      early event in tumor shrinkage following PDT.

PMID- 8309998
TI  - The effect of acceptor group variation on the solvatochromism of donor-acceptor
      fluorophores.
AB  - The absorption and emission characteristics of five hydroxytetrahydrochrysenes
      substituted with acceptor groups (nitro, cyano, methylketone, 1 degree amide and
      methyl ester) (THC-NO2, THC-CN, THC-COCH3, THC-CONH2 and THC-CO2CH3,
      respectively) were investigated in an extensive set of solvents. The order of
      absorption and fluorescence bathochromicity are: THC-NO2 > THC-COCH3 > THC-CN >
      or = THC-CO2CH3 > THC-CONH2 and THC-NO2 >> THC-COCH3 > THC-CO2CH3 > THC-CN > THC
      CONH2, respectively. The emission spectra of these compounds are sensitive to the
      solvent polarity (ET[30] scale) in the order: THC-NO2 > THC-COCH3 > THC-CO2CH3 >
      THC-CONH2 > THC-CN. The response of the emission maxima of these compounds to the
      solvent polarity and hydrogen-bond donor/acceptor properties (pi */alpha/beta and
      acity/basity scales) was also determined. The emission energies of THC-NO2 were
      most sensitive to pi *, beta, acity, and basity of the solvent; those of the
      amide were least sensitive to the solvent pi *, beta, and basity. The ground- and
      excited-state dipole moments were determined by semiempirical molecular orbital
      calculations and the absorption/fluorescence solvent-shift method, respectively.
      THC-NO2 had the largest ground- and excited-state moments. The ester and amide
      had the smallest ground- and excited-state moments, respectively. In general,
      unsatisfactory results were obtained for correlations of the emission and
      absorption energies, fluorescence solvatochromism and the ground- and excited
      state dipole moments with the Hammett substituent constants of the five acceptor
      groups. Acceptable correlations were obtained for the absorption and emission
      energies and the fluorescence solvatochromism with the substituent constants if
      the cyano compound was excluded.

PMID- 8309999
TI  - Metabolically convertible lipophilic derivatives of pH-sensitive amphipathic
      photosensitizers.
AB  - We propose the use of acetoxymethyl esters of pH-sensitive amphipathic
      photosensitizers (PS) for photodynamic therapy (PDT). These compounds may be
      applicable for PDT involving endocytosis of lipophilic carriers leading to
      lysosomal uptake of the esterified PS by target cells. Partial and/or total
      enzymatic de-esterification may result in the extralysosomal distribution of the
      photoactive agents, possibly culminating in a multisite photochemical response.
      We report here the synthesis and properties of chlorin e6 triacetoxymethyl ester
      (CAME) and pheophorbide a acetoxymethyl ester (PAME). Chlorin e6 and pheophorbide
      a are photocytotoxic chlorins that possess free carboxylate groups and exhibit
      optimum wavelengths of excitation substantially red shifted relative to
      hematoporphyrin derivative. Acetoxymethyl esterification of chlorin e6 and
      pheophorbide a was accomplished with bromomethyl acetate. High-performance liquid
      chromatography allowed for the purification of PAME, in 87% purity, and CAME, in
      63% yield and 94% purity, as well as the detection of the presumed mono- and
      diesters of chlorin e6 as transient intermediates in the synthesis of CAME. The
      ultraviolet-visible absorption, fluorescence excitation and emission, NMR and
      mass spectra of the chlorin e6 triester are consistent with those expected for
      CAME. The pH-sensitive amphipathicity of pheophorbide a and chlorin e6 but not
      CAME was demonstrated using a water/1-octanol partition assay. The production of
      pheophorbide a from PAME and the sequential formation of the di- and monoesters
      and free chlorin e6 from CAME, by the action of lysosomal esterases obtained from
      cancer cells, demonstrate the potential of cellular enzymes to convert the
      lipophilic esters to pH-sensitive amphipathic PS.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8310000
TI  - 8-methoxypsoralen plus UVA induces the 72 kDa heat shock protein in organ
      cultured normal human skin.
AB  - The proteins induced by heat and other stressors, called heat shock proteins
      (HSP) or stress proteins, are considered to play a general role in protection
      from cellular injury. Exposure to UVA (320-400 nm) following application of 8
      methoxypsoralen (8-MOP), termed PUVA is commonly used in the field of
      dermatology. In order to understand the induction of HSP in PUVA-treated human
      skin, indirect immunofluorescence using a monoclonal antibody specific for the 72
      kDa HSP (HSP 72) was carried out in organ-cultured normal human skin that was
      treated with PUVA. When the organ-cultured skin was treated at 37 degrees for 1 h
      with 8-MOP at a final concentration of 10 or 100 micrograms/mL and exposed to UVA
      (51.3 kJ/m2), nuclear immunofluorescence of HSP 72 was detected in the epidermal
      cells 12 h after UVA irradiation. In contrast, the induction of HSP 72 was not
      detected either by UVA irradiation or 8-MOP treatment. These results suggest that
      PUVA treatment is one of the stressors for human skin, and DNA damage caused by
      PUVA induces HSP 72.

PMID- 8310001
TI  - A garlic extract protects from ultraviolet B (280-320 nm) radiation-induced
      suppression of contact hypersensitivity.
AB  - Lyophilized aged garlic extract has been incorporated at concentrations of 0.1%,
      1% and 4% by weight into semipurified powdered diets and fed to hairless mice.
      Under moderate UVB exposure conditions resulting in 58% suppression of the
      systemic contact hypersensitivity response in control-fed mice, a dose-responsive
      protection was observed in the garlic-fed mice; contact hypersensitivity in the
      UVB-exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB
      exposure was replaced by topical application of one of a series of lotions
      containing increasing concentrations of cis-urocanic acid, a dose-responsive
      suppression of contact hypersensitivity was demonstrated in control-fed mice
      (urocanic acid at 25, 50, 100 and 200 micrograms per mouse resulting in 22-46%
      suppression). Mice fed a diet containing 1% aged garlic extract were partially
      protected from cis-urocanic acid-induced suppression of contact hypersensitivity,
      with greater protection from the lower concentrations of urocanic acid. Mice fed
      a diet containing 4% aged garlic extract were protected from all concentrations
      of urocanic acid. The results indicate that aged garlic extract contains
      ingredient(s) that protect from UVB-induced suppression of contact
      hypersensitivity and suggest that the mechanism of protection is by antagonism of
      the cis-urocanic acid mediation of this form of immunosuppression.

PMID- 8310002
TI  - Antiviral activity of gilvocarcin V plus UVA radiation.
AB  - Gilvocarcin V (GV), a coumarin, is a nucleic acid photosensitizer that is
      phototoxic to bacteria and mammalian cells at picomolar levels in the presence of
      near-UV radiation (UVA). We evaluated the effectiveness of GV plus UVA for
      inactivation of several viruses, including herpes simplex virus, type 1 (HSV) and
      the bacterial viruses phi X174, T7, PRD1 and phi 6. Some inactivation of the
      bacterial viruses was observed with UVA radiation alone (4-50% survival at 26
      kJ/m2). Additional photosensitized inactivation was observed only with T7 and phi
      6 at 2.0 microM GV. On the other hand, HSV was photoinactivated with
      concentrations of GV three orders of magnitude lower (1.0 nM). Similar to the
      case with UV (254 nm) inactivation, the GV-UVA survival curve for HSV indicated
      multicomponent inactivation kinetics, which could not be explained by
      photobleaching of GV. The wide range of photosensitivities of these viruses to GV
      cannot be adequately explained by models based only on viral nucleic acid content
      or presence of lipid envelopes.

PMID- 8310003
TI  - Modulation of 8-methoxypsoralen-DNA photoadduct formation by cell
      differentiation, mitogenic stimulation and phorbol ester exposure in murine T
      lymphocytes.
AB  - The effects of cell differentiation and mitogen and phorbol ester stimulation on
      the formation of 8-methoxypsoralen (8-MOP)-DNA photoadducts in murine T
      lymphocytes were examined using 3H-8-MOP. While there were no significant
      differences in 8-MOP photoadduct formation among BALB/c thymocytes, splenocytes,
      splenic T cells and MRL/lpr lymph node cells, BALB/c bone marrow cells showed
      fewer photoadducts than did the lymphocytes. This suggested that proliferating
      progenitor cells may be resistant to 8-MOP photoadduct formation. Incubation of
      purified splenic T cells with lectin mitogens for 2 h or with phorbol 12
      myristate 13-acetate (PMA) for 2-43 h resulted in reduction of 8-MOP photoadduct
      formation in the DNA, whereas 64 h cultivation with these agents augmented the
      photoadduct formation. The reduction of photoadduct formation induced by
      phytohemagglutinin was restored by the further addition of a protein kinase C
      (PKC) inhibitor, H-7, to the culture. Thus, it is assumed that the reduction of
      adduct formation evoked by mitogens and PMA is mediated in part by the activation
      of PKC in the cells. On the other hand, the augmentation of the adduct formation
      induced by the longer-period cultures with mitogens and PMA appeared to be caused
      by down-regulation of PKC. The present study showed that the stimulatory signals
      in which PKC is presumably involved affect the ability of cells to form 8-MOP-DNA
      photoadducts.

PMID- 8310004
TI  - Comparative effect of UVA and UVB on cultured rabbit lens.
AB  - Effects on lens physiology of UVB and UVA used separately and sequentially were
      investigated using 4 week old rabbit lenses in organ culture. Narrowband UVB at
      0.3 J/cm2 = joules/lens (1 h exposure) has little effect on sodium and calcium
      concentrations in the lens interior or transparency of lenses subsequently
      cultured for 20 h after a 1 h exposure. With an incident energy of 3 J/cm2 of
      broadband UVB (295-330 nm), lenses become opaque and slightly swollen with
      significant ion imbalances during culture over a 1 day period. In contrast,
      lenses exposed to approximately 6-24 J/cm2 of UVA (330-400 nm) remain transparent
      after 1 day of culture. Extended culture up to 4 days reveals no signs of
      opacification. Ion homeostasis and normal lens hydration are also maintained in
      UVA-irradiated lenses. The presence of 95% oxygen during UVA irradiation is also
      without effect. Broadband UVA irradiation is damaging, however, if lenses are
      first exposed to subthreshold doses of narrowband UVB (307 +/- 5 nm) irradiation,
      viz. 0.3 J/cm2. Thus, sequential UVB/UVA irradiation at subthreshold doses causes
      impaired active cation transport and accumulation of sodium and calcium
      accompanying lens opacification.

PMID- 8310005
TI  - Photoreactivation in a phrB mutant of Escherichia coli K-12: evidence for the
      role of a second protein in photorepair.
AB  - In Escherichia coli, the light-dependent repair of pyrimidine dimers in UV
      irradiated DNA is now accepted as being due to enzymatic photoreactivation (PR)
      by a 50 kDa enzyme, photolyase (EC 4.1.99.3). The gene for this enzyme has been
      mapped at 16.2 min and designated phr. This gene was earlier described as phrB,
      another locus phrA having been proposed in association with PR. The relevance of
      the putative phrA gene has now been placed in doubt. The recent report of the
      discovery of a photoreactivating enzyme in Drosophila melanogaster, which
      specifically repairs pyrimidine (6-4) pyrimidone photoproducts ([6-4]
      photoproducts), and that E. coli does possess a protein with specific affinity
      for the (6-4) photoproduct, has cast new light on the prospective role of phrA in
      PR. We have determined the nucleotide sequence of the putative phrA gene, which
      suggests it codes for a protein of 38 kDa. When the putative phrA gene was cloned
      into an expression vector and transformed into a phrA phrB mutant of E. coli, a
      level of photorepair was observed, which could correspond to repair of (6-4)
      photoproducts.

PMID- 8310006
TI  - Isolation of V79 fibroblast cell lines containing elevated metallothionein levels
      that have increased resistance to the cytotoxic effects of ultraviolet-A
      radiation.
AB  - Isolated clones of V79 Chinese hamster lung fibroblasts, selected for resistance
      against cadmium toxicity, were exposed to monochromatic 365 nm ultraviolet-A
      (UVA; 320 nm to visible light) radiation and examined for cell survival. All
      three of the Cd-resistant V79 clones (V79Cd) tested exhibited significant
      increases in survival after irradiation compared with control cultures similar to
      the increased survival observed in Zn acetate-induced V79 cells. Dose-modifying
      factors calculated for these survival experiments were all approximately 1.5.
      When characterized for steady-state levels of metallothionein (MT) mRNA and
      associated Cd-binding activity, all of the Cd-resistant V79Cd clones demonstrated
      elevated constitutive levels of both, implicating MT as the mechanism responsible
      for the observed cellular resistance to Cd and also to 365 nm UVA radiation.
      However, whereas levels of intracellular MT protein correlated with differences
      in survival against Cd, MT intracellular levels did not correlate well with
      protection against 365 nm UVA. Increased cell survival after exposure to 365 nm
      UVA radiation mediated by MT appeared to reach a threshold level and MT only
      provided a limited degree of protection. Since UVA radiation is known to cause
      cell death mediated through the intracellular generation of reactive oxygen
      species (ROS), these results suggest that the role of MT in ameliorating cellular
      photooxidative damage produced by UVA is by reducing intracellular ROS.

PMID- 8310007
TI  - Collagen alterations in chronically sun-damaged human skin.
AB  - The major histological characteristic of sun-damaged skin is the accumulation of
      an elastotic material that appears to replace collagen. This elastotic material
      consists primarily of elastin and histological studies suggest a large loss of
      collagen in the dermis of chronically sun-damaged skin. In this study, we examine
      the content and distribution of collagen and procollagen in sun-damaged human
      skin. The total collagen content of sun-damaged skin was 20% less than nonsolar
      exposed skin (524 micrograms collagen per mg total protein in sun-damaged skin
      and 667 micrograms collagen per mg total protein in nonsolar-exposed skin). In
      addition, there was a 40% decrease in the content of intact amino propeptide
      moiety of type III procollagen in sun-damaged skin (0.68 U per 50 mg wet weight)
      as compared to nonsolar-exposed skin (1.12 U per 50 mg wet weight). The data
      suggest that this change in collagen content is due to increased degradation. The
      distribution of collagen in sun-damaged skin was examined by indirect
      immunofluorescence. Mild digestion of sun-damaged skin with elastase removed the
      elastin and revealed the presence of collagen in the elastotic material.
      Therefore, the elastin appears to mask the presence of collagen fibers in the
      dermis of sun-damaged skin.

PMID- 8310008
TI  - Lipid-associated methylpheophorbide-a (hexyl-ether) as a photodynamic agent in
      tumor-bearing mice.
AB  - Liposomes are a potential system for more selective delivery of photosensitizers
      (PS) to tumors. Pheophorbides are one series of new PS under investigation for
      use in photodynamic therapy. The pharmacokinetics, anti-tumor response and normal
      tissue effects of methylpheophorbide-a-(hexyl-ether) (MPH) associated with
      negatively charged phospholipid vesicles composed of high and low transition
      temperature lipids were determined in mice. In some preparations
      monosialoganglioside, which is known to impart long circulation time to liposomes
      was also included. Normally water-insoluble MPH could be quantitatively
      incorporated in multilamellar liposomes up to at least 20 mol MPH/mol lipid% for
      most liposome compositions and sonicated to form clear suspensions. Evidence from
      electron microscopy and entrapment of aqueous space markers indicated that the
      particles formed by sonication were not standard liposomes. Anti-tumor responses
      to light treatment (135 J/cm2, 665 nm argon-dye laser) 24 h after MPH (0.4
      mumol/kg) administration were slightly but significantly greater (P < 0.05) for
      lipid associated MPH compared to MPH solubilized in Tween 80. There were no major
      differences in tumor uptake and tumor cell photosensitization between lipid or
      Tween 80 formulations of MPH, whereas, dependent on lipid composition and time
      after MPH administration, the doses of light required to cause occlusive vascular
      damage were increased for the lipid formulations. Pharmacokinetic studies showed
      rapid dissociation between lipids and MPH in vivo. Lipid formulations are useful
      for solubilizing MPH and may improve the therapeutic effects of this PS.

PMID- 8310009
TI  - Characterization of skeletal muscle actin labeled with the triplet probe
      erythrosin-5-iodoacetamide.
AB  - We have labeled rabbit skeletal muscle actin with the triplet probe erythrosin-5
      iodoacetamide and characterized the labeled protein. Labeling decreased the
      critical concentration and lowered the intrinsic viscosity of F-actin filaments;
      labeled filaments were motile in an in vitro motility assay but were less
      effective than unlabeled F-actin in activating myosin S1 ATPase activity. In
      unpolymerized globular actin (G-actin), both the prompt and delayed luminescence
      were red-shifted from the spectra of the free dye in solution and the
      fluorescence anisotropy of the label was high (0.356); filament formation red
      shifted all excitation and emission spectra and increased the fluorescence
      anisotropy to 0.370. The erythrosin phosphorescence decay was at least
      biexponential in G-actin with an average lifetime of 99 microseconds while in F
      actin the decay was approximately monoexponential with a lifetime of 278
      microseconds. These results suggest that the erythrosin dye was bound at the
      interface between two actin monomers along the two-start helix. The steady-state
      phosphorescence anisotropy of F-actin was 0.087 at 20 degrees C and the
      anisotropy increased to approximately 0.16 in immobilized filaments. The
      phosphorescence anisotropy was also sensitive to binding the physiological
      ligands phalloidin, cytochalasin B and tropomyosin. This study lays a firm
      foundation for the use of this triplet probe to study the large-scale molecular
      dynamics of F-actin.

PMID- 8310010
TI  - Use of potassium iodide as a chemical actinometer.
AB  - Aqueous solutions of KI were examined for use as chemical actinometers to measure
      254 nm (germicidal) radiation. Irradiation results in electron ejection from
      iodide such that aqueous electrons and iodine atoms are formed. In the presence
      of N2O, an electron scavenger, recombination of these two reactive species is
      eliminated and stoichiometric formation of triiodide occurs. The absorbance
      increase due to triiodide was followed and the quantum yield determined using
      either a radiometer or ferrioxalate actinometry to estimate the amount of energy
      absorbed by the KI solution. The quantum yield (phi) at 25 degrees C was
      determined to be 0.26 using radiometry, and 0.224-0.233 using actinometry,
      depending on the radiation conditions. The following expression was used to
      measure the incident fluence rate for 254 radiation at a given temperature T for
      irradiation over a time interval delta t (s) [formula: see text] At temperatures
      other than 25 degrees C, the temperature dependence of the quantum yield
      (0.004/degrees C) is taken into account by the term shown in the denominator.
      Because KI remains relatively blind to longer wavelengths such as those found in
      normal room light, measurements can be made in the presence of room light without
      having to work in a darkened room.

PMID- 8310011
TI  - Dynamic capillaroscopy: a minimally invasive technique for assessing photodynamic
      effects in vivo.
AB  - A noninvasive method for visualizing the microvasculature in the mouse tail is
      described, consisting of a custom-built microscope with through-lens
      illumination. The microscope is fitted with a television camera and images can be
      recorded on videotape and displayed on a television monitor. Blood vessels are
      imaged as columns of red blood cells, in which flow is clearly observed.
      Administration of photosensitizers and illumination with the standard light
      source produces no observable photodynamic effect on blood flow. The combination
      of photosensitizer and a more intense light source (either broadband light from a
      filtered mercury arc or red light from a laser) causes photodynamic cessation of
      flow within a few minutes. The magnitude of the effect is dependent on the dose
      and nature of the photosensitizer, the delay after photosensitization and the
      match between the laser light and the absorption spectra of the photosensitizers
      in the red region. We conclude that the technique yields results consistent with
      the known photodynamic effects of the photosensitizers in tumors and propose its
      use as an initial screening method in vivo, as a means of conducting
      pharmacokinetic experiments and as an assay of prolonged cutaneous
      photosensitivity.

PMID- 8310012
TI  - Cytoplasmic free calcium changes as a trigger mechanism in the response of cells
      to photosensitization.

PMID- 8310013
TI  - Photodynamic therapy.

PMID- 8310014
TI  - Modification of the stages in total reconstruction of the auricle: Part I.
      Grafting the three-dimensional costal cartilage framework for lobule-type
      microtia.
AB  - Total auricular reconstruction for microtia is dependent on the fabricated three
      dimensional costal cartilage framework, with all the auricular features and the
      skin flaps formed and utilized to cover the three-dimensional framework, in which
      extreme caution is required. Furthermore, other factors, such as contraction of
      the skin graft, use of the remnant ear cartilage in construction of the tragus,
      and the number of surgeries required, all affect the final results of total
      auricular reconstruction for microtia, especially with reference to the contour
      of the constructed ear, morphologic locations of the auricular features,
      contraction, circulatory dysfunction, resorption, etc. The grafting of the three
      dimensional framework is the first stage of a two-stage surgical method for total
      auricular reconstruction without resorting to skin grafts, free composite grafts,
      and additional surgical procedures.

PMID- 8310015
TI  - Modification of the stages in total reconstruction of the auricle: Part II.
      Grafting the three-dimensional costal cartilage framework for concha-type
      microtia.
AB  - Among the microtic disorders, those with the remnant ear, ear lobule, concha,
      acoustic meatus, tragus, and incisura intertragica are classified as concha-type
      microtia. From these characteristic factors, concha-type microtia has been
      thought to be a milder form of microtic disorder in comparison with lobule-type
      microtia. The constructed modified three-dimensional costal cartilage framework
      is grafted to the superior portion of the auricle and fixed to the inferior
      remnant cartilage of the auricle (conchal portion). This may appear to be a
      simple procedure in comparison with the other microtic disorders, but it is
      extremely difficult to fix the modified three-dimensional framework to the
      remnant auricular cartilage so that a smooth configuration is attained at the
      seam. In this paper, the modification stages for total reconstruction of the
      auricle for concha-type microtia are discussed.

PMID- 8310016
TI  - Modification of the stages in total reconstruction of the auricle: Part III.
      Grafting the three-dimensional costal cartilage framework for small concha-type
      microtia.
AB  - The characteristic features of small concha-type microtia are the existence of
      the remnant ear and lobule and a small indentation representing the concha.
      Presently, the microtic disorder known as hypoplasia of the middle third of the
      auricle has the featured characteristics of a well-developed lobule, scapha, and
      helix and the existence of a small concha. Therefore, from these clinical aspects
      and features, the major criterion for classification for this particular type of
      microtia (small concha-type microtia) is the presence of the small concha. The
      modification stages involved in total reconstruction of the auricle for small
      concha-type microtia are described and discussed in this paper.

PMID- 8310017
TI  - Modification of the stages in total reconstruction of the auricle: Part IV. Ear
      elevation for the constructed auricle.
AB  - The contour of the constructed structures of the anterior surface of the auricle
      tends to diminish after ear elevation; thus it is extremely difficult to obtain
      the proper projection of the constructed ear without destroying the contour of
      these structures. There have been numerous articles concerned with ear elevation,
      even though most methods or procedures are plagued with problems. The major
      factors concerned with ear elevation have been described and stated in a previous
      article. This paper will discuss the major modification and refinement stages
      involved in attaining the present ear elevation method.

PMID- 8310018
TI  - Relationship between the sequence of lip and palate repair and maxillary growth:
      an experimental study in beagles.
AB  - The present study was designed to evaluate the relationship between varying
      sequences of lip and palate repair and maxillary growth. To investigate this
      problem, an experimental study using beagles was conducted to assess the
      influence of three different sequences of lip and palate repair. The first
      sequence constitutes the commonly accepted approach of lip repair first, palate
      repair second. The second sequence was reversed: palate repair first, lip repair
      second. The third sequence consisted of simultaneous lip and palate repair. Using
      70 eight-week-old beagles, we tested the following hypothesis: The sequence of
      lip repair first and palate repair second is less detrimental to maxillary growth
      than the other two sequences. The animals were assigned to two control groups
      (unoperated and unrepaired animals) and three experimental groups, in which three
      different sequences of repair were executed. Upon sacrifice, 11 maxillary
      variables were measured directly from cleaned skulls and analyzed by univariate
      and multivariate techniques. The most important finding from this analysis is
      that the commonly accepted sequence of cleft lip and palate repair (lip first,
      palate second) is less detrimental to maxillary growth than repairing the palate
      first and the lip second or simultaneous closure of both defects.

PMID- 8310019
TI  - Pharyngeal flap revisions: flap elevation from a scarred posterior pharynx.
AB  - Twenty-one consecutive patients who had earlier superiorly based pharyngeal flap
      surgery and persistent velopharyngeal insufficiency were seen between 1976 and
      1991. Patients were divided into two treatment groups, depending on the results
      of videofluoroscopic and nasopharyngoscopic assessment. The first group consisted
      of 18 patients who had bilateral port insufficiency and required a complete
      reconstruction of a new superiorly based pharyngeal flap that was elevated from a
      scarred posterior pharyngeal wall. After an average follow-up of 6.2 years, 15
      patients had normal resonance, 2 patients had improvement but continued
      hypernasality, and 1 patient was hyponasal. The second group consisted of 3
      patients who had "patch" flaps to a unilateral port insufficiency.
      Postoperatively, all 3 of those patients had normal resonance. Indications for
      the decision to "redo" or patch flaps are described.

PMID- 8310020
TI  - Three-dimensional folded free-flap reconstruction of complex facial defects using
      intraoperative modeling.
AB  - Free-tissue transfer has emerged as the ideal way of reconstructing complex
      facial defects. Multifaceted free flaps are often needed, and we have developed a
      simple technique to determine both the volume of tissue required and the
      localization of the various epithelial surfaces, thereby simplifying these
      complex reconstructions. We report our experience in reconstructing 19 complex
      facial defects in which we have used an intraoperative alginate moulage that has
      provided an accurate three-dimensional model of the defect, helping to determine
      the volume of the flap required. The reconstruction was further simplified by
      converting this three-dimensional model into a two-dimensional pattern by
      wrapping the model with a piece of Esmarch bandage, thereby determining the
      locations and sizes of the epithelial surfaces. The pattern was then transferred
      to the donor site and the flap de-epithelialized and thinned in situ with
      complete confidence that the tissue was "tailor-made" for the defect.

PMID- 8310021
TI  - Fibula osteoseptocutaneous flap for reconstruction of composite mandibular
      defects.
AB  - The fibula osteoseptocutaneous flap is a versatile method for reconstruction of
      composite-tissue defects of the mandible. The vascularized fibula can be
      osteotomized to permit contouring of any mandibular defect. The skin flap is
      reliable and can be used to resurface intraoral, extraoral, or both intraoral and
      extraoral defects. Twenty-seven fibula osteoseptocutaneous flaps were used for
      composite mandibular reconstructions in 25 patients. All the defects were
      reconstructed primarily following resection of oral cancers (23), excision of
      radiation-induced osteonecrotic lesions (2), excision of a chronic osteomyelitic
      lesion (1), or postinfective mandibular hypoplasia (1). The mandibular defects
      were between 6 and 14 cm in length. The number of fibular osteotomy sites ranged
      from one to three. All patients had associated soft-tissue losses. Six of the
      reconstructions had only oral lining defects, and 1 had only an external facial
      defect, while 18 had both lining and skin defects. Five patients used the skin
      portion of the fibula osteoseptocutaneous flaps for both oral lining and external
      facial reconstruction, while 13 patients required a second simultaneous free skin
      or musculocutaneous flap because of the size of the defects. Four of these flaps
      used the distal runoff of the peroneal pedicles as the recipient vessels. There
      was one total flap failure (96.3 percent success). There were no instances of
      isolated partial or complete skin necrosis. All osteotomy sites healed primarily.
      The contour of the mandibles was good to excellent.

PMID- 8310022
TI  - Effect of a bioresorbable film on regeneration of cranial bone.
AB  - Regeneration of cranial bone is usually accomplished with autografts, banked
      bone, or both. The effect also may be obtained by using a properly engineered
      alloplastic barrier. Our group assessed histomorphometrically the capacity of a
      bioresorbable film to promote repair of cranial bone in critical-sized defects in
      50 rabbits divided over four time periods (4, 8, 16, and 24 weeks). A single
      circular defect 15 mm in diameter was prepared in each rabbit and either covered
      with films of polylactic acid (21 mm in diameter, 150 microns thick) durally and
      pericranially or left untreated. Only after 24 weeks was there a significant
      difference (p < or = 0.05) between defects covered with polylactic acid films and
      those untreated. We conclude that after shorter periods, regardless of covering,
      prolapse of soft tissue into defects prevented osseous regeneration. We speculate
      that at 24 weeks, defects treated with films generated new bone as a result of
      changes in the local milieu conducive to osteoblastic expression.

PMID- 8310023
TI  - Treatment of traumatic tattoos by Q-switched ruby laser.
AB  - The Q-switched ruby laser is currently used in the treatment of amateur and
      professional decorative tattoos. The present study documents the clinical
      management and follow-up of 12 subjects with traumatic tattoos treated with the Q
      switched ruby laser. The results of this study indicate that an excellent
      clinical outcome can be achieved with substantial removal of the targeted foreign
      pigmented matter while potential adverse effects are significantly reduced.
      Hypopigmentation, which occurred in four patients (33.3 percent), was temporary
      and resolved spontaneously in all subjects within 6 months of laser exposure.
      There was no hypertrophic scarring, atrophy, or induration seen in any of the
      subjects treated with the Q-switched ruby laser.

PMID- 8310024
TI  - Muscle flaps in irradiated wounds: an account of 100 consecutive cases.
AB  - Radiation-related wounds challenge surgeons in all disciplines of surgery. Wound
      healing complications are commonplace, and solutions for reconstruction are
      limited. Muscle and musculocutaneous flaps have improved this situation. We ask
      the question, Does previous radiation of the muscle to be transposed affect the
      outcome? One hundred consecutive previously irradiated wounds closed with muscle
      or musculocutaneous flaps composed the group under consideration. These 100
      patients had 151 muscles transposed. The overall complication rate for muscle
      transposition to close a radiated wound was 25 percent. Of the 100 patients who
      received radiation, 43 patients had the muscle transposed for wound closure from
      the primary field of radiation. Fifty-seven patients were closed with
      nonirradiated muscle. When the transposed muscle had been radiated, the
      complication rate was 32 percent; in 14 percent, the entire muscle died,
      requiring total removal and a second tissue transposition from a nonirradiated
      source to achieve closure. The subgroup using nonirradiated muscle had a
      complication rate of 19.3 percent; no patient in this group had complete flap
      death requiring a second tissue transposition. Two postoperative deaths, one in
      each group, unrelated to the operative procedure were recorded. We feel that
      nonirradiated muscle is the best choice for closure of a radiated wound, if
      possible.

PMID- 8310025
TI  - The "split" gluteus maximus musculocutaneous flap.
AB  - The "split" gluteus musculocutaneous flap is a useful flap for perineal and
      ischial reconstruction. The flap uses the superficial 1 to 2 cm of the gluteus
      muscle, supplied by proximal parasacral perforators. It can be raised simply,
      quickly, and with minimal blood loss. Importantly, the deep muscle is left in
      place and remains innervated and well-vascularized. Deep structures are
      protected, and other flap options are preserved. Anatomic findings based on 16
      cadaver dissections (8 cadavers with bilateral dissections) are presented.
      Representative case reports and our experience with 18 consecutive cases in 17
      patients are presented.

PMID- 8310026
TI  - Cutaneous expansion using enforced position in the treatment of large skin
      defects.
AB  - This paper presents a new method of reconstruction of a large skin defect, e.g.,
      following excision of a giant pigmented nevus. By taking advantage of the
      flexibility of the joints and the extensibility of skin in the children, the
      large defects were closed in one stage by an enforced position that allows an
      easy closure of the wound. The scar was protected against stretching for 6 weeks
      to obtain sufficient strength. Later, free movements across the joints were
      permitted to allow gradual tension to the skin surrounding the scar. The final
      result is a permanent gain of the tissue replacing the defect.

PMID- 8310027
TI  - Microsurgical thumb reconstruction with toe transfer: selection of various
      techniques.
AB  - Microsurgical toe transfer is an established method for reconstruction of missing
      thumbs. However, there is little agreement on which of the various techniques
      represents the ideal transfer. Basically, selection of technique requires
      balancing the patient's functional needs, appearance of the reconstructed thumb,
      and donor-site cosmesis. Based on our experience with 103 toe-to-thumb transfers
      performed over the past 9 years, this paper attempts to provide guidelines for
      appropriate selection among the four most commonly employed toe transfer
      techniques (e.g., second toe, total great toe, great toe wrap-around, trimmed
      great toe) so that optimal results and patient's acceptance can both be achieved.

PMID- 8310028
TI  - Sculpturing the neoclitoris in vaginoplasty for male-to-female transsexuals.
AB  - One of the goals of vaginoplasty for transsexuals is the construction of an
      aesthetically appealing female perineum. Cosmetic considerations imply the
      creation of a clitoris-like structure ventral to the urethral orifice. A review
      of the scarce references on neoclitoroplasty in the literature on vaginoplasty is
      given. In our hospital, the neoclitoris is usually sculptured to its final
      appearance during the actual vaginoplasty, employing a free composite graft of
      the tip of the penile glans to cover the shortened dorsal neurovascular bundle.
      From the review of the literature and from our experience one may conclude that
      our technique presents hardly any complications and leads to acceptable results,
      both functionally and cosmetically. We consider transpositioning of the glans on
      its long dorsal neurovascular pedicle a technique with too high a risk.

PMID- 8310029
TI  - Venous ischemia in skin flaps: microcirculatory intravascular thrombosis.
AB  - Although endothelial cell injury and microcirculatory intravascular clotting have
      been implicated in the pathophysiology of skin-flap failure and various
      hematologically active drugs have been used to improve flap survival, the basic
      underlying pathophysiology has not been documented previously. In this study of
      venous ischemia in pig flaps, we focus on the accumulation and distribution of
      platelets and fibrinogen in the flap, on the morphologic changes in the flap
      microcirculation, and on changes in various coagulation factors in the venous
      effluent from the flap. Bilateral buttock skin flaps and latissimus dorsi
      myocutaneous flaps were designed and elevated on 12 pigs. All flaps had a primary
      ischemic insult (clamp application to the vascular pedicle) of 2 hours, followed
      by 2 hours of reperfusion, and then one side was subjected to a 6-hour period of
      secondary venous ischemia (clamp application to the dominant flap vein). In six
      animals, radioactively labeled autologous platelets and human fibrinogen were
      injected intravenously half an hour before termination of secondary venous
      ischemia. Flaps were weighed and counted for radioactivity. Flap biopsies and the
      buffy coat of venous effluent were processed for electron microscopy. In the
      other six animals, venous effluent was collected before secondary ischemia, upon
      immediate reperfusion, and at 4 and 8 hours after termination of secondary
      ischemia. Venous plasma levels of fibrinogen, von Willebrand factor, and
      antithrombin III were measured. Platelet and fibrinogen accumulation was
      increased in flaps with venous stasis when compared with control flaps at both
      time intervals studied; a twofold increase was seen prior to reperfusion, and a
      threefold increase was seen following 4 hours of reperfusion. Venous effluent
      could not be collected from buttock skin flaps because of slow reflow and
      clotting in the collecting system. In comparing the venous effluent of control
      flaps with that of venous ischemic latissimus dorsi flaps, hematocrit was
      significantly elevated. Blood samples collected for analysis of fibrinogen,
      antithrombin III, and von Willebrand factor could not be analyzed because of
      postcollection clotting. Electron microscopy showed extravasation of red blood
      cells and activated platelets, fibrin, and red blood cells in distended and
      partly disrupted capillaries. The venous ischemia reperfusion injury is
      associated with thrombosis in the microcirculation and alterations in consumption
      of coagulation factors. This study gives physiologic support for potential
      beneficial effects of treatment modalities that aim at counteracting the
      different components of thrombus formation.

PMID- 8310030
TI  - Arterial ischemia in skin flaps: microcirculatory intravascular thrombosis.
AB  - Although endothelial cell injury and microcirculatory intravascular thrombosis
      have been implicated in the pathophysiology of skin-flap failure, the basic
      underlying pathophysiology has not been documented previously. This study focuses
      on the morphologic changes and the alteration in platelet, fibrinogen,
      antithrombin III, and von Willebrand factor levels in flaps injured by arterial
      ischemia and reperfusion. A thrombogenic arterial anastomosis model is compared
      with simple arterial clamping as methods to achieve flap ischemia. Bilateral
      buttock skin flaps and latissimus dorsi island flaps were elevated in 12 pigs.
      All flaps had a primary ischemic insult of 2 hours' duration by simple clamp
      application. During this interval, a thrombus-generating, microvascular
      anastomosis was prepared, and during a 2-hour period of reperfusion, laser
      Doppler and transiluminator monitoring of the vascular pedicle allowed
      documentation of embolic events from the thrombus-generating anastomosis. In
      group 1 (n = 6), the flaps were then subjected to 7 (buttock skin) and 5
      (latissimus dorsi) hours of complete arterial ischemia by clamping. During the
      secondary ischemic period, the poor microanastomosis was resected and repaired.
      Radioactively labeled autologous platelets (111In) and human fibrinogen (125I)
      were injected intravenously half an hour before secondary reperfusion. After 4
      hours of reperfusion, flap biopsies and venous effluent were collected and
      prepared for electron microscopic analysis. The flaps and control tissue were
      harvested and the radioactivity was counted. In group 2 (n = 6), flaps were
      subjected to 6 hours of secondary ischemia by using the same technique as in
      group 1. Central venous and flap venous blood was sampled at baseline as well as
      upon immediate secondary reperfusion and after 4 and 8 hours of reperfusion. The
      hematocrit, platelet count, fibrinogen, antithrombin III, and von Willebrand
      factor levels were determined for these intervals. Platelets and fibrinogen
      accumulated significantly in buttock skin flaps and in the latissimus dorsi skin
      and muscle components as compared with similar control tissue (p < 0.05). There
      was no significant difference in platelet or fibrinogen accumulation after
      comparing the two ischemic models. Electron microscopic studies showed occluded
      capillaries with activated platelets in the flaps. Control tissue showed very
      little capillary occlusion. Platelet count was significantly decreased both in
      central venous (p < 0.05) and in adventitial infolding flap venous blood (p <
      0.025) during immediate reperfusion as compared with baseline. These findings
      confirm that microcirculatory intravascular thrombosis is implicated in skin-flap
      ischemia-reperfusion injury. This study provides physiologic support for
      treatment modalities aimed at counteracting the various components in the
      coagulation pathways responsible for thrombus formation.

PMID- 8310031
TI  - Upchurch Lecture. Rocky Balboa, Lenny Skutnik, and Alfred Blalock.

PMID- 8310032
TI  - Continuing medical education that continues.

PMID- 8310033
TI  - The computer and truth.

PMID- 8310034
TI  - Rupture of abdominal fascial fusion lines: an unusual complication of rectus
      abdominis flap.
AB  - Two cases of rectus abdominis muscle flaps complicated by disruption of the
      abdominal wall due to avulsion of the anterior rectus sheath from adjacent fascia
      are reported. Abnormal transmission of intraabdominal pressure is suggested as
      the cause. A polyglactin mesh patch for the prevention of abdominal disruption is
      described.

PMID- 8310035
TI  - Chylous fistula: an unusual occurrence after mastectomy with immediate breast
      reconstruction.
AB  - Postoperative lymphatic complications of mastectomy and immediate reconstruction
      are well documented, consisting predominantly of lymphorrhea, lymphocele, and
      chronic lymphoedema. Chylous fistula is a hitherto undescribed entity
      complicating breast surgery. It was managed successfully by cessation of oral
      intake and the use of intravenous fluids, as is recommended in the treatment of
      chylous fistulas occurring elsewhere in the body. Although these are exceedingly
      rare, all plastic surgeons doing breast reconstruction should be aware of chylous
      fistulas and their treatment.

PMID- 8310036
TI  - Ruben's fat pad for breast reconstruction: a peri-iliac soft-tissue free flap.
AB  - We present a single patient with a successful breast reconstruction using the
      peri-iliac fat pad as a free flap based on the deep circumflex iliac artery and
      vein. Although the follow-up is short, in this patient the donor site has been
      acceptable, and we believe that this flap will have a place in the selection of
      donor sites for autogenous tissue breast reconstruction.

PMID- 8310037
TI  - Temporary ectopic implantation of an amputated penis.
AB  - A case of temporary ectopic implantation of an amputated penis to the forearm
      followed by subsequent return to its anatomic position is reported. The penis was
      amputated by a riding lawnmower, and massive contamination of the perineum and an
      extensive hematoma precluded immediate replantation. The penile vessels were
      attached to the radial artery and venae comitantes on the forearm, where it
      survived completely. After 4 weeks, the edema and hematoma of the perineum had
      resolved, and the penis was returned to its anatomic position by microsurgical
      technique. Arteries, veins, and nerves were repaired. The penis survived in its
      entirety. Return of sensation has been excellent. A urethrocutaneous fistula
      developed that required secondary closure with local flaps. Temporary ectopic
      replantation of the penis is a useful salvage procedure when the perineum is
      heavily contaminated or too extensively damaged for immediate replantation.

PMID- 8310038
TI  - The inframammary midline triangle in reduction mammaplasty: the renewal of an old
      idea.
AB  - The junction between the inframammary and vertical suture lines after reduction
      mammaplasty is a weak point well known to plastic surgeons. This junction is
      prone to either necrosis or disruption, or both, in some cases. A small triangle
      of skin left in that location may prevent this problem. This is done routinely in
      all the cases of McKissock reduction mammaplasty, but it could be employed in any
      other techniques as well. The cosmetic appearance is good. The method, which is
      not new and has been used in the past, has been found very helpful and is
      described here along with its advantages.

PMID- 8310039
TI  - The use of Mitek anchors to secure mesh in abdominal wall reconstruction.
AB  - Abdominal wall complications of TRAM flap breast reconstruction are well
      described. Synthetic mesh abdominal reinforcement is believed to decrease the
      incidence of these complications. An innovative technique with commonly available
      suture anchors has been used in a case of recurrent abdominal laxity after a TRAM
      flap. Osseous fixation of synthetic mesh with the Mitek GII suture anchor will
      undoubtedly be used more widely in abdominal wall reconstruction.

PMID- 8310040
TI  - Plastic surgery in the cinema, 1917-1993.

PMID- 8310041
TI  - Incidence of cleft lip and palate in beagles.

PMID- 8310042
TI  - Metastatic basal cell carcinoma.

PMID- 8310043
TI  - The blood supply of the posterior tibial perforator-based flap.

PMID- 8310044
TI  - Treatment of TMJ ankylosis.

PMID- 8310045
TI  - Costochondral graft.

PMID- 8310046
TI  - High CO2 concentration alleviates the block in photosynthetic electron transport
      in an ndhB-inactivated mutant of Synechococcus sp. PCC 7942.
AB  - The high-concentration CO2-requiring mutant N5 of Synechococcus sp. PCC 7942 was
      obtained by the insertion of a kanamycin-resistant gene at the EcoRI site, 12.4
      kb upstream of rbc. The mutant is unable to accumulate inorganic carbon
      internally and exhibits very low apparent photosynthetic affinity for inorganic
      carbon but a photosynthetic Vmax similar to that of the wild type. Sequence and
      northern analyses showed that the insertion inactivated a gene highly homologous
      to ndhB, encoding subunit II of NADH dehydrogenase in Synechocystis sp. PCC 6803
      (T. Ogawa [1991] Proc Natl Acad Sci USA 88: 4275-4279). When the mutant and the
      wild-type cells were exposed to 5% CO2 in air, their photosynthetic electron
      transfer capabilities, as revealed by fluorescence and thermoluminescence
      measurements, were similar. On the other hand, a significant decrease in variable
      fluorescence was observed when the mutant (but not the wild-type) cells were
      exposed to low CO2 under continuous light. The same treatment also resulted in a
      shift (from 38-27 degrees C) in the temperature at which the maximal
      thermoluminescence emission signal was obtained in the mutant but not in the wild
      type. These results may indicate that subunit II of NADH dehydrogenase is
      essential for the functional operation of the photosynthetic electron transport
      in Synechococcus under low but not high levels of CO2. We suggest that the
      inability to accumulate inorganic carbon under air conditions stems from
      disrupture of electron transport in this mutant.

PMID- 8310047
TI  - Molecular cloning of abscisic acid-responsive mRNAs expressed during the
      induction of freezing tolerance in bromegrass (Bromus inermis Leyss) suspension
      culture.
AB  - Abscisic acid (ABA) increases the freezing tolerance of bromegrass (Bromus
      inermis Leyss) cell-suspension cultures at 23 degrees C and elicits many
      metabolic changes similar to those observed during cold acclimation. Induction
      and maintenance of freezing tolerance by ABA is accompanied by the expression of
      novel polypeptides and translatable RNAs. The objective of this study was to
      isolate and characterize ABA-responsive cDNAs associated with ABA-induced
      freezing tolerance in bromegrass cell cultures. Among the 16 ABA-responsive cDNA
      clones isolated, 9 were expressed only with ABA treatment, 7 showed increased
      transcript level, and 1 was transiently expressed. Cold responsiveness was
      determined in three clones with increased transcript levels and in the
      transiently expressed clone. Deacclimation of ABA-hardened cells was a relatively
      slow process, because all of the novel transcripts persisted for at least 7 d
      after cells were cultured in ABA-free medium. Preliminary sequencing of cDNAs has
      identified several clones that share high sequence homology with genes associated
      with sugar metabolism, osmotic stress, and protease activity. Clone pBGA61 was
      fully sequenced and tentatively identified as an NADPH-dependent aldose
      reductase. The predicted amino acid sequence of the coding region shared 92%
      similarity with that predicted for barley aldose reductase cDNA. It is proposed
      that expression of genes related to sugar metabolism and osmotic stress may be
      required for ABA-induced hardening.

PMID- 8310048
TI  - A plant receptor-like gene, the S-locus receptor kinase of Brassica oleracea L.,
      encodes a functional serine/threonine kinase.
AB  - To investigate the catalytic properties of the Brassica oleracea S-locus receptor
      kinase (SRK), we have expressed the domain that is homologous to protein kinases
      as a fusion protein in Escherichia coli. Following in vivo labeling of cultures
      with 32P-labeled inorganic phosphate, we observed phosphorylation of the fusion
      protein on serine and threonine, but not on tyrosine. In contrast, labeling was
      not observed when lysine-524, a residue conserved among all protein kinases, was
      mutated to arginine, thus confirming that SRK phosphorylation was the result of
      intrinsic serine/threonine kinase activity.

PMID- 8310049
TI  - cDNA cloning and sequence analysis of a pathogen-induced thaumatin-like protein
      from rice (Oryza sativa).

PMID- 8310050
TI  - Nucleotide sequence of a rice (Oryza sativa) prolamin storage protein gene, RP6.

PMID- 8310051
TI  - Nucleotide sequence of the tobacco (Nicotiana tabacum) anionic peroxidase gene.

PMID- 8310052
TI  - Arabidopsis DNA encoding two desiccation-responsive rd29 genes.

PMID- 8310053
TI  - Nucleotide sequence of a pea (Pisum sativum L.) beta-1,3-glucanase gene.

PMID- 8310054
TI  - Nucleotide sequence of a cDNA encoding ribosomal protein L27 from Chlamydobotrys
      stellata.

PMID- 8310055
TI  - Cloning, expression, and crystallization of jack bean (Canavalia ensiformis)
      canavalin.
AB  - Canavalin is the major storage protein of the jack bean (Canavalia ensiformis)
      and belongs to the classical vicilin fraction. A full-length cDNA for canavalin
      was generated by the polymerase chain reaction. The nucleotide sequence coding
      for canavalin and the corresponding amino acid sequence were determined and shown
      to be homologous with those of other seed storage proteins. The amino acid
      sequence contained an internal sequence duplication corresponding to the
      structural redundancy in the monomer demonstrated by crystallographic analysis.
      The coding region of the canavalin cDNA was inserted into a T7 RNA polymerase
      expression vector and used to transform Escherichia coli. A recombinant protein
      with a molecular mass of 47 kilodaltons was expressed and purified to 95%
      homogeneity. The protein exhibited the same physical, immunological, and
      biochemical properties as native jack bean canavalin. Recombinant canavalin,
      following treatment with trypsin, was crystallized in two forms. Crystals of a
      rhombohedral habit grew to 1 mm in the longest dimension and diffracted to beyond
      3-A resolution. Three-dimensional diffraction data demonstrated crystals of the
      recombinant protein to be isomorphous with crystals of the natural plant protein,
      thereby confirming the identity of their structures.

PMID- 8310056
TI  - The three-dimensional structure of canavalin from jack bean (Canavalia
      ensiformis).
AB  - The three-dimensional structure of the vicilin storage protein canavalin, from
      Canavalia ensiformis, has been determined in a hexagonal crystal by x-ray
      diffraction methods. The model has been refined at 2.6 A resolution to an R
      factor of 0.197 with acceptable geometry. Because of proteolysis, 58 of 419 amino
      acids of the canavalin polypeptide are not visible in the electron density map.
      The canavalin subunit is composed of two extremely similar structural domains
      that reflect the tandem duplication observed in the cDNA and in the amino acid
      sequence. Each domain consists of two elements, a compact, eight-stranded beta
      barrel having the "Swiss roll" topology and an extended loop containing several
      short alpha-helices. The root mean square deviation between 84 pairs of
      corresponding C alpha atoms making up the strands of the two beta-barrels in a
      subunit is 0.78 A, and for 112 pairs of structurally equivalent C alpha atoms of
      the two domains the deviation is 1.37 A. The interface between domains arises
      from the apposition of broad hydrophobic surfaces formed by side chains
      originating from one side of the beta-barrels, supplemented by at least four salt
      bridges. The interfaces between subunits in the trimer are supplied by the
      extended loop elements. These interfaces are also composed primarily of
      hydrophobic residues supplemented by six salt bridges. The canavalin subunits
      have dimensions about 40 x 40 x 86 A, and the oligomer is a disk-shaped molecule
      about 88 A in diameter with a thickness of about 40 A. The distribution of
      domains lends a high degree of pseudo-32-point group symmetry to the molecule.
      There is a large channel of 18 A diameter, lined predominantly by hydrophilic and
      charged amino acids, running through the molecule along the 3-fold axis. The
      majority of residues conserved between domains and among vicilins occur at the
      interface between subunits but appear otherwise arbitrarily distributed within
      the subunit, although predominantly on its exterior.

PMID- 8310057
TI  - An osmotic stress protein of cyanobacteria is immunologically related to plant
      dehydrins.
AB  - Dehydrins are a family of desiccation proteins that were identified originally in
      plants (T.J. Close, A.A. Kortt, P.M. Chandler [1989] Plant Mol Biol 13: 95-108;
      G. Galau, T.J. Close [1992] Plant Physiol 98: 1523-1525). Dehydrins are
      characterized by the consensus amino acid sequence domain EKKGIMDKIKEKLPG found
      at or near the carboxy terminus; the core of this domain (KIKEKLPG) may be
      repeated from one to many times within the complete polypeptide. Dehydrins
      generally accumulate in plants in response to dehydration stress, regardless of
      whether the stimulus is evaporation, chilling, or a decrease in external osmotic
      potential. Polyclonal antibodies highly specific to the consensus carboxy
      terminus of plant dehydrins were used to search for dehydrins in cyanobacteria,
      many of which are known to survive desiccation. A 40-kD osmotic-stress-induced
      protein was identified in Anabaena sp. strain PCC 7120. The 40-kD protein was
      usually not detected in logarithmic cultures and was induced by shifting the
      growth medium to higher solute concentrations. Several solutes have inductive
      effects, including sucrose, sorbitol, and polyethylene glycol (PEG). Measurements
      of osmotic potential suggest that a shift of -0.5 MPa (sucrose and PEG) or -1.2
      MPa (sorbitol) is sufficient to induce synthesis of the 40-kD protein. Glycerol,
      which is highly permeable, was not an inducer at -1.2 MPa (0.5 M), nor was the
      plant hormone abscisic acid. Induction appears to be evoked by a shift in osmotic
      potential approximately equal in absolute magnitude to the expected turgor
      pressure of bacterial cells in logarithmic phase growth. A dehydrin-like
      polypeptide was also identified among osmotically induced proteins from two other
      filamentous, heterocyst-forming cyano-bacteria. A 40-kD protein was observed in
      Calothrix sp. strain PCC 7601, and in Nostoc sp. strain Mac-R2, an osmotic
      induced doublet at 39 and 40 kD was observed. From these data, it appears that
      cyanobacteria produce a dehydrin-like protein under osmotic stress.

PMID- 8310058
TI  - Arabidopsis rbcS genes are differentially regulated by light.
AB  - Individual members of the Arabidopsis thaliana ribulose-1,5-bisphosphate
      carboxylase/oxygenase small subunit (rbcS) gene family are differentially
      regulated by light of different qualities. In 10-d-old etiolated seedlings, the
      expression of only three of the four genes is under inductive phytochrome
      control. rbcS mRNA levels reach a maximum (3- to 5-fold higher than the dark
      level) about 6 h after a red light pulse, but the rate of decay differs among the
      genes. Moreover, rbcS 2B requires a higher fluence for induction. At early stages
      of development, rbcS 1A, 2B, and 3B are highly expressed in the dark and cannot
      be further induced by red light, indicating a developmental component in the
      overall regulatory mechanism. Continuous light experiments indicate that high
      irradiance responses may play a role in the induction of at least three of the
      four rbcS genes. Under conditions of phytochrome saturation, rbcS 1A is
      insensitive to blue light pulses, whereas among the three B locus genes, at least
      rbcS 3B appears to respond to a blue-light photoreceptor. These results add to
      the data suggesting that individual members of rbcS gene families in higher
      plants may be subject to a variety of differing regulatory mechanisms.

PMID- 8310059
TI  - Isolation and characterization of a cDNA clone for plant nuclear antigen 21D7
      associated with cell division.
AB  - A cDNA clone was isolated from a carrot (Daucus carota L.) cDNA expression
      library using monoclonal antibody 21D7, which recognizes a nuclear antigen
      associated with cell division in plant cells. To show that the isolated cDNA
      encodes the 21D7 antigen, a polyclonal antiserum was raised against a recombinant
      fusion protein specified by the cDNA. Both the polyclonal antiserum and the
      monoclonal antibody 21D7 recognized the same plant protein on immunoblots, in
      immunoprecipitation experiments, and in peptide mapping. Analysis of the cDNA
      revealed that the deduced amino acid sequence has 45% identity to the predicted
      sequence of the mouse transplantation antigen P91A from mutant tumor cells that
      is responsible for the immune rejection of the corresponding cell clone in a
      syngeneic mouse. The expression of the plant cDNA at the mRNA level was highly
      correlated with cell proliferation. In suspension cultures of Catharanthus roseus
      (L.) G Don. cells, the highest level of expression was observed during the
      midlogarithmic phase of growth. When auxin was added to stimulate cell division
      of auxin-starved cells arrested in the G1 phase, transcription was immediately
      enhanced, and the level of expression remained high throughout the G1 and S
      phases and dropped dramatically at the end of DNA replication.

PMID- 8310061
TI  - Posttranslational processing of a new class of hydroxyproline-containing
      proteins. Prolyl hydroxylation and C-terminal cleavage of tobacco (Nicotiana
      tabacum) vacuolar chitinase.
AB  - The fungicidal class I chitinases (EC 3.2.1.14) are believed to be important in
      defending plants against microbial pathogens. The vacuolar isoforms of tobacco
      (Nicotiana tabacum), chitinases A and B, are the first examples of a new type of
      hydroxyproline-containing protein with intracellular location, enzymic activity,
      and a small number of hydroxyprolyl residues restricted to a single, short
      peptide sequence. We have investigated the posttranslational processing and
      intracellular transport of transgene-encoded chitinase A in callus cultures of
      Nicotiana tabacum L. cv Havana 425 and leaves of Nicotiana sylvestris Spegazzini
      and Comes. Pulse-chase experiments and cell fractionation show that chitinase A
      is processed in two distinct steps. In the first step, the nascent protein
      undergoes an increase in apparent M(r) of approximately 1500 detected by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. Experiments with the
      inhibitor of prolyl hydroxylation, alpha,alpha'-dipyridyl, and pulse-chase
      labeling of cells expressing recombinant forms of chitinase A indicate that the
      anomalous increase in M(r) is due to hydroxylation of prolyl residues. This step
      occurs in the endomembrane system before sorting for secretion and vacuolar
      transport and does not appear to be required for correct targeting of chitinase A
      to the vacuole. The second step is a proteolytic cleavage. Sequencing of tryptic
      peptides of the mature proteins indicates that during processing essentially all
      molecules of chitinase A and B lose a C-terminal heptapeptide, which has been
      shown to be a vacuolar targeting signal. This appears to occur primarily in the
      endomembrane system late in intracellular transport. A model for the
      posttranslational modification of chitinase A is proposed.

PMID- 8310060
TI  - Analysis of genes negatively regulated by phytochrome action in Lemna gibba and
      identification of a promoter region required for phytochrome responsiveness.
AB  - As a step to understanding how the photoreceptor phytochrome acts to change the
      transcription of specific nuclear genes in Lemna gibba, we wish to compare
      promoter elements involved in negative regulation by phytochrome with those
      involved in positive regulation. We have isolated three genes negatively
      regulated by phytochrome, designated NR (negatively phytochrome regulated) genes
      (P.A. Okubara, E.M. Tobin [1991] Plant Physiol 96:1237-1245), and we have now
      sequenced two of these. The promoters of both contain some sequence motifs that
      are identical with motifs from other genes. We used a transient assay in L. gibba
      to demonstrate that approximately 1.7 kb pairs of the NPR1 promoter and 1.1 kb
      pairs of the NPR2 promoter could confer negative phytochrome regulation to a
      luciferase reporter gene. Deletion analysis of the NPR2 promoter showed that
      sequences between -208 and -82 from the transcription start were necessary for
      negative phytochrome regulation. However, this region was not sufficient to
      confer negative regulation by phytochrome to another promoter. Additionally, we
      noted that this region showed no similarity to a region identified as important
      for the negative regulation of the oat phyA promoter (W.B. Bruce, X.-W. Deng,
      P.H. Quail [1991] EMBO J 10:3015-3024), but it does contain a sequence element
      found in several other kinds of genes, including ones positively regulated by
      phytochrome. The deduced amino acid sequences of NPR1 and NPR2 were found to
      share similarities with many abscisic acid-induced or seed-abundant proteins.
      Thus, these genes, like other phytochrome-regulated genes, might respond to
      multiple regulatory signals.

PMID- 8310062
TI  - cDNA sequence, expression, and transcript stability of a cold acclimation
      specific gene, cas18, of alfalfa (Medicago falcata) cells.
AB  - The nucleotide sequence of a full-length cDNA, the deduced amino acid sequence,
      and the regulation of expression of a cold acclimation-specific gene, cas18, in
      cell suspension cultures of a freezing-tolerant cultivar of alfalfa (Medicago
      falcata cv Anik) have been determined. The deduced polypeptide, CAS18, is
      relatively small (17.6 kD), is highly hydrophilic, is rich in glycine and
      threonine, and contains two distinctive repeat elements. It exhibits homology
      with members of the LEA/RAB/dehydrin family of proteins, which accumulate in
      response to abscisic acid (ABA) or water stress. It is intriguing that cas18 is
      induced by neither ABA nor water stress. The cas18 cDNA hybridizes to three
      transcripts of 1.6, 1.4, and 1.0 kb, and the cDNA characterized here corresponds
      to the 1.0-kb transcript. The expression of this gene is about 30-fold greater in
      cold-acclimated cells than in nonacclimated cells. Although the accumulation of
      transcripts during cold acclimation is relatively slow, their disappearance
      during deacclimation is dramatically rapid, becoming undetectable in less than 5
      h. Studies of nuclear run-on transcription show that cold acclimation enhances
      the transcription of this gene nearly 9-fold. The stability of cas18-detectable
      transcripts during deacclimation is considerably increased if transcription is
      inhibited with cordycepin. It therefore appears that low temperature regulates
      the expression of cas18 at both the transcriptional and posttranscriptional
      levels.

PMID- 8310063
TI  - Purification and characterization of three soluble invertases from barley
      (Hordeum vulgare L.) leaves.
AB  - Three soluble isoforms of invertase (beta-fructofuranosidase; EC 3.2.1.26) were
      purified from 7-d-old primary leaves of barley (Hordeum vulgare L.). Invertase I,
      a monomeric protein of 64 kD, was purified to apparent homogeneity as shown by
      sodium dodecylsulfate-polyacrylamide gel electrophoresis. Invertases IIA and IIB,
      multimeric proteins with molecular masses of the 116 and 155 kD, were purified
      780- and 1370-fold, respectively, but were not yet homogeneous. Extracts of
      epidermal strips of leaves contained only invertase IIB. The specific activity of
      invertase was more than 100-fold higher in the epidermis than in the mesophyll.
      All three isoforms were acidic invertases, with pH optima of around 5.0 and
      little activity in the alkaline range. Invertase I had a Km for sucrose of 8.1
      mM, and invertases IIA and IIB had much lower values of 1.0 and 1.7 mM,
      respectively. Invertase I was more than 2-fold more resistant than the other two
      invertases to the inhibitors HgCl2 and pyridoxal. All three constitutive
      invertases were found to act also as sucrose-sucrose fructosyltransferases when
      supplied with high concentrations of sucrose, forming 1-kestose as principal
      product. However, the fructosyltransferase activity of all three enzymes was
      inhibited by pyridoxal in the same way as their invertase activity. This
      characteristic clearly differentiates them from the inducible sucrose-sucrose
      fructosyltransferase of barley leaves, the activity responsible for the initial
      steps of fructan biosynthesis, which has previously been shown to be insensitive
      to pyridoxal.

PMID- 8310064
TI  - Activation of bean (Phaseolus vulgaris) alpha-amylase inhibitor requires
      proteolytic processing of the proprotein.
AB  - Seeds of the common bean (Phaseolus vulgaris) contain a plant defense protein
      that inhibits the alpha-amylases of mammals and insects. This alpha-amylase
      inhibitor (alpha AI) is synthesized as a proprotein on the endoplasmic reticulum
      and is proteolytically processed after arrival in the protein storage vacuoles to
      polypeptides of relative molecular weight (M(r)) 15,000 to 18,000. We report two
      types of evidence that proteolytic processing is linked to activation of the
      inhibitory activity. First, by surveying seed extracts of wild accessions of P.
      vulgaris and other species in the genus Phaseolus, we found that antibodies to
      alpha AI recognize large (M(r) 30,000-35,000) polypeptides as well as typical
      alpha AI processing products (M(r) 15,000-18,000). Alpha AI activity was found in
      all extracts that had the typical alpha AI processed polypeptides, but was absent
      from seed extracts that lacked such polypeptides. Second, we made a mutant alpha
      AI in which asparagine-77 is changed to aspartic acid-77. This mutation slows
      down the proteolytic processing of pro-alpha AI when the gene is expressed in
      tobacco. When pro-alpha AI was separated from mature alpha AI by gel filtration,
      pro-alpha AI was found not to have alpha-amylase inhibitory activity. We
      interpret these results to mean that formation of the active inhibitor is
      causally related to proteolytic processing of the proprotein. We suggest that the
      polypeptide cleavage removes a conformational constraint on the precursor to
      produce the biochemically active molecule.

PMID- 8310065
TI  - Effect of brefeldin A on the structure of the Golgi apparatus and on the
      synthesis and secretion of proteins and polysaccharides in sycamore maple (Acer
      pseudoplatanus) suspension-cultured cells.
AB  - Brefeldin A (BFA), a specific inhibitor of Golgi-mediated secretion in animal
      cells, has been used to study the organization of the secretory pathway and the
      function of the Golgi apparatus in plant cells. To this end, we have employed a
      combination of electron microscopical, immunocytochemical, and biochemical
      techniques to investigate the effects of this drug on the architecture of the
      Golgi apparatus as well as on the secretion of proteins and complex cell wall
      polysaccharides in sycamore maple (Acer pseudoplatanus) suspension-cultured
      cells. We have used 2.5 and 7.5 micrograms/mL of BFA, which is comparable to the
      1 to 10 micrograms/mL used in experiments with animal cells. Electron micrographs
      of high-pressure frozen and freeze-substituted cells show that although BFA
      causes swelling of the endoplasmic reticulum cisternae, unlike in animal cells,
      it does not induce the disassembly of sycamore maple Golgi stacks. Instead, BFA
      induces the formation of large clusters of Golgi stacks, an increase in the
      number of trans-like Golgi cisternae, and the accumulation in the cytoplasm of
      very dense vesicles that appear to be derived from trans Golgi cisternae. These
      vesicles contain large amounts of xyloglucan (XG), the major hemicellulosic cell
      wall polysaccharide, as shown by immunocytochemical labeling with anti-XG
      antibodies. All of these structural changes disappear within 120 min after
      removal of the drug. In vivo labeling experiments using [3H]leucine demonstrate
      that protein secretion into the culture medium, but not protein synthesis, is
      inhibited by approximately 80% in the presence of BFA. In contrast, the
      incorporation of [3H]fucose into N-linked glycoproteins, which occurs in trans
      Golgi cisternae, appears to be affected to a greater extent than the
      incorporation of [3H]xylose, which has been localized to medial Golgi cisternae.
      BFA also affects secretion of complex polysaccharides as evidenced by the
      approximate 50% drop in incorporation of [3H]xylose and [3H]fucose into cell wall
      hemicelluloses. Taken together, these findings suggest that at concentrations of
      2.5 to 7.5 mu g/mL BFA causes the following major changes in the secretory
      pathway of sycamore maple cells: (a) it inhibits the transport of secretory
      proteins to the cell surface by about 80% and of hemicelluloses by about 50%; (b)
      it changes the patterns of glycosylation of N-linked glycoproteins and
      hemicelluloses; (c) it reduces traffic between trans Golgi cisternae and
      secretory vesicles; (d) it produces a major block in the transport of XG
      containing, dense secretory vesicles to the cell surface; and (e) it induces the
      formation of large aggregates of Golgi apparatus of plant and animal cels share
      many functional and structural characteristics, the plant Golgi apparatus
      possesses properties that make its response to BFA unique.

PMID- 8310066
TI  - A calcium/calmodulin-binding serine/threonine protein kinase homologous to the
      mammalian type II calcium/calmodulin-dependent protein kinase is expressed in
      plant cells.
AB  - cDNA fragments corresponding to an apple (Malus domestica [L.] Borkh) calmodulin
      binding polypeptide have been isolated and characterized. The protein encoded by
      this messenger contains a serine/threonine protein kinase catalytic domain
      followed by a calcium/calmodulin-binding regulatory domain, both exhibiting
      significant sequence similarities to the corresponding regions of the mammalian
      calcium/calmodulin-dependent protein kinase II subunits. These results confirm a
      potential regulatory role for calmodulin in phosphorylation-mediated signal
      transduction events.

PMID- 8310067
TI  - Evidence that the putative compatible solute 5-dimethylsulfoniopentanoate is an
      extraction artifact.
AB  - A novel gas chromatography-mass spectrometry method for analyzing sulfonium
      compounds as their S-demethylated silyl derivatives has clarified the origin of 5
      dimethylsulfoniopentanoate. This compound, previously reported from flowers of
      Diplotaxis tenuifolia (L.) DC. (Cruciferae), is generated from glucoerucin during
      treatment with hot 6 N HCl. Glucoerucin is the characteristic glucosinolate of D.
      tenuifolia.

PMID- 8310068
TI  - Cauliflower mosaic virus isolate CMV-1.

PMID- 8310069
TI  - Nucleotide sequence of an Arabidopsis thaliana turgor-responsive cDNA clone
      encoding TMP-A, a transmembrane protein containing the major intrinsic protein
      motif.

PMID- 8310070
TI  - p34cdc2 protein kinase homolog from mothbean (Vigna aconitifolia).

PMID- 8310071
TI  - Nucleotide sequences of cDNAs encoding the precursors for soybean (Glycine max)
      trypsin inhibitors (Kunitz type).

PMID- 8310072
TI  - Nucleotide sequence of a Brassica napus endochitinase gene.

PMID- 8310073
TI  - Identification of a cDNA clone coding for a novel calcium-binding protein from
      potato tuber.

PMID- 8310075
TI  - Isolation and characterization of a cDNA clone encoding a small wound-inducible
      protein from Phaseolus vulgaris.

PMID- 8310074
TI  - Sequence of a tobacco (Nicotiana tabacum) gene coding for type A phytochrome.

PMID- 8310076
TI  - New cold- and drought-regulated gene from Medicago sativa.

PMID- 8310078
TI  - A fifth 2S albumin isoform is present in Arabidopsis thaliana.

PMID- 8310077
TI  - Nucleotide sequence of a stamen- and tapetum-specific gene from Lycopersicon
      esculentum.

PMID- 8310079
TI  - Joint and soft-tissue arthrocentesis.
AB  - Diagnostic arthrocentesis and therapeutic joint and soft tissue injections are
      important components in the treatment of musculoskeletal complaints for the
      primary care physician. Proper knowledge of joint architecture anatomic
      landmarks, indications, contraindications, and complications of injection will
      enable the physician to provide the patient with a maximum of benefit with a
      minimum of risk.

PMID- 8310080
TI  - Radiology of arthritis.
AB  - The radiographic evaluation of the arthritides still relies primarily on the
      plain films that are readily available to every practicing clinician. The
      radiographic examination serves primarily to confirm the clinician's diagnosis
      based on the history, clinical findings, and laboratory studies and to document
      the severity of the arthritic changes. On occasion, the radiographic studies will
      be diagnostic when other findings are equivocal and the diagnosis is in question.
      The radiographic studies, in association with the other data, should result in a
      firm diagnosis greater than 90% of the time. This review article has outlined the
      basic features of the common arthritides and hopefully will serve as a handy
      reference in office practice for the evaluation of a patient with arthritis.
      There will always be unusual or perplexing cases that may require reference to
      text books devoted exclusively to the radiology of arthritis and bone disease. Of
      course, you can always get some excellent help by consulting with your local
      radiologist.

PMID- 8310081
TI  - A pragmatic approach to cost-effective use of laboratory tests and imaging
      procedures in patients with musculoskeletal symptoms.
AB  - In this article, serologic tests and other procedures widely used to establish
      diagnoses of patients with rheumatic diseases are discussed. Musculoskeletal
      conditions are among the most common seen by physicians, and the current practice
      of including extensive laboratory tests and imaging procedures is not only
      ineffective but frequently results in misdiagnosis and inappropriate treatment.
      The approach outlined should provide treatment that is not only cost-effective
      but is directed to relief of symptoms and preservation of function, which are the
      primary goals of the patient and physician in the management of musculoskeletal
      problems. The costs in diagnosis of most patients with musculoskeletal pain often
      are considerably greater than the costs of treatment, which might be a reasonable
      consideration if expensive diagnostic studies would provide meaningful
      specificity regarding treatment. Many results, however, are misleading, for
      example, phenomena seen in at least 1% of the population, such as elevated ESR,
      rheumatoid factor titer, ANA, elevated uric acid, and Lyme Borreliosis titer, may
      be seen in individuals whose primary problem is fibromyalgia. In view of the fact
      that treatment is generally based on clinical observations, a considerable
      reduction in diagnostic studies might considerably reduce costs of patient care,
      without adversely affecting results and outcomes.

PMID- 8310082
TI  - Osteoarthritis.
AB  - Osteoarthritis is the most common form of chronic joint disease. This article
      provides an overview of the epidemiology and pathogenesis. Approaches to the
      differential diagnosis and management of multiple clinical regional
      osteoarthritis syndrome are reviewed.

PMID- 8310083
TI  - Diagnosis and treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis is a chronic, inflammatory, connective-tissue disease that
      has well-defined clinical and laboratory characteristics. The management of
      rheumatoid arthritis requires an aggressive multidisciplinary treatment combining
      both pharmacologic and nonpharmacologic measures. Using this approach, most
      patients with rheumatoid arthritis can maintain their functional capacity while
      having their pain and suffering relieved.

PMID- 8310084
TI  - Gout and pseudogout.
AB  - This article describes the clinical spectrum of gout and pseudogout and discusses
      the role of colchicine, NSAIDs, and uric acid--lowering agents in the management
      of different stages of gout. A great majority of patients with gout are now seen
      and treated by primary care physicians. Strategy for successful management of
      gout and prevention of its disabling complications are discussed also.

PMID- 8310085
TI  - Arthritis-associated syndromes.
AB  - There are a number of diseases characterized by inflammatory arthropathy that,
      although not as commonly seen as rheumatoid arthritis, often present to the
      family physician as difficult diagnostic problems. The diagnosis is frequently
      most difficult during the early course of these diseases. During recent years,
      new and altered concepts have arisen regarding both diagnostic and therapeutic
      management of this challenging group of arthropathies. This article presents a
      review of the more common arthritis-associated syndromes with emphasis on the
      differential diagnosis and medicinal therapeutics.

PMID- 8310086
TI  - Juvenile arthritis.
AB  - Juvenile arthritis encompasses a group of chronic arthritides in childhood with
      unclear etiologies. Careful clinical observation has led to categorization and
      nomenclature identifying three main subtypes of the disease, each with varying
      natural histories and prognoses. Management centers around antiinflammatory
      drugs, long-term disease-modifying agents, physical and occupational therapy,
      joint replacement, and ongoing psychosocial assessment and care. The majority of
      patients achieve reasonable control of their symptoms and are able to attain
      independent and satisfying adult lives.

PMID- 8310087
TI  - Arthritis and exercise.
AB  - Exercise is medicine. It promotes health and can be instrumental in the treatment
      of chronic disease. Current knowledge suggests that exercise carried out within
      the limits of normal joint motion and comfort does not predispose to
      osteoarthritis. In fact, normal repetitive loading to a joint is essential for
      its physiologic function. Sports that subject joints to intermittent high or
      violent impact loads may increase the risk of subsequent osteoarthritis, but well
      designed studies are lacking and this association is at best speculative. There
      is clear evidence, however, that joints with preexisting injury, particularly if
      there is biomechanical alteration, are at increased risk of developing
      osteoarthritis with repetitive loading. Finally, patients with arthritis can
      derive a number of benefits from a thoughtful and closely monitored exercise
      program.

PMID- 8310088
TI  - Geriatric issues in the diagnosis and management of patients with rheumatic
      disorders.
AB  - The musculoskeletal diseases account for the most frequent complaints among older
      persons. Rarely is it possible to provide the patient with complete symptomatic
      relief. Instead, the patient needs to be taught good health habits, good concepts
      of preventive care, the value of rehabilitation, the gains to be achieved through
      non-pharmacologic therapy, and a recognition that symptoms reflect emotional
      problems as well as diseased musculoskeletal tissue. Most important, the patient
      needs to be taught that he or she can live a full exciting life despite the
      limitations imposed by the musculoskeletal disease. Encouragement of this
      attitude and institution of any and all measures that will enhance the patient's
      ability to retain independence are the major components of ongoing care for this
      growing segment of our population.

PMID- 8310089
TI  - Dermatologic manifestations of rheumatic disorders.
AB  - Many rheumatic disorders have cutaneous lesions and sometimes skin lesions are
      the initial or most problematic manifestation of a patient's rheumatic disease.
      Many of the skin lesions encountered in these disorders are rather nonspecific.
      Other lesions, however, have characteristic and sometimes specific gross or
      histopathologic findings that often help the clinician diagnose the underlying
      rheumatic disease process. Additionally, drug-induced skin diseases are often
      encountered in patients being treated for rheumatic disease.

PMID- 8310090
TI  - Infectious arthritis.
AB  - Infectious arthritis should be suspected in any patient with a swollen joint but
      especially in children, debilitated patients, immunocompromised persons, those
      with infection elsewhere (even if on antibiotics), and those with other types of
      arthritis or a prosthetic joint. Diagnosis depends on obtaining joint fluid for
      culture and Gram stain. Initial appropriate broad spectrum antibiotics are best
      narrowed to suit the individual organism, which 2 to 6 weeks of therapy can
      eradicate. Repeated needle aspiration or surgical drainage is usually helpful in
      lessening joint damage and achieving a more rapid resolution of symptoms.

PMID- 8310091
TI  - Current nonsteroidal anti-inflammatory drug applications for rheumatic diseases.
AB  - This article reviews recent knowledge of the pharmacology of non-steroidal anti
      inflammatory drugs (NSAIDs). Changes in use and perception of safety
      considerations are discussed. Additionally, the concept that all NSAIDs are both
      anti-inflammatory and analgesic is introduced, discussing the mechanism for each
      effect. A glimpse into the future of NSAIDs is presented, including different
      formulations and the concept of enantiomers and their possible role in future
      developments.

PMID- 8310092
TI  - [The most important side effects of clozapine (Leponex) and their treatment].
AB  - The side-effect profile of Clozapine (Leponex) plays a major role both from a
      negative and a positive perspective. Prevention and management of the most
      important and most frequent side-effects, of interest in daily patient practice,
      are primordial concerns. Additionally, attention is also paid to the question
      treatment and to potential problems with medication discontinuation.

PMID- 8310093
TI  - [Indications for psychiatric consultation: a case-specific parallel survey of
      psychiatrists and treating physicians].
AB  - In a prospective study about the consultation triad (doctor-doctor-patient) 334
      of 388 consecutive psychiatric consultations at two large hospitals of Lubeck
      within 5 months have been analyzed. The psychiatric consultant and the doctor on
      duty answered questions with regard to diagnosis, treatment indication and after
      care. 162 physicians (22 psychiatric consultants and 140 physicians working in 14
      different departments) took part in the study. On one hand it turned out that
      there were specific indications for different diagnosis groups. On the other hand
      the two samples of physicians presented surprising differences with regard to
      their (case related) treatment indications and after care options. Psychiatrists
      found it less important to carry out reconsultations and the somatic orientated
      doctors emphasized more often psychodynamical orientated interventions for
      patients in contrast to the psychiatrists. Psychiatrists in contrast have been
      more sensitive for atmospheric tensions at the ward. These differences even grew
      following the amount of practice. Gerontopsychiatric patients turned out to be a
      special problem group. Doctors of both groups rarely share their opinion with
      regard to after care options.

PMID- 8310094
TI  - [Neuropsychiatric nursing in the intensive care unit as an aspect of psychiatric
      consultation].
AB  - Psychiatric training of nurses on ICUs is important, as cerebral dysfunctional
      states often show disturbances of behaviour. With two case reports of patients
      seen by our psychiatric service to an ICU, we want to demonstrate the potential
      benefits of a neuropsychiatric training for nurses. The implementation of
      psychiatric nurse clinical specialists on ICUs is suggested.

PMID- 8310095
TI  - [ERWIPA--a standardized inventory for assessment of illness-related insight in
      patients with schizophrenia].
AB  - 55 schizophrenic patients answered a 2 x 30 items questionnaire, Item analysis
      showed a low discriminative power, the initial forms differing with regard to
      degree of difficulty. Items with discriminative power over 0.30 were arranged
      into two thematically similar 13 item forms of equal difficulty. The
      questionnaires ERWIPA-A and ERWIPA-B consist of 2 x 20 items. The first item of
      each from had been answered correctly by all patients from our sample. We
      considered six additional items because future research may to different results
      as far as discriminative power is concerned. The average difficulty of both
      ERWIPA forms is equal for both the 2 x 13 items and the 2 x 20 items version.

PMID- 8310096
TI  - [Late immigrants and psychiatric disease: case report from a day care clinic].

PMID- 8310097
TI  - [Atypical granulocytopenia in clozapine treatment].

PMID- 8310098
TI  - [Recurrent leukopenia in therapy with levomepromazine].

PMID- 8310099
TI  - Prevention as cumulative protection: effects of early family support and
      education on chronic delinquency and its risks.
AB  - A cumulative protection model is proposed to explain why chronic juvenile
      delinquency may be amenable to prevention and how early family support and
      education may help achieve this important societal goal. A comprehensive review
      of early risk factors for chronic delinquency is presented with special attention
      to interactive effects. Interventions combining comprehensive family support with
      early education may bring about long-term prevention through short-term
      protective effects on multiple risks. A review of the early intervention
      literature reveals that the family support component is associated with effects
      on family risks, while the early education component is associated with effects
      on child risks. Both components may be necessary for effects on multiple risks
      and later reductions in delinquency. Implications for social policy and
      improvement of Head Start are discussed.

PMID- 8310100
TI  - Meta-analysis of P300 amplitude from males at risk for alcoholism.
AB  - The P3(00) event-related brain potential (ERP) is used to study the development
      of alcoholism by comparing males who have a positive family history of alcoholism
      with control Ss who have no such familial history. Meta-analysis indicated that
      overall, smaller P3 amplitudes were obtained from males with family histories of
      alcoholism compared to controls. Moderator analysis indicated that paradigms
      using difficult visual tasks yielded the most reliable effects. Furthermore, no
      differences in outcomes were obtained among studies that recruited positive
      family history Ss exclusively from among individuals whose father had received
      treatment for alcoholism as compared with other studies. These findings are
      discussed in the context of using ERPs as an evaluative tool in the study of
      psychopathology.

PMID- 8310101
TI  - The time course of attentional zooming: a comparison of voluntary and involuntary
      allocation of attention to the levels of compound stimuli.
AB  - The time course of attentional zooming between the levels of hierarchically
      structured compound stimuli (level-specific covert orienting of attention) is
      explored experimentally. The experiment compares the RT-SOA functions of
      voluntarily and involuntarily initiated level-specific reorienting within a cost
      benefit experiment using level-specific cues. With respect to the two modes of
      initiation, the results reveal no functional differences between attention shift
      and attentional zooming. Both can be initiated either voluntarily or
      involuntarily, the latter mode dominating the former; for both, involuntary
      initiation produces faster reorienting of attention than does voluntary
      initiation, and for both, involuntary initiation is more effective than voluntary
      initiation. However, the time needed to complete attentional orienting is about
      twice as long for zooming than for shifts. This quantitative difference suggests
      that there is a functional difference between level-specific and horizontal
      covert orienting. The difference is explained by postulating that zooming and
      attention shifts differ in the number of parameter sets that have to be adjusted
      in the reorienting of attention. The experiment also reveals that attentional
      zooming to the local level needs more time than does zooming to the global level.
      This result gives some support to the hypothesis that the RT difference between
      global and local identifications (Navon's global-dominance phenomenon) is due to
      an additional step in the course of reorienting attention away from the global
      level (which is usually attended to first) to the local level, when this level is
      to be identified.

PMID- 8310102
TI  - Differential effects of visual-spatial attention on response latency and temporal
      order judgment.
AB  - Theorists from both classical structuralism and modern attention research have
      claimed that attention to a sensory stimulus enhances processing speed. However,
      they have used different operations to measure this effect, viz., temporal-order
      judgment (TOJ) and reaction-time (RT) measurement. We report two experiments that
      compared the effect of a spatial cue on RT and TOJ. Experiment 1 demonstrated
      that a nonmasked, peripheral cue (the brief brightening of a box) affected both
      RT and TOJ. However, the former effect was significantly larger than the latter.
      A masked cue had a smaller, but reliable, effect on TOJ. In Experiment 2, the
      effects of a masked cue on RT and TOJ were compared under identical stimulus
      conditions. While the cue had a strong effect on RT, it left TOJ unaffected.
      These results suggest that a spatial cue may have dissociable effects on response
      processes and the processes that lead to a conscious percept. Implications for
      the concept of direct parameter specification and for theories of visual
      attention are discussed.

PMID- 8310103
TI  - Space-based visual attention models and object selection: constraints, problems,
      and possible solutions.
AB  - One of the functions of visual attention is the selection of object information.
      This seems to be in line with an influential group of attentional models that
      assume that attentional selection is space based. These models assume that the
      selection of an object in vision is realized by selection of the location of that
      object. Whether this relatively simple idea of space-based attention and the
      corresponding, more elaborated space-based models are sufficient to handle
      selected constraints and problems of object selection is the main issue of this
      article. The first step toward an answer is to describe the common computational
      structure of space-based attentional models. Two model classes will be
      distinguished: capacity-limited models (e.g., Treisman, 1988; LaBerge & Brown,
      1989) and models that do not assume a capacity limitation (e.g., Van der Heijden,
      1992). Next, three kinds of task and data on object selection are introduced that
      are especially challenging for space-based models. The first type of data refers
      to experiments that require selection between overlapping objects. The second
      type of data concerns the influence of early perceptual grouping--a strong object
      defining factor--on late response competition, and the third type consists of a
      selection task in which a high-level (semantic) attribute defines an object and
      controls selection. In all three cases, problems of space-based models are
      analyzed and possible solutions are sketched. Finally, a brief evaluative summary
      is given.

PMID- 8310104
TI  - The role of position in object selection in vision.
AB  - Within contemporary visual-information-processing psychology, two classes of
      selective-attention theories can be distinguished: position-not-special theories
      and position-special theories. The position-not-special theories postulate that
      attentional selection by colour, by form, and by position are equivalent
      selective operations. The position-special theories assume that selection by
      position is more basic or direct than selection by colour or by form. Examples of
      both types of theory are briefly described, and irrelevant and relevant evidence
      is critically discussed. It is concluded that the relevant evidence is directly
      compatible with the position-special views and that the position-not-special
      theories require additional extraneous assumptions. The position-special model
      presented in Van der Heijden (1992) is elaborated in further detail. It is shown
      that this model is compatible with two important and often substantiated
      assumptions of the position-not-special theories: the assumption that pre
      attentive analysers organize the visual scene in objects against a background,
      and the assumption that visual-selective attention can be directed at objects
      isolated in this way. This position-special theory is a parsimonious theory
      because it can identify the mentalistic concept selective attention with the
      materialistic concept spatial position.

PMID- 8310105
TI  - Attentional distribution in visual space.
AB  - The horizontal extent of the visual attentive field was measured by the use of a
      two-choice-RT task and compatible and incompatible distractors. The target was a
      line that inclined either to the left or to the right. Whether or not the subject
      performed the choice RT was made contingent upon whether two other stimuli
      presented in the visual display matched or mismatched. The match-mismatch stimuli
      varied in locations so as to manipulate the relevant visual area (the attended
      area). The locations of the distractors were also varied. The increase in RT
      associated with incompatible distractors was found to vary inversely with their
      distance from the edge of the area attended to and independently of their
      distance from the target lines. The results were interpreted in terms of an
      inhibitory field that surrounds the area attended to.

PMID- 8310106
TI  - Blood platelet responsivity to acute mental stress.
AB  - To evaluate the effects of mental stress on blood platelet activity, platelet
      secretion and aggregation were measured in 40 healthy young men, assigned in a
      3:1 ratio to an experimental and control condition. After a baseline period,
      experimental subjects participated in a 21-minute, frustrating computer task (the
      Stroop test), while control subjects remained seated quietly for the same
      duration. Blood was drawn from all subjects immediately before and after the task
      period for assessment of platelet activity (secretion of ATP and aggregation in
      response to 5 and 20 microM ADP). Heart rate and blood pressure were also
      assessed at baseline and throughout the task period. Results indicated that
      measures of platelet secretion, heart rate, and blood pressure rose significantly
      from baseline to posttask assessments in subjects exposed to the experimental
      stressor (p < .05), but not among controls. These findings are consistent with
      the hypothesis that stress may potentiate coronary disease pathogenesis, in part,
      via activation of blood platelets and their associated effects on coronary artery
      occlusion and/or constriction.

PMID- 8310107
TI  - Blood platelets, stress, and cardiovascular disease.

PMID- 8310108
TI  - Psychopathology and social functioning in men prenatally exposed to
      diethylstilbestrol (DES).
AB  - Previous research has suggested increased psychopathology in prenatally
      diethylstilbestrol (DES)-exposed persons. The current study compares the
      psychiatric histories and social functioning of 27 men with a history of high
      dose prenatal DES exposure and their unexposed brothers. We expected DES subjects
      to show greater lifetime psychopathology and poorer social functioning than
      controls. Both groups showed high rates of lifetime depression, lifetime
      alcoholism, and current psychiatric symptoms in excess of community norms. The
      only diagnosis on which DES subjects exceeded their unexposed brothers was Major
      Depressive Disorder (MDD). DES-exposed men had almost twice the prevalence of at
      least one episode of MDD and had significantly more recurrent episodes. The
      relatively small number of subjects with concomitant lack of statistical power
      may have contributed to the difficulty obtaining significant effects.

PMID- 8310109
TI  - Acute effects of laboratory stress on blood glucose in noninsulin-dependent
      diabetes.
AB  - The acute effects of two psychological stressors (personally stressful imagery
      and threat of shock) on blood glucose (BG), heart rate, blood pressure, skin
      conductance, and subjective stress were studied in 22 noninsulin-dependent
      diabetic adults and nine healthy, nondiabetic subjects similar in age, weight,
      education and sex. The diabetic group's BG rose significantly after threat of
      shock (M change from rest = 18.4 mg/dL, p < .05), although the nondiabetic
      group's BG remained stable throughout the assessment. Significant increases in
      subjective stress ratings (p < .05) and skin conductance level (p < .05)
      paralleled the noninsulin-dependent diabetes mellitis (NIDDM) subjects' BG
      response to threat of shock. The findings suggest that some stressors can have
      hyperglycemic effects on individuals with NIDDM, although generalization of these
      findings to the natural environment remains to be demonstrated. The methodology
      used is contrasted with other studies that have failed to demonstrate stress
      effects on BG.

PMID- 8310110
TI  - Cardiovascular and neuroendocrine responses to extended laboratory challenge.
AB  - The purpose of this study was to examine the effects of a 2-hour laboratory
      challenge on heart rate, blood pressure, catecholamines, and cortisol; and
      investigate the contribution of the physical act of speaking on both
      neuroendocrine and cardiovascular measures. Using a within-subjects design, 14
      subjects were tested individually during two separate laboratory sessions. During
      one session, subjects engaged in two cognitively demanding tasks for 2 hours.
      During the other session, subjects executed the verbal demands of the tasks for 2
      hours, but cognitive demands were absent. During both sessions, blood pressure
      and heart rate were measured and arterialized blood samples were obtained for the
      measurement of epinephrine, norepinephrine, and cortisol. Subjects demonstrated
      significantly greater increases in systolic blood pressure diastolic blood
      pressure, heart rate, epinephrine, and cortisol during the cognitively
      challenging session than during the control session. It is concluded that
      sustained elevations in cardiovascular and neuroendocrine measures can be
      achieved in the laboratory, and that the effects of such tasks cannot be
      attributed solely to the physical demands of speaking. Implications for the
      measurement of circulating catecholamines and cortisol during laboratory studies
      are discussed.

PMID- 8310111
TI  - Hemodynamic adjustments to laboratory stress: the influence of gender and
      personality.
AB  - Exaggerated cardiovascular reactivity to psychological stress is a potential
      pathophysiological mechanism linking behavior and cardiovascular disease. Because
      of the recognized gender differences in incidence of cardiovascular disease,
      potential gender differences in cardiovascular reactivity to laboratory stressors
      have been evaluated. The current study examined the cardiovascular responses of a
      total of 42 young women (N = 22) and men (N = 20) undergoing a laboratory
      protocol including the following: a nonverbal math task, a mirror tracing task,
      the Stroop Color-Word interference task, and an isometric handgrip task. In
      addition to the assessment of heart rate and blood pressure, cardiac output,
      stroke volume, total peripheral resistance and preejection period were assessed
      by impedance cardiography. A number of personality characteristics that vary in
      prevalence by gender were also measured to evaluate their ability to explain
      potential gender differences in cardiovascular responses. Results indicated that
      men responded with greater total peripheral resistance and systolic and diastolic
      blood pressure responses than did women on a subset of tasks, whereas women
      exhibited larger increases in heart rate on a subset of tasks. Thus, men were
      more likely to be "vascular" reactors, with women being more likely to be
      "cardiac" reactors. Personality characteristics did differ between men and women,
      but did not explain significant variance in the gender differences in
      cardiovascular responses. We conclude that additional studies should focus on
      experimental manipulations of potential physiological mechanisms responsible for
      these differences, such as reproductive hormones.

PMID- 8310112
TI  - Social support lowers cardiovascular reactivity to an acute stressor.
AB  - This study examined whether social support can reduce cardiovascular reactivity
      to an acute stressor. College students gave a speech in one of three social
      conditions: alone, in the presence of a supportive confederate, or in the
      presence of a nonsupportive confederate. Systolic and diastolic blood pressure
      were measured at rest, before the speech, and during the speech. While
      anticipating and delivering their speech, supported and alone subjects exhibited
      significantly smaller increases in systolic and diastolic blood pressures than
      did nonsupported subjects. Supported subjects also exhibited significantly
      smaller increases in systolic blood pressure than did alone subjects before and
      during the speech. Men had higher stress-related increases in blood pressures
      than did women; but gender did not moderate the effects of social support on
      cardiovascular reactivity. These results provide experimental evidence of
      potential health benefits of social support during acute stressors.

PMID- 8310113
TI  - Effects of acute mental stress on serum lipids: mediating effects of plasma
      volume.
AB  - The present study assessed the acute effects of mental stress (mental arithmetic)
      on serum cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL
      C), and low-density lipoprotein-cholesterol (LDL-C), and the extent to which
      stress-induced changes are attributable to decreases in plasma volume. Total
      cholesterol, triglycerides, HDL-C, and LDL-C were assessed in 18 healthy men (35
      +/- 7 years) during a resting baseline (30 minutes), challenging mental
      arithmetic (math; 10 minutes), and recovery (30 minutes). Five additional
      subjects served as controls receiving no stress intervention. An indirect
      estimation of the change in plasma volume was computed from hematocrit and
      hemoglobin at each time point. Results indicated significant (p < .001) increases
      in cholesterol, triglycerides, LDL-C, and HDL-C levels during mental arithmetic.
      Changes in lipid levels during stress were not related to plasma epinephrine
      levels or changes. Significant (p < .002) increases in hematocrit and hemoglobin
      levels reflected a 9.23% decrease in plasma volume during mental arithmetic.
      Correcting for this decreased plasma volume, changes in cholesterol,
      triglycerides, HDL-C, and LDL-C levels during math were no longer significant (p
      > .16, p > .23, p > .27, and p > .42, respectively). These results indicate that
      acute psychological stress can cause a rapid and substantial decrease in plasma
      volume, producing hemoconcentration. Thus, stress-mediated increases in
      circulating lipid concentrations are a secondary result of decreased plasma
      volume, perhaps due to vascular fluid shifts. Methodologically, stress-induced
      hemoconcentration during mental stress suggests that acute plasma volume
      decreases may need to be evaluated in studies of the biochemical effects of
      stress on high molecular weight substances.

PMID- 8310114
TI  - A Minnesota Multiphasic Personality Inventory profile of women with allergic
      rhinitis.
AB  - The aim of this study was to explore relationships among perennial allergic
      rhinitis and personality traits in a nonpsychiatric female population of proven
      allergic status. Female subjects were assigned to the allergic (N = 22) or
      nonallergic group (N = 18) on the basis of skin prick test and self-reported
      allergic status. Analysis of MMPI profiles showed that allergic subjects scored
      significantly higher on the Hypochondriasis (Hs) and Social Introversion (Si)
      scales and significantly lower on the Correction (K) and Ego Strength (Es)
      scales. The results suggested that women with perennial allergic rhinitis show
      poorer psychological functioning than nonallergic women. In addition, the number
      of allergies was positively correlated with T scores on the Hs, Depression (D),
      Hysteria (Hy), Psychasthenia (Pt), Schizophrenia (Sc), Si, and Conscious Anxiety
      (A) scales, and negatively correlated with T scores on the K and Es scales. Skin
      reactivity to house dust mite and grass pollen allergens were positively
      correlated with scores on Si, whereas skin reactivity to grass pollen and mold
      allergens was positively correlated with D and Pt (grass) and Pd and Sc (grass
      and mold). Two possible mechanisms explaining the link between psychological
      factors and allergic rhinitis include (1) the effect of cortisol on IgE
      production or (2) the production of mediators during an allergic reaction which
      travel from the nose to the brain.

PMID- 8310115
TI  - Development of child-centered disease-specific questionnaires for living with
      asthma.
AB  - Contemporary developments in the management of chronic diseases such as diabetes
      and asthma offer possibilities for optimal control, but patients increasingly
      need to take on responsibilities for self care. Health professionals require
      comprehensive assessments of outcome that include data reflecting patients'
      perceptions of their disorder and its management. Disease-specific, patient
      centered questionnaires for evaluation of adults' health-related quality of life
      are available for diabetes and asthma. Little progress is evident in relation to
      pediatric instruments. This paper describes the development of such an instrument
      for measurement of 8- to 11-year-olds' perceptions of their asthma--the CAQ-B
      Psychometric characteristics of the CAQ-B are reported: principal axis factor
      analysis resulted in the derivation of four subscales reflecting children's
      perceptions of both active and passive aspects of living with asthma, together
      with their perceptions of its severity and any associated distress. Preliminary
      explorations with CAQ-B included comparisons of parents', doctors', and
      children's ratings of severity; comparisons of data from asthmatic and
      nonasthmatic children; comparisons of data from boys and girls.

PMID- 8310116
TI  - Stronger relationship of hostility traits with myocardial ischemia in women.

PMID- 8310117
TI  - Unravelling the ecology of influenza A virus.
AB  - For 20 years after the influenza A virus was discovered in the early 1930s, it
      was believed to be almost exclusively a human virus. But in the 1950s closely
      related viruses were discovered in diseases of horses, pigs and birds.
      Subsequently influenza A viruses were found to occur frequently in many species
      of birds, particularly ducks, usually without causing disease. Researchers showed
      that human and animal strains can hybridise thus producing new strains. Such
      hybrids may be the cause of pandemics in man. Most pandemics have started in
      China or eastern Russia where many people are in intimate association with
      animals. This situation provides a breeding ground for new strains of influenza A
      virus.

PMID- 8310118
TI  - A bacteriological paradigm in influenza research in the first half of the
      twentieth century.
AB  - Scholars have argued that the beginning of virology can be dated from the end of
      the 19th century: the discovery that some infectious agents could pass through
      ultrafilters produced a criterium to distinguish ultrafilterable viruses from
      infectious agents that are not filterable, e.g. bacteria. A filterable agent,
      claimed to be the cause of human influenza, was isolated in 1933. It will be
      argued in this paper, however, that the influence of a bacteriological paradigm
      on influenza research in the first half of the twentieth century was very
      powerful. Until the late 1940s influenza viruses were studied as infectious
      entities which, although filterable, were conceived of as analogous to bacteria.
      It was assumed that filterable viruses which infected animals were a kind of
      ultrabacteria. According to the bacteriological paradigm the assumed dependence
      of the filterable viruses on living cells was easy to account for. The second
      half of the 1940s saw the 'modern concept of virus' begin to be applied to the
      influenza viruses. Influenza vaccinations in 1946 did not appear to provide
      protection, from which it was concluded that the influenza virus is very
      variable. Furthermore, in 1946 and 1947 experimental studies were published,
      which indicated that the influenza virus may go through an eclipse during its
      multiplication: it disappears as an infectious agent. Viewed from this
      perspective, it was only by the second half of the 1940s that research on the
      influenza virus became emancipated from the bacteriological paradigm.

PMID- 8310119
TI  - [Mitochondrial morphogenesis in insects during meiosis and spermatogenesis: a
      comparative study between modern high resolution microscopy and historical data].
AB  - Spermatogenesis in cysts isolated from testes of Drosophila and morphogenesis of
      male germ cell mitochondria were observed in vitro and compared with their first
      description in the literature. Since Drosophila started to be used for laboratory
      research only at the beginning of the 20th century, publications dealing with
      other insects have been consulted for earlier periods. Formerly, results were
      usually obtained from squashed preparations. This technique causes many artifacts
      and only occasionally can intact cysts be observed. It was only after tissue
      culture technique and microscopes improved that in vitro observation of
      differentiating cysts became possible. However, thanks to acute observational
      skills and careful reasoning, former researchers already had a correct picture of
      the early development of male germ cell mitochondria. Modern high resolution
      microscopy confirmed their results.

PMID- 8310120
TI  - The discovery of cellular oncogenes.
AB  - Between 1975 and 1985 a series of experiments demonstrated that cancer, whatever
      its causative agent, is due to the activation, by modification or overexpression,
      of a family of genes highly conserved during evolution, called the cellular
      oncogenes. These genes participate in the control of cell division in every
      living cell. Their products belong to the regulatory network relaying external
      signals from the membranes towards the nucleus and allowing cells to adapt their
      division rate to the demand of the organism. These discoveries constitute what
      may be called the 'oncogene paradigm'. Although the existence of cellular
      oncogenes, assumed in early models of oncogenesis, was demonstrated as early as
      1976, we will show in this article that this discovery was not sufficient for the
      development of the new paradigm. We will describe its slow and complex formation
      between 1980 and 1985 followed by its rapid acceptance by the scientific
      community.

PMID- 8310121
TI  - Oncogenes of DNA and RNA tumor viruses and the origin of cellular oncogenes.
AB  - Oncogenes were first described as the genes of DNA tumor viruses responsible for
      in vivo and in vitro neoplastic transformation induced by such viruses. The first
      oncogenes described were the oncogenes of polyoma, SV40 and papilloma viruses.
      The polyoma virus oncogene has been designated the 'middle' T (tumor) antigen,
      whereas the SV40 oncogene is designated the 'large' T antigen. The large T of the
      polyoma virus can also be considered an oncogene, because it is capable of
      'immortalizing', but not transforming primary cell cultures. Other oncogenes of
      DNA tumor viruses are the E1A of adenoviruses and the E7 gene of papilloma
      viruses. It has been proposed that some of the oncogenes of DNA tumor viruses act
      by binding the products of tumor suppressor genes, such as the retinoblastoma
      gene product Rb. In general, the products of the oncogenes of DNA tumor viruses
      need the cooperation of other oncogenes to establish a completely transformed
      phenotype. Oncogenes have been discovered in all replication defective RNA tumor
      viruses, whereas they are not present in the genomes of replication competent RNA
      tumor viruses, which can also give rise to a neoplastic phenotype, in vivo, but
      by a different mechanism. The discovery of oncogenes in RNA tumor viruses has led
      to the concept that these oncogenes are actually present in the genomes of all
      eucaryotic organisms and have been transduced and, in some cases, modified by a
      retrovirus. The characterization of the oncogenes of acute transforming
      retroviruses has led to the present classification of oncogenes, which include
      genes coding for proteins having different functional properties, but all
      characterized by having some role in the pathway which regulates cell
      proliferation. The experimental approach of DNA transfection has led to the
      discoveries of some oncogenes already known from the genomes of retroviruses and
      also of some new oncogenes which had never been transduced by retroviruses. The
      knowledge derived from retrovirus research and from the use of the DNA
      transfection technique has opened a whole new field of science thereby
      contributing greatly to our understanding of the mechanisms underlying neoplastic
      transformation and also to the understanding of normal cell physiology.

PMID- 8310122
TI  - Strategy and tactics in radiobiological research. Comments on a recent article by
      J.T. Lett.

PMID- 8310123
TI  - Model of mammalian cell reproductive death. I. Basic assumptions and general
      equations.
AB  - A systemic model describing the major radiobiological effects of various types of
      radiation is proposed. The model base lines were substantiated, and general
      mathematical equations for cell survival developed. The model takes into
      consideration such physical and biological factors as linear energy transfer, ion
      track structure, and structural and functional organization of interphase
      chromatin. This paper presents the basic assumptions made and general equations
      for the cell killing.

PMID- 8310124
TI  - Model of mammalian cell reproductive death. II. Comparison with experimental data
      and discussion.
AB  - A general equation for mammalian cell survival has been derived in the previous
      paper. This paper presents the results of comparison of theoretical evaluations
      with survival data available from the literature, including different cell lines,
      variations in linear energy transfer, dose rate and dose fractionation effects
      and the effects of ultrasoft X-rays and superheavy ions. Merits and demerits of
      the model are considered in comparison with other models of radiation-induced
      killing of mammalian cells published in the literature.

PMID- 8310125
TI  - Optimum inactivation dose and indices of radiation response based on the linear
      quadratic survival equation.
AB  - For typical tumor-cell dose-response curves, the efficiency ratio, i.e., the
      ratio between the fraction of cells killed and the radiation dose administered,
      is a continuously decreasing function of dose. However, if the survival curve is
      sufficiently "shouldered", this ratio has a maximum value at a dose greater than
      zero. In radiotherapy, one possible criterion for the ideal dose per session is a
      high value of the efficiency ratio for the targeted cells, but a low value for
      surrounding healthy cells. Efficiency ratios can be derived from dose-response
      relationships. Any linear quadratic dose-survival curve of the form S = exp(
      alpha D + beta D2) can be completely described by two parameters, s and phi,
      where s = alpha + square root of beta and phi = square root of beta/s. The former
      parameter is an index of radiosensitivity, and the latter is an index of curve
      shape. Using these indices, the ratio of fraction of inactivated cells to dose
      can be calculated and its maximum, as dose varies, determined. For values of phi
      greater than 0.55, this ratio has a maximum when the dose is approximately 1/s.
      However, for values of phi less than 0.4, this ratio is greatest when the dose is
      zero. Since phi varies widely among different cell lines, it may be possible to
      optimize radiotherapeutic dose-fractionation regimes using these indices. The
      parameterization of dose-survival relationships in terms of s and phi also
      simplifies conceptualization of the survival-curve characteristics. Both the mean
      inactivation dose and the dose required to reduce survival to 1/e are
      approximately equal to 1/s.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8310126
TI  - Stable chromosome aberrations 25 years after severe accidental radiation
      exposure.
AB  - A thorough cytogenetic analysis using G-banding was performed on 100 peripheral
      blood lymphocytes from an individual who had been accidentally exposed to
      radiation more than 25 years previously. More than 60% of the analysed cells were
      found to possess one or more stable chromosome aberrations (e.g. reciprocal
      translocations). Chromosomes 1 and 11 were more involved in these aberrations
      than would be expected from the relative chromosome lengths. No identical stable
      aberrations were found, suggesting that, 25 years after near-lethal exposure,
      haemopoietic stem cells display substantial diversity.

PMID- 8310127
TI  - Analysis of chromosomal aberrations, sister chromatid exchanges and micronuclei
      among power linesmen with long-term exposure to 50-Hz electromagnetic fields.
AB  - Chromosomal aberrations, sister chromatid exchanges (SCEs), replication indices
      and micronuclei in peripheral blood lymphocytes were analysed among 27 nonsmoking
      power linesmen with considerable long-term exposure to 50-Hz electromagnetic (EM)
      fields, and among 27 nonsmoking telephone linesmen serving as a reference group,
      pairwise matched with the exposed workers for age and geographical region. Blood
      samples from the two groups were collected, cultured and analysed in parallel. No
      differences between the groups were observed on analysis of SCEs, replication
      indices or micronuclei. However, the mean rate of lymphocytes with chromatid-type
      breaks was higher among the power linesmen (0.96% gaps excluded, 1.41% gaps
      included) than among the reference group (0.44% and 0.70%, respectively). The
      excess of aberrant cells was concentrated among those power linesmen who had
      worked earlier in their life. Although the interpretation is somewhat complicated
      by the confounding effect of previous smoking, these results suggest that
      exposure to 50-Hz EM fields is associated with a slight increase in chromatid
      breaks.

PMID- 8310128
TI  - N-acetylcysteine and captopril protect DNA and cells against radiolysis by fast
      neutrons.
AB  - N-Acetylcysteine and captopril, respectively mucolytic and antihypertensive
      drugs, contain free sulfhydryl groups. Since in general thiols have well
      established radioprotective abilities, we sought putative radioprotective effects
      of these drugs against therapeutic fast neutrons. We show that pBR322 plasmid DNA
      is indeed protected against radiolytic strand breakage by both drugs. The oxygen
      independent protection is consistent with a hydroxyl radical scavenging
      mechanism. A clonogenicity assay reveals an increase of the survival of SCL-1
      cultured keratinocytes irradiated in the presence of the drugs compared with
      cells irradiated without drugs. Our results suggest possible interferences
      between treatment with drugs bearing-SH groups and radiotherapy.

PMID- 8310129
TI  - Effect of gamma-irradiated carbohydrates on isolated synaptic membranes.
AB  - The effect of gamma-irradiated solutions of carbohydrates, mainly glucose, upon
      Na+, K(+)-ATPase and lipid peroxidation in rat brain synaptosomal membranes was
      studied. The membrane damage by irradiated glucose was enhanced in the presence
      of Fe2+ and was diminished when a free-radical scavenger (BHT) or metal chelators
      (EDTA, EGTA) were present. It is suggested that a key element in the free-radical
      membrane damage by irradiated carbohydrates is an Fe(2+)-complex of some species
      of the radiolysis products. Participation of radiotoxins of carbohydrate origin
      in radiobiological effects is discussed.

PMID- 8310130
TI  - Studies on the constancy of the blue and green fluorescence yield during the
      chlorophyll fluorescence induction kinetics (Kautsky effect).
AB  - Blue (F450) and green (F530) leaf fluorescence were studied together with the red
      chlorophyll fluorescence (emission maxima F690 and F735) during light-induced
      chlorophyll fluorescence induction kinetics (Kautsky effect) in predarkened
      leaves of wheat (Triticum aestivum L.) and soybean (Glycine max L.). The
      intensity of the red chlorophyll fluorescence decreased from maximum fluorescence
      Fm to steady-state fluorescence Fs, and the fluorescence ratio F690/F735
      decreased by about 10% from Fm to Fs. However, blue and green fluorescence
      intensities remained constant throughout the measuring time. Consequently, the
      ratio of blue to red fluorescence (F450/F690) increased during chlorophyll
      fluorescence induction kinetics, whereas the ratio of blue to green fluorescence
      (F450/F530) remained unchanged within the same period. The knowledge of these
      ratios will be a prerequisite for the interpretation of remote sensing data from
      terrestrial vegetation.

PMID- 8310131
TI  - [Methodology and reconstruction].

PMID- 8310132
TI  - [Psychoanalysis and early childhood research. Some basic topics of the debate].
AB  - In Dornes' view it is time for psychoanalytic development psychology to stand
      back from its preoccupation with the reconstructed child and gain access to the
      real child via direct observation, thus re-establishing contact with the state of
      research in neighbouring disciplines. Such direct observation would both
      stimulate a review of the cogency of the symbiosis and borderline theories of
      normal early development and question the assumption of lack of psychic
      differentiation in newborn children. So far, the author contends, psychoanalytic
      theory has both underestimated and overestimated the abilities of infants,
      ascribing to them in the latter case the capacity for complicated psychic
      operations (hallucinatory wish fulfillment, grandeur fantasies, projective
      identifications) which are in fact beyond their powers.

PMID- 8310133
TI  - [Theoretical conclusions and the "new psychoanalytic theories of the infant"].

PMID- 8310134
TI  - [Comments on psychogenic autism].

PMID- 8310135
TI  - Dose-volume effects in the spinal cord.
AB  - Experimental data on dose-volume relationships for the spinal cord are now
      available for a variety of animal models (monkey, dog, pig, rat). Most studies
      show a marginal volume effect for cord lengths longer than 1 cm, but a steep
      increase in tolerance doses for irradiated lengths of less than 1 cm. From a
      comparison of several theoretical models with available clinical/experimental
      data it can be concluded that there is at present no need for a further expansion
      of models, but a great need of reliable data.

PMID- 8310136
TI  - A new method to determine dose-effect relations for local lung-function changes
      using correlated SPECT and CT data.
AB  - PURPOSE: To determine dose-effect relations for regional lung-function changes
      after radiotherapy. METHODS: Single Photon Emission Computed Tomography (SPECT)
      was performed to quantify regional ventilation and perfusion. CT scans were used
      to calculate the three-dimensional (3-D) dose distribution. Both SPECT and CT
      scans were performed prior to radiotherapy and 5 months after the start of the
      treatment. To obtain combined 3-D information on ventilation, perfusion and dose,
      the SPECT data were correlated with the corresponding CT data. The relative
      changes in ventilation and perfusion were calculated in each SPECT voxel (voxel
      size about 6 x 6 x 6 mm) and related to the dose in that voxel. The average
      relative changes were determined per dose interval of 4 Gy. This procedure was
      evaluated using the data from five patients treated for Hodgkin's disease with
      mantle field irradiation with a prescribed total dose of 40-42 Gy. RESULTS: Dose
      effect relations for perfusion were observed in all patients, while in four of
      the five patients, a dose-effect relation was found for ventilation. The maximal
      uncertainty of the calculated radiation dose was 11%: a difference between the
      position of the patient during treatment and during CT scanning caused a maximal
      dose uncertainty of 6%, while the accuracy of the dose calculation algorithm
      itself was estimated to be within 5%. CONCLUSION: The results indicate that the
      combined use of SPECT and CT information is an effective method for determining
      dose-effect relations for regional lung function parameters in each individual
      patient.

PMID- 8310137
TI  - Conformal radiotherapy of the pelvis: assessment of acute toxicity.
AB  - During the last 3 years the Royal Marsden Hospital (RMH) has conducted a
      prospective randomised trial of conformal pelvic radiotherapy in which
      dose/volume data and acute toxicity scores have been determined prospectively.
      Pending completion of the trial, a preliminary analysis has been undertaken of
      the volume reductions achieved, and of some of the symptom scores. The average
      symptom score increased during radiotherapy, more markedly for bowel than bladder
      symptoms. In comparing total doses of 30-38 Gy with 56-65 Gy, watery bowel
      motions were more frequent with the higher doses (p = 0.013) but in the high-dose
      group neither this symptom nor tenesmus correlated with volume of rectum treated
      to at least 90% of the prescribed dose. We conclude that the assessment of the
      impact of volume on the level of acute symptoms in pelvic radiotherapy is
      complex, and requires analysis of a range of symptoms, dose levels and normal
      tissue volumes. The degree of symptom reduction from conformal radiotherapy will
      emerge from the RMH randomised trial within the next 12 months.

PMID- 8310138
TI  - Perspectives of multidimensional conformal radiation treatment.
AB  - We consider the present technological advancement that underlies the
      implementation of computer-controlled conformal radiotherapy. We also consider
      the developments in modern biology that may provide input to therapy planning.
      The concept of multidimensional conformal radiotherapy is advanced, which
      integrates geometrical precision and biological conformality, to optimize the
      treatment planning for individual patients, with a view to improve the overall
      success of radiotherapy.

PMID- 8310139
TI  - Implementation of a model for estimating tumor control probability for an
      inhomogeneously irradiated tumor.
AB  - This paper presents the details of a practical implementation of a model for the
      prediction of the tumor control probability (TCP) when a tumor is irradiated non
      uniformly. The implementation is based on a previously published model and
      represents a simplified version of the model with a limited number (five) of
      parameters. We show how to derive the model parameters from clinically available
      data and offer pseudocode for computer implementation. The model should be a
      useful tool for evaluating and optimizing 3D dose distributions.

PMID- 8310140
TI  - The clinical value of different treatment objectives and degrees of freedom in
      radiation therapy optimization.
AB  - With inverse radiation therapy planning methods, both biological and physical
      objective functions can be used to perform the optimization. A biological
      objective function, namely the probability of achieving tumor control without
      causing severe complications in normal tissues, P+, has been used to evaluate six
      different optimization methods. All six methods have been tested on two different
      clinically relevant treatment geometries. The results show that optimization with
      a physical objective function which gives the best possible agreement with the
      desired dose distribution in the least squares sense, may result in severe loss
      of complication-free tumor control due to insufficient consideration of the
      organs at risk. It is generally better to use a physical objective function which
      minimizes the over-dosage when the desired dose distribution can not be exactly
      reproduced. In all cases the use of physical objective functions results in a
      lower probability of controlling the tumor without causing severe normal tissue
      reactions than if the biological objective function, P+, is used. However, the
      results also show the importance of accurately accounting for beam divergence,
      dose build-up, beam attenuation, and lateral scatter during the optimization
      procedure, particularly when the biological objective function is used. The loss
      in P+ by assuming that all energy deposition kernels are identical and that all
      the constituent beams have fixed relative weights can be 15% or more. When
      lateral scatter is not accounted for during the optimization, serious injury to
      organs at risk may result. This problem is specially severe for organs that are
      partly or totally encapsulated by the target volume. For superficial target
      volumes accurate consideration of the dose build-up of the incident pencil beams
      is fundamental.

PMID- 8310141
TI  - High dose-high precision in radiation oncology.

PMID- 8310142
TI  - Quality assessment of medical decision making in radiation oncology: variability
      in target volume delineation for brain tumours.
AB  - The enormous developments in radiation technology open new horizons for
      improvements in local tumour control. However, the evolution from conventional
      external beam radiotherapy planning to conformal therapy might be hampered by the
      potential risk of over-reliance on the physician's capability of estimating the
      tumour extent from imaging modalities. The variability between 12 volunteering
      physicians in the delineation of tumour and target volume on the lateral
      orthogonal localisation radiograph from CT was assessed for 5 brain tumours. The
      estimated tumour and target sizes varied, respectively with a factor of 1.3-2.6
      and with a factor of 1.3-2.1. The anatomical location of the volumes showed
      maximum variations from 11 to 27 mm in the cranio-caudal direction and from 14 to
      21 mm in the fronto-occipital direction. For the 5 test cases, the tumour area on
      which all radiation oncologists agreed, represented only 25-73% of the
      corresponding mean tumour area. Although the introduction of computed tomography
      in radiation treatment planning was proved to be a major step forwards for
      treatment planning in many tumour sites, the results of the present study on
      brain tumours demonstrate that the subjective interpretation of the tumour extent
      based on CT images might be one of the largest factors contributing to the
      overall uncertainty in radiation treatment planning. Moreover, this study
      endorses the need for uncertainty analysis of the medical decision-making
      process. It may be that the process of making uncertainties explicit can
      contribute to the improvement of our present concept of radiation treatment
      planning.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8310143
TI  - Conformal external radiotherapy of prostatic carcinoma: requirements and
      experimental results.
AB  - The aim of conformal radiotherapy is to deliver, with high precision, a specific
      dose (which may be a high dose) to a planning target volume, concurrently with
      irradiating as little as possible healthy tissue and organs at risk. Radiation
      therapy may suffer from a number of problems that result in both over- or under
      sizing the irradiation fields, making over-rough simplifications of the
      irradiation ballistics and delivering an insufficient tumoral dose (to spare
      critical organs and reduce toxicity). One of these problems lies in the accurate
      positioning of the planning target volume with respect to the irradiation system,
      thence in the correct execution of the ballistics. In this paper, we describe a
      system aiming at achieving a higher overall accuracy in the delivery of prostatic
      boost for carcinoma of the prostate. The system is based on the use of ultrasonic
      images for measuring the actual position of the prostate just before irradiation.
      Since these images are registered with pre-operative (CT or MR) images, the
      position and orientation of the planning target volume is computed with respect
      to the irradiation system, and can be corrected accordingly. First experiments
      have been performed on dummies, and the results are discussed.

PMID- 8310144
TI  - The Royal Marsden Hospital pelvic radiotherapy trial: technical aspects and
      quality assurance.
AB  - Planning and quality control procedures are described for a randomised trial
      designed to measure the effect on normal tissue toxicity of reducing the volume
      of normal tissue irradiated through the introduction of Beams-Eye-View designed
      customised blocks. Consideration is given to the accuracy with which blocks can
      be designed and to the potential application of multi-leaf collimator technology.

PMID- 8310145
TI  - High technology to simplify the planning and delivery of radiotherapy.
AB  - Two techniques for the automatic selection of individual leaf positions of a
      Philips multi-leaf collimator are described. Target volumes are identified either
      on simulator images or on cross-sectional images from CT or MR scanners. The
      setting of each leaf is computed to position the beam edge to cover the target
      with an appropriate, user defined, margin. An important consideration in the
      development of the system was its robustness and so the applications initially
      implemented have been relatively simple, comprising single field, parallel
      opposed fields and coplanar 4 field box techniques. Attention has been paid to
      the overall integrity of the planning and treatment delivery process. Before
      treatment commences, the beam shapes, which have been generated by the computer
      and transferred to the MLC control computer over a local area network, are
      checked against a printed template representing each beam. All data used for
      planning is archived and is accessible for review or, if necessary, for treatment
      modification.

PMID- 8310146
TI  - Stereotactically guided fractionated radiotherapy: technical aspects.
AB  - A system for high precision radiotherapy in the head and neck region has been
      developed. The components of the system are a head mask connected to a
      stereotactic frame, a localization unit that can be used during CT- and MR
      imaging and a stereotactic target positioner. Conformal precision radiotherapy is
      planned with a new treatment planning system (Voxelplan-Heidelberg). Three
      different multi-leaf collimator systems are used. An evaluation of the precision
      and accuracy of the head fixation system, which was performed with a
      photogrammetry system, is presented.

PMID- 8310147
TI  - Fractionated stereotactically guided radiotherapy of head and neck tumors: a
      report on clinical use of a new system in 195 cases.
AB  - Between November 1988 and December 1992, 195 patients with tumors of the head and
      neck (low grade gliomas, meningiomas, neurinomas, chordomas and miscellaneous)
      were treated with a newly developed stereotactical system for fractionated,
      conformal, high-precision radiotherapy. The overall preparation time, including
      head mask production for fixation, CT, MRI, 3-D treatment planning and
      stereotactical localisation could be reduced to 4-5 h per patient. The use of MR
      in the target definition was increased to a mean of about 60%. The medial follow
      up time is 22 months. Three different patient groups were selected according to
      pretreatment. Patients with full high-precision radiotherapy survived in 95% of
      cases, patients with boost treatment in 86% and patients with preirradiated
      recurrent disease in 64%. Meningiomas as the largest histology group (n = 62)
      showed partial response in 27% and complete response in 10% of cases. Progression
      occurred in two patients. All patients are alive. Acute side-effects were minimal
      and of the order of 10%, no late complications occurred despite tumor doses
      ranging up to 72 Gy. High-precision radiotherapy as it is performed in Heidelberg
      can be regarded as an effective, reliable and tolerable system for selected
      tumors of the head and neck.

PMID- 8310148
TI  - From radiotherapy to stereotactic radiosurgery: physical and dosimetrical
      considerations.
AB  - The aim of this presentation is to analyse the mechanical and dosimetrical
      parameters of the linear accelerator used in stereotactic radiosurgery. The use
      of the thimble and Markus chambers, TL and film in small field dosimetry are
      investigated. To determine the optimal irradiation technique and dose
      distribution, the dose volume to healthy tissue is considered.

PMID- 8310149
TI  - A comprehensive system for the analysis of portal images.
AB  - In recent years, several techniques for the processing and analysis of portal
      images have been developed. It is the aim of this study to integrate some of
      these techniques into one comprehensive system. An advantage of this approach is
      that clinical experience can be obtained with more than one technique and a
      comparison of the techniques becomes possible. The portal image analysis
      procedure is implemented in the following steps: preparation of the reference
      image, portal image field edge detection, field edge match, anatomy match and the
      presentation of the results. For most of these steps, several alternative methods
      (e.g., interactive and automatic) are implemented. In addition, two new
      visualisation techniques have been incorporated. The first is a method for
      combining the results of the analysis of multiple fields in two dimensions, e.g.,
      large and boost fields. The second is a method for three-dimensional
      reconstruction of beam setup data, as derived from portal image analysis, on
      arbitrary reconstructed slices of a CT scan. With the latter method, the effect
      of setup errors on complex treatments (e.g., matching fields) can be studied. The
      new system has been in clinical use in our institution for two years and has been
      used to analyse about 5000 clinical portal images. The operators could choose
      freely from several matching methods. For 83% of the images our automatic
      matching algorithm was used. When required, the result of this method was
      corrected using the interactive drawing on image match. Significant corrections
      (more than 1 mm translation or 1 degree rotation) were applied to 27% of the
      automatically analysed images.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8310150
TI  - Role of portal imaging in clinical radiotherapy: Florence experience.
AB  - A portal imaging device developed at the Netherlands' Cancer Institute (NKI) in
      Amsterdam was provided to the Radiotherapy Section of the University of Florence
      as a partner of a cooperative study on quality assurance (QUIRT) granted by the
      EC (AIM Project). The device was used for portal imaging in 30 patients treated
      for tumors of different sites (5 rectum, 6 prostate, 5 Hodgkin's lymphomas, 5
      head and neck tumors, 9 other sites). Portal images were obtained three times per
      week over the whole treatment period. An off-line quantitative analysis of
      discrepancies with respect to the simulation image was performed for the 5 rectum
      cases; a similar analysis was also done on the portal images of 4 rectal cases
      treated at the NKI in Amsterdam. The analysis proved capable of demonstrating the
      existence of some systematic errors in both centres and the different level of
      global accuracy between them. The on-line use of the device was also able to
      demonstrate some major errors of patient setup during the first session, which
      were immediately corrected.

PMID- 8310151
TI  - Measurement possibilities using an electronic portal imaging device.
AB  - A vital role in the quality control of radiotherapy is the use of portal imaging
      for verifying field size, shape, orientation and patient set-up. Coincidence of
      treated volume and target volume is imperative. Electronic portal imaging devices
      are effective at providing this verification. However, these devices are
      versatile enough to be used in other ways pertinent to the delivery of high
      quality, high precision radiotherapy. This paper examines two such ways: in
      assessing the reproducibility of a multileaf collimator system, and in
      determining exit doses in vivo. Configured as a dosimeter, the system shows a
      linear response with good dynamic range. Its high spatial resolution was used to
      show that leaf positioning was reproducible to within 0.5 mm for all tested
      gantry and collimator angles. Our preliminary results from this exit dosimetry
      technique demonstrate that, under specific conditions, doses can be determined to
      within 2.5% of that measured using silicon diodes or ion chambers.

PMID- 8310152
TI  - Pre- and intra-irradiation multimodal image registration: principles and first
      experiments.
AB  - Accurately repositioning the patient with respect to CT or MR images is essential
      for high precision radiotherapy. We show that portal images may be automatically
      registered with 3D pre-session data (typically morphological images like CT or MR
      images), thus enabling an automatic adjustment of the planned strategy to the
      actual position of the patient. Based on computer vision techniques, the
      principles of this new method of multimodal image registration are presented, and
      the first experiments with a phantom are analysed.

PMID- 8310153
TI  - A verification procedure to improve patient set-up accuracy using portal images.
AB  - The purpose of this study was to establish which level of geometrical accuracy
      can be obtained during radiotherapy, using portal image analysis, with a minimum
      number of patient set-up measurements and corrections. A set-up verification and
      correction procedure using decision rules for improving the set-up of a patient
      during radiotherapy was investigated by means of a computer simulation. In this
      simulation study, set-up deviations were assumed to be the sum of random and
      systematic deviations and varying ratios of random and systematic deviations were
      studied. The distribution of random deviations (SD equal to sigma) was assumed to
      be equal for all patients of a specific treatment site. Set-up deviations are
      measured during the first N consecutive fractions after the start of the
      treatment or after a patient set-up correction. A set-up is corrected when the
      deviation averaged over these measurements is larger than an N-dependent action
      level. This action level is specified by alpha/square root of N, in which alpha
      is a variable initial action level parameter. After the start of the treatment or
      after each correction, Nmax measurements are made to decide on a possible
      (further) correction. By varying alpha and Nmax, the relation between the overall
      accuracy and the workload has been analyzed. It was possible to obtain a
      resulting overall accuracy level which is almost independent of the initial
      distribution of systematic deviations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8310154
TI  - An algorithm for automatic analysis of portal images: clinical evaluation for
      prostate treatments.
AB  - The aim of this study is to assess the clinical value of an algorithm for
      automatic analysis of portal images by measuring the method's performance in a
      clinical study of treatment of prostate cancer. The algorithm is based on chamfer
      matching and measures displacements of patients relative to prescribed radiation
      beam positions. In this paper we propose a method to quantify the mean standard
      deviation (MSD) of the performance of automatic analysis relative to the MSD of
      the performance of trained radiographers using the clinical data set only, i.e.
      without using additional phantoms or simulations. The clinical data set in this
      study consists of 99 regional AP prostate images of 15 different patients. To
      assess the performance the automatic analysis in relation to that of the human
      observers, we studied the results of the unsupervised automatic analysis, as well
      as the results of a less-trained human observer and a well-trained human observer
      assisted by the automatic analysis (in this combination, automatic analysis is
      done first and the result is modified by the well-trained observer if the
      observer does not agree). First, the intra-observer variations of the well
      trained observer are measured by repetitive analysis of a small subset of the
      clinical data. The distribution of differences in analysis between two arbitrary
      observers is described by the chi 2 distribution, and is tabulated in literature.
      We define the agreement histogram of an observer O as an estimator for the chi 2
      distribution between O and the well-trained human observer, parameterized by the
      ratio of the intra-observer variations of O and the well-trained
      observer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8310156
TI  - The role of in vivo dosimetry.

PMID- 8310155
TI  - In vivo dosimetry during conformal therapy of prostatic cancer.
AB  - In vivo dose measurements were performed during the simultaneous boost technique
      for prostatic cancer to check the accuracy of dose calculations by a monitor unit
      calculation program and a three-dimensional planning system. The dose of the
      large field and the boost field are given simultaneously using customized 10 mm
      thick Roses-metal blocks in which the boost field is cut out. Following the
      procedure of the quality assurance protocol for this technique, the dose at the
      specification point has been determined by in vivo dosimetry. The measured dose
      was initially too high for 5 out of 16 patients, due to unexpected differences in
      two beams with the same nominal beam quality and a different density correction
      for the femoral heads; the monitor unit calculation program was therefore checked
      and improved. The dose at the specification point was also compared with
      calculations performed by a CT-based three-dimensional (3-D) planning system. The
      average deviation of the 3-D planning system from the measurements is 0.1% +/-
      1.2%. Entrance, midline and exit dose values in the central axial plane, in a
      cranial plane and in a plane under the transmission block have also been compared
      with calculations performed by the 3-D treatment planning system. The measured
      entrance dose is, on average, 3.4% higher than the calculated dose for the AP
      beam and up to 5.5% for the lateral beams. Phantom measurements were performed
      and showed that these differences were not related to patient set-up
      errors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8310157
TI  - The programme of quality assurance of the EORTC radiotherapy group. A historical
      overview.
AB  - A quality assurance programme was activated in 1982 in the EORTC Cooperative
      Group of Radiotherapy. Definitions and contents of quality assurance and quality
      control, definitions of errors and deviations (systematic, occasional) are given.
      The methodology and steps of the quality assurance programme adopted over the
      past ten years are briefly described. The need for an interaction between
      national and international networks is emphasized. Consensus statements on
      quality assurance in radiotherapy provided during the January 1993 Geneva meeting
      conclude this introduction to the detailed reports on the quality assurance
      programme of the EORTC Cooperative Group of Radiotherapy.

PMID- 8310158
TI  - Mailed TL dosimetry programme for machine output check and clinical application
      in the EORTC radiotherapy group.
AB  - The Radiotherapy group of the European Organisation for Research and Treatment of
      Cancer (EORTC-RT) has been performing quality assurance with mailed TL dosimetry
      since 1986. The programme consists of therapy machine output checks, in vivo
      measurements, and dosimetry for brachytherapy. The therapy machine output checks
      have revealed a few large deviations (greater than 7%) between EORTC-measured and
      institute-stated dose, but also shown an improvement in the dosimetry of the
      participating institutes as a result of consecutive mailings. The use of in vivo
      dosimetry with mailed TLD has proven that it is feasible to detect deviations of
      +/- 5%. The results have shown deviations within +/- 5% for dosimeters located
      well within the radiation field for internal measurements in the pelvic region.
      Dosimetry of brachytherapy has been performed for low dose rate 192Ir sources.
      Differences of 14% can be seen between the participating centres.

PMID- 8310159
TI  - EORTC radiotherapy group quality assurance: mechanical checks and beam alignments
      of megavoltage equipment.
AB  - In 1987 mechanical checks of megavoltage units and simulators were included in
      the on-site physics program of the EORTC. The results reported were obtained in
      16 different centres and concern 23 accelerators, 14 cobalt units and 14
      simulators. In general, the deviations observed for accelerators and simulators
      are smaller than for cobalt units. A single score, based on the deviations
      observed for the mechanical checks, is attributed to each centre.

PMID- 8310160
TI  - Preliminary results of a quality assurance network for radiotherapy centres in
      Europe.
AB  - Based on the IAEA/WHO experience in mailed dosimetry, a Quality Assurance (QA)
      Network, sponsored by the EC committee "Europe Against Cancer", has been set up
      in 1991 for European centres, not involved in clinical research. Besides a survey
      of radiotherapy infrastructure, the project includes three measurement steps:
      primarily a check of beam output and quality in reference conditions with a
      mailed TLD-procedure, in a second step the mailed verification of other beam data
      and dose calculation procedures with a multipurpose phantom and finally in vivo
      dosimetry at the individual patient levels with mailed dosimeters. The results of
      infrastructure show good agreement with the data previously published by EORTC
      for research centres. Until January 1993, a total number of 37 centres (49 X-ray
      beams and 28 cobalt beams) from Belgium, France, Italy, The Netherlands, Sweden
      and The Czech and Slovak Republics have participated in the first measurement
      step. Deviations > 3% and < 6% from the stated dose are found in 17 out of the 79
      checked beams. A deviation < 6% from the stated dose is detected in only 1 out of
      the 28 cobalt beams, but in 7 of the 49 X-ray beams. The large majority of the
      beams (23/25) with deviations > 3% belong to centres not having participated in
      external audits in the previous 5 years. A pilot study for the second step shows
      larger deviations in non reference conditions, especially for off-axis points and
      for oblique phantom surface. The third step has yet to be implemented.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8310161
TI  - Uncertainties in pharmacokinetic modeling for perchloroethylene: II. Comparison
      of model predictions with data for a variety of different parameters.
AB  - In this paper we compare expectations derived from 10 different human
      physiologically based pharmacokinetic models for perchloroethylene with data on
      absorption via inhalation, and concentrations in alveolar air and venous blood.
      Our most interesting finding is that essentially all of the models show a time
      pattern of departures of predictions of air and blood levels relative to
      experimental data that might be corrected by more sophisticated model structures
      incorporating either (a) heterogeneity of the fat compartment (with respect to
      either perfusion or partition coefficients or both) or (b) intertissue diffusion
      of perchloroethylene between the fat and muscle/VRG groups. Similar types of
      corrections have recently been proposed to reduce analogous anomalies in the fits
      of pharmacokinetic models to the data for several volatile anesthetics. A second
      finding is that models incorporating resting values for alveolar ventilation in
      the region of 5.4 L/min seemed to be most compatible with the most reliable set
      of perchloroethylene uptake data.

PMID- 8310162
TI  - Risk assessment for aflatoxin: an evaluation based on the multistage model.
AB  - Lifetime cancer potency of aflatoxin was assessed based on the Yeh et al. study
      from China in which both aflatoxin exposure and hepatitis B prevalence were
      measured. This study provides the best available information for estimating the
      carcinogenic risk posed by aflatoxin to the U.S. population. Cancer potency of
      aflatoxin was estimated using a biologically motivated risk assessment model. The
      best estimate of aflatoxin potency was 9 (mg/kg/day)-1 for individuals negative
      for hepatitis B and 230 (mg/kg/day)-1 for individuals positive for hepatitis B.

PMID- 8310163
TI  - Comparing toxicologic and epidemiologic studies: methylene chloride--a case
      study.
AB  - Exposure to methylene chloride induces lung and liver cancers in mice. The mouse
      bioassay data have been used as the basis for several cancer risk assessments.
      The results from epidemiologic studies of workers exposed to methylene chloride
      have been mixed with respect to demonstrating an increased cancer risk. The
      results from a negative epidemiologic study of Kodak workers have been used by
      two groups of investigators to test the predictions from the EPA risk assessment
      models. These two groups used very different approaches to this problem, which
      resulted in opposite conclusions regarding the consistency between the animal
      model predictions and the Kodak study results. The results from the Kodak study
      are used to test the predictions from OSHA's multistage models of liver and lung
      cancer risk. Confidence intervals for the standardized mortality ratios (SMRs)
      from the Kodak study are compared with the predicted confidence intervals derived
      from OSHA's risk assessment models. Adjustments for the "healthy worker effect,"
      differences in length of follow-up, and dosimetry between animals and humans were
      incorporated into these comparisons. Based on these comparisons, we conclude that
      the negative results from the Kodak study are not inconsistent with the
      predictions from OSHA's risk assessment model.

PMID- 8310164
TI  - Protocerebral deafferentation effects on crayfish glycemic response: a
      protocerebral circadian pacemaker regulates the hemolymph sugar concentration.
AB  - Similar to intact crayfish animals with an isolated protocerebrum exhibit a
      competent control for circadian variations of glucose concentration in the
      hemolymph. However, the sudden increase in glucose concentration induced by
      stressing influences in intact or partially deafferented animals dropped or
      became totally suppressed in the preparations with isolated protocerebrum.

PMID- 8310165
TI  - Effect of FADH2 on the hydrolytic activity of mitochondrial ATPase.
AB  - FADH2 affected mitochondrial ATPase activity of both F1 and the membrane bound
      enzyme. F1-ATPase activity increased in its presence, whereas that of the
      membrane bound enzyme decreased. These effects were more marked at low substrate
      concentrations. The inhibition of membrane bound ATPase activity was not reversed
      by ADP. However, the simultaneous presence of free ATP and FADH2 produced a
      stimulation of the membrane bound enzyme activity. The varying effect of FADH2 on
      the membrane bound ATPase activity, depending on ATP concentration, could be the
      expression of a physiological role in mitochondria.

PMID- 8310166
TI  - [Uptake and intraphagocytic activity of teicoplanin in human neutrophils].
AB  - The incorporation of antibiotics in phagocytes is necessary for their activity
      against intracellular microorganisms. The ability of Teicoplanin to enter in
      human polymorphonuclear leukocytes (PMNs) after infection with Candida albicans
      was investigated using an in vitro model previously described. Human PMNs were
      preincubated with Candida albicans for 30 min, after which antibiotic (100 mg/l)
      was added to cell suspension during 1, 5, 15, 30 and 60 min. The results were
      expressed as the ratio of the cellular concentration of antibiotic to the
      extracellular concentration (C/E). Teicoplanin bound rapidly to phagocytes (with
      a C/E = 2.12 after 1 min of incubation), being the cell-associated drug
      approximately similar during the entire incubation period. At the same time,
      Teicoplanin increases the percentage of mortality of Candida albicans previously
      ingested, which was dependent of the incubation period in its presence.

PMID- 8310167
TI  - Distortion product otoacoustic emissions in normally hearing subjects.
AB  - The finding of active function by the outer hair cells for sound processing prior
      to neural transduction in the inner hair cells represents the basic mechanism for
      the generation of Otoacoustic Emissions in the cochlea. Among them the so-called
      Distortion Product Otoacoustic Emissions represent a tool for an in depth
      knowledge of the Organ of Corti micromechanics, more advantageous than others,
      based on their properties, that makes possible an objective frequency-specific
      study: The response in a group of normally hearing subjects is presented and
      characterized to ascertain the basic features to be used in further testing of
      deaf people.

PMID- 8310168
TI  - Deficient testicular and adrenal steroidogenesis in mutant cream (e/e) Syrian
      hamsters.
AB  - Coat color genes have been shown to be developmental genes with wide pleiotropic
      actions. The present study was undertaken to analyze the effects of mutations at
      the e locus of the Syrian hamster on testicular and adrenal steroidogenesis.
      Although no differences in body weight were detected, cream (e/e) hamsters had
      larger testes and smaller adrenals than wildtype (+/+) animals. Plasma
      testosterone levels were lower in e/e than in +/+ hamsters. However; testicular
      progesterone levels were higher, and 17-OH-progesterone and testosterone levels
      were lower in e/e when compared to +/+ hamsters. The efficiency of testicular 17
      hydroxylase appear to be reduced in e/e hamsters. Adrenal progesterone levels
      were higher. 17-OH-progesterone, testosterone, dehydroepiandrosterone sulphate
      and aldosterone levels were similar, and cortisol levels were lower in e/e when
      compared to +/+ hamsters. The efficiencies of adrenal 17-hydroxylase and 17
      hydroxysteroid dehydrogenase appear to be reduced in e/e hamsters. The present
      data indicate that steroidogenic deficiencies are present in the testes and
      adrenals of e/e hamsters, and that the gonadal alterations are more severe than
      the adrenal ones. The e locus, in the hamster, could be a developmental gene, or
      could be coding for a component in a signaling pathway under the control of such
      a gene.

PMID- 8310169
TI  - [Maps of visually evoked brain electrical activity in rabbits].
AB  - A basic model of topographic distribution of the electric response visually
      evoked in rabbits by means of flashes (0.69 joules/flash) has been obtained. The
      model is composed of four main parts--N0, P1, N1 y P2--linked to the VI visual
      area and displayed on a dipole shaped. The dipole turnaround time oscillates
      between 20 and 25 ms. The use of electrical activity brain maps on the study of
      the PE makes it possible to notice the phenomenon simultaneousness, thus
      facilitating its interpretation. A multinomial interpolation method of continuous
      function has been used to perform the maps.

PMID- 8310170
TI  - Effects of L-arginine analogues in isolated cat cerebral arteries.
AB  - The possible contribution of nitric oxide (NO) to the endothelium-dependent
      relaxation of isolated cat cerebral arteries was studied by examining the effects
      of the L-arginine (L-ARG) analogues L-canavanine and NG-nitro-L-arginine (L
      NOARG) on acetylcholine-induced relaxation. L-canavanine (100 microM) as well as
      L-NOARG (10 microM) decreased significantly the relaxant response of
      acetylcholine, their effect being significantly reversed by L-arginine (10
      microM) but not by D-arginine (10 microM). In resting conditions, L-NOARG (10
      microM) elicited a contraction of 314 +/- 42 mg in arteries endowed with
      endothelium that was significantly diminished by endothelium removal to 88 +/- 35
      mg, and by (10 microM) L-arginine to 135 +/- 54 mg. L-canavanine (100 microM)
      induced contractions in arteries with and without endothelial cells which were
      not statistically different. The results suggest that the endothelium of cat
      cerebral arteries has the ability to synthesize nitric oxide from L-arginine and
      to release it, even in the absence of a stimulus such as that of acetylcholine. L
      NOARG seems to be a specific and powerful inhibitor of nitric oxide synthesis.

PMID- 8310171
TI  - [Solubility of 6 gases in blood and various liquid media].
AB  - Sulfur hexafluoride, ethane, cyclopropane, enflurane, diethyl ether and acetone
      are six gases commonly used in the measurement of the distribution of ventilation
      perfusion ratios. In order to obtain reference data, their liquid/gas partition
      coefficients (K) have been determined in water at three different temperatures
      and in several inorganic, organic and biologic media at 37 degrees C, by a
      headspace-gas chromatographic method. As expected, an increase in temperature and
      concentration of solutes in the liquid matrix reduces the solubility of the
      gases. All gases, except acetone, are more soluble in olive oil than in water.
      The solubility of SF6, ethane, cyclopropane and enflurane in human and rat blood
      is greater than in water, the solubility of ether remains practically unchanged,
      and that of acetone is lower in blood than in water.

PMID- 8310172
TI  - [Adolescents with autism syndrome and autistic manifestations in vocational
      education centers].
AB  - Young people with autistic syndrome or autistic traits have for some years also
      been included in vocational training centre programmes. The present study had
      been aimed at analyzing the experience gained during vocational rehabilitation
      service provision and at fathoming conditions for a successful training course
      and placement process. 10 centres reported their experience from vocational
      training of 29 autistic young people, with the following noted in conclusion: The
      vocational training centres primarily accept young people with qualified
      educational levels and moderate behavioural peculiarities. The training as a rule
      is completed successfully. During programme participation, however, considerable
      problems arise in acquiring social and communication skills as well as in
      cognitive respects. Notwithstanding successful training completion, only some 25%
      could be placed in appropriate employment in the general labour market.
      Communication problems, impact of vocational training centre infrastructure,
      supportive and follow-up services, preparation and follow-along of staff, as well
      as alternatives to current vocational education practices are discussed.

PMID- 8310173
TI  - [Medical and occupational rehabilitation of psychiatric patients. Results of
      concomitant research of rehabilitation facilities for psychiatric and handicapped
      patients].
AB  - The Rehabilitation facilities for mentally ill and disabled (RPK) are designed to
      enable clients with chronic mental illness to (re)acquire the skills needed for
      their reintegration in occupational and/or social respects. The peculiar feature
      of the RPKs is their holistic approach integrating medical-psychiatric care,
      vocational preparation and training services, as well as sociotherapeutic
      measures. Accompanying research findings clearly prove that, once they have
      gained a firm foothold in the RPK, the great majority of the rehabilitees will
      achieve successful and lasting rehabilitation. The medical phase is completed by
      some two thirds of the clients admitted. Drop-out usually occurs in the initial
      three months period. The medical phase is followed by medical-vocational services
      in approx. 60% of the rehabilitees, and the majority of these achieve successful
      reintegration, with a drop-out rate of 15-20% in this phase clearly below the
      rate during the medical service provision phase. RPKs operating along a
      cooperative model have proven their worth within a dense service provider
      network, while the advantages of the integrative model lie in its concentration
      of services under one roof. Recommendations given in particular pertain to
      simplification of admission procedures and to ensuring follow-up services after
      programme completion.

PMID- 8310174
TI  - [Subjective discomfort of stomach cancer and esophageal cancer patients in after
      care].
AB  - In the framework of a study on the rehabilitation needs in gastric and
      oesophageal cancer patients, 100 gastric and 100 oesophageal cancer patients were
      interviewed on their subjective emotional state and physical functioning. The
      potentially cured patients were admitted to our in-patient aftercare programme an
      average 9.5 months following primary treatment. Major psychological distress was
      reported by 69.5% of the patients. Brooding, unrest, nervousness, and insomnia
      were the most frequently named complaints in both groups. 93% reported physical
      limitations, and 80% felt their conditions of life more or less restricted by
      their disease. 50% of all patients reported lack of drive, 30% an inclination to
      withdraw and a basic attitude of resignation. No significant differences between
      gastric and oesophageal cancer patients were found concerning type and frequency
      of the complaint.

PMID- 8310175
TI  - [The Gailingen Scaffold Test--a stress trial for occupations with a risk of
      falling].
AB  - The Jugendwerk Gailingen's rehabilitees with severe craniocerebral trauma placed
      in open employment include some 10% who work in construction, electric and metal
      working industry occupations involving exposure to fall hazards, as a rule having
      returned to their previous occupations or following vocational training. During
      their rehabilitation, specific considerations have to be taken into account due
      to this hazard, both relative to work characterization and to rehabilitee
      remaining abilities and vocational assessment. Initially, the risk of falling
      must be identified, with subsequent estimation whether continuation of the hazard
      generating activity will presumably be possible and/or justifiable. In the
      affirmative, this is followed by vocational assessment, which, beyond work
      tolerance and capacities, also deals with fall safety. The necessary strength,
      mobility, coordination, attention, concentration, and flexibility are assessed
      using the so-called Gailingen scaffold test. Although this test simulates but a
      fraction of possible work situations above ground and does look relatively
      harmless compared to real worklife, more than 100 rehabilitees have achieved
      successful, lasting integration in a variety of occupations which partly involve
      a rather high exposure to fall hazards, without any accidents having been
      reported at follow-up.

PMID- 8310176
TI  - [Competitive sports for handicapped patients. Motivation--attitude--facts].
AB  - Selected findings are presented from an Emnid public opinion research institute
      study of n = 241 disabled competitive athletes. The majority of the interviewees
      engage in competitive sports for "pleasure in achievement", with their successes
      seen as confirmation of self and in turn entailing enhanced self-esteem and
      confidence in their own potential for achievement. On comparison with the
      performance of nondisabled competitive athletes, the majority of interviewees
      tend to consider their performance on a par. Disabled athletes hold the opinion
      that their public visibility constitutes a major contribution towards societal
      recognition of disabled persons. They hence also see themselves as widely
      accepted as competitive sportsmen/-women by society at large. Also, their
      sporting successes contribute to a higher standing among their friends and
      acquaintances. The disabled sportsmen and -women do not anticipate any health
      hazards on account of their training and competition participation. The interview
      findings outlined are discussed in light of current knowledge and experience in
      the field of disabled competitive sports.

PMID- 8310177
TI  - [Opinions of non-handicapped children about handicapped children--results of a
      survey in 2nd grade of elementary school].
AB  - It is pointed out in the initial theoretical considerations that comparatively
      few studies can be found in the pertinent literature that address the issue of
      younger non-disabled children's attitudes and behaviour toward children with
      physical disablement. The present study had comprised 23 second-year primary
      school-children (8 male, 15 female), age 7.6 to 8.6, from a community with a
      population of approx. 6000. At the time of our investigation, the subject of
      "disability" had not been explicitly dealt with at school, and the children
      moreover reported that they had not previously come into contact with disabled
      children either. The interviews were administered individually, using an
      interviewing structure of 19 questions pertaining to 7 different topics. Along
      with the findings for these 7 areas, the following can be summarized: The
      findings permit the conclusion that the majority of the children interviewed do
      not encounter disabled children in terms of an already manifest prejudiced
      behaviour. Restrictive opinions primarily have to do with functional limitations
      assumed to affect disabled children's abilities in play, are however unrelated to
      dimensions of the personality or a social behaviour that could entail rejection
      of the disabled child. On the other hand it was found that non-disabled children
      do anticipate the negative views held by others in their environment toward
      children with disabilities.

PMID- 8310178
TI  - The importance of the binding-protein-dependent Mgl system to the transport of
      glucose in Escherichia coli growing on low sugar concentrations.
AB  - Glucose limitation in chemostats derepressed the binding-protein-dependent Mgl
      transport system, which is strongly repressed during growth in batch culture with
      high glucose levels. The limitation-induced Mgl activity was higher than that of
      batch cultures "fully induced" for the Mgl system after growth on glycerol plus
      fucose. Mgl- strains were impaired compared to Mgl+ bacteria in removing glucose
      from sugar-limited chemostats and were outcompeted in mixed continuous culture on
      limiting glucose. The influence of Mgl was not observed on growth with limiting
      maltose or non-carbohydrates, and thus was specific for glucose, a known
      substrate of the Mgl system. In the absence of the two glucose-specific membrane
      components of the phosphoenolpyruvate:sugar phosphotransferase system, non-PTS
      dependent growth on glucose was observed in continuous culture, but only under
      sugar-limited conditions derepressing the Mgl system and not in glucose-rich
      batches or continuous culture. Hence growth of Escherichia coli on glucose at
      micromolar concentrations involves a significant contribution of a binding
      protein-dependent transport system. The participation of multiple transporters in
      glucose transport can account for the complex non-hyperbolic dependence of growth
      rate on glucose concentration and for discrepancies in studies attempting to
      describe growth on glucose purely in terms of phosphotransferase kinetics.

PMID- 8310179
TI  - Acetohydroxy acid synthase and threonine deaminase activities, and the
      biosynthesis of isoleucine-leucine-valine in Streptococcus bovis.
AB  - Acetohydroxy acid synthase (AHAS) and threonine deaminase (TD) activities were
      found in Streptococcus bovis and shown to be involved in the biosynthesis of the
      branched chain amino acids isoleucine, leucine and valine. Apparent lack of
      repression of AHAS synthesis by the end-products and reduced sensitivity of S.
      bovis growth to analogues of the branched chain amino acids suggested that
      secretion of isoleucine, leucine and valine in the growth medium may be a
      consequence of the regulatory features of AHAS. A glycyl-leucine-resistant mutant
      with reduced TD activity secreted a reduced amount of isoleucine and an increased
      amount of valine, which might be a result of the reduced rate of synthesis of the
      isoleucine precursor alpha-ketobutyrate and of a consequent preferential carbon
      flow through the valine branch of the pathway.

PMID- 8310180
TI  - Sequence of the gene coding for the neurotoxin of Clostridium botulinum type A
      associated with infant botulism: comparison with other clostridial neurotoxins.
AB  - The neurotoxin gene from a strain of Clostridium botulinum type A causing infant
      botulism was cloned as a series of overlapping polymerase chain reaction (PCR)
      fragments generated using primers designed to conserved regions of published
      botulinal toxin (BoNT) sequences. Translation of the nucleotide sequence derived
      from cloned PCR fragments demonstrated that the toxin gene encodes a protein of
      1,296 amino acid residues. Comparative alignment of the derived infant BoNT/A
      sequence with those of other published neurotoxins revealed highest sequence
      relatedness with BoNT/A of classical food-borne botulism. The sequence identity
      between infant and classical BoNT/A was 94.9% for the light chain (corresponding
      to 23 amino acid changes) and 87.1% for the heavy chain (corresponding to 109
      amino acid changes).

PMID- 8310181
TI  - Polymerase chain reaction for the specific detection of Escherichia
      coli/Shigella.
AB  - The outer membrane protein PhoE of members of the family Enterobacteriaceae
      consists of conserved membrane-spanning segments and hypervariable surface
      exposed regions. Two oligonucleotides based on DNA sequences encoding two
      different cell-surface-exposed regions of the Escherichia coli K12 PhoE protein
      were tested for their specificity in polymerase chain reactions. They reacted
      with all strains of the species E. coli/Shigella tested, except for strain S.
      boydii serovar 13, which is known to represent a different DNA-relatedness group.
      The probes did not react with any other Enterobacteriaceae tested, including
      strains of Escherichia blattae, Escherichia hermanii, Escherichia vulneris and
      Escherichia adecarboxylata, except for an Escherichia fergusonnii strain, which
      is most closely related to E. coli. Therefore, the primer couple showed a high
      degree of species-specificity. In addition, a second primer couple based on two
      conserved regions of the phoE genes was tested. This primer couple recognized a
      broad group of closely related enteric bacteria including Salmonella and
      Shigella.

PMID- 8310182
TI  - Glycerol uptake in Escherichia coli is sensitive to membrane lipid composition.
AB  - In Escherichia coli, a functional GlpF protein is necessary for efficient uptake
      of glycerol at low concentrations. Here we show that GlpF-mediated glycerol
      uptake was sensitive to a variety of lipid alterations. Overproduction or
      mutation of the genes coding for enzymes involved in lipid biosynthesis resulted
      in changed membrane composition and fluidity. The strains with altered lipid
      composition had a substrate affinity for glycerol (Km) similar to that of wild
      type cells, but the Vmax for glycerol uptake was affected. Experiments with
      glpF::lacZ and glpK::lacZ protein fusions showed that the expression of these two
      genes was not changed under these conditions. In addition, we observed that
      mutations in glpF were accompanied by reduced membrane permeability for compounds
      unrelated to glycerol. Passive diffusion across the membranes of glpF mutants for
      o-nitrophenyl galactoside was 5-fold slower than in glpF+ cells. The mutants were
      more resistant to the hydrophobic antibiotic tetracycline, as well as to the
      membrane perturbants ethanol and dimethylsulphoxide and to the stress of low
      osmolarity medium.

PMID- 8310183
TI  - Secretion of bacterial beta-lactamase into culture broth by a mutant strain of
      Saccharomyces cerevisiae.
AB  - The secretion of Escherichia coli beta-lactamase was studied in a Saccharomyces
      cerevisiae ts1 mutant strain. The signal sequence of pre-beta-lactamase was
      recognized by the yeast cell and the precursor protein was processed to an
      enzymatically active mature beta-lactamase. In contrast to conventional strains,
      the mutant strain was able to secrete bla-gene-encoded beta-lactamase into the
      culture broth. These results indicate the potential usefulness of ts1 mutant
      strains for biotechnological purposes.

PMID- 8310184
TI  - Bifidobacterial cell wall proteins (BIFOP) in Bifidobacterium globosum.
AB  - Nearly 150 strains of Bifidobacterium globosum were isolated from faeces of calf,
      chicken, lamb, rabbit and rat, from sewage, from rumen content and from human
      infant faeces between 1962 and 1973 and scored by SDS-PAGE for the presence of
      cell-wall-related proteins, i.e. BIFOP (bifid outer proteins); their apparent
      molecular masses ranged from 94.5 to 34 kDa and were designated A to L. Purified
      preparations from six of these ten proteins were employed to produce polyclonal
      rabbit antisera for use in immunoblots to investigate the interrelationships of
      the major antigens, A, B and C (94.5-85.5 kDa) and their distribution in strains
      of various origin. Two antigens differently migrating (or polymorphic forms)
      reacted with anti-BIFOP F serum (called F- and F+); the identity of BIFOP E with
      respect to these antigens was studied with anti-E serum. Only one antigen in all
      strain preparations reacted to anti-BIFOP H serum, which was raised against an
      antigen purified from a 13.5-MDa plasmid-bearing strain from rumen.

PMID- 8310185
TI  - A random effects model for ordinal responses from a crossover trial.

PMID- 8310186
TI  - Trees and tracking.
AB  - Epidemiologists have used the term 'tracking' to connote an individual's
      maintenance of relative rank of some longitudinally measured characteristic over
      a given time span. To assess the extent to which an attribute tracks we have
      first to summarize individual growth curves, and second to quantify the notion of
      maintenance of relative rank, both in the face of random error. A sequence of
      papers appearing in 1981 provided differing methodologies for appraising
      tracking. Here we take a different approach to tracking by using regression trees
      for longitudinal data. The above two concerns are simultaneously addressed in
      that the procedure identifies subgroups, defined in terms of covariates, within
      which the collection of growth curves is homogeneous. After reviewing the
      existing approaches to tracking we describe the tree-structured methodology, and
      present an illustrative example pertaining to lung function growth in children.

PMID- 8310187
TI  - A technique for summarizing longitudinal data.
AB  - Many studies collect longitudinal data but do not use them efficiently. We
      propose a technique for reducing a set of longitudinal data into four common
      summary statistics together with time. These statistics can be used in place of
      the raw data in further analyses, for example in a regression analysis. Instead
      of arbitrarily choosing the summary statistics, we derive them mathematically,
      thus justifying their use. This simplifies the subsequent analyses, and also
      improves the interpretation of the results. An example from the Framingham Heart
      Study illustrates the procedure.

PMID- 8310188
TI  - Bayesian analysis of binary data from an audit of cervical smears.
AB  - A large data set of unsatisfactory smear rates from 629 different cervical smear
      takers is used to illustrate a Bayesian approach to the analysis of medical audit
      data with a binary outcome. It is shown that this gives more relevant results in
      terms of characterizing individual smear takers than frequentist methods, and
      that the full Bayesian analysis is preferable to an empirical Bayes approximation
      when the number of different smear takers is small and at least one individual
      smear taker has contributed only a few smears. Plots of Bayesian posterior
      distributions with 95 per cent confidence sets are suggested as a useful way of
      feeding back the results to individual clinicians.

PMID- 8310189
TI  - How reliable are chance-corrected measures of agreement?
AB  - Chance-corrected measures of agreement are prone to exhibit paradoxical and
      counter-intuitive results when used as measures of reliability. It is
      demonstrated that these problems arise with Cohen's kappa as well as with
      Aickin's alpha. They are the consequence of an analogy to Simpson's paradox in
      mixed populations. It is further shown that chance-corrected measures of
      agreement may yield misleading values for binary ratings. It is concluded that
      improvements in the design and the analysis of reliability studies are a
      prerequisite for valid and pertinent results.

PMID- 8310190
TI  - Estimating kappa from binocular data and comparing marginal probabilities.
AB  - Suppose that two graders classify all eyes in a sample of patients for the
      presence or absence of a specified abnormality. In the statistical analysis of
      the data, possible correlation between the observations in the right and left
      eyes should be taken into account. Recently, general methods have been developed
      to analyse grader agreement in rating paired body structures. In the present
      paper, an alternative procedure is proposed that utilizes existing formulae for
      the computation of (weighted) kappa and its standard error. In addition, the
      McNemar test is generalized to compare the probabilities of a positive judgement
      by the two graders.

PMID- 8310191
TI  - Use of spending functions for occasional or continuous monitoring of data in
      clinical trials.
AB  - In many clinical trials, data are monitored periodically by an external data
      monitoring committee (DMC). Usually the frequency of these interim 'looks' at the
      data is prespecified. However, the progress of a clinical trial is unpredictable;
      often the schedule of looks must be modified. The Lan-DeMets procedure provides a
      spending function approach which does not require prespecification of the
      frequency or timing of interim looks. The procedure was developed based on the
      principle of a continuous Brownian motion process. In this paper we employ more
      elementary concepts to describe a procedure which is based upon the continuous
      monitoring of emerging data. The approach is flexible in that it applies to both
      continuous data monitoring and occasional interim monitoring. Examples are given
      from real clinical trials.

PMID- 8310192
TI  - Comparison of two tests useful in situations where treatment is expected to
      increase variability relative to controls.
AB  - The type I error and power characteristics of the modified t test were compared
      with those of the generalized t test. Results suggested that, in contrast to the
      generalized t test, the modified t test can be seriously non-robust to departures
      from population normality, with such departures often producing anti-conservative
      results. Neither test held an absolute power advantage over the other when
      responses were from normal distributions, but the modified t test was generally
      more powerful for these conditions. In comparison with the pooled samples t test,
      both tests were usually much more efficient when treatment caused increases both
      in mean response and between-subject variance, and suffered only small
      disadvantages when between-subject variance was unchanged by treatment. Given
      these results and other considerations, recommendations for use of these recently
      devised tests are given.

PMID- 8310193
TI  - The area between curves (ABC)--measure in nutritional anthropometry.

PMID- 8310194
TI  - Statistical handling of drop-outs in longitudinal clinical trials.

PMID- 8310195
TI  - [Current aspects of treatment of small-cell lung cancer].
AB  - Many combination regimens can induce a high response rate in patients with small
      cell lung cancer; however, the complete response rate is still modest and the
      median survival does not exceed one year in most studies, even in patients with
      limited disease. Chest radiation therapy improves the local controls and slightly
      prolongs survival in patients with limited disease, but long-term survival
      remains poor.

PMID- 8310196
TI  - [Paraneoplastic gastroparesis].
AB  - A 53-years-old woman with bilateral untreated breast cancer is admitted for
      intractable vomiting. No obstructive gastric disease is found but a marked
      delayed gastric emptying, suggesting the diagnosis of gastroparesis. No classical
      cause being demonstrated, the diagnosis of paraneoplastic gastroparesis is
      proposed. Treatment with cisapride and chemotherapy lead to regression of
      digestive symptoms and of breast tumor. This uncommon entity, usually described
      in association with small cell lung cancer, may involve the whole
      gastrointestinal tract, sometimes in association with abnormalities of the
      autonomous nervous system. Destruction of the myenteric plexuses by auto
      antibodies could be responsible for this pathology.

PMID- 8310197
TI  - [Is economic rational opposed to medical rational?].
AB  - Economic and medical rationalities could be conciliated. In a view of relative
      convergence various administrative decisions and new medicosurgical strategies
      are highlighted. The role of centres promoting continuous medical formation is
      stressed. They should also organize repetitive information campaigns.

PMID- 8310198
TI  - [History of general medical education].

PMID- 8310199
TI  - [Diabetic nephropathy: natural history and therapeutic interventions].

PMID- 8310200
TI  - [Hypertrophic obstructive myocardiopathy: surgical therapeutic options].

PMID- 8310201
TI  - [Focus on the classification, pathogenesis and current treatment of spondylolysis
      and spondylolisthesis].

PMID- 8310202
TI  - [Dermometric evaluation of edema of the lower limbs].

PMID- 8310203
TI  - Prevalence of rheumatoid arthritis in the adult Indian population.
AB  - The prevalence of rheumatoid arthritis was studied in the adult Indian
      population. As the first step, a house-to-house survey of a rural population near
      Delhi was conducted by two trained health workers. The target population
      comprised 44,551 adults (over 16 years old). The health workers identified the
      possible cases of rheumatoid arthritis (RA) using a questionnaire. These cases
      were then further evaluated by the authors using the 1987 revised ARA criteria
      for the diagnosis of RA. A response rate of 89.5% was obtained and 3393 persons
      were listed as possible cases of RA by the health workers. Of these, 299
      satisfied the revised ARA criteria for the diagnosis of RA, giving a prevalence
      of 0.75%. Projected to the whole population, this would give a total of about
      seven million patients in India. The prevalence of RA in India is quite similar
      to that reported from the developed countries. It is higher than that reported
      from China, Indonesia, Philippines and rural Africa. These findings are in
      keeping with the fact that the north Indian population is genetically closer to
      the Caucasians than to other ethnic groups.

PMID- 8310204
TI  - Influence of dichloromethylene diphosphonate on reactive oxygen species
      production by human neutrophils.
AB  - Biphosphonates suppress bone destruction in various diseases. Several studies
      have demonstrated the potential use of biphosphonate in arthritis. The results of
      these studies indicate that the effectiveness of the biphosphonates, for
      inhibiting the arthritic process, is related to their antiresorptive properties.
      It has been shown that the generation of reactive oxygen species is associated
      with the formation of new osteoclasts and enhanced bone resorption. We studied
      the effects of the dichloromethylene diphosphonate on the reactive oxygen species
      production by activated polymorphonuclear leucocytes, measured by
      chemiluminescence. Our results indicate a dose-dependent inhibitory effect of
      dichloromethylene diphosphonate on reactive oxygen species production by
      polymorphonuclear leucocytes stimulated with N-formil-methionyl-leucyl
      phenylalanine, the calcium ionophore A23187 and phorbol myristate acetate. The
      mechanisms by which this biphosphonate inhibits the reactive oxygen species
      production by activated polymorphonuclear leucocytes are discussed.

PMID- 8310205
TI  - Expression of the components and regulatory proteins of the alternative
      complement pathway and the membrane attack complex in normal and diseased
      synovium.
AB  - We have studied synthesis of the complement components and regulatory proteins of
      the alternative pathway and the membrane attack complex in synovial membrane. RNA
      was extracted from synovial tissue of patients with rheumatoid arthritis (RA) or
      osteoarthritis (OA) as well as from normal synovial membrane. Dot blot analysis
      showed the presence of mRNAs for all the complement components and regulatory
      proteins (C3, factor B, factor D, C5, C6, C7, C9, factor H, factor I, S-protein,
      SP-40, 40, DAF, MCP, CR1, CD59), except for properdin, C8 alpha, C8 beta and C8
      gamma in all three types of synovial membrane studied. In an attempt to determine
      which components were synthesised by each cell type, monocytes (mononuclear
      phagocytes), human umbilical vein endothelial cells (HUVEC), synovial membrane
      fibroblasts (from normal, OA and RA synovial membrane) and peripheral blood
      lymphocytes were cultured in vitro and secretion rates of individual components
      were measured and total cellular RNA analysed by northern blotting. Monocytes
      secreted properdin, C3, and factor H but not factor B, factor I, C5, C6, C7, C8
      or C9. Fibroblasts and endothelial cells secreted factor B, factor H and factor
      I, but not properdin, C5, C6, C7, C8 or C9. Lymphocytes did not secrete any of
      these components. mRNAs encoding C3, factor B, factor H, S-protein, SP-40, 40,
      MCP and DAF were detected in all three other cell types (monocytes, fibroblasts
      and HU-VEC), but factor I and CD59 mRNAs were not detected in monocytes. C5, C6,
      C7, C8 alpha, C8 beta, CD8 gamma and C9 mRNAs were not detected in any of the
      cell types studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8310206
TI  - The clinical significance of the detection of anti-Ro/SS-A and anti-La/SS-B
      autoantibodies using purified recombinant proteins in primary Sjogren's syndrome.
AB  - Recently, an enzyme-linked immunosorbent assay (ELISA), using purified
      recombinant non-fusion proteins, has been introduced to detect and quantify Ro/SS
      A and La/SS-B autoantibodies. We compared this method with anti-Ro/SS-A and anti
      La/SS-B detection by means of counterimmunoelectrophoresis and immunoblotting in
      patients with primary Sjogren's syndrome (SS), patients suspected of the syndrome
      and controls. The sensitivity and specificity of the newly developed ELISA for
      anti-Ro/SS-A were 53% and 100%, respectively, and for anti-La/SS-B, 40% and 98%,
      respectively. No significant difference was found between these results and those
      obtained from both other assays. Titres of Ro/SS-A and La/SS-B autoantibodies
      correlated with the presence of an abnormal parotid gland sialogram and
      hypergammaglobulinaemia. We concluded that the new ELISA did not enhance the
      diagnostic yield in cases of suspicion of primary Sjogren's syndrome.
      Longitudinal studies of large groups of patients with primary Sjogren's syndrome
      are necessary to demonstrate whether following the course of the titres of these
      autoantibodies would be of value for prediction of disease exacerbations.

PMID- 8310207
TI  - Abnormal T-cell function in patients with psoriatic arthritis: evidence for
      decreased interleukin 2 production.
AB  - Psoriatic arthritis (PSA) is an inflammatory arthritis associated with psoriasis.
      Although not considered an autoimmune process, there is evidence for humoral and
      cellular immune abnormalities similar to autoimmune diseases such as rheumatoid
      arthritis and systemic lupus (SLE). We investigated mitogen-induced proliferation
      and interleukin 2 (IL-2) production by peripheral blood mononuclear cells in
      patients with PSA. Both IL-2 production and proliferation were significantly
      decreased in PSA patients when compared to controls. Increased arachidonic acid
      metabolism has been reported in skin and peripheral mononuclear cells of patients
      with psoriasis and PSA. We therefore also investigated the effect of indomethacin
      and prostaglandin E2 (PGE2) on IL-2 production. Addition of indomethacin to
      cultures did not significantly change IL-2 production in patients with PSA, but
      did so in controls. PGE2 produced a significant reduction in IL-2 production in
      PSA and in controls.

PMID- 8310208
TI  - No direct correlation between HLA-DPB1 and antibodies against recombinant Ro (SS
      A)/La (SS-B) proteins in systemic lupus erythematosus. SLE Study Group.
AB  - We investigated the association of HLA-DPB1 alleles with the occurrence of
      autoantibodies against Ro (SS-A) or La (SS-B) using recombinant 52 kD-Ro, 60 kD
      Ro and La proteins in 177 German patients with systemic lupus erythematosus
      (SLE). A significant increase in the frequency of DPB1*0101 is observed in SLE
      patients compared to healthy controls (Pcorr.. < 0.004). Antibodies against 52 kD
      Ro, 60 kD-Ro and La are tested by ELISA and are found with a frequency of 25.4%,
      33.9% and 17.5% in the patients, respectively. An association with HLA-DPB1*0101
      is observed for antibodies against La (P < 0.01) and 52 kD-Ro (P < 0.01), but not
      for 60 kD-Ro in the absence of La/52 kD-Ro. Since there is a strong linkage
      disequilibrium between DPB1*0101 and DR3 in the normal population and in SLE
      patients, and since there is an association between DR3 and SLE, as well as
      between DR3 and the occurrence of recombinant Ro/La antibodies in SLE patients,
      we investigated whether DPB1*0101 is associated per se or via linkage
      disequilibrium with DR3. DPB1*0101 in the absence of DR3 is not more common in
      patients than in controls and not in patients with autoantibodies to Ro and La
      than without autoantibodies. We conclude that there is no evidence for a direct
      involvement of DPB1*0101 in the production of Ro/La autoantibodies in SLE
      patients.

PMID- 8310209
TI  - Subcutaneous edema: an "unrecognized" feature of acute polymyositis.
AB  - The case of a man with acute onset of muscle pain, weakness, anasarca, severe
      dysphagia and dysphonia, and biochemical, electromyographic and histologic
      evidence of polymyositis is presented. The literature on the occurrence of
      subcutaneous edema in polymyositis was reviewed. It is concluded that this
      particular symptom, with no other apparent cause, including heart failure from
      the underlying disease, is a rare but definite feature of polymyositis itself. A
      correlation of that with severe bulbar muscle involvement is also suggested.

PMID- 8310210
TI  - Failure of the serological determination of HLA-B27 due to antigen masking in
      patients with ankylosing spondylitis.
AB  - In patients suffering from ankylosing spondylitis (AS) HLA-B27 determination by
      means of the microlymphocytotoxicity test (MLCT) sometimes gives equivocal or
      false-negative results even though it has been performed with meticulous care.
      These failures of the test did not arise when the isolated mononuclear cells
      (MNC) were incubated in lymphocyte culture medium at 37 degrees C under sterile
      conditions for 24 h. To objectify these observations two methods of HLA class I
      typing were implemented before and after incubation of the test MNC in culture
      medium: a bioluminescence method based on the loss of adenosine triphosphate
      (ATP) in lysed cells in a modification of the usual MLCT and a flow cytometric
      (FC) test using direct immunofluorescence with an anti-HLA-B27 monoclonal
      antibody (MAB). In this study 50 patients with AS and 12 healthy volunteers were
      typed by the usual MLCT according to the NIH standard method and with both of the
      quantitative methods. In most of the AS patients the discrimination between
      positive and negative typing results became more distinct after 24 h incubation
      in culture medium. In the entire group of AS patients tested three false-negative
      typing results were prevented by this method. Although the MAB against HLA-B27 is
      cross-reactive with HLA-B7 and HLA-B22, errors in the FC analysis could be
      avoided by calibration of the flow cytometer with standard calibration beads.
      Possible explanations for masking of the HLA-B27 in AS patients are discussed.

PMID- 8310211
TI  - Primary antiphospholipid antibody syndrome and cerebral ischemia: report on acute
      intervention in two cases and literature review with emphasis on therapeutic
      options.
AB  - In two patients with primary antiphospholipid antibody syndrome and acute
      cerebrovascular ischemic events, local intraarterial fibrinolysis and intravenous
      heparin therapy, respectively, resulted in a limitation of persisting
      neurological deficits. On the basis of the 35 case reports available a
      combination of anticoagulation with warfarin, plus immunosuppression with
      steroids and/or cyclophosphamide or azathioprine, appears to be the best
      treatment to prevent further cerebral ischemic events. The therapeutic options
      are reviewed and discussed.

PMID- 8310212
TI  - [The eye, the optic system and its anomalies].
AB  - The eye is a perceptive system with extremely complex physiology, although its
      optical properties can be assimilated to those of spherical diopters. Various
      approximations make it possible to reduce the eyeball to a single convex diopter.
      With a normal eye the image of an object situated ad infinitum focuses on the
      retina. The normal eye is called emmetropic. Otherwise, the eye is called
      ametropic. Several types of ametropy exist. When the image focuses in front of
      the retina the eye is said to be myopic. When the image focuses behind the retina
      the eye is called hypermetropic (or hyperopic). When the image of an object
      differs according to various focusing axes, the eye is said to be astigmatic.

PMID- 8310213
TI  - [Refractive disorders. Clinical aspects and spontaneous course].
AB  - Refraction is the name given to determination of the dioptric values of the eyes,
      which is indispensable to correct the visual deficit due to ametropia. Disorders
      of refraction affect half the world population, and for this reason much
      attention should be paid to their diagnosis and treatment. Their various symptoms
      result in nuisances at school age and in the exercise of most professions,
      thereby preventing the subjects affected from enjoying a full life. Measuring
      refraction is a basic examination for all ophthalmologists.

PMID- 8310214
TI  - [Optic correction of myopia].
AB  - Correction of myopia by optics is still the most widely used method of visual
      rehabilitation. It raises visual acuity to levels that permit a normal life in a
      world where vision is particularly important. This success of glasses and lenses
      is most perfect for mild or moderate myopia. For subjects with severe myopia
      glasses are not without problems and contact lenses are preferable, but the
      results sometimes remain mediocre due to organic disorders resulting from
      excessive lengthening of the eyeball.

PMID- 8310215
TI  - [Severe myopia or myopia-disease?].
AB  - An increased axial length over 26 mm is one of the characteristics of highly
      myopic eyes. High myopia represents a marked type of the refraction disorders in
      which distance vision is impaired and leads to wear glasses in childhood. But
      this high myopia is also a degenerative myopia due to the distension of the whole
      envelopes of the ocular bulb mainly at the posterior part of it. Prevalence of
      high myopia in the general population ranges from 1 to 4%. The disease is usually
      inherited and transmitted in a dominant fashion. Degenerative myopic eyes are
      potentially blind eyes due to many complications occurring during lifetime at the
      choroidal or retinal level. Vision threatening retinal detachments are frequent
      and severe, and are sometimes related to a macular hole. Other diseases including
      glaucoma and cataract are more frequently encountered in those eyes but may be
      managed with higher success. Specific oculo-motor disturbances and strabismus are
      also encountered. At present, the main risk threatening central vision is macular
      disease with lacquer cracks and hemorrhages associated with subretinal new
      vessels growth. Only laser photocoagulation can halt the progression of the
      disease and avoid or delay severe loss of central vision.

PMID- 8310216
TI  - [The macula lutea in myopia].
AB  - High or degenerative myopia is associated to abnormalities of the posterior pole
      of the eye. Their expansion with time progresses to the occurrence of
      complications, especially neovascular ingrowth in the central macular area. The
      natural evolution of these new vessels results in loss of central vision at long
      term. Photocoagulation of the new vessels, sparing initially the center, has
      delayed the loss of central vision at 2 years in our randomized clinical trial.
      Only treated eyes retained useful acuity at 5 years. New therapeutic modalities
      will be possible when the mechanisms of occurrence of degenerative myopia are
      elucidated.

PMID- 8310217
TI  - [Myopia and rhegmatogenous retinal detachment].
AB  - There is a statistically significant correlation between rhegmatogenous retinal
      detachment and myopia. The prevalence of retinal detachment in myopic eyes is
      related to the prevalence of the disease precursors in such eyes. In most cases
      retinal detachments in myopic eyes share the clinical features of retinal
      detachments in emmetropic eyes. However, retinal detachments associated with
      giant tears and retinal detachment with atrophic holes in lattice, which are
      infrequent, show an increased prevalence in the myopic eye. In addition, retinal
      detachments associated with post-equatorial paravascular retinal tears, as well
      as retinal detachments with macular holes are specific or the myopic eye. Surgery
      is required in the management of retinal detachment. At present permanent retinal
      reattachment can be achieved in approximately 90% of eyes. The indications for
      prophylactic treatment remain debated. The high incidence of failures of
      prophylactic treatment is probably related to the limits of the current
      techniques.

PMID- 8310218
TI  - [Myopia and cataract].
AB  - Myopia and cataracts are frequently associated: a cataract may lead to index
      myopia; high myopia is complicated by the frequent and early development of
      cataracts. In this case, given the retinal fragility, there are problems in
      operating techniques and indication. Extra-capsular extraction with in-the-bag
      implantation is the safest technique. A lens implant of well-calculated strength
      can best correct a preexistent myopia. The refractive goal varies according to
      the patient's age and activity. Intra and postoperative complications are rarer
      than expected with such abnormal eyes. A useful visual acuity can be obtained in
      90% of the cases.

PMID- 8310219
TI  - [Surgery for severe myopia].
AB  - High myopia is such a major visual handicap that it justifies a search for
      surgical corrective methods to replace contact lenses when these can no longer be
      worn. However, the existing techniques meet, in their principle, with
      physiological and anatomical constraints which explains why none of these
      procedures can ensure predictable and stable results without significant risk of
      long-term complications. The methods used to modify the surface of the cornea and
      its power of refraction (corneal diopter) are keratomileusis and epikeratoplasty.
      The methods that act on the anterior segment and modify the overall dioptric
      power of the eye are myopic implants and clear lens surgery. All these procedures
      do is modify the refraction power of the myotic eye and suppress, or alleviate,
      the need for glasses or contact lenses. However, surgery does not protect against
      the mainly retinal complications of high myopia.

PMID- 8310220
TI  - [Surgery for moderate or mild myopia].
AB  - After a long period of hesitation and reluctance, surgery of moderate to mild
      myopia (1 to 6 dioptries) is currently practiced by specialists in refractive
      surgery. At present, two ambulatory techniques are in competition: radial
      keratotomy, a truly surgical procedure that is more than 10 years' old, and the
      much more recent photorefractive keratectomy performed with an excimer laser
      beam, which is still under evaluation but has a very promising future. The goal
      of these two techniques is to correct myopia by flattening the cornea. The degree
      of correction obtained depends on several variables (some of which can be
      mastered), which explains why the results are not fully predictable. However, the
      overall results are satisfactory, provided the indications have been strictly
      selected. Per- and postoperatory complications are extremely rare. The main risk
      is early under-correction (particularly when the initial myopia is pronounced) or
      late over correction, mainly observed with radial keratotomy. Visual
      rehabilitation is much slower with the laser technique than after radial
      keratotomy. The two techniques are applied to patients aged from 20 to 40 years
      who have stable myopia, do not tolerate contact lenses and need an excellent
      sight for their professional or sporting activities.

PMID- 8310221
TI  - [Hypermetropia].
AB  - Hypermetropia, like myopia, is a defect of axial refraction, most often due to
      reduction of the anteroposterior diameter of the eyeball. Hypermetropia is normal
      in the young child and usually diminishes with age. Moderate hypermetropia is
      generally well tolerated in young subjects. When severe or associated with
      functional changes, hypermetropia should be corrected by prescription lenses.
      Contrary to myopia, definitive treatment by surgery is not yet current practice
      in hypermetropia.

PMID- 8310222
TI  - [Astigmatism and its treatments].
AB  - Astigmatism is a refractive error related to corneal asphericity. Congenital
      astigmatism is most frequent, and its correction with spectacles has been known
      for a long time. Contact lenses may sometimes be useful, but they may not allow a
      satisfactory visual correction. Anterior segment surgery (cataract, penetrating
      keratopasty, etc.) may often cause postoperative astigmatism. Improvement in
      ophthalmic surgery, and the patient's need for a rapid and effective visual
      recovery (as anatomical result is obtained), have highlighted prevention and
      treatment of post-surgical astigmatism. Astigmatism treatment is complex and
      varies according to its intensity and cause. Refractive surgery, modifying
      corneal shape, may be an elegant solution in cases where vision is low, in spite
      of a perfect corneal transparency.

PMID- 8310223
TI  - [Presbytia: are eyeglasses unavoidable?].
AB  - The power of eye accommodation to close vision decreases with age. This
      physiological process, called presbytia (or presbyopia), occurs in all people
      reaching maturity, irrespective of sex and race. This paper describes the
      evolution of our knowledge concerning this phenomenon and the various means of
      correction utilized nowadays to compensate for the loss of accommodation power.

PMID- 8310224
TI  - [Factors of resistance to the treatment of hypertension. They are multiple, but
      often controllable, without therapeutic escalation].

PMID- 8310225
TI  - [Can cerebrovascular complications occur before birth?].

PMID- 8310226
TI  - [Prognosis and follow-up of neurogenic bladders. The essential contribution of
      urodynamics].

PMID- 8310227
TI  - [Prevention of recurrence of duodenal ulcer by eradication of Helicobacter
      pylori. A major progress].

PMID- 8310228
TI  - [Fluoroquinolones, 10 years later].
AB  - During the last few years the fluoroquinolone class has been profoundly reshaped.
      The development of mutation-acquired resistance, principally from staphylococci
      and Gram-negative bacteria responsible for nosocomial infections has restricted
      the use of these antibiotics as first-line monotherapy to some community-acquired
      infections (urinary tract, gastrointestinal, sexually transmitted infections),
      while defects in their antibacterial spectrum (pneumococci, streptococci and
      anaerobes) have reduced the possibility of use against respiratory infections.
      Future developments concern compounds that are active against Gram-positive cocci
      and some intracellular bacteria (e.g. mycobacteria) and possibly against certain
      parasites. Problems of tolerance are important in clinical trials of the new
      compounds.

PMID- 8310229
TI  - [Horton disease. Pathological anatomy].

PMID- 8310230
TI  - [Rheumatoid arthritis. Pathological anatomy].

PMID- 8310231
TI  - [Hodgkin disease. Pathological anatomy].

PMID- 8310232
TI  - [The concept of specific inflammation: lymph node tuberculosis. Pathological
      anatomy].

PMID- 8310233
TI  - [Hepatitis A, B, C and D. Pathological anatomy].

PMID- 8310234
TI  - [Non-cirrhotic alcoholic liver diseases. Pathological anatomy].

PMID- 8310235
TI  - [Alcoholic cirrhosis. Pathological anatomy].

PMID- 8310236
TI  - [Colon cancer. Pathological anatomy].

PMID- 8310237
TI  - [Rectal cancer. Pathological anatomy].

PMID- 8310238
TI  - [Acute appendicitis. Pathological anatomy].

PMID- 8310239
TI  - [Primary broncho-pulmonary cancers. Pathological anatomy].

PMID- 8310240
TI  - [Thyroid cancers. Pathological anatomy].

PMID- 8310241
TI  - [Psychosocial determinants of massive obesity].
AB  - Subjected to the reversed relationship between corpulence and socio-cultural
      level, massive obesity is, in Western countries, more frequent in the lowest
      social classes, and particularly in women. The influence on bodyweight of
      restricted food intake, physical activity and relative proportion of fats in
      daily diet has been demonstrated, and these 3 interacting factors vary with the
      social class. Although they are unanimously blamed for their enormous weight,
      subjects with massive obesity do not have a higher psychopathological index than
      other obese subjects or people with normal weight. On the other hand, the search
      of these massively obese subjects for a hypernormal presentation to compensate
      for the "abnormality" of their physical appearance (partially dependent on
      genetic factors) leads them to deny a great deal of the emotional and nutritional
      reality. This denial, overlooked by health institutions, could have been full of
      consequences. By generating wrong evaluations it would have contributed to the
      inadequacy of therapeutic responses which in turn would have made the obesity
      worse. Taking into account this phenomenon should improve the adequacy of
      therapeutic strategies and hence the prognosis.

PMID- 8310242
TI  - [Definition and epidemiology of massive obesity].
AB  - Massive obesity is defined by a body mass index [weight (kg)/height (m)2] greater
      than 40. It corresponds to an increase in mortality ratio. Its frequency differs
      among countries and its incidence is important in USA (13 million subjects),
      Finland, and South Africa. Obesity is now a serious, emerging problem in
      developing countries. Frequency of obesity is influenced by age, sex, race and
      has increased during the last 30 years. Importance of heredity has been
      highlighted. Recently an increase in superobesity in childhood has been observed,
      especially in the United States. Finally, besides people with stable obesity
      throughout their life, there are subjects with weight cycling. These subjects
      have higher cardio-vascular risks than the others.

PMID- 8310243
TI  - [Handicaps of massive obesity].
AB  - Massive obesity results in psychological--internal, relational, behavioural and
      psychosocial--handicaps due, to a great extent, to a society which encourages the
      occurrence of obesity but does not tolerate those who present with this
      condition. As the weight increases, the quality of life diminishes. Moreover, the
      mental performances of very obese individuals seem to be inferior to those of
      subjects with normal weight. Treatments which include a restrictive diet are the
      sources of depressive symptoms related to the chronic restriction. So far, only
      those patients who were operated upon, and particularly those who underwent
      gastroplasty, enjoy a dramatic improvement in their quality of life. As for those
      massively obese subjects who are not concerned with this solution, long-term
      supporting measures should be developed.

PMID- 8310244
TI  - [Respiratory function in massive obesity].
AB  - Massive obesity may be accompanied by severe and sometimes lethal respiratory
      complications. The restrictive ventilatory deficit which results from a decrease
      in thoracic wall compliance and perhaps also from diaphragmatic dysfunction is
      more severe in males and in subjects with abdominal obesity. Diurnal hypoxaemia
      results from 2 mechanisms: diminution of the ventilation/perfusion ratio at the
      base of the lung, and alveolar hypoventilation. Hypercapnia is a fairly frequent
      complication of massive obesity. Although usually moderate, hypercapnia is a
      major indicator as it is very often associated with sleep apnoea syndrome. The
      most severe respiratory complication of massive obesity is this syndrome which
      must be looked for systematically by questioning the patient and her husband or
      his wife before serious cardiopulmonary and neuropsychic disorders appear. The
      effects of weight loss of nocturnal apnoea are inconsistent and variable.
      Continuous positive pressure ventilation by means of a nasal mask is the choice
      treatment of sleep apnoea syndrome, especially since the results of rhino
      laryngeal surgery are often disappointing.

PMID- 8310245
TI  - [Hemodynamics of massive obesity].
AB  - Congestive heart failure is a frequent complication of massive obesity and a
      major cause of death. Prior to the cardiac decompensation stage, infraclinical
      haemodynamic disturbances can be observed in obese subjects with normal blood
      pressure: the cardiac output and cardiac index increase, due to a rise in
      systolic ejection volume, the total peripheral resistance falls and the
      intravascular volume augments. Cardiac adjustment takes place in the form of
      excentric left ventricular hypertrophy. Ventricular extrasystoles, often
      associated with this hypertrophy, might be the cause of sudden death in some
      obese patients. Arterial hypertension is about 3 times more frequent in obese
      subjects than in subjects of normal weight, and even more frequent in those with
      massive obesity. To the high preload due to obesity hypertension adds an
      increased after-load. This results in augmentation of the mass and work of the
      left ventricle with progressive alteration of its function. The incidence of
      coronary disease is increased in obese subjects, notably those with abnormal
      adiposity. Finally, the return circulation is very often perturbed, notably in
      gynecoid obesity: there is venous insufficiency with a higher risk for
      thromboembolism, and lymphatic insufficiency or capillary permeability disorders.
      A low-calorie diet and a physical rehabilitation of sedentary obese subjects
      facilitate weight reduction and at the same time tend to correct the associated
      metabolic disturbances; they reduce blood pressure and also seem to reduce the
      left ventricular hypertrophy.

PMID- 8310246
TI  - [Osteoarticular pathology and massive obesity].
AB  - Rheumatic symptoms are often associated with obesity. The usual symptom is pain
      in the knee due to gonarthrosis, of which one of the causes is obesity; there is
      a correlation between the degree of overweight and the severity of gonarthrosis.
      It is likely, though not demonstrated, that overweight aggravates the arthrosis
      of supporting joints. On the other hand, obesity limits the post-menopausal bone
      loss. The intestinal bypass created to obtain a loss of weight may generate
      complications, and in particular an inflammatory rheumatism due to proliferation
      of bacteria in a blind intestinal loop, and osteomalacia caused by disorders of
      vitamin D absorption sometimes develops. The risk of perioperative complications
      is increased in obese patients. The mid-term results of hip or knee surgical
      replacement seem to be good. In the present state of our knowledge, its seems to
      be rational to convince obese patients complaining of rheumatic illness that they
      should lose weight.

PMID- 8310247
TI  - [Cutaneous complications of massive obesity].
AB  - Massive obesity leads to nonspecific skin disorders. Skin folds are more numerous
      and deeper in the obese subject, and can become the site of various disorders.
      Hence the difficulty of diagnosis and treatment is increased. Acanthosis
      nigricans should be recognized, but not solely attributed to obesity, since other
      causes, particularly cancer, may be involved. Finally, leg ulcerations, a
      frequent consequence of the venous insufficiency inherent in obesity, should not
      lead to overlook other underlying causes, particularly in diabetic patients.

PMID- 8310248
TI  - [Endocrine and metabolic consequences of massive obesity].
AB  - Massive obesity is always accompanied by insulin resistance with
      hyperinsulinaemia in proportion to the amount of visceral fat, which has
      repercussions on oxidative and non-oxidative glucose metabolism. The increase of
      free fatty acids in direct relation to the adipocytic mass reduces the hepatic
      insulin uptake; it increases the suprahepatic glucose flow and the production of
      very low density lipoproteins. The adipose tissue exerts a feminizing effect in
      men and a masculinizing effect in women. Women have disorders of ovulation and
      hirsutism, with increase of free testosterone and elevation of luteotropic
      hormone levels. Men have hypoandrism due to excessive aromatization of androgens
      and oestrogens. The adipose tissue accelerates the turnover of cortisol and
      facilitates cortisone production, which stimulates ACTH secretion and maintains
      stimulation of the adrenal cortex. Hyperinsulinism and resistance to insulin also
      intervene in hormonal regulation. They elevate the insulin-like growth factor 1
      (IGF-1) which inhibits the production of growth hormone and reduces its plasma
      half-life; hyperinsulinism and IGF-1 facilitate ovarian androgen production;
      hypothalamic disturbances occur by diminution of sensitivity to hypoglycaemia,
      and there are abnormalities in monoaminergic and serotoninergic control. Bone
      tissue density is preserved for a long time, as it is in proportion to the fatty
      mass and to the oestrogen and IGF-1 levels, but it may be gradually reduced by
      secondary hyperparathyroidism. Thyroid function and thyrotropic regulations are
      unaffected.

PMID- 8310249
TI  - [Nephropathy of massive obesity].
AB  - Glomerular proteinuria without significant functional disorders or histological
      lesions can be found in massively obese patients. Nephrotic syndrome, segmental
      hyalinization of the glomeruli and altered filtration are exceptional. In most
      cases, therefore, glomerular proteinuria requires only supervision without
      treatment. The physiopathogenesis of this nephropathy (renal vein hyperpressure?)
      has not yet been fully elucidated.

PMID- 8310250
TI  - [Treatments of massive obesity].
AB  - Treatment of massive obesity aims at somatic, psychological and social targets
      and therefore requires a multidisciplinary team co-ordinated by a physician.
      Treatment usually begins by taking care of the most worrying somatic and
      metabolic problems (cardio-respiratory and metabolic disorders) and by correcting
      the diet. It is then enhanced by a psychological assistance provided by the
      treating team and, in certain cases, by a psychotherapist. Massive obesity is a
      chronic, recurrent and severe disease. Its treatment is prolonged and implies
      numerous constraints (diet, drugs, treatment of a possible sleep apnoea syndrome)
      which are difficult to tolerate in the long term. This type of management
      resembles that of other chronic diseases, such as complicated diabetes. From
      dietetics to the most technical medicine, from the doctor-patient relationship to
      psychotherapy, the therapeutic methods are numerous, and the burden of using them
      in a coherent manner falls on the physician.

PMID- 8310251
TI  - [Massive obesity and anesthesia].
AB  - Obese subjects are at a high risk of cardiovascular, respiratory and
      thromboembolic diseases. Anaesthetists in charge of these patients must take this
      risk into account, along with technical problems such as difficult venous
      punctures and intubations. The supine position alone creates situations that can
      be catastrophic for the respiratory and cardiac functions. In addition, obesity
      may modify the pharmacokinetics of the often liposoluble drugs used in
      anaesthesia. From the preoperative to the postoperative phases the anaesthetist's
      intervention must be envisaged.

PMID- 8310252
TI  - [Can atypical mycobacteria infections be treated? Diversity and complexity].

PMID- 8310253
TI  - [Glanzmann's thrombasthenia. A rare but exemplary disease].

PMID- 8310254
TI  - [Fatigue fractures].
AB  - Stress fractures are extremely common microtraumatic lesions which occur in
      specific areas of healthy bones. Since clinical findings are often misleading and
      radiological signs are known to be delayed, diagnosis can be uneasy. In some
      instances, infectious or tumoral diseases have to be ruled out. Such difficult
      cases are shown to stress on the potential interest of CT scanner and magnetic
      resonance imaging.

PMID- 8310255
TI  - [Hypertension and pregnancy: physiopathology, treatment, prevention].
AB  - Pathophysiologic understanding of the hypertensive diseases of pregnancy has
      largely progressed in the past 10 years. The key phenomenon is an early defect of
      placentation, occurring at the end of first trimester. It is associated with a
      more global endothelial disorder. This results in early activation of
      coagulation, and an imbalance between prostacyclin and thromboxanes. Hypertension
      and proteinuria only occur after several weeks or months of placental
      dysfunction. This explains why antihypertensive treatments are ineffective in
      improving the prognosis of such pregnancies. On the contrary, early preventive
      treatments, such as antiplatelet therapy, seem very promising for those patients.

PMID- 8310256
TI  - [Diplopia. Diagnostic orientation].

PMID- 8310257
TI  - [Pleural effusion. Diagnostic orientation].

PMID- 8310258
TI  - [Sympatholytics. Principles and rules of use].

PMID- 8310259
TI  - [Angina pectoris. Epidemiology, etiology, physiopathology, diagnosis, course,
      treatment].

PMID- 8310260
TI  - [Traumatic rupture of the urethra. Diagnosis and emergency treatment].

PMID- 8310261
TI  - [Non-tuberculous acute salpingitis. Etiology, diagnosis, course, prognosis,
      treatment].

PMID- 8310262
TI  - [Hepatomegaly. Diagnostic orientation].

PMID- 8310263
TI  - Studies on mosquitoes (Diptera: Culicidae) and anthropic environment. 1--Parity
      of blood seeking Anopheles (Kerteszia) in south-eastern Brazil.
AB  - Populations of Anopheles (Kerteszia) were sampled fortnightly over a one-year
      period (August 1991 to July 1992) at Ribeira Valley, S. Paulo State, Brazil.
      Indoor and outdoor collections were made on human bait at evening crepuscular
      period. The Polovodova technique for age grading was applied to 3,501 females of
      Anopheles cruzii and to 416 females of An. bellator. That sample represented
      34.4% of the total number of mosquitoes collected. The most abundant species
      found was An. cruzii. However, An. bellator showed an endophagy that was almost
      three times greater than that of An. cruzii. The overall parous rate was 25.4%
      and uniparity was practically dominant one. A proportion of 26.9% of An. cruzii
      and 12.0% of An. bellator were found to be uniparous. Only three outdoor females
      of the former species (0.1%) showed biparity. Parity of An. cruzii was higher in
      females caught indoors than in those caught outdoors. Nevertheless, 497
      nulliparous females examined (417 cruzii and 80 bellator) had ovaries that had
      advanced to Christophers and Mer stages III to V. These results imply that these
      females had already practised hematophagy. Relating these results to those from
      the parous females, a high statistical significance was found, leading to the
      conclusion that gonothophic discordance is a common pattern among these
      anophelines. Further, these results obtained with human bait catches strongly
      suggest that nearly 38.0% of these host-seeking females had already taken at
      least one previous blood-meal. So it is possible that enough time could thus be
      available for the plasmodian development in the vectors.

PMID- 8310264
TI  - [Myocardial infarct and cerebral vascular disorders associated with high
      temperature and carbon monoxide in a metropolitan area of southeastern Brazil].
AB  - Many studies have been published about the relationship between life style and
      genetic risk factors and stroke and heart attack, but there have been few about
      the relationship between atmospheric pollution, specifically with carbon
      monoxide, and temperature and stroke and heart attack. With a view to filling
      this gap the relationship between values of carbon monoxide concentration in the
      air, maximum and average by day, and maximum temperature by day and the number of
      new cases of CVA and IM admitted as emergencies at the biggest hospital complex
      of S. Paulo city was analysed. If was concluded, by the use of multivariable
      regression analysis, that 2.1% and 4.9% of heart attack admissions were due to
      carbon monoxide air pollution and high temperature, respectively. 2.8% of stroke
      admissions were due high temperature. Stroke and carbon monoxide were not
      associated in this population.

PMID- 8310265
TI  - [Prevalence of alcoholic beverage consumption and alcoholism in a metropolitan
      region of Brazil].
AB  - An epidemiological survey was carried out for the purpose of estimating the use
      of psycho-active substances and the prevalence of alcoholism. The target
      population consisted of people over 13 years old living in a district of Rio de
      Janeiro city-Brazil. A random sample of 1,459 people was researched. Data on the
      use of alcohol and on alcoholism are presented. The diagnosis of this latter,
      based upon the CAGE Test, showed that 51% used alcohol and 3% were suspected of
      alcoholism: 4.9% and 1.7% among men and women, respectively. The greatest
      prevalence of the use of alcohol and of alcoholism was found among men between 30
      and 49 years of age. Abstinence from alcohol was more frequent among widowed,
      Evangelical and low-income groups.

PMID- 8310266
TI  - [Influence of migration on the prevalence of serologic hepatitis B markers in a
      rural community. 1. Analysis of prevalence by birthplace].
AB  - Distribution of hepatitis B serological markers according to people's birthplaces
      and area of residence (urban/rural) was studied as a part of a field
      epidemiological research project carried out in Cassia dos Coqueiros, a small
      rural community of S. Paulo State, Brazil. The total prevalence of HBV markers
      was 7.7%, with rural showing a higher risk than urban inhabitants (9.8% as
      against 4.9%, respectively). Analysis of prevalence according to people's
      birthplaces revealed the highest value among those from other Brazilian states
      (15.8%), followed by people from other municipalities of the State of S. Paulo
      (9.2%). Those born in Cassia dos Coqueiros and particularly in Ribeirao Preto
      (the main city of the area, located 80 kilometers away), showed the lowest values
      of prevalence (5.2% and 2.5%, respectively). The importance of studying people's
      birthplaces when field epidemiological studies on hepatitis B are carried out is
      stressed. This variable is considered to be capable of exercising an influence on
      the natural history of the disease in a community, and may even explain
      differences in the distribution of markers in apparently similar populations.

PMID- 8310267
TI  - [Influence of migration on the prevalence of serologic hepatitis B markers in a
      rural community. 2. Comparative analysis of various characteristics of the
      population studied].
AB  - The association between prevalence of hepatitis B serological markers and
      birthplace, in a study carried out in a small rural county of S. Paulo State,
      Brazil, suggests different risk factors for hepatitis B between migrants and
      nonmigrant populations. These two groups were compared with regard to the
      following variables: level of education, professional occupation, number of
      previous hospitalizations, past history of blood transfusions and type of dental
      treatment. Migrants, mainly those from other states of Brazil, showed a low-level
      of education, a high proportion of people employed in agricultural activities, a
      higher number of past hospitalizations and higher exposure to blood transfusion
      and to more aggressive dental procedures. Associations were observed between the
      prevalence of serological markers and the following variables: level of
      education, professional occupation, number of previous hospitalizations and type
      of dental procedures, even though the last two associations did not justify the
      higher prevalences observed among migrants. The different distribution of
      hepatitis B markers seems to be dependent on the migrants' worse socio-economic
      condition, demonstrated by their lower level of education and by the predominance
      of secondary occupations.

PMID- 8310268
TI  - [Risk factors for non-communicable diseases in a metropolitan area in the south
      of Brazil. Prevalence and simultaneity].
AB  - Three-quarters of deaths in Rio Grande do Sul State, Brazil, are due to non
      communicable diseases-cardiovascular diseases, alone, being responsible for 35%
      of them. To evaluate the prevalence of risk factors for these diseases, a
      household survey of 1,157 randomly sampled individuals between 15 and 64 years of
      age was undertaken in 1986 and 1987 in census tracts of 4 areas of the city of
      Porto Alegre. The age- and sex-adjusted prevalence of smoking was 40%,
      hypertension 14%, obesity 18%, overall sedentary life-style 47%, and excessive
      alcohol consumption 7%. Thirty-nine percent of the sample presented two or more
      of these five risk factors, and only 22% of men and 21% of women had none of
      them. The high frequencies and simultaneous presence of these risk factors
      indicate their importance for programs aimed at the prevention of non
      communicable diseases and the promotion of adult health.

PMID- 8310269
TI  - [Factors associated with prenatal care among low income women in the State of Sao
      Paulo, Brazil].
AB  - This paper presents the results of a study carried out in 1988 in the State of S.
      Paulo, with the purpose of evaluating the Program for Women's Integral Health
      Care. A total of 3.703 low income women of 15-49 years of age were interviewed
      using a structured, pre-tested form. The data in this paper relate to 669 women
      who had been pregnant during 1987 or 1988 and who were asked about pre-natal,
      delivery and post-partum care. The association between some of their socio
      demographic characteristics and the pre-natal care received, months pregnant at
      the time of first visit and total number of visits, were analysed. Results showed
      an association between socio-economic characteristics and pre-natal care
      received. The greatest percentage of pregnant women who had had pre-natal care
      was found among those with more than elementary education. The highest percentage
      of women who started prenatal care before the third month of pregnancy was found
      among those who had no living children (74%), were in union (70%), had at least
      some high school education (88%) and lived in the interior of the state (71%).
      The results show that it is necessary to increase the coverage and quality of pre
      natal care so as to improve perinatal results.

PMID- 8310270
TI  - [Sickle cell disease as a public health problem in Brazil].
AB  - Sickle cell anemia is the most prevalent hereditary disease in Brazil. However,
      the Brazilian literature registers no investigations into the public health
      aspects of the disease. This present study investigates the way of life of 80
      adult patients (49 women and 31 men) with a diagnosis of sickle cell anemia, at a
      blood center in Brazil. The late diagnosis of the disease was one of the most
      significant aspects observed in this group of patients. It was also observed that
      the dominant problem faced by adult patients with sickle cell anemia is of an
      economic nature, mainly due to lack of professional opportunities. However,
      patients can well undertake economic activities under adequate medical
      supervision, according to their own limitations and potentialities. The
      psychotherapeutic orientation was well accepted by patients regardless of sex. It
      is concluded that there exists need for the establishment of community programs
      for early diagnosis and medical, social and psychological orientation for sickle
      cell anemia patients in Brazil.

PMID- 8310271
TI  - [Heavy metal and organochlorine pesticide blood levels in children of 1 to 10
      years of age].
AB  - A study of a sample of 251 children aged between 1 and 10 was carried out in 6
      districts of Cubatao county, S. Paulo State, Brazil. This study showed the
      presence of organochlorine pesticides in the blood serum of 242 children. p-p'
      DDE was detected in 73 of the samples (30%) and HCH in 47 of them (19%). The mean
      value of p-p' DDE was 0.85 +/- 2.13 micrograms/l. and that of HCH was 0.28 +/-
      0.79 micrograms/l. Lead and mercury were also detected in the blood serum. The
      mean value for lead was 17.8 +/- 5.8 micrograms/l. and for mercury was 9.1 +/-
      0.79 micrograms/l. The levels found in consumers of aquatic organisms taken from
      the rivers of Cubatao showed a mean mercury level (mean = 14.7 +/- 7.1
      micrograms/l.) higher than (p < 0.04) that of those who did not consume any
      aquatic organisms at all (mean = 10.0 +/- 6.5 micrograms/l.).

PMID- 8310272
TI  - [Cancer in the female population in Brazil].
AB  - This study seeks to show the importance of cancer as a cause of morbidity and
      mortality among Brazilian women. Mortality data from the Health Ministry and
      incidence data from the six Brazilian Population Based Cancer Registries (Belem,
      Fortaleza, Recife, S. Paulo, Porto Alegre e Goiania) were used. Cancer accounted
      for 15.5% of all deaths in women above fifteen years of age, in 1986. Breast and
      uterine cancer were responsible for some 30% of these deaths. International
      comparisons show that Recife and Belem had the highest incidence rates from
      cervical cancer in the world. The incidence of breast cancer in Porto Alegre, S.
      Paulo, Fortaleza and Goiania approximated to the figures for regions of high
      incidence such as the United States and some European countries. Risk factors in
      leading female cancers are discussed in the light of cultural, social and
      geographical differences, as well as the development of screening programs. It is
      concluded that screening and early-detection programs for cervical and breast
      cancer had very low coverage in the country. The insertion of actions for the
      prevention and early diagnosis of cervical and breast cancers in women's health
      care programs should be considered one of the priorities for public health in
      Brazil.

PMID- 8310273
TI  - [Outbreak of malaria induced among users of injectable drugs].
AB  - Five cases of malaria were detected among cocaine users by the local health
      service in Bauru, a city with a population of 260,000, located 324 km from S.
      Paulo, Brazil, during the first three weeks of July 1990. Autochthonous malaria
      had not occurred in Bauru since 1978, and all the five cases denied having
      recently traveled to endemic areas. An extensive epidemiologic survey conducted
      from July 19 to September 13 revealed that the 5 cases were in fact part of a
      malaria outbreak among endovenous drug users. Moreover, at least 114 other
      people, who had in the last three months shared syringes and needles with one or
      more proved cases, were also involved in the outbreak. One hundred and two people
      were identified and interviewed orally. The examination of thick smears made from
      samples collected from 99 of them confirmed 21 cases of vivax malaria. Three
      people with negative blood smears had an indirect immunofluorescent assay
      positive to P. vivax antigen. Although the index case could not be discovered,
      the investigation suggested that one or more people who had recently traveled to
      the Amazon region might have introduced the disease. The control of the outbreak
      was achieved after offering treatment with chloroquine (10 tablets) to confirmed
      cases and contacts, followed by weekly suppressive chloroquine (2 tablets) until
      the last contact was detected. Malaria examination of 91 blood samples also
      revealed a high prevalence of hepatitis B virus infection (40%) and HIV infection
      (58%) among those involved in the outbreak. The strategy used to identify the
      cases and the contacts and the difficulties overcome in carrying it through are
      described.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8310274
TI  - Elderly women in the Nordic countries; level of living and situation in life.
AB  - A joint Nordic research project aiming to obtain more knowledge about the
      situation of elderly women, has been funded by the Nordic Council of Ministers
      and the authorities in each participating country (Denmark, Finland, Iceland,
      Norway and Sweden). In essence and practice, the project is testing to what
      extent gender is a fruitful element in gerontological research, and whether high
      age as a topic can contribute to a better understanding of women's situation. In
      other words, the project integrates two academic traditions; feminist research
      and gerontological research, thus creating feminist gerontology as a field of
      study. Analysing the data of Nordic level of living surveys, the research group
      studies the variations in "Norden" in the situation regarding of elderly women
      the following topics: family pattern, resources of social contact and care,
      morbidity and infirmity, education, work, material and economic resources and
      fear of violence. The study also includes a description of the demographic
      development in "Norden".

PMID- 8310275
TI  - Summarization, smoothing, and inference in epidemiologic analysis. 1991 Ipsen
      Lecture, Hindsgavl, Denmark.
AB  - In a recent article (Epidemiology 1990; 1: 421-429) I resurrected some historical
      criticisms of conventional statistics in non-randomized, non-randomly sampled
      studies, and suggested some improvements to current practice in response to these
      criticisms. Here, I propose that some resolution can be achieved by separating
      data analysis into summarization, smoothing, and inferential phases. Methods of
      statistical inference are in fact smoothing methods, as are many methods of
      descriptive statistics, and as such can be viewed as pattern-recognition devices.
      Scientific inference is not a statistical process, but instead concerns
      derivation of explanations for patterns detected by statistical methods.
      Improvements could be made to all three phases simply by keeping the phases
      distinct.

PMID- 8310276
TI  - Construct validation and the Rasch model: functional ability of healthy elderly
      people.
AB  - The purpose of this study was to test the construct validity of a measure of
      functional ability, developed with the intention of achieving a high degree of
      variability and capacity for discriminating among a group of healthy elderly
      people. Data were collected from 734 70-year-old people in Denmark in the county
      of Copenhagen. Functional ability was measured with the traditional activities of
      daily living and with a classification system developed specially for healthy
      elderly people. Construct validity was tested by the Rasch model for item
      analysis, addressing specifically the internal validity by assessing the
      homogeneity of items under different conditions. The results show that the
      proposed measure of functional ability is a combination of six different
      dimensions, divided into 3 types: mobility function, lower limb function and
      upper limb function. With regard to these three types decreased functional
      ability can appear by either tiredness or reduced speed.

PMID- 8310277
TI  - Abuse is in the eye of the beholder. Report by family members about abuse of
      demented persons in home care. A total population-based study.
AB  - In a population-based study 219 family members of cognitively impaired elderly
      (casegroup) and 255 family members of cognitively healthy elderly (control-group)
      were interviewed about their situation as a caregiver to an old person. Twenty
      six family members in the case-group reported abusive behavior in the care of the
      elderly at home. These family members are compared with 154 family members in the
      control-group, reporting other coping strategies than abusive. In the abusive
      group most of the elderly were in a mild stage of dementia, and the family
      members reported more strain in the care situation. The family members were
      older, judged their health as deteriorated, and were mostly living together with
      the dependent elderly.

PMID- 8310278
TI  - Perceived functional health of frail elderly in a primary home care programme and
      correlation of self-perception with objective measurements.
AB  - This study examined the effects of a primary home care intervention programme on
      self-assessed functional health, and the correlation of self-perception with
      objective measures in frail elderly subjects. Elderly patients about to be
      discharged from an acute hospital, at risk for institutionalization, were
      randomly assigned to physician-led primary home care or to standard care. After
      early post-hospital in-home intervention and assessment, ongoing medical care and
      treatment were monitored by a multidisciplinary team. Functional data were
      collected at baseline and after six months. Self-rated and objectively rated
      functional variables included medical factors, personal and instrumental
      activities of daily living, ambulation, and social activities and contacts. From
      study entry to follow-up, the scores for personal activities of daily living were
      significantly increased in team and control subjects as were social contacts in
      the team subjects (P = 0.03). No differences between team and control groups were
      found for self-rated functions from study entry to follow-up, except for a
      tentatively statistical significance in self-rated physical health in favour of
      the team subjects. Positive correlations were recorded between all self-rated and
      objectively rated functions, but they were stronger at follow-up. Physical health
      and social contacts were overrated, whereas indoor ambulation and social
      activities were underrated compared to objective measures at follow-up. Personal
      activities of daily living, were overrated at study entry, but showed substantial
      agreement at follow-up (0.62). Within demographic subgroups patients over 80
      showed a stronger correlation between self-rated and objectively measured social
      functions after six months than younger patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8310279
TI  - Medications and chronic diseases as risk factors for falling injuries in the
      elderly.
AB  - Diseases and medications associated with the occurrence of falls leading to
      medical treatment in elderly Finns (65 yrs or older) during a one-year period are
      presented. The design was that of a case-control study involving 380 fallers
      seeking medical treatment and 342 unmatched controls selected randomly from the
      population register. The occurrence of a fall was shown by logistic regression
      analysis to be related to advanced age, presence of benzodiazepine in the serum,
      hypertrophy of the prostate, poor mental capacity, presence of chronic lung
      disease and asthma, use of analgesics and use of digitalis in the men, and to
      advanced age, poor mental capacity, presence of benzodiazepine in the serum, use
      of analgesics and non-occurrence of lower limb arthrosis in the women. The
      corresponding log-linear models showed advanced age and the presence of
      benzodiazepine in the serum to be independent risk factors for falling both in
      the men and women. Furthermore, the use of analgesics was related to falling in
      the women with normal mental capacities. No disease was independently associated
      with falls. The results suggest caution in the use of benzodiazepines among the
      elderly.

PMID- 8310280
TI  - Delayed discharge of elderly hospital patients--a study of bed-blockers in a
      health care district in Sweden.
AB  - With an ageing population an increased pressure on health care resources will be
      seen in most countries. Patients with delayed discharge from short-term
      hospitals, sometimes called "bed-blockers", are of special interest in Sweden,
      especially as liability for payments for these patients has been placed on the
      municipal authorities by a new reform in 1992. A retrospective study was made of
      428 bed-blockers above the age of 64 years from one health district in Uppsala
      during the two-year period 1987-1988. The median age was 81.6 years, and the
      majority were women. The patients had a median number of diagnoses of 4.1.
      Additional medical events/symptoms were noted in half of the patients after they
      had been classified as medically ready for discharge. Even though they were
      classified "medically ready" for discharge, they still needed care. One-third
      needed further rehabilitation and another 1/3 further medical attention. Only
      1/10 were independent in daily activities of living. At the final discharge 1/3
      actually returned home and 16% died on the acute ward. The results clearly
      demonstrate that these patients often still had further medical needs after the
      application for transfer. One crucial question, that needs discussion, is the
      vague definition of a "bed-blocker". Related questions are when and where should
      these patients be transferred, as well as the relevance of the term "bed-blocker"
      from ethical perspectives.

PMID- 8310281
TI  - Suggestion of concomitant changes of electric power consumption and childhood
      leukemia in Greece.
AB  - Over a 14-year period (1976-89) 679 deaths from childhood leukemia were
      registered in Greece and the corresponding mortality over this period declined by
      almost 70%, with no evidence of differential reduction by gender or population
      type. For each of the nine geographical regions of the country, slopes of
      decreasing mortality from childhood leukemia over the study period were
      calculated and correlated with the corresponding slopes of increasing electric
      power consumption over the 16-year period 1970-85 (allowing for a postulated
      latency of about 5 years). A positive association was noted, which however was
      not statistically significant (p approximately 0.26). Studies of similar nature
      conducted in larger countries over more extended periods could contribute to the
      resolution of the controversy surrounding the role of electric power-generated
      extremely low frequency electric and magnetic fields in the etiology of childhood
      leukemia.

PMID- 8310282
TI  - Science in the national interest.

PMID- 8310283
TI  - Psychiatry at UCSF.

PMID- 8310285
TI  - . . . as French ponder hosting AIDS summit.

PMID- 8310284
TI  - Psychiatry at UCSF.

PMID- 8310286
TI  - AIDS scandal embroils top French biologist...

PMID- 8310287
TI  - NIH drops bid for gene patents.

PMID- 8310288
TI  - Restating the risks of tamoxifen.

PMID- 8310289
TI  - Molecular biology with a strong Southern accent.

PMID- 8310290
TI  - The trials and tribulations of building a lab in the south.

PMID- 8310291
TI  - Laser-based analysis of carbon isotope ratios.
AB  - A laser technique for analysis of carbon-13:carbon-12 ratios with the specificity
      of laser resonance spectroscopy and the sensitivity and accuracy typical of
      isotope ratio mass spectrometers is reported. The technique is based on laser
      optogalvanic effect spectroscopy, in which an electrical (galvanic) signal is
      detected in response to the optical stimulation of a resonance transition in a
      gas discharge species. Carbon dioxide molecular gas lasers are used, with the
      probed transitions being identical to the lasing transitions. Measurements for
      carbon dioxide samples with 100-second averaging times yield isotopic ratios with
      a precision of better than 10 parts per million.

PMID- 8310292
TI  - Magnetic field effects on B12 ethanolamine ammonia lyase: evidence for a radical
      mechanism.
AB  - A change in radical pair recombination rates is one of the few mechanisms by
      which a magnetic field can interact with a biological system. The kinetic
      parameter Vmax/Km (where Km is the Michaelis constant) for the coenzyme B12
      dependent enzyme ethanolamine ammonia lyase was decreased 25 percent by a static
      magnetic field near 0.1 tesla (1000 gauss) with unlabeled ethanolamine and
      decreased 60 percent near 0.15 tesla with perdeuterated ethanolamine. This effect
      is likely caused by a magnetic field-induced change in intersystem crossing rates
      between the singlet and triplet spin states in the [cob(II)alamin:5'
      deoxyadenosyl radical] spin-correlated radical pair.

PMID- 8310293
TI  - Antigenic diversity and the transmission dynamics of Plasmodium falciparum.
AB  - The average age of humans at their first infection with Plasmodium falciparum is
      typically less than 1 year in most endemic areas. This has been interpreted as
      evidence of the high transmissibility of the parasite, with the implication that
      control of malaria will require high levels of coverage with a potential vaccine.
      This interpretation is challenged by mathematical models that demonstrate that
      the long period required to develop immunity to malaria permits a high risk (or
      low average age) of infection even when parasite transmissibility is low.
      Patterns of seroconversion to five antigenically distinct isolates of P.
      falciparum in a highly malarious area of Papua New Guinea indicate that each is
      only mildly transmissible and that malaria, as a construct of several such
      independently transmitted strains, has a basic reproductive rate (or
      transmissibility) that is an order of magnitude lower than other estimates.

PMID- 8310294
TI  - Diverse essential functions revealed by complementing yeast calmodulin mutants.
AB  - Calmodulin, a cytoplasmic calcium-binding protein, is indispensable for
      eukaryotic cell growth. Examination of 14 temperature-sensitive yeast mutants
      bearing one or more phenylalanine to alanine substitutions in the single
      essential calmodulin gene of yeast (CMD1) revealed diverse essential functions.
      Mutations could be classified into four intragenic complementation groups. Each
      group showed different characteristic functional defects in actin organization,
      calmodulin localization, nuclear division, or bud emergence. Phenylalanine
      residues implicated in calmodulin localization and nuclear division are located
      in the amino-terminal half of the protein, whereas those implicated in actin
      organization and bud emergence are located in the carboxyl-terminal half.

PMID- 8310295
TI  - Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin.
AB  - Obstruction of airways by viscous sputum causes lung damage in patients with
      cystic fibrosis (CF). Sputum samples from CF patients were shown to contain
      filamentous actin. Human plasma gelsolin, a protein that severs actin filaments,
      rapidly decreased the viscosity of CF sputum samples in vitro. Gc globulin and
      deoxyribonuclease I, proteins that sequester monomeric actin but do not sever
      actin filaments, were less efficient than gelsolin in diminishing sputum
      viscosity. These results suggest that gelsolin may have therapeutic potential as
      a mucolytic agent in CF patients.

PMID- 8310296
TI  - Kinetics of molecular chaperone action.
AB  - Molecular chaperones of the Hsp70 type transiently sequester unfolded segments of
      proteins and promote their correct folding. Target peptides were labeled with an
      environmentally sensitive fluorophore so that their binding to the molecular
      chaperone DnaK of Escherichia coli could be followed in real time. The two-step
      process was characterized by relaxation times of 27 seconds and 200 seconds with
      2 microM DnaK and 0.1 microM ligand at 25 degrees C. In the presence of adenosine
      triphosphate, the formation of the complex was greatly accelerated and appeared
      to be a single-exponential process with a relaxation time of 0.4 second. The
      binding-release cycle of DnaK thus occurs in the time range of polypeptide chain
      elongation and folding and is too fast to be stoichiometrically coupled to the
      adenosine triphosphatase activity of the chaperone (turnover number, 0.13 per
      minute at 30 degrees C).

PMID- 8310297
TI  - Paralysis and early death in cysteine string protein mutants of Drosophila.
AB  - Multimeric complexes of synaptic vesicle and terminal membrane proteins are
      important components of the neurotransmitter release mechanism. The csp gene of
      Drosophila encodes proteins homologous to synaptic vesicle proteins in Torpedo.
      Monoclonal antibodies demonstrate different distributions of isoforms at distinct
      subsets of terminals. Deletion of the csp gene in Drosophila causes a temperature
      sensitive block of synaptic transmission, followed by paralysis and premature
      death.

PMID- 8310298
TI  - Ca(2+)-induced Ca2+ release in response to flash photolysis.

PMID- 8310299
TI  - Fertilization and ion channels.

PMID- 8310300
TI  - Advanced and recurrent endometrial carcinoma: hormonal therapy.

PMID- 8310301
TI  - Chemotherapy of metastatic endometrial cancer.

PMID- 8310302
TI  - Cancers of the uterine cervix and endometrium: major issues and future research
      directions.

PMID- 8310303
TI  - Preinvasive cervical neoplasia.
AB  - The HPV has been identified as the causative agent for cervical neoplasia. The
      transforming mechanisms appear to be through inactivation of p105Rb or p53 by the
      oncoproteins E6 and E7 of HPV types 16 and 18. Because 2% to 24% of normal women
      test positive for these viral types and the incidence of neoplasia is less than
      1%, co-factors must play an important part in carcinogenesis. A search for these
      co-factors is underway.

PMID- 8310304
TI  - Early invasive disease: risk assessment and management.

PMID- 8310305
TI  - Prognostic factors in locally advanced carcinoma of the cervix treated with
      radiation therapy.

PMID- 8310306
TI  - Pathology of cervical carcinoma and its prognostic implications.

PMID- 8310307
TI  - Contemporary radiation treatment planning for patients with cancer of the uterine
      cervix.

PMID- 8310308
TI  - New approaches to radiation therapy in locally advanced carcinoma of the cervix.

PMID- 8310309
TI  - Locally advanced cervical carcinoma: the role of chemoradiation.

PMID- 8310310
TI  - Chemotherapy for cervix cancer.

PMID- 8310311
TI  - Pathology of hyperplasia and carcinoma of the endometrium.

PMID- 8310312
TI  - Endometrial cancer: prognostic factors.

PMID- 8310313
TI  - Limited disease: role of surgery.

PMID- 8310314
TI  - Limited endometrial carcinoma: adjuvant therapy.

PMID- 8310315
TI  - Radiation therapy and combined chemo-irradiation in advanced and recurrent
      endometrial carcinoma.
AB  - The advent of surgical staging for endometrial carcinoma has identified multiple
      combinations and degrees of various risk factors. Therefore, it is obvious that
      questions regarding adjuvant treatment in advanced disease must be generally
      stated and the answers, when available, may not be specifically applicable to
      individual patients. Hopefully ongoing and future prospective trials will help to
      resolve questions about the proper role of RT and/or chemo-irradiation and the
      proper technique and treatment volume when RT is used.

PMID- 8310316
TI  - A group model for gay and lesbian clients with chronic mental illness.
AB  - This article examines the creation of a gay affirmative group model that focuses
      on the unique social, developmental, and psychoeducational needs of lesbian and
      gay clients who attend psychiatric day treatment. The author discusses how these
      clients' psychosocial potential can be maximized in a group that addresses issues
      related to their sexual orientation, including their double stigmatization as
      both mental patients and homosexuals. The following modifications of traditional
      group interventions are illustrated: (1) the tolerance of primitive interpersonal
      styles; (2) the encouragement of differentiation; and (3) the need for a
      structured, nonconfrontational approach. These principles, which lead to enhanced
      group safety and cohesion, are contrasted with those of a more traditional
      "coming-out" group. Overcoming resistance and homophobia among staff and other
      clients is outlined, as is establishing the group as an integral component of a
      gay-sensitive treatment structure in a mental health agency.

PMID- 8310317
TI  - An assessment of practitioner cross-racial treatment experiences.
AB  - This study sought to determine differences in the cross-racial practice
      experiences of white and minority social services practitioners. Fifty-three
      counselors in a Veterans Administration outreach center evaluated various aspects
      of their cross-racial practice experiences. Both white and minority counselors
      perceived themselves to work equally well with white clients, but white
      counselors perceived themselves to be less effective when working with minority
      clients. The majority of white and minority counselors reported identifying the
      source of white clients' problems as being internal and that of minority clients'
      problems as being external. This finding was interpreted as being a possible bias
      against white clients on the part of both white and minority practitioners. White
      counselors reported experiencing less client credibility, and minority counselors
      reported more incidents of racism. Implications for social work are discussed.

PMID- 8310318
TI  - Licensure of sheltered-care facilities: does it assure quality?
AB  - In California, licensure was intended to assure a minimum level of quality in
      sheltered-care facilities for the mentally ill population. This longitudinal
      study relates characteristics of facilities, their residents, and communities to
      subsequent licensure and considers differences between licensed and unlicensed
      facilities at follow-up. Initial interviews were completed in 214 facilities in
      1973 six months before the implementation of the California Residential
      Facilities Licensing Act. Follow-up interviews occurred in 1985. Results indicate
      that although licensure occurred with greater frequency among facilities serving
      the most disabled population, licensure neither predicts nor has as its apparent
      consequence the development of higher-quality facilities. An alternative approach
      to quality assurance is offered.

PMID- 8310319
TI  - Starting a support group for families and partners of people with HIV/AIDS in a
      rural setting.

PMID- 8310320
TI  - Neglected victims of murder: children's witness to parental homicide.
AB  - Children who witness parental homicides are emotionally traumatized, stigmatized,
      and deeply scarred by a terrifying event. They often exhibit debilitating
      symptoms comparable to those of posttraumatic stress disorder. As attention is
      focused on the deceased and on the perpetrator of the crime, the child witnesses
      inadvertently become the neglected victims. A case report of two such children
      who observed their mother being murdered by their father is presented. Theories
      of psychosocial development and social learning guided the assessment and
      intervention phases. Behavioral and expressive therapeutic treatment strategies
      that helped the children work through the resultant anxiety and underlying grief
      are delineated, and family intervention practices that served to improve
      interaction and communication patterns are described. Further discussion focuses
      on the potential intergenerational cycle of violence and on a sociocultural
      perspective of family violence within an ecological framework.

PMID- 8310321
TI  - The paradox of the advantaged elder and the feminization of poverty.
AB  - The construction of social definitions is important, as these definitions are
      ultimately translated into public policies. This article explores the emergence
      of the concepts of the advantaged elder and the feminization of poverty. It is a
      paradox that society has simultaneously embraced these two concepts when the
      elderly population, especially the subpopulation of those who are very old, is
      overwhelmingly women. The theoretical shortcomings of both concepts are examined,
      and a broader model of economic well-being that emphasizes the interactive nature
      of gender, race, and class is proposed. The implications of societal perceptions
      of the advantaged elder and the feminization of poverty for older women are
      addressed.

PMID- 8310322
TI  - Life themes of native Hawaiian female elders: resources for cultural
      preservation.
AB  - Women of color represent a growing segment of the rapidly increasing aging
      population in the United States, and yet descriptive and epidemiological data on
      this population remain sparse. This article examines the life experiences of
      aging native Hawaiian women. Oral history methodology is used to collect
      information on the life experiences of six female elders (kupuna) to identify
      life themes and cultural values and, more important, to contribute to cultural
      preservation. Implications for social work policy and research are identified.

PMID- 8310323
TI  - Child custody decisions in families experiencing woman abuse.
AB  - Both battered women and their partners are at risk for abusing their children,
      but social work practitioners are often unaware of the much greater risk
      presented by men who batter. This article reviews the scientific literature
      comparing the risk that battered women and men who batter will physically abuse
      their children. Several tenets of social work practice lore are challenged, and
      practitioners are cautioned about the use of psychological tests and profiles to
      judge child abuse potential and parenting ability. The hazards of mediation and
      joint custody are discussed, as well as the limitations of treatment for men who
      batter.

PMID- 8310324
TI  - The party isn't over: the agency role in the retention of public child welfare
      caseworkers.
AB  - Nationwide, social services agencies continue to report difficulties in the
      retention of public child welfare caseworkers. As service demands placed on the
      child welfare system continue to increase, the need for an experienced and
      competent work force becomes imperative. Previous studies have identified the
      reasons for the high turnover rate among child welfare caseworkers. This article
      reports the findings of an exploratory study to identify factors that may
      influence some caseworkers to continue employment in public child welfare when so
      many others are leaving. From comprehensive focused interviews with 23
      caseworkers, the following four factors of retention emerged: (1) mission, (2)
      goodness of fit, (3) supervision, and (4) investment. The importance of the
      relationship with the agency and the four factors in the retention of public
      child welfare caseworkers is discussed.

PMID- 8310325
TI  - Mothers in prison: meeting the prerequisite conditions for permanency planning.
AB  - This article describes a study of incarcerated mothers in New York State prisons
      who had children in foster care. Prerequisite conditions for permanency planning
      activities between mothers and caseworkers are examined, with a focus on the
      incidence of correspondence, telephone contact, and notification of court
      hearings. Although most of the mothers questioned reported having telephone
      contact or correspondence with caseworkers, a sizable number reported having
      neither, and less than half were familiar with the procedures that would enable
      them to appear for court hearings. Failure to engage in such activities
      jeopardizes the parental status of the incarcerated mother. Recommendations are
      made for changes in policies and practice that facilitate increased
      correspondence and telephone contact as well as notification of and attendance at
      court hearings.

PMID- 8310326
TI  - Homelessness in rural areas: causes, patterns, and trends.
AB  - Although homelessness in urban areas has been examined extensively, little
      attention has been given to the problem of homelessness in rural areas. This
      article reports the findings from a 1990 statewide study of rural homelessness
      funded by the National Institute of Mental Health. During the six-month data
      collection period, 919 homeless adults were interviewed; 247 were heading family
      units, and 480 children were in these families. More than two-thirds of these
      families were headed by single parents. Implications of the findings for
      providing short-term emergency assistance and longer-term policy-making are
      presented.

PMID- 8310327
TI  - [Destructive and cystic-bullous lung changes in high resolution CT].

PMID- 8310328
TI  - [Hypertrophic osteoarthropathy (Pierre-Marie-Bamberger syndrome) as a
      paraneoplastic phenomenon].

PMID- 8310329
TI  - [The evolution of interventional radiology up to the year 2000].

PMID- 8310330
TI  - [William David Coolidge (1873-1975). A report on the scientific achievements of
      one of the pioneers of radiology].

PMID- 8310331
TI  - [Diffuse axonal injuries and other closed injuries of the brain. Suggestions for
      a classification scheme].
AB  - The author presents a brief account of recent findings pertaining to different
      types of closed brain injuries. He supplements classical types of injuries by the
      concept of diffuse axonal injuries and brain swelling. The classification is
      based on diagnosis by the CT picture and clinical symptoms. The suggested schema
      of classification of different injuries alters Petit's classification of closed
      brain injuries.

PMID- 8310332
TI  - [Results of regeneration after peripheral nerve injuries].
AB  - Based on a group of distal injuries of the median and ulnar nerve the authors
      evaluate the results of peripheral nerve regeneration. For evaluation of the
      results and comparison with other work they emphasize the necessity of adherence
      to objective criteria of a useful degree of reinnervation. In their opinion the
      most suitable criterium is evaluation of sensitive reinnervation respecting the
      discrimination test up to 12 mm in the entire autozone of the nerve. The results
      of suture depend on the technique, interval (injury-operation) and the patient's
      age. In acute operations 45% of the patients of all age groups achieved the
      useful grade of sensitive regeneration. In late operations, where the degree of
      useful regeneration was achieved only in 19% of patients, the authors draw
      attention to the fact that a successful outcome was achieved only in patients
      under 30 years. The main prerequisite of successful regeneration of peripheral
      nerves in according to the authors early diagnosis and treatment in the acute
      period. With regard to the declining regeneration potential with advancing age
      early treatment is much more important in patients older than 30 years.
      Microsurgical technique is a condition sine qua non.

PMID- 8310333
TI  - [Surgical endoscopy--analysis of 6 years' activity].
AB  - Fibroscopy of the digestive system which in the majority of developed countries
      is quite common is in our country still not available in an adequate extent. The
      authors evaluate their experience in a surgical department covering a six-year
      period. A total of 4436 fibroscopic examinations were made incl. 3821
      gastroscopies 615 ERCP and examinations of the papilla Vateri. They describe
      their experience with urgent endoscopy on account of haemorrhage into the GIT,
      pancreatitis or cholangitis. They emphasize the advantages of a maximal extension
      of endoscopic methods and their advantages, as compared with classical
      examination methods.

PMID- 8310334
TI  - [Laparoscopic cholecystectomy without cholangiography].
AB  - The results assembled in a group of 260 patients subjected to laparoscopic
      cholecystectomy without i.v. cholangiography (0.38% residual stones, entirely
      successful perioperative endoscopic treatment, no biliary lesion) confirm that a
      low incidence of residual cholelithiasis, elimination of revision on account of
      concrements in the bile duct and absence of biliary lesions can be achieved
      without obligatory preoperative cholangiography even in a non-selected clinical
      group. When therapeutic "splitting" is used, peroperative selective
      cholangiography is not necessary.

PMID- 8310335
TI  - [Emergency endoscopic papillotomy].
AB  - The authors describe their experience with urgent endoscopic procedures of the
      papilla Vater. They consider septic cholangitis and acute pancreatitis
      indications for endoscopic papillotomy. The authors made a total of 27
      operations, incl. 22 on account of pancreatitis and five on account of
      cholangitis. One female patient with necrotizing pancreatitis caused by a
      protracted sepsis and multiorgan failure, died. Otherwise there were no serious
      complications; after the majority of operations a steep drop of pathological
      laboratory values was recorded. One of the most important factors for successful
      endoscopic intervention is in the authors' opinion rapid action. With regard to
      the favourable initial results the authors recommend a detailed multi-centre
      prospective randomized study.

PMID- 8310336
TI  - [Laparoscopic cholecystectomy].
AB  - The authors present an account of their experience assembled during one year with
      laparoscopic operations of the gallbladder. They indicated 248 patients for CHE
      incl. 237, i.e. 95.6%, for laparoscopic CHE. No deaths, no major complications,
      6.5% conversions in elective indications, 23% in acute indications. Six patients
      with residual choledocholithiasis are in the authors' opinion a signal calling
      for more accurate detection of CHLDL before and during LCHE.

PMID- 8310337
TI  - [New instruments for laparoscopy].
AB  - The author describes new laparoscopic instruments for blunt dissection of tissue,
      that also make an abdominal wall suture more simple. The instruments are very
      simple from the technical point of view. They can be manufactured even under very
      basic conditions. By using these instruments it is possible to spare more
      advanced and expensive standard laparoscopic instruments as well. They make it
      possible for the accurate and sensitive tissue dissection. Forestalling thus an
      injury to biliary duct, the worse complication in laparoscopic operations, to
      occur. The instrument has been regularly used in clinical practice and proved
      good.

PMID- 8310338
TI  - [Choledochal cysts in children].
AB  - The author presents an account of cysts of the choledochus in children. With
      present possibilities of ultrasonic examination in abdominal pain, jaundice or a
      palpable resistance in the abdomen cystic formations in the subhepatic region are
      diagnosed with increasing frequency in child age and are operated. At present the
      best and most permanent results are achieved after extirpation of the cyst and
      substitution of the extrahepatic biliary pathways by a jejunal loop, as
      recommended by Roux.

PMID- 8310339
TI  - [Antimicrobial prophylaxis with cefamandole in biliary tract surgery].
AB  - The authors present their experience with antimicrobial prophylaxis using
      cephalosporin of the second generation--cefamandole--in biliary surgery.
      Cefamandole was administered to 28 patients operated for a biliary affection and
      hospitalized at the Surgical Clinic of the Third Medical Faculty in Prague.
      Cefamandole was administered after 8-hour intervals in 1 g doses up to 48 hours
      after the first dose. For antimicrobial prophylaxis patients were selected,
      included after previous investigations in the high risk group. In the patients in
      addition to microbiological examination of bile the cefamandole levels in bile
      and serum were compared. The presented results proved that cefamandole
      administration is justified in the prevention of infectious complications after
      operations of the gallbladder and biliary pathways because of its antibacterial
      and pharmacokinetic properties.

PMID- 8310340
TI  - [Appendicitis, pseudoappendicitis and Crohn's disease].
AB  - Abdominal pain which is a basic symptom of Crohn's disease was in a group of 53
      patients treated in 1981-1982 at the Surgical Clinic of the Third Medical Faculty
      in Prague 10 the initial symptom in 73.3% of the patients. The inflammation was
      most frequently in the terminal ileum and in the ileocaecal region, in the
      authors' group in 49.0% and 30.2% resp. In 18 patients appendectomy was
      performed, incl. 10 where it was performed a long time before the development of
      the first complaints caused by Crohn's disease. In these patients the authors do
      not assume, because of the long symptom-free period, that there existed a direct
      relationship with Crohn's disease which developed later. In six patients during
      laparotomy performed on account of pain in the right hypogastrium acute terminal
      ileitis, the first stage of Crohn's disease, was detected. In two patients the
      initial finding was granulomatous appendicitis.

PMID- 8310341
TI  - [Uncommon causes of hemorrhage in the upper digestive tract].
AB  - The authors submit data on 12 patients with infrequent and rare sources of
      haemorrhage from the upper digestive tract, emphasize diagnostic difficulties,
      frequent relapses of haemorrhage and frequent operations associated with it. They
      draw attention to the high mortality which is three times higher than in "common"
      sources of haemorrhage and the large consumption of blood and blood derivatives.
      They do not doubt the fundamental role of endoscopy in the diagnostic process and
      finally provide evidence of the difficult leading position of the surgeon in the
      treatment of these patients.

PMID- 8310342
TI  - [Musculocutaneous flaps in the treatment of chronic decubitus ulcers in the
      ischial region].
AB  - In a group of 28 decubiti in 21 paraplegic patients, operated during the past
      five years the authors draw attention to the advantages of the use of three types
      of musculocutaneous (MC) flaps for surgical and radical treatment of ischial
      decubiti. The method using musculocutaneous flaps makes it possible to restore a
      relatively satisfactory cover of the defect by a multilayer long-lasting flap.

PMID- 8310343
TI  - [Fasciocutaneous flaps].
AB  - Fasciocutaneous flaps proved useful for covering soft tissue defects in the
      region of the leg. After experience with the use of these flaps in six patients
      the authors recommend this method for covering these defects. In all patients
      very satisfactory results were achieved.

PMID- 8310344
TI  - [Transplantation of a horseshoe kidney].
AB  - Report of a case, in which a horseshoe kidney was divided and transplanted to two
      recipients, is described. Both transplantations were successful. This anomaly is
      not a contraindication to its use for transplantation.

PMID- 8310345
TI  - [History of surgery in the Czech Republic].
AB  - There are not only great personalities and a great credit they take for surgery
      in our country, but also the life, organisations and work of barber surgeons in
      the time before Joseph II. We demonstrate their "art" from the treatment of
      wounds, fractures, luxations, hernias atc. to venesections and amputations. Also
      shown is how much they could charge for each type of treatment or operations as
      specified in a 1972 official notice.

PMID- 8310346
TI  - [100th anniversary of the birth of Prof. Jan Knazovicky--the first president of
      the Medical School in Kosice and founder of the surgical school in Kosice].

PMID- 8310347
TI  - Breast cancer avoidance--is there really a strategy of hope?

PMID- 8310348
TI  - Death from pneumonia in young children--time for action.

PMID- 8310349
TI  - Perspectives on AIDS control in Zambia.

PMID- 8310350
TI  - The socio-economic determinants of the AIDS epidemic in South Africa--a cycle of
      poverty.

PMID- 8310352
TI  - Alternative medicine--a rational viewpoint is necessary.

PMID- 8310351
TI  - Paediatric HIV/AIDS in schools.

PMID- 8310353
TI  - Smoking guns and public health.

PMID- 8310354
TI  - The prevalence of diabetes mellitus and impaired glucose tolerance in a group of
      urban South African blacks.
AB  - The prevalence of diabetes mellitus and impaired glucose tolerance (IGT) was
      determined in 479 urbanised South African blacks (141 men and 338 women) of Zulu
      descent selected by cluster sampling in a suburb of Durban. All subjects
      underwent a modified glucose tolerance test whereby fasting and 2-hour post
      glucose (75 g) plasma glucose levels were measured. On the basis of the revised
      World Health Organisation criteria, the overall prevalence of diabetes was 4.2%
      and of IGT 6.9%; the age- and sex-adjusted prevalences were 5.3% and 7.7%
      respectively. Diabetes mellitus was more common in women (5.2% v. 2.3%), while
      the reverse was true of IGT (5.5% v. 11.5%). The mean age-adjusted body mass
      indices (BMIs) of diabetic (31.3 +/- 1.9) and IGT (29.7 +/- 1.9) subjects were
      significantly higher than those of the group with normal glucose tolerance (28 +/
      0.5). Female subjects with all types of glucose tolerance had significantly
      higher mean BMIs than men. There was a significant correlation between BMI and
      both fasting glucose (r = 0.16; P = 0.0039) and 2-hour plasma levels (r = 0.15; P
      = 0.0065) in the women, while in men only the fasting levels showed such a
      relationship (r = 0.21; P = 0.01719).

PMID- 8310355
TI  - Avascular necrosis of bone following renal transplantation.
AB  - This study was undertaken to determine the incidence and clinical features of
      avascular necrosis of bone in 69 transplant recipients all of whom had a
      functioning allograft for at least 12 months. An attempt was also made to
      identify any potential predisposing factors. The patients were assessed by an
      orthopaedic surgeon. The diagnosis of avascular necrosis was made on the basis of
      radiographs and isotope bone scans. Fourteen patients (20.2%) developed avascular
      necrosis with a mean onset of 19 months post-transplantation. The hip joint was
      most commonly affected. The isotope bone scan was the most sensitive diagnostic
      tool; abnormalities were detected before the onset of symptoms in 4 patients.
      Avascular necrosis was more common in Indian transplant recipients and was also
      associated with: (i) cadaver transplants; (ii) more frequent bouts of acute
      rejection (P < 0.05); and (iii) a greater incidence of other steroid-associated
      side-effects (P < 0.05). Alcohol consumption and radiological evidence of
      osteoporosis were more prevalent in the avascular necrosis group (42.8% v. 29.0%
      and 28.5% v. 7.2% respectively). Avascular necrosis did not correlate with age,
      sex, renal function at 1 year or severe secondary hyperparathyroidism. This study
      suggests that corticosteroid therapy plays an important role in the pathogenesis
      of avascular necrosis. Excessive alcohol consumption and osteoporosis also appear
      to be risk factors.

PMID- 8310356
TI  - Hepatitis B virus prevalence in two institutions for the mentally handicapped.
AB  - A comparative study of the prevalence of hepatitis B virus infection in two
      institutions for the mentally handicapped was carried out between April and
      November 1989 and April and August 1991. The institutions were situated within 10
      km of each other in north-eastern Johannesburg. One institution had a
      significantly higher prevalence of virus markers, 68% (139 of 203) compared with
      23% (40 of 176), was in poorer condition and had more severely handicapped
      residents with more aggressive behaviour. However, the most important difference
      between the two institutions was that residents at the higher-prevalence
      institution were admitted at a considerably younger age. Younger individuals
      appear to be more susceptible to infection and are more likely to develop
      persistent infection, thus contributing to a greater pool of infection in the
      institution.

PMID- 8310357
TI  - The prevalence of psychiatric disorders at a primary care clinic in Soweto,
      Johannesburg.
AB  - A pilot study to assess the prevalence of psychiatric disorders in a primary care
      clinic in Soweto was carried out at the Zola Community Health Centre in May 1991.
      Interviews were carried out by trained primary care clinic staff. The findings
      were reviewed and analysed by the authors. The prevalence of psychiatric
      disorders was found to be 14.38%. Methodological problems are listed and the
      results are discussed.

PMID- 8310358
TI  - Intravenous nitroglycerin as a tocolytic agent for intrapartum external cephalic
      version.

PMID- 8310359
TI  - The prevalence of maternal medication ingestion in the antenatal period.
AB  - The prevalence of ingestion of medication by pregnant women was recorded in 236
      patients attending the antenatal clinics at New Somerset and Peninsula Maternity
      Hospitals. Patients were interviewed over two periods, 23-26 July and 2-12
      December 1991. Of these women, 168 (71.2%) took a total of 283 drugs from 18
      different categories. One hundred and forty women (59%) took prescribed and 68
      (28.8%) non-prescribed medications. The most commonly used medicines were
      analgesics, cough and cold medicines, antibiotics, laxatives and antacids.
      Analgesics that contain aspirin constituted 13.8% of self-administered medicines
      and 2% of prescribed medicines. The most common sources of non-prescribed
      medication were pharmacies (60%), followed by supermarkets (32.5%). One hundred
      and sixty-two women (68.6%) received no advice on medication during their
      pregnancy. Of those who received advice, formal sources
      (doctor/nurse/pharmacist/midwife) accounted for 56.8% and informal sources
      (family/friends/magazines) for 43.3% of advice; 59.7% of women did not know that
      certain medicines are unsafe during pregnancy. Our data indicate that pregnant
      women in Cape Town take a large number of medicines, often without being aware of
      the potential adverse effects. This study shows the need for education in this
      regard, especially at antenatal clinics, pharmacies and supermarkets.

PMID- 8310360
TI  - Are anticardiolipin antibodies responsible for some of the complications of
      severe acute Plasmodium falciparum malaria?
AB  - What were first called simply false-positive Wassermann reactions and then lupus
      anticoagulant are now known as antiphospholipid or anticardiolipin antibodies
      (ACA). These are known to cause a tendency to thrombosis and are frequently
      present in many neurological conditions and infections. The pathological
      significance of these antibodies in acute infections, if any, is unknown. We
      investigated the presence of these antibodies in Plasmodium falciparum malaria in
      an endemic area in Natal/KwaZulu, and attempted to correlate the presence of this
      antibody with cerebral manifestations. Immunoglobulin G-anticardiolipin
      antibodies measured by enzyme-linked immunosorbent assay occurred significantly
      more frequently in 62 patients with acute Plasmodium falciparum malaria (33.9%)
      than in 37 control subjects (2.7%) (P < 0.0001). There was no significant
      difference in the mean parasite loads in those patients who were positive for ACA
      (1.75%) and those who were negative (1.59%) (P = 0.83). No correlation was found
      between parasite load and ACA levels in the patient group, or between the number
      of cerebral manifestations in patients with and without the antibody. The
      frequency of splenomegaly was not significantly different in patients with and
      without ACA (P = 0.06). We conclude that there is a high prevalence of ACA in
      acute falciparum malaria. The pathological significance of this antibody and its
      relationship to complications, especially cerebral ones, warrant greater
      attention and may improve the understanding of cerebral malaria and its
      management.

PMID- 8310361
TI  - Sneddon's syndrome with anticardiolipin antibodies--complications and treatment.
AB  - We investigated 2 patients with Sneddon's syndrome, elevated anticardiolipin
      antibodies and systemic complications, which included stroke, habitual abortions,
      cardiac valvular lesions, acrocyanosis, hypertension and renal insufficiency.
      Treatment with a combination of immunosuppressive agents and warfarin or aspirin
      prevented further complications and improved renal function. It is important for
      those in different specialties to be aware of this potentially treatable
      disorder.

PMID- 8310362
TI  - AIDS prevention in South Africa. A perspective from other African countries.

PMID- 8310363
TI  - AIDS education in schools--awareness, attitudes and opinions among educators,
      theology students and health professionals.
AB  - A project was undertaken in Grahamstown to assess the level of AIDS awareness,
      attitudes towards AIDS and opinions as to how and whether education programmes
      for schoolchildren should be planned. Opinions were canvassed initially by means
      of a questionnaire to three groups of professionals who could become involved in
      AIDS education programmes: student teachers and lecturers in the Department of
      Education at Rhodes University, theology students at the local Theological
      College and health care professionals at Settlers' Hospital. Each group was then
      asked to attend a lecture about AIDS at which slides were shown of actual cases
      of the disease and its complications. A slightly modified version of the original
      questionnaire was then administered after 6 weeks to assess any changes in
      awareness, attitudes and opinions. The study did not attempt to establish the
      permanence of any such changes.

PMID- 8310364
TI  - The National Health Services Commission, 1942-1944--its origins and outcome.
AB  - An analysis of the origins and outcome of the Gluckman Commission is relevant to
      the current health service debate in South Africa. Fundamental to the report's
      recommendations was the establishment of a unitary health service responsible for
      all health care functions within the Union of South Africa. On this proposal
      rested the success of the other key recommendations. The sequence of events
      following the publication of the report demonstrated that piecemeal
      restructuring, determined primarily by political considerations, failed. Unless
      policy-makers today are committed to a unitary health system with democratic
      control, current initiatives to restructure health services will probably remain
      parochial, contributing little to the improvement of health care for all South
      Africans.

PMID- 8310365
TI  - Emergency medicine in South Africa.

PMID- 8310366
TI  - Under-reporting of AIDS.

PMID- 8310367
TI  - AIDS and the social irresponsibility of the insurance industry.

PMID- 8310368
TI  - Traditional healers and AIDS prevention.

PMID- 8310369
TI  - Age of occurrence of breast cancer in black women.

PMID- 8310370
TI  - Warning--misleading malaria advice.

PMID- 8310371
TI  - Malaria prophylaxis and treatment.

PMID- 8310372
TI  - Malaria among exiles returning to South Africa.

PMID- 8310373
TI  - Practising of medicine by pharmacists.

PMID- 8310374
TI  - The man with the golden pen.

PMID- 8310375
TI  - Antiphospholipid syndrome--an unusual presentation.

PMID- 8310376
TI  - Foreign bodies in the ear canal--take them out, but look behind!

PMID- 8310377
TI  - The rapid laboratory diagnosis of tuberculosis.

PMID- 8310379
TI  - Foreign doctors.

PMID- 8310378
TI  - Westernisation and human development.

PMID- 8310380
TI  - Expanded focus for a changing world.

PMID- 8310381
TI  - Proper usage of brain retractors in the interhemispheric fissure based on MRI
      microanatomy: technical note.
AB  - The authors present a method of the surgical dissection of the interhemispheric
      fissure based on high resolution magnetic resonance images (MRI). The dissection
      of the interhemispheric space is not easy because the brain surfaces are tightly
      adherent in the interhemispheric fissure. In other words, in the interhemispheric
      fissure, the apices of the gyri are touching and are tightly bound together. This
      microanatomy is clearly revealed using high resolution three-dimensional MRI. The
      principle of the usage of the brain retractor is to apply them symmetrically in
      order to give an even tension to both sides. However, in the interhemispheric
      dissection, this principle should be slightly modified. Namely the brain
      retractors should be placed on the crest of gyri on both sides to avoid the
      injury of small arteries located in the sulci by the edge of the brain
      retractors.

PMID- 8310383
TI  - Facial nerve outcome after acoustic neuroma surgery.
AB  - Factors influencing facial nerve preservation and function in acoustic neuroma
      surgery were studied in 108 cases. Anatomic preservation of the nerve was
      inversely related to tumor size and improved as the series progressed. When the
      nerve was saved, normal postoperative function was inversely related to tumor
      size and was more common if the cochlear nerve was also saved. Most intact nerves
      eventually recovered some function, but late function was seldom completely
      normal unless there was some early recovery. The results demonstrate the
      importance of tumor size, operator experience, and ease of dissection on facial
      nerve outcome.

PMID- 8310382
TI  - Selective intra-arterial chemotherapy with a combination of etoposide and
      cisplatin for malignant gliomas: preliminary report.
AB  - We administered selective intra-arterial chemotherapy consisting of a combination
      of etoposide and cisplatin to 20 patients with malignant glioma (seven with
      recurrent and six with enlarged tumors after initial treatment, and seven newly
      diagnosed patients). Evaluation of efficacy was based on computed tomographic and
      magnetic resonance imaging findings. In the process of establishing a safe
      technique for superselective intra-arterial chemotherapy, we encountered
      cerebrovascular accidents in two patients (after etoposide in one and after
      etoposide plus cisplatin in the other). In these two cases, 100 mg/m2 of
      etoposide and 100 mg/m2 of cisplatin were delivered via the horizontal segment of
      the middle cerebral artery (M1) or the tip of the basilar artery, with the
      infusion time reduced to 20 minutes. Thereafter, the etoposide was diluted, and
      the doses of both drugs were reduced to 80 or 50 mg/m2, and finally to 60 mg/m2,
      and both were infused over 60 minutes. In addition, for prevention of local
      spasm, papaverine hydrochloride and nicardipine were given via the same catheter
      at 5-minute intervals during administration of etoposide and cisplatin. No
      complications developed in the later cases. Thereafter, selective intra-arterial
      infusion of etoposide and cisplatin into the anterior cerebral artery, middle
      cerebral artery, posterior cerebral artery, or the basilar artery for malignant
      gliomas in the basal ganglia, internal capsule, and brainstem--a procedure
      generally considered risky in terms of potential complications--was performed
      safely, with tolerable side effects. Computed tomography and magnetic resonance
      imaging indicated improvement in 13 patients, including four whose tumors
      completely disappeared. This method of intra-arterial chemotherapy may be useful
      as an adjuvant treatment for malignant glioma.

PMID- 8310384
TI  - Rapid bony destruction with pyogenic vertebral osteomyelitis.
AB  - We report the case of a previously healthy woman who had an extremely rapid
      progression of pyogenic vertebral osteomyelitis. The plain film radiographs from
      1 month before admission, from the time of admission, and from her 1 year follow
      up are presented. Although it is a well known fact that pyogenic vertebral
      osteomyelitis can evolve rapidly and that the radiographic images often lag
      behind the clinical symptoms, it is rare to find a case with such clear
      radiographic documentation. A film that was interpreted as having mild arthritic
      changes, 1 month before admission, progressed to one that demonstrates severe
      bony destruction with a kyphotic angulation of 90 degrees. The current methods of
      diagnosis and treatment of pyogenic vertebral osteomyelitis are reviewed.

PMID- 8310385
TI  - Endovascular platinum coil embolization of incompletely surgically clipped
      cerebral aneurysms.
AB  - The natural history of incompletely clipped intracranial aneurysms is largely
      unknown. The authors present two cases of residual aneurysm filling after
      surgical clipping which were successfully managed by intravascular placement of
      platinum coils. Management of residual aneurysms and possible future role of
      transcatheter therapy are discussed.

PMID- 8310387
TI  - Magnetic resonance imaging of C2 segmental type of vertebral artery.
AB  - Two cases with C2 segmental type of vertebral artery (VA) were reported. One case
      was a 64-year-old man, who was referred to our hospital suffering from vertigo,
      ataxia, and right facial palsy. Computed tomography (CT) scan showed multiple
      lacunae in the basal ganglia bilaterally. Another case was a 47-year-old man,
      complaining of left hemiparesthesia. A small high density area with a little
      enhancement was seen in the right parietal region in CT scan, and the lesion was
      diagnosed as cavernous angioma. Angiography of both cases depicted the vertebral
      artery not passing through the transverse foramen of the Atlas, but running
      medioposterior to it, and magnetic resonance imaging (MRI) and CT findings showed
      the vertebral artery running between the Atlas and Axis, and entering into the
      spinal canal. In our experience of 1669 sides in 1436 cases, such anomaly of the
      vertebral artery was found in ten cases including the two abovementioned. Six
      cases of such anomaly have previously been reported, but demonstration of the VA
      coursing between Atlas and Axis by MRI has not been published in the literature.
      During surgical therapy on the upper cervical spine, especially when using a
      posterior approach, or C1-C2 lateral puncture, the possibility of an anomalous
      vertebral artery, as in our cases, should be taken into consideration.

PMID- 8310386
TI  - Cardiac malignant fibrous histiocytoma metastasizing to the brain: development of
      multiple neoplastic cerebral aneurysms.
AB  - We report a case in which bilateral occipital brain metastases and neoplastic
      cerebral aneurysms developed from primary cardiac malignant fibrous histiocytoma.
      The origin of metastases was confirmed at autopsy. The clinical presentation,
      radiographic features, and autopsy findings are presented along with a
      histopathologic analysis of the tumor.

PMID- 8310388
TI  - Triple primary brain tumors of different histological types: case report.
AB  - We report a case of triple primary intracranial tumors of different histologic
      types: meningioma, astrocytoma, and pituitary adenoma. Von Recklinghausen's
      disease or other etiologic factors supposedly associated with multiple primary
      brain tumors were not recognized in this 64-year-old female patient. Triple
      primary brain tumors with no association of von Recklinghausen's disease are rare
      -there is only one reported case with histologic studies.

PMID- 8310389
TI  - Anterior fossa dural arteriovenous malformation supplied by bilateral ethmoidal
      arteries.
AB  - Two cases of dural arteriovenous malformation (AVM) involving the base of the
      anterior cranial fossa are reported. The nidi in both cases were located in the
      region of the left cribriform plate and mainly supplied by the anterior ethmoidal
      arteries of both sides, draining through pial veins into either the cavernous
      sinus or the superior sagittal sinus. In the first case neurologic symptoms
      resulted from transient frontal lobe dysfunction presumably due to abnormal
      venous drainage, and the second case presented with subarachnoid hemorrhage
      caused by rupture of dural AVM at the base of the anterior fossa. Both cases were
      surgically managed and the AVMs were successfully obliterated. This unique
      subgroup of dural AVM in the anterior fossa is thoroughly reviewed in the
      literature, and the epidemiology, symptomatology, neuroradiology, surgical
      treatment, and associated vascular lesions are discussed.

PMID- 8310390
TI  - Bilateral decompressive craniectomy for worsening coma in acute subarachnoid
      hemorrhage. Observations in support of the procedure.
AB  - Bilateral craniectomy in a woman comatose and decerebrate after a subarachnoid
      hemorrhage, resulted in normal mentation in 3 days. The dramatic recovery is
      unmatched in our experience. The rationale rested on clinicopathologic studies
      showing that in such cases brain swelling was the cause of death, the brain being
      otherwise intact. Emergency surgery to relieve the tamponade seemed reasonable.
      The question is whether the procedure has a role in those patients who fail to
      respond to current therapeutic measures. The arguments in favor, presented
      herein, are illustrated by three pathologic studies selected from our longtime
      experience.

PMID- 8310391
TI  - Primitive trigeminal artery associated with cavernous aneurysm: case report.
AB  - A case of unruptured aneurysm at the junction of the cavernous segment of the
      right internal carotid artery and the primitive trigeminal artery (PTA) is
      presented. The posterior circulation was not dependent on PTA, thus the PTA was
      of an adult type in this case. This patient was successfully treated by external
      carotid artery-anterior temporal artery long vein graft bypass, internal carotid
      artery ligation at neck, and PTA clipping through the right subtemporal approach.
      A follow-up angiography showed thrombotic occlusion of the aneurysm. In review of
      the literature, there are 27 cases reported of PTA aneurysm; among them only 11
      cases, including ours, treated surgically. The surgical treatment plan for PTA
      aneurysm, according to the review of literature is discussed.

PMID- 8310392
TI  - Growing skull fracture of the orbital roof.
AB  - One year after trauma, diplopia, limitation of ocular movements on the left side,
      orbital asymmetry, and a growing skull fracture on the orbital roof were reported
      in an extraordinary case. While presenting this extraordinary localization of
      growing skull fractures, the anatomy, pathogenesis and the natural evolution of
      these lesions still remain obscure.

PMID- 8310393
TI  - Penetration of the intracranial cavity by an object driven through the orbit.

PMID- 8310394
TI  - Factors affecting functional prognosis in survivors of primary central nervous
      system germinal tumors.
AB  - We evaluated 79 patients of whom 62 survived treatment for intracranial germinal
      tumors between 1964 and 1992. The survivors were assessed for their Karnofsky
      scores and intellectual and reproductive functions to verify factors associated
      with better prognosis. Thirty-one tumors were pineal, 17 were suprasellar, and
      ten were in the basal ganglia. These included 50 germinomas, five teratomas, and
      seven tumors of extra-embryonic origin producing alpha-fetoprotein or human
      chorionic gonadotropin. Although patients with germinoma or benign teratoma had
      better Kaplan-Meier survival rates than those with extra-embryonic origin tumors,
      the mean Karnofsky scores of the survivors did not differ significantly among the
      three histologic groups. On the other hand, although survival rates did not
      differ significantly among different tumor site groups, the mean Karnofsky score
      of the pineal group was higher than that of the suprasellar or basal ganglia
      group. Intellectual and reproductive functions were severely affected in the
      basal ganglia and suprasellar tumor groups, respectively. The Karnofsky score of
      survivors treated after 1977 was higher than for those treated before 1977. The
      score of patients who received less than 55 Gy irradiation was better than those
      who received more than 55 Gy. No patient who received less than 45 Gy developed a
      recurrence, suggesting that a lower dose may suffice for pure germinomas. Tumors
      of extra-embryonic origin, however, should be treated with combined chemotherapy
      to minimize subsequent irradiation. Factors affecting survivors' capabilities are
      discussed.

PMID- 8310395
TI  - Ocular tuberculosis.
AB  - In recent years tuberculosis has reemerged as a serious public health problem,
      raising the possibility that tuberculous eye disease may also become more
      prevalent. The predominant route by which tubercle bacilli reach the eye is
      through the bloodstream, after infecting the lungs. The pulmonary loci might not
      be evident clinically or radiographically. The most common manifestation of
      ocular tuberculosis in patients with pulmonary tuberculosis is choroiditis.
      Retinal periphlebitis is rarely caused by direct invasion of the retina by
      tubercle bacilli. Retinal tuberculosis is usually, but not always, secondary to
      an underlying choroiditis. Tuberculoprotein hypersensitivity may have a role in
      the pathogenesis of phlyctenulosis and Eales' disease. Both ocular and orbital
      tuberculosis are usually unilateral. Skin testing should be performed in selected
      patients based on the clinical presentation and/or a history of exposure to
      tuberculosis. The specificity of the PPD skin test for Mycobacterium tuberculosis
      increases with larger skin reactions and with a history of exposure to an active
      case of tuberculosis. Because of the potential for serious drug toxicities,
      empiric treatment with antituberculous chemotherapy should be reserved only for
      those cases that have an identifiable risk of tuberculous disease.

PMID- 8310396
TI  - Duane's retraction syndrome.
AB  - Duane's retraction syndrome (DRS) has been a recognized clinical entity for
      nearly a century. It is a clinically well described ocular disorder consisting of
      retraction of the globe with narrowing of the lid fissure in attempted adduction,
      frequent abduction deficiency with variable limitation to adduction, and upshoot
      and/or downshoot of the affected eye on adduction. Among strabismus patients the
      incidence of DRS is probably not more than 5%. Most cases are sporadic, but
      familial cases have been estimated at 10% by most authors. Numerous theories
      concerning the etiology and pathogenesis of DRS have been proposed, including
      agenesis of the abducens nucleus, but the majority of investigators concur that
      the characteristic findings are best explained by a paradoxical innervation of
      the lateral rectus muscle, which subsequently causes a cocontraction of the
      horizontal rectus muscles. The frequent association of DRS with other congenital
      anomalies suggests a teratogenic event occurring between the fourth to eighth
      week of gestation as an etiological factor. In this review historical aspects and
      theories of the syndrome are studied and statistical data are compiled and
      analyzed. Clinical features, differential diagnoses and variants of the syndrome
      are examined. Testing and treatment objectives are discussed.

PMID- 8310397
TI  - Wound healing in response to keratorefractive surgery.
AB  - Over one million Americans have undergone refractive keratoplasty since the
      introduction of radial keratotomy into the United States in 1978. There are now a
      number of alternative techniques available for reshaping the corneal surface to
      alter ocular refractive errors. Numerous technologic advances in the past decade
      now enable us to perform these procedures in a safer and more reliable fashion.
      The ability to control precisely the refractive outcome, however, continues to
      elude us and appears to be limited, in part, by interindividual variability in
      the wound healing response. Presently, we review the corneal wound healing
      response to various keratorefractive approaches and suggest some interventional
      strategies which might enable us to modulate more precisely our refractive
      results.

PMID- 8310398
TI  - Gaze-induced strabismus.
AB  - A 20-year-old woman with a past history of a sinonasal undifferentiated carcinoma
      involving the skull base and cavernous sinus, previously treated with surgery and
      radiation therapy, presented with intermittent horizontal diplopia induced by
      gaze to the right side. The gaze in the direction of the action of the right VI
      nerve produced sustained contraction of the right lateral rectus and an
      exodeviation increasing on left gaze. Ocular neuromyotonia involving the right VI
      nerve was believed to be secondary to the patient's previous radiation therapy.
      The discussants review the prior literature regarding ocular neuromyotonia
      involving the III, IV and VI cranial nerves, its relationship to prior radiation
      therapy, and possible modes of therapy including the use of Carbamazepine.

PMID- 8310399
TI  - The United States' health care system: problems and solutions.
AB  - The problems facing the U.S. health care system are not new; they have been
      discussed for the last 60 years. The problems have not been solved because, due
      to fears of government involvement, we have been reluctant to impose central
      planning and management on the system. Reliance on the free market and fee-for
      service reimbursement to allocate health resources, to contain costs and to
      determine who has health insurance has failed. The result is that the U.S. spends
      more per capita on health services than any other country in the world, but lags
      behind many other countries on such health indicators as life expectancy and
      infant mortality. Several criteria for evaluating proposals for health reform are
      offered and ten such proposals are discussed. It is likely that, in the short
      run, the U.S. will adopt reforms that require the least change in the current
      system. However, these changes will not address adequately the fundamental
      problems with the system and, ultimately, major changes will have to be
      undertaken. [This article is followed by an editorial by Dr. Jonathan Trobe
      relating its concepts to the objectives set forth in the recently proposed
      Clinton Health Plan.]

PMID- 8310400
TI  - Genetics of Aicardi syndrome.

PMID- 8310401
TI  - Recurrent nerve palsy after thyroid operations--principal nerve identification
      and a literature review.
AB  - BACKGROUND: Recurrent laryngeal nerve paralysis is one of the most frequent and
      serious complications after thyroid operation. The routine dissection and
      demonstration of the recurrent nerve remain controversial. In a retrospective
      study in an endemic region, patients operated on with principal nerve
      identification were investigated for vocal paralysis. METHODS: Eight hundred and
      three consecutive goiter operations were analyzed. Because six patients had
      undergone isthmusectomies only, the recurrent laryngeal nerves were at risk in
      797 operations. For 736 patients the surgical procedure was primary for benign
      disease, for 40 patients the operation was secondary for recurrent goiters, and
      21 patients underwent operation for thyroid cancer. All patients underwent
      preoperative and postoperative laryngoscopic examination of the vocal cords by an
      ear, nose, and throat specialist. RESULTS: Rate of primary postoperative vocal
      cord paralysis was 3.6%, and the permanent palsy rate was 0.5% with a recurrent
      laryngeal nerve recovery rate of 86%. In a literature survey, reports with
      identification of the recurrent nerve had significantly lower primary and
      permanent palsy rates when compared with reports without obligatory
      identification of the nerve (p < 0.01). CONCLUSIONS: Our results and those of
      reports in the literature indicate that recurrent nerve paralysis is a less
      frequent complication when the nerve is identified.

PMID- 8310402
TI  - Immunologic assessment of host defense impairment in patients with septic
      multiple organ failure: relationship between complement activation and changes in
      neutrophil function.
AB  - BACKGROUND: The pathogenesis of gram-negative sepsis-induced multiple organ
      failure (MOF) remains to be elucidated. METHODS: Blood samples were obtained from
      eleven patients with septic MOF, three patients with sepsis, three patients who
      underwent operation, and three healthy volunteers. In these patients the
      relationship between changes in polymorphonuclear neutrophil (PMN) function and
      complement activation was investigated. RESULTS: PMNs from patients with sepsis
      exhibited enhanced endothelial cell adhesion, enhanced chemotaxis, increased
      oxygen radical generation, and increased lysosomal enzyme release. Although PMNs
      from patients with septic MOF also exhibited enhanced adhesion and chemical
      mediator production, chemotaxis was markedly depressed. Complement activation in
      septic MOF was indicated by decreases in total complement activity and complement
      component 4 (C4) and increases in C3a and C4a des-Arginine. Increases in plasma
      concentrations of circulating immunoglobulin G immune complexes and decreases in
      PMN Fc gamma R expression suggest that the classic pathway is the main pathway of
      complement activation. On the other hand, we could not detect decreases in C4 or
      increases in C4a des-Arginine in patients with sepsis, suggesting that the
      alternate pathway is the main pathway of complement activation. Increases in
      serum concentrations of the membrane attack (SC5b-9) complex also suggested that
      activated complement itself may participate in organ injury in patients with
      septic MOF. Moreover, PMN up-regulation of surface inhibitory factors of
      complement activation likely allows these neutrophils to survive and function.
      CONCLUSIONS: The combination of changes in PMN function and complement activation
      appears to be intimately associated with the pathogenesis of septic MOF.

PMID- 8310403
TI  - Sensory neuron-mediated gastric mucosal protection is blocked by cyclooxygenase
      inhibition.
AB  - BACKGROUND: Sensory neurons have been proposed to play a critical role in the
      protection of the gastric mucosa from a variety of necrotizing agents. The
      purposes of this study were (1) to investigate the effect of topical capsaicin, a
      sensory neuron stimulant, on the gastric mucosal injury caused by the topical
      application of low concentrations of bile acid and (2) to determine whether local
      neuronal blockade with topical lidocaine or cyclooxygenase blockade with systemic
      indomethacin has any effect during pretreatment with capsaicin. METHODS: Before
      injury with topical 5 mmol/L acidified taurocholate (pH 1.2) rat stomachs were
      pretreated with either vehicle or capsaicin (160 mmol/L), both with and without
      prior administration of either lidocaine (1%) or indomethacin (5 mg/kg
      subcutaneously). Injury was assessed by measuring net transmucosal ion fluxes,
      the appearance of deoxyribonucleic acid into the gastric lumen, and gross and
      histologic injury scores. RESULTS: Pretreatment with topical capsaicin
      significantly (p < 0.05) decreased bile acid-induced net luminal ion fluxes and
      luminal deoxyribonucleic acid accumulation, an effect blocked by both lidocaine
      and indomethacin. CONCLUSIONS: Thus both local neuronal blockade and
      cyclooxygenase inhibition block the protective effect of capsaicin, findings
      corroborated by gross and histologic injury analysis. This study suggests that
      sensory neurons may mediate gastric mucosal protection from bile acid injury by
      increasing synthesis of endogenous prostaglandins.

PMID- 8310404
TI  - Tube jejunostomy as an adjunct to esophagectomy.
AB  - BACKGROUND: The safety and efficacy of various methods of accessing the
      intestinal tract, including needle catheter jejunostomy, have been well
      described. This review represents an evaluation of the Witzel tube jejunostomy as
      an adjunct to esophagectomy. METHODS: The records of 523 patients who underwent
      esophagectomy for benign or malignant disease from 1976 to 1991 were reviewed.
      Each patient underwent placement of a tube jejunostomy at the time of
      esophagectomy and esophageal reconstruction. Utilization of the jejunostomy tube
      and the complications related to its placement were examined. RESULTS: The
      feeding jejunostomy was used in all patients in the initial postoperative period,
      for more than 3 weeks in 11%, and for more than 2 months in 6.9%. Major
      complications related to the jejunostomy tube occurred in 11 patients (2.1%).
      There were no fatal complications. CONCLUSIONS: Tube jejunostomy is a useful
      adjunct to esophagectomy for providing enteral nutrition during the postoperative
      period. The Witzel jejunostomy as described herein is comparable in terms of
      safety, function, and complication rate to the needle catheter jejunostomy and
      has certain technical advantages. Routine use of tube jejunostomy is recommended
      in patients undergoing esophagectomy.

PMID- 8310405
TI  - Postoperative choledochoscopy: is routine antibiotic prophylaxis necessary?--A
      prospective randomized study.
AB  - BACKGROUND: Postoperative choledochoscopy-related infection has been reported in
      the literature. We performed a prospective randomized trial to investigate the
      value of antibiotic prophylaxis for the prevention of such endoscopy-related
      infection. METHODS: In a 2-year period from 1990 to 1991, 84 patients with
      biliary lithiasis were included in the study and randomized. Forty-four patients
      received antibiotic prophylaxis (1 gm cephalothin intravenously 30 minutes before
      the procedure and 500 mg cephalexin orally every 6 hours for 3 days afterward).
      Forty patients in the control group did not receive any antibiotics. RESULTS:
      There was no significant difference between the groups in age, sex, preprocedure
      liver function, serum amylase level, white cell count, and duration of the
      procedure. The results of bacteriologic studies of the bile were also comparable
      in the two groups. One patient in the control group had transient chill and fever
      after the procedure. Two patients in the antibiotic group and one patient in the
      control group had mild abdominal pain. Mild hemobilia was noted in one patient in
      the antibiotic group. These complications were treated conservatively without any
      event. No difference was evident in the complications and the success of
      postoperative choledochoscopy between the two groups. CONCLUSIONS: This
      prospective randomized study showed that routine antibiotic prophylaxis for
      postoperative choledochoscopy may be not necessary in selected conditions.

PMID- 8310406
TI  - Mechanisms of columnar metaplasia and squamous regeneration in experimental
      Barrett's esophagus.
AB  - BACKGROUND: This study examined the effect of the lower esophageal milieu on the
      healing of a mucosal defect. METHODS: With a canine model a mucosal defect was
      created in the lower esophagus, and acid reflux was promoted by a cardioplasty
      and pentagastrin injection in 10 animals. At 3 months the regenerated mucosa was
      excised and underwent histologic examination. Six of these animals underwent an
      antireflux procedure, had their acid secretion suppressed, and were followed up
      for a further 3 months, at which time they were killed and the entire esophagus
      underwent histologic examination. RESULTS: When reflux was stimulated, healing of
      the mucosal defect was by columnar epithelium alone in seven of 10 animals. After
      reflux control in six animals healing was again by columnar epithelium, but in
      all six cases islands of squamous epithelium occurred. Histologic examination
      showed both types of regenerating epithelium to be in continuity with the ducts
      of the esophageal glands, lined in their proximal two thirds by columnar and in
      their distal one third by squamous cells. CONCLUSIONS: It is suggested that the
      type of regenerating epithelium is determined by the depth of injury to mucosa or
      gland ducts. If both cell types survive, a mixed pattern of regeneration may
      occur, but columnar repair will usually predominate because of its more rapid
      turnover. If the squamous cells of the mucosa and ducts are destroyed, however,
      repair will be by columnar epithelium alone.

PMID- 8310408
TI  - Pathophysiologic role of endothelin-1 in renal function in rats with endotoxin
      shock.
AB  - BACKGROUND: We hypothesized that endothelin-1 (ET-1) is an important mediator in
      renal dysfunction under septic conditions. This study clarified the
      pathophysiologic role of ET-1 in renal function under conditions of surgical
      stress, especially sepsis. METHODS: We investigated the correlation between ET-1
      levels and renal function and the effect of anti-ET-1 antibody (AwET-1N40) on
      renal function in a septic shock rat model. RESULTS: The plasma ET-1 level
      increased significantly at 30 minutes and remained significantly elevated for 24
      hours, reaching a peak (195 +/- 24.4 pg/ml) 3 hours after the endotoxin
      (lipopolysaccharide derived from Escherichia coli) injection. Increases in plasma
      creatinine concentration and blood urea nitrogen (BUN) level and decreases in
      urine volume and urinary sodium excretion were also observed in the early phase
      after endotoxin injection. The plasma creatinine concentration and the plasma ET
      1 level increased significantly at 30 minutes, reached a peak at 3 hours, and
      then decreased. Anti-ET-1 antibody administration (5 nmol/kg body, four times
      intravenously) decreased plasma creatinine concentration and BUN level and
      increased urine volume and urinary sodium excretion 3 hours after endotoxin
      injection (creatinine, p = 0.07; BUN, p < 0.05; urine volume, p < 0.01; urinary
      sodium excretion, p < 0.01; anti-ET-1 vs shams). CONCLUSIONS: These results
      suggest that the increase in endogenous ET-1 induced by sepsis plays an important
      role in renal dysfunction in the septic state.

PMID- 8310407
TI  - Role of B72.3 iodine 125-labeled monoclonal antibody in colorectal cancer
      detection by radioimmunoguided surgery.
AB  - BACKGROUND: Radioimmunoguided surgery (RIGS) by means of radiolabeled monoclonal
      antibodies and a probe has been reported to be useful in recognizing subclinical
      tumor deposits during operation. Aim of this study was to understand the limits
      of this technique and to assess the potential diagnostic use of RIGS in
      colorectal cancer surgery. METHODS: Monoclonal antibody B72.3 reacting with TAG
      72 antigen, labeled with iodine 125, was injected in 32 patients with primary
      tumors and in 22 patients with recurrent colorectal cancer. One hundred thirty
      three suspected tumor sites were evaluated during operation by means of probe and
      resected with immunohistochemistry as control. RESULTS: Primary tumor sites were
      localized by RIGS in 60% of cases, and recurrent sites were localized in 82% of
      cases. There was a significant correlation both for primary (p < 0.001) and
      recurrent (p < 0.001) tumor sites between intraoperative RIGS findings and TAG 72
      tumor antigen expression. Results obtained with the probe were instrumental in
      modifying the surgical approach in six (27%) of 22 patients with recurrences,
      allowing the removal of tumor masses that would otherwise have been overlooked.
      CONCLUSIONS: The results of RIGS seems to be encouraging in terms of clinical
      use. The potential high diagnostic resolution appears to improve surgical
      ablation of colorectal cancer, especially in patients with recurrent cancer or
      suspected recurrent tumors who have negative results for intraabdominal disease
      by all other roentgenographic criteria with rising carcinoembryonic antigen or
      TAG 72 antigen levels.

PMID- 8310409
TI  - L-arginine stimulates host defenses in patients with breast cancer.
AB  - BACKGROUND: The amino acid L-arginine is known to have immunostimulatory effects
      in animals and healthy human volunteers. We have studied the effect of dietary
      supplementation with L-arginine (30 gm/day for 3 days) on host defenses in
      patients with breast cancer. METHODS: Mitogenic responses of peripheral blood
      lymphocytes to concanavalin A, phytohemagglutinin, and pokeweed mitogen and
      phenotype analysis of lymphocyte subsets and activation markers were assessed
      before and after 3 days of L-arginine supplementation. The effect of L-arginine
      supplementation on natural killer and lymphokine-activated killer cell
      cytotoxicity and serum levels of the cytokines interleukin-1 beta and 2,
      interferon-gamma, and tumor necrosis factor-alpha were also measured. RESULTS: L
      arginine significantly increased lymphocyte mitogenic reactivity to concanavalin
      A, phytohemagglutinin, and pokeweed mitogen (mean percentage increases: 64% [p <
      0.001], 65% [p < 0.001], and 48% [p < 0.05], respectively). Natural killer and
      lymphokine-activated killer cell cytotoxicity was also significantly enhanced
      after L-arginine intake (mean percentage increase, 81% and 107% [p < 0.001]).
      However, no corresponding increase in circulating CD16+ and CD56+ cells was
      obtained: Arginine supplementation did not increase the level of serum cytokines.
      CONCLUSIONS: Dietary supplementation with L-arginine in patients with breast
      cancer significantly enhances host defenses and therefore may have a role in
      adjuvant treatment.

PMID- 8310410
TI  - Induction of tumor necrosis factor in severe acute pancreatitis and its
      subsequent reduction after hepatic passage.
AB  - BACKGROUND: Tumor necrosis factor (TNF) is rapidly gaining recognition as one of
      the early, critical mediators of several inflammatory conditions, most notably
      endotoxic shock. The purposes of this study were to determine whether TNF levels
      are raised in severe acute pancreatitis, thus pointing to its role as a potential
      mediator of the inflammatory process, and to determine the possible sites of
      production and uptake. METHODS: TNF levels were measured during a 2-hour period
      in a rat model of acute pancreatitis by using an antegrade infusion of artificial
      bile. TNF levels were measured with a bioassay. RESULTS: TNF levels increased
      proportionately with time and serum amylase level, reaching a mean value of 2700
      pg/ml at 2 hours compared with sham operated rats (mean, 125 pg/ml) (p < 0.001).
      TNF levels in nonoperated controls were undetectable. These measurements were
      found to be independent of endotoxin production. In addition, selective sampling
      from the portal vein, hepatic vein, and femoral artery showed hepatic degradation
      of TNF (p < 0.005), indicating that the liver may play an important role in
      protecting the host from multiple organ failure. CONCLUSIONS: Our results showed
      that TNF levels are elevated in acute pancreatitis and may suggest a role for
      this cytokine in the pathogenesis of the disease.

PMID- 8310411
TI  - Effects of gastric fundusectomy and antrectomy on gallbladder epithelial
      proliferation in the hamster.
AB  - BACKGROUND: Exogenous administration of cholecystokinin or its analog cerulein
      induces epithelial hyperplasia in the mouse gallbladder. The effects on the
      gallbladder of resectional surgery of the stomach with hormonal consequences are
      not known. METHODS: The effects of gastric fundusectomy and antrectomy on
      proliferation and growth of the gallbladder epithelium were studied in male
      Syrian golden hamsters during periods of 5 and 25 days. Sham-operated animals
      served as controls. RESULTS: Basal plasma gastrin concentrations were
      significantly increased after fundusectomy and significantly decreased after
      antrectomy, whereas basal plasma cholecystokinin concentrations were not
      significantly affected. Five days after fundusectomy, there was a significant
      increase in the tritiated thymidine DNA labeling index of gallbladder epithelial
      cells. On day 25, the gallbladder weight and total number of epithelial cells
      were significantly increased after fundusectomy. Antrectomy significantly
      decreased the gallbladder weight on day 25, whereas the labeling index and total
      number of epithelial cells were not significantly affected on days 5 and 25.
      CONCLUSIONS: These results suggest that gastric fundusectomy at least transiently
      induces gallbladder epithelial hyperplasia and hypertrophy in the hamster.
      Although achlorhydria and hypergastrinemia are prominent features, the actual
      mechanism behind this effect of fundusectomy on the gallbladder needs further
      clarification.

PMID- 8310412
TI  - Effect of omentopexy on wound healing of the extensively detached and anastomosed
      canine trachea.
AB  - BACKGROUND: To examine the beneficial effect of omentopexy for tracheal
      anastomosis after extensive detachment that may cause impairment of the blood
      supply, the time course of tracheal wound healing was studied experimentally.
      METHODS: Circumferential resection of the trachea for three cartilage rings (nos.
      11, 12, 13) and end-to-end anastomosis of the trachea were performed in 66
      mongrel dogs, which were allocated to three groups (n = 22 in each). In the
      detached group, the trachea was entirely mobilized and isolated from the
      surrounding tissue for a length of 25 cartilage rings. In the wrapped group,
      omentopexy was added for the anastomosed site. In the control group, the same
      anastomosis was performed without omentopexy or detachment. The tracheal tissue
      blood flow was measured with a laser Doppler flow meter at the anastomosed site,
      and the tensile strength was determined with a tensiometer. RESULTS: All groups
      showed significant decreases in the blood flow on day 3, compared with the
      preoperative values, and increases stepwise from day 7 to day 21. On days 3, 7,
      and 14 the tissue blood flow was significantly (p < 0.01) higher in the wrapped
      group than in the detached group, although on day 21 it did not differ
      significantly among the three groups. The tensile strengths of the cartilaginous
      and membranous portions were significantly (p < 0.05) higher in the wrapped and
      control groups than in the detached group. On day 21, no significant intergroup
      differences were observed for this parameter. In the wrapped group and in the
      control group, the capillary network at the anastomosed site was well developed
      on day 7, and the tracheal mucosal epithelium was well regenerated on day 21
      without granulation formation. CONCLUSIONS: This study showed that omentopexy at
      the anastomosed site of an extensively detached trachea provided adequate wound
      healing caused by rapid recovery of the tissue blood flow.

PMID- 8310413
TI  - Thyroid surgery in untreated severe hyperthyroidism: perioperative kinetics of
      free thyroid hormones in the glandular venous effluent and peripheral blood.
AB  - BACKGROUND AND METHODS: It is generally believed that thyroid surgery in Graves'
      disease requires a euthyroid state to avoid thyrotoxic reactions. We carried out
      a prospective study on 23 patients who had severe hyperthyroidism with free
      thyroid hormone concentrations (fT3 or fT4) exceeding the upper normal boundary
      by 300% or more and who were not pretreated with thyrostatic agents. We
      determined hormone levels during operation in the thyroid venous effluent before
      and after surgical trauma and monitored their postoperative elimination kinetics.
      RESULTS: The concentration of fT3 and fT4 in the venous effluent of the
      hyperactive gland did not exceed the peripheral levels. Surgery did not induce
      any intraoperative or postoperative increase in fT4 or fT3, whereas thyroglobulin
      concentrations rose sharply. Both fT4 and fT3 followed biphasic elimination
      kinetics, and a significant decline of circulating free hormone concentrations
      was measurable within the first postoperative hour. CONCLUSIONS: Contrary to
      widely held assumptions, the surgical trauma does not stimulate the release of
      thyroid hormones. Hence this mechanism cannot account for the postoperative
      development of thyroid storm. Our observations imply that immediate operation
      should generally be considered for the emergency treatment of an imminent thyroid
      storm.

PMID- 8310414
TI  - Hemoglobin blood substitutes in extended preoperative autologous blood donation:
      an experimental study.
AB  - BACKGROUND: The risks of homologous blood transfusion have stimulated interest in
      developing possible alternatives. In this study we examined the efficacy of using
      a hemoglobin-derived blood substitute to augment and extend preoperative
      autologous blood donation. METHODS: In an ovine model, two experimental groups (n
      = 6 each) of animals donated either 45% or 80% or more of calculated blood
      volume, which was replaced with a polymerized bovine hemoglobin solution. Two
      control groups (n = 6 each) either did not donate or donated 45% of calculated
      blood volume, which was replaced with a 6% hetastarch solution. Twenty-four hours
      after blood donation, sheep underwent a measured surgical stress with
      standardized intraoperative blood loss; donated blood was reinfused. RESULTS:
      Extended autologous blood donation and replacement with this blood substitute
      were efficacious in supporting oxygen consumption; there was no systemic
      toxicity. After the postoperative replacement of autologous blood, animals that
      donated 80% or more of red cell mass exhibited overall blood conservation with a
      final hematocrit of 25.7% +/- 3.6%, compared with 20.5% +/- 2.0% (p < 0.05) and
      with 21.5% +/- 1.1% (p < 0.05) in both control groups. CONCLUSIONS: This study
      suggests that the benefits of a blood substitute can be combined with autologous
      blood donation to (1) safely increase the amount of autologous blood donated
      while supporting oxygen consumption, (2) avoid the need for advanced preoperative
      donation, and (3) decrease the need for homologous blood transfusion.

PMID- 8310415
TI  - A new procedure for abdominal wound closure after pediatric liver
      transplantation: the "sandwich" technique.
AB  - Primary wound closure cannot always be achieved after pediatric liver
      transplantation (LTx). This may be due to lack of intraabdominal space from
      postanhepatic small bowel edema or oversized grafts despite partial LTx. For
      those instances we developed the "sandwich" technique. This procedure
      incorporates advantages of previous techniques with some additional advantages
      described herein. Use of polyglactin 910/silicone meshs in a sandwich fashion
      allows for one-stage permanent abdominal closure without major loss of body
      plasma fluids after pediatric LTx. So far our clinical experience with this
      technique has been very satisfying.

PMID- 8310416
TI  - Primary parathyroid hyperplasia associated with thyroid hemiagenesis and agenesis
      of the isthmus.
AB  - BACKGROUND: Congenital thyroid anomalies can be caused by abnormal descent or
      agenesis of part of the thyroid gland. Agenesis of the thyroid gland may involve
      one or both lobes of the gland, with or without isthmus, and is very rare.
      Congenital thyroid anomalies have been reported to be associated with thyroid
      diseases (hyperthyroidism, adenomatous goiter, and cancer) but not with
      parathyroid diseases. METHODS: Case reports of two patients describe the methods
      used. RESULTS: We report two patients with hyperparathyroidism and congenital
      thyroid anomalies. One patient had a left thyroid lobe hemiagenesis and the other
      patient had agenesis of the thyroid isthmus. Both patients had primary
      hyperparathyroidism caused by parathyroid hyperplasia and were treated by
      subtotal parathyroidectomy. The parathyroid glands and recurrent laryngeal nerves
      were in their usual positions despite the abnormal development of the thyroid
      glands. CONCLUSIONS: When thyroid hemiagenesis or isthmus agenesis is found in
      patients undergoing parathyroidectomy for hyperparathyroidism, parathyroid
      hyperplasia should be suspected. If parathyroid hyperplasia is present, subtotal
      parathyroidectomy and bilateral thymectomy are recommended. The parathyroid
      glands and the recurrent laryngeal nerves can be found in their usual locations.

PMID- 8310417
TI  - Aortobronchial fistula: report of three cases and review of the literature.
AB  - BACKGROUND: Aortobronchial fistula is uniformly fatal if not treated surgically.
      The aim of this study is to report three new cases and to discuss cause, clinical
      findings, surgical approaches, and results. METHODS: All three patients with
      massive hemoptysis underwent operation in emergency situation. The procedure
      performed were a Bentall operation for a false aneurysm of the ascending aorta 10
      years after the correction of an acute dissection, a Dacron graft replacement for
      a mycotic aneurysm of the descending aorta, and an extraanatomic bypass between
      ascending and celiac aortas for a false aneurysm 14 years after the correction of
      an isthmic coarctation. RESULTS: The patient with the mycotic aneurysm died of
      paraplegia and septicemia after operation. The other two were without symptoms
      after 2 years of follow-up. CONCLUSIONS: The diagnosis should be considered in
      any patient with minor or major hemoptysis and prior history of thoracic aortic
      operation. Aortography and thoracic computed tomographic scan are the main
      investigations for diagnosis. Direct approach or extraanatomic bypass have the
      same results with a survival rate of 76% in the recent literature. Early
      diagnosis and emergency surgery are the two predictive factors for good results.

PMID- 8310418
TI  - Thyroid reexploration.

PMID- 8310419
TI  - Gunshot wounds: a familial disease.

PMID- 8310420
TI  - Clinical aspects of restorative treatment in the primary dentition.
AB  - The failure rate of restorative treatment in primary teeth was studied in a
      cohort of children born in 1981 and related to caries diagnosis, prevalence and
      distribution on different tooth surfaces, and compared with a cohort of children
      born in 1971. Concurrently, the longevity of composite resin in modified Class 2
      cavities in primary molars was followed up and the resistance of deciduous and
      permanent enamel to acid adjacent to composite resin and glass polyalkeonate
      cement (GPA) was tested in vitro. From the 70s to the 80s, diagnostic methods
      changed and the examination intervals were prolonged. The number of bite-wing
      radiographs was halved and the participation in all six annual examinations
      decreased from 89% to 32%. Caries prevalence increased from 1.1 ds in 3-year-olds
      to 6.3 ds in 8-year-olds in Cohort '71 and, in the same ages, from 0.2 ds to 3.0
      in Cohort '81. In Cohort '81, an overall decline of occlusal caries was recorded.
      The distal surface of the first molars was the proximal surface most often
      affected in both cohorts. In Cohort '81, 30% had caries-free primary teeth at the
      age of 8, which can be compared with 17% in the cohort 10 years earlier. In
      Cohort '81, the proportion of replaced proximal restorations was 14% and that of
      extracted molars 2%. The corresponding figures for Cohort '71 were 17% and 4%,
      respectively. In Cohort '81, silver amalgam was used in 65% and GPA cements in
      35%. On all surfaces, silver amalgam was replaced in 22% and GPA cements in 6%.
      Composite resin in modified Class 2 cavities showed a cumulative success rate
      that declined from 86% after one year to 38% after six years. Fractures occurred
      early and recurrent caries was found from the second year of the follow-up.
      Histological investigation of these teeth disclosed bacteria subjacent to the
      fillings in 75% and recurrent caries in 58%. The restorations in teeth with
      bacterial invasion showed marginal discolouration, visible crevices or colour
      mismatch. In an acid environment, the enamel showed artificial caries lesions
      adjacent to composite resin significantly more often in primary teeth than in
      permanent teeth. No lesions were seen close to GPA fillings in primary teeth. The
      improved dental health appeared to be of greater benefit to the children and care
      providers than advances in restorative treatment. The properties of GPA cements
      seem useful in the restorative treatment of primary teeth.

PMID- 8310421
TI  - Quantitation and three-dimensional reconstruction of Ch4 nucleus in the human
      basal forebrain.
AB  - The basal nucleus of Meynert, incorporating the Ch4 group of cholinergic neurons,
      was examined in six patients with no signs of neurological abnormalities. The
      ages of the patients ranged from 20 to 80 years. Despite a number of descriptions
      of these neurons, few age-related studies have been dedicated to the analysis of
      the entire anteroposterior extent of the nucleus. Staining with cresyl violet and
      acetylcholinesterase histochemistry, alone or in combination, was used to
      identify the cytoarchitectural organization of the Ch4. Computer-assisted
      morphometry was used for three-dimensional visualization and quantitation. The
      three-dimensional computer reconstructions revealed a continuous ribbon of
      neurons with a highly variable density. Four distinct subregions could be clearly
      identified in all cases by their cytoarchitecture and cellular morphology,
      although these subgroups were different to those previously described. There were
      no quantitative differences between the hemispheres in volume, density or cell
      number of the Ch4, although equivalent levels varied in area and density. The
      measures were similar in all cases with the exception of the case aged 80 years
      old. The data demonstrate individual variability in three dimensions and confirm
      previous studies that found only a mild decline of the Ch4 in old age.

PMID- 8310422
TI  - Evidence for the cholinergic nature of C-terminals associated with subsurface
      cisterns in alpha-motoneurons of rat.
AB  - C-terminals can be distinguished at the ultrastructural level from other types of
      nerve endings on motoneurons by their prominent and regularly occurring
      postsynaptic specializations termed subsurface cisterns (SSC). We have previously
      shown (Yamamoto et al., 1991) that an antibody directed against a sequence within
      the gap junction protein connexin32 immunolabels these motoneuronal SSCs and can
      therefore serve as a immunohistochemical tool to visualize indirectly the
      location of C-terminals on motoneurons at the light microscope level. Here we
      have used this anti-SSC antibody in combination with antibodies against choline
      acetyltransferase (ChAT) and acetylcholinesterase (AChE) to determine whether C
      terminals on motoneurons contain these cholinergic enzyme markers. In sections at
      all major spinal cord levels and in several cranial motor nuclei examined,
      motoneuronal cell bodies and their proximal dendrites were studded with large
      ChAT-immunoreactive (ChAT-IR) boutons. Boutons having a similar distribution and
      appearance on motoneurons were also immunolabeled for AChE. In addition,
      motoneurons were surrounded by a dense plexus of AChE-immunoreactive (AChE-IR)
      varicose fibers and fine preterminal axons. In double-labeled sections, AChE-IR
      boutons corresponded to those immunolabeled for ChAT. In sections processed for
      simultaneous immunofluorescence detection of ChAT and SSCs, ChAT-IR boutons were
      very often found in apposition to immunolabeled SSCs. In sections processed for
      simultaneous labeling of AChE and SSCs. AChE-IR boutons were again frequently
      seen abutting labeled SSCs. These results provide the first strong evidence at
      the LM level that a large proportion, if not the entirety, of C-terminals are
      cholinergic and show that these terminals consist in part of relatively large
      varicosities along highly varicose axons that form en passant type contacts on
      motoneurons. At the same time, our results substantially narrow possibilities
      regarding the as yet undetermined source of C-terminals, which can now be
      considered to originate from cholinergic neurons, such as those located in the
      brainstem and/or the spinal cord.

PMID- 8310423
TI  - Chronic repeated cocaine administration alters basal and opioid-regulated
      adenylyl cyclase activity.
AB  - Repeated daily cocaine injections have been shown to alter mu-opioid receptor
      densities in the caudate putamen and nucleus accumbens of rat brain (Unterwald et
      al., 1991, 1992). Adenylyl cyclase activity was measured in rat rostral caudate
      putamen and nucleus accumbens following repeated cocaine administration to
      determine the functional consequences of cocaine-induced opioid receptor changes.
      Male Fischer rats were injected daily for 14 days with saline or cocaine HCl (30
      or 45 mg/kg/day, i.p.) in three equal doses at 1-hr intervals. Basal adenylyl
      cyclase activity and the effects of the selective mu- and delta-opioid agonists
      [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO) and [D-penicillamine2,D
      Penicillamine5]enkephalin (DPDPE), respectively, on adenylyl cyclase activity
      were examined 30 min after the last injection using a cAMP radioligand binding
      assay in crude membrane preparations. Basal adenylyl cyclase activity was 49% and
      34% lower in the caudate putamen of animals treated with 30 and 45 mg/kg/day of
      cocaine, respectively, as compared to those receiving saline injections. Basal
      adenylyl cyclase activity was unchanged in the nucleus accumbens following
      cocaine treatment. DAMGO and DPDPE each maximally inhibited approximately 25% and
      30%, respectively, of basal adenylyl cyclase in the caudate putamen and nucleus
      accumbens of saline-injected animals. Administration of cocaine attenuated the
      ability of DPDPE to inhibit adenylyl cyclase in both brain regions, but had no
      effect on the efficacy or potency of DAMGO for inhibiting adenylyl cyclase
      activity. These results suggest that chronic, repeated cocaine administration
      results in a selective impairment of delta-opioid receptor-mediated effector
      function in the caudate putamen and nucleus accumbens.

PMID- 8310424
TI  - Muscarinic potentiation of excitatory amino acid-evoked dopamine release in
      mesencephalic cells: specificity for the NMDA response and role of intracellular
      messengers.
AB  - Of the five cloned muscarinic receptor subtypes, dopamine (DA) neurons in the
      substantia nigra and ventral tegmental areas have been shown to be selectively
      enriched with the mRNA for the m5 subtype, suggesting that muscarinic modulation
      of DA neurons may have a distinct pharmacology. In the present study we have used
      dissociated cell cultures of fetal rat ventral mesencephalon to characterize
      muscarinic modulation of DA neurons. [3H]DA release stimulated by activation of N
      methyl-D-aspartate (NMDA) receptors was potentiated by carbachol, a mixed
      muscarinic-nicotinic agonist, and by oxotremorine-M, a muscarinic agonist.
      Neither carbachol nor oxotremorine-M had an effect on [3H]DA release evoked by
      the non-NMDA agonists, kainate or quisqualate. A nicotinic agonist, DMPP, had no
      effect on NMDA-stimulated release. Potentiation of NMDA-stimulated [3H]DA release
      by oxotremorine-M was inhibited by the broad spectrum muscarinic antagonist, QNB,
      and by low concentrations of a putative M1 antagonist, pirenzepine, while much
      higher concentrations of a purported M2 antagonist, AF-DX 384, were required to
      reverse the oxotremorine-M effect. The muscarinic antagonist, 4-DAMP, was active
      in a concentration range between that required for pirenzepine and AF-DX 384.
      Further experiments examined intracellular messenger mechanisms coupled to the
      muscarinic receptors modulating NMDA-stimulated [3H]DA release. In contrast to
      oxotremorine-M, two muscarinic agents with only weak partial agonism with respect
      to phosphoinositide turnover, pilocarpine and arecoline, had no effect on NMDA
      stimulated [3H]DA release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8310425
TI  - Autoradiographic localization of [125I-Tyr8]-bradykinin receptor binding sites in
      the guinea pig spinal cord.
AB  - The present study aimed to localize and characterize [125I-Tyr8]-BK binding sites
      in all major segments of the guinea pig spinal cord using in vitro quantitative
      receptor autoradiography. [125I-Tyr8]-BK specific binding sites were localized
      predominantly in superficial layers of the dorsal horn, with lamina II depicting
      the highest labelling. The density of specific binding in laminae I and III was
      moderate, whereas in other areas, i.e., laminae IV-X, lower amounts of labelling
      were noticed. The B2 receptor antagonists D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-BK (Hoe
      140), D-Arg[Hyp3,D-Phe7,Leu8]-BK, Tyr0,D-Arg[Hyp3,D-Phe7,Leu8]-BK, D-Arg[Tyr3,D
      Phe7,Leu8]-BK, D-Arg[Hyp2,Thi5,8,D-Phe7]-BK, D-Arg[Hyp3,Leu8]-BK and D
      Arg[Hyp3,Gly6,Leu8]-BK as well as unlabelled [Tyr8]-BK inhibited [125I-Tyr8]-BK
      binding with respective Ki values of 0.04, 12.4, 23.4, 34.5, 43.5, 33.5, 23.0,
      and 0.6 nM while B1 related molecules (Tyr0,des-Arg10-kallidin and [Leu8]-des
      Arg9-BK) did not significantly inhibit [125I-Tyr8]-BK binding up to micromolar
      concentrations. These results indicate that the specific [125I-Tyr8]-BK binding
      sites present in the guinea pig spinal cord belong to the B2 receptor subtype.
      The high density of B2 binding sites in the substantia gelatinosa provides an
      anatomical evidence in favour of a role for BK as a modulator of nociceptive
      information.

PMID- 8310426
TI  - Dopamine transporter mutants selectively enhance MPP+ transport.
AB  - MPP+ (1-methyl-4-phenylpyridinium), a dopaminergic neurotoxin that provides the
      best available experimental model of Parkinson's disease, is selectively
      concentrated in dopamine neurons by the dopamine transporter (DAT). DAT also
      serves as a primary recognition site for cocaine. To help define selective
      molecular mechanisms by which MPP+ uptake occurs, we have tested dopamine
      transporters mutated in several residues for their abilities to accumulate
      dopamine and MPP+, and to bind a cocaine analog. Mutants in DAT 7th and 11th
      hydrophobic putative transmembrane domains increase MPP+ uptake velocity and
      affinity (1/KD), respectively. These mutations exert much more modest effects on
      dopamine uptake and have little impact on cocaine analog binding. These findings
      provide the first example of mutations that enhance transport and identify
      specific DAT amino acids selectively involved in neurotoxin uptake. They may also
      have implications for the feasibility of developing drugs that could specifically
      block accumulation of Parkinsonism-inducing neurotoxins.

PMID- 8310427
TI  - Local infusion of the selective 5HT-1b agonist CP-93,129 facilitates striatal
      dopamine release in vivo.

PMID- 8310428
TI  - What are purchasers looking for in managed care quality?
AB  - Spurred by competition and the growth of managed care, providers are seeking new
      approaches for satisfying the needs of health care purchases. Increasingly, these
      purchasers are focusing on the value of managed care arrangements, especially the
      degree to which they manage quality. Underlying the emerging focus on quality are
      concerns about "undercare," potential legal liability, and the economics of
      quality. Purchasers are sensitive to the quality of service and the experience of
      their patients, as well as the clinical quality of the care they receive, and
      many employers are now engaged in a systematic effort to assess both of these
      dimensions of quality. The emergence of national data banks, practice standards,
      and accreditation programs offers additional tools for strengthening provider
      accountability for quality.

PMID- 8310429
TI  - Managed care programs: an employer perspective.
AB  - Throughout the 1980s, employers made many health care benefit plan modifications
      that were directed toward containing costs. This chapter discusses potential
      managed care program changes that may occur in the coming years. Specifically
      reviewed are partnerships between employers and managed care entities; possible
      features of the next generation of managed are plans; and dimensions of a cost
      benefit analysis that employers could use to gauge the cost-effectiveness of
      future plan changes.

PMID- 8310430
TI  - Legal considerations in managed care contracting.
AB  - Managed health care systems are created primarily through contracting. Although
      contracts with managed care organizations, such as health maintenance
      organizations, are often presented to providers as non-negotiable, this chapter
      discusses basic contract terms that are frequently negotiated by the parties,
      including key contract definitions, compensation, term and termination, and
      "boilerplate" provisions. The chapter also emphasizes the need for contracting
      parties to conduct precontracting due diligence and to comply with applicable
      antitrust laws in negotiating contracts with groups of independent providers.

PMID- 8310431
TI  - The evolution of decision support in a managed care organization.
AB  - As managed care organizations (MCOs) develop in the 1990s, a challenge for
      managers is the transformation of data into information. This transformation
      process is responsible for organizations developing decision support systems.
      Decision support enables an individual to combine financial analysis and
      operational data to enhance managerial decision making and strategic planning,
      and institute the closed-loop process. This system evolution will help to
      determine those MCOs that will become more adept at enhancing profitability and
      streamlining decision making.

PMID- 8310433
TI  - Establishing a physician incentive system.
AB  - The increasing complexity of managed care is changing the need for better
      information on medical costs and utilization. Because most claims systems have
      limited reporting and analysis capabilities, a better alternative is to transfer
      the data into the reporting systems described herein, in which a comprehensive
      analysis is conducted faster and at a lower cost. Virtually any type of analysis
      is possible.

PMID- 8310432
TI  - Managed care relationships from the physician's perspective.
AB  - In response to health care reform proposals as well as health plans, hospitals
      and individual physicians are affiliating into models that will favorably
      position them in the evolving managed care marketplace. The development of
      integrated delivery vehicles requires a merging of physician and hospital
      cultures. To manage this process the relationship between hospitals and
      physicians must receive the greatest attention. This chapter describes physician
      perceptions of specific aspects in the evolving managed care marketplace.
      Understanding reactions to various initiatives will enable readers to overcome
      resistance to change and improve their managed care relationships with
      physicians.

PMID- 8310434
TI  - Independent practice associations: are they viable?
AB  - As managed care systems grow along with the efforts of health care reform,
      independent practice associations (IPAs) will develop and grow. Their success is
      dependent on efficient management, enrollment, computer systems, a strong medical
      director, and case management. The IPA is an effective organization to deliver
      care through a capitated payment system.

PMID- 8310435
TI  - Specialty service contracting.
AB  - Package pricing of specific services and procedures can be an effective cost
      containment and marketing tool for payers and providers. Payers can secure fixed
      prices at discounted rates, and hospitals and physicians can retain and gain
      market share in an increasingly competitive health care market. Successful
      implementation of a package pricing strategy, however, requires a careful
      assessment of both market and operational factors. This chapter outlines how to
      identify opportunities for package pricing and how to establish rates and
      procedures.

PMID- 8310436
TI  - Administrative and operational responsibilities in contract management.
AB  - Frequently, chief financial officers or marketing executives negotiate contracts
      that are difficult if not impossible to implement. In addition, those parties
      responsible for implementing contracts are often unaware of the terms. Formal
      verbal and written communications within a health care organization will minimize
      consumer (payer and patient) displeasure, as well as alleviate internal
      frustration and stress.

PMID- 8310437
TI  - Creating an integrated health care delivery system: a regional nonprofit provider
      case study.
AB  - The development of integrated health care systems holds many pitfalls as well as
      potentials. This case study describes the development of the strategy that has
      moved the structure, mission, and vision of a health care system. It examines the
      questions of what members, payers, and providers' needs are when defined around
      the paradigm of responsibility for the health as well as the health care of a
      population. It starts by examining the background of the development of the
      strategies used by the health system during the past decade, and the
      environmental climate that has led to a redefinition of the mission and vision of
      the organization. This movement has moved the focus on acute health services to
      the development of a regional integrated health care system based on
      collaboration and on a responsibility to improve the health of those we serve
      through treatment, prevention, and education. Finally, the chapter reviews the
      options facing all of us: do we compete, collaborate, or both?

PMID- 8310438
TI  - Toxins from ascidians.
AB  - A wide range of toxins with interesting pharmacological properties have been
      isolated from ascidians. These include cyclic peptides, one of which, didemnin B,
      is undergoing clinical trials for cancer chemotherapy and is also a powerful
      immunosuppressive agent. Other classes of toxins from these organisms are
      alkaloids, macrolides, polyethers, prenylated hydroquinones and others of diverse
      chemical structure. The majority of these compounds are cytotoxic and in some
      cases the mechanisms of action have been investigated. The toxins are most likely
      used for chemical defense but the question of how the ascidians themselves escape
      the toxic actions is also not resolved.

PMID- 8310439
TI  - Effects of scorpion (Buthus tamulus) venom on neuromuscular transmission in
      vitro.
AB  - The effects of venom from the Indian red scorpion Buthus tamulus (BT) on
      neuromuscular transmission have been investigated by means of twitch tension and
      electrophysical recording techniques using isolated skeletal muscle preparations.
      On chick biventer cervicis preparations, BT (1-3 micrograms/ml) augmented the
      twitch responses to indirect, but not direct, muscle stimulation. Higher
      concentrations caused a transient augmentation followed by a large contracture
      and then a reduction in twitch height. BT at the concentrations tested caused
      little change in postjunctional sensitivity as assessed by responses to exogenous
      acetylcholine, carbachol and KCl. Tubocurarine abolished the prolonged
      contracture induced by BT (10 micrograms/ml) in the presence or absence of nerve
      stimulation. On mouse hemidiaphragm preparations, BT (3-10 micrograms/ml)
      increased the twitch responses to indirect stimulation but caused little change
      in directly stimulated preparations. On mouse triangularis sterni preparations,
      BT (3-10 micrograms/ml) increased quantal content of the evoked end-plate
      potentials (epps) by about 70%, without markedly affecting the time course and
      amplitude of miniature epps. BT also caused repetitive epps in response to single
      shock nerve stimulation. Extracellular recording of nerve terminal current
      waveforms in triangularis sterni preparations revealed that BT (10-30
      micrograms/ml) slightly reduced the amplitude of the waveform. Subsequently, BT
      induced repetitive firing of nerve endings in response to single shock
      stimulation, and eventually markedly prolonged the time course of the nerve
      terminal waveform. The effects caused by BT were different from those caused by
      iberiotoxin, the blocker of Ca(2+)-activated K+ currents, isolated from BT. The
      effects were similar to those caused by ATX-II, a toxin that delays inactivation
      of Na+ channels. However, BT and ATX-II behaved differently in the presence of K+
      channel blockers, 3,4-diaminopyridine (DAP) and tetraethylammonium (TEA). These
      results confirm that Buthus tamulus venom acts mainly prejunctionally to increase
      the release of acetylcholine. The effect of BT on the perineural waveforms
      suggests that some of its actions may be due to effects on Na+ channels at or
      near the nerve terminals; however, additional effects of K+ channels are likely.

PMID- 8310440
TI  - Activation of tissue kallikrein-kininogen-kinin system in rabbit skin by a
      fraction isolated from Phoneutria nigriventer (armed spider) venom.
AB  - Phoneutria nigriventer venom was fractionated by gel filtration followed by ion
      exchange chromatography from which 16 fractions (I-XVI) were obtained and assayed
      in rabbit skin in order to identify those responsible for the increased vascular
      permeability observed with the whole venom. The fractions, and control mediators
      (tissue kallikrein, bradykinin and histamine) were intradermally injected in male
      New Zealand white rabbits. Local oedema formation was measured as the local
      accumulation of i.v. injected 125I-human serum albumin into skin sites. Fraction
      XIII was the only fraction assayed which significantly induced oedema formation.
      Fraction XIII-induced oedema was greatly reduced by either the protease inhibitor
      aprotinin or the bradykinin B2 receptor antagonist D-Arg,[Hyp3,Thi5,8D-Phe7]-Bk,
      whereas the plasma kallikrein inhibitor soybean trypsin inhibitor failed to
      significantly affect this oedematogenic response. The kininase II inhibitor
      captopril markedly potentiated fraction XIII-induced oedema. Our results indicate
      that the increased vascular permeability induced by fraction XIII is due to local
      generation of kinins in response to tissue (but not plasma) kallikrein-kinin
      system activation.

PMID- 8310441
TI  - A unified bioscreen for the detection of diarrhetic shellfish toxins and
      microcystins in marine and freshwater environments.
AB  - Capillary electrophoresis (CE) coupled with liquid chromatography (LC)-linked
      protein phosphatase (PPase) bioassay was used to detect sensitivity both
      diarrhetic shellfish toxins and hepatotoxic microcystins in marine and freshwater
      samples. This procedure provided a quantitative bioscreen for the rapid optical
      resolution of either of these toxin families in complex mixtures such as cultured
      marine phytoplankton, contaminated shellfish and cyanobacteria (natural
      assemblages). Following detection, identified toxins were purified by an enzyme
      bioassay-guided two-step LC protocol. Using the latter approach, at least four
      microcystins were rapidly isolated from a cyanobacteria bloom (largely
      Microcystis aeruginosa) collected from a Canadian drinking-water lake, including
      a novel microcystin termed microcystin-XR, where X is a previously unidentified
      hydrophobic amino acid of peptide residue molecular mass 193 Da. The unified
      CE/LC-linked PPase bioscreen described provides a powerful capability to dissect
      multiple toxin profiles in marine or freshwater samples contaminated with either
      okadaic acid or microcystin classes of toxin.

PMID- 8310442
TI  - Identification of protein phosphatase inhibitors of the microcystin class in the
      marine environment.
AB  - Toxins produced by marine phytoplankton represent a severe global health hazard
      to humans that eat seafood and are also responsible for massive natural fish
      kills in specialized bloom situations. Tumour-promoting hepatotoxins from the
      freshwater microcystin/nodularin class were identified in Northeastern Pacific
      Ocean, Eastern Canadian and European mussels for the first time. These
      hepatotoxins were detected at biologically active levels up to three-fold higher
      than accepted quarantine levels for the diarrhetic shellfish toxin okadaic acid
      (OA), based on their activity (in microcystin-LR equivalent units) in a liquid
      chromatography (LC)-linked protein phosphatase bioassay. The presence of
      microcystins/nodularins in oceanic shellfish identifies a potentially novel class
      of intoxication which is also prevalent in other forms of marine aquatic life,
      namely sponges and fish. The widespread presence of prokaryotic microcystins and
      nodularins in the marine environment may be indicative of the importance of
      signal transduction pathways involving potent inhibition of protein phosphatases
      in early marine eukaryotes.

PMID- 8310443
TI  - Disulfide formation in reduced tetanus toxin by thioredoxin: the pharmacological
      role of interchain covalent and noncovalent bonds.
AB  - The interchain disulfide bond of tetanus toxin is known to be cleaved by reduced
      thioredoxin and by rat brain homogenate. We now show that this bond, but not the
      disulfide loop in the heavy chain of the toxin, can be restored quickly and
      completely by oxidized thioredoxin. Oxidized glutathione was at least 100 times
      less potent and less specific. Reduced tetanus toxin did not measurably (KD below
      50 nM) dissociate into its chains, as revealed by HPLC gel chromatography under
      nondenaturing conditions. Accordingly, when the reduced toxin or its recombined
      chains were injected into mice, general toxicity was diminished but not
      abolished, as compared with the native form. Inhibition of Ca(2+)-evoked
      [3H]noradrenaline release was assayed in cultured adrenomedullary cells after
      permeabilization with digitonin. Reduced two-chain tetanus toxin was as active as
      the isolated light chain in this system, and the action of the light chain was
      only slightly diminished by the addition of excess heavy chain. The results show
      that thioredoxin can both open and close the covalent bond between the chains of
      tetanus toxin, and that the reduced chains remain linked by noncovalent forces.
      The role of the thioredoxin system for reversible activation of tetanus toxin in
      vivo remains to be established.

PMID- 8310444
TI  - A thrombin-like enzyme from bushmaster (Lachesis muta stenophyrs) venom.
AB  - The clotting enzyme (Stenoxobin), from the venom of Lachesis muta stenophyrs, was
      purified by gel chromatography on Bio-gel P-100 followed by agmatine CH-Sepharose
      4B and FPLC on Mono Q column. By SDS polyacrylamide gel electrophoresis the mol.
      wt was found to be 37,000. The enzyme is a glycoprotein with 1.6 moles of sialic
      acid per mole of protein and has an average content of 7.0% of neutral
      carbohydrates. The clotting and esterolytic (BAEE) activities were 843 NIH
      units/mg and 60.1 +/- 1.2 OD225 ml/min/mg, respectively, and could not be
      inhibited by heparin or hirudin. Amino acid analysis revealed a low content of
      tryptophan and a high content of acid residues. Stenoxobin acts upon human
      fibrinogen by releasing consecutively fibrinopeptides A and B from the alpha- and
      beta-chains of fibrinogen.

PMID- 8310445
TI  - Coagulation factor X inhibitor from hundred-pace snake (Deinagkistrodon acutus)
      venom.
AB  - Deinagkistrodon acutus venom contains a collection of anticoagulant proteins that
      has been reported to prevent prothrombinase assembly (Teng and Seegers, 1981,
      Thromb. Res. 23, 255). A partial sequence indicates that these proteins are
      related to the functionally equivalent protein in Trimeresurus flavoviridis
      (Atoda et al., 1991, J. Biochem. 106, 808). Inhibition of prothrombinase, the
      complex of Factors Xa and Va combined with phospholipids, is expressed in bovine,
      human, and rat plasmas as indicated by an assay dependent on only prothrombinase
      activity. The concentration dependence of inhibition of prothrombin conversion by
      different combinations of the components of bovine prothrombinase under the same
      conditions yielded estimates of apparent dissociation constants of 104 nM and 2
      nM for complexes of the inhibitor with Factor Xa and with Factors Xa and Va,
      respectively. Because this inhibitor does not prevent Factor Xa alone from
      converting prothrombin, but blocks the other combinations, we conclude the
      inhibitor prevents the complex of Factors Xa and Va from binding to phospholipid
      surfaces and to prothrombin. The inhibitor also blocks the activation of Factor X
      by Factor VIIa and thromboplastin as well. However, the inhibitor has no effect
      on thrombin-induced clotting or fibrinolysis induced by either plasminogen
      activator or streptokinase. Therefore, this inhibitor has several properties
      required of an anticoagulant, therapeutic agent.

PMID- 8310446
TI  - [Characterization of the biological activities of the 'yellow' and 'white' venoms
      from Crotalus durissus ruruima compared with the Crotalus durissus terrificus
      venom. Neutralizing activity of Crotalus durissus ruruima antivenins].
AB  - The biological activities of 'yellow' and 'white' venom of a rattlesnake Crotalus
      durissus ruruima Hoge, 1965, found in the savanna-like vegetation (cerrado) of
      northern Brazil (Roraima) and Venezuela have been studied, and compared to the
      reference Crotalus durissus terrificus venom. The lethal activity of venoms
      depended on the inoculation route. The most toxic venom was the white one. The
      venoms of C. d. terrificus and the yellow of C. d. ruruima had similar
      lethalities. The yellow venom of C. d. ruruima showed a caseinolytic activity
      three times higher than that obtained with either the venom of C. d. terrificus
      or the white one of the C. d. ruruima. Hemorrhagic and necrotic activities were
      found only in the yellow venom. White and yellow venoms from C. d. ruruima showed
      a similar action on fibrinogen; this thrombin-like action was greater with C. d.
      terrificus venom. On histopathological sections local and pulmonary hemorrhage
      was found only with the yellow venom, but myonecrotic activity was observed with
      both venoms of C. d. ruruima. Among all antivenoms studied, the anti-bothropic
      crotalic was the best at neutralizing hemorrhagic and hemolytic activities. These
      results suggest that antivenom bothropic-crotalic should be used in the treatment
      of patients with snakebite by C. d. ruruima: besides its neutralization on lethal
      activity, it also neutralizes the hemorrhagic activity present in some venoms.

PMID- 8310447
TI  - Stonustoxin: a highly potent endothelium-dependent vasorelaxant in the rat.
AB  - Stonefish venom has been documented to cause marked hypotension and respiratory
      difficulties in envenomed animals. Stonustoxin, a lethal protein recently
      isolated from the venom of the stonefish Synanceja horrida produced hypotension
      and, at concentrations above 20 micrograms/kg, death in anaesthetized rats, with
      no observable effects on nerve-evoked twitches of the tibialis and diaphragm
      muscles. Stonustoxin (20-160 ng/ml) induced endothelium-dependent relaxations of
      rat thoracic aortae precontracted with noradrenaline. Higher concentrations
      induced relaxations followed by contractions. Methylene blue, haemoglobin and the
      specific NO-synthase inhibitor L-NG-nitro arginine methyl ester inhibited
      stonustoxin-induced relaxations, while the cyclooxygenase inhibitor indomethacin
      was without effect. The results of the present study show that stonustoxin causes
      marked vasorelaxation of the rat isolated aorta, which appears to be due to the
      release of endothelium-derived relaxing factor (probably nitric oxide or nitric
      oxide-yielding substances) from the vascular endothelium, and this may be
      responsible for the in vivo hypotensive and lethal actions of stonustoxin and of
      stonefish venom.

PMID- 8310448
TI  - Hydrolytic specificity of three basic proteinases isolated from the venom of
      Bothrops moojeni for the B-chain of oxidized insulin.
AB  - The hydrolytic activity of three basic proteinases isolated from Bothrops moojeni
      venom was determined on the B-chain of oxidized insulin. The serine proteinases
      MSP1 and MSP2 cleave the insulin B-chain at identical positions and in the same
      order of bond cleavage. Cleavage occurs first at the Arg-Gly(22-23) position,
      followed by hydrolysis of the Lys-Ala(29-30) peptide bond. The metalloproteinase
      MPB differs from the serine proteinases in cleaving the insulin B-chain very
      rapidly at four positions: Ser-His(9-10), Ala-Leu(14-15), Tyr-Leu(16-17) and Phe
      Phe(24-25).

PMID- 8310449
TI  - Distribution and elimination of ingested brevetoxin (PbTx-3) in rats.
AB  - As a first step towards understanding the pathologic effects of ingested
      brevetoxin (PbTx) in marine mammals, we determined how [3H]PbTx-3 was distributed
      and eliminated when ingested at sub-lethal dosages (18.6 micrograms/kg) by
      Fischer 344 rats. Brevetoxin was distributed widely in the body, but concentrated
      primarily in the liver. It was eliminated in equivalent quantities through the
      urine and feces. However, we believe urinary clearance is the primary route for
      PbTx-3 absorbed from the gastrointestinal tract.

PMID- 8310450
TI  - The Ah receptor: mediator of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) and related compounds.
AB  - A considerable body of research over the past fifteen years establishes that in
      laboratory animals the Ah (aromatic hydrocarbon) receptor (AhR) mediates most, if
      not all, toxic effects of halogenated aromatic hydrocarbons such as
      polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and
      polyhalogenated biphenyls. More recently the AhR has been shown to also exist in
      a wide variety of human tissues and human cell lines. In general the AhR in
      humans appears to function very much like the AhR in rodents. However, the
      affinity with which toxic HAHs such as 2,3,7,8-tetrachlorodibenzo-p-dioxin bind
      to the AhR from human sources generally is lower than the affinity with which
      these HAHs bind to the Ah receptors from rodent tissues. This lower affinity may
      explain, in part, why the human species seems less sensitive than many laboratory
      animals to the effects of HAHs. The AhR enhances transcription of genes encoding
      cytochrome P450 enzymes in the CYP1A subfamily, but most of the toxic effects of
      HAHs do not seem to require P450 induction per se. Recent molecular approaches to
      the mechanism of HAH toxicity indicate that the AhR also may mediate expression
      of several other genes, including genes that regulate cell growth and
      differentiation. Despite the expanding repertoire of cellular responses known to
      be altered by HAHs (potentially through the AhR) it is not yet clear which AhR
      mediated actions are the key events in HAH toxicity. Within the past year two
      subunits of the AhR have been cloned; this cloning, along with other molecular
      investigations, should greatly expand our opportunity to understand the specific
      mechanisms and pathways by which HAHs cause toxicity.

PMID- 8310451
TI  - Attenuation of acetaminophen hepatotoxicity in mice as evidence for the
      bioavailability of the cysteine in D-glucose-L-cysteine in vivo.
AB  - A substantial fraction of the cysteine added to total parenteral nutrition (TPN)
      solutions is converted to the corresponding thiazolidine derivative, while in
      solution with relatively large concentrations of glucose typical of TPN (700 mM
      and higher). It was recently reported (Roberts et al. (1987) J. Med. Chem. 30,
      1891-1896) that this thiazolidine, D-glucose-L-cysteine (DGC), offered no
      significant protection against the hepatic injury caused by 5 mmol/kg of
      acetaminophen in mice, suggesting that the cysteine present as DGC is poorly
      bioavailable in vivo. In the present study, fasted male ICR mice given 1.6 or 2.6
      mmol/kg of acetaminophen sustained hepatic injury, estimated by elevations in
      plasma alanine aminotransferase (ALT) activities. Administration of 2.5 mmol/kg
      of N-acetylcysteine (NAC) 1 h before acetaminophen given i.p. prevented the rise
      in plasma ALT activities, apparently through support of glutathione (GSH)
      synthesis. Administration of 2.5 mmol/kg of DGC prior to acetaminophen resulted
      in slightly lower mean plasma ALT activities than were observed in animals given
      saline before acetaminophen, but the effect was not statistically significant.
      When DGC was given 1 h before p.o. administration of 1.6 or 2.6 mmol/kg of
      acetaminophen, the protective effects of DGC were statistically significant (P <
      0.01, 0.025, respectively), although NAC afforded significantly greater
      protection than did DGC at the higher dose of acetaminophen. Given 4 h before
      acetaminophen, DGC attenuated acetaminophen-induced increases in plasma ALT
      activities significantly, whereas NAC was without effect. These results indicate
      that the cysteine in DGC is at least partially bioavailable in vivo and, further,
      that DGC may function as a slow release formulation of cysteine.

PMID- 8310452
TI  - Toxic interactions between copper sulphate and some organic agrochemicals.
AB  - Groups of rats were treated with graded doses of zineb or aldicarb solely or in
      association with copper sulphate for nine consecutive weeks. Body weight gain was
      retarded and thymus gland weight was decreased in all treated groups. A
      pronounced synergism between copper sulphate and zineb was noticed in lowering
      the weights of thymus, testes, and adrenal glands. Various degrees of reduction
      in hemoglobin concentration, red blood cells and platelet counts occurred after
      treatment with the above-mentioned agrochemical regimen. Copper sulphate
      synergised the elevation of serum alkaline phosphatase (AP) activity, and
      bilirubin concentration as well the reduction of hemoglobin concentration by
      zineb. Alanine aminotransferase (ALT) activity was significantly increased, while
      cholinesterase (ChE) activity was decreased in all treated groups. Serum
      triglycerides (TGs) were lowered in rats treated with medium or high doses of
      zineb or aldicarb.

PMID- 8310453
TI  - Toxic action of ethylene oxide on pulmonary cells (L132) cultured under aerobic
      conditions.
AB  - In environmental health, inhalation is the most prominent route of ethylene oxide
      (EO) exposure. In the current study, human embryonic pulmonary epithelial cells
      (L132 cell line) were exposed to EO following a prior adaptation to atmospheric
      conditions. A comparative study between two EO exposure conditions (0.07 and 0.18
      g/m3 gas injections) was carried out after a 1-h incubation. Whereas control
      cells were exposed to a pure air stream. The EO cytotoxicity was established by
      electron microscopy and LDH and ATP determinations after 1, 3, 6 and 24 h
      following the exposure. The ultrastructural examination revealed a remarkable
      vacuolisation of the exposed cells leading to cell death. In spite of this
      modification, the number of mitochondria and the content of endoplasmic reticulum
      increased in the L132 cells. For both exposure concentrations LDH was released
      into the extracellular milieu. In the presence of the high EO concentration, LDH
      activity increased with respect to the post-exposure time involving alteration of
      the membrane and permeability. For low EO exposure, ATP synthesis was
      significantly increased after 1 h of post-exposure (P < 0.01) and decreased to
      normal levels after 6 h. For the high EO concentration, however, ATP continually
      increased with respect to the post-exposure time. This indicates cellular
      stimulation and suggests the activation of a defense mechanism. This study shows
      a direct EO cytotoxicity on L132 cells cultured in atmospheric conditions.

PMID- 8310454
TI  - Dose-dependent study of liver lipid peroxidation related parameters in rats
      treated with pp'-DDT.
AB  - Rats treated with increasing doses of pp'-DDT (60, 100 and 180 mg/kg body wt.)
      i.p., for 24 h, showed a dose-independent increase in liver cytochrome P450
      levels, together with an increase in lipid peroxidation, measured as production
      of thiobarbituric acid reactants. This oxidant condition elicited in the liver by
      DDT was not accompanied by any change in the activity of NADPH-cytochrome c
      reductase or in the rate of superoxide anion generation by liver microsomal
      fraction. The activities of superoxide dismutase and glutathione peroxidase were
      found to be increased in the higher dose DDT-treated rats, without any change in
      those from catalase and glutathione reductase. The results presented showed an
      oxidant condition in the liver elicited by DDT treatment of rats, without any
      adequate hypothesis proposed to explain these data.

PMID- 8310455
TI  - Cadmium-induced hepatotoxicity in three different rat strains.
AB  - Cadmium (Cd) is a highly toxic element able to induce acute liver injury in rats
      after intraperitoneal administration. The dose-dependent Cd-induced
      hepatotoxicity was examined in three different rat strains. A difference in
      hepatotoxicity was observed in the three rat strains, determined by the
      examination of serum enzymes' activities and other biochemical parameters, all
      markedly altered after Cd intoxication. The histological findings came to confirm
      the variations of the above-mentioned parameters. It is concluded that the
      administration of this toxic agent caused different toxicity in the three rat
      strains examined, indicating a more intense damage in Wistar than in Quinster and
      Lewis rats.

PMID- 8310456
TI  - The regional hydrolysis of ethyl acrylate to acrylic acid in the rat nasal
      cavity.
AB  - Cytotoxicity is primarily limited to the olfactory epithelium of the dorsal
      meatus region of the nasal cavity of rodents following inhalation exposure to
      acrylic monomers. To investigate the biochemical basis for this effect, three
      regions of the Fischer F344N rat nasal cavity were evaluated for carboxylesterase
      activity for the representative acrylic ester, ethyl acrylate. Prior studies have
      indicated that the rodent olfactory epithelium is sensitive to the cytotoxic
      effects of short chain organic acids. In this study, no regional difference in
      carboxylesterase activity was observed between sensitive and non-sensitive
      regions of olfactory epithelium. Respiratory epithelium (resistant to
      cytotoxicity) was found to be have a much lower rate of carboxylesterase activity
      than olfactory epithelium. These results suggest that the regional distribution
      of cytotoxicity observed in the rat nasal cavity at high concentrations of
      inhaled acrylic monomers may be due in part to the amount of released organic
      acid following deposition. However, the observation of the same esterase activity
      in sensitive and nonsensitive olfactory regions suggests that nasal air flow
      patterns and regional deposition may also be critical factors.

PMID- 8310457
TI  - In vitro esterification of fatty acids by various alcohols in rats and rabbits.
AB  - The ability of six alcohols--1-propanol, 2-propanol, 1-butanol, 1-amyl alcohol,
      isoamyl alcohol and 1-octanol--to esterify fatty acids in vitro was determined in
      liver, lung and pancreas from rats and rabbits by incubating tissue homogenates
      with [14C]oleic acid and isolating and quantifying the esterified fatty acid.
      There was considerable variation in the amount of esterified fatty acid formed
      depending upon the alcohol. The relative rates of formation among the tissues
      were pancreas >> liver > lung. In view of the deleterious effects associated with
      the esters formed by ethanol, consideration must also be given to these other
      alcohols as well.

PMID- 8310458
TI  - Genotoxicity of tritiated water in human lymphocytes.
AB  - The present study was carried out to evaluate the genotoxicity of tritium,
      administered as tritiated water, in peripheral blood human lymphocyte cultures.
      Sister-chromatid exchanges (SCE) and chromosome aberrations (CA) were scored as
      genetic endpoints. From our results we can conclude that beta-radiation from low
      concentrations of tritium was able to induce a significant increase in the
      frequency of CA, although it was ineffective in increasing the frequency of SCE.

PMID- 8310459
TI  - The toxicity of organophosphate compounds towards cultured PC12 cells.
AB  - The effects of three representative organophosphates (OPs), tricresyl phosphate
      (TCP), triphenyl phosphite (TPP) and paraoxon (POX) on the proliferation and
      viability of rat PC12 pheochromocytoma cells were studied. With respect to its
      IC50, TCP was at least an order of magnitude more potent in its antiproliferative
      activity than both TPP and POX. All test OPs were cytotoxic at concentrations
      inhibiting cell proliferation. No compound inhibited cell growth below 10
      micrograms/ml. For TCP and TPP the estimated IC50 values from proliferation
      assays were lower than published LD50 values in vivo, whereas paraoxon was much
      less toxic in vitro than in vivo. Subcytotoxic levels of TCP (1 micrograms/ml)
      were found to inhibit the maintenance of neurites on cells grown in the presence
      of nerve growth factor.

PMID- 8310460
TI  - A 12-month study of policosanol oral toxicity in Sprague Dawley rats.
AB  - Policosanol is a natural mixture of higher aliphatic primary alcohols. Oral
      toxicity of policosanol was evaluated in a 12-month study in which doses from 0.5
      to 500 mg/kg were given orally to Sprague Dawley (SD) rats (20/sex/group) daily.
      There was no treatment-related toxicity. Thus, effects on body weight gain, food
      consumption, clinical observations, blood biochemistry, hematology, organ weight
      ratios and histopathological findings were similar in control and treated groups.
      This study supports the wide safety margin of policosanol when administered
      chronically.

PMID- 8310461
TI  - Regioselective metabolism of benzo[a]pyrene and 7-chlorobenz[a]anthracene by fish
      liver microsomes.
AB  - Many polycyclic aromatic hydrocarbons (PAHs) and chlorinated PAHs in the
      environment are potent mutagens and carcinogens. Using benzo[a]pyrene (BaP) and 7
      chlorobenz[a]anthracene (7-Cl-BA) as representatives of PAHs and chlorinated
      PAHs, respectively, we studied the metabolism of these compounds in liver
      microsomes of Tilapia (Oreochromis hybrid), one of the most common fish in south
      Asia. The regioselective metabolism of BaP and 7-Cl-BA by the fish liver
      microsomes resulted in the formation of hydroxylated and trans-dihydrodiol
      metabolites of both BaP and 7-Cl-BA. The metabolites were purified by HPLC and
      identified by both UV/VIS and mass spectroscopic methods. The fish liver
      microsomes metabolized BaP to form BaP-7,8-dihydrodiol (11%), 3-hydroxy-BaP
      (17%), and 9-hydroxy-BaP (22%) as the major products and metabolized 7-Cl-BA to
      form 7-Cl-BA trans-8,9-dihydrodiol as the major metabolite (40%). The Tilapia
      liver microsomal P-450 enzyme activities were inducible by pretreatment with 3
      methylcholanthrene (3-MC), which increased microsomal aryl hydrocarbon
      hydroxylase and 7-ethoxyresorufin O-deethylase activities by 74- and 360-fold,
      respectively. The induction of these enzymes by 3-MC was greater in fish
      microsomes than in rat liver. This study is the first to demonstrate the
      regioselective metabolism of BaP and 7-Cl-BA by fish liver microsomes.

PMID- 8310462
TI  - A career plundered.
AB  - Dr. Margaret Bean-Bayog, a Boston psychiatrist, was sued by the Lozano family
      after a former patient, Paul Lozano, committed suicide. The case was widely and
      sensationally publicized in the newspapers and other media. A combination of
      inaccurate reporting, inept proceedings by the Massachusetts Board of
      Registration in Medicine, and the threat of ruinous legal fees led Dr. Bean-Bayog
      to surrender her license to practice medicine. Facts that were not reported in
      the press were described in Dr. Maltsberger's address, delivered on April 15,
      1992, at the annual AAS meeting in San Francisco. The implications for therapists
      attempting to treat seriously suicidal patients in the current hostile forensic
      climate were further discussed. The text of the address is presented here.

PMID- 8310463
TI  - Some controversies in suicidology: toward a mentalistic discipline.
AB  - The main assertion in this paper is that psychache (mental pain) has a life of
      its own and is separate from the study of the brain, the organ that cradles the
      processes of the mind. No amount of biologicizing or medicalizing suicide can
      gainsay the fact that the human impulse of self-destruction is a decision of mind
      to put an end to the flow of its own unbearable conscious contents, to stop the
      psychache. The explanations for suicidal actions lie in the Oxford English
      Dictionary, not in the Diagnostic and Statistical Manual of Mental Disorders.
      Unless suicidology asserts and maintains the position that suicide is essentially
      psychachical, that the main focus of suicidal action is in the mind (as opposed
      to the mind's somatic abode, the brain), it will lose its identity and its
      usefulness. This is not just a quarrel over professional territory, money, or
      power; it is a philosophic war, a fight for the very soul of suicidology--and of
      the mind.

PMID- 8310464
TI  - Consultation and the suicidal patient.
AB  - This paper presents an argument for a paradigm shift in the way that mental
      health professionals approach their work with psychiatric patients in the midst
      of a suicidal crisis and suggests that the time has come to discuss a standard of
      care based on integration of detected risk factors, effective education and
      training in suicidology, and most importantly, the routine use of consultation
      and teamwork. Also proposed is a workable model for the use of consultation that
      has a number of major components: quality education in suicidology, the training
      and availability of appropriate consultants, clinical teamwork, and the
      recognition by training programs and clinical institutions that it is necessary
      to routinely consider a consultative risk management approach for work with
      suicidal patients.

PMID- 8310465
TI  - Adequacy of official suicide statistics for scientific research and public
      policy.
AB  - Many researchers have claimed that the study of suicide and the formation of
      public policy are not undermined by the misclassification of suicide as other
      causes of death. We evaluated this claim using a new technique and causes of
      death not previously considered. We examined computerized California death
      certificates, 1966-1990. Mortality peaks at symbolic ages are a characteristic
      feature of suicide. We sought such peaks in (1) causes of death commonly
      suspected of containing misclassified suicides (e.g., accidental barbiturate
      poisoning), (2) causes of death not hitherto suspected (e.g., pedestrian deaths),
      and (3) control groups. The first two categories displayed peaks at symbolic
      ages, but control groups did not. The size of the peak, indicative of
      misclassified suicides, varied markedly by race (p < .0001) and sex (p < .0001).
      Misclassification is evident for all time periods examined, large and small
      counties, and each race and sex. The maximum misclassification occurs for Blacks
      (14.92% of officially recorded suicides). We conclude that suicides are
      misallocated to at least five other causes of death (two of which have not been
      previously considered in the literature) and are most likely to be underreported
      for groups with low official suicide rates, that is, Blacks and females.
      Consequently, Blacks and females are not as protected from suicide as was
      previously supposed. It may be inadvisable to use official suicide data to test
      scientific hypotheses about suicide, unless the effects of underreporting are
      estimated and, if necessary, corrected for.

PMID- 8310466
TI  - Long-term outpatient treatment in alcoholics with previous suicidal behavior.
AB  - The importance of previous suicidal behavior for the treatment of alcoholics was
      analyzed in a long-term outpatient treatment study. In a series of 72 patients,
      21 patients, (29%), 17 men and 4 women, had previously made at least one suicide
      attempt or had seriously threatened to kill themselves (3 cases). In comparison
      with the other alcoholics, those with previous suicidal behavior had a similar
      attrition rate, they were not more troublesome in treatment, and they had the
      same rate of favorable outcome during the third year after start of treatment.
      They differed from the other alcoholics in having a more severe abuse and a less
      favorable outcome during the initial part of the treatment. In conclusion, our
      results support the possibility of a long-term outpatient treatment strategy in
      alcoholics with previous suicide attempts.

PMID- 8310467
TI  - Campus student suicide rates: fact or artifact?
AB  - A review of all English-language studies (14 foreign and 17 American) on campus
      student suicides was undertaken. Only studies reporting original data and
      containing sufficient demographic information to compute standard mortality rates
      (SMR) or crude suicide rates were analyzed and organized into single-site
      studies. Only 4 single-site studies had a higher suicide rate than the comparable
      populations. Multiple-site collaborative studies done in the United States since
      1960 strongly suggest a campus student suicide rate significantly less than in
      the matched control population. However, deficiencies in case finding, case
      definition, sampling bias, and statistical techniques may place these conclusions
      in doubt. The author outlines research methods that might be applied to future
      multiple-site studies to resolve questions related to late adolescent and young
      adult suicidal behavior on campus and in other similar educational settings.

PMID- 8310468
TI  - Life events and social support in suicide.
AB  - In a conceptual framework of suicide process, literature on life events and
      social support in suicide is reviewed. Few studies have centered on these issues,
      and the existing research has many methodological ambiguities. However, it can be
      concluded that life events play an important role in suicide process as risk and
      precipitating factors. The findings on disintegration of social networks and poor
      social support indicate lack of protective factors. Implications for future
      research are discussed. Further research focusing on more specific questions on
      the role of life events and social support as well as their interactions is
      needed.

PMID- 8310469
TI  - Adolescent development and youth suicide.
AB  - The adolescent years, being a period of unique developmental changes, are of
      great interest in understanding suicidal behavior. The occurrence of completed
      suicide by age in 1-year age groups in adolescence and young adulthood was
      studied via official Finnish mortality statistics and the population statistics.
      Suicide rates increased sharply by age during adolescence, starting somewhat
      earlier among boys than among girls. During the periods of rapidly rising and
      high suicide rates in the 1970s and 1980s among boys, the increase in suicide
      rates started at a younger age than during a spell of lower rates in the 1960s.

PMID- 8310470
TI  - Suicidality among adolescent Alberta Indians.
AB  - A high rate of suicide attempts and suicide ideation characterized a sample of
      229 grade 7 to 9 adolescents resident on seven reserves in central Alberta. The
      prevalence of suicidality for these adolescent Indians was very similar to rates
      reported for Navajo youth and for 8th- and 10th-grade American non-Indian
      students. Comparison of Indian and non-Indian suicidality risk factors showed
      somewhat elevated levels of family disruption and psychological problems among
      Indian adolescents. Compared to Canadian nonadolescents, substance abuse levels
      were high, and conditions necessary to modeling were virtually omnipresent.
      Suicide ideation was significantly elevated for Indian adolescents with low
      psychological well-being, no father in the home, and a prior suicide in the
      household. Controlling for age, risk factors for suicide attempts were heavy
      alcohol use, no father in the home, sleeping problems, and low psychological well
      being. The high rates of adolescent Native suicide imply that a much higher
      proportion of their suicide attempts succeed. Targeted, community-based
      counselling and educational programs are needed to address these problems.

PMID- 8310471
TI  - The case of Paul Framson.

PMID- 8310472
TI  - [6 pages of medical prescriptions in the Glagolitic Psalter 3/N of the Sinai
      Closter].
AB  - Between the pages 141 und 142 of the Sinai Glagolitic Psalter 3/N there are three
      sheets of smaller size, containing twenty-two medical prescriptions (Folio 141 a
      c). The order of prescriptions is different to the classifications of the famous
      ancient medical authors. Apart from general prescriptions, the text is also
      containing three prescriptions for women, children and horses' disease.
      Mediterranean plants, animal products, one sort of magic and minerals are listed
      as remedies. There is no exact information as to dose and way of preparing.
      Following linguistical characteristics, the text can be dated between beginning
      of the 12th and beginning of the 13th century. Contents are a philological
      analysis of the text, and a comparison of ancient medical and botanical texts.

PMID- 8310473
TI  - [Physician satire and patient scorn in Hans Sachs' old Nurnberg and the
      physicians].
AB  - Among the best poems of Hans Sachs quite a few describe patient-physician
      relationships in 16th century Nuremberg. These poems offer a vivid impression of
      the technical aspects as well as of the social context of medical treatment at
      the time. Hans Sachs ridiculed the doctors and their patients, implying that
      everybody attempted to cheat the other side, and he provides evidence of a great
      influence of charlatans on the country population. The poems of Hans Sachs are
      extraordinary pieces or art; their aesthetics, though, appear unusual to us
      today. Medical satire is part of all European cultures, and has been written
      throughout medical history. Most motives of later satires focussing on physicians
      may be traced to Hans Sachs' poetry.

PMID- 8310474
TI  - [The surgeon from the Weser (circa 1200-1265)--a fortunate find in archaeology
      and medical history].

PMID- 8310475
TI  - [Early Western observations of moxibustion and acupuncture].
AB  - Earlier research has maintained that the earliest passage of written information
      about acupuncture and moxibustion to Western Europe took place around the middle
      of the 17th century. But an investigation into the letters, 'historias',
      dictionaries, grammars, etc. of the Jesuit mission in Japan, which started in
      1549, shows that the missionaries there already enjoyed a considerable knowledge
      of both methods of treatment. These sources also reveal indications of the use of
      needles and moxa on horses as well as the use of 'hammer-needles', a Japanese
      invention which was later described in detail by Willem ten Rhijne and Engelbert
      Kaempfer. Furthermore some central Sinojapanese terms of anatomy, physiology and
      pulse diagnosis in the light of their European interpretations, and a hitherto
      unknown outline of Japanese medicine found in an early French book on Chinese
      sphygmology are presented.

PMID- 8310476
TI  - [2 images of the orthopedist Johann Georg Heine (1771-1838)].

PMID- 8310477
TI  - [Promotion of Otto Heubner, founder of the Leipzig Pediatric Clinic (when and how
      was O. Heubner promoted)?].

PMID- 8310478
TI  - Electronic verification of donor-recipient compatibility: the computer
      crossmatch.
AB  - BACKGROUND: This article describes standard operating procedures (SOPs) for a
      computer crossmatch to replace the immediate-spin crossmatch for ABO
      incompatibility between patient blood samples submitted for pretransfusion
      testing and the blood component selected for transfusion. These SOPs were
      developed following recent changes to the Standards for Blood Banks and
      Transfusion Services of the American Association of Blood Banks (AABB). STUDY
      DESIGN AND METHODS: SOPs were developed, utilizing currently available software,
      for pretransfusion testing. The SOP for donor unit processing entails bar code
      entry of the unit number, component name, and ABO/Rh type; computer entry and
      interpretation of serologic reactions; warning of discrepancies between bar code
      entered blood type and result interpretation; and quarantine of the donor unit in
      such instances. The SOP for patient sample testing requires bar code entry of
      specimen accession number, which accesses patient demographics; computer entry
      and interpretation of ABO/Rh tests; repeat blood typing at the time of crossmatch
      if only one patient blood type is on record; and warning if there are
      nonconcordant current and historical blood types. The computer crossmatch SOP
      requires bar code entry of specimen accession and donor unit numbers; release of
      group O red cells pending resolution of discrepancies; and immediate-spin
      crossmatch during computer downtime. Tables validated on-site prompt warning
      messages and prevent both computer crossmatch and release if blood components of
      the wrong ABO type are selected. RESULTS: These SOPs meet the requirements of the
      15th edition of the AABB Standards. Projected annual time savings at this
      institution are > 100,000 workload recording units. Further benefits include
      reduced patient sample volume requirements, less handling of biohazardous
      material, and elimination of unwanted positive or negative reactions associated
      with the immediate-spin crossmatch. Release of incompatible blood components when
      the wrong patient blood type is on record is addressed by requiring the use of
      group O red cells in the absence of two concordant blood types, one of which must
      be from a current sample. CONCLUSION: A combination of existing computer programs
      and carefully developed SOPs can provide a safe and efficient means of detecting
      donor-recipient incompatibility without performance of serologic crossmatch.

PMID- 8310479
TI  - The necessary and the unnecessary transfusion: a critical review of reported
      appropriateness rates and criteria for red cell transfusions.
AB  - BACKGROUND: The purpose of this study was to evaluate the criteria for assessing
      the appropriateness of red cell transfusions. The data were obtained by a
      computer search of all English-language literature from 1966 to October 1992.
      STUDY DESIGN AND METHODS: Nine studies were selected, which dated from 1986 to
      1989 and employed explicit criteria evaluating the appropriateness of red cell
      transfusion in adults. The following data were abstracted from all studies: study
      design, timing, location, criteria for evaluating appropriateness, and rate of
      appropriate or inappropriate transfusions. RESULTS: Five studies evaluated
      transfusion appropriateness. Appropriateness rates ranged from 88 to 99 percent
      in three studies, and inappropriateness rates ranged from 0.3 to 57.3 percent in
      two studies. Four studies evaluated transfusion inappropriateness and reported
      inappropriateness rates of 18 to 55 percent. Substantial variation was found in
      the criteria for an appropriate or an inappropriate transfusion. Appropriateness
      rates did not depend upon characteristics of the study design, location, or
      timing of data collection. Restrictiveness in the criteria used to determine
      appropriateness and the use of additional implicit evaluation after an initial
      explicit review affected appropriateness rates. CONCLUSION: In the 1980s, high
      rates of inappropriate transfusion and low rates of appropriate transfusion were
      still reported. Appropriateness rates varied widely, in part because of marked
      variation in the criteria for an appropriate transfusion. Newly derived standards
      for an appropriate red cell transfusion, published in 1992, appear to provide a
      simple and objective means of evaluating the appropriateness of a transfusion.
      Appropriateness rates resulting from the application of these new standards have
      not yet been determined.

PMID- 8310480
TI  - Concurrent comparison of the safety of paid cytapheresis and volunteer whole
      blood donors.
AB  - BACKGROUND: Historically, paid blood donors were found to transmit hepatitis at
      higher rates than volunteers. In those older studies, paid donors frequently were
      recruited from prisons or slum areas--a finding consistent with the belief that
      monetary payment in itself did not necessarily lead to the high-risk status of
      commercial blood. Instead, it was the population base from which the donors were
      recruited that was important. STUDY DESIGN AND METHODS: Today, cytapheresis
      donors are in great demand. Because payment is one incentive that might entice
      donors to undertake the increased commitment of repeated cytapheresis donation,
      the results were studied of infectious disease history and laboratory testing
      performed concurrently in 917 volunteer whole-blood donors and 1240 paid
      cytapheresis donors, who were enrolled in distinct programs at the DeGowin Blood
      Center from October 7, 1987, through November 30, 1990. RESULTS: When first,
      repeat, and overall donations made by these donors were evaluated separately,
      paid cytapheresis donors were found to exhibit no increase in infectious disease
      history or test results beyond those of volunteer whole-blood donors. CONCLUSION:
      Thus, paid cytapheresis donors, when managed within a formal program, should not
      necessarily be presumed to be more dangerous than volunteers, from an infectious
      disease aspect. However, definitive proof of safety (comparison of transfusion
      transmitted infection rates in two groups of patients receiving blood components
      exclusively from either paid cytapheresis or volunteer donors) was not pursued by
      long-term follow-up studies.

PMID- 8310481
TI  - Long-term follow-up testing of red cell alloantibodies.
AB  - BACKGROUND: In previous studies, 29 to 34 percent of potentially hemolytic red
      cell antibodies were not detected after short-term follow-up. STUDY DESIGN AND
      METHODS: To examine long-term detection, records were reviewed for 44 consecutive
      patients who were tested more than 5 years after their potentially hemolytic red
      cell antibodies were first identified in this hospital. RESULTS: After 5 to 10
      years, 14 (39%) of 36 Rh, Kell, and Duffy system antibodies were not detected on
      at least one occasion. Twenty-two other such antibodies were sought again after
      more than 10 years; 10 (45%) were not detected. When restimulation by pregnancy
      was excluded, these rates were 42 and 48 percent, respectively. CONCLUSION:
      Clinically significant red cell antibody formation is probably more common than
      previously realized, because nearly half of these antibodies are undetected after
      long-term follow-up.

PMID- 8310482
TI  - Evaluation of indeterminate c22-3 reactivity in volunteer blood donors.
AB  - BACKGROUND: Approximately 25 percent of blood donor sera that are repeatably
      reactive for hepatitis C virus (HCV) on second-generation enzyme immunoassay (EIA
      2.0) are indeterminate on second-generation recombinant immunoblot assay (RIBA
      2.0), and over 76 percent of these results are due to single reactivity to the
      HCV recombinant antigen c22-3. STUDY DESIGN AND METHODS: Data are presented on 46
      volunteer allogeneic blood donors who were reactive on EIA2.0 and c22-3
      indeterminate in RIBA 2.0. Index and follow-up samples were evaluated by using a
      panel of five synthetic peptide EIAs, a prototype strip immunoblot assay that
      uses synthetic peptides in addition to recombinant protein (RIBA 3.0), and
      polymerase chain reaction (PCR) for HCV RNA. RESULTS: All 46 donations had normal
      alanine aminotransferase values; only 2 (4.3%) reacted for antibody to hepatitis
      B core antigen. With a panel of 12 synthetic peptides spanning the entire
      sequence of the c22-3 recombinant antigen, 33 plasmas (72%) reacted to one
      peptide or none, including 19 plasmas with reactivity restricted entirely to the
      N-terminal peptide (1-15 amino acids) of c22-3. With RIBA 3.0, 28 donations (61%)
      were nonreactive, including 25 that reacted with one peptide or none in EIA. Of
      these 25 plasmas, 18 reacted with the N-terminal sequence only. All 46 index
      donations were tested by PCR; the single PCR-positive unit reacted with four HCV
      peptides, was positive by RIBA 3.0, and reacted for antibody to hepatitis B core
      antigen. Twenty-six index donors were successfully recalled 3 to 7 months after
      their index donation. None seroconverted to positivity in RIBA 2.0, 1 was
      nonreactive, and 25 remained positive for c22-3 only. The restricted epitope
      reactivity in peptide EIA and RIBA 3.0 was maintained over time in all cases. All
      26 of the follow-up samples tested negative by PCR. CONCLUSION: On the basis of
      the restricted peptide reactivity and PCR negativity of index and follow-up
      samples, it is concluded that the majority of c22-3 RIBA 2.0-indeterminate
      results are due to nonspecific cross-reactivity to restricted (principally, N
      terminal) regions of HCV core antigen.

PMID- 8310483
TI  - Epidemiology of hepatitis C virus: a study of male blood donors in Saudi Arabia.
AB  - BACKGROUND: Few epidemiologic reports on the prevalence of hepatitis C in Saudi
      blood donors have been published. STUDY DESIGN AND METHODS: Men (of several
      nationalities) donating blood at the King Khalid National Guard Hospital (Jeddah,
      Saudi Arabia) were randomly selected (n = 744) for this study examining the
      prevalence of hepatitis C virus (HCV) in the local donor population, the
      relationship of antibody to HCV (anti-HCV) to the surrogate markers alanine
      aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc), and
      the effect of the use of these markers on the discard rate. RESULTS: The
      prevalence of anti-HCV in the group examined was 3.2 percent (24/744), with a
      significantly high prevalence of 24.5 percent (12/49) in donors who were Egyptian
      (p < 0.0001). Exclusion of this group would lower the prevalence to 1.7 percent
      (12/695). Anti-HCV prevalence peaked in the group aged 30 to 39, and a
      significant relationship was found between anti-HCV and ALT level > 65 U/L (p <
      0.0001). There was no significant relationship between anti-HCV and anti-HBc (p =
      0.66). The prevalence of anti-HCV in the Saudis studied was 1.7 percent (9/528).
      The prevalence of anti-HCV in non-Bedouin Saudis was significantly greater than
      that in Bedouin Saudis (7/165 [4.2%] vs. 2/363 [0.5%]; p < 0.01). The prevalence
      of anti-HBc was found to be 28.7 percent (214/744). The use of elevated ALT (> 90
      U/L) and anti-HBc as surrogate markers would increase the current discard rate
      (8.3%) by 2.8 and 23.8 percent, respectively. CONCLUSION: These findings
      demonstrate the practical difficulties of using anti-HBc as a surrogate marker
      for hepatitis C in areas endemic for hepatitis B virus.

PMID- 8310484
TI  - Prevalence and risk factors for hepatitis C antibodies in volunteer blood donors
      in Brazil.
AB  - BACKGROUND: Little is known about the prevalence, risk factors, and transmission
      of hepatitis C virus (HCV) in a nontransfused population, particularly in
      developing countries. STUDY DESIGN AND METHODS: To investigate the association
      between HCV seropositivity and some demographic variables, a case-control study
      was conducted on 138 seropositive donors among 4762 consecutive volunteer blood
      donors and 1101 seronegative controls in Rio de Janeiro, Brazil. Donors were
      initially screened by interview for male homosexuality, use of illicit drugs,
      tattoos, previous transfusions, venereal diseases, and jaundice. Eligible donors
      were then tested for HCV antibodies by enzyme-linked immunosorbent assay. A
      multivariate analysis was performed on age, ethnic group, gender, and prior
      donation. RESULTS: The overall prevalence of HCV seropositivity was 2.89 percent.
      An increased risk of seropositivity was demonstrated for nonwhite donors at an
      odds ratio of 2.11 (95% CI, 1.43-3.13), for males at 2.39 (95% CI, 1.01-5.7), and
      for prior donors at 1.66 (95% CI, 1.09-2.52). The risk of anti-HCV positivity
      increased markedly with age. Those at highest risk were the group 40 to 49 years
      old, with an odds ratio of 4.37 (95% CI, 2.39-7.99) versus the group 20 to 29
      years old. The group under 20 years old showed an odds ratio of 0.50 (95% CI,
      0.06-3.87) compared to the group 20 to 29 years old. These findings were equally
      significant in a univariate analysis. CONCLUSION: Our results suggest that HCV
      seropositivity is strongly associated with male sex, nonwhite ethnicity, and
      greater age. A significant number of seropositive donors were not detected by
      screening interview.

PMID- 8310485
TI  - Subcutaneous administration of recombinant human erythropoietin before cardiac
      surgery: a double-blind, multicenter trial in Japan.
AB  - BACKGROUND: Dose and injection times have not previously been determined for
      subcutaneously administered recombinant human erythropoietin that would allow
      sufficient deposition of blood for autologous use in cardiac surgery. STUDY
      DESIGN AND METHODS: A double-blind, multicenter trial of placebo (Group 1) and
      recombinant human erythropoietin at 12,000 IU (Group 2) and at 24,000 IU (Group
      3) was performed on 114 patients at 26 institutions to determine the dosage that
      would permit an 800-g preoperative deposit of blood for autologous use. The test
      drug was administered subcutaneously on Days 21, 14, and 7 prior to operation,
      and oral iron preparations at 200 mg per day were given for 21 days. There were
      28 patients in Group 1, 28 in Group 2, and 30 in Group 3, with 28 excluded for a
      violation of the protocol. RESULTS: Blood was safely drawn 14 and 7 days before
      operation from 22 patients in Group 1 (78.6%), from 26 in Group 2 (92.9%), and
      from all patients in Group 3 (p = 0.018). The hemoglobin level on the day before
      operation decreased by 1.1 +/- 1.1 g per dL (11 +/- 11 g/L) in Group 1 and by 0.9
      +/- 0.9 g per dL (9 +/- 9 g/L) in Group 2 and rose by 0.1 +/- 0.8 g per dL (1 +/-
      8 g/L) in Group 3, compared to initial levels. Allogeneic blood transfusion could
      be avoided in 62, 89, and 90 percent of Group 1, 2, and 3 patients, respectively
      (p = 0.013). CONCLUSION: The present study shows that subcutaneously administered
      recombinant human erythropoietin at a dose of 24,000 IU per week for 3 weeks is
      effective and sufficient to allow the safe deposition of 800 g of blood for
      autologous use in cardiac surgery.

PMID- 8310486
TI  - Declining efficacy of AIDS case list cross-referencing in human immunodeficiency
      virus look-back: 1981 through 1992.
AB  - BACKGROUND: The impact of AIDS case list cross-referencing in human
      immunodeficiency virus look-back was assessed. STUDY DESIGN AND METHODS: Post
      1977 blood donations from former donors identified by 11 collaborating health
      departments as having developed AIDS have been traced at Irwin Memorial Blood
      Centers since 1983. To assess the changing efficacy of AIDS case list cross
      referencing in identifying infected donors and recipients, trends in cases
      reported through December 1992 were analyzed. RESULTS: Previous donors (n = 638)
      were identified from 21,917 AIDS case listings, for an overall match rate of 2.9
      percent. The rate of detection of previous donors from listings of AIDS cases
      declined from a peak of 5.3 percent in 1985 to 1.6 percent in 1992. Overall, 86
      percent (1824/2122) of donations by persons later reported on AIDS case lists
      were made prior to January 1983 when risk exclusion measures were initiated. Of
      the 212 known infected recipients linked to AIDS case list donors, 87 (41%) were
      previously identified by other look-back approaches. The rate of identification
      of infected recipients detected exclusively through AIDS case listings declined
      from a mean of 21 per year from 1984 to 1987 to a mean of 3 per year from 1990 to
      1992. No transmissions have been documented from donations prior to 1979.
      CONCLUSION: These findings demonstrate the declining yield of AIDS case list
      cross-referencing as a trigger for human immunodeficiency virus look-back.
      Continued reevaluation of look-back programs is essential so that their various
      components may be curtailed when justified.

PMID- 8310487
TI  - Potential deferral criteria predictive of human immunodeficiency virus positivity
      among blood donors in Thailand.
AB  - BACKGROUND: To develop deferral criteria to prevent human immunodeficiency virus
      (HIV) transmission by recently infected blood donors in the seronegative "window"
      phase, routine data on donors at a university hospital were examined for factors
      predicting seropositivity. STUDY DESIGN AND METHODS: Records of all 281 HIV
      positive blood donors from August 1987 through September 1991 were
      retrospectively compared with those of 1076 randomly selected control donors
      matched only by year of donation. Four controls were selected for each HIV
      positive donor. RESULTS: The prevalence of HIV in 102,684 donor units during the
      period rose from 0.02 percent in 1987 to 0.52 percent in 1991. Multivariable
      analysis revealed that male sex (odds ratio [OR] = 26.4), VDRL test positivity
      (OR = 3.0), age 21 to 30 years (OR = 2.2; referent: 16-20-year-old group), and
      replacement donorship (OR = 1.4; referent: voluntary donors) were independent
      factors significantly associated with HIV positivity among these donors (p <
      0.05). Since replacement donorship cannot be avoided, only male sex, age 21 to 30
      years, and VDRL test positivity were considered as potential criteria. When these
      findings were extrapolated to all donors in 1990 and 1991, those with all three
      or only two (excluding VDRL test, because the results are known only after
      donation) of these high-risk factors had HIV positivity probabilities of 2.2 and
      1.0 percent, respectively. These probabilities were, respectively, 4.9 times (95%
      CI: 2.9 8.3) and 4.1 times (3.1, 5.4) the risk among other donors. However,
      applying such criteria would have eliminated 1.5 and 31.2 percent, respectively,
      of all HIV-negative donors in 1990 and 1991. The latter deferral proportion is
      too high to be acceptable. CONCLUSION: In Thailand, improved donor deferral
      criteria addressing sexual risk factors could lead to decreased probability of
      window-period donation, with an acceptable rate of deferral. Additional p24
      antigen testing may be indicated for donors at increased risk for HIV infection,
      specifically, men aged 21 to 30.

PMID- 8310488
TI  - Human T-lymphotropic virus type II in Panamanian Guaymi Indians.
AB  - BACKGROUND: Currently, human T-lymphotropic virus type II (HTLV-II) is the most
      prevalent human retrovirus, detected in persons presenting to donate blood in the
      United States. Only scant information is available with which to counsel HTLV-II
      seropositive deferred donors or other persons about the ways in which they may
      spread HTLV-II to others. STUDY DESIGN AND METHODS: To increase understanding of
      the modes of transmission of HTLV-II, a seroepidemiologic study was conducted
      among Panamanian Guaymi Indians, a recently identified focus of endemic HTLV-II
      infection. Subjects were tested for serologic evidence of infection by HTLV-II,
      HTLV type I, hepatitis B virus, and nine other infectious agents by enzyme
      immunoassays and specific confirmatory tests. RESULTS: Nine (8.3%) of 109 persons
      tested HTLV-II-seropositive. HTLV-II seropositivity was more likely in persons
      with serologic evidence of prior hepatitis B virus infection. Sexual contact with
      HTLV-II-seropositive partners, but neither parenteral exposure nor breast
      feeding, was identified as a risk factor for HTLV-II. CONCLUSION: In Guaymi
      Indians, HTLV-II appears to be spread primarily through sexual transmission.

PMID- 8310489
TI  - Phenotyping autologous red cells within 1 day after allogeneic blood transfusion
      by using immunomagnetic isolation of reticulocytes.
AB  - BACKGROUND: When a transfused patient develops multiple or weak blood group
      antibodies, posttransfusion phenotyping is useful in antibody identification. To
      perform a correct phenotyping after transfusion, isolation of autologous red
      cells is necessary. However, mature autologous red cells are impossible to
      separate from their donor counterparts. Since the proportion of autologous
      reticulocytes compared to donor reticulocytes increases rapidly after
      transfusion, selective isolation of reticulocytes provides autologous cells for
      antigen typing. STUDY DESIGN AND METHODS: Extensive phenotyping was performed on
      red cells from 10 surgical patients before transfusion and on red cells and
      reticulocytes after the transfusion of 5 or more red cell units. Reticulocytes
      were isolated by using an antibody against the human transferrin receptor coupled
      to magnetic beads. RESULTS: The data showed nearly full agreement between
      pretransfusion phenotyping of red cells and posttransfusion typing of
      reticulocytes. Correct phenotyping of transferred patients could be obtained 8 to
      10 hours after transfusion using isolated reticulocytes. CONCLUSION: This method
      is helpful in selecting compatible blood when patients have developed antibodies
      and have an urgent need for further transfusions.

PMID- 8310490
TI  - Incest diagnosis by comparison of alleles of mother and offspring at highly
      heterozygous loci.
AB  - BACKGROUND: Methods that detect a child's homozygosity by examination of allelic
      products are insensitive for diagnosing incest because, at a given locus, a
      homozygous state is expected with a frequency of only 0.25 when parents are first
      degree relatives. Furthermore, these methods are not specific if the population
      contains many homozygous individuals or silent alleles that cause apparent
      homozygosity. STUDY DESIGN AND METHODS: Use of highly heterozygous loci improves
      specificity, but not sensitivity. Sensitivity may be increased by observing for
      two kinds of mother-offspring similarities: an offspring of incest tends to be
      homozygous or heterozygous-identical with respect to its mother's phenotype. At
      each locus, two conditional probabilities may be calculated for a genetic
      observation, using allele frequencies expected under a state of incestuous mating
      versus mating within a specified population. The conditional probabilities at
      each locus are compared in a likelihood ratio to express a relative probability
      of incest. RESULTS: In a case of known sibling incest, three likelihood ratios
      were derived from variable number of tandem repeat phenotypes at five loci. When
      only offspring homozygosity was observed, the likelihood ratio was 75.3:1. When
      both homozygous- and heterozygous-identical phenotype similarities of offspring
      and mother were noted, the likelihood ratio was 130.4:1. When maternal obligatory
      alleles of the offspring were considered, the likelihood ratio was 262.4:1.
      CONCLUSION: Comparison of maternal and offspring phenotypes at highly
      heterozygous loci increases both sensitivity and specificity of genetic tests in
      cases of suspected incest.

PMID- 8310491
TI  - Mathematical and computer modeling of acute normovolemic hemodilution.
AB  - BACKGROUND: Advocates of acute normovolemic hemodilution (ANH) frequently neglect
      to consider the decreasing hematocrit of the patient during both hemodilution and
      the subsequent operative procedure and the need to begin transfusion at some
      minimal hematocrit. STUDY DESIGN AND METHODS: For more accurate prediction of the
      efficacy of ANH, equations were derived and a computer model developed that
      allowed accounting for the decreasing hematocrit due to blood loss in an
      isovolemic patient and calculating the red cell volume on a minute-by-minute
      basis; the model also began the transfusion of ANH blood on a mL-for-mL basis
      when the minimal hematocrit was reached and transfused any remaining blood
      following completion of the case. The red cell volume saved by performing ANH for
      a given estimated blood volume (EBV) was expressed as either the fraction of the
      red cell volume of a routinely banked unit of blood (red cells stored in additive
      solution: volume 350 mL, hematocrit 0.65) or the number of units saved. RESULTS:
      The number of units saved in a typical example--EBV, 5000 mL; pre-ANH hematocrit,
      0.40; minimal hematocrit at which transfusion was begun, 0.25 over a range of
      estimated blood losses (500-2500 mL); and 1 to 5 ANH units drawn--never exceeded
      0.6. Even with extensive hemodilution, as in a child (EBV, 1500 mL; pre-ANH
      hematocrit, 0.40; minimal hematocrit at which transfusion was begun, 0.15; 5
      units drawn; and estimated blood losses, 2500, 1500, and 1000 mL) with a
      postdilution hematocrit of 0.16, the savings would have been only 0.29, 0.44, and
      0.49 units, respectively. CONCLUSION: Because of the decreasing hematocrit in a
      bleeding isovolemic patient and the need to begin transfusion at some minimal
      hematocrit, the theoretic savings in red cell volume attributable to ANH is less
      than had previously been appreciated, and additional ANH does not necessarily
      result in additional patient benefit.

PMID- 8310492
TI  - Rh-Hr: Alexander Wiener's last campaign.

PMID- 8310493
TI  - A partial E antigen in the Rh system?

PMID- 8310494
TI  - New immunoblot resolves indeterminate results for antibody to hepatitis C virus.

PMID- 8310495
TI  - Mean platelet volume as a platelet recovery predictor in platelet transfusion.

PMID- 8310496
TI  - Selection of white cell-reduced blood components for transfusions during early
      infancy.

PMID- 8310497
TI  - Contamination of fresh-frozen plasma with viable white cells and proliferable
      stem cells.

PMID- 8310498
TI  - Activation of transfused platelets in a patient with amegakaryocytic
      thrombocytopenic purpura.

PMID- 8310499
TI  - Requirements for the computer crossmatch.

PMID- 8310500
TI  - Donors and dollars.

PMID- 8310501
TI  - The persistence of blood group antibodies.

PMID- 8310503
TI  - Spontaneous acceptance of liver allografts in the rat. Analysis of the immune
      response.
AB  - In a model of arterialized rat liver transplantation, the biological indicators
      of liver dysfunction and the phenotype and in vitro function of graft
      infiltrating cells have been compared in rejected (DA-to-Lew) and spontaneously
      accepted (Lew-to-DA) grafts, 2-8 days after grafting. Recipients of rejected and
      nonrejected allografts had, during this time, similar loss in body weight and
      plasma levels of transaminase. The markers of cholestasis, however, increased
      from days 3 and 4 onward in the recipients of rejected grafts, but remained low
      and similar in the recipients of nonrejected allografts and those of syngeneic
      grafts. From days 2 to 6 the phenotype, IL-2 responsiveness, and donor-specific
      cytotoxic potential of the leukocytes infiltrating rejected and nonrejected
      allografts were comparable. On days 7 and 8, although the proportion of T cell
      subpopulations was identical in both combinations, activated CD4+ graft
      infiltrating cells were reduced in the nonrejected grafts. Also at this time,
      donor-specific cytotoxic cells were no longer detected in nonrejected grafts,
      whereas activity had reached a peak in the rejected grafts. These results suggest
      that liver grafts in both the LEW-->DA (grafts not rejected) and DA-->LEW (grafts
      rejected) strain combinations undergo tissue damage, but that the type of damage
      differs between the two combinations. Specifically, cholestasis was only observed
      in grafts that would subsequently be rejected. The difference in graft damage
      occurred at a very early time point (3 or 4 days after grafting), at which time
      neither the intensity nor phenotype of the graft infiltrate, its IL-2
      responsiveness, or its cytotoxic potential varied between the two combinations.
      Thus, a lack of immune reactivity, as assessed by these parameters, does appear
      not to be responsible for spontaneous acceptance of liver transplants in the LEW-
      >DA strain combination.

PMID- 8310502
TI  - Preservation of canine liver grafts using HTK solution.
AB  - HTK (histidine-tryptophane-ketoglutarate) organ preservation solution has been
      shown to be effective in human kidney transplantation, but the efficacy of HTK
      for extended liver preservation has not been determined. In this study, canine
      livers were preserved in HTK and compared with livers preserved in University of
      Wisconsin solution. First, the right and left liver lobes in dogs were flushed
      separately with cold HTK and UW, respectively, according to a double-flush
      method. After splitting the liver, the right and left lobes were stored at 4
      degrees C in either solution for 24 hr and 48 hr and assessed microscopically for
      parenchymal cell swelling, and enzyme histochemically for 5'-nucleotidase (5'-NT)
      as a marker of ischemic liver injury. Unlike livers preserved in UW (n = 5), HTK
      preserved livers (n = 5) showed progressive parenchymal cell swelling after 24-hr
      and 48-hr storage. The 5'-NT scores in HTK livers were lower than in UW livers,
      indicating increased storage injury (0-5% and 66-85% in HTK- and UW-preserved
      livers, respectively, after 48-hr storage). Second, graft function was tested in
      an orthotopic liver transplantation model in the dog. Whole livers were flushed
      in situ with cold HTK or UW and stored at 4 degrees C for 24 hr or 48 hr. Liver
      grafts stored in HTK were not washed out prior to reflow in the recipient, in
      contrast to grafts stored in UW. Livers preserved for 24 hr using HTK showed life
      supporting function after transplantation (n = 5, survival 12 hr-8 days). All
      grafts preserved for 48 hr in HTK did not function (n = 5, survival < 10 hr). UW
      preserved grafts all functioned after 24-hr storage (n = 5, survival > 6 days),
      as well as after 48-hr storage (n = 6, survival > 6 days). Peak serum glutamic
      oxaloacetic transaminase (SGOT) values after transplantation of 24-hr and 48-hr
      HTK-preserved livers did not differ from peak SGOT values of UW-preserved livers
      after similar preservation times. In conclusion, UW solution is more effective
      than HTK solution in extended preservation of canine liver grafts: 24-hr storage
      of livers preserved with HTK solution is feasible, whereas 48-hr storage results
      in a nonfunctioning graft.

PMID- 8310504
TI  - Prevention by liver transplantation of the graft-versus-host reaction and
      allograft rejection in a rat model of small bowel transplantation.
AB  - In the rat combination of DA (MHC haplotype RT1av1) donor into PVG(RT1c)
      recipient, liver grafts are not rejected and allow the acceptance of other organ
      grafts from the same donor strain. Here we show that an existing DA liver graft
      allows the acceptance of a DA small bowel graft in the PVG; the liver graft also
      prevented the graft-versus-host reaction normally associated with small bowel
      grafting. In addition, a liver graft could suppress the GVHR in F1 hybrid
      recipients of parental lymphoid cells, a classic GVHR model. GVHR suppression was
      immunologically specific and required that donor lymphocytes and liver be of the
      same strain. Besides their clinical implications, these results demonstrate the
      capacity of the liver for tolerance induction and suggest that it may play a
      physiological role in negative selection of T cells.

PMID- 8310505
TI  - Acceleration of chronic failure of intrahepatic canine islet autografts by a
      short course of prednisone.
AB  - A topic of current interest in islet transplantation is the selection of an
      optimal site for long-term graft survival since the intrahepatic site may be
      characterized by long-term failure. Additionally, the use of immunosuppressive
      agents such as prednisone may adversely affect long-term graft function. In this
      study, we examined the long-term outcome of intrahepatic canine islet autografts
      and compared this with results obtained in animals treated with a short-term
      course of steroids or steroids plus insulin. Islets were isolated using the
      automated method and were purified on discontinuous Euro-Collins Ficoll gradients
      (densities: 1.108, 1.096, 1.037). Prednisone-treated dogs were hyperglycemic
      during treatment but returned to normoglycemia after steroid withdrawal. Control
      and insulin-treated animals were normoglycemic following autotransplant, with no
      difference in plasma glucose levels between controls and the insulin-treated
      animals. All control dogs became diabetic at 11, 14, 17, and 19 months following
      islet autograft. Prednisone-treated dogs had more rapid onset of diabetes at 7,
      11, and 12 months following ITx. Prednisone-treated dogs given insulin became
      hyperglycemic at 10, 14, 18, and 19 months post ITx. Graft failure was preceded
      by a decline in IVGTT Kg values and diminished insulin secretion. At the time of
      graft failure islets showed no lymphocytic infiltration and islets stained
      positive for glucagon but few insulin-containing cells were seen. Thus, even when
      an initially adequate B cell mass was transplanted, the intrahepatic site was
      characterized by long-term canine autograft failure. A short course of prednisone
      accelerated the time to graft failure and insulin treatment reversed this
      acceleration.

PMID- 8310506
TI  - The capacity of dog lung to release prostaglandin I2 as a biochemical parameter
      for evaluating lung damage during preservation.
AB  - The release of prostaglandin I2 (PGI2) from the vasculature is thought to reflect
      damage to the vessels. Basal and bradykinin (BK)-stimulated release of PGI2 from
      isolated dog lungs after 6-hr preservation were investigated to evaluate lung
      damage after preservation. Maximal PGI2 release induced by BK decreased
      significantly after preservation at 24 degrees C (room temperature), but not
      after hypothermic preservation at 4 degrees C, although basal PGI2 release
      without BK stimulation did not change in either group of lungs after
      preservation. The function of allotransplanted lungs assessed by arterial oxygen
      tension was impaired by preservation at room temperature but not by hypothermic
      preservation. No differences were observed by light microscopy in either group in
      the pulmonary tissues, including the pulmonary artery, after preservation. In
      summary, damage to the lung after preservation may be reflected by the maximal
      PGI2 release from the lung after BK infusion. Therefore the maximal PGI2
      releasing capacity induced by BK may be a useful biochemical parameter for
      estimating the viability of preserved lungs.

PMID- 8310507
TI  - Prevention of acute rejection episodes with an anti-interleukin 2 receptor
      monoclonal antibody. I. Results after combined pancreas and kidney
      transplantation.
AB  - A prospective, randomized trial was conducted to evaluate the short-term and long
      term effects of induction immunosuppression with the rat IgG 2a monoclonal
      antibody 33B3.1, directed against the human alpha chain of the interleukin 2
      receptor, following primary, cadaveric, combined pancreas and kidney
      transplantation. Forty patients were randomly assigned to receive 10 mg/day of
      33B3.1 (n = 20) or 1.5 mg/kg/day of rabbit antithymocyte globulin (n = 20) for
      the first 10 postoperative days. Azathioprine, low-dose corticosteroids, and
      cyclosporine were given in association with either 33B3.1 or ATG. All 40 patients
      received the entire 10-day bioreagent course and no episode of rejection was
      observed during this period. Although the incidence of rejection did not
      significantly differ within the first, second, and third postoperative months
      (ten 33B3.1 and 6 ATG patients experienced, respectively, 10 and 6 rejection
      episodes within the first 3 months), the total number of 33B3.1 patients
      experiencing rejection throughout the follow-up was significantly higher than
      that of ATG (13 versus 6; P < 0.02). Immunological graft failure accounted for 2
      pancreas and 2 kidney losses in the 33B3.1 group versus 1 in the ATG one (P =
      ns). The total number of infectious episodes was similar in both groups (21
      versus 23). Two malignancies were observed in the ATG group (1 responsible for
      patient's death). One 33B3.1 patient died because of infectious pneumonia and 3
      ATG patients died because of 2 cardiovascular diseases and 1 cancer. All patients
      had functioning grafts at the time of death. The 3-month and 36-month patient,
      pancreas, and kidney actuarial survival rates were, respectively, 100, 65, and
      100%, and 95, 50, and 82% in the 33B3.1 group and 95, 80, and 90%, and 80, 70,
      and 80% in the ATG one (P = ns). These data suggest that, although a
      significantly higher rejection episode incidence was observed in patients treated
      with 33B3.1 monoclonal antibody as compared with ATG, similar long-term results
      can be obtained following primary cadaveric combined pancreas/kidney
      transplantation.

PMID- 8310509
TI  - Histological findings in early routine biopsies of stable renal allograft
      recipients.
AB  - Seventy renal allograft biopsies were done in 31 patients, routinely at 1, 2, and
      3 months posttransplant, and as clinically indicated, using an automated biopsy
      "gun." The histological diagnosis was made according to the Banff schema, which
      emphasizes tubulitis and vascular inflammation over mononuclear cell
      infiltration. Fifty-three biopsies satisfied histological inclusion criteria.
      Twenty-nine biopsies were obtained from stable patients, defined as those in whom
      serum creatinine had changed < 10% in 2 weeks, and in whom immunosuppression
      (cyclosporine, azathioprine, and prednisone) had not been increased in that
      interval. Of these biopsies, 30% (9/29) showed rejection, which could not have
      been predicted from pretransplant (HLA mismatch, panel-reactive antibody titer)
      or posttransplant (cyclosporine and serum interleukin 2 receptor levels)
      variables. The significance of these early subclinical rejection episodes is
      unknown, and their effects on long-term graft histology and function are being
      examined in a controlled study.

PMID- 8310508
TI  - Prevention of acute rejection episodes with an anti-interleukin 2 receptor
      monoclonal antibody. II. Results after a second kidney transplantation.
AB  - The focus of progress in transplantation immunosuppression is to achieve more
      specific immunosuppression with monoclonal antibodies. We have already shown that
      the efficacy of 33B3.1, a rat monoclonal Ig2A directed against the human IL-2
      receptor, was similar to that of rabbit antithymocyte globulin in the prevention
      of acute rejection in first kidney transplants. A similar comparative analysis
      has been made in 40-sec renal transplants. ATG (1 mg/kg/day) or 33B3.1 (10
      mg/day) was administered during the first 10 days postgrafting in association
      with corticosteroids and azathioprine. Cyclosporine was introduced on day 9 and
      azathioprine/CsA constituted the patient's maintenance treatment after day 45.
      Rejection treatment consisted of equine antilymphocyte globulin in both cases and
      of steroid boluses when patients were under Cyclosporine. One patient in each
      group died. Graft survival was 90%, 85%, and 79% in the ATG group (n = 20) and
      100%, 89%, and 89% in the 33B3.1 group (n = 20) at 3, 12, and 24 months,
      respectively. Of the ATG group patients, 45% and 40% in the 33B3.1 group had at
      least one rejection episode, half the episodes in the MoAb cohort occurring under
      33B3.1, vs. none in the ATG group. Transplant function was similar in both
      groups. Viral infections appeared to be more frequent with ATG (60%) than with
      33B3.1 (12%), with CMV accounting for half of these in the ATG group, and none in
      the MoAb group. Tolerance of both agents was good. Of the 33B3.1 recipients, 70%
      developed anti-33B3.1 antibodies. From these data, we conclude that this anti-IL
      2 receptor MoAb seems less effective than rabbit ATG as induction treatment in
      second kidney transplant patients.

PMID- 8310510
TI  - The beneficial effect of human recombinant superoxide dismutase on acute and
      chronic rejection events in recipients of cadaveric renal transplants.
AB  - In a prospective randomized double-blind placebo-controlled trial, the effect of
      rh-SOD, given in a dose of 200 mg intravenously during surgery to cyclosporine
      treated recipients of cadaveric renal allografts, on both acute and chronic
      rejection events as well as patient and graft survival was investigated by
      analyzing the patients' charts retrospectively. The results obtained show that rh
      SOD exerts a beneficial effect on acute rejection events as indicated by a
      significant reduction of (1) first acute rejection episodes from 33.3% in
      controls to 18.5%, as well as (2) early irreversible acute rejection from 12.5%
      in controls to 3.7%. With regard to long-term results, there was a significant
      improvement of the actual 4-year graft survival rate in rh-SOD-treated patients
      to 74% (with a projected half-life of 15 years) compared with 52% in controls
      (with an extrapolated half-life of 5 years). The beneficial effect of rh-SOD
      observed in this trial is not fully understood, although one can assume that the
      effect is related to its antioxidant action on ischemia/reperfusion injury of the
      renal allograft, thereby potentially reducing the immunogenicity of the graft. In
      addition and in accordance with the "response-to-injury hypothesis" in the
      pathogenesis of general atherosclerosis, rh-SOD has the potential to mitigate
      free radical-mediated reperfusion injury-induced acute endothelial cell damage
      that potentially may contribute to the process of chronic obliterative rejection
      arteriosclerosis.

PMID- 8310511
TI  - Risk factors for survival following combined heart-lung transplantation. The
      first 100 patients.
AB  - As the numbers of heart and lung transplant recipients have increased it has
      become possible to identify major risk factors for early (within 3 months) and
      later (after 3 months) death after this procedure. For 100 patients receiving
      organs between April 1984 and February 1991, and followed up until February 1992,
      patient characteristics, operative details, and early morbidity were assessed for
      their effects on early and later deaths. Recipient age, sex, and preoperative
      diagnosis did not have a significant effect on early (within 3 months) or later
      death. Positive cytomegalovirus antibody status of donor or recipient conferred
      greater risk of death within 90 days (odds ratio [OR] = 3.24, P = 0.06). Greater
      than 2 L blood in the first 24 hr after operation (OR = 6.00, P = 0.05), and
      ventilation for greater than 24 hr (OR = 4.87, P = 0.006) were significant
      prognostic indicators of early death. After the first 3 months, the main risk
      factor for death was rejection in the first 3 months (OR = 1.38 per episode, P =
      0.008). Early infection in general and CMV infection in particular were
      associated with a small increase in risk. This study confirms the importance of
      matching donor and recipient for CMV and shows that difficulties during
      operation, reflected in postoperative bleeding and ventilation times increased
      the chance of early death. Later death was associated with early acute rejection.
      A detrimental effect of infection, including CMV infection, either does not
      exist, or is too small to be detected in a study of this size.

PMID- 8310512
TI  - Orthotopic liver transplantation in children with chronic liver disease and
      severe hypoxemia.
AB  - Liver transplantation has been considered until recently as an absolute
      contraindication in hypoxemic patients. We report our experience in nine patients
      who had orthotopic liver transplantation between June 1986 and June 1992. These
      patients had cirrhosis-related hypoxemia with intrapulmonary shunting (IPS). The
      arterial oxygen pressure (PaO2) on room air ranged from 47 to 78 mmHg. OLT
      resulted in resolution of hypoxemia and closure of IPS in five patients whose
      hypoxemia was higher than 60 mmHg, and in death for the remaining four patients
      who had severe hypoxemia (PaO2 < 60 mmHg). We conclude that hypoxemia is no
      longer a contraindication to liver transplantation. Patients having PaO2 levels
      higher than 60 mmHg should have OLT as soon as possible before reaching lower
      levels of PaO2, and combined lung-liver transplantation or heart-lung-liver
      transplantation should be discussed in patients with severe hypoxemia (PaO2 < 60
      mmHg).

PMID- 8310513
TI  - The use of percutaneous transluminal angioplasty in hepatic artery stenosis after
      transplantation.
AB  - Graft ischemia following liver transplantation is associated with a high
      incidence of morbidity and mortality. The present report concerns a group of
      seven patients in whom an anastomotic stenosis of the hepatic artery was
      identified. Three patients had unexplained allograft dysfunction at a median time
      of 28 days (range 13-64 days), and 3 had a biliary leak at a median time of 42
      days after liver transplantation (range 35-270 days). In one patient the stenosis
      was diagnosed by routine Doppler ultrasound one week after transplant. Management
      was by percutaneous transluminal angioplasty at a median time of 35 days (range
      13-270 days) after transplantation. After angioplasty there was a marked
      improvement in clinical appearance, liver function, and liver histology in 5 of
      the 7 patients. Those patients who had a biliary leak subsequently developed
      strictures that eventually required biliary tract reconstruction
      (hepaticojejunostomy) in two and retransplantation in one. Percutaneous
      transluminal angioplasty is an effective way of improving arterial blood flow in
      cases of anastomotic stenosis, reducing the likelihood of complete occlusion by
      thrombosis. If recognized early and treated promptly ischemic changes in the
      graft can resolve and the development of biliary strictures may be avoided.

PMID- 8310514
TI  - Recognition and rapid diagnosis of upper gastrointestinal cytomegalovirus
      infection in marrow transplant recipients. A comparison of seven virologic
      methods.
AB  - This is a retrospective study of 54 consecutive upper gastrointestinal
      endoscopies in marrow graft recipients performed to determine the incidence and
      distribution of CMV infection in symptomatic patients and to compare the
      sensitivities of 7 CMV detection techniques. At each endoscopy, 3 biopsies were
      obtained from the esophagus, stomach, and duodenum. Each of the 3 biopsies was
      assayed for CMV by different techniques. Enteric CMV was identified by one or
      more techniques in 52 of 486 (11%) biopsies from 14 infected patients. All
      patients infected with CMV initially had nausea and vomiting. In 13 of these
      patients, there was esophageal CMV, often associated with stomach (10 patients)
      and duodenal (7 patients) involvement. CMV infection of the esophagus was never
      identified cytologically in esophageal imprints or histologically,
      immunohistologically, or by DNA hybridization in esophageal epithelial cells. The
      most sensitive diagnostic methods were conventional and centrifugation cultures,
      which each identified CMV in 17 of the 30 (57%) organs positive by any technique.
      Indirect fluorescent antibody (IFA) staining for a late CMV antigen detected 53%,
      followed by in situ DNA hybridization (40%), IFA and immunoperoxidase (IP)
      staining for an early CMV antigen (37% and 43%), and routine histology (30%).
      Although no single detection technique is completely adequate for the rapid
      identification of CMV in small endoscopic biopsies, centrifugation culture is the
      method of choice, with supplementary immunohistology and in situ hybridization of
      archival tissue if needed.

PMID- 8310516
TI  - Hyperacute xenograft rejection in the swine-to-human donor-recipient combination.
      In vitro analysis of complement activation.
AB  - Complement activation is central to the rejection of discordant xenografts. In
      order to assess the respective roles of direct and alternative pathways, an in
      vitro model of hyperacute rejection in the swine-to-human donor-recipient
      combination was designed, using a complement-dependent cytotoxicity test with
      swine endothelial cells in culture as targets, and fresh human serum as the
      source of xenogeneic antibodies and complement. The cytotoxic activity of the
      sera was evaluated by a colorimetric assay using (3-[4,5-dimethyldiazol-2-yl]-2,5
      diphenyl tetrazolium bromide (MTT). Pure human serum lysed 58 +/- 5% of swine
      endothelial cells. Selective inhibition of the direct pathway by adding EGTA to
      the serum reduced cytolysis to 51 +/- 2% (P < 0.01 versus normal serum).
      Similarly, when using C1q-deficient human sera, only 37 +/- 7% of swine
      endothelial cells were killed (P < 0.001 versus normal serum). When the
      alternative pathway was selectively inhibited by heating for 20 min at 50 degrees
      C, the lytic activity of human serum dropped to 42 +/- 5% (P < 0.001 versus
      normal serum). Factor B-deficient human serum could only lyse 42 +/- 10% of
      porcine endothelial cells (P < 0.001 versus normal serum). Syngeneic normal swine
      serum and heat-inactivated serum were not cytotoxic. Mixing serum with deficient
      direct pathway and serum with deficient alternative pathway restored the
      cytotoxicity to normal levels. Similarly, the cytotoxic activity of deficient
      serum supplemented with purified C1q or factor B at physiological concentrations
      reached that of normal human serum. In this model of in vitro hyperacute
      rejection, both pathways of complement activation are involved, suggesting that
      regimens designed to inhibit hyperacute rejection of swine xenografts into humans
      should take into account the dual activation of complement in this donor
      recipient combination.

PMID- 8310515
TI  - Tolerance to discordant xenografts. I. Sharing of human natural antibody
      determinants on miniature swine bone marrow cells and endothelial cells.
AB  - Xenotransplantation could potentially overcome the organ shortage that currently
      limits the field of transplantation. Because of their breeding characteristics as
      well as their size and physiologic similarities to humans, we have chosen
      miniature swine as possible xenograft donors, and are currently attempting to
      develop a means of using mixed xenogeneic chimerism as an approach to tolerance
      induction in swine-to-primate species combinations. One major barrier to organ
      grafting from pig to man is the presence in human serum of preformed natural
      antibodies (NAb) reacting with antigens expressed on porcine endothelial cells
      and causing hyperacute rejection. Previous experiments performed in our
      laboratory have shown that both humoral and cellular tolerance can be induced in
      a concordant xenogeneic species combination (rat-->mouse) using donor bone marrow
      infusion following conditioning with a nonmyeloablative regimen. Induction of
      chimerism in these animals was associated with a marked reduction in the level of
      IgM natural antibodies that recognize rat bone marrow cells. A similar approach
      could also lead to humoral and cellular tolerance induction in the swine-->human
      species combination, permitting transplantation of vascularized organs from the
      swine donor. To determine the potential of bone marrow transplantation to induce
      a state of "natural antibody tolerance," it was essential to determine whether or
      not all human NAb target antigens expressed on swine EC are also expressed on
      cells derived from swine bone marrow. We have addressed this question by
      evaluating the ability of various swine bone marrow-derived cells to absorb human
      IgM and IgG NAb that bind to swine EC. Our results demonstrate that swine bone
      marrow cells and their progeny can absorb almost all IgM NAb that bind to swine
      EC, as detected by flow cytometric and ELISA assays. Specificity of absorption
      was demonstrated, as total serum IgM levels declined only minimally after
      absorption on swine BMC and to an extent comparable to that observed following
      absorption with human cells, which did not deplete swine EC-binding NAb. Human
      IgG binding to swine EC was also completely absorbed by swine BMC. These results
      suggest that a state of "NAb tolerance" could be induced by successful swine
      marrow engraftment in man. Furthermore, swine PBL, platelets, and EC were able to
      absorb most IgM NAb that bound to swine BMC, suggesting that absorption using
      antigen from any of these tissues might facilitate marrow engraftment, and hence
      tolerance induction, in this species combination.

PMID- 8310517
TI  - Induction of specific unresponsiveness to cardiac allografts by short-term
      administration of anti-T cell receptor alpha beta antibody.
AB  - Organ graft rejection is a T cell-dependent process in which activation of
      alloreactive T cells via the T cell receptor/CD3 complex is a critical step.
      Although treatment with anti-CD3 has been shown to prevent and reverse allograft
      rejection, there is little information available regarding the effects of
      immunotherapy using anti-TCR alpha beta mAb for rejection. In the present study,
      short-term preoperative treatment of rats with a mAb against alpha beta TCR (R73)
      completely prevented the rejection of cardiac allografts. These rats accepted
      second cardiac allografts from the same donor strain, but not from a third-party
      strain, without additional treatment. In mixed lymphocyte cultures, T cells from
      rats that had received cardiac grafts did not respond to donor-strain heart
      cells, but did respond to donor-strain spleen cells and third-party heart cells.
      These findings suggest that specific unresponsiveness to cardiac tissue was
      induced in R73-treated rats. Such unresponsiveness was induced only when rats
      were pretreated with the mAb and subsequently received a transplant. It is likely
      that administration of a small dose of R73 induced transient immunomodulation of
      TCR molecules, resulting in unresponsiveness to a subsequent cardiac allograft.
      Immunotherapy with mAb against TCR alpha beta is very effective, without apparent
      side effects, and may provide a new method for preventing graft rejection.

PMID- 8310518
TI  - The contribution of endothelial cells to hyperacute rejection in xenogeneic
      perfused working hearts.
AB  - The mechanisms leading to the hyperacute rejection of a vascularized xenograft
      are still incompletely understood. The first stage of the rejection process is
      when blood of the recipient comes into contact with the endothelium of the
      xenograft. A working heart model was used to examine endothelium-related
      processes and their impact on organ function. Pig hearts were perfused with
      porcine (autologous) or human (xenogeneic) blood. Cardiac function was evaluated
      by calculating the stroke work index, arteriovenous oxygen, coronary flow, and
      resistance. PgF1a as a marker of endothelial activation, its antagonist TXB2, and
      myoglobin reflecting myocardial damage were measured in the hemoperfusate. H&E
      and PAS staining and immunohistological demonstration of factor VIII-related
      antigen was performed. Xenogeneic perfused porcine hearts showed significantly
      less stroke work, a higher arteriovenous oxygen difference, and an increased
      coronary resistance. Factor VIII-related antigen could not be demonstrated
      immunohistologically on the endothelium after xenogeneic perfusion. PgF1a levels
      were significantly higher in the xenogeneic hemoperfusate, indicating endothelial
      cell activation. The concentration of myoglobin in the hemoperfusate remained
      within normal values and was similar during autologous and xenogeneic perfusion.
      Therefore endothelium-related processes are likely to affect the coronary
      circulation--thus being one mechanism leading to diminished cardiac performance
      during hyperacute rejection.

PMID- 8310519
TI  - Evidence that the antibiotic ciprofloxacin counteracts cyclosporine-dependent
      suppression of cytokine production.
AB  - The fluoroquinolone antibiotic ciprofloxacin (cipro) has been reported to
      upregulate interleukin 2 and interferon-gamma production in lectin-stimulated
      lymphocytes. The aim of this study was to elucidate whether cipro and the
      immunosuppressive agent CsA have antagonistic action on cytokine synthesis.
      Accumulation of IL-2 and IFN-gamma protein and mRNA were analyzed in polyclonally
      (PHA or Con A) or alloantigen-stimulated human peripheral blood lymphocytes. CsA
      added simultaneously with PHA partially blocked cytokine synthesis. The present
      study also shows that cipro supplemented with CsA and PHA resulted in significant
      higher concentrations of IL-2 (up to 60 times) and IFN-gamma (4.3 times) as
      compared with PHA and CsA alone. Similar results were obtained with primary mixed
      lymphocyte reactions. In parallel, a greater amount of IL-2 and IFN-gamma mRNA
      was observed in lymphocytes incubated with both cipro and CsA as compared with
      CsA alone. Our results reveal that CsA-dependent inhibition of both IL-2 and IFN
      gamma expression is counteracted by high concentrations of cipro. These findings
      may be of importance in clinical transplantation.

PMID- 8310520
TI  - The role of tumor necrosis factor and interferon gamma in graft-versus-host
      disease and related immunodeficiency.
AB  - The role of TNF in the expression of GVHD and GVHD-related immunodeficiency was
      studied in a well-established murine GVHD model of bone marrow transplantation
      across minor histocompatibility barriers (B10.BR-->GBA/J) both in vitro and in
      vivo. Splenocytes from animals with GVHD profoundly inhibited the proliferation
      of normal spleen cells in response to a wide range of stimuli in an MHC
      nonrestricted fashion. Neutralizing mAbs to TNF reversed the ability of
      splenocytes from animals with GVHD to suppress the proliferation of normal
      splenocytes stimulated by the mitogen concanavalin A. Addition of rTNF enhanced
      the degree of suppression. This reversal was similar to that previously reported
      for IFN gamma and leucine methyl ester treatment of the GVHD populations. All
      three components are necessary for suppression to occur because addition of rTNF
      to cultures in which suppression had been reversed by anti-IFN gamma or leucine
      methyl ester treatment did not reconstitute suppression. Neutralization of
      endogenous TNF production in vivo resulted in an amelioration of clinical GVHD,
      but neutralization of endogenous IFN gamma resulted in a more severe course.
      However, in vivo neutralization of either TNF or IFN gamma post-BMT resulted in a
      decreased ability of splenocytes from animals with GVHD to suppress mitogen
      responses but did not affect the generation of the suppressor cell population.
      These findings support multiple roles for TNF and IFN gamma in the
      pathophysiology of GVHD, including terminal cellular differentiation and/or
      regulation of effector cell function.

PMID- 8310521
TI  - The possibility of restoration of human pancreas function during preservation by
      the two-layer (University of Wisconsin solution/perfluorochemical) method
      following normothermic ischemia.

PMID- 8310522
TI  - The effects of various routes of administration of monoclonal anti-T cell
      antibodies for prevention of the graft-versus-host reaction following small bowel
      transplantation.

PMID- 8310523
TI  - The effect of machine perfusion preservation versus cold storage on the function
      of kidneys from non-heart-beating donors.